l{K}, with
l{K} the spin screening length. We establish a proportionality between the weight
of the Kondo resonance and l{K} as a function of L. This suggests a spectroscopic
way of detecting the Kondo cloud.
PMID- 17026061
TI - Effect of strain on the carrier mobility in heavily doped p-type Si.
AB - We present an experiment that gives insight into the origin of the dependence of
the hole mobility (mu) on the dopant species in heavily doped p-type Si under low
electrical field. The Hall carrier concentration and mobility were measured in Si
coimplanted with B and Ga in the 0.1-2 x 10{20} cm{-3} concentration range. The
strain induced by substitutional dopants, detected by high resolution x-ray
diffraction, was varied by changing the relative B and Ga concentration. The
effect of strain on mobility was disentangled and a linear relationship between
1/mu and the perpendicular strain was found.
PMID- 17026062
TI - Magnetic fullerenes inside single-wall carbon nanotubes.
AB - C(59)N magnetic fullerenes were formed inside single-wall carbon nanotubes by
vacuum annealing functionalized C(59)N molecules encapsulated inside the tubes. A
hindered, anisotropic rotation of C(59)N was deduced from the temperature
dependence of the electron spin resonance spectra near room temperature.
Shortening of the spin-lattice relaxation time T(1) of C(59)N indicates a
reversible charge transfer toward the host nanotubes above approximately 350 K.
Bound C(59)N-C(60) heterodimers are formed at lower temperatures when C(60) is
coencapsulated with the functionalized C(59)N. In the 10-300 K range, T(1) of the
heterodimer shows a relaxation dominated by the conduction electrons on the
nanotubes.
PMID- 17026063
TI - Magnetic-field enhancement of superconductivity in ultranarrow wires.
AB - We study the effect of an applied magnetic field on sub-10-nm wide MoGe and Nb
superconducting wires. We find that magnetic fields can enhance the critical
supercurrent at low temperatures, and do so more strongly for narrower wires. We
conjecture that magnetic moments are present, but their pair-breaking effect,
active at lower magnetic fields, is suppressed by higher fields. The
corresponding microscopic theory, which we have developed, quantitatively
explains all experimental observations, and suggests that magnetic moments have
formed on the wire surfaces.
PMID- 17026064
TI - Symmetric and asymmetric vortex-antivortex molecules in a fourfold
superconducting geometry.
AB - In submicron superconducting squares in a homogeneous magnetic field, Ginzburg
Landau theory may admit solutions of the vortex-antivortex type, conforming to
the symmetry of the sample [L. F. Chibotaru, Nature (London) 408, 833
(2000)10.1038/35048521]. Here we show that these fascinating, but never
experimentally observed states, can be enforced by artificial fourfold pinning,
with their diagnostic features enhanced by orders of magnitude. The second-order
nucleation of vortex-antivortex molecules can be driven by either temperature or
an applied magnetic field, with stable asymmetric vortex-antivortex equilibria
found on its path.
PMID- 17026065
TI - Phase textures induced by dc-current pair breaking in weakly coupled multilayer
structures and two-gap superconductors.
AB - We predict the current-induced formation of equilibrium phase textures for a
multicomponent superconducting order parameter. Using the two-component Ginzburg
Landau and Usadel equations, we show that, for weakly coupled comoving
superconducting condensates, the dc current I first causes the breakdown of the
phase-locked state at I>I{c1} followed by the formation of intrinsic phase
textures well below the depairing current I{d}. These phase textures can manifest
themselves in multilayer structures, atomic Bose condensate mixtures in optical
lattices, and two-gap superconductors, particularly MgB(2), where they can result
in oscillating and resistive switching effects.
PMID- 17026066
TI - Critical behavior of Griffiths ferromagnets.
AB - From a heuristic calculation of the leading order essential singularity in the
distribution of Yang-Lee zeroes, we obtain new scaling relations near the
ferromagnetic-Griffiths transition, including the prediction of a discontinuity
on the analogue of the critical isotherm. We show that experimental data for the
magnetization and heat capacity of La(0.7)Ca(0.3)MnO(3) are consistent with these
predictions, thus supporting its identification as a Griffiths ferromagnet.
PMID- 17026067
TI - Dynamics of a pinned magnetic vortex.
AB - We observe the dynamics of a single magnetic vortex pinned by a defect in a
ferromagnetic film. At low excitation amplitudes, the vortex core gyrates about
its equilibrium position with a frequency that is characteristic of a single
pinning site. At high amplitudes, the frequency of gyration is determined by the
magnetostatic energy of the entire vortex, which is confined in a micron-scale
disk. We observe a sharp transition between these two amplitude regimes that is
due to depinning of the vortex core from a local defect. The distribution of
pinning sites is determined by mapping fluctuations in the frequency as the
vortex core is displaced by a static in-plane magnetic field.
PMID- 17026068
TI - Determination of the antiferroquadrupolar order parameters in UPd(3).
AB - By combining accurate heat capacity and x-ray resonant scattering results we have
resolved the long standing question regarding the nature of the quadrupolar
ordered phases in UPd(3). The order parameter of the highest temperature
quadrupolar phase has been uniquely determined to be antiphase Q{zx} in contrast
to the previous conjecture of Q{x{2}-y{2}}. The azimuthal dependence of the x-ray
scattering intensity from the quadrupolar superlattice reflections indicates that
the lower temperature phases are described by a superposition of order
parameters. The heat capacity features associated with each of the phase
transitions characterize their order, which imposes restrictions on the matrix
elements of the quadrupolar operators.
PMID- 17026069
TI - Quantum spin glass and the dipolar interaction.
AB - Anisotropic dipolar systems are considered. Such systems in an external magnetic
field are expected to be a good experimental realization of the transverse field
Ising model. With random interactions, this model yields a spin glass to
paramagnet phase transition as a function of the transverse field. We show that
the off-diagonal dipolar interaction, although effectively reduced, induces a
finite correlation length and thus destroys the spin-glass order at any finite
transverse field. We thus explain the behavior of the nonlinear susceptibility in
the experiments on LiHo(x)Y(1-x)F(4), and argue that a crossover to the
paramagnetic phase, and not quantum criticality, is observed.
PMID- 17026070
TI - Opposite spin asymmetry of elastic and inelastic scattering of nonequilibrium
holes injected into a ferromagnet.
AB - The spin asymmetry of elastic and inelastic scattering of nonequilibrium holes
injected into Co thin films is examined using a p-type magnetic tunnel
transistor. Spin-dependent transmission yields a positive or negative
magnetocurrent depending on Co thickness and hole energy. Up to a critical
thickness of about 3 nm, (quasi)elastic scattering dominates with a short
attenuation length (<1 nm) and preferential attenuation of holes in the majority
spin bands, consistent with spin-wave emission. At a larger Co thickness,
inelastic scattering dominates with a larger attenuation length ( approximately 4
nm) and opposite spin asymmetry.
PMID- 17026071
TI - Electron spin resonance of proton-irradiated graphite.
AB - In the case of colossal magnetoresistance in the perovskite manganites, "double
exchange" mediated by the itinerant spins is believed to play a key role in the
ferromagnetism. In contrast, the conventional "Heisenberg" interaction, i.e.,
direct (unmediated) interaction between the localized spins produced by the
proton irradiation, is identified as the origin of proton irradiation-induced
ferromagnetism in graphite.
PMID- 17026072
TI - Easily coupled whispering gallery plasmons in dielectric nanospheres embedded in
gold films.
AB - A new self-aligned robust method for coupling to whispering gallery modes (WGMs)
of submicron microspheres utilizes their periodic arrangement without relying on
nanopositioned external coupling devices. The microspheres are embedded in a
nanostructured gold surface supporting delocalized plasmonic crystal modes that
mediate the coupling, and can be tuned by the geometry. Detailed measurements of
the angle- and orientation-dependent reflectivity reveal localized plasmonic WGMs
whose energies scale with sphere diameter and agree closely with Mie
calculations. Coupling between these plasmonic WGMs leads to mode splitting and
the formation of plasmonic minibands of a controllable bandwidth.
PMID- 17026073
TI - Ab initio calculation of optical spectra of liquids: many-body effects in the
electronic excitations of water.
AB - We present ab initio calculations of the excited state properties of liquid water
in the framework of many-body Green's function formalism. Snapshots taken from
molecular dynamics simulations are used as input geometries to calculate
electronic and optical spectra, and the results are averaged over the different
configurations. The optical absorption spectra with the inclusion of excitonic
effects are calculated by solving the Bethe-Salpeter equation. The insensitivity
of screening effects to a particular configuration make these calculations
feasible. The resulting spectra, which are strongly modified by many-body
effects, are in good agreement with experiments.
PMID- 17026074
TI - Origin of the relaxor state in Pb(B{x}B{1-x}{'})O(3) perovskites.
AB - Molecular dynamics simulations of first-principles-based effective Hamiltonians
for Pb(Sc{1/2}Nb{1/2})O(3) under hydrostatic pressure and for
Pb(Mg{1/3}Nb{2/3})O(3) at ambient pressure show clear evidence of a relaxor state
in both systems. The Burns temperature is identified as the temperature below
which dynamic nanoscale polar clusters form, pinned to regions of quenched
chemical short-range order. The effect of pressure in Pb(Sc{1/2}Nb{1/2})O(3)
demonstrates that the stability of the relaxor state depends on a delicate
balance between the energetics that stabilize normal ferroelectricity and the
average strength of random local fields which promote the relaxor state.
PMID- 17026075
TI - Water percolation governs polymorphic transitions and conductivity of DNA.
AB - We report on the first computer simulation studies of the percolation transition
of water at the surface of the DNA double helix. With increased hydration, the
ensemble of small clusters merges into a spanning water network via a quasi-two
dimensional percolation transition. This transition occurs strikingly close to
the hydration level where the B form of DNA becomes stable in experiment.
Formation of spanning water networks results in sigmoidlike acceleration of long
range ion transport in good agreement with experiment.
PMID- 17026076
TI - Critical role of gravity in filters.
AB - The efficiency of filters depends crucially on the mass of the particles one
wants to capture. Using analytical and numerical calculations we reveal a very
rich scenario of scaling laws relating this efficiency to particle size and
density and the velocity and viscosity of the carrying fluid. These are combined
in the dimensionless, so-called Stokes number St. In the case of horizontal flow
or neutrally buoyant particles, we find a critical number St{c} below which no
particles are trapped; i.e., the filter does not work. Above St{c} the capture
efficiency increases like the square root of (St-St{c}). Under the action of
gravity, the threshold abruptly vanishes and capture occurs at any Stokes number
increasing linearly in St. We discovered further scaling laws in the penetration
profile and as function of the porosity of the filter.
PMID- 17026077
TI - Shear-flow-induced unfolding of polymeric globules.
AB - The behavior of a single collapsed polymer under shear flow is examined using
hydrodynamic simulations and scaling arguments. Below a threshold shear rate
gamma[.]{*}, the chain remains collapsed and only deforms slightly, while above
gamma[.]{*} the globule exhibits unfolding/refolding cycles. Hydrodynamics are
crucial: In the free draining case, gamma[.]{*} scales with the globule radius R
as gamma[.]{*} approximately R{-1}, while in the presence of hydrodynamic
interactions gamma[.]{*} approximately R. Experiments on the globular von
Willebrand protein confirm the presence of an unfolding transition at a well
defined critical shear rate.
PMID- 17026078
TI - Tissue self-affinity and polarized light scattering in the born approximation: a
new model for precancer detection.
AB - Light scattered from biological tissues can exhibit an inverse power law spectral
component. We develop a model based on the Born approximation and von Karman
(self-affine) spatial correlation of submicron tissue refractive index to account
for this. The model is applied to light scattering spectra obtained from excised
esophagi of normal and carcinogen-treated rats. Power law exponents used to fit
dysplastic tissue site spectra are significantly smaller than those from normal
sites, indicating that changes in tissue self-affinity can serve as a potential
biomarker for precancer.
PMID- 17026079
TI - Efficiency of initiating cell adhesion in hydrodynamic flow.
AB - We theoretically investigate the efficiency of initial binding between a receptor
coated sphere and a ligand-coated wall in linear shear flow. The mean first
passage time for binding decreases monotonically with increasing shear rate.
Above a saturation threshold of the order of a few 100 receptor patches, the
binding efficiency is enhanced only weakly by increasing their number and size,
but strongly by increasing their height. This explains why white blood cells in
the blood flow adhere through receptor patches localized to the tips of
microvilli, and why malaria-infected red blood cells form elevated receptor
patches (knobs).
PMID- 17026080
TI - Lieb-Robinson bounds and the generation of correlations and topological quantum
order.
AB - The Lieb-Robinson bound states that local Hamiltonian evolution in
nonrelativistic quantum mechanical theories gives rise to the notion of an
effective light cone with exponentially decaying tails. We discuss several
consequences of this result in the context of quantum information theory. First,
we show that the information that leaks out to spacelike separated regions is
negligible and that there is a finite speed at which correlations and
entanglement can be distributed. Second, we discuss how these ideas can be used
to prove lower bounds on the time it takes to convert states without topological
quantum order to states with that property. Finally, we show that the rate at
which entropy can be created in a block of spins scales like the boundary of that
block.
PMID- 17026081
TI - Spectroscopy of ultracold atoms by periodic lattice modulations.
AB - We present a nonperturbative analysis of a new experimental technique for probing
ultracold bosons in an optical lattice by periodic lattice depth modulations.
This is done using the time-dependent density-matrix renormalization group
method. We find that sharp energy absorption peaks are not unique to the Mott
insulating phase at commensurate filling but also exist for superfluids at
incommensurate filling. For strong interactions, the peak structure provides an
experimental measure of the interaction strength. Moreover, the peak height of
the peaks at Planck's omega > or approximately 2U can be employed as a measure of
the incommensurability of the system.
PMID- 17026082
TI - E expansion for a Fermi gas at infinite scattering length.
AB - We show that there exists a systematic expansion around four spatial dimensions
for Fermi gas in the unitarity regime. We perform the calculations to leading and
next-to-leading orders in the expansion over E = 4-d, where d is the
dimensionality of space. We find the ratio of chemical potential and Fermi energy
to be mu/epsilon(F) =1/2 (E 3/2) + 1/16 (E 5/2) lnE -0.0246E (5/2) + ... and the
ratio of the gap in the fermion quasiparticle spectrum and the chemical potential
to be Delta/mu =2E(-1) - 0.691 + ... . The minimum of the fermion dispersion
curve is located at |p|=(2mepsilon(0))(1/2), where epsilon_(0)/mu=2+O(E).
Extrapolation to d=3 gives results consistent with Monte Carlo simulations.
PMID- 17026083
TI - Entanglement entropy of 2D conformal quantum critical points: hearing the shape
of a quantum drum.
AB - The entanglement entropy of a pure quantum state of a bipartite system A union or
logical sumB is defined as the von Neumann entropy of the reduced density matrix
obtained by tracing over one of the two parts. In one dimension, the entanglement
of critical ground states diverges logarithmically in the subsystem size, with a
universal coefficient that for conformally invariant critical points is related
to the central charge of the conformal field theory. We find that the
entanglement entropy of a standard class of z=2 conformal quantum critical points
in two spatial dimensions, in addition to a nonuniversal "area law" contribution
linear in the size of the AB boundary, generically has a universal
logarithmically divergent correction, which is completely determined by the
geometry of the partition and by the central charge of the field theory that
describes the critical wave function.
PMID- 17026084
TI - Measuring multipartite concurrence with a single factorizable observable.
AB - We show that, for any composite system with an arbitrary number of finite
dimensional subsystems, it is possible to directly measure the multipartite
concurrence of pure states by detecting only one single factorizable observable,
provided that two copies of the composite state are available. This result can be
immediately put into practice in trapped-ion and entangled-photon experiments.
PMID- 17026085
TI - State tomography of capacitively shunted phase qubits with high fidelity.
AB - We introduce a new design concept for superconducting phase quantum bits (qubits)
in which we explicitly separate the capacitive element from the Josephson tunnel
junction for improved qubit performance. The number of two-level systems that
couple to the qubit is thereby reduced by an order of magnitude and the
measurement fidelity improves to 90%. This improved design enables the first
demonstration of quantum state tomography with superconducting qubits using
single-shot measurements.
PMID- 17026086
TI - Asymptotic violation of Bell inequalities and distillability.
AB - A multipartite quantum state violates a Bell inequality asymptotically if, after
jointly processing by general local operations an arbitrarily large number of
copies of it, the result violates the inequality. In the bipartite case we show
that asymptotic violation of the Clauser-Horne-Shimony-Holt inequality is
equivalent to distillability. Hence, bound entangled states do not violate it. In
the multipartite case we consider the complete set of full-correlation Bell
inequalities with two dichotomic observables per site. We show that asymptotic
violation of any of these inequalities by a multipartite state implies that pure
state entanglement can be distilled from it, although the corresponding
distillation protocol may require that some of the parties join into several
groups. We also obtain the extreme points of the set of distributions generated
by measuring N quantum systems with two dichotomic observables per site.
PMID- 17026087
TI - Limitations of quantum simulation examined by simulating a pairing Hamiltonian
using nuclear magnetic resonance.
AB - Quantum simulation uses a well-known quantum system to predict the behavior of
another quantum system. Certain limitations in this technique arise, however,
when applied to specific problems, as we demonstrate with a theoretical and
experimental study of an algorithm proposed by Wu, Byrd, and Lidar [Phys. Rev.
Lett. 89, 057904 (2002).10.1103/PhysRevLett.89.057904] to find the low-lying
spectrum of a pairing Hamiltonian. While the number of elementary quantum gates
required scales polynomially with the size of the system, it increases inversely
to the desired error bound E. Making such simulations robust to decoherence using
fault tolerance requires an additional factor of approximately 1/E gates. These
constraints, along with the effects of control errors, are illustrated using a
three qubit NMR system.
PMID- 17026088
TI - Trapped ion quantum computation with transverse phonon modes.
AB - We propose a scheme to implement quantum gates on any pair of trapped ions
immersed in a large linear crystal, using interaction mediated by the transverse
phonon modes. Compared with the conventional approaches based on the longitudinal
phonon modes, this scheme is much less sensitive to ion heating and thermal
motion outside of the Lamb-Dicke limit thanks to the stronger confinement in the
transverse direction. The cost for such a gain is only a moderate increase of the
laser power to achieve the same gate speed. We also show how to realize arbitrary
speed quantum gates with transverse phonon modes based on simple shaping of the
laser pulses.
PMID- 17026089
TI - Statistical-temperature Monte Carlo and molecular dynamics algorithms.
AB - A simulation method is presented that achieves a flat energy distribution by
updating the statistical temperature instead of the density of states in Wang
Landau sampling. A novel molecular dynamics algorithm (STMD) applicable to
complex systems and a Monte Carlo algorithm are developed from this point of
view. Accelerated convergence for large energy bins, essential for large systems,
is demonstrated in tests on the Ising model, the Lennard-Jones fluid, and bead
models of proteins. STMD shows a superior ability to find local minima in
proteins and new global minima are found for the 55 bead AB model in two and
three dimensions. Calculations of the occupation probabilities of individual
protein inherent structures provide new insights into folding and misfolding.
PMID- 17026090
TI - Measurement of stochastic entropy production.
AB - Using fluorescence spectroscopy we directly measure entropy production of a
single two-level system realized experimentally as an optically driven defect
center in diamond. We exploit a recent suggestion to define entropy on the level
of a single stochastic trajectory [Seifert, Phys. Rev. Lett. 95, 040602
(2005)10.1103/PhysRevLett.95.040602]. Entropy production can then be split into
one of the system itself and one of the surrounding medium. We demonstrate that
the total entropy production obeys various exact relations for finite time
trajectories.
PMID- 17026091
TI - Exclusion processes with internal states.
AB - We introduce driven exclusion processes with internal states that serve as
generic transport models in various contexts, ranging from molecular or vehicular
traffic on parallel lanes to spintronics. The ensuing nonequilibrium steady
states are controllable by boundary as well as bulk rates. A striking
polarization phenomenon accompanied by domain wall motion and delocalization is
discovered within a mesoscopic scaling. We quantify this observation within an
analytic description providing exact phase diagrams. Our results are confirmed by
stochastic simulations.
PMID- 17026092
TI - High energy neutrino flashes from far-ultraviolet and x-ray flares in gamma-ray
bursts.
AB - The recent observations of bright optical and x-ray flares by the Swift satellite
suggest these are produced by the late activities of the central engine. We study
the neutrino emission from far-ultraviolet and x-ray flares under the late
internal shock model. We show that the efficiency of pion production in the
highest energy is comparable to or higher than the unity, and the contribution
from such neutrino flashes to a diffuse very high energy neutrino background can
be larger than that of prompt bursts if the total baryonic energy input into
flares is comparable to the radiated energy of prompt bursts. These signals may
be detected by IceCube and are very important because they have possibilities to
probe the nature of flares (the baryon loading, the photon field, the magnetic
field and so on).
PMID- 17026093
TI - Implications of direct dark matter constraints for minimal supersymmetric
standard model Higgs boson searches at the Tevatron.
AB - In regions of large tanbeta and small mAlpha, searches for heavy neutral minimal
supersymmetric standard model (MSSM) Higgs bosons at the Tevatron are promising.
At the same time, rates in direct dark matter experiments, such as CDMS, are
enhanced in the case of large tanbeta and small mAlpha. As a result, there is a
natural interplay between the heavy, neutral Higgs searches at the Tevatron and
the region of parameter space explored by CDMS. We show that if the lightest
neutralino makes up the dark matter of our universe, current limits from CDMS
strongly constrain the prospects of heavy, neutral MSSM Higgs discovery at the
Tevatron unless |mu| greater or approximately 400 GeV. The limits of CDMS
projected for 2007 will increase this constraint to |mu| greater or approximately
800 GeV. If CDMS does observe neutralinos in the near future, however, it will
make the discovery of Higgs bosons at the Tevatron far more likely.
PMID- 17026096
TI - Neutron and proton transverse emission ratio measurements and the density
dependence of the asymmetry term of the nuclear equation of state.
AB - Recent measurements of preequilibrium neutron and proton transverse emission from
(112,124)Sn+(112,124)Sn reactions at 50 MeV/A have been completed at the National
Superconducting Cyclotron Laboratory. Free nucleon transverse emission ratios are
compared to those of A=3 mirror nuclei. Comparisons are made to Boltzmann-Uehling
Uhlenbeck (BUU) transport calculations and conclusions concerning the density
dependence of the asymmetry term of the nuclear equation of state at subnuclear
densities are made. Comparison to BUU model predictions indicate a density
dependence of the asymmetry energy that is closer to a form in which the
asymmetry energy increases as the square root of the density for the density
region studied. A coalescent-invariant analysis is introduced as a means of
reducing suggested difficulties with cluster emission in total nucleon emission.
PMID- 17026097
TI - Quantum-control spectroscopy with exact state selectivity.
AB - A method of exact state-selective spectroscopy is introduced, based on quantum
control through four specific short laser pulses. The exact conditions for the
two pairs of ultrafast pulses are set by the feedback control for selective
excitation to one specific resonance state while the other state is destructively
interfered as the shadow pair, leading to a state-selective spectrum.
PMID- 17026098
TI - Quantum optics with surface plasmons.
AB - We describe a technique that enables strong, coherent coupling between individual
optical emitters and guided plasmon excitations in conducting nanostructures at
optical frequencies. We show that under realistic conditions optical emission can
be almost entirely directed into the plasmon modes. As an example, we describe an
application of this technique involving efficient generation of single photons on
demand, in which the plasmon is efficiently outcoupled to a dielectric waveguide.
PMID- 17026099
TI - Experimental investigation of core-valence double photoionization.
AB - Core-valence double photoionization has been observed in Ne atoms and N2
molecules using a magnetic-bottle time of flight spectrometer. The multielectron
coincidence data sets give complete information on the energy correlations
between all emitted electrons, which supports a detailed description of the core
valence double photoionization processes including direct spectroscopy of the
core-valence doubly ionized states, the final states populated by their Auger
decay and details of the dynamics of core-valence double photoionization for
selected states.
PMID- 17026100
TI - Squeezed-state purification with linear optics and feedforward.
AB - A scheme for optimal and deterministic linear optical purification of mixed
squeezed Gaussian states is proposed and experimentally demonstrated. The scheme
requires only linear optical elements and homodyne detectors, and allows the
balance between purification efficacy and squeezing degradation to be controlled.
One particular choice of parameters gave a tenfold reduction of the thermal noise
with a corresponding squeezing degradation of only 11%. We prove optimality of
the protocol, and show that it can be used to enhance the performance of quantum
informational protocols such as dense coding and entanglement generation.
PMID- 17026101
TI - Experimental verification of an optical vortex coronagraph.
AB - A coronagraph designed for high contrast imaging applications has been
experimentally tested using coherent laser light and a vortex mask of topological
charge m=2. Intensity contrast values of 95% were achieved in this first
verification of the scheme. Improvements for approaching the theoretical value of
100% are suggested.
PMID- 17026102
TI - Making tunnel barriers (including metals) transparent.
AB - The classical "brick wall," which may, according to quantum mechanics, leak via
tunneling, is here shown to be completely transparent when appropriate impedance
matching media are placed both in front of and behind the "wall." Optical
experiments involving beyond-critical-angle-tunnel barriers in the frustrated
total internal reflection scheme which mimic quantum mechanical systems provide
convincing proof of this remarkable effect. The same mechanism also allows vastly
enhanced transmission through unstructured thin metal films without the need for
surface wave excitation.
PMID- 17026095
TI - Dense-medium modifications to jet-induced hadron pair distributions in Au+Au
collisions at sqrt s NN=200 GeV.
AB - Azimuthal correlations of jet-induced high-p(T) charged hadron pairs are studied
at midrapidity in Au+Au collisions at sqrt[s(NN)]=200 GeV. The distribution of
jet-associated partner hadrons (1.0a1
(+/)(1260)pi(/+) with a1 (+/)(1260)-->pi(/+)pi(+/)pi(+/). The data sample
corresponds to 218 x 10(6) BB[over ] pairs produced in e+e- annihilation through
the Upsilon(4S) resonance. We measure the branching fraction Beta(B(0)-
>a1(+/)(1260)pi(/+))Beta(a1(+/)(1260)-->pi(/+)pi(+/)pi(+/)) = (16.6+/1.9+/1.5) x
10(-6), where the first error quoted is statistical and the second is systematic.
PMID- 17026113
TI - Universal features of terahertz absorption in disordered materials.
AB - Using an analytical theory, experimental terahertz time-domain spectroscopy data,
and numerical evidence, we demonstrate that the frequency dependence of the
absorption coupling coefficient between far-infrared photons and atomic
vibrations in disordered materials has the universal functional form,
C(omega)=A+Bomega(2), where the material-specific constants A and B are related
to the distributions of fluctuating charges obeying global and local charge
neutrality, respectively.
PMID- 17026114
TI - Efficient calculation of electron diffraction for the structural determination of
nanomaterials.
AB - A critical advance in the technique of low-energy electron diffraction is
presented and shown to enable determining detailed structures of nanomaterials,
based on experimental methods that already exist or have been proposed. Our new
cluster approach speeds up the computation to scale as n logn, rather than the
current n3 or n2, with n the number of atoms, for example. Applications are
illustrated for C60 molecules adsorbed on a Cu(111) surface, with and without
coadsorbed metal atoms, exhibiting sensitivity to important structural features
such as buckyball size and deformation.
PMID- 17026115
TI - Interplay between diffusive and displacive phase transformations: time
temperature-transformation diagrams and microstructures.
AB - Materials which can undergo extremely fast displacive transformations as well as
very slow diffusive transformations are studied using a Ginzburg-Landau
framework. This simple model captures the essential physics behind microstructure
formation and time-temperature-transformation diagrams in alloys such as steels.
It also predicts the formation of mixed microstructures by an interplay between
diffusive and displacive mechanisms. The intrinsic volume changes associated with
the transformations stabilize mixed microstructures such as martensite-retained
austenite (responsible for the existence of a martensite finish temperature) and
martensite-pearlite.
PMID- 17026116
TI - Fractional Stokes-Einstein and Debye-Stokes-Einstein relations in a network
forming liquid.
AB - We study the breakdown of the Stokes-Einstein (SE) and Debye-Stokes-Einstein
(DSE) relations for translational and rotational motion in a prototypical model
of a network-forming liquid, the ST2 model of water. We find that the emergence
of fractional SE and DSE relations at low temperature is ubiquitous in this
system, with exponents that vary little over a range of distinct physical
regimes. We also show that the same fractional SE relation is obeyed by both
mobile and immobile dynamical heterogeneities of the liquid.
PMID- 17026117
TI - Exactly quantized dynamics of classical incommensurate sliders.
AB - We report peculiar velocity quantization phenomena in the classical motion of an
idealized 1D solid lubricant, consisting of a harmonic chain interposed between
two periodic sliders. The ratio upsilon(c.m.)/upsilon(ext) of the chain center-of
mass velocity to the externally imposed relative velocity of the sliders stays
pinned to exact "plateau" values for wide ranges of parameters, such as slider
corrugation amplitudes, external velocity, chain stiffness, and dissipation, and
is strictly determined by the commensurability ratios alone. The phenomenon is
explained by one slider rigidly dragging the kinks that the chain forms with the
other slider. Possible consequences of these results for some real systems are
discussed.
PMID- 17026118
TI - Why N2 molecules with thermal energy abundantly dissociate on W(100) and not on
W(110).
AB - Low-energy N2 molecules easily dissociate on W(100) but not on W(110). In this
Letter, the six-dimensional potential energy surface for the dissociation of N2
molecules on W(110) has been determined by density functional calculations.
Results are compared to those of N2 dissociation on W(100). The difference in
reactivity between the two faces is shown to arise from the characteristics of
the potential energy surface far from the surface (>3 A) and not from the
properties of a precursor well or those of the final atomic adsorption sites.
PMID- 17026119
TI - Carbon monoxide dissociation on Rh nanopyramids.
AB - CO dissociation on rhomboidal faceted nanopyramids, produced on Rh(110) by fine
tuning of ion irradiation conditions, has been studied by high resolution core
level spectroscopy. We find that this morphology presents a large efficiency
towards CO dissociation, a process which is inhibited on flat (110) terraces. We
also measured the reactivity of nanostructures bound by different artificial step
distributions identifying the sites responsible for the molecular bond disruption
in the undercoordinated (n=6) edges running along the [11[over ]2] equivalent
directions, with CO sitting in on-top configuration.
PMID- 17026120
TI - Combinatorial search for optimal hydrogen-storage nanomaterials based on
polymers.
AB - We perform an extensive combinatorial search for optimal nanostructured hydrogen
storage materials among various metal-decorated polymers using first-principles
density-functional calculations. We take into account the zero-point vibration as
well as the pressure- and temperature-dependent adsorption-desorption probability
of hydrogen molecules. An optimal material we identify is Ti-decorated cis
polyacetylene with reversibly usable gravimetric and volumetric density of 7.6 wt
% and 63 kg/m(3), respectively, near ambient conditions. We also propose
"thermodynamically usable hydrogen capacity" as a criterion for comparing
different storage materials.
PMID- 17026121
TI - Quasiparticlelike peaks, kinks, and electron-phonon coupling at the (pi,0)
regions in the CMR oxide La2-2x Sr1+2x Mn2 O7.
AB - Using angle-resolved photoemission, we have observed sharp quasiparticlelike
peaks in the prototypical layered manganite La(2-2x)Sr(1+2x)Mn(2)O(7)
(x=0.36,0.38). We focus on the (pi,0) regions of k space and study their
electronic scattering rates and dispersion kinks, uncovering bilayer-split bands,
the critical energy scales, momentum scales, and strengths of the interactions
that renormalize the electrons. To identify these bosons, we measured phonon
dispersions in the energy range of the kink by inelastic neutron scattering,
finding a good match in both energy and momentum to the oxygen bond-stretching
phonons.
PMID- 17026122
TI - Synergistic polaron formation in the Hubbard-Holstein model at small doping.
AB - We study the effect of dynamical Holstein phonons on the physics of the Hubbard
model at small doping using the dynamical cluster approximation on a 2x2 cluster.
Nonlocal antiferromagnetic correlations are found to significantly enhance the
electron-phonon coupling, resulting in polaron formation for moderate coupling
strengths. At finite doping, the electron-phonon coupling is found to strongly
enhance the nonlocal spin correlations, indicating a synergistic interplay
between the electron-phonon coupling and antiferromagnetic correlations. Although
it enhances the pairing interaction, the electron-phonon coupling is found to
decrease the superconducting transition temperature, due to the reduction in the
quasiparticle fraction.
PMID- 17026123
TI - Resonant x-ray diffraction studies on the charge ordering in magnetite.
AB - Here we show that the low temperature phase of magnetite is associated with an
effective, although fractional, ordering of the charge. Evidence and a
quantitative evaluation of the atomic charges are achieved by using resonant x
ray diffraction (RXD) experiments whose results are further analyzed with the
help of ab initio calculations of the scattering factors involved. By confirming
the results obtained from x-ray crystallography we have shown that RXD is able to
probe quantitatively the electronic structure in very complex oxides, whose
importance covers a wide domain of applications.
PMID- 17026124
TI - Reversible tuning of the heavy-fermion ground state in CeCoIn5.
AB - Cadmium doping the heavy-fermion superconductor CeCoIn(5) at the percent level
acts as an electronic tuning agent, sensitively shifting the balance between
superconductivity and antiferromagnetism and opening new ambient-pressure phase
space in the study of heavy-fermion ground states.
PMID- 17026125
TI - Quantum thermal conductance of electrons in a one-dimensional wire.
AB - We use an electron thermometer to measure the temperature rise of approximately 2
x 10(5) electrons in a two-dimensional box, due to heat flow into the box through
a ballistic one-dimensional (1D) constriction. Using a simple model we deduce the
thermal conductance kappa(Vg) of the 1D constriction, which we compare to its
electrical conductance characteristics; for the first four 1D subbands the heat
carried by the electrons passing through the wire is proportional to its
electrical conductance G(Vg). In the vicinity of the 0.7 structure this
proportionality breaks down, and a plateau at the quantum of thermal conductance
pi(2)k(2/B)T/3h is observed.
PMID- 17026126
TI - Electron spin dynamics in a self-assembled semiconductor quantum dot: the limit
of low magnetic fields.
AB - Using the trion as an optical probe, we uncover novel electron spin dynamics in
CdSe/ZnSe Stranski-Krastanov quantum dots. The longitudinal spin lifetime obeys
an inverse power law associated with recharging processes in the dot ensemble. No
hint at spin-orbit mediated spin relaxation is found. At very weak magnetic
fields (< 50 mT), electron spin dynamics related to the hyperfine interaction
with the lattice nuclei is uncovered. A strong Knight field gives rise to nuclear
ordering and formation of dynamical polarization on a 100-micros time scale under
continuous electron spin pumping. The associated spin transients are temperature
robust and can be observed up to 100 K.
PMID- 17026127
TI - Effect of exchange interaction on spin dephasing in a double quantum dot.
AB - We measure singlet-triplet dephasing in a two-electron double quantum dot in the
presence of an exchange interaction which can be electrically tuned from much
smaller to much larger than the hyperfine energy. Saturation of dephasing and
damped oscillations of the spin correlator as a function of time are observed
when the two interaction strengths are comparable. Both features of the data are
compared with predictions from a quasistatic model of the hyperfine field.
PMID- 17026128
TI - Lattice relaxation in oxide heterostructures: LaTiO3/SrTiO3 superlattices.
AB - Local density approximation + Hubbard U and many-body effective Hamiltonian
calculations are used to determine the effects of lattice relaxation in
LaTiO3/SrTiO3 superlattices. Large ferroelectric-like distortions of the TiO6
octahedra are found, which substantially affect the Ti d-electron density,
bringing the calculated results into good agreement with experimental data. The
relaxations also change the many-body physics, leading to a novel symmetry
breaking-induced ordering of the xy orbitals, which does not occur in bulk
LaTiO3, or in the hypothetical unrelaxed structure.
PMID- 17026129
TI - Dephasing in (Ga,Mn)As nanowires and rings.
AB - To understand quantum mechanical transport in a ferromagnetic semiconductor, the
knowledge of basic material properties such as the phase coherence length and
corresponding dephasing mechanism are indispensable ingredients. The lack of
observable quantum phenomena has prevented experimental access to these
quantities so far. Here we report the observations of universal conductance
fluctuations in ferromagnetic (Ga,Mn)As. The analysis of the length and
temperature dependence of the fluctuations reveals a T(-1) dependence of the
dephasing time.
PMID- 17026130
TI - Abelian and non-abelian Hall liquids and charge-density wave: quantum number
fractionalization in one and two dimensions.
AB - Previously, we have demonstrated that, on a torus, the Abelian quantum Hall
liquid is adiabatically connected to a charge-density wave as the smaller
dimension of the torus is varied. In this work, we extend this result to the non
Abelian bosonic Hall state. The outcome of these works is the realization that
the paradigms of quantum number fractionalization in one dimension
(polyacetylene) and two dimensions (fractional quantum Hall effect) are, in fact,
equivalent.
PMID- 17026131
TI - Dynamics below the depinning threshold in disordered elastic systems.
AB - We study the steady-state low-temperature dynamics of an elastic line in a
disordered medium below the depinning threshold. Analogously to the equilibrium
dynamics, in the limit T-->0, the steady state is dominated by a single
configuration which is occupied with probability 1. We develop an exact algorithm
to target this dominant configuration and to analyze its geometrical properties
as a function of the driving force. The roughness exponent of the line at large
scales is identical to the one at depinning. No length scale diverges in the
steady-state regime as the depinning threshold is approached from below. We do
find a divergent length, but it is associated only with the transient relaxation
between metastable states.
PMID- 17026132
TI - Fermi surface topology and the superconducting gap function in UPd2Al3: a neutron
spin-echo study.
AB - We report on a single crystal neutron spin-echo investigation of the low-energy
dynamic response in the heavy-fermion superconductor UPd2Al3 in the vicinity of
the antiferromagnetic wave vector Q(0)=(0 0 0.5). Well inside the superconducting
phase, antiferromagnetic quasielastic scattering, which is present in the normal
state, is absent for relaxation times up to 10 ns, equivalent to an energy
resolution of approximately 1 microeV. This places strong constraints on possible
models for this magnetic superconductor.
PMID- 17026133
TI - Tunneling spectra of layered strongly correlated d-wave superconductors.
AB - Tunneling conductance experiments on cuprate superconductors exhibit a large
diversity of spectra that appear in different nanosized regions of inhomogeneous
samples. In this Letter, we use a mean-field approach to the tt't''J model in
order to address the features in these spectra that deviate from the BCS
paradigm, namely, the bias sign asymmetry at high bias, the generic lack of
evidence for the van Hove singularity, and the absence of coherence peaks at low
dopings. We conclude that these features can be reproduced in homogeneous layered
d-wave superconductors solely due to a proximate Mott insulating transition. We
also establish the connection between the above tunneling spectral features and
the strong renormalization of the electron dispersion around (0, pi) and (pi, 0)
and the momentum space anisotropy of electronic states observed in angle-resolved
photoemission spectroscopy experiments.
PMID- 17026134
TI - Reentrant superconductivity in Nb/Cu1-xNix bilayers.
AB - We report on the first observation of a pronounced reentrant superconductivity
phenomenon in a superconductor/ferromagnet layered system. The results were
obtained using a superconductor/ferromagnetic-alloy bilayer of Nb/Cu(1-x)Ni(x).
The superconducting transition temperature T(c) drops sharply with increasing
thickness dCuNi) of the ferromagnetic layer, until complete suppression of
superconductivity is observed at d(CuNi) approximately equal to 4 nm. Increasing
the Cu(1-x)Ni(x) layer thickness further, superconductivity reappears at d(CuNi)
> or =13 nm. Our experiments give evidence for the pairing function oscillations
associated with a realization of the quasi-one-dimensional Fulde-Ferrell-Larkin
Ovchinnikov-like state in the ferromagnetic layer.
PMID- 17026135
TI - Origin of nonlinear transport across the magnetically induced superconductor
metal-insulator transition in two dimensions.
AB - We have studied the effect of perpendicular magnetic fields and temperatures on
nonlinear electronic transport in amorphous Ta superconducting thin films. The
films exhibit a magnetic field-induced metallic behavior intervening the
superconductor-insulator transition in the zero temperature limit. We show that
the phase-identifying nonlinear transport in the superconducting and metallic
phases arises from an intrinsic origin, not from an electron heating effect. The
nonlinear transport is found to accompany an extraordinarily long voltage
response time.
PMID- 17026136
TI - End of aging in a complex system.
AB - Aging phenomena in complex systems have been used as an important tool to
investigate the physics of complexity. In particular, aging effects in spin
glasses, measured using the thermoremanent magnetization decays, have been
instrumental as a probe of complex equilibrium and nonequilibrium dynamics. In
this Letter, we show that aging found in spin glass materials has a finite
lifetime. After the aging part of the decay has ended, we find a post-aging decay
which is apparently logarithmic in nature. This decay is independent of the
waiting time and part of the same mechanism that produces aging.
PMID- 17026137
TI - Dynamics of field-induced ordering in magnetic colloids studied by new time
resolved small-angle neutron-scattering techniques.
AB - The reversal of magnetic moments of nanoparticles in concentrated Co ferrofluids
was monitored in an oscillating magnetic field by new time-resolved stroboscopic
small-angle neutron-scattering techniques. Time resolution in the micros range
was achieved by using a pulsed beam technique, TISANE, while in continuous mode
resolution was limited by the wavelength spread to about 1 ms. The frequency
dependence of anisotropic scattering patterns has been modeled using Langevin
dynamics. The dynamics follows a two step mechanism: field-induced ordering is
governed by fast Brownian rotation of nanoparticles with a characteristic time of
about 160 micros. Magnetic relaxation of locally ordered domains of about 100 nm
in size takes place within a few seconds by Brownian rotation or by Neel type
rotation of magnetic moments.
PMID- 17026138
TI - Nonlinear domain-wall velocity enhancement by spin-polarized electric current.
AB - The interaction between a dc spin-polarized electric current and a magnetic
domain wall in a Permalloy nanowire was studied by high-bandwidth scanning Kerr
polarimetry. The full functional dependence of wall velocity on electric current
and magnetic field is presented. With the pinning potential nulled by a field,
current-induced velocity enhancements exceeded 35 m/s at a current density of
approximately 6 x 10(11) A/m(2). This large enhancement, more than 10 times that
found in pinning-dominated experiments, results in part from an interaction that
is nonlinear in current and independent of current direction.
PMID- 17026139
TI - Ultrafast dynamics of coherences in a quantum Hall system.
AB - Using three-pulse four-wave-mixing optical spectroscopy, we study the ultrafast
dynamics of the quantum Hall system. We observe striking differences as compared
to an undoped system, where the 2D electron gas is absent. In particular, we
observe a large off-resonant signal with strong oscillations. Using a microscopic
theory, we show that these are due to many-particle coherences created by
interactions between photoexcited carriers and collective excitations of the 2D
electron gas. We extract quantitative information about the dephasing and
interference of these coherences.
PMID- 17026140
TI - Optical bistability in nonlinear surface-plasmon polaritonic crystals.
AB - Nonlinear optical transmission through periodically nanostructured metal films
(surface-plasmon polaritonic crystals) has been studied. The surface polaritonic
crystals have been coated with a nonlinear polymer. The optical transmission of
such nanostructures has been shown to depend on the control-light illumination
conditions. The resonant transmission exhibits bistable behavior with the control
light intensity. The bistability is different at different resonant signal
wavelengths and for different wavelengths of the control light. The effect is
explained by the strong sensitivity of the surface-plasmon mode resonances at the
signal wavelength to the surrounding dielectric environment and the
electromagnetic field enhancement due to plasmonic excitations at the controlled
light wavelengths.
PMID- 17026141
TI - Photoemission from buried interfaces in SrTiO3/LaTiO3 superlattices.
AB - We have measured photoemission spectra of SrTiO3/LaTiO3 superlattices with a
topmost SrTiO3 layer of variable thickness. A finite coherent spectral weight
with a clear Fermi cutoff was observed at chemically abrupt SrTiO3/LaTiO3
interfaces, indicating that an "electronic reconstruction" occurs at the
interface between the Mott insulator LaTiO3 and the band insulator SrTiO3. For
SrTiO3/LaTiO3 interfaces annealed at high temperatures (approximately 1000
degrees C), which leads to Sr/La atomic interdiffusion and hence to the formation
of La(1-x)Sr(x)TiO3-like material, the intensity of the incoherent part was found
to be dramatically reduced whereas the coherent part with a sharp Fermi cutoff
was enhanced due to the spread of charge. These important experimental features
are well reproduced by layer dynamical-mean-field-theory calculation.
PMID- 17026143
TI - Dynamics of a hard sphere granular impurity.
AB - An impurity particle coupling to its host fluid via inelastic hard sphere
collisions is considered. It is shown that the exact equation for its
distribution function can be mapped onto that for an impurity with elastic
collisions and an effective mass. The application of this result to the Enskog
Lorentz kinetic equation leads to several conclusions: (1) every solution in the
elastic case is equivalent to a class of solutions in the granular case; (2) for
an equilibrium host fluid the granular impurity approaches equilibrium at a
different temperature, with a dominant diffusive mode at long times; (3) for a
granular host fluid in its scaling state, the granular impurity approaches the
corresponding scaling solution.
PMID- 17026142
TI - Glass transition of miscible binary polymer-polymer thin films.
AB - The average glass transition temperatures, Tg, of thin homopolymer films exhibit
a thickness dependence, Tg(h), associated with a confinement effect and with
polymer-segment-interface interactions. The Tg's of completely miscible thin film
blends of tetramethyl bisphenol-A polycarbonate (TMPC) and deuterated polystyrene
(dPS), supported by SiO(x)/Si, decrease with decreasing h for PS weight fractions
phi >0.1. This dependence is similar to that of PS and opposite to that of TMPC
thin films. Based on an assessment of Tg(h, phi), we suggest that the Tg(h, phi)
of miscible blends should be rationalized, additionally, in terms of the notion
of a self-concentration and associated heterogeneous component dynamics.
PMID- 17026144
TI - Direct measurement of torque in an optical trap and its application to double
strand DNA.
AB - We present a method that offers the possibility to directly apply and measure
torque on particles in an optical trap. It can be used to rotationally manipulate
biopolymers attached to appropriate particles. A flat object is trapped and
oriented in the focus of a linearly polarized laser light. The direction and
power of the orientational trap are controlled by the polarization state of the
light. As a demonstration of the capabilities of the method, we examined the
torsional stiffness of dsDNA (lambda-DNA) in its linear torsional regime by
directly measuring the torque generated by the molecule.
PMID- 17026145
TI - Force-induced desorption and unzipping of semiflexible polymers.
AB - The thermally assisted force-induced desorption of semiflexible polymers from an
adhesive surface or the unzipping of two bound semiflexible polymers by a
localized force are investigated. The phase diagram in the force-temperature
plane is calculated both analytically and by Monte Carlo simulations. Force
induced desorption and unzipping of semiflexible polymers are first order phase
transitions. A characteristic energy barrier for desorption is predicted, which
scales with the square root of the polymer bending rigidity and governs the
initial separation process before a plateau of constant separation force is
reached. This leads to activated desorption and unzipping kinetics accessible in
single molecule experiments.
PMID- 17026146
TI - Comment on "Inseparability criteria for continuous bipartite quantum states".
PMID- 17026148
TI - Comment on "Can one predict DNA transcription start sites by studying bubbles?".
PMID- 17026150
TI - Self-localization of Bose-Einstein condensates in optical lattices via boundary
dissipation.
AB - We introduce a technique to obtain localization of Bose-Einstein condensates in
optical lattices via boundary dissipations. Stationary and traveling localized
states are generated by removing atoms at the optical lattice ends. Clear regimes
of stretched-exponential decay for the number of atoms trapped in the lattice are
identified. The phenomenon is universal and can also be observed in arrays of
optical waveguides with mirrors at the system boundaries.
PMID- 17026151
TI - Long-lived BLOCH oscillations with bosonic sr atoms and application to gravity
measurement at the micrometer scale.
AB - We report on the observation of Bloch oscillations on the unprecedented time
scale of several seconds. The experiment is carried out with ultracold bosonic
88Sr atoms loaded into a vertical optical standing wave. The negligible atom-atom
elastic cross section and zero angular momentum in the ground state makes 88Sr an
almost ideal Bose gas, insensitive to typical mechanisms of decoherence due to
thermalization and external stray fields. The small size of the system enables
precision measurements of forces at micrometer scale. This is a challenge in
physics for studies of surfaces, Casimir effects, and searches for deviations
from Newtonian gravity predicted by theories beyond the standard model.
PMID- 17026152
TI - Formation of spatial shell structure in the superfluid to Mott insulator
transition.
AB - We report on the direct observation of the transition from a compressible
superfluid to an incompressible Mott insulator by recording the in-trap density
distribution of a Bosonic quantum gas in an optical lattice. Using spatially
selective microwave transitions and spin-changing collisions, we are able to
locally modify the spin state of the trapped quantum gas and record the spatial
distribution of lattice sites with different filling factors. As the system
evolves from a superfluid to a Mott insulator, we observe the formation of a
distinct shell structure, in good agreement with theory.
PMID- 17026153
TI - Master equation for a quantum particle in a gas.
AB - The equation for the quantum motion of a Brownian particle in a gaseous
environment is derived by means of S-matrix theory. This quantum version of the
linear Boltzmann equation accounts nonperturbatively for the quantum effects of
the scattering dynamics and describes decoherence and dissipation in a unified
framework. As a completely positive master equation it incorporates both the
known equation for an infinitely massive Brownian particle and the classical
linear Boltzmann equation as limiting cases.
PMID- 17026154
TI - Infrared imaging of single nanoparticles via strong field enhancement in a
scanning nanogap.
AB - We demonstrate nanoscale resolved infrared imaging of single nanoparticles
employing near-field coupling in the nanoscopic gap between the metal tip of a
scattering-type near-field optical microscope and the substrate supporting the
particles. Experimental and theoretical evidence is provided that highly
reflecting or polariton-resonant substrates strongly enhance the near-field
optical particle contrast. Using Si substrates we succeeded in detecting Au
particles as small as 8 nm (KK decays through flavor symmetries and QCD factorization.
AB - We present a new analysis of Bd,s-->KK modes within the standard model (SM),
relating them in a controlled way through SU(3)-flavor symmetry and QCD-improved
factorization. We propose a set of sum rules for Bd,s-->K0K0 observables. We
determine Bs-->KK branching ratios and CP asymmetries as functions of Adir(Bd-
>K0K0), pointing out a conflict between BR(Bs-->K+K-) in the SM and data.
Finally, we predict the amount of U-spin breaking between Bd-->pi+pi- and Bs-
>K+K-.
PMID- 17026159
TI - Top quark mediated Higgs boson decay into hadrons to order alphas5.
AB - We present in analytic form the O(alphas5) correction to the H-->gg partial width
of the standard-model Higgs boson with an intermediate mass MH<2Mt. Its knowledge
is useful because the O(alphas4) correction is sizable (around 20%). For MH=120
GeV, the resulting QCD correction factor reads
1+(215/12)alphas(5)(MH)/pi+152.5[alphas(5)(MH)/pi]2+381.5[alphas(5)(MH)/pi]3
approximately 1+0.65+0.20+0.02. The new four-loop correction increases the total
Higgs-boson hadronic width by a small amount of order 1 per thousand and
stabilizes significantly the residual scale dependence.
PMID- 17026162
TI - piN-->etaN data require the existence of the N(1710) P11 resonance, reducing the
1700-MeV continuum ambiguity.
AB - In spite of long-lasting discussions, the agreement on the existence of the
N(1710) P11 resonance has not yet been reached, so the Particle Data Group
declares it as a 3-star resonance only. We show that the proper inclusion of
inelastic channels in the coupled-channel formalism indisputably demands the
existence of the N(1710) P11 state, and that it presumably stays hidden within
the continuum ambiguity of a typical single-channel partial-wave analysis.
Consequently, the Particle Data Group confidence rating of this state should be
raised to a 4-star resonance.
PMID- 17026158
TI - Evidence for B-->eta'pi and improved measurements for B-->eta'K.
AB - We report evidence for the exclusive two-body charmless hadronic B meson decay B-
>eta'pi, and improved measurements of B-->eta'K. The results are obtained from a
data sample of 386x10(6) BB pairs collected at the Upsilon(4S) resonance, with
the Belle detector at the KEKB asymmetric-energy e+e- collider. We measure B(B+-
>eta'pi+)=[1.76(-0.62)(+0.67)(stat)(-0.14)(+0.15)(syst)]x10(-6) and B(B0-
>eta'pi0)=[2.79(-0.96)(+1.02)(stat)(-0.34)(+0.25)(syst)]x10(-6). We also find the
ratio of B(B+-->eta'K+)/B(B0-->eta'K0)=1.17+/-0.08(stat)+/-0.03(syst) and measure
the direct CP asymmetries for the charged modes.
PMID- 17026160
TI - Measurement of D0-->pilnu(Klnu) form factors and absolute branching fractions.
AB - Using a 282 fb-1 data sample collected by the Belle experiment at the KEKB e+e-
collider, we study D0 decays to K-l+nu and pi-l+nu final states. The D0 flavor
and momentum are tagged through a full reconstruction of the recoiling charm
meson and additional mesons from fragmentation. The reconstruction method
provides very good resolution in neutrino momentum and in q2=(pl+pnu)2.
Normalizing to the total number of D0 tags, we measure the absolute branching
fractions to be B(D0-->Klnu)=(3.45+/-0.07stat+/-0.20syst)% and B(D0-
>pilnu)=(0.255+/-0.019stat+/-0.016syst)% and the semileptonic form factors
(within the modified pole model) f+K(0)=0.695+/-0.007stat+/-0.022syst and
f+pi(0)=0.624+/-0.020stat+/-0.030syst.
PMID- 17026161
TI - Observation of two new N* peaks in J/psi-->ppi-n and ppi+n decays.
AB - The decay J/psi-->NNpi provides an effective isospin 1/2 filter for the piN
system due to isospin conservation. Using 58x10(6) J/psi decays collected with
the Beijing Electromagnetic Spectrometer at the Beijing Electron Positron
Collider, more than 100 thousand J/psi-->ppi-n+c.c. events are obtained. Besides
the two well-known N* peaks at around 1500 MeV/c2 and 1670 MeV/c2, there are two
new, clear N* peaks in the ppi invariant mass spectrum around 1360 MeV/c2 and
2030 MeV/c2 with statistical significance of 11sigma and 13sigma, respectively.
We identify these as the first direct observation of the N*(1440) peak and a long
sought missing N* peak above 2 GeV/c2 in the piN invariant mass spectrum.
PMID- 17026164
TI - Effects of jet quenching on the hydrodynamical evolution of quark-gluon plasma.
AB - We study the effects of jet quenching on the hydrodynamical evolution of the
quark-gluon plasma (QGP) fluid created in a heavy-ion collision. In jet
quenching, a hard QCD parton, before fragmenting into a jet of hadrons, deposits
a fraction of its energy in the medium, leading to suppressed production of high
pT hadrons. Assuming that the deposited energy quickly thermalizes, we simulate
the subsequent hydrodynamic evolution of the QGP fluid. For partons moving at
supersonic speed, vp>cs, and sufficiently large energy loss, a shock wave forms
leading to conical flow. The PHENIX Collaboration recently suggested that
observed structures in the azimuthal angle distribution might be caused by
conical flow. We show here that, for phenomenologically acceptable values of
parton energy loss, conical flow effects are too weak to explain these
structures.
PMID- 17026165
TI - Collectivity and configuration mixing in 186,188Pb and 194Po.
AB - Lifetimes of prolate intruder states in 186Pb and oblate intruder states in 194Po
have been determined by employing, for the first time, the recoil-decay tagging
technique in recoil distance Doppler-shift lifetime measurements. In addition,
lifetime measurements of prolate states in 188Pb up to the 8+ state were carried
out using the recoil-gating method. The B(E2) values have been deduced from which
deformation parameters |beta2|=0.29(5) and |beta2|=0.17(3) for the prolate and
the oblate bands, respectively, have been extracted. The results also shed new
light on the mixing between different shapes.
PMID- 17026166
TI - Gamow-Teller strengths in the A = 14 multiplet: a challenge to the shell model.
AB - A new experimental approach to the famous problem of the anomalously slow Gamow
Teller (GT) transitions in the beta decay of the A=14 multiplet is presented. The
GT strength distributions to excited states in 14C and 14O were studied in high
resolution (d,2He) and (3He,t) charge-exchange reactions on 14N. No-core shell
model calculations capable of reproducing the suppression of the beta decays
predict a selective excitation of Jpi=2+ states. The experimental confirmation
represents a validation of the assumptions about the underlying structure of the
14N ground state wave function. However, the fragmentation of the GT strength
over three 2+ final states remains a fundamental issue not explained by the
present no-core shell model using a 6homega model space, suggesting possibly the
need to include cluster structure in these light nuclei in a consistent way.
PMID- 17026167
TI - Efimov states and their Fano resonances in a neutron-rich nucleus.
AB - Asymmetric resonances in elastic n+19C scattering are attributed to Efimov states
of such neutron-rich nuclei, that is, three-body bound states of the n+n+18C
system when none of the pairs is bound or some of them are only weakly bound. By
fitting to the general resonance shape described by Fano, we extract the
resonance position, width, and the "Fano profile index." While Efimov states have
been discussed extensively in many areas of physics, there is only one very
recent experimental observation in trimers of cesium atoms. The conjunction that
we present of the Efimov and Fano phenomena may lead to experimental realization
in nuclei.
PMID- 17026168
TI - Identification of mixed-symmetry states in an odd-mass nearly spherical nucleus.
AB - The low-spin structure of 93Nb has been studied using the (n,n'gamma) reaction at
neutron energies ranging from 1.5 to 3 MeV and the 94Zr(p,2ngamma)93Nb reaction
at bombarding energies from 11.5 to 19 MeV. States at 1779.7 and 1840.6 keV,
respectively, are proposed as mixed-symmetry states associated with the pi2p(1/2)
1x(2(1),MS+,94Mo) coupling. These assignments are derived from the observed M1
and E2 transition strengths to the 2p(1/2)-1x(2(1)+,94Mo) symmetric one-phonon
states, energy systematics, spins and parities, and comparison with shell model
calculations.
PMID- 17026169
TI - Proposal for a sensitive search for the electric dipole moment of the electron
with matrix-isolated radicals.
AB - We propose using matrix-isolated paramagnetic diatomic molecules to search for
the electric dipole moment of the electron (eEDM). As was suggested by Shapiro in
1968, the eEDM leads to a magnetization of a sample in the external electric
field. In a typical condensed matter experiment, the effective field on the
unpaired electron is of the same order of magnitude as the laboratory field,
typically about 10(5) V/cm. We exploit the fact that the effective electric field
inside heavy polar molecules is on the order of 10(10) V/cm. This leads to a huge
enhancement of the Shapiro effect. Statistical sensitivity of the proposed
experiment may allow one to improve the current limit on eEDM by 3 orders of
magnitude in a few hours accumulation time.
PMID- 17026170
TI - Large cross-phase modulation between slow copropagating weak pulses in 87Rb.
AB - We propose a scheme to generate double electromagnetically induced transparency
and optimal cross-phase modulation for two slow, copropagating pulses with
matched group velocities in a single species of atom, namely 87Rb. A single pump
laser is employed and a homogeneous magnetic field is utilized to avoid
cancellation effects through the nonlinear Zeeman effect. We suggest a feasible
preparational procedure for the atomic initial state to achieve matched group
velocities for both signal fields.
PMID- 17026171
TI - Coalescence of spreading droplets on a wettable substrate.
AB - We investigate experimentally and theoretically the coalescence dynamics of two
spreading droplets on a highly wettable substrate. Upon contact, surface tension
drives a rapid motion perpendicular to the line of centers that joins the drops
and lowers the total surface area. We find that the width of the growing meniscus
bridge between the two droplets exhibits power-law behavior, growing at early
times as t1/2. Moreover, the growth rate is highly sensitive to both the radii
and heights of the droplets at contact, scaling as ho3/2/Ro. This size dependence
differs significantly from the behavior of freely suspended droplets, in which
the coalescence growth rate depends only weakly on the droplet size. We
demonstrate that the scaling behavior is consistent with a model in which the
growth of the meniscus bridge is governed by the viscously hindered flux from the
droplets.
PMID- 17026172
TI - Order-chaos-order transitions in electrosprays: the electrified dripping faucet.
AB - Electrosprays have diverse applications including protein analysis,
electrospinning, and nanoencapsulation for drug delivery. We show that a variety
of electrospray regimes exhibit fundamental analogy with the nonlinear dynamics
of a dripping faucet. The applied voltage in electrosprays results in additional
period doublings and temporal order-chaos-order transitions. Attractors in the
return maps show logarithmic self-similarity in time, suggesting self-similar
capillary waves on the meniscus. The bifurcations in ejection time can be
explained by phase variations between capillary waves and pinch-off conditions
and by ejection mode changes due to contact angle variations.
PMID- 17026173
TI - Geometric simulation of perovskite frameworks with Jahn-Teller distortions:
applications to the cubic manganites.
AB - A new approach is presented for modeling perovskite frameworks with disordered
Jahn-Teller (JT) distortions and has been applied to study the elastic response
of the LaMnO3 structure to defects in the JT ordering. Surprisingly, antiphase
domain boundary defects in the pattern of ordered JT octahedra, along the [110]
and [110] bonding directions, are found to produce 1D stripe patterns rotated 45
degrees along a* directions, similar to stripe structures observed in these
systems. Geometric simulation is shown to be an efficient and powerful approach
for finding relaxed atomic structures in the presence of disorder in networks of
corner-shared JT-distorted octahedra such as the perovskites. Geometric modeling
rapidly relaxes large supercells (thousands of octahedra) while preserving the
local coordination chemistry, and shows great promise for studying these complex
systems.
PMID- 17026174
TI - Cooperative shear model for the rheology of glass-forming metallic liquids.
AB - A rheological law based on the concept of cooperatively sheared flow zones is
presented, in which the effective thermodynamic state variable controlling flow
is identified to be the isoconfigurational shear modulus of the liquid. The law
captures Newtonian as well as non-Newtonian viscosity data for glass-forming
metallic liquids over a broad range of fragility. Acoustic measurements on
specimens deformed at a constant strain rate correlate well with the measured
steady-state viscosities, hence verifying that viscosity has a unique functional
relationship with the isoconfigurational shear modulus.
PMID- 17026175
TI - Heterogeneous nucleation in and out of pores.
AB - We study the nucleation of a new thermodynamic phase in pores and find that the
nucleation often proceeds via two steps: nucleation of pore filling, and
nucleation out of the pore. These two rates have opposing dependencies on pore
size, resulting in a pore size at which the nucleation rate of the new phase is
maximal. This finding is relevant to attempts to design and use porous media to
crystallize proteins.
PMID- 17026176
TI - Two-dimensional Ising model criticality in a three-dimensional uniaxial relaxor
ferroelectric with frozen polar nanoregions.
AB - The charge-disordered three-dimensional uniaxial relaxor ferroelectric
Sr0.61Ba0.39Nb2O6 splits up into metastable polar nanoregions and paraelectric
interfaces upon cooling from above Tc. The frozen polar nanoregions are verified
by piezoresponse force microscopy, respond domainlike to dynamic light scattering
and dielectric excitation, reveal nonergodicity at T>Tc via global aging, and
coalesce into polar nanodomains below Tc. Contrastingly, the percolating system
of unperturbed interfaces becomes ferroelectric with two-dimensional Ising-model
like critical exponents alpha=0, beta=1/8, and gamma=7/4, as corroborated by ac
calorimetry, second harmonic generation, and susceptometry, respectively.
PMID- 17026163
TI - Measurement of the Bs0-Bs0 oscillation frequency.
AB - We present the first precise measurement of the Bs0-Bs0 oscillation frequency
Deltams. We use 1 fb-1 of data from pp collisions at sqrts=1.96 TeV collected
with the CDF II detector at the Fermilab Tevatron. The sample contains signals of
3600 fully reconstructed hadronic Bs decays and 37,000 partially reconstructed
semileptonic Bs decays. We measure the probability as a function of proper decay
time that the Bs decays with the same, or opposite, flavor as the flavor at
production, and we find a signal consistent with Bs0-Bs0 oscillations. The
probability that random fluctuations could produce a comparable signal is 0.2%.
Under the hypothesis that the signal is due to Bs0-Bs0 oscillations, we measure
Deltams=17.31(-0.18)+0.33(stat)+/-0.07(syst) ps-1 and determine |Vtd/Vts|=0.208(
0.002)+0.001(expt)-0.006(+0.008)(theor).
PMID- 17026177
TI - Collapse of transient nucleation fluxes in a cold Ising ferromagnet.
AB - We report the time-dependent nucleation fluxes and associated nucleation rates in
a metastable Ising ferromagnet on square lattice with Metropolis (Glauber-type)
dynamics. It is discovered that, with lowering of the temperature, fluxes
collapse into several representative transient curves corresponding to magic
cluster sizes. Those can be associated with physical droplets, i.e., long-lived
configurations which provide a link with the classical Becker-Doring picture.
PMID- 17026178
TI - From ultraslow to fast lithium diffusion in the 2D ion conductor Li0.7TiS2 probed
directly by stimulated-echo NMR and nuclear magnetic relaxation.
AB - 7Li stimulated-echo NMR and classical relaxation NMR techniques are jointly used
for the first time for a comprehensive investigation of Li diffusion in layer
structured Li0.7TiS2. One single 2D Li diffusion process was probed over a
dynamic range of almost 10 orders of magnitude. So far, this is the largest
dynamic range being measured by 7Li NMR spectroscopy directly, i.e., without the
help of a specific theoretical model. The jump rates obey a strict Arrhenius law,
determined by an activation energy of 0.41(1) eV and a preexponential factor of
6.3(1)x10(12) s-1, and range between 1x10(-1) s-1 and 7.8x10(8) s-1 (148-510 K).
Ultraslow Li jumps in the kHz to sub-Hz range were measured directly by recording
7Li spin-alignment correlation functions. The temperature and, in particular, the
frequency dependence of the relaxation rates fully agree with results expected
for 2D diffusion.
PMID- 17026179
TI - Structure and interconversion of oxygen-vacancy-related defects on amorphous
silica.
AB - Atomic structure and structural stability of neutral oxygen vacancies on
amorphous silica are investigated using combined Monte Carlo and density
functional calculations. We find that, unlike their bulk counterparts, the Si-Si
dimer configuration of surface oxygen vacancies is likely to be unstable due to
the high tensile strains induced, thereby undergoing thermally activated
transformation with a moderate barrier into other stable configurations including
dicoordinated silicon, silanone, or a subsurface Si-Si dimer, depending on the
local surface structure. Pathways for the interconversion between these oxygen
vacancy-related defects are presented with a discussion of their viability.
PMID- 17026180
TI - Crossover from stretched to compressed exponential relaxations in a polymer-based
sponge phase.
AB - X-ray photon correlation spectroscopy was used to characterize the wave vector-
and temperature-dependent dynamics of spontaneous thermal fluctuations in a
sponge (L3) phase that occurs in a blend of a symmetric poly(styrene
ethylene/butylene-styrene) triblock copolymer with a polystyrene homopolymer.
Measurements of the intermediate scattering function reveal a crossover from
stretched- to compressed-exponential relaxations as the temperature is lowered
from 180 to 120 degrees C.
PMID- 17026181
TI - Symmetric liquid-liquid interface with a nonzero spontaneous curvature.
AB - The curvature dependence of the symmetric interface between two immiscible
polymer solutions in a common monomeric solvent is analyzed using a self
consistent field theory. Contrary to symmetry arguments we find that the surface
tension depends in first order on a nonzero Tolman length. These interfaces
further have a negative mean and a positive Gaussian bending modulus. The finite
spontaneous curvature is attributed to the adsorption of the solvent at the
interface.
PMID- 17026182
TI - Mott transition in kagome lattice Hubbard model.
AB - We investigate the Mott transition in the kagome lattice Hubbard model using a
cluster extension of dynamical mean field theory. The calculation of the double
occupancy, the density of states, and the static and dynamical spin correlation
functions demonstrates that the system undergoes the first-order Mott transition
at the Hubbard interaction U/W approximately 1.4 (W:bandwidth). In the metallic
phase close to the Mott transition, we find the strong renormalization of three
distinct bands, giving rise to the formation of heavy quasiparticles with strong
frustrated interactions. It is elucidated that the quasiparticle states exhibit
anomalous behavior in the temperature-dependent spin correlation functions.
PMID- 17026183
TI - Polarization and propagation of polariton condensates.
AB - With the use of the generalized Gross-Pitaevskii equation it is shown that
exciton polaritons in semiconductor microcavities form a linearly polarized
condensate having two branches of the excitation spectrum. The splitting between
these branches is strongly anisotropic. This anisotropy noticeably affects the
real-space dynamics of polariton condensates.
PMID- 17026184
TI - Spin-Hall conductivity in electron-phonon coupled systems.
AB - We derive the ac spin-Hall conductivity sigmasH(omega) of two-dimensional spin
orbit coupled systems interacting with dispersionless phonons of frequency
omega0. For the linear Rashba model, we show that the electron-phonon
contribution to the spin-vertex corrections breaks the universality of
sigmasH(omega) at low frequencies and provides a nontrivial renormalization of
the interband resonance. On the contrary, in a generalized Rashba model for which
the spin-vertex contributions are absent, the coupling to the phonons enters only
through the self-energy, leaving the low-frequency behavior of sigmasH(omega)
unaffected by the electron-phonon interaction.
PMID- 17026185
TI - Electrically detected electron spin resonance in a high-mobility silicon quantum
well.
AB - The resistivity change due to electron spin resonance (ESR) absorption is
investigated in a high-mobility two-dimensional electron system formed in a
Si/SiGe heterostructure. Results for a specific Landau level configuration
demonstrate that the primary cause of the ESR signal is a reduction of the spin
polarization, not the effect of electron heating. The longitudinal spin
relaxation time T1 is obtained to be of the order of 1 ms in an in-plane magnetic
field of 3.55 T. The suppression of the effect of the Rashba fields due to high
frequency spin precession explains the very long T1.
PMID- 17026187
TI - Positive current correlations associated with super-Poissonian shot noise.
AB - We report on shot noise cross spectrum measurements in a beam splitter
configuration. Electrons tunneling through potential barriers are incident on a
beam splitter and scattered into two separate channels. Such a partition process
introduces correlations between the fluctuations of the two currents. Our work
has confirmed that the generally expected negative correlations resulted from sub
Poissonian electron sources. More interestingly, positive cross correlations
associated with barriers exhibiting super-Poissonian shot noise have also been
observed. We have found that both positive and negative correlations can be
related to the noise properties of the electron source.
PMID- 17026186
TI - Universal spin-Hall conductance fluctuations in two dimensions.
AB - We report a theoretical investigation on spin-Hall conductance fluctuation of
disordered four-terminal devices in the presence of Rashba or/and Dresselhaus
spin-orbital interactions in two dimensions. As a function of disorder, the spin
Hall conductance GsH shows ballistic, diffusive, and insulating transport
regimes. For given spin-orbit interactions, a universal spin-Hall conductance
fluctuation (USCF) is found in the diffusive regime. The value of the USCF
depends on the spin-orbit coupling tso but is independent of other system
parameters. It is also independent of whether Rashba or Dresselhaus or both spin
orbital interactions are present. When tso is comparable to the hopping energy t,
the USCF is a universal number approximately 0.18e/4pi. The distribution of GsH
crosses over from a Gaussian distribution in the metallic regime to a non
Gaussian distribution in the insulating regime as the disorder strength is
increased.
PMID- 17026188
TI - Full-counting statistics for voltage and dephasing probes.
AB - We present a stochastic path integral method to calculate the full-counting
statistics of conductors with energy conserving dephasing probes and dissipative
voltage probes. The approach is explained for the experimentally important case
of a Mach-Zehnder interferometer, but is easily generalized to more complicated
setups. For all geometries where dephasing may be modeled by a single one-channel
dephasing probe we prove that our method yields the same full-counting statistics
as phase averaging of the cumulant generating function.
PMID- 17026189
TI - Fluctuation-exchange study of antiferromagnetism in disordered electron-doped
cuprate superconductors.
AB - On the basis of the Hubbard model, we extend the fluctuation-exchange (FLEX)
approach to investigating the properties of the antiferromagnetic (AF) phase in
electron-doped cuprate superconductors. Furthermore, by incorporating the effect
of scatterings due to the disordered dopant atoms into the FLEX formalism, our
numerical results show that the antiferromagnetic transition temperature, the
onset temperature of pseudogap due to spin fluctuations, the spectral density of
the single particle near the Fermi surface, and the staggered magnetization in
the AF phase as a function of electron doping can consistently account for the
experimental measurements.
PMID- 17026190
TI - Orbital ordering and Jahn-Teller distortion in Perovskite ruthenate SrRuO3.
AB - Local density approximation plus on-site Coulomb interaction U band structure
calculations reveal that SrRuO3 exhibits a half-metallic ground state with an
integer spin moment of 2.0 microB/SrRuO3. An associated tilting 4dt2g orbital
ordering on a Ru sublattice is observed under the on-site Coulomb interaction U
in the presence of lattice distortion. This finding unravels the on-site Coulomb
correlation as the driving force of the 4d orbital ordering and Jahn-Teller
distortion as well as of the half-metallic ground state.
PMID- 17026191
TI - Flux-flow resistivity anisotropy in the instability regime of the a-b plane of
epitaxial superconducting YBa2Cu3O7-delta thin films.
AB - Measurements of the nonlinear flux-flow resistivity rho and the critical vortex
velocity vphi* at high voltage bias close to the instability regime predicted by
Larkin and Ovchinnikov (Z. Eksp. Teor. Fiz 68, 1915 (1975) [Sov. Phys. JETP 41,
960 (1976)]) are reported along the node and antinode directions of the d-wave
order parameter in the a-b plane of epitaxial YBa2Cu3O7-delta films. In this
pinning-free regime, rho and vphi* are found to be anisotropic with values in the
node direction larger on average by 10% than in the antinode direction. The
anisotropy of rho is almost independent of temperature and field. We attribute
the observed results to the anisotropic quasiparticle distribution on the Fermi
surface of YBa2Cu3O7-delta.
PMID- 17026192
TI - Spectrum of the Andreev billiard and giant fluctuations of the Ehrenfest time.
AB - The density of states in the semiclassical Andreev billiard is theoretically
studied and shown to be determined by the fluctuations of the classical Lyapunov
exponent lambda. The rare trajectories with a small value of lambda give rise to
an anomalous increase of the Ehrenfest time tauE approximately |lnvariant
Planck's over 2pi|/lambda and, consequently, to the appearance of Andreev levels
with small excitation energy. The gap in spectrum is obtained, and fluctuations
of the value of the gap due to different positions of superconducting lead are
considered.
PMID- 17026193
TI - Thermal conductivity in the vicinity of the quantum critical end point in
Sr3Ru2O7.
AB - Thermal conductivity of Sr3Ru2O7 was measured down to 40 mK and at magnetic
fields through the quantum critical end point at Hc=7.85 T. A peak in the
electrical resistivity as a function of the field was mimicked by the thermal
resistivity. In the limit as T-->0 K, we find that the Wiedemann-Franz law is
satisfied to within 5% at all fields, implying that there is no breakdown of the
electron despite the destruction of the Fermi liquid state at quantum
criticality. A significant change in disorder [from rho0(H=0 T)=2.1 to 0.5
microOmega cm] does not influence our conclusions. At finite temperatures, the
temperature dependence of the Lorenz number is consistent with ferromagnetic
fluctuations causing the non-Fermi liquid behavior as one would expect at a
metamagnetic quantum critical end point.
PMID- 17026194
TI - Superconducting atomic contacts under microwave irradiation.
AB - We have measured the effect of microwave irradiation on the dc current-voltage
characteristics of superconducting atomic contacts. The interaction of the
external field with the ac supercurrents leads to replicas of the supercurrent
peak, the well-known Shapiro resonances. The observation of supplementary
fractional resonances for contacts containing highly transmitting conduction
channels reveals their nonsinusoidal current-phase relation. The resonances sit
on a background current which is itself deeply modified, as a result of photon
assisted multiple Andreev reflections. The results provide firm support for the
full quantum theory of transport between two superconductors based on the concept
of Andreev bound states.
PMID- 17026195
TI - Specular Andreev reflection in graphene.
AB - By combining the Dirac equation of relativistic quantum mechanics with the
Bogoliubov-de Gennes equation of superconductivity we investigate the electron
hole conversion at a normal-metal-superconductor interface in graphene. We find
that the Andreev reflection of Dirac fermions has several unusual features: (1)
the electron and hole occupy different valleys of the band structure; (2) at
normal incidence the electron-hole conversion happens with unit efficiency in
spite of the large mismatch in Fermi wavelengths at the two sides of the
interface; and, most fundamentally: (3) away from normal incidence the reflection
angle may be the same as the angle of incidence (retroreflection) or it may be
inverted (specular reflection). Specular Andreev reflection dominates in weakly
doped graphene, when the Fermi wavelength in the normal region is large compared
to the superconducting coherence length.
PMID- 17026196
TI - Imprinting vortices into antiferromagnets.
AB - The effect of imprinting symmetric and displaced vortex structures into an
antiferromagnetic material is investigated in micron-sized disks consisting of
exchange coupled ferromagnetic-antiferromagnetic bilayers. The imprint of
displaced vortices manifests itself by the occurrence of a new type of asymmetric
hysteresis loops characterized by curved, reversible, central sections with
nonzero remanent magnetization. Such an imprint is achieved by cooling the disks
through the blocking temperature of the system in small fields. Micromagnetic
simulations reveal that asymmetric vortexlike loops naturally result from the
competition between the different energies involved in the system.
PMID- 17026197
TI - Spin nematics and magnetization plateau transition in anisotropic kagome magnets.
AB - We study S=1 kagome antiferromagnets with an isotropic Heisenberg exchange J and
strong easy-axis single-ion anisotropy D. For D>>J, the low-energy physics can be
described by an effective S=1/2 XXZ model with antiferromagnetic Jz approximately
J and ferromagnetic J perpendicular approximately J2/D. Exploiting this
connection, we argue that nontrivial ordering into a "spin-nematic" occurs
whenever D dominates over J, and discuss its experimental signatures. We also
study a magnetic field induced transition to a magnetization plateau state at
magnetization 1/3 which breaks lattice translation symmetry due to ordering of
the Sz and occupies a lobe in the B/Jz-Jz/J perpendicular phase diagram.
PMID- 17026198
TI - Magnetocrystalline anisotropy in permalloy revisited.
AB - Permalloy with a body-centered-cubic structure has been grown on GaAs(001) by
molecular beam epitaxy. Its magnetism, Curie temperature, and magnetic anisotropy
are determined experimentally and compared to those of conventional face-centered
cubic Permalloy. Unexpectedly the vanishing magnetic cubic anisotropy in
Permalloy is found to be independent of its atomic structure but depends only
upon the stoichiometry of Fe and Ni in the FexNi1-x alloy. This observation is
further investigated and confirmed by first-principles electronic band
calculations, which help to understand the long-standing issue of why Permalloy
should be a soft magnet.
PMID- 17026199
TI - Elastic domains in antiferromagnets on substrates.
AB - We consider periodic domain structures which appear due to the magnetoelastic
interaction if the antiferromagnetic crystal is attached to an elastic substrate.
The peculiar behavior of such structures in an external magnetic field is
discussed. In particular, we find the magnetic field dependence of the
equilibrium period and the concentrations of different domains.
PMID- 17026200
TI - Giant spin-orbit bowing in GaAs1-xBix.
AB - We report a giant bowing of the spin-orbit splitting energy Delta0 in the dilute
GaAs1-xBix alloy for Bi concentrations ranging from 0% to 1.8%. This is the first
observation of a large relativistic correction to the host electronic band
structure induced by just a few percent of isoelectronic doping in a
semiconductor material. It opens up the possibility of tailoring the spin-orbit
splitting in semiconductors for spintronic applications.
PMID- 17026201
TI - Spin-lattice interaction in the quasi-one-dimensional helimagnet LiCu2O2.
AB - The field dependence of the electron spin resonance in a helimagnet LiCu2O2 was
investigated for the first time. In the paramagnetic state, a broad resonance
line was observed corresponding to a g factor of 2.3. In the critical regime,
around the paramagnetic to helimagnetic phase transition the resonance broadens
and shifts to higher frequencies. A narrow signal is recovered at a low
temperature, corresponding to a spin gap of 1.4 meV in zero field. A
comprehensive model of the magnons is presented, using exchange parameters from
neutron scattering [T. Masuda Phys. Rev. B 72, 014405
(2005)10.1103/PhysRevB.72.014405] and the spin anisotropy determined here. The
role of the quantum fluctuations is discussed.
PMID- 17026202
TI - Mechanism of carrier photogeneration and carrier transport in molecular crystal
tetracene.
AB - Models for the carrier photoexcitation mechanism in molecular crystals have been
established initially on the bases of measurements on oligoacenes and later
applied to conjugated polymers as well. These models emphasize the localized
nature of photoexcitations and describe carrier generation as a secondary process
involving exciton dissociation. The results of our photoconductivity studies of
single crystal tetracene are at variance with these widely accepted models, and
in fact indicate that the photocarrier quantum efficiency appears independent of
temperature, photon energy, and light intensity, thus featuring the hallmarks of
direct interband carrier photogeneration and coherent carrier transport at band
states.
PMID- 17026203
TI - Time evolution of the electronic structure of 1T-TaS2 through the insulator-metal
transition.
AB - Femtosecond time-resolved photoemission is used to investigate the time evolution
of electronic structure in the Mott insulator 1T-TaS2. A collapse of the
electronic gap is observed within 100 femtoseconds after optical excitation. The
photoemission spectra and the spectral function calculated by dynamical mean
field theory show that this insulator-metal transition is driven solely by hot
electrons. A coherently excited lattice displacement results in a periodic shift
of the spectra lasting for 20 ps without perturbing the insulating phase. This
capability to disentangle electronic and phononic excitations opens new
directions to study electron correlation in solids.
PMID- 17026204
TI - Trapped electromagnetic modes and scaling in the transmittance of perforated
metal films.
AB - We describe measurements and simulations of the enhanced transmittance by
subwavelength hole arrays in silver films. The array period and hole size are
systematically varied to give peak transmittances at wavelengths spanning a
factor of 14. The spectra coincide when scaled using the array geometry and
substrate refractive index alone, thus showing no significant dependence on the
dielectric function of the metal. We argue that the spectra can be explained by
interference of diffractive and resonant scattering. The resonant contribution
comes from electromagnetic modes trapped in the film vicinity.
PMID- 17026205
TI - Polymer-population mapping and localization in the space of phenotypes.
AB - We present a mapping between the thermodynamics of an ideal heteropolymer in an
external field and the dynamics of structured populations in fluctuating
environments. We employ a population model in which individuals may adopt
different phenotypes, each of which may be optimal in a different environment.
Using this mapping, we develop a path integral formulation for populations and
predict the existence of a biological counterpart for the well-known
heteropolymer localization phase transition.
PMID- 17026206
TI - Signal detection, modularity, and the correlation between extrinsic and intrinsic
noise in biochemical networks.
AB - We present an expression for the power spectrum of the output signal of a
biochemical network, which reveals that the reactions that allow a network to
detect biochemical signals, induce correlations between the extrinsic noise of
the input signals and the intrinsic noise of the reactions that form the network.
We show that anticorrelations between the extrinsic and intrinsic noise enhance
the robustness of zero-order ultrasensitive networks to biochemical noise. We
discuss the consequences for a modular description of noise transmission using
the mitogen-activated protein kinase cascade.
PMID- 17026207
TI - Solubility and charge inversion of complexes of DNA and basic proteins.
AB - The basic proteins, protamines and histones H1, are known to condense DNA in
vivo. We examine here their ability to condense and solubilize in vitro linear
DNA [and a synthetic polyanion, Poly(Styrene-Sulfonate) or PSS] at low ionic
concentrations by varying the charge concentration ratio. Phase separation is
observed in a very narrow range of ratios for short DNA and PSS; on both sides of
this range, polydisperse and charged complexes are formed. A charge inversion is
detected. For long DNA chains however, a different behavior is observed: the
complexes are not soluble in excess of proteins.
PMID- 17026208
TI - Filamin cross-linked semiflexible networks: fragility under strain.
AB - The semiflexible F-actin network of the cytoskeleton is cross-linked by a variety
of proteins including filamin, which contains Ig domains that unfold under
applied tension. We examine a simple filament network model cross-linked by such
unfolding linkers that captures the main mechanical features of F-actin networks
cross-linked by filamin proteins and show that, under sufficient strain, the
network spontaneously self-organizes so that an appreciable fraction of the
filamin cross-linkers are at the threshold of domain unfolding. We propose and
test a mean-field model to account for this effect. We also suggest a qualitative
experimental signature of this type of network reorganization under applied
strain that may be observable in intracellular microrheology experiments of
Crocker et al.
PMID- 17026209
TI - Snake's perspective on heat: reconstruction of input using an imperfect detection
system.
AB - Two groups of snakes possess an infrared detection system that is used to create
a heat image of their environment. In this Letter we present an explicit
reconstruction model, the "virtual lens," which explains how a snake can overcome
the optical limitations of a wide aperture pinhole camera, and how ensuing
properties of the receptive fields on the infrared-sensitive membrane may explain
the behavioral performance of this sensory system. Our model explores the optical
quality of the infrared system by detailing how a functional representation of
the thermal properties of the environment can be created. The model is easy to
implement neuronally and agrees well with available neuronal, physiological, and
behavioral data on the snake infrared system.
PMID- 17026210
TI - Kinetics of the Wako-Saito-Munoz-Eaton model of protein folding.
AB - We consider a simplified model of protein folding, with binary degrees of
freedom, whose equilibrium thermodynamics is exactly solvable. Based on this
exact solution, the kinetics is studied in the framework of a local equilibrium
approach, for which we prove that (i) the free energy decreases with time, (ii)
the exact equilibrium is recovered in the infinite time limit, and (iii) the
equilibration rate is an upper bound of the exact one. The kinetics is compared
to the exact one for a small peptide and to Monte Carlo simulations for a longer
protein; then rates are studied for a real protein and a model structure.
PMID- 17026211
TI - Long-range depletion forces induced by associating small molecules.
AB - This is the first report of experimental observations of depletion interactions
in solutions of a (hydrogen-bonded) reversible supramolecular polymer. Depletion
forces were measured directly by colloidal probe atomic force microscopy. The
range of the depletion force is consistent with existing independent experimental
data. The interaction can be tuned by adding monofunctional chain stoppers to the
solution, a possibility which is unique to supramolecular polymers. The depletion
force is shown to be strong enough to induce phase separation in a colloidal
suspension.
PMID- 17026212
TI - Repulsion between oppositely charged surfaces in multivalent electrolytes.
AB - In answer to recent experimental force measurements between oppositely charged
surfaces we here reproduce the repulsion in the presence of multivalent salt
using Monte Carlo simulations within the primitive model. Our osmotic pressure
curves are in good agreement with experimental results. In contrast with Poisson
Boltzmann calculations, both repulsion and charge inversion are seen in the
simulations. Repulsion is observed only for conditions under which there is
charge inversion at large separations. However, in these cases, the repulsion is
present also at intermediate separations, where there is no charge inversion. The
charge inversion is thereby not the cause of the repulsion. Instead the repulsion
appears to be an effect of the large amount of excess salt in the slit. Both
phenomena, however, are closely linked and a consequence of ion-ion correlations,
promoted by a strong electrostatic coupling.
PMID- 17026213
TI - Spin decoherence in superconducting atom chips.
AB - Using a consistent quantum-mechanical treatment for the electromagnetic
radiation, we theoretically investigate the magnetic spin-flip scatterings of a
neutral two-level atom trapped in the vicinity of a superconducting body. We
derive a simple scaling law for the corresponding spin-flip lifetime for such an
atom trapped near a superconducting thick slab. For temperatures below the
superconducting transition temperature Tc, the lifetime is found to be enhanced
by several orders of magnitude in comparison to the case of a normal conducting
slab. At zero temperature the spin-flip lifetime is given by the unbounded free
space value.
PMID- 17026214
TI - Surface tension in unitary fermi gases with population imbalance.
AB - We study the effects of surface tension between normal and superfluid regions of
a trapped Fermi gas at unitarity. We find that surface tension causes notable
distortions in the shape of large aspect ratio clouds. Including these
distortions in our theories resolves many of the apparent discrepancies among
different experiments and between theory and experiments.
PMID- 17026215
TI - Controlled splitting of an atomic wave packet.
AB - We propose a simple scheme capable of adiabatically splitting an atomic wave
packet using two independent translating traps. Implemented with optical dipole
traps, our scheme allows a high degree of flexibility for atom interferometry
arrangements and highlights its potential as an efficient and high fidelity atom
optical beam splitter.
PMID- 17026216
TI - Released momentum distribution of a Fermi gas in the BCS-BEC crossover.
AB - We develop a time-dependent mean-field theory to investigate the released
momentum distribution and the released energy of an ultracold Fermi gas in the
BCS-BEC crossover after the scattering length has been set to zero by a fast
magnetic-field ramp. For a homogeneous gas we analyze the nonequilibrium dynamics
of the system as a function of the interaction strength and of the ramp speed.
For a trapped gas the theoretical predictions are compared with experimental
results.
PMID- 17026217
TI - AMANDA observations constrain the ultrahigh energy neutrino flux.
AB - A number of experimental techniques are currently being deployed in an effort to
make the first detection of ultrahigh energy cosmic neutrinos. To accomplish this
goal, techniques using radio and acoustic detectors are being developed, which
are optimally designed for studying neutrinos with energies in the PeV-EeV range
and above. Data from the AMANDA experiment, in contrast, have been used to place
limits on the cosmic neutrino flux at less extreme energies (up to approximately
10 PeV). In this Letter, we show that by adopting a different analysis strategy,
optimized for much higher energy neutrinos, the same AMANDA data can be used to
place a limit competitive with radio techniques at EeV energies. We also discuss
the sensitivity of the IceCube experiment, in various stages of deployment, to
ultrahigh energy neutrinos.
PMID- 17026218
TI - Stringent constraint on galactic positron production.
AB - The intense 0.511 MeV gamma-ray line emission from the Galactic Center observed
by INTEGRAL requires a large annihilation rate of nonrelativistic positrons. If
these positrons are injected at even mildly relativistic energies, higher-energy
gamma rays will also be produced. We calculate the gamma-ray spectrum due to
inflight annihilation and compare it with the observed diffuse Galactic gamma-ray
data. Even with a simplified but conservative treatment, we find that the
positron injection energies must be less than or similar to 3 MeV, which strongly
constrains models for Galactic positron production.
PMID- 17026219
TI - Can sterile neutrinos be ruled out as warm dark matter candidates?
AB - We present constraints on the mass of warm dark matter (WDM) particles from a
combined analysis of the matter power spectrum inferred from the Sloan Digital
Sky Survey Lyman-alpha flux power spectrum at 2.2n
massless processes for the first time at two loops. Using color-generator
notation, we show that it is proportional to the one-loop matrix. This result
reproduces all pole terms in dimensional regularization of the explicit
calculations of massless 2-->2 amplitudes in the literature, and it predicts all
poles at next-to-next-to-leading order in any 2-->n process that has been
computed at next-to-leading order. The proportionality of the one- and two-loop
matrices makes possible the resummation in closed form of the next-to-next-to
leading logarithms and poles in dimensional regularization for the 2-->n
processes.
PMID- 17026222
TI - Yang-mills magnetofluid unification.
AB - We generalize the hybrid magnetofluid model of a charged fluid interacting with
an electromagnetic field to the dynamics of a relativistic hot fluid interacting
with a non-Abelian field. The fluid itself is endowed with a non-Abelian charge
and the consequences of this generalization are worked out. Applications of this
formalism to the quark gluon plasma are suggested.
PMID- 17026223
TI - Island of rare Earth nuclei with tetrahedral and octahedral symmetries: possible
experimental evidence.
AB - Calculations using realistic mean-field methods suggest the existence of nuclear
shapes with tetrahedral Td and/or octahedral Oh symmetries sometimes at only a
few hundreds of keV above the ground states in some rare earth nuclei around
156Gd and 160Yb. The underlying single-particle spectra manifest exotic fourfold
rather than Kramers's twofold degeneracies. The associated shell gaps are very
strong, leading to a new form of shape coexistence in many rare earth nuclei. We
present possible experimental evidence of the new symmetries based on the
published experimental results--although an unambiguous confirmation will require
dedicated experiments.
PMID- 17026224
TI - High-resolution study of x-ray resonant Raman scattering at the K edge of
silicon.
AB - We report on the first high-resolution measurements of the K x-ray resonant Raman
scattering (RRS) in Si. The measured x-ray RRS spectra, interpreted using the
Kramers-Heisenberg approach, revealed spectral features corresponding to
electronic excitations to the conduction and valence bands in silicon. The total
cross sections for the x-ray RRS at the 1s absorption edge and the 1s-3p
excitation were derived. The Kramers-Heisenberg formalism was found to reproduce
quite well the x-ray RRS spectra, which is of prime importance for applications
of the total-reflection x-ray fluorescence technique.
PMID- 17026225
TI - Difference between a photon's momentum and an atom's recoil.
AB - When an atom absorbs a photon from a laser beam that is not an infinite plane
wave, the atom's recoil is less than variant Planck's k in the propagation
direction. We show that the recoils in the transverse directions produce a
lensing of the atomic wave functions, which leads to a frequency shift that is
not discrete but varies linearly with the field amplitude and strongly depends on
the atomic state detection. The same lensing effect is also important for
microwave atomic clocks. The frequency shifts are of the order of the naive
recoil shift for the transverse wave vector of the photons.
PMID- 17026226
TI - Deterministic and nondestructively verifiable preparation of photon number
states.
AB - An experimentally viable approach for preparing arbitrary photon number states of
a cavity mode using continuous measurement and real-time quantum feedback is
presented. The procedure passively monitors the number state actually achieved in
each feedback-stabilized measurement trajectory, thus providing nondestructively
verifiable photon generation. The feasibility of a possible cavity QED
implementation in the many-atom, good-cavity-coupling regime is analyzed.
PMID- 17026221
TI - Measurement of deeply virtual compton scattering with a polarized-proton target.
AB - The longitudinal target-spin asymmetry AUL for the exclusive electroproduction of
high-energy photons was measured for the first time in ep-->e;'pgamma. The data
have been accumulated at JLab with the CLAS spectrometer using 5.7 GeV electrons
and a longitudinally polarized NH3 target. A significant azimuthal angular
dependence was observed, resulting from the interference of the deeply virtual
Compton scattering and Bethe-Heitler processes. The amplitude of the sinvarphi
moment is 0.252+/-0.042stat+/-0.020sys. Theoretical calculations are in good
agreement with the magnitude and the kinematic dependence of the target-spin
asymmetry, which is sensitive to the generalized parton distributions H and H.
PMID- 17026227
TI - All-angle broadband negative refraction of metal waveguide arrays in the visible
range: theoretical analysis and numerical demonstration.
AB - In this Letter, we introduce a simple metal waveguide array for realizing all
angle wide frequency bandwidth negative refraction from the visible to infrared
frequencies. Theoretical analysis from the rigorous coupled-wave theory reveals
that the negative coupling constant resulting from the anomalous coupling of
guided surface plasmon polariton modes contributes to the negative refraction.
The analytical results are confirmed by finite-difference time-domain numerical
simulations. Our result provides an alternative way to construct robust all-angle
negative refractive materials operating in a wide range of frequency from the
near-infrared to the visible range.
PMID- 17026228
TI - Ambiguities in the scattering tomography for central potentials.
AB - Invisibility devices exploit ambiguities in the inverse scattering problem of
light in media. Scattering also serves as an important general tool to infer
information about the structure of matter. We elucidate the nature of scattering
ambiguities that arise in central potentials. We show that scattering is a
tomographic projection: The integrated scattering angle is a projection of a
scattering function onto the impact parameter. This function depends on the
potential but may be multivalued, allowing for ambiguities where several
potentials share the same scattering data. In addition, multivalued scattering
angles also lead to ambiguities. We apply our theory to show that it is, in
principle, possible to construct an invisibility device without infinite phase
velocity of light.
PMID- 17026229
TI - Controllable self-steepening of ultrashort pulses in quadratic nonlinear media.
AB - By analyzing ultrashort optical pulse propagation in quadratic nonlinear media
beyond the slowly varying envelope approximation, we find that the sign and
magnitude of self-steepening can be controlled through the wave vector mismatch.
As an example of this phenomenon's impact on ultrashort pulse propagation, we
show that it may be used to cancel the propagation effects of group-velocity
mismatch. We obtain quantitative agreement between theory, simulations, and
experiments.
PMID- 17026230
TI - Stable vortex tori in the three-dimensional cubic-quintic Ginzburg-Landau
equation.
AB - We demonstrate the existence of stable toroidal dissipative solitons with the
inner phase field in the form of rotating spirals, corresponding to vorticity
S=0, 1, and 2, in the complex Ginzburg-Landau equation with the cubic-quintic
nonlinearity. The stable solitons easily self-trap from pulses with embedded
vorticity. The stability is corroborated by accurate computation of growth rates
for perturbation eigenmodes. The results provide the first example of stable
vortex tori in a 3D dissipative medium, as well as the first example of higher
order tori (with S=2) in any nonlinear medium. It is found that all stable
vortical solitons coexist in a large domain of the parameter space; in smaller
regions, there coexist stable solitons with either S=0 and S=1, or S=1 and S=2.
PMID- 17026231
TI - Photonic crystal lens: from negative refraction and negative index to negative
permittivity and permeability.
AB - We consider a dielectric photonic crystal made of cylindrical holes in a high
index matrix. We show that a given finite size photonic crystal can mimic a
homogeneous material whose permittivity and permeability are negative. We pay
attention to the limitation of the homogeneous medium model and the vital role of
the truncation of the crystal.
PMID- 17026232
TI - Spatial four wave mixing in nonlinear periodic structures.
AB - We present the first experimental study of spatial four-wave mixing in photonic
lattices, demonstrating universal aspects of nonlinear processes in periodic
media, such as engineered phase matching, Bloch-wave folding, and continuous
control over the band at which the interaction products emerge.
PMID- 17026233
TI - Transport of magnetic field by a turbulent flow of liquid sodium.
AB - We study the effect of a turbulent flow of liquid sodium generated in the von
Karman geometry, on the localized field of a magnet placed close to the frontier
of the flow. We observe that the field can be transported by the flow on
distances larger than its integral length scale. In the most turbulent
configurations, the mean value of the field advected at large distance vanishes.
However, the rms value of the fluctuations increases linearly with the magnetic
Reynolds number. The advected field is strongly intermittent.
PMID- 17026234
TI - Bistability of a compliant cavity induced by acoustic radiation pressure.
AB - We report on the first observation of multiple-order bistability due to acoustic
radiation pressure in a compliant acoustic cavity formed between a spherical
ultrasonic transducer immersed in water and the free liquid surface located at
its focus. The hysteretic behavior of the cavity length, observed both with
amplitude ramps and frequency sweeps, is accurately described using a one
dimensional model of a compliant Fabry-Perot resonator assuming the acoustic
radiation pressure to be the only coupling between the cavity and the acoustic
field.
PMID- 17026235
TI - Femtosecond undulator radiation from sliced electron bunches.
AB - At the 1.7-GeV electron storage ring BESSY II, a first source of synchrotron
radiation with 100 fs pulse duration, variable (linear and circular)
polarization, tunable photon energy (300 to 1400 eV), and excellent signal-to
background ratio was constructed and is now in routine operation.
PMID- 17026236
TI - Laser seeding of the storage-ring microbunching instability for high-power
coherent terahertz radiation.
AB - We report the first observation of laser seeding of the storage-ring
microbunching instability. Above a threshold bunch current, the interaction of
the beam and its radiation results in a coherent instability, observed as a
series of stochastic bursts of coherent synchrotron radiation (CSR) at terahertz
frequencies initiated by fluctuations in the beam density. We have observed that
this effect can be seeded by imprinting an initial density modulation on the beam
by means of laser "slicing." In such a situation, most of the bursts of CSR
become synchronous with the pulses of the modulating laser and their average
intensity scales exponentially with the current per bunch. We present detailed
experimental observations of the seeding effect and a model of the phenomenon.
This seeding mechanism also creates potential applications as a high-power source
of CSR at terahertz frequencies.
PMID- 17026237
TI - Active-feedback control of the magnetic boundary for magnetohydrodynamic
stabilization of a fusion plasma.
AB - Stable operation with control on magnetohydrodynamic modes has been obtained in
the modified reversed field experiment employing a set of 192 feedback controlled
saddle coils. Improvements of plasma temperature, confinement (twofold), and
pulse length (threefold) and, as a consequence of the magnetic fluctuation
reduction, strong mitigation of plasma-wall interaction and mode locking are
reported.
PMID- 17026238
TI - Enhanced energy confinement and performance in a low-recycling tokamak.
AB - Extensive lithium wall coatings and liquid lithium plasma-limiting surfaces
reduce recycling, with dramatic improvements in Ohmic plasma discharges in the
Current Drive Experiment-Upgrade. Global energy confinement times increase by up
to 6 times. These results exceed confinement scalings such as ITER98P(y,1) by 2-3
times, and represent the largest increase in energy confinement ever observed for
an Ohmic tokamak plasma. Measurements of Dalpha emission indicate that global
recycling coefficients decrease to approximately 0.3, the lowest documented for a
magnetically confined hydrogen plasma.
PMID- 17026239
TI - Upstream ionization instability associated with a current-free double layer.
AB - A low frequency instability has been observed using various electrostatic probes
in a low-pressure expanding helicon plasma. The instability is associated with
the presence of a current-free double layer (DL). The frequency of the
instability increases linearly with the potential drop of the DL, and
simultaneous measurements show their coexistence. A theory for an upstream
ionization instability has been developed, which shows that electrons accelerated
through the DL increase the ionization upstream and are responsible for the
observed instability. The theory is in good agreement with the experimental
results.
PMID- 17026240
TI - Effect of external static magnetic field on the emittance and total charge of
electron beams generated by laser-Wakefield acceleration.
AB - Significant enhancement of emittance and an increase of the total charge of
femtosecond electron beams produced by a 12 TW, 40 fs laser pulse, tightly
focused in a He gas jet, are observed after applying a static magnetic field, B>
or =0.2 T, directed along the axis of laser pulse propagation. The effect appears
when plasma produced by a laser prepulse becomes magnetized in the vicinity of
the focus point: the electron Larmor frequency exceeds the collisional frequency,
while periphery of the plasma remains unmagnetized. The entailed change in the
shape of the plasma suppresses the diffraction of the main laser pulse that
results in a much higher charge of electrons self-injected during the
longitudinal wave breaking of the laser wake as well as the excellent stability
of the beams.
PMID- 17026241
TI - Critical Casimir force in 4He films: confirmation of finite-size scaling.
AB - We present new capacitance measurements of critical Casimir force-induced
thinning of 4He films near the superfluid transition, focused on the region below
Tlambda where the effect is the greatest. 4He films of 238, 285, and 340 A
thickness are adsorbed on atomically smooth, N-doped silicon substrates. The
Casimir force scaling function theta, deduced from the thinning of these three
films, collapses onto a single universal curve, attaining a minimum theta=-1.30+/
0.03 at x=td1/nu=-9.7+/-0.8 A1/nu. The collapse confirms the finite-size scaling
origin of the dip in the film thickness. Separately, we also confirm the presence
down to 2.13 K of the Goldstone or surface fluctuation force, which makes the
superfluid film approximately 2 A thinner than the normal film.
PMID- 17026242
TI - Kink formation and motion in carbon nanotubes at high temperatures.
AB - We report that kink motion is a universal plastic deformation mode in all carbon
nanotubes when being tensile loaded at high temperatures. The kink motion,
observed inside a high-resolution transmission electron microscope, is
reminiscent of dislocation motion in crystalline materials: namely, it
dissociates and multiplies. The kinks are nucleated from vacancy creation and
aggregation, and propagate in either a longitudinal or a spiral path along the
nanotube walls. The kink motion is related to dislocation glide and climb
influenced by external stress and high temperatures in carbon nanotubes.
PMID- 17026243
TI - Grain boundary transitions in binary alloys.
AB - A thermodynamic diffuse interface analysis predicts that grain boundary
transitions in solute absorption are coupled to localized structural order
disorder transitions. An example calculation of a planar grain boundary using a
symmetric binary alloy shows that first-order boundary transitions can be
predicted as a function of the crystallographic grain boundary misorientation and
empirical gradient coefficients. The predictions are compared to published
experimental observations.
PMID- 17026244
TI - Hydrogen-mediated nitrogen clustering in dilute III-V nitrides.
AB - First-principles calculation reveals multi-N clusters to be the ground states for
hydrogenated N in dilute III-V nitrides. While hydrogenation of a single N,
forming H2*(N), can relax the large strain induced by the size-mismatched N,
formation of the clusters will relax the strain even more effectively. This
suppresses the formation of H2*(N), the existence of which has recently been
debated. More importantly, postgrowth dehydrogenation of the N-H clusters
provides an explanation to the observed metastable bare N clusters in GaAsN grown
by gas-source molecular beam epitaxy or metal-organic chemical vapor deposition.
PMID- 17026245
TI - Hall-petch law revisited in terms of collective dislocation dynamics.
AB - The Hall-Petch (HP) law, that accounts for the effect of grain size on the
plastic yield stress of polycrystals, is revisited in terms of the collective
motion of interacting dislocations. Sudden relaxation of incompatibility stresses
in a grain triggers aftershocks in the neighboring ones. The HP law results from
a scaling argument based on the conservation of the elastic energy during such
transfers. The Hall-Petch law breakdown for nanometric sized grains is shown to
stem from the loss of such a collective behavior as grains start deforming by
successive motion of individual dislocations.
PMID- 17026246
TI - Dynamics and internal stress at the nanoscale related to unique thermomechanical
behavior in polymer nanocomposites.
AB - A small amount of alumina nanoparticles in polymethylmethacrylate causes a sharp
depression of the glass transition temperature (Tg) accompanied by a toughening
of the composite. We investigated this phenomenon using multispeckle x-ray photon
correlation spectroscopy. Measurements reveal a dynamic structure factor that has
the form exp[-(t/taua)beta], with beta greater than 1. We show for the first time
that beta(T) tracks the internal stress at the polymer-particle interface. The
internal stress, which we propose arises due to the entropic penalty that the
polymer faces in the presence of the nanoparticles, engenders temporally
heterogeneous dynamics. In the jammed glassy state, we show that the dominant
fast relaxation mode--taumax--aided by a weak dewetting interface relieves the
stress and follows the variations in Tg.
PMID- 17026247
TI - Nonlinear analysis of oscillatory indentation in elastic and viscoelastic solids.
AB - Determining the mechanical properties at micro- and nanometer length scales using
nanoindentation or atomic force microscopy is important to many areas of science
and engineering. Here we establish equations for obtaining storage and loss
modulus from oscillatory indentations by performing a nonlinear analysis of
conical and spherical indentation in elastic and viscoelastic solids. We show
that, when the conical indenter is driven by a sinusoidal force, the square of
displacement is a sinusoidal function of time, not the displacement itself, which
is commonly assumed. Similar conclusions hold for spherical indentations. Well
known difficulties associated with measuring contact area and correcting thermal
drift may be circumvented using the newly derived equations. These results may
help improve methods of using oscillatory indentation for determining elastic and
viscoelastic properties of solids.
PMID- 17026248
TI - Tuning of tetrahedrality in a silicon potential yields a series of monatomic
(metal-like) glass formers of very high fragility.
AB - We obtain monatomic glass formers in simulations by modifying the tetrahedral
character in a silicon potential to explore a triple point zone between
potentials favoring diamond (dc) and bcc crystals. dc crystallization is always
preceded by a polyamorphic transformation of the liquid, and is frustrated when
the Kauzmann temperature of the high temperature liquid intersects the liquid
liquid coexistence line. The glass forming liquids are extraordinarily fragile.
Our results suggest that Si and Ge liquids may be vitrified at a pressure close
to the diamond-beta-tin-liquid triple point.
PMID- 17026249
TI - Leakage of O2 precursor molecules from inert hydrogen islands on a Pt(111)
surface.
AB - We have observed, using infrared spectroscopy, that the precursor-mediated O2
chemisorption on the clean and the partially hydrogen-covered Pt(111) surfaces
exhibits opposite temperature dependencies above the temperature for stable O2
physisorption. While the chemisorption probability on the clean surface increases
with increasing temperature due to thermal activation of the precursor, it
decreases on the partially hydrogen-covered surface which we suggest is due to a
general loss of the mobile precursor molecules by thermal desorption from
chemically inert hydrogen islands.
PMID- 17026250
TI - In situ study of the growth of nanodots in organic heteroepitaxy.
AB - We report the self-organization of organic nanodots with high crystallinity
during the growth of organic heterostructures of Di-indenoperylene (DIP) onto
copper-hexadecafluorophthalocyanine (F16CuPc), donor and acceptor molecules,
respectively. The process is related to the Stranski-Krastanov growth mode, which
is accompanied by a novel type of structural reconstruction of the underlying
organic film. This reconstruction affects three monolayers adjacent to the
organic interface. In spite of the close resemblance to the formation of
semiconductor nanostructures for inorganic heteroepitaxy, the present results
conclusively demonstrate a distinctly different growth mechanism for organic
heteroepitaxy whose understanding demands further theoretical studies.
PMID- 17026251
TI - High friction from a stiff polymer using microfiber arrays.
AB - High dry friction requires intimate contact between two surfaces and is generally
obtained using soft materials with an elastic modulus less than 10 MPa. We
demonstrate that high-friction properties similar to rubberlike materials can
also be obtained using microfiber arrays constructed from a stiff thermoplastic
(polypropylene, 1 GPa). The fiber arrays have a smaller true area of contact than
a rubberlike material, but polypropylene's higher interfacial shear strength
provides an effective friction coefficient of greater than 5 at normal loads of 8
kPa. At the pressures tested, the fiber arrays showed more than an order of
magnitude increase in shear resistance compared to the bulk material. Unlike
softer materials, vertical fiber arrays of stiff polymer demonstrate no
measurable adhesion on smooth surfaces due to high tensile stiffness.
PMID- 17026252
TI - Dissipation-driven quantum phase transitions in a Tomonaga-Luttinger liquid
electrostatically coupled to a metallic gate.
AB - The dissipation induced by a metallic gate on the low-energy properties of
interacting 1D electron liquids is studied. As a function of the distance to the
gate, or the electron density in the wire, the system can undergo a quantum phase
transition from a Tomonaga-Luttinger liquid to two kinds of dissipative phases,
one of them with a finite spatial correlation length. We also define a dual
model, which describes an attractive one-dimensional metal with a Josephson
coupling to a dirty metallic lead.
PMID- 17026253
TI - Nonlinear magnetotransport in interacting chiral nanotubes.
AB - Nonlinear transport through interacting single-wall nanotubes containing a few
impurities is studied theoretically. Extending the Luttinger liquid theory to
incorporate trigonal warping and chirality effects, we derive the current
contribution Ie even in the applied voltage V and odd in an orbital magnetic
field B, which is nonzero only for chiral tubes and in the presence of
interactions.
PMID- 17026254
TI - Optically probing spin and charge interactions in a tunable artificial molecule.
AB - We optically probe and electrically control a single artificial molecule
containing a well defined number of electrons. Charge and spin dependent interdot
quantum couplings are probed optically by adding a single electron-hole pair and
detecting the emission from negatively charged exciton states. Coulomb- and Pauli
blockade effects are directly observed, and tunnel coupling and electrostatic
charging energies are independently measured. The interdot quantum coupling is
shown to be mediated by electron tunneling. Our results are in excellent accord
with calculations that provide a complete picture of negative excitons and few
electron states in quantum dot molecules.
PMID- 17026255
TI - Finite-size error in many-body simulations with long-range interactions.
AB - We discuss the origin of the finite-size error of the energy in many-body
simulation of systems of charged particles and we propose a correction based on
the random-phase approximation at long wavelengths. The correction is determined
mainly by the collective charge oscillations of the interacting system. Finite
size corrections, both on kinetic and potential energy, can be calculated within
a single simulation. Results are presented for the electron gas and silicon.
PMID- 17026256
TI - Continuous-time solver for quantum impurity models.
AB - We present a new continuous-time solver for quantum impurity models such as those
relevant to dynamical mean field theory. It is based on a stochastic sampling of
a perturbation expansion in the impurity-bath hybridization parameter.
Comparisons with Monte Carlo and exact diagonalization calculations confirm the
accuracy of the new approach, which allows very efficient simulations even at low
temperatures and for strong interactions. As examples of the power of the method
we present results for the temperature dependence of the kinetic energy and the
free energy, enabling an accurate location of the temperature-driven metal
insulator transition.
PMID- 17026257
TI - Spin cloud induced around an elastic scatterer by the intrinsic spin hall effect.
AB - Similar to the Landauer electric dipole created around an impurity by the
electric current, a spin polarized cloud of electrons can be induced by the
intrinsic spin Hall effect near a spin independent elastic scatterer. It is shown
that in the ballistic range around the impurity, such a cloud appears in the case
of Rashba spin-orbit interaction, even though the bulk spin Hall current is
absent.
PMID- 17026258
TI - Direct measurement of the singlet generation yield in polymer light-emitting
diodes.
AB - In this study, the singlet and triplet exciton generation yields of a
representative blue-emitting conjugated polymer are directly compared using
simultaneous optical and electrical excitation measurements. After carefully
accounting for bimolecular triplet annihilation and knowing the independently
measured solid state inter-system-crossing yield of the polymer, a singlet
generation yield of 44% is obtained, in the working device, which is clearly in
excess of the simple quantum statistical 25% limit.
PMID- 17026259
TI - Friedel sum rule for an interacting multiorbital quantum dot.
AB - A generalized Friedel sum rule is derived for a quantum dot with internal orbital
and spin degrees of freedom. The result is valid when all many-body correlations
are taken into account and it links the phase shift of the scattered electron to
the displacement of its spectral density into the dot.
PMID- 17026260
TI - Fractional charge revealed in computer simulations of resonant tunneling in the
fractional quantum Hall regime.
AB - The concept of fractional charge is central to the theory of the fractional
quantum Hall effect. Here I use exact diagonalization as well as configuration
space renormalization to study finite clusters which are large enough to contain
two independent edges. I analyze the conditions of resonant tunneling between the
two edges. The "computer experiment" reveals a periodic sequence of resonant
tunneling events consistent with the experimentally observed fractional
quantization of electric charge in units of e/3 and e/5.
PMID- 17026261
TI - Geometrical spin dephasing in quantum dots.
AB - We study spin-orbit mediated relaxation and dephasing of electron spins in
quantum dots. We show that higher order contributions provide a relaxation
mechanism that dominates for low magnetic fields and is of geometrical origin. In
the low-field limit relaxation is dominated by coupling to electron-hole
excitations and possibly 1/f noise rather than phonons.
PMID- 17026262
TI - Inelastic quantum transport and peierls-like mechanism in carbon nanotubes.
AB - We report on a theoretical study of inelastic quantum transport in (3m,0) carbon
nanotubes. By using a many-body description of the electron-phonon interaction in
Fock space, a novel mechanism involving optical phonon emission (absorption) is
shown to induce an unprecedented energy-gap opening at half the phonon energy,
variant Planck's over 2piomega0/2, above (below) the charge neutrality point.
This mechanism, which is prevented by Pauli blocking at low bias voltages, is
activated at bias voltages on the order of variant Planck's over 2piomega0.
PMID- 17026263
TI - Electrostatic force microscopy on oriented graphite surfaces: coexistence of
insulating and conducting behaviors.
AB - We present measurements of the electric potential fluctuations on the surface of
highly oriented pyrolytic graphite using electrostatic force and atomic force
microscopy. Micrometric domainlike potential distributions are observed even when
the sample is grounded. Such potential distributions are unexpected given the
good metallic conductivity of graphite because the surface should be an
equipotential. Our results indicate the coexistence of regions with
"metalliclike" and "insulatinglike" behaviors showing large potential
fluctuations of the order of 0.25 V. In lower quality graphite, this effect is
not observed. Experiments are performed in Ar and air atmospheres.
PMID- 17026264
TI - Kondo effect of an adsorbed cobalt phthalocyanine (CoPc) molecule: the role of
quantum interference.
AB - It has been shown that by distorting a CoPc molecule adsorbed on a Au(111)
surface a Kondo effect is induced with a temperature higher than 200 K. We
examine a model in which an atom with strong Coulomb repulsion (Co) is surrounded
by four atoms on a square (molecule lobes), with two atoms above and below it
representing the apex of the STM tip and an atom on the gold surface (all with a
single atomic orbital). The Hamiltonian is solved exactly for the isolated
cluster, and, after connecting the leads, the conductance is calculated by
standard techniques. Quantum interference prevents the existence of the Kondo
effect when the orbitals on the square do not interact (undistorted molecule);
the Kondo resonance shows up after switching on that interaction. The weight of
the Kondo resonance is controlled by the interplay of couplings to the STM tip
and the gold surface and between the molecule lobes.
PMID- 17026265
TI - Quantum two-level systems in Josephson junctions as naturally formed qubits.
AB - The two-level systems (TLSs) naturally occurring in Josephson junctions
constitute a major obstacle for the operation of superconducting phase qubits.
Since these TLSs can possess remarkably long decoherence times, we show that such
TLSs can themselves be used as qubits, allowing for a well controlled
initialization, universal sets of quantum gates, and readout. Thus, a single
current-biased Josephson junction can be considered as a multiqubit register. It
can be coupled to other junctions to allow the application of quantum gates to an
arbitrary pair of qubits in the system. Our results indicate an alternative way
to realize superconducting quantum information processing.
PMID- 17026266
TI - Onset of dendritic flux avalanches in superconducting films.
AB - We report a detailed comparison of experimental data and theoretical predictions
for the dendritic flux instability, believed to be a generic behavior of type-II
superconducting films. It is shown that a thermomagnetic model published very
recently [Phys. Rev. B 73, 014512 (2006)10.1103/PhysRevB.73.014512] gives an
excellent quantitative description of key features like the stability onset
(first dendrite appearance) magnetic field, and how the onset field depends on
both temperature and sample size. The measurements were made using magneto
optical imaging on a series of different strip-shaped samples of MgB2. Excellent
agreement is also obtained by reanalyzing data previously published for Nb.
PMID- 17026267
TI - Scanning tunneling spectroscopy on the novel superconductor CaC6.
AB - We present scanning tunneling microscopy and spectroscopy of the newly discovered
superconductor CaC6. The tunneling conductance spectra, measured between 3 and 15
K, show a clear superconducting gap in the quasiparticle density of states. The
gap function extracted from the spectra is in good agreement with the
conventional BCS theory with Delta0=1.6+/-0.2 meV. The possibility of gap
anisotropy and two-gap superconductivity is also discussed. In a magnetic field,
direct imaging of the vortices allows us to deduce a coherence length in the ab
plane xiab approximately 33 nm.
PMID- 17026268
TI - Coulomb blockade anisotropic magnetoresistance effect in a (Ga,Mn)As single
electron transistor.
AB - We observe low-field hysteretic magnetoresistance in a (Ga,Mn)As single-electron
transistor which can exceed 3 orders of magnitude. The sign and size of the
magnetoresistance signal are controlled by the gate voltage. Experimental data
are interpreted in terms of electrochemical shifts associated with magnetization
rotations. This Coulomb blockade anisotropic magnetoresistance is distinct from
previously observed anisotropic magnetoresistance effects as it occurs when the
anisotropy in a band structure derived parameter is comparable to an independent
scale, the single-electron charging energy. Effective kinetic-exchange model
calculations in (Ga,Mn)As show chemical potential anisotropies consistent with
experiment and ab initio calculations in transition metal systems suggest that
this generic effect persists to high temperatures in metal ferromagnets with
strong spin-orbit coupling.
PMID- 17026269
TI - First order phase transition in the frustrated triangular antiferromagnet
CsNiCl3.
AB - By means of high-resolution ultrasonic velocity measurements, as a function of
temperature and magnetic field, the nature of the different low temperatures
magnetic phase transitions observed for the quasi-one-dimensional compound
CsNiCl3 is established. Special attention has been devoted to the field-induced
120 degrees phase transition above the multicritical point in the H-T phase
diagram where the elastic constant C44 reveals a steplike variation and
hysteresis effects. These results represent the first experimental evidence that
the 120 degrees phase transition is weakly first order and contradict the popular
notion of new universality classes for chiral systems.
PMID- 17026270
TI - In-plane anisotropy of the electronic structure for the charge- and orbital
ordered state in half-doped manganite with layered structure.
AB - We report on the in-plane anisotropy of the electronic response in the spin-,
charge-, and orbital-ordered phase of a half-doped layered-structure manganite.
The optical conductivity spectra for a single domain of Eu1/2Ca3/2MnO4
unambiguously show the anisotropic charge dynamics which well corresponds to the
theoretical calculation: the optical conductivity with the polarization along the
zigzag ferromagnetic chain direction exhibits a smaller gap and a larger
intensity at lower energies than that of the perpendicular polarization mostly
due to the charge and orbital ordering and the associated quantum interference
effect.
PMID- 17026271
TI - Magnetic moment softening and domain wall resistance in Ni nanowires.
AB - We perform ab initio calculations of the electronic structure and conductance of
atomic-size Ni nanowires with domain walls only a few atomic lattice constants
wide. We show that the hybridization between noncollinear spin states leads to a
reduction of the magnetic moments in the domain wall resulting in the enhancement
of the domain wall resistance. Experimental studies of the magnetic moment
softening may be feasible with modern techniques such as scanning tunneling
spectroscopy.
PMID- 17026272
TI - Theoretical limit of the minimal magnetization switching field and the optimal
field pulse for Stoner particles.
AB - The theoretical limit of the minimal magnetization switching field and the
optimal field pulse design for uniaxial Stoner particles are investigated. Two
results are obtained. One is the existence of a theoretical limit of the smallest
magnetic field out of all possible designs. It is shown that the limit is
proportional to the damping constant in the weak damping regime and approaches
the Stoner-Wohlfarth (SW) limit at large damping. For a realistic damping
constant, this limit is more than 10 times smaller than that of so-called
precessional magnetization reversal under a noncollinear static field. The other
is on the optimal field pulse design: if the magnitude of a magnetic field does
not change, but its direction can vary during a reversal process, there is an
optimal design that gives the shortest switching time. The switching time depends
on the field magnitude, damping constant, and magnetic anisotropy.
PMID- 17026273
TI - Muon spin relaxation studies of superconductivity in a crystalline array of
weakly coupled metal nanoparticles.
AB - We report muon-spin-relaxation studies in weak transverse fields of the
superconductivity in the metal cluster compound, Ga84[N(SiMe3)2]20
Li6Br2(thf)20.2 toluene. The temperature and field dependence of the muon-spin
relaxation rate and Knight shift clearly evidence type II bulk superconductivity
below Tc approximately 7.8 K, with Bc1 approximately 0.06 T, Bc2 approximately
0.26 T, kappa approximately 2, and weak flux pinning. The data are well described
by the s-wave BCS model with weak electron-phonon coupling in the clean limit. A
qualitative explanation for the conduction mechanism in this novel type of narrow
band superconductor is presented.
PMID- 17026274
TI - Unclustering transition in freely cooling wet granular matter.
AB - The free cooling of one-dimensional wet granular matter is presented in the
framework of the minimal capillary model. We demonstrate analytically and by
extensive simulations that above a critical density, the clustering of wet
granular matter is not monotonic in time, but undergoes a sharp unclustering
transition. This precipitation of granular droplets out of the gas takes place
when the granular temperature comes close to the energy scale set by the
capillary interaction.
PMID- 17026275
TI - Morphometric approach to the solvation free energy of complex molecules.
AB - We show that the solvation free energy of a complex molecule such as a protein
can be calculated using only four geometrical measures of the molecular structure
and corresponding thermodynamical coefficients. We compare results from this
morphometric approach to those obtained by an elaborate statistical-mechanical
theory in liquid state physics for a large variety of different structures of
protein G and find excellent agreement. Since the computational time is
drastically reduced, the new approach provides a practical and efficient way for
calculating the solvation free energy which can be employed when this quantity
has to be calculated for a large number of structures, as in a simulation study
of protein folding.
PMID- 17026276
TI - Partial clustering in binary two-dimensional colloidal suspensions.
AB - Strongly interacting binary mixtures of superparamagnetic colloidal particles
confined to a two-dimensional water-air interface are examined by theory,
computer simulation, and experiment. The mixture exhibits a partial clustering in
equilibrium: in the voids of the matrix of unclustered big particles, the small
particles form subclusters with a spongelike topology which is accompanied by a
characteristic small-wave vector peak in the small-small structure factor. This
partial clustering is a general phenomenon occurring for strongly coupled
negatively nonadditive mixtures.
PMID- 17026277
TI - "Universal" distribution of interearthquake times explained.
AB - We propose a simple theory for the "universal" scaling law previously reported
for the distributions of waiting times between earthquakes. It is based on a
largely used benchmark model of seismicity, which just assumes no difference in
the physics of foreshocks, mainshocks, and aftershocks. Our theoretical
calculations provide good fits to the data and show that universality is only
approximate. We conclude that the distributions of interevent times do not reveal
more information than what is already known from the Gutenberg-Richter and the
Omori power laws. Our results reinforce the view that triggering earthquakes by
other earthquakes is a key physical mechanism to understand seismicity.
PMID- 17026278
TI - Comment on "scaling behavior of the Portevin-Le Chatelier effect in an Al-2.5% Mg
alloy".
PMID- 17026279
TI - Comment on "self-similar chain of metal nanospheres as an efficient nanolens".
PMID- 17026281
TI - Fate of vacancy-induced supersolidity in 4He.
AB - The supersolid state of matter, exhibiting nondissipative flow in solids, has
been elusive for 35 years. The recent discovery of a nonclassical moment of
inertia in solid 4He by Kim and Chan provided the first experimental evidence,
although the interpretation in terms of supersolidity of the ideal crystal phase
remains a subject to debate. Using quantum Monte Carlo methods we investigate the
long-standing question of vacancy-induced superflow and find that vacancies in a
4He crystal phase separate instead of forming a supersolid. On the other hand,
nonequilibrium vacancies relaxing on defects of polycrystalline samples could
provide an explanation for the experimental observations.
PMID- 17026282
TI - Environment-mediated control of a quantum system.
AB - Recently, a new approach for the controllability of a two-dimensional quantum
system S has been proposed, based on its interaction with an initially
uncorrelated two-dimensional probe P whose initial state can be arbitrarily
modified. Following this scheme and considering a particular model for the
environment, we show that, in some specific cases, the environment-induced
entanglement is rich enough to completely control the dynamics of S. Under
suitable conditions on the interaction of S, P, and the environment, we prove
that the state of S can be driven to an arbitrary target state by varying the
initial state of P.
PMID- 17026283
TI - Stable Skyrmions in spinor condensates.
AB - Globally symmetric spinor condensates in free space are argued not to support
stable topological defects in either two or three dimensions. In the latter case,
however, we show that a topological Skyrmion can be stabilized by forcing it to
adopt certain density profiles. A sufficient condition for the existence of
Skyrmion solutions in three dimensions is formulated and illustrated in simple
examples. Our results pertain to Bose-Einstein condensation in 87Rb.
PMID- 17026284
TI - Degenerate Bose-Fermi mixture of metastable atoms.
AB - We report the observation of simultaneous quantum degeneracy in a dilute gaseous
Bose-Fermi mixture of metastable atoms. Sympathetic cooling of helium-3 (fermion)
by helium-4 (boson), both in the lowest triplet state, allows us to produce
ensembles containing more than 10(6) atoms of each isotope at temperatures below
1 microK, and achieve a fermionic degeneracy parameter of T/TF = 0.45. Because of
their high internal energy, the detection of individual metastable atoms with
subnanosecond time resolution is possible, permitting the study of bosonic and
fermionic quantum gases with unprecedented precision. This may lead to metastable
helium becoming the mainstay of quantum atom optics.
PMID- 17026285
TI - Optimal entanglement criterion for mixed quantum states.
AB - We develop a strong and computationally simple entanglement criterion. The
criterion is based on an elementary positive map Phi which operates on state
spaces with even dimension N > or = 4. It is shown that Phi detects many
entangled states with a positive partial transposition (PPT) and that it leads to
a class of optimal entanglement witnesses. This implies that there are no other
witnesses which can detect more entangled PPT states. The map Phi yields a
systematic method for the explicit construction of high-dimensional manifolds of
bound entangled states.
PMID- 17026286
TI - Distinctive fluctuations in a confined geometry.
AB - Spurred by recent theoretical predictions [Phys. Rev. E 69, 035102(R)
(2004)10.1103/PhysRevE.69.035102; Surf. Sci. Lett. 598, L355
(2005)10.1016/j.susc.2005.09.023], we find experimentally using STM line scans
that the fluctuations of the step bounding a facet exhibit scaling properties
distinct from those of isolated steps or steps on vicinal surfaces. The
correlation functions go as t0.15 +/- 0.03 decidedly different from the t0.26 +/-
0.02 behavior for fluctuations of isolated steps. From the exponents, we
categorize the universality, confirming the prediction that the nonlinear term of
the Kardar-Parisi-Zhang equation, long known to play a central role in
nonequilibrium phenomena, can also arise from the curvature or potential
asymmetry contribution to the step free energy.
PMID- 17026287
TI - Scalar-field-dominated cosmology with a transient acceleration phase.
AB - A new cosmological scenario driven by a slow rolling homogeneous scalar field
whose exponential potential V(Phi) has a quadratic dependence on the field Phi in
addition to the standard linear term is discussed. The derived equation of state
for the field predicts a transient accelerating phase, in which the Universe was
decelerated in the past, began to accelerate at redshift z approximately 1, is
currently accelerated, but, finally, will return to a decelerating phase in the
future. This overall dynamic behavior is profoundly different from the standard
evolution of the cold dark matter model with a cosmological constant, and may
alleviate some conflicts in reconciling the idea of a dark-energy-dominated
universe with observables in String or M theory. Some theoretical predictions for
the present scalar field plus dark matter dominated stage are confronted with
cosmological observations in order to test the viability of the scenario.
PMID- 17026288
TI - Simultaneous measurement of ionization and scintillation from nuclear recoils in
liquid xenon for a dark matter experiment.
AB - We report the first measurements of the absolute ionization yield of nuclear
recoils in liquid xenon, as a function of energy and electric field. Independent
experiments were carried out with two dual-phase time-projection chamber
prototypes, developed for the XENON dark matter project. We find that the charge
yield increases with decreasing recoil energy, and exhibits only a weak field
dependence. These results are the first unambiguous demonstration of the
capability of dual-phase xenon detectors to discriminate between electron and
nuclear recoils down to 20 keV, a key requirement for a sensitive dark matter
search.
PMID- 17026289
TI - No-go theorem for k-essence dark energy.
AB - We demonstrate that if k-essence can solve the coincidence problem and play the
role of dark energy in the Universe, the fluctuations of the field have to
propagate superluminally at some stage. We argue that this implies that
successful k-essence models violate causality. It is not possible to define a
time ordered succession of events in a Lorentz invariant way. Therefore, k
essence cannot arise as a low energy effective field theory of a causal,
consistent high energy theory.
PMID- 17026290
TI - Measurement of the quark mixing parameter cos2phi1 using time-dependent Dalitz
analysis of B0 -->D[KS(0)pi + pi-]h0.
AB - We present a measurement of the angle phi1 of the Cabibbo-Kobayashi-Maskawa
unitarity triangle using a time-dependent Dalitz analysis of D-->KS(0)pi + pi-
decays produced in neutral B meson decay to a neutral D meson and a light meson
(B0-->D*h0). The method allows a direct extraction of 2phi1 and, therefore, helps
to resolve the ambiguity between 2phi1 and pi-2phi1 in the measurement of
sin2phi1. We obtain sin2phi1= 0.78 +/- 0.44 +/- 0.22 and cos2varphi1 = 1.87(-0.53
0.32)(+0.40 + 0.22). The sign of cos2phi1 is determined to be positive at 98.3%
C.L.
PMID- 17026292
TI - Threshold resummation in momentum space from effective field theory.
AB - Methods from soft-collinear effective theory are used to perform the threshold
resummation of Sudakov logarithms for the deep-inelastic structure function
F2(x,Q2) in the end-point region x-->1 directly in momentum space. An explicit
all-order formula is derived, which expresses the short-distance coefficient
function C in the convolution F2 = C multiply sign in circle phi q in terms of
Wilson coefficients and anomalous dimensions defined in the effective theory.
Contributions associated with the physical scales Q2 and Q2(1-x) are separated
from nonperturbative hadronic physics in a transparent way. A crucial ingredient
to the momentum-space resummation is the exact solution to the integro
differential evolution equation for the jet function, which is derived. The
methods developed in this Letter can be applied to many other hard QCD processes.
PMID- 17026293
TI - Unified picture for single transverse-spin asymmetries in hard-scattering
processes.
AB - Using lepton-pair production in hadron-hadron collisions as an example, we
explore the relation between two well-known mechanisms for single-transverse-spin
asymmetries in hard processes: twist-three quark-gluon correlations when the
pair's transverse momentum is large, q perpendicular >> Lambda QCD, and time
reversal-odd and transverse-momentum-dependent parton distributions when q
perpendicular is much less than the pair's mass. We find that, although the two
mechanisms each have their own domain of validity, they describe the same physics
in the kinematic region where they overlap. This unifies the two mechanisms and
imposes an important constraint on phenomenological studies.
PMID- 17026294
TI - Differential cross section and photon-beam asymmetry for the gamma n --> K+ Sigma
reaction at E gamma = 1.5-2.4 GeV.
AB - Differential cross sections and photon-beam asymmetries have been measured for
the gamma n --> K+ Sigma- and gamma p --> K+Sigma0 reactions separately using
liquid deuterium and hydrogen targets with incident linearly polarized photon
beams of E gamma = 1.5-2.4 GeV at 0.6 < cos ThetacmK< 1. The cross section ratio
of sigma K+ Sigma-/sigma K+ Sigma0, expected to be 2 on the basis of the isospin
1/2 exchange, is found to be close to 1. For the K+ Sigma- reaction, large
positive asymmetries are observed, indicating the dominance of K* exchange. The
large difference between the asymmetries for the K+ Sigma- and K+ Sigma0
reactions cannot be explained by simple theoretical considerations based on Regge
model calculations.
PMID- 17026296
TI - Discovery of 109Xe and 105Te: superallowed alpha decay near doubly magic 100Sn.
AB - Two new alpha emitters 109Xe and 105Te were identified through the observation of
the 109Xe --> 105Te --> 101Sn alpha-decay chain. The 109Xe nuclei were produced
in the fusion-evaporation reaction 54Fe(58Ni,3n)109Xe and studied using the
Recoil Mass Spectrometer at the Holifield Radioactive Ion Beam Facility. Two
transitions at Ealpha = 4062 +/- 7 keV and Ealpha = 3918 +/- 9 keV were
interpreted as the l = 2 and l = 0 transitions from the 7/2+ ground state in
109Xe (T1/2 = 13 +/- 2 ms) to the 5/2+ ground state and a 7/2+ excited state,
located at 150 +/- 13 keV in 105Te. The observation of the subsequent decay of
105Te marks the discovery of the lightest known alpha-decaying nucleus. The
measured transition energy Ealpha = 4703 +/- 5 keV and half-life T1/2 = 620 +/-
70 ns were used to determine the reduced alpha-decay width delta2. The ratio
delta105Te(2)/delta213Po(2) of approximately 3 indicates a superallowed character
of the alpha emission from 105Te.
PMID- 17026297
TI - K isomers in 254No: probing single-particle energies and pairing strengths in the
heaviest nuclei.
AB - We have identified two isomers in 254No, built on two- and four-quasiparticle
excitations, with quantum numbers K pi = 8- and (14+), as well as a low-energy 2
quasiparticle Kpi = 3+ state. The occurrence of isomers establishes that K is a
good quantum number and therefore that the nucleus has an axial prolate shape.
The 2-quasiparticle states probe the energies of the proton levels that govern
the stability of superheavy nuclei, test 2-quasiparticle energies from theory,
and thereby check their predictions of magic gaps.
PMID- 17026298
TI - In-plane theory of nonsequential triple ionization.
AB - We describe first-principles in-plane calculations of nonsequential triple
ionization of atoms in a linearly polarized intense laser pulse. In a fully
classically correlated description, all three electrons respond dynamically to
the nuclear attraction, the pairwise e-e repulsions, and the laser force
throughout the duration of a 780 nm laser pulse. Nonsequential ejection is shown
to occur in a multielectron, possibly multicycle and multidimensional,
rescattering sequence that is coordinated by a number of sharp transverse
recollimation impacts.
PMID- 17026299
TI - Stark shift control of single optical centers in diamond.
AB - Lifetime-limited optical excitation lines of single nitrogen-vacancy (NV) defect
centers in diamond have been observed at liquid helium temperature. They display
unprecedented spectral stability over many seconds and excitation cycles.
Spectral tuning of the spin-selective optical resonances was performed via the
application of an external electric field (i.e., the Stark shift). A rich variety
of Stark shifts were observed including linear as well as quadratic components.
The ability to tune the excitation lines of single NV centers has potential
applications in quantum information processing.
PMID- 17026300
TI - Dipole blockade at Forster resonances in high resolution laser excitation of
Rydberg states of cesium atoms.
AB - High resolution laser excitation of np Rydberg states of cesium atoms shows a
dipole blockade at Forster resonances corresponding to the resonant dipole-dipole
energy transfer of the np+np --> ns+(n+1)s reaction. The dipole-dipole
interaction can be tuned on and off by the Stark effect, and such a process,
observed for relatively low n(25-41), is promising for quantum gate devices. Both
Penning ionization and saturation in the laser excitation can limit the range of
observation of the dipole blockade.
PMID- 17026301
TI - Controlling electronic spin relaxation of cold molecules with electric fields.
AB - We present a theoretical study of atom-molecule collisions in superimposed
electric and magnetic fields and show that dynamics of electronic spin relaxation
in molecules at temperatures below 0.5 K can be manipulated by varying the
strength and the relative orientation of the applied fields. The mechanism of
electric field control of Zeeman transitions is based on an intricate interplay
between intramolecular spin-rotation couplings and molecule-field interactions.
We suggest that electric fields may affect chemical reactions through inducing
nonadiabatic spin transitions and facilitate evaporative cooling of molecules in
a magnetic trap.
PMID- 17026302
TI - X-ray microprobe of orbital alignment in strong-field ionized atoms.
AB - We have developed a synchrotron-based, time-resolved x-ray microprobe to
investigate optical strong-field processes at intermediate intensities (10(14) -
10(15) W/cm2). This quantum-state specific probe has enabled the direct
observation of orbital alignment in the residual ion produced by strong-field
ionization of krypton atoms via resonant, polarized x-ray absorption. We found
strong alignment to persist for a period long compared to the spin-orbit coupling
time scale (6.2 fs). The observed degree of alignment can be explained by models
that incorporate spin-orbit coupling. The methodology is applicable to a wide
range of problems.
PMID- 17026303
TI - Cooling to the ground state of axial motion for one atom strongly coupled to an
optical cavity.
AB - Localization to the ground state of axial motion is demonstrated for a single,
trapped atom strongly coupled to the field of a high finesse optical resonator.
The axial atomic motion is cooled by way of coherent Raman transitions on the red
vibrational sideband. An efficient state detection scheme enabled by strong
coupling in cavity QED is used to record the Raman spectrum, from which the state
of atomic motion is inferred. We find that the lowest vibrational level of the
axial potential with zero-point energy variant Planck's over 2 h omega a/2kB = 13
microK is occupied with probability P0 approximately 0.95.
PMID- 17026304
TI - Light diffraction by a strong standing electromagnetic wave.
AB - The nonlinear quantum interaction of a linearly polarized x-ray probe beam with a
focused intense standing laser wave is studied theoretically. Because of the
tight focusing of the standing laser pulse, diffraction effects arise for the
probe beam as opposed to the corresponding plane wave scenario. A quantitative
estimate for realistic experimental conditions of the ellipticity and the
rotation of the main polarization plane acquired by the x-ray probe after the
interaction shows that the implementation of such vacuum effects is feasible with
future X-ray Free Electron Laser light.
PMID- 17026305
TI - Generation of a superposition of odd photon number states for quantum information
networks.
AB - We report on the experimental observation of quantum-network-compatible light
described by a nonpositive Wigner function. The state is generated by photon
subtraction from a squeezed vacuum state produced by a continuous wave optical
parametric amplifier. Ideally, the state is a coherent superposition of odd
photon number states, closely resembling a superposition of weak coherent states
|alpha > - |-alpha >. In the limit of low squeezing the state is basically a
single photon state. Light is generated with about 10,000 and more events per
second in a nearly perfect spatial mode with a Fourier-limited frequency
bandwidth which matches well atomic quantum memory requirements. The generated
state of light is an excellent input state for testing quantum memories, quantum
repeaters, and linear optics quantum computers.
PMID- 17026291
TI - Search for a neutral Higgs boson decaying to a W boson pair in pp collisions at
square root of s = 1.96 TeV.
AB - We present the results of a search for standard model Higgs boson production with
decay to WW*, identified through the leptonic final states e+ e- nu nu,+/-mu
/+nu nu and mu+ mu- nu nu. This search uses 360 pb -1 of data collected from pp
collisions at square root of s =1.96 TeV by the upgraded Collider Detector at
Fermilab (CDF II). We observe no signal excess and set 95% confidence level upper
limits on the production cross section times branching ratio for the Higgs boson
to WW* or any new scalar particle with similar decay products. These upper limits
range from 5.5 to 3.2 pb for Higgs boson masses between 120 and 200 GeV/c2.
PMID- 17026306
TI - Observation of surface gap solitons in semi-infinite waveguide arrays.
AB - We report on the observation of surface gap solitons found to exist at the
interface between uniform and periodic dielectric media with defocusing
nonlinearity. We demonstrate strong self-trapping at the edge of a LiNbO3
waveguide array and the formation of staggered surface solitons with propagation
constant inside the first photonic band gap. We study the crossover between
linear repulsion and nonlinear attraction at the surface, revealing the mechanism
of nonlinearity-mediated stabilization of the surface gap modes.
PMID- 17026307
TI - Model system for a one-dimensional magnetic photonic crystal.
AB - We fabricate and characterize one-dimensional magnetic (rather than dielectric)
photonic crystals for the first time. Our model system is a one-dimensional
periodic lattice of gold-wire pairs. Each pair can be viewed as a magnetic coil
with two slits and represents a "magnetic atom." Strong coupling between the
resulting magnetic-dipole resonance and the Bragg resonance is accomplished by an
adjacent dielectric slab waveguide, giving rise to an avoided crossing at near
infrared wavelengths. Our experimental findings are in excellent agreement with
theory.
PMID- 17026308
TI - Experimental detection of the optical Pendellosung effect.
AB - We report observations of periodic oscillatory behavior of the angular
selectivity, near the Bragg angle, in volume holographic gratings recorded in a
new photopolymerizable glass with high refractive index modulation. We have
detected the presence of overmodulation in the intensity distribution of the
first diffraction order. The results reported here were achieved by incorporating
in the photopolymerizable sol-gel glass zirconium-based high refractive index
species at the molecular level. This is the first time that this effect is
observed for light diffraction in an amorphous material.
PMID- 17026309
TI - Single-shot spectrometry for x-ray free-electron lasers.
AB - An experimental scheme to realize single-shot spectrometry for the diagnostics of
x-ray free-electron lasers (XFELs) is presented. The combination of an
ultraprecisely figured mirror and a perfect crystal form a simple, high-precision
spectrometer that can cover an energy range from a few eV to a hundred eV with
high resolution. The application of the spectrometer to determine XFEL pulse
widths was investigated theoretically and experimentally. It has been shown that
the present system can determine pulse widths from sub-fs to ps in a single shot
even for spontaneous radiation. The system can be easily extended to even shorter
pulses.
PMID- 17026310
TI - Relativistic AC gyromagnetic effects in ultraintense laser-matter interaction.
AB - We demonstrate that in ultraintense ultrafast laser-matter interaction, the
interplay of laser-induced oscillating space-charge fields with laser E and B
fields can strongly affect whether the interaction is relativistic or not:
stronger laser fields may not in fact produce more relativistic plasma
interactions. We show that there exists a regime of interaction, in the relation
of laser intensity and incident angle, for which the Brunel effect of electron
acceleration is strongly suppressed by AC gyromagnetic fields, at a frequency
different from the laser field. Analytically and with 1.5D particle-in-cell
modeling, we show that from gyromagnetic effects, even in the absence of usual J
x B second-harmonic contributions, there are strong effects on the harmonic
emission and on the generation of attosecond pulses.
PMID- 17026311
TI - Zonal flows in tokamak plasmas with toroidal rotation.
AB - Zonal flows in tokamak plasmas with toroidal rotation are theoretically
investigated. It is found that the low-frequency branch of zonal flows, which is
linearly stable in a nonrotating system, becomes linearly unstable in a rotating
tokamak, and that the high-frequency branch of zonal flows, the geodesic acoustic
mode, can propagate in the poloidal direction with the frequency significantly
lower than the frequency of the standing wave geodesic acoustic mode in the
nonrotating system.
PMID- 17026312
TI - Forced magnetic reconnection and field penetration of an externally applied
rotating helical magnetic field in the TEXTOR tokamak.
AB - The magnetic field penetration process into a magnetized plasma is of basic
interest both for plasma physics and astrophysics. In this context special
measurements on the field penetration and field amplification are performed by a
Hall probe on the dynamic ergodic divertor (DED) on the TEXTOR tokamak and the
data are interpreted by a two-fluid plasma model. It is observed that the growth
of the forced magnetic reconnection by the rotating DED field is accompanied by a
change of the plasma fluid rotation. The differential rotation frequency between
the DED field and the plasma plays an important role in the process of the
excitation of tearing modes. The momentum input from the rotating DED field to
the plasma is interpreted by both a ponderomotive force at the rational surface
and a radial electric field modified by an edge ergodization.
PMID- 17026295
TI - Measurement of the tt production cross section in pp collisions at square root of
s = 1.96 TeV.
AB - We present a measurement of the top quark pair production cross section in pp
collisions at square root of s = 1.96 TeV using 318 pb(-1) of data collected with
the Collider Detector at Fermilab. We select tt[over ] decays into the final
states enu+jets and mu nu+ jets, in which at least one b quark from the t-quark
decays is identified using a secondary vertex-finding algorithm. Assuming a top
quark mass of 178 GeV/c2, we measure a cross section of 8.7 +/- 0.9(stat)(
0.9)+1.1(syst) pb. We also report the first observation of tt[over ] with
significance greater than 5sigma in the subsample in which both b quarks are
identified, corresponding to a cross section of 10.1(-1.4)+1.6(stat)(
1.3)+2.0(syst) pb.
PMID- 17026313
TI - Anomalous ion channeling in AlInN/GaN bilayers: determination of the strain
state.
AB - Monte Carlo simulations of anomalous ion channeling in near-lattice-matched
AlInN/GaN bilayers allow an accurate determination of the strain state of AlInN
by Rutherford backscattering or channeling. Although these strain estimates agree
well with x-ray diffraction (XRD) results, XRD composition estimates are shown to
have limited accuracy, due to a possible deviation from Vegard's law, which we
quantify for this alloy. As the InN fraction increases from 13% to 19%, the
strain in AlInN films changes from tensile to compressive with lattice matching
predicted to occur at [InN] = 17.1%.
PMID- 17026314
TI - Low frequency Raman scattering from acoustic phonons confined in ZnO
nanoparticles.
AB - We report here the first observation of the low frequency Raman scattering from
acoustic phonons in semiconducting zinc oxide (ZnO) nanoparticles without
embedding in any solid matrix. ZnO nanoparticles (size 5-10 nm) with nearly
spherical shape have been synthesized using a chemical route. A shift in the
phonon peaks toward higher frequencies along with broadening was observed with a
decrease in particle size. The size dependence of the acoustic phonons in ZnO
nanoparticles is explained using Lamb's theory that predicts the vibrational
frequencies of a homogeneous elastic body of spherical shape. Our results show
that the observed low frequency Raman scattering originates from the spherical (l
= 0) and quadrupolar vibrations (l = 2) of the spheroidal mode due to the
confinement of acoustic vibrations in ZnO nanoparticles.
PMID- 17026316
TI - Isotope effect on the thermal conductivity of boron nitride nanotubes.
AB - We have measured the temperature-dependent thermal conductivity kappa(T) of
individual multiwall boron nitride nanotubes using a microfabricated test fixture
that allows direct transmission electron microscopy characterization of the tube
being measured. kappa(T) is exceptionally sensitive to isotopic substitution,
with a 50% enhancement in kappa(T) resulting for boron nitride nanotubes with
99.5% 11B. For isotopically pure boron nitride nanotubes, kappa rivals that of
carbon nanotubes of similar diameter.
PMID- 17026315
TI - O8 cluster structure of the epsilon phase of solid oxygen.
AB - Despite many experimental and theoretical studies, the crystal structure of the
epsilon phase of solid oxygen has not been determined. We performed powder x-ray
diffraction experiments and the Rietveld analyses in this study to show that a
new arrangement of the monoclinic space group C2/m could fit the diffraction
patterns of the epsilon phase and obtained a structure that consisted of an O8
cluster with 4 molecules. The dependence of the lattice parameters, the molar
volume, and the intermolecular distances on the pressure was investigated.
PMID- 17026317
TI - What controls deposition rate in electron-beam chemical vapor deposition?
AB - The key physical processes governing electron-beam-assisted chemical vapor
deposition are analyzed via a combination of theoretical modeling and supporting
experiments. The scaling laws that define growth of the nanoscale deposits are
developed and verified using carefully designed experiments of carbon deposition
from methane onto a silicon substrate. The results suggest that the chamber-scale
continuous transport of the precursor gas is the rate controlling process in
electron-beam chemical vapor deposition.
PMID- 17026318
TI - Superhard nitride-based nanocomposites: role of interfaces and effect of
impurities.
AB - Recently, a hardness similar to that of diamond has been reported for a
quasiternary, nitride-based nanocomposite. The related, quasibinary nanocomposite
"nc-TiN/a-Si3N4," which may be regarded as the prototype of the family of
superhard nc-metal-N/a-Si3N4 systems, also exhibits a significant hardness
enhancement. Extensive density-functional theory calculations indicate that the
superhardness is related to the preferential formation of TiN(111) polar
interfaces with a thin beta-Si3N4-derived layer. The strength of TiN in the 111
direction is similar to that of the weakest bonding direction in diamond. Oxygen
impurities cause a significant reduction of the interface strength.
PMID- 17026319
TI - Multiregional hybrid method and its application: formation of an atomic
protrusion at an atomic force microscope tip apex.
AB - We present a multiregional hybrid scheme which incorporates first-principles
(FP), tight-binding (TB), and molecular mechanical calculations. The key to this
hybrid scheme is to find an explicit description of the FP-TB region coupling. We
apply it to the atomic structure of a clean silicon atomic force microscope tip,
and find the formation of a distinct atomic protrusion at the tip apex. The
present study gives the reason why the atomic protrusion exits at the apex
despite the fact that the atomic geometry of the very end of the tip is
practically uncontrollable in the tip preparation.
PMID- 17026320
TI - Magnetically mediated transparent conductors: In2O3 doped with Mo.
AB - First-principles band structure investigations of the electronic, optical, and
magnetic properties of Mo-doped In2O3 reveal the vital role of magnetic
interactions in determining both the electrical conductivity and the Burstein
Moss shift which governs optical absorption. We demonstrate the advantages of the
transition metal doping which results in smaller effective mass, larger
fundamental band gap, and better overall optical transmission in the visible as
compared to commercial Sn-doped In2O3. Similar behavior is expected upon doping
with other transition metals opening up an avenue for the family of efficient
transparent conductors mediated by magnetic interactions.
PMID- 17026321
TI - Fractional shot noise in the kondo regime.
AB - Transport through quantum dots in the Kondo regime obeys an effective low
temperature theory in terms of weakly interacting quasiparticles. Despite the
weakness of the interaction, we find that the backscattering current and hence
the shot noise are dominated by two-quasiparticle scattering. We show that the
simultaneous presence of one- and two-quasiparticle scattering results in a
universal average charge 5/3e as measured by shot-noise experiments. An
experimental verification of our prediction would constitute a most stringent
test of the low-energy theory of the Kondo effect.
PMID- 17026322
TI - Spin-dependent quasiparticle transport in aluminum single-electron transistors.
AB - We investigate the effect of Zeeman splitting on quasiparticle transport in
normal-superconducting-normal (NSN) aluminum single-electron transistors (SETs).
In the above-gap transport, the interplay of Coulomb blockade and Zeeman
splitting leads to spin-dependence of the sequential tunneling. This creates
regimes where either one or both spin species can tunnel onto or off the island.
At lower biases, spin-dependence of the single quasiparticle state is studied,
and operation of the device as a bipolar spin filter is suggested.
PMID- 17026323
TI - Extreme ultrafast dynamics of quasiparticles excited in surface electronic bands.
AB - We develop a many-body description of the nonadiabatic dynamics of quasiparticles
in surface bands valid on an extremely ultrashort time scale by combining the
formalism for the calculation of quasiparticle survival probabilities with the
self-consistent treatment of the electronic response of the system. Applying this
approach to the benchmark Cu(111) surface, we assess the behavior and intervals
of preasymptotic electron and hole dynamics in surface bands and locate the
transition to the asymptotic regime of the exponential quasiparticle decay
characterized by the corrected Fermi golden rule-type of transition rate. The
general validity of these findings enables distinguishing the various regimes of
ultrafast electron dynamics that may be revealed in time resolved experiments.
PMID- 17026324
TI - Crossed Andreev reflection-induced magnetoresistance.
AB - We show that very large negative magnetoresistance can be obtained in magnetic
trilayers in a current-in-plane geometry owing to the existence of crossed
Andreev reflection. This spin valve consists of a thin superconducting film
sandwiched between two ferromagnetic layers whose magnetization is allowed to be
either parallelly or antiparallelly aligned. For a suitable choice of structure
parameters and nearly fully spin-polarized ferromagnets, the magnetoresistance
can exceed -80%. Our results are relevant for the design and implementation of
spintronic devices exploiting ferromagnet-superconductor structures.
PMID- 17026325
TI - First-principles periodic calculation of four-body spin terms in high-Tc cuprate
superconductors.
AB - A general mapping between the energy of pertinent magnetic solutions and the
diagonal terms of the spin Hamiltonian in a local representation provides the
first general framework to extract accurate values for the many body terms of
extended spin Hamiltonians from periodic first-principle calculations. Estimates
of these terms for La2CuO4, the paradigm of high-Tc superconductor parent
compounds, and for the SrCu2O3 ladder compound are reported. For La2CuO4, present
results support experimental evidence by Toader et al. [Phys. Rev. Lett. 94,
197202 (2005)10.1103/PhysRevLett.94.197202]. For SrCu2O3 even larger four-body
spin amplitudes are found together with Jl/Jr = 1 and non-negligible
ferromagnetic interladder exchange.
PMID- 17026326
TI - Highly spin-polarized field emissions induced by quantum size effects in
ultrathin films of Fe on W(001).
AB - Spin-polarized field emissions from Fe pseudomorphic ultrathin films on W(001)
surfaces are studied by density functional calculations. We found that nearly
completely spin-polarized field emission currents can be realized in two and four
Fe layers on W(001) and that these systems have the additional advantages of
thermal stability and low work functions. The unusually high spin polarizations
of the field emission current is traced to the Fe film's quantum size effects
leading to spin-polarized quantum well states and surface resonance states.
PMID- 17026327
TI - Absence of magnetism in hcp iron-nickel at 11 K.
AB - Synchrotron Mossbauer spectroscopy (SMS) was performed on an hcp-phase alloy of
composition Fe92Ni8 at a pressure of 21 GPa and a temperature of 11 K. Density
functional theoretical calculations predict antiferromagnetism in both hcp Fe and
hcp Fe-Ni. For hcp Fe, these calculations predict no hyperfine magnetic field,
consistent with previous experiments. For hcp Fe-Ni, however, substantial
hyperfine magnetic fields are predicted, but these were not observed in the SMS
spectra. Two possible explanations are suggested. First, small but significant
errors in the generalized gradient approximation density functional may lead to
an erroneous prediction of magnetic order or of erroneous hyperfine magnetic
fields in antiferromagnetic hcp Fe-Ni. Alternately, quantum fluctuations with
periods much shorter than the lifetime of the nuclear excited state would
prohibit the detection of moments by SMS.
PMID- 17026328
TI - Ultrahigh frequency nanotube resonators.
AB - We report carbon-nanotube-based electromechanical resonators with the fundamental
mode frequency over 1.3 GHz, operated in air at room temperature. A new
combination of drive and detection methods allows for unprecedented measurement
of both oscillation amplitude and phase and elucidates the relative mobility of
static charges near the nanotube. The resonator serves as an exceptionally
sensitive mass detector capable of approximately 10(-18) g resolution.
PMID- 17026329
TI - Spin-driven phonon splitting in bond-frustrated ZnCr2S4.
AB - Magnetic susceptibility, specific heat, thermal expansion, and IR spectroscopy
provide experimental evidence that the two subsequent antiferromagnetic
transitions in ZnCr2S4 at TN1 = 15 K and TN2 = 8 K are accompanied by significant
thermal and phonon anomalies. The anomaly at TN2 reveals a temperature hysteresis
typical for a first-order transformation. Because of strong spin-phonon coupling,
both magnetic transitions at TN1 and TN2 induce a splitting of phonon modes. The
anomalies and phonon splitting observed at TN2 are suppressed by strong magnetic
field. Regarding the small positive Curie-Weiss temperature Theta approximately 8
K, we argue that this scenario of two different magnetic phases with different
magnetoelastic couplings results from the strong competition of ferromagnetic and
antiferromagnetic exchange.
PMID- 17026330
TI - Quadrupolar phases of the s=1 bilinear-biquadratic Heisenberg model on the
triangular lattice.
AB - Using mean-field theory, exact diagonalizations, and SU(3) flavor theory, we have
precisely mapped out the phase diagram of the S = 1 bilinear-biquadratic
Heisenberg model on the triangular lattice in a magnetic field, with emphasis on
the quadrupolar phases and their excitations. In particular, we show that
ferroquadrupolar order can coexist with short-range helical magnetic order, and
that the antiferroquadrupolar phase is characterized by a remarkable 2/3
magnetization plateau, in which one site per triangle retains quadrupolar order
while the other two are polarized along the field. Implications for actual S=1
magnets are discussed.
PMID- 17026331
TI - Electrical measurement of spin-wave interactions of proximate spin transfer
nanooscillators.
AB - We have investigated the interaction mechanism between two nanocontact spin
transfer oscillators made on the same magnetic spin valve multilayer. The
oscillators phase lock when their precession frequencies are made similar, and a
giant magnetoresistance signal is detectable at one contact due to precession at
the other. Cutting the magnetic mesa between the contacts with a focused-ion beam
modifies the contact outputs, eliminates the phase locking, and strongly
attenuates the magnetoresistance coupling, which indicates that spin waves rather
than magnetic fields are the primary interaction mechanism.
PMID- 17026332
TI - Zeeman effect in superconducting two-leg ladders: irrational magnetization
plateaus and exceeding the Pauli limit.
AB - The effect of a parallel magnetic field on superconducting two-leg ladders is
investigated numerically. The magnetization curve displays an irrational plateau
at a magnetization equal to the hole density. Remarkably, its stability is
fundamentally connected to the existence of a well-known magnetic resonant mode.
Once the zero-field spin gap is suppressed by the field, pairs acquire a finite
momentum characteristic of a Fulde-Ferrell-Larkin-Ovchinnikov phase. In addition,
Sz = 0 triplet superconducting correlations coexist with singlet ones above the
irrational plateau. This provides a simple mechanism in which the Pauli limit is
exceeded as suggested by recent experiments.
PMID- 17026333
TI - Impurity band conduction in a high temperature ferromagnetic semiconductor.
AB - The band structure of a prototypical dilute magnetic semiconductor (DMS), Ga1
xMnxAs, is studied across the phase diagram via infrared and optical
spectroscopy. We prove that the Fermi energy (EF) resides in a Mn-induced
impurity band (IB). Specifically the changes in the frequency dependent optical
conductivity [sigma1(omega)] with carrier density are only consistent with EF
lying in an IB. Furthermore, the large effective mass (m*) of the carriers
inferred from our analysis of sigma1(omega) supports this conclusion. Our
findings demonstrate that the metal to insulator transition in this DMS is
qualitatively different from other III-V semiconductors doped with nonmagnetic
impurities. We also provide insights into the anomalous transport properties of
Ga1-xMnxAs.
PMID- 17026334
TI - Supersolid phases in the one-dimensional extended soft-core bosonic Hubbard
model.
AB - We present results of quantum Monte Carlo simulations for the soft-core extended
bosonic Hubbard model in one dimension exhibiting the presence of supersolid
phases similar to those recently found in two dimensions. We find that in one and
two dimensions, the insulator-supersolid transition has dynamic critical exponent
z = 2 whereas the first order insulator-superfluid transition in two dimensions
is replaced by a continuous transition with z = 1 in one dimension. We present
evidence that this transition is in the Kosterlitz-Thouless universality class
and discuss the mechanism behind this difference. The simultaneous presence of
two types of quasi-long-range order results in two solitonlike dips in the
excitation spectrum.
PMID- 17026335
TI - First-principles theory of quantum well resonance in double barrier magnetic
tunnel junctions.
AB - Quantum well (QW) resonances in Fe(001)/MgO/Fe/MgO/Fe double barrier magnetic
tunnel junctions are calculated from first principles. By including the Coulomb
blockade energy due to the finite size islands of the middle Fe film, we confirm
that the oscillatory differential resistance observed in a recent experiment [T.
Nozaki, Phys. Rev. Lett. 96, 027208 (2006)10.1103/PhysRevLett.96.027208]
originates from the QW resonances from the Delta1 band of the Fe majority-spin
channel. The primary source of smearing at low temperatures is shown to be the
variation of the Coulomb blockade energy.
PMID- 17026336
TI - Polarization and readout of coupled single spins in diamond.
AB - We study the coupling of a single nitrogen-vacancy center in diamond to a nearby
single nitrogen defect at room temperature. The magnetic dipolar coupling leads
to a splitting in the electron spin resonance frequency of the nitrogen-vacancy
center, allowing readout of the state of a single nitrogen electron spin. At
magnetic fields where the spin splitting of the two centers is the same, we
observe a strong polarization of the nitrogen electron spin. The amount of
polarization can be controlled by the optical excitation power. We combine the
polarization and the readout in time-resolved pump-probe measurements to
determine the spin relaxation time of a single nitrogen electron spin. Finally,
we discuss indications for hyperfine-induced polarization of the nitrogen nuclear
spin.
PMID- 17026337
TI - Isotropic-nematic interface and wetting in suspensions of colloidal platelets.
AB - We study interfacial phenomena in a colloidal dispersion of sterically stabilized
gibbsite platelets, exhibiting coexisting isotropic and nematic phases separated
by a sharp horizontal interface. The nematic phase wets a vertical glass wall and
polarized light micrographs reveal homeotropic surface anchoring both at the free
isotropic-nematic interface and at the wall. On the basis of complete wetting of
the wall by the nematic phase, as found in our density functional calculations
and computer simulations, we analyze the balance between Frank elasticity and
surface anchoring near the contact line. Because of weak surface anchoring, the
director field in the capillary rise region is uniform. From the measured rise (6
microm) of the meniscus at the wall we determine the isotropic-nematic surface
tension to be 3 nN/m, in quantitative agreement with our theoretical and
simulation results.
PMID- 17026338
TI - Nanobubbles in solid-state nanopores.
AB - From conductance and noise studies, we infer that nanometer-sized gaseous bubbles
(nanobubbles) are the dominant noise source in solid-state nanopores. We study
the ionic conductance through solid-state nanopores as they are moved through the
focus of an infrared laser beam. The resulting conductance profiles show strong
variations in both the magnitude of the conductance and in the low-frequency
noise when a single nanopore is measured multiple times. Differences up to 5
orders of magnitude are found in the current power spectral density. In addition,
we measure an unexpected double-peak ionic conductance profile. A simple model of
a cylindrical nanopore that contains a nanobubble explains the measured profile
and accounts for the observed variations in the magnitude of the conductance.
PMID- 17026339
TI - Percolation and epidemic thresholds in clustered networks.
AB - We develop a theoretical approach to percolation in random clustered networks. We
find that, although clustering in scale-free networks can strongly affect some
percolation properties, such as the size and the resilience of the giant
connected component, it cannot restore a finite percolation threshold. In turn,
this implies the absence of an epidemic threshold in this class of networks, thus
extending this result to a wide variety of real scale-free networks which shows a
high level of transitivity. Our findings are in good agreement with numerical
simulations.
PMID- 17026340
TI - Comment on "direct identification of critical clusters in chemical vapor
deposition".
PMID- 17026342
TI - Comment on "experimental observation of the 1/3 magnetization plateau in the
diamond-chain compound Cu3(CO3)2(OH)2".
PMID- 17026344
TI - Can one count the shape of a drum?
AB - Sequences of nodal counts store information on the geometry (metric) of the
domain where the wave equation is considered. To demonstrate this statement, we
consider the eigenfunctions of the Laplace-Beltrami operator on surfaces of
revolution. Arranging the wave functions by increasing values of the eigenvalues,
and counting the number of their nodal domains, we obtain the nodal sequence
whose properties we study. This sequence is expressed as a trace formula, which
consists of a smooth (Weyl-like) part which depends on global geometrical
parameters, and a fluctuating part, which involves the classical periodic orbits
on the torus and their actions (lengths). The geometrical content of the nodal
sequence is thus explicitly revealed.
PMID- 17026345
TI - Bosonic molecules in rotating traps.
AB - We present a variational many-body wave function for repelling bosons in rotating
traps, focusing on rotational frequencies that do not lead to restriction to the
lowest Landau level. This wave function incorporates correlations beyond the
Gross-Pitaevskii (GP) mean-field approximation, and it describes rotating boson
molecules (RBMs) made of localized bosons that form polygonal-ring-like
crystalline patterns in their intrinsic frame of reference. The RBMs exhibit
characteristic periodic dependencies of the ground-state angular momenta on the
number of bosons in the polygonal rings. For small numbers of neutral bosons, the
RBM ground-state energies are found to be always lower than those of the
corresponding GP solutions, in particular, in the regime of GP vortex formation.
PMID- 17026346
TI - Intermediate-temperature superfluidity in an atomic fermi gas with population
imbalance.
AB - We derive the underlying finite temperature theory which describes Fermi gas
superfluidity with population imbalance in a homogeneous system. We compute the
pair formation temperature, superfluid transition temperature Tc, and superfluid
density in a manner consistent with the standard ground state equations and,
thereby, present a complete phase diagram. Finite temperature stabilizes
superfluidity, as manifested by two solutions for Tc or by low T instabilities.
At unitarity, the polarized state is an "intermediate-temperature superfluid."
PMID- 17026347
TI - Methods for scalable optical quantum computation.
AB - We propose a scalable method for implementing linear optics quantum computation
using the "linked-state" approach. Our method avoids the two-dimensional spread
of errors occurring in the preparation of the linked state. Consequently, a proof
is given for the scalability of this modified linked-state model, and an exact
expression for the efficiency of the method is obtained. Moreover, a considerable
improvement in the efficiency, relative to the original linked-state method, is
achieved. The proposed method is applicable to Nielsen's optical "cluster-state"
approach as well.
PMID- 17026348
TI - Globally controlled quantum wires for perfect qubit transport, mirroring, and
computing.
AB - We describe a new design for a q wire with perfect transmission using a uniformly
coupled Ising spin chain subject to global pulses. In addition to allowing for
the perfect transport of single qubits, the design also yields the perfect
"mirroring" of multiply encoded qubits within the wire. We further utilize this
global-pulse generated perfect mirror operation as a "clock cycle" to perform
universal quantum computation on these multiply encoded qubits where the interior
of the q wire serves as the quantum memory while the q-wire ends perform one- and
two-qubit gates.
PMID- 17026349
TI - Toy model of hydrodynamic fluctuations.
AB - We study hydrodynamic fluctuations in an ideal gas. Because one is interested in
thermodynamic properties of small volume elements, Einstein's theory of
equilibrium fluctuations in large systems is insufficient. A toy model of
correlated fluctuations in neighboring small cells leads us to the distinction of
biased and unbiased momentum densities. Hydrodynamic equations that satisfy the
fluctuation-dissipation theorem can then be formulated in terms of these two
different momentum densities or velocities.
PMID- 17026350
TI - Active nematics are intrinsically phase separated.
AB - Two-dimensional nonequilibrium nematic steady states, as found in agitated
granular-rod monolayers or films of orientable amoeboid cells, were predicted
[Europhys. Lett. 62, 196 (2003)10.1209/epl/i2003-00346-7] to have giant number
fluctuations, with the standard deviation proportional to the mean. We show
numerically that the steady state of such systems is macroscopically phase
separated, yet dominated by fluctuations, as in the Das-Barma model [Phys. Rev.
Lett. 85, 1602 (2000)10.1103/PhysRevLett.85.1602]. We suggest experimental tests
of our findings in granular and living-cell systems.
PMID- 17026352
TI - Neutrino signals from the formation of a black hole: A probe of the equation of
state of dense matter.
AB - The gravitational collapse of a nonrotating, black-hole-forming massive star is
studied by nu-radiation-hydrodynamical simulations for two different sets of
realistic equation of state of dense matter. We show that the event will produce
as many neutrinos as the ordinary supernova, but with distinctive characteristics
in luminosities and spectra that will be an unmistakable indication of black hole
formation. More importantly, the neutrino signals are quite sensitive to the
difference of equation of state and can be used as a useful probe into the
properties of dense matter. The event will be unique in that they will be shining
only by neutrinos (and, possibly, gravitational waves) but not by photons, and
hence they should be an important target of neutrino astronomy.
PMID- 17026351
TI - Reconstruction of complex dynamical systems affected by strong measurement noise.
AB - This Letter reports on a new approach to properly analyze time series of
dynamical systems which are spoilt by the simultaneous presence of dynamical
noise and measurement noise. It is shown that even strong external measurement
noise as well as dynamical noise which is an intrinsic part of the dynamical
process can be quantified correctly, solely on the basis of measured time series
and proper data analysis. Finally, real world data sets are presented pointing
out the relevance of the new approach.
PMID- 17026353
TI - Measuring the primordial deuterium abundance during the cosmic dark ages.
AB - We discuss how measurements of fluctuations in the absorption of cosmic microwave
background photons by neutral gas at redshifts z approximately 7-200 could reveal
the primordial deuterium abundance of the Universe. The strength of the cross
correlation of brightness-temperature fluctuations in the redshifted 21-cm line
of hydrogen with those in the redshifted 92-cm line of deuterium is proportional
to the value of the deuterium-to-hydrogen ratio [D/H] fixed during big bang
nucleosynthesis. Although challenging, this measurement would provide the
cleanest possible determination of [D/H], free from contamination by structure
formation processes at lower redshifts. We additionally report our result for the
thermal spin-change cross section in deuterium-hydrogen scattering.
PMID- 17026354
TI - Holographic phase transitions with fundamental matter.
AB - The holographic dual of a finite-temperature gauge theory with a small number of
flavors typically contains D-brane probes in a black hole background. At low
temperature, the branes sit outside the black hole and the meson spectrum is
discrete and possesses a mass gap. As the temperature increases, the branes
approach a critical solution. Eventually, they fall into the horizon and a phase
transition occurs. In the new phase, the meson spectrum is continuous and
gapless. At large Nc and large 't Hooft coupling, we show that this phase
transition is always first order. In confining theories with heavy quarks, it
occurs above the deconfinement transition for the glue.
PMID- 17026355
TI - Low-energy dynamics in ultradegenerate QCD matter.
AB - We study the low-energy behavior of QCD Green functions in the limit that the
baryon chemical potential is much larger than the QCD scale parameter LambdaQCD.
We show that there is a systematic low-energy expansion in powers of
(omega/m)(1/3), where omega is the energy and m is the screening scale. This
expansion is valid even if the effective quark-gluon coupling g is not small. The
expansion is purely perturbative in the magnetic regime |k| >> k0. If the
external momenta and energies satisfy |k| approximately k0, planar, Abelian
ladder diagrams involving the full quark propagator have to be resummed but the
corresponding Dyson-Schwinger equations are closed.
PMID- 17026356
TI - Reduction of the spin-orbit splittings at the n = 28 shell closure.
AB - The N = 28 shell closure has been investigated via the 46Ar(d,p)47Ar transfer
reaction in inverse kinematics. Energies and spectroscopic factors of the neutron
p(3/2), p(1/2), and f(5/2) states in 47Ar were determined and compared to those
of the 49Ca isotone. We deduced a reduction of the N = 28 gap by 330(90) keV and
spin-orbit weakenings of approximately 10(2) and 45(10)% for the f and p states,
respectively. Such large variations for the f and p spin-orbit splittings could
be accounted for by the proton-neutron tensor force and by the density dependence
of the spin-orbit interaction, respectively. This contrasts with the picture of
the spin-orbit interaction as a surface term only.
PMID- 17026357
TI - Enhanced effect of temporal variation of the fine structure constant and the
strong interaction in 229Th.
AB - The relative effects of the variation of the fine structure constant alpha =
e2/variant Planck's over 2pi c and the dimensionless strong interaction parameter
m(q)/LambdaQCD are enhanced by 5-6 orders of magnitude in a very narrow
ultraviolet transition between the ground and the first excited states in the
229Th nucleus. It may be possible to investigate this transition with laser
spectroscopy. Such an experiment would have the potential of improving the
sensitivity to temporal variation of the fundamental constants by many orders of
magnitude.
PMID- 17026358
TI - Symmetry of carrier-envelope phase difference effects in strong-field, few-cycle
ionization of atoms and molecules.
AB - In few-cycle pulses, the exact value of the carrier-envelope phase difference
(CEPD) has a pronounced influence on the ionization dynamics of atoms and
molecules. We show that, for atoms in circularly polarized light, a change in the
CEPD is mapped uniquely to an overall rotation of the system, and results for
arbitrary CEPD are obtained by rotation of the results from a single calculation
with fixed CEPD. For molecules, this is true only for linear molecules aligned
parallel with the propagation direction of the field. The effects of CEPD are
classified as geometric or nongeometric. The observations are exemplified by
strong-field calculations on hydrogen.
PMID- 17026359
TI - Low velocity quantum reflection of Bose-Einstein condensates.
AB - We study how interactions affect the quantum reflection of Bose-Einstein
condensates. A patterned silicon surface with a square array of pillars resulted
in high reflection probabilities. For incident velocities greater than 2.5 mm/s,
our observations agreed with single-particle theory. At velocities below 2.5
mm/s, the measured reflection probability saturated near 60% rather than
increasing towards unity as predicted by the accepted theoretical model. We
extend the theory of quantum reflection to account for the mean-field
interactions of a condensate which suppresses quantum reflection at low velocity.
The reflected condensates show collective excitations as recently predicted.
PMID- 17026360
TI - Unexpected higher-order effects in charged particle impact ionization at high
energies.
AB - Most of the experimental and theoretical studies of electron-impact ionization of
atoms, referred to as (e, 2e), have concentrated on the scattering plane. The
assumption has been that all the important physical effects will be observable in
the scattering plane. However, very recently it has been shown that, for C6+
helium ionization, experiment and theory are in nice agreement in the scattering
plane and in very bad agreement out of the scattering plane. This lack of
agreement between experiment and theory has been explained in terms of higher
order scattering effects between the projectile and target ion. We have examined
electron-impact ionization of magnesium and have observed similar higher-order
effects. The results of the electron-impact ionization of magnesium indicate the
possible deficiencies in the calculation of fully differential cross sections in
previous heavy particle ionization work.
PMID- 17026361
TI - Spontaneous emission of an atom in a cavity with nonorthogonal eigenmodes.
AB - The spontaneous emission of an excited atom in a lossy cavity with nonorthogonal
eigenmodes is analyzed. The quantum Langevin formalism is used to describe the
dynamics of the spontaneous decay. The analysis shows that the spontaneous decay
is modified by the Q value and the effective mode volume factor of each cavity
eigenmode. The effective mode volume is generalized for cavities with
nonorthogonal modes, which can be a very significant modification in the
microcavity regime. It is shown that the spontaneous decay is not enhanced by the
excess noise factor as claimed by other analyses.
PMID- 17026362
TI - Stable control of pulse speed in parametric three-wave solitons.
AB - We analyze the control of the propagation speed of three wave packets interacting
in a medium with quadratic nonlinearity and dispersion. We find analytical
expressions for mutually trapped pulses with a common velocity in the form of a
three-parameter family of solutions of the three-wave resonant interaction. The
stability of these novel parametric solitons is simply related to the value of
their common group velocity.
PMID- 17026363
TI - Mode-coupling control in resonant devices: Application to solid-state ring
lasers.
AB - We report the theoretical and experimental investigation of the effects of mode
coupling in a resonant macroscopic quantum device, in the case of a solid-state
ring laser. This is achieved by introducing an additional coupling source whose
interplay with the already-existing nonlinear effects ensures the coexistence of
two counterpropagating cavity modes yielding a rotation-sensitive beat note. The
determination of the condition for rotation sensing, both theoretically and
experimentally, allows a quantitative study of the role of various mode-coupling
mechanisms, in particular, the gain-induced mode coupling. We point out the
connection between our work and the theoretical work on mode coupling in
superfluid devices. This work opens up the possibility of new types of active
rotation sensors.
PMID- 17026364
TI - Bistable phase locking of a nonlinear optical cavity via rocking: Transmuting
vortices into phase patterns.
AB - We report the experimental observation of the conversion of a phase-invariant
nonlinear system into a bistable phase-locked one via rocking [G. J. de Valcarcel
and K. Staliunas, Phys. Rev. E 67, 026604 (2003)10.1103/PhysRevE.67.026604]. This
conversion results in vortices of the phase-invariant system being replaced by
phase patterns such as domain walls. A model for the experimental device, a
photorefractive oscillator, is given that reproduces the observed behavior.
PMID- 17026365
TI - Scarring by homoclinic and heteroclinic orbits.
AB - In addition to the well-known scarring effect of periodic orbits, we show here
that homoclinic and heteroclinic orbits, which are cornerstones in the theory of
classical chaos, also scar eigenfunctions of classically chaotic systems when
associated closed circuits in phase space are properly quantized, thus
introducing strong quantum correlations. The corresponding quantization rules are
also established. This opens the door for developing computationally tractable
methods to calculate eigenstates of chaotic systems.
PMID- 17026366
TI - Characterizing the dynamical importance of network nodes and links.
AB - The largest eigenvalue of the adjacency matrix of networks is a key quantity
determining several important dynamical processes on complex networks. Based on
this fact, we present a quantitative, objective characterization of the dynamical
importance of network nodes and links in terms of their effect on the largest
eigenvalue. We show how our characterization of the dynamical importance of nodes
can be affected by degree-degree correlations and network community structure. We
discuss how our characterization can be used to optimize techniques for
controlling certain network dynamical processes and apply our results to real
networks.
PMID- 17026367
TI - Thermal rectification in billiardlike systems.
AB - We study the thermal rectification phenomenon in billiard systems with
interacting particles. This interaction induces a local dynamical response of the
billiard to an external thermodynamic gradient. To explain this dynamical effect
we study the steady state of an asymmetric billiard in terms of the particle and
energy reflection coefficients. This allows us to obtain expressions for the
region in parameter space where large thermal rectifications are expected. Our
results are confirmed by extensive numerical simulations.
PMID- 17026368
TI - Instability and evolution of nonlinearly interacting water waves.
AB - We consider the modulational instability of nonlinearly interacting two
dimensional waves in deep water, which are described by a pair of two-dimensional
coupled nonlinear Schrodinger equations. We derive a nonlinear dispersion
relation. The latter is numerically analyzed to obtain the regions and the
associated growth rates of the modulational instability. Furthermore, we follow
the long term evolution of the latter by means of computer simulations of the
governing nonlinear equations and demonstrate the formation of localized coherent
wave envelopes. Our results should be useful for understanding the formation and
nonlinear propagation characteristics of large-amplitude freak waves in deep
water.
PMID- 17026369
TI - Cavitation bubble dynamics inside liquid drops in microgravity.
AB - We studied spark-generated cavitation bubbles inside water drops produced in
microgravity. High-speed visualizations disclosed unique effects of the spherical
and nearly isolated liquid volume. In particular, (1) toroidally collapsing
bubbles generate two liquid jets escaping from the drop, and the "splash jet"
discloses a remarkable broadening. (2) Shock waves induce a strong form of
secondary cavitation due to the particular shock wave confinement. This feature
offers a novel way to estimate integral shock wave energies in isolated volumes.
(3) Bubble lifetimes in drops are shorter than in extended volumes in remarkable
agreement with herein derived corrective terms for the Rayleigh-Plesset equation.
PMID- 17026370
TI - Trapped-particle-mediated collisional damping of nonaxisymmetric plasma waves.
AB - Weak axial variations in magnetic or electric confinement fields in pure electron
plasmas cause slow electrons to be trapped locally, and collisional diffusion
across the trapping separatrix then causes surprisingly large trapped-particle
mediated (TPM) damping and transport effects. Here we characterize TPM damping of
m theta not equal to 0, m(z) = +/-1 Trivelpiece-Gould plasma modes in large
amplitude long-lived Bernstein-Greene-Kruskal states. The TPM damping gives
gammaBGK/omega approximately 10(-4) and seems to dominate in regimes of weak
interparticle collisions.
PMID- 17026371
TI - Observation of instability-induced current redistribution in a spherical-torus
plasma.
AB - A motional Stark effect diagnostic has been utilized to reconstruct the parallel
current density profile in a spherical-torus plasma for the first time. The
measured current profile compares favorably with neoclassical theory when no
large-scale magnetohydrodynamic instabilities are present in the plasma. However,
a current profile anomaly is observed during saturated interchange-type
instability activity. This apparent anomaly can be explained by redistribution of
neutral beam injection current drive and represents the first observation of
interchange-type instabilities causing such redistribution. The associated
current profile modifications contribute to sustaining the central safety factor
above unity for over five resistive diffusion times, and similar processes may
contribute to improved operational scenarios proposed for ITER.
PMID- 17026372
TI - Experimental confirmation of stable, small-debye-length, pure-electron-plasma
equilibria in a stellarator.
AB - The creation of the first small-Debye length, low temperature pure electron
plasmas in a stellarator is reported. A confinement time of 20 ms has been
measured. The long confinement time implies the existence of macroscopically
stable equilibria and that the single particle orbits are well confined despite
the lack of quasisymmetry in the device, the Columbia non-neutral torus. This
confirms the beneficial confinement effects of strong electric fields and the
resulting rapid E x B rotation of the electrons. The particle confinement time is
presently limited by the presence of bulk insulating materials in the plasma,
rather than any intrinsic plasma transport processes. A nearly flat temperature
profile is seen in the inner part of the plasma.
PMID- 17026373
TI - Surface acceleration of fast electrons with relativistic self-focusing in
preformed plasma.
AB - We report an observation of surface acceleration of fast electrons in intense
laser-plasma interactions. When a preformed plasma is presented in front of a
solid target with a higher laser intensity, the emission direction of fast
electrons is changed to the target surface direction from the laser and specular
directions. This feature could be caused by the formation of a strong static
magnetic field along the target surface which traps and holds fast electrons on
the surface. In our experiment, the increase in the laser intensity due to
relativistic self-focusing in plasma plays an important role for the formation.
The strength of the magnetic field is calculated from the bent angle of the
electrons, resulting in tens of percent of laser magnetic field, which agrees
well with a two-dimensional particle-in-cell calculation. The strong surface
current explains the high conversion efficiency on the cone-guided fast ignitor
experiments.
PMID- 17026374
TI - Exotic behavior of hydrogen atoms in solid H2 at temperatures below 1 K.
AB - We present the first magnetic resonance study of atomic hydrogen embedded in
solid H2 films for temperatures 150-900 mK. We found that at T approximately 150
mK average concentrations of H atoms of order 10(18 cm(-3) are very stable
against recombination during two weeks of observations. The distribution of the
population of the two lowest hyperfine states is found to be non-Boltzmann, with
a very large occupation of the ground state. We consider the possibility of
formation in solid H2 of regions with high local concentrations of H atoms, where
collective quantum phenomena might occur.
PMID- 17026375
TI - Bulk-driven nonequilibrium phase transitions in a mesoscopic ring.
AB - We study a periodic one-dimensional exclusion process composed of a driven and a
diffusive part. In a mesoscopic limit where both dynamics compete we identify
bulk-driven phase transitions. We employ mean-field theory complemented by Monte
Carlo simulations to characterize the emerging nonequilibrium steady states.
Monte Carlo simulations reveal interesting correlation effects that we explain
phenomenologically.
PMID- 17026376
TI - Cooperativity beyond caging: Generalized mode-coupling theory.
AB - The validity of mode-coupling theory (MCT) is restricted by an uncontrolled
factorization approximation of density correlations. The factorization can be
delayed and ultimately avoided, however, by explicitly including higher order
correlations. We explore this approach within a microscopically motivated
schematic model. Analytic tractability allows us to discuss in great detail the
impact of factorization at arbitrary order, including the limit of avoided
factorization. Our results indicate a coherent picture for the capabilities as
well as limitations of MCT. Moreover, including higher order correlations
systematically defers the transition and ultimately restores ergodicity. Power
law divergence of the relaxation time is then replaced by continuous but
exponential growth.
PMID- 17026377
TI - Nonlinear dielectric response and thermodynamic heterogeneity in liquids.
AB - If large amplitude time-dependent fields (e.g., dielectric, magnetic, mechanical)
are applied to a sample that displays relaxational modes, some energy of the
external field is absorbed by the slow degrees of freedom. The weak coupling of
these modes to the phonon bath leads to long persistence times of the resulting
higher fictive temperature. Assuming heterogeneities regarding dielectric and
thermal relaxation times, extremely strong nonlinear dielectric effects are
predicted and experimentally verified. For glycerol at T = 213 K, the dielectric
loss measured at 280 kV/cm increases by more than 6% over its low-field value.
This nonlinearity shows a characteristic frequency dependence and implies that
dielectric and thermal time constants are locally correlated in viscous liquids.
PMID- 17026378
TI - How does crystalline substrate plasticity modify thin film buckling?
AB - We report experimental atomic force microscopy observations and analytical
modeling of buckling structures of thin films deposited on single crystal
substrates. The formation of straight-sided blisters just above the step
structures resulting from the dislocations emergence has been observed and
explained in the framework of the Foppl-von Karman theory of thin plates. A
critical step height above which the buckling may occur has been determined and
the asymmetry of the resulting blisters has been explained. Finally, the new
buckling criterion has been compared with the classical one in the plane case and
allows us to explain the blisters localization on step structures.
PMID- 17026379
TI - Continuum theory of nanostructure decay via a microscale condition.
AB - The morphological relaxation of faceted crystal surfaces is studied via a
continuum approach. Our formulation includes (i) an evolution equation for the
surface slope that describes step line tension, g1, and step repulsion energy,
g3; and (ii) a condition at the facet edge (a free boundary) that accounts for
discrete effects via the collapse times, t(n), of top steps. For initial cones
and t(n) approximately t(n)4, we use t(g) from step simulations and predict self
similar slopes in agreement with simulations for any g = g3/g1 > 0. We show that
for g >> 1, (i) the theory simplifies to an equilibrium-thermodynamics model;
(ii) the slope profiles reduce to a universal curve; and (iii) the facet radius
scales as g(-3/4).
PMID- 17026380
TI - Excitonic effects and optical properties of passivated CdSe clusters.
AB - We calculate the optical properties of a series of passivated nonstoichiometric
CdSe clusters using two first-principles approaches: time-dependent density
functional theory within the local-density approximation, and by solving the
Bethe-Salpeter equation for optical excitations with the GW approximation for the
self-energy. We analyze the character of optical excitations leading to the first
low-energy peak in the absorption cross section of these clusters. Within time
dependent density functional theory, we find that the lowest-energy excitation is
mostly a single-level to single-level transition. In contrast, many-body methods
predict a strong mixture of several different transitions, which is a signature
of excitonic effects. The majority of the clusters have a series of dark
transitions before the first bright transition. This may explain the long
radiative lifetimes observed experimentally.
PMID- 17026381
TI - Energy- and momentum-resolved exchange and spin-orbit interaction in cobalt film
by spin-polarized two-electron spectroscopy.
AB - Spontaneous ordering of electronic spins in ferromagnetic materials is one of the
best known and most studied examples of quantum correlations. Exchange
correlations are responsible for long range spin order and the spin-orbit
interaction (SOI) can create preferred crystalline directions for the spins,
i.e., magnetic anisotropy. Presented experimental data illustrate how novel spin
polarized two-electron spectroscopy in-reflection mode allows observation of the
localization of spin-dependent interactions in energy-momentum space. Comparison
of spin-orbit asymmetries in spectra of Co film and clean W(110) may indicate the
presence of interface specific proximity effects providing important clues to the
formation of preferred orientations for the magnetic moment of the Co film. These
results may help to understand the microscopic origin of interface magnetic
anisotropy.
PMID- 17026382
TI - Coulomb blockade and transport in a chain of one-dimensional quantum dots.
AB - A long one-dimensional wire with a finite density of strong random impurities is
modeled as a chain of weakly coupled quantum dots. At low temperature T and
applied voltage V its resistance is limited by breaks: randomly occurring
clusters of quantum dots with a special length distribution pattern that inhibit
the transport. Because of the interplay of interaction and disorder effects the
resistance can exhibit T and V dependences that can be approximated by power
laws. The corresponding two exponents differ greatly from each other and depend
not only on the intrinsic electronic parameters but also on the impurity
distribution statistics.
PMID- 17026383
TI - Controlled flow of spin-entangled electrons via adiabatic quantum pumping.
AB - We propose a method to dynamically generate and control the flow of spin
entangled electrons, each belonging to a spin singlet, by means of adiabatic
quantum pumping. The pumping cycle functions by periodic time variation of
localized two-body interactions. We develop a generalized approach to adiabatic
quantum pumping as traditional methods based on a scattering matrix in one
dimension cannot be applied here. We specifically compute the flow of spin
entangled electrons within a Hubbard-like model of quantum dots, discuss possible
implementations, and identify parameters that can be used to control the singlet
flow.
PMID- 17026384
TI - Zero-field kondo splitting and quantum-critical transition in double quantum
dots.
AB - Double quantum dots offer unique possibilities for the study of many-body
correlations. A system containing one Kondo dot and one effectively
noninteracting dot maps onto a single-impurity Anderson model with a structured
(nonconstant) density of states. Numerical renormalization-group calculations
show that, while band filtering through the resonant dot splits the Kondo
resonance, the singlet ground state is robust. The system can also be
continuously tuned to create a pseudogapped density of states and access a
quantum-critical point separating Kondo and non-Kondo phases.
PMID- 17026385
TI - Optical conductivity of a two-dimensional electron liquid with spin-orbit
interaction.
AB - The interplay of electron-electron interactions and spin-orbit coupling leads to
a new contribution to the homogeneous optical conductivity of the electron
liquid. The latter is known to be insensitive to many-body effects for a
conventional electron system with parabolic dispersion. The parabolic spectrum
has its origin in the Galilean invariance which is broken by spin-orbit coupling.
This opens up a possibility for the optical conductivity to probe electron
electron interactions. We analyze the interplay of interactions and spin-orbit
coupling and obtain optical conductivity beyond RPA.
PMID- 17026386
TI - Generating spin currents in semiconductors with the spin Hall effect.
AB - We investigate electrically induced spin currents generated by the spin Hall
effect in GaAs structures that distinguish edge effects from spin transport.
Using Kerr rotation microscopy to image the spin polarization, we demonstrate
that the observed spin accumulation is due to a transverse bulk electron spin
current, which can drive spin polarization nearly 40 microns into a region in
which there is minimal electric field. Using a model that incorporates the
effects of spin drift, we determine the transverse spin drift velocity from the
magnetic field dependence of the spin polarization.
PMID- 17026387
TI - First-principles calculation of alloy scattering in Ge(x)Si(1-x).
AB - First-principles electronic structure methods are used to find the rates of
intravalley and intervalley n-type carrier scattering due to alloy disorder in
Si(1-x)Ge(x) alloys. The required alloy scattering matrix elements are calculated
from the energy splitting of nearly degenerate Bloch states which arises when one
average host atom is replaced by a Ge or Si atom in supercells containing up to
128 atoms. Scattering parameters for all relevant Delta and L intravalley and
intervalley alloy scattering are calculated. Atomic relaxation is found to have a
substantial effect on the scattering parameters. f-type intervalley scattering
between Delta valleys is found to be comparable to other scattering channels. The
n-type carrier mobility, calculated from the scattering rate using the Boltzmann
transport equation in the relaxation time approximation, is in excellent
agreement with experiments on bulk, unstrained alloys.
PMID- 17026388
TI - Resonantly enhanced nonlinear conductance in long quantum point contacts near
pinch-off.
AB - We report on a remarkable resonance in the differential conductance of long
quantum point contacts (QPCs) that is observed as a precursor to regular
quantized transport. This effect is increasingly pronounced in longer QPCs, in
which the differential conductance may resonantly exceed 2e2/h. From a study of
the experimental characteristics of this feature, we suggest that it may be
associated with the formation of a well-resolved energy gap that opens
dynamically as a result of enhanced many-body interactions in long QPCs.
PMID- 17026389
TI - Phase-charge duality of a josephson junction in a fluctuating electromagnetic
environment.
AB - We have measured the current-voltage characteristics of a single Josephson
junction placed in a high impedance environment. The transfer of Cooper pairs
through the junction is governed by overdamped quasicharge dynamics, leading to
Coulomb blockade and Bloch oscillations. Exact duality exists to the standard
overdamped phase dynamics of a Josephson junction, resulting in a dual shape of
the current-voltage characteristic, with current and voltage changing roles. We
demonstrate this duality with experiments which allow for a quantitative
comparison with a theory that includes the effect of fluctuations due to the
finite temperature of the electromagnetic environment.
PMID- 17026390
TI - Variable orbital coupling in a two-dimensional quantum-dot solid probed on a
local scale.
AB - The optoelectronic properties of semiconductor quantum-dot (QD) solids depend on
the electronic structure of the building blocks and their interactions. Disorder
may affect the coupling on a local scale. We have measured the density of states
of 2D arrays of PbSe QDs site by site using scanning tunneling spectroscopy. It
markedly differs from that of isolated QDs due to electronic coupling in the
array. We observe strong local variations in the coupling strength with two
prototypical cases: delocalization of the conduction electrons only, and full
coupling with both hole and electron delocalization over the QD sites in the
array.
PMID- 17026392
TI - Spin excitations in fluctuating stripe phases of doped cuprate superconductors.
AB - Using a phenomenological lattice model of coupled spin and charge modes, we
determine the spin susceptibility in the presence of fluctuating stripe charge
order. We assume the charge fluctuations to be slow compared to those of the
spins, and combine Monte Carlo simulations for the charge order parameter with
exact diagonalization of the spin sector. Our calculations unify the spin
dynamics of both static and fluctuating stripe phases and support the notion of a
universal spin excitation spectrum in doped cuprate superconductors.
PMID- 17026391
TI - Electron-magnon coupling and nonlinear tunneling transport in magnetic
nanoparticles.
AB - We present a theory of single-electron tunneling transport through a
ferromagnetic nanoparticle in which particle-hole excitations are coupled to spin
collective modes. The model employed to describe the interaction between
quasiparticles and collective excitations captures the salient features of a
recent microscopic study. Our analysis of nonlinear quantum transport in the
regime of weak coupling to the external electrodes is based on a rate-equation
formalism for the nonequilibrium occupation probability of the nanoparticle many
body states. For strong electron-boson coupling, we find that the tunneling
conductance as a function of bias voltage is characterized by a large and dense
set of resonances. Their magnetic field dependence in the large-field regime is
linear, with slopes of the same sign. Both features are in agreement with recent
tunneling experiments.
PMID- 17026393
TI - Low-energy electrodynamics of superconducting diamond.
AB - Heavily boron-doped, diamond films can become superconducting with critical
temperatures Tc well above 4 K. Here we first measure the reflectivity of such a
film down to 5 cm(-1), by also using coherent synchrotron radiation. We thus
determine the optical gap 2Delta, the field penetration depth lambda, the range
of action of the Ferrell-Glover-Tinkham sum rule, and the electron-phonon
spectral function alpha2F(omega). We conclude that diamond behaves as a dirty BCS
superconductor.
PMID- 17026394
TI - Organometallic benzene-vanadium wire: A one-dimensional half-metallic
ferromagnet.
AB - Using density functional theory we perform theoretical investigations of the
electronic properties of a freestanding one-dimensional organometallic vanadium
benzene wire. This system represents the limiting case of multidecker
Vn(C6H6)(n+1) clusters which can be synthesized with established methods. We
predict that the ground state of the wire is a 100% spin-polarized ferromagnet
(half-metal). Its density of states is metallic at the Fermi energy for the
minority electrons and shows a semiconductor gap for the majority electrons. We
find that the half-metallic behavior is conserved up to 12% longitudinal
elongation of the wire. Ab initio electron transport calculations reveal that
finite size vanadium-benzene clusters coupled to ferromagnetic Ni or Co
electrodes will work as nearly perfect spin filters.
PMID- 17026395
TI - Interface coupling transition in a thin epitaxial antiferromagnetic film
interacting with a ferromagnetic substrate.
AB - We report experimental evidence for a transition in the interface coupling
between an antiferromagnetic film and a ferromagnetic substrate. The transition
is observed in a thin epitaxial NiO film grown on top of Fe(001) as the film
thickness is increased. Photoemission electron microscopy excited with linearly
polarized x rays shows that the NiO film is antiferromagnetic at room temperature
with in-plane uniaxial magnetic anisotropy. The anisotropy axis is perpendicular
to the Fe substrate magnetization when the NiO thickness is less than about 15 A,
but rapidly becomes parallel to the Fe magnetization for a NiO coverage higher
than 25 A.
PMID- 17026396
TI - Ferroelectric polarization flop in a frustrated magnet MnWO4 induced by a
magnetic field.
AB - The relationship between magnetic order and ferroelectric properties has been
investigated for MnWO4 with a long-wavelength magnetic structure. Spontaneous
electric polarization is observed in an elliptical spiral spin phase. The
magnetic-field dependence of electric polarization indicates that the
noncollinear spin configuration plays a key role for the appearance of the
ferroelectric phase. An electric polarization flop from the b direction to the a
direction has been observed when a magnetic field above 10 T is applied along the
b axis. This result demonstrates that an electric polarization flop can be
induced by a magnetic field in a simple system without rare-earth 4f moments.
PMID- 17026397
TI - Lattice disorder and size-induced kondo behavior in CeAl2 and CePt(2+x).
AB - When the size of CeAl2 and CePt(2+x) particles is reduced to the nanometer scale,
antiferromagnetism is suppressed and Kondo behavior predominates, with the Kondo
temperature T(K) either decreasing (CeAl2) or increasing (CePt(2+x)) relative to
the bulk. Local structure measurements show that these nanoparticles are
significantly distorted. While such distortions should strongly affect magnetic
and electronic properties, we find they cannot explain the observed changes in
T(K). Other size-induced changes to the electronic structure must, therefore,
play a significant role.
PMID- 17026398
TI - Spin transfer in magnetic tunnel junctions with hot electrons.
AB - Recent data on the bias dependence of the spin transfer effect in magnetic tunnel
junctions have shown that torque remains intact at bias voltages for which the
tunneling magnetoresistance has been strongly reduced. We show that the current
induced excitations due to hot electrons, while reducing the magnetoresistance,
enhance both the charge current and the spin transfer in magnetic tunnel
junctions in such a manner that the ratio of the torque to the charge current
does not significantly change.
PMID- 17026399
TI - Long-range spin-qubit interaction mediated by microcavity polaritons.
AB - We study the optically induced coupling between spins mediated by polaritons in a
planar microcavity. In the strong-coupling regime, the vacuum Rabi splitting
introduces anisotropies in the spin coupling. Moreover, due to their photonlike
mass, polaritons provide an extremely long spin coupling range. This suggests the
realization of two-qubit all-optical quantum operations within tens of
picoseconds with spins localized as far as hundreds of nanometers apart.
PMID- 17026400
TI - Dominant effect of polariton-polariton interactions on the coherence of the
microcavity optical parametric oscillator.
AB - The importance of interaction effects in determining the temporal coherence of
spectrally and spatially isolated single modes of the microcavity optical
parametric oscillator (OPO) is demonstrated. As a function of macroscopic
occupancy, the coherence time (tau c) first increases linearly and then exhibits
saturation behavior, reaching maximum values of up to 500 ps. Good agreement is
found with a model including fluctuations in polariton number and polariton
polariton interactions between the OPO states. tau c is a property of the coupled
OPO system, a result confirmed by the finding of equal coherence times for signal
and idler, even though the idler is subject to strong additional scattering.
PMID- 17026401
TI - Attraction between like-charged walls: Short-ranged simulations using local
molecular field theory.
AB - Effective attraction between like-charged walls mediated by counterions is
studied using local molecular field (LMF) theory. Monte Carlo simulations of the
"mimic system" given by LMF theory, with short-ranged "Coulomb core" interactions
in an effective single particle potential incorporating a mean-field average of
the long-ranged Coulomb interactions, provide a direct test of the theory, and
are in excellent agreement with more complex simulations of the full Coulomb
system by Moreira and Netz [Eur. Phys. J. E 8, 33 (2002)]. A simple, generally
applicable criterion to determine the consistency parameter sigma(min) needed for
accurate use of the LMF theory is presented.
PMID- 17026402
TI - Vortex flow in freestanding smectic films driven by elastic relaxation of the c
director.
AB - We report a simple experiment in freestanding smectic films in which elastic
distortions of the c director drive macroscopic flow. The flow field is
visualized with tracer particles. Measurements are compared to predictions of a
model that employs the coupled dynamic equations for director and velocity
fields. Relaxation dynamics depends on the topology of the film center: for
defect-free target patterns, shear flow provides the dominating contribution to
the c director dynamics. In presence of a central topological defect of strength
S = + 1, the influence of flow on the relaxation dynamics is practically
negligible, while for a central S = - 1 defect, the influence of vortex flow on
the c-director relaxation is roughly twice as large as for the defect-free state.
PMID- 17026403
TI - Superlattice formation in a binary mixture of block copolymer micelles.
AB - A binary solution mixture of distinct block copolymer micelles is found to adopt
a superlattice. The larger micelles, formed from polystyrene-polyisoprene
diblocks, have a nominal radius of 29 nm; the smaller micelles, formed from
polystyrene-polydimethylsiloxane diblocks, have a nominal radius of 16 nm. The
superlattice unit cell dimension is 156 nm and is assigned to space group Fm3c;
it corresponds to the AB13 structure. As these diblocks are uncharged, the
driving force for superlattice formation is primarily free volume entropy, as in
sterically stabilized colloidal hard spheres.
PMID- 17026405
TI - Fisher information for spike-based population decoding.
AB - We evaluate the Fisher information of a population of model neurons that receive
dynamical input and interact via spikes. With spatially independent threshold
noise, the spike-based Fisher information that summarizes the information carried
by individual spike timings has a particularly simple analytical form. We
calculate the loss of information caused by abandoning spike timing and study the
effect of synaptic connections on the Fisher information. For a simple
spatiotemporal input, we derive the optimal recurrent connectivity that has a
local excitation and global inhibition structure. The optimal synaptic
connections depend on the spatial or temporal feature of the input that the
system is designed to code.
PMID- 17026404
TI - Stall, spiculate, or run away: The fate of fibers growing towards fluctuating
membranes.
AB - We study the dynamics of a growing semiflexible fiber approaching a membrane at
an angle. At late times we find three regimes: fiber stalling, when growth stops,
runaway, in which the fiber bends away from the membrane, and another regime in
which spicules form. We discuss which regions of the resulting "phase diagram"
are explored by (i) single and bundled actin fibers in living cells, (ii) sickle
hemoglobin fibers, and (iii) microtubules inside vesicles. We complement our
analysis with 3D stochastic simulations.
PMID- 17026406
TI - Negative tension induced by lipid uptake.
AB - Membrane fusion is an important process in cell biology. While the molecular
mechanisms of fusion are actively studied at a very local scale, the consequences
of fusion at a larger scale on the shape and stability of the membrane are still
not explored. In this Letter, the evolution of the membrane tension during the
fusion of positive small unilamellar vesicles with a negative giant unilamellar
vesicle has been experimentally investigated and compared to an existing
theoretical model. The tension has been deduced using videomicroscopy from the
measurement of the fluctuation spectrum and of the time correlation function of
the fluctuations. We show that fusion induces a strong decrease in the effective
tension of the membrane which eventually reaches negative values. Under these
conditions, we show that localized instabilities appear on the vesicle. The
membrane finally collapses, forming dense lipid structures.
PMID- 17026407
TI - Nanophase-separated synchronizing structure with parallel double periodicity from
an undecablock terpolymer.
AB - A new nanophase-separated structure with parallel double periodicity has been
identified for an undecablock terpolymer in bulk. The polymer includes two long
poly(2-vinypyridine) (P) chains on each end, with five short polyisoprene (I) and
four short polystyrene (S) chains at the center. This polymer exhibits a
hierarchical lamellar structure with two crystallographic periods: 88 nm and 16
nm. The 88 nm period includes one thick P lamella and five thin I-S-I-S-I
lamellae, of extremely high orientation.
PMID- 17026408
TI - Additive decomposition of shear strength in cohesive granular media from grain
scale interactions.
AB - We study cemented granular media by introducing cohesive bonding (sliding or
rolling friction and tensile strength) between grains in the framework of the
contact dynamics method. We find that, for a wide range of bond parameters, the
macroscopic angle of friction at the peak state can be split into three distinct
terms of collisional, frictional and dilational origins. Remarkably, the
macroscopic tensile strength depends only on the bond tensile strength, and the
friction angle at the peak state is proportional to the dilatancy angle which
varies linearly with sliding friction.
PMID- 17026409
TI - Screening and fundamental length scales in semidilute Na-DNA aqueous solutions.
AB - The fundamental length scales in semidilute Na-DNA aqueous solutions have been
investigated by dielectric spectroscopy. The low- and the high-frequency
relaxation modes are studied in detail. The length scale of the high-frequency
relaxation mode at high DNA concentrations can be identified with the de Gennes
Pfeuty-Dobrynin correlation length of polyelectrolytes in semidilute solution,
whereas at low DNA concentrations and in the low added salt limit the length
scale shows an unusual exponent reminiscent of semidilute polyelectrolyte chains
with hydrophobic backbone. The length scale of the low-frequency relaxation mode
corresponds to a Gaussian chain composed of correlation blobs in the low added
salt limit, and to the Odijk-Skolnick-Fixman value of the single chain
persistence length in the high added salt limit.
PMID- 17026410
TI - Measuring the force of interaction between a metallic probe and a single
molecule.
AB - Precision current measurements are recorded at 5 K during the approach and
contact between a Pt-inked probe and the carbon-carbon double-bond region of an
isolated 1,3-cyclohexadiene molecule chemisorbed on a Si(100) surface. Scanning
tunneling spectroscopic data reveal systematic features in the current at
specific probe-molecule separations. Aided by density functional theory
calculations, we show that these features arise from interaction forces between
the probe and molecule, which can be interpreted as the relaxation of the probe
molecule system prior to and during contact.
PMID- 17026411
TI - Increasing primary care physician productivity: A case study.
AB - OBJECTIVE: To ascertain the impact of advanced access and productivity-based pay
on physician productivity and compensation, patient satisfaction, and medical
group cost of delivering care. STUDY DESIGN: Longitudinal case study. METHODS:
Study subjects were 105 primary care physicians (PCPs) continuously employed at a
Minnesota medical group that implemented major changes in access to primary care
appointments and to PCP compensation arrangements in 2000. We tracked physician
productivity, physician compensation, patient satisfaction, and cost to the
medical group per relative value unit (RVU) of patient care from 1998 through
2002. RESULTS: In 1998, 105 PCPs (99.6 full-time equivalents [FTEs]) generated
275,000 work RVUs (WRVUs), and PCP pay averaged 123,500 dollars per FTE. In 2002,
the same 105 PCPs (now 98.1 FTEs) generated 374,000 WRVUs and 148,000 dollars pay
per FTE. From 1998 through 2002, WRVUs per FTE rose 38%, PCP compensation
increased 20%, cost of PCP compensation per WRVU produced fell by 13%, overall
direct cost of running the clinics per total RVU fell by 20%, and patient
satisfaction remained constant. Improvement in operating costs was due to
increased physician productivity, lower physician compensation per RVU, and a
decline in support staff per 10,000 RVUs from 6.80 to 4.50. CONCLUSIONS: It is
possible to substantially and simultaneously improve costs of care, physician
compensation, and patient access without harming patient satisfaction. Advanced
access and productivity-based pay may be effective ways to address the challenges
of timeliness, efficiency, and patient centeredness identified by the Institute
of Medicine.
PMID- 17026412
TI - Outpatient medication use and health outcomes in post-acute coronary syndrome
patients.
AB - OBJECTIVE: To investigate the pattern of postdischarge evidence-based outpatient
medication use and its impact on subsequent hospital readmissions in post-acute
coronary syndrome (ACS) patients. STUDY DESIGN: Prospective observational study.
METHODS: A telephone survey was conducted to collect information from discharge
to 8 months after discharge for 433 patients hospitalized with a primary
diagnosis of ACS in 5 mid-Michigan hospitals. The survey data were then merged
with chart review data from the initial hospitalization. We first conducted a
longitudinal descriptive analysis of the utilization patterns of patient self
reported medication use from discharge to the 8-month survey. Then, multivariable
logit analysis was used to estimate the effect of post-ACS medication use on self
reported hospital readmission at 3 months and 8 months after discharge.
Propensity score matching was used to counter the possible bias induced by self
selection of outpatient medication use. RESULTS: The pattern of outpatient
medication use was dynamic. Most changes to medication regimens occurred within 3
months after discharge, with fewer changes in the subsequent 5 months. Taking a
beta-blocker, angiotensin-converting enzyme inhibitor, or angiotension receptor
blocker significantly reduced the probability of hospital readmission 3 months
after discharge. Propensity score matching produced similar statistically
significant results. Re-hospitalization within 3 months after discharge was a
strong predictor of later hospital readmission up to 8 months. CONCLUSION: Timely
and appropriate medication adjustment in outpatient settings appears to be
critically important to reduce hospital readmission among ACS patients.
PMID- 17026413
TI - Low-density lipoprotein cholesterol goal attainment among high-risk patients:
Does a combined intervention targeting patients and providers work?
AB - BACKGROUND: Physicians are aware of the National Cholesterol Education Program
guidelines; however, most patients fail to attain cholesterol goals. OBJECTIVE:
To determine whether a combined program of patient education and provider
awareness could improve the National Cholesterol Education Program goal
attainment among patients at high risk for cardiovascular events. METHODS: One
hundred seven high-risk patients with cardiovascular disease were educated in a
single 15-minute session regarding their cholesterol levels, risk factors, and
medication adherence. Those with scores of 2 or lower on the Morisky
questionnaire were classified as low-adherence patients, and those with scores of
3 or higher were classified as high-adherence patients. Seven physicians were
provided this information and were requested to evaluate the dyslipidemia
management of these patients. Lipid levels were reevaluated 8 to 12 weeks after
the intervention. RESULTS: At the start of the study, 38 (35.5%) of the 107
patients were at target low-density lipoprotein cholesterol (LDL-C) levels, and
64 of the 107 patients (59.8%) were at target levels after the intervention. High
adherence patients decreased their LDL-C levels from a mean of 118.6 mg/dL (3.07
mmol/L) to 98.6 mg/dL (2.55 mmol/L); low-adherence patients increased their LDL-C
levels after the intervention from 134.5 mg/dL (3.48 mmol/L) to 142.1 mg/dL (3.68
mmol/L). A comparison between the LDL-C goal achievers vs nonachievers revealed a
significant difference in adherence (P = .001). Among the goal achievers,
significant decreases in preintervention vs postintervention total cholesterol
levels (P = .001) and LDL-C levels (P = .001) were also noted. CONCLUSION: This
study demonstrates that an intervention simultaneously targeting patients and
providers is successful in improving goal attainment among high-risk patients.
PMID- 17026414
TI - Implementation of evidence-based alcohol screening in the Veterans Health
Administration.
AB - BACKGROUND: Despite evidence-based guidelines, brief alcohol screening and
counseling have not been routinely integrated into most primary care practices in
the United States. OBJECTIVE: To describe the results of the implementation of
evidence-based alcohol screening by the Veterans Health Administration (VA) in
2004, as the first step toward implementation of brief alcohol counseling. STUDY
DESIGN: This observational study of outpatients from all 21 VA networks relied on
the following 2 data sources from the VA Office of Quality and Performance: (1)
Medical record reviews, designed to compare VA networks quarterly, evaluated
whether established VA patients had documented screening for alcohol misuse and
documented follow-up assessment for alcohol use disorders among those who
screened positive for alcohol misuse (January-March 2005); and (2) Mailed patient
satisfaction surveys from 2004, which oversampled patients new to the VA
(response rate, >70%), included the Alcohol Use Disorders Identification Test
Consumption (AUDIT-C) questions and asked about past-year advice "to drink less
or not to drink alcohol" from a VA provider. RESULTS: Based on 10 115 medical
record reviews, 93% (range, 89%-96% across networks) of outpatients were screened
for alcohol misuse, and 25% (range, 11%-36%) screened positive. Among screen
positive patients, 42% (range, 5%-84%) had documented follow-up assessment, but
absolute numbers of screen-positive patients evaluated were small (27-80 patients
per network). Based on 235 481 patient surveys, the prevalence of alcohol misuse
was 22% (range, 15%-27% across networks), and 28% (range, 20%- 36%) of screen
positive patients reported receiving alcohol-related advice. Alcohol-related
advice increased as AUDIT-C scores increased. CONCLUSION: The VA successfully
implemented evidence-based alcohol screening, but the rate of follow-up among
screen-positive patients remained low.
PMID- 17026416
TI - A step therapy algorithm for the treatment and management of chronic depression.
AB - Depression is a chronic and progressive condition that, when not treated
adequately, can lead to severe morbidity and mortality in patients and increased
costs for health plans. Despite the significance of this disease state, the
majority of patients are not treated adequately to the widely accepted goal of
remission. Patients who do not achieve remission are at greater risk of relapse
and recurrence, more chronic depressive episodes, and a shorter duration between
depressive episodes. Modeled partially after the Sequenced Treatment Algorithm to
Relieve Depression (STAR*D) trial and based on trial data and the consensus
statements of a panel of clinical professionals, a step therapy algorithm is
proposed in this supplement, including considerations for screening and
intervention. The primary concepts in the development of this algorithm were the
use of the same clinical tool for both screening and diagnosis and the
incorporation of frequent follow-up visits or calls to continuously monitor
progress in patients being treated. Also discussed are considerations for drug
therapy choices when switching is deemed necessary. Switching to a drug from a
different class of agents than the failed trial drug is recommended based on the
differential mechanism of action between classes.
PMID- 17026415
TI - Association of income and prescription drug coverage with generic medication use
among older adults with hypertension.
AB - OBJECTIVE: To determine whether low-income seniors and those without prescription
drug coverage are more likely to use generic cardiovascular drugs than more
affluent and better insured adults. STUDY DESIGN: Cross-sectional analysis.
METHODS: We used data from the 2001 Medicare Current Beneficiary Survey. Analyses
included noninstitutionalized survey respondents over age 65 years with
hypertension who used > or =1 multisource cardiovascular drugs (N = 1710). We
examined the association of income and prescription coverage with use of generic
versions of multisource drugs from 5 classes: angiotensin-converting enzyme (ACE)
inhibitors, beta-adrenergic receptor antagonists (beta-blockers), calcium channel
blockers, alpha1-adrenergic receptor antagonists (alpha-blockers), and thiazide
diuretics. RESULTS: Rates of generic medication use were 88.5% (beta-blockers);
92.8% (thiazides); 58.7% (calcium channel blockers); 60.7% (ACE inhibitors); and
52.6% (alpha-blockers). In multivariate analysis of generic medication use
aggregated across the 5 drug classes, individuals with incomes below 200% of the
federal poverty level were modestly more likely to use generic medications
compared with seniors with incomes above 300% of the poverty level. Seniors who
lacked prescription coverage were more likely to use generics than those who had
employer-sponsored coverage, although the association was of marginal statistical
significance (relative risk = 1.29, 95% confidence interval = 1.00, 1.60).
CONCLUSION: Seniors with low incomes or no prescription coverage were only
somewhat more likely to use generic cardiovascular drugs than more affluent and
insured seniors. These findings suggest that physicians and policy makers may be
missing opportunities to reduce costs for Medicare and its economically
disadvantaged beneficiaries.
PMID- 17026420
TI - The practice and politics of Indigenous health nursing.
PMID- 17026421
TI - Indigenous health care: advances in nursing practice.
PMID- 17026422
TI - Critical cultural perspectives and health care involving Aboriginal peoples.
AB - Despite a growing body of critical scholarship in nursing, the concept of culture
continues to be applied in ways that diminish the significance of power relations
and structural constraints on health and health care. In this paper, we take a
critical look at how assumptions and ideas underpinning conceptualizations of
culture and cultural sensitivity can influence nurses' perceptions of Aboriginal
peoples and Aboriginal health. Drawing on examples from our research, we examine
how popularized assumptions about culture can shape nurses' views of Aboriginal
patients. These assumptions and perceptions require closer scrutiny because of
their potential to influence nurses' practice with Aboriginal patients. Our
specific aims are to: (a) consider some of the limitations of cultural
sensitivity in relation to health care involving Aboriginal peoples; (b) explore
how ideas about culture have the potential to become problematic in nursing
practice with Aboriginal peoples; and (c) explore the relevance of a 'critical
cultural approach' in extending our understanding of culture in relation to
Aboriginal peoples' health. We discuss a critical cultural perspective as one way
of broadening nurses' understandings about the complexities of culture and the
many facets of culture that require critical consideration. In relation to
Aboriginal health, this will require nurses to develop greater critical awareness
of culture as a relational process, and as necessarily influenced by issues of
racism, colonialism, historical circumstances, and the current political climate
in which we live.
PMID- 17026423
TI - Issues of language across the cultural [and colonial] divide.
PMID- 17026424
TI - It's only a mistake if you make it twice.
PMID- 17026425
TI - Decolonisation: a critical step for improving Aboriginal health.
AB - Aboriginal health continues to be in crisis in Australia although expenditure has
increased in service provision, strategic planning, research and policy
development over the last thirty years. This paper recommends that a shift must
occur to make Aboriginal health improvement a reality. This shift requires the
decolonising of Aboriginal health so that the experts in Aboriginal health,
namely Aboriginal people, can voice and action initiatives that address their
health issues. This shift is from the current western dominant approach that
continues to manage Aboriginal health in its linear spectrum of illness and
disease. Aboriginal people view health differently; their contexts for health
issues are also diverse requiring a more holistic and informed response.
PMID- 17026426
TI - Amorphous practice: nursing in a remote Indigenous community of Australia.
AB - Nurses are key providers of health care in remote Indigenous communities
throughout Australia. Evidence of nurses' actual practice and the outcomes of
their care for clients in this context, however, is lacking. This exploratory
research describes how nursing is practised in a remote Aboriginal community and
reveals many anomalies. The overall theme, termed amorphous practice, defines the
changeable character of practice from nurse to nurse and from situation to
situation. The themes underlying amorphous practice are termed detachment,
diffusion, and beyond the nursing domain. Each theme is described by way of its
characteristics, the strategies nurses use to deal with the situation, and the
consequences. The significance of these findings raise concerns for the
accountability of nursing and most of all for the rights of Indigenous people in
remote areas to basic standards of safe health care.
PMID- 17026427
TI - Characterising Maori nursing practice.
AB - This paper summarises research which addresses the question What might constitute
Maori nursing practice? The research design adopted was influenced by Kaupapa
Maori methodology and used a semi-structured, qualitative, in-depth interview
process. It was found that by understanding the current experiences of Maori
registered nurses, their reflections on their preparation for practice, and their
current practice, we are able to identify the present and future training and
practice needs of Maori nurses. Maori nursing practice can be characterised as
having five features: the promotion of cultural affirmation including cultural
awareness and identity; the support of, and access to Maori networks; the
adoption of Maori models of health; the enabling of visibility and pro-activity
as Maori nurses; and, the validation of Maori nurses as effective health
professionals. Three recommendations for promoting Maori nursing practice are
made in relation to staff in the workplace and in nurse education programmes. All
nursing staff need to be alert to: 1. The impact of western scientific models on
Maori healthcare; 2. The (often passive) non-acceptance of Maori within
mainstream institutions; and 3. The benefits of valuing Indigenous nursing
programmes.
PMID- 17026428
TI - Indigenous values, cultural safety and improving health care: the case of Native
Hawaiians.
PMID- 17026429
TI - Assessing pain across the cultural gap: Central Australian Indigenous peoples'
pain assessment.
AB - Pain is a dynamic, unpleasant sensory experience with many physical,
psychological, and social implications. Assessment of pain within a bicultural
environment has the potential to cause ineffective pain management and
unnecessary suffering amongst Indigenous people. It has been recognised that non
Indigenous nurses sometimes demonstrate culturally unsafe practices during the
pain assessment process. These practices have arisen due to limited knowledge of
what constitutes 'cultural safety' and how nurses can apply this concept during
pain assessment. Culturally safe pain assessment strategies have been developed
based upon research findings and through consultation with Indigenous people.
PMID- 17026430
TI - At what cost to health? Tlicho women's medical travel for childbirth.
AB - Medical travel policies are instituted in all rural and remote areas of Canada as
a means of providing universal health care services to residents. These policies
are framed, developed and implemented from a colonial perspective and require re
examination through a more inclusive and collaborative postcolonial lens. The
purpose of this paper is to discuss the medical travel policy for childbirth in
Canada's Northwest Territories from a postcolonial perspective and in
consideration of the cultural safety of pregnant Tlicho women. The context within
which Tlicho birthing and this policy thrives is reviewed along with the
exploration of future possibilities. Personal, socioeconomic, political and legal
factors surrounding birthing are highlighted. It is anticipated, that by
illuminating the oppressive and paternalistic nature of this childbirth policy,
there will be heightened awareness that fosters transitions within the system to
transform current risk discourse creating new possibilities for Tlicho women in
the birth of their babies.
PMID- 17026431
TI - Insights on Aboriginal peoples' views of cancer in Australia.
AB - Although the incidence of cancer in Indigenous peoples is similar to its
incidence in the overall Australian population, Indigenous peoples are less
likely to access early detection and medical interventions resulting in higher
mortality and morbidity rates. To explore and address this discrepancy, the
National Health and Medical Research Council funded a research study to examine
Indigenous peoples' views of cancer and cancer treatments with an end goal of
developing an innovative model of Indigenous Palliative Care. Seventy-two
participants were interviewed from four geographical areas within the Northern
Territory (Australia) including patients, caregivers, Indigenous and non
Indigenous health care workers, and interpreters. Indigenous peoples' views of
cancer have to be examined within a historical, socio-political, and cultural
context. There is no Indigenous word for cancer and the Western biomedical
language that semantically constructs the notion of cancer is not widely
understood. Additionally, for many Indigenous people, the aetiology of cancer is
embedded in beliefs about the spiritual world of curses and payback from
perceived misdeeds. The paper advocates for cross-cultural education initiatives,
stressing the importance of a two way education strategy incorporating a process
whereby medical and nursing personnel would improve their understanding of
Indigenous peoples' view of cancer and Indigenous peoples would learn more about
prevention and treatment of cancer from a biomedical perspective.
PMID- 17026432
TI - The experience of whanau caring for members disabled from the effects of a
cerebro-vascular accident.
AB - The study sought to understand the experience of Maori in accepting
responsibility for the care of a whanau member following a cerebro-vascular
accident (CVA). The importance and role of whanau, kaumatua and kuia to Maori as
a distinctive ethnic entity is well known and acknowledged in coming to an
understanding of Maori society. Whanau has a very large part to play in the care
of the family member disabled by CVA. There is extensive literature that deals
with these issues, yet there is little that deals with disability issues and in
particular those issues that arise following CVA. A qualitative study was
conducted examining the experience of Whanau caring for members disabled from the
effects of CVA. Individual and focus group interviews were undertaken with Maori
patients and their caregivers to explore this phenomenon. Data were analysed
using a thematic analysis approach and highlighted three time stages of concern,
namely (1) the onset of the event, (2) hospitalisation, and (3) discharge care.
PMID- 17026433
TI - Nursing partnerships in Indigenous health.
PMID- 17026434
TI - Relationship building for research: the Southern Saskatchewan/Urban Aboriginal
Health Coalition.
AB - The Southern Saskatchewan/Urban Aboriginal Health Coalition is an
interdisciplinary, intersectoral team of researchers and communities dedicated to
exploring what 'culturally respectful' care means in Aboriginal communities.
Although the purpose of the research project was to examine this concept in an
effort to improve health care service delivery and education for health
professions, the members of the Coalition realized early in the process that one
of the primary factors related to the success of the project would be the
building and sustaining of relationships. This paper describes a relational
process that was used to initiate, facilitate, and support a research partnership
with the Aboriginal communities. Through a community-based process, two
communities and the Coalition used sharing circles and workshops as a method to
create relationships and begin a discussion about what constitutes key elements
of culturally respectful health care and education. These elements have not yet
been determined as the Coalition and community members have focused on fostering
relationships which have been critical to building the partnership with the
Aboriginal communities.
PMID- 17026435
TI - A nursing partnership for better outcomes in Aboriginal mental health, including
substance use.
AB - This article draws on our participatory action research findings and
interventions, such as advocacy and professional education, as applied during and
after a large project focusing on Aboriginal mental health and safe medication
management. The project was conducted by our research team and partners,
community-controlled Aboriginal health services, and community leaders. The paper
provides a discussion of major Aboriginal mental health issues gleaned from the
literature, along with a discussion, and a conceptual model for conducting
ethical Aboriginal health research, that has both evolved and guided us. It is
hoped that this paper will assist nurses and other professional colleagues to
work more effectively with Aboriginal peoples.
PMID- 17026436
TI - Meeting the health needs of Indigenous people: how is nursing education meeting
the challenge?
AB - Australian Indigenous people continue to have health outcomes that are near to
the worst in the world but similar to those of the Indigenous peoples in
countries such as Canada and New Zealand. Numerous policies and strategies have
been implemented in Australia in an attempt to rectify this situation. This paper
provides an overview of the issues directly related to the provision of a skilled
workforce prepared for delivery of appropriate health services to Indigenous
people. It includes an overview of the need for Indigenous people in nursing and
the issues facing them when they enrol in undergraduate nursing courses. It also
proposes changes necessary to ensure non-indigenous nurses are better prepared to
work effectively with Indigenous people in the future.
PMID- 17026437
TI - The Yapunyah project: embedding Aboriginal and Torres Strait Islander
perspectives in the nursing curriculum.
AB - The Yapunyah Project is an initiative of the Faculty of Health at Queensland
University of Technology. It was instigated to further improve the development of
cultural competence in health graduates with respect to Aboriginal and Torres
Strait Islander perspectives. The project was informed by the cultural competence
in healthcare delivery models of Campinha-Bacote (1998a) and Cross, Bazron,
Dennis and Isaacs (1989) and by the cultural safety reforms to nursing curricula
in New Zealand. The Yapunyah Project involved extensive consultation and
collaboration with Indigenous staff and health experts in the local Aboriginal
and Torres Strait Islander community. A core curriculum, and associated graduate
transcultural competencies, were informed by these discussions and earlier
reforms in health curricula by the Committee of Deans of Australian Medical
Schools and the Royal Australian College of General Practitioners. Although the
overall project involved four separate schools within the faculty, this paper
details the experience of embedding Indigenous perspectives within the
undergraduate nursing curriculum. The experience has been a challenging and
positive one, and the reforms have been supported by a sustainable framework.
This paper outlines how one university faculty is endeavouring to educationally
prepare nursing students to practice with evidence-based transcultural nursing
knowledge based on culture care values, beliefs, and traditional lifeways of
Indigenous people of Australia. As such, the project aims to contribute to the
improvement and promotion of the health and well-being of Indigenous Australians
in culturally and ethnohistorically meaningful ways.
PMID- 17026439
TI - Nursing, Indigenous peoples and cultural safety: so what? Now what?
PMID- 17026438
TI - Is it Aboriginal friendly? Searching for ways of working in research and practice
that support Aboriginal women.
AB - This article describes my journey as a nurse as I search for better ways to work
with urban Aboriginal women. Learning as I build and maintain trusting
relationships with Elders, Aboriginal health professionals and communities has
been an important first step. Incorporating reflective practice, participatory
action research and ethical guidelines has further assisted me to work in more
culturally safe and respectful ways. While there has been increasing recognition
of access and equity issues in Australia's current neo-colonial period, actual
improvements have been very slow to emerge. Meanwhile many Aboriginal people
continue to experience poor levels of health. My hope is that this article can
contribute to the growing body of knowledge that recognises the impact of past
and present colonisation practices and shifts health care towards collaborative
healing and well being models that are more supportive of Aboriginal people and
their needs. The emphasis on Aboriginal women's health rather than mixed gender
health care comes from my experiences in sexual health, where many Australian
Aboriginal women prefer to access 'women only' services.
PMID- 17026448
TI - Postoperative chemotherapy in non-small cell lung cancer: still more questions
than answers.
PMID- 17026449
TI - Gene therapy breakthrough in cancer treatment.
PMID- 17026450
TI - Thalidomide in multiple myeloma: past, present and future.
AB - Thalidomide was introduced in the treatment of multiple myeloma in the late
1990s. Following the initial results, which demonstrated dramatic response rates
in heavily pretreated patients, a number of Phase II studies have confirmed the
efficacy of this agent in relapsed patients. However, a high incidence of side
effects at the dosage initially recommended (400 mg/day) justified further
studies with lower doses of thalidomide given alone or in combination with
dexamethasone or chemotherapy. Thalidomide is currently considered as one of the
most active agents in relapsed myeloma. Recent studies have demonstrated that
thalidomide could also be used as part of frontline therapy. The combination of
thalidomide plus dexamethasone as initial therapy appears to be slightly superior
to dexamethasone alone or to vincristine-doxorubicine-dexamethasone, but with an
increased risk of deep vein thrombosis. Maintenance with thalidomide after
autologous transplantation appears to increase the complete remission rate and to
prolong progression-free survival. The combination of thalidomide plus melphalan
and prednisone is superior to the classical melphalan-prednisone regimen in
elderly patients, and will become the standard of care. Thalidomide has been
registered in the USA in combination with dexamethasone in newly diagnosed
patients, but is not yet registered in the European Union. Its use is currently
challenged by bortezomib and by thalidomide's analog lenalidomide.
PMID- 17026451
TI - Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist.
AB - Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant
deterioration in quality of life. The emetogenicity of the chemotherapeutic
agents, repeated chemotherapy cycles and patient risk factors (female gender,
younger age, alcohol consumption, history of motion sickness) are the major risk
factors for CINV. The use of 5-hydroxytryptamine (5-HT)3 receptor antagonists
plus dexamethasone has significantly improved the control of acute CINV, but
delayed nausea and vomiting remains a clinical problem. A new agent,
palonosetron, has recently been approved for the prevention of acute CINV in
patients receiving either moderately or highly emetogenic chemotherapy and for
the prevention of delayed CINV in patients receiving moderately emetogenic
chemotherapy. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life
and a higher binding affinity than first-generation 5-HT3 receptor antagonists.
In a single dosing study, palonosetron was highly effective in controlling CINV
compared with a single dose of dolasetron or ondansetron in patients receiving
moderately emetogenic chemotherapy. Palonosetron in combination with
dexamethasone demonstrated control of CINV in patients receiving highly
emetogenic chemotherapy. Palonosetron appeared to be as effective in subsequent
courses of chemotherapy compared with the initial course of chemotherapy. There
were no clinically relevant differences seen among palonosetron, ondansetron or
dolasetron in laboratory, electrocardiographic or vital-sign changes, and adverse
reactions reported in the clinical trials were the most common reactions reported
for the 5-HT3 receptor antagonist class. Recent studies using palonosetron-based
anti-emetic combinations in moderately and highly emetogenic chemotherapy, as
well as in the clinical setting of multiple-day chemotherapy, have been reported.
Future studies may consider the use of palonosetron with current and other new
agents and in other clinical settings, such as bone marrow transplantation and
radiation therapy.
PMID- 17026452
TI - Docetaxel in the treatment of gastric cancer.
AB - Docetaxel is part of the standard chemotherapy in breast, non-small cell lung
cancer and androgen-independent metastatic prostate cancer and has recently been
approved for advanced gastric cancer. It demonstrated promising single-agent
efficacy in gastric cancer and was therefore investigated in different
combination regimens. The combination of docetaxel with 5-fluorouracil (5-FU),
capecitabine, irinotecan or cisplatin demonstrated high efficacy. The triple
combination of docetaxel/cisplatin and 5-FU (DCF) was investigated in randomized
Phase II trials and a randomized Phase III study (TAX325). In TAX325, DCF
demonstrated superiority in terms of time to tumor progression, response rate and
survival against a cisplatin/5-FU combination. Docetaxel was therefore approved
for advanced gastric cancer by the US FDA and the European Agency for the
Evaluation of Medicinal Products and will evolve as an integral part of routine
combination regimens against gastric cancer. This review will discuss and
interpret the different Phase II and III trials of docetaxel in gastric cancer.
PMID- 17026453
TI - Is axillary clearance the standard of care for breast cancer patients with
sentinel node involvement?
AB - Sentinel node biopsy (SNB) has become accepted for staging the axilla in early
breast cancer with avoidance of axillary lymph node dissection (ALND) in patients
with negative SNB. For those with positive SNB, the standard surgical management
is ALND; however, this approach is increasingly being challenged. The central
problem is that it is not possible to preoperatively predict whether the SNB will
be positive, and it is even more difficult to determine the likelihood of
nonsentinel node positivity. Various histopathological features indicate
increased risk of nonsentinel node metastasis, including size of SNB metastasis,
presence of lymphovascular invasion, multifocality, number of involved sentinel
nodes and, conversely, the number of negative sentinel nodes. These features have
been combined to produce predictive nomograms but, understandably, these still
lack precision. Presently, the decision to avoid ALND will depend upon both the
clinician and the patient's impression of risk, but if either requires assurance
that no residual axillary disease remains, a completion clearance will be
required.
PMID- 17026454
TI - Tumor dormancy and the role of metastasis suppressor genes in regulating ectopic
growth.
AB - Metastasis, or tumor growth in an ectopic site, may occur several years after
apparently successful treatment of the primary malignancy. Clinical dormancy is
seen in a large number of cancer patients, but once growth in an ectopic site
initiates, current adjuvant therapies are inadequate and the majority of patients
with metastatic disease will die. Many genes may regulate ectopic growth in a
secondary site, including a small subset, termed the metastasis suppressor genes.
Investigation into this class of genes holds promise in terms of gaining a
greater understanding of tumor dormancy and how the process of metastasis may be
naturally inhibited. This review will focus on the role of metastasis suppressor
genes in tumor dormancy. Insights into the metastatic process from studies of
metastasis suppressor genes may lead to novel targets for antimetastatic therapy
through drug-induced reactivation of one or more of these genes and/or their
respective signaling pathways.
PMID- 17026455
TI - Recent advances in the systemic management of colorectal cancer.
AB - Colorectal cancer represents one of the most prevalent malignancies. There have
been considerable improvements in the management of the disease in the last
decade, including advances in surgery. In terms of systemic management, 5
fluorouracil, usually with leucovorin, has remained the mainstay of chemotherapy
for colorectal cancer in both the adjuvant and metastatic settings. In the late
1990s, irinotecan and oxaliplatin reached the clinical arena, and the
introduction of these agents has led to significant improvements in outcomes.
More recently, several biopharmaceuticals, including the monoclonal antibodies
bevacuzimab and cetuximab, have shown promise in clinical studies. These novel
agents are now being incorporated into treatment schedules for colorectal cancer.
This review assesses recent improvements in the systemic management of large
bowel cancer and highlights future challenges.
PMID- 17026456
TI - CXC chemokines and prostate cancer: growth regulators and potential biomarkers.
AB - CXC chemokines are a subset of chemotactic cytokines that possess angiogenic or
angiostatic properties. Using genetically engineered mice lacking the receptors
for these ligands, recent research has demonstrated a significant role for CXC
chemokines in the development and growth of prostate tumors. The Duffy
antigen/receptor for chemokines (DARC), which only binds to CXC chemokines that
have angiogenic properties, is a nonsignaling receptor expressed on erythrocytes
that appears to function by clearing these chemokines from sites of
overproduction. The majority of men of African descent lack this receptor on
their erythrocytes, suggesting that loss of this receptor may contribute to
aggressive tumor phenotypes in these individuals. Thus, CXC chemokines and the
erythrocyte DARC may serve as important growth regulators and biomarkers for
prostate cancer stage and progression.
PMID- 17026457
TI - Novel approaches for the management of patients with Ewing sarcoma.
AB - The concepts of tailored therapy according to genetic profiling and response
based on minimal residual disease evaluation during therapy are attracting
increasing interest in modern clinical oncology. Children with acute
lymphoblastic leukemia are being stratified to various treatment arms with
different intensities according to the genetic characteristics of their leukemia
and their response to therapy as measured by real-time polymerase chain reaction.
Our ability to quickly identify patients with Ewing sarcoma who have a poor
prognosis, and to offer them aggressive therapeutic modalities, such as stem cell
transplantation, may result in an improved cure rate. Based on the knowledge
gained by gene expression profiling and gene silencing techniques we can expect
the emergence of new specific drugs that will target malignant cells without
causing damage to normal tissue, resulting in improved cancer therapy.
PMID- 17026458
TI - Role of surgery in the management of soft tissue tumors.
AB - Pediatric soft tissue sarcomas (STSs), of which rhabdomyosarcoma is the most
common, constitute approximately 5-6% of all cancers in children. Biopsy, being
incisional or rarely excisional, is an essential primary diagnostic step, while
in some cases it may be followed by primary re-excision to establish a correct
diagnosis in which molecular analysis can be helpful. Most European STS treatment
groups favor preoperative chemotherapy, sometimes combined with preoperative
irradiation. Local therapy is essential, in which surgery remains an important
adjunct. However, it has to be applied in a multidisciplinary, combined fashion
in close cooperation with oncologists, pathologists and radiotherapeutists.
Current 5-year survival in rhabdomyosarcoma reaches 60-70% in nonmetastatic cases
and remains below 20% in metastatic situations. Outcome in pediatric
nonrhabdomyosarcoma STS is similar.
PMID- 17026459
TI - New drugs for the treatment of metastatic or refractory soft tissue sarcomas in
children.
AB - Children with relapsed, recurrent or metastatic sarcomas represent a therapeutic
challenge for the pediatric oncologist. Strategies for the development of newer
therapies for children with these sarcomas have, in the past, been histology
specific. For example, drug development in rhabdomyosarcoma has relied upon the
preclinical xenograft model, whereas therapies for pediatric
nonrhabdomyosarcomatous soft tissue sarcomas have mostly been derived from adult
trials. The progress to date and the tools used in the treatment of advanced
pediatric sarcomas will be summarized in this review.
PMID- 17026460
TI - In memoriam: Serafino Zappacosta (1935-2006).
PMID- 17026461
TI - Antigen mimicry, epitope spreading and the pathogenesis of pemphigus.
AB - The molecular and cellular pathogenesis of pemphigus remains unclear. However,
the integrity of intraepidermal and dermoepidermal adhesion appears to be of
special importance, and the presence of antibodies directed against desmosomal
plaque proteins can provoke pemphigus-like pathologies. Antibodies reactive with
various tissue antigens have been detected in pemphigus-like skin conditions. Two
major factors determining the occurrence of different pemphigus subforms are
antigen mimicry and epitope spreading, as these two phenomena underpin antibody
generation in response to different antigens. This multiplicity of target
antigens and antibody responses may lead to diagnostic problems early in the
disease and may also explain the apparent transformation of one disease subform
into another as time progresses.
PMID- 17026462
TI - Human leukocyte antigen class I and MICA haplotypes in a multicase family with
Cladophialophora carrionii chromoblastomycosis.
AB - Previous studies carried out in an endemic semiarid region northwest of Venezuela
at Falcon State have shown a prevalence of 15.4/1000 of chromoblastomycosis
following traumatisms with xenophile vegetation infected with Cladophialophora
carrionii. We performed high-resolution DNA typing of human leukocyte antigen
(HLA)-A, -B and -C and major histocompatibility complex class I chain related
gene A (MICA) alleles and segregation analysis in 49 members of one extended
family with 12 affected individuals, who have lived for approximately 70 years in
this endemic zone. None of the alleles, haplotypes or genotypes is shared by all
the patients. No deviation from the expected HLA haplotype distribution or
association of chromoblastomycosis with HLA-A, -B and -C haplotypes was observed.
Further, a haplotype-sharing transmission/disequilibria testing of 11 nuclear
families did not give enough evidence to claim linkage (P = 0.398), suggesting
that genes located in the short arm of chromosome 6 may not be relevant in the
immune response toward infection with C. carrionii in this Venezuelan endemic
zone. Deleted MICA alleles on HLA-B*4802 haplotypes were present among several
members of the extended family, but only two of them were affected.
PMID- 17026463
TI - Genetic susceptibility to rheumatic heart disease and streptococcal pharyngitis:
association with HLA-DR alleles.
AB - Acute rheumatic fever (ARF) is a systemic inflammatory disease that develops as a
consequence of an exaggerated immune response to group A beta-haemolytic
streptococci, which causes pharyngitis. Major manifestations of ARF include
carditis, arthritis and chorea. Several investigators have attempted to establish
a relation between ARF and human leucocyte antigens (HLA). Heterogeneity in
various studies has been found, although associations with certain antigens were
reported. The aim of this study was to analyse whether HLA-DR alleles play a role
in the resistance or susceptibility to streptococci-related disorders including
rheumatic heart disease (RHD) as a sequela of ARF and recurrent streptococcal
pharyngitis in Turkish patients. The study included 102 patients with RHD, 71
persons with recurrent streptococcal pharyngitis and 130 healthy controls. HLA-DR
alleles were typed by using polymerase chain reaction (PCR)-sequence-specific
primers. Positive association with HLA-DRB1*07 allele was found for RHD when
compared with healthy controls [29.4% vs 13.1%; P < 0.01, P-corrected: P < 0.01,
odds ratio (OR) 2.78, 95% confidence interval (CI) 1.43-5.26] and also for
recurrent streptococcal pharyngitis (26.8% vs 13.1%; P < 0.05, P-corrected: P <
0.05, OR 2.44, 95% CI 1.17-3.56). The frequency of HLA-DRB1*11 allele was
decreased in patients with RHD (23.5% vs 42.3%; P < 0.01, P-corrected: P < 0.01,
OR 0.42, 95% CI 0.24-0.75). Data suggest that HLA-DRB1*07 allele may be a genetic
factor in increasing the susceptibility to develop RHD and recurrent
streptococcal pharyngitis. HLA-DRB1*11 allele seems to be a protective factor
against RHD.
PMID- 17026464
TI - Class II HLA allele polymorphism: DRB1, DQB1 and DPB1 alleles and haplotypes in
the New Zealand Maori population.
AB - Class II alleles of interest to transplantation comprise the DRB1, DQB1 and DPB1
loci. Sequence-based typing was used to determine the class II allelic
variability present in New Zealand Maori, a population with close genetic ties to
Polynesia and known anthropological and linguistic connections to mainland Asia.
The most common DRB1 alleles identified were DRB1*1201, DRB1*110101, DRB1*0403
and DRB1*080302, with frequencies of 21.5%, 14%, 11.25% and 9.25%, respectively.
Standard linkages between the DRB1 locus and the DRB3, 4 and 5 loci were
maintained, with no novel patterns identified. The most common DQB1 alleles
identified were DQB1*030101, DQB1*060101, DQB1*020101, DQB1*0602 and DQB1*050201,
with frequencies of 29.5%, 8%, 7.8%, 6.4% and 6.2%, respectively. The most common
DPB1 alleles identified were DPB1*0501, DPB1*040101 and DPB1*020102, with
frequencies of 40.2%, 28.89% and 15.83%, respectively. A total of 80 estimated
DRB1-DQB1 two-locus haplotypes were detected. DRB1*1201-DQB1*030101 was the most
frequent (15.40%) haplotype, followed by DRB1*110101-DQB1*030101 (9.97%),
DRB1*0403-DQB1*030201 (7.37%) and DRB1*080302-DQB1*060101 (5.96%). The allelic
variation determined is being used in further analysis of the requirement for
bone marrow transplantation in the New Zealand Maori population and has
implications for optimal ethnic donor distribution on the New Zealand Bone Marrow
Donor Registry, anthropological studies and disease association.
PMID- 17026465
TI - Analysis of the expression of HLA class I, proinflammatory cytokines and
chemokines in primary tumors from patients with localized and metastatic renal
cell carcinoma.
AB - Changes in the human leukocyte antigen (HLA) class I expression and cytokine and
chemokine production both by cancer cells and by normal surrounding tissue are
believed to be responsible for immune escape and tumor progression. In this
study, we compared the tumor expression levels of HLA heavy chain (HLAhc), beta-2
microglobulin (beta2m), chemokines (Interferon-gamma-inducible Protein-10 (IP
10), Interferon-inducible T-cell Alpha-Chemoattractant (I-TAC), Stromal cell
Derived Factor-1 (SDF-1), Macrophage Inflammatory Protein-1-alpha (MIP-1-alpha)
and Regulated upon Activation, Normally T-Expressed, and presumably Secreted
(RANTES)) and cytokines (Vascular Endothelial Growth Factor (VEGF), Interferon
gamma (IFN-gamma), Interleukin-10 (IL-10), Tumor Growth Factor-beta (TGB-beta))
in primary tumors and adjacent normal tissues from patients with localized and
metastatic renal cell carcinoma (RCC) using a quantitative real-time polymerase
chain reaction technique. We report that the expression of HLAhc, beta2m and the
studied cytokines and chemokines (except for SDF-1) was significantly higher in
the tumor (29 samples) than in the normal tissue (14 samples). When we compared
the tumor expression levels between patients with localized RCC and patients with
advanced metastatic stage, we found that the messenger RNA expression levels of
HLAhc and beta2m were much lower in patients with metastatic RCC (6 cases) than
in patients with localized cancer (23 cases), with levels similar to those in
normal tissue. This was also confirmed on a protein level by immunohistological
labeling of tumor tissues. Thirty-nine percent of the analyzed RCC tumors showed
partial loss of HLA class I molecules, while 6% of the tumors showed HLA class I
total loss. The expression of IP-10, SDF-1 and VEGF-c was also significantly
lower in patients with advanced tumor, while the IFN-gamma expression in
metastatic RCC was not detectable. Our findings show that primary RCC tumors are
characterized by a high expression of HLAhc and a presence of proinflammatory
mediators and chemokines. We also observed that disease progression and
development of metastasis in RCC are associated with decreased expression of
HLAhc, beta2m, IP-10, SDF-1 and IFN-gamma. This microenvironment may suppress the
cytotoxic response, creating conditions that favor tumor escape and cancer
progression.
PMID- 17026466
TI - Maternal human leukocyte antigen-G polymorphism is not associated with pre
eclampsia in a Chinese Han population.
AB - Pre-eclampsia is a multisystem disorder of pregnancy and remains the leading
cause of both maternal and fetal morbidity and mortality in many countries.
Despite extensive studies, the underlying mechanisms still remain unknown.
Besides its restricted expression in the tissues of placenta and its function in
regulating immune suppression and in ensuring successful invasion of placental
tissues into maternal deciduas, it has been postulated that HLA-G may play a role
in modulation of immune tolerance at the fetal-maternal interface. Aberrant HLA-G
expression may result in pregnancy disorders that are associated with poor
invasion of extravillous cytotrophoblast into maternal spiral arteries, such as
pre-eclampsia. Studies have shown that pre-eclampsia is largely under genetic
control, but genetic mechanisms underlying the disorder have yet to be
determined. In the current study, we focus on the potential role of HLA-G
polymorphism in the pathogenesis of pre-eclampsia. Samples were obtained from
Chinese Han primiparous women with pre-eclampsia and irrelative normal women, and
case-matched placentas were genotyped for the HLA-G polymorphism in the exons 2,
3, and 4, and the 14-base-pair (bp) insertion/deletion polymorphism in the 3'
untranslated region of exon 8 was analyzed separately. The frequency of HLA-G
polymorphism in these samples was not significantly different from those of
normal controls, indicating that maternal HLA-G polymorphism is not associated
with the risk for pre-eclampsia in this Chinese Han population. However, the
maternal 14-bp insertion/deletion polymorphism is ethnically different.
PMID- 17026467
TI - Isolation, molecular cloning and in vitro expression of rhesus monkey (Macaca
mulatta) prominin-1.s1 complementary DNA encoding a potential hematopoietic stem
cell antigen.
AB - Human prominin-1 (CD133 or AC133) is an important cell surface marker used to
isolate primitive hematopoietic stem cells. The commercially available antibody
to human prominin-1 does not recognize rhesus prominin-1. Therefore, we isolated,
cloned and characterized the complementary DNA (cDNA) of rhesus prominin-1 gene
and determined its coding potential. Following the nomenclature of prominin
family of genes, we named this cDNA as rhesus prominin-1.s1. The amino acid
sequence data of the putative rhesus prominin-1.s1 could be used in designing
antigenic peptides to raise antibodies for use in isolation of pure populations
of rhesus prominin-1(+) hematopoietic cells. To the best of our knowledge, there
has been no previously published report about the isolation of a prominin-1 cDNA
from rhesus monkey (Macaca mulatta).
PMID- 17026468
TI - IFN gamma and CXCR-1 gene polymorphisms in idiopathic bronchiectasis.
AB - Idiopathic bronchiectasis is a disease of chronic, bacterial lung infection,
unresolving inflammation and progressive lung damage. Bronchiectasis can be
associated with autoimmune diseases including ulcerative colitis. Defects of both
innate and adaptive immunity have been proposed. The airway inflammation is
characterized by interleukin-8 (IL-8) expression and infiltration by neutrophils
and T cells. Here we investigated two candidate gene polymorphisms that may
contribute to disease susceptibility: a CXCR-1 (+2607 G/C) gene polymorphism that
is implicated in IL-8 binding and neutrophil trafficking as well as the
interferon-gamma (IFNgamma) (+874 T/A) polymorphism which is linked to levels of
IFNgamma production. These polymorphisms were distributed similarly in the
idiopathic bronchiectasis group and controls, suggesting that these two candidate
gene polymorphisms are not associated with disease susceptibility.
PMID- 17026469
TI - Association of interleukin-1 receptor antagonist gene polymorphism and
susceptibility to human brucellosis.
AB - The aim of this study was to determine the influence of the polymorphism within
the intron 2 of the interleukin-1 receptor antagonist gene (IL-1Ra) on the
susceptibility to or development of brucellosis. A total of 255 patients with
brucellosis and 162 healthy volunteers were genotyped for polymorphisms in intron
2 of the IL-1Ra gene. The frequency of allele 2 of the IL-1Ra gene was
significantly higher in patients with brucellosis compared with the controls
(24.5% vs 18.5%, P = 0.03). Although the heterozygosity was more prevalent in
patients than in control individuals, it did not have any statistical
significance (P = 0.1). Alleles 3, 4, and 5 were absent in our study population.
This work is the first that verifies a significant association between genetic
polymorphism of IL-1Ra and susceptibility to brucellosis.
PMID- 17026470
TI - Analysis of the C/T(-1) single nucleotide polymorphism in the CD40 gene in
multiple sclerosis.
AB - The costimulatory CD40-CD40L pathway plays a critical role in the generation and
maintenance of adaptive immune responses. Genetic interference of CD40-CD40L
interactions strongly influences the onset and course in many autoimmune disease
models including experimental autoimmune encephalomyelitis. We analysed the
association of a single nucleotide polymorphism of the CD40 gene (C/T(-1)) in 287
patients with multiple sclerosis (MS) and 184 matched controls. No significant
differences were found in the frequency of the C/T(-1) polymorphism between the
patients with MS and the controls (53% vs 49%) or among different MS subtypes.
Cell surface expression of CD40 did not differ within the different genotypes,
but carriers of the T allele showed a trend for a lower stimulatory index
compared with individuals with the CC genotype. Although these subtle differences
indicate functional consequences in the immune stimulatory capabilities related
to the CD40 C/T(-1) polymorphism, our population-based study found no association
with disease susceptibility or disease course in MS.
PMID- 17026471
TI - Characterization of HLA-B*5516, -B*1313, -B*9512, and -DRB1*1457 alleles
identified in a southwest Chinese population.
AB - The human leukocyte antigen (HLA)-B*5516 allele differs from the B*5502 by a
single 97 T --> C substitution (His to Tyr at position 33) in exon 2. The B*1313
allele results from 419 T --> A and 420 A --> C substitutions, encoding a Leu to
Tyr substitution at 140 in exon 2 of the B*1301 allele. The B*9512 allele differs
from B*1502 by a single 360 G --> C substitution (Gln to His at 120) in exon 3.
The DRB1*1457 allele appears to be a hybrid molecule generated by recombination
between the DRB1*13 and DRB1*14 alleles. The serological equivalents of these new
alleles are HLA-B22, -B13, -B15, and DR13, respectively. Family studies detected
two rare haplotypes: A*11, B*9512, DRB1*14 and A*24, B*52, Cw*07, DRB1*1457,
DRB3*020201, DQB1*050301. The gene frequencies of these alleles in the Chinese
population are less than 0.0001.
PMID- 17026472
TI - The new human leukocyte antigen-A*2631 is characterized by a new HLA-A
polymorphism at amino acid position 62.
PMID- 17026473
TI - A novel HLA-B*44 allele, B*4446, identified by sequence-based typing in a Chinese
donor.
PMID- 17026474
TI - Exon 2 sequence analysis of a novel HLA-DRB1 allele, DRB1*1460.
PMID- 17026475
TI - Exon 2 sequence analysis of a novel HLA-DRB1 allele, DRB1*1520.
PMID- 17026478
TI - Effect of pro-inflammatory stimuli on mucin expression and inhibition by
secretory leucoprotease inhibitor.
AB - Stimuli-induced expression of certain mucin genes has been demonstrated to occur
as a result of ligand-dependent activation of the epidermal growth factor
receptor (EGFR). In particular, MUC5AC expression can be induced by cigarette
smoke, neutrophil elastase and lipopolysaccharide (LPS) following activation of
tumour necrosis factor alpha-converting enzyme. We now show that a large of
number of stimuli relevant to the cystic fibrosis lung - neutrophil elastase,
LPS, Pam3Cys-Ser-(Lys)4 Hydrochloride (a lipopeptide analogue), CpG DNA (which
mimics bacterial DNA) and cystic fibrosis bronchoalveolar lavage fluid - can
activate MUC1 and 2 expression as well as MUC5AC expression in lung epithelial
cells via an EGFR-dependent mechanism. In addition, we demonstrate that the
immunomodulatory anti-protease, secretory leucoprotease inhibitor, can inhibit
stimuli-induced MUC1, 2 and 5AC expression via a mechanism that is primarily
dependent on the inhibition of transforming growth factor type alpha release.
Therefore, mucin gene expression, induced by cystic fibrosis respiratory stimuli,
can be inhibited by secretory leucoprotease inhibitor indicating its potential
importance as an anti-mucin agent in cystic fibrosis and other chronic lung
diseases characterized by mucus hypersecretion.
PMID- 17026479
TI - Histones and histone modifications in protozoan parasites.
AB - Protozoan parasites are early branching eukaryotes causing significant morbidity
and mortality in humans and livestock. Single-celled parasites have evolved
complex life cycles, which may involve multiple host organisms, and strategies to
evade host immune responses. Consequently, two key aspects of virulence that
underlie pathogenesis are parasite differentiation and antigenic variation, both
of which require changes in the expressed genome. Complicating these requisite
alterations in the parasite transcriptome is chromatin, which serves as a
formidable barrier to DNA processes including transcription, repair, replication
and recombination. Considerable progress has been made in the study of chromatin
dynamics in other eukaryotes, and there is much to be gained in extending these
analyses to protozoan parasites. Much of the work completed to date has focused
on histone acetylation and methylation in the apicomplexans and trypanosomatids.
As we describe in this review, such studies provide a unique vantage point of the
evolutionary picture of eukaryotic cell development, and reveal unique phenomena
that could be exploited pharmacologically to treat protozoal diseases.
PMID- 17026480
TI - Does Pseudomonas aeruginosa use intercellular signalling to build biofilm
communities?
AB - Pseudomonas aeruginosa is a Gram-negative bacterial species that causes several
opportunistic human infections. This organism is also found in the environment,
where it is renowned (like other Pseudomonads) for its ability to use a wide
variety of compounds as carbon and energy sources. It is a model species for
studying group-related behaviour in bacteria. Two types of group behaviour it
engages in are intercellular signalling, or quorum sensing, and the formation of
surface-associated communities called biofilms. Both quorum sensing and biofilm
formation are important in the pathogenesis of P. aeruginosa infections. Quorum
sensing regulates the expression of several secreted virulence factors and quorum
sensing mutant strains are attenuated for virulence in animal models. Biofilms
have been implicated in chronic infections. Two examples are the chronic lung
infections afflicting people suffering from cystic fibrosis and colonization of
indwelling medical devices. This review will discuss quorum sensing and biofilm
formation and studies that link these two processes.
PMID- 17026481
TI - Non-lipooligosaccharide-mediated signalling via Toll-like receptor 4 causes fatal
meningococcal sepsis in a mouse model.
AB - Meningococcal lipooligosaccharide (LOS) is a major inflammatory mediator of
fulminant meningococcal sepsis and meningitis with disease severity correlating
with circulating concentrations of LOS and proinflammatory cytokines. In this
study we show that the proinflammatory response to live meningococci in a mouse
model of sepsis involves TLR4, but can develop independently of the expression of
LOS. This is supported by data showing that in vivo an isogenic LOS-deficient
strain, lpxA, induced equivalent disease severity and similar proinflammatory
responses as the serogroup C wild-type parent strain FAM20. This response was
abolished in TLR4-/- mice, and neither the wild-type strain of meningococci nor
the LOS-deficient mutant was able to cause fatal sepsis in these mice. Mouse
survival correlated with low levels of cytokines and chemokines, the chemotactic
complement factor C5a and neutrophil levels in blood at 24 h post infection.
These data suggest that during meningococcal sepsis the recognition of one or
more unidentified non-LOS component(s) by TLR4 is important in stimulating
proinflammatory responses, and that fatality associated with meningococcal sepsis
in mice is induced by the proinflammatory host response.
PMID- 17026482
TI - Haemolysin produced by Vibrio mimicus activates two Cl- secretory pathways in
cultured intestinal-like Caco-2 cells.
AB - Haemolysin (VMH) is a virulent factor produced by Vibrio mimicus, a human
pathogen that causes diarrhoea. As intestinal epithelial cells are the primary
targets of haemolysin, we investigated its effects on ion transport in human
colonic epithelial Caco-2 cells. VMH increased the cellular short circuit current
(Isc), used to estimated ion fluxes, and 125I efflux of the cells. The VMH
induced increases in Isc and 125I efflux were suppressed by depleting Ca2+ from
the medium or by pretreating the cells with BAPTA-AM or by Rp-adenosin 3',5'
cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS). The Cl- channel
inhibitors 4,4'-disothiocyanatostibene-2,2'-disulfonic acid (DIDS),
glybenclamide, and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) suppressed
the VMH-induced increases in Isc and 125I efflux. Moreover, VMH increased the
intracellular concentrations of Ca2+ and cAMP. Thus, VMH stimulates Caco-2 cells
to secrete Cl- by activating both Ca2+ -dependent and cAMP-dependent Cl-
secretion mechanisms. VMH forms ion-permeable pores in the lipid bilayer that are
non-selectively permeable to small ions. However, the ion permeability of these
pores was not inhibited by glybenclamide and DIDS, and VMH did not change the
cell membrane potential. These observations indicate that the pores formed on the
cell membrane by VMH are unlikely to be involved in VMH-induced Cl- secretion.
Notably, VMH stimulated fluid accumulation in the iliac loop test that was fully
suppressed by a combination of DIDS and glybenclamide. Thus, Ca2+-dependent and
cAMP-dependent Cl- secretion may be important therapeutic targets with regard to
the diarrhoea that is induced by Vibrio mimicus.
PMID- 17026483
TI - AMP-activated protein kinase: Role in metabolism and therapeutic implications.
AB - AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge which
becomes activated in situations of energy consumption. AMPK functions to restore
cellular ATP levels by modifying diverse metabolic and cellular pathways. In the
skeletal muscle, AMPK is activated during exercise and is involved in contraction
stimulated glucose transport and fatty acid oxidation. In the heart, AMPK
activity increases during ischaemia and functions to sustain ATP, cardiac
function and myocardial viability. In the liver, AMPK inhibits the production of
glucose, cholesterol and triglycerides and stimulates fatty acid oxidation.
Recent studies have shown that AMPK is involved in the mechanism of action of
metformin and thiazolidinediones, and the adipocytokines leptin and adiponectin.
These data, along with evidence that pharmacological activation of AMPK in vivo
improves blood glucose homeostasis, cholesterol concentrations and blood pressure
in insulin-resistant rodents, make this enzyme an attractive pharmacological
target for the treatment of type 2 diabetes, ischaemic heart disease and other
metabolic diseases.
PMID- 17026484
TI - Role of leptin in the cardiovascular and endocrine complications of metabolic
syndrome.
AB - AIM: To review the potential role of leptin, hyperleptinaemia and leptin
resistance in the cardiovascular and endocrine complications of metabolic
syndrome. METHODS: Review of literature listed in Medline. RESULTS:
Hyperleptinaemia is common in obesity and reflects increased adiposity and leptin
resistance. Nevertheless, leptin resistance may not be complete as several
actions of leptin, such as cardiovascular sympatho-activation, might be preserved
in obese subjects known to be resistant to the metabolic effects of leptin (i.e.
selective leptin resistance). Notably, the renal and sympathetic actions of
leptin may play an important role in the pathogenesis of hypertension related to
obesity and metabolic syndrome. Furthermore, the lipotoxic effect of leptin
resistance may cause insulin resistance and beta cell dysfunction, increasing the
risk of type 2 diabetes. Leptin has also been shown to possess proliferative, pro
inflammatory, pro-thrombotic, and pro-oxidative actions. CONCLUSION:
Hyperleptinaemia and leptin resistance may contribute to hypertension, impaired
glucose metabolism, and pro-atherogenic state in obesity and metabolic syndrome.
PMID- 17026485
TI - Novel insulin analogues and its mitogenic potential.
AB - Insulin analogues were developed to modify the structure of the human insulin
molecule in order to more accurately approximate the endogenous secretion of
insulin. With the help of recombinant technology and site-directed mutagenesis,
the insulin molecule can be modified to either delay or shorten absorption time,
providing better insulin treatment options and facilitating the achievement of
glycaemic goals. Changing the structure of the insulin molecule, however, may
significantly alter both its metabolic and mitogenic activity. Multiple factors
such as residence time on the receptor, dissociation rate, rate of receptor
internalization and the degree of phosphorylation of signalling proteins can
affect the mitogenic potencies of insulin analogues. Changes in the structure of
the insulin have raised concern about the safety of the insulin analogues. For
example, questions have emerged about the relationship between the use of insulin
lispro and insulin glargine and the progression of diabetic retinopathy. Two
studies have shown progression of retinopathy with the use of insulin lispro.
However, others have not confirmed these results, and causality could not be
proven as progression of retinopathy can occur with rapid improvement in
glycaemic control, and methods of assessments among studies were not consistent.
Therefore, we examine the metabolic and mitogenic characteristics of the three
insulin analogues, insulin lispro, insulin aspart and insulin glargine, that are
currently on the market, as well as the two insulin analogues, insulin glulisine
and insulin detemir, that are soon going to be available for clinical use.
PMID- 17026486
TI - Catecholamine storage vesicles and the metabolic syndrome: The role of the
chromogranin A fragment pancreastatin.
AB - Chromogranins or secretogranins (granins), present in secretory granules of
virtually all neuroendocrine cells and neurones, are structurally related
proteins encoded by different genetic loci: chromogranins A and B, and
secretogranins II through VI. Compelling evidence supports both intracellular and
extracellular functions for this protein family. Within the cells of origin, a
granulogenic or sorting role in the regulated pathway of hormone or
neurotransmitter secretion has been documented, especially for chromogranin A
(CHGA). Granins also function as pro-hormones, giving rise by proteolytic
processing to an array of peptide fragments for which diverse autocrine,
paracrine, and endocrine activities have been demonstrated. CHGA measurements
yield insight into the pathogenesis of such human diseases as essential
hypertension, in which deficiency of the catecholamine release-inhibitory CHGA
fragment catestatin may trigger sympathoadrenal overactivity as an aetiologic
culprit in the syndrome. The CHGA dysglycaemic fragment pancreastatin is
functional in humans in vivo, affecting both carbohydrate (glucose) and lipid
(fatty acid) metabolism. Pancreastatin is cleaved from CHGA in hormone storage
granules in vivo, and its plasma concentration varies in human disease. The
pancreastatin region of CHGA gives rise to three naturally occurring human
variants, one of which (Gly297Ser) occurs in the functionally important carboxy
terminus of the peptide, and substantially increases the peptide's potency to
inhibit cellular glucose uptake. These observations establish a role for
pancreastatin in human intermediary metabolism and disease, and suggest that
qualitative hereditary alterations in pancreastatin's primary structure may give
rise to interindividual differences in glucose disposition.
PMID- 17026487
TI - Inhaled insulin delivery--where are we now?
AB - Since 1925, when the concept of treating diabetes with inhaled insulin (INH) was
originally published, a number of clinical challenges have been resolved through
technological advancements. Efforts by pharmaceutical partnerships or individual
companies have resulted in the development of both injection-free devices and
novel insulin formulations. Four different INH systems are now in phase 3 of
clinical development, and several other INH systems are in earlier stages of
clinical study. Clinical data consistently demonstrate that INH therapy is
comparable to subcutaneous (SC) therapy in improving glycaemic control in
patients with either type 1 or type 2 diabetes, generally without greater risk of
overall hypoglycaemia. INH is generally well tolerated and appears to be safe.
Adverse-event profiles for INH therapies are similar to SC insulin therapy, with
the majority of events being reported as being mild to moderate. Long-term safety
studies are ongoing, with emphasis on evaluating the impact of INH therapy on
pulmonary function and immune responses. Although small, reversible decreases in
pulmonary diffusion capacity (DL(co)) and FEV1 have been reported in response to
INH, pulmonary function and structure do not appear to be affected in any
clinically significant way. While insulin antibodies are increased in INH
therapy, these antibodies have not been correlated with haemoglobin A1c (HbA1c),
insulin dosage, hypoglycaemia, pulmonary function or adverse events.
Nevertheless, properly controlled, long-term studies will best answer any
remaining concerns. From the patient's perspective, INH therapy is preferred by
the majority of patients over conventional SC insulin therapy. Studies have shown
that patients prefer INH therapy, because it provides greater lifestyle
flexibility and social acceptability while at the same time avoiding the pain
associated with injection. Thus, after more than 80 years during which the
injection route has been the only means of administering insulin, patients and
physicians may soon avail themselves of another valuable tool in management of
diabetes.
PMID- 17026488
TI - Improvement in glycaemic control with rosiglitazone/metformin fixed-dose
combination therapy in patients with type 2 diabetes with very poor glycaemic
control.
AB - OBJECTIVE: Traditional first-line intervention in patients with type 2 diabetes
and very poor glycaemic control is insulin therapy or high doses of sulfonylureas
if there is no evidence of volume depletion. This study explored the safety and
efficacy of open-label treatment with rosiglitazone and metformin (RSG/MET) fixed
dose combination therapy (AVANDAMET) in patients with type 2 diabetes with very
poor glycaemic control, to better characterize the magnitude of glycated
haemoglobin (A1c) reduction after 24 weeks of therapy. METHODS: In this
multicentre, open-label trial, 190 patients with an A1c greater than 11% or
fasting plasma glucose (FPG) greater than 15 mmol/l were included after failing
to meet glycaemic entry criteria for a primary double-blind, controlled,
randomized study. Unless tolerability issues arose, eligible patients initiated
RSG/MET 4 mg/1000 mg fixed-dose combination therapy and were up-titrated in
increments of 2 mg/500 mg at 4-week intervals to a daily dose of 8 mg/2000 mg or
the maximum tolerated dose. Patients were assessed for efficacy and safety at
five visits over a 24-week period. The primary efficacy end point was change from
baseline in A1c at week 24. Secondary efficacy end points included the proportion
of patients achieving defined A1c targets, change from baseline to week 24 in FPG
and insulin sensitivity. RESULTS: The majority of patients (78%) completed 24
weeks of open-label treatment. At week 24, clinically significant mean reduction
in A1c from 11.8 to 7.8% (mean reduction, 4.0 +/- 2.2%; p < 0.0001) and mean FPG
reduction from 16.9 to 9.2 mmol/l (mean reduction, 7.7 +/- 4.4 mmol/l; p <
0.0001) were observed. A clinically significant reduction in FPG (5.2 mmol/l) was
observed after 4 weeks of treatment with RSG/MET fixed-dose combination therapy.
Despite a high mean baseline A1c of 11.8%, 33% of patients achieved treatment
goal of A1c less than or equal to 6.5% at week 24, and 44% achieved an A1c less
than 7% at week 24. RSG/MET fixed-dose combination was well tolerated, with a low
incidence of hypoglycaemia (2%) and mean increase in weight from baseline of 2.6
+/- 5.2 kg, and few patients withdrew (2.6%) because of an adverse event.
CONCLUSIONS: RSG/MET fixed-dose combination therapy was effective as initial
therapy in patients with type 2 diabetes and very high levels of A1c and/or FPG,
as demonstrated by robust and relatively rapid improvements in glycaemic control.
RSG/MET fixed-dose combination was well tolerated as first-line therapy with no
new tolerability issues identified.
PMID- 17026489
TI - Initial treatment with rosiglitazone/metformin fixed-dose combination therapy
compared with monotherapy with either rosiglitazone or metformin in patients with
uncontrolled type 2 diabetes.
AB - AIM: This study assessed the efficacy and safety of rosiglitazone and metformin
(RSG/MET) fixed-dose combination (AVANDAMET) as initial therapy in patients with
uncontrolled type 2 diabetes compared with monotherapy with either RSG or MET
after 32 weeks of treatment. METHODS: A total of 468 drug-naive patients with
uncontrolled type 2 diabetes were recruited for this multicentre, double-blind
trial if their glycated haemoglobin (A1c) was greater than 7.5%, but less than or
equal to 11%, and their fasting plasma glucose (FPG) was less than or equal to 15
mmol/l. Patients were randomized to 32 weeks of blinded treatment with either
RSG/MET fixed-dose combination (n = 155), MET (n = 154) or RSG (n = 159). The
groups were comparable at baseline, with mean A1c of 8.8% and FPG of 11 mmol/l.
RSG/MET was initiated with a total daily dose of 2 mg/500 mg and could be
increased up to 8 mg/2000 mg; MET therapy began with a total daily dose of 500 mg
and could be increased up to 2000 mg; and RSG treatment began with a total daily
dose of 4 mg and could be increased up to 8 mg. Medication was uptitrated during
on-therapy visits based on failure to attain glycaemic target of mean daily
glucose less than or equal to 6.1 mmol/l (unless at maximum tolerated dose).
Patients were assessed for efficacy and safety at nine visits over a 32-week
treatment period. This was a trial designed to show greater efficacy of RSG/MET
combination therapy compared with MET or RSG monotherapy. The primary end point
was change in A1c from baseline to week 32. Secondary end points included the
proportion of patients achieving recommended A1c and FPG targets for glycaemic
control and change from baseline in FPG, free fatty acid, lipids, insulin,
insulin sensitivity, C-reactive protein and adiponectin. Safety evaluations
included adverse-event (AE) monitoring, changes in weight and clinical laboratory
evaluations. RESULTS: At week 32, RSG/MET showed significant improvements in A1c
from a baseline of 8.9 +/- 1.1% to 6.6 +/- 1.0% at study end, and this 2.3%
reduction was significantly greater than the reductions achieved individually
with MET (-1.8%; p = 0.0008) and RSG (-1.6%; p < 0.0001). The greatest mean
decrease in FPG was seen with RSG/MET (-4.1 mmol/l) and was significant compared
with MET (-2.8 mmol/l; p < 0.0001) and RSG (-2.6 mmol/l; p < 0.0001). Target A1c
of less than or equal to 6.5% and less than 7% were achieved in more patients in
the RSG/MET group (60% and 77%) than with MET (39% and 57%) or RSG (35% and 58%)
respectively. Treatment was well tolerated, with nausea, vomiting and diarrhoea
as the most commonly reported AEs. Oedema was comparable between RSG/MET (6%) and
RSG (7%) and lower in the MET group (3%). No new safety and tolerability issues
were observed in the RSG/MET group. CONCLUSIONS: As first-line therapy in
patients with uncontrolled type 2 diabetes, RSG/MET fixed-dose combination
therapy achieved significant reductions in A1c and FPG compared with either RSG
or MET monotherapy. RSG/MET was generally well tolerated as initial therapy, with
no new tolerability issues identified with the fixed-dose combination.
PMID- 17026490
TI - Effect of nelfinavir on insulin metabolism, proteasome activity and protein
degradation in HepG2 cells.
AB - HIV-1 protease inhibitors have revolutionized the treatment of HIV infection, but
their use has been associated with lipodystrophy and insulin resistance. One
suggestion for this has been the inhibition of insulin-degrading enzyme (IDE). We
have previously demonstrated that insulin, through IDE, can inhibit the
proteasome, thus decreasing cytosolic protein degradation. We examined whether
the protease inhibitor nelfinavir inhibited IDE and its effect on protein
degradation both in vitro and in whole cells. 125I-Insulin degradation was
measured by trichloroacetic acid precipitation. Proteasome activities were
measured using fluorogenic peptide substrates. Cellular protein degradation was
measured by prelabelling cells with 3H-leucine and determining the release of TCA
soluble radioactivity. Nelfinavir inhibited IDE in a concentration-dependent
manner with 50% inhibition at the maximal concentration tested, 100 microm.
Similarly, the chymotrypsin-like and trypsin-like activities of the proteasome
were decreased with an IC50 of approximately 3 microm. The ability of insulin to
inhibit the proteasome was abrogated by nelfinavir. Treatment of HepG2 cells with
50 microm nelfinavir decreased 125I-insulin degradation and increased cell
associated radioactivity. Insulin alone maximally decreased protein degradation
by 15%. Addition of 50 microm nelfinavir inhibited cellular protein degradation
by 14% and blunted the effect of insulin. These data show that nelfinavir
inhibits IDE, decreases insulin's ability to inhibit protein degradation via the
proteasome and provides another possible mechanism for the insulin resistance
seen in protease inhibitor-treated HIV patients.
PMID- 17026491
TI - Weight gain and insulin requirement in type 2 diabetic patients during the first
year after initiating insulin therapy dependent on baseline BMI.
AB - AIM: The aim of this study was to determine differences, if any, in weight gain
and increased insulin requirements in insulin-treated type 2 diabetic patients
with a normal and an elevated body mass index (BMI). METHODS: A total of 192
patients with newly insulinized type 2 diabetes were included in the study. The
patients were divided into three groups: those with BMI <26 (n = 102), BMI 26-30
(n = 50) and those with BMI >30 (n = 40). At the beginning of insulin therapy and
12 months later, we compared HbA1c, BMI and required insulin doses in each group
and evaluated weight gain and the increase in insulin requirement during the
observation period. Moreover, we investigated the influence of additional
metformin therapy on weight gain and insulin requirement. RESULTS: Body weight
increased in the group with normal BMI from 68.8 +/- 9.2 to 70.8 +/- 9.4 kg
(+2.9%) and in the other groups from 79.0 +/- 9.3 to 81.2 +/- 8.4 (+2.8%) and
from 96.2 +/- 11.2 to 99.1 +/- 16.5 kg (+3.0%) respectively. The differences
between the groups were not significant. The insulin requirement increased by 22%
in the normal-weighted group and by 23% in both groups with overweight. The
reduction in mean HbA1c was similar in the three groups (22, 18 and 22%). Under
additional metformin therapy, the increment of insulin requirement of all
patients (n = 40) was significantly lower (11 vs. 26%, p < 0.01), and there was
no significant difference between the groups with different BMIs. During the same
period, the gain in body weight and the decrease of HbA1c were not significantly
different in the patients with and without metformin independent on the BMI.
CONCLUSIONS: The risk for weight gain and increase in insulin requirement is
similar in insulin-treated type 2 diabetic patients with normal and elevated BMI.
Additional metformin therapy reduces insulin requirement in patients with and
without overweight.
PMID- 17026492
TI - Reduced left ventricular mass after treatment of obese patients with sibutramine:
An echocardiographic multicentre study.
AB - AIM: In obesity, left ventricular hypertrophy is frequently observed, especially
in the presence of hypertension. Following body weight reduction, the left
ventricular mass (LVM) is reduced. It is not known to which extent this occurs
after treatment with sibutramine. METHODS: In this multicentre trial, 195 male
and female patients (18-65 years of age, body mass index 30-40 kg/m2) were
treated for 12 weeks with either 15 mg/day sibutramine or placebo. They were
advised to follow mildly hypocaloric reducing diets. Exclusion criteria were
blood pressure values >180/110 mmHg and tachycardia (heart rate > or =100
beats/min). Echocardiography in M-mode was performed to determine LVM as well as
systolic function. RESULTS: Body weight was reduced by 6.9 +/- 0.3 kg under
sibutramine and by 2.1 +/- 0.6 kg under placebo; body fat was reduced by 5.2 +/-
0.4 kg and 1.6 +/- 0.7 kg respectively. In the sibutramine group, LVM was reduced
by 10.9 +/- 24.2 g; LVM indexed for body surface area was reduced by 2.3 +/- 11.8
g/m2 and LVM indexed for body height was reduced by 2.5 +/- 6.0 g/m(2.7). In the
placebo group, LVM and LVM indices were not significantly changed. Changes in LVM
correlated with reductions in body weight and initial LVM but not with changes in
blood pressure or heart rate. CONCLUSIONS: After 3 months of treatment with
sibutramine, obese patients lost about three times as much of body weight and LVM
than patients treated with placebo. Therefore, sibutramine may be recommended not
only to reduce body weight but also to obtain a regression of the LVM in obese
patients with and without hypertension.
PMID- 17026493
TI - Multiple mealtime administration of biphasic insulin aspart 30 versus traditional
basal-bolus human insulin treatment in patients with type 1 diabetes.
AB - AIM: The aim of this study was to compare the effect of multiple mealtime
injections of biphasic insulin aspart 30 (30% fast-acting insulin aspart in the
formulation, BIAsp30) to traditional basal-bolus human insulin regimen (HI) on
glycaemic control in patients with type 1 diabetes. METHODS: Twenty-three
patients (eight women and 15 men) aged 44.8 (20.6-62.5) years (median and range)
with a diabetes duration of 19.5 (1.6-44.6) years completed the study. All
eligible patients were randomly assigned to BIAsp30 thrice daily supplied with
bedtime NPH insulin when necessary, or basal-bolus HI for 12 weeks and then
switched to the alternative regimen for another 12 weeks. The insulin dose
adjustments were made by patients on the basis of advice from a diabetes nurse.
At end of each treatment period, the patients attended two profile days, 1 week
apart for pharmacodynamic and pharmacokinetic assessments. HbA1C was measured at
baseline and at the end of each treatment period. A seven-point self-monitored
blood glucose (SMBG) was obtained twice weekly. RESULTS: In comparison with HI,
multiple mealtime injections of BIAsp30 resulted in a significant reduction in
HbA1C[HI vs. BIAsp30 (%, geometric mean and range): 8.6 (7.4-11.4) vs. 8.3 (6.7
9.8), p = 0.013]. During treatment with BIAsp30, nighttime glycaemic control was
significantly improved. Day-to-day variation in pharmacodynamics and
pharmacokinetics and the rate of hypoglycaemia were not increased with BIAsp30
compared with HI. CONCLUSIONS: In type 1 diabetics, multiple mealtime
administration of BIAsp30 compared with traditional basal-bolus human insulin
treatment significantly improves long-term glycaemic control without increasing
the risk of hypoglycaemia. Despite a higher proportion of intermediate-acting
insulin, thrice-daily injections with BIAsp30 do not increase the day-to-day
variations in insulin pharmacokinetics and pharmacodynamics.
PMID- 17026494
TI - The metabolic syndrome in type 2 diabetes: When does it matter?
AB - AIMS: Young adults with type 2 diabetes (T2Dm) present the clinician with the
problem of when to start therapies for the primary prevention of vascular disease
and how to identify those at most vascular risk. We examine whether the metabolic
syndrome (MetS) can be a useful clinical tool to stratify vascular risk in this
context. METHODS: Data were collected from 5928 subjects with T2Dm, and subjects
were categorized as having MetS by World Health Organization criteria (body mass
index criteria modified for Asians using >23 kg/m2). The prevalence of
macrovascular disease was examined by MetS status and age. RESULTS: The overall
MetS prevalence was 72.3%. MetS was associated with an increased prevalence of
ischaemic heart disease (IHD) (17.2% MetS vs. 11.6% no MetS, p < 0.0001),
coronary artery bypass graft (7.6 vs. 4.7%, p < 0.0003), peripheral vascular
disease (PVD) (4.7 vs. 3.7%, p = 0.08) and stroke (6 vs. 3.9%, p = 0.002) across
all age groups. MetS subjects had an IHD prevalence equivalent to that seen in
subjects who were one decade older without MetS. The most significant impact of
MetS was for the age group of 40-49 years with much lesser impact seen with
progressively increasing age [odds ratio (OR) = 2.1 for IHD in MetS compared with
no MetS at age 40-50 years, p < 0.05; falling progressively to OR = 1.5 at age
>70 years, p > 0.05]. Similar trends were seen for coronary artery by-pass graft
(CABG) and PVD. There was a strong relationship between the number of MetS risk
factors and IHD prevalence (r = 0.99, p = 0.0001). CONCLUSIONS: These data
suggest that MetS is particularly useful in stratifying vascular risk in younger
T2Dm patients and in those with a high number of MetS components. For patients
with MetS, especially those with a full house of MetS risk factors, commencing
risk-lowering interventions 10 years earlier than their MetS-free counterparts
could be considered.
PMID- 17026495
TI - Measurement of liver fat by magnetic resonance imaging: Relationships with body
fat distribution, insulin sensitivity and plasma lipids in healthy men.
AB - AIM: We compared the use of magnetic resonance imaging (MRI) as a test for liver
fat content (LFAT) with proton magnetic resonance spectroscopy (MRS) and
investigated its relationship with body fat distribution, insulin sensitivity,
plasma lipids and lipoproteins. METHODS: LFAT was quantified by MRI and MRS in 17
free-living, healthy men with a wide range of body mass indexes. Fasting
adiponectin was measured by immunoassay and insulin resistance by homeostasis
assessment (HOMA) score. Intraperitoneal, retroperitoneal, anterior subcutaneous
and posterior subcutaneous abdominal adipose tissue masses (ATMs) were determined
by MRI. RESULTS: Measurements of LFAT by MRI and MRS were highly correlated (r =
0.851, p < 0.001). In univariate regression analysis, LFAT by MRI was also
significantly correlated with plasma triglycerides (TGs), insulin, HOMA score,
carbohydrate intake and the masses of all abdominal adipose tissue compartments
(p < 0.05). LFAT was inversely correlated with plasma adiponectin (r = -0.505, p
< 0.05). In multivariate linear regression analysis including plasma adiponectin
and age, intraperitoneal ATM was an independent predictor of LFAT (beta
coefficient = 0.587, p = 0.024). Moreover, intraperitoneal ATM was also an
independent predictor of HOMA score after adjusting for LFAT, plasma adiponectin
and age (beta-coefficient = 0.810, p = 0.010). Conversely, LFAT was a significant
predictor of plasma TG concentration after adjusting for adiponectin,
intraperitoneal ATM, HOMA and age (beta-coefficient = 0.751, p = 0.007). Similar
findings applied with LFAT measured by MRS. CONCLUSIONS: These data suggest that
MRI is as good as MRS to quantify liver fat content. Our data also suggest that
liver fat content could link intraabdominal fat with insulin resistance and
dyslipidaemia.
PMID- 17026496
TI - Obesity risk associated with the K121Q polymorphism of the glycoprotein PC-1
gene.
AB - BACKGROUND: Obesity is considered to be a multifactorial trait resulting from the
combined influence of genetic and environmental determinants. Insulin resistance
plays an important role in the development of obesity. Plasma-cell membrane
differentiation antigene-1 (PC-1) inhibits insulin receptor signalling when
overexpressed and thus causes insulin resistance. PC-1 gene polymorphism might be
associated with adipocyte metabolism disturbance and energy imbalance. The
purpose of this study was to determine whether K121Q polymorphism in PC-1 gene is
involved in obesity susceptibility in Chinese Han population. METHODS: The
genotype of the polymorphism was determined using polymerase chain reaction
restriction fragment length polymorphism analysis for 338 unrelated subjects of
Beijing, China. Their Body mass index (BMI), plasma glucose, total cholesterol,
triglyceride, high-density lipoprotein cholesterol (HDL), free fatty acid (FFA)
and insulin level were measured. Chi-square analyses were applied to test the
significance differences in genotypic and allelic frequencies. Association
studies were undertaken using the t-test and logistic regression analyses.
RESULTS: The obese had significantly higher frequency of KQ/QQ genotype or Q
allele than non-obese in females (26.7% vs. 10.9%, p = 0.014 and 13.3% vs. 5.5%,
p = 0.021). Significant elevation of insulin amongst the Q121 carrier women in
obesity individuals and higher FFA level of Q121 carrier men in non-obese
controls (BMI < or = 23 kg/m2) were observed. Binary logistic regression analysis
revealed that PC-1 genotype together with higher glucose, total cholesterol,
triglyceride and serum HDL were independently associated with the presence of
obesity. CONCLUSIONS: The observed genotype distributions revealed a significant
association of PC-1 K121Q with obesity. PC-1 Q121 carriers are more likely to be
insulin-resistant or get fatter in respect to KK subjects and carriers of the Q
allele are at higher risk for the development of obesity in female.
PMID- 17026497
TI - Variant K of butyrylcholinesterase and risk of early-onset type 1 diabetes
mellitus in Euro-Brazilians.
PMID- 17026498
TI - Re-feeding syndrome following adjustable gastric banding.
PMID- 17026499
TI - Hyperbaric exposure with high oxygen concentration inhibits growth-associated
increase in the glucose level of diabetic Goto-Kakizaki rats.
PMID- 17026500
TI - Runx2 and dental development.
AB - The Runx2 gene is a master transcription factor of bone and plays a role in all
stages of bone formation. It is essential for the initial commitment of
mesenchymal cells to the osteoblastic lineage and also controls the
proliferation, differentiation, and maintenance of these cells. Control is
complex, with involvement of a multitude of factors, thereby regulating the
expression and activity of this gene both temporally and spatially. The use of
multiple promoters and alternative splicing of exons further extends its
diversity of actions. RUNX2 is also essential for the later stages of tooth
formation, is intimately involved in the development of calcified tooth tissue,
and exerts an influence on proliferation of the dental lamina. Furthermore, RUNX2
regulates the alveolar remodelling process essential for tooth eruption and may
play a role in the maintenance of the periodontal ligament. In this article, the
structure of Runx2 is described. The control and function of the gene and its
product are discussed, with special reference to developing tooth tissues, in an
attempt to elucidate the role of this gene in the development of the teeth and
supporting structures.
PMID- 17026501
TI - Detection of pemphigus desmoglein 1 and desmoglein 3 autoantibodies and
pemphigoid BP180 autoantibodies in saliva and comparison with serum values.
AB - Although there is much literature on the detection of pemphigus and pemphigoid
autoantibodies by enzyme-linked immunosorbent assay (ELISA) in serum, nothing is
known about their presence in saliva. The aim of this study was to evaluate the
salivary levels of these autoantibodies in pemphigus and pemphigoid patients.
Autoantibodies against desmoglein3, desmoglein1, and BP180 were assayed, by
ELISA, in serum and saliva samples of patients and healthy controls. The titres
of autoantibodies against Dsg1/3 found in both serum and saliva of pemphigus
patients showed a statistically significant correlation, suggesting that saliva
may be a useful biological material for diagnostic purposes, in monitoring
disease activity, as well as for the early detection of relapses. By contrast,
the titres of autoantibodies against BP180 in the serum and saliva of bullous
pemphigoid patients were not statistically related, and further study of the
usefulness of the BP180 ELISA for saliva in this disease is needed. In addition,
based on our results, the BP180 ELISA with a recombinant NC16a epitope failed to
detect the autoantibodies against BP180 in the serum and saliva of mucous
membrane pemphigoid patients.
PMID- 17026502
TI - Splicing site mutations in dentin sialophosphoprotein causing dentinogenesis
imperfecta type II.
AB - Dentinogenesis imperfecta (DGI) type II (OMIM # 125490) is an inherited disorder
affecting dentin. Defective dentin formation results in discolored teeth that are
prone to attrition and fracture. To date, several mutations have been described
in the dentin sialophosphoprotein (DSPP) gene, causing DGI types II and III and
dentin dysplasia type II. DSPP encodes two proteins: dentin sialoprotein (DSP)
and dentin phosphoprotein (DPP). Here, we describe a mutational analysis of DSPP
in seven Finnish families with DGI type II. We report two mutations and five
single nucleotide polymorphisms. In one family we found a mutation that has been
described earlier in families with different ethnicity, while in six families we
found a novel g.1194C>A (IVS2-3) transversion. Bioinformatic analysis of known
DSPP mutations suggests that DGI type II is usually caused by aberration of
normal splicing.
PMID- 17026503
TI - Oral health, dental anxiety, and behavior management problems in children with
attention deficit hyperactivity disorder.
AB - Attention deficit hyperactivity disorder (ADHD) is a common developmental
disorder. The aim of this study was to investigate whether children with ADHD
have a higher caries prevalence, a higher degree of dental anxiety, or more
dental behavior management problems (BMP) than children of a control group.
Twenty-five children with ADHD and a control group of 58 children, all aged 11
yr, were included in the study. The children underwent a clinical dental
examination, and bitewing radiographs were taken. The parents completed the
Dental Subscale of Children's Fear Survey Schedule (CFSS-DS). Dental records from
the subjects were obtained, and data regarding notes on behavior management
problems (BMP) of the children when between 3 and 10 yr of age were compiled.
Compared with controls, children with ADHD had significantly higher decayed,
missing or filled surfaces (DMFS) (2.0 +/- 3.0 vs. 1.0 +/- 1.5) and significantly
higher decayed surfaces (DS) (1.7 +/- 3.6 vs. 0.5 +/- 0.9). Differences between
the groups regarding CFSS-DS scores were non-significant. In the ADHD group, the
prevalence of BMP increased when the children were between 7 and 9 yr of age. In
conclusion, children with ADHD exhibited a higher caries prevalence, did not
exhibit a higher degree of dental anxiety, and had more BMP than children of a
control group.
PMID- 17026504
TI - Clinical correlates of oral health-related quality of life: evidence from a
national sample of British older people.
AB - This study investigated the relationships between an oral health-related quality
of life (OHRQoL) indicator and specific clinical dental measures, in a national
representative sample of the British older population. A random subsample was
drawn from the free-living sample of the National Diet and Nutrition Survey
(people aged >or= 65 yr). This subsample consisted of 407 dentate and 346
edentate participants, who were clinically examined and interviewed. The OHRQoL
was assessed through the Oral Impacts on Daily Performance (OIDP) indicator.
After adjusting for age, gender, and education, dentate subjects with up to 8
occluding pairs of teeth were 2.66 [95% confidence interval (CI): 1.08, 6.51)
times, and those with up to 2 anterior occluding pairs were 3.00 (95% CI: 1.55,
5.81) times, more likely to report oral impacts when compared with those having
more occluding pairs of teeth. Edentate participants with inadequate denture
adaptation were 1.92 (95% CI: 1.04, 3.53) times, and subjects with inadequate
denture retention were 2.04 (95% CI: 1.13, 3.69) times, more likely to report
oral impacts than the remaining edentate sample in each case. OHRQoL in older
British people is significantly related to the number of occluding pairs of
natural teeth among the dentate and denture quality among the edentate.
PMID- 17026505
TI - Predictors of recall assignment decisions by general dental practitioners
performing routine oral examinations.
AB - The aim of this study was to explore the decision-making behavior of general
dental practitioners (GDPs) in performing routine oral examinations (ROEs).
Change over time was studied by comparing data from a cohort sample of
participants in two surveys in 2000 and 2005. A written questionnaire was sent to
809 dentists (509 responses were obtained) and 475 (61%) were used for analysis.
Of the respondents, 347 also participated in the survey in 2000. The mean number
of diagnostic ROE items per ROE was 6.9 (standard deviation = 1.7). Groups of
GDPs were distinguished based on their answer to the question 'Do you apply for
all patients a fixed recall interval between two successive ROEs?' and four
personal profiles. Of the GDPs, 38.5% (n = 183) assigned fixed recall intervals
(Fxs) for all patients. Individual recall intervals (Ivs) were applied by 61.5%
(n = 292) of GDPs, depending on specific selected patient characteristics and
risk factors. Logistic regression showed that GDPs applying Fxs also used fixed
periods between successive bitewing radiographs. Furthermore, GDPs applying Ivs
conducted more frequent periodontal screening and, in the event of periodontal
problems, were more inclined to prescribe radiographs. Over a 5 yr period, a
shift towards Ivs assignment (from 49% in 2000 to 61.5% in 2005) was found.
Differences in assigned recall intervals (Fxs/Ivs) by GDPs are determined by
three clinical ROE predictors and two GDP profiles. A shift towards a more
individual assessment was found between 2000 and 2005 in the way that Dutch GDPs
are dealing with the assignment of recall interval frequency.
PMID- 17026506
TI - Smoking modulates interferon-gamma expression in the gingival tissue of patients
with chronic periodontitis.
AB - Although interferon-gamma (IFN-gamma) plays a critical role in periodontitis, no
information is available regarding the effect of smoking on this cytokine in the
periodontium. Therefore, this study aimed to evaluate the effect of smoking on
the IFN-gamma levels in gingival tissue from patients with chronic periodontitis.
Sixty-two patients were assigned to three groups: healthy [non-smoking and
periodontally healthy individuals (probing depth or= 5 mm and bleeding on probing;
n = 25)]; and smoking [smokers (>or= 1 pack/day for at least 10 yr) diagnosed
with chronic periodontitis (n = 25)]. Gingival biopsies were analyzed by
quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.
Regardless of smoking status, diseased patients presented higher levels of IFN
gamma than peridontally healthy patients. In sites with comparable types of
periodontitis, smoking increased both protein and mRNA levels of IFN-gamma in
gingival tissue. Within the limits of this study, it can be concluded that
modulation of periodontal tissue destruction by smoking may involve its effect on
IFN-gamma production.
PMID- 17026507
TI - Expression of stem cell factor and its receptor, c-kit, in human oral mesenchymal
cells.
AB - Stem cell factor (SCF) is the pleiotropic ligand for the tyrosine kinase
receptor, c-kit. Ligand and receptor are usually expressed in different cell
types, and binding of SCF to c-kit promotes cell proliferation, differentiation,
and recruitment of progenitor cells in various biologic systems. However, the
localization of these two molecules in cells of the oral cavity has not been
systematically examined. We investigated the expression of SCF and c-kit in human
dental pulp (HDP) cells as well as in human gingival fibroblasts (HGF). Both
alternatively spliced isoforms of SCF were detected (through reverse
transcription-polymerase chain reaction) in RNA obtained from the two cell types.
Western analysis established that both cell types express SCF and/or c-kit,
whereas flow cytometry demonstrated distinct cell populations expressing only the
ligand (SCF), only the receptor (c-kit), or co-expressing the two. HDP cultures
showed higher soluble SCF (sSCF) production associated with faster cell growth,
as compared with HGF cultures. In both cell types, however, sSCF levels appeared
to increase as a result of in vitro aging and/or differentiation.
PMID- 17026508
TI - Composition changes in gingival crevicular fluid during orthodontic tooth
movement: comparisons between tension and compression sides.
AB - The aim of this study was to evaluate whether the application of tension or
compression forces exerted on the periodontium during the early phase of
orthodontic tooth movement is reflected by differences in the composition of the
gingival crevicular fluid (GCF), at the level of interleukin-1beta (IL-1beta),
substance P (SP), and prostaglandin E(2) (PGE(2)). Eighteen children (mean age
10.8 yr) starting orthodontic treatment were included in the study. Molar elastic
separators were inserted mesially to two first upper or lower molars. One of the
antagonist molars served as the control. GCF was collected from the mesial and
distal sites of each molar, before (-7 d, 0 d) and immediately after (1 min, 1 h,
1 d, and 7 d) the placement of separators. The levels of IL-1beta, SP, and PGE(2)
were determined by enzme-linked immunosorbent assay. At the orthodontically moved
teeth, the GCF levels of IL-1beta, SP, and PGE(2) were significantly higher than
at the control teeth in both tension and compression sides, and at almost all
occasions after insertion of separators. The increase, relative to baseline
values, was generally higher in tension sides. For the control teeth, the three
mediators remained at baseline levels throughout the experiment. The results
suggest that IL-1beta, SP, and PGE(2) levels in the GCF reflect the biologic
activity in the periodontium during orthodontic tooth movement.
PMID- 17026509
TI - Interleukin-1alpha and tumor necrosis factor-alpha expression during the early
phases of orthodontic tooth movement in rats.
AB - Remodelling of the periodontium after application of mechanical forces
constitutes the basis of clinical orthodontics and various immunoregulatory
molecules are involved in this process. The aim of this study was to investigate
the expression of the cytokines interleukin-1alpha (IL-1alpha) and tumor necrosis
factor-alpha (TNF-alpha) in dental tissues during the early phases of orthodontic
tooth movement. Eightteen male Wistar rats were used. All maxillary right first
molars were moved orthodontically, with a force of 0.5 N, for 3 h, 1 d, and 3 d.
The contralateral sides served as untreated controls. Parasagittal sections of
the maxillary molars and the surrounding tissues were subjected to
immunohistochemical staining for IL-1alpha or TNF-alpha, and were evaluated with
light microscopy. IL-1alpha and TNF-alpha were expressed in the bone and
periodontal ligament (PDL) along the roots of the orthodontically moved molars
and in the gingiva. Increased expression of both cytokines was observed in the
aforementioned areas after 1 and 3 d of tooth movement. The pulp tissue exhibited
only minor changes in cytokine expression during tooth movement. The results
suggest that mechanical stress results in almost immediate inflammatory reactions
in various dental tissues.
PMID- 17026510
TI - Longitudinal quantification of incipient carious lesions in postorthodontic
patients using a fluorescence method.
AB - The aims of this study were to evaluate the effect of two caries-preventive
programs, and to apply the laser fluorescence method, DIAGNOdent, for
longitudinal quantification of changes in incipient carious lesions. Twelve
subjects with 127 test teeth exhibiting white spot lesions on the buccal surfaces
after completed orthodontic therapy were enrolled in the study. Visual
examination was performed at baseline and after 12 months. The subjects were
divided into two groups: one group received repeated professional tooth cleaning
combined with oral hygiene instruction; and the control group received repeated
oral hygiene instruction only. The white spot lesions were measured by DIAGNOdent
at baseline, and at 3, 6, 9, and 12 months thereafter. There was a significant
difference in the DIAGNOdent readings between the first and the final
evaluations. However, there was no statistically significant difference between
the two treatment groups regarding changes of DIAGNOdent values over time. In
conclusion, it may be possible to use DIAGNOdent for longitudinal quantification
of carious lesions on smooth surfaces over a period of 1 yr under in vivo
conditions. The combination of professional tooth cleaning and oral hygiene
instruction had a similar efficacy to professional tooth cleaning only for
promoting the remineralization of white spot lesions.
PMID- 17026511
TI - Effect of ozone on oral cells compared with established antimicrobials.
AB - Ozone has been proposed as an alternative antiseptic agent in dentistry based on
reports of its antimicrobial effects in both gaseous and aqueous forms. This
study investigated whether gaseous ozone (4 x 10(6) microg m(-3)) and aqueous
ozone (1.25-20 microg ml(-1)) exert any cytotoxic effects on human oral
epithelial (BHY) cells and gingival fibroblast (HGF-1) cells compared with
established antiseptics [chlorhexidine digluconate (CHX) 2%, 0.2%; sodium
hypochlorite (NaOCl) 5.25%, 2.25%; hydrogen peroxide (H(2)O(2)) 3%], over a time
of 1 min, and compared with the antibiotic, metronidazole, over 24 h. Cell
counts, metabolic activity, Sp-1 binding, actin levels, and apoptosis were
evaluated. Ozone gas was found to have toxic effects on both cell types.
Essentially no cytotoxic signs were observed for aqueous ozone. CHX (2%, 0.2%)
was highly toxic to BHY cells, and slightly (2%) and non-toxic (0.2%) to HGF-1
cells. NaOCl and H(2)O(2) resulted in markedly reduced cell viability (BHY, HGF
1), whereas metronidazole displayed mild toxicity only to BHY cells. Taken
together, aqueous ozone revealed the highest level of biocompatibility of the
tested antiseptics.
PMID- 17026512
TI - Three-dimensional finite-element model of the human temporomandibular joint disc
during prolonged clenching.
AB - In the temporomandibular joint (TMJ), overloading induced by prolonged clenching
appears to be important in the cascade of events leading to disc displacement. In
this study, the effect of disc displacement on joint stresses during prolonged
clenching was studied. For this purpose, finite-element models of the TMJ, with
and without disc displacement, were used. Muscle forces were used as a loading
condition for stress analysis during a time-period of 10 min. The TMJ disc and
connective tissue were characterized as a linear viscoelastic material. In the
asymptomatic model, large stresses were found in the central and lateral part of
the disc through clenching. In the retrodiscal tissue, stress relaxation occurred
during the first 2 min of clenching. In the symptomatic model, large stresses
were observed in the posterior part of the disc and in the retrodiscal tissue,
and the stress level was kept constant through clenching. This indicates that
during prolonged clenching the disc functions well in the asymptomatic joint,
meanwhile the retrodiscal tissue in the symptomatic joint is subject to excessive
stress. As this structure is less suitable for bearing large stresses, tissue
damage may occur. In addition, storage of excessive strain energy might lead to
breakage of the tissue.
PMID- 17026514
TI - Growth kinetics of microorganisms isolated from Alaskan soil and permafrost in
solid media frozen down to -35 degrees C.
AB - We developed a procedure to culture microorganisms below freezing point on solid
media (cellulose powder or plastic film) with ethanol as the sole carbon source
without using artificial antifreezes. Enrichment from soil and permafrost
obtained on such frozen solid media contained mainly fungi, and further
purification resulted in isolation of basidiomycetous yeasts of the genera Mrakia
and Leucosporidium as well as ascomycetous fungi of the genus Geomyces. Contrary
to solid frozen media, the enrichment of liquid nutrient solutions at 0 degrees C
or supercooled solutions stabilized by glycerol at -1 to -5 degrees C led to the
isolation of bacteria representing the genera Polaromonas, Pseudomonas and
Arthrobacter. The growth of fungi on ethanol-microcrystalline cellulose media at
8 degrees C was exponential with generation times of 4.6-34 days, while bacteria
displayed a linear or progressively declining curvilinear dynamic. At -17 to -0
degrees C the growth of isolates and entire soil community on 14C-ethanol was
continuous and characterized by yields of 0.27-0.52 g cell C (g of C-substrate)(
1), similar to growth above the freezing point. The 'state of maintenance,'
implying measurable catabolic activity of non-growing cells, was not confirmed.
Below -18 to -35 degrees C, the isolated organisms were able to grow only
transiently for 3 weeks after cooling with measurable respiratory and
biosynthetic (14CO2 uptake) activity. Then metabolic activity declined to zero,
and microorganisms entered a state of reversible dormancy.
PMID- 17026513
TI - Predominance of Roseobacter, Sulfitobacter, Glaciecola and Psychrobacter in
seawater collected off Ushuaia, Argentina, Sub-Antarctica.
AB - Bacterial diversity in sub-Antarctic seawater, collected off Ushuaia, Argentina,
was examined using a culture independent approach. The composition of the 16S
rRNA gene libraries from seawater and seawater contaminated with the water
soluble fraction of crude oil was statistically different (P value 0.001). In
both libraries, clones representing the Alphaproteobacteria, Gammaproteobacteria,
the Cytophaga-Flavobacterium-Bacteroidetes group and unculturable bacteria were
dominant. Clones associated with the genera Roseobacter, Sulfitobacter, Staleya,
Glaciecola, Colwellia, Marinomonas, Cytophaga and Cellulophaga were common to
both the libraries. However, clones associated with Psychrobacter, Arcobacter,
Formosa algae, Polaribacter, Ulvibacter and Tenacibaculum were found only in
seawater contaminated with hydrocarbons (Table 1). Further, the percentage of
clones of Roseobacter, Sulfitobacter and Glaceicola was high in seawater (43%,
90% and 12% respectively) compared to seawater contaminated with hydrocarbons
(35%, 4% and 9% respectively). One of the clones F2C63 showed 100% similarity
with Marinomonas ushuaiensis a bacterium identified by us from the same site.
PMID- 17026515
TI - Hip and non-spine fracture risk reductions differ among antiresorptive agents:
Evidence from randomised controlled trials.
AB - A number of antiresorptive agents reduce the risk of vertebral fractures, but few
have shown consistent effects on hip and other non-spine fractures. Meta-analysis
provides a more precise estimate than individual trials when results are
consistent across pooled trials. Earlier meta-analyses summarised the results for
vertebral and non-spine fractures. New data have emerged for hormone therapy
(HT), alendronate (ALN), risedronate (RIS) and ibandronate (IBN). We surveyed
recent reports of randomised, placebo-controlled trials with non-spine and/or hip
fracture data, and used meta-analysis where appropriate to test for heterogeneity
and derive pooled estimates. The magnitude of effect on hip fracture appears to
be similar to that for non-spine fracture for each drug, but differs among drugs.
Based on the current data, ALN reduces the risk of hip and non-spine fracture by
49-55%, HT by 25-36% and RIS by 26-27%. There is insufficient and/or inconsistent
evidence of an effect on these fractures for IBN, calcitonin and raloxifene.
PMID- 17026516
TI - Lupus erythematosus: clinical and histopathological study of oral manifestations
and immunohistochemical profile of epithelial maturation.
AB - BACKGROUND: Lupus erythematosus (LE) is an autoimmune disease of unknown cause.
Prevalence of oral involvement in patients with LE is uncertain but may vary from
9 to 45% in patients with systemic disease and from 3 to 20% in patients with
chronic cutaneous involvement. METHODS: Incidence of oral lesions of LE and their
clinical aspects were investigated. Their histopathologic features were analyzed,
and the status of epithelial maturation was assessed through the expression
patterns of cytokeratins. RESULTS: Twenty-six patients (from 188 examined)
presented oral lesions of LE. Most of them were females (19) with systemic
disease (11). Clinical aspects of these lesions varied, and lips and buccal
mucosa were most affected. Histologically, lesions revealed lichenoid mucositis
with perivascular infiltrate and thickening of basement. Cytokeratins profile
showed hyperproliferative epithelium, with expression of CK5/6, and CK14 on all
epithelial layers, CK16 on all suprabasal layers and CK10 on prickle cell layers
only. CONCLUSIONS: Oral lesions of LE show a variety of aspects, and their
microscopic features are of a lichenoid mucositis with deep inflammatory
infiltrate. Cytokeratins expression patterns are of hyperproliferative
epithelium, and this phenomenon must be analyzed in relation to the inflammatory
cytokines for a better understanding of the mechanisms of the disease.
PMID- 17026517
TI - Immunoreactivity of CD99 in invasive malignant melanoma.
AB - BACKGROUND: CD99, also known as p30/32, is a glycoprotein product of the MIC2
gene. It was originally utilized in immunohistochemistry as a unique marker for
Ewing sarcoma, other primitive neuroectodermal tumors, and subsequently in other
tumors. Its expression in malignant melanoma (MM) has not been well documented,
with just two isolated cases of MM recently reported. Recent studies have
documented CD99 expression in a significant percentage of atypical fibroxanthomas
(AFX), posing potential diagnostic problems in differentiating these two
entities. As mistaking MM for AFX based on immunohistochemical staining pattern
has significant consequences, we sought to determine the percentage of invasive
MM in our archives that have this staining pattern. METHODS: Seventy-eight cases
of invasive melanoma were retrieved from our files. Each case was stained with
mouse anti-human CD99 and evaluated for membranous expression. RESULTS: Our
evaluation revealed that 47 of 78 MM cases (60%) stain positive for CD99.
CONCLUSION: This study is the first to demonstrate, in a large series, the
prevalence of CD99 expression in primary cutaneous melanoma. Additionally, this
introduces in the histologic differential diagnosis of CD99 expressing dermal
spindle cell lesions.
PMID- 17026518
TI - Stem cell apoptosis in HIV-1 alopecia.
AB - BACKGROUND: Diffuse alopecia occurs in almost 7% of HIV-1-infected patients.
Telogen effluvium is the main pathogenic mechanism involved. Apoptotic
keratinocytes in the outer root sheath at bulge level was described as the most
characteristic histopathologic finding of this kind of hair loss. METHODS: A case
control study was conducted to investigate the occurrence of apoptosis of
follicular stem cells at the bulge in diffuse alopecia of HIV-1 infection. We
applied a double-staining procedure to transverse scalp sections from 15 HIV-1
infected patients and 12 controls, with the monoclonal antibody anticytokeratin
19 as stem cell marker and TUNEL technique to identify apoptosis. RESULTS: Eighty
percent of cases and 25% of controls presented at least one double-stained
follicle. The proportion of positive follicles per section was 48% (+/-7%) for
cases and 26% (+/-13%) for controls. CONCLUSION: Our study demonstrated that
diffuse alopecia related to HIV-1 infection represents a hair cycle disturbance
and that part of the follicular stem cell population become apoptotic in a higher
proportion than normal subjects. We found no cytotoxic folliculitis. Owing to its
cell-cycle interaction and caspase-induction capacities, we propose HIV-1 viral
protein R as a possible follicular stem cell apoptosis inductor.
PMID- 17026519
TI - Type I interferon-associated cytotoxic inflammation in lichen planus.
AB - INTRODUCTION: Lichen planus (LP) is an inflammatory autoimmune skin disease of
unknown origin. Evidence has accumulated that autoreactive cytotoxic CD8(+) T
lymphocytes cause destruction of keratinocytes. Recent studies suggested that
type I interferons (IFNs) play a central role in cytotoxic skin inflammation by
increasing the expression of IP10/CXCR10 and recruiting effector cells via CXCR3.
Here, we investigated whether type I IFNs are also involved in the pathogenesis
of LP. PATIENTS AND METHODS: Skin biopsies of altogether 17 donors (seven LP and
10 healthy controls) were analyzed by immunohistochemistry using monoclonal
antibodies against CD3, CD4, CD8, CD20, CD68, CXCR3, granzyme B, IP10/CXCL10,
CD123, and the MxA protein, which is specifically induced by type I IFNs.
RESULTS: Our analysis revealed a significant expression of the MxA protein in all
LP skin biopsies, indicating involvement of type I IFNs. Expression of MxA was
closely associated with the recruitment of CXCR3(+) and granzyme B(+)
lymphocytes, indicating a Th1-biased cytotoxic immune response. Strong expression
of the CXCR3 ligand, the interferon-inducible protein IP10/CXCL10, links type I
IFN expression and recruitment of CXCR3(+) lymphocytes. Plasmacytoid dendritic
cells (pDCs) appear to be a major source of type I IFNs in LP. DISCUSSION: Our
observations support the hypothesis that lesional type I IFNs produced by pDCs
plays an important role in chronic cytotoxic inflammation of LP by recruiting
cytotoxic effector lymphocytes via IP10/CXCR3 interactions.
PMID- 17026520
TI - Acral keratosis with eosinophilic dermal deposits: a distinctive clinicopatholgic
entity or colloid milium redux?
AB - AIMS: The differential diagnosis of acral keratoses is broad. Encompassing a
variety of infectious, heritable and degenerative disorders, emphasis upon the
clinical setting and histologic subtlety are often required to arrive at the
correct diagnosis. Herein, we report on a series of adult patients who presented
with agminated or solitary papules of the distal finger found on histologic
examination to contain amorphous eosinophilic deposits. RESULTS: The eosinophilic
deposits were found in close proximity to the overlying epithelium and devoid of
apoptotic keratinocytes, plasma cells, or vascular thickening reminiscent of
amyloidosis or hyalinosis cutis. Special and immunostains yielded eosinophilic
material that was elastin and Protein P negative. Despite a similar
histomorphologic appearance to colloid milium, typical clinical features of this
entity were not present. CONCLUSION: The etiologic significance of this condition
is unknown. Potential sources of the material and a discussion of the
differential diagnosis follow.
PMID- 17026521
TI - Merkel cell carcinoma in organ-transplant recipients: report of two cases with
unusual histological features and literature review.
AB - BACKGROUND: Non-melanoma skin cancers are the commonest malignancies after organ
transplantation and are often associated with human papillomavirus (HPV). Merkel
cell carcinoma is an uncommon neuroendocrine skin tumor, of which 67 cases have
been reported up till now, usually briefly, in organ transplant patients.
METHODS: Among a cohort of 2340 organ-transplant recipients, two patients (one
renal, one heart) developed cutaneous Merkel cell carcinomas 5 and 12 years of
post graft, respectively. These were studied histologically and
immunohistochemically, as well as virologically for the presence of HPV. A
thorough literature review of all reported cases of Merkel cell carcinoma
following solid organ transplantation was performed. RESULTS: Despite a typical
immunophenotype, the tumors showed unusual histological features: both were
epidermotropic, and one was intermingled with a bowenoid squamous cell carcinoma.
Search for HPV by immunohistochemistry and PCR proved negative in both cases.
CONCLUSION: In the setting of organ transplantation, Merkel cell carcinoma is
much rarer than other non melanoma skin cancers but may show unusual histologic
features. HPV do not seem to be involved in its pathogenesis.
PMID- 17026522
TI - Nephrogenic fibrosing dermopathy and calciphylaxis with pseudoxanthoma elasticum
like changes.
AB - Nephrogenic fibrosing dermopathy (NFD) and calciphylaxis are rare conditions that
are associated with chronic kidney disease. Histopathologic changes, including
dystrophic dermal calcification, often in association with elastic fibers have
been observed in NFD and calciphylaxis. A pattern of dermal elastic fiber
calcification that mimics pseudoxanthoma elasticum (PXE) has been previously
reported as an incidental finding in the setting of calciphylaxis. Despite a
shared association with renal disease and abnormal calcium deposits, however, NFD
and calciphylaxis are discrete pathologic processes with distinct clinical and
histopathologic features. Criteria for each are reviewed through case
presentation of a patient meeting the clinical and histopathologic criteria for
both NFD and calciphylaxis with histologic features mimicking PXE.
PMID- 17026523
TI - Reactivation of dormant cutaneous Leishmania infection in a kidney transplant
patient.
AB - BACKGROUND: Leishmaniasis is an infection caused by a protozoan parasite
belonging to genus Leishmania and transmitted by the Phlebotomus sandfly.
Clinical presentations of infection include visceral, cutaneous, and
mucocutaneous forms. Leishmaniasis is endemic in Africa, Asia, Europe, South
America, and southern part of North America. This infection is extremely rare in
the US and is mostly found among travelers coming from endemic areas. Cases of
cutaneous and visceral leishmaniasis have been reported in organ transplant
recipients in endemic areas. CASE REPORT: We describe a case of cutaneous
leishmaniasis in a kidney transplant patient, originally from Bolivia, who
resides in the area known to be non-endemic for leishmaniasis and who is known
not to travel within or outside of the US after the transplantation. RESULTS:
Histologic examination of cutaneous lesion revealed extensive subcutaneous
lymphohistiocytic inflammation with clusters of amastigote within histiocytes.
CONCLUSION: To our knowledge, this is the first case of cutaneous leishmaniasis
in a kidney transplant patient residing in the US in an area known to be non
endemic for leishmaniasis, probably after reactivation of a previously dormant
infection acquired outside of the US at least 9 months prior to developing
clinical symptoms.
PMID- 17026524
TI - Pigmented malignant hidroacanthoma simplex mimicking irritated seborrheic
keratosis.
AB - Pigmented variant of malignant hidroacanthoma simplex (PMHS) is very rare. We are
aware of only two reported cases, all arising in pigmented hidroacanthoma simplex
(HS). We report the third case of PMHS arising in a pigmented HS. A 71-year-old
woman presented with a well-demarcated pigmented hyperkeratotic tumor on the
right knee resembling irritated seborrheic keratosis. Histopathologic examination
of the excised tumor revealed intraepidermal proliferation of atypical polygonal
poroid cells forming large, sharply demarcated nests with colonization of
dendritic melanocytes. In addition, there were focal changes of a benign
pigmented HS and syringofibroadenoma. The key diagnostic features of ductal
structures and intracytoplasmic lumina were highlighted by carcinoembryonic
antigen and epithelial membrane antigen immunostaining. PMHS should be
differentiated from irritated seborrheic keratosis, melanoacanthoma, Bowen's
disease and malignant melanoma both clinically and pathologically.
PMID- 17026525
TI - CD-34-reactive trichodiscoma.
PMID- 17026526
TI - The dynamic pattern of glucocorticoid receptor-mediated transcriptional responses
in neuronal PC12 cells.
AB - The aim of the current study was (i) to examine the overlap in the pattern of
glucocorticoid receptor (GR)-mediated transcriptional responses between different
neuronal substrates and (ii) to assess the nature of these responses by
differentiating between primary and downstream GR-responsive genes. For this
purpose, nerve growth factor-differentiated catecholaminergic PC12 cells were
used in which endogenous GRs were activated briefly with a high dose of
corticosterone followed by gene expression profiling 1 and 3 h afterwards using
Affymetrix GeneChips. The results revealed a strikingly similar temporal pattern
to that which was reported previously in hippocampus, with only down-regulated
genes 1 h after GR activation and the majority of genes up-regulated 3 h after GR
activation. Real-time quantatitive PCR of transcripts in cycloheximide-treated
cells showed that all five GR-responsive genes selected from the 1-h time point
were primary responsive, whereas all four GR-responsive genes selected from the 3
h time point were downstream responsive. At the level of individual genes, the
overlap with the previously generated hippocampal data sets was small,
illustrating the cell-type specifity of GR-mediated genomic responses. Finally,
we identified a number of interesting genes, such as SWI/SNF, synaptosomal
associated protein 25 and certain Rab proteins which may play a role in the
effects of glucocorticoids on catecholaminergic neuronal functioning.
PMID- 17026527
TI - Up-regulation of dopamine D(2)L mRNA levels in the ventral tegmental area and
dorsal striatum of amphetamine-sensitized C57BL/6 mice: role of Ca(v)1.3 L-type
Ca(2+) channels.
AB - Dopamine D(2) long (D(2)L) and D(2) short (D(2)S) isoforms of the D(2) receptor
play an important role in psychostimulant-induced neuronal adaptations. In this
study, we used quantitative real-time PCR to specifically amplify these two
splice variants to examine their mRNA expression in the dorsal striatum (dStr),
nucleus accumbens (NAc) and the ventral tegmental area (VTA) of amphetamine
sensitized C57BL/6 mice. We found a significant increase in D(2)L mRNA in the VTA
and dStr of amphetamine-treated mice that positively correlated with the
sensitized locomotor response. We also found a significant increase in D(2)S mRNA
in the VTA. We further examined the role of the Ca(v)1.3 subtype of L-type Ca(2+)
channels in up-regulation of D(2)L and D(2)S mRNA in the VTA. Amphetamine
pretreated Ca(v)1.3 wild-type (Ca(v)1.3(+/+)) mice exhibited sensitized behavior
and a significant increase in D(2)L and D(2)S mRNA compared with saline
pretreated mice Amphetamine-pretreated homozygous Ca(v)1.3 knockout (Ca(v)1.3(-/
)) mice did not exhibit sensitized behavior. There was a significant increase in
D(2)S mRNA, but not D(2)L mRNA. In conclusion, our results find that amphetamine
increases D(2)L mRNA expression in the dStr and the VTA, an adaptation that
correlates with expression of sensitized behavior and dependence on Ca(v)1.3
Ca(2+) channels.
PMID- 17026528
TI - Manipulating Kv4.2 identifies a specific component of hippocampal pyramidal
neuron A-current that depends upon Kv4.2 expression.
AB - The somatodendritic A-current, I(SA), in hippocampal CA1 pyramidal neurons
regulates the processing of synaptic inputs and the amplitude of back propagating
action potentials into the dendritic tree, as well as the action potential firing
properties at the soma. In this study, we have used RNA interference and over
expression to show that expression of the Kv4.2 gene specifically regulates the
I(SA) component of A-current in these neurons. In dissociated hippocampal
pyramidal neuron cultures, or organotypic cultured CA1 pyramidal neurons, the
expression level of Kv4.2 is such that the I(SA) channels are maintained in the
population at a peak conductance of approximately 950 pS/pF. Suppression of Kv4.2
transcripts in hippocampal pyramidal neurons using an RNA interference vector
suppresses I(SA) current by 60% in 2 days, similar to the effect of expressing
dominant-negative Kv4 channel constructs. Increasing the expression of Kv4.2 in
these neurons increases the level of I(SA) to 170% of the normal set point
without altering the biophysical properties. Our results establish a specific
role for native Kv4.2 transcripts in forming and maintaining I(SA) current at
characteristic levels in hippocampal pyramidal neurons.
PMID- 17026529
TI - PACAP and C2-ceramide generate different AP-1 complexes through a MAP-kinase
dependent pathway: involvement of c-Fos in PACAP-induced Bcl-2 expression.
AB - The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP)
inhibits C2-ceramide-induced cell death through blockade of the mitochondrial
apoptotic pathway in rat cerebellar granule neurones. However, the gene induction
processes and transcription factors involved in the anti-apoptotic effect of
PACAP remain unknown. Here, we show that PACAP and C2-ceramide activate activator
protein-1 (AP-1) DNA binding in a dose- and time-dependent manner, but generate
different AP-1 dimers. Thus, PACAP increased the proportion of c-Fos and Jun D
while C2-ceramide increased c-Jun and reduced c-Fos in AP-1 complexes. In
addition, PACAP strongly activated c-Fos gene expression while C2-ceramide
markedly increased c-Jun phosphorylation. The effect of PACAP on c-Fos expression
was blocked by the mitogen-activated protein kinase/extracellular signal
regulated kinase (MEK) inhibitor, U0126, while phosphorylation of c-Jun induced
by C2-ceramide was abrogated by the protein phosphatase 2A (PP2A) inhibitor,
okadaic acid. Transfection of immature granule cells with c-Fos siRNA, which
strongly reduced basal and PACAP-stimulated levels of the protein, totally
prevented the stimulatory effect of PACAP on Bcl-2 expression. The present study
demonstrates that AP-1 complexes containing c-Fos mediate the effect of PACAP on
Bcl-2 gene expression in cerebellar granule neurones. Our data also indicate that
different AP-1 dimers are associated with the pro-apoptotic effect of C2-ceramide
and the anti-apoptotic effect of PACAP.
PMID- 17026530
TI - Dorsal hippocampal administration of triiodothyronine enhances long-term memory
for trace cued and delay contextual fear conditioning in rats.
AB - Thyroid hormones play critical roles in brain maturation and cognitive functions.
The present study investigated the role of thyroid hormone in emotional learning
and memory using trace and delay contextual and cued fear conditioning tasks,
respectively. Rats were administered triiodothyronine (T3) into the dorsal
hippocampal area 10 min before training or immediately after training, and were
scored for freezing behaviour in the same context and in a novel context with and
without an auditory cue that had been paired previously with an aversive
stimulus, a foot shock. Rats administered T3 before and after training both
exhibited significantly increased long-term fear memory in the trace cued and the
delay contextual fear conditioning procedures compared to their control groups.
The T3-administered rats were not significantly different from their respective
controls on the acquisition and short-term fear memory in the trace and delay
fear conditioning tasks. No significant difference on long-term trace contextual
and delay cued fear memory, respectively, was found. These results indicate that
the observed T3-induced enhancement of long-term contextual and cued fear memory
was specific to the hippocampus-dependent conditioning tasks. These findings are
the first to demonstrate that infusion of T3 into the dorsal hippocampus can
improve performance on an emotional memory task.
PMID- 17026531
TI - Nerve growth factor secretion in cultured enteric glia cells is modulated by
proinflammatory cytokines.
AB - The enteric nervous system is composed of neurones and glial cells. These enteric
glia cells (EGC) appear to be essential for the maintenance of gut homeostasis
and mucosal integrity. Neurotrophin nerve growth factor (NGF) also plays an
important role for the gut integrity by regulating sensory and inflammatory
processes in the intestines. Here, we demonstrate EGCs as one source of NGF and
show increased levels of NGF mRNA/protein and tropomyosin receptor kinase A
(TrkA) mRNA in cultured EGCs upon stimulation with proinflammatory cytokines and
lipopolysaccharides. NGF is continuously secreted from cultured EGCs and
proinflammatory cytokines and lipopolysaccharides stimulate the secretion of this
neurotrophin in a time- and dose- dependent manner, whereas interleukin-4 had no
effect on NGF expression. Furthermore, NGF secretion was sustained for more than
12 h after withdrawal of the proinflammatory cytokines, suggesting the
involvement of transcriptional and/or translational processes. Thus, the release
of proinflammatory cytokines can increase NGF secretion by EGCs and leads to a
higher expression of TrkA in EGCs. NGF, in turn, can increase visceral
sensitivity and, on the other hand, appears to improve gut inflammation.
Therefore, NGF secreting EGCs may play a key role in modulating visceral
sensitivity and might be involved in inflammatory processes of the gut.
PMID- 17026532
TI - Chronic prenatal ethanol exposure increases glucocorticoid-induced glutamate
release in the hippocampus of the near-term foetal guinea pig.
AB - Exposure to high cortisol concentration can injure the developing brain, possibly
via an excitotoxic mechanism involving glutamate (Glu). The present study tested
the hypothesis that chronic prenatal ethanol exposure (CPEE) activates the foetal
hypothalamic-pituitary-adrenal axis to produce high cortisol exposure in the
foetal compartment and alters sensitivity to glucocorticoid-induced Glu release
in the foetal hippocampus. Pregnant guinea pigs received daily oral
administration of ethanol (4 g/kg maternal body weight/day) or isocaloric
sucrose/pair-feeding from gestational day (GD) 2 until GD 63 (term, approximately
GD 68) at which time they were euthanised, 1 h after their final treatment.
Adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined
in foetal plasma. Basal and electrically stimulated Glu and gamma-aminobutyric
acid (GABA) efflux in the presence or absence of dexamethasone (DEX), a selective
glucocorticoid-receptor agonist, were determined ex vivo in foetal hippocampal
slices. Glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and N
methyl-D-aspartate (NMDA) receptor NR1 subunit mRNA expression were determined in
situ in the hippocampus and dentate gyrus. In the near-term foetus, CPEE
increased foetal plasma ACTH and cortisol concentrations. Electrically stimulated
glutamate, but not GABA, release was increased in CPEE foetal hippocampal slices.
Low DEX concentration (0.3 microM) decreased stimulated glutamate, but not GABA,
release in both CPEE and control foetal hippocampal slices. High DEX
concentration (3.0 microM) increased basal release of Glu, but not GABA, in CPEE
foetal hippocampal slices. GR, but not MR, mRNA expression was elevated in the
hippocampus and dentate gyrus, whereas NR1 mRNA expression was increased in the
CA1 and CA3 fields of the foetal hippocampus. These data demonstrate that CPEE
increases high glucocorticoid concentration-induced Glu release in the foetal
hippocampus, presumably as a consequence of increased GR expression. These
effects of CPEE, coupled with increased glutamate release and increased NMDA
receptor expression, may predispose the near-term foetal hippocampus to GR and
Glu-NMDA receptor-mediated neurodevelopmental toxicity.
PMID- 17026533
TI - Lack of annexin 1 results in an increase in corticotroph number in male but not
female mice.
AB - Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium
binding proteins with a well demonstrated role in early delayed (30 min to 3 h)
inhibitory feedback of glucocorticoids in the pituitary. We have examined
corticotrophs in wild-type and ANXA1 knockout mice to determine the effects of
lack of ANXA1 in male and female animals. Anterior pituitary tissue from ANXA1
wild-type, heterozygote and null mice was fixed and examined (i) by confocal
immunocytochemistry to determine the number of corticotrophs and (ii) by electron
microscopy to examine the size, secretory granule population and secretory
machinery of corticotrophs. No differences in these parameters were detected in
female mice. In male ANXA1 null mice, there were approximately four-fold more
corticotrophs than in wild-type animals. However, the corticotrophs in ANXA1 null
mice were smaller and had reduced numbers of secretory granules (the reduction in
granules paralleled the reduction in cell size). No differences in the numerical
density of folliculo-stellate, gonadotroph, lactotroph or somatotroph cells were
detected in male ANXA1 null mice. Plasma corticosterone, adrenocorticotrophic
hormone (ACTH) and pituitary pro-opiomelanocortin mRNA were unchanged but
pituitary ACTH content was increased in male ANXA1 null mice. Interleukin (IL)-6
pituitary content was significantly elevated in male and reduced in female ANXA1
null mice compared to wild-type. In conclusion, these data indicate that ANXA1
deficiency is associated with gender-specific changes in corticotroph number and
structure, via direct actions of ANXA1 and/or indirect changes in factors such as
IL-6.
PMID- 17026534
TI - Oestrogen synthesis in the hippocampus: role in axon outgrowth.
AB - Ovarian oestrogens have been postulated to be neuroprotective. It has also been
shown that considerable amounts of oestrogens are synthesised in hippocampal
neurones. In the present study, we focused on a potential role of hippocampus
derived oestradiol compared to gonad-derived oestradiol on axon outgrowth of
hippocampal neurones. To address the role of hippocampus-derived oestradiol, we
inhibited oestrogen synthesis by treatment of neonatal hippocampal cell cultures
with letrozole, a specific aromatase inhibitor. As an alternative, we used siRNA
against steroidogenic acute regulatory protein (StAR). Axon outgrowth and GAP-43
expression were significantly down-regulated in response to letrozole and in
siRNA-StAR transfected cells. The effects after inhibition of oestrogen synthesis
in response to letrozole and in siRNA-StAR transfected cells were reversed by
oestrogen supplementation. No difference was found between ovariectomised
animals, cycling animals at pro-oestrus and ovariectomised and subsequently
oestradiol-treated animals. However, high pharmacological doses of oestradiol
promoted axon outgrowth, which was possible to abolish by the oestrogen receptor
antagonist ICI 182,780. Our results show that oestradiol-induced neurite
outgrowth is very likely mediated by genomic oestrogen receptors and requires
higher doses of oestradiol than physiological serum concentrations derived from
the gonads.
PMID- 17026535
TI - Sexual behaviour induces the expression of activity-regulated cytoskeletal
protein and modifies neuronal morphology in the female rat ventromedial
hypothalamus.
AB - Female sexual behaviour activates a distributed network within the brain,
including the ventrolateral subdivision of the hypothalamic ventromedial nucleus
(vlVMH), as demonstrated by behavioural studies performed in conjunction with the
neuroanatomical analysis of immediate early gene (IEG) expression. However, it
has been difficult to interpret mating-induced IEG expression because the precise
function of many IEGs remains poorly defined. One possible function for genomic
activation of the vlVMH during mating behaviour is to establish synaptic
remodelling. The present experiments tested the hypothesis that sexual behaviour
rapidly induces the expression of a structural protein associated with synaptic
plasticity and ultimately causes morphological changes in the vlVMH. First, the
expression of activity-regulated cytoskeletal protein (Arc), an IEG associated
with neural plasticity, was assayed immunohistochemically in females after
approximately 1 h of mating. The number of Arc-labelled neurones in the vlVMH was
greater in mated females compared to unmated controls. Second, VMH neurones were
biolistically labelled for morphological measurements, including soma size,
dendrite number and length and dendritic spine density. Dendritic spine density
in the vlVMH was significantly reduced 5 days after mating in experienced females
compared to sexually naive females. There were no differences between these
groups in soma size, dendrite length or dendrite number. Collectively, these
studies suggest that mating behaviour produces short-term changes in structural
proteins and long-term, selective changes in dendrite morphology, which then may
influence future behaviours and/or physiology.
PMID- 17026536
TI - Metabolic signals modulate hypothalamic-pituitary-adrenal axis activation during
maternal separation of the neonatal mouse.
AB - The postnatal development of the mouse is characterised by a period of hypo
responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to moderate
stressors. Maternal separation disinhibits this blockade of the HPA axis, but the
mechanism responsible is not clear. The present study examined the influence of
metabolic signals on the central and peripheral components of the HPA axis in
neonatal mice aged 8 days in absence or presence of the mother. Reductions in
plasma glucose and leptin as well as rapid increases in plasma ghrelin were
apparent in the neonate 4 h following maternal deprivation and maximal at 8 h. In
addition, maternal separation induced an increase of neuropeptide Y (NPY) mRNA
expression in the arcuate nucleus, a decrease of corticotrophin-releasing hormone
(CRH) mRNA expression in the paraventricular nucleus and a rise in serum
corticosterone. Pharmacological manipulation of the metabolic signals attenuated
the HPA response to maternal separation. Thus, the rise in plasma corticosterone
induced by maternal separation was ameliorated by prevention of reduction in
blood glucose or blockade of the ghrelin signalling pathway, as were the
hypothalamic changes in NPY and CRH mRNAs. By contrast, leptin treatment did not
affect the HPA axis response to maternal separation. Together these results
suggest that metabolic signals play an important role in triggering the HPA
response of the neonate to maternal separation.
PMID- 17026537
TI - Protective effects of endotoxin in a rat model of chronic inflammation are
accompanied by suppressed secretion of pro-inflammatory cytokines and biphasic
alteration in hypothalamo-pituitary-adrenal axis activity.
AB - We have previously demonstrated that Gram-negative bacterial endotoxin can exert
long-term protective effects against the chronic inflammatory disease adjuvant
arthritis in rats. The present study was designed to investigate the mechanisms
and time-course of hypothalamo-pituitary-adrenocortical (HPA) axis activity and
cytokine secretion underlying this phenomenon. Rats were injected with endotoxin
(lipopolysaccharide) and blood was collected either 7 or 21 days later. Priming
with endotoxin induced a biphasic alteration in secretion of adrenocorticotrophic
hormone and corticosterone in response to a second injection of endotoxin, with
decreased secretion observed after 7 days whereas robust secretion was observed
at 21 days. Seven days following priming with endotoxin, plasma concentrations of
pro-inflammatory cytokines interleukin (IL)-6 and interferon (IFN)-gamma were
reduced by 90%, and tumour necrosis factor (TNF)-alpha by 70%, compared to saline
treated rats, whereas robust secretion of the anti-inflammatory cytokine IL-10
was maintained in both groups. A similar net change favouring an anti
inflammatory cytokine secretory milieu was also observed 21 days following
priming with endotoxin. This study provides evidence that the long-term
protective effects of endotoxin on inflammation are associated with a sustained
reduction in secretion of pro-inflammatory cytokines. HPA axis hypoactivity at 7
days suggests that corticosterone is not involved in suppressing IL-6, IFN-gamma
and TNF-alpha at this time point. Conversely, hypersecretion of corticosterone at
21 days may underlie synchronous suppression of IL-6 and IFN-gamma. These data
provide novel insight into interactions between HPA axis activity and cytokine
secretion following endotoxin priming prior to induction of inflammatory disease.
PMID- 17026538
TI - Laser capture microdissection of plant cells from tape-transferred paraffin
sections promotes recovery of structurally intact RNA for global gene profiling.
AB - Laser capture microdissection and related technologies permit the harvest of
individual cells and cell types. Isolation of either nucleic acids or proteins
from laser-captured cells supports such downstream applications as the
construction of cell-specific cDNA libraries and the profiling of expressed genes
and proteins. The success of these endeavors is dependent upon the yield, purity
and structural integrity of the macromolecules derived from harvested cells.
Here, we report protocols that promote the isolation of structurally intact RNA
from laser-captured cells of paraffin-embedded tissues. The use of a tape
transfer system that obviates the need to wet paraffin sections prior to slide
mounting significantly increases RNA structural quality. Integrity is assessed
directly via electrophoretic separation of picogram-nanogram levels of total RNA
isolated from multiple cell types, including those comprising Arabidopsis ovules,
replums and stamen abscission zones. RNA prepared from specialized cells within
siliques provided targets for profiling the Arabidopsis genome during replum cell
development. Digital northern analysis of transcripts expressed near the
threshold of the system's ability to score signal presence suggests that low
abundance transcripts representing as little as approximately 0.002% of total
mRNA can be reliably detected. Microarray data reveal a significant shift from
primary cell-wall metabolism to lignin biosynthesis in replum tissues during
fruit maturation.
PMID- 17026539
TI - Additive contribution of AMT1;1 and AMT1;3 to high-affinity ammonium uptake
across the plasma membrane of nitrogen-deficient Arabidopsis roots.
AB - In Arabidopsis four root-expressed AMT genes encode functional ammonium
transporters, which raises the question of their role in primary ammonium uptake.
After pre-culturing under nitrogen-deficiency conditions, we quantified the
influx of (15)N-labeled ammonium in T-DNA insertion lines and observed that the
loss of either AMT1;1 or AMT1;3 led to a decrease in the high-affinity ammonium
influx of approximately 30%. Under nitrogen-sufficient conditions the ammonium
influx was lower in Columbia glabra compared with Wassilewskija (WS), and AMT1;1
did not contribute significantly to the ammonium influx in Col-gl. Ectopic
expression of AMT1;3 under the control of a 35S promoter in either of the
insertion lines amt1;3-1 or amt1;1-1 increased the ammonium influx above the
level of their corresponding wild types. In transgenic lines carrying AMT
promoter-GFP constructs, the promoter activities of AMT1;1 and AMT1;3 were both
upregulated under nitrogen-deficiency conditions and were localized to the
rhizodermis, including root hairs. AMT gene-GFP fusions that were stably
expressed under the control of their own promoters were localized to the plasma
membrane. The double insertion line amt1;1-1amt1;3-1 showed a decreased
sensitivity to the toxic ammonium analog methylammonium and a decrease in the
ammonium influx of up to 70% relative to wild-type plants. These results suggest
an additive contribution of AMT1;1 and AMT1;3 to the overall ammonium uptake
capacity in Arabidopsis roots under nitrogen-deficiency conditions.
PMID- 17026540
TI - An eIF4E allele confers resistance to an uncapped and non-polyadenylated RNA
virus in melon.
AB - The characterization of natural recessive resistance genes and virus-resistant
mutants of Arabidopsis have implicated translation initiation factors of the 4E
family [eIF4E and eIF(iso)4E] as susceptibility factors required for virus
multiplication and resistance expression. To date, viruses controlled by these
genes mainly belong to the family Potyviridae. Melon necrotic spot virus (MNSV)
belongs to the family Tombusviridae (genus Carmovirus) and is an uncapped and non
polyadenylated RNA virus. In melon, nsv-mediated resistance is a natural source
of recessive resistance against all strains of MNSV except MNSV-264. Analyses of
chimeras between non-resistance-breaking and resistance-breaking strains have
shown that the avirulence determinant maps to the 3'-untranslated region (3'-UTR)
of the viral genome. Using a combination of positional cloning and microsynteny
analysis between Arabidopsis thaliana and melon, we genetically and physically
delimited the nsv locus to a single bacterial artificial chromosome clone and
identified the melon eukaryotic translation initiation factor 4E (Cm-eIF4E) as a
candidate gene. Complementation analysis using a biolistic transient expression
assay, confirmed Cm-eIF4E as the product of nsv. A single amino acid change at
position 228 of the protein led to the resistance to MNSV. Protein expression and
cap-binding analysis showed that Cm-eIF4E encoded by a resistant plant was not
affected in it's cap-binding activity. The Agrobacterium-mediated transient
expression of the susceptibility allele of Cm-eIF4E in Nicotiana benthamiana
enhanced MNSV-264 accumulation. Based on these results, a model to explain melon
resistance to MNSV is proposed. These data, and data from other authors, suggest
that translation initiation factors of the eIF4E family are universal
determinants of plant susceptibility to RNA viruses.
PMID- 17026541
TI - Advances in equine surgery.
PMID- 17026542
TI - Use of a synthetic bone substitute to retard molariform tooth drift after
maxillary tooth loss in ponies.
AB - OBJECTIVE: To evaluate the effect of alveolar bone substitute on post-extraction
drift of maxillary cheek teeth in ponies. STUDY DESIGN: In vivo longitudinal
experimental study. ANIMALS: Five ponies (5-7 years) with a healthy dentition.
METHODS: Both maxillary 4th premolar teeth (Triadan 08) were surgically removed.
One alveolus was filled with a biocompatible non-resorbable bone substitute
(Bioplant 24), whereas the other healed by second intention. A polyvinylsiloxane
plug and spring wire isolated the bone substitute from the oral environment.
Pathologic changes to dentition and adjacent soft tissue were recorded. Tooth
drift was calculated after 1 and 2 years. RESULTS: At 1 month, bone substitute
material was incorporated into healthy tissue. Tooth drift was observed but
differed significantly between control and treated sides at 2 years (P<.01). For
both techniques, tooth drift differed significantly between years 1 and 2
(P<.001). Total drift in control arcades for year 1 was 10.69+/-2.12 mm and for
year 2 was 9.08+/-0.87 mm, whereas for bone substitute arcades it was 9.90+/-1.60
mm for year 1 and 5.60+/-1.78 mm for year 2. CONCLUSIONS: Partial tooth
replacement therapy after maxillary P4 extraction provided good healing in the
immediate post-surgical phase. Alveolar filling with bone substitute material
significantly slowed post-extraction tooth drift but did not stop it completely.
Clinical Relevance- Important changes occur in equine dentition after maxillary
cheek teeth removal. Further longer term observations are needed to fully
validate study findings.
PMID- 17026543
TI - Levator labii superioris muscle transposition to treat oromaxillary sinus fistula
in three horses.
AB - OBJECTIVE: To describe surgical transposition of the levator labii superioris
muscle to treat oromaxillary sinus fistula in horses. STUDY DESIGN: Clinical
study. ANIMALS: Three horses with chronic oromaxillary sinus fistula. METHODS:
After severing its tendinous insertion, the muscle belly of the levator labii
superioris muscle was retracted and transposed through the oromaxillary sinus
fistula. The tendon exited the oral cavity through a full-thickness buccal
incision created adjacent to the oral end of the fistula and was then tunneled
subcutaneously in a ventral direction before being anchored by sutures to the
cheek tissues. RESULTS: Fistulae healed with few complications and with good
cosmetic and functional results. CONCLUSIONS: Oromaxillary sinus fistula
associated with molariform tooth loss in horses can be treated successfully by
transposition of the levator labii superioris muscle. CLINICAL RELEVANCE:
Transposition of the levator labii superioris muscle should be considered for
resolution of chronic oromaxillary sinus fistula in horses.
PMID- 17026544
TI - Cell growth characteristics and differentiation frequency of adherent equine bone
marrow-derived mesenchymal stromal cells: adipogenic and osteogenic capacity.
AB - OBJECTIVES: To characterize equine bone marrow (BM)-derived mesenchymal stem cell
(MSC) growth characteristics and frequency as well as their adipogenic and
osteogenic differentiation potential. STUDY DESIGN: In vitro experimental study.
ANIMALS: Foals (n=3, age range, 17-51 days) and young horses (n=5, age range, 9
months to 5 years). METHODS: Equine MSCs were harvested and isolated from sternal
BM aspirates and grown up to passage 10 to determine cell-doubling (CD)
characteristics. Limit dilution assays were performed on primary and passaged
MSCs to determine the frequency of colony-forming units with a fibroblastic
phenotype (CFU-F), and the frequency of MSC differentiation into adipocytes (CFU
Ad) and osteoblasts (CFU-Ob). RESULTS: Initial MSC isolates had a lag phase with
a significantly longer CD time (DT=4.9+/-1.6 days) compared with the average DT
(1.4+/-0.22 days) of subsequent MSC passages. Approximately 1 in 4224+/-3265 of
the total nucleated BM cells displayed fibroblast colony-forming activity.
Primary MSCs differentiated in response to adipogenic and osteogenic inductive
conditions and maintained their differentiation potential during subsequent
passages. CONCLUSIONS: The frequency, in vitro growth rate, and adipogenic and
osteogenic differentiation potential of foals and young adult horses are similar
to those documented for BM MSCs of other mammalian species. CLINICAL RELEVANCE:
The results have direct relevance to the use of BM as a potential source of adult
stem cells for tissue engineering applications in equine veterinary medicine.
PMID- 17026545
TI - Comparison of radiography and computed tomography to evaluate
metacarpo/metatarsophalangeal joint pathology of paired limbs of thoroughbred
racehorses with severe condylar fracture.
AB - OBJECTIVE: To compare the orthogonal radiographic (OR) and computed tomographic
(CT) appearance of paired Thoroughbred racehorse limbs with severe condylar
fracture. STUDY DESIGN: In vitro study. SAMPLE POPULATION: Cadaveric paired limbs
with severe condylar fracture (n=11 horses). METHODS: Four standard radiographic
and multiple transverse CT images were obtained of the fractured and
contralateral limbs centering on the metacarpo/metatarsophalangeal (fetlock)
joints. Radiographs and CT images were graded by 4 raters, and interobserver
agreement was calculated. Imaging evaluations were supplemented by fetlock joint
dissection. A consensus description of actual injury and the detection accuracy
of OR and CT for that injury was determined. Results- Rater agreement for OR and
CT for most pathologic features was good or excellent. OR was similar to CT for
the detection of condylar and diaphyseal third metacarpal and metatarsal (MC/MT3)
fractures, diaphyseal fractures of the first phalanx (P1), and fracture location
on the condyle. CT was superior to OR for detection of MC/MT3 proximal fissures
and articular comminution, condylar small cracks and lucencies, and proximal
sesamoid fractures. OR was superior to CT for detection of proximal P1 dorsal
fractures. Both OR and CT were poor at detecting palmar/planter proximal P1
fractures and coalescing cracks in the subchondral bone of MC/MT3. CONCLUSIONS:
CT is better than OR for detection of pathology in limbs with condylar fractures,
but does not detect every pathologic feature. CLINICAL RELEVANCE: CT provides
superior information of pathology in Thoroughbred racehorses with condylar
fractures.
PMID- 17026546
TI - Computed tomographic documentation of a comminuted fourth carpal bone fracture
associated with carpal instability treated by partial carpal arthrodesis in an
Arabian filly.
AB - OBJECTIVE: To report treatment of a unilateral comminuted fourth carpal bone (C4)
fracture associated with carpal instability by partial carpal arthrodesis (PCA)
of the middle carpal joint (MCJ) and carpometacarpal joint (CMCJ). STUDY DESIGN:
Case Report. ANIMALS: An 8-month-old Arabian filly. METHODS: A C4 slab fracture
was diagnosed radiographically; however, fracture comminution was conclusively
diagnosed after computed tomographic (CT) imaging. PCA of the MCJ and CMCJ was
performed with 2 narrow dynamic compression plates. RESULTS: PCA provided
appropriate carpal stability and correct limb alignment immediately after
surgery. Complete bony fusion with substantial carpal flexion and no lameness at
walk or light trot was observed 8 months after surgery. CONCLUSIONS: Carpal CT
was successfully used to define fracture configuration after standard
radiographic examination failed to delineate comminution. PCA was selected
because of joint instability and lateral carpal collapse of MCJ and CMCJ and can
be successfully used to treat comminuted C4 slab fractures associated with carpal
instability. Moderate MCJ osteoarthritis without radiocarpal joint involvement
allows pain-free, substantial carpal flexion and thus, return to low-level
pleasure riding may be possible. CLINICAL RELEVANCE: CT imaging may more
adequately characterize traumatic carpal bone injury, particularly, when carpal
bone fracture configuration cannot be determined on standard radiographs. Early
PCA of the MCJ and CMCJ is an useful alternative to treat comminuted C4 slab
fractures that cannot be reconstructed.
PMID- 17026547
TI - Computer-assisted surgery for screw insertion into the distal sesamoid bone in
horses: an in vitro study.
AB - OBJECTIVE: To compare the precision of computer-assisted surgery with a
conventional technique (CV) using a special guiding device for screw insertion
into the distal sesamoid bone in horses. STUDY DESIGN: In vitro experimental
study. SAMPLE POPULATION: Cadaveric forelimb specimens. METHODS: Insertion of a
3.5 mm cortex screw in lag fashion along the longitudinal axis of intact (non
fractured) distal sesamoid bones was evaluated in 2 groups (8 limbs each): CV and
computer-assisted surgery (CAS). For CV, the screw was inserted using a special
guiding device and fluoroscopy, whereas for CAS, the screw was inserted using
computer-assisted navigation. The accuracy of screw placement was verified by
radiography, computed tomography, and specimen dissection. RESULTS: Surgical
precision was better in CAS compared with CV. CONCLUSION: CAS improves the
accuracy of lateromedial screw insertion, in lag fashion, into the distal
sesamoid bone. CLINICAL RELEVANCE: The CAS technique should be considered for
improved accuracy of screw insertion in fractures of the distal sesamoid bone.
PMID- 17026548
TI - An in vitro biomechanical comparison between prototype tapered shaft cortical
bone screws and AO cortical bone screws for an equine metacarpal dynamic
compression plate fixation of osteotomized equine third metacarpal bones.
AB - OBJECTIVES: To compare biomechanical properties of a prototype 5.5 mm tapered
shaft cortical screw (TSS) and 5.5 mm AO cortical screw for an equine third
metacarpal dynamic compression plate (EM-DCP) fixation to repair osteotomized
equine third metacarpal (MC3) bones. STUDY DESIGN: Paired in vitro biomechanical
testing of cadaveric equine MC3 with a mid-diaphyseal osteotomy, stabilized by 1
of 2 methods for fracture fixation. ANIMAL POPULATION: Adult equine cadaveric MC3
bones (n=12 pairs). METHODS: Twelve pairs of equine MC3 were divided into 3
groups (4 pairs each) for (1) 4-point bending single cycle to failure testing,
(2) 4-point bending cyclic fatigue testing, and (3) torsional single cycle to
failure testing. An EM-DCP (10-hole, 4.5 mm) was applied to the dorsal surface of
each, mid-diaphyseal osteotomized, MC3 pair. For each MC3 bone pair, 1 was
randomly chosen to have the EM-DCP secured with four 5.5 mm TSS (2 screws
proximal and distal to the osteotomy; TSS construct), two 5.5 mm AO cortical
screws (most proximal and distal holes in the plate) and four 4.5 mm AO cortical
screws in the remaining holes. The control construct (AO construct) had four 5.5
mm AO cortical screws to secure the EM-DCP in the 2 holes proximal and distal to
the osteotomy in the contralateral bone from each pair. The remaining holes of
the EM-DCP were filled with two 5.5 mm AO cortical screws (most proximal and
distal holes in the plate) and four 4.5 mm AO cortical screws. All plates and
screws were applied using standard AO/ASIF techniques. Mean test variable values
for each method were compared using a paired t-test within each group.
Significance was set at P<.05. RESULTS: Mean 4-point bending yield load, yield
bending moment, bending composite rigidity, failure load and failure bending
moment of the TSS construct were significantly greater (P<.00004 for yield and
P<.00001 for failure loads) than those of the AO construct. Mean cycles to
failure in 4-point bending of the TSS construct was significantly greater
(P<.0002) than that of the AO construct. The mean yield load and composite
rigidity in torsion of the TSS construct were significantly greater (P<.0039 and
P<.00003, respectively) than that of the AO construct. CONCLUSION: The TSS
construct provides increased stability in both static overload testing and cyclic
fatigue testing. CLINICAL RELEVANCE: The results of this in vitro study support
the conclusion that the EM-DCP fixation using the prototype 5.5 mm TSS is
biomechanically superior to the EM-DCP fixation using 5.5 mm AO cortical screws
for the stabilization of osteotomized equine MC3.
PMID- 17026549
TI - A comparison of laryngoplasty and modified partial arytenoidectomy as treatments
for laryngeal hemiplegia in exercising horses.
AB - OBJECTIVE: To compare upper airway mechanics, arterial blood gases, and tracheal
contamination in horses with induced left laryngeal hemiplegia (recurrent
laryngeal neuropathy [RLN]) treated by laryngoplasty/vocal cordectomy (LPVC) or
modified partial arytenoidectomy (MPA). STUDY DESIGN: Repeated measures under the
following conditions: Control, RLN, LPVC, and MPA. ANIMALS: Six horses. METHODS:
Two trials were conducted under all conditions at 80% and 100% of maximal heart
rate (HR(max)). In Trial 1, arterial blood gases, tracheal and pharyngeal
pressures, and laryngeal videoendoscopy were recorded. In Trial 2, upper airway
pressure and airflow were determined. Tracheobronchial aspirates were performed
after exercise to quantify airway contamination. RESULTS: Compared with control,
RLN significantly increased inspiratory impedance and worsened exercise-induced
hypoxemia. At 80% HR(max), LPVC restored most variables to control values. At
100% HR(max), LPVC improved all variables, but did not restore minute volume,
arterial pH, and PaCO(2). At 80% HR(max), MPA restored all variables except
bicarbonate to control values. At 100% HR(max), MPA improved all variables, but
did not statistically restore minute ventilation or bicarbonate level. Only minor
differences were noted between LPVC and MPA. Both resulted in equivalent tracheal
contamination. CONCLUSIONS: Airway mechanics and arterial blood gas values were
not restored to normal after either LPVC or MPA in horses exercising at HR(max).
This does not affect ventilation at sub-maximal exercise, but has clinical
implications at HR(max). Both procedures diminish normal laryngeal protective
mechanisms. CLINICAL RELEVANCE: At sub-maximal exercise intensities both LPVC and
MPA restore airway ventilation to normal. At maximal exercise the superiority of
LPVC over MPA is slight.
PMID- 17026550
TI - Ventriculocordectomy as the sole treatment for recurrent laryngeal neuropathy:
long-term results from ninety-two horses.
AB - OBJECTIVE: To evaluate the effect ventriculocordectomy (VC) for treatment of
recurrent laryngeal neuropathy (RLN) on exercise performance and owner
satisfaction in a mixed-breed population of horses. STUDY DESIGN: Retrospective
study. ANIMALS: Adult horses (n=92) with a history of abnormal respiratory noise
and RLN. METHODS: Retrospective analysis of horse that had unilateral VC (and
contralateral ventriculectomy in 63 horses) for treatment of idiopathic RLN.
Owners/trainers completed a questionnaire about complications and outcome at
least 1 year after surgery. Performance index was determined using race records
for previously raced Thoroughbreds to evaluate outcome. RESULTS: Clinical signs
included abnormal exercise-induced respiratory noises (noises; 52%), poor
performance (11%), and noises and poor performance (37%). The median preoperative
resting endoscopic grade of laryngeal function was Havemeyer grade III.1 (mild
asymmetry). No discharge from the laryngotomy 1 week postoperatively occurred in
62% horses, 22% coughed after surgery, 66% made no noises, 9% continued to make
noises at the canter, 21% made noise at the gallop, and 4% of owners were unsure
whether noises were present. Ninety-three percent of horses returned to full work
after surgery. Overall, 86% of owners considered the surgery worthwhile, 3% did
not consider it worthwhile, and 11% were unsure. Surgery had a significantly
beneficial effect on the racing performance index in Thoroughbreds (P=.004).
CONCLUSIONS: VC is a useful alternative to laryngoplasty for selected cases of
RLN and is associated with a positive effect on exercise performance, a low
postoperative complication rate, and a high rate of owner satisfaction. CLINICAL
RELEVANCE: Unilateral VC should be considered as a sole treatment in horses with
low grades of RLN.
PMID- 17026551
TI - Standing surgical removal of inspissated guttural pouch exudate (chondroids) in
ten horses.
AB - OBJECTIVE: To report use of a modified Whitehouse approach in standing horses for
management of inspissated guttural pouch empyema. STUDY DESIGN: Retrospective
study. ANIMALS: Adult horses (n=10) with guttural pouch empyema. METHODS:
Inspissated exudate in 1 or both guttural pouches was removed surgically through
a modified Whitehouse approach, with the horses standing and sedated. Medical
records of affected horses were reviewed to determine history; physical,
endoscopic, and radiological examination findings; surgical technique;
complications, and outcome. RESULTS: All horses had purulent nasal discharge; 3
horses had dysphagia, 2 had recurrent laryngeal neuropathy on the side affected
by guttural pouch empyema, and 1 had persistent soft palate displacement.
Inspissated exudate was removed safely without causing apparent discomfort. Eight
horses returned to their previous level of athletic activity after surgery; 1
horse dysphagic before surgery, was euthanatized because of persistent dysphagia
after surgery, and 1 horse died 1 week after surgery for unknown reasons.
Streptococcus equi subsp equi was isolated from the affected guttural pouch of 3
horses. CONCLUSIONS: Inspissated exudate can be removed surgically from the
guttural pouch in standing horses through a modified Whitehouse approach.
CLINICAL RELEVANCE: To eliminate risks associated with general anesthesia and
avoid surgical suite contamination, removal of chondroids can be performed in
standing sedated horses through a modified Whitehouse approach.
PMID- 17026552
TI - Mandibular condylectomy and meniscectomy for the treatment of septic
temporomandibular joint arthritis in a horse.
AB - OBJECTIVE: To report use of mandibular condylectomy for treatment of advanced
degenerative joint disease of the temporomandibular joint (TMJ) caused by sepsis.
DESIGN: Clinical case report. ANIMALS: Two-year-old Noriker filly. METHODS:
Computed tomography (CT) was used to confirm advanced degenerative joint disease
of the left TMJ and for follow-up after mandibular condylectomy and removal of
necrotic meniscus. RESULTS: Painful swelling (3 weeks duration) with drainage
located just caudal to the left lateral canthus of the eye was associated with
atrophy of the left masseter muscle, masticatory problems, and inappetence. There
was incisor malocclusion with a 1.4 cm resting lateral mandibular deviation to
the right and inability to open the mouth more than a few centimeters. Left
mandibular condylectomy combined with meniscectomy and thorough debridement of
the septic left TMJ resulted in resolution of clinical signs and complete return
of function. Streptococcus zooepidemicus, intermediately resistant to penicillin
and subsequently to enrofloxacin, was isolated from the wound. Regeneration of a
mandibular "pseudocondyle" was evident on CT at 4 months. At 4 months and 1 year
the filly had maximal mouth opening >10 cm and no malocclusion. CONCLUSION:
Mandibular condylectomy can be used to facilitate management of septic TMJ
arthritis. There was no radiologic or clinical evidence of TMJ ankylosis >1 year
after meniscal removal. CLINICAL RELEVANCE: Mandibular condylectomy, including
meniscectomy, is an acceptable treatment option for advanced TMJ septic arthritis
and allowed return of normal masticatory function.
PMID- 17026553
TI - Comparison of one-layer (continuous Lembert) versus two-layer (simple
continuous/Cushing) hand-sewn end-to-end anastomosis in equine jejunum.
AB - OBJECTIVE: To evaluate single and double layer end-to-end anastomosis in equine
jejunum. STUDY DESIGN: Experimental in vitro study. ANIMALS: Mid-jejunal sections
from 12 adult horses without gastrointestinal disease. METHODS: Jejunal end-to
end anastomoses were performed by a continuous Lembert pattern or a simple
continuous pattern oversewn with a Cushing pattern. Jejunal segments were
distended with fluid at 1 L/min, and intraluminal pressure at failure, and mode
of failure were recorded. Bursting pressure and bursting wall tension were
calculated. Anastomosis construction time and degree of luminal reduction were
recorded. Results- Single layer anastomoses were constructed in less time than 2
layer anastomoses. Both anastomotic techniques resulted in luminal reduction
compared with control tissue; however, the reduction was smaller with a 1-layer
continuous Lembert anastomosis. No differences were noted in bursting pressure or
bursting wall tension between groups. CONCLUSIONS: Anastomosis using a 1-layer
continuous Lembert pattern resulted in a larger stoma, was faster to perform, and
as strong as a 2-layer anastomosis. CLINICAL RELEVANCE: Use of a 1-layer
continuous Lembert pattern for jejunojejunosotomy may be beneficial by decreasing
anastomosis time and produce a larger stoma than a 2-layer anastomosis.
PMID- 17026554
TI - Initial evaluation of a technique for complete cecal bypass in the horse.
AB - OBJECTIVE: To describe a novel stapling technique for creation of a complete
cecal bypass, without ileal transection in horses. STUDY DESIGN: Experimental
study. ANIMALS: Four adult horses. METHODS: Through a ventral median celiotomy,
jejunocolostomy was made with an intraluminal anastomosis device (ILA-100) and
oversewn with a Cushing pattern to reinforce the staple line. Immediately distal
to the anastomosis, 4 rows of staples were applied using a thoracoabdominal
stapling device (TA-90) to occlude the lumen of the distal jejunum and proximal
ileum. Necropsy exams were performed at least 60 days after surgery. RESULTS: No
intraoperative complications occurred. Cecal bypass was functional in all horses
at necropsy. The most oral staple line across the ileum partially failed in 1
horse; however cecal bypass was functional. CONCLUSIONS: Complete cecal bypass
without ileal transection is a viable alternative to traditional methods of
complete cecal bypass. Two sets of staple lines across the ileum are recommended.
Longer term follow-up is warranted before clinical use of this technique.
CLINICAL RELEVANCE: Cecal bypass without ileal transection is technically simple
and effectively bypasses the cecum. It also should intuitively require less time
and have a reduced risk of contamination compared with complete cecal bypass with
ileal transection.
PMID- 17026555
TI - In vitro evaluation of an inverted end-to-end equine jejunojejunal anastomosis
using skin staples.
AB - OBJECTIVE: To compare functional indices of end-to-end (EEA) jejunojejunal
anastomosis using skin staples in horses with a 2-layer inverting hand-sewn
technique. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Jejunal segments
from 8 fresh equine cadavers. METHODS: For each bowel segment, 2 EEA anastomoses
were created: one 2-layer hand-sewn and one 1-layer using skin staples. Time for
anastomosis creation was recorded and compared. Lumen diameter of each
anastomosis was measured on digital radiographs after intraluminal instillation
of contrast medium and inflation of the jejunal segments to 14 mm Hg. Anastomotic
indices (a compensated measure of stoma diameter) and bursting pressure were
determined. RESULTS: EEA jejunal anastomosis using skin staples was significantly
faster than use of a 2-layer hand-sewn technique. Anastomotic index, a measure of
lumen size, was significantly larger with the skin-staple technique; however, the
bursting pressure of stapled anastomoses was significantly less than for the hand
sewn technique, but the values were well above those reported for other
anastomotic techniques. CONCLUSIONS: An anastomotic technique using skin staples
was easy to learn and perform, effective and faster, and mechanically comparable
with a hand-sewn 2-layer technique. CLINICAL RELEVANCE: The staple technique
could be beneficial in equine gastrointestinal surgery by reducing anastomosis
time, although further in vivo studies are needed to establish clinical safety.
PMID- 17026556
TI - In vitro evaluation of a closed-bowel technique for one-layer hand-sewn inverting
end-to-end jejunojejunosotomy in the horse.
AB - OBJECTIVE: To report a technique for closed-bowel 1-layer inverting end-to-end
jejunojejunal anastomosis in horses. STUDY DESIGN: Experimental study. SAMPLE
POPULATION: Fresh cadaveric jejunal segments from 12 horses. METHODS: For each
bowel segment a 1-layer closed and a 2-layer inverting end-to-end
jejunojejunosotomy was created. Anastomosis construction time and anastomotic
bursting pressure were measured and compared. RESULTS: Closed-bowel anastomosis
was significantly faster to create than a 2-layer technique. Luminal narrowing
(<30%) was similar with both techniques and comparable with other inverting
techniques. Bursting pressure was significantly higher for the 2-layer technique,
although all anastomoses resisted pressures higher than those reported for other
jejunojejunal anastomosis techniques. CONCLUSIONS: A 1-layer hand-sewn, closed,
inverting jejunojejunosotomy using a modified Doyen clamp was easy and faster to
perform, and resulted in functional characteristics similar to, a 2-layer hand
sewn inverting technique. CLINICAL RELEVANCE: A closed, 1-layer inverting
technique could be considered for equine jejunal anastomosis but requires in vivo
evaluation before recommendation for clinical use.
PMID- 17026557
TI - Laparoscopic intestinal exploration and full-thickness intestinal biopsy in
standing horses: a pilot study.
AB - OBJECTIVE: To assess a laparoscopic technique for equine intestinal biopsy. STUDY
DESIGN: Experimental study. ANIMALS: Seven adult horses. METHODS: Food but not
water was withheld for 36 hours before laparoscopy. In 3 horses (group A)
standing, right laparoscopic access to different small intestinal segments was
compared with ventral median celiotomy access. Inaccessible segments were
identified at necropsy. In 4 horses (group B), the feasibility of obtaining full
thickness duodenal and cecal biopsies and any associated morbidity were
evaluated. Biopsy specimens were collected during standing right laparoscopy
using a 2-step procedure and intracorporeal suturing technique, and abdominal
lavage was performed. Horses were monitored clinically and by abdominal fluid
cytology and microbial culture, and repeat laparoscopy was performed on day 6.
RESULTS: Standing right flank laparoscopy provided good observation of small
intestinal segments and enabled manipulation of all but 15-20 cm of the duodenum
and approximately 40 cm more ileum compared with ventral median celiotomy. Group
B horses had no complications, no adhesions, and no bacterial growth from
peritoneal fluid samples. None of the horses had signs of abdominal pain.
CONCLUSION: A 2-stage intestinal biopsy technique performed during standing,
right flank laparoscopy may be a safe alternative to exploratory celiotomy and
biopsy in normal horses. CLINICAL RELEVANCE: Right flank laparoscopy allows
biopsy of intestinal segments including duodenum and 50% more of the ileum than
is accessible by ventral median celiotomy. This technique should be evaluated in
clinical patients.
PMID- 17026558
TI - Cytomegalovirus colitis complicating inflammatory bowel disease.
AB - When patients with inflammatory bowel disease (IBD) are admitted to the hospital
with a flare of acute severe colitis, the possibility of a concurrent
cytomegalovirus (CMV) infection causing or worsening the colitis is often
considered. IBD patients are usually immunosuppressed, and therefore presumably
at increased risk for active CMV infection and disease. Multiple techniques are
used to diagnose CMV infection, including endoscopy, histology, serology, viral
culture, CMV antigen testing, and CMV DNA testing. Immunohistochemistry (IHC)
performed on colon biopsy specimens with monoclonal antibodies directed against
CMV immediate early antigen is considered by most to be the current gold standard
for diagnosis. The prevalence of CMV infection in acute severe colitis appears to
be 21-34%, and the prevalence of CMV infection in the steroid refractory subgroup
of these patients is 33-36%. After antiviral therapy, colitis remission rates in
IBD patients with CMV infection range from 67% to 100%, though CMV histological
infection or the presence of circulating virus alone is not always associated
with steroid resistance, and may not require antiviral therapy.
PMID- 17026559
TI - The impact of colon preparation timing on colonoscopic detection of colorectal
neoplasms--a prospective endoscopist-blinded randomized trial.
AB - OBJECTIVES: Timing of colon preparation might influence the cleansing condition
of the colon and therefore affect the quality and diagnostic yield of
colonoscopy. This study compared two different timings of colon preparation to
assess the efficacy of colon cleansing and diagnostic yield of colorectal
neoplasms during colonoscopy. METHODS: One hundred twenty-one eligible subjects
who had colorectal neoplasms detected at a screening colonoscopy were randomly
assigned to receive colon preparation with polyethylene glycol electrolyte lavage
solution (PEG-ELS) either on the day of (on the day group) or the night before
(previous night group) a second colonoscopy. The condition of colon preparation
and the diagnostic yield of colorectal neoplasms were recorded and compared
between the two groups for the initial and second colonoscopies. RESULTS: Fifty
nine subjects received colon preparation on the night before and 60 subjects
received colon preparation the day of a second colonoscopy. Colon preparation for
the second colonoscopy was better in the on-the-day group than in the previous
night group (P= 0.003). Colon preparation for the second colonoscopy was better
for each group in comparison with the initial colonoscopy (P < 0.0001). An
interobserver variability analysis using 20 randomly selected colonoscopies from
the two groups revealed good correlation among four colonoscopists. More lesions
were detected in group A during the second colonoscopy (P= 0.028). CONCLUSION:
Colon preparation on the day of colonoscopy has a better cleansing quality and
higher diagnostic yield. Subjects who had lesions detected during the initial
screening colonoscopy had better colon cleansing for the second colonoscopy
regardless of the timing of preparation.
PMID- 17026560
TI - A prospective, randomized comparison of adrenaline injection in combination with
detachable snare versus adrenaline injection alone in the prevention of
postpolypectomy bleeding in large colonic polyps.
AB - OBJECTIVES: Our study sought to compare the efficacy of adrenaline injection in
combination with detachable snare versus adrenaline injection alone in the
prevention of postpolypectomy bleeding in large colonic polyps. METHODS: At the
time of colonoscopy, patients with at least one colonic polyp > or =2 cm were
randomized to receive treatment either by the injection of a 1:10.000 solution of
adrenaline and the position of a detachable snare followed by a conventional
snare polypectomy (group A) or injection of adrenaline followed by a conventional
snare polypectomy (group B). A total of 159 consecutive patients were randomly
assigned to one of the above groups. Out of them, 84 patients (47 men, 37 women,
mean age 61 yr) were assigned to group A and 75 (37 men, 38 women, mean age 64
yr) to group B. Early (<24 h) and late (>24 h-30 days) bleeding complications
were assessed. RESULTS: Overall bleeding complications occurred in 10/159 (6.2%)
of the patients. There were two cases of bleeding in group A (2.3%), and eight in
group B (10.6%) (P= 0.04). The number of early bleeding episodes was
significantly reduced in group A patients (1 case) compared to that of group B (7
cases) (P= 0.02). In contrast, there was no significant difference between group
A and B as far as late bleeding is concerned. CONCLUSIONS: Our data suggest that
the use of adrenaline injection in combination with detachable snare may
significantly decrease the number of early postpolypectomy bleeding episodes in
patients with large colonic polyps.
PMID- 17026561
TI - Incidence and management of primary malignant small bowel cancers: a well-defined
French population study.
AB - BACKGROUND AND AIM: Few data are available from population-based statistics on
small bowel cancers. The aim of this study was to report on their incidence and
management. METHODS: Data were obtained from the population-based Digestive
Cancer Registry of Burgundy over a 26-yr period. Incidence rates were calculated
by gender, age group, histological type, and 5-yr period. Treatment and stage at
diagnosis were investigated. Prognosis was determined using crude and relative
survival rates. A multivariate relative survival analysis was performed. RESULTS:
Age-standardized incidence rates were 1.2/100,000 inhabitants for men and
0.8/100,000 inhabitants for women. The mean 5-yr variation in incidence were,
respectively, +46.7% (P < 0.01) and + 53.2% (P < 0.05). There were four main
histological types: adenocarcinoma (40.4%), malignant endocrine tumors (30.5%),
lymphoma (20.1%), and sarcoma (9.0%). Resection for cure was performed in 56.6%
of the cases. Cancer was not extending beyond the organ in 33.2% of the cases,
was associated with lymph node metastasis in 32.1%, and with distant metastasis
or unresectability in 34.7%. The 5-yr relative survival rate was 37.4%. It varied
between 56.8% for endocrine tumors and 17.8% for sarcoma. In the multivariate
analysis, age, histology, and stage at diagnosis significantly influenced the
prognosis. CONCLUSIONS: Small bowel cancers represent a heterogeneous group of
rare tumors. Prognosis at a population level is worse than in hospital series. In
the short term, new therapeutic possibilities represent the best way to improve
prognosis.
PMID- 17026562
TI - Agreement between rapid onsite and final cytologic interpretations of EUS-guided
FNA specimens: implications for the endosonographer and patient management.
AB - BACKGROUND: The practice of onsite cytology interpretation varies across
endoscopic ultrasound (EUS) programs in the United States and Europe. The value,
reliability, and agreement of rapid onsite evaluation (ROSE) compared with final
interpretation and its impact on patient management remain largely unknown. We
compared agreement between ROSE of EUS-FNA (endoscopic ultrasound-guided fine
needle aspiration) specimens with final cytology interpretation and their
respective operating characteristics. METHODS: We prospectively evaluated
consecutive EUS-FNA specimens obtained by a single endosonographer in the
presence of an attending cytopathologist (July 2000-November 2002). The
"agreement" between ROSE and final cytology interpretation was assessed by the
"kappa" statistic. The frequency and possible reasons for discrepancy between
ROSE and final cytologic interpretation were determined. RESULTS: A total of 540
patients (median age 63 yr, 77% white) underwent EUS-FNAs of 656 lesions. These
included lymph nodes (LNs, N = 248), solid pancreatic masses (SPMs, N = 229),
cystic pancreatic masses (CPM, N = 57), mural lesions (41), bile duct/gallbladder
(N = 28), liver (N = 17), mediastinum/lung (N = 17), adrenal (N = 15), spleen (N
= 3), and kidney (N = 1). Data were available for onsite evaluation in 607
lesions. Initial cytology was benign (N = 243), atypical (N = 23), suspicious
(24), malignant (300), and indeterminate (N = 17). Out of the 243 benign lesions
interpreted by onsite evaluation, five lesions (2.1%) were upgraded to be
malignant or suspicious for malignancy on final cytology report. Of the 300
lesions initially reported malignant on ROSE, 294 (98%) remained malignant on the
final cytology. There was an excellent agreement between ROSE and final cytologic
evaluation (kappa = 84.0%, 95% CI 80.2-87.7), Compared with the true final
status, accuracy for final interpretation was slightly higher than for ROSE but
was not statistically significant (95.8%vs 93.9%). Scant cellularity remained the
most frequent reason for discrepancy, accounting for 21 of 51 discrepancies
(41%). Other reasons for discrepancy included: cases requiring an
intradepartmental consultation (22%), cases requiring ancillary studies (12%),
intra-observer variability (10%), and challenging diagnosis (10%). In three
cases, (6%) we were unable to determine the possible reason for discrepancy.
CONCLUSION: ROSE of EUS-FNA specimens is highly accurate compared with final
cytologic evaluation. Because the diagnosis of malignancy rarely changes,
informing our patients and their families and our referring physicians of a
cancer diagnosis significantly reduces physician work load and expedites patient
management. The majority of discrepancies are related to the nature of the lesion
either because it sheds few cells, has challenging morphology, and/or requires
additional ancillary studies.
PMID- 17026563
TI - Microsatellite instability accounts for tumor site-related differences in
clinicopathologic variables and prognosis in human colon cancers.
AB - OBJECTIVE: Colon cancers with high frequency microsatellite instability (MSI-H)
are preferentially located in the proximal colon. Given that 15-20% of sporadic
colon cancers are MSI-H, we determined whether tumor site-specific differences in
clinicopathological variables, biomarkers, and prognosis are due to inclusion of
MSI-H cases. METHODS: TNM stage II and III primary colon carcinomas (N = 528)
from patients enrolled in 5-fluorouracil-based adjuvant trials were analyzed for
MSI using 11 microsatellite markers. Immunostaining for DNA mismatch repair
(hMLH1, hMSH2, hMSH6) and p53 proteins was performed. DNA ploidy (diploid vs
aneuploid/tetraploid) and proliferative indices (PI: S-phase + G(2)M) were
analyzed by flow cytometry. RESULTS: MSI-H was found in 95 (18%) colon cancers.
Proximal tumors (N = 286) were associated with MSI-H, older age (>65 yr), poor
differentiation, and diploid DNA content compared with distal tumors (all P< or =
0.016). Nuclear p53 staining was more frequent in distal tumors (P= 0.002); PI
was unrelated to tumor site. When MSI-H tumors were excluded, no tumor site
related differences were found except for age, which remained associated with
proximal cancers (P= 0.030). Proximal site was associated with improved disease
free survival in all patients (P= 0.042), but not when MSI-H cases were excluded
(P= 0.236). MSI-H status or loss of mismatch repair proteins, diploidy, and lower
PI were associated with improved survival rates. CONCLUSIONS: Tumor site-related
differences in clinicopathological variables, biomarkers, and prognosis of
sporadic colon cancers can be explained by the inclusion of MSI-H cases. Older
age, however, is associated with proximal tumor site independent of MSI status.
PMID- 17026564
TI - Thiopurine methyltransferase (TPMT) activity and adverse effects of azathioprine
in inflammatory bowel disease: long-term follow-up study of 394 patients.
AB - AIM: To prospectively evaluate whether a relationship between thiopurine
methyltransferase (TPMT) activity and incidence of adverse effects (especially
myelotoxicity) exists, in a long-term follow-up study of a large group of
patients with inflammatory bowel disease treated with azathioprine. METHODS: TPMT
activity in red blood cells (RBC) was measured by a radiochemical method in 394
consecutive patients with Crohn's disease (238) or ulcerative colitis (156)
starting treatment with azathioprine. The relationship among several variables
and TPMT values was assessed, and the correlation between such levels and the
incidence of adverse effects was evaluated. RESULTS: Mean TPMT value was 18.6 +/-
4 U/mL RBCs (range 9.4-33.7). No patient had low levels (<5), 7.1% had
intermediate levels (5-13.7), and 92.9% had high levels (>13.8). Differences (P <
0.001) were demonstrated in TPMT activity depending on the type of inflammatory
bowel disease, but not on the remaining variables (including treatment with 5
aminosalycilates). Adverse effects were reported in 74 patients (18.8%), the most
frequent being gastrointestinal intolerance (9.1%) and myelotoxicity (4.3%). No
patient having adverse effects had low TPMT levels. However, mean TPMT activity
was lower in those with adverse effects (16.6 +/- 3 vs 19.1 +/- 4 U/mL, P <
0.001). Moreover, the probability of suffering myelotoxicity in the high TPMT
group was only 3.5%, compared with 14.3% in the TPMT intermediate group (95% CI =
1.37-14.9; OR = 4.5). CONCLUSIONS: The strategy of determining TPMT activity in
all patients prior to initiating treatment with azathioprine could help to
minimize the risk of myelotoxicity, as patients with intermediate TPMT activity
had fourfold more risk than high TPMT activity patients.
PMID- 17026565
TI - Singapore familial adenomatous polyposis (FAP) patients with classical
adenomatous polyposis but undetectable APC mutations have accelerated cancer
progression.
AB - OBJECTIVES: Germline mutation in adenomatous polyposis coli (APC) is detected in
up to 80% of familial adenomatous polyposis (FAP) patients worldwide. In this
study, we evaluated clinical features and APC mutations of Singapore FAP patients
and contrasted genotype-phenotype correlation with Caucasians from other regions
of the world and between FAP patients with and without detectable APC mutations.
METHODS: We screened 242 members from 57 unrelated FAP families using a
combination of cDNA protein truncation test, multiplex ligation-dependent probe
amplification, and differential expression techniques. RESULTS: APC germline
mutations were detected in 50 families. In contrast to Caucasians, fundic gland
polyposis in Singapore patients was associated with APC mutations throughout the
coding region and osteomas were also not confined to codon 767-1573. There was
also no FAP-associated hepatoblastoma or medullablastoma. APC mutation-negative
patients from four families with mixed (adenomatous/hyperplastic/atypical
juvenile) polyps were subsequently reclassified as hereditary mixed polyposis
syndrome (HMPS) patients. APC mutation-negative patients with classical
adenomatous polyposis were negative for MYH, beta-catenin, and Axin 1 mutations.
These patients had a significantly older age at diagnosis (P < 0.001) and more
colorectal cancers (P= 0.017) than patients with APC mutations. CONCLUSIONS: We
achieved a 94% (50/53) APC mutation detection rate via a combination of
techniques, suggesting that the current detection rate is probably not
exhaustive. Singapore patients have some features similar to and other features
distinct from Caucasians. Furthermore, APC mutation-negative patients have
accelerated cancer progression that merits closer surveillance.
PMID- 17026566
TI - Association between liver fibrosis and insulin sensitivity in chronic hepatitis C
patients.
AB - BACKGROUND: Several clinical studies have suggested a possible link between
chronic hepatitis caused by hepatitis C virus (HCV) and the development of
diabetes mellitus. We investigated the association between liver fibrosis and
glucose intolerance in HCV-infected patients by measuring insulin sensitivity and
beta-cell function. METHOD: A total of 83 chronic HCV-infected patients were
recruited into this study. We evaluated insulin sensitivity and beta-cell
function of all patients in a fasting state (homeostasis model assessment of
insulin resistance [HOMA-R] and homeostasis model assessment of beta-cell
function [HOMA-beta]) and after an oral load of 75 g glucose (whole-body insulin
sensitivity index [WBISI] and Delta-insulin/Delta-glucose 30). RESULTS: In a
multivariate analysis, severe fibrosis was the only independent factor associated
with insulin resistance. There were significant differences in both HOMA-R (P=
0.0063) and WBISI (P= 0.0159) between patients with mild fibrosis (N = 34) and
those with severe fibrosis (N = 49). Although HOMA-beta was increased
significantly in the subjects with severe fibrosis compared with those with mild
fibrosis (P= 0.0169), Delta-insulin/Delta-glucose 30 showed no significant
difference in stage of liver fibrosis, suggesting an uncertain association
between liver fibrosis and beta-cell function. CONCLUSION: Our findings suggest
that the development of liver fibrosis is associated with insulin resistance in
HCV-infected patients.
PMID- 17026567
TI - Gut-brain neuropeptides in the regulation of ingestive behaviors and obesity.
AB - The prevalence of obesity has increased to epidemic proportions and has become an
urgent public health problem. Obesity causes significant morbidity and mortality
and its impact on health-care costs in the United States is growing dramatically.
Apart from bariatric surgery treatment, options are limited. Future advances in
treatment will rely on a better understanding of the pathogenesis and physiology
of obesity. Alterations in gastrointestinal (GI) sensory-motor function and
symptoms have been associated with obesity. GI neuroendocrine communications
between the periphery and the brain regulate energy balance and ingestive
behaviors. These interactions are largely mediated by the gut-brain peptides
through negative and positive feedback loops that maintain energy homeostasis.
Bariatric surgery has been shown effective, but the mechanisms of weight loss
following these procedures clearly require further studies and a better
understanding of the affects of bariatric surgery on the gut-brain neuropeptide
homeostasis. Gut-brain peptides may provide attractive therapeutic targets in the
fight against this very morbid disease. We review alterations in GI function and
some of the more important gut-brain neuropeptides that occur in obesity.
PMID- 17026568
TI - Influence of body position and stool characteristics on defecation in humans.
AB - BACKGROUND: Whether defecation is influenced by body position or stool
characteristics is unclear. AIM: We investigated effects of body position,
presence of stool-like sensation, and stool form on defecation patterns and
manometric profiles. METHODS: Rectal and anal pressures were assessed in 25
healthy volunteers during attempted defecation either in the lying or sitting
positions and with balloon-filled or empty rectum. Subjects also expelled a water
filled (50 cc) balloon or silicone-stool (FECOM) either lying or sitting and
rated their stooling sensation. RESULTS: When attempting to defecate in the lying
position, a dyssynergic pattern was seen in 36% of subjects with empty rectum and
24% with distended rectum. When sitting, 20% showed dyssynergia with empty rectum
and 8% with distended rectum. More subjects (p < 0.05) showed dyssynergia in
lying position. When lying, 60% could not expel balloon and 44% FECOM. When
sitting, fewer (p < 0.05) failed to expel balloon (16%) or FECOM (4%). FECOM
expulsion time was quicker (p < 0.02). Stool-like sensation was more commonly (p
< 0.005) evoked by FECOM than balloon. CONCLUSIONS: In the lying position, one
third showed dyssynergia and one-half could not expel artificial stool. Whereas
when sitting with distended rectum, most showed normal defecation pattern and
ability to expel stool. Thus, body position, sensation of stooling and stool
characteristics may each influence defecation. Defecation is best evaluated in
the sitting position with artificial stool.
PMID- 17026569
TI - 30-day mortality after peptic ulcer perforation among users of newer selective
COX-2 inhibitors and traditional NSAIDs: a population-based study.
AB - OBJECTIVES: Nonsteroidal anti-inflammatory drug (NSAID) use is a strong risk
factor for peptic ulcer perforation, yet little is known about the outcome of
this condition among NSAID users. We examined 30-day mortality after peptic ulcer
perforation associated with the use of traditional NSAIDs and newer selective
cyclo-oxygenase-2 (COX-2) inhibitors. METHODS: We conducted a cohort study of
patients with the first hospitalization for peptic ulcer perforation, identified
in discharge registries of three Danish counties between 1991 and 2003. Data on
preadmission NSAID use, other ulcer-related drugs, and comorbidity were likewise
from population-based registries. Mortality was ascertained from the Civil
Registration System. We compared 30-day mortality in NSAID users and nonusers
while adjusting for age, gender, comorbidity, previous uncomplicated peptic
ulcer, and ulcer medication use. RESULTS: Of the 2,061 patients hospitalized with
peptic ulcer perforation, 38% were current NSAID users. The 30-day mortality was
25% overall, and 35% among current NSAID users. Compared with never-use, the
adjusted 30-day mortality rate ratios (MRRs) were 1.8 (95% CI 1.4-2.3) for
current use of NSAIDs alone and 1.6 (95% CI 1.2-2.2) for current use combined
with other ulcer-associated drugs. The mortality increase associated with the use
of COX-2 inhibitors was similar to that of traditional NSAIDs: adjusted MRR for
users of COX-2 inhibitors alone and in combination, 2.0 (1.3-3.1) and 1.4 (0.8
2.5), and for users of traditional NSAIDs alone or in combination, 1.7 (1.3-2.3)
and 1.6 (1.2-2.3). CONCLUSION: Current use of NSAIDs, including COX-2 inhibitors,
is associated with a poor prognosis for patients hospitalized with peptic ulcer
perforation.
PMID- 17026570
TI - Rapid development of diffuse large B-Cell lymphoma after successful eradication
of Helicobacter pylori for gastric MALT lymphoma.
AB - Primary low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the
stomach has a potential to transform to high-grade diffuse large B-cell lymphoma
(DLBCL). However, the clonal relation between MALT lymphoma and de novo DLBCL is
still controversial. We report here three patients with Helicobacter pylori (H.
pylori)-positive gastric MALT lymphoma rapidly progressing to DLBCL at the same
site after successful eradication of H. pylori. Although MALT lymphomas in our
cases did not possess t(11; 18)(q21;q21), sequence analysis of the rearranged
immunoglobulin heavy chain gene showed no clonal relation between preceding MALT
lymphoma cells and de novo DLBCL cells at the same site. These findings question
the scenario of direct clonal progression of low-grade MALT lymphomas without
t(11; 18)(q21;q21) to DLBCL and serve as a reminder of the risk of the
progression of DLBCL with a distinct clonality immediately after H. pylori
eradication for low-grade MALT lymphoma.
PMID- 17026572
TI - Complexity of anti-immunosenescence strategies in humans.
AB - Immunosenescence is characterized by three main aspects: (i) the shrinkage of the
T cell repertoire and the accumulation of oligoclonal expansions (megaclones) of
memory/effector cells directed toward ubiquitary infectious agents; (ii) the
involution of the thymus and the exhaustion of naive T cells; and (iii) a chronic
inflammatory status called inflamm-aging. We present here possible strategies to
counteract these main aspects of immunosenescence in humans with particular
attention to the reduction of antigenic load by pathogens, such as CMV, and the
normalization of intestinal microflora, the possible utilization of IL-7 to
reverse thymic involution, the purging of megaclones, the forced expression of
CD28 on T lymphocytes, the reduction of inflamm-aging and the administration of
nutrients such as vitamin D. Possible drawbacks of all these strategies are
discussed. Finally, the complexity of a rejuvenation approach is stressed, with
particular attention to the inhibitory role played by the "old microenvironment"
on the performance of progenitor cells, the best candidate to counteract the
decline in regenerative potential characteristic of organs and tissues from old
organisms.
PMID- 17026573
TI - Reversibility of the differentiated state: regeneration in amphibians.
AB - In contrast to mammals, some fish and amphibians have retained the ability to
regenerate complex body structures or organs, such as the limb, tail, eye lens,
or even parts of the heart. One major difference in the response to injury is the
appearance of a mesenchymal growth zone or blastema in these regenerative species
instead of the scarring seen in mammals. This blastema is thought to largely
derive from the dedifferentiation of various functional cell types, such as
skeletal muscle, dermis, and cartilage. In the case of multinucleated skeletal
muscle fibers, cell cycle reentry into S-phase as well as fragmentation into
mononucleated progenitors is observed both in vitro and in vivo.
PMID- 17026574
TI - The stairway: a novel behavioral test detecting sensomotoric stroke deficits in
rats.
AB - New therapeutic concepts of cell and tissue replacement therapies have been
introduced in treatment of neurological disorders which require robust and
sensitive sensomotoric behavioral diagnostic test systems for experimental
research. However, most test arrays available are either expensive and/or
sensitive to environmental disturbances. Moreover, an extensive training phase
for experimental animals is often required by conventional tests to get
reproducible data. In this study, we describe a new test array, the Stairway,
that is robust, cost-effective, and needs only a minimum training phase. Its
efficiency is evaluated in comparison to the well-established RotaRod and
modified neurological severity score. Stroke was induced by middle cerebral
artery occlusion. Human umbilical cord blood transplantation (n = 18) was
performed 24 h after stroke by intravenous injection of suspended cells in
comparison to control injections (n = 18), while behavioral assessment was
carried out continuously for 29 days. Furthermore, development of lesions was
monitored by magnetic resonance imaging. The results reveal the Stairway test as
a simple, highly reproducible, and easy manageable test system thus reflecting
therapeutic benefits precisely.
PMID- 17026575
TI - Poly(ether imide) scaffolds as multifunctional materials for potential
applications in regenerative medicine.
AB - This article gives an overview of scaffolds that can be prepared from poly(ether
imide) (PEI). These scaffolds were developed for extracorporeal blood
detoxification processes in which specific compounds from blood or plasma are
removed selectively. Both the preparation of porous microparticles and the
preparation of hollow fibers are described. Commercially available particulate
support materials have the disadvantage of a low accessibility of the internal
pore system, a poor flow-through behavior and low adsorption specificity. Thus,
novel support materials with optimally adapted properties profiles are needed.
The second part of this article shows some recently developed highly asymmetric
PEI hollow fibers. PEI scaffolds can be considered multifunctional because they
combine separation characteristics, biocompatibility, sufficient biostability,
and the possibility of creating tailor-made biofunctional surfaces.
PMID- 17026576
TI - Bone engineering: combining smart biomaterials and the application of stem cells.
AB - Remarkable preclinical progress and achievements in the isolation and
characterization of stem cells from different sources have been made, together
with the ability to control proliferation and differentiation in vitro.
Researchers and physicians pin their hope on stem cells to develop novel
approaches in regenerative medicine. Stem cell therapy is no longer a scientific
discipline in the laboratory or in animal models only, as it is already performed
routinely in the human therapeutical and clinical treatment for hematological
malignancies and clinical trials for bone repair. It has further been recognized
that angiogenesis plays a pivotal role for the successful transplantation of in
vitro engineered tissues like bone structures, for the repair of large bone
defects to facilitate engraftment. We intended to generate transplantable
composite grafts, which consist of in vitro generated bone tissue from
multipotent adult progenitor cells, maintaining an angiogenic potential to ease
and optimize a successful engraftment of long-term sustainable and viable bone
tissue. The other component was generated from several synthetically produced
three-dimensional tissues like fibrin, thrombin, collagen, hydroxyapatite, and
beta-tricalciumphosphate in different compositions and concentrations, all
mimicking natural body structures of bone tissue as biocompatible grafts. We
established an in vitro mouse model, using bone marrow and peripheral blood
derived murine progenitor cells as well as industrially manufactured materials
generating composite grafts. Based on our preliminary results, we propose to
pursue research on composite grafts for an extended graft survival and successful
engraftment of transplanted tissue.
PMID- 17026577
TI - Initiation of mesenchymal condensation in alginate hollow spheres--a useful model
for understanding cartilage repair?
AB - A promising strategy for the regeneration of degenerated cartilage tissue
structure in osteoarthritic joints is the use of mesenchymal precursor cells.
These cells can be triggered to undergo differentiation into functional active
chondrocytes resulting in newly synthesized cartilage. Because chondrogenic
differentiation is initiated by the step of mesenchymal condensation in vitro, it
is of great interest to fully characterize the first lineage specific step in
vitro. Therefore, a modified culture system was developed which mimics the
process in vitro and may finally help to identify the key factors that are
essential for the induction of chondrogenic differentiation in vivo. Compared to
other established 3D culture systems like alginate beads and micromass cultures,
the use of alginate hollow spheres bears the advantage to analyze different
phases of cell aggregation starting from a single cell suspension of previously
isolated and expanded human primary cells of mesenchymal origin.
PMID- 17026578
TI - Electrospinning approaches toward scaffold engineering--a brief overview.
AB - Tissue engineering involves the in vitro seeding of cells onto scaffolds which
assume the role of supporting cell adhesion, migration, proliferation, and
differentiation, and which define the three-dimensional shape of the tissue to be
engineered. Among the various types of scaffold architectures available,
scaffolds based on nanofibers mimicking to a certain extent the structure of the
extracellular matrix offer great advantages. Electrospinning is the technique of
choice for the preparation of such scaffolds. Investigations have revealed that
the nanofibrous structure promotes cell adhesion, proliferation, and
differentiation. Parameters relevant for these processes such as fiber diameters,
surface topology, porosity, mechanical properties, and the fibrous architecture
of the scaffold can be controlled by electrospinning in a broad range.
PMID- 17026579
TI - Membrane bioreactor for cell tissues and organoids.
AB - Progresses in polymeric membrane preparation and in the understanding and control
of their transport properties make possible the design of novel membranes to be
used for cell culture (e.g., hepatocytes, lymphocytes, pancreatic islets) in
biohybrid systems such as therapeutic device or as in vitro model systems for
studying the effects of various drugs and chemicals on cell metabolism. Special
attention is paid to the design of the membrane with defined microstructure and
physicochemical properties as well as to the importance of transport and
physicochemical properties of the membrane in contact with the cells. The
development of new biomaterials and bioreactors able to activate a specific
response of the cells and to maintain cell differentiation for a long time is one
of the most pertinent issues in the field of tissue engineering and regenerative
medicine. Polymeric membranes are attractive for their selectivity and
biostability characteristics in the use of biohybrid systems for cell culture.
Semipermeable membranes act as a support for the adhesion of anchorage-dependent
cells and allow the specific transport of metabolites and nutrients to cells and
the removal of catabolites and specific products. Moreover, new membrane systems
that have been recently realized as the membrane contactors might also
potentially contribute to regenerative medicine and tissue engineering.
PMID- 17026580
TI - A human lymph node in vitro--challenges and progress.
AB - Extracorporeal human lymphatic organs are expected to be excellent tools in the
study of human molecular and cellular bases of the immunologic balance and tissue
harmony. A rational approach and process to design a device and a procedure to
recreate the human lymph node environment in vitro is described with emphasis on
T-cell activation. Based on this approach, a bioreactor and a process supporting
self-assembly of human lymphatic tissues due to proper emulation of human
architecture and homeostasis could be developed.
PMID- 17026581
TI - The cardiovascular tissue-reactor: a novel device for the engineering of heart
valves.
AB - The shortage of human donor valves and disadvantages of current mechanical and
xenogenic valve grafts cause a growing demand for biologically engineered valves.
We developed a bioreactor for in vitro transformation of porcine semilunar heart
valves into human valves. The reactor design was optimized in order to achieve a
complete removal of porcine cells by trypsinization and cellularization of the
remaining matrix with human vascular cells. The physical parameters of the
reactor were characterized. Based on these data, decellularization and
cellularization protocols were developed and the successful application of
protocols was investigated by immunohistochemistry. The resulting reactor
consisted of two connectable and perfuseable modules. Heart valve structures of
varying sizes could be mounted into the reactor and could be completely
depopulated within 4 days by a sequence of enzymatic and mechanical treatments
applied simultaneously to the valves. Complete cellularization with human cells
could be achieved after optimizing the seeding design, density, and time.
PMID- 17026582
TI - Evaluation of liver support systems for preclinical testing by animal trials.
AB - In the present review, various animal models of acute liver failure are reviewed
with respect to their suitability for evaluating liver support systems (LSS)
according to envisaged modes of therapy. In order to increase the value of the
preclinical testing of LSS, it would be advantageous to include more than one
animal model in the evaluation program. It is possible to identify appropriate
sets of models, which make a suitable test system for particular clinical
applications. A standardization of evaluation methods between testing groups
would also be beneficial to the field of liver support.
PMID- 17026583
TI - Visions for regenerative medicine: interface between scientific fact and science
fiction.
AB - This article gives a brief overview of the authors' views on the future
development of tissue engineering with respect to the challenges both to the
materials and life sciences. Emphasis will be placed on the advantages of three
dimensional bioresorbable polymers in combination with relevant molecular cues
and the application of autologous stem or progenitor cells. There is a
requirement for much more diversity in the synthesis of so-called "intelligent"
materials, which respond to external stimuli, as well as the development of novel
drug and gene delivery systems. In addition, much more basic research is
necessary in developmental biology and the application of modern cell and
molecular biology to biomaterial questions.
PMID- 17026584
TI - Future of regenerative medicine: challenges and hurdles.
AB - Tissue regeneration strategies such as tissue engineering, growth factor
administration, and stem cell-based therapies have undergone significant
development over the past two decades. Most notably, we are much closer to
realizing the engineering of whole organs and tissue with complex architecture
than we were 5 years ago. A major driving force has been the demand placed by the
scientific community at large and the public to go beyond simple engineering of
tissues and demonstrate functionality in engineered tissues and functional
recovery upon transplantation. Some recent advances include de novo engineering
of bone, engineering of fully functional bladder, and vascularization of skeletal
muscle constructs. Notwithstanding, several challenges lie ahead in making
regenerative medicine a viable science of the future, the key being the evolution
of programs and policies that promote a close relationship among government
agencies, private sector, and academia, more specifically between materials
scientists, biologists, and clinicians.
PMID- 17026586
TI - The clinical features of anterior prostate cancers.
AB - OBJECTIVE: To identify the clinical characteristics of anterior prostate cancers
(APCs) and to compare these with posterior prostate cancers (PPCs). PATIENTS AND
METHODS: We reviewed 1290 consecutive open and laparoscopic radical
prostatectomies (RPs) at the authors' institution from January 2000 to March
2004. Prostates were processed using a whole-mount technique. Each surgical
specimen was reviewed by one pathologist, and tumour areas were marked, measured
and mapped. Positive surgical margins (PSMs) were defined as the presence of
cancer cells at the inked surface of the specimen. Specimens were then
categorized by the location of their dominant tumour, i.e. pure anterior,
anterior > posterior, posterior > anterior, or pure posterior. We compared the
clinical and pathological characteristics of 259 patients in the pure-anterior
group with the 594 in the pure-posterior group. RESULTS: Before RP, APCs had a
significantly lower biopsy Gleason score (78% vs 68% with Gleason 4-6), fewer
mean biopsy cores positive (2.0 vs 2.6), a smaller median percentage of positive
cores (17% vs 26%), lower clinical stage (T1 in 79% vs 62%), and higher
progression-free probability estimated by preoperative nomogram (86% vs 84%) than
PPCs. Patients with APCs also had more previous negative biopsy sessions. The
pathological analysis of RP specimens showed that those with APCs had higher
tumour volume (1.6 vs 0.83 mL) and had a higher PSM rate (12% vs 7%) than those
with PPCs, despite specimens with PPCs having higher rates of extraprostatic
extension (10% vs 19%). CONCLUSIONS: APCs have lower Gleason grade and lower
rates of extraprostatic extension, yet patients with anterior tumours have higher
overall tumour volumes and higher PSM rates. Because current tools for detecting
and staging prostate cancer can underestimate the extent of anterior prostate
disease, improved methods are needed for localizing and characterizing anterior
cancers.
PMID- 17026587
TI - Sialorphin (the mature peptide product of Vcsa1) relaxes corporal smooth muscle
tissue and increases erectile function in the ageing rat.
AB - OBJECTIVE: To determine if the mature peptide product of the Vcsa1 gene,
sialorphin, could restore erectile function in ageing rats, and whether these
effects are mediated through relaxation of corporal smooth muscle tissue, as we
recently reported that Vcsa1 is one of the most down-regulated genes in the
corpora of rats in three distinct models of erectile dysfunction, and gene
transfer of plasmids expressing Vcsa1 into the corpora of ageing rats restored
erectile function. MATERIALS AND METHODS: Sialorphin was injected
intracorporeally into retired breeder rats, and the effect on the physiology of
corporal tissue was analysed by intracorporal/blood pressure (ICP/BP) measurement
at different times after injection. In organ-bath studies, the ability of
sialorphin (1 microg/mL) to enhance C-type natriuretic peptide (CNP) relaxation
of corporal smooth muscle tissue strips was investigated after pre-contraction
with 1 microm phenylephrine. RESULTS: Intracorporal injection of 100 microg
sialorphin into retired breeder rats resulted in a time-dependent increase in the
ICP/BP response to electrostimulation of the cavernosal nerve. After 55-65 min
the ICP/BP ratio increased to approximately 0.6, a value associated with normal
erectile function. In organ-bath studies after pre-contraction with 1 microm
phenylephrine, 1 microm CNP significantly (67%) increased the relaxation rate of
corporal tissue. This rate of relaxation was increased by 2.5-fold after
incubation with sialorphin (1 microg/mL) compared with carrier alone. CONCLUSION:
These results show that sialorphin has a role in erectile function, probably
through a mechanism that involves relaxation of corporal smooth muscle tissue.
PMID- 17026588
TI - The role of anticholinergics in men with lower urinary tract symptoms suggestive
of benign prostatic hyperplasia: a systematic review and meta-analysis.
AB - OBJECTIVE: To assess the safety and efficacy of anticholinergics in men with
lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia
(BPH) by a systematic review of published reports and a meta-analysis of the
reported outcomes. METHODS: We searched Medline, Embase and Cochrane databases
(1966-2006), and hand-searched relevant reference lists and conference
proceedings, for studies on the use of anticholinergics in men with BPH or
bladder outlet obstruction. Eligible studies were assessed for quality and
foreign language studies were translated. We collected data on all reported
outcomes, conducted meta- analyses on the maximum urinary flow rate (Q(max)),
postvoid residual urine volume (PVR) and volume at first contraction, and
calculated the acute urinary retention (AUR) rate. We used sensitivity analysis
to confirm the findings. RESULTS: We identified five randomized controlled trials
(RCTs) and 15 observational studies. Four RCTs incorporating 633 patients were
included in the meta-analyses. Anticholinergics did not significantly alter
Q(max) (0.1 mL/s, 95% confidence interval, CI, 0.6-0.7). The PVR was increased by
11.6 mL (95% CI 4.5-18.6) although there was no significant difference between
AUR rates. The total International Prostate Symptom Scores (IPSS) were not
significantly different, but there were improvements for IPSS storage subscores
in one RCT. The AUR rate was 0.3% at the 12-week follow-up in 365 men in the RCTs
and observational studies. CONCLUSION: Anticholinergic use in men with LUTS
suggestive of BPH appears to be safe. Further studies are required to establish
efficacy with a suitable precision.
PMID- 17026589
TI - Simultaneous transurethral cystolithotripsy with holmium laser enucleation of the
prostate: a prospective feasibility study and review of literature.
AB - OBJECTIVE: To report experience with holmium laser enucleation of the prostate
(HoLEP) simultaneously with transurethral holmium laser cystolithotripsy (HLC)
for managing bladder outlet obstruction (BOO) and associated vesical calculi; we
also review previously reported cases of managing vesical calculi and associated
BOO. PATIENTS AND METHODS: The high-powered holmium laser is a very efficient
multifunctional endourological instrument that effectively fragments calculi of
all compositions and is capable of haemostatic cutting of tissue, resulting in
minimal bleeding after prostatic resection. A prospective study was conducted
from April 2003 that included 32 men who underwent simultaneous HoLEP with
transurethral HLC at our institution. Demographic, laboratory, peri-operative and
follow-up data were analysed. Complications during and after surgery were
identified to assess the morbidity of procedure. RESULTS: The mean (range) size
of bladder calculi was 34.6 (12-70) mm and the preoperative weight of the
prostate was 51.9 (11-172) g. Combined HoLEP with transurethral HLC was
technically feasible in all patients, and all were stone-free after surgery. The
mean operative duration was 97.7 (40-230) min, the weight of prostate tissue
removed 34.6 (5-88) g, and the duration of catheterization and hospital stay 29.3
h and 34.8 h, respectively. Complications during and after surgery occurred in
12.5% and 15.6% of patients, respectively; all complication were minor and none
caused any residual disability to the patient. No patient required a blood
transfusion or developed clot retention. CONCLUSIONS: Managing bladder stones and
BOO with simultaneous transurethral HLC and HoLEP should be considered the
treatment of choice for such cases. Stones of any size and composition, and
prostates of practically any size can be treated endoscopically using the holmium
laser, with acceptable morbidity once the technique is mastered. The review of
previous reports suggested a need for a prospective study comparing endoscopic
management of BOO and associated bladder stones, with medical management of BOO
and extracorporeal shock wave lithotripsy/endoscopic lithotripsy for bladder
stone.
PMID- 17026590
TI - Ureteric embolization with stainless-steel coils for managing refractory lower
urinary tract fistula: a 12-year experience.
AB - OBJECTIVE: To report our 12-year experience with radiological treatment (ureteric
embolization) for refractory urinary fistula, as malignancy, radiation therapy,
and/or chronic inflammation increase the risk of lower urinary tract fistula
after surgical urinary diversion, which can lead to significant morbidity, and
for patients who are not surgical candidates permanent nephrostomy drainage and
ureteric embolization offer an alternative form of urinary diversion. PATIENTS
AND METHODS: We retrospectively reviewed patients who had ureteric occlusion for
refractory urinary fistula at our institution between 1993 and 2005. Stainless
steel coils, with or without gelatine sponge, were placed antegradely through a
percutaneous nephrostomy tract. Patients were then managed by long-term
nephrostomy drainage until death or definitive reconstructive surgery. RESULTS:
In all, 29 patients (23 women and six men; mean age 59 years, sd 16) were
identified who had urinary fistulae that were refractory to nephrostomy drainage
alone. One patient had a history of severe perineal trauma and the remaining 28
had a history of cancer. Seventeen fistulae occurred in the setting of previous
surgery, 20 patients had received adjunctive pelvic irradiation and 11 had had
chemotherapy. In all, 52 ureters were embolized; occlusion was successful in all
cases, with complete or near-complete (<1 pad/day) dryness within 3 days. No
repeat embolization was required and there were no significant complications. Two
patients were lost to follow-up. Three patients had definitive urinary diversion
surgery and currently are well. One patient is alive and living with nephrostomy
tubes; 23 patients have died. CONCLUSION: Ureteric embolization is a viable
option for managing complex lower urinary tract fistulae in patients with a poor
performance status. It can be used as definitive management in patients with a
limited life-expectancy or as a temporary measure in those for whom another
management plan is anticipated.
PMID- 17026591
TI - The association between T-type Ca2+ current and outward current in isolated human
detrusor cells from stable and overactive bladders.
AB - OBJECTIVE: To determine if bladder overactivity in humans is associated with an
altered activity of Ca(2+) channels in detrusor smooth muscle and the consequent
activation of other ion channels. MATERIAL AND METHODS: Samples of bladder were
obtained from patients with urodynamically stable bladders, or with idiopathic
detrusor overactivity. Isolated cells were patch-clamped with pipettes containing
a Cs(+)-based filling solution to isolate inward currents, or a K(+)-filling
solution to measure outward current. Components of inward current were separated
according to their sensitivity to NiCl(2) (< or =100 microm) and nifedipine.
RESULTS: Ni(2+)-sensitive (T-type) and nifedipine-sensitive (L-type) current was
recorded in all cells. The voltage- and time-dependent properties were similar in
cells from both patient groups. However, the current density of the L-type
current was less, and that of the T-type current was greater, in myocytes from
overactive bladders. In cells from overactive bladders, the mean K(+) current
over the range - 80 to - 50 mV was also higher than in control cells. This
current was sensitive to the large-conductance channel modulator iberiotoxin and
to NiCl(2) (100 microm) CONCLUSIONS: Detrusor myocytes from overactive human
bladders have a higher T-type Ca(2+) current density; we propose that this
increases transient outward currents, and so might contribute to higher levels of
spontaneous activity.
PMID- 17026592
TI - The value of frozen-section analysis of ureteric margins on surgical decision
making in patients undergoing radical cystectomy for bladder cancer.
AB - OBJECTIVE: To prospectively investigate the value of routine frozen-section
analysis (FSA) of the ureteric margin for detecting distal ureteric malignancy in
patients undergoing cystectomy for bladder transitional cell carcinoma (TCC).
PATIENTS AND METHODS: In all, 100 consecutive patients had a radical cystectomy
for TCC of the bladder; routine FS biopsies were obtained from the lower ureters
of all. Definitive pathology with step-sectioning of the lower ureters was
reviewed, and the results of paraffin-wax embedded sections and FSA were
compared. The true incidence of distal ureteric malignancy was identified and
correlated with different clinical and pathological variables. RESULTS: There
were 193 ureteric specimens examined; 16 ureters (8.3%) in 14 patients showed
evidence of malignancy by FSA. True distal ureteric malignancy was diagnosed in
29 ureteric specimens (15%) in 24 patients. The sensitivity and specificity of
the FSA were 45% and 98%, respectively, while the positive and negative
predictive values were 81% and 91%, respectively. There was no significant
correlation between distal ureteric malignancy and: patient age, tumour site or
morphology, clinical or pathological staging, ipsilateral hydronephrosis,
suspicious intraoperative ureter, biopsy or tumour grade, associated carcinoma in
situ or nodal involvement. Male gender and positive intraoperative FSA were the
only predictors significantly associated with distal ureteric malignancy by
univariate analysis (P = 0.01 and <0.01, respectively). Both predictors remained
significant on multivariate analysis. CONCLUSION: A positive ureteric FSA during
cystectomy has a high predictive value in the diagnosis of distal ureteric
malignancy, and is justified as an independent predictor in male patients with
bladder TCC.
PMID- 17026593
TI - The effects of a new selective beta3-adrenoceptor agonist (GW427353) on
spontaneous activity and detrusor relaxation in human bladder.
AB - OBJECTIVE: To examine the effects of a new selective beta3-adrenoceptor agonist,
GW427353 on human detrusor function, as beta2- and beta3-adrenoceptors have been
identified in the bladder, and can mediate detrusor relaxation, but beta3
adrenoceptors are less widely distributed and beta3-adrenoceptor agonists should
have the therapeutic advantage of producing fewer treatment side-effects.
PATIENTS AND METHODS: 'Normal' human detrusor was retrieved from 12 patients
(mean age 56 years) at cystectomy and from organ donors. Detrusor strips (4 x 1 x
1 mm) were mounted in superfused organ baths. Tone was induced with carbachol (5
x 10(-7)m) before applying either a nonselective beta-adrenoceptor agonist
(isoprenaline) or GW427353 (with or without the beta3-adrenoceptor antagonist,
SR59230A). In addition, the effect of GW427353 was tested on intrinsic nerve
evoked smooth muscle contraction over time. Effects on spontaneous activity were
also recorded. RESULTS: GW427353 produced significant relaxation at
concentrations of >10(-7)m; isoprenaline produced a significant effect from 10(
6)m, but otherwise both agonists had similar effects. The addition of SR59230A
(10(-7)m), produced partial inhibition of the GW427353 response. GW427353 at 10(
6)m significantly reduced spontaneous activity within 10 min of incubation, and
at higher concentrations (>5 x 10(-6)m) inhibited detrusor contractions evoked by
electrical field stimulation. CONCLUSION: Neuropathic bladder dysfunction is
characterized by increased spontaneous activity and involuntary detrusor
contractions, which can result in urinary frequency, urgency, nocturia and
incontinence. The novel feature of GW427353 is the ability to suppress
spontaneous activity and produce significant relaxation in human detrusor tissue
at low concentrations, whilst also inhibiting evoked detrusor contractions at
higher concentrations.
PMID- 17026594
TI - A clinical assessment of the performance of a sensor to detect crystalline
biofilm formation on indwelling bladder catheters.
AB - OBJECTIVES: To test the ability of a sensor developed to signal infection by the
organisms that generate the crystalline biofilms that encrust catheters, to give
an early warning that encrustation was occurring on patients' catheters, as the
care of many patients undergoing long-term bladder catheterization is complicated
by the encrustation and blockage of their catheters. PATIENTS AND METHODS: Twenty
patients were followed prospectively for the lifetime of one of their catheters.
Sensors based on cellulose acetate/bromothymol blue were placed in the urine
collection bags, which were changed as usual at weekly intervals. The
bacteriology was assessed and pH determined weekly on urine samples. Photographic
records were made of the sensors twice weekly. On removal, each catheter was
examined for encrustation and blockage. RESULTS: Proteus mirabilis was not
isolated from five patients and in these cases the sensor colour remained golden
yellow to brown. The catheters drained for the scheduled period and showed no
signs of encrustation. By contrast, the sensors turned dark blue/black in the
urine of all 15 patients infected with P. mirabilis. All these patients'
catheters were encrusted and in 12 the catheters blocked. The mean interval
between the sensor signalling and the catheter blocking was 12 days. CONCLUSION:
The cellulose acetate/bromothymol blue sensors placed in the urine collection
bags are capable of signalling infection by P. mirabilis. They also signal the
early stages of catheter encrustation and allow catheter replacement in ample
time to avoid the clinical crises and emergency referrals caused by catheter
blockage.
PMID- 17026595
TI - Clinically significant prostate cancer found incidentally in radical
cystoprostatectomy specimens.
AB - OBJECTIVE: To review the incidence, histopathological features and clinical
outcomes of patients with incidental prostate cancer found in radical
cystoprostatectomy (RCP) specimens excised for bladder cancer, to determine if
these cancers affected the follow-up strategy and if prostate-sparing cystectomy
would be appropriate for these patients. PATIENTS AND METHODS: We retrospectively
reviewed the charts of men who had a RCP for transitional cell carcinoma (TCC) of
the bladder, at our institution between 1987 and 2003. Patients with a
preoperative diagnosis or clinical suspicion of prostate cancer were excluded
from further analysis. We identified those men with incidental prostate cancer in
the RCP specimens. The patients' demographic, histopathological and clinical
outcome data were collected. RESULTS: In all, 217 men had RCP for TCC between
1987 and 2003; 13 were excluded from the study due to a preoperative diagnosis or
clinical suspicion of prostate cancer, and 58 (28%) were found to have incidental
prostate cancer. The mean (range) follow-up was 47 (6-157) months. Of these
prostate cancers, 20% were of Gleason score > or = 7 and two patients developed
local and metastatic prostate cancer recurrences. CONCLUSION: Incidental prostate
cancer is a relatively common finding in RCP specimens, with a significant
proportion having the characteristics of clinically relevant prostate cancer. The
follow-up for prostate cancer should be incorporated with that for TCC and
adapted according to the grade and stage of the prostate cancer. Preserving the
prostate in an attempt to decrease the morbidity after RCP carries a high risk of
significant prostate cancer in the residual prostatic tissue, suggesting that
prostate-sparing cystectomy should only be reserved for a highly selected group
of patients.
PMID- 17026596
TI - Retroperitoneal anomalies in men with testicular germ cell tumours.
AB - OBJECTIVES: To assess whether vascular and other retroperitoneal anomalies are
more frequent during retroperitoneal lymph node dissection (RPLND) for metastatic
testicular tumours (when retroperitoneal masses persist after chemotherapy) than
would be expected, based on the initial observations from one centre with a large
experience of RPLND in the UK. PATIENTS AND METHODS: A prospective series of 278
consecutive patients treated with RPLND for testicular tumours comprised the
sample population. For each patient the presence or absence of four factors from
the history was recorded. Each patient then underwent RPLND. During surgery, a
template was constructed of the anatomy of the retroperitoneum and the
information stored. Eight different retroperitoneal anatomical anomalies were
identified in the sample population; the incidence of each was then compared with
the largest available study of a normal population, and differences analysed
statistically. RESULTS: Of the 278 patients who had RPLND, 55 had 59 anomalies
(21%), found by history and as retroperitoneal vascular and urological anomalies;
cryptorchidism was present in 7.6%, 9.5 times the incidence in the control
population (P < 0.01). A left-sided inferior vena cava was present in 3.6% of
patients, 21 times the incidence in the control population (P < 0.001); a retro
aortic left renal vein in 3.2%, four times that in the control population (P <
0.05); and ipsilateral renal agenesis had an incidence of 1% in the test
population, 11 times greater than in the control population (P < 0.01).
CONCLUSIONS: This prospective study of 278 RPLNDs provides evidence that some
retroperitoneal anatomical anomalies are associated with testicular germ cell
tumours. The link between maldescent and testicular tumours, rather than an
isolated association, should be considered as part of a spectrum of
retroperitoneal anomalies that occur in these men.
PMID- 17026597
TI - The prevalence and predictors of erectile dysfunction in men with newly diagnosed
with type 2 diabetes mellitus.
AB - OBJECTIVE: To determine the prevalence of and risk factors for erectile
dysfunction (ED) in men newly diagnosed with type 2 diabetes mellitus (DM).
PATIENTS AND METHODS: All consecutive samples of men newly diagnosed with type 2
DM attending the diabetes centre in the capital of Kuwait were included in the
study. Face-to-face interviews with the men were conducted using the
International Index of Erectile Function (IIEF)-5 questionnaire. A threshold IIEF
5 score of <21 was used to identify men with ED. Pertinent clinical and
laboratory characteristics were collected. RESULTS: Of 323 men with newly
diagnosed type 2 DM, 31% had ED; comparing potent men and men with ED, there were
statistically significant differences for smoking, duration of smoking,
hypertension, education level, body mass index and serum glycosylated haemoglobin
level. Among these, age was the most important risk factor identified by
multivariate logistic regression. CONCLUSION: About a third of men with newly
diagnosed type 2 DM had ED; this was associated with many variables, but most
notably with age at presentation.
PMID- 17026598
TI - Testicular microlithiasis: what does it mean clinically?
AB - OBJECTIVE: To review our current practice of follow-up for boys with testicular
microlithiasis (TM), an uncommon condition characterized by calcification within
the seminiferous tubules, detected by ultrasonography (US); TM has been
associated with both benign and malignant conditions of the testes but the
natural history of TM in children remains unclear. PATIENTS AND METHODS: All boys
diagnosed with TM over a 14-year period were included in this study. A search of
the radiology database was carried out using the keywords 'testicular
microlithiasis' and 'testicular calcification'. A retrospective case-note review
was then used to determine age at diagnosis, presenting symptoms, indication for
testicular US, outcome and follow-up. We also searched Medline/PubMed, using the
same keywords for published data on TM from 1970 to 2006. RESULTS: Over the study
period 711 testicular scans were taken in 623 patients; seven cases (1.1%) of TM
were identified. The mean (range) age at presentation was 12 (7-15) years. The
presenting symptoms were testicular pain (three), undescended testes (two),
hydrocele (one) and asymptomatic scrotal swelling (one). In five cases the TM was
bilateral and in two a solitary kidney was identified. Only one patient had
tumour markers measured (beta-human chorionic gonadotrophin and alpha
fetoprotein) and these were within normal limits. On yearly US follow-up, the TM
was less prominent in one patient, unchanged in four and two were lost to follow
up. Three patients are currently on yearly US follow-up while two are under the
care of adult general surgeons. The analysis of reports published to date
indicated that malignancy only develops when TM is associated with other
predisposing factors. CONCLUSION: There is no convincing evidence that TM alone
is premalignant. However, when it accompanies other potentially premalignant
features we recommend annual US follow-up.
PMID- 17026599
TI - Clinicians' attitudes to prostate cancer peer-support groups.
AB - OBJECTIVE: To assess clinicians' knowledge and attitudes to prostate cancer peer
support groups, essential in improving support services for men with prostate
cancer, as patients' perceptions of their clinicians' attitudes to such groups
predict patients' positive and negative perceptions of their experiences at such
groups. SUBJECTS AND METHODS: In all, 36 clinicians (75% response) across
Australia, of whom 27 were urologists and nine were radiation oncologists, were
interviewed in-depth using a key-informant approach. Nine clinicians were from
regional Australia, with the remaining 27 from major metropolitan settings.
Subsequently, 30 clinicians (69% response) completed surveys to confirm
identified themes. RESULTS: Peer support was rated positively by most clinicians
and most report a fair to good knowledge of such groups. However, less than a
quarter regularly refer their patients to these groups. While clinicians can
describe positive aspects of peer support, many are concerned that biased
viewpoints and misinformation within these groups might potentially contribute to
patients' decisional uncertainty and regret. CONCLUSIONS: Further research is
needed to establish for whom these support groups are most helpful. Concerns
about misleading information that might be proffered in support groups is a
barrier to clinician referral to these groups. Dialogue between prostate cancer
interest groups and clinicians to resolve concerns presents as a key strategy to
improve support for men with prostate cancer.
PMID- 17026600
TI - A dynamic journal for a dynamic profession.
PMID- 17026601
TI - The path to modern industrial colour measurement.
PMID- 17026602
TI - From lower to higher colour metrics: a historical account.
AB - BACKGROUND: 'Lower colour metrics' describes the laws of colour mixture as
manifest in trichromatic colour space and best known in its two-dimensional
projection, the chromaticity diagram. 'Higher colour metrics' describes how
distance in this colour space translates into perceptual difference. It is higher
in the sense that it builds on the fundamentals of lower colour metrics. METHODS:
A historical account is given of the development of higher colour metrics, with
many ups and downs, since Helmholtz started it at the end of the 19th Century.
RESULTS: Despite long periods of silence, Helmholtz's basic ideas have survived
by successfully extended modelling, which could also account for seemingly
paradoxical effects of luminance and saturation on colour discrimination.
CONCLUSION: The subject theme, which presently is at a low tide of interest,
deserves the renewed interest of colour vision researchers.
PMID- 17026603
TI - Sarcoidosis: case report and review.
AB - Sarcoidosis is a granulomatous disorder of uncertain aetiology that can affect
almost any organ. Anterior uveitis is a feature of the condition in about 30 per
cent of those affected. We describe a patient with sarcoidosis presenting with
anterior uveitis and describe a diagnostic approach. Sarcoidosis is a condition
that must be considered in patients presenting with symptomatic uveitis, as the
underlying disease is serious and usually treatable. The diagnosis of sarcoidosis
is aided by an understanding of the pattern of organ involvement and may
ultimately require tissue confirmation through biopsy of granulomata, including
those found in the ocular adnexa.
PMID- 17026604
TI - Monocular and binocular thresholds for abruptly and gradually presented illusory
contours.
AB - BACKGROUND: In this study, monocular thresholds and binocular summation for
abrupt onset/offset versus gradually revealed phantom letter E (illusory
contours) stimuli are compared to determine the suitability of these stimuli for
assessment of the integrity of two of the major retinal streams: the
magnocellular and the parvocellular pathways. Such tests are important in
progressive retinal disease where disease severity may differ between the classes
of retinal ganglion cells and between the two eyes. Abrupt onset phantom contours
have long been considered to activate the magnocellular visual pathway and we
propose that gradually revealed high contrast ramped onset/offset stimuli are
more likely to promote the more sustained processing of the parvocellular stream.
METHODS: Contrast discrimination thresholds for monocular and binocular viewing
were compared in a counter-balanced order in 70 young normal subjects, using
tests of contrast threshold for a flicker-defined letter E produced by
alternation of light and dark dots. Three onset/offset conditions were used -
abrupt onset that was maintained for 34 milliseconds (four frames of 8.5
milliseconds) then discontinued, ramped onset over 34 milliseconds (four frames)
with offset over 34 milliseconds and ramped onset over 85 milliseconds (10
frames) with offset over 85 milliseconds. RESULTS: Contrast thresholds for
identification of the orientation of the E, when presented with four frames
ramped onset and offset when compared to the four frames abrupt onset/offset were
three times higher, irrespective of monocular or binocular viewing conditions.
Threshold contrasts were seven times higher when the 10 frames ramped
onset/offset stimuli were compared to abrupt four frames onset/offset. Binocular
contrast thresholds were reduced by approximately 40 per cent compared to
monocular thresholds for all conditions. The binocular increase in contrast
sensitivity is approximately equal for abrupt transiently presented stimuli and
for gradually presented more sustained stimuli. DISCUSSION: The results indicate
that the same mechanisms of monocular processing and binocular summation are used
for identification of a flickering contrast-defined phantom contour under
presentation conditions, which are characteristic of the temporal and contrast
preferences of the primate magnocellular and parvocellular visual pathways. This
suggests that the phantom contour E test may be useful for clinical
differentiation of the integrity of the M and P retinal ganglion-derived visual
pathways, regardless of whether it is applied monocularly or binocularly.
PMID- 17026605
TI - A novel method to measure oxygen permeability and transmissibility of contact
lenses.
AB - PURPOSE: The present paper describes an accurate and cost-effective method
requiring simple equipment to measure the oxygen permeability and
transmissibility of contact lenses. METHOD: The method involves accurate
measurement of oxygen across the material by allowing the gas (oxygen) to pass
through the lens material in a specially fabricated lens mould. The expelled gas
is collected by dissolution in ethanol and the oxygen is measured by titration of
the solvent. RESULT: This method is suitable for the measurement of oxygen
permeability and transmissibility of contact lenses of varying thickness and
different radii of curvature. It can measure Dk and Dk/t of collagen bandage
lenses in both wet and dry conditions. CONCLUSION: The oxygen permeability and
transmissibility values obtained by this method were compared with the oxygen
permeability standard values of commercially available contact lenses and the
results are summarised.
PMID- 17026606
TI - Effect of Proview self-tonometry on pharmaceutical compliance.
AB - AIM: To evaluate changes in patient compliance with medical treatment while using
the Proview Eye Pressure Monitor. METHODS: A crossover study design was used to
compare the compliance of patients with established use of topical medication to
lower intraocular pressure in the treatment of primary open-angle glaucoma.
Thirty-two patients currently managed with latanoprost 0.005%, brimonidine 0.15%,
travoprost 0.004% or bimatoprost 0.03% as monotherapy or in combination were
randomly assigned to two study groups. Group 1 was instructed in the use of
Proview Eye Pressure Monitor three times daily for 30 days as an adjunct to the
glaucoma regimen. Group 2 was observed with no change in the patients' treatment
regimen during this phase of study. A crossover occurred at 30 days. Compliance
was monitored by assigning new bottles of topical medication during each phase of
study. Bottles were weighed with a Mettler balance (Mettler Toledo Co.) at the
initiation and completion of each phase. The changes in bottle-weight determined
the amount of medication consumed by each patient for each phase of the study.
The weights were analysed to estimate changes in compliance. RESULTS: A paired
samples Student t-test compared the consumed bottle weights with and without
Proview Eye Pressure Monitor usage. No statistical significance or trend was
identifiable (p = 0.98). Use of the Proview Eye Pressure Monitor did not
significantly change compliance with adjunct eye drop medication. CONCLUSION: The
use of the Proview Eye Pressure Monitor use did not improve but appeared to
hinder compliance with glaucoma treatment in this study.
PMID- 17026607
TI - Delayed surface opacification of a hydroview intraocular lens.
AB - The insertion of an intraocular lens during cataract surgery is routine but
delayed opacification of hydrophilic foldable intraocular lenses (IOLs) has been
increasingly noticed as a late post-operative complication. Such opacification
may present with reduced visual acuity and can be diagnosed with slitlamp
biomicroscopy. Lens explantation may be required. We report an 89-year-old female
presenting with opacification of a Hydroview IOL and correlate the clinical
findings of the lens in situ with the light microscopy of the explanted lens, as
well as transmission electron microscopy (TEM), scanning electron microscopy
(SEM) and elemental analysis. Pathological analysis of an explanted IOL may
assist in a better understanding of the condition and may become relevant in
medico-legal proceedings.
PMID- 17026608
TI - Ocular manifestations of molluscum contagiosum.
AB - PURPOSE: Two cases of molluscum contagiosum (MC) are presented to illustrate the
range of potential anterior segment complications of this condition. METHODS:
Clinical records for two patients diagnosed with MC are retrospectively reviewed.
Diagnosis and management of both cases are presented. RESULTS: The first patient
demonstrates a classic presentation of ocular MC. The patient was young and had
several dermal lid lesions at the time of presentation. The second case
represents a less common presentation. The patient was an adult and had a single
lid lesion that was not apparent at the initial examination. Both patients had
follicular conjunctivitis that resolved with excision of the concomitant eyelid
lesions. CONCLUSION: MC is a treatable cause of chronic conjunctivitis or
keratoconjunctivitis. Eye-care providers should be mindful that MC could present
as a follicular keratoconjunctivitis with or without obvious dermal lid lesions.
The possibility of immuno-compromise must be considered in patients with multiple
large lesions, cutaneous lesions that do not respond to standard therapy, or
recurrent lesions.
PMID- 17026609
TI - ACGIH defends its guidelines for protection against retinal damage by optical
radiation.
PMID- 17026611
TI - Ocular therapeutics.
PMID- 17026615
TI - Chimera and other fertilization errors.
AB - The finding of a mixture of 46,XX and 46,XY cells in an individual has been
rarely reported in literature. It usually results in individuals with ambiguous
genitalia. Approximately 10% of true human hermaphrodites show this type of
karyotype. However, the underlying mechanisms are poorly understood. It may be
the result of mosaicism or chimerism. By definition, a chimera is produced by the
fusion of two different zygotes in a single embryo, while a mosaic contains
genetically different cells issued from a single zygote. Several mechanisms are
involved in the production of chimera. Stricto sensu, chimerism occurs from the
post-zygotic fusion of two distinct embryos leading to a tetragametic chimera. In
addition, there are other entities, which are also referred to as chimera:
parthenogenetic chimera and chimera resulting from fertilization of the second
polar body. Furthermore, a particular type of chimera called 'androgenetic
chimera' recently described in fetuses with placental mesenchymal dysplasia and
in rare patients with Beckwith-Wiedemann syndrome is discussed. Strategies to
study mechanisms leading to the production of chimera and mosaics are also
proposed.
PMID- 17026616
TI - Presymptomatic and predictive genetic testing in minors: a systematic review of
guidelines and position papers.
AB - The objective of this study is to review ethical and clinical guidelines and
position papers concerning the presymptomatic and predictive genetic testing of
minors. The databases Medline, Philosopher's Index, Biological Abstracts, Web of
Science and Google Scholar were searched using keywords relating to the
presymptomatic and predictive testing of children. We also searched the websites
of the national bioethics committees indexed on the websites of World Health
Organization (WHO) and the German Reference Centre for Ethics in the Life
Sciences, the websites of the Human Genetics Societies of various nations indexed
on the website of the International Federation of Human Genetics Societies and
related links and the national medical associations indexed on the website of the
World Medical Association. We retrieved 27 different papers dealing with
guidelines or position papers that fulfilled our search criteria. They
encompassed the period 1991-2005 and originated from 31 different organizations.
The main justification for presymptomatic and predictive genetic testing was the
direct benefit to the minor through either medical intervention or preventive
measures. If there were no urgent medical reasons, all guidelines recommend
postponing testing until the child could consent to testing as a competent
adolescent or as an adult. Ambiguity existed for childhood-onset disorders for
which preventive or therapeutic measures are not available and for the timing of
testing for childhood-onset disorders. Although the guidelines covering
presymptomatic and predictive genetic testing of minors agree strongly that
medical benefit is the main justification for testing, a lack of consensus
remains in the case of childhood-onset disorders for which preventive or
therapeutic measures are not available.
PMID- 17026620
TI - Inherited association of breast and colorectal cancer: limited role of CHEK2
compared with high-penetrance genes.
AB - We assessed the association between breast cancer (BC) and colorectal cancer
(CRC) from referral pattern to the Regional Genetics Service including molecular
analysis. Hospital computer records and/or department referral books were used to
identify cases referred to the Regional Genetic Service during a 16-year period
(1990-2005 inclusive). All files were reviewed along with associated demographic
data, risk assessments, referral details and results from mutation testing.
Families were assessed for hereditary breast and colorectal cancer (HBCC)
criteria, and all families with eligible individuals were tested for the 1100delC
mutation in CHEK2. A total of 8,612 families were identified. One hundred and
sixteen of 1,631 (7.5%) families with a primary referral for CRC fulfilled the
criteria for HBCC, whereas only 68/6981 (1%) BC referrals fulfilled these
criteria. Blood samples were obtained from 113 individuals from 83/184 families.
Only 1/113 (1%) has screened positive for the CHEK2 mutation, whereas 14 (17%)
families segregate BRCA1/2 mutations and at least 7 (8.5%) carry MLH1/MSH2
mutations. HBCC syndrome, if it exists as a separate entity, is not likely to be
due to CHEK2 mutations. Many families are explicable by existing high-penetrance
genes, and further work is necessary to elucidate whether the remainder is due to
chance or as yet undiscovered genes.
PMID- 17026621
TI - Maturity of judgement in decision making for predictive testing for nontreatable
adult-onset neurogenetic conditions: a case against predictive testing of minors.
AB - International guidelines developed to minimize harm from predictive testing for
adult-onset, nontreatable neurogenetic conditions such as Huntington disease (HD)
state that such testing should not be available to minors. Some authors have
proposed that predictive testing for these conditions should be available to
minors at the request of parents and/or of younger adolescents themselves. They
highlight the lack of empirical evidence that predictive testing of minors causes
harm and suggest that refusing to test minors may be detrimental. The current
study focuses on the context of predictive test requests by adolescents younger
than 18 years, and presents arguments and evidence that the risk of potential
harm from testing such young people is sufficiently high to justify continued
caution in this area. A study based on a model of psychosocial maturity found
that the 3 factors involved in maturity of judgement in decision making -
responsibility, temperance and perspective - continue to develop into late
adolescence. There is also evidence that the prefrontal areas of the brain, which
are involved in executive functions such as decision making, are not fully
developed until early adulthood. Combined with evidence of adverse long-term
effects, from research with adults who have undergone predictive testing, these
findings constitute grounds for retaining a minimum age of 18 years for
predictive testing for nontreatable conditions. Further research on assessment of
maturity will assist with reaching a consensus on this issue.
PMID- 17026622
TI - Association of the CT gene (CA) polymorphism with BMD in osteoporotic Mexican
women.
AB - Calcitonin (CT) plays a role in the pathogenesis of osteoporosis and genetic
variations in or adjacent to the CT gene may be associated with loss of bone
mineral density (BMD). The correlation between a dinucleotide (cytosine-adenine)
repeat polymorphism at the CT locus and BMD was examined in 70 osteoporotic
women, 70 non-osteoporotic women and 500 subjects from the Mexican population.
The allele A and genotype AA frequencies were significantly higher in
osteoporotic women than in non-osteoporotic women (60% vs 32%; p < 0.0001 and 41%
vs 14%; p = 0.0007, respectively). Genotype AA was associated with the presence
of osteoporosis [odds ratio 2.58; 95% confidence interval (CI); 1.62-4.12].
Likewise, the loss of lumbar BMD and T scores were related to the presence of
allele A: subjects with a single A allele displayed lower values for lumbar BMD
and T score (84.02% and -1.51, respectively) than those who do not present any A
allele (89.61% and -0.88, respectively). Individuals with two alleles A showed
the lowest lumbar BMD and T-score values (73.77% and -2.51, respectively).
Analysis of potential confounder demonstrated that aging has a significant effect
on osteoporosis development (odds ratio 1.1; 95% CI; 1.1052-1.152).
PMID- 17026623
TI - An updated mutation spectrum in an Australian series of PJS patients provides
further evidence for only one gene locus.
AB - The genetic predisposition Peutz-Jeghers Syndrome (PJS) has been shown to be
associated with mutations in the serine threonine kinase 11 (STK11) gene but only
a proportion of probands have been shown to harbour changes in the gene. The
remaining patients were proposed to be either associated with a second PJS gene
or they harboured more cryptic mutations within the STK11 gene itself. With the
introduction of the multiplex ligation probe amplification (MLPA) assay, large
sequence losses or gains can be more readily identified. In this report we have
screened 33 PJS patients from unrelated families, employing a combination of
denaturing high-performance liquid chromatography, direct DNA sequencing and the
MLPA assay to identify deleterious changes in the STK11 gene. The results
revealed that 24 (73%) of patients diagnosed with PJS-harboured pathogenic
mutations in the STK11 gene, including 10 (36%) with exonic or whole-gene
deletions. No phenotypic differences were identified in patients harbouring large
deletions in the STK11 gene compared to patients harbouring missense or nonsense
mutations. Mutation analysis in PJS should include techniques such as MLPA to
identify large exonic or whole-gene deletions and rearrangements. The high
proportion of families with identifiable mutations in the STK11 gene using this
range of techniques suggests that most, if not all PJS, is attributable to
mutations in the STK11 gene, perhaps including as yet undiscovered changes in
promoter or enhancer sequences or other cryptic changes.
PMID- 17026624
TI - Origin of the SCA7 gene mutation in South Africa: implications for molecular
diagnostics.
PMID- 17026625
TI - Large deletions of the MECP2 gene in Chinese patients with classical Rett
syndrome.
PMID- 17026626
TI - A novel mutation in BAP/SIL1 gene causes Marinesco-Sjogren syndrome in an
extended pedigree.
PMID- 17026627
TI - Introduction: genetic diversity and science communication.
PMID- 17026628
TI - The post-Human Genome Project mindset: race, reliability, and health care.
AB - The following essay reports on the first session of a 2-day workshop on genetic
diversity and science communication, organized by the Institute of Genetics. I
argue that the four talks in this session reflected two different facets of a
'post-Human Genome Project (HGP)' view of human genetics. The first is
characterized by an increasing interest in genetic differences. Two speakers -
Troy Duster and Jasber Singh - expressed skepticism about one aspect of this
trend: an emphasis on race in medicine and genetics. The other two speakers -
Kenneth Weiss and Gustavo Turecki - spoke to a second facet of the post-HGP view:
a recognition of the difficulty in translating genetic discovery into medical or
public health applications. Though both sets of talks were highly critical of
current trends in genetic research, they pulled in opposite directions: one
warned about the role of genetics in stabilizing racial categories, while the
other lamented the failure of any genetic claims or categories to stabilize at
all. I argue that the use of racial categories in medicine seems likely to
encounter scientific, medical, and social challenges.
PMID- 17026629
TI - The challenges of translating genomic knowledge.
AB - Knowledge translation has been described as 'the exchange, synthesis and
ethically-sound application of research findings within a complex set of
interactions among researchers and knowledge users'. While the objectives of
knowledge translation have been geared to accelerating the transfer of knowledge
from producers to users, this essay argues that translation processes are seldom
linear and are much more complex. Using the examples of how scientific
institutions and the media communicate with various publics and how publics
respond to or make use of genomic and genetic information presented at the
workshop, this report suggests that the complexities of translation - who does
it, how, using what assumptions, towards what ends, need to be examined and
better understood.
PMID- 17026630
TI - Assessing risk assessment: genetic testing and screening for complex disease.
AB - This paper reports on the presentations from the second session of a 2-day
workshop on genetic diversity and science communication, organized by the
Institute of Genetics. The four talks in this session (by Sarah Cunningham
Burley, Gail Geller, Michael Hayden, and Theresa Marteau) focused on the topic of
risk assessment in the context of genetic testing, screening and preventive
medicine for complex disease. Each talk underscored the urgency and importance of
evaluating when and for whom risk assessment may be useful. A recurrent theme was
the need to attend closely to the diverse ways that risk is constructed,
perceived and communicated in a variety of contexts and the significant
implications of this for laypersons as well as experts. Although there was no
consensus on when genetic risk assessment ceases (or might begin) to be useful,
ensuing dialogue between presenters and participants reflected what is perhaps a
new and critical engagement with how risk assessment itself is assessed. In
response to this impetus, I use the word RISK as a heuristic to identify, extract
and amplify four tendencies that appear to advance understandings of risk
assessment towards a more explicitly reflexive, interpretive, and situated form
of knowing.
PMID- 17026631
TI - Science communication in transition: genomics hype, public engagement, education
and commercialization pressures.
AB - This essay reports on the final session of a 2-day workshop entitled 'Genetic
Diversity and Science Communication', hosted by the CIHR Institute of Genetics in
Toronto, April 2006. The first speaker, Timothy Caulfield, introduced the
intersecting communities that promulgate a 'cycle of hype' of the timelines and
expected outcomes of the Human Genome Project (HGP): scientists, the media and
the public. Other actors also contribute to the overall hype, the social science
and humanities communities, industry and politicians. There currently appears to
be an abatement of the overblown rhetoric of the HGP. As pointed out by the
second speaker, Sharon Kardia, there is broad recognition that most phenotypic
traits, including disease susceptibility are multi-factorial. That said, George
Davey-Smith reminded us that some direct genotype-phenotype associations may be
useful for public health issues. The Mendelian randomization approach hopes to
revitalize the discipline of epidemiology by strengthening causal influences
about environmentally modifiable risk factors. A more realistic informational
environment paves the way for greater public engagement in science policy. Two
such initiatives were presented by Kardia and Jason Robert, and Peter Finegold
emphasized that science education and professional development for science
teachers are important components of later public engagement in science issues.
However, pressures on public research institutions to commercialize and seek
industry funding may have negative impacts in both encouraging scientists to
inappropriately hype research and on diminishing public trust in the scientific
enterprise. The latter may have a significant effect on public engagement
processes, such as those proposed by Robert and Kardia.
PMID- 17026632
TI - Conclusion: genetic diversity and science communication - some issues of
'translation' and language.
AB - This commentary concerns some key themes from the symposium. While molecular
genetics may provide new opportunities to articulate biological concepts of race,
the ideological baggage associated with the term suggests that it is best dropped
from discussions. In screening programmes and genetic practice, ethnic identity
is likely to be an uncertain surrogate to identify individuals with particular
genetic variants. Precise language and explanation will aid communication about
genetic matters. Talking of genes for particular traits or diseases is unhelpful.
School teaching of classic Mendelian genetics is ineffective and should be
replaced with some teaching of elementary developmental biology based on matters
of everyday salience and interest. Social science literature is replete with
unfounded claims of geneticization.
PMID- 17026635
TI - Is overweight based on BMI a good predictor of risk for hypertension among
adolescents?
PMID- 17026636
TI - Law as a tool to improve the health of children and adolescents in schools.
PMID- 17026637
TI - Enhancing No Child Left Behind-School mental health connections.
AB - The No Child Left Behind Act of 2001 was signed into law by President George W.
Bush in January 2002 and is regarded as the most significant federal education
policy initiative in a generation. The primary focus of the No Child Left Behind
Act is on promoting educational success for all children; however, the
legislation also contains opportunities to advance school-based mental health.
Unfortunately, the complexities of the provisions of the No Child Left Behind Act
have made it difficult for educators, stakeholders, and mental health
professionals to understand the legal and practical interface between No Child
Left Behind and the school mental health movement. Therefore, the goals of this
article are to (1) raise awareness about the challenges educators and school
mental health professionals face as a result of the implementation of No Child
Left Behind and (2) provide ideas and recommendations to advance the interface
between No Child Left Behind and school mental health, which will support key
provisions of the act and the growth of the field.
PMID- 17026638
TI - Implementation of an aggressive random drug-testing policy in a rural school
district: Student attitudes regarding program fairness and effectiveness.
AB - School districts are increasingly initiating random drug-testing (RDT) programs
in an effort to curb substance-use rates among students, yet little is known
about student attitudes toward RDT and potential obstacles to program acceptance
and effectiveness. The authors surveyed 1011 9th through 11th grade students in 2
rural high schools in North Florida regarding the pending implementation of one
of the most aggressive RDT programs in the nation. A significant majority of
students predicted that RDT would be effective, yet students were more clearly
divided in their perceptions of the fairness and the accuracy of testing. Student
perceptions of whether there is a drug problem at their school proved to be a
robust predictor of perceptions of policy fairness. Student substance-use rates
were more limited predictors of policy effectiveness and fairness. These results
may prove useful to school administrators, health professionals, and policy
makers seeking to build acceptance for RDT in their schools.
PMID- 17026639
TI - Assessing the use of school public address systems to deliver nutrition messages
to children: Shape up Somerville--audio adventures.
AB - Given the current childhood obesity epidemic, it is especially important to find
effective ways to promote healthful foods to children. School public address (PA)
systems represent an inexpensive and a replicable way of reaching children with
health messages. To test the effectiveness of this channel, messages were created
to promote 2 dried bean (legume) dishes that had been added to the school lunch
menu. Six elementary schools were pair matched, and 1 school from each pair was
randomly chosen to play the messages. The impact of the intervention on choice of
the 2 new entrees was assessed. Results indicate that for all schools combined,
choice was not significantly affected. However, compared to their matched control
schools, choice was significantly higher in the school that received the highest
dose of the intervention and was significantly lower in the school that received
the lowest dose. Choice was not changed in the school that received an
intermediate dose. These results suggest that PA systems show promise as an
effective and appropriate communications channel but only in schools that are
able to play messages frequently.
PMID- 17026640
TI - Bullying and smoking: Examining the relationships in Ontario adolescents.
AB - Using data from the 2003 Ontario Student Drug Use Survey (Centre for Addiction
and Mental Health, Toronto), the relationships between bullying and smoking in
adolescents were examined. A representative sample of 3314 grade 7-12 students
was included in the analysis. Models were adjusted for confounders identified in
the current literature. Multinomial logistic regression showed that current
smokers were more likely to be bullies than nonsmokers (relative risk ratio =
2.3, p < .001); being a current smoker was not associated with being a victim or
a bully/victim (one who is both a bully and a victim). Moreover, gender was found
to modify the effect of smoking on bullying status. Female smokers were more
likely to be bullies and bully/victims than nonsmokers while there were no
statistically significant differences for males. The associations between
bullying status and smoking are consistent with those found in a multinational
World Health Organization survey of adolescent health. Findings of the study
suggested that girls were at much higher risk for involvement in bullying if they
smoked, although girls were less frequently involved in bullying.
PMID- 17026642
TI - Assuring the safety of severely food allergic children in school.
PMID- 17026641
TI - Validating an asthma case detection instrument in a Head Start sample.
AB - Although specific tests screen children in preschool programs for vision,
hearing, and dental conditions, there are no published validated instruments to
detect preschool-age children with asthma, one of the most common pediatric
chronic conditions affecting children in economically disadvantaged communities
of color. As part of an asthma education intervention, a 15-item Brief
Respiratory Questionnaire (BRQ) was developed to detect children with probable
asthma in Head Start and subsidized preschool settings in communities with high
asthma prevalence and associated morbidity. Preschool personnel administered the
BRQ to consenting parents of 419 enrolled children. Trained interviewers
administered validation interviews (VALs) to parents of 149 case-positive
children and 51 case-negative children. Three physicians independently assessed
deidentified summaries of the VALs that captured responses about signs and
symptoms of asthma, diagnosis and treatment, and use of medical services. The
physicians' assessments of the summarized VALs were the validated standard to
which the BRQ classifications were compared. A simple algorithm of 4 items was
identified that can be administered and scored by nonmedical preschool personnel
in less than 5 minutes. The chance-corrected agreement between these 4 items of
the BRQ and the VAL was good: kappa, .73 (95% confidence interval, 0.62-0.84);
specificity, 96%; sensitivity, 73%; and positive predictive value, 97%. The BRQ
appears to be a valid instrument for detecting children with probable asthma in
Head Start and other subsidized preschool settings in communities with high
prevalence of asthma.
PMID- 17026644
TI - Contrast nephropathy following computed tomography angiography of the chest for
pulmonary embolism in the emergency department.
AB - OBJECTIVE: To estimate the frequency of contrast nephropathy after computed
tomography angiography (CTA) to rule out pulmonary embolism (PE) in the emergency
department (ED) setting. METHODS: We prospectively followed patients undergoing
CTA for PE, while in the ED, for 45 days. Patients who refused follow-up or were
receiving hemodialysis were excluded. Severe renal failure was defined as an
increase in creatinine > or = 3.0 mg dL(-1) or a need for hemodialysis within the
follow-up period. Patients were also followed for laboratory-defined contrast
nephropathy, defined as an increase in creatinine of > 0.5 mg dL(-1) or > 25%,
within seven days following CTA. RESULTS: A total of 1224 patients were followed,
and 354 [29%, 95% confidence interval (CI): 26-32%] patients had paired (preCTA
and post-CTA) creatinine measurements. None developed renal failure (0/1224; 0%,
CI: 0-0.3%). 44 patients developed laboratory-defined contrast nephropathy,
corresponding to an overall frequency of 4% (44/1224; CI: 3-5%) and 12% (44/354;
95% CI: 9-16%) among those with paired creatinine measurements. CONCLUSIONS:
Following CTA for PE, the incidence of severe renal failure was very low, but the
incidence of laboratory-defined contrast nephropathy (4% overall and 12% of those
with paired measurements) was higher than expected.
PMID- 17026645
TI - Value of D-dimer testing to decide duration of anticoagulation after deep vein
thrombosis: yes.
PMID- 17026646
TI - Performance of quantitative D-dimer methods: results of the Italian external
quality assessment scheme.
PMID- 17026647
TI - Platelet activation and cardiovascular outcomes in acute coronary syndromes.
PMID- 17026648
TI - Platelet hyperactivity and risk of recurrent thrombosis.
PMID- 17026649
TI - Attempts to make sense of the antiphospholipid syndrome.
AB - Many investigators have been intrigued by the paradoxical association of a
circulating anticoagulant, first called lupus anticoagulant by Feinstein and
Rapaport [1], with a tendency to develop thrombosis, as initially described by
Walter Bowie [2]. Work in Leuven on this topic started when Luis Carreras, an
Argentinian hematologist, joined the laboratory of blood coagulation at this
university in 1979. At that time, the head of the laboratory was Marc Verstraete.
Luis had a particular interest in antibody-mediated coagulation disorders, and
had prepared reviews on thrombosis and thrombocytopenia induced by heparin [3]
and on the lupus inhibitor [4]. In Leuven, he joined Jos Vermylen, senior member
of the laboratory, and an internist with particular interest in hemostasis,
thrombosis and vascular disease. As such, Professor Vermylen was involved in both
laboratory research and patient care.
PMID- 17026650
TI - Experimental studies on the nature of sensitive skin.
AB - BACKGROUND: In the USA, Europe and Japan 40 to 50% of women report that they have
sensitive skin, defined as abnormal sub-clinical sensory responses to drugs,
cosmetics and toiletries in the absence of visible signs of irritation. Itching,
burning, stinging and tightness are the commonest complaints, which mainly
afflict women. Manufacturers of skin care products have made available a large
variety of products which are designed for persons with sensitive skin. Such
products are not required by regulatory agencies to submit evidence of safety and
efficacy, allowing marketers to make claims that are often exaggerated,
irrational and even preposterous. The consumer with self-assessed sensitive skin
has no way of judging which products are likely to be most beneficial and least
harmful. The marketplace is awash with products for which there is no evidence
that the rosy claims have been substantiated by appropriate testing procedures.
There is no internationally accepted consensus regarding the criteria which
define sensitive skin. Many papers have been published in the last 15 years,
mainly originating from industry, which express widely differing views regarding
what constitutes sensitive skin. For some, any adverse reaction to a product
topically applied to sensitive skin, including breakouts, redness, scaling etc.,
a panoply of adverse reactions which is virtually meaningless. Others include
environmental factors as causative, including cold, dry wind, heat and high
humidity, solar radiation, etc., which add to the manifest complexities of the
subject. METHODS: This is the first paper in a series which provides a
comprehensive review of the subject, emphasizing the all too many controversies
and confusions arising from the lack of a consensus regarding the identification,
classification, epidemiology, prevalence and pathogenesis of sensitive skin.
Sensitive skin is a biologic reality and not a psychological, fashionable fantasy
on the part of impressionable women. RESULT/CONCLUSION: There is an urgent
necessity to establish rigorous methodologies for estimating the quality and
severity of sensitive skin, a heterogeneous condition involving multi-factorial
factors. Subsequent papers in this series will describe in detail the
experimental approach our group has used to bring some clarity and credibility to
this querulous, but important subject.
PMID- 17026651
TI - Assessment of anti-inflammatory activity of Poria cocos in sodium lauryl sulphate
induced irritant contact dermatitis.
AB - OBJECTIVE: In the present study, we evaluated the anti-inflammatory activity of
Poria cocos (PoCo) on experimentally induced irritant contact dermatitis (ICD) in
a repeated sodium lauryl sulphate (SLS) irritation model. METHODS: The anti
irritative effect of PoCo was evaluated with a visual score and quantified by non
invasive bioengineering methods, namely chromametry and transepidermal water
loss. Three concentrations of PoCo in base cream DAC (amphiphilic emollient;
German pharmacopoeia) were tested in a 4-day repetitive irritation test using
SLS. RESULTS: A statistically significant anti-inflammatory activity was observed
for PoCo by all three methods when applied in parallel to the induction period of
ICD. Application of PoCo after induction of ICD once a day for 5 days, starting
just at the end of 4 days, was without any effect. CONCLUSION: An anti
inflammatory efficacy of PoCo on the elicitation phase of the ICD induced by
repeated SLS test could be observed and quantified by three independent, non
invasive biophysical assessment parameters. This effect can be explained by its
influence on pro-inflammatory enzymes, namely phospholipase A2.
PMID- 17026652
TI - Acyclovir concentrations in the skin of humans after a single oral dose assessed
by in vivo cutaneous microdialysis.
AB - BACKGROUND/PURPOSE: Acyclovir is a synthetic deoxyguanosine analogue used in the
treatment of certain viral diseases. This drug is effective primarily against
Herpes simplex virus, Varicella zoster virus and to a lesser extent against
Epstein-Barr virus and cytomegalovirus. The aim of the study was to determine the
acyclovir concentrations in plasma and skin (cutaneous microdialysate) and to
compare its penetration into real (skin) and theoretical peripheral compartment
after administration of a single 0.4 g oral dose. METHODS: To evaluate the skin
concentrations of the examined agent in 10 healthy male volunteers linear
microdialysis probes with 2 kDa molecular-weight cut-off were inserted
intradermally and were perfused with Ringer solution up to 6 h after drug
ingestion. RESULTS: The mean maximum acyclovir concentrations in the plasma, skin
and theoretical peripheral compartment were 3.16+/-0.86, 0.94+/-0.34 and 1.85+/
0.69 micromol/L, respectively, and were achieved after 1.6+/-0.4, 2.4+/-0.3 and
3.7+/-0.7 h. The degree of penetration into the real (skin) and theoretical
peripheral compartment was 0.36+/-0.15 and 0.74+/-0.12, respectively, and the
differences were statistically significant. Similarly, also, the maximum
concentration, time to maximum concentration and area under the concentration
time curve differed significantly between the plasma and skin as well as between
the skin and the theoretical peripheral compartment. CONCLUSIONS: In selected
cases skin concentrations should be determined rather than those in blood plasma
when studying the distribution of orally administered drugs. Evaluation of
acyclovir concentrations in the skin cannot be replaced by the calculation of the
theoretical peripheral compartment.
PMID- 17026653
TI - Measurement of oedema in irritant-exposed skin by a dielectric technique.
AB - BACKGROUND: Easily applicable water-specific instruments measuring local oedema
in skin are not available. The aim of this study is to demonstrate quantitative
assessment of skin oedema with the dielectric technique by measuring increase of
skin water content related to sodium lauryl sulphate (SLS)-induced irritant
contact dermatitis. METHODS: Irritant skin reaction and resulting oedema were
induced by an irritant patch test on volar forearms in 12 healthy volunteers with
the application of 1% SLS for 6 h. After occlusion the volunteers were divided
into two groups: the patch test site of group I (six volunteers) received no
treatment other than a base cream for the skin reaction, while for group II (six
volunteers) a strong corticosteroid (clobetasol propionate) was applied on the
irritant skin. During a follow-up of 72 h, erythema was scored visually, and
irritant-induced oedema was measured with a novel water-specific instrument
MoistureMeter-D. RESULTS: In the untreated irritant skin, a maximum increase of
45% in skin water content was found at 10 h postocclusion and water content was
still elevated at 72 h. With these persons, the degree of oedema agreed well with
the ultrasound-measured skin thickness (P=0.053). In the corticosteroid-treated
skin, an increase of 8% in water content was measured during 72 h but there was
no correlation between oedema and skin thickness. There was no correlation
between erythema and oedema in untreated or corticosteroid-treated skin.
CONCLUSION: The new instrument can easily be applied for noninvasive quantitative
evaluation of local oedema and fluid retention in irritant-exposed skin.
PMID- 17026654
TI - Moisturizing effect of cosmetic formulations containing Aloe vera extract in
different concentrations assessed by skin bioengineering techniques.
AB - BACKGROUND/PURPOSE: The polysaccharide-rich composition of Aloe vera extracts
(Aloe barbadensis Miller), often used in cosmetic formulations, may impart
moisturizing properties to the product. The aim of this study was to evaluate the
effect of cosmetic formulations containing different concentrations of freeze
dried Aloe vera extract on skin hydration, after a single and a 1- and 2-week
period of application, by using skin bioengineering techniques. METHODS: Stable
formulations containing 5% (w/w) of a trilaureth-4 phosphate-based blend were
supplemented with 0.10%, 0.25% or 0.50% (w/w) of freeze-dried Aloe vera extract
and applied to the volar forearm of 20 female subjects. Skin conditions in terms
of the water content of the stratum corneum and of transepidermal water loss
(TEWL) (Corneometer CM 825 and Tewameter TM 210) were analysed before and after a
single and 1- and 2-week period of daily application. RESULTS: After a single
application, only formulations supplemented with 0.25% and 0.50% (w/w) of Aloe
vera extract increased the water content of the stratum corneum, while after the
2-week period application, all formulations containing the extract (0.10%, 0.25%
and 0.50%) had the same effect, in both cases as compared with the vehicle. TEWL
was not modified after a single and after 1- and 2-week period of application,
when compared with the vehicle. CONCLUSION: Our results show that freeze-dried
Aloe vera extract is a natural effective ingredient for improving skin hydration,
possibly through a humectant mechanism. Consequently, it may be used in
moisturizing cosmetic formulations and also as a complement in the treatment of
dry skin.
PMID- 17026655
TI - Kinetics of blood flow during healing of excisional full-thickness skin wounds in
pigs as monitored by laser speckle perfusion imaging.
AB - BACKGROUND/PURPOSE: The laser speckle perfusion imaging (LSPI) system is a new,
non-invasive technique for rapidly and reproducibly measuring tissue perfusion.
The high resolution and frame rate of the LSPI overcome many of the limitations
of traditional laser Doppler imaging techniques. Therefore, LSPI is a useful
means for evaluating blood flow in a variety of situations. The present study
investigates the ability of the LSPI system to detect temporal changes in blood
flow during the healing of cutaneous wounds in a well-characterized animal model.
METHODS: Full-thickness excisional skin wounds (2 x 2 cm) were created on the
backs of juvenile female red Duroc pigs. Every week post-injury, the wounds were
measured and photographed, and normalized blood flow values were determined using
the LSPI system. RESULTS: Tissue perfusion values were available after complete
re-epithelialization and removal of the eschar, at day 21. At this point, wound
blood flow was significantly elevated as compared with the surrounding,
uninvolved skin. Wound blood flow declined steadily during healing, and
approached normal values by day 35 post-injury. CONCLUSION: The kinetics of blood
flow during excisional wound healing in the red Duroc model are comparable with
that previously observed in laser Doppler imaging of healing human skin wounds
and hypertrophic scars. These results therefore confirm that the red Duroc is a
good model of human wound healing, and further indicates that the LSPI is an
excellent technique for evaluating angiogenesis and neovascularization during
healing in this and other models.
PMID- 17026656
TI - Characterization and quantification of the skin radiance through new digital
image analysis.
AB - BACKGROUND/AIMS: The individual perception of the radiance is difficult to define
and quantify because it often includes physiological and psychological
attributes. Although if they are differences in the perception of the skin
radiance, dermatologists and experts in cosmetology consider that the complexion
must reflect the general health of an individual. The aim of this work was to
determine existing conditions of skin radiance via digital image analysis,
consumer's perception and experts' evaluation, and propose a mathematical model
to quantify the global radiance phenomenon. METHODS: A round table meeting was
organized in order to have free discussions about skin radiance. The qualitative
assessment of skin radiance was carried out using a self-assessment questionnaire
constructed according to the information obtained from the round table meeting. A
simplified version of this questionnaire was proposed to experts. One hundred
female subjects belonging to three different age groups (20-30, 30-40, 40-50 and
>50 years old) participated in the study. Facial images were taken using a video
imaging with visual control system to ensure consistency of images among
volunteers. From these images, algorithms based on the principle of polynomial
approximation, segmentation by maximalization of the entropy and the Logarithmic
Image Processing model were required to extract skin radiance parameters.
Multiple regression analysis was used to establish, via consumer's perception of
the skin radiance and experts' evaluation studies, the degree to which each of
the independent parameters contributes to the skin radiance perception. RESULTS:
All the items of the self-assessment questionnaire explained 74% of the variation
of the skin radiance. Data from experts' analysis explained 87% of the variation
of skin radiance. In the two cases, skin radiance appeared to be independent of
age and the presence of wrinkles. From the image analysis, we observed that the
skin surface parameters explained 20% of the variation of the skin radiance
expressed by experts and 24% of the variation of the skin radiance expressed by
volunteers. As a result, about 80% of the variation is not explained by the
instrumental data. If we combine experts' analysis and instrumental data, we
obtain a mathematical model that explains 92% of the variation of the skin
radiance. CONCLUSION: The questionnaire constructed from this brainstorming
session allowed volunteers and experts to judge their perception of skin radiance
more precisely. Video imaging appears as an interesting method to quantify visual
properties of the skin and to visualize what the consumer perceives of skin
radiance. However, the mathematical model proposed from the skin surface
parameters analysis does not totally explain the global perception of skin
radiance. In the future, it will be necessary to develop new data-processing
programs to quantify subjective parameters in order to validate our mathematical
model.
PMID- 17026657
TI - High-resolution optical coherence tomography as a non-destructive monitoring tool
for the engineering of skin equivalents.
AB - BACKGROUND: Three dimensional skin equivalents are widely used in
dermatopharmacological and toxicological studies and as autologous transplants in
wound healing. In pharmacology, there is tremendous need for monitoring the
response of engineered skin equivalents to external treatment. Transplantation of
skin equivalents for wound healing requires careful verification of their quality
prior to transplantation. Optical coherence tomography (OCT) is a non-contact,
non-destructive imaging technique for living tissues offering the potential to
fulfill these needs. This work presents an analysis of OCT for high-resolution
monitoring of skin equivalents at different stages during the culture process.
METHODS: We developed a high-resolution OCT imaging setup based on a commercially
available OCT system. A broadband femtosecond laser light source replaces the
original superluminescence diode. Tomograms of living skin equivalents were
recorded with an axial resolution of 3 mum and correlated with histology and
immunofluorescence images. Comparison with standard low-resolution OCT is
presented to emphasize the advantages of high-resolution OCT for this
application. RESULTS: OCT is particularly able to distinguish between different
layers of skin equivalents including stratum corneum, epidermal and dermal layer
as well as the basement membrane zone. The high-resolution OCT scans correlate
closely with two key benchmarks, histology and immunofluorescence imaging.
CONCLUSIONS: This study clearly demonstrates the benefits of high-resolution OCT
for identifying living tissue structure and morphology. Compared with the current
gold standard histology, OCT offers non-destructive tissue imaging, enabling high
resolution evaluation of living tissue morphology and structure as it evolves.
PMID- 17026658
TI - Reference ranges of skin micro-relief according to age in French Caucasian and
Japanese women.
AB - BACKGROUND/PURPOSE: The variation of skin surface morphological indicators
according to age has not been frequently studied. The aim of this work was to
establish French Caucasian and Japanese reference ranges of these indicators
according to age. METHODS: Two studies were performed simultaneously in Paris and
Sendai on 356 Caucasian and 120 Japanese healthy women aged from 20 to 80 years.
Skin replicas were obtained from the volar forearm and analysed by
interferometry. This analysis yielded 16 morphological indicators. Reference
ranges according to age were established using the statistical methodology
defined by Royston. RESULTS/DISCUSSION: Reference ranges were found for 15 out of
the 16 parameters for the French women as well as for the Japanese women. The
models' truthfulness will have to be confirmed using new samples, larger if
possible. Moreover, non-parametric methods will be used in order to compare the
results provided by these approaches.
PMID- 17026659
TI - Mechanobiology and force transduction in scars developed in darker skin types.
AB - BACKGROUND: Scarring is a complex process involving many cell types, cytokines
and biological pathways including mechanobiology. Some subtle mechanical
properties of skin can be assessed by measuring the speed of ultrasound shear
wave propagation. The orientation of abnormal skin tension forces can be
visualized, particularly in darker skin types, using dermoscopy showing distinct
patterns of rete ridges' conformation. AIM: To assess some mechanobiological
features of scars in darker skin types. PATIENTS AND METHODS: Large atrophic and
hypertrophic surgical scars were examined on the trunk of 35 darker skin
subjects. The surrounding skin was used as a comparator. Dermoscopic aspects were
recorded. Resonance running time measurements (RRTM) were performed using a shear
wave propagation device (Reviscometer). They were performed in four specific
directions at given angles with regard to the long axis of the scar. The minimum,
maximum and mean RRTM values were recorded at each site. RESULTS: Dermoscopy
revealed patterns of melanin deposits in scars distinct from the normal honeycomb
network seen in the surrounding skin. Hypertrophic scars showed a patchy pattern
of large macular melanoderma dispersed in a lighter background. In these cases,
low RRTM values were obtained with little variations according to the orientation
of the measurements. By contrast, atrophic scars showed a streaky laddering
melanotic pattern under dermoscopy. Higher RRTM values were often obtained,
particularly in the transversal direction of the scars. Mechanical anisotropy was
greater in the atrophic scars compared with the normal skin. DISCUSSION: Darker
skin types represent a model for visualizing the main orientation of the
epidermal rete ridges. A correlation was found between the pattern of melanized
rete ridges of scars and the main orientation of the intrinsic forces in the
skin.
PMID- 17026660
TI - Relationships between changes in mechanical properties of the skin, wrinkling,
and destruction of dermal collagen fiber bundles caused by photoaging.
AB - BACKGROUND/PURPOSE: Long-term exposure to ultraviolet (UV) radiation induces
various cutaneous changes that differ from those because of physiological aging,
including structural destruction of dermal collagen fiber bundles (DCFBs), which
comprise the major component of the dermis. Wrinkling, a representative change in
skin surface associated with photoaging, is often seen at the corners of the eyes
and in the space between the eyebrows. These are locations where the skin
contracts repeatedly and routinely. Lowered resiliency to skin contraction
induced by marked structural changes in DCFBs may represent one cause of photo
induced wrinkles. Using animal models of photoaging, changes in mechanical
properties of the skin caused by UV irradiation were measured, and relationships
between UV-induced changes were analyzed. METHODS: Animal models of photoaging
were prepared by irradiating hairless mice with UVB light. Dorsal skin surface
replicas of animals were taken using silicon rubber, and volume of wrinkles was
calculated using an image analyzer. Stress of the skin against horizontal
contraction was measured using a new device called the Resiliometer. Three
dimensional organization of dermal collagen structures in skin samples collected
from the back of each animal was observed under scanning electron microscopy, and
compactness of DCFBs was assessed from electron micrography. RESULTS: With time
and therefore increasing UV dose, deep wrinkles formed on the backs of mice.
Volume of wrinkles peaked at 8 weeks. All parameters obtained from Resiliometer
measurements were increased by irradiation. DCFB structure was degraded in a
radiation dose-dependent manner. DCFB grading was significantly correlated with
each Resiliometer parameter. Significant correlations were also observed between
each Resiliometer parameter and volume of wrinkles. CONCLUSION: Stress of the
skin against horizontal contraction obtained using the Resiliometer changes
following UV irradiation, correlating with photo-induced wrinkling and
destruction of DCFBs. These results support the hypothesis that changed force of
restitution to skin contraction induced by marked structural changes in DCFBs
represents one cause of photo-induced wrinkles. The resiliometric parameter may
offer a good indicator for monitoring the condition of DCFB structure, as changes
in these would induce failure in restitution to skin contraction, leading to
wrinkling.
PMID- 17026661
TI - Fluorescence digital photography of acne using a light-emitting diode
illuminator.
AB - BACKGROUND/PURPOSE: The fluorescence findings of several dermatological diseases,
such as erythrasma, tinea versicolor, and acne are helpful for diagnosis and
follow-up. However, many experience difficulty taking photographic images of
fluorescence. The aim of this study was to develop a 405 nm light-emitting diode
(LED) system for fluorescence digital photography of acne and to determine
whether such a diode can be used to evaluate acne. METHODS: Eight healthy acne
patients were compared with controls by fluorescence digital photography using a
digital camera equipped with a 405 nm LED illuminator. Digital photographs were
taken by two different ways of exposure, i.e. appropriate exposure level and
longer exposure. One side of the nose, cheek, and glabella was compared. The
numbers and extents of fluorescence dots were counted and measured. As normal
controls, seven individuals with apparent oiliness and no acne were enrolled.
RESULTS: Red fluorescent facial dots were observed and photographed digitally
using the 405 nm LED illuminator. These were more numerous and extensive on the
glabella and cheeks of acne patients. CONCLUSION: Fluorescence digital
photography of acne was successfully performed using a 405 nm LED illuminator.
This illuminator could be used for acne evaluations.
PMID- 17026663
TI - Application of a pigment measuring device--Mexameter--for the differential
diagnosis of vitiligo and nevus depigmentosus.
AB - BACKGROUND/PURPOSE: Vitiligo and nevus depigmentosus (ND) present similar
hypopigmented macules with significantly different prognoses. Although the
distinction between the two diseases is important, differential diagnosis relies
on medical history and physical examination, which is far from decisive in some
cases. The Mexameter is an objective skin color-measuring device, and has been
reported to provide a reproducible and sensitive means of quantifying small skin
color differences. In this study, we investigated the usefulness of a Mexameter
for discriminating these diseases. METHODS: A selection of 202 hypopigmented skin
lesions (182 from vitiligo and 20 from ND) were the objects of this study. Using
a Mexameter, MIs were obtained from lesions and symmetrically located control
skin. RMIs, ratios of the MIs of lesional skins to control skins, were
calculated. RESULTS: The mean MIs and RMIs were significantly different for
vitiligo and ND. The mean RMI of ND lesions was 74+/-13, which was significantly
higher than that of vitiligo lesions (50+/-24). No ND lesion had an RMI of <50%.
CONCLUSION: This study shows that the Mexameter, an objective pigment-measuring
device, can be used to achieve a more accurate diagnosis of hypopigmentary
disorders, and that the relative melanin index (RMI), which represents the
relative pigment levels, might be a more effective parameter than the melanin
index (MI) itself for comparing pigmentation differences.
PMID- 17026662
TI - Hand-held pulsed photothermal radiometry system to estimate epidermal temperature
rise during laser therapy.
AB - BACKGROUND/PURPOSE: During laser therapy of port wine stain (PWS) birthmarks in
human skin, measurement of the epidermal temperature rise (DeltaT(epi)) is
important to determine the maximal permissible light dose. In order to measure
DeltaT(epi) on a specific PWS skin site, we developed an AC-coupled hand-held
pulsed photothermal radiometry (PPTR) system, which overcomes the in vivo
measurement limitations of bench-top systems. METHODS: The developed hand-held
PPTR system consists of an infrared (IR) lens, AC-coupled thermoelectrically
cooled IR detector, laser hand-piece holder, and positioning aperture. The raw AC
coupled signal was integrated to obtain a higher signal-to-noise ratio (SNR). The
experimental temperature difference (DeltaT) calibration was compared with
theoretical computations. In vitro and in vivo measurements of DeltaT were
performed with a tissue phantom as a function of radiant exposure and human
subject as a function of melanin concentration, respectively. RESULTS: The
integrated AC-coupled signal provided higher SNR as compared with the raw AC
coupled signal. The experimental DeltaT calibration resulted in good agreements
with the theoretical results. The in vitro and in vivo results also presented
good agreements with theory. CONCLUSIONS: A fiber-free, hand-held AC-coupled PPTR
system is capable of accurate epidermis temperature rise (DeltaT(epi))
measurements of human skin during pulsed laser exposure.
PMID- 17026664
TI - A non-invasive method for the in vivo determination of skin antioxidant capacity
(IAC-S).
AB - BACKGROUND/PURPOSES: Skin antioxidant network protects cells against oxidative
injury and prevents the production of oxidation products. When oxidative stress
overwhelms the skin antioxidant capacity, the subsequent modification of the
cellular redox apparatus leads to an alteration of cell homeostasis leading to
degenerative processes. In the dermocosmetic field, the topical application of
antioxidants is often suggested as a possible strategy to prevent and modulate
oxidative skin damages. Continuing our studies addressed to set-up new bio
engineering protocols for the claim substantiation of antioxidant cosmetic
products, we have developed a new non-invasive methodology for the evaluation of
antioxidants cosmetics ingredients and finished products. METHODS: The effects of
a pre-treatment on forearm skin with an antioxidant ingredient were investigated
on 15 volunteers, in a double-blind randomised fashion. A non-invasive method was
devised that comprises the collection of forehead SC layers of the pre-treated
area and control and the next evaluation of skin antioxidant capacity (IAC-S) by
a luminescence-based method. RESULTS: The results showed that the antioxidant
preparation was able to increase, to a statistically significant extent (P<0.01),
the IAC-S in comparison with the control area. The data were confirmed (P<0.05)
by comparison with a method, previously developed by us, based on DermAnalyzer.
CONCLUSIONS: In view of the simplicity and reliability of the method here
presented, this new technique is proposed as a possible tool for the routine
evaluation of in vivo efficacy of antioxidant functional ingredients and finished
products.
PMID- 17026665
TI - Phototrichogram findings in women with androgenetic alopecia.
AB - BACKGROUND/PURPOSE: Androgenetic alopecia (AGA) in women is characterized by
diffuse thinning in the frontal and parietal areas of the scalp; preservation of
the frontal hairline is norm. Hair over the occipital scalp is preserved. The
purpose of this work was to investigate the findings of phototrichogram (PTG) of
the affected and the spared areas in women with AGA and to compare them with
those of healthy subjects. METHODS: Twenty-two controls and 60 untreated women
with AGA (32 with Ludwig I, 28 with Ludwig II) were included in this study. Hair
density, percentages of thin hair, and non-growing hair were estimated both on
the midscalp and on the occiput by using PTG with digital camera attached to a
dermoscope. RESULTS: In the control group, hair density was higher on the
midscalp than the occiput. In AGA groups, hair density was lower on the midscalp
than the occiput and percentages of thin hair and non-growing hair were higher on
the midscalp than the occiput. These findings were more prominent in Ludwig II
group. In the occiput there were findings mimicking the changes seen on the
midscalp. These were less striking than those seen on the midscalp yet the
difference between the control and Ludwig II group was statistically significant.
CONCLUSION: We concluded that the hair is not equally distributed on the scalp,
the occiput may be affected in females with AGA and further studies are necessary
to support these findings.
PMID- 17026667
TI - Epitheliocystis in fish.
AB - Epitheliocystis is a condition affecting the gills and skin of fish, which has
been reported from more than 50 freshwater and marine species. It is caused by
intracellular Gram-negative bacteria. Mortalities have been associated with
epitheliocystis infections in cultured fish. This review provides an update of
our current understanding of this condition, including characterization of the
pathogen using immunohistochemical and molecular studies. In most fish species
the epitheliocystis agent was negative to an antibody specific for chlamydial
genus-specific lipopolysaccharide antigen. Recently, four epitheliocystis agents
from four different fish species have been characterized using molecular
analysis. While they all belong to the order Chlamydiales, in a lineage separate
from the Chlamydiaceae, they are distinct organisms and similarity analysis
showed that they had highest similarity values with other chlamydia-like bacteria
isolated from various sources, including humans or pig. This confirms the high
diversity and host specificity of the pathogen. Further molecular analysis should
result in an increased understanding of this condition. To date the pathogen has
not been cultured, making experimental studies difficult. High stocking
densities, presence of nutrients, season, temperature and fish age have been
identified as potential risk factors for the manifestation of this condition.
PMID- 17026666
TI - Keep the traffic moving: mechanism of the Hsp70 motor.
AB - Hsp70s are ubiquitous chaperones that use ATP hydrolysis to drive a variety of
protein processing reactions, including a number of steps in protein trafficking.
Recent studies have shed light on how ATP might generate conformational changes
in an Hsp70 molecule and how such changes might be harnessed to drive processes
as diverse as protein import into subcellular organelles and uncoating of
clathrin-coated vesicles.
PMID- 17026668
TI - Pre-exposure to infectious hypodermal and haematopoietic necrosis virus or to
inactivated white spot syndrome virus (WSSV) confers protection against WSSV in
Penaeus vannamei (Boone) post-larvae.
AB - Larvae and post-larvae of Penaeus vannamei (Boone) were submitted to primary
challenge with infectious hypodermal and haematopoietic necrosis virus (IHHNV) or
formalin-inactivated white spot syndrome virus (WSSV). Survival rate and viral
load were evaluated after secondary per os challenge with WSSV at post-larval
stage 45 (PL45). Only shrimp treated with inactivated WSSV at PL35 or with IHHNV
infection at nauplius 5, zoea 1 and PL22 were alive (4.7% and 4%, respectively)
at 10 days post-infection (p.i.). Moreover, at 9 days p.i. there was 100%
mortality in all remaining treatments, while there was 94% mortality in shrimp
treated with inactivated WSSV at PL35 and 95% mortality in shrimp previously
treated with IHHNV at N5, Z1 and PL22. Based on viral genome copy quantification
by real-time PCR, surviving shrimp previously challenged with IHHNV at PL22
contained the lowest load of WSSV (0-1x10(3) copies microg-1 of DNA). In
addition, surviving shrimp previously exposed to inactivated WSSV at PL35 also
contained few WSSV (0-2x10(3) copies microg-1 of DNA). Consequently, pre-exposure
to either IHHNV or inactivated WSSV resulted in slower WSSV replication and
delayed mortality. This evidence suggests a protective role of IHHNV as an
interfering virus, while protection obtained by inactivated WSSV might result
from non-specific antiviral immune response.
PMID- 17026669
TI - Pathogenicity of Edwardsiella tarda to olive flounder, Paralichthys olivaceus
(Temminck & Schlegel).
AB - The LD50 and cytotoxic and enzymatic activities of both cells and extracellular
products (ECPs) of eight Edwardsiella tarda strains were determined and their
bacterial superoxide dismutase gene (sodB) and catalase gene (katB) were
sequenced. Strains were also examined for their ability to resist the immune
responses of olive flounder, Paralichthys olivaceus. LD50 values of strains
(FSW910410, KE1, 2, 3, 4, 5 and 6) in olive flounder ranged between 10(2.5) and
10(5.3) cfu (colony forming units) per fish. Unlike the avirulent strain SU100
(LD50>or=10(7)), all pathogenic strains were able to survive in flounder serum
and head kidney leucocytes (except for KE2). The virulent strains possessed type
I sodB and katB, whereas SU100 had type II sodB but not katB. However, there was
no difference between avirulent and virulent strains in haemolytic and cytotoxic
activities. The results of this study demonstrated that the ability of E. tarda
to resist complement activity and phagocytosis is conferred by its superoxide
dismutase and catalase, which thus play an essential role in the pathogenicity of
this bacterium. In addition genotyping of sodB and kat B proved to be a very
useful tool to distinguish virulent from avirulent strains.
PMID- 17026670
TI - Isolation of viral haemorrhagic septicaemia virus from muskellunge, Esox
masquinongy (Mitchill), in Lake St Clair, Michigan, USA reveals a new sublineage
of the North American genotype.
AB - Viral haemorrhagic septicaemia virus (VHSV) was isolated from muskellunge, Esox
masquinongy (Mitchill), caught from the NW portion of Lake St Clair, Michigan,
USA in 2003. Affected fish exhibited congestion of internal organs; the inner
wall of the swim bladder was thickened and contained numerous budding, fluid
filled vesicles. A virus was isolated using fish cell lines inoculated with a
homogenate of kidney and spleen tissues from affected fish. Focal areas of cell
rounding and granulation appeared as early as 24 h post-inoculation and expanded
rapidly to destroy the entire cell sheet by 96 h. Electron microscopy revealed
virions that were 170-180 nm in length by 60-70 nm in width having a bullet
shaped morphology typical of rhabdoviruses. The virus was confirmed as VHSV by
reverse transcriptase-polymerase chain reaction. Sequence analysis of the entire
nucleoprotein and glycoprotein genes revealed the virus was a member of the North
American genotype of VHSV; however, the isolate was sufficiently distinct to be
considered a separate sublineage, suggesting its origin may have been from marine
species inhabiting the eastern coastal areas of the USA or Canada.
PMID- 17026671
TI - Efficacy of emamectin benzoate against sea lice infestations of Atlantic salmon,
Salmo salar L.: evaluation in the absence of an untreated contemporary control.
AB - The efficacy of emamectin benzoate (SLICE) against sea lice infestations of
Atlantic salmon, Salmo salar L., is typically assessed using untreated fish, or
fish treated with alternative therapeutants, as controls. The State of Maine,
USA, is currently under active management for the OIE-notifiable pathogen,
infectious salmon anaemia virus (ISAV); consequently, neither control group is
feasible in this region. Untreated salmon risk extensive damage from the
ectoparasites, and threaten to increase vector-borne exposure or susceptibility
of farms to ISAV; and the only treatment presently available in Maine is SLICE.
However, because sea lice infestations are unlikely to resolve spontaneously, and
response to treatment occurs within weeks, use of a pretreatment baseline is a
reasonable alternative for confirmatory studies. We evaluated SLICE efficacy on
Atlantic salmon farms in Cobscook Bay 2002-2005, in the absence of untreated
controls, using pretreatment lice loads as a reference for calculation. Maximum
efficacy ranged from 68% to 100% reduction from initial levels. Time-to-maximum
efficacy ranged from 1 to 8 weeks after treatment initiation. Efficacy duration,
measured between first reduction and first progressive rise in counts, ranged
from 4 to 16 weeks.
PMID- 17026672
TI - Isolation of Flavobacterium psychrophilum from sea lamprey, Petromyzon marinus
L., with skin lesions in Lake Ontario.
PMID- 17026673
TI - Susceptibility of the fish cell line SAF-1 to betanodavirus.
PMID- 17026690
TI - Allergic contact dermatitis to copolymers in cosmetics--case report and review of
the literature.
AB - Copolymers or heteropolymers are large molecules with high molecular weights
(>1000 D). They have been underestimated for a long time as to their sensitizing
capacities. Allergic contact dermatitis to 6 copolymers in cosmetics and 1 in a
medical dressing has been described; however, the nature of the hapten is still
unknown. We report a case of allergic contact dermatitis to polyvinylpyrrolidone
(PVP)/hexadecene copolymer in a purple-colored lipstick and review the literature
on allergic contact dermatitis to 7 copolymers: PVP/hexadecene, PVP/eicosene,
PVP/1-triacontene, methoxy polyethyleneglycol (PEG)-22/dodecyl glycols, methoxy
PEG-17/dodecyl glycols, phthalic anhydride/trimellitic anhydride/glycols, and
polyvinyl methyl/maleic acid anhydride.
PMID- 17026691
TI - Identification and classification of skin sensitizers: identifying false
positives and false negatives.
AB - The first step in regulatory evaluation of substances involves the identification
of their intrinsic hazards, including the potential for skin sensitization. This
is, quite properly, entirely different from assessment of the risks to human
health, which might arise from incorporation of substances in products. EU
guidance on regulations concerning the classification of skin sensitizers
suggests a range of sources of information be deployed in the hazard
identification process. These include chemical structure, predictive animal
tests, and various types of human data. Where the information is clear-cut, then
uncertainties rarely arise. However, for some materials, discordant information
arises, perhaps because the substance is on the borderline of test sensitivity
and classification (sensitizing materials of insufficient potency do not
classified according to the EU scheme), due to conflicting results in predictive
tests or for other reasons. In this study, we review data on a number of
substances where a classification decision is complicated by such discordances
and seek to use these examples to demonstrate how best to make a weight of
evidence decision on whether a substance should, or should not, be classified as
a skin sensitizer.
PMID- 17026692
TI - Not only oxidized R-(+)- but also S-(-)-limonene is a common cause of contact
allergy in dermatitis patients in Europe.
AB - Limonene, one of the most often used fragrance terpenes in any kind of scented
products, is prone to air-oxidation. The oxidation products formed have a
considerable sensitizing potential. In previous patch test studies on
consecutively tested dermatitis patients, oxidized R-limonene has been proven to
be a good and frequent indicator of fragrance-related contact allergy. The
current study extends these investigations to 6 European clinics of dermatology,
where the oxidation mixture of both enantiomers of limonene (R and S) have been
tested in 2411 dermatitis patients. Altogether, 63 out of 2411 patients tested
(2.6%) reacted to 1 or both the oxidized limonene preparations. Only 2.3% reacted
to the oxidized R-limonene and 2.0% to the oxidized S-limonene. In 57% of the
cases, simultaneous reactions were observed to both oxidation mixtures.
Concomitant reactions to the fragrance mix, colophonium, Myroxylon pereirae, and
fragrance-related contact allergy were common in patients reacting to 1 or both
the oxidized limonene enantiomers. Our study provides clinical evidence for the
importance of oxidation products of limonene in contact allergy. It seems
advisable to screen consecutive dermatitis patients with oxidized limonene 3%
petrolatum, although this patch test material is not yet commercially available.
PMID- 17026693
TI - The aetiology of eyelid dermatitis: a 10-year retrospective analysis.
AB - Few studies have examined the aetiology of eyelid dermatitis across broad
demographics. The objectives of this study were (i) to compare the diagnoses of
patients with isolated eyelid dermatitis to the diagnoses of patients with
additional sites of involvement and (ii) to determine the relevant allergens
among patients with allergic eyelid dermatitis. A retrospective analysis of 1215
patients patch tested over 10 years was conducted in this study. Compared to
patients without eyelid dermatitis, patients with this entity were more often
female. Of the 105 patients with eyelid dermatitis, 43.8% had allergic contact
dermatitis (ACD), 36.2% seborrhoeic dermatitis, 11.4% other
dermatitis/dermatoses, 7.6% irritant contact dermatitis, 3.8% psoriasis, and 2.9%
atopic eczema. With isolated eyelid dermatitis, seborrhoeic dermatitis was the
most frequent diagnosis (46.3%) followed by ACD (35.2%). Allergens commonly
causing allergic eyelid dermatitis consisted of fragrances, metals, neomycin,
oleamidopropyl dimethylamine, tosylamide formaldehyde resin, benzalkonium
chloride, and other preservatives. When evaluated according to sites of
involvement, seborrhoeic dermatitis was diagnosed most often in patients with
isolated eyelid dermatitis, but when dermatitis was distributed to facial or
other sites, ACD was the most frequent diagnosis. A majority of the causative
allergens for eyelid dermatitis are not present on the Food and Drug
Administration-approved panels available in the USA.
PMID- 17026694
TI - Nickel allergy and hand eczema--a 20-year follow up.
AB - The aim of this study was to investigate the occurrence of hand eczema after 20
years in women patch tested to nickel during childhood. In 1982-1983, 960
schoolgirls were patch tested for nickel allergy; its prevalence was found to be
9%. 20 years later, the same individuals received a questionnaire regarding hand
eczema and factors of importance for the development of hand eczema. 735 of 908
women (80.9%) answered the questionnaire. In total, 17.6% of respondents reported
hand eczema after the age of 15 years, and the 1-year prevalence was 12.8%. There
was no statistically significant difference in the occurrence of hand eczema
between the groups who had previously tested positive and negative for nickel
allergy. 38.3% of the respondents considered themselves to be nickel sensitive at
the time they answered the questionnaire; in this group, the reported prevalence
of hand eczema after age 15 was 22.5%. 31.4% of those with a history of atopic
dermatitis reported hand eczema after age 15, compared with 10.6% of those
without (P < 0.001). In conclusion, contact allergy to nickel in childhood did
not seem to increase the prevalence of hand eczema later in life.
PMID- 17026695
TI - Adverse skin reactions to personal protective equipment against severe acute
respiratory syndrome--a descriptive study in Singapore.
AB - Severe acute respiratory syndrome (SARS) was first recognized in February 2003.
It is the first severe and readily transmissible new disease to emerge in the
21st century. Healthcare workers in affected countries were exposed to the
regular use of personal protective equipment (PPE) such as the N95 mask, gloves,
and gowns. Our aim was to study the prevalence of adverse skin reactions to PPE
among healthcare workers in Singapore during the SARS outbreak. Healthcare staff
in the National Skin Centre and Tan Tock Seng Hospital were surveyed using
questionnaires. Of those asked to participate, 322 (94.7%) agreed. 14.3% of the
respondents were doctors, 73.0% nurses, and 12.7% other ancillary staff. Mean age
of respondents was 32.4 years, with the majority being women (85.7%) and Chinese
(53.7%). 109 (35.5%) of the 307 staff who used masks regularly reported acne
(59.6%), facial itch (51.4%), and rash (35.8%) from N95 mask use. 64 (21.4%) of
the 299 who used gloves regularly reported dry skin (73.4%), itch (56.3%), and
rash (37.5%). The use of PPE is associated with high rates of adverse skin
reactions. There is a need to find suitable alternatives for affected staff and
to encourage awareness among staff of the role of dermatologists in their care.
PMID- 17026696
TI - The validity of a questionnaire-based epidemiological study of occupational
dermatosis.
AB - The aim of this study was to evaluate the validity of a questionnaire and medical
anamnesis to identify persons with dermatitis in an occupational setting. The
design was a clinical epidemiological cross-sectional study. The study was
performed between the second and fourth week of January 2001. A questionnaire was
followed a week later by a medical occupational interview and a clinical
dermatological examination, including a comprehensive patch test with potential
workplace chemicals. The anamnesis and the clinical examination were made
independently by occupational and dermatological physicians, and the skin
examination was performed blinded to anamnestic data. The setting was the mother
plants of a Danish-based international company producing wind turbine systems.
The study population was a workplace cohort, highly exposed to epoxy resin
systems and other chemicals, and totalled 724 production workers at 4 facilities.
The rate of participation was 84.7%. Using enquete questions of current skin rash
against the clinical presence of dermatitis, we found a sensitivity of 22% and a
specificity of 89%, compared to 45% and 87%, respectively, when the anamnestic
work history, taken by an occupational physician, was the screening parameter.
Using 'workplace periodic prevalence' of dermatitis, we found sensitivities in
the range of 63-76% by a questionnaire and 70-83% by medical anamnesis.
Questionnaire screening by skin symptoms gave the highest values for redness, a
sensitivity of 33% and a specificity of 76%, and decreasing validity parameters
as more symptoms were added to the list of screening questions. We found that the
use of a questionnaire and medical anamnesis were problematic, when the purpose
was screening for contact dermatitis and allergy, in this industrial cohort
manufacturing reinforced plastic products. But these instruments might be useful
for epidemiological surveillance, when the questionnaire has been validated in
the given occupational setting.
PMID- 17026697
TI - IgE-mediated anaphylaxis from chlorhexidine: diagnostic possibilities.
PMID- 17026698
TI - Occupational airborne dermatitis from gordolobo (Verbascum densiflorum).
PMID- 17026699
TI - Contact allergy to sodium cocoamphoacetate present in an eye make-up remover.
AB - This is a case report of a contact allergic reaction on the face due to a skin
cleansing product containing the amphoteric surfactant sodium cocoamphoacetate,
occurring in an atopic woman with multiple contact sensitivities. Because of its
weak irritant properties, this surfactant is widely used in cosmetic products
intended to be used for sensitive skin, including products for intimate, and baby
hygiene.
PMID- 17026700
TI - Irritant contact dermatitis with a vasculitic-like pattern from PVP-I.
PMID- 17026701
TI - Photopatch tests: any news under the sun?
PMID- 17026702
TI - Contact allergy to propylene glycol and dodecyl gallate mimicking seborrheic
dermatitis.
PMID- 17026703
TI - Occupational contact urticaria-dermatitis by Tyrophagus putrescentiae.
PMID- 17026704
TI - Contact erythema annulare centrifugum.
PMID- 17026705
TI - PPD: is this a connubial dermatitis?
PMID- 17026706
TI - Airborne contact dermatitis to methylchloroisothiazolinone/methylisothiazolinone
in a boy.
PMID- 17026707
TI - Airborne contact dermatitis from n-alkyl dimethylbenzylammonium chloride and n
alkyl dimethylethyl-benzylammonium chloride in a detergent.
AB - Occupational airborne contact dermatitis from disinfectants are not frequent.
They are usually seen in hospitals, were the exposure is more common. We report a
case of a young woman, with an intense eczematous eruption that developed hours
after an accidental contact with a cleaning solution.
PMID- 17026708
TI - Allergic contact dermatitis from cera alba (purified propolis) in a lip balm and
candy.
PMID- 17026709
TI - Both mercaptobenzothiazole and mercapto mix should be part of the standard
series.
PMID- 17026711
TI - Somatic H1 histone accumulation and germ layer determination in amphibian
embryos.
AB - The induction of mesoderm and/or endoderm from prospective ectoderm and
dorsalization of the marginal zone mesoderm may be linked to inhibition of cell
cycling and DNA synthesis in early amphibian embryos. In turn, this may lead to
reduction of somatic H1 histone accumulation. A greater number of cell cycles and
rounds of DNA synthesis characterizes the induction of neural tissue. This is
correlated with an increase of somatic H1 histone accumulation. The number of
rounds of DNA replication may regulate the level of H1 histone accumulation and
this may have a role in germ layer determination.
PMID- 17026712
TI - Sox genes regulate type 2 collagen expression in avian neural crest cells.
AB - Neural crest cells give rise to a wide variety of cell types, including cartilage
cells in the cranium and neurons and glial cells in the peripheral nervous
system. To examine the relationship of cartilage differentiation and neural crest
differentiation, we examined the expression of Col2a1, which encodes type 2
collagen often used as a cartilage marker, and compared it with the expression of
Sox transcription factor genes, which are involved in neural crest development
and chondrogenesis. We found that Col2a1 is expressed in many neural crest
derived cell types along with combinations of Sox9, Sox10 and LSox5.
Overexpression studies reveal the activation of Col2a1 expression by Sox9 and
Sox10, and cross-regulation of these Sox genes. Luciferase assay indicates a
direct activation of the Col2a1 enhancer/promoter both by Sox9 and Sox10, and
this activation is further enhanced by cAMP-dependent kinase (PKA) signaling. Our
study suggests that the regulatory mechanisms are similar in cartilage and neural
crest differentiation.
PMID- 17026713
TI - Endo16 is required for gastrulation in the sea urchin Lytechinus variegatus.
AB - The Endo16 gene encodes a large extracellular protein with several functional
domains that provide some insight into the role of this protein during embryonic
development. We isolated the full-length cDNA sequence from Lytechinus variegatus
and utilized morpholinos to further investigate the role of Endo16 during
embryonic development in this species. Endo16-deficient embryos failed to undergo
gastrulation and the blastocoele became filled with dissociated cells after 24 h
of incubation. Moreover, there was a delay in endoderm differentiation as assayed
by staining with an antibody that recognizes Endo1. The differentiation of other
cell types including oral ectoderm, primary mesenchymal cells (PMC) and secondary
mesenchymal cells (SMC) appeared to be normal, although the patterns of protein
expression did not resemble control embryos due to the gross morphological
abnormalities elicited by the LvEndo16 morpholino. Microinjection of full-length
EGFP mRNA with the LvEndo16 morpholino-targeted sequence confirmed that this
phenotype can be attributed specifically to the loss of Endo16 protein. Taken
together, our data suggest that Endo16 may be required for the cell-extracellular
matrix (ECM) interactions that are required for endoderm differentiation in the
sea urchin embryo.
PMID- 17026714
TI - Characterization of myeloid cells derived from the anterior ventral mesoderm in
the Xenopus laevis embryo.
AB - A recent study revealed the presence of a unique population of myeloid cells in
the anterior ventral (AV) mesoderm of Xenopus laevis embryo, as characterized by
the expression of peroxidase 2 (POX2), which encodes for a leukocyte-specific
enzyme. The current report further characterized the POX2-positive cells in terms
of their contribution to hematopoiesis in tadpole and regulatory mechanism in
differentiation. Grafting experiments with cytogenetically labeled tissues
revealed that AV-derived mesoderm supplies a transient population of migrating
leukocytes in the mesenchyme of early tadpole. These cells were rarely found in
blood vessels at any stages. Using a ventral marginal zone explant system, we
demonstrated that dkk1, shown as a heart inducer in this system, has a strong
ability to induce the expression of POX2. Injection of a high dose dkk1 RNA
induced a heart marker while a low dose of dkk1 preferentially induced the
expression of POX2, suggesting that dkk1 works as a morphogen to determine the
different lineages. Overall results indicate that wnt signal inhibitors induce
leukocytes at the early neurula stage and that these cells spread to the entire
body and exist until the ventral blood island-derived leukocytes appear in the
body.
PMID- 17026715
TI - Role of ERK 1/2 signaling in neuronal differentiation of cultured embryonic stem
cells.
AB - Embryonic stem (ES) cells represent an ideal source for cell engraftment in the
damaged central nervous system (CNS). Understanding key signals that control ES
cell differentiation may improve cell type-specific differentiation that is
suitable for transplantation therapy. We tested the hypothesis that extracellular
signal-regulated kinase (ERK) 1/2 phosphorylation is an early signaling event
required for the neuronal differentiation of ES cells. Cultured mouse ES cells
were treated with an all-trans-retinoic-acid (RA) protocol to generate neurally
induced progenitor cells. Western blot analysis showed a dramatic increase in ERK
1/2 phosphorylation (p-ERK 1/2) 1-5 days after RA induction, which was attenuated
in the presence of the p-ERK 1/2-specific inhibitor UO126. Phospho-ERK 1/2
inhibition significantly reduced the number of NeuN-positive cells and the
expression of associated cytoskeletal proteins. In differentiating ES cells,
there was increased nuclear translocation of STAT3 and decreased protein
expression levels of GDNF, BDNF and NGF. STAT3 translocation was attenuated by
UO126. Finally, caspase-3 activation was observed in the presence of UO126,
suggesting that the ERK pathway also contributes to the survival of
differentiating ES cells. These data indicate that ERK 1/2 phosphorylation is a
key event required for early neuronal differentiation and survival of ES cells.
PMID- 17026716
TI - Functional demonstration of the ability of a primary spermatogonium as a stem
cell by tracing a single cell destiny in Xenopus laevis.
AB - In Xenopus, although primary spermatogonium (PG), the largest cell in the testis,
is believed to be spermatogonial stem cell by histological observations,
functional evidence has never been obtained. In the present study, we first
indicated that culture of juvenile testis in a medium supplemented with follicle
stimulating hormone resulted in no proliferation of PG. In this culture system,
early secondary spermatogonia could undergo mitotic divisions with a concomitant
decrease in their size, so that they became distinguishable in size from PG.
Because the subcutaneous environment of juveniles permitted aggregates of the
dissociated testicular cells to reconstruct the normal testis structure, we next
inserted a genetically marked PG isolated from cultured testes into the aggregate
and transplanted it subcutaneously. In this system, 73.9% of the aggregates
contained a marked PG. When we observed the aggregates 12 weeks after
transplantation, most aggregates (70.0%) contained marked PG that had self
renewed. Among these, fully growing aggregates contained many spermatogenic cells
at the later developmental stage. These results suggested that isolated PG from
the cultured testes had the ability as stem cells, and that purification of the
spermatogenic stem cells became reliable in Xenopus.
PMID- 17026717
TI - Differential growth identified in salamander larvae half-sib cohorts: survival
strategy?
AB - In this study we describe the growth of several different larval cohorts (i.e.
half-siblings of the same mother born on the same day) of a rare, xeric-adapted
salamander Salamandra s. infraimmaculata Martens, 1885, under constant density
and food conditions from birth to metamorphosis. The larvae spend the critical
first phase of their lives in water, mostly in temporary ponds. Age and weight at
metamorphosis were highly affected by varying food conditions. We have identified
six different growth modes that these larvae use, both fast growing and slow
growing. Each larval cohort was found to use 2-4 different such growth modes
regardless of their initial weight. Fast growing modes (I-III) will enable larvae
to survive dry years, and metamorphose bigger. Slow growing modes (IV-VI), used
by 8% of the larval population, will enable survival only in rainy years. These
last growth modes effect differential temporal dispersal in wet years by delaying
the emergence of postmetamorphs onto land. Distribution of growth modes in the
larval population is affected by food but not by density conditions. Late-born,
fast-growing larvae will have an advantage in dry years being able to
metamorphose and disperse, whereas the slow-growing larvae will survive only in
wet years.
PMID- 17026718
TI - Dynamics of the IncW genetic backbone imply general trends in conjugative plasmid
evolution.
AB - Plasmids cannot be understood as mere tools for genetic exchange: they are
themselves subject to the forces of evolution. Their genomic and phylogenetic
features have been less studied in this respect. Focusing on the IncW
incompatibility group, which includes the smallest known conjugative plasmids, we
attempt to unveil some common trends in plasmid evolution. The functional modules
of IncW genetic backbone are described, with emphasis on their architecture and
relationships to other plasmid groups. Some plasmid regions exhibit strong
phylogenetic mosaicism, in striking contrast to others of unusual synteny
conservation. The presence of genes of unknown function that are widely
distributed in plasmid genomes is also emphasized, exposing the existence of ill
defined yet conserved plasmid functions. Conjugation is an essential hallmark of
IncW plasmid biology and special attention is given to the organization and
evolution of its transfer modules. Genetic exchange between plasmids and their
hosts is analysed by following the evolution of the type IV secretion system.
Adaptation of the trw conjugative machinery to pathogenicity functions in
Bartonella is discussed as an example of how plasmids can change their host modus
vivendi. Starting from the phage paradigm, our analysis articulates novel
concepts that apply to plasmid evolution.
PMID- 17026719
TI - Leishmania cytosolic silent information regulatory protein 2 deacetylase induces
murine B-cell differentiation and in vivo production of specific antibodies.
AB - In previous studies, we identified a gene product belonging to the silent
information regulatory 2 protein (SIR2) family. This protein is expressed by all
Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L.
mexicana) and found to be crucial for parasite survival and virulence. In the
present study, we investigated whether a Leishmania SIR2 recombinant protein
(LmSIR2) would affect T- and B-cell functions in a murine model. In vitro
treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased
expression of CD69 on B cells. This effect was not abolished by the addition of
polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased
spleen B cell number by a factor of about approximately 1.6, whereas no
modification occurred at the level of CD4(+) and CD8(+) cells. Furthermore,
intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or
nude mice triggered the production of elevated levels of LmSIR2-specific
antibodies. The analysis of specific isotype profiles showed a predominance of
immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in
nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of
complement induced the in vitro lysis of L. infantum amastigotes. In the absence
of complement, the antibodies induced significant inhibition of amastigotes
developpement inside macrophages. Together, the current study provides the first
evidence that a Leishmania protein belonging to the SIR2 family may play a role
in the regulation of immune response through its capacity to trigger B-cell
effector function.
PMID- 17026720
TI - Comparison of cervical and blood T-cell responses to human papillomavirus-16 in
women with human papillomavirus-associated cervical intraepithelial neoplasia.
AB - Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically
cause localized mucosal infections. We therefore hypothesized that T-cell
responses to HPV antigens would be greater at sites of pathology than in the
blood. Focusing on HPV-16 because of its association with cervical cancer, the
magnitude of HPV-specific T-cell responses at the cervix was compared with those
in the peripheral blood by intracellular cytokine staining following direct ex
vivo stimulation with both virus-like particles assembled from the major capsid
protein L1, and the major HPV oncoprotein, E7. We show that both CD4(+) and
CD8(+) T cells from the cervix responded to the HPV-16 antigens and that
interferon-gamma (IFN-gamma) production was HPV type-specific. Comparing HPV
specific T-cell IFN-gamma responses at the cervix with those in the blood, we
found that while CD4(+) and CD8(+) T-cell responses to L1 were significantly
correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-gamma
responses in both T-cell subsets were significantly greater in magnitude at the
cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In
contrast, both CD4(+) and CD8(+) T-cell IFN-gamma responses to E7 were of similar
magnitude in both compartments and CD8(+) responses were significantly correlated
between these distinct immunological compartments (P = 0.04). We therefore show
that inflammatory T-cell responses against L1 (but not E7) demonstrate clear
compartmental bias and the magnitude of these responses do reflect local viral
replication but that correlation of HPV-specific responses between compartments
indicates their linkage.
PMID- 17026721
TI - Recombinant integrin CD11b A-domain blocks polymorphonuclear cells recruitment
and protects against skeletal muscle inflammatory injury in the rat.
AB - The beta2 integrin CD11b/CD18 (CR3) is a major adhesion receptor of neutrophils,
normally utilized to fend off infections. This receptor contributes, however, to
multiple forms of non-infectious inflammatory injury when dysregulated as shown
in gene knock-outs and through the use of blocking monoclonal antibodies. The
major ligand recognition site of CR3 has been mapped to the A-domain in the CD11b
subunit (CD11bA). The recombinant form of this domain exhibits a ligand binding
profile similar to that of the holoreceptor. To assess the potential anti
inflammatory activity of CD11bA as a competitive antagonist of CR3 in vivo, we
assessed its effects on a developed animal model of traumatic skeletal muscle
injury in the rat. Recombinant soluble rat CD11bA-domain fused to glutathione-S
transferase (GST) was administered intravenously in a single dose at 1 mg/kg to
nine groups of Wistar rats, five in each group, 30 min before inducing traumatic
skeletal muscle injury. Control animals received either a function-blocking anti
CD11b/CD18 monoclonal antibody (1 mg/kg), non-functional mutant forms of the
CD11bA (D140GS/AGA, T209/A, D242/A), recombinant GST or buffer alone. In control
animals, the wounded muscle showed oedema, erythrocyte extravasation and
myonecrosis both within and outside the immediate wounded area (5-10 mm zone) and
influx of neutrophils was detected 30 min post-wound, followed by a second wave 3
hr later. Wild-type CD11bA- or anti-CD11b monoclonal antibody (mAb)-treated rats
showed a comparable and significant decrease in the number of infiltrating PMN
(78 + 4%, n = 70 and 86 +/- 2%, n = 50, respectively) and preservation of the
muscular fibres outside the immediate zone of necrosis (75 + 4%, n = 70, 84 +/-
1%, n = 50, respectively), compared to controls. These data demonstrate that
CD11bA can be an effective tissue-preserving agent in acute inflammatory muscular
injury.
PMID- 17026722
TI - The value of urine specific gravity in detecting diabetes insipidus in a patient
with uncontrolled diabetes mellitus: urine specific gravity in differential
diagnosis.
AB - When a patient with diabetes mellitus presents with worsening polyuria and
polydipsia, what is a sensible, cost-effective approach? We report the unique
coincidence of type 2 diabetes mellitus and diabetes insipidus. A 46-year-old
woman with poorly controlled type 2 diabetes complained of polyuria with a daily
output of 5 L. Although urinalysis demonstrated significant glucosuria, diabetes
insipidus was suspected owing to a low urine specific gravity (1.008). The low
specific gravity persisted during a water deprivation test. Ultimately, diabetes
insipidus was confirmed when urine specific gravity and urine osmolality
normalized following desmopressin administration. This case emphasizes the
importance of accurately interpreting the urine specific gravity in patients with
polyuria and diabetes mellitus to detect diabetes insipidus.
PMID- 17026723
TI - Acquired Fanconi's syndrome associated with tenofovir therapy.
AB - Tenofovir (Viread) is a nucleotide reverse transcriptase inhibitor introduced
into the United States in 2001. It is frequently prescribed not only for its
efficacy but also for its decreased side effect profile compared with other
nucleoside analogs. It is now increasingly recognized as a cause of acquired
Fanconi's syndrome (FS) in human immunodeficient individuals. We describe a case
of a patient with AIDS, who, after starting tenofovir therapy, developed
myalgias, renal failure, and profound electrolyte abnormalities compatible with
the classic features of FS. On discontinuation of tenofovir and replacement of
electrolytes, the individual improved clinically with normalization of his renal
failure and electrolyte abnormalities. With the success of tenofovir in the anti
HIV drug market, practitioners should remain alert to the possibility of the
development of FS. Frequent urine, renal, and electrolyte parameters should be
measured at regular intervals following initiation of tenofovir therapy.
PMID- 17026724
TI - Disseminated intravascular coagulation as the presenting sign of metastatic
prostate cancer.
AB - Disseminated intravascular coagulation (DIC) is an acquired coagulation disorder
that may occur in a wide variety of clinical conditions. Suspicion of DIC should
lead to a differential diagnosis that includes primary fibrinolysis and other
bleeding diatheses such as thrombocytopenias of diverse etiology. Confirmation of
the diagnosis of DIC should always prompt a search for an underlying medical
disorder, including sepsis, severe trauma, solid and hematological malignancies,
obstetrical complications, and vascular disorders. Here, we describe an unusual
case of acute bleeding and DIC as the presenting manifestation of metastatic
prostate cancer in a 60-year-old man. Treatment with a luteinizing hormone
releasing hormone (LHRH) agonist and a short course of an antiandrogen, together
with supportive measures (i.e., clotting factors, heparin, and platelets), led to
normalization of all coagulation parameters within 1 week, and to clinical
improvement and decline in the serum level of prostate-specific antigen (PSA). We
discuss the pathogenesis, differential diagnosis, and association of DIC with
prostate cancer along with the management of this condition.
PMID- 17026725
TI - A twist on torsade: a prolonged QT interval on methadone.
AB - A woman developed a prolonged QT interval and torsade de pointes while on
methadone treatment for heroin addiction. We think methadone, or its impaired
metabolism, was the major cause for her prolonged QT interval and progression to
torsade. However, torsade is often multifactorial, as was likely so in this case.
We advise physicians treating patients taking methadone to obtain careful
medication and drug-use histories, screen for risk factors associated with long
QT syndrome, counsel patients about potential drug interactions, and measure the
QT interval before and during methadone treatment in high-risk patients.
PMID- 17026726
TI - Medical comorbidity in women and men with schizophrenia: a population-based
controlled study.
AB - BACKGROUND: Persons with persistent mental illness are at risk for failure to
receive medical services. In order to deliver appropriate preventive and primary
care for this population, it is important to determine which chronic medical
conditions are most common. OBJECTIVE: We examined chronic medical comorbidity in
persons with schizophrenia using validated methodologies. DESIGN: Retrospective
analysis of longitudinal administrative claims data from Wellmark Blue Cross/Blue
Shield of Iowa. PARTICIPANTS: Subjects with schizophrenia or schizoaffective
disorder (N=1,074), and controls (N=726,262) who filed at least 1 claim for
medical services, 1996 to 2001. MEASUREMENTS: Case subjects had schizophrenia as
the most clinically predominant psychotic disorder, based on psychiatric
hospitalization, psychiatrist diagnoses, and outpatient care. Controls had no
claims for any psychiatric comorbidity. Using a modified version of the
Elixhauser Comorbidity Index, inpatient and outpatient claims were used to
determine the prevalence of 46 common medical conditions. Odds ratios (ORs) were
adjusted for age, gender, residence, and nonmental health care utilization using
logistic regression. RESULTS: Subjects with schizophrenia were significantly more
likely to have 1 or more chronic conditions compared with controls. Adjusted OR
(95% confidence interval [CI]) were 2.62 (2.09 to 3.28) for hypothyroidism, 1.88
(1.51 to 2.32) for chronic obstructive pulmonary disease, 2.11 (1.36 to 3.28) for
diabetes with complications, 7.54 (3.55 to 15.99) for hepatitis C, 4.21 (3.25 to
5.44) for fluid/electrolyte disorders, and 2.77 (2.23 to 3.44) for nicotine
abuse/dependence. CONCLUSIONS: Schizophrenia is associated with substantial
chronic medical burden. Familiarity with conditions affecting persons with
schizophrenia may assist programs aimed at providing medical care for the
mentally ill.
PMID- 17026727
TI - Types of information physicians provide when prescribing antidepressants.
AB - BACKGROUND: Providing antidepressant information to patients may foster greater
adherence to therapy. OBJECTIVE: To assess physician information-giving while
prescribing antidepressants, and to identify factors that influence the provision
of information. DESIGN: Randomized experiment using standardized patients (SPs).
Standardized patients roles were generated by crossing 2 clinical conditions
(major depression or adjustment disorder) with 3 medication request types (brand
specific, general, or none). PARTICIPANTS: One hundred and fifty-two general
internists and family physicians recruited from solo and group practices and
health maintenance organizations; cooperation rates ranged from 53% to 61%.
MEASUREMENTS: We assessed physician information-giving by analyzing audio
recordings of interactions between physicians and SPs, and collected physician
background information by survey. Generalized estimating equations were used to
examine the influence of patient and physician factors on physicians' provision
of information. RESULTS: One hundred and one physicians prescribed
antidepressants, accounting for 131 interactions. The mean age of physicians was
46.3 years; 69% were males. Physicians mentioned an average of 5.7 specific
topics of antidepressant-related information (of a possible maximum of 11). The
most frequently mentioned topic was purpose (96.1%). Physicians infrequently
provided information about the duration of therapy (34.9%) and costs (21.4%).
Standardized patients who presented with major depression received less
information than those with adjustment disorder, and older and solo/private
practice physicians provided significantly less information to SPs. CONCLUSIONS:
Physicians provide limited information to patients while prescribing
antidepressants, often omitting critical information that may promote adherence.
Mechanisms are needed to ensure that patients receive pertinent antidepressant
information.
PMID- 17026728
TI - Brief report: incidence, etiology, risk factors, and outcome of hospital-acquired
fever: a systematic, evidence-based review.
AB - OBJECTIVES: Temperature is universally measured in the hospitalized patient, but
the literature on hospital-acquired fever has not been systematically reviewed.
This systematic review is intended to provide clinicians with an overview of the
incidence, etiology, and outcome of hospital-acquired fever. DATA SOURCES: We
searched MEDLINE (1970 to 2005), EMBASE (1988 to 2004), and Web of Knowledge.
References of all included articles were reviewed. Articles that focused on
children, fever in the developing world, classic fever of unknown origin, or
specialized patient populations were excluded. REVIEW METHODS: Articles were
reviewed independently by 2 authors before inclusion; a third author acted as
arbiter. RESULTS: Of over 1,000 studies reviewed, 7 met the criteria for
inclusion. The incidence of hospital-acquired fever ranged from 2% to 17%. The
etiology of fever was infection in 37% to 74%. Rates of antibiotic use for
patients with a noninfectious cause of fever ranged from 29% to 55% for a mean
duration of 6.6 to 9.6 days. Studies varied widely in their methodology and the
patient population studied. CONCLUSIONS: Limited information is available to
guide an evidence-based approach to hospital-acquired fever. We propose criteria
to help standardize future studies of this important clinical situation.
PMID- 17026729
TI - Morbidity and mortality conference, grand rounds, and the ACGME's core
competencies.
AB - Morbidity and Mortality (M&M) Conferences are an Accreditation Council for
Graduate Medical Education (ACGME) mandated educational series that occur
regularly at all institutions that have residency training programs. The
potential for learning from medical errors, complications, and unanticipated
outcomes is immense--provided that the focus is on education, as opposed to
culpability. The education innovation described in this manuscript is the manner
in which we have used the ACGME Outcome Project's 6 core competencies as the
structure upon which the cases discussed at our M&M conference are framed. When
presented at grand rounds in a novel format, M&M conference has not only
maintained support for the quality improvement efforts in the Department, but has
served to improve the educational impact of the conference.
PMID- 17026730
TI - Exploring the educational value of clinical vignettes from the Society of General
Internal Medicine national meeting in the internal medicine clerkship: a pilot
study.
AB - INTRODUCTION: Whether the clinical vignettes presented at the Society of General
Internal Medicine (SGIM) annual meeting could be of educational value to third
year students in the Internal Medicine clerkship has not been studied. OBJECTIVE:
To explore the relevance and learning value of clinical vignettes from the SGIM
national meeting in the Internal Medicine clerkship. SETTING: Third year
Ambulatory Internal Medicine clerkship at one academic medical center (academic
year 2005 to 2006). METHODS: Students were introduced to the clinical vignette
and oriented to the database of clinical vignettes available through the SGIM
annual meeting website. Students then reviewed 5 to 10 clinical vignettes using a
worksheet, and rated the learning value of each vignette using a 5-point Likert
scale (1=least, 5=greatest). A single investigator evaluated congruence of the
vignette with the Clerkship Directors of Internal Medicine (CDIM)-SGIM curriculum
to assess relevance. MAIN RESULTS: A total of 42 students evaluated 371 clinical
vignettes from the 2004 and 2005 meetings. The clinical vignettes were curriculum
congruent in 42.6% (n=175), and clearly incongruent in 40.4% (n=164). The mean
rating for learning value was 3.8 (+/-1.0) (5 signifying greatest learning
value). Curriculum-congruent vignettes had a higher mean learning value compared
with curriculum-incongruent vignettes (4.0 vs 3.6, Student's t-test, P=.017).
CONCLUSION: The clinical vignettes presented at the national SGIM meeting offer
clinical content that is relevant and of some educational value for third year
clerkship students. Based on this pilot study, the educational value and
strategies for their use in the clinical clerkships deserve further study.
PMID- 17026731
TI - The effect of market reform on racial differences in hospital mortality.
AB - OBJECTIVE: To determine whether racial differences in hospital mortality worsened
after implementation of a New Jersey law in 1993 that reduced subsidies for
uninsured hospital care and changed hospital payment from rate regulation to
price competition. DATA SOURCES/STUDY SETTING: State discharge data for New
Jersey and New York from 1990 to 1996. STUDY DESIGN: We used an interrupted time
series design to compare risk-adjusted in-hospital mortality rates between states
over time. Adjusting for patient characteristics, baseline interstate
differences, and common intertemporal trends, we compared the effect sizes for
whites and blacks in the following 4 groups: overall, uninsured, insured under
age 65, and Medicare patients. DATA COLLECTION/EXTRACTION METHODS: The study
sample included 1,357,394 patients admitted to New Jersey or New York hospitals
between 1990 to 1996 with stroke, hip fracture, pneumonia, pulmonary embolism,
congestive heart failure, or acute myocardial infarction (AMI). PRINCIPAL
FINDINGS: The increase in mortality in New Jersey versus New York was
significantly larger among blacks than among whites for AMI (2.4% points vs 0.1%
points, P-value for difference .026) but not for the other 6 conditions. In
groupings of conditions for which hospital admission is non-discretionary and
conditions in which admission is discretionary, we found qualitatively larger
increases in mortality for blacks but no statistically significant racial
differences among patients overall, uninsured patients, insured patients under
age 65, or Medicare patients. CONCLUSIONS: Market-based reform and reductions in
subsidies for hospital care for the uninsured in New Jersey were associated with
worsening racial disparities in in-hospital mortality for AMI but not for 6 other
common conditions.
PMID- 17026735
TI - Medical care for patients with severe and persistent mental illness.
PMID- 17026736
TI - Tough questions, even harder answers.
PMID- 17026737
TI - The inherent inequities of market-based health care reform.
PMID- 17026739
TI - Letter to the editor regarding Kho, et al.
PMID- 17026741
TI - Internal medicine specialists' attitudes towards working part-time: a comparison
between 1996 and 2004.
AB - BACKGROUND: Although medical specialists traditionally hold negative views
towards working part-time, the practice of medicine has evolved. Given the trend
towards more part-time work and that there is no evidence that it compromises the
quality of care, attitudes towards part-time work may have changed as well in
recent years. The aim of this paper was to examine the possible changes in
attitudes towards part-time work among specialists in internal medicine between
1996 and 2004. Moreover, we wanted to determine whether these attitudes were
associated with individual characteristics (age, gender, investments in work) and
whether attitudes of specialists within a partnership showed more resemblance
than specialists' attitudes from different partnerships. METHODS: Two samples
were used in this study: data of a survey conducted in 1996 and in 2004. After
selecting internal medicine specialists working in general hospitals in The
Netherlands, the sample consisted of 219 specialists in 1996 and 363 specialists
in 2004. They were sent a questionnaire, including topics on the attitudes
towards part-time work. RESULTS: Internal medicine specialists' attitudes towards
working part-time became slightly more positive between 1996 and 2004. Full-time
working specialists in 2004 still expressed concerns regarding the investments of
part-timers in overhead tasks, the flexibility of task division, efficiency,
communication and continuity of care. In 1996 gender was the only predictor of
the attitude, in 2004 being a full- or a part-timer, age and the time invested in
work were associated with this attitude. Furthermore, specialists' attitudes were
not found to cluster much within partnerships. CONCLUSION: In spite of the
increasing number of specialists working or preferring to work part-time, part
time practice among internal medicine specialists seems not to be fully accepted.
The results indicate that the attitudes are no longer gender based, but are
associated with age and work aspects such as the number of hours worked. Though
there is little evidence to support them, negative ideas about the consequences
of part-time work for the quality of care still exist. Policy should be aimed at
removing the organisational difficulties related to part-time work and create a
system in which part-time practice is fully integrated and accepted.
PMID- 17026740
TI - Clinicopathological significance of stromal variables: angiogenesis,
lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal
carcinomas.
AB - Cancer research has mainly focused on alterations of genes and proteins in cancer
cells themselves that result in either gain-of-function in oncogenes or loss-of
function in tumour-suppressor genes. However, stromal variables within or around
tumours, including blood and lymph vessels, stromal cells and various proteins,
have also important impacts on tumour development and progression. It has been
shown that disruption of stromal-epithelial interactions influences cellular
proliferation, differentiation, death, motility, genomic integrity, angiogenesis,
and other phenotypes in various tissues. Moreover, stromal variables are also
critical to therapy in cancer patients. In this review, we mainly focus on the
clinicopathological significance of stromal variables including angiogenesis,
lymphangiogenesis, inflammatory infiltration, matrix metalloproteinase (MMP), and
the particularly interesting new cysteine-histidine rich protein (PINCH) in
colorectal cancer (CRC).
PMID- 17026743
TI - Trends in scientific activity addressing transmissible spongiform
encephalopathies: a bibliometric study covering the period 1973-2002.
AB - BACKGROUND: The purpose of this study is to analyse the trends in scientific
research on transmissible spongiform encephalopathies by applying bibliometric
tools to the scientific literature published between 1973 and 2002. METHODS: The
data for the study were obtained from Medline database, in order to determine the
volume of scientific output in the above period, the countries involved, the type
of document and the trends in the subject matters addressed. The period 1973-2002
was divided in three sub-periods. RESULTS: We observed a significant growth in
scientific production. The percentage of increase is 871.7 from 1973 to 2002.
This is more evident since 1991 and particularly in the 1996-2001 period. The
countries found to have the highest output were the United States, the United
Kingdom, Japan, France and Germany. The evolution in the subject matters was
almost constant in the three sub-periods in which the study was divided. In the
first and second sub-periods, the subject matters of greatest interest were more
general, i.e Nervous system or Nervous system diseases, Creutzfeldt-Jakob
disease, Scrapie, and Chemicals and Drugs, but in the last sub-period, some
changes were observed because the Prion-related matters had the greatest
presence. Collaboration among authors is small from 1973 to 1992, but increases
notably in the third sub-period, and also the number of authors and clusters
formed. Some of the authors, like Gajdusek or Prusiner, appear in the whole
period. CONCLUSION: The study reveals a very high increase in scientific
production. It is related also with the beginnings of research on bovine
spongiform encephalopathy and variant Creutzfeldt-Jakob disease, with the
establishment of progressive collaboration relationships and a reflection of
public health concerns about this problem.
PMID- 17026744
TI - [X]uniqMAP: unique gene sequence regions in the human and mouse genomes.
AB - BACKGROUND: Current approaches for genome-wise functional analyses, such as
microarray and RNA interference studies, rely on the specificity of
oligonucleotide sequences to selectively target cellular transcripts. The design
of specific oligos involves the determination of unique DNA regions in the
gene/transcripts of interest from the targeted organism. This process is tedious,
time consuming and it does not scale up for high-throughput studies. DESCRIPTION:
Taking advantage of the availability of complete genome sequence information for
mouse and human, the most widely used systems for the study of mammalian
genetics, we have built a database, [X]uniqMAP, that stores the precalculated
unique regions for all transcripts of these two organisms. For each gene, the
database discriminates between those unique regions that are shared by all
transcripts and those exclusive to single transcripts. In addition, it also
provides those unique regions that are shared between orthologous genes from the
two organisms. The database is updated regularly to reflect changes in genome
assemblies and gene builds. CONCLUSION: Over 85% of genes have unique regions at
least 19 bases long, with the majority being unique over 60% of their lengths.
14482 human genes share exactly at least a unique region with mouse genes, though
such regions are typically under 40 bases long. The full data are publicly
accessible online both interactively and for download. They should facilitate (i)
the design of probes, primers and siRNAs for both small- and large-scale
projects; and (ii) the identification of regions for the design of oligos that
could be re-used to target equivalent gene/transcripts from human and mouse.
PMID- 17026742
TI - Hyper-IgG4 disease: report and characterisation of a new disease.
AB - BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4
disease', which has many synonyms depending on the organ involved, the country of
origin and the year of the report. It is characterized histologically by a
lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis,
which leaves dense fibrosis on resolution. A typical example is idiopathic
retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing
pancreatitis. METHODS: We report an index case with fever and severe systemic
disease. We have also reviewed the histology of 11 further patients with
idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells,
and examined a wide range of other inflammatory conditions and fibrotic diseases
as organ-specific controls. We have reviewed the published literature for disease
associations with idiopathic, systemic fibrosing conditions and the synonyms:
pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis,
xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from
all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell
infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes
eosinophilic aggregates, with venulitis and obliterative arteritis. The majority
of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell
rich small lymphoid follicles. In all cases, there was a significant increase in
IgG4-positive plasma cells compared with controls. In two cases, biopsies before
and after steroid treatment were available, and only scattered plasma cells were
seen after treatment, none of them expressing IgG4. Review of the literature
shows that although pathology commonly appears confined to one organ, patients
can have systemic symptoms and fever. In the active period, there is an acute
phase response with a high serum concentration of IgG, and during this phase,
there is a rapid clinical response to glucocorticoid steroid treatment.
CONCLUSION: We believe that hyper-IgG4 disease is an important condition to
recognise, as the diagnosis can be readily verified and the outcome with
treatment is very good.
PMID- 17026745
TI - Dog Y chromosomal DNA sequence: identification, sequencing and SNP discovery.
AB - BACKGROUND: Population genetic studies of dogs have so far mainly been based on
analysis of mitochondrial DNA, describing only the history of female dogs. To get
a picture of the male history, as well as a second independent marker, there is a
need for studies of biallelic Y-chromosome polymorphisms. However, there are no
biallelic polymorphisms reported, and only 3200 bp of non-repetitive dog Y
chromosome sequence deposited in GenBank, necessitating the identification of dog
Y chromosome sequence and the search for polymorphisms therein. The genome has
been only partially sequenced for one male dog, disallowing mapping of the
sequence into specific chromosomes. However, by comparing the male genome
sequence to the complete female dog genome sequence, candidate Y-chromosome
sequence may be identified by exclusion. RESULTS: The male dog genome sequence
was analysed by Blast search against the human genome to identify sequences with
a best match to the human Y chromosome and to the female dog genome to identify
those absent in the female genome. Candidate sequences were then tested for male
specificity by PCR of five male and five female dogs. 32 sequences from the male
genome, with a total length of 24 kbp, were identified as male specific, based on
a match to the human Y chromosome, absence in the female dog genome and male
specific PCR results. 14437 bp were then sequenced for 10 male dogs originating
from Europe, Southwest Asia, Siberia, East Asia, Africa and America. Nine
haplotypes were found, which were defined by 14 substitutions. The genetic
distance between the haplotypes indicates that they originate from at least five
wolf haplotypes. There was no obvious trend in the geographic distribution of the
haplotypes. CONCLUSION: We have identified 24159 bp of dog Y-chromosome sequence
to be used for population genetic studies. We sequenced 14437 bp in a worldwide
collection of dogs, identifying 14 SNPs for future SNP analyses, and giving a
first description of the dog Y-chromosome phylogeny.
PMID- 17026746
TI - The SNARE protein family of Leishmania major.
AB - BACKGROUND: Leishmania major is a protozoan parasite with a highly polarised cell
shape that depends upon endocytosis and exocytosis from a single area of the
plasma membrane, the flagellar pocket. SNAREs (soluble N-ethylmaleimide-sensitive
factor adaptor proteins receptors) are key components of the intracellular
vesicle-mediated transports that take place in all eukaryotic cells. They are
membrane-bound proteins that facilitate the docking and fusion of vesicles with
organelles. The recent availability of the genome sequence of L. major has
allowed us to assess the complement of SNAREs in the parasite and to investigate
their location in comparison with metazoans. RESULTS: Bioinformatic searches of
the L. major genome revealed a total of 27 SNARE domain-containing proteins that
could be classified in structural groups by phylogenetic analysis. 25 of these
possessed the expected features of functional SNAREs, whereas the other two could
represent kinetoplastid-specific proteins that might act as regulators of the
SNARE complexes. Other differences of Leishmania SNAREs were the absence of
double SNARE domain-containing and of the brevin classes of these proteins.
Members of the Qa group of Leishmania SNAREs showed differential expressions
profiles in the two main parasite forms whereas their GFP-tagging and in vivo
expression revealed localisations in the Golgi, late endosome/lysosome and near
the flagellar pocket. CONCLUSION: The early-branching eukaryote L. major
apparently possess a SNARE repertoire that equals in number the one of metazoans
such as Drosophila, showing that the machinery for vesicle fusion is well
conserved throughout the eukaryotes. However, the analysis revealed the absence
of certain types of SNAREs found in metazoans and yeast, while suggesting the
presence of original SNAREs as well as others with unusual localisation. This
study also presented the intracellular localisation of the L. major SNAREs from
the Qa group and reveals that these proteins could be useful as organelle markers
in this parasitic protozoon.
PMID- 17026747
TI - ORENZA: a web resource for studying ORphan ENZyme activities.
AB - BACKGROUND: Despite the current availability of several hundreds of thousands of
amino acid sequences, more than 36% of the enzyme activities (EC numbers) defined
by the Nomenclature Committee of the International Union of Biochemistry and
Molecular Biology (NC-IUBMB) are not associated with any amino acid sequence in
major public databases. This wide gap separating knowledge of biochemical
function and sequence information is found for nearly all classes of enzymes.
Thus, there is an urgent need to explore these sequence-less EC numbers, in order
to progressively close this gap. DESCRIPTION: We designed ORENZA, a PostgreSQL
database of ORphan ENZyme Activities, to collate information about the EC numbers
defined by the NC-IUBMB with specific emphasis on orphan enzyme activities.
Complete lists of all EC numbers and of orphan EC numbers are available and will
be periodically updated. ORENZA allows one to browse the complete list of EC
numbers or the subset associated with orphan enzymes or to query a specific EC
number, an enzyme name or a species name for those interested in particular
organisms. It is possible to search ORENZA for the different biochemical
properties of the defined enzymes, the metabolic pathways in which they
participate, the taxonomic data of the organisms whose genomes encode them, and
many other features. The association of an enzyme activity with an amino acid
sequence is clearly underlined, making it easy to identify at once the orphan
enzyme activities. Interactive publishing of suggestions by the community would
provide expert evidence for re-annotation of orphan EC numbers in public
databases. CONCLUSION: ORENZA is a Web resource designed to progressively bridge
the unwanted gap between function (enzyme activities) and sequence (dataset
present in public databases). ORENZA should increase interactions between
communities of biochemists and of genomicists. This is expected to reduce the
number of orphan enzyme activities by allocating gene sequences to the relevant
enzymes.
PMID- 17026748
TI - Management of plant species for controlling pests, by peasant farmers at Lagoa
Seca, Paraiba state, Brazil: an ethnoecological approach.
AB - Ethnoecological knowledge may be understood as spontaneous knowledge, culturally
referenced of any society's members, learned and transmitted through social
interactions and that are targeted at resolution of daily routine situations. The
traditional knowledge in small scale economy societies as well as the non
academic knowledge in urban-industrial societies might be included in this
concept. An ethnoecological approach study was performed here on people living at
the communities of Alvinho, Almeida, Cha do Marinho, Floriano, and Cha de Oiti,
all located in the municipality of Lagoa Seca, Paraiba state, Northeast Brazil.
The general objective pursued here was to study the knowledge that peasant
farmers have on management of plant species utilized for pest control. For this,
the methodological instruments employed here to investigate the ethnoecological
knowledge were: direct observation, structured and semi-structured interviews,
and tours conducted by local peasant farmers. We analyzed the data obtained under
an emic/etic view and also by comparing the local knowledge with those obtained
from the literature. The results showed that people in those communities utilize
management alternatives for controlling pests, which are mainly: (i) fallowing;
(ii) crop rotation; (iii) destruction of crop remains and fruits attacked by
pests; (iv) alternations of crops with repellent plants; and/or (v) mixed
cropping; (vi) insect's larvae covered with soil; (vii) crops irrigated
abundantly; and (viii) soil preparation. The recovery and comprehension we get
about this knowledge as well as the farmers' savoir faire, are extremely
important to the revival of ancient agricultural practices, which have been
forgotten due to advances in modern agriculture. The data obtained here showed
that a huge body of knowledge the farmers have on many forms or strategies of
management are generally compatible with scientific knowledge.
PMID- 17026749
TI - Double valve replacement for acute spontaneous left chordal rupture secondary to
chronic aortic incompetence.
AB - A 54 years old male with undiagnosed chronic calcific degenerative aortic valve
incompetence presented with acute left anterior chordae tendinae rupture
resulting in severe left heart failure and cardiogenic shock. He was successfully
treated with emergency double valve replacement using mechanical valves. The
pathogenesis of acute rupture of the anterior chordae tendinae, without any
evidence of infective endocarditis or ischemic heart disease seems to have been
attrition of the subvalvular mitral apparatus by the chronic regurgitant jet of
aortic incompetence with chronic volume overload. We review the literature with
specific focus on the occurrence of this unusual event.
PMID- 17026750
TI - Polymorphisms in GSTT1, GSTM1, NAT1 and NAT2 genes and bladder cancer risk in men
and women.
AB - BACKGROUND: Cigarette smoking is an established risk factor for bladder cancer.
Epidemiological and biological data suggest that genetic polymorphisms in
activating and detoxifying enzymes may play a role in determining an individual's
susceptibility to bladder cancer in particular when in combination with specific
environmental exposures such as cigarette smoking. N-acetyltransferase (NAT)
enzymes, NAT1 and NAT2, are involved in the activation and detoxification of
tobacco smoke constituents. Polymorphisms in these genes alter the ability of
these enzymes to metabolize carcinogens, as certain allelic combinations result
in a slow or rapid acetylation phenotype. Glutathione S-transferases (GSTs) also
detoxify tobacco smoke constituents, and polymorphisms within the GSTM1 and GSTT1
genes can result in a complete lack of enzyme activity. METHODS: We assessed the
association between common polymorphisms identified in the GSTM1, GSTT1, NAT1,
and NAT2 genes and the risk of bladder cancer in two nested case-control studies
within the Nurses' Health Study (n = 78 female cases, 234 female controls) and
the Health Professionals' Follow-up Study (n = 139 male cases, 293 male
controls). We also evaluated whether cigarette smoking modified the associations
of the genotypes and bladder cancer risk in men and women. RESULTS: Overall, we
observed no statistically significant associations between the polymorphisms and
bladder cancer risk among men and women, although given our sample size, we had
limited power to detect small to moderate effects. There was however the
suggestion of an increased risk among female ever smokers with the NAT2 slow
genotype and an increased risk in male never smokers with the GSTM1 null
genotype. CONCLUSION: In summary, these prospective results are consistent with
previous literature supporting associations between bladder cancer and the NAT2
slow acetylation and the GSTM1 null genotypes.
PMID- 17026751
TI - A super-spreading ewe infects hundreds with Q fever at a farmers' market in
Germany.
AB - BACKGROUND: In May 2003 the Soest County Health Department was informed of an
unusually large number of patients hospitalized with atypical pneumonia. METHODS:
In exploratory interviews patients mentioned having visited a farmers' market
where a sheep had lambed. Serologic testing confirmed the diagnosis of Q fever.
We asked local health departments in Germany to identify notified Q fever
patients who had visited the farmers market. To investigate risk factors for
infection we conducted a case control study (cases were Q fever patients,
controls were randomly selected Soest citizens) and a cohort study among vendors
at the market. The sheep exhibited at the market, the herd from which it
originated as well as sheep from herds held in the vicinity of Soest were tested
for Coxiella burnetii (C. burnetii). RESULTS: A total of 299 reported Q fever
cases was linked to this outbreak. The mean incubation period was 21 days, with
an interquartile range of 16-24 days. The case control study identified close
proximity to and stopping for at least a few seconds at the sheep's pen as
significant risk factors. Vendors within approximately 6 meters of the sheep's
pen were at increased risk for disease compared to those located farther away.
Wind played no significant role. The clinical attack rate of adults and children
was estimated as 20% and 3%, respectively, 25% of cases were hospitalized. The
ewe that had lambed as well as 25% of its herd tested positive for C. burnetii
antibodies. CONCLUSION: Due to its size and point source nature this outbreak
permitted assessment of fundamental, but seldom studied epidemiological
parameters. As a consequence of this outbreak, it was recommended that pregnant
sheep not be displayed in public during the 3rd trimester and to test animals in
petting zoos regularly for C. burnetii.
PMID- 17026752
TI - Evaluation of the acquired immune responses to Plasmodium vivax VIR variant
antigens in individuals living in malaria-endemic areas of Brazil.
AB - BACKGROUND: The naturally-acquired immune response to Plasmodium vivax variant
antigens (VIR) was evaluated in individuals exposed to malaria and living in
different endemic areas for malaria in the north of Brazil. METHODS: Seven
recombinant proteins representing four vir subfamilies (A, B, C, and E) obtained
from a single patient from the Amazon Region were expressed in Escherichia coli
as soluble glutathione S-transferase fusion proteins. The different recombinant
proteins were compared by ELISA with regard to the recognition by IgM, IgG, and
IgG subclass of antibodies from 200 individuals with patent infection. RESULTS:
The frequency of individuals that presented antibodies anti-VIR (IgM plus IgG)
during the infection was 49%. The frequencies of individuals that presented IgM
or IgG antibodies anti-VIR were 29.6% or 26.0%, respectively. The prevalence of
IgG antibodies against recombinant VIR proteins was significantly lower than the
prevalence of antibodies against the recombinant proteins representing two
surface antigens of merozoites of P. vivax: AMA-1 and MSP119 (57.0% and 90.5%,
respectively). The cellular immune response to VIR antigens was evaluated by in
vitro proliferative assays in mononuclear cells of the individuals recently
exposed to P. vivax. No significant proliferative response to these antigens was
observed when comparing malaria-exposed to non-exposed individuals. CONCLUSION:
This study provides evidence that there is a low frequency of individuals
responding to each VIR antigens in endemic areas of Brazil. This fact may explain
the host susceptibility to new episodes of the disease.
PMID- 17026753
TI - Ultrasound absorption and entropy production in biological tissue: a novel
approach to anticancer therapy.
AB - The entropy production of tumorous cells is higher than that of normal cells, and
entropy flow is therefore directed from tumorous toward healthy cells. This
results in information concerning the cancer propagating into the surrounding
normal tissue. However, ultrasound absorption results in additional entropy
production in tissues. The entropy mechanism possibly provides a basis for a
novel approach to anticancer therapy through the use of ultrasound irradiation.
METHODS: Through the calculation of ultrasound-induced entropy production and
comparison of the theoretical results with the experimental data on ultrasound
absorption in biological tissues, we have demonstrated that ultrasound absorption
will increase the entropy in normal tissue more efficiently than in tumorous
tissue due to the more acidic nature of the latter. Consequently, the direction
of entropy flow between these two kinds of cells may be reversed on exposure to
ultrasound. CONCLUSION: The higher entropy accumulation of normal cells during
ultrasound irradiation may possibly lead to a change in the original direction of
entropy flow and avoid the propagation of information on the cancer into the
normal tissues. We suggest that low-intensity, low-frequency ultrasound
irradiation may be an efficient tool for the therapy of solid tumors.
PMID- 17026754
TI - Oxygen limitation modulates pH regulation of catabolism and hydrogenases,
multidrug transporters, and envelope composition in Escherichia coli K-12.
AB - BACKGROUND: In Escherichia coli, pH regulates genes for amino-acid and sugar
catabolism, electron transport, oxidative stress, periplasmic and envelope
proteins. Many pH-dependent genes are co-regulated by anaerobiosis, but the
overall intersection of pH stress and oxygen limitation has not been
investigated. RESULTS: The pH dependence of gene expression was analyzed in
oxygen-limited cultures of E. coli K-12 strain W3110. E. coli K-12 strain W3110
was cultured in closed tubes containing LBK broth buffered at pH 5.7, pH 7.0, and
pH 8.5. Affymetrix array hybridization revealed pH-dependent expression of 1,384
genes and 610 intergenic regions. A core group of 251 genes showed pH responses
similar to those in a previous study of cultures grown with aeration. The highly
acid-induced gene yagU was shown to be required for extreme-acid resistance
(survival at pH 2). Acid also up-regulated fimbriae (fimAC), periplasmic
chaperones (hdeAB), cyclopropane fatty acid synthase (cfa), and the
"constitutive" Na+/H+ antiporter (nhaB). Base up-regulated core genes for
maltodextrin transport (lamB, mal), ATP synthase (atp), and DNA repair (recA,
mutL). Other genes showed opposite pH responses with or without aeration, for
example ETS components (cyo,nuo, sdh) and hydrogenases (hya, hyb, hyc, hyf, hyp).
A hypF strain lacking all hydrogenase activity showed loss of extreme-acid
resistance. Under oxygen limitation only, acid down-regulated ribosome synthesis
(rpl,rpm, rps). Acid up-regulated the catabolism of sugar derivatives whose
fermentation minimized acid production (gnd, gnt, srl), and also a cluster of 13
genes in the gadA region. Acid up-regulated drug transporters (mdtEF, mdtL), but
down-regulated penicillin-binding proteins (dacACD, mreBC). Intergenic regions
containing regulatory sRNAs were up-regulated by acid (ryeA, csrB, gadY, rybC).
CONCLUSION: pH regulates a core set of genes independently of oxygen, including
yagU, fimbriae, periplasmic chaperones, and nhaB. Under oxygen limitation,
however, pH regulation is reversed for genes encoding electron transport
components and hydrogenases. Extreme-acid resistance requires yagU and
hydrogenase production. Ribosome synthesis is down-regulated at low pH under
oxygen limitation, possibly due to the restricted energy yield of catabolism.
Under oxygen limitation, pH regulates metabolism and transport so as to maximize
alternative catabolic options while minimizing acidification or alkalinization of
the cytoplasm.
PMID- 17026755
TI - Intensive care unit-acquired Stenotrophomonas maltophilia: incidence, risk
factors, and outcome.
AB - INTRODUCTION: The aim of this study was to determine incidence, risk factors, and
impact on outcome of intensive care unit (ICU)-acquired Stenotrophomonas
maltophilia. METHODS: This prospective observational case-control study, which
was a part of a cohort study, was conducted in a 30-bed ICU during a three year
period. All immunocompetent patients hospitalised >48 hours were eligible.
Patients with non-fermenting Gram-negative bacilli (NF-GNB) at ICU admission were
excluded. Patients without ICU-acquired S. maltophilia who developed an ICU
acquired NF-GNB other than S. maltophilia were also excluded. Screening (tracheal
aspirate and skin, anal, and nasal swabs) for NF-GNB was performed in all
patients at ICU admission and weekly. Univariate and multivariate analyses were
performed to determine risk factors for ICU-acquired S. maltophilia and for ICU
mortality. RESULTS: Thirty-eight (2%) patients developed an S. maltophilia ICU
acquired colonisation and/or infection and were all successfully matched with 76
controls. Chronic obstructive pulmonary disease (COPD) and duration of antibiotic
treatment (odds ratio [OR] [95% confidence interval (CI)] = 9.4 [3 to 29], p <
0.001, and 1.4 [1 to 2.3], p = 0.001, respectively) were independently associated
with ICU-acquired S. maltophilia. Mortality rate (60% versus 40%, OR [95% CI] =
1.3 [1 to 1.7, p = 0.037]), duration of mechanical ventilation (23 +/- 16 versus
7 +/- 11 days, p < 0.001), and duration of ICU stay (29 +/- 21 versus 15 +/- 17
days, p < 0.001) were significantly higher in cases than in controls. In
addition, ICU-acquired infection related to S. maltophilia was independently
associated with ICU mortality (OR [95% CI] = 2.8 [1 to 7.7], p = 0.044).
CONCLUSION: COPD and duration of antibiotic treatment are independent risk
factors for ICU-acquired S. maltophilia. ICU-acquired S. maltophilia is
associated with increased morbidity and mortality rates. ICU-acquired infection
related to S. maltophilia is an independent risk factor for ICU mortality.
PMID- 17026756
TI - Selection of housekeeping genes for gene expression studies in human
reticulocytes using real-time PCR.
AB - BACKGROUND: Control genes, which are often referred to as housekeeping genes, are
frequently used to normalise mRNA levels between different samples. However, the
expression level of these genes may vary among tissues or cells and may change
under certain circumstances. Thus, the selection of housekeeping genes is
critical for gene expression studies. To address this issue, 7 candidate
housekeeping genes including several commonly used ones were investigated in
isolated human reticulocytes. For this, a simple DeltaCt approach was employed by
comparing relative expression of 'pairs of genes' within each sample. On this
basis, stability of the candidate housekeeping genes was ranked according to
repeatability of the gene expression differences among 31 samples. RESULTS:
Initial screening of the expression pattern demonstrated that 1 of the 7 genes
was expressed at very low levels in reticulocytes and was excluded from further
analysis. The range of expression stability of the other 6 genes was (from most
stable to least stable): GAPDH (glyceraldehyde 3-phosphate dehydrogenase), SDHA
(succinate dehydrogenase), HPRT1 (hypoxanthine phosphoribosyl transferase 1),
HBS1L (HBS1-like protein) and AHSP (alpha haemoglobin stabilising protein),
followed by B2M (beta-2-microglobulin). CONCLUSION: Using this simple approach,
GAPDH was found to be the most suitable housekeeping gene for expression studies
in reticulocytes while the commonly used B2M should be avoided.
PMID- 17026757
TI - Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like
effects, in modulating the aquaporin-9 expression in the rat efferent ductules.
AB - BACKGROUND: Fluid homeostasis is critical for normal function of the male
reproductive tract and aquaporins (AQP) play an important role in maintenance of
this water and ion balance. Several AQPs have been identified in the male, but
their regulation is not fully comprehended. Hormonal regulation of AQPs appears
to be dependent on the steroid in the reproductive tract region. AQP9 displays
unique hormonal regulation in the efferent ductules and epididymis, as it is
regulated by both estrogen and dihydrotestosterone (DHT) in the efferent
ductules, but only by DHT in the initial segment epididymis. Recent data have
shown that a metabolite of DHT, 5-alpha-androstane-3-beta-17-beta-diol (3-beta
diol), once considered inactive, is also present in high concentrations in the
male and indeed has biological activity. 3-beta-diol does not bind to the
androgen receptor, but rather to estrogen receptors ER-alpha and ER-beta, with
higher affinity for ER-beta. The existence of this estrogenic DHT metabolite has
raised the possibility that estradiol may not be the only estrogen to play a
major role in the male reproductive system. Considering that both ER-alpha and ER
beta are highly expressed in efferent ductules, we hypothesized that the DHT
regulation of AQP9 could be due to the 3-beta-diol metabolite. METHODS: To test
this hypothesis, adult male rats were submitted to surgical castration followed
by estradiol, DHT or 3-beta-diol replacement. Changes in AQP9 expression in the
efferent ductules were investigated by using immunohistochemistry and Western
blotting assay. RESULTS: Data show that, after castration, AQP9 expression was
significantly reduced in the efferent ductules. 3-beta-diol injections restored
AQP9 expression, similar to DHT and estradiol. The results were confirmed by
Western blotting assay. CONCLUSION: This is the first evidence that 3-beta-diol
has biological activity in the male reproductive tract and that this androgen
metabolite has estrogen-like activity in the efferent ductules, whose major
function is the reabsorption of luminal fluid.
PMID- 17026758
TI - Inhibition of prefrontal protein synthesis following recall does not disrupt
memory for trace fear conditioning.
AB - BACKGROUND: The extent of similarity between consolidation and reconsolidation is
not yet fully understood. One of the differences noted is that not every brain
region involved in consolidation exhibits reconsolidation. In trace fear
conditioning, the hippocampus and the medial prefrontal cortex (mPFC) are
required for consolidation of long-term memory. We have previously demonstrated
that trace fear memory is susceptible to infusion of the protein synthesis
inhibitor anisomycin into the hippocampus following recall. In the present study,
we examine whether protein synthesis inhibition in the mPFC following recall
similarly results in the observation of reconsolidation of trace fear memory.
RESULTS: Targeted intra-mPFC infusions of anisomycin or vehicle were performed
immediately following recall of trace fear memory at 24 hours, or at 30 days,
following training in a one-day or a two-day protocol. The present study
demonstrates three key findings: 1) trace fear memory does not undergo protein
synthesis dependent reconsolidation in the PFC, regardless of the intensity of
the training, and 2) regardless of whether the memory is recent or remote, and 3)
intra-mPFC inhibition of protein synthesis immediately following training
impaired remote (30 days) memory. CONCLUSION: These results suggest that not all
structures that participate in memory storage are involved in reconsolidation.
Alternatively, certain types of memory-related information may reconsolidate,
while other components of memory may not.
PMID- 17026760
TI - Breast carcinoma and malignant melanoma metastasis within a single axillary lymph
node.
AB - A 58 year old lady presented with a right breast cancer and a prior history of
malignant melanoma excised from the right chest wall eight years previously. An
abnormal axillary lymph node resected contained features of both metastatic
breast carcinoma and malignant melanoma. Following oncologic breast cancer
management, the patient is well with no evidence of recurrence at three years.
PMID- 17026759
TI - Breast cancer risk and drinking water contaminated by wastewater: a case control
study.
AB - BACKGROUND: Drinking water contaminated by wastewater is a potential source of
exposure to mammary carcinogens and endocrine disrupting compounds from
commercial products and excreted natural and pharmaceutical hormones. These
contaminants are hypothesized to increase breast cancer risk. Cape Cod,
Massachusetts, has a history of wastewater contamination in many, but not all, of
its public water supplies; and the region has a history of higher breast cancer
incidence that is unexplained by the population's age, in-migration, mammography
use, or established breast cancer risk factors. We conducted a case-control study
to investigate whether exposure to drinking water contaminated by wastewater
increases the risk of breast cancer. METHODS: Participants were 824 Cape Cod
women diagnosed with breast cancer in 1988-1995 and 745 controls who lived in
homes served by public drinking water supplies and never lived in a home served
by a Cape Cod private well. We assessed each woman's exposure yearly since 1972
at each of her Cape Cod addresses, using nitrate nitrogen (nitrate-N) levels
measured in public wells and pumping volumes for the wells. Nitrate-N is an
established wastewater indicator in the region. As an alternative drinking water
quality indicator, we calculated the fraction of recharge zones in residential,
commercial, and pesticide land use areas. RESULTS: After controlling for
established breast cancer risk factors, mammography, and length of residence on
Cape Cod, results showed no consistent association between breast cancer and
average annual nitrate-N (OR = 1.8; 95% CI 0.6-5.0 for > or = 1.2 vs. < .3 mg/L),
the sum of annual nitrate-N concentrations (OR = 0.9; 95% CI 0.6-1.5 for > or =
10 vs. 1 to < 10 mg/L), or the number of years exposed to nitrate-N over 1 mg/L
(OR = 0.9; 95% CI 0.5-1.5 for > or = 8 vs. 0 years). Variation in exposure levels
was limited, with 99% of women receiving some of their water from supplies with
nitrate-N levels in excess of background. The total fraction of residential,
commercial, and pesticide use land in recharge zones of public supply wells was
associated with a small statistically unstable higher breast cancer incidence (OR
= 1.4; 95% CI 0.8-2.4 for highest compared with lowest land use), but risk did
not increase for increasing land use fractions. CONCLUSION: Results did not
provide evidence of an association between breast cancer and drinking water
contaminated by wastewater. The computer mapping methods used in this study to
link routine measurements required by the Safe Drinking Water Act with interview
data can enhance individual-level epidemiologic studies of multiple health
outcomes, including diseases with substantial latency.
PMID- 17026761
TI - Priority setting in developing countries health care institutions: the case of a
Ugandan hospital.
AB - BACKGROUND: Because the demand for health services outstrips the available
resources, priority setting is one of the most difficult issues faced by health
policy makers, particularly those in developing countries. However, there is lack
of literature that describes and evaluates priority setting in these contexts.
The objective of this paper is to describe priority setting in a teaching
hospital in Uganda and evaluate the description against an ethical framework for
fair priority setting processes--Accountability for Reasonableness. METHODS: A
case study in a 1,500 bed national referral hospital receiving 1,320 out patients
per day and an average budget of 13.5 million US dollars per year. We reviewed
documents and carried out 70 in-depth interviews (14 health planners, 40 doctors,
and 16 nurses working at the hospital). Interviews were recorded and transcribed.
Data analysis employed the modified thematic approach to describe priority
setting, and the description was evaluated using the four conditions of
Accountability for Reasonableness: relevance, publicity, revisions and
enforcement. RESULTS: Senior managers, guided by the hospital strategic plan make
the hospital budget allocation decisions. Frontline practitioners expressed lack
of knowledge of the process. RELEVANCE: Priority is given according to a cluster
of factors including need, emergencies and patient volume. However, surgical
departments and departments whose leaders "make a lot of noise" are also
prioritized. Publicity: Decisions, but not reasons, are publicized through
general meetings and circulars, but this information does not always reach the
frontline practitioners. Publicity to the general public was through ad hoc radio
programs and to patients who directly ask. Revisions: There were no formal
mechanisms for challenging the reasoning. Enforcement: There were no mechanisms
to ensure adherence to the four conditions of a fair process. CONCLUSION:
Priority setting decisions at this hospital do not satisfy the conditions of
fairness. To improve, the hospital should: (i) engage frontline practitioners,
(ii) publicize the reasons for decisions both within the hospital and to the
general public, and (iii) develop formal mechanisms for challenging the
reasoning. In addition, capacity strengthening is required for senior managers
who must accept responsibility for ensuring that the above three conditions are
met.
PMID- 17026762
TI - The difficult doctor? Characteristics of physicians who report frustration with
patients: an analysis of survey data.
AB - BACKGROUND: Literature on difficult doctor-patient relationships has focused on
the "difficult patient." Our objective was to determine physician and practice
characteristics associated with greater physician-reported frustration with
patients. METHODS: We conducted a secondary analysis of the Physicians Worklife
Survey, which surveyed a random national sample of physicians. Participants were
1391 family medicine, general internal medicine, and medicine subspecialty
physicians. The survey assessed physician and practice characteristics, including
stress, depression and anxiety symptoms, practice setting, work hours, case-mix,
and control over administrative and clinical practice. Physicians estimated the
percentage of their patients who were "generally frustrating to deal with." We
categorized physicians by quartile of reported frustrating patients and compared
characteristics of physicians in the top quartile to those in the other three
quartiles. We used logistic regression to model physician characteristics
associated with greater frustration. RESULTS: In unadjusted analyses, physicians
who reported high frustration with patients were younger (p < 0.001); worked more
hours per week (p = 0.041); and had more symptoms of depression, stress, and
anxiety (p < 0.004 for all). In the final model, factors independently associated
with high frustration included age < 40 years, work hours > 55 per week, higher
stress, practice in a medicine subspeciality, and greater number of patients with
psychosocial problems or substance abuse. CONCLUSION: Personal and practice
characteristics of physicians who report high frustration with patients differ
from those of other physicians. Understanding factors contributing to physician
frustration with patients may allow us to improve the quality of patient
physician relationships.
PMID- 17026763
TI - Validation of the Provincial Transfer Authorization Centre database: a
comprehensive database containing records of all inter-facility patient transfers
in the province of Ontario.
AB - BACKGROUND: The Provincial Transfer Authorization Centre (PTAC) was established
as a part of the emergency response in Ontario, Canada to the Severe Acute
Respiratory Syndrome (SARS) outbreak in 2003. Prior to 2003, data relating to
inter-facility patient transfers were not collected in a systematic manner. Then,
in an emergency setting, a comprehensive database with a complex data collection
process was established. For the first time in Ontario, population-based data for
patient movement between healthcare facilities for a population of twelve million
are available. The PTAC database stores all patient transfer data in a large
database. There are few population-based patient transfer databases and the PTAC
database is believed to be the largest example to house this novel dataset. A
patient transfer database has also never been validated. This paper presents the
validation of the PTAC database. METHODS: A random sample of 100 patient inter
facility transfer records was compared to the corresponding institutional patient
records from the sending healthcare facilities. Measures of agreement, including
sensitivity, were calculated for the 12 common data variables. RESULTS: Of the
100 randomly selected patient transfer records, 95 (95%) of the corresponding
institutional patient records were located. Data variables in the categories
patient demographics, facility identification and timing of transfer and reason
and urgency of transfer had strong agreement levels. The 10 most commonly used
data variables had accuracy rates that ranged from 85.3% to 100% and error rates
ranging from 0 to 12.6%. These same variables had sensitivity values ranging from
0.87 to 1.0. CONCLUSION: The very high level of agreement between institutional
patient records and the PTAC data for fields compared in this study supports the
validity of the PTAC database. For the first time, a population-based patient
transfer database has been established. Although it was created during an
emergency situation and data collection is dependent on front-line medical
workers, the PTAC data has achieved a high level of validity, perhaps even higher
than many purpose built databases created during non-emergency settings.
PMID- 17026764
TI - In the absence of cancer registry data, is it sensible to assess incidence using
hospital separation records?
AB - BACKGROUND: Within the health literature, a major goal is to understand
distribution of service utilisation by social location. Given equivalent access,
differential incidence leads to an expectation of differential service
utilisation. Cancer incidence is differentially distributed with respect to
socioeconomic status. However, not all jurisdictions have incidence registries,
and not all registries allow linkage with utilisation records. The British
Columbia Linked Health Data resource allows such linkage. Consequently, we
examine whether, in the absence of registry data, first hospitalisation can act
as a proxy measure for incidence, and therefore as a measure of need for service.
METHODS: Data are drawn from the British Columbia Linked Health Data resource,
and represent 100% of Vancouver Island Health Authority cancer registry and
hospital records, 1990-1999. Hospital separations (discharges) with principal
diagnosis ICD-9 codes 140-208 are included, as are registry records with ICDO-2
codes C00-C97. Non-melanoma skin cancer (173/C44) is excluded. Lung, colorectal,
female breast, and prostate cancers are examined separately. We compare registry
and hospital annual counts and age-sex distributions, and whether the same
individuals are represented in both datasets. Sensitivity, specificity and
predictive values are calculated, as is the kappa statistic for agreement. The
registry is designated the gold standard. RESULTS: For all cancers combined,
first hospitalisation counts consistently overestimate registry incidence counts.
From 1995-1999, there is no significant difference between registry and hospital
counts for lung and colorectal cancer (p = 0.42 and p = 0.56, respectively). Age
sex distribution does not differ for colorectal cancer. Ten-year period
sensitivity ranges from 73.0% for prostate cancer to 84.2% for colorectal cancer;
ten-year positive predictive values range from 89.5% for female breast cancer to
79.35% for prostate cancer. Kappa values are consistently high. CONCLUSION:
Claims and registry databases overlap with an appreciable proportion of the same
individuals. First hospital separation may be considered a proxy for incidence
with reference to colorectal cancer since 1995. However, to examine equity across
cancer health services utilisation, it is optimal to have access to both hospital
and registry files.
PMID- 17026765
TI - Tumor suppressor gene methylation in follicular lymphoma: a comprehensive review.
AB - Transcriptional silencing of tumor suppressor genes, associated with DNA
methylation, is a common epigenetic event in hematologic malignancies. Although
DNA hypermethylation of CpG islands is well described in acute leukemias and
myelodysplastic syndromes, much less is known of the specific methylation changes
that commonly occur in follicular B cell lymphomas. Earlier methylation studies
of follicular lymphoma involved only cell lines; however there is a growing
literature of methylation changes in primary human FL samples. Published studies
of primary follicular lymphoma specimens have demonstrated that: androgen
receptor, SHP1, and death-associated protein kinase genes are commonly
methylated. By contrast, the cyclin dependent kinase inhibitors p15, p16, and p57
are uncommon epigenetic events in follicular lymphoma. Methylation of cyclin
dependent kinase inhibitors is more common in high grade lymphomas, and may be an
important step in the progression and transformation of follicular lymphoma.
Further methylation studies in follicular lymphoma should investigate the
prognostic and therapeutic significance of these epigenetic changes and
investigate methylation of other genes. Finally, reactivation of methylated tumor
suppressor genes through the use of hypomethylating agents is a promising and
novel approach to the treatment of indolent and transformed follicular lymphomas.
PMID- 17026766
TI - Anticipating pulmonary complications after thoracotomy: the FLAM Score.
AB - OBJECTIVE: Pulmonary complications after thoracotomy are the result of
progressive changes in the respiratory status of the patient. A multifactorial
score (FLAM score) was developed to identify postoperatively patients at higher
risk for pulmonary complications at least 24 hours before the clinical diagnosis.
METHODS: The FLAM score, created in 2002, is based on 7 parameters (dyspnea,
chest X-ray, delivered oxygen, auscultation, cough, quality and quantity of
bronchial secretions). To validate the FLAM score, we prospectively calculated
scores during the first postoperative week in 300 consecutive patients submitted
to posterolateral thoracotomy. RESULTS: During the study, 60 patients (20%)
developed pulmonary complications during the postoperative period. The FLAM score
progressively increased in complicated patients until the fourth postoperative
day (mean 13.5 +/- 11.9). FLAM scores in patients with complications were
significantly higher (p < 0.05) at least 24 hours before the clinical diagnosis
of complication, compared to FLAM scores in uncomplicated patients. ROC curves
analysis showed that the cut-off value of FLAM with the best sensitivity and
specificity for pulmonary complications was 9 (area under the curve 0.97). Based
on the highest FLAM scores recorded, 4 risk classes were identified with
increasing incidence of pulmonary complications and mortality. CONCLUSION:
Changes in FLAM score were evident at least 24 hours before the clinical
diagnosis of pulmonary complications.FLAM score can be used to categorize
patients according to risk of respiratory morbidity and mortality and could be a
useful tool in the postoperative management of patients undergoing thoracotomy.
PMID- 17026767
TI - Insights into the evolution of the ErbB receptor family and their ligands from
sequence analysis.
AB - BACKGROUND: In the time since we presented the first molecular evolutionary study
of the ErbB family of receptors and the EGF family of ligands, there has been a
dramatic increase in genomic sequences available. We have utilized this greatly
expanded data set in this study of the ErbB family of receptors and their
ligands. RESULTS: In our previous analysis we postulated that EGF family ligands
could be characterized by the presence of a splice site in the coding region
between the fourth and fifth cysteines of the EGF module and the placement of
that module near the transmembrane domain. The recent identification of several
new ligands for the ErbB receptors supports this characterization of an ErbB
ligand; further, applying this characterization to available sequences suggests
additional potential ligands for these receptors, the EGF modules from previously
identified proteins: interphotoreceptor matrix proteoglycan-2, the alpha and beta
subunit of meprin A, and mucins 3, 4, 12, and 17. The newly available sequences
have caused some reorganizations of relationships among the ErbB ligand family,
but they add support to the previous conclusion that three gene duplication
events gave rise to the present family of four ErbB receptors among the
tetrapods. CONCLUSION: This study provides strong support for the hypothesis that
the presence of an easily identifiable sequence motif can distinguish EGF family
ligands from other EGF-like modules and reveals several potential new EGF family
ligands. It also raises interesting questions about the evolution of ErbB2 and
ErbB3: Does ErbB2 in teleosts function differently from ErbB2 in tetrapods in
terms of ligand binding and intramolecular tethering? When did ErbB3 lose kinase
activity, and what is the functional significance of the divergence of its kinase
domain among teleosts?
PMID- 17026768
TI - Use of selected complementary and alternative medicine (CAM) treatments in
veterans with cancer or chronic pain: a cross-sectional survey.
AB - BACKGROUND: Complementary and alternative medicine (CAM) is emerging as an
important form of care in the United States. We sought to measure the prevalence
of selected CAM use among veterans attending oncology and chronic pain clinics
and to describe the characteristics of CAM use in this population. METHODS: The
self-administered, mail-in survey included questions on demographics, health
beliefs, medical problems and 6 common CAM treatments (herbs, dietary
supplements, chiropractic care, massage therapy, acupuncture and homeopathy) use.
We used the chi-square test to examine bivariate associations between our
predictor variables and CAM use. RESULTS: Seventy-two patients (27.3%) reported
CAM use within the past 12 months. CAM use was associated with more education (p
= 0.02), higher income (p = 0.006), non-VA insurance (p = 0.003), additional care
outside the VA (p = 0.01) and the belief that lifestyle contributes to illness (p
= 0.015). The diagnosis of chronic pain versus cancer was not associated with
differential CAM use (p = 0.15). Seventy-six percent of CAM non-users reported
that they would use it if offered at the VA. CONCLUSION: Use of 6 common CAM
treatments among these veterans is lower than among the general population, but
still substantial. A large majority of veterans reported interest in using CAM
modalities if they were offered at the VA. A national assessment of veteran
interest in CAM may assist VA leaders to respond to patients' needs.
PMID- 17026769
TI - Medicinal plants used by traditional healers in Kancheepuram district of Tamil
Nadu, India.
AB - An ethnobotanical survey was undertaken to collect information from traditional
healers on the use of medicinal plants in Kancheepuram district of Tamil Nadu
during October 2003 to April 2004. The indigenous knowledge of local traditional
healers and the native plants used for medicinal purposes were collected through
questionnaire and personal interviews during field trips.The investigation
revealed that, the traditional healers used 85 species of plants distributed in
76 genera belonging to 41 families to treat various diseases. The documented
medicinal plants were mostly used to cure skin diseases, poison bites,
stomachache and nervous disorders. In this study the most dominant family was
Euphorbiaceae and leaves were most frequently used for the treatment of
diseases.This study showed that many people in the studied parts of Kancheepuram
district still continue to depend on medicinal plants at least for the treatment
of primary healthcare. The traditional healers are dwindling in number and there
is a grave danger of traditional knowledge disappearing soon since the younger
generation is not interested to carry on this tradition.
PMID- 17026770
TI - Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease.
AB - Secretory phospholipase A2-IIA (sPLA2-IIA) is an inflammatory protein known to
play a role in the pathogenesis of many inflammatory diseases. Although this
enzyme has also been implicated in the pathogenesis of neurodegenerative
diseases, there has not been a direct demonstration of its expression in diseased
human brain. In this study, we show that sPLA2-IIA mRNA is up-regulated in
Alzheimer's disease (AD) brains as compared to non-demented elderly brains (ND).
We also report a higher percentage of sPLA2-IIA-immunoreactive astrocytes present
in AD hippocampus and inferior temporal gyrus (ITG). In ITG, the majority of
sPLA2-IIA-positive astrocytes were associated with amyloid beta (Abeta)
containing plaques. Studies with human astrocytes in culture demonstrated the
ability of oligomeric Abeta1-42 and interleukin-1beta (IL-1beta) to induce sPLA2
IIA mRNA expression, indicating that this gene is among those induced by
inflammatory cytokines. Since exogenous sPLA2-IIA has been shown to cause
neuronal injury, understanding the mechanism(s) and physiological consequences of
sPLA2-IIA upregulation in AD brain may facilitate the development of novel
therapeutic strategies to inhibit the inflammatory responses and to retard the
progression of the disease.
PMID- 17026772
TI - Malignant potential of intrahepatic biliary papillomatosis: a case report and
review of the literature.
AB - BACKGROUND: Biliary papillomatosis (BP) is a rare disease entity with a strong
malignant potential. It is characterized by multiple papillary adenomas involving
both the intrahepatic and extrahepatic biliary tree. BP was considered in the
past to be a disease with low malignant potential. However, a current review of
the English literature revealed a high rate of malignant occurrence of
approximately 41% and histological analysis along with the expression pattern of
mucin core proteins (MUC) and mucin carbohydrate antigens suggests that BP is a
borderline or low grade malignant neoplasm with a high malignant potential. CASE
PRESENTATION: A 68 year-old male patient was referred to our hospital due to the
presence of sudden right upper quadrant abdominal pain, nausea and dark urine.
Imaging workup demonstrated dilatation of the left hepatic duct without the
presence of a space-occupying lesion. A left hepatectomy and cholecystectomy were
carried out and histological analysis revealed a moderately to poorly
differentiated carcinoma of the left hepatic duct in the background of biliary
papillomatosis. Postoperative course was uneventful. Unfortunately, two years
after initial diagnosis the patient rapidly deteriorated and died from multiple
pulmonary secondary deposits. CONCLUSION: BP should not be considered to be a
benign disease. The clinical behavior, the high recurrence rate and the even
higher malignant transformation occurrence, as well as the presence of
carcinogenetic indicators (K-ras mutation, overexpression of p53, MUC and Tn
antigens) strongly support that BP is a low-grade neoplasm with high malignant
potential.
PMID- 17026771
TI - Finasteride induced depression: a prospective study.
AB - BACKGROUND: Finasteride is a competitive inhibitor of 5 alpha-reductase enzyme,
and is used for treatment of benign prostatic hyperplasia and androgenetic
alopecia. Animal studies have shown that finasteride might induce behavioral
changes. Additionally, some cases of finasteride-induced depression have been
reported in humans. The purpose of this study was to examine whether depressive
symptoms or anxiety might be induced by finasteride administration. METHODS: One
hundred and twenty eight men with androgenetic alopecia, who were prescribed
finasteride (1 mg/day) were enrolled in this study. Information on depressed mood
and anxiety was obtained by Beck Depression Inventory (BDI), and Hospital Anxiety
and Depression Scale (HADS). Participants completed BDI and HADS questionnaires
before beginning the treatment and also two months after it. RESULTS: Mean age of
the subjects was 25.8(+/- 4.4) years. At baseline, mean BDI and HADS depression
scores were 12.11(+/- 7.50) and 4.04(+/- 2.51), respectively. Finasteride
treatment increased both BDI (p < 0.001) and HADS depression scores significantly
(p = 0.005). HADS anxiety scores were increased, but the difference was not
significant (p = 0.061). CONCLUSION: This preliminary study suggests that
finasteride might induce depressive symptoms; therefore this medication should be
prescribed cautiously for patients with high risk of depression. It seems that
further studies would be necessary to determine behavioral effects of this
medication in higher doses and in more susceptible patients.
PMID- 17026773
TI - Methylene blue for malaria in Africa: results from a dose-finding study in
combination with chloroquine.
AB - The development of safe, effective and affordable drug combinations against
malaria in Africa is a public health priority. Methylene blue (MB) has a similar
mode of action as chloroquine (CQ) and has moreover been shown to selectively
inhibit the Plasmodium falciparum glutathione reductase. In 2004, an uncontrolled
dose-finding study on the combination MB-CQ was performed in 435 young children
with uncomplicated falciparum malaria in Burkina Faso (CQ monotherapy had a > 50%
clinical failure rate in this area in 2003). Three serious adverse events (SAE)
occurred of which one was probably attributable to the study medication. In the
per protocol safety analysis, there were no dose specific effects. The overall
clinical and parasitological failure rates by day 14 were 10% [95% CI (7.5%,
14.0%)] and 24% [95% CI (19.4%, 28.3%)], respectively. MB appears to have
efficacy against malaria, but the combination of CQ-MB is clearly not effective
in the treatment of malaria in Africa.
PMID- 17026774
TI - Abdominal wall implantation of hepatocellular carcinoma.
AB - BACKGROUND: Percutaneous fine needle aspiration cytology (FNAC) became a popular
method for diagnosis of hepatic masses. Abdominal wall implantation from FNAC is
rare. CASE PRESENTATION: We report a female patient who presented with a right
upper abdominal wall mass 3 years following a fine needle aspiration cytology
(FNAC) and resection of a solitary hepatocellular carcinoma (HCC) from the liver.
The mass proved to be a metastatic HCC; it was locally resected with safety
margins. To date (20 months later) she remains well with no recurrence.
CONCLUSION: Implantation of tumor cells after FNAC for HCC is rare, but can
happen. The availability of dynamic imaging of the liver should reduce the need
for this technique in the diagnostic workup of patients suspected of having HCC.
PMID- 17026775
TI - STAR: predicting recombination sites from amino acid sequence.
AB - BACKGROUND: Designing novel proteins with site-directed recombination has
enormous prospects. By locating effective recombination sites for swapping
sequence parts, the probability that hybrid sequences have the desired properties
is increased dramatically. The prohibitive requirements for applying current
tools led us to investigate machine learning to assist in finding useful
recombination sites from amino acid sequence alone. RESULTS: We present STAR,
Site Targeted Amino acid Recombination predictor, which produces a score
indicating the structural disruption caused by recombination, for each position
in an amino acid sequence. Example predictions contrasted with those of
alternative tools, illustrate STAR'S utility to assist in determining useful
recombination sites. Overall, the correlation coefficient between the output of
the experimentally validated protein design algorithm SCHEMA and the prediction
of STAR is very high (0.89). CONCLUSION: STAR allows the user to explore useful
recombination sites in amino acid sequences with unknown structure and unknown
evolutionary origin. The predictor service is available from
http://pprowler.itee.uq.edu.au/star.
PMID- 17026777
TI - Development of a new set of reference genes for normalization of real-time RT-PCR
data of porcine backfat and longissimus dorsi muscle, and evaluation with
PPARGC1A.
AB - BACKGROUND: An essential part of using real-time RT-PCR is that expression
results have to be normalized before any conclusions can be drawn. This can be
done by using one or multiple, validated reference genes, depending on the
desired accuracy of the results. In the pig however, very little information is
available on the expression stability of reference genes. The aim of this study
was therefore to develop a new set of reference genes which can be used for
normalization of mRNA expression data of genes expressed in porcine backfat and
longissimus dorsi muscle, both representing an economically important part of a
pig's carcass. Because of its multiple functions in fat metabolism and muscle
fibre type composition, peroxisome proliferative activated receptor gamma
coactivator 1alpha (PPARGC1A) is a very interesting candidate gene for meat
quality, and was an ideal gene to evaluate our developed set of reference genes
for normalization of mRNA expression data of both tissue types. RESULTS: The mRNA
expression stability of 10 reference genes was determined. The expression of
RPL13A and SDHA appeared to be highly unstable. After normalization to the
geometric mean of the three most stably expressed reference genes (ACTB, TBP and
TOP2B), the results not only showed that the mRNA expression of PPARGC1A was
significantly higher in each of the longissimus dorsi muscle samples than in
backfat (P < 0.05), but also that the expression was significantly higher in the
most cranial of the three muscle samples (P < 0.05). CONCLUSION: This study
provides a new set of reference genes (ACTB, TBP and TOP2B) suitable for
normalization of real-time RT-PCR data of backfat and longissimus dorsi muscle in
the pig. The obtained PPARGC1A expression results, after application of this set
of reference genes, are a first step in unravelling the PPARGC1A expression
pattern in the pig and provide a basis for possible selection towards improved
meat quality while maintaining a lean carcass.
PMID- 17026778
TI - An estimate of the prevalence of dementia among residents of long-term care
geriatric institutions in the Jerusalem area.
AB - BACKGROUND: To determine the prevalence of dementia among the residents of
geriatric institutions in the greater Jerusalem area. METHODS: A population
based, cross-sectional survey of a representative sample, weighted according to
the level of care, of 11 of the 88 long-term care (LTC) wards in 34 LTC
institutions providing care for the elderly residents in the greater Jerusalem
area in 1999. A single physician interviewed 311 residents. The presence of
dementia was determined from medical records and by performance on the Modified
Mini-mental State Examination (3MS) instrument (with a score less than 78/100
indicating significant cognitive impairment or suspected dementia), and
professional care providers were interviewed for their opinion regarding the
presence of dementia in each subject. RESULTS: The mean age of the patients was
83.9 years and 75% were women. Overall, 180 residents, representing 49.9% of the
weighted sample in Jerusalem LTC facilities, were determined to have dementia
according to medical records, ranging from 22.9% in independent and frail care
units to 97.7% in skilled nursing care wards. However, based on their performance
on the 3MS, the prevalence of cognitive impairment with suspected dementia among
the subjects was substantially greater, with the staff being unaware of this
diagnosis in about one-quarter of the subjects. CONCLUSIONS: There is a high
prevalence of dementia in geriatric institutions in the Jerusalem area,
particularly in those providing greater care. Moreover, significant cognitive
impairment is probably under-reported in the medical records.
PMID- 17026776
TI - Fatigue states after cancer treatment occur both in association with, and
independent of, mood disorder: a longitudinal study.
AB - BACKGROUND: Persistent fatigue is recognised as one of the most common, ongoing
symptoms reported by patients following cancer treatment and may have profound
effects on the quality of life. However, recent cross-sectional studies also
highlight the close relationship between cancer related fatigue (CRF) and
diagnoses of depression or anxiety disorder. There is currently limited
information about the relationships between these conditions over time. We sought
to examine the longitudinal relationships between fatigue and mood disorder in
women treated with adjuvant therapy for early stage breast cancer. METHODS: Women
who had recently completed adjuvant therapy for Stage I or II breast cancer (n =
212) were sent a questionnaire with established case thresholds for clinically
significant fatigue and psychological disorder, as well as a questionnaire
assessing disability. Potentially relevant variables linked to fatigue states,
including age, treatment modality, menopausal status, and hematological indices
were recorded. The illness outcomes were assessed over 48 months of follow-up.
RESULTS: The 176 women who responded to the questionnaire (84%) had a mean age of
55 (range 24-83) years and had completed adjuvant treatment on average 10 (range
4.7-16.3) months previously. Radiotherapy had been administered, either alone
(50% of women) or in combination with chemotherapy (36%). Responses from 87 women
(48%) indicated a significant fatigue state (termed here post-cancer fatigue;
PCF), and from 59 women (33%) responses indicated significant psychological
distress. Thirty-four women (19%) were cases of fatigue alone (i.e. unaccompanied
by psychological disorder), whereas 52 (30%) were cases of both disorders.
Multivariate analysis did not reveal any association between demographic,
clinical or laboratory variables, and caseness for PCF. Self-reported functional
disability was significantly associated with fatigue. Follow-up at 24, 36 and 48
months revealed high rates of ongoing PCF in conjunction with psychological
distress, despite falling rates of psychological distress alone and fatigue
alone. CONCLUSION: Post-cancer fatigue was prevalent and sustained on follow-up.
Concurrent psychological disorder was evident in the majority, but not all, cases
of PCF and tended to be sustained over time. Further prospective cohort studies
to define the longitudinal co-morbid relationships between fatigue, mood
disorder, and ongoing disability after cancer treatment are indicated.
PMID- 17026779
TI - Visual hallucinations and amnesia associated with zolpidem triggered by
fluvoxamine: a possible interaction.
PMID- 17026780
TI - A practice audit of maintenance electroconvulsive therapy in the elderly.
PMID- 17026781
TI - Implications of daily, monthly and seasonal variation of new referrals for
working patterns of a community mental health team.
PMID- 17026782
TI - Catechol-o-methyltransferase gene polymorphism in dementia with Lewy bodies
related psychosis: evidence for a genetic predisposition.
PMID- 17026783
TI - Towards education-fair dementia screening.
PMID- 17026785
TI - The role of a drug holiday: even patients with cancer need a vacation.
PMID- 17026784
TI - Noradrenaline-induced smooth muscle relaxation in the specific region of canine
facial vein: implications for facial and cranial circulation.
AB - This study was performed to investigate the heterogeneity of physiological and
pharmacological properties in segments of the facial veins with special reference
to selective brain cooling. Canine facial veins were isolated and the isometric
tension of each segment was measured using the organ bath technique. Vessels in
the segments of the facial veins that run opposite to the buccal cavity
automatically produced myogenic tone and tended to show spontaneous contractions,
but vessels in other segments did not. When no contractile agent was used for
precontraction, noradrenaline and adrenaline produced dose-dependent relaxations
in the former venous segments, but contractions in the latter ones. A Schild plot
analysis for metoprolol against denopamine and for ICI118,551 against salbutamol
showed that the venous segments running opposite the buccal cavity contained both
beta(1)- and beta(2)-adrenoceptors, but the other venous segments contained only
beta(2)-adrenoceptors. Electrical field stimulation-induced tetrodotoxin
sensitive relaxations in the former venous segments were diminished by
pretreatment with metoprolol, but not with ICI118,551, indicating that the
electrical stimulation-induced relaxation may be related to the activation of
beta(1)-adrenoceptors in the venous smooth muscles. In conclusion, the
heterogeneity of the functional properties, especially in the distribution of
beta-adrenoceptors, in different segments of canine facial veins was observed in
the present study, and autoregulatory mechanisms, humoral mechanisms, and neural
mechanisms were suggested to affect cranial venous drainage.
PMID- 17026786
TI - Highlights from: 42nd Annual Meeting of the American Society of Clinical
Oncology.
PMID- 17026787
TI - Safety of bevacizumab with fluoropyrimidine-based regimens for first-line
treatment of metastatic colorectal cancer.
PMID- 17026788
TI - Do all patients with metastatic colorectal cancer need chemotherapy until disease
progression?
AB - The question of continuous versus intermittent chemotherapy for patients with
metastatic colorectal cancer has been an ongoing issue of debate for determining
the optimum duration of treatment. The results from 2 major trails addressing
this issue were recently presented at the 2006 Annual Meeting of the American
Society of Clinical Oncology. The OPTIMOX2 trial evaluated the efficacy and
safety of oxaliplatin reintroduction after a complete chemotherapy-free interval
or maintenance therapy in patients with previously untreated disease. The GISCAD
(Italian Group for the Study of Digestive Tract Cancer) study investigated the
utility of intermittent versus continuous irinotecan-based chemotherapy. Both
studies demonstrated that chemotherapy can be administered intermittently without
affecting the overall efficacy of treatment.
PMID- 17026789
TI - Liver resection for metastatic colorectal cancer in the age of neoadjuvant
chemotherapy and bevacizumab.
AB - Hepatic metastases from colorectal carcinoma (CRC) were once thought to portend a
uniformly grim outcome; however, improvements in chemotherapeutic and surgical
approaches have led to significant advances as well as new clinical challenges.
Some 60% of the 150,000 patients diagnosed with CRC each year in the United
States will develop hepatic metastases. Only a fraction of these metastases are
resectable at the time of presentation, but an increasing number of patients are
able to undergo resection after neoadjuvant chemotherapy. Additionally, recent
trials have demonstrated the efficacy of using chemotherapy with bevacizumab as
first-line therapy for metastatic CRC, but how this treatment will affect
surgical resection is unknown. Herein, we review the recent literature regarding
neoadjuvant chemotherapy for hepatic metastases from CRC, discuss key aspects of
the basic science of hepatic regeneration with regard to angiogenic mediators,
and outline the key problems to be solved so that a rational strategy can be
developed to treat patients with hepatic colorectal metastases in the age of
neoadjuvant chemotherapy and antiangiogenic drugs.
PMID- 17026791
TI - Epidermal growth factor receptor and epidermal growth factor receptor variant III
gene expression in metastatic colorectal cancer.
AB - PURPOSE: The epidermal growth factor receptor (EGFR) variant type III (variously
called EGFRvIII, de2-7 EGFR, or triangle upEGFR) has an in-frame deletion of the
extracellular domain and is found in numerous types of human tumors. Because
EGFRvIII has been reported to be tumor specific and has oncogenic potential, it
is being investigated as a potential therapeutic target, but to our knowledge,
there is only 1 previous report about EGFRvIII by immunohistochemistry in
colorectal cancer. Our aim was to indicate the frequency of gene expressions of
EGFRvIII and EGFR in metastatic colorectal cancer (mCRC). PATIENTS AND METHODS:
Forty-five patients with mCRC who received the chemotherapy for metastatic
disease were analyzed for the EGFRvIII variant. Paraffin-embedded tumor tissues
were dissected using laser-captured microdissection and analyzed for the EGFR and
EGFRvIII messenger RNA expression using a quantitative real-time reverse
transcriptase polymerase chain reaction method. Gene expression values (relative
messenger RNA levels) are expressed as ratios (differences from the cycle
threshold values) between the target gene and internal reference gene (beta
actin). Twenty-five women and 20 men with a median age of 55 years (range, 25-76
years) were included in this study. RESULTS: We did not find any expression of
EGFRvIII in these 45 patients except for control cell lines as U87.EGFRvIII.
However, EGFR gene expression was found in 43 of 45 (95.6%) with a range of 0.38
2.83. CONCLUSION: Our results demonstrate that the expression of EGFRvIII is
rare, but most colon cancer demonstrates EGFR gene expression. We conclude that
EGFRvIII does not play an important role in mCRC.
PMID- 17026790
TI - Phase I study of gefitinib plus FOLFIRI in previously untreated patients with
metastatic colorectal cancer.
AB - BACKGROUND: In this study, the maximum tolerated dose and toxicity profile of
FOLFIRI (infusional fluorouracil [5-FU]/leucovorin/irinotecan) plus gefitinib (an
oral inhibitor of the epidermal growth factor receptor) were evaluated as first
line therapy in patients with metastatic colorectal cancer. PATIENTS AND METHODS:
Sixteen patients participated in this study. Oral gefitinib was administered at
250 mg or 500 mg daily in 2 dose-escalation cohorts. FOLFIRI was administered
without dose escalation on a 14-day cycle with treatment on day 1 with irinotecan
180 mg/m2, leucovorin 200 mg/m2, and 5-FU 400 mg/m2 bolus, followed by 5-FU 2400
mg/m2 continuous infusion over 46 hours. RESULTS: The maximum tolerated dose of
gefitinib was 250 mg, with diarrhea and neutropenia noted as the principal dose
limiting toxicities. Dose reductions in 5-FU and irinotecan were required in 4
patients because of diarrhea and 1 patient because of neutropenia. A partial
response was observed in 25% of patients, and 56% had stable disease for > 12
weeks, corresponding to a disease control rate of 81%. CONCLUSION: These findings
suggest that gefitinib can be safely combined with FOLFIRI as first-line
treatment of metastatic CRC and support the safety of further investigations of
EGFR tyrosine kinase inhibitors with multiagent chemotherapy in this patient
population.
PMID- 17026792
TI - Hand-foot syndrome variant in a dihydropyrimidine dehydrogenase-deficient patient
treated with capecitabine.
AB - We present a case with dihydropyrimidine dehydrogenase (DPD) deficiency that
manifested a variant of hand-foot syndrome (HFS). A 52-year-old man received
capecitabine for adjuvant treatment of rectal cancer. On the ninth day of the
first cycle, he presented to the clinic with a rash on the dorsum of both hands
accompanied by symptoms of pain, erythema, swelling, and desquamation consistent
with grade 3 HFS. The palms of his hands and soles of his feet were only tender
with no apparent rash or discoloration. Dihydropyrimidine dehydrogenase activity
was evaluated by radio assay using peripheral blood mononuclear cells.
Dihydropyrimidine dehydrogenase activity was below normal: 0.12 nmol/minute/mg
protein. Capecitabine was not resumed, and the rash resolved in 3 weeks with the
use of pyridoxine and Udderly Smooth balm. Interestingly, HFS is rarely seen with
5-fluorouracil regimens containing selective DPD-inhibitors. This patient with
DPD deficiency manifested a variant of HFS. The pharmacologic basis for the
development of HFS in DPD-deficient patients warrants further investigation.
Dihydropyrimidine dehydrogenase deficiency, if undiagnosed, can lead to death. In
addition to severe to life-threatening toxicities akin to 5-fluorouracil,
capecitabine can lead to unusual variants of common toxicities, including HFS, in
DPD-deficient patients.
PMID- 17026793
TI - Ocular toxicity related to cetuximab monotherapy in patients with colorectal
cancer.
AB - Cetuximab is a monoclonal antibody that specifically blocks the epidermal growth
factor receptor pathway. Cetuximab is now a standard drug to treat refractory
advanced colorectal cancer. The most common side effect is a rash, seen in most
patients. Ocular toxicity is uncommon. We report 2 cases of ocular toxicity
characterized by blepharitis and conjunctivitis related to cetuximab
administration. Strategies for management are discussed.
PMID- 17026794
TI - Streptococcus suis endocarditis and colon carcinoma: a case report.
AB - Streptococcus bovis has classically been associated with colorectal carcinomas in
literature. Curiously enough, no other Streptococcus species have hitherto been
associated with such a malignancy or any other tumors. This report presents a
case of early-stage colorectal carcinoma diagnosed in a patient with infection
with the related Streptococcus species S suis. A discussion of possible
pathogenetic implications follows.
PMID- 17026796
TI - Assessing progress against prostate cancer.
PMID- 17026795
TI - Phase III multicenter randomized clinical trial to evaluate the safety and
efficacy of CoFactor/5-fluorouracil/bevacizumab versus leucovorin/5
fluorouracil/bevacizumab as initial treatment for metastatic colorectal
carcinoma.
PMID- 17026797
TI - Highlights from: the third International Congress on Kidney and Bladder Cancer.
Orlando, FL; August 3-6, 2006.
PMID- 17026798
TI - Current data with mammalian target of rapamycin inhibitors in advanced-stage
renal cell carcinoma.
AB - Mammalian target of rapamycin (mTOR) is the key regulator of cell growth and
proliferation. Alterations in the mTOR signaling pathway can lead to neoplastic
transformation and progression. The inhibition of mTOR blocks the progression of
the cell cycle from G1 to S phase, leading to cell growth arrest and apoptosis.
Thus, mTOR is a promising target for the treatment of human malignancies.
Rapamycin and its analogues, including temsirolimus, everolimus, and AP23573,
block the mTOR signaling pathway and induce a cellular state akin to starvation,
with significant antitumor activity in a variety of malignancies, including renal
cell carcinoma (RCC). Current data from ongoing clinical trials suggest that mTOR
targeted therapy with rapamycin derivatives is well tolerated with significant
clinical activity in patients with advanced-stage RCC. Specifically, temsirolimus
as monotherapy has demonstrated improved progression-free and overall survival in
patients with poor-risk advanced-stage RCC. Everolimus has also demonstrated
promising antitumor activity in patients with metastatic RCC. However, optimal
dose, treatment schedule, selection of patients, and appropriate combination
strategies with other novel agents need to be defined for mTOR-targeted therapies
in the treatment of advanced-stage RCC.
PMID- 17026799
TI - Interleukin-2 therapy of metastatic renal cell carcinoma: update of phase III
trials.
AB - High-dose bolus interleukin-2 (IL-2) was granted Food and Drug Administration
approval for the treatment of metastatic renal cell carcinoma based on its
ability to produce durable responses in a small number of patients. Results from
randomized phase III trials suggest that regimens involving lower doses of IL-2
alone or in combination with interferon produce fewer tumor regressions of
decreased overall quality. Because of the toxicity and limited efficacy of this
treatment, recent studies have focused on identifying predictors of response (or
resistance) to IL-2 therapy. This year, investigators will launch a clinical
trial designed to prospectively determine whether patients who are more likely to
respond to high-dose IL-2 can be identified before therapy is initiated.
PMID- 17026800
TI - Adjuvant therapy of renal cell carcinoma.
AB - Metastatic renal cell carcinoma (RCC) has a highly variable natural history and
carries a dismal prognosis. Unlike many other tumors, RCC is generally
unresponsive to cytotoxic, hormonal, and radiation adjuvant therapies after
cytoreductive surgery. Different modalities of treatment have been tried and
tested with modest success. Until recently, only immunotherapies such as
interleukin-2 and interferon-alpha have been shown to provide a response, albeit
in a minority of patients and often with severe treatment-associated toxicities.
Other adjuvant therapies, such as active specific immunotherapy with Bacillus
Calmette-Guerin and autologous renal tumor cell vaccines, have not provided
alternative solutions. Recent approaches include heat-shock protein peptide
complex 96 vaccine and cG250 monoclonal antibody therapy. Novel targeted
therapies have been developed using our knowledge of the molecular genetics that
belie RCC. This culminated in sorafenib and sunitinib, the first Food and Drug
Administration-approved drugs for RCC in more than a decade in the United States.
The future will see further trials being carried out in the development of
targeted therapies with emphasis placed on patient selection. Staging systems
will need to be updated to integrate molecular biomarkers, which could
potentially act not just as diagnostic and prognostic predictors, but also as
tools for appropriate patient selection for treatment. In the future, this could
potentially lead us to our ultimate goal of personalized medicine.
PMID- 17026801
TI - A phase II study of weekly paclitaxel/estramustine/carboplatin in hormone
refractory prostate cancer.
AB - PURPOSE: The objective of this phase II study was to determine the response rate
in patients with hormone-refractory prostate cancer given
paclitaxel/estramustine/carboplatin for weeks 1, 2, and 3 of a 4-week cycle.
PATIENTS AND METHODS: Eighty-four patients were registered into the trial.
Paclitaxel 80 mg/m2 and carboplatin area under the curve of 2 were administered
intravenously on days 2, 9, and 16, and oral estramustine 280 mg 3 times daily
was given on days 1-3, 8-10, and 15-17 for 6 cycles. Eastern Cooperative Oncology
Group performance status 0, 1, and 2 was 46%, 41%, and 13%, respectively, and
median age was 70 years (range, 53-82 years), with 58 patients (69%) aged > 65
years. The majority of patients (83%) were white. Fifteen patients (18%) had
received previous chemotherapy, 61 patients (73%) had undergone previous surgery,
and 51 patients (61%) had received previous external-beam radiation therapy.
RESULTS: Intent-to-treat analysis revealed a > or = 50% prostate-specific antigen
decrease rate of 61%. Median survival was 15.3 months. The most frequent grade >
or = 3 toxicities included fatigue (11%), nausea (10%), neutropenia (9%), anemia
(6%), and vomiting (6%). CONCLUSION: Paclitaxel/estramustine/carboplatin
administered in a weekly regimen is highly effective in the treatment of hormone
refractory prostate cancer and can be administered with reasonable safety in an
outpatient setting.
PMID- 17026802
TI - Intermittent hormone therapy in nonmetastatic prostate cancer.
AB - PURPOSE: The object of this study was to evaluate the duration of response to
intermittent androgen deprivation (IAD) in patients with nonmetastatic recurrent
or localized prostate cancer. PATIENTS AND METHODS: One hundred ten patients
received IAD from February 1992 to February 2005. One hundred three patients were
treated after failure of primary radiation therapy and/or prostatectomy, with the
remaining 7 patients treated primarily with IAD. The median duration of treatment
cycle was 6 months. Patients were considered resistant to hormone therapy if the
prostate-specific antigen (PSA) level increased, with castrate levels of
testosterone. At the time of initial diagnosis, the median Gleason score was 7
(range, 4-9), and tumor stages were as follows: T1/T2 (n = 73), T3 and T4 N1 (n =
34), and other (n = 3). The median PSA at the initiation of IAD was 8.25 ng/mL.
RESULTS: The median follow-up after beginning IAD was 45.5 months. Patients
received a median of 2 cycles (range, 1-9 cycles). Ninety-four of 110 patients
(85.5%) remained responsive to IAD. Sixteen patients (14.5%) progressed to become
refractory to primary hormone treatment. Patients with a higher tumor stage (T3
and T4) were significantly more likely to develop resistance. The median time to
become refractory to hormone therapy was 47.9 months (range, 9.4-93.4 months).
Five patients were put on secondary continuous hormone treatment, and 3 of them
developed resistance at a median of 9 months. One patient was put on a secondary
IAD and was still responding at the last follow-up. CONCLUSION: With 85.5% of the
original patient population still responding to the primary hormone therapy at
45.5 months of follow-up, IAD appears to be a viable option for patients with
biochemical failure after local radiation therapy. A pattern of shortening time
between cycles and an increasing nadir PSA level with each successive cycle is
consistent with the gradual development of hormone resistance.
PMID- 17026803
TI - Thalidomide/estramustine/paclitaxel in metastatic androgen-independent prostate
cancer.
AB - BACKGROUND: This is a phase I/II trial of thalidomide with estramustine and
paclitaxel in men with androgen-independent prostate cancer (AIPC) who underwent
previous chemotherapy. PATIENTS AND METHODS: Men with progressive AIPC were
treated with oral thalidomide (200 mg, 400 mg, or 600 mg daily), intravenous
paclitaxel (100 mg/m2 over 3 hours on days 3 and 10), and oral estramustine (140
mg 3 times daily on days 1-5 and days 8-12) every 21 days. RESULTS: Phase I:
first cycle dose-limiting toxicity occurred in 0 of 3 patients at 200 mg
thalidomide daily, 0 of 3 at 400 mg daily, and 1 of 3 at 600 mg daily (the
designated maximum tolerated dose). Phase II: twenty-nine of 38 evaluable
patients (76%; 95% confidence interval, 67%-87%) experienced a 50% decrease in
prostate-specific antigen level. Five of 18 patients (28%) with measurable
disease exhibited an objective response. Nine of 14 patients (64%) with disease
refractory to previous taxane therapy had 50% decreases in prostate-specific
antigen level. Grade 3/4 adverse events included neutropenia (9 of 39 [23%]),
fatigue (9 of 39 [23%]), dyspnea (8 of 39 [21%]), and thromboembolic events (7 of
39 [18%]). Cumulative dose-limiting toxicity rates were minimal (13%) with
thalidomide at 200 mg daily. CONCLUSION: The profile of activity of
thalidomide/paclitaxel/estramustine in taxane-refractory AIPC warrants further
investigation.
PMID- 17026804
TI - Phase II trial of adjuvant gemcitabine plus cisplatin-based chemotherapy in
patients with locally advanced bladder cancer.
AB - BACKGROUND: Despite the general acceptance of gemcitabine/cisplatin in metastatic
bladder cancer, its role and tolerability in the adjuvant setting, in which renal
insufficiency is common, is unclear. PATIENTS AND METHODS: A total of 39 patients
with locally advanced transitional cell carcinoma of the bladder (T2-T4, N0-N2)
were treated with 4 cycles of gemcitabine/cisplatin/amifostine after radical
cystectomy. All toxicities were evaluated by the National Cancer Institute Common
Toxicity Criteria. Tumor samples were immunohistochemically stained for pRB, p53,
and p16. RESULTS: Thirty-five patients (90%) completed 4 cycles of chemotherapy.
Eleven patients (28%) experienced grade 4 hematologic toxicity, and 14 patients
(36%) experienced grade 3 nonhematologic toxicity. The median increase in
creatinine was 0.3 mg/dL. With a median follow-up of 22.8 months (range, 7-70
months), 13 patients (33%) had recurrent disease, 1 patient at 6 years after
completion of therapy. Twelve patients (31%) died, including 11 (28%) with
recurrent disease. Thirty-three tumor blocks were evaluated for pRB, p53, and p16
alterations. In an exploratory analysis, altered expression of p53, p16, and pRB
was found in 15 (45%), 22 (67%), and 30 patients (91%), respectively. No
association between altered p53 and disease-free or overall survival was
detected, but altered p16 and pRB expression was associated with better outcome
(P < or = 0.001). CONCLUSION: Gemcitabine/cisplatin with amifostine is tolerated
in the adjuvant setting for patients with locally advanced bladder cancer. The
favorable prognostic value of altered p16 and pRB raises the hypothesis of a
relative beneficial effect of chemotherapy in this population but needs
verification in other studies.
PMID- 17026805
TI - Phase II trial of docetaxel/capecitabine in hormone-refractory prostate cancer.
AB - BACKGROUND: Docetaxel is the most active single agent in the treatment of hormone
refractory prostate cancer (HRPC). Because of the preclinical and clinical
evidence of synergy of capecitabine and docetaxel, it was hypothesized that this
combination would be active and tolerable in HRPC. PATIENTS AND METHODS: Patients
received docetaxel 60 mg/m2 intravenously over 60 minutes on day 1 of each 21-day
cycle and capecitabine 1000 mg/m2 administered orally twice daily on days 1-14 of
each cycle for a maximum of 8 cycles or until disease progression or intolerable
toxicity. Seventy-seven patients were enrolled at 43 US Oncology sites. The
median age was 69.3 years (range, 48-86 years); 86% were white, and the Eastern
Cooperative Oncology Group performance status scores of 0 and 1 were 49% and 51%
respectively. Sixty-nine (90%) patients were evaluated for prostate-specific
antigen response. RESULTS: Overall, 41% of patients had a decreased prostate
specific antigen level > or = 50%. There were 4 complete responses (6%), 24
partial responses (35%), 29 incidences of stable disease (43%), and 11 incidences
of progressive disease (16%). Nine patients has stable disease > or = 6 months
and the clinical benefit rate was 54%. The median time to response was 1.5 months
(range, 1-16.9 months). The estimated survival at 12 and 24 months (range, < 1-27
months). There were no treatment-related deaths. Grade 3/4 toxicities included
neutropenia (50%), leukopenia (22%), hand-foot syndrome (17%), fatigue (11%), and
nausea (11%). CONCLUSION: Docetaxel/capcitabine is an active and tolerable
combination in HRPC. Toxicity was acceptable and anticipated. Response rate and
survival are comparable with other docetaxel combinations.
PMID- 17026806
TI - Stromal-epithelial interaction in prostate cancer progression.
AB - Cancer is not a single-cell disease, and its existence and behavior are
constantly modulated by the host. Cancer gene expression and genetics are also
highly dynamic and are regulated epigenetically by the host through gene
environment interaction. In this article, we describe the molecular pathways
leading to an unusual property of cancer cells: the ability to mimic the host
microenvironment and, in particular, the characteristics of osteomimicry and
vasculogenic mimicry, which are likely to be regulated by soluble and insoluble
factors in the tumor-adjacent microenvironment. We also discuss the importance of
host inflammatory and stem cells that contribute to the growth and survival of
cancer cells. By understanding the salient features of cancer-host interaction,
novel therapeutics might be developed to target the cancer and its host in the
treatment of lethal prostate cancer metastases.
PMID- 17026807
TI - Therapy for stage III non-small-cell lung cancer: Bob Beamon or Chemo-Beamo?
PMID- 17026809
TI - Aurora kinase inhibitors: a new class of targeted drugs in cancer.
AB - Aurora kinases (A, B, and C) are essential for spindle assembly, centrosome
maturation, chromosomal segregation, and cytokinesis. Aurora kinases A and B are
overexpressed in many cancers, including non-small-cell lung cancer and
mesothelioma. Small-molecule inhibitors selective for aurora kinases have shown
promising activity in preclinical tumor models. To date, phase I studies with
aurora kinase inhibitors have shown that myelosuppression is the dose-limiting
toxicity, and disease stabilization was achieved in a number of tumor types,
including non-small-cell lung cancer. Phase II trials are under way in selected
tumor types. This article reviews the biology of aurora kinases, their potential
role in the treatment of lung cancer, and challenges in the clinical development
of this unique class of antineoplastic agents.
PMID- 17026810
TI - Future trends in patient-reported outcomes assessment for patients with advanced
stage lung cancer receiving targeted therapy.
AB - Recent advances in cancer cell biology have led to the development of therapeutic
agents that target pathways critical to the development and progression of
disease. These so-called "targeted therapies" might offer patients a more
tolerable alternative to traditional systemic chemotherapy that often achieves
therapeutic benefit at the cost of debilitating side effects. Several targeted
agents have been recently tested in clinical trials of advanced-stage lung
cancer. As interest in these therapies grows, an understanding of their impact on
the patient's well-being will be important. Patient-reported outcome measures
such as formal assessments of health-related quality of life and disease symptoms
provide a useful means for addressing the impact of therapy from the perspective
of the patient. We summarize the most commonly used measures of health-related
quality of life in clinical trials of advanced-stage lung cancer. Although
existing measurement systems do provide adequate coverage of many important
patient-related outcome issues, the advent of targeted therapies in advanced
stage lung cancer does expose several measurement gaps. We highlight some of
these gaps by reviewing a representative sample of recently conducted clinical
trials of targeted lung cancer therapy and offer insight as to how these gaps can
be filled. We also briefly discuss a set of issues unique to patients receiving
targeted therapy (eg, perceptions of treatment efficacy, treatment compliance,
patient satisfaction, and treatment convenience) and consider a few methodologic
concerns unique to patients with advanced cancer.
PMID- 17026811
TI - Evolving role of interventional pulmonology in the interdisciplinary approach to
the staging and management of lung cancer: bronchoscopic mediastinal staging of
lung cancer.
AB - Mediastinal lymph node involvement is present in 26%-38% of patients with non
small-cell lung cancer at the time of diagnosis, and it is often the most
significant factor in determining surgical resectability. Complete and accurate
mediastinal staging of lung cancer is essential for determining prognosis and for
guiding optimal treatment strategies. Computed tomography and positron emission
tomography are the most widely used noninvasive means for mediastinal staging in
lung cancer. However, based on their reported specificities, computed tomography
and positron emission tomography findings should be verified by cytohistologic
sampling. In recent decades, the technique of transbronchial needle aspiration
(TBNA) has been developed, permitting the bronchoscopist to obtain cytohistologic
material from the hilar and mediastinal lymph nodes adjacent to the
tracheobronchial wall. The technique of TBNA has a great specificity, is safe and
cost-effective compared with surgical methods, and can be performed during the
initial diagnostic bronchoscopy. Transbronchial needle aspiration sensitivity is
76%-78% but is highly influenced by several factors. Endobronchial ultrasound has
been proposed as a means for improving TBNA sensitivity. Recently, a new type of
bronchoscope with a built-in convex ultrasound probe directly attached to the tip
has been developed to guide TBNA under real-time imaging. Reports on this
innovative technique reveal a sensitivity of 94%-95.7%, which is superior to the
reported sensitivity of surgical methods. However, ultrasound-guided TBNA and
traditional TBNA should be considered complementary techniques, because their
integration is likely to become the optimal staging strategy for patients with
lung cancer.
PMID- 17026812
TI - Long-term survival with concurrent chemoradiation therapy followed by
consolidation docetaxel in stage IIIB non-small-cell lung cancer: a phase II
Southwest Oncology Group Study (S9504).
AB - PURPOSE: Here we report 5-year survival data from S9504, a Southwest Oncology
Group phase II trial evaluating consolidation docetaxel after concurrent
cisplatin/etoposide and thoracic radiation therapy in patients with
pathologically documented stage IIIB non-small-cell lung cancer. Survival
outcomes were compared with a predecessor study (S9019) with identical
eligibility, staging criteria, and treatment, excepting docetaxel consolidation.
PATIENTS AND METHODS: Treatment consisted of cisplatin 50 mg/m(2) per day on days
1, 8, 29, and 36; etoposide 50 mg/m(2) per day on days 1-5 and 29-33; and
concurrent thoracic radiation therapy (total dose, 61 Gy). Consolidation
docetaxel (75 mg/m(2) initial dose) started 4-6 weeks after completion of
chemotherapy. RESULTS: Concurrent chemotherapy was generally well tolerated, with
a low level of radiation-related esophagitis; 2 patients died from pneumonitis.
Grade 3/4 neutropenia during consolidation docetaxel was common. At a median
follow-up of 71 months, median progression-free survival was 16 months; median
survival 26 months; and 3-, 4-, and 5-year survival rates were 40%, 29%, and 29%,
respectively. Brain metastasis was the most common site of failure. In the
predecessor trial S9019, median survival was 15 months, and 3-, 4-, and 5-year
survival rates were 17%, 17%, and 17%, respectively. CONCLUSION: The 5-year
survival rate in S9540 of 29% compares favorably with the predecessor trial S9019
and other treatment approaches currently used in this patient population. A phase
III trial designed to validate the concept of consolidation docetaxel is
presently under way.
PMID- 17026813
TI - Phase II trial of sequential chemotherapy followed by chemoradiation, surgery,
and postoperative chemotherapy for the treatment of stage IIIA/IIIB non-small
cell lung cancer.
AB - BACKGROUND: The optimal treatment of locally advanced non-small-cell lung cancer
remains a challenge. Although the benefit of combined chemoradiation has been
established, the optimal chemotherapy regimen, timing of full-dose chemotherapy,
and how best to combine chemotherapy with radiation to maximize systemic and
radiosensitizing effects remain unclear. PATIENTS AND METHODS: Twenty-nine
patients with pathologically confirmed stage IIIA/IIIB non-small-cell lung cancer
were included in a phase II trial of sequential carboplatin/paclitaxel followed
by chemoradiation, surgery, and postoperative gemcitabine. Twenty-five patients
(86%) completed the concurrent chemotherapy and radiation therapy phase and were
eligible for surgery. At restaging, 7 patients (21%) showed disease progression.
Seventeen patients (59%) went on to surgery. Few were able to tolerate full
postoperative chemotherapy. RESULTS: The 1-year overall survival rate was 61%,
with a 2-year survival rate of 56%. Median overall survival was 25.2 months.
Seven of the patients are alive and without recurrence at the time of this
writing. Our median follow-up time was 22.2 months. Reversible grade 3/4
toxicities were fairly common, experienced in 45% of patients. CONCLUSION: Our
results with this combined modality approach are comparable with those of
previous, similar studies. Postoperative chemotherapy after initial combined
modality therapy is often not feasible, reinforcing the value of initial systemic
therapy. Long-term results are still suboptimal and await studies adding targeted
therapies to our usual chemotherapy/radiation approaches.
PMID- 17026814
TI - Topotecan therapy in patients with relapsed small-cell lung cancer and poor
performance status.
AB - PURPOSE: Topotecan is generally well tolerated and active in patients with
relapsed small-cell lung cancer (SCLC) and poor performance status (PS). In this
study, we investigated whether treatment with topotecan is associated with
improvement in PS as measured by the rate of conversion from PS 2 to PS 0/1.
PATIENTS AND METHODS: A retrospective analysis of data from 7 clinical trials (N
= 795) investigating topotecan in patients with relapsed SCLC was performed. All
patients received topotecan 1.25-1.5 mg/m2 daily on days 1-5 of a 21-day cycle.
Demographics were similar for patients with PS 2 and PS 0/1. A total of 152
patients with PS 2 at baseline received 502 cycles (median, 2 cycles; range, 1-14
cycles) of therapy, and 32 (21%) experienced PS improvement to PS 0/1 that lasted
for > or = 2 cycles. RESULTS: Overall, 50% of patients who experienced PS
conversion also exhibited an objective antitumor response, compared with 8% of
patients with PS 2 who had no improvement in PS and achieved a response.
Similarly, median overall survival was longer for patients with PS improvement
(37 weeks; 95% confidence interval, 29.6-49.4 weeks) compared with patients with
PS 2 who had a response but no PS improvement (10.4 weeks; 95% confidence
interval, 8.7-13.6 weeks). A substantial proportion of patients with PS 2 and
relapsed SCLC experienced PS improvement during topotecan treatment. These
patients had a substantially longer median survival and a higher response rate
compared with the overall trial population. CONCLUSION: Improvement in PS appears
to be a good indicator of benefit from topotecan therapy.
PMID- 17026815
TI - Randomized, multicenter, open-label phase II study of gemcitabine plus single
dose versus split-dose carboplatin in the treatment of patients with advanced
stage non-small-cell lung cancer.
AB - BACKGROUND: Gemcitabine/carboplatin is a convenient and effective treatment for
advanced-stage non-small-cell lung cancer (NSCLC), but modification of the
schedule to diminish thrombocytopenia is worthwhile. PATIENTS AND METHODS: One
hundred fifty-eight chemotherapy-naive patients with stage IIIB/IV NSCLC were
randomized from 15 centers in Germany to receive gemcitabine 1250 mg/m(2) on days
1 and 8 plus carboplatin area under the curve 5 on day 1 (arm A) or carboplatin
area under the curve 2.5 on days 1 and 8 (arm B), every 21 days for 4 cycles.
RESULTS: The 2 arms (A vs. B) were well balanced with regard to patient baseline
characteristics: stage IV 72.5% versus 69%, median Eastern Cooperative Oncology
Group performance status 1 versus 1. The incidence of grade 3/4 hematologic
toxicity was as follows (percentage of patients in arm A vs. B): leukopenia 37.5%
versus 27% (P = 0.075), granulocytopenia 36% versus 36%, and thrombocytopenia 51%
versus 35% (P = 0.017). Nonhematologic toxicity was modest and comparable with
both schedules. The overall response rate was 46% versus 36% (P = 0.12), and 24%
versus 42% had stable disease. Median progression-free survival (5.8 months vs.
6.1 months) and overall survival (11.7 months vs. 10.7 months) were not
significantly different between arms A and B. CONCLUSION: Splitting the dose of
carboplatin between days 1 and 8 on the same days as gemcitabine results in a
significantly decreased incidence of severe thrombocytopenia, without
compromising the activity of the combination.
PMID- 17026816
TI - Cell-free DNA concentration in pleural fluid and serum: quantitative approach and
potential prognostic factor in patients with cancer and pleural effusions.
AB - PURPOSE: The presence of pleural effusions in patients with tumors is often
indicative of locally advanced or metastatic disease, and detection of malignancy
in effusion samples frequently leads to a disease upstaging. Our purpose was to
quantify the DNA in pleural effusion and serum in patients presenting pleural
effusion in order to assess the potential prognostic impact. PATIENTS AND
METHODS: The DNA level was determined by amplifying hRNase P in paired samples of
serum and pleural fluid in 70 consecutive patients with cancer showing pleural
effusion. A group of 30 patients without cancer was included. The correlation
between serum and pleural DNA was calculated. Survival curves according to serum
and pleural DNA were analyzed. RESULTS: Median DNA concentrations were greater in
patients with neoplasia than in patients without malignancy: 105 ng/mL versus 40
ng/mL (P = 0.001) in serum samples, respectively; 93 ng/mL versus 21 ng/mL (P =
0.001) in pleural fluids, respectively. A positive correlation between serum and
pleural levels was confirmed (r = 0.3; P < 0.05). Median survival time for
patients with serum DNA < or = 105 ng/mL was 11.03 months in contrast to only
3.63 months for patients with higher values (P = 0.036). Accordingly, median
survival time for patients with pleural DNA < or = 93 ng/mL was 12.3 months
versus only 4.63 months in case of higher levels (P = 0.027). CONCLUSION: This
study shows that there is a strong correlation between higher levels of free DNA
in pleural fluid or serum and malignancy. Survival is worse for patients with
higher DNA levels in serum and pleural fluid.
PMID- 17026817
TI - A multidisciplinary approach to management in a patient with bilateral superior
sulcus non-small-cell lung carcinoma.
AB - Superior sulcus tumors comprise a rare subset of non-small-cell lung carcinomas
that are particularly challenging to treat because of their location and extent
of nerve and vessel involvement. In this report, we present a case illustrating
the uncommon situation of a patient presenting with bilateral superior sulcus
tumors, and we review the latest combined therapeutic approach developed to
aggressively treat the more common unilateral presentation of these tumors.
PMID- 17026818
TI - Bortezomib dosing in relapsed multiple myeloma.
PMID- 17026820
TI - Targeting B-lymphocyte stimulator/B-cell activating factor and a proliferation
inducing ligand in hematologic malignancies.
AB - B-lymphocyte stimulator/B-cell activating factor (BLyS/BAFF) and a proliferation
inducing ligand (APRIL), members of the tumor necrosis family of ligands, are
expressed by monocytes, macrophages, and dendritic cells, and increased
expression of these ligands is noted in lymphomas and plasma cell malignancies.
BLyS and APRIL are essential for the survival of normal and malignant B
lymphocytes, and altered expression of BLyS or APRIL or the receptors B-cell
maturation, transmembrane activator and calcium-modulating cyclophilin ligand
interactor, or BAFF-R have been reported in various B-cell malignancies,
including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's
lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia. Levels of BLyS
(in the tumor and in the serum) increased with the transformation of the tumors
to a more aggressive phenotype. A high BLyS level inversely correlated with a
poor median overall survival, presence of constitutional symptoms, and increased
levels of lactate dehydrogenase in patients with non-Hodgkin's lymphoma.
Additionally, patients who responded to therapy had a lower BLyS level than those
with progressive disease. Several agents targeting BLyS and APRIL are currently
being pursued in phase I clinical studies in patients with B-cell malignancies.
PMID- 17026821
TI - Response to bortezomib and activation of osteoblasts in multiple myeloma.
AB - Histomorphometry and biochemical markers of bone turnover have shown that,
although osteoclast activity is increased in multiple myeloma (MM), mostly
through the receptor activator of nuclear factor-kappaB ligand/osteoprotegerin
axis, the key element in vivo to determine the presence or absence of osteolytic
lesions resides on the presence and activity of osteoblasts. The loss of bone
observed in MM is the result of an uncoupling of bone formation and bone
resorption. Bortezomib is a first-in-class proteasome inhibitor developed as an
antineoplastic agent with marked activity in relapsed/refractory MM. Response to
bortezomib has been related to a significant increase in alkaline phosphatase
(ALP). Increased ALP in patients responding to bortezomib was associated with a
parallel increase in bone-specific ALP and parathyroid hormone, suggesting that
response to bortezomib in MM is closely associated with osteoblastic activation.
Variation in markers of osteoblastic activation (such as ALP) have also predicted
response and response duration in patients with myeloma treated with bortezomib
(P < 0.0001). This clinical observation has been confirmed in an experimental
mouse model for primary human myeloma. The consequences of increased bone
anabolism on myeloma growth need to be closely evaluated in prospective trials.
PMID- 17026822
TI - Salvage chemotherapy in follicular non-Hodgkin's lymphoma: focus on tolerability.
AB - Follicular lymphoma (FL) is typically characterized by repeated remissions and
relapses, and many patients receive a number of therapeutic interventions during
their disease course. Although treatment options are evolving rapidly, stem cell
transplantation offers a potentially favorable impact on survival. In general,
many patients with FL are not eligible for this approach by virtue of age and/or
comorbid disease. Salvage chemotherapy consequently remains the mainstay of
treatment, being individualized according to disease and patient characteristics,
goals of therapy, and patient preference. Many of the cytotoxic agents used in
relapsed FL are highly myelotoxic, leading to significant morbidity and
mortality, including febrile neutropenia, hemorrhage, and impaired quality of
life. Nausea and vomiting can also be problematic, particularly with regimens
incorporating carmustine, cisplatin, and high-dose cyclophosphamide. Other acute
toxicities include mucositis, alopecia, extravasation injuries, and
neurotoxicity. Late toxicities can also occur, sometimes months or even years
after the administration of antineoplastic agents. Acute myeloid leukemias,
myelodysplastic syndromes, or solid tumors can occur after chemotherapy with
alkylating agents. The cardiotoxic profile of anthracycline antibiotics is well
recognized, and several agents, including carmustine and cyclophosphamide, can
cause lung injury. Persistent neurotoxicity, nephrotoxicity, ototoxicity, and
vascular toxicity have also been reported in association with chemotherapeutic
agents used in patients with relapsed FL. Novel therapeutic strategies might
allow patients to achieve longer remissions, potentially reducing lifetime
exposure to repeated cycles of chemotherapy and their attendant toxicities. These
could include the use of more efficient preparative and purging approaches in the
transplantation setting or the administration of rituximab maintenance therapy
after (immuno) chemotherapy induction or transplantation.
PMID- 17026823
TI - Updated guidelines on the management of cytomegalovirus reactivation in patients
with chronic lymphocytic leukemia treated with alemtuzumab.
AB - The anti-CD52 monoclonal antibody alemtuzumab is highly active in the treatment
of chronic lymphocytic leukemia (CLL) in patients with previously treated,
relapsed, and/or refractory CLL as well as in patients with previously untreated
disease. The general immunosuppressive impact and toxicities associated with
alemtuzumab therapy are largely predictable and manageable. In particular,
cytomegalovirus (CMV) reactivation is now a well-documented complication in
patients receiving alemtuzumab. This article discusses several strategies for
monitoring and treating CMV reactivation in patients with CLL receiving
alemtuzumab-based therapy and provides practical recommendations for CMV
management by building upon the guidelines published previously in 2004.
PMID- 17026824
TI - Weekly bortezomib/methylprednisolone is effective and well tolerated in relapsed
multiple myeloma.
AB - BACKGROUND: The standard schedule of bortezomib requires frequent infusions and
is often associated with dose-dependent, adverse effects such as sensory
neuropathy and thrombocytopenia. Because of the known additive effect between
bortezomib and glucocorticoid, we explored weekly bortezomib/methylprednisolone
in patients with relapsed multiple myeloma. PATIENTS AND METHODS: Twenty-nine
patients were treated at Indiana University with bortezomib (1.3 mg/m2) and
methylprednisolone (500-2000 mg) intravenously on days 1, 8, and 15 of 28-day
cycles. Response was evaluated using the Blade criteria. Twenty-one patients
(70%) had previous stem cell transplantation, and 13 were in third relapse or
higher. RESULTS: A response was observed in 18 patients (62%): 1 (3%) complete
response, 1 (3%) near complete response, and 16 (55%) partial responses. Six
(21%) had stable disease, and 5 (17%) had disease progression. The median time to
progression, which was defined from the beginning of therapy until progression,
was 6.6 months (95% confidence interval, 6.4-9.2 months). The median number of
treatment cycles was 6 (range, 2-12 cycles). The median overall survival was 20.2
months (lower 95% confidence interval, 13.1 months). The most common toxicities
were fatigue and gastrointestinal disturbances. Grade >or= 3 adverse effects
included neuropathy (2 grade 3), gastrointestinal side effects (1 grade 3), and
congestive heart failure (1 grade 3). CONCLUSION: The weekly
bortezomib/methylprednisolone regimen was well tolerated and yielded a response
rate comparable with the standard schedule of bortezomib alone. Our data support
further investigation of this regimen in larger patient cohorts.
PMID- 17026825
TI - Immunotherapy with rituximab/interleukin-2 after autologous stem cell
transplantation as treatment for CD20+ non-Hodgkin's lymphoma.
AB - BACKGROUND: Relapse of non-Hodgkin's lymphoma (NHL) remains a problem after
autologous stem cell transplantation (ASCT). Soon after ASCT, the immune system
is not very active, and this immune incompetence could thus result in decreased
ability for immune-mediated tumor eradication. The early addition of
immunotherapy after ASCT might decrease the incidence of relapse and prolong
survival. In an initial phase I/II trial at our center, the immune modulator
interleukin-2 (IL-2) increased over baseline natural killer and lymphokine
activated killer activity in vitro. Because rituximab can lyse CD20-bearing cells
by antibody-dependent cellular cytotoxicity, adding IL-2 to rituximab might boost
its effectiveness. It thus seemed reasonable to study this combination after
ASCT. The results of our phase II study are reported herein. PATIENTS AND
METHODS: Twenty patients with CD20+ NHL who had ASCT were treated. The median
time to starting therapy was 79 days (range, 49-100 days) after transplantation.
RESULTS: The majority of patients reported grade 200 ml and/or > or =12> or = after 200
microg of inhaled salbutamol) or non-reversible COPD. GSH, GSSG were measured in
induced sputum and blood. Protein carbonyls were evaluated by WB in sputum and IL
4 and IL-6 and TNF-alpha in plasma and sputum. GSH oxidation and protein
oxidation were lower in reversible COPD patients than in those with no
reversibility. The sputum eosinophil count was significantly higher in the
reversible group than in the non-reversible group, and IL-4 concentration was
higher in the same patients both in sputum and in plasma. In contrast, IL-6 and
TNF-alpha were increased in non-reversible COPD patients in both biological
samples. We conclude that airflow reversibility in COPD patients is associated
with airway oxidative stress and activation of eosinophil inflammatory pattern in
sputum and blood, suggesting that these patients could respond to specific
pharmacological treatment.
PMID- 17026848
TI - Relationship between specific serum IgE to Ascaris lumbricoides and onset of
respiratory symptoms in Bangladesh immigrants.
AB - The role of helminths in asthma and/or rhinitis and in allergic sensitization is
still unclear. We assessed the relationship between Ascaris-specific IgE,
respiratory symptoms and allergic sensitization in Bangladesh immigrants. 246
individuals were examined from 1996 to 2001. Serum total IgE, Ascaris IgE,
specific IgE to inhalant allergens, skin prick tests (SPT) and parasitological
evaluation of the stool were performed. Total serum IgE were significantly higher
in Ascaris-IgE positive (> 0.35 kU/L) individuals (806.5 [409.0-1436.0] kU/L vs.
207.0 [127.0-332.5] kU/L; P < 0.0001) and in subjects with respiratory symptoms
(413.0 [239.0-1096.0] kU/L vs. 259.5 [147.0-387.0] kU/L), (P < 0.0001), but not
in SPT positive subjects (413.0 [179.0-894.0] kU/L vs. 404.6 [305.0-1201.0] kU/L
(P = 0.5). Ascaris-specific IgE were detected in 48 subjects with respiratory
symptoms (40.0%) and in 46 subjects without respiratory symptoms (36.5%) (P =
0.5). The SPT positivity was similar between Ascaris-IgE seropositive (38.2%) and
Ascaris-IgE seronegative (38.1%) subjects (P = 0.9). Total IgE and length of stay
in Italy correlated with SPT positivity (OR 5.6 [CI 95% 1.5-19.8], P = 0.007, and
OR 1.5 [CI 95% 1.3-1.7], P< 0.0001), and with respiratory symptoms (OR 13.7 [CI
95% 3.0-62.4];, P = 0.0007, and OR 2.4 [CI 95% 1.9-3.0], P < 0.0001). Ascaris-IgE
were negatively associated with SPT positivity (OR 0.3 [CI 95% 0.1-0.8], P =
0.02) and with respiratory symptoms (OR 0.1 [CI 95% 0.04-0.7], P = 0.01). Our
findings favour the role of environmental factors in the development of
respiratory symptoms in immigrants, irrespective of Ascaris-IgE.
PMID- 17026849
TI - Immunoinflammatory activation during the acute phase of lacunar and non-lacunar
ischemic stroke: association with time of onset and diabetic state.
AB - Several studies have stressed the involvement of inflammation in the
pathophysiology of acute brain ischemia, but the role of immunoinflammatory
activation in diabetic stroke patients has not yet been fully evaluated. The aim
of our study was to evaluate immunoinflammatory activation of acute phase of
stroke in relation to time of symptoms onset, diabetic state and diagnostic
subtype. We enrolled 60 patients (32 diabetics; 28 non- diabetics) with acute
ischemic stroke and 123 subjects without acute ischemic stroke, and measured
levels of IL-1beta, TNF-alpha IL-6, IL-10, E-selectin, P-selectin, sICAM-1, sVCAM
1, VWF, 24-72 h and 7-10 days after stroke onset; TPA, PAI-1 plasma levels at 24
72h. Our stroke patients exhibited significantly higher plasma levels of
cytokines, selectins, adhesion molecules and PAI-1, and diabetic stroke patients
exhibited higher plasma levels of PAI-1 in comparison with non-diabetic ones.
Lacunar strokes in comparison with those non-lacunar exhibited significantly
lower levels of TNF-alpha and IL1-beta P-selectin and ICAM-1. Moreover, diabetic
patients with lacunar strokes exhibited a minor grade of immunoinflammatory
activation of the acute phase at 24-72h and 7-10 days after stroke onset. The
minor grade of immunoinflammatory activation of patients with lacunar strokes,
particularly diabetic ones, could be related to the minor extension of the
infarct size, owing to the typical microvascular disease of diabetic subjects
which could also explain the reported better outcome of this subtype of ischemic
stroke.
PMID- 17026850
TI - Dual effect of methylprednsolone pulses on apoptosis of peripheral leukocytes in
patients with renal diseases.
AB - It is well known that change in apoptosis may modulate the natural story of
illness, and that many drugs may act through modulation of apoptosis, but the
role of steroids in acting through apoptosis in different settings, including
renal diseases, has still to be elucidated. We studied the in vivo effects of
steroids by oral assumption (10 to 25 mg/deltacortene) or by intravenous pulses
(300 to 1000 mg/dose) on apoptosis and cellular subsets of peripheral
lymphocytes, by evaluating DNA-fragmentation and lymphocyte subsets in 79
subjects: 22 controls and 57 patients with various renal diseases (25 Lupus-GN,
19 membranous-GN (MGN), 6 rapidly progressive-GN (RPGN), 2 acute interstitial
nephritis (AIN), 5 on chronic dialysis. Baseline apoptosis was present in 1/22
(4.5%) of controls, 3/25 (12%) SLE, 2/6 (33.3%) RPGN and 10/19 (52.6%) MGN. A
significant decrease in CD3+CD8+ cell count and a significant increase of the
CD3+CD4/CD3+CD8+ ratio were found in apoptosis-positive subjects. DNA
fragmentation did not change after oral steroids, paralleling a 22 to 32%
decrease in total lymphocytes. Following intravenous methylprednisolone pulses, a
deeper drop of all lymphocyte subsets was observed, while DNA fragmentation
turned from present to absent in 2 MGN, but not in 2 RPGN, and from absent to
present in 1 ARF and 1 SLE, independently of the dosage. We demonstrated that the
presence of apoptosis in renal diseases is associated with decreased CD3+CD8+
cell count. Furthermore, steroid intravenous pulses, besides inducing a profound
decrease in lymphocyte subsets, do exert a dual effect on baseline leukocyte
apoptosis, eventually leading to a reversal of baseline patterns, either turning
from negative to positive or from positive to negative. Oral steroid therapy did
not influence baseline apoptosis.
PMID- 17026851
TI - Immunity to extracellular matrix antigens is associated with ultrastructural
alterations of the stroma and stratified epithelium basement membrane in the skin
of Hashimotos thyroiditis patients.
AB - Employing purified extracellular matrix (ECM) proteins, i.e. type I, III, IV and
V collagens (CI, CIII, CIV, CV), laminin (LM) and fibronectin (FN), as antigen
sources we detected autoantibodies to conformational and/or denatured ECM
antigens among 34 of 50 sera obtained from Hashimotos thyroiditis (HT) patients
and 6 of 51 control sera obtained from non-autoimmune thyroid disease patients
and healthy donors (HT sera vs. control sera p=4 x 10-9). Reactivity to
conformational antigens, mostly due to autoantibodies of the IgG isotype, was
observed in 30/50 HT sera and in 6/51 control sera (p=3.5 x 10-7) and was not
always concomitant with that to linear antigens, found in 23/50 HT and in 6/51
control sera (p=1.6 x 10-4). Ultrastructural analysis of skin biopsies obtained
from 18 HT patients without symptomatic cutaneous diseases revealed defects of
the stratified squamous epithelium basement membrane in 11/18, alterations of the
stroma in 13/18 and both basement membrane and stromal defects in 9/18.
Interestingly, 13/13 (p=0.012) and 9/11 (p=0.012) patients with stromal and
basement membrane defects respectively, exhibited serum antibodies to at least
one ECM antigen involved in the organization of the altered tissue compartment.
Lastly, 10/18 skin biopsies presented immunoglobulin (Ig) and/or complement (C3)
deposits along the cutaneous basement membrane zone (BMZ) or in the papillary
dermis and 9/10 sera from the same patients simultaneously showed antibodies to
at least one ECM antigen involved in the organization of these two skin
compartments. Besides, 8/11 HT patients with basement membrane defects exhibited
Ig or C3 deposits along the BMZ. Our findings suggest that autoantibodies to ECM
molecules might contribute to the development of asymptomatic extra-thyroid skin
diseases in HT patients.
PMID- 17026852
TI - Genetic analysis of oral squamous cell carcinoma by cDNA microarrays focused
apoptotic pathway.
AB - We investigated mRNA expression of the genes involved in the apoptotic mechanism
in oral squamous cell carcinoma (OSCC) by cDNA microarray. The aim of this study
was to identify genes mainly involved in tumorigenesis, comparing the difference
of gene expression in neoplastic and non-neoplastic tissues. Eight frozen samples
of OSCC and the corresponding normal oral mucosa were treated to obtain mRNA. The
mRNA extracted from these specimens was converted into cDNA and analyzed with
SuperArray GEArray Q Series Human Apoptosis Gene Array kit. Our results showed
that in OSCC there is a different expression of CRADD, FADD, ATM and APAF-1 genes
compared to normal mucosa. Real-Time PCR, and Western blot analysis were
performed on a separate cohort of patients in order to confirm the results
obtained by DNA microarray. Our analysis of apoptotic process through microarray
technology confirmed that different molecules could be responsible or favour the
imbalance of apoptosis in cancer tissues. Microarray technology has made it
possible to analyze the expression of multiple genes in a single experiment.
However, most commercial array kits, designed to include as many genes as
possible, produce a vast amount of data that often is difficult to interpret. In
addition, the cost of equipment is often prohibitive. In contrast, the focused
kit used was a complete, affordable and effective method to improve knowledge of
molecular specific pathways.
PMID- 17026853
TI - The role of calcium and magnesium ions in uptake of beta-amyloid peptides by
microglial cells.
AB - Amyloid peptides 1-40 and 1-42 (Abeta 1-40 and Abeta 1-42) are major components
of diffuse and neuritic senile plaques present in the brain of patients with
Alzheimers disease. Their interaction with microglial cells was studied using a
system partly mimicking these plaques, which consisted in heat-killed yeast
particles coated with either Abeta 1-40 or Abeta 1-42. Using these particles, it
has been shown in our laboratory that LRP is involved mainly in the elimination
of Abeta 1-42-coated heat-killed yeast particles and partly in that of Abeta 1-40
coated heat-killed yeast particles by microglial cells in culture. We show here
that in the presence of calcium and magnesium ions extracellular chelators,
namely EDTA (for both ions) and EGTA (for calcium ions), the internalization of
coated heat-killed particles was impaired. In the presence of BAPTA-AM, an
intracellular chelator of calcium ions and thapsigargin, an inhibitor of the
endoplasmic reticulum calcium pump, no effect was observed on the phagocytosis of
Abeta 1-40-coated heat-killed yeast particles, whereas that of Abeta 1-42-coated
heat-killed yeast particles was affected. These results suggest that different
signaling mechanisms are involved after the internalization of Abeta 1-40 and
Abeta 1-42.
PMID- 17026854
TI - Neonatal eating epilepsy: pathophysiological and pharmacologic aspects.
AB - We report a case of neonatal Eating Epilepsy. The baby was admitted to the
Neonatal Intensive Care Unit of Chieti after delivery, with respiratory distress
syndrome. In the first day of life the baby had an episode of arterial
desaturation and cyanosis with EEG alterations. After laboratory and instrumental
investigations we found a correlation between EEG abnormalities and GER. So we
administered a combination of anticonvulsive and antacid therapy and, considering
the total improvement of EEG, we diagnosed a neonatal form of "eating epilepsy".
PMID- 17026856
TI - Study of the morphology and biomechanics of sacral fracture.
AB - OBJECTIVE: To observe the morphological characteristics of sacral fracture under
different impact loads. METHOD: Ten fresh pelvic specimens were loaded in dynamic
or static state. A series of mechanical parameters including the pressure strain
and velocity were recorded. Morphological characteristics were observed under
scanning electron microscope. RESULTS: The form of sacral fracture was related to
the impact energy. Under low energy impact loads, ilium fracture, acetabulum
fracture and crista iliaca fracture were found. Under high energy impact loads,
three types of sacral fracture occurred according to the classification of Denis:
sacral ala fracture, Type I fracture; sacral foramen cataclasm fracture, Type II
fracture; central vertebral canal fracture, Type III fracture. Nerve injury of
one or two sides was involved in all three types of sacral fracture. The fracture
mechanism of sacrum between the dynamic impact and static compression was
significantly different. When the impact energy was above 25 J, sacral foramen
cataclasm fracture occurred, involving nerve root injury. When it was below 20 J,
ilium and sacral fracture was most likely to occur. When it was 20 approximately
25 J, Type I fracture would occur. While in the static test, most of the fracture
belonged to ilium or acetabulum fracture. The cross section of sacrum was crackly
and the bone board of Haversian system was brittle, which could lead to
separation of bone boards and malposition of a few of cross bone boards.
CONCLUSIONS: In dynamic state, sacrum fracture mostly belongs to Type I and Type
II, and usually involves the nerve roots. Sacrum fracture is relevant to the
microstructures, the distribution of the bone trabecula, the osseous lacuna and
the Haversian system of sacrum. The fracture of ilium and acetabulum more
frequently appears in static state, with slight wound of peripheral tissues.
PMID- 17026855
TI - TIMP-1 is a key factor of fibrogenic response to bleomycin in mouse lung.
AB - Pulmonary fibrosis is characterized by the excessive deposition of extracellular
matrix in the interstitium, resulting in respiratory failure. The role of
remodeling mediators such as metalloproteinases (MMPs) and their inhibitors
(TIMPs) in the fibrogenic process remains misunderstood. We investigated MMP-9,
MMP-2, TIMP-1, TIMP-2 and TIMP-3 in the fibrotic response to bleomycin of
fibrosis prone C57BL/6J and fibrosis resistant BALB/c mice. Mice were
administered with 0.1 mg bleomycin by intranasal administration. Either 24 h or
14 days after, the mice were anesthetized and underwent either bronchoalveolear
lavage (BAL) or lung removal. Collagen deposition in lung tissue was determined
by hydroxyproline measurement, MMP activity was analyzed by zymography, and other
mediators were analyzed by ELISA. TIMP-1 was localized in lung sections by
immunohistochemistry and real time PCR was performed to gene expression in lung.
Non parametric Mann-Whitney and Spearman tests were used for statistical
analysis. Fourteen days after bleomycin administration, hydroxyproline assay and
histological study revealed that BALB/c mice developed significantly less
fibrosis compared to C57BL/6J mice. At day 1, bleomycin enhanced TIMP-1, MMP-2
and MMP-9 protein levels in BALF, and induced corresponding genes in lung tissue
of both strains. The rise of Timp-1, Mmp-9 and Mmp-2 gene levels were
significantly stronger in lungs of C57BL/6J, whereas gelatinase activities of MMP
2 and MMP-9 were similar. Immunohistochemistry revealed that TIMP-1 macrophages
and epithelial cells were prominent TIMP-1 producers in both strains. At day 14,
neither MMP-2 nor MMP-9 levels exhibited strain-dependent protein level or gene
expression, although TIMP-1 was strongly associated with fibrosis. Interestingly,
bleomycin induced neither Timp-2 nor Timp-3 in lung tissue at any time of the
study. The present study shows that early altered regulation of TIMP-1 following
bleomycin administration may be involved in bleomycin-induced pulmonary fibrosis.
PMID- 17026857
TI - Repairing articular cartilage defects with tissue-engineering cartilage in
rabbits.
AB - OBJECTIVE: To investigate the effect of cancellous bone matrix gelatin (BMG)
engineered with allogeneic chondrocytes in repairing articular cartilage defects
in rabbits. METHODS: Chondrocytes were seeded onto three-dimensional cancellous
BMG and cultured in vitro for 12 days to prepare BMG-chondrocyte complexes. Under
anesthesia with 2.5% pentobarbital sodium (1 ml/kg body weight), articular
cartilage defects were made on the right knee joints of 38 healthy New Zealand
white rabbits (regardless of sex, aged 4-5 months and weighing 2.5-3 kg) and the
defects were then treated with 2.5% trypsin. Then BMG-chondrocyte complex (Group
A, n=18), BMG (Group B, n=10), and nothing (Group C, n=10) were implanted into
the cartilage defects, respectively. The repairing effects were assessed by
macroscopic, histologic, transmission electron microscopic (TEM) observation,
immunohistochemical examination and in situ hybridization detection,
respectively, at 2, 4, 8, 12 and 24 weeks after operation. RESULTS: Cancellous
BMG was degraded within 8 weeks after operation. In Group A, lymphocyte
infiltration was observed around the graft. At 24 weeks after operation, the
cartilage defects were repaired by cartilage tissues and the articular cartilage
and subchondral bone were soundly healed. Proteoglycan and type II collagen were
detected in the matrix of the repaired tissues by Safranin-O staining and
immunohistochemical staining, respectively. In situ hybridization proved gene
expression of type II collagen in the cytoplasm of chondrocytes in the repaired
tissues. TEM observation showed that chondrocytes and cartilage matrix in
repaired tissues were almost same as those in the normal articular cartilage. In
Group B, the defects were repaired by cartilage-fibrous tissues. In Group C, the
defects were repaired only by fibrous tissues. CONCLUSIONS: Cancellous BMG can be
regarded as the natural cell scaffolds for cartilage tissue engineering.
Articular cartilage defects can be repaired by cancellous BMG engineered with
allogeneic chondrocytes. The nature of repaired tissues is closest to the normal
cartilage. Local administration of trypsin can promote the adherence of repaired
tissues to host tissues. Transplantation of allogeneic chondrocytes has
immunogenicity, but the immune reaction is weak.
PMID- 17026858
TI - Treatment of chronic osteomyelitis with one-stage allograft.
AB - OBJECTIVE: To avoid disadvantages of two-stage cancellus bone autograft, we
investigated the feasibility of one-stage allograft for reconstructing the bone
defect resulting from debridement of chronic osteomyelitis in limbs. METHODS:
Between Feb. 1999 and Apr. 2004, 35 cases of chronic osteomyelitis (8 cases of
nonunion) underwent one-stage allograft after debridement in our hospital.
RESULTS: Thirty-five cases were followed up for an average period of 28 months
(range, 13 to 55 months), in which 32 cases (91.43%) were found no infection, and
3 cases (8.57%) were confirmed recurrence of infection. Four out of 8 cases of
bone nonunion healed in 9.5 months on average (range, 3 to 12 months), and
another case also acquired union after redebridement and autograft of ilium due
to infection recurrence 35 days after surgery. Renonunion occurred in 3 cases, 2
out of whom healed after secondary operation with autograft. One case of
renonunion and 2 cases of infection recurrence refused further treatment.
CONCLUSIONS: A high rate of infection arrest can be attained when one-stage
allograft is used to reconstruct the bone defect of chronic osteomyelitis after
debridement in limbs. Therefore, chronic osteomyelitis should not be regarded as
a contraindication to one-stage allogeneic bone grafting. Renonuion, however,
achieves a relatively high rate, especially in cases of segmental bone defect.
PMID- 17026859
TI - Bcl-2 gene therapy for apoptosis following traumatic brain injury.
AB - OBJECTIVE: To investigate the therapeutic effect of Bcl-2 fusion protein on
apoptosis in brain following traumatic brain injury. METHODS: Bcl-2 gene was
cloned by RT-PCR. Bcl-2 and EGFP genes were linked together and inserted into
pAdeno-X vector. This recombinant vector was packaged into infectious adenovirus
in HEK293 cells. Ninety Wistar rats were assigned randomly into experimental
group (n=45) and control group (n=45). All rats were subjected to traumatic brain
injury. Then recombinant adenovirus (for experimental group) or saline (for
control group) was injected into the traumatic brain. The expression of Bcl-2
fusion protein was investigated by Western blotting, immunohistochemistry and
fluorescence microscopy. Apoptosis in the injured brain was studied by TUNEL.
Animals' behavior capacity was evaluated by tiltboard test. RESULTS: In the
experimental group, many fluorescent cells were found around the traumatic locus,
which were also proven to be Bcl-2 positive by immunohistochemistry. On the
contrary, few Bcl-2 positive cells and no fluorescent cell were detected in the
control group. Bcl-2 expression of experimental group was much higher than that
of control group, which was illustrated by Western blotting. The apoptosis index
of experimental group was 0.027+/-0.005, and that of control group was 0.141+/
0.025 (P < 0.01). Two weeks after injury, animals of the experimental group
behaved better than those of the control group. CONCLUSIONS: A recombinant
adenovirus vector expressing Bcl-2 fusion protein has been constructed. Bcl-2
fusion protein can suppress apoptosis and promote cell survival. Moreover, the
behavior recovery of the injured animal is promoted. Bcl-2 fusion protein
provides a way to track the target cells in vivo.
PMID- 17026860
TI - Clinical analysis of hydroxyapatite orbital implantation after ocular trauma in
211 cases.
AB - OBJECTIVE: To evaluate the therapeutic effects and complications of
hydroxyapatite (HA) orbital implantation on patients after trauma-related
surgeries. METHODS: Retrospective analysis was made from 211 cases (211 eyes) who
underwent HA orbital implant placement after trauma-related enucleation or
evisceration, including 68 cases of evisceration and primary HA implant
placement, 77 cases of enucleation and HA implant placement wrapped with multi
windowed sclera, 66 cases of enucleation and HA implant placement free of
wrapping. All the cases were followed up for 1-5 years to observe the therapeutic
effects and major complications. RESULTS: Five of 211 cases had wound dehiscence.
Ten cases had HA implants exposure, including 1 case suffering severe orbital
infection and requiring HA implant removal. The implants exposure incidences by
the three surgical methods were from 1.30% to 10.06% and averaged 4.74%.
Significant difference was found in late exposure incidence and total incidence
from the three methods (chi(2)=13.372, P < 0.01 and chi(2)=7.540, P < 0.05). Two
cases had shrinkage of the lower fornix. Enophthalmos occurred in 1 case treated
by method 1 and was corrected by implanting porous polyethylene (Medpor) plate
into the bottom of orbit. In 210 cases, the artificial eye moved well and the
cosmetic results were satisfactory. CONCLUSIONS: Different surgical methods have
their own merit and disadvantage. Enucleation and placement of HA implant wrapped
with multi-windowed sclera has corroborated fewer complications than others.
PMID- 17026861
TI - Biomechanical and clinical study on screw hook fixation after direct repair of
lumbar spondylolysis.
AB - OBJECTIVE: To evaluate the biomechanical effect and clinical results of hook
screw fixation after direct repair of lumbar spondylous defects in the pars
interarticularis. METHODS: L(2)-L(6) spines of 8 fresh-frozen and thawed calf
cadavers were used for mechanical testing. Bilateral spondylous defects were
created in the L(4)vertebra. The intervertebral rotation ranges between L(4) and
L(5) were scanned and computerized in various states of motion, such as
flexion/extension, lateral bending and torsional loadings applied on the intact
spine and the spondylous spine when the spondylous spine was fixed with modified
Scott's fixation, hook screw fixation and Buck's fixation sequentially and
respectively. Between July 2002 and February 2004, 14 young male patients (aged
15-31 years) suffering from symptomatic lumbar spondylolysis were treated with
TSRH hook screw fixation after direct repair of the defects. MacNab criteria were
used to assess their pre-and post-operative status. RESULTS: Each fixation
technique could significantly increase the intervertebral rotational stiffness
and made the stiffness return to nearly the intact level. Hook screw technique
provided more rotational stability than the others. Hook screw and Buck's
techniques provided more flexion/extension stability than modified Scott's
technique. Neither complication nor instrumental failure was observed in this
study. The mean follow-up period was 21 months. All the patients except one
acquired union during the follow-up period. Thirteen patients had a "good" or
"excellent" result according to MacNab criteria. CONCLUSIONS: Hook screw fixation
shows biomechanical advantages and is safe and effective for young patients with
lumbar spondylolysis.
PMID- 17026862
TI - Gene damages of mitochondrial DNA encoding cytochrome oxidase of intestinal
epithelial cells in hemorrhagic shock rats.
AB - OBJECTIVE: To investigate the detrimental effects of hemorrhagic shock on the
structure and function of mitochondria DNA (mtDNA) encoding cytochrome oxidase
genes in intestinal epithelial cells. METHODS: Wistar rats were used and divided
into two groups: hemorrhagic shock group and control group. Hemorrhagic shock
model of rats was utilized in this experiment. The mtDNA was extracted from the
intestinal epithelial cells and amplified by polymerase chain reaction (PCR) with
different primers of cytochrome oxidase (COX I, COX II and COX III). The products
of PCR were directly sequenced. RESULTS: Hemorrhagic shock could result in the
point mutagenesis in mitochondrial genome encoding cytochrome oxidase (COX I and
COX II). There were 4, 4, 22, 16, 35 point mutations in COX I from 5545 to 6838
bp in 5 shocked rats. There were five point mutations in COX II from 7191 to 7542
bp at the site of t7191c, t7212c, a7386g, a7483g, c7542g in 1 shocked rat. There
was no mutation found in COX III. CONCLUSIONS: Hemorrhagic shock could
significantly induce the damage of the gene of cytochrome oxidase encoded by
mtDNA.
PMID- 17026863
TI - Repair of the radial defect of rabbit with polyester/tricalcium phosphate
scaffolds prepared by rapid prototyping technology.
AB - OBJECTIVE: To evaluate the effects of repairing rabbit radial defects with
polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology
loaded with bovine bone morphogenetic protein (bBMP), and find new carriers for
growth factors. METHODS: Polyester/tricalcium phosphate scaffolds prepared by
rapid prototyping technology loaded with and without bovine BMP were used to
repair the 15 mm radial defect in rabbit. Then the results of radiography,
histology, scaffolds degrade rates and bone mineral density (BMD) were appraised
to examine the effects at the 12th week. RESULTS: At the 12th week
postoperatively, all defects treated with bBMP were radiographically repaired. No
radius implanted polyester/tricalcium phosphate scaffolds without bBMP showed
radiographic and histological union. At experimental groups, longitudinal
alignment of lamellar structure was observed histologically at the 12th week,
indicating that remodeling of regenerated bone was complete in different degree.
Of the three experimental groups, the bony regeneration and remodeling of callus
in poly lactide-co-glycolide/tricalcium phosphate (PLGA/TCP) group was the best.
The BMD values were beyond 70% of normal value at the 12th week while the
PLGA/TCP scaffolds group was the highest, and no abnormalities were observed in
the surrounding soft tissue in all groups. CONCLUSIONS: Polyester/tricalcium
phosphate scaffolds prepared by rapid prototyping technology loaded with bovine
BMP can repair a 15 mm radial defect of rabbit. As for the results, the PLGA/TCP
scaffold is ideal and better than poly L-lactide-co-D, L-lactide (PDLLA/TCP)
scaffold, but the ploy L-lactic acid (PLLA/TCP) is not so good for its low
degradation rates.
PMID- 17026864
TI - Antioxidation of quercetin against spinal cord injury in rats.
AB - OBJECTIVE: To observe the effect of quercetin on experimental spinal cord injury
(SCI) in rats. METHODS: Sixty Sprague-Dawley rats were randomly divided into four
groups: Group A only for laminectomy, Group B for laminectomy with SCI, Group C
for SCI and intraperitoneal injection with a bolus of 200 mg/kg quercetin and
Group D for SCI and intraperitoneal injection of saline. SCI model was made by
using modified Allen's method on T(12). Six rats of each group were killed at 4 h
after injury and the levels of free iron and malondialdehyde (MDA) of the
involved spinal cord segments were measured by bleomycin and thiobarbituric acid
(TBA) assays separately. The recovery of hind limb function was assessed by
Modified Tarlov's scale and inclined plane method at 7 d, 14 d and 21 d after
SCI. The histological changes of the damaged spinal cord were also examined at 7
d after SCI. RESULTS: After SCI, the levels of free iron and MDA were
significantly increased in Groups B and D, while not in Group C. The Modified
Tarlov's score and the inclined plane angles were significantly decreased in
Groups B, C and D. The histological findings were not improved. CONCLUSIONS:
After SCI, quercetin can reduce the level of lipid peroxidation, but not improve
recovery of function.
PMID- 17026865
TI - Progress of cellular dedifferentiation research.
AB - Differentiation, the stepwise specialization of cells, and transdifferentiation,
the apparent switching of one cell type into another, capture much of the stem
cell spotlight. But dedifferentiation, the developmental reversal of a cell
before it reinvents itself, is an important process too. In multicellular
organisms, cellular dedifferentiation is the major process underlying
totipotency, regeneration and formation of new stem cell lineages. In humans,
dedifferentiation is often associated with carcinogenesis. The study of cellular
dedifferentiation in animals, particularly early events related to cell fate
switch and determination, is limited by the lack of a suitable, convenient
experimental system. The classic example of dedifferentiation is limb and tail
regeneration in urodele amphibians, such as salamanders. Recently, several
investigators have shown that certain mammalian cell types can be induced to
dedifferentiate to progenitor cells when stimulated with the appropriate signals
or materials. These discoveries open the possibility that researchers might
enhance the endogenous regenerative capacity of mammals by inducing cellular
dedifferentiation in vivo.
PMID- 17026866
TI - Clinical significance of scoring system for systemic inflammatory response
syndrome.
AB - The concepts of systemic inflammatory response syndrome (SIRS) and scoring system
were defined by the journal of Bone in 1992. SIRS was described as occurrence of
two or more clinical criteria in four ones (fever or hypothermia, tachypnea,
tachycardia, and leukocytosis). An early diagnosis and estimation of systemic
inflammation in patients is helpful for treatment selection. This paper reviews
the application of SIRS scoring system, which has been extensively validated for
large groups of critical care patients with severe injury and critical surgical
diseases. Recent studies have documented SIRS score as a significant predictive
parameter of adverse outcome in critical care patients. Furthermore, some studies
also give us a suggestion on how to reduce the overload systemic response.
PMID- 17026867
TI - Atopic eczema.
PMID- 17026871
TI - Evidence-based allergy diagnostic tests.
AB - Effective management of allergic diseases relies on the ability to make an
accurate diagnosis. Although clinicians rely on experience obtained over many
years of practice, such experience is anecdotal and unique to the individual
using it. The result is a tendency for patients with similar clinical
presentations to receive different diagnoses and treatment, depending on which
provider they happened to see. The probability that a patient has a particular
diagnosis can be determined using a combination of diagnostic tests. To make the
best use of tests, it is important to understand their performance
characteristics in terms of reproducibility and likelihood ratios. A test that is
reproducible but that does not predict the presence of a disease is not helpful,
nor is an accurate test that is not reproducible. To improve the reproducibility
of diagnostic tests, it is important that proficiency testing be instituted for
both skin and in vitro tests so that the coefficient of variance can be
determined. This has already been done for the latter and needs to be done for
skin tests as well. With use of a combination of history and appropriate
diagnostic tests, the probability that a particular diagnosis is present can be
increased or decreased sufficiently either to confirm it or to rule it out. As
proficiency testing of allergy tests becomes more common and the use of tests
becomes more consistent, we believe that patients with allergic diseases will
benefit.
PMID- 17026872
TI - Childhood asthma in the emergency department: trends, challenges, and
opportunities.
AB - Acute exacerbations of childhood asthma are frequently managed in the emergency
department (ED). ED-based surveillance and intervention projects highlight the
limitations and challenges of acute and chronic childhood asthma management.
Because a significant number of asthmatic children currently receive and will
likely continue to seek acute asthma care in the ED, provision of asthma
education and initiation of controller medication therapy during the ED visit,
although controversial, may contribute to improving asthma outcomes and
eventually to reducing the burden of asthma on our overcrowded EDs.
PMID- 17026874
TI - Eosinophilic disorders in children.
AB - Many pediatric diseases demonstrate blood or tissue eosinophilia. Included among
these disorders are common atopic diatheses such as asthma as well as the rarer
conditions of hypereosinophilic syndrome and eosinophilic gastrointestinal
disorders. Eosinophil trafficking and activation in target organs leads to tissue
damage and ongoing reparative attempts that can ultimately result in changes in
organ structure and function. Recent treatment with biologic agents such as
tyrosine kinase inhibitors and anti-interleukin-5 has offered new therapeutic
options in certain eosinophilic disorders. Eosinophilic disorders such as
eosinophilic esophagitis are increasingly being diagnosed in children, but many
lessons in disease pathogenesis, diagnosis, optimal treatment, and natural
history continue to be learned.
PMID- 17026873
TI - Immunodeficiency in childhood.
AB - Primary immunodeficiency disorders (PIDs) continue to illuminate mechanisms of
human immunity and hypersensitivity. New discoveries in common variable
immunodeficiency, the most enigmatic of PID syndromes, reveal molecular pathways
of importance in human antibody production. FOXP3 mutations demonstrate the
essential role that T-regulatory cells play in controlling autoantibody formation
and disease. Interleukin-1 receptor-associated kinase 4 deficiency emphasizes the
key role that innate immunity plays in the defense of bacterial disease occurring
early in life. With respect to therapy, subcutaneous immunoglobulin treatment may
indeed be a better treatment than intravenous immunoglobulin for many patients
with antibody deficiency. Finally, PIDs remain in the vanguard for the treatment
of inherited disorders by gene therapy. Gene therapy has cured patients with
chronic granulomatous disease and severe combined immunodeficiency, but not
without morbidity and mortality. Into the 21st century, PIDs continue to instruct
us in human health and disease.
PMID- 17026876
TI - Advances in imaging of the paranasal sinuses.
AB - Imaging technology has played a significant role in the diagnosis and management
of sinonasal disorders. Plain sinus films are almost exclusively replaced by CT
in the work-up for inflammatory sinus disease. MRI provides complementary
information to CT in cases of sinonasal and skull-base neoplasms. The evolution
of endoscopic surgical techniques for the paranasal sinuses and skull base is
made possible by the parallel advancement of imaging technologies. Recent
advances that are currently in clinical use have included multidetector row CT
scanners and computer image-guidance systems for surgery. Three-dimensional CT
angiography, image-guided CT-MR fusion, and intraoperative image-guidance are new
techniques that are currently being evaluated. As imaging technology continues to
advance, so does the capability to treat diseases beyond the sinuses and skull
base with minimally invasive, endoscopic approaches.
PMID- 17026875
TI - The relationship between rhinosinusitis and asthma sinusitis.
AB - Chronic sinusitis comprises numerous disorders characterized by inflammation,
mucous gland hyperplasia, and remodeling. Chronic hyperplastic eosinophilic
sinusitis (CHES) is characterized by unrestrained proliferation of eosinophils,
Th2-like lymphocytes, fibroblasts, goblet cells, and mast cells. The pathology of
CHES is similar to that of asthma, and it is frequently diagnosed in association
with asthma. It has been reported that exacerbations of CHES occur temporally
with worsening of asthma; however, in the absence of well-controlled studies,
this linkage remains unproven. In this article, the potential mechanisms linking
these two diseases are examined.
PMID- 17026877
TI - Rhinosinusitis in children.
AB - Clinical practice guidelines for the management of acute bacterial rhinosinusitis
in children were published by the American Academy of Pediatrics in 2001. Changes
in the antibiotic susceptibility patterns for the common pathogens causing both
acute and chronic rhinosinusitis warrant a reevaluation and update of these
recommendations. In addition, there was only a very brief discussion of chronic
disease in this publication, with the conclusion that the pathogenesis and
management of recurrent or prolonged infection were essentially unknown. Although
there are still insufficient data in the literature to develop evidence-based
clinical guidelines, a careful review of recent literature and the clinical
experience of experts who manage pediatric chronic sinusitis are presented in an
effort to provide some specific recommendations and to offer practical treatment
options. Factors associated with chronic rhinosinusitis should be addressed
individually and include environmental pollution, recurrent viral upper
respiratory infections, allergic and nonallergic rhinitis, ciliary dyskinesia,
cystic fibrosis, immunodeficiency, gastroesophageal reflux, and anatomic
abnormalities.
PMID- 17026878
TI - Primary ciliary dyskinesia and upper airway diseases.
AB - Primary ciliary dyskinesia (PCD) is a rare and difficult-to-diagnose disease with
morbidity related to infections of the upper and lower respiratory tract. The
disease is caused by mutations in genes that are required for proper ciliary
function. The defect in ciliary function results in reduced or absent mucociliary
clearance, thereby predisposing the affected individual to repeated bacterial
infections. Recent advances in the understanding of the basic biology and
function of the cilium have led to the identification of some of the genes that
are mutated in cases of PCD. Further studies of this disease will likely lead to
earlier diagnosis, better treatment, and improved outcomes.
PMID- 17026879
TI - Dust mite allergen avoidance as a preventive and therapeutic strategy.
AB - Asthma is a global health problem with genetic and environmental components.
Indoor allergens have a major impact on asthma, and exposure in sensitized
subjects can compromise lung function. A reduction in allergen exposure would
seem a logical facet to treatment. Methods for reducing mite allergen levels that
are effective in the laboratory may not work in the home and may not result in a
clinical benefit. Six ongoing studies are investigating the effects of
environmental control on the primary prevention of asthma and allergies. Although
the Isle of Wight and Canadian studies provide encouraging results at age 8 and 7
years, respectively, it will be some time before a definitive public health
message emerges. For secondary prevention, there is little evidence to support
the use of mite-proof encasings as a single intervention in adults. In children,
however, single or multifaceted interventions appear to be of some benefit.
PMID- 17026880
TI - Principles and clinical application of the locking compression plate (LCP).
AB - The principle of the locking compression plate (LCP) is represented by the
combination of two completely different anchorage technologies and two opposed
principles of osteosynthesis in one implant it combines the principles of
conventional plate osteosynthesis for direct anatomical reduction with those of
bridging plate osteosynthesis. Since the LCP can be used as a conventional plate
using only dynamic compression, as a pure internal fixator using locking head
screws, or as both combined, it provides the surgeon with multiple variations.
Nevertheless, these new possibilities mean that preoperative planning and an
understanding of the different biomechanical principles of osteosynthesis are
essential if good clinical outcomes are to be achieved and maximum benefit is to
be attained from the options offered by the LCP system. The current article
provides biomechanical background to and guidelines for the use of LC plates in
the operative treatment of fractures and also reports experimental and clinical
results obtained with LCP.
PMID- 17026881
TI - [Current strategies for prevention of prosthetic joint infection].
AB - Deep sepsis still remains the second most common cause of prosthetic joint
failure despite its overall incidence is decreasing. It can be defined as a
bacterial growth and replication on the prosthetic joint surface resulting in
periprosthetic tissue damage and prosthesis loosening. The implants are colonized
by airborne-, skin-, tool-, and/ or surgeon-related bacteria during surgery even
though majority of procedures are performed under strictly respected conditions
nowadays. After the insertion of the prosthesis into the human body the race
between bacteria and host cells begins on what will colonize the prosthetic
surface first. If the bacteria are more successful then they develop on formation
of biofilm which is the biological correlative for the prosthetic joint infection
(PJI) resisting effectively against host immune response and antibiotics. That is
why preventative measures are strongly worth to do it, and removal of the
prosthesis is the single optimal treatment. Each step in the pathogenesis of
prosthetic joint infection may represent relevant targets against which
prevention strategies may be directed. Of them the most useful seems to be
identification of individual factors predisposing for PJI development, antibiotic
prophylaxis given before the surgery, and operating room/ surgical quality
parameters. Key words: prevention, prosthetic joint infection, deep sepsis,
biofilm, total joint replacement.
PMID- 17026882
TI - Acute musculoskeletal infection: comparison of different methods for
intraoperative bacterial identification.
AB - PURPOSE OF THE STUDY: Various techniques are used for detection of pathogens in
musculoskeletal infection. These methods differ with respect to reliability and
ease of handling. A prospective study was performed to evaluate the efficacy of
three intraoperative techniques. MATERIAL AND METHODS: In 20 cases (18 patients)
with clinically confirmed acute musculoskeletal infections, intraoperative
collected swab samples, tissue samples and fluid samples injected into standard
blood culture vials were used for microbiological diagnosis. Identification of
bacteria, time necessary for detection and ease of handling during surgery was
evaluated. RESULTS: In 19 cases bacterial growth was demonstrated using either
intraoperative swabs or blood culture technique (95% sensitivity), whereas 18
tissue biopsies were positive (90% sensitivity. 27 bacterial species were
isolated. In 18 instances for the swab technique, 14 instances for the tissue
biopsy and 4 operations for the blood culture vials, ease of handling was rated
as excellent. DISCUSSION: The study demonstrated differences between the three
tested methods with respect to ease of handling. With respect to the number of
detected organisms and time for their detection there are no significant
differences. These last findings are in contrast to of the results of other
authors. The reason for this could be that during operative dissection an
accurate and specific collection of specimens from the acute deep infected soft
tissues and bones independent from the type of surgical procedure is possible.
Therefore, even with the swab method a high amount of microorganisms can be
recovered. Especially for intraarticular infections, fluid samples injected into
standard blood vials is a practical method for the surgeon. In acute
musculoskeletal infections other than joint infections, there is less benefit for
the blood culture vials. CONCLUSION: Intraoperative swab technique yields valid
results comparable to other techniques and is an accurate technique for detection
of pathogens from acute musculoskeletal infections. Key words: implant,
infections, bacteriological techniques, comparative study.
PMID- 17026883
TI - [Method for assessment of distribution of UHMWPE wear particles in periprosthetic
tissues in total hip arthroplasty].
AB - PURPOSE OF THE STUDY: Aseptic loosening of implants is the main complication
affecting the longevity of joint prostheses. The highest proportion of loosening
occurs due to osteolysis produced by the presence of ultra-high molecular weight
polyethylene (UHMWPE) wear particles smaller than 1 microm. These can be
identified by microscopic, spectroscopic or light-scattering methods. Here we
describe our method for counting wear particles, based on the principle of light
scattering. MATERIAL AND METHODS: Between 2002 and 2004, we collected samples of
polyethylene granuloma in 19 patients who underwent revision total hip
arthroplasty (THA) for aseptic loosening. The samples were obtained from strictly
defined areas corresponding to the radiographic presentation of periprosthetic
zones describes by Gruen and DeLee in THA. The frozen samples were lyophilized
and subjected to delipidation and hydrolyzation procedures in 65 % HNO3. The top
part of solution containing wear particles was blended with isopropanol, and the
mixture was filtered through a 10-microm polycarbon membrane. Subsequently, the
filtrate was filtered through a 0.1-microm membrane. Membranes with trapped
particles, 0.1 to 1.0 microm in size, were sent for particle characterization and
quantification. The number of wear particles was measured by the method based on
light scattering with calibration (LSC), using a Beckman Coulter LS230 analyzer
that can express particle size distribution in a given volume in percent. The
method was based on the fact that each particle reflects rays that can be
measured. The medium measured contained an unknown number of UHMWPE particles and
a known number of calibration glass beads varying in size. The number of UHMWPE
particles was calculated from the known number of calibration beads. RESULTS:
Because the collected samples were also used to develop the method, comprehensive
data was obtained in six patients only. Particle distribution recorded in the
periprosthetic zones in THA varied greatly; up to a five-fold difference in
particle concentration was observed between the zones. In five of the six
patients, the highest particle concentration was found in zone III. DISCUSSION:
Seeking a method that would be exact, quick and cheap and would eliminate
particle aggregation remains the subject of study for researchers cooperating
with clinical practice. At present methods based on weighing isolated particles
are used most frequently. We developed the LSC method that, for quantification,
utilizes the ability of particles to disperse light, and allows us to calculate
the real numbers of UHMWPE wear particles in a medium containing a known number
of calibration particles. Although this is an indirect method, it gives more
accurate results than the direct weighing of particles. The advantages of the LSC
method involve less demand on sample purity, greater speed and low limits of
detection. The method is useful for statistical evaluation of a larger number of
samples. The variation in particle distribution in THA found in this study is in
agreement with the relevant literature data; it is also in agreement with our
assumptions and clinical findings. CONCLUSIONS: The authors developed an original
method for assessment of UHMWPE wear particles in tissue samples, which is
quicker than the methods so far used. In the periprosthetic tissues studied,
particles about 1 microm in size were detected; their numbers (about 1010
particles per gram dry tissue) are in agreement with the literature data. The
distribution of particles in periprosthetic zones in THA was uneven. The highest
number of particles was found in the neighboring zone III and zone 7, as
described by Gruen and DeLee. Key words: wear, polyethylene, total hip
arthroplasty, light scattering, aseptic loosening, wear particles.
PMID- 17026884
TI - [Treatment of deep cartilage defects of the knee with autologous chondrocyte
transplantation on a hyaluronic Acid ester scaffolds (Hyalograft C)].
AB - PURPOSE OF THE STUDY: The treatment of chondral defects by transplantation of
autologous chondrocytes has recently shown further development. Various
biomaterials are used as carriers facilitating attachment and even distribution
of chondrocytes in the defect. Since 2003 Hyalograft C, hyaluronan-based
scaffolds, has been used, in a clinical study, for implantation of autologous
chondrocytes in the treatment of deep chondral lesions of the knee at our
department. MATERIAL: Eight patients (7 men and 1 woman; average age, 31 years)
followed up for at least 9 months were evaluated. The lesions with an average
size of 3.9 cm2 were localized on femoral condyles. METHODS: The outcome of
surgery was evaluated on the basis of the IKDC Subjective Knee Evaluation Form,
Knee Injury and Osteoarthritis Outcome Score (KOOS) and Lysholm knee score. The
patients underwent MR examination preoperatively and at 3, 6 and 12 months after
surgery. The newly-formed cartilage was assessed by International Cartilage
Repair Society (ICRS) visual scores at second-look arthroscopy carried out at 9
to 12 months following transplantation. Consistency of the new cartilage
developing in the defect and that of healthy cartilage around the defect was
compared by means of a special indentation probe in three patients. A biopsy
sample was collected from the grafted site for histological, histochemical and
immunohistochemical examination. RESULTS: All patients reported improvement in
knee function on average at 10 months after surgery. The average IKDC subjective
score increased from 46 points preoperatively to 74 points postoperatively. The
KOOS evaluation showed pain relief and improved function. In quality of life
evaluation the average score of 35 points before surgery increased to 70 points
after it. The average Lysholm knee score was 61 points before and 83 points after
surgery. MR findings correlated well with arthroscopic findings. Second-look
arthroscopy showed a normal appearance of the newly-formed cartilage in six, and
an abnormal appearance in two patients. The average ICRS visual score was 9.4
points. No graft failure was recorded. The newly-produced tissue had the
histological characteristics of a mixed hyaline and fibrous cartilage in seven
patients, and of hyaline-like cartilage in one patient. DISCUSSION: The ICRS
visual repair assessment of the newly-formed tissue showed that our results were
better than the one-year outcomes reported by Bartlett et al. (11 patients after
transplantation of a collagen bilayer seeded with chondrocytes), but worse than
the results of an Italian multi-center study (55 patients with Hyalograft C-based
grafts followed up on average for 14 months). At almost one year, implantation of
on a Hyalograft C resulted in the production of mixed cartilage incorporated well
in the subchondral bone. Only one patient had mature hyaline cartilage. One year
is too short to allow for complete remodeling of the newly formed cartilage into
a mature hyaline cartilage. This is in agreement with other studies suggesting
that the new cartilage continues to mature and remodel for a time longer than one
year. CONCLUSIONS: Based on our results we suggest that the use of Hyalograft C
is a safe and effective option for treatment of deep chondral defects of the
knee; it is particularly useful in patients in whom the primary defect treatment
has failed. The application of Haylograft C is relatively quick and easy; this is
convenient when surgery involves more than one procedure (ligament
reconstruction, osteotomy). However, a definite evaluation of this method will be
possible only after long-term results are available. Key words: deep cartilage
defects, chondral defects, cartilage repair, autologous chondrocyte
transplantation, hyaluronan- based scaffold, Hyalograft C, cartilage repair
assessment, ICRS.
PMID- 17026885
TI - [Complex injuries of the shoulder - floating shoulder].
AB - Complex injuries of the shoulder are comparatively rare. Within the field of
complex shoulder injuries this article particularly deals with the diagnosis and
therapy of the "floating shoulder injury" as a review article. This term
describes a discontinuation of the osseus and soft tissue suspension of the upper
extremity from the axial skeleton. By literature review and involvement of recent
biomechanical studies this article will show the injury patterns that lead to
instability of the shoulder girdle and the therapeutic to be employed in
respective cases. Key words: shoulder, floating shoulder, clavicle fracture,
scapula fracture.
PMID- 17026886
TI - [Hip joint arthroplasty following surgical treatment of acetabular fracture].
AB - PURPOSE OF THE STUDY: A group of 49 patients treated by total hip arthroplasty
after previous surgery for an acetabular fracture are evaluated in this
retrospective study. MATERIAL: In the period from 1997 to 2004, 49 patients, 35
men and 14 women, with posttraumatic arthritis following acetabular fracture were
treated in our department. The average age was 42 years, with 67 % of the
patients being younger than 40 years. The average follow-up was 42 montsh (range,
18 to 92). The acetabular fractures evaluated by the AO classification included
type A1 in 17 patients, type A2 in seven, type B1 in nine, type B2 in six, type
B3 in seven, type C1 in three and type C2 in two patients. METHODS: In 11
patients with aseptic necrosis of the femoral head without acetabular deformity,
cementless Zweymuller Bicon or Spotorno CLS acetabular components were used.
Twenty-nine patients with acetabular defects of type I and II, according to the
American Academy of Orthopedic Surgeons (AAOS) classification, underwent
acetabular reconstruction with the bone impaction grafting technique, using
allogenic grafts and cementless Zweymuller Bicon acetabular components. Four
patients with AAOS type III acetabular defects were treated with impacted
morsellized bone allografts, using titanium mesh and cemented polyethylene
acetabular cups. Three patients were treated with solid bone grafts fixed with
osteosynthetic material. In two patients with type IV defects, osteosynthesis
using a plate completed with allogenic bone graft, a mesh and a cemented cup were
used. RESULTS: The patients were evaluated with the use of Harris hip scores. In
20 patients (43 %) the outcomes were excellent, and very good in 18 (37 %),
satisfactory in six (12 %) and poor in four (8 %) patients. DISCUSSION: Hip joint
arthroplasty following the surgical treatment of acetabular fracture is indicated
in patients with post-traumatic hip arthritis. This frequently occurs due to
complications associated with surgery for acetabular fractures, or the cause
remains unknown. Some types of these fractures show a high proportion of poor
results. The group can be divided into two different subgroups: the patients with
a spherical, healed acetabulum and the patients with acetabular deformity or
defect, of which the most serious condition is pseudoarthrosis of one or both
columns. In the first subgroup, the surgical technique of acetabulum replacement
is the same as in cases with arthritis due to degenerative disease. In the other
subgroup, the procedure for cup implantation resembles revision arthroplasty for
acetabular loosening. The options for treating defects or deformities and the
implants used are identical in both situations. Therefore the results should be
compared with those of revision arthroplasty and not primary implantation. Scars,
fibrotic changes in muscles, para-articular ossification, bone defects, residual
deformities of the acetabulum, devitalized bone fragments or hindering previous
implants make the surgical procedure more difficult and interfere with good
results. CONCLUSIONS: Total hip arthroplasty carried out after acetabular
fracture is technically demanding. The prerequisite for a good result is to
achieve primary stability of the acetabulum. Acetabular reconstruction is based,
in the first place, on replacement of the missing bony tissue, and on providing
conditions for correct alignment of the acetabulum and reliable primary and early
secondary osteointegration. THA after acetabular fracture achieves poorer results
than when it is indicated for degenerative disease. Key words: acetabular
fracture, post-traumatic hip arthritis, total hip replacement.
PMID- 17026887
TI - [Early primary total hip arthroplasty for acetabular fractures in elderly
patients].
AB - PURPOSE OF THE STUDY: The aim of this pilot study was to evaluate the clinical
and functional outcomes of total hip arthroplasty (THA) in patients with
acetabular fractures due to a low-energy injury. Acute primary THA included an
antiprotrusion cage and autologous bone grafting of the acetabulum. This
prospective study was carried out between 1998 and 2004. MATERIAL: Ten patients,
of whom six were men, (average age, 71 years; range, 60 to 83 years) with
acetabular fractures were treated by THA. Two patients had type A2, two had type
B1, three had type B2 and three had type B3 fractures, as assessed by the AO
classification. X-ray showed osteoporosis due to decreased bone mass in all
patients, and dislocations of the fragments in the weight-bearing area of the
joint exceeded 1 cm. The average follow-up was 36 months. METHODS: Indications
for primary THA included, in addition to higher age, displacement in the fracture
line exceeding 1 cm, a fracture line extending to the weight-bearing part of the
acetabulum, presence of hip arthritis, cartilage injury, defects of the weight
bearing area of either the femoral head or acetabulum, and Pipkin type IV injury.
The interval between accident and surgery ranged from 6 to 12 days (average,
9.5). Three surgical techniques were used, namely, cemented THA with a
polyethylene cup cemented into an acetabulum-stabilizing cage; reconstruction
with a cementless RSC acetabular component; internal fixation using screws and a
cemented cup. Bone grafting of the acetabulum was used in all patients. Evaluated
were basic operative parameters, complications, X-ray findings, ability to walk
and Merle d'Aubigne scores. RESULTS: The average operative time was 100 min, the
average blood loss was 1000 ml. Hip motion showed the following average values:
flexion, 110 degrees ; extension, 10 degrees ; rotation, 30 degrees -0 degrees
30 degrees ; adduction, 25 degrees ; abduction, 35 degrees . All patients
returned to their preoperative range of motion. X-ray examination showed good
reduction, bone graft was completely incorporated in the acetabulum, and no
displacement or signs of loosening or graft migration were recorded. Two patients
had Brooker type I heterotropic ossification. The final evaluation of function at
36 months on the basis of the Merle d'Aubigne classification showed excellent and
good results in four (57 %) and three (43 %) patients, respectively. The
remaining three patients had a shorter follow-up, but were fully mobile with no
complications observed. DISCUSSION: It has been reported that bony union of
acetabular fracture after open reduction and internal fixation (ORIF) was
achieved in 74 % patients younger than 60 years, but in only 44 % of the patients
older than 60 years. Secondary THA following ORIF is a demanding technique. Due
to adhesions and a frequent malposition of the acetabulum, THA is associated with
and increased risk of infection, tendency to develop para-articular
ossifications, and a higher risk of early component loosening than in the
standard procedure. One of the options is to perform acetabular stabilization and
primary THA at one stage. The results of our study are fully in agreement with
those reported for THA in hip arthritis or dislocated fracture of the femoral
neck. CONCLUSIONS: Acute primary THA with the use of a antiprotrusion cage and
bone grafting for acetabular fractures in elderly patients allows us to employ
only one surgical technique for definitive repair. It provides primary stability
and immediate pain relief, permits graded weight-bearing and early pain-free
mobilization, and may also treat hip arthritis, if it exists. This technique has
also good prospects for a selected group of younger patients in whom the
treatment of acetabular fractures has a poor prognosis. Key words: acetabular
fracture, elderly patient, primary total hip arthroplasty.
PMID- 17026888
TI - [Cementless ceramic-on-ceramic total hip system].
AB - PURPOSE OF THE STUDY: This is an experimental and clinical study on the use of
cementless, ceramic-on-ceramic total hip arthroplasty (THA). MATERIAL AND
METHODS: In the experimental part, the authors constructed, by means of
mathematical analysis of finite elements, surface tension standards for the
ceramic liner at various angles of cup inclination, and identified potentials for
destruction of the liner. In the clinical trial, they evaluated the outcomes in
50 patients, out of the 249 implanted prostheses, at five-year follow-up.
RESULTS: The experiment showed that a slightly steeper inclination the cup
provided physical conditions for increased longevity of the ceramic liner. In the
clinical study, no post-operative complications, such as fracture of the
acetabulum or femur, and dislocation or break of any ceramic part, were recorded.
No infection or loosening of the prosthesis occurred. The patients did not
complained of any pain in the hip joint, which is typical of non-cemented THA.
DISCUSSION: Ceramic-on-ceramic bearing surfaces show the least wear due to high
biocompatibility. Computer-assisted surgery can markedly reduce the risk of
incorrect positioning of the acetabular component. In this prospective study, the
five-year survival of ceramic-on-ceramic THA in 50 patients free from any
complications, whose Harris hip score was 97.4 points, suggests that objections
to these prostheses, as raised by some authors, are not justified. CONCLUSIONS:
In our experience the Plasmacup Bicontact ceramic-on-ceramic prosthesis is one of
a few options that has a prospect of remaining the only total hip replacement in
one's lifetime. Key words: total hip replacement, ceramic-on-ceramic.
PMID- 17026889
TI - [Be careful on the Internet].
PMID- 17026890
TI - [Bleeding complications after treatment with antithrombotic agents after acute
coronary syndrome].
PMID- 17026891
TI - [Survival in cold water. Physiological consequences of accidental immersion in
cold water].
AB - This survey addresses the immediate physiological reactions to immersion in cold
water: cold shock response, diving reflex, cardiac arrhythmias and hypothermia.
Cold shock response is the initial sympathetic reaction to immersion in cold
water. The diving reflex is elicited by submersion of the face. Afferent and
efferent nerves are the trigeminal and vagal nerves. Cardiac arrhythmias occur
immediately after immersion. If the immersion persists, hypothermia becomes an
issue. Hypothermia is delayed by habituation to immersion in cold water as well
as insulating garments, subcutaneous fat and a large lean body mass.
PMID- 17026892
TI - [Therapeutic hypothermia after perinatal asphyxia--the time is ripe].
PMID- 17026893
TI - [Bivalirudin: a direct thrombin inhibitor in percutaneous coronary
interventions].
AB - Bivalirudin is a direct thrombin inhibitor that has biological and
pharmacokinetic advantages over heparin, e.g., by inhibiting both fibrin-bound
and -unbound thrombin. In patients undergoing subacute or elective percutaneous
coronary intervention, bivalirudin + provisional glycoprotein IIb/IIIa inhibition
is as effective as unfractionated heparin + glycoprotein IIb/IIIa inhibition and
is associated with a reduced risk of bleeding. The results of ongoing trials will
further define the promising role of bivalirudin in the treatment of patients
with acute coronary syndromes.
PMID- 17026894
TI - [Bleeding complications after treatment with clopidogrel and acetylsalicylic acid
after acute coronary syndrome].
AB - INTRODUCTION: The Clopidogrel in Unstable Angina to Prevent Recurrent Events
(CURE) study showed that patients with unstable angina pectoris (UAP) and non-ST
elevation myocardial infarction (NSTEMI) benefit from combined therapy with
acetylsalicylic acid (ASA) and clopidogrel. However, only patients entering
clinical randomized trials were studied. We sought to assess whether the risk of
bleeding increased after the introduction of the CURE criteria in an unselected
population of Danish patients with NSTEMI or UAP. MATERIALS AND METHODS: The CURE
criteria were implemented in the Department of Cardiology, Odense University
Hospital, in December 2001. Two consecutive one-year periods were studied: period
1, December 2000-November 2001, and period 2, December 2001-November 2002.
Patient charts were reviewed, and major bleeding complications and the primary
clinical end point (non-fatal myocardial infarction, stroke or death) was
registered. Follow-up took place one year later. RESULTS: In all, 290 patients
were included in period 1 and 189 in period 2. During period 1, there were 12
(4.1%) and during period 2, 21 (11.1%) major bleeding events (odds ratio 3.07;
95% CI 1.42-6.65; p = 0.005). Compared with the patients treated with clopidogrel
and ASA in the CURE study, we also found a three times greater risk of major
bleeding in period 2. In particular, patients over 70 years of age and patients
undergoing bypass surgery were at heightened risk. The incidence of the primary
clinical end point was higher in both period 1 and period 2 than in the CURE
study. CONCLUSION: Our study demonstrates an increased risk of major bleeding in
unselected patients receiving combination therapy with ASA and clopidogrel after
UAP or NSTEMI. Major bleeding complications most frequently occur in patients
above 70 years of age and following bypass surgery.
PMID- 17026895
TI - [Peer tutorial programme as a part of the medical curriculum].
AB - This article shows the possible effects of an integrated intensive introduction
to medical school using older students as tutors for first-year students. Our
project resulted in a significant decrease in the average time to completion of
the first five semesters of the medical bachelor' degree.
PMID- 17026897
TI - [Patterns of contact with the out-of-hours service and emergency rooms by guest
workers with immigrant and refugee background in Copenhagen municipality, 1998].
AB - INTRODUCTION: Outside normal office hours, patients in Denmark with acute
conditions are treated by the out-of-hours service connected to general practice
and in the emergency rooms of hospitals. Little is known about the contact
pattern of immigrants with these services. The purpose of this study was to
compare the contact rates for immigrants (guest workers and refugees) and non
immigrants with out-of-hours service and emergency rooms and compare the results
with the total number of contacts with general practice (out-of-hours service,
daytime contacts) and emergency rooms. MATERIALS AND METHOD: Data from 2,243,633
contacts in Copenhagen 1998 registered in the National Patient Registry and
112,733 visits to emergency units were merged with information about citizenship
and place of birth in the Central Office of Civil Registration. The contacts were
described by the average number of contacts per person at risk per year. RESULTS:
The contact rates with the out-of-hours service were significantly lower for
immigrant children than for non-immigrants, whereas the number of visits to
emergency rooms did not show any differences. For both sexes aged 19-59, the
contact rates for out-of-hours service and emergency rooms were higher for
immigrants. The total number of contacts was 31-11% lower for children and those
60+ years of age and 4-20% higher for 19- to 59-year-old immigrants. CONCLUSION:
Significant differences in the use of acute services by immigrants and non
immigrants were observed. Whether this is appropriate is questionable.
PMID- 17026896
TI - [Patterns of contact with general practice in the daytime by guest workers with
immigrant and refugee background in Copenhagen municipality, 1998].
AB - INTRODUCTION: Little is known about immigrants' contact with the Danish health
system. The aim of this study was to compare the pattern of contact with general
practitioners of guest workers, refugees and non-immigrants in Copenhagen.
MATERIALS AND METHODS: 2.04 daytime contacts (home visits, clinic consultations
and telephone consultations) by 423,202 inhabitants during the year 1998 as
recorded in the National Patient Registry were merged with information about
citizenship and place of birth in the Danish Central Office of Civil
Registration. The contacts were described by the average number of contacts per
person at risk per year. The differences between non-immigrants and immigrants
were analyzed using Poisson regression. RESULTS: Immigrants and non-immigrants
showed nearly the same sex- and age-dependent contact pattern. Immigrant children
(1-18 years) and older people (60+ years) had a lower contact rate than non
immigrants in the same age groups. The 19- to 59-year-old guest worker women and
men had 3% and 5% higher contact rates and the refugee women and men 2% and 17%
higher contact rates, respectively, than non-immigrants in the same age group.
The percentage of telephone consultations was lower for immigrants and the clinic
consultation rate higher than for non-immigrants. CONCLUSION: There are sex- and
age-specific differences between immigrants and non-immigrants. If equity is a
goal in public health care, we should know more about its actual use. More
complex research designs are needed, as well as theoretical studies, to shed
light on these issues.
PMID- 17026898
TI - [Prolonged survival after accidental immersion in cold water].
AB - In a recent boat accident, a 25-year-old yachting enthusiast fell overboard and
survived for 24 hours in 17 degrees C water. Existing survival models are
discussed in this case report. There is a discrepancy regarding survival
probability amongst the various models. The calculated survival time for the
yachtsman ranges from 3 hours to more than 30 hours. A reliable survival-time
model is needed to determine the appropriate search duration of rescue services.
In this case, the majority of the models underestimated the actual survival time.
PMID- 17026899
TI - [Tumor-induced colocolonic invagination in an adult].
AB - A case of colocolonic invagination is presented. The mass was palpated
preoperatively and diagnosed by barium enema X-ray and ultrasound. Operation
confirmed the diagnosis and demonstrated a coecum tumor. The patient was treated
successfully with a right hemicolectomy.
PMID- 17026900
TI - [Picture of the month: FLAIR].
PMID- 17026907
TI - The endovascular explosion: an interview with Dr. Edward B. Diethrich. Interview
by Roger T. Gregory.
AB - Dr. Edward B. Diethrich, a pioneer in endovascular surgery, discusses the
evolution, maturation, and future of endovascular surgery from a personal
perspective.
PMID- 17026908
TI - Total laparoscopic aortic surgery versus minimal access techniques: review of
more than 600 patients.
AB - In the following paper we describe our experience with a large number of patients
in which either a laparoscopic assisted procedure or a total laparoscopic
operation was performed. From 1996 until 2005 a total number of 638 aortic
patients were operated on using a total laparoscopic or a laparoscopic assisted
approach. A total laparoscopic operation was accomplished in 236 cases. A
laparoscopic assisted aortic operation was performed in 402 patients. In aneurysm
patients a tube graft was more frequently implanted. Thirty-day mortality was
significantly higher in patients with a total laparoscopic abdominal aortic
aneurysm repair (3.0%) compared to a laparoscopic assisted procedure (1.8%).
There was no significant difference in mortality in patients with occlusive
disease and a total laparoscopic aortofemoral bypass versus a laparoscopically
assisted operation. The same tendency could be observed when analyzing the
incidence of major perioperative complications. Again we found no significant
difference in patients with occlusive disease yet more severe complications
directly related to the operation in patients with a total laparoscopic aneurysm
repair. There was a significantly increased complication rate in total
laparoscopic aortoiliac repair with a bifurcated prosthesis compared to a tube
graft repair: a tendency we could not observe in aneurysm patients with a
laparoscopic assisted operation. Our data also show that there is a lot of room
for technical improvements such as stapling devices or special grafts to reduce
total operating times as well as the period of aortic crossclamping. The routine
use of a minilaparotomy can hardly be a solution considering the technical
drawbacks such as impaired vision and long term complications like ventral
hernias. Compared to open surgery the midterm results of laparoscopic aortic
procedures are promising. The time has come to prove that good results can be
obtained in more than a few specialized centers.
PMID- 17026909
TI - Statins and biomarkers in claudicants with peripheral arterial disease: cross
sectional study.
AB - This exploratory substudy of The Iron (Fe) and Atherosclerosis Study (FeAST)
compared baseline inflammatory markers, including cytokines, C-reactive protein
(CRP), and ferritin, in subjects with peripheral arterial disease (PAD) taking
statins with subjects with PAD who were not taking statins. Inflammatory markers
in the serum of 47 subjects with PAD not taking statins and a healthy cohort of
21 medication-free men were compared with 53 PAD subjects taking statins at entry
to the FeAST. Healthy subjects demonstrated lower levels of tumor necrosis factor
(TNF)-R1, interleukin-6 (IL-6), and CRP. TNF-alpha R1 averaged 2.28 ng/mL versus
3.52 ng/mL, p = .0025; IL-6 averaged 4.24 pg/mL versus 16.61 pg/mL, p = .0008;
and CRP averaged 0.58 mg/dL versus 0.92 mg/dL, p = .0192. A higher level of IL-6
was observed in PAD statin takers versus PAD subjects not taking statins: 19.47
pg/mL versus 13.24 pg/mL, p = .0455. As expected, total cholesterol and low
density lipoprotein levels were lower in the statin-treated group, p = .0006 and
p = .0001, respectively. No significant differences in inflammatory cytokines
were detected for varying doses of simvastatin. Additionally, no significant
differences in inflammatory biomedical markers were found in subjects with PAD
alone compared with those with concomitant coronary artery disease (CAD).
Unexpectedly, serum inflammatory cytokine IL-6 levels were significantly higher
in PAD subjects receiving statins. There was no difference in measured
inflammatory markers in PAD subjects with concomitant CAD.
PMID- 17026910
TI - Importance of the arteriographic anatomy of the descending genicular artery and
sural arteries in patients with atherosclerotic occlusion of the popliteal
artery.
AB - Bypasses to the descending genicular artery (DGA) or the medial sural artery
(MSA) have been performed with acceptable rates of midterm success. The
arteriographic appearance of the DGA, the MSA, and the lateral sural artery (LSA)
was described and the applicability of bypass to these vessels was investigated.
The arteriograms of 45 patients who had occlusion of the below-knee popliteal
artery were analyzed to determine the presence, dominance, and extension of
collaterals for each perigeniculate branch, which were used to assess the
applicability of a perigeniculate bypass. A dominant perigeniculate artery was
found in 26 arteriograms and corresponded to 13 DGAs, 9 MSAs, and 4 LSAs. Of 14
applicable perigeniculate bypasses, 2 would be an obligatory bypass and 12 would
be an alternative to a conventional infrapopliteal bypass. Although rarely an
obligatory solution, a bypass to a perigeniculate branch artery represents a
valuable alternative.
PMID- 17026911
TI - Long-term outcome of operated inflammatory aortic aneurysms.
AB - Inflammatory aortic aneurysms (IAAs) represent a rare form of aortic aneurysms.
Compared with atherosclerotic aneurysms, patients with IAA have an increased risk
of perioperative and long-term morbidity. This retrospective clinical study
analyzed the outcome after conventional and endovascular repair of IAAs. Patients
treated for an abdominal IAA between January 1995 and November 2004 were
included. Imaging (computed tomographic angiography or magnetic resonance
angiography) was performed preoperatively and at the time of follow-up (mean 2.7
years). Transperitoneal open repair and endovascular aortic repair were the
operative procedures used. Over 10 years, 40 patients were treated with
conventional and 5 patients with endovascular repair. The in-hospital morbidity
rate was 11.1% (five patients; four conventional, one endovascular). On 10
patients (47.6%), the retroperitoneal fibrosis was no longer detectable. After
operative repair, the majority of cases presented with a distinct regression of
inflammation. Endovascular treatment of IAA represents a feasible alternative
procedure to open aortic repair.
PMID- 17026912
TI - Endovascular repair for thoracic aortic disease: tertiary single-center
experience in northwestern Greece.
AB - The purpose of this article is to report the initial experience with endovascular
repair of thoracic aortic disease in a single tertiary vascular unit in
northwestern Greece. Between 2003 and 2005, 16 patients were treated with
endovascular techniques for various pathologies of the descending thoracic aorta.
Twelve patients were treated electively and four emergently. Operative and follow
up data for a mean time of 18.4 months were retrospectively collected and
analyzed. Primary technical success was obtained in 14 (87.5%) cases. No early or
late deaths occurred, and there was no major operation-related complication. No
paraplegia was observed in our patients. Stent graft-related complications
occurred in 18.75% (one type 2 and two type 3 endoleaks), but they all had a
favorable outcome. No further problems have been reported in any of our patients.
Endovascular stent graft repair for diseases of the thoracic aorta seems to be a
promising alternative to open surgery, especially for high-risk patients. Long
term results are needed to confirm the early benefit of this treatment option
with regard to morbidity and mortality rates. The potential of this technique to
be applicable even in relatively small, tertiary vascular centers might be of
great benefit to patients.
PMID- 17026913
TI - Novel access technique facilitating carotid artery stenting.
AB - Carotid artery stenting (CAS) may be impossible, or associated with a high risk,
in patients with severe vessel tortuosity. A novel method of catheterization of
the carotid artery intended to facilitate CAS is described. It involves the
placement of a microcatheter and a coronary wire through a dissected superficial
temporal artery (STA), and then advanced to the ascending aorta. The wire is then
snared and brought out through a sheath already placed from the common femoral
artery (CFA). Thus through-and-through access from the STA to the CFA is
established. The sheath is then brought over the coronary artery into the common
carotid artery. Using the coronary artery as "buddy wire" the carotid artery
stenting is carried out in a standard fashion. The potential benefit of this new
technique is the decrease of risk of the procedures in patients with prohibiting
vessel tortuosity.
PMID- 17026914
TI - Endovascular management of blunt abdominal aortic injury.
AB - The endovascular management of blunt aortic injuries is being used more
frequently in the trauma patient. Traumatic aortic injuries usually occur in the
descending thoracic aorta near the origin of the left subclavian artery. Many
reports in the literature demonstrate the efficacy of endovascular repair of
blunt thoracic aortic injury. We report here an unusual case of abdominal aortic
dissection secondary to blunt abdominal trauma following a fall. The patient also
had associated intra-abdominal injuries requiring bowel resection and repair of
small bowel mesenteric lacerations. He was treated with a bifurcated abdominal
endograft with an excellent result after the initial operation was performed to
treat the bowel injuries.
PMID- 17026915
TI - Rupture of a popliteal artery aneurysm 10 years after surgical repair.
AB - The usual method for popliteal artery aneurysm exclusion is distal and proximal
ligation followed by bypass grafting via a medial approach. This technique
preserves collaterals to the aneurysm, which might cause back-bleeding and
symptomatic enlargement. We report the eighth case in the literature of a
ruptured popliteal artery aneurysm after previous ligation and bypass grafting.
The ruptured aneurysm was successfully excluded via a posterior approach. The
advantage of this approach over the medial approach is the possibility of opening
the aneurysm sac to oversew patent side branches, thereby excluding back
bleeding. We review the advantages and disadvantages of both the medial and the
dorsal technique to treat popliteal aneurysms.
PMID- 17026916
TI - Endovascular exclusion of subclavian artery pseudoaneurysm.
AB - Subclavian artery pseudoaneurysms are typically a rare occurrence commonly caused
by iatrogenic injury and trauma. We describe an endovascular approach employing a
brachiofemoral through-wire technique for the treatment of a left subclavian
artery pseudoaneurysm in the presence of a hostile aortic arch and great vessel
anatomy.
PMID- 17026917
TI - [Photonic revolution or how non linear optics fosters new approaches in cell and
tissue imaging].
PMID- 17026918
TI - [Human embryonic stem cells to rescue fulminant hepatic failure].
PMID- 17026920
TI - [New hopes for cancer immunotherapy].
PMID- 17026919
TI - [Salmonella transcriptome during macrophage infection].
PMID- 17026921
TI - [The UN peace-keeping force in the plants: A microRNA, miR164, stabilizes the
boundary domain in the meristem].
PMID- 17026922
TI - [Uncoupling between noradrenergic and serotonergic neurons: As a mechanism for
drug addiction].
PMID- 17026923
TI - [Functional dissection of a new regulator of DNA replication initiation in
bacteria].
PMID- 17026924
TI - [Help yourself and the sky will help you! On the importance of radiative heat
exchange during nocturnal flight in birds].
PMID- 17026925
TI - [NEDD1 and microtubule nucleation complexes: To recruit for better organizing].
PMID- 17026926
TI - [The dog and its genome].
PMID- 17026927
TI - [A neuropeptide at the origin of testicular aging?].
PMID- 17026928
TI - [Two sensors to control bacterial life style: the choice between chronic or acute
infection].
PMID- 17026929
TI - [Modeling as a tool for analysis in developmental biology].
PMID- 17026930
TI - [Diversity of plant-pollinator interaction and stability of ecosystems].
PMID- 17026931
TI - [New approach of fibrosis by multiphoton microscopy with second harmonic
generation].
PMID- 17026932
TI - [Bone marrow stem cells to the rescue of Alzheimer's disease].
PMID- 17026933
TI - [Unexpected properties of red blood cell anion exchanger: The fish lesson].
PMID- 17026934
TI - [Connexins, renin and hypertension].
PMID- 17026935
TI - [Nanog and the magic wand].
PMID- 17026937
TI - [Two-photon laser scanning fluorescence microscopy for functional cellular
imaging: Advantages and challenges or One photon is good... but two is better!].
AB - One of the main challenges of modern biochemistry and cell biology is to be able
to observe molecular dynamics in their functional context, i.e. in live cells in
situ. Thus, being able to track ongoing molecular events with maximal spatial and
temporal resolution (within subcellular compartments), while minimizing
interference with tissue biology, is key to future developments for in situ
imaging. The recent use of non-linear optics approaches in tissue microscopy,
made possible in large part by the availability of femtosecond pulse lasers, has
allowed major advances on this front that would not have been possible with
conventional linear microscopy techniques. Of these approaches, the one that has
generated most advances to date is two-photon laser scanning fluorescence
microscopy. While this approach does not really provide improved resolution over
linear microscopy in non absorbing media, it allows us to exploit a window of low
absorbance in live tissue in the near infrared range. The end result is much
improved tissue penetration, minimizing unwanted excitation outside the focal
area, which yields an effective improvement in resolution and sensitivity. The
optical system is also simplified and, more importantly, phototoxicity is
reduced. These advantages are at the source of the success of two-photon
microscopy for functional cellular imaging in situ. Yet, we still face further
challenges, reaching the limits of resolution that conventional optics can offer.
Here we review some recent advances in optics/photonics approaches that hold
promises to improve our ability to probe the tissue in finer areas, at faster
speed, and deeper into the tissue. These include super-resolution techniques,
introduction of non paraxial optics in microscopy and use of amplified
femtosecond lasers, yielding enhanced spatial and temporal resolution as well as
tissue penetration.
PMID- 17026938
TI - [Second- and third-harmonic generation microscopies for the structural imaging of
intact tissues].
AB - One principal advantage of multiphoton excitation microscopy is that it preserves
its three-dimensional micrometer resolution when imaging inside light-scattering
samples. For that reason two-photon-excited fluorescence microscopy has become an
invaluable tool for cellular imaging in intact tissue, with applications in many
fields of physiology. This success has driven increasing interest in other forms
of nonlinear microscopy that can provide additional information on cells and
tissues, such as second- (SHG) and third- (THG) harmonic generation microscopies.
In recent years, significant progress has been made in understanding the contrast
mechanisms of these recent methodologies, and high-resolution imaging based on
intrinsic sources of signal has been demonstrated in cells and tissues. Harmonic
generation exhibits structural rather than chemical specificity and can be
obtained from a variety of non-fluorescent samples. SHG is observed specifically
in dense, non-centrosymmetric arrangements of polarizable molecules, such as
collagen fibrils, myofilaments, and polarized microtubule bundles. SHG imaging is
therefore emerging as a novel approach for studying processes such as the
physiopathological remodelling of the collagen matrix and myofibrillogenesis in
intact tissue. THG does not require a non-centrosymmetric system ; however no
signal can be obtained from a homogeneous medium. THG imaging therefore provides
maps of sub-micrometer heterogeneities (interfaces, inclusions) in unstained
samples, and can be used as a general purpose structural imaging tool. Recent
studies showed that this technique can be used to image embryo development in
small organisms and to characterize the accumulation of large lipid bodies in
specialized cells. SHG and THG microscopy both rely on femtosecond laser
technology and are easily combined with two-photon microscopy.
PMID- 17026939
TI - [Stimulated Raman microscopy (CARS): From principles to applications].
AB - A new technique in microscopy is now available which permits to image specific
molecular bonds of chemical species present in cells and tissues. The so called
Coherent Anti-Stokes Raman Scattering (CARS) approach aims at maximizing the
light matter interaction between two laser pulses and an intrinsic molecular
vibrational level. This is possible through a non linear process which gives rise
to a coherent radiation that is greatly enhanced when the frequency difference
between the two laser pulses equals the Raman frequency of the aimed molecular
bond. Similar to confocal microscopy, the technique permits to build an image of
a molecular density within the sample but doesn't require any labelling or
staining since the contrast uses the intrinsic vibrational levels present in the
sample. Images of lipids in membranes and tissues have been reported together
with their spectral analysis. In the case of very congested media, it is also
possible to use a non invasive labelling such as deuterium which shifts the
molecular vibration of the C-H bond down to the C-D bond range which falls in a
silent region of the cell and tissue vibrational spectra. Such an approach has
been used to study lipid phase in artificial membranes. Although the technique is
still under development, CARS has now reach a maturity which will permit to bring
the technology at a commercial stage in the near future. The last remaining
bottleneck is the laser system which needs to be simplified but solutions are now
under evaluation. When combined with others more conventional techniques, CARS
should give its full potential in imaging unstained samples and like two photons
techniques has the potential of performing deep tissues imaging.
PMID- 17026940
TI - [Full-field OCT].
AB - Optical coherence tomography (OCT) is an emerging technique for imaging of
biological media with micrometer-scale resolution, whose most significant impact
concerns ophthalmology. Since its introduction in the early 1990's, OCT has known
a lot of improvements and sophistications. Full-field OCT is our original
approach of OCT, based on white-light interference microscopy. Tomographic images
are obtained by combination of interferometric images recorded in parallel by a
detector array such as a CCD camera. Whereas conventional OCT produces B-mode
(axially-oriented) images like ultrasound imaging, full-field OCT acquires
tomographic images in the en face (transverse) orientation. Full-field OCT is an
alternative method to conventional OCT to provide ultrahigh resolution images
(approximately 1 microm), using a simple halogen lamp instead of a complex laser
based source. Various studies have been carried, demonstrating the performances
of this technology for three-dimensional imaging of ex vivo specimens. Full-field
OCT can be used for non-invasive histological studies without sample preparation.
In vivo imaging is still difficult because of the object motions. A lot of
efforts are currently devoted to overcome this limitation. Ultra-fast full-field
OCT was recently demonstrated with unprecedented image acquisition speed, but the
detection sensitivity has still to be improved. Other research directions include
the increase of the imaging penetration depth in highly scattering biological
tissues such as skin, and the exploitation of new contrasts such as optical
birefringence to provide additional information on the tissue morphology and
composition.
PMID- 17026941
TI - [Regulation of p16INK4a, senescence and oncogenesis].
AB - The transcriptional regulation of p16INK4a is essential for cellular aging and
oncogenic stress response. This regulation involves p16INK4a transcriptional
activators such as proteins Ets1 and 2 or E47. The binding of these proteins to
INK4a promoter can be inhibited by proteins Id-1 or -4 after heterodimer
formation. The transcriptional inhibition of p16INK4a includes also the
transcriptional repression by Bmi-1, and an epigenetic regulation which appears
complex and remains incompletely understood. Actually, INK4a promoter and exon1
present a CpG island which can be methylated on cytosines by DNA
methyltransferases. This DNA methylation is preceded by the lysine 9 histone H3
methylation and by the deacetylation of histone H4 both involved in gene
silencing. Indeed, RNA Helicase A might protect INK4a against methylation of CpG
island. Furthermore, chromatin remodelling involving SWI/SNF complex, antagonist
to Bmi-1, might activate INK4a expression. The analysis of INK4a regulation
mechanisms and the comprehension of the epigenetic modulation of its expression
may allow us to develop a rational use of new anti-neoplastic agents.
PMID- 17026942
TI - [PI3-kinase: Linking immunological synapse to T-cell proliferation].
AB - T cell clonal expansion contributing to host defense against pathogens is a
tightly controlled process to maintain the homeostasis of the immune system. Our
understanding of how T cell growth and proliferation are controlled following
antigenic stimulation is therefore a major challenge. Antigen recognition occurs
when a naive T lymphocyte contacts an antigen-presenting cell. A specialized
junction enriched in T-cell receptors, costimulation molecules and signaling
adaptors, called the immunological synapse, is then created for several hours
between the two cell types. Recent discoveries now clarify the molecular
mechanisms used by this organization to control T cell growth and proliferation.
It has been established that the immunological synapse functions in fact as an
integrative platform where class Ia phosphoinositide-3-kinases (PI3Ks) are
recruited and activated to continuously produce high levels of 3'
phosphoinositides. These lipids regulate the localization and the activation of a
wide range of PH-domain containing proteins, among which the serine-threonine
kinase Akt, a downstream effector of PI3Ks, appears to be a key player. FoxO
(Forkhead subgroup O) family members control in various cell systems genes
implicated in apoptosis, stress resistance and cell cycle arrest, thereby
contributing to maintain quiescence in unstimulated cells. In naive T cells
contacting antigen-presenting cells a rapid but also very prolonged nuclear
exclusion of these transcription factors is observed downstream of Akt. Mainly,
this compartmentalization process is mandatory to induce T cell growth triggered
by the T cell/antigen-presenting cell interaction. These findings demonstrate
that to initiate cell cycle progression the formation of the immunological
synapse is an undemanding tactic used by primary T cells to securely maintain the
3'-phosphoinositide-dependent mitotic switch governed by the spatial control of
FoxO transcription factors.
PMID- 17026943
TI - [Tuberculosis and HIV: The drama of Africa].
PMID- 17026944
TI - [Differences and similarities of industrial and institutional promotions].
AB - The Delegation a la Recherche Clinique d'Ile-de-France et de l'Assistance
Publique/Hopitaux de Paris (AP-HP) has elaborated a pragmatic approach for the
monitoring of institutionally sponsored clinical studies. The mandatory practices
aiming at preventing enrolled volunteers from risks and results from fraud and
poor quality have been reviewed and a four-stage graduate monitoring has been
defined, which is applied since 2002. This system needs to be scientifically
assessed and adapted to the permanent evolution of national and international
regulations. double dagger.
PMID- 17026945
TI - [Targets of antithrombotic drugs].
AB - New antithrombotic agents are being developed not only to improve efficacy, but
also to increase safety in comparison with widely used conventional agents such
as the oral anticoagulants. New anticoagulant, antiplatelet, and profibrinolytic
compounds are currently under study in drug development programs, and most of
those in phase II or III of development are derived from the observation of
natural phenomena and merely mimic processes developed by mammalians, including
humans, to avoid thrombosis, or by blood-sucking insects or animals to prevent
coagulation of the blood their are feeding on. By contrast, drug candidates
identified by means of rigorous research and designed to target new pathways and
achieve direct and specific inhibition of factors that are presumed to play an
important role in thrombogenesis have generally failed to show any benefit and
sometimes even induce deleterious effects. The clinical development of new drugs,
even those mimicking natural phenomena, improves our knowledge of the
pathogenesis of thrombosis and sheds light, retrospectively, on previous
conceptual errors. The improvement in our basic knowledge and the development of
new types of drugs suggest that, in contrast to the current antithrombotic
compounds that are used in a broad range of clinical settings, use of new drugs
should be restricted to specific situations in which their mechanisms of action
are predicted to deliver the highest medical benefit. A major obstacle resides in
the fact that current drug development programs are still required to comply with
long obsolete guidelines based on the characteristics of first-generation
antithrombotic agents, and that do not take into account the specific mechanisms
of action of new drugs. This situation should change, however, and new
antithrombotic drugs should soon be able to benefit from adapted development
programs that will make it possible to determine their optimal risk-benefit
ratio.
PMID- 17026946
TI - Issues in using state hospital discharge data in injury control research and
surveillance.
AB - This study evaluates the quality of injury-related coding in state hospital data
and their usefulness to injury researchers. Using 1997 hospital discharge records
from 19 states, hospitalized non-fatal injury-related cases were identified by
first selecting all cases that met broad criteria for injury, and then dropping
cases that appeared incorrectly coded as injuries and cases related to medical
care. Based on our criteria, 1,129,980 non-fatal hospitalized cases were
identified as probable acute injuries. Three-quarters were coded with a
traditional injury diagnosis in the primary diagnosis field, and 90% had a
traditional injury diagnosis somewhere in the first six diagnosis fields. Of
cases with an injury diagnosis code in the first three diagnosis fields, 88.1%
were E coded. E coding completeness varied by state, with some states reporting
high rates of E coding by using non-specific E codes. Other challenges included E
coded cases where no injury diagnosis was reported and apparent miscoding of the
E code. We conclude that it is possible to combine multiple states' data if
researchers are aware of the challenges they may encounter. In order to capture
all injury-related cases, it is important to scan secondary diagnosis fields.
PMID- 17026947
TI - Health status of lymphatic filariasis assessed from patients using seven domains
five levels (7D5L) instrument.
AB - Health status is the standardized description of health condition of individuals
either normal or ill due to diseases and is presented as multidimentional
profiles. In an effort to develop an indicator to assess the impact of morbidity
intervention against lymphatic filariasis (LF), we assessed the health status of
seven different clinical manifestations (health states) of LF from the patient's
perspective. One hundred and seventy-four filarial patients either with hydrocele
or lymphoedema were involved in the study. Acute episode of adenolymphangitis
(ADL) among chronic patients was considered as co-morbidity. Severity levels,
focusing on physical, mental and social dimensions of health were defined and
quantified, using seven domains and five levels (7D5L) instrument, an extended
form of EuroQol (5D3L). All the seven domains of health are affected by filarial
disease, with the levels of severity varying with health states. The mean
severity score of ADL (25.8) was significantly higher compared to lymphoedema
(10.7) and hydrocele (6.9) (P<0.05). In males, the mean score of lymphoedema
(11.6) was significantly higher in comparison to hydrocele (P<0.05). The severity
scores increase with the progression of filarial disease but independent of
gender. The health states of LF were further classified based on the percentage
of severity according to International Classification of Functioning, Disability
and Health (ICF) on impairments. Lymphoedema grade 4 (oedema with skin changes)
and ADL were ranked as severe. The importance of these findings is discussed in
view of priority setting and evaluating the morbidity management under Global
Programme for Elimination of Lymphatic Filariasis (GPELF).
PMID- 17026948
TI - Birth weight and neurodevelopmental outcome of children at 2 years of age after
planned vaginal delivery for breech presentation at term.
PMID- 17026950
TI - Myth of the ideal cesarean section rate: commentary and historic perspective.
PMID- 17026951
TI - Histological and biomechanical evaluation of implanted graft materials in a
rabbit vaginal and abdominal model.
AB - OBJECTIVE: The objective of the study was to describe the histologic and
biomechanical changes of implanted dermal collagen graft materials. STUDY DESIGN:
Twenty rabbits were randomized into 2 groups (6 and 12 weeks, respectively). Each
rabbit had 4 graft segments (human dermis, porcine dermis, porcine collagen
coated polypropylene mesh, and autologous fascia) randomly implanted into the
abdomen and the vagina. Biomechanical testing and histologic analysis was
performed after recovery of graft segments. RESULTS: Dermal graft segments showed
a marked decrease in ultimate strength (84% to 86%) and elastic modulus (73% to
82%) that was significantly different from the decrease seen in autologous fascia
or coated synthetic mesh (P < .0008 and P < .0001, respectively). The decrease in
ultimate strength was associated with vaginal implantation (P = .057). Dermal
graft materials had moderate inflammation and minimal collagen infiltration.
CONCLUSION: The mechanical properties of dermal graft materials decline after
implantation. Vaginal implantation may cause a different tissue response to graft
material than abdominal implantation. Dermal graft material caused moderate
inflammation and minimal collagen ingrowth remote from implantation.
PMID- 17026953
TI - Serotonin transporter, tryptophan hydroxylase, and monoamine oxidase A gene
polymorphisms in premenstrual dysphoric disorder.
AB - OBJECTIVE: The purpose of this study was to investigate whether common
polymorphisms of key genes that control the serotonin (5-hydroxytryptamine)
pathway are associated with premenstrual dysphoric disorder. STUDY DESIGN: The
study sample comprised 53 women with clinically diagnosed premenstrual dysphoric
disorder (age range, 27-46 years; mean age, 37.7 years) and 52 healthy control
subjects (age range, 22-48 years; mean age, 36.2 years). Eight polymorphisms that
encode the 5-hydroxytryptamine transporter (LPR, VNTR-2, and 3' UTR G/T),
tryptophan hydroxylase 1 (TPH1 G-6526A, G-5806T, and A218C), and monoamine
oxidase A (monoamine oxidase A promoter VNTR-1 and exon 8 Fnu 4H1) were
genotyped. Genotype and allelic frequencies were analyzed by chi-square test and
stepwise logistic regression analysis. RESULTS: There was no significant
association between any genotype and clinical category and no significant allelic
distribution profiles in either the premenstrual dysphoric disorder group or the
control group. CONCLUSION: These findings do not support a major role for common
5-hydroxytryptamine transporter, TPH1, and monoamine oxidase A polymorphisms in
contributing to susceptibility to premenstrual dysphoric disorder.
PMID- 17026954
TI - [Results of pancreatic cancer surgery].
PMID- 17026956
TI - Telomerase with mutated catalytic motifs has dominant negative effects on
telomerase activity and inhibits cell growth.
AB - Telomerase catalytic subunit (TERT) seems a key factor controlling telomerase
activity, telomere length, and cell growth. To further address this issue, we
forced expression of a catalytically inactive mutant human TERT (hTERT) in hTERT
immortalised sheep fibroblasts to examine its effects. Expression of mutant hTERT
compromised telomerase activity reconstituted by wild-type hTERT in a manner
directly attributable to mutant hTERT expression level. High levels of mutant
hTERT expression inhibited cell growth with a subset of cells entering
replicative senescence. Furthermore, significant telomere attrition was evident
in two of three clones with high levels of mutant hTERT expression. Our findings
are consistent with the notion that hTERT homodimers are necessarily required to
form a functional telomerase complex at the telomere substrate. We also highlight
the requirement of a more thorough understanding of telomerase- and telomere
associated factors to understand fully the interplay that governs telomere
homeostasis in vitro and in vivo.
PMID- 17026955
TI - Self-association of isolated large cytoplasmic domain of plasma membrane H+
ATPase from Saccharomyces cerevisiae: role of the phosphorylation domain in a
general dimeric model for P-ATPases.
AB - Large cytoplasmic domain (LCD) plasma membrane H+ -ATPase from S. cerevisiae was
expressed as two fusion polypeptides in E. coli: a DNA sequence coding for Leu353
Ileu674 (LCDh), comprising both nucleotide (N) and phosphorylation (P) domains,
and a DNA sequence coding for Leu353-Thr543 (LCDDeltah, lacking the C-terminus of
P domain), were inserted in expression vectors pDEST-17, yielding the respective
recombinant plasmids. Overexpressed fusion polypeptides were solubilized with 6 M
urea and purified on affinity columns, and urea was removed by dialysis. Their
predicted secondary structure contents were confirmed by CD spectra. In addition,
both recombinant polypeptides exhibited high-affinity 2',3'-O-(2,4,6
trinitrophenyl)adenosine-5'-triphosphate (TNP-ATP) binding (Kd = 1.9 microM and
2.9 microM for LCDh and LCDDeltah, respectively), suggesting that they have
native-like folding. The gel filtration profile (HPLC) of purified LCDh showed
two main peaks, with molecular weights of 95 kDa and 39 kDa, compatible with
dimeric and monomeric forms, respectively. However, a single elution peak was
observed for purified LCDDeltah, with an estimated molecular weight of 29 kDa, as
expected for a monomer. Together, these data suggest that LCDh exist in monomer
dimer equilibrium, and that the C-terminus of P domain is necessary for self
association. We propose that such association is due to interaction between
vicinal P domains, which may be of functional relevance for H+ -ATPase in native
membranes. We discuss a general dimeric model for P-ATPases with interacting P
domains, based on published crystallography and cryo-electron microscopy
evidence.
PMID- 17026957
TI - Analysis of the XBP1 splicing mechanism using endoplasmic reticulum stress
indicators.
AB - Under endoplasmic reticulum (ER) stress conditions, XBP1 mRNA is processed by
unconventional splicing and translated into a functional transcription factor. ER
stress-specific XBP1 splicing is also known to be activated by IRE1. However,
many aspects of the molecular mechanism of XBP1 splicing remain to be elucidated.
We previously developed an indicator system that enabled detection of XBP1
splicing using fluorescent proteins as the reporter signals. Here, we use a
modification of this method that employs modified ER stress-indicators and mutant
IRE1 in vivo and in vitro to analyze XBP1 splicing mechanisms. Our analyses
suggest that the 506-579 nt region of the XBP1 mRNA is necessary and sufficient
for XBP1 splicing, that XBP1 splicing can occur in the cytoplasm, and that
cleavage and ligation of XBP1 mRNA during splicing may occur as a coupled
reaction.
PMID- 17026958
TI - p38MAPK mediates benzyl isothiocyanate-induced p21WAF1 expression in vascular
smooth muscle cells via the regulation of Sp1.
AB - It has recently been reported that the transcription factors involved in p21WAF1
activation by certain signaling factors may vary in different cell types.
However, the role and importance of the signaling pathway in the transcriptional
regulation of p21WAF1 on vascular smooth muscle cells (VSMC) in response to
benzyl isothiocyanate (BITC) has been unclear. In this report, we demonstrate
that BITC induces the p21WAF1 expression at the transcriptional level. This
increase in p21WAF1 gene expression was due to p38MAPK-dependent activation of
the p21WAF1 promoter by BITC. Transcription factor Sp1 binding site was
identified as the cis-element for the activation of p21WAF1 promoter by BITC, as
determined by deletion and mutation analysis. In addition, gel shift and
supershift assays demonstrated that this BITC-responsive element binds
specifically to the transcription factor Sp1. Treatment with SB203580, an
inhibitor of the p38MAPK, significantly downregulated transactivation of BITC
induced Sp1. Finally, the transient expression of VSMC with dominant negative
p38MAPK plasmid suppressed BITC-stimulated Sp1 activity. In conclusion, we report
that the transcription factor Sp1 involved in the p38MAPK-mediated control of
p21WAF1 regulation on VSMC in response to BITC has now been identified.
PMID- 17026959
TI - Association and insulin regulated translocation of hormone-sensitive lipase with
PTRF.
AB - Polymerase I and transcript release factor (PTRF) is in human adipocytes mainly
localized at the plasma membrane. This localization was under control of insulin,
which translocated PTRF to the cytosol and nucleus, indicating a novel role for
PTRF in insulin transcriptional control. In the plasma membrane PTRF was
specifically bound to a triacylglycerol-metabolizing subclass of caveolae
containing hormone-sensitive lipase (HSL). In response to insulin PTRF was
translocated to the cytosol in parallel with HSL. PTRF and HSL were
quantitatively immunoprecipitated from the cytosol by antibodies against either
PTRF or HSL. The findings indicate also a novel extranuclear function for PTRF in
the control of lipolysis.
PMID- 17026960
TI - Dickkopf-1 induced apoptosis in human placental choriocarcinoma is independent of
canonical Wnt signaling.
AB - Placental choriocarcinoma, a reproductive system carcinoma in women, has about
0.81% occurrence frequency in China, which leads to over 90% lethality due to
indistinct pathogenesis and the absence of efficient therapeutic treatment. In
the present study, using immunostaining and reverse transcription PCR, we
reported that Dickkopf-1 (Dkk-1) is prominently expressed in human
cytotrophoblast (CTB) cell, but absent in the human placental choriocarcinoma
cell line JAR and JEG3, implicating an unknown correlation between Dkk-1 and
carcinogenesis of placental choriocarcinoma. Further, through exogenous
introduction of Dkk-1, we found repressed proliferation in JAR and JEG3, induced
apoptosis in JAR, and discovered significant tumor suppression effects of Dkk-1
in placental choriocarcinoma. Moreover we found that this function of Dkk-1 is
achieved through c-Jun N-terminal kinase (JNK), whereas the canonical Wnt pathway
may not have a great role. This discovery is not symphonic to previous functional
understanding of Dkk-1, a canonical Wnt signaling antagonist. Together, our data
indicate the possible correlation between Dkk-1 and human placental
choriocarcinoma and suggest potential applications of Dkk-1 in treatment of human
placental choriocarcinomas.
PMID- 17026961
TI - Hypo-osmotic shock induces nuclear export and proteasome-dependent decrease of
UBL5.
AB - The osmolarity of body fluid is strictly controlled through the action of
diuretic hormones, which are secreted in the hypothalamus. In the mammalian
brain, ubiquitin-like 5 (UBL5) is expressed in oxytocin- and vasopressin-positive
neurons in the hypothalamus, and these neurons play a role in regulating
osmolarity. We examined the dynamics of UBL5 levels in response to hyper- or hypo
osmotic conditions. Hypo-osmotic conditions led to significantly reduced levels
of UBL5 both in brain slices from the hypothalamus and in NIH-3T3 cells. This
decrease in UBL5 was transcription-independent and proteasome-dependent. Time
course immunocytochemical studies using exogenous UBL5 revealed that the protein
was exported from the nucleus under hypo-osmotic conditions and decreased in a
proteasome-dependent manner. This report is the first to describe changes in the
intracellular and subcellular localization of UBL5 in response to hypo-osmotic
conditions. Our results imply osmoregulation of UBL5.
PMID- 17026962
TI - Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal
cord.
AB - Expressions of the growth hormone secretagogue receptor (GHS-R) mRNA and its
protein were confirmed in rat fetal spinal cord tissues by RT-PCR and
immunohistochemistry. In vitro, over 3 nM ghrelin and des-acyl ghrelin induced
significant proliferation of primary cultured cells from the fetal spinal cord.
The proliferating cells were then double-stained using antibodies against the
neuronal precursor marker, nestin, and the cell proliferation marker, 5-bromo-2'
deoxyuridine (BrdU), and the nestin-positive cells were also found to be co
stained with antibody against GHS-R. Furthermore, binding studies using [125I]des
acyl ghrelin indicated the presence of a specific binding site for des-acyl
ghrelin, and confirmed that the binding was displaced with unlabeled des-acyl
ghrelin or ghrelin. These results indicate that ghrelin and des-acyl ghrelin
induce proliferation of neuronal precursor cells that is both dependent and
independent of GHS-R, suggesting that both ghrelin and des-acyl ghrelin are
involved in neurogenesis of the fetal spinal cord.
PMID- 17026963
TI - Ethanol augments elevated-[Ca2+]C induced trypsin activation in pancreatic acinar
zymogen granules.
AB - It has been long recognized that significant percentage of patients with acute
pancreatitis often presents with a history of excessive alcohol consumption;
however, the patho-physiological effect of ethanol on acute pancreatitis remains
poorly understood. Abnormally elevated cytosolic Ca2+ ([Ca2+]C) has been found to
be a shared phenomenon in acute pancreatitis that could induce trypsin premature
activation. Here, we present the effects of ethanol to sensitize zymogen granules
(ZGs) of pancreas acinar cells to elevated [Ca2+]C leading to zymogen premature
activation that could result in acute pancreatitis. The pH fluctuations ([pH]G),
Ca2+ concentration ([Ca2+]G), and premature trypsin activation inside the ZGs
were monitored directly with specific fluorescence indicators. Our results showed
that ethanol could act directly on ZGs and cause ZGs more receptive to elevated
[Ca2+]C that could induce premature activation of zymogen (trypsin). This alcohol
induced effect is concentration dependent and strongly influenced by the
surrounding [Ca2+]C. The K+ channels on ZGs membranes are required in the
sensitization process. Our observations provide a mechanistic understanding of
the role of ethanol in the initiation phase of alcoholic pancreatitis.
PMID- 17026964
TI - Mitotic phosphorylation of tankyrase, a PARP that promotes spindle assembly, by
GSK3.
AB - The assembly and function of mitotic spindles require poly(ADP-ribosyl)ation of
spindle components by tankyrase, a poly(ADP-ribose) polymerase that aggregates to
spindle poles during mitosis. Tankyrase itself is phosphorylated during mitosis,
but the kinases involved remain undefined. Herein we report that mitotic
phosphorylation of tankyrase is abrogated in cells treated with the GSK3
inhibitors LiCl and indirubin. Moreover, the electrophoretic mobility-shift of
tankyrase arising from mitotic phosphorylation can be reproduced in vitro by GSK3
mediated phosphorylation. Lastly, mutagenesis study suggested that GSK3 in vitro
phosphorylates tankyrase on S978, T982, S987, and S991, residues that comprise
two adjacent copies of the canonical GSK3 phospho-acceptor motif [S/T]-X-X-X
[S/T]. Collectively, our data suggest that GSK3 contributes to mitotic tankyrase
phosphorylation, raising the possibility that this phosphorylation might mediate
some of the established roles of GSK3 in spindle assembly and mitotic
progression.
PMID- 17026965
TI - Single-stranded oligonucleotide-mediated gene repair in mammalian cells has a
mechanism distinct from homologous recombination repair.
AB - Single-stranded DNA oligonucleotide (SSO)-mediated gene repair has great
potentials for gene therapy and functional genomic studies. However, its
underlying mechanism remains unclear. Previous studies from other groups have
suggested that DNA damage response via the ATM/ATR pathway may be involved in
this process. In this study, we measured the effect of two ATM/ATR inhibitors
caffeine and pentoxifylline on the correction efficiency in SSO-mediated gene
repair. We also checked their effect on double-stranded break (DSB)-induced
homologous recombination repair (HRR) as a control, which is well known to be
dependent on the ATM/ATR pathway. We found these inhibitors could completely
inhibit DSB-induced HRR, but could only partially inhibit SSO-mediated process,
indicating SSO-mediated gene repair is not dependent on the ATM/ATR pathway.
Furthermore, we found that thymidine treatment promotes SSO-mediated gene repair,
but inhibits DSB-induced HRR. Collectively, our results demonstrate that SSO
mediated and DSB-induced gene repairs have distinct mechanisms.
PMID- 17026966
TI - Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse.
AB - Increased oxidative damage is a prominent and early feature in Alzheimer disease
(AD). However, whether it is a primary cause or merely a downstream consequence
in AD pathology is still unknown. We previously generated alpha-tocopherol
transfer protein knockout (Ttpa-/-) mice, in which lipid peroxidation in the
brain was significantly increased by complete depletion of alpha-tocopherol
(alpha-Toc). Here we crossed AD transgenic (APPsw) model mice (Tg2576) with Ttpa
/- mice. The resulting double-mutant (Ttpa-/- APPsw) mice showed earlier and more
severe cognitive dysfunction in the Morris water maze, novel-object recognition,
and contextual fear conditioning tests. They also showed increased amyloid beta
peptide (Abeta) deposits in the brain by immunohistochemical analysis, which was
ameliorated with alpha-Toc supplementation. In this report we provide clear
evidence indicating that chronic lipid peroxidation due to alpha-Toc depletion
enhances AD phenotype in a mouse model.
PMID- 17026967
TI - Pharmacological profiling of disulfiram using human tumor cell lines and human
tumor cells from patients.
AB - The thiocarbamate drug disulfiram has been used for decades in the treatment of
alcohol abuse. Disulfiram induces apoptosis in a number of tumor cell lines and
was recently by us proposed to act as a 26S proteasome inhibitor. In this work we
characterized disulfiram in vitro with regard to tumor-type specificity, possible
mechanisms of action and drug resistance and cell death in human tumor cell lines
and in 78 samples of tumor cells from patients using the fluorometric
microculture cytotoxicity assay and the automated fluorescence-imaging microscope
ArrayScan((R)). Disulfiram induced cytotoxicity in a biphasic pattern in both
cell lines and patient tumor cells. Disulfiram induced apoptosis as measured by
cell membrane permeability, nuclear fragmentation/condensation and caspase-3/7
activation using high content screening assays. For many of the cell lines tested
disulfiram was active in sub-micromolar concentrations. When comparing the
logIC(50) patterns with other cytotoxic agents, disulfiram showed low correlation
(R<0.5) with all drugs except lactacystin (R=0.69), a known proteasome inhibitor,
indicating that the two substances may share mechanistic pathways. Disulfiram was
more active in hematological than in solid tumor samples, but substantial
activity was observed in carcinomas of the ovary and the breast and in non-small
cell lung cancer. Disulfiram also displayed higher cytotoxic effect in cells from
chronic lymphocytic leukemia than in normal lymphocytes (p<0.05), which may
indicate some tumor selectivity. These results together with large clinical
experience and relatively mild side effects encourage clinical studies of
disulfiram as an anti-cancer agent.
PMID- 17026968
TI - EDG receptors as a potential therapeutic target in retinal ischemia-reperfusion
injury.
AB - LPA (lysophosphatidic acid) specific endothelial differentiation gene (EDG)
receptors have been implicated in various anti-apoptotic pathways. Ischemia of
the brain and retina causes neuronal apoptosis, which raises the possibility that
EDG receptors participate in anti-apoptotic signaling in ischemic injury. We
examined the expression of EDG receptors in a model of retinal ischemia
reperfusion injury and also tested LXR-1035, a novel analogue of LPA, in the rat
following global retinal ischemic injury. Rats were subjected to 45 or 60 min of
raised intraocular pressure. Animals were sacrificed at 24 h post-ischemia and
retinal tissue was stained for EDG receptors. In separate experiments, animals
were randomized to receive LXR or saline vehicle by intravitreal injection 24 h
prior to ischemia. The degree of retinal damage was assessed morphologically by
measuring the thickness of the inner retinal layers as well as functionally by
electroretinography (ERG). We found that the normal retina has a baseline
expression of the LPA receptors, EDG-2 and EDG-4, which are significantly
upregulated in the inner layers in response to ischemia. Animals pretreated with
LXR-1035 had dose-dependent, significant reductions in histopathologic damage and
significant improvement in functional deficits compared with corresponding
vehicle-controls, after 45 and 60 min of ischemia. These results suggest that LPA
receptor signaling may play an important role in neuroprotection in retinal
ischemia-reperfusion injury.
PMID- 17026969
TI - Aldehyde load in ischemia-reperfusion brain injury: neuroprotection by
neutralization of reactive aldehydes with phenelzine.
AB - In ongoing studies of the neuroprotective properties of monoamine oxidase
inhibitors, we found that phenelzine provided robust neuroprotection in the
gerbil model of transient forebrain ischemia, with drug administration delayed up
to 3 h post reperfusion. Since ischemia-reperfusion brain injury is associated
with large increases in the concentrations of reactive aldehydes in the penumbra
area, we investigated if the hydrazine function of phenelzine was capable of
sequestering reactive aldehydes. Both aminoaldehydes and acrolein are generated
from the metabolism of polyamines to putrescine by polyamine oxidase. These toxic
aldehydes in turn compromise mitochondrial and lysosomal integrity and initiate
apoptosis and necrosis. Previous studies have demonstrated that pharmacological
neutralization of reactive aldehydes via the formation of thioacetal derivatives
results in significant neuroprotection in ischemia-reperfusion injury, in both
focal and global ischemia models. In our studies of acrolein and 3-aminopropanal
toxicity, using an immortalized retinal cell line, we found that aldehyde
sequestration with phenelzine was neuroprotective. The neuroprotection observed
with phenelzine is in agreement with previous studies of aldehyde sequestering
agents in the treatment of ischemia-reperfusion brain injury and supports the
concept that "aldehyde load" is a major factor in the delayed cell losses of the
ischemic penumbra.
PMID- 17026970
TI - Extranuclear estrogen receptor beta immunoreactivity is on doublecortin
containing cells in the adult and neonatal rat dentate gyrus.
AB - In adult female rats, estrogen receptor (ER) activation, particularly of ERbeta,
promotes hippocampal neurogenesis. We previously reported that extranuclear
ERbeta immunoreactivity (ir) in adult rats is on cellular profiles in or near the
granule cell layer, which is the location of newly generated cells. During
development, cells in or near the granule cell layer transiently express high
levels of estrogen binding and nuclear ERs. Thus, we sought to determine if
extranuclear ERbeta is in newly generated cells in adult and neonatal rat dentate
gyrus. Sections from the dentate gyrus of adult proestrus or postnatal day 7 and
14 female rats were dual-labeled for ERbeta and the new-cell marker doublecortin
(DCX) and examined by electron microscopy. DCX-containing neurons were found in
the subgranular hilus in adult rats and were more widespread throughout the
granule cell layer and hilus of neonatal rats. In both adults and neonatal rats,
ERbeta immunoreactivity was found in a subset of DCX-labeled neurons. Electron
microscopic examination of the adult dentate gyrus revealed that most perikarya
with DCX-ir had the morphological characteristics of granule cells, although a
few resembled interneurons. Dendrites with DCX-ir also were observed. In both
adults and neonates, DCX-labeled neuronal perikarya and dendrites contained
ERbeta-ir; ERbeta-ir usually was aggregated near the plasma membrane,
mitochondria or endoplasmic reticula. ERbeta-ir was in glial profiles that
apposed DCX-labeled perikarya and dendrites. These findings are consistent with
data showing that estrogens can exert non-genomic effects directly and indirectly
on newly generated cells in neonatal and adult rat dentate gyrus.
PMID- 17026971
TI - Interaction of interleukin-1beta with muscarinic acetylcholine receptor-mediated
signaling cascade in cholinergically differentiated SH-SY5Y cells.
AB - Increased expression of interleukin (IL)-1beta has been found in Alzheimer brain,
raising the question whether plaque-associated up-regulation of IL-1beta may
contribute to neurodegeneration. IL-1beta is capable to induce a number of events
that also occur in Alzheimer's disease such as stimulation of the amyloidogenic
pathway of amyloid precursor protein processing. However, less is known on
participation of IL-1beta in specific cholinergic cell loss. To reveal whether IL
1beta affects muscarinic acetylcholine receptor (mAChR)-mediated intracellular
signaling, cholinergically differentiated SH-SY5Y cells were exposed to IL-1beta
for various periods of time followed by stimulation of mAChR with carbachol for 1
h, and key molecules of cholinergic signaling cascades were determined including
phosphoinositide hydrolysis, DNA-binding capacity of NFkappaB and AP-1, and
activity of acetylcholinesterase (AChE). Carbachol stimulation of SH-SY5Y cells
dose-dependently stimulated the activation of the transcription factors NFkappaB
and AP-1 as revealed by electrophoretic mobility shift assay (EMSA), while pre
exposure of SH-SY5Y cells for 24 h with 1 ng/ml IL-1beta completely suppressed
the carbachol response. mAChR-mediated enhancements of AChE activity by carbachol
were impaired following pre-exposure of SH-SY5Y cells with IL-1beta, already
detectable at a concentration of 1 ng/ml and 1 h of exposure time. The data
indicate that IL-1beta may interfere with the cholinergic signal transduction
cascade by inhibiting transcription factor activation, thus providing another
mechanism by which IL-1beta may induce cholinergic dysfunction in Alzheimer's
disease.
PMID- 17026972
TI - Why the Brugada syndrome is not yet a disease: syndromes, diseases, and genetic
causality.
PMID- 17026973
TI - Simvastatin improves left ventricular function after myocardial infarction in
hypercholesterolemic rabbits by anti-inflammatory effects.
AB - OBJECTIVES: Hypercholesterolemia contributes to coronary artery disease
progression but little is known about its effect on left ventricular (LV)
function after myocardial infarction (MI). The aim of this study was to
investigate the effects of hypercholesterolemia and statin treatment in rabbits
with experimental MI. METHODS AND RESULTS: New Zealand White rabbits on a normal
or cholesterol-rich diet for 4 weeks, underwent permanent coronary artery
ligation. Starting on the first day post-MI rabbits were treated with either
placebo or simvastatin (5 mg/kg/day) for 9 weeks. Hypercholesterolemia itself did
not affect LV function in sham-operated animals but further impaired LV systolic
(dP/dtmax -42%) and diastolic (dP/dtmin -47%) function in MI rabbits on placebo.
Simvastatin treatment not only prevented deterioration of LV function associated
with hypercholesterolemia but improved LV function (dP/dtmax +130%; dP/dtmin
+144%, P < 0.05). Simvastatin also attenuated the depression of LV function in
normocholesterolemic MI rabbits (dP/dtmax +46%; dP/dtmin +53%, P < 0.05).
Hypercholesterolemia in MI rabbits coincided with a significant increase in C
reactive protein levels (marker of inflammation) and Rac1-GTPase activity (marker
of oxidative stress), and a reduction in cardiac sarcoplasmic-reticulum calcium
ATPase-2 expression and endothelial nitric oxide synthase protein
phosphorylation, all of which were normalised by simvastatin treatment. Elevated
serum cholesterol levels were only partially reduced by simvastatin. CONCLUSIONS:
Hypercholesterolemia further impaired the depressed LV function in rabbits post
MI. Statin treatment reversed this effect, and conferred additional protection,
as in normocholesterolemic animals. Our study suggests that anti-inflammatory and
anti-oxidative effects of simvastatin substantially contribute to its beneficial
effects on cardiac function after MI.
PMID- 17026974
TI - Usefulness of monitoring free (unbound) concentrations of therapeutic drugs in
patient management.
AB - Drugs are bound to various serum proteins in different degrees and only unbound
or free drug is pharmacologically active. Although free drug concentration can be
estimated from total concentration, for strongly bound drugs, prediction of free
level is not always possible. Conditions like uremia, liver disease and
hypoalbuminemia can lead to significant increases in free drug resulting in drug
toxicity even if the concentration of total drug is within therapeutic range.
Drug-drug interactions may also lead to a disproportionate increase in free drug
concentrations. Elderly patients may have increased free drug concentrations due
to hypoalbuminemia. Elevated free phenytoin concentrations have also been
reported in patients with AIDS and pregnancy. Currently free drug concentrations
of anticonvulsants such as phenytoin, carbamazepine and valproic acid are widely
measured in clinical laboratories. Newer drugs such as mycophenolic acid mofetil
and certain protease inhibitors are also considered as candidates for monitoring
free drug concentration.
PMID- 17026975
TI - Brain natriuretic peptide limits myocardial infarct size dependent of nitric
oxide synthase in rats.
AB - BACKGROUND: Brain natriuretic peptide (BNP) has recently been shown to have a
cardioprotective effect in animal models of myocardial ischemia-reperfusion (I-R)
injury. We hypothesized that exogenous BNP limits myocardial infarction on nitric
oxide synthase pathway. METHODS: A rat model of myocardial I-R injury was
established by ligating the left descending coronary artery for 30 min and then
reperfusing for 2 h. BNP was injected with different dose 5 min after the
ligation and lasting for 145 min. The myocardial infarct size and the area at
risk of ischemia were measured by staining with triphenyltetrazolium chloride
(TTC) and Evans blue dye. To examine the role of nitric oxide synthase (NOS),
expression of eNOS in the left ventricle was analyzed by western blotting. Nomega
nitro-L-arginine methyl ester (L-NAME; 30 ug/kg), or S-methylisothiourea (SMT; 3
ug/kg) was administrated before I-R with or without BNP. RESULTS: The control
infarct-to-risk ratio was 45.1+/-1.72% (means+/-SE). BNP infused 5 min after
ischemia limited infarct size in a dosage-dependent manner, with maximal
protection observed at 0.01 ug/(kg min) (infarct-to-risk: 24.7+/-1.69%, P<0.01
vs. control), associated with a 10-fold increase of myocardial endothelial nitric
oxide synthase above the control value. Protection afforded by BNP was abolished
by L-NAME but not by SMT, suggesting the involvement of putative endothelial but
not inducible nitric oxide synthase activation. CONCLUSIONS: We conclude that
natriuretic peptide/NOS/NO signaling may constitute an important injury-limiting
mechanism in myocardium.
PMID- 17026976
TI - Learning about occlusion: initial assumptions and rapid adjustments.
AB - We examined 6-month-olds abilities to represent occluded objects, using a corneal
reflection eye-tracking technique. Experiment 1 compared infants' ability to
extrapolate the current pre-occlusion trajectory with their ability to base
predictions on recent experiences of novel object motions. In the first condition
infants performed at asymptote ( approximately 2/3 accurate predictions) from the
first occlusion passage. In the second condition all infants initially failed to
make accurate prediction. Performance, however, reached asymptote after two
occlusion passages. This is the first study that demonstrates such rapid learning
effects during an occlusion task. Experiment 2 replicates these effects and
demonstrates a robust memory effect extending 24h. In occlusion tasks such long
term memory effects have previously only been observed in 14-month-olds (Moore &
Meltzoff, 2004).
PMID- 17026977
TI - Apes know that hidden objects can affect the orientation of other objects.
AB - Four bonobos, seven gorillas, and six orangutans were presented with two small
rectangular boards on a platform. One of the boards had a piece of food under it
so that it acquired an inclined orientation whereas the other remained flat on
the platform. Subjects preferentially selected the inclined board. In another
experiment, subjects were initially presented with two inclined boards and a
transformation took place in which one of the boards fell flat to the platform
while the other remained inclined. Subjects also preferred the board that
remained inclined. Two additional experiments highlighted some of the possible
limitations of their reasoning in this task. Presented with two inclined boards,
one of which was visibly supported by a piece of wood, they failed to
systematically select the unsupported one whose only reason for being inclined
was the presence of the reward. Another experiment presented two rewards in each
trial (instead of the customary one) in one of the following two combinations:
large banana vs. small carrot or small banana vs. large carrot. Prior to the
test, E presented both rewards to the subject and then hid each of them under one
of the boards so that both boards were differentially inclined due to the
different sizes of the rewards involved. Although subjects selected the board
that showed a greater inclination (thus securing the larger reward), they
disregarded the type of food that was involved. This often meant that they chose
the large carrot over the small banana even though they reversed such a choice
when the rewards were not occluded by the boards. Providing subjects with a
'reminder' of the type of reward hidden under the boards did not alter the
original results. There was no evidence of learning throughout the various
experiments and control tests ruled out the possibility of inadvertent cuing by
the experimenter, poor performance due to a lack of motivation, or good
performance due to a predisposition to select objects with sloped surfaces. It is
concluded that subjects made some inferences about the reason for the inclined
orientation of the boards, and not simply associated an inclined orientation with
the presence of the reward.
PMID- 17026978
TI - Long-term signal detection, segmentation and summarization using wavelets and
fractal dimension: a bioacoustics application in gastrointestinal-motility
monitoring.
AB - The current paper describes a wavelet-based method for long-term processing and
analysis of gastrointestinal sounds (GIS). Windowing techniques are used to
select sequential blocks of the prolonged multi-channel recordings and proceed to
various wavelet-domain processing stages. De-noising, significant-activity
detection, automated segmentation and extraction of summary curves are applied in
an integrated mode, allowing for enhanced content manipulation and analysis. The
proposed analysis scheme combines flexible long-term graphical representation
tools, while maintaining the ability of quick browsing via visualization and
auralization of the detected short-term events. This work is part of a project
aiming to implement non-invasive diagnosis over gastrointestinal-motility (GIM)
physiology. However, the proposed techniques might be applied to any study of
long-term bioacoustics time series.
PMID- 17026979
TI - Beneficial effect of intracellular free high-mannose oligosaccharides on
cryopreservation of mammalian cells and proteins.
AB - The cryoprotective effect of intracellular free high-mannose oligosaccharides
(HMOS) on mammalian cells and proteins was examined by monitoring PC-12 cell
viability and assaying protein kinase C (PKC)-epsilon activity. 1
Deoxymannojirimycin, an inhibitor of alpha-mannosidase, to cause an increase in
intracellular free HMOS, significantly rescued PC-12 cells with 2-h freezing
insult at -15 degrees C in a concentration (1-50mM)- and pretreatment time (48
72h)-dependent manner, as compared with unpretreated cells; full rescue from
freezing injury was obtained with 1-deoxymannojirimycin at more than 25mM for 48
h pretreatment and more than 3mM for 72- and 96-h pretreatment. For PC-12 cells
pretreated with 1-deoxymannojirimycin at 1mM for 72h, thawed cell viability after
more than 8-w cryopreservation at -80 degrees C in 10% (v/v) dimethyl sulfoxide
was much higher than that for cells without pretreatment. PKC-epsilon activity
was well preserved after 16-h cryopreservation at -20 degrees C in the presence
of mannose 9-N-acetylglucosamine 2 (Man9-GlcNAc2) (1 mM), an HMOS, while the
activity was reduced to 15% without Man9-GlcNAc2. Collectively, the results of
the present study suggest that intracellular free HMOS is a key molecule to
protect mammalian cells and proteins from freezing injury; in other words, HMOS
could be a new target for cryopreservation of mammalian cells and proteins.
PMID- 17026980
TI - Mechanisms of gonadal morphogenesis are not conserved between chick and mouse.
AB - To understand mechanisms of sex determination, it is important to know the
lineage relationships of cells comprising the gonads. For example, in mice, the Y
linked gene Sry triggers differentiation of Sertoli cells from a cell population
originating in the coelomic epithelium overlying the nascent gonad that also
gives rise to uncharacterised interstitial cells. In contrast, little is known
about origins of somatic cell types in the chick testis, where there is no Sry
gene and sex determination depends on a ZZ male/ZW female mechanism. To
investigate this, we performed fate mapping experiments in ovo, labelling at
indifferent stages the coelomic epithelium by electroporation with a lacZ
reporter gene and the underlying nephrogenous (or mesonephric) mesenchyme with
chemical dyes. After sex differentiation, LacZ-positive cells were exclusively
outside testis cords and were 3betaHSD-negative, indicating that the coelomic
epithelium contributes only to non-steroidogenic interstitial cells. However, we
detected dye-labelled cells both inside and outside the cords. The former were
AMH-positive while some of the latter were 3betaHSD-positive, showing that
nephrogenous mesenchyme contributes to both Sertoli cells and steroidogenic
cells. This is the first demonstration via lineage analysis that steroidogenic
cells originate from nephrogenous mesenchyme, but the revelation that Sertoli
cells have different origins between chick and mouse suggests that, during
evolution, mechanisms of gonad morphogenesis may diverge alongside those of sex
determination.
PMID- 17026981
TI - Fgf signaling negatively regulates Nodal-dependent endoderm induction in
zebrafish.
AB - In zebrafish development, Nodal signaling is critical for the induction of
endoderm and mesoderm. Three transcription factors downstream of Nodal, Bonnie
and Clyde (Bon), Faust (Fau)/Gata5 and Casanova (Cas), are required for endoderm
induction. However, it is not yet fully understood how the Nodal signaling
pathway regulates the decision process of endoderm and mesoderm induction. In
this study, we focused on Fgf signaling, downstream of Nodal signaling, during
endoderm induction. We found that activation of Fgf signaling decreases the
number of cas-expressing endodermal cells. Conversely, inhibition of this
signaling increases the number of endodermal cells without affecting the
expression of Nodal, Nodal antagonists, bon or fau/gata5. Inhibition of Fgf
signaling in endoderm mutants suggests that this signaling negatively regulates
cas expression by a pathway parallel to Bon and Fau/Gata5 in the molecular
cascade leading to endoderm. Furthermore, activation of Fgf signaling can
overcome Cas-mediated abrogation of mesodermal gene expression. Altogether, these
results suggest that Fgf signaling negatively regulates endoderm induction,
possibly through repression of cas expression and down-regulation of Cas
function.
PMID- 17026982
TI - VCAM-1 inhibits TGFbeta stimulated epithelial-mesenchymal transformation by
modulating Rho activity and stabilizing intercellular adhesion in epicardial
mesothelial cells.
AB - Regulation of epithelial-mesenchymal transformation (EMT) is of central
importance both in normal development and in disease. During heart development,
cells of the superficial epicardial mesothelium undergo EMT to give rise to
precursor cells of the coronary vasculature and cardiac fibroblasts. Here we
report that the alpha(4)beta(1) integrin ligand, VCAM-1, inhibits EMT of chick
epicardial mesothelial cells stimulated by TGFbeta isoforms. We further
investigated the molecular basis of this inhibition using cultured chick
embryonic and rat adult epicardial mesothelial cells. We observed that VCAM-1
increased cortical actin filaments at intercellular junctions and reduced stress
fibers across epicardial cells. VCAM-1 inhibited stress fiber formation by
TGFbeta1, TGFbeta2, TGFbeta3 and lysophosphatidic acid and altered Rho activity
stimulated by TGFbeta3. This was accompanied by an increase in tyrosine
phosphorylation of p190RhoGAP. All three TGFbeta isoforms weakened intercellular
adhesion, reduced membrane localization of beta-catenin and E-cadherin and
stimulated epicardial EMT in chick hearts. Each of these effects was restricted
by simultaneous VCAM-1 treatment. Our data support the hypothesis that VCAM-1 can
alter epicardial EMT at two key points: it limits Rho-dependent events such as
stress fiber formation and it maintains the association of beta-catenin and E
cadherin with the adherens junction.
PMID- 17026983
TI - Gli2 and Gli3 play distinct roles in the dorsoventral patterning of the mouse
hindbrain.
AB - Sonic Hedgehog (Shh) signaling plays a critical role during dorsoventral (DV)
patterning of the developing neural tube by modulating the expression of neural
patterning genes. Overlapping activator functions of Gli2 and Gli3 have been
shown to be required for motoneuron development and correct neural patterning in
the ventral spinal cord. However, the role of Gli2 and Gli3 in ventral hindbrain
development is unclear. In this paper, we have examined DV patterning of the
hindbrain of Shh(-/-), Gli2(-/-) and Gli3(-/-) embryos, and found that the
respective role of Gli2 and Gli3 is not only different between the hindbrain and
spinal cord, but also at distinct rostrocaudal levels of the hindbrain.
Remarkably, the anterior hindbrain of Gli2(-/-) embryos displays ventral
patterning defects as severe as those observed in Shh(-/-) embryos suggesting
that, unlike in the spinal cord and posterior hindbrain, Gli3 cannot compensate
for the loss of Gli2 activator function in Shh-dependent ventral patterning of
the anterior hindbrain. Loss of Gli3 also results in a distinct patterning defect
in the anterior hindbrain, including dorsal expansion of Nkx6.1 expression.
Furthermore, we demonstrate that ventral patterning of rhombomere 4 is less
affected by loss of Gli2 function revealing a different requirement for Gli
proteins in this rhombomere. Taken together, these observations indicate that
Gli2 and Gli3 perform rhombomere-specific function during DV patterning of the
hindbrain.
PMID- 17026984
TI - The bradykinin B2 receptor antagonist icatibant (Hoe 140) blocks aminopeptidase N
at micromolar concentrations: off-target alterations of signaling mediated by the
bradykinin B1 and angiotensin receptors.
AB - The N-terminal sequence of icatibant, a widely used peptide antagonist of the
bradykinin B(2) receptors, is analogous to that of other known aminopeptidase N
inhibitors. Icatibant competitively inhibited the hydrolysis of L-Ala-p
nitroanilide by recombinant aminopeptidase N (K(i) 9.1 microM). In the rabbit
aorta, icatibant (10-30 microM) potentiated angiotensin III, but not angiotensin
II (contraction mediated by angiotensin AT(1) receptors), and Lys-des-Arg(9)
bradykinin, but not des-Arg(9)-bradykinin (effects mediated by the bradykinin
B(1) receptors), consistent with the known susceptibility of these agonists to
aminopeptidase N. At concentrations possibly reached in vivo (e.g., in kidneys),
icatibant alters physiological systems different from bradykinin B(2) receptors.
PMID- 17026986
TI - N-acetylcysteine attenuates TNF-alpha-induced human vascular endothelial cell
apoptosis and restores eNOS expression.
AB - The circulatory inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is
increased in pathological conditions, such as diabetes, which initiate or
exacerbate vascular endothelial injury. Both nitric oxide (NO) and reactive
oxygen species may play a dual role (i.e., inhibiting or promoting) in TNF-alpha
induced endothelial cell apoptosis. We investigated the effects of the
antioxidant N-acetylcysteine on TNF-alpha-induced apoptosis in human vascular
endothelial cell (cell line ECV304) apoptosis, NO production and lipid
peroxidation. Cultured vascular endothelial cell (ECV304) were either not treated
(control), or treated with TNF-alpha (40 ng/ml) alone or TNF-alpha in the
presence of N-acetylcysteine at 30 mmol/l or 1 mmol/l, respectively, for 24 h.
Cell viability was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
diphenyltetrazolium bromide) assay. Cell apoptosis was assessed by flow
cytometry. TNF-alpha-induced endothelial cell apoptosis was associated with
increased inducible NO synthase but reduced endothelial NO synthase (eNOS)
protein expression. NO production and the levels of the lipid peroxidation
product malondialdehyde were concomitantly increased. Treatment with NAC at 30
mmol/l restored eNOS expression and further increased NO production as compared
to TNF-alpha alone, resulting in improved cell viability and reduced apoptosis.
This was accompanied by increased superoxide dismutase activity, increased
glutathione peroxidase production and reduced malondialdehyde levels. N
acetylcysteine at 1 mmol/l, however, did not have significant effects on TNF
alpha-induced endothelial cell apoptosis and cell viability despite it slightly
enhanced glutathione peroxidase production. N-acetylcysteine attenuation of TNF
alpha-induced human vascular endothelial cell apoptosis is associated with the
restoration of eNOS expression.
PMID- 17026985
TI - p38 mitogen-activated protein kinase inhibitor SB203580 reverses the
antianalgesia induced by dextro-morphine or morphine in the mouse spinal cord.
AB - We have previously demonstrated that intrathecal pretreatment with dextro
morphine or morphine attenuates the morphine-produced antinociception. The
phenomenon has been defined as antianalgesia, which is mediated by a non-opioid
receptor [Wu, H., Thompson, J., Sun, H., Terashvili, M., Tseng, L.F., 2005.
Antianalgesia: stereo-selective action of dextro-morphine over levo-morphine on
glia in the mouse spinal cord. J. Pharmacol. Exp. Ther. 314, 1101-1108]. To
determine if p38 mitogen-activated protein kinase (MAPK) is involved in the
antianalgesia, the effects of p38 MAPK inhibitor 4-(4-fluorophenyl)-2-(4
methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) on the attenuation of
the morphine-produced tail-flick inhibition induced by dextro-morphine or
morphine were studied in male CD-1 mice. Intrathecal pretreatment with SB203580
(24.2 nmol) reversed the attenuation of the morphine-produced tail-flick
inhibition induced by dextro-morphine (33 fmol) or morphine (0.3 nmol)
pretreatment. The finding indicates that the antianalgesia induced by dextro
morphine or morphine is mediated by the activation of p38 MAPK in the mouse
spinal cord.
PMID- 17026987
TI - Specific down-regulation of spinal mu-opioid receptor and reduced analgesic
effects of morphine in mice with postherpetic pain.
AB - The analgesic effects of opioid agonists and the expression of mu- and kappa
opioid receptors were compared between mice with herpetic pain and those with
postherpetic pain induced by herpetic virus inoculation. Morphine inhibited
herpetic pain more effectively than postherpetic pain. Intrathecal injection
reduced the analgesic effects of morphine on postherpetic pain, but
intracerebroventricular injection did not. The kappa-opioid receptor agonist
nalfurafine suppressed herpetic and postherpetic pain to similar degrees. mu
Opioid receptor-like immunoreactivities in the lumbar dorsal horn were markedly
decreased at the postherpetic, but not herpetic, stage of pain. In the dorsal
root ganglia, the expression of mu-opioid receptor mRNA was significantly
decreased in mice with postherpetic pain, whereas the kappa-opioid receptor mRNA
level was not altered. These results suggest that specific down-regulation of the
mu-opioid receptor in the primary sensory neurons is responsible for the reduced
analgesic action of morphine on postherpetic pain. The kappa-opioid receptor may
be a useful target for the analgesic treatment of postherpetic neuralgia.
PMID- 17026988
TI - Anti-hyperlipidemic properties of CM108 (a flavone derivative) in vitro and in
vivo.
AB - Peroxisome proliferator-activated receptors (PPARs) and liver X receptor alpha
are ligand-activated transcription factors that belong to nuclear receptors
superfamily and are involved in the regulation of lipid metabolism. PPAR,
especially PPAR-alpha, PPAR-gamma agonists and liver X receptor alpha agonists
can regulate the expression or biosynthesis of some factors involved in the
formation and function of HDL, such as apolipoprotein (apo) A-I and ATP binding
cassette transporter A1 (ABCA1). It is well known that HDL plays an important
role in the treatment of hyperlipidemia as the carrier of reverse cholesterol
transport. In the present study, the anti-hyperlipidemic properties of CM108, a
derivative of flavone, 9-Hydroxy-2-mercapto-6-phenyl-2-thioxo-1,3,5-trioxa
2lambda(5)-phospha-cyclopenta[b]naphthalen-8-one, were studied. Through the
transactivation assays of in vitro study, it was discovered that CM108 could
activate PPAR-alpha PPAR-gamma and liver X receptor alpha at 40-150 microg/ml,
which subsequently resulted in activating ABCA1 promoter and enhancing apoA-I and
apoA-II production, whereas reducing apoC-III production significantly.
Furthermore, after in vivo study that the hyperlipidemic rats were treated with
CM108 for 4 weeks, a significant increase was found in HDL cholesterol levels
(26.7%, P<0.05) and a significant decrease was also noticed in triglyceride
levels (26.3%, P<0.01) at 100 mg/kg CM108 group compared with that of control
animals. Meanwhile, the atherogenicity index, represented by total
cholesterol/HDL ratio, was significantly reduced (P<0.01). In conclusion, CM108
can effectively elevate HDL levels and lower triglyceride levels in
hyperlipidemic rats maybe by regulating a series of genes, receptors and proteins
related to HDL.
PMID- 17026989
TI - Roles of stretch-activated cation channel and Rho-kinase in the spontaneous
contraction of airway smooth muscle.
AB - In guinea pigs, it is well-known that mechanical stretch of airway smooth muscle
exhibits spontaneous tone which is mediated by cyclooxygenase (COX) activation.
We tested the hypothesis that this spontaneous contraction of airway smooth
muscle is mediated by stretch-activated non-selective cation channels and the
Rho/Rho-kinase pathway, as well as COX-2 using a pharmacological approach.
Isometric force and intracellular Ca(2+) concentrations ([Ca(2+)](i)) were
assessed in isolated guinea pig tracheal smooth muscle tissues. The samples were
stretched to a given level and the muscle behavior was monitored under isometric
conditions. We observed an increase in [Ca(2+)](i) and subsequent force
generation over a 15-min period. The augmented [Ca(2+)](i) and spontaneous
contraction due to the stretch were markedly attenuated by application of Gd(3+),
an inhibitor of stretch-activated channels, and removal of extracellular Ca(2+).
In contrast, nifedipine only had a mild inhibitory effect on the contraction. (R)
(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexane-carboxamide (Y-27632; a Rho
kinase inhibitor) abolished the spontaneous contraction with no changes in
[Ca(2+)](i). Simvastatin, which down-regulates Rho activity, also significantly
inhibited the contraction. Moreover, indomethacin, an inhibitor of COX-1 and -2,
and N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398; a COX-2
inhibitor) abolished the stretch-induced contraction without affecting
[Ca(2+)](i), whereas the inhibitory effect of 5-(4-chlorophenyl)-1-(4
methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC560; a COX-1 inhibitor) on the
contraction was much less. These findings demonstrated that Ca(2+) entry via
stretch-activated channels, the Rho/Rho-kinase pathway, and COX-2 are involved in
the mechanotransduction in guinea pig tracheal smooth muscle. Additionally, while
the Rho/Rho-kinase pathway and COX-2 regulate the spontaneous contraction
independently of [Ca(2+)](i), COX-1 is not involved in the stretch-induced force
generation.
PMID- 17026990
TI - Piceatannol stimulates osteoblast differentiation that may be mediated by
increased bone morphogenetic protein-2 production.
AB - Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene) is a polyphenol present in
grapes and wine. By means of alkaline phosphatase activity and osteocalcin enzyme
linked immunosorbent assay (ELISA), we have shown that piceatannol exhibits a
significant induction of differentiation in immortalized fetal osteoblasts
(hFOB), and osteosarcoma cells (MG-63). Alkaline phosphatase and osteocalcin are
phenotypic markers for early-stage differentiated osteoblasts and terminally
differentiated osteoblasts, respectively, our results indicate that piceatannol
stimulate osteoblast differentiation at various stages (from maturation to
terminally differentiated osteoblasts). Induction of differentiation by
piceatannol was associated with increased bone morphogenetic protein-2 (BMP-2)
production. Addition of purified BMP-2 protein did not increase the upregulation
of alkaline phosphatase activity and osteocalcin secretion by piceatannol,
whereas the BMP-2 antagonist noggin blocked piceatannol and BMP-2-mediated
alkaline phosphatase activity, and osteocalcin secretion enhancement, indicating
that BMP-2 production is required in piceatannol-mediated osteoblast maturation
and differentiation. In conclusion, piceatannol increased BMP-2 synthesis, and
this effect may contribute to its action on the induction of osteoblasts
maturation and differentiation, followed by an increase of bone mass. Decreases
in new bone formation, followed by estrogen deficiency or various pathologic
factors, may contribute to the mechanisms involved in postmenopausal
osteoporosis.
PMID- 17026991
TI - mGlu5 receptors are involved in the discriminative stimulus effects of self
administered ethanol in rats.
AB - Recent work has identified a role for metabotropic glutamate receptor subtype 5
(mGlu(5)) in the discriminative stimulus properties of investigator-administered
ethanol. The purpose of this study was to determine if mGlu(5) receptors modulate
the discriminative stimulus properties of self-administered ethanol. Results show
that the mGlu(5) receptor antagonist 6-Methyl-2-(phenylethynyl)pyridine (MPEP; 10
mg/kg) inhibited the discriminative stimulus properties of consumed ethanol
during a self-administration test session. Further, 10 mg/kg MPEP increased and 1
mg/kg MPEP decreased the amount of self-administered ethanol required to produce
full substitution. These results indicate that mGlu(5) receptors are involved in
the expression of the discriminative stimulus properties of self-administered
ethanol.
PMID- 17026992
TI - N-tosyl-L-phenylalanyl-chloromethyl ketone reduces ceramide during hypoxic
ischemic brain injury in newborn rat.
AB - N-tosyl-L-phenylalanyl-chloromethyl ketone (TPCK) suppresses apoptosis and
protects neurons from damage in animal models. TPCK is thought to act by
inhibiting ceramide production by sphingomyelinase. Ceramide is a proapoptotic
intracellular signal that is involved in the cerebral ischemia. We wished to see
whether ceramide contributes to TPCK's neuroprotective effects in vivo. Seven-day
old rat pups had the right carotid arteries permanently ligated followed by 2.5 h
of hypoxia (8% oxygen). TPCK (10 mg/kg, n=62) or vehicle (n=63) was administered
by i.p. 5 min prior to hypoxia. The level of ceramide in brain cortex both in
lesioned and unlesioned hemispheres was measured at 8 h, 18 h, 24 h, 2 and 5 days
after hypoxia-ischemia using reversed phase high performance liquid
chromatography. The level of ceramide significantly increased due to hypoxic
ischemia at 18, 24 h and 2 days after hypoxia (P<0.05 or P<0.01) but not at 8 h
or 5 days after hypoxia as compared to the contralateral hemisphere or a sham
group. Pretreatment with TPCK reduced this increase. We also examined the level
of sphingomyelin and the activities of the ceramide synthesizing sphingomyelinase
enzymes by thin layer chromatography. The activities of acidic and neutral
sphingomyelinase significantly increased due to hypoxic ischemia at 24 h after
hypoxia. TPCK significantly reduced this increase (P<0.05 vs. vehicle) but did
not affect the level of sphingomyelin. The results are consistent with the
hypothesis that ceramide is involved in TPCK's neuroprotective effects in hypoxic
ischemic brain injury in the newborn rat.
PMID- 17026993
TI - Dexfenfluramine does not worsen but moderates progression of chronic hypoxia
induced pulmonary hypertension.
AB - This study shows for the first time, that dexfenfluramine, a 5-HT(2) receptor
agonist, attenuates the development of chronic hypoxia-induced pulmonary
hypertension. Chronic exposure to hypoxia, 4 weeks, induced hypoxic pulmonary
hypertension in adult rat as haemodynamic and cardiac measurements showed
significant modifications in right ventricle parameters (free wall right
ventricle thickness; pulmonary acceleration time and velocity time integral) in
chronic hypoxic control when compared to normoxic control animals. We observed
that free wall right ventricle thickness and pulmonary velocity time integral
were significantly less in chronic hypoxic rats treated with dexfenfluramine when
compared to chronic hypoxic control rats. Similarly, rats exposed to chronic
hypoxia exhibited an increase in both right ventricle pressure and weight by
comparison to normoxic control animals but those variations were significantly
diminished in dexfenfluramine-treated rats, indicating the moderating influence
exerted by dexfenfluramine on chronic hypoxia-induced pulmonary hypertension and
cardiac alterations. Thus, we report here the ability of dexfenfluramine to limit
chronic hypoxia-induced pulmonary hypertension, emphasizing the importance of the
time after the dexfenfluramine treatment discontinuation to assess the influence
of this 5-HT receptor agonist on the development of chronic hypoxia-induced
pulmonary hypertension.
PMID- 17026994
TI - Effect of levofloxacin on serum glucose concentration in rats.
AB - To clarify the mechanism of fluoroquinolone-induced abnormalities in blood
glucose, the effect of levofloxacin on serum glucose concentration was
investigated in rats. Rats received an intravenous injection of levofloxacin and
their arterial blood was sampled periodically. The serum glucose concentration
decreased after an injection of 100 mg/kg of levofloxacin, while it increased at
levofloxacin 300 mg/kg. The serum immunoreactive insulin concentration increased
as the dose of levofloxacin increased. The serum epinephrine concentration was
rapidly elevated by levofloxacin at 300 mg/kg. The serum histamine concentration
increased after injections of levofloxacin, 200 and 300 mg/kg. Diphenhydramine (1
mg/kg) antagonized the hyperglycemia induced by 300 mg/kg of levofloxacin. In an
in vitro study, the release of epinephrine from the adrenal medulla in the
presence of levofloxacin was determined. Levofloxacin (300 microg/ml) did not
affect epinephrine release from the adrenal medulla. Levofloxacin can induce
hypoglycemia and hyperglycemia in rats. Levofloxacin can promote histamine
release, leading to an increased serum epinephrine concentration and
hyperglycemia.
PMID- 17026995
TI - Antiaggressive effects of MPEP, a selective antagonist of mGlu5 receptors, in
agonistic interactions between male mice.
AB - mGlu5 receptors are highly concentrated in limbic brain structures involved in
motivational and emotional behaviours. This study describes the effects of 2
methyl-6-(phenylethylnyl)pyridine (MPEP; 5, 10, 15, 20 and 25 mg/kg, ip), a
selective antagonist of the mGlu5 receptors, on agonistic behaviour elicited by
isolation in male mice. Individually housed mice were exposed to anosmic
opponents in a neutral area 30 min after drug administration. Besides other
behaviours, the aggressive (threat and attack) and exploratory behaviours were
evaluated during 10 min using an ethologically based analysis. MPEP produced a
behavioural profile characterized by a notable decrement of offensive behaviours,
accompanied by a significant increase of exploratory behaviours (nonsocial
exploration and social investigation). These findings suggest a role for mGlu5
receptors in aggression modulation.
PMID- 17026996
TI - The motor-impairing effects of GABA(A) and GABA(B) agonists in gamma
hydroxybutyrate (GHB)-treated rats: cross-tolerance to baclofen but not
flunitrazepam.
AB - gamma-Hydroxybutyrate (GHB) is believed to function as a neurotransmitter in the
mammalian brain by binding to a GHB-specific binding site. In addition, GHB may
also indirectly enhance the neuroinhibitory actions of gamma-aminobutyric acid
(GABA) by converting to GABA at neuronal synapses. The purpose of the present
study was to examine the effects of representative GABA(A) and GABA(B) receptor
agonists in rats treated chronically with GHB. Using a rotorod apparatus, the
motor-impairing effects of GHB, the indirect GABA(A) receptor agonist,
flunitrazepam, and the direct GABA(B) receptor agonist, baclofen, were examined
before, during and after chronic treatment with 1000 mg/kg GHB, b.i.d. Prior to
chronic treatment, all three drugs produced dose-dependent decreases in motor
performance at low (8 rpm) and high (32 rpm) rotational speeds. Chronic treatment
with GHB significantly decreased the potency of baclofen at both speeds, but did
not alter the potency of either GHB or flunitrazepam. Following termination of
chronic treatment, the potency of baclofen increased significantly at both speeds
and returned to that observed prior to chronic treatment. These data indicate
that chronic treatment with GHB confers tolerance to a GABA(B) receptor agonist
under conditions in which tolerance is not conferred to a GABA(A) receptor
agonist. These findings are consistent with the in vivo behavioral profile of
GHB, which reveals a greater role for GABA(B) receptors than for GABA(A)
receptors in its behavioral effects.
PMID- 17026997
TI - In situ detection of global DNA hypomethylation in exfoliative urine cytology of
patients with suspected bladder cancer.
AB - Global DNA hypomethylation is a common phenomenon in bladder cancer. Therefore we
investigated whether it is possible to detect and assess global DNA
hypomethylation in bladder cancer using a specific monoclonal antibody for 5
methyl-cytosine. Cytospins from exfoliative urine cytology specimens of patients
with bladder cancer or a history of bladder cancer, control patients with benign
urological diseases and of young healthy volunteers were analyzed. Urothelial
carcinoma (UC) cells showed various degrees of nuclear destaining indicating
global DNA hypomethylation whereas all specimens from healthy volunteers showed
granular nuclear staining indicating regular methylation of repeated DNA
sequences. Lowest 5-methylcytosine immunostaining scores were observed in
carcinoma cells and a statistically significant difference was observed between
urothelial cells of healthy controls or patients with benign disease compared to
bladder cancer patients (p<0.01, p<0.05, respectively). In UC cases even
morphologically normal urothelial cells often displayed evident hypomethylation.
Likewise, in patients with a history of UC, but no cystoscopic evidence of
recurrence, morphologically non-malignant urothelial cells presented with some
degree of demethylation. Our results strongly support the hypothesis of early
global demethylation in bladder cancer. Immunocytochemical staining with the 5
methylcytosine antibody allows simultaneous individual assessment of nuclear
morphology and methylation status of a given sample.
PMID- 17026999
TI - The murine TRAIL receptor signals caspase-independent cell death through
ceramide.
AB - Death receptors such as the 55 kDa tumor necrosis factor (TNF) receptor (TNF-R55)
or Fas can initiate both apoptotic (caspase-dependent) and caspase-independent
routes to programmed cell death (PCD). Here, we demonstrate for the first time
that the single murine receptor for (TNF)-related apoptosis-inducing ligand
(mTRAIL-R2) can induce a caspase-independent form of PCD with necrosis-like
features in addition to apoptosis. Analysis of morphological and cellular
features of caspase-independent PCD in response to TRAIL and TNF suggests that
mTRAIL-R2 and TNF-R55 elicit caspase-independent PCD through similar pathways,
although without participation of cathepsins. Cells overexpressing acid
ceramidase (AC), an enzyme that metabolizes the sphingolipid ceramide, show
enhanced survival from TRAIL-induced caspase-independent PCD but not from
apoptosis, implicating a function of ceramide as a key mediator in caspase
independent PCD (but not apoptosis) induced by mTRAIL-R2. In concert with the
enhanced resistance of AC-overexpressing cells against caspase-independent PCD
induced by TNF, our results suggest that ceramide acts as a common mediator of
caspase-independent PCD caused by death receptors such as mTRAIL-R2 and TNF-R55.
PMID- 17026998
TI - Requirements for proximal tubule epithelial cell detachment in response to
ischemia: role of oxidative stress.
AB - Sublethal renal ischemia induces tubular epithelium damage and kidney
dysfunction. Using NRK-52E rat proximal tubular epithelial cells, we have
established an in vitro model, which includes oxygen and nutrients deprivation,
to study the proximal epithelial cell response to ischemia. By means of this
system, we demonstrate that confluent NRK-52E cells lose monolayer integrity and
detach from collagen IV due to: (i) actin cytoskeleton reorganization; (ii) Rac1
and RhoA activity alterations; (iii) Adherens junctions (AJ) and Tight junctions
(TJ) disruption, involving redistribution but not degradation of E-cadherin, beta
catenin and ZO-1; (iv) focal adhesion complexes (FAC) disassembly, entangled by
mislocalization of paxillin and FAK dephosphorylation. Reactive oxygen species
(ROS) are generated during the deprivation phase and rapidly balanced at recovery
involving MnSOD induction, among others. The use of antioxidants (NAC) prevented
FAC disassembly by blocking paxillin redistribution and FAK dephosphorylation,
without abrogating AJ or TJ disruption. In spite of this, NAC did not show any
protective effect on cell detachment. H(2)O(2), as a pro-oxidant treatment,
supported the contribution of ROS in tubular epithelial cell-matrix but not cell
cell adhesion alterations. In conclusion, ROS-mediated FAC disassembly was not
sufficient for the proximal epithelial cell shedding in response to sublethal
ischemia, which also requires intercellular adhesion disruption.
PMID- 17027000
TI - Thy-1, via its GPI anchor, modulates Src family kinase and focal adhesion kinase
phosphorylation and subcellular localization, and fibroblast migration, in
response to thrombospondin-1/hep I.
AB - Normal fibroblast subpopulations have differential surface expression of the GPI
linked raft protein Thy-1, which correlates with differences in cellular adhesion
and migration in vitro. Thrombospondin-1 (TSP-1) induces an intermediate state of
adhesion in fibroblasts and other cells which facilitates migration. TSP-1 and
the hep I peptide derived from the amino-terminal/heparin-binding domain of TSP-1
induce disassembly of cellular focal adhesions. Our lab previously reported that
the induction of focal adhesion disassembly in fibroblasts by TSP-1 or by hep I
requires surface expression of Thy-1, as well as lipid raft integrity and Src
family kinase (SFK) signaling. We now report that TSP-1/hep I-induced fibroblast
migration requires Thy-1 expression and FAK phosphorylation, and that following
TSP-1/hep I stimulation, Thy-1 associates with FAK and SFK in a lipid raft
dependent manner. Furthermore, the GPI anchor of Thy-1, which localizes the
protein to specific lipid raft microdomains, is necessary for hep I-induced FAK
and SFK phosphorylation, focal adhesion disassembly, and migration. This is the
first report of an association between Thy-1 and FAK. Thy-1 modulates SFK and FAK
phosphorylation and subcellular localization, promoting focal adhesion
disassembly and migration in fibroblasts, following exposure to TSP-1/hep I.
PMID- 17027002
TI - Expressions of Rac1, Tiam1 and Cdc42 in retinoblastoma.
AB - The Rho GTPases are the molecular regulators of the cell motility processes and
are involved in cell cycle progression and gene transcription. We studied the
expression of Rho-like GTPases molecules, particularly Rac, Tiam1 and cdc42, in
retinoblastoma and correlated these with clinicopathological parameters of the
tumors. Sixty-seven tumors were included which were divided in to two groups;
group A: tumors with optic nerve/choroidal/orbital invasion (n=35) and group B:
tumors with no invasion (n=32). Immunohistochemistry was done on paraffin
sections for all the proteins and were confirmed by Western blot on fresh tumor
samples. In group A tumors, Rac was positive in 10/35 (28%), cdc42 was positive
in 12/35 (34%) and Tiam1 was positive in 30/35 (85%) tumors. In group 2 tumors,
Rac was positive in 5/32 (15%), cdc42 was positive in 4/32 (12%) and Tiam1 was
positive in 30/32 (93%) tumors. Two groups (both invasive and non-invasive
tumors) showed decreased expression of Rac1 and cdc42 whereas Tiam1 was
significantly expressed in invasive tumors compared to non-invasive tumors
(P<0.0001). We observed a 70K cleavage product of Tiam1 along with an 110K
product by blotting in RB samples. Caspase-3 was also demonstrated in RB samples,
which showed Tiam1 cleavage products. This is the first study that showed the
expression patterns of Rac, cdc42 and Tiam1 in retinoblastoma tumors. Thus,
further studies are required to prove the involvement of caspase-3 in the
cleavage of Tiam1 in vitro in RB cells and to trace out alternative pathways
involved in tumor progression.
PMID- 17027003
TI - Clonorchis sinensis: codon usage in nuclear genes.
AB - Codon usage in Clonorchis sinensis was analyzed using 12,515 codons from 38
coding sequences. Total GC content was 49.83%, and GC1, GC2 and GC3 contents were
56.32%, 43.15% and 50.00%, respectively. The effective number of codons converged
at 51-53 codons. When plotted against total GC content or GC3, codon usage was
distributed in relation to GC3 biases. Relative synonymous codon usage for each
codon revealed a single major trend, which was highly correlated with GC content
at the third position when codons began with A or U at the first two positions.
In codons beginning with G or C base at the first two positions, the G or C base
rarely occurred at the third position. These results suggest that codon usage is
shaped by a bias towards G or C at the third base, and that this is affected by
the first and second bases.
PMID- 17027001
TI - Proteasome-dependent regulation of signal transduction in retinal pigment
epithelial cells.
AB - As in many other types of cells, retinal pigment epithelial (RPE) cells have an
active ubiquitin-proteasome pathway (UPP). However, the function of the UPP in
RPE remains to be elucidated. The objective of this study is to determine the
role of the UPP in controlling the levels and activities of transcription factors
hypoxia-inducible factor (HIF) and NF-kappaB. We inhibited the UPP with
proteasome-specific inhibitors and determined the activation of HIF and NF-kappaB
as well as the expression and secretion of pro-angiogenic factors. HIF-1alpha was
not detectable in ARPE-19 cells under normal culture conditions. However, when
proteasome activity was inhibited, HIF-1alpha accumulated in RPE in a time
dependent manner. Consistent with accumulation of HIF-1alpha in the cells, levels
of mRNA for vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2)
in RPE were up to 7-fold higher upon inhibition of the proteasome. Proteasome
inhibition was also associated with a 2-fold increase in levels of mRNA for
angiopoietin-1 (Ang-1). ARPE-19 cells secrete significant levels of VEGF under
normal culture conditions. Inhibition of proteasome activity increased the
secretion of VEGF by 2-fold. In contrast to the increase in HIF activity, NF
kappaB activation was reduced by proteasome inhibition. In addition, the
expression and secretion of monocyte chemoattractant protein-1 (MCP-1) by RPE
were substantially attenuated by the inhibition of proteasome activity. These
data demonstrate that the UPP plays an important role in modulating the
activities of HIF and NF-kappaB in the RPE. Consequences of an impairment of the
UPP include accumulation of HIF-1alpha and diminished NF-kappaB activation, which
lead to enhanced expression and secretion of pro-angiogenic factors and
attenuated expression of MCP-1. Taken together, these data predict that the
impairment of the UPP could lead to the development of AMD-related phenotypes.
PMID- 17027004
TI - Leishmania mexicana amazonensis: development of a peptide tag useful for labeling
and purifying biotinylated recombinant proteins.
AB - A number of peptide tags are available to facilitate the characterization of
recombinant proteins. We have tested the bacterial oxaloacetate decarboxylase
biotinylation domain for its efficacy in tagging recombinant proteins in vivo in
Leishmania. To achieve efficient biotinylation, Leishmania also had to be co
transformed with the gene for bacterial biotin protein ligase (birA gene
product). The recombinant chimeric protein could be detected on blots probed with
avidin-horseradish peroxidase and purified on immobilized monomeric avidin
resins.
PMID- 17027005
TI - Antigen receptor regulation of phosphoinositide-dependent kinase 1 pathways
during thymocyte development.
AB - Phosphoinositide-dependent kinase 1 (PDK1) is essential for T cell development
but little is know about the stimuli that regulate PDK1 signaling in vivo. The
thymus contains a heterogeneous mixture of cells at different stages of
development making it difficult to use biochemical techniques to examine the
activity of PDK1 pathways as thymocytes develop in situ. Herein, we use a single
cell assay to quantify activation of the PDK1 target kinase ribosomal S6 kinase 1
(S6K1) in different murine thymocyte subsets immediately ex vivo. This technique
allows an assessment of S6K1 activation as thymocytes respond to developmental
stimuli in vivo. These studies reveal that only a small percentage of thymocytes
show evidence for activation of PDK1 mediated signaling in situ. The thymic
subpopulations that contain active PDK1/S6K1 are those known to be responding to
signaling by the pre T cell receptor and the mature alpha/beta T cell antigen
receptor (TCR). Moreover, loss of antigen receptor signaling in T cell
progenitors that cannot rearrange their TCR beta locus prevents in vivo
activation of S6K1. The present data identifying antigen receptor signaling as a
key activator of PDK1 mediated signaling afford a molecular explanation for the
important role of this molecule in T cells.
PMID- 17027006
TI - Interaction of TPPP/p25 protein with glyceraldehyde-3-phosphate dehydrogenase and
their co-localization in Lewy bodies.
AB - TPPP/p25, a flexible unstructured protein, binds to tubulin and induces aberrant
microtubule assemblies. We identified hereby glyceraldehyde-3-phosphate
dehydrogenase (GAPDH) as a new interacting partner of TPPP/p25. The
immunoprecipitation and affinity chromatographic experiments with bovine brain
cell-free extract revealed that the interaction was salt and NAD(+) sensitive
while ELISA showed resistant and firm association of the two isolated proteins.
In transfected HeLa cells at low expression level of EGFP-TPPP/p25, while the
green fusion protein aligned at the microtubular network, GAPDH distributed
uniformly in the cytosol. However, at high expression level, GAPDH co-localized
with TPPP/p25 in the aggresome-like aggregate. Immunohistochemistry showed
enrichment of TPPP/p25 and GAPDH within the alpha-synuclein positive Lewy body.
PMID- 17027007
TI - Mechanisms of sexual selection: sexual swellings and estrogen concentrations as
fertility indicators and cues for male consort decisions in wild baboons.
AB - Male mate-guarding episodes ('consortships'), are taxonomically widespread, yet
costly to individual males. Consequently, males should bias consortships toward
females with whom the probability of conception is high. We combined data on
consortships with visual scoring of sexual swellings and assays of fecal estrogen
concentrations (fE) in a wild population of baboons (Papio cynocephalus) to test
the hypotheses that sexual swellings are reliable indicators of (1) within-cycle
timing of ovulation, (2) differences in conception probability among females that
differ in maturational stage, and (3) conceptive versus non-conceptive cycles of
parous females. We also evaluated whether adult males might rely on swellings or
other estrogen-dependent signals (e.g., fE) for mate-guarding decisions. We found
that sexual swellings reflected conception probability within and among cycles.
Adult males limited their consortships to the turgescent phase of cycles, and
consorted more with adult females than with newly cycling adolescents. The
highest ranking (alpha) males discriminated more than did males of other ranks;
they (1) limited their consortships to the 5-day peri-ovulatory period, (2)
consorted more with adult than with adolescent females, and (3) consorted more
with adult females on conceptive cycles than on non-conceptive cycles, all to a
greater extent than did males of other ranks. Male mate choice based on sexual
swellings and other estrogenic cues of fertility may result in sexual selection
on these female traits and enhance dominance-based reproductive skew in males.
Alpha males are the least constrained in their mating behavior and can best take
advantage of these cues to mate selectively.
PMID- 17027008
TI - The prefrontal cortex, gonadal hormones and memory.
PMID- 17027009
TI - Fast gas chromatographic/mass spectrometric determination of diuretics and
masking agents in human urine: Development and validation of a productive
screening protocol for antidoping analysis.
AB - An analytical procedure was developed for the fast screening of 16 diuretics
(acetazolamide, althiazide, amiloride, bendroflumethiazide, bumetanide, canrenoic
acid, chlorthalidone, chlorthiazide, clopamide, ethacrynic acid, furosemide,
hydrochlorthiazide, hydroflumethiazide, indapamide, triamterene,
trichlormethiazide) and a masking agent (probenecid) in human urine. The whole
method involves three analytical steps, including (1) liquid/liquid extraction of
the analytes from the matrix, (2) their reaction with methyl iodide at 70 degrees
C for 2 h to form methyl derivatives, (3) analysis of the resulting mixture by
fast gas chromatography/electron impact mass spectrometry (fast GC/EI-MS). The
analytical method was validated by determining selectivity, linearity, accuracy,
intra and inter assay precision, extraction efficiencies and signal to noise
ratio (S/N) at the lowest calibration level (LCL) for all candidate analytes. The
analytical performances of three extraction procedures and five combination of
derivatization parameters were compared in order to probe the conditions for
speeding up the sample preparation step. Limits of detection (LOD) were evaluated
in both EI-MS and ECNI-MS (electron capture negative ionization mass
spectrometry) modes, indicating better sensitivity for most of the analytes using
the latter ionization technique. The use of short columns and high carrier gas
velocity in fast GC/MS produced efficient separation of the analytes in less than
4 min, resulting in a drastic reduction of the analysis time, while a resolution
comparable to that obtained from classic GC conditions is maintained. Fast
quadrupole MS electronics allows high scan rates and effective data acquisition
both in scan and selected ion monitoring modes.
PMID- 17027010
TI - Reaction product analysis by high-performance liquid chromatography-solid-phase
extraction-nuclear magnetic resonance Application to the absolute configuration
determination of naturally occurring polyyne alcohols.
AB - The absolute configuration of secondary hydroxy functions of seven natural
occurring polyyne derivatives has been elucidated by the application of Mosher
method of diastereomeric methoxy-2-trifluoromethyl-phenylacetyl (MTPA) ester
formation. High-performance liquid chromatography with diode array detection
(HPLC-DAD) of the reaction mixture using a water/acetonitrile gradient allowed
monitoring the reaction progress. Coupling of high-performance liquid
chromatography to solid-phase extraction combined with nuclear magnetic resonance
(HPLC-SPE-NMR) was utilized to generate highly reproducible (1)H and (19)F NMR
data needed as input for the absolute configuration determination based on the
analysis of relative shift differences. Chromatographic peaks of reaction
substrates and reaction products bearing less 10mug analyte were trapped on SPE
cartridges with the aid of water as makeup solvent. Deuterated chloroform was
used to elute and transfer the peak content from the SPE to the 60mul flow cell
of a 500MHz NMR spectrometer. For each analyte (1)H NMR spectra were obtained
within 15min. Additionally (19)F NMR spectra were recorded for selected analytes
in the same timeframe. Based on the obtained NMR data, the absolute configuration
of all polyynes under investigation was successfully designated.
PMID- 17027011
TI - Development of an online two-dimensional nano-scale liquid chromatography/mass
spectrometry method for improved chromatographic performance and hydrophobic
peptide recovery.
AB - An online two-dimensional (2D) strong cation-exchange (SCX)/reversed-phase (RP)
nano-scale liquid chromatography/mass spectrometry (nanoLC/MS) method was
developed for improved separation and hydrophobic peptide recovery. Sharper and
more symmetric RP peaks were observed with the use of a "band re-focusing
method", in which an analytical RP column with more hydrophobicity than the RP
trap column was used in the system. To recover hydrophobic peptides still
unreleased from the SCX column after a conventional salt step gradient due to
hydrophobic interaction, a RP step gradient from 10% to 30% acetonitrile (ACN)
was applied to the SCX column in the presence of a high salt concentration
following the salt gradient. There were 301 unique hydrophobic E. coli peptides
identified from the RP fractions. These peptides, which were 19% of all E. coli
peptides identified from a 2D run, would not have been identified without the
application of the RP gradient to the SCX column.
PMID- 17027012
TI - Identification of complex mixtures of sphingolipids in the stratum corneum by
reversed-phase high-performance liquid chromatography and atmospheric pressure
photospray ionization mass spectrometry.
AB - Sphingolipids, such as ceramides and cerebrosides, are important molecules in the
formation and maintenance of the epidermal barrier to water vapor diffusion. In
this paper we explore a new method to identify the sphingolipids found in the
stratum corneum (SC), the outer layer of the epidermis, of House sparrows living
in Saudi Arabia using reversed-phase high-performance liquid chromatography
(HPLC) coupled with atmospheric pressure photo-ionization mass spectrometry (APPI
MS). First, using thin layer chromatography (TLC) we found that the SC contains
ceramides, cerebrosides, and free fatty acids along with smaller amounts of
cholesterol. Knowing the classes of sphingolipids present in the SC markedly
reduced the number of possible molecules present. Then, we identified each
sphingolipid molecule in our sample by both negative and positive mode of APPI
MS. We confirmed our identifications by generation of accurate mass data, and by
examination of MS/MS spectra for selected molecules. Using APPI-MS, we identified
7 families of cerebrosides, for a total of 97 molecular species, and 4 families
of ceramides, for a total of 79 molecules, in the SC of House sparrows, a wider
array than would be found in mammals. Carbon chain lengths of fatty acids in the
sphingolipids were longer than those that have been reported for mammalian SC;
chain lengths of over 40 carbons were common. We also compared our estimates of
the quantity of lipids in the SC obtained by HPLC/MS with those from TLC.
Estimates of the amount of total ceramides and cerebrosides using TLC differed
from those obtained by HPLC/MS by +0.95% and -2.5%, respectively. We conclude
that our protocol using reversed-phase HPLC and APPI-MS is an useful method of
analyzing complex mixtures of sphingolipids in the SC.
PMID- 17027013
TI - Monodisperse hollow titania nanospheres prepared using a cationic colloidal
template.
AB - Titania-coated polymeric nanoparticles were synthesized based on the cationic
colloidal particles which were prepared by surfactant-free emulsion
copolymerization of styrene and butylacrylate in the presence of a cationic
monomer, methacryloxyethyltrimethyl ammonium chloride (MOTAC) using
azobis(isobutylamidine)hydrochloride (AIBA) as an initiator. These cationic
particles were stabilized by poly(vinylpyrrolidone) (PVP). Then, these particles
were dispersed in ethanol and mixed with titanium(IV) butoxide. Negatively
charged titania precursors were rapidly hydrolyzed onto the cationic surfaces of
colloidal particles. Subsequently, the samples were heated to 450 degrees C to
form anatase TiO2 and to remove the colloidal template, which resulted in hollow
nanospheres. The hollow titania particles were characterized with zeta analyzer,
transmission electron microscopy, scanning electron microscopy, light scattering,
X-ray diffraction, thermogravimetric analysis and FT-IR.
PMID- 17027014
TI - Layered double hydroxides as potential chromate scavengers.
AB - The LDH of Ni with Fe, having the formula Ni(1-x)Fe(x)(OH)2(A(n-))(x/n)yH2O (A =
NO3-, Cl-; x = 0.25, 0.33), scavenges CrO4(2-) ions from solution throughout the
concentration range examined (0.00625-0.25 N). The CrO4(2-) uptake capacity is
independent of the anion in the starting LDH but is higher when x = 0.25 (3.60
meq g(-1)) as compared to x = 0.33 (2.40 meq g(-1)). These values are higher than
those observed for control compounds beta-Ni(OH)2 (1.86 meq g(-1)) and FeO(OH)
(1.26 meq g(-1)), which do not have any interlayer chemistry, showing that
chromate uptake takes place by its incorporation in the interlayer region by a
stoichiometric anion-exchange reaction, rather than by adsorption. Nevertheless,
the interaction between the LDH and the chromate ions is weak. The weak
interaction is due to the mismatch between the symmetry of the chromate ions and
the symmetry of the interlayer site, which introduces turbostratic disorder in
the chromate-intercalated LDHs. The chromate ions can be completely leached out
by soaking the LDH in a sodium carbonate solution.
PMID- 17027015
TI - Correlation between surface tension and critical temperatures of liquid metals.
AB - The inter-relationship of surface tension sigma, molar volume V, and critical
temperature Tc has been examined using experimental values for eighteen liquid
metals. Hard-sphere diameters a correlate with the equation a(5/2) = 8.9733 x 10(
19) V (sigma/Tc)(1/4) - 1.0459 x 10(-25). Unknown Tc may be estimated using
surface tension and liquid density values.
PMID- 17027016
TI - Relation between P-wave dispersion and left ventricular geometric patterns in
newly diagnosed essential hypertension.
AB - AIM: P-wave durations and P-wave dispersion (PD) are considered to reflect the
heterogeneous conduction in atria. The aim of this study was to investigate PD
and P-wave duration in different left ventricle geometric patterns of
hypertensive patients. METHODS: One hundred forty-nine consecutive patients with
newly diagnosed essential hypertension and 29 healthy control groups were
included in the study. The maximum and minimum P-wave duration (Pmax and Pmin,
respectively) and PD were measured from the 12-lead surface electrocardiogram.
Echocardiographic examination was also performed in all subjects. Four different
geometric patterns were identified in hypertensive patients according to left
ventricular mass index (LVMI) and relative wall thickness. RESULTS: P-wave
dispersion was longer in concentric remodeling (CR), concentric hypertrophy (CH),
and eccentric hypertrophy (EH) groups when compared with the control group (P =
.009, P < .001, P < .001, respectively). P-wave dispersion of normal left
ventricle (NLV) geometric pattern was not different from that of the control
group. Patients with NLV geometric pattern had shorter PD than patients who had
CH and EH (NLV vs CH, P < .001; NLV vs EH, P = .025). P-wave dispersion of the
NLV group was not different from that of the CR group. Patients with CR had also
shorter PD than patients who had CH (P = .002). In bivariate analysis, there was
a significant correlation between PD with left ventricle geometry, body surface
area, LVMI, and relative wall thickness. In multiple linear regression analysis,
PD was independently correlated only with LVMI (beta = .425, P < .001).
CONCLUSIONS: P-wave dispersion is independently associated with LVMI rather than
left ventricle geometry and relative wall thickness in hypertensive patients.
Thus, it is increased particularly in patients with CH and EH.
PMID- 17027017
TI - Effect of clinical variables on the correlation between amount of ST elevation
and myocardial scintigraphic perfusion defect during coronary occlusion.
AB - PURPOSE: We investigated if the correlation between the amount of ST elevation
(STE) and myocardial ischemia could be altered by variables such as hypertension
or body mass index (BMI). METHODS: A 12-lead electrocardiogram and a technetium
99m tetrofosmin injection were performed during balloon coronary occlusion in 34
patients with single-vessel disease. RESULTS: The sum of STE correlated with
scintigraphic extent of ischemia (r = 0.441; P = .009), but this correlation
improved significantly in men and patients with BMI of 28 kg/m2 or less and was
highest in nonhypertensive patients (r = 0.763; P < .001). In contrast, it was
poor in women and patients with BMI greater than 28 kg/m2 or arterial
hypertension, being lowest in the latter subset (r = 0.110; P = .664). Moreover,
8 (80%) of 10 patients with extensive hypoperfusion but with low SigmaSTE (< or
=20 mm) were hypertensive. CONCLUSIONS: If confirmed by larger studies,
electrocardiographic underestimation of transmural ischemia during coronary
occlusion in patients with hypertension or increased BMI may lead to adjustments
in STE criteria for reperfusion therapy.
PMID- 17027018
TI - Electrocardiographic changes by accidental hypothermia in an urban and a tropical
region.
AB - BACKGROUND: Hypothermia is defined as a condition in which core temperature
(rectal, esophageal, or tympanic) reaches values below 35 degrees C. This may be
accidental, metabolic, or therapeutic. The accidental form is frequent in cold
climate countries and rare in those with tropical or subtropical climate. The aim
of this study was to evaluate electrocardiographic changes of patients with
accidental hypothermia. METHODS: In 59 patients with hypothermia, the following
electrocardiogram parameters were analyzed: rhythm and heart rate (HR), P-wave
characteristics, PR-interval duration, QRS-complex duration, presence of J wave
and its location characteristics, polarity, voltage, aspect and its correlation
with the degree of hypothermia, changes in T wave regarding its polarity and
characteristics, duration of the QT interval corrected for HR using both Bazett
and Friderica formulas, and possible presence of both supraventricular and
ventricular arrhythmias were independently and blindly analyzed in the tracings
by experienced cardiologists. RESULTS: In 6 patients, electrocardiogram was
normal. Sinus bradycardia was observed in 52.5% of the patients. J wave was
present in 51 patients, and its voltage correlated inversely and was
statistically significantly with the core temperature. Changes in T wave were
observed in 47.4% of the cases. QT interval, adjusted for HR, was prolonged in
72.8% of the cases. Idioventricular rhythm was found in 6 cases, total
atrioventricular block in 3 cases, and junctional rhythm and atrial fibrillation
in 2 patients. CONCLUSIONS: Electrocardiogram changes in accidental hypothermia
are frequent and characteristic for this entity improving diagnosis in usually
unconscious patients, and in many cases, it may be the diagnostic clue in
patients with conscience deficit in emergency units, even in patients from a
tropical climate where the population at risk may be exposed to temperatures
below 20 degrees C.
PMID- 17027019
TI - Characterization and incidence of inducible monomorphic ventricular tachycardia
in a postinfarction rabbit model.
AB - OBJECTIVE: Ventricular tachycardia (VT), occurring late after myocardial
infarction, is an important cause of sudden death. Animal models are useful for
the investigation of this arrhythmia. The aim of this study is to develop and
characterize a model of late postinfarction monomorphic VT in the rabbit. METHODS
AND RESULTS: Myocardial infarction was created by ligation of the left circumflex
artery. Cardiac electrophysiologic studies were performed 10 to 17 days
postinfarction in 39 rabbits, in 10 sham-operated rabbits, and 6 control rabbits.
Ventricular tachycardia was defined as a broad-complex tachycardia with a cycle
length of more than 100 milliseconds, a duration of more than 10 seconds, and
monomorphic QRS complexes. Using programmed stimulation, we induced VT in 9
rabbits (23%) in the infarct group but in none of the sham or control animals.
The mean infarct size was 23% +/- 9% (mean +/- SD) of the left ventricle.
CONCLUSION: Coronary ligation in the rabbit creates a substrate, which allows the
induction of sustained monomorphic VT with programmed stimulation. Monomorphic VT
is not inducible in rabbits without myocardial infarction. This model might allow
the testing of interventions that reduce the incidence of VT late after
myocardial infarction.
PMID- 17027020
TI - Production of calmodulin-tagged proteins in Drosophila Schneider S2 cells: a
novel system for antigen production and phage antibody isolation.
AB - We report the development of an expression system for the production of soluble,
calmodulin (CaM)-tagged proteins in Drosophila Schneider S2 cells and the
subsequent use of these proteins for the selection of phage displayed antibodies.
The CaM-tag permitted the purification of recombinant protein to >90% purity in a
single step at yields of >20 mg/l. Using platelet glycoprotein VI (GP6) as a
model, we demonstrated that the recombinant CaM-tagged protein was post
translationally N-glycosylated and had identical ligand specificity to native
protein. A novel selection strategy, exploiting the CaM tag, was then used to
isolate four single chain Fv fragments (scFvs) specific for GP6 from a non-immune
phage display library. In contrast to other selection methods, which can result
in antibodies that do not recognise native protein, all of the scFvs we selected
bound cell surface expressed GP6. In conclusion, the production of CaM-tagged
proteins in Drosophila Schneider S2 cells and the selection strategy reported
here offer advantages over previously published methods, including simple culture
conditions, rapid protein purification, specific elution of phage antibodies and
preferential selection of phage antibodies that recognise native, cell surface
expressed protein.
PMID- 17027021
TI - Amplification of the antigen-antibody interaction from quartz crystal
microbalance immunosensors via back-filling immobilization of nanogold on
biorecognition surface.
AB - A new quartz crystal microbalance immunoassay method based on a novel transparent
immunoaffinity reactor was developed for clinical immunoassay. To construct such
an affinity reactor, resonators with a frequency of 10 MHz were fabricated by
affinity binding of functionalized gold nanoparticles (nanogold) to quartz
crystal with immobilized specific ligand for the label-free analysis of the
affinity reaction between a ligand and its receptor. [Recombinant human tumor
markers, carcinoembryonic antigen (CEA) was chosen as a model ligand.] The
binding of target molecules onto the immobilized antibodies decreased the
sensor's resonant frequency, and the frequency shift was proportional to the CEA
concentration in the range of 3.0-50 ng/ml with a detection limit of 1.5 ng/ml at
a signal/noise ration of 3. A glycine-HCl solution (pH 2.3) was used to release
antigen-antibody complexes from the biorecognition surface. Good reusability was
exhibited. Moreover, spiking various levels of CEA into normal human sera was
diagnosed using the proposed immunoassay. Analytical results show the precision
of the developed immunoassay is acceptable, implying a promising alternative
approach for detecting CEA in clinical immunoassay. Compared with the
conventional enzyme-linked immunosorbent assay, the proposed immunoassay system
was simple and rapid without multiple labeling and separation steps. Importantly,
the proposed immunoassay system could be further developed for the immobilization
of other antigens or biocompounds.
PMID- 17027022
TI - Epizootiological studies of Amblyospora camposi (Microsporidia: Amblyosporidae)
in Culex renatoi (Diptera: Culicidae) and Paracyclops fimbriatus fimbriatus
(Copepoda: Cyclopidae) in a bromeliad habitat.
AB - The epizootiology of Amblyospora camposi was studied in a natural population of
Culex renatoi, a bromeliad-inhabiting mosquito, and its intermediate host,
Paracyclops fimbriatus fimbriatus, over a 2-year period. Twenty Eryngium cabrerae
plants were sampled monthly from January 2003 to January 2005 and the prevalence
of A. camposi in P.f. fimbriatus and Cx. renatoi populations was determined. The
monthly prevalence rates of meiospore infections in Cx. renatoi larvae never
exceeded 5.5% and was detected in 50% of the monthly samples. Meiospores were
available in plants over the course of the study at a mean concentration of 2 x
10(4) meiospores/ml. Within each plant the parasite was maintained by horizontal
transmission. P.f. fimbriatus with vegetative stages and mature spores were found
regularly in bromeliads suggesting efficient meiospore infectivity to field
copepod populations. The mean concentration of spores from copepods found in
plants was 8 x 10(2) spores/ml. Infections in copepods were detected in 54% of
the monthly samples with a prevalence rate ranging from 0.55 to 17.4% and an
overall average of 5.1%. Vegetative stages in fourth instar mosquito larvae
(probably derived from the horizontal pathway via spores formed in copepods) were
detected in 12.5% of the monthly samples with an overall prevalence rate of 1.1%.
Infections in female and male adults were detected in 20.8% of the monthly
samples with an overall average of 4.1% and 6.8%, respectively.
PMID- 17027023
TI - Molecular and phenotypic characterisation of Bacillus thuringiensis isolated
during epizootics in Cydia pomonella L.
AB - Twelve Bacillus thuringiensis strains were isolated from intestinal tracts of
Cydia pomonella larvae during epizootics in different laboratory insect culture
lines. Phenotypic and genetic similarity of these isolates, together with two
cultured from Leucoma salicis larvae and 14 reference B. thuringiensis strains
were determined. The epizootic bacteria did not form a single group based on
numerical analysis of biochemical properties. Simple RAPD method with only one
primer does not allow estimating the genetic similarity of B. thuringiensis
strains. We propose a novel strategy based on combining several DNA patterns
obtained by RAPD technique with different primers for B. thuringiensis typing.
Majority of infections in the C. pomonella culture lines were caused by bacteria
with different genotypes. However, two isolates cultured from infected insects at
different time (one strain was isolated in 1990 and the other in 1992) had
identical DNA fingerprint that suggested a possibility of these bacteria to
survive in the laboratory and to cause infections in different years. The results
of SDS-PAGE of whole-cell proteins revealed a possibility to apply protein
profile analysis in epidemiological investigations of infections caused by B.
thuringiensis. Strains with identical DNA patterns had very similar whole-cell
protein profiles.
PMID- 17027024
TI - Mechanical unloading of the heart activates the calpain system.
AB - The mechanism for the decrease in cardiomyocyte size with mechanical unloading is
unknown. The calpain system regulates cardiomyocyte atrophy. We obtained samples
from failing human hearts at the time of implantation and explantation of a left
ventricular assist device. For mechanical unloading, we also heterotopically
transplanted rat or mouse hearts for 1 week. The effect of calpain inhibition on
cardiac atrophy was assessed in transplanted hearts overexpressing calpastatin.
We measured transcript levels of calpain 1 and 2 in the human and the rodent
model, as well as calpain activity, a calpain-specific degradation product and
cardiomyocyte size in the two rodent models. Mechanical unloading of the failing
human heart significantly increased calpain 2 gene expression. Transcript levels
of calpain 1 and 2, calpain activity and a calpain-specific degradation product
all significantly increased in the unloaded rat heart. Unexpectedly, in hearts of
animals overexpressing calpastatin, cardiomyocyte size also decreased. Mechanical
unloading of the mammalian heart activates the calpain system, although other
proteolytic systems may compensate for decreased calpain activity when
calpastatin is overexpressed.
PMID- 17027026
TI - How does endothelin-1 cause a sustained increase in intracellular sodium and
calcium which lead to hypertrophy?
PMID- 17027025
TI - Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia
in rat hearts.
AB - Cardiac pathologies are associated with increased late INa that contributes to
the dysregulation of ion homeostasis and causes electrical and contractile
dysfunction. This study was designed to test the hypothesis that an increased
late sodium channel current (INa) leads to Ca2+ overload and left ventricular
(LV) dysfunction, and thereby inhibition of late INa (e.g., by ranolazine)
improves Ca2+ homeostasis and reduces LV dysfunction. Intracellular Ca2+
([Ca2+]i) and LV function were measured simultaneously in rat isolated perfused
hearts. Augmentation of late INa with sea anemone toxin-II (ATX-II, 12 nM)
increased diastolic [Ca2+]i (d[Ca2+]i), and impaired LV mechanical function, but
had no effect on [Ca2+]i transient amplitude. Although ranolazine (4 and 9
microM), an inhibitor of late INa, had no direct effects on d[Ca2+]i or LV
function, it significantly reduced the deleterious effects of ATX-II. Global
ischemia increased d[Ca2+]i and inhibited Ca2+ transient amplitude. During
reperfusion, Ca2+ transient amplitude recovered fully, but d[Ca2+]i remained
elevated and LV function was depressed, indicative of Ca2+ overload. Ranolazine
(9 microM) reduced d[Ca2+]i accumulation during ischemia as well as reperfusion
and improved recovery of LV function. These results show that augmentation of
late INa with ATX-II or by ischemia is associated with diastolic Ca2+ overload
and LV dysfunction. The beneficial effects of ranolazine in reducing Ca2+
overload and LV mechanical dysfunction during ischemia/reperfusion is consistent
with the inhibition of late INa mechanism of action.
PMID- 17027027
TI - Selective binding of meiosis-specific yeast Hop1 protein to the holliday
junctions distorts the DNA structure and its implications for junction migration
and resolution.
AB - Saccharomyces cerevisiae HOP1, which encodes a component of synaptonemal complex
(SC), plays an important role in both gene conversion and crossing over between
homologs, as well as enforces meiotic recombination checkpoint control over the
progression of recombination intermediates. In hop1Delta mutants, meiosis
specific double-strand breaks (DSBs) are reduced to 10% of the wild-type level,
and at aberrantly late times, these DSBs are processed into inter-sister
recombination intermediates. However, the underlying mechanism by which Hop1
protein regulates these nuclear events remains obscure. Here we show that Hop1
protein interacts selectively with the Holliday junction, changes its global
conformation and blocks the dissolution of the junction by a RecQ helicase. The
Holliday junction-Hop1 protein complexes are significantly more stable at higher
ionic strengths and molar excess of unlabeled competitor DNA than complexes
containing other recombination intermediates. Structural analysis of the Holliday
junction using 2-aminopurine fluorescence emission, DNase I footprinting and
KMnO4 probing provide compelling evidence that Hop1 protein binding induces
significant distortion at the center of the Holliday junction. We propose that
Hop1 protein might coordinate the physical monitoring of meiotic recombination
intermediates with the process of branch migration of Holliday junction.
PMID- 17027028
TI - Small-angle X-ray scattering reveals the solution structure of a
bacteriophytochrome in the catalytically active Pr state.
AB - Phytochromes are light-sensing macromolecules that are part of a two component
phosphorelay system controlling gene expression. Photoconversion between the Pr
and Pfr forms facilitates autophosphorylation of a histidine in the dimerization
domain (DHp). We report the low-resolution structure of a bacteriophytochrome
(Bph) in the catalytic (CA) Pr form in solution determined by small-angle X-ray
scattering (SAXS). Ab initio modeling reveals, for the first time, the domain
organization in a typical bacteriophytochrome, comprising an chromophore binding
and phytochrome (PHY) N terminal domain followed by a C terminal histidine kinase
domain. Homologous high-resolution structures of the light-sensing chromophore
binding domain (CBD) and the cytoplasmic part of a histidine kinase sensor allows
us to model 75% of the structure with the remainder comprising the phytochrome
domain which has no 3D representative in the structural database. The SAXS data
reveal a dimeric Y shaped macromolecule and the relative positions of the
chromophores (biliverdin), autophosphorylating histidine residues and the ATP
molecules in the kinase domain. SAXS data were collected from a sample in the
autophosphorylating Pr form and reveal alternate conformational states for the
kinase domain that can be modeled in an open (no-catalytic) and closed
(catalytic) state. This model suggests how light-induced signal transduction can
stimulate autophosphorylation followed by phosphotransfer to a response regulator
(RR) in the two-component system.
PMID- 17027029
TI - Thermus thermophilus bacteriophage phiYS40 genome and proteomic characterization
of virions.
AB - We determined the sequence of the 152,372 bp genome of phiYS40, a lytic tailed
bacteriophage of Thermus thermophilus. The genome contains 170 putative open
reading frames and three tRNA genes. Functions for 25% of phiYS40 gene products
were predicted on the basis of similarity to proteins of known function from
diverse phages and bacteria. phiYS40 encodes a cluster of proteins involved in
nucleotide salvage, such as flavin-dependent thymidylate synthase, thymidylate
kinase, ribonucleotide reductase, and deoxycytidylate deaminase, and in DNA
replication, such as DNA primase, helicase, type A DNA polymerase, and predicted
terminal protein involved in initiation of DNA synthesis. The structural genes of
phiYS40, most of which have no similarity to sequences in public databases, were
identified by mass spectrometric analysis of purified virions. Various phiYS40
proteins have different phylogenetic neighbors, including myovirus, podovirus,
and siphovirus gene products, bacterial genes and, in one case, a dUTPase from a
eukaryotic virus. phiYS40 has apparently arisen through multiple acts of
recombination between different phage genomes as well as through acquisition of
bacterial genes.
PMID- 17027030
TI - The alkali molten globule state of horse ferricytochrome c: observation of cold
denaturation.
AB - Here, we present the basic structural properties and the thermodynamic
description of a previously unknown alkali molten globule state of horse
"ferricytochrome c". Both sodium and guanidinium cations stabilize the alkali
denatured state at pH 13, presumably by a charge screening mechanism. The Na(+)
stabilized conformation (B state) clearly meets with the molecular organizational
definition of the generic molten globule state. The B state exhibits highly
cooperative thermal unfolding transitions monitored by both near and far-UV CD.
Analyses of these transitions show substantial heat capacity change, suggesting
that the hydrophobic effect contributes considerably to its energetic stability.
At low salt concentration where molten globules are less stable, the B state
undergoes reversible cold denaturation.
PMID- 17027031
TI - Structure and action of the binary C2 toxin from Clostridium botulinum.
AB - C2 toxin from Clostridium botulinum is composed of the enzyme component C2-I,
which ADP-ribosylates actin, and the binding and translocation component C2-II,
responsible for the interaction with eukaryotic cell receptors and the following
endocytosis. Three C2-I crystal structures at resolutions of up to 1.75 A are
presented together with a crystal structure of C2-II at an appreciably lower
resolution and a model of the prepore formed by fragment C2-IIa. The C2-I
structure was determined at pH 3.0 and at pH 6.1. The structural differences are
small, indicating that C2-I does not unfold, even at a pH value as low as 3.0.
The ADP-ribosyl transferase activity of C2-I was determined for alpha and
beta/gamma-actin and related to that of Iota toxin and of mutant S361R of C2-I
that introduced the arginine observed in Iota toxin. The substantial activity
differences between alpha and beta/gamma-actin cannot be explained by the protein
structures currently available. The structure of the transport component C2-II at
pH 4.3 was established by molecular replacement using a model of the protective
antigen of anthrax toxin at pH 6.0. The C-terminal receptor-binding domain of C2
II could not be located but was present in the crystals. It may be mobile. The
relative orientation and positions of the four other domains of C2-II do not
differ much from those of the protective antigen, indicating that no large
conformational changes occur between pH 4.3 and pH 6.0. A model of the C2-IIa
prepore structure was constructed based on the corresponding assembly of the
protective antigen. It revealed a surprisingly large number of asparagine
residues lining the pore. The interaction between C2-I and C2-IIa and the
translocation of C2-I into the target cell are discussed.
PMID- 17027032
TI - Mixed macromolecular crowding accelerates the refolding of rabbit muscle creatine
kinase: implications for protein folding in physiological environments.
AB - The effects of four single macromolecular crowding agents, Ficoll 70, dextran 70,
polyethylene glycol (PEG) 2000, and calf thymus DNA (CT DNA), and three mixed
crowding agents containing both CT DNA and polysaccharide (or PEG 2000) on the
refolding of guanidine hydrochloride-denatured rabbit muscle creatine kinase (MM
CK) have been examined by activity assay. When the total concentration of the
mixed crowding agent is 100 g/l, in which the weight ratio of CT DNA to Ficoll 70
is 1:9, the refolding yield of MM-CK after refolding for 3 h under these
conditions increases 23% compared with that in the presence of 10 g/l CT DNA, 18%
compared with 100 g/l Ficoll 70, and 19% compared with that in the absence of
crowding agents. A remarkable increase in the refolding yield of MM-CK by a mixed
crowding agent containing CT DNA and dextran 70 (or PEG 2000) is also observed.
Further folding kinetics analyses show that these three mixed crowding agents
remarkably accelerate the refolding of MM-CK, compared with single crowding
agents. Aggregation of MM-CK in the presence of any of the three mixed crowding
agents is less serious than that in the presence of a single crowding agent at
the same concentration but more serious than that in the absence of crowding
agents. Both the refolding yield and the refolding rate of MM-CK in mixtures of
these agents are increased relative to the individual agents by themselves,
indicating that mixed macromolecular crowding agents are more favorable to MM-CK
folding and can be used to reflect the physiological environment more accurately
than single crowding agents.
PMID- 17027033
TI - A mouse model of posttraumatic stress disorder that distinguishes between
conditioned and sensitised fear.
AB - The pathomechanisms of posttraumatic stress disorder (PTSD) are still unknown,
but both fear conditioning and stress sensitisation are supposed to play a
crucial role. Hence, valid animal models that model both associative and non
associative components of fear will facilitate elucidation of the biological
substrates of the illness, and to develop novel and specific approaches for its
prevention and therapy. Here we applied a single electric footshock to C57BL/6N
(B6N) and C57BL/6JOla (B6JOla) mice and recorded the conditioned response to
contextual trauma reminders (associative fear), the sensitised reaction to a
neutral tone in a novel environment (non-associative fear, hyperarousal), social
interaction and various emotional behaviours using Modified Holeboard, Test for
Novelty-Induced Suppression of Feeding and Forced Swimming Test, after different
incubation times (1, 14, 28 days). Freezing generally increased as a function of
shock intensity. In B6N mice, sensitised fear was maximal 28 days after trauma
and was accompanied by signs of emotional blunting and social withdrawal. B6JOla
mice, in contrast, were less susceptible to develop PTSD-like symptoms. The
phenotype of B6N exhibited high behavioural variance, allowing distinction
between vulnerable and resilient individuals. Only in vulnerable B6N mice,
chronic fluoxetine treatment - initiated after an incubation period of 28 days -
ameliorated sensitised fear. This new mouse model fulfils common criteria for
face and predictive validity and can be used to investigate the biological
correlates of individual fear susceptibility, as well as the impact and
interrelationship of associative and non-associative fear components in the
development and maintenance of PTSD.
PMID- 17027034
TI - Cambodian founder effect for spinocerebellar ataxia type 3 (Machado-Joseph
disease).
AB - Four families from the same region of Cambodia immigrated to the Pacific
Northwest of the United States. All four families have been discovered to have
spinocerebellar ataxia type 3 (SCA 3; Machado-Joseph disease) with a similar
clinical phenotype. CAG repeat expansions in the ATXN3 gene range from 72 to 77.
Mean age of onset has varied from 19 to 44 years and mean age at death of 4
individuals has been 60 years. The prevalence of the various subtypes of SCA
varies worldwide from country to country. Neurologists should be alert to the
possibility of SCA 3 in Cambodian patients with unexplained cerebellar ataxia.
PMID- 17027035
TI - Intrafamilial phenotypic and genetic heterogeneity of dystonia.
AB - Most cases of early-onset primary torsion dystonia are caused by the same 3-bp
(GAG) deletion in the DYT1 gene. We describe a large Serbian family with
significant intrafamilial variability of the DYT1 phenotype, from asymptomatic
carrier status to late-onset focal, and generalized jerky dystonia. Seven
mutation carriers (six proven by direct analysis and one by inferred haplotype)
were identified, but only two of them were affected by dystonia (penetrance
reduced to 29%). In addition, three GAG-deletion-negative family members also
developed dystonia (two multifocal dystonia and one torticollis), suggesting that
their involuntary movements are due to some other etiological factor(s) (i.e.,
another dystonia gene), or may be psychogenic.
PMID- 17027036
TI - Angiosperms (seagrass) within the EU water framework directive: a UK perspective.
AB - Taxonomic composition, the presence of disturbance-sensitive species and
abundance are attributes for monitoring the status of marine angiosperms; a
biological quality element required for assessment of environmental condition
under the Water Framework Directive (WFD). Their relevance for defining the
ecological status of UK water bodies and the establishment of reference
conditions for these attributes are described. Founded on quantitative
measurements of these attributes, a set of metrics has been developed for
monitoring and assessment of the only truly marine angiosperms, seagrass. The
proposed metrics are presented and tested against a variety of littoral and
sublittoral UK seagrass beds. In combination they express the cumulative response
of marine angiosperms to different levels of anthropogenic disturbance.
PMID- 17027037
TI - Survival under chronic stress from sediment load: spatial patterns of hard coral
communities in the southern islands of Singapore.
AB - Six reef sites were chosen along the west coast of the southern islands of
Singapore, at an increasing distance from the densely populated metropolitan
area, to study the spatial patterns of coral reef communities on the upper reef
slope ( approximately 4m) and the associated environmental conditions. Chronic
exposure to high sediment load was the most obvious form of anthropogenic stress.
Recruitment rates on ceramic tiles were low (1.4+/-1.0-20+/-14.7 recruits m(-2)
yr(-1)) but decreased towards the main island of Singapore as did hard coral
cover and coral density. Coral fauna consisted of genera generally found in
deeper waters (e.g., fungiids, foliose Oxypora, Leptoseris, and Echinopora) or
those well-adapted to turbid waters (e.g., Porites, Pectinia, Leptastrea,
Montipora). Light extinction coefficient (K) and % live coral cover (%LCC) showed
a strong and inverse curvilinear relationship (%LCC=13.60 *K(-3.40)). Similarly,
the rate of sediment deposition (DFSPM) (RR=1.51-0.17 *DFSPM) and water clarity
(RR=3.56-2.92 *K) exhibited strong and inverse relationships with recruitment
rates (RR). Although measured levels of the downward flux of suspended
particulate matter and suspended solids were well within "normal" levels recorded
in the literature, it was the proportion of benthic space, generic coral
composition, and site history that offered compelling evidence of chronic
exposure to increased sediment load. Clearly a reduction in both water clarity
and live-coral cover has taken place since monitoring efforts began in the early
1970s, in fact coral cover has more than halved at all sites examined since the
1980s and benthic space was predominantly occupied by dead corals covered with
sediment and filamentous algae.
PMID- 17027038
TI - Globally attracting attenuant versus resonant cycles in periodic compensatory
Leslie models.
AB - We use a periodically forced density-dependent compensatory Leslie model to study
the combined effects of environmental fluctuations and age-structure on pioneer
populations. In constant environments, the models have globally attracting
positive fixed points. However, with the advent of periodic forcing, the models
have globally attracting cycles. We derive conditions under which the cycle is
attenuant, resonant, and neither attenuant nor resonant. These results show that
the response of age-structured populations to environmental fluctuations is a
complex function of the compensatory mechanisms at different life-history stages,
the fertile age classes and the period of the environment.
PMID- 17027039
TI - A general bilinear model to describe growth or decline time profiles.
AB - Linear models are widely used because of their unrivaled simplicity, but they
cannot be applied for data that have a turning-or rate-change-point, even if the
data show good linearity sufficiently far from this point. To describe such
bilinear-type data, a completely generalized version of a linearized
biexponential model (LinBiExp) is proposed here to make possible smooth and fully
parametrizable transitions between two linear segments while still maintaining a
clear connection with the linear models. Applications and brief conclusions are
presented for various time profiles of biological and medical interest including
growth profiles, such as those of human stature, agricultural crops and fruits,
multicellular tumor spheroids, single fission yeast cells, or even labor
productivity, and decline profiles, such as age-effects on cognition in patients
who develop dementia and lactation yields in dairy cattle. In all these cases,
quantitative model selection criteria such as the Akaike and the Schwartz
Bayesian information criteria indicated the superiority of the bilinear model
compared to adequate less parametrized alternatives such as linear, parabolic,
exponential, or classical growth (e.g., logistic, Gompertz, Weibull, and
Richards) models. LinBiExp provides a versatile and useful five-parameter
bilinear functional form that is convenient to implement, is suitable for full
optimization, and uses intuitive and easily interpretable parameters.
PMID- 17027040
TI - Intracellular delay limits cyclic changes in gene expression.
AB - Based on previously published experimental observations and mathematical models
for Hes1, p53 and NF-kappaB gene expression, we improve these models through a
distributed delay formulation of the time lag between transcription factor
binding and mRNA production. This description of natural variability for delays
introduces a transition from a stable steady state to limit cycle oscillations
and then a second transition back to a stable steady state which has not been
observed in previously published models. We demonstrate our approach for two
models. The first model describes Hes1 autorepression with equations for Hes1
mRNA production and Hes1 protein translation. The second model describes Hes1
repression by the protein complex Gro/TLE1/Hes1, where Gro/TLE1 is activated by
Hes1 phosphorylation. Finally, we discuss our analytical and numerical results in
relation to experimental data.
PMID- 17027042
TI - Differential noradrenergic influence on seizure expression in genetically Fast
and Slow kindling rat strains during massed trial stimulation of the amygdala.
AB - The involvement of alpha(2) noradrenergic receptors during amygdala 'massed'
stimulation (MS) was examined in rats that were selectively bred to be seizure
prone (Fast) or seizure-resistant (Slow) to amygdala kindling. The selective
alpha(2) noradrenergic agonist guanfacine, or the antagonist idazoxan, was
intraperitoneally injected during the MS procedure to study subsequent changes in
afterdischarge (AD) threshold, AD duration and behavioral seizure expression.
These measurements were again assessed weekly for 2 weeks after the MS treatment.
Daily kindling began immediately thereafter. Following 6 stage-5 once daily
convulsive seizures, guanfacine or idazoxan were re-administered. With idazoxan,
the Slow rats expressed greater numbers of convulsive seizures and longer AD
durations compared to guanfacine or saline controls during MS treatment. This pro
convulsive property of idazoxan was absent in Fast rats. By contrast, Fast rats
showed enhanced convulsive expression in the presence of guanfacine. In the fully
kindled rat, idazoxan and guanfacine differentially impacted seizure duration and
severity in the Slow rats, but again not in the Fast rats. These data suggest
that some aspect(s) of the alpha(2) noradrenergic system in the Fast and Slow
rats are dissimilar and the mechanisms by which these receptors govern seizure
genesis and propagation may be genetically controlled and distinct.
PMID- 17027041
TI - Neutrophil-activating activity and platelet-activating factor synthesis in
cytokine-stimulated endothelial cells: reduced activity in growth-arrested cells.
AB - The reactivity of endothelial cells (ECs) to proinflammatory cytokines is
critically important for the pathogenesis of vascular diseases. Here, we studied
functional alterations of human ECs during culture under a confluent condition;
i.e., the alterations of neutrophil-activating activity, platelet-activating
factor (PAF) synthesis, and granulocyte-macrophage colony-stimulating factor (GM
CSF) production in cytokine-stimulated ECs. Human umbilical vein-derived ECs
exhibited the increased activity in neutrophil activation, PAF synthesis, and GM
CSF production when stimulated by proinflammatory cytokines such as interleukin-1
beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). The activity of
cytokine-stimulated ECs to stimulate superoxide release in human neutrophils and
to produce PAF declined markedly in parallel as ECs became growth-arrested during
culture under a confluent condition. By contrast, GM-CSF production induced by
cytokine stimulation was modestly increased, and up-regulation of intercellular
adhesion molecule-1 (ICAM-1) and activation of mitogen-activated protein kinases
were not altered. The neutrophil-activating activity of cytokine-stimulated ECs
was dependent on PAF synthesis and GM-CSF production from ECs. These findings
indicate that the reduced neutrophil-activating activity in growth-arrested ECs
may be, at least in part, ascribed to down-regulation of PAF synthesis.
PMID- 17027043
TI - Pre-synaptic histamine H3 receptors regulate glutamate, but not GABA release in
rat thalamus.
AB - We have investigated the presence of histamine H(3) receptors (H(3)Rs) on rat
thalamic isolated nerve terminals (synaptosomes) and the effect of their
activation on glutamate and GABA release. N-alpha-[methyl-(3)H]histamine ([(3)H]
NMHA) bound specifically to synaptosomal membranes with dissociation constant
(K(d)) 0.78+/-0.20 nM and maximum binding (B(max)) 141+/-12fmol/mg protein.
Inhibition of [(3)H]-NMHA binding by histamine and the H(3)R agonist immepip fit
better to a two-site model, whereas for the H(3)R antagonist clobenpropit the
best fit was to the one-site model. GTPgammaS (30 microM) decreased [(3)H]-NMHA
binding by 55+/-4% and made the histamine inhibition fit better to the one-site
model. Immepip (30 nM) induced a modest, but significant increase (113+/-2% of
basal) in [(35)S]-GTPgammaS binding to synaptosomal membranes, an effect
prevented by clobenpropit (1 microM) and by pre-treatment with pertussis toxin.
In thalamus synaptosomes depolarisation-induced, Ca(2+)-dependent glutamate
release was inhibited by histamine (1 microM, 25+/-4% inhibition) and immepip (30
nM, 38+/-5% reduction). These effects were reversed by clobenpropit (1microM).
Conversely, immepip (up to 1 microM) had no effect on depolarisation-evoked
[(3)H]-GABA release. Extracellular synaptic responses were recorded in the
thalamus ventrobasal complex by stimulating corticothalamic afferents. H(3)R
activation reduced by 38+/-7% the glutamate receptor-mediated field potentials
(FPs), but increased the FP2/FP1 ratio (from 0.86+/-0.03 to 1.38+/-0.05) in a
paired-pulse paradigm. Taken together, our results confirm the presence of H(3)Rs
on thalamic nerve terminals and show that their activation modulates pre
synaptically glutamatergic, but not GABAergic neurotransmission.
PMID- 17027044
TI - Anticonvulsive effects of carbenoxolone on penicillin-induced epileptiform
activity: an in vivo study.
AB - Epilepsy is an important problem in neurological disorders. Recent studies
claimed that gap junctions have a critical role in epileptic neuronal events. The
aim of present study is to investigate the effects of gap junction blocker
carbenoxolone on penicillin-induced experimental epilepsy. For this purpose, 4
month-old male Wistar rats were used in the present study. Permanent screw
electrodes allowing EEG monitoring from conscious animals and permanent cannula
providing the administration of the substances to the brain ventricle were placed
into the cranium of rats under general anesthesia. At the end of the
postoperative recovery period, epileptiform activity was generated by injecting
300 IU crystallized penicillin through the ventricular cannula. Epileptiform
activity monitored from a digital recording system, when it reached its maximum
intensity, carbenoxolone (100, 200, 500 nmol) was applied in the same way with
penicillin. Effects of carbenoxolone on epileptiform activity were assessed by
both electrophysiological and behavioral analysis. Carbenoxolone suppressed
epileptiform activity by decreasing the amplitude and frequency of epileptiform
spikes and by attenuating the epileptiform behavior. The results of this study
suggest that the blockade of electrical synapses may contribute to the prevention
and amelioration of epileptic activity.
PMID- 17027045
TI - The effect of L-stepholidine, a novel extract of Chinese herb, on the
acquisition, expression, maintenance, and re-acquisition of morphine conditioned
place preference in rats.
AB - The effect of L-stepholidine (SPD), a novel alkaloid extract of the Chinese herb
Stephania with partial dopamine D1 receptor agonistic and D2 receptor
antagonistic dual actions, on morphine conditioned place preference (CPP) was
studied. Daily injection of morphine (10 mg/kg, i.p.) for 6 days induced CPP in
rats, and daily treatment with SPD at 10 or 20 mg/kg before morphine injection
dose-dependently attenuated morphine-induced CPP. On the day following
acquisition of morphine CPP, a single administration of SPD at 10 or 20 mg/kg
failed to block the expression of CPP. However, daily administration of SPD at 20
mg/kg for 7 days attenuated the maintenance of CPP. Morphine-induced CPP
extinguished after a 21-day saline training and then a single injection of
morphine (3 mg/kg, i.p.) induced re-acquisition of morphine CPP; however,
pretreatment with SPD at 10 or 20 mg/kg 30 min before morphine injection dose
dependently blocked morphine (3 mg/kg, i.p.)-induced re-acquisition of morphine
CPP. Furthermore, our data indicate that SPD had no effect on food-induced CPP or
state-dependent learning, suggesting that the observed effect of SPD does not
result from an inhibition of general learning ability. These results demonstrate
that SPD can inhibit acquisition, maintenance, and re-acquisition of morphine
conditioned place preference and suggest its potential for treatment of opioid
addiction.
PMID- 17027046
TI - Evidence for adenosine- and serotonin-mediated antihyperalgesic effects of
cizolirtine in rats suffering from diabetic neuropathy.
AB - Cizolirtine is a novel non-opioid drug which demonstrated antinociceptive
activity in numerous pain models in rodents. Yet, its mechanism of action remains
unknown. Several lines of evidence support the idea that adenosine (ADO) and
serotonin (5-HT) modulate nociceptive signaling. Our study aimed at investigating
whether these neuroactive molecules could be implicated in the mechanism of
action of cizolirtine. Cizolirtine-induced antihyperalgesia was compared before
and after pretreatment with ADO A(1)-A(2A) and 5-HT(1B/1D) receptor ligands in
rats rendered diabetic by streptozotocin pretreatment and suffering from
neuropathic pain. Cizolirtine alone (30-80 mg/kg, i.p.) significantly increased
mechanical nociceptive thresholds. Acute pretreatment with the A(1)-A(2A)
receptor antagonist caffeine (5 mg/kg, i.p.) or the 5-HT(1B/1D) receptor
antagonist GR-127,935 (3 mg/kg, i.p.) significantly reduced the antihyperalgesic
effects of cizolirtine. Conversely, cizolirtine-induced antihyperalgesia was
promoted by pretreatment with either the selective A(1) receptor agonist CPA (0.3
mg/kg, i.p.) or the selective 5-HT(1B) receptor agonist CP-94,253 (3mg/kg, i.p.),
and this potentiation was totally prevented by acute pretreatment with respective
antagonists. Interestingly, A(1) receptor blockade by DPCPX inhibited the
promoting effect of CP-94,253 on cizolirtine-induced antihyperalgesia, suggesting
that the adenosine A(1)-mediated step takes place downstream the serotonin 5
HT(1B)-mediated step in the neurobiological mechanisms underlying cizolirtine
action.
PMID- 17027047
TI - ATP depletion does not account for apoptosis induced by inhibition of
mitochondrial electron transport chain in human dopaminergic cells.
AB - As the mitochondrial electron transport chain (ETC) is necessary for life, its
inhibition results in cell death. To date, ETC complex (I-IV) inhibitors (ETCIs)
have been thought to induce ATP depletion, triggering cellular apoptosis. To
clarify whether the depletion of intracellular ATP is relevant to apoptosis
induced by ETCIs, we conducted comparative studies using oxidative
phosphorylation inhibitors (OPIs), including a specific F(0)F(1)ATP synthase
inhibitor oligomycin, an ionophore valinomycin and an uncoupler 2,4
dinitrophenol, as tools to deplete only ATP without influencing the ETC. In human
dopaminergic SH-SY5Y cells, ETCIs (rotenone, thenoyltrifluoroacetone, antimycin A
and potassium cyanide) depleted ATP and induced apoptosis. However, OPIs failed
to induce apoptosis despite ATP being decreased to an extent comparable to that
observed with ETCIs. Reactive oxygen species (ROS) production was augmented by
ETCIs, but not by OPIs. Furthermore, ETCI-induced apoptosis was inhibited by the
addition of an antioxidant N-acetylcysteine. Apoptosis was induced without ATP
depletion by H(2)O(2) at a concentration that generated ROS at an amount
comparable to that induced by ETCIs. Our findings demonstrate that ROS production
is more relevant than ATP depletion to apoptosis induced by ETCIs.
PMID- 17027048
TI - The "hidden" semantic category dissociation in mild-moderate Alzheimer's disease
patients.
AB - In patients manifesting mild-moderate Alzheimer's disease (AD), lexical semantic
tasks are known to be influenced by several variables which should be adequately
taken into account when studying semantic category dissociations. The following
study provides indexes of three new variables (imageability (I), percentage of
name agreement (pNA) and number of target alternatives (nTA)) and investigates
their role in naming in a group of people with AD and in matched older adults
controls. Forty young healthy participants rated I, pNA and nTA of 155 stimuli
(including living and non-living items) from and sets. Forty-eight people with
mild-moderate AD and 40 older adults were given the two naming tests and their
naming ratings were analysed with a two-way ANOVA (two groupsxtwo categories) to
assess category specificity and the effect of interaction. The influence of
relevant concomitant variables in naming was measured using a multiple regression
analysis. Semi-partial correlations were carried out to assess the independent
contribution of each variable to naming. We found that living items were more
imageable and had fewer lexical alternatives and higher name agreement than non
living items. We also found that controls significantly named better than AD
patients (F=37.551, p<.001), whilst the two-way ANOVA showed no significant
effect of category (F=.649, p=.423). Notably category effect emerged when
assessing its independent contribution performing a semi-partial correlation
(beta=-.278, p<.001) which kept the effect of relevant concomitant variables
under control. Our results confirm that category dissociation does emerge in mild
moderate AD patients when the effect of relevant concomitant variables is
adequately taken into account. The hypothesis that the highly correlated
properties of items from biological categories may play a protective effect on
living things, making them less prone to impairment in the early stages of AD, is
discussed.
PMID- 17027049
TI - Stimulus animal characteristics do not modulate the expression of partner
preference by female rats.
AB - The stimulus animals used in tests of partner preference in female rats vary. To
test the hypothesis that the alternative stimulus animal modulates the preference
for an intact male, gonadectomized (GDX) female rats received estradiol benzoate
plus progesterone or the oil vehicle and were tested for partner preference with
either an intact male paired with a GDX hormone-primed female or an intact male
paired with a GDX male. Rats were tested under conditions that limited physical
contact (No Contact) or allowed sexual interaction (Contact). Stimulus animal
condition was not a primary determinant of partner preference. In contrast,
contact condition and hormone treatment modulated preference, as well as activity
levels and the display of proceptive behaviors. Our findings demonstrate that the
characteristics of the alternative stimulus animals tested here do not play a
significant role in modulating partner preference in female rats.
PMID- 17027050
TI - Heat and social rank impact behavior and physiology of PRRS-virus-infected pigs.
AB - Changes in thermal environment can invoke a stress response in pigs, which in
turn can potentially impact their immune system and disease susceptibility. We
investigated effects of heat stress and social rank on behavior, immune
responsiveness, and performance of pigs challenged with porcine reproductive and
respiratory syndrome (PRRS) virus. Sixty-four 7-week-old PRRS-naive pigs were
assigned to each of four experimental treatments consisting of a 2 x 2 factorial
design: PRRS (PRRS- or PRRS+) and environmental temperature (24 degrees C or 32
degrees C). Blood samples were taken prior to and at days 7 and 14 post
inoculation, and alveolar macrophages were collected via bronchoalveolar lavage
at day 14. Total white blood cell counts, natural killer cytotoxicity, macrophage
numbers, macrophage subpopulations, and performance measures were all
significantly affected by social rank, heat stress, and/or infection status of
the pig. Heat stress and PRRS status also significantly influenced the amount of
time pigs spent lying with or without contacting another animal. Cortisol and
various immune measures were also affected by PRRS status. These results show not
only that intranasal inoculation with PRRS virus affects physiological,
behavioral, and performance measures in growing pigs, but that social rank
influences pigs' immune responsiveness to PRRS as well. Moreover, heat stress
does not have additive negative impact on physiological or performance traits in
pigs challenged with PRRS virus.
PMID- 17027051
TI - Are we getting what we pay for?
AB - The British NHS delivers health care free at the point of access to whomever
needs it. It is often claimed to be the envy of the world. But does it deliver
health? Or could the resource put into the health service be better spent
elsewhere? In this article, we discuss the determinants of health in the United
Kingdom in the past, the rise of public health and the impact medical technology
has had on health. We discuss resource distribution in health care, and apply the
principles of health economics to the wider context of the delivery of health,
rather than health care. With a background of rising demand for health care and
rationing of resources in the UK, combined with inequalities in life expectancy
related to position in society, we conclude that wealth redistribution,
environmental regulation, improved nutrition and better education must come first
in the priorities for achieving a healthy population.
PMID- 17027052
TI - The contribution of health to the economy in the European Union.
AB - Despite increasing recognition of the link between health and economic
development in low-income countries, the relationship has to date received scant
attention in rich countries. We argue that this lack of attention is not
justifiable. While the economic argument for investing in health in rich
countries may differ in detail from that in low-income countries, there is
considerable and convincing evidence that significant economic benefits can be
achieved by improving health not only in poor, but also in rich countries. Better
health increases labour supply and productivity and historically, health has been
a major contributor to economic growth. In spite of remaining evidence gaps
economic policy-makers also in developed countries should consider investing in
health as one (of few) ways by which to achieve their economic objectives.
PMID- 17027053
TI - When the boat comes in.
PMID- 17027054
TI - Age-related changes in hookworm infection, anaemia and iron deficiency in an area
of high Necator americanus hookworm transmission in south-eastern Brazil.
AB - Surprisingly few detailed age-stratified data exist on the epidemiology of
hookworm and iron status, especially in Latin America. We present data from a
cross-sectional survey examining 1332 individuals aged 0-86 years from a
community in south-east Brazil for hookworm, anaemia and iron deficiency. Sixty
eight percent of individuals were infected with the human hookworm Necator
americanus. The force of infection (lambda=0.354) was similar to estimates from
other areas of high hookworm transmission. Individuals from poorer households had
significantly higher prevalence and intensity of infection than individuals from
better-off households. The prevalence of anaemia, iron deficiency and iron
deficiency anaemia was 11.8%, 12.7% and 4.3%, respectively. Anaemia was most
prevalent among young children and the elderly. Univariate analysis showed that
haemoglobin and serum ferritin were both significantly negatively associated with
hookworm intensity among both school-aged children and adults. Multivariate
analysis showed that, after controlling for socio-economic status, iron
indicators were significantly associated with heavy hookworm infection. Our
results indicate that, even in areas where there is a low overall prevalence of
anaemia, hookworm can still have an important impact on host iron status,
especially in school-aged children and the elderly.
PMID- 17027055
TI - Estrogenic activity of UV filter mixtures.
AB - UV-absorbing chemicals (UV filters) are widely used for protection against UV
radiation in sunscreens and in a variety of cosmetic products and materials.
Depending on the breadth and factor of UV protection, they are added as single
compounds or as a combination thereof. Some UV filters have estrogenic activity,
but their activity and interactions in mixtures are largely unknown. In this
work, we analyzed 8 commonly used UV filters, which are pure or partial hERalpha
agonists, for their estrogenic activity in equieffective mixtures in a
recombinant yeast assay carrying the human estrogen receptor alpha (hERalpha).
Mixtures of two, four and eight UV filters alone, or in combination with 17 beta
estradiol (E2), were assessed at different effect levels and no-observed-effect
concentrations (NOEC). Predictions of the joint effects of these mixtures were
calculated by employing the concentration addition (CA) and independent action
(IA) model. Most binary mixtures comprising of pure hERalpha agonists showed a
synergistic activity at all mixture combinations. Only in combination with
benzophenone-1, antagonistic activity was observed at some effect levels. All
mixtures of four or eight, pure or pure and partial hERalpha agonists, alone or
including E2, showed synergistic activity at concentrations giving an increase of
10% of basal activity (BC10). This occurred even at concentrations that were at
the NOEC level of each single compound. Hence, there were substantial mixture
effects even though each UV filter was present at its NOEC level. These results
show that significant interactions occur in UV filter mixtures, which is
important for the hazard and risk assessments of these personal care products.
PMID- 17027056
TI - Mutagenesis of the La Crosse Virus glycoprotein supports a role for Gc (1066
1087) as the fusion peptide.
AB - The La Crosse Virus (LACV) M segment encodes two glycoproteins (Gn and Gc), and
plays a critical role in the neuropathogenesis of LACV infection as the primary
determinant of neuroinvasion. A recent study from our group demonstrated that the
region comprising the membrane proximal two-thirds of Gc, amino acids 860-1442,
is critical in mediating LACV fusion and entry. Furthermore, computational
analysis identified structural similarities between a portion of this region,
amino acids 970-1350, and the E1 fusion protein of two alphaviruses: Sindbis
virus and Semliki Forrest virus (SFV). Within the region 970-1350, a 22-amino
acid hydrophobic segment (1066-1087) is predicted to correlate structurally with
the fusion peptides of class II fusion proteins. We performed site-directed
mutagenesis of key amino acids in this 22-amino acid segment and determined the
functional consequences of these mutations on fusion and entry. Several mutations
within this hydrophobic domain affected glycoprotein expression to some extent,
but all mutations either shifted the pH threshold of fusion below that of the
wild-type protein, reduced fusion efficiency, or abrogated cell-to-cell fusion
and pseudotype entry altogether. These results, coupled with the aforementioned
computational modeling, suggest that the LACV Gc functions as a class II fusion
protein and support a role for the region Gc 1066-1087 as a fusion peptide.
PMID- 17027057
TI - Impact of genetic changes to the CRPV genome and their application to the study
of pathogenesis in vivo.
AB - The cottontail rabbit papillomavirus (CRPV)/rabbit model has been used to study
oncogenicity and immunogenicity of different antigens from the papillomavirus
genome and has therefore served as a preclinical model for the development of
preventive and therapeutic vaccines against papillomavirus infections. One unique
property of the CRPV model is that infection can be initiated using viral DNA.
This property allows for the functional testing of viral mutants in vivo. We have
introduced point mutations, insertions and deletions into all of the different
coding and non-coding regions of the CRPV genome and have tested their
infectivity in this model. We found that the majority of the mutant genomes
retained viability and could induce papillomas in domestic rabbits. These data
indicated that the CRPV genome is tolerant of many modifications without
compromising its ability to initiate skin papillomas. In combination with our
recently established HLA-A2.1 transgenic rabbit model, this plasticity allows us
to extend the utility of the CRPV/rabbit model to the screening of HLA-A2.1
restricted epitopes from other human viral and tumor antigens.
PMID- 17027059
TI - Intracellular localization of varicella-zoster virus ORF39 protein and its
functional relationship to glycoprotein K.
AB - Varicella-zoster virus (VZV) encodes two multiply inserted membrane proteins,
open reading frame (ORF) 39 protein (ORF39p) and glycoprotein K (gK). The HSV-1
homologs of these proteins are believed to act in conjunction with each other
during viral egress and cell-cell fusion, and they directly influence each
other's intracellular trafficking. However, ORF39p and VZV gK have received very
limited study largely due to difficulties in producing antibodies to these highly
hydrophobic proteins. To overcome this obstacle, we introduced epitope tags into
both ORF39p and gK and examined their intracellular distributions in transfected
and infected cells. Our data demonstrate that both ORF39p and gK accumulate
predominately in the ER of cultured cells when expressed in the absence of other
VZV proteins or when coexpressed in isolation from other VZV proteins. Therefore,
the transport of VZV ORF39p and gK does not exhibit the functional
interdependence seen in their HSV-1 homologs. However, during infection, the
primary distributions of ORF39p and gK shift from the ER to the Golgi, and they
are also found in the plasma membrane indicating that their intracellular
trafficking during infection depends on other VZV-encoded proteins. During
infection, ORF39p and gK tightly colocalize with VZV envelope glycoproteins B, E
and H; however, the coexpression of ORF39p or gK with other individual viral
glycoproteins is insufficient to alter the transport of either ORF39p or gK.
PMID- 17027058
TI - Sequence and annotation of the 369-kb NY-2A and the 345-kb AR158 viruses that
infect Chlorella NC64A.
AB - Viruses NY-2A and AR158, members of the family Phycodnaviridae, genus
Chlorovirus, infect the fresh water, unicellular, eukaryotic, chlorella-like
green alga, Chlorella NC64A. The 368,683-bp genome of NY-2A and the 344,690-bp
genome of AR158 are the two largest chlorella virus genomes sequenced to date; NY
2A contains 404 putative protein-encoding and 7 tRNA-encoding genes and AR158
contains 360 putative protein-encoding and 6 tRNA-encoding genes. The protein
encoding genes are almost evenly distributed on both strands, and intergenic
space is minimal. Two of the NY-2A genes encode inteins, the large subunit of
ribonucleotide reductase and a superfamily II helicase. These are the first
inteins to be detected in the chlorella viruses. Approximately 40% of the viral
gene products resemble entries in the public databases, including some that are
unexpected for a virus. These include GDP-d-mannose dehydratase, fucose synthase,
aspartate transcarbamylase, Ca(++) transporting ATPase and ubiquitin. Comparison
of NY-2A and AR158 protein-encoding genes with the prototype chlorella virus PBCV
1 indicates that 85% of the genes are present in all three viruses.
PMID- 17027060
TI - Adenoviral infection induces a multi-faceted innate cellular immune response that
is mediated by the toll-like receptor pathway in A549 cells.
AB - Adenovirus vectors are known to induce certain genes and impact innate response
networks, but a broad understanding of this process and its mechanisms is
currently lacking. For this reason, we chose to investigate and characterize Ad
innate immunity using homogeneous, primary MEF cells replete with all the
elements of the pathogen-sensing Toll-Like Receptor (TLR) pathway. By using an
array-based approach to maximally define transcriptome changes induced upon Ad
vector infection, we discovered that Ad infection induces a potent gene and
transcription factor network response. This response is characterized by
significant changes in the expression of genes involved in focal adhesion, tight
junction, and RNA regulation, in addition to TLR pathway and other innate sensing
genes. Further investigation using human A549 cells knocked down for various TLR
pathway adaptors, revealed significant impacts on the Ad initiation of NF-kB and
interferon responses, thus confirming TLR involvement in Ad-mediated immunity
across diverse species.
PMID- 17027061
TI - Age related differences in learning with the useful field of view.
AB - In naturalistic tasks, subjects often interact with a cluttered visual
environment in which they need to divide their attention simultaneously among
multiple objects and tasks. Previous work examining the effects of aging in tasks
that approximate these real world demands have shown that performance often
declines with age. For example, when subjects must perform central and peripheral
visual tasks simultaneously in a Useful Field of View (UFOV) task, performance on
the peripheral task declines relative to when subjects perform the peripheral
task alone, and this divided-attention deficit grows decade-by-decade throughout
our lifetimes [e.g., Sekuler, A.B., Bennett, P.J., and Mamelak, M. (2000).
Effects of Aging on the Useful Field of View. Experimental Aging Research, 26,
103-120]. Here, we investigated the extent to which age-related differences in
divided-attention could be overcome with practice. In addition, we assessed how
divided attention costs varied when initial performance levels were equated
across age groups at the start of practice. Experiment 1 determined the stimulus
durations that approximately equated attentional costs for younger and older
subjects. These stimulus durations were used in Experiments 2 and 3 to equate
task difficulty across age. Experiments 2 and 3 examined the effect of practice
for 1-2 weeks. Practice improved performance for both younger and older subjects,
and, when older subjects were provided with enough practice, their attentional
costs were equivalent to those of younger subjects. Indeed, with enough practice,
both younger and older subjects reached a point where they showed no divided
attention deficits, although older subjects may need more practice to reach this
point. Finally, the beneficial effects of practice were maintained for at least
three months.
PMID- 17027062
TI - Contamination levels of selected organochlorine and organophosphate pesticides in
the Selangor River, Malaysia between 2002 and 2003.
AB - In Malaysia, rivers are the main source of public water supplies. This study was
conducted from 2002 to 2003 to determine the levels of selected organochlorine
and organophosphate pesticides in the Selangor River in Malaysia. Surface water
samples have been collected seasonally from nine sites along the river. A liquid
liquid extraction followed by gas chromatography-mass spectrometry technique was
used to determine the trace levels of these pesticide residues. The
organochlorine pesticides detected were lindane, heptachlor, endosulfan,
dieldrin, endosulfan sulfate, o,p'-DDT, p,p'-DDT, o,p'-DDE and p,p'-DDE whereas
for organophosphate pesticides, they were chlorpyrifos and diazinon. At the river
upstream where a dam is located for public water supply, incidents of pesticide
levels exceeding the European Economic Community Directive of water quality
standards have occurred. Furthermore, the wetland ecosystems located at the
downstream of the river which houses the fireflies community is being threatened
by occasional pesticide levels above EPA limits for freshwater aquatic organisms.
The occurrence of these residual pesticides in the Selangor River can be
attributed to the intense agriculture and urban activity.
PMID- 17027063
TI - Langerhans cell histiocytosis and its relationship with Epstein-Barr virus.
PMID- 17027064
TI - Biogenic emissions of isoprenoids and NO in China and comparison to anthropogenic
emissions.
AB - In this study, a regional dynamical model (WRF) is used to drive biogenic
emission models to calculate high resolution (10x10 km) biogenic emissions of
isoprene (C(5)H(8)), monoterpenes (C(10)H(16)), and nitric oxide (NO) in China.
This high resolution biogenic inventory will be available for the community to
study the effect of biogenic emissions on photochemical oxidants in China. The
biogenic emissions are compared to anthropogenic emissions to gain insight on the
potential impact of the biogenic emissions on tropospheric chemistry, especially
ozone production in this region. The results show that the biogenic emissions in
China exhibit strongly diurnal, seasonal, and spatial variations. The isoprenoid
(including both isoprene and monoterpenes) emissions are closely correlated to
tree density and strongly vary with season and local time. During winter
(January), the biogenic isoprenoid emissions are the lowest, resulting from lower
temperature and solar radiation, and highest in summer (July) due to higher
temperature and solar radiation. The biogenic NO emissions are also higher during
summer and lower during winter, but the magnitude of the seasonal variation is
smaller than the emissions of isoprene and monoterpenes. The biogenic emissions
of NO are widely spread out in the northern, eastern, and southern China regions,
where high-density agricultural soil lands are located. Both biogenic NO and
isoprenoid emissions are very small in western China. The calculated total
biogenic emission budget is smaller than the total anthropogenic VOC emission
budget in China. The biogenic isoprenoid and anthropogenic VOC emissions are 10.9
and 15.1 Tg year(-1), respectively. The total biogenic and anthropogenic
emissions of NO are 5.9 and 11.5 Tg(NO) year(-1), respectively. The study shows
that in central eastern China, the estimated biogenic emissions of isoprenoids
are very small, and the anthropogenic emissions of VOCs are dominant in this
region. However, in northeastern and southern China, there are relatively large
biogenic emissions of isoprenoids, leading to an important impact on the ozone
production in these regions. Furthermore, the emissions of isoprenoids are
highest during summer and noontime, which correlates to the peak of ozone
production period. For example, the ratio between summer and winter for the
emissions of isoprenoids is about 15 in China. As a result, the biogenic
emissions of isoprenoids are significantly larger than the anthropogenic
emissions of VOCs in China during daytime in summer. Biogenic NO emissions are
mostly produced by agricultural soils which co-exist with large populations and
human activity. As a result, the biogenic emissions of NO are mostly overlapped
with the anthropogenic emissions of NO, leading to the enhancement in NO
concentrations in the high anthropogenic NO emission regions. Finally, the future
emissions of isoprene and monoterpenes over China are estimated. The results show
that the future biogenic emissions may increase significantly due to land cover
changes in central eastern China, which could have a very important impact on
ozone formation in this region. However, these estimates are highly uncertain and
are presented as a potential scenario to show the importance of possible changes
of biogenic emissions in China.
PMID- 17027065
TI - EPCR gene A3 haplotype and elevated soluble endothelial protein C receptor
(sEPCR) levels in Turkish pediatric stroke patients.
AB - INTRODUCTION: High plasma levels of sEPCR lead to dysfunction of the EPCR
mediated coagulation. We have evaluated the role of EPCR A3 haplotype with its
representative promoter variant 1651 C-G in a total of twenty-seven pediatric
stroke patients and fifty-nine healthy subjects. MATERIALS AND METHODS:
Genotyping of the A3 haplotype was performed with RFLP analysis. Plasma sEPCR
levels were measured with ELISA. The mutant 1651 G allele frequency was observed
to be 0.166 in the patient group. Common risk factors such as FV 1691 G-A and PT
20210 G-A mutations were also screened. RESULTS AND CONCLUSIONS: None of the
patients with sEPCR levels below 100 ng/ml carried the A3 haplotype, while
patients with elevated sEPCR levels carried the A3 haplotype either in a
heterozygous or homozygous state. Our study confirms that there is a strong
association between A3 haplotype and elevated sEPCR levels. We suggest that
elevated sEPCR levels might increase the risk of stroke at pediatric age when
compared to controls. Studies with large series of patients are warranted to
confirm this hypothesis.
PMID- 17027066
TI - Promise and problems of translational research.
PMID- 17027067
TI - The treatment of lateral T1 and T2 squamous cell carcinomas of the vulva confined
to the labium majus or minus.
AB - OBJECTIVE: To determine the pattern of lymph node metastases, recurrence rate,
and survival of patients with lateral T1 and T2 squamous cell cancer (SCC) of the
vulva treated by radical vulvectomy or hemivulvectomy and inguinal
lymphadenectomy. METHODS: An institutional review was performed to identify
lateral T1 and T2 SCC of the vulva confined to the labium majus and minus.
RESULTS: Sixty-one patients with lateral T1 and 61 patients with lateral T2 SCC
of the vulva were treated from 1963 to 2003. Radical vulvectomy (RV) was
performed in 60 patients, and radical hemivulvectomy (RHV) in 62 patients. Seven
of 61 patients (11%) with T1 lesions had ipsilateral superficial inguinal lymph
node (SIL) metastases, but none had deep inguinal lymph (DIL) node metastases.
Nineteen of 61 patients (31%) with T2 lesions had ipsilateral SIL metastases, and
8 had ipsilateral DIL metastases. No patient had contralateral SIL or DIL
metastases. Six patients (10%) with T1 lesions and seven patients (11%) with T2
lesions developed recurrence to the ipsilateral vulva and were treated by re
excision. All patients are alive with no evidence of disease 10-195 months after
treatment. One patient with T1 and three patients with T2 SCC developed distant
recurrence and died of disease (DOD) 10-15 months after surgery. Disease-free
survival of patients with T1 lesions was 98% at 2 years and 98% at 5 years, and
with T2 lesions was 95% at 2 years and 93% at 5 years. Local or distant
recurrence was not more common in patients treated by RHV than in those treated
by RV. CONCLUSION: Lateral T1 and T2 squamous cell cancers of the vulva spread to
the ipsilateral inguinal lymph nodes and can be treated effectively with RHV and
ipsilateral SIL dissection. Deep inguinal lymphadenectomy is indicated only when
the SIL are positive.
PMID- 17027068
TI - Summary and discussion of session recommendations.
PMID- 17027069
TI - Biomarkers and clinical trial design.
PMID- 17027070
TI - Potential predictors of chemotherapy response in ovarian cancer--how do we define
chemosensitivity?
AB - OBJECTIVE: The aim of this study was to assess whether microvessel density
(measured by CD31), vascular endothelial growth factor (VEGF) or multidrug
resistance (MDR1) could determine the response to chemotherapy or act as
prognostic factors in ovarian cancer. METHODS: Seventy-nine ovarian specimens
were immunostained. Pearson correlation, 1-way ANOVA and chi-square were used for
univariate analysis. Kaplan Meier survival curves were used, log-rank was used
for univariate analysis and a Cox proportional hazards regression model was used
for multivariate evaluation. Response to chemotherapy was assessed after 6 months
and again after 1 year. RESULT: Quantifying VEGF proved to be a valuable
independent prognostic indicator in progression-free survival (PFS) (p<0.05) and
overall survival (OS) (p<0.0001). VEGF correlated with response to chemotherapy
at the 6-month interval (r=0.446, p<0.001) but failed to correlate at the 1-year
interval. Increased staining with CD31 was associated with decreased PFS (p<0.01)
and OS (p<0.01) in univariate but not multivariate analysis. MDR1 failed to act
as a prognostic marker or as a predictor of response to chemotherapy. CONCLUSION:
VEGF correlates with response to chemotherapy at the 6-month but not the 12-month
interval. What should our criteria be for determining sensitivity to
chemotherapy? CD31, VEGF and MDR1 do play a role in some ovarian malignancies but
other factors are likely to be involved and perhaps molecular profiling will
determine which factors will be important for determining the response to
chemotherapy.
PMID- 17027071
TI - Expression of CD44, E-cadherin, and antimetastatic protein nm23-H1 in complete
hydatidiform moles.
AB - INTRODUCTION: There is scant information about the expression of CD44 and E
cadherin, two cell adhesion molecules, and the antimetastatic protein nm23-H1, in
complete hydatidiform moles. We measured the expression of these markers to
determine their usefulness in predicting the development of invasive disease.
MATERIALS AND METHODS: We performed a retrospective study of 27 patients with
complete hydatidiform moles, collecting clinical information including the
patient's age, pre-evacuation hCG level, pathology, hCG monitoring, and the
development of gestational trophoblastic neoplasia. Immunohistochemical staining
for CD44, E-cadherin, and nm23-H1 was performed. CD44 expression was classified
as positive or negative. For E-cadherin and nm23-H1, the intensity of expression
was graded on a 0 to 3 scale. Chi-square or Fisher's exact testing was used to
evaluate the relationship between these markers and the development of invasive
disease. RESULTS: CD44 was expressed in 26% of cases. E-cadherin expression was
1+, 2+, and 3+in 8%, 33%, and 59% of cases, respectively. Nm23-H1 expression was
1+, 2+, and 3+in 4%, 11%, and 85% of cases. The risk of developing invasive
disease did not correlate with the expression of CD44, E-cadherin, or nm23-H1.
CONCLUSION: In this preliminary study, there is no relationship between CD44, E
cadherin, and nm23-H1 expression in complete hydatidiform moles and the risk of
invasive disease. Other molecular markers predictive of invasive disease should
be sought to limit hCG surveillance to those at risk.
PMID- 17027073
TI - Intraperitoneal chemotherapy and the NCI clinical announcement.
PMID- 17027072
TI - Long-term survival from gynecologic cancer: psychosocial outcomes, supportive
care needs and positive outcomes.
AB - OBJECTIVES: To assess the long-term psychosocial outcomes and supportive care
needs of gynecologic cancer survivors. METHODS: Women who had received care in a
tertiary-based gynecologic cancer center 1-8 years earlier and who were disease
free were invited to complete a mailed self-report questionnaire to assess
psychosocial outcomes and supportive care needs. RESULTS: In total, 199 survivors
participated in the study. Survivors reported normal quality of life and
relationship adjustment although functioning was at the lower end of the range;
over two-thirds (68%) reported positive outcomes. However, nearly one-third (29%)
reported clinical levels of anxiety and the most frequently endorsed need
concerned fear of disease recurrence (24%). About one-fifth (19%) reported
symptoms that indicated posttraumatic stress disorder (PTSD) and this rose to
close to one-third (29%) for survivors of advanced stage disease. Nearly 90% of
survivors reported supportive care needs and the diagnosis of anxiety or PTSD
resulted in a four-fold increase in unmet needs. Needs most frequently concerned
"existential survivorship" (e.g., spiritual beliefs, decision making, the meaning
of life) and "comprehensive cancer care" (e.g., team care, communication, local
health care services). Years since diagnosis was not related to distress or need
levels. CONCLUSIONS: All members of the care team need to be aware that
significant psychosocial morbidity may occur many years after the successful
treatment of a gynecologic malignancy and may be associated with elevated
supportive care needs. Comprehensive and extended supportive care services are
required to address anxiety and trauma responses and investigate strategies to
meet ongoing needs in order to improve long-term psychosocial outcomes.
PMID- 17027074
TI - The future of phase II trials.
PMID- 17027075
TI - The association between exposure to environmental tobacco smoke and breast
cancer: a review by the California Environmental Protection Agency.
AB - BACKGROUND: The California Environmental Protection Agency (Cal/EPA) recently
completed a health effects assessment of exposure to environmental tobacco smoke
(ETS) which resulted in California listing ETS as a Toxic Air Contaminant in
January 2006. As part of the assessment, studies on the association between
exposure to ETS and breast cancer were reviewed. METHODS: Twenty-six published
reports (including 3 meta-analyses) evaluating the association between ETS
exposure and breast cancer were reviewed. A weight-of-evidence approach was
applied to evaluate the data and draw conclusions about the association between
breast cancer and ETS exposure. RESULTS: The published data indicate an
association between ETS and breast cancer in younger primarily premenopausal
women. Thirteen of 14 studies (10 case-control and four cohort) that allowed
analysis by menopausal status reported elevated risk estimates for breast cancer
in premenopausal women, seven of which were statistically significant. Our meta
analyses indicated elevated summary relative risks ranging from OR 1.68 (95% C.I.
1.31, 2.15) for all 14 studies to 2.20 (95% C.I. 1.69, 2.87) for those with the
best exposure assessment. CONCLUSIONS: Cal/EPA concluded that regular ETS
exposure is causally related to breast cancer diagnosed in younger, primarily
premenopausal women and that the association is not likely explained by bias or
confounding.
PMID- 17027076
TI - Involvement of Ca2+-dependent proteasome in the degradation of both cyclin B1 and
Mos during spontaneous activation of matured rat oocytes.
AB - In matured rat oocytes, spontaneous activation from the metaphase-II (MII) stage
occurred after collection from the oviducts. It is well known that the mitogen
activated protein kinase (MAPK) pathway and p34(cdc2) kinase play an important
role in the arrest at MII in other species. However, there is no information
about the difference in these factors among strains of rats. In the present
study, in spontaneously activated oocytes from the Wistar rat, the Mos protein
level and the activity of MAPK kinase (MEK)/MAPK were decreased at 120 min (13.8,
25.7, and 19.3, respectively, P<0.05), whereas Sprague-Dawley (SD) oocytes, which
were not spontaneously activated, had a high level of Mos protein and MEK/MAPK
activity (75.9, 76.2, and 87.9, respectively, P<0.05). Phosphorylation of MAPK in
the SD oocytes was significantly suppressed by MEK inhibitor, U0126 at 60 min;
this treatment decreased p34(cdc2) kinase activity via cyclin B1 degradation in a
time-dependent manner. The treatment with proteasome inhibitor, MG132 or Ca2+
chelator, BAPTA-AM, overcame the spontaneous degradation of both Mos and cyclin
B1 in a dose-dependent manner in Wistar oocytes. More than 90% of Wistar oocytes
treated with BAPTA-AM were arrested at MII until 120 min. In conclusion, SD
oocytes carrying Mos/MEK/MAPK, maintained a high activity of p34(cdc2) kinase by
stabilizing cyclin B1, thus involved in their meiotic arrest. In contrast, Wistar
oocytes had a relatively low cytostatic factor activity; rapid decrease of
Mos/MEK/MAPK failed to stabilize both cyclin B1 and Mos, and these oocytes were
likely to spontaneously activate.
PMID- 17027077
TI - Evaluation of artificial chaperoning behavior of an insoluble cyclodextrin-rich
copolymer: solid-phase assisted refolding of carbonic anhydrase.
AB - Insoluble beta-cyclodextrin (beta-CD) copolymers have been used for the refolding
of thermally and/or chemically denatured carbonic anhydrase with refolding yield
of 40% using 300 mg of the copolymer/ml refolding solution containing 0.042 mg/ml
protein. In an attempt to enhance the refolding yield with lower quantities of
the copolymer, a new beta-CD-rich copolymer with higher beta-CD content was
synthesized. Regarding the need for rapid stripping of the detergent molecules
from the detergent-protein complexes formed in the capture step of the technique
(artificial chaperone-assisted refolding), experimental variables (e.g. copolymer
and the protein contents) were optimized to improve the refolding yields along
with depressing the aggregate formation. In addition, comparative studies using
different ionic detergents and the copolymer were conducted to get a more
comprehensive understanding of the detergent's tail length in the stripping step
of the process. Our results indicated that under the optimal developed refolding
environment, the denatured CA was refolded with a yield of 75% using only 5mg of
the copolymer/1.2 ml refolding solution containing 0.0286 mg/ml protein. Taking
into account the recycling potential of the copolymer, the new resin, with
significant cost-cutting capability, is a suitable candidate for industrial
applications.
PMID- 17027078
TI - Expression and cellular localisation of chloride intracellular channel 3 in human
placenta and fetal membranes.
AB - Chloride channels regulate the movement of a major cellular anion and are
involved in fundamental processes that are critical for cell viability.
Regulation of intracellular chloride is achieved by multiple classes of channel
proteins. One class of putative channels are the chloride intracellular channel
(CLIC) family. Evidence suggests that several CLICs are expressed in human
placenta, although their roles in this tissue are not certain. Northern blot
analysis has shown that CLIC3 is highly expressed in placenta relative to other
human tissues; however, its cellular distribution is not known. This study used
microarray expression profiling to clarify which CLICs are expressed in human
placenta and RT-PCR, Western blot and immunohistochemistry to determine the
expression pattern of CLIC3 in human placenta and fetal membranes. Placentas and
fetal membranes were obtained from term pregnancies after delivery and placental
tissue was obtained from first trimester following either chorionic villous
sampling or elective pregnancy termination. Trophoblast cells were isolated from
first trimester and term placentas and placental endothelial cells were isolated
from term placentas. Microarray expression profiling identified high expression
of mRNA for CLICs 1, 3 and 4 in the isolated first trimester and term trophoblast
cells. High mRNA expression in the isolated endothelial cells was also found for
CLICs 1 and 4, but not CLIC3. Low expression was found for CLIC5 in all three
types of isolated cells. RT-PCR confirmed that CLIC3 mRNA was expressed in
trophoblast cells at both gestational ages, but was not present in endothelial
cells. CLIC3 mRNA was also identified in whole placental extracts at both
gestational ages and in term amnion and choriodecidua. Immunohistochemistry using
a chicken anti-human CLIC3 antibody localised strong CLIC3-specific staining to
the syncytiotrophoblast and villous cytotrophoblast cells in both first trimester
and term placentas, and weaker staining in extravillous trophoblast cells in
first trimester. In fetal membranes at term strong CLIC3-specific staining was
localised to chorionic trophoblast cells, with weaker staining in amniotic
epithelial and decidual cells. It was previously shown that chloride uptake was
increased into cells that had been transfected with CLIC3. CLIC3 may facilitate
chloride ion movement and the regulation of cellular processes associated with
the movement of chloride in the placental and fetal membrane cells in which it is
expressed.
PMID- 17027079
TI - Glucose transporter 1 localisation throughout pregnancy in the carnivore
placenta: light and electron microscope studies.
AB - Glucose is one of the major fetal nutrients. Maternofetal transfer requires
transport across the several placental membranes. This transfer is mediated by
one or more of the fourteen known isoforms of glucose transporter. So far only
Glucose Transporters 1 and 3 (GT1, GT3) have been shown to be located in
placental membranes. GT1 may be the only one on the syncytiotrophoblast (human)
or both may be present on the same membrane (rodents) or be required in sequence
(ruminants, horses and elephant). This paper shows GT1 to be the only transporter
demonstrable by immunocytochemistry in carnivore (cat, dog and mink)
endotheliochorial placental membranes. GT1 is invariably present on both apical
and basal surfaces of the cyto- and syncytiotrophoblast in all carnivore species
examined and the pattern of development is described from implantation to term.
PMID- 17027080
TI - Calcium microdomains and the fine control of cell function: an introduction.
PMID- 17027081
TI - Ca2+-sparks constitute elementary building blocks for global Ca2+-signals in
myocytes of retinal arterioles.
AB - Spontaneous Ca2+-events were imaged in myocytes within intact retinal arterioles
(diameter <40 microm) freshly isolated from rat eyes. Ca2+-sparks were often
observed to spread across the width of these small cells, and could summate to
produce prolonged Ca2+-oscillations and contraction. Application of cyclopiazonic
acid (20 microM) transiently increased spark frequency and oscillation amplitude,
but inhibited both sparks and oscillations within 60s. Both ryanodine (100
microM) and tetracaine (100 microM) reduced the frequency of sparks and
oscillations, while tetracaine also reduced oscillation amplitude. None of these
interventions affected spark amplitude. Nifedipine, which blocks store filling
independently of any action on L-type Ca2+-channels in these cells, reduced the
frequency and amplitude of both sparks and oscillations. Removal of external
[Ca2+] (1mM EGTA) also reduced the frequency of sparks and oscillations but these
reductions were slower in onset than those in the presence of tetracaine or
cyclopiazonic acid. Cyclopiazonic acid, nifedipine and low external [Ca2+] all
reduced SR loading, as indicated by the amplitude of caffeine evoked Ca2+
transients. This study demonstrates for the first time that spontaneous Ca2+
events in small arterioles of the eye result from activation of ryanodine
receptors in the SR and suggests that this activation is not tightly coupled to
Ca2+-influx. The data also supports a model in which Ca2+-sparks act as building
blocks for more prolonged, global Ca2+-signals.
PMID- 17027082
TI - The role of depression and dissociation in the relationship between childhood
trauma and bulimic symptoms among ethnically diverse female undergraduates.
AB - OBJECTIVE: The goals of this study were to examine the role of dissociation and
depression as possible mediators of the relationship between several forms of
childhood trauma and bulimic symptomatology and to explore potential ethnic
differences in these relationships. METHOD: Four hundred seventeen female
undergraduates participated in this cross-sectional study. They completed
measures of dissociative, depressive, and bulimic symptoms, and childhood trauma.
Experiences of multiple forms of childhood trauma were measured, including
physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional
neglect. However, only emotional abuse was correlated with bulimic symptoms at
p<.01. Therefore, other forms of trauma were excluded from the analyses to
control for Type I error. RESULTS: Dissociation was not associated with emotional
abuse after controlling for depression; therefore, tests of dissociation as a
mediator were discontinued. Depression was significantly associated with
emotional abuse after controlling for dissociation. Emotional abuse was
significantly associated with bulimia. Finally, emotional abuse and depression
together were significantly associated with bulimia after controlling for
dissociation. However, emotional abuse became nonsignificant when entered with
depression, indicating that depression mediated the relationship between
emotional abuse and bulimic symptoms. There were no ethnic differences in this
relationship. CONCLUSIONS: It appears that among women who have experienced
childhood emotional abuse, depression is more strongly associated with unhealthy
eating behaviors than is dissociation. Results also suggest that emotional abuse
is a form of childhood trauma particularly relevant to bulimia.
PMID- 17027083
TI - Modeling how CD46 deficiency predisposes to atypical hemolytic uremic syndrome.
AB - Mutations in complement regulatory proteins predispose to the development of
aHUS. Approximately 50% of patients bear a mutation in one of three complement
control proteins, factor H, factor I, or membrane cofactor protein (MCP; CD46).
Another membrane regulator that is closely related to MCP, decay accelerating
factor (DAF; CD55) thus far has shown no association with aHUS and continues to
be investigated. The goal of this study was to compare the regulatory profile of
MCP and DAF and to assess how alterations in MCP predispose to complement
dysregulation. We employed a model system of complement activation on Chinese
hamster ovary (CHO) cell transfectants. The four regularly expressed isoforms of
MCP and DAF inhibited C3b deposition by the alternative pathway. DAF, but not
MCP, inhibited the classical pathway. Most patients with MCP-aHUS are
heterozygous and express only 25-50% of the wild-type protein. We, therefore,
analyzed the effect of reduced levels of wild-type MCP and found that cells with
lowered expression levels were less efficient in inhibiting alternative pathway
activation. Further, a dysfunctional MCP mutant, expressed at normal levels and
identified in five patients with aHUS (S206P), failed to protect against C3b
amplification on CHO cells, even if expression levels were increased 10-fold. Our
results add new information relative to the necessity for appropriate expression
levels of MCP and further implicate the alternative pathway in disease processes
such as aHUS.
PMID- 17027084
TI - Distinct role of IL-3 promoter and enhancer region in murine mast cells.
AB - Crosslinking of Fcvarepsilon receptor on mast cells induces IL-3 gene expression
with the concentration dependent of intracellular calcium, but its regulatory
mechanism remains unclear. Here, we found that phorbol 12-myristate 13-acetate
(PMA) alone did not induce IL-3 gene expression, but potentiated A23187-induced
IL-3 gene expression. Interestingly, the A23187-induced IL-3 promoter activity
was suppressed by PMA, but it was enhanced when IL-3 promoter contained enhancer
region, a DH site. While IL-3 mRNA expression was increased by A23187 and PMA in
a dose-dependent manner, the promoter activity appeared all or none in all doses
of A23187 and PMA. IL-3 promoter region between -293 and -150bp was responsible
for A23187-induced gene expression and PMA- or cyclosporin A (CsA)-mediated
suppression. Taken together, IL-3 gene expression was primarily regulated at the
transcriptional level, which was differentially controlled by a restricted
promoter and enhancer region.
PMID- 17027085
TI - Structure and biological properties of the copper(II) complex with the quinolone
antibacterial drug N-propyl-norfloxacin and 2,2'-bipyridine.
AB - The neutral mononuclear copper complex with the quinolone antibacterial drug N
propyl-protected norfloxacin, Hpr-norfloxacin, in the presence of the nitrogen
donor heterocyclic ligand 2,2'-bipyridine has been prepared and characterized.
The crystal structure of (chloro)(2,2'-bipyridine)(pr-norfloxacinato)copper(II),
1, has been determined and refined with X-ray crystallography. X-band electron
paramagnetic resonance (=EPR) spectroscopy at liquid helium temperatures from
powdered samples indicates the presence of dimeric units in consistency with the
crystal structure. In aqueous solutions of 1 the EPR behavior indicates mixture
of dimeric and monomeric species. The antimicrobial activity of the complex has
been tested on three different microorganisms and the best inhibition
(MIC=0.25mugmL(-1)) has been exhibited against Escherichia coli. The study of the
interaction of the complex with calf-thymus DNA has been performed with diverse
spectroscopic techniques and has shown that complex 1 is bound to calf-thymus DNA
by the intercalative mode. Potential anticancer cytostatic and cytotoxic effects
of complex 1 on human promyelocytic leukemia HL-60 and human chronic myelogenous
leukemia K562 cell lines have been investigated. Complex 1 shows an increased
antiproliferative and necrotic effect on both HL-60 and K562 human leukemia cells
in comparison to the free pr-norfloxacin.
PMID- 17027086
TI - Microbiologically confirmed meningoencephalitis due to Enterococcus avium: a
first report.
AB - We describe an 80-year-old lady with a meningoencephalitic illness followed by
vertebral discitis. Enterococcus avium was cultured from her cerebrospinal fluid.
No other pathogen was incriminated in her illness. The meningoencephalitic
illness settled after 3 weeks of antimicrobials, but the vertebral discitis
required longer therapy.
PMID- 17027087
TI - Bipolar spectrum and drug addiction.
PMID- 17027088
TI - Integrin alpha5 is involved in fibronectin-induced human extravillous trophoblast
invasion.
AB - To identify the molecules involved in human extravillous trophoblast (EVT)
invasion, we raised murine mAbs that react with EVTs and obtained one mAb (CHL3)
that inhibited invasion of a human choriocarcinoma-derived cell line, BeWo cells.
The N-terminal 22 aminoacid sequence of the CHL3 antigen (150kDa) purified from
placental tissue completely matched that of integrin alpha5, which is known to
interact with fibronectin. Double immunohistochemical staining and flow cytometry
confirmed the reactivity of CHL3 with integrin alpha5 and its expression on the
surface of BeWo cells and human EVTs isolated from villous explant cultures. CHL3
mAb inhibited the attachment of human EVTs and BeWo cells to fibronectin-coated
dishes, but not to Matrigel dishes. In the Matrigel invasion assay supplemented
with or without fibronectin, the invasion of isolated EVTs and BeWo cells was
attenuated by treatment with CHL3 without affecting cell proliferation. During
invasion assays, the production of matrix metalloproteases 2 and 9 was not
changed by CHL3. These findings suggest that interaction with fibronectin through
integrin alpha5 plays an important role in human extravillous trophoblast
invasion.
PMID- 17027089
TI - Natural Killer T cells in patients with major depressive disorder.
AB - CD56 (Natural Killer T) cells showed a significant negative correlation with
depressive symptom scale scores in acute and unmedicated patients with major
depressive disorder. Decreased CD56 cells may reflect the severity of depressive
symptoms but not the severity of anxiety symptoms in major depression.
PMID- 17027090
TI - Expression and function of TLR2, TLR4, and Nod2 in primary canine colonic
epithelial cells.
AB - The gut maintains a delicate balance between the downregulation of inflammatory
reactions to commensal bacteria and the capacity to respond to pathogens with
vigorous cellular and humoral immune responses. Intestinal epithelial cells,
including colonic epithelial cells (CECs) possess many properties of cells of the
innate immune system, in particular the ability to recognize and respond to
microbial antigens. Recognition of microorganisms by CECs is based upon their
recognition of signature molecules, called microbe-associated molecular patterns
(MAMP), by pattern recognition receptors (PRR) including membrane toll-like
receptors (TLR) and cytosolic Nod2, an intracellular counterpart of TLRs. The
purpose of this study was to determine whether primary CECs from normal dogs
express a functional TLR2, TLR4, and Nod2 and whether they are regulated by
inflammatory mediators. We show that canine primary CECs express TLR2, TLR4, and
Nod2 that can be modulated in response to their respective MAMPs,
lipopolysaccharides (LPS) or peptidoglycans (PGN). Furthermore, we demonstrate
that these receptors are functional as evidenced by the induction of cytokine
gene expression in response to LPS or PGN.
PMID- 17027092
TI - Maternal IgG suppresses NMDA-induced spasms in infant rats and inhibits NMDA
mediated neurotoxicity in hippocampal neurons.
AB - Maternal immunoglobulin G (IgG) was derived from Wistar rats that just delivered
the new offsprings. We examined the effect of this maternal IgG on infantile
spasms induced by N-methyl-d-aspartate (NMDA) in immature rats. Pup animals were
treated subcutaneously with 10 mg/kg/day maternal IgG from day 11 to day 15 after
birth followed by a single intraperitoneal dose of NMDA (15 mg/kg).
Administration of maternal IgG decreased the severity and increased the number of
ACTH immunoreactive cells in the cortex of rats with NMDA-induced spasms.
Furthermore, maternal IgG inhibited NMDA-induced intracellular LDH activity in
cultured hippocampal neurons in a dose-dependent manner. The results indicate
that maternal IgG can attenuate NMDA-induced seizures. In infantile spasms, some
factors may during pregnancy negatively affect the transfer of maternal IgG from
mother to fetus thereby causing a decrease in the amount of protective maternal
IgG.
PMID- 17027091
TI - The immune response to disialoganglioside GD3 vaccination in normal dogs: a
melanoma surface antigen vaccine.
AB - As a result of its metastatic potential, canine malignant melanoma like its human
counterpart like its human counter part, has a poor response to conventional
treatment protocols. This prompted us to investigate the possibility of enhancing
the immune response against the melanoma cell surface antigen, disialoganglioside
GD3. Initially a flow cytometric study was designed in which the incidence of GD3
on the cell surface, recognized by the monoclonal antibody Mel-1 (R24), was
established in canine melanoma cell lines. Results from the flow cytometry found
GD3 to be highly expressed (94.2%) in six out of seven canine melanoma cell
lines. Since it was thus potentially a good target, a study in which normal dogs
were vaccinated intradermally with a vaccine containing GD3 plus adjuvants was
designed. The adjuvant included CpG oligodeoxynucleotide (CpG-ODN) sequences and
RIBI-adjuvant, which are known to target toll-like receptors (TLR) of the innate
immune system. From a cohort of 10 dogs, 4 were vaccinated 3 times, at 4 weekly
intervals with GD3 plus adjuvant, and 4 received only RIBI-adjuvant, and 2
phosphate buffered saline. Caliper measurements were collected to assess skin
reaction at the vaccination site and sera assayed for IgM and IgG antibodies
against GD3 and cell-mediated cytotoxicity against a melanoma cell line. Results
from the study found significant differences (P<0.05) in the vaccine site
reactions, IgM/IgG levels and cell-mediated cytotoxicity in the vaccinated versus
unvaccinated dogs. The addition of CpG-ODN sequences and increasing GD3
concentration in the vaccine increased the inflammation response at the injection
site. GD3 IgG and IgM antibodies in vaccinated dogs showed increasing titers over
time and achieved significance at weeks 9 and 12, respectively. Cell-mediated
cytotoxicity was only detected in peripheral blood mononuclear cells from
vaccinated dogs. In conclusion, by combining the tumor antigen GD3 (a known weak
self-antigen) and an adjuvant, tolerance was overcome by an innate and adaptive
immune response in this population of normal dogs.
PMID- 17027093
TI - Clozapine but not haloperidol treatment reverses sub-chronic phencyclidine
induced disruption of conditional discrimination performance.
AB - Abusers of phencyclidine (PCP) often present with a symptom profile similar to
that exhibited by schizophrenic patients. Animal models utilising such
psychotomimetics are currently informing research into the condition.
Accumulating evidence suggests that a central cognitive deficit in schizophrenia
is the inability to use task-setting cues to guide goal directed behaviour and
that this ability is mediated by prefrontal dopamine (DA). The current study used
the non-competitive NMDA antagonist phencyclidine (PCP) and Haloperidol (typical
antipsychotic) and Clozapine (atypical antipsychotic) in order to further
investigate the influence of DAergic manipulation on a task that requires the use
of conditional information to inform goal-directed performance. An instrumental
conditional discrimination task was employed in which rats learn to respond
appropriately according to the presence of specific auditory conditional stimuli.
Probe test 1 showed impaired conditional discrimination performance following sub
chronic PCP administration (seven twice-daily injection protocol) compared to
control which was reversed by acute treatment with clozapine (5 mg/kg) but not
haloperidol (0.1 mg/kg) both administered 60 min pre-test. Probe test 2 (8 days
post-treatment) showed enduring deficits to conditional discrimination
performance that were again reversed by clozapine but not haloperidol (injection
procedures as above). These results show that tasks dependent upon conditional
relationships are particularly sensitive to manipulation of DAergic systems as
prolonged treatment with PCP has been shown to selectively reduce prefrontal
cortex (PFC) DA activity and treatment with clozapine (known to ameliorate
cognitive deficits) but not haloperidol has been shown to selectively restore PFC
DA levels.
PMID- 17027094
TI - Neuroprotection by endogenous and exogenous PACAP following stroke.
AB - We investigated the effects of PACAP treatment, and endogenous PACAP deficiency,
on infarct volume, neurological function, and the cerebrocortical transcriptional
response in a mouse model of stroke, middle cerebral artery occlusion (MCAO).
PACAP-38 administered i.v. or i.c.v. 1 h after MCAO significantly reduced infarct
volume, and ameliorated functional motor deficits measured 24 h later in wild
type mice. Infarct volumes and neurological deficits (walking faults) were both
greater in PACAP-deficient than in wild-type mice, but treatment with PACAP
reduced lesion volume and neurological deficits in PACAP-deficient mice to the
same level of improvement as in wild-type mice. A 35,546-clone mouse cDNA
microarray was used to investigate cortical transcriptional changes associated
with cerebral ischemia in wild-type and PACAP-deficient mice, and with PACAP
treatment after MCAO in wild-type mice. 229 known (named) transcripts were
increased (228) or decreased (1) in abundance at least 50% following cerebral
ischemia in wild-type mice. 49 transcripts were significantly up-regulated only
at 1 h post-MCAO (acute response transcripts), 142 were up-regulated only at 24 h
post-MCAO (delayed response transcripts) and 37 transcripts were up-regulated at
both times (sustained response transcripts). More than half of these are
transcripts not previously reported to be altered in ischemia. A larger
percentage of genes up-regulated at 24 hr than at 1 hr required endogenous PACAP,
suggesting a more prominent role for PACAP in later response to injury than in
the initial response. This is consistent with a neuroprotective role for PACAP in
late response to injury, i.e., even when administered 1 hr or more after MCAO.
Putative injury effector transcripts regulated by PACAP include beta-actin,
midline 2, and metallothionein 1. Potential neuroprotective transcripts include
several demonstrated to be PACAP-regulated in other contexts. Prominent among
these were transcripts encoding the PACAP-regulated gene Ier3, and the
neuropeptides enkephalin, substance P (tachykinin 1), and neurotensin.
PMID- 17027095
TI - Peroxisomes and aging.
AB - Peroxisomes are indispensable for proper functioning of human cells. They
efficiently compartmentalize enzymes responsible for a number of metabolic
processes, including the absolutely essential beta-oxidation of specific fatty
acid chains. These and other oxidative reactions produce hydrogen peroxide, which
is, in most instances, immediately processed in situ to water and oxygen. The
responsible peroxidase is the heme-containing tetrameric enzyme, catalase. What
has emerged in recent years is that there are circumstances in which the tightly
regulated balance of hydrogen peroxide producing and degrading activities in
peroxisomes is upset-leading to the net production and accumulation of hydrogen
peroxide and downstream reactive oxygen species. The factor most essentially
involved is catalase, which is missorted in aging, missing or present at reduced
levels in certain disease states, and inactivated in response to exposure to
specific xenobiotics. The overall goal of this review is to summarize the
molecular events associated with the development and advancement of peroxisomal
hypocatalasemia and to describe its effects on cells. In addition, results of
recent efforts to increase levels of peroxisomal catalase and restore oxidative
balance in cells will be discussed.
PMID- 17027096
TI - Primary hyperoxaluria type 1: AGT mistargeting highlights the fundamental
differences between the peroxisomal and mitochondrial protein import pathways.
AB - Primary hyperoxaluria type 1 (PH1) is an atypical peroxisomal disorder, as befits
a deficiency of alanine:glyoxylate aminotransferase (AGT), which is itself an
atypical peroxisomal enzyme. PH1 is characterized by excessive synthesis and
excretion of the metabolic end-product oxalate and the progressive accumulation
of insoluble calcium oxalate in the kidney and urinary tract. Disease in many
patients is caused by a unique protein trafficking defect in which AGT is
mistargeted from peroxisomes to mitochondria, where it is metabolically
ineffectual, despite remaining catalytically active. Although the peroxisomal
import of human AGT is dependent upon the PTS1 import receptor PEX5p, its PTS1 is
exquisitely specific for mammalian AGT, suggesting the presence of additional
peroxisomal targeting information elsewhere in the AGT molecule. This and many
other functional peculiarities of AGT are probably a consequence of its rather
chequered evolutionary history, during which much of its time has been spent
being a mitochondrial, rather than a peroxisomal, enzyme. Analysis of the
molecular basis of AGT mistargeting in PH1 has thrown into sharp relief some of
the fundamental differences between the requirements of the peroxisomal and
mitochondrial protein import pathways, particularly the properties of peroxisomal
and mitochondrial matrix targeting sequences and the different conformational
limitations placed upon importable cargos.
PMID- 17027097
TI - The importomer--a peroxisomal membrane complex involved in protein translocation
into the peroxisome matrix.
AB - The import of proteins into the peroxisome matrix is an essential step in
peroxisome biogenesis, which is critical for normal functioning of most
eukaryotic cells. The translocation of proteins across the peroxisome membrane
and the dynamic behavior of the import receptors during the import cycle is
facilitated by several peroxisome-membrane-associated protein complexes, one of
which is called the importomer complex [B. Agne, N.M. Meindl, K. Niederhoff, H.
Einwachter, P. Rehling, A. Sickmann, H.E. Meyer, W. Girzalsky, W.H. Kunau, Pex8p:
an intraperoxisomal organizer of the peroxisomal import machinery, Mol. Cell 11
(2003) 635-646; P.P. Hazra, I. Suriapranata, W.B. Snyder, S. Subramani,
Peroxisome remnants in pex3Delta cells and the requirement of Pex3p for
interactions between the peroxisomal docking and translocation subcomplexes,
Traffic 3 (2002) 560-574. ]. We provide below a brief historical perspective
regarding the importomer and its role in peroxisome biogenesis. We also identify
areas in which further work is needed to uncover the physiological role of the
importomer.
PMID- 17027098
TI - The ether lipid-deficient mouse: tracking down plasmalogen functions.
AB - Chemical and physico-chemical properties as well as physiological functions of
major mammalian ether-linked glycerolipids, including plasmalogens were reviewed.
Their chemical structures were described and their effect on membrane fluidity
and membrane fusion discussed. The recent generation of mouse models with ether
lipid deficiency offered the possibility to study ether lipid and particularly
plasmalogen functions in vivo. Ether lipid-deficient mice revealed severe
phenotypic alterations, including arrest of spermatogenesis, development of
cataract and defects in central nervous system myelination. In several cell
culture systems lack of plasmalogens impaired intracellular cholesterol
distribution affecting plasma membrane functions and structural changes of ER and
Golgi cisternae. Based on these phenotypic anomalies that were accurately
described conclusions were drawn on putative functions of plasmalogens. These
functions were related to cell-cell or cell-extracellular matrix interactions,
formation of lipid raft microdomains and intracellular cholesterol homeostasis.
There are several human disorders, such as Zellweger syndrome, rhizomelic
chondrodysplasia punctata, Alzheimer's disease, Down syndrome, and Niemann-Pick
type C disease that are distinguished by altered tissue plasmalogen
concentrations. The role plasmalogens might play in the pathology of these
disorders is discussed.
PMID- 17027099
TI - Prospective evaluation of atrial tachyarrhythmias in patients with interatrial
block.
AB - INTRODUCTION: Interatrial block (P-wave> or =110 ms) is clinically associated
with left atrial enlargement and electromechanical dysfunction as well as atrial
tachyarrhythmias. We prospectively evaluated the incidence of such arrhythmias,
especially atrial fibrillation among patients with interatrial block over the
course of 1 year. METHODS: 118 patients (aged 48 to 104 years; female 56.6%) who
had been hospitalized between December 15, 2004 and January 14, 2005 were
identified and divided into 3 groups based on their respective baseline
electrocardiogram (interatrial block=41 patients, sinus non-interatrial block=51
patients and atrial tachyarrhythmia=24 patients). Patients were subsequently
followed for 12 months for pertinent cardiovascular events (heart failure,
peripheral embolism, transient ischemic attacks and stroke), atrial
tachyarrhythmias (atrial fibrillation and atrial flutter) and death as endpoints.
RESULTS: 19 patients (17.9%) had atrial fibrillation during the 12-month follow
up (sinus non-interatrial block group=4 [9.1%], interatrial block group=12
[29.3%] and atrial tachyarrhythmia group=3 [14.3%]). Coronary artery disease,
hypertension, pre-existing atrial fibrillation history, dilated cardiomyopathy,
atrioventricular valvular disease and interatrial block (age- and sex-adjusted
hazard ratio=4.2; 95% confidence interval 1.2-14.4; p=0.02) were significantly
associated with future events of atrial fibrillation. However, logistic
regression analysis indicated that interatrial block was not an independent
predictor of future atrial fibrillation whereas only history of pre-existing
atrial tachyarrhythmias was (hazard ratio=23.6; 95% confidence interval 4.5
121.7; p=0.0002). CONCLUSION: Interatrial block may be associated with atrial
fibrillation but in a 12-month period, does not appear to be an independent
predictor of future atrial fibrillation. Continued prospective investigation of
such a relationship is certainly warranted given its already known consequences.
PMID- 17027100
TI - Sildenafil therapy for pulmonary arterial hypertension associated with atrial
septal defects.
AB - BACKGROUND: There is increasing evidence for beneficial effects of the type 5
phosphodiesterase inhibitor, sildenafil, in idiopathic pulmonary arterial
hypertension (PAH). The effects of sildenafil in severe PAH associated with an
atrial septal defect (ASD) have not been clearly delineated. METHODS: This
extended case series reviews our experience with sildenafil treatment in three
patients with severe PAH and Eisenmenger syndrome associated with an ASD. Case
notes were reviewed for baseline and follow-up anatomic, clinical and
haemodynamic characteristics. RESULTS: Of three patients identified, median age
44.3 years (range, 28 to 59 years), two had large secundum ASDs and the other a
sinus venous defect. All patients had severe PAH and were desaturated at rest
and/or during exercise. Sildenafil was started because of progressive and severe
effort intolerance. All patients experienced symptomatic improvement, had higher
arterial saturations (range 8-19%) and improvement in effort tolerance (88 m and
56 m improvement in 6-min walk test distance (MWTD) in two patients). Right
ventricular (RV) function and Doppler derived RV systolic pressure improved in
two patients. Pulmonary arterial pressures decreased in two patients who had
cardiac catheterization (range 4 to 14 mm Hg). Pulmonary vascular resistance
decreased from 7.58 to 3.8 Wood's units in one patient who is now awaiting
surgery. Another patient developed significant pulmonary vasoreactivity (8.3 to
6.2 Wood's units with 100% oxygen) after 16 months of sildenafil therapy.
CONCLUSIONS: Sildenafil not only relieves symptoms associated with severe PAH in
patients with large ASDs, but also improves pulmonary arterial hemodynamics and
RV function.
PMID- 17027101
TI - Angina caused by coronary steal phenomenon.
PMID- 17027102
TI - Atrial fibrillation is associated with increased neurohumoral activation and
reduced exercise tolerance in patients with non-ischemic dilated cardiomyopathy.
AB - OBJECTIVES: To assess atrial fibrillation (AF) associated differences in
proinflammatory cytokines, natriuretic peptide levels and exercise capacity in
patients with heart failure (HF) secondary to non-ischemic dilated cardiomyopathy
(NIDC). METHODS: We studied 147 NIDC patients, mean age 58.3+/-12.5 years, left
ventricular (LV) ejection fraction 27.8+/-10.9% and NYHA class II-III.
Neurohumoral activation was assessed by measurement of interleukin IL-1, IL-6,
tumor necrosis factor-a (TNF-a), its soluble receptors sTNFR I and II, N-terminal
atrial (NT-ANP) and -brain (NT-BNP) natriuretic peptide levels, and functional
class was assessed by cardiopulmonary exercise test. RESULTS: Forty patients
(27.5%) had chronic AF and they did not differ in age, LV ejection fraction or HF
duration compared to patients in sinus rhythm (SR). AF was associated with
increased levels of IL-6 (p=0.001), TNF-a (p=0.002), sTNFRI (p=0.023), NT-ANP
(p<0.001) and NT-BNP (p=0.003), decreased exercise duration (p<0.001) and
slightly reduced maximal oxygen consumption at peak exercise (p=0.07) compared to
SR patients. No significant differences in cytokine and natriuretic peptide
levels or exercise tolerance were noted when patients in AF were compared to the
subgroup of SR with restrictive LV filling pattern. Multivariate analysis showed
that NT-ANP (p=0.003) and IL-6 (p=0.006) plasma levels were independently
associated with the presence of AF in our patient population. CONCLUSION: AF is
associated with increased inflammatory state, natriuretic peptide levels and
reduced exercise capacity in patients with HF secondary to NIDC. These findings
suggest that the presence of AF in HF represents a more advanced stage of the
syndrome.
PMID- 17027103
TI - The impact of cardiorespiratory fitness on inflammatory markers in patients with
metabolic syndrome.
PMID- 17027104
TI - Functional effects of nitric oxide-releasing aspirin on vein conduits of diabetic
patients undergoing CABG.
AB - BACKGROUND: Type 2 diabetes mellitus (DM) is known to negatively affect
biological properties of venous vasculature, and, particularly, to reduce
endothelium-derived nitric oxide release. This condition might influence venous
graft function following coronary artery bypass surgery (CABG). The aim of this
study was to evaluate the functional effects of a NO-releasing aspirin (NORA) on
vein grafts (VG) of diabetics and control patients undergoing elective CABG.
METHODS: In 40 consecutive ischemic heart disease patients, the effects of NORA
were tested on segments of saphenous vein conduits harvested during elective
CABG. Twenty patients had type-2 DM (mean age 69+/-2), whereas 20 patients had no
DM (NDM) and represented the control group (mean age 67+/-4). Functional
responses were tested by exposing VGs to NORA and to standard vasoactive agents
in an organ-bath preparation. Histological features of VGs were also assessed by
light and electronic microscopy. RESULTS: Significant impairment of endothelial
dependent vasodilation (acetylcholine induced) was documented in VGs of DM
subjects. NORA induced a significant and comparable vascular relaxation in all
venous segments of NDM and DM patients (56+/-12% of maximal relaxation vs 61+/
11% in the control group, respectively). Histology showed variable extent of
vascular layer and cellular abnormalities in VGs of diabetics (intimal
hyperplasia, calcific deposition, endothelial cell degeneration) likely
responsible of the endothelial functional impairment, whereas control group VG
showed preserved structures. CONCLUSIONS: This preliminary study confirms the
impairment of endothelium-dependent vasodilative property of VGs in DM patients.
It also indicates that NORA effectively induces vasodilation of VGs which was
effective also in DM patients thereby representing a promising therapy for
diabetics undergoing CABG with the use of VGs, although further studies are
mandatory to conclusively assess the safety and benefits of this pharmacological
agent.
PMID- 17027105
TI - The last Swan song for the Swan-Ganz catheter?
PMID- 17027106
TI - Plasma von Willebrand factor and soluble E-selectin levels in stable outpatients
with systolic heart failure: the Frederiksberg heart failure study.
AB - BACKGROUND: Endothelial dysfunction is a well-established aspect of the
pathophysiology of patients with systolic heart failure. We have previously
reported that patients who have had multiple current or previous hospital
admissions for decompensated heart failure have consistently shown abnormal
levels of plasma von Willebrand factor (vWf, an index of endothelial
damage/dysfunction) and soluble E-selectin (E-sel, an index of endothelial
activation), as well as other indices of endothelial perturbation. METHODS: To
investigate if endothelial abnormalities extend to CHF outpatients who have only
been recently diagnosed or have relatively mild or few, stable symptoms (at
baseline), given the better prognosis in these patients, we performed a cross
sectional analysis of CHF patients, where vWf and E-sel levels (as indices of
endothelial perturbation) were measured (ELISA) and related to left ventricular
ejection fraction (LVEF), exercise capacity (6-min walk test) and N-terminal pro
Brain Natiuretic Peptide (NT-proBNP). RESULTS: There were no statistically
significant differences in vWf and E-sel levels amongst patients with systolic
heart failure compared to controls. Plasma NT-proBNP levels in patients with CHF
were significantly elevated compared to controls (p<0.0001). Among the patients
with CHF, higher NT-proBNP levels correlated with poorer LVEF [Spearman r=-0.244,
p<0.004] and shorter 6-min walk distance [Spearman r=-0.226, p=0.045] but not
NYHA class. Plasma vWf or E-sel levels did not correlate with LVEF, 6-min walk
test or NYHA class. NT-proBNP levels correlated weakly with E-sel [Spearman r=
0.211, p=0.015] but not vWf. CONCLUSION: The present observation suggests that
stable CHF outpatients with few symptoms may in fact have less severe endothelial
perturbation, as reflected by plasma indices such as vWf and E-selectin. There
was limited association of endothelial indices to LVEF, exercise capacity, NYHA
class and NT-proBNP levels.
PMID- 17027107
TI - Obesity epidemic in modern China.
PMID- 17027108
TI - Evaluation of 1MDS electropositive microfilters for simultaneous recovery of
multiple microbe classes from tap water.
AB - The 1MDS electropositive microfilter was designed specifically for virus capture
and recovery from water, but its electrostatic properties raise the possibility
that 1MDS filters can also effectively capture bacteria and parasites present in
water samples. This filter is recommended by United States Environmental
Protection Agency (USEPA) for recovering human enteric viruses from water
matrices through the Virus Adsorption-Elution (VIRADEL) technique. If bacteria
and parasites can also be concentrated and recovered using 1MDS filters, this
sampling technique would have greater utility and cost-effectiveness for
microbial water quality testing. In this study, both 142-mm flat and 25.4-cm
cartridge 1MDS filters (Cuno) were tested to determine their effectiveness for
recovery of MS2 and phi X174 bacteriophage, Salmonella enterica (serovar
Typhimurium), Bacillus globigii endospores, and Cryptosporidium parvum oocysts
from a tap water matrix. By amending the USEPA standard beef extract/glycine
eluent with a surfactant (Tween 80) and dispersant (sodium polyphosphate) and
varying the pH and temperature, multiple eluent conditions were compared in order
to identify an optimum eluent for all organisms. While viruses, bacteria, and
parasites are effectively retained by the 1MDS filter, elution efficiencies and
associated recovery efficiencies varied for each organism.
PMID- 17027109
TI - The effect of task preparation in task switching as reflected on lateralized
readiness potential.
AB - The present study examined whether task preparation had an equivalent beneficial
effect for both switch and repeat trials in the context of a task switching
paradigm. A pair-wise task-switching paradigm was used where each trial was
comprised of two tasks that were either the same (task repeat) or different (task
switch). The effect of preparation was manipulated so that participants either
performed pure repeat trials or pure switch trials in separate blocks
(foreknowledge conditions) or performed both switch and repeat trials within the
same block (non-foreknowledge conditions). In addition, the time interval between
the response to the first task and the onset of the next task's stimulus
(response-stimulus interval, RSI) was set at either 300 ms or 600 ms. Both
stimulus-locked and response-locked lateralized readiness potentials were
measured to examine at what stage in time that task preparation affects the task
performance. The results showed that task preparation had the same amount of
beneficial effect on the stage of response selection for both switch and repeat
trials, regardless of whether the RSI was short or long.
PMID- 17027111
TI - Advances in graphonomics: studies on fine motor control, its development and
disorders.
AB - During the past 20 years graphonomic research has become a major contributor to
the understanding of human movement science. Graphonomic research investigates
the relationship between the planning and generation of fine motor tasks, in
particular, handwriting and drawing. Scientists in this field are at the
forefront of using new paradigms to investigate human movement. The 16 articles
in this special issue of Human Movement Science show that the field of
graphonomics makes an important contribution to the understanding of fine motor
control, motor development, and movement disorders. Topics discussed include
writer's cramp, multiple sclerosis, Parkinson's disease, schizophrenia, drug
induced parkinsonism, dopamine depletion, dysgraphia, motor development,
developmental coordination disorder, caffeine, alertness, arousal, sleep
deprivation, visual feedback transformation and suppression, eye-hand
coordination, pen grip, pen pressure, movement fluency, bimanual interference,
dominant versus non-dominant hand, tracing, freehand drawing, spiral drawing,
reading, typewriting, and automatic segmentation.
PMID- 17027110
TI - Decomposing delta, theta, and alpha time-frequency ERP activity from a visual
oddball task using PCA.
AB - OBJECTIVE: Time-frequency (TF) analysis has become an important tool for
assessing electrical and magnetic brain activity from event-related paradigms. In
electrical potential data, theta and delta activities have been shown to underlie
P300 activity, and alpha has been shown to be inhibited during P300 activity.
Measures of delta, theta, and alpha activity are commonly taken from TF surfaces.
However, methods for extracting relevant activity do not commonly go beyond
taking means of windows on the surface, analogous to measuring activity within a
defined P300 window in time-only signal representations. The current objective
was to use a data driven method to derive relevant TF components from event
related potential data from a large number of participants in an oddball
paradigm. METHODS: A recently developed PCA approach was employed to extract TF
components [Bernat, E. M., Williams, W. J., and Gehring, W. J. (2005).
Decomposing ERP time-frequency energy using PCA. Clin Neurophysiol, 116(6), 1314
1334] from an ERP dataset of 2068 17 year olds (979 males). TF activity was taken
from both individual trials and condition averages. Activity including
frequencies ranging from 0 to 14 Hz and time ranging from stimulus onset to
1312.5 ms were decomposed. RESULTS: A coordinated set of time-frequency events
was apparent across the decompositions. Similar TF components representing
earlier theta followed by delta were extracted from both individual trials and
averaged data. Alpha activity, as predicted, was apparent only when time
frequency surfaces were generated from trial level data, and was characterized by
a reduction during the P300. CONCLUSIONS: Theta, delta, and alpha activities were
extracted with predictable time-courses. Notably, this approach was effective at
characterizing data from a single-electrode. Finally, decomposition of TF data
generated from individual trials and condition averages produced similar results,
but with predictable differences. Specifically, trial level data evidenced more
and more varied theta measures, and accounted for less overall variance.
PMID- 17027112
TI - A probiotic strain of Lactobacillus plantarum stimulates lymphocyte responses in
immunologically intact and immunocompromised mice.
AB - Experimental evidences showing the immunomodulatory effects of probiotic
microorganisms have been provided by studies on immunologically intact animals.
Here we compared the immunomodulation capacity of a probiotic strain of
Lactobacillus plantarum on intact and cyclophosphamide-treated BALB/c mice.
Although this strain fulfilled the in vitro criteria for the selection of
potentially probiotic bacteria (resistance to low pH and bile, adhesion to
epithelial cells and antimicrobial activity), it was unable to establish a
persistent colonization in the gastrointestinal tract after intragastric gavage.
The administration of L. plantarum did not modify the cyclophosphamide-induced
leukopenia, but partially restored the proliferation of spleen cells from
cyclophosphamide-treated mice in response to lipopolysaccharide. Our findings
show that probiotic bacteria may exert immunomodulatory effects despite a limited
colonization ability and may improve the immune function damaged by
immunosuppressive agents.
PMID- 17027113
TI - Expression of recombinant proteins lacking methionine as N-terminal amino acid in
plastids: human serum albumin as a case study.
AB - Removal of the N-terminal methionine of a protein could be critical for its
function and stability. Post-translational modifications of recombinant proteins
expressed in heterologous systems may change amino-terminal regions. We studied
the expression of mature proteins lacking methionine as the N-terminal amino acid
in tobacco chloroplasts, using human serum albumin (HSA) as an example. Two
approaches were explored. First, we fused the Rubisco small subunit transit
peptide to HSA. This chimeric protein was correctly processed in the stroma of
the chloroplast and rendered the mature HSA. The second approach took advantage
of the endogenous N-terminal methionine cleavage by methionine aminopeptidase.
Study of this protein processing reveals a systematic cleavage rule depending on
the size of the second amino acid. Analysis of several foreign proteins expressed
in tobacco chloroplasts showed a cleavage pattern in accordance to that of
endogenous proteins. This knowledge should be taken into account when recombinant
proteins with N-terminus relevant for its function are expressed in plastids.
PMID- 17027114
TI - The DE loop of the domain III of the envelope protein appears to be associated
with West Nile virus neutralization.
AB - The envelope (E) protein of WNV plays an important role in the virus
neutralization. Using a mAb 5E8, a neutralizing epitope on the domain III of the
E of the New York strain of WN virus was characterized. Results from
neutralization-escape mutants and site-directed mutagenesis revealed that the 5E8
epitope is a highly conformation dependent epitope consisting of at least
residues E330, E332 and E367 on the domain III. Besides known critical
neutralizing epitopes E330 and E332, our results indicate that residue E367, a
component of DE loop on the domain III, appeared to be associated with
neutralization but little with neuroinvasion of the virus, as reported previously
(Beasley et al., 2002).
PMID- 17027115
TI - [Camptocormia disclosing Parkinson's disease].
AB - Camptocormia is characterised as an extreme bent-forward posture of the trunk
that disappears in the recumbent position. On X-ray, trunk flexion appears
without vertebral rotation as in scoliosis. The condition is a well-known
complication of Parkinson's disease (PD) at the late stage. The authors present
the case of a 77-year-old woman affected by severe camptocormia, which appeared
and worsened in less than 6 months and hindered gait. Despite no signs of PD,
neuro-imaging (DAT-Scan) showed an L-Dopa transducer decrease in putamens. A few
weeks later, bradykinesia appeared and the clinical diagnosis of PD became more
obvious. L-Dopa improved bradykinesia but did not change the bent-spine posture.
A 1-year follow-up showed no other signs of PD other than bradykinesia, but the
camptocormia was unchanged.
PMID- 17027116
TI - Semi-automated CT segmentation using optic flow and Fourier interpolation
techniques.
AB - In radiotherapy treatment planning, tumor volumes and anatomical structures are
manually contoured for dose calculation, which takes time for clinicians. This
study examines the use of semi-automated segmentation of CT images. A few high
curvature points are manually drawn on a CT slice. Then Fourier interpolation is
used to complete the contour. Consequently, optical flow, a deformable image
registration method, is used to map the original contour to other slices. This
technique has been applied successfully to contour anatomical structures and
tumors. The maximum difference between the mapped contours and manually drawn
contours was 6 pixels, which is similar in magnitude to difference one would see
in manually drawn contours by different clinicians. The technique fails when the
region to contour is topologically different between two slices. A solution is
recommended to manually delineate contours on a sparse subset of slices and then
map in both directions to fill the remaining slices.
PMID- 17027117
TI - Accumulation of p-hydroxybenzoic acid in hairy roots of Daucus carota.
AB - We report here the accumulation of p-hydroxybenzoic acid in Agrobacterium
rhizogenes-induced hairy root cultures of Daucus carota. This phenolic acid finds
application in food, pharmaceutical and polymer industries. Metabolic profiling
of phenolics by HPLC/ESI-MS from these hairy roots showed a considerable amount
of p-hydroxybenzoic acid accumulation both in cytosol and in the cell wall.
Analyses of HCl and NaOH treated soluble phenolic fractions resulted in the
elution of peaks with same retention time and similar UV-absorption spectra as
observed with p-hydroxybenzoic acid standard. This suggests that p-hydroxybenzoic
acid is present in the cytosol as free-form (unconjugated). A correlation has
been drawn between the accumulation of soluble and wall-bound phenolic acids on a
time-course basis. An apparent absence of any p-hydroxybenzoic acid-glucoside
supports this observation, which in turn encourages the idea of its incorporation
in the cell wall in an alkaline-labile form.
PMID- 17027118
TI - Transgenic rice plants ectopically expressing AtBAK1 are semi-dwarfed and
hypersensitive to 24-epibrassinolide.
AB - Brassinosteroids (BRs) are endogenous plant hormones essential for plant growth
and development. Brassinosteroid insensitive1 (BRI1)-assocaiated receptor kinase
(BAK1) is one of the key components in the BR signal transduction pathway due to
its direct association with the BR receptor, BRI1. Although BRI1 and its
orthologs have been identified from both dicotyledonous and monocotyledonous
plants, less is known about BAK1 and its orthologs in higher plants other than
Arabidopsis. This article provides the first piece of evidence that AtBAK1 can
greatly affect growth and development of rice plants when ectopically expressed,
suggesting that rice may share similar BR perception mechanism via BRI1/BAK1
complex. Interestingly, transgenic rice plants displayed semi-dwarfism and
shortened primary roots. Physiological analysis and cell morphology assay
demonstrated that the observed phenotypes in transgenic plants were presumably
caused by hypersensitivity to endogenous levels of BRs, different from BR
insensitive and deficient rice mutants. Consistently, several known BR inducible
genes were also upregulated in transgenic rice plants, further suggesting that
BAK1 was able to affect BR signaling in rice. On the other hand, the transgenic
plants generated by overproducing AtBAK1 may potentially have agricultural
applications because the dwarfed phenotype is generally resistant to lodging,
while the fertility remains unaffected.
PMID- 17027119
TI - Effect of early decrease in the lesion size on late brain tissue loss,
synaptophysin expression and functionality after a focal brain lesion in rats.
AB - The purpose of the present study is to determine the effects of early decrease in
the lesion size on late brain tissue loss, synaptogenesis and functionality after
a focal brain lesion in rats. The lesion was induced either to the cortex using
the photothrombotic ischemic stroke or to the striatum using the malonate
poisoning model. The cortical and striatal lesions amounted to 66-80 mm(3) at day
1 post-lesion and were reduced by 50% after the acute administration of dipyridyl
(a liposoluble iron chelator) and aminoguanidine (an inhibitor of the inducible
nitric oxide synthase), respectively. Loss of histologically intact tissue and
synaptophysin expression as an indicator of synaptogenesis were examined at day
35 post-lesion. Both types of lesion resulted in synaptophysin upregulation in
contralateral and ipsilateral cortical areas. On the contrary, brain tissue loss
was greater after the striatal (-17%) than the cortical lesion (-5%).
Synaptophysin expression and tissue loss were not different between drug- and
vehicle-treated rats. Moreover, a set of standard neurological tests revealed a
difference in deficit between the both types of lesion, yet only in the acute
post-lesion stage. However, it did not distinguish between vehicle- and drug
treated rats whatever the lesion location. Our results indicate that late
histological endpoints measurements are not recommended to probe the potential
neuroprotective properties of a drug administered within the acute post-lesion
stage. They also suggest that inhibition of cytotoxic mechanisms involved in
lesion growth is of no clinical interest when it cannot lead to a long-term
histological protection and/or increased synaptogenesis.
PMID- 17027122
TI - Hepatitis B infection among health workers in Uganda: evidence of the need for
health worker protection.
AB - Hepatitis B exposure was assessed in 311 health workers in Uganda, a highly
endemic country. Health workers were selected by random sampling from a
categorized list of health workers at district level, proportionate to the
population of each district. Whereas 60.1% of health workers have evidence of
hepatitis B infection, with 8.7% being chronic carriers and one (0.3%) acutely
infected, 36.3% are still susceptible and could benefit from vaccination. Only
5.1% reported having had at least one dose of hepatitis B vaccine and 3.5% were
apparently immune through vaccination. Needle stick injuries reported by 77% of
health workers were the most common mode of exposure to blood and body fluids.
Trends suggested duration of service as a predictor while age and history of
blood transfusion remained significant independent risk factors for hepatitis B
infection. 98% of health workers are willing to be vaccinated. These results
confirm the need for protection and vaccination of health workers in Uganda
against hepatitis B.
PMID- 17027123
TI - Development of a DIVA subunit vaccine against Actinobacillus pleuropneumoniae
infection.
AB - Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia
which leads to high economic losses in the swine industry worldwide. Vaccination
against this pathogen is hampered by the occurrence of 15 serotypes, and commonly
used whole cell bacterin vaccines are not sufficiently cross-serotype protective.
In addition, for generating and maintaining specified pathogen-free herds it is
desirable to use DIVA (differentiating infected from vaccinated animals)
vaccines. Based on a detergent wash extraction of outer membrane associated
proteins and secreted proteins we developed a DIVA vaccine using the immunogenic
ApxII toxin which is present in 13 of the 15 A. pleuropneumoniae serotypes as the
DIVA antigen. The apxIIA gene was deleted in one strain each of serotypes 1, 2,
and 5 using a single-step transconjugation system, and equal parts of detergent
washes from these strains served as the vaccine antigen. After intramuscular
immunisation all pigs developed a strong humoral immune response to the vaccine
antigen and showed no reactivity in an ApxIIA ELISA. Upon challenge all pigs were
completely protected from clinical symptoms in trials with a homologous (serotype
2) as well as with a heterologous strain (serotype 9); in addition, colonisation
of the challenge strain was clearly reduced but not abolished completely. As a
result of the highly efficient protection, however, immunised pigs did not
develop antibodies to the DIVA-antigen at levels detectable by ELISA but only by
a more sensitive Western blotting approach, thereby demonstrating the challenge
in developing appropriate marker vaccines for the livestock industry.
PMID- 17027124
TI - Protective immune responses to a multi-gene DNA vaccine against Staphylococcus
aureus.
AB - To investigate the strategy of using a multivalent polyprotein DNA vaccine
against Staphylococcus aureus, a series of plasmids was used to immunize mice
followed by infectious challenge. The plasmid vaccines expressed Clumping factor
A (Clfa), fibronectin binding protein A (FnBPA) and the enzyme Sortase (Srt) as
single proteins or combined as a polyprotein. All animals produced a mixed Th1
and Th2 response including functional antigen-specific, mostly IgG2a antibodies,
sustained production of IFN-gamma and a predominantly CD8+ T-cell response. Upon
challenge with a virulent S. aureus isolate (Sa042), after 21 days, 55% of the
multi-gene vaccinated mice survived infection compared to only 15% of the control
groups. Vaccinated mice showed no signs of arthritis when challenged with the
less virulent "Newman" strain that caused reactive arthritis in the controls. The
results suggest that a multi-gene polyprotein-expressing nucleic acid vaccine
alone produces a combined Th1 and Th2 response that can contribute to protection
against the complex pathogenesis of S. aureus.
PMID- 17027126
TI - A cost-effectiveness analysis of radon protection methods in domestic properties:
a comparative case study in Brixworth, Northamptonshire, UK.
AB - Building regulations in the UK have since 1992 required that radon-proof
membranes be installed in new domestic properties to protect residents against
the adverse effects of radon. This study compares the cost-effectiveness of the
current regulatory regime with an alternative that would entail new properties
being tested for radon after construction, and being remediated if necessary. The
alternative regime is found to be more cost-effective for a sample of properties
in Brixworth, Northamptonshire, UK. For this regime, the central estimate of cost
per quality-adjusted life-year gained, the measure of cost-effectiveness used, is
2869 pounds compared to 6182 pounds for installing membranes, results suggesting
a case for re-examining the current regulations on radon protection in new
properties. Pilot studies will, however, be needed to consider how different
means of protecting residents of new properties against radon might operate in
practice and to provide improved evidence on their relative cost-effectiveness.
PMID- 17027125
TI - Comparative proteomics analysis to annexin B1 DNA and protein vaccination in
mice.
AB - DNA vaccines have been widely reported to elicit both effective humoral and
cellular immune responses, but the mechanisms of antigen processing and
presentation in DNA immunization is still ambiguous. Aiming to molecular
mechanisms involved in DNA immunization, comparative serum proteomics was
introduced to discover differentially expressed proteins after different
immunizations. Using two-dimensional electrophoresis and matrix-assisted laser
desorption ionisation-time-of-flight mass spectrometry, 23 three-fold or greater
up-regulated proteins were separated and identified, including 14 from ANXB1 DNA
immunized mice and 9 from annexin B1 protein immunized mice. The
histocompatibility class I molecule H2-Q10 (HA10_MOUSE) and proteasome activator
PA28 alpha-subunit (PSME1_MOUSE) were found up-regulated in ANXB1 DNA immunized
mice, which may contribute to the augmented activation of T lymphocytes. These
proteins may serve as potential surrogate markers of successful vaccination and
provide research targets for molecular mechanisms of vaccinology.
PMID- 17027127
TI - Changes in the inferior alveolar nerve following sagittal split ramus osteotomy
in monkeys: a comparison of monocortical and bicortical fixation.
AB - We aimed to observe the changes in the inferior alveolar nerve (IAN) after
bilateral sagittal split ramus osteotomy (SSRO) using monocortical or bicortical
screw fixation. Bilateral SSRO for setback of the mandible was done in 12
monkeys, and monocortical or bicortical fixation was applied on opposing sides of
each mandible. Sensory nerve action potentials were tested before and immediately
after operation, and at 2, 4, 8, and 12 weeks. Six animals selected randomly were
killed at 4 and 12 weeks after the operation. Specimens of nerve were harvested
and processed for histological examination and electron microscopic analysis.
Obvious prolongation of latency and diminution of amplitude in the IAN were found
postoperatively. At 4 weeks after operation, Wallerian degeneration was apparent,
and there were signs of axonal regeneration in the nerves. The IAN had more
abnormalities of evoked potentials and pathological changes after bicortical than
after monocortical fixation. Although considerable recovery was found after both
forms of fixation at 12 weeks, the function of the nerve after plate fixation was
better than after screw fixation. Our results suggest that the nerve damage
during SSRO could be temporary and reversible, and monocortical fixation may
result in restoration of the nerve function sooner than bicortical fixation.
PMID- 17027128
TI - Endodontic reoperation using an endoscope and microsurgical instruments: One year
follow-up.
AB - Endodontic reoperation was required for 30 teeth with periapical lesions in 18
patients, using microsurgical instruments and a 6cm long and 3mm wide endoscope
for magnification. Reoperation was successful in 14 patients after 1 year.
PMID- 17027129
TI - Penetrating injury of the facial skeleton through the orbit, by a massive
metallic shotgun block: A case report.
AB - We present a case of invasion of the orbit and the infra-temporal fossa by a
massive breechblock from a shotgun. The block was removed and two months later
the orbit was reconstructed with iliac crest. Six months after that the patient
had plastic surgery and insertion of ocular prosthesis.
PMID- 17027130
TI - Meniscal screw fixation provides sufficient stability to prevent tears from
gapping.
AB - BACKGROUND: Many meniscal fixation implants have low pull-out forces. It is still
unknown if these forces are higher than the forces the implants must resist in
vivo. It was hypothesized that meniscal repair with the meniscal screw as an
example for a device of low pull-out force significantly reduces tear gapping.
METHODS: Longitudinal tears were set in the posterior horn of the medial menisci
of porcine knee joints. To observe the tears a translucent placeholder copying
the original articular surface replaced the medial tibial plateau. The knees were
moved in a loading and motion simulator under various external moments and axial
loads and gapping of the tear was registered. The measurements were repeated
after fixation of the tears with three ClearFix Screws, which show a low pull-out
force of 20N only. FINDINGS: Maximum gapping (median 1.6mm, min/max 1.1/1.8mm)
occurred at 200N axial joint load under the combination of a valgus and external
rotation moment. Fixation with the ClearFix Screw significantly reduced tear
gapping in all load cases. INTERPRETATION: Moderate joint loads only lead to
small gaps of meniscal tears. Meniscal fixation with the ClearFix Screw prevents
longitudinal meniscal tears from gapping. This could indicate from a
biomechanical point of view that fixation implants of low pull-out strength are
not in danger of failure in a normal rehabilitation regimen.
PMID- 17027131
TI - Compositional assessment of event DAS-59122-7 maize using substantial
equivalence.
AB - Event DAS-59122-7 (Herculex RW) maize (Zea mays L.) plants were transformed to
express the Cry34Ab1 and Cry35Ab1 binary insecticidal crystal proteins originally
isolated from Bacillus thuringiensis Berliner (Bt) strain PS149B1. These proteins
protect maize roots from attack by corn rootworms, Diabrotica spp. DAS-59122-7
maize also contains the pat gene, originally isolated from Streptomyces
viridochromogenes, which confers tolerance to glufosinate-ammonium herbicides
(e.g. Liberty). We assessed the composition of these transgenic plants (with and
without Liberty herbicide treatment), grown at a total of eight fields sites over
2 years, by applying the principle of substantial equivalence. Forage and grain
samples were analyzed for proximates, fiber and minerals, and grain was further
analyzed for amino acids, fatty acids, vitamins, secondary metabolites and anti
nutrients. Data plots were prepared that allow for efficient investigation of
equivalency between event DAS-59122-7 maize and a non-transgenic near-isogenic
maize line grown contemporaneously. Results demonstrated that DAS-59122-7 maize
is equivalent to non-transgenic maize with respect to these important
constituents.
PMID- 17027132
TI - Effects of bilateral eye movements on gist based false recognition in the DRM
paradigm.
AB - The effects of saccadic bilateral (horizontal) eye movements on gist based false
recognition was investigated. Following exposure to lists of words related to a
critical but non-studied word participants were asked to engage in 30s of
bilateral vs. vertical vs. no eye movements. Subsequent testing of recognition
memory revealed that those who undertook bilateral eye movement were more likely
to correctly recognise previously presented words and less likely to falsely
recognise critical non-studied associates. This result joins other research in
demonstrating the conditions in which false memory effects can be attenuated.
PMID- 17027133
TI - Posture recognition in Alzheimer's disease.
AB - BACKGROUND: Apraxia is neurologically induced deficit in the ability perform
purposeful skilled movements. One of the most common forms is ideomotor apraxia
(IMA) where spatial and temporal production errors are most prevalent. IMA can be
associated Alzheimer's disease (AD), even early in its course, but is often not
identified possibly because the evaluation of IMA by inexperienced judges using
performance tests is unreliable. The purpose of this study, therefore, is to
learn if the Postural Knowledge Test (PKT), a praxis discrimination test that
assesses knowledge of transitive (PKT-T subtest) and intransitive (PKT-I subtest)
postures and does not require extensive training, is as sensitive and specific as
the praxis performance tests. METHODS: We studied 15 subjects with probable AD as
well as 18 age-matched controls by having them perform transitive and
intransitive gestures to command and imitation, as well as having them
discriminate between correct and incorrect transitive and intransitive postures.
RESULTS: Overall on all tests, the control subjects performed better than those
with AD. In addition all subjects had more trouble with transitive than
intransitive gestures. Using a stepwise discriminative analysis, 81.8% of the
subjects could be classified according to Group (94.4% of Controls, 66.7% of AD
subjects). In this analysis, the PKT-T (transitive posture subtest) was the only
measure that contributed to the discrimination of subjects. CONCLUSION: We found
that having subjects select the correct transitive hand postures in this "booklet
test" was more sensitive than grading their praxis performances even when using
judges with extensive training. This suggests that this discrimination test might
be an excellent means for diagnosing and screening patients for AD. The reason
why recognition of transitive postures is relatively more difficult for our AD
subjects is not known. Two possibilities are that the representations for
intransitive movements are stronger than those for transitive movements, and
hence, more resistant to degradation, or that intransitive acts are stored in
parts of the brain not affected by AD.
PMID- 17027134
TI - Activation of premotor vocal areas during musical discrimination.
AB - Two same/different discrimination tasks were performed by amateur-musician
subjects in this functional magnetic resonance imaging study: Melody
Discrimination and Harmony Discrimination. Both tasks led to activations not only
in classic working memory areas--such as the cingulate gyrus and dorsolateral
prefrontal cortex--but in a series of premotor areas involved in vocal-motor
planning and production, namely the somatotopic mouth region of the primary and
lateral premotor cortices, Broca's area, the supplementary motor area, and the
anterior insula. A perceptual control task involving passive listening alone to
monophonic melodies led to activations exclusively in temporal-lobe auditory
areas. These results show that, compared to passive listening tasks,
discrimination tasks elicit activation in vocal-motor planning areas.
PMID- 17027136
TI - Assessing 12(S)-lipoxygenase inhibitory activity using colorectal cancer cells
overexpressing the enzyme.
AB - 12(S)-Lipoxygenase (LOX) is regarded as a pro-tumorigenic enzyme and as a
potential target for therapy and prevention of cancer so that the search for
specific 12(S)-LOX inhibitors is part of drug development strategies. To
facilitate the identification of specific 12(S)-LOX inhibitors we have created an
assay cell line by introducing a12(S)-LOX expression vector into SW480 colorectal
cancer cells. When arachidonic acid was supplied in the medium both transiently
and stably overexpressing cells produced 12(S)-hydroxytetraenic acid (HETE)
originating from the transfected gene at 4-5-fold the amount obtained from
control transfectants. 12(S)-HETE production was 1913.7+/-17.2pg/ml and reached a
steady state level 24h after addition of arachidonic acid. To demonstrate the
models suitability of 12(S)-LOX overexpressing SW480 cells they were used to
measure the inhibitory activity of the plant phenols baicalein, kaempferol,
quercetin, nordihydroguaretic acid and resveratrol which are known for their
chemopreventive as well as LOX-inhibitory activity in different tumour models.
All 5 compounds inhibited 12(S)-HETE production at concentrations below those
necessary for growth inhibition.
PMID- 17027137
TI - Lack of immunogenicity of ice structuring protein type III HPLC12 preparation
administered by the oral route to human volunteers.
AB - Before a novel protein can be used in foods, its potential allergenicity must be
assessed. In this study, healthy volunteers consumed ice structuring protein
(ISP) Type III preparation or a control material 5 days a week for a total of 8
weeks. General measures of health were recorded during the study, and the
immunogenicity of the protein was assessed by monitoring the levels of IgG and
IgE antibodies specific for ISP Type III. The participants remained in good
health throughout the study and during the 4 week follow-up period. No IgG or IgE
antibodies specific for ISP Type III were detected in the blood of the
participants. Investigations of immunogenicity in man have not been previously
applied in the context of safety evaluation and they do not form part of the
regimens proposed for the evaluation of protein allergenicity. Consequently no
standardised protocols exist for such studies, nor any background against which
to interpret the results. Nevertheless, the absence of an immune response using a
protocol which could have been expected to result in a response with a strongly
immunogenic protein, confirms the conclusions of earlier published work, and
attests to the lack of allergenicity of ISP Type III preparation.
PMID- 17027138
TI - Effects of fluoroquinolones on HERG channels and on pancreatic beta-cell ATP
sensitive K+ channels.
AB - An inhibition of the cardiac rapid delayed rectifier K(+) current (I(Kr)) and of
the ATP-sensitive K(+) (K(ATP)) current seems to be involved in the mechanisms of
the cardiotoxic effects and the alterations in glucose homeostasis, respectively,
induced by some fluoroquinolones. The aim of the present study was to compare the
effects of fluoroquinolone derivatives on the pore-forming subunit of the cardiac
I(Kr), which is encoded by human ether-a-go-go-related gene (HERG), and on the
ATP-sensitive K(+) (K(ATP)) channel from the clonal insulinoma cell line RINm5F.
Sparfloxacin blocked HERG currents half-maximally (IC(50) value) at a
concentration of 33.2 microM, whereas norfloxacin and lomefloxacin each tested at
a concentration of 300 microM inhibited HERG currents only by 2.8+/-3.6% and
12.3+/-4.7%, respectively. Four newly synthesized fluoroquinolone derivatives
with either a p-fluoro-phenyl (compound C3) or an o-fluoro-phenyl (compound C4)
substituent at position N(1) and an additional dimethylated piperazine ring
(compounds C1 and C2) inhibited HERG currents by 7.3-14.7% at test concentrations
of 100 microM. The rank order of potency for the inhibition of K(ATP) currents
was C2>C1, C4, sparfloxacin>C3. In conclusion, the structural requirements for
fluoroquinolones to inhibit I(Kr) currents and K(ATP) currents appear to differ.
The amino group at position C(5) seems to be primarily responsible for the strong
HERG current blocking property of sparfloxacin. In contrast, for the block of
pancreatic beta-cell K(ATP) currents by fluoroquinolones the substituents at
positions N(1), C(7) and C(8) all might play a role.
PMID- 17027139
TI - Clinical wear of posterior metal-free polymer crowns. One-year results from a
randomized clinical trial.
AB - OBJECTIVES: The purpose of this randomized clinical trial was to evaluate the
clinical wear behavior of posterior, metal-free polymer crowns, with and without
a glass-fiber framework, and to compare it with that of metal-ceramic crowns.
METHODS: Eighty single crowns manufactured from a newly designed polymer
composite were set in posterior teeth. Half of these received a glass-fiber
framework (group 1) whereas half were prepared without framework stabilization
(group 2). All polymer crowns were adhesively luted with resin cement. As the
control group, 40 conventional metal-ceramic crowns were inserted with hybrid
cement. Wear was measured, by use of gypsum replicas, at baseline and after 12
months, by use of a 3D laser scanner. Statistical analysis was performed using
mixed-effects regression model analyses. RESULTS: The mean total wear of
posterior single crowns was -8.1 microm (+/-9.7 microm) in group 1, -7.0 microm
(+/-9.1 microm) in group 2, and -3.4 microm (+/-6.3 microm) in the control group.
Statistical analysis revealed wear behavior was significantly different from the
control group for group 1 (p=0.014) and group 2 (p<0.01). No significant
difference was detected between groups 1 and 2. Age, gender, and opposing teeth
had no significant effect on wear behavior. CONCLUSIONS: Within a 12-month
observation period mean total wear of posterior polymer crowns with and without a
glass-fiber framework was significantly greater than for metal-ceramic crowns.
The selection of restorative materials should be based on knowledge of clinical
wear in order to preserve occlusal stability.
PMID- 17027140
TI - A dose-response curve for the negative bias pressure of an intrathoracic pressure
regulator during CPR.
AB - An intrathoracic pressure regulator (ITPR) is a device that can be added to the
external end of a tracheal tube to create controlled negative airway pressure
between positive pressure ventilations. The resulting downward bias of the airway
pressure baseline promotes increased venous return and enhanced circulation
during CPR and also during hypovolemic shock. In the present study, we exercised
a mathematical model of the human cardiopulmonary system, including airways,
lungs, a four chambered heart, great vessels, peripheral vascular beds, and the
biomechanics of chest compression and recoil, to determine the relationship
between systemic perfusion pressure during CPR and the value of baseline negative
airway pressure in an ITPR. Perfusion pressure increases approximately 50% as
baseline airway pressure falls from zero to -10 cm H2O. Thereafter perfusion
pressure plateaus. Negative bias pressures exceeding -10 cm H2O are not needed in
ITPR-CPR.
PMID- 17027141
TI - Short-schedule intravesical gemcitabine with ablative intent in recurrent Ta-T1,
G1-G2, low- or intermediate-risk, transitional cell carcinoma of the bladder.
AB - OBJECTIVES: PRIMARY OBJECTIVE: to assess ablative efficacy and tolerability of
short-schedule intravesical gemcitabine for intact, low- and intermediate-risk,
recurrent superficial bladder tumours. SECONDARY OBJECTIVE: to assess effect on
prophylaxis. METHODS: Patients with a diagnosis of recurrence and a history of
previous superficial, low- or intermediate-risk bladder tumours were selected for
the study. They received 2000 mg gemcitabine in 50 ml, that is 40 mg/ml,
intravesically, weekly for 4 wk, followed by resection of any residual lesions.
Complete responses consisted of absence of any macroscopic, histologically
confirmed, residual lesion, and no response in the presence of residual lesions.
The effect on prophylaxis was measured in months as disease-free interval to
first recurrence, and as percentage of patients recurring within the first 12 mo.
Toxicity was assessed as local and systemic. RESULTS: Of 34 recruited patients,
28 consecutive patients were evaluable, with complete responses observed in 13 of
28 (46.4%) and no response in 15 (53.6%). Median time to first recurrence was 9.1
mo (range: 2.9-26.5) for 19 of 28 (67.8%) patients experiencing recurrence during
the first year. Local or systemic toxicity was observed in 9 of 34 (26.4%)
patients, resulting in protocol interruption in 6 patients. CONCLUSIONS:
Intravesical gemcitabine alone showed ablative efficacy in nearly one half of the
patients under study. Drug tolerability was good, both locally and systemically.
PMID- 17027142
TI - PhotoMEA: an opto-electronic biosensor for monitoring in vitro neuronal network
activity.
AB - PhotoMEA is a biosensor useful for the analysis of an in vitro neuronal network,
fully based on optical methods. Its function is based on the stimulation of
neurons with caged glutamate and the recording of neuronal activity by Voltage
Sensitive fluorescent Dyes (VSD). The main advantage is that it will be possible
to stimulate even at sub-single neuron level and to record with high resolution
the activity of the entire network in the culture. A large-scale view of neuronal
intercommunications offers a unique opportunity for testing the ability of drugs
to affect neuronal properties as well as alterations in the behaviour of the
entire network. The concept and a prototype for validation is described here in
detail.
PMID- 17027143
TI - A bio-inspired visual collision detection mechanism for cars: combining insect
inspired neurons to create a robust system.
AB - The lobula giant movement detector (LGMD) of locusts is a visual interneuron that
responds with an increasing spike frequency to an object approaching on a direct
collision course. Recent studies involving the use of LGMD models to detect car
collisions showed that it could detect collisions, but the neuron produced
collision alerts to non-colliding, translating, stimuli in many cases. This study
presents a modified model to address these problems. It shows how the neurons pre
synaptic to the LGMD show a remarkable ability to filter images, and only
colliding and translating stimuli produce excitation in the neuron. It then
integrates the LGMD network with models based on the elementary movement detector
(EMD) neurons from the fly visual system, which are used to analyse directional
excitation patterns in the biologically filtered images. Combining the
information from the LGMD neuron and four directionally sensitive neurons
produces a robust collision detection system for a wide range of automotive test
situations.
PMID- 17027145
TI - Positive feedback of hepatic angiotensinogen expression in silver sea bream
(Sparus sarba).
AB - The renin-angiotensin system (RAS) is involved in the maintenance of fluid
homeostasis in vertebrates. Production of the precursor protein, angiotensinogen,
is regulated by other components within the RAS. Angiotensin II (Ang II)
stimulates the production and secretion of angiotensinogen in many mammalian
models. However, the existence of a similar positive feedback mechanism for
angiotensinogen has not been demonstrated for any non-mammalian species. In the
present study, we have cloned the angiotensinogen for silver sea bream (Sparus
sarba) and investigated the role of Ang II on angiotensinogen expression. The
nucleotide sequence of angiotensinogen for S. sarba only exhibits a fair
resemblance to other fish angiotensinogens and shows 76.6% similarity to that of
Takifugu rubripes and 57.2% similarity to that of Danio rerio. Angiotensinogen
transcripts have been identified in the brain, liver, kidney, and various parts
of the intestine of sea bream, an observation, which probably implies the
presence of a local RAS at the tissue level. The liver is probably the major
source of angiotensinogen, as it exhibits the highest angiotensinogen transcript
abundance among different tissues. Differential angiotensinogen expression was
found among different regions of the intestine where the pyloric caeca exhibits
the highest expression. Putative Ang I is identified at the N-terminal of the
deduced protein with a novel sequence [Asn1, Ile5, His9]-Ang I. Hepatic
angiotensinogen expression in sea bream adapted to different salinities remained
constant and this is probably due to desensitization of the angiotensin receptors
by angiotensin. A positive feedback mechanism of angiotensinogen by Ang II has
been demonstrated as exogenous Ang II increased the amount of angiotensinogen
transcript in isolated hepatocytes in vitro. Blockade of endogenous RAS by the
angiotensin converting enzyme (ACE) inhibitor, captopril, significantly lowered
the hepatic expression of angiotensinogen in vivo. The effect of Ang II
stimulation on angiotensinogen expression is more potent in fish than that in
mammals. These data suggest that the positive feedback mechanism of
angiotensinogen by Ang II has already evolved in teleosts and such mechanism may
be involved in the maintenance of angiotensinogen secretion under resting and
hypertensive conditions.
PMID- 17027146
TI - Efects of growth hormone and cadmium on the transcription regulation of two
metallothionein isoforms.
AB - The effect of growth hormone (GH) and cadmium (Cd) on metallothionein (MT)
expression was investigated in hepatoma cells. In fish the constitutive isoform
MT-B and the metal-responsive MT-A are expressed. Real-time RT-PCR revealed that:
Cd up-regulates mostly MT-A, GH slightly induces MT-B and the GH/Cd combination
induces synergistically both MTs. Perturbations in Ca2+ levels suppressed or
reduced the Cd-induction of MTs and abolished the GH/Cd synergy. Similar results
were obtained by inhibition of tyrosine kinases. Also the signaling molecules
recruited by the GH receptor responded differently to GH and Cd, with ERKs
showing a synergistic activation upon GH/Cd. The following conclusions can be
drawn: (1) cytosolic Ca2+ is mainly involved in MT-A regulation; (2) both Ca2+
and tyrosine phosphorylation are essential for Cd-induction and GH/Cd synergy on
MTs. The synergy could depend on interactions in different signaling pathways,
leading to a differential recruitment of MTF-1 and AP-1 transcription factors.
PMID- 17027144
TI - Differential regulation of CREB and ERK phosphorylation through corticotropin
releasing factor receptors type 1 and 2 in AtT-20 and A7r5 cells.
AB - The corticotropin-releasing factor (CRF) family of peptides generally exerts its
biological actions by binding to two major subtypes of CRF receptors: CRF
receptor type 1 (CRF1 receptor) and CRF receptor type 2 (CRF2 receptor). In this
study, we investigated the mechanism by which three ligands altered
phosphorylation of CREB and ERK 1/2, using AtT-20 cells (expressing CRF1
receptor) and A7r5 cells (expressing CRF2 receptor). Incubation with 100 nM of
CRF, urocortin 1 (UCN 1), or UCN 2 increased CREB phosphorylation. The protein
kinase A pathway was involved in the CRF- or UCN-mediated increase in CREB
phosphorylation in both cell lines. Bisindolylmaleimide partially inhibited the
CRF-mediated increase in CREB phosphorylation, but only in AtT-20 cells,
suggesting that the protein kinase C pathway is involved in regulation of CREB
phosphorylation via CRF1 receptor but not CRF2 receptor. CRF increased ERK
phosphorylation in AtT-20 cells, whereas the UCNs decreased it in A7r5 cells.
Bisindolylmaleimide partially inhibited the UCN-mediated decrease in ERK
phosphorylation in A7r5 cells, suggesting that the protein kinase C pathway is
partially involved in CRF2 receptor signal transduction. In AtT-20 cells, the
mitogen-activated protein kinase kinase pathway regulated ERK phosphorylation
following CRF1 receptor activation. These findings suggest differential
regulation of CREB and ERK 1/2 phosphorylation through CRF receptors.
PMID- 17027147
TI - Alternative splicing in angiogenesis: the vascular endothelial growth factor
paradigm.
AB - Alternative splicing, first discovered in the 1970s, has emerged as one of the
key generators of proteomic diversity. Not surprisingly, alternative splicing is
increasingly linked to the etiology of cancer. This is illustrated by vascular
endothelial growth factor (VEGF), the dominant angiogenic factor. Recently, an
antiangiogenic family of VEGF isoforms was discovered, and termed VEGF(xxx)b.
VEGF(xxx)b isoforms arise from an alternative 3' splice site in exon 8, and
differ by a mere six amino acids at the C-terminus. These alternative six amino
acids radically change the functional properties of VEGF. VEGF(xxx)b isoform
expression is regulated in human tissues and development, and disregulated in
many pathological states including cancer. Understanding what regulates
VEGF(xxx)b alternative splicing, and therefore the balance of pro- and
antiangiogenic isoforms is of great importance and will be explored in detail
over the next few years.
PMID- 17027148
TI - The retinoid X receptor-selective ligand, LGD1069, inhibits tumor-induced
angiogenesis via suppression of VEGF in human non-small cell lung cancer.
AB - The present study determined the influence of a retinoid X receptor agonist
LGD1069 on angiogenesis in non-small cell lung cancer. In A549 xenograft models,
treatment with LGD1069 inhibited the growth and CD31 expression compared with
control. In vivo angiogenesis assay utilizing hollow fiber, LGD1069 reduced
density of capillary network induced by tumor cells. To determine the basis of
these observations, we examined the expression of VEGF and activation of JNK and
ERK in A549 cells exposed to LGD1069. Our data showed that LGD1069 decrease the
VEGF expression of tumor cells in a dose-dependent manner. Furthermore, it was
demonstrated that the decreasing expression of VEGF was consist with inhibition
of JNK and ERK activation induced by LGD1069. Collectively, our results suggest a
role of LGD1069 in treatment for non-small cell lung cancer by inhibition of
tumor-induced angiogenesis.
PMID- 17027149
TI - Neural drive preservation after detraining following neuromuscular electrical
stimulation training.
AB - The purpose of the study was to investigate the behaviour of the central nervous
system when 5 weeks of neuromuscular electrical stimulation (NMES) training was
followed by 5 weeks of detraining. Nineteen males were divided into the
neuromuscular electrostimulated group (EG, n=12) and the control group (CG, n=7).
The training program consisted of 15 sessions of isometric NMES over a 5-week
period. The EG subjects were tested before training (PRE), after 5 weeks of NMES
training (POST) and after 5 weeks of detraining (DE) while CG subjects were only
tested at PRE and at POST. Soleus (SOL) and gastrocnemii (GAS) maximal H-reflex
and M-wave potentials were evoked at rest (i.e., H(max) and M(max), respectively)
and during maximal voluntary contraction (MVC) (i.e., H(sup) and M(sup),
respectively). SOL and GAS V-wave were recorded by supramaximal stimulation
delivered during MVC. SOL and GAS electromyographic (EMG) activity as well as
muscle activation were also assessed during MVC. After training, plantar flexor
MVC increased significantly by 22% (P<0.001). Torque gains were associated with
an increase in muscle activation (P<0.05), SOL and GAS normalized EMG activity
(P<0.01 and P<0.05, respectively) and V/M(sup) ratios (P<0.01 and P<0.05,
respectively). No significant changes occurred in any of these parameters between
POST and DE. H(max)/M(max) and H(sup)/M(sup) ratios for both muscles were
unchanged after both the training and detraining periods. In conclusion, the NMES
training-induced neural adaptations were maintained after detraining, suggesting
that neural changes are long-lasting and did not affect the elements of H-reflex
pathways.
PMID- 17027150
TI - Distribution of choline acetyltransferase immunoreactivity in the alimentary
tract of the barnacle Balanus amphitrite (Cirripedia, Crustacea).
AB - To date only peptidergic innervation has been described in the alimentary tract
of barnacles. In the present work the presence and distribution of choline
acetyltransferase (ChAT), the acetylcholine (ACh) synthesizing enzyme, was
investigated by immunohistochemistry in the alimentary tract of the adult
barnacle Balanus amphitrite. Numerous ChAT-immunoreactive (IR) cells and a net of
ChAT-IR cytoplasmic processes were localized inside the epithelium of the
posterior midgut, close to the basement membrane; no IR nerve endings were
detected in the midgut longitudinal and circular muscle bundles. Epithelial
neurons or endocrine cells in the gut epithelium have been described in some
invertebrate species belonging to different taxa and their peptidergic features
are reported in the literature. Our results point out the presence of
neuroepithelial cells also in the gut epithelium of barnacles; moreover, for the
first time, a cholinergic feature is suggested for this cell type. These data
seem to indicate the involvement of ACh in the gut functions of barnacle and
suggest that the barnacle alimentary tract is more complex than previously
thought and requires further study.
PMID- 17027151
TI - Potential participation of cystatin C in rapid eye movement sleep (REMS)
modulation.
AB - It has been hypothesized that proteins modulate rapid eye movement sleep (REMS).
Studies have shown an increase in the liberation of proteins in the mesencephalic
reticular formation of cats during REMS. It has also been determined that protein
synthesis inhibitors diminish REMS and that protease-inhibitors increase this
sleep phase. These and other studies support the importance of "di novo" protein
molecules in sleep, and in particular, in REMS regulation. In this context, it is
important to determine the role of endogenous proteases and their endogenous
inhibitors in sleep regulation. In this study, we found that Cystatin C (CC), an
endogenous protease inhibitor, diminishes wakefulness and increases REMS. We have
also found an increase in CC expression after REMS deprivation and a tendency to
decrease after a 2 h period of REMS rebound. We further showed that REMS
deprivation increases the expression of Cathepsin H (CH), a protease inhibited by
CC. These results suggest that naturally occurring protease-inhibitors enhance
REMS, perhaps by facilitating the availability of proteins.
PMID- 17027152
TI - Association analysis of NAD(P)H:quinone oxidoreductase gene 609 C/T polymorphism
with Alzheimer's disease.
AB - Alterations of the NAD(P)H:quinone oxidoreductase (NQO1) activity are associated
with Alzheimer's disease (AD). A polymorphism consisting of a single nucleotide
(C-->T) change at position 609 of NQO1 influences the NQO1 activity. Therefore
the NQO1 C609T polymorphism may confer susceptibility for AD developing. To test
the hypothesis, we have performed an association study between the NQO1 gene
polymorphism C609T and late-onset Alzheimer's disease (LOAD) in Chinese
population. Totally 104 LOAD patients and 128 controls were enrolled in our data
set. All subjects were genotyped for NQO1 and Apolipoprotein E (APOE). There were
no significant differences in NQO1 genotype or allele frequencies between cases
and controls. Likewise, with the stratification of APOE psilon4 status, no
statistical difference was observed between cases and controls. Our findings
suggested that this polymorphism might not represent additional genetic risk
factor for LOAD. However, the present study cannot exclude NQO1 as a possible
candidate for LOAD. Further study in a larger population and biological
functional analysis of NQO1 gene is required to verify the role of NQO1 in LOAD.
PMID- 17027153
TI - Response delay and spatial representation in pointing movements.
AB - Pointing movements decrease in accuracy when target information is removed before
movement onset. This time effect was analyzed in relation with the spatial
representation of the target location, which can be egocentric (i.e. in relation
to the body) or exocentric (i.e. in relation to the external world) depending on
the visual environment of the target. The accuracy of pointing movements
performed without visual feedback was measured in two delay conditions: 0 and 5-s
delay between target removal and movement onset. In each delay condition, targets
were presented either in the darkness (egocentric localization) or within a
structured visual background (exocentric localization). The results show that
pointing was more accurate when targets were presented within a visual background
than in the darkness. The time-related decrease in accuracy was observed in the
darkness condition, whereas no delay effect was found in the presence of a visual
background. Therefore, contextual factors applied to a simple pointing action
might induce different spatial representations: a short-lived sensorimotor
egocentric representation used in immediate action control, or a long-lived
perceptual exocentric representation which drives perception and delayed action.
PMID- 17027154
TI - Use of the Faces Pain Scale by left and right hemispheric stroke patients.
AB - No pain scale is available for stroke patients due to the presence of language or
cognitive disorders. However, the Faces Pain Scale (FPS), which was initially
developed for children, has been used with success in adults with cognitive
impairments. The aim of this study is to test whether the FPS could be used in
left or right hemispheric stroke patients (LHSP, RHSP). One hundred twenty-seven
stoke patients and 21 controls were recruited in 2 rehabilitation units.
Construct validity of FPS was assessed by rating and ranking facial expressions.
FPS was correlated to a Visual Analog Scale (VAS) and to a Verbal Rating Scale
(VRS) for the assessment of shoulder pain. Reliability was determined by test
retest procedures. Performances of RHSP in the ranking and rating procedures were
very poor compared to LHSP and to controls. However, in the assessment of
patients' shoulder pain, FPS scores were highly correlated with VAS and VRS in
both stroke groups (r=0.65-0.82, p<10(-3)). FPS was more reliable in LHSP than in
RHSP. It was preferred to VAS and VRS in LHSP, while in RHSP VAS was the
preferred scale. The present study provides preliminary support for the validity
and the reliability of FPS in LHSP. However, we do not recommend its sole use in
stroke patients. Further studies are needed to determine whether FPS can be used
in stroke patients for assessing changes in severity of pain over time.
PMID- 17027155
TI - Stereotyped topography of different elevated contingent negative variation
components in children with migraine without aura points towards a subcortical
dysfunction.
AB - Increased negativity during contingent negative variation (CNV) is thought to
reflect abnormal neural activation in adult migraineurs' attention related
processing. Findings in childhood and adolescence have yielded less clear
results. This study characterizes the age-dependent development of CNV topography
in migraine during childhood in order to elucidate the origin and cerebral
generators of described CNV elevations. A large sample of children with primary
headache (migraine with/without aura, tension type headache) and healthy controls
aged 6-18 years was examined in a CNV paradigm using 64-channel high resolution
DC-EEG. Patients were tested for diagnose-related topographic group differences
of initial CNV (iCNV), late CNV (lCNV) and postimperative negative variation
(PINV). All three CNV components of 6-11-year-old migraineurs without aura showed
elevated negativity over the supplementary motor area (SMA) and around the
vertex. Migraine children lacked age-dependent development of late CNV around Cz
as previously reported. However, they showed a normal development of late CNV
over pre-/primary motor cortex (MI). There was no marked elevation of iCNV
amplitude over frontal areas (orienting reaction) nor specific amplitude
elevations over "motor" or "sensory" areas during sustained attention (late CNV).
Additional "pre-mature" activation e.g., in the locus coeruleus (leading to
diffuse cortical activation summing up to a maximum over the vertex) or the basal
ganglia (interacting with SMA) explained the rather stereotyped CNV elevation
around the vertex better than a specific implication of the cortical systems
responsible for orienting, motor preparation or sensory attention.
PMID- 17027156
TI - Two rare clinical manifestations of coenurosis in sheep.
AB - Two rare clinical manifestations of coenurosis in sheep are reported. (i) A case
of partial seizure disorder in a ram of 11 months old. During seizure episodes
the animal lay down in lateral recumbency displaying initially a stuporous
condition and subsequently began to revolve its head from the base of the cervix.
At the necropsy of the case, Coenurus cerebralis cyst (young bladder worm) was
found dorsally inside the brainstem, in the site of the tectum mesencephaly. (ii)
The second-reported manifestation was a bacterial meningoengephalitis that was
witnessed in two lambs of 6-7 weeks old. The lambs displayed lateral recumbency
with seizure activity. At necropsy, meningoencephalitis with congestion and
abscesses were observed in both of them. Interestingly, C. cerebralis cysts were
also found in both brains. Streptococcus dysgalactiae was isolated from the
abscesses. Possibly, S. dysgalactiae translocation of the blood-brain barrier was
facilitated by the migration of the immature stages of C. cerebralis to and
through the brain.
PMID- 17027157
TI - Anticoccidial effect of green tea-based diets against Eimeria maxima.
AB - Anticoccidial effects of green tea (GT)-based diets were evaluated in chickens
following oral infection with Eimeria maxima an ubiquitous intestinal parasite of
poultry that impairs the growth and feed efficiency of infected birds. Five-week
old chickens were assigned to four groups (GT 0.5%, GT 2.0%, untreated/infected
and non-infected control) and each group consisted of 15 chickens. Chickens were
fed a standard diet supplemented with ground green tea for 2 weeks prior to
infection with E. maxima (10,000 sporulated oocysts per bird). The effects of
green tea on E. maxima infection were assessed by two parameters, fecal oocyst
shedding and body weight gain. The green tea-fed chickens produced significantly
reduced fecal oocysts (P<0.05) when compared to the E. maxima-infected group fed
standard diet. The green tea-based diet, however, did not improve body weight
loss caused by E. maxima infection. This study is the first to demonstrate
anticoccidial effect of green tea on Eimeria parasites.
PMID- 17027158
TI - Therapeutic and persistent efficacy of spinosad applied as a pour-on or a topical
spray against natural infestations of chewing and sucking lice on cattle.
AB - Studies were conducted in Wisconsin and Illinois, USA, to assess and compare the
therapeutic and persistent efficacy of spinosad when applied as either a pour-on
or topical spray and compared with cyfluthrin pour-on and coumaphos topical spray
for controlling natural infestations of chewing (Bovicola bovis) and sucking
(Linognathus vituli, Solenopotes capillatus and Haematopinus eurysternus) lice on
cattle. Thirty-five animals at each trial site were blocked according to pre
treatment lice counts and randomly allocated to one of five treatment groups:
single treatments of spinosad (25 g/L), diluted with water to 0.04% active
ingredient and applied as a whole-body topical spray; spinosad (25 g/L) applied
as a neat pour-on at 2 mg/kg body weight; Co-Ral Emulsifiable Livestock
Insecticide (5.8% coumaphos), diluted to 0.03% active ingredient and applied as a
whole-body topical spray; CyLence Pour-on Insecticide (1% cyfluthrin), applied as
a neat pour-on at the manufacturer's recommended use rate for lice; and untreated
control. Both spinosad treatments and cyfluthrin provided > or =96% control of B.
bovis for up to 7 weeks, whereas the efficacy of coumaphos dropped to <90% after
week 5 at one site. Spinosad spray had the best therapeutic and residual control
of all treatments against L. vituli, > or =98% for at least 5 weeks at both
sites, compared with 3 weeks for coumaphos at one site. Spinosad and coumaphos
sprays provided 100% control of S. capillatus for at least 8 weeks compared with
> or =97% control for spinosad and cyfluthrin pour-on treatments over the same
interval. While H. eurysternus burden was low and limited to one study site, all
four treatments provided 100% control for at least 6 weeks. These studies showed
that topically applied spinosad provided a high degree of therapeutic and
residual control against both sucking and chewing lice.
PMID- 17027159
TI - Cellular senescence and cancer treatment.
AB - Cellular senescence, an irreversible cell-cycle arrest, reflects a safeguard
program that limits the proliferative capacity of the cell exposed to endogenous
or exogenous stress signals. A number of recent studies have clarified that an
acutely inducible form of cellular senescence may act in response to oncogenic
activation as a natural barrier to interrupt tumorigenesis at a premalignant
level. Paralleling the increasing insights into premature senescence as a tumor
suppressor mechanism, a growing line of evidence identifies cellular senescence
as a critical effector program in response to DNA damaging chemotherapeutic
agents. This review discusses molecular pathways to stress-induced senescence,
the interference of a terminal arrest condition with clinical outcome, and the
critical overlap between premature senescence and apoptosis as both tumor
suppressive and drug-responsive cellular programs.
PMID- 17027160
TI - Methemoglobinemia by cerium nitrate poisoning.
AB - Cerium nitrate is a topical antiseptic used with silver sulfadiazine
(Flammacerium) for the treatment of serious burns. This topical agent can induce
methemoglobinemia, but no cases have been reported in the recent literature. In
this article, we present the case of a 16-year old girl, with third-degree burns
over 95% of her body. After daily dressings of Flammacerium, on the sixth day she
developed a bluish skin coloring. When tested for methemoglobinemia, levels of
31.8% were found. These returned to normal after classic treatment with Methylene
blue.
PMID- 17027161
TI - Treatment of flexion contractures following burns in extremities.
AB - In order to release and cover defects in burn contractures over joints, several
surgical procedures have been proposed. Skin grafting is easy to do, but it
requires immobilization, and tends to contract again, different types of flaps
without skin grafting are alternatives. These flaps have their specific
indications, limitations and some disadvantages such as a bulky, unattractive
appearance in donor or recipient sites, partial necrosis, and sometimes patients
dissatisfaction. Considering these points, the authors proposed a new technique
composed of a Y-V advancement in the middle and two scar releases proximal and
distal to the joint which were covered with full thickness skin grafts. This
seems to have some advantages in both case of technique and more patients
satisfaction. In the current study, the authors presented their results with
different methods of treatment, which they performed for burn flexion
contractures in limbs. Ninety-one operations were performed in 74 patients, the
method of reconstruction included skin grafting in 43 contractures, local flaps
in 16, pediculated flaps in 11, and the new combined approach in 21 cases. Width
of scar was one of the main factors for selection of choice option. This proposed
technique is especially appropriate for scars which cover 10-60% of joint surface
area. Advantages of this combined technique are coverage of joint area with a
pretty normal skin flap, and enough scar lengthening due to combination of Y-V
advancement and skin grafted released areas.
PMID- 17027162
TI - Neuropeptide Y regulates recurrent mossy fiber synaptic transmission less
effectively in mice than in rats: Correlation with Y2 receptor plasticity.
AB - A unique feature of temporal lobe epilepsy is the formation of recurrent
excitatory connections among granule cells of the dentate gyrus as a result of
mossy fiber sprouting. This novel circuit contributes to a reduced threshold for
granule cell synchronization. In the rat, activity of the recurrent mossy fiber
pathway is restrained by the neoexpression and spontaneous release of
neuropeptide Y (NPY). NPY inhibits glutamate release tonically through activation
of presynaptic Y2 receptors. In the present study, the effects of endogenous and
applied NPY were investigated in C57Bl/6 mice that had experienced pilocarpine
induced status epilepticus and subsequently developed a robust recurrent mossy
fiber pathway. Whole cell patch clamp recordings made from dentate granule cells
in hippocampal slices demonstrated that, as in rats, applied NPY inhibits
recurrent mossy fiber synaptic transmission, the Y2 receptor antagonist (S)-N2
[[1-[2-[4-[(R,S)-5,11-dihydro-6(6H)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2
oxoethyl]cyclopentyl]acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H
1,2,4-triazol-4-yl]ethyl]-argininamide (BIIE0246) blocks its action and BIIE0246
enhances synaptic transmission when applied by itself. Y5 receptor agonists had
no significant effect. Thus spontaneous release of NPY tonically inhibits
synaptic transmission in mice and its effects are mediated by Y2 receptor
activation. However, both NPY and BIIE0246 were much less effective in mice than
in rats, despite apparently equivalent expression of NPY in the recurrent mossy
fibers. Immunohistochemistry indicated greater expression of Y2 receptors in the
mossy fiber pathway of normal mice than of normal rats. Pilocarpine-induced
status epilepticus markedly reduced the immunoreactivity of mouse mossy fibers,
but increased the immunoreactivity of rat mossy fibers. Mossy fiber growth into
the inner portion of the dentate molecular layer was associated with increased Y2
receptor immunoreactivity in rat, but not in mouse. These contrasting receptor
changes can explain the quantitatively different effects of endogenously released
and applied NPY on recurrent mossy fiber transmission in mice and rats.
PMID- 17027164
TI - Glutamate reduces secretion of l-serine in astrocytes isolated from stroke-prone
spontaneously hypertensive rats.
AB - In the CNS, l-serine (l-Ser) plays an essential role in neuronal survival by
evoking a variety of biological responses in glial cells. Initially, we examined
whether glutamate, hydrogen peroxide (H(2)O(2)), interleukin-1 (IL-1) beta, and
sodium nitroprusside (SNP) induce the secretion of l-Ser in astrocytes isolated
from Wistar Kyoto rats (WKY). The secretion of l-Ser was significantly induced
with glutamate and SNP in cultured astrocytes. Next, to gain insight into the
involvement of l-Ser in glutamate-induced neuroprotection, we compared the
secretion of l-Ser in astrocytes isolated from stroke-prone spontaneously
hypertensive rats (SHRSP) and normotensive rats, WKY. We also examined the mRNA
expression of the enzyme that produces l-Ser, 3-phosphoglycerate dehydrogenase
(PHGDH), and a neural amino acid transporter, ASCT1, in the cultured astrocytes.
A dose-dependent study of glutamate in astrocytes of SHRSP indicated differences
in the secretion of l-Ser, and gene expression of PHGDH and ASCT1, compared with
levels in the WKY astrocytes. We demonstrated that both the secretion and the
gene expression were significantly attenuated in glutamate-treated astrocytes
from SHRSP. Cerebral ischemia in SHRSP induced a massive efflux of glutamate,
causing delayed neuronal death in region CA1 of the hippocampus. The results
suggest that the attenuated secretion of l-Ser in astrocytes is involved in
neuronal vulnerability and survival in SHRSP during the production of glutamate,
as the secretion of l-Ser, which is stimulated by glutamate, is closely related
to the protective effect against glutamate-mediated neurotoxicity. We conclude
that glutamate and SNP up-regulate the secretion of l-Ser in primary astrocytes.
Secretion of l-Ser is regulated in astrocytes in response to glutamate and nitric
oxide and may correspond to the level of l-Ser needed for neuronal survival
during brain insults such as ischemic stroke in SHRSP.
PMID- 17027163
TI - Fos responses of dopamine neurons to sociosexual stimuli in male zebra finches.
AB - Dopamine (DA) is produced in numerous brain areas and influences a wide variety
of social behaviors, but very few data are available to establish the socially
relevant response properties of most DA populations, which comprise eight cell
groups numbered A8-A15. Anatomically, these DA populations are evolutionarily
conserved, and all have been identified in both birds and mammals. We now report
the Fos responses of tyrosine hydroxylase-immunoreactive (TH-ir; putatively
dopaminergic) neurons in the A8-A15 cell groups of male zebra finches following
exposure to a control condition or one of six different social stimuli: a
heterospecific male, conspecific male, fighting in a mate competition paradigm
(which includes both male and female stimuli), a courtship interaction without
physical contact, a courtship interaction with physical contact but no mounting,
and a courtship interaction with mounting. We found that the DA cell groups
exhibit distinctive profiles of responsiveness to social stimuli. Fos induction
in A8, A9, A10 and midbrain A11 neurons increased significantly in response to a
variety of conspecific stimuli, but not heterospecific stimuli. In contrast, Fos
induction in the preoptic A14 neurons was observed specifically in response to
sexual interactions, and Fos induction in hypothalamic A11 neurons appears to
primarily reflect the performance of courtship singing. Infundibular A12 neurons,
which may be involved in stress-related processes, showed the highest level of
TH+Fos colocalization in control subjects. This colocalization decreased in
response to all conspecific stimuli except fighting, and did not decrease
following exposure to a heterospecific male.
PMID- 17027165
TI - Muscle inflammation induces a rapid increase in calcitonin gene-related peptide
(CGRP) mRNA that temporally relates to CGRP immunoreactivity and nociceptive
behavior.
AB - Recent data support an important role for calcitonin gene-related peptide (CGRP)
in deep tissue nociceptive processing. Using real-time reverse transcriptase
polymerase chain reaction (RT-PCR), radioimmunoassay, immunohistochemistry and
behavioral testing, we studied the early time course of CGRP mRNA and protein
expression as well as nociceptive behavior following muscle inflammation. A rapid
and significant increase in CGRP mRNA occurred in the mandibular division (V3) of
the ipsilateral trigeminal ganglion at 30 minutes, 4 and 24 h after the injection
of complete Freund's adjuvant as an inflammatory agent into rat masseter muscle.
No change in mRNA occurred in the ipsilateral ophthalmic and maxillary divisions
(V1/V2) or in the contralateral V3. The levels of immunoreactive calcitonin gene
related peptide (iCGRP) in the ipsilateral V3 significantly increased at 1, 4 and
24 h following muscle inflammation. In contrast, no change occurred in iCGRP
levels in either the ipsilateral V1/V2 or contralateral V3. When saline was
injected into the masseter muscle, the levels of mRNA or iCGRP did not change in
the ipsilateral V3 suggesting that the biochemical changes are specific to CFA
induced muscle inflammation. The number of muscle afferent neurons immunoreactive
for CGRP was significantly reduced compared with control at 1, 4 and 24 h in the
ipsilateral but not in the contralateral trigeminal ganglion following
inflammation. This decrease in the ipsilateral ganglion may indicate a loss of
intrasomatic CGRP as a result of increased axonal transport away from the
neuronal cell body and/or release of CGRP. Behavioral testing showed a reduction
in head withdrawal thresholds bilaterally from 30 min through 24 h following
muscle inflammation. Thus upregulation of CGRP mRNA and iCGRP levels are
temporally related to the development of inflammation and lowered pain
thresholds. The present data support the hypothesis that CGRP is upregulated
during deep tissue inflammation and suggest that gene transcription is involved
in this upregulation.
PMID- 17027166
TI - Subcellular localization of nicotinamide adenine dinucleotide phosphate oxidase
subunits in neurons and astroglia of the rat medial nucleus tractus solitarius:
relationship with tyrosine hydroxylase immunoreactive neurons.
AB - Superoxide produced by the enzyme nicotinamide adenine dinucleotide phosphate
(NADPH) oxidase mediates crucial intracellular signaling cascades in the medial
nucleus of the solitary tract (mNTS), a brain region populated by
catecholaminergic neurons, as well as astroglia that play an important role in
autonomic function. The mechanisms mediating NADPH oxidase (phagocyte oxidase)
activity in the neural regulation of cardiovascular processes are incompletely
understood, however the subcellular localization of superoxide produced by the
enzyme is likely to be an important regulatory factor. We used immunogold
electron microscopy to determine the phenotypic and subcellular localization of
the NADPH oxidase subunits p47(phox), gp91(phox,) and p22(phox) in the mNTS in
rats. The mNTS contains a large population of neurons that synthesize
catecholamines. Significantly, catecholaminergic signaling can be modulated by
redox reactions. Therefore, the relationship of NADPH oxidase subunit labeled
neurons or glia with respect to catecholaminergic neurons was also determined by
dual labeling for the superoxide producing enzyme and tyrosine hydroxylase (TH),
the rate-limiting enzyme in catecholamine biosynthesis. In the mNTS, NADPH
oxidase subunits were present primarily in somatodendritic processes and
astrocytes, some of which also contained TH, or were contacted by TH-labeled
axons, respectively. Immunogold quantification of NADPH oxidase subunit
localization showed that p47(phox) and gp91(phox) were present on the surface
membrane, as well as vesicular organelles characteristic of calcium storing
smooth endoplasmic reticula in dendritic and astroglial processes. These results
indicate that NADPH oxidase assembly and consequent superoxide formation are
likely to occur near the plasmalemma, as well as on vesicular organelles
associated with intracellular calcium storage within mNTS neurons and glia. Thus,
NADPH oxidase-derived superoxide may participate in intracellular signaling
pathways linked to calcium regulation in diverse mNTS cell types. Moreover, NADPH
oxidase-derived superoxide in neurons and glia may directly or indirectly
modulate catecholaminergic neuron activity in the mNTS.
PMID- 17027167
TI - The vasopressin 1b receptor is prominent in the hippocampal area CA2 where it is
unaffected by restraint stress or adrenalectomy.
AB - The vasopressin 1b receptor (Avpr1b) is one of two principal receptors mediating
the behavioral effects of vasopressin (Avp) in the brain. Avpr1b has recently
been shown to strongly influence social forms of aggression in mice and hamsters.
This receptor appears to play a role in social recognition and motivation as well
as in regulating the hypothalamic-pituitary-adrenal axis. Most of these studies
have been performed in knockout mice, a species in which the localization of the
Avpr1b has not been described, thus precluding correlations with the behaviors.
We performed in situ hybridization histochemistry (ISHH) with specific probes and
found especially prominent expression within the CA2 pyramidal neurons of the
hippocampus, with much lower expression in the hypothalamic paraventricular
nucleus and amygdala. Reverse transcriptase-polymerase chain reaction (RT-PCR)
confirmed expression in those as well other areas in which the ISHH was not
sensitive enough to detect labeled cells (e.g. piriform cortex, septum, caudate
putamen and lower brainstem areas). Mouse Avpr1b transcript levels were not
altered in the CA2 field by restraint stress or adrenalectomy. Finally, ISHH and
RT-PCR showed expression of the Avpr1b gene in the rat and human hippocampi as
well. We suggest that the CA2 field may form or retrieve associations (memories)
between olfactory cues and social encounters.
PMID- 17027168
TI - Contribution of epoxyeicosatrienoic acids to the hypoxia-induced activation of
Ca2+ -activated K+ channel current in cultured rat hippocampal astrocytes.
AB - Brief hypoxia differentially regulates the activities of Ca(2+)-activated K(+)
channels (K(Ca)) in a variety of cell types. We investigated the effects of
hypoxia (<2% O(2)) on K(Ca) channel currents and on the activities of cytochrome
P450 2C11 epoxygenase (CYP epoxygenase) in cultured rat hippocampal astrocytes.
Exposure of astrocytes to hypoxia enhanced macroscopic outward K(Ca) current,
increased the open state probability (NPo) of 71 pS and 161 pS single-channel
K(Ca) currents in cell-attached patches, but failed to increase the NPo of both
the 71 pS and 161 pS K(Ca) channel currents recorded from excised inside-out
patches. The hypoxia-induced enhancement of macroscopic K(Ca) current was
attenuated by pretreatment with tetraethylammonium (TEA, 1 mM) or during
recording using low-Ca(2+) external bath solution. Exposure of astrocytes to
hypoxia was associated with generation of superoxide as detected by staining of
cells with the intracellular superoxide detection probe hydroethidine (HE),
attenuation of the hypoxia-induced activation of unitary K(Ca) channel currents
by superoxide dismutation with tempol, and as quantitated by high-pressure liquid
chromatography/fluorescence assay using HE as a probe. In cultured astrocytes in
which endogenous CYP epoxygenase activity has been inhibited with either
miconazole or N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MSPPOH)
hypoxia failed to increase the NPo of both the 71 pS and 161 pS K(Ca) currents
and generation of superoxide. Hypoxia increased the level of P450 epoxygenase
protein and production of epoxyeicosatrienoic acids (EETs) from cultured
astrocytes, as determined by immunohistochemical staining and LC/MS analysis,
respectively. Exogenous 11,12-EET increased the NPo of both the 71 pS and 161 pS
K(Ca) single-channel currents only in cell-attached but not in excised inside-out
patches of cultured astrocytes. These findings indicate that hypoxia enhances the
activities of two types of unitary K(Ca) currents in astrocytes by a mechanism
that appears to involve CYP epoxygenase-dependent generation of superoxide and
increased production or release of EETs.
PMID- 17027169
TI - Galanin inhibits neural activity in the subfornical organ in rat slice
preparation.
AB - The activation of the subfornical organ (SFO), a circumventricular organ, induces
water intake and vasopressin release. Since central administrations of galanin
(GAL) suppress water intake and vasopressin release, GAL may inhibit the neural
activity of SFO neurons. In the present study, we investigated effects of GAL on
the SFO using molecular biological, electrophysiological and anatomical
techniques. Reverse transcription-polymerase chain reaction analysis demonstrated
the presence in the SFO of rats of the mRNAs for each of the three known GAL
receptor subtypes (GalR1, GalR2 and GalR3). In extracellular recordings in SFO
slice preparations, GAL dose-dependently inhibited the neural activity of cells
from a number of recording sites. Many GAL-sensitive SFO neurons showed
excitatory responses to angiotensin II (ANGII). The GalR1 agonist M617 inhibited
the activity of SFO neurons, whereas the GalR2 and GalR3 agonist GAL(2-11) had
almost no effect. In patch-clamp recordings, GAL induced an outward current in
SFO neurons without influencing synaptic currents. An immunoelectron microscopic
study revealed the existence of GAL-containing synaptic vesicles in the SFO.
These results suggest that the SFO has neural inputs involving GAL. The response
to GAL is inhibitory, mediated at least in part by GalR1 and provides a plausible
explanation for the opposite effects of ANGII and GAL seen in vivo on water
intake and vasopressin release.
PMID- 17027170
TI - Metallothionein-I and -III expression in animal models of Alzheimer disease.
AB - Previous studies have described altered expression of metallothioneins (MTs) in
neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and
Alzheimer's disease (AD). In order to gain insight into the possible role of MTs
in neurodegenerative processes and especially in human diseases, the use of
animal models is a valuable tool. Several transgenic mouse models of AD amyloid
deposits are currently available. These models express human beta-amyloid
precursor protein (AbetaPP) carrying different mutations that subsequently result
in a varied pattern of beta-amyloid (Abeta) deposition within the brain. We have
evaluated the expression of MT-I and MT-III mRNA by in situ hybridization in
three different transgenic mice models of AD: Tg2576 (carrying AbetaPP harboring
the Swedish K670N/M671L mutations), TgCRND8 (Swedish and the Indiana V717F
mutations), and Tg-SwDI (Swedish and Dutch/Iowa E693Q/D694N mutations). MT-I mRNA
levels were induced in all transgenic lines studied, although the pattern of
induction differed between the models. In the Tg2576 mice MT-I was weakly
upregulated in cells surrounding Congo Red-positive plaques in the cortex and
hippocampus. A more potent induction of MT-I was observed in the cortex and
hippocampus of the TgCRND8 mice, likely reflecting their higher amyloid plaques
content. MT-I upregulation was also more significant in Tg-SwDI mice, especially
in the subiculum and hippocampus CA1 area. Immunofluorescence stainings
demonstrate that astrocytes and microglia/macrophages surrounding the plaques
express MT-I&II. In general, MT-I regulation follows a similar but less potent
response than glial fibrillary acidic protein (GFAP) expression. In contrast to
MT-I, MT-III mRNA expression was not significantly altered in any of the models
examined suggesting that the various MT isoforms may have different roles in
these experimental systems, and perhaps also in human AD.
PMID- 17027171
TI - A vital role for voltage-dependent potassium channels in dopamine transporter
mediated 6-hydroxydopamine neurotoxicity.
AB - 6-Hydroxydopamine (6-OHDA), a neurotoxic substrate of the dopamine transporter
(DAT), is widely used in Parkinson's disease models. However, the molecular
mechanisms underlying 6-OHDA's selectivity for dopamine neurons and the injurious
sequelae that it triggers are not well understood. We tested whether ectopic
expression of DAT induces sensitivity to 6-OHDA in non-dopaminergic rat cortical
neurons and evaluated the contribution of voltage-dependent potassium channel
(Kv)-dependent apoptosis to the toxicity of this compound in rat cortical and
midbrain dopamine neurons. Cortical neurons expressing DAT accumulated dopamine
and were highly vulnerable to 6-OHDA. Pharmacological inhibition of DAT
completely blocked this toxicity. We also observed a p38-dependent Kv current
surge in DAT-expressing cortical neurons exposed to 6-OHDA, and p38 antagonists
and Kv channel blockers were neuroprotective in this model. Thus, DAT-mediated
uptake of 6-OHDA recruited the oxidant-induced Kv channel dependent cell death
pathway present in cortical neurons. Finally, we report that 6-OHDA also
increased Kv currents in cultured midbrain dopamine neurons and this toxicity was
blocked with Kv channel antagonists. We conclude that native DAT expression
accounts for the dopamine neuron specific toxicity of 6-OHDA. Following uptake, 6
OHDA triggers the oxidant-associated Kv channel-dependent cell death pathway that
is conserved in non-dopaminergic cortical neurons and midbrain dopamine neurons.
PMID- 17027172
TI - Analysis of the variation in use-dependent inactivation of high-threshold
tetrodotoxin-resistant sodium currents recorded from rat sensory neurons.
AB - This study addressed variation in the use-dependent inactivation (UDI) of high
threshold tetrodotoxin-resistant Na+ currents (TTX-R currents) and action
potential firing behavior among acutely isolated rat dorsal root ganglion (DRG)
cells. UDI was quantified as the percent decrease in current amplitude caused by
increasing the current activation rate from 0.1-1.0 Hz for 20 s. TTX-R current
UDI varied from 6% to 66% among 122 DRG cells examined, suggesting the existence
of two or more levels of UDI. The voltage-dependency of the TTX-R currents was
consistent with Na(V)1.8, regardless of UDI. However, TTX-R currents with more
UDI had a more negative voltage-dependency of inactivation, a greater tendency to
enter slow inactivation, and a slower recovery rate from slow inactivation,
compared with those with less UDI. TTX-R currents with more UDI ran down faster
than those with less UDI. However, UDI itself changed little over time,
regardless of the initial UDI level observed in a particular DRG cell. Together,
these two observations suggest that individual DRG cells did not express mixtures
of TTX-R channels that varied regarding UDI. TTX-R current UDI was correlated
with expression of a low-threshold A-current and whole-cell capacitance,
suggesting that it varied among different nociceptor types. Whole-cell inward
currents (WCI-currents), recorded without channel blockers, also exhibited UDI.
WCI-current UDI varied similarly to TTX-R current UDI in magnitude, and relative
to whole-cell capacitance and A-current expression, suggesting that the WCI
currents were carried predominantly by TTX-R channels. DRG cells with more WCI
current UDI exhibited a greater decrease in action potential amplitude and
number, and a greater increase in action potential threshold over seven ramp
depolarizations, compared with DRG cells with less WCI-current UDI. Variation in
UDI of Na(V)1.8 channels expressed by different nociceptor types could contribute
to shaping their individual firing patterns in response to noxious stimuli.
PMID- 17027173
TI - Multisensory processing via early cortical stages: Connections of the primary
auditory cortical field with other sensory systems.
AB - It is still a popular view that primary sensory cortices are unimodal, but recent
physiological studies have shown that under certain behavioral conditions primary
sensory cortices can also be activated by multiple other modalities. Here, we
investigate the anatomical substrate, which may underlie multisensory processes
at the level of the primary auditory cortex (field AI), and which may, in turn,
enable AI to influence other sensory systems. We approached this issue by means
of the axonal transport of the sensitive bidirectional neuronal tracer
fluorescein-labeled dextran which was injected into AI of Mongolian gerbils
(Meriones unguiculatus). Of the total number of retrogradely labeled cell bodies
(i.e. cells of origin of direct projections to AI) found in non-auditory sensory
and multisensory brain areas, approximately 40% were in cortical areas and 60% in
subcortical structures. Of the cell bodies in the cortical areas about 82% were
located in multisensory cortex, viz., the dorsoposterior and ventroposterior,
posterior parietal cortex, the claustrum, and the endopiriform nucleus, 10% were
located in the primary somatosensory cortex (hindlimb and trunk region), and 8%
in secondary visual cortex. The cortical regions with retrogradely labeled cells
also contained anterogradely labeled axons and their terminations, i.e. they are
also target areas of direct projections from AI. In addition, the primary
olfactory cortex was identified as a target area of projections from AI. The
laminar pattern of corticocortical connections suggests that AI receives
primarily cortical feedback-type inputs and projects in a feedforward manner to
its target areas. Of the labeled cell bodies in the subcortical structures,
approximately 90% were located in multisensory thalamic, 4% in visual thalamic,
and 6% in multisensory lower brainstem structures. At subcortical levels, we
observed a similar correspondence of retrogradely labeled cells and anterogradely
labeled axons and terminals in visual (posterior limitans thalamic nucleus) and
multisensory thalamic nuclei (dorsal and medial division of the medial geniculate
body, suprageniculate nucleus, posterior thalamic cell group, zona incerta), and
in the multisensory nucleus of the brachium of the inferior colliculus.
Retrograde, but not anterograde, labeling was found in the multisensory pontine
reticular formation, particularly in the reticulotegmental nucleus of the pons.
Conversely, anterograde, but no retrograde, labeling was found in the visual
laterodorsal and lateroposterior thalamic nuclei, in the multisensory
peripeduncular, posterior intralaminar, and reticular thalamic nuclei, as well as
in the multisensory superior and pericentral inferior colliculi (including
cuneiform and sagulum nucleus), pontine nuclei, and periaqueductal gray. Our
study supports the notion that AI is not merely involved in the analysis of
auditory stimulus properties but also in processing of other sensory and
multisensory information. Since AI is directly connected to other primary sensory
cortices (viz. the somatosensory and olfactory ones) multisensory information is
probably also processed in these cortices. This suggests more generally, that
primary sensory cortices may not be unimodal.
PMID- 17027174
TI - Stress dysfunctions as a unifying paradigm for illness: repairing relationships
instead of individuals as a new gateway for medicine.
AB - Stress has been implicated as a risk factor for most diseases, but a mechanistic
explanation behind such associations remains elusive. As emergent responses to
stress, adaptations range from acute responses where extant system capabilities
mitigate current stress, to longer-term responses where system plasticity buffers
against future stress. The long compendium of human ailments manifests through a
much shorter set of symptoms that may operate through the stress axis. We propose
a unifying ontology for human illnesses that classifies stress dysfunctions
according to types of Darwinian dysfunction - inadequate response with adequate
adaptation, inadequate adaptation, inappropriate adaptation, and epiphenomena of
adaptation. Examples include cancer as a bystander effect of increased biologic
plasticity in response to stress, and infectious illness as a manifestation of
mutually escalating stress in an otherwise commensal relationship between hosts
and microbes. We explore the contributing role of man-made stresses that have
emerged as humans increasingly remodel their environment. Examples include
biologic decompensation associated with reliance on technology to buffer stress,
and behavioral stress caused by the dislocation of kin networks that promotes
illegitimate signaling. Dysfunctional relationships engender stress not only
among humans, but also among individual organs; heart failure, renal failure, and
carotid stenosis may represent examples of such conditions. If stress dysfunction
is the Occam's razor of human illnesses, and derangements in biologic
relationships induce stress dysfunctions, then the study of relationships - an
incarnation of systems biology - may represent a new gateway for medicine.
PMID- 17027175
TI - Analysis of the potential of retroviral gene vectors produced on yeast
intracellular membranes.
PMID- 17027176
TI - Possible magnetic multifunctional nanoplatforms in medicine.
AB - Recently, magnetic nanoparticles have attracted attention because of their
potential in biomedicine. They can be applied to special medical techniques, such
as separation, immunoassay, magnetic resonance imaging (MRI), drug delivery, and
hyperthermia, and so on. But these nanoparticles only have one or two kinds of
functions and cannot realize multipurpose. Therefore, we propose that it is need
to constitute magnetic multifunctional nanoplatforms, which not only have
delivery property of gene vector and drug carrier, but also have heating property
of thermseeds in the alternative magnetic field. Recent trials have proved that
gene therapy combined with chemotherapy and hyperthermia achieves better results
than single therapy strategy. But this is difficult in clinical practice. With
the development of the magnetic multifunctional nanoplatforms, the combined
treatment is feasible in clinical practice. This nanoplatforms is versatile, and
can be applied to wide fields. The use of magnetic multifunctional nanoplatforms
will further improve medical techniques.
PMID- 17027177
TI - Identification of staphylococcal cassette chromosome mec encoding methicillin
resistance in Staphylococcus aureus isolates at Charles Nicolle Hospital of
Tunis.
AB - Staphylococcal cassette chromosome is a mobile element that carries the gene mecA
mediating the methicillin resistance in staphylococci. In Staphylococcus aureus
five types of SCCmec have been described, which differs in size and genetic
composition among strains. SCCmec typing of 34 non redundant methicillin
resistant S. aureus (MRSA) recovered in 2004 at Charles Nicolle Hospital of Tunis
was carried out. The isolates were identified by conventional methods.
Methicillin resistance was detected by oxacillin and cefoxitin disks and
confirmed by mecA PCR. The SCCmec complex types were determined by using PCR
which amplify a sequence overlapping the right SCCmec chromosome junction.
Strains were recovered mainly from cutaneous pus (61.7%) and blood cultures
(17.64%). They were isolated from different wards: medicine (53.1%) especially
from dermatology (41.2%); surgery (40.6%) and pediatrics (3.1%). Only two strains
were community-acquired MRSA. Two strains (5.9%) were harboring SCCmec type I;
five (14.7%) SCCmec type II and 27 (79.4%) SCCmec type III. The two community
acquired MRSA were harboring type II and III SCCmec, usually found in hospital
acquired MRSA. Our findings indicate that there are only three SCCmec types at
Charles Nicolle Hospital. However, the existence of SCCmec types II and III in
community incite us to investigate more community-acquired MRSA.
PMID- 17027178
TI - Dynamics of Puumala virus infection in bank voles in Ardennes department
(France).
AB - The hantaviruses (genus Hantavirus, family Bunyaviridae) include human pathogens
and occur worldwide. In Western and Central Europe, the predominant serotype is
Puumala (PUU) virus, which causes epidemic nephropathy. Voles are considered to
be the main reservoir and the vector of PUU virus. A total of 719 rodents (mainly
Clethrionomys glareolus, Apodemus sp.) trapped by capture-mark-recapture (CMR) in
four sites in Ardennes department (France) between April 2004 and October 2005
were tested for the presence of PUU virus antibodies by enzyme-linked
immunosorbent assay (ELISA). The predominant species, C. glareolus (86.5% [622 of
719]), also had the highest antibody prevalence (37.6% [291 of 773]). In C.
glareolus, the antibody prevalence rate increased with age (weight) in site A, B
and D, reaching more than 50% in the heaviest weight, and suggesting that
horizontal infection may be important.
PMID- 17027179
TI - [Use of BioRad plating agar MRSASelect for the daily detection of methicillin
resistant staphylococci isolated from samples taken from blood culture bottles].
AB - Within a medium size general biology laboratory, it is not always easy to set up
rapid methods for detection of methicillin-resistant staphylococci (detection of
the mecA gene or PLP2a). Since we already use BioRad chromogenic plating agar
MRSASelect for the detection of carriers of methicillin resistant Staphylococcus
aureus, we wanted to test its use on samples taken from blood culture bottles.
Between December 2004 and October 2005, all the blood bottle cultures that
detected positive by direct examination for Gram positive cocci and suspected to
be staphylococci, that is 45 pairs of blood cultures and 3 joint aspirations,
were inoculated on quarter plates of both MRSASelect and standard non-selective
agar. After culture, they were screened by the disc method. No mismatch was
observed between the cultures themselves or the highlighting of methicillin
resistance in either Staphylococcus aureus isolates or for coagulase-negative
staphylococci, regardless of species. Furthermore, the red colour of
Staphylococcus aureus on the medium allowed visualisation of the colonies after
only about ten hours incubation, thus giving the clinician rapid warning of
suspected methicillin resistant Staphylococcus aureus. In addition, in
polymicrobial cultures the different colour of the colonies of Staphylococcus
aureus (red) and coagulase-negative staphylococci (white) is extremely useful.
PMID- 17027180
TI - [Caenorhabditis elegans: in vivo study model of bacterial virulence].
AB - The nematode Caenorhabditis elegans presents many advantages as a model system.
The worm has recently emerged as a potentially useful tool for the study of host
pathogen interactions. This paper presents advantages and inconveniences of this
model, the variety of bacterial pathogens studied, and its use to monitor
virulence of Extraintestinal Escherichia coli strains.
PMID- 17027181
TI - [Contribution of PCR for detection of Mycobacterium tuberculosis complex in
respiratory and nonrespiratory specimens].
AB - AIM OF THE STUDY: To evaluate the sensitivity of PCR versus culture of complex
tuberculosis mycobacteria and to determine the delay between PCR results and
identification of mycobacteria in culture. MATERIALS AND METHODS: Ninety-nine
pulmonary and 66 extrapulmonary specimens were analyzed. Samples were inoculated
on liquid (MGIT, Bactec) and solid media (Coletsos) and respectively incubated 6
and 12 weeks. Identification was performed by reverse hybridization of PCR
products to their complementary probes immobilized on membrane strips (Genotype
MTBC, HAIN). Specimens DNA detection was realized by PCR (Cobas Amplicor
Mycobacterium tuberculosis test, Roche). RESULTS: Sensitivity of PCR for acid
fast bacilli smear positive pulmonary (50/50) and extrapulmonary (7/7) specimens
was 100%. Delay between PCR result and identification was 11 days for pulmonary
specimens and 8 days for extrapulmonary specimens. Sensitivity of PCR for smear
negative samples was, respectively, of 78.7% (37/47) and 51.8% (29/56) for
pulmonary and extrapulmonary specimens. In case of PCR positive result of a smear
negative sample, a gap of respectively 13 and 12 days was obtained for pulmonary
and extrapulmonary specimens compared to identification. CONCLUSION: Positive PCR
result for respiratory specimens allows a gap of 11 to 13 days in diagnosis in
comparison with identification of mycobacteria in culture.
PMID- 17027182
TI - [Uncomplicated urinary tract infections, what about fosfomycin and nitrofurantoin
in 2006?].
AB - Since 2000 to 2005 we assessed the prevalence of antimicrobial resistance among
uropathogens causing acute uncomplicated urinary tract infections (UTI). A total
of 19 618 bacteria were studied, fosfomycin, fluoroquinolones, nitrofurantoin
were in vitro the most potent drugs with more than 80% of susceptibility. If we
compare year 2000 to 2005 we observed a significant decrease of susceptibility
for fluoroquinolones. For the same point of comparison, fosfomycin and
nitrofurantoin showed a favourable evolution. Rationale and prudent use of
antibiotics must now moved us to prescribe parsimoniously fluoroquinolones
especially for some indications such as uncomplicated UTI though there are some
others "old antibiotics" with a role may be underestimated for this specific
indication.
PMID- 17027183
TI - [Comparative susceptibility evolution in Escherichia coli from urinary tract
infections in outpatients and inpatients at Perpignan hospital in 2002 and 2004].
AB - The medical emergency ward makes a link between outpatients and hospitalized
ones, so we can study community bacterial ecology. The antibiotic susceptibility
in Escherichia coli strains isolated from urinary tract infections (UTI) of
patients consulting at emergency ward of our hospital in 2002 and 2004 was
determined and compared with the susceptibility of the same strains isolated from
UTI of hospitalized patients on the same period. The antibiotic susceptibility
was performed with Microscan (Dade Behring). All bacteria were tested against the
following antimicrobial agents: amoxicilline (Amx), l'amoxicilline+clavulanic
acid (AMC), nalidixic acid (NA), ciprofloxacine (Cip), cotrimoxazole (SXT),
nitrofurantoin (Ft). Susceptibility in E. coli strains isolated from outpatients
vary from 58 to 54% for Amx, from 88 to 83% for NA, from 96 to 89% for Cip, from
82 to 79% for SXT, from 94 to 96% for Ft and remains at 60% for AMC from 2002 to
2004. Susceptibility in E. coli strains isolated from hospitalized patients vary
from 52 to 47% for Amx, 55 to 53% for AMC, from 79 to 70% for NA, from 87 to 79%
for Cip, from 74 to 69% for SXT, from 93 to 92% for Ft. Susceptibility in E. coli
strains isolated in the community from UTI outpatients is decreasing and it
becomes worrying particularly concerning the fluoroquinolones, therefore empiric
treatment of pyelonephritis by fluoroquinolones must be assessed again.
PMID- 17027184
TI - [Direct and fast detection of methicillin resistant Staphylococcus aureus
carriage by automated nucleic acid extraction and real time PCR].
AB - We have developed a real time PCR assay for methicillin resistant Staphylococcus
aureus (MRSA) screening able to provide a result in less than 3 h. The PCR
amplifies a 184 bp fragment corresponding to the junction area between mecA and
orfX genes that allows specific identification of MRSA in a nonsterile specimen.
1481 nasal swabs taken from geriatrics, dialysis and intensive care patients were
compared with traditional bacteriology. A short centrifugation, preliminary to
the extraction, with "SETS" system allows a recovery of the sample. The automated
DNA extraction is carried out by the MagNA Pure LC and the PCR by the
LightCycler. The agreement between the two methods is 97.7%. A study of
sensitivity and specificity on 1111 samples respectively gives 75 and 98% for the
real time PCR and, 64 and 99% for the culture. The strategy of fast and effective
tracking that we propose is of an undeniable contribution in the fight against
the MRSA infections.
PMID- 17027185
TI - [HIV controllers: a homogeneous group of HIV-1 infected patients with a
spontaneous control of viral replication].
AB - We identified a group of chronically HIV-1-infected patients in whom viral
replication is spontaneously controlled without antiretroviral treatment. These
patients account for less than 1% of HIV-infected patients. They are defined
according to a virological definition: plasma viral load less than 400 copies
RNA/ml in more than 90% of the samples tested and HIV positive serology known for
more than 10 years. They should never have received antiretroviral therapy. The
CD4 T cell count is not taken into account, which differenciate these patients
from long-term non progressors. Fifteen patients HIV controllers have been
studied in a preliminary work with two main results: i) the demonstration of a
strong HIV-specific CD8 immune response and ii) the amount of viral DNA in PBMCs
is very low and stable along the time. The aim of the ANRS EP36 study group is to
precize the immunological and virological characteristics of these patients.
First data seem to confirm an essential role of CD8 T cells to control viral
replication, the absence of defective virus, and a normal susceptibility of the
CD4 T cells from these patients to the infection with various HIV strains. This
group of patients is homogeneous and its study supports physiopathological
studies. To go further, a national survey of these patients has been set up to
allow future study.
PMID- 17027186
TI - Streptococcus pneumoniae thoracic empyema in children: rapid diagnosis by using
the Binax NOW immunochromatographic membrane test in pleural fluids.
AB - AIM: To evaluate an immunochromatographic membrane test for Streptococcus
pneumoniae antigen (Binax NOW, Inverness medical France) applied to pleural fluid
samples. METHODS: Binax NOW was applied to the pleural fluids of 69 children with
thoracic empyema, in comparison with conventional culture and molecular
techniques. RESULTS: Binax NOW was positive on all 15 pleural fluid samples that
yielded S. pneumoniae in culture, on two samples that yielded S. oralis and S.
salivarius in culture and on 34 culture-negative samples. Fifteen of these 34
culture-negative samples were retrospectively tested by PCR methods, and 14 were
shown to contain S. pneumoniae DNA. Thus, S. pneumoniae was identified by culture
in 22% of samples and by Binax NOW in 69% of samples. CONCLUSION: Binax NOW may
thus be useful for rapid diagnosis of S. pneumoniae thoracic empyema.
PMID- 17027187
TI - [Treatment of localised lung cancer].
AB - This paper focuses on stage I, II and IIIA non-small cell lung cancer treatable
with local treatment. It addresses five questions raised by strategies combining
local treatments with chemotherapy. Even if chemotherapy increases resectability
of stage III disease, the chemotherapy-surgery combination has not been
demonstrated to increase survival compared to the standard chemo-radiation
treatment. The results of the study by Van Meerbeeck do not support this
hypothesis. Does surgery, added to chemo-radiotherapy, improve the outcome in
stage IIIAN2 disease? This was the question addressed by the study by K. Albain.
There is probably not clear cut answer. However, the trimodality strategy might
be interesting in patients undergoing a lobectomy and might have a negative
impact when a pneumonectomy has been performed. In patients with a non
resectable/inoperable cancer treated with standard chemoradiation, the
concomitant strategy has been shown to be superior to sequential treatment.
However, due to acute toxicity, it should be delivered to selected patients, who
still need to be better defined. The chemotherapy-surgery combination is becoming
standard (in stage II disease) and most cooperative groups will probably stand in
favour of it in 2006. The best respective timing for chemotherapy and surgery is
still debated. There are many advantages in favour of preoperative chemotherapy,
including better feasibility and the higher proportion of patients who can
benefit. However, there is no statistically reliable demonstration of such
superiority.
PMID- 17027188
TI - [Hepatic steatosis: an emerging cause of cirrhosis in HIV patients].
AB - Hepatic steatosis is an emerging cause of morbidity in antiretroviral therapy
(ART)-experienced HIV patients. The influence of steatosis on fibrosis is poorly
understood. We report two cases of rapid evolution of disseminated macrovacuolar
steatofibrosis to cirrhosis. Both patients had no history of alcohol abuse, nor
intravenous drug use and were tested negative for HCV (PCR RNA) and had no HBS
antigen. Patient 1 had a past history of hypertrygliceridemia, but controlled
with dietetic measures for 4 years prior to biopsy. The first hepatic biopsy
showed a disseminated macrovacuolar steatosis (>80%). The patient had then
cytolysis and an uncontrolled HIV viral load. The second biopsy was performed two
years later, and HIV was controlled by a new line of ART. It showed a regression
of the steatosis (10%) and a progression of the fibrosis with signs of cirrhosis.
Patient 2 had a long history of HIV infection. He also had an uncontrolled
dyslipidemia. The first biopsy was realised during a period of uncontrolled HIV
infection and elevated liver enzymes. The biopsy showed a major macrovacuolar
steatosis (>80%). The second biopsy was realised 6 years after and showed the
same steatosis and signs of cirrhosis. The HIV infection was then under control.
Observations reported here show a rapid evolution of liver steatosis to cirrhosis
in HIV positive / HCV negative patients, despite the control of HIV infection.
The implication of HAART remains unclear. In the era of HAART, liver steatosis
can rapidly evoluate to cirrhosis without any risk factor except ART.
PMID- 17027189
TI - [Evaluation of four immunoenzymatic tests for detecting Clostridium difficile
toxins A and B].
AB - Four immunoenzymatic tests for detecting Clostridium difficile toxins A and B
were studied: two rapid tests (Tox A/B QUIK CHEK-Techlab and NoviView Toxine-A
Hiss diagnostics) and two Elisa tests (C. difficile TOX A/B II -Techlab and Toxin
A+B Elisa Test, Novitec-Hiss diagnostics). The results were compared to those
obtained with ImmunoCard Tox A+B -ICTAB (Meridian), C. difficile Toxine A (Oxoid)
for rapid test and Elisa Premier A+B Meridian for Elisa. A total of 41 stools and
16 isolates were studied with rapid tests. On stools, the sensitivity and
specificity of QUIK CHEK test was 94.1% and 100% respectively compared to the
test ICTAB. On the isolates, sensitivity and specificity was 100%. With the
Noviview test, the sensitivity on stools and isolates was respectively 88.2 and
85.7% and the specificity was 100% compared to Oxoid. A total of 38 stools were
studied with Elisa tests. With Techlab test compared to the test Premier,
sensitivity and specificity was 100%. The Novitec test gave five false negative
reactions with consequently a sensitivity of 70.6%.
PMID- 17027190
TI - Resistance to antibiotics in clinical isolates of Pseudomonas aeruginosa.
AB - OBJECTIVES: To analyse the global resistance to some antibiotics used to treat
nosocomial infections by Pseudomonas aeruginosa, specially to carbapenems, and
its relationship with the presence of carbapenemases, OXA, VIM and IMP. METHODS:
The study included 229 P. aeruginosa isolates from a Hospital in Northern Spain
(year 2002). Susceptibility to antimicrobial agents was determined by the
analysis of the MIC. Genetic typing was carried out by RAPD-PCR fingerprinting
with primer ERIC-2. Genetic experiments to detect class-1 integrons were
performed by PCR with primers 5'CS and 3'CS. Detection of carbapenemases was done
by phenotypic (Hodge test and DDST) and genotypic methods (PCR with primers for
imp, vim1, vim2 and oxa40 genes). RESULTS: 23.9% of isolates were resistant to
ceftazidime, 35.9% to cefotaxime, 5.3% to amikacin, 54.9% to gentamicin, 14.6% to
imipenem and 6.6% to meropenem. Isolates resistant to imipenem (33) were
furtherly tested. Genetic typing didn't show clonal relatedness among the most of
the isolates. Class-1 integrons were present in most isolates (sizes 600-1700
bp). Phenotypic methods for carbapenemases showed 5 positive isolates. Genotypic
methods showed the presence of two isolates with the oxa40 gene. CONCLUSIONS:
Meropenem, amikacin and imipenem were the most active agents to treat infections
caused by Pseudomonas aeruginosa. In our study, the presence of carbapenemase
enzymes wasn't high. Phenotypic tests cannot be considered as accurate screening
tool to detect carbapenemases. This is the fist report of the oxa40 gene in
Pseudomonas aeruginosa isolates.
PMID- 17027191
TI - [Recurrence of hepatitis C virus (HCV) infection after liver transplantation for
HCV-related disease: host factors and viral factors implicated in the occurrence
and the severity of HCV recurrence].
AB - Cirrhosis due to chronic infection by hepatitis C virus (HCV), associated or not
to a primary hepatocarcinoma, has become the first indication of liver
transplantation. Graft reinfection by HCV is considered to be systematic while
its prognosis is variable from one patient to another. A better knowledge of
factors implicated in the occurrence and severity of hepatitis C recurrence is
crucial in order to make optimal patients' monitoring. This article aims to
present available data in this field, clarifying the role of viral factors (viral
load, genotype, evolution of viral quasispecies) and host-related factors (immune
response) which could take part in the development of hepatitis C recurrence.
PMID- 17027192
TI - [Automated RNA amplification for the rapid identification of Mycobacterium
tuberculosis complex in respiratory specimens].
AB - Rapid and sensitive detection of Mycobacterium tuberculosis complex (MTB)
directly on clinical respiratory specimens is essential for a correct management
of patients suspected of tuberculosis. For this purpose PCR-based kits are
available to detect MTB in respiratory specimen but most of them need at least 4
hours to be completed. New methods, based on TRC method (TRC: Transcription
Reverse transcription Concerted--TRCRapid M. Tuberculosis--Tosoh Bioscience,
Tokyo, Japon) and dedicated monitor have been developed. A new kit (TRC Rapid M.
tuberculosis and Real-time monitor TRCRapid-160, Tosoh Corporation, Japan)
enabling one step amplification and real-time detection of MTB 16S rRNA by a
combination of intercalative dye oxazole yellow-linked DNA probe and isothermal
RNA amplification directly on respiratory specimens has been tested in our
laboratory. 319 respiratory specimens were tested in this preliminary study and
results were compared to smear and culture. Fourteen had a positive culture for
MTB. Among theses samples, smear was positive in 11 cases (78.6%) and TRC process
was positive in 8 cases (57.1%). Overall sensitivity of TRC compared to smear
positive samples is 73%. Theses first results demonstrated that a rapid
identification of MTB was possible (less than 2 processing hours for 14 specimens
and about 1 hour for 1 specimen) in most cases of smear positive samples using
ready to use reagents for real time detection of MTB rRNA in clinical samples.
New pretreatment and extraction reagents kits to increase the stability of the
sputum RNA and the extraction efficiency are now tested in our laboratory.
PMID- 17027193
TI - [Bacterial DNA alteration by plasma generated atomic nitrogen. Real-time PCR
detection contribution].
AB - AIMS: Bacterial sterilization by the technology of plasma in post-discharge shows
a growing interest. The main appeal of this new process resides in its action at
dry and low temperature (60 degrees C). This technology would be therefore useful
for the complex medical equipment, sensitive to the oxidization, humidity and/or
requiring a temperature lower than 60 degrees C. The objective of this survey is
to demonstrate the activity of an atomic flux emanating a plasma of pure
molecular nitrogen on the bacterial DNA: does the plasma of nitrogen damage the
genetic material? MATERIALS AND METHODS: The bacteria tested (Bacillus
stearothermophilus, Staphylococcus aureus MRSA and Helicobacter pylori) are
cultivated on suitable agar, and the bacterial DNA is extracted from every CFU by
the technique of the columns (High Pure PCR Template, Roche). Every quantity of
DNA extracted is diluted in 1 ml pure water. Then, 50 microl of each of these
solutions of DNA are laid down in sterile Nunclon's plates holes, which undergo
an advanced emptiness cycle during 60 minutes. The DNA residues will be then
introduced during 40 minutes in a plasma sterilization surrounding wall
(Plasmalyse), Satelec) where the debit of nitrogen, the pressure and the
temperature are adjusted respectively to 1 L x min(-1), 5 Torrs and 60 degrees C.
The DNA so ''plasmalyse'', is recovered then by aspiration in 500 mul pure water
and processed to undergo an amplification/detection by Real-Time PCR
(LightCycler2.0, Roche). The DNA ''plasmalyse'' will be compared to the intact
DNA control(1), to the DNA control control(2) having undergone the cycle of
emptiness solely, as well as to the DNA control(3) solely heated to 60 degrees C
during 40 min. RESULTS: The amplification curves demonstrated that the only
advanced emptiness and the only heat don't have any activity on the bacterial
DNA. On the other hand, the DNA ''plasmalyse'' shows a deterioration of the
amplified sequences. CONCLUSION: The genomic bacterial DNA, once extracted, is
damaged by the gaseous flux of nitrogen plasma. A new sterilization process of
the medical material will presumably impose itself in medium-term.
PMID- 17027194
TI - Evaluation by Q-RTPCR of the efficacy of ribavirin complexed with beta
cyclodextrin against measles virus in a mouse encephalitis model.
AB - The objective of this work was to study the antiviral activity of ribavirin on
measles encephalitis infection when using cyclodextrins as carriers. The use of
cyclic oligosaccharides can promote the activity of many drugs and the benefit of
the association of ribavirin with beta-cyclodextrin has already been demonstrated
in vitro. Intracranial inoculation of the rodent adapted neurovirulent CAM/RB
strain of measles virus induces encephalitis in CBA/ca mice. The antiviral
activity of the complex ribavirin/beta-cyclodextrin at molar ratio 1:1 has been
evaluated in vivo in the above encephalitis model. CBA/ca mice were treated with
daily intraperitoneal injection of ribavirin (40 mg/kg) with or without beta
cyclodextrin. The viral load in the brain of mice was quantified by real-time
Reverse transcription-Polymerase chain reaction. Treatment of mice by the complex
ribavirin/beta-cyclodextrin (1:1) by intraperitoneal route decreases the viral
load in the brain of 1.1 and 0.7 log(10) Eq copies x mL(-1) compared to
distillated water and ribavirin treatment, respectively. At the same time, free
ribavirin injection shows a negligible difference compared to treatment by
distillated water.
PMID- 17027195
TI - Recent and future therapeutic advances in the management of HIV infection.
AB - Human immunodeficiency virus (HIV) infection is a worldwide pandemic that remains
a major health and socio-epidemiological problem at the beginning of the 21st
century, including in developed countries. In 2006, 10 years after the
introduction of highly active antiretroviral therapy (HAART), therapeutic needs
in HIV are different from what they were a decade ago. Physicians now handle more
than 20 different molecules, all active against HIV virus. However, they still
need safe, tolerable and simple regimens in order to improve patient's compliance
to therapy, as well as more potent drugs in cases of multi-resistant viral
strains. Our understanding of HIV infection and its medical management has
improved and will certainly continue to evolve. We are currently taking benefit
from the elaboration and evaluation of various new therapeutic concepts and
promising future medical approaches based on already 20 years experience in the
field of HIV management, as well as on the rapidly expanding pharmaceutical
development and researches in this domain. Nevertheless, the majority of these
new therapeutic strategies are still to be further evaluated, and their practical
application is awaiting the results of numerous ongoing clinical trials.
PMID- 17027196
TI - [Simultaneous detection by multiplex PCR of atypical bacterial pathogens involved
in infections of respiratory tract. Is it useful for the microbiological
diagnosis of respiratory infections].
AB - The aim was to evaluate the "strategical place" of the new commercial test
Chlamylege (Argene-Biosoft-France) which allows the simultaneous detection in
respiratory samples of Chlamydophila pneumoniae, Mycoplasma pneumoniae and most
Legionella species using a PCR multiplex. 41 patients with an atypical pneumonia
were included, all standard procedures of diagnosis were done and in addition the
chamylege test. A pathogen was identified in 12 patients, an other microorganisms
than the 3 targeted by our study was found in 8 patients. 4 positive PCR were
obtained, 3 with M. pneumoniae and 1 with Legionella pneumophila 1. That means
that for 29 patients no aetiology was found. Among them 23 clearly improved under
antibiotic treatment. Though that PCR multiplex is an attractive test, easy to
perform, sensitive, specific and convenient, we need further studies to approach
the place of this PCR test in the diagnosis of multifaceted atypical pneumonia.
We also need to know if the cost associated with the microbiological diagnosis
(culture, serology, immunofluorescence, urinary antigen test, PCR...) for
atypical pneumonia worth value? An algorithm as to be drawn to determine the
value of intensive microbiological investigation. An other point to discuss, may
be this kind of rapid and multiplex PCR technique could lead to spare the use of
some antibiotics.
PMID- 17027197
TI - Prevalence of agr specificity groups among methicilin resistant Staphylococcus
aureus circulating at Charles Nicolle hospital of Tunis.
AB - Methicillin resistant Staphylococcus aureus (MRSA) is a major human pathogen with
many clinical aspects. In S. aureus, the accessory gene regulator (agr) globally
controls the production of virulence factors. There are four agr groups. Our
study was done to define the agr specificity of MRSA circulating at Charles
Nicolle hospital and to investigate a possible relationship between agr groups
and human disease types. From January 2004 to June 2005, a total of 57 MRSA
isolated from individual hospitalized patients were collected, representing 12%
of the total S. aureus isolates. The isolates were identified by conventional
methods. Methicillin resistance was detected by oxacillin and cefoxitin disks and
confirmed by the amplification of mecA gene by PCR. The agr groups were
identified by multiplex PCR. All the strains were recovered from different wards:
medicine (57.8%) especially from dermatology (56.2%), surgery (28%) and
pediatrics (7%). Cutaneous pus (36.84%) and blood culture (35.08%) represented
the main specimens. The agr groups were distributed as follow nine (15.7%)
belonged to group I, two (3.5%) belonged to group II and 23 (40.3%) belonged to
group III. For 23 strains, the agr group was not identified. A relationship
between agr group and type of disease was observed: agr group III strains were
associated with non invasive infections (P=0.02) and agr group I strains with
invasive infections especially bacteremia (P=0.002).
PMID- 17027198
TI - [Optimisation of retrospective diagnosis of cytomegalovirus congenital infection
from dried blood spots].
AB - Out of the 90% of cytomegalovirus (CMV) congenitally infected children that are
asymptomatic at birth, 5 to 15% will later develop complications, mainly
neurodevelopmental defects and/or deafness. Unfortunately, after the first 2
weeks of life, usual diagnostic techniques for CMV detection (viral culture and
serology) are useless to differentiate congenital infection from post-natal
acquired infection, whereas detection of viral DNA from dried blood spots (DBS;
Guthrie cards), systematically collected from all newborns in the first days of
life, has been described for late diagnosis of CMV congenital infection. The aim
of our study was to choose and optimise a viral DNA extraction method from DBS
and to study if CMV DNA detection is reliable when DBS are stored for 1 year at
room temperature or 2 months at 37 degrees C. 10 reference cards (blood collected
from CMV seronegative newborns (IgG/IgM negative) were "infected" with serial
dilutions of virus and spotted on Guthrie cards) were tested. 3 extraction
methods were evaluated, products of PCR were analyzes by agarose gel
electrophoresis and quantification of CMV from DBS was also performed. Analysis
of the results obtained from reference cards showed higher sensitivity of
phenol/chloroform extraction following treatment with proteinase K, compared to
heat extraction in cell culture medium or extraction with a commercial kit. We
did not observe quantitative loss of viral DNA after 1 year storage at room
temperature. CMV DNA detection from Guthrie cards could become a very useful tool
for retrospective diagnosis of congenital CMV infection when sequelae are
diagnosed in the first years of life. We are pursuing this study with DBS from
congenitally infected children.
PMID- 17027199
TI - Phylogenetic relationships and gene expression pattern of three different
cathepsin L (Ctsl) isoforms in zebrafish: Ctsla is the putative yolk processing
enzyme.
AB - Certain cysteine proteases, such as cathepsin L (Ctsl), have been involved in
yolk processing mechanisms in oocytes and embryos of lower vertebrates. In
zebrafish (Danio rerio), three different ctsl genes, ctsla, ctslb and ctslc, have
been found in the genome, but their pattern of expression, as well as information
on which the encoded enzymes are potentially involved in yolk absorption during
embryogenesis, is unknown. Here, phylogenetic and gene structure analysis
revealed that zebrafish ctsla and ctslb genes are similar, showing a highly
conserved structure in comparison with human ctsl, while ctslc presents different
exon organization together with an earlier evolution. Thus, ctslc appears to be
evolved from a common ancestral ctsl-like gene, possibly through an early
duplication event, whereas ctsla and ctslb may be originated from a second
duplication mechanism. Zebrafish ctsla, ctslb and ctslc also showed different
patterns of mRNA expression during embryogenesis and in adult tissues. While
Ctsla transcripts were accumulated in embryos throughout development and in the
adult ovary, those encoding Ctslb were detected only in embryos around the time
of hatching as previously reported, and those for Ctslc appeared only in larvae
and in some adult tissues, but not in the ovary. In zebrafish and killifish
(Fundulus heteroclitus) embryos, Ctsla mRNA was first detected in blastomers, and
later in development it was localized in cells of the yolk syncytial layer, an
embryonic structure involved in yolk absorption. These data therefore suggested
that Ctsla is most likely the putative protease involved in yolk processing in
fish embryos, while Ctslc seems not to be required during early embryogenesis in
zebrafish.
PMID- 17027200
TI - Introduction for the Gene special issue dedicated to the meeting "Genomic impact
of eukaryotic transposable elements" at Asilomar.
PMID- 17027201
TI - DNA damage and repair capacity by comet assay in lymphocytes of white-collar
active smokers and passive smokers (non- and ex-smokers) at workplace.
AB - The comet assay has been widely used to quantify DNA damage in isolated
lymphocytes from subjects exposed to several environmental or occupational
substances, especially for estimation of oxidative damage in the DNA, which is
well-known to be induced by tobacco smoke. Passive smoking or environmental
tobacco smoke (ETS) has been included among those substances that cause cancer
with sufficient evidence in humans. In this study, we analyzed, by the alkaline
version of comet assay, the lymphocyte DNA damage of white-collar active smokers
and non- and ex-smokers exposed to ETS at the workplace. We investigated basal
DNA damage, DNA oxidation by formamidopyrimidine glycosylase (Fpg), the repair
capacity H2O2-induced DNA damage by kinetics studies and lymphocyte GSH levels,
the major intracellular defense against exogenous oxidative stress imposed by
cigarette smoking. Our results indicated high basal DNA damage with clear
significant correlations with urinary nicotine and cotinine, number of
cigarettes/day, and an inverse significant correlation with GSH cellular content
in active smokers. Significant Fpg-sensitive sites were found in smokers (> 85%),
considerably high but not significant in passive non- and ex-smokers (> 51% and
37%, respectively). The DNA repair capacity had seriously decreased in non
smokers > smokers > ex-smokers, while the same damage was repaired in a short
time in never smokers.
PMID- 17027202
TI - Early detection and treatment of vesicular adenitis in bulls.
AB - The objective of this study was to determine whether early detection and
treatment with tilmicosin would reduce the number of yearling bulls culled due to
vesicular gland disease at the time of their first semen test. Bulls (n=2207) of
15 breeds at 17 performance test stations were examined by transrectal palpation
at 9-12 months of age and assigned to three treatment groups: (1) positive
treated group, receiving subcutaneous injections of tilmicosin every second day
for three treatments (2) positive untreated control group, (3) negative untreated
control group. Transrectal palpation of the glands was done again at a pre-sale
semen test 28-70 d (mean=42.8 d) after the first examination. Semen was evaluated
for the presence of pus and/or leukocytes by light microscopy. The proportion of
bulls with vesiculitis was 4.4% (97/2207). At the pre-sale semen test the number
of bulls with vesiculitis had decreased to 1.3% (29/2207); however, seven of
these were new cases that developed after the first examination. Therefore, there
was a recovery rate of 75/97 (77.3%) in the original group of bulls positive for
vesiculitis. At the pre-sale test, there was no difference in the proportion of
bulls with enlarged glands in the positive treated group (15/66) versus the
positive untreated group (7/31) and no difference in the proportion of bulls with
leukocytes or pus in their semen samples. The results of this experiment did not
indicate any advantage in detection and treatment of vesiculitis before a year on
age due to a high rate of spontaneous recovery.
PMID- 17027203
TI - Changes in the ovarian dynamics and endocrine profiles in goats treated with a
progesterone antagonist during the early luteal phase of the estrous cycle.
AB - The aim of the present study was to determine the physiological role of
endogenous progesterone in the regulation of ovarian dynamics, gonadotropin and
progesterone secretion during the early luteal phase in the goat. Cycling Shiba
goats received subcutaneously a vehicle (control group, n=5) or 50 mg of RU486
(RU486 group, n=4) daily from 1 to 7 days after ovulation (day 0) determined by
transrectal ultrasonography. Ovarian dynamics were monitored by the
ultrasonography and blood samples were collected daily until the subsequent
ovulation for analysis of progesterone, luteinizing hormone (LH) and follicle
stimulating hormone (FSH) secretion. Blood samples were also collected at 10 min
intervals for 6 h on day 3 and day 7 for the analysis of pulsatile patterns of LH
and FSH. The LH pulse frequency was significantly (P<0.05) higher in the RU486
group than in the control group on day 7 (4.8+/-1.1 pulses/6 h versus 1.2+/-0.4
pulses/6 h). The shape of the FSH pulses was unclear on day 3 and day 7 in both
groups and the overall means of FSH concentration for 6 h on day 3 and day 7 were
not significantly different between the RU486 and the control groups. The pattern
of daily FSH concentrations showed a wave-like fluctuation in both groups. There
was no significant difference in the inter-peak intervals of the wave-like
pattern of daily FSH secretion between the RU486 and the control groups (4.1+/
0.6 days versus 4.5+/-0.6 days). The maximum diameter of the largest follicle
that grew from day 1 to day 7 in the RU486 group tended to be greater than that
in control goats (6.4+/-0.8 mm versus 5.0+/-0.8 mm, P=0.050), whereas no
significant difference was detected in the size of the corpus luteum and
progesterone concentrations between the control and RU486 groups on almost all
days during the treatment period. These results indicate that the rise of the
progesterone concentration suppresses the pulsatile LH secretion and follicular
growth, whereas progesterone has no physiological role in the regulation of FSH
secretion and luteal function during the early luteal phase of the estrous cycle
in goats.
PMID- 17027204
TI - Stabilization of protein encapsulated in poly(lactide-co-glycolide) microspheres
by novel viscous S/W/O/W method.
AB - In stabilizing proteins during microsphere fabrication, the viscous solid-in
water-in-oil-in-water (S/W/O/W) method was compared to the conventional multi
emulsion W/O/W and S/O/W method. Solid proteins lyophilized with cyclodextrin
derivatives and polyethylene glycol (PEG) pass through an organic solvent phase
and are then embedded in aqueous microdroplets of first emulsion. Proteins were
stabilized at the water/organic solvent interface by an internal aqueous phase
containing viscous polysaccharides, and then can be safely encapsulated without
degradation. In addition, these microspheres showed a long-term protein release
followed by nearly zero-order kinetics with minimal initial burst. This means
that the viscous S/W/O/W method provides a safe strategy for microsphere
fabrication and has promising properties, involving the preservation of protein
bioactivity, the inhibition of protein denaturation or agglomeration, and long
term protein release.
PMID- 17027205
TI - Doxorubicin skin penetration from monoolein-containing propylene glycol
formulations.
AB - Topical chemotherapy with the antineoplastic doxorubicin (DXR) could be an
alternative to treat skin cancer, however its poor skin penetration often limits
the efficacy of topical formulations. The aim of this work was to study the
effect of monoolein (MO), a penetration enhancer, on the in vitro skin permeation
and retention of DXR. DXR was incorporated in a propylene glycol preparation
containing 0-20% of MO. DXR release rate and topical delivery were evaluated in
vitro using acetate cellulose membrane and porcine skin, respectively, mounted in
a Franz diffusion cell. At 5%, MO did not significantly change DXR release rate,
but MO concentrations larger than 10% decreased almost twice its release. In
vitro skin penetration studies showed that the presence of MO in the propylene
glycol formulations markedly increased DXR presence in the stratum corneum (SC).
At 5%, MO significantly increased the amount of DXR in the SC already in the
first hours, attained a maximum in 6h. Comparing propylene glycol formulations
containing more than 10% MO with that containing 5%, the former took the double
of the time (12h) to reach the same amount of DXR in the skin, result that is in
agreement with in vitro release studies. Interesting, despite the fact that MO
significantly increased the amount of DXR in the SC, drug transdermal delivery
did not change. These findings suggest a cutaneous delivery of DXR that is an
important condition for topical treatment of skin tumors. Further in vivo
experiments can show DXR delivery to deeper skin layers.
PMID- 17027206
TI - A novel multicompartimental system based on aminated poly(vinyl alcohol)
microspheres/succinoylated pullulan microspheres for oral delivery of anionic
drugs.
AB - Poly(vinyl alcohol) (PVA) microspheres were prepared by dispersion reticulation
with glutaraldehyde and further aminated. These microspheres were firstly loaded
with diclofenac (DF) and then entrapped in cellulose acetate butyrate (CAB)
microcapsules by an o/w solvent evaporation technique for intestinal delivery of
drug. The encapsulated PVA microspheres due to their low swelling degree in
intestinal fluids, do not have enough force to produce the disruption of CAB
shell, therefore different amounts of succinoylated pullulan microspheres (SP-Ms)
(exchange capacity up to 5.2 meq/g) were co-encapsulated. The SP-Ms do not swell
in acidic pH, but swell up to 20-times in intestinal fluids causing the rupture
of CAB shell and facilitating the escape of loaded PVA microspheres.
PMID- 17027207
TI - Effect of the melt granulation technique on the dissolution characteristics of
griseofulvin.
AB - This work describes a melt granulation technique to improve the dissolution
characteristics of a poorly water-soluble drug, griseofulvin. Melt granulation
technique is a process by which pharmaceutical powders are efficiently
agglomerated by a meltable binder. The advantage of this technique compared to a
conventional granulation is that no water or organic solvents is needed. Because
there is no drying step, the process is less time consuming and uses less energy
than wet granulation. Granules were prepared in a lab scale high shear mixer,
using a jacket temperature of 60 degrees C and an impeller speed of approximately
20,000 rpm. The effect of drug loading (2.5/5%), binder (PEG 3350/Gelucire
44/14), filler (starch/lactose), and HPMC on the dissolution of griseofulvin was
investigated using a half two level-four factor factorial design. The granules
were characterized using powder XRD, DSC and SEM techniques. A significant
enhancement in the in vitro dissolution profiles of the granules was observed
compared to the pure drug and drug excipient physical mixtures. The factorial
design results indicated that higher drug loading and the presence of HPMC
reduced the extent of dissolution of the drug, whereas, the presence of starch
enhanced the dissolution rate. XRD data confirmed crystalline drug in formulation
matrices. DSC results indicated monotectic mixtures of griseofulvin with PEG in
the granulated formulations. In conclusion, the results of this work suggest that
melt granulation is a useful technique to enhance the dissolution rate of poorly
water-soluble drugs, such as, griseofulvin.
PMID- 17027208
TI - Antispasmodic and relaxant effects of the hidroalcoholic extract of Pimpinella
anisum (Apiaceae) on rat anococcygeus smooth muscle.
AB - The present work describes the mechanisms involved in the muscle relaxant effect
of ethanol:water (40:60, 60:40 and 80:20) aerial parts extracts of Pimpinella
anisum. Three hidroalcoholic extracts in which the proportion of ethanol was 40%
(HA(40%)), 60% (HA(60%)) or 80% (HA(80%)) were tested for activity in the rat
anococcygeus smooth muscle. The three extracts (50 microg/mL) inhibited
acetylcholine-induced contraction. The extract HA(60%) (5-50 microg/mL)
concentration dependently relaxed acetylcholine-pre-contracted tissues (31.55+/
3.56%). Conversely, HA(40%) and HA(80%) did not exert relaxant action. Pre
incubation of the preparations with N(G)-nitro-L-arginine methyl ester (L-NAME,
100 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 3 microM) and
oxyhemoglobin (10 microM) reduced the relaxation induced by HA(60%) (percentage
of relaxation: 6.81+/-1.86%, 13.13+/-5.87% and 2.12+/-1.46%, respectively).
Neither indomethacin (10 microM) nor tetraethylammonium (1 mM) affected the
relaxation induced by HA(60%). Incubation of the tissues with L-NAME
significantly enhanced the maximal contraction induced by acetylcholine,
indicating an inhibitory role for NO in the modulation of the contractile
response of anococcygeus smooth muscle to acetylcholine. However, simultaneous
addition of L-NAME and HA(60%) resulted in an effect similar to that observed
with L-NAME alone, further confirming the observation that Pimpinella anisum acts
by realizing NO. Additionally, HA(60%) did not alter CaCl(2)-induced contraction.
Collectively, our results provide functional evidence that the effects elicited
by the hidroalcoholic extract of Pimpinella anisum involve the participation of
NO and subsequent activation of the NO-cGMP pathway. The relaxant action
displayed by Pimpinella anisum justifies its use in the folk medicine as an
antispasmodic agent.
PMID- 17027209
TI - Using tibia fragments from South Africans of European descent to estimate maximum
tibia length and stature.
AB - Intact long limb bones have been used in the derivation of regression equations
for stature assessment in different population groups. Since intact long bones
are not always present for analyses in forensic cases, it has become necessary to
derive regression equations for the estimation of stature from the fragments of
these bones which are obtained in forensic and archaeological cases. Regression
equations have been derived for stature estimation from fragments of the tibia.
Since these equations are population specific, it was the aim of this study to
derive similar equations for estimation of stature and maximum tibia length from
measurements of different fragments of tibia of South Africans of European
descent. Analyses were based on a sample of 50 male and 50 female complete
skeletons of adult South Africans of European descent. Total skeletal height for
the individual skeletons was measured using the Fully's (anatomical) method. Six
variables were measured on the tibia which included the medial tibial condyle
lengths and breadths, lateral tibial condyle lengths and breadths, proximal
breadth and distal breadth. Univariate and multivariate regression equations were
formulated for estimation of total skeletal height (and subsequent estimation of
living stature) and maximum tibial length from measurements of the tibia. The
standard errors of estimate for the equations were higher than those obtained for
intact long bones which when present in forensic cases should be used for stature
estimation. In the absence of intact long bones, the equations derived from the
present study can provide a reliable estimate of skeletal height and living
stature.
PMID- 17027211
TI - Motor and reflex testing in GM1-gangliosidosis model mice.
AB - A large number of genetic disease model mice have been produced by genetic
engineering. However, phenotypic analysis is not sufficient, particularly for
brain dysfunction in neurogenetic diseases. We tried to develop a new assessment
system mainly for motor and reflex functions in G(M1)-gangliosidosis model mice.
Two genetically engineered model mouse strains were used for this study: the beta
galactosidase-deficient knockout mouse representing infantile G(M1)
gangliosidosis (severe form), and transgenic mouse representing juvenile G(M1)
gangliosidosis (mild form). We modified human child neurology techniques, and
selected eleven tests for motor assessment and reflex testing. The test results
were scored in four grades: 0 (normal), 1 (slightly abnormal), 2 (moderately
abnormal), and 3 (severely abnormal). Both disease model mouse strains showed
high scores even at the apparently pre-symptomatic stage of the disease,
particularly with abnormal tail and hind limb postures. Individual and total test
scores were well correlated with the progression of the disease. This method is
simple, quick, and reproducible. The testing is sensitive enough to detect early
neurological abnormalities, and will be useful for monitoring the natural
clinical course and effect of therapeutic experiments in various neurogenetic
disease model mice, such as chemical chaperone therapy for G(M1)-gangliosidosis
model mice.
PMID- 17027212
TI - [Observance of antiretroviral treatments: African specificities].
AB - Since the Durban conference in 2000, the initiatives of access to antiretroviral
therapy (ART) have expanded in sub-Saharan Africa. It is of high interest to
monitor observance to HAART, in a context of increasing ART use, a rapid increase
of patients under HAART, and the sociocultural specificities in Africa. In sub
Saharan Africa the concept of disease without cure does not exist and a disease
always has or is attributed an external cause. Optimizing observance is a key
element for the success of implementation programs for which we recommend a light
monitoring to follow-up patients and the use of first line and effective
antiretroviral drugs, with a low genetic barrier (efavirenz, nevirapine). The
consequences of non-adherence are extremely negative for a patient in Africa, for
whom we have few assessment tools and a limited number of ART. Improvement of
adherence requires the involvement of all health care actors including
traditional healers.
PMID- 17027213
TI - [Impact of antibiotic use and prescribing policy in a Tunisian intensive care
unit].
AB - OBJECTIVE: The aim of this study was to assess the efficacy of local antibiotic
policy in a Tunisian ICU. The predefined primary efficacy objectives were the
decrease of antibiotic consumption, reduction of inappropriate antibiotic (ATB)
use and antimicrobial resistance. DESIGN: This prospective intervention study
lasted from January 2002 to December 2004. In the first study period or the
baseline phase (from January to December 2002) we focused on physician education
for ATB prescription practice. The second period concerned intervention (control
of all ATB use). RESULTS: The number of infection episodes significantly
decreased from 2002 to 2004; 198 infection episodes in 2002 (1.63+/-1.15
episodes/patient) versus 124 in 2003 (1.22+/-0.93) (P<0.0008) versus 121 in 2004
(1.23+/-0.8) (P1<0.0008). The number of ATB/prescription also significantly
decreased from 1.85+/-1.3 in 2002 to 1.5+/-0.9 in 2003 (P=0.02) and 1.5+/-1.4 in
2004 (P1=0.05). Appropriateness of antibiotherapy improved during the
intervention period: 65% in 2002 versus 86% in 2003 (P=0.0003) and 81% in 2004
(P1=0.02). The length of antibiotherapy in survivors was considerably reduced:
14.1+/-2.9 days in 2002 versus 11.9+/-1.2 days in 2003 (P<10(-5)) and 10.9+/-2.5
days in 2004 (P1<10(-5)) with a significant reduction of antibiotherapy cost and
length of stay (20.4+/-9 days in 2002 versus 18.3+/-6 days in 2003 and 16.9+/-8
days in 2004; P=0.05; P1=0.02). There was a significant decrease of carbapenem
resistant Enterobacteriaceae esbeta, Pseudomonas aeruginosa and Acinetobacter
baumannii.
PMID- 17027214
TI - [A case of severe community acquired pneumonia and non-respiratory illness
induced by Influenza A].
AB - BACKGROUND: Severe community acquired pneumonia is a common cause of acute
respiratory failure. The influenza virus itself can cause a severe pneumonia and
non-respiratory illness. CASE REPORT: A physician developed an acute respiratory
failure associated with hemolytic anemia, acute renal failure, and myocarditis.
Influenza A infection was diagnosed by screening for antibodies (complement
fixation, ELISA Ig A). DISCUSSION: Fulminant influenza pneumonia is a rare
clinical presentation of influenza infection and usually has a severe clinical
course. Influenza infection is also associated with myositis, myocarditis, acute
renal failure, encephalopathy, and hemolytic anemia. Rapid laboratary diagnosis
can be made by PCR or immunofluorescence applied directly to respiratory
specimens. Antiviral treatment did not prove its efficacy in fulminant Influenza.
This case report is an opportunity to stress the importance of seroprophylaxis by
parenteral vaccination in exposed occupations.
PMID- 17027215
TI - [Rhinocerebral mucormycosis: A case report].
AB - Mucormycosis is a rare and acute fungal infection which is frequently lethal,
usually observed in non-controlled diabetic patients. The infection usually
begins in the nose but it can invade the lung, the digestive tract, and the skin.
Rhinocerebral mucormycosis accounts for 40 to 49% of mucormycosis cases. We
report the case of a 53-year-old diabetic man, with chronic renal failure,
presenting with rhinocerebral mucormycosis. Our patient was treated by an
association of amphotericin B and surgical debridement. This observation provides
on opportunity to recall clinical, histopathological, and therapeutic aspects of
rhinocerebral mucormycosis.
PMID- 17027216
TI - [Human babesiosis].
AB - Babesia is one of the most ubiquitous and widespread blood parasite in the world
based on numbers and distribution of species in animals. The clinical
presentation may vary according to the incriminated species. In some states of
the USA this kind of infection is endemic; the number of cases reported in Europe
is inferior but more life-threatening. A better understanding of parasite
specificities such as cycle and pathogenicity allowed to suggest treatment
guidelines adapted to the different clinical and microbiological situations.
PMID- 17027217
TI - [Legionnaire's disease complicated by acute renal failure due to rhabdomyolosis:
a case report].
AB - The infectious origin of non-traumatic rhabdomyolysis is rare (5% of cases). An
elevated muscle enzyme level is often reported in the legionnaire's disease. We
report the case of a 39-year-old male, with no previous medical history, admitted
for renal failure (creatininemia=977 micromol/l) secondary to rhabdomyolysis and
a twelve-day history of infectious syndrome with pneumonia in the left base.
Legionella pneumophila was considered responsible for these symptoms because of a
positive serology. The other microbial assessments were negative. After
rehydration and three weeks of antibiotics, the outcome was favorable: the renal
failure resolved completely and the muscle enzyme level returned to normal.
PMID- 17027218
TI - [Role of antiviral drugs in containing pandemic influenza. Contribution of recent
modelling exercises synthesis prepared by the InVS/Inserm "epidemiology" group -
November 2005].
AB - The growing threat of influenza pandemic has lead many countries to stockpile
specific antiviral drugs, mainly oseltamivir, as it can be used both for
prophylaxis and therapy. Several recently published studies, based on
mathematical modelling, have assessed the impact of a large scale use of this
drug to contain an emerging pandemic, slow its spread within a country or reduce
its epidemiological impact. They conclude that ring antiviral prophylaxis around
the first cases, combined with social distancing measures, may halt a nascent
pandemic, if the human-to-human transmissibility of the virus is limited and the
control measures implemented promptly and with a high coverage. In case of
failure, these same strategies could delay the spread of the virus within a
country. The use of influenza antiviral drugs would reduce the burden of disease
and even the clinical attack rate, under the assumption of a shorter infectious
period for treated patients. These studies are in favour of stockpiling influenza
antiviral drugs, at least to cover the curative needs and, even better, to
contribute to the global effort to contain an emergent pandemic and to allow an
intervention around the first chains of indigenous transmission in a country,
thus slowing the virus spread. These results are based on the hypothesis of the
effectiveness of oseltamivir on the pandemic virus and confirm the critical
importance of a sensitive and reactive surveillance.
PMID- 17027219
TI - [Optimal vancomycin serum level in Staphylococcus aureus infections?].
AB - Vancomycin is the cornerstone of therapy against methicillin-resistant
Staphylococus aureus in both community and nosocomial-acquired infections.
Because vancomycin is a concentration-independent or time-dependant antibiotic,
most clinicians have abandoned the routine practice of determining peak serum
concentrations to rely solely on monitoring serum concentrations. The so-called
therapeutic range most often quoted for vancomycin was assessed for through serum
concentrations of 5-10 mg/l. But prolonged exposure to serum concentration close
to the MIC is associated with the emergence of resistance. More recent guidelines
recommended vancomycin in concentrations of 15-20 mg/l for the treatment of
severe Staphylococcus infections or in situations where vancomycin penetration is
poor. However, because of the great variability of vancomycin MIC(S) (0,12-4
mg/l) of susceptible Staphylococcus strains, guidelines should recommend through
serum concentrations of 5-10 times the MIC.
PMID- 17027220
TI - Alkalibacillus halophilus sp. nov., a new halophilic species isolated from
hypersaline soil in Xin-Jiang province, China.
AB - A halophilic, Gram-positive, spore-forming motile Bacillus-like strain YIM
012(T), was isolated from one of the hypersaline soil samples collected in Xin
jiang province, China. Its optimum growth occurred at 10-20% of NaCl
concentration (w/v), pH 7.0-8.0. Phylogenetic analysis based on 16S rRNA gene
sequences revealed that strain YIM 012(T) is a member of the genus of
Alkalibacillus, which is well supported by its chemotaxonomic and molecular
characteristics. Based on its phenotypic evidence and genotypic data,
Alkalibacillus halophilus sp. nov. was proposed and strain YIM 012(T) (=DSM
17369(T)=KCTC 3990(T)) was assigned as the type strain of the novel species.
PMID- 17027221
TI - The extent and breadth of benefits from participating in chronic disease self
management courses: a national patient-reported outcomes survey.
AB - OBJECTIVE: To quantify the benefits that people receive from participating in
self-management courses and identify subgroups that benefit most. METHODS: People
with a wide range of chronic conditions attending self-management courses (N =
1341 individuals) were administered the Health Education Impact Questionnaire
(heiQ). Baseline and follow-up data were collected resulting in 842 complete
responses. Outcomes were categorized as substantial improvement (effect size, ES
> or = 0.5), minimal/no change (ES -0.49 to 0.49) and substantial decline (ES <
or = -0.5). RESULTS: On average, one third of participants reported substantial
benefits at the end of a course and this ranged from 49% in the heiQ subscale
Skill and technique acquisition to 27% in the heiQ subscale Health service
navigation. Stratification by gender, age and education showed that younger
participants were more likely to benefit, particularly young women. No further
subgroup differences were observed. CONCLUSION: While the well-being of people
with chronic diseases tends to decline, about one third of participants from a
wide range of backgrounds show substantial improvements in a range of skills that
enable them to self-manage. PRACTICE IMPLICATIONS: These data support the
application of self-management courses indicating that they are a useful adjunct
to usual care for a modest proportion of attendees.
PMID- 17027223
TI - Exhaustive genotyping of the interferon alpha receptor 1 (IFNAR1) gene and
association of an IFNAR1 protein variant with AIDS progression or susceptibility
to HIV-1 infection in a French AIDS cohort.
AB - We have undertaken a systematic genomic approach in order to explore the role of
the interferon alpha (IFN-alpha) pathway in AIDS disease development. As it is
very difficult to genotype the IFN-alpha gene itself since it has many pseudo
genes, we have focused our interest on the genetic polymorphisms of the IFN-alpha
receptor 1 (IFNAR1). We genotyped the Genetics of Resistance to Immunodeficiency
Virus (GRIV) cohort composed of patients with extreme profiles of progression to
AIDS, slow progressors (SP) and rapid progressors (RP), as well as seronegative
controls (CTR). We identified 19 single nucleotide polymorphisms (SNPs) with a
minor allele frequency (MAF) greater than 1% among which two were newly
characterized by our study. We found putative associations with AIDS disease
development for four SNP alleles and for three haplotypes. The most interesting
signals were found for two SNPs in linkage disequilibrium, the SNP IFNAR1_18339
corresponding to a Val168Leu mutation in the extracellular domain of the protein
and the intronic SNP, IFNAR1_30127. The intronic SNP IFNAR1_30127 yielded a
strong signal both when comparing SP with CTR (P=0.002) and RP with CTR (P=0.005)
while IFNAR1_18339 yielded a smaller signal because less patients were analyzed;
these SNPs could thus be involved in AIDS progression or in susceptibility to
human immunodeficiency virus 1 (HIV-1) infection. Interestingly, two independent
studies have previously pointed out the SNP IFNAR1_18339 in susceptibility to
multiple sclerosis and to malaria. This is the first work investigating the
polymorphisms of the IFNAR1 gene in AIDS. Our results which point out a possible
role for the IFN-alpha pathway in susceptibility to HIV-1 infection or
progression to AIDS need a necessary confirmation by genomic studies in other
AIDS cohorts.
PMID- 17027222
TI - [Paracervical block in obstetrics].
AB - OBJECTIVE: To review the most recent and relevant issues concerning paracervical
block in obstetrics since 1975 when Jagerhorn described the superficial technique
that has become a standard. DATA SOURCES: Extraction from Pubmed database of
articles issued from 1975 to 2005. DATA SELECTION: The collected articles were
selected on the basis of the use of the superficial injection method. The more
recent data were selected. The keywords were: paracervical, labour, childbirth,
and neonate. DATA SYNTHESIS: Paracervical block (PCB) is routinely used over the
world despite the risk of foetal bradycardia. Bradycardia occurring immediately
after the performance of block is short lasting. The reports of few cases of
foetal or neonatal deaths have caused many physicians to question its safety. The
incidence of bradycardia has dramatically decreased (less than 10%) due to the
Jagerhorn superficial injection method. In case of healthy neonate the occurrence
of bradycardia is harmless but its mechanism is still imprecise. The intensity an
duration of analgesia is poor in comparison with epidural anaesthesia. PCB is a
viable alternative to epidural in selected cases.
PMID- 17027224
TI - Characterization of multipotent cells from human adult hair follicles.
AB - Recent works demonstrated the presence of a multipotent epithelial cell
population in the bulge region of adult human hair follicles. These cells can be
cultured in vitro, thus leading to the preparation of dermal-epidermal
substitutes which are applicable in the treatment of burns and ulcers. We
evaluated the main marker expression in cells obtained from stripped human hair
follicles. A pool of hair follicles were incubated at 37 degrees C and 5% CO(2)
in a growth medium. The cells were then labelled with antibodies (anti-CD34, anti
CD38, anti-CD45, anti-CD90, anti-CD133, anti-CD146) and analysed by cytometry. We
also used hair follicles for immunohistochemical studies, employing antibodies
such as CD34, Actin Smooth Muscle, Filaggrin, Desmin, Vimentin, Glial Fibrillary
Acidic Protein, Ki-67, PanCytokeratin, CK15, CK19. The cytometry results revealed
that a part of bulge cells were CD34+ (1-2%). CD34+ population comprises both
large, CD45-, CD133-, CD146- cells and small, CD45+, CD133+, CD146+ cells. Thus,
a part of CD34+ cells present a mature endothelial marker (CD146). An expression
of the proliferation marker Ki-67 and the stem cell marker CD34 is present in the
follicle bulge region. In conclusion, we observed that the stripped hair follicle
has the same multipotent cell population as adult and fetal scalp hair follicles.
PMID- 17027226
TI - Cognitive conflict without explicit conflict monitoring in a dynamical agent.
AB - We examine mechanisms for resolving cognitive conflict in an embodied, situated,
and dynamic agent, developed through an evolutionary learning process. The agent
was required to solve problems of response conflict in a dual-target "catching"
task, focusing response on one of the targets while ignoring the other. Conflict
in the agent was revealed at the behavioral level in terms of increased latencies
to the second target. This behavioral interference was correlated to peak
violations of the network's stable state equation. At the level of the agent's
neural network, peak violations were also correlated to periods of disagreement
in source inputs to the agent's motor effectors. Despite observing conflict at
these numerous levels, we did not find any explicit conflict monitoring
mechanisms within the agent. We instead found evidence of a distributed conflict
management system, characterized by competitive sources within the network. In
contrast to the conflict monitoring hypothesis [Botvinick, M. M., Braver, T. S.,
Barch, D. M., Carter, C. S., & Cohen, J. D. (2001). Conflict monitoring and
cognitive control. Psychological Review, 108(3), 624-652], this agent
demonstrates that resolution of cognitive conflict does not require explicit
conflict monitoring. We consider the implications of our results for the conflict
monitoring hypothesis.
PMID- 17027225
TI - Selective attention through phase relationship of excitatory and inhibitory input
synchrony in a model cortical neuron.
AB - Neurons in area V2 and V4 exhibit stimulus specific tuning to single stimuli, and
respond at intermediate firing rates when presented with two differentially
preferred stimuli ('pair response'). Selective attention to one of the two
stimuli causes the neuron's firing rate to shift from the intermediate pair
response towards the response to the attended stimulus as if it were presented
alone. Attention to single stimuli reduces the response threshold of the neuron
and increases spike synchronization at gamma frequencies. The intrinsic and
network mechanisms underlying these phenomena were investigated in a multi
compartmental biophysical model of a reconstructed cat V4 neuron. Differential
stimulus preference was generated through a greater ratio of excitatory to
inhibitory synapses projecting from one of two input V2 populations. Feedforward
inhibition and synaptic depression dynamics were critical to generating the
intermediate pair response. Neuronal gain effects were simulated using gamma
frequency range correlations in the feedforward excitatory and inhibitory inputs
to the V4 neuron. For single preferred stimulus presentations, correlations
within the inhibitory population out of phase with correlations within the
excitatory input significantly reduced the response threshold of the V4 neuron.
The pair response to simultaneously active preferred and non-preferred V2
populations could also undergo an increase or decrease in gain via the same
mechanism, where correlations in feedforward inhibition are out of phase with
gamma band correlations within the excitatory input corresponding to the attended
stimulus. The results of this model predict that top-down attention may bias the
V4 neuron's response using an inhibitory correlation phase shift mechanism.
PMID- 17027227
TI - The N-terminal SH2 domain of the tyrosine phosphatase, SHP-2, is essential for
Jak2-dependent signaling via the angiotensin II type AT1 receptor.
AB - Previous work has suggested that the protein tyrosine phosphatase, SHP-2, may act
to facilitate angiotensin II (Ang II)-mediated, Jak2-dependent signaling.
However, the mechanisms by which this occurs are not known. Here, Ang II
mediated, Jak2-dependent signaling was analyzed in a fibroblast cell line lacking
the N-terminal, SH2 domain of SHP-2 (SHP-2(Delta46-110)). While the SHP-2(Delta46
110) cells were capable of activating Jak2 tyrosine kinase, they were unable to
facilitate AT1 receptor/Jak2 co-association, STAT activation and subsequent Ang
II-mediated gene transcription when compared to wild type control cells. These
data therefore suggested that the N-terminal SH2 domain of SHP-2 was acting to
recruit Jak2 to the AT1 receptor signaling complex. We found that the N-terminal
SH2 domain of SHP-2 binds Jak2 predominantly, but not exclusively at tyrosine
201. Mass spectrometry analysis confirmed that this tyrosine residue is in fact
phosphorylated. When this tyrosine was converted to phenylalanine, the ability of
Jak2 to activate subsequent downstream signaling events was reduced. In summary,
we have identified a novel site of Jak2 tyrosine autophosphorylation; namely,
tyrosine 201. Our data suggest that the N-terminal SH2 domain of SHP-2 binds this
amino acid residue. The functional consequence of this interaction is to recruit
Jak2 to the AT1 receptor signaling complex and in turn promote downstream Jak2
dependent signaling.
PMID- 17027228
TI - Wnt-3a utilizes a novel low dose and rapid pathway that does not require casein
kinase 1-mediated phosphorylation of Dvl to activate beta-catenin.
AB - The current view of canonical Wnt signalling is that following Wnt binding to its
receptors (Frizzled-Lrp5/6), dishevelled (Dvl) becomes hyperphosphorylated, and
the signal is transduced to the APC-GSK3beta-axin-beta-catenin multiprotein
complex, which subsequently dissociates. As a result beta-catenin is not
phosphorylated, escapes proteosomal degradation and activates its target genes
after translocation to the nucleus. Here, we analyzed the importance of the Wnt
3a-induced phosphorylation and shift in electrophoretic migration of Dvl (PS-Dvl)
for the activation of beta-catenin. Analysis of Wnt-3a time- and dose-responses
in a dopaminergic cell line showed that beta-catenin is activated rapidly (within
minutes) and at a low dose of Wnt-3a (1 ng/ml). Surprisingly, PS-Dvl appeared
only after 30 min and at greater doses (> or =20 ng/ml) of Wnt-3a. Moreover, we
found that a casein kinase 1 inhibitor (D4476) or siRNA for casein kinase 1
delta/epsilon (CK1delta/epsilon) blocked the Wnt-3a-induced PS-Dvl.
Interestingly, CK1 inhibition or siRNA for CK1delta/epsilon did not ablate the
activation of beta-catenin by Wnt-3a, indicating that there is a PS-Dvl
independent path to activate beta-catenin. The increase in beta-catenin
activation by Wnt-3a (PS-Dvl-dependent or -independent) were blocked by Dickkopf1
(Dkk1), suggesting that the effect of Wnt-3a is in both cases mediated by Lrp5/6
receptors. Thus, our results show that Wnt-3a rapidly induce a partial activation
of beta-catenin in the absence of PS-Dvl at low doses, while at high doses induce
a full activation of beta-catenin in a PS-Dvl-dependent manner.
PMID- 17027230
TI - Longitudinal study of body composition changes associated with weight change and
physical activity.
AB - OBJECTIVE: Weight changes result in fat-free mass (FFM) and body fat (BF)
changes. This study determined FFM and BF changes after weight gain or loss and
whether these changes differ by gender, physical activity, and age. METHODS:
Healthy volunteers, recruited between 1991 and 2003, were followed for 1 y (n =
400) or 3 y (n = 305). Active subjects performed >3 h of physical activity of >
or =4.0 metabolic equivalents/wk, sedentary subjects performed <3 h/wk. Body
weight and body composition by bioelectrical impedance analysis were determined
at year 0, 1, or 3. RESULTS: At years 1 and 3, FFM and BF decreased with weight
loss and increased with weight gain. BF was more sensitive (P < 0.03) to weight
change than FFM. Compared to weight-stable individuals at year 1, weight gains of
1.0-1.9, 2.0-2.9, and > or =3.0 kg changed FFM by -0.04 (P = 0.90), +0.48 (P =
0.15), and +1.39 kg and BF by +1.35, +1.87, and +3.09 kg, respectively (all P <
0.001). Comparable FFM and BF decreases were observed for weight losses (FFM
0.28 kg, P = 0.38; -0.75 kg, P = 0.04; -1.51 kg, P < 0.001; BF -1.01 kg, P <
0.01; -1.55 kg, P = 0.01; -3.13 kg, P < 0.001). These relations were similar
across gender and age strata. At year 1, active individuals were less likely to
gain BF with weight gain and more likely to lose BF with weight loss than were
sedentary individuals, except for weight losses >3 kg. At year 3, the association
between body weight and FFM and BF change was similar between active and
sedentary individuals. CONCLUSION: Greater weight changes (>3 kg) are necessary
for weight change to have a significant effect on FFM than to have an effect on
BF.
PMID- 17027231
TI - Allicin, a major component of garlic, inhibits apoptosis of macrophage in a
depleted nutritional state.
AB - OBJECTIVE: Allicin is believed to be the main component responsible for the
biological activity of garlic. The regulation of cell death might have
therapeutic potential in many diseases, and previous studies have demonstrated
that allicin stimulates the functional activity of macrophages. Therefore, this
study examined the effects of allicin on the apoptosis of macrophages induced by
serum- and amino acid-free culture. METHODS: The apoptosis of peritoneal
macrophages was examined after pretreating them with allicin and incubating them
in a depleted nutritional state. The rate of apoptosis was determined using
propidium iodide staining analysis using flow cytometry, DNA fragmentation, and a
caspase-3 assay. Western blot analysis was used to examine the changes in the pro
or antiapoptotic protein expression levels. RESULTS: DNA fragmentation and
propidium iodide staining analyses revealed that allicin decreased the
malnutrition-induced apoptosis of macrophages. The level of Bax expression, the
amount of cytochrome-c released from the mitochondria, and the caspase-3 activity
were also lower in the allicin-treated macrophages than in the untreated
macrophages in a depleted nutritional state. Moreover, the MEK (mitogen-activated
protein kinase/extracellular signal-regulated kinase-kinase) inhibitor suppressed
the allicin-induced inhibition of apoptosis in a depleted nutritional state and
allicin increased the level of ERK1/2 phosphorylation. CONCLUSION: Allicin
inhibits the apoptosis of macrophages in a depleted nutritional state through the
MEK/extracellular signal-regulated kinase pathway.
PMID- 17027229
TI - Low-carbohydrate and high-fat intake among adult patients with poorly controlled
type 2 diabetes mellitus.
AB - OBJECTIVE: This study examined baseline dietary intake, body weight, and
physiologic status in patients enrolled in a dietary intervention for type 2
diabetes mellitus (T2DM). METHODS: Dietary, physiologic, and demographic
information were collected at baseline from 40 adult patients with poorly
controlled T2DM (glycosylated hemoglobin >7%) who participated in a clinical
trial at an academic medical center in Worcester, Massachusetts, USA. RESULTS:
The average age at enrollment was 53.5 y (SD 8.4), average body mass index was
35.48 kg/m(2) (SD 7.0), and glycosylated hemoglobin was 8.3% (SD 1.2).
Participants were predominantly white, married, and employed full time. Forty
eight percent were men. Seventy-eight percent had hyperlipidemia, and 68% had
hypertension. Reported baseline daily average energy intake was 1778 kcal (SD
814), daily carbohydrate was 159 g (SD 71.5), and dietary fiber was 11.4 g (SD
5.2). The dietary composition was 35% carbohydrate, 45% fat (15% saturated fat),
and 20% protein. The American Diabetes Association (ADA) guidelines recommends 45
65% of energy from carbohydrate, 20-35% from fat (<7% saturated), and 20% from
protein. CONCLUSION: These patients reported a low-carbohydrate, low-fiber, high
fat (especially saturated) diet, although they stated they are not following any
of the popular low-carbohydrate diets. Patients with T2DM may find the current
trend toward reducing weight through low-carbohydrate diets attractive for
control of blood glucose, despite ADA recommendations. This dietary pattern may
represent a popular trend that extends beyond our particular study and, if so,
has serious cardiovascular implications in this vulnerable population of T2DM
patients.
PMID- 17027232
TI - Effect of fish oil pretreatment on isoproterenol-induced changes in myocardial
membrane phospholipids.
AB - OBJECTIVE: In the present study, the protective effect of fish oil treatment on
the fatty acid composition in isoproterenol (IPH)-induced myocardial infarction
was studied in male albino Wistar rats. METHODS: Rats were injected for 2
consecutive days with IPH (60 mg/kg body weight) at 24-h intervals to induce
myocardial infarction. Fish oil was administered orally at a dose of 0.05 mL/d
for 45 d, after which serum and heart tissue were assayed for lipid profile,
lipoprotein changes, and myocardial membrane phospholipid fatty acid composition.
RESULTS: Biochemical assessment of myocardial infarction was done by measuring
the activities of creatinine kinase and lactate dehydrogenase, which were
significantly elevated in the rats administered with IPH. Further, the
administration of IPH modified the fatty acid composition and analysis of fatty
acids showed there was an increase in the omega-3/omega-6 ratio in phospholipid
pool. In addition, increased levels of total cholesterol, free cholesterol, ester
cholesterol, phospholipids, triacylglycerols and free fatty acid was observed in
serum and heart tissue of IPH-induced rats. The fish oil treatment for a period
of 45 d decreased the levels of cardiac markers (creatinine kinase and lactate
dehydrogenase) and reversed the biochemical lesions induced by IPH. CONCLUSION:
Our study suggests that fish oil treatment has a hypolipidemic effect and has
potential use in the treatment of myocardial infarction.
PMID- 17027233
TI - Konjac acts as a natural laxative by increasing stool bulk and improving colonic
ecology in healthy adults.
AB - OBJECTIVE: Konjac glucomannan (KGM) has been shown to relieve constipation, which
could be associated with increased stool bulk and improved colonic ecology.
METHODS: This placebo-controlled study consisted of a 21-d placebo period, a 7-d
adaptation period when volunteers consumed KGM progressively, and a 21-d KGM
supplemented period (1.5 g/meal, 4.5 g/d). Eight healthy adults consumed 7-d
cycle menus of typical low-fiber Chinese food throughout the study. The
gastrointestinal response was monitored daily. Stools were fully collected on
days 15 to 21 of placebo and KGM periods to determine the fecal mass, components,
microflora, and short-chain fatty acid contents. RESULTS: The KGM supplement
significantly increased the mean defecation frequency (number/day), wet stool
weight, and dry stool weight (g/d) by approximately 27.0% (P < 0.05), 30.2% (P <
0.05), and 21.7% (P < 0.05), respectively. The dry fecal mass increased mainly in
the plant and soluble material, whereas bacterial mass tended to increase from
12.9 +/- 1.6 to 13.6 +/- 2.7 g/d (P > 0.05). However, KGM significantly promoted
the fecal concentrations (log counts/g wet feces) of lactobacilli (P < 0.05) and
total bacteria (P < 0.05), and promoted the daily output (log counts per day) of
bifidobacteria (P < 0.05), lactobacilli (P < 0.05), and total bacteria (P < 0.05)
as evaluated by the fluorescence in situ hybridization method. KGM supplement
also promoted colonic fermentation as shown in the decreased fecal pH (P < 0.05)
and increased fecal short-chain fatty acid concentrations (P < 0.05). CONCLUSION:
Supplementation of KGM into a low-fiber diet promoted the defecation frequency in
healthy adults, possibly by increasing the stool bulk, thus promoting the growth
of lactic acid bacteria and colonic fermentation.
PMID- 17027234
TI - Resonance frequency measurements of implant stability in the dog mandible:
experimental comparison with histomorphometric data.
AB - The aim of the present study was to test the hypothesis that measurements of
implant stability using resonance frequency analysis (RFA) correlate with
histomorphometric data of bone anchorage. Ten adult female foxhounds received a
total of 80 implants in their mandibles 3 months after removal of all premolar
teeth. At the time of implant placement, torque required for bone tapping was
registered as a measure of bone density and immediately after placement implant
stability was assessed using RFA. RFA measurements were repeated at the time of
implant retrieval after 1 month (5 dogs) and 3 months (5 dogs). Peri-implant bone
regeneration was assessed histomorphometrically by measuring bone-implant contact
(BIC) and the volume density of the newly formed peri-implant bone (BVD). RFA
values at the time of implant placement did not correlate with the torque
required to tap the bone for implant placement. After 1 and 3 months, RFA values
were significantly increased compared with baseline values. BIC and BVD, however,
had increased significantly during this interval. There was no correlation
between bone-implant contact and RFA values nor between peri-implant bone density
and RFA values. Thus, the hypothesis could not be verified. It is concluded that
the validity of the individual measurement of implant stability using RFA should
be considered with caution.
PMID- 17027235
TI - Osseointegration of oxidized and turned implants in circumferential bone defects
with and without adjunctive therapies: an experimental study on BMP-2 and
autogenous bone graft in the dog mandible.
AB - The aim of the study was to compare the integration and implant stability of
turned and oxidized titanium implants when placed in experimental bone defects
with autogenous bone graft, BMP-2 or without adjunctive therapy. Four defects
were prepared on each side of the mandible of 12 mongrel dogs five months after
tooth extractions. Implants with turned and oxidized surfaces were placed in the
defects. The circumferential gaps were filled with either autogenous bone grafts,
a BMP-allogeneic dog mixture in a thermoplastic carrier, carrier alone or left
without any treatment (control). There were no statistically significant
differences between control and treated sites, neither for turned nor for
oxidized implants with regard to histomorphometric measurements in ground
sections and to implant stability as measured with resonance frequency analysis
(RFA) after 4 and 12 weeks of healing. However, oxidized implants showed a
significantly higher stability after 4 weeks and a tendency (p < 0.1) of that
after 12 weeks. Histomorphometry showed more bone contacts for oxidized than for
turned implants. It is concluded that oxidized implants gain stability more
rapidly and integrate with more bone contacts than implants with a turned surface
when placed in bone defects.
PMID- 17027236
TI - MRI abnormalities of the hippocampus and cavum septi pellucidi in females with
schizotypal personality disorder.
AB - OBJECTIVE: This study examined MRI hippocampal volume and cavum septi pellucidi
(CSP) in female subjects with schizotypal personality disorder (SPD) and
comparison subjects. METHOD: MRI was performed on 20 SPD and 29 comparison
subjects with delineation of left and right hippocampi. Number of slices
containing the CSP was counted. Subjects were given a working memory task, the
Delayed Alternation task and other measures of working memory including the
Wechsler Memory Test-Revised and the California Verbal Learning Test. Clinical
measures were derived from the SCID-II. RESULTS: SPD females evinced bilaterally
smaller hippocampal volumes compared with non-psychiatric female subjects (15.1%
on left, 15.7% on right). Additionally, SPD subjects showed statistically
significantly more slices containing CSP, and a trend level difference when large
CSP was defined as four or more slices (20% vs. 6.9%). SPD subjects demonstrated
more errors, more perseverations, and a trend toward more failure to maintain set
on the Delayed Alternating task, which were associated with smaller left
hippocampal volumes. There was no difference between groups in logical memory,
verbal learning or semantic clustering nor a significant correlation between
these measures and hippocampal volumes. Clinically, in SPD subjects, right
hippocampal volumes correlated negatively with odd appearance/behavior and
positively with suspiciousness/paranoia, and odd speech was positively correlated
with the number of slices containing a CSP in exploratory analyses. CONCLUSIONS:
Female SPD subjects showed bilaterally smaller hippocampal volumes and larger CSP
than comparison subjects, similar to what has been shown in schizophrenia.
Moreover, these abnormalities have clinically significant associations which may
help to explain some of the manifestations of the disorder.
PMID- 17027237
TI - CTX-M-1- and CTX-M-15-type beta-lactamases in clinical Escherichia coli isolates
recovered from food-producing animals in France.
AB - Clinical Escherichia coli strains with resistance or variable susceptibility to
third-generation cephalosporins were detected in cattle, swine and poultry in
France. These strains were shown to produce extended-spectrum beta-lactamases
(ESBLs), with CTX-M-1- and CTX-M-15-type beta-lactamases being responsible for
this phenotype. The bla(CTX-M-1) gene was encountered most commonly and was
characterised in seven E. coli strains isolated from cattle, swine and poultry,
whereas bla(CTX-M-15) was identified in one E. coli isolated from cattle. These
genes were located on a conjugative plasmid and were linked to the insertion
sequence ISEcp1, which could have contributed to dissemination of the resistance
gene. No epidemiological link between the strains was determined by pulsed-field
gel electrophoresis, although two plasmids were identical in two strains isolated
from swine and in two strains isolated from cattle and poultry. Thus, this study
describes the emergence of ESBLs in animals in France, with a probable similar
prevalence rate to that observed in humans. This is a major concern because of
the possibility of transfer of these genes between animal species as well as to
humans, leading to treatment failures in veterinary and human medicine.
PMID- 17027238
TI - Fate map of the distal portion of Drosophila proboscis as inferred from the
expression and mutations of basic patterning genes.
AB - The late-third-instar labial disc is comprised of two disc-proper cell layers,
one representing mainly the ventral half of the anterior compartment (L-layer)
and the other, the dorsal half of the anterior compartment and most, if not all,
of the posterior compartment (M-layer). In the L-layer, Distal-less represses
homothorax whereas no Distal-less-dependent homothorax repression occurs in the M
layer where Distal-less is coexpressed with homothorax. In wild-type labial
discs, clawless, one of the two homeobox genes expressed in distal cells
receiving maximum (Decapentaplegic+Wingless) signaling activity in leg and
antennal discs, is specifically repressed by proboscipedia. A fate map, inferred
from data on basic patterning gene expression in larval and pupal stages and
mutant phenotypes, indicates the inner surface of the labial palpus, which
includes the pseudotracheal region, to be a derivative of the distal portion of
the M-layer expressing wingless, patched, Distal-less and homothorax. The outer
surface of the labial palpus with more than 30 taste bristles derives from an L
layer area consisting of dorsal portions of the anterior and posterior
compartments, each expressing Distal-less. Our analysis also indicates that, in
adults and pupae, the anterior-posterior boundary, dividing roughly equally the
outer surface of the distiproboscis, runs along the outer circumference of the
inner surface of distiproboscis.
PMID- 17027239
TI - Dlx5- and Dlx6-mediated chondrogenesis: Differential domain requirements for a
conserved function.
AB - During endochondral ossification in the vertebrate limb, multipotent mesenchymal
cells first differentiate into chondroblasts (chondrogenesis) that further
differentiate (via chondrocyte hypertrophy) to a terminal cellular phenotype.
Dlx5 and Dlx6 are functionally redundant regulators of chondrocyte hypertrophy.
We now show that Dlx5 and Dlx6 also regulate the earlier step of chondrogenesis
in the limb. Limb bud mesenchymal cells from Dlx5/6(-/-) embryos show reduced
chondrogenesis compared to wild-type littermates, and expression of either Dlx5
or Dlx6 stimulated differentiation of limb bud mesenchymal cells to
chondroblasts. The functional overlap between Dlx5 and Dlx6 occurs despite the
fact that the amino- and carboxyl-terminal domains of the encoded proteins are
dissimilar. In order to reconcile the disparity between the divergent structures
of Dlx5 and Dlx6 with their overlapping biological functions, we investigated the
domain requirements and transcriptional activities associated with Dlx5- and Dlx6
mediated chondrogenesis. We find distinct domain requirements for the
chondrogenic function of these related homeoproteins, indicating divergent
molecular mechanisms of action.
PMID- 17027240
TI - [Maffucci syndrome: an historical case].
AB - We report a case of Maffucci syndrome in a 24-year-old patient, diagnosed thanks
to the data of the clinical examination, the imagery and the histology. The
clinical, radiological and evolutionary aspects are discussed, as well as the
various therapeutic means.
PMID- 17027241
TI - Extending temporal databases to deal with telic/atelic medical data.
AB - OBJECTIVE: In this paper, we aim at defining a general-purpose data model and
query language coping with both "telic" and "atelic" medical data. BACKGROUND: In
the area of Medical Informatics, there is an increasing realization that temporal
information plays a crucial role, so that suitable database models and query
languages are needed to store and support it. However, despite the wide range of
approaches in the area, in this paper we show that a relevant class of medical
data cannot be properly dealt with. METHODOLOGY: We first show that data models
based on the "point-based" semantics, which is (implicitly or explicitly) assumed
by the totality of temporal database approaches, have several limitations when
dealing with "telic" data. We then propose a new model (based on the "interval
based" semantics) to cope with such data, and extend the query language
accordingly. RESULTS: We propose a new three-sorted model and a query language to
properly deal with both "telic" and "atelic" medical data (as well as non
temporal data). Our query language is flexible, since it allows one to switch
from "atelic" to "telic" data, and vice versa. CONCLUSION: In this paper, we
demonstrate the feasibility of a database approach copying with both telic and
atelic data as needed in several (medical) applications.
PMID- 17027242
TI - Circulating homocysteine levels in patients with type 2 diabetes mellitus.
AB - BACKGROUND AND AIM: Previous studies have shown conflicting results regarding
circulating homocysteine levels in patients with type 2 diabetes. METHODS AND
RESULTS: This observational study included 2121 patients with angiographically
proven coronary artery disease (507 patients with type 2 diabetes and 1614
patients without diabetes). Circulating homocysteine levels,
methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, renal
function, presence of coronary artery disease (CAD) diagnosed by coronary
angiography, and circulating folate and vitamin B12 status were assessed. Plasma
homocysteine levels [median (25th; 75th percentile)] were significantly higher in
patients with diabetes than in those without [12.4 micromol/L (9.9 micromol/L;
15.9 micromol/L) versus 11.7 micromol/L (9.6 micromol/L; 14.5 micromol/L),
P=0.011]. Diabetes affected homocysteine levels only in patients with a
glomerular filtration rate <90 mL/min [13.0 micromol/L (10.5 micromol/L; 16.7
micromol/L) in patients with diabetes versus 12.2 micromol/L (10.1 micromol/L;
15.2 micromol/L) in patients without diabetes, P=0.006] but not in those with a
glomerular filtration rate > or = 90 mL/min [10.1 micromol/L (8.1 micromol/L;
12.4 micromol/L) versus 10.2 micromol/L (8.8 micromol/L; 12.3 micromol/L),
P=0.267]. Multivariable analysis did not show an independent association between
diabetes and homocysteine level (P=0.342). CONCLUSION: Circulating homocysteine
levels are increased in patients with type 2 diabetes compared with non-diabetic
patients due to a more diabetes-associated adverse risk profile rather than to
diabetes itself.
PMID- 17027243
TI - Fate of micelles and quantum dots in cells.
AB - Micelles and quantum dots have been used as experimental drug delivery systems
and imaging tools both in vitro and in vivo. Investigations of their fate at the
subcellular level require different surface-core modifications. Among the most
common modifications are those with fluorescent probes, dense-core metals or
radionucleids. Cellular fate of several fluorescent probes incorporated into
poly(caprolactone)-b-copolymer micelles (PCL-b-PEO) was followed by confocal
microscopy, and colloidal gold incorporated in poly 4-vinyl pyridine-PEO micelles
were developed to explore micelle fate by electron microscopy. More recently, we
have examined quantum dots (QDs) as the next-generation-labels for cells and
nanoparticulate drug carriers amenable both to confocal and electron microscopic
analyses. Effects of QDs at the cellular and subcellular levels and their
integrity were studied. Results from different studies suggest that size, charge
and surface manipulations of QDs may play a role in their subcellular
distribution. Examples of pharmacological agents incorporated into block
copolymer micelles, administered or attached to QD surfaces show how the final
biological outcome (e.g. cell death, proliferation or differentiation) depends on
physical properties of these nanoparticles.
PMID- 17027244
TI - Effect of surfactant on dissolution of spherical particles in micellar systems.
AB - The influence of micelle-drug solubilization on the dissolution rate of
monodisperse particles of benzocaine has been investigated. A model describing
and predicting the initial dissolution rates of spherical particles was derived
starting from the boundary layer theory. The dissolution rate of benzocaine
spherical particles was determined in water and in solutions of sodium lauryl
sulfate (SLS) under static conditions. The derived model was applied to the
experimental data. The diffusion coefficients and the aqueous diffusion layer
values were estimated from the experimental results and the aforementioned model.
The diffusion coefficients and the boundary layer thickness values were also
obtained experimentally from the rotating disk method and were used to predict
the initial dissolution rates. Excellent correlations were obtained between the
experimental and the calculated values at low micellar concentrations. However,
obvious deviation was observed at high micellar concentrations. The results
obtained from this study suggest that it is possible to predict the initial
dissolution rates of monodisperse particles in micellar systems.
PMID- 17027245
TI - Stable high surface area lactate dehydrogenase particles produced by spray
freezing into liquid nitrogen.
AB - Enzyme activities were determined for lactate dehydrogenase (LDH) powder produced
by lyophilization, and two fast freezing processes, spray freeze-drying (SFD) and
spray freezing into liquid (SFL) nitrogen. The 0.25 mg/mL LDH aqueous feed
solutions included either 30 or 100 mg/mL trehalose. The SFL process produced
powders with very high enzyme activities upon reconstitution, similar to
lyophilization. However, the specific surface area of 13 m(2)/g for SFL was an
order of magnitude larger than for lyophilization. In SFD activities were reduced
in the spraying step by the long exposure to the gas-liquid interface for 0.1-1s,
versus only 2 ms in SFL. The ability to produce stable high surface area
submicron particles of fragile proteins such as LDH by SFL is of practical
interest in protein storage and in various applications in controlled release
including encapsulation into bioerodible polymers. The SFL process has been
scaled down for solution volumes <1 mL to facilitate studies of therapeutic
proteins.
PMID- 17027246
TI - Predictors of asthma control in children from different ethnic origins living in
Amsterdam.
AB - To identify factors associated with asthma control in a multi-ethnic paediatric
population. We interviewed 278 children with paediatrician diagnosed asthma (aged
7-17 years) and one of their parents. Asthma control was assessed with the Asthma
Control Questionnaire (ACQ). Detailed information about sociodemographic
variables, asthma medication, knowledge of asthma, inhalation technique and
environmental factors were collected. Turkish and Moroccan parents were
interviewed in their language of choice. Logistic regression analyses were used
to identify correlates of asthma control. Of the 278 children, 85 (30.6%) were
Dutch, 84 (30.2%) were Moroccan, 58 (20.9%) were Turkish and 51 (18.3%) were
Surinamese. Overall, almost 60% had a status of well-controlled asthma, as
indicated by the ACQ. Only 51 of the 142 (35.9%) Moroccan and Turkish parents had
a good comprehension of the Dutch language. In logistic regression analyses the
risk of having uncontrolled asthma was significantly higher among Surinamese
children (OR 2.3; 95% CI 1.06-4.83), respondents with insufficient comprehension
of the Dutch language (OR 2.3; 95% CI 1.08-4.78), children using woollen blankets
(OR 9.8; 95% CI 1.52-63.42), and significantly lower among male (OR 0.5; 95% CI
0.31-0.91) and non-daily users of inhaled corticosteroids (OR 0.6; 95% CI 0.38
1.07). In conclusion, ethnicity as well as insufficient comprehension of the
Dutch language appeared to be independent risk factors for uncontrolled asthma.
Special attention should be given to children from immigrants groups for example
by calling in an interpreter by physicians when comprehension is insufficient.
PMID- 17027247
TI - Incidence and risk factors for ventilator-associated pneumonia in a developing
country: where is the difference?
AB - BACKGROUND: Latin America exhibits a wide range of differences, compared to
developed nations, in genetic background, health services, and clinical research
development. It is valid to hypothesize that the incidence and risk factors for
ventilator-associated pneumonia (VAP) in our setting may be substantially
different of those reported elsewhere. We conducted a study to determine the
incidence and risk factors for VAP in a University Hospital from Medellin,
Colombia. METHODS: Prospective cohort study in three intensive care units (ICU)
(surgical/trauma, medical, cardiovascular) in a 550-bed University Hospital.
Critically ill patients (n=270) who required at least 48 h of mechanical
ventilation (MV) between June 2002 and October 2003 were followed until ICU
discharge, VAP diagnosis or death. RESULTS: Sixty patients (22.2%) developed VAP
5.9+/-3.6 days after admission. The overall incidence of VAP was 29 cases per
1000 ventilator-days. The daily hazard for developing VAP increased until day 8,
and then decreased over the duration of stay in the ICU. The only statistically
significant factor after multivariable analysis was gender, with being female
reducing 57% the risk of pneumonia (hazard ratios (HR): 0.43; 95% confidence
intervals (CI): 0.19-0.96). CONCLUSIONS: The epidemiologic profile of VAP in
terms of incidence, length of stay and clinical course resembles the general
pattern described everywhere. Surprisingly, we could not identify any potentially
modifiable risk factor for VAP. A comprehensive multicenter study is warranted.
It should provide deep insight about the specific microbiological, genetic and
clinic features of VAP in our setting.
PMID- 17027248
TI - Quantifying the availability and the stability of trace cationic elements in fly
ash.
AB - For adsorption-desorption controlled leaching processes, the total leachable mass
and the adsorption constant are parameters representing the availability and the
stability of trace elements in solid media. With these parameters, one can
predict the leaching behavior of trace elements from solids under various pH and
solid-to-liquid ratio conditions. An approach was developed in this paper to
determine these parameters for model elements Cu(II), Cd(II), and Ni(II) in fly
ash. This approach consists of a batch equilibrium titration, a batch equilibrium
leaching with and without target element addition, and mathematical modeling.
Results indicated that the adsorption constant of a trace element can be
determined by modeling the adsorption ratio of the added element to the system as
a function of pH. Results also indicated that the trace element originally
present in fly ash had similar adsorption-desorption behavior as that added
externally. By modeling the batch leaching data with and without external element
addition, the total leachable mass and adsorption constant of the target element
can be determined simultaneously. The total leachable mass is in agreement with
experimental data from 50mM EDTA extraction.
PMID- 17027249
TI - Flexible manipulation of microfluids using optically regulated
adsorption/desorption of hydrophobic materials.
AB - To realize highly integrated micro total analysis systems (microTAS), a simply
controlled miniaturized valve should be utilized on microfluidic device. In this
paper, we describe the application of photo-induced super-hydrophilicity of
titanium dioxide (TiO2) to microfluidic manipulation. In addition, we found a new
phenomenon for reversibly converting the surface wettability using a
polydimethylsiloxane (PDMS) matrix and the photocatalytic properties of TiO2.
While PDMS polymer was irradiated with UV, it was confirmed that hydrophobic
material was released from the polymer to air. Several prepolymers were
identified as the hydrophobic material with a gas chromatograph and mass
spectrometer (GC/MS). Here, we successfully demonstrated the flexible
manipulation of microfluid in a branched microchannel using the reversible
wettability as micro opto-switching valve (MOS/V). The simultaneous control of
MOS/Vs was also demonstrated on a 256-MOS/V integrated disk. The MOS/V promises
to be one of the most effective flow switching valves for advanced applications
in highly integrated micro/nano fluidics.
PMID- 17027250
TI - A biomolecule friendly photolithographic process for fabrication of protein
microarrays on polymeric films coated on silicon chips.
AB - The last years, there is a steadily growing demand for methods and materials
appropriate to create patterns of biomolecules for bioanalytical applications.
Here, a photolithographic method for patterning biomolecules onto a silicon
surface coated with a polymeric layer of high protein binding capacity is
presented. The patterning process does not affect the polymeric film and the
activity of the immobilized onto the surface biomolecules. Therefore, it permits
sequential immobilization of different biomolecules on spatially distinct areas
on the same solid support. The polymeric layer is based on a commercially
available photoresist (AZ5214) that is cured at high temperature in order to
provide a stable substrate for creation of protein microarrays by the developed
photolithographic process. The photolithographic material consists of a
(meth)acrylate copolymer and a sulfonium salt as a photoacid generator, and it is
lithographically processed by thermal treatment at temperatures 93%, while the specific growth rate and enzyme activity were increased by
200% and 29%, respectively. The rate of conversion of the substrate was also very
high in the cells grown in optimized medium. The volumetric productivity of the
biotransformation process was much higher (0.27g/lh) with the cells grown in the
optimized medium compared to that of grown in un-optimized medium (0.16g/lh). The
cells were also highly stable in the operational condition, indicating the
feasibility of their use in multiple batches of reaction.
PMID- 17027260
TI - Design and effective synthesis of novel templates, 3,7-diphenyl-4-amino-thieno
and furo-[3,2-c]pyridines as protein kinase inhibitors and in vitro evaluation
targeting angiogenetic kinases.
AB - A novel class of 3,7-diphenyl-4-amino-thieno and furo[3,2-c]pyridine has been
designed based on pharmacophore models of ATP competitive kinase inhibitors.
Versatile synthetic methods via double Suzuki coupling to explore SAR have been
established and potent inhibitors against angiogenetic targets, VEGFR2, Tie-2,
and EphB4, have been successfully discovered.
PMID- 17027261
TI - Discovery of low nanomolar non-hydroxamate inhibitors of tumor necrosis factor
alpha converting enzyme (TACE).
AB - Using a pyrimidine-2,4,6-trione motif as a zinc-binding group, a series of
selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) was
discovered. Optimization of initial lead 1 resulted in a potent inhibitor (51),
with an IC(50) of 2 nM in a porcine TACE assay. To the best of our knowledge,
compound 51 and related analogues represent first examples of non-hydroxamate
based inhibitors of TACE with single digit nanomolar potency.
PMID- 17027262
TI - Discovery and initial development of a novel class of antibacterials: inhibitors
of Staphylococcus aureus transcription/translation.
AB - The novel bacterial transcription/translation (TT) inhibitor 1 was identified
through a combination of high throughput screening and exploratory medicinal
chemistry. Initial optimization of the anthranilic acid moiety and sulfonamide
amine diversity was accomplished via 1- and two-dimensional solution phase
libraries, resulting in an improvement in the MIC of the lead from 64 to 8mug/mL
(compound 4l). Subsequent modification of the central aromatic ring and further
refinement of the sulfonamide amines required the development of a solid phase
route on Wang resin. The resulting libraries generated a number of potent
antibacterials with MICs of 1mug/mL (e.g., 10b, 12, and 13). During the course of
this work, it became apparent that the antibacterial activity of the series is
not fully correlated with TT inhibition, suggesting that at least one additional
mechanism of action is operative.
PMID- 17027263
TI - Identification of novel, orally bioavailable spirohydantoin CGRP receptor
antagonists.
AB - A rapid analogue approach to identification of spirohydantoin-based CGRP
antagonists provided novel, low molecular weight leads. Modification of these
leads afforded a series of nanomolar benzimidazolinone-based CGRP receptor
antagonists. The oral bioavailability of these antagonists was inversely
correlated with polar surface area, suggesting that membrane permeability was a
key limitation to absorption. Optimization provided compound 12, a potent CGRP
receptor antagonist (K(i)=21nM) with good oral bioavailability in three species.
PMID- 17027264
TI - New pyrimido[5,4-b]indoles and [1]benzothieno[3,2-d]pyrimidines: high affinity
ligands for the alpha(1)-adrenoceptor subtypes.
AB - A number of new pyrimido[5,4-b]indole and [1]benzothieno[3,2-d]pyrimidine
derivatives were synthesized and evaluated for their binding and functional
properties at alpha(1)-adrenergic receptor (alpha(1)-AR) subtypes. They behaved
as potent alpha(1)-AR antagonists. In binding experiments, some of them (RC24 and
RC23) showed very high affinity for the alpha(1D)-AR subtype.
PMID- 17027265
TI - Synthesis of antimicrobial 2,9,10-trisubstituted-6-oxo-7,12-dihydro-chromeno[3,4
b]quinoxalines.
AB - A new series of 2,9,10-trisubstituted-6-oxo-7,12-dihydro-chromeno[3,4
b]quinoxalines was synthesized and submitted to antibacterial and antifungal
activities. Result of the antimicrobial screening showed the compound 4j being
the most effective among the various treatments in antimicrobial screening.
Compounds 4c, 4d, 4k, and 4l showed moderate activity against the microorganisms
tested.
PMID- 17027266
TI - Binding affinity prediction of non-peptide inhibitors of HIV-1 protease using
COMBINE model introduced from peptide inhibitors.
AB - Comparative binding energy (COMBINE) analysis method is one of the QSAR
techniques for the prediction of biological activities of inhibitors based on
interaction energies between ligands and proteins decomposed into each amino acid
residue. We supposed that the predictive ability of the COMBINE method does not
depend essentially on the molecular frameworks of ligands. To verify this idea,
we performed the COMBINE analysis of non-peptide inhibitors of HIV-1 protease
(HIVp), where the prediction model was constructed using inhibitors with a
peptide scaffold as a training set. The predictive performance of the AMBER and
CHARMm force fields was very high and at the same level (q(2)=0.75, 0.67,
SDEP(cv)=0.76, 0.89, and SDEP(ex)=0.92, 0.66, respectively). The high predictive
ability of the COMBINE method for the distinct scaffold compounds is due to the
informative description of the interaction energies for compounds that are
located at the binding site. This result suggests that COMBINE analysis may be
applied not only to the lead optimization stage but also to the lead evolution
stages.
PMID- 17027267
TI - Design, synthesis, and biological evaluation of new (2E,6E)-10-(dimethylamino)
3,7-dimethyl-2,6-decadien-1-ol ethers as inhibitors of human and Trypanosoma
cruzi oxidosqualene cyclase.
AB - New dimethylamino truncated squalene ether derivatives containing a different
aromatic moiety (phenyl, naphthyl, and biphenyl) or a simple alkyl (n-hexylic)
group were synthesized as inhibitors of the oxidosqualene cyclase (OSC) and of
the sterol biosynthetic pathway. The activity against human OSC was compared with
the activity against the OSCs of pathogenic organisms such as Pneumocystis
carinii and Trypanosoma cruzi. The phenyl derivative was the most potent
inhibitor of T. cruzi OSC.
PMID- 17027268
TI - New antifungal flavonoid glycoside from Vitex negundo.
AB - Flavonoids are ubiquitous in photosynthesizing cells and are common part of human
diet. For centuries, preparations containing these compounds as the principal
physiologically active constituents have been used to treat human diseases.
Increasingly, this class of natural products is becoming the subject of anti
infective research. Our bioactivity guided fractionation of ethanolic extract of
leaves of Vitex negundo resulted in the isolation of new flavone glycoside (4)
along with five known compounds 1-3, 5 and 6. All the isolated compounds were
evaluated for their antimicrobial activities. The new flavone glycoside 4 and
compound 5 were found to have significant antifungal activity against
Trichophyton mentagrophytes and Cryptococcus neoformans at MIC 6.25 microg/ml.
PMID- 17027269
TI - Arylsulfonamides as a new class of cannabinoid CB1 receptor ligands:
identification of a lead and initial SAR studies.
AB - High-throughput screening of the UCB sample collection identified the piperidinyl
sulfonyl benzoic ester 1 as a novel agonist for CB(1) receptor with nanomolar
affinity. We report here the pharmacological profile of compound 1 as well as
preliminary biological activities in pain model. Diverse close analogs of 1 were
purchased and the structure-affinity relationships among this novel class are
discussed.
PMID- 17027270
TI - Improved 3D-QSAR CoMFA of the dopamine transporter blockers with multiple
conformations using the genetic algorithm.
AB - A 3D-QSAR/CoMFA was performed for a series of 42 piperidine-based dopamine
transporter (DAT) blockers. The overall process consisted of three major steps:
(1) a pharmacophore model was built using the Genetic Algorithm Similarity
Program (GASP); (2) the Flexible Superposition (FlexS) technique was applied to
generate multiple conformations for each of the ligands based on the
pharmacophore; (3) the Genetic Algorithm was employed to optimize the selection
of the ligand conformations for the CoMFA modeling. The CoMFA models were found
to be more detailed in the putative binding site by exploring multiple
conformations of each ligand. The comparison of the contour maps shows that, in
general, these models are comparable and the differences between them result from
the ability of the flexible 3alpha-substituents of the ligands to adopt multiple
conformations satisfying the same pharmacophore model. These findings provide
guidance for the design and improvement of compounds with DAT activity, which is
important for the development of a treatment of cocaine addiction and certain
neurological disorders.
PMID- 17027271
TI - Natural inhibitors targeting osteoclast-mediated bone resorption.
AB - Human cathepsin K, matrix metalloproteinase 9, and alpha(V)beta(3) integrin are
the key regulators in osteoclast-mediated bone resorption. In this paper, we
found natural inhibitors 1-10 for them by enzyme inhibition assays. Inhibitors 1
7, 8-9, and 10 are novel inhibitors of human cathepsin K, matrix
metalloproteinase 9, and alpha(V)beta(3), respectively.
PMID- 17027272
TI - SAR studies of 6-(arylamino)-4,4-disubstituted-1-methyl-1,4-dihydro
benzo[d][1,3]oxazin-2-ones as progesterone receptor antagonists.
AB - We previously disclosed that 6-aryl benzoxazin-2-ones were PR modulators. In a
continuation of this work we examined the SAR of new 6-arylamino benzoxazinones
and found the targets 1-25, with an extra amino linker between the pendent 6-aryl
groups and benzoxazinone or benzoxazine-2-thione core, were PR antagonists. A
series of compounds with substituents at the 1- and 4-positions as well as
different 6-aryl groups were prepared and tested in the T47D cell alkaline
phosphatase assay. Interestingly, the SAR unveiled from the 6-arylamino
benzoxazinones was quite different from those of their parent compounds. For
example, in contrast to the 6-aryl benzoxazinones, methyl substitution at the 1
position significantly increased the potency of 6-arylamino benzoxazinones.
Several 6-arylamino benzoxazinones (e.g., 12, IC(50)=5.0 nM) had low nanomolar in
vitro potency as PR antagonists in the T47D cell alkaline phosphatase assay.
PMID- 17027273
TI - CLOCK leaves its mark on histones.
AB - Transcriptional regulation of circadian rhythms in mammals involves a negative
feedback loop whereby a CLOCK-BMAL1 complex activates transcription of the genes
encoding the proteins PER1 (Period 1), PER2, CRY1 (Cryptochrome 1) and CRY2,
which feed back to inhibit the activity of CLOCK-BMAL1. It is becoming evident
that chromatin remodeling has a crucial role in the transcriptional regulation of
genes governing circadian rhythms. This is highlighted in a recent report that
shows that CLOCK has histone acetyltransferase activity, thus, demonstrating that
molecular components of the biological clock can themselves catalyze chromatin
modifications.
PMID- 17027274
TI - Determinants of drug brain uptake in a rat model of seizure-associated
malformations of cortical development.
AB - We examined the blood-brain barrier (BBB) function in methylazoxymethanol acetate
(MAM)-treated rats, a model of human developmental brain malformations. We found
aberrant vessels morphology and serum albumin leakage in the heterotopic
(malformed) hippocampus; these changes were associated with a significant
increase in endothelial P-glycoprotein (P-gp) expression. Seizures exacerbated
BBB leakage and greatly augmented P-gp expression in vessels and additionally in
perivascular/parenchymal astrocytes. The effects of seizures were observed to a
much larger extent in malformed than in normal brain tissue. The intrinsic
changes in BBB function in MAM-exposed rats were associated with increased blood
to-brain penetration of ondansetron, a P-gp substrate. However, a marked
reduction in drug brain levels was provoked by seizures, and this effect was
reversed by selective blockade of P-gp activity with tariquidar. Changes in BBB
function may critically contribute to determine the brain uptake and distribution
of P-gp substrates in epileptic tissue associated with developmental
malformations.
PMID- 17027275
TI - Interleukin-1beta mediates GDNF up-regulation upon dopaminergic injury in ventral
midbrain cell cultures.
AB - We recently proposed the involvement of diffusible modulators in signalling
astrocytes to increase glial cell line-derived neurotrophic factor (GDNF)
expression after selective dopaminergic injury by H2O2 or L-DOPA. Here we report
that interleukin-1beta (IL-1beta) is involved in this crosstalk between injured
neurons and astrocytes. IL-1beta was detected only in the media from challenged
neuron-glia cultures. Exogenous IL-1beta did not change GDNF protein levels in
astrocyte cultures, and diminished GDNF levels in neuron-glia cultures. This
decrease was not due to cell loss, as assessed by the MTT assay and
immunocytochemistry. Neither H2O2 nor L-DOPA induced microglia proliferation or
appeared to change its activation state. The IL-1 receptor antagonist (IL-1ra)
prevented GDNF up-regulation in challenged cultures, showing that IL-1beta is
involved in the signalling between injured neurons and astrocytes. Since IL-1ra
decreased the number of dopaminergic neurons in H2O2-treated cultures, we propose
that IL-1 has a neuroprotective role in this system involving GDNF up-regulation.
PMID- 17027276
TI - Characterization of plant phenotypes associated with loss-of-function of AtCNGC1,
a plant cyclic nucleotide gated cation channel.
AB - Of the 57 cation channel genes in the Arabidopsis genome, over a third encode
cyclic nucleotide gated cation channels (CNGCs). CNGCs are ion channels regulated
by cytosolic signaling molecules (cyclic nucleotides, calmodulin, and Ca(2+)),
and which conduct Ca(2+) as well as K(+) and in some cases Na(+). Little is
currently known about the role CNGCs may play in plant growth and development.
Here, we examined the hypothesis that an Arabidopsis thaliana genotype containing
a null mutation in one of the CGNC genes (AtCNGC1) would display cation uptake
related growth phenotype differences from wild type (WT) plants. We determined
that AtCNGC1 protein is primarily expressed in the roots of Arabidopsis
seedlings. Seedlings lacking this protein had slightly (6-22%) lower shoot Ca(2+)
than WT plants. Primary roots of Atcngc1 mutant seedlings grew faster than roots
of WT plants, and had larger angles of gravicurvature and less nitric oxide
generation upon gravistimulation. We conclude that channels formed (at least in
part) by AtCNGC1 contribute (along with other channels) to Ca(2+) uptake into
plants, and that Ca(2+) uptake into roots through AtCNGC1 affects some aspects of
growth in the primary root of Arabidopsis seedlings.
PMID- 17027277
TI - Risk factors for mortality and hospital re-admission after surgical ventricular
restoration.
AB - BACKGROUND: Surgical ventricular restoration is an option in patients with
coronary artery disease, heart failure, postinfarction left ventricular aneurysm
or ischemic dilated cardiomyopathy with or without ventricular tachycardia. The
aims of this study were to investigate survival and re-admission for heart
failure and to identify predictors for early and long-term mortality and re
admission after surgical ventricular restoration. METHODS: Pre- and postoperative
data were collected for 136 consecutive patients who underwent surgical
ventricular restoration for postinfarction left ventricular aneurysm or ischemic
dilated cardiomyopathy during 1994-2005. Survival and risk factors for mortality
and hospital re-admission were analyzed by using multivariable models. RESULTS:
Early mortality was 10/136 (7.4%). At 1, 3, 5 and 9 years overall actuarial
survival was 89%, 80%, 68% and 62%. Increasing age, diabetes and mitral
regurgitation grade III-IV were associated with an increased risk for late
mortality. Freedom from re-hospitalization due to heart failure or cardiac death
in operative survivors at 1, 3 and 5 years was 78%, 72% and 58%. Risk factors for
re-hospitalization or cardiac death in operative survivors were increasing age
and increasing grade of mitral regurgitation. CONCLUSIONS: Surgical ventricular
restoration by the Dor procedure can achieve good long-term survival and a high
degree of freedom from readmission for heart failure in patients with advanced
ischemic heart disease. We found a strong association between increasing grade of
mitral regurgitation and both long-term mortality and re-admission for heart
failure.
PMID- 17027278
TI - Glioblastoma in the elderly: current and future trends.
AB - Data from a prospective trial large enough to provide a reliable analysis of
outcome and prognostic factors in elderly patients with glioblastoma (GBM) are
not yet available in the literature. Extensive tumor removal appears to offer
patients the best possible chance of a speedy neurological recovery. Adequate
radiotherapy (RT) should always be given to elderly patients if they have
undergone gross total debulking and have maintained a good performance status. It
is, however important to bear in mind that the risk of long-term cognitive
impairment may be higher in patients on high-dose RT and that a short course of
accelerated RT can achieve the same survival. Rather than being ruled out on
principle, chemotherapy should be considered on the basis of an accurate
assessment of the factors that might compromise the individual patient's
tolerance to drugs administered. Temozolomide appears to be the best available
chemotherapy in this population of patients.
PMID- 17027279
TI - Should concomitant and adjuvant treatment with temozolomide be used as standard
therapy in patients with anaplastic glioma?
AB - Malignant gliomas are devastating tumors associated with poor prognosis. Standard
treatment has been surgery followed by radiotherapy while the role of
chemotherapy has remained controversial. Concomitant and adjuvant treatment with
temozolomide has recently been shown to improve survival in patients with
glioblastoma. While it seems intuitive to apply this regimen to patients with
anaplastic gliomas which have traditionally been considered more chemosensitive,
chemotherapy has not been shown to prolong life in patients with anaplastic
gliomas. Despite promising preclinical and early clinical results, there is
currently not enough level 1 evidence to justify concomitant and adjuvant
temozolomide as standard therapy for patients with newly diagnosed anaplastic
gliomas. Further investigation is needed to better define the role of
chemotherapy in patients with anaplastic gliomas. Trials evaluating
chemoradiotherapy as well as targeted therapeutic agents are the subject of
further research.
PMID- 17027280
TI - Proinflammatory cytokines (TNF-alpha and IL-6) in Egyptian patients with SLE: its
correlation with disease activity.
AB - BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disease
characterized by a wide variety of autoantibodies, some of which are pathogenic.
In recent years it has become more evident that the polyclonal B cell activation
in SLE is T-cell dependent. The stimulation of the autoantibody producing B cells
is likely mediated by the TH2 subtype of T cells producing IL-4, IL-5, IL-6 and
IL- 10, whereas the TH1 subtype secreting IL-2 and IFN-gamma predominates in cell
mediated immune response. Tumor Necrosis Factor (TNF-alpha) is both a
proinflammatory and an immunoregulatory cytokine. TNF-alpha has differential
effects on B cells, on T cells and on dendritic cells as well as on the process
of programmed cell death. Understanding how the immune system integrates the
pleiotropic properties of TNF-alpha is a challenge, particularly so in diseases
like SLE. Meanwhile the role of IL-6 in the pathogenesis of SLE is controversial.
OBJECTIVE: To investigate whether serum levels of TNF-alpha and IL-6 is higher in
Egyptian patients with SLE than healthy control volunteers and its correlation
with the clinical activity in patients with different activity scores as measured
by Systemic Lupus Erythmatosus Disease Activity Index (SLEADI). METHODS: Sixty
individuals (40 patients with Systemic lupus Erythmatosus and 20 healthy control
volunteers) were the subject of this study, they were subjected to thorough
clinical examination, laboratory investigations, their clinical disease activity
was scored according to SLEDAI, and serum sampling was obtained for TNF-alpha and
IL-6 levels assay. Renal biopsy was carried out and examined by light microscopy
by a pathologist blinded with the clinical activity. RESULTS: The mean level of
TNF-alpha was (766.95+/-357.82Pg/ml) for patients with active disease while it
was (314.01+/-100.87Pg/ml) for those with inactive disease and (172.7+/
39.19Pg/ml) for the healthy control group. The difference was statistically
significant (P=.002). The mean level of IL-6 was (135.4+/-54.23Pg/ml) for
patients with active disease while it was (47.33+/-18.61Pg/ml) for those with
inactive disease and (21.15+/-10.99Pg/ml) for the healthy control group. The
difference was statistically significant (P=.002). A significant correlations
between TNF-alpha and IL-6 serum levels and the SLEDAI score was observed (r=.743
and .772, respectively). CONCLUSION: Serum TNF-alpha and IL-6 are sensitive
markers of SLE disease activity. They may be useful independent markers for
prediction of SLE disease activity and to differentiate normal subjects from
those having SLE. Possible therapeutic implications in the treatment of SLE in
the future deserve wide scale trials.
PMID- 17027281
TI - The role of the CD95, CD38 and TGFbeta1 during active human cytomegalovirus
infection in liver transplantation.
AB - AIM: Human cytomegalovirus (HCMV) has highly evolved mechanisms for avoiding
detection by the host immune system. The aim of this study was to analyze the
expression levels of TGFbeta1, soluble form of CD95, CD95 ligand (sCD95 and
sCD95L, respectively) in plasma and CD95 expression on CD3(+) cells, CD38
expression on CD8(+) cells in liver transplanted recipients with active HCMV
infection. METHODS: Blood samples were collected from 15 liver transplanted
recipients with active HCMV infection and 15 recipients without HCMV infection.
CD95 expression on CD3(+) cells and CD38 expression on CD8(+) cells were
quantitatively detected with two-color fluorescence activated cell sorter (FACS)
analysis. Lymphocyte surface phenotypes of CD4 and CD8 were detected with FACS
analysis. Plasma sCD95, sCD95L and TGFbeta1 levels were determined with enzyme
linked-immuno-sorbent assay (ELISA). The results were compared with that from 15
healthy individuals. RESULTS: CD95 expression on CD3(+) T-cells and CD38
expression on CD8(+) cells were significantly increased in active HCMV infection
group compared with that in stable group or healthy group (P<0.01). No
significant difference was seen between stable group and healthy group (P>0.05).
The percentages of CD4(+) T-cell and CD4/CD8 ratio in active HCMV infection group
were significantly lower than the values in stable group and healthy group
(P<0.05). Plasma levels of TGFbeta1 and sCD95 were significantly increased in
active HCMV infection group compared to stable group and healthy group (P<0.05).
In contrast, plasma levels of sCD95L in healthy group were not significantly
different from that expressed in active HCMV infection group and stable group
(P>0.05). CONCLUSION: HCMV suppress proliferation of activated T cells by
apoptosis and by releasing immunosuppressive cytokine TGFbeta1. This may provide
an important clue to a better understanding of the pathogenesis in liver
transplanted recipients with active HCMV infection.
PMID- 17027282
TI - One-step affinity purification of recombinant urokinase-type plasminogen
activator receptor using a synthetic peptide developed by combinatorial
chemistry.
AB - Several lines of evidence have pointed to a role of urokinase-type plasminogen
activator receptor (uPAR) as a modulator of certain biochemical processes that
are active during tumor invasion and metastasis. Consequently, the structure and
function of this receptor have been studied extensively, using recombinantly
produced uPAR that has been purified by either affinity chromatography using its
cognate ligand, the urokinase-type plasminogen activator (uPA), or a monoclonal
anti-uPAR antibody (R2), or by hydroxyapatite. Here, we present a new method for
the efficient one-step affinity purification of recombinant uPAR exploiting a
high-affinity synthetic peptide antagonist (AE152). The corresponding parent
peptide was originally identified in a random phage-display library and
subsequently subjected to affinity maturation by combinatorial chemistry. This
study compares the affinity purification of a soluble, recombinant uPAR using the
monoclonal antibody R2 or the peptide AE152 immobilized on Sepharose. The two
affinity ligands perform equally well in purifying uPAR from Drosophila
melanogaster Schneider 2 cell culture medium and yield products of comparable
purity, activity, and stability as judged by SDS-PAGE, size exclusion
chromatography and surface plasmon resonance analysis. The general availability
of peptide synthesis renders the present AE152-based affinity purification of
uPAR more accessible than the traditional protein-based affinity purification
strategies. In this way, large amounts of recombinant uPAR can conveniently be
purified for further structural and functional studies.
PMID- 17027283
TI - Preparation and characterization of recombinant protein ScFv(CD11c)-TRP2 for
tumor therapy from inclusion bodies in Escherichia coli.
AB - Dendritic cells (DCs)-based immunotherapy represents an approach to the
prevention and treatment of cancers. Targeting antigens to receptors on DCs can
be expected to enhance immune response. We have constructed an expression vector
pET32a(+)-ScFv(CD11c)-TRP2 based on a single-chain antibody fragment (ScFv) that
targets the high affinity receptor CD11c which is expressed on murine DCs. The 3'
terminal end of the ScFv was ligated to the gene for MHC class I molecule
recognized peptide from mouse tyrosine-related protein 2 (TRP2). Using this
vector, we have expressed and purified ScFv(CD11c)-TRP2, a fusion protein that
could target TRP2 peptide to CD11c on DCs in vivo to elicit anti-tumor responses.
This fusion protein was expressed in inclusion bodies in Escherichia coli
BL21(DE3) and was refolded and purified on-column effectively by immobilized
metal affinity chromatography using His-tag. Flow cytometry assays showed the
specific binding ability of ScFv(CD11c)-TRP2 to DCs, which could be blocked by a
hamster anti-mouse CD11c produced by N418 hybridoma. Further studies demonstrated
that ScFv(CD11c)-targeted TRP2 peptide processed by DCs was capable of
stimulating T cells proliferation. Thus, this fusion protein provides a basis for
further research in cancer therapy in vivo.
PMID- 17027284
TI - Estimating osteoarthritis incidence from population-based administrative health
care databases.
AB - PURPOSE: The aim of the study is to develop a method to estimate osteoarthritis
(OA) incidence by using administrative health care databases. METHODS: Using
actual counts of OA diagnoses in different periods, we generated an equation that
estimated the number of new OA diagnoses based on the length of time used for
excluding prevalent OA cases. Physicians billing files from 1983 to 2002
maintained at Alberta Health and Wellness were used to verify the proposed
method. Age- and sex-specific and crude OA incidences in 2002 were calculated by
using this method. RESULTS: Women aged 50 to 59 years had the greatest incidence.
For men, the greatest incidence was in the 60- to 69-year age category. Crude
incidences for women and men were 1103 and 934 per 100,000 person-years,
respectively. The overall crude rate was 1040 per 100,000 person-years.
CONCLUSIONS: Modified power function accurately summarizes the relationship
between number of first OA diagnoses and length of the clearance period and thus
provides an effective model to estimate OA incidence. Not restricted to OA, this
model also can be implemented to estimate incidences of other chronic conditions.
PMID- 17027285
TI - Weight, height, and body mass index and risk for ovarian cancer in a cohort
study.
AB - PURPOSE: Reported associations between ovarian cancer and body size are
inconsistent. We assessed ovarian cancer and anthropometry in the Breast Cancer
Detection Demonstration Project Follow-Up Study. METHODS: The 46,026 participants
completed a baseline interview and mailed questionnaires between 1979 and 1998.
By using multiple sources, we identified 346 incident ovarian cancers during
follow-up. We calculated rate ratios (RRs) and 95% confidence intervals (CIs) to
estimate relative risks for developing ovarian cancer associated with height and
weight (measured 1973 to 1980) and self-reported current and usual adult weight
(collected during follow-up). RESULTS: Neither taller height (> or =66 versus <62
inches; RR, 0.90; 95% CI, 0.64-1.26) nor greater weight (> or =161 versus < or
=120 lbs; RR, 1.09; 95% CI, 0.77-1.55) was associated with ovarian cancer.
Compared with normal weight (body mass index [BMI], 18.5 to 24.9 kg/m(2)),
overweight (BMI, 25 to 29.9 kg/m(2); RR, 1.00; 95% CI, 0.78-1.29) and obesity
(BMI, 30 to 34.9 kg/m(2); RR, 0.94; 95% CI, 0.59-1.48) were not associated with
ovarian cancer. Severe obesity (BMI > or = 35 kg/m(2)) produced a
nonsignificantly elevated RR (1.55; 95% CI, 0.84-2.84). Associations with
histologic types and statistical interactions with menopausal status and hormone
therapy use were null. CONCLUSIONS: Based on height and weight measured before
baseline, overweight and obesity were not significantly associated with ovarian
cancer in this cohort.
PMID- 17027286
TI - Match rate and positional accuracy of two geocoding methods for epidemiologic
research.
AB - PURPOSE: This study compares the match rate and positional accuracy of two
geocoding methods: the popular geocoding tool in ArcGIS 9.1 and the Centrus
GeoCoder for ArcGIS. METHODS: We first geocoded 11,016 Texas addresses in a case
control study using both methods and obtained the match rate of each method. We
then randomly selected 200 addresses from those geocoded by using both methods
and obtained geographic coordinates of the 200 addresses by using a global
positioning system (GPS) device. Of the 200 addresses, 110 were case maternal
residence addresses and 90 were control maternal residence addresses. These GPS
surveyed coordinates were used as the "true" coordinates to calculate positional
errors of geocoded locations. We used Wilcoxon signed rank test to evaluate
whether differences in positional errors from the two methods were statistically
significantly different from zero. In addition, we calculated the sensitivity and
specificity of the two methods for classifying maternal addresses within 1500 m
of toxic release inventory facilities when distance is used as a proxy of
exposure. RESULTS: The match rate of the Centrus GeoCoder was more than 10%
greater than that of the geocoding tool in ArcGIS 9.1. Positional errors with the
Centrus GeoCoder were less than those of the geocoding tool in ArcGIS 9.1, and
this difference was statistically significant. Sensitivity and specificity of the
two methods are similar. CONCLUSIONS: Centrus GeoCoder for ArcGIS for geocoding
gives greater match rates than the geocoding tool in ArcGIS 9.1. Although the
Centrus GeoCoder has better positional accuracy, both methods give similar
results in classifying maternal addresses within 1500 m of toxic release
inventory facilities when distance is used as a proxy of exposure.
PMID- 17027287
TI - Confounder selection in environmental epidemiology: assessment of health effects
of prenatal mercury exposure.
AB - PURPOSE: The purpose of the study is to compare different approaches to the
identification of confounders needed for analyzing observational data. Whereas
standard analysis usually is conducted as if the confounders were known a priori,
selection uncertainty also must be taken into account. METHODS: Confounders were
selected by using backward elimination (BE), change in estimate (CIE) method,
Akaike information criterion, Bayesian information criterion (BIC), and an
empirical approach using a priori information. A modified ridge regression
estimator, which shrinks effects of confounders toward zero, also was considered.
For each criterion, uncertainty in the estimated exposure effect was assessed by
using bootstrap simulations for which confounders were selected in each sample.
These methods were illustrated by using data for mercury neurotoxicity in Faroe
Islands children. Point estimates and standard errors of mercury effects on
confounder-sensitive neurobehavioral outcomes were calculated for each selection
procedure. RESULTS: The full model and the empirical a priori model showed
approximately the same precision, and these methods were (slightly) inferior to
only modified ridge regression. Lower precisions were obtained by using BE with a
low cutoff level, BIC, and CIE. CONCLUSIONS: Standard analysis ignores model
selection uncertainty and is likely to yield overoptimistic inferences. Thus, the
traditional BE procedure with p = 5% should be avoided. If data-dependent
procedures are required for confounder identification, we recommend that
inferences be based on bootstrap statistics to describe the selection process.
PMID- 17027288
TI - Cognitive functioning in late life: the impact of moderate alcohol consumption.
AB - PURPOSE: Sex differences in the association between moderate alcohol consumption
and cognitive functioning were examined during 4 years. METHODS: Participants
were 2716 US older adults 70 years and older (mean age, = 76.02 years) who were
free of cognitive impairment from the Second Longitudinal Study of Aging (1994 to
2000). Multiple logistic regression models were used to predict cognitive
functioning (adapted Telephone Interview for Cognitive Status) from average daily
alcohol intake (no drink, one drink or less daily, and more than one drink daily)
during 4 years after controlling for covariates. RESULTS: Sex differences in the
association between alcohol consumption and cognitive functioning were found (p <
0.01). Older adults with alcohol consumption of one drink or less per day had a
lower odds of low cognitive functioning compared with abstainers for women
(adjusted odds ratio [AOR], 0.67; 95% confidence interval [CI], 0.55-0.83), but
not men (AOR, 0.96; 95% CI, 0.69-1.34). CONCLUSIONS: For older adults with a
level of cognitive functioning within normal ranges, moderate amounts of alcohol,
an average of one drink or less daily, was protective for women, but not men.
Caution should be used in suggesting moderate alcohol consumption to maintain
cognitive functioning because of the risks of consuming alcohol.
PMID- 17027289
TI - Modeling adolescent drug-use patterns in cluster-unit trials with multiple
sources of correlation using robust latent class regressions.
AB - PURPOSE: The purpose of the study is to examine variation in adolescent drug-use
patterns by using latent class regression analysis and evaluate the properties of
an estimating-equations approach under different cluster-unit trial designs.
METHODS: A set of second-order estimating equations for latent class models under
the cluster-unit trial design are proposed. This approach models the correlation
within subclusters (drug-use behaviors), but ignores the correlation within
clusters (communities). A robust covariance estimator is proposed that accounts
for within-cluster correlation. Performance of this approach is addressed through
a Monte Carlo simulation study, and practical implications are illustrated by
using data from the National Evaluation of the Enforcing Underage Drinking Laws
Randomized Community Trial. RESULTS: The example shows that the proposed method
provides useful information about the heterogeneous nature of drug use by
identifying two subtypes of adolescent problem drinkers. A Monte Carlo simulation
study supports the proposed estimation method by suggesting that the latent class
model parameters were unbiased for 30 or more clusters. Consistent with other
studies of generalized estimating equation (GEE) estimators, the robust
covariance estimator tended to underestimate the true variance of regression
parameters, but the degree of inflation in the test size was relatively small for
70 clusters and only slightly inflated for 30 clusters. CONCLUSIONS: The proposed
model for studying adolescent drug use provides an alternative to standard
diagnostic criteria, focusing on the nature of the drug-use profile, rather than
relying on univariate symptom counts. The second-order GEE-type estimation
procedure provided a computationally feasible approach that performed well for a
moderate number of clusters and was consistent with prior studies of GEE under
the generalized linear model framework.
PMID- 17027290
TI - Impact of hysterectomy and bilateral oophorectomy on race-specific rates of
corpus, cervical, and ovarian cancers in the United States.
AB - PURPOSE: Population-based cancer incidence rates of the corpus uteri, cervix
uteri, and ovaries are underestimated if they fail to remove women not at risk
for developing the cancers from the denominator in the race calculation. This
study compares incidence rates among selected racial groups for these cancers
before and after correction for prevalence of hysterectomy and bilateral
oophorectomy. METHODS: The study covers 1998 through 2002 and involves
Surveillance, Epidemiology, and End Results Program; Behavior Risk Factor
Surveillance System; and National Health Interview Survey data. Prevalence data
were obtained by using survey and life-table methods. Four racial groups are
considered: whites, blacks, American Indians/Alaska Natives, and Asians/Pacific
Islanders. RESULTS: Risk correction significantly increased rates of corpus
uterine cancer by 73.1% for whites, 93.0% for blacks, 86.3% for American
Indians/Alaska Natives, and 41.0% for Asians/Pacific Islanders. Corresponding
percentages among these racial groups for cervical cancer were 37.7%, 60.2%,
45.6%, and 33.0%, and for ovarian cancer, 32.5%, 31.1%, 35.0%, and 23.6%,
respectively. Risk correction had large influences on the comparison of rates
among racial groups. For example, for uterine corpus cancer, Asians/Pacific
Islanders had 32.9% lower rates than whites before correction, but 45.3% lower
rates after correction. For cervical cancer, blacks had 27.6% higher rates than
whites before correction, but 48.5% higher rates after correction; and for
ovarian cancer, Asians/Pacific Islanders had 31.2% lower rates than whites before
correction and 35.8% lower rates after correction. CONCLUSIONS: Corrected rates
of corpus uteri, cervix uteri, and ovarian cancers have a large, but
differential, impact on the racial groups considered.
PMID- 17027291
TI - Regarding "selection and recall bias in a case-control study of lifetime alcohol
intake and breast cancer risk".
PMID- 17027292
TI - Cumulative socioeconomic status across the life course and subclinical
atherosclerosis.
AB - PURPOSE: The purpose of this study is to investigate the relationship between
individual-level and neighborhood-level socioeconomic status (SES) across the
life course and subclinical atherosclerosis. METHODS: Participants from the
Atherosclerosis Risk in Communities Study (n=12,332) were queried about
individual-level SES and residential addresses across the life course. Individual
level measures were scored and summed to obtain a summary score (I-CumSES),
whereas residential addresses were geocoded and linked to census data to obtain a
summary neighborhood z score (N-CumSES) to evaluate the association of SES with
intima-media thickness (IMT) and peripheral arterial disease (PAD). RESULTS: A 1
SD lower I-CumSES was associated with greater mean IMT in each race-sex group and
greater odds of PAD in white men (odds ratio [OR], 1.28; 95% confidence interval
[CI], 0.99-1.64), white women (OR, 1.18; 95% CI, 1.02-1.36), and black women (OR,
1.33; 95% CI, 1.00-1.76). Compared with the highest tertile of N-CumSES, the
lowest tertile was associated with greater mean IMT among whites, but was not
associated with PAD for whites or blacks. When I-CumSES and N-CumSES were
considered simultaneously, associations remained for only I-CumSES and were
attenuated after adjustment for cardiovascular disease (CVD) risk factors.
CONCLUSIONS: Lower cumulative individual-level SES across the life course was
associated with a greater burden of subclinical atherosclerosis, and this
association was mediated in part by CVD risk factors.
PMID- 17027293
TI - Suicide risk among Chernobyl cleanup workers in Estonia still increased: an
updated cohort study.
AB - PURPOSE: The aim of the study is to examine the mortality experience among
Chernobyl cleanup workers. METHODS: A cohort study of 4786 men from Estonia who
participated in the Chernobyl cleanup from 1986 to 1991 and were traced until
December 31, 2002. Standardized mortality ratio (SMR) and adjusted mortality rate
ratio (RR) derived through Poisson regression analysis were calculated. RESULTS:
During follow-up, 550 deaths occurred, yielding an SMR of 1.01 (95% confidence
interval [CI], 0.92-1.09). Increased risks were observed for suicide alone (SMR,
1.32; 95% CI, 1.03-1.67) and suicide combined with undetermined injury (SMR,
1.29; 95% CI, 1.03-1.60). One leukemia death occurred, and no thyroid cancer
deaths were found. Elevated mortality also was observed for brain cancer (SMR,
2.78; 95% CI, 1.02-6.05). The adjusted RR for suicide remained stable over the
time passed since return from the Chernobyl area, showing RRs of 1.09 (95% CI,
0.56-2.10) for 5 to 9 years and 1.00 (95% CI, 0.48-2.05) for 10 or more years
compared with less than 5 years. CONCLUSIONS: During the 17 years after the
accident, suicide risk in the cohort was greater than in the general male
population. No elevated risk in overall mortality and radiation-related cancers
was observed. The long-term nature of this elevated risk provides concrete
evidence that psychological consequences represent the largest public health
problem caused by the accident to date.
PMID- 17027295
TI - Severe back pain among farmworker high school students from Starr County, Texas:
baseline results.
AB - PURPOSE: This cohort study is among the first to estimate the prevalence of and
examine potential risk factors for severe back pain (resulting in medical care,
4+ hours of time lost, or pain lasting 1+ weeks) among adolescent farmworkers.
These youth often perform tasks requiring bent/stooped postures and heavy
lifting. METHODS: Of 2536 students who participated (response rate across the
three public high schools, 61.2% to 83.9%), 410 students were farmworkers
(largely Hispanic and migrant). Students completed a self-administered Web-based
survey including farm work/nonfarm work and back-pain items relating to a 9-month
period. RESULTS: The prevalence of severe back pain was 15.7% among farmworkers
and 12.4% among nonworkers. The prevalence increased to 19.1% among farm workers
(n = 131) who also did nonfarm work. A multiple logistic regression for
farmworkers showed that significantly increased adjusted odds ratios for severe
back pain were female sex (4.59); prior accident/back injury (9.04); feeling
tense, stressed, or anxious sometimes/often (4.11); lifting/carrying heavy
objects not at work (2.98); current tobacco use (2.79); 6+ years involved in
migrant farm work (5.02); working with/around knives (3.87); and working on corn
crops (3.40). CONCLUSIONS: Areas for further research include ergonomic exposure
assessments and examining the effects of doing farm work and nonfarm work
simultaneously.
PMID- 17027294
TI - Reliability of serum assays of iron status in postmenopausal women.
AB - PURPOSE: The aim of the study is to determine the reliability during a 2-year
period of several newly developed iron-related assays to assess their potential
for use in prospective epidemiologic studies. METHODS: We assessed the temporal
reliability of several iron-related assays by using three serum samples collected
at yearly intervals from 50 postmenopausal participants in a large prospective
study. RESULTS: We observed high reliability coefficients for ferritin (0.78; 95%
confidence interval [CI], 0.67-0.86), soluble transferrin receptor (sTfR; 0.79;
95% CI, 0.69-0.87), sTfR/ferritin ratio (0.74; 95% CI, 0.62-0.83), and hepcidin
(0.89; 95% CI, 0.84-0.94). In a subset of 30 women, lower reliability was
observed for serum iron (0.50; 95% CI, 0.29-0.70), unsaturated iron-binding
capacity (0.55; 95% CI, 0.34-0.73), total iron-binding capacity (0.60; 95% CI,
0.40-0.76), and serum transferrin saturation rate (0.44; 95% CI, 0.22-0.65). The
reliability of anti-5-hydroxymethyl-2'-deoxyuridine autoantibody titers, a
biomarker of oxidized DNA damage, one of the mechanisms by which iron is thought
to impact disease risk, was very high (0.97, 95% CI, 0.5-0.99). CONCLUSIONS: Our
results show that some newly developed iron-related assays could be useful tools
to assess iron-disease associations in prospective cohorts that collect a single
blood sample.
PMID- 17027296
TI - Cross-sectional and prospective associations between passive smoking and
respiratory symptoms at the workplace.
AB - PURPOSE: The purpose of the study is to investigate the cross-sectional and
prospective relation between workplace secondhand smoke (SHS) exposure and
respiratory symptoms. METHODS: Cross-sectional data for workplace SHS exposure
and respiratory symptoms were collected by using random digit dialing from 7336
never-smoking Hong Kong workers 15 years or older in 1997 to 1998. In the 2000 to
2001 follow-up, 2213 workers who remained never smoking, had the same SHS
exposure status, worked at the same job for at least 2 years, and were not
exposed to SHS at home at follow-up were included for prospective analysis.
RESULTS: Cross-sectionally, SHS was associated significantly with frequent colds,
cough and phlegm, throat problems, and the presence of any respiratory symptoms
with adjusted odds ratios of 1.89 (95% confidence interval [CI], 1.66-2.15), 1.65
(95% CI, 1.35-2.02), 1.88 (95% CI, 1.63-2.15), and 1.96 (95% CI, 1.75-2.20) at
baseline, each having significant linear associations with duration of exposure.
SHS was not associated with rhinitis. Prospectively, consistent SHS exposure
increased the risk for cough and phlegm and any respiratory symptoms by 48% (12%
to 97%) and 54% (13% to 109%), respectively. CONCLUSIONS: This first non-Western
population-based prospective study shows that workplace SHS exposure is
associated significantly with frequent respiratory symptoms, both cross
sectionally and prospectively, thus providing strong evidence that the
association is causal.
PMID- 17027297
TI - First- and third-person approaches in implicit learning research.
AB - How do we find out whether someone is conscious of some information or not? A
simple answer is "We just ask them"! However, things are not so simple. Here, we
review recent developments in the use of subjective and objective methods in
implicit learning research and discuss the highly complex methodological problems
that their use raises in the domain.
PMID- 17027298
TI - CD8alpha+ dendritic cells are required for efficient entry of Listeria
monocytogenes into the spleen.
AB - In addition to their bridging function between innate and adaptive immunity,
dendritic cells (DCs) may also contribute to primary resistance against
infection. Here we analyzed the role of DCs during infection with Listeria
monocytogenes by performing systemic in vivo depletion of these cells. We showed
that CD8alpha(+) DCs were crucial for L. monocytogenes spreading and
proliferation in the spleen. Efficient and rapid uptake of L. monocytogenes by
CD8alpha(+) DCs required the small GTPase Rac1 and is a general characteristic of
this DC subpopulation in filtering particles out of the blood. Thus, CD8alpha(+)
DCs appear to play an important role for efficient bacterial entry into the
spleen, which is of relevance for subsequent immune responses.
PMID- 17027299
TI - Innate immune activation and CD4+ T cell priming during respiratory fungal
infection.
AB - Aspergillus fumigatus is a mold that causes a spectrum of diseases, including
lethal lung infections in immunocompromised humans and allergic asthma in atopic
individuals. T helper 1 (Th1) CD4(+) T cells protect against invasive A.
fumigatus infections whereas Th2 CD4(+) T cells exacerbate asthma upon inhalation
of A. fumigatus spores. Herein, we demonstrate that A. fumigatus-specific T cells
were rapidly primed in lymph nodes draining the lung and fully differentiated
into interferon-gamma (IFN-gamma)-producing Th1 CD4(+) T cells upon arrival in
the airways. T-bet induction in A. fumigatus-specific CD4(+) T cells was enhanced
by MyD88-mediated signals in draining lymph nodes, but T cell proliferation,
trafficking, and Th1 differentiation in the airways were Toll-like receptor (TLR)
and MyD88 independent. Our studies demonstrate that CD4(+) T cell differentiation
during respiratory fungal infection occurs incrementally, with TLR-mediated
signals in the lymph node enhancing the potential for IFN-gamma production
whereas MyD88-independent signals promote Th1 differentiation in the lung.
PMID- 17027301
TI - Letter to the editor re: "Preoperative radiological assessment for vascular
access". Eur J Vasc Endovasc Surg 2006;31:64-69.
PMID- 17027300
TI - A role for the endoplasmic reticulum protein retrotranslocation machinery during
crosspresentation by dendritic cells.
AB - Crosspresentation of exogenous antigens (Ags) to CD8(+) T cells by dendritic
cells generally requires their entry into the cytosol. Here we show that both
soluble and phagocytosed extracellular Ags accessed the cytosol via molecular
components required for endoplasmic reticulum (ER)-associated degradation (ERAD).
Exogenous Pseudomonas aeruginosa Exotoxin A, which inhibits protein translocation
from the ER to the cytosol, abrogated crosspresentation. Exotoxin A also
prevented the transporter associated with antigen processing (TAP) inhibitor,
ICP47, from entering the cytosol and blocking TAP-mediated peptide transport. In
an in vitro model of retrotranslocation, the AAA ATPase p97, an enzyme critical
for ERAD, was the only cytosolic cofactor required for protein export from
isolated phagosomes. Functional p97 was also required for crosspresentation but
not conventional presentation. Thus, crosspresentation appears to result from an
adaptation of the retrotranslocation mechanisms involved in the degradation of
misfolded ER proteins.
PMID- 17027302
TI - Medical optimisation can reduce morbidity and mortality associated with elective
aortic aneurysm repair.
AB - OBJECTIVES: Patients with aortic aneurysms have significant comorbidities which
influence outcome. Our practice includes comprehensive assessment to identify
comorbidities, allowing subsequent medical optimisation prior to aneurysm repair.
The aim of this study was to assess this process and to identify any factors
predictive of outcome. DESIGN: Prospective observational study. MATERIALS:
Medical case notes of 200 patients referred with aortic pathology. METHODS: Data
analysed included preoperative, perioperative and postoperative factors. Multiple
logistic regression analysis was performed to identify predictors of outcome.
RESULTS: Following assessment 17 patients (8.5%) were found to be unfit for
intervention and 165 patients (82.5%) proceeded to aneurysm repair. In this group
assessment uncovered previously undiagnosed cardiac, respiratory and renal
comorbidity in 19%, 57% and 29% of patients respectively. Multiple logistic
regression analysis indicated that optimisation by a renal physician reduced post
operative renal impairment (OR 0.12, 95% CI 0.03-0.45, P=0.002) while
optimisation by a cardiologist reduced respiratory complications (OR 0.7, 95% CI
0.05-0.99, P=0.049). An abnormal echocardiogram was associated with pneumonia (OR
6.9, 95% CI 1.6-29, P=0.01) and death (OR 7.9, 95% CI 1.15-54, P=0.036).
CONCLUSION: Pre-operative assessment identifies previously undiagnosed
comorbidity in a significant proportion of patients. Subsequent medical
optimisation may reduce post-operative morbidity and mortality.
PMID- 17027303
TI - Getting a grip on strangles.
PMID- 17027304
TI - Home truths about scientific truth.
PMID- 17027305
TI - Anisotropic diffusion of metabolites in peripheral nerve using diffusion weighted
magnetic resonance spectroscopy at ultra-high field.
AB - Although the diffusivity and anisotropy of water has been investigated thoroughly
in ordered axonal systems (i.e., nervous tissue), there have been very few
studies on the directional dependence of diffusion of metabolites. In this study,
the mean apparent diffusion coefficient (Trace/3 ADC) and fractional anisotropy
(FA) values of the intracellular metabolites N-acetyl aspartate (NAA), creatine
and phosphocreatine (tCr), choline (Cho), taurine (Tau), and glutamate and
glutamine (Glx) were measured parallel and perpendicular to the length of excised
frog sciatic nerve using a water suppressed, diffusion-weighted, spin-echo pulse
sequence at 18.8T. The degree of anisotropy (FA) of NAA (0.41+/-0.09) was
determined to be less than tCr (0.59+/-0.07) and Cho (0.61+/-0.11), which is
consistent with previously reported human studies of white matter. In contrast,
Glx diffusion was found to be almost isotropic with an FA value of 0.20+/-0.06.
The differences of FA between the metabolites is most likely due to their
differing micro-environments and could be beneficial as an indicator of
compartment specific changes with disease, information not readily available with
water diffusion.
PMID- 17027306
TI - A field-sweep/field-lock system for superconducting magnets--Application to high
field EPR.
AB - We describe a field-lock/field-sweep system for the use in superconducting
magnets. The system is based on a commercially available field mapping unit and a
custom designed broad-band 1H NMR probe. The NMR signal of a small water sample
is used in a feedback loop to set and control the magnetic field to high
accuracy. The current instrumental configuration allows field sweeps of +/-0.4 T
and a resolution of up to 10(-5) T (0.1 G) and the performance of the system is
demonstrated in a high-field electron paramagnetic resonance (EPR) application.
The system should also be of utility in other experiments requiring precise and
reproducible sweeps of the magnetic field such as DNP, ENDOR or PELDOR.
PMID- 17027307
TI - HMQC and refocused-INEPT experiments involving half-integer quadrupolar nuclei in
solids.
AB - Hetero-nuclear coherence transfers in HMQC and refocused-INEPT experiments
involving half-integer quadrupolar nuclei in solids are analyzed. 1D and 2D
schemes are considered under MAS for the general case of multi-spin systems SI(n)
(n4), where S is an observed nucleus. These results are also discussed in the
context of high-resolution schemes featuring MQMAS or STMAS. The theoretical
predictions are verified experimentally in a series of 1D and 2D experiments
performed at 9.4 and 18.8T.
PMID- 17027308
TI - Three-dimensional through-bond homonuclear-heteronuclear correlation experiments
for quadrupolar nuclei in solid-state NMR applied to (27)Al-O-(31)P-O-(27)Al
networks.
AB - We present here the first 3D homonuclear/heteronuclear correlation experiment
applied to quadrupolar nuclei and making use of the sole scalar J-coupling. This
experiment, based on the 2D-Homonuclear-Heteronuclear Single Quantum Correlation
(H-HSQC) experiment, uses a relayed transfer from the (27)Al central transition
to neighbouring (31)P spins and to the central transition of a second (27)Al. It
confirms the correlation map characterizing the two (27)Al and the (31)P NMR
signatures of (27)Al-O-(31)P-O-(27)Al chemically bonded molecular motifs.
PMID- 17027309
TI - Towards understanding the mechanism of action of the multidrug resistance-linked
half-ABC transporter ABCG2: a molecular modeling study.
AB - The ATP-binding cassette protein ABCG2 is a member of a broad family of ABC
transporters with potential clinical importance as a mediator of multidrug
resistance. We carried out a homology and knowledge-based, and mutationally
improved molecular modeling study to establish a much needed structural framework
for the protein, which could serve as guidance for further genetic, biochemical,
and structural analyses. Based on homology with known structures of both full
length and nucleotide-binding domains (NBD) of ABC transporters and structural
knowledge of integral membrane proteins, an initial model of ABCG2 was
established. Subsequent refinement to conform to the lipophilic index
distributions in the transmembrane domain (TMD) and to the results of site
directed mutagenesis experiments led to an improved model. The complete ABCG2
model consists of two identical subunits facing each other in a closed
conformation. The dimeric interface in the nucleotide-binding domain (NBD)
involves a characteristic nucleotide sandwich and the interface in the TMD
consists of the TM helices 1-3 of one subunit and the helices 5 and 6 of the
other. The interface between the NBD and the TMD is bridged by the conserved
structural motif between TM2 and TM3, the intracellular domain 1 (ICD1), and the
terminal beta-strand (S6) of the central beta-sheet in the NBD. The apparent
flexibility of the ICD1 may play a role in transmitting conformational changes
from the NBD to the TMD or from the TMD to the NBD.
PMID- 17027310
TI - Genetic mutation profile of isovaleric acidemia patients in Taiwan.
AB - Isovaleric acidemia (IVA), a rare recessive autosomal disorder, is caused by
isovaleryl-CoA dehydrogenase (IVD) deficiency. IVA may present with symptoms
during the acute stage of severe metabolic acidosis, ketosis, vomiting, and
altered mental status. With the help of newborn screening (NBS) by tandem mass
spectrometry (MS/MS), IVA can now be diagnosed presymptomatically. According to
statistic data, the incidence of IVA in Taiwan was about 1/365,000. In this
study, six IVA patients from five families were investigated and followed-up
clinically. As for the timing, two patients were found before MS technique
introduced to Taiwan, the others were identified after MS/MS applied to NBS. The
blood level of C5-carnitine in our patients was 7.43-18.96 microM (with upper
limit in our laboratory <0.51 microM) and all of their urines contained raised
amounts of 3-hydroxyisovaleric acid and isovalerylglycine. Molecular analysis of
their IVD gene revealed six mutation profiles, among which the 149G-->A
(Arg21His) and 1174 C-->T (Arg363Cys) mutations have been reported previously,
while the other four mutations, 386A-->G (His100Arg), 347C-->T (Ser87Phe), 1007G-
>A (Cys307Tyr) and 1199A-->G (Tyr371Cys), were first reported. Specially, we
found 1199A-->G (Tyr371Cys) mutated was a common recurring missense mutation in
our population (4 in 10 mutant alleles).
PMID- 17027311
TI - Molecular analysis of HPRT deficiencies: an update of the spectrum of Asian
mutations with novel mutations.
AB - Inherited mutations of a purine salvage enzyme, hypoxanthine guanine
phosphoribosyltransferase (HPRT, EC 2.4.2.8), give rise to Lesch-Nyhan syndrome
or HPRT-related gout. We have identified a number of HPRT mutations in Asian
patients manifesting different clinical phenotypes, by analyzing all nine exons
of the HPRT gene (HPRT1) from genomic DNA and reverse-transcribed mRNA using the
PCR technique coupled with direct sequencing. In this study, we update the
spectrum of mutations with nine novel mutations. Two missense mutations (T124P
and D185G) were detected in patients with HRH (HPRT-related hyperuricemia). In a
patient having a severe partial deficiency of HPRT with neurological dysfunction
(HRND: HPRT-related neurological dysfunction), a single nucleotide substitution
(27+5G > A) causing a splicing error was found in intron 1. The mutation resulted
in a remarkably decreased level of normal mRNA, and production of an abnormal
mRNA with a 49-bp insert at the 5'-end of intron 1, which caused the frame-shift
of an amino acid codon (10fs27X). In six typical Lesch-Nyhan families, we found
two 3-bp deletions responsible for single amino acid deletions (V8del and
Y28del), two 1-bp deletions (440delA and 635delG) generating a frame-shift, an
insertion of two amino acids (159insKV), and a 4,131-bp deletion from introns 4
to 6 resulting in two types of abnormal mRNA. Including these nine mutations, 42
HPRT1 mutations have been identified among 47 Asian families with deficiency of
HPRT.
PMID- 17027312
TI - [Valorisation of high technology radiotherapy in Europe].
AB - In order to support adoption and dissemination into clinical practice of
innovative treatment strategies, being almost by definition more expensive than
the corresponding standard treatments, an appropriate reimbursement is a
prerequisite. This article describes different possible financing systems in the
context of technological advances in radiation oncology and analyses if and how
the reimbursement issue has been tackled in European radiotherapy centres.
PMID- 17027313
TI - Sexual differences in Turkish dentition.
AB - Sexual variation in the human skeleton and dentition is of great concern for both
anthropologists and odontologists. Assessment of variation in dental size gives a
clue about the behavior of a population, and also differences between the sexes.
This study deals with sexual differences in a Turkish sample of individuals
ranging in age from 20 to 29 years. The sample is composed of 28 buccolingual
(BL) and mesiodistal (MD) dimensions of upper and lower dentition (I1 through
M2). Dental casts of 50 males and 50 females were analyzed using discriminant
function statistics. The results indicated that 8 of the upper and 7 of the lower
dimensions were significantly greater in males. Many of the differences were
located in the anterior teeth of both jaws. In a stepwise function applied to
both arches, the lower and upper canine BL, lower canine and P1 MD, and lower I2
BL were used as the most discriminating variables. When the front teeth (i.e.,
I1, I2, and C) are used in separate functions, only the canine BL of the lower
jaw and I2 and C BL of the upper jaw were found to have the discriminating
variables. Classification accuracy was 81% for the total sample, 76% for upper
front and 81% for lower front teeth. In conclusion, dentition in Turkish people
seems to be less sexually dimorphic than the populations with which they were
compared (Jordanians, Swedish and South Africans) as was determined by the
percent of accuracy obtained. In comparison with other populations, as
anticipated, Turkish dental size is closest to the Jordanian sample and farthest
from the South African whites.
PMID- 17027314
TI - Application of salicylic acid dosimetry to evaluate hydrodynamic cavitation as an
advanced oxidation process.
AB - The generation of OH* radicals inside hydrodynamic cavitation bubbles was
monitored using a salicylic acid dosimeter. The reaction of this scavenger with
OH* produces 2,5-dihydroxybenzoic acid (2,5-DHB) and, to a lesser degree, 2,3
DHB. The former, is a specific reaction product that can be determined with a
very high sensitivity using HPLC-IF. This method has been applied to study the
influence of the flow-rate and the solution pH for a given cavitation chamber
geometry. The salicylic dosimetry has proven especially suitable for the
characteristic time scales of hydrodynamic cavitation (higher than those of
ultrasonic cavitation), which usually gives rise to recombination of radicals
before they can reach the liquid-phase. Working at low pH the hydrophobic
salicylic acid migrates to the gas-liquid interface and reacts with the OH*
radicals, increasing the trapping efficiency of the dosimeter. Hydrodynamic
cavitation works as a very low frequency sonochemical reactor, and therefore its
potential as an Advanced Oxidation Process might be limited to reactions at the
gas-liquid interface and inner bubble (i.e. with volatiles and/or hydrophobic
substances).
PMID- 17027315
TI - Development of a novel articulator that reproduced jaw movement with six-degree
of-freedom.
AB - A novel robotic articulator that reproduced a six-degree-of-freedom jaw movement
was developed and tested. A precise six-axis micro-positioning stage was employed
for this articulator. A high-resolution jaw-tracking device measured the
functional jaw movement of the patient and a six-axis micro-positioning stage
reproduced recorded jaw movement data. A full veneer crown restoration was
fabricated with this articulator system. A working cast was mounted on the
positioning stage of the articulator. An occlusal table with soft wax was
attached on the cast tooth die, and the jaw movements were reproduced to create a
functionally generated path on the occlusal table. The finished occlusal record
was used to obtain the wax pattern for the crown. In this subject, no intra-oral
occlusal adjustment was necessary for setting the finished full veneer crown.
Since this articulator could perform a precise reproduction of the dynamic jaw
motion during the functional jaw movement, this system has potential to improve
accuracy of the prosthetic teeth occlusion.
PMID- 17027316
TI - The development and practice of forensic podiatry.
AB - Forensic podiatry is a small, but potentially useful specialty using clinical
podiatric knowledge for the purpose of person identification. The practice of
forensic podiatry began in the early 1970s in Canada and the UK, although
supportive research commenced later in the 1990s. Techniques of forensic podiatry
include identification from podiatry records, the human footprint, footwear, and
the analysis of gait forms captured on Closed Circuit Television Cameras. The
most valuable techniques relate to the comparison of the foot impressions inside
shoes. Tools to describe, measure and compare foot impressions with footwear wear
marks have been developed through research with potential for further
development. The role of forensic podiatrists is of particular value when dealing
with variable factors relating to the functioning and the shod foot. Case studies
demonstrate the approach of podiatrists, in footwear identification, when
comparing exemplar with questioned foot impressions. Forensic podiatry practice
should be approached cautiously and it is essential for podiatrists undertaking
this type of work to understand the context within which the process of person
identification takes place.
PMID- 17027317
TI - Agricultural and horticultural pesticides fatal poisoning; the Jordanian
experience 1999-2002.
AB - A prospective autopsy study addressing fatal poisoning with agricultural and
horticultural pesticides was undertaken in Jordan over a 4 year period. A total
number of 140 deaths occurred during 1999-2002. The mean fatality rate was 0.68
case per 100,000 population and the age range was 2-55 years; mean 28.3 years
with male to female ratio 1.03. The largest number of cases occurred in those 20
29 years (n=69, 49.3%) followed by the age group 30-39 years (n=34, 24.3%) and 40
49 years (n=17, 12.1%). Less than 3.0% of the total fatal poisoning was noticed
in both children younger than 9 years of age and those in the age group 50-59
years, with no fatal poisoning in adults at the age 60 years and above. At least
64.3% of all pesticide fatalities were due to suicide with male: female ratio
(1.37:1). Accidental and homicide poisoning resulted in 24.3% and 7.9% of the
total fatalities, respectively; however, only five cases 3.6% of fatal poisoning
were due to unknown pesticides. The main pesticide used was carbamates with 110
cases 78.6% followed by organophosphorus 23 cases 16.4%. The study showed that
the present legislation on pesticides availability in Jordan failed to reduce the
number of fatal pesticides poisoning since the number of fatal pesticides
poisoning was increased from 25.3 to 35 cases per year over a 20 years period.
Enforcement of a new legislation addressing the availability of agricultural and
horticultural pesticides for self-harm, especially carbamates and
organophosphorus, is the most important strategy in the long term to prevent
fatal pesticides poisoning in Jordan.
PMID- 17027318
TI - Fatal asphyxia by a thyroglossal duct cyst in an adult.
AB - Thyroglossal duct cysts arise from remnants of embryonic thyroglossal duct that
connects the foramen cecum at the base of the tongue to the thyroid gland. The
remnants enlarge secondary to secretions from the epithelial lining. Usually,
thyroglossal cysts present as non-tender masses. However, they may also become
infected, produce fistulas or give hoarseness and dysphagia. Rarely, especially
if the mass is located at the base of the tongue, airway obstruction and dyspnea
can ensue. This unusual presentation has been mainly seen in very young children
and has caused death in about half of these cases. Nevertheless, in the adult
population, very few cases of airway obstruction by thyroglossal duct cysts have
been reported, only one being fatal. We present the case of a 55-year-old man who
died from fatal asphyxia caused by a thyroglossal cyst.
PMID- 17027319
TI - Delayed deaths after vascular traumatism: two cases.
AB - During expert testimony in court, forensic pathologists are often asked to
estimate the length of survival following fatal injuries. Though it is impossible
to be precise, fatal vascular trauma survival times are generally considered
short. We here report two unusual cases of delayed deaths, one following
homicidal stabbing of the heart and the other by suicidal cutting of the neck. In
those two cases, investigation clearly provided evidence of prolonged survival:
slightly more than 2h for the first case and about 8h for the second. Relevant
literature is revised and physiopathological hypotheses are discussed.
PMID- 17027320
TI - Macrophage activation syndrome: an autopsy case of sudden death.
AB - In a context of viral gastroenteritis, we report an unusual case of sudden death
in an 8-year-old child. The only macroscopic abnormality observed in the autopsy
was a diffuse mesenteric adenitis. Organ samples were taken for histopathological
examination and a diffuse lymphocytic infiltration was observed. A sinusoidal
histiocytic hyperplasia was found in the lymph nodes. Microscopic examination of
the lungs and the lymph nodes revealed haemophagocytic lesions (lymphocytes
within the cytoplasm of histiocytic macrophages). Immunohistochemical studies
demonstrated that the histiocytes were CD68+ PS100- CD1A-. Following this
microscopic examination macrophage activation or haemophagocytic syndrome was
diagnosed. The syndrome is a distinct clinical entity characterised by fever,
pancytopaenia, splenomegaly, and haemophagocytosis in the bone marrow, liver and
lymph nodes. It is a clinical entity that is very difficult to diagnose due to
the lack of specific clinical signs. It is generally a complication of an
infectious process, an aggravation of an auto-immune disease or a complication of
a neoplastic process. The physiopathology involves a disregulation of T
lymphocytes and particularly T helper lymphocytes. To make this diagnosis the
anatomopathological examination must be performed by an experienced practitioner.
The presence of a lymphocyte infiltrate of macrophagic histiocytes in myeloid
organs and especially positive CD68+ immune markers are the anatomopathological
proofs of diagnosis. The autopsy examination must be carefully performed and
include systematic sample harvesting for anatomopathological examination. The
results of all these examinations taken together allow the diagnosis of
haemophagocytic syndrome to be finally made.
PMID- 17027321
TI - Children and adolescents victimized by sexual abuse in the city of Rio de
Janeiro: an appraisal of cases.
AB - Physical and/or sexual abuse, negligence, and psychological abuse against
children and adolescents, constitute a socially important syndrome, demanding
preventive public policies and rules for its eradication. Sexual abuse, as a
troublesome occurrence, or even its mere presumption, does not regularly undergo
official notification. We have examined legal investigative registers at the
Instituto Medico-Legal do Rio de Janeiro - Sede set up from January to March
2000, including women, children and adolescents, with medico-legal histories
suggestive of sexual assault. From a sample of 1419 cases, we selected those
involving vaginal coitus or other libidinous practices, with an upper age limit
of 17 years, reducing our sample to 44 subjects. 84.09% of the assaults occurred
between ages 0 and 14 years. In 62.36% of the studied cases there was no mention
about perpetrators. Material for laboratory researches had not been collected in
84.09% of the cases. There is any lesions in 70.45% of the sample.
PMID- 17027322
TI - Sudden cardiac death associates with a large right atrium thrombus in a late
survivor of heart transplantation.
AB - A fatal circulatory collapse developed acutely in a patient six years after
orthotopic heart transplantation. Autopsy revealed a large, fresh thrombus inside
the right atrium which obstructed the orifice of the vena cava completely. The
grafted coronary artery and pulmonary vessels were patent. There was no rejection
or acute infarct in myocardium. Mildly immature organization was seen on the
thrombus-adhered wall. Four chamber enlargement and a rapid decline of right
ventricular hypokinesia were detected shortly before death although he did not
show active cardiopulmonary symptom. Intracardiac thrombus formation is rather
uncommon in late survivor. A synergic effect of atrial turbulence and ventricular
hypokinesia in the right heart, superimposed by tissue organization, was proposed
for thrombus formation. An empty cardiac output was favored for his mortality.
These findings provide a strong evidence to suggest anticoagulation in case of
complicated or highly risk of embolization such as turbulence or hypokinesia
despite of an absence of active cardiopulmonary symptom.
PMID- 17027323
TI - Cerebellar-pulmonary embolism, cause of death in the newborn.
AB - A 28-year-old woman delivered twin girls. The first twin was delivered without
any difficulty. The head of the second twin failed to descend with pushing. A
special kind of obstetrical forceps, Thierry's spatulas, were used to extract the
second twin in the occipito-posterior vertex position. She was declared dead
after recording Apgar scores of 0 and 0 and after 35 min of resuscitation. An
autopsy was performed for medico-legal reasons. Macroscopic examination of the
brain showed a small area of leptomeningeal haemorrhage in the left sylvian fossa
and the base of the brain. Histopathological studies demonstrated cerebellar
tissue emboli in meningeal and pulmonary arteries. Excessive pressure on the
suboccipital region during delivery can cause traumatic separation of the
occipital chondral junctions, which may lead to separation of the occipital
squama from lateral parts of the occipital bones. The inferior part of the
occipital squama is displaced forward and upward into the posterior fossa. This
produces tearing of the duramater and occipital sinuses leading to leptomeningeal
haemorrhage in the posterior cranial fossa, often associated with cerebellar
lesions. Major stretching and tearing of the posterior aspect of tentorium
cerebelli in contact with the sinuses and the cerebellar cortex may also occur,
inducing slight movement of the occipital bones and subsequent emboli. This case
study is that of a newborn death due to pulmonary cerebellar tissue embolism
occurring during delivery with Thierry's forceps, which are considered less
traumatic to the foetal cranium. A review of the literature identified 17 other
published cases. In difficult deliveries this pathology should sought carefully.
Brain, lung and placenta tissue sections must be studied.
PMID- 17027324
TI - New views of S-RNase-based self-incompatibility.
AB - S-RNase-based self-incompatibility (SI) is the most widespread form of
genetically controlled mate selection in plants. S-RNase controls pollination
specificity in the pistil, while the newly discovered SLF/SFB controls
pollination specificity in the pollen. A widely discussed model suggests that
compatibility is explained by ubiquitylation and degradation of nonself-S-RNase
and that, conversely, incompatibility is caused by failure to degrade self-S
RNase. This model is consistent with the long-standing view that S-RNase
inhibition is central to SI. Recent results show, however, that S-RNase is
compartmentalized in pollen tubes and, significantly, that compatibility might
not require SLF/SFB. S-RNase compartmentalization and dislocation into the pollen
tube cytoplasm might be similar to the trafficking of other cytotoxins such as
ricin.
PMID- 17027325
TI - Mutagenic and carcinogenic potential of a textile azo dye processing plant
effluent that impacts a drinking water source.
AB - Recently a textile azo dye processing plant effluent was identified as one of the
sources of mutagenic activity detected in the Cristais River, a drinking water
source in Brazil [G.A. Umbuzeiro, D.A. Roubicek, C.M. Rech, M.I.Z. Sato, L.D.
Claxton, Investigating the sources of the mutagenic activity found in a river
using the Salmonella assay and different water extraction procedures, Chemosphere
54 (2004) 1589-1597]. Besides presenting high mutagenic activity in the
Salmonella/microsome assay, the mutagenic nitro-aminoazobenzenes dyes CI Disperse
Blue 373, CI Disperse Violet 93, and CI Disperse Orange 37 [G.A. Umbuzeiro, H.S.
Freeman, S.H. Warren, D.P. Oliveira, Y. Terao, T. Watanabe, L.D. Claxton, The
contribution of azo dyes in the mutagenic activity of the Cristais river,
Chemosphere 60 (2005) 55-64] as well as benzidine, a known carcinogenic compound
[T.M. Mazzo, A.A. Saczk, G.A. Umbuzeiro, M.V.B. Zanoni, Analysis of aromatic
amines in surface waters receiving wastewater from textile industry by liquid
chromatographic with eletrochemical detection, Anal. Lett., in press] were found
in this effluent. After approximately 6 km from the discharge of this effluent, a
drinking water treatment plant treats and distributes the water to a population
of approximate 60,000. As shown previously, the mutagens in the DWTP intake water
are not completely removed by the treatment. The water used for human consumption
presented mutagenic activity related to nitro-aromatics and aromatic amines
compounds probably derived from the cited textile processing plant effluent
discharge [G.A. Umbuzeiro, D.A. Roubicek, C.M. Rech, M.I.Z. Sato, L.D. Claxton,
Investigating the sources of the mutagenic activity found in a river using the
Salmonella assay and different water extraction procedures, Chemosphere 54 (2004)
1589-1597; G.A. Umbuzeiro, H.S. Freeman, S.H. Warren, D.P. Oliveira, Y. Terao, T.
Watanabe, L.D. Claxton, The contribution of azo dyes in the mutagenic activity of
the Cristais river, Chemosphere 60 (2005) 55-64]. Therefore, it is important to
evaluate the possible risks involved in the human consumption of this
contaminated water. With that objective, one sample of the cited industrial
effluent was tested for carcinogenicity in the aberrant crypt foci medium-term
assay in colon of Wistar rats. The rats received the effluent in natura through
drinking water at concentrations of 0.1%, 1%, and 10%. The effluent mutagenicity
was also confirmed in the Salmonella/microsome assay with the strains TA98 and
YG1041. There was an increased number of preneoplastic lesions in the colon of
rats exposed to concentrations of 1% and 10% of the effluent, and a positive
response for both Salmonella strains tested. These results indicate that the
discharge of the effluent should be avoided in waters used for human consumption
and show the sensitivity of the ACF crypt foci assay as an important tool to
evaluate the carcinogenic potential of environmental complex mixtures.
PMID- 17027326
TI - Identification of the rosasite group minerals--an application of near infrared
spectroscopy.
AB - The ability of near infrared reflectance spectroscopy to classify the rosasite
group minerals from spectral characteristics is demonstrated. NIR spectroscopy
can be regarded as an alternative tool for structure analysis. The spectra show
that rosasite group minerals with different cations can be distinguished. Ni2+ in
nullaginite [Ni2(CO3)(OH)2] is conspicuous through a single broad band absorption
feature at 8525 cm-1, extended from 11,000 to 7000 cm-1. The effect of Ni on Cu
is seen in the spectrum of glaukosphaerite [(Cu, Ni)2(CO3)(OH)2] both by a red
shift of the spectrum and reduction in intensity of bands with variable positions
of band maxima for Cu2+ at 6995 cm-1 and Ni2+ at 7865 cm-1. The spectrum of
rosasite [(Cu, Zn)2(CO)3(OH)2] is characterised by Cu2+ band at 7535 cm-1.
Kolwezite [(Cu, Co)2(CO)3(OH)2] is a spectral mixture of Cu and Co but optically
separated by Co2+ and Cu2+ peaks at 8385 and 7520 cm-1. Vibrational spectra of
carbonates show a number of bands in the 7000-4000 cm-1 region attributable to
overtones, combination of OH stretching and deformation modes. They appear to be
uniform in nature since the structure of rosasite group minerals is identical.
The complexity of these features varies between samples because of the variation
in composition and hence is useful for discriminating different hydrous
carbonates.
PMID- 17027327
TI - Fluorescence properties of Nd3+-doped tellurite glasses.
AB - The compositional and concentration dependence of luminescence of the (4)F(3/2)-
>(4)I(J) (J=13/2, 11/2 and 9/2) transitions in four Nd(3+)-doped tellurite based
glasses has been studied. The free-ion energy levels obtained for
60TeO(2)+39ZnO(2)+1.0Nd(2)O(3) (TZN10) glass have been analysed using the free
ion Hamiltonian model and compared with similar results obtained for Nd(3+):glass
systems. The absorption spectrum of TZN10 glass has been analysed using the Judd
Ofelt theory. Relatively longer decay rates have been obtained for Nd(3+)-doped
phosphotellurite glasses. The emission characteristics of the (4)F(3/2)-
>(4)I(11/2) transition, of the Nd(3+):TZN10 glass, are found to be comparable to
those obtained for Nd(3+):phosphate laser glasses. The non-exponential shape of
the emission decay curves for the (4)F(3/2)-->(4)I(11/2) transition is attributed
to the presence of energy transfer processes between the Nd(3+) ions.
PMID- 17027328
TI - Promoter analysis of the murine squalene epoxidase gene. Identification of a 205
bp homing region regulated by both SREBP'S and NF-Y.
AB - Squalene epoxidase (SE) is one of the most highly regulated enzymes of the
cholesterol biosynthesis pathway. Here we identify the molecular basis for SREBP
2 synergy with NF-Y as the prime regulator of SE gene transcription. As expected
cholesterol markedly suppressed transcriptional activity, while SREBP-1a, -1c and
-2 activated it. Knock down of SREBP-2 mRNA resulted in an 85% reduction in SE
expression. Interspecies comparison of SE promoter sequences identified two
conserved putative NF-Y sites that were found to be important for maximal SREBP
dependent gene activation and one novel conserved sterol response element (SRE).
Altogether three novel SREs were identified within a 205 bp region of the SE
promoter. Each of the SREs was capable of binding SREBP-2 but mutation of all
three, singly or in combination, did not completely eliminate the SREBP response.
Our results demonstrate the critical dependence of this 205 bp region for sterol
dependent regulation of SE and uncover a possible framework for SREBP-promoter
interaction, including a potent synergy with NF-Y that may be of principal
importance.
PMID- 17027329
TI - Prolonged effect of single carnitine administration on fasted carnitine-deficient
JVS mice regarding their locomotor activity and energy expenditure.
AB - Carnitine is an essential cofactor for the oxidation of fatty acid in the
mitochondria and an efficient therapeutics for primary carnitine deficiency. We
herein analyzed the prolonged effects of carnitine on the reduced locomotor
activity and energy metabolism of fasted carnitine-deficient juvenile visceral
steatosis (jvs(-/-)) mice. We found that a single carnitine administration to 24
h fasted jvs(-/-) mice in the morning increased both the locomotor activity and
oxygen consumption at night not only on the same day, but also on the next day,
when the carnitine levels in the blood and tissues were already as low as at the
original carnitine-deficient state. We also found that fat utilization for energy
production significantly increased under fasting even in jvs(-/-) mice and was
stimulated in the carnitine-administrated fasted jvs(-/-) mice at night, in
comparison to that observed in the saline-administered jvs(-/-) mice, at least
for 2 days even under the low plasma and tissue carnitine levels. These results
suggest that the low tissue carnitine levels are therefore not the sole rate
limiting factor of general fatty acid oxidation in carnitine-deficient jvs(-/-)
mice.
PMID- 17027330
TI - Prevalence and prognostic significance of atrial fibrillation in outpatients with
heart failure due to left ventricular systolic dysfunction.
AB - INTRODUCTION: Atrial fibrillation (AF) is common in patients with heart failure
(HF) due to left ventricular systolic dysfunction (LVSD), with conflicting
prognostic data. The aim of our study was to assess the prevalence and incidence
of AF in patients with HF and to determine the prognostic impact of baseline AF
and the development of new onset AF. METHODS AND RESULTS: We included 1019
outpatients with HF due to LVSD; follow-up time ranged from 3 to 64 months. At
baseline 26.4% of patients had AF. Of the 284 patients with a follow-up ECG and
baseline SR, 18.7% developed new onset AF. Patients with AF were older (p<0.001),
more often male (p=0.04), and more likely to have a history of stroke (p=0.03),
but were less likely to have IHD (p<0.001). Baseline rhythm was independent of
LVEF and NYHA-class. Baseline AF was associated with increased all-cause
mortality (HR 1.38; CI 1.07-1.78, p=0.01) and all-cause mortality/hospitalisation
(HR 1.43; CI 1.22-1.68, p<0.001). When adjusted for baseline covariates, baseline
AF was independently associated with an increased risk of experiencing the
combined endpoint (HR 1.29; CI 1.05-1.58; p=0.02), but did not predict all-cause
mortality. By multivariable analyses, new-onset AF was associated with increased
risk of all-cause mortality/hospitalisation (HR 1.45; CI 1.05-2.00; p=0.02).
CONCLUSION: In outpatients with HF due to LVSD, AF is a common co-morbidity,
which adversely affects morbidity and mortality outcomes.
PMID- 17027331
TI - Pressure tracings in obstructive Tako-Tsubo cardiomyopathy.
AB - A 70-year-old female experienced severe anxiety due to an incident with a
stranger when she was home alone at night. Immediately after the event, she had
an oppressive chest sensation; 16 h later she was admitted to hospital. Left
ventriculography showed akinesia of the mid-to-distal portion and hyperkinesia of
the basal portion of the left ventricular chamber. However, coronary angiography
showed no significant coronary artery disease. We diagnosed her as having Tako
Tsubo cardiomyopathy. Subsequently, left ventricular and central aortic pressures
were recorded simultaneously. Initial recording showed a peak systolic gradient
of 60 mm Hg. On the first sinus beat after a premature ventricular contraction,
the peak systolic gradient increased to 130 mm Hg, and the pulse pressure
decreased. Shortly after intravenous administration of nitroglycerin (0.5 mg),
central aortic pressure decreased and the peak systolic gradient increased to 100
mm Hg. On the first sinus beat after a premature ventricular contraction, the
peak systolic gradient increased to 160 mm Hg, and the pulse pressure decreased.
Five minutes after intravenous nitroglycerin, the peak systolic gradient returned
to 70 mm Hg. Follow-up transthoracic echocardiography 13 days later showed normal
left ventricular wall motion with no pressure gradient through the left
ventricular outflow tract.
PMID- 17027332
TI - Don't miss extra-cardiac manifestations of familial left ventricular
hypertrabeculation/non-compaction.
PMID- 17027333
TI - Sleep-disordered breathing in patients with symptomatic heart failure: a
contemporary study of prevalence in and characteristics of 700 patients.
AB - AIM: Evaluation of the prevalence and nature of sleep-disordered breathing (SDB)
in patients with symptomatic chronic heart failure (CHF) receiving therapy
according to current guidelines. METHODS AND RESULTS: We prospectively screened
700 patients with CHF (NYHA class> or =II, LV-EF< or =40%) for SDB using
cardiorespiratory polygraphy (Embletta). Furthermore, echocardiography,
cardiopulmonary exercise and 6-min walk testing were performed. Medication
included ACE-inhibitors and/or AT1-receptor blockers in at least 94%, diuretics
in 87%, beta-blockers in 85%, digitalis in 61% and spironolactone in 62% of
patients. SDB was present in 76% of patients (40% central (CSA), 36% obstructive
sleep apnoea (OSA)). CSA patients were more symptomatic (NYHA class 2.9+/-0.5 vs.
no SDB 2.57+/-0.5 or OSA 2.57+/-0.5; p<0.05) and had a lower LV-EF (27.4+/-6.6%
vs. 29.3+/-2.6%, p<0.05) than OSA patients. Oxygen uptake (VO(2)) was lowest in
CSA patients: predicted peak VO(2) 57+/-16% vs. 64+/-18% in OSA and 63+/-17% in
no SDB, p<0.05. 6-min walking distances were 331+/-111 m in CSA, 373+/-108 m in
OSA and 377+/-118 m in no SDB (p<0.05). CONCLUSIONS: This study confirms the high
prevalence of SDB, particularly CSA in CHF patients. CSA seems to be a marker of
heart failure severity.
PMID- 17027334
TI - Prescription of beta-blockers in patients with advanced heart failure and
preserved left ventricular ejection fraction. Clinical implications and survival.
AB - BACKGROUND: The effects of beta-blockers in patients with heart failure (HF) and
preserved left ventricular ejection fraction (LVEF) are not well established.
AIMS: To assess the association between beta-blocker prescription at discharge
and mortality in a cohort of patients with advanced HF and preserved LVEF.
METHODS AND RESULTS: We prospectively studied a cohort of 443 patients with
advanced HF and preserved LVEF (LVEF> or =40%). Mean age was 78 years, 56%
female, 33% NYHA class IV. Overall, 227 patients (51%) had a beta-blocker
prescribed at discharge. Mean duration of follow-up was 25 (+/-18) months. Death
(all cause) occurred in 40 patients (17.6%) who were receiving a beta-blocker at
discharge and 73 patients (33.8%) who were not on a beta-blocker. In multivariate
Cox analysis, including adjustment for propensity score, prescription of a beta
blocker remained associated with a 43% relative mortality risk reduction (HR
0.57, 95% CI 0.37 to 0.88, p=0.01). CONCLUSIONS: In this cohort of patients with
advanced HF and preserved LVEF, prescription of a beta-blocker was associated
with a significant mortality reduction. This beneficial effect of beta-blocker
use needs to be further confirmed in prospective, randomised clinical trials.
PMID- 17027335
TI - B-type natriuretic peptide levels predict event-free survival in patients with
implantable cardioverter defibrillators.
AB - INTRODUCTION: We examined whether B-type natriuretic peptide (BNP) levels predict
outcome in heart failure patients with implantable cardioverter defibrillators
(ICD) using a combined endpoint of malignant tachyarrhythmias, death or heart
transplantation. METHODS AND RESULTS: BNP levels were measured in 123 ICD
patients with chronic heart failure (age: 63+/-12 years, ejection fraction: 29+/
10%). After a median follow-up of 25 months, the combined endpoint was reached in
28 patients (first tachyarrhythmic event, n=16; death, n=11; heart
transplantation, n=1). BNP levels were significantly lower in patients with event
free survival compared to patients reaching the combined endpoint of this study
(median: 140 vs. 373 pg/ml; p<0.001). Multivariable Cox regression analysis
revealed that BNP levels predict adverse outcome (RR 1.002 per pg/ml increment;
95% CI: 1.001-1.003; p<0.001) and use of beta-blockers was associated with
favourable outcome (RR 0.319; 95% CI 0.151-0.670; p=0.004). LV ejection fraction
(p=0.66) did not significantly predict event-free survival in multivariable
analysis. CONCLUSIONS: BNP plasma levels are useful markers to predict event-free
survival in ICD patients with heart failure. Of note, malignant tachyarrhythmias
appear responsible for about 50% of fatal outcomes. Our findings suggest that
determination of BNP plasma levels is more valuable than determining LV ejection
fraction to anticipate event-free survival in this population.
PMID- 17027336
TI - Metabolic disturbances in chronic heart failure: a case for the "macho" approach
with testosterone?!
AB - Chronic heart failure (CHF) primarily affects the cardiovascular system. In
addition, there is strong evidence that CHF is a complex metabolic disorder.
Metabolic abnormalities include insulin resistance and lack of anabolic hormone
activity. To date there have been few interventional trials targeting insulin
sensitivity. A recent study suggests a link between testosterone therapy and
improvements in insulin sensitivity, measured using the homeostatic model
assessment (HOMA-IR). We discuss this study in detail. Further studies are needed
to substantiate this link and to generally explore the value of testosterone
therapy in CHF patients.
PMID- 17027337
TI - Identification and characterization of "pathoadaptive mutations" of the cadBA
operon in several intestinal Escherichia coli.
AB - The dysenteric Shigella spp. and enteroinvasive Escherichia coli (EIEC) have
evolved from commensal E. coli by the acquisition of a virulence plasmid and
inactivation of genes of the cad locus encoding lysine decarboxylase (LDC) by so
called pathoadaptive mutation. As horizontal gene transfer and recombination
occurs frequently in E. coli we were interested to see if similar pathoadaptive
mutations are commonly present in other intestinal pathotypes. Therefore, we
examined 140 intestinal E. coli strains of various pathotypes and the ECOR
collection for their ability to decarboxylate lysine, and identified 25 strains
that were unable to do so. Complementation of a Shiga toxin-producing E. coli and
two enteropathogenic E. coli strains, both LDC-negative, with the intact cad
locus restored LDC activity and resulted in a reduction in adherence to tissue
culture cells. We investigated the cad locus for possible alterations by using
hybridization and PCR techniques and compared the results with the alterations
reported for Shigella spp. and EIEC strains. Interestingly, the alterations of
the cad genes were similar to those previously reported, pointing towards a
parallel evolution of LDC silencing in different intestinal E. coli pathotypes.
PMID- 17027338
TI - Cannabinoid receptors as therapeutic targets for obesity and metabolic diseases.
AB - One of the most interesting pharmacological targets proposed in the past ten
years for fighting obesity and related metabolic disorders is the endocannabinoid
system. The role of the endocannabinoid system is crucial in regulating the
rewarding properties of food, in controlling energy balance by acting at the
hypothalamic circuitries involved in food intake, and in peripheral metabolism by
influencing adipocytes, hepatocytes, myocytes and pancreatic endocrine cells.
Obesity seems to be a condition associated with a pathological overactivation of
the endocannabinoid system; therefore, restoring a normal endocannabinoid tone by
antagonizing the cannabinoid receptor type 1 (CB(1)) could help arrest both the
development and the maintenance of obesity.
PMID- 17027339
TI - Understanding the molecular causes of Parkinson's disease.
AB - Parkinson's disease (PD) is a neurodegenerative disease that is both common and
incurable. The majority of cases are sporadic and of unknown origin but several
genes have been identified that, when mutated, give rise to rare, familial forms
of the disease. The principal genes that have been shown to cause PD are alpha
synuclein (SNCA), parkin, leucine-rich repeat kinase 2 (LRRK2), PTEN-induced
putative kinase 1 (PINK1) and DJ-1. Here, we discuss what has been learnt from
the study of these genes and what has been elucidated of the molecular pathways
that lead to cell degeneration. Of importance is what these molecular events and
pathways tell scientists of the common sporadic form of PD. Although complete
knowledge of these genes' functions remains elusive, recent work implicates
abnormal protein accumulation, protein phosphorylation, mitochondrial dysfunction
and oxidative stress as common pathways to PD pathogenesis.
PMID- 17027341
TI - Electrical induction of spikes in the hippocampus impairs recognition capacity
and spatial memory in rats.
AB - In clinical studies, interictal EEG spikes (IS) have been associated with
numerous neuropsychological abnormalities, ranging from transitory cognitive
impairment to epileptic encephalopathies. Understanding the pathophysiological
mechanisms of IS has been hampered by the lack of validated animal models. To
mimic IS, a stimulating microelectrode was implanted in the ventral hippocampal
commissure and a recording microelectrode in the CA1 region of the hippocampus of
normal male rats. Spike patterns were induced using a series of electrical pulses
10-30 ms in duration with a frequency of 0.5-2Hz and a current of 0.2mA. The
commissural stimulation-evoked population discharges in the hippocampus resembled
naturally occurring IS in epileptic rats and, in no cases, resulted in behavioral
seizures. For behavioral testing, the Morris water maze, radial arm maze, and
object recognition tasks were used. Spikes were induced during sleep between the
two sets of water maze trials; during the trials in the radial arm maze task; and
prior to the sample phase and during the delay periods in the object recognition
task. We demonstrated that rats that received spikes took longer to reach the
escape platform in the second set of water maze trials; had significantly more
reference errors and required more trials to complete the radial arm maze task;
and had lower investigation ratios in the object recognition task. The results
indicate that induction of spikes in the hippocampus results in impairment of
spatial reference and nonspatial object recognition memory.
PMID- 17027340
TI - Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy
are normalized by impairment of brain corticotropin-releasing factor.
AB - Social interaction phenotyping is an unexplored niche in animal modeling of
epilepsy despite the sensitivity of affiliative behaviors to emotionality and
stress, which are known seizure triggers. Thus, the present studies examined the
social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in
untreated animals and following preexposure to a handling stressor. The second
aim of the present studies was to evaluate the dependence of sociability in El
mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor
(CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively
reduced CRF peptide levels in the basolateral amygdala of El mice. El mice
exhibited lower social investigation times than ddY counterparts, whereas central
administration of CRF-SAP normalized social investigation times relative to ddY
controls. Moreover, handling-induced seizures in El mice were reduced by 50%
following treatment with CRF-SAP relative to saporin alone-injected El controls.
The results of this study suggest that tonically activated CRF systems in the El
mouse brain suppress affiliative behavior and facilitate evoked seizures.
PMID- 17027342
TI - Removed: Integrative differential gene expression analysis for cross-platform
microarray datasets.
AB - This article has been removed, consistent with Elsevier Policy on Article
Withdrawal. Please see . The Publisher apologizes for any inconvenience this may
cause.
PMID- 17027343
TI - Evaluation of a brief cardiovascular autonomic screen.
AB - OBJECTIVE: To test the validity and practicality of a simple, rapid autonomic
cardiovascular evaluation (RACE). INTRODUCTION: Assessment of the autonomic
nervous system is costly and time consuming. Consequently, briefer measures are
often utilized as evaluations of autonomic function. We therefore set out to
assess the validity and practicality of a simple, rapid autonomic cardiovascular
evaluation protocol which mimicked the bedside evaluations used in many
healthcare centers. DESIGN/METHODS: Every eligible patient undergoing full
autonomic testing (FAT) in our laboratory was enrolled. The protocol, performed
blinded to FAT results, consisted of one breath in the supine position, and
supine and standing (1 and 3 min) pressures and pulse. Results were scored for
cardiac variation during the breath, a drop in pressure during the stand. Pulse
increase was also scored. Aggregate RACE score was regressed against a similarly
scored FAT. RESULTS: The single breath response correlated poorly with the
standard response to deep breathing with convergent results in only 26/37
patients, with a specificity of 30%, and sensitivity of 85%. HR and BP changes
standing showed little regression against matching values during FAT. Only 5/11
patients who met the criteria for postural tachycardia syndrome by FAT
demonstrated a >20 bpm increase in HR by 3 min standing. Finally, aggregate
scores for FAT and RACE correlated poorly. DISCUSSION: The RACE does not satisfy
the criteria to serve as a robust dysautonomia screen. Full autonomic testing
provides more complete and accurate information than simple bedside assessment.
PMID- 17027344
TI - Genetic heterogeneity among visceral and post-Kala-Azar dermal leishmaniasis
strains from eastern India.
AB - In India and Sudan, some patients of visceral leishmaniasis develop post-Kala
Azar dermal leishmaniasis (PKDL) while majority will not. Similarly, the clinical
manifestations and treatment outcome are reported to vary from district to
district and state to state in India. Present study is focused on to find out the
genetic variations between VL & PKDL causing strains. Nuclear DNA from 24 strains
of Leishmania donovani, isolated from patients of visceral leishmaniasis (18) and
PKDL (6) was extracted and digested with PstI restriction enzyme followed by
southern hybridization using Dig labeled beta-tubulin as probe. The results
showed three different banding patterns among 18 VL strains. However, all PKDL
isolates showed a genetic homogeneity within themselves but heterogeneity from VL
isolates. Interestingly maximum heterogenic groups were found in Bihar but all
isolates from West Bengal showed a single genotype origin. This study shows that
genetic mutations might be responsible for such variation and development of PKDL
in visceral strains of Indian L. donovani.
PMID- 17027345
TI - BRCA1 ubiquitylation of CtIP: Just the tIP of the iceberg?
AB - Ubiquitylation is an important regulatory mechanism of many cellular processes.
The breast and ovarian cancer-specific tumour suppressor BRCA1 is well
acknowledged to be a RING/E3 ubiquitin ligase, however, identification of its
physiological substrates has proved elusive. Recently published data have shown
that the BRCA1-interacting protein CtIP is in fact ubiquitylated by BRCA1, and
opens new avenues for the isolation of other substrate proteins.
PMID- 17027346
TI - A specific database for providing local and national level of integration of
clinical data in cystic fibrosis.
AB - It has recently been stated that a database is an essential tool in the
management of CF. The purpose of this work is to create a specific database
allowing optimal performance of storage, search and retrieval functions on
patients with CF. A specific database was developed using a Windev licence, for
application via Microsoft supported platforms or Intranet system. The database
allows real-time point of care data management of medical, investigational and
administrative data. It is currently being used in the 6 Belgian reference
centres. It represents a useful tool for gathering information on routine
clinical and lab data, bacteriology, treatments, complications and specific
outcomes for clinical and research purposes. The ongoing evolution of the
database includes enhancements toward research data orientation including
comparison of patient data between different centres and completeness of the
National CF registry questionnaire. A complimentary copy of the software can be
provided to multidisciplinary accredited CF centres worldwide upon request.
PMID- 17027347
TI - Long-term facilitation of breathing is absent after episodes of hypercapnic
hypoxia in awake humans.
AB - Despite the failure by many previous investigators to demonstrate a long-term
facilitation of breathing following episodes of hypoxia in awake humans, we
attempted to produce it using a pattern of hypercapnic hypoxic episodes similar
to that experienced by obstructive sleep apnoea patients, reasoning that if long
term facilitation was relevant to these patients then it is appropriate to test
the effectiveness of such episodes. Ten subjects drawn from the University
student population were instrumented to measure ventilation, heart rate and end
tidal PCO2 and PO2 breath-by-breath while seated in a comfortable reclining
chair. After an initial resting period breathing room air they experienced
fifteen, 30-s episodes breathing 6% O2 and 5% CO2 separated by 90 s of breathing
air. We examined the measured variables for an hour after the episodes but found
no trends toward an increase in ventilation or decrease in end-tidal PCO2 that
would indicate the presence of a long-term facilitation. We therefore concluded
that long-term facilitation of ventilation was not demonstrated in awake humans
using this pattern of stimuli.
PMID- 17027348
TI - Recurrent obstructive apneas trigger early systemic inflammation in a rat model
of sleep apnea.
AB - Obstructive sleep apnea (OSA) is associated with vascular disorders possibly due
to systemic inflammation. To determine whether repeated episodes of OSA in a rat
model lead to endothelial cell activation and systemic leukocyte recruitment in
the microcirculation. Three experimental groups (apnea, sham and naive) were
studied. The apnea group was instrumented and subjected to repeated obstruction
for 3h (rate 60/h, length 5s) using a special device. The sham group was only
instrumented and the naive group was used as a control. Leukocyte-endothelial
cell interactions (intravital microscopy) and expression of P-selectin
(immunohistochemistry) were determined in colonic venules. The apnea group
induced a significant increase in the flux of leukocytes rolling, number of
rolling leukocytes and number of adherent leukocytes when compared with the sham
or naive groups. P-selectin was up-regulated only in the apnea group. This
experimental model of recurrent obstruction demonstrates rapid endothelial cell
activation, suggesting the onset of an inflammatory response.
PMID- 17027349
TI - Simple liquid chromatography-tandem mass spectrometry method for determination of
novel anti-methicillin-resistant Staphylococcus aureus fluoroquinolone WCK 771 in
human serum.
AB - A simple, rapid, specific, precise, accurate and sensitive method for
determination of WCK 771 in human serum has been developed. The method uses high
performance liquid chromatography with tandem mass spectrometric detection.
Sample preparation involves protein precipitation method by addition of
acetonitrile. Gatifloxacin was used as internal standard. The response was found
to be linear from 0.312 to 40 microg/ml of serum with correlation coefficient
greater than 0.99. Limit of detection and lower limit of quantification for WCK
771 was found to be 0.078 microg/ml and 0.312 microg/ml, respectively. The intra
day precision and accuracy from analysis of quality control (QC) samples at four
concentrations was in the range of 2.36-2.58% and from 96.71 to 103.2%,
respectively. The inter-day precision and accuracy from analysis of quality
control samples at four concentrations was in the range of 3.14-6.82% and from
96.84 to 105.76%, respectively. WCK 771 was found to be stable for 24 h at auto
injector environment. WCK 771 was also found to be stable for 2h in serum at 25+/
3 degrees C and for 3 months at -20 degrees C. Mean absolute recovery at four
different concentrations was 86.92% with standard deviation of 1.79. Throughput
of the method is approximately one sample every 4 min. The method was also
reproduced with monkey serum. The method was employed for estimation of drug
serum levels during pre-clinical and clinical trials.
PMID- 17027350
TI - Optimal operation conditions for protein separation in hydrophobic interaction
chromatography.
AB - Protein retention in hydrophobic interaction chromatography is determined by
protein physicochemical properties and by system characteristics. In this paper
we present an attempt to determine the optimal operation conditions that would
allow the separation of binary protein mixtures. The statistically significant
system variables were determined, and then empirical models were obtained which
explained more than 92% of variability in dimensionless retention time based on
salt properties, ionic strength of the initial eluent and substitution degree of
the resin. These variables were optimized in order to achieve the maximum
retention time difference between two proteins in a mixture. The optimum
operation conditions as predicted by the models were tested experimentally,
showing a good agreement with predicted separation. We concluded that it would be
possible to determine the system conditions that allow the maximum separation of
two proteins based on the main system properties. The methodology proposed here
presents potential to be applied to partially characterized systems, however, it
could be improved if protein's properties were included explicitly in the models.
PMID- 17027351
TI - Comparison of the internal dynamics of globular proteins in the microcrystalline
and rehydrated lyophilized states.
AB - Natural abundance solid-state 13C-NMR spin-lattice relaxation experiments in the
laboratory (T1) and off-resonance rotating (T(1rho)) frames were applied for
qualitative comparison of the internal molecular dynamics of barstar, hen egg
white lysozyme and bacteriophage T4 lysozyme in both the microcrystalline and the
rehydrated (water content is 50% of the protein mass) lyophilized states. The
microcrystalline state of proteins provides a better spectral resolution;
however, less is known about the local structure and dynamics in the different
states. We found by visual comparison of both T1 and T(1rho) relaxation decays of
various resonance bands of the CPMAS spectra that within the ns-mus range of
correlation times there is no appreciable difference in the internal dynamics
between rehydrated lyophilized and crystalline states for all three proteins
tested. This suggests that the internal conformational dynamics depends weakly if
at all on inter-protein interactions in the solid state. Hence, physical
properties of globular proteins in a fully hydrated solid state seem to be
similar to those in solution. This result at least partly removes concerns about
biological relevance of studies of globular proteins in the solid state.
PMID- 17027353
TI - The second National Institutes of Health International Congress on advances in
uterine leiomyoma research: conference summary and future recommendations.
AB - OBJECTIVE: To summarize the proceedings of the Advances in Uterine Leiomyoma
Research: 2nd NIH International Congress, which was convened on February 24-25,
2005 by the Department of Health and Human Services (DHHS), National Institutes
of Health (NIH) in Bethesda, Maryland. DESIGN: Scientific information was
presented at a 2-day conference, which was a collaborative effort of agencies
across the DHHS and members of the academic, clinical, and medical communities
involved in uterine leiomyoma research. CONCLUSION(S): The conference brought
together scientists in biomedicine, epidemiology, basic research, therapeutics,
and translational medicine and fostered an exchange of scientific information
among members of the uterine leiomyoma research and health care communities. This
document summarizes this exchange and outlines research needs and recommendations
for future research directions.
PMID- 17027354
TI - Toward developing a once-a-month pill: a double-blind, randomized, controlled
trial of the effect of three single doses of mifepristone given at midcycle on
the pattern of menstrual bleeding.
AB - OBJECTIVE: To test the feasibility of timing the administration of mifepristone
as a once-a-month contraceptive pill on the 12th day before the next menses, as
calculated from the length of the previous menstrual cycles. DESIGN: Double
blind, randomized, controlled trial. SETTING: Five family planning centers across
the world. PATIENT(S): Three hundred ninety-nine women attending family planning
clinics. INTERVENTION(S): Randomized to receive 10, 25, or 200 mg of mifepristone
or a placebo. MAIN OUTCOME MEASURE(S): Lengthening or shortening of the normal
menstrual cycle length following administration of the drug by at least 5 days.
RESULT(S): The menstrual period came within 5 days of the predicted date in 88%
of women receiving the placebo, 84% of women receiving 10 mg, 72% of women
receiving 25 mg of mifepristone, and only 48% of women treated with 200 mg of
mifepristone. Increasing the dose of mifepristone was associated with an
increased chance of having a delayed period (P<.001). Only 45% of women were in
the peri-ovulatory phase of the cycle according to LH and P measurements on the
day of drug administration. Women treated before ovulation were more likely to
have delayed menses with all three doses of mifepristone. CONCLUSION(S): Because
of the disruption in cycle length, it appears unlikely that mifepristone
administered once a month, at a calendar-based time, would provide a reliable
method of contraception.
PMID- 17027355
TI - Prediction of embryo developmental potential and pregnancy based on early stage
morphological characteristics.
AB - OBJECTIVE: To analyze the association between morphological details at different
stages of culture with blastocyst development, with an aim to improve selection
for transfer. DESIGN: Retrospective audit of data. SETTING: Tertiary referral
center and university hospital. PATIENT(S): Two hundred sixty-eight couples
underwent 357 treatment cycles. INTERVENTION(S): Oocyte pickups for IVF or
intracytoplasmic sperm injection (ICSI) after ovarian stimulation. Embryos were
individually cultured and examined on days 0-2 for morphological details and
developmental characteristics, and selected for transfer, freezing, or further
culture. MAIN OUTCOME MEASURES: The association of blastocyst development and
pregnancy with morphological characteristics. RESULT(S): Five morphological
characteristics (appearance of the cytoplasm, pronuclei and nucleoli, cytoplasmic
deficit, and developmental rate) showed the strongest association with blastocyst
development. By combining information from all days of culture into a cumulative
score, prediction was greatly improved, compared to only using day 2 morphology.
Cytoplasmic dysmorphisms of the oocyte, including accumulation of smooth
endoplasmic reticulum, were associated with poor developmental performance.
Differential weighting of these characteristics was included in a new embryo
scoring system, which showed a strong correlation with implantation.
CONCLUSION(S): Weighting individual morphological characteristics of zygotes and
embryos and combining them into a cumulative embryo score can improve selection
of embryos for transfer.
PMID- 17027356
TI - Association between androgen receptor gene CAG trinucleotide repeat length and
testicular histology in older men.
AB - OBJECTIVE: To determine whether the size of CAG repeat in exon 1 of the androgen
receptor (AR) gene is related to impaired spermatogenesis in older men. DESIGN:
Study of two groups of older men: one with preserved spermatogenesis and the
other with arrested spermatogenesis. SETTING: University teaching hospital.
PATIENT(S): Twenty-eight men aged from 53 to 102 years. INTERVENTION(S): The DNA
fragment encoding the AR polyglutamine tract was amplified from DNA of testis
tissue. MAIN OUTCOME MEASURE(S): The size of the CAG repeat was evaluated by
using fluorescent-labeled polymerase chain reaction performed on an ABI Prism 377
DNA sequencer followed by automated analysis with Genscan 3.1.2 software.
RESULT(S): Mean CAG repeat length was 22.76 +/- 3 in the group of 13 aged men
with preserved spermatogenesis and 21.86 +/- 2.23 in the group of 15 aged men
with arrested spermatogenesis. CONCLUSION(S): Impaired spermatogenesis in elderly
men does not seem to be correlated with the AR gene CAG repeat length, which
therefore does not appear to be a risk factor for impaired spermatogenesis in
older men.
PMID- 17027357
TI - Reactive oxygen species as an independent marker of male factor infertility.
AB - OBJECTIVE: To determine the abnormal patterns of reactive oxygen species (ROS)
production in male factor infertility (MFI) patients and to define the ROS
reference values in such patients. DESIGN: A retrospective study. SETTING: Male
infertility clinic at a tertiary healthcare center. PATIENT(S): We examined 132
MFI patients (all normal sperm parameters, n = 24, and all abnormal sperm
parameters, n = 38) and 34 healthy donors. INTERVENTION(S): Routine semen
analysis, measurement of ROS. MAIN OUTCOME MEASURE(S): Sperm parameters, ROS
levels (10(4) cpm/20 x 10(6) sperm). RESULT(S): Normal, healthy donors had
significantly higher (P<.0001) sperm concentration, motility, and morphology
compared with all MFI patients. Univariate analysis indicated a significant
association between MFI and log (ROS + 1) (odds ratio [OR] = 3.84), besides sperm
parameters and age. A multivariate model using logistic regression analysis also
indicated an independent association of log ROS with MFI (OR = 4.25). The ROS
cutoff values of 1.2-1.4 had a sensitivity of 0.70-0.78 with a corresponding
specificity of 0.82. However, at a cutoff point of 1.2, the OR was 68.6, which
increased with an increase in the cutoff. CONCLUSION(S): High ROS is an
independent marker of MFI, irrespective of whether these patients have normal or
abnormal semen parameters. We suggest the inclusion of ROS measurement as part of
idiopathic infertility evaluation. Treatment with antioxidants may be beneficial
in such patients.
PMID- 17027358
TI - Pubertal evaluation of adolescent boys with beta-thalassemia major and delayed
puberty.
AB - OBJECTIVE: To examine the hormonal status of the hypothalamic-pituitary-gonadal
axis in adolescent males with beta-thalassemia major. DESIGN: Controlled clinical
study. SETTING: Tertiary referral teaching hospital. PATIENT(S): Thirty-three
adolescent males with beta-thalassemia major. INTERVENTION(S): Basal LH, FSH, and
T were examined. All individuals received 100 microg GnRH analogue. Four hours
later the hormone levels were retested. Patients with beta-thalassemia and low T
levels received hCG. MAIN OUTCOME MEASURE(S): The preintervention and
postintervention levels of FSH, LH, and T were examined. RESULT(S): Of the 33
beta-thalassemia major adolescents, 17 had delayed puberty. The difference in
basal LH, FSH, and T levels between delayed and normal puberty beta-thalassemia
groups were statistically significant. These levels were significantly lower
compared with the constitutional delayed puberty group and become even more
significant after GnRH analogue administration. The T levels in the beta
thalassemia group were significantly lower than in the control group. After hCG
administration, the T levels remained significantly lower in the delayed-puberty
beta-thalassemia compared to the normal-puberty beta-thalassemia group.
CONCLUSION(S): Despite recent therapeutic advances in the management of beta
thalassemia major, the risk of secondary endocrine dysfunction remains high.
Hypogonadism is one of the most frequent endocrine complications.
PMID- 17027359
TI - Interleukin-18 system messenger RNA and protein expression in human endometrium
during the menstrual cycle.
AB - OBJECTIVE: To investigate the IL-18 system, including IL-18, IL-18 receptor (IL
18R), IL-18 binding protein (IL-18BP), and IL-18 precursor (proIL-18), mRNA and
protein expression in human endometrium during the menstrual cycle. DESIGN:
Controlled study. SETTING: Clinical and academic research setting in a university
medical center. PATIENT(S): Human endometrium was obtained from surgical
specimens of normal cycling women undergoing hysterectomy for benign reasons.
INTERVENTION(S): A total of 24 human endometrium samples were obtained at
proliferative and secretory phase from surgical specimens of normal cycling women
undergoing hysterectomy. Quantitative competitive polymerase chain reaction (QC
PCR) and immunohistochemistry were performed. MAIN OUTCOME MEASURE(S): The
differences of IL-18 system mRNA and the ratio of antagonist to agonist in both
proliferative and secretory phases of endometrium were analyzed. RESULT(S): Our
results showed a complete IL-18 system, including mRNA expression and protein
production in both proliferative and secretory phases of the endometrium. The QC
PCR demonstrated that both IL-18 and IL-18R decreased and IL-18BP increased mRNA
expression in human endometrium in secretory phase compared with proliferative
phase. A positive correlation of IL-18 and IL-18R in human endometrium was
demonstrated in proliferative phase but not in secretory phase. In addition,
there is a significantly higher ratio of IL-18BP to IL-18 mRNA levels in
secretory endometrium compared with proliferative phase endometrium (P<.05).
CONCLUSION(S): The expression and ratio of IL-18 antagonist to agonist may be
responsible for embryo implantation.
PMID- 17027360
TI - Serum sex hormone-binding globulin levels show too much variability to be used
effectively as a screening marker for insulin resistance in women with polycystic
ovary syndrome.
AB - OBJECTIVE: To evaluate the relationship between serum sex hormone-binding
globulin (SHBG) and parameters of insulin sensitivity in women with polycystic
ovary syndrome (PCOS) and controls, and determine the feasibility of using SHBG
levels to predict insulin resistance. DESIGN: Evaluation of a prospectively
collected database. SETTING: University reproductive center. PATIENT(S): A total
of 21 women with PCOS and 17 controls. INTERVENTION(S): Oral glucose tolerance
test. MAIN OUTCOME MEASURE(S): Correlations of serum SHBG and parameters of
insulin sensitivity. RESULT(S): [1] Among all participants, SHBG levels indicated
a correlation between the fasting glucose-to-insulin (GI) ratio and the
quantitative insulin sensitivity check index (QUICKI). Participants with PCOS
demonstrated significant correlations of SHBG and fasting GI ratio, 1-hour
postglucola insulin levels, and random 17-hydroxyprogesterone (17ohP4) levels.
Among controls, SHBG and fasting serum glucose and 2-hour postglucola serum
glucose levels were associated. [2] Participants with PCOS and lean controls
exhibited different glucose and insulin responses to 75 g of glucose at 1 and 2
hours postchallenge, resulting in paradoxically similar GI ratios. CONCLUSION(S):
[1] Although certain parameters of insulin status and serum SHBG demonstrated
statistically significant correlation coefficients, these relationships are weak
and SHBG cannot be used as a predictor of insulin resistance. [2] The post
glucose load GI ratio cannot be used to determine the magnitude of insulin
resistance.
PMID- 17027361
TI - Preimplantation genetic diagnosis of Marfan syndrome using multiple displacement
amplification.
AB - OBJECTIVE: To evaluate the use of multiple displacement amplification (MDA) for
whole-genome amplification in the preimplantation genetic diagnosis (PGD) of
Marfan syndrome. DESIGN: Multiple displacement amplification was used to amplify
the whole-genome directly from a single cell. The MDA product was used for
polymerase chain reaction (PCR) analysis of five different loci. At this point
MDA was used to develop a PGD-Marfan syndrome program. SETTING: Fertility and
gynecology private center in Alicante, Spain. PATIENT(S): A couple in which the
husband is affected by Marfan syndrome and carries a novel mutation in the FBN-1
gene. INTERVENTION(S): The MDA of single cells and PCR tests for PGD. MAIN
OUTCOME MEASURE(S): Allele drop-out (ADO), amplification efficiency rates, and
the ability to detect Marfan syndrome using MDA. RESULT(S): We report that
isothermal whole-genome amplification from single cells allowed analysis of five
different loci using standard conditions. The development of a MDA-PGD protocol
for Marfan syndrome allowed for the diagnosis of seven embryos. These were
biopsied on day 3 of culture and analyzed. Two healthy embryos were transferred
48 hours after culture, resulting in a singleton ongoing pregnancy and the birth
of a healthy child. CONCLUSION(S): The MDA technique is useful for overcoming the
problem of insufficient genomic DNA in PGD. The use of MDA as a universal step
marks a new cycle for PGD as it allows for the diagnosis of any known gene defect
by standard methods and conditions.
PMID- 17027363
TI - Presence of hydrosalpinx correlated to endometrial inflammatory response in vivo.
AB - OBJECTIVE: To evaluate and compare the inflammatory response and mediators in the
endometrium of patients with hydrosalpinges compared with normal controls.
DESIGN: Retrospective case-control study. SETTING: Urban medical center.
PATIENT(S) AND INTERVENTION(S): Hysterectomy samples were identified as being
affected by hydrosalpinx or salpingitis (n = 30) and were age-matched with
control samples (n = 30). INTERVENTIONS: Fallopian tube and endometrial slides
were analyzed for leukocytes and immunohistochemical techniques performed for
cytokines (interleukin-2 [IL-2]). MAIN OUTCOME MEASURE(S): Evaluate and compare
the endometrial inflammatory response (leukocytes and cytokines) from samples
affected and non-affected by hydrosalpinx and salpingitis. RESULT(S): Examination
of tubal and endometrial slides with hydrosalpinx demonstrated a statistically
significant increase in the number of overall inflammatory cells. High-intensity
immunohistochemical staining for IL-2 was demonstrated in 7.4% of controls versus
65% of cases. CONCLUSION(S): A defined, identifiable, local response to
hydrosalpingeal fluid has been demonstrated in the endometrium. This response
consists of statistically significant elevations of leukocytes and IL-2. An
inflammatory endometrial response may be an independent contributor to the
decreased reproductive outcome observed in patients with hydrosalpinges.
PMID- 17027362
TI - A randomized prospective study of misoprostol or mifepristone followed by
misoprostol when needed for the treatment of women with early pregnancy failure.
AB - OBJECTIVE: To compare the effectiveness and safety of misoprostol and
mifepristone, followed when needed by misoprostol, for the treatment of women
with early pregnancy failure. DESIGN: Prospective randomized nonblinded
controlled trial. SETTING: University-affiliated tertiary medical center.
PATIENT(S): One hundred fifteen consecutive women diagnosed as having a blighted
ovum or missed abortion of <9 weeks of gestation enrolled. INTERVENTION(S): The
patients received orally 600 mg mifepristone (group I) or orally 800 microg
misoprostol (group II). Most patients in both groups subsequently received 48
hours later orally 800 microg misoprostol. MAIN OUTCOME MEASURE(S): Failure was
defined as surgical intervention due to retained gestational sac 48 hours after
completion of the drug protocol, severe symptoms, or suspected retained products
of conception after the menstrual period. RESULT(S): The success rate was similar
in groups I and II: 38 of 58 patients (65.5%) versus 42 of 57 patients (73.6%),
respectively. No cases of severe infection or bleeding necessitating blood
transfusion occurred. CONCLUSION(S): Misoprostol is an effective and safe
treatment for early pregnancy failure and could replace surgical curettage in
over two-thirds of the patients. Mifepristone offers no advantage compared with
misoprostol as initial treatment.
PMID- 17027364
TI - Early postoperative changes in testosterone, dehydroepiandrosterone sulfate, and
sex hormone-binding globulin after hysterectomy with or without concomitant
oophorectomy.
AB - OBJECTIVE: To investigate the cross-sectional associations of hysterectomy and
oophorectomy status, chronological age, and body mass index with early
postoperative plasma levels of total and free T, DHEAS, and sex hormone-binding
globulin (SHBG). DESIGN: A cross-sectional study. SETTING: University hospital.
PATIENT(S): Ninety-two women age 35-47 years who were scheduled for hysterectomy
and/or oophorectomy, advocated for benign gynecological pathologies.
INTERVENTION(S): Ninety-two eligible premenopausal women underwent hysterectomy
and/or oophorectomy, with plasma T, DHEAS, and SHBG levels assayed before surgery
and during the postoperative period. MAIN OUTCOME MEASURE(S): Effects of time x
operation and age x operation interactions between oophorectomized and
nonoophorectomized groups and within-subject main effect of time on plasma
androgen levels. RESULT(S): Of 92 women, hysterectomy alone was performed in only
49 (53.3%) cases. Oophorectomy, either unilateral or bilateral, was performed in
35.8% of cases. Age x within-group interactions exhibited an important difference
(P=.03) in total T levels. The time x between- and within-group interaction
effects on plasma DHEAS levels of postoperative day 7, compared with day 1, were
statistically significant (P<.001). The effect of time x group interaction was
remarkable, in terms of SHBG levels during the postoperative period. Age x
oophorectomy interaction exhibited a statistically significant change of decline
in DHEAS levels on postoperative day 7 (P=.05). CONCLUSION(S): The present study
demonstrated a time and operation effect decline in plasma DHEAS levels. In
contrast, the time x operation interaction on SHBG levels exhibited an increase
toward postoperative day 7.
PMID- 17027366
TI - Ectopic nucleolus organizer regions in a patient with premature ovarian failure.
AB - OBJECTIVE: To present a case of premature ovarian failure (POF) and a complex
chromosomal rearrangement involving band Xq21. DESIGN: Case report. SETTING:
Department of cytogenetics, general analysis laboratory. PATIENT(S): A woman with
POF and a complex translocation involving chromosomes X and 2 and a nucleolus
organizer region (NOR) structure inserted in the critical region Xq21.
INTERVENTION(S): Chromosomal analysis, NOR banding, hysteroscopy. MAIN OUTCOME
MEASURE(S): Fluorescence in situ hybridization, comparative genome hybridization,
human androgen receptor gene technique. RESULT(S): Four mechanisms may explain a
causal relationship between the phenotype of the patient and her chromosome
constitution. The presence of a NOR structure at the breakpoint of chromosome X
suggests a complex reorganization and is of interest per se. CONCLUSION(S):
Cytogenetic analysis is essential in women with unexplained POF and may provide
valuable information on the chromosome location of critical regions implicated in
ovarian function. However, in very complex reorganizations such as that described
herein, classical cytogenetic techniques must be combined with molecular
techniques to achieve a more complete characterization of the anomaly.
PMID- 17027365
TI - Whole-arm translocations between chromosome 1 and acrocentric G chromosomes are
associated with a poor prognosis for spermatogenesis: two new cases and review of
the literature.
AB - OBJECTIVE: To analyze unusual translocations involving a chromosome 1 whole arm
and an acrocentric G chromosome p arm found in two men with azoospermia. DESIGN:
Case report with review of the scientific literature. SETTING: Cytogenetics
department. PATIENT(S): Two men with azoospermia and normal hormonal levels.
INTERVENTIONS(S): Peripheral blood lymphocytes were obtained for karyotype, and
metaphases were studied by standard GBG, RBG, and CBG banding procedures. MAIN
OUTCOME MEASURE(S): Karyotype GBG, RBG, and CBG banding. RESULT(S): Karyotype
revealed balanced translocation involving a chromosome 1 whole arm and an
acrocentric G chromosome p arm: 46,XY,t(1;21)(q11;p13) (patient 1) and
46,XY,t(1;22)(q11;p11) (patient 2). CONCLUSION(S): With regard to published cases
of whole-arm translocation of human chromosome 1 with an acrocentric p arm and a
maternal origin of these abnormalities, we argue for an impairment of meiosis
resulting in a high probability of quadrivalent-XY-body interaction. Male factor
infertility might be due to two poor prognostic factors, first the involvement of
human chromosome 1 (and its heterochromatic region) and second the involvement of
an acrocentric chromosome p-arm breakpoint. This probable interaction between the
pachytene quadrivalent and XY body might explain azoospermia.
PMID- 17027367
TI - Symptoms of premenstrual syndrome may be caused by hyperventilation.
AB - OBJECTIVE: To determine whether women with premenstrual syndrome (PMS) differ
from healthy women in the extent of hyperventilation during the luteal phase of
the cycle. DESIGN: Case report. SETTING: Medical university. PATIENT(S): Three
reproductive-age women with severe symptoms of PMS in whom dramatic decline in
end-tidal PCO2 (PETCO2) occurred during the luteal phase of the cycle.
INTERVENTION(S): Measurements of PETCO2, administration of GnRH agonist
triptorelin. MAIN OUTCOME MEASURE(S): PETCO2 was determined daily by sidestream
capnometry. RESULT(S): The decline in PETCO2 in women with PMS was 12-18 mm Hg,
on the average. This was significantly more pronounced than the decline of PETCO2
that was observed in healthy women. With the decline of PETCO2 the symptoms of
PMS appeared. Symptoms disappeared at the end of the luteal phase when PETCO2 was
increasing again. During treatment with the GnRH agonist, PETCO2 did not decline,
and all women were free of symptoms. CONCLUSION(S): The symptoms of PMS observed
in our patients were associated with a pronounced decline of PETCO2 that occurred
during the luteal phase of the cycle. Because the symptoms were similar to
symptoms observed in the chronic hyperventilation syndrome it is suggested that
some symptoms of PMS may be caused by chronic hyperventilation. It appears that
in women with PMS the sensitivity of the respiratory center to CO2 is increased
more than normal by P or some other secretory product of the corpus luteum,
resulting in pronounced hyperventilation with the associated clinical signs and
symptoms of a chronic hyperventilation syndrome.
PMID- 17027368
TI - Infertility in a man with oligoasthenoteratozoospermia associated with
nonrobertsonian translocation t(9;15)(p10;q10).
AB - OBJECTIVE: To analyze an unusual nonrobertsonian translocation t(9;15)(p10;q10)
found in an infertile man with oligoasthenoteratozoospermia who had a normal
phenotype. DESIGN: Case report with a review of scientific literature. SETTING:
Academic research environment. PATIENT(S): Infertile man with
oligoasthenoteratozoospermia but otherwise apparently healthy. INTERVENTION(S):
Peripheral blood lymphocytes were obtained for karyotyping, and metaphases were
studied by the GBG fluorescence in situ hybridization (FISH) procedure. MAIN
OUTCOME MEASURE(S): Physical examination, semen analysis, GBG banding, and FISH
procedure. RESULT(S): The semen analysis revealed oligoasthenoteratozoospermia.
The lymphocytic karyotype detected a translocation t(9;15)(p10;q10), and FISH
procedure showed that the derived chromosome had a chromosome 15 centromere.
CONCLUSION(S): The association of unusual translocation with male factor
infertility was described. To our knowledge no such association has been
described previously in men whose clinical manifestation is only infertility.
PMID- 17027369
TI - Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian
failure.
AB - Mutational screening of the bone morphogenetic protein 15 (BMP15) and growth
differentiation factor 9 (GDF9) genes in a population with premature ovarian
failure (POF) identified no new mutations. However, three single nucleotide
polymorphisms in the BMP15 gene, two in the 5' untranslated region (31T>G and
71C>G) and another in exon 1 (387G>A), were found to be common in both POF and
control groups.
PMID- 17027370
TI - Oxygen, cyanide and energy generation in the cystic fibrosis pathogen Pseudomonas
aeruginosa.
AB - Pseudomonas aeruginosa is a gram-negative, rod-shaped bacterium that belongs to
the gamma-proteobacteria. This clinically challenging, opportunistic pathogen
occupies a wide range of niches from an almost ubiquitous environmental presence
to causing infections in a wide range of animals and plants. P. aeruginosa is the
single most important pathogen of the cystic fibrosis (CF) lung. It causes
serious chronic infections following its colonisation of the dehydrated mucus of
the CF lung, leading to it being the most important cause of morbidity and
mortality in CF sufferers. The recent finding that steep O2 gradients exist
across the mucus of the CF-lung indicates that P. aeruginosa will have to show
metabolic adaptability to modify its energy metabolism as it moves from a high O2
to low O2 and on to anaerobic environments within the CF lung. Therefore, the
starting point of this review is that an understanding of the diverse modes of
energy metabolism available to P. aeruginosa and their regulation is important to
understanding both its fundamental physiology and the factors significant in its
pathogenicity. The main aim of this review is to appraise the current state of
knowledge of the energy generating pathways of P. aeruginosa. We first look at
the organisation of the aerobic respiratory chains of P. aeruginosa, focusing on
the multiple primary dehydrogenases and terminal oxidases that make up the highly
branched pathways. Next, we will discuss the denitrification pathways used during
anaerobic respiration as well as considering the ability of P. aeruginosa to
carry out aerobic denitrification. Attention is then directed to the limited
fermentative capacity of P. aeruginosa with discussion of the arginine deiminase
pathway and the role of pyruvate fermentation. In the final part of the review,
we consider other aspects of the biology of P. aeruginosa that are linked to
energy metabolism or affected by oxygen availability. These include cyanide
synthesis, which is oxygen-regulated and can affect the operation of aerobic
respiratory pathways, and alginate production leading to a mucoid phenotype,
which is regulated by oxygen and energy availability, as well as having a role in
the protection of P. aeruginosa against reactive oxygen species. Finally, we
consider a possible link between cyanide synthesis and the mucoid switch that
operates in P. aeruginosa during chronic CF lung infection.
PMID- 17027371
TI - Structure, mechanism and physiological roles of bacterial cytochrome c
peroxidases.
AB - Cytochrome-c peroxidases (CCPs) are a widespread family of enzymes that catalyse
the conversion of hydrogen peroxide (H2O2) to water using haem co-factors. CCPs
are found in both eukaryotes and prokaryotes, but the enzymes in each group use a
distinct mechanism for catalysis. Eukaryotic CCPs contain a single b-type haem co
factor. Conventional bacterial CCPs (bCCPs) are periplasmic enzymes that contain
two covalently bound c-type haems. However, we have identified a sub-group of
bCCPs by phylogenetic analysis that contains three haem-binding motifs. Although
the structure and mechanism of several bacterial di-haem CCPs has been studied in
detail and is well understood, the physiological role of these enzymes is often
much less clear, especially in comparison to other peroxidatic enzymes such as
catalase and alkyl-hydroperoxide reductase. In this review, the structure,
mechanism and possible roles of bCCPs are examined in the context of their
periplasmic location, the regulation of their synthesis by oxygen and their
particular function in pathogens.
PMID- 17027372
TI - Respiratory transformation of nitrous oxide (N2O) to dinitrogen by Bacteria and
Archaea.
AB - N2O is a potent greenhouse gas and stratospheric reactant that has been steadily
on the rise since the beginning of industrialization. It is an obligatory
inorganic metabolite of denitrifying bacteria, and some production of N2O is also
found in nitrifying and methanotrophic bacteria. We focus this review on the
respiratory aspect of N2O transformation catalysed by the multicopper enzyme
nitrous oxide reductase (N2OR) that provides the bacterial cell with an electron
sink for anaerobic growth. Two types of Cu centres discovered in N2OR were both
novel structures among the Cu proteins: the mixed-valent dinuclear Cu(A) species
at the electron entry site of the enzyme, and the tetranuclear Cu(Z) centre as
the first catalytically active Cu-sulfur complex known. Several accessory
proteins function as Cu chaperone and ABC transporter systems for the biogenesis
of the catalytic centre. We describe here the paradigm of Z-type N2OR, whose
characteristics have been studied in most detail in the genera Pseudomonas and
Paracoccus. Sequenced bacterial genomes now provide an invaluable additional
source of information. New strains harbouring nos genes and capability of N2O
utilization are being uncovered. This reveals previously unknown relationships
and allows pattern recognition and predictions. The core nos genes, nosZDFYL,
share a common phylogeny. Most principal taxonomic lineages follow the same
biochemical and genetic pattern and share the Z-type enzyme. A modified N2OR is
found in Wolinella succinogenes, and circumstantial evidence also indicates for
certain Archaea another type of N2OR. The current picture supports the view of
evolution of N2O respiration prior to the separation of the domains Bacteria and
Archaea. Lateral nos gene transfer from an epsilon-proteobacterium as donor is
suggested for Magnetospirillum magnetotacticum and Dechloromonas aromatica. In a
few cases, nos gene clusters are plasmid borne. Inorganic N2O metabolism is
associated with a diversity of physiological traits and biochemically challenging
metabolic modes or habitats, including halorespiration, diazotrophy, symbiosis,
pathogenicity, psychrophily, thermophily, extreme halophily and the marine
habitat down to the greatest depth. Components for N2O respiration cover
topologically the periplasm and the inner and outer membranes. The Sec and Tat
translocons share the task of exporting Nos components to their functional sites.
Electron donation to N2OR follows pathways with modifications depending on the
host organism. A short chronology of the field is also presented.
PMID- 17027373
TI - A circadian timing mechanism in the cyanobacteria.
AB - Cyanobacteria such as Synechococcus elongatus PCC 7942, Thermosynechococcus
elongatus BP-1, and Synechocystis species strain PCC 6803 have an endogenous
timing mechanism that can generate and maintain a 24 h (circadian) periodicity to
global (whole genome) gene expression patterns. This rhythmicity extends to many
other physiological functions, including chromosome compaction. These rhythmic
patterns seem to reflect the periodicity of availability of the primary energy
source for these photoautotrophic organisms, the Sun. Presumably, eons of
environmentally derived rhythmicity--light/dark cycles--have simply been
mechanistically incorporated into the regulatory networks of these cyanobacteria.
Genetic and biochemical experimentation over the last 15 years has identified
many key components of the primary timing mechanism that generates rhythmicity,
the input pathways that synchronize endogenous rhythms to exogenous rhythms, and
the output pathways that transduce temporal information from the timekeeper to
the regulators of gene expression and function. Amazingly, the primary timing
mechanism has evidently been extracted from S. elongatus PCC 7942 and can also
keep time in vitro. Mixing the circadian clock proteins KaiA, KaiB, and KaiC from
S. elongatus PCC 7942 in vitro and adding ATP results in a circadian rhythm in
the KaiC protein phosphorylation state. Nonetheless, many questions still loom
regarding how this circadian clock mechanism works, how it communicates with the
environment and how it regulates temporal patterns of gene expression. Many
details regarding structure and function of the individual clock-related proteins
are provided here as a basis to discuss these questions. A strong, data-intensive
foundation has been developed to support the working model for the cyanobacterial
circadian regulatory system. The eventual addition to that model of the metabolic
parameters participating in the command and control of this circadian global
regulatory system will ultimately allow a fascinating look into whole-cell
physiology and metabolism and the consequential organization of global gene
expression patterns.
PMID- 17027376
TI - Top-down facilitation of visual object recognition: object-based and context
based contributions.
AB - The neural mechanisms subserving visual recognition are traditionally described
in terms of bottom-up analysis, whereby increasingly complex aspects of the
visual input are processed along a hierarchical progression of cortical regions.
However, the importance of top-down facilitation in successful recognition has
been emphasized in recent models and research findings. Here we consider evidence
for top-down facilitation of recognition that is triggered by early information
about an object, as well as by contextual associations between an object and
other objects with which it typically appears. The object-based mechanism is
proposed to trigger top-down facilitation of visual recognition rapidly, using a
partially analyzed version of the input image (i.e., a blurred image) that is
projected from early visual areas directly to the prefrontal cortex (PFC). This
coarse representation activates in the PFC information that is back-projected as
"initial guesses" to the temporal cortex where it presensitizes the most likely
interpretations of the input object. In addition to this object-based
facilitation, a context-based mechanism is proposed to trigger top-down
facilitation through contextual associations between objects in scenes. These
contextual associations activate predictive information about which objects are
likely to appear together, and can influence the "initial guesses" about an
object's identity. We have shown that contextual associations are analyzed by a
network that includes the parahippocampal cortex and the retrosplenial complex.
The integrated proposal described here is that object- and context-based top-down
influences operate together, promoting efficient recognition by framing early
information about an object within the constraints provided by a lifetime of
experience with contextual associations.
PMID- 17027377
TI - Building the gist of a scene: the role of global image features in recognition.
AB - Humans can recognize the gist of a novel image in a single glance, independent of
its complexity. How is this remarkable feat accomplished? On the basis of
behavioral and computational evidence, this paper describes a formal approach to
the representation and the mechanism of scene gist understanding, based on scene
centered, rather than object-centered primitives. We show that the structure of a
scene image can be estimated by the mean of global image features, providing a
statistical summary of the spatial layout properties (Spatial Envelope
representation) of the scene. Global features are based on configurations of
spatial scales and are estimated without invoking segmentation or grouping
operations. The scene-centered approach is not an alternative to local image
analysis but would serve as a feed-forward and parallel pathway of visual
processing, able to quickly constrain local feature analysis and enhance object
recognition in cluttered natural scenes.
PMID- 17027378
TI - Beyond the face: exploring rapid influences of context on face processing.
AB - Humans optimize behavior by deriving context-based expectations. Contextual data
that are important for survival are extracted rapidly, using coarse information,
adaptive decision strategies, and dedicated neural infrastructure. In the field
of object perception, the influence of a surrounding context has been a major
research theme, and it has generated a large literature. That visual context, as
typically provided by natural scenes, facilitates object recognition as has been
convincingly demonstrated (Bar, M. (2004) Nat. Rev. Neurosci., 5: 617-629). Just
like objects, faces are generally encountered as part of a natural scene. Thus
far, the facial expression literature has neglected such context and treats
facial expressions as if they stand on their own. This constitutes a major gap in
our knowledge. Facial expressions tend to appear in a context of head and body
orientations, body movements, posture changes, and other object-related actions
with a similar or at least a closely related meaning. For instance, one would
expect a frightened face when confronted to an external danger to be at least
accompanied by withdrawal movements of head and shoulders. Furthermore, some cues
provided by the environment or the context in which a facial expression appears
may have a direct relation with the emotion displayed by the face. The brain may
even fill in the natural scene context typically associated with the facial
expression. Recognition of the facial expression may also profit from processing
the vocal emotion as well as the emotional body language that normally accompany
it. Here we review the emerging evidence on how the immediate visual and auditory
contexts influence the recognition of facial expressions.
PMID- 17027379
TI - The effectiveness of disruptive coloration as a concealment strategy.
AB - Our understanding of camouflage has been developing for over 100 years. Several
underlying principles have emerged. Background pattern matching, or crypsis, is
insufficient to conceal objects because of edge information. Other strategies
exist to disrupt the continuity of extended edges. These strategies are reviewed.
We pay particular attention to the theory of disruptive coloration, which
predicts that high-contrast elements located at the object edge will mask the
perception of a target as belonging to a certain category of object, in spite of
the fact that the edge elements are independently visible. Although this strategy
has long been assumed to be effective, there has been a lack of supportive data
involving the perception of targets by nonhuman animals. We present evidence,
from a field study, in support of the notion that disruptive coloration reduces
the chances of bird predation of artificial "moths."
PMID- 17027381
TI - From perceptive fields to Gestalt.
AB - Studies on visual psychophysics and perception conducted in the Freiburg
psychophysics laboratory during the last 35 years are reviewed. Many of these
were inspired by single-cell neurophysiology in cat and monkey. The aim was to
correlate perceptual phenomena and their effects to possible neuronal mechanisms
from retina to visual cortex and beyond. Topics discussed include perceptive
field organization, figure-ground segregation and grouping, fading and filling
in, and long-range color interaction. While some of these studies succeeded in
linking perception to neuronal response patterns, others require further
investigation. The task of probing the human brain with perceptual phenomena
continues to be a challenge for the future.
PMID- 17027382
TI - In honour of Lothar Spillmann - filling-in, wiggly lines, adaptation, and
aftereffects.
AB - I have studied a number of visual phenomena that Lothar Spillmann has already
elucidated. These include: Neon spreading: when a small red cross is superimposed
on intersecting black lines, the red cross seems to spread out into an illusory
disk. Unlike the Hermann grid, neon spreading is relatively unaffected when the
black lines are curved or wiggly. This suggests that the Hermann grid, but not
neon spreading, involves long-range interactions. Neon spreading can be shown in
random-dot patterns, even without intersections. It is strongest when the red
crosses are equiluminous with the gray background. Adaptation, aftereffects, and
filling-in: direct and induced aftereffects of color, motion, and dimming.
Artificial scotomata and filling-in: the "dam" theory is false. Staring at wiggly
lines or irregularly scattered dots makes them gradually appear straighter, or
more regularly spaced. I present evidence that irregularity is actually a visual
dimension to which the visual system can adapt. Conjectures on the nature of
peripheral fading and of motion-induced blindness. Some failed experiments on
correlated visual inputs and cortical plasticity.
PMID- 17027383
TI - Lightness, filling-in, and the fundamental role of context in visual perception.
AB - Visual perception is defined by the unique spatial interactions that distinguish
it from the point-to-point precision of a photometer. Over several decades,
Lothar Spillmann has made key observations about the nature of these interactions
and the role of context in perception. Our lab has explored the perceptual
properties of spatial interactions and more generally the importance of visual
context for neuronal responses and perception. Our investigations into the
spatiotemporal dynamics of lightness provide insight into underlying mechanisms.
For example, backward masking and luminance modulation experiments suggest that
the representation of a uniformly luminous object develops first at the borders
and, in some manner, the center fills in. The temporal dynamics of lightness
induction are also consistent with a filling-in process. There is a slow cutoff
temporal frequency above which surround luminance modulation will not elicit
perceptual induction of a central area. The larger the central area, the lower
the cutoff frequency for induction, perhaps indicating that an edge-based process
requires more time to "complete" the larger area. In recordings from primary
visual cortex we find that neurons respond in a manner surprisingly consistent
with lightness perception and the spatial and temporal properties of induction.
For example, the activity of V1 neurons can be modulated by light outside the
receptive field and as the modulation rate is increased response modulation falls
off more rapidly for large uniform areas than smaller areas. The conclusion we
draw from these experiments is that lightness appears to be computed slowly on
the basis of edge and context information. A possible role for the spatial
interactions is lightness constancy, which is thought to depend on extensive
spatial integration. We find not only that V1 responses are strongly context
dependent, but that this dependence makes V1 lightness constant on average. The
dependence of constancy on surround interactions underscores the fundamental role
that context plays in perception. In more recent studies, further support has
been found for the importance of context in experiments using natural scene
stimuli.
PMID- 17027384
TI - Beyond a relay nucleus: neuroimaging views on the human LGN.
AB - The lateral geniculate nucleus (LGN) is the thalamic station in the
retinocortical projection and has traditionally been viewed as the gateway for
sensory information to enter the cortex. Here, we review recent studies of the
human LGN that have investigated the retinotopic organization, physiologic
response properties, and modulation of neural activity by selective attention and
by visual awareness in a binocular rivalry paradigm. In the retinotopy studies,
we found that the contralateral visual field was represented with the lower field
in the medial-superior portion and the upper field in the lateral-inferior
portion of each LGN. The fovea was represented in posterior and superior
portions, with increasing eccentricities represented more anteriorly. Functional
MRI responses increased monotonically with stimulus contrast in the LGN and in
visual cortical areas. In the LGN, the dynamic response range of the contrast
function was larger and contrast gain was lower than in the cortex. In our
attention studies, we found that directed attention to a spatial location
modulated neural activity in the LGN in several ways: it enhanced neural
responses to attended stimuli, attenuated responses to ignored stimuli, and
increased baseline activity in the absence of visual stimulation. Furthermore, we
showed in a binocular rivalry paradigm that neural activity in the LGN correlated
strongly with the subjects' reported percepts. The overall view that emerges from
these studies is that the human LGN plays a role in perception and cognition far
beyond that of a relay nucleus and, rather, needs to be considered as an early
gatekeeper in the control of visual attention and awareness.
PMID- 17027386
TI - Finding a face in the crowd: parallel and serial neural mechanisms of visual
selection.
AB - At any given moment, our visual system is confronted with more information than
it can process. Thus, attention is needed to select behaviorally relevant
information in a visual scene for further processing. Behavioral studies of
attention during visual search have led to the distinction between serial and
parallel mechanisms of selection. To find a target object in a crowded scene, for
example a "face in a crowd", the visual system might turn on and off the neural
representation of each object in a serial fashion, testing each representation
against a template of the target object. Alternatively, it might allow the
processing of all objects in parallel, but bias activity in favor of those
neurons representing critical features of the target, until the target emerges
from the background. Recent neurophysiological evidence shows that both serial
and parallel selections take place in neurons of the ventral "object-recognition
pathway" during visual search tasks in which monkeys freely scan complex displays
to find a target object. Furthermore, attentional selection appears to be
mediated by changes in the synchrony of responses of neuronal populations in
addition to the modulation of the firing rate of individual neurons.
PMID- 17027387
TI - Saccades, salience and attention: the role of the lateral intraparietal area in
visual behavior.
AB - Neural activity in the lateral intraparietal area (LIP) has been associated with
attention to a location in visual space, and with the intention to make saccadic
eye movement. In this study we show that neurons in LIP respond to recently
flashed task-irrelevant stimuli and saccade targets brought into the receptive
field by a saccade, although they respond much to the same stimuli when they are
stable in the environment. LIP neurons respond to the appearance of a flashed
distractor even when a monkey is planning a memory-guided delayed saccade
elsewhere. We then show that a monkey's attention, as defined by an increase in
contrast sensitivity, is pinned to the goal of a memory-guided saccade throughout
the delay period, unless a distractor appears, in which case attention
transiently moves to the site of the distractor and then returns to the goal of
the saccade. LIP neurons respond to both the saccade goal and the distractor, and
this activity correlates with the monkey's locus of attention. In particular, the
activity of LIP neurons predicts when attention migrates from the distractor back
to the saccade goal. We suggest that the activity in LIP provides a salience map
that is interpreted by the oculomotor system as a saccade goal when a saccade is
appropriate, and simultaneously is used by the visual system to determine the
locus of attention.
PMID- 17027388
TI - Visual masking approaches to visual awareness.
AB - In visual masking, visible targets are rendered invisible by modifying the
context in which they are presented, but not by modifying the targets themselves.
Here I summarize a decade of experimentation using visual masking illusions in
which my colleagues and I have begun to establish the minimal set of conditions
necessary to maintain the awareness of the visibility of simple unattended
stimuli. We have established that spatiotemporal edges must be present for
targets to be visible. These spatiotemporal edges must be encoded by transient
bursts of spikes in the early visual system. If these bursts are inhibited,
visibility fails. Target-correlated activity must rise within the visual
hierarchy at least to the level of V3, and be processed within the occipital
lobe, to achieve visibility. The specific circuits that maintain visibility are
not yet known, but we have deduced that lateral inhibition plays a critical role
in sculpting our perception of visibility, both by causing interactions between
stimuli positioned across space, and also by shaping the responses to stimuli
across time. Further, the studies have served to narrow the number of possible
theories to explain visibility and visual masking. Finally, we have discovered
that lateral inhibition builds iteratively in strength throughout the visual
hierarchy, for both monoptic and dichoptic stimuli. Since binocular information
is not integrated until inputs from the two eyes reach the primary visual cortex,
it follows that the early visual areas contain differential levels of monoptic
and dichoptic lateral inhibitions. We exploited this fact to discover that
excitatory integration of binocular inputs occurs at an earlier level than
interocular suppression. These findings are potentially fundamental to our
understanding of all forms of binocular vision and to determining the role of
binocular rivalry in visual awareness.
PMID- 17027389
TI - Blindsight, conscious vision, and the role of primary visual cortex.
AB - What is the role the primary visual cortex (V1) in vision? Is it necessary for
conscious sight, as indicated by the cortical blindness that results from V1
destruction? Is it even necessary for blindsight, the nonreflexive visual
functions that can be evoked with stimuli presented to cortically blind fields?
In the context of this controversial issue, I present evidence indicating that
not only is blindsight possible, but that conscious vision may, to a varying
degree, return to formerly blind fields with time and practice even in cases
where functional neuroimaging reveals no V1 activation.
PMID- 17027390
TI - Chapter 13 Bilateral frontal leucotomy does not alter perceptual alternation
during binocular rivalry.
AB - When discrepant stimuli are presented to each eye and fusion is impossible,
perception spontaneously oscillates between the two patterns (binocular rivalry).
Functional MRI (fMRI) research identified a frontoparietal network in the right
hemisphere associated with perceptual transitions, and it has been proposed that
this network is at the origin of the perceptual alternations. Neuroimaging
results, however, do not imply causality and lesion studies are needed. Here, we
studied one patient who had most of the prefrontal cortex disconnected from the
rest of the brain after a bilateral frontal leucotomy. His performance in two
binocular rivalry tasks was indistinguishable from that of the controls. The
results indicate that prefrontal cortex is unnecessary for perceptual
alternations during binocular rivalry.
PMID- 17027392
TI - Combining visual and auditory information.
AB - Robust perception requires that information from by our five different senses be
combined at some central level to produce a single unified percept of the world.
Recent theory and evidence from many laboratories suggests that the combination
does not occur in a rigid, hardwired fashion, but follows flexible situation
dependent rules that allow information to be combined with maximal efficiency. In
this review we discuss recent evidence from our laboratories investigating how
information from auditory and visual modalities is combined. The results support
the notion of Bayesian combination. We also examine temporal alignment of
auditory and visual signals, and show that perceived simultaneity does not depend
solely on neural latencies, but involves active processes that compensate, for
example, for the physical delay introduced by the relatively slow speed of sound.
Finally, we go on to show that although visual and auditory information is
combined to maximize efficiency, attentional resources for the two modalities are
largely independent.
PMID- 17027393
TI - Crossmodal interactions: lessons from synesthesia.
AB - Synesthesia is a condition in which stimulation in one modality also gives rise
to a perceptual experience in a second modality. In two recent studies we found
that the condition is more common than previously reported; up to 5% of the
population may experience at least one type of synesthesia. Although the
condition has been traditionally viewed as an anomaly (e.g., breakdown in
modularity), it seems that at least some of the mechanisms underlying synesthesia
do reflect universal crossmodal mechanisms. We review here a number of examples
of crossmodal correspondences found in both synesthetes and nonsynesthetes
including pitch-lightness and vision-touch interaction, as well as cross-domain
spatial-numeric interactions. Additionally, we discuss the common role of spatial
attention in binding shape and color surface features (whether ordinary or
synesthetic color). Consistently with behavioral and neuroimaging data showing
that chromatic-graphemic (colored-letter) synesthesia is a genuine perceptual
phenomenon implicating extrastriate cortex, we also present electrophysiological
data showing modulation of visual evoked potentials by synesthetic color
congruency.
PMID- 17027394
TI - Integrating motion information across sensory modalities: the role of top-down
factors.
AB - Recent studies have highlighted the influence of multisensory integration
mechanisms in the processing of motion information. One central issue in this
research area concerns the extent to which the behavioral correlates of these
effects can be attributed to late post-perceptual (i.e., response-related or
decisional) processes rather than to perceptual mechanisms of multisensory
binding. We investigated the influence of various top-down factors on the
phenomenon of crossmodal dynamic capture, whereby the direction of motion in one
sensory modality (audition) is strongly influenced by motion presented in another
sensory modality (vision). In Experiment 1, we introduced extensive feedback in
order to manipulate the motivation level of participants and the extent of their
practice with the task. In Experiment 2, we reduced the variability of the
irrelevant (visual) distractor stimulus by making its direction predictable
beforehand. In Experiment 3, we investigated the effects of changing the stimulus
response mapping (task). None of these manipulations exerted any noticeable
influence on the overall pattern of crossmodal dynamic capture that was observed.
We therefore conclude that the integration of multisensory motion cues is robust
to a number of top-down influences, thereby revealing that the crossmodal dynamic
capture effect reflects the relatively automatic integration of multisensory
motion information.
PMID- 17027395
TI - Crossmodal audio-visual interactions in the primary visual cortex of the visually
deprived cat: a physiological and anatomical study.
AB - Blind individuals often demonstrate enhanced non-visual perceptual abilities.
Neuroimaging and transcranial magnetic stimulation experiments have suggested
that computations carried out in the occipital cortex may underlie these enhanced
somatosensory or auditory performances. Thus, cortical areas that are dedicated
to the analysis of the visual scene may, in the blind, acquire the capacity to
participate in other sensory processing. However, the neural substrate that
underlies this transfer of function is not fully characterized. Here we studied
the synaptic and anatomical basis of this phenomenon in cats that were visually
deprived by dark rearing, either early visually deprived after birth (EVD), or
late visually deprived after the end of the critical period (LVD); data were
compared with those obtained in normally reared cats (controls). The presence of
synaptic and spike responses to auditory stimulation was examined by means of
intracellular recordings in area 17 and the border between areas 17 and 18. While
none of the cells recorded in control and LVD cats showed responses to sound, 14%
of the cells recorded in EVD cats showed both subthreshold synaptic responses and
suprathreshold spike responses to auditory stimuli. Synaptic responses were of
small amplitude, but well time-locked to the stimuli and had an average latency
of 30+/-12ms. In an attempt to identify the origin of the inputs carrying
auditory information to the visual cortex, wheat germ agglutinin-horseradish
peroxidase (WGA-HRP) was injected in the visual cortex and retrograde labeling
examined in the cortex and thalamus. No significant retrograde labeling was found
in auditory cortical areas. However, the proportion of neurons projecting from
supragranular layers of the posteromedial and posterolateral parts of the lateral
suprasylvian region to V1 was higher than that in control cats. Retrograde
labeling in the lateral geniculate nucleus showed no difference in the total
number of neurons between control and visually deprived cats, but there was a
higher proportion of labeling in C-laminae in deprived cats. Labeled cells were
not found in the medial geniculate nucleus, a thalamic relay for auditory
information, in either control or visually deprived cats. Finally,
immunohistochemistry of the visual cortex of deprived cats revealed a striking
decrease in pavalbumin- and calretinin-positive neurons, the functional
implications of which we discuss.
PMID- 17027396
TI - The "other" transformation required for visual-auditory integration:
representational format.
AB - Multisensory integration of spatial signals requires not only that stimulus
locations be encoded in the same spatial reference frame, but also that stimulus
locations be encoded in the same representational format. Previous studies have
addressed the issue of spatial reference frame, but representational format,
particularly for sound location, has been relatively overlooked. We discuss here
our recent findings that sound location in the primate inferior colliculus is
encoded using a "rate" code, a format that differs from the place code used for
representing visual stimulus locations. Possible mechanisms for transforming
signals from rate-to-place or place-to-rate coding formats are considered.
PMID- 17027398
TI - Publication bias.
PMID- 17027399
TI - Sensitivity of routine 1.0-Tesla magnetic resonance imaging versus arthroscopy as
gold standard in fresh traumatic chondral lesions of the knee in young adults.
AB - PURPOSE: The purpose of this study was to evaluate the sensitivity, specificity,
and accuracy of routine 1.0-Tesla magnetic resonance imaging (MRI) versus
arthroscopy in detecting fresh traumatic chondral lesions of the knee. METHODS:
Over a period of 6 years, 578 consecutive military personnel underwent MRI before
arthroscopy of the knee. Of these, 32 patients with arthroscopically proven fresh
traumatic chondral lesions of the knee were chosen for further analysis. A
supplementary condition was that arthroscopy was performed no later than 6 weeks
after the onset of trauma. The original MRIs and hospital records were re
evaluated and the chondral lesions were graded and compared with arthroscopic
findings. The arthroscopic results served as the gold standard when the
sensitivity, specificity, and accuracy of MRI were calculated. RESULTS: The age
of the patients ranged from 19 to 21 years (mean, 19.6 years). MRI detected
cartilage defects with a sensitivity of 36% (95% confidence interval [CI], 23% to
50%), specificity of 91% (95% CI, 85% to 95%), and diagnostic accuracy of 78%
(95% CI, 72% to 83%). MRI results were affected by the grade of the chondral
lesions. CONCLUSIONS: This study shows that routine 1.0-T MRI is not sensitive
but is specific and somewhat accurate in detecting fresh traumatic articular
cartilage lesions. The hypothesis of this study was that 1.0-T MRI could replace
diagnostic arthroscopy in the diagnosis of fresh traumatic chondral lesions. Our
results fail to support this hypothesis because of the poor sensitivity obtained
with MRI. LEVEL OF EVIDENCE: Level II, development of diagnostic criteria.
PMID- 17027400
TI - Initial biomechanical properties of staple-anchor Achilles tendon allograft and
interference screw bone-patellar tendon-bone autograft fixation for anterior
cruciate ligament reconstruction in a cadaveric model.
AB - PURPOSE: Anterior cruciate ligament (ACL) reconstruction is a common procedure
that has a fairly high success rate. Despite such success, controversy exists
with regard to fixation and graft type. The purpose of this study was to quantify
the maximum load to failure for staple-anchor freeze-dried Achilles tendon
allograft fixation compared with interference screw bone-pattelar tendon-bone
autograft fixation at the time of insertion for ACL reconstruction. METHODS:
Eleven pairs of cadaveric knees were prepared for ACL reconstruction by
disarticulation before graft insertion. The tibia and femur were mounted
separately onto an MTS machine and were loaded to failure in line with the
tunnels. Femoral fixation for the allograft was provided by a staple anchor;
tibial fixation was provided by a suture anchor. Titanium interference screws on
the femoral and tibial sides provided autograft fixation. A paired t test was
performed to compare mechanical testing results in the 2 groups. RESULTS: Mean
maximum load to failure for the allograft was 58.7 N (range, 32.3 to 92.6 N) and
119.6 N (range, 82 to 165.9 N) for the femur and the tibia, respectively,
compared with 228.2 N (range, 74.2 to 352 N) and 232.9 N (range, 65.1 to 553.1 N)
for the autografts. This difference was statistically significant (P < .001) for
femoral fixation, but it was not statistically significant for tibial fixation (P
= .186). CONCLUSIONS: Soft tissue Achilles tendon allograft with staple fixation
is a significantly weaker fixation construct when compared with autograft bone
patellar tendon-bone with interference screw fixation. CLINICAL RELEVANCE: This
study shows significantly weaker fixation in the staple-alograft construct and
yet this construct has had at least equivalent results over a 5-year time frame,
indicating that rigid femoral fixation may not be a critical factor in long-term
results.
PMID- 17027401
TI - Assessment of reprocessed arthroscopic shaver blades.
AB - PURPOSE: The purpose of this study was to evaluate the level of contaminants on,
as well as the quality of, reprocessed shaver blades. METHODS: We assessed 7 new
shaver blades and 27 shaver blades that had been reprocessed with mechanical
cleaning, functional testing, and sterilization with ethylene oxide. A
spectrophotometer measured the amount of nucleic acid and protein. The blade
quality was assessed by photographing the blades with magnification and
determining the percentage of damage present on each blade. A subset of shaver
blades were then used to cut meniscal tissue, and the cut surface was measured
for smoothness by image processing and automated laser scanning cytometry. In
evaluation of the meniscus, for the subset of shavers, an image processing value
of 1 indicates a smooth, straight line, and values lower than 1 reflect
deviations in the cut surface (the closer the value is to 1, the smoother the
surface). Laser scanning cytometry values indicate the percentage of
irregularities in the cut surface (the lower the value is, the smoother the
surface). RESULTS: Of the 27 reprocessed shaver blades, 13 (48%) had detectable
levels of protein and 17 (63%) had detectable levels of nucleic acid. On the
reprocessed shaver blades, protein levels ranged from 2.43 microg to 60 microg
and nucleic acid levels ranged from 0.40 microg to 3.5 microg. No new shaver
blade had contaminants. Twenty reprocessed shaver blades had been manufactured
with teeth and could be evaluated for visible damage. Of these, 10 had 1% to 25%
damage, 5 had 26% to 50% damage, 3 had 51% to 75% damage, and 2 had 76% to 100%
damage. The new blades had no visible damage. Image processing revealed
smoothness of the surface cut with new shaver blades, yielding values of 1 +/-
0.12, whereas the values for reprocessed shaver blades ranged from 0.62 +/- 0.02
to 1 +/- 0.07. Laser scanning cytometry values ranged from 3.3% to 7.1% for the
new blades as compared with 5.8% to 20.0% for the reprocessed blades.
CONCLUSIONS: Of the reprocessed shaver blades, 48% had detectable levels of
protein and 63% had detectable levels of nucleic acid. All of the reprocessed
blades visually evaluated showed some level of damage or wear, whereas no new
blade had such damage. In addition, menisci cut with reprocessed shavers showed
rougher edges than did menisci cut with new shavers. CLINICAL RELEVANCE: To make
an informed decision regarding the use of reprocessed shaver blades, surgeons
will want to know the level of contamination on, and the quality of, reprocessed
shaver blades.
PMID- 17027402
TI - Self-reported patient outcomes at a minimum of 5 years after allograft anterior
cruciate ligament reconstruction with or without medial meniscus transplantation:
an age-, sex-, and activity level-matched comparison in patients aged
approximately 50 years.
AB - PURPOSE: Patient outcomes at a minimum of 5 years after medial meniscus
transplantation and primary anterior cruciate ligament (ACL) reconstruction via
allograft tissues were compared with those of age-, sex-, and activity level
matched patients who underwent meniscal repair or partial meniscectomy and
primary ACL reconstruction via allograft tissues. METHODS: Eight patients (mean
age, 51 +/- 5 years; three women and five men) at 5.5 +/- 0.5 years after medial
meniscus transplantation and ACL reconstruction (group 1) and eight matched
patients (mean age, 50 +/- 5 years; three women and five men) at 5.1 +/- 0.5
years after meniscal repair or partial meniscectomy and ACL reconstruction (group
2) completed the meniscus allograft clinical registry questionnaire, which
combined the modified Lysholm knee scoring scale, the 1999 International Knee
Documentation Committee subjective knee evaluation, and the knee pain level score
on a 10-cm visual analog scale. RESULTS: Both groups displayed similar
improvements in the modified Lysholm knee scoring scale components of pain, knee
stability, squatting, stair climbing, and limping, as well as overall score (P <
.05). Only group 2 displayed significant reductions in swelling. The groups
displayed similar improvements in the 1999 International Knee Documentation
Committee subjective knee evaluation components of sitting, rising from a chair,
running, jumping, and stopping quickly, as well as overall score (P < .05). They
also displayed significant improvements in the visual analog scale knee pain
level score; however, group 1, which displayed greater preoperative pain levels,
had considerably larger reductions. Most group 1 patients (7/8 [87.5%]) and all
group 2 patients (8/8 [100%]) considered their surgery to be a success and would
undergo the same procedure again if necessary. CONCLUSIONS: Although group 1 had
greater preoperative knee pain levels, their pain levels at 5 years
postoperatively were comparable to those in group 2. With the exception of
swelling, comparable improvements were observed between groups for all other
variables. LEVEL OF EVIDENCE: Level III, retrospective, case-control study.
PMID- 17027403
TI - Sutures and suture anchors--update 2006.
AB - PURPOSE: To evaluate recently introduced sutures and suture anchors for single
pull load to failure strength and failure mode. METHODS: Suture anchors were
tested in fresh porcine metaphyseal cortex and cancellous troughs with the use of
an established protocol. An Instron machine applied tensile loads parallel to the
axis of insertion at a rate of 12.5 mm/sec until failure, and mean anchor failure
strengths were calculated. The mode of failure (anchor pull-out, suture eyelet
cut-out, or suture failure) was recorded. Anchors tested included the BioRaptor
2.9, BioZip, Super Revo, Impact, Allograft cortical anchor, SpiraLok, Herculon,
AxyaLoop titanium anchors 3, 5, and 6.5 mm, AxyaLoop bioabsorbable anchors 3, 5,
and 6.5, ParaFix titanium anchors 3, 5, and 6.5, ParaSorb BioAnchors 3, 5.5, and
6.5, and Bio-Corkscrew FT. Sutures were also tested through an established
protocol for load to failure. Sutures tested consisted of Orthocord, Ultrabraid
(White and CoBraid), ForceFiber, Hi-Fi, MagnumWire, and Maxbraid Polyethylene
Plus. RESULTS: Mean failure loads were as follows: BioRaptor 238 N, BioZip 366 N,
double-loaded Super Revo 486 N, triple-loaded Super Revo 362 N, Impact 202 N,
Allograft cortical anchor 240 N, SpiraLok 289 N, Herculon 819 N, AxyaLoop
titanium anchors 3.0 (335 N), 5.0 (485 N), and 6.5 mm (465 N), AxyaLoop
bioabsorbable anchors 3 (143 N), 5 (395 N), and 6.5 (369 N), ParaFix titanium
anchors 3 (335 N), 5 (485 N), and 6.5 (465 N), ParaSorb BioAnchors 3 (143 N), 5.5
(395 N), and 6.5 (369 N), and Bio-Corkscrew FT (260 N). The sutures all broke at
the mid point of their tested strands away from the grips. Mean suture strength
for No. 2 Orthocord was 92 N; for No. 2 Ultrabraid CoBraid and White, strengths
were 265 N and 280 N, respectively; strength for No. 2 Force Fiber was 289 N, for
No. 2 Hi-Fi 250 N, for No. 2 MagnumWire 303 N, and for No. 2 Maxbraid
Polyethylene Plus 256 N. CONCLUSIONS: Newer suture products showed significant
improvements in load to failure values when compared with braided polyester
sutures. Higher load to failure values continue to be seen in metal versus
biodegradable anchors and in screw-type versus nonscrew designs. CLINICAL
RELEVANCE: Surgeons who prefer stronger sutures now have several high-strength
suture options from which to choose. Most of the new anchors tested performed
very well.
PMID- 17027404
TI - Evaluation of residual rotator cuff defects after in vivo single- versus double
row rotator cuff repairs.
AB - PURPOSE: As arthroscopic rotator cuff surgery has advanced, new techniques have
emerged to maximize the biomechanical strength of the repair construct. The
double-row repair has been recommended as a means of increasing the contact area
of the repaired rotator cuff to the native bone bed. This study attempts to
sequentially examine and measure the rotator cuff footprint (in vivo) before cuff
repair, after an initial lateral-row repair (before the medial-row sutures are
tied), and finally, after the double-row repair. In this way, the rotator cuff
footprint of single- and double-row repairs can be quantified and compared.
METHODS: Between October 2004 and February 2005, 26 patients were enrolled in the
study. These patients had rotator cuff tears that were amenable to double-row
repair by means of performing the lateral-row repair before the medial-row
repair. After preparation of the greater tuberosity footprint, the native
footprint was measured in the medial-to-lateral direction. Next, the medial-row
anchors and sutures were passed through the cuff (but not tied), and then the
lateral row was secured via suture anchors and the arthroscope was reinserted
into the intra-articular space. A depth gauge was introduced through the repaired
cuff (lateral row only), and the residual bare footprint was measured. The medial
row was then tied, and the cuff was again visualized from the intra-articular
position to measure any remaining bare footprint. RESULTS: The mean footprint
measured 17.0 +/- 1.9 mm from medial to lateral. After repair of the lateral row,
the mean residual uncovered footprint measured 9.0 +/- 2.0 mm. This constituted a
52.7% +/- 9.2% uncovered area after a single lateral-row repair. After the medial
row was secured, there were no remaining residual deficits of the cuff footprint.
CONCLUSIONS: After an isolated lateral-row repair, 52.7% +/- 9.2% of the rotator
cuff footprint remains uncovered. On average, the double-row repair offered over
twice the footprint coverage yielded by a single-row repair. CLINICAL RELEVANCE:
The arthroscopic shoulder surgeon should be aware of the enhanced footprint
coverage offered by double-row rotator cuff fixation as opposed to single-row
rotator cuff fixation.
PMID- 17027405
TI - The bear-hug test: a new and sensitive test for diagnosing a subscapularis tear.
AB - PURPOSE: It was our intent to devise a new clinical test that would more
accurately diagnose subscapularis tears than the current clinical tests. This new
test is called the bear-hug test. The purpose of this study was to assess the
bear-hug test and compare it with the current tests of subscapularis function
(lift-off, belly-press, and Napoleon tests). METHODS: Between January 2004 and
March 2004, 68 consecutive patients scheduled for an arthroscopic procedure were
evaluated preoperatively; the preoperative clinical examination findings were
then correlated with arthroscopic findings. Lift-off, belly-press, Napoleon, and
bear-hug tests were included in the examination. Furthermore, for the belly-press
and bear-hug tests, the strength was precisely quantified by means of an
electronic digital tensiometer (Kern HBC). Diagnostic arthroscopy was the
reference that determined the actual pathologic lesions. RESULTS: Subscapularis
tears occurred with a prevalence rate of 29.4%. Of the subscapularis tears, 40%
were not predicted by preoperative assessment by use of all of the tests. The
bear-hug test was found to be the most sensitive test (60%) of all of those
studied (belly-press test, 40%; Napoleon test, 25%; and lift-off test, 17.6%). In
contrast, all 4 tests had a high specificity (lift-off test, 100%; Napoleon test,
97.9%; belly-press test, 97.9%; and bear-hug test, 91.7%). No statistically
significant difference was found between the area under the receiver operating
characteristic curve of the bear-hug test and that of the belly-press test in
diagnosing a torn subscapularis. However, the areas under the receiver operating
characteristic curve for both the bear-hug test and the belly-press test were
significantly greater than those for the lift-off and Napoleon tests (P < .05).
Positive bear-hug and belly-press tests suggest a tear of at least 30% of the
subscapularis, whereas a positive Napoleon test indicates that greater than 50%
of the subscapularis is torn. Furthermore, a positive lift-off test is not found
until at least 75% of the subscapularis is torn. CONCLUSIONS: The bear-hug test
optimizes the chance of detecting a tear of the upper part of the subscapularis
tendon. Moreover, because the bear-hug test represents the most sensitive test,
it can be considered to be the most likely clinical test to alert the surgeon to
a possible subscapularis tear. Performing all of the subscapularis tests is
useful in predicting the size of the tear. LEVEL OF EVIDENCE: Level I, diagnostic
study: testing of previously developed criteria in a series of consecutive
patients with arthroscopy used as the criterion standard.
PMID- 17027406
TI - Osteochondral lesions of the talus: randomized controlled trial comparing
chondroplasty, microfracture, and osteochondral autograft transplantation.
AB - PURPOSE: The purpose of this study was to compare outcomes of chondroplasty
versus microfracture versus osteochondral autologous transplantation (OAT) in
patients with osteochondral lesions of the talus (OLT). METHODS: After
prospective sample size analysis, patients with symptomatic, recalcitrant Ferkel
class 2b, 3, and 4 OLT were randomized to chondroplasty, microfracture, or OAT
treatment groups. Outcomes were measured with use of the American Orthopaedic
Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (AHS), the Subjective
Assessment Numeric Evaluation (SANE) rating, Numeric Pain Intensity (NPI), and
magnetic resonance imaging (MRI). RESULTS: Eleven patients had chondroplasty, 10
ankles (9 patients) had microfracture, and 12 patients had OAT. Mean time to
follow-up was 53 months (range, 24 to 119 months). AHS scores showed no
differences at 12 and 24 months, and SANE ratings showed no differences at final
follow-up. NPI was significantly lower (P < .001) in chondroplasty and
microfracture cases as compared with OAT at 24 hours postoperatively. Pearson's
correlation analysis demonstrated an inverse relation between microfracture and
OAT groups in that better outcome was associated with smaller lesions, compared
with the chondroplasty group, which revealed mixed results with no particular
trend. MRI revealed incomplete fill and edema after chondroplasty or
microfracture and chondral gaps after OAT. CONCLUSION: Our results demonstrate no
difference between chondroplasty, microfracture, and OAT with regard to AHS and
SANE ratings in patients with OLT. However, NPI at 24 hours postoperatively was
significantly lower in patients who had chondroplasty and microfracture. LEVEL OF
EVIDENCE: Level I, Therapeutic study, high-quality randomized controlled trial
with no statistically significant differences but narrow confidence interval.
PMID- 17027407
TI - A retrospective review of bone tunnel enlargement after anterior cruciate
ligament reconstruction with hamstring tendons fixed with a metal round
cannulated interference screw in the femur.
AB - PURPOSE: To assess bone tunnel enlargement after anterior cruciate ligament (ACL)
reconstruction with the use of hamstring tendons fixed with a round cannulated
interference (RCI) screw in the femur. METHODS: A consecutive series of 30 ACL
reconstructions performed with hamstring tendons fixed with an RCI screw in the
femur and with staples via Leeds-Keio ligament in the tibia was retrospectively
reviewed. The clinical outcome was evaluated through the Lysholm score. Anterior
instability was tested by Telos-SE (Telos Japan, Tokyo, Japan) measurement. The
location and angle of each femoral and tibial tunnel were measured with the use
of plain radiographs, and bone tunnel enlargement greater than 2 mm detected any
time 3, 6, 12, and 24 months postoperatively was defined as positive. Each factor
(location and angle of the tunnels, sex, affected side, age, Lysholm score, and
Telos-SE measurement) was compared between enlarged and nonenlarged groups.
RESULTS: Positive enlargement of the bone tunnel (>2.0 mm) was observed in 36.7%
(11 of 30) on the femoral side and 33.3% (10 of 30) on the tibial side, and in 6
knees of both sides. Half of patients (15 of 30) had an enlarged tunnel on the
femoral or the tibial side until 1 year postoperatively. In most cases,
enlargement reached maximum at 6 months postoperatively. Female patients tended
to have an enlarged tunnel, especially on the femoral side (P < .05). Tunnel
enlargement was not correlated with location and angle of the tunnels. Moreover,
no difference was found in Lysholm score and Telos-SE measurement between
enlarged and nonenlarged groups, although the nonenlarged group tended to exhibit
higher Lysholm score and lesser instability. CONCLUSIONS: Bone tunnel enlargement
of the femoral or tibial side was observed in half of patients (6 in both sides,
5 only in the femur, and 4 only in the tibia) after ACL reconstruction was
performed with a hamstring tendon fixed with an RCI screw. Female patients had a
greater chance for enlargement of the femoral tunnel than did males. This
enlargement had no significant impact on patient activity and on anterior
instability of the knee 1 year after surgery. LEVEL OF EVIDENCE: Level IV,
Therapeutic case series.
PMID- 17027408
TI - Changes in knee laxity and ligament force after sectioning the posteromedial
bundle of the posterior cruciate ligament.
AB - PURPOSE: Our purpose was to evaluate the role of the posteromedial (PM) bundle of
the native posterior cruciate ligament (PCL) in restraining posterior tibial
translation and the effects of sectioning of the PM bundle on PCL forces.
METHODS: The PCL's femoral origin was mechanically isolated by use of a
cylindrical coring cutter, and a cap of bone containing the ligament fibers was
attached to a load cell that recorded resultant force in the ligament as the knee
was passively extended from 120 degrees to 0 degrees without and with simulated
tibial loading conditions. Anteroposterior laxity was also measured after load
cell installation. The PM bundle was cut at its femoral origin, and all tests
were repeated. RESULTS: Cutting the PM bundle produced small but statistically
significant increases in mean laxity at 0 degrees (+1.06 mm) and 10 degrees
(+0.83 mm) of flexion; mean laxities at 30 degrees, 45 degrees, 70 degrees, and
90 degrees were unchanged. Forces in the remaining anterolateral bundle were not
significantly different from those in the intact ligament for any mode of tibial
loading, with the exception of the valgus moment, where sectioning of the PM
bundle significantly reduced the PCL force at 0 degrees and 5 degrees of flexion.
CONCLUSIONS: The relatively small increases in mean laxity after cutting of the
PM bundle show that it plays a minor role in restraining posterior tibial
translation. The minor changes in ligament force profiles after cutting of the PM
bundle indicate that the remaining anterolateral bundle fibers continued to be
loaded in a near-normal fashion. CLINICAL RELEVANCE: This study helps to
elucidate the function of the PM bundle in the native PCL. Because only small
changes were seen in the biomechanical parameters tested, the rationale for
reconstructing this bundle of the PCL could be questioned.
PMID- 17027409
TI - Tunnel expansion after anterior cruciate ligament reconstruction with autogenous
hamstrings: a comparison of the medial portal and transtibial techniques.
AB - PURPOSE: The purpose of this study was to evaluate the effects of 2 techniques of
drilling the femoral tunnel in anterior cruciate ligament (ACL) reconstruction
(medial portal v transtibial) on tunnel expansion. METHODS: Autogenous hamstring
ACL reconstructions performed by the senior author between July 1998 and July
2004, with a minimum 6-month radiographic follow-up, using the transtibial
technique (41 patients) and the medial portal technique (34 patients), were
evaluated. All procedures were performed via an endoscopic technique with
identical postoperative rehabilitation and graft fixation. Lateral and 45 degrees
posteroanterior (PA) radiographs were obtained for each patient at a minimum of 6
months postoperatively. The sclerotic margins of the femoral and tibial tunnels
were measured at the widest dimension of the tunnel by 2 physicians and were
compared with the initially drilled tunnel size after correction for radiographic
magnification. Statistical analysis was performed to compare the 2 groups by use
of the independent-samples t test, with significance set at .05. RESULTS: The
mean percentage increase in the femoral tunnel was 38.20% +/- 17.76% for the
medial portal technique and 53.96% +/- 21.72% for the transtibial technique on
the PA view and 23.80% +/- 16.50% for the medial portal technique and 50.07% +/-
26.98% for the transtibial technique on the lateral view. This difference was
statistically significant on both PA and lateral views. The mean percentage
increase in the tibial tunnel was 31.81% +/- 14.39% for the medial portal
technique and 36.31% +/- 17.81% for the transtibial technique on the PA view and
27.70% +/- 15.25% for the medial portal technique and 30.11% +/- 18.98% for the
transtibial technique on the lateral view; however, these increases failed to
reach statistical significance on either view. CONCLUSIONS: Femoral tunnel
expansion for hamstring autologous ACL reconstructions is significantly lower for
the medial portal technique when compared with the conventional transtibial
technique. LEVEL OF EVIDENCE: Level III, retrospective, comparative therapeutic
study.
PMID- 17027410
TI - Mini-open arthroscopically assisted Bristow-Latarjet procedure for the treatment
of patients with anterior shoulder instability: a cadaver study.
AB - PURPOSE: The purpose of this study was to evaluate the arthroscopically assisted
Bristow-Latarjet procedure. The aim was to use arthroscopic guidance to assist in
positioning of the coracoid bone block onto the anterolateral aspect of the
glenoid. The feasibility of this technique and its efficacy, reproducibility, and
potential neurovascular complications were evaluated. METHODS: A minimally
invasive technique was used to harvest the coracoid bone block and the attached
coracobiceps tendon. A portal was created through the subscapularis muscle and,
under arthroscopic guidance, the anterior aspect of the glenoid was cleaned and
reamed before the bone block was placed. Cannulated screws (3.5 mm) were used to
fix the vertically oriented bone block to the glenoid. The size of the bone
block, its position on the glenoid, and its relation to the subscapularis tendon
and the musculocutaneous and axillary nerves were recorded. RESULTS: In all 5
cadavers, the bone block was well positioned and was fixed to the anteroinferior
part of the glenoid. No lesions of the cephalic vein or of the surrounding
neurovasculature were observed. CONCLUSIONS: This study demonstrated the safe and
effective use of this arthroscopically assisted technique for correct positioning
of the coracoid bone block at the anterolateral aspect of the glenoid in the
cadaveric shoulder. Arthroscopy facilitated adequate reaming of the anterior
glenoid and aided in optimal positioning of the bone block. CLINICAL RELEVANCE:
This cadaveric study highlights the advantages offered by an arthroscopically
assisted Bristow-Latarjet procedure, which optimizes positioning of the block and
ensures adequate reaming of the anterior glenoid, thereby potentially reducing
the risks of early nonunion and late arthritis--complications commonly associated
with the classical Bristow-Latarjet technique.
PMID- 17027411
TI - Reconstruction of lateral ligament with arthroscopic drilling for treatment of
early-stage osteoarthritis in unstable ankles.
AB - PURPOSE: The purpose of this study was to investigate the clinical, radiologic,
and arthroscopic results of lateral stabilization with reconstruction of the
lateral ligaments and cartilage regeneration with arthroscopic drilling for the
treatment of moderate osteoarthritis of the ankle with simultaneous lateral
instability of the ankle (LIA). METHODS: There were 16 cases with LIA, 7 of which
had stage 2 osteoarthritis of the ankle according to the radiographic
classification of Takakura et al. and 9 of which had stage 3 osteoarthritis.
Arthroscopic drilling was performed with a motorized drill for the chondral
defect, and anatomic reconstruction of the lateral ligament with an autologous
gracilis tendon graft was performed for LIA. Clinical, radiologic, and
arthroscopic evaluations were performed before surgery and at the most recent
follow-up. RESULTS: In stage 2 cases the mean score on the American Orthopaedic
Foot and Ankle Society ankle-hindfoot scale was 42.5 +/- 6.8 points before
surgery and 87.4 +/- 4.2 points at the most recent follow-up (P = .0002). In
stage 3 cases the mean score was 41.4 +/- 8.0 points before surgery and 61.2 +/-
7.4 points at the most recent follow-up (P = .0001). The talar tilt angles on
standard stress radiography in stage 2 cases were 17.4 degrees +/- 4.5 degrees
before surgery and 3.4 degrees +/- 0.9 degrees at the most recent follow-up (P =
.0009). In stage 3 cases the mean talar tilt angles were 18.2 degrees +/- 4.7
degrees before surgery and 3.6 degrees +/- 0.7 degrees at the most recent follow
up (P < .0001). In all cases the radiographic classification of Takakura et al.
was unchanged between assessments before surgery and at the most recent follow
up. With regard to arthroscopic findings at 1 year after surgery, the
International Cartilage Repair Society's cartilage repair assessment score showed
6 nearly normal and 1 abnormal stage 2 cases and 1 abnormal and 8 severely
abnormal stage 3 cases. CONCLUSIONS: Reconstruction of the lateral ligament with
arthroscopic drilling as a surgical procedure for the treatment of stage 2
osteoarthritis with LIA can be recommended. LEVEL OF EVIDENCE: Level IV,
therapeutic case series.
PMID- 17027412
TI - Open and arthroscopic treatment of multidirectional instability of the shoulder.
AB - Multidirectional instability of the shoulder can be a difficult diagnostic and
therapeutic dilemma for orthopaedic surgeons. First described by Neer and Foster,
the mainstay of treatment is usually conservative, with most patients doing very
well with nonoperative management. In patients with recalcitrant symptoms,
surgical treatment primarily has been aimed at addressing the pathologically
increased capsular volume. Newer studies suggest that the pathology also includes
abnormal labral morphology and perhaps inadequate neuromuscular control. The
arthroscopic treatment of multidirectional instability has come to have
comparable results to open techniques when the multifactorial nature of the
disease is recognized and the multiple techniques are used in combination to
fully treat all pathology. Thermal capsulorrhaphy cannot be recommended at this
time, except perhaps as an adjunct to other capsular plication or capsulorrhaphy
techniques. The advantages of a less invasive procedure make arthroscopic
capsular plication attractive, but it is associated with increased technical
difficulty and a steep learning curve. Further studies are needed to distinguish
a clear advantage of one over the other. Regardless of the technique used, the
key to success is addressing the capsular laxity and redundancy to restore
anatomic capsuloligamentous tension without overconstraining the shoulder.
PMID- 17027413
TI - Meniscal repair for anterior horn tear of the lateral meniscus.
AB - This technical note describes all-inside meniscal repair for anterior horn tears
of the lateral meniscus. A modified anteromedial portal is created for use in
visualizing the anterior horn of the lateral meniscus. A crescent-shaped suture
hook loaded with a polydioxanone suture (PDS) is inserted through an
anterolateral portal. The hook tip penetrates the meniscal peripheral rim and
advances across the tear. The suture hook penetrates the mobile central fragment.
A leading limb of the PDS is advanced into the knee joint. Then, the leading limb
of the suture is retrieved back to the anterolateral portal. With 2 limbs of PDS,
endoscopic knot tying is done. With this simple technique, vertically oriented
all-inside meniscal repair of an anterior horn tear of the lateral meniscus with
the use of absorbable suture materials is easily performed.
PMID- 17027414
TI - The accessory posteromedial portal revisited: utility for arthroscopic rotator
cuff repair.
AB - Arthroscopic rotator cuff repair is a technically challenging procedure.
Accessory arthroscopic portals have been described that allow for optimal suture
anchor placement, suture management, and knot tying. We describe here the
usefulness of an accessory posteromedial portal that facilitates direct suture
retrieval through the posterior aspect of a rotator cuff tear. This portal is
created approximately 4 to 5 cm medial to the posterolateral corner of the
acromion and 2 cm inferior to the scapular spine. The accessory posteromedial
portal is especially useful when a retracted tear of the infraspinatus or teres
minor is encountered. Because these tendons retract in a posterior and medial
direction, the accessory posteromedial portal places the tendon-penetrating
device in an ideal position for suture passage through the posterior portion of
the rotator cuff tear. This portal also allows placement of margin convergence
sutures for large U-shaped or L-shaped tears by permitting a direct "hand-off" of
the suture to or from a second penetrating device that is placed through a
standard anterior portal. If multiple suture anchors are required (as in the case
of large or massive cuff tears, or when double-row fixation is employed), sutures
can be pulled out through the accessory posteromedial portal to facilitate suture
management.
PMID- 17027415
TI - The "cruciate suture" for arthroscopic meniscal repair: a new technique.
AB - Meniscal repair has become the treatment of choice whenever a reparable tear is
diagnosed. Fixation strength of the repair technique is always of paramount
importance in comparison of various techniques, especially after the evolution of
many arthroscopic all-inside devices. We present a new arthroscopic meniscal
repair suturing technique called "cruciate suture." One 18-gauge needle and
suture material are used. The needle is loaded with the suture material from its
tip. The suture is folded at the tip of the needle, which is inserted to
penetrate the skin obliquely to appear inside the joint, making a loop. The
needle is retracted, while the suture is kept inside of it. The needle is
reinserted at the same hole, appearing inside the joint and making a second loop.
The needle is retracted completely. With the use of a probe, the loop at the
second point is pulled through the loop at the first point, thereby forming a
free end. The 2 limbs of the loop are pulled, thus driving the limb with the free
end outside of the joint. The first oblique vertical suture is completed at this
point. The needle is reloaded by the suture limb from the first point. The
previous procedure is repeated, with use of the second skin hole and the third
and fourth points to make the second oblique vertical suture. The cruciate suture
is now complete. We tested the ultimate tension load (UTL) of the cruciate suture
in comparison with that of the vertical suture (the gold standard). A total of 36
tests (18 for the cruciate suture and 18 for the vertical suture) were performed
on human menisci. The mean UTL of the cruciate suture was measured at 110 N; the
mean UTL of the vertical suture was 67 N.
PMID- 17027416
TI - Arthroscopic technique for patch augmentation of rotator cuff repairs.
AB - The patient is placed in the lateral position, and an arthroscopic cuff repair is
performed according to standard techniques. The line of repair is usually in the
shape of a "T" or an "L." The repair is viewed through the lateral portal, with
fluid inflow through the scope. Mattress sutures are placed in the anterior and
posterior portions of the cuff, with respect to the line of repair, just medial
to the most medial point of the tear. The sutures are placed in accordance with
margin convergence suture passing methods. Next, 2 double-stranded suture anchors
are placed into the lateral aspect of the greater tuberosity, which can be used
to secure the anterior and posterior portions of the rotator cuff as well as the
patch. The cuff sutures are tied first; then, the patch is addressed. The graft
is sized by placement of a ruled probe or similar device into the subacromial
space. The length of each side of the "rectangle" is measured to obtain the
dimensions of the patch. The patch is then cut to fit the measurements. If the
patch material is elastic, a slightly smaller than measured graft is cut to
provide tension on the repair. The arthroscope is then moved to the posterior
portal, and a large (8 mm) cannula, with a dam, is placed into the lateral
portal. All sutures are brought out of the lateral cannula, and corresponding
ends of each suture are held together in a clamp. The sutures are placed in their
respective orientations once outside the cannula (e.g., anterior-medial, anterior
lateral), covering all 4 quadrants. Care is taken to ensure that the sutures have
no twists and are not wrapped around one another. The sutures are passed through
the graft, in mattress fashion, with a free needle, in their respective corners
and clamped again. The graft is then grasped with a small locking grasper on its
medial edge and is passed through the cannula into the subacromial space. The
clamps holding the sutures are then gently pulled to remove the slack. A smaller
(5 mm) cannula is placed through 1 of the anchor incisions into the subacromial
space. The medial 2 sutures are retrieved, a pair at a time, through the small
cannula and are tied according to standard arthroscopic techniques; then, the
lateral 2 sutures are retrieved from the anchor. The graft should cover the area
of repair completely and should be under slight tension. Additional sutures may
be placed to further secure or tension the graft as necessary, with the use of
standard suture passing techniques, similar to those used when margin convergence
is performed. Passive shoulder motion, pendulum exercises, and active elbow and
wrist motion begin 2 days after surgery when the dressing is removed. Active
assisted motion and active motion begin at 6 weeks, with integrated periscapular
stabilization exercises. Formal cuff strengthening begins no sooner than 12 weeks
after surgery for large and massive tears.
PMID- 17027417
TI - Trans-cuff portal for arthroscopic posterior capsulorrhaphy.
AB - Arthroscopic repair of posterior shoulder instability is becoming an accepted
method of treatment. Most surgeons perform this procedure with the patient in a
lateral decubitus position to facilitate access to the posterior glenoid. We have
developed an accessory portal placed through the midportion of the rotator cuff
that allows easy and complete viewing of the posterior glenohumeral joint when
the patient is in a beach chair position and does not require the use of
traction. This portal provides a superior-to-inferior view of the posterior
glenoid rim and capsule and allows use of anterior and posterior routine portals
for posterior Bankart repair. In this study, the technique of posterior labral
repair in the beach chair position with use of the trans-cuff portal is
described, and preliminary results in 5 patients at an average follow-up of 24
months are presented. Through this approach, we were able to place 3 anchors,
with the lowest at the 7 o'clock position (for a right shoulder), in all
patients. Mean American Shoulder Elbow Surgeons (ASES) score improved from 53 +/-
15 preoperatively to 87 +/- 8 postoperatively (P < .01). All patients had an
excellent result with complete resolution of pain and instability.
PMID- 17027418
TI - Calcific tendonitis of the subscapularis tendon causing subcoracoid stenosis and
coracoid impingement.
AB - Calcific tendonitis is a common disease of the shoulder which usually responds to
conservative treatment. In cases unresponsive to conservative management,
arthroscopic treatment is sometimes required. While there are several reports on
calcifications within the supraspinatus tendon, documented cases involving the
subscapularis tendon are rare. We present a case of a 47 year old farmer with
recurrent anterior shoulder pain. An MRI revealed calcium deposits as well as a
large subcoracoid cyst. Arthroscopic excision of the multiple calcific deposits
left a large defect in the subscapularis tendon which was repaired back to the
lesser tuberosity using arthroscopic techniques. A coracoplasty resulted in an
increased coracohumeral space. The patient followed a conservative postop
rehabilitation protocol and ultimately regained full strength and was pain free
at the latest follow-up. We postulate two possible etiologies of subscapularis
calcific tendonitis: either an idiopathic calcific tendonitis caused a secondary
coracoid impingement or a primary subcoracoid stenosis resulted in an
interstitial subscapularis tear which eventually resulted in calcium deposition.
This report describes the clinical and technical details of arthroscopic excision
of calcific deposits of the subscapularis tendon as well as arthroscopic repair
of the resulting subscapularis defect.
PMID- 17027419
TI - Arthroscopic debridement and irrigation of periprosthetic total elbow infection.
AB - We report on a case of arthroscopic treatment of septic arthritis of the elbow
joint in a 65-year-old man with an elbow endoprosthesis. Two months after
arthroplasty of the elbow joint, the patient developed acute septic arthritis of
the right elbow. Methicillin-sensitive Staphylococcus aureus was identified as
the causative organism. Six days after the onset of symptoms, the patient was
treated with a single arthroscopic procedure of the infected periprosthetic
joint, including irrigation with 5 L of Ringer's lactate solution, debridement,
and partial synovectomy with a 4.5-mm curved shaver. Intravenous antibiotic
therapy was also used for 3 months including rifampicine and fucidic acid
according to the intraoperative cultures. The acutely infected total elbow
arthroplasty could be cured without removal of the endoprosthesis of the elbow.
Ten months postoperatively, the patient remains free of symptoms and his blood
rates are within normal limits.
PMID- 17027420
TI - Incidences of frostbite in arthroscopic knee surgery postoperative cryotherapy
rehabilitation.
AB - A retrospective study of 4 cases of frostbite was undertaken to examine causes
and to identify related contributory behaviors and circumstances. These patients
underwent various surgical interventions before the onset of frostbite during
similar postoperative care regimens. Surgical procedures included some of the
following in each patient: lateral retinacular release, vastus medialis oblique
muscle advancement, partial medial meniscectomy, chondromalacia patella,
trochlea, medial and lateral femoral condyle debridement, lateral retinaculum
release, and excision of medial plica. The mechanism of onset, development, and
sites of frostbite were uniform in all patients. In every case, the sites were
located in the area on top of the patella including some adjacent regions
depending on the size of each injury. Frostbite locations were correlated with
the part of the cryotherapy cold cuff device located on top of the patellar
region. This cuff portion was originally designed to accommodate surgical trauma
induced during autogenous bone-tendon-bone graft harvest in anterior cruciate
ligament reconstruction surgery. Locating cryotherapy over this region assisted
in minimizing pain and effusion for patients subsequent to distal patella bone
plug harvest trauma. However, the requirement for use of the pad in the patella
area for patients not undergoing anterior cruciate ligament reconstruction with
autograft was found to be unnecessary and was the primary cause of frostbite in
the cases presented here.
PMID- 17027421
TI - Why are so few randomized trials useful, and what can we do about it?
PMID- 17027422
TI - The Trial Protocol Tool: The PRACTIHC software tool that supported the writing of
protocols for pragmatic randomized controlled trials.
AB - OBJECTIVE: To develop a tool that would make it easier for researchers,
especially those in low- and middle-income countries, to write research protocols
for pragmatic randomized controlled trials. STUDY DESIGN AND SETTING: A series of
focus groups was held at the inaugural meeting of the Pragmatic RAndomized
Controlled Trials in Health Care (PRACTIHC) project in 2001 to develop a desired
specification for the Trial Protocol Tool. A working group of five individuals
from the PRACTIHC group was formed to develop content for the tool. RESULTS: The
Trial Protocol Tool was developed in English and Spanish as a Microsoft Windows
HTML help system. A Web-based version is also available. This main body of the
tool provides information, advice, and resources about the major headings that
should be part of every research protocol. Illustrative examples are used
throughout and are taken directly from the tool's protocol library. Additional
resources include checklists, programs (e.g., a sample size calculator), and
example documents (e.g., patient information leaflets). CONCLUSION: The Trial
Protocol Tool packages all the key requirements for the development of a research
protocol into one resource. We believe that the use of the tool will help
researchers to design effective trials and to write high-quality protocols.
PMID- 17027423
TI - Recommendations for reporting randomized controlled trials of herbal
interventions: Explanation and elaboration.
AB - Controlled trials that use randomized allocation are the best tool to control for
bias and confounding in trials testing clinical interventions. Investigators must
be sure to include information that is required by the reader to judge the
validity and implications of the findings in the reports of these trials. In
part, complete reporting of trials will allow clinicians to modify their clinical
practice to reflect current evidence toward the improvement of clinical outcomes.
The consolidated standards of reporting trials (CONSORT) statement was developed
to assist investigators, authors, reviewers, and editors on the necessary
information to be included in reports of controlled clinical trials. The CONSORT
statement is applicable to any intervention, including herbal medicinal products.
Controlled trials of herbal interventions do not adequately report the
information suggested in CONSORT. Recently, reporting recommendations were
developed in which several CONSORT items were elaborated to become relevant and
complete for randomized controlled trials of herbal medicines. We expect that
these recommendations will lead to more complete and accurate reporting of herbal
trials. We wrote this explanatory document to outline the rationale for each
recommendation and to assist authors in using them by providing the CONSORT items
and the associated elaboration, together with examples of good reporting and
empirical evidence, where available, for each. These recommendations for the
reporting of herbal medicinal products presented here are open to revision as
more evidence accumulates and critical comments are collected.
PMID- 17027424
TI - Claude Bernard was a 19th century proponent of medicine based on evidence.
AB - The French physiologist Claude Bernard (1813-1878) has the unfair reputation of
being ferociously opposed to the use of probabilities and statistics in medicine.
In the 19th century, he would have been included among those who opposed the
emergence of what would eventually become clinical epidemiology. The truth is
that Bernard valued the role of medical statistics in clinical medicine but
viewed it as potentially misleading in laboratory-based physiology. He posited
that clinical medicine had to be guided by probabilistic evidence as long as
physiological mechanisms remained unknown. Bernard praised the clinical
researches of Pierre Louis aiming to assess the efficacy of bloodletting in the
treatment of pneumonitis. The real objects of Bernard's contempt were the
physicians who pretended that medicine was an art strictly based on intuition and
tact and who pretended that comparative trials and statistics were useless for
clinical medicine. Overall, Bernard was a strong and explicit proponent of the
importance of scientific evidence in medical knowledge, be it from experiments or
from comparative trials.
PMID- 17027425
TI - Recurrent events counted in evaluations of predictive accuracy.
AB - OBJECTIVES: To describe an alternate approach for the calculation of sensitivity
and specificity when analyzing the accuracy of screening tools, which can be used
when standard calculations may be inappropriate. Sensitivity(ER) (ER denoting
event rate) is the number of events correctly predicted, divided by the total
number of events. Specificity(ER) is the amount of time that study participants
are predicted to be event negative, divided by the total amount of participant
observed time. Variance estimates for these statistics are constructed by
bootstrap resampling, taking into account event dependence. METHODS: Standard and
alternate approaches for calculating sensitivity and specificity were applied to
hospital falls risk screening tool data. In this application, the outcome of
interest was a recurrent event, there were multiple applications of the screening
tool, delays in screening tool completion, and patients' follow-up durations were
unequal. RESULTS: Application of sensitivity(ER) and specificity(ER) to this data
not only provided a clearer description of the screening tool's overall accuracy,
but also allowed examination of accuracy over time, accuracy in predicting
specific event numbers, and evaluation of the added value that screening tool
reapplications may have. CONCLUSION: Sensitivity(ER) and specificity(ER) provide
a valuable approach to screening tool evaluation in the clinical setting.
PMID- 17027426
TI - Empirical-Bayes adjustment improved conventional estimates in postmarketing drug
safety studies.
AB - OBJECTIVES: Empirical-Bayes adjustment was used to investigate the effects of
antibacterials on risk of arrhythmia in a large cohort study based upon automated
record linkage. STUDY DESIGN AND SETTING: The Prescription Drug Database of the
Varese Province, Italy, was used to form a population-based cohort of patients
who received at least one prescription of antibacterials for systemic use. All
cohort members were followed-up from the beginning of each antibacterial
therapeutic cycle up to 60 days afterward, identifying the first prescription of
an antiarrhythmic drug and/or the first admission for arrhythmia. Standardized
incidence ratios for eight classes of antibacterials, as well as for the specific
antibacterial drugs, were estimated using both conventional methods and empirical
Bayes (EB) adjustment. RESULTS: Using EB adjustment, overall precision was
greatly enhanced compared to the conventional analysis. Statistical evidence of
drug-induced dysrhythmic events was found for 17 drugs mostly belonging to
Macrolides and Quinolones. Strongest proarrhythmic effects were found for
Ciprofloxacin (standardized incidence ratio [SIR]: 1.98; 95% CI: 1.67, 2.34) and
Erythromycin (SIR: 1.91; 95% CI: 1.20, 2.88). CONCLUSION: Empirical-Bayes may
mitigate some problems inherent the conventional analysis. Macrolides and
Quinolones were associated with the highest number of positive signals of
dysrhythmic events. This requires further investigation by other types of
epidemiologic studies.
PMID- 17027427
TI - A comparison of two consensus methods for classifying morbidities in a single
professional group showed the same outcomes.
AB - OBJECTIVE: To investigate whether consensus differs when reached by the Nominal
or the Delphi method. STUDY DESIGN AND SETTING: Seventeen general practices from
North Staffordshire, England were randomly allocated to Delphi (postal feedback
only) or Nominal group (also had group discussion). General practitioners
classified 56 morbidities according to four scales of severity (chronicity, time
course, health care use, patient impact) in two consensus rounds. Consensus
outcomes were assessed by between-group comparison of severity scores at baseline
and follow-up rounds, and consensus process by within-group change in the
variance of severity scores between the two rounds. RESULTS: Consensus rounds
were completed by 21 out of 35 Nominal GPs and 23 out of 43 Delphi GPs. Baseline
scores for three of the four severity scales were significantly higher for
Nominal compared to Delphi GPs, but there were no differences at follow-up.
Between the two rounds, variance reduced within the Nominal and Delphi group,
respectively, by 61% and 35% (chronicity), 40% and 62% (time course), 42% and 36%
(health care use), and 19% and 38% (patient impact). CONCLUSION: The Nominal and
Delphi methods did not result in different outcomes and we conclude that either
method can be used in health services research.
PMID- 17027428
TI - Computer adaptive testing improved accuracy and precision of scores over random
item selection in a physical functioning item bank.
AB - BACKGROUND AND OBJECTIVE: Measuring physical functioning (PF) within and across
postacute settings is critical for monitoring outcomes of rehabilitation;
however, most current instruments lack sufficient breadth and feasibility for
widespread use. Computer adaptive testing (CAT), in which item selection is
tailored to the individual patient, holds promise for reducing response burden,
yet maintaining measurement precision. We calibrated a PF item bank via item
response theory (IRT), administered items with a post hoc CAT design, and
determined whether CAT would improve accuracy and precision of score estimates
over random item selection. METHODS: 1,041 adults were interviewed during
postacute care rehabilitation episodes in either hospital or community settings.
Responses for 124 PF items were calibrated using IRT methods to create a PF item
bank. We examined the accuracy and precision of CAT-based scores compared to a
random selection of items. RESULTS: CAT-based scores had higher correlations with
the IRT-criterion scores, especially with short tests, and resulted in narrower
confidence intervals than scores based on a random selection of items; gains, as
expected, were especially large for low and high performing adults. CONCLUSION:
The CAT design may have important precision and efficiency advantages for point
of-care functional assessment in rehabilitation practice settings.
PMID- 17027429
TI - Longer response scales improved the acceptability and performance of the
Nottingham Health Profile.
AB - OBJECTIVE: To test alternative response formats for the Nottingham Health Profile
(NHP), in terms of acceptability, score distributions, and measurement
properties. STUDY DESIGN AND SETTINGS: Randomized trial of four response formats
for the NHP: original "yes/no" format, a 3-point similarity format ("applies
completely/in part/not at all"), a 5-point intensity format ("completely true" to
"completely false"), and a 5-point frequency format ("all the time" to "never").
Respondents were patients discharged from a hospital. We compared scores
distributions, reliability coefficients, correlations with dimension-specific
numerical scales, and patient ratings of the instrument. RESULTS: Response rates
were similar for the four versions. The original response format had the fewest
fully completed questionnaires, and the largest ceiling effects. Internal
consistency and test-retest coefficients were acceptable for all versions, but
were higher for the two 5-point formats. Correlations reflecting convergent and
discriminant validity were higher for the longer response formats than for the
original version. The frequency format received the highest ratings from
patients, particularly from the sicker and older subgroups. CONCLUSIONS: The
psychometric performance and patient acceptability of the NHP can be improved by
using a 5-point frequency response format instead of the original dichotomous
response format.
PMID- 17027430
TI - Heritabilities and shared environmental effects were estimated from household
clustering in national health survey data.
AB - OBJECTIVES: The relative contributions of genetic and environmental variables to
within-household clustering of quantitative traits in household surveys are
poorly characterized. We estimated shared genetic and shared environmental
contributions to within-household correlation for anthropometric variables and
cardiovascular disease risk factors. STUDY DESIGN AND SETTING: Data were analyzed
for the Health Survey for England 1998, a representative national household
survey. Two-generation pedigrees were defined using information for relationships
within households. After standardizing for age and sex, data were analyzed for 11
quantitative traits. Variance components models were fitted to estimate the
proportion of variance due to additive genetic variance or shared environmental
effects. RESULTS: Within-household correlation coefficients for all related and
unrelated subjects ranged from 0.10 for C-reactive protein to 0.31 for height.
Pairwise correlations between related individuals within households were
consistently higher than those between unrelated individuals. Estimated
heritability ranged from 6% for diastolic blood pressure to 40% for serum
cholesterol. The proportion of variance attributable to shared environmental
effects ranged from 8% for cholesterol to 24% for height. CONCLUSION: In this
large, representative national sample of generally small families, estimates for
heritability were generally lower than previously reported, whereas the
contribution of shared environment and individual-level variation were greater.
PMID- 17027431
TI - A new method of analysis enabled a better understanding of clinical practice
guideline development processes.
AB - OBJECTIVE: To describe the process by which various forms of evidence are
discussed, valued, and interpreted within the process of developing evidence
based clinical practice guidelines and, in so doing, to develop a method for such
studies. STUDY DESIGN AND SETTING: An observational study. Two guideline
development groups were observed by a nonparticipant observer. The 21 meetings
were recorded, transcribed, and analyzed using grounded theory and frame
analysis. Qualitative analysis was complemented with descriptive statistics.
RESULTS: The groups organized their discussion around four domains--'science',
'practice', politics', and 'process'--and used boundary work to mediate between
these domains. Both groups spent most time discussing 'science', followed by
'practice' or its relation with 'science'. CONCLUSION: Our analysis offers an
innovative, replicable method of analysis of guideline development that permits
the identification of the proportions and interrelations between knowledge
domains deployed by guideline groups. This analysis also suggests that the
participation hierarchy observed here and by others might be an effect of the
imbalanced use of knowledge domains in the construction of clinical guidance.
This constitutes an important framework to understand the interplay of
participants and knowledge in guideline development.
PMID- 17027432
TI - Prediction of asthma in young adults using childhood characteristics: Development
of a prediction rule.
AB - OBJECTIVE: To develop an easily applicable prediction rule for asthma in young
adulthood using childhood characteristics. METHODS: A total of 1,055 out of 1,328
members of a Dutch birth cohort were followed from 2 to 21 years of age.
Univariate and multivariate logistic regression analyses were used to evaluate
the predictive value of childhood characteristics on asthma at 21 years of age. A
prognostic function was developed, and the area under the receiving operating
characteristic (ROC) curve was used to estimate the predictive ability of the
prognostic models. RESULTS: Of the 693 responding subjects, 86 (12%) were
diagnosed with asthma. Independent prognostic factors at ages 2 and 4 years were
female gender (odds ratios (OR) 1.9 and 2.1; 95% confidence intervals (CI) 1.2
3.2 and 1.3-2.5), smoking mother (OR 1.6 and 1.6; CI 1.0-2.7 and 1.0-2.6), lower
respiratory tract illness (OR 1.9 and 2.4; CI 1.0-3.6 and 1.4-4.0), and atopic
parents (OR 2.1 and 1.9; CI 1.3-3.4 and 1.2-3.1). The predictive power of both
models was poor; area under ROC curve was 0.66 and 0.68, respectively.
CONCLUSION: Asthma in young adulthood could not be predicted satisfactorily based
on childhood characteristics. Nevertheless, we propose that this method is
further tested as a tool to predict development of asthma.
PMID- 17027433
TI - Health problems were the strongest predictors of attrition during follow-up of
the GAZEL cohort.
AB - BACKGROUND AND OBJECTIVES: This study examined socioeconomic, lifestyle, and
health factors associated with response to annual mail questionnaires in a
longitudinal study from 1990 through 2000 within the French GAZEL cohort.
METHODS: Twenty thousand six hundred twenty-four participants volunteered in
1989, and received each year a questionnaire. As responding one given year was
not independent of responding in other years, mixed models were used to analyze
the variables associated with response. RESULTS: Higher response rates were
associated with gender (male), age (older), managerial status, and retirement.
Smoking and alcohol drinking at baseline were associated with lower
participation. Subjects who had at least three sick leaves were less likely to
respond, especially for absence for psychiatric and alcohol-related diseases
among men. Those who had rated their health as bad at baseline were less prone to
respond during the follow-up. Attrition in subsequent response to questionnaires
was associated with cancer diagnosis and with episodes of coronary heart disease
for men. CONCLUSION: Most of the variables that predicted initial participation
were also associated with continued participation during follow-up. Health
problems strongly predicted attrition, whereas socioeconomic factors played a
weaker role. Withdrawing is a reversible state and considering only one episode
of nonparticipation could be misleading.
PMID- 17027434
TI - A low tension between individual and societal time aspects in health improved
outcomes.
AB - OBJECTIVES: To review intertemporal choices, involving decisions with a trade-off
between something now and something later. These choices are common in health
both at an individual and societal level. METHODS: The present value of an
outcome, for example, the amount of money or the health outcomes in various
aspects, is equivalent to the value of a future outcome discounted with the delay
of time. The concept of diminishing value over time is positive discounting.
Economic forecasts generally use discount rates in which the value of a future
dollar is less than the value of a present dollar, and where the discount rates
are similar for the individual investor and society. The value of future health
is commonly thought of as similar to the value of future money. Yet, the
individual may rationally choose a discount rate that is exceedingly low or even
negative. This paradox is particularly relevant when considering primary and
secondary prevention, where initial and continuing costs may precede beneficent
outcomes by decades, making discount rate selections the dominant factor in
determining decisions. CONCLUSION: We suggest that the societal perspective
should also recognize that discount rates for health outcomes are largely
irrelevant and that even negative discount rates have crucial relevance.
PMID- 17027435
TI - Response to Carter et al.: A survey identified publication bias in the secondary
literature.
PMID- 17027437
TI - Nutrition and soccer: a primer.
PMID- 17027436
TI - Oily fish reduces plasma triacylglycerols: a primary prevention study in
overweight men and women.
AB - OBJECTIVE: Previous studies have demonstrated benefits of high-dose long-chain
omega-3 polyunsaturated fatty acid (LC omega-3 PUFA) supplements on metabolic
risk. Effects of increased dietary omega-3 PUFA, via oily fish and/or plant
derived omega-3 PUFAs, are less clear and may be modulated by the omega-6:omega-3
PUFA of the habitual diet. This study examined the effect on cardiovascular
disease risk markers of reducing dietary omega-6:omega-3 PUFA by changes in
linoleic acid:alpha-linolenic acid (LA:LNA) and/or increasing LC omega-3 PUFA. It
tested whether decreases in LA:LNA modulate effects of LC omega-3 PUFA. METHODS:
One hundred forty-two subjects, recruited to a 24-wk randomized study, were
assigned to a control group or one of four interventions. Intervention groups
received two portions of oily fish (4.5 g eicosapentaenoic acid + docosahexanoic
acid) or white fish (0.7 g eicosapentaenoic acid + docosahexanoic acid) per week,
and replaced habitual household fats with ones high in sunflower (high LA:LNA) or
rapeseed (low LA:LNA) oil. RESULTS: Modest dietary manipulations of omega-6 and
omega-3 PUFAs resulted in significant group x time interactions for serum
triacylglycerols (TAGs; P = 0.05); at 24 wk the control and two oily fish groups
showed lower TAG than did the white fish/sunflower group (P = 0.05). Reductions
in TAG, associated with increased oily fish intakes, were maximized when combined
with lower dietary LA:LNA. There were no significant changes in several other
cardiovascular disease risk markers. CONCLUSIONS: Two portions of oily fish per
week led to significant reductions in TAG relative to consumption of two portions
of white fish per week. Changes in TAG were maximized when combined with lower
LA:LNA.
PMID- 17027439
TI - Impact of average patient acuity on staffing of the phase I PACU.
AB - The authors consider methods for determining staffing requirements for a Phase I
PACU. Given that the total number of nursing hours per day is limited by
budgetary constraints, PACU staffing can be adjusted to minimize the percentage
of days that the PACU is full and cannot accept additional patients from the OR.
Except for very small PACUs, the number of staffing options is so large that
computer optimization methods must be used. In addition, patient acuity must be
incorporated into the staffing plan. Methods are described for adjusting staffing
requirements when some patient acuities differ from 1 nurse:2 patients, when
patients transition from one acuity to another, and when acuity is not known for
all patients.
PMID- 17027440
TI - Effectiveness of femoral nerve blockade for pain control after total knee
arthroplasty.
AB - Control of postoperative pain is a major concern for patients undergoing total
knee arthroplasty (TKA). The purpose of this study was to investigate pain
control and opioid use, as well as length of stay, ambulation time, antiemetic
use, and degree of mobilization for patients undergoing total knee arthroplasty,
comparing those receiving femoral nerve block (FNB) to those receiving no femoral
nerve block. Using retrospective patient record data, 133 subjects from an acute
care community hospital in western Canada were split into three groups: no FNB
(control group, n = 49), single-shot FNB (n = 33), and continuous FNB (n = 51).
There was a statistically significant improvement in pain control on day of
surgery for the FNB group compared with the no-FNB group, and reduction in opioid
usage on days 0, 1, and 2 in the continuous FNB group compared with the no-FNB
and single-shot group. Also noted was a statistically significant reduction in
antiemetic use in the FNB compared with the no-FNB group on the day after
surgery. This study is in accordance with earlier studies that support continuous
FNB as an effective method for achieving postoperative pain control and reducing
opioid use for patients undergoing TKA.
PMID- 17027441
TI - Surgical site verification: A through Z.
AB - Performing the correct procedure on the correct patient has always been of prime
importance to all health care providers. For the past six years, it has been a
patient safety initiative priority of the Joint Commission on Accreditation of
Healthcare Organizations (JCAHO). Before JCAHO took the lead in this arena,
however, health care facilities handled this issue with individualized policies
and procedures. This became problematic because physicians practice in multiple
institutions that could have conflicting policies, which could confuse the issue.
This case study presents the evolution of the surgical side marking and site
verification policy at St Joseph's Wayne Hospital, Wayne, NJ. It has been a
painful process, requiring numerous policy rewrites with updated information as
prescribed by JCAHO. Enforcing physician compliance and continually re-educating
nurses with each new JCAHO change proved challenging. The marking of surgical
sides and verification of all sites, however, has proven to be a collaborative
effort with safe patient outcomes as the shared goal.
PMID- 17027442
TI - Detection and treatment of perioperative corneal abrasions.
AB - Corneal abrasion is the most common ocular injury occurring in the perioperative
period. Corneal abrasion may occur during general anesthesia, monitored
anesthesia care, regional anesthesia, or in the immediate recovery period. This
injury is not usually apparent until the patient is in the PACU, and the
perianesthesia nurse may be the first clinician to detect this complication.
Preventive measures and vigilant care can help reduce the incidence of corneal
abrasion in susceptible patients. Early detection and prompt intervention may
help reduce the incidence of ocular morbidity. The purpose of this article is to
explore the incidence, mechanism of injury, prevention, recognition, and
treatment of perioperative corneal abrasion.
PMID- 17027443
TI - Outcomes measurement in ambulatory surgery.
PMID- 17027444
TI - Perianesthesia staffing...thinking beyond numbers.
PMID- 17027445
TI - What a pain!
PMID- 17027446
TI - A tragedy unfolds: lessons to learn.
PMID- 17027447
TI - Binding mode of porphyrins to poly[d(A-T)(2)] and poly[d(G-C)(2)].
AB - We examined the binding geometry of Co-meso-tetrakis (N-methyl pyridinium-4
yl)porphyrin, Co-meso-tetrakis (N-n-butyl pyridinium-4-yl)porphyrin and their
metal-free ligands to poly[d(A-T)(2)] and poly[d(G-C)(2)] by optical
spectroscopic methods including absorption, circular and linear dichroism
spectroscopy, and fluorescence energy transfer technique. Signs of an induced CD
spectrum in the Soret band depend only on the nature of the DNA sequence; all
porphyrins exhibit negative CD when bound to poly[d(G-C)(2)] and positive when
bound to poly[d(A-T)(2)]. Close analysis of the linear dichroism result reveals
that all porphyrins exhibit outside binding when complexed with poly[d(A-T)(2)],
regardless of the existence of a central metal and side chain. However, in the
case of poly[d(G-C)(2)], we observed intercalative binding mode for two
nonmetalloporphyrins and an outside binding mode for metalloporphyrins. The
nature of the outside binding modes of the porphyrins, when complexed with
poly[d(A-T)(2)] and poly[d(G-C)(2)], are quite different. We also demonstrate
that an energy transfer from the excited nucleo-bases to porphyrins can occur for
metalloporphyrins.
PMID- 17027448
TI - Anomalous phase transition in
dipalmitoylphosphatidylethanolamine/palmitoylphosphatidylcholine/water system.
AB - An anomalous phase transition with a marked rise in specific heat, the isobaric
thermal expansion coefficient, and the compressibility coefficient at 62.5
degrees C for an equimolar mixture of 1,2-dipalmitoyl-sn-glycero-3
phosphoethanolamine (DPPE) and 1-palmitoyl-sn-glycero-3-phosphocholine (PLPC), in
water (34 wt.%) has been shown by differential scanning calorimetry, scanning
dilatometry and isothermal compressibility measurements. This transition occurs
15 degrees C above a first-order transition observed in the same system. (31)P
and (2)H nuclear magnetic resonance results are consistent with the occurrence of
'defects' in the bilayer in the temperature range between the first and the
anomalous phase transitions. It is proposed that conically, PLPC molecules prefer
regions with high curvature in the defective bilayer, while DPPE molecules are
mostly confined to the flat regions of the bilayers.
PMID- 17027449
TI - Thermodynamics of the hydration of non-polar substances.
AB - We re-examine the numerical value and physical significance of T(S) the
temperature where the entropy of transfer Delta(L)(W)S from the pure hydrocarbon
liquid into water is zero. It is shown that the numerical value of T(S) depends
on the convention adopted for calculating Delta(L)(W)G from solubility data at 25
degrees C and on the Delta(L)(W)C(P) fitting function. It is concluded that the
interpretation of T(S) as the temperature where hydration ceases cannot be
sustained. As previously reported [R.L. Baldwin. N. Muller, Proc. Natl. Acad.
Sci. USA, 89 (1992) 7110], hydration must vanish at a temperature T' > T(S),
where its experimental manifestation, i.e., Delta(L)(W)C(P), is zero. We discuss
the concept of water relaxation around a non-polar solute molecule and its
relation to the hydration process.
PMID- 17027450
TI - An improved approximate solution of the Lamm equation for the simultaneous
estimation of sedimentation and diffusion coefficients from sedimentation
velocity experiments.
AB - Sedimentation and diffusion coefficients are important parameters to describe
size and shape of macromolecules in solution. The data can be obtained from
sedimentation velocity experiments by a nonlinear fitting procedure using
approximate solutions for the Lamm equation. Here, we present a modification of
such a model function that was originally proposed by Fujita [H. Fujita,
Mathematical Theory of Sedimentation Analysis, Wiley, New York, 1962]. The
extended model function is well suitable to study low molecular mass compounds.
The improvement of this solution given here is based on using an adjustable value
for the explicit integration variable, z, the reduced radius. This modification
leads to more accurate sedimentation and diffusion coefficients compared to using
a constant value of 0.5 as used by Fujita. The advantage of our modification was
demonstrated by the analysis of noise-free curves calculated using the finite
element method, as well as experimental curves obtained for the peptides
angiotensin I and II. The relatively low sedimentation and diffusion coefficients
found for both substances indicate that the peptides exist as extended chains of
about 3.65 nm (angiotensin I) or 3.04 nm length (angiotensin II) in solution. The
lack of higher-order structure of the peptides that was derived also from CD
spectra might facilitate receptor binding, and could be one reason for the fast
proteolytic digestion of the free peptides.
PMID- 17027451
TI - Photophysics of ethidium bromide complexed to ct-DNA: a maximum entropy study.
AB - Time-integrated and time-resolved fluorescence spectroscopies have been used to
probe the photophysical properties of ethidium bromide (Eb) complexed to calf
thymus DNA (ct-DNA). Fluorescence decay profiles are obtained using the technique
of time-correlated single photon counting (TCSPC), and subsequently analysed
using conventional sum-of-exponential (SOE) routines and also the maximum entropy
method (MEM). Through use of these methods and simulated decay data, it is
demonstrated that the kinetics of Eb in the presence of ds-DNA are best described
by a generic model consisting of three exponential terms. At all DNA:Eb ratios
and NaCl concentrations studied, free Eb is detected. Furthermore, Eb is found to
interact with ds-DNA through two mechanisms, each distinguishable by its
fluorescence decay time. Eb is shown to interact with DNA through classic
intercalation, and also through binding at secondary sites. The component decay
times are shown to be a function of NaCl concentration but independent of DNA:Eb
molar ratio.
PMID- 17027452
TI - Dynamic properties of individual water molecules in a hydrophobic pore lined with
acyl chains: a molecular dynamics study.
AB - Recently, a certain class of synthetic molecules has been shown to form ion
channels, the pore of which is lined with hydrophobic acyl chains [M. Sokabe, in:
F. Oosawa, H. Hayashi, T. Yoshioka (Eds.), Transmembrane Signaling and Sensation,
JSSP/VNU Science Press BV, Tokyo, 1984, p. 119; F. Hayashi, M. Sokabe, M. Takagi,
K. Hayashi, U. Kishimoto, Biochim. Biophys. Acta, 510 (1978) 305; M.J. Pregel, L.
Jullien, J. Canceill, L. Lacombe, J.M. Lehn, J. Chem. Soc. Perkin Trans., 2
(1995) 417; Y. Tanaka, Y. Kobuke, M. Sokabe, Angew. Chem. Int. Ed. Engl., 34
(1995) 693; M. Sokabe, Z. Qi, K. Donowaki, H. Ishida, K. Okubo, Biophys. J., 70
(1996) A201; H. Ishida, K. Donowaki, Y. Inoue, Z. Qi, M. Sokabe, Chem. Lett.
(1997) p. 953]. As an initial step towards understanding the physical mechanisms
of ion permeation across such a hydrophobic pore, systematic molecular dynamics
simulations were performed to investigate dynamic and energetic properties of
water molecules inside the pore using a dimer of alanine-N'-acylated cyclic
peptide as a channel model. Dynamic energy profiles for water molecules indicated
that the energy barrier at the middle region of the pore is approximately 2-3
kcal/mol higher than that in the cap water region which was defined as a vicinity
region of the channel entrance. Energetics analyses demonstrated that the mutual
interactions among intrapore water molecules are the major factor to give
favorable interaction (negative energy contribution) for themselves. The pore,
despite being lined with acyl chains, has a favorable van der Waals interaction
with intrapore water molecules. These results may help to explain why water
filled channels can be formed by the hydrophobic helices in natural channels.
PMID- 17027453
TI - Enzymatic reactions in small spatial volumes: comment on a model of Hess and
Mikhailov.
AB - Recently Hess and Mikhailov pointed out that in small subcellular compartments
diffusion is so fast that mixing is instantaneous on the time scale of many
enzymatic reactions. This opens the possibility for synchronizing individual
reaction events. To illustrate this fact they discuss as example an irreversible
enzymatic reaction with allosteric product activation. Under appropriate
conditions their model shows coherent spiking in the number of product molecules,
caused by the strong correlation between reaction events. In this model only
substrate binding is an indeterministic process, all other subsequent transitions
between different enzyme states being deterministic, contrary to real processes.
The purpose of the present paper was to investigate this interesting phenomenon
by means of a more realistic modification of the original model, with only
probabilistic transitions. In an attempt to obtain spiking, which was not
observed under these conditions, the model was extended to make a clear
distinction between allosteric high and low affinity substrate binding, in
contrast to the original model using a product dependent mean binding
probability. However no periodic signal was detectable in the indeterministic
version of the Hess Mikhailov model or the extended version, either by means of
direct visualization or on autocorrelation or Fourier analysis. Reasons why
spiking is not observed in indeterministic enzyme models are discussed.
PMID- 17027455
TI - Sterically stabilized liposomes of DPPC/DPPE-PEG:2000. A spin label ESR and
spectrophotometric study.
AB - The chain dynamics and the thermotropic phase behavior of sterically stabilized
liposomes obtained introducing in the host bilayer matrix of DPPC up to 7 mol% of
the polymer-lipid DPPE-PEG:2000 were investigated by spin label electron spin
resonance spectroscopy and spectrophotometry. The experimental data indicate that
the dispersions have the dynamic and thermotropic characteristics of normal
lamellar phase. Moreover, using spin labels that locate both in the interfacial
and in the hydrocarbon regions, namely TEMPO-stearate, 5- and 16-PCSL, we find
that relative to the unmodified DPPC bilayers, the polymer-grafted bilayers are
loosely packed in the interfacial region and have reduced chain mobility in the
gel phase. From the temperature dependence of the partition coefficient (P(c)),
of the spin probe DTBN between the aqueous and the fluid hydrophobic regions of
the bilayers and from the melting curves of the absorbance at 400 nm, we observe
a slight influence on the endothermic phase transitions when increasing the
concentration of the polymer-lipid in the DPPC bilayers, the influence being more
evident in the pre-transition.
PMID- 17027456
TI - Plant sterols: a neutron diffraction study of sitosterol and stigmasterol in
soybean phosphatidylcholine membranes.
AB - Neutron scattering experiments have been performed on oriented Soybean
phosphatidylcholine (SPC) bilayers, containing sitosterol or stigmasterol, two
major sterols of plant plasma membranes. Sitosterol and stigmasterol were either
protonated or deuterated on position C25 of the lateral chain. Incorporation of
sitosterol leads to an increase of the hydrophobic thickness of SPC bilayers of
1.2 and 2 A when present, at 16 and 30 mol%, respectively. On the other hand, no
change was observed when stigmasterol is present in the bilayer at its maximal
solubility of 16 mol%. These results are in agreement with the fact that
sitosterol is more efficient than stigmasterol to order acyl chains of SPC, as
already shown with other biophysical techniques. In order to get more insight
into the behavior of the lateral chains of the two sterols, the proton-deuterium
contrast method was used in order to locate the (2)H25 atoms of the two sterols.
For sitosterol, this atom was found close to the center of the bilayer at +/
(1.6+/-0.2 A), with a width, nu=2.5+/-0.5 A. For stigmasterol, the difference
profile could be fitted in two different ways: either two possible locations are
found at +/-(2.3+/-0.2 A) and +/-(10+/-0.2 A) with the same width, nu=2.5+/-0.5 A
or only one broad distribution at +/-(6.1+/-0.3 A), nu=8.5+/-0.7 A. The results
are discussed in terms of difference of dynamics for the lateral chain of the two
sterols.
PMID- 17027457
TI - Hydration of diglycyl tripeptides with non-polar side chains: a volumetric study.
AB - We have determined the apparent molar volumes and the apparent molar adiabatic
compressibilities at 25 degrees C of 10 X-Gly-Gly and Gly-Gly-X tripeptides in
which X represents a residue with a non-polar side chain. We also have determined
the changes in volume and compressibility which accompany neutralization of the
amino and carboxyl termini in these tripeptides. The mutual influence of the non
polar side chain of the X residue and the terminal amino and carboxyl groups on
the hydration of each other depends on the chemical nature of the side chain and
the state of ionization of the termini. We interpret our data in terms of the
hydration of the component aliphatic, aromatic, and charged atomic groups, as
well as the mutual interactions between these groups.
PMID- 17027458
TI - Mean-field analysis of protein-protein interactions.
AB - Calculations were performed on the D1.3-E5.2 antibody-antibody complex estimating
the binding affinities of the wild-type and 16 alanine substitutions. Analyzed
were structural models of the interfacial region containing a zinc ion and
crystallographic waters. A continuum approach was used to evaluate the
electrostatic free energies and the hydrophobic effect was calculated by
employing a buried molecular surface area relationship. Estimates of the absolute
binding affinity reproduced the experimental value within the uncertainty of
assessing entropic and strain energy contributions. The best correlation for
mutants with experimental data was achieved when the hydrophilicity of created
cavities were considered, and yielded a correlation coefficient of 0.7 and an
average error of +/-1.4 kcal/mol. Empirically fitting the free energy function
produced a smaller error of +/-1.0 kcal/mol. Depending on the electrical
potential and electrostatic reorganization, scaling the 'protein dielectric
constant' to approximately 10 may improve the accuracy of continuum models for
evaluating amino acid substitutions.
PMID- 17027460
TI - Kinetic asymmetry as a key source of functional diversity in biochemical
networks.
AB - From the analysis of the dynamic properties of various symmetric and asymmetric
kinetic schemes, the present report demonstrates that all kinetic schemes, which
can be hypothetically divided into two equal halves about an axis of mirror
symmetry, are endowed with structural metastability under mass-closed conditions.
In mass-closed symmetric schemes, absolute symmetry in reaction conditions in two
halves is essential for the occurrence of ordered dynamic behaviour. Even an
infinitesimal deviation from the symmetry relations instantaneously drives such
systems from limit-cycles to turbulence. Reaction schemes with no axes of
symmetry may exhibit a large variety of complex, structurally stable temporal
order for wide ranges of values of system parameters and variables. Kinetic
asymmetry, therefore, may confer to biochemical networks the functional diversity
as well as stability against environmental perturbations.
PMID- 17027461
TI - Effect of cation and anion of an electrolyte on apparent molar volume, isentropic
compressibility and refractive index of glycine in aqueous solutions.
AB - Experiments at 298.15 K have been performed to measure the density, velocity of
sound and refractive index in three water+glycine+electrolyte systems. The
electrolytes studied were KCl, KNO3 and NaNO3. The values of apparent molar
volume and isentropic compressibility of glycine in aqueous electrolyte solutions
were calculated from the measured data. The results obtained in this study and
those reported previously for water+glycine+NaCl system have been comparatively
studied. The results show that the nature of both the cation and the anion of an
electrolyte influence the behaviour of glycine in aqueous solutions. For all four
electrolytes studied, the comparison shows a positive volume transfer for glycine
from an electrolyte solution to a more concentrated solution of the same
electrolyte. The results also show a negative apparent isentropic compressibility
for glycine in the presence of the electrolytes studied. These effects indicate
that the volume of a glycine molecule is larger in solutions with higher
electrolyte concentration and the water molecules around the glycine molecules
are less compressible than the water molecules in the bulk solution. These
effects were attributed to the doubly charged behaviour of glycine and to the
formation of physically bonded ion-pairs between the charged groups of glycine
and the cation and the anion of the electrolyte.
PMID- 17027462
TI - High pressure fourier transform infrared spectroscopy of poly(dA)poly(dT),
poly(dA) and poly(dT).
AB - The effect of hydrostatic pressure upon the DNA duplex, poly(dA)poly(dT), and its
component single strands, poly(dA) and poly(dT) has been studied by fourier
transform infrared spectroscopy (FT-IR). The spectral data indicate that at 28
degrees C and pressures up to 12 kbar (1200 MPa) all three polymers retain the B
conformation. Pressure causes the band at 967 cm(-1), arising from water
deoxyribose interactions, to shift to higher frequencies, a result consistent
with increased hydration at elevated pressures. A larger pressure-induced
frequency shift in this band is observed in the single stranded polymers than in
the double stranded molecule, suggesting that the effect of pressure on the
hydration of single strands may be greater than upon a double stranded complex. A
pressure-dependent hypochromicity in the bands attributed to base stacking
indicates that pressure facilitates the base stacking in the three polymers, in
agreement with previous assessments of the importance of stacking in the
stabilization of DNA secondary structure at ambient and high pressures.
PMID- 17027463
TI - Folding and unfolding of a giant duplex-DNA in a mixed solution with polycations,
polyanions and crowding neutral polymers.
AB - To understand the conformational behavior of a giant duplex-DNA chain in a mixed
solution with various biopolymers with different state of ionization, the higher
order structure of the DNA chain was analyzed with a fluorescence microscope in
the presence of polycations (poly-arginine), polyanions (poly-glutamic acid), and
neutral polymers (poly-ethylene glycol) as a model for cellular environment.
Concentrated medium with neutral polymer induced the discrete folding transition
of the DNA. At the threshold condition for the transition, addition of small
amounts of either the polycation or the polyanion caused marked structural
changes in the folded DNAs. Based on thermodynamic considerations on the
experimental results, profile of free energy of a single giant DNA chain was
depicted with respect to the size, or the expansion factor alpha, in the three
dimensional structure of the DNA. The effect of the neural crowding polymer on
the degree of folding of a single giant DNA chain is discussed in a semi
quantitative manner.
PMID- 17027464
TI - Effect of transport and competition on ligand binding.
AB - We present a model to describe the physics of chemoreception in processes
determined by competitive ligand binding. Our model describes the competition
between various populations, such as ligands vs. blockers and receptors vs.
decoys, in protein activation when diffusion is rate-determining. Full spatio
temporal solutions can be obtained numerically. The model structure is kept
simple enough as to permit its easy generalization to describe a large subset of
the manifold of possible situations occurring in nature. The power and simplicity
of the proposed method are exhibited through the solution of several examples
which are discussed in detail.
PMID- 17027465
TI - Conversions of the left-handed form and the protonated form of DNA back to the
bound right-handed form by sanguinarine and ethidium: a comparative study.
AB - The interaction of sanguinarine and ethidium with right-handed (B-form), left
handed (Z-form) and left-handed protonated (designated as H(L)-form) structures
of poly(dG-dC).poly(dG-dC) and poly(dG-me5dC).poly(dG-me5dC) was investigated by
measuring the circular dichroism and UV absorption spectral analysis. Both
sanguinarine and ethidium bind strongly to the B-form DNA and convert the Z-form
and the H(L)-form back to the bound right-handed form. Circular dichroic data
also show that the conformation at the binding site is right-handed, even though
adjacent regions of the polymer have a left-handed conformation either in Z-form
or in H(L)-form. Both the rate and extent of B-form to Z-form transition were
decreased by sanguinarine and ethidium under ionic conditions that otherwise
favour the left-handed conformation of the polynucleotides. The rate of decrease
is faster in the case of ethidium as compared to that of sanguinarine. Scatchard
analysis of the spectrophotometric data shows that sanguinarine binds strongly to
both the polynucleotides in a non-cooperative manner under B-form conditions, in
sharp contrast to the highly-cooperative binding under Z-form and H(L)-form
conditions. Correlation of binding isotherms with circular dichroism data
indicates that the cooperative binding of sanguinarine under the Z-form and the
H(L)-form conditions is associated with a sequential conversion of the polymer
from a left-handed to a bound right-handed conformation. Determination of bound
alkaloid concentration by spectroscopic titration technique and the measurement
of circular dichroic spectra have enabled us to calculate the number of base
pairs of Z-form and H(L)-form that adopt a right-handed conformation for each
bound alkaloid. Analysis reveals that 2-3 base pairs (bp) of Z-form of poly(dG
dC).poly(dG-dC) and poly(dG-me5dC).poly(dG-me5dC) switch to the right-handed form
for each bound sanguinarine, while approximately same number of base pairs switch
to the bound right-handed form in complexes with H(L)-form of these
polynucleotides. Comparative binding analysis shows that ethidium also converts
approximately 2 bp of Z-form or H(L)-form to bound right-handed form under same
experimental conditions. Since sanguinarine binds preferentially to alternating
GC sequences, which are capable of undergoing the B to Z or B to H(L) transition,
these effects may be an important part in understanding its extensive biological
activities.
PMID- 17027466
TI - Protein heat capacity: inconsistencies in the current view of cold denaturation.
AB - The present study shows on the basis of the thermodynamic stability criterion
(partial differential S/partial differential T)p>0 that partitioning of the
entropy of cold-unfolding of a protein into independent positive conformational
and negative hydrational contributions is incorrect. Furthermore it provides a
new microscopic interpretation of protein heat capacity that takes into account
the significant fluctuations in energy and entropy which result from the small
size of these macromolecules.
PMID- 17027467
TI - Effects of solvent perturbation on gelation driven by spinodal demixing.
AB - We study effects of solvent perturbation on kinetic competition between spinodal
demixing and gelation in agarose solutions at a concentration of 5 g/l. Two
different cosolutes (tert-butyl alcohol and trimethyl amine N-oxide) known for
altering in opposite way solvent-mediated interactions are chosen. By rheometry,
static and dynamic light scattering experiments, we show that the cosolute
presence shifts the boundary of the instability region of solution leaving
unaffected temperature and polymer concentration values required for percolation.
Results suggest that an appropriate choice of quenching temperature and solvent
allows controlling the gelation time and the gel structural properties.
PMID- 17027468
TI - Effects of diacylglycerol on the structure and phase behaviour of non-bilayer
forming phospholipid.
AB - The phase behaviour of mixed aqueous dispersions of the monomethyl derivative of
dioleoylphosphatidylethanolamine and dipalmitoylglycerol has been characterised
by X-ray diffraction, differential scanning calorimetry and freeze-fracture
electron microscopy for mixtures containing dipalmitoylglycerol in the
concentration range 0-20 mol%. Dispersions prepared at temperatures where the
phospholipid exhibits a liquid-crystalline lamellar phase show that
dipalmitoylglycerol is completely phase separated into aggregates of stable
crystal phase (beta'-phase). Heating mixed dispersions results in transformation
of lamellar into hexagonal-II structure commencing at approximately 45 degrees C.
This temperature coincides with a disappearance of beta'-phase of DPG which
becomes incorporated into hexagonal-II phase. The pure phospholipid is
transformed upon cooling from hexagonal-II into characteristic cubic phases; the
formation of cubic phase is prevented by the presence of dipalmitoylglycerol and
mixed dispersions initially form a lamellar liquid-crystalline phase in which the
lipids are phase separated. The X-ray and thermal data suggest that relatively
small domains of metastable crystal phase (alpha-phase) of DPG form initially on
cooling and these subsequently coalesce and transform to beta'-phase.
PMID- 17027469
TI - Thermodynamic and spectroscopic features of the behavior of amphotericin B in
aqueous medium.
AB - The interaction between amphotericin B molecules in aqueous medium solution was
studied using absorption and circular dichroism approaches. The results showed
that at concentrations below 1 microM of amphotericin B, an equilibrium between
the monomer and aggregate occurred with a constant of approximately 0.6x10(6) M(
1). The aggregate formation constant was dependent on the experimental conditions
of the medium: its value increased at acidic pH values, while alkaline medium
induced the equilibrium displacement to the monomer formation. Either neutral
salts or chaotropic agents such as urea prevented the formation of the aggregate.
The presence of net electrical charge on the amine and carboxyl groups plays a
role in the thermodynamic stability of the aggregate. A hydrophobic effect was
also found between the monomer form and the water molecules of neighbours. In the
aggregate formation water molecules were released contributing to an increase in
the entropic change.
PMID- 17027470
TI - Lattice simulations of protein crystal formation.
AB - A new algorithm is presented for the lattice simulation of protein crystal
growth. The algorithm allows the calculation of the size distribution of
microcrystals in the volume and timescale of experiments and within the framework
of the previously-published microscopic model [A.M. Kierzek, W.M. Wolf, P.
Zielenkiewicz, Biophys. J. 73 (1997) 571-580]. Simulations for the tetragonal
lysozyme crystal show that there are two critical sizes in the development of
ordered phase. The first one corresponds to the size of the smallest stable
complex which, in the case of the tetragonal lysozyme crystal, is the particular
tetramer. In a volume of 5 mul the tetramer appears in the millisecond timescale.
The second critical radius of approximately 100 monomers is only reached by a few
of all the smallest stable complexes formed in the solution. The model predicts
that out of 10(7) tetramers which appear in solution, only eight reach the size
of 100 monomers within 8 h. After exceeding the second critical radius the
microcrystals grow to the size of 10(4) monomers in the minute timescale and are
thus assumed to quickly lead to macroscopic crystals. The predicted number of
crystals formed during 8 h of nucleation is in qualitative agreement with
arrested nucleation experiments.
PMID- 17027471
TI - Evolutionary contingency.
PMID- 17027472
TI - Evolutionary convergence.
PMID- 17027473
TI - Form and function in systems neuroscience.
AB - 'Form follows function' is an architectural philosophy attributed to the great
American architect Louis Sullivan, and later taken up by the Bauhaus movement. It
stresses that the form of a building should reflect its function. Neuroscientists
have used the converse of this dictum to learn the functions of neural circuits,
believing that if we study neural architecture, it will lead us to an
understanding of how neural systems function. New tools for studying the
structure of neural circuits are being developed, so it is important to discuss
what the old techniques have taught us about how to derive function from the form
of a neural circuit.
PMID- 17027474
TI - Evolvability.
PMID- 17027475
TI - Neural basis of time changes during saccades.
PMID- 17027476
TI - Archerfish shots are evolutionarily matched to prey adhesion.
PMID- 17027477
TI - DNA topology: dynamic DNA looping.
AB - The DNA in repressive loops is often tightly bent. DNA flexibility imposes
significant constraints on their topology suggesting that they may exist as
perturbations in plectonemic DNA.
PMID- 17027478
TI - Growth control: p53, the guardian angel of compensatory proliferation.
AB - Compensatory growth, or regeneration, is used to replace damaged tissue during
animal development. Recent work has revealed a new role for Drosophila p53 in the
compensatory proliferation of cells that are needed to repair damaged tissues, a
role that requires the non-apoptotic function of the caspase protease Dronc.
PMID- 17027479
TI - Nursing behavior: remembrance of things past.
AB - Successful suckling is vital to the survival of mammalian newborns. In many
mammals, nursing behavior is triggered by maternally derived odors. Such odors
may also promote the learned association of odorant cues present in the
environment during nursing.
PMID- 17027480
TI - Replicative helicases: a staircase with a twist.
AB - The first crystal structure of a ring helicase encircling single-stranded DNA
reveals a mechanism for ATP-dependent DNA translocation.
PMID- 17027481
TI - Perception: transient disruptions to neural space-time.
AB - How vision operates efficiently in the face of continuous shifts of gaze remains
poorly understood. Recent studies show that saccades cause dramatic, but
transient, changes in the spatial and also temporal tuning of cells in many
visual areas, which may underly the perceptual compression of space and time, and
serve to counteract the effects of the saccades and maintain visual stability.
PMID- 17027482
TI - Transcription: adjusting to adversity by regulating RNA polymerase.
AB - Under growth-limiting conditions, budding yeast shut down transcription of genes
of the translation apparatus. Recent studies have shown that this response is
signaled, in part, by multiple pathways that converge on Maf1, leading to a
change of this protein's phosphorylation state and its relocation to the nucleus,
where it represses RNA polymerase III.
PMID- 17027483
TI - Animal cognition: an insect's sense of time?
AB - For Immanuel Kant, time was the very form of the inner sense, the bedrock of our
consciousness and also the origin of arithmetic ability. New research on
bumblebees has shown that even an invertebrate with a brain the size of a pinhead
can actively sense the passage of elapsed time, allowing it to predict when
certain salient events will occur in the future.
PMID- 17027484
TI - G-protein signaling: a new branch in an old pathway.
AB - A recent study provides evidence for a new branch of the yeast mating pathway in
which a G-protein alpha subunit directly activates phosphatidylinositol 3-kinase
at endosomes.
PMID- 17027485
TI - A novel Eph receptor-interacting IgSF protein provides C. elegans motoneurons
with midline guidepost function.
AB - BACKGROUND: The ventral midline is a prominent structure in vertebrate and
invertebrate nervous systems that provides crucial topological information for
guiding axons to their appropriate target destinations. Rather than being
composed of specialized midline glia cells as in many other species, the
embryonic midline of the nematode Caenorhabditis elegans is physically defined by
motoneuron cell bodies that separate the left from the right ventral cord
fascicles. Their function during development, if any, is not known. RESULTS: We
show here that besides being components of the postembryonic locomotory circuit,
these embryonic motoneurons (eMNs) actively provide midline guidance information
for a specific subset of ventral midline axons. This information is provided in
the form of a novel, cell-surface-anchored immunoglobulin superfamily (IgSF)
member, WRK-1. WRK-1 acts in eMNs to prevent follower axons from inappropriately
crossing the ventral midline. We describe the function of the Eph receptor vab-1
and multiple ephrin ligands at the midline, and we show by double mutant analysis
and physical interaction tests that WRK-1 functionally interacts with the Eph
receptor system. This interaction appears to occur exclusively in the context of
axon guidance at the ventral midline but not in other cellular contexts, thereby
suggesting that Eph receptor signaling is mechanistically distinct in different
tissue types. CONCLUSIONS: Our studies reveal cellular and molecular components
of axon midline patterning and suggest that Ephrin signaling relies on previously
unknown accessory components.
PMID- 17027486
TI - Seeing or doing? Influence of visual and motor familiarity in action observation.
AB - The human brain contains specialized circuits for observing and understanding
actions. Previous studies have not distinguished whether this "mirror system"
uses specialized motor representations or general processes of visual inference
and knowledge to understand observed actions. We report the first neuroimaging
study to distinguish between these alternatives. Purely motoric influences on
perception have been shown behaviorally, but their neural bases are unknown. We
used fMRI to reveal the neural bases of motor influences on action observation.
We controlled for visual and knowledge effects by studying expert dancers. Some
ballet moves are performed by only one gender. However, male and female dancers
train together and have equal visual familiarity with all moves. Male and female
dancers viewed videos of gender-specific male and female ballet moves. We found
greater premotor, parietal, and cerebellar activity when dancers viewed moves
from their own motor repertoire, compared to opposite-gender moves that they
frequently saw but did not perform. Our results show that mirror circuits have a
purely motor response over and above visual representations of action. We
understand actions not only by visual recognition, but also motorically. In
addition, we confirm that the cerebellum is part of the action observation
network.
PMID- 17027487
TI - Distinct developmental mechanisms reflect the independent origins of leaves in
vascular plants.
AB - Vascular plants diverged more than 400 million years ago into two lineages, the
lycophytes and the euphyllophytes . Leaf-like organs evolved independently in
these two groups . Microphylls in lycophytes are hypothesized to have originated
as lateral outgrowths of tissue that later became vascularized (the enation
theory) or through the sterilization of sporangia (the sterilization hypothesis)
. Megaphylls in euphyllophytes are thought to represent modified lateral branches
. The fossil record also indicates that the seed plant megaphyll evolved uniquely
in the ancestor of seed plants, independent of megaphylls in ferns, because seed
plants evolved from leafless progymnosperm ancestors . Surprisingly, a recent
study of KNOX and ARP gene expression in a lycophyte was reported to indicate
recruitment of a similar mechanism for determinacy in both types of leaves . We
examined the expression of Class III HD-Zip genes in the lycophyte Selaginella
kraussiana and in two gymnosperms, Ginkgo and Pseudotsuga. Our data indicate that
mechanisms promoting leaf initiation, vascularization, and polarity are quite
different in lycophytes and seed plants, consistent with the hypotheses that
megaphylls originated as lateral branches whereas microphylls originated as
tissue outgrowths.
PMID- 17027488
TI - Somatosensory precision in speech production.
AB - Speech production is dependent on both auditory and somatosensory feedback.
Although audition may appear to be the dominant sensory modality in speech
production, somatosensory information plays a role that extends from brainstem
responses to cortical control. Accordingly, the motor commands that underlie
speech movements may have somatosensory as well as auditory goals. Here we
provide evidence that, independent of the acoustics, somatosensory information is
central to achieving the precision requirements of speech movements. We were able
to dissociate auditory and somatosensory feedback by using a robotic device that
altered the jaw's motion path, and hence proprioception, without affecting speech
acoustics. The loads were designed to target either the consonant- or vowel
related portion of an utterance because these are the major sound categories in
speech. We found that, even in the absence of any effect on the acoustics, with
learning subjects corrected to an equal extent for both kinds of loads. This
finding suggests that there are comparable somatosensory precision requirements
for both kinds of speech sounds. We provide experimental evidence that the neural
control of stiffness or impedance--the resistance to displacement--provides for
somatosensory precision in speech production.
PMID- 17027489
TI - A novel mechanism for the formation of actin-filament bundles by a nonprocessive
formin.
AB - Actin-filament bundles (or cables) have a structural role during cell division
and morphogenesis, but also serve as important "tracks" for the transport of
materials during cytokinesis and polarized cell growth. However, the dynamic
formation of these longitudinal actin-filament higher-order structures is not
understood. Recently, several lines of evidence suggest that formins provide one
avenue for the initiation of actin cables in vivo. A popular model for the
mechanism of polymerization of actin filaments by formin involves the processive
movement of formin attached at the barbed end of an elongating filament. In the
present study, we use an in vitro system to reconstitute the dynamic formation of
actin-filament bundles generated by Arabidopsis FORMIN1 (AFH1). To be able to
visualize individual events in such a complex system, we used real-time
evanescent-wave microscopy. Surprisingly, we find that AFH1 is a nonprocessive
formin that moves from the barbed end to the side of an actin filament after the
nucleation event. We show why this new mechanism of nucleation by a member of the
formin family is important for bundle formation. Finally, we analyze the
different parameters controlling the dynamic formation of such longitudinal actin
filament bundles.
PMID- 17027490
TI - Generation of specific Ca(2+) signals from Ca(2+) stores and endocytosis by
differential coupling to messengers.
AB - It remains unclear how different intracellular stores could interact and be
recruited by Ca(2+)-releasing messengers to generate agonist-specific Ca(2+)
signatures. In addition, refilling of acidic stores such as lysosomes and
secretory granules occurs through endocytosis, but this has never been
investigated with regard to specific Ca(2+) signatures. In pancreatic acinar
cells, acetylcholine (ACh), cholecystokinin (CCK), and the messengers cyclic ADP
ribose (cADPR), nicotinic acid adenine dinucleotide phosphate (NAADP), and
inositol 1,4,5-trisphosphate (IP(3)) evoke repetitive local Ca(2+) spikes in the
apical pole. Our work reveals that local Ca(2+) spikes evoked by different
agonists all require interaction of acid Ca(2+) stores and the endoplasmic
reticulum (ER), but in different proportions. CCK and ACh recruit Ca(2+) from
lysosomes and from zymogen granules through different mechanisms; CCK uses NAADP
and cADPR, respectively, and ACh uses Ca(2+) and IP(3), respectively. Here, we
provide pharmacological evidence demonstrating that endocytosis is crucial for
the generation of repetitive local Ca(2+) spikes evoked by the agonists and by
NAADP and IP(3). We find that cADPR-evoked repetitive local Ca(2+) spikes are
particularly dependent on the ER. We propose that multiple Ca(2+)-releasing
messengers determine specific agonist-elicited Ca(2+) signatures by controlling
the balance among different acidic Ca(2+) stores, endocytosis, and the ER.
PMID- 17027491
TI - Microtubule-associated AIR9 recognizes the cortical division site at preprophase
and cell-plate insertion.
AB - In plants, the preprophase band (PPB) of microtubules marks the cortical site
where the cross-wall will fuse with the parental wall during cytokinesis . This
band disappears before metaphase, and it is not known how the division plane is
"memorized". One idea is that the PPB leaves behind molecules involved in the
maturation of the cell plate . Here, we report on the proteomic isolation of a
novel 187 kDa microtubule-associated protein, AIR9, conserved in land plants and
trypanosomatid parasites. AIR9 decorates cortical microtubules and the PPB but is
downregulated during mitosis. AIR9 reappears at the former PPB site precisely
when the cortex is contacted by the outwardly growing cytokinetic apparatus. AIR9
then moves inward on the new cross-wall and thus forms a torus. Truncation
studies show that formation of the torus requires a repeated domain separate from
AIR9's microtubule binding site. Cell plates induced to insert outside the
predicted division site do not elicit an AIR9 torus, suggesting that AIR9
recognizes a component of the former PPB. Such misplaced walls remain immature,
based on their prolonged staining for the cell-plate polymer callose. We propose
that AIR9 may be part of the mechanism ensuring the maturation of those cell
plates successfully contacting the "programmed" cortical division site.
PMID- 17027492
TI - Katanin disrupts the microtubule lattice and increases polymer number in C.
elegans meiosis.
AB - Katanin is a heterodimer that exhibits ATP-dependent microtubule-severing
activity in vitro. In Xenopus egg extracts, katanin activity correlates with the
addition of cyclin B/cdc2, suggesting a role for microtubule severing in the
disassembly of long interphase microtubules as the cell prepares for mitosis.
However, studies from plant cells, cultured neurons, and nematode embryos suggest
that katanin could be required for the organization or postnucleation processing
of microtubules, rather than the dissolution of microtubule structures. Here we
reexamine katanin's role by studying acentrosomal female meiotic spindles in C.
elegans embryos. In mutant embryos lacking katanin, microtubules form around
meiotic chromatin but do not organize into bipolar spindles. By using electron
tomography, we found that katanin converts long microtubule polymers into shorter
microtubule fragments near meiotic chromatin. We further show that turning on
katanin during mitosis also creates a large pool of short microtubules near the
centrosome. Furthermore, the identification of katanin-dependent microtubule
lattice defects supports a mechanism involving an initial perforation of the
protofilament wall. Taken together, our data suggest that katanin is used during
meiotic spindle assembly to increase polymer number from a relatively inefficient
chromatin-based microtubule nucleation pathway.
PMID- 17027493
TI - A pheromone that rapidly promotes learning in the newborn.
AB - Mammalian neonates depend on their mother's food supply and use a defined
sequence of actions to find her mammary area. Their behavior is initially
uncertain and demanding but rapidly becomes optimal. Efficient learning is thus
operating in newborns. For instance, European rabbit (Oryctolagus cuniculus) pups
localize the nipples through typical orocephalic movements. These movements are
released by the mammary pheromone secreted in milk or by prenatally learned odor
cues. During daily nursing, they also learn odors associated with the mother,
supposedly with sucking as the main reinforcer. We here investigate the role of
the mammary pheromone as an enforcer of early olfactory learning in newborn
rabbits. In testing more than 950 pups, we show that the mammary pheromone
promotes learning of neutral odorants paired with the pheromone in single and
short trials. The pheromone-induced learning is efficient from birth and supports
successive acquisition of distinct odorants. This reveals that a mammalian
pheromone can function as a "cognitive organizer" that promotes early learning of
relevant environmental cues.
PMID- 17027494
TI - Mitosis-specific mechanosensing and contractile-protein redistribution control
cell shape.
AB - Because cell-division failure is deleterious, promoting tumorigenesis in mammals,
cells utilize numerous mechanisms to control their cell-cycle progression. Though
cell division is considered a well-ordered sequence of biochemical events,
cytokinesis, an inherently mechanical process, must also be mechanically
controlled to ensure that two equivalent daughter cells are produced with high
fidelity. Given that cells respond to their mechanical environment, we
hypothesized that cells utilize mechanosensing and mechanical feedback to sense
and correct shape asymmetries during cytokinesis. Because the mitotic spindle and
myosin II are vital to cell division, we explored their roles in responding to
shape perturbations during cell division. We demonstrate that the contractile
proteins myosin II and cortexillin I redistribute in response to intrinsic and
externally induced shape asymmetries. In early cytokinesis, mechanical load
overrides spindle cues and slows cytokinesis progression while contractile
proteins accumulate and correct shape asymmetries. In late cytokinesis,
mechanical perturbation also directs contractile proteins but without apparently
disrupting cytokinesis. Significantly, this response only occurs during anaphase
through cytokinesis, does not require microtubules, and is independent of spindle
orientation, but is dependent on myosin II. Our data provide evidence for a
mechanosensory system that directs contractile proteins to regulate cell shape
during mitosis.
PMID- 17027495
TI - Metaphase arrest by cyclin E-Cdk2 requires the spindle-checkpoint kinase Mps1.
AB - Cytostatic factor (CSF) arrests vertebrate eggs in metaphase of meiosis II
through several pathways that inhibit activation of the anaphase-promoting
complex/cyclosome (APC/C). In Xenopus, the Mos-MEK1-MAPK-p90(Rsk) cascade
utilizes spindle-assembly-checkpoint components to effect metaphase arrest.
Another pathway involves cyclin E-Cdk2, and sustained cyclin E-Cdk2 activity in
egg extracts causes metaphase arrest in the absence of Mos; this latter finding
suggests that an independent pathway contributes to CSF arrest. Here, we
demonstrate that metaphase arrest with cyclin E-Cdk2, but not with Mos, requires
the spindle-checkpoint kinase monopolar spindles 1 (Mps1), a cyclin E-Cdk2 target
that is also implicated in centrosome duplication. xMps1 is synthesized and
activated during oocyte maturation and inactivated upon CSF release. In egg
extracts, CSF release by calcium was inhibited by constitutively active cyclin E
Cdk2 and delayed by wild-type xMps1. Ablation of cyclin E by antisense
oligonucleotides blocked accumulation of xMps1, suggesting that cyclin E-Cdk2
controls Mps1 levels. During meiosis II, activated cyclin E-Cdk2 significantly
inhibited the APC/C even in the absence of the Mos-MAPK pathway, but this
inhibition was not sufficient to suppress S phase between meiosis I and II. These
results uniquely place xMps1 downstream of cyclin E-Cdk2 in mediating a pathway
of APC/C inhibition and metaphase arrest.
PMID- 17027496
TI - DNA kinks available...if needed.
PMID- 17027497
TI - The Role of histidine residues in low-pH-mediated viral membrane fusion.
AB - A central event in the invasion of a host cell by an enveloped virus is the
fusion of viral and cell membranes. For many viruses, membrane fusion is driven
by specific viral surface proteins that undergo large-scale conformational
rearrangements, triggered by exposure to low pH in the endosome upon
internalization. Here, we present evidence suggesting that in both class I
(helical hairpin proteins) and class II (beta-structure-rich proteins) pH
dependent fusion proteins the protonation of specific histidine residues triggers
fusion via an analogous molecular mechanism. These histidines are located in the
vicinity of positively charged residues in the prefusion conformation, and they
subsequently form salt bridges with negatively charged residues in the postfusion
conformation. The molecular surfaces involved in the corresponding structural
rearrangements leading to fusion are highly conserved and thus might provide a
suitable common target for the design of antivirals, which could be active
against a diverse range of pathogenic viruses.
PMID- 17027498
TI - Common evolutionary origin of swapped-hairpin and double-psi beta barrels.
AB - The core of swapped-hairpin and double-psi beta barrels is formed by duplication
of a conserved betaalphabeta element, suggesting a common evolutionary origin.
The path connecting the two folds is unclear as the two barrels are not
interconvertible by a simple topological modification, such as circular
permutation. We have identified a protein family whose sequence properties are
intermediate to the two folds. The structure of one of these proteins, Pyrococcus
horikoshii PhS018, is also built by duplication of the conserved betaalphabeta
element but shows yet a third topology, which we name the RIFT barrel. This
topology is widespread in the structure database and spans three folds of the
SCOP classification, including the middle domain of EF-Tu and the N domain of F1
ATPase. We propose that swapped-hairpin beta barrels arose from an ancestral RIFT
barrel by strand invasion and double-psi beta barrels by a strand swap. We group
the three barrel types into a metafold, the cradle-loop barrels.
PMID- 17027499
TI - Assessing computational amino acid beta-turn propensities with a phage-displayed
combinatorial library and directed evolution.
AB - Structure propensities of amino acids are important determinants in guiding
proteins' local and global structure formation. We constructed a phage display
library--a hexa-HIS tag upstream of a CXXC (X stands for any of the 20 natural
amino acids) motif appending N-terminal to the minor capsid protein pIII of M13KE
filamentous phage--and developed a novel directed-evolution procedure to select
for amino acid sequences forming increasingly stable beta-turns in the disulfide
bridged CXXC motif. The sequences that emerged from the directed-evolution cycles
were in good agreement with type II beta-turn propensities derived from surveys
of known protein structures, in particular, Pro-Gly forming a type II beta-turn.
The agreement strongly supported the notion that beta-turn formation plays an
active role in initiating local structure folding in proteins.
PMID- 17027500
TI - Structures of two bacterial prolyl-tRNA synthetases with and without a cis
editing domain.
AB - Prolyl-tRNA synthetases (ProRSs) are unique among synthetases in that they have
diverse architectures, notably the variable presence of a cis-editing domain
homologous to the freestanding deacylase proteins YbaK and ProX. Here, we
describe crystal structures of two bacterial ProRSs from the pathogen
Enterococcus faecalis, which possesses an editing domain, and from
Rhodopseudomonas palustris, which does not. We compare the overall structure and
binding mode of ATP and prolyl-adenylate with those of the archael/eukaryote-type
ProRS from Thermus thermophilus. Although structurally more homologous to YbaK,
which preferentially hydrolyzes Cys-tRNA(Pro), the editing domain of E. faecalis
ProRS possesses key elements similar to ProX, with which it shares the activity
of hydrolyzing Ala-tRNA(Pro). The structures give insight into the complex
evolution of ProRSs, the mechanism of editing, and structural differences between
prokaryotic- and eukaryotic-type ProRSs that can be exploited for antibiotic
design.
PMID- 17027501
TI - Kinking occurs during molecular dynamics simulations of small DNA minicircles.
AB - Recent experiments on minicircle formation suggest that a conformational
mechanism other than smooth deformation may be playing a role in enhancing DNA
flexibility. Both local base unpairing and kink formation have been suggested as
possible explanations. Although kinks within isolated DNA were proposed 30 years
ago, they have, until now, only been observed within DNA complexed with proteins.
In order to test how DNA behaves in the strong bending regime, we have carried
out molecular dynamics simulations of a 94 base pair minicircle in explicit
solvent with two different linking numbers, corresponding to a torsionally
relaxed state and a positively supercoiled state. The simulations suggest that
sharp kinks can indeed arise in small minicircles. The relaxed minicircle is
generally associated with a single kink, while two kinks occur with the
supercoiled state. No evidence is seen of base unpaired regions.
PMID- 17027502
TI - The structures of frataxin oligomers reveal the mechanism for the delivery and
detoxification of iron.
AB - Defects in the mitochondrial protein frataxin are responsible for Friedreich
ataxia, a neurodegenerative and cardiac disease that affects 1:40,000 children.
Here, we present the crystal structures of the iron-free and iron-loaded frataxin
trimers, and a single-particle electron microscopy reconstruction of a 24 subunit
oligomer. The structures reveal fundamental aspects of the frataxin mechanism.
The trimer has a central channel in which one atom of iron binds. Two
conformations of the channel with different metal-binding affinities suggest that
a gating mechanism controls whether the bound iron is delivered to other proteins
or transferred to detoxification sites. The trimer constitutes the basic
structural unit of the 24 subunit oligomer. The architecture of this oligomer and
several features of the trimer structure demonstrate striking similarities to the
iron-storage protein ferritin. The data reveal how stepwise assembly provides
frataxin with the structural flexibility to perform two functions: metal delivery
and detoxification.
PMID- 17027503
TI - Complex of calmodulin with a ryanodine receptor target reveals a novel, flexible
binding mode.
AB - Calmodulin regulates ryanodine receptor-mediated Ca(2+) release through a
conserved binding site. The crystal structure of Ca(2+)-calmodulin bound to this
conserved site reveals that calmodulin recognizes two hydrophobic anchor residues
at a novel "1-17" spacing that brings the calmodulin lobes close together but
prevents them from contacting one another. NMR residual dipolar couplings
demonstrate that the detailed structure of each lobe is preserved in solution but
also show that the lobes experience domain motions within the complex. FRET
measurements confirm the close approach of the lobes in binding the 1-17 target
and show that calmodulin binds with one lobe to a peptide lacking the second
anchor. We suggest that calmodulin regulates the Ca(2+) channel by switching
between the contiguous binding mode seen in our crystal structure and a state
where one lobe of calmodulin contacts the conserved binding site while the other
interacts with a noncontiguous site on the channel.
PMID- 17027504
TI - A potential protein-RNA recognition event along the RISC-loading pathway from the
structure of A. aeolicus Argonaute with externally bound siRNA.
AB - Argonaute proteins are key components of the RNA-induced silencing complex
(RISC). They provide both architectural and catalytic functionalities associated
with small interfering RNA (siRNA) guide strand recognition and subsequent guide
strand-mediated cleavage of complementary mRNAs. We report on the 3.0 A crystal
structures of 22-mer and 26-mer siRNAs bound to Aquifex aeolicus Argonaute (Aa
Ago), where one 2 nt 3' overhang of the siRNA inserts into a cavity positioned on
the outer surface of the PAZ-containing lobe of the bilobal Aa-Ago architecture.
The first overhang nucleotide stacks over a tyrosine ring, while the second
overhang nucleotide, together with the intervening sugar-phosphate backbone,
inserts into a preformed surface cavity. Photochemical crosslinking studies on Aa
Ago with 5-iodoU-labeled single-stranded siRNA and siRNA duplex provide support
for this externally bound siRNA-Aa-Ago complex. The structure and biochemical
data together provide insights into a protein-RNA recognition event potentially
associated with the RISC-loading pathway.
PMID- 17027505
TI - Ligand-release pathways in the pheromone-binding protein of Bombyx mori.
AB - Pheromone-binding proteins (PBP) supply olfactory neuron cells with pheromones by
binding the ligands they are tailored for and carrying them to their receptor.
The function of a PBP as an efficient carrier requires fast ligand uptake and
release. The molecular basis of the ligand-binding mechanism was addressed here
for the intriguing case of the PBP of the silk moth Bombyx mori. This PBP
completely encapsulates its ligand bombykol without displaying any obvious ligand
entrance/exit sites. Here, two opposite dissociation routes were identified as
the most likely entrance/exit paths by replica-exchange molecular dynamics,
essential dynamics, and force-probe molecular dynamics simulations. One of the
paths runs along a flexible front lid; the other along the termini at the back.
Calculated forces and energies suggest that both routes are physiologically
relevant. The multiplicity of pathways may reduce or tune the entropic barrier
for ligand binding.
PMID- 17027506
TI - Pheromone discrimination by the pheromone-binding protein of Bombyx mori.
AB - Pheromone-binding proteins are postulated to contribute to the exquisite
specificity of the insect's olfactory system, acting as a filter by
preferentially binding only one of the components of the natural pheromone. Here,
we investigated the possible discrimination of the two very similar components of
the natural pheromone gland from the silk moth, Bombyx mori, bombykol and
bombykal, by the only pheromone-binding protein (BmorPBP) known to be expressed
in the pheromone-detecting sensilla. Free-energy calculations and virtual docking
indicate that both bombykol and bombykal bind to BmorPBP with similar affinity.
In addition, in vitro competitive binding assays showed that both bombykol and
bombykal were bound by BmorPBP with nearly the same high affinity. While BmorPBP
might filter out other physiologically irrelevant compounds hitting the sensillar
lymph, discrimination between the natural pheromone compounds must be achieved by
molecular interactions with their cognate receptors.
PMID- 17027507
TI - Structure of complement component C2A: implications for convertase formation and
substrate binding.
AB - C2a provides the catalytic center to the convertase complexes of the classical
and lectin-binding pathways of complement activation. We determined two crystal
structures of full-length C2a, with and without a pseudo ligand bound. Both
structures reveal a near-active conformation of the catalytic center of the
serine protease domains, while the von Willebrand factor A-type domains display
an intermediate activation state of helix alpha7 with an open, activated metal
ion-dependent adhesion site. The open adhesion site likely serves to enhance the
affinity for the ligand C4b, similar to "inside-out" signaling in integrins.
Surprisingly, the N-terminal residues of C2a are buried in a crevice near helix
alpha7, indicative of a structural switch between C2 and C2a. Extended loops on
the protease domain possibly envelop the protruding anaphylatoxin domain of the
substrate C3. Together with a putative substrate-induced completion of the
oxyanion hole, this may contribute to the high substrate specificity of the
convertases.
PMID- 17027509
TI - IL-3, IL-5, and GM-CSF signaling: crystal structure of the human beta-common
receptor.
AB - The cytokines, interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte
macrophage colony stimulating factor (GM-CSF), are polypeptide growth factors
that exhibit overlapping activities in the regulation of hematopoietic cells.
They appear to be primarily involved in inducible hematopoiesis in response to
infections and are involved in the pathogenesis of allergic and inflammatory
diseases and possibly in leukemia. The X-ray structure of the beta common (betac)
receptor ectodomain has given new insights into the structural biology of
signaling by IL-3, IL-5, and GM-CSF. This receptor is shared between the three
ligands and functions together with three ligand-specific alpha-subunits. The
structure shows betac is an intertwined homodimer in which each chain contains
four domains with approximate fibronectin type-III topology. The two betac
subunits that compose the homodimer are interlocked by virtue of the swapping of
beta-strands between domain 1 of one subunit and domain 3 of the other subunit.
Site-directed mutagenesis has shown that the interface between domains 1 and 4 in
this unique structure forms the functional epitope. This epitope is similar to
those of other members of the cytokine class I receptor family but is novel in
that it is formed by two different receptor chains. The chapter also reviews
knowledge on the closely related mouse beta(IL-3) receptor and on the alpha
subunit-ligand interactions. The knowledge on the two beta receptors is placed in
context with advances in understanding of the structural biology of other members
of the cytokine class I receptor family.
PMID- 17027510
TI - Crystal structures and inhibitors of proteins involved in IL-2 release and T cell
signaling.
PMID- 17027511
TI - Structural studies of the interleukin-19 subfamily of cytokines.
AB - The interleukin-19 (IL-19) subfamily of cytokines is part of a larger family of
homologs of IL-10 that includes two groups of proteins: five viral cytokines, and
eight cellular cytokines, having quite different biological activities. Among
proteins of the latter group, IL-19, IL-20, IL-22, and IL-24 were suggested to
form a structurally unique IL-19 subfamily characterized by their structural
features and aggregation state as monomers. IFN-lambda1, IFN-lambda2, and IFN
lambda3 are likely to belong to this subfamily, and it is still not clear whether
IL-26 belongs to it or not. In spite of their differences in biological function,
all cellular homologs of IL-10 used for signaling a set of five overlapping
membrane-bound receptors: three long receptor chains (IL-20R1, IL-22R1, and IFN
lambdaR) and two short receptor chains (IL-20R2 and IL-10R2). Signal transduction
is initiated when a cytokine binds two receptor chains, one long and one short,
forming a ternary complex. Crystal structures of IL-19 and IL-22 showed that
these cytokines consist of seven amphipathic helices of different length
organized in helical bundle, covering an extensive hydrophobic core. Based on the
similarity of the structures with the structure of a single domain of IL-10, and
with the crystal structure of a binary IL-10/IL-10R1 complex, putative receptor
binding sites on the surface of IL-19 and IL-22 were identified. This chapter
summarizes the available structural data on the IL-19 subfamily of cytokines and
their putative ligand/receptor complexes.
PMID- 17027512
TI - Interleukin-22 and its crystal structure.
AB - Interleukin-22 (IL-22) is a cytokine that regulates the production of acute phase
proteins of the immunological response. On binding to its cognate receptor (IL
22R1), which is associated to the interleukin-10 receptor 2 (IL-10R2), IL-22
promotes activation of signal transducer and activator of transcription (STAT)
pathway and several other cellular responses. A soluble receptor termed
interleukin-22 binding protein (IL-22BP) is also able to bind to IL-22 as a
natural protein antagonist, and probably provides systemic regulation of IL-22
activity. This inflammatory response system is analyzed here in terms of its
molecular physiology and structural assembly. Three-dimensional (3D) model of IL
22 and structural basis of its interactions with the cognate receptors are
discussed.
PMID- 17027513
TI - Control of interleukin-2 gene transcription: a paradigm for inducible, tissue
specific gene expression.
AB - Interleukin-2 (IL-2) is a key cytokine that controls immune cell function, in
particular the adaptive arm of the immune system, through its ability to control
the clonal expansion and homeostasis of peripheral T cells. IL-2 is produced
almost exclusively by T cells in response to antigenic stimulation and thus
provides an excellent example of a cell-specific inducible gene. The mechanisms
that control IL-2 gene transcription have been studied in detail for the past 20
years and our current understanding of the nature of the inducible and tissue
specific controls will be discussed.
PMID- 17027514
TI - Transcription factors mediating interleukin-3 survival signals.
AB - Interleukin-3 (IL-3) is one of the major hematopoietic cytokines that regulate
the survival of hematopoietic cells of various lineages. Although the mechanism
underlying the survival effect of IL-3 has been investigated intensively for more
than a decade, our knowledge of the survival-signaling network remains
incomplete. Binding of IL-3 to its cognate receptors initiates rapid tyrosine
phosphorylation of Janus kinases (JAKs) and of signal transducer and activator of
transcription (STAT) proteins, as well as activation of the phosphatidylinositol
3 kinase (PI-3K)/Akt and Ras/Raf/MAPK kinase (MEK)/mitogen-activated protein
kinase (MAPK) pathways. These signals culminate in induction of a constellation
of antiapoptotic genes and prevent cell death from occurring. Thus IL-3 signaling
has substantial effects on kinase activation and gene transcription. Previous
articles have summarized the roles of these kinase pathways in cell proliferation
and survival. In this chapter, we will focus on the role of several newly
characterized transcriptional factors, which are targets of these initial kinase
cascades and bridge the gap between kinases and survival effector genes, in
transducing the IL-3 survival signal. The biological significance of the
existence of these multiple survival-specific transcription pathways will also be
discussed.
PMID- 17027515
TI - Interleukins and STAT signaling.
AB - Metazoan cells secrete small proteins termed cytokines that execute a variety of
biological functions essential for the survival of organisms. Binding of
cytokines that belong to the hematopoietin- or interferon-family, to their
cognate receptors on the surface of target cells, induces receptor aggregation,
which in turn sequentially triggers tyrosine-phosphorylation-dependent activation
of receptor-associated Janus-family tyrosine kinases (JAKs), receptors, and
signal transducers and activators of transcription (STATs). Phosphorylated STATs
form dimers that migrate to the nucleus, bind to cognate enhancer elements and
activate transcription of target genes. Each cytokine activates a specific set of
genes to execute its biological functions with a certain degree of redundancy.
Cytokine signals are, in general, transient in nature. Therefore, under normal
physiological conditions, initiation and attenuation of cytokine signals are
tightly controlled via multiple cellular and molecular mechanisms. Aberrant
activation of cytokine signaling pathways is, however, found under a variety of
patho-physiological conditions including cancer and immune diseases.
PMID- 17027516
TI - The newest interleukins: recent additions to the ever-growing cytokine family.
AB - Cytokines play a critical role in the control of the innate and adaptive immune
responses. The most recent additions to the ever-growing family of cytokines
include interleukin (IL)-27, IL-28A, IL-28B, IL-29, IL-31, IL-32, and IL-33. Many
of the newly identified cytokines and/or their specific receptors have been
identified using bioinformatics. The coming of age of this discipline has
coincided with completion of the sequencing of the human genome thus enabling the
identification of new uncharacterized proteins. The latest additions to the
interleukin family have shed new light on the intricacies of immune system
regulation. These novel cytokines have pleiotrophic actions ranging from
antiviral immunity to the regulation of Th2 immune responses. For example, the
discovery of IL-27 has greatly improved our understanding of the factors
regulating the polarization of the T helper cell responses and IL-31 appears to
be an important regulator of Th2 responses. On the other hand, IL-28 and IL-29
are considered to be critical for mounting an efficient antiviral response and IL
32 and IL-33, which are yet to be fully characterized, are emerging as important
components of the inflammatory response in allergy and autoimmunity. These new
cytokine/receptor combinations may therefore serve as novel targets for the
treatment and control of allergy, autoimmune diseases, and some cancers.
PMID- 17027517
TI - The interleukin-1 receptor family.
AB - The cytokines IL-1 and IL-18 are key molecules both in the innate and in the
adaptive immune response. Their activity is mediated by specific receptors
present on the membrane of target cells. It has become apparent that these
receptors are members of a larger family of related receptors, most of which are
apparently involved in the mechanisms of host defense. Thus, the large Toll/IL-1R
(TIR) superfamily encompasses the Ig domain family (IL-1 receptors, IL-18
receptors, and IL-1R-like receptors), the leucine-rich domain family [the Toll
like receptors (TLR) and similar receptors], and a series of TIR domain
containing intracellular adapter molecules. The TIR superfamily is defined by a
common intracellular TIR domain, involved in the initiation of signaling. A group
of TIR domain-containing adapters (MyD88, TIRAP, TRIF, and TRAM) are
differentially recruited to the Toll/IL-1 receptors, contributing to the
specificity of signaling. Recent studies have also begun to unravel the
mechanisms of negative regulation of the Toll/IL-1 receptors. The orphan receptor
TIR8/SIGIRR, a member of TIR superfamily, while unable to initiate signaling, can
negatively modulate the TIR-mediated responses. Other negative regulators of the
Toll/IL-1R family include T1/ST2, some soluble forms of TLR, and MyD88s. The
coordinated positive and negative regulation of the TIR activation ensures the
appropriate modulation of the innate and inflammatory responses and avoids the
risk of pathological derangement. This chapter will consider in detail the
characteristics and functional role of the Ig domain receptor subfamily in the
regulation of host defense and their possible role in pathology.
PMID- 17027518
TI - The IL-17 cytokine family.
AB - IL-17A and its receptor are the founding members of a recently described cytokine
family, with unique sequences and functions in the immune system and elsewhere.
Consisting of six ligands (IL-17A-F) and five receptors (IL-17RA-IL-17RE) in
mammals, these molecules have distinct primary amino acid structures with only
minimal homology to other cytokine families. By far the best studied of these
cytokines to date are IL-17A and its receptor, IL-17RA. IL-17A is produced
primarily by T cells, and is the hallmark cytokine of a newly defined T helper
cell subset that appears to be involved in generation of autoimmunity. Despite
its production by the adaptive immune system, IL-17A exhibits proinflammatory
activities similar to innate immune cytokines such as IL-1beta and TNF-alpha and
appears to play important and nonredundant roles in regulating granulocytes in
vivo. As a result, IL-17A also plays key roles in host defense. In contrast to
the restricted expression of IL-17A, the IL-17RA receptor is ubiquitously
expressed, and thus most cells are potential physiological targets of IL-17A.
This chapter describes the major molecular properties, biological activities, and
known signaling pathways of the IL-17 family, with an emphasis on IL-17A and IL
17RA.
PMID- 17027519
TI - NF-kappaB and cytokines.
AB - Cytokines represent a heterogeneous group of soluble mediators which are involved
in almost any physiological and pathological process. The release of many
cytokines and numerous of their biological activities are mediated by nuclear
factor-kappaB (NF-kappaB). NF-kappaB is a ubiquitous transcription factor which
is crucially involved in many biological processes, including tissue development
and maintenance of tissue homeostasis. NF-kappaB also controls apoptotic cell
death of both normal and malignant cells. Thus, it is a challenging target for
anticancer and anti-inflammatory strategies. However, it has been recognized that
NF-kappaB does not only influence many biological processes but also under
certain conditions the activities of NF-kappaB can be altered as well, for
example, by cytokines. This cross talk needs to be taken into account when
developing strategies targeting NF-kappaB for anticancer therapy.
PMID- 17027520
TI - IkappaB-zeta: an inducible regulator of nuclear factor-kappaB.
AB - The innate immune system responds to various microbial substances to elicit
production of cytokines, chemokines, and costimulatory molecules that regulate
activation of the acquired immune system. Although the transcription factor
nuclear factor (NF)-kappaB plays central roles in the induction, it remains to be
clarified how appropriate genes are selectively activated with appropriate timing
and duration by the multifunctional transcription factor after integration of
signals activated by invasion of various pathogens. IkappaB-zeta is barely
detectable in resting cells and is strongly induced upon stimulation of the
innate immune system. The induced IkappaB-zeta associates with the NF-kappaB
subunit in the nucleus and regulates its transcriptional activity both positively
and negatively depending on genes. Thus, the innate immune system utilizes NF
kappaB as a major transcription factor and modulates its activity in a gene
specific manner by the regulatory factor IkappaB-zeta, which is specifically
induced upon stimulation of the innate immune system. This multistep regulation
of the transcription would be fundamental in selective expression of genes upon
cell activation.
PMID- 17027521
TI - The inhibitory effects of interleukin-1 on growth hormone action during catabolic
illness.
AB - Growth hormone (GH) induces the expression of the anabolic genes responsible for
growth, metabolism, and differentiation. Normally, GH stimulates the synthesis of
circulating insulin-like growth factor-I (IGF-I) by liver, which upregulates
protein synthesis in many tissues. The development of GH resistance during
catabolic illness or inflammation contributes to loss of body protein, resulting
in multiple complications that prolong recovery and cause death. In septic
patients, increased levels of proinflammatory cytokines and GH resistance are
commonly observed together. Numerous studies have provided evidence that the
inhibitory effects of cytokines on skeletal muscle protein synthesis during
sepsis and inflammation are mediated indirectly by changes in the GH/IGF-I
system. Interleukin (IL)-1, a member of the family of proinflammatory cytokines,
interacts with most cell types and is an important mediator of the inflammatory
response. Infusion of a specific IL-1 receptor antagonist (IL-1Ra) ameliorates
protein catabolism and GH resistance during systemic infection. This suggests
that IL-1 is an important mediator of GH resistance during systemic infection or
inflammation. Consequently, a better understanding of the interaction between GH,
IL-1, and the regulation of protein metabolism is of great importance for the
care of the patient.
PMID- 17027522
TI - The role of the interleukin-6/gp130 signaling pathway in bone metabolism.
PMID- 17027523
TI - Regulation of osteoclast differentiation and function by interleukin-1.
AB - Interleukin-1 (IL-1) is a multifunctional cytokine that regulates various
cellular and tissue functions. Among tissues, bone is the most sensitive to IL-1.
IL-1 is a potent cytokine for bone resorption and participates in the multiple
steps of osteoclast recruitment, such as differentiation, multinucleation,
activation, and survival. On the other hand, considerable evidence has been
accumulated over the past 10 years to indicate that this cytokine plays key roles
in pathological bone destruction in a variety of human diseases, including
rheumatoid arthritis, osteoporosis, and periodontal disease. In this chapter, we
review the history of "IL-1 in bone" and the locus of this cytokine "from
laboratory bench to bedside." A better understanding of the role of IL-1 in
osteoclastic bone resorption would provide opportunities for developing new
therapeutics to treat diseases of the bone.
PMID- 17027524
TI - The role of IL-1 and IL-1Ra in joint inflammation and cartilage degradation.
AB - Interleukin (IL)-1 is a cytokine that plays a major role in inflammatory
responses in the context of infections and immune-mediated diseases. IL-1 refers
to two different cytokines, termed IL-1alpha and IL-1beta, produced from two
genes. IL-1alpha and IL-1beta are produced by different cell types following
stimulation by bacterial products, cytokines, and immune complexes.
Monocytes/macrophages are the primary source of IL-1beta. Both cytokines do not
possess leader peptide sequences and do not follow a classical secretory pathway.
IL-1alpha is mainly cell associated, whereas IL-1beta can be released from
activated cells after cleavage of its amino-terminal region by caspase-1. IL-1 is
present in the synovial tissue and fluids of patients with rheumatoid arthritis.
Several in vitro studies have shown that IL-1 stimulates the production of
mediators such as prostaglandin E(2), nitric oxide, cytokines, chemokines, and
adhesion molecules that are involved in articular inflammation. Furthermore, IL-1
stimulates the synthesis and activity of matrix metalloproteinases and other
enzymes involved in cartilage destruction in rheumatoid arthritis and
osteoarthritis. The effects of IL-1 are inhibited in vitro and in vivo by natural
inhibitors such as IL-1 receptor antagonist and soluble receptors. IL-1 receptor
antagonist belongs to the IL-1 family of cytokines and binds to IL-1 receptors
but does not induce any intracellular response. IL-1 receptor antagonist inhibits
the effect of IL-1 by blocking its interaction with cell surface receptors. The
use of IL-1 inhibitors in experimental models of inflammatory arthritis and
osteoarthritis has provided a strong support for the role of IL-1 in the
pathogeny of these diseases. Most importantly, these findings have been confirmed
in clinical trials in patients with rheumatic diseases. Additional strategies
aimed to block the effect of IL-1 are tested in clinical trials.
PMID- 17027525
TI - Cytokines in type 2 diabetes.
PMID- 17027526
TI - Release of interleukins and other inflammatory cytokines by human adipose tissue
is enhanced in obesity and primarily due to the nonfat cells.
AB - The white adipose tissue, especially of humans, is now recognized as the central
player in the mild inflammatory state that is characteristic of obesity. The
question is how the increased accumulation of lipid seen in obesity causes an
inflammatory state and how this is linked to the hypertension and type 2 diabetes
that accompanies obesity. Once it was thought that adipose tissue was primarily a
reservoir for excess calories that were stored in the adipocytes as
triacylglycerols. In times of caloric deprivation these stored lipids were
mobilized as free fatty acids and the insulin resistance of obesity was
attributed to free fatty acids. It is now clear that in humans the expansion of
adipose tissue seen in obesity results in more blood vessels, more connective
tissue fibroblasts, and especially more macrophages. There is an enhanced
secretion of some interleukins and inflammatory cytokines in adipose tissue of
the obese as well as increased circulating levels of many cytokines. The central
theme of this chapter is that human adipose tissue is a potent source of
inflammatory interleukins plus other cytokines and that the majority of this
release is due to the nonfat cells in the adipose tissue except for leptin and
adiponectin that are primarily secreted by adipocytes. Human adipocytes secrete
at least as much plasminogen activator inhibitor-1 (PAI-1), MCP-1, interleukin-8
(IL-8), and IL-6 in vitro as they do leptin but the nonfat cells of adipose
tissue secrete even more of these proteins. The secretion of leptin, on the other
hand, by the nonfat cells is negligible. The amount of serum amyloid A proteins 1
& 2 (SAA 1 & 2), haptoglobin, nerve growth factor (NGF), macrophage migration
inhibitory factor (MIF), and PAI-1 secreted by the adipocytes derived from a gram
of adipose tissue is 144%, 75%, 72%, 37%, and 23%, respectively, of that by the
nonfat cells derived from the same amount of human adipose tissue. However, the
release of IL-8, MCP-1, vascular endothelial growth factor (VEGF), TGF-beta1, IL
6, PGE(2), TNF-alpha, cathepsin S, hepatocyte growth factor (HGF), IL-1beta, IL
10, resistin, C-reactive protein (CRP), and interleukin-1 receptor antagonist (IL
1Ra) by adipocytes is less than 12% of that by the nonfat cells present in human
adipose tissue. Obesity markedly elevates the total release of TNF-alpha, IL-6,
and IL-8 by adipose tissue but only that of TNF-alpha is enhanced in adipocytes.
However, on a quantitative basis the vast majority of the TNF-alpha comes from
the nonfat cells. Visceral adipose tissue also releases more VEGF, resistin, IL
6, PAI-1, TGF-beta1, IL-8, and IL-10 per gram of tissue than does abdominal
subcutaneous adipose tissue. In conclusion, there is an increasing recognition
that adipose tissue is an endocrine organ that secretes leptin and adiponectin
along with a host of other paracrine and endocrine factors in addition to free
fatty acids.
PMID- 17027527
TI - Role of interleukin-13 in cancer, pulmonary fibrosis, and other T(H)2-type
diseases.
AB - Interleukin (IL)-13 plays a major role in various inflammatory diseases including
cancer, asthma, and allergy. It mediates a variety of different effects on
various cell types including B cells, monocytes, natural killer cells,
endothelial cells, and fibroblasts. IL-13 binds to two primary receptor chains IL
13Ralpha1 and IL-13Ralpha2. The IL-13Ralpha2 but not IL-13Ralpha1 chain binds IL
13 with high affinity and is overexpressed in a variety of human cancer cells
derived from glioma, squamous cell carcinoma of head and neck, and AIDS
associated Kaposi's sarcoma. We have also demonstrated that IL-13Ralpha2
expression is greatly increased in lung cells when mice were challenged
intranasally with bleomycin or Aspergillus fumigatus. In addition, IL-13Ralpha2
increased in surgical lung biopsies from patients with usual interstitial
pneumonia, nonspecific interstitial pneumonia, and respiratory bronchiolitic
interstitial pneumonia of unknown origin. Based on various studies, it is
concluded that IL-13Ralpha2-expressing cells are involved in various pulmonary
pathological conditions. In contrast, normal tissues such as brain, lung,
endothelial cells, and head and neck tissues express IL-13Ralpha1 chain, but show
only marginal expression of IL-13Ralpha2 chain. Thus, IL-13Ralpha2 chain may
serve as a novel biomarker for diseased cells such as cancer or fibrosis and a
target for receptor-directed therapeutic agents. To target IL-13R, a recombinant
fusion protein composed of IL-13 and a derivative of Pseudomonas exotoxin (PE)
has been produced. This cytotoxin termed as IL-13PE38QQR or IL-13PE38, or IL-13PE
is highly and specifically cytotoxic to a variety of human tumor cell lines. In
preclinical models of human glioblastoma, head and neck and AIDS-associated
Kaposi's cancer, IL-13PE has been found to have significant antitumor activity at
a tolerated dose. Several phase I clinical trials have been completed in patients
with recurrent malignant glioma. Recently a phase III clinical trial (PRECISE) in
patients with recurrent malignant glioma has been completed recruiting a total of
294 patients. IL-13PE cytotoxin has also shown a significant therapeutic effect
in preclinical bleomycin or A. fumigatus or Schistosoma mansoni-induced pulmonary
pathology including granulomatous fibrosis in mouse models. A clinical study in
these diseases has yet to be initiated.
PMID- 17027528
TI - Interleukins, inflammation, and mechanisms of Alzheimer's disease.
AB - Alzheimer's disease (AD) is the most common progressive neurodegenerative form of
dementia in the elderly and is characterized neuropathologically by
neurofibrillary tangles (NFT), amyloid neuritic plaques (NP), and prominent
synaptic and eventually neuronal loss. Although the molecular basis of AD is not
clearly understood, a neuroinflammatory process, triggered by Abeta42, plays a
central role in the neurodegenerative process. This inflammatory process is
driven by activated microglia, astrocytes and the induction of proinflammatory
molecules and related signaling pathways, leading to both synaptic and neuronal
damage as well as further inflammatory cell activation. Epidemiologic data as
well as clinical trial evidence suggest that nonsteroidal anti-inflammatory drug
(NSAID) use may decrease the incidence of AD, further supporting a role for
inflammation in AD pathogenesis. Although the precise molecular and cellular
relationship between AD and inflammation remains unclear, interleukins and
cytokines might induce activation of signaling pathways leading to futher
inflammation and neuronal injury. This chapter will discuss the association
between interleukins and neurodegeneration in AD and highlight the significance
of genetic and clinical aspects of interleukins in disease expression and
progression. As part of an emerging inflammatory signaling network underlying AD
pathogenesis, beta-amyloid (Abeta) stimulates the glial and microglial production
of interleukins and other cytokines, leading to an ongoing inflammatory cascade
and contributing to synaptic dysfunction and loss, and later, neuronal death.
Inflammatory pathways involving interleukin and cytokine signaling might suggest
potential targets for intervention and influence the development of novel
therapies to circumvent synaptic and neuronal dysfunction ultimately leading to
AD neurodegeneration.
PMID- 17027529
TI - Interleukin-2: from T cell growth and homeostasis to immune reconstitution of HIV
patients.
AB - Interleukin (IL)-2 was initially described as a major stimulant of T lymphocytes
in vitro. Later, the characterization of IL-2 knockout animals showed that the
ability to stimulate T cells could be replaced by other cytokines. In vivo, IL-2
plays a unique role in controlling lymphoproliferation. This is partly explained
by its role in the generation and maintenance of T regulatory cells (Treg). In
HIV-infected patients, the IL-2/IL-2 receptor (IL-2R) system is dysregulated. The
fact that IL-2 is underproduced along with defective IL-2R signaling detected in
patient lymphocytes, may explain the progressive impairment of the immune system
that occurs during chronic infection with this virus. These defects are partly
reversed by highly active antiretroviral therapy (HAART). However, in some
patients IL-2R defects persist and the CD4 counts remain low despite good control
of the viral load. These patients benefit from HAART given in conjunction with IL
2 therapy.
PMID- 17027530
TI - Asthma end points and outcomes: what have we learned?
AB - In spite of the wide prevalence of asthma and its substantial consequences, the
diagnosis and assessment of asthma has not been standardized, and the goals of
therapy currently are not being achieved. Our purpose is to help delineate what
the most important asthma end points are and what kinds of strategies we should
use to guide therapy. Comparison of numerous studies reveals that asthma measures
used routinely in the clinic, such as spirometric lung function, do not uniformly
correlate with asthma control. We cannot improve outcomes until we determine
which measures reveal the underlying disease process most clearly and at the same
time offer ease of performance during routine office visits. We propose that by
standardizing the way we collect and analyze data from our daily practice, we can
better define which measures reflect true asthma control. Such measures most
likely address a spectrum of changes occurring in the pathophysiology of asthma,
notably distal airway inflammation and hyperresponsiveness. Inflammation may
provide the best opportunity for assessment and treatment, because if it is
adequately addressed, airway sensitivity may improve, thereby reducing airway
obstruction and subsequently minimizing exacerbations. The fraction of exhaled
nitric oxide as a measure of inflammation is suggested as offering the best
combination of disease evaluation and practical implementation for improved
asthma outcomes.
PMID- 17027531
TI - Effectiveness of community-based injury prevention. Long-term injury rate levels,
changes, and trends for 14 Swedish WHO-designated Safe Communities.
AB - This study investigates the injury rate levels, changes, and trends between 1987
and 2002 for the 14 Swedish municipalities designated as WHO Safe Communities.
The injury rate was defined as the number of injured patients discharged from
hospital per 1000 persons. Injury rates were age standardised. Each municipality
was compared with its respective municipality group, according to a
classification of Sweden's 288 municipalities into nine groups based on numerous
structural parameters. The average injury rate levels for the 14 WHO-designated
Safe Community municipalities ranged from 11.54 to 19.09 per 1000 population
during the study period, which was defined as the time period during which a
municipality's injury prevention program has been operational. Eleven of 14
municipalities had higher levels than their corresponding municipality groups.
Five of the 14 municipalities "outperformed" their respective municipality groups
and achieved a greater relative injury rate decrease during the study period. The
trends for the 14 municipalities in relation to their municipality groups showed
an inconsistent pattern, with only four municipalities exhibiting overall
favourable trends for the study period.
PMID- 17027532
TI - Photocatalytic paper from colloidal TiO(2)--fact or fantasy.
AB - Photocatalytic paper encompasses a range of materials based on paper and nonwoven
fabrics which performs a function based on the light-activated catalytic activity
of colloidal TiO(2). The literature describing photocatalytic paper is surveyed,
including mechanisms, applications, limitations and future opportunities. The
technology is in its infancy with less than 10 patents and as many scientific
publications appearing over the last decade. The main applications described are
the destruction of organic molecules (mineralization) and photo-disinfection
(sterilization). These disclosures build upon a much larger literature describing
photochemical properties of TiO(2) both supported on non-cellulose substrates or
simply as suspended particles in water or air. Current photocatalytic paper
developments include methods to fix TiO(2) to cellulose substrates to minimize
photochemical damage to the paper. Another theme is the use of multiple
approaches, such as zeolites, for enhanced mineralization, and metals, such as
silver and copper, for enhanced photocatalytic disinfection.
PMID- 17027533
TI - Ninety-day mortality after bilateral hip arthroplasty.
AB - Despite lack of any studies, to our knowledge, bilateral total hip arthroplasty
(THA) is believed to carry higher perioperative mortality. The purpose of this
study is to investigate the incidence of mortality within 90 days of bilateral
THA in a major urban medical center. The incidence of 90-day mortality after 1
stage bilateral THA performed in 707 patients between 1995 and 2004 was
evaluated. A detailed analysis of our database was performed to determine which
bilateral THA patients died within 90 days of surgery. Every living patient who
had undergone bilateral hip arthroplasty was contacted. One patient (0.14%,
1/707) died within 90 days of 1-stage bilateral THA. The patient developed
spontaneous retroperitoneal hematoma requiring massive transfusion. The patient
died of multisystem failure 35 days after undergoing bilateral THA. One-stage
bilateral uncemented THA performed in a select group of healthy and young
patients carries an acceptable risk.
PMID- 17027534
TI - Steady-state penetration rates of electron beam-irradiated, highly cross-linked
polyethylene at an average 45-month follow-up.
AB - Steady-state penetration rates were determined on 53 total hip arthroplasties
with a minimum 3-year follow-up using electron beam highly cross-linked melted
polyethylene by determining the femoral head penetration occurring after the
first year in vivo. These data were compared with that of a matched control
group. The average steady-state penetration rate of the control group was 144 +/-
191 mum/y, significantly higher than that of the highly cross-linked polyethylene
group, 25 +/- 99 microm/y (P = .0001). Linear regression analysis indicated that
the magnitude of femoral head penetration did not increase with time in the cross
linked groups. Also, no significant difference existed between the steady-state
wear rates of the highly cross-linked groups with two head sizes (28 vs 32 mm, P
= .39).
PMID- 17027535
TI - Wear of highly cross-linked polyethylene acetabular cup in Japan.
AB - The wear characteristics of ultra-high-molecular-weight polyethylene acetabular
cups irradiated with 6.0 to 7.5 Gy of gamma-irradiation were studied in a hip
simulator and in vivo in 70 hips for 6 to 39 months. The linear wear was 2.5% to
4.5% of the wear seen in conventional polyethylene cups. A biphasic wear pattern
was observed over time with a relatively large wear in the first year and a
subsequent leveling of the wear rate curve. The linear wear rate in the second
phase (steady state) was 0.006 mm/y. The extent of decrease in clinical wear of
6.0-Mrad polyethylene (Aeonian, Kyocera Corp, Kyoto, Japan) cups is comparable
with the decrease of the in vitro wear measured by the hip simulation test.
PMID- 17027536
TI - Treatment of medial compartment arthritis of the knee: a survey of the American
Association of Hip and Knee Surgeons.
AB - Medial compartmental arthritis of the knee is a common orthopedic problem. This
study surveyed active members of the American Association of Hip and Knee
Surgeons on recommended surgical treatment of this condition. A response rate of
30.8% was obtained. One third of respondents (32.9%) reported patient age as the
most important factor in determining surgical treatment. Total knee arthroplasty
(89.2%) and arthroscopy (87.2%) were the most widely reported surgical
treatments. Most respondents (73.7%) rated experience as the primary basis in
determining factors for surgical recommendations. Case scenarios revealed age and
gender having significant bearing on treatment recommendations. These results
suggest that age and degree of deformity are 2 important considerations in
surgical treatment of medial compartment arthritis and, among this group of
respondents, influence the wide variety of treatment options.
PMID- 17027537
TI - Comparison between hand rasping and robotic milling for stem implantation in
cementless total hip arthroplasty.
AB - We evaluated the effects of conventional hand rasping and robotic milling on the
clinical and radiographic results of cementless total hip arthroplasty, with the
same computed tomography (CT)-based 3-dimensional preoperative planning using a
ROBODOC workstation (Integrated Surgical Systems, Davis, Calif). The robotic
milling group consisted of 78 hips, and the hand-rasping group 78 hips. The
radiographic findings from the preoperative planning and postoperative CT data
were evaluated using the most accurate CT images reconstructed by the ROBODOC
workstation. The robotic milling group showed significant superior Merle
D'Aubigne hip score at 2 years. In the robotic milling group, there were no
intraoperative femoral fractures, and a radiographically superior implant fit was
obtained. Hand rasping had the potential to cause intraoperative femoral
fractures, undersizing of the stem, unexpectedly higher vertical seating, and
unexpected femoral anteversion causing inferior implant fit.
PMID- 17027538
TI - Long-term results of the cementless ALLOCLASSIC hip arthroplasty system using a
28-mm ceramic head: with a retrospective comparison to a 32-mm head.
AB - One hundred twenty-four total hip arthroplasties in 119 patients, all performed
with the cementless ALLOCLASSIC hip arthroplasty system (SL stem and CSF cup;
Centerpulse, Winterthur, Switzerland), were analyzed retrospectively. In all
hips, a 28-mm head and an ultrahigh-molecular-weight polyethylene inlay were
used. Of the 124 hips, 81 could be investigated clinically and radiologically
after an average of 150.6 months (range, 133-169 months). Twenty-six patients (26
hips) died in the interim. One of these patients had septic cup loosening.
Seventeen hips (16 patients) were not available for follow-up because of health
reasons (12 hips in 11 patients), lack of cooperation (3 hips in 3 patients), or
loss to follow-up (2 hips in 2 patients). Of the 124 total hip arthroplasties, 4
cups were removed (2 aseptic and 2 septic loosening). No stem had to be removed.
If aseptic loosening is defined as the end point, the survival rate is 98.4% (95%
confidence interval, 93.8%-99.6%) for the cup and 100% for the stem after 157
months. If revision for any reason is defined as the end point, the survival rate
is 95.6% (95% confidence interval, 90.1%-98.3%). Before operation, the average
Harris Hip Score was 36.4 points (21-46). At time of follow-up, the average
Harris Hip Score was 89.7 points (54-100). Radiolucent lines and osteolyses were
found only seldom (mostly in the proximal stem zones).
PMID- 17027539
TI - Five-year follow-up of socket movements and loosening after revision with
impacted morselized allograft bone and cement: a radiostereometric and
radiographic analysis.
AB - In 1999, we reported on the 2-year results of a series of 21 first-time socket
revisions using impacted morselized allograft bone. Seven still migrated between
1.5 and 2 years. Seventeen remained for the current 5-year follow-up. No socket
had been rerevised. Five sockets showed signs of radiographic loosening. These 5
cases also exhibited radiographic signs of allograft resorption as well as high
rates of socket migration and rotation as measured by radiostereometric analysis.
Of the 6 remaining sockets that had migrated between 1.5 and 2 years, 3
stabilized and 3 were among those with signs of radiographic loosening. Fifteen
patients (15 hips) revealed pain reduction at the 5-year follow-up. Three had
slight pain on walking that disappeared immediately at rest (pain score 4). All
the others revealed either no pain (pain score 6) or slight pain that disappeared
with activity (pain score 5). No pattern of early socket migration according to
radiostereometric analysis could be identified, predicting later socket migration
or loosening. The rate of cases with signs of radiographic loosening (29%, 5/17)
was comparable to that reported by the Nijmegen group but the follow-up was
shorter in the current study. The rate of cases with signs of radiographic
loosening was comparable to both conventionally cemented socket revisions and
cementless revisions. The future will show if further sockets loosen and if the
loose sockets up to date will end up in rerevisions.
PMID- 17027540
TI - Comparative flexion after rotating-platform vs fixed-bearing total knee
arthroplasty.
AB - A retrospective review of rotating-platform (n = 113) and fixed-bearing (n = 100)
total knee arthroplasties at a minimum 2-year follow-up was performed. All
patients in both groups in this study had osteoarthritis and underwent surgery by
1 of the 2 senior authors at 1 of 2 institutions. A cruciate-retaining total knee
arthroplasty was implanted with patellar resurfacing in all cases. The only
difference between the 2 groups was the design of the tibial bearing and its
tibial tray. Through minimization of confounding variables relating to pathology,
surgeon, institution, soft-tissue balancing, and type of prosthesis, this study
isolates articular design as a variable. We could not demonstrate any significant
difference in knee flexion after either fixed-bearing or rotating-platform
cruciate-retaining total knee arthroplasty.
PMID- 17027541
TI - Polyethylene liner exchange of the Harris-Galante porous I and II acetabular
components without cement: results and complications.
AB - This study reviewed the long-term efficacy of the locking mechanism of the Harris
Galante porous (HGP) I and II acetabular components and the results and
complications of polyethylene liner exchange without cement. There were 400 HGP-I
components with a mean follow-up of 10 years (range, 2-19 years) and 78 HGP-II
components with 8 years of mean follow-up (range, 2-13 years). There has been
only 1 liner dislodgement (0.2%). Thirty-five hips (34 patients) have undergone
liner exchange without cement. The index acetabular component was implanted as a
primary procedure in 19 hips and a revision in 16 hips. No exchanged liner has
dislodged at a mean follow-up time of 5.1 years (range, 2-11 years). However,
there have been 7 patients (20%) with recurrent dislocation and all required
reoperation. Dislocation was significantly lower when an elevated rim liner was
used.
PMID- 17027542
TI - Patients' outcome after total hip arthroplasty: a comparison between the Western
Ontario and McMaster Universities index and the Oxford 12-item hip score.
AB - This prospective cohort study included 402 patients who had primary total hip
arthroplasty. The Western Ontario and McMaster Universities Index (WOMAC) and the
Oxford 12-item Hip Score (OHS) were used to assess patients preoperatively and at
1 year postoperation. The OHS has a higher responsiveness than the WOMAC in the
global scale and in the pain subscale. However, the WOMAC has better
responsiveness in its function scale. The point estimate of relative precision of
measuring postoperative quality of life shows that the OHS has a tendency toward
a better performance than the WOMAC; however, this finding is not statistically
significant. The OHS also demonstrates similar floor and ceiling effect patterns
as does the WOMAC. We recommend that the choice should depend on which scale
researchers are using to power a study.
PMID- 17027543
TI - In vivo oxidation of retrieved cross-linked ultra-high-molecular-weight
polyethylene acetabular components with residual free radicals.
AB - Wear of ultra-high-molecular-weight polyethylene (UHMWPE) contributes to debris
that can lead to periprosthetic osteolysis in total hip arthroplasty. Irradiation
not only decreases wear of UHMWPE but also generates residual free radicals that
can oxidize the UHMWPE in the long term. Melting or annealing is used to quench
the free radicals. Melting is more effective than annealing. We hypothesized that
the postirradiation annealed UHMWPE components would oxidize in vivo and that
postirradiation melted ones would not. We analyzed surgical explants of UHMWPE
acetabular liners. The irradiated and annealed explants showed embrittlement,
oxidation, and an increase in crystallinity. The irradiated and melted UHMWPE
explants showed no oxidation, no increase in crystallinity, and no embrittlement.
To prevent long-term chemical changes in highly cross-linked UHMWPE components,
the residual free radicals must be stabilized after irradiation, preferably by
melting and not annealing.
PMID- 17027544
TI - Midterm results of primary total knee arthroplasty using a dished polyethylene
insert with a recessed or resected posterior cruciate ligament.
AB - Use of a dished polyethylene insert in 114 total knee arthroplasties, all with
the posterior cruciate ligament resected or recessed, was retrospectively
studied. Patients were evaluated at a mean follow-up of 8.3 years. Mean range of
motion increased from 92 degrees to 111 degrees . Mean Knee Society pain and
function scores increased from 35.2 and 39.7 to 91.3 and 74.7, respectively.
WOMAC scores improved significantly in each category evaluated, including pain,
stiffness, and physical function. Kaplan-Meier survivorship was 95% at 10 years
(95% confidence interval, 82%-99%). The use of a dished polyethylene insert in
primary total knee arthroplasty provides good to excellent midterm results
regardless of whether the posterior cruciate ligament is recessed or sacrificed.
PMID- 17027545
TI - Lateral patellar contact after total knee arthroplasty: an analysis of the
effects on postoperative pain and outcome.
AB - Although medialization of the patellar component during primary total knee
arthroplasty (TKA) has been advocated for biomechanical reasons, this can lead to
lateral patellar contact with the femoral component. Using blinded radiographic
evaluations, we evaluated 980 consecutive primary TKAs performed from 1997 to
1998. The prevalence of lateral patellar contact in this series was found to be
46.1%. Lateral patellar contact was not correlated with significant differences
in our measures of outcome (knee score [P = .1066], functional score [P = .2457],
or range of motion [P = .2514]). The average pain score in knees with lateral
patellar contact was higher (48.1) (less pain) when compared with knees without
(46.7). Total knee arthroplasties without lateral patellar contact had a 1.61
times odds of experiencing postoperative pain compared with those TKAs with
lateral patellar contact (P = .0025).
PMID- 17027546
TI - Ten-year results of ALIZE acetabular cup with hydroxyapatite coating and AURA
hydroxyapatite-coated stem in total hip arthroplasty.
AB - One hundred seven total hip arthroplasties were done between 1991 and 1992 with
ALIZE acetabular cup with hydroxyapatite coating (Biomet France, Valence, France)
and AURA hydroxyapatite-coated stem (Biomet France) in 107 patients. The
articulation was ceramic on polyethylene for 102 patients and metal on
polyethylene for the remaining 5 patients. The mean follow-up of the series was
8.4 +/- 2.5 years. The mean preoperative Merle d'Aubigne hip functional score was
10.6 +/- 3 vs 15.8 +/- 1.8 at the latest follow-up. Sixty-three patients were
alive for the long-term follow-up at a mean of 9.67 +/- 0.25 years. Of the
patients, 98.5% were satisfied or very satisfied at the latest follow-up. Five
revisions were documented in these series: 1 for acetabular loosening, 2 for
traumatic ceramic head fracture, 1 for polyethylene replacement, and 1 for stem
replacement due to bone fracture. The mean wear rate was 0.076 +/- 0.043 mm/y
(<0.1 mm/y considered as the normal wear rate). The overall survival rate at 10
years was 95.6% +/- 2.1% using revision of either component as the end point.
PMID- 17027547
TI - Outcome of the contralateral hip in rapidly destructive arthrosis after total hip
arthroplasty: a preliminary report.
AB - We investigated the outcome of the contralateral hip in patients with rapidly
destructive arthrosis of the hip after total hip arthroplasty. Twenty-four
patients were included, and the mean duration of radiographic follow-up was 7.0
years (range, 3.8-17.8 years). To assess the capable parameters for predicting
the development of osteoarthritis, we evaluated the receiver operating
characteristic curves. Three (12.5%) of 24 patients developed osteoarthritis and
underwent total hip arthroplasty within 3.8 to 6.5 years. In these 3 patients,
both the acetabular-head index and the center-edge angle were significantly lower
than those in patients without osteoarthritis (P < .005). Based on the receiver
operating characteristic curves, both an acetabular-head index of less than 72%
and a center-edge angle of less than 16 degrees were considered to be associated
with the development of osteoarthritis.
PMID- 17027548
TI - Influence of polyethylene constraint on tibial component fixation in total knee
arthroplasty: follow-up report after 5 years.
AB - The influence of articulating surface design of AMK total knee prosthesis (DePuy,
Johnson & Johnson) on migration and radiographic outcome at 5 years was
evaluated. The knees were randomly allocated to receive a flat or a concave
insert with retention of the posterior cruciate ligament when preoperative
deformity was less severe and either a concave or a posterior-stabilized insert
with resection of the posterior cruciate ligament when deformity was more
pronounced. In 64 knees, migration was measured with radiostereometry. The
posterior-stabilized component displayed more varus-valgus tilting than the
concave insert. Other statistically significant differences in migration were not
seen. Radiolucent lines were frequently seen without differences between
prosthesis groups.
PMID- 17027549
TI - Less invasive total hip arthroplasty: description of a new technique.
AB - We describe a new technique and aim to justify its use in total hip arthroplasty.
The incision is short and there is minimal soft tissue dissection: piriformis and
most of quadratus femoris remain intact. A meticulous capsular repair is
performed. Patients are mobilized without restrictions. One hundred total hip
arthroplasties by the standard posterior approach (group 1) were compared with
100 by the less invasive approach (group 2). Minimum follow-up was 2 years. Mean
blood loss in group 1 was higher (P < .0001) and inpatient stay longer (P <
.0001). There was greater improvement in WOMAC scores for up to 1 year in the
less invasive group (P = .027). In conclusion, the less invasive approach is safe
and the functional benefits last up to 1 year.
PMID- 17027550
TI - Predicting pain after total knee arthroplasty.
AB - Six hundred twenty-two primary total knee arthroplasties were studied
prospectively in 512 patients. A group with no pain and one with severe pain at 5
years were statistically compared. The following were significant predictors of
poor pain outcomes: age below 60 (17%) compared with above 60 (7%, P < .05). The
first knee was most likely to be in the poor outcome group (13%) compared with
the second knee (6%). In contrast, patients who underwent simultaneous bilateral
arthroplasty faired better (2%, P < .01). Performing lateral release and
sacrificing the posterior cruciate ligament also significantly predicted for poor
pain outcomes but may have been influenced by selection bias. We conclude that
avoiding surgery in patients younger than 60 and choosing a simultaneous approach
to bilateral disease reduce the chance of poor pain outcomes.
PMID- 17027551
TI - Polished vs rough femoral components in grade A and grade C-2 cement mantles.
AB - The ideal surface for cemented femoral components remains controversial. Six
polished stems were compared with 6 rough stems both with good cement mantle and
also with poor cement mantles in a stair-climbing model. With good cement
mantles, both the polished and the rough stems were loose by 6 million cycles.
However, none were loose by radiographic criteria. With the poor cement mantle,
both stems became loose earlier and developed more micromotion, the polished
stems having significantly higher and earlier motion than the rough. Radiographic
evidence of debonding was not visible until the stems had motion of more than
2,000 microm. In the presence of a good cement mantle in this laboratory model
there was no significant difference in the development of micromotion under
fatigue stair-climbing conditions between a polished or grit-blasted femoral
component. However, in the presence of a poor cement mantle, the polished
components had earlier and higher micromotion. This study reinforces the
importance of centralization and cement technique, particularly if using a
polished surface finish.
PMID- 17027552
TI - A clinical, radiographic, and cost comparison of cerclage techniques: wires vs
cables.
AB - The cerclage technique is used to secure femoral fractures, allografts, and
plates. It is not clear whether wires or cables are better suited for this
technique. A retrospective radiographic review of the 6,460 total hip
arthroplasties done between 1986 and 2003 was performed. Wires/cables were used
in 249 hips. It was found that one cable was broken (0.92%) compared with 11
wires (1.72%) (P < .5373). It was found that there was no statistical difference
in Harris hip function or pain scores between patients with wires and those with
cables or between those with broken wires/cables and those without broken
wires/cables. The Luque wires, which cost 29.79 US dollars each, performed
equally to the cables, which cost 275.40 US dollars each, suggesting that wiring
may be the preferred cerclage technique.
PMID- 17027553
TI - Fracture of femoral component in a resurfacing total knee arthroplasty.
AB - We present a case of an unusual complication after a resurfacing total knee
arthroplasty. Fracture of the uncemented porous-coated femoral component occurred
4 years after its implantation. The mechanical axis was restored and collateral
ligament balance was achieved at the primary procedure. At revision, the femoral
component was found fractured at the junction of the trochlea with the medial
condyle, anteriorly to the medial peg. A thin layer of fibrous tissue was
interposed between bone and metal under the fracture area. Metallurgical analysis
of the fractured component revealed fatigue failure but no structural defect.
Lack of bony support and excessive cyclic loading led to fracture of the implant.
PMID- 17027554
TI - Fracture of a ceramic femoral head after ceramic-on-ceramic total hip
arthroplasty.
AB - A case of fracture of the ceramic head of a total hip arthroplasty is presented,
which was a total cementless arthroplasty with ceramic-on-ceramic articulation.
No history of trauma was observed. The arthroplasty was revised, and a new
cementless arthroplasty with a polyethylene insert and a metal head was inserted.
The result has been satisfactory.
PMID- 17027555
TI - Cruciate-retaining stemmed total knee arthroplasty for supracondylar
intercondylar femoral fractures in elderly patients: a report of three cases.
AB - The treatment of supracondylar or intercondylar femoral fractures in elderly
patients with gonarthrosis is a difficult problem. Primary total knee
arthroplasty (TKA) can be considered as a treatment modality for these patients,
and several authors have reported acceptable results with this option. They have
performed TKA using custom-made, hinged, or constrained components with long stem
for fracture reduction and stabilization. But use of hinged or constrained total
knee arthroplasties for dealing with supracondylar and intercondylar fractures
may be unnecessary, and an alternative is to use a cruciate-retaining stemmed
TKA. We report 3 elderly female patients who had supracondylar or intercondylar
femoral fractures and coexisting gonarthrosis treated by primary TKA with use of
a cruciate-retaining augmentable femoral component with stem extension. All
patients improved their ambulatory status and showed good knee function. We
believe that use of a cruciate-retaining type of component is a reasonable
alternative to the use of a more constrained prosthesis in the treatment for this
group of patients.
PMID- 17027557
TI - Late fatigue fracture of a modern cemented forged cobalt chrome stem for total
hip arthroplasty: a report of 10 cases.
PMID- 17027558
TI - Short- and long-term prognosis after acute myocardial infarction in men versus
women.
AB - The prevailing view is that women have a higher early mortality after acute
myocardial infarction (AMI) than men, but several studies have shown no
differences. Further, long-term differences have not been addressed widely. The
present study examined gender differences in short- and long-term prognoses after
AMI in The Netherlands. A nationwide cohort of 21,565 patients with a first
hospitalized AMI in 1995 was identified through linkage of the National Hospital
Discharge Register and the population register. Crude short- and long-term
mortalities were significantly higher in women than in men (28-day hazard ratio
[HR] 1.70, 95% confidence interval [CI] 1.58 to 1.82; 5-year HR 1.52, 95% CI 1.46
to 1.59). After adjustment for age, the risk difference was attenuated at 28 days
and even reversed at 5 years in favor of women (28-day HR 1.11, 95% CI 1.03 to
1.20; 5-year HR 0.94, 95% CI 0.90 to 0.99). When differences in other covariates
were also taken into account, the risk differences remained virtually the same.
To account for differences in reperfusion procedures, we repeated the analyses in
1,176 patients who underwent acute reperfusion therapy
(angioplasty/thrombolysis). Comparable, but not statistically significant, gender
differences were observed (28-day HR 1.06, 95% CI 0.65 to 1.74; 5-year HR 0.82,
95% CI 0.62 to 1.08). In conclusion, our findings in an unselected cohort
covering a complete nation indicate that the worse short- and long-term prognoses
after an AMI in women compared with men may largely be explained by differences
in age, whereas differences in co-morbidity, origin, infarct location, and
reperfusion therapy seem to contribute little.
PMID- 17027559
TI - Predictors of in-hospital mortality difference between male and female patients
with acute myocardial infarction.
AB - Many studies have demonstrated that, compared with men, women have increased long
and short-term mortality after acute myocardial infarction (AMI). The reasons
for this mortality difference remain in dispute. We analyzed baseline
characteristics, in-hospital management, and short-term outcomes of 1,246 men and
537 women with AMI to identify clinical variables that can predict the in
hospital mortality difference between genders. A higher in-hospital mortality was
found in women with AMI than in men (11.9% vs 6.9%, p <0.001). Women were
generally older, had a higher incidence of hypertension, diabetes mellitus, and
hyperlipidemia, and had a higher Killip class of cardiac function compared with
men. Reperfusion therapy and beta-receptor blockers were underused in women.
Using a multivariate logistic regression model, we identified age, history of
hypertension and diabetes mellitus, Killip class of cardiac function, and
administration of reperfusion therapy and beta-receptor blockers as significant
predictors of in-hospital mortality in patients with AMI, with odds ratios of
1.05 (95% confidence interval [CI] approximately 1.03 to 1.07), 1.65 (95% CI 1.12
to 2.41), 1.92 (95% CI 1.27 to 2.90), 3.62 (95% CI 2.88 to 4.56), 0.39 (95% CI
0.24 to 0.66), and 0.63 (95% CI 0.43 to 0.93), respectively. In conclusion, women
with AMI had a higher in-hospital mortality rate than did men, probably due to
older age, higher incidence of hypertension, diabetes mellitus, and
hyperlipidemia, a higher Killip class of cardiac function, and less utilization
of reperfusion therapy and beta-receptor blockers.
PMID- 17027560
TI - Echocardiographic and angiographic correlations in patients with cardiogenic
shock secondary to acute myocardial infarction.
AB - In patients with cardiogenic shock (CS) complicating acute myocardial infarction,
echocardiographic and angiographic findings are used to aid diagnosis, determine
prognosis, and guide management. The purpose of this analysis from the Should we
emergently revascularize Occluded Coronary arteries for Cardiogenic ShocK (SHOCK)
trial is to identify relations between the angiographic and echocardiographic
features of patients with CS. Such an analysis of the correlations between
echocardiographic and angiographic findings in patients with CS may provide
insights into the etiology and treatment of CS. In 302 randomized patients, an
echocardiogram and an angiogram before revascularization were available in 127
patients. Although the median ejection fraction derived by echocardiography and
left ventricular angiography was identical (30%), the positive correlation was
weak (R2 = 0.209, p = 0.019). Patients with a larger number of diseased vessels
had worse mitral regurgitation (MR) by echocardiography (p = 0.005). There was a
significant but weak association between left ventricular angiographic MR grade
and echocardiographic MR severity (R2 = 0.162, p = 0.015), but there was no
association between culprit vessel and degree of MR. In conclusion, worse
coronary artery disease is associated with more severe MR. Echocardiography and
angiography are valuable and result in similar estimated ejection fractions in a
large cohort, but there is wide variation between the techniques in patients.
PMID- 17027561
TI - Outcome of patients with adenosine-induced ST-segment depression but with normal
perfusion on tomographic imaging.
AB - Most patients with ST depression during adenosine infusion have reversible
perfusion defects by single-photon emission computed tomographic (SPECT)
perfusion images. Occasionally ST depression is observed in the setting of normal
perfusion images. The outcome of such patients is controversial. We identified 65
patients who underwent gated SPECT perfusion imaging with adenosine as the stress
agent. These patients were selected based on the following criteria: none had
previous myocardial infarction or coronary revascularization, all were in sinus
rhythm, and none had left bundle branch block. The 65 patients had normal SPECT
images but ischemic ST response (>or=1 mm ST depression). There were 52 women and
13 men who were 66 +/- 13 years of age. History of diabetes mellitus was present
in 16 patients (25%) and hypertension in 48 patients (74%). At a mean follow-up
of 24 months, there were no cardiac deaths or myocardial infarctions, and there
were 6 coronary revascularization procedures (2 coronary artery bypass graftings
and 4 coronary stentings of 1-vessel coronary disease). One patient died of
cancer. In conclusion, patients with no previous myocardial infarction or
coronary revascularization who have normal SPECT images have a benign outcome
despite the presence of ST depression (0% for death or myocardial infarction and
4.6%/year for coronary revascularization). Balanced ischemia could not be a
common cause for discordant perfusion and ST response.
PMID- 17027562
TI - Genotype-phenotype association of matrix metalloproteinase-3 polymorphism and its
synergistic effect with smoking on the occurrence of acute coronary syndrome.
AB - Matrix metalloproteinase-3 (MMP-3) degrades the extracellular matrix and may
contribute to the weakening of the plaque cap. To determine whether genotype
phenotype associations differed in different categories of acute coronary
syndrome, we enrolled 650 consecutive Taiwanese patients diagnosed with acute
coronary syndrome. Genotypic analysis was done on DNA using polymerase chain
reaction and direct sequencing on the 5 adenines (5A)/6 adenines (6A; -1,171 bp)
polymorphism in the MMP-3 gene promoter region. The frequency of the 5A
polymorphism was higher in patients with acute coronary syndrome, especially in
those with ST-elevation myocardial infarction (p <0.01). The number of 5A allele
polymorphisms was strongly associated with more complex coronary angiography
(diffuse score for 5A/5A vs 5A/6A vs 6A/6A, 6.6 +/- 1.2 vs 5.3 +/- 1.3 vs 4.6 +/-
1.1, all p values <0.05 in subgroup analysis) and higher plasma MMP-3 activity in
this acute coronary syndrome cohort (MMP-3 level for 6A/6A vs 5A/6A vs 5A/5A,
21.0 +/- 2.2 vs 23.3 +/- 2.1 vs 27.9 +/- 2.2 ng/ml, all p values <0.05 in
subgroup analysis). Multiple logistic regression analysis showed that this
polymorphism, in addition to hypertension, diabetes, and a history of smoking,
was an independent risk factor (odds ratio 2.2, 95% confidence interval 1.1 to
4.3, p = 0.02) for the occurrence of acute coronary syndrome. Further, carriers
of this polymorphism who smoked had a significantly increased (20-fold) risk of
acute coronary syndrome compared with nonsmoking noncarriers. In conclusion, the
MMP-3 5A/6A polymorphism is significantly associated with the occurrence of acute
coronary syndrome, MMP-3 activity, and severity of coronary atherosclerosis.
There is a synergistic effect between smoking and this genetic risk factor for
acute coronary syndrome.
PMID- 17027563
TI - Comparison of 30-day outcomes in patients <75 years of age versus >or=75 years of
age with acute myocardial infarction treated by primary coronary angioplasty.
AB - We reviewed 1,087 consecutive patients treated by primary coronary angioplasty
for acute myocardial infarction; 309 were >or=75 and 778 were <75 years of age.
Compared with the younger group, the older group had higher 30-day (8.1% vs 4.0%,
p = 0.0057) and cardiac (6.5% vs 3.6%, p = 0.038) mortality rates. Successful
reperfusion was achieved in the 2 groups at a similarly high rate (91.6% and
92.9%, p = 0.45). Successful compared with unsuccessful angioplasty decreased 30
day mortality rates in the older group (6.0% vs 30.8%, p <0.0001) and in the
younger group (3.2% vs 14.5%, p <0.0001). When reperfusion was successful, the
cardiac mortality rate in older patients was not significantly greater than that
in younger patients (4.6% vs 2.8%, p = 0.14). By multivariate analysis in all
1,087 patients, overt cardiogenic shock on admission (odds ratio 44.7, 95%
confidence interval 22.0 to 91.1, p <0.0001) and unsuccessful reperfusion (odds
ratio 9.40, 95% confidence interval 4.11 to 21.5, p <0.0001) were found to be
independent predictors of 30-day mortality, whereas age >or=75 years (odds ratio
1.79, 95% confidence interval 0.91 to 3.50, p = 0.090) was not. In conclusion,
aggressive angioplasty in older patients improves prognosis.
PMID- 17027564
TI - Polymer-based paclitaxel-eluting stents are superior to nonpolymer-based
paclitaxel-eluting stents in the treatment of de novo coronary lesions.
AB - Although polymer coating of coronary stents enables sufficient loading and
release of incorporated drugs, it has also been associated with potentially
negative effects. This study compared the clinical, angiographic, and
intravascular ultrasound (IVUS) outcomes of patients treated with polymer- versus
nonpolymer-based paclitaxel-eluting stents (PESs). Sixty-five consecutive
patients (70 de novo lesions) treated with polymer-based PESs (TAXUS, 1
microg/mm2 of paclitaxel; Boston Scientific Corp.) and 65 consecutive patients
(65 de novo lesions) treated with nonpolymer-based PESs (V-Flex Plus, 2.7
microg/mm2 of paclitaxel; Cook, Inc.) were enrolled in the study. Six-month
angiographic follow-up was performed on 54 lesions of the polymer-based PES group
and 51 lesions of the nonpolymer-based PES group. IVUS at angiographic follow-up
was performed in 61 of the first 70 included lesions. At 6-month IVUS follow-up,
mean intimal hyperplasia cross-sectional area was 2.36 +/- 1.60 mm2 in the
nonpolymer-based PES group versus 0.62 +/- 0.41 mm2 in the polymer-based PES
group (p = 0.003). Implantation of polymer-based PESs resulted in significantly
lower in-stent late lumen loss (0.22 +/- 0.27 vs 0.74 +/- 0.61 mm, respectively,
p <0.001). In-stent binary restenosis rate was 5% versus 20%, respectively (p
<0.001). Target lesion revascularization rate was 9% after implantation of
polymer-based PES versus 18% (p = 0.128) after implantation of nonpolymer-based
PES, and the major adverse cardiac event rate was 9% versus 23%, respectively (p
= 0.032). In conclusion, polymer-based PESs result in superior angiographic and
IVUS follow-up findings compared with nonpolymer-based PESs.
PMID- 17027565
TI - Twelve-month outcomes with a paclitaxel-eluting stent transitioning from
controlled trials to clinical practice (the WISDOM Registry).
AB - The WISDOM Registry tracked clinical outcomes in patients receiving a slow
release, polymer-based, paclitaxel-eluting stent during the transition from
randomized trials to commercial use in everyday interventional cardiology
practice. Although randomized trials of drug-eluting stents have demonstrated the
safety and effectiveness of these devices in less complicated, de novo lesions,
observation of long-term clinical outcomes is required to monitor safety as use
of this revolutionary technology expands to broader patient populations. In
total, 778 patients were enrolled at 22 sites in 9 countries where the TAXUS
paclitaxel-eluting stent first received market approval. Patients with de novo or
restenotic coronary lesions eligible for stenting were enrolled. Clinical follow
up was conducted by telephone at 3, 6, 9, and 12 months after the procedure to
capture reported stent thrombosis and major cardiac events (death, myocardial
infarction, and reintervention on the target lesion). Clinical follow-up at 12
months was completed for 92% of patients. The 12-month rate of physician-reported
major cardiac events was 5.2%, with a target lesion reintervention rate of 2.0%.
The low overall stent thrombosis rate of 0.6% included no stent thromboses >30
days after the index procedure. Low target lesion reintervention rates were also
observed in the high-risk subgroups: patients with diabetes (4.0%), vessels <2.5
mm (2.5%), lesions >20 mm (3.6%), and multiple stents in a lesion (1.4%). In
conclusion, the paclitaxel-eluting TAXUS slow-release stent exhibits long-term
safety and efficacy in uncomplicated and higher risk patients and lesions seen in
everyday clinical practice.
PMID- 17027566
TI - Influence of transmurality, infarct size, and severe microvascular obstruction on
left ventricular remodeling and function after primary coronary angioplasty.
AB - Infarct size has been considered an established marker of left ventricular (LV)
remodeling. We assessed the predictive value of myocardial/microvascular injury
assessed by delayed enhanced magnetic resonance imaging (MRI) on LV remodeling
and LV ejection fraction after primary coronary intervention (PCI) compared with
peak troponin levels, an established index of myocardial infarct size. We
performed MRI in 76 patients with first acute myocardial infarction 6 +/- 2 days
after successful PCI. Necrosis was judged as transmural when delayed enhancement
was extended to >or=75% of LV segment thickness. Severe microvascular obstruction
was identified as areas of late hypoenhancement surrounded by delayed
enhancement. Infarct size was expressed as an index by dividing the total
percentage of delayed enhancement involvement by the number of LV segments. LV
end-diastolic volume index and function were quantified by 2-dimensional
echocardiography at 6 +/- 1 months after acute myocardial infarction. Remodeling
was evaluated as a change in LV end-diastolic volume index at follow-up compared
with baseline. At univariate analyses, transmural necrosis, severe microvascular
obstruction, infarct size, and troponin level were correlated directly with
remodeling and inversely with LV function at follow-up (p <0.001). At multiple
regression, only transmural necrosis and troponin level remained independent
predictors of LV remodeling and function. With respect to troponin, transmural
necrosis improved the predictive power of LV remodeling (R2 for change = 0.19)
and function (R2 for change = 0.16). In conclusion, in patients with acute
myocardial infarction undergoing PCI, the amount of transmural necrosis as
assessed by MRI is a major determinant of LV remodeling and function, with
significant additional predictive value to infarct size and severe microvascular
obstruction.
PMID- 17027567
TI - Effect of plaque volume on subsequent vessel remodeling at edges of sirolimus
eluting stents.
AB - Serial (baseline and 9-month follow-up) intravascular ultrasound analysis was
performed at 5-mm reference segments immediately proximal and distal to the
sirolimus-eluting stent (SES) in 33 lesions. Proximal and distal reference
segments were divided into 1-mm subsegments. Between postintervention and follow
up intravascular ultrasound studies, there were significant decreases in the
lumen and increases in plaque & media areas in the subsegment closest to the
distal edge, with no change in external elastic membrane area. There was no
significant change in external elastic membrane, lumen, and plaque & media areas
within the other subsegments. At the nearest 1-mm subsegment from the proximal
and distal edges, baseline plaque & media area was associated with subsequent
vessel remodeling. In conclusion, a large amount of plaque at the SES edge may be
a risk of negative remodeling at follow-up (stent edge restenosis). It supports
the importance of "normal-to-normal" SES deployment.
PMID- 17027568
TI - Comparison of prevalence of unrecognized myocardial infarction and of silent
myocardial ischemia detected by a treadmill exercise sestamibi stress test in
patients with versus without diabetes mellitus.
AB - We investigated, in 287 patients with diabetes (71% men; mean age 63 +/- 8 years)
and 292 age- and gender-matched patients with diabetes, the prevalence of
unrecognized myocardial infarction (MI) and silent myocardial ischemia (SMI)
detected by a treadmill exercise sestamibi stress test. In the patients without a
history of MI, MI was diagnosed by treadmill exercise sestamibi stress test in 40
of 217 patients (18%) with diabetes and 16 of 224 patients (7%) without diabetes
(p <0.001). In patients with a history of angina, SMI was diagnosed in 35 of 98
patients (36%) with diabetes and 30 of 101 patients (30%) without diabetes (p =
NS). In patients without a history of angina, SMI was diagnosed in 62 of 189
patients (33%) with diabetes and 35 of 191 patients (15%) without diabetes (p
<0.001). In patients with 2 or 3 risk factors, SMI was diagnosed in 58 of 144
patients (40%) with diabetes and 41 of 142 patients (29%) without diabetes (p
<0.005). In patients with 0 or 1 risk factor, SMI was diagnosed in 39 of 143
patients (27%) with diabetes and 24 of 150 patients (16%) without diabetes (p
<0.02). In conclusion, patients with diabetes have a higher prevalence of
unrecognized MI and a higher prevalence of SMI without a history of angina than
patients without diabetes.
PMID- 17027569
TI - A population-based, cross-sectional comparison of lipid-related indexes for
symptoms of atherosclerotic disease.
AB - Current lipid guidelines recommend that therapy be targeted primarily at low
density lipoprotein (LDL) cholesterol, and that other lipid indexes may be used
as secondary or supplementary targets. Emerging data have suggested that measures
such as non-high-density lipoprotein (HDL) cholesterol, apolipoprotein-B, or the
total/HDL cholesterol ratio may be more predictive of cardiovascular risk than
LDL cholesterol. We conducted a cross-sectional analysis of data from the Third
National Health and Nutrition Examination Survey to directly compare the
strengths of the associations among various lipid-related indexes and clinical
features consistent with atherosclerotic disease. From approximately 9,500 data
sets in the overall analysis, the apolipoprotein-B/HDL cholesterol ratio emerged
as the strongest correlate (odds ratio 1.177 per 1 mg/dl increment, 95%
confidence interval 1.063 to 1.302, p <0.01), followed by the total or non-HDL
cholesterol/HDL cholesterol ratio (odds ratio for each 1.070 per 1 mg/dl
increment, 95% confidence interval 1.024 to 1.118, p <0.01), followed by the
triglyceride/HDL cholesterol ratio (odds ratio 1.033 per 1 mg/dl increment, 95%
confidence interval 1.011 to 1.056, p <0.01). Neither LDL cholesterol nor the
LDL/HDL cholesterol ratio correlated significantly. Parallel analyses comparing
tertile extremes and analyses in subgroups determined by gender, age, and body
mass index revealed similar findings. The LDL/HDL cholesterol ratio was only
significant for lean patients. In conclusion, these observations add to the
published data suggesting that LDL cholesterol may not be the best target of
lipid-lowering treatment strategies.
PMID- 17027570
TI - Comparison of body mass index versus waist circumference with the metabolic
changes that increase the risk of cardiovascular disease in insulin-resistant
individuals.
AB - This study compared the abilities of body mass index (BMI) and waist
circumference (WC) to identify resistance to insulin-mediated glucose uptake and
related metabolic abnormalities in 261 apparently healthy patients. Insulin
resistance and associated metabolic abnormalities occur more commonly in the
overweight/obese, and these changes increase the risk of cardiovascular disease
(CVD). Determining either their BMI or WC can identify patients more likely to
experience the adverse effects of excess adiposity on CVD risk, and the relative
clinical utility of these measurements is not clear. Therefore, insulin-mediated
glucose uptake was quantified in 261 apparently healthy adults by determining the
steady-state plasma glucose concentrations during the insulin suppression test;
the higher the concentration, the greater the defect in insulin action. The
fasting plasma glucose, triglyceride, and total, low-density lipoprotein, and
high-density lipoprotein cholesterol concentrations were also measured, and the
associations between these variables and the measurements of BMI and WC were
determined. The greater the degree of adiposity, the higher the steady-state
plasma glucose, fasting plasma glucose, and triglyceride concentrations,
irrespective of the index of adiposity used. However, increases in the total and
low-density lipoprotein cholesterol and decreases in the high-density lipoprotein
cholesterol concentrations were only seen in those with higher BMI values. In
conclusion, because BMI performed at least as well as WC in identifying
differences in insulin sensitivity and multiple CVD risk factors, either estimate
can be used to identify patients at increased CVD risk.
PMID- 17027571
TI - Relation of improvement in endothelium-dependent flow-mediated vasodilation after
rosiglitazone to changes in asymmetric dimethylarginine, endothelin-1, and C
reactive protein in nondiabetic patients with the metabolic syndrome.
AB - The mechanisms by which thiazolidinediones exert beneficial effects on the
endothelium are still not clear. We examined the effects of rosiglitazone on the
plasma markers of metabolic control (glucose, insulin, adiponectin, resistin, and
lipid profiles), markers of inflammation (high-sensitivity C-reactive protein
[CRP], interleukin-6, soluble CD40 ligand, intercellular adhesion molecule-1, and
vascular cell adhesion molecule-1), and markers of vasoreactivity (asymmetric
dimethylarginine [ADMA] and endothelin-1) and analyzed the relations between
changes in endothelium-dependent flow-mediated dilation of the brachial artery
and changes in these markers to elucidate their roles in mediating the vascular
protective effects of rosiglitazone. Of 70 nondiabetic patients who met a
modified National Cholesterol Education Program definition of the metabolic
syndrome, 35 were randomized to receive rosiglitazone (4 mg/day) and 35 to
receive placebo for 8 weeks. At study end, treatment with rosiglitazone had
significantly reduced plasma insulin (-25%, p = 0.004) and resistin (-16%, p
<0.001), increased adiponectin (164%, p <0.001), low-density lipoprotein
cholesterol (16%, p = 0.005), and apolipoprotein-B (14%, p = 0.003), and
decreased CRP (-30%, p = 0.005), soluble CD40 ligand (-20%, p = 0.014), ADMA (
16%, p <0.001), and endothelin-1 (-11%, p <0.001) concentrations and systolic and
diastolic blood pressures. Rosiglitazone treatment significantly improved flow
mediated dilation (p <0.001) and nitroglycerin-induced vasodilation (p = 0.001)
of the right brachial artery. On multivariate analysis, changes in ADMA,
endothelin-1, and CRP were independent predictors of improved endothelial
reactivity with rosiglitazone. In conclusion, we have, for the first time,
demonstrated the independent associations between the improvement in flow
mediated dilation and reductions in ADMA, endothelin-1, and CRP after 8 weeks of
treatment with rosiglitazone in nondiabetic patients with the metabolic syndrome.
These findings suggest that decreases in ADMA, endothelin-1, and CRP may serve as
possible mechanisms for the improvement in endothelial function conferred by
rosiglitazone treatment.
PMID- 17027572
TI - Sequelae of systemic hypertension in alcohol abstainers, light drinkers, and
heavy drinkers.
AB - A link exists between alcohol intake and increased blood pressure (BP), with many
studies showing increased hypertension prevalence in heavy drinkers. The harmful
and beneficial effects of alcohol can confound the study of the long-term risks
of alcohol-related hypertension. We therefore studied cardiovascular sequelae
separately in heavy drinkers, light drinkers, and abstainers among 127,212
subjects with BP and alcohol intake ascertained at 1978 to 1985 health
examinations. Subsequent cardiovascular end points included mortality risk,
hospitalization risk, and outpatient diagnosis of hypertension. Analyses were
performed for all subjects and stratified by 5 alcohol-drinking categories (from
never drinkers to >or=3 drinks/day). With <120/80 mm Hg as the referent, Cox
proportional hazards models were used to estimate relative risks and 95%
confidence intervals for 3 higher BP categories (120 to 129/80 to 84, 130 to
139/85 to 89, and >or=140/90 mm Hg). The covariates were age, gender, race, body
mass index, education, and smoking. The risk of all outcomes was progressively
higher for increasing BP categories, with a similarly increased risk for
abstainers, light drinkers, and heavy drinkers. The interaction tests for alcohol
and BP were not statistically significant for the mortality and hospitalization
outcomes. Interpretation was limited by an inability to separate subjects with
increased BP from alcohol consumption from those with other etiologies. In
conclusion, the data indicate that the risks of hypertension are similar
regardless of the amount of alcohol consumption.
PMID- 17027574
TI - Pulmonary embolism as a cause of death in adults who died with heart failure.
AB - Although heart failure (HF) is a known risk factor for pulmonary embolism (PE),
little is known about the frequency of death from PE in patients who die with HF.
This investigation was undertaken to determine the frequency of PE as the cause
of death in patients who died with HF on the basis of data from death
certificates, as listed by the United States Census Bureau. Among adults with HF
who died over the 19-year period of study, PE was the listed cause of death in
20,387 of 755,807 (2.7%). Assuming that the accuracy of death certificates was
only 26.7%, the rate of death from PE in these patients may have been as high as
10.1%. The frequency of death from PE in patients who died with HF decreased from
1980 to 1998. In conclusion, the estimated death rate from PE in patients who
died with HF is 3% to 10%. A decrease over 2 decades in the proportion of deaths
from PE in such patients is compatible with the increasing and effective use of
antithrombotic prophylaxis.
PMID- 17027573
TI - Effect of marital quality on eight-year survival of patients with heart failure.
AB - Recent evidence suggests that psychosocial factors such as self-efficacy,
psychological distress, perceived social support, and marital quality have
prognostic significance for morbidity and mortality after heart failure.
Previously, we reported that interview and observational measures of marital
quality obtained from 189 patients with heart failure (139 men and 50 women) and
their spouses predicted all-cause patient mortality during the next 4 years,
independent of the baseline illness severity (New York Heart Association class).
We present additional follow-up results for this sample, with Cox regression
analyses showing that a couple-level composite measure of marital quality
continued to predict survival during an 8-year period (p <0.001), especially when
the patient was a woman, and did so substantially better than individual (patient
level) risk and protective factors, such as psychological distress, hostility,
neuroticism, self-efficacy, optimism, and breadth of perceived emotional support.
In conclusion, relationship factors may be especially relevant in managing a
difficult chronic condition such as heart failure, which makes stringent and
complex demands on patients and their families.
PMID- 17027575
TI - A novel prognostic index to determine the impact of cardiac conditions and co
morbidities on one-year outcome in patients with heart failure.
AB - Prognostic stratification is relevant in clinical decision making in heart
failure (HF). Predictors identified during hospitalization or in clinical trials
may be unrepresentative of HF in the community. The aim of this study was to
derive and validate, in different clinical settings, a risk stratification model
for the prediction of stable HF outcomes. The study included 807 patients, 350
enrolled at discharge from the hospital (44%), 309 in the outpatient clinic
(38%), and 148 in the home-care setting (18%). There were 292 patients in the
derivation cohort and 515 in the validation cohort. A multivariate logistic
analysis was performed to obtain the CardioVascular Medicine Heart Failure (CVM
HF) index. One-year mortality was 20.8% in the derivation cohort and 20.7% in the
validation cohort. The CVM-HF index included cardiac conditions and co
morbidities and stratified the 1-year mortality risk as low (death rate 4%),
average (32%), high (63%), and very high (96%). The area under the curve of the
receiver-operating characteristic curve was 0.844 (95% confidence interval [CI]
0.779 to 0.89) for the derivation cohort and 0.812 (95% CI 0.76 to 0.86) for the
validation cohort. Model performance was equally good in the 3 different HF
settings. In a subgroup of 409 patients, the CVM-HF index (area under the curve
0.821, 95% CI 0.79 to 0.89) outperformed the most-used prognostic models (the
Charlson index and the Heart Failure Risk Scoring System). In conclusion, the CVM
HF index, a novel prognostic model that is easy to derive and applicable to
unselected patients, may represent a valuable tool for the prognostication of
stable HF outcomes.
PMID- 17027576
TI - Are left ventricular diastolic function and diastolic asynchrony important
determinants of response to cardiac resynchronization therapy?
AB - Cardiac resynchronization therapy (CRT) has been shown to reduce symptoms and
reverse left ventricular (LV) remodeling. It is not known, however, whether
diastolic function will improve after CRT and diastolic asynchrony will predict
LV reverse remodeling. Seventy-six patients (mean age 65 +/- 12 years, 74% men)
who received CRT were studied at baseline and after 3 months. Diastolic function
was assessed by transmitral Doppler and tissue Doppler imaging. LV systolic and
diastolic asynchrony were assessed by the time to peak myocardial contraction
(Ts) and early diastolic relaxation (Te) using the 6 basal, 6 mid-segmental
model. There were 42 responders (55%) with LV reverse remodeling (defined as a
reduction of LV end-systolic volume >or=15%). Parameters of systolic function
were significantly improved only in the responders. For diastolic function, there
were reductions of transmitral E velocity in the 2 groups, without any change in
atrial velocity or the E/A ratio. Tissue Doppler imaging revealed that myocardial
early diastolic velocity was unchanged in responders but was significantly
worsened in nonresponders. The systolic asynchrony index (the SD of Ts of 12 LV
segments) correlated significantly with LV reverse remodeling (r = -0.64, p
<0.001) but not the diastolic asynchrony index (the SD of Te of 12 LV segments)
(r = -0.10, p = NS). The systolic asynchrony index was the only independent
predictor of reverse remodeling (beta = -0.99, 95% confidence interval -1.41 to
0.58, p <0.001). In conclusion, CRT improves systolic function and systolic
asynchrony but has a neutral effect on diastolic function and diastolic
asynchrony. LV reverse remodeling response is determined by the severity of
prepacing systolic asynchrony but not diastolic asynchrony or the diastolic
filling pattern.
PMID- 17027577
TI - Value of mitral valve tenting volume determined by real-time three-dimensional
echocardiography in patients with functional mitral regurgitation.
AB - This study sought to evaluate mitral valve tenting volume (TnV) as a clinical
parameter using real-time 3-dimensional echocardiography in patients with
functional mitral regurgitation (MR). In 27 patients with functional MR and 4
controls without mitral disease, real-time 3-dimensional echocardiographic images
were obtained to measure TnV frame by frame from presystole to end-systole. The
maximal and minimal TnVs during systole were identified in each patient, and
mitral annular areas and tenting heights were also measured. Using 2-dimensional
echocardiography, tenting area (TnA) was measured from the apical long-axis,
apical 4-chamber, and apical 2-chamber views. The regurgitant orifice area was
measured by the proximal isovelocity surface area method. Maximal and minimal
TnVs occurred at the time of 2 +/- 6% and 78 +/- 6% of whole systolic duration,
respectively, and the systolic percentage change of TnV was related to that of
tenting height but not to that of mitral annular area. TnA on the long-axis
images was significantly larger than that on the 4- and 2-chamber images (2.5 +/-
1.4 vs 1.7 +/- 1.3 and 1.9 +/- 1.4 cm(2), respectively, p <0.001). Regurgitant
orifice area was significantly correlated with maximal TnV (r = 0.90), minimal
TnV (r = 0.86), and TnA on the long-axis (r = 0.79), 4-chamber (r = 0.75), and 2
chamber (r = 0.73) images. Among minimal TnV and 3 TnAs, minimal TnV was the only
independent determinant of regurgitant orifice area (p <0.001). Minimal TnV
>or=3.90 ml identified significant functional MR with a sensitivity of 86% and a
specificity of 100%. In conclusion, TnV derived from real-time 3-dimensional
echocardiography is a preferable novel single index for assessing mitral valve
tethering in functional MR to TnA that is dependent on the location of 2
dimensional planes.
PMID- 17027578
TI - Comparison of the pattern of aortic dilation in children with the Marfan's
syndrome versus children with a bicuspid aortic valve.
AB - Marfan's syndrome (MS) and bicuspid aortic valves (BAVs) are associated with
aortic dilation. Despite their histologic similarities, the 2 diseases differ
with regard to the location of maximal aortic dilation. Echocardiographic
analysis of aortic dimensions was performed in children with MS, children who had
aortic dilation in the setting of nonstenotic BAVs (peak gradient <16 mm Hg), and
healthy controls. Data on 25 patients with MS, 31 with BAVs, and 65 controls were
analyzed. Subjects with BAVs had greater dimensions at all levels of the aortic
root compared with normal controls. Patients with BAVs also had greater dilation
than those with MS at the level of the annulus and the ascending aorta, with
dilation often extending cranially beyond the region of measurement. Conversely,
patients with MS had more focal dilation at the sinuses of Valsalva compared with
controls and patients with BAVs. In conclusion, despite similar histologic
abnormalities, the anatomic pattern of aortic dilation differs in children with
MS and BAVs.
PMID- 17027579
TI - Morphology and function of the bicuspid aortic valve with and without coarctation
of the aorta in the young.
AB - This study sought to determine the morphology and function of bicuspid aortic
valves (BAVs) with and without coarctation of the aorta (CoA) in a young
population. The transthoracic echocardiograms of 117 patients with BAVs and 62
patients with CoA were retrospectively reviewed and compared with normal
transthoracic echocardiographic results. In each patient, the area subtended by
the aortic cusps and valve and the diameters of the aortic root at different
levels were measured, and additionally in each BAV, the type of cusp fusion and
the presence and degree of aortic stenosis and/or regurgitation were evaluated.
The median age of patients with BAVs was 4 years (range 0 days to 34 years), and
the median age of patients with CoA was 1.9 years (range 0 days to 16.5 years).
BAVs with right and left coronary cusp fusion were significantly associated with
CoA (p <0.0001) and cardiac anomalies (p <0.0001), whereas BAVs with noncoronary
and right coronary cusp fusion were affected by valvar dysfunction (p <0.001).
Compared with normal tricuspid aortic valves, BAVs had aortic root dilation, even
in patients with no hemodynamic disturbance, particularly at the level of the
ascending aorta (p <0.0001); the difference was still significant comparing BAVs
and CoA with tricuspid aortic valves and CoA (p <0.0001). In conclusion,
different morphologies of BAVs are associated with different cardiac
abnormalities, valvar function, and aortic root dilation. Although detectable
early in life, valvar dysfunction and aortic root dilation progress with age.
PMID- 17027580
TI - Frequency of circumferential pericardial effusion by echocardiography in adults
with foramen ovale type atrial septal defect versus ventricular septal defect.
AB - Many published reports have described pericardial effusions in patients with
secundum atrial septal defects. This study investigated their associated
prevalence echocardiographically using 40 patients with isolated ventricular
septal defects as controls in an adult patient population. Pericardial effusions
accompanied atrial septal defects in 13 patients and ventricular septal defects
in only 3 patients (p <0.0001). In conclusion, pericardial effusions are much
more common (p <0.005) with uncomplicated secundum atrial septal defects than
with uncomplicated ventricular septal defects.
PMID- 17027581
TI - Association between the ankle-brachial index and carotid intimal medial thickness
in the Rancho Bernardo Study.
AB - Previous cross-sectional studies have demonstrated significant associations
between the ankle-brachial index (ABI) and carotid intimal medial thickness
(IMT). In a longitudinal study, 637 participants who had ABI measurements from
1992 to 1994 were tested for carotid IMT an average of 4.8 years later. Mean age
was 72.5 years; 60% were women. More than half (51%) were hypertensive, whereas
28% had dyslipidemia, 56% were past or current smokers, and 6% had diabetes. The
mean +/- SD ABI and IMT were 1.06 +/- 0.13 and 1.28 +/- 0.44 mm, respectively.
Mean age- and gender-adjusted IMTs for the ABI groups of or=20% and
or=20% and or=20% and histidine (R192H) by cardiac specific
expression of the mutated protein (cTnI(193His) in mouse sequence) in transgenic
mice. Heart tissue sections revealed neither significant hypertrophy nor
ventricular dilation in cTnI(193His) mice. The main functional alteration
detected in cTnI(193His) mice by ultrasound cardiac imaging examinations was
impaired cardiac relaxation manifested by a decreased left ventricular end
diastolic dimension (LVEDD) and an increased end diastolic dimension in both
atria. The cardiac ejection fraction (EF) was not significant changed in 6- to 8
week-old cTnI(193His) mice, however, the EF was significantly decreased in
cTnI(193His) mice at age of 11 months. These data indicate that individual
genetic conditions and environmental factors participate together in the
development of the cTnI mutation based-cardiac muscle disorders. This mouse model
provides us with a tool to further investigate the pathophysiology and the
development of RCM.
PMID- 17027634
TI - Conformational and functional studies of gomesin analogues by CD, EPR and
fluorescence spectroscopies.
AB - The aim of this work was to examine the bioactivity and the conformational
behavior of some gomesin (Gm) analogues in different environments that mimic the
biological membrane/water interface. Thus, manual peptide synthesis was performed
by the solid-phase method, antimicrobial activity was evaluated by a liquid
growth inhibition assay, and conformational studies were performed making use of
several spectroscopic techniques: CD, fluorescence and EPR. [TOAC(1)]-Gm;
[TOAC(1), Ser(2,6,11,15)]-Gm; [Trp(7)]-Gm; [Ser(2,6,11,15), Trp(7)]-Gm; [Trp(9)]
Gm; and [Ser(2,6,11,15), Trp(9)]-Gm were synthesized and tested. The results
indicated that incorporation of TOAC or Trp caused no significant reduction of
antimicrobial activity; the cyclic analogues presented a beta-hairpin
conformation similar to that of Gm. All analogues interacted with negatively
charged SDS both above and below the detergent's critical micellar concentration
(cmc). In contrast, while Gm and [TOAC(1)]-Gm required higher LPC concentrations
to bind to micelles of this zwitterionic detergent, the cyclic Trp derivatives
and the linear derivatives did not seem to interact with this membrane-mimetic
system. These data corroborate previous results that suggest that electrostatic
interactions with the lipid bilayer of microorganisms play an important role in
the mechanism of action of gomesin. Moreover, the results show that hydrophobic
interactions also contribute to membrane binding of this antimicrobial peptide.
PMID- 17027636
TI - Identification of conserved lentiviral sequences as landmarks of genomic
flexibility.
AB - Considering that recombinations produce quasispecies in lentivirus spreading, we
identified and localized highly conserved sequences that may play an important
role in viral ontology. Comparison of entire genomes, including 237 human, simian
and non-primate mammal lentiviruses and 103 negative control viruses, led to
identify 28 Conserved Lentiviral Sequences (CLSs). They were located mainly in
the structural genes forming hot spots particularly in the gag and pol genes and
to a lesser extent in LTRs and regulatory genes. The CLS pattern was the same
throughout the different HIV-1 subtypes, except for some HIV-1-O strains. Only
CLS 3 and 4 were detected in both negative control HTLV-1 oncornaviruses and D
particle-forming simian viruses, which are not immunodeficiency inducers and
display a genetic stability. CLSs divided the virus genomes into domains allowing
us to distinguish sequence families leading to the notion of 'species self'
besides that of 'lentiviral self'. Most of acutely localized CLSs in HIV-1s (82%)
corresponded to wide recombination segments being currently reported.
PMID- 17027637
TI - Midgut glycosidases activities in monophagous larvae of Apollo butterfly,
Parnassius apollo ssp. frankenbergeri.
AB - Parnassius apollo (Lepidoptera, Papilionidae) declines on numerous localities all
over Europe. Its local subspecies frankenbergeri, inhabiting the Pieniny Mts
(southern Poland) and successfully recovered from extinction, is monophagous in
larval stage. In natural conditions, it completes development on the orpine Sedum
telephium ssp. maximum. Since proper quality and quantity of necessary
nutritional compounds of the food plant ensure developmental success, the
digestive processes in the insect midgut should reflect adaptation to a specific
food source. The paper presents, for the first time, the activity of detected
glycolytic enzymes in midgut tissue and liquid gut contents of the L4 and L5
instars of P. apollo larvae. alpha-Amylase plays the main role in utilization of
carbohydrates, contrary to cellulase activity. Saccharase seems to be the main
disaccharidase, and high activity of beta-glycosidase enables hydrolysis of the
plant glycosides. Trehalase activity was unexpectedly low and comparable to those
of cellobiase and lactase. alpha-Amylolytic and other glycolytic activities
indicate that larvae utilize starch and other carbohydrate compounds as energy
sources. Possible use of some plant allelochemicals as energy sources by Apollo
larvae is discussed.
PMID- 17027638
TI - [Impact of green tea on oxidative stress induced by ammonium metavanadate
exposure in male rats].
AB - Transitional metals, as vanadium, are known to exert noxious effects by
generating oxidative stress. Addition of antioxidants in the diet could decrease
the cytotoxic effect related to the oxidative stress. The present study, carried
out in Wistar rats, is a contribution to the evaluation of protective effects of
green tea Camellia sinensis, which is known to be rich in antioxidant compounds
(polyphenols...). Rats were divided into four groups: (C) was control, (V) was
given ammonium metavanadate (AMV), (TH) was given herbal tea as drink (66 g/l)
and TH + V was given tea and metavanadate. Group (TH) was given herbal tea one
month before vanadium treatment. Metavanadate was daily i.p. injected (5 mg
NH4VO3/kg body weight) for 10 days. (C) and (TH) groups received i.p. injections
of 0.9% NaCl during the same period. Changes in lipid peroxidation levels (TBARS)
in kidney, liver and testes, serum concentrations of vitamins E and A and
superoxidismutase (SOD) and catalase (CAT) activities in blood cells were
determined. One month pre-treatment with green tea, followed by 10 days of
treatment (TH) did not change TBARS in liver and testes as compared to controls,
but induced a clear decrease of TBARS in kidneys. Intraperitoneal administration
of AMV to rats (V) induced a time-dependant increase of TBARS in kidney, liver
and testes that was lowered in rats (V + TH) drinking tea. Vitamin E
concentrations were found to be drastically decreased from day 1 to 10 in rats
(V). Vitamin A concentration was decreased at day 10 only. Drinking tea lowered
AMV inhibitory effects in rats (V + TH), and conversely an increase of vitamins A
and E concentrations were found at day 10. SOD and catalase activities were found
increased in the blood cells from day 1 to day 5 and conversely decreased at day
10. In contrast, associated to green tea, AMV did not affect SOD and catalase
activities compared to controls.
PMID- 17027639
TI - Spatio-temporal dynamics of the nematode Anguillicola crassus in Northeast
Tunisian lagoons.
AB - Anguillicola crassus, parasite nematode of the European eel Anguilla anguilla,
was recorded for the first time in Tunisia (1999) in the Ichkeul lagoon. Its
distribution has since spread toward Bizerte and Ghar El Melh lagoons. The
monthly epidemiological survey reveals that A. crassus exists throughout the year
in the Ichkeul lagoon. In this lagoon, its prevalence is low in winter (12% in
December), with a marked increases in the spring reaching a maximum in March
(35%), before it starts to decrease in summer with a minimum in July (4.35%),
which in turn is followed by a pronounced new rise in autumn (30% in November).
However, mean intensity values do not show such a marked variation. The majority
of the values are between 1 and 1.5 parasites per host. In the Bizerte and Ghar
El Melh lagoons, the presence of this nematode is limited only to one to three
months. Investigations in the Tunis lagoon did not reveal until now the presence
of A. crassus. It has been observed that the length of the eel influences the
prevalence values: A. crassus becomes less common if the length of the eel
increases. Comparatively with the global epidemiological values of A. crassus
signalled subsequently (1999) in the Ichkeul lagoon, we note that the present
values record a clean increase.
PMID- 17027640
TI - [Implication of glutamate, isocitrate and malate deshydrogenases in nitrogen
assimilation in the cadmium-stressed tomato].
AB - Tomato seedlings grown on nitric medium and treated with various cadmium
concentrations (0 to 50 microM) were used. Results obtained show that cadmium
remains predominantly located in the roots, which then seem to play the role of
trap-organs. Increasing cadmium concentration in the medium leads particularly to
a decrease in NO3- accumulation, together with a decrease in the activity of
glutamine synthetase and in the quantity of plastidic isoform ARNm (GS2), and, on
the contrary, to an increase of the cytosolic isoform ARNm (GS1). On the other
hand, stimulations were observed for NADH-dependent glutamate synthase, NADH
dependent glutamate dehydrogenase, ARNm quantity of this enzyme, ammonium
accumulation, and protease activity. In parallel, stimulations were observed for
NAD+ and NADP+-dependent malate dehydrogenase and NADP+-dependent isocitrate
dehydrogenase. These results were discussed in relation to the hypothesis
attributing to the dehydrogenase enzymes (GDH, MDH, ICDH) an important role in
the plant defence processes against cadmium-induced stresses.
PMID- 17027641
TI - Dynamical and statistical models of vertebrate population dynamics.
AB - Population dynamics methodology now powerfully combines discrete time models
(with constant parameters, density dependence, random environment, and/or
demographic stochasticity) and capture-recapture models for estimating
demographic parameters. Vertebrate population dynamics has strongly benefited
from this progress: survival estimates have been revised upwards, trade-offs
between life history traits have been demonstrated, analyses of population
viability and management are more and more realistic. Promising developments
concern random effects, multistate and integrated models. Some biological
questions (density dependence, links between individual and population levels,
and diversification of life histories) can now be efficiently attacked.
PMID- 17027642
TI - Relevance of various formulations of phytoplankton chlorophyll a:carbon ratio in
a 3D marine ecosystem model.
AB - Numerous experimental studies showed that the phytoplankton Chla-to-Carbon ratio
(Chla:C) is highly variable, whereas most of the marine ecosystem models use a
constant ratio. In this work, we tested three different formulations for
computing the modelled Chla in a 3D coupled hydrodynamical-biogeochemical model
of the Southwest lagoon of New Caledonia. The first formulation considers a
constant Chla:C ratio. In the second one, Chla is a diagnostic variable related
to the variable phytoplankton nitrogen-to-carbon ratio. In the last formulation,
Chla is a state variable of the model, which is dynamically simulated. Results
showed important differences between the formulations, the first leading to
overestimate the Chla concentration in low nutrients conditions. Thus, this study
strengthens the importance of the Chla modelling in a coupled model in order to
better estimate a crucial variable for validation of ecosystem models.
PMID- 17027643
TI - New proposals for naming lower-ranked taxa within the frame of the International
Code of Zoological Nomenclature.
AB - The recent multiplication of cladistic hypotheses for many zoological groups
poses a challenge to zoological nomenclature following the International Code of
Zoological Nomenclature: in order to account for these hypotheses, we will need
many more ranks than currently allowed in this system, especially in lower
taxonomy (around the ranks genus and species). The current Code allows the use of
as many ranks as necessary in the family-series of nomina (except above
superfamily), but forbids the use of more than a few ranks in the genus and
species-series. It is here argued that this limitation has no theoretical
background, does not respect the freedom of taxonomic thoughts or actions, and is
harmful to zoological taxonomy in two respects at least: (1) it does not allow to
express in detail hypothesized cladistic relationships among taxa at lower
taxonomic levels (genus and species); (2) it does not allow to point
taxonomically to low-level differentiation between populations of the same
species, although this would be useful in some cases for conservation biology
purposes. It is here proposed to modify the rules of the Code in order to allow
use by taxonomists of an indeterminate number of ranks in all nominal-series.
Such an 'expanded nomenclatural system' would be highly flexible and likely to be
easily adapted to any new finding or hypothesis regarding cladistic relationships
between taxa, at genus and species level and below. This system could be useful
for phylogeographic analysis and in conservation biology. In zoological
nomenclature, whereas robustness of nomina is necessary, the same does not hold
for nomenclatural ranks, as the latter are arbitrary and carry no special
biological, evolutionary or other information, except concerning the mutual
relationships between taxa in the taxonomic hierarchy. Compared to the Phylocode
project, the new system is equally unambiguous within the frame of a given
taxonomic frame, but it provides more explicit and informative nomina for non
specialist users, and is more economic in terms of number of nomina needed to
account for a given hierarchy. These ideas are exemplified by a comparative study
of three possible nomenclatures for the taxonomy recently proposed by Hillis and
Wilcox (2005) for American frogs traditionally referred to the genus Rana.
PMID- 17027644
TI - [Laurentaeglyphea, a new genus for the second recent species of Glypheid recently
discovered. (Crustacea Decapoda Glypheidae)].
AB - In 1975, a recent member of a large group of Crustacea Decapoda was described as
Neoglyphea inopinata Forest & de Saint Laurent, until now only known as fossils
and presumed extinct since the Eocene. The only known specimen had been collected
in the Philippine waters, in 1908, at a depth of 200 m. During the next years,
three oceanographical expeditions gave more adult specimens, allowing complete
study of the species. From its morphology, it appeared that the status attributed
to glypheids in the past in the classification of Decapoda Crustacea was quite
erroneous. This group, until then considered as related to Palinurids (rock
lobsters) was in fact much closer to Astacids (lobster, crayfish, etc.). In 1982,
N. inopinata was recorded from the other side of Equator, from the Timor Sea. In
October 2005, a second living species of glypheid was discovered southwest of New
Caledonia. It was named Neoglyphea neocaledonica B. Richer de Forges, 2006.
However, important and significant differences set apart the two species,
especially the ornamentation of the cephalothorax, the conformation of the
cephalic part and the proportions of epistom and thoracic appendages, being much
more robust. It seems justified to establish, for the more recently described
species, a new genus, Laurentaeglyphea, much closer to fossil forms.
PMID- 17027645
TI - Low dose cadmium poisoning results in sustained ERK phosphorylation and caspase
activation.
AB - Cadmium poisoning has been known to result in a wide variety of cellular
responses, including oxidative stress and kinase activation. It has been reported
that ERK is activated following acute cadmium exposure, and this response is
commonly seen as a classical ERK survival mechanism. Here, we analyzed different
cell types for their responses to low concentrations of cadmium poisoning. We
found that there is an association between cell susceptibility to cadmium
toxicity and ERK activation. This activation is atypical, since it consists of a
sustained ERK phosphorylation, that lasts up to 6 days post stimulation. This
activation is associated with the appearance of cleaved caspases 8 and 3,
processed PARP, and irreversible damage. Pharmacological inhibition of ERK
phosphorylation results in the ability of cells to resist cadmium poisoning. Our
data indicate that low cadmium concentrations result in an unconventional ERK
sustained phosphorylation, which in turn leads to death signaling.
PMID- 17027646
TI - Binding of glutamate receptor delta2 to its scaffold protein, Delphilin, is
regulated by PKA.
AB - The glutamate receptor delta2 (GluRdelta2) is selectively expressed in cerebellar
Purkinje cells and plays an important role in motor learning, motor coordination,
and long-term depression. Delphilin is identified as a GluRdelta2-interacting
protein, selectively expressed in Purkinje cell-parallel fiber synapses, and
specifically interacts with the GluRdelta2 C-terminus via its PDZ domain. Here,
surface plasmon resonance analyses showed that Delphilin PDZ bound to GluRdelta2
C-terminal peptide (DPDRGTSI), but not to its phosphopeptides (DPDRGphosphoTSI
and DPDRGTphosphoSI). We showed the incorporation of phosphate into threonine at
2 (-2T) and serine at -1 (-1S) of GluRdelta2 C-terminus by cAMP-dependent protein
kinase (PKA) in vitro. In the experiments using heterologous expression system,
Delphilin coimmunoprecipitated with GluRdelta2 was dramatically decreased under
the condition with forskolin and isobutylmethylxanthine, which led to cAMP
dependent phosphorylation by PKA. Thus, phosphorylation of -2T and/or -1S of
GluRdelta2 C-terminus by PKA may regulate the binding of GluRdelta2 to its
scaffolding protein, Delphilin.
PMID- 17027647
TI - ESE-3 transcription factor is involved in the expression of death receptor (DR)-5
through putative Ets sites.
AB - The death receptor 5 (DR-5), a receptor for tumor necrosis factor-related
apoptosis-inducing ligand (TRAIL), is critical for TRAIL-mediated apoptosis in
various tumor cells. The ESE-3, a member of Ets transcription factors, regulates
the expression of a variety of cellular genes by binding to purine-rich GGAA/T
core sequence in cooperation with other transcription factors and co-factors. In
this study, we demonstrate for the first time that ESE-3 regulates DR-5
expression through Ets binding sequences on the DR-5 promoter. Using a
combination of the electrophoretic mobility shift assay and the luciferase
reporter assay, we identified putative Ets sites responsible for ESE-3
transcriptional activity on the DR-5 promoter. In addition, we show the possible
involvement of co-factors CBP and p300 in ESE-3-mediated DR-5 up-regulation.
PMID- 17027648
TI - The interaction of mammalian Class C Vps with nSec-1/Munc18-a and syntaxin 1A
regulates pre-synaptic release.
AB - Membrane docking and fusion in neurons is a highly regulated process requiring
the participation of a large number of SNAREs (soluble N-ethylmaleimide sensitive
factor attachment protein receptors) and SNARE-interacting proteins. We found
that mammalian Class C Vps protein complex associated specifically with nSec
1/Munc18-a, and syntaxin 1A both in vivo and in vitro. In contrast, VAMP2 and
SNAP-25, other neuronal core complex proteins, did not interact. When co
transfected with the human growth hormone (hGH) reporter gene, mammalian Class C
Vps proteins enhanced Ca2+-dependent exocytosis, which was abolished by the Ca2+
channel blocker nifedipine. In hippocampal primary cultures, the lentivirus
mediated overexpression of hVps18 increased asynchronous spontaneous synaptic
release without changing mEPSCs. These results indicate that mammalian Class C
Vps proteins are involved in the regulation of membrane docking and fusion
through an interaction with neuronal specific SNARE molecules, nSec-1/Munc18-a
and syntaxin 1A.
PMID- 17027649
TI - ErbB-4 and TNF-alpha converting enzyme localization to membrane microdomains.
AB - Sequential proteolytic processing of ErbB-4 occurs in response to ligand
addition. Here, we assess the localization of cleavable and non-cleavable ErbB-4
isoforms to membrane microdomains using three methodologies: (1) Triton X-100
insolubility, (2) Brij98-insolubility, and (3) detergent-free density gradient
centrifugation. Whereas ErbB-4 translocated to a Triton X-100-insoluble fraction
upon treatment of T47D cells with heregulin, it constitutively associated with a
Brij98-insoluble fraction and a lipid raft fraction isolated using detergent-free
methodology. Comparison of cleavable and non-cleavable isoforms of ErbB-4
revealed that both ErbB-4 isoforms are constitutively localized to either a
Triton X-100-soluble or Brij98-insoluble fraction. In contrast, addition of
heregulin resulted in translocation of the cleavable isoform to a detergent-free
lipid raft. Tumor necrosis factor-alpha converting enzyme (TACE), the ectodomain
secretase for ErbB-4, was present predominantly in its mature active form in most
microdomains analyzed. These data suggest the assembly of ErbB-4 ectodomain
cleavage apparatus in a membrane microdomain.
PMID- 17027650
TI - Thrombin induces rapid PAR1-mediated non-classical FGF1 release.
AB - Thrombin induces cell proliferation and migration during vascular injury. We
report that thrombin rapidly stimulated expression and release of the pro
angiogenic polypeptide fibroblast growth factor 1 (FGF1). Thrombin failed to
induce FGF1 release from protease-activated receptor 1 (PAR1) null fibroblasts,
indicating that this effect was dependent on PAR1. Similarly to thrombin, FGF1
expression and release were induced by TRAP, a specific oligopeptide agonist of
PAR1. These results identify a novel aspect of the crosstalk between FGF and
thrombin signaling pathways which both play important roles in tissue repair and
angiogenesis.
PMID- 17027651
TI - Surface functionalization of inorganic nano-crystals with fibronectin and E
cadherin chimera synergistically accelerates trans-gene delivery into embryonic
stem cells.
AB - Stem cells holding great promises in regenerative medicine have the potential to
be differentiated to a specific cell type through genetic manipulation. However,
conventional ways of gene transfer to such progenitor cells suffer from a number
of disadvantages particularly involving safety and efficacy issues. Here, we
report on the development of a bio-functionalized inorganic nano-carrier of DNA
by embedding fibronectin and E-cadherin chimera on the carrier, leading to its
high affinity interactions with embryonic stem cell surface and accelerated trans
gene delivery for subsequent expression. While only apatite nano-particles were
very inefficient in transfecting embryonic stem cells, fibronectin-anchored
particles and to a more significant extent, fibronectin and E-cadherin-Fc
associated particles dramatically enhanced trans-gene delivery with a value
notably higher than that of commercially available lipofection system. The
involvement of both cell surface integrin and E-cadherin in mediating
intracellular localization of the hybrid carrier was verified by blocking
integrin binding site with excess free fibronectin and up-regulating both
integrin and E-cadherin through PKC activation. Thus, the new establishment of a
bio-functional hybrid gene-carrier would promote and facilitate development of
stem cell-based therapy in regenerative medicine.
PMID- 17027652
TI - A high affinity human antibody antagonist of P-selectin mediated rolling.
AB - We have characterized the IgG form of a previously isolated and engineered single
chain Fv (scFv), named RR2r3s4-1, that binds to human PSGL-1. This fully human
IgG was determined to have a Kd of 1.8+/-0.7 nM by fluorescence quenching
titration. It better inhibits P-selectin-PSGL-1 interactions than a commercially
available murine monoclonal antibody KPL1 and better inhibits neutrophil rolling
than KPL1. Thus, RR2r3s4-1 is the most effective antibody at inhibiting P
selectin-PSGL-1 interactions known. Specificity analysis reveals that RR2r3s4-1
does not cross react with murine PSGL-1 and thus requires more than tyrosine
sulfate for binding to human PSGL-1. This evidence demonstrates the therapeutic
potential of this antibody as a potent anti-inflammatory therapeutic.
PMID- 17027653
TI - Treatment of diffuse large B-cell lymphomas.
PMID- 17027654
TI - Diffuse aggressive histologies of non-hodgkin lymphoma: treatment and biology of
limited disease.
AB - A quarter century has passed since the paradigm for treating aggressive
histologies of non-Hodgkin lymphoma (NHL) presenting with limited extent of
disease (LD) changed from using aggressive surgical staging techniques followed
by primary radiotherapy (RT) to clinical staging followed by initial treatment
with doxorubicin-containing chemotherapy (CT). This paradigm shift occurred for
two reasons. First, unlike the predictable contiguous spread of Hodgkin lymphoma
from one lymph node region to the next, the NHLs are largely systemic diseases
characterized by early hematogenous spread. Second, the discovery of a potential
curative combination of drugs, including cyclophosphamide, doxorubicin,
vincristine, and prednisone (CHOP), for use in advanced disease could eradicate
micro-metastatic disease in patients with LD. The focus of current investigation
on controlling the systemic nature of the disease has not changed. In this
regard, new effective systemic therapies using combination chemotherapy plus
monoclonal antibodies have resulted in improved outcome for patients with
advanced disease and those treatment strategies are now under investigation in
patients with LD.
PMID- 17027655
TI - Standard treatment of advanced-stage diffuse large B-cell lymphoma.
AB - Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma and is not
localized in 70% of the cases. Even if the clinical picture, the morphologic
aspect, and the prognostic parameters are different from one patient to another,
the standard treatment is the same for all patients. Currently, treatment
decision is based on the International Prognostic Index (IPI) and age of the
patient. Outcome has been completely modified with the introduction of rituximab
in combination with chemotherapy. A review of standard treatment and remaining
questions is presented.
PMID- 17027656
TI - Dose-intensified treatment of advanced-stage diffuse large B-cell lymphomas.
AB - The introduction of the CHOP (cyclophosphamide, doxorubicin, vincristine, and
prednisone) regimen 30 years ago was the great breakthrough in the treatment of
advanced-stage aggressive lymphomas. About 50% of all patients treated with CHOP
achieved complete remission, and about one third experienced long-term disease
free survival and cure. Attempts to improve results by modifications of CHOP
using escalated doses, additional drugs, or the alternative use of putatively non
cross-resistant chemotherapy regimens were not confirmed in randomized trials.
With the availability of granulocyte colony-stimulating factor (G-CSF) and the
tool of autologous stem cell support in the 1990s, dose escalation, dose
densification (by interval reduction), or combinations thereof were pursued to
increase dose intensity. While dose-escalation strategies, including high-dose
approaches necessitating stem cell support, have not been demonstrated
unequivocally yet to be superior to a baseline CHOP-21, dose-dense (biweekly)
modifications improved the outcome of young and elderly patients with aggressive
lymphomas compared to baseline CHOP-21. The challenges in the era of the
monoclonal antibody rituximab are the identification of the ideal chemotherapy
partner for rituximab both with respect to potential synergistic effects and to
the lack of interference with its effector mechanisms. Finally, the issue of
intensifying rituximab within such approaches must be addressed by appropriately
designed randomized trials.
PMID- 17027657
TI - Drug resistance in diffuse large B-cell lymphoma.
AB - Despite significant advances in the treatment of diffuse large B-cell lymphoma
(DLBCL), drug resistance remains a major cause of treatment failure. Early
strategies to improve outcome were mostly empiric or relied on classical
mechanisms of drug resistance and were largely unsuccessful. More recent
approaches have been aided by an understanding of the molecular pharmacology of
drug action and tumor biology. Microarray profiling in particular has provided
important insights into the complex biology of DLBCL and has led to a molecular
taxonomy based on cell of origin and pathways of lymphomagenesis. It is now
recognized that drug resistance is a complex and dynamic process related to cell
cycle and apoptotic pathways, cellular differentiation, and the microenvironment.
Drugs that target potential pathways of drug resistance, such as nuclear factor
kappaB (NFkappaB), cyclin-dependent kinases (CDKs), and BCL-2 have entered
clinical trials. However, the complexity of drug resistance requires that future
clinical trials incorporate molecular translational endpoints to help identify
the biologic basis of treatment failure.
PMID- 17027658
TI - Role of hematopoietic stem cell transplantation for advanced-stage diffuse large
cell B-cell lymphoma-B.
AB - The prognosis of patients with relapsed or refractory diffuse large cell B-cell
lymphoma-B (DLCL-B) is poor with conventional salvage chemotherapy; therefore,
high-dose therapy (HDT) combined with autologous stem cell transplant (ASCT) has
become the treatment of choice for these patients. The outcomes of transplant are
better in patients with chemosensitive relapse: those with a longer duration of
first remission (>12 month) and those with an age-adjusted low-risk International
Prognostic Index (IPI) at relapse. Several high-dose regimens with or without
total body irradiation (TBI) have been used with similar outcomes. Relapse
remains the most common cause of treatment failure, and thus the use of
radioimmunotherapy (RIT) in the high-dose regimens and incorporation of rituximab
in the transplant setting have been explored. Several studies have shown that RIT
both at conventional dose and at high dose can be given in combination with high
dose chemotherapy regimens without additional toxicity or delay in hematopoietic
recovery after ASCT. Additional studies using RIT in combination with high-dose
chemotherapy and ASCT are ongoing, and preliminary results suggest that these
approaches may be superior to conventional high-dose regimens. Since rituximab is
an effective therapy for B-cell non-Hodgkin's lymphoma and given its limited
toxicity, rituximab has been incorporated into HDT and ASCT for DLCL-B as in vivo
purging, as part of high-dose regimens, and as maintenance therapy to prevent
relapse. Preliminary results suggested that rituximab during ASCT and as
maintenance therapy post-transplant reduces the risk of relapse and improves
survival; however, these results need to be confirmed in phase III randomized
trials. The role of ASCT during first remission as consolidative therapy in
patients with DLCL-B remains controversial and should not be performed outside of
the clinical trial setting. Allogeneic stem cell transplant (allo-SCT) for
patients with relapsed DLCL-B is associated with significant toxicity and should
be reserved for patients who relapse after ASCT or those with persistent marrow
involvement. Innovative approaches are needed for primary refractory and
chemoresistant relapsed DLCL-B since these patients have very poor outcomes after
ASCT.
PMID- 17027659
TI - New drugs for the treatment of advanced-stage diffuse large cell lymphomas.
AB - The rapid pace of discovering new signaling pathways that influence the growth
and survival of different types of cancer cells has produced a daunting array of
potentially new, "drugable" targets for the treatment of cancer. This has been
particularly true for the lymphomas. The empiric observation that many kinds of
"novel targeted" drugs appear to exhibit relatively selective patterns of
activity is testament to the concept that the lymphomas represent an incredibly
diverse group of human cancers. Targeting one pathway in a subtype of lymphoma
may not be universally effective against all subtypes of lymphoma, even closely
related ones. These observations suggest that pharmacologically driven "target
identification" plays an important role in the continued development of new
therapeutic agents, and underscores the need for more research into the biologic
basis for different subtypes of lymphoma. Over the past 10 years, there has been
an explosion of new drugs making their way through preclinical laboratories and
early clinical studies. These experiences have taught us some frustrating
lessons. Sometimes, the strongest biologic rationale is associated with the
poorest clinical results. Sometimes, where no rationale exists, golden
therapeutic opportunities emerge. In either case, both experiences typically end
up teaching us something about the disease we didn't historically appreciate. In
this review, we will take a close look at some of the more intriguing targets in
aggressive large B-cell lymphomas, all of which now have small molecules that can
profoundly affect their activity, activity we hope will lead to new treatment
opportunities. We will focus on the biologic rationale for targeting novel
pathways regulated by Bcl-6, Bcl-2, BLysS, and APRIL for example. In addition, we
will review how new concepts in structural biology and chemical design can help
produce new generation compounds with novel activity, as is the case for
pralatrexate and targeting the reduced folate carrier-type-1. Clearly, given the
breadth and depth of information emerging on these and other relevant biologic
pathways, we are limited to discussing only a few illustrative examples, which
should in no way detract from the importance of other critical signaling and
survival pathways now being exploited in the treatment of lymphoma.
PMID- 17027670
TI - Tyramine in the assessment of regional adrenergic function.
AB - Regional adrenergic function is difficult to assess in humans. Tyramine given
through a microdialysis probe may be a useful tool in this regard. However,
tyramine data is hard to interpret given the drug's complex mode of action. We
characterized the response to tyramine, isoproterenol, and dopamine in adipose
tissue with microdialysis probes in normal subjects. We measured glycerol
concentrations to follow changes in lipolysis and monitored tissue perfusion with
ethanol dilution. During perfusion with tyramine, dialysate glycerol
concentration increased dose-dependently from 83+/-8 microM at baseline to 181+/
18 microM at 3.5 mM tyramine (p<0.001) followed by a fall down to 121+/-9 microM
at 35 mM tyramine (p<0.001). Propranolol almost completely blocked this response.
A similar lipolytic response was not observed in isolated human adipocytes.
Dopamine <35 microM did not replicate the tyramine-induced lipolysis; however,
dopamine >35 microM potently inhibited lipolysis. We conclude that tyramine
induced lipolysis is explained by a pre-synaptic mechanism. Tyramine applied
through a microdialysis probe in concentrations up to 3.5 mM can be used to
assess pre- and post-synaptic mechanisms regulating lipid mobilization.
PMID- 17027671
TI - Modulation of extracellular matrix components by metalloproteinases and their
tissue inhibitors during degeneration and regeneration of rat sural nerve.
AB - The success of peripheral nervous system regeneration has been associated with
changes on the microenvironment, particularly on the extracellular matrix (ECM)
components. In the present study we analyzed by indirect immunohistochemistry,
electron microscopy and Western blotting, the distribution of ECM components,
metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), during Wallerian
degeneration (WD) and nerve regeneration (2nd, 7th and 21st days after injury) on
crushed rat sural nerves. Our results showed that laminin alpha3-chain and alpha2
chain are over expressed during the early stages of degeneration and regeneration
respectively, whereas type IV collagen expression increased progressively after
crush. On the other hand, the expression of chondroitin sulfate was down
regulated during the early stages of degeneration, returning progressively to
normal values during nerve regeneration. The expression of MMP-3 was almost
normal immediately after lesion, and then reduced progressively achieving the
smallest expression at 21 days after crush; on the contrary, the expression of
MMP-7 increased significantly immediately after crush (2nd day) returning to
normal values afterwards. TIMP-1 and TIMP-2 were over expressed at the beginning
of WD, returning progressively to normal values after that. These results
indicate that the modifications of ECM components, which are favorable for nerve
regeneration, are correlated with changes on the balance between MMPs and TIMPs.
PMID- 17027672
TI - Combining motor training with transplantation of rat bone marrow stromal cells
does not improve repair or recovery in rats with thoracic contusion injuries.
AB - Previous studies have demonstrated that either transplantation of bone marrow
stromal cells (MSC) or physical exercise regimens can elicit limited functional
recovery following spinal cord injury, presumably through different mechanisms.
The present study examined whether transplantation of MSC derived from transgenic
Fischer alkaline phosphatase (AP) rats, in combination with exercise, would have
synergistic effects leading to recovery of function that is greater than either
alone. Adult female Sprague-Dawley rats received a moderate thoracic contusion
injury and were divided into three groups: operated controls (Op-Control), MSC
transplant recipients (MSC), and MSC transplant recipients plus exercise
(MSC+Ex). Nine days after contusion, a Vitrogen matrix +/-one million MSC was
injected into the lesion site in all animals. Immunosuppression with high doses
of Cyclosporine A, required for MSC survival, was provided for all animals.
Passive hindlimb exercise on motorized bicycles was applied 1 h/day, 3 days/week
to the MSC+Ex group. A battery of behavioral tests was performed weekly to assess
motor and sensory functions in all 3 groups for 12 weeks. Morphological
evaluation included MSC survival, evidence of axonal growth into grafts,
phenotypic analysis of MSC, and lesion/transplant size. The weight of the medial
gastrocnemius muscle, a hindlimb muscle activated during stance, was used to
identify extent of atrophy. No differences in motor recovery were found among the
three groups. MSC survived 3 months after transplantation, indicating that the
immunosuppression treatment was successful. The extent of survival was variable,
and there was no correlation between MSC survival and behavioral scores. The
matrix persisted, filling the lesion cavity, and some axons grew into the
lesion/matrix but to a similar extent in all groups. There was no difference in
lesion/matrix size among groups, indicating no neuroprotective effect on the host
provided by the treatments. Immunocytochemical analysis provided no evidence that
MSC differentiated into neurons, astrocytes or oligodendrocytes. Muscle mass of
the medial gastrocnemius was diminished in the Op-Control group indicating
significant atrophy, but was partially preserved in both the MSC and MSC+Ex
groups. Our results indicate that combining the beneficial effects of rat MSC and
this exercise protocol was not sufficient to enhance behavioral recovery.
PMID- 17027673
TI - The relationship between electrophysiological correlates of recollection and
amount of information retrieved.
AB - The electrophysiological correlates of recollection were investigated with a
modified Remember/Know task in which subjects signaled whether they fully or
partially recollected visual object information in each study episode. A positive
going ERP deflection--the left parietal old/new effect--was sensitive to the
amount of information recollected, demonstrating greater amplitude when elicited
by test items associated with full relative to partial recollection. These
findings support prior proposals that the left parietal ERP old/new effect is
sensitive to the amount of information recollected from episodic memory. An early
onsetting (ca. 150 ms), left frontal old/new effect differentiated items accorded
correct old versus correct new responses regardless of whether the items were
endorsed as familiar or recollected. This finding extends the range of
circumstances under which early, frontally distributed old/new effects occur, and
adds weight to previous suggestions that these effects are a neural correlate of
familiarity-driven recognition memory.
PMID- 17027674
TI - G-protein coupled receptor kinase-like immunoreactivity in the snail, Helix
pomatia, neurons.
AB - GPRCs are regulated via phosphorylation by different protein kinases including
GRKs and PKA and PKC. The purpose of this study was to determine the presence and
physiological role of GRKs in the tissues of the snail, Helix pomatia. Here we
report that immunoblotting of brain homogenate with anti-GRK2/3 antibody prepared
from mammalian tissue can be detected in snail GRK-like immunoreactivity. The
GRK2/3 immunoreactivity was found at approximately 80 kDa in a variety of cells,
including salivary duct, salivary gland and eye. Intracellular injection of the
anti-GRK2/3 prevented the neuron from desensitization and agonist-induced
activation augmented the phosphorylated GRKs in the membrane fraction suggesting
that GRKs may have a functional role in the neuropeptide receptor desensitization
in snail.
PMID- 17027676
TI - Wild plants and viruses: under-investigated ecosystems.
PMID- 17027677
TI - Genetic diversity of plant virus populations: towards hypothesis testing in
molecular epidemiology.
PMID- 17027678
TI - Plant virus epidemiology: the concept of host genetic vulnerability.
PMID- 17027679
TI - History and current distribution of begomoviruses in Latin America.
PMID- 17027680
TI - Evolutionary epidemiology of plant virus disease.
PMID- 17027681
TI - Control of plant virus diseases.
PMID- 17027682
TI - Control of tropical plant virus diseases.
PMID- 17027683
TI - Begomovirus evolution and disease management.
PMID- 17027684
TI - Transgenic papaya: development, release, impact and challenges.
PMID- 17027685
TI - Cassava mosaic virus disease in East and Central Africa: epidemiology and
management of a regional pandemic.
PMID- 17027686
TI - Host-plant viral infection effects on arthropod-vector population growth,
development and behaviour: management and epidemiological implications.
PMID- 17027687
TI - The migration of insect vectors of plant and animal viruses.
PMID- 17027689
TI - Tissue preparation and banking.
AB - With the increasing application of genomic and proteomic technologies to the
research of neurological and psychiatric disorders it has become imperative that
the postmortem tissue utilized be of the highest quality possible. Every step of
the research design, from identifying donors, acquiring sufficient information
for accurate diagnosis, to assessing tissue quality has to be carefully
considered. In order to obtain high-quality RNA and protein from the postmortem
brain tissue a standardized system of brain collection, dissection, and storage
must be employed and key ante- and postmortem factors must be considered.
Reliable RNA expression and protein data can be obtained from postmortem brains
with relatively long postmortem intervals (PMIs) if the agonal factors and
acidosis are not severe. While pH values are correlated with RNA integrity number
(RIN), a higher pH does not guarantee intact RNA. Consequently RNA integrity must
be assessed for every case before it is included in a study. An analysis of anti-
and postmortem factors in a large brain collection has revealed that several
diagnostic groups have significantly lower pH values than other groups, however,
they do not have significantly lower RIN values. Moreover, the lower pH of these
groups is not entirely due to agonal factors and/or smoking, indicating that
these subjects may have additional metabolic abnormalities that contribute to the
lower pH values.
PMID- 17027690
TI - Functional genomic methodologies.
AB - The ability to form tenable hypotheses regarding the neurobiological basis of
normative functions as well as mechanisms underlying neurodegenerative and
neuropsychiatric disorders is often limited by the highly complex brain circuitry
and the cellular and molecular mosaics therein. The brain is an intricate
structure with heterogeneous neuronal and nonneuronal cell populations dispersed
throughout the central nervous system. Varied and diverse brain functions are
mediated through gene expression, and ultimately protein expression, within these
cell types and interconnected circuits. Large-scale high-throughput analysis of
gene expression in brain regions and individual cell populations using modern
functional genomics technologies has enabled the simultaneous quantitative
assessment of dozens to hundreds to thousands of genes. Technical and
experimental advances in the accession of tissues, RNA amplification
technologies, and the refinement of downstream genetic methodologies including
microarray analysis and real-time quantitative PCR have generated a wellspring of
informative studies pertinent to understanding brain structure and function. In
this review, we outline the advantages as well as some of the potential
challenges of applying high throughput functional genomics technologies toward a
better understanding of brain tissues and diseases using animal models as well as
human postmortem tissues.
PMID- 17027691
TI - Methods for proteomics in neuroscience.
AB - Proteomics reveals complex protein expression, function, interactions and
localization in different phenotypes of neuron. As proteomics, regarded as a
highly complex screening technology, moves from a theoretical approach to
practical reality, neuroscientists have to determine the most-appropriate
applications for this technology. Even though proteomics compliments genomics, it
is in sheer contrast to the basically constant genome due to its dynamic nature.
Neuroscientists have to surmount difficulties particular to the research in
neuroscience; such as limited sample amounts, heterogeneous cellular compositions
in samples and the fact that many proteins of interest are hydrophobic proteins.
The necessity of exclusive technology, sophisticated software and skilled
manpower tops the challenge. This review examines subcellular organelle
isolation, protein fractionation and separation using two-dimensional gel
electrophoresis (2-DGE) as well as multi-dimensional liquid chromatography (LC)
followed by mass spectrometry (MS). The methods for quantifying relative gene
product expression between samples (e.g., two-dimensional difference in gel
electrophoresis (2D-DIGE), isotope-coded affinity tag (ICAT) and iTRAQ) are
elaborated. An overview of the techniques used currently to assign post
translational modification status on a proteomics scale is also evaluated. The
feasible coverage of the proteome, ability to detect unique cell components such
as post-synaptic densities and membrane proteins, resource requirements and
quantitative as well as qualitative reliability of different approaches is also
discussed. While there are many challenges in neuroproteomics, this field
promises many returns in the future.
PMID- 17027692
TI - Functional genomics and proteomics in the clinical neurosciences: data mining and
bioinformatics.
AB - The goal of this chapter is to introduce some of the available computational
methods for expression analysis. Genomic and proteomic experimental techniques
are briefly discussed to help the reader understand these methods and results
better in context with the biological significance. Furthermore, a case study is
presented that will illustrate the use of these analytical methods to extract
significant biomarkers from high-throughput microarray data. Genomic and
proteomic data analysis is essential for understanding the underlying factors
that are involved in human disease. Currently, such experimental data are
generally obtained by high-throughput microarray or mass spectrometry
technologies among others. The sheer amount of raw data obtained using these
methods warrants specialized computational methods for data analysis. Biomarker
discovery for neurological diagnosis and prognosis is one such example. By
extracting significant genomic and proteomic biomarkers in controlled
experiments, we come closer to understanding how biological mechanisms contribute
to neural degenerative diseases such as Alzheimers' and how drug treatments
interact with the nervous system. In the biomarker discovery process, there are
several computational methods that must be carefully considered to accurately
analyze genomic or proteomic data. These methods include quality control,
clustering, classification, feature ranking, and validation. Data quality control
and normalization methods reduce technical variability and ensure that discovered
biomarkers are statistically significant. Preprocessing steps must be carefully
selected since they may adversely affect the results of the following expression
analysis steps, which generally fall into two categories: unsupervised and
supervised. Unsupervised or clustering methods can be used to group similar
genomic or proteomic profiles and therefore can elucidate relationships within
sample groups. These methods can also assign biomarkers to sub-groups based on
their expression profiles across patient samples. Although clustering is useful
for exploratory analysis, it is limited due to its inability to incorporate
expert knowledge. On the other hand, classification and feature ranking are
supervised, knowledge-based machine learning methods that estimate the
distribution of biological expression data and, in doing so, can extract
important information about these experiments. Classification is closely coupled
with feature ranking, which is essentially a data reduction method that uses
classification error estimation or other statistical tests to score features.
Biomarkers can subsequently be extracted by eliminating insignificantly ranked
features. These analytical methods may be equally applied to genetic and
proteomic data. However, because of both biological differences between the data
sources and technical differences between the experimental methods used to obtain
these data, it is important to have a firm understanding of the data sources and
experimental methods. At the same time, regardless of the data quality, it is
inevitable that some discovered biomarkers are false positives. Thus, it is
important to validate discovered biomarkers. The validation process may be slow;
yet, the overall biomarker discovery process is significantly accelerated due to
initial feature ranking and data reduction steps. Information obtained from the
validation process may also be used to refine data analysis procedures for future
iteration. Biomarker validation may be performed in a number of ways - bench-side
in traditional labs, web-based electronic resources such as gene ontology and
literature databases, and clinical trials.
PMID- 17027693
TI - Reproducibility of microarray studies: concordance of current analysis methods.
PMID- 17027694
TI - The genomics of mood disorders.
PMID- 17027695
TI - Transcriptome alterations in schizophrenia: disturbing the functional
architecture of the dorsolateral prefrontal cortex.
AB - The availability of methods for quantifying tissue concentrations of messenger
RNAs in the postmortem of the human brain has provided a number of new findings
in schizophrenia. However, understanding how these findings actually relate to
the disease process of schizophrenia requires knowledge both of the factors that
might give rise to such changes in gene expression and of the impact of these
changes on the function of the affected neural circuits. Consequently, this
chapter provides a review of the potential causes and consequences of some of the
schizophrenia-related transcriptome changes in the dorsolateral prefrontal
cortex, a brain region implicated in the pathophysiology of certain core
cognitive deficits in this illness.
PMID- 17027696
TI - Strategies for improving sensitivity of gene expression profiling: regulation of
apoptosis in the limbic lobe of schizophrenics and bipolars.
PMID- 17027698
TI - Neuronal gene expression profiling: uncovering the molecular biology of
neurodegenerative disease.
AB - The development of gene array techniques to quantify expression levels of dozens
to thousands of genes simultaneously within selected tissue samples from control
and diseased brain has enabled researchers to generate expression profiles of
vulnerable neuronal populations in several neurodegenerative diseases, including
Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, and
Creutzfeld-Jakob disease. Intriguingly, gene expression analysis reveals that
vulnerable brain regions in many of these diseases share putative pathogenetic
alterations in common classes of genes, including decrements in synaptic
transcript levels and increments in immune response transcripts. Thus, gene
expression profiles of diseased neuronal populations may reveal mechanistic clues
to the molecular pathogenesis underlying various neurological diseases and aid in
identifying potential therapeutic targets. This chapter will review how regional
and single cell gene array technologies have advanced our understanding of the
genetics of human neurological disease.
PMID- 17027697
TI - Assessment of genome and proteome profiles in cocaine abuse.
AB - Until recently, knowledge of the impact of abuse drugs on gene and protein
expression in the brain was limited to less than 100 targets. With the advent of
high-throughput genomic and proteomic techniques investigators are now able to
evaluate changes across the entire genome and across thousands of proteins in
defined brain regions and generate expression profiles of vulnerable
neuroanatomical substrates in rodent and non-human primate drug abuse models and
in human post-mortem brain tissue from drug abuse victims. The availability of
gene and protein expression profiles will continue to expand our understanding of
the short- and long-term consequences of drug addiction and other addictive
disorders and may provide new approaches or new targets for pharmacotherapeutic
intervention. This chapter will review gene expression data from rodent, non
human primate and human post-mortem studies of cocaine abuse and will provide a
preliminary proteomic profile of human cocaine abuse and explore how these
studies have advanced our understanding of addiction.
PMID- 17027699
TI - Epileptogenesis-related genes revisited.
AB - The main goal of this study was to identify common features in the molecular
response to epileptogenic stimuli across different animal models of
epileptogenesis. Therefore, we compared the currently available literature on the
global analysis of gene expression following epileptogenic insult to search for
(i) highly represented functional gene classes (GO terms) within data sets, and
(ii) individual genes that appear in several data sets, and therefore, might be
of particular importance for the development of epilepsy due to different
etiologies. We focused on two well-described models of brain insult that induce
the development of spontaneous seizures in experimental animals: status
epilepticus and traumatic brain injury. Additionally, a few papers describing
gene expression in rat and human epileptic tissue were included for comparison.
Our analysis revealed that epileptogenic insults induce significant changes in
gene expression within a subset of pre-defined GO terms, that is, in groups of
functionally linked genes. We also found individual genes for which expression
changed across different models of epileptogenesis. Alterations in gene
expression appear time-specific and underlie a number of processes that are
linked with epileptogenesis, such as cell death and survival, neuronal
plasticity, or immune response. Particularly, our analysis highlighted
alterations in gene expression in glial cells as well as in genes involved in the
immune response, which suggests the importance of gliosis and immune reaction in
epileptogenesis.
PMID- 17027700
TI - Functional genomics of sex hormone-dependent neuroendocrine systems: specific and
generalized actions in the CNS.
AB - Sex hormone effects on hypothalamic neurons have been worked out to a point where
receptor mechanisms are relatively well understood, a neural circuit for a sex
steroid-dependent behavior has been determined, and several functional genomic
regulations have been discovered and conceptualized. With that knowledge in hand,
we approach deeper problems of explaining sexual arousal and generalized CNS
arousal. After a brief summary of arousal mechanisms, we focus on three chemical
systems which signal generalized arousal and impact hormone-dependent
hypothalamic neurons of behavioral importance: histamine, norepinephrine and
enkephalin.
PMID- 17027701
TI - Implications for the practice of psychiatry.
PMID- 17027702
TI - Human brain evolution.
PMID- 17027703
TI - N-acetylgalactosamine-6-sulfatase protein detection in MPS IVA patient and
unaffected control samples.
AB - BACKGROUND: Mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome) is a
lysosomal storage disorder caused by a deficiency in the activity of the
lysosomal hydrolase N-acetylgalactosamine-6-sulfatase (GALNS). MPS IVA patients
can present with severe myelopathy, hearing loss, heart valve involvement, short
trunk/dwarfism and corneal clouding. Early diagnosis of MPS IVA will allow
potential treatments to be implemented before the onset of irreversible
pathology. METHODS: We have developed a sensitive immune-quantification assay for
the accurate detection of GALNS protein in skin fibroblasts, blood and plasma
from unaffected control and MPS IVA patients. RESULTS: MPS IVA patient fibroblast
extracts (n=11) had non-detectable (ND)-10 ng/mg of 6-sulfatase protein compared
to 3-82 ng/mg for normal controls (n=19). Dried blood-spots from MPS IVA patients
(n=4) contained ND-1.3 ng/L of 6-sulfatase protein compared to 18-145 ng/L for
normal controls (n=49). Plasma from MPS IVA patients (n=7) contained ND 6
sulfatase protein compared to 1-9 ng/L for normal controls (n=49). CONCLUSIONS:
The immune assay described here had the capacity to accurately measure the amount
of GALNS protein in various biological samples, providing the basis of an assay
that could be further developed to enable newborn and high-risk population
screening for MPS IVA patients.
PMID- 17027704
TI - Institute of Medicine urges reforms at FDA.
PMID- 17027705
TI - Should HPV vaccines be mandatory for all adolescents?
PMID- 17027706
TI - Water and sanitation: the neglected health MDG.
PMID- 17027707
TI - The next Director-General of WHO.
PMID- 17027708
TI - SPACE: not the final frontier.
PMID- 17027709
TI - Misoprostol for preventing PPH: some lessons learned.
PMID- 17027710
TI - Glucose lowering and diabetes prevention: are they the same?
PMID- 17027711
TI - The definition of disability: what is in a name?
PMID- 17027712
TI - Rising to the global challenge of the chronic disease epidemic.
PMID- 17027713
TI - Institutional reviews and innovation in clinical research.
PMID- 17027715
TI - Lawrence K Altman.
PMID- 17027716
TI - Are statins analogues of vitamin D?
PMID- 17027717
TI - Are statins analogues of vitamin D?
PMID- 17027718
TI - Are statins analogues of vitamin D?
PMID- 17027719
TI - Are statins analogues of vitamin D?
PMID- 17027720
TI - Smoking and age-related maculopathies.
PMID- 17027721
TI - Treatment of age-related macular degeneration.
PMID- 17027723
TI - Toronto AIDS conference: where were the children?
PMID- 17027724
TI - Cautious optimism for new HIV/AIDS prevention strategies.
PMID- 17027725
TI - Killer fentanyl: a lesson from anaesthesiology.
PMID- 17027726
TI - Confusion begets confusion.
PMID- 17027727
TI - Bad sex.
PMID- 17027729
TI - 30 day results from the SPACE trial of stent-protected angioplasty versus carotid
endarterectomy in symptomatic patients: a randomised non-inferiority trial.
AB - BACKGROUND: Carotid endarterectomy is effective in stroke prevention for patients
with severe symptomatic carotid-artery stenosis, and carotid-artery stenting has
been widely used as alternative treatment. Since equivalence or superiority has
not been convincingly shown for either treatment, we aimed to compare the two.
METHODS: 1200 patients with symptomatic carotid-artery stenosis were randomly
assigned within 180 days of transient ischaemic attack or moderate stroke
(modified Rankin scale score of < or =3) carotid-artery stenting (n=605) or
carotid endarterectomy (n=595). The primary endpoint of this hospital-based study
was ipsilateral ischaemic stroke or death from time of randomisation to 30 days
after the procedure. The non-inferiority margin was defined as less than 2.5% on
the basis of an expected event rate of 5%. Analyses were on an intention-to-treat
basis. This trial is registered at Current Controlled Trials with the
international standard randomised controlled trial number ISRCTN57874028.
FINDINGS: 1183 patients were included in the analysis. The rate of death or
ipsilateral ischaemic stroke from randomisation to 30 days after the procedure
was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy
(absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for
non-inferiority is 0.09. INTERPRETATION: SPACE failed to prove non-inferiority of
carotid-artery stenting compared with carotid endarterectomy for the
periprocedural complication rate. The results of this trial do not justify the
widespread use in the short-term of carotid-artery stenting for treatment of
carotid-artery stenoses. Results at 6-24 months are awaited.
PMID- 17027730
TI - Oral misoprostol in preventing postpartum haemorrhage in resource-poor
communities: a randomised controlled trial.
AB - BACKGROUND: Postpartum haemorrhage is a major cause of maternal mortality in the
developing world. Although effective methods for prevention and treatment of such
haemorrhage exist--such as the uterotonic drug oxytocin--most are not feasible in
resource-poor settings where many births occur at home. We aimed to investigate
whether oral misoprostol, a potential alternative to oxytocin, could prevent
postpartum haemorrhage in a community home-birth setting. METHODS: In a placebo
controlled trial undertaken between September, 2002, and December, 2005, 1620
women in rural India were randomised to receive oral misoprostol (n=812) or
placebo (n=808) after delivery. 25 auxiliary nurse midwives undertook the
deliveries, administered the study drug, and measured blood loss. The primary
outcome was the incidence of acute postpartum haemorrhage (defined as > or =500
mL bleeding) within 2 h of delivery. Analysis was by intention-to-treat. The
trial was registered with the US clinical trials database (http://www.
clinicaltrials.gov) as number NCT00097123. FINDINGS: Oral misoprostol was
associated with a significant reduction in the rate of acute postpartum
haemorrhage (12.0% to 6.4%, p<0.0001; relative risk 0.53 [95% CI 0.39-0.74]) and
acute severe postpartum haemorrhage (1.2% to 0.2%, p<0.0001; 0.20 [0.04-0.91].
One case of postpartum haemorrhage was prevented for every 18 women treated.
Misoprostol was also associated with a decrease in mean postpartum blood loss
(262.3 mL to 214.3 mL, p<0.0001). Postpartum haemorrhage rates fell over time in
both groups but remained significantly higher in the placebo group. Women taking
misoprostol had a higher rate of transitory symptoms of chills and fever than the
control. INTERPRETATION: Oral misoprostol was associated with significant
decreases in the rate of acute postpartum haemorrhage and mean blood loss. The
drug's low cost, ease of administration, stability, and a positive safety profile
make it a good option in resource-poor settings.
PMID- 17027731
TI - Short-term risk of AIDS or death in people infected with HIV-1 before
antiretroviral therapy in South Africa: a longitudinal study.
AB - BACKGROUND: In sub-Saharan Africa, data for short-term risk of AIDS or death,
which might inform decisions about when to start antiretroviral therapy (ART),
are scarce. Our aim was to investigate these risks in patients who had no access
to ART or who were given zidovudine alone. METHODS: 6-month risks (%) of death,
AIDS, and combined risk of AIDS and death (AIDS/death) were calculated according
to CD4-cell count category of less than 200 cells per microL, 200-350 cells per
microL, or greater than 350 cells per microL, stratified by WHO clinical stages 1
and 2 combined, 3, or 4 in untreated patients (n=1399) seeking care in tertiary
public-sector HIV clinics before widespread availability of ART in Cape Town,
South Africa. FINDINGS: Risk of death for WHO stages 1 and 2 was 3.5% for those
with less than 200 cells per microL, 2.8% for 200-350 cells per microL, and 1.2%
for greater than 350 cells per microL. The corresponding rates for WHO stage 3
were 10.8%, 4.3%, and 4.9% and for stage 4, 22.2%, 10.3%, and 13.8%. 52% (90) of
deaths took place in patients without AIDS. 6-month risk of AIDS for WHO stages 1
and 2 was 3.5% for those with less than 200 cells per microL, 1.6% for 200-350
cells per microL, and zero for greater than 350 cells per microL. The
corresponding rates for those with WHO stage 3 disease were 17.4%, 7.0%, and
2.2%. INTERPRETATION: In this study, risk of AIDS in patients with a CD4-cell
count of less than 200 cells per microL or greater than 350 cells per microL was
similar to that previously reported from European cohorts, but was 1.9 times
greater for those with CD4-cell counts of between 200 and 350 cells per microL.
The high death rate before development of AIDS and a high risk of AIDS in those
with CD4-cell counts of 200-350 cells per microL indicate that delay in
initiation of ART is associated with increased morbidity and mortality. These
findings might help to amend criteria for start of ART in resource-limited
settings.
PMID- 17027732
TI - Prevalence of intimate partner violence: findings from the WHO multi-country
study on women's health and domestic violence.
AB - BACKGROUND: Violence against women is a serious human rights abuse and public
health issue. Despite growing evidence of the size of the problem, current
evidence comes largely from industrialised settings, and methodological
differences limit the extent to which comparisons can be made between studies. We
aimed to estimate the extent of physical and sexual intimate partner violence
against women in 15 sites in ten countries: Bangladesh, Brazil, Ethiopia, Japan,
Namibia, Peru, Samoa, Serbia and Montenegro, Thailand, and the United Republic of
Tanzania. METHODS: Standardised population-based household surveys were done
between 2000 and 2003. Women aged 15-49 years were interviewed and those who had
ever had a male partner were asked in private about their experiences of
physically and sexually violent and emotionally abusive acts. FINDINGS: 24,097
women completed interviews, with around 1500 interviews per site. The reported
lifetime prevalence of physical or sexual partner violence, or both, varied from
15% to 71%, with two sites having a prevalence of less than 25%, seven between
25% and 50%, and six between 50% and 75%. Between 4% and 54% of respondents
reported physical or sexual partner violence, or both, in the past year. Men who
were more controlling were more likely to be violent against their partners. In
all but one setting women were at far greater risk of physical or sexual violence
by a partner than from violence by other people. INTERPRETATION: The findings
confirm that physical and sexual partner violence against women is widespread.
The variation in prevalence within and between settings highlights that this
violence in not inevitable, and must be addressed.
PMID- 17027733
TI - Persistent left superior vena cava into left atrium.
PMID- 17027734
TI - Necrotising enterocolitis.
AB - Necrotising enterocolitis is one of the most common gastrointestinal emergencies
in newborn infants. Here we review the epidemiology, clinical presentation, and
pathophysiology of the disease, as well as strategies for diagnosis, management,
and prevention. Necrotising enterocolitis is one of the most devastating and
unpredictable diseases affecting premature infants. Despite decades of research,
its pathogenesis remains unclear; diagnosis can be difficult; and treatment is
challenging. We will need to improve our understanding of intestinal defences in
premature infants, dietary and bacterial factors, and genetic effects that could
predispose infants to necrotising enterocolitis before we can develop new
strategies for prevention and treatment.
PMID- 17027735
TI - Strategies for reducing maternal mortality: getting on with what works.
AB - The concept of knowing what works in terms of reducing maternal mortality is
complicated by a huge diversity of country contexts and of determinants of
maternal health. Here we aim to show that, despite this complexity, only a few
strategic choices need to be made to reduce maternal mortality. We begin by
presenting the logic that informs our strategic choices. This logic suggests that
implementation of an effective intrapartum-care strategy is an overwhelming
priority. We also discuss the alternative configurations of such a strategy and,
using the best available evidence, prioritise one strategy based on delivery in
primary-level institutions (health centres), backed up by access to referral
level facilities. We then go on to discuss strategies that complement intrapartum
care. We conclude by discussing the inexplicable hesitation in decision-making
after nearly 20 years of safe motherhood programming: if the fifth Millennium
Development Goal is to be achieved, then what needs to be prioritised is obvious.
Further delays in getting on with what works begs questions about the commitment
of decision-makers to this goal.
PMID- 17027736
TI - Benign intraspinal tumour misdiagnosed as mechanical low back pain.
PMID- 17027737
TI - Belief-desire reasoning in the explanation of behavior: do actions speak louder
than words?
AB - The mechanisms underwriting our commonsense psychology, or 'theory of mind', have
been extensively investigated via reasoning tasks that require participants to
predict the action of agents based on information about beliefs and desires.
However, relatively few studies have investigated the processes contributing to a
central component of 'theory of mind' - our ability to explain the action of
agents in terms of underlying beliefs and desires. In two studies, we demonstrate
a novel phenomenon in adult belief-desire reasoning, capturing the folk notion
that 'actions speak louder than words'. When story characters were described as
searching in the wrong place for a target object, adult subjects often endorsed
mental state explanations referencing a distracter object, but only when that
object was approached. We discuss how this phenomenon, alongside other reasoning
"errors" (e.g., hindsight bias; the curse of knowledge) can be used to illuminate
the architecture of domain specific belief-desire reasoning processes.
PMID- 17027738
TI - The role of the SCRAMBLED receptor-like kinase in patterning the Arabidopsis root
epidermis.
AB - Cell-type patterning in the Arabidopsis root epidermis is achieved by a network
of transcription factors and influenced by a position-dependent mechanism. The
SCRAMBLED receptor-like kinase is required for the normal pattern to arise, but
its precise role is not understood. Here we describe genetic and molecular
studies to define the spatial and temporal role of SCM in epidermal patterning
and its relationship to the transcriptional network. Our results suggest that SCM
helps unspecified epidermal cells interpret their position in relation to the
underlying cortical cells and establish distinct cell identities. Furthermore,
SCM loss-of-function and overexpression analyses suggest that SCM influences cell
fate through its negative transcriptional regulation of the WEREWOLF MYB gene in
epidermal cells at the H position. We also find that SCM function is specifically
required for patterning the post-embryonic root epidermis and not for the
analogous epidermal cell-type patterning during embryogenesis or hypocotyl
development. In addition, we show that two closely related SCM-like genes in
Arabidopsis (SRF1 and SRF3) are not required alone or together with SCM for
proper epidermal patterning. These findings help define the developmental and
mechanistic role of SCM and suggest a new model for its action in root epidermal
cell patterning.
PMID- 17027739
TI - The immune gene repertoire encoded in the purple sea urchin genome.
AB - Echinoderms occupy a critical and largely unexplored phylogenetic vantage point
from which to infer both the early evolution of bilaterian immunity and the
underpinnings of the vertebrate adaptive immune system. Here we present an
initial survey of the purple sea urchin genome for genes associated with
immunity. An elaborate repertoire of potential immune receptors, regulators and
effectors is present, including unprecedented expansions of innate pathogen
recognition genes. These include a diverse array of 222 Toll-like receptor (TLR)
genes and a coordinate expansion of directly associated signaling adaptors.
Notably, a subset of sea urchin TLR genes encodes receptors with structural
characteristics previously identified only in protostomes. A similarly expanded
set of 203 NOD/NALP-like cytoplasmic recognition proteins is present. These genes
have previously been identified only in vertebrates where they are represented in
much lower numbers. Genes that mediate the alternative and lectin complement
pathways are described, while gene homologues of the terminal pathway are not
present. We have also identified several homologues of genes that function in
jawed vertebrate adaptive immunity. The most striking of these is a gene cluster
with similarity to the jawed vertebrate Recombination Activating Genes 1 and 2
(RAG1/2). Sea urchins are long-lived, complex organisms and these findings reveal
an innate immune system of unprecedented complexity. Whether the presumably
intense selective processes that molded these gene families also gave rise to
novel immune mechanisms akin to adaptive systems remains to be seen. The genome
sequence provides immediate opportunities to apply the advantages of the sea
urchin model toward problems in developmental and evolutionary immunobiology.
PMID- 17027740
TI - The sea urchin kinome: a first look.
AB - This paper reports a preliminary in silico analysis of the sea urchin kinome. The
predicted protein kinases in the sea urchin genome were identified, annotated and
classified, according to both function and kinase domain taxonomy. The results
show that the sea urchin kinome, consisting of 353 protein kinases, is closer to
the Drosophila kinome (239) than the human kinome (518) with respect to total
kinase number. However, the diversity of sea urchin kinases is surprisingly
similar to humans, since the urchin kinome is missing only 4 of 186 human
subfamilies, while Drosophila lacks 24. Thus, the sea urchin kinome combines the
simplicity of a non-duplicated genome with the diversity of function and
signaling previously considered to be vertebrate-specific. More than half of the
sea urchin kinases are involved with signal transduction, and approximately 88%
of the signaling kinases are expressed in the developing embryo. These results
support the strength of this nonchordate deuterostome as a pivotal developmental
and evolutionary model organism.
PMID- 17027741
TI - Trophoblast adhesion of the peri-implantation mouse blastocyst is regulated by
integrin signaling that targets phospholipase C.
AB - Integrin signaling modulates trophoblast adhesion to extracellular matrices
during blastocyst implantation. Fibronectin (FN)-binding activity on the apical
surface of trophoblast cells is strengthened after elevation of intracellular
Ca(2+) downstream of integrin ligation by FN. We report here that
phosphoinositide-specific phospholipase C (PLC) mediates Ca(2+) signaling in
response to FN. Pharmacological agents used to antagonize PLC (U73122) or the
inositol phosphate receptor (Xestospongin C) inhibited FN-induced elevation of
intracellular Ca(2+) and prevented the upregulation of FN-binding activity. In
contrast, inhibitors of Ca(2+) influx through either voltage-gated or non-voltage
gated Ca(2+) channels were without effect. Inhibition of protein tyrosine kinase
activity by genistein, but not G-protein inhibition by suramin, blocked FN
induced intracellular Ca(2+) signaling and upregulation of adhesion, consistent
with involvement of PLC-gamma. Confocal immunofluorescence imaging of peri
implantation blastocysts demonstrated that PLC-gamma2, but not PLC-gamma1 nor PLC
beta1, accumulated near the outer surface of the embryo. Phosphotyrosine site
directed antibodies revealed phosphorylation of PLC-gamma2, but not PLC-gamma1,
upon integrin ligation by FN. These data suggest that integrin-mediated
activation of PLC-gamma to initiate phosphoinositide signaling and intracellular
Ca(2+) mobilization is required for blastocyst adhesion to FN. Signaling cascades
regulating PLC-gamma could, therefore, control a critical feature of trophoblast
differentiation during peri-implantation development.
PMID- 17027742
TI - Ginsenoside Re of Panax ginseng possesses significant antioxidant and
antihyperlipidemic efficacies in streptozotocin-induced diabetic rats.
AB - Diabetes mellitus is characterized by hyperglycemia and complications affecting
the eye, kidney, nerve and blood vessel. We have previously demonstrated the
occurrence of oxidative stress of streptozotocin-induced diabetic rats, preceded
by a depletion in the tissue level of glutathione. In this study, when diabetic
rats were treated with ginsenoside Re of Panax ginseng C.A. Meyer, there was a
significant reduction in blood glucose, total cholesterol and triglyceride
levels. On the other hand, oxidative stress has been implicated in the
pathogenesis of diabetes and its complications. It was found that treatment by
ginsenoside Re restored the levels of both glutathione and malondialdehyde in the
eye and kidney to those found in the control rats. This is the first report
demonstrating ginsenoside Re has significant antioxidant efficacy in diabetes,
and prevents the onset of oxidative stress in some vascular tissues. Our results
demonstrated that ginsenoside Re could lower blood glucose and lipid levels, and
exerts protective actions against the occurrence of oxidative stress in the eye
and kidney of diabetic rats. Our data also provide evidence that ginsenoside Re
could be used as an effective antidiabetic agent particularly in the prevention
of diabetic microvasculopathy.
PMID- 17027743
TI - Fluorescence- and luminescence-based methods for the determination of affinity
and activity of neuropeptide Y2 receptor ligands.
AB - With respect to the discovery and characterization of neuropeptide Y(2) receptor
ligands as pharmacological tools or potential drugs, fluorescence- and
luminescence-based assays were developed to determine both the affinity and the
activity of receptor agonists and antagonists. A flow cytometric binding assay is
described for the hY(2) receptor stably expressed in CHO cells using cy5-labeled
porcine neuropeptide Y and compared with a radioligand binding assay. Binding of
the fluorescent ligand was visualized by confocal microscopy. Stable co
transfection with the chimeric G protein Gq(i5) enabled the establishment of a
spectrofluorimetric fura-2 and a flow cytometric fluo-4 calcium assay. Further
stable expression of apoaequorin targeted to the mitochondria allowed the
establishment of an aequorin assay which could be performed in the 96-well
format. The shape of the concentration-response curves of porcine neuropeptide Y
in the presence of the Y(2)-selective receptor antagonist BIIE0246,
characteristic of either competitive or insurmountable antagonism, depended on
the period of incubation with the cells. Functional data of Y(2) receptor
agonists and antagonists determined in the fluorescence- and luminescence-based
assays were in good agreement.
PMID- 17027744
TI - Synergistic antinociceptive effects of anandamide, an endocannabinoid, and
nonsteroidal anti-inflammatory drugs in peripheral tissue: a role for endogenous
fatty-acid ethanolamides?
AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit fatty-acid amide hydrolase
(FAAH), the enzyme responsible for the metabolism of anandamide, an
endocannabinoid. It has been suggested that the mechanisms of action of NSAIDs
could be due to inhibition of cyclooxygenase (COX) and also to an increase in
endocannabinoid concentrations. In a previous study we have demonstrated that the
local analgesic interaction between anandamide and ibuprofen (a non-specific COX
inhibitor) was synergistic for the acute and inflammatory phases of the formalin
test. To test this hypothesis further, we repeated similar experiments with
rofecoxib (a selective COX-2 inhibitor) and also measured the local
concentrations of anandamide, and of two fatty-acid amides, oleoylethanolamide
and palmitoylethanolamide. We established the ED(50) for anandamide (34.52 pmol+/
17.26) and rofecoxib (381.72 pmol+/-190.86) and showed that the analgesic effect
of the combination was synergistic. We also found that paw tissue levels of
anandamide, oleoylethanolamide and palmitoylethanolamide were significantly
higher when anandamide was combined with NSAIDs and that this effect was greater
with rofecoxib. In conclusion, local injection of anandamide or rofecoxib was
antinociceptive in a test of acute and inflammatory pain and the combination of
anandamide with rofecoxib was synergistic. Finally, locally injected anandamide
with either NSAID (ibuprofen or rofecoxib) generates higher amount of fatty-acid
ethanolamides. The exact comprehension of the mechanisms involved needs further
investigation.
PMID- 17027745
TI - Montmorillonite ameliorates hyperthyroidism of rats and mice attributed to its
adsorptive effect.
AB - The present study aims to evaluate the adsorbing effect of montmorillonite on
thyroid hormone in the entero-hepatic circulation. The concentration of thyroid
hormone in the serum of hyperthyroidism model rats and in solution was measured
by radioimmunoassay and ultraviolet spectrometry, respectively. The body weight,
temperature, and consumption of food and water were observed in hyperthyroidism
model rats. Furthermore, hypoxia tolerance, sodium-pentobarbital-induced sleep
time, spontaneous activities were measured on hyperthyroidism model mice after
being treated with montmorillonite. Results showed that montmorillonite adsorbed
thyroxin (T(4)) and triiodothyronine (T(3)) in vitro. Montmorillonite at dosage
of 1.0 g/kg and 0.3 g/kg decreased thyroid hormone levels on hyperthyroidism
model rats; Montmorillonite (2.0 g/kg and 0.6 g/kg) prolonged the sleep time,
improved the hypoxia tolerant capacity and reduced the spontaneous activities of
the hyperthyroidism model mice. These results suggest montmorillonite has anti
hyperthyroidism effect attributed to its adsorptive effect.
PMID- 17027746
TI - Cardio-protective role of terazosin is possibly mediated through alteration in
thyroid function.
AB - An investigation was made to reveal the possible involvement of thyroid hormones,
if any, in terazosin (an alfa-1 adrenergic receptor blocker) induced alterations
in tissue lipid peroxidation (LPO) and in the concentration of different serum
lipids. We determined the impact of terazosin on the changes in
hypercholesterolemic (CCT) diet induced thyroid dysfunction; cardiac, renal and
hepatic LPO and on serum glucose concentration in female Wister rats.
Simultaneously levels of total cholesterol (TC), high-density lipoprotein
cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides
(TG), creatinine, alkaline phosphatase (ALP) activity, hepatic glycogen synthesis
and total daily food consumption were studied as supporting parameters. While a
decrease in the level of serum thyroid hormones, HDL-C and in hepatic glycogen
content, was observed in CCT diet fed animals; it increased the concentration of
other serum lipids, glucose and creatinine; ALP activity; tissue and serum LPO.
However, following terazosin administration for 15 days to CCT diet fed animals,
status of thyroid hormones and all other thyroid dependent parameters were
reversed suggesting that the drug might be acting through an alteration in the
thyroid functions.
PMID- 17027747
TI - Selective antagonism activity of alkaloids from bulbs Fritillariae at muscarinic
receptors: functional studies.
AB - 15 alkaloids were isolated from five Fritillariae species and 6 derivatives were
synthesized. Alkaloids having anticholinergic effect on guinea-pig tracheal
smooth muscle were screened out and their mechanism was further studied on the
cAMP formation in Chinese hamster ovary cells stably expressing human muscarinic
M2 receptor (CHO-hM2 cells) and intracellular calcium ([Ca(2+)](i)) transient in
Chinese hamster ovary cells stably expressing human muscarinic M3 receptor (CHO
hM3 cells). In normal Krebs-Henseleit (KH) solution, imperialine (15), 3beta
acetylimperialine (16) and sinpeinine A (17) concentration-dependently relaxed 1
microM carbachol-induced contraction of guinea-pig tracheal rings with EC(50) of
4.19, 1.71 and 4.67 microM, respectively. In Ca(2+)-free KH solution, 10 microM
3beta-acetylimperialine (16), imperialine (15) and sinpeinnine A (17) caused
97.42%, 5.45% and 6.55% inhibition, respectively, which indicated that the three
components might inhibit muscarinic receptor in different mechanism. Results of
muscarinic M2 receptor-inhibited cAMP formation in CHO-hM2 cells showed that
imperialine (15) and sinpeinine A (17) could potently elevate the cAMP formation
whereas 3beta-acetylimperialine (16) only had weak effect on antagonism of cAMP
inhibition. Furthermore, the investigations of muscarinic M3 receptor-stimulated
[Ca(2+)](i) transient in CHO-hM3 cells revealed that imperialine (15) and
sinpeinine A (17) could not antagonize [Ca(2+)](i) transient, but 3beta
acetylimperialine (16) significantly inhibited [Ca(2+)](i) peak elevation with an
IC(50) of 5.26 microM. The functional studies suggest that the mechanism of
relaxant action of imperialine (15) and sinpeinine A (17) is due to their
selective inhibitory effects on muscarinic M2 receptors and the mechanism of
3beta-acetylimperialine (16) originates from its selective muscarinic M3
receptors antagonism.
PMID- 17027748
TI - 4-O-methylgallic acid down-regulates endothelial adhesion molecule expression by
inhibiting NF-kappaB-DNA-binding activity.
AB - We here investigated the functional effect of 4-O-methylgallic acid (4-OMGA), a
major metabolite of gallic acid abundant in red wine, on vascular inflammation
and its action mechanism. 4-OMGA inhibited the expression of intercellular
adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in
human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis
factor-alpha (TNF-alpha), resulting in the suppression of leukocyte adhesion to
HUVECs. In addition, 4-OMGA inhibited the promoter activities of ICAM-1 and VCAM
1 and the activity of nuclear factor-kappaB (NF-kappaB) without affecting
cytosolic IkappaB kinase (IKK) activation, inhibitor of kappaB (IkappaB)
phosphorylation and degradation, and nuclear translocation of NF-kappaB. This
compound did not alter nitric oxide (NO) generation, but inhibited reactive
oxygen species (ROS) production in TNF-alpha-stimulated HUVECs, suggesting that
NO and ROS are not involved in 4-OMGA-mediated inhibition of NF-kappaB activity.
Moreover, 4-OMGA directly blocked the binding activity of NF-kappaB to its
consensus DNA oligonucleotide, when pre-incubated with the nuclear extract from
TNF-alpha-stimulated HUVECs, but not with the oligonucleotide alone. This
inhibition was completely abolished by the addition of dithiothreitol. 4-OMGA
exhibits an anti-inflammatory property by interfering with the formation of the
NF-kappaB-DNA complex in the nuclei through direct and redox-sensitive
interactions and may play an important role in the prevention of inflammatory
responses such as the atherosclerotic process.
PMID- 17027749
TI - Adenosine A1 receptor antagonist versus montelukast on airway reactivity and
inflammation.
AB - Adenosine produces bronchoconstriction in allergic rabbits, primates, and humans
by activating adenosine A(1) receptors. Previously, it is reported that a high
dose of L-97-1, a water-soluble, small molecule adenosine A(1) receptor
antagonist, blocks early and late allergic responses, and bronchial hyper
responsiveness to histamine in a hyper-responsive rabbit model of allergic
asthma. Effects of a lower dose of L-97-1 are compared to montelukast, a
cysteinyl leukotriene-1 receptor antagonist on early allergic response, late
allergic response, bronchial hyper-responsiveness, and inflammatory cells in
bronchoalveolar lavage (BAL) fluid following house dust mite administration.
Rabbits received intraperitoneal injections of house dust mite extract within 24
h of birth followed by booster house dust mite injections. Hyper-responsive
rabbits received aerosolized house dust mite (2500 allergen units), 1 h after
intragastric administration of L-97-1 (1 mg/kg) or montelukast (0.15 mg/kg) and
lung dynamic compliance was measured for 6 h. Lung dynamic compliance was
significantly higher following L-97-1 at all time points and with montelukast at
60-300 min following house dust mite (P<0.05). L-97-1 blocks both early and late
allergic responses. Montelukast blocks only the late allergic response. Both L-97
1 and montelukast significantly blocked bronchial hyper-responsiveness at 24 h
(P<0.05). Both L-97-1 and montelukast significantly reduced BAL eosinophils at 6
h and neutrophils at 6 and 24 h (P<0.05). L-97-1 significantly reduced BAL
lymphocytes at 6 and 24 h (P<0.05). Montelukast significantly reduced BAL
macrophages at 6 and 24 h (P<0.05). By blocking both bronchoconstriction and
airway inflammation, L-97-1 may be an effective oral anti-asthma treatment.
PMID- 17027750
TI - Antidepressants enhance the antinociceptive effects of carbamazepine in the
acetic acid-induced writhing test in mice.
AB - Some antidepressants, as well as antiepileptics, are effective for treating pain
of varying etiology. The present study was designed to characterize the
antinociceptive effects of imipramine, a tricyclic antidepressant, fluvoxamine, a
selective serotonin reuptake inhibitor, milnacipran, a serotonin noradrenaline
reuptake inhibitor, and carbamazepine, an antiepileptic drug, using the acetic
acid-induced writhing test in mice. Imipramine (1.25-10 mg/kg, i.p.), fluvoxamine
(5-40 mg/kg, i.p.) and milnacipran (2.5-20 mg/kg, i.p.) all dose-dependently and
significantly reduced the number of writhes induced by the injection of acetic
acid (0.8% (v/v)), although the maximal effect of milnacipran was weaker than
those of imipramine and fluvoxamine. Similarly, carbamazepine (5-20 mg/kg, i.p.)
also showed a dose-dependent and significant antinociceptive effect. In
combination studies, the co-administration of a sub-effective dose of
carbamazepine (5 mg/kg, i.p.) with imipramine (1.25 and 2.5 mg/kg, i.p.),
fluvoxamine (10 mg/kg, i.p.) or milnacipran (1.25 and 2.5 mg/kg, i.p.)
significantly reduced the number of writhes. Additionally, the hole-board test
revealed that the medications with significant antinociceptive effects barely
produced changes in motor activity that could possibly affect writhing behavior.
Thus, the present study demonstrated that the antinociceptive effect of
carbamazepine is enhanced by combination with imipramine, fluvoxamine and
milnacipran. Therefore, the combined therapy using antidepressants and
carbamazepine may be useful clinically for the control of pain.
PMID- 17027751
TI - Nicotine administration enhances conditioned inhibition in rats.
AB - The effect of nicotine on conditioned inhibition was examined using a serial
feature negative discrimination task. Nicotine (0.35 mg/kg) or vehicle was
administered before each of the 16 training sessions. On some trials in each
session, a tone was presented and followed by food reward. On other trials, the
tone was preceded by a visual stimulus and not reinforced. Nicotine-treated rats
exhibited greater discrimination between the two trial types as evidenced by less
frequent responding during non-reinforced trials, and learned the discrimination
in fewer sessions than vehicle-treated rats. In contrast, there were no group
differences in responding during the reinforced trials.
PMID- 17027752
TI - ZNF198, a zinc finger protein rearranged in myeloproliferative disease, localizes
to the PML nuclear bodies and interacts with SUMO-1 and PML.
AB - The ZNF198/FGFR1 fusion gene in atypical myeloproliferative disease produces a
constitutively active cytoplasmic tyrosine kinase, unlike ZNF198 which is
normally a nuclear protein. We have now shown that the ZNF198/FGFR1 fusion kinase
interacts with the endogenous ZNF198 protein suggesting that the function of
ZNF198 may be compromised in cells expressing it. Little is currently known about
the endogenous function of ZNF198 and to investigate this further we performed a
yeast two-hybrid analysis and identified SUMO-1 as a binding partner of ZNF198.
These observations were confirmed using co-immunoprecipitation which demonstrated
that ZNF198 is covalently modified by SUMO-1. Since many of the SUMO-1-modified
proteins are targeted to the PML nuclear bodies we used confocal microscopy to
show that SUMO-1, PML and ZNF198 colocalize to punctate structures, shown by
immunocytochemistry to be PML bodies. Using co-immunoprecipitation we now show
that PML and sumoylated ZNF198 can be found in a protein complex in the cell.
Mutation of the SUMO-1 binding site in wild-type ZNF198 resulted in loss of
distinct PML bodies, reduced PML levels and a more dispersed nuclear localization
of the PML protein. In cells expressing ZNF198/FGFR1, which also lack the SUMO-1
binding site, SUMO-1 is preferentially localized in the cytoplasm, which is
associated with loss of distinct PML bodies. Recently, arsenic trioxide (ATO) was
proposed as an alternative therapy for APL that was resistant to traditional
therapy. Treatment of cells expressing ZNF198/FGFR1 with ATO demonstrated reduced
autophosphorylation of the ZNF198/FGFR1 protein and induced apoptosis, which is
not seen in cells expressing wild-type ZNF198. Overall our results suggest that
the sumoylation of ZNF198 is important for PML body formation and that the
abrogation of sumoylation of ZNF198 in ZNF198/FGFR1 expressing cells may be an
important mechanism in cellular transformation.
PMID- 17027754
TI - Effects of latanoprost on rodent intraocular pressure.
AB - The aim of the present study was to evaluate the effects of the prostaglandin F2
alpha analog, latanoprost, on the intraocular pressure (IOP) in rodent eyes.
Rodents have been increasingly used in glaucoma research; however, conflicting
results regarding the actions of prostaglandins on rodent IOP have been
published. In Wistar rats, a single dose of latanoprost (60 ng) produced a
biphasic change in IOP: an initial rise in pressure (2.1+/-0.7 mmHg) peaking at 2
h, followed by a prolonged hypotension with a peak reduction in IOP (5.2+/-0.7
mmHg) at 5 h. Both the hyper and hypotensive actions of latanoprost were dose
related with ED50 values of 108 and 5.2 ng, respectively. These responses were
antagonized by pretreatment with 4% pilocarpine. In Brown Norway rats and C57BL/6
mice, a single dose of latanoprost also produced a biphasic response in IOP with
an initial rise in pressure peaking between 1 and 2 h, followed by prolonged
hypotension from 4 to 8 h. These results demonstrate that in rodents the IOP
response to topical latanoprost is characterized by an initial hypertension
followed by a prolonged hypotension. This prolonged hypotension is similar to
that measured in monkeys and humans. Taken together, these results support the
idea that rodents can serve as in vivo models to study the actions of ocular
hypotensive agents, such as prostaglandins.
PMID- 17027753
TI - Epithelial-mesenchymal transition occurs after epidermal development in mouse
skin.
AB - In the present study, we studied epithelial-mesenchymal transition (EMT) with
fetal and postnatal serial skin sections. E-cadherin, occludin and zonula
occludens 1 (ZO-1)-expressing cells appear in the dermal area from E18.5 to
postnatal day 9 (P9), with highest expression from P2 to P5. The co-expression of
mesenchymal marker alpha-smooth muscle (alpha-SMA), fibronectin and vimentin with
E-cadherin in these dermal cells was further examined. Almost no dermal cells
express alpha-SMA before P0. From P2 to P6, cells expressing both E-cadherin and
alpha-SMA appear in the dermis. In contrast, fibronectin-releasing cells were
detected in the dermis as early as on E15.5, although on P5, some dermal cells
was found weakly expressing both fibronectin and E-cadherin, most cells strongly
expressing fibronectin did not express E-cadherin. Vimentin was mainly expressed
in both endothelial and blood-derived cells and did not show co-expression with E
cadherin. Confocal microscopy studies further found that during EMT, E-cadherin
appears intracellularly, while the expression of alpha-SMA starts from the
membrane area and moves to the cytosol of the cells. Our data are the first in
vivo evidence that EMT occurs during mouse skin development. Dermal cells are
derived from EMT and other origins, including blood, during skin development.
PMID- 17027755
TI - Differential effects of water deprivation and rehydration on Fos and
FosB/DeltaFosB staining in the rat brainstem.
AB - This study examined the effects of dehydration and rehydration with water on Fos
and FosB staining in the brainstem of rats. Male rats were water deprived for 48
h (Dehyd, n=7) or 46 h followed by 2 h access to water (Rehyd, n=7). Controls had
ad libitum access to water (Con, n=9). Brainstems were stained for Fos and
FosB/DeltaFosB using commercially available antibodies. In the nucleus of the
solitary tract (NTS), the number of Fos stained neurons was significantly
increased by dehydration and increased further following rehydration (Con 5+/-1;
Dehyd 22+/-1; Rehyd 48+/-5). The average number of Fos-positive cells in the
parabrachial nucleus (PBN) was significantly increased only by rehydration (Con
12+/-2; Dehyd 6+/-2; Rehyd 51+/-4). The area postrema (AP) showed significant
increases in Fos staining after dehydration and rehydration (Fos: Con 4+/-1;
Dehyd 28+/-3; Rehyd 24+/-3). In the rostral ventrolateral medulla (RVL), Fos
staining significantly increased after dehydration and this effect was reduced by
rehydration (Con 3+/-1; Dehyd 21+/-2; Rehyd 12+/-1). In contrast, Fos staining in
the caudal ventrolateral medulla (CVL) was not significantly influenced following
either dehydration or rehydration with water (Con 4+/-1; Dehyd 4+/-1; Rehyd 5+/
1). FosB/DeltaFosB staining in the NTS, AP, and RVL was comparably increased by
dehydration and rehydration. In the PBN and CVL, FosB/DeltaFosB staining was not
affected by the treatments. Dehydration and rehydration have regionally specific
effects on Fos and FosB/DeltaFosB staining in the brainstem.
PMID- 17027756
TI - Transcriptional activation of the proapoptotic bik gene by E2F proteins in cancer
cells.
AB - BH3-only proteins are required for execution of apoptotic cell death. We have
found that one of these proteins, Bik, is strongly induced in cancer cells
treated with chemotherapeutic agents. Furthermore, we showed that chemotherapy
induced expression of bik is independent of p53. Consistent with its pro
apoptotic activity, blockade of bik expression reduces the adriamycin-mediated
apoptotic cell death. We also found that the bik gene is transcriptionally
activated by E2F proteins. Consistently, adriamycin induces the E2F-bik pathway.
In addition, E2Fs transactivate bik by a p53-independent mechanism. Thus, our
data indicate that transcriptional regulation of bik contributes to the efficient
apoptotic response to chemotherapeutic agents.
PMID- 17027757
TI - Regulation of Stat3 transcriptional activity by the conserved LPMSP motif for OSM
and IL-6 signaling.
AB - To achieve maximal transcriptional activity in response to gp130 cytokines,
Serine-727 (Ser-727) of Stat3 is phosphorylated. Ser-727 resides in the LPMSP
motif, the only conserved sequence among the transcription activation domains of
several STATs. We show here that in addition to Ser-727, other residues in this
LPMSP motif are also required for Stat3 activity in response to cytokine
signaling through regulation of Ser-727 phosphorylation and recruitment of the
transcription co-activator CBP/p300 to the promoters of Stat3-target genes for
transcription activation. Hence, we have demonstrated a critical role for the
whole conserved LPMSP motif in JAK-STAT signaling.
PMID- 17027758
TI - Respective importance of protein folding and glycosylation in the thermal
stability of recombinant feruloyl esterase A.
AB - The thermal stability of four molecular forms (native, refolded, glycosylated,
non-glycosylated) of feruloyl esterase A (FAEA) was studied. From the most to the
least thermo-resistant, the four molecular species ranked as follows: (i)
glycosylated form produced native, (ii) non-glycosylated form produced native,
(iii) non-glycosylated form produced as inclusion bodies and refolded, and (iv)
glycosylated form produced native chemically denatured and then refolded. On the
basis of these results and of crystal structure data, we discuss the respective
importance of protein folding and glycosylation in the thermal stability of
recombinant FAEA.
PMID- 17027759
TI - Counting abortions so that abortion counts: Indicators for monitoring the
availability and use of abortion care services.
AB - SUMMARY: Maternal mortality reduction has been a focus of major international
initiatives for the past two decades. Widespread provision of emergency obstetric
care (EmOC) has been shown to be an important strategy for addressing many of the
complications that might otherwise lead to maternal death. However, unsafe
abortion is one of the major causes of pregnancy-related deaths, and will be only
partially addressed by EmOC. This manuscript presents a comprehensive approach to
measuring whether abortion-related needs are met. PROPOSED METHODS: We propose a
set of indicators for monitoring the implementation of safe abortion care (SAC)
interventions. We build on the model developed for monitoring the availability
and use of Emergency Obstetric (EmOC) services. We describe the critical elements
("signal functions") of SAC - including treatment of abortion complications,
legal, induced abortion and postabortion contraception - and define the
indicators necessary to assess the availability, utilization and quality of
abortion-related services. SAMPLE EVIDENCE: Data from 5 countries suggest there
are sufficient service delivery points to provide decentralized abortion care,
but that the full range of necessary abortion care services may not be provided
at all these sites. Studies from several countries also show that many women
receiving services for the treatment of abortion complications accept
contraceptive methods when offered prior to discharge. This is an important
strategy for reducing unwanted pregnancy, repeat unsafe abortion and risk for
abortion-related mortality. Both findings suggest there are considerable
opportunities within the present facilities to improve the delivery of abortion
care services. CONCLUSION: This article recommends that the proposed model
undergo field-testing on its own or in conjunction with the EmOC indicators, and
encourages increased support for this important but often neglected aspect of
pregnancy-related health.
PMID- 17027760
TI - Characterization of a Trypanosoma cruzi antigen with homology to intracellular
mammalian lectins.
AB - Two cDNAs, isolated from a Trypanosoma cruzi amastigote library immunoscreened
with sera from patients with Chagas disease, encode proteins with sequence
homology to eukaryotic components of the cellular sorting and recycling
machinery. These proteins, denominated TcAGL, present an N-terminal lectin domain
and a C-terminal region containing repetitive amino acids and a poly-glutamine
tract. They are products of polymorphic alleles of a single copy gene
constitutively expressed during the parasite life cycle. Polyclonal antibodies
obtained from mice immunized with the recombinant antigen recognize proteins with
apparent molecular weight ranging from 95 to 120 kDa in cell lysates from all
three life stages and in various strains of the parasite. Sera from Chagas
disease patients recognize the recombinant antigen in ELISA and
immunoprecipitation assays but not in Western blot assays under denaturing
conditions. Consistent with its proposed role in the glycoprotein secreting
pathway, immunofluorescence analyses and expression of a green fluorescent
protein-tagged TcAGL protein indicate a sub-cellular localization in the vicinity
of the flagellar pocket membrane and the Golgi complex of the parasite.
PMID- 17027761
TI - Independent component model of the default-mode brain function: Assessing the
impact of active thinking.
AB - The "default-mode" network is an ensemble of cortical regions, which are
typically deactivated during demanding cognitive tasks in functional magnetic
resonance imaging (fMRI) studies. Using functional connectivity, this network can
be conceptualized and studied as a "stand-alone" function or system. Regardless
of the task, independent component analysis (ICA) produces a picture of the
"default-mode" function even when the subject is performing a simple sensori
motor task or just resting in the scanner. This has boosted the use of default
mode fMRI for non-invasive research in brain disorders. Here, we studied the
effect of cognitive load modulation of fMRI responses on the ICA-based pictures
of the default-mode function. In a standard graded working memory study based on
the n-back task, we used group-level ICA to explore the variability of the
default-mode network related to the engagement in the task, in 10 healthy
volunteers. The analysis of the default-mode components highlighted similarities
and differences in the layout under three different cognitive loads. We found a
load-related general increase of deactivation in the cortical network.
Nonetheless, a variable recruitment of the cingulate regions was evident, with
greater extension of the anterior and lesser extension of the posterior clusters
when switching from lower to higher working memory loads. A co-activation of the
hippocampus was only found under no working memory load. As a generalization of
our results, the variability of the default-mode pattern may link the default
mode system as a whole to cognition and may more directly support use of the ICA
model for evaluating cognitive decline in brain disorders.
PMID- 17027762
TI - Light-induced Fos expression in the suprachiasmatic nucleus of the four-striped
field mouse, Rhabdomys pumilio: A southern African diurnal rodent.
AB - Previous studies have suggested that nocturnal and diurnal species of rodents
differ in their circadian responses to light including phase shifts and early
gene expression. Rhabdomys pumilio, the four-striped field mouse, is diurnal both
in nature and in the laboratory. We studied in this species the response of the
suprachiasmatic nucleus (SCN) to light stimuli at different time periods using
light-induced expression of Fos as marker of neuronal activity. Fos induction in
the SCN was investigated using immunohistochemistry and quantitative image
analysis. The animals were exposed to a 15 min light pulse with monochromatic
green light at different circadian times throughout a 24-h cycle. Animals
maintained in constant darkness served as controls. R. pumilio exhibited an
endogenous Fos rhythm in the SCN during constant darkness with highest expression
during the subjective day at circadian time (CT) 2 and CT10. Photic stimulation
resulted in significant Fos induction in the SCN at CT6, CT14, CT18 and CT22,
compared to controls kept in constant darkness, with a peak of expression at
CT22, i.e. during late subjective night, mainly due to expression in the ventral
SCN. In tract tracing experiments based on the use of cholera toxin subunit B, we
found that retinal fibres innervate mainly the contralateral ventral SCN. The
intergeniculate leaflet received bilateral retinal innervation with overlap
between ipsilateral and contralateral fibres. Altogether the data show that the
rodent R. pumilio is a unique diurnal model for chronobiological studies.
PMID- 17027763
TI - Glutamatergic innervation of growth hormone-releasing hormone-containing neurons
in the hypothalamic arcuate nucleus and somatostatin-containing neurons in the
anterior periventricular nucleus of the rat.
AB - Growth hormone-releasing hormone (GHRH) and somatostatin are the two main
hypothalamic neurohormones, which stimulate or inhibit directly hypophysial
growth hormone (GH) release. Majority of the GHRH neurons projecting to the
median eminence is situated in the arcuate nucleus and the somatostatin neurons
in the anterior periventricular nucleus. Data suggest that the excitatory amino
acid glutamate may play an important role in the control of hypothalamic
neuroendocrine neurons and processes including the control of GH. There is a
dense plexus of glutamatergic fibres in the hypothalamic arcuate and anterior
periventricular nucleus. The aim of the present studies was to examine the
relationship of these fibres to the GHRH neurons in the arcuate nucleus and to
somatostatin neurons in the anterior periventricular nucleus. Double-labelling
immuno-electron microscopy was used. Glutamatergic structures were identified by
the presence of vesicular glutamate transporter 2 (VGluT2) (a selective marker of
glutamatergic elements) immunoreactivity. A significant number of VGluT2
immunoreactive boutons was observed to make asymmetric type of synapses with GHRH
immunostained nerve cells in the arcuate and with somatostatin neurons in the
anterior periventricular nucleus. A subpopulation of somatostatin-immunoreactive
neurons displayed also VGluT2 immunoreactivity. Our findings provide direct
neuromorphological evidence for the view that the action of glutamate on GH
release is exerted, at least partly, directly on GHRH and somatostatin neurons
releasing these neurohormones into the hypophysial portal blood.
PMID- 17027764
TI - Temporal dynamics of face repetition suppression.
AB - Single-unit recordings and functional brain imaging studies have shown reduced
neural responses to repeated stimuli in the visual cortex. Using MEG, we compared
responses evoked by repetitions of neutral faces to those evoked by fearful
faces, which were either task relevant (targets) or irrelevant (distracters).
Faces evoked a bi-phasic response in extrastriate cortex, peaking at 160-185 ms
and at 220-250 ms, with stronger responses to neutral faces at the earlier
interval and stronger responses to fearful faces at the later interval. At both
latencies, repetitions of neutral and fearful targets resulted in reduced
amplitude of the MEG signal. Additionally, we found that the context in which
targets were presented affected their processing: fearful distracters increased
the responses evoked by both neutral and fearful targets. Our data indicate that
valence enhancement and context effects can be detected in extrastriate visual
cortex within 250 ms and that these processes likely reflect feedback from other
regions.
PMID- 17027765
TI - Relative expression of D3 dopamine receptor and alternative splice variant D3nf
mRNA in high and low responders to novelty.
AB - Studies in rodents suggest an important role for the D3 dopamine receptor in
regulating locomotor responses to spatial novelty and psychostimulants. The D3
receptor alternatively spliced variant D3nf produces a non-dopamine binding
protein that may alter D3 receptor localization by dimerizing with the full
length receptor. In the high responder/low responder (HR/LR) model, the locomotor
response to an inescapable, novel spatial environment predicts individual
differences in the locomotor and rewarding effects of psychostimulants. We
hypothesized that individual differences in D3 receptor expression could
contribute to individual differences in the locomotor response to novelty in the
HR/LR model. To test this hypothesis, we screened rats for response to a novel
spatial environment and analyzed brain tissue for mRNA levels of the D3 receptor
and D3nf by real-time RT-PCR. The ratios of D3/D3nf mRNA in prefrontal cortex and
substantia nigra/ventral tegmentum were significantly lower in HRs than in LRs.
There were no differences in relative expression of D3/D3nf between HRs and LRs
in nucleus accumbens. These data further support a role for the D3 dopamine
receptor in behavioral responses to novelty and, given the established
relationship between novelty and psychostimulant responses, suggest that the D3
receptor may be an important target for assessment of drug abuse vulnerability.
Additionally, these findings are consistent with the hypothesis that alternative
splicing may contribute to regulation of D3 dopamine receptor function.
PMID- 17027766
TI - Blood content modulates the induction of heat shock proteins in the neurovascular
network.
AB - Heat shock proteins are ubiquitous members of a family of molecular chaperones
that protect various cell populations from injury. Up-regulation of heat shock
proteins, particularly the 70 kDa species, bind selectively to denatured or
partially damaged polypeptides that would otherwise perturb cell function and
initiate cell death programs. In this regard, induction of heat shock proteins
provides protection from cerebral ischemia in animal models of stroke.
Endothelial cells, in particular, are intimately involved in the above protective
event as these cells mount a stress response with induction of the 70 kDa heat
shock protein. However, the coupling of heat shock proteins and the neurovascular
response are not yet known. Here we show that blood content is an important
factor in this stress response as rats devoid of blood content do not display a
heat shock response in the microvasculature of the hippocampal formation. This
lack of stress response, however, is reversed when rats are reperfused with
exogenous rat or human blood content. We propose a new ischemic-sensing role for
blood that serves to integrate information about protein-damaging conditions and
heat shock protein levels in the neurovascular network. Further characterization
of this sensing role could represent an attractive new approach to treatment of
global ischemia and other microvascular pathologies.
PMID- 17027767
TI - Negative symptoms: A review of schizophrenia, melancholic depression and
Parkinson's disease.
AB - Negative symptoms generally refer to a reduction in normal functioning. In
schizophrenia they encompass apathy, anhedonia, flat affect, avolition, social
withdrawal and, on some accounts, psychomotor retardation. Negative symptoms have
been identified in other psychiatric disorders, including melancholic depression,
and also in neurological disorders, such Parkinson's disease. Achieving a better
understanding of negative symptoms constitutes a priority in mental health.
Primarily, negative symptoms represent an unrelenting, intractable and disabling
feature for patients, often amounting to a severe burden on families, carers and
the patients themselves. Identifying and understanding subgroups within disorders
may also contribute to the clinical care and scientific understanding of the
pathophysiology of these disorders. The purpose of this paper is to review the
current literature on negative symptoms in schizophrenia and explore the idea
that negative symptoms may play an important role not only in other psychiatric
disorders such as melancholic depression, but also in neurological disorders,
such as Parkinson's disease. In each disorder negative symptoms manifest with
similar motor and cognitive impairments and are associated with comparable
neuropathological and biochemical findings, possibly reflecting analogous
impairments in the functioning of frontostriatal-limbic circuits.
PMID- 17027768
TI - The prefrontal cortex in the Gottingen minipig brain defined by neural projection
criteria and cytoarchitecture.
AB - In an attempt to delineate the prefrontal cortex (PFC) in the Gottingen minipig
brain the distribution of reciprocal thalamocortical projections was investigated
using anterograde and retrograde tracing techniques and evaluated in relation to
the specific cytoarchitectonic organization. Tracers were visualized using
standard immunohistochemistry or evaluated in vivo using manganese (Mn2+) as an
MRI paramagnetic tracer. The in vivo tract tracing turned out to be very
sensitive with a high correspondence to the histological labelling. Tracers
injected into the mediodorsal thalamus labelled the medial and rostral pole of
the frontal lobe as well as the anterior cingulate, anterior insular and
dorsomedial frontal cortices. Subsequently, the reciprocity and specificity of
these connections were tested from injections into the traced frontal cortices
indicating that the PFC has cortical connections to different parts of the MD
nucleus. Although the granular layer IV, characteristic of primate PFC could not
be identified, both cytoarchitectonic and connectional data suggests that the
Gottingen minipig has a structurally divided prefrontal cortex. Stereological
estimates of PFC volume showed that the Gottingen minipig PFC constitutes about
24% of the total neocortex volume and 10% of the total brain volume.
PMID- 17027769
TI - Differential effects of age on sequence learning and sensorimotor adaptation.
AB - Although many studies have documented declines in the ability of the elderly to
learn new manual motor skills, studies have not directly compared the capacity of
older adults to learn sequences versus adapt to sensorimotor perturbations within
the context of the same task paradigm, despite differences in the underlying
neural mechanisms and strategic processes supporting the two types of learning.
The purpose of the current study was to exploit these task differences in an
effort to determine whether aging results in a generalized or more specific skill
learning deficit. Groups of young and older adult subjects learned to make a
sequence of actions, adapted to one of two visuomotor rotations, or adapted to an
altered gain of display, all while performing the same basic manual joystick
aiming task. While the older adults exhibited normal sequence learning in
comparison to the young adults, they exhibited impairments in all three of the
adaptation tasks. These deficits in adaptation for the older adults were
associated with hypometric movements and reduced velocity modulation in
comparison to that seen in the younger adults. These data suggest that older
adults may have greater difficulty with learning cerebellar-mediated motor
skills.
PMID- 17027770
TI - NMDA receptor activity in learning spatial procedural strategies I. The influence
of hippocampal lesions.
AB - To acquire knowledge about the environment two types of learning are necessary:
declarative localizatory learning about where environmental cues and the subject
are, and procedural learning about how to explore and move around the
environment. Experimental data indicate that hippocampal regions are involved in
spatial learning, playing a key role in building spatial cognitive maps. The
contribution of hippocampal NMDA receptors to spatial functions is indicated by
the disruption of place learning when NMDA long-term potentiation is blocked.
Conversely, the hippocampal contribution to the acquisition of procedural
strategies is still controversial. Inactivation of the hippocampus by
antagonizing the activity of AMPA/kainate receptors results in impaired spatial
procedural learning. However, in the presence of a blockade of NMDA long-term
potentiation in hippocampal areas it is still possible to learn explorative
strategies. To investigate the involvement of the hippocampal NMDA receptors in
spatial procedural learning, an NMDA receptor antagonist (CGS 19755) was
administered i.p. to unlesioned animals or to animals with total ablation of
hippocampal structures that had been tested in the Morris water maze. The CGS
administration induced peripheral circling in both unlesioned control animals and
in rats with bilateral hippocampal ablation. Conversely, circling was not
observed if the drug-treated animals (either unlesioned or lesioned) had been
spatially trained before drug administration. These findings indicate that even
in the absence of the hippocampal formation the NMDA receptor antagonist found a
site of action to influence the acquisition of spatial procedures to search for
the platform.
PMID- 17027771
TI - NMDA receptor activity in learning spatial procedural strategies II. The
influence of cerebellar lesions.
AB - Experimental data support the involvement of cerebellar circuits in the
acquisition of spatial procedural competences. Since the ability to acquire new
procedural competences is lost when cerebellar regions are lesioned or when NMDA
receptor activity is blocked, we analyzed whether the learning of explorative
strategies is affected by blocking NMDA receptor activity in the presence of
cerebellar lesions. To this aim, the NMDA receptor antagonist (CGS 19755, 7
mg/kg) was administered i.p. to un-lesioned rats, or rats subjected to total
ablation of the cerebellum or to hemi-cerebellectomy. CGS 19755 and
cerebellectomy both produced water maze behavior characterized by circling.
Administration of CGS 19755 did not modify the Morris Water Maze (MWM) peripheral
circling behavior of cerebellectomized animals. Circling was the dominant
strategy of hemicerebellectomized animals in the absence of drugs. However,
increasingly compulsive circling was observed under the action of CGS 19755.
Circling was not observed if the drug-treated animals (un-lesioned or lesioned)
had been previously trained. In conclusion, the NMDA antagonist caused severe
impairment in the acquisition of spatial procedures, thus mimicking the
consequences of cerebellar ablation on spatial procedural learning. Based on the
present findings, we hypothesize that cerebellar NMDA receptor activity is
involved in the acquisition of procedural spatial competence.
PMID- 17027772
TI - Acute effects of moclobemide and deprenyl on 5-HT synthesis rates in the rat
brain: An autoradiographic study.
AB - Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) released from nerve
terminals in the brain are primarily removed from the synaptic cleft by a
reuptake mechanism. In part, the homeostasis is maintained by monoamine oxidase
(MAO) deamination achieved primarily intracellularly. The present study's aim was
to examine the effect of the acute administration of the MAO inhibitors,
moclobemide (a MAO-A inhibitor) and deprenyl (a MAO-B inhibitor), on 5-HT
synthesis rates, measured in discrete regions of the rat brain by an
autoradiographic method, using alpha-[14C]methyl-l-tryptophan as a tracer. MAO
inhibitors have different effects on 5-HT synthesis rates in the cell bodies and
areas of the nerve terminals. Moclobemide (10 mg/kg, i.p. 30 min before the
tracer injection) and deprenyl (3 mg/kg, i.p. 2 h before the tracer injection)
decreased the 5-HT synthesis rates in the dorsal (-18% and -22%) and median (-22%
and -33%) raphe, respectively. Moclobemide also significantly decreased 5-HT
synthesis in the entire nerve terminal areas investigated. The reductions were
between 23% (cingulate cortex) and 50% (locus coeruleus). Deprenyl did not
significantly affect 5-HT synthesis in the nerve terminals. The present results
suggest that MAO-A, and to a lesser extent, MAO-B, are involved in the regulation
of 5-HT synthesis in the rat brain. The mechanism(s) of MAO inhibitors' action on
5-HT synthesis in the raphe nuclei are probably related to an increase in the
extraneuronal 5-HT concentration and also to the interaction between the
serotonergic and catecholaminergic neurons. The reduction of 5-HT synthesis in
the raphe nuclei likely occurs by an action of extracellular 5-HT via the
dendritic autoreceptors with a possible contribution from the action of
extracellular DA and NE. In the terminal regions, the most likely mechanism is
via the presynaptic autoreceptors through which elevated extraneuronal 5-HT acts
on synthesis control. However, there is also a possibility that the elevation in
intraneuronal 5-HT directly inhibits its synthesis, especially following deprenyl
treatment. A great influence of moclobemide on 5-HT synthesis could be related to
its antidepressant action.
PMID- 17027773
TI - Peripheral mGluR5 antagonist attenuated craniofacial muscle pain and inflammation
but not mGluR1 antagonist in lightly anesthetized rats.
AB - The present study investigated the role of peripheral group I metabotropic
glutamate receptors (mGluRs) in MO-induced nociceptive behaviour and inflammation
in the masseter muscles of lightly anesthetized rats. Experiments were carried
out on male Sprague-Dawley rats weighing 300-400 g. After initial anesthesia with
sodium pentobarbital (40 mg/kg, i.p.), one femoral vein was cannulated and
connected to an infusion pump for intravenous infusion of sodium pentobarbital.
The rate of infusion was adjusted to provide a constant level of anesthesia.
Mustard oil (MO, 30 microl) was injected into the mid-region of the left masseter
muscle via a 30-gauge needle over 10s. After 30 microl injection of 5, 10, 15, or
20% MO into the masseter muscle, the total number of hindpaw shaking behaviour
and extravasated Evans' blue dye concentration in the masseter muscle were
significantly higher in the MO-treated group in a dose-dependent manner compared
with the vehicle (mineral oil)-treated group. Intramuscular pretreatment with 3
or 5% lidocaine reduced MO-induced hindpaw shaking behaviour and increases in
extravasated Evans' blue dye concentration. Intramuscular pretreatment with 5 mM
MCPG, non-selective group I/II mGluR antagonist, or MPEP, a selective group I
mGluR5 antagonist, produced a significant attenuation of MO-induced hindpaw
shaking behaviour and increases in extravasated Evans' blue dye concentration in
the masseter muscle while LY367385, a selective group I mGluR1 antagonist, did
not affect MO-induced nociceptive behaviour and inflammation in the masseter
muscle. These results indicate that peripheral mGluR5 plays important role in
mediating MO-induced nociceptive behaviour and inflammation in the craniofacial
muscle.
PMID- 17027774
TI - Olfactory deficit in idiopathic rapid eye movements sleep behavior disorder.
AB - INTRODUCTION: REM sleep behavior disorder (RBD) is a parasomnia characterized by
a loss of atonia and an increased phasic muscle activity during REM sleep.
Idiopathic RBD frequently herald an alpha-synucleinopathy, including such as
Parkinson's disease (PD) and dementia with Lewy Body (DLB). Pathological changes
in the anterior olfactory nucleus and olfactory loss occur very early in the
course of PD and DLB. The aim of the study was to assess olfactory function in a
large group of idiopathic RBD patients. METHODS: Fifty-four consecutive
polysomnographically-confirmed iRBD patients (44 men, 10 women; mean age: 69.2+/
8.3 years; mean Unified Parkinson's Disease Rating Scale Part III (UPDRS-III)
score: 4.9+/-4.3) and 54 age and gender-matched control subjects underwent the
Brief University of Pennsylvania Smell Identification Test (B-SIT). RESULTS: A
marked olfactory impairment was observed in the RBD group (mean B-SIT score:
7.1+/-2.5 versus 9.4+/-1.8; p < 0.0001), with 33 (61.1%) RBD patients versus 9
(16.6%) controls showing abnormal olfactory function (p < 0.0001). No correlation
was found between the degree of olfactory loss and either duration of RBD
symptoms or UPDRS-III score. Deficit in recognize paint thinner odorant showed
the highest positive predictive value (0.95) for identifying idiopathic RBD.
CONCLUSIONS: The olfactory deficit found in most idiopathic RBD patients shares
similarities with that described in PD and may be a sign of a widespread
neurodegenerative process. Its detection may help in identifying subjects at
higher risk of developing an alpha-synucleinopathy-mediated neurodegeneration.
PMID- 17027775
TI - Neuron theory, the cornerstone of neuroscience, on the centenary of the Nobel
Prize award to Santiago Ramon y Cajal.
AB - Exactly 100 years ago, the Nobel Prize for Physiology and Medicine was awarded to
Santiago Ramon y Cajal, "in recognition of his meritorious work on the structure
of the nervous system". Cajal's great contribution to the history of science is
undoubtedly the postulate of neuron theory. The present work makes a historical
analysis of the circumstances in which Cajal formulated his theory, considering
the authors and works that influenced his postulate, the difficulties he
encountered for its dissemination, and the way it finally became established. At
the time when Cajal began his neurohistological studies, in 1887, Gerlach's
reticular theory (a diffuse protoplasmic network of the grey matter of the nerve
centres), also defended by Golgi, prevailed among the scientific community. In
the first issue of the Revista Trimestral de Histologia Normal y Patologica (May,
1888), Cajal presented the definitive evidence underpinning neuron theory, thanks
to staining of the axon of the small, star-shaped cells of the molecular layer of
the cerebellum of birds, whose collaterals end up surrounding the Purkinje cell
bodies, in the form of baskets or nests. He thus demonstrated once and for all
that the relationship between nerve cells was not one of continuity, but rather
of contiguity. Neuron theory is one of the principal scientific conquests of the
20th century, and which has withstood, with scarcely any modifications, the
passage of more than a 100 years, being reaffirmed by new technologies, as the
electron microscopy. Today, no neuroscientific discipline could be understood
without recourse to the concept of neuronal individuality and nervous
transmission at a synaptic level, as basic units of the nervous system.
PMID- 17027776
TI - Nitric oxide synthase in retina and optic nerve head of rat with increased
intraocular pressure and effect of timolol.
AB - We investigated the expression of nitric oxide synthase (NOS) isoforms -1, -2 and
-3 in the retina and optic nerve head (ONH) in an experimental rat model of
elevated intraocular pressure (IOP) before and after treatment with timolol, to
assess whether its neuroprotective action is associated with the activity of
these enzymes. Episcleral vein cauterization in unilateral eyes of Wistar rats
was performed to produce elevated IOP. Histological sections of retina and ONH
from animals with normal IOP, with elevated IOP, and elevated IOP treated with
timolol, were studied by immunohistochemistry with antibodies to NOS-1, NOS-2,
and NOS-3. In the control rats, NOS-1 was localized to photoreceptor inner
segments, amacrine cells and bipolar cells in the retina, and in astrocytes,
pericytes and vascular nitrergic terminals in the ONH. NOS-3 immunostaining
localized to the endothelial cells. The rats with elevated IOP showed increased
expression of NOS-1 in the plexiform layers of the retina and reactive astrocytes
in the ONH. These cells also showed NOS-2 positivity. The rats treated with
timolol showed reduced expression of NOS-1 in the retina and ONH. NOS-2 was only
detected in a few groups of astrocytes in the ONH. NOS-3 was unchanged in both
elevated IOP and timolol-treated groups. These results show that excessive levels
of NO synthesized by the NOS-1 and -2 isoforms, considered neurotoxic, might
contribute to the progressive lesions of retinal ganglion cell axons. Their
reduction after treatment suggests a possible neuroprotective effect of timolol
in neurons exposed to excessive amounts of NO.
PMID- 17027777
TI - Antidepressant treatment reduces Fos-like immunoreactivity induced by swim stress
in different columns of the periaqueductal gray matter.
AB - Antidepressant treatment attenuates behavioral changes induced by uncontrollable
stress. The periaqueductal gray matter (PAG) is proposed to be a brain site
involved in the behavioral responses to uncontrollable stress and antidepressant
effects. The main goal of the present study was to investigate the effect of
antidepressant treatment on the pattern of neural activation of the PAG along its
mediolateral and rostrocaudal subregions after a forced swim stress episode. Male
Wistar rats were sub-acutely treated with desipramine (a selective noradrenaline
re-uptake blocker, three injections of 10 mg/kg in 24 h) or clomipramine (a non
selective serotonin and noradrenaline re-uptake blocker, three injections of 10
mg/kg in 24 h) and submitted to the forced swimming test (FST). Two hours after
the test their brain were removed for Fos immunohistochemistry. Fos-like
immunoreactivity (FLI) in rostral, intermediate and caudal portions of
dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral
(vlPAG) PAG were quantified by a computerized system. The FST session increased
FLI in most parts of the PAG. Previous treatment with desipramine or clomipramine
reduced FLI in all columns of the PAG. FLI in the PAG correlated positively with
to the immobility time and negatively with to climbing behavior scored during the
test. These results indicate that neurons in the PAG are activated by
uncontrollable stress. Moreover, inhibitory action of antidepressants on this
activity may be associated with the anti-immobility effects of these drugs in the
FST.
PMID- 17027778
TI - Acute methylphenidate treatments reduce sucrose intake in restricted-fed bingeing
rats.
AB - Recent evidence suggests that methylphenidate HCl may be effective at limiting
the frequency and the amount of binge eating. The present study investigated if
daily treatments with methylphenidate reduced the bingeing-like behavior observed
in restricted-fed adult male rats. Three groups (n = 6) received peripheral
injections of methylphenidate in doses of 1.5 or 0.75 mg/kg/day, or saline, 3
days prior and 7 days during a previously characterized intermittent feeding
regimen that results in a gradual increase of sucrose and food intake. The
higher, but not the lower, dose of methylphenidate reduced sucrose intake to an
asymptotic level starting after 3 days of the feeding protocol and concurrently
led to an increase in the intake of chow. The high dose methylphenidate group
also had two-fold lower plasma insulin levels compared with the saline-treated
animals at the time of sacrifice on the last day of the feeding regimen. Further
histological assays revealed that the methylphenidate treatments, irrespective of
the dose used, resulted in selectively higher dopamine transporter and D2-like
receptor labeled bindings in the shell region of the nucleus accumbens. These
results suggest that relatively low-dose methylphenidate treatments may be
effective for the management of binge eating by reducing the intake of palatable
foods and may not interfere with short-term regulation of energy balance. These
findings further support the notion that the mesoaccumbens dopamine system plays
an important role in restricted access-induced sucrose bingeing in this rat
model.
PMID- 17027779
TI - Perceptual contributions to problem solving: Chunk decomposition of Chinese
characters.
AB - Chunk decomposition is the decomposing of familiar patterns into their component
elements so that they can be regrouped in another meaningful manner. Such a
regrouping is sometimes critically required in problem solving because during
initial encoding the problem elements become automatically grouped into familiar
chunks and this may prohibit finding a novel or efficient solution to problems
[G. Knoblich, S. Ohlsson, H. Haider, D. Rhenius, Constraint relaxation and chunk
decomposition in insight problem solving, J. Exp. Psychol. Learn. Mem. Cogn. 25
(1999) 1534-1556]. In order to elucidate the brain mechanisms underlying the
process of chunk decomposition, we developed a task that uses Chinese character
as materials. Chinese characters are ideal examples of perceptual chunks. They
are composed of radicals, which in turn, are composed of strokes. Because
radicals are meaningful chunks themselves but strokes are not meaningful in
isolation, it is much easier to separate a character by its radicals than to
separate a character by its strokes. By comparing the stroke-level decomposition
and the radical-level decomposition, we observed activities in occipital,
frontal, and parietal lobes. Most importantly, during the moment of chunk
decomposition, we found the early visual cortex showed a tendency of negative
activation whereas the higher visual cortex showed a tendency of positive
activation. This suggests that in order to successfully decompose a chunk, the
higher visual areas must at least partly be 'disconnected' from the input
provided by early visual processing in order to allow simple features to be
rearranged into a different perceptual chunk. We conclude that early perceptual
processes can crucially affect thinking and problem solving.
PMID- 17027780
TI - Changes of K+ -Cl- cotransporter 2 (KCC2) and circuit activity in propofol
induced impairment of long-term potentiation in rat hippocampal slices.
AB - Enhancing inhibition via gamma-aminobutyric acid type A (GABA(A)) receptors
contributes to anesthetic-induced impairment of long-term potentiation (LTP) of
excitatory synaptic transmission, which may account for general anesthesia
associated memory impairment (amnesia). The neuron-specific K+ -Cl- cotransporter
2 (KCC2) is necessary for fast synaptic inhibition via maintaining the low
intracellular chloride concentration required for the hyperpolarizing actions of
GABA via GABA(A) receptors. To explore a possible role of KCC2-dependent
inhibition in anesthetic-induced impairment of LTP, we used field excitatory
postsynaptic potentials (fEPSP) recording and immunoblotting to study the effect
of propofol on LTP maintenance and KCC2 expression in CA1 region of rat
hippocampal slices. We found that propofol (30 microM) not only impaired LTP
expression but also prevented LTP-accompanied downregulation of KCC2 without
affecting the basal transmission of glutamatergic synapses. Moreover, the
recurrent inhibition in hippocampal slices was enhanced by propofol. These
propofol-induced effects were completely abolished by picrotoxin, a specific
GABA(A) receptor-chloride channel blocker. Thus, enhancement of GABAergic
inhibition and suppression of neuronal excitability may account for the sustained
expression of KCC2 and the impairment of LTP by propofol. Together, this study
supports a novel role for KCC2 in LTP expression and gives hints to a molecular
mechanism, by which anesthetics might cause impairment of LTP.
PMID- 17027781
TI - Respiratory drive in hindlimb motoneurones of the anaesthetized female cat.
AB - Anatomical studies have shown a monosynaptic projection from nucleus
retroambiguus (NRA) to semimembranosus (Sm) motor nucleus in female cats, which
is stronger in oestrus. Expiratory bulbospinal neurones are the best documented
functional cell type in the NRA. If these cells participate in this projection,
an expiratory drive would be expected in Sm motoneurones and this drive would be
expected to be stronger in oestrus. In anaesthetized, paralyzed,
ovariohysterectomized female cats, artificially ventilated to produce a strong
respiratory drive (as monitored by phrenic nerve discharges), intracellular
recordings were made from Sm motoneurones and from motoneurones in the
surrounding hindlimb motor nuclei that are outside the focus of the NRA
projection. The animals comprised two groups: either treated for 7 days with
oestradiol benzoate (oestrous) or untreated (non-oestrous). Central respiratory
drive potentials (CRDPs) were observed in most motoneurones of both groups, with
amplitudes larger for the oestrous than for the non-oestrous group (1.58+/-1.34
mV versus 0.89+/-0.79 mV, mean+/-S.D.). However, the CRDPs most often consisted
of a maximum depolarization in early expiration, which declined in late
expiration and into inspiration. This pattern is different from the incrementing
firing pattern of most expiratory bulbospinal neurones. The CRDPs in Sm and
semitendinosus motoneurones (located in the same motor column) were of similar
size and frequency to CRDPs in motoneurones outside that column. The hypothesis
that expiratory bulbospinal neurones are significantly involved in the projection
was rejected. Alternative sources and possible functional roles for the CRDPs are
discussed.
PMID- 17027782
TI - Induction of dopaminergic neurons from growth factor expanded neural
stem/progenitor cell cultures derived from human first trimester forebrain.
AB - Multipotent stem/progenitor cells derived from human first trimester forebrain
can be expanded as free-floating aggregates, so called neurospheres. These cells
can differentiate into neurons, astrocytes and oligodendrocytes. In vitro
differentiation protocols normally yield gamma-aminobutyric acid-immunoreactive
neurons, whereas only few tyrosine hydroxylase (TH) expressing neurons are found.
The present report describes conditions under which 4-10% of the cells in the
culture become TH immunoreactive (ir) neurons within 24h. Factors including
acidic fibroblast growth factor (aFGF) in combination with agents that increase
intracellular cyclic AMP and activate protein kinase C, in addition to a
substrate that promotes neuronal differentiation appear critical for efficient TH
induction. The cells remain THir after trypsinization and replating, even when
their subsequent culturing takes place in the absence of inducing factors.
Consistent with a dopaminergic phenotype, mRNAs encoding aromatic acid
decarboxylase, but not dopamine-beta-hydroxylase were detected by quantitative
real time RT-PCR. Ten weeks after the cells had been grafted into the striatum of
adult rats with unilateral nigrostriatal lesions, only very few of the surviving
human neurons expressed TH. Our data suggest that a significant proportion of
expandable human neural progenitors can differentiate into TH-expressing cells in
vitro and that they could be useful for drug and gene discovery. Additional
experiments, however, are required to improve the survival and phenotypic
stability of these cells before they can be considered useful for cell
replacement therapy in Parkinson's disease.
PMID- 17027783
TI - Hemodynamic retrieval intensity in hippocampus is decreased by pre-exposure to
autobiographic test items.
AB - The purpose of this experiment was to assess the effects of probe familiarity,
the consequences of having recently retrieved an autobiographic memory (AM), on
subsequent recall. This was accomplished by replicating an earlier imaging
experiment, using the same participants and memory probes. Subtractions between
sessions showed significant pre-exposure effects (i.e., drop in BOLD signal
intensity) in the prefrontal cortex, thalamus, cerebellum and other brain
structures. Further, region of interest (ROI) analysis illustrated a significant
decrease in neural activity in the hippocampus in both conditions. The results
are discussed in terms of the pre-scan interview technique, a method applied in
AM research to procure personal information. Although invaluable, we emphasize it
must be used with caution as it can result in a loss of power. The widespread use
of this method in AM research may explain why studies often fail to find evidence
of significant responding in the hippocampus in response to memory probes.
Alternatively, when activity in the hippocampus is reported, it often fails to
differentiate between recent and remote memories. This point is of particular
importance to the on-going consolidation debate, as it often centers on a failure
to detect an effect in the hippocampus in one or both conditions.
PMID- 17027784
TI - Partnerships and innovations.
PMID- 17027785
TI - Elbow capsulectomy for posttraumatic elbow stiffness.
AB - PURPOSE: To determine factors associated with diminished elbow function and upper
extremity-specific health status after elbow capsulectomy for posttraumatic
stiffness. METHODS: Forty-six adult patients with posttraumatic elbow stiffness
were evaluated an average of 48 months after open capsular excision. A second
capsular excision was performed in 9 patients (29%). Stepwise multiple linear
regression analysis was used to identify predictors of the American Shoulder and
Elbow Surgeons Elbow Score, the Mayo Elbow Performance Index, and the
Disabilities of the Arm, Shoulder, and Hand scores after all procedures. RESULTS:
The average improvement in ulnohumeral motion after the index surgery for
capsular release was 53 degrees . (The average flexion was 98 degrees .) The 9
patients who had subsequent repeat elbow contracture release gained an additional
24 degrees , leading to a final average flexion arc for the entire cohort of 103
degrees . Multiple linear regression identified the American Shoulder and Elbow
Surgeons pain score, persistent ulnar nerve dysfunction, and duration of follow
up evaluation after the initial capsular release as independent predictors of a
higher Disabilities of the Arm, Shoulder, and Hand questionnaire score; flexion
arc and pain score as independent predictors of the Mayo Elbow Performance Index;
and flexion arc, forearm arc, pain score, and persistent ulnar neuropathy as
independent predictors of the American Shoulder and Elbow Surgeons score.
CONCLUSIONS: Open elbow capsulectomy for posttraumatic elbow stiffness restores a
near-100 degrees flexion arc on average. Second elbow releases provide limited
additional motion in most patients. Final motion influences physician-based
rating scales but not patient-specific health status (Disabilities of the Arm,
Shoulder, and Hand questionnaire), which is dominated by pain and persistent
ulnar neuropathy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 17027786
TI - Anatomy of the coronoid process.
AB - PURPOSE: Coronoid injuries are classified according to the size of the coronoid
fracture. The purpose of this study was to provide a detailed anatomic
description of the coronoid process, with specific focus on the coronoid height,
the coronoid width, and the olecranon-coronoid angle. METHODS: Thirty-five
cadaveric arms were dissected. All soft tissue was removed and the ulna was
disarticulated from the humerus, radius, and the carpal bones. A 3-dimensional
digitizing system was used to locate 19 anatomic landmarks on each specimen. By
using the 3-dimensional coordinates of the landmarks, the coronoid heights,
proximal ulnar widths, and olecranon-coronoid angles were determined. RESULTS:
The coronoid height, with its base defined by the trough of the trochlear notch
and the slope change of the distal coronoid process, measured 15 mm and was 42%
of the ulnar height. The coronoid height, with its base defined by the transverse
groove of the sigmoid notch at the guiding ridge and the distal insertion of the
brachialis muscle, measured 15 mm and was 43% of the ulnar height. The olecranon
coronoid angle ranged between 33 degrees and 38 degrees . CONCLUSIONS: For
lateral radiographic classification of coronoid fractures, coronoid height is
best defined by the trough of the trochlear notch and the slope change of the
distal coronoid process. For anatomic studies, coronoid height is best defined by
the transverse groove of the sigmoid notch at the guiding ridge and the distal
insertion of the brachialis muscle. The olecranon-coronoid angle is best defined
by the angle formed by the lines from the olecranon tip through the coronoid tip
and through the slope change of the distal coronoid process. The coronoid anatomy
measurements reported in this study may help to improve coronoid fracture
classification.
PMID- 17027787
TI - Patterns of mRNA expression for matrix molecules and growth factors in flexor
tendon injury: differences in the regulation between tendon and tendon sheath.
AB - PURPOSE: Injuries to tendons, particularly flexor tendons, can lead to loss of
function after healing due to adhesion formation and other complications. The aim
of this study was to increase our understanding of the healing process in tendons
and tendon sheaths to develop methods to affect the healing process and improve
the outcome of tendon repair in the future. METHODS: In a rabbit model of flexor
tendon injury, tissues were harvested 3, 6, 12, and 24 days after surgery (n = 6
for each group). After RNA extraction, messenger RNA (mRNA) levels for relevant
genes in tendon and tendon sheaths were measured using the reverse transcription
polymerase chain reaction. Messenger RNA levels for a subset of relevant
molecules at different time points after injury were compared with those of
uninjured controls for tendons and tendon sheaths. RESULTS: Initially after
injury, there was a shift in collagen expression with a marked increase in type
III mRNA levels in both the tendon and tendon sheath, whereas those for collagen
I increased only in the sheath at later time points. Aggrecan and versican mRNA
levels were increased in both tissues, but temporal aspects of the changes were
different. The mRNA levels for biglycan and lumican were all upregulated
throughout the healing interval examined, whereas those for decorin were
significantly decreased throughout in the tendon more so than the sheath. The
mRNA levels for basic fibroblastic growth factor and transforming growth factor
beta were elevated after injury in the tendon but not in the sheath. In contrast,
mRNA levels for connective tissue growth factor were unaltered or decreased in
both tissues throughout the interval assessed. CONCLUSIONS: Healing after injury
to the rabbit flexor tendon and tendon sheath follow a reproducible pattern of
gene expression; however, the pattern in the tendon is very different from that
in the sheath. These findings indicate that interventions developed to improve
healing of these tissues will have to address these differences, because they
will likely affect the outcomes.
PMID- 17027788
TI - Revision of incompletely released trigger fingers by percutaneous release:
results and complications.
AB - PURPOSE: Percutaneous trigger digit release has been reported as a safe,
effective, and quick procedure, but most surgeons convert to an open method for
residual triggering after percutaneous release. This study evaluates the safety
and efficacy of repeated percutaneous release for patients who had residual
triggering after the initial percutaneous release. METHODS: Between January 2000
and December 2002, 31 patients with a mean age of 55 years had a repeat
percutaneous release to treat residual snapping or locking symptoms. Surgery was
performed in the physician's office using the tip of a 19-gauge needle mounted on
a 2-mL syringe. Patients received regular postoperative follow-up examinations at
1, 6, and 12 weeks after surgery, and at the last visit, they completed a
questionnaire regarding the duration of pain or swelling and when were they able
to return to normal work. RESULTS: Twenty-eight digits (90%) were completely free
of triggering. Three digits (10%) during follow-up evaluation had residual
snapping. Of these, 1 patient had repeated percutaneous release, which achieved
an excellent outcome; 1 patient favored an open-release technique, and 1 patient
refused further treatment. No complications were identified at the final follow
up examinations. Almost all patients returned to normal work within 3 days.
CONCLUSIONS: Percutaneous A1 pulley release is an effective, safe, and convenient
technique for the primary trigger finger and as a secondary procedure for
patients who have residual triggering after the initial surgical procedure. TYPE
OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 17027789
TI - Flexor tenosynovitis caused by Mycobacterium scrofulaceum: case report.
AB - Atypical hand infections with Mycobacterium species are uncommon, and
Mycobacterium scrofulaceum infections are rare. We present a case of flexor
tenosynovitis caused by M scrofulaceum in a 66-year-old man with hypertension and
diabetes.
PMID- 17027791
TI - Arthroscopic repair of peripheral triangular fibrocartilage complex tears with
suture welding: a technical report.
AB - This report presents a method of arthroscopic repair of the peripheral triangular
fibrocartilage complex tears that replaces traditional suture knots with
ultrasonic welding of sutures. This will help eliminate potential causes of ulnar
sided wrist discomfort during the postoperative period.
PMID- 17027790
TI - Monopolar radiofrequency energy application to the dorsal extensor tendon
apparatus in a canine model of tendon injury.
AB - PURPOSE: To evaluate the use of monopolar radiofrequency energy (MRFE) to shorten
stretched dorsal extensor tendon apparatus (DETA) tissues in a canine model.
METHODS: Eleven adult canine forelimbs were used in this in vitro investigation.
The DETA tissue was isolated between the metacarpophalangeal and proximal
interphalangeal joints in the third and fourth digits of each limb. Isolated
tissue was stretched in all but 2 of the digits (control group). After tissue
stretching, monopular radiofrequency energy (MRFE) was applied to 18 of the
digits at 1 of 3 temperatures: 50 degrees C, 60 degrees C, or 70 degrees C
(stretch-treatment group). Two digits were treated identically, but MRFE was not
applied (stretch-only group). Tissue length was measured before and after
stretching and after treatment. Percent stretch, percent shortening, and percent
original length were compared among the 3 stretch-treatment groups. All DETA
specimens were examined with light microscopy. RESULTS: Histologic changes were
apparent in the stretch-treatment and stretch-only specimens compared with
controls. Percent stretch was not significantly different between groups. Percent
shortening and percent original length were significantly lower and higher,
respectively, in the 50 degrees C group than in the 60 degrees C and 70 degrees C
stretch-treatment groups, which were not significantly different from each other.
There was a significant linear correspondence between percent shortening and
treatment temperature. CONCLUSIONS: The application of MRFE at a temperature of
60 degrees C and a power of 10 W appears to shorten stretched DETA tissue to
approximately the prestretched length in an in vitro canine model. Further
investigation is necessary to determine the effect of treatment on the tissue's
mechanical properties.
PMID- 17027792
TI - Comparison between high-resolution MRI with a microscopy coil and arthroscopy in
triangular fibrocartilage complex injury.
AB - PURPOSE: To determine whether high-resolution magnetic resonance imaging (MRI)
could detect injuries to the triangular fibrocartilage complex (TFCC). METHODS:
Eleven patients who showed both a positive sign during the ulnocarpal stress test
and tenderness at the distal end of the ulna had a high-resolution MRI using a 47
mm diameter microscopy coil. Six regions of the TFCC were investigated for
injury: the radial attachment, disc, ulnar attachment of the triangular
fibrocartilage (TFC), ulnotriquetral ligament, palmar radioulnar ligament (PRUL),
and dorsal radioulnar ligament (DRUL). Arthroscopy was performed subsequently on
each patient. RESULTS: For injuries to the radial attachment or the disc of the
TFC, a high-resolution MRI showed 100% sensitivity and 100% specificity compared
with arthroscopy. In 3 cases in which injury to the ulnar attachment of the TFC
was detected with MRI and examination showed a positive piano-key sign and distal
radioulnar joint instability, only 1 injury was confirmed with arthrotomy. For
MRI diagnosis of an ulnotriquetral ulnolunate attachment injury, the sensitivity
was 100% and the specificity was 70%; however, 3 cases had false-positive
results. Finally MRI had 100% sensitivity for detecting DRUL and PRUL injuries,
although specificities were 75% and 83%, respectively. With MRI there were 2
false-positive DRUL injury diagnoses and 1 false-positive PRUL injury diagnosis.
CONCLUSIONS: High-resolution MRI using a microscopy surface coil allowed
assessment of each TFCC component and showed a higher accuracy for diagnosing
injuries to the radial attachment and the disc of the TFC compared with previous
studies. High-resolution MRI, however, was not able to diagnose DRUL, PRUL, or
ulnolunate ligament injuries accurately. TYPE OF STUDY/LEVEL OF EVIDENCE:
Diagnostic III.
PMID- 17027793
TI - Trapeziectomy and intermetacarpal ligament reconstruction with the extensor carpi
radialis longus for osteoarthritis of the trapeziometacarpal joint: surgical
technique and long-term results.
AB - PURPOSE: To report the long-term results of excision of the trapezium and
intermetacarpal ligament reconstruction with the extensor carpi radialis longus
for thumb trapeziometacarpal osteoarthritis. METHODS: Fourteen women and 5 men
were retrospectively reviewed after an average of 9 years of follow-up
evaluation. Trapeziectomy was performed and the extensor carpi radialis longus
was harvested by a dorsoradial approach to reconstruct the intermetacarpal
ligament. All patients wore a below-elbow cast for 6 weeks. Each patient had
objective and subjective assessments. Thumb shortening was measured in follow-up
radiographs. RESULTS: At the final follow-up evaluation, 16 (84%) patients were
free of pain and 17 patients (89%) were satisfied with the results. Grip, key
strength, and pinch strength improved compared with preoperative values. The
trapezium space lost 14% of its height compared with preoperative values. Thumb
motion improved, and there were no cases of instability. CONCLUSIONS: Resection
arthroplasty of the trapezium with intermetacarpal ligament reconstruction with
the extensor carpi radialis longus is an effective procedure that permits motion
restoration and pain relief in the trapeziometacarpal joint in the long term
without affecting thumb stability. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
IV.
PMID- 17027794
TI - Overgrowth after radial shortening for Kienbock's disease in a teenager: case
report.
AB - A 16-year-old boy was treated by a radial-shortening procedure for symptomatic
stage IIIB Kienbock's disease with 4 mm negative ulnar variance. The osteotomy
corrected the ulnar variance to negative 1 mm after surgery, but further negative
ulnar variance of 9 mm occurred at follow-up evaluation as a result of radial
overgrowth. The functional outcome was excellent with remodeling of the lunate.
The possibility of overgrowth should be considered when contemplating a radial
shortening osteotomy for Kienbock's disease in skeletally immature patients.
PMID- 17027795
TI - In vivo elongation of the palmar and dorsal scapholunate interosseous ligament.
AB - PURPOSE: To investigate the elongation of the palmar and dorsal subregions of the
scapholunate interosseous ligament (SLIL) in healthy human subjects throughout a
complete range of wrist motion. METHODS: The 3-dimensional in vivo kinematics of
the scaphoid and lunate were determined in both wrists of 13 female and 13 male
volunteers from computed tomography volume images. For each wrist the palmar and
dorsal insertions of the SLIL were identified on reconstructed surface models of
the scaphoid and lunate. The interbone distances between the palmar and dorsal
sites were calculated for the neutral wrist position. Elongations were then
calculated after applying the 3-dimensional kinematics to the scaphoid and
lunate. A multiple linear regression model was used to determine if elongations
varied significantly as a function of wrist flexion/extension and radioulnar
deviation. RESULTS: From pure wrist extension to pure wrist flexion, the fibers
of the SLIL at the palmar insertion site increased significantly, from 29%
shortening to 27% elongation, and the dorsal insertion decreased from 26% to 4%
shortening with respect to the fiber lengths in the neutral position. From pure
radial deviation to pure ulnar deviation, the elongation of the palmar insertion
significantly decreased from 9% elongation to 21% shortening. There was no
notable change in dorsal elongation with wrist radioulnar deviation. The multiple
linear regression model predicted that there would be minimal elongation of the
palmar and dorsal fibers at the wrist position along the dart thrower's path from
radial extension to ulnar flexion. CONCLUSIONS: In vivo elongation of the palmar
and dorsal fibers of the SLIL varied with wrist position. The palmar fibers
lengthened and the dorsal fibers shortened with wrist flexion and the opposite
occurred with wrist extension. Scapholunate interosseous ligament elongation was
minimal as the wrist was positioned along the dart thrower's path.
PMID- 17027796
TI - The outcome of intra-articular distal radius fractures treated with fragment
specific fixation.
AB - PURPOSE: To assess the clinical, radiographic, and functional outcome of treating
intra-articular distal radius fractures with fragment-specific fixation. METHODS:
A retrospective review of 81 patients with 85 intra-articular distal radius
fractures who were treated with fragment-specific fixation was performed. Minimum
time to follow-up evaluation was 1 year, with a mean time of 32 months. The
immediate postoperative films were compared with those taken at the final follow
up evaluation. Radiographs of the uninjured wrist were also obtained at the final
follow-up evaluation for comparison. Patients were examined for wrist and finger
range of motion, deformity, and grip strength, and they completed a standard
Disabilities of the Arm, Shoulder, and Hand outcome survey. RESULTS: According to
Gartland and Werley scoring there were 61 excellent and 24 good results. Flexion
and extension of the surgically treated wrist at the final follow-up evaluation
averaged 85% and 91%, respectively, of the uninjured wrist; grip strength
averaged 92% compared with the uninjured side. The average Disabilities of the
Arm, Shoulder, and Hand outcome score for the injured wrist was 9. Sixty-two
percent of patients achieved a 100 degrees arc of flexion and extension and
normal forearm rotation by postoperative week 6. Radiographic alignment was
maintained between immediate postoperative and final follow-up films, and there
were no cases of symptomatic arthritis at the final follow-up evaluation.
CONCLUSIONS: Fragment-specific fixation is a reasonable alternative for treating
intra-articular fractures of the distal radius. At final follow-up evaluations,
patients had good to excellent results with respect to range of motion, grip
strength, radiographic alignment, and satisfaction scores. Stable fixation
allowed starting active and passive motion of the wrist without compromising
postoperative alignment. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 17027797
TI - Functional outcome of en bloc excision and osteoarticular allograft replacement
with the Sauve-Kapandji procedure for Campanacci grade 3 giant-cell tumor of the
distal radius.
AB - PURPOSE: Multiple options have been reported for reconstruction of Campanacci
grade 3 giant-cell tumor of the distal radius after resection. In 1990, the
senior author described an allograft reconstruction combined with a Sauve
Kapandji procedure after distal radius resection and reported preliminary results
in 3 patients. The purpose of this study was to assess with validated patient
outcome surveys the intermediate to long-term outcomes of all patients treated
with this surgery and to analyze their functional results and document tumor
control. METHODS: All cases of distal radius osteoarticular allograft combined
with the Sauve-Kapandji reconstruction for Campanacci grade 3 giant-cell tumors
performed from 1986 to 2000 by a single surgeon were evaluated by clinical and
radiologic examinations; the Disabilities of the Arm, Shoulder, and Hand
questionnaire; the Short Form-36; and Mayo Wrist scores. RESULTS: Nine
consecutive patients (7 women, 2 men) with an average age at follow-up evaluation
of 42 years and with a Campanacci grade 3 giant-cell tumor of the distal radius
formed the study population. Clinical follow-up time after reconstruction
averaged 7 years. Examination showed an average of 51 degrees of extension and 19
degrees of flexion of the wrist and 63 degrees of supination and 79 degrees of
pronation of the forearm. Grip strength measured in 5 patients averaged 23 kg.
The Disabilities of the Arm, Shoulder, and Hand questionnaire; the Short Form-36;
and the Mayo Wrist scores averaged 15, 72, and 73, respectively. These scores
indicate modest functional impact. No patient had tumor recurrence, metastases,
nonunion, or proximal ulna instability. CONCLUSIONS: En bloc resection of a
Campanacci grade 3 giant-cell tumor of the distal radius followed by
reconstruction with an osteoarticular allograft and a Sauve-Kapandji procedure
with autogenous bone graft results in a reasonable functional outcome at
intermediate to long-term follow-up evaluation. TYPE OF STUDY/LEVEL OF EVIDENCE:
Therapeutic IV.
PMID- 17027798
TI - Mini-screw fixation for the treatment of proximal interphalangeal joint dorsal
fracture-dislocations.
AB - PURPOSE: Surgical intervention may be necessary to treat unstable dorsal fracture
dislocations of the proximal interphalangeal (PIP) joint of the hand. One method
of stabilization is open reduction and internal fixation (ORIF). The purpose of
this study was to assess the outcomes of ORIF for unstable dorsal fracture
dislocations of the PIP joint using mini-screws via a volar approach. METHODS: A
retrospective chart review with clinical follow-up evaluation was performed on 9
patients who had ORIF for unstable dorsal fracture-dislocations of the PIP joint.
The fracture fragment(s) from the middle phalangeal base were reduced and secured
using mini-screws. RESULTS: A clinical evaluation was performed at an average of
42 months after surgery. The average arc of motion for the involved PIP joint was
70 degrees (range, 55 degrees -90 degrees ). The average PIP joint motion in the
2 patients with 1 fracture fragment was 85 degrees , and the average PIP joint
motion for the remaining 7 patients was 65 degrees . One joint was subluxated
with an intra-articular screw. Nine patients had an average flexion contracture
of 14 degrees . Seven patients had no pain, and 2 had pain only with heavy
activity. CONCLUSIONS: Open reduction and internal fixation of unstable dorsal
PIP joint fracture-dislocations using mini-screws can be considered if the
fracture fragment(s) can accommodate the screws. The procedure attempts to
restore the concave contour of the middle phalangeal base and permits early
protected range of motion. The procedure should be approached cautiously,
especially in the presence of comminution. Proximal interphalangeal joint range
of motion is usually compromised; 8 of our 9 joints had a residual flexion
contracture. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 17027799
TI - Radial collateral ligament injury of the index metacarpophalangeal joint: an
underreported but important injury.
AB - PURPOSE: To present the results of various treatment modalities based on injury
grade of radial collateral ligament (RCL) injuries to the index
metacarpophalangeal (MP) joint. METHODS: Fourteen patients were evaluated (4
male, 10 female) with RCL injuries to the index MP joint. We defined injuries as
Grade 1 (tenderness over RCL, no instability), grade 2 (laxity compared to the
contralateral digit with a definite endpoint), or grade 3 (laxity without
endpoint). Early presentation is defined as less than four weeks and late greater
than four weeks. RESULTS: The average follow up was 24 months. Grade I-II
injuries seen early (4 patients) treated with 4-6 weeks splinting had excellent
results (normal ROM, stable pinch, pain free). There were no Grade I-II injuries
seen late. Of Grade III injuries seen early (2 patients), attempted treatment in
a removable splint was unsuccessful secondary to patient noncompliance;
subsequently requiring primary repair of the collateral ligament which resulted
in good outcomes. No Grade III injury seen early had attempted treatment in a
cast. Eight patients presented late with Grade III injuries (4 elected for
surgical intervention, 4 for nonsurgical management) and all had fair or poor
outcomes. CONCLUSIONS: The significance of this injury remains underestimated and
requires a high index of suspicion. Stable injuries seen early should be treated
with prompt immobilization. Casting may be more effective than a removable
splint. Grade III injuries seen early could possibly be treated with cast
immobilization though close follow up is mandatory as surgical repair may be
necessary in the high demand hand. All Grade III injuries treated late yielded
fair to poor results requiring tendon reconstruction or fusion with significant
alteration in hand function.
PMID- 17027800
TI - Attitudes of hand surgeons, hand surgery patients, and the general public
regarding psychologic influences on illness.
AB - PURPOSE: Psychologic influences on illness are well recognized but infrequently
addressed in the interactions of hand surgeons and patients. This study assessed
the attitudes of hand surgery patients and hand surgeons regarding psychologic
influences on illness and compared their attitudes with those of the general
population. METHODS: An 8-question survey regarding participant's attitudes
toward psychologic influences on illness was given to the general public (people
waiting in an airport), patients presenting to a hand surgery practice, and
members of the American Society for Surgery of the Hand. RESULTS: A total of 474
surgeons, 85 patients, and 42 public participants completed the survey. There
were no notable differences between patients and the general public, but the
surgeons' attitudes were markedly different from both patients and the general
public with respect to 4 items: the surgeons underestimated the openness of
patients and the general public to discussing psychologic influences and
willingness to see a psychologist or psychiatrist; and they were more supportive
than the general public or patients regarding the opinion that the placebo effect
reflects the strong influence of psychologic factors in healing and that
psychologic stress often is expressed as a physical complaint. The distribution
of patient responses showed 2 subgroups with respect to the idea that psychologic
stress often is expressed as a physical complaint and with regard to willingness
to see a mental heath professional, reflecting that a subset of patients with a
hand illness may be resistant to these concepts. CONCLUSIONS: Hand surgery
patients and the general public are not as aware of the psychologic influences on
illness as are hand surgeons, but they are more willing to consider and discuss
psychologic factors-and even psychologic treatment-than their surgeons realize.
Surgeons' views may be colored by a few negative interactions with challenging
patients, but a dialogue with our patients regarding the influence of psychologic
issues on illness will be well received by most patients and may facilitate
recovery.
PMID- 17027801
TI - Hand span influences optimal grip span in male and female teenagers.
AB - PURPOSE: To determine if there is an optimal grip span for determining the
maximum handgrip strength in male and female teenagers, and if the optimal grip
span was related to hand span. If they are related then the second aim was to
derive a mathematic equation relating hand span and optimal grip span. METHODS:
One hundred healthy teenage boys (15.1 +/- 1.1 y) and 106 girls (15.4 +/- 1.3 y)
were evaluated (age range, 13-18 y). Each hand was randomly tested on 10
occasions using 5 different grip spans, allowing a 1-minute rest between
attempts. The hand span was measured from the tip of the thumb to the tip of the
small finger with the hand opened as wide as possible. RESULTS: The results
showed that an optimal grip span to determine the maximum handgrip strength was
identified for both genders, and the optimal grip span and hand span correlated
in both genders. CONCLUSIONS: The results suggest that there is an optimal grip
span to which the dynamometer should be adjusted when measuring handgrip strength
in teenagers. The optimal grip span was influenced by hand span in both genders.
For males the optimal grip span can be derived from the equation y = x/7.2 + 3.1
cm, and for females from the equation y = x/4 + 1.1 cm. where y is the optimal
grip span and x is the hand-span. These equations may improve the reliability and
accuracy of the results and may guide clinicians and researchers in selecting the
optimal grip span on the hand dynamometer when measuring handgrip strength in
teenagers.
PMID- 17027802
TI - Outcomes research in hand surgery: where have we been and where should we go?
AB - PURPOSE: The outcomes movement began in response to a national emphasis to
control cost and to limit geographic variation in medical services. The impact of
the outcomes movement on hand surgery research is unknown. We conducted a
systematic review of hand surgery studies to assess the past and current states
of outcomes research in this specialty. METHODS: A systematic review of hand
surgery outcomes studies was conducted in The Journal of Hand Surgery (American
and British volumes) from 1988 to 2004. A Medline search using the 11 Agency for
Healthcare Research and Quality categories of outcomes studies was performed.
Studies were rated for study design, data endpoints, and level of impact using
the Agency for Healthcare Research and Quality-designated impact levels. RESULTS:
A total of 2,236 studies were identified, and 1,188 were included in the
analysis. Most studies were rated as level 1 impact (N = 1,090, 92%), and a small
number of studies were level 4 impact (N = 98, 8%). Thirty-nine percent were
prospective and 45% (N = 529) were retrospective descriptive studies. Data
gathered in studies included objective clinical measures (N = 672, 57%), quality
of life (N = 374, 31%), morbidity (N = 401, 34%), subjective clinical measures (N
= 27, 16%), cost (N = 185, 2%), and mortality (N = 11, 1%). CONCLUSIONS: Our
systematic review of hand surgery outcomes studies found that much of the
research is confined to testing new or existing surgical techniques (level 1
impact). We found a small number of studies that did show improvement in patient
outcomes as a result of an intervention (level 4 impact). The future direction of
outcomes studies should consider the impact of the research goals to change
patient or physician behavior to enhance health parameters. More research on
economic analysis needs to be conducted in hand surgery to meet the national goal
of containing cost and improving the quality of health care.
PMID- 17027803
TI - Outcome after repair of the scapholunate interosseous ligament and dorsal
capsulodesis for dynamic scapholunate instability due to trauma.
AB - PURPOSE: To retrospectively assess outcomes in 17 patients treated with
scapholunate (SL) interosseous ligament repair and capsulodesis for dynamic SL
instability due to trauma. METHODS: A retrospective review of 17 consecutive
patients included clinical and radiographic examinations to determine outcome
after SL interosseous ligament repair and dorsal capsulodesis. The average age at
the time of surgery was 36 years, and the postoperative follow-up period averaged
66 months. Outcome measures included the Mayo wrist evaluation system and
Disabilities of the Arm, Shoulder, and Hand questionnaire scores. Pain complaints
were measured on a 10-point visual analog scale. RESULTS: Preoperative and
postoperative measurements, respectively, for all patients were obtained as
follows: SL gap, 2 versus 3 mm; stress views of the SL gap, 3 versus 4 mm; SL
angle, 49 degrees versus 54 degrees ; capitolunate angle, 4 degrees versus 7
degrees . Grip strength was 82% of the uninjured side at the final follow-up
evaluations. Pain averaged a 3 out of 10 before and after surgery. Surgery was
completed an average of 22 weeks from injury. Disabilities of the Arm, Shoulder,
and Hand questionnaire scores averaged 31, indicating wrist impairment. Three
patients developed degenerative changes noted on postoperative x-rays. When
patients were evaluated based on daily job requirements (strenuous vs
nonstrenuous) there were statistically significant differences. Nonstrenuous job
requirements had lower pain scores; better Disabilities of the Arm, Shoulder, and
Hand questionnaire scores; better Mayo outcomes; better grip strength; and
decreased SL gap on stress views. Flexion and extension of the wrist were better
in the nonstrenuous group but did not reach statistical significance.
CONCLUSIONS: Prior reports evaluating patients for SL ligament repair appeared to
be favorable in short-term (1- to 2-y) follow-up periods. In the present report,
for patients followed up for an average of 66 months after surgery, the results,
clinically and radiographically, appear to deteriorate in those who place high
demands on the wrists on a daily basis. Although the numbers in the present study
are small, they indicate that SL ligament repair with dorsal capsulodesis may
have a place for patients who have normal preoperative static unloaded x-rays and
sufficient ligament for repair and who do not place high demands on the wrists on
a daily basis. The ideal procedure for this difficult problem continues to remain
elusive. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 17027805
TI - Glomus tumors.
AB - Glomus tumors are rare vascular tumors that are found most commonly in the hand.
Although the tumors are benign, they can cause intense focal pain. Patients often
go undiagnosed or misdiagnosed for many years because the tumors are small,
usually not palpable, and have varying presentations. A combination of magnetic
resonance imaging and clinical examination is used to support the diagnosis.
Surgical excision normally provides complete pain relief. An awareness of the
diagnosis is critical to preventing an unnecessary delay in treatment.
PMID- 17027804
TI - Arthroscopic treatment of glenohumeral instability.
AB - Arthroscopic treatment of glenohumeral instability using modern suture anchor
techniques has reported recurrence rates equal to open techniques, even in high
demand contact athletes. Compared with open procedures, arthroscopic
stabilization leads to less morbidity and less stiffness, leading to improved
postoperative function, especially in overhead athletes. This article highlights
the technical aspects of arthroscopic treatment of anterior glenohumeral
instability.
PMID- 17027806
TI - Refinements in the technique for repair of the accessory nerve.
AB - Trapezius muscle palsy after accessory nerve injury leads to periscapular pain
and shoulder motion deficit. The results of accessory nerve repair generally are
good, but surgery is difficult. The difficulty consists of finding the nerve
stumps that are embedded in fat and scar tissue from previous surgeries or
injuries. Five patients with accessory nerve lesions had surgery and grafting of
the accessory nerve. We dissected the proximal stump of the accessory nerve
within the fibers of the sternocleidomastoid muscle and in the vicinity of the
greater auricular nerve. To achieve dissection of the distal nerve stump, the
deep cervical fascia was detached from the trapezius muscle 3 cm cephalad to the
clavicle. The detached fascia and the trapezius muscle were flipped similar to
book pages. The motor branches entering the trapezius muscle were visualized and
followed toward the accessory nerve. A sural nerve graft with a mean length of
6.6 cm was used for grafting. Uncomplicated identification of the nerve stumps
was possible in all patients. After accessory nerve grafting, pain and motion
consistently improved in all patients. The technique proposed here ensures
reliable and rapid identification of the divided stumps of the accessory nerve.
PMID- 17027807
TI - Aberrant nerve in limited open carpal tunnel release.
PMID- 17027809
TI - A comparative study of ulnar shortening osteotomy by the freehand technique
versus the Rayhack technique.
PMID- 17027810
TI - Comparative study of the whisky aroma profile based on headspace solid phase
microextraction using different fibre coatings.
AB - A dynamic headspace solid-phase microextraction (HS-SPME) and gas chromatography
coupled to ion trap mass spectrometry (GC-(IT)MS) method was developed and
applied for the qualitative determination of the volatile compounds present in
commercial whisky samples which alcoholic content was previously adjusted to 13%
(v/v). Headspace SPME experimental conditions, such as fibre coating, extraction
temperature and extraction time, were optimized in order to improve the
extraction process. Five different SPME fibres were used in this study, namely,
poly(dimethylsiloxane) (PDMS), poly(acrylate) (PA), Carboxen
poly(dimethylsiloxane) (CAR/PDMS), Carbowax-divinylbenzene (CW/DVB) and Carboxen
poly(dimethylsiloxane)-divinylbenzene (CAR/PDMS/DVB). The best results were
obtained using a 75 microm CAR/PDMS fibre during headspace extraction at 40
degrees C with stirring at 750 rpm for 60 min, after saturating the samples with
salt. The optimised methodology was then applied to investigate the volatile
composition profile of three Scotch whisky samples--Black Label, Ballantines and
Highland Clan. Approximately seventy volatile compounds were identified in the
these samples, pertaining at several chemical groups, mainly fatty acids ethyl
esters, higher alcohols, fatty acids, carbonyl compounds, monoterpenols, C13
norisoprenoids and some volatile phenols. The ethyl esters form an essential
group of aroma components in whisky, to which they confer a pleasant aroma, with
"fruity" odours. Qualitatively, the isoamyl acetate, with "banana" aroma, was the
most interesting. Quantitatively, significant components are ethyl esters of
caprilic, capric and lauric acids. The highest concentration of fatty acids, were
observed for caprilic and capric acids. From the higher alcohols the fusel oils
(3-methylbutan-1-ol and 2.phenyletanol) are the most important ones.
PMID- 17027811
TI - Confirmatory and quantitative analysis using experimental design for the
extraction and liquid chromatography-UV, liquid chromatography-mass spectrometry
and liquid chromatography-mass spectrometry/mass spectrometry determination of
quinolones in turkey muscle.
AB - The aim of this work is to established methods for determination of quinolones
(ciprofloxacin, danofloxacin, enrofloxacin, difloxacin and flumequine), regulated
by European Union, and sarafloxacin in turkey muscle. An experimental design has
been applied for the optimization of the factors that influence the extraction of
quinolones from turkey muscle in order to determine the experimental conditions
for their extraction with high recoveries. Liquid chromatography with ultraviolet
detection (LC-UV), liquid chromatography-mass spectrometry (LC-MS) and liquid
chromatography tandem mass spectrometry (LC-MS/MS) have been used for the
simultaneous quantification of quinolones antibiotics in turkey muscle. The
proposed methods have been validated according to the Food Drugs Administration
guideline and presents the limit of quantification below the maximum residue
limits established by the European Union for quinolones in turkey muscle. The
methods developed have been applied to quantification of enrofloxacin and its
main metabolite ciprofloxacin in samples of turkey muscle obtained from animals
treated with enrofloxacin.
PMID- 17027812
TI - A level set method for determining critical curvatures for drainage and
imbibition.
AB - An accurate description of the mechanics of pore level displacement of immiscible
fluids could significantly improve the predictions from pore network models of
capillary pressure-saturation curves, interfacial areas and relative permeability
in real porous media. If we assume quasi-static displacement, at constant
pressure and surface tension, pore scale interfaces are modeled as constant mean
curvature surfaces, which are not easy to calculate. Moreover, the extremely
irregular geometry of natural porous media makes it difficult to evaluate surface
curvature values and corresponding geometric configurations of two fluids.
Finally, accounting for the topological changes of the interface, such as
splitting or merging, is nontrivial. We apply the level set method for tracking
and propagating interfaces in order to robustly handle topological changes and to
obtain geometrically correct interfaces. We describe a simple but robust model
for determining critical curvatures for throat drainage and pore imbibition. The
model is set up for quasi-static displacements but it nevertheless captures both
reversible and irreversible behavior (Haines jump, pore body imbibition). The
pore scale grain boundary conditions are extracted from model porous media and
from imaged geometries in real rocks. The method gives quantitative agreement
with measurements and with other theories and computational approaches.
PMID- 17027813
TI - A new glance at ruthenium sorption mechanism on hydroxy, carbonate, and fluor
apatites: Analytical and structural studies.
AB - The sorption mechanism of Ru3+ ions on hydroxy (HAp), carbonate (CO3HAp), and
fluor apatites (FAp) has been studied in detail. Ru apatites were obtained by
reaction of the apatites with RuCl3 in aqueous solution. The structure and
composition of the ruthenium-modified apatites were studied by several
techniques: elemental analysis, XRD, EXAFS, IR, NMR, SEM-EDS, TEM, and thermal
analysis. The amount of Ru in the modified apatite varies from 7.8 to 10.5 wt%
and is not related to the initial composition or the specific surface area of the
apatite. The different characterization techniques show that in the Ru-modified
apatites Ru is surrounded by six oxygen atoms and do not contain any chlorine.
For Ru-HAp and Ru-CO3HAp the new phase is amorphous whereas it is crystalline for
FAp. The catalytic oxidation ability is higher for Ru-HAp and Ru-CO3HAp compared
to Ru-FAp apatite in the oxidation of benzylic alcohol.
PMID- 17027815
TI - New ways of measuring blood pressure.
PMID- 17027816
TI - Blood pressure variability and cardiovascular risk in treated hypertensive
patients.
AB - BACKGROUND: The independent prognostic value of blood pressure (BP) variability
in treated hypertension is not yet clear. We investigated the relationship
between BP variability, evaluated by noninvasive monitoring, and cardiovascular
outcome in treated hypertensive patients. METHODS: The occurrence of fatal and
nonfatal cardiovascular events was evaluated in 1472 treated patients. Subjects
with the standard deviation of daytime or night-time systolic BP below or above
the median of the population were classified as having low or high BP
variability. Specifically, 738 and 734 patients had low and high daytime BP
variability, respectively, and 739 and 733 subjects had low and high night-time
BP variability, respectively. RESULTS: During follow-up (4.88 +/- 2.9 years,
range 0.2-11.6 years) there were 119 events. The event rates per 100 patient
years in subjects with low and high BP variability according to daytime BP were
1.18 and 2.01, respectively, and in those with low and high BP variability
according to night-time BP were 1.2 and 2.05, respectively. Event-free survival
was significantly different between the low and high BP variability groups (P =
.006 for both daytime and night-time BP). However, after adjustment for other
covariates in a Cox multivariate analysis, the adverse prognostic relevance of
high BP variability was no longer detectable, whereas age, smoking habit, LDL
cholesterol, diabetes, previous events, LV hypertrophy, and daytime or night-time
systolic BP resulted independent predictors of risk. CONCLUSIONS: Increased BP
variability is associated with higher incidence of cardiovascular events, but
also with other relevant prognostic factors. Indeed, in multivariate analysis the
possible adverse prognostic impact of BP variability is no longer evident. Thus,
in treated hypertension, BP variability evaluated by noninvasive monitoring is
not an independent predictor of outcome.
PMID- 17027817
TI - Renal dysfunction predicts attenuation of ischemic heart disease mortality risk
from elevated glucose among treated hypertensive patients.
AB - BACKGROUND: Impaired fasting glucose (IFG) and renal dysfunction are recognized
as independent risk factors for adverse heart outcomes. This study examines the
interaction of renal dysfunction and IFG (>or=110 mg/dL) upon the risk of
ischemic heart disease (IHD) mortality among treated hypertensive subjects.
METHODS: Subjects were 9918 participants in a worksite-based antihypertensive
treatment program in New York City (1981 to 1999) with baseline estimated
glomerular filtration rate (GFR) >30 mL/min/1.73 m2 (estimated by Cockcroft and
Gault formula) observed for a mean follow-up of 9.6 +/- 5.0 years (range 0.5-20.0
years). Outcome events were IHD deaths (n = 337) ascertained from the National
Death Index. Cox proportional hazard models were constructed for the entire
cohort to assess the interaction and then stratified by moderate renal
dysfunction (MRD; GFR 60-30 mL/min/1.73 m2). Age and sex adjusted rates were
calculated within MRD and NKF-defined categories. Hazard ratios for IFG were
calculated within MRD strata. RESULTS: The interaction product term of MRD and
IFG significantly improved (P = .001) a Cox proportional hazard model after
adjusting for known cardiovascular risk factors. Among participants with GFR
>or=60 mL/min/1.73 m2 the IHD mortality hazard ratio for IFG was 1.47 (95% CI =
1.09-1.99; P = .012). Conversely, among participants with MRD, the IHD mortality
hazard ratio for IFG was 0.44 (95% CI = 0.21-0.94; P = .034). CONCLUSIONS: These
results suggest an attenuating effect modification of GFR on IHD mortality risk
associated with IFG among treated hypertensive subjects. Whether the observed
qualitative interaction is simply statistical or reflects a biological counter
regulatory mechanism requires additional study.
PMID- 17027818
TI - Effects of 24-h shift work in the emergency room on ambulatory blood pressure
monitoring values of medical residents.
AB - BACKGROUND: Medical residency is marked by long work hours and shift work. The
acute effects of these factors on the blood pressure (BP) of medical residents
have not been adequately evaluated. METHODS: A total of 61 medical residents
underwent to ambulatory blood pressure monitoring (ABPM) during a 24-h shift work
in the emergency room (ER) and during a common working day. RESULTS: Both mean 24
h systolic and diastolic BP (DBP) and mean diastolic BP readings during sleep
were higher during the 24-h shift work in the ER than during common working day
(117 v 113 mm Hg, P < .05; 73 v 69 mm Hg, P < .05; and 61 v 58 mm Hg, P < .05,
respectively). Abnormally high mean BP readings were more frequent during the 24
h shift work in the ER than in common working day (19 v 8, P < .05). Pressure
load, nocturnal BP fall and pulse pressure values were similar in these two
different working situations. CONCLUSION: Working in the ER on a 24-h shift leads
to abnormal BP behavior in medical residents, thus suggesting that this type of
work may be a risk factor for cardiovascular disease.
PMID- 17027819
TI - Rate of morning increase in blood pressure is elevated in hypertensives.
AB - BACKGROUND: We applied a new logistic curve fitting procedure to ambulatory blood
pressure (ABP) recordings to determine whether the rate of increase in systolic
(SBP), mean (MBP) and diastolic blood pressure (DBP) and heart rate (HR) in the
morning is related to the level of BP in subjects. METHODS: The rate of
transition in the morning and evening period was determined using a six-parameter
double-logistic equation applied to 528 ABP recordings from a cardiovascular risk
assessment clinic. Based on daytime BP (MBP, SBP, or DBP), the upper quartile
(UQ, n = 132) and lower quartile (LQ) were compared. RESULTS: Subjects in the UQ
of daytime MBP were hypertensive and showed greater day-night differences
compared to normotensive subjects in the LQ (29 +/- 1 mm Hg for MBP compared to
20 +/- 1 mm Hg). The rate of morning increase in SBP and DBP was 42% and 30%
greater in UQ subjects compared to the LQ subjects (P < .05). The rates of
evening decrease in all BPs were 69% to 84% greater in the subjects in the UQ.
Similar results were obtained if subjects were divided according to daytime SBP
or DBP. The rate of morning increase in MBP was correlated with daytime BP, but
not night-time or 24 h MBP. CONCLUSIONS: The rate of morning increase in BP is
greater in those subjects with the highest daytime BP. The exaggerated rate of
morning increase in BP in this group, which were all hypertensive, may also be
important for greater cardiovascular risk.
PMID- 17027820
TI - Exaggerated morning surge in blood pressure in hypertension.
PMID- 17027821
TI - Aortic augmentation index is inversely associated with cardiorespiratory fitness
in men without known coronary heart disease.
AB - BACKGROUND: We investigated whether the aortic augmentation index (AIx), a
measure of arterial wave reflection and stiffness, is associated with
cardiorespiratory fitness in men without known coronary heart disease (CHD).
METHODS: Asymptomatic men (n = 201, mean age 51 +/- 9.2 years) referred for a
screening exercise electrocardiogram (ECG) underwent applanation tonometry to
obtain radial artery pulse waveforms, and an ascending aortic pressure waveform
was derived by a transfer function. The AIx is the difference between the first
and second systolic peak of the ascending aortic pressure waveform, expressed as
a percentage of the pulse pressure. Cardiorespiratory fitness was assessed by
maximal oxygen consumption (VO2max mL/min/kg) during a symptom-limited graded
exercise test. Multivariable regression analyses were used to identify
significant independent determinants of AIx and of VO2 max. RESULTS: Diabetes was
present in 2.5% of subjects, 34.8% had history of smoking, and 29% were
hypertensive. Mean (+/- SD) AIx was 19.9% +/- 9.0% and mean VO(2 max) was 33.9 +/
6.4 mL/min/kg. In a multivariable linear regression model, AIx was positively
associated with age, hypertension, and history of smoking and inversely with
heart rate, height, and body mass index (BMI). The VO2 max was significantly
inversely related to AIx after adjustment for age, heart rate, height, and BMI (r
= -0.22, P = .002), after further adjustment for CHD risk factors (total
cholesterol, HDL-cholesterol, history of smoking, diabetes, hypertension) (P =
.006), and after additional adjustment for behavioral factors (physical activity
score, alcohol intake, and percent body fat) (P = .022). CONCLUSIONS: These
findings indicate that AIx, a measure of arterial wave reflection and stiffness,
is inversely associated with cardiorespiratory fitness in men without CHD.
PMID- 17027822
TI - Relationship of circulating biomarkers of inflammation and hemostasis with
preclinical atherosclerotic burden in nonsmoking hypercholesterolemic men.
AB - BACKGROUND: Relations of mediators of inflammation and hemostasis with
preclinical atherosclerosis have been poorly analyzed. The aim of this study was
to test potential associations of these blood markers with indicators of
cardiovascular risk and atherosclerotic burden in asymptomatic, nonsmoking,
hypercholesterolemic men. METHODS: A total of 87 men underwent cardiovascular
risk assessment by means of 10-year Framingham risk calculation (median 9%) and
atherosclerotic burden evaluation by means of ultrasonographic measurement of
common carotid intima-media thickness and assessment of atherosclerotic plaques
at three arterial sites (three-site plaques). RESULTS: Of the markers C-reactive
protein, tumor necrosis factor-alpha, interleukin-10, factor VIIc, fibrinogen,
plasminogen activator inhibitor-activator, soluble intercellular adhesion
molecule-1, soluble P-selectin (sP-selectin), and von Willebrand factor, only sP
selectin was positively and independently associated with high Framingham risk
score (>9%) (71.7 +/- 3.6 ng/mL, n = 33 v 59.6 +/- 2.8, n = 54; mean +/- SEM; P <
.05) and with three-site plaques (75.4 +/- 5.7 ng/mL, n = 14 v 62.0 +/- 2.5, n =
73; P < .05). After adjustment for all of the above markers and for
cardiovascular risk factors, odd ratios of having high Framingham risk and three
site plaques were 3.38 (1.43 to 10.21) and 5.23 (1.74 to 23.52) respectively, per
1-standard deviation increase in sP-selectin. CONCLUSIONS: These results confirm
that among several hemostasis and inflammation mediators, only sP-selectin blood
level was associated with preclinical atherosclerosis. It might confer to sP
selectin measurement a clinical usefulness for detecting and managing high
cardiovascular risk in primary prevention.
PMID- 17027823
TI - Physical activity duration, intensity, and arterial stiffening in postmenopausal
women.
AB - BACKGROUND: Aerobic exercise training is associated with lower central arterial
stiffness, but little information exists on the effects of physical activity
intensity or duration on central arterial stiffness. Using a cross-sectional and
interventional approach, we tested the hypothesis that both moderate and vigorous
physical activity reduce central arterial stiffness in postmenopausal women.
METHODS: Carotid arterial stiffness (via ultrasound and applanation tonometry)
and duration of physical activity at low, moderate, and vigorous intensities (via
electronic accelerometer) were measured in 103 apparently healthy sedentary or
recreationally active women 47 to 82 years of age. Moderate intensity physical
activity was defined as 4.0 to 6.0 metabolic equivalents (MET) in subjects aged
<65 years and as 3.0 to 5.0 MET in subjects >or=65 years. A subgroup of 17
sedentary subjects was randomly assigned to moderate (n = 8) or vigorous (n = 9)
intensity cycling exercise training (900 kcal/week, three to five sessions per
week, for 12 weeks). Carotid arterial stiffness was measured before and after
training. RESULTS: Carotid beta-stiffness index was significantly correlated with
the duration of moderate and vigorous intensity physical activity (r = -0.25 and
r = -0.22) even after adjustment for age, height, and mean BP. Carotid beta
stiffness index significantly decreased after moderate and vigorous intensity
cycling training. There were no significant group differences in the magnitude of
beta-stiffness index change even after adjustment for expected confounders (eg,
baseline beta-stiffness index, height, body mass index, heart rate, and post
training body mass, body mass index, and mean BP). CONCLUSIONS: These results
suggest that both moderate and vigorous physical activities have favorable
effects on central arterial stiffness in postmenopausal women.
PMID- 17027824
TI - The benefits of exercise for arterial stiffness.
PMID- 17027825
TI - Chronic effect of combined treatment with omapatrilat and adrenomedullin on the
progression of heart failure in rats.
AB - BACKGROUND: We and other investigators have reported that short- and long-term
treatment with adrenomedullin has beneficial effects in heart failure. This study
examined the effects of long-term treatment with a vasopeptidase inhibitor plus
adrenomedullin in a model of heart failure in rats and assessed potential
mechanisms of action. METHODS: Dahl salt-sensitive rats aged 11 weeks were
randomly divided into three groups: an omapatrilat group, an omapatrilat plus
adrenomedullin group, and an untreated group. The effects of these treatments
were evaluated after 7 weeks of treatment. RESULTS: Omapatrilat monotherapy
significantly improved left ventricular weight (LVW), blood pressure (BP), and
central hemodynamics as compared with the untreated group. Omapatrilat decreased
the gene expression levels of adrenomedullin and atrial natriuretic peptide (ANP)
in the left ventricle. In addition, omapatrilat decreased mRNA levels of
transforming growth factor-beta (TGF-beta), collagen I, collagen III, plasminogen
activator inhibitor-1 (PAI-1), and intercellular adhesion molecule-1 (ICAM-1) in
the left ventricle, and omapatrilat decreased perifibrosis score and myocyte area
histologically. Omapatrilat plus adrenomedullin further improved LVW, central
hemodynamics, and mRNA expression of TGF-beta, collagen I, collagen III, PAI-1,
and ICAM-1 without changing BP. Omapatrilat plus adrenomedullin further reduced
mRNA levels of ANP and adrenomedullin without altering levels of ANP or
adrenomedullin in plasma. Interestingly, omapatrilat slightly decreased mRNA
levels of subunits of NADPH oxidase, whereas omapatrilat plus adrenomedullin
further decreased these variables. CONCLUSIONS: Our results suggest that combined
treatment with adrenomedullin and omapatrilat may be a new strategy for the
management of heart failure, acting partly by inhibition of the extracellular
matrix gene, adhesion molecule, antifibrinolysis, and oxidative stress
production.
PMID- 17027826
TI - Left ventricular hypertrophy in patients with autonomic failure.
AB - BACKGROUND: In autonomic failure (AF), supine hypertension may predispose
patients to end-organ damage. The pathophysiology of hypertensive heart disease
in AF is not known. The aim of the present study was to evaluate the prevalence
and predisposing factors of left ventricular hypertrophy (LVH) in patients with
AF. METHODS: We studied 25 patients with AF (67 +/- 8 years); 80% were being
treated for orthostatic hypotension. Twenty patients with essential hypertension
(68 +/- 6 years) were considered as the control group. All subjects underwent
echocardiography for measurement of left ventricular mass (LVM). The patients
with AF underwent a 24-h BP monitoring and long-term blood pressure (BP)
variability was calculated as standard deviation (SD) of the average of the half
hour mean values. RESULTS: The LVM is comparable in patients with AF and
hypertensive controls (145 +/- 35 g/m2 v 127 +/- 32 g/m2, P = .07). The
proportion of patients with LVH is similar in both populations (AF 80%,
hypertensive 70%). The patients with AF were divided into two groups, with and
without LVH. The SDs are significantly higher in AF patients with LVH than in
those with normal LVM (SD 24-h systolic BP: 22 +/- 4 v 14 +/- 1 mm Hg, P = .001).
CONCLUSIONS: A high proportion of patients with AF show LVH. The LVM values are
comparable with those of patients with essential hypertension. The development of
LVH seems to depend on high BP variability, characteristic of AF patients.
Detection of LVH may help in the choice of treatment for orthostatic hypotension
and in the prevention of heart failure.
PMID- 17027827
TI - Serum uric acid is a determinant of metabolic syndrome in a population-based
study.
AB - BACKGROUND: Determination of serum uric acid concentrations and role in risk of
metabolic syndrome (MS) were investigated in 1877 participants in a cross
sectional population-based study including a brief follow-up. METHODS: The MS was
identified by modified criteria of the Adult Treatment Panel III, and coronary
heart disease (CHD) by clinical findings and Minnesota coding of resting
electrocardiograms. Uric acid concentrations were measured by the uricase method.
RESULTS: Metabolic syndrome was present in 39.1% of the cohort. Linear regression
analysis of uric acid levels in a model comprising 13 variables identified
gender, waist girth, total cholesterol (TC), alcohol usage, triglycerides, log C
reactive protein (CRP), and log gamma-glutamyl transferase (GGT), and in women
diuretic use and elevated blood pressure (BP), as significant independent
covariates whereby the largest contribution (1.6 mg/dL) was generated by waist
girth. Logistic regression analysis of serum uric acid for MS disclosed for the
top versus the bottom tertile an odds ratio (OR) of 1.89 (95% confidence interval
[CI]: 1.45-2.46) in men and women combined, after adjustment for sex, age, TC,
log CRP, log GGT, alcohol, and diuretic drug use, presence of diabetes/impaired
fasting glucose, elevated BP, and smoking status. This corresponded to an
increase by 35% in MS likelihood for each 1 SD uric acid increment. This rate
declined to a significant 15% by inclusion of waist girth into the model. The OR
of uric acid concentrations for prevalent and incident CHD, adjusted for age, MS,
smoking, and diuretic use, was not significant among women and only tended toward
significance in men. CONCLUSIONS: Abdominal obesity is the main determinant of
uric acid variance. An increment of 1 SD in serum uric acid levels are associated
in both sexes with a 35% higher MS likelihood, independent of 10 risk factors
related to MS. After adjustment for waist girth, a more modest but significant
likelihood persists, which suggests that serum uric acid is a determinant of MS.
PMID- 17027828
TI - Reviewer's perspective of the role of uric acid.
PMID- 17027829
TI - Evening-morning differences in blood pressure in sleep apnea syndrome: effect of
gender.
AB - BACKGROUND: Obstructive sleep apnea (OSA) is associated with hypertension. In the
current study we sought to determine whether the evening-morning differences in
blood pressure (BP) would correlate with the severity of OSA and whether there
are gender-related differences. METHODS: A total of 2009 consecutive patients
referred to sleep examination because of suspected sleep apnea were
retrospectively included. The patients comprised 1566 men, of whom 870 were
nonhypertensive (non-HT) and 696 hypertensive (HT) and 443 women, of whom 258
were non-HT and 185 HT. Four BP measurements, two in the evening and two in the
morning, were taken. The relationship between evening-morning differences in BP
and the number of apneas/hypopneas divided by hours of sleep (AHI) were analyzed
separately for HT and non-HT men and women. RESULTS: In men, increase in AHI was
associated with increase in morning BP, and the evening-morning difference for
both systolic and diastolic BP became negative. These trends were found to be
significant by linear regression analyses both for HT (for systolic BP, r = 0.75,
P < .05, for diastolic BP r = 0.96, P < .05) and non-HT patients (for systolic BP
r = 0.93, P < .05, for diastolic BP r = 0.94, P < .05). In women (unlike in men),
increasing AHI was not associated with a linear increase in the evening-morning
BP differences. None of the regression lines fitted to the data was significant.
CONCLUSIONS: Our results demonstrate that the evening to morning difference in BP
in men with OSA is linearly related to the severity of OSA, both in patients with
HT and in those with non-HT. These results may have practical relevance in
screening for patients with OSA and may have prognostic clinical value in
predicting future cardiovascular events.
PMID- 17027830
TI - The sympathetic drive after acute myocardial infarction in hypertensive patients.
AB - BACKGROUND: Sympathetic activation occurs in hypertension (HT) and after acute
myocardial infarction (AMI) and is related to greater cardiovascular risk. Also,
AMI in patients with HT (AMI-HT) carries greater risk than that in normal
subjects (AMI-NT). We therefore planned to determine whether the sympathetic
activation and its duration after AMI are greater in patients with antecedent HT
than in patients with normal arterial pressure (NT). METHODS: In 68 matched
subjects with uncomplicated AMI-HT (n = 17), AMI-NT (n = 17), HT (n = 17), and NT
(n = 17), we measured resting muscle sympathetic nerve activity (MSNA) as the
mean frequency of multiunit bursts (m-MSNA) and single units (s-MSNA). In AMI
groups data were obtained 2 to 4 days after AMI and then at 3-month intervals
until MSNA returned to levels found in HT and NT. RESULTS: The AMI-HT had greater
(at least P < 0.05; ANOVA) s-MSNA (99 +/- 3.5 impulses/100 cardiac beats) than
AMI-NT (84 +/- 2.8 impulses/100 cardiac beats). During follow up, s-MSNA
hyperactivity in AMI-HT was always greater than in AMI-NT, and returned to values
found in HT and NT (84 +/- 3.5 impulses/100 cardiac beats and 62 +/- 4.4
impulses/100 cardiac beats, respectively) 9 months after AMI. Similar results
were obtained for m-MSNA. CONCLUSIONS: AMI in hypertensives resulted in greater
MSNA levels lasting at least 6 months longer than AMI in normotensives. This
indicates that AMI further augmented the MSNA hyperactivity of HT and that this
could be one mechanism involved in the reported worse prognosis in AMI-HT.
PMID- 17027831
TI - Reviewer critique of the sympathetic drive after acute myocardial infarction in
hypertensive patients.
PMID- 17027832
TI - Antihypertensive agents have different ability to modulate arterial pressure and
heart rate variability in 2K1C rats.
AB - We examined the effect of chronic (15 days) administration of antihypertensive
agents, from different pharmacologic classes, on arterial pressure (AP) and heart
rate variability in two-kidney, one-clip hypertensive (2K1C) rats. The 2K1C rats
received by gavage one of the following: water, ramipril, losartan, atenolol,
amlodipine, or hydrochlorothiazide. Sham-operated normotensive rats received
water. After 15 days of treatment AP was continuously sampled from an indwelling
catheter in awake rats during a 2-h period and systolic AP and pulse interval
(PI) were submitted to autoregressive spectral analysis with oscillatory
components quantified in low (LF: 0.25 to 0.75 Hz) and high (HF: 0.75 to 3.0 Hz)
frequency bands. The AP measured by tail-cuff was 170 +/- 2 mm Hg in 2K1C and 131
+/- 3 mm Hg in normotensive rats. Pooled data indicated that all antihypertensive
agents reduced the AP of 2K1C rats to 127 +/- 2 mm Hg, whereas 2K1C rats treated
with water remained hypertensive (206 +/- 11 mm Hg). Variance of systolic AP was
found increased in 2K1C rats treated with water (34 +/- 2 mm Hg2), whereas 2K1C
rats treated with ramipril, atenolol, amlodipine, or hydrochlorothiazide
presented AP variance similar to normotensive rats (16 +/- 2 mm Hg2). Losartan
normalized AP of 2K1C rats but variance of systolic AP remained increased (34 +/-
7 mm Hg2). The 2K1C rats treated with water had increased LF of systolic AP,
whereas 2K1C rats treated with losartan showed higher LF of systolic AP and PI.
Atenolol presented lower LF and higher HF of PI. In conclusion, losartan
normalized AP but did not reduce AP variability, suggesting an autonomic
imbalance characterized by higher sympathetic modulation of the cardiovascular
system.
PMID- 17027833
TI - Beta2-adrenoceptor polymorphisms relate to obesity through blunted leptin
mediated sympathetic activation.
AB - BACKGROUND: Obesity is a growing public health problem. It has been reported that
beta2-adrenoceptor polymorphisms are associated with obesity. This study examines
the associations of beta2-adrenoceptor polymorphism with relationships between
plasma norepinephrine (NE) and leptin to evaluate further the mechanisms of
obesity. METHODS: In 329 normotensive (BP <140/90 mm Hg) men with a wide range of
BMI (17.0 to 36.5 kg/m2), we measured BMI, total body fat mass, waist-to-hip
ratio (W/H), BP, plasma NE, leptin, and the beta2-(Arg16Gly, Gln27Glu)
adrenoceptor polymorphisms. The subjects consisted of 206 nonobese (BMI <25
kg/m2) and 123 overweight or obese (BMI >or=25 kg/m2) men. RESULTS: Overweight or
obese subjects had a significantly higher frequency of Gly16 and Glu27 alleles
compared with nonobese subjects. The subjects carrying Gly16 or Glu27 alleles
regardless of BMI had greater total fat mass, W/H and plasma leptin compared with
those without the Gly16 or Glu27 alleles, indicating that Gly16 and Glu27 alleles
of the beta2-adrenoceptor gene are related to obesity and fat mass. Only in the
nonobese subjects who carried the Gly16 and Glu27 alleles was there a high plasma
NE level, but similar in overweight or obese subjects. To evaluate leptin
mediated sympathetic activation, we performed linear regression analyses between
plasma leptin and NE. In groups with and without the Gly16 or Glu27 alleles,
plasma leptin correlated with NE, but the slope in the group carrying the Gly16
or Glu27 allele was significantly lower than that without the Gly16 or Glu27.
CONCLUSIONS: The findings demonstrate a strong and significant association of the
Gly16 and Glu27 alleles with obesity. Lower slopes between leptin and NE in the
subjects carrying these beta2-adrenoceptor polymorphisms indirectly indicate a
blunted leptin-mediated sympathetic nerve activity. We propose that the beta2
adrenoceptor polymorphisms related to blunted leptin-mediated sympathetic
activation offers further proof for the mechanisms of obesity.
PMID- 17027835
TI - Interactions between melatonin and estrogen in the regulation of blood pressure
in women.
PMID- 17027836
TI - Hypertension, diuretics, and uric acid.
PMID- 17027837
TI - Vectorcardiographic lead systems for the characterization of atrial fibrillation.
AB - OBJECTIVE: The aim of the study was to design a vectorcardiographic lead system
dedicated to the analysis of atrial fibrillation (AF). METHODS: Body surface
potentials during AF were simulated by using a biophysical model of the human
atria and thorax. The XYZ components of the equivalent dipole were derived from
the Gabor-Nelson equations. These served as the gold standard while searching for
an optimal orthogonal lead system for the estimation of the heart vector while
using a limited number of electrode positions. Six electrode configurations and
their dedicated transfer matrices were tested by using 10 different episodes of
simulated AF and 25 different thorax geometries. RESULTS: Root-mean-square-based
relative estimation error of the vectorcardiogram using the Frank electrodes was
0.39. An adaptation of 4 of the 9 electrode locations of the standard
electrocardiogram, with 1 electrode moved to the back, reduced the error to 0.24.
CONCLUSION: The Frank lead system is suboptimal for estimating the equivalent
dipole components (VCG) during AF. Alternative electrode configurations should
include at least 1 electrode on the back.
PMID- 17027838
TI - ST-segment elevation: a common finding in severe hypercalcemia.
PMID- 17027839
TI - P-wave and QRS complex measurements in patients undergoing hemodialysis.
AB - Hemodialysis (HD) has been associated with an increase in the amplitude of QRS
complexes. Experience in a single patient with multiple measurements has shown
that HD leads also to augmentation of P-wave amplitude. The objective of this
investigation was to evaluate electrocardiogram (ECG) changes with HD in a cohort
of patients undergoing this procedure with particular emphasis on the P-wave and
QRS complex changes. The sum of amplitudes of P waves (OP) and QRS complexes
(OQRS) in millimeters in the 12 leads of the ECG, along with a host of other ECG
parameters, body weight, blood pressure, heart rate, electrolytes, and
hemoglobin/hematocrit were measured before and immediately after HD in 47
patients. Hemodialysis resulted in a loss of a mean of 3 kg of weight and an
increase in the SigmaP, SigmaQRS, mean QRS duration, maximum P-wave duration, and
P-wave duration measured in lead II, whereas the changes in mean P-wave and
corrected QT interval durations were not statistically significant. Percentage
change (Delta%) in SigmaP and SigmaQRS correlated poorly with Delta% in
electrolytes, hematocrit, blood pressure, heart rate, and weight. Values for
SigmaP and SigmaQRS vs weight were r = 0.105, P = .48 and r = 0.09, P = .51,
respectively. The Delta% in SigmaP correlated well with Delta% in SigmaQRS (r =
0.42, P = .003). Alterations in P-wave amplitudes and duration commensurate with
the ones affecting the corresponding QRS complexes occur in patients undergoing
HD and indicate that evaluation of measurements in serial ECGs should take this
into account. The mechanisms of these phenomena continue to be elusive, and
whether they represent cardiac and/or extracardiac influences has not as yet been
unraveled.
PMID- 17027840
TI - Assessment of QT-measurement accuracy using the 12-lead electrocardiogram derived
from EASI leads.
AB - The purpose of the present study is to assess QT-interval measurements from the
EASI 12-lead electrocardiogram (ECG) as compared with the standard 12-lead ECG.
The QT interval was automatically determined in simultaneously recorded standard
and EASI 12-lead ECGs, using a validated wavelet-based delineator. The agreement
between the 2 sets of measurements was quantified both on a lead-by-lead basis
and a multilead basis with global definitions of QRS onset and T-wave end. The
results show that the agreement between QT-interval measurements from the 2 lead
systems is acceptable, with negligible mean differences and with correlation
coefficients ranging from 0.91 to 0.98 depending on the lead studied. Although
the SD shows a clear dependence on the selected lead (ranging from 9.2 to 26.4
milliseconds), differences are within the accepted tolerances for automatic
delineation. In a few patients, large differences were found, mainly because of
changes in morphology present in both lead systems. QT intervals measured by the
multilead approach were considerably more stable than single-lead measurements
and resulted in a much better agreement between the 2 lead systems (correlation
coefficient, 0.98; QT difference, 1.1 +/- 9.8 milliseconds). Thus, the EASI 12
lead ECG may be used for reliable QT monitoring when the multilead delineation
approach is adopted.
PMID- 17027841
TI - Identification and characterisation of the dopamine receptor II from the cat flea
Ctenocephalides felis (CfDopRII).
AB - G protein-coupled receptors (GPCRs) represent a protein family with a wide range
of functions. Approximately 30% of human drug targets are GPCRs, illustrating
their pharmaceutical relevance. In contrast, the knowledge about invertebrate
GPCRs is limited and is mainly restricted to model organisms like Drosophila
melanogaster and Caenorhabditis elegans. Especially in ectoparasites like ticks
and fleas, only few GPCRs are characterised. From the cat flea Ctenocephalides
felis, a relevant parasite of cats and dogs, no GPCRs are known so far. Thus, we
performed a bioinformatic analysis of available insect GPCR sequences from the
honeybee Apis mellifera, the mosquito Anopheles gambiae, the fruit fly Drosophila
melanogaster and genomic sequences from insect species. Aim of this analysis was
the identification of highly conserved GPCRs in order to clone orthologs of these
candidates from Ctenocephalides felis. It was found that the dopamine receptor
family revealed highest conservation levels and thus was chosen for further
characterisation. In this work, the identification, full-length cloning and
functional expression of the first GPCR from Ctenocephalides felis, the dopamine
receptor II (CfDopRII), are described.
PMID- 17027842
TI - Endocrine control of TAG lipase in the fat body of the migratory locust, Locusta
migratoria.
AB - Aspects of the role and activation of the enzyme triacylglycerol lipase (TAG
lipase) in the fat body of the migratory locust Locusta migratoria were
investigated. TAG lipase is under the hormonal control of the three endogenous
adipokinetic peptides of the migratory locust, Locmi-AKH-I, Locmi-AKH-II and
Locmi-AKH-III. Injection of low doses (5-10 pmol) of each peptide causes an
increase in lipase activity. The activation of lipase is time dependent: an
elevated activity was recorded 15 min after injection of 10 pmol Locmi-AKH-I and
maximum activation was reached after 45-60 min. The activation of TAG lipase is
also dose-dependent. Doses of 2 pmol of each Locmi-AKH had no effect, whereas 5
pmol caused a significant activation. Maximum activation is reached with a dose
of 10 pmol. Analogues of the second messengers cAMP (cpt-cAMP) and IP(3) (F
IP(3)) both activate the enzyme glycogen phosphorylase whereas only cpt-cAMP, but
not F-IP(3), activates TAG lipase; cpt-cAMP elevates the lipid levels in the
haemolymph. Activation of lipase is specific to the three endogenous AKH
peptides: 5 pmol of the endogenous peptide Locmi-HrTH and 10 pmol of corazonin
failed to activate lipase. High doses of octopamine did not activate lipase nor
did they elevate the lipid concentration in the haemolymph. TAG lipase is
stimulated by flight activity but activation is slower than that of glycogen
phosphorylase: after 30 min of flight or after 5 min of flight plus 1h of
subsequent rest, activity of TAG lipase is increased, but not immediately after 5
min of flight. In contrast, glycogen phosphorylase is activated significantly
after 5 min of flight. These activation patterns of the two enzymes mirror-image
the concentration of their substrates in the haemolymph: there is a significant
decrease in the concentration of carbohydrates after 5 min of flight, whereas no
change of the concentration of lipids can be measured after such short time of
flight activity; however, a subsequent rest period of 1h is sufficient to
increase the lipid concentration.
PMID- 17027843
TI - Anopheles gambiae immune responses to Sephadex beads: involvement of anti
Plasmodium factors in regulating melanization.
AB - We have performed a global genome expression analysis of mosquito responses to CM
25 Sephadex beads and identified 27 regulated immune genes, including several
anti-Plasmodium factors and other components with likely roles in melanization.
Silencing of two bead injection responsive genes, TEP1 and LRIM1, which encode
proteins known to mediate Plasmodium killing, significantly compromised the
ability to melanize the beads. In contrast, silencing of two Plasmodium
protective c-type lectins, CTL4 and CTLMA2, did not affect bead melanization.
This data suggest that the anti-Plasmodium factors have dual functions, as
determinants of both Plasmodium killing and melanization of the parasite and
other foreign bodies, while the Plasmodium protective factors are specifically
utilized by the parasite for evasion of mosquito defense mechanisms.
PMID- 17027844
TI - Differential usage of two promoters of the Broad-Complex gene in the silkworm,
Bombyx mori.
AB - The Broad-Complex gene encodes one of the key regulators of the ecdysone signal
cascade. We previously isolated part of the genomic DNA and cDNAs of Broad
Complex in Bombyx mori (BmBR-C). Here, we report structures of the entire genomic
DNA and 5' untranslated region (5'-UTR) of the cDNAs. BmBR-C was found to span
about 158 kbp including 13 exons. In the 5'-UTR, additional alternatively spliced
exons were identified. The 5' ends of the cDNAs were mapped to two different
positions, the distal promoter (P(dist)) and proximal promoter (P(prox)),
separated by 86 kbp. Expression from these promoters was controlled
differentially. Semi-quantitative PCR using cDNAs from the carcass, silk glands
and fat body revealed that expression from P(prox) was changed moderately and
expression from P(dist) was weak and constant during the fourth ecdysis. At the
onset of pupation, expression from P(prox) was suppressed in all tissues, but
that from P(dist) was induced in the carcass and ASG. In the fat body, expression
from both promoters increased in the prepupal stage. A combination of promoters
differing in responsiveness to an ecdysone signal may serve to achieve a complex
regulation of downstream genes in reply to a simple hormonal signal.
PMID- 17027845
TI - Purification, characterization and molecular cloning of the major chitinase from
Tenebrio molitor larval midgut.
AB - Insect chitinases are involved in degradation of chitin from the exoskeleton
cuticle or from midgut peritrophic membrane during molts. cDNAs coding for insect
cuticular and gut chitinases were cloned, but only chitinases from moulting fluid
were purified and characterized. In this study the major digestive chitinase from
T. molitor midgut (TmChi) was purified to homogeneity, characterized and
sequenced after cDNA cloning. TmChi is secreted by midgut epithelial cells, has a
molecular weight of 44 kDa and is unstable in the presence of midgut proteinases.
TmChi shows strong substrate inhibition when acting on umbelliferyl-derivatives
of chitobio- and chitotriosaccharides, but has normal Michaelis kinetics with the
N-acetylglucosamine derivative as substrate. TmChi has very low activity against
colloidal chitin, but effectively converts oligosaccharides to shorter fragments.
The best substrate for TmChi is chitopentaose, with highest k(cat)/K(M) value.
Sequence analysis and chemical modification experiments showed that the TmChi
active site contains carboxylic groups and a tryptophane, which are known to be
important for catalysis in family 18 chitinases. Modification with p
hidroximercuribenzoate of a cysteine residue, which is exposed after substrate
binding, leads to complete inactivation of the enzyme. TmChi mRNA encodes a
signal peptide plus a protein with 37 kDa and high similarity with other insect
chitinases from family 18. Surprisingly, this gene does not encode the C-terminal
Ser-Thr-rich connector and chitin-binding domain normally present in chitinases.
The special features of TmChi probably result from its adaptation to digest
chitin-rich food without damaging the peritrophic membrane.
PMID- 17027847
TI - Active ammonia absorption in the midgut of the Tobacco hornworm Manduca sexta L.:
transport studies and mRNA expression analysis of a Rhesus-like ammonia
transporter.
AB - In this study the mid- and hindgut of Manduca sexta larvae were tested for their
ammonia transport properties using a custom-made Ussing chamber. In the presence
of 0.1 mmoll(-1) ammonia on both sides of the isolated epithelium, active
transepithelial ammonia absorption (aTEPA) was observed in all midgut sections,
with greatest transport rates (ca. 140 nmol cm(-2)h(-1)) detected in the median
midgut. The hindgut showed no aTEPA. In the median midgut inhibition of energy
metabolism by azide blocked aTEPA completely, whereas inhibition of vacuolar H(+)
ATPase by bafilomycin A(1) reduced the active transport by 50%. The imposition of
a luminal-directed NH(3)-gradient (pH 6.5 apical, pH 8.5 basal) lowered the aTEPA
by approximately 50% but did not reverse its direction. Apical addition of
amiloride reduced aTEPA by 90%, suggesting a role of carrier-mediated ammonia
transport across the apical membrane via a member of the NHE family. Inhibition
of the microtubule network by colchicine reduced aTEPA by ca. 50%. In contrast,
blocking basal K(+) channels by Ba(2+) had no effect on aTEPA. Using molecular
methods, evidence for intestinal expression of a Rhesus-like ammonia transporter
(RhMS) was found with low mRNA expression in midgut tissues, but high expression
levels in the hindgut, Malpighian tublules and ganglia.
PMID- 17027846
TI - Expression and down-regulation of cytochrome P450 genes of the CYP4 family by
ecdysteroid agonists in Spodoptera littoralis and Drosophila melanogaster.
AB - The function of CYP4 genes in insects is poorly understood. Some CYP genes are up
regulated by ecdysteroids and a number of Cyp4 genes in Drosophila melanogaster
have been shown by microarray to be down-regulated when the ecdysteroid titre is
high, suggesting hormonal regulation. Here, we report the utilization of certain
cloned CYP4 cDNAs/fragments to probe their developmental/tissue expression in the
Lepidopteran, Spodoptera littoralis, including the effects of ecdysteroid
receptor agonists (bis-acyl hydrazines). CYP4L8 is expressed essentially
throughout the final larval instar of S. littoralis and, together with CYP4M12,
is down-regulated by agonist. Furthermore, expression of these genes occurs in
midgut, but is undetectable in brain, fat body, and integument. Similarly, in D.
melanogaster, Cyp4ac1, Cyp4ac3, Cyp4ad1 and Cyp4d1 gene expression is drastically
down-regulated by ecdysteroid agonist. The significance of the results is
discussed in relation to the plausible functions of the CYP4 genes in Lepidoptera
and mechanisms of down-regulation.
PMID- 17027848
TI - Delta11 desaturases of Trichoplusia ni and Spodoptera littoralis exhibit dual
catalytic behaviour.
AB - The Delta(11) desaturases found in moths such as Spodoptera littoralis play a
critical role in the biosynthesis of their sex pheromones. The ability to
functionally express these enzymes in yeast has allowed one to study the
transformation of long-chain fatty acyl substrates to their 11-ene products in
greater mechanistic detail. In this article, we report on the detection and
quantitation of a minor 11-hydroxylated byproduct (0.1% of total fatty acids),
which is formed by the Delta(11) desaturases found in Trichoplusia ni and
Spodoptera littoralis. The position of the hydroxyl group was determined by
characteristic mass spectral fragmentation of the trimethylsilyl derivatives and
is in accord with predictions based on previous mechanistic investigations of the
Spodoptera Delta(11) desaturase. The level of 11-hydroxylation was insensitive to
the mode of desaturase expression (constitutive vs. induced) and the presence or
absence of a b5-fusion domain. Our findings suggest that in future, a search for
hydroxylated products should be included in functional analyses of insect
desaturase genes.
PMID- 17027849
TI - New flow cytometric technique for the evaluation of circulating endothelial
progenitor cell levels in various disease groups.
AB - Circulating endothelial progenitor cells (EPC) localise to sites of ischaemia and
play a role in vascular repair and re-endothelialisation of injured blood
vessels. Low levels of EPCs are associated with cardiovascular disease (CVD) in
the general population. It is not clear at present whether and how the numbers of
circulating EPCs vary in diseases other than CVD. We have enumerated EPCs by the
flow cytometric analysis of whole blood by using a novel cocktail of monoclonal
antibodies. This consisted of CD2FITC, CD13FITC and CD22FITC to eliminate non
progenitor cells and VEGFR2PE and CD133-streptavidin-PeCy7 to include only EPCs.
We analysed 250 patients with varying stages of uraemia, 36 patients with
inflammatory bowel disease (IBD) and 9 patients with acute respiratory distress
syndrome and compared this to 74 healthy controls. Using flow cytometry we were
able to measure the circulating levels of EPCs, with a result available within
hours of the sample being obtained. Circulating EPC numbers vary in different
patient groups and healthy controls. In uraemic patients, irrespective of disease
severity, there are lower numbers of circulating EPC numbers compared to normal
controls (46.6+/-3.7 vs. 66.1+/-4.7; p=0.03). This new technique provides a means
of monitoring patients and shows a reduction in circulating EPCs in uraemic
patients; this abnormality may be a target of novel therapies.
PMID- 17027850
TI - Antibody generation through B cell panning on antigen followed by in situ culture
and direct RT-PCR on cells harvested en masse from antigen-positive wells.
AB - We describe a method for the generation of high-affinity monoclonal antibodies,
which combines the power of natural immune responses with in vitro panning, B
cell culture, RT-PCR and expression of the recombinant product. B cells from
immunised rabbits were incubated at approximately 1000-10,000 cells per well with
solid phase antigen coated on the surface of 96-well ELISA plates. Extensive
washing removed non-binding cells as well as those B cells, which bound with low
affinity. Retained B cells were cultured for 7 days in the presence of activated
rabbit splenocyte supernatant and irradiated EL-4-B5 mouse thymoma cells, to
induce proliferation and secretion of immunoglobulin. Supernatants were screened
to confirm the presence of specific antibody, before the cells were harvested en
masse from individual positive wells. Single heavy- and light-chain variable
region genes were recovered from individual wells by RT-PCR, critically without
the need for isolation of single B cells. Paired VH and VL genes were
subsequently expressed as recombinant antibodies and shown to retain the original
activity and specificity of the B cell culture supernatants. The method has also
been successfully applied to the generation of high-affinity antibodies to
antigen expressed on the surface of target cells.
PMID- 17027852
TI - Dodecin sequesters FAD in closed conformation from the aqueous solution.
AB - Both extensive theoretical calculations and experimental data obtained during
several decades leave little doubt that flavin adenine dinucleotide (FAD) exists
in an open as well as in a closed conformation in aqueous solution. However, the
knowledge about the intramolecularly stacked complex of FAD is constructed on
indirect methods while direct structural evidence is lacking. Recently, dodecin
was reported as an unspecific flavin binding protein which exhibits the unique
binding mode of incorporating stacked dimers of flavins into a single binding
pocket. Here, we show that FAD is not bound in this manner, but in monomers of
intramolecularly stacked conformation. As resulting from the dodecin ligand
binding characteristic, this FAD stacked conformation suggests to be directly
sequestered from the aqueous solution and thus to be the first X-ray structural
view on a FAD solution-stacked form. Moreover, in extraordinary FAD binding,
dodecin serves as a model for studying bound monomeric (FAD) versus bound dimeric
(e.g. riboflavin) flavin properties.
PMID- 17027851
TI - Dyssynchronous (non-uniform) Ca2+ release in myocytes from streptozotocin-induced
diabetic rats.
AB - Using biochemical/pharmacological approaches, we previously showed that type 2
ryanodine receptors (RyR2) become dysfunctional in hearts of streptozotocin
induced type 1 diabetic rats. However, the functional consequence of this
observation remains incompletely understood. Here we use laser confocal
microscopy to investigate whether RyR2 dysfunction during diabetes alters evoked
and spontaneous Ca(2+) release from the sarcoplasmic reticulum (SR). After 7-8
weeks of diabetes, steady-state levels of RyR2 remain unchanged in hearts of male
Sprague-Dawley rats, but the number of functional receptors decreased by >37%.
Interestingly, residual functional RyR2 from diabetic rat hearts exhibited
increased sensitivity to Ca(2+) activation (EC(50activation) decreased from 80
microM to 40 microM, peak Ca(2+) activation decreased from 425 microM to 160
microM). When field stimulated, intracellular Ca(2+) release in diabetic
ventricular myocytes was dyssynchronous (non-uniform) and this was independent of
L-type Ca(2+) currents. Time to peak Ca(2+) increased 3.7-fold. Diabetic myocytes
also exhibited diastolic Ca(2+) release and 2-fold higher frequency of
spontaneous Ca(2+) sparks, albeit at a lower amplitude. The amplitude of caffeine
releasable Ca(2+) was also lower in diabetic myocytes. RyR2 from diabetic rat
hearts exhibited increased phosphorylation at Ser2809 and contained reduced
levels of FKBP12.6 (calstablin2). Collectively, these data suggest that RyR2
becomes leaky during diabetes and this defect may be responsible to the reduced
SR Ca(2+) load. Diastolic Ca(2+) release could also serve as a substrate for
delayed after-depolarizations, contributing to the increased incidence of
arrhythmias and sudden cardiac death in type 1 diabetes.
PMID- 17027853
TI - In silico approaches reveal the potential for DNA sequence-dependent histone
octamer affinity to influence chromatin structure in vivo.
AB - Nucleosome positioning signals embedded within the DNA sequence have the
potential to influence the detailed structure of the higher-order chromatin
fibre. In two previous studies of long stretches of DNA, encompassing the chicken
beta-globin and ovine beta-lactoglobulin genes, respectively, we mapped the
relative affinity of every site for the core histone octamer. In both cases a
periodic arrangement of the in vitro positioning sites suggests that they might
influence the folding of a nucleosome chain into higher-order structure; this
hypothesis was borne out in the case of the beta-lactoglobulin gene, where the
distribution of the in vitro positioning sites is related to the positions
nucleosomes actually occupy in sheep liver cells. Here, we have exploited the in
vitro nucleosome positioning datasets to simulate nucleosomal organisation using
in silico approaches. We use the high-resolution, quantitative positioning maps
to define a one-dimensional positioning energy lattice, which can be populated
with a defined number of nucleosomes. Monte Carlo techniques are employed to
simulate the behaviour of the model at equilibrium to produce a set of
configurations, which provide a probability-based occupancy map. Employing a
variety of techniques we show that the occupancy maps are a sensitive function of
the histone octamer density (nucleosome repeat length) and find that a minimal
change in this property can produce dramatic localised changes in structure.
Although simulations generally give rise to regular periodic nucleosomal
arrangements, they often show octamer density-dependent discontinuities, which
tend to co-localise with sequences that adopt distinctive chromatin structure in
vivo. Furthermore, the overall organisation of simulated chromatin structures are
more closely related to the situation in vivo than is the original in vitro
positioning data, particularly at a nucleosome density corresponding to the in
vivo state. Although our model is simplified, we argue that it provides a unique
insight into the influence that DNA sequence can have in determining chromatin
structure and could serve as a useful basis for the incorporation of other
parameters.
PMID- 17027854
TI - Imaging of the optic disc and retinal nerve fiber layer in acute optic neuritis.
AB - PURPOSE: To demonstrate whether optical coherence tomography (OCT-3) and scanning
laser ophthalmoscopy (HRT-2) can be used to measure changes of the optic disc and
peripapillary retinal nerve fiber layer (RNFL) in eyes with acute retrobulbar
optic neuritis that have no clinically apparent optic disc swelling. To correlate
these findings with presentation magnetic resonance imaging (MRI) of the affected
optic nerve. METHODS: Eight consecutive patients with acute retrobulbar optic
neuritis, who had no prior optic neuritis in either eye, were prospectively
investigated at presentation and at between 1 and 3 months with clinical
examination, OCT-3, HRT-2. At presentation, MRI of the optic nerves were
performed in 7/8 patients. RESULTS: Compared to unaffected eyes, affected eyes
without clinically seen optic disc swelling at baseline, there was a non
significant trend to increased thickness in the total RNFL, superior and nasal
measurements. Baseline HRT in affected eyes showed smaller mean cup to disc ratio
(p=0.003) and a smaller cup area (p=0.002) compared with the unaffected eye. The
MRI-demonstrated optic nerve lesion did not correlate with OCT RNFL thickening or
HRT decrease of the physiological cup. Follow-up imaging of the affected eyes
showed normalization of HRT cup size parameters and OCT RNFL thickness (p<0.04).
At follow-up, the temporal RNFL had thinning in 7/8 affected eyes (46.8 mum,
p=0.021) compared with fellow unaffected eyes (57.8 mum), which did not change.
CONCLUSION: OCT-3 and HRT demonstrate mild RNFL thickening or optic disc swelling
in acute optic neuritis, even when swelling is not seen clinically. OCT-3 appears
to reveal measurable RNFL thinning in the temporal quadrant after retrobulbar
optic neuritis, even though vision improves. RNFL imaging may be useful in future
studies of residual injury after optic neuritis.
PMID- 17027856
TI - Myotonic dystrophies type 1 and 2: a summary on current aspects.
AB - Myotonic dystrophies (DMs) encompass at least 2 forms: myotonic dystrophy type 1
and 2. In general, DMs are late-onset autosomal dominant disorders characterized
by a variety of multisystemic features including myotonia, muscular dystrophy,
cardiac conduction defects, dilated cardiomyopathy, posterior iridescent
cataracts, frontal balding, insulin-resistance and disease-specific serological
abnormalities such as gamma-glutamyltransferase and creatine kinase elevations,
hyperglycemia, hypotestosteronism, and reduced immunoglobulin (Ig) G and IgM
levels. Beyond the adult forms, in the classic DM1, a congenital form and an
early-onset form is recognized. Here we summarize current aspects of the myotonic
dystrophy pathogenesis and review the core features of both types of myotonic
dystrophies, including the congenital DM1.
PMID- 17027857
TI - Congenital muscular dystrophies and the extracellular matrix.
AB - During the past decade, considerable progress in the field of congenital muscular
dystrophies (CMDs) had led to the identification of a growing number of causative
genes. This genetic progress has uncovered crucial pathophysiological concepts
and has been instrumental in redefining clinical phenotypes. Important new
pathogenic mechanisms include the disorders of O-mannosyl-linked glycosylation of
alpha-dystroglycan as well as the involvement of a collagen type VI in the
pathogenesis of congenital disorders of muscle. Thus, an emerging theme among
gene products involved in the pathogenesis of congenital muscular dystrophy is
their intimate connection to the extracellular matrix. In this review, we focus
on the clinical phenotypes that we are correlating with the novel genetic and
biochemical findings encountered within CMD. This correlation will frequently
lead to a considerably expanded clinical spectrum associated with a given CMD
gene.
PMID- 17027858
TI - Autophagic vacuolar myopathy.
AB - Autophagic vacuoles are a frequent feature in numerous neuromuscular disorders.
However, they are also pathognomonic morphologic hallmarks in a slowly emerging
new group of conditions called autophagic vacuolar myopathies (AVMs), of which
Danon disease, originally called "lysosomal glycogen storage disease with normal
acid maltase," is the best known entity. Other such conditions, often although
not always described from Japan, are X-linked myopathy with excessive authophagy,
infantile autophagic vacuolar myopathy, adult-onset autophagic vacuolar myopathy
with multiorgan involvement, and X-linked congenital autophagic vacuolar
myopathy. Although only 1 protein, the transmembranous lysosomal protein LAMP-2,
has been found mutated in Danon disease, the remaining AVMs are genetically still
incompletely identified. Several of these conditions not only share autophagic
vacuoles, but such autophagic vacuoles also have morphologic properties of the
sarcolemma, thus rendering them autophagic vacuoles with sarcolemmal features, an
almost pathognomonic phenomenon of this group of disorders.
PMID- 17027859
TI - Protein aggregate myopathies.
AB - Protein aggregate myopathies (PAMs) based on the morphologic phenomenon of
aggregation of proteins within muscle fibers may occur in children
(selenoproteinopathies, actinopathies, and myosinopathies) or adults (certain
myofibrillar myopathies and myosinopathies). They may be mutation related, which
includes virtually all childhood forms but certain other forms as well, or
sporadic, which are largely seen in adults. Their classification as myofibrillar
or desmin-related myopathies, actinopathies, or myosinopathies is based on the
identification of respective mutant proteins, most of them components of the
sarcomeres. Recognition of PAM requires muscle biopsy and an extensive
immunohistochemical and electron microscopic workup of the biopsied muscle tissue
after which molecular analysis of morphologically ascertained proteins should
ensue to permit recognition of individual entities and genetic counseling of
patients and families. Because pathogenetic principles in PAMs are still
incompletely known, causative therapy, at this time, is not available.
PMID- 17027860
TI - The childhood limb-girdle muscular dystrophies.
AB - The heterogeneous childhood limb-girdle muscular dystrophies have originally been
defined as a group of autosomal recessive and dominant diseases with progressive
weakness and wasting of shoulder and pelvic-girdle muscles. Over the last 12
years, the underlying genetic defects for many of the diseases have been
identified and insight into pathomechanisms of disease has been gained. At the
same time, improved diagnostic techniques have allowed to extend the phenotypic
spectrum for many of these devastating conditions, which showed that clinical
symptoms and pathological findings are not restricted to skeletal muscles.
Childhood limb-girdle muscular dystrophies are systemic diseases that often
affect the musculoskeletal, respiratory, and cardiovascular system and that can
go along with central nervous system involvement and gastrointestinal symptoms.
The systemic nature of the diseases requires adequate management strategies that
improve symptoms, longevity, and quality of life of the patients. As we are
entering an era of translational research the need for precise molecular
diagnoses, a thorough understanding of the natural history of the diseases and
guidelines for standardized assessments of the patients become even more
relevant. In this review, the best characterized childhood limb-girdle muscular
dystrophies are discussed and their management aspects highlighted.
PMID- 17027861
TI - Glycogen storage disease: clinical, biochemical, and molecular heterogeneity.
AB - Glycogen storage diseases (GSDs) are characterized by abnormal inherited glycogen
metabolism in the liver, muscle, and brain and divided into types 0 to X. GSD
type I, glucose 6-phosphatase system, has types Ia, Ib, Ic, and Id, glucose 6
phosphatase, glucose 6-phosphate translocase, pyrophosphate translocase, and
glucose translocase deficiencies, respectively. GSD type II is caused by
defective lysosomal alpha-glucosidase (GAA), subdivided into 4 onset forms. GSD
type III, amylo-1,6-glucosidase deficiency, is subdivided into 6 forms. GSD type
IV, Andersen disease or amylopectinosis, is caused by deficiency of the glycogen
branching enzyme in numerous forms. GSD type V, McArdle disease or muscle
phosphorylase deficiency, is divided into 2 forms. GSD type VI is characterized
by liver phosphorylase deficiency. GSD type VII, phosphofructokinase deficiency,
has 2 subtypes. GSD types VIa, VIII, IX, or X are supposedly caused by tissue
specific phosphorylase kinase deficiency. GSD type 0, glycogen synthase
deficiency, is divided into 2 subtypes.
PMID- 17027862
TI - Spinal muscular atrophy: from gene to therapy.
AB - The molecular basis of spinal muscular atrophy (SMA), an autosomal recessive
neuromuscular disorder, is the homozygous loss of the survival motor neuron gene
1 (SMN1). A nearly identical copy of the SMN1 gene, called SMN2, modulates the
disease severity. The functional difference between both genes is a
translationally silent mutation that, however, disrupts an exonic splicing
enhancer causing exon 7 skipping in most SMN2 transcripts. Only 10% of SMN2
transcripts encode functional full-length protein identical to SMN1.
Transcriptional activation, facilitation of correct SMN2 splicing, or
stabilization of the protein are considered as strategies for SMA therapy. Among
various drugs, histone deacetylase inhibitors such as valproic acid (VPA) or 4
phenylbutyrate (PBA) have been shown to increase SMN2-derived RNA and protein
levels. Recently, in vivo activation of the SMN gene was shown in VPA-treated SMA
patients and carriers. Clinical trials are underway to investigate the effect of
VPA and PBA on motor function in SMA patients.
PMID- 17027863
TI - "My son is still walking": stages of receptivity to discussions of advance care
planning among parents of sons with Duchenne muscular dystrophy.
AB - Duchenne muscular dystrophy is an inherited progressive neuromuscular disease
that generally results in death by early adulthood. Because of its life
threatening nature, discussions of advance care planning are extremely relevant
to families with affected children and adolescents. Seventeen parents of sons
with Duchenne muscular dystrophy were interviewed about their attitudes,
experiences, and the nature of their discussions about these topics. Parents
showed a lack of familiarity with and experience communicating about advance care
planning. They also discussed opportunities for communication that centered on
transitional life events. Parents appeared to vacillate between hope for future
treatments, avoidance of emotionally difficult aspects of the disease, and
presence with the fullness of life's experiences. These data suggest a model for
future research in which windows of opportunity for discussion may exist as sons
are approaching significant transitional milestones and parents are able to see
the world through a lens of "presence."
PMID- 17027864
TI - Anti-leukemic activities of Dictyostelium secondary metabolites: a novel aromatic
metabolite, 4-methyl-5-n-pentylbenzene-1,3-diol, isolated from Dictyostelium
mucoroides suppresses cell growth in human leukemia K562 and HL-60 cells.
AB - It has previously been shown that DIF-1, a differentiation-inducing factor of the
cellular slime mold Dictyostelium discoideum, possesses antitumor activities in
mammalian tumor cells and that neuronal differentiation of PC12 cells can be
induced with furanodictines (FDs), aminosugar analogs found in D. discoideum, or
dictyoglucosamines (DGs), N-acetyl glucosamine derivatives (DG-A from D.
purpureum and DG-B from D. discoideum). Thus, cellular slime molds are attractive
natural resources that may provide valuable lead compounds to be utilized in the
field of pharmacology and medicine. In this study, we have isolated a novel
aromatic compound, 4-methyl-5-n-pentylbenzene-1,3-diol (MPBD), from fruiting
bodies of the cellular slime mold D. mucoroides and assessed the in vitro
antiproliferative activities of MPBD, FDs, and DGs in human leukemia K562 and HL
60 cells. MPBD at 20-80 microM dose-dependently suppressed cell growth in both
K562 and HL-60 cells. While FDs at 10-80 microM did not affect cell growth, DGs
at 10-40 microM dose-dependently suppressed cell growth in the cells. Although we
failed to find the roles of FDs and DGs in the original organisms, MPBD at 5-20
microM was found to promote stalk cell formation in D. discoideum. The present
results indicate that MPBD, DGs or their derivatives may have therapeutic
potential in the treatment of cancer and confirm our expectations regarding
cellular slime molds as drug resources.
PMID- 17027865
TI - Acute exposure to UVB has a more profound effect on plant genome stability than
chronic exposure.
AB - Environmental factors that damage DNA have various lengths of exposure and
intensity levels. Although the results of increasing the intensity of a DNA
damaging agent is often predictable, it is not clear whether the stage during
development when the exposure is received has any influence on the amount of DNA
damage. In this paper we analyzed the influence of UVB on the stability of
Arabidopsis thaliana and the Nicotiana tabacum genomes. Our experiments showed
that the acute exposure to UVB produces a significantly greater increase in
homologous recombination frequency (HRF) and recombination rate (RR) compared
with that produced by chronic exposure. The increase in HRF showed a positive
correlation with UVB dose and a negative correlation with plant age. In other
words, as the UVB dose was increased, there was a concomitant increase in HRF.
Conversely, older plants had a lower HRF increase as compared to younger plants.
Our experiments suggest that exposure to UVB makes the most significant impact on
genome stability during the early stages of plant development.
PMID- 17027866
TI - Amygdala control of emotion-induced forgetting and remembering: evidence from
Urbach-Wiethe disease.
AB - When presented in a neutral context, emotional items interfere with episodic
encoding of temporally contiguous non-emotional items, resulting in dissociable
valence-dependent retrograde and arousal-dependent anterograde modulatory
effects. By studying two rare patients with congenital lipoid proteinosis (Urbach
Wiethe) and a focal disease emphasis on the basolateral amygdala (BLA), we
demonstrate that this bidirectional modification of episodic encoding by emotion
depends on the integrity of the amygdala, as both retrograde and anterograde
modulatory effects are absent. Our findings implicate the amygdala in a neural
circuitry that orchestrates rapid retrograde and anterograde regulation of
episodic memory access upon criteria of behavioral significance.
PMID- 17027867
TI - Decomposition of extremely hard-to-degrade animal proteins by thermophilic
bacteria.
AB - Hard-to-degrade animal proteins are ubiquitously present throughout animal
bodies. Enormous numbers of these proteins generated in the meat industry are
converted to industrial wastes, the disposal of which is tremendously difficult.
Most hard-to-degrade animal proteins are currently disposed of by incineration;
however, this method has ecological disadvantages in terms of an apparent energy
loss and the production of a large amount of carbon dioxide. As a result, an
innovative solution to these problems has been sought. In this review, we focus
on the degradation of three hard-to-degrade animal proteins (extracellular matrix
proteins, collagen in particular, keratin, and prion proteins) and discuss the
decomposing capability of thermophilic bacteria. These proteins are strongly
resistant to proteinases because of their structural features; therefore, new
approaches employing bacterial proteases with strong activity and broad
specificity are required for practical application.
PMID- 17027868
TI - Purification and characterization of an alkaline lipase from Pseudomonas
aeruginosa isolated from putrid mineral cutting oil as component of metalworking
fluid.
AB - Extracellular lipase was isolated and purified from the culture broth of
Pseudomonas aeruginosa, an extremophile which naturally grows in water-soluble
mineral cutting oil (pH 10) used as metalworking fluid (MWF) for cooling and
lubrication in industrial metalworking processes. The molecular mass of the
purified lipase was estimated by SDS-PAGE to be 54 kDa. The optimum pH and
temperature were 11 and 70 degrees C, respectively. The enzyme is stabile over a
broad pH range (pH 4-11.5). The lipase preferably acted on triacylglycerols with
medium-chain fatty acids. The lipase was inhibited strongly by Zn(2+), Hg(2+),
Cu(2+) and slightly by Ca(2+) and Mg(2+). Non-ionic detergents and
sodiumdeoxycholate enhanced lipase activity. Alkaline lipase from P. aeruginosa,
capable of growing in a water-restricted medium has excellent properties and good
potential for biotechnological applications in the metal industry. Its marked
stability and activity in organic solvents suggest that this lipase is highly
suitable as a biotechnological tool in a water-restricted medium with a variety
of applications including organosynthetic reactions and the control and
prevention of MWF putrification in the metal industry.
PMID- 17027869
TI - Highly sensitive real-time PCR assay for quantification of toxic cyanobacteria
based on microcystin synthetase A gene.
AB - The presence of cyanobacterial bloom in water supply reservoirs can cause
potential health hazards. In this study, we aimed at the quantification of
microcystin-producing cyanobacteria based on the microcystin synthetase A (mcyA)
gene using real-time PCR. To perform a highly sensitive real-time PCR assay, the
novel primer MSR-2R was designed and a coprecipitation DNA extraction method was
used in this study. Cyanobacterial cells could be collected efficiently by
coprecipitation with other bacteria suspended in solution even in the case of low
concentrations of cyanobacteria. The detection limit of the method was found to
be 8.8 cells per reaction. When cyanobacterial growth was monitored in pure
culture, the cell concentration determined by real-time PCR positively correlated
with the cell concentration determined from direct microscopic count.
Furthermore, we could detect and quantify the mcyA gene in lake water samples
using real-time PCR. It was concluded that the quantification of the mcyA gene
based on real-time PCR is a powerful tool for the rapid quantification of
microcystin-producing cyanobacteria in environmental samples.
PMID- 17027870
TI - Effective utilization of transmitted light for astaxanthin production by
Haematococcus pluvialis.
AB - A new cultivation method, in which physiological responses of Haematococcus
pluvialis to different intensities and wavelengths of illuminating light are
utilized, is proposed. In this method, light transmitted through a cultivation
vessel illuminated from the opposite side was utilized for the early-phase
cultivation of H. pluvialis in another inoculated vessel that was located behind
the cultivation vessel, to save time required for the growth of cells. After
harvesting cells from the front vessel, the vessel that was originally behind was
shifted to the position of the front vessel. The abrupt increase in light
intensity caused by shift of the position induced the effective accumulation of
astaxanthin. These procedures for inoculation, shift of vessels and harvest were
repeated using two vessels arranged in series along the light path. After four
repeated cycles of cultivation (840 h from the start of cultivation), using 2.5
cm thick vessels, astaxanthin production per unit volume and the astaxanthin
content were higher than obtained in a batch cultivation with two 2.5 cm vessels.
PMID- 17027871
TI - High-efficiency secretory production of peroxidase C1a using vesicular transport
engineering in transgenic tobacco.
AB - Horseradish peroxidase isozyme C1a (HRP C1a) is widely used as a reporter enzyme
in a variety of detection procedures such as enzyme-linked immunosorbent assay
(ELISA) and western blotting. We previously isolated the gene encoding HRP C1a
and showed that HRP C1a is at first translated as a preproprotein containing
propeptides at its N- and C-termini (N-terminal secretion signal peptide and C
terminal propeptide; CTPP). The signal peptide (sp) is necessary for endoplasmic
reticulum (ER) translocation and the CTPP acts as a vacuolar sorting determinant.
Furthermore, HRP C1a was secreted into the culture medium from cells expressing
the HRP C1a gene without the CTPP region. We optimized the secretory production
system of HRP C1a in tobacco plants. To determine a suitable signal peptide for
high-efficient secretion of proteins, three types of sp derived from HRP C1a
(C1Psp), beta-D-glucan exohydrolase (GEsp) and 38 kDa peroxidase (38Psp) were
compared. GE and 38P are secretory proteins highly accumulated in the culture
medium of BY2 cells. The secretion efficiency was increased by 34% and 53% when
GEsp and 38Psp was used, respectively. Next, we used a translational enhancer,
the 5'-untranslated region of Nicotiana tabacum alcohol dehydrogenase gene (NtADH
5'-UTR). The production of HRP C1a was increased by placing NtADH 5'UTR in front
of the ORF in BY2 cells. These results indicate that the localization and
expression level of recombinant proteins can be controlled by the use of
propeptides and 5'UTR, respectively. Finally, high-efficiency secretory
production of the HRP C1a was also achieved in transgenic tobacco.
PMID- 17027872
TI - Characterization of autoinducer 2 signal in Eikenella corrodens and its role in
biofilm formation.
AB - Quorum sensing (QS) is a process by which bacteria communicate using secreted
chemical signaling molecules called autoinducers (AIs). By this process, many
bacterial species modulate the expression of a wide variety of physiological
functions in response to changes in population density. In this study, the
periodontal pathogen Eikenella corrodens was observed to secrete type 2 signaling
molecules. An ortholog of luxS, the gene required for AI-2 synthesis in Vibrio
harveyi, was isolated from the E. corrodens genome. A V. harveyi bioassay showed
luxS functionality in E. corrodens and the ability of luxS to complement the luxS
negative phenotype of Escherichia coli DH5alpha. AI activity was detected in the
supernatant, and the maximum expression of AI-2 was observed during the late
exponential phase. To determine the potential role of luxS in the colonization
processes, an E. corrodens luxS mutant was constructed and tested for its
capacity to form an in vitro biofilm on a polystyrene surface. The biofilm
forming efficiency of the luxS mutant was approximately 1.3-fold greater than
that of the wild type. These data suggest that a LuxS-dependent signal plays a
role in the biofilm formation by E. corrodens.
PMID- 17027873
TI - Transmission electron microscopic study on supramolecular nanostructures of
bacteriochlorophyll self-aggregates in chlorosomes of green photosynthetic
bacteria.
AB - Supramolecular nanostructures of bacteriochlorophyll (BChl) self-aggregates in
major light-harvesting complexes (chlorosomes) of green photosynthetic bacteria
were successfully observed by freeze-fracture transmission electron microscope.
Rod-shaped nanostructures with approximately 10 nm in diameter could be
visualized in three types of green sulfur bacteria (Chlorobium). Diameter of the
rod-shaped nanostructures in Chlorobium chlorosomes was independent of the
molecular structures of their light-harvesting pigments, namely BChl-c or d. In
contrast, chlorosomes of the green filamentous bacterium Chloroflexus aurantiacus
had rod-shaped nanostructures with approximately 5 nm in diameter. The present
results support that BChl self-aggregates in chlorosomes form rod-shaped
nanostructures called rod-elements with approximately 10- and 5-nm diameters for
Chlorobium and Chloroflexus, respectively.
PMID- 17027874
TI - Isolation and characterization of Streptomyces sp. NL15-2K capable of degrading
lignin-related aromatic compounds.
AB - Strain NL15-2K was isolated from soil by screening for bacteria capable of
catabolizing lignin-related aromatic acids. This isolate was identified as a
Streptomyces sp. on the basis of morphology and an analysis of its 16S rRNA gene
sequence. NL15-2K utilized caffeic acid, coniferyl alcohol, ferulic acid,
isovanillic acid, protocatechuic acid, vanillic acid, vanillin, and veratric acid
as sole carbon sources.
PMID- 17027876
TI - Thermotolerant Bacillus licheniformis TY7 produces optically active l-lactic acid
from kitchen refuse under open condition.
AB - A thermotolerant l-lactic-acid-producing bacterium was isolated and identified as
Bacillus licheniformis TY7. TY7 shows optimum growth at pH 6.5 at 30 degrees C
and normal growth up to 65 degrees C. Using nonsterile kitchen refuse at 50
degrees C, the strain produced 40 g/ll-lactic acid with 97% optical activity and
2.5 g/lxh productivity.
PMID- 17027875
TI - Selection of photosynthetic bacterium Rhodobacter sphaeroides 14F for
polyhydroxyalkanoate production with two-stage aerobic dark cultivation.
AB - Polyhydroxyalkanoate (PHA) production abilities in a two-stage aerobic dark
culture of photosynthetic bacteria were investigated at relatively high
temperatures (37-40 degrees C). A 14F strain, identified as Rhodobacter
sphaeroides, showed the highest PHA production (3.5 g/l PHA with 60% PHA
content). Its productivity was 2-3 times higher than those of other
photosynthetic bacteria.
PMID- 17027877
TI - Glucosylation of flavonols by Escherichia coli expressing glucosyltransferase
from rice (Oryza sativa).
AB - A glucosyltransferase cDNA, RF5, was cloned from Oryza sativa using an RT-PCR
strategy and expressed in Escherichia coli. Several flavonoids were tested for
their ability to serve as substrates for RF5. RF5 effectively glucosylated
kaempferol and quercetin to produce their 3-O-glucosides. Thus, RF5 could be
defined as a flavonol 3-O-glucosyltransferase. E. coli cells expressing RF5
effectively converted 100 microM of kaempferol and quercetin into their
corresponding glucosides.
PMID- 17027878
TI - Macrocyclic diarylheptanoids from Garuga pinnata.
AB - Three macrocyclic diarylheptanoids, 6'-hydroxygaruganin V (1), 9'
desmethylgarugamblin I (2) and 1,9'-didesmethylgaruganin III (3) were isolated
from the petroleum ether and dichloromethane extracts of the stem bark of Garuga
pinnata. The structures of these compounds were established by extensive
spectroscopic studies, including high field NMR and MS measurements.
PMID- 17027879
TI - Stereochenols A and B, two quinones from Stereospermum chelonoides.
AB - Two quinones, stereochenols A (1) and B (2) were isolated from a methanol extract
of the stem bark of Stereospermum chelonoides, in addition to the known
naphthoquinones, sterekunthal B (3) and sterequinone C (4). The structures of
these compounds were established by extensive spectroscopic analyses and by
comparison of their spectral data with those of related compounds.
PMID- 17027880
TI - Factors influencing the care needs and demands of rural outpatients in Shaanxi,
China.
PMID- 17027881
TI - Influenza vaccination coverage rates in the UK: a comparison of two monitoring
methods during the 2002-2003 and 2003-2004 seasons.
AB - OBJECTIVES: To assess the feasibility of measuring influenza vaccination coverage
during 2002-2003 and 2003-2004 seasons using a telephone survey; to compare these
findings with routine vaccine uptake monitoring based on data provided by general
practitioners. STUDY DESIGN: Telephone-based survey. METHODS: We interviewed a
random sample of non-institutionalized individuals representative of the
population aged 16 years and over. Four target groups were determined for
analysis: (1) people aged 65 years and over; (2) healthcare workers; (3) people
under 65 years with chronic illnesses, which placed them at risk for influenza;
and (4) a group composed of all three previous groups combined. RESULTS: The
overall sample consisted of 4054 people (about 2000 per season). Population
influenza vaccine coverage in the UK increased from 22.3% in 2002-2003 to 24.2%
in 2003-2004. Vaccine uptake was strongly age dependent, even in people aged 65
years and over (the ages at which all people are routinely targeted). In both
seasons, the estimates of vaccine uptake in people aged 65 years and over were
remarkably consistent with those obtained through routine monitoring. Vaccine
uptake in healthcare workers was markedly suboptimal. CONCLUSIONS: In the UK, a
telephone-based system of monitoring influenza vaccine uptake seems robust enough
to generate data that are comparable with routine vaccine monitoring undertaken
using data provided by general practitioners. Although such a system cannot
easily contribute towards monitoring of vaccination at local and regional levels,
it offers a validated method of estimating vaccine uptake that is independent of
healthcare workers' time. This may be especially important for a pandemic
vaccination programme, especially in countries in which healthcare resources are
scarce, or where the configuration of healthcare services is less conducive to
internal monitoring than is the case in the UK.
PMID- 17027882
TI - Preconditioning with low concentration NO attenuates subsequent NO-induced
apoptosis in vascular smooth muscle cells via HO-1-dependent mitochondrial death
pathway.
AB - Nitric oxide (NO) signaling pathways are important in both the maintenance of
vascular homeostasis and disease progression. Overproduction of NO has been
associated with ischemia/reperfusion (I/R) injury. Growing evidences suggest that
NO preconditioning has cytoprotective effects against I/R injury. However, the
mechanism with which NO mediates these effects remains to be elucidated. The
purpose of this study was to examine the mechanism of how NO preconditioning
inhibits subsequent NO-induced apoptosis in vascular smooth muscle cells (VSMC),
specifically focusing on heme oxygenase-1 (HO-1). According to our data, sodium
nitroprusside (SNP) increased HO-1 expression in a concentration dependent
manner. Preconditioning with low concentration SNP (0.3mM) inhibited subsequent
high concentration SNP (1.5mM)-induced apoptosis, and this effect was reversed by
the HO-1 inhibitor SnPP. Low concentration SNP-mediated protection involved p38
kinase inactivation and increased Bcl-2 expression. Furthermore, mitochondrial
membrane potential was concomitantly increased with decreased expressions of Bax,
Apaf-1, and activity of caspase-3, which was reversed by SnPP treatment. Our
results show that low concentration SNP preconditioning suppresses subsequent
high concentration SNP-induced apoptosis by inhibiting p38 kinase and
mitochondrial death pathway via HO-1-dependent mechanisms in VSMC.
PMID- 17027884
TI - Perspectives in multiple sclerosis health care: special focus on the costs of
multiple sclerosis.
AB - Brain disorders are amongst the leading causes of disease and disability
worldwide, accounting for 35% of the burden of all diseases in Europe. Despite
their enormous personal and national impact the knowledge of the financial and
economic impression of brain disorders has been relatively little researched.
Recently it has been estimated that there are nearly 400,000 multiple sclerosis
(MS) patients in Europe, which is 0.003% of all brain disease patients in the
continent. In MS economic consequences are predominantly the early loss of work
capacity and the impact of physical and psychological disabilities in a
population of young adults, hospitalization during severe disease exacerbations
and the need for assistance in activities of daily living. In the last decade the
introduction of new immunomodulatory treatments led to an increase in direct
costs due to the cost of these drugs, but also led to a more intensive management
of patients. However, most studies of MS costs were carried out prior to the
widespread use of newer treatments. In the present study we estimated the
economic impact of MS in Israel and compared the traditional-vertical management
model with the integrated-multidisciplinary model of health service delivery
following the introduction of immunomodulatory treatments. Mean direct health
cost was 8,554 euros and 5,599 euros in the traditional and integrative models,
respectively (p<0.01). After 1-year follow-up, full-time employment decreased by
10% in the traditional model and increased by 17% in the integrated model
(p<0.05). Analysis of variance demonstrated that the model of service delivery
explained most of the difference in cost between the two models. Compared to mean
annual costs in Europe that are estimated at 23,695 euros per case the cost of
health services in Israel by MS patients is significantly lower. MS represents a
high economic burden to society. In line with the findings from 15 studies
published in Europe, we can conclude that studies agree with the following
findings: a) costs outside the healthcare system, non-medical costs and informal
care dominate the costs of MS, b) costs increase with increasing severity of the
disease and c) an integrated service delivery model that is satisfying to
patients on the one hand and cost effective on the other is to be recommended.
PMID- 17027885
TI - Peripheral blood gene expression signature mirrors central nervous system
disease: the model of multiple sclerosis.
AB - Global gene expression analysis using cDNA microarrays has proven to be a
sensitive method to gain insight into molecular pathways mediating multiple
sclerosis (MS) activity and to develop and refine the molecular taxonomy of the
disease. This method was applied as a tool to investigate molecular heterogeneity
of MS related gene transcripts in the aim of distinguishing between transcripts
that trigger disease activity and account for direct genotype-phenotype
correlation, and those whose expression is altered as a downstream effect of
other genes. This review summarizes the current state of gene expression
microarray applications for the study of MS, and specifically emphasizes the
results of gene expression studies using peripheral blood mononuclear cells
(PBMC) that were shown to be useful for better understanding of disease related
pathways, monitoring of therapeutic responses to various drugs and prediction of
clinical outcome. In the long run it is expected that the information provided by
cDNA microarrays experiments will allow the determination of key molecular
players involved in MS pathogenesis, and lead to better management of the disease
using targeted treatments that will prevent its progression.
PMID- 17027886
TI - The immune system and happiness.
AB - Human ability to experience negative and positive emotions has an evolutionary
perspective and the presence of feelings designed to influence behavior should
thus be reflected in physiological and immune interactions. The complex
interactions between the immune system and the central nervous system have been
studied extensively in schizophrenia and depression. On the other hand, effects
of positive human emotions, especially happiness, on physiological parameters and
immunity have received very little attention. Emotions are intimately involved in
the initiation or progression of cancer, HIV, cardiovascular disease, and
autoimmune disorders. The specific physiological responses induced by pleasant
stimuli were recently investigated with the immune and endocrine systems being
monitored when pleasant stimuli such as odors and emotional pictures were
presented to subjects. The results revealed that an increase in secretory
immunoglobulin A and a decrease in salivary cortisol were induced by pleasant
emotions. The mechanisms by which positive as opposed to negative states are
instantiated in the brain and interact with the immune system are not yet
understood. The present review investigates relations among physiological
measures of affective style, psychological well-being, and immune function. There
is data to support the hypothesis that individuals characterized by a more
negative affective style poorly recruit their immune response and may be at risk
for illness more so than those with a positive affective style. Future research
is needed to expand our knowledge of the physiological and immune interactions of
positive emotional states and their beneficial effects on health.
PMID- 17027887
TI - Thrombin in inflammatory brain diseases.
AB - Inflammatory brain diseases such as multiple sclerosis (MS) include
hyperactivation of the coagulation pathway which includes thrombin. In the
experimental autoimmune encephalomyelitis (EAE) model we have found significantly
higher levels of thrombin inhibitors which include the very early elevation of
protease nexin 1. The physiological importance of excess thrombin in neural
tissue is demonstrated by recent experiments which link thrombin with conduction
block in the sciatic nerve.
PMID- 17027888
TI - A model for the comprehensive investigation of a chronic autoimmune disease: the
multiple sclerosis CLIMB study.
AB - Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous
system (CNS) resulting in various disabilities including weakness and imbalance,
visual abnormalities, changes in cognition, as well as bladder and sexual
dysfunction. The majority of patients begin with a relapsing-remitting course of
the disease until eventually there is a progressive decline in disability. With
FDA-approved disease modifying therapy now given to the majority of MS patients
early in the course of the disease, the advent of MRI imaging, as well as
advances in immunology and genetics, the study of MS has entered into an exciting
era. Natural history studies of untreated patients have provided a guide for
disease prognosis based on the clinical features of the disease but have limited
utility in this new era of MS. Major questions are unanswered, including how does
treatment affect the long-term clinical course of the disease and are there major
subcategories of the disease with different implications for treatment and
outcome. Advances in our ability to clinically measure and monitor the disease
through MRI imaging technology, immunology, and genetic analysis provide the
opportunity to address these critical questions.
PMID- 17027889
TI - Neuromyelitis optica - Devic's syndrome, update.
AB - Neuromyelitis optica of Devic (NMO) is a syndrome which combines transverse
myelitis and optic neuritis. For many years it was assumed that transverse
myelitis and optic neuritis should be simultaneous, that optic neuritis should be
bilateral, and that transverse myelitis must be complete. NMO was considered to
be very rare. Through the 20th century there was a debate on whether NMO is a
distinct nosologic entity or a form of MS. In 2005 it is now possible to
distinguish NMO from MS on the basis of the clinical, imaging, serology and
immunopathology profile. This distinction is necessary for the implementation of
adequate treatments, as the relapsing form of the illness carries significant
morbidity and mortality.
PMID- 17027890
TI - Novel image processing techniques to better understand white matter disruption in
multiple sclerosis.
AB - In Multiple Sclerosis (MS) patients, conventional magnetic resonance imaging
(MRI) shows a pattern of white matter (WM) disruption but may also overlook some
WM damage. Diffusion tensor MRI (DT-MRI) can provide important in-vivo
information about fiber direction that is not provided by conventional MRI. The
geometry of diffusion tensors can quantitatively characterize the local structure
in tissues. The integration of both conventional MRI and DT-MRI measures together
with connectivity-based regional assessment provide a better understanding of the
nature and the location of WM abnormalities. Image processing and visualization
techniques have been developed and applied to study conventional MRI and DT-MRI
of MS patients. These include methods of: Image Segmentation for identifying the
different areas of the brain as well as to discriminate normal from abnormal WM,
Computerized Atlases, which include structural information obtained from a set of
subjects, and Tractographies which can aid in the delineation of WM fiber tracts
by tracking connected diffusion tensors. These new techniques hold out the
promise of improving our understanding of WM architecture and its disruption in
diseases such as MS. In the present study, we review the work that has been done
in the development of these techniques and illustrate their applications.
PMID- 17027891
TI - European Working Party on Systemic Lupus Erythematosus: a 15-year report.
AB - The "European Working Party on Systemic Lupus Erythematosus" was created 15 years
ago in order to promote research in Europe on the different problems related to
this disease. Nowadays, more than 50 European centres are collaborating in this
venture, 9 large multicentre studies are ongoing and 10 workshops have been
organized.
PMID- 17027892
TI - Type-I interferons and systemic lupus erythematosus.
AB - Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease
characterized by the production of autoantibodies directed against nuclear
antigens and chronic inflammation affecting multiple tissues. Complex genetic
disorders are at the origin of the disease in humans and in SLE-prone mice,
leading to the escape of auto-reactive B-lymphocytes from central and peripheral
control checkpoints that operate normally in healthy organisms. Although
necessary, autoimmune B-cells are not sufficient and additional mechanisms such
as T-cell help are clearly needed for the disease to occur. The role of type-I
interferons (type-I IFNs), and in particular IFNalpha, as prominent cofactors for
SLE was suggested years ago. Leading observations in patients and recent data in
SLE-prone mice have now established IFNalpha as a major actor in SLE. Several
systemic clinical symptoms and laboratory findings can indeed be interpreted as
downstream effects of a high IFNalpha production, and point to this cytokine as a
link between the expansion of autoimmune B-cells and the stimulation of other
components of the immune system. Consequently, a vicious circle is established
with overt immune-cell activation and inflammatory infiltrates culminating in the
selective destruction of tissue targets, notably the kidney. These notions can
now be transplanted to the clinic and designate IFNalpha as a new promising
therapeutic target.
PMID- 17027893
TI - Transforming growth factor-beta signaling through the Smad proteins: role in
systemic sclerosis.
AB - Transforming growth factor-beta (TGF-beta) plays a critical role in the
development of tissue fibrosis. Its expression is consistently elevated in
affected organs and correlates with increased extracellular matrix deposition.
During the last few years, tremendous progress has been made in understanding the
molecular aspects of intracellular signaling downstream of the TGF-beta
receptors. In particular, Smad proteins, TGF-beta receptor kinase substrates that
translocate into the cell nucleus to act as transcription factors, have been
studied extensively. Their role in the transcriptional regulation of type I
collagen and other extracellular matrix (ECM) genes expression, and in the
development of fibrosis is of critical importance because it may lead to novel
therapeutic strategies for the treatment of these multi-organ tissue reactions to
injury. Systemic sclerosis (SSc) is a complex autoimmune disease characterized by
pathological remodelling of connective tissues correlated to the activation of
TGF-beta/Smad signaling pathway. This review focuses on the mechanisms underlying
Smad modulation of gene expression and how they relate to fibrotic process.
Potential implications for the development of therapeutic approaches against
tissue fibrosis during SSc are discussed.
PMID- 17027894
TI - Paramyxovirus Sendai virus V protein counteracts innate virus clearance through
IRF-3 activation, but not via interferon, in mice.
AB - The present study was undertaken to clarify the role of Sendai virus (SeV) V
protein, which has been shown to downregulate IFN-beta induction through
inhibition of IRF-3 activation, in viral pathogenesis. Mice infected with rSeV
mutants, deficient in V expression or expressing V lacking the C-terminus, had
several-fold higher IFN activity levels in the lungs than those in wild-type
virus-infected mice, and the mutant viruses were rapidly excluded from the lung
from the early phase of infection before induction of acquired immunity. In
addition, the unique early clearance of the mutants did not occur in IRF-3
knockout (KO) mice. However, high titers of IFN were detected even in the
infected KO mice. Furthermore, early clearance of the mutant viruses was also
observed in IFN signaling-deficient mice, IFN-alpha/beta receptor KO mice and
STAT1 KO mice. These results indicate that SeV V protein counteracts IRF-3
mediated innate antiviral immunity for efficient virus replication and
pathogenesis in mice, but it is not IFN.
PMID- 17027895
TI - Virion tails of Beet yellows virus: Coordinated assembly by three structural
proteins.
AB - Filamentous virions of Beet yellows virus contain a long body formed by a major
capsid protein and a short tail that is assembled by a minor capsid protein
(CPm), an Hsp70-homolog (Hsp70h), a 64-kDa protein (p64), and a 20-kDa protein
(p20). Using mutation analysis and newly developed in planta assays, here we
investigate the genetic requirements for the tail assembly. We show that the
inactivation of CPm dramatically reduces incorporation of both Hsp70h and p64.
Furthermore, inactivation of Hsp70h prevents incorporation of p64 into virions
and vice versa. Hsp70h and p64 are each required for efficient incorporation of
CPm. We also show that the tails possessing normal relative amounts of CPm,
Hsp70h, and p64 can be formed in the absence of the major capsid protein and p20.
Similar to the tails isolated from the wild-type virions, these mutant tails
encapsidate the approximately 700 nt-long, 5'-terminal segments of the viral RNA.
Taken together, our results imply that CPm, Hsp70h and p64 act cooperatively to
encapsidate a defined region of the closterovirus genome.
PMID- 17027896
TI - Anisotropic local contrast normalization: the role of stimulus orientation and
spatial frequency bandwidths in the oblique and horizontal effect perceptual
anisotropies.
AB - Visual ability for sine waves and other narrowband stimuli shows an oblique
effect--worst performance at obliques, best at horizontal and vertical
orientations. Recently, we have shown that with broadband stimuli (either
1/f(alpha) visual noise or natural scenes), performance for detecting oriented
content is worst at horizontal, best at the obliques, and intermediate at
vertical orientations (a "horizontal effect"). This horizontal effect has been
explained by a cortical contrast normalization model that is both local (over
orientation and spatial frequency) and anisotropic (due to a numerical bias of
neurons with different preferred orientations). Here, the bandwidth of content at
which an oblique effect or horizontal effect occurs was assessed in two
suprathreshold matching experiments conducted with 1/f(alpha) noise stimuli
filtered with a triangle increment function of varied bandwidth (16 levels of
orientation and spatial frequency bandwidth). The results provided further
support for the local anisotropic normalization model in that an oblique effect
was observed when a fairly small range of orientations and high spatial
frequencies were tested and the horizontal effect was observed for broadband
increments > or = 20 degrees orientation bandwidth and > or = 1-octave in
frequency. At intermediate spatial frequency and orientation increment
bandwidths, a blend of the two anisotropies was observed.
PMID- 17027897
TI - Centrins, gatekeepers for the light-dependent translocation of transducin through
the photoreceptor cell connecting cilium.
AB - Centrins are members of a highly conserved subgroup of the EF-hand superfamily of
Ca(2+)-binding proteins commonly associated with centrosome-related structures.
In the retina, centrins are also prominent components of the photoreceptor cell
ciliary apparatus. Centrin isoforms are differentially localized at the basal
body and in the lumen of the connecting cilium. All molecular exchanges between
the inner and outer segments occur through this narrow connecting cilium. Ca(2+)
activated centrin isoforms bind to the visual heterotrimeric G-protein transducin
via an interaction with the betagamma-subunit. Ca(2+)-dependent assemblies of
centrin/G-protein complexes may regulate the transducin movement through the
connecting cilium. Formation of this complex represents a novel mechanism in
regulation of translocation of signaling proteins in sensory cells, as well as a
potential link between molecular trafficking and signal transduction in general.
PMID- 17027898
TI - Insights into functional aspects of centrins from the structure of N-terminally
extended mouse centrin 1.
AB - Centrins are members of the family of Ca(2+)-binding EF-hand proteins. In
photoreceptor cells, centrin isoform 1 is specifically localized in the non
motile cilium. This connecting cilium links the light-sensitive outer segment
with the biosynthetic active inner segment of the photoreceptor cell. All
intracellular exchanges between these compartments have to occur through this
cilium. Three-dimensional structures of centrins from diverse organisms are
known, showing that the EF-hand motifs of the N-terminal domains adopt closed
conformations, while the C-terminal EF-hand motifs have open conformations. The
crystal structure of an N-terminally extended mouse centrin 1 (MmCen1-L)
resembles the overall structure of troponin C in its two Ca(2+) bound form.
Within the N-terminal extension in MmCen1-L, residues W24 and R25 bind to the C
terminal domain of centrin 1 in a target-protein-like geometry. Here, we discuss
this binding mode in connection with putative interaction sites of the target
protein transducin and the self-assembly of centrins.
PMID- 17027899
TI - A methyl group at C7 of 11-cis-retinal allows chromophore formation but affects
rhodopsin activation.
AB - The newly synthesized 11-cis-7-methylretinal can form an artificial visual
pigment with kinetic and spectroscopic properties similar to the native pigment
in the dark-state. However, its photobleaching behavior is altered, showing a
Meta I-like photoproduct. This behavior reflects a steric constraint imposed by
the 7-methyl group that affects the conformational change in the binding pocket
as a result of retinal photoisomerization. Transducin activation is reduced, when
compared to the native pigment with 11-cis-retinal. Molecular dynamics
simulations suggest coupling of the C7 methyl group and the beta-ionone ring with
Met207 in transmembrane helix 5 in agreement with recent experimental results.
PMID- 17027900
TI - Enantioselective separation and determination of single nonylphenol isomers.
AB - It has recently become clear that an isomer specific view of technical 4
nonylphenol (NP) is absolutely necessary for the evaluation of the biological
behavior of NP, raising additional questions concerning enantiomer specific
effects. For the first time, in this study enantioselective HPLC was applied to
enantiomeric separation of chiral NP isomers. A semipreparative separation of two
NP isomers could be achieved. A GC-MS method has been developed for the
simultaneous detection of three chiral NP isomers in water samples. Investigation
of influent and effluent samples from a wastewater treatment plant in Germany
indicated that enantioselective degradation could occur in the environment. In
one examined influent, an enantiomer ratio of 1.7 for two different isomers was
determined.
PMID- 17027901
TI - High-resolution characterization of antibody fragment/antigen interactions using
Biacore T100.
AB - A Biacore T100 optical biosensor was used to characterize the binding kinetics of
a panel of antigen binding fragments (Fabs) directed against the PcrV protein
from Pseudomonas aeruginosa. PcrV protein forms part of the type III secretion
system complex of this opportunistic pathogen. We demonstrate that the biosensor
response data for each Fab collected from three different surface densities of
the antigen could be fit globally to a simple 1:1 interaction model. Importantly,
we found that the Fabs with the slowest dissociation rate provided the best
protection in cell cytotoxicity studies. To further characterize the Fab
interactions, binding data were automatically acquired at different temperatures
and under different buffer conditions. The comprehensive characterization of
these Fabs shows how Biacore T100 can be used to complement protein therapeutic
discovery programs from basic research to the selection of therapeutic
candidates.
PMID- 17027902
TI - Quantification of defensins by matrix-assisted laser desorption/ionization time
of-flight mass spectrometry.
PMID- 17027903
TI - Comparative quantification of sphingolipids and analogs in biological samples by
high-performance liquid chromatography after chloroform extraction.
AB - Sphingosine 1-phosphate (S1P) is an extra- and intracellular messenger that
specifically activates five G-protein-coupled cell surface receptors designated
S1P(1-5). The S1P(1) receptor is particularly important for the maintenance of
immune surveillance by regulating egress of lymphocytes from thymus and secondary
lymphoid organs. S1P is generated through phosphorylation of sphingosine which is
catalyzed by sphingosine kinase types 1 and 2. The immunosuppressant and
sphingosine analog Fingolimod (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3
propanediol, FTY720) can also be phosphorylated and induces lymphopenia by
downregulating cell surface expression of the S1P(1) receptor on lymphocytes. To
analyze the role of S1P in lymphocyte circulation and distribution we established
a high-performance-liquid-chromatography-based method for parallel detection and
quantification of Fingolimod, sphingosine, and dihydrosphingosine together with
their phosphorylated derivatives Fingolimod-phosphate, S1P, and
dihydrosphingosine 1-phosphate. Phosphorylated and nonphosphorylated lipids were
efficiently isolated from biological samples such as cells, tissues, serum,
plasma, and media by simple chloroform extraction. Fluorescence labeling with 9
fluorenylmethyl chloroformiate ensured high selectivity and enhanced sensitivity
for sphingolipid detection. The described method provides an accurate approach to
investigate phosphorylation, dephosphorylation, hydrolyzation, and
dehydrolyzation of sphingolipids and analogs. In addition it works independently
from enzymatic conversions, measuring actual concentrations rather than enzymatic
activities.
PMID- 17027904
TI - Proton nuclear magnetic resonance spectroscopic determination of ethanol-induced
formation of ethyl glucuronide in liver.
AB - Ethyl glucuronide (ethyl-beta-D-6-glucosiduronic acid, EtG), a unique metabolite
of ethanol, has received much recent attention as a sensitive and specific
biological marker of ethanol consumption. Formed in the liver via conjugation of
ethanol with activated glucuronate, EtG remains detectable in serum, plasma, and
hair for days after ethanol abuse. Thus far, gas chromatography-mass spectrometry
and enzyme-linked immunosorbent assays have been developed to detect trace
quantities of EtG for forensic purposes, but reports of the nuclear magnetic
resonance (NMR) properties of EtG have been scarce. Herein we present the first
report of EtG determination using proton NMR spectroscopy. We collected 700-MHz
proton spectra of liver extracts from rats treated with a 4-day binge ethanol
protocol (average ethanol dose: 8.6g/kg/day). An unexpected signal (triplet, 1.24
ppm) appeared in ethanol-treated liver extracts but not in control samples; based
on chemical shift and multiplicity, we suspected EtG. We observed quantitative
hydrolysis of the unknown species to ethanol while incubating our samples with
beta-glucuronidase, confirming that the methyl protons of EtG were responsible
for the triplet at 1.24 ppm. This study demonstrates that proton NMR spectroscopy
is capable of detecting EtG and that future NMR-based metabolomic studies may
encounter this metabolite of ethanol.
PMID- 17027905
TI - A homemade cytospin apparatus.
PMID- 17027906
TI - Development of a viologen-based microtiter plate assay for the analysis of
oxyanion reductase activity: application to the membrane-bound selenate reductase
from Enterobacter cloacae SLD1a-1.
AB - The membrane-bound selenate reductase of Enterobacter cloacae SLD1a-1 is purified
in low yield and has relatively low activity in the pure form compared to that of
other oxyanion reductases, such as the membrane-bound and periplasmic nitrate
reductases. A microtiter plate assay based on the original quartz cuvette
viologen assay of Jones and Garland (R.W. Jones, P.B. Garland, Biochem. J 164
(1977) 199-211) was developed specifically for analysis of such low-abundant,
labile oxyanion reductases. The plate assay detects the enzyme-dependent
reoxidation of reduced methyl viologen spectrophotometrically at 600 nm. The
assay is quick, uses a minimal sample volume (<5 microl), can simultaneously test
a range of alternative substrates, and permits activity measurements on multiple
samples. We demonstrate the accuracy and versatility of the microtiter plate
assay by application to the kinetic analysis, inhibition, and pH optimization of
the membrane-bound selenate reductase from E. cloacae SLD1a-1. Results show that
the membrane-bound selenate reductase has optimum activity at pH approximately 8
and its active site is able to accommodate larger inhibitory complexes resulting
in mixed-type inhibition, in the presence of selenate and potassium thiocyanate.
PMID- 17027908
TI - 23-carboxy-24,25,26,27-tetranorvitamin D3 (calcioic acid) and 24-carboxy-25,26,27
trinorvitamin D3 (cholacalcioic acid): end products of 25-hydroxyvitamin D3
metabolism in rat kidney through C-24 oxidation pathway.
AB - During the past two and half decades the elucidation of the metabolic pathways of
25OHD(3) and its active metabolite 1alpha,25(OH)(2)D(3) progressed in parallel.
In spite of many advances in this area of vitamin D research, the unequivocal
identification of the end products of 25OHD(3) metabolism through C-24 oxidation
pathway has not been achieved. It is now well established that both 25OHD(3) and
1alpha,25(OH)(2)D(3) are metabolized through the same C-24 oxidation pathway
initiated by the enzyme 24-hydroxylase (CYP24A1). Based on the information that
the end product of 1alpha,25(OH)(2)D(3) metabolism through C-24 oxidation pathway
is 1alpha-OH-23- COOH-24,25,26,27-tetranor D(3) or calcitroic acid; the
metabolism of 25OHD(3) into 23-COOH-24,25,26,27-tetranor D(3) has been assumed.
Furthermore, a previous study indicated 24-COOH-25,26,27-trinor D(3) as a water
soluble metabolite of 24R,25(OH)(2)D(3) produced in rat kidney homogenates.
Therefore, 24-COOH-25,26,27-trinor D(3) was also assumed as another end product
of 25OHD(3) metabolism through C-24 oxidation pathway. We embarked on our present
study to provide unequivocal proof for these assumptions. We first studied the
metabolism of 25OHD(3) at low substrate concentration (3x10(-10)M) using [1,2
(3)H]25OHD(3) as the substrate in the perfused rat kidneys isolated from both
normal and vitamin D(3) intoxicated rats. A highly polar water soluble
metabolite, labeled as metabolite X was isolated from the kidney perfusate. The
amount of metabolite X produced in the kidney of a vitamin D intoxicated rat was
about seven times higher than that produced in the kidney of a normal rat. We
then produced metabolite X in a quantity sufficient for its structure
identification by perfusing kidneys isolated from vitamin D intoxicated rats with
high substrate concentration of 25OHD(3) (5x10(-6)M). Using the techniques of
electron impact and thermospray mass spectrometry, we established that the
metabolite X contained both 23-COOH-24,25,26,27-tetranor D(3) and 24-COOH
25,26,27-trinor D(3) in a ratio of 4:1. The same metabolite X containing both
acids in the same ratio of 4:1 was also produced when 24R,25(OH)(2)D(3) was used
as the starting substrate. Previously, the trivial name of cholacalcioic acid was
assigned to 24-COOH-25,26,27-trinorvitamin D(3). Using the same guidelines, we
now assign the trivial name of calcioic acid to 23-COOH-24,25,26,27-tetranor
D(3). In summary, for the first time our study provides unequivocal evidence to
indicate that both calcioic and cholacalcioic acids as the end products of
25OHD(3) metabolism in rat kidney through C-24 oxidation pathway.
PMID- 17027907
TI - Serum heat shock protein 70 level as a biomarker of exceptional longevity.
AB - Heat shock proteins are highly conserved proteins that, when produced
intracellularly, protect stress exposed cells. In contrast, extracellular heat
shock protein 70 (Hsp70) has been shown to have both protective and deleterious
effects. In this study, we assessed heat shock protein 70 for its potential role
in human longevity. Because of the importance of HSP to disease processes,
cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in
centenarians and centenarian offspring are different from controls and (2)
alleles in genes associated with Hsp70 explain these differences. In this cross
sectional study, we assessed serum Hsp70 levels from participants enrolled in
either the New England Centenarian Study (NECS) or the Longevity Genes Project
(LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126
controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic
frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266
from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls
(NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79
spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS
centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls
were 1.05, 1.13, 3.07, 6.93, respectively, suggesting that a low serum Hsp70
level is associated with longevity; however, no genetic associations were found
with two SNPs within two hsp70 genes.
PMID- 17027909
TI - Investigation of the role of cytochrome P450 2B4 active site residues in
substrate metabolism based on crystal structures of the ligand-bound enzyme.
AB - Based on the X-ray crystal structures of 4-(4-chlorophenyl)imidazole (4-CPI)- and
bifonazole (BIF)-bound P450 2B4, eight active site mutants at six positions were
created in an N-terminal modified construct termed 2B4dH and characterized for
enzyme inhibition and catalysis. I363A showed a >4-fold decrease in differential
inhibition by BIF and 4-CPI (IC(50,BIF)/IC(50,4-CPI)). F296A, T302A, I363A,
V367A, and V477A showed a 2-fold decreased k(cat) for 7-ethoxy-4
trifluoromethylcoumarin O-deethylation, whereas V367A and V477F showed an altered
K(m). T302A, V367L, and V477A showed >4-fold decrease in total testosterone
hydroxylation, whereas I363A, V367A, and V477F showed altered stereo- and
regioselectivity. Interestingly, I363A showed a 150-fold enhanced k(cat)/K(m)
with testosterone, and yielded a new metabolite. Furthermore, testosterone
docking into three-dimensional models of selected mutants based on the 4-CPI
bound structure suggested a re-positioning of residues 363 and 477 to yield
products. In conclusion, our results suggest that the 4-CPI-bound 2B4dH/H226Y
crystal structure is an appropriate model for predicting enzyme catalysis.
PMID- 17027910
TI - Biological and functional responses of in situ bioassays with Chironomus riparius
larvae to assess river water quality and contamination.
AB - Single species responses have the potential to measure impacts at earlier stages
than more traditional methods based in community structure. This study evaluates
a bioassay with biological (survival, development, growth) and functional (post
exposure feeding rate) responses of Chironomus riparius larvae to assess water
quality and contamination in rivers. The bioassay with C. riparius third instar
larvae was performed, in autumn and spring, in reference sites and in organic and
metal contaminated sites in Portuguese rivers. Biotic, physical and chemical
parameters were determined for each site. The relationship between both bioassays
responses and biotic indices (IBMWP and IASPT) and the physical and chemical
parameters of respective sites were determined. In general biotic indices were
able to discriminate between contaminated and not contaminated sites although
they demonstrated a poor ability to detect low level of metal contamination
during autumn. IASPT was negatively related to ammonia concentrations in both
seasons. No significant differences in survival and post-exposure feeding rate
were found between sites. Development was inhibited in the most metal
contaminated site during autumn, but pH and ammonia concentrations in water
accounted for 82% of developmental variation during this season. Growth was
highly inhibited in the most metal contaminated site during both seasons. In
autumn, growth was also inhibited in the low metal contaminated site and, during
this season, pH and Mn and Fe concentrations in water samples accounted for 97%
of growth variation between sites. The results suggest that in situ bioassay with
C. riparius larvae using growth as the endpoint is a responsive and suitable tool
that can be used as bioindicator of metal pollution and to biomonitor water
quality in metal contaminated rivers.
PMID- 17027911
TI - Stress reactivity and coping in seasonal and nonseasonal depression.
AB - Stress, stress reactivity, and coping skill use were examined in individuals with
seasonal depression, nonseasonal depression, and nondepressed controls. Although
participants in the two depressed groups reported using more avoidance coping
strategies than controls, only participants in the seasonal depressed group
reported using more season-specific coping (i.e., light-related strategies) than
participants in the nonseasonal depressed and control groups. Individuals in the
seasonal depressed group also reporting using acceptance coping strategies less
frequently than individuals in the control group. Only participants in the
nonseasonal depressed group, however, exhibited greater psychophysiological
arousal in reaction to a laboratory stressor (i.e., unsolvable anagram task) when
compared to participants in the seasonal and nondepressed control groups.
Participants in both depressed groups reported greater impact of negative life
events during the past 6 months than did controls. Similarities and differences
in the two types of depression may have implications for the conceptualization
and treatment of seasonal depression.
PMID- 17027912
TI - Zuotin, a DnaJ molecular chaperone, stimulates cap-independent translation in
yeast.
AB - A small inhibitor RNA (IRNA) isolated from yeast has previously been shown to
efficiently block poliovirus and hepatitis C virus IRES-mediated translation by
sequestering mammalian RNA-binding (transacting) factors that play important
roles in cap-independent translation. Here we have investigated the IRNA-binding
proteins that might be involved in cap-independent translation in the yeast
Saccharomyces cerevisiae. We have identified Zuotin, a DnaJ chaperone protein
similar to mammalian HSP-40 chaperone, which interacts strongly with IRNA. Using
ZUO1-deleted S. cerevisiae, we demonstrate a preferential requirement of Zuo1p
for cap-independent translation mediated by the 5' untranslated region of the
yeast TFIID mRNA. Further studies using zuo1delta S. cerevisiae complemented with
various Zuo1p mutants indicate that the DnaJ domain of Zuo1p, known to influence
its interaction with HSP-70, significantly affects cap-independent translation.
These results demonstrate for the first time a role for an established chaperone
protein in cap-independent translation of a cellular mRNA.
PMID- 17027913
TI - Hyaluronidase increases the biodistribution of acid alpha-1,4 glucosidase in the
muscle of Pompe disease mice: an approach to enhance the efficacy of enzyme
replacement therapy.
AB - Pompe disease (glycogen storage disease type II) is a glycogen storage disease
caused by a deficiency of the lysosomal enzyme, acid maltase/acid alpha-1,4
glucosidase (GAA). Deficiency of the enzyme leads primarily to intra-lysosomal
glycogen accumulation, primarily in cardiac and skeletal muscles, due to the
inability of converting glycogen into glucose. Enzyme replacement therapy (ERT)
has been applied to replace the deficient enzyme and to restore the lost
function. However, enhancing the enzyme activity to the muscle following ERT is
relatively insufficient. In order to enhance GAA activity into the muscle in
Pompe disease, efficacy of hyaluronidase (hyase) was examined in the heart,
quadriceps, diaphragm, kidney, and brain of mouse model of Pompe disease.
Administration of hyase 3000 U/mouse (intravenous) i.v. or i.p. (intraperitoneal)
and 10 min later recombinant human GAA (rhGAA) 20 mg/kg i.v. showed more GAA
activity in hyase i.p. injected mice compared to those mice injected with hyase
via i.v. Injection of low dose of hyase (3000 U/mouse) or high dose of hyase
(10,000 U/mouse) i.p. and 20 min or 60 min later 20 mg/kg rhGAA i.v. increased
GAA activity into the heart, diaphragm, kidney, and quadriceps compared to hyase
untreated mice. These studies suggest that hyase enhances penetration of enzyme
into the tissues including muscle during ERT and therefore hyase pretreatment may
be important in treating Pompe disease.
PMID- 17027914
TI - Identification of two isoforms of Dsk2-related protein XDRP1 in Xenopus eggs.
AB - The budding yeast UbL-UBA protein Dsk2 has a UbL domain at its N-terminus and a
UBA domain at its C-terminus, and thus functions as a shuttle protein in the
ubiquitin-proteasome pathway. In this report we describe two isoforms of Xenopus
Dsk2-related protein, XDRP1L and XDRP1S. Difference of the two proteins in
sequence was that the UbL domain of XDRP1S lacks 15 residues in the middle part
of that of XDRP1L. Both XDRP1L and XDRP1S were expressed in Xenopus eggs. XDRP1L
and XDRP1S bound to polyubiquitinated proteins via their UBA domains. XDRP1L also
bound to the proteasome via its UbL domain, whereas the XDRP1S UbL domain was
less likely to bind to the proteasome. Instead, XDRP1S not XDRP1L bound to
monomeric cyclin A and prevented its degradation. The existence of such Dsk2
isoforms in Xenopus eggs suggests that the shuttling function via the UbL-UBA
protein Dsk2 is evolutionally conserved across species.
PMID- 17027915
TI - Different expression patterns of TRP genes in murine B and T lymphocytes.
AB - A prolonged increase in the intracellular calcium concentration ([Ca2+]i) is
essential for lymphocyte activation that includes cell proliferation and
differentiation. This increase in [Ca2+]i results from Ca2+ release from the
intracellular store and the subsequent Ca2+ influx from the extracellular
environment via calcium channels located on the plasma membrane. Although
transient receptor potential (TRP) channels have been reported to play important
roles in the [Ca2+]i increase in lymphocytes, the function of these channels in
lymphocyte activation remains unknown. Here, we report the comprehensive
expression profile of TRP channel gene families including TRPC, TRPV, and TRPM in
the murine immune system. RT-PCR analysis revealed different expression patterns
of the TRP channel genes in B and T lymphocytes isolated from the spleen.
Therefore, our results provide an appropriate reference of TRP gene expression in
murine lymphocytes.
PMID- 17027916
TI - Isoproterenol suppresses cytokine-induced RANTES secretion in human lung
epithelial cells through the inhibition of c-jun N-terminal kinase pathway.
AB - It has been reported that beta2-agonists may potentially exert some anti
inflammatory action in addition to bronchodilation that may contribute to their
beneficial effects on asthma control. Bronchial epithelial cells are well known
to respond to a range of stimuli by producing various biologically active
mediators that can influence airway inflammation. RANTES (regulated on
activation, normal T cells expressed and secreted) plays an important role in the
pathophysiology of airway inflammation of asthmatics through its chemotactic
activity for eosinophils. In this study, the authors investigated whether
cytokine-induced RANTES release from BEAS-2B human bronchial epithelial cells
could be modulated by beta-agonist isoproterenol (ISO). The possible involvement
of c-jun N-terminal kinase (JNK) pathway was also studied. Combination of tumor
necrosis factor-alpha and interleukin-1beta (cytokine mix) increased RANTES
release from BEAS-2B cells and stimulated JNK activity. Similar to JNK inhibitor
SP600125, ISO inhibited not only the production of RANTES but also the activation
of JNK pathway in cytokine mix-stimulated BEAS-2B cells. The effect of ISO was
mediated by the beta2-adrenoceptor, since it was blocked by ICI 118,551, a
selective beta2-receptor antagonist, but not by atenolol, a selective beta1
receptor antagonist. Adenylyl cyclase activator forskolin reproduced the effects
of ISO. Isoproterenol was found to inhibit the release of RANTES from the human
bronchial epithelial cells, at least in part, through the inhibition of JNK
signaling pathway.
PMID- 17027917
TI - Necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and
TLR3: implication in Wallerian degeneration.
AB - Schwann cells play an important role in peripheral nerve regeneration. Upon nerve
injury, Schwann cells are activated and produce various proinflammatory cytokines
and chemokines, resulting in the recruitment of macrophages and the phagocytosis
of myelin debris. However, it is unclear how nerve injury induces Schwann cell
activation. Recently, it was reported that necrotic cells induce immune cell
activation via toll-like receptors (TLRs). This suggests that the TLRs expressed
on Schwann cells may recognize nerve injury by binding to the endogenous ligands
secreted by the damaged nerve, thereby inducing Schwann cell activation. To
explore such a possibility, we stimulated rat Schwann cells with necrotic
neuronal cells (NNC). The stimulation of Schwann cells with NNC induced the
expression of various inflammatory mediators, including TNF-alpha and iNOS.
Studies on the NNC-mediated intracellular signaling pathways revealed that p38
and JNK are involved in the NNC-mediated Schwann cell activation. In addition,
NNC-induced proinflammatory gene expression was reduced in mouse Schwann cells
derived from TLR2 or TLR3 knockout mice. In summary, these results suggest that
necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and
TLR3, which might be involved in Wallerian degeneration upon peripheral nerve
injury.
PMID- 17027918
TI - Trafficking defect of mutant kidney anion exchanger 1 (kAE1) proteins associated
with distal renal tubular acidosis and Southeast Asian ovalocytosis.
AB - Compound heterozygous anion exchanger 1 (AE1) SAO/G701D mutations result in
distal renal tubular acidosis with Southeast Asian ovalocytosis. Interaction,
trafficking and localization of wild-type and mutant (SAO and G701D) kAE1
proteins fused with hemagglutinin, six-histidine, Myc, or green fluorescence
protein (GFP) were examined in human embryonic kidney (HEK) 293 cells. When
individually expressed, wild-type kAE1 was localized at cell surface while mutant
kAE1 SAO and G701D were intracellularly retained. When co-expressed, wild-type
kAE1 could form heterodimer with kAE1 SAO or kAE1 G701D and could rescue mutant
kAE1 proteins to express on the cell surface. Co-expression of kAE1 SAO and kAE1
G701D also resulted in heterodimer formation but intracellular retention without
cell surface expression, suggesting their trafficking defect and failure to
rescue each other to the plasma membrane, most likely the molecular mechanism of
the disease in the compound heterozygous condition.
PMID- 17027919
TI - MRSP1, encoding a novel Trichoderma secreted protein, is negatively regulated by
MAPK.
AB - A novel gene, MRSP1 (MAP kinase repressed secreted protein 1) is strongly
overexpressed in the tmkA MAPK mutant of the biocontrol fungus Trichoderma
virens. Transcriptional regulation of MRSP1 is determined by presence or absence
of TmkA, rather than by light or sporulation, making it a molecular marker for
the unusual, negative, regulation by TmkA. The predicted protein is 15.9 kDa, has
a secretory signal, and the four-cysteine pattern, C-X29-CP(G)C-X31-C, may define
a new cysteine-rich motif. This is a novel protein with functions not known from
any other organism. Conservation in ascomycete, basidiomycete, and Dictyostelium
homologs, as well as tight MAPK regulation, might indicate important cellular
functions.
PMID- 17027920
TI - Lipid fluidity at different regions in LDL and HDL of beta-thalassemia/Hb E
patients.
AB - Atherosclerosis-related vascular complications in beta-thalassemia/hemoglobin E
(beta-thal/Hb E) patients may result from iron induced oxidation of lipoproteins.
To identify the specific site of oxidative damage, changes in lipid fluidity at
different regions in LDL and HDL particle were investigated using two
fluorescence probes and two ESR spin probes. The magnitude of increased lipid
fluidity in thalassemic lipoproteins was dependent on the location of the probes.
In hydrophobic region, the rotational correlation times for 16-doxyl stearic acid
and DPH anisotropy were markedly changed in LDL and HDL of the patients. In the
surface region, there was only a slight change in the order parameter (S) for 5
doxyl stearic acid and TMA-DPH anisotropy. Lipid fluidity at the core of LDL and
HDL showed good correlation with oxidative stress markers, the ratio of CL/CO,
and the level of alpha-tocopherol, suggesting that hydrophobic region of
thalassemic lipoprotein was a target site for oxidative damage.
PMID- 17027921
TI - Quantitative measurement of damage caused by 1064-nm wavelength optical trapping
of Escherichia coli cells using on-chip single cell cultivation system.
AB - We quantitatively examined the possible damage to the growth and cell division
ability of Escherichia coli caused by 1064-nm optical trapping. Using the
synchronous behavior of two sister E. coli cells, the growth and interdivision
times between those two cells, one of which was trapped by optical tweezers, the
other was not irradiated, were compared using an on-chip single cell cultivation
system. Cell growth stopped during the optical trapping period, even with the
smallest irradiated power on the trapped cells. Moreover, the damage to the
cell's growth and interdivision period was proportional to the total irradiated
energy (work) on the cell, i.e., irradiation time multiplied by irradiation
power. The division ability was more easily affected by a smaller energy, 0.36 J,
which was 30% smaller than the energy that adversely affected growth, 0.54 J. The
results indicate that the damage caused by optical trapping can be estimated from
the total energy applied to cells, and furthermore, that the use of optical
trapping for manipulating cells might cause damage to cell division and growth
mechanisms, even at wavelengths under 1064 nm, if the total irradiation energy is
excessive.
PMID- 17027922
TI - mBET3 is required for the organization of the TRAPP complexes.
AB - Large tethering complexes mediate the initial interaction of a transport vesicle
with its target membrane. There are two forms of the multi-subunit tethering
complex called TRAPP (TRAPPI and TRAPPII) that tether transport vesicles in
different trafficking steps. Understanding TRAPP complex assembly and the protein
protein interactions among the subunits is an important step in elucidating the
function of this tether. Here we have used several different approaches to study
the protein-protein interactions among the subunits of the TRAPP complexes in
both mammalian cells and yeast. Our studies have revealed that the low molecular
weight subunits of TRAPP form two subcomplexes in vitro. One subcomplex contains
mammalian BET3 (mBET3), mTRS31 and mTRS20, while mBET5 and mTRS23 form a second
subcomplex. Furthermore, mBET3 directly interacts with mBET5 in vitro. Our
findings also suggest that the TRAPPII-specific subunit, yTrs120p (yeast
Trs120p), binds to the periphery of the TRAPPII complex. Although the non
essential TRAPP subunit yTrs33p interacts with yBet3p, yTrs33p is not required
for TRAPP complex assembly. Together our findings indicate that BET3 plays an
important role in the organization of the TRAPP complexes in both mammalian cells
and yeast.
PMID- 17027923
TI - Identification and analysis of the mouse basic/Helix-Loop-Helix transcription
factor family.
AB - The basic/Helix-Loop-Helix (bHLH) proteins are a family of transcription factors
that regulates a variety of biological processes. Based on a previously defined
consensus motif, we identified the complete set of bHLH protein family from the
mouse proteome databases and carried out a series of bioinformatics analysis. As
results, 124 mouse bHLH proteins were identified in this study, and 28 of them
were additional bHLH proteins beyond the previous report. These 124 mouse bHLH
proteins were classified into groups from A to F by the nomenclature and
phylogenetic analysis. Statistic analysis of the Gene Ontology annotation of
these proteins showed that the bHLH proteins tend to perform functions related to
cell differentiation and development. Gene function enrichment analysis among six
groups illuminated that the proteins in certain group tend to have special
biology functions, so that the molecular function of the uncharacterized proteins
in groups could be inferred.
PMID- 17027924
TI - Fucoidan prevents C epsilon germline transcription and NFkappaB p52 translocation
for IgE production in B cells.
AB - Fucoidan, a dietary fiber contained in seaweed, reduces the increase of antigen
specific IgE in mice exposed to ovalbumin. In this study, we investigated the
effect of fucoidan on IgE production and intracellular events in B cells in
vitro. Fucoidan inhibited the production of IgE and C epsilon germline
transcription in murine B cells induced by IL-4 (100 ng/ml) and anti-CD40
antibodies (10 microg/ml), whereas it stimulated cell proliferation. A
significant effect of fucoidan on IgE production was observed when B cells were
stimulated with a higher dose (5 microg/ml) of anti-CD40 antibodies, but not when
stimulated with lower doses (1.25, 2.5 microg/ml), regardless of the IL-4
concentrations. Moreover, nuclear translocation of NFkappaB p52, but neither that
of NFkappaB p65, nor the phosphorylation of JAK1 and STAT6 was reduced by
fucoidan. These results suggest that fucoidan inhibited IgE production by
preventing the NFkappaB p52-mediated pathways activated by CD40.
PMID- 17027925
TI - A Cdc2-sensitive interaction of the UbL domain of XDRP1S with cyclin B mediates
the degradation of cyclin B in Xenopus egg extracts.
AB - The yeast UbL-UBA protein Dsk2 is thought to act as a shuttle protein that
delivers polyubiquitinated proteins to the proteasome. Previously, we identified
Xenopus Dsk2-related protein, XDRP1, as a cyclin A-interacting protein. Using
Xenopus egg extracts, we further characterized its two isoforms, XDRP1L and
XDRP1S, with respect to cyclin binding and its degradation. Polyubiquitinated
cyclins bound to the UBA domain of XDRP1L and XDRP1S, whereas monomeric cyclins A
and B bound to the UbL domain of XDRP1S but not to XDRP1L. Binding of XDRP1S with
monomeric cyclins was affected by a Cdc2-mediated phosphorylation of either the
XDRP1S UbL domain or cyclins. Degradation of cyclin B was also prevented by
XDRP1S in a Cdc2-sensitive manner. Loss of the XDRP1S-cyclin interaction allowed
cyclins to be degraded in calcium-treated CSF extracts. These results suggest
that the shuttling pathway via the UbL-UBA protein XDRP1 participates in
degradation of mitotic cyclins in Xenopus eggs.
PMID- 17027927
TI - Neural circuits containing pallidotegmental GABAergic neurons are involved in the
prepulse inhibition of the startle reflex in mice.
AB - BACKGROUND: Prepulse inhibition (PPI) of the startle response is a measure of the
inhibitory function and time-linked information processing by which a weak
sensory stimulus (the prepulse) inhibits the startle response caused by a sudden
intense stimulus. We attempted to clarify the neuronal circuits underlying the
control of PPI of the startle reflex in mice. METHODS: c-Fos immunohistochemistry
was used to detect neurons activated by startle pulse and/or prepulse trials.
Behavioural pharmacology and tracing studies were also conducted. RESULTS: The
lateral globus pallidus (LGP) was activated by prepulses. Activation of the
caudal pontine reticular nucleus (PnC) evoked by the startle pulses was inhibited
under PPI conditions. Double-immunostaining revealed that c-Fos-positive cells in
the LGP following prepulse trials were GABAergic neurons. Bilateral
microinjections of lidocaine into the LGP resulted in an impairment of PPI.
Fluoro-gold infusion into the PnC and the pedunculopontine tegmental nucleus
(PPTg) retrogradely labeled neurons in the PPTg and LGP, respectively.
Microinjections of phaclofen into the PPTg significantly impaired PPI.
CONCLUSIONS: These results suggest that GABAergic neurons in the LGP which
project to the PPTg play a crucial role through the activation of GABAB receptors
in the regulation of PPI of the startle reflex in mice.
PMID- 17027928
TI - Voxel-based study of structural changes in first-episode patients with bipolar
disorder.
AB - BACKGROUND: Although morphometric studies of bipolar disorder (BD) suggest that
neurofunctional abnormalities reflect underlying structural changes, it remains
unclear whether abnormalities are present at illness onset or reflect disease
progression. Previous voxel-based morphometry (VBM) findings suggest that
ventrolateral prefrontal cortex (VLPFC) changes develop over time, whereas
morphologic abnormalities elsewhere in the anterior limbic network (ALN) are
present early in BD. In this study, we used VBM to explore structural brain
changes in first-episode bipolar patients. METHODS: First-episode bipolar (n =
33) and healthy (n = 33) subjects underwent magnetic resonance imaging. Images
were normalized and compared on a voxel-by-voxel basis. RESULTS: Bipolar subjects
showed no change in VLPFC density or volume. We observed increased volume in left
thalamus and fusiform and cerebellum bilaterally; increased gray matter density
in anterior cingulate and posterior parietal structures; and increased gray
matter volume and density in middle/superior temporal and posterior cingulate
gyri. No areas of decreased volume or density were observed. CONCLUSIONS: These
data indicate that structural changes are absent from VLPFC early in the course
of BD. Morphologic abnormalities are present in other portions of the ALN and in
structures previously observed to mediate neurofunctional changes in BD,
suggesting that dysfunctional neuronal proliferation or pruning may occur in
bipolar patients.
PMID- 17027929
TI - Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling
pairs from the OCD Collaborative Genetics Study.
AB - BACKGROUND: Identification of familial, more homogenous characteristics of
obsessive-compulsive disorder (OCD) may help to define relevant subtypes and
increase the power of genetic and neurobiological studies of OCD. While factor
analytic studies have found consistent, clinically meaningful OCD symptom
dimensions, there have been only limited attempts to evaluate the familiality and
potential genetic basis of such dimensions. METHODS: Four hundred eighteen
sibling pairs with OCD were evaluated using the Structured Clinical Interview for
DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist
and Severity scales. RESULTS: After controlling for sex, age, and age of onset,
robust sib-sib intraclass correlations were found for two of the four YBOCS
factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I
(aggressive, sexual, and religious obsessions, and checking compulsions; p =
.002). Smaller, but still significant, familiality was found for Factor III
(contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p =
.04). Limiting the sample to female subjects more than doubled the familiality
estimates for Factor II (p = .003). Among potentially relevant comorbid
conditions for genetic studies, bipolar I/II and major depressive disorder were
strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence,
and bulimia were associated with Factor II (p < .01). CONCLUSIONS: Factor
analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some
gender-dependence, exhibit relatively specific relationships to comorbid
psychiatric disorders and thus may be useful as refined phenotypes for molecular
genetic studies of OCD.
PMID- 17027930
TI - Regional cerebral glucose metabolic abnormalities in bipolar II depression.
AB - BACKGROUND: Functional neuroimaging studies of bipolar disorder (BD) performed in
conjunction with antidepressant treatment trials generally require that patients
remain on mood stabilizers to reduce the risk of inducing mania; yet, it is
unknown whether the metabolic abnormalities evident in unmedicated BD depressives
remain detectable in patients receiving mood stabilizers. This study investigated
whether cerebral metabolic abnormalities previously reported in unmedicated BD
subjects are evident in depressed bipolar disorder type II (BD II) subjects
receiving lithium or divalproex. METHODS: Using [18F]-fluorodeoxyglucose-positron
emission tomography, cerebral glucose metabolism was compared between 13
depressed BD II subjects on therapeutic doses of lithium or divalproex and 18
healthy control subjects. Regional metabolism was compared between groups in
predefined regions of interest. RESULTS: Metabolism was increased in the
bilateral amygdala, accumbens area, and anteroventral putamen, left orbitofrontal
cortex and right pregenual anterior cingulate cortex in depressives versus
control subjects. Post hoc exploratory analysis additionally revealed increased
metabolism in left parahippocampal, posterior cingulate, and right anterior
insular cortices in depressives versus control subjects. Correlational analyses
showed multiple limbic-cortical-striatal interactions in the BD sample not
evident in the control sample, permitting sensitive and specific classification
of subjects by discriminant analysis. CONCLUSIONS: These results confirm previous
reports that bipolar depression is associated with abnormally increased
metabolism in the amygdala, ventral striatum, orbitofrontal cortex, anterior
cingulate, and anterior insula, and extend these results to bipolar disorder type
II depressives on lithium or divalproex. They also implicate an extended
functional anatomical network known to modulate visceromotor function in the
pathophysiology of BD II depression.
PMID- 17027931
TI - Increased amygdala and decreased dorsolateral prefrontal BOLD responses in
unipolar depression: related and independent features.
AB - BACKGROUND: Major depressive disorder is characterized by increased and sustained
emotional reactivity, which has been linked to sustained amygdala activity. It is
also characterized by disruptions in executive control, linked to abnormal
dorsolateral prefrontal cortex (DLPFC) function. These mechanisms have been
hypothesized to interact in depression. This study explored relationships between
amygdala and DLPFC activity during emotional and cognitive information processing
in unipolar depression. METHOD: Twenty-seven unmedicated patients with DSM-IV
unipolar major depressive disorder and 25 never-depressed healthy control
subjects completed tasks requiring executive control (digit sorting) and
emotional information processing (personal relevance rating of words) during
event-related functional magnetic resonance imaging (fMRI) assessment. RESULTS:
Relative to control subjects, depressed subjects displayed sustained amygdala
reactivity on the emotional tasks and decreased DLPFC activity on the digit
sorting task. Decreased relationships between the time-series of amygdala and
DLPFC activity were observed within tasks in depression, but different depressed
individuals showed each type of bias. CONCLUSIONS: Depression is associated with
increased limbic activity in response to emotional information processing and
decreased DLPFC activity in response to cognitive tasks though these may reflect
separate mechanisms. Depressed individuals also display decreased relationships
between amygdala and DLPFC activity, potentially signifying decreased functional
relationships among these structures.
PMID- 17027932
TI - Beliefs and interest in cancer risk in an underserved Latino cohort.
AB - OBJECTIVE: To measure beliefs about cancer causation, cancer screening behaviors,
access to information about and resources for cancer screening, and interest in
cancer genetics services in two underserved predominantly Latino communities.
METHODS: An anonymous survey, in both English and Spanish, was distributed at the
registration desk to all attendees of selected general medicine clinics in two
underserved healthcare systems. RESULTS: There were a total of 312 respondents,
representing 98% of eligible candidates. The reported data focus on 75.3% (n=235)
of Latino respondents; mean age 43 years; 78% female; 72% less than high school
education. Heredity was perceived as the most frequent cause of cancer, after
smoking. Only 37% knew of free cancer screening programs. Over 85% expressed
interest in obtaining information about personal cancer risk and motivation to
participate in cancer genetics services. CONCLUSIONS: The results of this survey
demonstrate an awareness of heredity as a potential cause of cancer. The observed
high level of interest in cancer genetics services suggests the acceptability of
cancer genetics services in this predominantly underserved Latino population.
Furthermore, cancer genetics services would likely augment awareness and
utilization of available cancer screening services in the community.
PMID- 17027933
TI - Phonemic restoration in a sentence context: evidence from early and late ERP
effects.
AB - When a particular speech sound is obliterated and replaced by a non-speech sound
in continuous speech the listener may not notice any disturbance in speech or
have difficulties in understanding the word. The present study examined for the
first time neurophysiological correlates of the perception of words with an
obliterated initial phoneme. Behavioral responses and event-related potentials
(ERPs) were measured while participants listened to naturally spoken sentences
which had a highly or less expected final word. Half of the sentences were
manipulated to have a cough replacing the beginning of the final word, thus,
reducing the initial phonetic information available for the word recognition. An
N1-P2 complex indicated an automatic registration of the cough's onset. An early
negativity to less expected relative to highly expected words was observed for
phonetically intact words but not for manipulated words. Although the N400 effect
to manipulated words was elicited later than to intact words, after the fragment
onset, its amplitude was not enhanced. Further, no significant enhancement of the
N400 was found for the manipulated highly expected words. This finding, together
with behavioral results, indicated an easier integration of the manipulated
highly expected words with the sentence context than of intact but less expected
words. Taken together, the study demonstrates an efficient usage of both a
context-driven expectancy of the suitable word as well as a stimulus-driven
processing of the phonetic information during online perception of speech. The
present ERP results support the earlier behavioral research in showing that
phonemic restoration is not a bottom-up phenomenon but rather reflects a top-down
repair process.
PMID- 17027935
TI - Correcting for false alarms in a simple reaction time task.
AB - Simple reaction times (RTs) constitute an important source of information and
tool in human and animal psychophysics, in cognitive neuroscience, and in the
clinic. We measure simple RTs to auditory stimuli, in a high signal rate
vigilance design, to examine the possibility that simple RT may be used as a tool
to study mechanisms of temporal summation at absolute threshold. By means of
catch trials, we monitor the subjects' tendencies to produce false alarms, that
is reactions not controlled by the reaction stimulus. Here we examine the
possibility that a model of a race between a stimulus-controlled reaction process
and a false alarm process can account for the numbers as well as for the timing
of early and late RTs on stimulus trials in our experiments. We show that the
responses in both tails of our empirical RT distributions on stimulus trials are
indeed correctly predicted by the race model and can be considered false alarms.
This suggests that the race model might also provide a reasonable description of
the way in which false alarms and stimulus-controlled reactions combine when they
overlap in time. We examine the magnitudes of the estimated effects of false
alarms on several parameters of the RT distributions by application of the race
model. The analyses reveal that the effects not only vary with false alarm rate
but also with stimulus parameters. Our data suggest that the race model may
provide a theoretically reasonable and easy means of correcting for false alarms
in simple RT paradigms and thus may constitute a useful alternative to the common
practice of truncation.
PMID- 17027934
TI - MCH-containing neurons in the hypothalamus of the cat: searching for a role in
the control of sleep and wakefulness.
AB - Neurons that utilize melanin-concentrating hormone (MCH) and others that employ
hypocretin as neurotransmitter are located in the hypothalamus and project
diffusely throughout the CNS, including areas that participate in the generation
and maintenance of the states of sleep and wakefulness. In the present report,
immunohistochemical methods were employed to examine the distribution of MCHergic
and hypocretinergic neurons. In order to test the hypothesis that the MCHergic
system is capable of influencing specific behavioral states, we studied Fos
immunoreactivity in MCH-containing neurons during (1) quiet wakefulness, (2)
active wakefulness with motor activity, (3) active wakefulness without motor
activity, (4) quiet sleep and (5) active sleep induced by carbachol (AS
carbachol). We determined that MCHergic neuronal somata in the cat are
intermingled with hypocretinergic neurons in the dorsal and lateral hypothalamus,
principally in the tuberal and tuberomammillary regions; however, hypocretinergic
neurons extended more in the anterior-posterior axis than MCHergic neurons.
Axosomatic and axodendritic contacts were common between these neurons. In
contrast to hypocretinergic neurons, which are known to be active during motor
activity and AS-carbachol, Fos immunoreactivity was not observed in MCH
containing neurons in conjunction with any of the preceding behavioral
conditions. Non-MCHergic, non-hypocretinergic neurons that expressed c-fos during
active wakefulness with motor activity were intermingled with MCH and hypocretin
containing neurons, suggesting that these neurons are related to some aspect of
motor function. Further studies are required to elucidate the functional sequela
of the interactions between MCHergic and hypocretinergic neurons and the
phenotype of the other neurons that were active during motor activity.
PMID- 17027937
TI - Effect of orofacial motor cortex stimulation on neuronal activity in the red
nucleus.
AB - We studied modulation of the activities of the red nucleus (RN) neurons under to
electrical stimulation of the orofacial motor cortex (OfM) in urethane
anesthetized rats. Of 57 neurons studied, 30 (53%) neurons modulated the firing
patterns. The firing patterns of the RN neurons were classified into four types:
an excitation (E) type (n=4), a long inhibition (LI) type (n=4), a short
inhibition (SI) type (n=22), and a no-effect type (n=27). These modulated neurons
were intermingled in the dorso-ventral part of the RN. Our results suggest that
the RN neurons receive excitatory or inhibitory inputs from the OfM.
PMID- 17027936
TI - Subchronic administration of L-DOPA to adult rats with a unilateral 6
hydroxydopamine lesion of dopamine neurons results in a sensitization of enhanced
GABA release in the substantia nigra, pars reticulata.
AB - L-DOPA is the most effective pharmacological agent used for the symptomatic
treatment of Parkinson's disease but long-term L-DOPA treatment induces
involuntary abnormal movements such as dyskinesias. The present study, using in
vivo microdialysis, investigated the effects of a single or subchronic
administration of L-DOPA to adult rats with a unilateral 6-OHDA lesion of
dopamine neurons on GABA release in the substantia nigra, pars reticulata (SNr).
The results indicate that a challenge injection of L-DOPA (50 mg/kg, i.p.)
significantly increases GABA levels in the SNr of rats treated with a daily
repeated administration of L-DOPA (50 mg/kg, i.p.). Further statistical analysis
between groups also showed that extracellular GABA levels were significantly
higher in the subchronic L-DOPA group than in the group receiving only one
injection of L-DOPA. These results show that the subchronic administration of L
DOPA results in a sensitization of enhanced extracellular GABA levels in the SNr.
PMID- 17027938
TI - Fracture strength of direct versus indirect laminates with and without fiber
application at the cementation interface.
AB - OBJECTIVES: This study compared the fracture strength of direct and indirect
resin composite laminate veneers and evaluated the effect of a bidirectional E
glass woven fiber application at different locations at the cementation
interface. METHODS: Standard preparations on canines (N=50, 10 per group) were
made using a depth cutting bur (0.7mm depth) designed for laminate veneer
restorations. Forty indirect laminates using a highly filled polymeric material
(Estenia) and 10 direct laminates (Quadrant Anterior Shine) were prepared
according to the manufacturer's instructions. Bidirectional E-glass woven-fiber
sheet (0.06mm) (Everstick) was applied at different locations at the cementation
interface. The control group received no fibers. The specimens were stored in
water at 37 degrees C for 1 month prior to fracture testing performed in a
universal testing machine where the load was applied from the incisal direction
at 137 degrees (1mm/min). RESULTS: No significant differences were found between
the five groups (P>0.01) (one-way ANOVA). While indirect laminate veneers showed
mean fracture strength of 247+/-47N, direct laminate veneers revealed 239+/-104N.
The use of E-glass fibers at the cementation interface at different locations did
not increase the fracture strength significantly (286-313N) (P>0.01). Failure
analysis showed mainly cohesive fracture of the veneer restoration (20/50) and
adhesive failure between the cementation interface and the laminate with fiber
exposure (19/50) covering more than half of the restorations. SIGNIFICANCE:
Direct and indirect resin composite laminate veneers showed comparable mean
fracture strengths. The use of E-glass woven-fiber sheet at the cementation
interface did not increase the fracture strength of the polymeric laminate
veneers.
PMID- 17027939
TI - Shrinkage stress in light-cured composite resins: influence of material and
photoactivation mode.
AB - OBJECTIVES: The aim of this study was to record the effect of composite type and
photoactivation mode on the stresses resulting from polymerization of five
established composite resins: packable (Solitaire, Solitaire 2), micro-hybrid
(Aelitefil, Z100) and hybrid (Clearfil AP-X). METHODS: A mechanical testing
machine was used to record the polymerization contraction stress (MPa) of
cylindrical composite specimens (d=5mm; h=2mm; C-factor=1.25) at 0.1s intervals
over a period of 400s. The samples were photopolymerized using a halogen light
curing device under two types of light exposure: group 1, Standard (800mW.cm(
2)x60s); group 2, Exponential (logarithmic increase from 150 to 800mW.cm(-2) over
15s+800mW.cm(-2)x45s). The stress rate (SR: slope(MPa>0-60s)) and the maximum
shrinkage stress (MSS: MPa(400s)) of each material (five replications) were
statistically analysed by one-way ANOVA/Scheffe's test and Pearson's correlation
procedure (alpha=0.05). Finally, Student's t-test (two matched series) enabled
the assessment of the effect of the irradiation method on the results. RESULTS:
For group 1, in decreasing order, the MSS was 1.51+/-0.07MPa (Solitaire)
statistically equivalent to 1.45+/-0.06MPa (Aelitefil), 1.29+/-0.08MPa (Solitaire
2), and 1.04+/-0.03MPa (Z100) statistically equivalent to 0.92+/-0.05MPa
(Clearfil AP-X). Z100 showed the highest SR (0.045+/-6x10(-3)) and Solitaire, the
lowest (0.017+/-2x10(-3)). There was no correlation between SR and MSS (r<-0.33,
p<0.05). For group 2, the MSS and SR values were distributed in a similar way to
those from group 1. There was a negative correlation between SR and MSS (r<-0.43
and p<0.01). The exponential ramp successfully reduced the MSS (-3.9%) and SR (
11%) values. SIGNIFICANCE: There is no relationship between composite resin type,
stress rate and shrinkage stress levels. The slower stress rate development,
resulting from ramped light intensity, helped slightly to reduce the maximum
polymerization stress.
PMID- 17027940
TI - Synthesis of novel 2-phenylsulfonylhydrazono-3-(2',3',4',6'-tetra-O-acetyl-beta-d
glucopyranosyl)thiazolidine-4-ones from thiosemicarbazide precursors.
AB - To develop novel biologically active organic compounds possessing a sugar moiety,
a series of 2-phenylsulfonylhydrazono-3-(2',3',4',6'-tetra-O-acetyl-beta-d
glucopyranosyl)thiazolidine-4-one were synthesized via reaction of the
thiosemicarbazide with ethyl bromoacetate. Their chemical structures were
characterized by (1)H and (13)C NMR spectroscopy, elemental analysis and MS. The
bioassay results indicated that some of these compound exhibit moderate
fungicidal and herbicidal activities. Furthermore, the effect of various solvents
at reflux temperature on the reactions of ethyl bromoacetate with the related
thiosemicarbazides was investigated.
PMID- 17027941
TI - Spacer-separated sialyl LewisX cyclopeptide conjugates as potential E-selectin
ligands.
AB - Completely protected sialyl LewisX azide was synthesized from a neolactosamine
azide precursor carrying a 3-O-allyloxycarbonyl group as the temporary protecting
group. After its Pd(0)-catalyzed deprotection and stereoselective alpha
fucosylation, the obtained LewisX azide was subjected to O-deacetylation in the
galactose unit and subsequent regio- and stereoselective sialylation. Reduction
of the anomeric azido group afforded the sialyl LewisX amine building block. Two
molecules of this tetrasaccharide ligand were conjugated to a preformed
cyclooctapeptide containing two equidistant l-asparagine units equipped with
carboxy-terminated tetraethyleneglycol side chains to give, after deprotection,
the target glycopeptide conjugate. Preliminary biological evaluation of the
synthesized bivalent sialyl LewisX cyclopeptide conjugate showed only slightly
enhanced inhibition of E-selectin binding in spite of the given flexibility of
the two linked saccharide determinants.
PMID- 17027942
TI - Synthesis, characterization and thermal sensitivity of chitosan-based graft
copolymers.
AB - Novel chitosan-based graft copolymers (CECTS-g-PDMA) were synthesized through
homogeneous graft copolymerization of (N,N-dimethylamino)ethyl methacrylate (DMA)
onto N-carboxyethylchitosan (CECTS) in aqueous solution by using ammonium
persulfate (APS) as the initiator. The effect of polymerization variables,
including initiator concentration, monomer concentration, reaction time and
temperature, on grafting percentage was studied. XRD, FTIR, DSC and TGA were used
to characterize the graft copolymers. Surface-tension measurements, turbidity
measurements and temperature-variable (1)H NMR analysis were combined to
investigate the thermal sensitivity of CECTS-g-PDMAs in aqueous solution.
PMID- 17027943
TI - Evaluation of thioglycosides of Kdo as glycosyl donors.
AB - The use of Kdo thioglycosides as glycosyl donors using DMTST, IBr/AgOTf and
NIS/AgOTf as promoters has been evaluated. Activation at low temperature allowed
to escape the formation of 2,3-glycal byproducts to give glycosides in high yield
and with good beta-anomeric selectivity. The use of diethyl ether as solvent and
(especially) isopropylidene acetals as protecting groups improved the alpha
anomeric selectivity. NIS/AgOTf as promoter surprisingly yielded the 3-iodo
product via the glycal intermediate.
PMID- 17027944
TI - Mechanisms of the in vivo inhibition of calcification of bioprosthetic porcine
aortic valve cusps and aortic wall with triglycidylamine/mercapto bisphosphonate.
AB - Heart valve replacements fabricated from glutaraldehyde (Glut)-crosslinked
heterograft materials, porcine aortic valves or bovine pericardium, have been
widely used in cardiac surgery to treat heart valve disease. However, these
bioprosthetic heart valves often fail in long-term clinical implants due to
pathologic calcification of the bioprosthetic leaflets, and for stentless porcine
aortic valve bioprostheses, bioprosthetic aortic wall calcification also
typically occurs. Previous use of the epoxide-based crosslinker, triglycidyl
amine (TGA), on cardiac bioprosthetic valve materials demonstrated superior
biocompatibility, mechanics, and calcification resistance for porcine aortic
valve cusps (but not porcine aortic wall) and bovine pericardium, vs. Glut
prepared controls. However, TGA preparation did not completely prevent long-term
calcification of cusps or pericardium. Herein we report further mechanistic
investigations of an added therapeutic component to this system, 2
mercaptoethylidene-1,1-bisphosphonic acid (MABP), a custom synthesized thiol
bisphosphonate, which has previously been shown in a preliminary report to
prevent bioprosthetic heterograft biomaterial calcification when used in
combination with initial TGA crosslinking for 7 days. In the present studies, we
have further investigated the effectiveness of MABP in experiments that examined:
(1) The use of MABP after optimal TGA crosslinking, in order to avoid any
competitive interference of MABP-reactions with TGA during crosslinking; (2)
Furthermore, recognizing the importance of alkaline phosphatase (ALP) in the
formation of dystrophic calcific nodules, we have investigated the hypothesis
that the mechanism by which MABP primarily functions is through the reduction of
ALP activity. Results from cell-free model systems, cell culture studies, and rat
subcutaneous implants, show that materials functionalized with MABP after TGA
crosslinking have reduced ALP activity, and in vivo have no significant
calcification in long-term implant studies. It is concluded that bioprosthetic
heart valves prepared in this fashion are compelling alternatives for Glut
prepared bioprostheses.
PMID- 17027945
TI - A Nd:YAG laser-microperforated poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-basal
membrane matrix composite film as substrate for keratinocytes.
AB - Epithelia cultured for the treatment of ulcers, burns and for gene therapy
applications require a flexible biomaterial for growth and transplantation that
is adaptable to body contours. We tested several materials and found that a
poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) polyester provided support
for keratinocytes, although adhesion to this material proved to be suboptimal.
Since epithelia adhere to the mesoderm through basal membranes, we engineered a
basal membrane surrogate by preparing composites of PHBHV with basal membrane
matrix (BMM). To allow cell migration into injuried areas the polyester film was
micromachined to insert high-density micropores through a Nd:YAG laser ablation
process. These flexible composites provided firm attachment for keratinocytes
from the outer root sheath of human hair allowing keratinocyte migration through
micropores. Films of microperforated PHBHV-BMM may be of use for the replacement
of diseased or injured skin epithelia.
PMID- 17027946
TI - Effects of oral dosing paradigms (gavage versus diet) on pharmacokinetics and
pharmacodynamics.
AB - In cancer chemopreventive studies, test agents are typically administered via
diet, while the preclinical safety studies normally employ oral gavage dosing.
Correspondence in pharmacokinetic and pharmacodynamic profiles between the two
dosing approaches cannot be assumed a priori. Sulindac, a non-steroidal anti
inflammatory agent with potential chemopreventive activity, was used to assess
effects of the two oral dosing paradigms on its pharmacokinetics and
pharmacodynamics. Time-dependent concentrations of sulindac and its sulfone
metabolite were determined in plasma and potential target organ, mammary gland.
Prostaglandin E(2) was used as a pharmacodynamic biomarker and measured in
mammary gland. An inverse linear relationship was detected between
pharmacodynamic and pharmacokinetic markers, area under the curve for
prostaglandin E(2) levels and sulindac sulfone concentrations, respectively, in
the mammary tissue. Marked differences in pharmacokinetics and pharmacodynamics
were observed after administration of sulindac by the two oral dosing paradigms.
In general, oral gavage resulted in higher peak and lower trough concentrations
of sulindac in plasma and mammary tissue, higher area under concentration-time
curve in plasma and mammary tissue, and greater effect on prostaglandin E(2)
levels than the corresponding diet dosing. This study illustrates potential
pitfalls and limitations in trying to generalize based on data obtained with
different oral dosing schemes and their extrapolation to potential efficacy and
health risks in humans.
PMID- 17027947
TI - Functional characterization of human and cynomolgus monkey UDP
glucuronosyltransferase 1A6 enzymes.
AB - UDP-glucuronosyltransferase 1A6 (UGT1A6) is a major isoform in the human liver
that glucuronidates numerous drugs, environmental chemicals and endogenous
substrates. In this study, human and cynomolgus monkey UGT1A6 cDNAs (humUGT1A6
and monUGT1A6, respectively) were cloned, and the corresponding proteins were
heterologously expressed in yeast cells to identify the functions of primate
UGT1A6s. The enzymatic properties of UGT1A6 proteins were characterized by the
kinetic analysis of serotonin (5-hydroxytryptamine, 5-HT) and 4
methylumbelliferone (4-MU) glucuronidation. humUGT1A6 and monUGT1A6 showed 96%
identity in their nucleotide and amino acid sequences. Immunoblotting analysis
using an antibody raised against human UGT1A6 showed that protein staining
intensities were different between human and cynomolgus monkey UGT1A6 enzymes in
microsomal fractions from livers and yeast cells, although both enzymes were
detectable. The apparent K(m) value (15 mM) for 5-HT glucuronidation of
cynomolgus monkey liver microsomes was significantly higher than that (8.6mM) of
human liver microsomes, whereas V(max) values were lower in cynomolgus monkeys
(2.8 nmol/min/mg protein) than in humans (8.6 nmol/min/mg protein). No
significant species difference was observed in K(m) (approximately 90 microM) or
V(max) (approximately 25 nmol/min/mg protein) values for liver microsomal 4-MU
glucuronidation. In yeast cell microsomes, K(m) values (approximately 6mM) for 5
HT glucuronidation by recombinant UGT1A6s were similar, while a V(max) value
(0.1nmol/min/mg protein) of monUGT1A6 was significantly lower than that (0.7
nmol/min/mg protein) of humUGT1A6. In 4-MU glucuronidation, both K(m) (210
microM) and V(max) (3.5 nmol/min/mg protein) values of monUGT1A6 were
significantly higher than those of humUGT1A6 (K(m), 110 microM; V(max),
1.5nmol/min/mg protein). These findings suggest that the enzymatic properties of
UGT1A6 were extensively different between humans and cynomolgus monkeys, although
humUGT1A6 and monUGT1A6 showed high homology at the amino acid level. The
information gained in this study should help with in vivo extrapolation and to
assess the toxicity of xenobiotics.
PMID- 17027948
TI - Phase behaviour of stearic acid-stearonitrile mixtures. A thermodynamic study in
bulk and at the air-water interface.
AB - The solid-liquid phase behaviour of stearic acid (SA) and stearonitrile (SN) in
binary mixtures was investigated by differential scanning calorimetry (DSC), and
the formation of SA-SN mixed monolayers at the air-water interface was followed
by surface pressure-area (pi-A) measurements and by Brewster angle microscope
(BAM) observation. The solid-liquid phase diagram is a eutectic type phase
diagram, with the eutectic composition 0.90or=10 microg/dl and anemia in children. We performed a cross-sectional
study to evaluate the association of blood lead levels>or=10 microg/dl with
anemia, and its effect on hematological system and some essential trace metals in
children. METHODS: A total of 75 children aged 1-7 years, 50 anemic (Hb8 g%), drawn from Lucknow, India and nearby areas were
recruited to determine blood levels of lead, iron, zinc, copper, and calcium
along with hematological parameters [delta-aminolevulinic acid dehydratase (delta
ALAD) hemoglobin (Hb), hematocrit, and ascorbic acid]. RESULTS: Based on Centre
for Disease Control and Prevention's intervention level of blood lead, children
were categorized into those with blood lead<10 microg/dl (6.89+/-2.44) (n=19)
(GI) and those with blood lead<10 microg/dl (21.86+/-7.58) (n=56) (GII). After
adjustment for child's age, sex, and area of residence, children with blood lead
levels>or=10 microg/dl were 2.87 (95% CI: 1.60-2.87) times as likely to have
anemia as children with blood lead levels<10 microg/dl. The differences of the
adjusted mean values of Hb, delta-ALAD, and hematocrit were significantly lower
in children from the GII group when compared to children from the GI group
(p<0.01, p<0.01, and p<0.05, respectively). Among essential trace metals,
adjusted mean levels of blood iron, zinc, and calcium were significantly lower in
GII as compared to GI (P<0.05 each). There were significant negative correlations
of blood lead levels with delta-ALAD (r=-0.612, p<0.01), hematocrit (r=-0.427,
p<0.05), iron (r=-0.552, p<0.05) zinc (r=-0.427, p<0.05), and calcium (r=-0.324,
p<0.05). CONCLUSION: Results indicate that elevated blood lead levels (>or=10
microg/dl) in children were significantly associated with risk of anemia and that
blood lead levels also influenced the status of essential trace metals. However,
results of this study may be limited due to limited sample size but certainly
form the basis of a larger sample size study, taking into account all the known
potential confounders of anemia in children.
PMID- 17027951
TI - Comparison of plasma beta-globin DNA and S-100 protein concentrations in acute
stroke.
AB - BACKGROUND: This study aimed to compare changes in plasma beta-globin DNA and
serum S100 protein to diagnose stroke and for predicting mortality and morbidity.
METHODS: Patients with stroke-like symptoms presenting to the emergency
department of a Hong Kong hospital were recruited. Plasma DNA was analyzed for
the beta-globin gene with fluorescent-based PCR. S100 concentrations were
determined using ELISA. Primary outcomes were diagnosis of stroke, mortality, and
modified Rankin Score (mRS) after 6 months. RESULTS: One hundred ninety-seven
consecutive patients recruited, 118 (60%) ischemic stroke, 35 (18%) hemorrhage
and 44 (22%) with no acute neuroimaging changes. Serum S100 and plasma DNA were
increased in 126 (p<0.0010) and 36 (p=0.21) stroke patients respectively vs.
controls. Median plasma DNA was higher in hemorrhagic stroke than those without
(1725 vs. 1050 kilogenome-equivalents/l, p=0.0104). Median plasma DNA was higher
in mRS>2 vs. mRS2 patients
vs. mRS 0.99). The developed method was applicable for the analysis of the beta
agonists in syrup and tablets and the NACE condition was compatible with a mass
spectrometer detector.
PMID- 17027996
TI - Simple and environmental friendly procedure for the gas chromatographic-mass
spectrometric determination of caffeine in beverages.
AB - A simple, quick and organic solvent saving procedure has been developed for the
GC/MS determination of caffeine in beverages. The procedure involves the mixing
of 25 microL sample with 1 mL ethyl acetate, and a following simple desiccation
procedure in a 1.5 mL autosampler vial. A linear calibration curve was generated
with caffeine concentration ranging from 0.005 mg/L to 30.0mg/L. The procedure
developed provides a 0.001 mg/L detection limit of caffeine in the final solution
by injection of 1 microL solution and the relative standard deviation (RSD) was
less than 2% for independent measurement. The total amount of organic solvent
used for individual detection is 1 mL of nontoxic ethyl acetate. The developed
method was repeatable and could be applied to determine trace amounts of caffeine
in popular commercial beverages.
PMID- 17027997
TI - Improved and simplified liquid chromatography/atmospheric pressure chemical
ionization mass spectrometry method for the analysis of underivatized free amino
acids in various foods.
AB - An improved analytical method which offers rapid, accurate determination and
identification of 22 amino acids in a variety of matrices, e.g. baby foods,
juices, honey is reported. The amino acids were extracted from the matrixes using
acidified water. Simultaneous determination of 22 underivatized amino acids was
carried out by a liquid chromatography-mass spectrometry (LC/MS). A narrow-bore
column allowed rapid screening and quantitative analysis by positive
LC/atmospheric pressure chemical ionization (APCI) MS with only acidified mobile
phase. Retention times of the 22 amino acids were in the range of ca. 0.9-7.5
min. Sample preparation without clean-up followed by fast chromatographic
analysis allowed the analysis to be completed in <25 min.
PMID- 17027998
TI - Chromatographic separation of certain metal ions using a bifunctional quaternary
ammonium-sulfonate mixed bed ion-exchanger.
AB - The separation behaviour of Pb(2+), Cu(2+), Cd(2+), Co(2+), Zn(2+) and Ni(2+) on
bifunctional quaternary ammonium-sulfonate mixed ion-exchangers (Dionex, IonPac
CS5 and CG5) was studied using different eluents including solutions of oxalic
acid, potassium oxalate, sodium oxalate and ammonium oxalate. Separated metal
ions were followed by using 4-(2-pyridylazo) resorcinol (PAR) as post-colouring
complex. The retention factors of different ions proved to be dependent on the
pH, concentration, nature of each complexing agent, and to less extent on eluent
flow rate. The retention behaviour and separation mechanism of complexed metal
analytes are discussed in the light of the stability of metal complexes and the
ligand complexing ability of used eluent. Comparison between various mobile
phases is evaluated, and both sodium and potassium oxalate can be used
successfully for simultaneous separation of studied metals with good resolution
within short elution periods. The method can be used in different applications
including analysis of bottled water from different resources.
PMID- 17027999
TI - 4-(4'-Methyltetrafluorophenyl)-2,3,5,6-tetrafluorobenzyl bromide: a new
electrophoric derivatizing reagent.
AB - Commercially-available 4,4'-dimethyloctafluorobiphenyl was converted in a single
step to 4-(4'-methyltetrafluorophenyl)-2,3,5,6-tetrafluorobenzyl bromide (MTFP
TFBBr) for the purpose of providing a new electrophoric derivatizing reagent.
When reacted with this reagent, 2-fluoro-O6-(2'-hydroxyethyl)hypoxanthine, a
model analyte, gave a mixture of isomeric products (apparently substituted at N7
and N9, analogous to its known reaction with pentafluorobenzyl bromide), and 53
femtograms of the mixture was detected at S/N = 10 by gas chromatography electron
capture mass spectrometry (GC-EC-MS). As intended, the volatility of the MTFB
TFBBr derivative was much less (two-fold) than that of the corresponding
pentafluorobenzyl derivative. It is anticipated that MTFB-TFBBr sometimes will be
useful in providing an electrophoric derivative that encounters less background
noise in analysis by electrophore derivatization/GC-EC-MS.
PMID- 17028000
TI - Classification and dating of black gel pen ink by ion-pairing high-performance
liquid chromatography.
AB - A novel approach for classification and dating of the black gel pen ink entries
on document was developed based on ion-pairing high-performance liquid
chromatography (IP-HPLC). Ninety-three black gel pens were collected and divided
into two groups, dye-based and pigment-based, by preliminary solubility test. The
chromatographic conditions for separation of the dye-based black gel pen inks
were optimized and the dye components in inks were satisfactorily separated by
using 40 mmol/L tetrabutylammonium bromide as ion-pairing reagent. According to
the number and the chromatographic retention times of the main dye components,
the 50 dye-based inks were categorized into four classes. The inks within a class
can be further identified by the percentage of each dye component. The
compositional changes of the dye components in the black gel pen ink entries on
paper were investigated in light and natural aging conditions and it has been
found that the dye components in the ink entries underwent obvious decomposition,
and the decomposing extent of the dye components was related to the aging time.
The results can provide scientific evidences for dating of the suspicious black
gel pen ink entries on documents.
PMID- 17028001
TI - Rapid determination of short chain carnitines in human plasma by electrospray
ionisation-ion trap mass spectrometry using capillary electrophoresis instrument
as sampler.
AB - A capillary electrophoresis apparatus was used as sampler for flow injection
analysis (FIA) in tandem mass spectrometry of L-carnitine and its acetyl- and
propionyl-metabolites in human plasma. The capillary electrophoresis instrument
was coupled to the ion trap mass spectrometer by an electrospray ionization
coaxial sheath liquid interface. The electrophoresis capillary introduced the
sample directly into the source by applying a prolonged sample injection. The use
of the capillary electrophoresis apparatus miniaturised the FIA procedure,
substantially reducing the quantities of solvents and samples used, and allowed
rapid automated sequential analyses. The method was optimised and validated using
a dialyzed human plasma matrix. The plasma samples were analysed after a simple,
rapid deproteinisation procedure with acetonitrile and diluted 70 times before
direct injection into the mass spectrometer for product ion scan MS/MS analysis
in positive ionisation. The total analysis time was 5 min, including capillary
preconditioning and acquisition time (3 min). The method was sensitive, allowing
the determination of L-, L-acetyl- and L-propionyl-carnitines at 140, 14 and 3.6
nM concentrations (injected values) corresponding to lower limit of quantitation
values in plasma of 10, 1 and 0.25 microM, respectively. The method was processed
for full validation and applied to the analysis of L-carnitine and its short
chain derivatives in human plasma samples.
PMID- 17028002
TI - Activational levels of androgens influence risk assessment behaviour but do not
influence stress-induced suppression in hippocampal cell proliferation in adult
male rats.
AB - Adult male, but not female, rats demonstrate a suppression in hippocampal cell
proliferation in response to an acute predator odour stress. The present study
examined the effect of activational levels of androgens on stress-induced changes
in hippocampal cell proliferation and defensive and non-defensive behaviours in
adult male rats. Adult male Sprague-Dawley rats were castrated and exposed to
trimethylthiazoline (TMT, the main component of fox feces). Androgen status did
not significantly affect TMT-induced suppression in hippocampal cell
proliferation or expression of defensive burying. However, castrated males did
not show an increase in duration of stretch attends (a risk assessment behaviour)
in response to TMT. The results of this study suggest that activational levels of
androgens in the male rat do not directly regulate the sex difference in stress
induced suppression of hippocampal cell proliferation but do regulate risk
assessment behaviour.
PMID- 17028003
TI - Nozzle and liquid effects on the spray modes in nanoelectrospray.
AB - Unforced nanoelectrospray can exhibit a number of stable spray modes. These
include low frequency pulsations, high frequency pulsations, and a steady cone
jet. Experiments are reported here on such pulsations that have been observed in
various salt loaded solutions of ethylene glycol, triethylene glycol and water.
The spray current was monitored with 1 mus time resolution to show that spray
regime characteristics depend on nozzle diameter and liquid conductivity. The
frequency of pulsations was found to increase with both increased liquid
conductivity and decreasing nozzle diameter. The charge ejected during a pulse is
lower for smaller nozzles spraying higher conductivity liquids. Water solutions
were observed undergoing high frequency pulsations, with these pulsations often
occurring in lower frequency bursts. The frequencies of water pulsations were as
high as 635 kHz but the charge ejected by each pulsation was an order of
magnitude lower than that observed in triethylene glycol. An unforced
electrospray of water was also identified as being in the steady cone-jet mode
with a higher degree of confidence than previously. The values for stable
pulsation frequency and charge ejected observed in ethylene glycol lay between
those of TEG and water.
PMID- 17028004
TI - Microwave-assisted synthesis of anhydrous CdS nanoparticles in a water-oil
microemulsion.
AB - Microwave irradiation at a frequency of 2.45 GHz and a power ranging between 22
and 30 W was used, in a water-oil microemulsion at 35+/-2 degrees C, to obtain
stable, small, crystalline, anhydrous CdS nanoparticles exhibiting enhanced
luminescence properties. The process of nanoparticles growth at different
irradiation times was followed by UV-vis spectroscopy. It was observed that
irradiated nanoparticles grew faster and their size reached a constant value. The
final mean nanoparticle diameter was 2.7 nm, smaller than that observed in a non
irradiated sample, in which particle dimensions slowly increased even after 10 h.
This finding was confirmed by high resolution transmission electron microscopy
which also suggested that the spherical nanoparticles had a narrow size
distribution and were spatially well separated. Furthermore, Fourier transform
infrared spectroscopy was used to obtain information about structural changes
that the microemulsion underwent when irradiated by microwaves. In particular,
the evolution of the stretching and bending bands of water molecules along with
the CO and SO3 stretching bands of the surfactant molecules, showed that water
was selectively and almost completely extracted from the aqueous core of the
reversed micelles. Changes in the surroundings of the nanoparticles surface were
monitored by photoluminescence spectroscopy and variations in the emission band
profiles indicated enhanced luminescence properties. The latter finding, as well
as the inhibition of the nanoparticles growth process, are attributable to the
progressive reduction of water content in the core of the reversed micelles.
PMID- 17028006
TI - Application of a multi-dentate amphiphilic compound to transfer silver
nanoparticles into an organic solvent.
AB - A multi-dentate amphiphilic compound, 3,3'-(dodecylazanediyl)-bis-[N-(2
aminoethyl)propanamide] (12C-2NH2) has been synthesized. The molecular structure
was characterized by Fourier transform infrared (FT-IR) spectroscopy, ultraviolet
visible (UV-vis) spectra, nuclear magnetic resonance (NMR) spectra, and fast atom
bombardment mass (FAB-MS) spectra. 12C-2NH2 was employed to stabilize silver
nanoparticles. Surface properties and stability of silver nanoparticles were
controlled by adjusting the 12C-2NH2 to silver (0) molar ratio. 12C-2NH2 was also
applied to transfer silver nanoparticles from an aqueous to an organic phase. The
transfer efficiency depends on 12C-2NH2 concentration. When 12C-2NH2 to silver
(0) molar ratio was 2:1, the highest efficiency of phase transfer to toluene was
obtained. These 12C-2NH2 stabilized silver nanoparticles are very stable over a
period of four days in toluene.
PMID- 17028005
TI - Quartz crystal microbalance studies on bilirubin adsorption on self-assembled
phospholipid bilayers.
AB - Bilirubin adsorption on self-assembled phospholipid bilayers was studied using
quartz crystal microbalance, and factors influencing its adsorption such as pH,
temperature, and solution ionic strength were discussed in detail. The results
show the amount of adsorbed bilirubin on self-assembled phospholipid bilayers is
small at higher temperature and large at higher pH and solution ionic strength,
and the adsorption kinetic parameter estimated from the in situ frequency
measurement is (1.8+/-0.27)x10(6) M(-1) (mean +/- S.D.). With the present method,
the desorption of adsorbed bilirubin caused by human serum albumin and the
photoinduced decomposition of adsorbed bilirubin under light illumination were
also examined. QCM measurement provides a useful method for monitoring the
adsorption/desorption process of bilirubin on self-assembled phospholipid
bilayers.
PMID- 17028007
TI - Solvent effect on CO oxidation as a novel diagnosing tool to pin down low
coverage CO at the liquid-solid interface: An in situ infrared study.
AB - In situ probing of liquid-solid interfaces is important for understanding
heterogeneous liquid-phase catalysis and other interfacial phenomena, but the
spectroscopic interference from the bulk is often a problem. Some organics may
have infrared features overlapping the adsorbed CO peaks, making the
determination of adsorbed CO difficult. In this study, CCl4-flushing was used as
a novel diagnosing tool to pin down the low-coverage CO derived from
decarbonylation of organics. This diagnosing tool was designed based on our in
situ reflection-absorption infrared spectroscopy results reported here that there
is a marked solvent effect (water > ethanol > methanol > cyclohexane > benzene
approximately carbon tetrachloride) on CO oxidation at the liquid-solid
interface. Possible reasons for that solvent effect were discussed.
PMID- 17028008
TI - Differentiation of Leishmania major is impaired by over-expression of
pyroglutamyl peptidase I.
AB - Pyroglutamyl peptidases I (PPI) are cysteine peptidases of the clan CF, family
C15, which hydrolyse N-terminal l-pyroglutamyl residues (l-pGlu). The l-pGlu
modification is a post-transcriptional modification that confers relative
aminopeptidase resistance and, in some cases, is essential to the modified
peptides' biological activity. PPIs have been identified in a variety of
organisms, although definitive biological functions have yet to be attributed to
them. The L. major PPI was expressed in Escherichia coli as active recombinant
enzyme, and shown to have biochemical properties more similar to mammalian than
bacterial PPIs. The LmPPI active site catalytic triad of E101, C210, and H234 was
confirmed by mutagenesis. PPI activity was detected in L. major promastigotes,
and the enzyme localised to the parasite cytosol. No detectable phenotype could
be observed for L. major PPI-deficient mutants, which retained infectivity to
macrophages in vitro and mice. However, over-expression of the active PPI, but
not inactive PPI(C210A), in L. major impaired differentiation from the procyclic
promastigote to the infective metacyclic promastigote. Susceptibility to a
natural l-pGlu-modified antimicrobial peptide, gomesin, was tested using the
different cell lines, which were all equally susceptible. Whilst PPI is
widespread through the eukaryotic kingdom, this study now suggests that the
enzyme is not essential for normal eukaryotic cell function. However, PPI could
be involved in regulating the action of l-pGlu-modified peptides required for
differentiation of L. major.
PMID- 17028009
TI - Involvement of actin and myosins in Plasmodium berghei ookinete motility.
AB - Ookinetes of the genus Plasmodium are motile, invasive cells that develop in the
mosquito midgut following ingestion of a parasite-infected blood meal. We show
here that ookinetes display gliding motility on glass slides in the presence of
insect cells. Moreover, in addition to stationary "flexing" and "twirling" of the
cells, two distinct types of movements occur: productive forward translocational
motility in straight segment that progresses with an average speed of
approximately 6mum/min and rotational motility, which does not lead to forward
translocation. Locomotion is reduced by treatment with butanedione monoxime, an
inhibitor of myosin ATPase, and by three different actin inhibitors. We also
studied the expression during ookinete development of genes encoding actin and
two small class XIV myosins, PbMyoA, and PbMyoB. Western immunoblots revealed
that PbMyoA is only present in fully mature ookinetes, whilst the other two
proteins are additionally expressed in gametocytes and zygotes.
Immunofluorescence experiments reveal that MyoA and actin co-localize in the
apical tip of the parasite whereas MyoB displays a punctate pattern of expression
around the entire cell periphery. Following treatment with jasplakinolide, the
apparent level of detectable actin appears to substantially increase and becomes
concentrated in a discrete area in the basal pole of the ookinete.
PMID- 17028010
TI - Central actions of angiotensin II on spontaneous baroreflex sensitivity in the
trout Onc orhynchus mykiss.
AB - The goal of the present study was to investigate the central action of native
angiotensin II (ANG II) on the spontaneous baroreflex sensitivity (BRS) in
unanesthetized trout. The animals were equipped with two subcutaneous
electrocardiographic (ECG) electrodes, a dorsal aorta catheter and an
intracerebroventricular (ICV) cannula which was inserted within the third
ventricle of the brain. The ECG and the systolic blood pressure (SBP) signals
were recorded during a pre-injection period of 5 min and during five post
injection periods of 5 min. All injections were made at the fifth minute of the
test. The time-series were processed with a sequence technique in order to detect
the sequences of three or more consecutive increases in the SBP pulse, or three
or more decreases in the SBP pulse correlated respectively with one delay beat
increase of the RR interval of the ECG signal or shortening of this interval. The
slope of the average regression line between the SBP and the RR intervals for
each type of sequence was taken as a measure of the spontaneous BRS. Compared
with pre-injection values, the ICV injection of vehicle (0.5 microl) had no
effect on heart rate (HR), SBP, the total number of positive or negative
sequences or on the spontaneous BRS during the post-injection periods. By
contrast, ANG II at doses of 5 and 50 pmol increased HR but only 50 pmol ANG II
elevated SBP. For all doses, ANG II depressed the spontaneous BRS, but the
peptide had no effect upon the number of each baroreflex sequences. Intra
arterial injections of atropine dramatically reduced the number of positive and
negative baroreflex sequences and decreased the sensitivity of the few remaining
sequences, suggesting that the autonomic control of the cardiac BRS was solely
due to vagal parasympathetic control. In atropinized trout the ICV injection of 5
pmol ANG II had no effect upon HR, SBP and the baroreflex parameters. This study
determines for the first time the spontaneous BRS in a non-mammalian species and
demonstrates an inhibitory action of ICV injection of ANG II upon this variable
through a probable control of the vagal parasympathetic activity.
PMID- 17028011
TI - Peroxisomal beta-oxidation--a metabolic pathway with multiple functions.
AB - Fatty acid degradation in most organisms occurs primarily via the beta-oxidation
cycle. In mammals, beta-oxidation occurs in both mitochondria and peroxisomes,
whereas plants and most fungi harbor the beta-oxidation cycle only in the
peroxisomes. Although several of the enzymes participating in this pathway in
both organelles are similar, some distinct physiological roles have been
uncovered. Recent advances in the structural elucidation of numerous mammalian
and yeast enzymes involved in beta-oxidation have shed light on the basis of the
substrate specificity for several of them. Of particular interest is the
structural organization and function of the type 1 and 2 multifunctional enzyme
(MFE-1 and MFE-2), two enzymes evolutionarily distant yet catalyzing the same
overall enzymatic reactions but via opposite stereochemistry. New data on the
physiological roles of the various enzymes participating in beta-oxidation have
been gathered through the analysis of knockout mutants in plants, yeast and
animals, as well as by the use of polyhydroxyalkanoate synthesis from beta
oxidation intermediates as a tool to study carbon flux through the pathway. In
plants, both forward and reverse genetics performed on the model plant
Arabidopsis thaliana have revealed novel roles for beta-oxidation in the
germination process that is independent of the generation of carbohydrates for
growth, as well as in embryo and flower development, and the generation of the
phytohormone indole-3-acetic acid and the signal molecule jasmonic acid.
PMID- 17028012
TI - Peroxisomal matrix protein receptor ubiquitination and recycling.
AB - The peroxisomal targeting signal type1 (PTS1) receptor Pex5 is required for the
peroxisomal targeting of most matrix proteins. Pex5 recognises target proteins in
the cytosol and directs them to the peroxisomal membrane where cargo is released
into the matrix, and the receptor shuttles back to the cytosol. Recently, it has
become evident that the membrane-bound Pex5 can be modified by mono- and
polyubiquitination. This review summarises recent results on Pex5 ubiquitination
and on the role of the AAA peroxins Pex1 and Pex6 as dislocases required for the
release of Pex5 from the membrane to the cytosol where the receptor is either
degraded by proteasomes or made available for another round of protein import
into peroxisomes.
PMID- 17028013
TI - p120-ctn: A nexus for contextual signaling via Rho GTPases.
AB - p120 catenin (p120) is the prototypic member of a subfamily of armadillo repeat
domain proteins involved in intercellular adhesion. Recent evidence indicates
that p120 associates with classical cadherins and regulates their stability.
Ectopic p120 expression results in a variety of morphological effects, and
promotes cell migration. There is now strong evidence that p120 acts, at least in
part, through regulation of Rho GTPases. The data suggest that p120 may act as a
signaling nexus, conveying messages from the cellular micro- and macro
environment to the cell's interior. By regulating Rho GTPases in a context
dependent manner p120 can exert profound effects on cellular responses from
synaptic plasticity to vesicle trafficking, as well as regulate the motile vs.
sessile, and possibly the proliferative vs. quiescent phenotype of epithelial
cells. Here, we review the new evidence on the relationship of p120 to Rho
GTPases, and discuss potential roles for the p120-Rho connection in normal and
malignant cells.
PMID- 17028014
TI - PTS2 co-receptors: diverse proteins with common features.
AB - One feature of the PTS2 import pathway is the separation of the roles of the PTS
receptor between two proteins. Pex7p alone is insufficient to act as the receptor
for the import cycle for peroxisomal matrix proteins. In all cases, Pex7p needs a
PTS2 co-receptor to form an import-competent PTS2 receptor complex together with
the PTS2 cargo. We provide an overview of the proteins that have been identified
as PTS2 co-receptors and discuss their proposed functions.
PMID- 17028015
TI - Detection of allergens from Alternaria alternata by gold-conjugated anti-human
IgE and field emission scanning electron microscopy.
AB - Fungal allergens are present in viable and non-viable conidia, hyphae and fungal
fragments. It has been shown that large quantities of allergen are released from
conidia during germination. We used a gold immunolabelling technique and field
emission scanning electron microscopy to examine the allergen release from
Alternaria alternata conidia. Immunolabelling was associated with the hyphal tip
and amorphous matter associated with the emerging hyphae. Non-specific antibody
controls showed no labelling associated with germinating fungi. This suggests
that material released from hyphae may be an additional source of fungal
allergens.
PMID- 17028017
TI - Reversal of supra-systemic pulmonary pressures following mitral valve surgery in
a young girl.
PMID- 17028016
TI - Octopamine and tyramine influence the behavioral profile of locomotor activity in
the honey bee (Apis mellifera).
AB - The biogenic amines octopamine and tyramine are believed to play a number of
important roles in the behavior of invertebrates including the regulation of
motor function. To investigate the role of octopamine and tyramine in locomotor
behavior in honey bees, subjects were injected with a range of concentrations of
octopamine, tyramine, mianserin or yohimbine. Continuous observation of freely
moving worker bees was used to examine the effects of these treatments on the
amount of time honey bees spent engaged in different locomotor behaviors such as
walking, grooming, fanning and flying. All treatments produced significant shifts
in behavior. Decreases in time spent walking and increases in grooming or stopped
behavior were observed for every drug. However, the pattern of the shift depended
on drug, time after injection and concentration. Flying behavior was
differentially affected with increases in flying seen in octopamine treated bees,
whereas those receiving tyramine showed a decrease in flying. Taken together,
these data provide evidence that octopamine and tyramine modulate motor function
in the honey bee perhaps via interaction with central pattern generators or
through effects on sensory perception.
PMID- 17028018
TI - Levosimendan in acute decompensation of anthracycline-induced cardiotoxicity.
PMID- 17028019
TI - Serpin1 of Arabidopsis thaliana is a suicide inhibitor for metacaspase 9.
AB - Metacaspases are distant relatives of animal caspases found in plants, fungi and
protozoa. We demonstrated previously that two type II metacaspases of Arabidopsis
thaliana, AtMC4 and AtMC9 are Arg/Lys-specific cysteine-dependent proteases. We
screened a combinatorial tetrapeptide library of 130,321 substrates with AtMC9.
Here, we show that AtMC9 is a strict Arg/Lys-specific protease. Based on the
position-specific scoring matrix derived from the substrate library results, the
tetrapeptide Val-Arg-Pro-Arg was identified as an optimized substrate. AtMC9 had
a kcat/KM of 4.6x10(5) M-1 s-1 for Ac-Val-Arg-Pro-Arg-amido-4-methyl-coumarin,
representing a more than 10-fold improvement over existing fluorogenic
substrates. A yeast two-hybrid screen with catalytically inactive AtMC9 as bait
identified a serine protease inhibitor, designated AtSerpin1, which was found to
be a potent inhibitor of AtMC9 activity in vitro through cleavage of its reactive
center loop and covalent binding to AtMC9. On the basis of the substrate
profiling of AtMC9 and confirmation through site-directed mutagenesis, the
inhibitory P4-P1 cleavage site of AtSerpin1 was determined to be Ile-Lys-Leu
Arg351. Further mutagenesis of the AtSerpin1 inhibitory cleavage site modulated
AtMC9 inhibition positively or negatively. Both AtMC9 and AtSerpin1 were
localized in the extracellular space, suggesting an in vivo interaction as well.
To our knowledge, this is the first report of plant protease inhibition by a
plant serpin.
PMID- 17028021
TI - SOS repair and DNA supercoiling influence the genetic stability of DNA triplet
repeats in Escherichia coli.
AB - Molecular mechanisms responsible for the genetic instability of DNA trinucleotide
sequences (TRS) account for at least 20 human hereditary disorders. Many aspects
of DNA metabolism influence the frequency of length changes in such repeats.
Herein, we demonstrate that expression of Escherichia coli SOS repair proteins
dramatically decreases the genetic stability of long (CTG/CAG)n tracts contained
in plasmids. Furthermore, the growth characteristics of the bacteria are affected
by the (CTG/CAG)n tract, with the effect dependent on the length of the TRS. In
an E. coli host strain with constitutive expression of the SOS regulon, the
frequency of deletions to the repeat is substantially higher than that in a
strain with no SOS response. Analyses of the topology of reporter plasmids
isolated from the SOS+ and SOS- strains revealed higher levels of negative
supercoiling in strains with the constitutively expressed SOS network. Hence, we
used strains with mutations in topoisomerases to examine the effect of DNA
topology upon the TRS instability. Higher levels of negative DNA supercoiling
correlated with increased deletions in long (CTG/CAG)n, (CGG/CCG)n and
(GAA/TTC)n. These observations suggest a link between the induction of bacterial
SOS repair, changes in DNA topology and the mechanisms leading to genetic
instability of repetitive DNA sequences.
PMID- 17028020
TI - In meso structure of the cobalamin transporter, BtuB, at 1.95 A resolution.
AB - Crystals of the apo form of the vitamin B12 and colicin receptor, BtuB, that
diffract to 1.95 A have been grown by the membrane-based in meso technique. The
structure of the protein differs in several details from that of its counterpart
grown by the more traditional, detergent-based (in surfo) method. Some of these
differences include (i) the five N-terminal residues are resolved in meso, (ii)
residues 57-62 in the hatch domain and residues 574-581 in loop 21-22 are
disordered in meso and are ordered in surfo, (iii) residues 278-287 in loop 7-8
are resolved in meso, (iv) residues 324-331 in loop 9-10, 396-411 in loop 13-14,
442-458 in loop 15-16 and 526-541 in loop 19-20 have large differences in
position between the two crystal forms, as have residues 86-96 in the hatch
domain, and (v) the conformation of residues 6 and 7 in the Ton box (considered
critical to signal transduction and substrate transport) are entirely different
in the two structures. Importantly, the in meso orientation of residues 6 and 7
is similar to that of the vitamin B12-charged state. These data suggest that the
"substrate-induced" 180 degrees -rotation of residues 6 and 7 reported in the
literature may not be a unique signalling event. The extent to which these
findings agree with structural, dynamic and functional insights gleaned from site
directed spin labelling and electron paramagnetic resonance measurements is
evaluated. Packing in in meso grown crystals is dense and layered, consistent
with the current model for crystallogenesis of membrane proteins in lipidic
mesophases. Layered packing has been used to locate the transmembrane hydrophobic
surface of the protein. Generally, this is consistent with tryptophan, tyrosine,
lipid and CalphaB-factor distributions in the protein, and with predictions based
on transfer free energy calculations.
PMID- 17028022
TI - ATP synthase b subunit dimerization domain: a right-handed coiled coil with
offset helices.
AB - The dimerization domain of Escherichia coli ATP synthase b subunit forms an
atypical parallel two-stranded coiled coil. Sequence analysis reveals an 11
residue abcdefghijk repeat characteristic of right-handed coiled coils, but no
other naturally occurring parallel dimeric structure of this class has been
identified. The arrangement of the helices was studied by their propensity to
form interhelix disulfide linkages and analysis of the stability and shape of
disulfide-linked dimers. Disulfides formed preferentially between cysteine
residues in an a position of one helix and either of the adjacent h positions of
the partner. Such heterodimers were far more stable to thermal denaturation than
homodimers and, on the basis of gel-filtration chromatography studies, were
similar in shape to both non-covalent dimers and dimers linked through flexible
Gly(1-3)Cys C-terminal extensions. The results indicate a right-handed coiled
coil structure with intrinsic asymmetry, the two helices being offset rather than
in register. A function for the right-handed coiled coil in rotational catalysis
is proposed.
PMID- 17028023
TI - Structure of Halothiobacillus neapolitanus carboxysomes by cryo-electron
tomography.
AB - Carboxysomes are polyhedral bodies consisting of a proteinaceous shell filled
with ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO). They are found in
the cytoplasm of all cyanobacteria and some chemoautotrophic bacteria. Previous
studies of Halothiobacillus neapolitanus and Nitrobacter agilis carboxysomes
suggest that the structures are either icosahedral or dodecahedral. To determine
the protein shell structure more definitively, purified H. neapolitanus
carboxysomes were re-examined by cryo-electron tomography and scanning
transmission electron microscopy (STEM). Due to the limited tilt angles in the
electron microscope, the tomographic reconstructions are distorted. Corrections
were made in the 3D orientation searching and averaging of the computationally
extracted carboxysomes to minimize the missing data effects. It was found that H.
neapolitanus carboxysomes vary widely in size and mass as shown by cryo-electron
tomography and STEM mass measurements, respectively. We have aligned and averaged
carboxysomes in several size classes from the 3D tomographic reconstruction by
methods that are not model-biased. The averages reveal icosahedral symmetry of
the shell, but not of the density inside it, for all the size classes.
PMID- 17028024
TI - GFP technology for the study of biocontrol agents in tritrophic interactions: a
case study with Pseudozyma flocculosa.
AB - GFP technology was applied to the biocontrol agent (BCA) Pseudozyma flocculosa to
study its development and interactions at the tritrophic level plant-powdery
mildew-BCA. Transformation experiments with GFP led to the production of a
strongly fluorescent strain, Act-4, that displayed biocontrol traits typical of
P. flocculosa WT. Following inundative applications, growth of P. flocculosa Act
4 was closely and almost exclusively associated with the colonies of the pathogen
regardless of the powdery mildew species or the host plant tested. Development of
P. flocculosa Act-4 on control leaves alone was extremely limited 24 h after its
application and was typical of the epiphytic growth characterizing this type of
yeast-like fungus. Based on the strong correlation between the colonization
pattern of the different powdery mildew species tested and the presence of P.
flocculosa Act-4, as determined by its fluorescence, it seems that growth of the
BCA is dependant on the presence of powdery mildews. These results demonstrate
that the GFP technology can be used to study plant-pathogen-BCA interactions and
fulfill a wide array of purposes ranging from fundamental observations of the
biocontrol behavior of a BCA to very applied ones serving some of the
requirements for the registration of BCA's such as defining their environmental
fate.
PMID- 17028025
TI - Basal cortisol and DHEA levels in women with borderline personality disorder.
AB - Previous research suggests that in borderline personality disorder (BPD) normal
stress regulation, with a main role for cortisol, is disturbed. However, most
studies were confounded by their lack of attention to co-morbidity. Relevant
patient characteristics such as depression, childhood abuse, posttraumatic stress
disorder (PTSD) and copying styles were not systematically examined. Moreover,
none of the studies incorporated dehydroepiandrosterone (DHEA), a hormone that
can antagonize the effects of cortisol. Hence, the present pilot study
investigates the basic levels of cortisol and DHEA and the ratio (CDR) between
the two hormones in BPD patients. Twenty-two women with BPD and 22 healthy female
controls provided two diurnal (8 a.m./8 p.m.) salivary samples. Overall cortisol
levels were not significantly increased in the patient group as a whole but only
in those patients diagnosed with co-morbid PTSD and a history of childhood abuse.
The patients' cortisol secretions decreased relatively less steep during the day
than it did in the controls. Surprisingly, morning DHEA levels were significantly
higher in the patients than in the controls. Moreover, the CDR showed a
significantly larger and less favourable increase in the BPD group during the
day. In the patients lower levels of DHEA in the evening proved significantly
related to a stronger tendency to avoid active problem solving and a lowered
inclination to seek social support. The current findings underline the relevance
of cortisol and DHEA assessments and the need for further scrutiny of their
interplay to foster our understanding of the biological basis of stress
regulation in BPD.
PMID- 17028026
TI - Comparing safety climate factors as predictors of work-related driving behavior.
AB - INTRODUCTION: Research suggests safety climate (SC) is a strong predictor of
safety-related outcomes in organizations. This study explores the relationship
between six SC dimensions and four aspects of work-related driving. METHOD: The
SC factors measured were "communication and procedures," "work pressures,"
"relationships," "safety rules," "driver training," and "management commitment."
The aspects of self-reported occupational driving measured were traffic
violations, driver error, driving while distracted, and pre-trip vehicle
maintenance. RESULTS: Hierarchical regression analyses revealed that the SC
factors accounted for significant amounts of variance in all four aspects of work
related driving, over and above the control factors of age, sex, and work-related
driving exposure. However, further investigation indicated certain SC factors
(particularly safety rules, communication, and management commitment) were more
strongly related to specific aspects of work-related driving behavior than
others. Together, the SC factors were better able to predict self-reported
distraction from the road than the other aspects of driving behavior measured.
Implications for occupational safety, particularly for the management of work
related drivers are discussed.
PMID- 17028027
TI - Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin
variant tetramers in serum against dissociation required for amyloidogenesis.
AB - Transthyretin (TTR) tetramer dissociation, misfolding and misassembly are
required for the process of amyloid fibril formation associated with familial
amyloid polyneuropathy (FAP). Preferential stabilization of the native TTR
tetramer over the dissociative transition state by small molecule binding raises
the kinetic barrier of tetramer dissociation, preventing amyloidogenesis. Two
NSAIDs, diflunisal and flufenamic acid, and trivalent chromium have this ability.
Here, we investigated the feasibility of using these molecules for the treatment
of FAP utilizing serum samples from 37 FAP patients with 10 different mutations.
We demonstrated that the TTR heterotetramer structures in FAP patients serum are
significantly less stable than that in normal subjects, indicating the
instability of the variant TTR structure is a fundamental cause of TTR
amyloidosis. We also demonstrated that therapeutic serum concentrations of
diflunisal (100-200 microM) stabilized serum variant TTR tetramer better than
those of flufenamic acid (35-70 microM). Trivalent chromium at levels obtained by
oral supplementation did not stabilize TTR in a statistically significant
fashion. Importantly, diflunisal increased serum TTR stability in FAP patients
beyond the level of normal controls.
PMID- 17028029
TI - Voltage-gated potassium channel antibodies associated limbic encephalitis in a
patient with invasive thymoma.
AB - Recently, limbic encephalitis (LE) associated with Voltage-gated potassium
channel antibody (VGKC-Ab) has been postulated as a new autoimmune disorder. Most
previously reported cases of VGKC-Ab-associated LE were non-paraneoplastic, and
reports of a paraneoplastic type are rare. Here we describe a 59-year-old woman
with paraneoplastic VGKC-Ab-associated LE preceding the recurrence of invasive
thymoma. There was a close temporal relationship between the clinical course and
the changes of the VGKC-Ab titer. Unlike many of the non-paraneoplastic VGKC-Ab
associated LE cases, our cases showed the more extensive high intensity lesions
on MRI and the absence of seizure and hyponatremia.
PMID- 17028028
TI - Chronic high-dose haloperidol has qualitatively similar effects to risperidone
and clozapine on immediate-early gene and tyrosine hydroxylase expression in the
rat locus coeruleus but not medial prefrontal cortex.
AB - Acute administration of clozapine has been reported to activate the locus
coeruleus (LC) and beta-adrenoceptor-dependent Fos immunoreactivity in the medial
prefrontal cortex (mPFC) in rodents. Haloperidol is reported to exhibit a similar
acute effect on LC firing and beta-adrenoceptor dependent Fos immunoreactivity in
the mPFC but only at high doses. We compared the effects of chronic 4-week
treatment with risperidone (1mg/kg/day s.c.), clozapine (10mg/kg/day s.c.) or a
high dose of haloperidol (4mg/kg/day s.c.) on immediate-early gene protein (c
Fos, Egr-1 and Egr-2) and tyrosine hydroxylase (TH) expression. In the mPFC,
haloperidol decreased, whereas clozapine increased, c-Fos immunoreactivity. Only
haloperidol increased Egr-1 immunoreactivity. There was no significant effect on
Egr-2 immunoreactivity. In the LC, both Egr-1 and Egr-2 expression was down
regulated by all three antipsychotics. Clozapine and risperidone increased TH
immunoreactivity in both mPFC and LC. Haloperidol caused a smaller increase in TH
expression in the LC, but did not alter expression in the mPFC. In conclusion,
despite qualitatively similar effects in the LC, chronic treatment with
haloperidol had different effects to clozapine and risperidone in the mPFC. This
may relate to the reported advantage of clozapine and risperidone over
haloperidol against prefrontal cortical-dependent cognitive and negative
symptoms.
PMID- 17028031
TI - Yeast cell inactivation related to local heating induced by low-intensity
electric fields with long-duration pulses.
AB - The effects of electric field (EF) treatments on Saccharomyces cerevisiae
viability were investigated using a PG200 electroporator (Hoefer Scientific
Instrument, San Fransisco, CA, USA) with specific attention to induced thermal
effects on cell death. Lethal electric fields (1.5 kV cm(-1) for 5 s) were shown
to cause heat variations in the cell suspension medium (water+glycerol), while
corresponding classical thermal treatments at equivalent temperatures had no
effect on the cells viability. Variations of the electrical conductivity of the
intra- and extracellular matrix caused by ions and solutes transfer across the
membrane were shown to be involved in the observed heating. The results permitted
to build a theoretical model for the temperature variations induced by electric
fields. Using this model and the electrical conductivity of the different media,
a plausible explanation of the cell death induced by low-intensity electric
fields with long-duration pulses has been proposed. Indeed, cell mortality could
in part be caused by direct and indirect effects of electric fields. Direct
effects are related to well known electromechanical phenomena, whereas indirect
effects are related to secondary thermal stress caused by plasma membrane
thermoporation. This thermoporation was attributed to electrical conductivity
variations and the corresponding intracellular heating.
PMID- 17028030
TI - Occurrence of nervous system involvement in SIRS.
AB - Systemic inflammatory response syndrome (SIRS) is a medical condition in which
the all-organ microcirculation is affected including nervous system. We describe
neurological findings in 64 patients with SIRS at Hospital das Clinicas of Sao
Paulo University School of Medicine; 45.3% were male and 54.7% female; their age
ranged from 16 to 95 years old. SIRS was caused by infection in 68.8% of
patients, trauma in 10.9%, burns in 7.8%, and elective surgery in 4.7%. The
central nervous system involvement occurred in 56.3% of patients and was
characterized as encephalopathy in 75%, seizures in 13.9%, non-epileptic
myoclonus in 2.8%, and ischemic stroke in 8.3%. The magnetic resonance imaging,
cerebrospinal fluid and electroencephalographic changes were unremarkable in
encephalopathic patients. Neuromuscular disorders were diagnosed in 43.7%.
Critical ill polyneuropathy was characterized in 57.1%, critical ill myopathy in
32.1%, demyelinating neuropathy in 7.2%, and pure motor neuropathy in 3.6%. Nerve
and muscle pathological studies dismissed inflammatory abnormalities. The
identification of these conditions has important economic implications and may
change the critically ill patients' prognosis.
PMID- 17028032
TI - On the lag phase and initial decline of microbial growth curves.
AB - The lag phase is generally thought to be a period during which the cells adjust
to a new environment before the onset of exponential growth. Characterizing the
lag phase in microbial growth curves has importance in food sciences,
environmental sciences, bioremediation and in understanding basic cellular
processes. The goal of this work is to extend the analysis of cell growth curves
and to better estimate the duration of the lag phase. A non-autonomous model is
presented that includes actively duplicating cells and two subclasses of non
duplicating cells. The growth curves depend on the growth and death rate of these
three subpopulations and on the initial proportion of each. A deterministic and a
stochastic model are both developed and give the same results. A notable feature
of the model is the decline of cells during the early stage of the growth curve,
and the range of parameters when this decline occurs is identified. A limited
growth model is also presented that accounts for the lag, exponential growth and
stationary phase of microbial growth curves.
PMID- 17028033
TI - Orientational control is an efficient control mechanism for phase switching in
the E. coli fim system.
AB - The fim system in E. coli controls the expression of type-1 fimbriae. These are
hair-like structures that can be used to attach to host cells. Fimbriation is
controlled by a mechanism called "orientational control." We present two families
of models for orientational control to understand the details of how it works. We
find that the main benefits of orientational control are that (i) it allows rapid
adjustment of fimbriation levels in response to a change of environmental
conditions while (ii) keeping the overall frequencies with which a cell switches
between the fimbriate state and the afimbriate state low. The main reason for the
efficiency of orientational control in regulation of fimbriation levels is that
it keeps the system far from its steady state.
PMID- 17028034
TI - Probing the role of microenvironment for microencapsulated Sacchromyces
cerevisiae under osmotic stress.
AB - Cell encapsulation opens a new avenue to the oral delivery of genetically
engineered microorganism for therapeutic purpose. Osmotic stress is one of the
universal chemical stress factors in the application of microencapsulation
technology. In order to understand the effect and mechanism of the encapsulated
microenvironment on protecting cells from hyper-osmotic stress, yeast cells of
Saccharomyces cerevisiae Y800 were encapsulated in calcium alginate micro-gel
beads (MB), alginate-chitosan-alginate (ACA) solid core microcapsules (SCM), and
ACA liquid core microcapsules (LCM), respectively. The stress-induced
intracellular components and enzyme activity including trehalose, glycerol and
super oxide dismutase (SOD) were measured. Free cell culture was used as control.
The survival of encapsulated cells and the cells released from MB, SCM and LCM
after osmotic shock induced by NaCl solution (1, 2 and 3M) was evaluated. An
analysis method was established to probe the effect of encapsulated
microenvironment on the cell tolerance to osmotic stress. The results showed that
LCM gave rise to the highest level of intracellular trehalose and glycerol, and
SOD activity, as well as the highest survival rate of encapsulated cells or cells
released from microcapsule. It was demonstrated that LCM was able to induce the
highest stress response and stress tolerance of cells, which was adapted during
culture, while SCM failed. The theoretical analysis revealed that it was the
liquid alginate matrix in microcapsule that played a central role in
domesticating the cells to adapt to hyper-osmotic stress. This finding provides a
very useful guideline to cell encapsulation.
PMID- 17028035
TI - Tumor necrosis factor alpha alters Na+-K+ ATPase activity in rat cardiac
myocytes: involvement of NF-kappaB, AP-1 and PGE2.
AB - There has been increasing evidence that tumor necrosis factor alpha (TNF-alpha)
is synthesized by cardiomyoctes and contributes to their impaired function and to
cardiac failure. Because the Na(+)-K(+) ATPase is a key player in the contraction
of cardiomyocytes, this work was undertaken to study the effect of TNF-alpha on
the Na(+)-K(+) ATPase in rat heart. Sprague Dawley rats (Rattus norvegicus) were
injected with TNF-alpha (270 ng/100 g body weight) and 4 h later the ventricles
were isolated, homogenized and assayed for their Na(+)-K(+) ATPase activity. The
effect of TNF-alpha on the pump was studied also in isolated myocytes treated in
suspension. The involvement of PGE2 was investigated by pre-treating animals or
cells with indomethacin, an inhibitor of COX enzymes. The involvement of NF
kappaB and AP-1 was studied using their respective inhibitors PDTC and curcumin.
A time response study showed an increase in the activity of the Na(+)-K(+) ATPase
in the left and right ventricles of animals treated with the cytokine, with no
change in its protein expression. This effect disappeared in the presence of
indomethacin suggesting an involvement of PGE(2) in the action of TNF-alpha. Rats
and cells treated directly with PGE(2) showed a dose-dependent response. A
decrease in the activity of the Na(+)-K(+) ATPase was observed at a low dose and
an increase at a high dose in both ventricles. Since PGE(2) is suspected to be
the active mediator in TNF-alpha signaling, inhibiting its synthesis by
inhibiting some suspected transcription factors was attempted. PDTC abrogated
fully, and curcumin partially the effect of the cytokine. It was concluded that
TNF-alpha activates NF-kappaB and AP-1 and induces PGE(2) release which alters
dose-dependently the activity of the pump by activating different EP receptors
with different affinities for PGE(2).
PMID- 17028036
TI - Cyclopamine treatment of human embryonic stem cells followed by culture in human
astrocyte medium promotes differentiation into nestin- and GFAP-expressing
astrocytic lineage.
AB - Human embryonic stem cells (hESCs) are able to differentiate into various cell
types, including neuronal cells and glial cells. However, little information is
available regarding astrocyte differentiation. This report describes the
differentiation of hESCs into nestin- and GFAP-expressing astrocytes following
treatment with cyclopamine, which is an inhibitor of Hedgehog (Hh) signaling, and
culturing in human astrocyte medium (HAM). In hESCs, cyclopamine treatment
suppressed the expression of Hh signaling molecules, the Hh signaling target
gene, and ESC-specific markers. Clyclopamine also induced the differentiation of
the cells at the edges of the hESC colonies, and these cells stained positively
for the early neural marker nestin. Subsequent culturing in HAM promoted the
expression of the astrocyte-specific marker GFAP, and these cells were also
nestin-positive. These findings indicate that treatment with cyclopamine followed
by culturing in HAM leads to the differentiation of hESCs into nestin- and GFAP
expressing astrocytic lineage.
PMID- 17028037
TI - Assessing the impact of nutrient enrichment in estuaries: susceptibility to
eutrophication.
AB - The main aim of this study was to develop a generic tool for assessing risks and
impacts of nutrient enrichment in estuaries. A simple model was developed to
predict the magnitude of primary production by phytoplankton in different
estuaries from nutrient input (total available nitrogen and/or phosphorus) and to
determine likely trophic status. In the model, primary production is strongly
influenced by water residence times and relative light regimes. The model
indicates that estuaries with low and moderate light levels are the least likely
to show a biological response to nutrient inputs. Estuaries with a good light
regime are likely to be sensitive to nutrient enrichment, and to show similar
responses, mediated only by site-specific geomorphological features. Nixon's
scale was used to describe the relative trophic status of estuaries, and to set
nutrient and chlorophyll thresholds for assessing trophic status. Estuaries
identified as being eutrophic may not show any signs of eutrophication.
Additional attributes need to be considered to assess negative impacts. Here,
likely detriment to the oxygen regime was considered, but is most applicable to
areas of restricted exchange. Factors which limit phytoplankton growth under high
nutrient conditions (water residence times and/or light availability) may favour
the growth of other primary producers, such as macrophytes, which may have a
negative impact on other biological communities. The assessment tool was
developed for estuaries in England and Wales, based on a simple 3-category
typology determined by geomorphology and relative light levels. Nixon's scale
needs to be validated for estuaries in England and Wales, once more data are
available on light levels and primary production.
PMID- 17028038
TI - Reversibly stable thiopolyplexes for intracellular delivery of genes.
AB - Novel polyaspartamide non-viral carriers for gene therapy were synthesized by
introducing, on the same polymer backbone, positively charged groups, for
electrostatic interactions with DNA, and thiol groups for the formation of
disulfide bridges between polymer chains. The introduction of thiols was aimed to
have a vector with low redox potential sensitivity: disulfide crosslinking in
fact, being stable in extracellular environment, allowed either to have stable
complexes in plasma, that can protect DNA from metabolism, or to be reduced
inside the cell, where the excess of glutathion in reduced form maintains a low
redox potential. The consequent destabilization of the complex after disulfide
cleavage can release DNA selectively inside the cells. Alpha,beta-poly(N-2
hydroxyethyl)-D,L-aspartamide (PHEA) was used as starting polymer being a highly
water-soluble synthetic polymer, already proposed with success as therapeutic
carrier by our group. In this study, PHEA was firstly functionalised with
ethylendiamine, obtaining a well defined copolymer with pendant primary amine
groups (PHEA-EDA), to which N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP)
and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTA) were linked in two
subsequent steps, allowing the introduction of thiol and cationic groups
respectively. Finally DTT treatment lead to the final PHEA-EDA-SH-CPTA
thiopolycation, named PESC. The present work describes the synthesis and
characterization of the thiopolycation PESC. 1H NMR spectroscopy detected the
derivatization molar degrees in SPDP and CPTA; the formation of DNA complexes
(thiopolyplexes), their stability in the presence of polyanions and the ability
to release DNA under reductive conditions were studied by agarose gel
electrophoresis. DNase II degradation study was carried out to detect the ability
of thiopolyplex to stabilize DNA towards enzymatic metabolism. Thiopolyplexes
were then characterized by Dynamic Light Scattering (DLS) and Zeta Potential
analysis. Finally, in vitro toxicity profile (MTT) and gene transfer efficiency
(Luciferase assay) were carried out to evaluate thiopolyplex biocompatibility,
safety and efficacy to be used as gene delivery system.
PMID- 17028039
TI - Protective effects of transcription factor HESR1 on retinal vasculature.
AB - HESR1 is a basic helix-loop-helix transcription factors regulated by the Notch
signaling pathway in vertebrate and Drosophila embryos, and is related to the
HES/Hairy/E (sp1) family. HESR1 is a downstream target of Notch in endothelial
cells and could be an effector of Notch signaling in these cells. HESR1 is
necessary for the induction of a tubular network and for continued maintenance of
mature and quiescent blood vessels. To examine the role of HESR1 in retinal
neovascularization, we transfected retinal vascular endothelial cells (HRCECs)
with the HESR1 gene and studied its effects on the expression of angiogenic
factors, on the proliferation and migration of endothelial cells, and on the
formation of tube-like structures (TLSs). Overexpression of HESR1 downregulated
VEGFR-2 expression, upregulated occludin expression, inhibited the migration and
proliferation of HRCECs, and inhibited the formation of TLSs. Thus, HESR1 plays a
key role in the finely tuned network of molecules involved in the regulation of
retinal vascular homeostasis. HESR1 seems to inhibit the vessel-promoting effects
of VEGF, shift endothelial cells from a proliferative state to a quiescent state,
and restore normal vessel structures. Expression of the HESR1 gene in retinal
vascular endothelial cells may protect retinal blood vessels and may be useful in
the treatment of diseases involving damage to the retinal vasculature, including
diabetic retinopathy, age-related macular degeneration, and retinal vein
occlusion.
PMID- 17028040
TI - Effects of big endothelin-1 in comparison with endothelin-1 on the microvascular
blood flow velocity and diameter of rat mesentery in vivo.
AB - Synthetic big endothelin-1 (ET-1), a 39-residue precursor of ET-1, has been
reported to elicit potent contractile action on helical strip specimens obtained
from the porcine coronary artery, but its molar potency was found to be 140-fold
lower than that of ET-1 [Saito, Y., Nakao, K., Mukoyama, M., Imura, H., 1990.
Increased plasma endothelin level in patients with essential hypertension. N.
Engl. J. Med. 322, 205]. It has been hypothesized that the increased rate of
production and/or release of ET-1 from the vascular endothelium may contribute to
the pathogenesis of hypertension. However, the effects of big ET-1 in comparison
with ET-1 on the macrocirculation and microcirculation of the rat mesentery have
not been well documented. Thus, our main purpose for this study was to examine
the effects of both big ET-1 and ET-1 to clarify the role of phosphoramidon in
inhibiting the conversion of big ET-1 to ET-1, by investigating the systemic
blood pressure, microvascular blood flow velocity, and diameters of arterioles
and venules of the rat mesentery. For this purpose, two groups of experiments
were performed. In these experiments, the mesentery was arranged for in situ
intravital microscopic observation under transillumination. In the first group of
experiments, intravenous cumulative injections of big ET-1 or ET-1 were infused
through a catheter inserted into the right jugular vein. Infusion of big ET-1 (1
8 nmol/kg) elicited a long-lasting significant pressor effect. Infusion of big ET
1 (1-2 nmol/kg) elicited a significant dose-dependent increase in the
microvascular blood flow velocity both in arterioles (20-30 microm) and venules
(30-40 microm). Microvascular diameters exhibited a slight but significant
vasodilator effect. However, the infusion of big ET-1 (4-8 nmol/kg) elicited a
dose-dependent significant decrease in the blood flow velocities, and diameters
returned to control measurements. The administration of ET-1 (0.25-2 nmol/kg)
induced a dose-dependent significant decrease in the blood flow velocity of
arterioles and venules, and their diameters exhibited a vasoconstrictive effect
more prominent in arterioles than in venules. In the second group of experiments,
cumulative injections of phosphoramidon (30 mg/kg/10 min) were administered 10
min prior to the infusion of big ET-1. Phosphoramidon significantly suppressed
the long-lasting significant pressor effect and significantly inhibited the dose
dependent increase and dose-dependent decrease in the microvascular blood flow
velocity produced by big ET-1 in the rat mesenteric microcirculation. This study
observed differences in the effects big ET-1 and ET-1 have on the rat mesenteric
microcirculation and proposes a possible mechanism explaining these differences.
Moreover, phosphoramidon markedly inhibited the conversion of big ET-1 to ET-1 in
the rat mesenteric microcirculation, which may suggest an inhibition of the
enzyme which converts big ET-1 to ET-1.
PMID- 17028041
TI - Ionizing radiation decreases capillary-like structure formation by endothelial
cells in vitro.
AB - For successful tissue engineering in surgical radiotherapy patients, irradiated
endothelial cells (EC) must form new blood vessels to nourish and build
connections with the engineered segment. Therefore, it is critical to understand
neovasculogenesis by irradiated EC. The objective of this study was to determine
the effects of ionizing radiation on endothelial cell proliferation and capillary
like structures (CLS) formation. Human Umbilical Vein Endothelial Cells (HUVEC)
were irradiated with single or fractionated doses of radiation. Proliferation was
determined by counting cells. CLS morphology was analyzed from photomicrographs.
A single dose of 8 Gy radiation was highly lethal to HUVEC compared to lower
dosage. A single dose had more of an inhibitory effect on cell proliferation
compared to the same dose delivered in a fractionated manner. CLS formation began
after cells reached confluency. To form a CLS, a single cell expanded, and a
number of cells rearranged around its periphery in an oval fashion (mimicking a
vessel wall). The central cell later disintegrated leaving a void, mimicking the
lumen. Irradiated EC can form CLS, although they are fewer and smaller compared
to those by sham cells. By disrupting the peripheral cells, >or=4 Gy doses
significantly reduced the number of CLS. The disruptive affect was seen more with
large CLS compared to small CLS. At different doses, the shapes of CLS were not
significantly different.
PMID- 17028042
TI - Price differences between Japan and the US for medical materials and how to
reduce them.
AB - INTRODUCTION: Previous reports (1996, 1997) have revealed that the market prices
of medical materials in Japan were two to four times higher than those in the US.
The Japanese government introduced the foreign price adjustment rule (FPA) in
2002 to reduce reimbursement prices in Japan. We aimed to investigate the current
price differences between Japan and the US in the first half of 2005 and to
evaluate the effectiveness of the FPA. METHODS: The investigation was performed
at two joint purchasing organizations (JPO) and a hospital group in the US, and
at a university hospital in Japan. Forty-one items in 14 categories were selected
in advance. RESULTS: The price ratio (Japanese price/US price) was largest at 4.5
6.8 for percutaneous transluminal coronary angioplasty (PTCA) balloon catheters
and 1.4-6.0 for vascular grafts. The price ratio was smallest at 1.2-2.4 for
automatic sutures, 1.4-1.6 for Swan-Ganz catheters, and 1.5-2.3 for mechanical
valves. DISCUSSION: The price differences between Japan and the United States
were found to have rather widened with the exception of the pacemaker, because
their market prices decreased more markedly in the United States. The
investigation suggests several problems with the FPA: (1) the determination
process of reimbursement prices is inappropriate, which has made the Japanese
market less competitive, (2) the FPA needs too much time for the resolution of
price differences, and (3) price data collected according to the FPA lacks
strictness. CONCLUSIONS: The high prices of medical material in Japan need to be
adjusted down with more appropriate measures such as the full cost or cost
inclusion methods.
PMID- 17028043
TI - Patient (customer) expectations in hospitals.
AB - The expectations of patient are one of the determining factors of healthcare
service. The purpose of this study is to measure the Patients' Expectations,
based on Patient's Rights. This study was done with Likert-Survey in Trabzon
population. The analyses showed that the level of the expectations of the patient
was high on the factor of receiving information and at an acceptable level on the
other factors. Statistical meaningfulness was determined between age, sex,
education, health insurance, and the income of the family and the expectations of
the patients (p<0.05). According to this study, the current legal regulations
have higher standards than the expectations of the patients. The reason that the
satisfaction of the patients high level is interpreted due to the fact that the
level of the expectation is low. It is suggested that the educational and public
awareness studies on the patients' rights must be done in order to increase the
expectations of the patients.
PMID- 17028044
TI - Genetic variance contributes to ingestive processes: a survey of eleven inbred
mouse strains for fat (Intralipid) intake.
AB - Genetic variation across inbred and outbred mouse strains have been observed for
intake of sweet solutions, salts, bitter tastants and a high-fat diet. Our
laboratory recently reported marked strain differences in the amounts and/or
percentages of kilocalories of sucrose consumed among 11 inbred and one outbred
mouse strains exposed to a wide range of nine sucrose concentrations (0.0001-5%)
in two-bottle 24-h preference tests. To assess whether differences in fat intake
were similarly associated with genetic variation, the present study examined
intake of chow, water and an emulsified fat source (Intralipid) across nine
different concentrations (0.00001-5%) in the same 11 inbred and 1 outbred mouse
strains using two-bottle 24-h preference tests, which controlled for Intralipid
concentration presentation effects, Intralipid and water bottle positions, and
measurement of kilocalorie intake consumed as Intralipid or chow. Strains
displayed differential increases in Intralipid intake relative to corresponding
water with significant effects observed at the seven (BALB/cJ: 0.001% threshold
sensitivity), four (AKR/J, C57BL/6J, DBA/2J, SWR/J: 0.5% threshold sensitivity),
three (CD-1, C57BL/10J, SJL/J: 1% threshold sensitivity) and two (A/J, CBA/J,
C3H/HeJ, 129P3/J: 2% threshold sensitivity) highest concentrations. In assessing
the percentage of kilocalories consumed as Intralipid, SWR/J mice consumed
significantly more at the three highest concentrations to a greater degree than
BALB/cJ, C57BL/6J, CD-1, C3H/HeJ, DBA/J and 129P3/J strains which in turn
consumed more than A/J, AKR/J, CBA/J, C57BL/10J and SJL/J mice. Relatively strong
(h2 = 0.73-0.79) heritability estimates were obtained for weight-adjusted
Intralipid intake at those concentrations (0.001-1%) that displayed the largest
strain-specific effects in sensitivity to Intralipid. The identification of
strains with diverging abilities to regulate kilocalorie intake when presented
with high Intralipid concentrations may lead to the successful mapping of genes
related to hedonics and obesity.
PMID- 17028045
TI - Differential effects of hypocretins on noise-alone versus potentiated startle
responses.
AB - Hypocretins are recently discovered neuropeptides, synthesized exclusively in the
hypothalamus with excitatory efferents to noradrenergic, serotonergic, and
GABAergic (gamma-aminobutyric acid) neurons. Hypocretins also increase
corticotropin releasing hormone (CRH) secretion. These actions suggest a possible
role for hypocretins in the neurobiology of anxiety, fear, or startle mechanisms.
We examined the effects of intracerebroventricular (ICV) administration of
hypocretin-A and hypocretin-B on behavior in the Startle Potentiated Startle
(SPS) paradigm, a repeated measures, non-shock animal model for studying the
classically conditioned enhancement of acoustic startle in the rat. SPS has been
used to study effects of anxiolytic treatments. Male Sprague-Dawley rats were
tested using the SPS paradigm for 3 days (M-W-F). Following training, rats were
anesthetized and 26 gauge stainless cannulae were permanently implanted into the
lateral ventricle for intracerebroventricular (ICV) infusions. Following 6-9 days
of recovery period, the M-W-F SPS testing was resumed. ICV infusion of both
Hypocretin-A (1 and 3 nM) and Hypocretin-B (3 and 10 nM) produced significant
reduction in Noise Alone Startle amplitude compared to pre-infusion baseline,
whereas infusion with vehicle did not affect Noise Alone Startle. The effect of
Hypocretin-B was brief (first 10 min post-infusion), whereas the effect of
Hypocretin-A persisted across much of the 50 min post-infusion period. Neither
Hypocretin-A nor Hypocretin-B significantly altered the magnitude of the SPS
response. Contrary to our expectations, hypocretins seems to possess anxiolytic
rather than pro-anxiogenic properties, as indicated by decrease in Noise Alone
Startle.
PMID- 17028046
TI - The effect of monosodium glutamate on parotid salivary flow in comparison to the
response to representatives of the other four basic tastes.
AB - Parotid salivary flow was recorded from eight fit and healthy subjects using
modified Lashley cups connected to an instantaneous flow meter in response to
gustatory stimuli. The gustatory stimuli were monosodium glutamate (MSG), sodium
chloride, sucrose, magnesium sulphate and citric acid. Stimuli were applied for
30 s, and repeated after the flows had returned to baseline following the rinse.
Subjects were a significant source of variation for salivary response to each
different test stimuli (p<0.001). The normalised salivary flow showed a strong
correlation to concentration for all test stimuli (p<0.0001). The parotid
salivary flow to MSG (umami) showed a dose-dependant response in which both Na(+)
and glutamate ions contributed. The overall order of relative salivary flow
responses from highest to lowest flows was citric acid (sour)>MSG (umami)>NaCl
(salt)>sucrose (sweet)>=magnesium sulphate (bitter). The relative responses of
the peak salivary flows showed the same ordered relation. The peak salivary flow
provided a greater contribution to the response to citric acid, NaCl and MSG
compared to the response to sucrose and magnesium sulphate.
PMID- 17028047
TI - Control of Schistosoma mekongi in Cambodia: results of eight years of control
activities in the two endemic provinces.
AB - In Cambodia, schistosomiasis is transmitted in the provinces of Kratie and Stung
Treng where approximately 80000 individuals are estimated to be at risk of
infection. The baseline prevalence of infection was estimated to be between 73%
and 88%, and cases of severe morbidity (hepatosplenomegaly, puberty retardation)
and mortality were very common. In 1994, the Ministry of Health of Cambodia
started schistosomiasis control applying universal chemotherapy with praziquantel
(40mg/kg). The coverage of the programme was between 62% and 86% for 8 years.
This simple control measure resulted in the control of the disease: no cases were
reported in 2004 and only three cases were reported in 2005. In addition, there
are no longer reports of cases of severe morbidity due to schistosomiasis. Since
the beginning of the control programme, a single dose of mebendazole (500mg) has
been combined with praziquantel during the mass chemotherapy; as a result the
prevalence of Ascaris lumbricoides and hookworms dropped from 74.5% to 10% and
from 86% to 40% respectively. The experience in Cambodia demonstrates that, with
political commitment, control of parasitic diseases is achievable even in a
situation of minimal resources. The programme represents a successful model for
other developing countries.
PMID- 17028048
TI - Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to
chloroquine and sulfadoxine-pyrimethamine in southern Papua, Indonesia.
AB - To determine the level of antimalarial drug resistance in southern Papua,
Indonesia, we assessed the therapeutic efficacy of chloroquine plus sulfadoxine
pyrimethamine (CQ+SP) for Plasmodium falciparum infections as well as CQ
monotherapy for P. vivax infections. Patients with P. falciparum failing therapy
were re-treated with unsupervised quinine+/-doxycycline therapy and those with P.
vivax with either unsupervised quinine+/-doxycycline or amodiaquine. In total,
143 patients were enrolled in the study (103 treated with CQ+SP and 40 with CQ).
Early treatment failures occurred in four patients (4%) with P. falciparum and
six patients (15%) with P. vivax. The failure rate by Day 28 for P. vivax was 65%
(95% CI 49-81). After PCR correction for re-infections, the Day 42 recrudescence
rate for P. falciparum infections was 48% (95% CI 31-65). Re-treatment with
unsupervised quinine+/-doxycycline resulted in further recurrence of malaria in
48% (95% CI 31-65) of P. falciparum infections and 70% (95% CI 37-100) of P.
vivax infections. Eleven patients with recurrent P. vivax were re-treated with
amodiaquine; there were no early or late treatment failures. In southern Papua, a
high prevalence of drug resistance of P. falciparum and P. vivax exists both to
first- and second-line therapies. Preliminary data indicate that amodiaquine
retains superior efficacy compared with CQ for CQ-resistant P. vivax.
PMID- 17028049
TI - Type 2 11beta-hydroxysteroid dehydrogenase activity in human ovarian cancer.
AB - In the ovary cortisol-cortisone inter-conversion is catalyzed by the enzyme
11beta-hydroxysteroid dehydrogenase (11beta-HSD). Its role in carcinomas of human
ovary is unknown. The majority of ovarian cancers are derived from ovarian
surface epithelium and the inflammation caused by successive ovulation seems to a
play a role in the development of cancer. Cortisol is known to act as anti
inflammatory agent and its metabolism by type 1 and type 11beta-HSD may control
the inflammatory action by cortisol in ovary. We undertook this study to
investigate type 2 11beta-HSD activity which functions exclusively oxidative
direction, in normal ovarian tissue compared to ovarian epithelial cancer.
Ovarian tissue was obtained from patients undergoing hysterectomy for both benign
and malignant disease. Tissue was placed immediately on dry ice and subsequently
transferred to a freezer where they were maintained at -70 degrees C. NAD
dependent 11beta-HSD activity was then determined in this tissue. T-test was
performed to determine statistical significance. Mean type 2 enzyme activity was
0.87 +/- 1.65 pmol/min g tissue in normal ovarian tissue versus a mean enzyme
activity of 2.96 +/- 1.37 pmol/mim g tissue in from cancer specimens. This
difference was statistically significant with a p-value of 0.03. Type 2 1beta-HSD
activity in ovarian cancer specimens was significantly higher than enzyme
activity measured in normal post-menopausal ovarian tissue. Decreased cortisol
levels due type 2 1beta-HSD activity may play a role neoplastic transformation as
well as tumor proliferation in ovarian cancer by eliminating anti-inflammatory
action of cortisol.
PMID- 17028050
TI - Mean curvature versus normality: a comparison of two approximations of Fisher's
geometrical model.
AB - Fisher's geometrical model amounts to a description of mutation and selection for
individuals characterised by a number of quantitative traits. In the present work
the fitness landscape is not assumed to be spherically symmetric, hence different
points, i.e. phenotypes, on a surface of constant fitness generally have
different curvatures. We investigate two different approximations of Fisher's
geometrical model that have appeared in the literature. One approximation uses
the average curvature of the fitness surface at the parental phenotype. The other
approach is based on a normal approximation of a distribution associated with new
mutations. Analytical results and simulations are used to compare the accuracy of
the two approximations.
PMID- 17028051
TI - Surnames in Western Europe: a comparison of the subcontinental populations
through isonymy.
AB - We studied the isonymic structure of Western Europe using the distributions of
26.2 million surnames in 8 countries, 125 regions and 2094 towns of the
Subcontinent. We found that, for the whole of Western Europe, Nei's distance was
correlated with geographic distance (r=0.610+/-0.009). It was observed that at
long geographic distances the isonymyc distance stays below linearity and tends
to become asymptotic, and this was attributed to long distance migration. A
dendrogram of the125 regions was built and the clusters identified by the
dendrogram are almost exactly coincident with the nations of the Subcontinent.
Random inbreeding calculated from isonymy, F(ST), was highest in Spanish regions,
and lowest in France. The geographical distribution of alpha in 2094 towns, high
in the Center and East of the Subcontinent and lower in Spain, is compatible with
the settlement of subsequent waves of migrants moving from the West and from the
South toward the centre of the Continent. The present surname structure of
Western Europe is strictly linked to local languages.
PMID- 17028052
TI - A proper schedule of weekly paclitaxel and gemcitabine combination is highly
active and very well tolerated in NSCLC patients.
AB - BACKGROUND: In a previous phase I dose-escalation study, we showed a weekly
administration of paclitaxel (TAX) and gemcitabine (GEM) to be active and very
well tolerated in non-small-cell lung cancer (NSCLC) patients, with the lack of
interaction between drugs. The dose of GEM 1500 mg/m(2) and TAX 100 mg/m(2) was
selected for phase II studies due to its predictable kinetic behaviour and less
severe thrombocytopenia. PATIENTS AND METHODS: Fifty-four chemo-naive patients
with advanced NSCLC (53 patients: stage IV) received TAX (100mg/m(2) i.v.
infusion over 1h) followed by GEM 1500 mg/m(2) over 30 min) on days 1, 8, 15 and
21 of a 28-day cycle. RESULTS: The objective response rate was 46% (95% CI 32
61), median OS of 10.4 ms (95% CI 6.5-4.3), and a 1-year survival rate of 53%.
Grades 3 and 4 haematological toxicity consisted of non-febrile neutropenia and
thrombocytopenia in 13 and 4% of the cycles, respectively. Grade 3 non
haematological toxicities were observed in three patients (asthenia, diarrhoea
and neuropathy), and were always reversible. CONCLUSIONS: This weekly schedule of
TAX and GEM is highly active in chemo-naive NSCLC patients and confirms the low
toxicity profile already observed in a previous phase I study.
PMID- 17028053
TI - Recognition of external object features in gas media using ultrasound
transmission tomography.
AB - The paper presents and analyzes a new way of recognizing external object features
(shape, size, location) in gas media using ultrasound transmission tomography
(UTT) with parallel-ray-projection scanning geometry. The concept of UTT in a gas
medium is close to classical tomography, however because of the nature of the
measurement environment, visualizing the internal structure of solid objects is
difficult; whereas it is possible to image their external features: their shape,
size and spatial location. The paper presents the results of examining the shape,
size and location of different objects in the air in the form of tomographic
images, obtained in parallel-ray-projection geometry, using a specially
elaborated research setup for UTT. Applying parallel-ray-projection geometry
enabled us to investigate the influence of scanning resolution on image quality.
In order to test the operation of the elaborated algorithm of tomographic image
reconstruction on the basis of correct measurement data, special software was
written for simulating the binary matrix of the measurements for a set of a dozen
or so solid objects of different shapes and a few simulations were performed.
PMID- 17028054
TI - Merging theory and mechanism in studies of gynodioecy.
AB - In gynodioecious species, females and hermaphrodites coexist and the genetics of
sex determination is usually nuclear cytoplasmic. Maintaining nuclear-cytoplasmic
gynodioecy requires polymorphism for the feminizing genes (contained in the
mitochondria) and the genes that restore male fertility (contained in the
nucleus). This complex polymorphism depends, in part, on there being negative
pleiotropic effects (i.e. costs) of the nuclear restorer alleles. Here, we
combine information from theoretical studies and studies on the molecular action
of restorer alleles in crops to interpret the probable costs of such alleles, and
suggest how various aspects of the theoretical models could be tested. In doing
so, we highlight how crops can be used to address evolutionary questions about
the maintenance of nuclear-cytoplasmic gynodioecy.
PMID- 17028055
TI - The perils and prospects of using phytohaemagglutinin in evolutionary ecology.
AB - Several techniques are available for quantifying the vertebrate immune response,
information that is particularly useful for understanding the contribution of
immunity to the evolution of life-history strategies. The most widely used is the
phytohaemagglutinin (PHA) skin-swelling technique, which is usually regarded as
an index of acquired immunity. However, our understanding of the effects of PHA
in skin is poor, despite the fact that it has implications for what the test can
tell us about immune activity. As we discuss here, a recent study by Martin and
colleagues on the response to PHA at the cellular level in wild birds has
highlighted the relative extent to which PHA-induced swelling, as most commonly
applied, measures innate immunity versus acquired immunity.
PMID- 17028056
TI - Mating and immunity in invertebrates.
AB - Mating and immunity are intimately linked to fitness. In both vertebrates and
invertebrates, recent investigations into mate choice for immunity, tradeoffs
between reproduction and immunity, and the relationships between post-mating
processes and immune function have revealed that mating and immunity are also
intimately linked to each other. Here, we focus on invertebrates and critically
examine the evidence that immunity is under sexual selection, both pre- and post
mating, and explore other hypotheses linking mating and immunity. We find little
evidence for a consensus regarding which theories best account for the
accumulating empirical data. However, we suggest that progress can quickly be
made by exploiting the intrinsic strengths of invertebrate model systems.
PMID- 17028057
TI - Activation of non-canonical NF-kappaB pathway mediated by STP-A11, an oncoprotein
of Herpesvirus saimiri.
AB - Although Saimiri Transforming Protein (STP)-A11, an oncoprotein of Herpesvirus
saimiri, has been known to activate NF-kappaB signaling pathway, the detailed
mechanism has not been reported yet. We herein report that STP-A11 activates non
canonical NF-kappaB pathway, resulting in p100 processing to p52. In addition,
translocation of p52 protein (NF-kappaB2) into the nucleus is observed by the
expression of STP-A11. STP-A11-mediated processing of p100 to p52 protein
requires proteosome-mediated proteolysis because MG132 treatment clearly blocked
p52 production in spite of the expression of STP-A11. Analysis of STP-A11 mutants
to activate NF-kappaB2 pathway discloses the requirement of TRAF6-binding site
not Src-binding site for STP-A11-mediated NF-kappaB2 pathway. Blockage of STP-A11
mediated p52 production using siRNA against p52 enhanced a chemotherapeutic drug
mediated cell death, suggesting that p52 production induced by the expression of
STP-A11 would contribute to cellular transformation, which results from a
resistance to cell death.
PMID- 17028058
TI - Efficacy of inactivated vaccines against H5N1 avian influenza infection in ducks.
AB - The current Asian H5N1 highly pathogenic avian influenza virus has spread over
much of Asia and into Europe and Africa. As well as affecting village and
commercial chicken operations in many South East Asian countries, it differs from
past H5 avian influenza viruses in that it causes morbidity and mortalities in
other domesticated birds, such as ducks and turkeys and in wild water birds.
Effective vaccines that can prevent infection, as well as disease, and be used in
a variety of avian species are needed for field use. In this report, a bivalent
H5N9+H7N1 oil emulsion vaccine is compared, in ducks, to a monovalent H5N3 oil
emulsion vaccine that has been derived by reverse genetics with an H5 from
A/chicken/Vietnam/C58/04. While both vaccines protected against morbidity, the
monovalent vaccine provided effective protection, with no evidence of shedding of
the challenge virus and no serological response to the H5N1 challenge virus.
PMID- 17028059
TI - Marek's disease virus up-regulates major histocompatibility complex class II cell
surface expression in infected cells.
AB - Many herpesviruses modulate major histocompatibility complex (MHC) expression on
the cell surface as an immune evasion mechanism. We report here that Marek's
disease virus (MDV), a lymphotrophic avian alphaherpesvirus, up-regulates MHC
class II cell surface expression in infected cells, contrary to all other
herpesviruses examined to date. This MDV-induced class II up-regulation was
detected both in vitro and in vivo. This effect was not solely an indirect effect
of interferon, which is a highly potent natural inducer of MHC class II
expression, since MHC class II up-regulation in cultured primary fibroblast cells
was confined to the infected cells only. MHC class II up-regulation was also
observed in infected cells of the bursa of Fabricius during the lytic phase of
MDV infection in birds and upon reactivation of MDV from latency in an MDV
transformed cell line. As MDV is a strictly cell-associated virus and requires
activated T cells for its life cycle, this up-regulation of MHC class II in
infected cells may contribute to virus spread within the infected host by
increasing the chance of contact between productively infected cells and
susceptible activated T cells.
PMID- 17028060
TI - Injection of the sciatic nerve with TMEV: a new model for peripheral nerve
demyelination.
AB - Demyelination of the human peripheral nervous system (PNS) can be caused by
diverse mechanisms including viral infection. Despite association of several
viruses with the development of peripheral demyelination, animal models of the
condition have been limited to disease that is either autoimmune or genetic in
origin. We describe here a model of PNS demyelination based on direct injection
of sciatic nerves of mice with the cardiovirus, Theiler's murine
encephalomyelitis virus (TMEV). Sciatic nerves of FVB mice develop inflammatory
cell infiltration following TMEV injection. Schwann cells and macrophages are
infected with TMEV. Viral replication is observed initially in the sciatic nerves
and subsequently the spinal cord. Sciatic nerves are demyelinated by day 5 post
inoculation (p.i.). Injecting sciatic nerves of scid mice resulted in increased
levels of virus recovered from the sciatic nerve and spinal cord relative to FVB
mice. Demyelination also occurred in scid mice and by 12 days p.i., hindlimbs
were paralyzed. This new model of virus-induced peripheral demyelination may be
used to dissect processes involved in protection of the PNS from viral insult and
to study the early phases of lesion development.
PMID- 17028061
TI - Synthesis and characterization of novel biotinylated carboxyl-terminal
parathyroid hormone peptides that specifically crosslink to the CPTH-receptor.
AB - Parathyroid hormone (PTH) regulates calcium, phosphorous and skeletal homeostasis
via interaction with the G protein-coupled PTH/PTHrP receptor, which is fully
activated by the amino-terminal 34 amino-acid portion of the hormone. Recent
evidence points to the existence of another class of receptors for PTH that
recognize the carboxyl (C)-terminal region of intact PTH (1-84) (CPTHRs) and are
highly expressed by osteocytes. Here we report the synthesis and characterization
of two novel bifunctional CPTH ligands that include benzoylphenylalanine (Bpa)
substitutions near their amino-termini and carboxyl-terminal biotin moieties, as
well as a tyrosine(34) substitution to enable radioiodination. These peptides are
shown to bind to CPTHRs with affinity similar to that of PTH (1-84) and to be
specifically and covalently crosslinked to CPTHRs upon exposure to ultraviolet
light. Crosslinking to osteocytes or osteoblastic cells generates complexes of 80
and 220 kDa, of which the larger form represents an aggregate that can be
resolved into the 80 kDa. The crosslinked products can be further purified using
immunoaffinity and avidin-based affinity procedures. While the molecular
structure of the CPTHR(s) remains undefined, these bifunctional ligands represent
powerful new tools for use in isolating and characterizing CPTHR protein(s).
PMID- 17028062
TI - Effects of design flow and treatment level on construction and operation costs of
municipal wastewater treatment plants and their implications on policy making.
AB - Construction costs of 55 municipal wastewater treatment plants in Israel
(secondary, advanced secondary, and advanced treatment) were analysed in order to
derive cost functions expressing the effects of design flow and treatment level
on construction costs. Three equations were derived (statistically significant,
p<0.01), one for each treatment level. These indicate that economy of scale may
become weaker as treatment level rises. Analysis of the distribution of
construction costs revealed negative correlation (p<0.05) between the
proportional cost of civil engineering and design flow, positive correlation
(p<0.05) between the proportional cost of elecromechanical equipment and design
flow, and no correlation between the proportional cost of electricity and control
and design flow. Operation costs were found to be 20-70% more sensitive than
construction costs to treatment level. The share of operation costs as part of
the total annual costs was found to increase both with design flow and treatment
level, whereas the share of construction costs concurrently decreased. The
implication of the findings on policy, and consequently on treatment plants
performance is discussed in the last part of the paper.
PMID- 17028063
TI - Degradation of endocrine disrupting bisphenol A by 254 nm irradiation in
different water matrices and effect on yeast cells.
AB - The photodegradation of bisphenol A (BPA) in pure water, surface water and
wastewater effluents was studied. The effect of different hydrogen peroxide
concentrations on degradation was investigated. The rate of BPA photolysis in the
presence of hydrogen peroxide was lower in wastewater effluent than in purified
water. Phenol, 1,4-dihydroxylbenzene and 1,4-benzoquinone were identified by
means of HPLC as intermediate products of the photodegradation of bisphenol A. In
addition, the disappearance of the estrogenic activity of bisphenol A during
irradiation was shown by the YES test. Based upon the YES test results, there was
a strong decrease of estrogenic activity of parent compound after 120 min
irradiation in the presence of hydrogen peroxide.
PMID- 17028064
TI - UV light assisted decolorization of dark brown colored coffee effluent by photo
Fenton reaction.
AB - The photochemical decolorization of coffee effluent has been examined by photo
Fenton (UV/Fe2+/H2O2) process. Effects of UV light intensity, initial coffee
concentration, iron dose and H2O2 dose on the color removal of model coffee
effluent have been investigated. The rate of decolorization increased with
decreasing initial coffee effluent concentration. It was found that the Fe ion
dose and UV light intensity enhanced the decolorization rate. The decolorization
process of coffee effluent could be divided into three established phases. At the
beginning of the photo-Fenton process, the instantaneous and significant increase
in color of the solution was found (Phase-I). In the subsequent phase (Phase-II),
the decolorization rate was initially fast and subsequently decreased. In Phase
III, the rate was accelerated and then the complete decolorization of model
coffee effluent was achieved. In order to elucidate the mechanisms of coffee
effluent color removal process, the concentration changes in Fe3+ and Fe2+
besides H2O2 were measured during the course of the photo-Fenton process. The
rate-determining step in Phase-II was the photo-Fenton reaction or photoreduction
of Fe3+. On the other hand, the decolorization process in Phase-III was highly
affected by Fenton reaction or decomposition of H2O2 with Fe2+. About 93%
mineralization of 250 mg L(-1) model coffee effluent was achieved after 250 min.
A comparative study for TiO2, ZnO and photo-Fenton oxidation processes has been
also carried out and the photo-Fenton process was found to be the most effective
for color removal of coffee effluent.
PMID- 17028065
TI - Characterization of soluble organic matter of waste activated sludge before and
after thermal pretreatment.
AB - Microwave (MW) irradiation and conventional heating (CH) at 96 degrees C was
successful in disrupting the complex waste activated sludge (WAS) floc structure
and releasing extra- and intra-cellular biopolymers, such as protein and sugars
from activated sludge flocs into soluble phase along with solubilization of
particulate chemical oxygen demand (COD). Soluble CODs of CH and MW-irradiated
WAS were 361+/-45% and 143+/-34% higher and resulted in 475+/-3% and 211+/-2%
higher cumulative biogas productions (CBP) relative to the control at the end of
23 days of mesophilic anaerobic digestion, respectively. Ultrafiltration (UF) was
used to characterize the soluble molecular weight (Mw) distributions of control
(unpretreated), CH and MW-irradiated WAS. Depending on the Mw fraction, the range
of substrate volumetric utilization rate increases from anaerobic digesters was
between 94% and 84% for CH and 26-113% for MW compared to the control for the
first nine days of the digestion. Digesters treating high Mw (>300 kDa) materials
resulted in smaller biodegradation rate constants, k, indicating that
microorganisms require a longer time to utilize high Mw fractions which are most
likely cell wall fragments and exopolymers.
PMID- 17028066
TI - Synthesis, biological activity and molecular modelling of new trisubstituted 8
azaadenines with high affinity for A1 adenosine receptors.
AB - We describe here the synthesis and biological activity of new 8-azaadenines
bearing both a phenyl group on C(2) and a 9-benzyl group substituted in the ortho
position with a Cl or a F atom or a CF(3) group, to verify the synergistic effect
of a combination of these substitution patterns on binding with the A(1)
adenosine receptors. In position N(6) aliphatic and cycloaliphatic substituents
were chosen which had been shown to bind well with the A(1) receptors. Because of
the high lipophilicity of these kinds of molecules, we also introduced a
hydroxyalkyl substituent in the same position. The compounds obtained generally
showed a very good affinity and selectivity for A(1) receptors. Some of the
compounds showed K(i) in the nanomolar range, one even in the subnanomolar range
(0.6 M). Molecular docking calculations were performed in order to evaluate the
interaction energies between the bovine A(1) receptor model and the selected
ligands, and then to correlate these energies with biological activities of the
ligands as obtained from the experiments. Molecular docking analysis suggests
different binding modes towards A(1) receptors that are plausible for these
ligands.
PMID- 17028071
TI - Determinants of substrate specificity in KdcA, a thiamin diphosphate-dependent
decarboxylase.
AB - Thiamin diphosphate-dependent decarboxylases catalyze the non-oxidative
decarboxylation of 2-keto carboxylic acids. Although they display relatively low
sequence similarity, and broadly different range of substrates, these enzymes
show a common homotetrameric structure. Here we describe a kinetic
characterization of the substrate spectrum of a recently identified member of
this class, the branched chain 2-keto acid decarboxylase (KdcA) from Lactococcus
lactis. In order to understand the structural basis for KdcA substrate
recognition we developed a homology model of its structure. Ser286, Phe381,
Val461 and Met358 were identified as residues that appeared to shape the
substrate binding pocket. Subsequently, site-directed mutagenesis was carried out
on these residues with a view to converting KdcA into a pyruvate decarboxylase.
The results show that the mutations all lowered the Km value for pyruvate and
both the S286Y and F381W variants also had greatly increased values of k(cat)
with pyruvate as a substrate.
PMID- 17028072
TI - Nursing education: key issues for the 21st century.
AB - In this paper, I reflect on what can be learned by engaging in future thinking
within our discipline, and what implications the results of that thinking may
have for the development of nursing education. Recognizing the marvelous
diversity of perspective within our discipline with regard to what will and ought
to be our future mandate, it seems reasonable to search for some grounding in
what might ensure that we enter that future wisely. We all know that change is a
fundamental characteristic of all future projections, and yet that insight seems
a weak justification for failure to plan. Nurse educators hold a particular
obligation to ensure that they are preparing the professionals who will take that
future forward. Although we have always recognized that they must nurse for today
with an eye on tomorrow, it is inordinately difficult to come to some agreement
on how we can best bridge that gap within our educational programs and
strategies. Toward this end, I draw on lessons that can be drawn from our
professional history as a rich and vibrant context to propose some key issues for
that future theorizing.
PMID- 17028073
TI - Education leadership in the clinical health care setting: a framework for nursing
education development.
AB - This paper describes how a new framework for clinical nursing education was
introduced at Counties Manukau District Health Board (CMDHB), New Zealand. The
project was initiated in response to the significant legislative and post
registration nursing education changes within New Zealand. The journey of change
has been a significant undertaking, and has required clear management, strong
leadership, perseverance and understanding of the organisation's culture. The
approach taken to managing the change had four stages, and reflects various
change management models. The first stage, the identification process, identified
the impetus for change. Creating the vision is the second stage and identified
what the change would look like within the organisation. To ensure success and to
guide the process of change a realistic and sustainable vision was developed.
Implementing the vision was the third stage, and discusses the communication and
pilot phase of implementing the nursing education framework. Stage four,
embedding the vision, explores the process and experiences of changing an
education culture and embedding the vision into an organisation. The paper
concludes by discussing the importance of implementing robust, consistent,
strategic and collaborative processes--that reflect and evaluate best educational
nursing practice.
PMID- 17028074
TI - Ethically involving students in faculty research.
AB - Students in nursing education programs have a right to privacy as they engage in
their learning. At the same time, their faculty may be engaged in nursing
education research in order to facilitate student learning. These two goals may
conflict when faculty engage students as participants in nursing education
research while at the same time facilitating their learning. Faculty as
researchers with their students may encounter a conflict of interest in
collecting data for their research while providing learning experiences for the
same students. As a basic principle, students must be engaged as participants in
an ethical manner that respects their rights for privacy. In this article, we
explore the issues of faculty as researchers of their students and suggest
strategies for addressing these issues.
PMID- 17028075
TI - Is there a role for higher education in preparing nurses?
AB - Nurse education is now almost wholly situated within universities
internationally. However, issues such as the necessity of higher education for
what is seen as a practical occupation and the question of whether or not nursing
is a profession arise. Newman viewed universities as places where training was
given but character was also formed and self-awareness was developed through
exposure to a wide range of disciplines and this type of education has helped to
shape other professions. If nursing fulfills the criteria for a profession then
it requires nurses to be properly educated in higher education. Poor media images
of nursing, opposition from within and outside of the profession and poor funding
for research, especially in the UK, where most nurses still do not enter the
register with a degree, mean that the place of nursing in higher education
remains on the periphery. Nurses must be competent to practice and higher
education is not incompatible with the development of competent practitioners.
However, higher education should take competent practitioners to a higher level
whereby they become capable: able to respond appropriately in unfamiliar
situations and to unfamiliar events. This paper argues for the role of higher
education for nurses in terms of developing capability.
PMID- 17028076
TI - Education, philosophy and academic practice: nursing studies in the
posthistorical university.
AB - This paper is an amended and abridged version of a seminar given at the NET/NEP
1st Nurse Education International Conference in Vancouver, Canada. The topic of
the paper arose from our growing concerns about the state of nurse education and
its position in the university at the start of the twenty-first century. We share
the fears expressed by Readings that the university has lost its way and is
increasingly driven by a business agenda and a quest for ever-greater efficiency.
Our biggest concern is with the impact that the so-called 'posthistorical
university' is having on the study of nursing, particularly the growing pressure
on nurse academics to focus their attention and energy on output at the expense
of process, and on research at the expense of practice and practitioner
development. We suggest that the solution might lie with Jean-Francois Lyotard's
notion of postmodern philosophy as a way of opening up debate and, in his words,
saving the honour of thinking.
PMID- 17028077
TI - Evolution of anthropogenic aerosols in the coastal town of Salina Cruz, Mexico:
part II particulate phase chemistry.
AB - An analysis of atmospheric gases and particles during periods of land and sea
breezes in a coastal city in southwest Mexico indicates limited removal of total
particle mass by deposition during periods when the air resides over the ocean.
The average PM(2.5) mass concentrations for land and sea breeze samples were 25+/
1.0 and 26+/-1.0 microg m(-3), respectively. The average sum of the ion
concentrations (NH(4)(+), SO(4)(2-), NO(3)(-), Na(+), Cl(-)) were 10 and 11.8
microg m(-3) for the samples taken during land and sea breeze periods. The
average total carbon concentrations were 6.0 and 5.3 microg m(-3) for land and
sea breeze periods. The mass of sulfate in particles of ocean origin, 3.3+/-2.8
microg m(-3), is marginally higher than those originating from the land, 2.0+/
0.8 microg m(-3), presumably as a result of the conversion of SO(2) recirculated
from the city. The fraction of sulfate, nitrate and ammonium ions in rainwater
samples is almost a factor of two higher than the fraction measured on filtered
air samples. The rainwater also contains significant concentrations of elemental
and organic carbon. This study, although extending over a period of only 15 days,
with limited chemical samples, suggests that recirculation of anthropogenic
particles from coastal cities should be taken into consideration when diagnosing
and predicting air quality in such regions.
PMID- 17028078
TI - Immune responses generated by Lactobacillus as a carrier in DNA immunization
against foot-and-mouth disease virus.
AB - To exploit Lactobacillus acidophilus as a carrier in DNA immunization against
foot-and-mouth disease virus (FMDV), a recombinant eukaryotic expression plasmid
(pRc/CMV2-VP1-Rep. 8014) harboring pRc/CMV2 vector, the FMDV VP1 gene, and a
replication origin from Lactobacillus plantarum ATCC 8014 strain was constructed.
To detect the VP1 protein, pRc/CMV2-VP1-Rep. 8014 was expressed in PK 15 cells
and transfected into a L. acidophilus SW1 strain (L. acidophilus SFMD-1). To
evaluate the immunization effect of L. acidophilus SFMD-1, anti-FMDV VP1
antibody, T-cell proliferation, antigen-specific delayed-type hypersensitivity
(DTH), and tissue distribution were investigated using intramuscular,
intraperitoneal, intranasal, and oral administration delivery routes. The results
showed that L. acidophilus SFMD-1 was able to elicit a detectable antibody level
on day 21. The VP1 antibody levels induced by L. acidophilus SFMD-1 and
commercial inactivated FMDV vaccine rose rapidly to 0.84 and 0.70, respectively,
by day 42, then sustained a high level by day 49. The route of administration had
an impact on the magnitude of the systemic antigen-specific IgG responses, with
intramuscularly applied L. acidophilus SFMD-1 generating the greatest FMDV VP1
antibody response, followed by intraperitoneal, intranasal, and oral
administration delivery routes. Using the T-cell proliferation assay, the
stimulation index of a group immunized with L. acidophilus SFMD-1 reached 2.78
versus 5.08 in a group immunized with pRc/CMV2-VP1-Rep. 8014 plasmid. Mice
immunized with L. acidophilus SFMD-1 were able to induce T-cell-mediated antigen
specific DTH. In addition, the VP1 gene was detected in the muscle, kidney,
spleen, and heart, but not in the liver. The results demonstrate clearly that
Lactobacillus as a carrier is a promising approach of DNA vaccination, and is a
potentially guard against FMDV.
PMID- 17028079
TI - Germination-independent induction of cellular immune response by Bacillus
subtilis spores displaying the C fragment of the tetanus toxin.
AB - Bacillus subtilis spores displaying the tetanus toxin fragment C (TTFC) on their
surface have been previously shown to induce the production of specific IgG and
secretory IgA in mice immunized through the oral or nasal route. Aim of this
study was to analyze whether these spores were also able to induce cellular
immunity, and whether such immune response was dependent on spore germination in
the animal gastro-intestinal tract (GIT). We first developed a germination
defective strain of B. subtilis unable to produce viable cells inside the mouse
GIT. Germination-defective and congenic wild-type spores both expressing TTFC on
their surface were then used to orally immunize Balb/C mice. Both types of spores
induced spleen and mesenteric lymph nodes cell proliferation as well as
production of IFNgamma but not of IL-4 and IL-10 in both districts. Our results
indicate that recombinant spores preferentially induce a strong cell-mediated
immune response with a Th1 phenotype, independently from their ability to
germinate in the GIT.
PMID- 17028080
TI - Molecular characterisation of pneumococcal serotype 16F: Established predominant
carriage and otitis media serotype in the 7vPCV era.
AB - Young Australian Aboriginal children in remote communities experience very high
rates of pneumococcal carriage and otitis media. Prior to introduction of the 7
valent pneumococcal conjugate vaccine (7vPCV, Prevenar), serotype 16F was an
important type found in nasal and ear discharge swabs. Since commencement of
pneumococcal immunisation for Aboriginal infants in 2001, 16F has become the
predominant established serotype in carriage and otitis media in young Aboriginal
children. BOX typing and multi-locus sequence typing revealed a diverse
population of serotype 16F strains, and evidence of potential capsule switching
from a vaccine serotype 4 to a serotype 16F.
PMID- 17028081
TI - The preventable burden of pneumococcal disease in the developing world.
AB - The efficacy of pneumococcal conjugate vaccines (PCV) and their remarkable
success in operational use in North America challenge us to define the burden of
pneumococcal disease and the likely benefits of PCV use in developing countries.
Community-based incidence studies of invasive pneumococcal disease (IPD) and
vaccine probe analyses of efficacy trials suggest there are approximately 814,000
pneumococcal deaths in children aged <5 years in developing countries each year
and 1-4 million episodes of pneumococcal pneumonia in Africa alone. PCV will be
effective where there is a demonstrable burden of IPD attributable to vaccine
serotypes but herd protection and serotype replacement effects are unpredictable
given existing knowledge of pneumococcal epidemiology in developing countries.
Operational use of PCV in well-monitored settings is required to estimate these
effects.
PMID- 17028082
TI - The mental health of Chinese immigrants in Birmingham, UK.
AB - OBJECTIVES: The objectives of this study were to describe the life experiences
associated with migration to the UK and to explore in-depth information about the
process of life adjustment to migration and the circumstances of mental health in
Chinese immigrants living in a large city area. METHOD: A two-part research
strategy using both quantitative and qualitative methods was employed. In the
cross-sectional quantitative survey, 113 Chinese respondents completed a
questionnaire investigating demographic factors, life experiences associated with
migration, proficiency in the English language and mental health status. In the
qualitative phase of the research, interviews were conducted with a further 24
immigrants to explore these factors in more depth. RESULTS: In the questionnaire
survey, over 60% of the group reported symptoms of poor mental health.
Qualitative research shows that for those who were employed in catering,
psychological adjustment was heavily dependent on strong ties with the Chinese
community and there was minimal contact with the host society. By contrast, those
concerned with professional development experienced conflict as a result of a
high perceived need for integration and a recognition of the problems associated
with this. CONCLUSION: The psychological distress experienced by immigrants of
Chinese origin continues to be a largely invisible cause for concern.
PMID- 17028084
TI - What is the extent of prokaryotic diversity?
AB - The extent of microbial diversity is an intrinsically fascinating subject of
profound practical importance. The term 'diversity' may allude to the number of
taxa or species richness as well as their relative abundance. There is
uncertainty about both, primarily because sample sizes are too small. Non
parametric diversity estimators make gross underestimates if used with small
sample sizes on unevenly distributed communities. One can make richness estimates
over many scales using small samples by assuming a species/taxa-abundance
distribution. However, no one knows what the underlying taxa-abundance
distributions are for bacterial communities. Latterly, diversity has been
estimated by fitting data from gene clone libraries and extrapolating from this
to taxa-abundance curves to estimate richness. However, since sample sizes are
small, we cannot be sure that such samples are representative of the community
from which they were drawn. It is however possible to formulate, and calibrate,
models that predict the diversity of local communities and of samples drawn from
that local community. The calibration of such models suggests that migration
rates are small and decrease as the community gets larger. The preliminary
predictions of the model are qualitatively consistent with the patterns seen in
clone libraries in 'real life'. The validation of this model is also confounded
by small sample sizes. However, if such models were properly validated, they
could form invaluable tools for the prediction of microbial diversity and a basis
for the systematic exploration of microbial diversity on the planet.
PMID- 17028085
TI - Cyanobacterial ecotypes in the microbial mat community of Mushroom Spring
(Yellowstone National Park, Wyoming) as species-like units linking microbial
community composition, structure and function.
AB - We have investigated microbial mats of alkaline siliceous hot springs in
Yellowstone National Park as natural model communities to learn how microbial
populations group into species-like fundamental units. Here, we bring together
empirical patterns of the distribution of molecular variation in predominant mat
cyanobacterial populations, theory-based modelling of how to demarcate
phylogenetic clusters that correspond to ecological species and the dynamic
patterns of the physical and chemical microenvironments these populations inhabit
and towards which they have evolved adaptations. We show that putative ecotypes
predicted by the theory-based model correspond well with distribution patterns,
suggesting populations with distinct ecologies, as expected of ecological
species. Further, we show that increased molecular resolution enhances our
ability to detect ecotypes in this way, though yet higher molecular resolution is
probably needed to detect all ecotypes in this microbial community.
PMID- 17028086
TI - The spatial scale of genetic differentiation in a model organism: the wild yeast
Saccharomyces paradoxus.
AB - Little information is presently available on the factors promoting genetic
divergence in eukaryotic microbes. We studied the spatial distribution of genetic
variation in Saccharomyces paradoxus, the wild relative of Saccharomyces
cerevisiae, from the scale of a few centimetres on individual oak trees to
thousands of kilometers across different continents. Genealogical analysis of six
loci shows that isolates from Europe form a single recombining population, and
within this population genetic differentiation increases with physical distance.
Between different continents, strains are more divergent and genealogically
independent, indicating well-differentiated lineages that may be in the process
of speciation. Such replicated populations will be useful for studies in
population genomics.
PMID- 17028087
TI - Biosynthesis of polyunsaturated fatty acids in lower eukaryotes.
AB - Polyunsaturated fatty acids have important structural roles in cell membranes.
They are also intermediates in the synthesis of biologically active molecules
such as eicosanoids, which mediate fever, inflammation, blood pressure and
neurotransmission. Arachidonic and docosahexaenoic acids are essential components
of brain tissues and, through their involvement in the development of neural and
retinal functions, important dietary nutrients for neonatal babies. Lower
eukaryotes are particularly rich in C20-22 polyunsaturated fatty acids. Fungi and
marine microalgae are currently used to produce nutraceutic oils. Other protists
and algae are being studied because of the variability in their enzymes involved
in polyunsaturated fatty acid biosynthesis. Such enzymes could be used as source
for the production of transgenic organisms able to synthesize designed oils for
human diet or, in the case of parasitic protozoa, they might be identified as
putative chemotherapeutic targets. Polyunsaturated fatty acids can be synthesized
by two different pathways: an anaerobic one, by using polyketide synthase related
enzymes, and an aerobic one, which involves the action of elongases and oxygen
dependent desaturases. Desaturases can be classified into three main types,
depending on which of the consecutive steps of polyunsaturated fatty acid
synthesis they are involved with. The enzymes may be specialized to act on:
saturated substrates (type I); mono- and di-unsaturated fatty acids by
introducing additional double bonds at the methyl-end site of the existing double
bonds (type II); or the carboxy half ('front-end') of polyunsaturated ones (type
III). Type III desaturases require the alternating action of elongases. A
description of the enzymes that have been isolated and functionally characterized
is provided, in order to highlight the different pathways found in lower
eukaryotes.
PMID- 17028088
TI - A field study investigating the effects of a rebar-tying machine on trunk
flexion, tool usability and productivity.
AB - A field study with a before-and-after experimental design was conducted to
evaluate the potential reduction in the risk of musculoskeletal injuries to
rodworkers when using an automatic rebar-tying machine. Eleven rodworkers
participated in this experiment. All dependent variables (trunk posture, rebar
tying time and responses to a usability questionnaire) were first measured before
introducing the rebar-tying machine and then after 3 months of usage all
dependent variables were measured again. The results of the study indicated that
working with a rebar-tying machine significantly reduced the magnitude, frequency
and duration of exposure to awkward trunk posture. Tying time was reduced when
participants used the machine. The usability questionnaire indicated that most
participants preferred to use the rebar-tying machine for ground-level rebar
construction. The field study also revealed that the rebar-tying machine is not
limited to the reinforcing trade. The machine can be used for other purposes,
such as tying electrical conduit and attaching radiant heat tube to steel mesh.
Based on trunk posture exposure, rebar-tying time, usability and transferability,
it is concluded that the rebar-tying machine can be an effective tool to reduce
the frequency and duration of severe trunk flexion, improve usability and
increase productivity among concrete reinforcement workers.
PMID- 17028089
TI - Changes in upper extremity biomechanics across different mouse positions in a
computer workstation.
AB - In order to determine differences in biomechanical risk factors across different
mouse positions within computer workstations a repeated measures laboratory study
was completed with 30 adults (15 females 15 males). The subjects performed mouse
intensive tasks during two experiments. One experiment examined three mouse
positions: a standard mouse (SM) position with the mouse directly to the right of
the keyboard; a central mouse (CM) position with the mouse between the keyboard
and the body, positioned in the body's mid-sagittal plane; a high mouse (HM)
position, which simulated using a keyboard drawer with the mouse on the primary
work surface. The second experiment compared two mouse positions: the SM position
and a more central position using a keyboard without a number keypad (NM).
Electrogoniometers and inclinometers measured wrist and upper arm postures and
surface electromyography measured muscle activity of four forearm muscles and
three shoulder muscles. The CM mouse position was found to produce the most
neutral upper extremity posture across all measures. The HM position produced the
least neutral posture and resulted in the highest level of muscle activity.
Compared to the SM position, the NM position reduced wrist extension slightly and
promoted a more neutral shoulder posture. Little difference in muscle activity
was observed between the SM and NM positions. In conclusion, of these alternative
mouse positions, the HM position was the least desirable, whereas the CM position
reduced overall awkward postures associated with mouse-intensive computer tasks.
PMID- 17028090
TI - Y chromosome microdeletion in a case with Klinefelter's Syndrome.
AB - In male infertility, the frequency of genetic factors is high. Klinefelter's
Syndrome is the most frequent sex chromosomal abnormality detected in male
infertility. In this study we report a patient diagnosed with Klinefelter's
Syndrome with a deletion of the Yq interval. The patient was 24-years old with
primary infertility. Semen analyses carried out in triplicate indicated
azoospermia. The plasma leutenizing hormone (LH) and follicle stimulating hormone
(FSH) levels were abnormally high and the testosterone level was lower than the
usual range. Each of his testes had a volume of 3 cc. Peripheral blood karyotype
analysis showed Klinefelter's Syndrome (47, XXY) pattern. Polymerase chain
reaction amplification of DNA was performed using the following primers; AZFa
(sY81, sY82, sY84), AZFb (sY127, sY142, sY164, RBM1), AZFc (CDY, BPY, sY254,
sY255, sY277), AZFd (sY152, sY145, sY153). Analysis revealed a single deletion of
AZFa region (sY84). Deletion of the AZFa region may be an additional factor for
absolute azoospermia in men with Klinefelter's Syndrome. For individuals with
Klinefelter's Syndrome who plan to undergo assisted reproduction techniques, Y
chromosome microdeletion screening can diagnostically be convenient.
PMID- 17028091
TI - Multivariable difference gel electrophoresis and mass spectrometry: a case study
on transforming growth factor-beta and ERBB2 signaling.
AB - Multivariable DIGE/MS was used to investigate proteins altered in expression
and/or post-translational modification in response to activation of transforming
growth factor (TGF)-beta receptors in MCF10A mammary epithelial cells
overexpressing the HER2/Neu (ErbB2) oncogene. Proteome changes were monitored in
response to exogenous TGF-beta over time (0, 8, 24, and 40 h), and proteins were
resolved using medium range (pH 4-7) and narrow range (pH 5.3-6.5) isoelectric
focusing combined with up to 2 mg of protein to allow inspection of lower
abundance proteins. Triplicate samples were prepared independently and analyzed
together across multiple DIGE gels using a pooled sample internal standard to
quantify expression changes with statistical confidence. Unsupervised principle
component analysis and hierarchical clustering of the individual DIGE proteome
expression maps provided independent confirmation of distinct expression patterns
from the individual experiments and demonstrated high reproducibility between
replicate samples. Fifty-nine proteins (including some isoforms) that exhibited
significant kinetic expression changes were identified using mass spectrometry
and database interrogation and were mapped to existing biological networks
involved in TGF-beta signaling. Several proteins with a potential role in breast
cancer, such as maspin and cathepsin D, were identified as novel molecules
associated with TGF-beta signaling.
PMID- 17028093
TI - The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola
hepatica.
AB - OBJECTIVES: The trematocidal properties of a synthetic peroxide, 1,2,4-trioxolane
(OZ78) were determined both in vivo and in vitro. METHODS: Two weeks post
infection Echinostoma caproni-infected mice were administered single oral doses
of 400-1000 mg/kg OZ78. Fasciola hepatica-infected rats were treated orally with
50-400 mg/kg OZ78 3 and 8-9 weeks post-infection. Worm burden reductions were
assessed against untreated control animals. Adult F. hepatica were observed by
scanning electron microscopy (SEM) after recovery from the bile duct of a rat 3
days after administration of a single oral dose of 100 mg/kg OZ78 and after in
vitro exposure to concentrations of 1, 10 and 100 microg/mL OZ78. RESULTS: In the
E. caproni-mouse model 100% worm burden reductions were achieved with a single
oral dose of 1000 mg/kg OZ78. A single dose of 100 mg/kg OZ78 resulted in worm
burden reductions of 100% against juvenile and adult F. hepatica. F. hepatica
recovered from rats 3 days post-treatment displayed feeble activity and some
flukes had died. Typical features revealed by SEM included extensive blebbing and
sloughing. Exposure of F. hepatica to 10-100 microg/mL OZ78 in vitro resulted in
the death of all trematodes. F. hepatica showed focal blebbing and sloughing of
the tegument at all concentrations investigated. CONCLUSIONS: Our data indicate
that OZ78 is highly efficacious against F. hepatica and E. caproni and provide a
sound platform for identification of a synthetic peroxide drug development
candidate against major trematode infections.
PMID- 17028094
TI - Testing the mutant selection window hypothesis with Staphylococcus aureus exposed
to daptomycin and vancomycin in an in vitro dynamic model.
AB - OBJECTIVES: To extend the mutant selection window (MSW) hypothesis to include
antibiotics in addition to fluoroquinolones, the pharmacodynamics of daptomycin
(DAP) and vancomycin (VAN) and their ability to prevent the selection of
resistant Staphylococcus aureus were studied in an in vitro model that simulates
antibiotic concentrations below the MIC, between the MIC and the mutant
prevention concentration (MPC), and above the MPC. METHODS: Two clinical isolates
of S. aureus, S. aureus 866 (MIC(DAP) 0.35, MIC(VAN) 0.7, MPC(DAP) 1.1, MPC(VAN)
2.4 mg/L) and S. aureus 10 (MIC(DAP) 1.1, MIC(VAN) 1.3, MPC(DAP) 5.5, MPC(VAN) 11
mg/L), were exposed for five consecutive days to once-daily daptomycin (half-life
9 h) and twice-daily vancomycin (half-life 6 h) at the ratio of 24 h area under
the concentration-time curve (AUC24) to MIC that varied over a 16- to 30-fold
range. The cumulative antimicrobial effect was expressed by its intensity (I(E)).
Changes in susceptibility and numbers of surviving organisms on agar plates
containing 2x and 4x MIC of daptomycin or vancomycin were monitored daily.
RESULTS: The I(E)-log AUC24/MIC plots were bacterial strain- and antibiotic
independent. This allowed combination of data obtained with both antibiotics and
both organisms. Based on the sigmoid relationship between I(E) and the AUC24/MIC
(r2 = 0.9), the antistaphylococcal effect of the therapeutic doses of daptomycin
(4 and 6 mg/kg) against a hypothetical S. aureus with MIC equal to the MIC90
(AUC24/MIC90 380 and 570 h, respectively) was predicted to be similar to the
effect of two 1 g doses of vancomycin given at a 12 h interval (AUC24/MIC90 200
h). AUC24/MIC relationships of the final-to-initial MIC ratio and logarithm of
the ratio of maximal-to-initial numbers of organisms resistant to 2x and 4x MIC
of daptomycin or vancomycin were bell-shaped and bacterial strain- and antibiotic
independent. Based on these relationships, an AUC24/MIC ratio that protects
against the selection of resistant mutants was predicted at > or = 200 h. This
protective value is less than the AUC24/MIC90s provided by the 4 mg/kg dose and
considerably less than the 6 mg/kg dose of daptomycin, but it is close to the
AUC24/MIC90 provided by two 1 g doses of vancomycin. CONCLUSIONS: These findings
support the MSW hypothesis and suggest comparable antistaphylococcal effects of
clinically achievable AUC24/MIC90s of daptomycin and vancomycin but slightly
better prevention against the selection of resistant S. aureus by daptomycin.
PMID- 17028096
TI - MetaGene: prokaryotic gene finding from environmental genome shotgun sequences.
AB - Exhaustive gene identification is a fundamental goal in all metagenomics
projects. However, most metagenomic sequences are unassembled anonymous
fragments, and conventional gene-finding methods cannot be applied. We have
developed a prokaryotic gene-finding program, MetaGene, which utilizes di-codon
frequencies estimated by the GC content of a given sequence with other various
measures. MetaGene can predict a whole range of prokaryotic genes based on the
anonymous genomic sequences of a few hundred bases, with a sensitivity of 95% and
a specificity of 90% for artificial shotgun sequences (700 bp fragments from 12
species). MetaGene has two sets of codon frequency interpolations, one for
bacteria and one for archaea, and automatically selects the proper set for a
given sequence using the domain classification method we propose. The domain
classification works properly, correctly assigning domain information to more
than 90% of the artificial shotgun sequences. Applied to the Sargasso Sea
dataset, MetaGene predicted almost all of the annotated genes and a notable
number of novel genes. MetaGene can be applied to wide variety of metagenomic
projects and expands the utility of metagenomics.
PMID- 17028095
TI - The Saccharomyces cerevisiae RNA polymerase III recruitment factor subunits Brf1
and Bdp1 impose a strict sequence preference for the downstream half of the TATA
box.
AB - Association of the TATA-binding protein (TBP) with its cognate site within
eukaryotic promoters is key to accurate and efficient transcriptional initiation.
To achieve recruitment of Saccharomyces cerevisiae RNA polymerase III, TBP is
associated with two additional factors, Brf1 and Bdp1, to form the initiation
factor TFIIIB. Previous data have suggested that the structure or dynamics of the
TBP-DNA complex may be altered upon entry of Brf1 and Bdp1 into the complex. We
show here, using the altered specificity TBP mutant TBPm3 and an iterative in
vitro selection assay, that entry of Brf1 and Bdp1 into the complex imposes a
strict sequence preference for the downstream half of the TATA box. Notably, the
selected sequence (TGTAAATA) is a perfect match to the TATA box of the RNA
polymerase III-transcribed U6 small nuclear RNA (SNR6) gene. We suggest that the
selected T*A base pair step at the downstream end of the 8 bp TBP site may
provide a DNA flexure that promotes TFIIIB-DNA complex formation.
PMID- 17028097
TI - Effects of the trinucleotide preceding the self-cleavage site on eggplant latent
viroid hammerheads: differences in co- and post-transcriptional self-cleavage may
explain the lack of trinucleotide AUC in most natural hammerheads.
AB - Eggplant latent viroid (ELVd) can form stable hammerhead structures in its (+)
and (-) strands. These ribozymes have the longest helices I reported in natural
hammerheads, with that of the ELVd (+) hammerhead being particularly stable (5/7
bp are G-C). Moreover, the trinucleotide preceding the self-cleavage site of this
hammerhead is AUA, which together with GUA also found in some natural
hammerheads, deviate from the GUC present in most natural hammerheads including
the ELVd (-) hammerhead. When the AUA trinucleotide preceding the self-cleavage
site of the ELVd (+) hammerhead was substituted by GUA and GUC, as well as by AUC
(essentially absent in natural hammerheads), the values of the self-cleavage rate
constants at low magnesium of the purified hammerheads were: ELVd-(+)-AUC
approximately ELVd-(+)-GUC>ELVd-(+)-GUA> ELVd-(+)-AUA. However, the ELVd-(+)-AUC
hammerhead was the catalytically less efficient during in vitro transcription,
most likely because of the transient adoption of catalytically-inactive
metastable structures. These results suggest that natural hammerheads have been
evolutionary selected to function co-transcriptionally, and provide a model
explaining the lack of trinucleotide AUC preceding the self-cleavage site of most
natural hammerheads. Comparisons with other natural hammerheads showed that the
ELVd-(+)-GUC and ELVd-(+)-AUC hammerheads are the catalytically most active in a
post-transcriptional context with low magnesium.
PMID- 17028098
TI - A high throughput method for genome-wide analysis of retroviral integration.
AB - Retroviral and lentiviral vectors integrate their DNA into the host cell genome
leading to stable transgene expression. Integration preferentially occurs in the
proximity of active genes, and may in some case disturb their activity, with
adverse toxic consequences. To efficiently analyze high numbers of lentiviral
insertion sites in the DNA of transduced cells, we developed an improved high
throughput method called vector integration tag analysis (VITA). VITA is based on
the identification of Genomic Tags associated to the insertion sites, which are
used as signatures of the integration events. We use the capacity of MmeI to
cleave DNA at a defined distance of its recognition site, in order to generate 21
bp long tags from libraries of junction fragments between vector and cellular
DNA. The length of the tags is sufficient in most cases, to identify without
ambiguity an unique position in the human genome. Concatenation, cloning and
sequencing of the tags allow to obtain information about 20-25 insertion sites in
a single sequencing reaction. As a validation of this method, we have
characterized 1349 different lentiviral vector insertion sites in transduced HeLa
cells, from only 487 sequencing reactions, with a background of <2% false
positive tags.
PMID- 17028099
TI - DeepSAGE--digital transcriptomics with high sensitivity, simple experimental
protocol and multiplexing of samples.
AB - Digital transcriptomics with pyrophosphatase based ultra-high throughput DNA
sequencing of di-tags provides high sensitivity and cost-effective gene
expression profiling. Sample preparation and handling are greatly simplified
compared to Serial Analysis of Gene Expression (SAGE). We compare DeepSAGE and
LongSAGE data and demonstrate greater power of detection and multiplexing of
samples derived from potato. The transcript analysis revealed a great abundance
of up-regulated potato transcripts associated with stress in dormant potatoes
compared to harvest. Importantly, many transcripts were detected that cannot be
matched to known genes, but is likely to be part of the abiotic stress-response
in potato.
PMID- 17028100
TI - Expression of C-terminal deleted p53 isoforms in neuroblastoma.
AB - The tumor suppressor gene, p53, is rarely mutated in neuroblastomas (NB) at the
time of diagnosis, but its dysfunction could result from a nonfunctional
conformation or cytoplasmic sequestration of the wild-type p53 protein. However,
p53 mutation, when it occurs, is found in NB tumors with drug resistance acquired
over the course of chemotherapy. As yet, no study has been devoted to the
function of the specific p53 mutants identified in NB cells. This study includes
characterization and functional analysis of p53 expressed in eight cell lines:
three wild-type cell lines and five cell lines harboring mutations. We identified
two transcription-inactive p53 variants truncated in the C-terminus, one of which
corresponded to the p53beta isoform recently identified in normal tissue by
Bourdon et al. [J. C. Bourdon, K. Fernandes, F. Murray-Zmijewski, G. Liu, A.
Diot, D. P. Xirodimas, M. K. Saville and D. P. Lane (2005) Genes Dev., 19, 2122
2137]. Our results show, for the first time, that the p53beta isoform is the only
p53 species to be endogenously expressed in the human NB cell line SK-N-AS,
suggesting that the C-terminus truncated p53 isoforms may play an important role
in NB tumor development.
PMID- 17028101
TI - Functional characterization of a 48 kDa Trypanosoma brucei cap 2 RNA
methyltransferase.
AB - Kinetoplastid mRNAs possess a unique hypermethylated cap 4 structure derived from
the standard m7GpppN cap structure, with 2'-O methylations on the first four
ribose sugars and additional base methylations on the first adenine and the
fourth uracil. While the enzymes responsible for m7GpppN cap 0 formations has
been characterized in Trypanosoma brucei, the mechanism of cap 4 methylation and
the role of the hypermethylated structure remain unclear. Here, we describe the
characterization of a 48 kDa T.brucei 2'-O nucleoside methyltransferase (TbCom1).
Recombinant TbCom1 transfers the methyl group from S-adenosylmethionine (AdoMet)
to the 2'-OH of the second nucleoside of m7GpppNpNp-RNA to form m7GpppNpNmp-RNA.
TbCom1 is also capable of converting cap 1 RNA to cap 2 RNA. The methyl transfer
reaction is dependent on the m7GpppN cap, as the enzyme does not form a stable
interaction with GpppN-terminated RNA. Mutational analysis establishes that the
TbCom1 and vaccinia virus VP39 methyltransferases share mechanistic similarities
in AdoMet- and cap-recognition. Two aromatic residues, Tyr18 and Tyr187, may
participate in base-stacking interactions with the guanine ring of the cap, as
the removal of each of these aromatic side-chains abolishes cap-specific RNA
binding.
PMID- 17028102
TI - RusA Holliday junction resolvase: DNA complex structure--insights into
selectivity and specificity.
AB - We have determined the structure of a catalytically inactive D70N variant of the
Escherichia coli RusA resolvase bound to a duplex DNA substrate that reveals
critical protein-DNA interactions and permits a much clearer understanding of the
interaction of the enzyme with a Holliday junction (HJ). The RusA enzyme cleaves
HJs, the fourway DNA branchpoints formed by homologous recombination, by
introducing symmetrical cuts in the phosphodiester backbone in a Mg2+ dependent
reaction. Although, RusA shows a high level of selectivity for DNA junctions,
preferring to bind fourway junctions over other substrates in vitro, it has also
been shown to have appreciable affinity for duplex DNA. However, RusA does not
show DNA cleavage activity with duplex substrates. Our structure suggests the
possible basis for structural selectivity as well as sources of the sequence
specificity observed for DNA cleavage by RusA.
PMID- 17028103
TI - August 2003 heat wave in France: risk factors for death of elderly people living
at home.
AB - The August 2003 heat wave in France resulted in many thousands of excess deaths
particularly of elderly people. Individual and environmental risk factors for
death among the community-dwelling elderly were identified. We conducted a case
control survey and defined cases as people aged 65 years and older who lived at
home and died from August 8 through August 13 from causes other than accident,
suicide, or surgical complications. Controls were matched with cases for age,
sex, and residential area. Interviewers used questionnaires to collect data.
Satellite pictures provided profiles of the heat island characteristics around
the homes. Lack of mobility was a major risk factor along with some pre-existing
medical conditions. Housing characteristics associated with death were lack of
thermal insulation and sleeping on the top floor, right under the roof. The
temperature around the building was a major risk factor. Behaviour such as
dressing lightly and use of cooling techniques and devices were protective
factors. These findings suggest people with pre-existing medical conditions were
likely to be vulnerable during heat waves and need information on how to adjust
daily routines to heat waves. In the long term, building insulation and urban
planning must be adapted to provide protection from possible heat waves.
PMID- 17028104
TI - How to change environmental conditions for health.
AB - Since the Lalonde report, contemporary public-health theory has given steadily
more attention to the role of environments in influencing health status.
Environments, both social and physical, influence health directly or through
complex interactions with behavior, genetics and health-care systems. They are
also important for public-health because environments are the complex systems
through which people are both empowered and exercise their empowerment. If public
health professionals are to play a significant role in influencing environments
for health, they need analytical instruments that enable them to link specific
environmental conditions with the actions necessary to improve them. These
instruments must also enable public-health professionals to identify points of
leverage for stimulating key actors to take the actions necessary to make
environments more promoting of health. This article first presents one such
analytical instrument. Then, building on examples relating to socio-economic
health inequities, the analytical instrument is applied to reveal how it can add
value to health professionals' effectiveness in planning interventions for more
health-promoting environments.
PMID- 17028105
TI - Physical activity to prevent obesity in young children: cluster randomised
controlled trial.
AB - OBJECTIVE: To assess whether a physical activity intervention reduces body mass
index in young children. DESIGN: Cluster randomised controlled single blinded
trial over 12 months. SETTING: Thirty six nurseries in Glasgow, Scotland.
PARTICIPANTS: 545 children in their preschool year, mean age 4.2 years (SD 0.2)
at baseline. INTERVENTION: Enhanced physical activity programme in nursery (three
30 minute sessions a week over 24 weeks) plus home based health education aimed
at increasing physical activity through play and reducing sedentary behaviour.
MAIN OUTCOME MEASURE: Body mass index, expressed as a standard deviation score
relative to UK 1990 reference data. Secondary measures were objectively measured
physical activity and sedentary behaviour; fundamental movement skills; and
evaluation of the process. RESULTS: Group allocation had no significant effect on
the primary outcome measure at six and 12 months or on measures of physical
activity and sedentary behaviour by accelerometry. Children in the intervention
group had significantly higher performance in movement skills tests than control
children at six month follow-up (P=0.0027; 95% confidence interval 0.3 to 1.3)
after adjustment for sex and baseline performance. CONCLUSIONS: Physical activity
can significantly improve motor skills but did not reduce body mass index in
young children in this trial. TRIAL REGISTRATION: Current Controlled Trials
ISRCTN36363490.
PMID- 17028107
TI - Gas diffusion and alveolar-capillary unit in chronic heart failure.
AB - AIMS: Alveolar gas diffusion (DLCO) is impaired in chronic heart failure (CHF).
Diffusion depends on membrane diffusion (DM) and the amount of blood
participating in gas exchange (VC). How DM, VC, and the alveolar-capillary unit
behave in relationship to CHF severity is unknown. METHODS AND RESULTS: We
measured pulmonary function, including DLCO, DM, VC, and alveolar volume (VA), in
191 CHF patients in NYHA class I-III. CHF patients were grouped accordingly to
peak exercise oxygen uptake (pVO(2)): group <12 mL/min/kg (n=24), group 12-16
(n=76), group 16-20 (n=64), and group >20 (n=27). DLCO, DM, VC, and VA were
lowest in severe CHF and were linearly related to pVO(2) (DLCO, r=0.577, P<0.001;
DM, r=0.490, P<0.001; VC, r=0.216, P<0.01; VA, r=0.565, P<0.01). DM/VC ratio, an
index of the alveolar-capillary unit efficiency, was higher in group <12 (0.49+/
0.39 mL/min/mmHg/mL) and >20 (0.46+/-0.29), compared with 12-16 (0.34+/-0.19) and
16-20 (0.35+/-0.17). CONCLUSION: DLCO progressively worsens as CHF severity
increases due to reduction in lung tissue participating to gas exchange (low VC
and VA). In severe CHF, the few working alveolar-capillary units are the most
efficient as shown by the high DM/VC. This is useful for maintaining gas exchange
efficiency in severe CHF.
PMID- 17028106
TI - Cochrane reviews compared with industry supported meta-analyses and other meta
analyses of the same drugs: systematic review.
AB - OBJECTIVE: To compare the methodological quality and conclusions in Cochrane
reviews with those in industry supported meta-analyses and other meta-analyses of
the same drugs. DESIGN: Systematic review comparing pairs of meta-analyses that
studied the same two drugs in the same disease and were published within two
years of each other. DATA SOURCES: Cochrane Database of Systematic Reviews (2003,
issue 1), PubMed, and Embase. DATA EXTRACTION: Two observers independently
extracted data and used a validated scale to judge the methodological quality of
the reviews. RESULTS: 175 of 1596 Cochrane reviews had a meta-analysis that
compared two drugs. Twenty four meta-analyses that matched the Cochrane reviews
were found: eight were industry supported, nine had undeclared support, and seven
had no support or were supported by non-industry sources. On a 0-7 scale, the
median quality score was 7 for Cochrane reviews and 3 for other reviews (P <
0.01). Compared with industry supported reviews and reviews with undeclared
support, Cochrane reviews had more often considered the potential for bias in the
review--for example, by describing the method of concealment of allocation and
describing excluded patients or studies. The seven industry supported reviews
that had conclusions recommended the experimental drug without reservations,
compared with none of the Cochrane reviews (P = 0.02), although the estimated
treatment effect was similar on average (z = 0.46, P = 0.64). Reviews with
undeclared support and reviews with not for profit support or no support had
conclusions that were similar in cautiousness to the Cochrane reviews.
CONCLUSIONS: Industry supported reviews of drugs should be read with caution as
they were less transparent, had few reservations about methodological limitations
of the included trials, and had more favourable conclusions than the
corresponding Cochrane reviews.
PMID- 17028108
TI - Platelets and heart failure.
AB - Heart failure is associated with increased risk of venous thromboembolism,
stroke, and sudden death. Platelet abnormalities have been well described in
heart failure but the significance of platelets in contributing to the
thromboembolic complications of heart failure remains uncertain. Furthermore, the
role of antiplatelet agents in heart failure remains unclear. This review will
focus on platelet activation and the role of platelet dysfunction in heart
failure, with particular regard to pathophysiology and outcome. The effects of
heart failure therapeutics on platelet function and antiplatelet therapy in heart
failure will also be discussed.
PMID- 17028109
TI - Sweet and sour coronary heart disease: results from the China Heart Survey.
PMID- 17028110
TI - Toll the bell for another genetic association?
PMID- 17028111
TI - Guidelines on the management of stable angina pectoris.
PMID- 17028113
TI - A major susceptibility locus for HTLV-1 infection in childhood maps to chromosome
6q27.
AB - Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) is a human oncoretrovirus
causing adult T-cell leukemia/lymphoma and chronic neuromyelopathy. We previously
showed by segregation analysis that a dominant gene controls HTLV-1 infection
through breast-feeding in children of African origin. Here, we report the mapping
of this locus by a genome-wide linkage analysis based on the genetic model
provided by segregation analysis. Five pedigrees of African origin with HTLV-1
seropositive children were included in the study. Significant evidence for
linkage (LOD score of 3.36, P=0.00004) was obtained for chomosomal region 6q27
when using the robust analysis including only HTLV-1-infected subjects. When HTLV
1 seronegative children born to infected mothers were added in the analysis, a
maximum LOD score of 2.79 (P=0.0002) was obtained for chomosome 2p25. This result
was mostly due to the largest pedigree of our sample, which alone gave a LOD
score of 2.90 (P=0.00013). We further excluded the role of exonic variants of two
candidate genes located in the linked regions, CCR6 (chemokine receptor 6) in
6q27 and ID2 (inhibitor of DNA binding 2) in 2p25. Our results, mapping a major
susceptibility locus to chromosome 6q27 and suggesting genetic heterogeneity with
another locus at 2p25, pave the way to the determination of the molecular basis
of predisposition to HTLV-1 infection in children.
PMID- 17028112
TI - Analysis of Nsdhl-deficient embryos reveals a role for Hedgehog signaling in
early placental development.
AB - The X-linked Nsdhl gene encodes a sterol dehydrogenase involved in cholesterol
biosynthesis. Mutations in this gene cause the male lethal phenotypes in human
CHILD syndrome and bare patches (Bpa) mice. Affected male embryos for several
mutant Nsdhl alleles die in mid-gestation with a thin and poorly vascularized
placental labyrinth. The timing and specific abnormalities noted suggest a defect
in one or more developmental signaling pathways as a possible mechanism. Here, we
examined the possible involvement of the hedgehog signaling pathway in the
placental pathology of Nsdhl mutants using a transgenic mouse line
(Ptch1(tm1Mps)) that contains a lacZ reporter under the control of the promoter
for Ptch1, the gene that encodes the major hedgehog receptor. We demonstrate
expression of Ptch1 in allantoic mesoderm of the placenta from wild-type mid
gestation embryos. The evidence suggests that the signaling is induced by Indian
hedgehog that is produced by distal (ectoplacental) visceral endoderm cells that
migrate into the allantoic mesoderm before embryonic day 10.0. Using a
ubiquitously expressed, X-linked lacZ transgene that undergoes normal X
inactivation, we demonstrate that the placental defects in Nsdhl/+ female embryos
are non-cell autonomous. Further, affected placentas from mutant Nsdhl(Bpa-8H)
male embryos demonstrate markedly decreased or no Ptch1-lacZ staining and no
migration of Ihh expressing cells into the developing placenta. These data
strongly implicate the hedgehog signaling pathway in the pathogenesis of the
placental defects in NSDHL deficiency and provide evidence for a role for the
hedgehog pathway in the development of a functional mammalian placenta.
PMID- 17028114
TI - A functional M196R polymorphism of tumour necrosis factor receptor type 2 is
associated with systemic lupus erythematosus: a case-control study and a meta
analysis.
AB - OBJECTIVES: To perform a case-control study of a functional M196R polymorphism of
tumour necrosis factor receptor type 2 (TNF-RII) in a Japanese population and a
meta-analysis of all published reports on the polymorphism to investigate the
association of the M196R polymorphism of TNF-RII with systemic lupus
erythematosus (SLE). METHODS: The functional M196R polymorphism of TNF-RII was
genotyped by using polymerase chain reaction combined with the subsequent single
strand conformation polymorphism (PCR-SSCP) analysis for screening, followed by
nucleotide sequencing for confirmation. A total of 331 patients and 359 controls
were subjected to a case-control study. A meta-analysis of the available case
control studies including all published data as well as our own data was
performed to investigate the association of the functional M196R polymorphism of
TNF-RII with SLE. RESULTS: Our case-control study did not show any significant
association of a functional M196R polymorphism of TNF-RII with SLE, although
there was a trend towards association. A meta-analysis of seven case-control
studies in eight different ethnic populations including our own showed that
196M/R and 196R/R genotypes combined was significantly associated with an
increased risk of SLE (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.04 to
1.60; p = 0.02). Stratification by ethnicity showed a more significant
association in Asians, including Japanese, Korean and Vietnamese (OR 1.40, 95% CI
1.10 to 1.78; p = 0.006). The effect of the 196R allele on SLE was not clear in
Caucasians. CONCLUSIONS: The 196R allele of the functional M196R polymorphism of
TNF-RII is a risk factor for SLE, especially in the Asian population.
PMID- 17028115
TI - Lumbar disc degeneration: association between osteophytes, end-plate sclerosis
and disc space narrowing.
AB - BACKGROUND: Lumbar disc degeneration is characterised radiologically by the
presence of osteophytes, end-plate sclerosis and disc space narrowing. AIM: To
determine the strength of the association between increasing severity of
combinations of these features in a population sample of men and women. METHODS:
Men and women aged >or=50 years were recruited from a primary care-based
community health index in Aberdeen, UK. Participants had lateral spinal
radiographs performed according to a standard protocol. The intervertebral disc
spaces (L1/2-L4/5) were evaluated for the presence of anterior osteophytes, end
plate sclerosis and disc space narrowing using a graded semiquantitative score
(grade 0-3). Log linear modelling was used to determine the associations
(pairwise) between increasing severity of these features, with the results
expressed as beta coefficients and 95% confidence intervals (CIs). RESULTS: There
were 286 men (mean age 65.3 years) and 299 women (mean age 65.2 years) with
spinal radiographs, yielding a total of 2340 assessable lumbar vertebral levels.
In all, 73% of vertebral levels had evidence of osteophytes, 26% of sclerosis and
37% of disc space narrowing. Increasing severity of osteophyte grade was
associated with an increasing severity both of sclerosis and of disc space
narrowing, whereas the severity of sclerosis was associated with the severity of
narrowing. This was true at all vertebral levels. The strongest association,
however, was between osteophytes and sclerosis (beta coefficient = 2.7, 95% CI
2.4 to 3.1). For sclerosis and narrowing the beta coefficient was 1.9 (95% CI 1.7
to 2.1), whereas for osteophytes and narrowing the beta coefficient was much
weaker at 1.2 (95% CI 1.1 to 1.3). There was no important influence of vertebral
level on any of these associations. CONCLUSION: The association between
increasing severity of osteophytes and end-plate sclerosis is stronger than for
other combinations of radiographic features of lumbar disc degeneration.
PMID- 17028116
TI - Diagnosis and treatment of dural carotid-cavernous fistulas: a consecutive series
of 27 patients.
AB - OBJECTIVES: To report clinical characteristics, angiographical findings and
results of endovascular treatment of patients presenting with dural carotid
cavernous fistulas (DCCFs). METHOD: Retrospective analysis of 27 consecutive
patients with DCCF referred to a specialised interventional neuroradiology
department. RESULTS: Orbital and neuro-ophthalmological symptoms were the most
common clinical presentation at diagnosis (n = 25). The venous drainage of the
fistula involved the ipsilateral superior ophthalmic vein in 24 patients, the
contralateral cavernous sinus in 6 and a leptomeningeal vein in 5 patients.
Thrombosis of at least one petrosal sinus was found in 23 patients. 7 patients
did not receive endovascular treatment: 3 had spontaneous DCCF obliteration, and
4 had only minor clinical symptoms and no leptomeningeal venous drainage on an
angiogram. 20 patients received endovascular treatment via either a transvenous
(n = 16) or a transarterial approach (n = 4). Complete occlusion of the fistula
was obtained in 14 of 16 (87%) patients treated by the transvenous approach and
in 1 of 4 (25%) patients treated by the transarterial approach. 16 patients had
early clinical improvement after endovascular treatment. One patient had a
cerebral haemorrhage after transvenous embolisation of a DCCF with leptomeningeal
drainage. On follow-up, all patients treated by the transarterial route remained
symptomatic, whereas 10 of 14 (71%) patients cured by the transvenous route were
asymptomatic. CONCLUSIONS: Transvenous embolisation is a safe and efficient
endovascular approach to treat patients with DCCF. However, this technique
requires a long learning curve.
PMID- 17028117
TI - Functional connectivity of the prefrontal cortex in Huntington's disease.
AB - BACKGROUND: Huntington's disease is a progressive neurodegenerative disorder that
results in deterioration and atrophy of various brain regions. AIM: To assess the
functional connectivity between prefrontal brain regions in patients with
Huntington's disease, compared with normal controls, using functional magnetic
resonance imaging. PATIENTS AND METHODS: 20 patients with Huntington's disease
and 17 matched controls performed a Simon task that is known to activate lateral
prefrontal and anterior cingulate cortical regions. The functional connectivity
was hypothesised to be impaired in patients with Huntington's disease between
prefrontal regions of interest, selected from both hemispheres, in the anterior
cingulate and dorsal lateral prefrontal cortex. RESULTS: Controls showed a
dynamic increase in interhemispheric functional connectivity during task
performance, compared with the baseline state; patients with Huntington's
disease, however, showed no such increase in prefrontal connectivity. Overall,
patients with Huntington's disease showed significantly impaired functional
connectivity between anterior cingulate and lateral prefrontal regions in both
hemispheres compared with controls. Furthermore, poor task performance was
predicted by reduced connectivity in patients with Huntington's disease between
the left anterior cingulate and prefrontal regions. CONCLUSIONS: This finding
represents a loss of synchrony in activity between prefrontal regions in patients
with Huntington's disease when engaged in the task, which predicted poor task
performance. Results show that functional interactions between critical
prefrontal regions, necessary for cognitive performance, are compromised in
Huntington's disease. It is speculated whether significantly greater levels of
activation in patients with Huntington's disease (compared with controls)
observed in several brain regions partially compensate for the otherwise
compromised interactions between cortical regions.
PMID- 17028118
TI - Corpus callosum atrophy is associated with mental slowing and executive deficits
in subjects with age-related white matter hyperintensities: the LADIS Study.
AB - BACKGROUND: Previous research has indicated that corpus callosum atrophy is
associated with global cognitive decline in neurodegenerative diseases, but few
studies have investigated specific cognitive functions. OBJECTIVE: To investigate
the role of regional corpus callosum atrophy in mental speed, attention and
executive functions in subjects with age-related white matter hyperintensities
(WMH). METHODS: In the Leukoaraiosis and Disability Study, 567 subjects with age
related WMH were examined with a detailed neuropsychological assessment and
quantitative magnetic resonance imaging. The relationships of the total corpus
callosum area and its subregions with cognitive performance were analysed using
multiple linear regression, controlling for volume of WMH and other confounding
factors. RESULTS: Atrophy of the total corpus callosum area was associated with
poor performance in tests assessing speed of mental processing--namely, trail
making A and Stroop test parts I and II. Anterior, but not posterior, corpus
callosum atrophy was associated with deficits of attention and executive
functions as reflected by the symbol digit modalities and digit cancellation
tests, as well as by the subtraction scores in the trail making and Stroop tests.
Furthermore, semantic verbal fluency was related to the total corpus callosum
area and the isthmus subregion. CONCLUSIONS: Corpus callosum atrophy seems to
contribute to cognitive decline independently of age, education, coexisting WMH
and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe
mediated executive functions and attention, whereas overall corpus callosum
atrophy is associated with the slowing of processing speed.
PMID- 17028119
TI - A magnetic resonance imaging study of patients with Parkinson's disease with mild
cognitive impairment and dementia using voxel-based morphometry.
AB - BACKGROUND: Dementia is common in Parkinson's disease, but the underlying brain
pathology is not yet fully understood. AIM: To examine the changes in the brain
of patients with Parkinson's disease with mild cognitive impairment (MCI) and
dementia, using structural magnetic resonance imaging. METHODS: Using voxel-based
morphometry, the grey matter atrophy on brain images of patients with Parkinson's
disease and dementia (PDD; n = 16) and Parkinson's disease without dementia
(PDND; n = 20), and healthy elderly subjects (n = 20) was studied. In the PDND
group, 12 subjects had normal cognitive status and 8 had MCI. Standardised rating
scales for motor, cognitive and psychiatric symptoms were used. RESULTS:
Widespread areas of cortical atrophy were found in patients with PDD compared
with normal controls (in both temporal and frontal lobes and in the left parietal
lobe). Grey matter reductions were found in frontal, parietal, limbic and
temporal lobes in patients with PDD compared with those with PDND. In patients
with PDND with MCI, areas of reduced grey matter in the left frontal and both
temporal lobes were found. CONCLUSION: These findings show that dementia in
Parkinson's disease is associated with structural neocortical changes in the
brain, and that cognitive impairment in patients with PDND may be associated with
structural changes in the brain. Further studies with larger groups of patients
are needed to confirm these findings.
PMID- 17028120
TI - Fatal encephalopathy after an isolated overdose of cocaine.
PMID- 17028121
TI - Acute disseminated encephalomyelitis: a follow-up study in Taiwan.
AB - BACKGROUND: Acute-disseminated encephalomyelitis (ADEM) is a demyelinating
disorder of the central nervous system, whose epidemiology, clinical
presentations and functional outcome are incompletely understood in Asian
populations. OBJECTIVE: To assess the clinical presentations, predisposing
factors and functional outcome of ADEM in Taiwan. METHODS: 50 patients initially
diagnosed with ADEM (male, 19; female, 31) were enrolled from 1991 to 2005.
Diagnosis of ADEM or multiple sclerosis was established during a follow-up period
of 2-120 months. 8 adult patients were noted to have taken the immunomodulatory
drug, levamisole, within 3 months before onset of symptoms. The remaining 42
patients (male, 17; female, 25) were categorised by age as children (<16 years, n
= 12), young adults (16-49 years, n = 21) and elderly adults (> or =50 years, n =
9). The clinical manifestations, predisposing factors and radiological findings
were compared between different age groups and adult patients with or without
levamisole use. Functional outcome was compared by a log-rank test. RESULTS:
Preceding upper respiratory tract infection was evident in 21 (50%) patients and
only one young-adult patient had received Rubella vaccine immunisation. The
frequency of fever was higher in children (p = 0.04) and psychiatric symptoms
were more prevalent in elderly patients (p = 0.03). Functional recovery was
faster in children than in adults (p = 0.002). Initial Expanded Disability Status
Scale score (odds ratio (OR) 1.9, p = 0.03) and no fever (OR 0.04, p = 0.06) were
associated with poor outcome (modified Rankin scale > or =2). After a mean (SD)
follow-up of 31.8 (9.9) months, 4 (9.5%) patients developed multiple sclerosis (3
(25%) children, 1 (4.7%) young adult, p = 0.03). The neurological disability,
radiological and cerebrospinal fluid findings did not differ between patients
with and without levamisole use. One elderly adult patient previously receiving
levamisole developed multiple sclerosis of relapse-remitting type after a mean
follow-up period of 36.9 months. CONCLUSION: The clinical presentations,
functional outcome and risk of developing multiple sclerosis differed between
different age groups. Functional recovery was faster in children than in adults.
Poor functional outcome was related to initial high Expanded Disability Status
Scale score and absence of fever.
PMID- 17028122
TI - Temporal changes in cerebral tissue oxygenation with cerebrovascular pressure
reactivity in severe traumatic brain injury.
AB - OBJECTIVE: To investigate the temporal relationship between cerebrovascular
pressure reactivity and brain tissue oxygenation in patients with severe head
injury. METHODS: In 40 patients, brain tissue oxygenation and intracranial
pressure were monitored. Time-averaged values for intracranial pressure (ICP),
mean arterial pressure (MAP), cerebral perfusion pressure (CPP) and brain tissue
oxygenation (PtiO2) were computed. The pressure reactivity index (PRx) was
calculated. The mean values of the variables were obtained at the 6-h and 72-h
post-injury time points, and the difference between the two time points for each
of the variables was denoted as delta (delta). RESULTS: Of the 40 patients, 32
were survivors and 8 were non-survivors. Statistically significant differences
were present between these two groups with regard to deltaMAP (p = 0.013), ICP at
6 h (p = 0.027), CPP at 72 h (p = 0.018), deltaCPP (p = 0.033), PRx at 6 h (p =
0.029), PRx at 72 h (p = 0.002), PtiO2 at 72 h (p < 0.0005) and deltaPtiO2 (p =
0.023) values, reflecting an improvement with time in survivors and a
deterioration with time in non-survivors. In non-survivors, the magnitude of
change in PtiO2 and CPP with time correlated in a negative linear fashion (p =
0.042 and 0.029, respectively) with the change in PRx with time, whereas no such
relationship was seen in survivors. CONCLUSION: The severity of brain tissue
oxygenation derangement correlates with increasing cerebrovascular
dysautoregulation in patients succumbing to severe head injury, supporting the
utility of PRx as a monitoring variable and the rationale for a target-driven
approach to head injury management.
PMID- 17028123
TI - A case of intrahepatic cholangiocarcinoma involving the proper hepatic artery.
PMID- 17028124
TI - International comparisons of cumulative risk of oesophagus cancer, from cancer
incidence in five continents Vol. VIII.
PMID- 17028125
TI - Outpatient liver biopsy: a prospective evaluation of 500 cases.
PMID- 17028126
TI - Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin
treatment for Helicobacter pylori eradication: the HYPER Study.
AB - BACKGROUND: Triple therapy is recommended for Helicobacter pylori eradication,
yet consensus on the duration of treatment is lacking. AIM: To compare the
efficacy and safety of 1- and 2-week regimens of omeprazole, amoxicillin and
clarithromycin in a large, multicentre, double-blind and randomised study.
METHODS: A total of 909 H pylori-positive patients with duodenal ulcer, enrolled
in 81 endoscopy units in Italy, were randomised to receive omeprazole,
amoxicillin and clarithromycin for either 1 week (OAC1W) or 2 weeks (OAC2W) or
omeprazole and amoxicillin for 2 weeks. H pylori eradication was assessed by
histological examination and carbon-13 urea breath test 4 weeks after treatment.
RESULTS: Both the intention-to-treat (ITT; n = 907) and per protocol (PP; n =
661) analyses showed no significant differences between the eradication rates of
OAC1W (ITT 79.7%; PP 83.6%) and OAC2W (ITT 81.7%; PP 84.9%; ITT p = 0.53; PP p =
0.71). Both triple omeprazole, amoxicillin and clarithromycin regimens gave
significantly higher eradication rates compared with omeprazole and amoxicillin
treatment (ITT 44.6%; PP 42.8%; p<0.001). Poor compliance was reported in 18.6%,
17.3% and 15.1% (p = 0.51) of patients for OAC2W, OAC1W and omeprazole and
amoxicillin, respectively. Adverse events occurred in 9.9% and 9.6% (p = 0.88) of
patients for OAC2W and OAC1W, respectively, and in 5.9% for omeprazole and
amoxicillin (p = 0.11). CONCLUSIONS: 1-week and 2-week triple treatments for H
pylori eradication are similar in terms of efficacy, safety and patient
compliance.
PMID- 17028127
TI - Ulcerative colitis: no rise in mortality in a European-wide population based
cohort 10 years after diagnosis.
AB - BACKGROUND: Population based studies have revealed varying mortality for patients
with ulcerative colitis but most have described patients from limited
geographical areas who were diagnosed before 1990. AIMS: To assess overall
mortality in a European cohort of patients with ulcerative colitis, 10 years
after diagnosis, and to investigate national ulcerative colitis related mortality
across Europe. METHODS: Mortality 10 years after diagnosis was recorded in a
prospective European-wide population based cohort of patients with ulcerative
colitis diagnosed in 1991-1993 from nine centres in seven European countries.
Expected mortality was calculated from the sex, age and country specific
mortality in the WHO Mortality Database for 1995-1998. Standardised mortality
ratios (SMR) and 95% confidence intervals (CI) were calculated. RESULTS: At
follow-up, 661 of 775 patients were alive with a median follow-up duration of 123
months (107-144). A total of 73 deaths (median follow-up time 61 months (1-133))
occurred compared with an expected 67. The overall mortality risk was no higher:
SMR 1.09 (95% CI 0.86 to 1.37). Mortality by sex was SMR 0.92 (95% CI 0.65 to
1.26) for males and SMR 1.39 (95% CI 0.97 to 1.93) for females. There was a
slightly higher risk in older age groups. For disease specific mortality, a
higher SMR was found only for pulmonary disease. Mortality by European region was
SMR 1.19 (95% CI 0.91 to 1.53) for the north and SMR 0.82 (95% CI 0.45-1.37) for
the south. CONCLUSIONS: Higher mortality was not found in patients with
ulcerative colitis 10 years after disease onset. However, a significant rise in
SMR for pulmonary disease, and a trend towards an age related rise in SMR, was
observed.
PMID- 17028128
TI - High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in
inflammatory bowel disease.
AB - BACKGROUND: It is not clear which species of bacteria may be involved in
inflammatory bowel disease (IBD). One way of determining which bacteria might be
likely candidates is to use culture-independent methods to identify
microorganisms that are present in diseased tissues but not in controls. AIMS:
(1) To assess the diversity of microbial communities of biopsy tissue using
culture-independent methods; (2) to culture the bacteria found in the tissues of
patients with IBD but not in the controls; (3) to identify potential virulence
factors associated with cultured bacteria. METHODS: 84 biopsy specimens were
collected from 15 controls, 13 patients with Crohn's disease (CD) and 19 patients
with ulcerative colitis (UC) from a population-based case-control study.
Ribosomal intergenic spacer analysis (RISA) was conducted to identify unique DNA
bands in tissues from patients with CD and UC that did not appear in controls.
RESULTS: RISA followed by DNA sequencing identified unique bands in biopsy
specimens from patients with IBD that were classified as Escherichia coli.
Targeted culture showed a significantly (p<0.05) higher number of
Enterobacteriaceae in specimens from patients with IBD. The B2+D phylogenetic
group, serine protease autotransporters (SPATE) and adherence factors were more
likely to be associated with tissues from patients with UC and CD than with
controls. CONCLUSIONS: The abundance of Enterobacteriaceae is 3-4 logs higher in
tissues of patients with IBD and the B2+D phylogenetic groups are more prevalent
in patients with UC and CD. The B2+D phylogenetic groups are associated with
SPATE and adherence factors and may have a significant role in disease aetiology.
PMID- 17028129
TI - Ultrasonic storage modulus as a novel parameter for analyzing protein-protein
interactions in high protein concentration solutions: correlation with static and
dynamic light scattering measurements.
AB - The purpose of this work was to establish ultrasonic storage modulus (G') as a
novel parameter for characterizing protein-protein interactions (PPI) in high
concentration protein solutions. Using an indigenously developed ultrasonic shear
rheometer, G' for 20-120 mg/ml solutions of a monoclonal antibody (IgG(2)),
between pH 3.0 and 9.0 at 4 mM ionic strength, was measured at frequency of 10
MHz. Our understanding of ultrasonic rheology indicated decrease in repulsive and
increase in attractive PPI with increasing solution pH. To confirm this behavior,
dynamic (DLS) and static (SLS) light scattering measurements were conducted in
dilute solutions. Due to technical limitations, light scattering measurements
could not be conducted in concentrated solutions. Mutual-diffusion coefficient,
measured by DLS, increased with IgG(2) concentration at pH 4.0 and this trend
reversed as pH was increased to 9.0. Second virial coefficient, measured by SLS,
decreased with increasing pH. These observations were consistent with the nature
of PPI understood from G' measurements. Ultrasonic rheology, DLS, and SLS
measurements were also conducted under conditions of increased ionic strength.
The consistency between rheology and light scattering analysis under various
solution conditions established the utility of ultrasonic G' measurements as a
novel tool for analyzing PPI in high protein concentration systems.
PMID- 17028131
TI - Time-dependent DNA condensation induced by amyloid beta-peptide.
AB - The major protein component of the amyloid deposition in Alzheimer's disease is a
39-43 residue peptide, amyloid beta (Abeta). Abeta is toxic to neurons, although
the mechanism of neurodegeneration is uncertain. Evidence exists for non-B DNA
conformation in the hippocampus of Alzheimer's disease brains, and Abeta was
reportedly able to transform DNA conformation in vitro. In this study, we found
that DNA conformation was altered in the presence of Abeta, and Abeta induced DNA
condensation in a time-dependent manner. Furthermore, Abeta sheets, serving as
condensation nuclei, were crucial for DNA condensation, and Cu(2+) and Zn(2+)
ions inhibited Abeta sheet-induced DNA condensation. Our results suggest DNA
condensation as a mechanism of Abeta toxicity.
PMID- 17028130
TI - Protein crystallography under xenon and nitrous oxide pressure: comparison with
in vivo pharmacology studies and implications for the mechanism of inhaled
anesthetic action.
AB - In contrast with most inhalational anesthetics, the anesthetic gases xenon (Xe)
and nitrous oxide (N(2)O) act by blocking the N-methyl-d-aspartate (NMDA)
receptor. Using x-ray crystallography, we examined the binding characteristics of
these two gases on two soluble proteins as structural models: urate oxidase,
which is a prototype of a variety of intracellular globular proteins, and annexin
V, which has structural and functional characteristics that allow it to be
considered as a prototype for the NMDA receptor. The structure of these proteins
complexed with Xe and N(2)O were determined. One N(2)O molecule or one Xe atom
binds to the same main site in both proteins. A second subsite is observed for
N(2)O in each case. The gas-binding sites are always hydrophobic flexible
cavities buried within the monomer. Comparison of the effects of Xe and N(2)O on
urate oxidase and annexin V reveals an interesting relationship with the in vivo
pharmacological effects of these gases, the ratio of the gas-binding sites'
volume expansion and the ratio of the narcotic potency being similar. Given these
data, we propose that alterations of cytosolic globular protein functions by
general anesthetics would be responsible for the early stages of anesthesia such
as amnesia and hypnosis and that additional alterations of ion-channel membrane
receptor functions are required for deeper effects that progress to "surgical"
anesthesia.
PMID- 17028132
TI - Mechanism of the difference in the binding affinity of E. coli tRNAGln to
glutaminyl-tRNA synthetase caused by noninterface nucleotides in variable loop.
AB - Aminoacyl-tRNA synthetases (ARSs) distinguish their cognate tRNAs from many other
kinds of tRNAs, despite the very similar tertiary structures of tRNAs. Many
researchers have supported the view that this recognition is achieved by
intermolecular interactions between tRNA and ARS. However, one of the aptamers of
Escherichia coli glutamine specific tRNA, var-AGGU, has a higher affinity to ARS
than the wild-type, although the sequence difference only lies in the variable
loop located on the opposite side of the binding interface with ARS. To
understand the reason for the difference in affinity, we did molecular dynamics
simulations on tRNAs and their complexes with ARS. We calculated the enthalpic
and entropic contributions to the binding free energy with the molecular
mechanics-Poisson-Boltzmann/surface area method and found that the entropic
difference plays an important role in the difference in binding free energies.
During the molecular dynamics simulations, dynamic rearrangements of hydrogen
bonds occurred in the tertiary core region of the wild-type tRNA, whereas they
were not observed in the free var-AGGU simulation. Since the internal mobility
was suppressed upon complex formation with ARS, the entropy loss in the wild-type
was larger than that of the aptamer. We therefore concluded that the sequence
difference in the variable loop caused the difference in the internal mobility of
the tertiary core region tRNAs and led to the difference in the affinity to ARS
through the entropy term.
PMID- 17028133
TI - Growth dynamics of domains in ternary fluid vesicles.
AB - We have studied the growth dynamics of domains on ternary fluid vesicles composed
of saturated (dipalmitoylphosphatidylcholine), unsaturated
(dioleoylphosphatidylcholine) phosphatidylcholine lipids, and cholesterol using a
fluorescence microscopy. The domain coarsening processes are classified into two
types: normal coarsening and trapped coarsening. For the normal coarsening, the
domains having flat circular shape grow in a diffusion-and-coalescence manner and
phenomenologically the mean size grows as a power law of approximately t(2/3).
The observed growth law is not described by a two-dimensional diffusion-and
coalescence growth mechanism following the Saffman and Delbruck theory, which may
originate from the two-body hydrodynamic interactions between domains. For
trapped coarsening, on the other hand, the domain coarsening is suppressed at a
certain domain size because the repulsive interdomain interactions obstruct the
coalescence of domains. The two-color imaging of the trapped domains reveals that
the repulsive interactions are induced by the budding of domains. The model free
energy consisting of the bending energy of domains, the bending energy of matrix,
the line energy of domain boundary, and the translation energy of domains can
describe the observed trapped coarsening. The trapping of domains is caused by
the coupling between the phase separation and the membrane elasticity under the
incompressibility constraint.
PMID- 17028134
TI - Microtubule protofilament number is modulated in a stepwise fashion by the charge
density of an enveloping layer.
AB - Microtubules are able to adjust their protofilament (PF) number and, as a
consequence, their dynamics and function, to the assembly conditions and presence
of cofactors. However, the principle behind such variations is poorly understood.
Using synchrotron x-ray scattering and transmission electron microscopy, we
studied how charged membranes, which under certain conditions can envelop pre
assembled MTs, regulate the PF number of those MTs. We show that the mean PF
number, , is modulated primarily by the charge density of the membranes.
decreases in a stepwise fashion with increasing membrane charge density. does
not depend on the membrane-protein stoichiometry or the solution ionic strength.
We studied the effect of taxol and found that increases logarithmically with
taxol/tubulin stoichiometry. We present a theoretical model, which by balancing
the electrostatic and elastic interactions in the system accounts for the trends
in our findings and reveals an effective MT bending stiffness of order 10-100
k(B)T/nm, associated with the observed changes in PF number.
PMID- 17028135
TI - Collagen fibrils: nanoscale ropes.
AB - The formation of collagen fibrils from staggered repeats of individual molecules
has become "accepted" wisdom. However, for over thirty years now, such a model
has failed to resolve several structural and functional questions. In a novel
approach, it was found, using atomic force microscopy, that tendon collagen
fibrils are composed of subcomponents in a spiral disposition-that is, their
structure is similar to that of macroscale ropes. Consequently, this arrangement
was modeled and confirmed using elastic rod theory. This work provides new
insight into collagen fibril structure and will have wide application-from the
design of scaffolds for tissue engineering and a better understanding of
pathogenesis of diseases of bone and tendon, to the conservation of irreplaceable
parchment-based museum exhibits.
PMID- 17028136
TI - Possible pathway for ubiquinone shuttling in Rhodospirillum rubrum revealed by
molecular dynamics simulation.
AB - In the last decade, the structures of many components of the photosynthetic
apparatus of purple bacteria, as well as the mutual organization of these
components within the purple membrane, were resolved. One key question that
emerged concerned the assembly of the core complex consisting of the reaction
center (RC) and the light-harvesting 1 (LH1) complex. In some species, like
Rhodobacter sphaeroides, the ring-shaped LH1 complex was found to be open,
whereas other species, like Rhodospirillum rubrum, have a closed ring surrounding
the reaction center. This poses the question of how the ubiquinone molecule that
transports electrons and protons from the RC to the cytochrome bc(1) complex
overcomes the apparent barrier of the LH1 ring. In this study, we investigated
how, in the case of a closed LH1 ring, the ubiquinone molecule diffuses through
the LH1 ring. For this purpose, the LH1 structure of R. rubrum was modeled and
the potential of mean force along the diffusion pathway through the LH1 was
determined by steered molecular-dynamics simulations. The potential was
reconstructed using the fluctuation theorem in combination with the stiff spring
approximation. An upper limit for the mean first-passage time for diffusion of
ubiquinone through the LH1 ring, based on a worst-case scenario potential, was
calculated as approximately 8 x 10(-3) s, which is still in agreement with known
turnover rates of RC and RC-LH1 complexes in the range of approximately 1000 Hz.
PMID- 17028137
TI - A structural origin of latency relaxation in frog skeletal muscle.
AB - A time-resolved x-ray diffraction study at a time resolution of 0.53 ms was made
to investigate the structural origin of latency relaxation (LR) in frog skeletal
muscle. Intensity and spacing measurements were made on meridional reflections
from the Ca-binding protein troponin and the thick filament and on layer lines
from the thin filament. At 16 degrees C, the intensity and spacing of all
reflections started to change at 4 ms, simultaneously with the LR. At 0 degrees
C, the intensity of the troponin reflection and the layer lines from the thin
filament and the spacing of the 14.3-nm myosin meridional reflection, but not the
spacing of other myosin meridional reflections, began to change at approximately
15 ms, when the LR also started. Intensity of myosin-based reflections started to
change later. When the muscle was stretched to non-overlap length, the intensity
and spacing changes of the myosin reflections disappeared. The simultaneous
spacing change of the 14.3-nm myosin meridional reflection with the LR suggests
that detachment of myosin heads that are bound to actin in the resting muscle is
the cause of the LR.
PMID- 17028138
TI - Cholesterol sulfate and Ca(2+) modulate the mixing properties of lipids in
stratum corneum model mixtures.
AB - The influence of cholesterol sulfate (CS) and calcium on the phase behavior of
lipid mixtures mimicking the stratum corneum (SC) lipids was examined using
vibrational spectroscopy. Raman microspectrocopy showed that equimolar mixtures
of ceramide, palmitic acid, and cholesterol underwent a phase transition in
which, at low temperatures, lipids formed mainly a mosaic of microcrystalline
phase-separated domains, and above 45 degrees C, a more fluid and disordered
phase in which the three lipid species were more miscible. In the presence of
Ca(2+), there was the formation of fatty acid-Ca(2+) complexes that led to
domains stable on heating. Consequently, these lipid mixtures remained
heterogeneous, and the fatty acid molecules were not extensively involved in the
formation of the fluid lipid phase, which included mainly ceramide and
cholesterol. However, the presence of CS displaced the association site of Ca(2+)
ions and inhibited the formation of domains formed by the fatty acid molecules
complexed with Ca(2+) ions. This work reveals that CS and Ca(2+) modulate the
lipid mixing properties and the lipid order in SC lipid models. The balance in
the equilibria involving Ca(2+), CS, and fatty acids is proposed to have an
impact on the organization and the function of the epidermis.
PMID- 17028139
TI - Dynamics of the nucleotide pocket of myosin measured by spin-labeled nucleotides.
AB - We have used electron paramagnetic probes attached to the ribose of ATP (SL-ATP)
to monitor conformational changes in the nucleotide pocket of myosin. Spectra for
analogs bound to myosin in the absence of actin showed a high degree of
immobilization, indicating a closed nucleotide pocket. In the Actin.Myosin.SL
AMPPNP, Actin.Myosin.SL-ADP.BeF(3), and Actin.Myosin.SL-ADP.AlF(4) complexes,
which mimic weakly binding states near the beginning of the power stroke, the
nucleotide pocket remained closed. The spectra of the strongly bound
Actin.Myosin.SL-ADP complex consisted of two components, one similar to the
closed pocket and one with increased probe mobility, indicating a more open
pocket, The temperature dependence of the spectra showed that the two
conformations of the nucleotide pocket were in equilibrium, with the open
conformation more favorable at higher temperatures. These results, which show
that opening of the pocket occurs only in the strongly bound states, appear
reasonable, as this would tend to keep ADP bound until the end of the power
stroke. This conclusion also suggests that force is initially generated by a
myosin with a closed nucleotide pocket.
PMID- 17028140
TI - Role of pairwise interactions between M1 and M2 domains of the nicotinic receptor
in channel gating.
AB - The adult form of the nicotinic acetylcholine receptor (AChR) consists of five
subunits (alpha(2)betaepsilondelta), each having four transmembrane domains (M1
M4). The atomic model of the nicotinic acetylcholine receptor shows that the pore
lining M2 domains make no extensive contacts with the rest of the transmembrane
domains. However, there are several sites where close appositions between
segments occur. It has been suggested that the pair alphaM1-F15' and alphaM2-L11'
is one of the potential interactions between segments. To determine
experimentally if these residues are interacting and to explore if this
interhelical interaction is essential for channel gating, we combined mutagenesis
with single-channel kinetic analysis. Mutations in alphaM1-F15' lead to profound
changes in the opening rate and slighter changes in the closing rate. Channel
gating is impaired as the volume of the residue increases. Rate-equilibrium
linear free-energy relationship analysis reveals an approximately 70% open-state
like environment for alphaM1-F15' at the transition state of the gating reaction,
suggesting that it moves early during the gating process. Replacing the residue
at alphaM1-15' by that at alphaM2-11' and vice versa profoundly alters gating,
but the combination of the two mutations restores gating to near normal,
indicating that alphaM1-F15' and alphaM2-L11' are interchangeable. Double-mutant
cycle analysis shows that these residues are energetically coupled. Thus, the
interaction between M1 and M2 plays a key role in channel gating.
PMID- 17028141
TI - Composition effect on peptide interaction with lipids and bacteria: variants of
C3a peptide CNY21.
AB - The effect of peptide hydrophobicity and charge on peptide interaction with model
lipid bilayers was investigated for the C3a-derived peptide CNY21 by fluorescence
spectroscopy, circular dichroism, ellipsometry, z-potential, and photon
correlation spectroscopy measurements. For both zwitterionic and anionic
liposomes, the membrane-disruptive potency for CNY21 variants increased with
increasing net positive charge and mean hydrophobicity and was completely lost on
elimination of all peptide positive charges. Analogous effects of elimination of
the peptide positive net charge in particular were found regarding bacteria
killing for both Pseudomonas aeruginosa and Bacillus subtilis. The peptides,
characterized by moderate helix content both in buffer and when attached to the
liposomes, displayed high adsorption for the net positively charged peptide
variants, whereas adsorption was non-measurable for the uncharged peptide. That
electrostatically driven adsorption represents the main driving force for
membrane disruption in lipid systems was also demonstrated by a drastic reduction
in both liposome leakage and peptide adsorption with increasing ionic strength,
and this salt inactivation can be partly avoided by increasing the peptide
hydrophobicity. This increased electrolyte resistance translates also to a higher
antibacterial effect for the hydrophobically modified variant at high salt
concentration. Overall, our findings demonstrate the importance of the peptide
adsorption and resulting peptide interfacial density for membrane-disruptive
effects of these peptides.
PMID- 17028142
TI - Mechanical unfolding of RNA: from hairpins to structures with internal
multiloops.
AB - Mechanical unfolding of RNA structures, ranging from hairpins to ribozymes, using
laser optical tweezer experiments have begun to reveal the features of the energy
landscape that cannot be easily explored using conventional experiments. Upon
application of constant force (f), RNA hairpins undergo cooperative transitions
from folded to unfolded states whereas subdomains of ribozymes unravel one at a
time. Here, we use a self-organized polymer model and Brownian dynamics
simulations to probe mechanical unfolding at constant force and constant-loading
rate of four RNA structures of varying complexity. For simple hairpins, such as
P5GA, application of constant force or constant loading rate results in bistable
cooperative transitions between folded and unfolded states without populating any
intermediates. The transition state location (DeltaxFTS) changes dramatically as
the loading rate is varied. At loading rates comparable to those used in laser
optical tweezer experiments, the hairpin is plastic, with DeltaxFTS being midway
between folded and unfolded states; whereas at high loading rates, DeltaxFTS
moves close to the folded state, i.e., RNA is brittle. For the 29-nucleotide TAR
RNA with the three-nucleotide bulge, unfolding occurs in a nearly two-state
manner with an occasional pause in a high free energy metastable state. Forced
unfolding of the 55 nucleotides of the Hepatitis IRES domain IIa, which has a
distorted L-shaped structure, results in well-populated stable intermediates. The
most stable force-stabilized intermediate represents straightening of the L
shaped structure. For these structures, the unfolding pathways can be predicted
using the contact map of the native structures. Unfolding of a RNA motif with
internal multiloop, namely, the 109-nucleotide prohead RNA that is part of the 29
DNA packaging motor, at constant value of rf occurs with three distinct rips that
represent unraveling of the paired helices. The rips represent kinetic barriers
to unfolding. Our work shows 1), the response of RNA to force is largely
determined by the native structure; and 2), only by probing mechanical unfolding
over a wide range of forces can the underlying energy landscape be fully
explored.
PMID- 17028144
TI - Protein phase diagrams II: nonideal behavior of biochemical reactions in the
presence of osmolytes.
AB - In the age of biochemical systems biology, proteomics, and high throughput
methods, the thermodynamic quantification of cytoplasmatic reaction networks
comes into reach of the current generation of scientists. What is needed to
efficiently extract the relevant information from the raw data is a robust tool
for evaluating the number and stoichiometry of all observed reactions while
providing a good estimate of the thermodynamic parameters that determine the
molecular behavior. The recently developed phase-diagram method, strictly
speaking a graphical representation of linkage or Maxwell Relations, offers such
capabilities. Here, we extend the phase diagram method to nonideal conditions.
For the sake of simplicity, we choose as an example a reaction system involving
the protein RNase A, its inhibitor CMP, the osmolyte urea, and water. We
investigate this system as a function of the concentrations of inhibitor and
osmolyte at different temperatures ranging from 280 K to 340 K. The most
interesting finding is that the protein-inhibitor binding equilibrium depends
strongly on the urea concentration--by orders-of-magnitude more than expected
from urea-protein interaction alone. Moreover, the m-value of ligand binding is
strongly concentration-dependent, which is highly unusual. It is concluded that
the interaction between small molecules like urea and CMP can significantly
contribute to cytoplasmic nonideality. Such a finding is highly significant
because of its impact on renal tissue where high concentrations of cosolutes
occur regularly.
PMID- 17028143
TI - Novel lipid transfer property of two mitochondrial proteins that bridge the inner
and outer membranes.
AB - This study provides evidence of a novel function for mitochondrial creatine
kinase (MtCK) and nucleoside diphosphate kinase (NDPK-D). Both are basic
peripheral membrane proteins with symmetrical homo-oligomeric structure, which in
the case of MtCK was already shown to allow crossbridging of lipid bilayers.
Here, different lipid dilution assays clearly demonstrate that both kinases also
facilitate lipid transfer from one bilayer to another. Lipid transfer occurs
between liposomes mimicking the lipid composition of mitochondrial contact sites,
containing 30 mol % cardiolipin, but transfer does not occur when cardiolipin is
replaced by phosphatidylglycerol. Ubiquitous MtCK, but not NDPK-D, shows some
specificity in the nature of the lipids transferred and it is not active with
phosphatidylcholine alone. MtCK can undergo reversible oligomerization between
dimeric and octameric forms, but only the octamer can bridge membranes and
promote lipid transfer. Cytochrome c, another basic mitochondrial protein known
to bind to anionic membranes but not crosslinking them, is also incapable of
promoting lipid transfer. The lipid transfer process does not involve vesicle
fusion or loss of the internal contents of the liposomes.
PMID- 17028145
TI - Contour length and refolding rate of a small protein controlled by engineered
disulfide bonds.
AB - The introduction of disulfide bonds into proteins creates additional mechanical
barriers and limits the unfolded contour length (i.e., the maximal extension)
measured by single-molecule force spectroscopy. Here, we engineer single
disulfide bonds into four different locations of the human cardiac titin module
(I27) to control the contour length while keeping the distance to the transition
state unchanged. This enables the study of several biologically important
parameters. First, we are able to precisely determine the end-to-end length of
the transition state before unfolding (53 Angstrom), which is longer than the end
to-end length of the protein obtained from NMR spectroscopy (43 Angstrom).
Second, the measured contour length per amino acid from five different methods
(4.0 +/- 0.2 Angstrom) is longer than the end-to-end length obtained from the
crystal structure (3.6 Angstrom). Our measurement of the contour length takes
into account all the internal degrees of freedom of the polypeptide chain,
whereas crystallography measures the end-to-end length within the "frozen"
protein structure. Furthermore, the control of contour length and therefore the
number of amino acids unraveled before reaching the disulfide bond (n)
facilitates the test of the chain length dependence on the folding time (tau(F)).
We find that both a power law scaling tau(F) lambda n(lambda) with lambda = 4.4,
and an exponential scaling with n(0.6) fit the data range, in support of
different protein-folding scenarios.
PMID- 17028146
TI - Transport governs flow-enhanced cell tethering through L-selectin at threshold
shear.
AB - Flow-enhanced cell adhesion is a counterintuitive phenomenon that has been
observed in several biological systems. Flow augments L-selectin-dependent
adhesion by increasing the initial tethering of leukocytes to vascular surfaces
and by strengthening their subsequent rolling interactions. Tethering or rolling
might be influenced by physical factors that affect the formation or dissociation
of selectin-ligand bonds. We recently demonstrated that flow enhanced rolling of
L-selectin-bearing microspheres or neutrophils on P-selectin glycoprotein ligand
1 by force decreased bond dissociation. Here, we show that flow augmented
tethering of these microspheres or cells to P-selectin glycoprotein ligand-1 by
three transport mechanisms that increased bond formation: sliding of the sphere
bottom on the surface, Brownian motion, and molecular diffusion. These results
elucidate the mechanisms for flow-enhanced tethering through L-selectin.
PMID- 17028147
TI - Anesthesia, analgesia, and euphoria.
PMID- 17028148
TI - Molecular interactions between the specialist herbivore Manduca sexta
(Lepidoptera, Sphingidae) and its natural host Nicotiana attenuata. VII. Changes
in the plant's proteome.
AB - When Manduca sexta attacks Nicotiana attenuata, fatty acid-amino acid conjugates
(FACs) in the larvae's oral secretions (OS) are introduced into feeding wounds.
These FACs trigger a transcriptional response that is similar to the response
induced by insect damage. Using two-dimensional gel electrophoresis, matrix
assisted laser desorption ionization-time of flight, and liquid chromatography
tandem mass spectrometry, we characterized the proteins in phenolic extracts and
in a nuclear fraction of leaves elicited by larval attack, and/or in leaves
wounded and treated with OS, FAC-free OS, and synthetic FACs. Phenolic extracts
yielded approximately 600 protein spots, many of which were altered by
elicitation, whereas nuclear protein fractions yielded approximately 100 spots,
most of which were unchanged by elicitation. Reproducible elicitor-induced
changes in 90 spots were characterized. In general, proteins that increased were
involved in primary metabolism, defense, and transcriptional and translational
regulation; those that decreased were involved in photosynthesis. Like the
transcriptional defense responses, proteomic changes were strongly elicited by
the FACs in OS. A semiquantitative reverse transcription-PCR approach based on
peptide sequences was used to compare transcript and protein accumulation
patterns for 17 candidate proteins. In six cases the patterns of elicited
transcript accumulation were consistent with those of elicited protein
accumulation. Functional analysis of one of the identified proteins involved in
photosynthesis, RuBPCase activase, was accomplished by virus-induced gene
silencing. Plants with decreased levels of RuBPCase activase protein had reduced
photosynthetic rates and RuBPCase activity, and less biomass, responses
consistent with those of herbivore-attacked plants. We conclude that the response
of the plant's proteome to herbivore elicitation is complex, and integrated
transcriptome-proteome-metabolome analysis is required to fully understand this
ubiquitous ecological interaction.
PMID- 17028149
TI - Proteomic analysis of seed dormancy in Arabidopsis.
AB - The mechanisms controlling seed dormancy in Arabidopsis (Arabidopsis thaliana)
have been characterized by proteomics using the dormant (D) accession Cvi
originating from the Cape Verde Islands. Comparative studies carried out with
freshly harvested dormant and after-ripened non-dormant (ND) seeds revealed a
specific differential accumulation of 32 proteins. The data suggested that
proteins associated with metabolic functions potentially involved in germination
can accumulate during after-ripening in the dry state leading to dormancy
release. Exogenous application of abscisic acid (ABA) to ND seeds strongly
impeded their germination, which physiologically mimicked the behavior of D
imbibed seeds. This application resulted in an alteration of the accumulation
pattern of 71 proteins. There was a strong down-accumulation of a major part
(90%) of these proteins, which were involved mainly in energetic and protein
metabolisms. This feature suggested that exogenous ABA triggers proteolytic
mechanisms in imbibed seeds. An analysis of de novo protein synthesis by two
dimensional gel electrophoresis in the presence of [(35)S]-methionine disclosed
that exogenous ABA does not impede protein biosynthesis during imbibition.
Furthermore, imbibed D seeds proved competent for de novo protein synthesis,
demonstrating that impediment of protein translation was not the cause of the
observed block of seed germination. However, the two-dimensional protein profiles
were markedly different from those obtained with the ND seeds imbibed in ABA.
Altogether, the data showed that the mechanisms blocking germination of the ND
seeds by ABA application are different from those preventing germination of the D
seeds imbibed in basal medium.
PMID- 17028150
TI - Physiological characterization of two genes for Na+ exclusion in durum wheat,
Nax1 and Nax2.
AB - Durum wheat (Triticum turgidum L. subsp. durum Desf.) Line 149 contains two novel
major genes for excluding Na(+) from leaf blades, named Nax1 and Nax2. The genes
were separated into families containing a single gene and near-isogenic
homozygous lines were selected. Lines containing either Nax1 or Nax2 had lower
rates of Na(+) transport from roots to shoots than their near-isogenic pairs due
to lower rates of net loading of the xylem, not to lower rates of net uptake from
the soil or higher rates of retranslocation in the phloem. Nax1 and Nax2 lines
also had higher rates of K(+) transport from root to shoot, resulting in an
enhanced discrimination of K(+) over Na(+). Lines containing Nax1 differed from
those containing Nax2 by unloading Na(+) from the xylem as it entered the shoot
so that Na(+) was retained in the base of the leaf, leading to a high sheath to
blade ratio of Na(+) concentration. Gradients in tissue concentrations of Na(+)
along the leaf suggested that Na(+) was continually removed from the xylem. The
Nax2 line did not retain Na(+) in the base of the leaf, suggesting that it
functioned only in the root. The Nax2 gene therefore has a similar function to
Kna1 in bread wheat (Triticum aestivum).
PMID- 17028151
TI - Modifications to the Arabidopsis defense proteome occur prior to significant
transcriptional change in response to inoculation with Pseudomonas syringae.
AB - Alterations in the proteome of Arabidopsis (Arabidopsis thaliana) leaves during
responses to challenge by Pseudomonas syringae pv tomato DC3000 were analyzed
using two-dimensional gel electrophoresis. Protein changes characteristic of the
establishment of disease, basal resistance, and resistance-gene-mediated
resistance were examined by comparing responses to DC3000, a hrp mutant, and
DC3000 expressing avrRpm1, respectively. The abundance of each protein identified
was compared with that of selected transcripts obtained from comparable GeneChip
experiments. We report changes in three subcellular fractions: total soluble
protein, chloroplast enriched, and mitochondria enriched over four time points
(1.5-6 h after inoculation). In total, 73 differential spots representing 52
unique proteins were successfully identified. Many of the changes in protein spot
density occurred before significant transcriptional reprogramming was evident
between treatments. The high proportion of proteins represented by more than one
spot indicated that many of the changes to the proteome can be attributed to
posttranscriptional modifications. Proteins found to show significant change
after bacterial challenge are representative of two main functional groups:
defense-related antioxidants and metabolic enzymes. Significant changes to
photosystem II and to components of the mitochondrial permeability transition
were also identified. Rapid communication between organelles and regulation of
primary metabolism through redox-mediated signaling are supported by our data.
PMID- 17028152
TI - Large-scale cis-element detection by analysis of correlated expression and
sequence conservation between Arabidopsis and Brassica oleracea.
AB - The rapidly increasing amount of plant genomic sequences allows for the detection
of cis-elements through comparative methods. In addition, large-scale gene
expression data for Arabidopsis (Arabidopsis thaliana) have recently become
available. Coexpression and evolutionarily conserved sequences are criteria
widely used to identify shared cis-regulatory elements. In our study, we employ
an integrated approach to combine two sources of information, coexpression and
sequence conservation. Best-candidate orthologous promoter sequences were
identified by a bidirectional best blast hit strategy in genome survey sequences
from Brassica oleracea. The analysis of 779 microarrays from 81 different
experiments provided detailed expression information for Arabidopsis genes
coexpressed in multiple tissues and under various conditions and developmental
stages. We discovered candidate transcription factor binding sites in 64% of the
Arabidopsis genes analyzed. Among them, we detected experimentally verified
binding sites and showed strong enrichment of shared cis-elements within
functionally related genes. This study demonstrates the value of partially
shotgun sequenced genomes and their combinatorial use with functional genomics
data to address complex questions in comparative genomics.
PMID- 17028153
TI - Differential operation of dual protochlorophyllide reductases for chlorophyll
biosynthesis in response to environmental oxygen levels in the cyanobacterium
Leptolyngbya boryana.
AB - Most oxygenic phototrophs, including cyanobacteria, have two structurally
unrelated protochlorophyllide (Pchlide) reductases in the penultimate step of
chlorophyll biosynthesis. One is light-dependent Pchlide reductase (LPOR) and the
other is dark-operative Pchlide reductase (DPOR), a nitrogenase-like enzyme
assumed to be sensitive to oxygen. Very few studies have been conducted on how
oxygen-sensitive DPOR operates in oxygenic phototrophic cells. Here, we report
that anaerobic conditions are required for DPOR to compensate for the loss of
LPOR in cyanobacterial cells. An LPOR-lacking mutant of the cyanobacterium
Leptolyngbya boryana (formerly Plectonema boryanum) failed to grow in high light
conditions and this phenotype was overcome by cultivating it under anaerobic
conditions (2% CO(2)/N(2)). The critical oxygen level enabling the mutant to grow
in high light was determined to be 3% (v/v). Oxygen-sensitive Pchlide reduction
activity was successfully detected as DPOR activity in cell-free extracts of
anaerobically grown mutants, whereas activity was undetectable in the wild type.
The content of two DPOR subunits, ChlL and ChlN, was significantly increased in
mutant cells compared with wild type. This suggests that the increase in subunits
stimulates the DPOR activity that is protected efficiently from oxygen by
anaerobic environments, resulting in complementation of the loss of LPOR. These
results provide important concepts for understanding how dual Pchlide reductases
operate differentially in oxygenic photosynthetic cells grown under natural
environments where oxygen levels undergo dynamic changes. The evolutionary
implications of the coexistence of two Pchlide reductases are discussed.
PMID- 17028154
TI - AKINbetagamma contributes to SnRK1 heterotrimeric complexes and interacts with
two proteins implicated in plant pathogen resistance through its KIS/GBD
sequence.
AB - The sucrose nonfermenting-1 protein kinase (SNF1)/AMP-activated protein kinase
subfamily plays a central role in metabolic responses to nutritional and
environmental stresses. In yeast (Saccharomyces cerevisiae) and mammals, the beta
and gamma-noncatalytic subunits are implicated in substrate specificity and
subcellular localization, respectively, and regulation of the kinase activity.
The atypical betagamma-subunit has been previously described in maize (Zea mays),
presenting at its N-terminal end a sequence related to the KIS (kinase
interacting sequence) domain specific to the beta-subunits (Lumbreras et al.,
2001). The existence of two components, SNF1-related protein kinase (SnRK1)
complexes containing the betagamma-subunit and one SnRK1 kinase, had been
proposed. In this work, we show that, despite its unusual features, the
Arabidopsis (Arabidopsis thaliana) homolog AKINbetagamma clearly interacts with
AKINbeta-subunits in vitro and in vivo, suggesting its involvement in
heterotrimeric complexes located in both cytoplasm and nucleus. Unexpectedly, a
transcriptional analysis of AKINbetagamma gene expression highlighted the
implication of alternative splicing mechanisms in the regulation of AKINbetagamma
expression. A two-hybrid screen performed with AKINbetagamma as bait, together
with in planta bimolecular fluorescence complementation experiments, suggests the
existence of interactions in the cytosol between AKINbetagamma and two leucine
rich repeats related to pathogen resistance proteins. Interestingly, this
interaction occurs through the truncated KIS domain that corresponds exactly to a
GBD (glycogen-binding domain) recently described in mammals and yeast. A
phylogenetic study suggests that AKINbetagamma-related proteins are restricted to
the plant kingdom. Altogether, these data suggest the existence of plant-specific
SnRK1 trimeric complexes putatively involved in a plant-specific function such as
plant-pathogen interactions.
PMID- 17028155
TI - The BnALMT1 and BnALMT2 genes from rape encode aluminum-activated malate
transporters that enhance the aluminum resistance of plant cells.
AB - The release of organic anions from roots can protect plants from aluminum (Al)
toxicity and help them overcome phosphorus (P) deficiency. Our previous findings
showed that Al treatment induced malate and citrate efflux from rape (Brassica
napus) roots, and that P deficiency did not induce the efflux. Since this
response is similar to the malate efflux from wheat (Triticum aestivum) that is
controlled by the TaALMT1 gene, we investigated whether homologs of TaALMT1 are
present in rape and whether they are involved in the release of organic anions.
We isolated two TaALMT1 homologs from rape designated BnALMT1 and BnALMT2 (B.
napus Al-activated malate transporter). The expression of these genes was induced
in roots, but not shoots, by Al treatment but P deficiency had no effect. Several
other cations (lanthanum, ytterbium, and erbium) also increased BnALMT1 and
BnALMT2 expression in the roots. The function of the BnALMT1 and BnALMT2 proteins
was investigated by heterologous expression in cultured tobacco (Nicotiana
tabacum) cells and in Xenopus laevis oocytes. Both transfection systems showed an
enhanced capacity for malate efflux but not citrate efflux, when exposed to Al.
Smaller malate fluxes were also activated by ytterbium and erbium treatment.
Transgenic tobacco cells grew significantly better than control cells following
an 18 h treatment with Al, indicating that the expression of BnALMT1 and BnALMT2
increased the resistance of these plant cells to Al stress. This report
demonstrates that homologs of the TaALMT1 gene from wheat perform similar
functions in other species.
PMID- 17028156
TI - Embelin, an inhibitor of X chromosome-linked inhibitor-of-apoptosis protein,
blocks nuclear factor-kappaB (NF-kappaB) signaling pathway leading to suppression
of NF-kappaB-regulated antiapoptotic and metastatic gene products.
AB - Identifying the active chemical ingredients of ancient medicines and the
molecular targets of those ingredients is an attractive therapeutic objective.
Embelin, identified primarily from the Embelia ribes plant, is one such compound
shown to exhibit chemopreventive, anti-inflammatory, and apoptotic activities
through an unknown mechanism. Because nuclear factor-kappaB (NF-kappaB) regulates
several genes associated with inflammation, proliferation, carcinogenesis, and
apoptosis, we postulated that embelin might mediate its activity through
modulation of NF-kappaB activation. We found that embelin inhibited tumor
necrosis factor (TNF) alpha-induced NF-kappaB activation. Both inducible and
constitutive NF-kappaB activation were abrogated by embelin. In addition, NF
kappaB activated by diverse stimuli such as interleukin-1beta,
lipopolysaccharide, phorbol myristate acetate, okadaic acid, hydrogen peroxide,
and cigarette smoke condensate also was suppressed. We found that embelin
inhibited sequentially the TNFalpha-induced activation of the inhibitory subunit
of NF-kappaBalpha (IkappaBalpha) kinase, IkappaBalpha phosphorylation,
IkappaBalpha degradation, and p65 phosphorylation and nuclear translocation.
Embelin also suppressed NF-kappaB-dependent reporter gene transcription induced
by TNFalpha, TNF receptor-1 (TNFR1), TNFR1-associated death domain protein, TNFR
associated factor-2, NF-kappaB-inducing kinase, and IkappaBalpha kinase but not
by p65. Furthermore, we found that embelin down-regulated gene products involved
in cell survival, proliferation, invasion, and metastasis of the tumor. This down
regulation was associated with enhanced apoptosis by cytokine and
chemotherapeutic agents. Together, our results indicate that embelin is a novel
NF-kappaB blocker and potential suppressor of tumorigenesis.
PMID- 17028157
TI - The positional influence of the helical geometry of the heteroduplex substrate on
human RNase H1 catalysis.
AB - In a companion study published in this issue (p. 83), we showed that chimeric
substrates containing 2'-methoxyethyl (MOE) nucleotides inhibited human RNase H1
activity. In this study, we prepared chimeric substrates containing a central DNA
region with flanking northern-biased MOE nucleotides hybridized to complementary
RNA. Conformationally biased and flexible modified nucleotides were positioned at
the junctions between the DNA and MOE residues of the chimeric substrates to
modulate the effects of the MOE residues on human RNase H1 activity. The strong
northern-biased locked-nucleic acid modification exacerbated the negative effects
of the MOE modifications resulting in slower human RNase H1 cleavage rates.
Enhanced cleavage rates were observed for the eastern-biased 2'-ara
fluorothymidine and bulge inducing N-methylthymidine modifications positioned at
the 5'-DNA/3'-MOE junction as well as the southern-biased 2'-methylthiothymidine
and conformationally flexible tetrafluoroindole (TFI) modifications positioned at
the 5'-MOE/3'-DNA junction. The heterocycle of the ribonucleotide opposing the
TFI deoxyribonucleotide had no effect on the human RNase H1 activity, whereas
nucleotide substitutions adjacent the TFI significantly affected the cleavage
rate. Mismatch base pair(s) exhibited similar effects on human RNase H1 activity
as the TFI modifications. The effects of the TFI modification and mismatch base
pair(s) on human RNase H1 activity were influenced by the position of the
modification relative to the nucleotides interacting with the catalytic site of
the enzyme rather than the juxtaposition of the modification to the MOE residues.
Finally, these results provide a method for enhancing the human RNase H1 activity
of chimeric antisense oligonucleotides (ASO) as well as the design of more potent
ASO drugs.
PMID- 17028158
TI - Human RNase H1 discriminates between subtle variations in the structure of the
heteroduplex substrate.
AB - In a previous study, we demonstrated that the sugar conformation and helical
geometry of the heteroduplex substrate at the catalytic site of human RNase H1
directs the selective recognition of the substrate by the enzyme (J Biol Chem
279: 36317-36326, 2004). In this study, we systematically introduced 2'
methoxyethoxy (MOE) nucleotides into the antisense oligodeoxyribonucleotide (ASO)
of the heteroduplex to alter the helical geometry of the substrate. The MOE
substitutions at the 3' and 5' poles of the ASO resulted in fewer cleavage sites
and slower cleavage rates compared with the unmodified substrates. Furthermore, a
greater reduction in cleavage activity was observed for MOE substitutions at the
5' pole of the ASO. The 3'- and 5'-most cleavage sites were positioned two and
four to five base pairs, respectively, from the nearest MOE residues, suggesting
a conformational transmission of the MOE/RNA helical geometry into the DNA/RNA
portion of the heteroduplex. Similar conformational transmission was observed for
Okazaki-like substrates containing deoxyribonucleotide substitutions at the 3'
pole of the oligoribonucleotide. Finally, the heteroduplex substrates exhibited
preferred cleavage sites that were cleaved 2- to 3-fold faster than other sites
in the substrate, and these sites exhibited the greatest influence on the initial
cleavage rates. The data presented here offer further insights into the role
substrate structure plays in directing human RNase H1 activity as well as the
design of effective ASOs.
PMID- 17028159
TI - The dietary isothiocyanate sulforaphane is an antagonist of the human steroid and
xenobiotic nuclear receptor.
AB - Sulforaphane (SFN) is a biologically active phytochemical found abundantly in
broccoli. SFN has been promoted as a putative chemopreventive agent to reduce
cancer, and most studies have associated its anti-cancer effects with the
induction of phase II xenobiotic metabolism enzymes via activation of the
Keap1/Nrf2 antioxidant response pathway. Interestingly, SFN can significantly
down-regulate cytochrome P450 3A4 (CYP3A4) expression in human primary
hepatocytes. CYP3A4 is responsible for the hepatic and intestinal metabolism of
numerous protoxicants, pharmaceutical compounds, and endogenous sterols. Among
the most important mediators of CYP3A4 expression is the nuclear hormone
receptor, steroid and xenobiotic receptor (SXR; also called "hPXR"). SXR
functions as a xenobiotic sensor to coordinately regulate xenobiotic metabolism
via transcriptional regulation of xenobiotic-detoxifying enzymes and
transporters. Here, we report that SFN is a specific antagonist of human SXR and
that it inhibits SXR-mediated induction of drug clearance. SFN can bind directly
to SXR, inhibit SXR coactivator recruitment, and efficiently repress SXR
activities. Furthermore, SFN inhibited SXR-mediated CYP3A4 expression and CYP3A4
catalyzed midazolam clearance in human primary hepatocytes. Thus, SFN is the
first identified naturally occurring antagonist for SXR (hPXR). Because induction
of CYP3A4 can result in adverse drug responses (e.g., lack of efficacy), which
are a major public health problem, this discovery could lead to the development
of important new therapeutic and dietary approaches to reduce the frequency of
undesirable inducer-drug interactions.
PMID- 17028160
TI - O2 delivery and redox state are determinants of compartment-specific reactive O2
species in myocardial reperfusion.
AB - Reperfusion of the ischemic myocardium leads to a burst of reactive O(2) species
(ROS), which is a primary determinant of postischemic myocardial dysfunction. We
tested the hypothesis that early O(2) delivery and the cellular redox state
modulate the initial myocardial ROS production at reperfusion. Isolated buffer
perfused rat hearts were loaded with the fluorophores dihydrofluorescein or
Amplex red to detect intracellular and extracellular ROS formation using surface
fluorometry at the left ventricular wall. Hearts were made globally ischemic for
20 min and then reperfused with either 95% or 20% O(2)-saturated perfusate. The
same protocol was repeated in hearts loaded with dihydrofluorescein and perfused
with either 20 or 5 mM glucose-buffered solution to determine relative changes in
NADH and FAD. Myocardial O(2) delivery during the first 5 min of reperfusion was
84.7 +/- 4.2 ml O(2)/min with 20% O(2)-saturated buffer and 354.4 +/- 22.8 ml
O(2)/min with 95% O(2) (n = 8/group, P < 0.001). The fluorescein signal
(intracellular ROS) was significantly increased in hearts reperfused with 95%
O(2) compared with 20% O(2). However, the resorufin signal (extracellular ROS)
was significantly increased with 20% O(2) compared with 95% O(2) during
reperfusion. Perfusion of hearts with 20 mM glucose reduced the (.)NADH during
ischemia (P < 0.001) and the (.)ROS at reperfusion (P < 0.001) compared with 5.5
mM-perfused glucose hearts. In conclusion, initial O(2) delivery to the ischemic
myocardium modulates a compartment-specific ROS response at reperfusion such that
high O(2) delivery promotes intracellular ROS and low O(2) delivery promotes
extracellular ROS. The redox state that develops during ischemia appears to be an
important precursor for reperfusion ROS production.
PMID- 17028161
TI - Validation of the wall motion score and myocardial performance indexes as novel
techniques to assess cardiac function in mice after myocardial infarction.
AB - The aim of this study was to determine the feasibility and accuracy of wall
motion score index (WMSI) and myocardial performance index (MPI) for measuring
regional and global left ventricular (LV) function with use of high-resolution
echocardiography after myocardial infarction (MI) in mice. In 48 mice, myocardial
infarction was induced by ligation in the middle of the left anterior descending
coronary artery. Echocardiography was performed under anesthesia at baseline and
1 mo after MI. WMSI was analyzed by a 16-segment model on short-axis views, and
wall motion was scored as 1 for normal, 2 for hypokinetic, 3 for akinetic, 4 for
dyskinetic, and 5 for aneurysmal. WMSI was calculated as the sum of scores
divided by the total number of segments. MPI was calculated on the basis of
isovolumetric contraction time (IVCT), isovolumetric relaxation time (IVRT), and
ejection time (ET): MPI = (IVCT + IVRT)/ET. We measured LV ejection fraction
(LVEF), end-systolic and end-diastolic volumes (ESV and EDV), fractional
shortening (FS), and infarct size (IS). LVEF at 4 wk after MI was reduced at 32.8
+/- 9.0%. Linear correlation analyses showed that WMSI (1.6 +/- 0.3) correlated
with LVEF (r = -0.84, P < 0.0005), FS (r = -0.43, P = 0.003), and IS (34.3 +/-
15.3%, r = 0.86, P < 0.0005). MPI (0.67 +/- 0.09) correlated with LVEF (r =
0.67, P < 0.0005) and IS (r = 0.72, P < 0.0005). MPI also correlated with mitral
inflow velocity (r = -0.68, P < 0.0005) and deceleration time (r = -0.42, P =
0.003). Stepwise regression analysis revealed that WMSI was independently
associated with IS. IS, FS, mitral inflow velocity, and deceleration time were
independent determinants of MPI. In conclusion, echocardiographic assessments of
WMSI and MPI in mice are feasible and correlate strongly with two-dimensional
measurement of LV function and IS. These novel parameters provide additional
noninvasive assessment of regional and global LV function in mice after MI.
PMID- 17028162
TI - Characterization and localization of Ac-SDKP receptor binding sites using 125I
labeled Hpp-Aca-SDKP in rat cardiac fibroblasts.
AB - We have shown that the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac
SDKP) inhibited endothelin-1 (ET-1)-induced cell proliferation and collagen
synthesis in cultured rat cardiac fibroblasts (CFs) and reduced left ventricle
collagen deposition in rats with aldosterone (salt)- and ANG II-induced
hypertension. However, it is not known whether these effects are mediated by
receptor binding sites specific for Ac-SDKP. We hypothesized that Ac-SDKP exerts
antifibrotic effects by binding to specific receptor sites in cultured rat CFs,
which mediate the inhibitory effects of Ac-SDKP on ET-1-stimulated collagen
synthesis. Ac-SDKP binding sites in rat CFs and hearts were characterized by a
specific radioligand, (125)I-labeled 3-(p-hydroxyphenyl)-propionic acid (or
desaminotyrosine) (Hpp)-Aca-SDKP, a biologically active analog of Ac-SDKP. (125)I
labeled Hpp-Aca-SDKP bound to rat CFs and fractionated membranes with similar
affinities and specificity in a concentration- and time-dependent fashion.
Scatchard plot analyses revealed a single class of high-affinity Hpp-Aca-SDKP
binding sites (maximal binding: 1,704 +/- 198 fmol/mg protein; dissociation
constant: 3.3 +/- 0.6 nM). (125)I-labeled Hpp-Aca-SDKP binding in CFs was
displaced by unlabeled native peptide Ac-SDKP (inhibition constant: 0.69 +/- 0.15
nM) and the analog Hpp-Aca-SDKP (inhibition constant: 10.4 +/- 0.2 nM) but not
the unrelated peptide ANG II or ET-1 (10 microM). In vitro, both Ac-SDKP and Hpp
Aca-SDKP inhibited ET-1-stimulated collagen synthesis in CFs in a dose-dependent
fashion, reaching a maximal effect at 1 nM (control: 7.5 +/- 0.4, ET-1: 19.9 +/-
1.2, ET-1+SDKP: 7.7 +/- 0.4, ET-1+Hpp-Aca-SDKP: 9.7 +/- 0.1 microg/mg protein; P
< 0.001). Ac-SDKP also significantly attenuated ET-1-induced increases in
intracellular calcium and MAPK ERK1/2 phosphorylation in CFs. In the rat heart,
in vitro autoradiography revealed specific (125)I-labeled Hpp-Aca-SDKP binding
throughout the myocardium, primarily interstitially. We believe that these
results demonstrate for the first time that Hpp-Aca-SDKP is a functional ligand
specific for Ac-SDKP receptor binding sites and that both Ac-SDKP and Hpp-Aca
SDKP exert antifibrotic effects by binding to Ac-SDKP receptors in rat CFs.
PMID- 17028163
TI - TNF-alpha potentiates protein-tyrosine nitration through activation of NADPH
oxidase and eNOS localized in membrane rafts and caveolae of bovine aortic
endothelial cells.
AB - A major source of reactive oxygen species (ROS) in endothelial cells is the NADPH
oxidase enzyme complex. The selective distributions of any enzyme within cells
have important implications in regulating enzyme effectiveness through
facilitation of access to local substrates and/or product targets. Because
membrane rafts provide a spatially preferable environment for a variety of enzyme
systems, we sought to determine whether NADPH oxidase is present and functional
in this plasma membrane compartment in endothelial cells. We found that, in
resting endothelial cells, NADPH oxidase subunits were preassembled and the
enzyme functional in membrane rafts, specifically in caveolae. Stimulation with
TNF-alpha induced additional recruitment of the p47(phox) regulatory subunit to
raft-localized NADPH oxidase and enhanced ROS production within raft domains. TNF
alpha also induced nitric oxide production through activation of endothelial
nitric oxide synthase (eNOS) present in the same membrane compartment. The dual
activation of superoxide and nitric oxide-generating systems provided a spatially
favorable environment for nitration of tyrosine-containing proteins localized to
rafts. Perturbation of membrane raft structural integrity with cholesterol
sequestering compounds caused the delocalization of NADPH oxidase subunits and
eNOS from the rafts and inhibited TNF-alpha-induced ROS production and protein
tyrosine nitration. Together, these data provide evidence that membrane rafts and
caveolae play a role in the spatial regulation of NADPH oxidase and subsequent
ROS/reactive nitrogen species in endothelial cells.
PMID- 17028164
TI - ANG II type 1A receptor signaling causes unfavorable scar dynamics in the
postinfarct heart.
AB - Blockade of ANG II type 1A receptor (AT(1A)) is known to attenuate postinfarction
[postmyocardial infarction (post-MI)] heart failure, accompanying reduction in
fibrosis of the noninfarcted area. In the present study, we investigated the
influence of AT(1A) blockade on the infarcted tissue itself. Consistent with
earlier reports, AT(1A) knockout (AT(1A)KO) mice showed significantly attenuated
left ventricular (LV) remodeling (dilatation) and dysfunction compared with wild
type (WT) mice. Morphometry revealed that the infarcted wall was thicker and had
a smaller circumferential length in AT(1A)KO than WT hearts. In addition,
significantly greater numbers of cells were present within infarcts in AT(1A)KO
hearts 4 wk post-MI; most notably, there was an abundance of vessels and
myofibroblasts. One week post-MI, the incidence of apoptosis among granulation
tissue cells was fewer (3.3 +/- 0.4 vs. 4.4 +/- 0.5% in WT, P < 0.05), whereas
vessel proliferation was higher in AT(1A)KO hearts, which likely explains the
later abundance of cells within the scar tissue. Insulin-like growth factor
receptor-I was upregulated and its downstream signal protein kinase B (Akt) was
significantly activated in infarcted AT(1A)KO hearts compared with WT hearts.
Inactivation of Akt with wortmannin partially but significantly prevented the
benefits observed in AT(1A)KO. Collectively, in AT(1A)KO hearts, Akt-mediated
granulation tissue cell proliferation and preservation resulting from
antiapoptosis likely contributed to an abundant cell population that altered the
infarct scar structure, thereby reducing wall stress and attenuating LV
dilatation and dysfunction at the chronic stage. In conclusion, altered
structural dynamics of infarct scar and increasing myocardial fibrosis may be
responsible for the deleterious effects of AT(1A) signaling following MI.
PMID- 17028165
TI - Long-term room temperature storage of high-quality embryonic stem cell genomic
DNA extracted with a simple and rapid procedure.
AB - A very simple procedure for the isolation of high-quality, high-molecular-weight
genomic DNA from embryonic stem cells is described. The DNA is very stable once
dried and can be stored for long periods of time without refrigeration. Living
cells are lysed in a sodium dodecyl sulfate and EDTA buffer containing proteinase
K and then air-dried. Samples can be processed in bulk, and an individual can
easily process thousands of samples for extraction and shipment on a daily basis
using only common laboratory materials such as plastic ware and a multichannel
pipetteman.
PMID- 17028166
TI - Biological systems modeling and analysis: a biomolecular technique of the twenty
first century.
AB - It is proposed that computational systems biology should be considered a
biomolecular technique of the twenty-first century, because it complements
experimental biology and bioinformatics in unique ways that will eventually lead
to insights and a depth of understanding not achievable without systems
approaches. This article begins with a summary of traditional and novel modeling
techniques. In the second part, it proposes concept map modeling as a useful link
between experimental biology and biological systems modeling and analysis.
Concept map modeling requires the collaboration between biologist and modeler.
The biologist designs a regulated connectivity diagram of processes comprising a
biological system and also provides semi-quantitative information on stimuli and
measured or expected responses of the system. The modeler converts this
information through methods of forward and inverse modeling into a mathematical
construct that can be used for simulations and to generate and test new
hypotheses. The biologist and the modeler collaboratively interpret the results
and devise improved concept maps. The third part of the article describes
software, BST-Box, supporting the various modeling activities.
PMID- 17028167
TI - In vitro optimization of antisense oligodeoxynucleotide design: an example using
the connexin gene family.
AB - The completion of the human and mouse genomes has identified at least 20 connexin
isomers in this family of intercellular channel proteins. However, there are no
specific gap junction blockers or channel-blocking mimetic peptides available for
the study of specific connexins. We designed antisense oligodeoxynucleotides that
functionally reduce targeted connexin protein expression and can be used to
reveal the biological function of individual connexins in vivo. Connexin mRNA was
firstly exposed in vitro to deoxyribozymes complementing the sense coding
sequence. Those that cleaved the target connexin mRNA in defined regions were
used as the basis to design oligodeoxynucleotides to the accessible sites, thus
taking into account tertiary mRNA configurations rather than relying on computed
predictions. Antisense oligodeoxynucleotides designed to bind to accessible mRNA
sites selectively reduced connexin26 and -43 mRNA expression in a corneal
epithelium ex vivo model. Connexin43 protein levels were reduced correlating with
the knockdown in mRNA and the protein's rapid turnover; protein levels of
connexin26 did not alter, supporting lower turnover rates reported for that
protein. We show, for the first time, an inexpensive and empirical approach to
the preparation of specific and functional antisense oligodeoxynucleotides
against known gene targets in the post-genomic era.
PMID- 17028168
TI - Optimization of the Tet-On system for inducible expression of RAGE.
AB - We have optimized a two-plasmid Tet-On system, the regulatory plasmid and the
response plasmid, to produce tightly controlled inducible expression of the gene
RAGE in cell-culture models. Two sets of plasmids were constructed: set 1
(universal; for broad range of cell types) and set 2 (neuron specific). For the
response plasmid, the gene RAGE was cloned in pIRES2-EGFP plasmid (Clontech) and
the CMV promoter replaced with TREtight (modified seven copies of Tet-operon
fused with CMVm promoter). For the regulatory plasmid, rtTA (reverse tetracycline
transactivator) was placed under either the CMV promoter or the cell-specific
promoter neuronal specific enolase. Both plasmids have the mammalian selection
marker neomycine; the EGFP reporter gene is only in the response plasmid and IRES
is between the gene and EGFP. Following induction with doxycycline, cells
expressing RAGE showed neomycine resistance and green fluorescence (EGFP). Our
system has been tested in two different cell lines and showed negligible basal
leakiness, high induction of the gene RAGE (142-fold), dose-dependent response to
doxycycline, and strict cell-type specificity. This system is highly suitable for
cell-specific expression of any gene of interest in primary cultures and mixed
cell populations.
PMID- 17028169
TI - Critical role for the beta regulatory subunits of Cav channels in T lymphocyte
function.
AB - Calcium ion is a universal signaling intermediate, which is known to control
various biological processes. In excitable cells, voltage-gated calcium channels
(Cav) are the major route of calcium entry and regulate multiple functions such
as contraction, neurotransmitter release, and gene transcription. Here we show
that T lymphocytes, which are nonexcitable cells, express both regulatory beta
and pore-forming Cav1 alpha1 subunits of Cav channels, and we provide genetic
evidence for a critical role of the Cav beta3 and Cav beta4 regulatory subunits
in T lymphocyte function. Cav beta-deficient T lymphocytes fail to acquire normal
functions, and they display impairment in the T cell receptor-mediated calcium
response, nuclear factor of activated T cells activation, and cytokine
production. In addition, unlike in excitable cells, our data suggest a minimal
physiological role for depolarization in Cav channel opening in T cells. T cell
receptor stimulation induces only a small depolarization of T cells, and
artificial depolarization of T cells using KCl does not lead to calcium entry.
These observations suggest that the Cav channels expressed by T cells have
adopted novel regulation/gating mechanisms.
PMID- 17028170
TI - Suppression of hypoxia-induced HIF-1alpha and of angiogenesis in endothelial
cells by myo-inositol trispyrophosphate-treated erythrocytes.
AB - Allosteric regulation of oxygen delivery by RBCs may have significant effects on
tumor growth. Indeed, angiogenesis, the formation of new blood vessels, is
induced in growing tumors by low oxygen partial pressure. Hypoxia-inducible genes
are switched on, among which are the VEGF gene and its receptors. Most important,
under hypoxia, hypoxia-inducible factor 1alpha has a significantly prolonged half
life and up-regulates a number of hypoxia genes. Human microvascular endothelial
cells (MECs), when subjected in vitro to hypoxia, align to form vessel-like
structures as in the angiogenic process. We report here that, when cultured in
hypoxic conditions in the presence of human RBCs loaded with a new membrane
permeant allosteric effector of Hb, myo-inositol trispyrophosphate (ITPP),
endothelial cells (ECs) do not align, i.e., do not form "vessel"-like structures,
because the "loaded" RBCs are capable of releasing under hypoxia more oxygen than
their "normal" counterparts. Levels of VEGF and of hypoxia-inducible factor
1alpha, elevated in the human MECs under hypoxia, were dramatically reduced or
even suppressed in the presence of the ITPP-loaded RBCs. Treatment of these ECs
directly with free ITPP at different concentrations had no effect on their
ability to undertake angiogenesis. Incubation with ITPP enhances the capacity of
Hb to release bound oxygen, leading to higher oxygen tension in the hypoxic
environment, thus inhibiting hypoxia-induced angiogenesis. These observations are
suggestive of a potential in vivo role of ITPP-loaded, "low-O2-affinity" RBCs in
cancer therapy.
PMID- 17028171
TI - miR-7b, a microRNA up-regulated in the hypothalamus after chronic hyperosmolar
stimulation, inhibits Fos translation.
AB - The transcription factor activator protein 1 (AP-1) is formed through the
dimerization of immediate-early genes Fos and Jun family members. Activator
protein 1 is known as a pivotal regulator of major biological events such as cell
proliferation, differentiation, organogenesis, memory formation, and apoptosis.
During a search for microRNAs (miRNAs; small, endogenous, noncoding RNAs that
repress gene expression of target mRNAs in animals posttranscriptionally) that
are differentially expressed in the mouse paraventricular and supraoptic nuclei
after 10 days of drinking 2% saline, one candidate microRNA that is relatively
highly expressed, mmu-miR-7b (miR-7b), was studied further because sequence
analysis suggested a likely interaction with the 3' untranslated region of Fos
mRNA. We show that miR-7b expression inhibits Fos translation in vitro and that
it and its host gene are prominently expressed in the PVN and other brain areas,
including the suprachiasmatic nucleus. No effect on Fos mRNA levels was observed.
Normally, Fos is expressed at low to undetectable levels in cells, but it shows
rapid induction and decay after acute stimuli. Various pathways have been
identified through which Fos family proteins are degraded; our results indicate a
significant additional mechanism by which Fos protein and activity may be
regulated.
PMID- 17028172
TI - Switching off calcium-dependent inactivation in L-type calcium channels by an
autoinhibitory domain.
AB - The retinal L-type Ca2+ channel Cav1.4 is distinguished from all other members of
the high voltage-activated (HVA) Ca2+ channel family by lacking Ca2+-calmodulin
dependent inactivation. In synaptic terminals of photoreceptors and bipolar
cells, this feature is essential to translate graded membrane depolarizations
into sustained Ca2+ influx and tonic glutamate release. The sequences conferring
Ca2+-dependent inactivation (CDI) are conserved throughout the HVA calcium
channel family, raising the question of how Cav1.4 manages to switch off CDI.
Here, we identify an autoinhibitory domain in the distal C terminus of Cav1.4
that serves to abolish CDI. We show that this domain (ICDI, inhibitor of CDI)
uncouples the molecular machinery conferring CDI from the inactivation gate by
binding to the EF hand motif in the proximal C terminus. Deletion of ICDI
completely restores Ca2+-calmodulin-mediated CDI in Cav1.4. CDI can be switched
off again in the truncated Cav1.4 channel by coexpression of ICDI, indicating
that ICDI works as an autonomous unit. Furthermore, we show that in the Cav1.2 l
type Ca2+-channel replacement of the distal C terminus by the corresponding
sequence of Cav1.4 is sufficient to block CDI. This finding suggests that
autoinhibition of CDI can be introduced principally into other Ca2+ channel
types. Our data provide a previously undescribed perspective on the regulation of
HVA calcium channels by Ca2+.
PMID- 17028173
TI - A deletion defining a common Asian lineage of Mycobacterium tuberculosis
associates with immune subversion.
AB - Six major lineages of Mycobacterium tuberculosis appear preferentially
transmitted amongst distinct ethnic groups. We identified a deletion affecting
Rv1519 in CH, a strain isolated from a large outbreak in Leicester U.K., that
coincidentally defines the East African-Indian lineage matching a major ethnic
group in this city. In broth media, CH grew less rapidly and was less acidic and
H2O2-tolerant than reference sequenced strains (CDC1551 and H37Rv). Nevertheless,
CH was not impaired in its ability to grow in human monocyte-derived macrophages.
When compared with CDC1551 and H37Rv, CH induced less protective IL-12p40 and
more antiinflammatory IL-10 and IL-6 gene transcription and secretion from
monocyte-derived macrophages. It thus appears that CH compensates microbiological
attenuation by skewing the innate response toward phagocyte deactivation.
Complementation of Rv1519, but none of nine additional genes absent from CH
compared with the type strain, H37Rv, reversed the capacity of CH to elicit
antiinflammatory IL-10 production by macrophages. The Rv1519 polymorphism in M.
tuberculosis confers an immune subverting phenotype that contributes to the
persistence and outbreak potential of this lineage.
PMID- 17028174
TI - Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and
AMPK, and is involved in AMPK and mTOR signaling.
AB - Birt-Hogg-Dube syndrome, a hamartoma disorder characterized by benign tumors of
the hair follicle, lung cysts, and renal neoplasia, is caused by germ-line
mutations in the BHD(FLCN) gene, which encodes a tumor-suppressor protein,
folliculin (FLCN), with unknown function. The tumor-suppressor proteins encoded
by genes responsible for several other hamartoma syndromes, LKB1, TSC1/2, and
PTEN, have been shown to be involved in the mammalian target of rapamycin (mTOR)
signaling pathway. Here, we report the identification of the FLCN-interacting
protein, FNIP1, and demonstrate its interaction with 5' AMP-activated protein
kinase (AMPK), a key molecule for energy sensing that negatively regulates mTOR
activity. FNIP1 was phosphorylated by AMPK, and its phosphorylation was reduced
by AMPK inhibitors, which resulted in reduced FNIP1 expression. AMPK inhibitors
also reduced FLCN phosphorylation. Moreover, FLCN phosphorylation was diminished
by rapamycin and amino acid starvation and facilitated by FNIP1 overexpression,
suggesting that FLCN may be regulated by mTOR and AMPK signaling. Our data
suggest that FLCN, mutated in Birt-Hogg-Dube syndrome, and its interacting
partner FNIP1 may be involved in energy and/or nutrient sensing through the AMPK
and mTOR signaling pathways.
PMID- 17028175
TI - Inhomogeneous dynamics in confined water nanodroplets.
AB - The effect of confinement on the dynamical properties of liquid water was studied
by mid-infrared ultrafast pump-probe spectroscopy on HDO:D2O in reverse micelles.
By preparing water-containing reverse micelles of different well defined sizes,
we varied the degree of geometric confinement in water nanodroplets with radii
ranging from 0.2 to 4.5 nm. We find that water molecules located near the
interface confining the droplet exhibit slower vibrational energy relaxation and
have a different spectral absorption than those located in the droplet core. As a
result, we can measure the orientational dynamics of these different types of
water with high selectivity. We observe that the water molecules in the core show
similar orientational dynamics as bulk water and that the water layer solvating
the interface is highly immobile.
PMID- 17028176
TI - Chlamydial TARP is a bacterial nucleator of actin.
AB - Chlamydia trachomatis entry into host cells results from a parasite-directed
remodeling of the actin cytoskeleton. A type III secreted effector, TARP
(translocated actin recruiting phosphoprotein), has been implicated in the
recruitment of actin to the site of internalization. To elucidate the role of
TARP in actin recruitment, we identified host cell proteins that associated with
recombinant GST-TARP fusions. TARP directly associated with actin, and this
interaction promoted actin nucleation as determined by in vitro polymerization
assays. Domain analysis of TARP identified an actin-binding domain that bears
structural and primary amino acid sequence similarity to WH2 domain family
proteins. In addition, a proline-rich domain was found to promote TARP
oligomerization and was required for TARP-dependent nucleation of new actin
filaments. Our findings reveal a mechanism by which chlamydiae induce localized
cytoskeletal changes by the translocated effector TARP during entry into host
cells.
PMID- 17028177
TI - Fronto-cerebellar systems are associated with infant motor and adult executive
functions in healthy adults but not in schizophrenia.
AB - Delineating longitudinal relationships between early developmental markers, adult
cognitive function, and adult brain structure could clarify the pathogenesis of
neurodevelopmental disorders such as schizophrenia. We aimed to identify brain
structural correlates of infant motor development (IMD) and adult executive
function in nonpsychotic adults and to test for abnormal associations between
these measures in people with schizophrenia. Representative samples of
nonpsychotic adults (n = 93) and people with schizophrenia (n = 49) were drawn
from the Northern Finland 1966 general population birth cohort. IMD was
prospectively assessed at age 1 year; executive function testing and MRI were
completed at age 33-35 years. We found that earlier motor development in infancy
was correlated with superior executive function in nonpsychotic subjects. Earlier
motor development was also normally associated with increased gray matter density
in adult premotor cortex, striatum, and cerebellum and increased white matter
density in frontal and parietal lobes. Adult executive function was normally
associated with increased gray matter density in a fronto-cerebellar system that
partially overlapped, but was not identical to, the gray matter regions normally
associated with IMD. People with schizophrenia had relatively delayed IMD and
impaired adult executive function in adulthood. Furthermore, they demonstrated no
normative associations between fronto-cerebellar structure, IMD, or executive
function. We conclude that frontal cortico-cerebellar systems correlated with
adult executive function are anatomically related to systems associated with
normal infant motor development. Disruption of this anatomical system may
underlie both the early developmental and adult cognitive abnormalities in
schizophrenia.
PMID- 17028178
TI - The deubiquitinating enzyme Ubp2 modulates Rsp5-dependent Lys63-linked
polyubiquitin conjugates in Saccharomyces cerevisiae.
AB - The functions of Lys(63)-linked polyubiquitin chains are poorly understood, as
are the enzymes that specifically generate Lys(63)-linked conjugates. Rsp5 is a
HECT (homologous to E6AP C terminus) ubiquitin ligase involved in numerous
processes, and an associated deubiquitinating enzyme, Ubp2, modulates its
activity. A dramatic increase in Lys(63)-linked conjugates was observed in
ubp2Delta cells. The formation of these was Rsp5-dependent, and ubp2Delta
phenotypes could be suppressed by prevention of formation of Lys(63) conjugates.
Cell wall integrity was impaired in rsp5-1 cells and in cells defective in
Lys(63)-polyubiquitination, as assayed by calcofluor white sensitivity, and
ubp2Delta and rup1Delta mutants suppressed the calcofluor white sensitivity of
rsp5-1. A large fraction of the Lys(63) conjugates in ubp2Delta cells bound to
Rsp5, and a proteomics approach was used to identify Rsp5 substrates subject to
Ubp2 regulation. Two closely related proteins, Csr2 and Ecm21, were among the
identified proteins. Both were efficiently Lys(63)-polyubiquitinated by Rsp5 and
deubiquitinated by Ubp2. Together, these results indicate that Ubp2 modulates
Lys(63)-polyubiquitination of Rsp5 substrates in vivo, including ubiquitination
of two newly identified Rsp5 substrates.
PMID- 17028179
TI - A multienzyme network functions in intestinal protein digestion by a
platyhelminth parasite.
AB - Proteases frequently function not only as individual enzymes but also in cascades
or networks. A notable evolutionary switch occurred in one such protease network
that is involved in protein digestion in the intestine. In vertebrates, this is
largely the work of trypsin family serine proteases, whereas in invertebrates,
cysteine proteases of the papain family and aspartic proteases assume the role.
Utilizing a combination of protease class-specific inhibitors and RNA
interference, we deconvoluted such a network of major endopeptidases functioning
in invertebrate intestinal protein digestion, using the parasitic helminth,
Schistosoma mansoni as an experimental model. We show that initial degradation of
host blood proteins is ordered, occasionally redundant, and substrate-specific.
Although inhibition of parasite cathepsin D had a greater effect on primary
cleavage of hemoglobin, inhibition of cathepsin B predominated in albumin
degradation. Nevertheless, in both cases, inhibitor combinations were
synergistic. An asparaginyl endopeptidase (legumain) also synergized with
cathepsin B and L in protein digestion, either by zymogen activation or
facilitating substrate cleavage. This protease network operates optimally in
acidic pH compartments either in the gut lumen or in vacuoles of the intestinal
lining cells. Defining the role of each of these major enzymes now provides a
clearer understanding of the function of a complex protease network that is
conserved throughout invertebrate evolution. It also provides insights into which
of these proteases are logical targets for development of chemotherapy for
schistosomiasis, a major global health problem.
PMID- 17028180
TI - Transcriptional regulation by Foxp3 is associated with direct promoter occupancy
and modulation of histone acetylation.
AB - Regulatory T cells (T(reg)) express Foxp3, a forkhead family member that is
necessary and sufficient for T(reg) lineage choice and function. Ectopic
expression of Foxp3 in non-T(reg) leads to repression of the interleukin 2 (IL-2)
and interferon gamma (IFNgamma) genes, gain of suppressor function, and induction
of genes such as CD25, GITR, and CTLA-4, but the mode by which Foxp3 enforces
this program is unclear. Using chromatin immunoprecipitation, we have
demonstrated that Foxp3 binds to the endogenous IL-2 and IFNgamma loci in T
cells, but only after T cell receptor stimulation. This activation-induced Foxp3
binding was abrogated by cyclosporin A, suggesting a role for the phosphatase
calcineurin in Foxp3 function. We have also shown that binding of Foxp3 to the IL
2 and IFNgamma genes induces active deacetylation of histone H3, a process that
inhibits chromatin remodeling and opposes gene transcription. Conversely, binding
of Foxp3 to the GITR, CD25, and CTLA-4 genes results in increased histone
acetylation. These data indicate that Foxp3 may regulate transcription through
direct chromatin remodeling and show that Foxp3 function is influenced by signals
from the TCR.
PMID- 17028181
TI - Expression of expanded polyglutamine proteins suppresses the activation of
transcription factor NFkappaB.
AB - A major pathological hallmark of the polyglutamine diseases is the formation of
neuronal intranuclear inclusions of the disease proteins that are ubiquitinated
and often associated with various transcription factors, chaperones, and
proteasome components. However, how the expanded polyglutamine proteins or their
aggregates elicit complex pathogenic responses in the neuronal cells is not fully
understood. Here, we have demonstrated that the expression of expanded
polyglutamine proteins down-regulated the NFkappaB-dependent transcriptional
activity. The expression of expanded polyglutamine proteins increased the
stability and the levels of IkappaB-alpha and its phosphorylated derivatives. We
have also found that various NFkappaB subunits and IkappaB-alpha aberrantly
interacted with the expanded polyglutamine proteins and associated with their
aggregates. Finally, we have shown that several NFkappaB-dependent genes are down
regulated in the expanded polyglutamine protein-expressing cells and down
regulation of NFkappaB activity enhances expanded polyglutamine protein-induced
cell death. Because the NFkappaB pathway plays a very important role in cell
survival, altered regulation of this pathway in expanded polyglutamine protein
expressing cells might be linked with the disease pathogenesis.
PMID- 17028182
TI - Structural insights into the design of nonpeptidic isothiazolidinone-containing
inhibitors of protein-tyrosine phosphatase 1B.
AB - Structural analyses of the protein-tyrosine phosphatase 1B (PTP1B) active site
and inhibitor complexes have aided in optimization of a peptide inhibitor
containing the novel (S)-isothiazolidinone (IZD) phosphonate mimetic. Potency and
permeability were simultaneously improved by replacing the polar peptidic
backbone of the inhibitor with nonpeptidic moieties. The C-terminal primary amide
was replaced with a benzimidazole ring, which hydrogen bonds to the carboxylate
of Asp(48), and the N terminus of the peptide was replaced with an aryl
sulfonamide, which hydrogen bonds to Asp(48) and the backbone NH of Arg(47) via a
water molecule. Although both substituents retain the favorable hydrogen bonding
network of the peptide scaffold, their aryl rings interact weakly with the
protein. The aryl ring of benzimidazole is partially solvent exposed and only
participates in van der Waals interactions with Phe(182) of the flap. The aryl
ring of aryl sulfonamide adopts an unexpected conformation and only participates
in intramolecular pi-stacking interactions with the benzimidazole ring. These
results explain the flat SAR for substitutions on both rings and the reason why
unsubstituted moieties were selected as candidates. Finally, substituents ortho
to the IZD heterocycle on the aryl ring of the IZD-phenyl moiety bind in a small
narrow site adjacent to the primary phosphate binding pocket. The crystal
structure of an o-chloro derivative reveals that chlorine interacts extensively
with residues in the small site. The structural insights that have led to the
discovery of potent benzimidazole aryl sulfonamide o-substituted derivatives are
discussed in detail.
PMID- 17028183
TI - Crystal structure of the Mycobacterium tuberculosis P450 CYP121-fluconazole
complex reveals new azole drug-P450 binding mode.
AB - Azole and triazole drugs are cytochrome P450 inhibitors widely used as fungal
antibiotics and possessing potent antimycobacterial activity. We present here the
crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP121 in complex
with the triazole drug fluconazole, revealing a new azole heme ligation mode. In
contrast to other structurally characterized cytochrome P450 azole complexes,
where the azole nitrogen directly coordinates the heme iron, in CYP121
fluconazole does not displace the aqua sixth heme ligand but occupies a position
that allows formation of a direct hydrogen bond to the aqua sixth heme ligand.
Direct ligation of fluconazole to the heme iron is observed in a minority of
CYP121 molecules, albeit with severe deviations from ideal geometry due to close
contacts with active site residues. Analysis of both ligand-on and -off
structures reveals the relative position of active site residues derived from the
I-helix is a key determinant in the relative ratio of on and off states.
Regardless, both ligand-bound states lead to P450 inactivation by active site
occlusion. This previously unrecognized means of P450 inactivation is consistent
with spectroscopic analyses in both solution and in the crystalline form and
raises important questions relating to interaction of azoles with both pathogen
and human P450s.
PMID- 17028184
TI - L4-33K, an adenovirus-encoded alternative RNA splicing factor.
AB - Splicing of the adenovirus IIIa mRNA is subjected to a strict temporal regulation
during virus infection such that efficient IIIa 3' splice site usage is confined
to the late phase of the infectious cycle. Here we show that the adenovirus L4
33K protein functions as a virus-encoded RNA splicing factor that preferentially
activates splicing of transcripts with a weak 3' splice site sequence context, a
sequence configuration that is shared by many of the late adenovirus 3' splice
sites. Furthermore, we show that L4-33K activates IIIa splicing through the IIIa
virus infection-dependent splicing enhancer element (3VDE). This element was
previously shown to be the minimal element, both necessary and sufficient, for
activation of IIIa splicing in the context of an adenovirus-infected cell. L4-33K
stimulates an early step in spliceosome assembly and appears to be the only viral
protein necessary to convert a nuclear extract prepared from uninfected HeLa
cells to an extract with splicing properties very similar to a nuclear extract
prepared from adenovirus late-infected cells. Collectively, our results suggest
that L4-33K is the key viral protein required to activate the early to late
switch in adenovirus major late L1 alternative splicing.
PMID- 17028185
TI - Loss of SOCS3 gene expression converts STAT3 function from anti-apoptotic to pro
apoptotic.
AB - The transcription factor STAT3 is activated by interleukin-6-related cytokines
and has been implicated as an oncogene; it promotes cell proliferation and is
anti-apoptotic. However, in some cases, STAT3 has been shown to be pro-apoptotic,
especially in mammary epithelial cells. In this report, we generated SOCS3
deficient murine embryonic fibroblasts (MEFs), in which STAT3 activation is
extremely enhanced and prolonged. We found that LIF induces caspase-3 activation
and apoptosis of SOCS3(-/-) MEFs. Exogenous expression of the dominant negative
form of STAT3 but not STAT1 suppressed LIF-induced apoptosis of SOCS3(-/-) MEFs,
indicating that STAT3 plays a critical role in apoptosis induction. As shown in
mammary gland epithelial cells, expression of the phosphatidylinositol 3-kinase
regulatory subunits p50alpha and p55alpha was induced in response to LIF in
SOCS3(-/-) MEFs but not in wild-type MEFs, and Akt/protein kinase B activity was
substantially reduced in SOCS3(-/-) MEFs. Furthermore, we found that some of the
STAT3 target genes related to apoptosis and proliferation, such as Bcl-2 and
cyclin D1, were repressed upon LIF treatment in SOCS3(-/-) cells. Not only the up
regulation of p50alpha and p55alpha but also the repression of cyclin D1 and Bcl
2 in SOCS3(-/-) MEFs was inhibited by dominant negative STAT3. These data suggest
that prolonged activation of STAT3 could induce apoptosis/growth arrest rather
than anti-apoptosis and proliferation in certain cases, and SOCS3 is a critical
regulator of this balance.
PMID- 17028186
TI - Molecular and functional characterization of a soluble form of oncostatin
M/interleukin-31 shared receptor.
AB - Activation of the signaling transduction pathways mediated by oncostatin M (OSM)
requires the binding of the cytokine to either type I OSM receptor (leukemia
inhibitory factor receptor/gp130) or to type II OSM receptor (OSMR/gp130). In the
present work we have developed an enzyme-linked immunosorbent assay detecting a
soluble form of OSMR (sOSMR) secreted by glioblastoma, hepatoma, and melanoma
tumor cell lines. sOSMR was also present in sera of healthy individuals, with
increased levels in multiple myeloma. Molecular cloning of a corresponding cDNA
was carried out, and it encoded for a 70-kDa protein consisting of a half
cytokine binding domain containing the canonical WSXWS motif, an immunoglobulin
like domain, and the first half of a second cytokine binding domain with
cysteines in fixed positions. Analysis of the soluble receptor distribution
revealed a preferential expression in lung, liver, pancreas, and placenta. sOSMR
was able to bind OSM and interleukin-31 when associated to soluble gp130 or
soluble interleukin-31R, respectively, and to neutralize both cytokine
properties. We have also shown that OSM could positively regulate the synthesis
of its own soluble receptor in tumor cells.
PMID- 17028187
TI - Structural characterization of a blue chromoprotein and its yellow mutant from
the sea anemone Cnidopus japonicus.
AB - Green fluorescent protein (GFP) and its relatives (GFP protein family) have been
isolated from marine organisms such as jellyfish and corals that belong to the
phylum Cnidaria (stinging aquatic invertebrates). They are intrinsically
fluorescent proteins. In search of new members of the family of green fluorescent
protein family, we identified a non-fluorescent chromoprotein from the Cnidopus
japonicus species of sea anemone that possesses 45% sequence identity to dsRed (a
red fluorescent protein). This newly identified blue color protein has an
absorbance maximum of 610 nm and is hereafter referred to as cjBlue.
Determination of the cjBlue 1.8 A crystal structure revealed a chromophore
comprised of Gln(63)-Tyr(64)-Gly(65). The ring stacking between Tyr(64) and
His(197) stabilized the cjBlue trans chromophore conformation along the Calpha2
Cbeta2 bond of 5-[(4-hydroxyphenyl)methylene]-imidazolinone, which closely
resembled that of the "Kindling Fluorescent Protein" and Rtms5. Replacement of
Tyr(64) with Leu in wild-type cjBlue produced a visible color change from blue to
yellow with a new absorbance maximum of 417 nm. Interestingly, the crystal
structure of the yellow mutant Y64L revealed two His(197) imidazole ring
orientations, suggesting a flip-flop interconversion between the two
conformations in solution. We conclude that the dynamics and structure of the
chromophore are both essential for the optical appearance of these color
proteins.
PMID- 17028188
TI - Oncostatin M inhibits adipogenesis through the RAS/ERK and STAT5 signaling
pathways.
AB - Adipocytes play a key role in energy homeostasis and several cytokines have been
shown to regulate adipogenesis. While the interleukin (IL)-6 family of cytokines
was previously reported to be involved in adipogenesis, roles of this family in
adipogenesis and their mechanisms of action are not fully understood. Here we
show that among the IL-6 family, oncostatin M (OSM) most strongly inhibits
adipogenesis of 3T3-L1 cells and mouse embryonic fibroblasts (MEFs). We also
demonstrate that OSM inhibits adipogenesis through the Ras/extracellular signal
regulated kinase (ERK) and signal transducer and activator of transcription
(STAT) 5 signaling pathways. In addition, OSM inhibits the early phase of the
differentiation without affecting cell proliferation throughout adipogenesis
including mitotic clonal expansion. CCAAT/enhancer-binding protein (C/EBP) alpha,
C/EBPbeta, and peroxisome proliferator-activated receptor (PPAR) gamma are known
to be required for adipogenesis. Expression of C/EBPalpha and PPARgamma was
almost completely abrogated by OSM. In contrast, neither the mRNA nor protein
level of C/EBPbeta was affected by OSM. Forced expression of C/EBPbeta induced
differentiation in the presence of troglitazone, and OSM inhibited this C/EBPbeta
induced differentiation. Taken together, our results indicate that OSM inhibits
the onset of terminal differentiation of adipocytes through the Ras/ERK and STAT5
signaling pathways by possibly regulating C/EBPbeta activity.
PMID- 17028189
TI - Trim5alpha accelerates degradation of cytosolic capsid associated with productive
HIV-1 entry.
AB - The TRIM5alpha (tripartite motif 5alpha protein) has been linked to the cross
species restriction in human immunodeficiency virus type 1 (HIV-1) infection of
non-human cells, but the mechanism by which this occurs remains to be fully
elucidated. Here we demonstrate that the capsid (CA) protein of HIV-1 is more
rapidly degraded in cells expressing monkey TRIM5alpha than in cells expressing
human TRIM5alpha. Other proteins encoded by Gag and Pol are not subject to
TRIM5alpha-mediated accelerated degradation. The accelerated CA degradation by
TRIM5alpha apparently occurs via a nonproteosomal pathway. TRIM5alpha selectively
accelerates degradation of the CA population, which reached the cytosol of
restrictive cells, but not the CA population, which ended into the vesicular
compartment. Given that cytosolic CA represents "productively" entered cores,
whereas vesicular CA represents "nonproductively" entered cores, our findings
suggest that TRIM5alpha interrupts the infectious pathway of HIV-1 by acting on
the incoming cytosolic CA. The mode of viral entry does not influence the
accelerated degradation of cytosolic CA by TRIM5alpha. Thus, this study reveals a
correlation between TRIM5alpha-mediated HIV-1 restriction and a selective
degradation of cytosolic CA normally associated with productive viral entry.
PMID- 17028190
TI - Mechanistic and structural studies of apoform, binary, and ternary complexes of
the Arabidopsis alkenal double bond reductase At5g16970.
AB - In this study, we determined the crystal structures of the apoform, binary, and
ternary complexes of the Arabidopsis alkenal double bond reductase encoded by
At5g16970. This protein, one of 11 homologues in Arabidopsis thaliana, is most
closely related to the Pinus taeda phenylpropenal double bond reductase, involved
in, for example, heartwood formation. Both enzymes also have essential roles in
plant defense, and can function by catalyzing the reduction of the 7-8-double
bond of phenylpropanal substrates, such as p-coumaryl and coniferyl aldehydes in
vitro. At5g16970 is also capable of reducing toxic substrates with the same
alkenal functionality, such as 4-hydroxy-(2E)-nonenal. The overall fold of
At5g16970 is similar to that of the zinc-independent medium chain
dehydrogenase/reductase superfamily, the members of which have two domains and
are dimeric in nature, i.e. in contrast to their original classification as being
zinc-containing oxidoreductases. As provisionally anticipated from the kinetic
data, the shape of the binding pocket can readily accommodate p-coumaryl
aldehyde, coniferyl aldehyde, 4-hydroxy-(2E)-nonenal, and 2-alkenals. However,
the enzyme kinetic data among these potential substrates differ, favoring p
coumaryl aldehyde. Tyr-260 is provisionally proposed to function as a general
acid/base for hydride transfer. A catalytic mechanism for this reduction, and its
applicability to related important detoxification mammalian proteins, is also
proposed.
PMID- 17028191
TI - Intracranial microenvironment reveals independent opposing functions of host
alphaVbeta3 expression on glioma growth and angiogenesis.
AB - alphaVbeta3 integrins are overexpressed in the host-derived vasculature of
glioblastoma multiform (GBM) and are believed to contribute to angiogenesis and
tumor growth. To directly address the role of host alphaVbeta3 expression in GBM
growth and behavior, we intracranially implanted integrin beta3-expressing GBM
cells into beta3 wild type (WT) or beta3 knock out (KO) mice and monitored
angiogenesis and growth. GBM in beta3 WT animals had a vessel density greater
than that in beta3 KO animals, consistent with a pro-angiogenic, pro-tumorigenic
view of host integrin function. GBM in beta3 WT animals, however, were no larger
than those in beta3 KO animals, because GBM in beta3WT animals were infiltrated
with a higher number of tumor necrosis factor alpha-secreting, apoptosis-inducing
macrophages than the tumors in the corresponding beta3 KO animals. The tumor
suppressive effects of host beta3 expression could be reversed by macrophage
depletion or by transplantation of bone marrow from beta3 KO animals into beta3
WT animals, both of which significantly increased tumor growth independently of
tumor vessel density. Taken together, these results show that host alphaVbeta3
integrin expression has opposing actions in the intracranial setting, enhancing
tumor vascularization and growth while independently enhancing macrophage
mediated tumor elimination. Appropriate management of these functions could lead
to enhanced efficacy of anti-integrin based therapies for glioma.
PMID- 17028192
TI - An allosteric activator of glucokinase impairs the interaction of glucokinase and
glucokinase regulatory protein and regulates glucose metabolism.
AB - Glucokinase (GK) plays a key role in the control of blood glucose homeostasis. We
identified a small molecule GK activator, compound A, that increased the glucose
affinity and maximal velocity (V(max)) of GK. Compound A augmented insulin
secretion from isolated rat islets and enhanced glucose utilization in primary
cultured rat hepatocytes. In rat oral glucose tolerance tests, orally
administrated compound A lowered plasma glucose elevation with a concomitant
increase in plasma insulin and hepatic glycogen. In liver, GK activity is acutely
controlled by its association to the glucokinase regulatory protein (GKRP). In
order to decipher the molecular aspects of how GK activator affects the shuttling
of GK between nucleus and cytoplasm, the effect of compound A on GK-GKRP
interaction was further investigated. Compound A increased the level of
cytoplasmic GK in both isolated rat primary hepatocytes and the liver tissues
from rats. Experiments in a cell-free system revealed that compound A interacted
with glucose-bound free GK, thereby impairing the association of GK and GKRP. On
the other hand, compound A did not bind to glucose-unbound GK or GKRP-associated
GK. Furthermore, we found that glucose-dependent GK-GKRP interaction also
required ATP. Given the combined prominent role of GK on insulin secretion and
hepatic glucose metabolism where the GK-GKRP mechanism is involved, activation of
GK has a new therapeutic potential in the treatment of type 2 diabetes.
PMID- 17028193
TI - Overexpression of rat long chain acyl-coa synthetase 1 alters fatty acid
metabolism in rat primary hepatocytes.
AB - Long chain acyl-CoA synthetases (ACSL) activate fatty acids (FA) and provide
substrates for both anabolic and catabolic pathways. We have hypothesized that
each of the five ACSL isoforms partitions FA toward specific downstream pathways.
Acsl1 mRNA is increased in cells under both lipogenic and oxidative conditions.
To elucidate the role of ACSL1 in hepatic lipid metabolism, we overexpressed an
Acsl1 adenovirus construct (Ad-Acsl1) in rat primary hepatocytes. Ad-ACSL1,
located on the endoplasmic reticulum but not on mitochondria or plasma membrane,
increased ACS specific activity 3.7-fold. With 100 or 750 mum [1-(14)C]oleate, Ad
Acsl1 increased oleate incorporation into diacylglycerol and phospholipids,
particularly phosphatidylethanolamine and phosphatidylinositol, and decreased
incorporation into cholesterol esters and secreted triacylglycerol. Ad-Acsl1 did
not alter oleate incorporation into triacylglycerol, beta-oxidation products, or
total amount of FA metabolized. In pulse-chase experiments to examine the effects
of Ad-Acsl1 on lipid turnover, more labeled triacylglycerol and phospholipid, but
less labeled diacylglycerol, remained in Ad-Acsl1 cells, suggesting that ACSL1
increased reacylation of hydrolyzed oleate derived from triacylglycerol and
diacylglycerol. In addition, less hydrolyzed oleate was used for cholesterol
ester synthesis and beta-oxidation. The increase in [1,2,3-(3)H]glycerol
incorporation into diacylglycerol and phospholipid was similar to the increase
with [(14)C]oleate labeling suggesting that ACSL1 increased de novo synthesis.
Labeling Ad-Acsl1 cells with [(14)C]acetate increased triacylglycerol synthesis
but did not channel endogenous FA away from cholesterol ester synthesis. Thus,
consistent with the hypothesis that individual ACSLs partition FA, Ad-Acsl1
increased FA reacylation and channeled FA toward diacylglycerol and phospholipid
synthesis and away from cholesterol ester synthesis.
PMID- 17028194
TI - Involvement of p38alpha mitogen-activated protein kinase in lung metastasis of
tumor cells.
AB - To study the role of p38 mitogen-activated protein kinase (p38) activity during
the process of metastasis, p38alpha(+/-) mice were subjected to an in vivo
metastasis assay. The number of lung colonies of tumor cells intravenously
injected in p38alpha(+/-) mice was markedly decreased compared with that in wild
type (WT) mice. On the other hand, the time-dependent increase in tumor volume
after subcutaneous tumor cells transplantation was comparable between WT and
p38alpha(+/-) mice. Platelets of p38alpha(+/-) mice were poorly bound to tumor
cells in vitro and in vivo compared with those of WT mice. E- and P-selectin
mRNAs were markedly induced in the lung after intravenous injection of tumor
cells. However, the induction of these selectin mRNAs in p38alpha(+/-) mice was
weaker than that in WT mice. Furthermore, the resting expression levels of E
selectin in lung endothelial cells and P-selectin in platelets of p38alpha(+/-)
mice were suppressed compared with those of WT mice. The number of tumor cells
attached on lung endothelial cells of p38alpha(+/-) mice was significantly
reduced compared with that of WT mice. The transmigrating activity of tumor cells
through lung endothelial cells of p38alpha(+/-) mice was similar to that of WT
mice. These results suggest that p38alpha plays an important role in
extravasation of tumor cells, possibly through regulating the formation of tumor
platelet aggregates and their interaction with the endothelium involved in a step
of hematogenous metastasis.
PMID- 17028195
TI - Mitochondrial creatine kinase activity prevents reactive oxygen species
generation: antioxidant role of mitochondrial kinase-dependent ADP re-cycling
activity.
AB - As recently demonstrated by our group (da-Silva, W. S., Gomez-Puyou, A., Gomez
Puyou, M. T., Moreno-Sanchez, R., De Felice, F. G., de Meis, L., Oliveira, M. F.,
and Galina, A. (2004) J. Biol. Chem. 279, 39846-39855) mitochondrial hexokinase
activity (mt-HK) plays a preventive antioxidant role because of steady-state ADP
re-cycling through the inner mitochondrial membrane in rat brain. In the present
work we show that ADP re-cycling accomplished by the mitochondrial creatine
kinase (mt-CK) regulates reactive oxygen species (ROS) generation, particularly
in high glucose concentrations. Activation of mt-CK by creatine (Cr) and ATP or
ADP, induced a state 3-like respiration in isolated brain mitochondria and
prevention of H(2)O(2) production obeyed the steady-state kinetics of the enzyme
to phosphorylate Cr. The extension of the preventive antioxidant role of mt-CK
depended on the phosphocreatine (PCr)/Cr ratio. Rat liver mitochondria, which
lack mt-CK activity, only reduced state 4-induced H(2)O(2) generation when 1
order of magnitude more exogenous CK activity was added to the medium. Simulation
of hyperglycemic conditions, by the inclusion of glucose 6-phosphate in
mitochondria performing 2-deoxyglucose phosphorylation via mt-HK, induced
H(2)O(2) production in a Cr-sensitive manner. Simulation of hyperglycemia in
embryonic rat brain cortical neurons increased both DeltaPsi(m) and ROS
production and both parameters were decreased by the previous inclusion of Cr.
Taken together, the results presented here indicate that mitochondrial kinase
activity performed a key role as a preventive antioxidant against oxidative
stress, reducing mitochondrial ROS generation through an ADP-recycling mechanism.
PMID- 17028196
TI - Adenomatous polyposis coli control of C-terminal binding protein-1 stability
regulates expression of intestinal retinol dehydrogenases.
AB - Mutations in the human adenomatous polyposis coli (APC) gene are thought to
initiate colorectal tumorigenesis. The tumor suppressor function of APC is
attributed primarily to its ability to regulate the WNT pathway by targeting the
destruction of beta-catenin. We report here a novel role for APC in regulating
degradation of the transcriptional co-repressor C-terminal-binding protein-1
(CtBP1) through a proteasome-dependent process. Further, CtBP1 suppresses the
expression of intestinal retinol dehydrogenases, which are required for retinoic
acid production and intestinal differentiation. In support of a role for CtBP1 in
initiation of colorectal cancer, adenomas taken from individuals with familial
adenomatous polyposis contain high levels of CtBP1 protein in comparison with
matched, uninvolved tissue. The relationship between APC and CtBP1 is conserved
between humans and zebrafish and provides a mechanistic model explaining APC
control of intestinal retinoic acid biosynthesis.
PMID- 17028197
TI - Low molecular weight fucoidan increases VEGF165-induced endothelial cell
migration by enhancing VEGF165 binding to VEGFR-2 and NRP1.
AB - Therapeutic induction of angiogenesis is a potential treatment for chronic
ischemia. Heparan sulfate proteoglycans are known to play an important role by
their interactions with proangiogenic growth factors such as vascular endothelial
growth factor (VEGF). Low molecular weight fucoidan (LMWF), a sulfated
polysaccharide from brown seaweeds that mimic some biological activities of
heparin, has been shown recently to promote revascularization in rat critical
hindlimb ischemia. In this report, we first used cultured human endothelial cells
(ECs) to investigate the possible ability of LMWF to enhance the actions of
VEGF(165). Data showed that LMWF greatly enhances EC tube formation in growth
factor reduced matrigel. LMWF is a strong enhancer of VEGF(165)-induced EC
chemotaxis, but not proliferation. In addition, LMWF has no effect on VEGF(121)
induced EC migration, a VEGF isoform that does not bind to heparan sulfate
proteoglycans. Then, with binding studies using (125)I-VEGF(165), we observed
that LMWF enhances the binding of VEGF(165) to recombinant VEGFR-2 and Neuropilin
1 (NRP1), but not to VEGFR-1. Surface plasmon resonance analysis showed that LMWF
binds with high affinity to VEGF(165) (1.2 nm) and its receptors (5-20 nm), but
not to VEGF(121). Pre-injection of LMWF on immobilized receptors shows that
VEGF(165) has the highest affinity for VEGFR-2 and NRP1, as compared with VEGFR
1. Overall, the effects of LMWF were much more pronounced than those of LMW
heparin. These findings suggested an efficient mechanism of action of LMWF by
promoting VEGF(165) binding to VEGFR-2 and NRP1 on ECs that could help in
stimulating therapeutic revascularization.
PMID- 17028198
TI - RalA-exocyst-dependent recycling endosome trafficking is required for the
completion of cytokinesis.
AB - In eukaryotic cells, recycling endosome-mediated trafficking contributes to the
completion of cytokinesis, in a manner under the control of the centrosome. We
report that the exocyst complex and its interacting GTPase RalA play a critical
role in this polarized trafficking process. RalA resides in the recycling
endosome and relocates from the pericentrosomal region to key cytokinetic
structures including the cleavage furrow, and later, the abscission site. This
event is coupled to the dynamic redistribution of the exocyst proteins. These
associate with the centrosome in interphase and concentrate on the central
spindle/midbody during cytokinesis. Disruption of RalA-exocyst function leads to
cytokinesis failure in late stages, particularly abscission, resembling the
cytokinesis defects induced by loss of centrosome function. These data suggest
that RalA and the exocyst may regulate vesicle delivery to the centrosome-related
abscission site during the terminal stage of cytokinesis, implicating RalA as a
critical regulator of cell cycle progression.
PMID- 17028199
TI - Sialidase expression in activated human T lymphocytes influences production of
IFN-gamma.
AB - Sialidases influence cellular activity by removing terminal sialic acid from
glycoproteins and glycolipids. Four genetically distinct sialidases (Neu1-4) have
been identified in mammalian cells. In this study, we demonstrate that only
lysosomal Neu1 and plasma membrane-associated Neu3 are detected in freshly
isolated and activated human T lymphocytes. Activation of lymphocytes by exposure
to anti-CD3 and anti-CD28 IgG resulted in a ninefold increase in Neu1-specific
activity after growth of cells in culture for 5 days. In contrast, the activity
of Neu3 changed minimally in activated lymphocytes. The increase in Neu1 enzyme
activity correlated with increased synthesis of Neu1-specific mRNA. Neu1 was
present on the surface of freshly isolated and activated CD4 and CD8 T
lymphocytes, as determined by staining intact cells with anti-Neu1 IgG and
analysis by flow cytometry and by Western blot analysis of biotin-labeled cell
surface proteins. Cell surface Neu1 was found tightly associated with a subunit
of protective protein/cathepsin A (PPCA). Compared with freshly isolated
lymphocytes, activated cells expressed more surface binding sites for galactose
recognizing lectins Erythrina cristagalli (ECA) and Arachis hypogaea. Growth of
cells in the presence of sialidase inhibitors 2,3-dehydro-2-deoxy-N
acetylneuraminic acid or 4-guanidino-2-deoxy-2,3-dehydro-N-acetylneuraminic acid
resulted in a smaller increase in number of ECA-binding sites and a greater
amount of cell surface sialic acid in activated cells. Inhibition of sialidase
activity also resulted in reduced expression of IFN-gamma in activated cells. The
down-regulation of IFN-gamma occurred at the transcriptional level. Thus,
sialidase activity in activated T lymphocytes contributes to the hyposialylation
of specific cell surface glycoconjugates and to the production of IFN-gamma.
PMID- 17028200
TI - Regulatory T cell-mediated suppression: potential role of ICER.
AB - How regulatory T (TR) cells dampen T cell responses remains unclear. Multiple
modes of action have been proposed, including cell contact-dependent and/or
cytokine-dependent mechanisms. Suppression may involve direct contact between TR
cells and responder T cells. Alternatively, TR cells may act on dendritic cells
to reduce their ability to prime T cells by modulating costimulation, inducing
the secretion of suppressive cytokines or the increase of tryptophan metabolism.
Here, we review emerging, novel mechanisms involved in contact-dependent, TR
mediated suppression of IL-2 production in responder CD25- T lymphocytes and the
potential involvement of inducible cAMP early repressor (ICER) in this
suppression. Finally, cytokines such as TGF-beta and IL-10, produced by TR cells
or other cells, may exert local suppression, which can be conveyed by basic
mechanism(s) acting in a similar manner as contact-dependent, TR-mediated
suppression.
PMID- 17028201
TI - The role of CXC chemokine receptor 2 in Pseudomonas aeruginosa corneal infection.
AB - Pseudomonas is one of the leading causes of contact lens-related microbial
keratitis. Despite the use of antibiotics, the host inflammatory response
continues to cause damage to the cornea, which may lead to blindness. CXCR2
binding chemokines have been implicated in the pathogenesis of Pseudomonas
keratitis, and the exact role of this receptor remains to be elucidated. Corneas
of CXCR2 knockout and wild-type mice (Cmkar 2-/- and Cmkar 2+/+) were scratched,
and 2x10(6) CFU/mL Pseudomonas 6294 or 6206 was added to corneas. Twenty-four
hours postinfection, mice were killed, and eyes were harvested for enumeration of
bacteria, myeloperoxidase (MPO) levels, and inflammatory mediators. Cmkar 2-/-
had 20- to 100-fold more bacteria than Cmkar 2+/+ mice. There were no differences
in MPO levels between gene knockout and Cmkar 2+/+ mice. Histology revealed PMN
were restricted to the limbal area. Levels of CXCR2 chemokines (keratinocyte
derived chemokine and MIP-2) were elevated significantly in gene knockout mice. A
lack of CXCR2 leads to an inability to control bacterial numbers as a result of
the inability of PMN to reach the site of infection in the avascular cornea.
These results imply that CXCR2 is critical to the extravasation of neutrophils
into the avascular cornea.
PMID- 17028202
TI - The proteolytic function of the Arabidopsis 26S proteasome is required for
specifying leaf adaxial identity.
AB - Polarity formation is central to leaf morphogenesis, and several key genes that
function in adaxial-abaxial polarity establishment have been identified and
characterized extensively. We previously reported that Arabidopsis thaliana
ASYMMERTIC LEAVES1 (AS1) and AS2 are important in promoting leaf adaxial fates.
We obtained an as2 enhancer mutant, asymmetric leaves enhancer3 (ae3), which
demonstrated pleiotropic plant phenotypes, including a defective adaxial identity
in some leaves. The ae3 as2 double mutant displayed severely abaxialized leaves,
which were accompanied by elevated levels of leaf abaxial promoting genes
FILAMENTOUS FLOWER, YABBY3, KANADI1 (KAN1), and KAN2 and a reduced level of the
adaxial promoting gene REVOLUTA. We identified AE3, which encodes a putative 26S
proteasome subunit RPN8a. Furthermore, double mutant combinations of as2 with
other 26S subunit mutations, including rpt2a, rpt4a, rpt5a, rpn1a, rpn9a, pad1,
and pbe1, all displayed comparable phenotypes with those of ae3 as2, albeit with
varying phenotypic severity. Since these mutated genes encode subunits that are
located in different parts of the 26S proteasome, it is possible that the
proteolytic function of the 26S holoenzyme is involved in leaf polarity
formation. Together, our findings reveal that posttranslational regulation is
essential in proper leaf patterning.
PMID- 17028203
TI - The tomato NBARC-LRR protein Prf interacts with Pto kinase in vivo to regulate
specific plant immunity.
AB - Immunity in tomato (Solanum lycopersicum) to Pseudomonas syringae bacteria
expressing the effector proteins AvrPto and AvrPtoB requires both Pto kinase and
the NBARC-LRR (for nucleotide binding domain shared by Apaf-1, certain R gene
products, and CED-4 fused to C-terminal leucine-rich repeats) protein Prf. Pto
plays a direct role in effector recognition within the host cytoplasm, but the
role of Prf is unknown. We show that Pto and Prf are coincident in the signal
transduction pathway that controls ligand-independent signaling. Pto and Prf
associate in a coregulatory interaction that requires Pto kinase activity and N
myristoylation for signaling. Pto interacts with a unique Prf N-terminal domain
outside of the NBARC-LRR domain and resides in a high molecular weight
recognition complex dependent on the presence of Prf. In this complex, both Pto
and Prf contribute to specific recognition of AvrPtoB. The data suggest that the
role of Pto is confined to the regulation of Prf and that the bacterial effectors
have evolved to target this coregulatory molecular switch.
PMID- 17028204
TI - The Medicago truncatula CRE1 cytokinin receptor regulates lateral root
development and early symbiotic interaction with Sinorhizobium meliloti.
AB - Legumes develop different types of lateral organs from their primary root,
lateral roots and nodules, the latter depending on a symbiotic interaction with
Sinorhizobium meliloti. Phytohormones have been shown to function in the control
of these organogeneses. However, related signaling pathways have not been
identified in legumes. We cloned and characterized the expression of Medicago
truncatula genes encoding members of cytokinin signaling pathways. RNA
interference of the cytokinin receptor homolog Cytokinin Response1 (Mt CRE1) led
to cytokinin-insensitive roots, which showed an increased number of lateral roots
and a strong reduction in nodulation. Both the progression of S. meliloti
infection and nodule primordia formation were affected. We also identified two
cytokinin signaling response regulator genes, Mt RR1 and Mt RR4, which are
induced early during the symbiotic interaction. Induction of these genes by S.
meliloti infection is altered in mutants affected in the Nod factor signaling
pathway; conversely, cytokinin regulation of the early nodulin Nodule Inception1
(Mt NIN) depends on Mt CRE1. Hence, cytokinin signaling mediated by a single
receptor, Mt CRE1, leads to an opposite control of symbiotic nodule and lateral
root organogenesis. Mt NIN, Mt RR1, and Mt RR4 define a common pathway activated
during early S. meliloti interaction, allowing crosstalk between plant cytokinins
and bacterial Nod factors signals.
PMID- 17028205
TI - Loading of Arabidopsis centromeric histone CENH3 occurs mainly during G2 and
requires the presence of the histone fold domain.
AB - The centromeric histone H3 (CENH3) substitutes histone H3 within the nucleosomes
of active centromeres in all eukaryotes. CENH3 deposition at centromeres is
needed to assemble the kinetochore, a complex of conserved proteins responsible
for correct chromosome segregation during nuclear division. Histones of regular
nucleosomes are loaded during replication in S phase, while CENH3 deposition
deviates from this pattern in yeast, human, and Drosophila melanogaster cells.
Little is known about when and how CENH3 targets centromeric loci. Therefore, we
determined the location and quantity of recombinant enhanced yellow fluorescent
protein (EYFP)-CENH3 in mitotic root and endopolyploid leaf nuclei of transgenic
Arabidopsis thaliana cells. Our data indicate significant loading of A. thaliana
CENH3 during G2 (before splitting into sister kinetochores) rather than during
the S or M phase of the cell cycle. The histone fold domain of the C-terminal
part of CENH3 is sufficient to target A. thaliana centromeres. A. thaliana EYFP
CENH3 can recognize and target three different centromeric repeats of Arabidopsis
lyrata but not field bean (Vicia faba) centromeres.
PMID- 17028206
TI - A posttranslationally regulated protease, VheA, is involved in the liberation of
juveniles from parental spheroids in Volvox carteri.
AB - The lineage of volvocine algae includes unicellular Chlamydomonas and
multicellular Volvox in addition to their colonial relatives intermediate in size
and cell number. In an asexual life cycle, daughter cells of Chlamydomonas hatch
from parental cell walls soon after cell division, while Volvox juveniles are
released from parental spheroids after the completion of various developmental
events required for the survival of multicellular juveniles. Thus, heterochronic
change in the timing of hatching is considered to have played an important role
in the evolution of multicellularity in volvocine algae. To study the hatching
process in Volvox carteri, we purified a 125-kD Volvox hatching enzyme (VheA)
from a culture medium with enzymatic activity to degrade the parental spheroids.
The coding region of vheA contains a prodomain with a transmembrane segment, a
subtilisin-like Ser protease domain, and a functionally unknown domain, although
purified 125-kD VheA does not contain a prodomain. While 143-kD VheA with a
prodomain is synthesized long before the hatching stage, 125-kD VheA is released
into the culture medium during hatching due to cleavage processing at the site
between the prodomain and the subtilisin-like Ser protease domain, indicating
that posttranslational regulation is involved in the determination of the timing
of hatching.
PMID- 17028207
TI - Identification and characterization of components of a putative petunia S-locus F
box-containing E3 ligase complex involved in S-RNase-based self-incompatibility.
AB - Petunia inflata S-locus F-box (Pi SLF) is thought to function as a typical F-box
protein in ubiquitin-mediated protein degradation and, along with Skp1, Cullin-1,
and Rbx1, could compose an SCF complex mediating the degradation of nonself S
RNase but not self S-RNase. We isolated three P. inflata Skp1s (Pi SK1, -2, and
3), two Cullin-1s (Pi CUL1-C and -G), and an Rbx1 (Pi RBX1) cDNAs and found that
Pi CUL1-G did not interact with Pi RBX1 and that none of the three Pi SKs
interacted with Pi SLF(2). We also isolated a RING-HC protein, S-RNase Binding
Protein1 (Pi SBP1), almost identical to Petunia hybrida SBP1, which interacts
with Pi SLFs, S-RNases, Pi CUL1-G, and an E2 ubiquitin-conjugating enzyme,
suggesting that Pi CUL1-G, SBP1, and SLF may be components of a novel E3 ligase
complex, with Pi SBP1 playing the roles of Skp1 and Rbx1. S-RNases interact more
with nonself Pi SLFs than with self Pi SLFs, and Pi SLFs also interact more with
nonself S-RNases than with self S-RNases. Bacterially expressed S(1)-, S(2)-, and
S(3)-RNases are degraded by the 26S proteasomal pathway in a cell-free system,
albeit not in an S-allele-specific manner. Native glycosylated S(3)-RNase is not
degraded to any significant extent; however, deglycosylated S(3)-RNase is
degraded as efficiently as the bacterially expressed S-RNases. Finally, S-RNases
are ubiquitinated in pollen tube extracts, but whether this is mediated by the Pi
SLF-containing E3 complex is unknown.
PMID- 17028208
TI - Rice plastidial N-glycosylated nucleotide pyrophosphatase/phosphodiesterase is
transported from the ER-golgi to the chloroplast through the secretory pathway.
AB - A nucleotide pyrophosphatase/phosphodiesterase (NPP) activity that catalyzes the
hydrolytic breakdown of ADP-glucose (ADPG) has been shown to occur in the
plastidial compartment of both mono- and dicotyledonous plants. To learn more
about this enzyme, we purified two NPPs from rice (Oryza sativa) and barley
(Hordeum vulgare) seedlings. Both enzymes are glycosylated, since they bind to
concanavalin A, stain with periodic acid-Schiff reagent, and are digested by Endo
H. A complete rice NPP cDNA, designated as NPP1, was isolated, characterized, and
overexpressed in transgenic plants displaying high ADPG hydrolytic activity.
Databank searches revealed that NPP1 belongs to a functionally divergent group of
plant nucleotide hydrolases. NPP1 contains numerous N-glycosylation sites and a
cleavable hydrophobic signal sequence that does not match with the N-terminal
part of the mature protein. Both immunocytochemical analyses and confocal
fluorescence microscopy of rice cells expressing NPP1 fused with green
fluorescent protein (GFP) revealed that NPP1-GFP occurs in the plastidial
compartment. Brefeldin A treatment of NPP1-GFP-expressing cells prevented NPP1
GFP accumulation in the chloroplasts. Endo-H digestibility studies revealed that
both NPP1 and NPP1-GFP in the chloroplast are glycosylated. Collectively, these
data demonstrate the trafficking of glycosylated proteins from the endoplasmic
reticulum-Golgi system to the chloroplast in higher plants.
PMID- 17028209
TI - Mutants of Arabidopsis lacking starch branching enzyme II substitute plastidial
starch synthesis by cytoplasmic maltose accumulation.
AB - Three genes, BE1, BE2, and BE3, which potentially encode isoforms of starch
branching enzymes, have been found in the genome of Arabidopsis thaliana.
Although no impact on starch structure was observed in null be1 mutants,
modifications in amylopectin structure analogous to those of other branching
enzyme II mutants were detected in be2 and be3. No impact on starch content was
found in any of the single mutant lines. Moreover, three double mutant
combinations were produced (be1 be2, be1 be3, and be2 be3), and the impact of the
mutations on starch content and structure was analyzed. Our results suggest that
BE1 has no apparent function for the synthesis of starch in the leaves, as both
be1 be2 and be1 be3 double mutants display the same phenotype as be2 and be3
separately. However, starch synthesis was abolished in be2 be3, while high levels
of alpha-maltose were assayed in the cytosol. This result indicates that the
functions of both BE2 and BE3, which belong to class II starch branching enzymes,
are largely redundant in Arabidopsis. Moreover, we demonstrate that maltose
accumulation depends on the presence of an active ADP-glucose pyrophosphorylase
and that the cytosolic transglucosidase DISPROPORTIONATING ENZYME2, required for
maltose metabolization, is specific for beta-maltose.
PMID- 17028210
TI - Human immunodeficiency virus-infected patients with prior Pneumocystis pneumonia
exhibit increased serologic reactivity to several major surface glycoprotein
clones.
AB - Recombinant clones of the carboxyl terminus of the major surface glycoprotein
(MsgC) of Pneumocystis jirovecii are useful for analyzing serologic responses in
humans. However, there is no standardized set of antigens in general use, which
could lead to conflicting results. We have previously shown that human
immunodeficiency virus type 1 (HIV-1)-infected patients with prior Pneumocystis
pneumonia (PcP+) responded more frequently and more strongly to a clone of MsgC
than did HIV-1-infected patients without PcP (PcP-). Here we test three new
clones of MsgC to determine the effect of antigenic sequence variation on immune
reactivity in blood donors and HIV-infected patients previously analyzed for
reactivity to our original MsgC clone. In Western blot analyses, PcP+ patients
exhibited the highest frequency of reactivity to each MsgC clone, and the
frequency of reactivity with all four MsgC clones together was significantly
higher in sera from PcP+ patients than in sera from the other patient groups.
Furthermore, in an enzyme-linked immunosorbent assay we found that the PcP+
population had the highest level of reactivity to two of the four clones tested.
One of the new clones could distinguish between PcP+ and PcP- populations, and
two MsgC clones could distinguish blood donors from the other patient
populations. The results show that inherent differences in MsgC amino acid
sequence can affect recognition by antibodies independently of variations in
protein length or patient population, and the utility of a clone depends on its
sequence and on the populations tested.
PMID- 17028211
TI - Sequencing of the porB gene: a step toward a true characterization of Neisseria
meningitidis.
AB - Variations in class 2/3 (PorB) proteins form the basis for meningococcal
serotyping. Antibodies against these proteins are bactericidal, making serotyping
results useful not only for epidemiological surveillance of meningococcal disease
but also for identifying potential vaccine components. A total of 20 to 60% of
meningococcal B and C isolates from any given population are nontypeable (NT)
using a panel of monoclonal antibodies. To analyze the mechanisms responsible for
the nonserotypeability characteristic in Neisseria meningitidis, we (i)
established the nucleotide sequences of porB gene in 146 meningococcal strains
(95 not recognized by the serotyping panel), (ii) identified 18 new allelic
variants of the porB gene, (iii) correlated allelic variants with serotypes, (iv)
suggest the nontypeability characteristic in those 95 NT strains, and (v) reject
the possibility of variation in the levels of PorB expression.
PMID- 17028212
TI - Assessment of analysis of urinary pneumococcal antigen by immunochromatography
for etiologic diagnosis of community-acquired pneumonia in adults.
AB - The limitations of conventional microbiologic methods (CMM) for etiologic
diagnosis of community pneumococcal pneumonia have made faster diagnostic
techniques necessary. Our aim was to evaluate the usefulness of the
immunochromatography (ICT) technique for detecting urinary Streptococcus
pneumoniae antigen in the etiologic diagnosis of community-acquired pneumonias
(CAP). This was a prospective study on in-patients with CAP in a tertiary
hospital conducted from October 2000 to March 2004. Apart from using CMM to reach
an etiologic diagnosis, we determined pneumococcal antigen in concentrated urine
by ICT. We also determined the urinary pneumococcal antigen (UPA) content in
patients from two control groups to calculate the specificity of the technique.
One group was comprised of in-patients diagnosed with chronic obstructive
pulmonary disease (COPD) or asthma, with respiratory infection, and without
pneumonia; the other group included fractures. We studied 959 pneumonia patients
and determined UPA content in 911 (95%) of them. We diagnosed the etiology of 253
cases (28%) using CMM; S. pneumoniae was the most common etiologic agent (57
cases). ICT analysis was positive for 279 patients (31%). Using this technique,
the percentage of diagnoses of pneumococcal pneumonias increased by 26%, while
the overall etiologic diagnosis increased from 28 to 49%. The technique
sensitivity was 81%; the specificity oscillated between 80% in CAP with
nonpneumococcal etiology and 99% for patients with fractures without infections.
Determination of UPA is a rapid, simple analysis with good sensitivity and
specificity, which increased the percentage of etiologic diagnoses. Positive UPA
may persist in COPD patients with probable pneumococcal colonization or recent
pneumococcal infections.
PMID- 17028213
TI - Immune responses of elk to initial and booster vaccinations with Brucella abortus
strain RB51 or 19.
AB - Previous studies have suggested that currently available brucellosis vaccines
induce poor or no protection in elk (Cervus elaphus nelsoni). In this study, we
characterized the immunologic responses of elk after initial or booster
vaccination with Brucella abortus strains RB51 (SRB51) and 19 (S19). Elk were
vaccinated with saline or 10(10) CFU of SRB51 or S19 (n=seven animals/treatment)
and booster vaccinated with a similar dosage of the autologous vaccine at 65
weeks. Compared to nonvaccinates, elk vaccinated with SRB51 or S19 had greater
(P<0.05) antibody responses to SRB51 or S19 after initial vaccination and after
booster vaccination. Compared to nonvaccinated elk, greater (P<0.05)
proliferative responses to autologous antigen after initial vaccination occurred
at only a few sample times in SRB51 (6, 14, and 22 weeks) and S19 (22 weeks)
treatment groups. In general, proliferative responses of vaccinates to
nonautologous antigens did not differ (P>0.05) from the responses of
nonvaccinated elk. Gamma interferon production in response to autologous or
nonautologous Brucella antigens did not differ (P>0.05) between controls and
vaccinates after booster vaccination. Flow cytometric techniques suggested that
proliferation occurred more frequently in immunoglobulin M-positive cells, with
differences between vaccination and control treatments in CD4+ and CD8+ subset
proliferation detected only at 22 weeks after initial vaccination. After booster
vaccination, one technique ([3H]thymidine incorporation) suggested that
proliferative responses to SRB51 antigen, but not S19 antigen, were greater
(P<0.05) in vaccinates compared to the responses of nonvaccinates. However, in
general, flow cytometric and other techniques failed to detect significant
anamnestic responses to autologous or nonautologous Brucella antigens in S19 or
SRB51 vaccinates after booster vaccination. Although some cellular immune
responses were detected after initial or booster vaccination of elk with SRB51 or
S19, our data suggest that responses tend to be transient and much less robust
than previously reported in SRB51-vaccinated cattle (Bos taurus) or bison (Bison
bison). These data may explain why the vaccination of elk with S19 and SRB51
induces poor protection against brucellosis.
PMID- 17028214
TI - Amastin peptide-binding antibodies as biomarkers of active human visceral
leishmaniasis.
AB - Amastin surface proteins belong to a large family of developmentally regulated
proteins comprising up to 45 members that have recently been discovered in the
genus Leishmania and are highly similar to the amastin proteins in Trypanosoma
cruzi. All members of the amastin gene family contain a highly conserved 11-amino
acid (aa) signature at the N terminus, which is unique to the amastin proteins
and to the Trypanosomatidae family. Recent studies have demonstrated that this
region is highly protective in a mouse model. The goal of the present study was
to evaluate the potential of the 50-aa N-terminal domain of amastin proteins
harboring the conserved 11-aa amastin signature peptide as a relevant immune
biomarker of cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). We
report here the amastin-binding total immunoglobulins (IgG) and/or IgG subclasses
in the sera of patients at different stages of CL (n=90) and VL (n=41). In CL
cases, there is no significant difference in seroreactivities between active,
recovered, and nonhealed cases. However, the amastin peptide-reactive antibodies
were present at high titers in 19 of 20 sera collected from patients with active
VL compared to sera from patients recovered from VL and asymptomatic cases of VL.
These data suggest that the amastin signature peptide could represent a relevant
biomarker for the serodiagnosis of VL and, most importantly, that it could permit
differentiation among the different stages of the disease.
PMID- 17028215
TI - Induction of long-term lipopolysaccharide tolerance by an agonistic monoclonal
antibody to the toll-like receptor 4/MD-2 complex.
AB - We have established an agonistic monoclonal antibody, UT12, that induces
stimulatory signals comparable to those induced by lipopolysaccharide (LPS)
through Toll-like receptor 4 and MD-2. UT12 activated nuclear factor kappaB and
induced the production of proinflammatory cytokines such as tumor necrosis factor
alpha (TNF-alpha) and interleukin-6 (IL-6) in peritoneal exudative cells. In
addition, mice injected with UT12 rapidly fell into endotoxin shock concomitant
with the augmentation of serum TNF-alpha and IL-6 levels, followed by death
within 12 h. On the other hand, when the mice were pretreated with a sublethal
dose of UT12, the mice survived the subsequent lethal LPS challenges, with
significant suppression of serum TNF-alpha and IL-6, indicating that UT12 induced
tolerance against LPS. This effect of UT12 was maintained for at least 9 days. In
contrast, the tolerance induced by LPS continued for less than 3 days. These
results illuminate a novel potential therapeutic strategy for endotoxin shock by
the use of monoclonal antibodies against the Toll-like receptor 4/MD-2 complex.
PMID- 17028216
TI - Identification and characterization of a major cell wall-associated iron
regulated envelope protein (Irep-28) in Mycobacterium tuberculosis.
AB - Iron limitation and the expression of mycobactin and carboxymycobactin by
Mycobacterium tuberculosis are known. Here, we report how iron regulated the
coordinate expression of these two siderophores and a 28-kDa cell wall-associated
iron-regulated protein (Irep-28). Irep-28 is identified as the DNA-binding HU
homologue HupB protein (hupB [Rv2986c]). Antibodies to this protein were detected
in sera from tuberculosis patients. The location of the protein in the cell wall
makes it a potential drug target.
PMID- 17028217
TI - Comparison of the proteosomes and antigenicities of secreted and cellular
proteins produced by Mycobacterium paratuberculosis.
AB - The protein expression profiles and antigenicities of both culture filtrates (CF)
and cellular extracts (CE) of Mycobacterium paratuberculosis were compared by
sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), one
dimensional electrophoresis (1-DE) and 2-DE immunoblotting, and enzyme-linked
immunosorbent assay (ELISA). The CF proteins were harvested from supernatants of
stationary-phase liquid cultures and concentrated by size exclusion filtration.
The CE proteins were extracted by mechanical disruption of cells using glass
beads and a high-speed agitator. Analysis of SDS-PAGE gels showed that the
majority of CF proteins had low molecular masses (<50 kDa), whereas CE protein
mass ranged more evenly over a broader range up to 100 kDa. By 2-DE, CF proteins
had a narrow array of pI values, with most being between pH 4.0 and 5.5; CE
proteins spanned pI values from pH 4.0 to 7.0. The antigenicities of CF and CE
proteins were first determined by 1-DE and 2-DE immunoblotting with serum from a
cow naturally infected with M. paratuberculosis. The serum reacted strongly to
more proteins in the CF than the CE. Sera from 444 infected and 412 uninfected
cattle were tested by ELISA with CF and CE as solid-phase antigens. Receiver
operator characteristic curve analysis of the ELISA results showed a
significantly greater area under the curve for CF compared to CE (P<0.05). A high
degree of variability in protein binding patterns was shown with 1-DE immunoblot
analysis with 31 sera from M. paratuberculosis-infected cattle. Collectively,
these results indicate that serologic tests for bovine paratuberculosis may be
improved by using proteins derived from CF instead of CE. To maximize the
diagnostic sensitivity of serologic tests, multiple proteins will be required.
Even so, a CF ELISA may not be able to detect all M. paratuberculosis-infected
cattle, in particular those in the early stages of infection that have yet to
mount an antibody response.
PMID- 17028218
TI - Analysis of antibody response in humans to the type A OspC loop 5 domain and
assessment of the potential utility of the loop 5 epitope in Lyme disease vaccine
development.
AB - The OspC protein of Borrelia burgdorferi is an immunodominant antigen. Here we
demonstrate that the loop 5 domain of type A OspC is surface exposed, elicits
bactericidal antibody in mice, and is antigenic in humans. The data suggest that
loop 5 may be suitable for inclusion in a polyvalent, chimeric OspC vaccinogen.
PMID- 17028219
TI - Limited diagnostic capacities of two commercial assays for the detection of
Leptospira immunoglobulin M antibodies in Laos.
AB - The diagnostic utility of immunochromatographic (Leptotek) and enzyme-linked
immunosorbent assay (ELISA; Panbio) tests for the detection of Leptospira
immunoglobulin M antibodies was assessed in febrile adults admitted in Vientiane,
Laos. Both tests demonstrated poor diagnostic accuracy using admission serum
(Leptotek sensitivity of 47.3% and specificity of 75.5%: ELISA sensitivity of
60.9% and specificity of 65.6%) compared to the Leptospira "gold standard"
microscopic agglutination test.
PMID- 17028221
TI - Cell-mediated immune responses to smallpox vaccination.
AB - We report that vaccine dilution (1:1 or 1:10) and previous vaccinia virus
vaccination status had no significant effect on cell-mediated immune responses
(i.e., the immediate vaccinia virus-specific gamma interferon-producing T-cell
response measured by enzyme-linked immunospot assay) 1 month after smallpox
vaccination (Lancy-Vaxina; Berna Biotech, Switzerland).
PMID- 17028220
TI - Serologic evaluation of patients from Missouri with erythema migrans-like skin
lesions with the C6 Lyme test.
AB - Southern tick-associated rash illness (STARI), also known as Masters disease,
affects people predominantly in the Southeast and South Central United States.
These patients exhibit skin lesions that resemble erythema migrans (EM), the
characteristic skin lesion in early Lyme disease. The etiology of STARI remains
unknown, and no serologic test is available to aid in its diagnosis. The C6 Lyme
enzyme-linked immunosorbent assay was used to evaluate coded serum specimens from
patients with STARI at two laboratory sites. The specimens tested at one site
consisted of acute- and convalescent-phase samples that were obtained from nine
STARI patients from Missouri and from one patient with documented Borrelia
lonestari infection who acquired this infection in either North Carolina or
Maryland. All of these samples were C6 negative. Seventy acute- or convalescent
phase specimens from 63 STARI patients from Missouri were C6 tested at the second
site. All but one of these STARI specimens were also negative. In contrast, of
nine acute- and nine convalescent-phase serum specimens obtained from culture
confirmed Lyme disease patients with EM from New York state, seven were C6
positive at the acute stage, and eight were positive at convalescence. The C6
test is negative in patients with STARI, providing further evidence that B.
burgdorferi is not the etiologic agent of this disease.
PMID- 17028222
TI - High levels of serum thromboxane B2 are generated during human pulmonary
dirofilariosis.
AB - The canine parasite Dirofilaria immitis can infect humans. Patients with
pulmonary dirofilariosis develop significantly higher thromboxane B2 levels than
healthy individuals living in areas where dirofilariosis is endemic and in areas
where dirofilariosis is not endemic. The possible role of Wolbachia bacteria in
the appearance of this eicosanoid is discussed.
PMID- 17028223
TI - Change in substrate preference of Streptomyces aminopeptidase through
modification of the environment around the substrate binding site.
AB - We attempted to alter the substrate preference of aminopeptidase from
Streptomyces septatus TH-2 (SSAP). Because Asp198 and Phe221 of SSAP are located
in the substrate binding site, we screened 2,000 mutant enzymes with D198X/F221X
mutations. By carrying out this examination, we obtained two enzymes; one
specifically hydrolyzed an arginyl derivative, and the other specifically
hydrolyzed a cystinyl derivative (65- and 12.5-fold higher k(cat) values for
hydrolysis of p-nitroanilide derivatives than those of the wild type,
respectively).
PMID- 17028224
TI - Studies of the extracellular glycocalyx of the anaerobic cellulolytic bacterium
Ruminococcus albus 7.
AB - Anaerobic cellulolytic bacteria are thought to adhere to cellulose via several
mechanisms, including production of a glycocalyx containing extracellular
polymeric substances (EPS). As the compositions and structures of these
glycocalyces have not been elucidated, variable-pressure scanning electron
microscopy (VP-SEM) and chemical analysis were used to characterize the
glycocalyx of the ruminal bacterium Ruminococcus albus strain 7. VP-SEM revealed
that growth of this strain was accompanied by the formation of thin cellular
extensions that allowed the bacterium to adhere to cellulose, followed by
formation of a ramifying network that interconnected individual cells to one
another and to the unraveling cellulose microfibrils. Extraction of 48-h-old
whole-culture pellets (bacterial cells plus glycocalyx [G] plus residual
cellulose [C]) with 0.1 N NaOH released carbohydrate and protein in a ratio of
1:5. Boiling of the cellulose fermentation residue in a neutral detergent
solution removed almost all of the adherent cells and protein while retaining a
residual network of adhering noncellular material. Trifluoroacetic acid
hydrolysis of this residue (G plus C) released primarily glucose, along with
substantial amounts of xylose and mannose, but only traces of galactose, the most
abundant sugar in most characterized bacterial exopolysaccharides. Linkage
analysis and characterization by nuclear magnetic resonance suggested that most
of the glucosyl units were not present as partially degraded cellulose.
Calculations suggested that the energy demand for synthesis of the nonprotein
fraction of EPS by this organism represents only a small fraction (<4%) of the
anabolic ATP expenditure of the bacterium.
PMID- 17028225
TI - Quantification and stability of human adenoviruses and polyomavirus JCPyV in
wastewater matrices.
AB - Human adenoviruses (HAdV) and human polyomavirus JCPyV have been previously
proposed as indicators of fecal viral contamination in the environment. Different
wastewater matrices have been analyzed by applying real-time quantitative PCR
procedures for the presence, quantity, and stability of a wide diversity of
excreted HAdV and JCPyV. High quantities of HAdV and JCPyV were detected in
sewage, effluent wastewater, sludge, and biosolid samples. Both viruses showed
high stability in urban sewage. These results confirm the suitability of both
viruses as indicators of human fecal viral pollution.
PMID- 17028226
TI - Diversity and significance of mold species in Norwegian drinking water.
AB - In order to determine the occurrence, distribution, and significance of mold
species in groundwater- and surface water-derived drinking water in Norway, molds
isolated from 273 water samples were identified. Samples of raw water, treated
water, and water from private homes and hospital installations were analyzed by
incubation of 100-ml membrane-filtered samples on dichloran-18% glycerol agar.
The total count (number of CFU per 100 ml) of fungal species and the species
diversity within each sample were determined. The identification of mold species
was based on morphological and molecular methods. In total, 94 mold species
belonging to 30 genera were identified. The mycobiota was dominated by species of
Penicillium, Trichoderma, and Aspergillus, with some of them occurring throughout
the drinking water system. Several of the same species as isolated from water may
have the potential to cause allergic reactions or disease in humans. Other
species are common contaminants of food and beverages, and some may cause
unwanted changes in the taste or smell of water. The present results indicate
that the mycobiota of water should be considered when the microbiological safety
and quality of drinking water are assessed. In fact, molds in drinking water
should possibly be included in the Norwegian water supply and drinking water
regulations.
PMID- 17028227
TI - Longitudinal analysis of tick densities and Borrelia, Anaplasma, and Ehrlichia
infections of Ixodes ricinus ticks in different habitat areas in The Netherlands.
AB - From 2000 to 2004, ticks were collected by dragging a blanket in four habitat
areas in The Netherlands: dunes, heather, forest, and a city park. Tick densities
were calculated, and infection with Borrelia burgdorferi and Anaplasma and
Ehrlichia species was investigated by reverse line blot analysis. The lowest tick
density was observed in the heather area (1 to 8/100 m2). In the oak forest and
city park, the tick densities ranged from 26 to 45/100 m2. The highest tick
density was found in the dune area (139 to 551/100 m2). The infection rates
varied significantly for the four study areas and years, ranging from 0.8 to 11.
5% for Borrelia spp. and 1 to 16% for Ehrlichia or Anaplasma
(Ehrlichia/Anaplasma) spp. Borrelia infection rates were highest in the dunes,
followed by the forest, the city park, and heather area. In contrast,
Ehrlichia/Anaplasma was found most often in the forest and less often in the city
park. The following Borrelia species were found: Borrelia sensu lato strains not
identified to the species level (2.5%), B. afzelii (2.5%), B. valaisiana (0.9%),
B. burgdorferi sensu stricto (0.13%), and B. garinii (0.13%). For
Ehrlichia/Anaplasma species, Ehrlichia and Anaplasma spp. not identified to the
species level (2.5%), Anaplasma schotti variant (3.5%), Anaplasma phagocytophilum
variant (0.3%), and Ehrlichia canis (0.19%) were found. E. canis is reported for
the first time in ticks in The Netherlands in this study. Borrelia lusitaniae,
Ehrlichia chaffeensis, and the human granylocytic anaplasmosis agent were not
detected. About 1.6% of the ticks were infected with both Borrelia and
Ehrlichia/Anaplasma, which was higher than the frequency predicted from the
individual infection rates, suggesting hosts with multiple infections or a
possible selective advantage of coinfection.
PMID- 17028228
TI - A yeast platform for the production of single-chain antibody-green fluorescent
protein fusions.
AB - Fusion proteins comprised of a binding domain and green fluorescent protein (GFP)
have the potential to act as one-step binding reagents. In this study, eight
single-chain antibodies (scFv) and one single-chain T-cell receptor (scTCR) were
secreted as fusions to GFP using a Saccharomyces cerevisiae expression system.
Fusion protein secretion levels ranged over 3 orders of magnitude, from 4
microg/liter to 4 mg/liter, and correlated well with the secretion levels of the
unfused scFv/scTCR. Three fusion types with various linker lengths and fusion
orientations were tested for each scFv/scTCR. Although the fusion protein
secretion levels were not significantly affected by the nature of the fusion
construct, the properties of the fusion protein were clearly influenced. The
fluorescence yield per fusion molecule was increased by separating the scFv/scTCR
and GFP with an extended (GGGGS)3 linker, and fusions with scFv/scTCR at the
carboxy-terminus were more resistant to degradation. By evaluating leader
sequence processing and using GFP fluorescence to track intracellular processing,
it was determined that the majority of fusion protein synthesized by the yeast
was not secreted and in most cases was accumulating in an immature, although
active, endoplasmic-reticulum (ER)-processed form. This contrasted with unfused
scFv, which accumulated in both immature ER-processed and mature post-Golgi
forms. The results indicated that yeast can be used as an effective host for the
secretion of scFv/scTCR-GFP fusion proteins and that as a result of intracellular
secretory bottlenecks, there is considerable yeast secretory capacity remaining
to be exploited.
PMID- 17028229
TI - Can Anopheles gambiae be infected with Wolbachia pipientis? Insights from an in
vitro system.
AB - Wolbachia pipientis are maternally inherited endosymbionts associated with
cytoplasmic incompatibility, a potential mechanism to drive transgenic traits
into Anopheles populations for malaria control. W. pipientis infections are
common in many mosquito genera but have never been observed in any Anopheles
species, leading to the hypothesis that Anopheles mosquitoes are incapable of
harboring infection. We used an in vitro system to evaluate the ability of
Anopheles gambiae cells to harbor diverse W. pipientis infections. We
successfully established W. pipientis infections (strains wRi and wAlbB) in the
immunocompetent Anopheles gambiae cell line Sua5B. Infection was confirmed by
PCR, antibiotic curing, DNA sequencing, and direct observation using fluorescence
in situ hybridization. The infections were maintained at high passage rates for
>30 passages. Our results indicate that there is no intrinsic genetic block to W.
pipientis infection in A. gambiae cells, suggesting that establishment of in vivo
W. pipientis infections in Anopheles mosquitoes may be feasible.
PMID- 17028230
TI - Isolation and molecular characterization of chitinase-deficient Bacillus
licheniformis strains capable of deproteinization of shrimp shell waste to obtain
highly viscous chitin.
AB - Proteolytic but chitinase-deficient microbial cultures were isolated from shrimp
shell waste and characterized. The most efficient isolate was found to be a mixed
culture consisting of two Bacillus licheniformis strains, which were first
determined microscopically and physiologically. Molecular characterization was
carried out by sequencing the 16S rRNA gene of both strains. According to the
residual protein and ash content, the chitin obtained by fermentation of such a
mixed culture was found to be comparable to a commercially available, chemically
processed product. However, the strikingly high viscosity (80 versus 10 mPa of
the commercially available sample) indicates its superior quality. The two
strains differed in colony morphology and in their secretion capabilities for
degradative extracellular enzymes. Sequencing of the loci encoding amylase,
cellulase, chitinases, and proteases, as well as the degS/degU operon, which is
instrumental in the regulation of degradative enzymes, and the pga operon, which
is responsible for polyglutamic acid production, revealed no differences.
However, a frameshift mutation in chiA, encoding a chitinase, was validated for
both strains, providing an explanation for the ascertained absence of
chitinolytic activities and the concomitant possibility of producing highly
viscous chitin in a fermentational deproteinization process.
PMID- 17028232
TI - Rainfall-induced release of fecal coliforms and other manure constituents:
comparison and modeling.
AB - Modeling release of fecal coliforms is an important component of fate and
transport simulations related to environmental water quality. Manure constituents
other than fecal coliforms may serve as natural tracers of fecal contamination
provided that their release from manure to runoff is similar to the fecal
coliform release. The objectives of this work were to compare release of fecal
coliforms (FC), chloride (Cl-), organic carbon (OC), and water-soluble phosphorus
(P) from dissolving manure and to assess the performance of three models in
describing the observed release. Bovine manure was applied on 0.5- by 0.3-m bare
and vegetated subplots with 20% slope on sandy loam and clay loam soils.
Concentrations of Cl-, FC, OC, and P were measured in runoff collected from
troughs at the edges of the subplots at 5-min intervals during 1-h rainfall
simulations. The one-parametric exponential model and two-parametric Vadas
Kleinman-Sharpley model and Bradford-Schijven model were fitted to the data. The
Bradford-Schijven model had uncorrelated parameters, one of which was linearly
related to the irrigation rate, and another parameter reflected the presence or
the absence of vegetation. Kinetics of the FC release from manure was similar to
the release kinetics of P and OC. The Bradford-Schijven model is recommended to
simulate the release of manure constituents.
PMID- 17028231
TI - Escherichia coli biofilms formed under low-shear modeled microgravity in a ground
based system.
AB - Bacterial biofilms cause chronic diseases that are difficult to control. Since
biofilm formation in space is well documented and planktonic cells become more
resistant and virulent under modeled microgravity, it is important to determine
the effect of this gravity condition on biofilms. Inclusion of glass microcarrier
beads of appropriate dimensions and density with medium and inoculum, in vessels
specially designed to permit ground-based investigations into aspects of low
shear modeled microgravity (LSMMG), facilitated these studies. Mathematical
modeling of microcarrier behavior based on experimental conditions demonstrated
that they satisfied the criteria for LSMMG conditions. Experimental observations
confirmed that the microcarrier trajectory in the LSMMG vessel concurred with the
predicted model. At 24 h, the LSMMG Escherichia coli biofilms were thicker than
their normal-gravity counterparts and exhibited increased resistance to the
general stressors salt and ethanol and to two antibiotics (penicillin and
chloramphenicol). Biofilms of a mutant of E. coli, deficient in sigma(s), were
impaired in developing LSMMG-conferred resistance to the general stressors but
not to the antibiotics, indicating two separate pathways of LSMMG-conferred
resistance.
PMID- 17028233
TI - Evidence for the ubiquity of mixotrophic bacteria in the upper ocean:
implications and consequences.
PMID- 17028234
TI - Identification of novel Cryptosporidium genotypes from avian hosts.
AB - A total of 430 avian-derived fecal specimens were randomly collected from
selected Western Australian commercial aviaries, poultry farms, hatcheries,
wildlife parks, and the Perth Zoo and screened for the presence of
Cryptosporidium by PCR. Of these, 27 Cryptosporidium-positive isolates were
detected, characterized, and compared with 11 avian-derived isolates from the
Czech Republic at the 18S rRNA and actin gene loci. Sequence and phylogenetic
analysis identified four genetically distinct genotypes, avian genotypes I to IV,
from various avian hosts. In addition, the host range for Cryptosporidium galli
was extended. Cryptosporidium muris and Cryptosporidium andersoni were also
identified in a tawny frogmouth and a quail-crested wood partridge, respectively.
PMID- 17028235
TI - Identification of a putative operon involved in fructooligosaccharide utilization
by Lactobacillus paracasei.
AB - The growth and activity of some Lactobacillus and Bifidobacterium strains are
stimulated by the presence of nondigestible fructooligosaccharides (FOS), which
are selectively fermented by specific intestinal bacteria. Consumption of FOS,
therefore, enriches for those bacteria that possess metabolic pathways necessary
for FOS metabolism. In this study, a DNA microarray consisting of 7,680 random
genomic library fragments of Lactobacillus paracasei 1195 was used to examine
genes involved in the utilization of FOS in this organism. Differential
expression profiles between cells grown on FOS and those grown on glucose
provided a basis for identifying genes specifically induced by FOS. Several of
the FOS-induced genes shared sequence identity with genes encoding beta
fructosidases and components of phosphoenolpyruvate-dependent phosphotransferase
systems (PTS). These genes were organized in a putative operon, designated the
fos operon, that may play an essential role in FOS utilization. The complete
7,631-bp nucleotide sequence of the putative fos operon was determined and
consists of fosABCDXE genes, which encode a putative fructose/mannose PTS
(FosABCDX) and a beta-fructosidase precursor (FosE). The latter contains an N
terminal signal peptide sequence and cell wall sorting signals at the C-terminal
region, suggesting its localization at the cell wall. Inactivation of the fosE
gene led to impaired growth on FOS and other beta-fructose-linked carbohydrates.
Transcriptional analysis by reverse transcriptase PCR suggested that fosABCDXE
was cotranscribed as a single mRNA during growth on FOS. Expression array
analysis revealed that when glucose was added to FOS-grown cells, transcription
of the FOS-induced genes was repressed, indicating that FOS metabolism is subject
to catabolite regulation.
PMID- 17028236
TI - Multilocus sequence typing supports the hypothesis that cow- and human-associated
Salmonella isolates represent distinct and overlapping populations.
AB - A collection of 179 human and 156 bovine clinical Salmonella isolates obtained
from across New York state over the course of 1 year was characterized using
serotyping and a multilocus sequence typing (MLST) scheme based on the sequencing
of three genes (fimA, manB, and mdh). The 335 isolates were differentiated into
52 serotypes and 72 sequence types (STs). Analyses of bovine isolates collected
on different farms over time indicated that specific subtypes can persist over
time on a given farm; in particular, a number of farms showed evidence for the
persistence of a specific Salmonella enterica serotype Newport sequence type.
Serotypes and STs were not randomly distributed among human and bovine isolates,
and selected serotypes and STs were associated exclusively with either human or
bovine sources. A number of common STs were geographically widespread. For
example, ST6, which includes isolates representing serotype Typhimurium as well
as the emerging serotype 4,5,12:i:-, was found among human and bovine isolates in
a number of counties in New York state. Phylogenetic analyses supported the
possibility that serotype 4,5,12:i:- is closely related to Salmonella serotype
Typhimurium. Salmonella serotype Newport was found to represent two distinct
evolutionary lineages that differ in their frequencies among human and bovine
isolates. A number of Salmonella isolates carried two copies of manB (33
isolates) or showed small deletion events in fimA (nine isolates); these
duplication and deletion events may provide mechanisms for the rapid
diversification of Salmonella surface molecules. We conclude that the combined
use of an economical three-gene MLST scheme and serotyping can provide
considerable new insights into the evolution and transmission of Salmonella.
PMID- 17028237
TI - Molecular detection of epiphytic Acaryochloris spp. on marine macroalgae.
AB - A molecular method for detecting the epiphyte community on marine macroalgae was
developed by using PCR-denaturing gradient gel electrophoresis. Selective
amplification of 16S rRNA gene fragments from either cyanobacteria or algal
plastids improved the detection of minor epiphytes. Two phylotypes of
Acaryochloris, a chlorophyll d-containing cyanobacterium, were found not only on
red macroalgae but also on green and brown macroalgae.
PMID- 17028238
TI - Bacterial community structure in the hyperarid core of the Atacama Desert, Chile.
AB - Soils from the hyperarid Atacama Desert of northern Chile were sampled along an
east-west elevational transect (23.75 to 24.70 degrees S) through the driest
sector to compare the relative structure of bacterial communities. Analysis of
denaturing gradient gel electrophoresis (DGGE) profiles from each of the samples
revealed that microbial communities from the extreme hyperarid core of the desert
clustered separately from all of the remaining communities. Bands sequenced from
DGGE profiles of two samples taken at a 22-month interval from this core region
revealed the presence of similar populations dominated by bacteria from the
Gemmatimonadetes and Planctomycetes phyla.
PMID- 17028239
TI - Intracellular accumulation of trehalose protects Lactococcus lactis from freeze
drying damage and bile toxicity and increases gastric acid resistance.
AB - Interleukin-10 (IL-10) is a promising candidate for the treatment of inflammatory
bowel disease. Intragastric administration of Lactococcus lactis genetically
modified to secrete IL-10 in situ in the intestine was shown to be effective in
healing and preventing chronic colitis in mice. However, its use in humans is
hindered by the sensitivity of L. lactis to freeze-drying and its poor survival
in the gastrointestinal tract. We expressed the trehalose synthesizing genes from
Escherichia coli under control of the nisin-inducible promoter in L. lactis.
Induced cells accumulated intracellular trehalose and retained nearly 100%
viability after freeze-drying, together with a markedly prolonged shelf life.
Remarkably, cells producing trehalose were resistant to bile, and their viability
in human gastric juice was enhanced. None of these effects were seen with
exogenously added trehalose. Trehalose accumulation did not interfere with IL-10
secretion or with therapeutic efficacy in murine colitis. The newly acquired
properties should enable a larger proportion of the administered bacteria to
reach the gastrointestinal tract in a bioactive form, providing a means for more
effective mucosal delivery of therapeutics.
PMID- 17028241
TI - Activity of a second Trypanosoma brucei hexokinase is controlled by an 18-amino
acid C-terminal tail.
AB - Trypanosoma brucei expresses two hexokinases that are 98% identical, namely,
TbHK1 and TbHK2. Homozygous null TbHK2-/- procyclic-form parasites exhibit an
increased doubling time, a change in cell morphology, and, surprisingly, a
twofold increase in cellular hexokinase activity. Recombinant TbHK1 enzymatic
activity is similar to that of other hexokinases, with apparent Km values for
glucose and ATP of 0.09 +/- 0.02 mM and 0.28 +/- 0.1 mM, respectively. The k(cat)
value for TbHK1 is 2.9 x 10(4) min(-1). TbHK1 can use mannose, fructose, 2
deoxyglucose, and glucosamine as substrates. In addition, TbHK1 is inhibited by
fatty acids, with lauric, myristic, and palmitic acids being the most potent
(with 50% inhibitory concentrations of 75.8, 78.4, and 62.4 microM,
respectively). In contrast to TbHK1, recombinant TbHK2 lacks detectable enzymatic
activity. Seven of the 10 amino acid differences between TbHK1 and TbHK2 lie
within the C-terminal 18 amino acids of the polypeptides. Modeling of the
proteins maps the C-terminal tails near the interdomain cleft of the enzyme that
participates in the conformational change of the enzyme upon substrate binding.
Replacing the last 18 amino acids of TbHK2 with the corresponding residues of
TbHK1 yields an active recombinant protein with kinetic properties similar to
those of TbHK1. Conversely, replacing the C-terminal tail of TbHK1 with the TbHK2
tail inactivates the enzyme. These findings suggest that the C-terminal tail of
TbHK1 is important for hexokinase activity. The altered C-terminal tail of TbHK2,
along with the phenotype of the knockout parasites, suggests a distinct function
for the protein.
PMID- 17028242
TI - The illness trajectory of elderly cancer patients across cultures: SIOG position
paper.
AB - BACKGROUND: Due to the aging of the population, cancer has become a health
priority worldwide. While the number of elderly cancer patients is rapidly
increasing, many barriers still exist to their effective management. Compared
with their younger counterparts, the elderly are less likely to receive optimal
medical, psychological and spiritual treatment provided in a culturally competent
manner. DESIGN: The scanty literature on cultural competence in elderly cancer
patients has been reviewed. Additional material has been selected based on the
authors' clinical research in medical oncology and psycho-oncology, and on their
scholarly work in anthropology and bioethics. RESULTS: The aging process is a
synergistic product of biological, behavioral and social issues within a cultural
context. Knowledge about how older people understand, perceive and experience
their illness trajectory and make choices is essential to the planning and
delivering of effective cancer care. CONCLUSION: This position paper of the SIOG
Task Force on Cultural Competence in the Elderly creates awareness of the
influence of culture in geriatric oncology. Negotiating cross-cultural issues in
geriatric oncology helps managing possible conflicts between patients, families
and physicians over differing health care values, beliefs, or practices. Possible
areas of future scholarly investigation and clinical research are identified.
PMID- 17028240
TI - Reciprocal nuclear shuttling of two antagonizing Zn finger proteins modulates Tup
family corepressor function to repress chromatin remodeling.
AB - The Schizosaccharomyces pombe global corepressors Tup11 and Tup12, which are
orthologs of Saccharomyces cerevisiae Tup1, are involved in glucose-dependent
transcriptional repression and chromatin alteration of the fbp1+ gene. The fbp1+
promoter contains two regulatory elements, UAS1 and UAS2, one of which (UAS2)
serves as a binding site for two antagonizing C2H2 Zn finger transcription
factors, the Rst2 activator and the Scr1 repressor. In this study, we analyzed
the role of Tup proteins and Scr1 in chromatin remodeling at fbp1+ during glucose
repression. We found that Scr1, cooperating with Tup11 and Tup12, functions to
maintain the chromatin of the fbp1+ promoter in a transcriptionally inactive
state under glucose-rich conditions. Consistent with this notion, Scr1 is quickly
exported from the nucleus to the cytoplasm at the initial stage of derepression,
immediately after glucose starvation, at which time Rst2 is known to be imported
into the nucleus. In addition, chromatin immunoprecipitation assays revealed a
switching of Scr1 to Rst2 bound at UAS2 during glucose derepression. On the other
hand, Tup11 and Tup12 persist in the nucleus and bind to the fbp1+ promoter under
both derepressed and repressed conditions. These observations suggest that Tup1
like proteins recruited to the fbp1+ promoter are controlled by either of two
antagonizing C2H2 Zn finger proteins. We propose that the actions of Tup11 and
Tup12 are regulated by reciprocal nuclear shuttling of the two antagonizing Zn
finger proteins in response to the extracellular glucose concentration. This
notion provides new insights into the molecular mechanisms of the Tup family
corepressors in gene regulation.
PMID- 17028243
TI - Which benefit from adding gemcitabine to vinorelbine in elderly (>or=70 years)
women with metastatic breast cancer? Early interruption of a phase II study.
AB - BACKGROUND: Since vinorelbine and gemcitabine are both active in breast cancer
with moderate toxicity, in 2002 we started a phase II trial with a combination
regimen in elderly patients. PATIENTS AND METHODS: To evaluate complete plus
partial response rates and toxicity of first-line vinorelbine 25 mg/m2 plus
gemcitabine 1000 mg/m2 on days 1 and 8, every 3 weeks, in women>or=70 years with
advanced breast cancer and measurable lesions. All patients underwent
multidimensional geriatric assessment before enrollment. A two-step design was
applied, and the trial would be completed if an overall response rate>or=30% was
obtained with a grade 3-grade 4 (G3-G4) toxicity rateor=70
years outside the setting of controlled clinical trials.
PMID- 17028244
TI - Concurrent chemoradiotherapy with twice weekly paclitaxel and cisplatin followed
by esophagectomy for locally advanced esophageal cancer.
AB - BACKGROUND: To test the feasibility of incorporating a twice-weekly paclitaxel
(Taxol) and cisplatin regimen into concurrent chemoradiotherapy (CCRT), followed
by surgery, for patients with locally advanced esophageal cancer. PATIENTS AND
METHODS: Patients with operable T3N0-1M0 or T1-3N1M0 esophageal cancer were
enrolled. The CCRT regimen included paclitaxel (35 mg/m2 1 h on days 1 and
4/week), cisplatin (15 mg/m2 1 h on days 2 and 5/week), and radiotherapy (2 Gy on
days 1-5/week). When the accumulated radiation dose reached 40 Gy, the
feasibility of esophagectomy was evaluated in all patients. In patients for whom
esophagectomy was not feasible, CCRT was continued to a dose of 60 Gy. RESULTS:
The majority of 97 patients enrolled had squamous cell carcinoma on histology
(95%) and T3N1 disease by endoscopic ultrasonographic staging (90%). All patients
received CCRT to 40 Gy. Sixty-one patients underwent surgery, and 26 patients
continued definitive CCRT to 60 Gy. The intention-to-treat pathological complete
response rate was 25% [24/97, 95% confidence interval (CI) 16-33]. At a median
follow-up of 25.3 months, the median progression-free and overall survival was
15.6 and 28.8 months, respectively. The most common grade 3/4 toxic effects were
leukopenia (30%), thrombocytopenia (10%), and diarrhea (15%). CONCLUSIONS: CCRT
with a twice-weekly paclitaxel and cisplatin regimen followed by esophagectomy is
an active treatment of locally advanced esophageal cancer.
PMID- 17028245
TI - The extracellular cAMP-adenosine pathway significantly contributes to the in vivo
production of adenosine.
AB - The extracellular cAMP-adenosine pathway is the cellular egress of cAMP followed
by extracellular conversion of cAMP to adenosine by the sequential actions of
ecto-phosphodiesterase and ecto-5'-nucleotidase. Although detailed studies in
isolated organs, tissues, and cells provide evidence for an extracellular cAMP
adenosine pathway, whether this mechanism contributes significantly to adenosine
production in vivo is unclear. 1,3-Dipropyl-8-p-sulfophenylxanthine is restricted
to the extracellular compartment due to a negative charge at physiological pH
and, at high concentrations (> or =0.1 mM), blocks ecto-phosphodiesterase. Here,
we show that administration of 1,3-dipropyl-8-p-sulfophenylxanthine at a dose
that provided concentrations in plasma and urine of approximately 0.3 and 6 mM,
respectively, inhibited urinary adenosine excretion. In Sprague-Dawley rats i.v.,
1,3-dipropyl-8-p-sulfophenylxanthine (10 mg + 0.15 mg/min) significantly
decreased by 48 and 39% the urinary excretion of adenosine (from 3.57 +/- 0.38 to
1.87 +/- 0.14 nmol/30 min; p = 0.0003) and the ratio of urinary adenosine to cAMP
(from 0.93 +/- 0.08 to 0.57 +/- 0.06; p = 0.0044), respectively, without altering
blood pressure, renal blood flow, or glomerular filtration rate. Although 1,3
dipropyl-8-p-sulfophenylxanthine transiently increased urine volume and sodium
excretion, these effects subsided, yet adenosine excretion remained reduced.
Thus, changes in systemic and renal hemodynamics and excretory function could not
account for the effects of 1,3-dipropyl-8-p-sulfophenylxanthine on adenosine
excretion. Additional experiments showed that 1,3-dipropyl-8-p
sulfophenylxanthine, as in Sprague-Dawley rats, significantly attenuated
adenosine excretion and the ratio of urinary adenosine to cAMP in both Wistar
Kyoto rats and spontaneously hypertensive rats. We conclude that the
extracellular cAMP-adenosine pathway significantly contributes to the in vivo
production of adenosine.
PMID- 17028246
TI - The FLIP-side of Fas signaling.
PMID- 17028247
TI - A phase I study of in vitro expanded natural killer T cells in patients with
advanced and recurrent non-small cell lung cancer.
AB - PURPOSE: Human Valpha24 natural killer T (Valpha24 NKT) cells bearing an
invariant Valpha24JalphaQ antigen receptor are activated by a glicolipid ligand
alpha-galactosylceramide (alphaGalCer; KRN7000) in a CD1d-dependent manner. The
human Valpha24 NKT cells activated with alphaGalCer and interleukin-2 have been
shown to produce large amounts of cytokines, such as IFN-gamma, and also exerting
a potent killing activity against various tumor cell lines. We did a phase I
study with autologous activated Valpha24 NKT cell therapy. EXPERIMENTAL DESIGN:
Patients with advanced or recurrent non-small cell lung cancer received i.v.
injections of activated Valpha24 NKT cells (level 1: 1 x 10(7)/m2 and level 2: 5
x 10(7)/m2) to test the safety, feasibility, and clinical response of this
therapeutic strategy. Immunomonitoring was also done in all cases. RESULTS: Six
patients were enrolled in this study. No severe adverse events were observed
during this study in any patients. After the first and second injection of
activated Valpha24 NKT cells, an increased number of peripheral blood Valpha24
NKT cells was observed in two of three cases receiving a level 2 dose of
activated Valpha24 NKT cells. The number of IFN-gamma-producing cells in
peripheral blood mononuclear cells increased after the administration of
activated Valpha24 NKT cells in all three cases receiving the level 2 dose. No
patient was found to meet the criteria for either a partial or a complete
response. CONCLUSIONS: The clinical trial with activated Valpha24 NKT cell
administration was well tolerated and carried out safely with minor adverse
events even in patients with advanced diseases.
PMID- 17028248
TI - PrP genotype progression in flocks participating in the National Scrapie Plan for
Great Britain.
AB - The National Scrapie Plan (NSP) for Great Britain is a voluntary scheme that,
through PrP genotype testing and restricted breeding, aims to reduce the risk of
scrapie in the national sheep flock. To gauge the progress in member flocks and
within breeds, the genotype profile of successive crops of ram lambs was
monitored between 2002 and 2004. In each of the 11 most frequently sampled
breeds, the proportion of ram lambs testing in the most resistant genotype
category (NSP type 1: ARR/ARR) increased, and there was a reduction in the
proportion of genotypes associated with the highest disease risk, that is X/VRQ,
where X is an allele other than ARR. Changes in the proportion of ram lambs
testing for ARR-heterozygous genotypes (NSP type 2: ARR/X, where X is not VRQ)
appeared to be influenced by whether the sheep were hill breeds or non-hill
breeds. In each of six frequently sampled hill breeds these genotypes expanded,
in relative terms, whereas they declined in four of five prominent
lowland/crossing breeds. The proportion of ram lambs that carried neither ARR nor
VRQ (NSP type 3) declined consistently in the top 11 breeds, but there was little
change in the ARR/VRQ genotype (NSP type 4). Among individual flocks that had ram
lambs tested in all three years 2002 to 2004, the majority experienced an
increase in the proportion testing ARR/ARR, and of those that had VRQ ram lambs
in 2002, most recorded a decrease in their frequency by 2004.
PMID- 17028249
TI - Effects of two diets on the haematology, plasma chemistry and intestinal flora of
budgerigars (Melopsittacus undulatus).
AB - Two groups of 22 budgerigars (Melopsittacus undulatus) were housed for 12 months
under identical conditions. One group was fed a commercial seed mixture plus
carrots and a mineral supplement, and the other group was fed a commercially
formulated diet plus carrots. Samples of blood and faeces were collected
initially and after three, six, nine and 12 months. There were no significant
differences between the haematological values of the two groups. The group fed
the seed mixture had significantly higher concentrations of glucose, albumin,
triglycerides and uric acid, and higher activity of aspartate aminotransferase,
but the values were within the published reference ranges for normal birds. There
were no significant differences between the faecal samples from the two groups,
except that the fungus Macrorhabdus ornithogaster was identified in 48.3 per cent
of the samples from the group fed the commercially formulated diet but from only
3.4 per cent of the samples from the group fed the seed mixture.
PMID- 17028250
TI - Metallic foreign bodies in the tongues of 16 horses.
AB - The history, clinical signs, results of diagnostic imaging, treatment methods and
outcome of 16 adult horses with a metallic foreign body in the tongue are
reviewed. All the horses had a swollen tongue, they salivated excessively and
were partially to completely anorexic. Less common clinical signs were fever, an
enlarged and painful intermandibular space, dysphagia, unilateral tongue
paralysis and halitosis. Most of the horses had shown clinical signs for less
than 24 hours. The foreign bodies were diagnosed by oral examination, radiography
and ultrasonography; they were removed from the tongue of four of the horses
during the initial oral examination, and were removed surgically from nine
others; the other three horses were treated medically without attempts being made
to extract the foreign bodies. Twelve of the bodies were small pieces of wire and
one was a hypodermic needle. All the horses received a combination of
antimicrobial and non-steroidal anti-inflammatory drugs and they all made an
uneventful recovery. Feeding hay and the use of cable-framed tractor tyres as
feeders were commonly associated with the cases.
PMID- 17028251
TI - Low-dose dexamethasone test with "inverse" results: a possible new pattern of
cortisol response.
PMID- 17028252
TI - Treatment of penile prolapse in horses using a modified Buhner suture technique.
PMID- 17028253
TI - Lower urinary tract obstruction in a Mediterranean spur-thighed tortoise (Testudo
graeca) with coxofemoral arthritis.
PMID- 17028254
TI - Primary orthostatic tremor in a Scottish deerhound.
PMID- 17028255
TI - Deaths in aviary birds associated with protozoal megaloschizonts.
PMID- 17028257
TI - Practitioners' views.
PMID- 17028258
TI - Treatment of ovine caseous lymphadenitis.
PMID- 17028259
TI - Pathophysiological correlates of two unique renal tubule lesions in rats with
intestinal resection.
AB - Rats with small bowel resection fed a high-oxalate diet develop extensive
deposition of calcium oxalate (CaOx) and calcium phosphate crystals in the kidney
after 4 mo. To explore the earliest sites of renal crystal deposition, rats
received either small bowel resection or transection and were then fed either
standard chow or a high-oxalate diet; perfusion-fixed renal tissue from five rats
in each group was examined by light microscopy at 2, 4, 8, and 12 wk. Rats fed
the high-oxalate diet developed birefringent microcrystals at the brush border of
proximal tubule cells, with or without cell damage; the lesion was most common in
rats with both resection and a high-oxalate diet (10/19 with the lesion) and was
significantly correlated with urine oxalate excretion (P < 0.001). Rats with
bowel resection fed normal chow had mild hyperoxaluria but high urine CaOx
supersaturation; four of these rats developed birefringent crystal deposition
with tubule plugging in inner medullary collecting ducts (IMCD). Two rats fed a
high-oxalate diet also developed this lesion, which was correlated with CaOx
supersaturation, but not oxalate excretion. Tissue was examined under oil
immersion, and tiny birefringent crystals were noted on the apical surface of
IMCD cells only in animals with IMCD crystal plugging. In one animal, IMCD
crystals were both birefringent and nonbirefringent, suggesting a mix of CaOx and
calcium phosphate. Overall, these animals demonstrate two distinct sites and
mechanisms of renal crystal deposition and may help elucidate renal lesions seen
in humans with enteric hyperoxaluria and stones.
PMID- 17028260
TI - Expression and functional characteristics of tubular transporters: P
glycoprotein, PEPT1, and PEPT2 in renal mass reduction and diabetes.
AB - Renal mass reduction is associated with a compromise in renal excretion, and thus
dosages of drugs need to be adjusted to avoid adverse reactions and to ensure
their effectiveness. A prototypic example is patients who had undergone
transplantation due to a variety of causes, including diabetic nephropathy; the
latter appears to be the major cause of renal failure requiring hemodialysis and
transplantation. Conceivably, hyperglycemia with reduced renal mass interferes in
the delivery of xenobiotics handled by various tubular transporters. In this
investigation, effect of renal mass reduction/hyperglycemia on gene and protein
expression of P-glycoprotein (Pgp), PEPT1, and PEPT2 was assessed. Also,
[H(3)]glycylsarcosine uptake, a prototype of dipeptide, was measured in various
groups of rats: sham-operated, uninephrectomized, streptozotocin-induced
diabetes, and diabetic + uninephrectomized. An increase in Pgp, PEPT1, and PEPT2
expression was observed in kidneys of uninephrectomy rats, the highest being in
the Pgp. Similarly, an increase was observed in diabetic rats who had undergone
uninephrectomy, although less than those with nephrectomy alone. No differences
were observed between sham-operated and diabetic groups. Increased uptake of
[H(3)]glycylsarcosine was also seen in uninephrectomised rats. A modest uptake
was observed in diabetic rats who had undergone uninephrectomy. The data suggest
that uninephrectomy induces an increase in the expression and activity of
transporters localized to renal tubular epithelial brush border. The fact that
upregulation and activity of the peptide transporters were less in kidneys of
diabetic animals who had undergone uninephrectomy compared with uninephrectomy
alone suggests that hyperglycemia interferes in their expression and activity
during the compensatory phase.
PMID- 17028261
TI - Epithelial repair is inhibited by an alpha(1,6)-fucose binding lectin.
AB - The effective repair of damage to the airway epithelium is essential to maintain
the ability to exclude airborne particulates and protect against potential
pathogens. Carbohydrates on the cell surface have an important role in cell-cell
and cell substrate interactions. Using a model of repair with airway epithelial
derived cells of the 16HBE 14o(-) cell line, we have examined the effect of the
Aleuria aurantia lectin (AAL), which binds very selectively to alpha(1,6)-linked
fucose residues. Addition of unconjugated or FITC-labeled AAL reduced the rate of
epithelial repair to approximately one-third of control values as measured by
image analysis while cell viability was maintained. Pulse labeling with AAL-FITC
for 30 min followed by incubation in AAL-free medium caused similar inhibition of
repair but could be reversed by addition of fucose up to 7 h after AAL removal.
By confocal microscopy, AAL binding was found to be on the apical, but not
basolateral, surfaces of cells, and internalization of the labeled lectin was
seen. Preincubation of the lectin with fucose prevented this effect. Ulex
europeaus I lectin, which is also fucose specific, resulted in similar binding to
the cells and internalization, but it did not affect the speed of the repair
process. We conclude that alpha(1,6)-fucose binding sites play an important role
in epithelial repair. Better understanding of this process will provide a deeper
insight into the crucial mechanisms of epithelial repair.
PMID- 17028262
TI - Prostaglandin E(2) inhibits collagen expression and proliferation in patient
derived normal lung fibroblasts via E prostanoid 2 receptor and cAMP signaling.
AB - Uncontrolled fibroblast activation is one of the hallmarks of fibrotic lung
disease. Prostaglandin E(2) (PGE(2)) has been shown to inhibit fibroblast
migration, proliferation, collagen deposition, and myofibroblast differentiation
in the lung. Understanding the mechanisms for these effects may provide insight
into the pathogenesis of fibrotic lung disease. Previous work has focused on
commercially available fibroblast cell lines derived from tissue whose precise
origin and histopathology are often unknown. Here, we sought to define the
mechanism of PGE(2) inhibition in patient-derived fibroblasts from peripheral
lung verified to be histologically normal. Fibroblasts were grown from explants
of resected lung, and proliferation and collagen I expression was determined
following treatment with PGE(2) or modulators of its receptors and downstream
signaling components. PGE(2) inhibited fibroblast proliferation by 33% and
collagen I expression by 62%. PGE(2) resulted in a 15-fold increase in
intracellular cAMP; other cAMP-elevating agents inhibited collagen I in a manner
similar to PGE(2). These effects were reproduced by butaprost, a PGE(2) analog
selective for the cAMP-coupled E prostanoid (EP) 2 receptor, but not by selective
EP3 or EP4 agonists. Fibroblasts expressed both major cAMP effectors, protein
kinase A (PKA) and exchange protein activated by cAMP-1 (Epac-1), but only a
selective PKA agonist was able to appreciably inhibit collagen I expression.
Treatment with okadaic acid, a phosphatase inhibitor, potentiated the effects of
PGE(2). Our data indicate that PGE(2) inhibits fibroblast activation in primary
lung fibroblasts via binding of EP2 receptor and production of cAMP; inhibition
of collagen I proceeds via activation of PKA.
PMID- 17028263
TI - Diesel exhaust particulate-induced activation of Stat3 requires activities of
EGFR and Src in airway epithelial cells.
AB - In vivo exposure to diesel exhaust particles (DEP) elicits acute inflammatory
responses in the lung characterized by inflammatory cell influx and elevated
expression of mediators such as cytokines and chemokines. Signal transducers and
activators of transcription (STAT) proteins are a family of cytoplasmic
transcription factors that are key transducers of signaling in response to
cytokine and growth factor stimulation. One member of the STAT family, Stat3, has
been implicated as a regulator of inflammation but has not been studied in regard
to DEP exposure. The results of this study show that DEP induces Stat3
phosphorylation as early as 1 h following stimulation and that phosphorylated
Stat3 translocates into the nucleus. Inhibition of epidermal growth factor
receptor (EGFR) and Src activities by the inhibitors PD-153035 and PP2,
respectively, abolished the activation of Stat3 by DEP, suggesting that Stat3
activation by DEP requires EGFR and Src kinase activation. The present study
suggests that oxidative stress induced by DEP may play a critical role in
activating EGFR signaling, as evidenced by the fact that pretreatment with
antioxidant prevented the activation of EGFR and Stat3. These findings
demonstrate that DEP inhalation can activate proinflammatory Stat3 signaling in
vitro.
PMID- 17028264
TI - Cell-based tissue engineering for lung regeneration.
AB - Emphysema is a chronic lung disease characterized by alveolar enlargement and
tissue loss. Tissue engineering represents an attractive potential for
regeneration of several organ systems. The complex three-dimensional
architectural structure of lung parenchyma requiring connections of alveolar
units to airways and the pulmonary circulation makes this strategy less
optimistic. In the present study, we used Gelfoam sponge as a scaffold material,
supplemented with fetal rat lung cells as progenitors, to explore the potential
application of cell-based tissue engineering for lung regeneration in adult rats.
After injection into lung parenchyma, the sponge showed porous structures similar
to alveolar units. It did not induce severe local inflammatory response. Fetal
lung cells in the sponge were able to survive in the adult lung for at least 35
days, determined by CMTMR [5-(and-6)-{[(4
chloromethyl)benzoyl]amino}tetramethylrhodamine] labeling. Proliferation of cells
within the sponge was demonstrated in vivo by bromodeoxyuridine (BrdU) labeling.
Cells formed "alveolar-like structures" at the border between the sponge and the
surrounding lung tissue with positive immunohistochemical staining for epithelial
and endothelial cells. Neovascularization of the sponge was demonstrated with
India ink perfusion. The sponge degraded after several months. This study
suggests that cell-based tissue engineering possesses the potential to regenerate
alveolar-like structures, an important step towards our ultimate goal of lung
regeneration.
PMID- 17028265
TI - Regulation of urokinase receptor expression by protein tyrosine phosphatases.
AB - Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play a major
role in several physiological processes such as cell migration, proliferation,
morphogenesis, and regulation of gene expression. Many of the biological
activities of uPA depend on its association with uPAR. uPAR expression and its
induction by uPA are regulated at the posttranscriptional level. Inhibition of
protein tyrosine phosphatase-mediated dephosphorylation by sodium orthovanadate
induces uPAR expression and, with uPA, additively induces cell surface uPAR
expression. Sodium orthovanadate induces uPAR by increasing uPAR mRNA in a time-
and concentration-dependent manner. Both sodium orthovanadate and uPA induce uPAR
mRNA stability, indicating that dephosphorylation could contribute to uPA-induced
posttranscriptional regulation of uPAR expression. Induction of the tyrosine
phosphatase SHP2 in Beas2B and H157 cells inhibits basal cell surface uPAR
expression and uPA-induced uPAR expression. Sodium orthovanadate also increases
uPAR expression by decreasing the interaction of a uPAR mRNA coding region
sequence with phosphoglycerate kinase (PGK) as well as by enhancing the
interaction between a uPAR mRNA 3' untranslated sequence with heterogeneous
nuclear ribonucleoprotein C (hnRNPC). On the contrary, overexpression of SHP2 in
Beas2B cells increased interaction of PGK with the uPAR mRNA coding region and
inhibited hnRNPC binding to the 3' untranslated sequence. These findings confirm
a novel mechanism by which uPAR expression of lung airway epithelial cells is
regulated at the level of mRNA stability by inhibition of protein tyrosine
phosphatase-mediated dephosphorylation of uPAR mRNA binding proteins and
demonstrate that the process involves SHP2.
PMID- 17028266
TI - Increased lung expansion alters lung growth but not alveolar epithelial cell
differentiation in newborn lambs.
AB - Although increased lung expansion markedly alters lung growth and epithelial cell
differentiation during fetal life, the effect of increasing lung expansion after
birth is unknown. We hypothesized that increased basal lung expansion, caused by
ventilating newborn lambs with a positive end-expiratory pressure (PEEP), would
stimulate lung growth and alter alveolar epithelial cell (AEC) proportions and
decrease surfactant protein mRNA levels. Two groups of lambs were sedated and
ventilated with either 0 cmH(2)O PEEP (controls, n = 5) or 10 cmH(2)O PEEP (n =
5) for 48 h beginning at 15 +/- 1 days after normal term birth. A further group
of nonventilated 2-wk-old lambs was used for comparison. We determined wet and
dry lung weights, DNA and protein content, a labeling index for proliferating
cells, surfactant protein mRNA expression, and proportions of AECs using electron
microscopy. Although ventilating lambs for 48 h with 10 cmH(2)O PEEP did not
affect total lung DNA or protein, it significantly increased the proportion of
proliferating cells in the lung when compared with nonventilated 2-wk-old
controls and lambs ventilated with 0 cmH(2)O PEEP (control: 2.6 +/- 0.5%; 0 PEEP:
1.9 +/- 0.3%; 10 PEEP: 3.5 +/- 0.3%). In contrast, no differences were observed
in AEC proportions or surfactant protein mRNA levels between either of the
ventilated groups. This study demonstrates that increases in end-expiratory lung
volumes, induced by the application of PEEP, lead to increased lung growth in
mechanically ventilated 2-wk-old lambs but do not alter the proportions of AECs.
PMID- 17028267
TI - Cyclic stretch induces PlGF expression in bronchial airway epithelial cells via
nitric oxide release.
AB - Mechanical strain of lung tissue is an important stimulus for the production of
growth factors that are critical for lung growth and development. However,
excessive mechanical strain, as may occur during mechanical ventilation, may
produce an increase in growth factors that may contribute to lung injury. We
hypothesized that mechanical strain of primary bronchial airway epithelial cells
(BAEpCs) induced the production of placental growth factor (PlGF), a member of
the VEGF family. BAEpCs were cultured on a deformable silicoelastic membrane and
exposed to different magnitudes of stretch. Stretch induced PlGF and nitric oxide
(NO) production that increased with increasing magnitude of stretch. Stretch also
induced PlGF and inducible NO synthase (iNOS) gene expression. The stretch
induced PlGF production and NO synthesis were attenuated by PD98059, a specific
mitogen-activated protein kinase kinase-1 and -2 inhibitor. Inhibition of NO
generation by l-NAME or l-NMMA or scavenging NO by carboxy-PTIO prevented stretch
mediated erk1/2 activation. In addition, in unstretched BAEpCs, exogenous NO
enhanced erk1/erk2 activation. Our data suggest that mechanical stretch of BAEpCs
induces iNOS expression and induces PlGF release in an erk1/2 activation
dependent manner.
PMID- 17028268
TI - Notch-1 regulates pulmonary neuroendocrine cell differentiation in cell lines and
in transgenic mice.
AB - The notch gene family encodes transmembrane receptors that regulate cell
differentiation by interacting with surface ligands on adjacent cells.
Previously, we demonstrated that tumor necrosis factor-alpha (TNF) induces
neuroendocrine (NE) cell differentiation in H82, but not H526, undifferentiated
small cell lung carcinoma lines. We now test the hypothesis that TNF mediates NE
cell differentiation in part by altering Notch gene expression. First, using RT
PCR, we determined that TNF treatment of H82, but not H526, transiently decreases
notch-1 mRNA in parallel with induction of gene expression for the NE-specific
marker DOPA decarboxylase (DDC). Second, we treated H82 and H526 with notch-1
antisense vs. sense oligodeoxynucleotides. Using quantitative RT-PCR and Western
analyses we demonstrate that DDC mRNA and protein are increased in H82 by notch-1
antisense, whereas notch-1 mRNA and activated Notch-1 protein are decreased. mRNA
for Hes1, a transcription factor downstream from activated Notch, is also
decreased by Notch-1 antisense in H82 but not H526. After 7 days of Notch-1
antisense treatment, neural cell adhesion molecule (NCAM) immunoreactivity is
induced in H82 but not H526. Third, we generated transgenic mice bearing notch-1
driven by the neural/NE-specific calcitonin promoter, which express activated
Notch-1 in developing lung epithelium. Newborn NotchCal mouse lungs have high
levels of hes1 mRNA, reflecting increased activated Notch, compared with wild
type. NotchCal lungs have decreased CGRP-positive NE cells, decreased protein
gene product 9.5 (PGP9.5)-positive NE cells, and decreased gastrin-releasing
peptide (GRP), CGRP, and DDC mRNA levels compared with normal littermates.
Cumulatively, these observations provide further support for a role for Notch-1
signaling in regulating pulmonary NE cell differentiation.
PMID- 17028269
TI - Population genetics and linkage analysis of loci within the FCT region of
Streptococcus pyogenes.
AB - The FCT regions of Streptococcus pyogenes strains encode a variety of cell wall
anchored surface proteins that bind the extracellular matrix of the human host
and/or give rise to pilus-like appendages. Strong linkage is evident between
transcription-regulatory loci positioned within the FCT and emm regions and the
emm pattern genotype marker for preferred infection of the throat or skin. These
findings provide a basis for the hypothesis that FCT region gene products
contribute to tissue-specific infection. In an initial series of steps to address
this possibility, the FCT regions of 13 strains underwent comparative sequence
analysis, the gene content of the FCT region was characterized for 113 strains
via PCR, and genetic linkage was assessed. A history of extensive recombination
within FCT regions was evident. The emm pattern D-defined skin specialist strains
were highly homogenous in their FCT region gene contents, whereas the emm pattern
A-C-defined throat specialist strains displayed a greater variety of forms. Most
pattern A-C strains harbored prtF1 (75%) but lacked cpa (75%). In contrast, the
majority of emm pattern D strains had cpa (92%) but lacked prtF1 (79%). Models
based on FCT and emm region genotypes revealed the most parsimonious pathways of
evolution. Using niche-determining candidate genes to infer phylogeny, emm
pattern E strains--the so-called generalists, which lack a strong tissue site
preference--occupied a transition zone separating most throat specialists from
skin specialists. Overall, population genetic analysis supports the possibility
that the FCT region gives rise to surface proteins that are largely necessary,
but not always sufficient, to confer tissue site preference for infection.
PMID- 17028270
TI - Time-resolved determination of the CcpA regulon of Lactococcus lactis subsp.
cremoris MG1363.
AB - Carbon catabolite control protein A (CcpA) is the main regulator involved in
carbon catabolite repression in gram-positive bacteria. Time series gene
expression analyses of Lactococcus lactis MG1363 and L. lactis MG1363DeltaccpA
using DNA microarrays were used to define the CcpA regulon of L. lactis. Based on
a comparison of the transcriptome data with putative CcpA binding motifs (cre
sites) in promoter sequences in the genome of L. lactis, 82 direct targets of
CcpA were predicted. The main differences in time-dependent expression of CcpA
regulated genes were differences between the exponential and transition growth
phases. Large effects were observed for carbon and nitrogen metabolic genes in
the exponential growth phase. Effects on nucleotide metabolism genes were
observed primarily in the transition phase. Analysis of the positions of putative
cre sites revealed that there is a link between either repression or activation
and the location of the cre site within the promoter region. Activation was
observed when putative cre sites were located upstream of the hexameric -35
sequence at an average position of -56.5 or further upstream with decrements of
10.5 bp. Repression was observed when the cre site was located in or downstream
of putative -35 and -10 sequences. The highest level of repression was observed
when the cre site was present at a defined side of the DNA helix relative to the
canonical -10 sequence. Gel retardation experiments, Northern blotting, and
enzyme assays showed that CcpA represses its own expression and activates the
expression of the divergently oriented prolidase-encoding pepQ gene, which
constitutes a link between regulation of carbon metabolism and regulation of
nitrogen metabolism.
PMID- 17028271
TI - The two-component regulatory system TCS08 is involved in cellobiose metabolism of
Streptococcus pneumoniae R6.
AB - The two-component system TCS08 is one of the regulatory systems that is important
for virulence of Streptococcus pneumoniae. In order to investigate the TCS08
regulon, we have analyzed transcription profiles of mutants derived from S.
pneumoniae R6 by microarray analysis. Since deletion mutants are often without a
significant phenotype, we constructed a mutation in the histidine kinase HK08,
T133P, in analogy to the phosphatase mutation T230P in the H box of the S.
pneumoniae CiaH kinase described recently (D. Zahner, K. Kaminski, M. van der
Linden, T. Mascher, M. Merai, and R. Hakenbeck, J. Mol. Microbiol. Biotechnol.
4:211-216, 2002). In addition, a deletion mutation was constructed in rr08,
encoding the cognate response regulator. The most heavily suppressed genes in the
hk08 mutant were spr0276 to spr0282, encoding a putative cellobiose
phosphoenolpyruvate sugar phosphotransferase system (PTS). Whereas the R6 Sm(r)
parent strain and the Deltarr08 mutant readily grew on cellobiose, the hk08
mutant and selected mutants with deletions in the PTS cluster did not, strongly
suggesting that TCS08 is involved in the catabolism of cellobiose. Homologues of
the TCS08 system were found in closely related streptococci and other gram
positive cocci. However, the genes spr0276 to spr0282, encoding the putative
cellobiose PTS, represent a genomic island in S. pneumoniae and homologues were
found in Streptococcus gordonii only, suggesting that this system might
contribute to the pathogenicity potential of the pneumococcus.
PMID- 17028272
TI - The gene cluster for agmatine catabolism of Enterococcus faecalis: study of
recombinant putrescine transcarbamylase and agmatine deiminase and a snapshot of
agmatine deiminase catalyzing its reaction.
AB - Enterococcus faecalis makes ATP from agmatine in three steps catalyzed by
agmatine deiminase (AgDI), putrescine transcarbamylase (PTC), and carbamate
kinase (CK). An antiporter exchanges putrescine for agmatine. We have cloned the
E. faecalis ef0732 and ef0734 genes of the reported gene cluster for agmatine
catabolism, overexpressed them in Escherichia coli, purified the products,
characterized them functionally as PTC and AgDI, and crystallized and X-ray
diffracted them. The 1.65-Angstroms-resolution structure of AgDI forming a
covalent adduct with an agmatine-derived amidine reactional intermediate is
described. We provide definitive identification of the gene cluster for agmatine
catabolism and confirm that ornithine is a genuine but poor PTC substrate,
suggesting that PTC (found here to be trimeric) evolved from ornithine
transcarbamylase. N-(Phosphonoacetyl)-putrescine was prepared and shown to
strongly (K(i) = 10 nM) and selectively inhibit PTC and to improve PTC
crystallization. We find that E. faecalis AgDI, which is committed to ATP
generation, closely resembles the AgDIs involved in making polyamines, suggesting
the recruitment of a polyamine-synthesizing AgDI into the AgDI pathway. The
arginine deiminase (ADI) pathway of arginine catabolism probably supplied the
genes for PTC and CK but not those for the agmatine/putrescine antiporter, and
thus the AgDI and ADI pathways are not related by a single "en bloc" duplication
event. The AgDI crystal structure reveals a tetramer with a five-blade propeller
subunit fold, proves that AgDI closely resembles ADI despite a lack of sequence
identity, and explains substrate affinity, selectivity, and Cys357-mediated
covalent catalysis. A three-tongued agmatine-triggered gating opens or blocks
access to the active center.
PMID- 17028273
TI - Lysophosphatidylethanolamine is a substrate for the short-chain alcohol
dehydrogenase SocA from Myxococcus xanthus.
AB - Short-chain alcohol dehydrogenases (SCADHs) synthesize a variety of intercellular
signals and other chemically diverse products. It is difficult to predict the
substrate of a SCADH on the basis of amino acid sequence homology, as the
substrates are not known for most SCADHs. In Myxococcus xanthus, the SCADH CsgA
is responsible for C signaling during fruiting body development, although the
mechanism is unclear. Overexpression of the SCADH SocA compensates for the lack
of CsgA and restores development and C signaling in csgA mutants. The potential
of SocA in generating the C signal enzymatically was explored by developing a
dehydrogenase assay-based screen to purify the SocA substrate(s). A SocA
substrate was extracted from M. xanthus cells with acidified ethyl acetate and
sequentially purified by solid-phase extraction on silica gel and by reverse
phase high-performance liquid chromatography. The fraction with the highest SocA
dehydrogenase activity contained the lysophospholipid 1-acyl 2-hydroxy-sn
glycerophosphoethanolamine (lyso-PE) as indicated by the fragment ions and a
phosphatidylethanolamine-specific neutral loss scan following liquid
chromatography coupled to mass spectrometry. The abundant lysophospholipid with
the mass m/z 450 (molecular ion [M-H]-) had a monounsaturated acyl chain with 16
carbons. SocA oxidizes lyso-PE containing either saturated or unsaturated fatty
acids but exhibits poor activity on l-alpha-glycerophosphorylethanolamine,
suggesting that an acyl chain is important for activity. Of the five different
head groups, only ethanolamine showed appreciable activity. The apparent Km and
Vmax for lyso-PE 18:1 were 116 microM and 875 micromol min(-1) mg(-1),
respectively. The catalytic efficiency (k(cat)/Km) was 1 x 10(8) M(-1) s(-1). The
proposed product, 1-acyloxy-3-(2-aminoethylphosphatyl) acetone was unstable, and
the fragmented products were unable to rescue csgA mutant development. The active
fraction from thin-layer chromatography also contained an unidentified SocA
substrate that had morphogenic properties.
PMID- 17028274
TI - Characterization of XynC from Bacillus subtilis subsp. subtilis strain 168 and
analysis of its role in depolymerization of glucuronoxylan.
AB - Secretion of xylanase activities by Bacillus subtilis 168 supports the
development of this well-defined genetic system for conversion of
methylglucuronoxylan (MeGAXn [where n represents the number of xylose residues])
in the hemicellulose component of lignocellulosics to biobased products. In
addition to the characterized glycosyl hydrolase family 11 (GH 11) endoxylanase
designated XynA, B. subtilis 168 secretes a second endoxylanase as the translated
product of the ynfF gene. This sequence shows remarkable homology to the GH 5
endoxylanase secreted by strains of Erwinia chrysanthemi. To determine its
properties and potential role in the depolymerization of MeGAXn, the ynfF gene
was cloned and overexpressed to provide an endoxylanase, designated XynC, which
was characterized with respect to substrate preference, kinetic properties, and
product formation. With different sources of MeGAXn as the substrate, the
specific activity increased with increasing methylglucuronosyl substitutions on
the beta-1,4-xylan chain. With MeGAXn from sweetgum as a preferred substrate,
XynC exhibited a Vmax of 59.9 units/mg XynC, a Km of 1.63 mg MeGAXn/ml, and a
k(cat) of 2,635/minute at pH 6.0 and 37 degrees C. Matrix-assisted laser
desorption ionization-time of flight mass spectrometry and 1H nuclear magnetic
resonance data revealed that each hydrolysis product has a single glucuronosyl
substitution penultimate to the reducing terminal xylose. This detailed analysis
of XynC from B. subtilis 168 defines the unique depolymerization process
catalyzed by the GH 5 endoxylanases. Based upon product analysis, B. subtilis 168
secretes both XynA and XynC. Expression of xynA was subject to MeGAXn induction;
xynC expression was constitutive with growth on different substrates. Translation
and secretion of both GH 11 and GH 5 endoxylanases by the fully sequenced and
genetically malleable B. subtilis 168 recommends this bacterium for the
introduction of genes required for the complete utilization of products of the
enzyme-catalyzed depolymerization of MeGAXn. B. subtilis may serve as a model
platform for development of gram-positive biocatalysts for conversion of
lignocellulosic materials to renewable fuels and chemicals.
PMID- 17028275
TI - Heme biosynthesis in Methanosarcina barkeri via a pathway involving two
methylation reactions.
AB - The methanogenic archaeon Methanosarcina barkeri synthesizes protoheme via
precorrin-2, which is formed from uroporphyrinogen III in two consecutive
methylation reactions utilizing S-adenosyl-L-methionine. The existence of this
pathway, previously exclusively found in the sulfate-reducing delta
proteobacterium Desulfovibrio vulgaris, was demonstrated for M. barkeri via the
incorporation of two methyl groups from methionine into protoheme.
PMID- 17028276
TI - nalD encodes a second repressor of the mexAB-oprM multidrug efflux operon of
Pseudomonas aeruginosa.
AB - The Pseudomonas aeruginosa nalD gene encodes a TetR family repressor with
homology to the SmeT and TtgR repressors of the smeDEF and ttgABC multidrug
efflux systems of Stenotrophomonas maltophilia and Pseudomonas putida,
respectively. A sequence upstream of mexAB-oprM and overlapping a second promoter
for this efflux system was very similar to the SmeT and TtgR operator sequences,
and NalD binding to this region was, in fact, demonstrated. Moreover, increased
expression from this promoter was seen in a nalD mutant, consistent with NalD
directly controlling mexAB-oprM expression from a second promoter.
PMID- 17028277
TI - RhlR expression in Pseudomonas aeruginosa is modulated by the Pseudomonas
quinolone signal via PhoB-dependent and -independent pathways.
AB - The expression of virulence determinants in Pseudomonas aeruginosa is
coordinately regulated in response to both the social environment--commonly
referred to as quorum sensing--and to environmental cues. In this study we have
dissected the various independent regulation levels for pyocyanin production,
which is influenced by the homoserine lactone- and Pseudomonas quinolone signal
(PQS)-mediated quorum-sensing systems as well as by iron and phosphate
availability. We demonstrate that the phosphate regulon is involved in the
transcriptional activation of rhlR and the augmentation of PQS and pyocyanin
production under phosphate limitation. However, we also observed an enhancement
of rhlR transcription under low-iron medium conditions and after the addition of
PQS that was independent of the phosphate regulon. These results highlight the
complexity of secondary metabolite production in P. aeruginosa via environmental
cues and the quorum-sensing system.
PMID- 17028278
TI - Overlapping and specialized functions of the molybdenum-dependent regulators MopA
and MopB in Rhodobacter capsulatus.
AB - The phototrophic purple bacterium Rhodobacter capsulatus encodes two similar but
functionally not identical molybdenum-dependent regulator proteins (MopA and
MopB), which are known to replace each other in repression of the modABC genes
(coding for an ABC-type high-affinity Mo transport system) and anfA (coding for
the transcriptional activator of Fe-nitrogenase genes). We identified further Mo
regulated (mor) genes coding for a putative ABC-type transport system of unknown
function (MorABC) and a putative Mo-binding protein (Mop). The genes coding for
MopA and the ModABC transporter form part of a single transcriptional unit, mopA
modABCD, as shown by reverse transcriptase PCR. Immediately upstream of mopA and
transcribed in the opposite direction is mopB. The genes coding for the putative
MorABC transporter belong to two divergently transcribed operons, morAB and morC.
Expression studies based on lacZ reporter gene fusions in mutant strains
defective for either MopA, MopB, or both revealed that the regulators substitute
for each other in Mo-dependent repression of morAB and morC. Specific Mo
dependent activation of the mop gene by MopA, but not MopB, was found to control
the putative Mo-binding protein. Both MopA and MopB are thought to bind to
conserved DNA sequences with dyad symmetry in the promoter regions of all target
genes. The positions of these so-called Mo boxes relative to the transcription
start sites (as determined by primer extension analyses) differed between Mo
repressed genes and the Mo-activated mop gene. DNA mobility shift assays showed
that MopA and MopB require molybdenum to bind to their target sites with high
affinity.
PMID- 17028279
TI - Mesorhizobium loti produces nodPQ-dependent sulfated cell surface
polysaccharides.
AB - Leguminous plants and bacteria from the family Rhizobiaceae form a symbiotic
relationship, which culminates in novel plant structures called root nodules. The
indeterminate symbiosis that forms between Sinorhizobium meliloti and alfalfa
requires biosynthesis of Nod factor, a beta-1,4-linked lipochitooligosaccharide
that contains an essential 6-O-sulfate modification. S. meliloti also produces
sulfated cell surface polysaccharides, such as lipopolysaccharide (LPS). The
physiological function of sulfated cell surface polysaccharides is unclear,
although mutants of S. meliloti with reduced LPS sulfation exhibit symbiotic
abnormalities. Using a bioinformatic approach, we identified a homolog of the S.
meliloti carbohydrate sulfotransferase, LpsS, in Mesorhizobium loti. M. loti
participates in a determinate symbiosis with the legume Lotus japonicus. We
showed that M. loti produces sulfated forms of LPS and capsular polysaccharide
(KPS). To investigate the physiological function of sulfated polysaccharides in
M. loti, we identified and disabled an M. loti homolog of the sulfate-activating
genes, nodPQ, which resulted in undetectable amounts of sulfated cell surface
polysaccharides and a cysteine auxotrophy. We concomitantly disabled an M. loti
cysH homolog, which disrupted cysteine biosynthesis without reducing cell surface
polysaccharide sulfation. Our experiments demonstrated that the nodPQ mutant, but
not the cysH mutant, showed an altered KPS structure and a diminished ability to
elicit nodules on its host legume, Lotus japonicus. Interestingly, the nodPQ
mutant also exhibited a more rapid growth rate and appeared to outcompete wild
type M. loti for nodule colonization. These results suggest that sulfated cell
surface polysaccharides are required for optimum nodule formation but limit
growth rate and nodule colonization in M. loti.
PMID- 17028280
TI - A homologue of the 3-oxoacyl-(acyl carrier protein) synthase III gene located in
the glycosylation island of Pseudomonas syringae pv. tabaci regulates virulence
factors via N-acyl homoserine lactone and fatty acid synthesis.
AB - Pseudomonas syringae pv. tabaci 6605 possesses a genetic region involved in
flagellin glycosylation. This region is composed of three open reading frames:
orf1, orf2, and orf3. Our previous study revealed that orf1 and orf2 encode
glycosyltransferases; on the other hand, orf3 has no role in posttranslational
modification of flagellin. Although the function of Orf3 remained unclear, an
orf3 deletion mutant (Deltaorf3 mutant) had reduced virulence on tobacco plants.
Orf3 shows significant homology to a 3-oxoacyl-(acyl carrier protein) synthase
III in the fatty acid elongation cycle. The Deltaorf3 mutant had a significantly
reduced ability to form acyl homoserine lactones (AHLs), which are quorum-sensing
molecules, suggesting that Orf3 is required for AHL synthesis. In comparison with
the wild-type strain, swarming motility, biosurfactant production, and tolerance
to H2O2 and antibiotics were enhanced in the Deltaorf3 mutant. A scanning
electron micrograph of inoculated bacteria on the tobacco leaf surface revealed
that there is little extracellular polymeric substance matrix surrounding the
cells in the Deltaorf3 mutant. The phenotypes of the Deltaorf3 mutant and an AHL
synthesis (DeltapsyI) mutant were similar, although the mutant-specific
characteristics were more extreme in the Deltaorf3 mutant. The swarming motility
of the Deltaorf3 mutant was greater than that of the DeltapsyI mutant. This was
attributed to the synergistic effects of the overproduction of biosurfactants
and/or alternative fatty acid metabolism in the Deltaorf3 mutant. Furthermore,
the amounts of iron and biosurfactant seem to be involved in biofilm development
under quorum-sensing regulation in P. syringae pv. tabaci 6605.
PMID- 17028281
TI - Rapid evolution of diminished transformability in Acinetobacter baylyi.
AB - The reason for genetic exchange remains a crucial question in evolutionary
biology. Acinetobacter baylyi strain ADP1 is a highly competent and
recombinogenic bacterium. We compared the parallel evolution of wild-type and
engineered noncompetent lineages of A. baylyi in the laboratory. If
transformability were to result in an evolutionary benefit, it was expected that
competent lineages would adapt more rapidly than noncompetent lineages. Instead,
regardless of competency, lineages adapted to the same extent under several
laboratory conditions. Furthermore, competent lineages repeatedly evolved a much
lower level of transformability. The loss of competency may be due to a selective
advantage or the irreversible transfer of loss-of-function alleles of genes
required for transformation within the competent population.
PMID- 17028282
TI - Cyclic di-GMP signaling in bacteria: recent advances and new puzzles.
PMID- 17028283
TI - Mycoplasma genitalium P140 and P110 cytadhesins are reciprocally stabilized and
required for cell adhesion and terminal-organelle development.
AB - Mycoplasma genitalium is a human pathogen that mediates cell adhesion by a
complex structure known as the attachment organelle. This structure is composed
of cytadhesins and cytadherence-associated proteins, but few data are available
about the specific role of these proteins in M. genitalium cytadherence. We have
deleted by homologous recombination the mg191 and mg192 genes from the MgPa
operon encoding the P140 and P110 cytadhesins. Molecular characterization of
these mutants has revealed a reciprocal posttranslational stabilization between
the two proteins. Loss of either P140 or P110 yields a hemadsorption-negative
phenotype and correlates with decreased or increased levels of cytoskeleton
related proteins MG386 and DnaK, respectively. Scanning electron microscopy
analysis reveals the absolute requirement of P140 and P110 for the proper
development of the attachment organelle. The phenotype described for these
mutants resembles that of the spontaneous class I and class II cytadherence
negative mutants [G. R. Mernaugh, S. F. Dallo, S. C. Holt, and J. B. Baseman,
Clin. Infect. Dis. 17(Suppl. 1):S69-S78, 1993], whose genetic basis remained
undetermined until now. Complementation assays and sequencing analysis
demonstrate that class I and class II mutants are the consequence of large
deletions affecting the mg192 and mg191-mg192 genes, respectively. These
deletions originated from single-recombination events involving sequences of the
MgPa operon and the MgPa island located immediately downstream. We also
demonstrate the translocation of MgPa sequences to a particular MgPa island by
double-crossover events. Based on these observations, we propose that in addition
to being a source of antigenic variation, MgPa islands could be also involved in
a general phase variation mechanism switching on and off, in a reversible or
irreversible way, the adhesion properties of M. genitalium.
PMID- 17028284
TI - Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and
nonribosomal peptide synthetase genes and down regulates virulence-associated
surface lipid synthesis.
AB - The Mycobacterium tuberculosis genome encodes 12 alternative sigma factors,
several of which regulate stress responses and are required for virulence in
animal models of acute infection. In this work we investigated M. tuberculosis
SigM, a member of the extracytoplasmic function subfamily of alternative sigma
factors. This sigma factor is expressed at low levels in vitro and does not
appear to function in stress response regulation. Instead, SigM positively
regulates genes required for the synthesis of surface or secreted molecules.
Among these are genes encoding two pairs of Esx secreted proteins, a multisubunit
nonribosomal peptide synthetase operon, and genes encoding two members of the
proline-proline-glutamate (PPE) family of proteins. Genes up regulated in a sigM
mutant strain include a different PPE gene, as well as several genes involved in
surface lipid synthesis. Among these are genes involved in synthesis of
phthiocerol dimycocerosate (PDIM), a surface lipid critical for virulence during
acute infection, and the kasA-kasB operon, which is required for mycolic acid
synthesis. Analysis of surface lipids showed that PDIM synthesis is increased in
a sigM-disrupted strain and is undetectable in a sigM overexpression strain.
These findings demonstrate that SigM positively and negatively regulates cell
surface and secreted molecules that are likely to function in host-pathogen
interactions.
PMID- 17028285
TI - Biosynthetic pathways of inositol and glycerol phosphodiesters used by the
hyperthermophile Archaeoglobus fulgidus in stress adaptation.
AB - Archaeoglobus fulgidus accumulates di-myo-inositol phosphate (DIP) and diglycerol
phosphate (DGP) in response to heat and osmotic stresses, respectively, and the
level of glycero-phospho-myo-inositol (GPI) increases primarily when the two
stresses are combined. In this work, the pathways for the biosynthesis of these
three compatible solutes were established based on the detection of the relevant
enzymatic activities and characterization of the intermediate metabolites by
nuclear magnetic resonance analysis. The synthesis of DIP proceeds from glucose-6
phosphate via four steps: (i) glucose-6-phosphate was converted into l-myo
inositol 1-phosphate by l-myo-inositol 1-phosphate synthase; (ii) l-myo-inositol
1-phosphate was activated to CDP-inositol at the expense of CTP; this is the
first demonstration of CDP-inositol synthesis in a biological system; (iii) CDP
inositol was coupled with l-myo-inositol 1-phosphate to yield a phosphorylated
intermediate, 1,1'-di-myo-inosityl phosphate 3-phosphate (DIPP); (iv) finally,
DIPP was dephosphorylated into DIP by the action of a phosphatase. The synthesis
of the two other polyol-phosphodiesters, DGP and GPI, proceeds via the
condensation of CDP-glycerol with the respective phosphorylated polyol, glycerol
3-phosphate for DGP and l-myo-inositol 1-phosphate for GPI, yielding the
respective phosphorylated intermediates, 1X,1'X-diglyceryl phosphate 3-phosphate
(DGPP) and 1-(1X-glyceryl) myo-inosityl phosphate 3-phosphate (GPIP), which are
subsequently dephosphorylated to form the final products. The results disclosed
here represent an important step toward the elucidation of the regulatory
mechanisms underlying the differential accumulation of these compounds in
response to heat and osmotic stresses.
PMID- 17028286
TI - The parsing of food reward.
PMID- 17028287
TI - Vagal afferents are essential for maximal resection-induced intestinal adaptive
growth in orally fed rats.
AB - Small bowel resection stimulates intestinal adaptive growth by a neuroendocrine
process thought to involve both sympathetic and parasympathetic innervation and
enterotrophic hormones such as glucagon-like peptide-2 (GLP-2). We investigated
whether capsaicin-sensitive vagal afferent neurons are essential for maximal
resection-induced intestinal growth. Rats received systemic or perivagal
capsaicin or ganglionectomy before 70% midjejunoileal resection or transection
and were fed orally or by total parenteral nutrition (TPN) for 7 days after
surgery. Growth of residual bowel was assessed by changes in mucosal mass,
protein, DNA, and histology. Both systemic and perivagal capsaicin significantly
attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein,
and DNA in rats fed orally. Villus height was significantly reduced in resected
rats given capsaicin compared with vehicle. Sucrase specific activity in jejunal
mucosa was not significantly different; ileal mucosal sucrase specific activity
was significantly increased by resection in capsaicin-treated rats. Capsaicin did
not alter the 57% increase in ileal proglucagon mRNA or the 150% increase in
plasma concentration of bioactive GLP-2 resulting from resection in orally fed
rats. Ablation of spinal/splanchnic innervation by ganglionectomy failed to
attenuate resection-induced adaptive growth. In TPN rats, capsaicin did not
attenuate resection-induced mucosal growth. We conclude that vagal afferents are
not essential for GLP-2 secretion when the ileum has direct contact with luminal
nutrients after resection. In summary, vagal afferent neurons are essential for
maximal resection-induced intestinal adaptation through a mechanism that appears
to involve stimulation by luminal nutrients.
PMID- 17028288
TI - Editorial: The SERM of my dreams.
PMID- 17028289
TI - Editorial: Mortality and renal disease in type 1 diabetes mellitus--progress
made, more to be done.
PMID- 17028290
TI - Editorial: Anti-Mullerian hormone: Cinderella finds new admirers.
PMID- 17028291
TI - Editorial: Metabolism lessons for survival: when adults and children are not
alike.
PMID- 17028292
TI - Understanding the presence and function of erythropoietin receptors on cancer
cells.
PMID- 17028293
TI - Do erythropoietin receptors on cancer cells explain unexpected clinical findings?
AB - PURPOSE: Recent reports suggest that cancer control may worsen if erythropoietin
is administered. We investigated whether erythropoietin receptor expression on
cancer cells may correlate with this unexpected finding. PATIENTS AND METHODS:
Cancer tissue from patients with advanced carcinoma of the head and neck (T3, T4,
or nodal involvement) and scheduled for radiotherapy was assayed retrospectively
for erythropoietin receptor expression by immunohistochemistry. Patients were
anemic and randomized to receive epoetin beta (300 U/kg) or placebo under double
blind conditions, given three times weekly starting 10 to 14 days before and
continuing throughout radiotherapy. We administered 60 Gy following complete
resection or 64 Gy subsequent to microscopically incomplete resection; 70 Gy were
given following macroscopically incomplete resection or for definitive
radiotherapy alone. We determined if the effect of epoetin beta on locoregional
progression-free survival was correlated with the expression of erythropoietin
receptors on cancer cells using a Cox proportional hazards regression model.
RESULTS: We studied 154 of 157 randomly assigned patients; 104 samples were
positive, and 50 were negative for receptor expression. Locoregional progression
free survival was substantially poorer if epoetin beta was administered to
patients positive for receptor expression compared with placebo (adjusted
relative risk, 2.07; 95% CI, 1.27 to 3.36; P < .01). In contrast, epoetin beta
did not impair outcome in receptor-negative patients (adjusted relative risk,
0.94; 95% CI, 0.47 to 1.90; P = .86). The difference in treatment associated
relative risks (2.07 v 0.94) was borderline statistically significant (P = .08).
CONCLUSION: Erythropoietin might adversely affect prognosis of head and neck
cancer patients if cancer cells express erythropoietin receptors.
PMID- 17028294
TI - Molecular and pathologic aspects of endometrial carcinogenesis.
AB - Endometrial cancer is the most common gynecological malignancy, with 41,000 new
cases projected in the United States for 2006. Two different clinicopathologic
subtypes are recognized: the estrogen-related (type I, endometrioid) and the non
estrogen-related types (type II, nonendometrioid such as papillary serous and
clear cell). The morphologic differences in these cancers are mirrored in their
molecular genetic profile with type I showing defects in DNA-mismatch repair and
mutations in PTEN, K-ras, and beta-catenin, and type II showing aneuploidy and
p53 mutations. This article reviews the genetic aspects of endometrial
carcinogenesis and progression. We will define the precursor lesion of type I
endometrioid cancer and the role of genetics and estrogen in its progression.
PMID- 17028295
TI - Elaborate petals in Australian Spermacoce (Rubiaceae) species: morphology,
ontogeny and function.
AB - BACKGROUND AND AIMS: Australian Spermacoce species display various types of
elaborate petals. Their precise morphology, ontogenetic origin, and function are
hitherto unknown. The aim of the present paper is to unravel the development and
nature of the diverse types of elaborate petals in Spermacoce through a floral
ontogenetic study. METHODS: The floral ontogeny of six species characterized by
different types of corolla appendages was studied by scanning electron microscopy
and light microscopy. In order to elucidate the possible functions of the
elaborate petals, field observations were conducted as well. KEY RESULTS:
Scanning electronmicrographs show that full-grown petals of Spermacoce lignosa,
S. phaeosperma and S. redacta bear appendages on their ventral side. Despite
their different appearance at anthesis, the appendages develop very similarly in
all three species. They are initiated at the same developmental stage and are
first visible as two arcs of primordia converging from the upper margins of the
petal towards its midvein and downwards. In S. brevidens, S. caudata and S.
erectiloba, the full-grown petals have two long, concave protuberances, which
develop from the tissue at both sides of the petal's mid-vein. In these three
species, initiation of appendages on the ventral side of the petals is also
observed, but they are hardly visible on the mature petals. The two types of
elaborate petals tightly enclose the anthers, both in bud and during most of the
flowering period. CONCLUSIONS: Among Australian Spermacoce species, two types of
elaborate petals can be distinguished. The former hypothesis that the two types
of elaborate petals are essentially homologous is here rejected. Field
investigations point out that the elaborate petals might play a role in the
pollination biology of the species.
PMID- 17028297
TI - alpha-Pinene inhibits growth and induces oxidative stress in roots.
AB - BACKGROUND AND AIMS: Determining the mode of action of allelochemicals is one of
the challenging aspects in allelopathic studies. Recently, allelochemicals have
been proposed to cause oxidative stress in target tissue and induce an
antioxidant mechanism. alpha-Pinene, one of the common monoterpenoids emitted
from several aromatic plants including forest trees, is known for its growth
inhibitory activity. However, its mechanism of action remains unexplored. The aim
of the present study was to determine the inhibitory effect of alpha-pinene on
root growth and generation of reactive oxygen species, as indicators of oxidative
stress and changes in activities of antioxidant enzymes. METHODS: Effects of
alpha-pinene on early root growth were studied in five test species, Cassia
occidentalis, Amaranthus viridis, Triticum aestivum, Pisum sativum and Cicer
arietinum. Electrolyte leakage, lipid peroxidation, hydrogen peroxide generation,
proline accumulation, and activities of the enzymes superoxide dismutase (SOD),
ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT) and
glutathione reductase (GR) were studied in roots of C. occidentalis. KEY RESULTS:
alpha-Pinene inhibited the radicle growth of all the test species. Exposure of C.
occidentalis roots to alpha-pinene enhanced solute leakage, and increased levels
of malondialdehyde, proline and hydrogen peroxide, indicating lipid peroxidation
and induction of oxidative stress. Activities of the antioxidant enzymes SOD,
CAT, GPX, APX and GR were significantly elevated, thereby indicating the enhanced
generation of reactive oxygen species (ROS) upon alpha-pinene exposure. Increased
levels of scavenging enzymes indicates their induction as a secondary defence
mechanism in response to alpha-pinene. CONCLUSIONS: It is concluded that alpha
pinene inhibits early root growth and causes oxidative damage in root tissue
through enhanced generation of ROS, as indicated by increased lipid peroxidation,
disruption of membrane integrity and elevated antioxidant enzyme levels.
PMID- 17028296
TI - Drought, abscisic acid and transpiration rate effects on the regulation of PIP
aquaporin gene expression and abundance in Phaseolus vulgaris plants.
AB - BACKGROUND AND AIMS: Drought causes a decline of root hydraulic conductance,
which aside from embolisms, is governed ultimately by aquaporins. Multiple
factors probably regulate aquaporin expression, abundance and activity in leaf
and root tissues during drought; among these are the leaf transpiration rate,
leaf water status, abscisic acid (ABA) and soil water content. Here a study is
made of how these factors could influence the response of aquaporin to drought.
METHODS: Three plasma membrane intrinsic proteins (PIPs) or aquaporins were
cloned from Phaseolus vulgaris plants and their expression was analysed after 4 d
of water deprivation and also 1 d after re-watering. The effects of ABA and of
methotrexate (MTX), an inhibitor of stomatal opening, on gene expression and
protein abundance were also analysed. Protein abundance was examined using
antibodies against PIP1 and PIP2 aquaporins. At the same time, root hydraulic
conductance (L), transpiration rate, leaf water status and ABA tissue
concentration were measured. KEY RESULTS: None of the treatments (drought, ABA or
MTX) changed the leaf water status or tissue ABA concentration. The three
treatments caused a decline in the transpiration rate and raised PVPIP2;1 gene
expression and PIP1 protein abundance in the leaves. In the roots, only the
drought treatment raised the expression of the three PIP genes examined, while at
the same time diminishing PIP2 protein abundance and L. On the other hand, ABA
raised both root PIP1 protein abundance and L. CONCLUSIONS: The rise of PvPIP2;1
gene expression and PIP1 protein abundance in the leaves of P. vulgaris plants
subjected to drought was correlated with a decline in the transpiration rate. At
the same time, the increase in the expression of the three PIP genes examined
caused by drought and the decline of PIP2 protein abundance in the root tissues
were not correlated with any of the parameters measured.
PMID- 17028298
TI - Seasonal timing of pseudoviviparous reproduction of Leiothrix (Eriocaulaceae)
rupestrian species in South-eastern Brazil.
AB - BACKGROUND AND AIMS: Pseudovivipary is an asexual reproductive strategy.
Leiothrix spiralis and L. vivipara (Eriocaulaceae) are pseudoviviparous and occur
in rupestrian grasslands, a habitat that has a predominance of sandy and shallow
soil, with low water retention. This study aims to investigate the seasonal
variation effect of moisture availability on L. spiralis and L. vivipara
pseudoviviparous reproduction, and to compare their life history attributes, on
rupestrian grasslands in Southeastern Brazil. METHODS: A field study was
conducted, including observations concerning pseudoviviparous reproduction and
measurement of demographic variables in both L. spiralis and L. vivipara. Soil
moisture measurements were also performed to study its effect on the
pseudoviviparous reproduction of L. spiralis and L. vivipara. KEY RESULTS: Flower
head and plantlet production in L. spiralis were highly correlated with soil
moisture. All scapes split off in the drier period, indicating that this is a
splitter ramet species. Plantlet mortality was positively correlated with scapes
splitting off. The L. vivipara phenophases were not synchronized to the variation
in soil moisture, since flower heads and plantlets were produced throughout the
year. Moreover, the splitting off of scapes was not observed. In addition,
plantlets were formed early, as soon as the flower heads appeared, and remained
suspended. Therefore, this species was called 'canopy forming'. CONCLUSIONS:
Seasonal timing of pseudoviviparous reproduction can be a vital component of the
successful establishment of plantlets in L. spiralis, considering that in this
species the plantlets are formed only after the flower head touches the ground.
In contrast, in L. vivipara, the plantlets are formed early, without touching the
ground. Moreover, L. spiralis is a splitter ramet species, while L. vivipara is a
canopy-forming species. The pseudoviviparous canopy-forming strategy appears to
be more advantageous than the splitter ramet strategy, because even under similar
soil moisture conditions, the survival of L. vivipara plantlets was greater than
that of L. spiralis.
PMID- 17028299
TI - Summer dormancy in perennial temperate grasses.
AB - BACKGROUND AND AIMS: Dormancy has been extensively studied in plants which
experience severe winter conditions but much less so in perennial herbaceous
plants that must survive summer drought. This paper reviews the current knowledge
on summer dormancy in both native and cultivated perennial temperate grasses
originating from the Mediterranean Basin, and presents a unified terminology to
describe this trait. SCOPE: Under severe drought, it is difficult to separate the
responses by which plants avoid and tolerate dehydration from those associated
with the expression of summer dormancy. Consequently, this type of endogenous
(endo-) dormancy can be tested only in plants that are not subjected to moisture
deficit. Summer dormancy can be defined by four criteria, one of which is
considered optional: (1) reduction or cessation of leaf production and expansion;
(2) senescence of mature foliage; (3) dehydration of surviving organs; and (4,
optional) formation of resting organs. The proposed terminology recognizes two
levels of summer dormancy: (a) complete dormancy, when cessation of growth is
associated with full senescence of foliage and induced dehydration of leaf bases;
and (b) incomplete dormancy, when leaf growth is partially inhibited and is
associated with moderate levels of foliage senescence. Summer dormancy is
expressed under increasing photoperiod and temperature. It is under hormonal
control and usually associated with flowering and a reduction in metabolic
activity in meristematic tissues. Dehydration tolerance and dormancy are
independent phenomena and differ from the adaptations of resurrection plants.
CONCLUSIONS: Summer dormancy has been correlated with superior survival after
severe and repeated summer drought in a large range of perennial grasses. In the
face of increasing aridity, this trait could be used in the development of
cultivars that are able to meet agronomic and environmental goals. It is
therefore important to have a better understanding of the genetic and
environmental control of summer dormancy.
PMID- 17028300
TI - Proteomic identification of macrophage migration-inhibitory factor upon exposure
to TiO2 particles.
AB - Inhalation of particulate matter aggravates respiratory symptoms in patients with
chronic airway diseases, but the mechanisms underlying this response remain
poorly understood. We used a proteomics approach to examine this phenomenon.
Treatment of epithelial cells with BSA-coated titanium dioxide (TiO(2)) particles
altered 20 protein spots on the two-dimensional gel, and these were then analyzed
by nano-LC-MS/MS. These proteins included defense-related, cell-activating, and
cytoskeletal proteins implicated in the response to oxidative stress. The
proteins were classified into four groups according to the time course of their
expression patterns. For validation, RT-PCR was performed on extracts of in vitro
TiO(2)-treated cells, and lung issues from TiO(2)-treated rats were analyzed by
immunohistochemical staining and enzyme immunoassay. TiO(2) treatment was found
to increase the amount of mRNA for macrophage migration-inhibitory factor (MIF).
MIF was expressed primarily in epithelium and was elevated in lung tissues and
bronchoalveolar lavage fluids of TiO(2)-treated rats as compared with sham
treated rats. Carbon black and diesel exhaust particles also induced expression
of MIF protein in the epithelial cells.
PMID- 17028301
TI - Morphine administration alters the profile of hippocampal postsynaptic density
associated proteins: a proteomics study focusing on endocytic proteins.
AB - Numerous studies have shown that drugs of abuse induce changes in protein
expression in the brain that are thought to play a role in synaptic plasticity.
Drug-induced plasticity can be mediated by changes at the synapse and more
specifically at the postsynaptic density (PSD), which receives and transduces
synaptic information. To date, the majority of studies examining synaptic protein
profiles have focused on identifying the synaptic proteome. Only a handful of
studies have examined the changes in synaptic profile by drug administration. We
applied a quantitative proteomics analysis technique with the cleavable ICAT
reagent to quantitate relative changes in protein levels of the hippocampal PSD
in response to morphine administration. We identified a total of 102 proteins in
the mouse hippocampal PSD. The majority of these were signaling, trafficking, and
cytoskeletal proteins involved in synaptic plasticity, learning, and memory.
Among the proteins whose levels were found to be altered by morphine
administration, clathrin levels were increased to the largest extent.
Immunoblotting and electron microscopy studies showed that this increase was
localized to the PSD. Morphine treatment was also found to lead to a local
increase in two other components of the endocytic machinery, dynamin and AP-2,
suggesting a critical involvement of the endocytic machinery in the modulatory
effects of morphine. Because alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid (AMPA) receptors are thought to undergo clathrin-mediated endocytosis, we
examined the effect of morphine administration on the association of the AMPA
receptor subunit, GluR1, with clathrin. We found a substantial decrease in the
levels of GluR1 associated with clathrin. Taken together, these results suggest
that, by causing a redistribution of endocytic proteins at the synapse, morphine
modulates synaptic plasticity at hippocampal glutamatergic synapses.
PMID- 17028302
TI - MicroRNAs in biological processes and carcinogenesis.
AB - MicroRNAs (miRNAs) encoding small non-coding RNAs have been recognized as a very
large gene family present in most organisms. The precise biological effects of
miRNAs are yet to be elucidated in detail, partly because each miRNA is believed
to negatively regulate the expression of hundreds of target genes. Nevertheless,
recent findings indicate that carcinogenic processes are associated with
alterations in the expression of several miRNAs, suggesting that some function as
oncogenes or tumor suppressor genes. The present review focuses on recent
findings in this exciting new area of research, with special emphasis on the
involvement of miRNAs in cancer development and progression. Further studies are
clearly warranted to elucidate the molecular and biological roles of miRNAs,
which may ultimately provide both a better understanding of disease development,
as well as a foundation for novel strategies for cancer diagnosis and therapy.
PMID- 17028303
TI - Association of DNA repair polymorphisms with DNA repair functional outcomes in
healthy human subjects.
AB - We investigated association between polymorphisms in DNA repair genes and the
capacity to repair DNA damage induced by gamma-irradiation and by base oxidation
in a healthy population. Irradiation-specific DNA repair rates were significantly
decreased in individuals with XRCC1 Arg399Gln homozygous variant genotype (0.45
+/- 0.47 SSB/10(9) Da) than in those with wild-type genotype (1.10 +/- 0.70
SSB/10(9) Da, P=0.0006, Mann-Witney U-test). The capacity to repair oxidative DNA
damage was significantly decreased among individuals with hOGG1 Ser326Cys
homozygous variant genotype (0.37 +/- 0.28 SSB/10(9) Da) compared to those with
wild-type genotype (0.83 +/- 0.79 SSB/10(9) Da, P=0.008, Mann-Witney U-test).
Investigation of genotype combinations showed that the increasing number of
variant alleles for both XRCC1 Arg399Gln and APE1 Asn148Glu polymorphisms
resulted in a significant decrease of irradiation-specific repair rates (P=0.008,
Kruskal-Wallis test). Irradiation-specific DNA repair rates also decreased with
increasing number of variant alleles in XRCC1 Arg399Gln in combination with
variant alleles for two other XRCC1 polymorphisms, Arg194Trp and Arg280His
(P=0.002 and P=0.005, respectively; Kruskal-Wallis test). In a binary combination
variant alleles of hOGG1 Ser326Cys and APE1 Asn148Glu polymorphisms were
associated with a significant decrease in the capacity to repair DNA oxidative
damage (P=0.018, Kruskal-Wallis test). In summary, XRCC1 Arg399Gln and hOGG1
Ser326Cys polymorphisms seem to exert the predominant modulating effect on
irradiation-specific DNA repair capacity and the capacity to repair DNA oxidative
damage, respectively.
PMID- 17028304
TI - Examining treatment use among alcohol-dependent individuals from a population
perspective.
AB - AIMS: To assess the prevalence of treatment use in lifetime and past year alcohol
dependent respondents. To establish the proportion of problem drinkers who use
alcohol treatment that just go to one treatment versus attending multiple
different types of treatment in the same year. To explore what treatments are
most likely to form part of a multiple treatment package. METHOD: Analysis of the
2001-2002 National Epidemiologic Survey of Alcohol and Related Conditions, a
large (N = 43 039), representative survey of the non-institutionalized adult
population of the USA. There were 4781 respondents who met criteria for a
lifetime definition of alcohol dependence and 1484 respondents who met criteria
for past year alcohol dependence. RESULTS: Prevalence of lifetime use of alcohol
treatment was 25% among those with a lifetime diagnosis of alcohol dependence.
Prevalence of past year use of alcohol treatment was 12% among respondents with
past year alcohol dependence. Only one-third of past year treatment users had
accessed just one type of alcohol treatment. CONCLUSIONS: While treatment
services are only used by the minority of people with alcohol dependence, those
people who do access alcohol treatment are likely to use several different
alcohol treatment services in the same year.
PMID- 17028305
TI - Drinking histories of self-identified lifetime abstainers and occasional
drinkers: findings from the 1958 British Birth Cohort Study.
AB - AIMS: To investigate the validity of retrospective items used to distinguish
people who have rarely or never consumed alcohol. METHODS: The 1958 British Birth
Cohort Study has followed 9377 individuals until age 45. Previous drinking (at
16, 23, 33 and 42 years) was investigated for two groups of 45-year-old non
drinkers, those reporting never having consumed alcohol ('never drinkers', n =
143, 1.5%), and having only consumed very infrequently ('occasional-only
drinkers', n = 1149, 12.3%). RESULTS: 67% of never drinkers previously reported
drinking, 25% were past weekly/daily drinkers; 56% of occasional-only drinkers
reported weekly/daily consumption. The validity of the retrospective items was
progressively questionable when presumed to cover longer time periods.
CONCLUSIONS: Substantial measurement error was evident when identifying
'occasional-only' and 'never' drinkers using retrospective items covering the
lifecourse. Researchers investigating potential health benefits associated with
moderate drinking need to incorporate more sophisticated methods when identifying
sub-groups of non-drinkers.
PMID- 17028306
TI - Lipid peroxidation and serum cytokines in acute alcoholic hepatitis.
AB - AIMS: Increased exposure of Kupffer cells to intestinal-borne Gram-negative
bacteria enhances the metabolism and leads to cytokine production by these cells.
Activation of Kupffer cells increases free radical release, which may, in turn,
enhance cytokine secretion, creating a positive feedback loop, which contributes
to liver inflammation. Cytokines act on T cells, inducing their proliferation and
secretion of additional interleukins. Lipid peroxidation products
(malondialdehyde; MDA) form adducts with proteins and acetaldehyde, triggering a
T cell immune response. Controversy exists about the predominance of either Th-1
or Th-2 cellular responses. We performed the present study in order to analyse
the cytokine pattern in patients with acute alcoholic hepatitis, its relation to
MDA and the relation between all these parameters and liver function and
prognosis. SUBJECTS AND METHODS: The study included 53 male alcoholics, 47
followed up for a median time of 32 months, during which 17 of them died. We
measured serum MDA, tumour necrosis factor-alpha, interferon gamma (IFNG) and
interleukins (IL) 4, 6, 8, and 10. RESULTS: MDA levels were raised in cirrhotics
and non-cirrhotics with alcoholic hepatitis, maintaining a relationship with
bilirubin and Maddrey index, and with mortality in the univariate analysis. Both
IFNG and IL-4 were raised in our patients compared with controls, as well as IL
8, and IL-6, but IL-10 were below the detection limit in the majority of cases,
especially in cirrhotics. Using a Cox regression model, Maddrey index displaced
MDA in the survival analysis. CONCLUSIONS: Our data lend support to the
hypothesis that activation of both Th-1 and Th-2 cell subsets take place. MDA
levels are raised in alcoholics with alcoholic hepatitis and are closely related
to liver function derangement and to survival, although this is displaced by
Maddrey index using Cox regression model.
PMID- 17028307
TI - The life and times of the J-shaped curve.
PMID- 17028308
TI - Assessing motivation for change in subjects with alcohol problems: the MAC2-A
questionnaire.
AB - AIMS: This article presents the validation study of a questionnaire (MAC2-A),
created to assess motivation for change in Italian adult subjects with alcohol
related problems who require or are referred for assessment and treatment. The
questionnaire evaluates readiness to change (RTC), self-efficacy and discrepancy.
METHODS: The questionnaire was validated on 419 subjects referred to 23 health
agencies in Italy. RESULTS: The questionnaire showed good internal consistency
and temporal stability. Exploratory and confirmatory factor analysis confirms the
consistency with the theoretical assumptions. Test-retest showed high reliability
on all scales except one. Visual analogue control scales used for reliability and
concurrent validity yielded strong correlations with the corresponding variables.
CONCLUSION: The study confirms the validity of the instrument, and its
consistency with the model. The MAC2-A questionnaire is the first psychometric
instrument integrating three factors (discrepancy, self-efficacy, RTC) into a 3D
model of motivation for change.
PMID- 17028309
TI - Differential enzymatic characteristics and tissue-specific expression of human
TPST-1 and TPST-2.
AB - Protein tyrosine sulfation is emerging as a widespread post-translational
modification in multicellular eukaryotes. The responsible enzyme, named
tyrosylprotein sulfotransferase (TPST), catalyzes the sulfate transfer from 3'
phosphoadenosine 5'-phosphosulfate to tyrosine residues of proteins. Two distinct
TPSTs, designated TPST-1 and TPST-2, had previously been identified. In the
present study, we cloned human TPST-1 and TPST-2 expressed and characterized the
recombinant enzymes using peptide substrates. These enzymes displayed distinct
acidic pH optima and stimulatory effects of Mn(2+). Additionally, the activity of
TPST-2, but not TPST-1, was stimulated in the presence of Mg(2+). Compared with
TPST-2, TPST-1 displayed considerably lower K(m) and V(max) for the majority of
the tested peptide substrates, implying their differential substrate specificity.
Quantitative real-time PCR analysis showed that although the two TPSTs were co
expressed in all 20 human tissues examined, the levels of expression of TPST-1
and TPST-2 varied significantly among different tissues. These latter findings
may imply distinct physiological functions of TPST-1 and TPST-2.
PMID- 17028310
TI - Language and memory disorder in the case of Jonathan Swift: considerations on
retrospective diagnosis.
AB - The cause of behavioural changes described by Alzheimer for his original case,
Auguste D., has been recently reconfirmed by histological examination. However,
there has been active speculation regarding the cause of behavioural changes
exhibited by the political satirist Jonathan Swift (1667-1745) during the final
three years of his life for over 250 years. Swift's symptoms of cognitive
changes, memory impairment, personality alterations, language disorder and facial
paralysis have all been apportioned differing levels of significance in various
attempts at retrospective diagnosis. The various medical arguments put forward
from the 18th through 20th centuries will be critically examined. The diagnoses
considered refer to evolving theories of insanity, phrenology, localization of
cortical function, hydrocephalus, psychoanalysis, aphasia, dementia and
depression in ageing. Re-consideration of the attempts to re-diagnose Swift's
final mental state by the leading neurological thinkers of the day, including
Wilde (The Closing Years of Dean Swift's Life. Dublin: Hodges and Smith, 1849),
Bucknill (1882), Osler [Osler's textbook Principles and Practice of Medicine
(1892); published in St Thomas's Hospital Gazette (London) 1902; 12: 59-60),
Brain (Irish Med J 1952: 320-1 and 337-346) and Boller and Forbes (J Neurol Sci
1998; 158: 125-133) reveal the changing attitudes regarding the significance of
behavioural symptoms to neurological diagnosis from the 18th century to the
present day.
PMID- 17028311
TI - Thiorphan, a neutral endopeptidase inhibitor used for diarrhoea, is
neuroprotective in newborn mice.
AB - Excitotoxic damage appears to be a critical factor in the formation of perinatal
brain lesions associated with cerebral palsy (CP). When injected into newborn
mice, the glutamatergic analogue, ibotenate, produces cortical lesions and white
matter cysts that mimic human perinatal brain lesions. Neuropeptides are neuronal
activity modulators and could therefore modulate glutamate-induced lesions.
However, neuropeptides are rapidly degraded by peptidases. Racecadotril, which is
rapidly metabolized to its active metabolite thiorphan, is a neutral
endopeptidase (NEP) inhibitor used in clinical practice for diarrhoea with a
remarkable safety profile. This study aimed to test the original hypothesis that
thiorphan could be neuroprotective against ibotenate-induced lesions in newborn
mice. Intraperitoneal administration of thiorphan reduced ibotenate-induced
cortical lesions by up to 57% and cortical caspase-3 cleavage by up to 59%. This
neuroprotective effect was long-lasting and was still observed when thiorphan was
administered 12 h after the insult, showing a remarkable window for therapeutic
intervention. Further supporting the neuroprotective effect of pharmacological
blockade of NEP, mouse pups with a genetic deletion of NEP displayed a
significantly reduced size of the ibotenate-induced cortical grey matter lesion
when compared with wild-type animals. Thiorphan effects were mimicked by
substance P (SP) and, in a less potent manner, by neurokinin A. Thiorphan effects
were inhibited by blockers of NK1 and NK2 receptors. Real-time reverse
transcription-polymerase chain reaction, autoradiography and immunohistochemistry
confirmed the expression of NK1 and NK2 receptors in the neonatal murine
neocortex. These data demonstrate that thiorphan prevents neonatal excitotoxic
cortical damage, an effect largely mediated by SP. Thiorphan could represent a
promising drug for the prevention of CP, which remains a challenging disease. In
a broader context, these results also raise potential implications for the
prevention of neurodegenerative diseases involving glutamate-mediated excitotoxic
neuronal death.
PMID- 17028312
TI - Correlation of mRNA expression and protein abundance affected by multiple
sequence features related to translational efficiency in Desulfovibrio vulgaris:
a quantitative analysis.
AB - The modest correlation between mRNA expression and protein abundance in large
scale data sets is explained in part by experimental challenges, such as
technological limitations, and in part by fundamental biological factors in the
transcription and translation processes. Among various factors affecting the mRNA
protein correlation, the roles of biological factors related to translation are
poorly understood. In this study, using experimental mRNA expression and protein
abundance data collected from Desulfovibrio vulgaris by DNA microarray and liquid
chromatography coupled with tandem mass spectrometry (LC-MS/MS) proteomic
analysis, we quantitatively examined the effects of several translational
efficiency-related sequence features on mRNA-protein correlation. Three classes
of sequence features were investigated according to different translational
stages: (i) initiation, Shine-Dalgarno sequences, start codon identity, and start
codon context; (ii) elongation, codon usage and amino acid usage; and (iii)
termination, stop codon identity and stop codon context. Surprisingly, although
it is widely accepted that translation initiation is the rate-limiting step for
translation, our results showed that the mRNA-protein correlation was affected
the most by the features at elongation stages, i.e., codon usage and amino acid
composition (5.3-15.7% and 5.8-11.9% of the total variation of mRNA-protein
correlation, respectively), followed by stop codon context and the Shine-Dalgarno
sequence (3.7-5.1% and 1.9-3.8%, respectively). Taken together, all sequence
features contributed to 15.2-26.2% of the total variation of mRNA-protein
correlation. This study provides the first comprehensive quantitative analysis of
the mRNA-protein correlation in bacterial D. vulgaris and adds new insights into
the relative importance of various sequence features in prokaryotic protein
translation.
PMID- 17028313
TI - De novo exon duplication in a new allele of mouse Glra1 (spasmodic).
AB - The novel neurological mutant Cincinatti arose by genomic duplication of exon 5
in the glycine receptor gene Glra1. The mutant transcript results in premature
protein truncation. A direct repeat of the pentamer GGGGC is present adjacent to
the breakpoints and may have mediated the duplication event by a replication
slippage mechanism.
PMID- 17028314
TI - An integrated in silico gene mapping strategy in inbred mice.
AB - In recent years in silico analysis of common laboratory mice has been introduced
and subsequently applied, in slightly different ways, as a methodology for gene
mapping. Previously we have demonstrated some limitation of the methodology due
to sporadic genetic correlations across the genome. Here, we revisit the three
main aspects that affect in silico analysis. First, we report on the use of
marker maps: we compared our existing 20,000 SNP map to the newly released
140,000 SNP map. Second, we investigated the effect of varying strain numbers on
power to map QTL. Third, we introduced a novel statistical approach: a cladistic
analysis, which is well suited for mouse genetics and has increased flexibility
over existing in silico approaches. We have found that in our examples of complex
traits, in silico analysis by itself does fail to uniquely identify quantitative
trait gene (QTG)-containing regions. However, when combined with additional
information, it may significantly help to prioritize candidate genes. We
therefore recommend using an integrated work flow that uses other genomic
information such as linkage regions, regions of shared ancestry, and gene
expression information to obtain a list of candidate genes from the genome.
PMID- 17028315
TI - roX RNAs are required for increased expression of X-linked genes in Drosophila
melanogaster males.
AB - The male-specific lethal (MSL) ribonucleoprotein complex is necessary for
equalization of X:A expression levels in Drosophila males, which have a single X
chromosome. It binds selectively to the male X chromosome and directs acetylation
of histone H4 at lysine 16 (H4Ac16), a modification linked to elevated
transcription. roX1 and roX2 noncoding RNAs are essential but redundant
components of this complex. Simultaneous removal of both roX RNAs reduces X
localization of the MSL proteins and permits their ectopic binding to autosomal
sites and the chromocenter. However, the MSL proteins still colocalize, and low
levels of H4Ac16 are detected at ectopic sites of MSL binding and residual sites
on the X chromosome of roX1- roX2- males. Microarray analysis was performed to
reveal the effect of roX1 and roX2 elimination on X-linked and autosomal gene
expression. Expression of the X chromosome is decreased by 26% in roX1- roX2-
male larvae. Enhanced expression could not be detected at autosomal sites of MSL
binding in roX1- roX2- males. These results implicate failure to compensate X
linked genes, rather than inappropriate upregulation of autosomal genes at
ectopic sites of MSL binding, as the primary cause of male lethality upon loss of
roX RNAs.
PMID- 17028316
TI - Cis-regulatory evolution of chalcone-synthase expression in the genus
Arabidopsis.
AB - The contribution of cis-regulation to adaptive evolutionary change is believed to
be essential, yet little is known about the evolutionary rules that govern
regulatory sequences. Here, we characterize the short-term evolutionary dynamics
of a cis-regulatory region within and among two closely related species, A.
lyrata and A. halleri, and compare our findings to A. thaliana. We focused on the
cis-regulatory region of chalcone synthase (CHS), a key enzyme involved in the
synthesis of plant secondary metabolites. We observed patterns of nucleotide
diversity that differ among species but do not depart from neutral expectations.
Using intra- and interspecific F1 progeny, we have evaluated functional cis
regulatory variation in response to light and herbivory, environmental cues,
which are known to induce CHS expression. We find that substantial cis-regulatory
variation segregates within and among populations as well as between species,
some of which results from interspecific genetic introgression. We further
demonstrate that, in A. thaliana, CHS cis-regulation in response to herbivory is
greater than in A. lyrata or A. halleri. Our work indicates that the evolutionary
dynamics of a cis-regulatory region is characterized by pervasive functional
variation, achieved mostly by modification of response modules to one but not all
environmental cues. Our study did not detect the footprint of selection on this
variation.
PMID- 17028317
TI - Contribution of growth and cell cycle checkpoints to radiation survival in
Drosophila.
AB - Cell cycle checkpoints contribute to survival after exposure to ionizing
radiation (IR) by arresting the cell cycle and permitting repair. As such, yeast
and mammalian cells lacking checkpoints are more sensitive to killing by IR. We
reported previously that Drosophila larvae mutant for grp (encoding a homolog of
Chk1) survive IR as well as wild type despite being deficient in cell cycle
checkpoints. This discrepancy could be due to differences either among species or
between unicellular and multicellular systems. Here, we provide evidence that
Grapes is needed for survival of Drosophila S2 cells after exposure to similar
doses of IR, suggesting that multicellular organisms may utilize checkpoint
independent mechanisms to survive irradiation. The dispensability of checkpoints
in multicellular organisms could be due to replacement of damaged cells by
regeneration through increased nutritional uptake and compensatory proliferation.
In support of this idea, we find that inhibition of nutritional uptake (by
starvation or onset of pupariation) or inhibition of growth factor signaling and
downstream targets (by mutations in cdk4, chico, or dmyc) reduced the radiation
survival of larvae. Further, some of these treatments are more detrimental for
grp mutants, suggesting that the need for compensatory proliferation is greater
for checkpoint mutants. The difference in survival of grp and wild-type larvae
allowed us to screen for small molecules that act as genotype-specific radiation
sensitizers in a multicellular context. A pilot screen of a small molecule
library from the National Cancer Institute yielded known and approved radio
sensitizing anticancer drugs. Since radiation is a common treatment option for
human cancers, we propose that Drosophila may be used as an in vivo screening
tool for genotype-specific drugs that enhance the effect of radiation therapy.
PMID- 17028319
TI - Double-strand break repair in bacteriophage T4: recombination effects of 3'-5'
exonuclease mutations.
AB - The role of 3'-5' exonucleases in double-strand break (DSB)-promoted
recombination was studied in crosses of bacteriophage T4, in which DSBs were
induced site specifically within the rIIB gene by SegC endonuclease in the DNA of
only one of the parents. Frequency of rII+ recombinants was measured in two
factor crosses of the type i x ets1, where ets1 designates an insertion in the
rIIB gene carrying the cleavage site for SegC and i's are rIIB or rIIA point
mutations located at various distances (12-2040 bp) from the ets1 site. The
frequency/distance relationship was obtained in crosses of the wild-type phage
and dexA1 (deficiency in deoxyribonuclease A), D219A (deficiency in the
proofreading exonuclease of DNA polymerase), and tsL42 (antimutator allele of DNA
polymerase) mutants. In all the mutants, recombinant frequency in crosses with
the i-markers located at 12 and 33 bp from ets1 was significantly enhanced,
implying better preservation of 3'-terminal sequences at the ends of the broken
DNA. The effects of dexA1 and D219A were additive, suggesting an independent
action of the corresponding nucleases in the DSB repair pathway. The
recombination enhancement in the dexA1 mutant was limited to short distances
(<100 bp from ets1), whereas in the D219A mutant a significant enhancement was
seen at all the tested distances. From the character of the frequency/distance
relationship, it is inferred that the synthesis-dependent strand-annealing
pathway may operate in the D219A mutant. The recombination-enhancing effect of
the tsL42 mutation could be explained by the hypothesis that the antimutator
43Exo removes a shorter stretch of paired nucleotides than the wild-type enzyme
does during hydrolysis of the unpaired terminus in the D-loop intermediate. The
role of the proofreading exonuclease in the formation of a robust replicative
fork is discussed.
PMID- 17028320
TI - Diverse roles for histone H2A modifications in DNA damage response pathways in
yeast.
AB - There are many types of DNA damage that are repaired by a multiplicity of
different repair pathways. All damage and repair occur in the context of
chromatin, and histone modifications are involved in many repair processes. We
have analyzed the roles of H2A and its modifications in repair by mutagenizing
modifiable residues in the N- and C-terminal tails of yeast H2A and by testing
strains containing these mutations in multiple DNA repair assays. We show that
residues in both tails are important for homologous recombination and
nonhomologous end-joining pathways of double-strand break repair, as well as for
survival of UV irradiation and oxidative damage. We show that H2A serine 122 is
important for repair and/or survival in each of these assays. We also observe a
complex pattern of H2A phosphorylation at residues S122, T126, and S129 in
response to different damage conditions. We find that overlapping but
nonidentical groups of H2A residues in both tails are involved in different
pathways of repair. These data suggest the presence of a set of H2A "damage
codes" in which distinct patterns of modifications on both tails of H2A may be
used to identify specific types of damage or to promote specific repair pathways.
PMID- 17028321
TI - Roles of PriA protein and double-strand DNA break repair functions in UV-induced
restriction alleviation in Escherichia coli.
AB - It has been widely considered that DNA modification protects the chromosome of
bacteria E. coli K-12 against their own restriction-modification systems.
Chromosomal DNA is protected from degradation by methylation of target sequences.
However, when unmethylated target sequences are generated in the host chromosome,
the endonuclease activity of the EcoKI restriction-modification enzyme is
inactivated by the ClpXP protease and DNA is protected. This process is known as
restriction alleviation (RA) and it can be induced by UV irradiation (UV-induced
RA). It has been proposed that chromosomal unmethylated target sequences, a
signal for the cell to protect its own DNA, can be generated by homologous
recombination during the repair of damaged DNA. In this study, we wanted to
further investigate the genetic requirements for recombination proteins involved
in the generation of unmethylated target sequences. For this purpose, we
monitored the alleviation of EcoKI restriction by measuring the survival of
unmodified lambda in UV-irradiated cells. Our genetic analysis showed that UV
induced RA is dependent on the excision repair protein UvrA, the RecA-loading
activity of the RecBCD enzyme, and the primosome assembly activity of the PriA
helicase and is partially dependent on RecFOR proteins. On the basis of our
results, we propose that unmethylated target sequences are generated at the D
loop by the strand exchange of two hemi-methylated duplex DNAs and subsequent
initiation of DNA replication.
PMID- 17028322
TI - emb-4 is a conserved gene required for efficient germline-specific chromatin
remodeling during Caenorhabditis elegans embryogenesis.
AB - In C. elegans, germline blastomeres are initially kept transcriptionally
quiescent by the maternally loaded CCCH zinc-finger protein PIE-1. PIE-1
disappears upon the birth of the primordial germ cells Z2 and Z3, yet these cells
appear to remain quiescent. We have previously demonstrated that there is a
chromatin-based repression that succeeds PIE-1 degradation. The chromatin in
Z2/Z3 loses certain histone modifications, including histone H3 lysine 4
dimethylation (H3K4me2), a conserved marker for transcriptionally competent
chromatin. We find that mutations in the maternal-effect gene emb-4 cause defects
in both PIE-1 degradation and germline-specific chromatin remodeling. emb-4
encodes a highly conserved protein with orthologs in fly, mouse, and human and
has a subtle role in Notch signaling. The embryonic phenotype of emb-4 is
consistent with a defect in the efficient and timely activation of developmental
programs, including germline chromatin remodeling. We also find that, as in early
somatic blastomeres, the degradation of PIE-1 in Z2/Z3 is facilitated by zinc
finger-interacting protein ZIF-1, and in the absence of either zif-1 or emb-4,
PIE-1 is abnormally retained in Z2/Z3.
PMID- 17028318
TI - Evolution of amino-acid sequences and codon usage on the Drosophila miranda neo
sex chromosomes.
AB - We have studied patterns of DNA sequence variation and evolution for 22 genes
located on the neo-X and neo-Y chromosomes of Drosophila miranda. As found
previously, nucleotide site diversity is greatly reduced on the neo-Y chromosome,
with a severely distorted frequency spectrum. There is also an accelerated rate
of amino-acid sequence evolution on the neo-Y chromosome. Comparisons of
nonsynonymous and silent variation and divergence suggest that amino-acid
sequences on the neo-X chromosome are subject to purifying selection, whereas
this is much weaker on the neo-Y. The same applies to synonymous variants
affecting codon usage. There is also an indication of a recent relaxation of
selection on synonymous mutations for genes on other chromosomes. Genes that are
weakly expressed on the neo-Y chromosome appear to have a faster rate of
accumulation of both nonsynonymous and unpreferred synonymous mutations than
genes with high levels of expression, although the rate of accumulation when both
types of mutation are pooled is higher for the neo-Y chromosome than for the neo
X chromosome even for highly expressed genes.
PMID- 17028323
TI - Duplication of centromeric histone H3 (HTR12) gene in Arabidopsis halleri and A.
lyrata, plant species with multiple centromeric satellite sequences.
AB - Arabidopsis halleri and lyrata have three different major centromeric satellite
sequences, a unique finding for a diploid Arabidopsis species. Since centromeric
histones coevolve with centromeric satellites, these proteins would be predicted
to show signs of selection when new centromere satellites have recently arisen.
We isolated centromeric protein genes from A. halleri and lyrata and found that
one of them, HTR12 (CENP-A), is duplicated, while CENP-C is not. Phylogenetic
analysis indicates that the HTR12 duplication occurred after these species
diverged from A. thaliana. Genetic mapping shows that HTR12 copy B has the same
genomic location as the A. thaliana gene; the other copy (A, at the other end of
the same chromosome) is probably the new copy. To test for selection since the
duplication, we surveyed diversity at both HTR12 loci within A. lyrata. Overall,
there is no strong evidence for an "evolutionary arms race" causing multiple
replacement substitutions. The A. lyrata HTR12B sequences fall into three classes
of haplotypes, apparently maintained for a long time, but they all encode the
same amino acid sequence. In contrast, HTR12A has low diversity, but many
variants are amino acid replacements, possibly due to independent selective
sweeps within populations of the species.
PMID- 17028325
TI - The maintenance of sex in bacteria is ensured by its potential to reload genes.
AB - Why sex is maintained in nature is a fundamental question in biology. Natural
genetic transformation (NGT) is a sexual process by which bacteria actively take
up exogenous DNA and use it to replace homologous chromosomal sequences. As it
has been demonstrated, the role of NGT in repairing deleterious mutations under
constant selection is insufficient for its survival, and the lack of other viable
explanations have left no alternative except that DNA uptake provides nucleotides
for food. Here we develop a novel simulation approach for the long-term dynamics
of genome organization (involving the loss and acquisition of genes) in a
bacterial species consisting of a large number of spatially distinct populations
subject to independently fluctuating ecological conditions. Our results show that
in the presence of weak interpopulation migration NGT is able to subsist as a
mechanism to reload locally lost, intermittently selected genes from the
collective gene pool of the species through DNA uptake from migrants. Reloading
genes and combining them with those in locally adapted genomes allow individual
cells to readapt faster to environmental changes. The machinery of transformation
survives under a wide range of model parameters readily encompassing real-world
biological conditions. These findings imply that the primary role of NGT is not
to serve the cell with food, but to provide homologous sequences for restoring
genes that have disappeared from or become degraded in the local population.
PMID- 17028324
TI - A point mutation in the Aspergillus nidulans sonBNup98 nuclear pore complex gene
causes conditional DNA damage sensitivity.
AB - The nuclear pore complex (NPC) is embedded in the nuclear envelope where it
mediates transport between the cytoplasm and nucleus and helps to organize
nuclear architecture. We previously isolated sonB1, a mutation encoding a single
amino acid substitution within the Aspergillus nidulans SONBnNup98 NPC protein
(nucleoporin). Here we demonstrate that this mutation causes marked DNA damage
sensitivity at 42 degrees . Although SONBnNup98 has roles in the G2 transition,
we demonstrate that the G2 DNA damage checkpoint is functional in the sonB1
mutant at 42 degrees . The MRN complex is composed of MRE11, RAD50, and NBS1 and
functions in checkpoint signaling, DNA repair, and telomere maintenance. At 42
degrees we find that the DNA damage response defect of sonB1 mutants causes
synthetic lethality when combined with mutations in scaANBS1, the A. nidulans
homolog of NBS1. We provide evidence that this synthetic lethality is independent
of MRN cell cycle checkpoint functions or MREAMRE11-mediated DNA repair
functions. We also demonstrate that the single A. nidulans histone H2A gene
contains the C-terminal SQE motif of histone H2AX isoforms and that this motif is
required for the DNA damage response. We propose that the sonB1 nucleoporin
mutation causes a defect in a novel part of the DNA damage response.
PMID- 17028326
TI - Effect of the major repeat sequence on mitotic recombination in Candida albicans.
AB - The major repeat sequence (MRS) is known to play a role in karyotypic variation
in Candida albicans. The MRS affects karyotypic variation by expanding and
contracting internal repeats, by altering the frequency of chromosome loss, and
by serving as a hotspot for chromosome translocation. We proposed that the
effects of the MRS on translocation could be better understood by examination of
the effect of the MRS on a similar event, mitotic recombination between two
chromosome homologs. We examined the frequency of mitotic recombination across an
MRS of average size (approximately 50 kb) as well as the rate of recombination in
a 325-kb stretch of DNA adjacent to the MRS. Our results indicate that mitotic
recombination frequencies across the MRS were not enhanced compared to the
frequencies measured across the 325-kb region adjacent to the MRS. Mitotic
recombination events were found to occur throughout the 325-kb region analyzed as
well as within the MRS itself. This analysis of mitotic recombination frequencies
across a large portion of chromosome 5 is the first large-scale analysis of
mitotic recombination done in C. albicans and indicates that mitotic
recombination frequencies are similar to the rates found in Saccharomyces
cerevisiae.
PMID- 17028328
TI - Functional characterization of Drosophila Translin and Trax.
AB - The vertebrate RNA and ssDNA-binding protein Translin has been suggested to
function in a variety of cellular processes, including DNA damage response, RNA
transport, and translational control. The Translin-associated factor X (Trax)
interacts with Translin, and Trax protein stability depends on the presence of
Translin. To determine the function of the Drosophila Translin and Trax, we
generated a translin null mutant and isolated a trax nonsense mutation. translin
and trax single and double mutants are viable, fertile, and phenotypically
normal. Meiotic recombination rates and chromosome segregation are also not
affected in translin and trax mutants. In addition, we found no evidence for an
increased sensitivity for DNA double-strand damage in embryos and developing
larvae. Together with the lack of evidence for their involvement in DNA double
strand break checkpoints, this argues against a critical role for Translin and
Trax in sensing or repairing such DNA damage. However, Drosophila translin is
essential for stabilizing the Translin interaction partner Trax, a function that
is surprisingly conserved throughout evolution. Conversely, trax is not essential
for Translin stability as trax mutants exhibit normal levels of Translin protein.
PMID- 17028327
TI - The histone deubiquitinating enzyme Ubp10 is involved in rDNA locus control in
Saccharomyces cerevisiae by affecting Sir2p association.
AB - Histone modifications influence chromatin structure and thus regulate the
accessibility of DNA to replication, recombination, repair, and transcription. We
show here that the histone deubiquitinating enzyme Ubp10 contributes to the
formation/maintenance of silenced chromatin at the rDNA by affecting Sir2p
association.
PMID- 17028329
TI - Molecular diversity after a range expansion in heterogeneous environments.
AB - Recent range expansions have probably occurred in many species, as they often
happen after speciation events, after ice ages, or after the introduction of
invasive species. While it has been shown that range expansions lead to patterns
of molecular diversity distinct from those of a pure demographic expansion, the
fact that many species do live in heterogeneous environments has not been taken
into account. We develop here a model of range expansion with a spatial
heterogeneity of the environment, which is modeled as a gamma distribution of the
carrying capacities of the demes. By allowing temporal variation of these
carrying capacities, our model becomes a new metapopulation model linking
ecological parameters to molecular diversity. We show by extensive simulations
that environmental heterogeneity induces a loss of genetic diversity within demes
and increases the degree of population differentiation. We find that
metapopulations with low average densities are much more affected by
environmental heterogeneity than metapopulations with high average densities,
which are relatively insensitive to spatial and temporal variations of the
environment. Spatial heterogeneity is shown to have a larger impact on genetic
diversity than temporal heterogeneity. Overall, temporal heterogeneity and local
extinctions are not found to leave any specific signature on molecular diversity
that cannot be produced by spatial heterogeneity.
PMID- 17028330
TI - Phylogenetic analysis of fungal centromere H3 proteins.
AB - Centromere H3 proteins (CenH3's) are variants of histone H3 specialized for
packaging centromere DNA. Unlike canonical H3, which is among the most conserved
of eukaryotic proteins, CenH3's are rapidly evolving, raising questions about
orthology and conservation of function across species. To gain insight on CenH3
evolution and function, a phylogenetic analysis was undertaken on CenH3 proteins
drawn from a single, ancient lineage, the Fungi. Using maximum-likelihood
methods, a credible phylogeny was derived for the conserved histone fold domain
(HFD) of 25 fungal CenH3's. The collection consisted mostly of hemiascomycetous
yeasts, but also included basidiomycetes, euascomycetes, and an archaeascomycete.
The HFD phylogeny closely recapitulated known evolutionary relationships between
the species, supporting CenH3 orthology. The fungal CenH3's lacked significant
homology in their N termini except for those of the Saccharomyces/Kluyveromyces
clade that all contained a region homologous to the essential N-terminal domain
found in Saccharomyces cerevisiae Cse4. The ability of several heterologous
CenH3's to function in S. cerevisiae was tested and found to correlate with
evolutionary distance. Domain swapping between S. cerevisiae Cse4 and the
noncomplementing Pichia angusta ortholog showed that species specificity could
not be explained by the presence or absence of any recognized secondary
structural element of the HFD.
PMID- 17028331
TI - Selection, recombination and demographic history in Drosophila miranda.
AB - Selection, recombination, and the demographic history of a species can all have
profound effects on genomewide patterns of variability. To assess the impact of
these forces in the genome of Drosophila miranda, we examine polymorphism and
divergence patterns at 62 loci scattered across the genome. In accordance with
recent findings in D. melanogaster, we find that noncoding DNA generally evolves
more slowly than synonymous sites, that the distribution of polymorphism
frequencies in noncoding DNA is significantly skewed toward rare variants
relative to synonymous sites, and that long introns evolve significantly slower
than short introns or synonymous sites. These observations suggest that most
noncoding DNA is functionally constrained and evolving under purifying selection.
However, in contrast to findings in the D. melanogaster species group, we find
little evidence of adaptive evolution acting on either coding or noncoding
sequences in D. miranda. Levels of linkage disequilibrium (LD) in D. miranda are
comparable to those observed in D. melanogaster, but vary considerably among
chromosomes. These patterns suggest a significantly lower rate of recombination
on autosomes, possibly due to the presence of polymorphic autosomal inversions
and/or differences in chromosome sizes. All chromosomes show significant
departures from the standard neutral model, including too much heterogeneity in
synonymous site polymorphism relative to divergence among loci and a general
excess of rare synonymous polymorphisms. These departures from neutral
equilibrium expectations are discussed in the context of nonequilibrium models of
demography and selection.
PMID- 17028332
TI - The transposable element landscape of the model legume Lotus japonicus.
AB - The largest component of plant and animal genomes characterized to date is
transposable elements (TEs). The availability of a significant amount of Lotus
japonicus genome sequence has permitted for the first time a comprehensive study
of the TE landscape in a legume species. Here we report the results of a combined
computer-assisted and experimental analysis of the TEs in the 32.4 Mb of finished
TAC clones. While computer-assisted analysis facilitated a determination of TE
abundance and diversity, the availability of complete TAC sequences permitted
identification of full-length TEs, which facilitated the design of tools for
genomewide experimental analysis. In addition to containing all TE types found in
previously characterized plant genomes, the TE component of L. japonicus
contained several surprises. First, it is the second species (after Oryza sativa)
found to be rich in Pack-MULEs, with >1000 elements that have captured and
amplified gene fragments. In addition, we have identified what appears to be a
legume-specific MULE family that was previously identified only in fungal
species. Finally, the L. japonicus genome contains many hundreds, perhaps
thousands of Sireviruses: Ty1/copia-like elements with an extra ORF.
Significantly, several of the L. japonicus Sireviruses have recently amplified
and may still be actively transposing.
PMID- 17028334
TI - The distribution of beneficial mutant effects under strong selection.
AB - For a general theory of adaptation, it is essential to know the distribution of
fitness effects of beneficial mutations. Recent theoretical and empirical studies
have made considerable progress in determining the characteristics of this
distribution. To date, the experiments have largely verified the theoretical
predictions. Despite the fact that the theoretical work has assumed small
selection coefficients, strong selection has been observed in some experiments,
especially those involving novel environments. Here, we derive the distribution
of fitness effects among fixed beneficial mutants without the restriction of low
selection coefficients. The fate of strongly favored alleles is less affected by
stochastic drift while rare, causing the distribution of fitness effects among
fixed beneficial mutations to reflect more closely the distribution among all
newly arising beneficial mutations. We also find that when many alleles compete
for fixation within an asexual population (clonal interference), the beneficial
effects of a newly fixed mutant cannot be well estimated because of the high
number of subsequent mutations that arise within the genome, regardless of
whether selection is strong or weak.
PMID- 17028333
TI - Testing chromosomal phylogenies and inversion breakpoint reuse in Drosophila.
AB - A combination of cytogenetic and bioinformatic procedures was used to test the
chromosomal phylogeny relating Drosophila buzzatii with D. repleta. Chromosomes X
and 2, harboring most of the inversions fixed between these two species, were
analyzed. First, chromosomal segments conserved during the divergence of the two
species were identified by comparative in situ hybridization to the D. repleta
chromosomes of 180 BAC clones from a BAC-based physical map of the D. buzzatii
genome. These conserved segments were precisely delimited with the aid of clones
containing inversion breakpoints. Then GRIMM software was used to estimate the
minimum number of rearrangements necessary to transform one genome into the other
and identify all possible rearrangement scenarios. Finally, the most plausible
inversion trajectory was tested by hybridizing 12 breakpoint-bearing BAC clones
to the chromosomes of seven other species in the repleta group. The results show
that chromosomes X and 2 of D. buzzatii and D. repleta differ by 12 paracentric
inversions. Nine of them are fixed in chromosome 2 and entail two breakpoint
reuses. Our results also show that the cytological relationship between D.
repleta and D. mercatorum is closer than that between D. repleta and D.
peninsularis, and we propose that the phylogenetic relationships in this lineage
of the repleta group be reconsidered. We also estimated the rate of rearrangement
between D. repleta and D. buzzatii and conclude that rates within the genus
Drosophila vary substantially between lineages, even within a single species
group.
PMID- 17028335
TI - On the generalized poisson regression mixture model for mapping quantitative
trait loci with count data.
AB - Statistical methods for mapping quantitative trait loci (QTL) have been
extensively studied. While most existing methods assume normal distribution of
the phenotype, the normality assumption could be easily violated when phenotypes
are measured in counts. One natural choice to deal with count traits is to apply
the classical Poisson regression model. However, conditional on covariates, the
Poisson assumption of mean-variance equality may not be valid when data are
potentially under- or overdispersed. In this article, we propose an interval
mapping approach for phenotypes measured in counts. We model the effects of QTL
through a generalized Poisson regression model and develop efficient likelihood
based inference procedures. This approach, implemented with the EM algorithm,
allows for a genomewide scan for the existence of QTL throughout the entire
genome. The performance of the proposed method is evaluated through extensive
simulation studies along with comparisons with existing approaches such as the
Poisson regression and the generalized estimating equation approach. An
application to a rice tiller number data set is given. Our approach provides a
standard procedure for mapping QTL involved in the genetic control of complex
traits measured in counts.
PMID- 17028336
TI - Substitution mapping in dahl rats identifies two distinct blood pressure
quantitative trait loci within 1.12- and 1.25-mb intervals on chromosome 3.
AB - Substitution mapping was used to refine the localization of blood pressure (BP)
quantitative trait loci (QTL) within the congenic region of S.R-Edn3 rats located
at the q terminus of rat chromosome 3 (RNO3). An F2(SxS.R-Edn3) population
(n=173) was screened to identify rats having crossovers within the congenic
region of RNO3 and six congenic substrains were developed that carry shorter
segments of R-rat-derived RNO3. Five of the six congenic substrains had
significantly lower BP compared to the parental S rat. The lack of BP lowering
effect demonstrated by the S.R(ET3x5) substrain and the BP lowering effect
retained by the S.R(ET3x2) substrain together define the RNO3 BP QTL-containing
region as approximately 4.64 Mb. Two nonoverlapping substrains, S.R(ET3x1) and
S.R(ET3x6), had significantly lower BP compared to the S strain, indicating the
presence of two distinct BP QTL in the RNO3 q terminus. The RNO3 q terminus was
fine mapped with newly developed polymorphic markers to characterize the extent
of the congenic regions. The two RNO3 BP QTL regions were thus defined as within
intervals of 0.05-1.12 and 0.72-1.25 Mb, respectively. Also important was our
difficulty in fine mapping and marker placement in this portion of the rat genome
(and thus candidate gene identification) using the available genomic data,
including the rat genome sequence.
PMID- 17028337
TI - Structure-function analysis of delta trafficking, receptor binding and signaling
in Drosophila.
AB - The transmembrane proteins Delta and Notch act as ligand and receptor in a
conserved signaling pathway required for a variety of cell fate specification
events in many organisms. Binding of Delta to Notch results in a proteolytic
cascade that releases the Notch intracellular domain, allowing it to participate
in transcriptional activation in the nucleus. Recent research has implicated the
endocytic and ubiquitylation machinery as essential components of Delta-Notch
signaling. Our analysis of chimeric and missense Delta variants has delineated a
number of structural requirements for Delta trafficking, receptor binding, and
signaling. We find that while the Delta N-terminal domain is necessary and
sufficient for binding to Notch, the integrity of the epidermal-growth-factor
like repeat (ELR) 2 is also required for Notch binding. Screening of 117 Delta
mutant lines for proteins that exhibit aberrant subcellular trafficking has led
to the identification of 18 Delta alleles (DlTD alleles) that encode "trafficking
defective" Delta proteins. We find, unexpectedly, that many DlTD alleles contain
missense mutations in ELRs within the Delta extracellular domain. Finally, we
find that two DlTD alleles contain lysine missense mutations within the Delta
intracellular domain (DeltaICD) that may identify residues important for DeltaICD
mono-ubiquitylation and subsequent Delta endocytosis and signaling.
PMID- 17028338
TI - The association among gene expression responses to nine abiotic stress treatments
in Arabidopsis thaliana.
AB - The identification and analysis of genes exhibiting large expression responses to
several different types of stress may provide insights into the functional basis
of multiple stress tolerance in plant species. This study considered whole-genome
transcriptional profiles from Arabidopsis thaliana root and shoot organs under
nine abiotic stress conditions (cold, osmotic stress, salt, drought, genotoxic
stress, ultraviolet light, oxidative stress, wounding, and high temperature) and
at six different time points of stress exposure (0.5, 1, 3, 6, 12, and 24 hr). In
roots, genomewide correlations between transcriptional responses to different
stress treatments peaked following 1 hr of stress exposure, while in shoots,
correlations tended to increase following 6 hr of stress exposure. The generality
of stress responses at the transcriptional level was therefore time and organ
dependent. A total of 67 genes were identified as exhibiting a statistically
significant pattern of gene expression characterized by large transcriptional
responses to all nine stress treatments. Most genes were identified from early to
middle (1-6 hr) time points of stress exposure. Analysis of this gene set
indicated that cell rescue/defense/virulence, energy, and metabolism functional
classes were overrepresented, providing novel insight into the functional basis
of multiple stress tolerance in Arabidopsis.
PMID- 17028339
TI - Association mapping of complex trait loci with context-dependent effects and
unknown context variable.
AB - A novel method for Bayesian analysis of genetic heterogeneity and multilocus
association in random population samples is presented. The method is valid for
quantitative and binary traits as well as for multiallelic markers. In the
method, individuals are stochastically assigned into two etiological groups that
can have both their own, and possibly different, subsets of trait-associated
(disease-predisposing) loci or alleles. The method is favorable especially in
situations when etiological models are stratified by the factors that are unknown
or went unmeasured, that is, if genetic heterogeneity is due to, for example,
unknown genes x environment or genes x gene interactions. Additionally, a
heterogeneity structure for the phenotype does not need to follow the structure
of the general population; it can have a distinct selection history. The
performance of the method is illustrated with simulated example of genes x
environment interaction (quantitative trait with loosely linked markers) and
compared to the results of single-group analysis in the presence of missing data.
Additionally, example analyses with previously analyzed cystic fibrosis and type
2 diabetes data sets (binary traits with closely linked markers) are presented.
The implementation (written in WinBUGS) is freely available for research purposes
from http://www.rni.helsinki.fi/ approximately mjs/.
PMID- 17028340
TI - The X chromosome in quantitative trait locus mapping.
AB - The X chromosome requires special treatment in the mapping of quantitative trait
loci (QTL). However, most QTL mapping methods, and most computer programs for QTL
mapping, have focused exclusively on autosomal loci. We describe a method for
appropriate treatment of the X chromosome for QTL mapping in experimental
crosses. We address the important issue of formulating the null hypothesis of no
linkage appropriately. If the X chromosome is treated like an autosome, a sex
difference in the phenotype can lead to spurious linkage on the X chromosome.
Further, the number of degrees of freedom for the linkage test may be different
for the X chromosome than for autosomes, and so an X chromosome-specific
significance threshold is required. To address this issue, we propose a general
procedure to obtain chromosome-specific significance thresholds that controls the
genomewide false positive rate at the desired level. We apply our methods to data
on gut length in a large intercross of mice carrying the Sox10Dom mutation, a
model of Hirschsprung disease. We identified QTL contributing to variation in gut
length on chromosomes 5 and 18. We found suggestive evidence of linkage to the X
chromosome, which would be viewed as strong evidence of linkage if the X
chromosome was treated as an autosome. Our methods have been implemented in the
package R/qtl.
PMID- 17028341
TI - An Arabidopsis basic helix-loop-helix leucine zipper protein modulates metal
homeostasis and auxin conjugate responsiveness.
AB - The plant hormone auxin can be regulated by formation and hydrolysis of amide
linked indole-3-acetic acid (IAA) conjugates. Here, we report the
characterization of the dominant Arabidopsis iaa-leucine resistant3 (ilr3-1)
mutant, which has reduced sensitivity to IAA-Leu and IAA-Phe, while retaining
wild-type responses to free IAA. The gene defective in ilr3-1 encodes a basic
helix-loop-helix leucine zipper protein, bHLH105, and the ilr3-1 lesion results
in a truncated product. Overexpressing ilr3-1 in wild-type plants recapitulates
certain ilr3-1 mutant phenotypes. In contrast, the loss-of-function ilr3-2 allele
has increased IAA-Leu sensitivity compared to wild type, indicating that the ilr3
1 allele confers a gain of function. Microarray and quantitative real-time PCR
analyses revealed five downregulated genes in ilr3-1, including three encoding
putative membrane proteins similar to the yeast iron and manganese transporter
Ccc1p. Transcript changes are accompanied by reciprocally misregulated metal
accumulation in ilr3-1 and ilr3-2 mutants. Further, ilr3-1 seedlings are less
sensitive than wild type to manganese, and auxin conjugate response phenotypes
are dependent on exogenous metal concentration in ilr3 mutants. These data
suggest a model in which the ILR3/bHLH105 transcription factor regulates
expression of metal transporter genes, perhaps indirectly modulating IAA
conjugate hydrolysis by controlling the availability of metals previously shown
to influence IAA-amino acid hydrolase protein activity.
PMID- 17028343
TI - Dynamic genetic interactions determine odor-guided behavior in Drosophila
melanogaster.
AB - Understanding the genetic architecture of complex traits requires identification
of the underlying genes and characterization of gene-by-gene and genotype-by
environment interactions. Behaviors that mediate interactions between organisms
and their environment are complex traits expected to be especially sensitive to
environmental conditions. Previous studies on the olfactory avoidance response of
Drosophila melanogaster showed that the genetic architecture of this model
behavior depends on epistatic networks of pleiotropic genes. We performed a
screen of 1339 co-isogenic p[GT1]-element insertion lines to identify novel genes
that contribute to odor-guided behavior and identified 55 candidate genes with
known p[GT1]-element insertion sites. Characterization of the expression profiles
of 10 p[GT1]-element insertion lines showed that the effects of the transposon
insertions are often dependent on developmental stage and that hypomorphic
mutations in developmental genes can elicit profound adult behavioral deficits.
We assessed epistasis among these genes by constructing all possible double
heterozygotes and measuring avoidance responses under two stimulus conditions. We
observed enhancer and suppressor effects among subsets of these P-element-tagged
genes, and surprisingly, epistatic interactions shifted with changes in the
concentration of the olfactory stimulus. Our results show that the manifestation
of epistatic networks dynamically changes with alterations in the environment.
PMID- 17028342
TI - Types and rates of sequence evolution at the high-molecular-weight glutenin locus
in hexaploid wheat and its ancestral genomes.
AB - The Glu-1 locus, encoding the high-molecular-weight glutenin protein subunits,
controls bread-making quality in hexaploid wheat (Triticum aestivum) and
represents a recently evolved region unique to Triticeae genomes. To understand
the molecular evolution of this locus region, three orthologous Glu-1 regions
from the three subgenomes of a single hexaploid wheat species were sequenced,
totaling 729 kb of sequence. Comparing each Glu-1 region with its corresponding
homologous region from the D genome of diploid wheat, Aegilops tauschii, and the
A and B genomes of tetraploid wheat, Triticum turgidum, revealed that, in
addition to the conservation of microsynteny in the genic regions, sequences in
the intergenic regions, composed of blocks of nested retroelements, are also
generally conserved, although a few nonshared retroelements that differentiate
the homologous Glu-1 regions were detected in each pair of the A and D genomes.
Analysis of the indel frequency and the rate of nucleotide substitution, which
represent the most frequent types of sequence changes in the Glu-1 regions,
demonstrated that the two A genomes are significantly more divergent than the two
B genomes, further supporting the hypothesis that hexaploid wheat may have more
than one tetraploid ancestor.
PMID- 17028344
TI - The Cdc34/SCF ubiquitination complex mediates Saccharomyces cerevisiae cell wall
integrity.
AB - To identify novel functions for the Cdc34/SCF ubiquitination complex, we analyzed
genomewide transcriptional profiles of cdc53-1 and cdc34-2 Saccharomyces
cerevisiae mutants. This analysis revealed altered expression for several gene
families, including genes involved in the regulation of cell wall organization
and biosynthesis. This led us to uncover a role for the Cdc34/SCF complex in the
regulation of cell wall integrity. In support of this, cdc53-1 and cdc34-2
mutants exhibit phenotypes characteristic of cell wall integrity mutants, such as
SDS sensitivity and temperature-sensitive suppression by osmotic stabilizers.
Examination of these mutants revealed defects in their induction of Slt2
phosphorylation, indicating defects in Pkc1-Slt2 MAPK signaling. Consistent with
this, synthetic genetic interactions were observed between the genes encoding the
Cdc34/SCF complex and key components of the Pck1-Slt2 MAPK pathway. Further
analysis revealed that Cdc34/SCF mutants have reduced levels of active Rho1,
suggesting that these defects stem from the deregulated activity of the Rho1
GTPase. Altering the activity of Rho1 via manipulation of the Rho1-GAPs LRG1 or
SAC7 affected Cdc34/SCF mutant growth. Strikingly, however, deletion of LRG1
rescued the growth defects associated with Cdc34/SCF mutants, whereas deletion of
SAC7 enhanced these defects. Given the differential roles that these GAPs play in
the regulation of Rho1, these observations indicate the importance of
coordinating Cdc34/SCF activity with specific Rho1 functions.
PMID- 17028345
TI - Centromere-proximal crossovers are associated with precocious separation of
sister chromatids during meiosis in Saccharomyces cerevisiae.
AB - In most organisms, meiotic chromosome segregation is dependent on crossovers
(COs), which enable pairs of homologous chromosomes to segregate to opposite
poles at meiosis I. In mammals, the majority of meiotic chromosome segregation
errors result from a lack of COs between homologs. Observations in Homo sapiens
and Drosophila melanogaster have revealed a second class of exceptional events in
which a CO occurred near the centromere of the missegregated chromosome. We show
that in wild-type strains of Saccharomyces cerevisiae, most spore inviability is
due to precocious separation of sister chromatids (PSSC) and that PSSC is often
associated with centromere-proximal crossing over. COs, as opposed to
nonreciprocal recombination events (NCOs), are preferentially associated with
missegregation. Strains mutant for the RecQ homolog, SGS1, display reduced spore
viability and increased crossing over. Much of the spore inviability in sgs1
results from PSSC, and these events are often associated with centromere-proximal
COs, just as in wild type. When crossing over in sgs1 is reduced by the
introduction of a nonnull allele of SPO11, spore viability is improved,
suggesting that the increased PSSC is due to increased crossing over. We present
a model for PSSC in which a centromere-proximal CO promotes local loss of sister
chromatid cohesion.
PMID- 17028346
TI - Statistical epistasis is a generic feature of gene regulatory networks.
AB - Functional dependencies between genes are a defining characteristic of gene
networks underlying quantitative traits. However, recent studies show that the
proportion of the genetic variation that can be attributed to statistical
epistasis varies from almost zero to very high. It is thus of fundamental as well
as instrumental importance to better understand whether different functional
dependency patterns among polymorphic genes give rise to distinct statistical
interaction patterns or not. Here we address this issue by combining a
quantitative genetic model approach with genotype-phenotype models capable of
translating allelic variation and regulatory principles into phenotypic variation
at the level of gene expression. We show that gene regulatory networks with and
without feedback motifs can exhibit a wide range of possible statistical genetic
architectures with regard to both type of effect explaining phenotypic variance
and number of apparent loci underlying the observed phenotypic effect. Although
all motifs are capable of harboring significant interactions, positive feedback
gives rise to higher amounts and more types of statistical epistasis. The results
also suggest that the inclusion of statistical interaction terms in genetic
models will increase the chance to detect additional QTL as well as functional
dependencies between genetic loci over a broad range of regulatory regimes. This
article illustrates how statistical genetic methods can fruitfully be combined
with nonlinear systems dynamics to elucidate biological issues beyond reach of
each methodology in isolation.
PMID- 17028347
TI - Molecular analysis, cytogenetics and fertility of introgression lines from
transgenic wheat to Aegilops cylindrica host.
AB - Natural hybridization and backcrossing between Aegilops cylindrica and Triticum
aestivum can lead to introgression of wheat DNA into the wild species. Hybrids
between Ae. cylindrica and wheat lines bearing herbicide resistance (bar),
reporter (gus), fungal disease resistance (kp4), and increased insect tolerance
(gna) transgenes were produced by pollination of emasculated Ae. cylindrica
plants. F1 hybrids were backcrossed to Ae. cylindrica under open-pollination
conditions, and first backcrosses were selfed using pollen bags. Female fertility
of F1 ranged from 0.03 to 0.6%. Eighteen percent of the sown BC1s germinated and
flowered. Chromosome numbers ranged from 30 to 84 and several of the plants bore
wheat-specific sequence-characterized amplified regions (SCARs) and the bar gene.
Self fertility in two BC1 plants was 0.16 and 5.21%, and the others were
completely self-sterile. Among 19 BC1S1 individuals one plant was transgenic, had
43 chromosomes, contained the bar gene, and survived glufosinate treatments. The
other BC1S1 plants had between 28 and 31 chromosomes, and several of them carried
SCARs specific to wheat A and D genomes. Fertility of these plants was higher
under open-pollination conditions than by selfing and did not necessarily
correlate with even or euploid chromosome number. Some individuals having
supernumerary wheat chromosomes recovered full fertility.
PMID- 17028348
TI - Functional analysis of genes differentially expressed in the Drosophila wing
disc: role of transcripts enriched in the wing region.
AB - Differential gene expression is the major mechanism underlying the development of
specific body regions. Here we assessed the role of genes differentially
expressed in the Drosophila wing imaginal disc, which gives rise to two distinct
adult structures: the body wall and the wing. Reverse genetics was used to test
the function of uncharacterized genes first identified in a microarray screen as
having high levels of expression in the presumptive wing. Such genes could
participate in elaborating the specific morphological characteristics of the
wing. The activity of the genes was modulated using misexpression and RNAi
mediated silencing. Misexpression of eight of nine genes tested caused
phenotypes. Of 12 genes tested, 10 showed effective silencing with RNAi
transgenes, but only 3 of these had resulting phenotypes. The wing phenotypes
resulting from RNAi suggest that CG8780 is involved in patterning the veins in
the proximal region of the wing blade and that CG17278 and CG30069 are required
for adhesion of wing surfaces. Venation and apposition of the wing surfaces are
processes specific to wing development providing a correlation between the
expression and function of these genes. The results show that a combination of
expression profiling and tissue-specific gene silencing has the potential to
identify new genes involved in wing development and hence to contribute to our
understanding of this process. However, there are both technical and biological
limitations to this approach, including the efficacy of RNAi and the role that
gene redundancy may play in masking phenotypes.
PMID- 17028350
TI - Prevention of medication error and unintentional drug poisoning in the elderly.
PMID- 17028349
TI - Reduced dosage of pos-1 suppresses Mex mutants and reveals complex interactions
among CCCH zinc-finger proteins during Caenorhabditis elegans embryogenesis.
AB - Cell fate specification in the early C. elegans embryo requires the activity of a
family of proteins with CCCH zinc-finger motifs. Two members of the family, MEX-5
and MEX-6, are enriched in the anterior of the early embryo where they inhibit
the accumulation of posterior proteins. Embryos from mex-5 single-mutant mothers
are inviable due to the misexpression of SKN-1, a transcription factor that can
specify mesoderm and endoderm. The aberrant expression of SKN-1 causes a loss of
hypodermal and neuronal tissue and an excess of pharyngeal muscle, a Mex
phenotype (muscle excess). POS-1, a third protein with CCCH motifs, is
concentrated in the posterior of the embryo where it restricts the expression of
at least one protein to the anterior. We discovered that reducing the dosage of
pos-1(+) can suppress the Mex phenotype of mex-5(-) embryos and that POS-1 binds
the 3'-UTR of mex-6. We propose that the suppression of the Mex phenotype by
reducing pos-1(+) is due to decreased repression of mex-6 translation. Our
detailed analyses of these protein functions reveal complex interactions among
the CCCH finger proteins and suggest that their complementary expression patterns
might be refined by antagonistic interactions among them.
PMID- 17028351
TI - Drug-induced hypoglycaemia--new insight into an old problem.
AB - OBJECTIVE: To review the causes of drug-induced hypoglycaemia in patients not
taking hypoglycaemic medications. DESIGN: Retrospective study. SETTING: Regional
hospitals in Hong Kong. PATIENTS: Patients with suspected drug-induced
hypoglycaemia without a known history of exposure to hypoglycaemic agents,
referred to the Hospital Authority Toxicology Reference Laboratory from June 2005
to March 2006 inclusive. MAIN OUTCOME MEASURES: Rate of positive cases,
laboratory findings, possible causes, age distribution, and final outcomes.
RESULTS: A total of 51 such patients were referred, in whom the presence of oral
hypoglycaemic agents was detected (or inferred) in 23 (45%). In 12 of the 23
patients, oral hypoglycaemic agents could only be detected by target analysis,
not through broad-spectrum screening. Gliclazide and glibenclamide were detected
in 14 and eight patients respectively, whereas glimepiride, nateglinide and
rosiglitazone were detected in the remaining patient. Possible sources of oral
hypoglycaemic agents included drug administration errors in residential care
homes for the elderly (n=9), mistakenly taking medication of a family member or
employer (n=6), taking stock medication by mistake (n=2), taking Chinese
proprietary medicine adulterated with oral hypoglycaemic agents (n=1), taking
unknown pills bought from a retail pharmacy (n=1), and unknown (n=4). Regarding
these 23 patients, 17 (74%) were aged 70 years or above and 21 (91%) recovered
uneventfully. CONCLUSION: Hypoglycaemia due to inadvertent use of oral
hypoglycaemic agents is a recognised problem, particularly in cases where family
members living in the same household are taking similar medications. Possible
drug administration errors in residential care homes for the elderly should be
investigated, and procedures rectified if confirmed. Health care providers should
be vigilant to such potential errors, especially in cases of unexplained
hypoglycaemia.
PMID- 17028352
TI - Twelve years' local experience in ambulatory anaesthesia.
AB - OBJECTIVES: To determine the incidence of adverse events after ambulatory
anaesthesia (postoperative nausea and vomiting, postoperative pain, difficulty in
movement), and to evaluate the level of satisfaction of patients with our
service. DESIGN: Retrospective study with questionnaire survey. SETTING: Tertiary
referral centre, Hong Kong. PARTICIPANTS: All patients whose duly completed
questionnaires were available. MAIN OUTCOME MEASURES: Incidence of adverse events
and level of patient satisfaction. RESULTS: A total of 9197 patients underwent
surgery under general anaesthesia or neuraxial blockade by anaesthetists in
ambulatory settings from October 1993 to December 2005: questionnaires filled out
by 8231 of these patients were analysed, whereas 549 questionnaires were lost,
and 417 patients could not be contacted. The response rate was 90%; 59% of the
respondents were males, 50% were younger than 15 years and 5% older than 60
years. Fifty-one percent of surgery with anaesthetists' involvement was performed
under general anaesthesia and 48.9% under general anaesthesia and regional blocks
and 0.1% under neuraxial blockade. There were 3.3% of patients experienced
postoperative nausea and vomiting, 60.2% experienced episodes of pain between the
time of discharge and the time of interview, and 46% required analgesics.
Nonetheless, 80% resumed normal activities within 5 hours after anaesthesia and
97.5% resumed normal diet the following morning. Over 99% rated our service as
good or excellent. CONCLUSION: Although ambulatory anaesthesia was associated
with minor adverse events, patients could resume normal diet and daily activities
quickly and were satisfied with the service.
PMID- 17028353
TI - Sublingual misoprostol compared to artificial rupture of membranes plus oxytocin
infusion for labour induction in nulliparous women with a favourable cervix at
term.
AB - OBJECTIVES: To compare the efficacy of labour induction using sublingual
misoprostol versus combined artificial rupture of membranes and oxytocin infusion
for nulliparous women with a favourable cervix at term. DESIGN: Open randomised
controlled trial. SETTING: Regional hospital, Hong Kong. PATIENTS: Fifty
nulliparous women with a favourable cervix (Bishop score 6 or more) at term and
indications for labour induction. INTERVENTIONS: With their informed consent, 100
eligible women were to be randomised to receive either sublingual misoprostol 50
micrograms every 4 hours for up to five doses or oxytocin infusion after
artificial rupture of membranes. Interim analysis was planned at a sample size of
50. MAIN OUTCOME MEASURES: Vaginal delivery within 24 hours of induction.
RESULTS: The study was terminated when interim analysis of the first 50 recruits
showed that a significantly smaller proportion of misoprostol-treated women
delivered vaginally within 24 hours of induction than in the conventional
treatment group (68% vs 100%; relative risk, 0.68; 95% confidence interval, 0.51
0.91; P=0.009), although comparable numbers of women eventually delivered
vaginally. The mean induction to vaginal delivery interval was 4.5 hours longer
in the misoprostol group (P=0.027). After misoprostol treatment, all women went
into labour. Forty percent of them delivered without oxytocin. There was no
significant difference in uterine hyperstimulation rate, operative delivery rate,
and neonatal outcomes. Maternal satisfaction was higher in the misoprostol group
(92% vs 60%; relative risk, 1.53; 95% confidence interval, 1.09-2.16; P=0.008).
CONCLUSIONS: Despite being well accepted by women, labour induction using this
regimen of sublingual misoprostol is less effective in achieving vaginal delivery
within 24 hours.
PMID- 17028354
TI - Hong Kong men with low incomes have worse health-related quality of life as
judged by SF-36 scores.
AB - OBJECTIVE: To analyse the association between income and health-related quality
of life using the Medical Outcome Study Short Form 36 (SF-36) Chinese version in
Hong Kong Chinese working population. DESIGN: Cross-sectional observation study.
SETTING: A commercial company in Hong Kong. PARTICIPANTS: All clerical and
administrative staff of a commercial company was invited to participate; 876 of
the 1003 staff agreed. The subjects were categorised into three income groups
according to monthly income in Hong Kong dollars (low, < or =10,000; middle,
>10,000-25,000; high, >25,000). The mean age of the 288 men and 588 women was
34.9 (standard deviation, 7.9; median, 34.0; range, 18-71) years. MAIN OUTCOME
MEASURES: SF-36 scores on health-related quality of life. RESULTS: The
distribution of income was 30% in high-, 54.8% in middle-, and 15.2% in low
income groups. Women had similar SF-36 scores among different income groups. In
men, for most variables there was a significant positive linear correlation
between income and SF-36 scores. CONCLUSION: Low income is associated with a
worse health-related quality of life in Hong Kong Chinese men.
PMID- 17028355
TI - The short-to-midterm results of endovascular stent grafting for acute thoracic
aortic diseases in Chinese patients.
AB - OBJECTIVE: To review the results of endovascular treatment of acute thoracic
aortic diseases in a group of Chinese patients. DESIGN: Retrospective study.
SETTING: A tertiary referral hospital with a cardiothoracic surgery service.
PATIENTS: All 15 patients presenting with acute thoracic aortic diseases between
September 2001 and October 2005 inclusive, of whom eight had traumatic rupture,
four had complicated acute dissections, two had mycotic aneurysms, and one an
aneurysm with an aortobronchial fistula. INTERVENTIONS: Thoracic aortic stent
grafting. MAIN OUTCOME MEASURES: Immediate success, 6-month and 1-year survival
rates. RESULTS: The median follow-up period was 20.6 months (range, 0-50.1
months). Stent grafts were deployed with immediate success in all patients. Two
patients had ancillary bypass surgery for the supra-aortic branches. There were
two in-hospital deaths. Four sustained access artery injury and needed graft
repair. Computed tomography at 1 month showed complete thrombosis of the
aneurysmal lumen or the thoracic aortic false lumen in 12 of 13 survivors.
Computed tomography at 6 months showed complete thrombosis of the aneurysmal
lumen or the false lumen in nine of 10 patients due for follow-up. Both 6-month
and 1-year survival rates were 87%. CONCLUSIONS: Thoracic aortic stent grafting
for acute thoracic aortic disease is feasible and has a high success rate, with
good short-to-midterm results. However, the large size of the stent graft
introducer set imposes a high risk of access artery injury, for which further
improvements are necessary.
PMID- 17028356
TI - Uterine fibroid embolisation in Chinese women: medium-term results.
AB - OBJECTIVE: To evaluate the medium-term results of uterine fibroid embolisation in
Chinese women with symptomatic uterine fibroids. DESIGN: Prospective case series
study. SETTING: Gynaecology and Interventional Radiology units in a public
hospital, Hong Kong. PATIENTS: Patients with symptomatic fibroids who underwent
uterine fibroid embolisation in Queen Elizabeth Hospital from October 1998 to
June 2004. RESULTS: Fifty women (mean age, 42.9 years; median follow-up period,
27.5 months) were recruited. Most (82%) had menorrhagia as the chief presenting
symptom. Embolisation was successful in 49 (98%) women. Complications occurred in
12 (24%) patients, but were all self-limiting. Significant decrease in the median
clinical uterine size (14 weeks vs 10 weeks) and median volume of the largest
fibroid on magnetic resonance imaging (157.9 mL vs 45 mL) were observed during
the first year. The reduction seemed to be maintained till the last follow-up.
Menorrhagia improved in 34 (84%) patients, dysmenorrhoea in 28 (88%), pelvic pain
in 18 (82%) and abdominal mass in 15 (83%). Poor response was found for urinary
symptoms (29% improvement). Eight (16%) patients underwent hysterectomies after
uterine fibroid embolisation. On logistic regression analysis, the only
significant predictive factor for symptomatic improvement was fibroid volume
reduction at 6 months (P=0.03). CONCLUSION: Uterine fibroid embolisation is an
effective uterine-preserving therapy in patients with symptomatic fibroids;
overall symptomatic improvement was estimated as 80%. Uterine or fibroid size
reduction correlated well with clinical outcome. The impact of uterine fibroid
embolisation on young women wishing to conceive is yet to be determined.
PMID- 17028357
TI - Immuno-prophylaxis of babies borne to hepatitis B carrier mothers.
AB - OBJECTIVES: To examine the efficacy of current hepatitis B immuno-prophylaxis and
estimate the prevalence of S-mutant infections among local newborn babies.
DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: A
total of 137 newborn babies delivered between the period of November 2000 and 30
June 2001 inclusive, whose mothers were chronic hepatitis B surface antigen
carriers. RESULTS: Of the 121 infants who were followed up for 12 months, three
were found to be chronic hepatitis B virus carriers, giving a vertical
transmission rate of 2.5%. One (0.8%) was suspected to be infected by the S
mutant. All the three hepatitis B virus carrier babies were born to mothers with
hepatitis B e antigen, but none to the eight mothers suspected to have S-mutants.
Of 119 (98.3%) infants who developed hepatitis B surface antibody upon follow-up
at 12 months, 35 were found to have hepatitis B e antigen at birth. All were born
to hepatitis B e antigen-positive mothers. Only three of the 35 babies were found
to be hepatitis B virus carriers. Most babies lost the hepatitis B e antigen by 6
months of age; only the infected babies had the antigen persisting at 1 year of
age. The non-infected infants' hepatitis B e antigen is likely transplacental.
CONCLUSIONS: Our hepatitis B virus prophylaxis programme was effective at
preventing perinatal infection and the non-infected infants' hepatitis B e
antigen was likely transplacental.
PMID- 17028358
TI - Recurrent pneumothorax in pregnancy: what should we do after placing an
intercostal drain.
AB - Recurrent pneumothorax is rare during pregnancy. We describe a Chinese woman,
with a history of spontaneous pneumothorax managed with an intercostal drain, who
developed a recurrent pneumothorax during her 32nd week of pregnancy. There is no
consensus on management in this situation. We review the literature and discuss
different management approaches. Thirty-six cases of antepartum pneumothorax have
been reported in 31 case reports. An intercostal drain only (n=11) or surgeries
(thoracotomy, n=9; or video-assisted thoracoscopy, n=2) were common treatment
options with no surgical complications reported. Twenty-two (61%) patients
progressed to a normal vaginal delivery, while the rest required forceps delivery
(22%) or Caesarean section (14%). No single treatment option outweighed the
others. There were no maternal or foetal complications reported in those who
underwent antepartum surgical intervention. Surgical management of recurrent
pneumothorax during pregnancy is well tolerated.
PMID- 17028359
TI - Ex-utero intrapartum treatment: a controlled approach to the management of
anticipated airway problems in the newborn.
AB - Airway problems in an unborn foetus that may cause obstruction can be safely
managed using an ex-utero intrapartum technique. Advanced technology now allows
many congenital airway problems to be diagnosed in the prenatal period. Careful
prenatal planning of an ex-utero intrapartum treatment allows safe airway control
while the foetus remains on uteroplacental support. It avoids the need for
emergent intervention of an acutely obstructed airway in a neonate that often has
disastrous consequences.
PMID- 17028360
TI - Autoimmune polyendocrinopathy type II in a Chinese patient.
AB - Autoimmune polyendocrinopathy type II is rarely reported in Chinese patients. A
42-year-old Chinese woman with a history of Hashimoto's thyroiditis and
hypogonadotropic hypogonadism presented with pneumonia. During hospitalisation,
she went into an adrenal crisis and diabetic ketoacidosis. Subsequent dynamic
hormonal tests revealed primary and secondary adrenal insufficiency. She also had
pernicious anaemia, possible alopecia areata, and myasthenia gravis. This
constellation of multiple endocrine and non-endocrine disorders led to the
diagnosis of autoimmune polyendocrinopathy type II. As the syndrome can be
lethal, it is important to maintain a high index of suspicion, enabling early
diagnosis and the appropriate replacement therapy, to ensure a successful
outcome.
PMID- 17028361
TI - A case of takotsubo cardiomyopathy: transient left ventricular apical ballooning.
AB - A 78-year-old woman was admitted to hospital with central chest pain and the
electrocardiographic and cardiac marker changes typical of acute anterior
myocardial infarction. Coronary angiography revealed normal epicardial coronary
arteries, and left ventriculography showed apical akinesis as well as basal
hyperkinesis. This is a case of transient left ventricular apical ballooning or
takotsubo cardiomyopathy, possibly attributable to catecholamine-mediated
myocardial stunning.
PMID- 17028362
TI - Typhoid osteomyelitis of the lumbar spine.
AB - A 25-year-old Nepali man presented with a 20-day history of fever associated with
a lower backache. Physical examination found tenderness over the lower lumbar
vertebrae. Magnetic resonance imaging following intravenous contrast injection
showed enhancement of the L4 and L5 vertebrae, particularly pronounced around the
intervening disc, and areas of endplate erosion. Extra-vertebral enhancement and
a small subligamentous anterior collection were also noted. Computed tomography
guided needle aspiration was performed at the level of L4/5 disc material and
culture of the specimen grew Salmonella typhi sensitive to ampicillin,
ciprofloxacin, and ceftriaxone. The patient received intravenous ampicillin 2 g
per 4 hours for 6 weeks. The back pain resolved completely and the patient was
discharged. Typhoid osteomyelitis of the spine should be considered in the
differential diagnosis in patients from endemic areas who present with fever and
backache.
PMID- 17028363
TI - Acute renal failure associated with prolonged intake of slimming pills containing
anthraquinones.
AB - Chinese herbal medicine preparations are widely available and often regarded by
the public as natural and safe remedies for a variety of medical conditions.
Nephropathy caused by Chinese herbs has previously been reported, usually
involving the use of aristolochic acids. We report a 23-year-old woman who
developed acute renal failure following prolonged use of a proprietary Chinese
herbal slimming pill that contained anthraquinone derivatives, extracted from
Rhizoma Rhei (rhubarb). The renal injury was probably aggravated by the
concomitant intake of a non-steroidal anti-inflammatory drug, diclofenac. Renal
pathology was that of hypocellular interstitial fibrosis. Spontaneous renal
recovery occurred upon cessation of the slimming pills, but mild interstitial
fibrosis and tubular atrophy was still evident histologically 4 months later.
Although a causal relationship between the use of an anthraquinone-containing
herbal agent and renal injury remains to be proven, phytotherapy-associated
interstitial nephropathy should be considered in patients who present with
unexplained renal failure.
PMID- 17028364
TI - Unusual bleeding gastric ulcer.
PMID- 17028365
TI - Health professionals and the International Code of Marketing of Breast-milk
Substitutes.
PMID- 17028366
TI - Who founded WHO?
PMID- 17028369
TI - The genetics of autism spectrum disorders.
AB - Epidemiological twin studies demonstrate that autism spectrum disorders (ASDs)
represent genetic disorders. Subsequent analyses indicate that the causes of ASDs
include less common single-gene mutations and chromosomal abnormalities, as well
as ASDs caused by multiple interacting genes of weak effect. Genome-wide linkage
analysis has identified several susceptibility loci for the ASDs, and positional
and functional candidate genes have been identified that appear to represent
susceptibility genes for the ASDs. Analysis of additional larger samples and the
use of genome-wide association and high-throughput variant detection will lead to
the identification of further genes for ASDs.
PMID- 17028368
TI - Cerebral palsy.
AB - Cerebral palsy (CP) is a group of disorders of movement and posture resulting
from nonprogressive disturbances of the fetal or neonatal brain. More than 80% of
cases of CP in term infants originate in the prenatal period; in premature
infants, both prenatal or postnatal causes contribute. The most prevalent
pathological lesion seen in CP is periventricular white matter injury (PWMI)
resulting from vulnerability of the immature oligodendrocytes (pre-OLs) before 32
wk of gestation. PWMI is responsible for the spastic diplegia form of CP and a
spectrum of cognitive and behavioral disorders. Oxidative stress and
excitotoxicity resulting from excessive stimulation of ionotropic glutamate
receptors on preOLs are the most prominent molecular mechanisms for PWMI.
Asphyxia around the time of birth in term infants accounts for less than 15% of
CP in developed countries but the incidence is higher in underdeveloped areas.
Asphyxia causes a different pattern of brain injury and CP than is seen after
preterm injuries. This type of CP is associated with the clinical syndrome of
hypoxic-ischemic encephalopathy shortly after the insult, and the cortex, basal
ganglia, and brainstem are selectively vulnerable to injury. Experimental models
indicate that neurons in the neonatal brain are more likely to die by delayed
apoptosis extending over days to weeks than those in the adult brain. Neurons die
by glutamate-mediated excitotoxicity involving downstream caspase-dependent and
caspase-independent cell death pathways. Recent reports indicate that males and
females preferentially utilize different pathways. Clinical trials indicate that
mild hypothermia reduces death or disability in term infants following asphyxia
and basic research suggests that this approach might be combined with
pharmacological strategies in the future.
PMID- 17028371
TI - The molecular pathology of Rett syndrome: synopsis and update.
AB - Genetic mutations of the X-linked gene MECP2, encoding methyl-CpG-binding protein
2, cause Rett syndrome (RTT) and other neurological disorders. It is increasingly
recognized that MECP2 is a multifunctional protein, with at least four different
functional domains: (1) a methyl-CpG-binding domain; (2) an arginine-glycine
repeat RNA-binding domain; (3) a transcriptional repression domain; and (4) an
RNA splicing factor binding region (WW group II binding domain). There is
evidence that MECP2 is important for large-scale reorganization of
pericentromeric heterochromatin during differentiation. Studies in MECP2
deficient mouse brain have identified a diverse set of genes with altered levels
of mRNA expression or splicing. It is still unclear how altered MECP2 function
ultimately results in neuronal disease after a period of grossly normal
development. However, mounting evidence suggests that neuronal health and
development depend on precise regulation of MECP2 expression. In genetically
engineered mice, both increased and decreased levels of MECP2 result in a
neurological phenotype. Furthermore, it was recently discovered that MECP2 gene
duplications underlie a small number of atypical Rett cases and mental
retardation syndromes. The finding that MECP2 levels are tightly regulated in
neurons has important implications for the design of gene replacement or
reactivation strategies for treatment of RTT, because affected individuals
typically are somatic mosaics with one set of cells expressing a mutated MECP2
from the affected X, and another set expressing normal MECP2 from the unaffected
X. Further studies are necessary to elucidate the molecular pathology of both
loss-of-function and gain-of-function mutations in MECP2.
PMID- 17028370
TI - Attention deficit hyperactivity disorder.
AB - Attention deficit hyperactivity disorder (ADHD) is a behavioral diagnosis based
on the presence of developmentally inappropriate levels of impulsivity,
overactivity, and inattentiveness. It is a familial condition with a complex
pattern of inheritance. Variation of several genes involved in the regulation of
dopamine, norepinephrine, and serotonin neurotransmission is associated with
ADHD. We highlight the two most prominent findings with the dopamine D4 receptor
(DRD4) gene and the dopamine transporter (DAT1) gene, and their implications for
the understanding of the cellular and neurobiological basis for ADHD. Cognitive
and functional studies using electrophysiology and brain imaging frequently
indicate altered processing in ADHD during performance on cognitive tasks
hypothesized to measure a "core" deficit, such as response inhibition. Yet,
children with ADHD appear to suffer from a more general deficit, including
impairment in attentional alerting, orienting, response preparation, and control.
Reward processes are also altered and, further, a strong association emerges with
intraindividual variability, with several causal hypotheses being proposed. Task
performance correlates with underactivation of, especially, frontostriatal areas
of the brain, but an extended network of brain regions is also implicated.
Electroencephalography studies indicate abnormalities in ADHD in relation to slow
wave activity, linked to underarousal. These advances in the areas of genetics,
cognitive function, neurophysiology, and neuroanatomy of ADHD give important
leads for interdisciplinary research that aims to delineate the causal pathways.
Such research is only at its beginning, but is illustrated by recent findings of
an association between DAT1 and increased response variability in ADHD.
PMID- 17028372
TI - Ataxia-telangiectasia and related diseases.
AB - Appropriate cellular signaling responses to DNA damage and the ability to repair
DNA are fundamental processes that are required for organismal survival. Ataxia
telangiectasia (A-T) is a rare neurodegenerative disease that results from
defective DNA damage signaling. Understanding the molecular basis of A-T has
provided many critical insights into the cellular response to DNA double-strand
breaks (DSBs). A-T is a syndrome that shows pronounced neurodegeneration of the
nervous system coincident with immune deficiency, radiosensitivity, and cancer
proneness. A-T results from inactivation of the A-T mutated (ATM) kinase, a
critical protein kinase that regulates the response to DNA-DSBs by selective
phosphorylation of a variety of substrates. Therefore, understanding the ATM
signaling program has important biological ramifications for nervous system
homeostasis. Underscoring the importance of the DNA-DSBs response in the nervous
system are other diseases related to A-T that also result from defects in this
signaling pathway. In particular, defects in the DNA damage sensor, the Mre11
RAD50-NBS1 complex, also lead to syndromes with neurological deficits and
overlapping phenotypes to A-T. Collectively, these diseases highlight the
critical importance of appropriate responses to DNA-DSBs to maintain homeostasis
in the nervous system.
PMID- 17028373
TI - Kernicterus and the molecular mechanisms of bilirubin-induced CNS injury in
newborns.
AB - Kernicterus is a devastating, chronic disabling neurological disorder whose
central nervous system (CNS) sequelae reflect both a predilection of bilirubin
toxicity for neurons (rather than glial cells) and the regional topography of
bilirubin-induced neuronal injury that is characterized by prominent basal
ganglia, cochlear, and oculomotor nuclei involvement. The molecular pathogenesis
of bilirubin-induced neuronal cell injury, although incompletely understood,
likely reflects the untoward effects of hazardous unconjugated bilirubin
concentrations on plasma, mitochondrial, and/or endoplasmic reticulum (ER)
membranes. These membrane perturbations, in turn, might lead to the genesis of
neuronal excitotoxicity, mitochondrial energy failure, or increased intracellular
calcium concentration [Ca2+]i. These three phenomena are likely to be linked
spatially and temporally in the pathogenesis of bilirubin-induced neuronal
injury. Downstream events triggered by increased [Ca2+]i may include, among
others, the activation of proteolytic enzymes, apoptotic pathways, and/or
necrosis, the individual occurrence of which is likely a function of the degree
and duration of bilirubin exposure. A recent study demonstrates the activation of
mitogen-activated protein kinase signal transduction pathways by bilirubin
heralding a degree of complexity regarding the molecular mechanism(s) of
bilirubin-induced neurotoxicity not previously appreciated. There remains,
however, a paucity of data regarding specific effects of bilirubin on
intracellular signaling and cell death pathways, particularly in vivo. An
enhanced understanding of the molecular pathogenesis of bilirubin-induced
neuronal injury will lead to the identification of potential novel interventional
strategies to protect the CNS against kernicterus.
PMID- 17028374
TI - The neurobiology of the tuberous sclerosis complex.
AB - Tuberous sclerosis complex (TSC) is a multisystem disorder that affects numerous
organ systems. Brain lesions that form during development, known as tubers, are
highly associated with epilepsy, cognitive disability, and autism. Following the
identification of two genes and their encoded proteins, TSC1 (hamartin) and TSC2
(tuberin), responsible for TSC, identification of several downstream protein
cascades that might be affected in TSC have been discovered. Of primary
importance is the mammalian target of rapamycin pathway that controls cell growth
and protein synthesis. The mechanisms governing brain lesion growth have not been
fully identified but likely altered regulation of the mammalian target of
rapamycin cascade by hamartin and tuberin during development leads to aberrant
cell growth. Secondary effects of TSC gene mutations might disrupt normal
neuronal migration and cerebral cortical lamination. Numerous studies have
identified changes in gene and protein expression in animal models of TSC and in
human TSC brain specimens that contribute to altered brain cytoarchitecture. This
review will provide an overview of the neurobiological aspects of TSC.
PMID- 17028376
TI - Low Serum Selenium Is Associated with Anemia Among Older Women Living in the
Community: the Women's Health and Aging Studies I and II.
AB - Anemia is common among older adults, and a substantial proportion of anemia in
the older population is of indeterminate cause. Low selenium levels have been
associated with anemia in animals, but this relationship has not been well
characterized in humans. The objective was to determine whether low serum
selenium concentrations are associated with anemia among older women. We
conducted a cross-sectional analysis of participants in the Women's Health and
Aging Studies, a population-based sample of women living in the community in
Baltimore, MD, USA. Of 632 women, aged 70-79 yr, 14.1% of women were anemic
(hemoglobin <120 g/L). The prevalence of anemia among women in the lowest to
highest quartile of serum selenium was 22.4%, 14.6%, 11.9% and 6.6%, respectively
(p < 0.0001). An increase in loge selenium was associated with a reduced risk of
anemia (odds ratio per 1 SD increase = 0.63, 95% confidence interval = 0.47
0.84), adjusting for age, education, chronic diseases, iron status, and serum
interleukin-6. We conclude that low serum selenium is independently associated
with anemia among older women living in the community.
PMID- 17028377
TI - Effect of zinc supplementation on serum leptin levels and insulin resistance of
obese women.
AB - Leptin is thought to be a lipostatic signal that contributes to body weight
regulation. Zinc might play an important role in appetite regulation and its
administration stimulates leptin production. However, there are few reports in
the literature on its role on leptin levels in the obese population. The present
work assesses the effect of zinc supplementation on serum leptin levels in
insulin resistance (IR). A prospective double-blind, randomized, clinical,
placebo-controlled study was conducted. Fifty-six normal glucose-tolerant obese
women (age: 25-45 yr, body mass index [BMI] = 36.2 +/- 2.3 kg/m2) were randomized
for treatment with 30 mg zinc daily for 4 wk. Baseline values of both groups were
similar for age, BMI, caloric intake, insulin concentration, insulin resistance,
and zinc concentration in diet, plasma, urine, and erythrocytes. Insulin and
leptin were measured by radioimmunoassay and IR was estimated by the homeostasis
model assessment (HOMA). The determinations of zinc in plasma, erythrocytes, and
24- h urine were performed by using atomic absorption spectrophotometry. After 4
wk, BMI, fasting glucose, and zinc concentration in plasma and erythrocyte did
not change in either group, although zinc concentration in the urine increased
from 385.9 +/- 259.3 to 470.2 +/- 241.2 +/- microg/24 h in the group with zinc
supplementation (p < 0.05). Insulin did not change in the placebo group, whereas
there was a significant decrease of this hormone in the supplemented group. HOMA
also decreased from 5.8 +/- 2.6 to 4.3 +/- 1.7 (p < 0.05) in the zinc
supplemented group but did not change in the placebo group. Leptin did not change
in the placebo group. In the zinc group, leptin was 23.6 +/- 12.3 microg/L and
did not change. More human data from a unique population of obese individuals
with documented insulin resistance would be useful in guiding future studies on
zinc supplementation (with higher doses or longer intervals) or different
measures.
PMID- 17028378
TI - Dose-related influence of sodium selenite on apoptosis in human thyroid follicles
in vitro induced by iodine, EGF, TGF-beta, and H2O2.
AB - Apoptosis of thyroid follicular cells is induced by high doses of iodide,
epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), as
well as H2O2 and might be attenuated by antioxidants. Therefore, we examined the
apoptotic index induced by these substances in selenium-treated vs untreated
human thyroid follicular cells. Reconstituted human thyroid follicles were
incubated with sodium selenite (10 or 100 nM) for 72 h; controls received none.
The follicles were then distributed to 24-well plates and incubated with
potassium iodide (5, 10, or 20 nM), EGF (5 ng/mL), TGF-beta (5 ng/mL), or H2O2
(100 muM). Apoptosis was determined by a mitochondrial potential assay and the
number of apoptotic cells counted by two independent, experienced technicians and
the glutathione peroxidase (GPx) activity was determined. Asignificant increase
of apoptic cells was obtained in control thyroid follicles treated with iodine
(5, 10, or 20 microM), thyroidstimulating hormone (TSH) 1, or 10 mU/mL in
combination with 5 and 10 microM iodine, EGF (5 ng/mL) and TGF-beta (5 ng/mL), or
H2O2 (100 microM) (p < 0.001). In contrast, in thyroid follicles preincubated
with 10 or 100 nM sodium selenite, the apoptototic index was identical to the
basal rate. In H2O2-treated follicles, the apoptotic index was still
significantly elevated but 50% lower compared to control cells. The GPx activity
increased from 1.4 +/- 0.2 to 2.25 +/- 0.4 mU/microg DNA with 10 nMselenite and
2.6 + 0.4 mU/microg DNA with 100 nM selenite. Sodium selenite might increase the
antioxidative potential in human thyroid follicles in vitro and therefore
diminish the apoptosis induced by TGF-beta, EGF, iodide, and even H2O2.
PMID- 17028375
TI - Lissencephaly 1 linking to multiple diseases: mental retardation,
neurodegeneration, schizophrenia, male sterility, and more.
AB - Lissencephaly 1 (LIS1) was the first gene implicated in the pathogenesis of type
1 lissencephaly. More than a decade of research by multiple laboratories has
revealed that LIS1 is a key node protein, which participates in several pathways,
including association with the molecular motor cytoplasmic dynein, the reelin
signaling pathway, and the platelet-activating factor pathway. Mutations in LIS1
interacting proteins, either in human, or in mouse models has suggested that LIS1
might play a role in the pathogenesis of numerous diseases such as male
sterility, schizophrenia, neuronal degeneration, and viral infections.
PMID- 17028379
TI - Blood alpha-Tocopherol, selenium, and glutathione peroxidase changes and adipose
tissue fatty acid changes in kittens with experimental steatitis (yellow fat
disease): a comparative study between the domestic shorthaired and Siamese breed.
AB - Twenty domestic shorthaired (DSH) and 20 Siamese (S) kittens were allocated into
4 breed-specific groups, of 10 kittens each, that were fed exclusively cooked
sardines (F groups) or commercial feline canned food based on oily fish (C
groups) for a 4-month period. Clinical signs were scored every 15 d along with
body weight recording and blood sampling for the measurement of alpha-tocopherol
and selenium (Se) concentrations and glutathione peroxidase (GSH-Px) activity.
Subcutaneous adipose tissue samples were obtained per month to determine its
fatty acid composition. Steatitis, reproduced in all 20 F-group kittens, was
accompanied by systemic signs in 5 DSH and 6 S animals. The severity of the
disease reached its zenith at the second week in the DSH-F-group kittens and the
fourth and sixth week in the S-F-group kittens. alpha-Tocopherol plasma level was
significantly lower in F groups compared to their corresponding controls, whereas
the opposite was true for Se and red blood cell GSH-Px activity. In conclusion,
the results of this study have shown that although the morbidity rate is not
different between the two breeds, the delay of Siamese cats to develop
symptomatic steatitis is presumably attributed to an inherent resistance as a
result of the long-standing evolution of more efficient antioxidant mechanisms.
Also, the changes in fatty acid composition of the adipose tissue lipids are
associated with the progression of the age, breed, and diet and probably with the
inflammatory changes of the adipose tissue.
PMID- 17028380
TI - Effect of dietary zinc on the levels and distribution of Fatty acids and vitamin
A in blood plasma chylomicrons.
AB - The aim of this work was to explore the effects of a low- and high-zinc diet and
vitamin Aon the distribution of fatty acids in chylomicrons. Mongolian Gerbils
were fed a basal diet (for 3 wk) containing 8 or 38 mg zinc/kg of feed (low-zinc
group [termed LZ group] and saturated zinc group [termed SZ group],
respectively). The following day, the animals were given sunflower oil containing
50 nmol vitamin A. The results showed that the concentration of zinc in blood
plasma was similar in both groups. The amount of plasma chylomicrons was lower in
the LZ group than in the SZ group (p < 0.001). The concentration of retinol in
blood plasma was lower in the LZ group than in the SZ group (p < 0.01). However,
the results demonstrated an increase in the blood plasma retinol concentration in
the LZ group compared to the SZ group when calculated per milligram of plasma
chylomicrons (p < 0.01). In plasma chylomicrons, fatty acids corresponding to
16:0, 16:1, 17:0, 17:1, 18:0, 18:1, 18:2, 18:3, 20:0, 21:0, and 20:4 were
detected. The fatty acid distribution was similar in both groups. There was no
major difference in the concentration of fatty acids in plasma chylomicrons
between both experimental groups, except for 20:4 (a lower amount was found in
the SZ group). Our results show that dietary zinc influences both the amount of
chylomicrons in blood plasma and the concentrations of retinol and arachidonic
acid in chylomicrons.
PMID- 17028381
TI - Correlation between ZIP2 messenger RNA expression and zinc level in rat lateral
prostate.
AB - Zinc content in rat lateral prostate (LP) is higher compared with the other
tissues, but the zinc retention system in the prostate remains unclear. In the
present study, we examined the expression of ZRT, a IRT-like protein (ZIP) family
transporter in rat prostate. The zinc level in rat LP was higher compared with
the ventral (VP) and dorsal prostate (DP). The predicted ZIP2 mRNA was really
expressed in LP at a high level. The expression was decreased in LP from
castrated rats, associated with a decrease in zinc level, and these changes were
prevented by testosterone replacement. Moreover, ZIP2 expression levels in LP
positively correlated with the zinc levels. These findings strongly suggest that
ZIP2 is involved in zinc homeostasis of rat prostate.
PMID- 17028382
TI - Influence of sodium fluoride and caffeine on the concentration of fluoride ions,
glucose, and urea in blood serum and activity of protein metabolism enzymes in
rat liver.
AB - The aim of the study was examining the effect of fluoride ions and caffeine
administration on glucose and urea concentration in blood serum and the activity
of protein metabolism enzymes and selected enzymes of the urea cycle in rat
liver. The study was carried out using 18 male Sprague-Daowley rats (4.5 mo old).
Rats were divided into three groups. Group I received distilled water ad libitum.
Group II received 4.9 mg F-/kg body mass/d of sodium fluoride in the water, and
group III received sodium fluoride (in the above-mentioned dose) and 3 mg/kg body
mass/d of caffeine in the water. After 50 d, the rats were anesthetized with
thiopental and fluoride ions, glucose, and urea concentration in blood serum were
determined. Also determined were the activities of aspartate aminotransferase,
alanine aminotransferase glutamate dehydrogenase, ornithine carbamoylotransferase
and arginase in liver homogenates. Liver was taken for pathomorphological
examinations. The applied doses of F- (4.9 mg/kg body mass/d) and F- + caffeine
(4.9 mg F-/kg body mass/d + 3 mg caffeine/kg body mass/d) resulted in a
statistically significant increase of fluoride ion concentration in blood serum,
a slight increase of the glucose concentration, and no changes in the
concentration of urea in blood serum. This might testify to the absence of kidney
lesions for the applied concentrations of F-. No change in the functioning of
hepatocytes was observed; however, slight disturbances have been noted in the
functioning of the liver, connected with the activation of urea cycle, increase
of arginase activity, and accumulation of F- in this organ. There was no observed
significant influence of caffeine supplementation on the obtained results.
PMID- 17028383
TI - Influence of silicon on cobalt, zinc, and magnesium in baker's yeast,
Saccharomyces cerevisiae.
AB - Silicon (Si, as silicate) is involved in numerous important structure and
function roles in a wide range of organisms, including man. Silicate availability
influences metal concentrations within various cell and tissue types, but, as
yet, clear mechanisms for such an influence have been discovered only within the
diatoms and sponges. In this study, the influence of silicate on the
intracellular accumulation of metals was investigated in baker's yeast
(Saccharomyces cerevisiae). It was found that at concentrations up to 10 mM,
silicate did not influence the growth rate of S. cerevisiae within a standard
complete medium. However, an 11% growth inhibition was observed when silicate was
present at 100 mM. Intracellular metal concentrations were investigated in yeast
cultures grown without added silicate (-Si) or with the addition of 10 mM
silicate (+Si). Decreased amounts of Co (52%), Mn (35%), and Fe (20%) were found
within +Sigrown yeast cultures as compared to -Si-grown ones, whereas increased
amounts of Mo (56%) and Mg (38%) were found. The amounts of Zn and K were
apparently unaffected by the presence of silicon. +Si enhanced the yeast growth
rate for low-Zn2+ medium, but it decreased the growth rate under conditions of a
low Mg2+ medium and did not alter the growth rates in high Zn2+ and Co2+ media.
+Si doubled the uptake rate of Co2+ but did not influence that of Zn2+. We
propose that a possible explanation for these results is that polysilicate
formation at the cell wall changes the cell wall binding capacity for metal ions.
The toxicity of silicate was compared to germanium (Ge, as GeO2), a member of the
same group of elements as Si (group 14). Hence, Si and Ge are chemically similar,
but silicate starts to polymerize to oligomers above 5 mM, whereas Ge salts
remain as monomers at such concentrations. Ge proved to be far more toxic to
yeast than Si and no influence of Si on Ge toxicity was found. We propose that
these results relate to differences in cellular uptake.
PMID- 17028389
TI - [Familial subtelomeric abnormality der(4)t(4p16.3;21q22.3) as a cause of mental
retardation and mild dysmorphic features].
AB - A 3-year-old girl with developmental delay, dysmorphic features, hypotonia and
microcephaly is presented. Fluorescence in situ hybridization (FISH) with
subtelomeric probes (Multiprobe Chromoprobe T System) revealed monosomy and
trisomy of subtelomeric regions 4p and 21q respectively. Clinical and pedigree
data were analyzed and the phenotype -genotype correlation for partial monosomy
4p and trisomy 21q identified in the proband is also presented.
PMID- 17028390
TI - [Characterization of marker chromosomes using molecular cytogenetic methods in
patients with mental retardation and congenital malformations].
AB - INTRODUCTION: Until recently, great variety of marker chromosomes and
difficulties with their identification have presented a problem for cytogenetic
and clinical interpretation of the karyotype. At present, molecular cytogenetic
methods of chromosome analysis enable precise characterization of such
abnormalities providing knowledge necessary for estimation of their genetic risk.
AIM: The aim of the study was molecular cytogenetic characterization of marker
chromosomes recognized in three patients, an analysis of clinical features in
relation to the abnormality and estimation of genetic risk of identified markers.
PATIENTS AND METHODS: Karyotypes of three phenotypically abnormal patients were
estimated in lymphocytes from peripheral blood by G banding analysis. Marker
chromosomes were identified by fluorescence in situ hybridization (FISH),
multiplex FISH, multicolor band and high resolution comparative genomic
hybridization methods. RESULTS: Marker chromosomes were identified as inv
dup(22)(pter->q11.2::q11.2->pter), der(8)(:p22->q11.2:), der(2l)(:pter->q21.3:)
and der(19)(:p11->q13.1). All of them contained euchromatic sequences. First
marker, an inverted duplication of chromosome 22q11.2 corresponding to tetrasomy
of this chromosome region was recognized in a child with partial cat eye
syndrome. Two further markers derived from chromosomes 8 and 21 were found in a
child with mosaic karyotype and clinical features of trisomy 8p. In the third
case additional chromosome material was derived from chromosome 19 and it was
found in a patient with mild mental retardation and clinical features of ovary
dysgenesis. Genetic risk of identified marker chromosomes except for mar(19) was
estimated as high. CONCLUSIONS: Our results provide further evidence for
diagnostic value of molecular cytogenetic methods. They also confirmed the
general opinion of the high risk of phenotypic abnormalities in the carriers of
marker chromosomes containing euchromatic sequences.
PMID- 17028391
TI - [Cytogenetic-molecular analysis of balanced chromosomal rearrangements in nine
patients with intellectual disability, dysmorphic features and congenital
abnormalities].
AB - INTRODUCTION: In about 6% of individuals with intellectual disability, dysmorphic
features and congenital anomalies, an abnormal, apparently balanced karyotype is
found. These abnormalities may result from abnormal expression of genes at the
breakpoints, presence of a submicroscopic deletion, or other unbalanced
chromosome aberrations. In such cases, the detailed analysis of breakpoints of
balanced chromosome rearrangements may help with identification of genes
responsible for patient's clinical features. AIM OF WORK: Was the explanation of
causes of abnormal phenotype in the carriers with abnormal but balanced
karyotype. MATERIAL AND METHODS: Cytogenetic-molecular analysis performed in nine
patients with mental retardation, dysmorphic features and congenital anomalies.
Studies with subtelomeric probes, high resolution comparative genomic
hybridization (HR-CGH) and fluorescence in situ hybridization (FISH) with region
specific BAC clones were performed. RESULTS: Seventeen chromosome breakpoint
regions were narrowed to 200-400 kb. In one case, an 0.5-Mb submicroscopic
deletion associated with more complex rearrangement has been found. Mapping of
the breakpoints and information obtained from the UCSC Human Genome Browser data
base enabled identification of 46 genes in these regions. Twelve genes, that may
have been disrupted as a result of the patients' chromosomal rearrangement, were
found. At four different breakpoints the identified genes (NRCAM, NPTX1, NMT1,
MAPT, HDAC5 and MEF2C) may be due to a position effect. CONCLUSIONS: The results
confirm earlier suggestions concerning reasons of abnormal phenotype in the
patients with balanced chromosome rearrangements and present the value of
detailed analysis of the genome in such cases.
PMID- 17028392
TI - [On the way to gene therapy in cystic fibrosis].
AB - Cystic fibrosis (CF) is the most common recessively inherited lethal disease
among the Caucasian population. CF is caused by mutations in the CFTR gene.
Although several organs and tracts are affected, severe lung disease is the cause
of the most of the morbidity and mortality in CF individuals. Current treatment
is aimed at slowing the inevitable progression of lung disease, rather than
halting it, or preventing its onset. The isolation of the gene responsible for CF
suggested the feasibility of new therapeutic possibilities based on the CFTR gene
transfer to CF patients. At present, somatic CF gene therapy clinical trials,
using mostly animals but also CF patients, are being conducted. Gene therapy
development is restricted by the lack of the appropriate gene vector systems,
which could be successfully used to transfer in vivo and protect the therapeutic
gene. This is because of the many extracellular, intracellular and immunological
barriers, which protect living organisms against invasion of foreign genetic
material. Future improvement in gene therapy depends on the more effective ways
of the gene transfer methods, creation animal models of the human diseases and
development of strategies involved in the new gene construct formulation, which
facilitate to control gene transcription activity.
PMID- 17028393
TI - [Genetic markers in the pathogenesis of osteopenia and osteoporosis in cystic
fibrosis].
AB - Cystic fibrosis (CF) is the most common recessive autosomal disorder in the
Caucasian population. Advancements in treatment of CF patients have increased
life expectancy from approximately 2 to over 30 years. Complex approach to the
health status and management of CF children increased the interest in
osteoarticular system pathology in these patients. This particularly concerns
osteopenia and osteoporosis. Multiple studies indicate that osteoporosis is a
genetic disease in which the phenotype is determined by both environmental and
genetic factors and by mutual interactions between them. It is postulated that
osteoporosis occurs as the result of mutations and/or polymorphisms in many
different genes. The evidence for the genotype-phenotype correlation came from
the analysis of mutations and polymorphisms in Collagen Type I Alpha 1 (COL1A1),
Vitamin D Receptor (VDR) and Calcitonin receptor (CALCR) genes. Determination of
osteoporotic genetic background may lead to better understanding of the
pathomechanism of osteoporosis in CF patients and to help further define
treatment guidelines.
PMID- 17028394
TI - [Clinical symptoms and molecular pathogenesis of Noonan syndrome--current
concepts].
AB - Noonan syndrome (NS; MIM 163950) is an autosomal dominant disorder. With
incidence of 1/1000 to 1/2500 live births, NS belongs to the most common genetic
disorders. Typical features of NS are: short stature, chest deformities,
congenital heart defects, cryptorchidism and dysmorphic features. Mutations of
PTPN11 gene (located on chromosome 12q24.1) are responsible for NS and are
identified in 33-60% cases. Less than half of the cases are familial. This paper
presents current opinion on clinical symptoms, molecular pathogenesis and
possibilities of growth hormone therapy. The genotype--phenotype correlation is
also discussed.
PMID- 17028395
TI - [Primary torsion dystonia--clinical and molecular aspects].
AB - Dystonias are a heterogeneous group of neurological disorders. In this paper we
present clinical and molecular characteristics of inherited primary torsion
dystonias. Clinical data and current concepts on the pathogenesis of dystonias
with known molecular defect are presented in detail. Therapeutic options in
patients with primary dystonias are also discussed.
PMID- 17028396
TI - [Identification of immunoglobulin and T-cell receptor gene rearrangements-
prerequisite for monitoring of minimal residual disease in Polish acute
lymphoblastic leukemia patients based on European standards. Preliminary
results].
AB - OBJECTIVE: Initiation and popularization of routine molecular diagnostics of
minimal residual disease (MRD) are currently one of the most urgent challenges in
Polish hemato-oncology. The paper is aimed to present preliminary results of
identification of immunoglobulin (Ig) and T-cell receptor (TCR) gene
rearrangements and quantitative assessment of MRD levels in Polish children with
acute lymphoblastic leukemia (ALL). The results are presented in the context of
clinical significance of MRD study, current methodology of MRD assessment and
standardization process in Western Europe. MATERIAL: DNA isolated from bone
marrow / bone marrow mononuclear cells obtained at diagnosis from 26 children (25
B-precursor ALL, 1 T-ALL) aged 1.3-16.5 years. METHODS: PCR-heteroduplex
analysis, based on standard BIOMED-1 and BIOMED-2 primer combinations and
protocols for detection of rearrangements and clonality assessment; sequencing of
clonal PCR products and comparison with germline sequences of Ig/TCR genes for
identification of the rearranged genes andjunctional regions; real-time
quantitative PCR (RQ-PCR) with the use of TaqMan probes for assessment of follow
up MRD levels (in 11 patients). RESULTS: Clonal TCRG, incomplete TCRD, Vdelta2
Jalpha, TCRB, IGK-Kde and IGH gene rearrangements were detected in 61, 61, 35,
13, 39 and 83% of patients, respectively, which was generally concordant with
published data for patients of other European nations. CONCLUSIONS: There is an
urgent need to broaden the scope of minimal residual disease study in Poland and
to develop Polish standards of MRD diagnostics, based on current European
experience and standards.
PMID- 17028397
TI - [Pathogenic mutation or polymorphism? (How to find criteria)].
AB - The classification of amino-acid substitutions into pathogenic mutations and
harmless polymorphisms should be revised. In the recent years it was shown that
some amino-acid substitutions considered as pathogenic mutations were
polymorphisms. Similarly, some 'harmless' polymorphisms have been shown to be
pathogenic mutations. Functional analysis considered as a good method to estimate
the pathogenic nature of mutations is also limited. The selection of DNA samples
for the control group is also difficult. Due to the molecular mechanism mediated
by recently discovered exonic splicing enhancers and silencers (ESE and ESS) it
is hard to predict a pathogenic effect of some mutations. In addition, the
phenotype variability observed between unrelated patients harboring the same
mutation may reflect the effects of modifying genes as well as the lack of
association between mutation and "its" phenotype. The aim of this study is to
describe the problem of the pathogenic effect of mutations.
PMID- 17028398
TI - [Attention deficit hyperactivity disorder (ADHD)--molecular and genetic aspects].
AB - Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral
disorder of childhood, affecting approximately 5-10% of children. ADHD is
considered to be a multifactorial disorder because both genetic and environmental
components may contribute to its progress. The etiology of attention deficit
hyperactivity disorder (ADHD) is unknown, however family, twin and adoption
studies have suggested that genetic factors are very important in its
etiopathogenesis. The research of genetic basis of ADHD consists of linkage
analysis, candidate gene approach and association studies. These analyses and
also investigations on animal models of disease suggest that mutations in genes
involved in dopaminergic, serotonergic and adrenergic systems are likely to be
responsible for ADHD.
PMID- 17028399
TI - [Hutchinson-Gilford progeria in the light of contemporary genetics].
AB - Hutchinson-Gilford progeria causing premature aging of children is a genetic
disease and according to most authors has an autosomal dominant inheritance. It
has been regarded as a model of the process of aging. In 2003 mutations in the
LMNA gene, localized f in chromosome 1, responsible for the disease, were
identified. The most frequent mutation is located in exon 11, C1824T and does not
change glycin in position 608 of protein chain, but activates cryptic splice
site. This results in shortened lamin A synthesis which is named progerin. Point
mutations in other exons of LMNA, found in progeria patients, are responsible for
atypical phenotypes.
PMID- 17028400
TI - [Carrier detection in Duchenne/Becker muscular dystrophy in the families in which
the DNA of the affected person is not available].
AB - INTRODUCTION: Duchenne muscular dystrophy (DMD) is a severe, progressive, X
linked muscular disease, which affects 1 in 3500 male newborns. The course of the
other allelic form of the disease (Becker muscular dystrophy--BMD) is milder.
Female relatives of affected subjects may carry the mutated gene. AIM OF THE
STUDY: The purpose of this study was to detect the carrier among 23 families
affected with DMD/BMD, in whom DNA from the deceased affected person was not
available. MATERIAL AND METHODS: The analysis of polymorphic sequences within the
dystrophin gene was applied. RESULTS: Informative results were obtained in 26 of
39 females examined (66%): 7 females were found to be carriers and 19
noncarriers. In one family the deletion could be detected in the mother and
sister of the deceased proband.
PMID- 17028401
TI - An adaptive input-output modeling approach for predicting the glycemia of
critically ill patients.
AB - In this paper we apply system identification techniques in order to build a model
suitable for the prediction of glycemia levels of critically ill patients
admitted to the intensive care unit. These patients typically show increased
glycemia levels, and it has been shown that glycemia control by means of insulin
therapy significantly reduces morbidity and mortality. Based on a real-life
dataset from 15 critically ill patients, an initial input-output model is
estimated which captures the insulin effect on glycemia under different settings.
To incorporate patient-specific features, an adaptive modeling strategy is also
proposed in which the model is re-estimated at each time step (i.e., every hour).
Both one-hour-ahead predictions and four-hours-ahead simulations are executed.
The optimized adaptive modeling technique outperforms the general initial model.
To avoid data selection bias, 500 permutations, in which the patients are
randomly selected, are considered. The results are satisfactory both in terms of
forecasting ability and in the clinical interpretation of the estimated
coefficients.
PMID- 17028402
TI - Pseudo-polar drive patterns for brain electrical impedance tomography.
AB - Brain electrical impedance tomography (EIT) is a difficult task as brain tissues
are enclosed by the skull of high resistance and cerebrospinal fluid (CSF) of low
resistance, which makes internal resistivity information more difficult to
extract. In order to seek a single source drive pattern that is more suitable for
brain EIT, we built a more realistic experimental setting that simulates a head
with the resistivity of the scalp, skull, CSF and brain, and compared the
performance of adjacent, cross, polar and pseudo-polar drive patterns in terms of
the boundary voltage dynamic range, independent measurement number, total
boundary voltage changes and anti-noise performance based on it. The results
demonstrate that the pseudo-polar drive pattern is optimal in all the aspects
except for the dynamic range. The polar and cross drive patterns come next, and
the adjacent drive pattern is the worst. Therefore, the pseudo-polar drive
pattern should be chosen for brain EIT.
PMID- 17028403
TI - Investigation of fall-risk using a wearable device with accelerometers and rate
gyroscopes.
AB - A clinical tool and an associated test that can assess fall-risk in elderly
patients have been designed. The clinical tool was based on a wearable device
with accelerometers and rate gyroscopes to identify trunk kinematic parameters.
The test was based on a posturography protocol with different constraints and
statistical analysis of the kinematic parameters. Statistical clustering based on
the Mahalanobis distance was carried out using three groups of 30 subjects (1,
age < 65 years; 2, age > or = 65 years and 3, age > or = 65 years and a fall
history). The method was statistically validated using three groups of 100
subjects. The test allowed discrimination of elderly subjects with a high fall
risk with high specificity > or = 0.930 and sensitivity > or = 0.939.
PMID- 17028404
TI - Analysis of electroencephalograms in Alzheimer's disease patients with multiscale
entropy.
AB - The aim of this study was to analyse the electroencephalogram (EEG) background
activity of Alzheimer's disease (AD) patients using multiscale entropy (MSE). MSE
is a recently developed method that quantifies the regularity of a signal on
different time scales. These time scales are inspected by means of several coarse
grained sequences formed from the analysed signals. We recorded the EEGs from 19
scalp electrodes in 11 AD patients and 11 age-matched controls and estimated the
MSE profile for each epoch of the EEG recordings. The shape of the MSE profiles
reveals the EEG complexity, and it suggests that the EEG contains information in
deeper scales than the smallest one. Moreover, the results showed that the EEG
background activity is less complex in AD patients than control subjects. We
found significant differences between both subject groups at electrodes F3, F7,
Fp1, Fp2, T5, T6, P3, P4, O1 and O2 (p-value < 0.01, Student's t-test). These
findings indicate that the EEG complexity analysis performed on deeper time
scales by MSE may be a useful tool in order to increase our knowledge of AD.
PMID- 17028405
TI - Wound measurement by curvature maps: a feasibility study.
AB - A non-contact wound measurement method by laser scanner and curvature maps is
presented. A patient's foot ulcer is scanned by FastSCAN ten times over a three
week period. With the surface's 3D coordinates, curvature maps of the ulcerous
area are calculated. Utilizing a specified rim curvature value, the wound edge is
detected and processed via cubic spline smoothing, which is qualitatively
verified by a photograph. Subsequently, the depth, area and volume of the wound
can be calculated. The results indicate that laser scanning followed by curvature
analysis might be a potential clinical tool for non-contact measurement of
wounds.
PMID- 17028406
TI - Simulation of Brugada syndrome using cellular and three-dimensional whole-heart
modeling approaches.
AB - Brugada syndrome (BS) is a genetic disease identified by an abnormal
electrocardiogram (ECG) (mainly abnormal ECGs associated with right bundle branch
block and ST-elevation in right precordial leads). BS can lead to increased risk
of sudden cardiac death. Experimental studies on human ventricular myocardium
with BS have been limited due to difficulties in obtaining data. Thus, the use of
computer simulation is an important alternative. Most previous BS simulations
were based on animal heart cell models. However, due to species differences, the
use of human heart cell models, especially a model with three-dimensional whole
heart anatomical structure, is needed. In this study, we developed a model of the
human ventricular action potential (AP) based on refining the ten Tusscher et al
(2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573-89) model to incorporate
newly available experimental data of some major ionic currents of human
ventricular myocytes. These modified channels include the L-type calcium current
(I(CaL)), fast sodium current (I(Na)), transient outward potassium current
(I(to)), rapidly and slowly delayed rectifier potassium currents (I(Kr) and
I(Ks)) and inward rectifier potassium current (I(Ki)). Transmural heterogeneity
of APs for epicardial, endocardial and mid-myocardial (M) cells was simulated by
varying the maximum conductance of I(Ks) and I(to). The modified AP models were
then used to simulate the effects of BS on cellular AP and body surface
potentials using a three-dimensional dynamic heart-torso model. Our main findings
are as follows. (1) BS has little effect on the AP of endocardial or mid
myocardial cells, but has a large impact on the AP of epicardial cells. (2) A
likely region of BS with abnormal cell AP is near the right ventricular outflow
track, and the resulting ST-segment elevation is located in the median precordium
area. These simulation results are consistent with experimental findings reported
in the literature. The model can reproduce a variety of electrophysiological
behaviors and provides a good basis for understanding the genesis of abnormal ECG
under the condition of BS disease.
PMID- 17028407
TI - Quantification of the timing of continuous modulated muscle activity in a
repetitive-movement task.
AB - The timing of muscle activity is commonly measured in studies of motor control.
In repetitive-movement tasks, muscle activity may be continuous, and no defined
onset or offset of activity may be measured. This does not imply that no timing
of muscle activity occurs. Where activity is continuous, this timing will
typically be exhibited by modulation of the amplitude of the signal in specific
movement phases. The existence of this electromyographic (EMG) timing is
dependent upon the existence of EMG amplitude modulation. This paper investigates
this relationship in developing a quantification algorithm of EMG timing in a
repetitive-movement task. A frequency domain quantification algorithm involving
EMG linear-envelope generation is used. An EMG simulation algorithm is used to
test this algorithm and determine the minimal amplitude-modulation threshold for
timing detection. At five repetitive-movement speeds (25, 50, 75, 100 and 125
cycles of movement per minute), thresholds between 1.558 and 2.326 times maximal
to minimal linear-envelope amplitude are required for reliability of timing
detection. Analysis of variance indicates that the robustness of the
quantification algorithm was not significantly affected by burst width (F = 3.69,
p = 0.055) or the underling input timing parameter (F = 0.52, p = 0.992). The
phase-lead/lag quantification algorithm represents a useful tool for the analysis
motor control via EMG during repetitive-movement tasks.
PMID- 17028408
TI - Electrical impedance tomography in extremely prematurely born infants and during
high frequency oscillatory ventilation analyzed in the frequency domain.
AB - Functional electrical impedance tomography (EIT) measures relative impedance
change that occurs in the chest during a distinct observation period and an EIT
image describing regional relative impedance change is generated. Analysis of
such an EIT image may be erroneous because it is based on an impedance signal
that has several components. Most of the change in relative impedance in the
chest is caused by air movement but other physiological events such as cardiac
activity change in end expiratory level or pressure swings originating from a
ventilator circuit can influence the impedance signal. We obtained EIT images and
signals in spontaneously breathing healthy adults, in extremely prematurely born
infants on continuous positive airway pressure and in ventilated sheep on
conventional mechanical or high frequency oscillatory ventilation (HFOV). Data
were analyzed in the frequency domain and results presented after band pass
filtering within the frequency range of the physiological event of interest. Band
pass filtering of EIT data is necessary in premature infants and on HFOV to
differentiate and eliminate relative impedance changes caused by physiological
events other than the one of interest.
PMID- 17028409
TI - Evaluation of renal functional parameters in different settings of isolated organ
hemoperfusions.
AB - Isolated porcine kidneys are commonly used to study physiological and
pathophysiological aspects of renal homeostasis but standardized evaluation
procedures of renal function in this model do not exist so far. A double
logarithmical nomogram is established for filtration and reabsorption functions
in isolated and hemoperfused porcine kidneys using different perfusion settings.
Model validity was demonstrated by the levels of urine flow and sodium excretion
showing expected alteration levels of lowering in the ADH-group and increasing in
the furosemide-group of isolated kidneys. Creatinine-clearance values were in
constant ranges within each specific perfusion group as indicated by the nomogram
procedure. The present studies used a nomogram method to analyze the effects of
different renal perfusion settings in a porcine model of kidney perfusion. The
method may be of use to differentiate various kidney perfusion parameters both at
the experimental and clinical levels.
PMID- 17028410
TI - Reference values for whole body and cerebral multi-frequency bio-impedance data
in neonates less than 12 h postpartum.
AB - Multiple frequency bio-electrical impedance analysis (MFBIA) may be useful for
monitoring fluid balance in newborn infants or to provide early prediction of the
outcome following perinatal asphyxia. A reference range of data is needed for
identification of babies with abnormal impedance values. This was a cross
sectional observational study in 84 term and near-term healthy neonates less than
12 h postpartum. Whole body and cerebral MFBIA measurements were performed at the
bedside in the post-natal ward. Gestational age, post-natal age, gender,
birthweight, head circumference and foot length measures were recorded. Reference
values for impedance at the characteristic frequency (Z(C)) and resistance at
zero frequency (R(0)) are reported for whole body and cerebral impedance.
Significant correlations (p < 0.05) were observed between whole body impedance
and birthweight, footlength and head circumference. Females had a significantly
higher whole body R(0) than males. Cerebral impedance did not correlate
significantly with any of the demographic measures and there were no gender
differences observed for cerebral impedance. The reference range for whole body
multi-frequency bio-impedance values in term and near-term infants within the
first 12 h postpartum can be calculated from the footlength (FL) using the
following equations: Z(C) = (942.9 - 4.818*FL) +/- 124.6 Omega; R(0) = (1042 -
4.520*FL) +/- 135.5 Omega. For cerebral impedance the reference range is 29.5
48.7 Omega for Z(C) and 33.7-58.0 Omega for R(0).
PMID- 17028411
TI - Real-time trace gas sensing of ethylene, propanal and acetaldehyde from human
skin in vivo.
AB - Trace gases emitted by human skin in vivo are monitored non-invasively and in
real time using laser-based photoacoustic detection and proton-transfer reaction
mass spectrometry. A small quartz cuvette is placed on the skin to create a
headspace from which a carrier gas transports the skin emissions to the detection
systems. The transparency of quartz to ultraviolet radiation (UVR) allows
investigation of UVR-related trace gas emissions. As a demonstration of this
measurement system, the effect of supplemental intake of systemic antioxidants on
UVR-induced lipid peroxidation is investigated. The production by the skin of
three biomarkers of UVR-induced lipid peroxidation (ethylene, acetaldehyde and
propanal) is monitored. Although no significant effect of antioxidant intake was
observed, the method presented here is a novel and promising technique for
investigation of human skin in vivo.
PMID- 17028412
TI - Effect of body surface area calculations on body fat estimates in non-obese and
obese subjects.
AB - The purpose of the present study was to compare body surface area (BSA) estimates
using two equations (Dubois and Dubois versus Livingston) and their respective
effects on per cent body fat (%BF) obtained with two molecular approaches of body
composition analysis, two-compartment (2C) and five-compartment (5C) models. Body
composition data using the 2C model were studied in healthy adults, 432 women
(body mass index (BMI): 28.3 +/- 4.4 kg m(-2)) and 147 men (BMI: 26.8 +/- 3.9 kg
m(-2)), while another sample of 126 women (BMI: 30.4 +/- 3.7 kg m(-2)) was
evaluated using the 5C model. Measures of body volume (BV) assessed by air
displacement plethysmography, bone mineral content by dual energy x-ray
absorptiometry (DXA) and total-body water by deuterium dilution were used to
estimate %BF with the 5C model. Comparison of means and linear regression
analysis was performed. Using BSA(Dubois), either in 2C and 5C models, BV and %BF
estimates were significantly underestimated compared to results obtained using
BSA(Livingston) (p < 0.05). BMI was strongly associated with %BF differences
using BSA(Dubois) and BSA(Livingston) in both 2C (men: r = 0.90; women: r = 0.88)
and 5C models (r = 0.88). Though %BF(Dubois) and %BF(Livingston) were strongly
associated (r(2) = 1.000), some variability was observed on %BF differences using
BSA(Dubois) and BSA(Livingston). These findings suggest that BSA calculation is
critical in BF estimation, supporting the use of a more accurate equation for non
obese and obese subjects.
PMID- 17028413
TI - Analysis of the QT interval and its variability in healthy adults during rest and
exercise.
AB - The aim of the present study was to quantify the variability of
electrocardiographic QT and RR intervals during rest and dynamic physical
exercise, and to interpret these variabilities in terms of relative autonomic
modulation of the atrial and ventricular myocardium. We also sought to
characterize the relationships between QT, heart rate-corrected QT (QT(c)) and RR
intervals, and to consider their associations with differential autonomic
regulation. Nine males and eight females of similar age (22.8 +/- 4.7 years),
mass (75.5 +/- 13.0 kg) and aerobic fitness (43.6 +/- 7.7 ml kg(-1) min(-1))
(mean +/- SD) undertook progressive bicycle exercise. A three-lead Holter ECG was
recorded continuously during pre-exercise, exercise and recovery, and mean values
of RR, QT, QT(c), QT variability index (QTVI) and mean-normalized QT variance
(QTVN) were determined. At the onset of exercise QTVI increased rapidly compared
with rest and remained significantly elevated throughout exercise and recovery.
There were significant differences between QT(a)VI and QT(e)VI (QT measured from
Q wave onset to T wave apex (QT(a)) and T wave end (QT(e)), respectively)
throughout the experimental protocol. QTVI was significantly reduced in males
compared with females prior to exercise but was similar thereafter. We suggest
that physical exercise perturbs the resting QT-RR relationship owing to the onset
of differential parasympathetic modulation of the atrial and ventricular
myocardium. QTVI can be used to quantify the relative autonomic influence on the
atrial and ventricular myocardium during rest and exercise, and might be related
to HR-dependent and HR-independent influences on the QT interval.
PMID- 17028414
TI - Ballistocardiogram artifact removal from EEG signals using adaptive filtering of
EOG signals.
AB - We estimated ballistocardiogram (BCG) components in EEG signals recorded inside
an MRI magnet using the electro-oculogram (EOG) signals recorded simultaneously
with the EEG signals. Since the EOG signals are measured near the EEG measuring
points, it is thought that the BCG components in the EOG signals resemble the BCG
components in the EEG signals. To estimate the BCG components in the EEG signals,
we applied the Kalman filter to the EOG and EEG signals recorded inside a 3.0 T
MRI magnet. After removing the estimated BCG components from the EEG signals, we
extracted the visual-evoked potentials (VEPs) from the BCG-removed EEG signals.
To validate the efficacy of Kalman filtering in the BCG artifact removal, we have
compared three types of VEPs of eight healthy subjects: one extracted from the
raw EEG signals measured outside the magnet and the others extracted from the BCG
removed EEG signals measured inside the magnet. The BCG artifacts have been
removed with Kalman filtering as well as with the conventional BCG template
subtraction method for the sake of comparison. No significant difference in
waveforms, latencies and amplitudes has been found between the two types of VEPs
extracted from the two kinds of BCG-removed EEG signals.
PMID- 17028415
TI - Detrended fluctuation analysis of laser Doppler flowmetry time series: the effect
of extrinsic and intrinsic factors on the fractal scaling of microvascular blood
flow.
AB - The relative contribution of extrinsic (central) and intrinsic (local)
oscillatory mechanisms to the fractal scaling of blood flow in forearm cutaneous
microcirculation is unclear. The aim of this study was to investigate the
contributions of these mechanisms to the fractal properties of the blood flow
signal by using their frequency spectrum in the analyses. To evoke local
oscillatory components, acetylcholine (ACh) was iontophoresed into the forearm
and cutaneous perfusion was measured by a laser Doppler flowmeter (LDF) at rest.
Depending on the involved factors in ACh-induced vasodilatation, central, cardiac
and respiratory, signals have also increasingly appeared in LDF. The detrended
fluctuation analysis (DFA) of filtered LDF time series demonstrated that the LDF
was fractal with three distinct scaling regions. Furthermore, the findings of the
present study indicated that these regions are related to the frequency bands of
well-known control systems of blood flow and were called cardiac, cardio
respiratory and local regions. The mean scaling exponent increased with
vasodilatation in the cardiac region but decreased and even changed its sign in
the cardio-respiratory region. Inhibition of a local vasodilator mechanism not
only decreased the scaling exponent of the local region but also eliminated the
effect of respiratory coupling on fractal scaling. These findings suggest that
the scaling exponents might have a diagnostic value for detecting pathological
dynamics in vascular beds.
PMID- 17028416
TI - Isolation and characterization of rat pituitary endothelial cells.
AB - Most previous studies that determined the effect of estradiol on angiogenesis
used endothelial cells from nonpituitary sources. Because pituitary tumor tissue
receives its blood supply via portal and arterial circulation, it is important to
use pituitary-derived endothelial cells in studying pituitary angiogenesis. We
have developed a magnetic separation technique to isolate endothelial cells from
pituitary tissues and have characterized these cells in primary cultures.
Endothelial cells of the pituitary showed the existence of endothelial cell
marker, CD31, and of von Willebrand factor protein. These cells in cultures also
showed immunoreactivity of estrogen receptors alpha and beta. The angiogenic
factors, vascular endothelial growth factor and basic fibroblast growth factor,
significantly increased proliferation and migration of the pituitary-derived
endothelial cells in primary cultures. These results suggest that a magnetic
separation technique can be used for enrichment of pituitary-derived endothelial
cells for determination of cellular mechanisms governing the vascularization in
the pituitary.
PMID- 17028417
TI - Friedrich Feyrter: a precise intellect in a diffuse system.
AB - Prior to the contributions of Friedrich Feyrter (1895-1973), the regulation of
gastrointestinal function was an ill-understood field that was polarized by a
combination of the inability of clinical scientists to perceive the relationship
between the cellular elements of 'nervism' and the newly recognized chemical
messenger system. Feyrter, an Austrian pathologist of luminescent intellect and
possessed of rigorous analytic capacity, recognized the interface of the
divergent elements (neural and endocrine) and established the concept of the
diffuse neuroendocrine system. His pathological descriptions of the specialized
neuroendocrine cells producing biologically active substances and regulating
homeostasis by a network functioning via endocrine, paracrine, and neuracrine
mechanisms laid the basis for contemporary understanding of gut function. In
1938, Feyrter identified Helle Zellen (clear cells) of the pancreas and
gastrointestinal tract, which was later incorporated into the amine precursor
uptake decarboxylation concept of endocrine cells by A.G.E. Pearse (1916-2003).
Feyrter proposed a diffuse network as a functional regulatory system as opposed
to the then current doctrine of 'organ' regulation in his 1938 manuscript Uber
diffuse endokrine epitheliale Organe. In addition to this seminal contribution,
the prodigious intellect of Feyrter produced an array of novel observations
including benign and malignant tumors of the skin, gastrointestinal tract, and
eyes, carcinoid tumors and the carcinoid syndrome, the genesis of the nevus, the
transformation of lipids and disorders of cellular metabolism. Sadly, the
contributions of Feyrter were obscured in the catastrophe of wartime Germany and
his accomplishments little recognized. We describe the life and times of this
gifted scientist, teacher, and pathologist, often referred to as the 'Father of
Neuroendocrinology'.
PMID- 17028418
TI - Progestin concentrations are increased following paced mating in midbrain,
hippocampus, diencephalon, and cortex of rats in behavioral estrus, but only in
midbrain of diestrous rats.
AB - BACKGROUND: The progesterone (P(4)) metabolite, 5alpha-pregnan-3alpha-ol-20-one
(3alpha,5alpha-THP), acts in the midbrain ventral tegmental area (VTA) to
modulate the intensity and duration of lordosis. 3alpha,5alpha-THP can also have
anti-anxiety and anti-stress effects in part through actions in the hippocampus.
Separate reports indicate that manipulating 3alpha,5alpha-THP levels in the VTA
or hippocampus respectively can influence lordosis and affective behavior.
3alpha,5alpha-THP levels can also be altered by behavioral experiences, such as
mating or swim stress. Whether endogenous levels of 3alpha,5alpha-THP modulate
and/or are increased in response to affective and/or reproductively-relevant
behaviors was investigated. METHODS: In Experiment 1, rats in behavioral estrus
or diestrus were individually tested sequentially in the open field, elevated
plus maze, partner preference, social interaction, and paced mating tasks and
levels of 17beta-estradiol (E(2)), P(4), dihydroprogesterone (DHP), and
3alpha,5alpha-THP in serum, midbrain, hippocampus, diencephalon, and cortex were
examined. In Experiments 2 and 3, rats in behavioral estrus or diestrus, were
individually tested in the battery indicated above, with, or without, paced
mating and tissues were collected immediately after testing for later assessment
of endocrine measures. RESULTS: In Experiment 1, behavioral estrous, compared to
diestrous, rats demonstrated more exploratory, anti-anxiety, social, and
reproductive behaviors, and had higher levels of E(2) and progestins in serum,
midbrain, hippocampus, diencephalon, and cortex. In Experiment 2, in midbrain and
hippocampus, levels of 3alpha,5alpha-THP and its precursor DHP were increased
among rats in behavioral estrus that were mated. In diencephalon, and cortex, DHP
levels were increased by mating. In Experiment 3, in midbrain, levels of
3alpha,5alpha-THP and its precursor DHP were increased among diestrous rats that
were tested in the behavioral battery with mating as compared to those tested in
the behavioral battery without mating. CONCLUSIONS: Increased levels of
3alpha,5alpha-THP in behavioral estrus versus diestrous rats are associated with
enhanced exploratory, anti-anxiety, social, and reproductive behaviors. Rats in
behavioral estrus that are mated have further increases in 3alpha,5alpha-THP
and/or DHP levels in midbrain, hippocampus, diencephalon, and cortex than do non
mated rats in behavioral estrus, whereas diestrous rats only show 3alpha,5alpha
THP increases in midbrain in response to behavioral testing that included mating.
PMID- 17028419
TI - Prednisone blunts airway neutrophilic inflammatory response due to ozone exposure
in asthmatic subjects.
AB - BACKGROUND: The effect of corticosteroids on the ozone (O3)-induced airway
inflammation is still debated. OBJECTIVE: The aim of the study was to confirm the
effect of a short-term treatment with oral glucocorticosteroids on O3-induced
airway inflammation, detected by induced sputum analysis, and on functional
response in glucocorticosteroid-naive subjects. METHODS: A randomized, placebo
controlled study using oral prednisone (25 mg o.d. for 4 days) was carried out.
Nine mild persistent asthmatics were exposed for 2 h, on separatedays, to 0.27
ppm O3 and to air in random order, after 4 days of treatment with prednisone (25
mg o.d.) and after 4 days of placebo.Before and after exposure, pulmonary
function test was measured; 6 h afterexposure, sputum induction was done.
RESULTS: Oral glucorticosteroids did not prevent pulmonary function decrement due
to O3. After placebo, the percentage of neutrophils in induced sputum was
significantly higher after O3 than after air [52.1 (15.7-77.3) vs. 17.8 (1.7
58.4), p=0.02, O3 vs. air]. This difference was lost after 4 days of treatment
with prednisone [35.2% (10-96.2) vs. 30.9% (6.1-75.6), n.s., O3 vs. air].
Neutrophil elastase in sputum supernatant increased after O3 exposure in the
sample obtained after placebo, but not after prednisone treatment. CONCLUSIONS:
This study confirms that glucocorticosteroids reduce inflammatory airway
response, but do not prevent the airway functional impairment after O3 exposure.
PMID- 17028420
TI - Autologous serum skin test for autoantibodies is associated with airway
hyperresponsiveness in patients with asthma.
AB - BACKGROUND: Autoimmune diseases have been implicated as a cause of intrinsic
asthma; however, there is little data on the role of autoimmunity in the
pathogenesis of asthma. OBJECTIVE: The purpose of this study was to investigate
circulating functional autoantibodies against the high-affinity IgE receptor
FcepsilonRI or IgE in patients with asthma. METHODS: Twenty-eight patients with
asthma and 19 control subjects were included. All subjects were skin tested with
autologous serum to assess for the potential presence of receptor FcepsilonRI or
IgE autoantibodies. If the serum-induced wheal diameter was 1.5 mm larger than
the histamine-induced wheal diameter and that was 3 mm larger than the saline
induced wheal diameter at 30 min, the reaction was defined positive. RESULTS: Of
the 47 total subjects (both asthma patients and control subjects), 13 (27.7%) had
a positive autologous serum skin test (ASST). Of the 28 asthma patients, 8
(28.6%) were regarded as having autoimmune origin. Autoantibodies against
FcepsilonRI or IgE were found in asthma patients, irrespective of atopic status
(atopy+ 3/13 vs. atopy- 5/15). The wheal diameter related to ASST was not related
to atopy. Asthma patients with ASST-positive results as compared with patients
with ASST-negative results exhibited a significant increased airway
hyperresponsiveness (PC(20) methacholine, 2.70 +/- 1.27 vs. 9.08 +/- 2.35; p <
0.026). CONCLUSION: Our data demonstrate that aberrant autoantibodies against the
high-affinity IgE receptor FcepsilonRI or IgE are related to airway
hyperresponsiveness in patients with asthma.
PMID- 17028421
TI - Glucocorticoid regulation of GLT-1 glutamate transporter isoform expression in
the rat hippocampus.
AB - BACKGROUND: In the rat hippocampus, the predominate glutamate transporters are
GLT-1 and its recently identified isoform, GLT-1b. Chronic restraint stress
increases GLT-1b expression throughout the hippocampus while more selectively
increasing GLT-1 expression in the CA3 region. These studies suggest that GLT-1b
expression is regulated by stress levels of glucocorticoids (GCs) and GLT-1
expression is regulated by stress-induced increases in extracellular glutamate
levels in the CA3 region. METHODS: In order to differentiate between the actions
of GCs and glutamate, we examined GLT-1 isoform expression in adrenalectomized
(ADX) rats and rats exposed to stress levels of GCs. RESULTS: ADX rats revealed
no significant differences in GLT-1b mRNA or protein levels compared to sham
operated controls or ADX rats given GC replacement. However, rats exposed to
stress levels of GCs exhibited increases in GLT-1b protein expression in the CA3
region and the dentate gyrus. GLT-1 mRNA expression was increased by ADX,
increases that were inhibited by GC replacement. Similarly, stress levels of GCs
increased GLT-1 protein expression throughout the hippocampus. CONCLUSIONS: Taken
together, these data indicate that GLT-1b protein expression is regulated by
stress levels of GCs while the regulation of GLT-1 mRNA and protein expression
provides another example of the biphasic actions of GCs in the central nervous
system.
PMID- 17028422
TI - Effect of G-force on bicuspid aortic valve in aviators.
AB - BACKGROUND AND AIMS: Bicuspid aortic valve (BAV) is a common congenital cardiac
malformation. The major complications are aortic stenosis (AS), aortic
regurgitation (AR), infectious endocarditis and aortic dissection. This paper
aims to assess the hemodynamic importance of incidentally-found BAV in military
aviators and evaluate the effect of high G-force on disease progression. METHODS:
Aviators with BAV were detected by reviewing all cardiac assessment records
between 1987 and 2005. All aviators underwent annual flight surgeon examination.
Echocardiography was performed as recommended by our cardiologists and flight
surgeons. RESULTS: Eight newly diagnosed cases of BAV were found. All of the
aviators continued active aviation throughout the study period. Repeat
echocardiography demonstrated progressive widening of the aortic diameter in five
of the eight aviators. No worsening of valve dysfunction was seen in those with
mild aortic regurgitation at diagnosis. Left ventricular dimensions and function
did not deteriorate. No new valve complications, including infectious
endocarditis, were seen. The age at diagnosis strongly correlated with the root
diameter change; both total (r = 0.74, p = 0.02) and annualized (r = 0.78, p =
0.02) change. Over a mean follow-up period of 12.1 years, no difference was seen
in the progression of BAV in high-performance as compared to low-performance
aviators. CONCLUSIONS: Exposure to G-force and anti-G maneuvers does not appear
to worsen cardiac and valve function in aviators with BAV.
PMID- 17028423
TI - Inhibition of restenosis development after mechanical injury: a new field of
application for malononitrilamides?
AB - OBJECTIVE: To investigate the efficacy of the malononitrilamide FK778 to prevent
vascular smooth muscle cell (SMC) migration/proliferation, and vascular fibrosis,
the key events in restenosis development using in vivo and in vitro studies.
BACKGROUND: Since the high rate of restenosis after percutaneous transluminal
coronary angioplasty limited its long-term success, the implementation of locally
delivered antiproliferative/immunosuppressive agents became advantageous.
METHODS: Rats underwent balloon denudation of the abdominal aorta and received
sirolimus, tacrolimus, or FK778 for 28 days in varying doses. Aortas were
harvested for histologic evaluation, profibrotic gene expression, and organ
chamber studies. Antifibrotic, antiproliferative and antimigratory effects of the
immunosuppressants were further evaluated in vitro. RESULTS: Histology of
untreated animals revealed marked intimal hyperplasia with moderate luminal
obliteration. Neointima formation was dose-dependently attenuated by all three
agents with FK778 and sirolimus being most efficacious. Organ chamber relaxation
studies showed a leftward shift of the nitroglycerin and the acetylcholine dose
responses in all treatment groups, indicating diminished endothelial dysfunction.
In vivo, only FK778 treatment revealed a significant downregulation of the TGF
beta/vasorin system which could be explained by upregulation of the TGF-beta
inhibitory mediator SMAD7. In vitro, FK778 showed most potent antiproliferative
and antimigratory effects on SMC compared with sirolimus and tacrolimus. Only the
antiproliferative effect of FK778 was due to pyrimidine synthesis blockade and
could be reversed by uridine supplementation. CONCLUSIONS: The malononitrilamide
FK778 proved highly efficacious against restenosis development by targeting two
major components of intimal hyperplasia: SMC proliferation/migration and vascular
fibrosis. Thus, the introduction of malononitrilamide-loaded stents may be a
promising effort for future strategies.
PMID- 17028424
TI - Time relation between a syncopal event and documentation of atrioventricular
block in patients with bifascicular block: clinical implications.
AB - BACKGROUND: Transient high-degree atrioventricular (AV) block is a common cause
of syncope in patients with bifascicular block (BFB) but the intermittent nature
of AV block makes ECG documentation a challenge. A sensitive and safe tool to
investigate BFB patients with syncope would be a bradycardia-detecting pacemaker,
which provides a possibility of studying the time relation between the index
syncopal episode and the development of high-degree AV block. METHODS: Twenty
seven patients with BFB and syncope were studied prospectively. All patients
received a single-chamber ventricular-based pacemaker with bradycardia-detecting
ability. A bradycardia episode was defined as a heart rate of < 30 beats/min
lasting > or = 6 s. RESULTS: During a median follow-up of 60 months, a
bradycardia event was detected in 14 patients (52%), of whom 13 also had
documented high-degree AV block on ECG. The median time between the syncopal
episode and the first pacemaker-detected bradycardia event was 5 months and after
an additional median time of 6 months, high-degree AV block was documented on the
ECG. In 10 of 13 patients (77%) high-degree AV block was documented within 24
months of the syncopal episode corresponding to an annual incidence of 19% during
the first 2 years of follow-up in the study population. CONCLUSION: In this group
of BFB patients a syncopal episode was highly predictive of the development of
high-degree AV block within 24 months, justifying pacemaker therapy without prior
ECG verification.
PMID- 17028425
TI - Myelin-associated oligodendrocytic basic protein: a family of abundant CNS myelin
proteins in search of a function.
AB - The myelin-associated oligodendrocytic basic protein (MOBP) family constitutes
the third most abundant protein in CNS myelin. The mouse Mobp gene comprises
eight exons. Mobp pre-mRNA processing gives rise to at least seven Mobp splice
variants which are expressed solely in the oligodendrocyte. The predicted
proteins all, with one exception, share a 68 residue amino terminus, encoded by
exon 3. The carboxyl termini differ in length, giving rise to the diverse array
of the protein isoforms. Like myelin basic protein, MOBP is present in the major
dense line of CNS myelin suggesting a role in the compaction or stabilization of
myelin. However, Mobp homozygous null mice display no overt clinical phenotype
and no defect in the process of myelination. MOBP can induce experimental
allergic encephalomyelitis in mice and has been proposed to have a role in the
pathogenesis of multiple sclerosis. Despite 10 years of rigorous study, the
normal physiological function of MOBP remains unknown.
PMID- 17028426
TI - Activation, proliferation and commitment of endogenous stem/progenitor cells to
the oligodendrocyte lineage by TS1 in a rat model of dysmyelination.
AB - Wild-type and myelin-deficient rats received a single intraparenchymal injection
of TS1, a specific combination of IGF-1 and transferrin (Tf), into their corpus
callosum at postnatal day 4. The fate of endogenous stem cells in the brain was
examined by the expression of the stem cell marker nestin, together with Tf,
neurofilaments and glial fibrillary acidic protein from 2 to 14 days after
injection. Treated mutants lacked nestin expression in the ventricular wall and
had an increase in nestin-labeled radial cell processes in the subventricular
regions, and extended into the parenchyma. The subventricular zone was populated
by healthy new oligodendrocytes (OLs). BrdU incorporation showed that these cells
originated by proliferation and were identified as OLs based upon Tf expression.
Thus, TS1 is an effective treatment to promote endogenous subventricular zone
progenitor proliferation, migration and OL lineage specification. This strategy
offers for the first time the possibility of myelin restoration to treat myelin
disorders.
PMID- 17028427
TI - Inhibition of PC-PLC blocked the survival of mouse neural cells by up-regulating
the expression of integrin beta4 and Rb.
AB - In order to understand the survival signals of neural cells during the
development of the central nervous system (CNS), we explored the role of
phosphatidylcholine-specific phospholipase C (PC-PLC) in the survival of primary
culture mouse neural cells (MNCs). We found that when the activity of PC-PLC in
the neural cells was suppressed by its specific inhibitor, D609 (tricyclodecan-9
yl-xanthogenate), the cell survival was blocked, the viability of the cells
remarkably declined. At the same time, the expressions of integrin beta4 and Rb
protein were evidently elevated. We also examined the intracellular ROS (reactive
oxygen species) levels after the cells were treated with D609. The result showed
that the ROS level in neural cells was reduced. Our data suggested that PC-PLC
had an important role in regulating neural cell survival, and PC-PLC might
perform its function by upregulating the expressions of integrin beta4 and Rb
protein. The changes of intracellular ROS level induced by D609 indicated that a
modest level of ROS might be indispensable to neural cell survival.
PMID- 17028428
TI - The role of dopamine receptors in the neurobehavioral syndrome provoked by
activation of L-type calcium channels in rodents.
AB - In rodents, activation of L-type calcium channels with +/-BayK 8644 causes an
unusual behavioral syndrome that includes dystonia and self-biting. Prior studies
have linked both of these behaviors to dysfunction of dopaminergic transmission
in the striatum. The current studies were designed to further elucidate the
relationship between +/-BayK 8644 and dopaminergic transmission in the expression
of the behavioral syndrome. The drug does not appear to release presynaptic
dopamine stores, since microdialysis of the striatum revealed dopamine release
was unaltered by +/-BayK 8644. In addition, the behaviors were preserved or even
exaggerated in mice or rats with virtually complete dopamine depletion. On the
other hand, pretreatment of mice with D(3) or D(1/5) dopamine receptor
antagonists attenuated the behavioral effects of +/-BayK 8644, while pretreatment
with D(2) or D(4) antagonists had no effect. In D(3) receptor knockout mice, +/
BayK 8644 elicited both dystonia and self-biting, but these behaviors were less
severe than in matched controls. In D(1) receptor knockout mice, behavioral
responses to +/-BayK 8644 appeared exaggerated. These results argue that the
behavioral effects of +/-BayK 8644 are not mediated by a presynaptic influence.
Instead, the behaviors appear to result from a postsynaptic activation of the
drug, which does not require but can be modified by D(3) or D(1/5) receptors.
PMID- 17028429
TI - Characterization of mouse striatal precursor cell lines expressing functional
dopamine receptors.
AB - Dopamine and its receptors appear in the developing brain early in the embryonic
period and dopamine receptor activation influences proliferation and
differentiation of neuroepithelial precursor cells. Since dopamine D(1) and D(2)
receptor activation produces opposing effects on precursor cell activity,
dopamine's overall effects may correlate with relative numbers and activity of
each receptor subtype on the precursor cells. Dopamine receptor expression and
activity in individual precursor cells in the intact brain are difficult to
ascertain. Therefore, cell lines with known receptor expression profiles can be
useful tools to study dopamine's influence on neuroepithelial cells. We report
characterization of dopamine receptor expression and activity profiles in three
mouse striatal precursor cell lines and suggest that these cell lines can be
valuable tools to study dopamine's effects on striatal precursor cell
proliferation and differentiation.
PMID- 17028430
TI - Differentiated dopaminergic MN9D cells only partially recapitulate the
electrophysiological properties of midbrain dopaminergic neurons.
AB - The cell line MN9D, a fusion of embryonic ventral mesencephalic and neuroblastoma
cells, is extensively used as a model of dopamine (DA) neurons because it
expresses tyrosine hydroxylase and synthesizes and releases DA. These cells are
also used to test mechanisms and potential therapeutics relevant to the loss of
DA neurons in Parkinson's disease. To date, little work has been done to
determine whether MN9D cells electrophysiologically resemble mature DA neurons.
We examined sodium, calcium and potassium currents in undifferentiated and
differentiated MN9D cells, and compared these to those found in acutely
dissociated mouse substantia nigra pars compacta DA neurons. It was observed that
undifferentiated MN9D cells bore no resemblance to DA neurons. Upon
differentiation with butyric acid with or without a prior treatment with glial
cell line-derived neurotrophic factor, differentiated MN9D cells produce an
electrophysiological profile that more closely resembles substantia nigra pars
compacta DA neurons even though the A-type potassium current remains noticeably
absent. These observations demonstrate that undifferentiated MN9D cells are not
reasonable models of DA neurons. Although differentiated MN9D cells are closer to
the mature DA neuronal phenotype, they do not fully mimic DA neurons and are
likely to be of questionable value as a model because of their substantive
differences, including the lack of the characteristic A-type potassium current.
The future use of one or a combination of growth or other factors to
differentiate MN9D cells may yield a more useful model system for Parkinson's
disease studies in vitro.
PMID- 17028431
TI - Distinct but overlapping functions for the closely related p190 RhoGAPs in neural
development.
AB - The p190 RhoGAPs, p190A and p190B, are highly related GTPase-activating proteins
for the Rho GTPases. Rho GTPases and p190A reportedly control various aspects of
brain development, and we hypothesized that p190B would be likewise involved in
neuronal development. We find that like p190A, p190B is prominently expressed in
the developing and adult brain. Unlike p190A, p190B is not abundantly tyrosine
phosphorylated. We further demonstrate, using p190B-deficient mice, that p190B is
required for normal brain development. Mice lacking p190B display several major
defects, including (1) deficits in the formation of major forebrain commissures,
including the corpus callosum and anterior commissure, (2) dilation of the
lateral ventricles, suggesting inhibition of neurogenesis and/or survival, (3)
thinning of the neocortical intermediate zone, suggesting defects in neuronal
differentiation and/or axonal outgrowth, and (4) impaired neuronal
differentiation. These defects are similar to, but distinct from, those described
in p190A-deficient mice. RNA interference-mediated knockdown of neither p190
protein results in significant inhibition of neurite outgrowth in neuroblastoma
cells, despite an apparent increase in RhoA activity. We conclude that p190
RhoGAPs control pivotal aspects of neural development, including neuronal
differentiation and process outgrowth, and that these effects are mediated by
signaling systems that include, but are not limited to, RhoA.
PMID- 17028432
TI - Euglycemic hyperinsulinemia in severe sepsis and septic shock.
AB - BACKGROUND: Recent studies have suggested that strict glucose control with
intensive insulin therapy in critically ill patients may result in better
outcomes. Whether this is also true in septic shock has not been determined. In
addition, whether it is the insulin administration per se or the glucose control
that contributes to the beneficial effects is unclear. We raised the hypothesis
that euglycemic hyperinsulinemia (EH) might improve the outcome from septic shock
due to peritonitis. MATERIALS AND METHODS: Fourteen anesthetized, mechanically
ventilated, and hemodynamically monitored sheep received 1.5 g/kg body weight
i.p. feces to induce sepsis. Ringer's lactate and 6% hydroxyethyl starch
solutions were infused throughout the experiment to prevent hypovolemia. Two
hours after feces injection, the animals were randomized to either an EH group (n
= 7) receiving insulin 0.25 U/ kg/h, 20% glucose (to maintain blood glucose at 40
90 mg/dl), and potassium (to maintain the potassium level at 4.0- 5.5 mmol/l) or
a control group (n = 7) with no intervention. All animals were studied until
their spontaneous death or for 30 h. RESULTS: The EH group received a greater
volume of 20% glucose, but blood glucose and potassium concentrations were
similar in the two groups. No significant differences were found in hemodynamic
variables. The circulating interleukin-6 levels increased in both groups after
feces injection, but tended to be lower in the EH group (p < 0.05). The survival
times were similar in the two groups (median 20.0 h in the EH group vs. 17.0 h in
the control group; p = 0.73). CONCLUSIONS: In this clinically relevant sheep
septic shock model, EH decreased blood interleukin-6 concentrations but did not
change hemodynamics or improve the outcome.
PMID- 17028433
TI - Different protection mechanisms after pretreatment with glycine or alpha-lipoic
acid in a rat model of warm hepatic ischemia.
AB - BACKGROUND/AIM: Alpha-lipoic (LA) acid pretreatment has previously been described
to reduce ischemia/reperfusion injury (IRI) after warm liver ischemia, whereas
glycine pretreatment has been shown to be protective mostly in models of cold
hepatic ischemia. The aim of this study was to determine whether glycine
decreases IRI after warm hepatic ischemia. Furthermore we investigated whether
doses of LA other than those used previously are also protective against IRI
after warm hepatic ischemia. METHODS: Selective liver ischemia was maintained
over a period of 90 min. In long-term as well as short-term experiments we
studied IRI in several groups comparing animal survival as the pivotal endpoint.
RESULTS: Animal survival was improved by glycine and 5,000 micromol LA, whereas
all animals died within 3 days after pretreatment with 50 micromol LA. In the
glycine group we observed a tendency towards decreased apoptosis-related cell
death measured by the activity of caspase-3 in liver tissue and the percentage of
TUNEL-positive hepatocytes in comparison to the untreated group. Serum alpha
glutathione S-transferase, lipid peroxidation, and caspase-3 activity as well as
the percentage of TUNEL-positive hepatocytes and the percentage of liver necrosis
were only significantly decreased by 5,000 micromol LA pretreatment. Liver tissue
levels of tumor necrosis factor (TNF)alpha were reduced only in the glycine group
whereas TNFalpha was increased in the untreated as well as the LA group. Levels
of TNFalpha mRNA were upregulated in both the glycine- and LA-pretreated groups.
CONCLUSION: Our data show that increased animal survival by glycine was
accompanied by a reduced TNFalpha content in liver tissue. Protection by glycine
is likely to result from a reduction in adverse TNFalpha effects. Administration
of high-dose LA on the other hand led to a significant reduction in necrosis- and
apoptosis-related cell death in IRI of the liver without a reduction in liver
TNFalpha.
PMID- 17028435
TI - Evaluation of the risk factors for short-term mortality after acute ischemic
stroke in the elderly: is there a role for nutritional risk assessment?
PMID- 17028434
TI - Effective antitumoral immune responses are not induced by cytosine deaminase
suicide gene transfer in a syngeneic rat pancreatic carcinoma model.
AB - BACKGROUND: Experimental gene transfer can make tumors more immunogenic, leading
to local regression and inducing immunological memory sufficient to permit
resistance to a tumor rechallenge. However, this rarely had any significant
impact on large established tumors. METHODS: To analyze potential immunological
effects, we used weakly immunogenic pancreatic carcinomas in syngeneic,
immunocompetent Lewis rats and performed in situ adenoviral mediated cytosine
deaminase (CD) gene transfer followed by administration of the prodrug, 5
fluorocytosine (5FC). In order to reflect the clinical situation, such treated
tumors were surgically resected and animals were rechallenged with parental DSL6A
pancreatic tumor cells. Tumor growth and cytotoxic activity of immune cells were
determined. RESULTS: CD/5FC treatment of the DSL6A cells revealed significant
induction of apoptosis in vitro and slowed down tumor progression in syngeneic
hosts. Furthermore, we observed neither significant change in tumor growth nor
protective immunity in the rechallenged animals. Analysis of T lymphocytes showed
no specific cytotoxic activity against DSL6A cells. There was only a trend
towards a minor NK cell activation. CONCLUSIONS: Albeit the present study failed
to induce protective antitumor immunity, the initial finding of reduced tumor
growth argues for the development of multimodal therapeutic options to overcome
negative impacts of advanced malignant disease or chemotherapy-related anergy and
immunosuppression.
PMID- 17028437
TI - Nuclear factor-kappab (NF-kappaB): an unsuspected major culprit in the
pathogenesis of endometriosis that is still at large?
AB - Endometriosis, defined as the ectopic presence of endometrial glandular and
stromal cells outside the uterine cavity, is a common benign gynecological
disorder with an enigmatic pathogenesis. Many genes and gene products have been
reported to be altered in endometriosis, yet some of them may not be major
culprits but merely unwitting accomplices or even innocent bystanders. Therefore,
the identification and apprehension of major culprits in the pathogenesis of
endometriosis are crucial to the understanding of the pathogenesis and would help
to develop better therapeutics for endometriosis. Although so far NF-kappaB only
has left few traces of incriminating fingerprints, several lines of investigation
suggest that NF-kappaB, a pivotal pro-inflammatory transcription factor, could
promote and maintain endometriosis. Various inflammatory agents, growth factors,
and oxidative stress activate NF-kappaB. NF-kappaB proteins themselves and
proteins regulated by them have been linked to cellular transformation,
proliferation, apoptosis, angiogenesis, and invasion. Interestingly, all existing
and nearly all investigational medications for endometriosis appear to act
through suppression of NF-kappaB activation. In endometriotic cells, NF-kappaB
appears to be constitutively activated, and suppression of NF-kappaB activity by
NF-kappaB inhibitors or proteasome inhibitors suppresses proliferation in vitro.
Viewing NF-kappaB as a major culprit, an autoregulatory loop model can be
postulated, which is consistent with existing data and, more importantly, can
explain several puzzling phenomena that are otherwise difficult to interpret
based on prevailing theories. This view has immediate and important implications
for novel ways to treat endometriosis. Further research is warranted to precisely
delineate the roles of NF-kappaB in the pathogenesis of endometriosis and to
indict and convict its aiders and abettors.
PMID- 17028436
TI - The obstetrical history in patients with Pfannenstiel scar endometriomas--an
analysis of 81 patients.
AB - INTRODUCTION: The participation of immune tolerance during pregnancy was
suggested to be an important factor predisposing to the implantation of decidual
cells after cesarean section in Pfannenstiel scar. Delivery at term is related to
the termination of immune tolerance to fetal antigens that is maintained
throughout pregnancy. Substantial proportion of cesarean section deliveries is
performed before the onset of true term labor. The aim of this study was to
analyze the clinical symptoms of spontaneous beginning of labor in pregnant women
in whom cesarean sections were performed and in whom Pfannenstiel scar
endometriomas were observed during follow-up. MATERIALS AND METHODS: We have
retrospectively analyzed 81 patients following the surgical removal of scar
endometrioma after cesarean section. Obstetrical histories of cesarean sections
in the number of 5,370 preceding the occurrence of the scar endometrioma were
analyzed. These data were collected in six different Gynecological and
Obstetrical wards in Malopolska Province in Poland. Analysis of data was started
by the retrospective evaluation of regular uterine contractions, uterine cervix
ripening before cesarean section and the indications for surgery. RESULTS: In 67
women from the group of 81 patients cesarean sections were performed with unripe
uterine cervix and without the presence of regular uterine contractions. Elective
indications for cesarean sections were predominant in this group of women. The
relative risk of scar endometriomas occurrence following cesarean sections
performed before onset of labor in comparison to cesarean sections following
spontaneous onset of labor was statistically significantly higher [RR = 2.16, 95%
CI = 1.21-3.83; OR = 2.18, 95% CI = 1.22-3.89]. CONCLUSIONS: Cesarean section
performed before spontaneous onset of labor may increase substantially the risk
of occurrence of scar endometriomas.
PMID- 17028438
TI - Direct protection by a gonadotropin-releasing hormone analog from doxorubicin
induced granulosa cell damage.
AB - BACKGROUND/AIMS: Recent clinical applications suggest a beneficial effect of
gonadotropin-releasing hormone analog (GnRHa) as a gonadal protector from
chemotherapy-induced premature ovarian failure. This study aimed to determine
cellular mechanisms involved in the protective action of GnRHa against granulosa
cell damage caused by doxorubicin. METHODS: Granulosa cells were obtained by
ultrasound-guided follicular aspiration from patients undergoing in vitro
fertilization, and screened for GnRH receptor expression prior to analyses. The
cellular function was assessed by measuring the conversion of exogenously
supplied androstenedione to estradiol-beta (E2) in response to follicle
stimulating hormone (FSH) (1 microM). RESULTS: Exposing to doxorubicin for 12 h
before FSH stimulation caused a concentration-dependent inhibition of the E2
secretion to a minimum level of 20% of control. When the cells were incubated
with a GnRHa for 12 h before and during exposure to doxorubicin, granulosa cells
produced an equal level of E2 to that of control cells. The protective action of
GnRHa was dose-dependent; a half-maximal effect occurred at 10 nM. Preincubation
with GnRHa alone had no effect on FSH-induced E2 production. CONCLUSION: These
findings demonstrate that a GnRHa may retard doxorubicin-induced granulosa cell
damage, suggesting an additional GnRH activity to protect the gonads during
chemotherapy through GnRH receptor-mediated mechanism(s).
PMID- 17028439
TI - Hypoglycaemia-insulin test: discordant growth hormone and cortisol response in
paediatric patients regarding recovery from hypoglycaemia with or without oral
glucose solution.
AB - BACKGROUND: Hypoglycaemia-insulin test (HIT) is the 'gold standard' for the
diagnosis of adrenal-pituitary-hypothalamic axis disorders. Controversy exists on
the convenience of recovery from an insulin-induced hypoglycaemia since this test
is not risk-free. OBJECTIVE: To ascertain whether recovery from insulin-induced
hypoglycaemia with an oral glucose solution produces a different response of
growth hormone (GH) and cortisol at different times of the study compared with
spontaneous recovery from hypoglycaemia. PATIENTS AND METHODS: Prospective study
of 100 children and adolescents with growth delay who underwent an HIT. Patients
were consecutively assigned to two groups of 50. In one group recovery from
hypoglycaemia occurred spontaneously and in the other recovery was achieved with
an oral glucose solution (20 g of glucose) when glycaemia was under 30 mg/dl. The
two groups did not differ in age, sex, pubertal status, weight, height and IGF-I
levels. RESULTS: The response of GH at 30, 60, 90 and 120 min and cortisol at 10,
60, 90 and 120 min was lower and statistically significant in patients with
recovery from hypoglycaemia with oral glucose solution. GH deficiency was
diagnosed more frequently in patients recovered with glucose solutions (94%)
compared to those with spontaneous recovery (68%). CONCLUSIONS: Oral glucose
solution administration when glycaemia was under 30 mg/dl in HIT produced a lower
GH and cortisol response to insulin stimulus and a greater frequency of GH
deficit diagnosis.
PMID- 17028441
TI - Deterioration of visual acuity associated with growth hormone therapy in a child
with extreme short stature and high hypermetropia.
AB - BACKGROUND: Growth hormone (GH) has long been implicated in the pathogenesis of
diabetic retinopathy, although its precise role remains ill-defined. In 1998, an
association between exogenous human GH and retinal pathology in non-diabetic
subjects was described. CASE REPORT: A female child with extreme short stature of
unknown aetiology (height -7.38 SD at 11.3 years) and severe hypermetropia
developed retinopathy with visual deterioration during two separate empiric
trials of GH therapy. On the first occasion, a relatively high dose of GH (10.5
mg/m2/week) administered from age 4.4 to age 4.7 years was associated with the
development of central serous retinopathy, resulting in marked reduction in
visual acuity. On cessation of GH, the macular oedema resolved, and visual acuity
improved. At age 5.6 years, GH therapy was re-introduced at a lower dose (3.9
mg/m2/week) and her vision monitored closely. Bilateral retinal oedema recurred
after 3 months, and GH therapy was stopped. Once again, the macular oedema
regressed, and visual acuity improved following withdrawal of GH. These
ophthalmic changes contra-indicated further GH therapy. CONCLUSION: We suggest
that GH may be a risk factor in the development of retinopathy in certain non
diabetic patients, especially in the presence of a severe refractive error.
PMID- 17028440
TI - Unique deletion in exon 5 of SHOX gene in a patient with idiopathic short
stature.
AB - BACKGROUND/AIM: It is known that haploinsufficiency for the SHOX gene (short
stature homeobox gene on the X chromosome) is responsible for short stature in
Turner syndrome and Leri-Weill dyschondrogenesis, and it has been reported that
it is responsible for upwards of 1 in 50 cases of idiopathic short stature. SHOX
haploinsufficiency is also associated with various radiographic abnormalities,
such as coarse trabecular pattern, short metacarpals/metatarsals with metaphyseal
flaring, altered osseous alignment at the wrist, radial/tibial bowing,
triangularization of the radial head, abnormal tuberosity of the humerus, and an
abnormal femoral neck. Shortening and bowing of the radius and dorsal dislocation
of the distal ulna characterize the Madelung deformity. These characteristic
findings led us to do a study assessing the predictive value of certain
radiographic features in association with genetic markers of idiopathic short
stature. METHODS: Here we describe a case of a Hispanic male with idiopathic
short stature and Madelung deformity with a novel mutation in the SHOX gene.
RESULTS: Additional studies revealed a strong family history of short stature and
the same SHOX mutation segregating from the mother. CONCLUSION: This case
resulted in the description of a novel mutation in exon 5 (M202delA) and suggests
the importance of screening for SHOX mutations in patients with idiopathic short
stature with subtle radiographic abnormalities, including the components of the
Madelung deformity in their bone age films.
PMID- 17028442
TI - Mutation and polymorphism analyses of INSL3 and LGR8/GREAT in 62 Japanese
patients with cryptorchidism.
AB - BACKGROUND/AIMS: Although insulin-like factor 3 (INSL3) and its receptor leucine
rich repeat-containing G protein-coupled receptor 8/G protein-coupled receptor
affecting testis descent (LGR8/GREAT) are essential for the gubernacular
development, mutations of INSL3 and LGR8/GREAT are infrequent in patients with
cryptorchidism (CO), and there is no report documenting a positive association of
CO with a polymorphism in INSL3 or LGR8/GREAT. Here, we further examined the
relevance of INSL3 and LGR8/GREAT mutations and polymorphisms to the development
of CO. METHODS: Sixty-two Japanese CO patients and 60 fertile males were studied.
INSL3 was analyzed by direct sequencing and restriction enzyme digestion, and
LGR8/GREAT was examined by denaturing high-performance liquid chromatography
followed by direct sequencing for exons with abnormal chromatogram patterns.
RESULTS: No definitive mutation was identified in both genes. Six polymorphisms
were detected in INSL3 or LGR8/GREAT and Thr/Thr genotype of Ala60Thr
polymorphism in INSL3 was strongly associated with CO (p=0.0024, odds ratio=5.3,
95% confidence interval=1.7-17). CONCLUSION: The results, in conjunction with the
previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and
that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a
susceptibility factor for the development of CO.
PMID- 17028443
TI - The quail mesonephros: a new model for renal senescence?
AB - BACKGROUND/AIMS: Renal senescence during normal aging is associated with specific
vascular alterations and tissue degeneration. Although the degenerative program
executed during embryonic kidney development is known to include vascular
alterations, studies yet have to examine whether it involves replicative
senescence. In this study, we assessed the potential of the quail mesonephros, a
transitory embryonic kidney, as a model of human renal senescence. METHODS: Quail
embryos with developing or degenerating mesonephros were studied on day 6 or day
11 of incubation, respectively. Senescence-associated beta-galactosidase
activity, a marker of replicative senescence, was examined on whole mounts and
sections. Senescent vascular characterization was performed by the scanning
electron-microscopic analysis of vascular corrosion casts. RESULTS: Senescence
associated beta-galactosidase activity was found only in old mesonephros.
Moreover, at 11 days of incubation glomerular capillaries showed discontinuities
and were thinner and more tortuous than those observed at 6 days, characteristics
also reported for the aging human kidney. CONCLUSION: The degenerating quail
mesonephros is a potential model of renal senescence, showing biochemical and
morphological characteristics of the aging human kidney.
PMID- 17028444
TI - Altered expression of matrix-related molecules in the development of chronic
Thy1.1 nephritis.
AB - BACKGROUND/AIM: Matrix production and degradation are critically important in
chronic nephritis. Our aim was to investigate the precise expression of matrix
related molecules which is essential for understanding the pathogenesis of renal
disease. METHODS: Chronic nephritis was induced by a single injection of anti
Thy1.1 antibody to unilaterally nephrectomized rats. RNA was extracted from renal
cortex and isolated glomeruli 4, 7, and 10 weeks after the antibody injection.
Matrix-related gene expressions were measured by polymerase chain reaction. The
expression of alpha1(IV) and alpha3(IV) collagens was studied by
immunohistochemistry. The gelatinolytic activity in the glomeruli was assayed by
gelatin zymography. RESULTS: Polymerase chain reaction revealed an increase of
alpha1(IV) in both glomeruli and renal cortex from nephritic rats. In contrast,
the expression of alpha3(IV), normally a component of the glomerular basement
membrane, was decreased in nephritic animals. Immunohistochemistry confirmed the
finding that alpha1(IV) and alpha3(IV) were up- and downregulated, respectively,
in the glomeruli. Gene expression and activity of matrix metalloproteinase 2 were
enhanced, while those of matrix metalloproteinase 9 were clearly suppressed in
nephritis. CONCLUSIONS: Downregulation of alpha3(IV) and enhancement of the
matrix metalloproteinase-2 activity in the glomeruli may contribute to the
glomerular damage by altering the glomerular basement membrane components.
Impairment of the glomerular basement membrane integrity may possibly be
implicated in irreversible renal dysfunction.
PMID- 17028445
TI - Serum ghrelin and cholesterol values in suicide attempters.
AB - In our previous study, we demonstrated that suicide attempters had statistically
significant lower leptin and cholesterol levels compared with healthy controls.
In keeping with our previous report regarding lower serum cholesterol and leptin
levels in suicide attempters compared with healthy controls, the relationship
between cholesterol and leptin, and ghrelin, we aimed to evaluate serum total
cholesterol and ghrelin levels in suicide attempters. In the present study, 30
patients with suicide attempts (aged 18-47 years) and the same number of healthy
controls were compared with regard to serum total cholesterol and ghrelin levels.
The mean cholesterol level of the patients was significantly lower than that of
the controls. On the other hand, the suicide attempters had significantly higher
ghrelin levels compared with the controls. The results suggest that suicide
attempts seem to be associated with decreased serum cholesterol and higher
ghrelin values.
PMID- 17028447
TI - Nitric oxide and neopterin in bipolar affective disorder.
AB - BACKGROUND: There is an increasing interest in the role of nitric oxide (NO) and
pterines in the pathophysiology of neuropsychiatric disorders. The results so far
show an inconsistent pattern. METHODS: In the present study, neopterin and a
measure of NO synthesis in plasma of symptomatic and euthymic bipolar affective
patients were compared to those of patients with a major depression and healthy
controls. As an index of NO synthesis, the ratio of the amino acids citrulline
and arginine (Cit-Arg ratio) was calculated. Neopterin is a bypass product in the
synthesis of tetrahydrobiopterin, which is a cofactor of NO synthase. RESULTS:
The results indicate that both neopterin and the Cit-Arg ratio are decreased in
bipolar affective patients, irrespective of their symptomatic status. In
addition, an association between the values of the Cit-Arg ratio and the
neopterin level was observed, which is suggestive for a low tetrahydrobiopterin
activity. CONCLUSION: NO formation may be endangered in bipolar affective
disorder.
PMID- 17028446
TI - Constitutional downregulation of SEMA5A expression in autism.
AB - There is strong evidence for the importance of genetic factors in idiopathic
autism. The results from independent twin and family studies suggest that the
disorder is caused by the action of several genes, possibly acting epistatically.
We have used cDNA microarray technology for the identification of constitutional
changes in the gene expression profile associated with idiopathic autism. Samples
were obtained and analyzed from 6 affected subjects belonging to multiplex autism
families and from 6 healthy controls. We assessed the expression levels for
approximately 7,700 genes by cDNA microarrays using mRNA derived from Epstein
Barr virus-transformed B lymphocytes. The microarray data were analyzed in order
to identify up- or downregulation of specific genes. A common pattern with nine
downregulated genes was identified among samples derived from individuals with
autism when compared to controls. Four of these nine genes encode proteins
involved in biological processes associated with brain function or the immune
system, and are consequently considered as candidates for genes associated with
autism. Quantitative real-time PCR confirms the downregulation of the gene
encoding SEMA5A, a protein involved in axonal guidance. Epstein-Barr virus should
be considered as a possible source for altered expression, but our consistent
results make us suggest SEMA5A as a candidate gene in the etiology of idiopathic
autism.
PMID- 17028448
TI - The serotonin transporter gene: polymorphism and haplotype analysis in Russian
suicide attempters.
AB - The focus on gender-specific genes associated with female suicide is justified by
the possible dimorphic nature of the serotonergic system and by the greater
number of suicide attempts in females. We performed analysis of the promoter (5
HTTLPR) and intron 2 (STin2 VNTR) polymorphisms and haplotypes of the serotonin
transporter gene in Russian suicide attempters, separately in men and women. Our
findings indicate the contribution of the SLC6A4 gene to susceptibility for
suicidal behavior in women, but not in men. The L/L genotype (p = 0.013, OR =
2.09) and L10 haplotype (p = 0.04, OR = 1.77) were associated with suicide in
Russian women only. Further investigations of this gene in different phenotypic
groups are necessary.
PMID- 17028449
TI - Association of eating disorders with catechol-o-methyltransferase gene functional
polymorphism.
AB - AIM: The aim of this study was to evaluate functional catechol-O
methyltransferase (COMT) genetic variation as a risk factor for eating disorders
(ED). METHOD: Eighty women receiving treatment for serious ED (52 for anorexia
nervosa, 28 for bulimia nervosa) and 116 age-matched females in the control group
underwent COMT genotyping for polymorphism in exon 4 (codon 158). Both the low
activity allele and the high-activity allele (H) were determined. RESULTS: The
H/H genotype was twice as frequent in the ED group as in the control group (52.5%
in the ED group and 25% in controls, chi(2) = 15.5, d.f. = 2, p < 0.001, odds
ratio = 3.343). The H/H genotype was found in 57.7% of anorexia nervosa patients
(chi(2) = 16.860, p < 0.001, Hardy-Weinberg equilibrium = 0.003, odds ratio =
4.202). The H allele (val) was discovered in 66.9% of ED patients in comparison
to 47.8% of patients from the control group (chi(2) = 13.89, p < 0.001, odds
ratio = 6.088). In the anorexia group, H allele frequency was enhanced even
higher (70.2 vs. 47.8%, chi(2) = 14.48, p < 0.001, odds ratio = 8.175). The
genotype associations in the subgroup of bulimia patients were not significant,
but a trend for a higher frequency of the H allele was found (p = 0.084, odds
ratio = 5.309). CONCLUSIONS: These findings seem to suggest that a turnover of
catecholamines, connected with polymorphism determining high activity of COMT
enzyme, is connected with the risk of ED occurrence, particularly anorexia
nervosa. The risk is significantly higher for women with an allele of higher
activity.
PMID- 17028450
TI - Assessment of cancer-related pain.
PMID- 17028451
TI - The burden of pain of inpatients undergoing radiotherapy--discrepancies in the
ratings of physicians and nurses.
AB - BACKGROUND: The aim of this study was to rate the burden of pain of cancer
patients receiving radiotherapy from the point of view of the patients themselves
as well as the physicians and nurses caring for the patient, and to examine
possible differences in the ratings. PATIENTS AND METHODS: 68 cancer patients
received a pain questionnaire about pain intensity and subjective well-being. At
the same time, physicians and nurses answered 7 pain-related questions about each
patient. RESULTS: 34% of the patients reported strong or very strong pain in the
past week, 8% even unbearable pain. 66% felt psychologically distressed, 70%
developed anxiety because of pain. 74% believed that pain is an essential part of
the disease. Nurses and physicians often underestimate patients' burden of pain.
Nevertheless, the rating of the nurses is more accurate than that of the
physicians. CONCLUSION: Physicians and nurses often underestimate pain intensity.
It seems that several patients are unable or unwilling to express their pain or
that therapists lack adequate methods of pain assessment. To optimize pain
treatment, communication between patients, physicians and nurses needs to be
improved.
PMID- 17028452
TI - Retrospective analysis of CD38 expression in 102 patients with B-CLL with a
maximum follow-up of 18 years: incidence and prognostic significance.
AB - BACKGROUND: The aim of this study was to evaluate the incidence of CD38
expression in all CLL patients of our institution and to determine its prognostic
significance in correlation with other parameters of the disease. PATIENTS AND
METHODS: We analyzed the CD38 expression in 102 B-CLL patients referred to our
department over a period of 12 months. RESULTS: The follow-up period ranged from
0 to 18 years. 30 patients (29%) were CD38-positive (CD38+) and 72 patients (71%)
were CD38-negative (CD38-) with a median age of 65 and 64 years, respectively. Of
the Binet A patients (77), 25% showed an expression of CD38; in Binet B/C
patients (25), 67% expressed CD38. Median survival of the CD38- group was 77.5
months and of the CD38+ group 56.3 months. CD38 expression was associated with
shorter lymphocyte doubling time (p < 0.0001), a more advanced stage of the
disease, and a shorter therapy- and progression-free time (p < 0.0017/p <
0.0012), which was also true in the Binet A subgroup. In 2 cases, we detected a
shift from the CD38- to the CD38+ phenotype. CONCLUSION: We found a low incidence
of CD38+ CLL patients, and CD38 expression predicted significantly a more
advanced stage of the disease, shorter lymphocyte doubling time and shorter
therapy- and progression-free time.
PMID- 17028453
TI - PAC fixed dose: pharmacokinetics of a 1-hour paclitaxel infusion and comparison
to BSA-normalized drug dosing.
AB - BACKGROUND: The aim of this study was to determine the pharmacokinetics (PKs) of
a 175-mg fixed dose of paclitaxel (PAC) after a 1-h infusion in cancer patients
and to compare them with the PK parameters from a study with a dose normalized to
the body surface area (BSA) (100 mg/m2). PATIENTS AND METHODS: PAC PKs were
studied during the first course of therapy in 13 patients. A fixed dose of 175 mg
PAC was administered weekly by a 1-h infusion to patients with advanced cancer.
Total PAC in serum was quantified by high-performance liquid chromatography
(HPLC). PK parameters were calculated by non-compartmental and model-dependent
methods. RESULTS: The mean BSA of 12 patients (1 patient excluded from all
analyses because of prolonged infusion duration) was 1.79 m2 (coefficient of
variation (CV) 7.8%), the mean dose referred to the individual BSAs was 98.3
mg/m2 (CV 8.3%). The mean area under the curve (AUC) was 6,193 ng/ml x h (CV
46%), the mean plasma clearance (Clp) was 19.7 l/h/m2 (CV 45%), and the volume of
distribution at steady state (Vss) was 121.6 l/m2 (CV 52%). The mean residence
time (MRT) was 7.6 h (CV 46%), the mean distribution half-life (t1/2 alpha) of
PAC(tot) was 0.4 h (CV 62%), and the elimination half-life (t1/2 beta) 10.0 h (CV
42%). Maximum plasma concentration Cmax was 3,161 ng/ml (CV 36%). The mean time
above 0.05 microM (42.7 ng/ml) was 19.7 h, and the mean time above 0.1 microM
(85.4 ng/ml) was 10.6 h. CONCLUSIONS: In this study, a fixed dose of PAC of 175
mg corresponds to a mean BSA-normalized dose of 98.3 mg/m2 (range 88.8-117.4
mg/m2). A higher variability of PK parameters was observed compared to previously
published results of a PK study with BSA-normalized dosing of 100 mg/m2. However,
the AUC and the time above threshold concentrations did not depend on the dose.
Therefore, a fixed dose of 175 mg weekly could be an option for palliative
treatment with PAC and may offer a simple but effective schedule for PAC
treatment.
PMID- 17028454
TI - Primary central nervous system lymphoma in an Asian population: a 15-year
experience.
AB - BACKGROUND: The aim of this study was to characterize primary central nervous
system lymphoma (PCNSL) among Asian patients and to determine their outcomes with
different therapeutic modalities. PATIENTS AND METHODS: Between 1990 and 2005, 37
patients with PCNSL were analyzed within 5 different treatment groups:
radiotherapy alone (arm A), combined chemoradiation (arm B), chemotherapy alone
with methotrexate (MTX) > or = 1 g/m2 (arm C), miscellaneous therapy (arm D), and
best supportive care (arm E). RESULTS: The median age at presentation was 59
years, and the majority of patients were male (68%). All patients had aggressive
diffuse large B-cell lymphoma. The number of patients in arms A to E were 6, 16,
3, 8 and 4, respectively. The overall median survival was 7.4 months, 54.1
months, not reached, 8.9 months and 0.9 months, respectively. Use of MTX 1-2.5
g/m2 per cycle and an ECOG performance status of 0-2 were each associated with
improved survival on univariate analysis (p = 0.022 and p = 0.049, respectively).
Compared to radiotherapy alone, use of combined chemo-radiation was associated
with a trend towards improved overall median survival (7.4 vs. 54.1 months, p =
0.058). CONCLUSION: The clinical characteristics and treatment outcomes in our
Asian patients were comparable to those reported in Western series. Use of MTX 1
2.5 g/m2 per cycle and an ECOG performance status of 0-2 were associated with
improved survival.
PMID- 17028455
TI - Verrucous carcinoma of the temporal bone and maxillary antrum: two unusual
presentations of a rare tumor.
AB - BACKGROUND: Verrucous carcinoma (VC) is a low-grade variant of squamous cell
carcinoma. The involvement of the temporal bone and maxillary antrum is very
rare. PATIENTS AND METHODS: The clinicopathologic features of 2 such tumors are
reported, and the pertinent literature is reviewed. RESULTS: In the 2 patients,
the diagnostic procedure was complicated due to initial inconclusive histology.
Both were treated with concomitant radiochemotherapy. They were free of disease
for 5.8 and 11 years after diagnosis. An additional 15 cases of VC of the
temporal bone and 10 cases of maxillary antrum tumors have been reported in the
literature. In 10 patients, multiple biopsies were required, and in 7 patients, a
definitive histological diagnosis was not obtained before surgery. The disease
reappeared in 8 out of 15 patients treated solely with surgery. Only 2 of them
were salvaged by reoperation. Radiochemotherapy only (without any surgery) was
successfully used in 4 patients. CONCLUSIONS: VC of the temporal bone or
maxillary antrum is an extremely rare tumor. For reliable histological diagnosis,
multiple biopsies of deep and ample tissue samples are mandatory. Surgery is a
mainstay of therapy; however, radiochemotherapy also represents a viable
treatment option with curative potential.
PMID- 17028456
TI - Leukocytoclastic vasculitis and acute renal failure after influenza vaccination
in an elderly patient with myelodysplastic syndrome.
AB - BACKGROUND: Influenza vaccination is recommended for individuals over 65 years of
age and for all patients with chronic diseases who are at risk. Side effects
which are seen in 1-10% of the vaccinated individuals are usually mild and
consist of local reactions and constitutional symptoms. Since 1974, about 30
cases of vasculitis following influenza vaccination have been reported. CASE
REPORT: We here describe a 70-year-old male patient with a 5-year history of
myelodysplastic syndrome, who had received continuous steroid treatment since
2004 and presented with leukocytoclastic vasculitis and acute renal failure
requiring hemodialysis therapy 1 week after influenza vaccination. High-dose
steroid treatment was promptly initiated, but hemodialysis was needed for 9 days.
Maintained steroid treatment for 2 weeks was associated with complete recovery of
renal function and skin lesions. CONCLUSION: As influenza vaccination is
increasingly used, physicians should be aware of the potential serious side
effect of leukocytoclastic vasculitis, particularly in patients who are
immunocompromised either due to an underlying disorder or as a treatment-related
side effect.
PMID- 17028457
TI - Cancer and thrombosis: managing the risks and approaches to thromboprophylaxis.
AB - Patients with cancer are at increased risk of venous thromboembolism (VTE)
compared with patients without cancer. This results from both the prothrombotic
effects of the cancer itself and iatrogenic factors, such as chemotherapy,
radiotherapy, indwelling central venous devices and surgery, that further
increase the risk of VTE. Although cancer-associated thrombosis remains an
important cause of morbidity and mortality, it is often underdiagnosed and
undertreated. However, evidence is accumulating to support the use of low
molecular-weight heparins (LMWHs) in the secondary prevention of VTE in patients
with cancer. Not only have LMWHs been shown to be at least as effective as
coumarin derivatives in this setting, but they have a lower incidence of
complications, including bleeding, and are not associated with the practical
problems of warfarin therapy. Furthermore, a growing number of studies indicate
that LMWHs may improve survival among patients with cancer due to a possible
antitumor effect. Current evidence suggests that LMWHs should increasingly be
considered for the longterm management of VTE in patients with cancer.
PMID- 17028458
TI - Schwa elision in fast speech: segmental deletion or gestural overlap?
AB - Pretonic schwa elision in fast speech (e.g. potato --> [pt]ato, demolish -->
[dm]olish) has been studied by both phonologists and phoneticians to understand
how extralinguistic factors affect surface forms. Yet, both types of studies have
major shortcomings. Phonological analyses attributing schwa elision to across-the
board segmental deletion have been based on researchers' intuitions. Phonetic
accounts proposing that elision is best characterized as gestural overlap have
been restricted to very few sequence types. In this study, 28 different [#CeC-]
sequences are examined to define appropriate acoustic criteria for 'elision', to
establish whether elision is a deletion process or the endpoint of a continuum of
increasing overlap, and to discover whether elision rates vary for individual
speakers. Results suggest that the acoustic patterns for elision are consistent
with an overlap account. Individual speakers differ as to whether they increase
elision only at faster speech rates, or elide regardless of rate. Phonotactic
legality per se does not affect elision rates, but speech rate may affect the
phonological system by causing a modification of the standard timing
relationships among gestures.
PMID- 17028459
TI - Testing licensing by cue: a case of Russian palatalized coronals.
AB - The hypothesis 'licensing by cue' by Steriade holds that phonological contrasts
are maintained in environments that provide better acoustic cues to the contrasts
and are neutralized in environments that provide poorer acoustic cues or no cues.
This paper tests the hypothesis by examining the distribution of a phonological
contrast--the Russian plain/palatalized coronal stops /t/ and /tj/ in various
syllable-final contexts. The results of a series of acoustic and perceptual
experiments presented in this paper provide some support for the hypothesis: the
relative salience of releases in different word boundary contexts (_#k > _#n,
_#s) correlates strongly with the general patterns of neutralization of the
contrast in similar word-internal contexts (_k > _n, _s) in Russian and other
related languages. At the same time, the relative salience of VC transitions in
different vowel contexts (a_ > u_ > i_) has apparently little to do with attested
patterns of neutralization. The results suggest that some perceptual cues are
phonologically more relevant than others, providing evidence for interactions
between phonetics and phonology more complex than predicted by the hypothesis.
PMID- 17028460
TI - On the prosody of Orkney and Shetland dialects.
AB - The aim of this study is to find experimental support for impressionistic claims
that there are prosodic differences between the dialects of Orkney and Shetland.
It was found that native listeners had no difficulty in discriminating between
Orkney and Shetland dialects when presented with speech fragments containing only
melodic information. The results of a subsequent acoustic investigation revealed
that there is a striking difference in pitch-peak location, which can be
characterised as a shift in the location of the entire rise, i.e. both the onset
and the peak. Shetland has early alignment, whereas the accent-lending rise in
Orkney occurs late, so that in disyllabic words with initial stress the pitch
peak does not coincide with the stressed syllable, but is delayed until the post
stress syllable. Finally, the perceptual relevance of the prosodic parameters
identified in the acoustic study was investigated.
PMID- 17028461
TI - Prosodic shaping of consonant gemination in Cypriot Greek.
AB - This paper presents an experimental investigation of durational variation in
lexical and post-lexical geminate alveolar laterals, under different stress
conditions, in Cypriot Greek. Lexical geminates are found to be longer than post
lexicals, and both geminates and non-geminates are longer in word-initial
position. The durational distinction is robust in all conditions, but
particularly for word-initial lexical geminates. Post-lexical geminates and word
initial lexical geminates are significantly longer when pre-stress. Word-initial
geminates are longer when preceded by a word-final nasal (the condition for post
lexical gemination), thus creating a kind of 'supergeminate' consonant and
indicating that word-final nasals are not deleted, as has previously been thought
to be the case. Implications for the phonological analysis of Cypriot Greek
geminates and the role of prosodic and phonotactic restrictions are considered.
PMID- 17028464
TI - High level of expression of alpha-fetoprotein receptor in gastric cancers.
AB - The expression of the receptor for alpha-fetoprotein (AFP-R) was examined
immunohistochemically in 47 cancer and 14 benign human gastric tissues. Rabbit
polyclonal antibody against human AFP-R was used for immunohistochemical
staining. Thirty-four of the 47 cancer tissues expressed AFP-R showing granular
or reticular staining on the cancer cell surface, while only 2 of 61 control
cases (14 benign gastric tissues and 47 nonmalignant tissues adjacent to cancer)
showed faint and homogeneous staining in the cytoplasm of noncancerous cells.
There was a significant difference in staining intensity between the cancerous
and noncancerous groups. However, no statistically significant difference in
staining intensity was found among the groups of well-differentiated, moderately
differentiated and poorly differentiated adenocarcinomas. On the other hand, the
staining intensity of signet ring cell carcinoma was significantly weaker than
that of the three adenocarcinoma groups. The high level of AFP-R expression in
gastric cancers may allow the use of AFP-R as a new clinically useful marker of
gastric cancer in the tissue level.
PMID- 17028465
TI - Do serum angiogenic growth factors provide additional information to that of
conventional markers in monitoring the course of metastatic breast cancer?
AB - OBJECTIVE: Our work evaluated the potential role of basic fibroblast growth
factor (bFGF) and vascular endothelial growth factor (VEGF) serum levels with
respect to that of conventional serum tumour markers, CEA and CA 15-3, in
monitoring the course of metastatic breast cancer in 56 female patients treated
with cytotoxic chemotherapy. METHODS: VEGF and bFGF concentrations were
determined using a quantitative sandwich enzyme immunoassay technique. The
positive predictive value (PPV) of each marker and of marker combinations for
different types of clinical response was calculated. RESULTS: The highest PPV for
overall disease control was shown by bFGF (70%), which also showed the highest
PPV for both partial response (36.4%) and stable disease (63.2%). CEA showed the
highest predictive value for progression (69.2%). A combined increase in CEA and
bFGF or VEGF was associated with disease progression in all patients.
CONCLUSIONS: Information provided by angiogenic factor levels seems to be
independent of and is possibly complementary to that provided by conventional
serum markers. bFGF showed the maximum predictive value for disease control and
provided additional information to that obtained from CEA or CA 15-3 evaluation.
It could therefore be a promising candidate for monitoring response to
chemotherapy in advanced breast cancer.
PMID- 17028466
TI - [Hemolysis, elevated liver enzymes, and low platelet count syndrome].
AB - HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome is a
severe, life-threatening pregnancy pathology, which occurs in 0.2-0.8% of all
pregnancies, and approximately 10% (2-20%) of pregnancies are complicated with
severe preeclampsia. This syndrome usually develops in the third trimester of
pregnancy in preeclamptic patients, sometimes it occurs in the second trimester
of pregnancy, and very rarely HELLP syndrome may develop within 48-72 hours after
delivery. Diagnosis is complicated as there are no specific clinical signs,
therefore, this syndrome may be confused with other pathologies like acute fatty
liver of pregnancy, idiopathic thrombocytopenia, hemolytic uremic syndrome,
appendicitis, and etc. The patients with HELLP syndrome should be treated in the
tertiary care hospital, where appropriate diagnostics and multidisciplinary help
for mother and fetus can be assured. When the syndrome was described for the
first time, L. Weinstein recommended prompt delivery as the only possible
treatment. Current studies show that conservative treatment of patients with
HELLP syndrome is safe, without an increase in morbidity and mortality. That is
why now many authors agree that treatment approach should be based on the
estimated gestational age and the condition of the mother and fetus.
PMID- 17028467
TI - [Empiric de-escalation strategy of antibiotic treatment].
AB - Nosocomial pneumonia, especially ventilator-acquired pneumonia, has the greatest
impact on patients' management in intensive care unit. Inappropriate initial
antimicrobial treatment increases attributable and crude mortality from
ventilator-acquired pneumonia. De-escalation therapy improves short-term survival
of patients with ventilator-acquired pneumonia without increasing the emergence
of resistant organisms.
PMID- 17028468
TI - Measurement of quality of life in stroke patients.
AB - The quality of life after stroke and the methods of measuring this aspect of the
disease have been viewed with a growing interest. The measurement has been
focused on the physical, psychological, social, and functional aspects of living
and is generally based on the patients' subjective perception of his/her general
health and well-being. Seven generic measurement scales and three recently
developed stroke-specific scales have been assessed and discussed. The stroke
specific quality of life measures described in this review are as follows: the
Stroke Adapted Sickness Impact Profile, the Stroke Impact Scale, and the Stroke
Specific Quality of Life Measure. The various factors leading to a deterioration
of the quality of life and influencing the quality of life scores are discussed
and defined. Moreover, the necessity of further research is stressed.
PMID- 17028469
TI - [Evaluation of the cosmetic effect of orbital endoimplantation after removal the
eyeball].
AB - The purpose of our study was to evaluate the cosmetic effect of endoimplantation
after removal the eyeball. The removal of the globe creates anatomic and
physiological alteration of the orbital tissue and orbital bones. A volume
deficit occurs when an eye is enucleated. Deep upper lid sulcus, ptosis, lower
lid laxity, and enophthalmus of the artificial eye together constitute the
postenucleation socket syndrome, which creates an asymmetry of the face. The
orbital prosthesis by placing it in the orbital cavity allows correcting volume
deficit, so the implant with attached extraocular muscles, together with an
artificial eye, creates an illusion of real eye. Forty patients were operated on
in Clinic of Eye Diseases of Kaunas University of Medicine Hospital. Twenty
patients underwent removal of the eye and procedure of orbital implant insertion
(main group). Twenty patients had just an eyeball removal without insertion of an
orbital implant (control group). There was a statistically significant difference
in exophthalmometry data between main and control groups (14.20+/-2.73 vs.
10.35+/-1.23 mm, respectively; p<0.05). The motility of artificial eye laterally
(4.30+/-1.66 mm), medially (3.65+/-1.23 mm), up (3.70+/-1.13 mm), and down
(3.40+/-1.19 mm) in the main group was significantly better as compared to the
control group (p<0.05), where motility of the artificial eye was 0.60+/-0.68 mm
laterally, 0.70+/-0.92 mm medially, 0.30+/-0.66 mm up, and 0.30+/-0.47 mm down.
Therefore, a much better symmetry, better movement of the artificial eye, and
less severe form of postenucleation syndrome were observed in patients who
underwent orbital endoimplantation after eyeball removal.
PMID- 17028470
TI - New surgical technique for the treatment of urinary incontinence in Clinic of
Obstetrics and Gynecology of Kaunas University of Medicine.
AB - There are various surgical methods for the treatment of female urinary stress
incontinence. The aim of this study was to evaluate the effectiveness of tension
free vaginal tape (TVT) operation based on a three-year clinical experience and
the possibility of its use in the outpatient settings. MATERIALS AND METHODS: The
patients were examined according to a standardized protocol for urinary
incontinence and were operated on according to the original "Gynecare TVT"
protocol. A total of 57 women were operated on and followed up during the study
period (02/25/2000-12/31/2002). The average age was 52 years. Out of them 31
(54.4%) women were after menopause and 56 (97.9%) gave birth. Nine women had
operations in their medical histories: five had hysterectomies and the other four
were operated on because of urinary incontinence. Besides, five women were
operated due to mixed urinary incontinence. Among the operated women, 6 had local
anesthesia, 13 had epidural, and 38 had lumbar anesthesia. The average time of
the operation was 22.3 minutes. The mean hospital stay was 4.4 days. Five
patients were hospitalized for one day. Besides TVT operation, eight patients had
anterior colporrhaphy, two patients had posterior colporrhaphy, and two patients
had "mesh" application for cystocele treatment. RESULTS: One woman had stress
urinary incontinence symptoms after operation (the effectiveness of operation was
98.2%). The main complications were: perforation of the urinary bladder was
present in 1 (1.8%) patient and infection of urinary tract - in 4 (7.0%)
patients. CONCLUSION: TVT operation is a minimal invasive, fast, safe and very
effective surgical procedure for the treatment of urinary stress incontinence,
which has to be implemented in Lithuania as a routine outpatient procedure.
PMID- 17028471
TI - [Evaluation of factors influencing effectiveness of kinesitherapy in patients
after traumatic brain injury].
AB - OBJECTIVE OF THE STUDY: To establish the factors, which have an influence on
recovery of motor and cognitive functions in patients after moderate or severe
traumatic brain injury, when kinesitherapy is applied during the acute stage of
injury and early stage of rehabilitation. MATERIAL AND METHODS: Subjects were 131
patients (99 men and 32 women) with a mean age of 39.5+/-15.9 years. Patients
were divided into two subgroups according to degree of injury: severe injury (103
subjects) and moderate injury (28 subjects). During acute stage of injury,
patients were treated at the Unit of Brain Injuries, Kaunas University of
Medicine Hospital; thereafter, 80 patients continued rehabilitation at the Unit
of Neurorehabilitation, while 51--in another rehabilitation centers. Recovery of
motor and cognitive functions was evaluated using Functional Independence
Measure: during acute stage of injury (beginning and end) and during early stage
of rehabilitation (beginning, day 25, and end). RESULTS: In order to determine
the effect of kinesitherapy, the influence of following factors was evaluated:
meningitis, cranial nerves damage, musculoskeletal system dysfunctions, plegia of
extremities, speech and cognitive dysfunctions, behavioral changes, sleep
disorders, depression, pneumonia, edema, hydrocephalus, epilepsy. The motor score
in patients after moderate traumatic brain injury at the beginning of acute stage
was 32.4+/-12.7, while in patients after severe injury it was 21.3+/-7.7
(p<0.01). At the end of this stage, the difference between subgroups was
insignificant: 61.8+/-24.0 and 60.9+/-22.5, respectively (p>0.05). At the
beginning of acute stage of injury, cognitive function score differed
significantly: in moderate injury subgroup, the score was 14.2+/-5.5, while in
severe injury subgroup - 10.0+/-4.9 (p<0.01). At the end of early stage of
rehabilitation, no significant difference in cognitive function scores was found
between subgroups: 22.3+/-8.4 and 22.5+/-8.6 scores, respectively (p>0.05).
CONCLUSIONS: Insufficient recovery of motor functions during period of
kinesitherapy was influenced by depression, pneumonia, plegia of extremities,
speech and cognitive dysfunctions, sleep disorders, dysfunctions of
musculoskeletal system, behavioral changes, while the recovery of cognitive
functions was influenced mainly by pneumonia, speech and cognitive dysfunctions,
and sleep disorders (p<0.05).
PMID- 17028472
TI - The relationship of the intensity of lens opacity with physical activity.
AB - OBJECTIVE: To study the character and the intensity of lens opacity and the
visual acuity in cataract patients and controls and to determine the association
of these indices with the subjects' physical activity. MATERIAL AND METHODS: The
lens opacity in 110 eyes of patients (n=110) aged 60.3+/-0.4 (mean+/-SEM) years
admitted to the Clinic of Eye Diseases of Kaunas University of Medicine Hospital
for cataract surgery and the lens opacity of 100 eyes of controls (n=50) aged
59.8+/-0.4 (mean+/-SEM) (p>0.05) years hospitalized in the Clinic of Skin and
Venereal Diseases was evaluated according to the Lens Opacity Classification
System, version III. Visual acuity was investigated using the Snellen chart.
Physical activity in metabolic equivalent minutes per week (MET-minutes/week) was
evaluated according to the International Physical Activity Questionnaire.
RESULTS: The means of the intensity of lens opacity of patients with cataract
were significantly higher, and the means of visual acuity and physical activity
were significantly lower, compared to controls (p<0.01-0.001). For less active
patients (<5900 MET-minutes/week) with the right eye examined, the odds ratio of
cataract was by 7.00 (95% confidence interval 2.93-16.74, p<0.001) and for those
with the left eye studied by 4.43 (95% confidence interval 1.97-9.98, p<0.001)
times higher, compared to physically active (>5900 MET-minutes/week) patients.
Physical activity was inversely correlated (r=-0.452, p<0.05) with the lens
opacity in the cortex in physically active (>5900 MET-minutes/week) subjects with
cataract who underwent the examination of the left eye. CONCLUSION: The intensity
of lens opacity and cataract are statistically significantly related to physical
activity.
PMID- 17028473
TI - [The impact of subclinical vertebral fractures on health-related quality of life
in women with osteoporosis].
AB - The aim of the study was to evaluate the impact of subclinical vertebral
fractures on health-related quality of life in women with postmenopausal
osteoporosis. A disease-specific instrument, Quality of Life Questionnaire of the
European Foundation for Osteoporosis (QUALEFFO-41) questionnaire, developed to
measure quality of life in patients with osteoporosis, was used. A total of 120
postmenopausal women who came for consultation were examined. Subclinical
vertebral fractures were identified by standardized lateral radiographs. Patients
were divided into three study groups according to bone mineral density and
incident fracture status: group 1 (control group)--40 women without osteoporosis,
group 2--40 women with osteoporosis, but without vertebral fracture, and group 3-
40 women with subclinical osteoporotic vertebral fracture. The last group was
divided into two subgroups: with one fracture and with multiple vertebral
fractures. The mean total score of the QUALEFFO-41 for the control group was
34.12 (95% CI 30.27-37.96), for the group with osteoporosis, but without
vertebral fracture--36.51 (95% CI 33.56-39.45), and for the group with non
clinical osteoporotic vertebral fracture--35.69 (95% CI 32.08-39.29). There were
statistically significant differences in domains A (pain) and E (social function)
between women with one non-clinical vertebral fracture and control group. Our
results showed no statistically significant differences in health-related quality
of life, assessed QUALEFFO-41, between women with subclinical vertebral fractures
and control group. Women with one subclinical vertebral fracture showed
statistically significant worse results in pain, social function, and general
health perception domains. Significantly greater changes in body appearance were
noted among women with multiple subclinical vertebral fractures.
PMID- 17028474
TI - [The results of thyroid ultrasound examination in randomly selected
schoolchildren].
AB - Iodine deficiency is an actual problem of public health and mostly manifests as
enlargement of the thyroid (goiter). OBJECTIVE: The aim of the study was to
determine the prevalence of goiter using different evaluation criteria and to
establish the relationship between changes in thyroid volume and dimensions of
the body. MATERIAL AND METHODS: Thyroid palpation and ultrasound examination were
performed in 310 (7-11-year-old) randomly selected schoolchildren from two
Lithuanian nearby small towns (Birzai and Rokiskis) in the district with lowest
urinary iodine excretion (5.4 and 4.5 microg/dl). The size of thyroid gland was
determined by inspection and palpation using the World Health Organization
criteria. All children were examined ultrasonographically; thyroid volume was
assessed by two criteria: F. Delange (1997) and M. B. Zimmermann (2004). RESULTS:
There were no differences in means and medians of age and all body parameters
(height, weight, body surface area, body mass index) in boys and girls of the
same age. Higher means and medians of the body surface area in all age groups
were found in Birzai as compared to Rokiskis (p<0.05). Comparing body mass index
of all investigated schoolchildren with upper limits (97th percentile) of body
mass index of normal British children, no statistically significant difference in
the prevalence of obesity between towns was observed (1.9% - in Rokiskis, 5.0% -
in Birzai; p>0.05). Grouping the children according to age revealed a higher
prevalence of goiter in Birzai as compared to Rokiskis (88% vs. 63%,
respectively, according to M. B. Zimmermann and 25% vs. 10%, respectively,
according to F. Delange; p<0.05). There was no significant difference in the
prevalence of goiter between the towns when children were grouped by body surface
area. In all groups by age and body surface area, the mean thyroid volume
exceeded 97th percentile by M. B. Zimmerman and did not exceed by F. Delange.
CONCLUSIONS: The prevalence of goiter, assessing the thyroid volume in 7-11-year
old children by the different criteria, is significantly different. We recommend
using the criteria based on body surface area in order to evaluate the
constitutional characteristics of individual child's development.
PMID- 17028475
TI - Association between environment and psycho-emotional stress experienced at sea by
Lithuanian and Latvian seamen.
AB - This is the first scientific research in Lithuania and Latvia that involves a
national cross-sectional study of the seamen of two different countries-
Lithuania and Latvia--including the evaluation and comparison of seamen's working
environment, lifestyle, health, the prevalence of health-damaging risk factors,
as well as the causative relationships between the objective and subjective
health evaluation and psycho-emotional stress experienced at sea. The aim of the
study was to investigate the frequency and predictors of the psycho-emotional
stress experienced at sea by Lithuanian and Latvian seamen. Beside the common
statistical methods, the logistic stepwise regression analysis was used in order
to find the risk factors of the self-rated stress and to correct the risk
estimates for the confounding variables. Seamen of both countries indicated that
they experienced psycho-emotional stress after, on the average, 2.7-2.8 months
from the beginning of the voyage. More than one-half (57.5%) of Latvian seamen
stated that they had experienced psycho-emotional stress, whereas the respective
percentage of Lithuanian seamen was smaller (46.1%). The obtained findings showed
that, having evaluated the influence of all the analyzed factors (industry
specific, health and lifestyle, medical and demographic), there was no
significant difference between the seamen of the two countries concerning the
experience of psycho-emotional stress on the ship. The following main prognostic
factors related to the occurrence of psycho-emotional stress on the ship were
determined: higher or specialized secondary education level (p<0.001), age of 35
44 or 45-54 years (p<0.01), 9-10 or 11-12 hours of work per day when being
exposed to detrimental factors (p<0.01), the evaluation of one's health status as
"average" (p<0.05), and evaluation of one's physical capacity as "quite good" or
"average" (p<0.01). The occurrence of psycho-emotional stress was mostly
influenced by work in the environment requiring increased visual strain (p<0.001)
and vibration (p<0.05). We found that the following factors were associated with
the occurrence of psycho-emotional stress on the ship: depression that occurred
more frequently at sea than on shore (p<0.001), disturbed working and resting
regimen due to time zone changes (p<0.001), and disturbed regular sexual life
(p<0.001). Many of the unique aspects of seafaring are unchangeable. However, it
possible to modify, supplement, or develop new strategies to reduce the impact
these factors have on the health of individual seafarers.
PMID- 17028476
TI - [An update on multiple insulin injection therapy in type 1 and 2 diabetes].
AB - Achieving and maintaining glycemic control (glycated hemoglobin--HbA(1c)< or
=7.0% according to American Diabetes Association and < or =6.5% according to
International Diabetes Federation) is the primary goal in treating diabetes,
which lowers the risk for diabetes-related complications. Insulin therapy is
essential for type 1 diabetes treatment. Insulin therapy in type 2 diabetes is
initiated when glycemic control is inadequate despite the combination of
antihyperglycemic drugs. The type of insulin therapy is selected according to the
patient's lifestyle and needs. Multiple insulin injection therapy and premixed
insulin therapy are usually administered. In multiple insulin injection therapy,
basal insulin is administered one or two times a day, and regular human insulin
or rapid-acting insulin analog is administered with each meal. The duration of
action of regular insulin is 6-8 hours; therefore, the risk for postprandial
hypoglycemia is increased. The action of novel insulin analogs (rapid- and long
acting) closely mimics physiological insulin secretion. Three rapid-acting
insulin analogs are currently available: insulin lispro, insulin aspart, and
insulin glulisine. Insulin glulisine is the most recently approved rapid-acting
insulin analog. It is safe, flexible, and effective in achieving target
postprandial glycemic control. Moreover, the pharmacokinetics of insulin
glulisine does not depend on the amount of subcutaneous fat. Basal insulins
include intermediate-acting human insulins (neutral protamine Hagedorn) and long
acting insulin analogs (insulin glargine, insulin detemir). The latter are the
optimal choice covering basal insulin requirement. Compared to neutral protamine
Hagedorn insulin, long-acting insulin analogs have no pronounced concentration
peak and reduce nocturnal hypoglycemia risk and weight gain.
PMID- 17028477
TI - Optimizing hypertension control in patients with multiple cardiovascular risk
factors.
PMID- 17028478
TI - Managing hypertension: state of the science.
AB - Hypertension management is both routine and a challenge. Updated guidelines
emphasize the need to achieve increasingly stringent blood pressure goals to
reduce cardiovascular morbidity and mortality; however, the blood pressure of
many patients who have been diagnosed with hypertension is not well controlled.
Treating prehypertension nonpharmacologically may preempt the progression to
hypertension, whereas early and aggressive management of hypertension with
antihypertensive agents reduces short- and long-term cardiovascular risk.
Treatment decisions should follow current guidelines while evaluating recently
published clinical studies. When choosing between agents from different
therapeutic classes or combining agents, physicians should consider current and
targeted blood pressure levels, the patient's demographic profile, the presence
or absence of compelling cardiovascular and metabolic indications, other
comorbidities, and concurrent medication(s).
PMID- 17028479
TI - Managing multiple cardiovascular risk factors: state of the science.
AB - Cardiovascular risk comprises genetic, lifestyle, and metabolic factors. Risk
factors frequently occur simultaneously, compounding the risk for a
cardiovascular event. The most commonly occurring metabolic clustering includes
elevated blood pressure, dyslipidemia (high triglyceride levels and low levels of
high-density lipoprotein cholesterol), and impaired glucose tolerance or type 2
diabetes mellitus. Together with visceral obesity, this clustering of risk
factors is known as the metabolic syndrome. Although the definition of the
metabolic syndrome and its relevance in clinical practice are the subject of
discussion, there is emerging consensus about the importance of treating all risk
factors early and aggressively. Recent evidence suggests that new-onset diabetes
mellitus and microalbuminuria are independent risk factors that should be
considered when assessing composite cardiovascular risk. Treatment should be
tailored to a patient's risk profile, with consideration of the varying effects
that agents of different therapeutic classes have on cardiovascular and metabolic
parameters.
PMID- 17028480
TI - Incremental risk-factor reduction improves overall cardiovascular benefit: is it
time to abandon the silos?
PMID- 17028483
TI - Relation of left ventricular hypertrophy to regional cerebral blood flow: single
photon emission computed tomography abnormalities in essential hypertension.
AB - Several reports have shown that left ventricular hypertrophy (LVH) is an
independent predictor of acute cerebrovascular events. The aim of the present
study was to investigate the relationship between LVH and cerebral blood flow in
middle-aged patients with essential hypertension. Forty never-treated
hypertensive patients (24 men, 16 women, aged 50-60 years) without clinical
evidence of target organ damage were studied. Regional cerebral blood flow was
measured by means of single photon emission computed tomography of the brain.
Twenty-nine patients showed echocardiographic criteria of LVH; 11 patients did
not show this feature. No differences were found in regional cerebral blood flow
ratio of all brain areas studied between hypertensives with or without LVH except
for the striatum area. The regional cerebral blood flow ratio was significantly
reduced in the striatum region of hypertensive patients with LVH, compared with
patients without LVH (91.5+/-7.4 vs 98.1+/-8.3; P=.023). This relationship
remained significant after adjusting for blood pressure. The authors conclude
that the presence of LVH in middle-aged patients with essential hypertension is
associated with a reduction of regional cerebral blood flow in the striatum area.
PMID- 17028482
TI - A randomized, double-blind trial comparing the effects of amlodipine
besylate/benazepril HCl vs amlodipine on endothelial function and blood pressure.
AB - Evidence suggests that renin-angiotensin-aldosterone system inhibition
ameliorates endothelial dysfunction. The authors examined the effect of
amlodipine besylate/benazepril HCl combination treatment compared with amlodipine
besylate monotherapy in modulating endothelial dysfunction. This multicenter,
double-blind, 12-week study randomized 70 hypertensive subjects with at least one
other endothelial dysfunction risk factor to amlodipine besylate/benazepril HCl
(5/20 mg/d force-titrated to 5/40 mg/d) or amlodipine besylate monotherapy (5
mg/d force-titrated to 10 mg/d). Both the combination and monotherapy produced
significant median increases from baseline in percentage flow-mediated
vasodilation (2.0% and 1.2%, respectively) and percentage change in percent flow
mediated vasodilation (25% and 16%, respectively). These improvements were
numerically larger with combination treatment, but between-group differences did
not achieve statistical significance. Reductions in systolic and diastolic blood
pressure were significantly greater (P=.0452/P=.0297) with combination treatment
(-18.6/-12.3 mm Hg) than with monotherapy (-14.8/-9.1 mm Hg). A highly positive
correlation between change in systolic blood pressure and change in percent of
flow-mediated vasodilation was demonstrated only for combination treatment.
PMID- 17028484
TI - Changing patterns of initial drug therapy for the treatment of hypertension in a
Medicaid population, 2001-2005.
AB - Thiazide diuretics have been recommended as one preferred choice for the initial
treatment of hypertension. This study was undertaken to determine whether Maine
physicians initiating monotherapy for newly diagnosed hypertensive patients from
2001-2005 used this guideline. The Maine Medicaid database was searched for the
drug classes used to initiate monotherapy for patients followed for at least 6
months. A total of 5373 patients were included. In 2001, the use of beta-blockers
was 23.5%, diuretics 17.5%, angiotensin-converting enzyme inhibitors 37.5%,
calcium channel blockers 9.5%, angiotensin receptor blockers 3.8%, and others
8.2%. By 2005, the use of beta-blockers was 27.8%, diuretics 25.5%, angiotensin
converting enzyme inhibitors 30.9%, calcium channel blockers 6.4%, angiotensin
receptor blockers 1.6%, and others 7.7%. There was an increase in the use of
angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in
diabetics but no other condition affected drug choice. Although there was an
increase in the use of diuretics as initial therapy in 2003 and 2004, this
decreased in 2005. The increase in initial diuretic use was not reflected in
patterns of ongoing antihypertensive use from 1997 to 2005. There appears to have
been limited impact from the guidelines on initial drug choice and even less so
on ongoing drug therapy.
PMID- 17028485
TI - Insulin resistance, diabetes, hypertension, and renin-angiotensin system
inhibition: reducing risk for cardiovascular disease.
AB - Insulin resistance, diabetes mellitus, and hypertension are associated with
significant cardiovascular morbidity and mortality. Lifestyle modifications
effectively decrease the risk of progression to diabetes in high-risk patients,
but intensive interventions can be costly and difficult for patients to maintain.
The addition of pharmacotherapy is often necessary to treat hyperglycemia and
hypertension and lower the risk of cardiovascular complications. Clinical trial
data suggest the use of insulin-sensitizing and antihyperglycemic agents to delay
the progression to diabetes. Similarly, analysis of data from clinical trials of
angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers
indicate that the use of these agents results in fewer cases of new-onset
diabetes among patients with hypertension, when compared with other
antihypertensive agents. Angiotensin II has direct and indirect effects on
insulin and its signaling pathways, providing support for the biologic mechanism
underlying the benefits of renin-angiotensin system inhibition in preventing
diabetes and cardiovascular events. Clinical trials now under way will further
evaluate the role of renin-angiotensin system inhibition in preventing diabetes
and its microvascular and macrovascular complications.
PMID- 17028486
TI - The ASCOT Trial--are beta-blockers still useful as antihypertensive medication?
PMID- 17028487
TI - Prehypertension: an important preventive medicine concept--or marketing ploy?
PMID- 17028488
TI - Drug interactions and drugs that affect blood pressure.
AB - Many antihypertensive drugs have important interactions with drugs used for
different purposes; when these are used concomitantly, adverse effects on blood
pressure can result. Fortunately, in recent years, the drug development process
has generally discouraged the approval and marketing of antihypertensive drugs
with this problem, although some anomalies still exist (eg, telmisartan +
digoxin). Physicians who work in emergency departments are more familiar with
illicit or unregulated drugs that affect blood pressure; chief among these are
cocaine and other opioids, and methylphenidate and its congeners. The most
important prescription drugs that affect blood pressure are the nonsteroidal anti
inflammatory drugs (including selective inhibitors of the second isoform of
cyclooxygenase) and steroids. Phenylpropanolamines, some antidepressants, and
sibutramine can often be avoided, as they raise blood pressure in a significant
proportion of those who take them. Conversely, the hypertensive effects of
calcineurin inhibitors and erythropoietin are most commonly overcome by
increasing the intensity of antihypertensive drug treatment, since these drugs
are essentially unavoidable in most patients who receive them.
PMID- 17028489
TI - Managing chronic severe hypertension in pregnancy.
PMID- 17028490
TI - Does consumption of high-caffeine energy drinks affect blood pressure?
PMID- 17028491
TI - Obstructive sleep apnea syndrome.
AB - Obstructive sleep apnea syndrome is caused by upper airway collapse during
inspiration, causing intermittent hypoxemia, hypercapnia, acidosis, sympathetic
nervous system activation, and arousal from sleep. Nighttime blood pressure is
higher, but unexpectedly, daytime hypertension occurs. The prevalence of
hypertension is very high and the incidence of hypertension increases as the
number of apneic and hypopneic events per hour rises. Obesity is a major
predisposing factor for the development of obstructive sleep apnea. Daytime
sleepiness, snoring, and breathing pauses are important symptoms to elicit from
the patient or sleep partner. Resistant hypertension is an important clue.
Overnight polysomnography is required for diagnosis. Weight loss, avoidance of
nocturnal sedatives, cessation of evening alcohol ingestion, and avoidance of the
supine position during sleep are initial therapeutic actions in mild obstructive
sleep apnea syndrome. Continuous positive airway pressure is the treatment of
choice for patients unable to find relief from lifestyle changes. Blood pressure
modestly improves with treatment.
PMID- 17028492
TI - Empower women through education and access.
PMID- 17028493
TI - Negative campaign not in patients' best interest.
PMID- 17028494
TI - Breaking through obesity with gastric bypass surgery.
PMID- 17028495
TI - Acne: intervene early.
AB - "There is no single disease which causes more psychic trauma, more maladjustment
between parents and children, more general insecurity and feelings of
inferiority, and greater sums of psychic suffering than does acne vulgaris."
PMID- 17028497
TI - Evidence-based practice and the nurse practitioner.
PMID- 17028498
TI - Popular diets: what practitioners should know.
PMID- 17028499
TI - Breast cancer therapy and treatment guidelines.
PMID- 17028500
TI - Ibandronate (boniva) offers new options for osteoporosis.
PMID- 17028502
TI - Thyroid disease associated with exposure to the Nevada nuclear weapons test site
radiation: a reevaluation based on corrected dosimetry and examination data.
AB - BACKGROUND: A study was begun in 1965 to 1966 to determine whether children
exposed to radioactive iodine from nuclear weapons testing at the Nevada Test
Site from 1951 through 1962 were at higher risk of thyroid disease. In 1993, we
reported that among those examined in 1985 to 1986 (Phase II) there was an
association between radiation from the Nevada Test Site and thyroid neoplasms.
METHODS: We reevaluated the relationship between exposure to Nevada Test Site
fallout and thyroid disease using newly corrected dose estimates and disease
outcomes from the Phase II study. A prospective cohort of school children 12 to
18 years old living in Utah, Nevada, and Arizona was first examined for thyroid
disease in 1965 to 1966 and reexamined in 1985 to 1986. In the Phase II report,
2497 subjects formed the basis for this analysis. Thyroid disease, including
thyroid neoplasms and thyroiditis, was expressed as cumulative incidence and risk
ratios (RRs) with a dose-response expressed as excess risk ratio (ERR/Gy).
RESULTS: The RR between thyroid radiation dose in the highest dose group and
thyroid neoplasms increased from 3.4 (in the earlier analysis) to 7.5. The RR for
thyroiditis increased from 1.1 to 2.7 with an ERR/Gy of 4.9 (95% confidence
interval = 2.0 to 10.0). There were too few malignant thyroid neoplasms to
estimate risk. CONCLUSIONS: Persons exposed to radioactive iodine as children
have an increased risk of thyroid neoplasms and autoimmune thyroiditis up to 30
years after exposure.
PMID- 17028503
TI - Sequential meta-analysis of past clinical trials to determine the use of a new
trial.
AB - BACKGROUND: Clinical trials can be stopped early based on interim analyses or
sequential analyses. In principle, sequential analyses can also be used to decide
whether enough evidence has been gathered in completed trials to make further
trials unnecessary. We demonstrate such an application through a retrospective
analysis of clinical trials comparing ventilation methods for the treatment of
preterm newborns. METHODS: We identified 5 recent trials that compared high
frequency ventilation with conventional mechanical ventilation in the treatment
of preterm newborns. Death or chronic lung disease and chronic lung disease in
survivors were the primary clinical outcomes of interest. We applied sequential
meta-analyses to these 5 studies. RESULTS: After including the first study of the
last 5 trials in a sequential meta-analysis, the boundary of "no clinically
relevant effect" was crossed for both outcomes (death or chronic lung disease). A
sensitivity analysis using a reduction in the size of assumed clinically relevant
effect showed the same findings after 2 trials. CONCLUSIONS: Sequential meta
analyses showed that a lack of clinically relevant effect had been established
after the first of the 5 trials. If such an analysis had been conducted after the
first or second of these clinical trials, it might have led to changes in the
study design of subsequent trials or even to a reassessment of the need for
further trials.
PMID- 17028504
TI - Risks for skin and other cancers up to 25 years after burn injuries.
AB - BACKGROUND: Malignant degeneration of chronic ulcers such as nonhealed burn
wounds has been described in the literature, but this phenomenon has never been
quantified in an epidemiologic study. We investigated the risks for skin and
other cancers among patients with a prior burn. METHODS: We identified 16,903
patients from the Danish Hospital Discharge Register who had been admitted to a
hospital with a thermal or chemical burn during 1978 to 1993. The cohort was
followed for cancer in the Danish Cancer Registry through 2002, and the cancer
incidence in the cohort was compared with that in the general population of
Denmark. RESULTS: Patients with burn had 139 skin cancers, with 189 expected,
yielding a standardized incidence ratio of 0.7 (95% confidence interval = 0.6
0.9). This reduced risk was due mainly to deficits of basal cell carcinoma and
malignant melanoma, whereas the number of squamous cell carcinomas observed was
close to expected. We saw no consistent increases in risk for skin cancer in the
subgroups of patients with the most severe injuries or with the longest periods
of follow up. CONCLUSIONS: The tendency to malignant degeneration of burn scars,
described in previous reports of case series, did not result in an excess of
squamous cell carcinoma of the skin or of any other type of skin cancer during up
to 25 years' follow up of a large unselected cohort of patients hospitalized for
burn injuries.
PMID- 17028505
TI - Models for the relationship between ambient temperature and daily mortality.
AB - BACKGROUND: Ambient temperature is an important determinant of daily mortality
that is of interest both in its own right and as a confounder of other
determinants investigated using time-series regressions, in particular, air
pollution. The temperature-mortality relationship is often found to be
substantially nonlinear and to persist (but change shape) with increasing lag. We
review and extend models for such nonlinear multilag forms. DEVELOPMENT: Popular
models for mortality by temperature at given lag include polynomial and natural
cubic spline curves, and the simple but more easily interpreted linear thresholds
model, comprising linear relationships for temperatures below and above
thresholds and a flat middle section. Most published analyses that have allowed
the relationship to persist over multiple lags have done so by assuming that
spline or threshold models apply to mean temperature in several lag strata (e.g.,
lags 0-1, 2-6, and 7-13). However, more flexible models are possible, and a
modeling framework using products of basis functions ("cross-basis" functions)
suggests a wide range, some used previously and some new. These allow for stepped
or smooth changes in the model coefficients as lags increase. Applying a range of
models to data from London suggest evidence for relationships up to at least 2
weeks' lag, with smooth models fitting best but lag-stratified threshold models
allowing the most direct interpretation. CONCLUSIONS: A wide range of multilag
nonlinear temperature-mortality relationships can be modeled. More awareness of
options should improve investigation of these relationships and help control for
confounding by them.
PMID- 17028506
TI - Prospective study of plasma folate, vitamin B12, and cognitive function and
decline.
AB - BACKGROUND: The relation between B vitamins and cognitive decline is
controversial. In this study, we explored the association of plasma folate and
vitamin B12 with cognitive function measured approximately 10 years later.
METHODS: We determined plasma folate and vitamin B12 levels from blood samples
collected in 1989 to 1990 and initially evaluated cognition in 1995 to 2001 among
635 women, age 70+ years, from the Nurses' Health Study. In a subset of 391, 3
repeated cognitive tests were completed for evaluation of cognitive decline over
4 years; repeated testing is ongoing for the remaining women. Our primary outcome
was a global composite score of 6 neuropsychologic tests administered by
telephone. We used linear regression models to estimate multivariable-adjusted
mean cognitive performance across quartiles of the vitamins and longitudinal
models for cognitive decline. RESULTS: Higher vitamin levels were not associated
with either initial cognitive performance or subsequent cognitive decline. Mean
difference in initial global score for top versus bottom quartiles was 0.06
standard units for folate (95% confidence interval [CI] = -0.10 to 0.22) and 0.15
units for vitamin B12 (0.00 to 0.31). There were no dose-response trends for
either nutrient. Women with high levels of both nutrients initially performed
better than women low in both nutrients (global score, mean difference = 0.34;
95% CI = 0.05 to 0.62); this association did not hold for subsequent cognitive
decline. CONCLUSIONS: Combined B vitamin deficiency may be associated with
impaired cognition, but in these healthy, well-nourished women, plasma folate and
vitamin B12 were not related to cognitive function.
PMID- 17028507
TI - Maternal use of selective serotonin reuptake inhibitors and risk of congenital
malformations.
AB - BACKGROUND: Human data on the teratogenicity of selective serotonin reuptake
inhibitors (SSRIs) are limited. We examined the association between SSRI use
during early pregnancy and the risk of congenital malformations in the offspring.
METHODS: In a population-based cohort study from Denmark, we identified 1051
women who filled prescriptions for SSRIs from 30 days before conception to the
end of the first trimester; of those, 453 filled the prescription during the
second or third pregnancy month. We included 150,780 women with no SSRI
prescriptions as a reference cohort. Drug use data were extracted from
prescription databases. Data on congenital malformations and potential
confounders were extracted from hospital discharge registries and the National
Birth Registry. RESULTS: The 150,780 women with no SSRI prescriptions gave birth
to 5112 (3.4%) children with congenital malformations. The 1051 women with SSRI
prescriptions any time during early pregnancy gave birth to 51 (4.9%) children
with congenital malformations. The corresponding adjusted relative risk (aRRs)
was 1.34 (95% confidence interval = 1.00-1.79). The 453 women with prescriptions
during the second or third month of pregnancy gave birth to 31 (6.8%) children
with congenital malformations. The corresponding aRR was 1.84 (1.25-2.71).
CONCLUSIONS: We found an increased risk of congenital malformations after
exposure to SSRIs in early pregnancy. It is unclear whether the effects were
causal or due to factors related to the underlying disease. There was no evidence
that the association was specific to particular malformations.
PMID- 17028509
TI - Systemic immune response to Trichomonas vaginalis infection during pregnancy.
AB - OBJECTIVE: The objective of this study was to characterize the systemic immune
response in women with trichomoniasis in pregnancy as compared with uninfected
women. STUDY DESIGN: A nested case control study was performed on 195 serum
samples. Serum concentrations of cytokines, chemokines, and C-reactive protein
(CRP) were compared between infected and uninfected women. Cytokines and
chemokines were measured using a multiplex bead assay. The CRP concentrations
were determined using a standard enzyme-linked immunosorbent assay method.
RESULTS: The median serum concentration of granulocyte-macrophage colony
stimulating factor (GM-CSF) was significantly higher in the trichomonas-infected
group compared with the uninfected group (8.9 pg/mL vs. 5.7 pg/mL; P <0.001). The
mean log-transformed CRP values were higher in the infected group compared with
the uninfected group (1.66 vs. 1.27; P = 0.03). CONCLUSIONS: The results of this
study suggest that trichomoniasis during pregnancy can lead to a systemic immune
response in some women as exhibited by elevation in the serum concentrations of
both GM-CSF and CRP.
PMID- 17028508
TI - Safety and tolerability of methylphenidate in preschool children with ADHD.
AB - OBJECTIVE: To report on the safety and tolerability of methylphenidate (MPH) 3-
to 5-year-old children with attention-deficit/hyperactivity disorder (ADHD)
during 1 year of treatment. METHOD: Exactly 183 children (3-5 years old) entered
a treatment study of MPH, consisting of a 1-week open-label lead-in (n=183); a 5
week placebo-controlled, double-blind phase (n=165); a 5-week double-blind,
parallel phase (n=114); and 10 months of open-label maintenance (n=140 entered,
95 completed). Mean total daily MPH doses rose from the titration trial best
dose, 14.1 (+/-8.1) mg/day, to 20.5 (+/-9.7) mg/day mean total daily dose at the
end of maintenance. Pulse, blood pressure, and the presence of treatment emergent
adverse events (AEs), parent and teacher AE ratings, and vital signs were
recorded in each phase. RESULTS: Thirty percent of parents spontaneously reported
moderate to severe AEs in all study phases after baseline. These included
emotional outbursts, difficulty falling asleep, repetitive behaviors/thoughts,
appetite decrease, and irritability. During titration, decreased appetite
(chi=5.4, p<.03), trouble sleeping (chi=5.4, p<.03), and weight loss (chi=4.0,
p<.05) occurred statistically more often on MPH than on placebo. During
maintenance, trouble sleeping and appetite loss persisted and other MPH-related
AEs decreased. There were transient, one-time pulse and blood pressure elevations
in five children. Twenty-one children (11%) discontinued because of drug
attributed AEs. CONCLUSIONS: Eleven percent of preschoolers discontinued
treatment because of intolerable MPH AEs. Of the serious AEs reported, one
occurred in baseline, two in lead-in, three in titration, one in parallel, and
one in maintenance. Only one was possibly related to MPH.
PMID- 17028510
TI - Pelvic examination findings and Chlamydia trachomatis infection in asymptomatic
young women screened with a nucleic acid amplification test.
AB - BACKGROUND: Nucleic acid amplification tests (NAATs) allow chlamydia screening in
asymptomatic women who otherwise may not have pelvic examinations. How often
these women have examination findings that may prompt empiric therapy is unclear.
OBJECTIVE: The objective of this study was to assess the relationship of
chlamydia with pelvic examination findings in asymptomatic women screened by
NAAT. METHODS: The authors conducted a retrospective analysis of clinical data
from 577 young asymptomatic women screened by chlamydial transcription-mediated
amplification (TMA). RESULTS: TMA was positive in 68 (11.8%). The most common
examination finding was vaginal discharge (5.9%) followed by cervical ectopy
(3.6%), endocervical mucopus (2.3%) or easily induced bleeding (2.3%), and
cervical motion (1.4%) or adnexal (0.7%) tenderness. On multivariate analysis,
only easily induced bleeding or mucopus predicted chlamydia (adjusted odds ratio
[AOR] = 4.7; P = 0.010 and AOR = 4.4; P = 0.015, respectively). CONCLUSIONS:
Abnormal pelvic examination findings were infrequent in asymptomatic young women
screened by a chlamydial NAAT. However, endocervical bleeding or mucopus, when
present, predicted chlamydia.
PMID- 17028511
TI - Sexual risk behavior of married men and women in Bangladesh associated with
husbands' work migration and living apart.
AB - OBJECTIVES: This study aimed to ascertain the prevalence of sexual risk behavior
among married men and women who had, or had not, lived apart from their spouse as
a result of the husbands' work migration. METHODS: A cross-sectional survey was
conducted among a random sample of 1,175 married women and 703 married men in 2
rural areas of Bangladesh. RESULTS: Extramarital sex was reported by 64.2% (95%
confidence interval [CI] = 58.7-69.7) of 296 men and 8.6% (95% CI = 7.6-9.6) of
779 women who had lived apart from their spouse, 2 to 3 times higher than the
proportions among those who had not lived apart (P <0.05). The proportions of men
who reported sex with a female sex worker (50.7%; 95% CI = 45.0-56.4) or with
another male (5.4%; 95% CI = 2.8-8.0), while living away, were double the
proportions reporting they had done so before living away or among men who had
not lived away (P <0.05). Only 2 men had ever used had a condom during sex with
another male, and less than one third of men had used a condom during sex with a
sex worker or during marital sex. CONCLUSIONS: The sexual risk behavior of
married men living away from home may put themselves and their wives at risk for
HIV infection and other sexually transmitted diseases.
PMID- 17028512
TI - [Better management of patients with difficult asthma].
PMID- 17028513
TI - [Difficult asthma].
AB - Difficult asthma is a major issue in pulmonary medicine today because of its cost
for patients and society. Difficult asthma is asthma that remains uncontrolled
despite optimal specialist management. The validity of the diagnosis must be
reconsidered in these cases: associated or differential diagnoses may be involved
in the lack of control, and it is always necessary to assess the patient's
treatment adhesion. Sufficient time--at least a year--must be taken to get to
know the patient and to meet the objectives set. The standard asthma therapies
should be tested objectively. Severe asthma is the reality of difficult asthma
that endures despite a reaffirmed diagnosis, optimal compliance and controlled
comorbidities. Better knowledge is needed of the pathophysiology of these
patients' asthma. Improved knowledge of these phenotypes will make it possible to
develop innovative treatments. They will need to be validated in clinical
research for subsequent use that is wider but more rational because targeted at
phenotypes likely to benefit from them.
PMID- 17028515
TI - [Air pollution and cardiovascular and cerebrovascular disease: Epidemiologic
data].
AB - Recent convergent data suggest that air pollution affects the risk of acute
atherothrombotic events including both myocardial infarction and ischemic stroke.
The principal epidemiologic studies begun in the 1990s first examined the
respiratory effects of atmospheric pollution and then focused on how pollution
peaks affected cardiovascular risk. These studies used data from large
metropolitan areas in North America and Asia as well as several large European
cities to demonstrate the clear existence of a relation between air pollution and
cardio- and cerebrovascular mortality. They also observed an increase in hospital
admissions for myocardial infarctions and cerebrovascular accidents on days with
high air pollution levels. The pollutants involved have not yet been clearly
designated, but it appears that fine suspended particulate matter (PM2.5) and
gaseous pollutants such as ozone appear to contribute strongly to these harmful
effects. A complete analysis of these data shows the need for a thorough
evaluation of the cardio- and cerebrovascular risks associated with air
pollution, especially in French metropolitan areas. Precise identification of
those at high risk from specific pollutants is essential to improve targeting of
prevention strategies.
PMID- 17028514
TI - [Safety of selective serotonin reuptake inhibitor antidepressants in children and
adolescents].
AB - Some behavioral side effects of selective serotonin reuptake inhibitor (SSRI)
antidepressants have been known for a long time. Since the introduction of these
drugs in the 1990s, publications have regularly reported behavioral side effects
in children and adolescents, including excitation, motor restlessness, social
disinhibition, and above all self-injurious ideation and behavior. Clinical
trials provide only limited data. Although these data suggest that some self
injurious and suicidal behavior may indeed occur in children and adolescents
receiving SSRIs, they are too disparate to specify the frequency of these acts.
Clinical trials provide useful data about drug efficacy, but their methodology is
inappropriate for determining the frequency of such side effects. SSRI and
suicidality: the data are difficult to read. Although some epidemiologic data
suggest that SSRIs may increase the risk of occurrence of self-injurious and
suicidal behavior in children and adolescents, other epidemiologic data show that
the rate of suicide mortality in children and adolescents has decreased since the
introduction of SSRIs. No known mechanism explains how SSRIs might increase the
risk of these behavioral side effects. It is clear, however, that these effects
are not particular to children and adolescents but may also be observed among
adults. SSRIs must be used rationally and carefully in children and adolescents.
They should not be administered routinely in youth with obsessive-compulsive or
depressive disorders. Their use should be reserved for severe disorders or when
psychotherapy alone has been shown to be inadequate, and when they are used,
efficacy and side effects must be monitored carefully and frequently.
PMID- 17028516
TI - [Osteoporosis priority: Reduce the number of fractures].
PMID- 17028518
TI - [Diagnosing osteoporosis: Laboratory tests].
AB - Malignant or metabolic causes of low bone mineral density must be sought after
either a fragility fracture or the discovery of low bone density measurements.
Laboratory tests for calcium and phosphate metabolism are normal in osteoporosis.
Vitamin D deficiency is frequent and requires supplementation. Markers of bone
remodeling can be useful in cases where the treatment decision is difficult.
PMID- 17028517
TI - [Drug treatment of postmenopausal osteoporosis. What's New in 2006].
PMID- 17028519
TI - [Osteoporosis: Optimizing treatment strategy].
AB - Selection of patients for treatment is based on the assessment of their absolute
fracture risk over 10 years. Assessment of fracture risk includes not only DXA
measurement and age, the two principal risk factors, but also other clinical risk
factors. The main goal of postmenopausal osteoporosis treatment is to reduce the
risk of fragility fractures. Choice of treatment is based on drug properties,
demonstrated in clinical trials, and patients' specific fracture risks. The
minimum duration of treatment is 4-5 years, after which individual fracture risk
must be reevaluated. Combinations of available drugs are not recommended for
treatment of postmenopausal osteoporosis.
PMID- 17028520
TI - [Osteoporosis in the elderly].
AB - Osteoporosis is a frequent disease among the elderly and has major consequences
in terms of mortality, morbidity and cost. Guidelines for diagnostic procedures
are often difficult to apply in frail, elderly patients with multiple
comorbidities. Bisphosphonates are the reference treatment for the elderly,
combined with vitamin D and calcium supplementation. Vitamin D deficiency must
also be treated to prevent falls and fractures. Strontium ranelate is a promising
treatment in this population. Fall prevention is a major part of osteoporosis
management. The potential benefit of hip protectors is questionable, even in
institutionalized patients.
PMID- 17028521
TI - [Hormone replacement therapy in the management of postmenopausal osteoporosis and
prevention of fracture risk].
AB - The consequences to the bone of estrogen deficiency are early and irreversible.
Effective prevention of postmenopausal osteoporosis at the individual level
requires early screening of women at risk of fractures and their early treatment.
Hormone treatment prevents bone loss and has been proven effective in preventing
fractures, even in situations of low risk. The benefit/risk ratio of hormone
treatment can be optimized by the choice of the 'right moment' and the 'right
treatment'. HRT, administered early and for a limited period, must be integrated
into a strategy of long-term osteoporosis prevention that includes using the
(drug and nondrug) means most appropriate to the patient's age and clinical
condition and choosing the 'right moment' and 'right treatment.'
PMID- 17028522
TI - [Follow-up of osteoporosis treatment].
AB - There is no linear relation between changes in bone mineral density (BMD) and
reduction in fracture risk with antiresorptive agents. Interpretation of BMD
changes at the individual level requires calculating the smallest significant
change at each measurement center. BMD measurement is essential before
administration of antiresorptive or anabolic agents for prevention or treatment
of postmenopausal osteoporosis. Biochemical markers of bone turnover can be
monitored after 6 months of treatment. Their interpretation requires careful
assessment of their intraindividual variability.
PMID- 17028523
TI - [Management of corticosteroid-induced osteoporosis].
AB - Corticosteroid-induced osteoporosis is common but too often unrecognized, and its
management remains insufficient. Bone loss is variable from one patient to
another and thus difficult to predict, but all treated patients must be
considered at risk. There are tools to assess absolute fracture risk in this case
as there are for menopause-associated osteoporosis, and they may help guide the
clinician in decision-making. Recent guidelines help the physician to define
indications for bone mineral density testing and for therapeutic management.
Bisphosphonates are currently the first-line treatment for patients with
fractures or elevated fracture risk during corticosteroid treatment.
PMID- 17028525
TI - [Meningeal carcinomatosis].
PMID- 17028526
TI - [The future of peer review of medical articles].
PMID- 17028524
TI - [Non-corticosteroid drug-induced metabolic bone disease].
AB - After osteoporotic fracture or low bone mineral density measurements, it is
necessary to look for secondary causes of osteoporosis, such as drugs.
Corticosteroids are the most common cause of drug-induced metabolic bone disease.
Other drugs responsible for bone disease include: aromatase inhibitors, GnRH
agonists, anticonvulsants, heparin, and L thyroxin at TSH-suppressive doses.
Confirmation is required of data about neuroleptics and antivitamin K.
PMID- 17028527
TI - [Influenza: A nosocomial infection].
PMID- 17028528
TI - [Legal insecurity of doctor-patient confidentiality].
PMID- 17028530
TI - [Medical guidelines and medical practices: The example of lipid lowering
therapy].
AB - INTRODUCTION: The SPOT epidemiologic survey assessed the results of long-term
cholesterol-lowering therapy in France and the reasons why patients do or do not
meet their therapeutic objectives. OBJECTIVE: To assess the guidelines on which
doctors base their practices for cholesterol-lowering therapy and make
suggestions to improve the match between recommendations and practices. METHODS:
LDL cholesterol was measured in 2479 French outpatients in 2003 and classified
according to whether it met therapeutic objectives of 3 different scales: the
official French (AFSSAPS) recommendations issued in 2000, the physician's opinion
of the ideal level for the patient, and the physician's goal level for the
patient. Agreement between these 3 criteria was analyzed. RESULTS: French doctors
used guidelines stricter than the official recommendations to assess the
achievement of lipid-lowering objectives. DISCUSSION: Physicians rely more on
American than French guidelines. They also considered the patient's history and
clinical condition in setting individual goals.
PMID- 17028529
TI - [Nosocomial influenza outbreak in a geriatrics department: Effectiveness of
preventive measures].
AB - OBJECTIVE: To describe a nosocomial influenza outbreak and the pharmacologic and
nonpharmacologic control measures implemented in a hospital ward with beds for
acute geriatric care and rehabilitation care. METHODS: Descriptive survey
conducted in the geriatrics department of a university hospital. An influenza
outbreak occurred in February 2005 in 2 of the department's 3 separate units. The
study concerned all patients in the 2 affected units (A and B) present during the
outbreak, as well as all department staff. Once cases of influenza were
confirmed, elderly patients in contact with influenza patients received
chemoprophylaxis with oseltamivir when it became available. RESULTS: Thirty-eight
(76%) patients and 62 (38%) staff members had been vaccinated. The time from the
initial symptoms of the first case until implementation of control measures was 7
days in unit A but only 1 day in unit B, -and chemoprophylaxis of contact
patients began in 9 days and 24 hours respectively. The attack rate was 38% in
the 38 vaccinated patients and 29% in the 14 unvaccinated patients (NS). All
cases met the definition of nosocomial infection. No deaths imputable to
influenza occurred during the outbreak. The implementation of the
nonpharmacologic measures aimed at preventing spread of the outbreak presented no
particular difficulty, except for compliance with geographic isolation of some
patients with dementia and influenza. The difference between the attack rates for
the two sectors (48% for unit A and 28% for unit B) suggests that the preventive
measures were effective. Tolerance to chemoprophylaxis with oseltamivir was good.
CONCLUSION: This study confirmed that influenza can affect elderly hospital
patients, even those in whom the vaccination rate is high, and that rapid
detection of the outbreak and immediate implementation of pharmacologic and
nonpharmacologic preventive measures can limit its spread.
PMID- 17028531
TI - [Health behavior of healthcare personnel: The European Presst-Next Study].
AB - OBJECTIVES: The objective of the NEXT (Nurses' Early Exit) study was to identify
the organizational and health factors in the 10 participating countries
associated with job satisfaction of nurses and nurses' aides or with their desire
to change occupation or stop working prematurely. METHODS: Questions about health
were somewhat more detailed in the French version of the questionnaire and
allowed us to determine health behaviors of this representative sample of French
caregivers (PRESST: Promotion of Health and Job Satisfaction of European
Healthcare Workers [www.next-study.net; www.presst-next.fr]). RESULTS: Of the
6980 (796 men and 6184 women) nurses and nurses' aides studied in late 2002 and
early 2003, 32.6% reported that they smoked at least occasionally and 24.3%
regularly. Only 24.4% of the staff in our sample exercised at least weekly.
Overweight was observed in 27,6% of the sample, mostly women (42% of men and
24.7% of women), and obesity affected 6,4% of men and 7% of women. Overweight was
slightly less frequent than among the general adult population of France, 39.8%
according to the CREDES SPS survey in 2002, but these healthcare workers were
younger. On the whole, burnout was higher among French caregivers than among
those from other European nations in the Next study. CONCLUSION: This study
demonstrates the need to conduct and assess interventions for the dual purpose of
(1) reducing the morbidity and mortality associated with the conditions most
sensitive to these risk factors in healthcare personnel and (2) improving their
knowledge, motivations and credibility in providing health education to patients.
PMID- 17028532
TI - [Smoking cessation counseling center in a French hospital: Effectiveness at one
year and predictors of outcome].
AB - OBJECTIVE: To assess the effectiveness at 1 year of a hospital clinic providing
individual management of persons seeking to stop smoking and the factors
predictive of failure. METHODS: This prospective descriptive study included
smokers seeking assistance at this hospital clinic over a 1-year period. This
analysis excludes persons with schizophrenia and those who came only to a first
consultation. Treatment methods were those recommended by the 1998 consensus
conference: nicotine substitutes or slow-release bupropion, depending on the
level of nicotine dependence, cognitive-behavioral therapy appropriate for
smoking in all cases, and the prescription before cessation of a selective
serotonin re-uptake inhibitor (SSRI) for patients with anxiety or depressive
disorders. Assessment was based on patients' self-report at 3 months, 6 months
and 1 year. RESULTS: Of 99 smokers who came for at least one consultation, 38
were excluded and 61 were considered in the analysis. At one year, 18 patients
(29.5%) were still not smoking. Of the 43 patients who resumed smoking, 27 (63%)
did so during the first three months after cessation. According to the
multivariate analysis, only female sex (p = 0.0173) and early end to follow-up (p
= 0.0023) were significantly associated with the risk of relapse at 1 year.
CONCLUSION: The study confirmed the usefulness of specialized medical support
over a one-year period and highlighted the difficulties of smoking cessation for
women, who appear to need a new not yet invented approach. The other standard
factors predictive of failure were not observed, possibly because of either the
broad prescription of SSRIs in cases of anxiety- or depression-related
comorbidity or the statistical limitations associated with the population size.
PMID- 17028533
TI - [Use and misuse of intravenous drug administration in a department of internal
medicine].
AB - AIM: Numerous intravenously-administered medications are also available in
equally effective oral forms. To assess the number of avoidable intravenous
infusions, we retrospectively analyzed consecutive infusions prescribed in a
department of internal medicine. METHODS: Between November and December 2004, we
analyzed all patients who received at least one intravenous drug during
hospitalization. Intravenous administration was considered unavoidable when
prescribed for no more than 2 days in a patient unstable at admission, when oral
administration or feeding was impossible, or when the drug was not available in
oral form. RESULTS: During the study period 133 patients were admitted to the
department. In all, 65 infusions were prescribed, 30% of which lasted more than 2
days for no medical reason. Four intravenous antibiotics were prescribed in
patients when their antibiotic susceptibility tests indicated that another oral
antibiotic could easily be given. Infusions for 16 other patients continued
longer than 48 hours, although the oral route was not contraindicated in these
patients and the medication was available in oral form. CONCLUSION: Systematic
analysis of the daily prescriptions may be helpful in preventing or shortening
use of intravenous medications and thereby decreasing iatrogenic infections and
injuries, length of hospitalization, and costs.
PMID- 17028534
TI - [Consultations with infectious disease specialists for patients in a teaching
hospital: Adherence in 174 cases].
AB - OBJECTIVES: In a teaching hospital where infectious disease specialists were
routinely consulted for infections in patients in other departments, we sought to
assess adherence to the specialists' recommendations, identify the factors
influencing adherence, and measure the proportion of nosocomial infections among
these consultations. METHODS: We collected data from intrahospital consultations
with infectious disease specialists over a 4-week period. Afterwards (48 hours
later), a physician and pharmacist collected all prescriptions for anti
infectious agents (dose, drug, combinations) and other orders (laboratory tests,
radiology examination, isolation) for each patient. RESULTS: There were 174
infectious disease consultations requested for 143 inpatients during the study
period. Anti-infectious agents were prescribed for 52.4% of patients, modified
for 22.4%, and stopped for 9.1%; 16.1% neither had nor required such treatment.
The rate of adherence to the specialists' recommendations was 84.6% for anti
infectious prescriptions and 77.4% for other orders. The factors associated with
adherence were a bedside consultation (p = 0.04) and a recommendation to stop
rather than modify anti-infectious treatment (p = 0.02). Roughly 40% of the
patients (n = 57) had a nosocomial infection, most often during hospitalization
for surgery (53.1% versus 29.1%, p < 0.01). Consultations were requested for 20%
of the nosocomial infections observed at Grenoble University Hospital (based on
annual prevalence in 2005). CONCLUSIONS: The specialist's presence at the
patient's bedside has an impact on staff adherence to recommendations. These
specialists play a vital role in managing nosocomial infections, which account
for more than a third of these intrahospital' consultations.
PMID- 17028535
TI - [Changes in prenatal ultrasound practices after the Perruche decision and Law no.
2002-303 dated 4 March 2002].
AB - OBJECTIVE: The aim of this study was to evaluate the effects of French law (court
rulings in the Perruche decision and its progeny as well as the statute enacted
on March 4, 2002 to reverse or moderate this jurisprudence) on physicians'
prenatal diagnosis and fetal medicine practices. METHODS: We sent questionnaires
to 186 physician-ultrasonographers in two French districts, inquiring about
changes in their daily practice and their provision of information to and
communication with the future parents, as well as their opinions about the future
of their specialization. RESULTS: We received 54 responses (29%): 40% of
respondents found it more difficult to tell patients about fetal anomalies.
Written and oral information, medical reports and explanations about the
limitations of ultrasound have improved substantially in content for 64% and are
better used for 42%. Some clinicians (24.1%) report that they take the future
parents' emotions into account more often. Some try to be more distant (13%) or
more neutral (9.3%). More than half (51.9%) request the opinion of a center for
prenatal diagnosis and fetal medicine more often and 20.4% request karyotyping
more often. In all, 7.4% believe that their counseling now leads more often
towards abortions. CONCLUSION: Although practitioners had an extremely negative
perception of the case law and some were also unhappy with the new statute, these
did lead to the reorganization and formalization of their practices. We can see
that judicial decisions taken in a specific, individual situation can change
collective practices and influence--or even overturn--public health strategies.
The respondents' intention to take parents' emotions into account suggests they
will find a common language to communicate with them. It is nonetheless necessary
to organize a nationwide debate about the objectives of fetal ultrasound.
PMID- 17028537
TI - [Gallbladder volvulus: Two cases].
AB - INTRODUCTION: Gallbladder volvulus remains a relatively rare disorder.
OBSERVATION: We report two cases, both in men older than 80 years and both
diagnosed during surgery. Both patients presented signs of peritonitis (one
generalized and the other localized) and severe sepsis. DISCUSSION: We review the
literature about gallbladder volvulus to analyze its incidence, etiology, and
clinical, radiologic and therapeutic characteristics.
PMID- 17028536
TI - [Adult idiopathic neutrophilic eccrine hidradenitis treated with colchicine].
AB - INTRODUCTION: Neutrophilic eccrine hidradenitis (NEH) is a rare disease belonging
to the group of neutrophilic dermatoses. It has a characteristic histopathologic
pattern, with necrosis of the eccrine glands and a local neutrophilic infiltrate.
It occurs mostly in patients receiving chemotherapy for acute myeloblastic
leukemia or, less frequently, another malignancy. Its occurrence in healthy
patients is rare. CASE REPORT: We report the case of a 56-year-old woman with no
remarkable medical history who developed an erythematous papular facial eruption.
Skin biopsy showed typical features of neutrophilic eccrine hidradenitis
including neutrophilic infiltrate. No cause was found. The patient was
successfully treated with colchicine. DISCUSSION: This case is particular because
NEH was not associated with malignant hematologic disease, solid cancer,
chemotherapy, fever or any other disease, after a follow-up of 22 months. Such
idiopathic NEH has been reported only rarely in adults. The second particularity
is the length of the eruption, which required colchicine treatment. Clinical
improvement occurred within 1 month. Because hematologic malignancies can in some
cases be preceded by neutrophilic dermatitis, clinical follow-up is recommended
in adults.
PMID- 17028538
TI - [Magnetic resonance imaging of endomyocardial fibrosis].
PMID- 17028539
TI - [The return of psychosurgery].
PMID- 17028540
TI - [New surgical techniques for brain tumors].
AB - During the past years, the development of new technologies and techniques has
been applied to brain tumor surgery, leading to decreased surgical morbidity and
increased efficiency. These techniques can be used to reduce the invasiveness of
the surgical approach (endoscopy, neuronavigation, robotics), to improve guidance
(stereotaxy, neuronavigation), to better identify the tumor limits
(neuronavigation, metabolic imaging, intra-operative MRI) or the functional areas
(functional imaging, electrophysiological functional mapping) to optimize
resection and to respect eloquent areas. This article reviews these techniques,
focusing on their respective principles, practical utility, impact and limits.
PMID- 17028541
TI - [How do the temporal lobes communicate in medial temporal lobe seizures?].
AB - INTRODUCTION: Spatial and temporal patterns of the spread of partial epileptic
seizures depend on the site from which they originate. Characterising seizure
propagation patterns may help to better define the seizure focus. In medial
temporal lobe epilepsies, seizure propagation to the contralateral temporal lobe
is especially studied. STATE OF THE ART: Intracranial EEG records permit more
precise definition of patterns of contralateral propagation in medial temporal
lobe epilepsies. Several pathways have been implicated, sometimes differently in
distinct studies, in propagation to the contralateral temporal lobe: the three
commissures (the corpus callosum, the ventral hippocampal commissure and the
anterior commissure, which link the temporal lobes) and an indirect circuit via
the frontal lobes. Delays measured for contralateral propagation of a seizure of
temporo-limbic origin vary significantly around a mean value of about 30 seconds.
This slow spread may depend in part on the relatively small size of human
commissural projections from the amygdalo-hippocampal formation, which largely
originate in the presubiculum. However, a larger commissural projection pathway
originates in the paralimbic medial temporal lobe and electrical stimulation of
the anterior perirhinal cortex can induce contralateral epileptic discharges with
delays as short as 100 ms (Adam et al., 2004). Thus, seizure activity emerging
from anterior paralimbic regions can propagate rapidly to the contralateral
medial temporal lobe via the anterior commissure. PERSPECTIVES: While the
propagation of medial temporal lobe seizures is still debated, further studies
are merited since the extent and speed of spread governs the electro-clinical
semiology of seizures and our ability to identify their initiation site.
CONCLUSIONS: We review anatomical (Demeter et al., 1990) and neurophysiological
(Wilson et al., 1990) data for a dual inter-temporal propagation of medial
temporal lobe seizures at different speeds and via different pathways.
PMID- 17028542
TI - [Unverricht-Lundborg disease (PME1)].
AB - Unverricht-Lundborg disease (ULD) is the purest and least severe type of
progressive myoclonus epilepsy (PME), and is not associated with progressive
cognitive deficit. Symptoms stabilize in adulthood, with a varying degree of
permanent, often severe handicap that is mostly due to myoclonus. The disorder
follows an autosomal recessive transmission pattern, with onset between 8 and 15
years years of age of generalized tonic-clonic or clonic-tonic-clonic seizures,
action myoclonus (massive or segmental), photosensitivity, and often ataxia.
Prevalence varies, it is highest in certain isolates (Finland, La Reunion Island)
and in region with higher levels of inbreeding (Maghreb). ULD is due to a deficit
in cystatin B (stefin B), but the mechanisms leading to the clinical symptoms are
not well understood. The causative gene, PME1, was identified in 1991 and
localized to chromosome 21q22.3. The mutations are mainly expansions of the
CCCCGCCCCGCG dodecamer, but less common point mutations were also found. A
variant has been recently reported in a Palestinian family, with localization on
chromosome 12. The diagnosis of ULD is made on the basis of family history, age
at onset, geographical and ethnic context, and on the typical features of
myoclonus and epilepsy, in the absence of cognitive and sensory deficits.
Neurophysiological evaluation yields interesting, but unspecific results. There
are no biological or pathological markers for ULD. Molecular analysis confirms
the diagnosis in most patients. Genetic testing for heterozygotes and even
prenatal diagnosis are possible, although seldom performed, if the mutation has
been identified. In spite of intensive research, ULD has yet to reveal all of its
secrets. It remains a quasi "idiopathic" type of PME, with limited progression.
Clinicians and patients are still waiting for an etiologically oriented
treatment, which should, ideally, be admnistered early in the course of the
disease, if possible before the onset of invalidating symptoms.
PMID- 17028543
TI - [CADASIL with minimal symptoms after 60 years].
AB - INTRODUCTION: CADASIL is a hereditary cerebral arteriopathy leading to
progressive disability and dementia usually observed at 60 years. OBSERVATION: We
report four patients aged>60 years with typical Notch3 mutations leading to
CADASIL who did not have dementia or disability. Three of them presented with
only transient neurological manifestations. MRI results showed extensive
hyperintense signals in the white-matter on T2-weighted images contrasting with
very few lacunar infarcts. CONCLUSION: These observations suggest that silent or
symptomatic infarcts, which were rare in the present cases may be responsible for
the clinical severity in this disorder.
PMID- 17028544
TI - [Stiff man syndrome: clinical forms, treatment and clinical course].
AB - INTRODUCTION: Stiff-Man syndrome (SMS) is a rare neurological disease first
described fifty years ago. There are several clinical forms, which are frequently
misdiagnosed. The aim of this study is to review three of the main clinical
forms. MATERIAL AND METHODS: Case reports concerning three women suffering from
different forms of SMS are presented, giving the main clinical features, their
associations with other diseases, and the biological and electrophysiological
findings. RESULTS: The first patient presented a symmetric axial muscle rigidity,
painful spasms and contractions of the trunk and limbs associated with anti-GAD
antibodies. The common form of SMS was diagnosed and the patient was improved by
intravenous immunoglobulin (IVIg). The second patient suffered from contractions
and spasms localized to the lower limbs. In this patient, anti-GAD antibodies
were absent. The Stiff-Leg syndrome was diagnosed and the patient was improved by
intrathecal baclofen. The third patient presented rigidity of limb and trunk
muscles associated with signs of encephalitis. In this patient, only anti
amphiphysin antibodies were present. The progressive encephalomyelitis with
rigidity was diagnosed and the patient was improved by IVIg associated with
corticosteroid. CONCLUSION: Identifying patients with SMS makes it possible to
propose appropriate medical management. There are several forms of the disease,
and the severity of the evolution differs in each case. Treatment with GABA-ergic
inhibitory drugs, IVIg and corticosteroid improve both the symptomatology and the
quality of life of these patients.
PMID- 17028546
TI - [Multiple gliomas: clinical studies and pathophysiological hypothesis].
AB - INTRODUCTION: Although a rare entity, multiple gliomas must be recognized and
distinguished from other causes of multiple brain lesions. METHODS: Clinical and
radiological features of 33 multiple gliomas were reviewed, including 20
synchronous cases and 13 metachronous cases. RESULTS: In 17 patients,
radiological features were highly suggestive of spread from a primary site
(multifocal gliomas). No apparent dissemination route was identified in the other
cases which were presumed to be multicentric gliomas. For nine patients (27
percent), a second neoplasia or cancer was found in first degree relatives
suggesting a genetic predisposition. Overall median survival was 79 weeks (64
weeks for glioblastomas). The age at onset was the main prognostic factor.
CONCLUSION: Multiple gliomas represent a heterogeneous entity, probably
corresponding to different mechanisms. In our group, survival was comparable to
unique glioma.
PMID- 17028545
TI - [Homocysteinemia and thrombophilic factors in unexplained decompression
sickness].
AB - INTRODUCTION: Decompression sickness with cerebral ischemic lesions occurs even
in divers who have not committed any technical error. This study sought to
determine whether an acquired or inborn thrombophilic factor might be involved.
METHODS: 44 divers with ischemic medullar lesions (36 men, 8 women, mean age
39.9+/-4.7 yr) were compared with 44 controls (34 men, 10 women, mean age 38.2+/
5.1 yr). Coagulation screening included proteins S, C, and thrombin III and
Factor VIII assays and circulating antibodies, Factor V Leiden, and mutation
G20210A in Factor II gene research. Total plasma homocysteine (Hcy), an
atherosclerosis factor (assayed by FPIA), folate and vitamin B12, (by
microbiology), the cofactors of its metabolism, were assayed, and subjects were
genotyped for mutation C677T on the MTHFR gene. RESULTS: Coagulation screening-
protein C, protein S, or antithrombin III deficit or mutation G20210A--was
negative in all divers. 3/44 divers were heterozygous for Factor V Leiden, 1/44
had IgG antiphospholipid antibodies (9p.cent). While not found in controls, these
percentages were not greater than those reported in the general population. 3/44
divers had elevated Factor VIII levels, but repeat assays on Day 2 were much
lower. 11/44 divers had a moderate increase in Hcy value (20p.cent): in 7 divers,
Hcy values were>15 micromol/L, and in 4 others>12, vs. 2.3p.cent of the controls;
2/11 had normal vitamin levels and 11 divers had folate or vitamin B12 deficiency
or both, vs 2.3p.cent controls with a vitamin B12 deficit (percentage
significantly different). 7/26 divers were homozygous for the C677T mutation,
i.e. 27p.cent vs 12p.cent of 98 healthy controls (laboratory technicians).
CONCLUSIONS: A high percentage of unexplained diving accident victims had
moderate HHC, a folate or vitamin B12 deficiency or both, that are easy to
detect, plus a genetic predisposition to HHC or to coagulation abnormality. Easy
to-perform homocysteine, vitamin B12, and folate assays might prove helpful for
primary prevention of diving accidents.
PMID- 17028547
TI - [Study of episodic memory in multiple sclerosis using the California Verbal
Learning Test: the data favour altered encoding].
AB - INTRODUCTION: Alteration of episodic memory is one of the main cognitive deficits
observed in MS patients. PATIENTS AND METHODS: We studied episodic memory in a
group of 71 MS patients (37 RR, 34 SP) with the California Verbal Learning test
(CVLT). Direct scores and calculated indices from CVLT performances were analyzed
in comparison with controls. RESULTS: We observed a deficit of episodic memory in
69 p.cent of patients. This deficit was related to an alteration of encoding and
retrieval processes. Despite SP-MS patients performances were constantly lower
than those of RR-MS patients no significant difference was observed between the
two groups. Significant correlation between the disease duration and CVLT
performances were observed for the whole group but not for RR- or SP-MS groups
separately, indicating that duration is more important than the phase of the
disease in the worsening of memory deficit.
PMID- 17028548
TI - [Type I glutaric aciduria: an unrecognized cause of progressive dystonia].
AB - INTRODUCTION: Glutaric acidemia type I is one of the least rare organic
acidemias. The number of diagnosed causes is however still low because the
presentation is variable and often confusing. The disease may sometimes have a
slowly progressive course. Typically, it presents in infancy, mimicking acute
encephalitis, leaving a previously healthy child severely handicapped with
generalized dystonia, spastic quadriplegia or choreoathetosis. Cerebral MRI shows
large CSF-containing spaces (sylvian fissures and anterior to the temporal lobes)
and basal ganglia abnormal signal. CASE REPORT: An eight year-old boy had begun
at 18 months with motor difficulties and abnormal posture of upper and lower left
limbs. When examined, he had generalized dystonia more pronounced at the left
side, severe dysarthria and tongue dystonia. IQ was normal. MRI showed high T2
signal in basal ganglia and enlarged CSF containing spaces. Urinary organic acids
chromatography confirmed glutaric acidemia type I. Two of his sisters deceased
before the age of two years with a clinical picture of fever, seizures and
hypotonia. Another sister had the same symptoms at the same age. She lived until
10 year with severe quadriplegia. COMMENTS: Our observation shows variability of
clinical picture and course of glutaric acidemia type I in the same kindred. We
propose systematic organic acides chromatography in all children with acute or
progressive dystonia with basal ganglia abnormalities on MRI. This seems an
imperative attitude because appropriate diet could slow the progression of the
illness.
PMID- 17028549
TI - [Chemotherapy treatment for anti-Hu paraneoplastic syndrome without active
malignancy].
AB - INTRODUCTION: Anti-Hu associated paraneoplastic neurological syndromes are rare
and characterized by poor prognosis. The research and treatment of a related
cancer, a small-cell lung cancer most of the time, remains the best therapeutic
strategy. CASE REPORT: We describe the clinical course of a paraneoplastic
subacute sensory neuronopathy associated with anti-Hu antibodies in a male smoker
treated by an early chemotherapy active against a small-cell lung cancer although
no tumor could be found at repeated evaluations. In spite of this treatment, the
neurological state deteriorated with the appearance of a cerebellar degeneration,
and limbic encephalitis which resulted in a loss of autonomy. A small-cell lung
cancer was found and treated 65 months after the onset of the neurological
symptoms. The treatment of the underlying malignancy, when it can be found, is
still considered as the optimal treatment for paraneoplastic neurological
syndromes. Although no tumor could be found, we treated our patient with an
empirical chemotherapy active against the most frequent malignancy associated to
anti-Hu syndrome in a smoker man, without any improvement. CONCLUSION: Active and
repeated research for a cancer related to an anti-Hu neurological syndrome and
its treatment are undispensable. For our patient without any identified cancer
empirical chemotherapy treatment was unable to stop neurological worsening. When
no tumor can be identified by conventional imaging techniques, an early FDG-PET
scan should be considered and then repeated if normal.
PMID- 17028550
TI - [Peroneal nerve schwannoma presenting with a peroneal palsy].
AB - Peroneal nerve injury in the lateral aspect of the knee is frequent, commonly
dominated by traumatic or compressive etiologies. Tumors, generally synovial
cysts, are exceptional causes. We report a case of a 70-year-old women referred
for assessment of peroneal palsy syndrome found to be related to peroneal
schwannoma in the lateral aspect of the knee. Schwannoma is the most frequent
peripheral nerve benign tumor. It is commonly limited to cranial and upper limb
nerves. Localization on the lower limbs (sciatic nerve) has been reported in 1
percent of cases. The peroneal nerve localizaton has not been reported to date.
We underline difficulties of diagnosis inherent to this particular localization.
PMID- 17028551
TI - [Idiopathic chronic dysautonomia: when should the diagnosis be made?].
AB - INTRODUCTION: Chronic autonomic disorders may complicate a wide range of
conditions which can be divided into secondary, due to specific diseases, and
primary, in which no cause has been determined. CASE REPORT: We report the case
of a 43-year-old woman, who presented a chronic autonomic failure, which had
begun by symptomatic orthostatic hypotension. Progressively, syncopes became
daily, causing considerable discomfort associated with other signs of sympathic
dysfunction: unilateral Horner's syndrome, diarrhea and hypohidrosis. The
autonomic involvement was confirmed by study of the cardiovascular responses to
tilt-up and electrophysiological autonomic testing. Etiologic search for a
chronic acquired neuropathy (diabetes, amyloidis, paraneoplastic) or an inherited
neuropathy was not conclusive. After five years, dysautonomic symptoms increased,
but remained isolated. The physical examination did not show other clinical
abnormalities such as cerebellar, pyramidal or extrapyramidal failure in favor of
a multiple system atrophy or Parkinson's disease. All these data suggest the
diagnosis of a primary autonomic failure. CONCLUSION: The diagnosis of primary
autonomic failure is difficult to make because it requires that all the
investigations in search of an etiology are negative and a long follow-up to be
sure that dysautonomic symptoms persist isolated after many years of progression.
PMID- 17028552
TI - [Rapid sensory motor neuropathy after gastric restriction surgery].
AB - INTRODUCTION: Central and peripheral neurological complications have been
described in association with bariatric surgery over the last 20 years. CASE
REPORT: A 40 year-old women developed a sensory motor neuropathy 3 months after a
gastric restriction operation followed by a 30 kilograms weight loss. No specific
vitamin or mineral deficiency was detected but she improved after multivitamin
and minerals supplementation. CONCLUSION: Acute or subacute neuropathy may
develop in 1 to 2p.cent of patients who undergo bariatric surgery. Its
pathogenesis is not very clear but the most commonly associated factors are rapid
weight loss and non-supplementation with vitamins and minerals post-operatively.
PMID- 17028553
TI - [Fatal giant cell arteritis with severe bilateral involvement of the vertebral
arteries].
AB - With steroid therapy, it is commonly considered that prognosis is good in giant
cell arteritis. However serious or even fatal complications may occur. Here we
report the case of a patient who developed fatal giant cell arteritis with severe
stenosis of both vertebral arteries and right carotid siphon. Several similar
cases have been reported in the literature. Initially diagnosis may be difficult
because neurological manifestations are intermittent and classical signs of giant
cell arteritis may be lacking. In such condition the reason of poor outcome is
unknown and therapy remains empiric.
PMID- 17028554
TI - [Neurological complications of Herpes zoster].
AB - INTRODUCTION: Herpes zoster is a disease which occurs secondary to the
reactivation of varicella-zoster virus (VZV). Its frequency is high in the
general population. STATE OF ART: Herpes zoster leads to numerous complications,
among which there were neurological peripheral or central lesions. Antiviral
treatment must be instituted, particularly if neurological complications develop,
as soon as possible. Corticosteroid therapy can be used, especially in Ramsay
Hunt syndrome or central nervous system involvement. CONCLUSION: Herpes-zoster is
a frequent disease which can lead to serious neurological complications. Early
treatment is necessary in order to improve functional outcome.
PMID- 17028555
TI - [THE SFN INTERNATIONAL MEETING Alzheimer's disease and dementia].
PMID- 17028556
TI - Transgenic mouse models for Alzheimer's disease: the role of GSK-3B in combined
amyloid and tau-pathology.
AB - Describing and understanding the pathological processes which devastate the brain
of Alzheimer's disease (AD) patients remains a major target for experimental
biology. We approached this problem by generating different types of single and
double transgenic mice that develop pathological hallmarks of AD. In APP-V717
mice, the progression from intracellular amyloid to diffuse and senile plaques
with vascular deposits, is preceded by early defects in cognition and LTP. In Tau
P301L mice, the morbid tauopathy with intracellular filaments, cause mortality
before age 1 year. Ageing APP-V717IxTau-P301L double tg mice (14-17 months) have
combined AD-like pathology in hippocampus and cortex consisting of amyloid
plaques and neurofibrillary tangles. Remarkably, while Tau-P301L mice die before
age 1 year, the APP-V717IxTau-P301L double tg mice survive much longer, which
correlates with alleviation of tauopathy in hindbrain, despite aggravation in
forebrain. This hypothesis is corroborated in Tau-P301LxGSK-3B double transgenic
mice, which have also an extended lifespan relative to Tau-P301L mice, that
correlates with reduction of brainstem tauopathy. At the same time, Tau-P301LxGSK
3B mice have dramatic forebrain tauopathy, with "tangles in almost all neurons",
although without hyper-phosphorylation of Tau. The data corroborate the
hypothesis that GSK-3B is the missing link between the amyloid and tau-pathology,
and position GSK-3B as prominent player in the pathogenesis in AD.
PMID- 17028557
TI - [From physiopathology to treatment of Alzheimer's disease].
AB - The natural and molecular history of familial or sporadic Alzheimer's disease
(AD) shows that APP (amyloid protein precursor) dysfunction is a consensual
central etiological factor in Alzheimer's disease (AD). This is demonstrated by
1) genetic defects involving APP gene or APP dysfunction (such as PS1 or PS2),
leading to the formation of neocortical amyloid plaques in familial AD; 2)
transgenic mice with these mutated genes that develop plaques; 3) both sporadic
and familial AD develop plaques. But two alternatives to explain the
physiopathology can be proposed: a gain of toxic function of AB peptide
(reflected by the amyloid cascade hypothesis) or a loss of function of APP, a
ubiquitous and well conserved protein with numerous possible neurotrophic
activities. On the other hand, AD is also characterized by another inescapable
degenerating process: tauopathy, an intraneuronal aggregation of tau proteins
into neurofibrillary tangles. Remarkably enough, progression of tauopathy in
neocortical areas fully explains the progressive clinical deficits of AD, from
memory loss to aphasia, apraxia, agnosia. Also one has to bare in mind that most
demented patients and most dementing neurodegenerative disorders have a
tauopathy. From that, it is concluded that APP an Tau are solid therapeutic
targets. But if we know that APP and Tau dysfunctions interact to boost
neurodegeneration in AD, we still do no know what are the intraneuronal signaling
pathways to activate or to inhibit to stop the degenerating process. There are
many hypotheses and many possible approaches: the inhibition of toxicity of
plaque, of AB protofibrils, or of AB oligomers inside or outside the neuron,
using vaccination or ligands (Alzhemed). On the other hand, modulation of
secretases that cleave APP by inhibiting those involved in the amyloidogenic
pathway or by stimulating those of the non-amyloidogenic pathway, is a major
route of research. Also modulation of kinases or phosphatases possibly involved
in the aggregation of tau is also investigated. Because animal models are not
perfectly relevant, at the end of the long and costly pathway of drug discovery,
therapeutic trials are the only way to test these different hypotheses.
PMID- 17028558
TI - [Neuropsychological markers for the diagnosis of Alzheimer's disease].
AB - Better knowledge of the preclinical phase of Alzheimer's disease and of the
symptomatic pre-dementia stage designated "mild cognitive impairment" will
require considerable progress in our understanding of neuropsychological
processes. The results of studies suggest that impaired performance in memory
tests may serve as a marker for Alzheimer's disease. The best current predictors
include stringent tests of episodic memory and recognition tests. The early
stages of Alzheimer's disease also seem to involve subtle deficits in semantic
memory and attentional processes. Face recognition and denomination seem to be
useful tools. Greater accuracy and precision in the transitional zone between
healthy aging and the first manifestations of Alzheimer's disease will require
work combining data on neuropsychological profiles and neuroimaging.
PMID- 17028559
TI - [Nosology of dementias: the neuropathologist's point of view].
AB - The diagnosis of degenerative dementias heavily relies on the identification of
neuronal or glial inclusions. Tauopathy is probably the largest group including
Alzheimer and Pick disease, mutation of the tau gene, progressive supranuclear
palsy, corticobasal degeneration, and argyrophilic grain disease. Lewy bodies,
when numerous in the cerebral cortex, are usually associated with the cognitive
deficit of Parkinson disease dementia or of dementia with Lewy bodies--both
conditions being distinguished by clinical information. The inclusions of the
dentate gyrus, only labeled by anti-ubiquitin antibodies, isolate a subgroup of
fronto-temporal dementia (FTDu), sometimes familial and sometimes associated with
amyotrophic lateral sclerosis. Mutations of the progranulin gene have been
recently discovered among a significant proportion of these patients. Neuronal
Intermediate Filament Inclusion Disease (NIFID) is a rare, apparently sporadic
dementia, characterized by the presence of large inclusions in the cell body of
many neurons. These inclusions react with antibodies directed against
neurofilaments or against other intermediate filaments (such as alpha
internexin). The diagnostic value of some of these inclusions allowing the
classification of the degenerative dementias has been discussed. The link between
the inclusions and the pathogenetic mechanism is indeed probably variable. It
should however be stressed that whenever their composition has been elucidated,
the inclusions have given important clues to the pathogenesis of the disease in
which they had been found.
PMID- 17028560
TI - [Alzheimer's disease and human memory].
AB - Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to
a detailed analysis into the framework of cognitive neuropsychology which aimed
at describing the deficits of very specific processes. Beyond their clinical
interest, these studies contributed to the modelisation of human memory thanks to
the characterization of different memory systems and their relationships. The
first part of this paper gives an overview of the memory deficits in Alzheimer's
disease and insists on particular cognitive phenomena. Hence, several examples
are developed in the domains of semantic memory (such as hyperpriming and
hypopriming effects) and autobiographical memory. Recent results highlight the
existence of severe autobiographical amnesia observed in all neurodegenerative
diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's
disease (showing that remote memories are better preserved than recent ones),
reverse gradient in semantic dementia and no clear gradient in the frontal
variant of frontotemporal dementia. The second part of this article presents
advances in cognitive neuroscience searching to disclose the cerebral substrates
of these cognitive deficits in Alzheimer's disease. The studies using functional
imaging techniques are the most informative regarding this problematic. While
showing the dysfunctions of an extended network, they emphasize the selectivity
of cerebral damages that are at the root of very specific cognitive dysfunctions,
coming close in that way to the conceptions of cognitive neuropsychology. These
neuroimaging studies unravel the existence of compensatory mechanisms, which
until recently were clearly missing in the literature on neurodegenerative
diseases. These different researches lead to a wide conception of human memory,
not just limited to simple instrumental processes (encoding, storage, retrieval),
but necessarily covering models of identity and continuity of the subject, which
interact in a dynamic way with eminently changing memory representations.
PMID- 17028561
TI - Functional MRI in the early detection of dementias.
AB - Functional MRI is a non-invasive imaging technology that can illuminate regional
brain activity during the performance of a task, such as a memory paradigm, or at
rest. fMRI data can be acquired during a session in which MRI data is also
acquired to measure grey and white matter regional brain structure, and these
measures can be analyzed together to investigate the relationships between
altered regional brain function, structure, and cognitive task performance in
neurologic illness. Data will be reviewed on the application of fMRI to the early
detection of physiologic abnormalities associated with neurodegenerative diseases
that cause dementia, and to differential diagnosis of dementias. Recent fMRI work
will also be reviewed on the identification of abnormalities in regional brain
function prior to dementia, the use of these measures to predict cognitive
decline, and their application in investigations of alterations in regional brain
networks that subserve cognitive function. Finally, the use of fMRI as a
biomarker in clinical trials of putative neurotherapeutics for dementias will be
discussed.
PMID- 17028562
TI - [Brain profile of hypometabolism in early Alzheimer's disease: relationships with
cognitive deficits and atrophy].
AB - While accurate and early prediction of patients that will develop Alzheimer's
disease (AD) in the near future is urgently needed, the amnestic Mild Cognitive
Impairment (MCI) state is of particular interest since it most conveniently
represents the pre-dementia stage of AD. Consistently, the profile of brain
functional alteration constantly evidenced in resting-state SPECT and PET studies
is similar to that observed in mild AD, mainly involving the posterior cingulate
and temporo-parietal regions. While the former is a characteristic feature of
MCI, since it is present in each patient at this stage, the latter seems
specifically associated with the future conversion to AD. Moreover, right temporo
parietal hypometabolism has been found to be the best predictor of subsequent
global cognitive decline, over and above neuropsychological and MRI volumetric
measurements. This review also presents a discussion on the relationships between
the brain profile of hypometabolism on the one hand, and cognitive impairment as
well as cerebral structural alterations on the other. Thus, firstly, while
functional impairment in the posterior cingulate region seems to be associated
with deficits in retrieval of episodic memories in MCI, the relationship between
right temporo-parietal hypometabolism and cognitive impairment is still obscure.
However, several arguments point to its relation with visuo-spatial deficits,
which are often associated with future conversion to AD. Secondly, the
discordance between brain areas of major functional changes, and those of highest
structural alterations, leads to some relevant questions about the relations
between both pathological manifestations and their underlying mechanisms. More
specifically, additional hypometabolism-inducing factors could occur in areas of
highest hypometabolism compared to atrophy, i.e. mainly in posterior associative
cortical regions, leading to genuine functional perturbation in early AD before
the development of real atrophy and perhaps of disease as well. By contrast, the
hippocampus is the main site of atrophy while its functional alteration is still
debated, suggesting that compensation/protective mechanisms probably specifically
occur in this structure to maintain a high level of metabolism relative to its
structural alteration.
PMID- 17028563
TI - [Update on the genetics of X-linked mental retardation].
AB - Mutations in X-linked genes are likely to account for the observation that more
males than females are affected with mental retardation. Causative mutations have
been identified in both syndromic XLMR and in the genetically heterogeneous non
syndromic forms of XLMR, without a clear clinical phenotype other than cognitive
deficit. Progress in genome analysis and the establishment of large
collaborations between clinical and molecular research teams, especially the
European XLMR consortium, have led to the identification of 20 non-syndromic XLMR
genes and 25 syndromic XLMR genes. Given the extensive heterogeneity of non
syndromic XLMR, different strategies are used for the identification of new
genes: linkage analysis, studies of balanced chromosomal rearrangements (X
autosome translocations, microdeletions) and candidate genes strategies by
mutation screening in regions of the X chromosome known to be involved in
neuronal development and function. Delineating the monogenic causes of XLMR and
their molecular and cellular consequences will provide insight into the
mechanisms that are required for normal development of cognitive function in
humans. Non syndromic XLMR proteins include 5 distinct classes: transmembrane
receptors, small GTPases effectors or regulators, enzymes and translational
regulators.
PMID- 17028564
TI - [Contribution of ecological evaluation of executive disorders in multiple
sclerosis].
AB - INTRODUCTION: Multiple sclerosis (MS) is a major cause of neurological disability
among young adults. The cognitive disorders are the second cause of alteration of
quality of life after physical handicap and are often responsible for loss of
social-occupational adaptability. The prevalence of cognitive disorders is 40 to
65%. The alteration of executive functions predominates whereas instrumental
functions are generally preserved. The assessment of these disorders is often
underestimated by the usual battery of neuropsychological tests. However, the
link between psychometric results and executive difficulties of daily life is
uncertain. OBJECTIVES: To evaluate the sensitivity of an ecological test compared
to standard psychometric tests in assessment of executive disorders in MS.
METHODS: Twenty subjects with clinically definite MS were matched for age, sex
and pre-morbid intellectual level with control subjects. A battery of
neuropsychological and ecological tests was applied to all subjects. The
performances on these tests formed a global score of executive function (SFE).
The "paper and pencil" multiple errands test was used as the ecological test to
examine planning and goal-oriented behavior. We also assessed fatigue and
depression with the Fatigue Severity Scale and the Beck Depression Inventory.
RESULTS: There was no significant differences between MS patients and controls in
neuropsychological executive tests, except for verbal fluencies (p=0.01). The
performances were significantly decreased in the MS group for the multiple
errands test (p=0.01). 75% of MS subjects have a pathological score for this
test. There was a significant link between the performances with this test and
SFE (p=0.009). CONCLUSIONS: Executive disorders are underestimated in MS.
However, we suggest that an ecological approach is more reliable than standard
neuropsychological tests to estimate the cognitive difficulties in daily life in
MS subjects. The results of our study favor further research to ascertain the
usefulness of ecological assessment in MS.
PMID- 17028565
TI - [Cognitive impairment and quality of life in multiple sclerosis patients].
AB - INTRODUCTION: Cognitive disorders may bias perception of quality-of-life in
patients with multiple sclerosis (MS). METHODS: Neuropsychological tests (WAIS
vocabulary, Grober and Buschke, Stroop, WCST, WAIS-similitude, fluency,
Hamilton's depression scale) along with a French health-related quality of life
self questionnaire for MS patients (the SEP59) were performed by 117 MS patients
with a minor cognitive impairment (Mini Mental State over 24) in order to explore
the links between quality of life perception and cognitive functioning. RESULTS:
Main Component Analysis and correlation analysis showed that cognitive impairment
produced an overrating of the self perception of quality of life. Threshold
analysis, splitting patients between the most and the less cognitively impaired,
confirmed this relationship. CONCLUSION: The level of cognitive functioning must
be considered with caution when analyzing health-related quality of MS patients.
PMID- 17028566
TI - [Idiopathic acute transverse myelitis: application of new diagnosis criteria to
17 patients].
AB - INTRODUCTION: Idiopathic Acute Transverse Myelitis (ATM) is an inflammatory and
immune-mediated disorder, distinct from infectious ATM, ATM of systemic lupus
erythematosus or Sjogren's syndrome, and medullary manifestation of multiple
sclerosis. Prognosis is not well-known. OBJECTIVE: To evaluate clinical,
paraclinical and pronognosis data in patients selected with new diagnosis
criteria, classically described in idiopathic ATM. METHODS: Seventeen patients
with diagnosis criteria were retrospectively (1996-2005) studied. A telephone
investigation was conducted in 2005 to obtained data on the clinical course.
RESULTS: Seven men and 10 women, ranging in age from 15 to 75 years (mean: 39.8
years) met these new criteria. Our study showed that epidemiological and clinical
findings as well as laboratory results were in agreement with those presented in
the literature. Conversely, prognosis was better since 76p.cent of the patients
could walk without assistance. The clinical presentation of some of our patients
and/or their progression towards other multifocal inflammatory disorders,
suggests there might be links between ATM, neuromyelitis optica (NMO) and Acute
Dissemined Encephalomyelitis (ADEM). CONCLUSION: Patients with idiopathic ATM,
selected with new criteria, have a rather good prognosis. ATM seems to be part of
a continuum of neuroimmunologic disorders including NMO or ADEM although reasons
explaining distinct focal disorders remain unclear.
PMID- 17028567
TI - [Late onset forms of myasthenia gravis. Comparison with early-onset myasthenia
gravis].
AB - INTRODUCTION: The incidence of myasthenia gravis appears to be increasing in
elderly but few studies have been devoted to late onset myasthenia gravis.
PATIENTS AND METHODS: We retrospectively compared myasthenic patients with an age
at onset above or below 35 years which were observed in two departments of
Neurology from 1980 to 2002. RESULTS: 81 cases were included, 28 of which were
late onset myasthenia gravis. The two populations were similar in terms of sex
ratio, clinical symptoms, course of the disease and therapeutic response. There
was a trend for older patients to present more frequently at onset with dysphagia
and axial or proximal involvement, and to have extra-ocular symptoms more
quickly. Antibodies against acetylcholine receptor and striated muscle were
statistically more frequent in elder patients. CONCLUSIONS: A late onset is not a
factor of poor prognosis in myasthenia gravis and older patients must be treated
in the same way than younger ones.
PMID- 17028568
TI - [Finnish amyloid polyneuropathy in a French patient].
AB - INTRODUCTION: Finnish amyloid variety is a rare familial amiloidosis
polyneuropathy essentially observed in Finland. It concerns about six hundred
people in the world in which five hundred reside in Finland. OBSERVATION: We
report a case of a 58-year-old French woman with a 10-year history of lattice
cornea dystrophy. She consulted in January 2004 for impaired swallowing, facial
paralysis principally of the right superior territory and symptoms of arthritis
which had developed a few months earlier. Observation revealed facial cutis laxa,
tongue amyotrophy and some fasciculation. Electroneuromyography showed chronic
neurogenic involvement of the facial muscles. Limbs and the sympathetic neuronal
system were free of involvement. Pathological examination revealed areas of peri
vascular amiloid deposits. Molecular biology confirmed the diagnosis of Finnish
amiloidosis: substitution of aspartic acid by tyrosine in the 187 codon in the
9th chromosome (gelsoline gene). This mutation has been previously found in
Denmark and the Czech Republic. CONCLUSION: Finnish amiloidosis is a familial
polyneuropathy characterized by an association of cornea lattice dystrophy, cutis
laxa and a chronic neurogenic involvement of the cranial nerves. Two mutations
are known. Life expectancy is not affected, but quality of life is altered.
PMID- 17028569
TI - [Diffuse lower motor neuron disease in a carcinomatous meningitis].
AB - INTRODUCTION: Between 4 and 15% of solid cancers are associated with
carcinomatous meningitis ant its unfavorable prognosis. The clinical presentation
of neoplastic meningitis typically associates cerebral signs, cranial nerve
involvement, and medullary or radicular symptoms. OBSERVATION: We report a case
of a 58-year-old woman, with a history of breast cancer in remission since 8
years, who presented an acute paraparesia and a pure motor deficit of the left
arm. This diffuse lower motor neuron disease was the inaugural sign of
carcinomatous meningitis. CONCLUSION: The diagnosis of cacinomatous meningitis is
based on medullar MRI and lumbar puncture. In same cases, clinical signs are
limited to a pure diffuse lower motor neuron disease.
PMID- 17028570
TI - [Ischemic, an uncommon complication of Biermer disease (pernicious anemia)].
AB - INTRODUCTION: Stroke in a young adult justifies an extensive etiologic workup.
OBSERVATION: We present a 44-year-old women victim of a frontal ischemic stroke.
Extensive evaluation was normal, except for high plasma level of homocysteine in
the context of pernicious anemia, otherwise asymptomatic. DISCUSSION:
Hyperhomocysteinemia is a known marker, and probably risk factor for stroke,
fostering atherosclerosis and thrombosis. It can be found among individuals
suffering from homocystinuria, in individuals homozygous for the MHTFR T allele
but also when there is deficiency of vitamin B12 or folic acid. Although it is
very seldom ascribed, pernicious anemia would be a cause of stroke, possibly
though hyperhomocysteinemia.
PMID- 17028571
TI - [Reversible acute postpartum cerebral angiopathy].
AB - Acute cerebral angiopathy is a rare neuro-vascular complication in postpartum. In
this setting, the implication of vasoconstrictive drugs used for lactation or
deliverance hemorrhage inhibition has been established. This review aimed 1) to
describe, epidemiologic, clinical and diagnostic features of this pathological
condition. 2) To put in perspective this condition within the scope of
neurovascular clinical syndrome of pregnancy.
PMID- 17028572
TI - [Continuous subcutaneous infusion of apomorphine for the treatment of Parkinson's
disease].
AB - Apomorphine administered by subcutaneous infusion has been used efficiently in
parkinsonian patients to treat severe motor fluctuations and levodopa-induced
dyskinesias. Despite increasing evidence of its efficacy and its relative safety,
apomorphine infusion therapy is still underused. This article reviews
pharmacokinetic properties, efficacy, tolerability and indications of apomorphine
infusion in Parkinson's disease.
PMID- 17028573
TI - Itch/AIP4 mediates Deltex degradation through the formation of K29-linked
polyubiquitin chains.
AB - Deltex (DTX) and AIP4 are the human orthologues of the Drosophila deltex and
Suppressor of deltex, which have been genetically described as being
antagonistically involved in the Notch signalling pathway. Both genes encode E3
ubiquitin ligases of the RING (Really interesting new gene)-H2 and HECT
(Homologous to E6AP carboxyl terminus) families, respectively. In an attempt to
understand the molecular basis of their genetic interactions, we studied the
relationship between DTX and AIP4 in the absence of activation of the Notch
pathway. We show here that both molecules interact and partially colocalize to
endocytic vesicles, and that AIP4 targets DTX for lysosomal degradation.
Furthermore, AIP4-generated polyubiquitin chains are mainly conjugated through
lysine 29 of ubiquitin in vivo, indicating a link between this type of chain and
lysosomal degradation.
PMID- 17028574
TI - Acetylation is important for MyoD function in adult mice.
AB - Acetylation is a post-translational modification that influences the activity of
numerous proteins in vitro. Among them, the myogenic transcription factor MyoD
shows an increased transcriptional activity in vitro when acetylated on two
lysines (K): lysines 99 and 102. Here, we have investigated the biological
relevance of this acetylation in vivo. Using specific antibodies, we show that
endogenous MyoD is acetylated on lysines 99 and 102 in myoblasts. Moreover, we
show the functional importance of acetylation in live animals by using a mutant
of MyoD in which lysines 99 and 102 were replaced by arginines (R). Knock-in
embryos homozygous for the MyoD(R99,102) allele expressed slightly reduced levels
of MyoD but developed normally. However, the knock-in homozygous adult mice
showed a phenotype that was almost identical to that of MyoD-knockout animals,
including delayed muscle regeneration in vivo and an increased number of
myoblasts but with reduced differentiation potential in vitro. Together, these
results show the importance of MyoD acetylation for adult myogenesis.
PMID- 17028576
TI - Magnetic imaging of a supercooling glass transition in a weakly disordered
ferromagnet.
AB - Spin glasses are founded in the frustration and randomness of microscopic
magnetic interactions. They are non-ergodic systems where replica symmetry is
broken. Although magnetic glassy behaviour has been observed in many colossal
magnetoresistive manganites, there is no consensus that they are spin glasses.
Here, an intriguing glass transition in (La,Pr,Ca)MnO3 is imaged using a variable
temperature magnetic force microscope. In contrast to the speculated spin-glass
picture, our results show that the observed static magnetic configuration seen
below the glass-transition temperature arises from the cooperative freezing of
the first-order antiferromagnetic (charge ordered) to ferromagnetic transition.
Our data also suggest that accommodation strain is important in the kinetics of
the phase transition. This cooperative freezing idea has been applied to
structural glasses including window glasses and supercooled liquids, and may be
applicable across many systems to any first-order phase transition occurring on a
complex free-energy landscape.
PMID- 17028575
TI - Dengue-virus-infected dendritic cells trigger vascular leakage through
metalloproteinase overproduction.
AB - Dengue virus (DV) is an important re-emerging arthropod-borne virus of global
significance. The defining characteristic of DV infection-associated pathology is
haemorrhagic fever, which often leads to a fatal shock-like syndrome (DHF/DSS)
owing to an increase in vascular endothelial permeability. Here, we show, in a
viral dose-dependent manner, that DV-infected immature dendritic cells
overproduce soluble gelatinolytic matrix metalloproteinase (MMP)-9-and to a
lesser extent MMP-2-which enhances endothelial permeability, but which are
reduced by specific inhibitors and a neutralizing anti-MMP-9 antibody. This
permeability was associated with a loss of expression of the platelet endothelial
adhesion molecule 1 (PECAM-1) and vascular endothelium (VE)-cadherin cell
adhesion molecules and redistribution of F-actin fibres. These in vitro
observations were confirmed in an in vivo vascular-leakage mouse model. These
results provide a molecular basis for DHF/DSS that could be a basis for a general
model of haemorrhagic fever-inducing viruses, and identify a new therapeutic
approach for the treatment of viral-induced vascular leakage by specifically
targeting gelatinolytic metalloproteases.
PMID- 17028577
TI - Exciton polarizability in semiconductor nanocrystals.
AB - The response of charge to externally applied electric fields is an important
basic property of any material system, as well as one critical for many
applications. Here, we examine the behaviour and dynamics of charges fully
confined on the nanometre length scale. This is accomplished using CdSe
nanocrystals of controlled radius (1-2.5 nm) as prototype quantum systems.
Individual electron-hole pairs are created at room temperature within these
structures by photoexcitation and are probed by terahertz (THz) electromagnetic
pulses. The electronic response is found to be instantaneous even for THz
frequencies, in contrast to the behaviour reported in related measurements for
larger nanocrystals and nanocrystal assemblies. The measured polarizability of an
electron-hole pair (exciton) amounts to approximately 10(4) A(3) and scales
approximately as the fourth power of the nanocrystal radius. This size dependence
and the instantaneous response reflect the presence of well-separated electronic
energy levels induced in the system by strong quantum-confinement effects.
PMID- 17028578
TI - Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce
irreversible cellular senescence.
AB - The p16(INK4a) cyclin-dependent kinase inhibitor has a key role in establishing
stable G1 cell-cycle arrest through activating the retinoblastoma (Rb) tumour
suppressor protein pRb in cellular senescence. Here, we show that the p16(INK4a)
/Rb-pathway also cooperates with mitogenic signals to induce elevated
intracellular levels of reactive oxygen species (ROS), thereby activating protein
kinase Cdelta (PKCdelta) in human senescent cells. Importantly, once activated by
ROS, PKCdelta promotes further generation of ROS, thus establishing a positive
feedback loop to sustain ROS-PKCdelta signalling. Sustained activation of ROS
PKCdelta signalling irreversibly blocks cytokinesis, at least partly through
reducing the level of WARTS (also known as LATS1), a mitotic exit network (MEN)
kinase required for cytokinesis, in human senescent cells. This irreversible
cytokinetic block is likely to act as a second barrier to cellular
immortalization ensuring stable cell-cycle arrest in human senescent cells. These
results uncover an unexpected role for the p16(INK4a)-Rb pathway and provide a
new insight into how senescent cell-cycle arrest is enforced in human cells.
PMID- 17028579
TI - A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated
exocytosis.
AB - Fusion of vesicles into target membranes during many types of regulated
exocytosis requires both SNARE-complex proteins and fusogenic lipids, such as
phosphatidic acid. Mitochondrial fusion is less well understood but distinct, as
it is mediated instead by the protein Mitofusin (Mfn). Here, we identify an
ancestral member of the phospholipase D (PLD) superfamily of lipid-modifying
enzymes that is required for mitochondrial fusion. Mitochondrial PLD (MitoPLD)
targets to the external face of mitochondria and promotes trans-mitochondrial
membrane adherence in a Mfn-dependent manner by hydrolysing cardiolipin to
generate phosphatidic acid. These findings reveal that although mitochondrial
fusion and regulated exocytic fusion are mediated by distinct sets of protein
machinery, the underlying processes are unexpectedly linked by the generation of
a common fusogenic lipid. Moreover, our findings suggest a novel basis for the
mitochondrial fragmentation observed during apoptosis.
PMID- 17028580
TI - Probing cell-division phenotype space and Polo-like kinase function using small
molecules.
AB - Cell-permeable small molecules that inhibit their targets on fast timescales are
powerful probes of cell-division mechanisms. Such inhibitors have been identified
using phenotype-based screens with chemical libraries. However, the
characteristics of compound libraries needed to effectively span cell-division
phenotype space, to find probes that target different mechanisms, are not known.
Here we show that a small collection of 100 diaminopyrimidines (DAPs) yields a
range of cell-division phenotypes, including changes in spindle geometry,
chromosome positioning and mitotic index. Monopolar mitotic spindles are induced
by four inhibitors, including one that targets Polo-like kinases (Plks),
evolutionarily conserved serine/threonine kinases. Using chemical inhibitors and
high-resolution live-cell microscopy, we found that Plk activity is needed for
the assembly and maintenance of bipolar mitotic spindles. Plk inhibition
destabilizes kinetochore microtubules while stabilizing other spindle
microtubules, leading to monopolar spindles. Further testing of compounds based
on 'privileged scaffolds', such as the DAP scaffold, could lead to new cell
division probes and antimitotic agents.
PMID- 17028581
TI - Inhibitors of Polo-like kinase reveal roles in spindle-pole maintenance.
AB - Polo-like kinases (Plks) have several functions in mitotic progression and are
upregulated in many tumor types. Small-molecule Plk inhibitors would be valuable
as tools for studying Plk biology and for developing antitumor agents. Guided by
homology modeling of the Plk1 kinase domain, we have discovered a chemical series
that shows potent and selective Plk1 inhibition. The effects of one such
optimized benzthiazole N-oxide, cyclapolin 1 (1), on purified centrosomes
indicate that Plks are required to generate MPM2 epitopes, recruit gamma-tubulin
and enable nucleation of microtubules. The compound can also promote loss of
centrosome integrity and microtubule nucleating ability apparently through
increased accessibility of protein phosphatases. We show that treatment of living
S2 cells with cyclapolin 1 leads to collapsed spindles, in contrast to the
metaphase-arrested bipolar spindles observed after RNAi. This different response
to protein depletion and protein inhibition may have significance in the
development of antitumor agents.
PMID- 17028582
TI - Discrimination learning induced by training with identical stimuli.
AB - Sensory stimuli become easier to detect or distinguish with practice. It is
generally assumed that the task-relevant stimulus dimension becomes increasingly
more salient as a result of attentively performing the task at a level that is
neither too easy nor too difficult. However, here we show improved auditory
frequency discrimination following training with physically identical tones that
were impossible to discriminate. We also show that learning transfers across tone
frequencies and across modalities: training on a silent visuospatial computer
game improved thresholds on the auditory discrimination task. We suggest that
three processes are necessary for optimal perceptual learning: sensitization
through exposure to the stimulus, modality- and dimension-specific attention, and
general arousal.
PMID- 17028583
TI - Limited transfer of learning between unimanual and bimanual skills within the
same limb.
AB - Although a limb's motion appears to be similar across unimanual and bimanual
movements, here we demonstrate partial, but not complete, transfer of learning
across these behavioral contexts, hidden learning that remains intact (but
invisible) until the original context is again encountered, and the ability to
associate two conflicting force fields simultaneously, one with each context.
These results suggest partial, but not complete, overlap in the learning
processes involved in the acquisition of unimanual and bimanual skills.
PMID- 17028584
TI - An allocentric rather than perceptual deficit in patient D.F.
AB - The perception/action model states that vision for perception and vision for
action are processed in separate pathways. This model was inspired by
observations in patient D.F. who seemed unable to use vision for perceptual tasks
while retaining 'normal' visuomotor capacity. I found that D.F.'s performance is
preserved in perceptual and visuomotor tasks when the required spatial
information is hand-centered and impaired when the information is object
centered.
PMID- 17028585
TI - Force field effects on cerebellar Purkinje cell discharge with implications for
internal models.
AB - The cerebellum has been hypothesized to provide internal models for limb movement
control. If the cerebellum is the site of an inverse dynamics model, then
cerebellar neural activity should signal limb dynamics and be coupled to arm
muscle activity. To address this, we recorded from 166 task-related Purkinje
cells in two monkeys performing circular manual tracking under varying viscous
and elastic loads. Hand forces and arm muscle activity increased with the load,
and their spatial tuning differed markedly between the viscous and elastic
fields. In contrast, the simple spike firing of 91.0% of the Purkinje cells was
not significantly modulated by the force nor was their spatial tuning affected.
For the 15 cells with a significant force effect, changes were small and
isolated. These results do not support the hypothesis that Purkinje cells
represent the output of an inverse dynamics model of the arm. Instead these
neurons provide a kinematic representation of arm movements.
PMID- 17028586
TI - Ongoing eye movements constrain visual perception.
AB - Eye movements markedly change the pattern of retinal stimulation. To maintain
stable vision, the brain possesses a variety of mechanisms that compensate for
the retinal consequences of eye movements. However, eye movements may also be
important for resolving the ambiguities often posed by visual inputs, because
motor commands contain additional spatial information that is necessarily absent
from retinal signals. To test this possibility, we used a perceptually ambiguous
stimulus composed of four line segments, consistent with a shape whose vertices
were occluded. In a passive condition, subjects fixated a spot while the shape
translated along a certain trajectory. In several active conditions, the spot,
occluder and shape translated such that when subjects tracked the spot, they
experienced the same retinal stimulus as during fixation. We found that eye
movements significantly promoted perceptual coherence compared to fixation. These
results indicate that eye movement information constrains the perceptual
interpretation of visual inputs.
PMID- 17028587
TI - Disruption of diacylglycerol metabolism impairs the induction of T cell anergy.
AB - Anergic T cells have altered diacylglycerol metabolism, but whether that altered
metabolism has a causative function in the induction of T cell anergy is not
apparent. To test the importance of diacylglycerol metabolism in T cell anergy,
we manipulated diacylglycerol kinases (DGKs), which are enzymes that terminate
diacylglycerol-dependent signaling. Overexpression of DGK-alpha resulted in a
defect in T cell receptor signaling that is characteristic of anergy. We
generated DGK-alpha-deficient mice and found that DGK-alpha-deficient T cells had
more diacylglycerol-dependent T cell receptor signaling. In vivo anergy induction
was impaired in DGK-alpha-deficient mice. When stimulated in anergy-producing
conditions, T cells lacking DGK-alpha or DGK-zeta proliferated and produced
interleukin 2. Pharmacological inhibition of DGK-alpha activity in DGK-zeta
deficient T cells that received an anergizing stimulus proliferated similarly to
wild-type T cells that received CD28 costimulation and prevented anergy
induction. Our findings suggest that regulation of diacylglycerol metabolism is
critical in determining whether activation or anergy ensues after T cell receptor
stimulation.
PMID- 17028588
TI - RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling
and thymocyte development.
AB - RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase
family with unknown physiological function. Here we demonstrate that Rhoh-/- mice
have impaired T cell receptor (TCR)-mediated thymocyte selection and maturation,
resulting in T cell deficiency. RhoH deficiency resulted in defective CD3zeta
phosphorylation, impaired translocation of the signaling molecule Zap70 to the
immunological synapse and reduced activation of Zap70-mediated signaling in
thymic and peripheral T cells. Proteomic analyses demonstrated that RhoH is a
component of TCR signaling and is required for recruitment of Zap70 to the TCR
through interaction with RhoH noncanonical immunoreceptor tyrosine-based
activation motifs (ITAMs). In vivo reconstitution studies also demonstrated that
RhoH function depends on phosphorylation of the RhoH ITAMs. These findings
suggest that RhoH is a critical regulator of thymocyte development and TCR
signaling by mediating recruitment and activation of Zap70.
PMID- 17028589
TI - T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase
alpha.
AB - T cell anergy has been correlated with defective signaling by the GTPase Ras, but
causal and mechanistic data linking defective Ras activity with T cell anergy are
lacking. Here we used adenoviral transduction to genetically manipulate
nonproliferating T cells and show that active Ras restored interleukin 2
production and mitogen-activated protein kinase signaling in T cells that were
made anergic in vitro or in vivo. Diacylglycerol kinases (DGKs), which negatively
regulate Ras activity, were upregulated in anergic T cells, and a DGK inhibitor
restored interleukin 2 production in anergic T cells. Both anergy and DGK-alpha
overexpression were associated with defective translocation of the Ras guanine
nucleotide-exchange factor RasGRP1 to the plasma membrane. Our data support a
causal function for excess DGK activity and defective Ras signaling in T cell
anergy.
PMID- 17028590
TI - RNA polymerase II C-terminal domain mediates regulation of alternative splicing
by SRp20.
AB - Previous studies have linked the C-terminal domain (CTD) of RNA polymerase II
(pol II) with cotranscriptional precursor messenger RNA processing, but little is
known about the CTD's function in regulating alternative splicing. We have
examined this function using alpha-amanitin-resistant pol II CTD mutants and
fibronectin reporter minigenes. We found that the CTD is required for the
inhibitory action of the serine/arginine-rich (SR) protein SRp20 on the inclusion
of a fibronectin cassette exon in the mature mRNA. CTD phosphorylation controls
transcription elongation, which is a major contributor to alternative splicing
regulation. However, the effect of SRp20 is still observed when transcription
elongation is reduced. These results suggest that the CTD promotes exon skipping
by recruiting SRp20 and that this contributes independently of elongation to the
transcriptional control of alternative splicing.
PMID- 17028591
TI - Amino acid residues in Rag1 crucial for DNA hairpin formation.
AB - The Rag proteins carry out V(D)J recombination through a process mechanistically
similar to cut-and-paste transposition. Specifically, Rag complexes form DNA
hairpins through direct transesterification, using a catalytic Asp-Asp-Glu (DDE)
triad in Rag1. How is sufficient DNA distortion introduced to allow hairpin
formation? We hypothesized that, like certain transposases, the Rag proteins
might use aromatic amino acid residues to stabilize a flipped-out base. Through
in vivo and in vitro experiments and structural predictions, we identified
residues in Rag1 crucial for hairpin formation. One of these, a conserved
tryptophan (Trp893), probably participates in base-stacking interactions near the
cleavage site, as do Trp298, Trp265 and Trp319 in the Tn5, Tn10 and Hermes
transposases, respectively. Other residues surrounding the catalytic glutamate
(YKEFRK) may share functional similarities with the YREK motif in IS4 family
transposases.
PMID- 17028594
TI - Principles of micro-RNA production and maturation.
AB - Micro-RNAs (miRNAs) are a class of approximately 22-nucleotide non-coding RNAs
expressed in multicellular organisms. They are first transcribed in a similar
manner to pre-mRNAs. The transcripts then go through a series of processing
steps, including endonucleolytic cleavage, nuclear export and a strand selection
procedure, to yield the single-stranded mature miRNA products. The transcription
and processing of miRNAs determines the abundance and the sequence of mature
miRNAs and has important implications for the function of miRNAs.
PMID- 17028595
TI - Principles and effects of microRNA-mediated post-transcriptional gene regulation.
AB - MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of
many key biological processes. Recent advances in understanding the mechanism of
RNA interference and miRNA-mediated mechanisms shed light on major principals of
the formation of the regulatory complex and provide models to explain how these
small regulatory RNA species interfere with gene expression and how they
influence the translational status of the transcriptome.
PMID- 17028596
TI - MicroRNAs and the hallmarks of cancer.
AB - It has become clear that particular microRNAs (miRNAs) function either as tumour
suppressors or oncogenes, whose loss or overexpression, respectively, has
diagnostic and prognostic significance. In several cases, miRNAs have been shown
to affect target genes that are involved in the control of cell proliferation and
apoptosis. However, malignant tumours display additional traits beyond the
acquisition of enhanced growth potential and decreased cell death. Malignant
disease is associated with altered tumour-host interactions leading to sustained
angiogenesis and the ability to invade and metastasize. It is possible that
miRNAs may act as master regulators of these aspects of tumour biology.
Bioinformatic analysis of putative miRNA binding sites has indicated several
novel potential gene targets of cancer-associated miRNAs that function in aspects
of cell adhesion, neovascularization and tissue invasion. Among others, we
speculate that miRNAs may find new roles in the regulation of E-cadherin,
integrin alphavbeta3, hypoxia-inducible factor-1alpha, syndecan-1, lysyl oxidase,
adamalysin metalloproteinase-17, tissue inhibitors of metalloproteinase-3, c-Met
and CXCR-4 that underpin the tissue architectural changes associated with
malignancy.
PMID- 17028597
TI - miRNAs and apoptosis: RNAs to die for.
AB - MicroRNAs (miRNAs) are small non-coding RNAs of about 18-24 nucleotides in length
that negatively regulate gene expression. Discovered only recently, it has become
clear that they are involved in many biological processes such as developmental
timing, differentiation and cell death. Data that connect miRNAs to various kinds
of diseases, particularly cancer, are accumulating. miRNAs can influence cancer
development in many ways, including the regulation of cell proliferation, cell
transformation, and cell death. In this review, we focus on miRNAs that have been
shown to play a role in the regulation of apoptosis. We first describe in detail
how Drosophila has been utilized as a model organism to connect several miRNAs
with the cell death machinery. We discuss the genetic approaches that led to the
identification of those miRNAs and subsequent work that helped to establish their
function. In the second part of the review article, we focus on the involvement
of miRNAs in apoptosis regulation in mammals. Intriguingly, many of the miRNAs
that regulate apoptosis have been shown to affect cancer development. In the end,
we discuss a virally encoded miRNA that influences the cell death response in the
mammalian host cell. In summary, the data gathered over the recent years clearly
show the potential and important role of miRNAs to regulate apoptosis at various
levels and in several organisms.
PMID- 17028598
TI - A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes.
AB - The known classes of genes that function as tumor suppressors and oncogenes have
recently been expanded to include the microRNA (miRNA) family of regulatory
molecules. miRNAs negatively regulate the stability and translation of target
messenger RNAs (mRNA) and have been implicated in diverse processes such as
cellular differentiation, cell-cycle control and apoptosis. Examination of tumor
specific miRNA expression profiles has revealed widespread dysregulation of these
molecules in diverse cancers. Although studies addressing their role in cancer
pathogenesis are at an early stage, it is apparent that loss- or gain-of-function
of specific miRNAs contributes to cellular transformation and tumorigenesis. The
available evidence clearly demonstrates that these molecules are intertwined with
cellular pathways regulated by classical oncogenes and tumor suppressors such as
MYC, RAS and p53. Incorporation of miRNA regulation into current models of
molecular cancer pathogenesis will be essential to achieve a complete
understanding of this group of diseases.
PMID- 17028599
TI - Tumour-related microRNAs functions in Caenorhabditis elegans.
AB - Altering cell proliferation and differentiation are usually key events leading to
cancer. As originally demonstrated by Sydney Brenner in 1960s, the nematode
Caenorhabditis elegans represents an animal model of choice to study mechanisms
important to maintain proper cellular behaviour. This round worm has helped to
elucidate components as well as new cellular pathways required for animal
development. Among them, the discovery of the programmed cell death and non
coding RNAs (microRNAs) controlling gene expression are two remarkable examples.
Recently, two studies have demonstrated, once again, that using C. elegans can
help gathering insights on cellular mechanisms leading to tumour formation. Two
microRNAs, miR-84 and miR-61, control the expression of the oncogene orthologues
Ras and Vav indicating their capacity to act as tumour suppressors. These
observations demonstrate that uncovering the function of microRNAs is important
to increase our understanding of cancer.
PMID- 17028600
TI - MicroRNAs and chromosomal abnormalities in cancer cells.
AB - Over the past five decades, a plethora of nonrandom chromosomal abnormalities
have been consistently reported in malignant cells facilitating the
identification of cancer-associated protein coding oncogenes and tumor
suppressors. The genetic dissection of hot spots for chromosomal abnormalities in
the age of the sequenced human genome resulted in the discovery that microRNA
(miRNA) genes, encoding for a class of small noncoding RNAs, frequently resides
in such genomic regions. The combination of nonrandom chromosomal abnormalities
and other types of genetic alterations or epigenetic events contribute to
downregulation or overexpression of miRNAs. The consequent abnormal expression of
miRNAs affect cell cycle, survival and differentiation programs and selective
targeting of these noncoding genes could provide novel therapeutic options for
killing the malignant cells.
PMID- 17028601
TI - Viruses, microRNAs and cancer.
AB - Viruses represent one of the main factors that cause normal cells to proliferate
and to become malignant: up to 15% of all human cancers are associated with
single or multiple virus infections, and several viruses have been recognized as
causal agents of specific types of cancer. Viruses have evolved many strategies
to prevent infected cells from becoming apoptotic and to evade the innate and
adaptive immune responses of their hosts. The recent discovery that Epstein-Barr
virus and other herpesviruses produce their own sets of micro (mi)RNAs brings an
additional layer of complexity in this ongoing host-virus arms race and changes
our initial views of the antiviral roles of RNA silencing in plants and insects.
It seems that, rather than being inhibited by this process, many mammalian
viruses can usurp or divert the host RNA silencing machinery to their advantage.
Viral-encoded miRNAs can act both in cis, to ensure accurate expression of viral
genomes, and in trans, to modify the expression of host transcripts. Here, we
review the current knowledge on viral miRNAs and discuss how mammalian viruses
can also perturb host miRNA expression. Those recent findings provide new
insights into the role of viruses and miRNAs in cancer development.
PMID- 17028602
TI - Implications of micro-RNA profiling for cancer diagnosis.
AB - Micro-RNAs (miRNAs) are a large class of small non-coding RNAs that regulate
protein expression in eucaryotic cells. Initially believed to be unique to the
nematode Caenorhabditis elegans, miRNAs are now recognized to be important gene
regulatory elements in multicellular organisms and have been implicated in a
variety of disease processes, including cancer. Advances in expression
technologies have facilitated the high-throughput analysis of small RNAs,
identifying novel miRNAs and showing that these genes may be aberrantly expressed
in various human tumors. These studies suggest that miRNA expression profiling
can be correlated with disease pathogenesis and prognosis, and may ultimately be
useful in the management of human cancer.
PMID- 17028622
TI - Alveolar hemorrhage following allogeneic hematopoietic cell transplantation using
reduced-intensity conditioning.
AB - Allogeneic hematopoietic cell transplantation (HCT) using reduced-intensity
conditioning (RIC) has lower morbidity and mortality compared to transplantation
using myeloablative conditioning (MAC). The syndrome of alveolar hemorrhage, a
life-threatening pulmonary complication of HCT, has not been well described after
RIC HCT. We reviewed prospectively collected data on 206 RIC and 1112 MAC HCT
performed between 1995 and 2004 to study the impact of conditioning regimen on
the clinical features and outcome of alveolar hemorrhage. Alveolar hemorrhage
occurred in 18 RIC HCT recipients (cumulative incidence 8% (95% confidence
intervals (CI), 5-11%)) and 85 MAC HCT recipients (cumulative incidence 7% (95%
CI, 6-8%), P = 0.56). The clinical presentation of hemorrhage in both cohorts was
similar. Survival at 60 days from the onset of hemorrhage was 28% (95% CI, 7-49%)
for RIC group compared to 26% (95% CI, 17-35%) after MAC HCT (P = 0.56). Reducing
the intensity of preparative regimen does not protect against post transplant
alveolar hemorrhage. Alveolar hemorrhage occurring after RIC or MAC HCT has
similar incidence, clinical presentation, and associated high mortality.
PMID- 17028623
TI - Reduced-intensity unrelated cord blood transplantation for treatment of
metastatic renal cell carcinoma: first evidence of cord-blood-versus-solid-tumor
effect.
AB - We report a 69-year-old man with cytokine-resistant metastatic renal cell
carcinoma treated with reduced-intensity unrelated cord blood transplantation.
The patient achieved durable donor engraftment with minimal graft-versus-host
disease. The patient showed regression of metastatic disease, providing the first
evidence of a graft-versus-tumor effect on a solid tumor resulting from cord
blood graft.
PMID- 17028625
TI - [You should not tolerate].
PMID- 17028624
TI - Outcome of adult umbilical cord blood transplant patients admitted to a medical
intensive care unit.
AB - Umbilical cord blood transplant (UCBT) has emerged as an alternate source of stem
cells for transplantation in patients with hematologic malignancies. However,
outcomes of adult UCBT patients requiring ICU admission remain unknown. In order
to identify predictors of ICU transfer and mortality in UCBT patients, the course
and outcome of all adult (> or = 16 years old) patients who underwent UCBT
between 1 January 1998 and 31 December 2003 at University Hospitals of Cleveland
were analyzed. Forty-four patients underwent UCBT during the study period and 25
(57%) required ICU transfer. Use of a myeloablative preparative regimen was a
significant predictor of ICU transfer (P = 0.03). An infusion of higher numbers
of nucleated cells was protective from ICU transfer (P = 0.05). For those
patients transferred to the ICU, mortality was 72%. The univariate predictors of
mortality, at the time of ICU admission were a high APACHE III score (P =
0.0004), use of vasopressors (P = 0.03), and a low platelet count (P = 0.03). We
conclude that transfer of UCBT patients to an ICU may be predicted by their
preparative regimen, while ICU mortality may be predicted by physiologic
parameters upon admission.
PMID- 17028626
TI - [Vaccination--the story about that's what did not happen].
PMID- 17028627
TI - [Possibilities to help in amyotrophic lateral sclerosis].
PMID- 17028628
TI - [Pregnancy, birth and neurologic disease].
PMID- 17028629
TI - [Epilepsy and pregnancy--drug use, seizure control, and complications].
AB - BACKGROUND: There is insufficient knowledge about the effect of epilepsy and
epilepsy treatment on pregnancy, and vice versa. The European Registry of
Antiepileptic drugs and Pregnancy (EURAP) was therefore established in 1999. We
here present the results from the Norwegian part of the study, with emphasis on
attack control, use of antiepileptics and folate, presence of status epilepticus,
attacks in connection with birth and complications in the pregnancy. MATERIAL AND
METHOD: The study is prospective and observational. The women are offered 5
consultations, 3 during pregnancy and 2 after birth. RESULTS: As of September
2005, 296 pregnancies in 263 Norwegian women were included. In 220 pregnancies
(74 %), the women were treated with a single antiepileptic drug, most often
carbamazepine. In 187 pregnancies (63 %), the women were seizure free. In those
with seizures, 17 % had an increase in seizure frequency during pregnancy and 15
% had a decrease. Convulsive status epilepticus associated with delivery occurred
in 1 % of the women and seizures associated with the delivery in 2.7 %. The
consequences for the mother and the child were not as serious as previously
reported. The frequency of complications during pregnancy and the sectio rate did
not differ significantly from the average population. INTERPRETATION: Most women
with epilepsy go through pregnancy and delivery without complications.
Specialists should only follow up those with a suboptimal seizure control. The
slightly increased teratogenic risk can be reduced by giving these women extra
folate before the conception.
PMID- 17028630
TI - [Sexual abuse of prepubertal children].
AB - BACKGROUND: During the last 15 years, a considerable change has taken place
regarding the understanding of anatomical and microbiological anogenital findings
in children. At the end of the 1980s, abnormal findings were described in more
than 50 % of allegedly abused children. Today such findings are described in 5 %.
An important consequence of this change is that absence of abnormal findings
should never be used to exclude abuse, not even abuse with anogenital
penetration. The main reason for this change is increased knowledge about normal
variation and healing after injury, as well as an improvement in standardisation
of terminology. MATERIAL AND METHODS: This paper is based on relevant literature
published on this topic. RESULTS AND CONCLUSIONS: During this period, several
findings have been reclassified from abnormal to normal or non-specific. Examples
of such findings are anal dilatation, large and gaping hymenal opening and narrow
hymenal brim. Some of the previously reported cases of anogenital scarring are
probably mis-classified normal structures. Research-based international
classification scales are now established in order to aid the physician in
diagnosing sexual abuse, and these are revised on a regular basis. It is
currently common to classify medical findings into three main categories;
normal/unspecific findings, indeterminate findings and diagnostic findings.
PMID- 17028631
TI - [Risk factors for sudden cardiac death related to the long QT syndrome].
AB - BACKGROUND: Long QT syndrome is a rare condition. The syndrome is characterised
by a prolonged QT-interval corrected for heart rate (QTc). The typical clinical
presentation is the occurrence of syncope or cardiac arrest in young and
otherwise healthy individuals. Cardiac events can be precipitated by
environmental factors and use of certain drugs. The purpose of the present study
is to provide guidelines regarding risk factors that may worsen the syndrome,
based on available literature. MATERIAL AND METHODS: PubMed was searched for all
literature in English from 1966 through 2004 on the Long QT syndrome. The
articles and their literature references were examined. Additional information
was achieved from experienced colleagues and from some key sites on the internet.
RESULTS: The symptoms of the Long QT syndrome are tachycardia, syncope or cardiac
arrest, often related to psychological or physical stress in young, usually
healthy individuals. The syndrome can be inherited or acquired and is commonly
caused by mutations in the potassium channel or by lack of inactivation of the
sodium channels. The most common causes of acquired conditions are electrolyte
abnormalities, intracranial disease, dietary deficiencies, myocardial infarction,
dilated cardiomyopathy, mitral valve prolapse, bradycardia, severe malnutrition
among anorexic patients and the use of medication. INTERPRETATION: It is
important to have knowledge about the Long QT Syndrome. The treatment is
primarily to remove potential risk factors and medically to give beta-blockers or
insert pacemakers or cardiac defibrillators.
PMID- 17028632
TI - [Quality of life of patients with amyotrophic lateral sclerosis].
AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) leads to loss of important body
functions, a huge need for assistance and is associated with a low quality of
life (QoL). We have investigated QoL in ALS patients treated by a
multidisciplinary ALS team, and to which degree this team met the patients'
needs. MATERIAL AND METHODS: The patients' health-related QoL was measured by use
of SF-36, and content with the treatment offered by the team was evaluated
through a structured interview of 14 ALS patients at the Neurological Department
at Ulleval University Hospital, Oslo, Norway. RESULTS: The patients reported low
scores for physical QoL, but mental QoL was close to that of the general
population. The patients were generally content with the treatment given by the
ALS team. They were most content with the practical help given to organize their
homes and the accessibility of different members of the team. They were least
content with the psychological help and the information given to their relatives.
Content with treatment was not correlated with self-perceived QoL or with
physical disability. INTERPRETATION: Our findings suggest that the patients are
content with the ALS team, but that their psychological reactions and information
to relatives are not handled well enough. Most ALS patients treated by the ALS
team experience their life as meaningful, regardless of their degree of
neurological dysfunction.
PMID- 17028633
TI - [Communication aids in amyotrophic lateral sclerosis].
AB - BACKGROUND: Many patients with amyotrophic lateral sclerosis lose the ability to
speak, and in late-stage disease also the ability to communicate through
gestures. Social isolation is one of the greatest burdens of this disease.
Implementation of alternative and augmentative communication can increase the
quality of life even in advanced disease. MATERIALS AND METHODS: We have
systematically recorded alternative and augmentative communication aids given to
patients treated by the amyotrophic lateral sclerosis team at Ulleval University
Hospital from 1998 to 2005, and evaluated the results in the light of current
literature. RESULTS: 62 out of 92 patients received alternative and augmentative
communication aids. Alternative and augmentative communication was more often
used by female than male patients (p = 0.01). Except for two who developed
dementia, all patients were able to express basic needs until the terminal stage
of the disease. INTERPRETATION: Most patients retain enough mobility of head and
eyes to use communication aids until the terminal stage. Physicians must know the
possibilities and limitations of assisted and augmentative communication in order
to give appropriate treatment and information, also concerning life-sustaining
treatment.
PMID- 17028634
TI - [Echinacea spp. (coneflower) and upper respiratory tract infections].
PMID- 17028636
TI - [The Norwegian vaccination program].
AB - Development of vaccines has in many ways been the art of the possible, using
current knowledge about infections and microbes to devise new products. The aim
of every vaccination is to prevent disease, but use of vaccines within
vaccination programs is usually targeted not only to protect the individual, but
also to changing the epidemiology of the disease. Several new vaccines will
become available during the next decade, but the vaccination program will
probably not be dramatically changed. Increased knowledge about the immune system
might, in a longer time perspective, make it possible to rebuild a vaccination
program on a new basis. Immunisations can perhaps be used for targeting the
immune system in ways that still give protection against the specific infections,
but in addition lead to better health through general protection against
diseases, less allergy and less autoimmune diseases than we have today.
PMID- 17028635
TI - [The cow, the boy and the lymph node--immunological principles for vaccines].
AB - Vaccines stimulate the immune system by activating professional antigenpresenting
cells, such as dendritic cells. Dendritic cells express a number of pattern
recognition receptors (PRR) on their surface, receptors that recognize structures
on viruses and bacteria. These receptors stimulate maturation of dendritic cells
that thereafter migrate to regional lymph nodes where they present vaccine
antigens to T-cells. PRR- ligands of the vaccine are decisive for the efficacy of
the immune response. This article discusses cellular principles and mechanisms
for vaccine responses; including antigen processing and presentation, T-cell
circulation, Th1-, Th2- and CTL T-cell responses and T-B cell cooperation, as
well as primary and secondary T and B cell responses and lymphocyte recirculation
and homing.
PMID- 17028637
TI - [Adverse events after vaccination].
AB - When the diseases we try to prevent through vaccination are rare, we tend to
focus more on the associated risks. Vaccination has led to unfortunate
consequences, mainly due to production failure and inadequate control in earlier
years. The requirements for vaccine control are now so rigorous that the risk for
such occurrences is close to zero. Local and mild systemic reactions to vaccines
are rather common, and are usually well known and described in detail when a
vaccine is licensed. Some vaccine reactions are however so rare that they only
will be discovered through surveillance after the vaccine has become available
for routine use. Suspicion of adverse events will now normally arise through the
official notification systems for adverse events. Large epidemiological studies
are often necessary to decide whether there is a causal relationship or only a
coincidence. Recording of adverse events following vaccination and transparency
about their existence, are important issues in the work to maintain the
credibility of vaccines.
PMID- 17028638
TI - [Disability insurance--are drug addicts discriminated?].
PMID- 17028639
TI - [Gender and language in primary health care].
PMID- 17028640
TI - [Genefec--one more time].
PMID- 17028642
TI - [Latin--keep the culture!].
PMID- 17028644
TI - [Generic preparations--undocumented effects?].
PMID- 17028645
TI - [Gaza--a comment].
PMID- 17028646
TI - [Politics in the Tidsskrift].
PMID- 17028647
TI - [Summer-juicy from Mads Gilbert].
PMID- 17028650
TI - [Unexploded bombs in Gaza].
PMID- 17028653
TI - [Surgical treatment og obstetric fistulas].
PMID- 17028656
TI - The effect of Johne's disease on production traits in Romney, Merino and Merino x
Romney-cross ewes.
AB - AIM: To quantify the effects of clinical Johne's disease on the performance of
Romney, Merino and Merino x Romney-cross ewes. METHODS: The performance of ewes
was compared using eight birth cohorts (1971-1978). Merino and Merino-cross
genotypes included New Zealand Merino and Australian Superfine Merino sources.
Intensive monitoring of Johne's disease was undertaken over the production years
1975-1982. Positive diagnostic evidence of Johne's disease was established post
mortem from lesions of granulomatous enteritis associated with high numbers of
acid-fast bacilli. Over years, data on a total of 2,341 Romney ewes and 1,292
Merino and Merino x Romney-cross ewes were recorded, consisting of annual records
of liveweight (LWT), greasy fleece weight (FWT), number of lambs born per ewe per
year (NLB), and lifetime productivity of ewes. RESULTS: A total of 82 (3.5%)
Romney ewes and 62 (4.8%) Merino and Merino x Romney-cross ewes were diagnosed
with clinical Johne's disease over the 8-year monitoring period, equivalent to
0.9% and 1.2% annual cases for these breeds, respectively, of the ewes present at
mating. The percentage of clinical cases (p<0.04) and the age at death from
Johne's disease (p<0.02) were lower for Romneys than for Superfine Merinos. The
mean age of death from Johne's disease was 3.41 (standard error (SE) 0.06) years,
lower than the mean disposal age from the flock of 5.03 (SE 0.02) years for
clinically normal ewes (p<0.001). In their final year of production, ewes with
clinical Johne's disease had lower LWT by 5.3 kg (10.5% of the mean; p<0.001),
lower annual FWT by 0.54 (SE 0.10) kg (14.2%; p<0.001), fewer NLB by 0.15 (SE
0.07) lambs (13%; p<0.05), and lower litter weaning weights by 3.6 (SE 1.3) kg
(15%; p<0.01) compared with clinically normal ewes. The size of the production
losses associated with Johne's disease depended on the age to which ewes
survived. Considering all production years of ewes (up to 8 years), the total
weight of lambs weaned by ewes with clinical Johne's disease was 30.9 (SE 3.4) kg
lower (46%; p<0.001) than the total from clinically normal ewes. CONCLUSIONS:
Clinical Johne's disease led to significant losses in LWT, FWT, NLB, and in the
lifetime production of ewes, amounting overall to a 46% reduction in productivity
(p<0.001). CLINICAL RELEVANCE: Productivity losses from clinical cases of Johne's
disease would be of considerable economic importance in flocks with a high
incidence of the disease. The lack of good diagnostic tests for Johne's disease
in the live animal, and the lack of active surveillance programmes, has made it
difficult to establish the true prevalence of Johne's disease in sheep flocks in
New Zealand, and its economic consequences.
PMID- 17028657
TI - Segmental axonopathy of Merino sheep in New Zealand.
AB - AIM: To investigate an axonopathy of Merino sheep that caused progressive
hindlimb ataxia and slight to moderate paresis, with the purpose of understanding
its pathogenesis. METHODS: Tissues were fixed in buffered paraformaldehyde or
paraformaldehyde and glutaraldehyde, processed into wax and epoxy resin,
respectively, and examined by light and electron microscopy. Fresh frozen spinal
cord and trigeminal nerve roots were subjected to homogenisation, centrifugation
and two-dimensional electrophoresis. Selected protein spots were identified using
matrix-assisted laser desorption ionisation (MALDI) mass spectrometry. RESULTS.
By light microscopy, there were large pale foamy spheroidal axonal swellings
affecting peripheral as well as central axons. By electron microscopy, these were
shown to contain many membrane-bound vesicles. The main abnormalities in
expressed proteins involved cytoskeletal elements and myosin heavy chain, the
latter interpreted as associated with the molecular motor myosin Va. CONCLUSIONS:
The disorder is the same as that described in Merinos in Australia as segmental
axonopathy, and believed to have an inherited aetiology. The lesions and protein
changes indicate abnormalities of the cytoskeleton, its relationship with the
myelin sheath, and myosin Va molecular motor. The consequence appears to be
abnormal axonal transport and inability to maintain the integrity of axons and
their myelin sheaths.
PMID- 17028658
TI - The effect of fertility control on the transmission of bovine tuberculosis in
wild brushtail possums.
AB - AIM: To determine the effect of fertility control on the rate of transmission of
bovine tuberculosis (Tb), caused by Mycobacterium bovis, in brushtail possums
(Trichosurus vulpecula). METHODS: At two study sites with a history of Tb
infection in the resident possum population, a sample of adult male and female
possums (n=50), determined by palpation to be Tb-free, was surgically sterilised
by gonadectomy. A sample of untreated Tb-free male and female possums (n=54)
served as controls. Each study site was trapped every 2 months over a 3-year
period, and the Tb status of the individuals in the trial assessed. At the
conclusion of the trial, all remaining experimental individuals were killed,
necropsied and examined for characteristic lesions typical of Tb. The rate of
transmission of Tb infection was estimated using the incidence of tuberculous
cases in the experimental animals and comparing it between sites, sex and
sterilisation treatment. RESULTS: Sterilisation by gonadectomy resulted in a
reduction in the rate of transmission of Tb in male possums by 53%, but a
corresponding increase in sterilised females for reasons that are still unclear.
However, this interaction was statistically weak (p=0.10). When the sexes were
combined, there was no overall effect of sterilisation on the rate of
transmission of Tb (p=0.43). Sterility treatment notwithstanding, there was a
highly significant difference in the rate of transmission between the sexes
(p=0.01), being almost one order of magnitude higher in untreated males compared
with untreated females. CONCLUSIONS: Although lacking strong statistical support,
these results suggest that fertility control that targets endocrine control of
fertility may provide some additional benefits for disease control over that
achieved by reductions in population density, by reducing the rate of
transmission of M. bovis in male possums. However, additional studies are needed
to confirm the validity of these results. The large difference in the rate of
transmission of M. bovis in untreated males compared with untreated females
suggests that transmission of Tb among males may be an important driver of the
dynamics of Tb infection in possums.
PMID- 17028659
TI - Oral vaccination of brushtail possums with BCG: Investigation into factors that
may influence vaccine efficacy and determination of duration of protection.
AB - AIMS: To determine factors that may influence the efficacy of an oral pelleted
vaccine containing Mycobacterium bovis bacille Calmette-Guerin (BCG) to induce
protection of brushtail possums against tuberculosis. To determine the duration
of protective immunity following oral administration of BCG. METHODS: In Study 1,
a group of possums (n=7) was immunised by feeding 10 pellets containing dead
Pasteur BCG, followed 15 weeks later with a single pellet of live Pasteur BCG. At
that time, four other groups of possums (n=7 per group) were given a single
pellet of live Pasteur BCG orally, a single pellet of live Danish BCG orally, 10
pellets of live Pasteur BCG orally, or a subcutaneous injection of live Pasteur
BCG. For the oral pelleted vaccines, BCG was formulated into a lipid matrix, and
each pellet contained approximately 107 colony forming units (cfu) of BCG, while
the vaccine injected subcutaneously contained 106 cfu of BCG. A sixth, non
vaccinated, group (n=7) served as a control. All possums were challenged by the
aerosol route with a low dose of virulent M. bovis 7 weeks after vaccination, and
killed 7-8 weeks after challenge. Protection against challenge with M. bovis was
assessed from pathological and bacteriological findings. In Study 2, lipid
formulated live Danish BCG was administered orally to three groups of possums (10
11 per group), and these possums were challenged with virulent M. bovis 8, 29 or
54 weeks later. The possums were killed 7 weeks after challenge, to assess
protection in comparison to a non-vaccinated group. RESULTS: The results from
Study 1 showed that vaccine efficacy was not adversely affected by feeding dead
BCG prior to live BCG. Feeding 10 vaccine pellets induced a level of protection
similar to feeding a single pellet. Protection was similar when feeding possums a
single pellet containing the Pasteur or Danish strains of BCG. All vaccinated
groups had significantly reduced pathological changes or bacterial counts when
compared to the non-vaccinated group. In Study 2, oral administration of Danish
BCG induced protection against challenge with M. bovis, which persisted for at
least 54 weeks after vaccination. Some protection was observed in possums
challenged 54 weeks after vaccination, but this protection was significantly less
than that observed in groups vaccinated 29 or 8 weeks prior to challenge. There
was a strong relationship between the proportion of animals producing positive
lymphocyte proliferation responses to M. bovis antigens and protection against
challenge with M. bovis. CONCLUSIONS: Factors considered potentially capable of
interfering with vaccination, including feeding dead BCG to possums prior to
feeding live BCG, feeding multiple doses of BCG at one time, and changing strains
of BCG, were shown not to interfere with the acquisition of protective immune
responses in possums. Protection against tuberculosis was undiminished up to 29
weeks after vaccination with BCG administered orally. It is concluded that
vaccination of possums by feeding pellets containing BCG is a robust and
efficient approach to enhance the resistance of these animals to tuberculosis.
PMID- 17028660
TI - A possible predisposition to dilated cardiomyopathy in Huntaway dogs.
AB - AIM: To compare the prevalence of dilated cardiomyopathy (DCM) in New Zealand
Huntaway dogs with the prevalence of DCM in other breeds of dog. METHODS: The
necropsy database at Massey University was used to identify cases of DCM
diagnosed between January 1999 and March 2006. Dogs were considered to have DCM
if echocardiographic, gross necropsy, or histological findings were consistent
with this diagnosis. The prevalence in Huntaways was then compared with the
prevalence observed in all breeds of dog, as well as the prevalence observed in
large breeds of dog. RESULTS: Twelve dogs were identified with DCM. One was
diagnosed using echocardiography, while the other 11 were diagnosed by gross
necropsy examination. The gross diagnosis of DCM was confirmed histologically in
6/11 dogs. The prevalence of DCM in Huntaways was significantly higher than the
prevalence seen in all breeds of dog (p=0.008), and the prevalence in large
breeds of dog (p=0.025). All four Huntaways diagnosed with DCM were male, and had
an average age of 4 years. Three dogs presented with symptoms attributable to
impaired heart function while one presented with symptoms of chronic renal
failure. The duration of clinical symptoms prior to presentation ranged between 1
day and 3 weeks. CONCLUSIONS: The results of this study suggest that Huntaways
may be predisposed to the development of DCM. Although the increased prevalence
in this breed was significant, only small numbers of affected Huntaways were
identified, and additional cases are required to confirm these preliminary
findings. CLINICAL RELEVANCE: Huntaways are the most common working dog in New
Zealand. The premature loss of a working dog is expected to have a significant
economic impact on farmers. Further investigation of DCM in Huntaways may allow
measures to reduce the prevalence in this breed.
PMID- 17028661
TI - The effect on creatinine kinase activity of freezing plasma from healthy foals.
AB - AIM: To assess the stability of creatine kinase (CK) activity in plasma collected
from healthy foals and frozen at -20 degrees C for up to 12 weeks. METHODS:
Samples of venous blood drawn from 25 foals were analysed for CK activity soon
after collection, and again after 1 and 12 weeks of freezing at -20 degrees C.
RESULTS: CK activity decreased (p<0.001) between Week 0 and Week 1 and between
Week 0 and Week 12. CONCLUSIONS AND CLINICAL RELEVANCE: Decreases in CK activity
were statistically significant but clinically insignificant.
PMID- 17028662
TI - Lesions in sheep following administration of a vaccine of a Freund's complete
adjuvant nature used in the control of ovine paratuberculosis.
AB - CASE HISTORIES: Occurrences of adverse reactions in seven sheep flocks in
Australia following vaccination against paratuberculosis where veterinary
attention was requested are reviewed. All cases occurred within the 3-year period
following commencement of use of a vaccine of a Freund's complete adjuvant
nature, at a time when approximately six million doses of vaccine had been
administered. CLINICAL FINDINGS: In the first case, 26/58 (45%) Merino sheep
vaccinated as adults had palpable tissue reactions at or near the site of
vaccination; enlarged prescapular lymph nodes were palpated in 17 (29%), and nine
(16%) sheep had both palpable lesions at the site of vaccination and enlarged
prescapular lymph nodes. The reactions included caseous nodules up to 5.5 cm in
diameter. In the other cases, fistulating or granulomatous wounds were
occasionally found at the recommended site of injection behind the ear, and
myiasis was rare. Occurrences of inappropriate choice of injection site were
recorded, including injection into the axilla of two Merino rams, and lesions in
the tissues of the maxilla and nose of almost 50% of 350 Border Leicester lambs.
Four outbreaks of progressive paralysis due to injection into cervical
musculature were reported, described as "OJD staggers" by producers. DIAGNOSIS:
Granulomatous cellulitis and lymphadenitis associated with oil droplets typical
of "oil granulomata". Injection of vaccine into the dorsal cervical area resulted
in progressive paralysis due to myonecrosis and suspected granulomatous
leptomeningitis. CLINICAL RELEVANCE AND CONCLUSIONS: Although lesions at and near
the site of injection are common, adverse reactions to vaccination were rare and
included mortality from cervical spinal injection, production losses from
injection in the maxilla or axilla or if myiasis resulted, and potential
marketing losses if animals or carcasses are discounted as a result of the
lesions. Risk factors for adverse reactions included inadequate restraint of
sheep, breed of sheep, experience of the operator, poor injection technique, and
inappropriate placement of vaccine. Increasing attention to the proper restraint
of animals, restricting vaccination to the recommended site behind the ear,
careful placement of the vaccine into subcutaneous tissue to avoid drainage of
vaccine material into tissues such as the spinal cord, and post-vaccination
supervision to address welfare concerns should adverse reactions occur are
recommended.
PMID- 17028664
TI - Male pseudohermaphroditism in a Labrador Retriever, and a review of mammalian
sexual differentiation.
AB - CASE HISTORY: An 8-month-old Labrador Retriever was referred with a history of
ambiguous external genitalia. CLINICAL FINDINGS AND TREATMENT: Clitoromegaly
within apparent vulval folds, and an adjacent subcutaneous mass were noticed on
external examination. An intra-abdominal testicle, with epididymis and suspected
vas deferens ducts, was found during exploratory celiotomy. Incision over the
subcutaneous mass revealed the accompanying testicle. Clitoridectomy was
performed and an os clitoris removed. Normal juvenile testes were diagnosed on
histology of the gonads. Chromosomal studies revealed a normal 78, XY male
chromosomal constitution. Due to the combination of a male karyotype (78, XY),
the presence of testicular tissue in the gonads, and the appearance of the
external genitalia, a diagnosis of male pseudohermaphroditism (MPH) was made.
CLINICAL RELEVANCE: This case presents the first report of MPH in a Labrador
Retriever, and highlights the diagnostic steps recommended when confronted with a
dog with ambiguous external genitalia.
PMID- 17028663
TI - Canine gastrinoma: a case study and literature review of therapeutic options.
AB - CASE HISTORY: A 6.2 kg, 8-year-old, spayed female Australian Terrier was
presented with weight loss, inappetence, lethargy and a 2-day history of
intermittent vomiting. CLINICAL FINDINGS: The dog had cranial abdominal pain and
there was melaena present on digital rectal examination. Haematology revealed a
marked, acute leucogram. DIAGNOSIS AND TREATMENT: Fasting serum gastrin levels
were markedly elevated and gastrinoma was suspected. Treatment was initiated with
omeprazole, ranitidine and sucralfate. The dog remained clinically normal for 26
months, at which time exploratory surgery was undertaken and the dog subsequently
euthanised due to extensive metastases. Histopathology and immunocytochemistry
confirmed the diagnosis of metastatic gastrinoma. CLINICAL RELEVANCE: This is a
rare condition infrequently reported. Although the number of cases treated with
omeprazole are too few to draw firm conclusions, it would appear that proton pump
inhibitors are useful and should be considered for cases of gastrinoma managed
medically. Long-term prognosis is poor, and survival times range from 1 to 147
weeks. Many treatment options are discussed in the medical literature though not
all are feasible in veterinary patients.
PMID- 17028665
TI - Confirmation of the occurrence of the chewing louse Bovicola (Lepikentron)
breviceps (Insecta: Phthiraptera: Trichodectidae) on alpacas (Lama pacos) in New
Zealand.
PMID- 17028666
TI - Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic
strategy for inflammatory disorders.
AB - Interleukin (IL)-6 contributes to a myriad of physiologic and pathophysiologic
processes. Among its many physiologic functions, IL-6 plays an active role in
immunology, inflammatory responses, bone metabolism, arthritis and neoplasia.
Overproduction of IL-6 has been implicated in the disease pathology of several
inflammatory and autoimmune disorders, including rheumatoid arthritis,
Castleman's disease, Crohn's disease and systemic-onset juvenile idiopathic
arthritis. Interception of the IL-6 signaling pathway could thus represent a new
treatment option for these diseases, given their refractory status to
conventional therapy. Clinical studies with tocilizumab, a humanized monoclonal
anti-IL-6 receptor antibody, have been undertaken to explore this option. Current
short-term results indicate that tocilizumab dramatically improves disease
activity and is well tolerated. Further long-term safety and efficacy studies are
needed to confirm the therapeutic benefit of this antibody in inflammatory and
autoimmune disorders.
PMID- 17028667
TI - Ruboxistaurin.
AB - Ruboxistaurin is a potent and specific inhibitor of the beta isoform of protein
kinase C. Overactivation of protein kinase C has been demonstrated in patients
with type 2 diabetes, and is postulated to play a major role in the pathogenesis
of diabetic microvascular complications, which include diabetic retinopathy,
neuropathy and nephropathy. The role of protein kinase C in promoting tissue
injury in patients with diabetes, and the pharmacologic and clinical studies
illustrating the potential of ruboxistaurin to reduce the burden of diabetic
microvascular complications will be discussed in this article.
PMID- 17028668
TI - Ropinirole treatment for restless legs syndrome.
AB - In this paper we discuss therapy with ropinirole (known as adartrel in the United
Kingdom) in patients with restless legs syndrome. Restless legs syndrome is
characterized by an urge to move the legs, uncomfortable sensations in the legs
and worsening of these symptoms during rest with at least temporary relief
brought on by activity. Current recommendations suggest dopaminergic therapy
(levodopa or dopamine receptor agonists like ropinirole) as the first-line
treatment for restless legs syndrome. Based on the results of randomized, placebo
controlled, double-blind trials, we conclude that ropinirole is effective in
reducing symptoms of restless legs syndrome in the general population. Ropinirole
has no serious or common side effects that would limit its use significantly.
Rebound and augmentation problems are relatively rarely seen with ropinirole,
although properly designed comparative trials are still needed to address this
question. It must be noted, however, that most published studies with ropinirole
compare this drug with placebo. Very few studies have compared ropinirole with
other drugs (L-dopa, gabapentin, opioids, benzodiazepines, other dopaminergic
agents and selegiline hydrochloride). No cost-effectiveness trial has been
published yet. Treatment of restless legs syndrome with ropinirole shows it to be
effective, well-tolerated and safe and it can be used in restless legs syndrome
in general.
PMID- 17028669
TI - Nanoparticle albumin-bound paclitaxel for treatment of metastatic breast cancer.
AB - Two taxanes, paclitaxel and docetaxel, are among the most widely used
chemotherapeutic agents in solid tumor oncology, with efficacy against tumors of
the breast, lung, head and neck, ovary, prostate, stomach and urothelium. The
taxanes have been studied extensively and have been proven effective for treating
early and advanced breast cancer. However, paclitaxel and docetaxel are both
highly hydrophobic compounds, requiring synthetic solvents for parenteral
administration. The solvents in commercially available preparations cause life
threatening toxic effects and decreased efficacy, and they are inconvenient to
administer. Nanoparticle albumin-bound paclitaxel (nabP) is a novel, solvent-free
formulation of paclitaxel. With nabP, in contrast to standard paclitaxel, life
threatening hypersensitivity reactions have not been observed, and it can be
administered safely without steroid and antihistamine premedication. Furthermore,
nabP exploits cellular and tumor transport mechanisms to preferentially target
tumor cells. Data from phase III studies of metastatic breast cancer demonstrated
higher response rates, longer time to progression and an improved toxicity
profile for nabP compared with standard paclitaxel. The U.S. Food and Drug
Administration approved nabP in late 2004 for treatment of metastatic breast
cancer after failure of an anthracycline-based regimen.
PMID- 17028670
TI - The roles of mucus-associated bacteria in inflammatory bowel disease.
AB - The etiology of inflammatory bowel disease (IBD) is currently unknown. Although
there is convincing evidence supporting a critical role for micro-organisms in
the pathogenesis of IBD, the specific organisms involved remain undetermined.
Mucus-associated bacteria have recently been considered as likely candidates for
involvement in IBD; indeed several mucus-associated bacteria species have been
shown to induce IBD-like conditions in animal models, and some of these bacteria
have been detected in human intestinal tissues. Further studies are required to
investigate the possible role of mucus-associated bacteria in human IBD.
PMID- 17028671
TI - Selective deoxygenation of sugar polyols to alpha,omega-diols and other oxygen
content reduced materials--a new challenge to homogeneous ionic hydrogenation and
hydrogenolysis catalysis.
AB - An oxygen atom on every carbon--this is the problem! While nature provides linear
C(3) to C(6) building blocks in the form of sugar alcohols in large and renewable
abundance, they are overfunctionalized for the purpose of most chemical
applications. Selective deoxygenation by anthropogenic catalyst systems may be
one answer to this challenge.
PMID- 17028672
TI - Structural and photophysical studies of phenanthrene adducts involving C6F5HgCl
and [o-C6F4Hg]3.
AB - Both pentafluorophenylmercury chloride and trimeric perfluoro-ortho-phenylene
mercury interact with phenanthrene to form phosphorescent adducts which exhibit
extended binary stacks in the solid state.
PMID- 17028673
TI - Mechanistic investigation of CO2 hydrogenation by Ru(II) and Ir(III) aqua
complexes under acidic conditions: two catalytic systems differing in the nature
of the rate determining step.
AB - Ruthenium aqua complexes [(eta(6)-C(6)Me(6))Ru(II)(L)(OH(2))](2+) {L = bpy (1)
and 4,4'-OMe-bpy (2), bpy = 2,2'-bipyridine, 4,4'-OMe-bpy = 4,4'-dimethoxy-2,2'
bipyridine} and iridium aqua complexes [Cp*Ir(III)(L)(OH(2))](2+) {Cp* = eta(5)
C(5)Me(5), L = bpy (5) and 4,4'-OMe-bpy (6)} act as catalysts for hydrogenation
of CO(2) into HCOOH at pH 3.0 in H(2)O. The active hydride catalysts cannot be
observed in the hydrogenation of CO(2) with the ruthenium complexes, whereas the
active hydride catalysts, [Cp*Ir(III)(L)(H)](+) {L = bpy (7) and 4,4'-OMe-bpy
(8)}, have successfully been isolated after the hydrogenation of CO(2) with the
iridium complexes. The key to the success of the isolation of the active hydride
catalysts is the change in the rate-determining step in the catalytic
hydrogenation of CO(2) from the formation of the active hydride catalysts,
[(eta(6)-C(6)Me(6))Ru(II)(L)(H)](+), to the reactions of [Cp*Ir(III)(L)(H)](+)
with CO(2), as indicated by the kinetic studies.
PMID- 17028674
TI - The first member of the eleven-vertex azadicarbaborane series, 1,6,9-NC2B8H13,
and its N-alkyl derivatives.
AB - Reactions between closo-1,2-C(2)B(8)H(10) (1) and amines of general formulation
R(1)R(2)NH (where R(1), R(2) = H, H; Me, H; t-Bu, H and Et, Et) resulted in a
straightforward cluster expansion and formation of the 11-vertex arachno
azadicarbaboranes of the 1,1-R(1),R(2-)1,6,9-NC(2)B(8)H(11) (2) cluster
constitution (where R(1), R(2) = H, H 2a; Me, H 2b; t-Bu, H 2c and Et, Et 2d) in
yields 10-75%, depending on the nature of the amine used. The reactions are the
first example of a direct closo to arachno transformation in the area of cluster
boron compounds. Compounds 2b and 2c were isolated in two isomeric forms anti-
and syn- that differ in the positioning of the t-Bu substituent with respect to
the bridging hydrogen site. Deprotonation of compounds 2 generally leads to
removal of the bridging proton and formation of the [1,1-R(1),R(2-)1,6,9
NC(2)B(8)H(11)](-) (2-) anions that, in the case of the monoalkylated Me and t-Bu
derivatives, adopt only an anti configuration. The structure of anti-2c was
determined by X-ray diffraction analysis and the geometries of the parent
compound and the corresponding syn and anti isomers were optimised at the RMP2/6
31G* level. The composition of all compounds is consistent with the results of
mass spectrometry and multinuclear ((1)H and (11)B) spectroscopy complemented by
two-dimensional [(11)B-(11)B]-COSY and (1)H{(11)B(selective)} NMR measurements.
Experimental (11)B chemical shifts generally show acceptable agreement with
theoretical values calculated by GIAO methods, in particular at GIAO-MP2/II,
where possible.
PMID- 17028675
TI - Pyridinyloxazolidines: versatile scaffolds for chiral catalyst construction.
AB - Pyridinyloxazolidines are structurally versatile chiral ligand frameworks that
are easily made and coordinated to Pd(II); the resulting complexes, which show
significant steric and electronic differences from their oxazoline counterparts,
as well as intermolecular H-bonding in the solid state, can be isolated in
diastereomerically pure form and are remarkably resistant to hydrolysis.
PMID- 17028676
TI - Synthesis, structure and fluorescent studies of novel uranium coordination
polymers in the pyridinedicarboxylic acid system.
AB - Self-assembly under hydrothermal conditions has been employed to synthesize
several novel uranium-containing polymeric materials in the pyridinedicarboxylic
acid (pydc) system. Uranium containing coordination polymers were synthesized
utilizing 2,3-pyridinedicarboxylic acid (2,3-pydc), 2,4-pyridinedicarboxylic acid
(2,4-pydc) and 2,6-pyridinedicarboxylic acid (2,6-pydc) as the organic linker.
Furthermore, several bimetallic compounds were also synthesized, U-M-2,6-pydc (M
= Cu, Ag, Pb). A new secondary building unit for uranium(vi) compounds has also
been realized in compound 4 [(UO(2))(2)(C(7)H(3)NO(4))(O)(H(2)O)] through
tetramer building units edge shared to form one-dimensional chains. Presented
herein will be the syntheses, crystal structures and fluorescent properties of
these uranium-containing compounds.
PMID- 17028677
TI - Kinetics and mechanism of the reaction of [RuIII(edta)(H2O)]- with HOBr to form
an intermediate RuV=O complex in aqueous solution.
AB - The interaction of [Ru(III)(edta)(H(2)O)](-) (1) (edta =
ethylenediaminetetraacetate) with the oxygen transfer agent HOBr, was studied
kinetically as a function of [HOBr] and temperature (5-35 degrees C) at a fixed
pH of 6.2. Spectroscopic evidence is reported for the formation of a high valent
intermediate (edta)Ru(V)=O complex. Water soluble 2,2'-azobis(3
ethylbenzithiazoline-6-sulfonate) (ABTS) was employed as a trap for this
intermediate in order to gain further mechanistic information. Reactions were
carried out under pseudo-first conditions for [ABTS] >> [HOBr] >> [1], and were
monitored as a function of time for the formation of the one-electron oxidation
product ABTS(*+). The reported kinetic data are interpreted in terms of a
suggested reaction mechanism and discussed in reference to data reported before.
PMID- 17028678
TI - Ferrocene-modified pyrimidine nucleosides: synthesis, structure and
electrochemistry.
AB - This paper reports syntheses, crystal structures and electrochemical results for
two ferrocene(Fc)-modified pyrimidine nucleosides that could potentially be used
for investigating electron transfer in DNA. Fc was directly attached to the 5
position of deoxyuridine and deoxycytidine via the Stille coupling reaction. Fc
modified uridine was incorporated into DNA trinucleotides with standard solid
phase synthesis. The structures of corresponding detritylated compounds were
determined by single-crystal X-ray analysis. Electrochemical investigations of
all compounds by cyclic voltammetry revealed reversible redox processes.
PMID- 17028679
TI - From structural properties of the EuIII complex with
ethylenediaminetetra(methylenephosphonic acid) (H8EDTMP) towards biomedical
applications.
AB - Crystals of Eu(III) with ethylenediaminetetra(methylenephosphonic acid)
(H(8)EDTMP) and with ethylenediaminetetraacetic acid (H(4)EDTA) have been
synthesized in the same experimental conditions and their X-ray analyses have
been performed. The EDTMP ligand wraps the Eu(III) ion in a fashion similar to
its carboxylic analogue, EDTA, i.e. coordinating through two nitrogen atoms and
four oxygen atoms in such a way that only one oxygen atom from each phosphonate
group is bonded to the central ion. The coordination sphere is completed by two
oxygen atoms of the bidentate carbonate anion in the case of the Eu(III)-EDTMP
complex, whereas the inner sphere of the Eu(III)-EDTA crystal is completed by
three water molecules. Spectroscopic studies (UV-Vis and (31)P NMR spectra) of
Eu(III)-EDTMP solutions at controlled pH showed that the replacement of inner
sphere water molecules and/or OH hydroxy groups by a carbonate anion in the
Eu(III)-EDTMP complex at physiological pH results in the formation of
[Eu(EDTMP)(CO(3))](7-) species which is thermodynamically stable and kinetically
inert. The affinity of the carbonate anion towards the Eu(III)-EDTMP species was
studied by analysis of f-f intensities and luminescence decay rates. The
dissociation constant of the Eu(III)-EDTMP-carbonate complex was found to be
approximately 43 mM. The presented results may be helpful in understanding the
role played by the (153)Sm(III)-EDTMP complex known as Quadramet in the seeking
of metastatic tissue in bones as well as possibly giving some premises for future
ligand design of these types of complexes with lanthanide radionuclides.
PMID- 17028680
TI - Complexation behaviour and stability of Schiff bases in aqueous solution. The
case of an acyclic diimino(amino) diphenol and its reduced triamine derivative.
AB - The copper(II), nickel(II), and zinc(II) complexes of the acyclic Schiff base
H(2)L(A), obtained by [1 + 2] condensation of 1,2-ethanediamine,N-(2-aminoethyl)
N-methyl with 3-ethoxy-2-hydroxybenzaldehyde, and of H(2)L(B), the reduced
derivative of H(2)L(A), were prepared and their properties studied by IR, NMR and
SEM-EDS. In these complexes, the metal ion is always located in the coordination
chamber of the ligand delimited by two phenol oxygens and nitrogen atoms (either
aminic or iminic). The coordination behaviour of H(2)L(A) and H(2)L(B) towards
H(+), Cu(2+), Ni(2+) and Zn(2+) in aqueous solution at 298 K and mu = 0.1 mol dm(
3) (Na)ClO(4) was also studied by potentiometric, NMR and UV-VIS measurements. In
particular, potentiometric equilibrium studies indicate that H(2)L(A) is not
stable enough to have a pH range in which it is the sole species in aqueous
solution. In such a solution, the Schiff base forms over a limited pH range,
between 6 and 10, with a maximum formation percentage at pH approximately 9. In
addition, the involvement of imine nitrogens in the complexes markedly stabilises
the azomethylene linkage, so that the metal complexes of H(2)L(A), particularly
those of copper(II), are the species largely prevailing in solutions with pH
>3.5. The stability constants of the complexes formed by metal ions with H(2)L(A)
and H(2)L(B) follow the order Cu(2+) >> Ni(2+) > Zn(2+); distribution plots show
that copper(II) gives complexes more stable with H(2)L(A), whereas Ni(2+) and
Zn(2+) prefer the reduced ligand, H(2)L(B).
PMID- 17028681
TI - Formation of a solubilized cobalt block oligomer from a M2L-type double helicate.
AB - The multi-dentate ligand, 2,3,5,6-tetrakis(2,2'-bipyridyl)pyrazine (L) and
divalent cobalt self-assemble to a block co-polymer-like oligomer in solution,
which contains at least the L(7)Co(8) fragment. The extent of oligomerization is
sensitive to the water content in acetonitrile solution. In the solid state, the
simple monomer [LCo(2)(CH(3)CN)(4)][ClO(4)](4) is isolated. The X-ray structure
of the crystallized material (containing four CH(3)CN solvate molecules) reveals
a double-helical complex with two heptadentate Co(II) sites, and a helical pitch
of approximately 28.1 A. Coupled Co(I/II) redox processes are observed between
the two metal centres.
PMID- 17028682
TI - Tricyclohexylphosphine-cyclopalladated ferrocenylimine complexes: synthesis,
crystal structures and application in Suzuki and Heck reactions.
AB - A series of novel tricyclohexylphosphine (PCy(3))-cyclopalladated ferrocenylimine
complexes 2c-2g have been easily synthesized. These new palladacycles are
thermally stable and are not sensitive to air and moisture. Their detailed
structures have been determined by single-crystal X-ray analysis and six
different types of intermolecular hydrogen bonds are found to be existed in the
crystals of these complexes. The use of 2c-2g as catalysts for Suzuki and Heck
reactions was examined. They were found to be very efficient for the Suzuki
reaction of aryl chlorides with phenylboronic acid. Typically, using 0.1 mol% of
catalyst in the presence of 1.5 equivalent of Cs(2)CO(3) as base in dioxane at
100 degrees C provided coupled products in excellent yields. These complexes also
displayed good activity in the Heck reaction of a range of aryl bromides with
acrylic acid ethyl ester although they were not particularly useful for the
activation of aryl chlorides.
PMID- 17028683
TI - Functional polymers: scanning force microscopy insights.
AB - Scanning force microscopy (SFM) and related techniques make it possible to
visualize polymer systems with a molecular resolution. Beyond imaging, they also
enable the unveiling of a variety of (dynamic) physico-chemical properties of
both isolated polymer chains and their supramolecular architectures, including
structural, mechanical and electronic properties. This article reviews recent
progress in the use of SFM on polymers, with a particular emphasis on the
mechanical properties of copolymers and single polymer chains, as well as on the
bottom-up fabrication of supramolecular polymeric (helical) nanostructures in
particular based upon pi-conjugated macromolecules as building blocks for
nanoelectronics. Through a detailed understanding of the polymer behavior, we
propose solutions for the generation of organic functional (nano)systems.
PMID- 17028684
TI - On determining the nuclearity of iron sites in Fe-ZSM-5--a critical evaluation.
AB - In order to interpret catalytic data on iron zeolites in terms of structure
activity relationships, reliable characterisation methods are needed. In
particular, the nuclearity of the iron species is an important issue, since it is
often invoked to explain catalytic activity. In the present contribution, we
address the problem of the nuclearity of the iron species in Fe-ZSM-5 by a
combination of techniques, that is, UV-Vis, EXAFS, Magnetic Circular Dichroism
(MCD) and magnetisation measurements. Based on an in-depth analysis of these
data, we show that some of the current interpretations of UV-Vis and EXAFS
spectra need to be revised.
PMID- 17028685
TI - Parity conservation and polarization of differential cross sections in complex
forming chemical reactions.
AB - For complex-forming chemical reactions, such as atom-diatom insertion reactions,
quantum scattering and quantum statistical calculations usually predict sharp
forward/backward peaks in the Differential Cross Sections (DCS). Conversely, the
corresponding classical calculations are unable to reproduce these peaks. We show
here that the basic reason for such an intriguing failure is that parity
conservation is ignored in classical mechanics. A by-product of the analysis is a
simple parity-restoring approximation that might significantly increase the
ability of classical mechanics to describe DCSs over the whole angular range for
the title processes.
PMID- 17028686
TI - Treating dispersion effects in extended systems by hybrid MP2:DFT calculations-
protonation of isobutene in zeolite ferrierite.
AB - We propose use of a hybrid method to study problems that involve both bond
rearrangements and van-der-Waals interactions. The method combines second-order
Moller-Plesset perturbation theory (MP2) calculations for the reaction site with
density functional theory (DFT) calculations for a large system under periodic
boundary conditions. Hybrid MP2:DFT structure optimisation for a cluster embedded
in the periodic model is the first of three steps in a multi-level approach. The
second step is extrapolation of the MP2 energy to the complete basis set limit.
The third step is extrapolating the high-level (MP2) correction to the limiting
case of the full periodic structure. This is done by calculating the MP2
correction for a series of cluster models of increasing size, fitting an analytic
expression to these energy corrections, and applying the fitted expression to the
full periodic structure. We assume that, up to a constant, the high-level
correction is described by a damped dispersion expression. Combining the results
of all three steps yields an estimate of the MP2 reaction energy for the full
periodic system at the complete basis set level. The method is designed for a
reaction between a small or medium sized substrate molecule and a very large
chemical system. For adsorption of isobutene in zeolite H-ferrierite, the
energies obtained for the formation of different structures, the pi-complex, the
isobutoxide, the tert-butoxide, and the tert-butyl carbenium ion, are -78, -73,
48, and -21 kJ mol(-1), respectively. This corresponds to corrections of the pure
DFT (PBE functional) results by -62, -70, -67, and -29 kJ mol(-1), respectively.
Hence, the MP2 corrections are substantial and, perhaps more importantly, not the
same for the different hydrocarbon species in the zeolite. Coupled-cluster
(CCSD(T)) calculations change the MP2 energies by -4 kJ mol(-1) (tert-butyl
cation) or less (below +/-1 kJ mol(-1) for the other species).
PMID- 17028687
TI - On the origin of the redshift of the OH stretch in Ice Ih: evidence from the
momentum distribution of the protons and the infrared spectral density.
AB - Recent measurements of the momentum distribution in water and ice have shown that
the proton is in a considerably softer potential in ice Ih than in water or the
free monomer. This is broadly consistent with the large red shift observed in the
vibrational spectrum. We show that existing water models, which treat the
intramolecular potential as unchanged by the hydrogen bonding are unable to
reproduce the momentum distribution. In addition, even if they can substantially
explain the red shift they are unable to explain the large increase in intensity
observed in the infrared spectrum in going from the monomer to ice Ih. We show
that the inclusion of a bond dipole derivative term is essential to explain the
observed intensities in the infrared spectrum. Though this term is partially
responsible for the softening of the effective potential of the proton we show
that best agreement with the observed momentum distribution requires a further
softening of the harmonic component of the intramolecular potential. We introduce
an efficient normal-mode molecular dynamics algorithm for calculating the
momentum distribution with path-integrals.
PMID- 17028688
TI - Time-resolved photoelectron and photoion fragmentation spectroscopy study of 9
methyladenine and its hydrates: a contribution to the understanding of the
ultrafast radiationless decay of excited DNA bases.
AB - The excited state dynamics of the purine base 9-methyladenine (9Me-Ade) has been
investigated by time- and energy-resolved photoelectron imaging spectroscopy and
mass-selected ion spectroscopy, in both vacuum and water-cluster environments.
The specific probe processes used, namely a careful monitoring of time-resolved
photoelectron energy distributions and of photoion fragmentation, together with
the excellent temporal resolution achieved, enable us to derive additional
information on the nature of the excited states (pipi*, npi*, pisigma*, triplet)
involved in the electronic relaxation of adenine. The two-step pathway we propose
to account for the double exponential decay observed agrees well with recent
theoretical calculations. The near-UV photophysics of 9Me-Ade is dominated by the
direct excitation of the pipi* ((1)L(b)) state (lifetime of 100 fs), followed by
internal conversion to the npi* state (lifetime in the ps range) via conical
intersection. No evidence for the involvement of a pisigma* or a triplet state
was found. 9Me-Ade-(H(2)O)(n) clusters have been studied, focusing on the
fragmentation of these species after the probe process. A careful analysis of the
fragments allowed us to provide evidence for a double exponential decay profile
for the hydrates. The very weak second component observed, however, led us to
conclude that the photophysics were very different compared with the isolated
base, assigned to a competition between (i) a direct one-step decay of the
initially excited state (pipi* L(a) and/or L(b), stabilised by hydration) to the
ground state and (ii) a modified two-step decay scheme, qualitatively comparable
to that occurring in the isolated molecule.
PMID- 17028689
TI - The heterogeneous kinetics of HOBr and HOCl on acidified sea salt and model
aerosol at 40-90% relative humidity and ambient temperature.
AB - The HOBr and HOCl uptake coefficient gamma on H(2)SO(4)-acidified submicron salt
aerosol of known size distribution was measured in an atmospheric pressure
laminar flow reactor. The interaction time of the trace gas with the aerosol was
in the range 15 to 90 s and led to gamma values in the range 10(-4) to 10(-2).
The acidity of the aerosol is essential in order to enable heterogeneous
reactions of HOBr on NaCl, recrystallized sea salt (RSS) and natural sea salt
(NSS) aerosols. Specifically, HOCl only reacts on acidified NSS aerosol with a
gamma ranging from 0.4 x 10(-3) to 1.8 x 10(-3) at a relative humidity (rh) at 40
and 85%, respectively. Uptake experiments of HOBr on aqueous H(2)SO(4) as well as
on H(2)SO(4)-acidified NaCl, RSS or NSS aerosol were performed for rh ranging
from 40 to 93%. The gamma value of HOBr on acidified NSS reaches a maximum gamma
= 1.9 x 10(-2) at rh = 76 +/- 1% and significantly decreases with increasing rh
in contrast to acidified NaCl and RSS aerosols whose gamma values remain high at
gamma = (1.0 +/- 0.2) x 10(-2) at rh >/= 80%. An explanation based on the
formation of an organic coating on NSS aerosol with increasing rh is proposed.
PMID- 17028691
TI - Is perturbation DFT approach applicable to purely repulsive fluids?
AB - A recently proposed third order + second order perturbation density functional
theory (DFT) approach is tested for the validity and applicability to purely
repulsive model fluids subjected to various external fields. Hard core repulsive
Yukawa potential, point particle Yukawa potential, and inverse power potential
are employed as sample models. Theoretical DFT results are compared with the
corresponding simulation data obtained by grand canonical ensemble Monte Carlo
simulation. This comparison indicates that the third order + second order
perturbation DFT approach is suitable for these purely repulsive fluids only on
condition of high accuracy of the imported bulk second order direct correlation
function (DCF). However, in this case the origin of the successful performance
somewhat differs from that observed for the mean field approximation applied to
van der Waals fluids. In the present case it originates from the observation that
the bulk second order DCF is strongly dependent on the density argument for the
hard-core part, while for the distances exceeding the core dimension this
dependence is considerably weaker.
PMID- 17028690
TI - Detection of hydrogen bonding in solution: a 2H nuclear magnetic resonance method
based on rotational motion of a donor/acceptor complex.
AB - The effect of hydrogen bonding on the rotational correlation time of an H-bond
acceptor, pyridine N-oxide-d(5), in various solvents was investigated using the
(2)H spin-lattice relaxation time (T(1)). The results demonstrate a linear
relationship between viscosity and measured rotational correlation times, an
example of Stokes-Einstein-Debye behavior. The results also clearly demonstrate
reduced rotational rates for the probe in hydrogen bonding solvents in comparison
to solvents incapable of forming hydrogen bonds with the probe. The utility of
this observation was exploited to estimate the association constant (K(a))
through an NMR titration procedure. These results are presented as a new
technique that can be applied to the characterization of hydrogen bonding in
similar systems.
PMID- 17028692
TI - On the nature of metallic nanoparticles obtained from molecular Co3Ru-carbonyl
clusters in mesoporous silica matrices.
AB - We report on the impregnation of THF solutions of the low-valent heterometallic
cluster NEt(4)[Co(3)Ru(CO)(12)] into two mesoporous silica matrices, amorphous
xerogels and ordered MCM-41, and a study of its thermal decomposition into
metallic nanoparticles by X-ray diffraction, transmission electron microscopy and
in situ magnetic measurements under controlled atmospheres. The decomposition of
the cluster was monitored as a function of temperature by examining the chemical
composition of the particles, their size distributions and their structures as
well as their magnetic properties. Treatment under inert atmosphere (i.e. argon)
at temperatures below 200 degrees C resulted in the formation of segregated
spherical particles of hcp-ruthenium (2.3 +/- 1.0 nm) and hcp-cobalt (3.1 +/- 0.9
nm). The latter is transformed to fcc-cobalt (3.2 +/- 1.0 nm) above 270 degrees
C. At higher temperatures, Co-Ru alloying takes place and the Ru content of the
particles increases with increasing temperature to reach the nominal composition
of the molecular precursor, Co(3)Ru. The particles are more evenly distributed in
the MCM-41 framework compared to the disordered xerogel and also show a narrower
size distribution. Owing to the different magnetic anisotropy of hcp- and fcc
cobalt, which results in different blocking temperatures, we were able to clearly
identify the products formed at the early stages of the thermal decomposition
procedure.
PMID- 17028693
TI - Quantitative measurement and interpretation of optical second harmonic generation
from molecular interfaces.
AB - Second harmonic generation (SHG) has been proven a uniquely effective technique
in the investigation of molecular structure and conformations, as well as
dynamics of molecular interfaces. The ability to apply SHG to molecular interface
studies depends on the ability to abstract quantitative information from the
measurable quantities in the actual SHG experiments. In this review, we try to
assess recent developments in the SHG experimental methodologies towards
quantitative analysis of the nonlinear optical properties of the achiral
molecular interfaces with rotational isotropy along the interface normal. These
developments include the methodology for orientational analysis of the SHG
experimental data, the experimental approaches for more accurate SHG
measurements, and a novel treatment of the symmetry properties of the molecular
polarizability tensors in association with the experimentally measurable
quantities. In the end, the recent developments on the problem of surface versus
bulk contribution in SHG surface studies is discussed. These developments can put
SHG on a more solid foundation for molecular interface studies, and to pave the
way for better understanding and application of SHG surface studies in general.
PMID- 17028695
TI - Calculation of intermolecular interactions in the benzene dimer using coupled
cluster and local electron correlation methods.
AB - Potential energy curves for the parallel-displaced, T-shaped and sandwich
structures of the benzene dimer are computed with density fitted local second
order Moller-Plesset perturbation theory (DF-LMP2) as well as with the spin
component scaled (SCS) variant of DF-LMP2. While DF-LMP2 strongly overestimates
the dispersion interaction, in common with canonical MP2, the DF-SCS-LMP2
interaction energies are in excellent agreement with the best available
literature values along the entire potential energy curves. The DF-SCS-LMP2
dissociation energies for the three structures are also compared with new
complete basis set estimates of the interaction energies obtained from accurate
coupled cluster (CCSD(T)) and DF-SCS-MP2 calculations. Since LMP2 is essentially
free of basis set superposition errors, counterpoise corrections are not
required. As a result, DF-SCS-LMP2 is computationally inexpensive and represents
an attractive method for the study of larger pi-stacked systems such as truncated
sections of DNA.
PMID- 17028694
TI - Protein-bound chromophores astaxanthin and phytochromobilin: excited state
quantum chemical studies.
AB - We present an overview of excited state quantum chemical calculations aimed at
elucidating controversial issues regarding the photochemistry of the protein
bound chromophores astaxanthin and phytochromobilin. In particular, we show how
the application of time-dependent density functional theory and other single
reference quantum chemical excited state methods have contributed to shed new
light on the origin of the >0.5 eV bathochromic shift of the electronic
absorption by the carotenoid astaxanthin in the protein macromolecular complex
crustacyanin, and the mechanism for C15-Z,syn --> C15-E,anti isomerization of the
tetrapyrrole phytochromobilin that underlies the photoactivation of the plant
photoreceptor phytochrome. Within the approximation that exciton coupling is
neglected, the calculations on astaxanthin provide support for the notion that
the bathochromic shift, which is responsible for the slate-blue coloration of
lobster shell, is due to polarization rather than a conformational change of the
chromophore in the protein-bound state. Furthermore, the polarization is
attributed to a hydrogen-bonded protonated histidine residue. The calculations on
phytochromobilin, in turn, suggest that a stepwise C15-Z,syn --> C15-E,syn
(photochemical), C15-E,syn --> C15-E,anti (thermal) mechanism is much more
favorable than a concerted, fully photochemical mechanism, and that neutral forms
of the chromophore are much less likely to photoisomerize than the parent,
protonated form. Accordingly, the calculations indirectly support the view that
the photoactivation of phytochrome does not involve a proton transfer from the
chromophore to the surrounding protein.
PMID- 17028696
TI - Scalar relativistic calculations of hyperfine coupling tensors using the Douglas
Kroll-Hess method with a finite-size nucleus model.
AB - A scalar relativistic method to calculate hyperfine coupling tensors at the
Douglas-Kroll-Hess level has been extended to incorporate a finite-size nucleus
model using a Gaussian charge and magnetic moment distribution. Density
functional calculations at gradient-corrected and hybrid functional levels have
been carried out for the group 11 atoms and for a set of small group 12
molecules, comparing nonrelativistic as well as scalar relativistic results at
second-order Douglas-Kroll-Hess level with and without finite-size nucleus. While
nonrelativistic calculations underestimate isotropic hyperfine couplings
increasingly with increasing nuclear charge, scalar relativistic calculations
with point nucleus provide somewhat overestimated values. Inclusion of the finite
size nuclear model in the calculation of the wavefunction, and in the transformed
hyperfine operators both decrease the magnitude of the hyperfine couplings. The
effects, which are cumulative, improve agreement with experiment.
PMID- 17028697
TI - How are the ready and unready states of nickel-iron hydrogenase activated by H2?
A density functional theory study.
AB - We have explored possible mechanisms for the formation of the catalytically
active Ni(a)-S state of the enzyme, nickel iron hydrogenase, from the Ni*(r)
(ready) or Ni*(u) (unready) state, by reaction with H(2), using density
functional theory calculations with the BP86 functional in conjunction with a
DZVP basis set. We find that for the reaction of the ready state, which is taken
to have an -OH bridge, the rate determining step is the cleavage of H(2) at the
Ni(3+) centre with a barrier of approximately 15 kcal mol(-1). We take the
unready state to have a -OOH bridge, and find that reaction with H(2) to form the
Ni(r)-S state can proceed by two possible routes. One such path has a number of
steps involving electron transfer, which is consistent with experiment, as is the
calculated barrier of approximately 19 kcal mol(-1). The alternative pathway,
with a lower barrier, may not be rate determining. Overall, our predictions give
barriers in line with experiment, and allow details of the mechanism to be
explored which are inaccessible from experiment.
PMID- 17028698
TI - Spatial distribution of stabilizer-derived nitroxide radicals during thermal
degradation of poly(acrylonitrile-butadiene-styrene) copolymers: a unified
picture from pulsed ELDOR and ESR imaging.
AB - Double Electron-Electron Resonance (DEER) provides information on the spatial
distribution of radicals on the length scale of a few nanometres, while Electron
Spin Resonance Imaging (ESRI) provides information on a length scale of
millimetres with a resolution of about 100 micrometres. Despite the gap between
these length scales, results from the two techniques are found to complement and
support each other in the characterization of the identity and distribution of
nitroxide radicals derived from the Hindered Amine Stabilizer (HAS) Tinuvin 770
in poly(acrylonitrile-butadiene-styrene) (ABS) copolymers. DEER measurements
demonstrate that there is no significant formation of biradicals from the
bifunctional HAS, and provide the distributions of local radical concentrations.
These distributions are poorly resolved for model-free analysis of the DEER data
by the Tikhonov regularization; the resolution was significantly improved by
utilizing information obtained by ESRI. DEER data can be fitted with only one
adjustable parameter, namely the average radical concentration, if 1D and 2D
spectral--spatial ESRI results on both the spatial distribution of nitroxides and
their distribution between the acrylonitrile--styrene-rich (SAN) and butadiene
rich (B) microphases are considered.
PMID- 17028699
TI - Synthesis and photophysical properties of a [60]fullerene compound with
dimethylaniline and ferrocene connected through a pyrazolino group: a study by
laser flash photolysis.
AB - Pyrazolino[60]fullerene covalently-linked to ferrocene and N,N-dimethylaniline
groups has been prepared and studied using time-resolved spectroscopic methods.
The fluorescence quenching of the C(60) moiety indicates that charge-separation
takes place via the singlet excited state of the C(60) moiety in both polar and
non-polar solvents. The charge-separated state, in which an electron is localized
on the C(60) sphere and a hole is located on the whole donor moieties of
ferrocene, pyrazole, and N,N-dimethylaniline groups, has been confirmed by
nanosecond transient spectra in the visible and near-IR spectral region. The
lifetimes of the radical ion-pairs are as long as 30 - 50 ns in both polar and
non-polar solvents.
PMID- 17028700
TI - Competing through-space and through-bond, intramolecular triplet-energy transfer
in a supposedly rigid ruthenium(II) tris(2,2'-bipyridine)--fullerene molecular
dyad.
AB - A ditopic ruthenium(II) tris(2,2'-bipyridyl)-based fullerene conjugate has been
synthesized so as to separate the photoactive terminals by way of a short
ethynylene spacer group that is expected to act as a rigid rod. Intramolecular
triplet-energy transfer from the metal complex to the fullerene is quantitative
at all temperatures and there is no indication for competing electron transfer.
Temperature dependence studies indicate two pathways for triplet-energy transfer.
An activationless route dominates at low temperature and is attributed to through
bond electron exchange that takes place via super-exchange interactions. The
triplet energy of the bridging unit lies well above that of the metal complex. An
activated process is switched-on at high temperatures and is believed to involve
through-space electron exchange within closed conformations. Molecular dynamics
simulations predict that, in addition to an extended conformation, the linker can
distort in such a way that the terminals come into orbital contact. In fact, the
resultant closed conformation possesses an idealised geometry for fast electron
exchange.
PMID- 17028701
TI - Two grid refinement methods in the lattice Boltzmann framework for reaction
diffusion processes in complex systems.
AB - This paper studies the optimisation of a numerical model and a computer code to
solve numerically reaction-diffusion processes in environmental or biological
systems with complicated geometries and mixtures of reactions including time and
spatial scales extending over several order of magnitude. In particular, we
consider different grid refinement techniques in the framework of a lattice
Boltzmann solver for reaction-diffusion systems. Two new grid refinement methods
are proposed, which are both quantitatively good. The first method is based on
the matching of the concentration profiles and fluxes across two adjacent sub
domains, while the second method is based on nested subgrids. The focus of our
study is the trade off between accuracy and CPU time. We show how the different
parameters of the method, such as the refinement factors, the location of the
boundary between different grids or coupling methods at the interface affect the
quality of the numerical solution and the efficiency of the method.
PMID- 17028702
TI - Scanning pyroelectric microscopy revealing the spatial polarity distribution in
topologically centric crystals of trans-4-chloro-4'-nitrostilbene.
AB - Scanning pyroelectric microscopy (SPEM) was applied to investigate grown-in
polarity in trans-4-chloro-4'-nitrostilbene (CNS) single crystals. Sectors {011}
and {011} were scanned for cross sections perpendicular to the a-direction. A
rotational analysis for {011}, {011} faces was performed for a needle like
crystal turned around the a-axis. All pyroelectric experiments confirm a bipolar
grown-in state of polarity for sector involving the twofold axis b. These
measurements agree with theoretical force field and stochastic calculations,
predicting a bipolar state and a nearly identical extent of polarity for two
different sectors.
PMID- 17028704
TI - Triruthenium and triosmium carbonyl clusters containing chiral bidentate NHC
thiolate ligands derived from levamisole.
AB - The trinuclear complexes [M3(mu-Cl)(mu-S approximately CH)(CO)9] (M=Ru, Os; S
approximately CH=1-ethylenethiolate-3-H-4-(S)-phenylimidazolin-2-ylidene) and
[M3(mu-H)(mu-S approximately CMe)(CO)9] (M=Ru, Os; S approximately CMe=1
ethylenethiolate-3-methyl-4-(S)-phenylimidazolin-2-ylidene) have been prepared by
treating [Ru3(CO)12] and [Os3(CO)10(MeCN)2] with levamisolium chloride or [M3(mu
H)(CO)11]- with methyl levamisolium triflate, respectively. The chiral N
heterocyclic carbene-thiolate ligands S approximately CH and S approximately CMe
arise from the oxidative addition of the C-S bond of levamisolium or methyl
levamisolium cations to anionic trinuclear clusters.
PMID- 17028703
TI - The role of electrochemistry in the development of pi-basic dearomatization
agents.
AB - Dihapto-coordination of aromatic molecules promotes numerous organic
transformations that are not observed for the free aromatics. The development of
osmium, rhenium, tungsten and molybdenum complexes that are capable of such
binding is described in this perspective. The stability of these complexes
strongly correlates to the metal d5/d6 reduction potential and electrochemical
data has played a central role in their design.
PMID- 17028705
TI - Crystal structure of lead(II) acetylacetonate and the structure of the
acetylacetone solvated lead(II) ion in solution studied by large-angle X-ray
scattering.
AB - The crystal structure of bis(acetylacetonato)lead(II) and the structure of the
acetylacetone solvated lead(II) ion in solution have been determined by single
crystal X-ray diffraction and large-angle X-ray scattering (LAXS), respectively.
The acetylacetone is deprotonated and acts as a bidentate anionic ligand (acac-)
in the solid Pb(acac)2 compound. The lead(II) ion binds four oxygen atoms
strongly in a nearly flat pyramidal configuration with Pb-O bond lengths in the
range 2.32-2.37 A, and additionally three oxygens from neighboring complexes at
3.01-3.26 A. Acetylacetone acts as a solvent (Hacac) at dissolution of lead(II)
trifluoromethanesulfonate forming a pentasolvate with a mean Pb-O bond distance
of 2.724(5) A. The 6s2 lone electron pair on the lead(II) ion becomes
stereochemically active in the crystalline acetylacetonate complex, while it is
inactive in the solvate in solution. The solution was also analysed using IR and
1H NMR spectroscopy.
PMID- 17028706
TI - New discrete and polymeric supramolecular architectures derived from dinuclear
(bis-beta-diketonato)copper(II) metallocycles.
AB - New examples of adducts between di- (and, in one instance, tetra-) functional
nitrogen ligands and planar 'platform-like' dinuclear copper(II) complexes,
[Cu2L2], incorporating the 1,3-aryl linked bis-beta-diketonato bridging ligand
1,1'-(1,3-phenylene)-bis(4,4-dimethylpentane-1,3-dione) (H2L) have been
synthesised. The X-ray structures of six adduct species are reported. The
interaction of [Cu2(L)2] with the ditopic ligand aminopyrazine (apyz) yielded the
sandwich-like tetranuclear species [(Cu2L2(apyz))2]. A variable-temperature
magnetochemical investigation of this product indicated weak antiferromagnetic
coupling between the (five-coordinate) copper centres, mediated by the 2
aminopyrazine linkers. An analogous structure, [(Cu2L2(dabco))2] (dabco=1,4
diazabicyclo[2.2.2]octane), was generated when dabco was substituted for
aminopyrazine while use of 4,4'-dipyridyl sulfide (dps) and 4,4'-(1,3-xylylene)
bis(3,5-dimethylpyrazole) (xbp) as the ditopic 'spacer' ligands resulted in
polymeric species of type [Cu2L2(dps)]n and [Cu2L2(xbp)]n, respectively. These
latter species exist as one-dimensional chain structures in which copper(II)
centres on different dinuclear platforms are linked in a 'zigzag' fashion. In
contrast, with 2,2'-dipyridylamine (dpa) a discrete complex of type [Cu2L2(dpa)2]
formed in which one potential pyridyl donor from each 2,2'-dipyridylamine ligand
remains uncoordinated. The use of the potentially quadruply-bridging
hexamethylenetetramine (hmt) ligand as the linker unit was found to give rise to
an unusual two-dimensional polymeric motif of type [(Cu2(L2)2)3(hmt)2]n. The
product takes the form of a (6,3) network, incorporating triply bridging
hexamethylenetetramine units.
PMID- 17028707
TI - Assembled monolayers of Mo3S4(4+) clusters on well-defined surfaces.
AB - A class of inorganic monolayers formed by assembling the molybdenum-sulfur
cluster, Mo3S4(4+), onto a well-defined Au(111) surface is presented. The
monolayers have been comprehensively characterized by electrochemistry, X-ray
photoelectron spectroscopy (XPS), and in situ scanning tunneling microscopy (in
situ STM). The voltammetric data show strong reductive and oxidative desorption
signals from Au-S interactions, supported by the presence of both S and Mo
signals in XPS. In situ STM shows many small pits in the dense adlayers uniformly
spread over the surface, which is a typical feature of self-assembled monolayers
(SAMs) of alkanethiols. The density of the pits is ca. 23 (+/-5)% and is
significantly higher than for straight-chain alkanethiol SAMs with a single -SH
group. The pit shapes are irregular, suggesting multiple Au-S interactions from
Mo3S4(4+). High resolution images disclose bright round spots of ca. 8 A diameter
representing individual molecules in the SAM. This is the first example of in
situ monolayer formation by a metal-chalcogenide cluster directly anchored onto
the gold surface through core ligands and offers a simple way to prepare a new
class of functionalized inorganic monolayers.
PMID- 17028708
TI - An improved method for the computation of ligand steric effects based on solid
angles.
AB - An improved algorithm has been designed to characterize ligand interactions in
organometallic and coordination complexes in terms of the percentage of the metal
coordination sphere shielded by a given ligand. The computations for ligand solid
angles are performed numerically and employ introduced atomic radii that are
larger than covalent but smaller than van der Waals radii. This approach enables
facile evaluation of steric congestion in the metal coordination sphere,
quantification of unfavorable interligand contacts, and in some cases prediction
of the complex composition or ligand coordination on purely geometrical grounds.
PMID- 17028709
TI - Basicity and coordination properties of a new phenanthroline-based bis
macrocyclic receptor.
AB - The synthesis and characterisation of the new macrocyclic ligand 6-methyl-2,6,10
triaza-[11]-12,25-phenathrolinophane (L1), which contains a triamine aliphatic
chain linking the 2,9 positions of 1,10-phenanthroline and of its derivative L2,
composed by two L1 moieties connected by an ethylenic bridge, are reported. Their
basicity and coordination properties toward Cu(II), Zn(II), Cd(II), Pb(II) and
Hg(II) have been studied by means of potentiometric and spectroscopic (UV-Vis,
fluorescence emission) measurements in aqueous solutions. L1 forms 1:1 metal
complexes in aqueous solutions, while L2 can give both mono- and dinuclear
complexes. In the mononuclear L2 complexes the metal is sandwiched between the
two cyclic moieties. The metal complexes with L1 and L2 do not display
fluorescence emission, due to the presence of amine groups not involved in metal
coordination. These amine groups can quench the excited fluorophore through an
electron transfer process. The ability of the Zn(II) complexes with L1 and L2 to
cleave the phosphate ester bond in the presence has been investigated by using
bis(p-nitrophenyl)phosphate (BNPP) as substrate. The dinuclear complex with L2
shows a remarkable hydrolytic activity, due to the simultaneous presence within
this complex of two metals and two hydrophobic units. In fact, the two Zn(II) act
cooperatively in substrate binding, probably through a bridging interaction of
the phosphate ester; the interaction is further reinforced by pi-stacking pairing
and hydrophobic interactions between the phenanthroline unit(s) and the p
nitrophenyl groups of BNPP.
PMID- 17028710
TI - Syntheses and reactivity studies of solvated dirhenium acetonitrile complexes.
AB - Fully and partially solvated triply-bonded [Re2]4+ complexes have been
synthesized and their X-ray structures are described. A fully solvated dirhenium
salt with BArf [tetrakis(3,5-bis(trifluoromethyl)phenyl)borate] as the counter
anion [Re2(CH3CN)10][BArf]4 () has been characterized. The solubility of the
complex in CH2Cl2 and THF in addition to CH3CN offers the possibility of improved
reactivity. The structure of [Re2(micro-O)(CH3CN)10][BF4]4 () that possesses a
linear [Re(III)-O-Re(III)]4+ unit is reported. Protonation reactions of cis
Re2Cl2(dppm)2(O2CCH3)2 and trans-Re2Cl4(dppm)2 with HBF4.Et2O in acetonitrile
afforded cis and trans [Re2(dppm)2(CH3CN)6][BF4]4 ( and ), respectively.
Prolonging the reaction time, however, does not lead to fully solvated complex
[Re2(CH3CN)10][BF4]4. The neutral nitrogen donor ligands pynp (2-(2-pyridyl)-1,8
naphthyridine) and tznp (2-(2-thiazolyl)-1,8-naphthyridine) react readily with
[Re2(CH3CN)10][BF4]4 to provide trans-[Re2(pynp)2(CH3CN)4][BF4]4 and trans
[Re2(tznp)2(CH3CN)4][BF4]4. The X-ray structures trans-[Re2(pynp)2(CH3CN)4][BF4]4
() and trans-[Re2(tznp)2(CH3CN)4][BF4]3[PF6] () have been determined.
PMID- 17028711
TI - Effects of multiple ion loading on redox and luminescence properties of ruthenium
trisphenanthroline crown ether hybrids.
AB - Homoleptic and heteroleptic ruthenium trisphenanthrolines were prepared with
azacrown ethers attached to the 4,7-positions of the phenanthrolines to maximise
the electronic communication between the ruthenium and the crown ethers as
complexation sites. Redox and spectral data were processed to explain the non
steady trends in the absorption and emission spectra in the series. Addition of
Ba2+ entailed large shifts in the redox potential (up to 370 mV) and in the
emission spectra (up to 87 nm). Due to the crowded situation of the azacrown
ether units in, this complex showed a non-linear behaviour both in the redox and
emission properties upon loading with Ba2+ that is postulated to originate from
the intermediate formation of sandwich type complexes.
PMID- 17028712
TI - Solution chemistry of 1,15-bis(N,N-dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15
pentaazapentadecane with metal ions of biological interest-Insights toward active
metal ion containing therapeutics and diagnostic agents.
AB - The equilibrium constants of Cu(II), Zn(II), Ca(II) and Gd(III) with 1,15-bis(N,N
dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15-pentaazapentadecane (La) have been
studied at 25 degrees C and an ionic strength of 0.15 mol dm-3. Copper forms more
stable complexes with La than the other metal ions investigated. This is probably
due to the ease with which Cu(II) deprotonates the nitrogen donor atoms of the
amide groups. UV/Vis spectrophotometric data indicate tetradentate binding of the
ligand towards copper in [CuLaH-1] and pentadentate binding in [CuLaH-2]. Octanol
water partition coefficients of Cu(II)-La complexes indicate that although these
species are largely hydrophilic, approximately 5.62% of the [CuLaH-1] complex
goes into the organic phase. This percentage may promote dermal absorption of
copper with a calculated penetration rate of 3.75x10(-4) mm h-1. The [CuLaH-1]
species which predominates at pH 7.4 is a poor mimic of native copper-zinc
superoxide dismutase. Blood-plasma simulation studies predict that La is unable
to increase the low molecular mass copper fraction in vivo. This has been
confirmed by biodistribution patterns, which are similar to those of 64CuCl2.
PMID- 17028713
TI - Synthesis and properties of Rh(I) and Ir(I) distibine complexes with
organometallic co-ligands.
AB - The first series of Rh(I) distibine complexes with organometallic co-ligands is
described, including the five-coordinate [Rh(cod)(distibine)Cl], the 16-electron
planar cations [Rh(cod)(distibine)]BF4 and [Rh{Ph2Sb(CH2)3SbPh2}2]BF4 and the
five-coordinate [Rh(CO)(distibine)2][Rh(CO)2Cl2] (distibine=R2Sb(CH2)3SbR2, R=Ph
or Me, and o-C6H4(CH2SbMe2)2). The corresponding Ir(I) species
[Ir(cod)(distibine)]BF4 and [Ir{Ph2Sb(CH2)3SbPh2}2]BF4 have also been prepared.
The complexes have been characterised by 1H and 13C{1H} NMR and IR spectroscopy,
electrospray mass spectrometry and microanalysis. The crystal structure of the
anion exchanged [Rh(CO){Ph2Sb(CH2)3SbPh2}2]PF(6).3/4CH2Cl2 is also described. The
methyl-substituted distibine complexes are less stable than the complexes of
Ph2Sb(CH2)3SbPh2, with C-Sb fission occurring in some of the complexes of the
former. The salts [Rh(CO){Ph2Sb(CH2)3SbPh2}2]PF6 and [Rh{Ph2Sb(CH2)3SbPh2}2]BF4
undergo oxidative addition with Br2 to give the known
[RhBr2{Ph2Sb(CH2)3SbPh2}2]+, while using HCl gives the same hydride complex from
both precursors, which is tentatively assigned as [RhHCl2{Ph2Sb(CH2)3SbPh2}]. An
unexpected further Rh(III) product from this reaction, trans
[RhCl2{Ph2Sb(CH2)3SbPh2}{PhClSb(CH2)3SbClPh}]Cl, was identified by a crystal
structure analysis and represents the first structurally characterised example of
a chlorostibine coordinated to a metal. [Rh{Ph2Sb(CH2)3SbPh2}2]BF4 reacts with CO
to give [Rh(CO){Ph2Sb(CH2)3SbPh2}2]BF4 initially, and upon further exposure this
species undergoes further reversible carbonylation to give a cis-dicarbonyl
species thought to be [Rh(CO)2{Ph2Sb(CH2)3SbPh2}{kappa1Sb-Ph2Sb(CH2)3SbPh2}]BF4
which converts back to the monocarbonyl complex when the CO atmosphere is
replaced with N2.
PMID- 17028714
TI - Syntheses and structural characterizations of 24-membered dimetal (Mn, Ni, Fe)
macrocyclic complexes and the C-S bond formation between acetylacetone and a
mercapto N-heterocycle.
AB - An organic ligand 2,5-di(3-pentanedionylthio)-1,3,4-thiadiazole (H2L) reacts with
metal (Mn, Ni, Fe) salts, resulting in 24-membered dimetal macrocyclic complexes
[MnL(H2O)(dmso)](2).2dmso, [NiL(H2O)(dmf)](2).2dmf, [MnL(dmf)2]2 and
[Fe2L2(solvent)2(SO4)] (solvent=dmso; H2O ; dmf). Di-manganese macrocyclic
complexes [MnL(dmf)(dmso)]2 and [MnL(H2O)2](2).6H2O can also be obtained directly
by aerobic assembly reaction of MnCl2, dipotassium 1,3,4-thiadiazole-2,5
dithiolate (K2tdadt) and acetylacetone (H2acac) in various solvents, accompanying
a C-S bond formation between acetylacetone and the mercapto N-heterocycle.
Disulfide has been considered as the intermediate in the assembly reaction.
Meanwhile an assembly reaction including MnCl2, 2-mercaptobenzimidazole and
H2acac has produced an organic compound 2-(3-pentanedionylthio)benzimidazole with
a new C-S bond. These dimetal complexes have similar macrocyclic structures, in
which solvent molecules and sulfate coordinate to the octahedral metal in trans
configuration, whereas a pair of water molecules are located in octahedral cis
positions for owing to a small steric effect. A host cavity of sufficiently large
size exists in the macrocyclic structure to trap the solvent molecules and the
sulfate anion. The IR spectra have been used to assign the solvent molecules
trapped and the sulfate anion which is shown as a bridged bidentate ligand.
Thermal analyses show the stability of the macrocyclic backbone below 200 degrees
C and gradual release processes of the trapped solvent molecules. Decomposition
and oxidation of the dimetal macrocycle backbone occur at 300-500 degrees C,
resulting in a metal sulfate. Further decomposition led to metal oxide at 500-600
degrees C.
PMID- 17028715
TI - o-Phenylene-bridged Cp/sulfonamido titanium complexes for ethylene/1-octene
copolymerization.
AB - The Suzuki-coupling reaction of 2-(dihydroxyboryl)-3,4-dimethyl-2-cyclopenten-1
one and 2-(dihydroxyboryl)-3-methyl-2-cyclopenten-1-one with 2-bromoaniline
derivatives affords cyclopentenone compounds from which cyclopentadiene
compounds, 4,6-R'(2)-2-(2,5-Me2C5H3)C6H2NH2 and 4,6-R'(2)-2-(2,3,5
Me3C5H2)C6H2NH2 are prepared. After sulfonation of the -NH2 group with p-TsCl,
metallation is carried out by successive addition of Ti(NMe2)4 and Me2SiCl2
affording o-phenylene-bridged Cp/sulfonamido titanium dichloride complexes, [4,6
R'(2)-2-(2,5-Me2C5H2)C6H2NSO2C6H4CH3)]TiCl2 (R'=H, ; R'=Me, ; R'=F, ) and [4,6
R'(2)-2-(2,3,5-Me3C5H)C6H2NSO2C6H4CH3)]TiCl2 (R'=H, ; R'=Me, ; R'=F, ). The
molecular structures of and [2-(2,5-Me2C5H2)C6H4NSO2C6H4CH3)]Ti(NMe2)2 are
determined by X-ray crystallography. The Cp(centroid)-Ti-N angle in is smaller
(100.90 degrees) than that observed for the CGC (constrained-geometry catalyst),
[Me2Si(eta5-Me4Cp)(NtBu)]TiCl2 (107.6 degrees) indicating a more "constrained
feature" in than in the CGC. Complex shows the highest activity among the newly
prepared complexes in ethylene/1-octene copolymerization but it is slightly
inferior to the CGC in terms of activity, comonomer-incorporation ability, and
molecular weight of the obtained polymers.
PMID- 17028717
TI - Single molecule studies of DNA binding proteins using optical tweezers.
AB - Optical tweezers have become a versatile tool in the biological sciences.
Combined with various types of optical microscopy, they are being successfully
used to discover the fundamental mechanism of biological processes. Recently, the
study of proteins acting on DNA was aggressively undertaken at the single
molecule level. Here, we review the most recent studies which have revealed the
dynamic behavior of individual protein molecules at work on DNA, providing
detailed mechanistic insight that could not be revealed, at least not easily,
using bulk-phase or ensemble approaches.
PMID- 17028719
TI - Evaluation of capillary ion exchange stationary phase coating distribution and
stability using radial capillary column contactless conductivity detection.
AB - The use of radial (across) capillary column capacitively coupled contactless
conductivity detection is demonstrated as a simple and rapid technique for
visualisation of stationary phase longitudinal coverage and coating stability in
capillary ion exchange chromatography.
PMID- 17028718
TI - Metabolic fingerprinting in disease diagnosis: biomedical applications of
infrared and Raman spectroscopy.
AB - The ability to diagnose the early onset of disease, rapidly, non-invasively and
unequivocally has multiple benefits. These include the early intervention of
therapeutic strategies leading to a reduction in morbidity and mortality, and the
releasing of economic resources within overburdened health care systems. Some of
the routine clinical tests currently in use are known to be unsuitable or
unreliable. In addition, these often rely on single disease markers which are
inappropriate when multiple factors are involved. Many diseases are a result of
metabolic disorders, therefore it is logical to measure metabolism directly. One
of the strategies employed by the emergent science of metabolomics is metabolic
fingerprinting; which involves rapid, high-throughput global analysis to
discriminate between samples of different biological status or origin. This
review focuses on a selective number of recent studies where metabolic
fingerprinting has been forwarded as a potential tool for disease diagnosis using
infrared and Raman spectroscopies.
PMID- 17028720
TI - Sensitive and rapid electrochemical bioassay of glycosidase activity.
AB - Here we present a highly sensitive, rapid and simple electrochemical assay for
glycosidases based on treatment of the glycosidase with the appropriate p
nitrophenyl glycoside and anodic detection of released p-nitrophenol. The
attractive characteristics of the new bioassay should facilitate advanced
glycomic research and routine clinical diagnostics since glycosidases are
associated with various diseases.
PMID- 17028721
TI - Layer guided-acoustic plate mode biosensors for monitoring MHC-peptide
interactions.
AB - The transduction signals from the immobilisation of a class I heavy chain, HLA
A2, on a layer guided acoustic plate mode device, followed by binding of beta(2)
microglobulin and subsequent selective binding of a target peptide are reported.
PMID- 17028723
TI - Apparent 'electrocatalytic' activity of multiwalled carbon nanotubes in the
detection of the anaesthetic halothane: occluded copper nanoparticles.
AB - The electrocatalytic detection of the anaesthetic halothane on a multiwalled
carbon nanotube modified glassy carbon electrode is reported with a low limit of
detection of 4.6 microM. A thorough investigation of the underlying cause of this
apparent catalytic effect is undertaken by comparing the response of various
carbon electrodes including glassy carbon, basal- and edge-plane pyrolytic
graphite electrodes (bppg and eppg respectively) to increasing additions of
halothane. The reduction of halothane is shifted by 250-300 mV to more negative
potentials at an eppg electrode than that observed at the GC-CNT electrode.
Therefore the results of this investigation show that, surprisingly, the
electrocatalysis is not solely due to the introduction of edge-plane-like defect
sites on the carbon nanotubes as is commonly found for many other substrates
showing favourable voltammetry at nanotube modified electrodes. Instead, we
reveal that in this unusual case the electroactive sites for the reduction of
halothane are due to the presence of copper nanoparticles occluded within the
carbon nanotubes during their production, which are never completely removed by
standard purification techniques such as acid washing. This is only the third
known case where apparent electrocatalysis by carbon nanotube modified electrodes
is due to occluded metal-related nanoparticles within the nanotube structure,
rather than the active sites being the edge-plane-like defect sites on the
nanotubes. Furthermore this is the first case where the active sites are
nanoparticles of copper metal, rather than metal oxide nanoparticles (namely
oxides of iron(II)/(III)) as was found to be the case in the previous examples.
PMID- 17028722
TI - Selective coulometric release of ions from ion selective polymeric membranes for
calibration-free titrations.
AB - Coulometry belongs to one of the few known calibration-free techniques and is
therefore highly attractive for chemical analysis. Titrations performed by the
coulometric generation of reactants is a well-known approach in electrochemistry,
but suffers from limited selectivity and is therefore not generally suited for
samples of varying or unknown composition. Here, the selective coulometric
release of ionic reagents from ion-selective polymeric membrane materials
ordinarily used for the fabrication of ion-selective electrodes is described. The
selectivity of such membranes can be tuned to a significant extent by the type
and concentration of ionophore and lipophilic ion-exchanger and is today well
understood. An anodic current of fixed magnitude and duration may be imposed
across such a membrane to release a defined quantity of ions with high
selectivity and precision. Since the applied current relates to a defined ion
flux, a variety of non-redox active ions may be accurately released with this
technique. In this work, the released titrant's activity was measured with a
second ionophore-based ion-selective electrode and corresponded well with
expected dosage levels on the basis of Faraday's law of electrolysis. Initial
examples of coulometric titrations explored here include the release of calcium
ions for complexometric titrations, including back titrations, and the release of
barium ions to determine sulfate.
PMID- 17028724
TI - An electronic DNA microarray technique for detection and differentiation of
viable Campylobacter species.
AB - An electronic oligonucleotide microarray technique was developed for detection
and differentiation of the viable Campylobacter species, C. jejuni, C. coli, and
C. lari. This development consisted of four major components: identification of
single nucleotide polymorphisms (SNPs) within the hsp60 gene as species markers,
design of fluorescently labelled SNP-based reporters, development of an
electronic microarray detection, and application of the integrated technique to
analysis of Campylobacter species in food samples. A unique capability of this
technique is the specific detection of viable cells and not dead ones. This is
achieved by using mRNA of the 60 kDa heat-shock protein as the viability marker.
The identification of two unique SNPs closely located at positions 291 and 294 of
the hsp60 gene enabled the differentiation of the three Campylobacter species.
This technique was able to detect as few as two viable Campylobacter cells. The
analysis of 19 blind Campylobacter samples showed 100% agreement with their
identities obtained using pulsed-field gel electrophoresis. The analysis of six
chicken samples revealed the presence of C. coli in one of the samples.
PMID- 17028725
TI - A compact broadband cavity enhanced absorption spectrometer for detection of
atmospheric NO(2) using light emitting diodes.
AB - A compact and low power detector has been developed for the in situ measurement
of atmospheric NO(2) using broadband cavity enhanced absorption spectroscopy.
Absorption by the O(2)-O(2) collisional pair was used to determine the cavity
mirror reflectivity, thus enabling the retrieval of absolute absorber
concentrations by differential spectral fitting techniques. Quantitative amounts
of ambient NO(2) (between 3 and 32 parts per billion) were retrieved from spectra
recorded in the presence of ambient aerosol with statistical uncertainties
approaching 100 ppt for a 60 s averaging period. The instrument's response was
compared to that of a commercial chemiluminescence detector and was found to
agree to within 6%.
PMID- 17028726
TI - Subfemtomolar electrochemical detection of target DNA by catalytic enlargement of
the hybridized gold nanoparticle labels.
AB - After showing the failure of conventional gold-enhancement procedures to amplify
the gold nanoparticle-based electrochemical transduction of DNA hybridization in
polystyrene microwells, a new efficient protocol was developed and evaluated for
the sensitive quantification of a 35 base-pair human cytomegalovirus nucleic acid
target (tDNA). In this assay, the hybridization of the target adsorbed on the
bottom of microwells with an oligonucleotide-modified Au nanoparticle detection
probe (pDNA-Au) was monitored by the anodic stripping detection of the chemically
oxidized gold label at a screen-printed microband electrode (SPMBE). Thanks to
the combination of the sensitive Au(III) determination at a SPMBE with the large
amount of Au(III) released from each pDNA-Au, picomolar detection limits of tDNA
can be achieved. Further enhancement of the hybridization signal based on the
autocatalytic reductive deposition of ionic gold (Au(III)) on the surface of the
gold nanoparticle labels anchored on the hybrids was first envisaged by
incubating the commonly used mixture of Au(III) and hydroxylamine (NH(2)OH).
However, due to a considerable nonspecific current response of poor
reproducibility it was not possible to significantly improve the analytical
performances of the method under these conditions. Complementary transmission
electronic microscopy experiments indicated the loss of most of the grown gold
labels during the post-enlargement rinsing step. To circumvent this drawback, a
polymeric solute containing polyethyleneglycol and sodium chloride was introduced
in the growth media to act as an aggregating agent during the catalytic process
and thus retain the enlarged labels on the bottom of the microwell. This
strategy, which led to an efficient increase of the hybridization response,
allowed detection of tDNA concentrations as low as 600 aM (i.e., 10(4) lower than
without amplification), and thus offers great promise for ultrasensitive
detection of other hybridization events.
PMID- 17028727
TI - Use of microchip-based hydrodynamic focusing to measure the deformation-induced
release of ATP from erythrocytes.
AB - In order to understand the role that erythrocytes play in conditions such as
pulmonary hypertension, in vitro mimics of the microcirculation are needed. This
paper describes the use of microchip-based hydrodynamic focusing to develop a
mimic that allows both mechanical deformation of erythrocytes and quantification
of the adenosine triphosphate (ATP) that is subsequently released in response to
this deformation. In this mimic, two sheathing streams of a luciferin/luciferase
mixture are used to focus and deform a central fluid flow of an erythrocyte
sample. The focusing width is changed by simply manipulating the sheath flow
rate. This allows a variety of cross-sectional areas to be studied using single
point chemiluminescent detection. It was shown that increasing the sheath flow
rate does result in elevated levels of ATP release. For example, one sample of
rabbit erythrocytes released 0.80 (+/- 0.13) microM ATP when focused to a cross
section of 3480 microm(2), while focusing the same sample to a smaller cross
section (1160 microm(2)) led to a release of 6.43 (+/- 0.40) microM ATP. In
addition, two different inhibitors, diamide and glibenclamide, were used to
ensure a lack of cell lysis. This approach can be used to examine a wide range of
deformation forces in a high throughput fashion and will be of interest to
researchers studying the mechanisms leading to vasodilation in the
microvasculature.
PMID- 17028728
TI - Novel integrated paired emitter-detector diode (PEDD) as a miniaturized
photometric detector in HPLC.
AB - A novel low power, low cost, highly sensitive, miniaturized light emitting diode
(LED) based flow detector has been used as optical detector for the detection of
sample components in high performance liquid chromatography (HPLC). This
colorimetric detector employs two LEDs, one operating in normal mode as a light
source and the other is reverse biased to work as a light detector. Instead of
measuring the photocurrent directly, a simple timer circuit is used to measure
the time taken for the photocurrent generated by the emitter LED (lambda(max) 500
nm) to discharge the detector LED (lambda(max) 621 nm) from 5 V (logic 1) to 1.7
V (logic 0) to give digital output directly without using an A/D converter.
Employing a post-column reagent method, a Nucleosil 100-7 column (functionalized
with iminodiacetic acid (IDA) groups) was used to separate a mixture of
transition metal complexes, manganese(II) and cobalt(II) in 4-(2-pyridylazo)
resorcinol (PAR). All optical measurements were taken by using both the in-built
HPLC variable wavelength detector and the proposed paired-emitter-detector-diode
(PEDD) optical detector configured in-line for data comparison. The concentration
range investigated using the PEDD was found to give a linear response to the
Mn(II) and Co(II) PAR complexes. The effects of flow rate and emitter LED light
source intensity were investigated. Under optimised conditions the PEDD detector
offered a linear range of 0.9-100 microM and LOD of 0.09 microM for Mn-PAR
complex. A linear range of 0.2-100 microM and LOD of 0.09 microM for Co-PAR
complex was achieved.
PMID- 17028729
TI - Rapid electrophoretic separations in short capillaries using contactless
conductivity detection and a sequential injection analysis manifold for
hydrodynamic sample loading.
AB - A sequential injection-capillary electrophoresis (SI-CE) system for the fast and
automated quantitative analysis of anions and cations is described. Because of
the low sample load in capillary electrophoresis a split injection approach had
to be used to achieve reliable hydrodynamic injection. The use of a capillary of
8 cm effective length allowed for the separation of five inorganic cations within
11 s. One common electrolyte solution containing 12 mM l-histidine and 2 mM 18
crown-6 whose pH value was adjusted to 4.0 with 10% v/v acetic acid was used for
anions and cations, thus the analysis of both groups of analytes could be carried
out in rapid sequence simply by switching the polarity of the high voltage
supply. The system also allows automated flushing of the capillary. Detection
limits between about 2 and 5 micromol l(-1) could be achieved with the
contactless conductivity detector employed.
PMID- 17028730
TI - Template-free routes to porous inorganic materials.
AB - New approaches to solid-state reactivity have allowed us to develop unusual
routes to porous inorganic materials. This article describes our recent work on
template-free routes involving the selective leaching of one phase from a two
phase composite to form porous oxides. Subsequent reactions have been developed
to yield porous metals, conformal coatings, and hierarchically porous materials.
Pores can also be generated through simple redox processes in transition-metal
oxides; such redox cycling allows mesopores to be produced in a regenerative
process in a material which is already macroporous.
PMID- 17028731
TI - Two new 3D metal-organic frameworks of nanoscale cages constructed by Cd(II) and
conformationally-flexible cyclohexanehexacarboxylate.
AB - Hydrothermal reactions of Cd(NO3)2.4H2O with a,e,a,e,a,e-1,2,3,4,5,6
cyclohexanehexacarboxylic acid (H6L(I)) generate two new 3D MOFs with nanoscale
cages, in which the L(I) ligand in the first MOF transforms its conformation to
the e,e,e,e,e,e form while the L(I) ligand in the second MOF transforms its
conformation to mixed e,e,e,e,e,e and e,e,e,e,a,a forms in a 1 : 3 ratio, showing
the effect of the auxiliary sodium ion on stabilizing the intermediate
conformations and on the construction of the heterometallic MOF structure.
PMID- 17028732
TI - Chiral polymers by iterative tandem catalysis.
AB - Racemic omega-substituted caprolactones can be completely converted into chiral
polyesters of remarkable MW and high ee by combining lipase-catalyzed ring
opening polymerization with Ru-catalyzed racemization.
PMID- 17028733
TI - A lanthanide metal-organic framework with high thermal stability and available
Lewis-acid metal sites.
AB - A lanthanide metal-organic framework, Dy(BTC)(H2O).DMF, with excellent thermal
stability shows a high surface area, 655 m(2) g(-1), high hydrogen and carbon
dioxide storage capability, and available Lewis-acid metal sites which could be
anticipated to use in catalysis and metal-site specific chemical sensor.
PMID- 17028734
TI - Metal-mediated coordination polymer nanotubes of 5,10,15,20-tetrapyridylporphine
and tris(4-pyridyl)-1,3,5-triazine at the water-chloroform interface.
AB - Coordination polymer nanotubes have been prepared by using the Hg2+-mediated co
assembly of two ligands, tetrapyridylporphine (TPyP) and tris(4-pyridyl)-1,3,5
triazine (TPyTa), at the water-chloroform interface.
PMID- 17028735
TI - Unique gold chemoselectivity for the aerobic oxidation of allylic alcohols.
AB - Gold nanoparticles supported on nanocrystalline ceria has been found to be more
active and chemoselective than palladium and gold(core)-palladium(shell)
nanoparticles for the aerobic oxidation of allylic alcohols.
PMID- 17028736
TI - Tetranuclear Cu(II) complex supported by a central mu4-1,1,3,3 azide bridge.
AB - The new cluster [Cu4L2(N3)]Cl.16H2O has been synthesized and characterized; it
features a unique mu4-1,1,3,3 bridging mode for azide, whose capacity to mediate
magnetic coupling has been examined through bulk magnetic measurements and
numeric fitting procedures.
PMID- 17028737
TI - Easy access to stable pentavalent uranyl complexes.
AB - Reaction of UO2I2(THF)3 with 1 molar equivalent of KC5R5 (R = H, Me) in pyridine
led to the uranyl(V) compound {[UO2(Py)5][KI2(Py)2]}(infinity), which is an
infinite 1D polymer in its crystalline form; the UO2X(THF)n (X = I, OSO2CF3)
complexes were obtained by reduction of their U(VI) parents with TlC5H5 or KC5R5
in THF.
PMID- 17028738
TI - Rhodium-catalyzed carbonylative arylation of alkynes with arylboronic acids: an
efficient and straightforward method in the synthesis of 5-aryl-2(5H)-furanones.
AB - 5-Aryl-2(5H)-furanones can be synthesized by the Rh-catalyzed reactions of
arylboronic acids with internal alkynes under a CO atmosphere.
PMID- 17028739
TI - The intramolecular beta-fluorine...ammonium interaction in 4- and 8-membered
rings.
AB - The structures of 3-fluoroazetidinium hydrochloride and 3-fluoro-1,5
diazacyclooctane hydrobromide are explored both by X-ray diffraction analysis and
DFT calculations, and the conformations of these molecules are shown to be
significantly influenced by the through space C-F...N+ interaction.
PMID- 17028740
TI - The chemical modification of liposome surfaces via a copper-mediated [3 + 2]
azide-alkyne cycloaddition monitored by a colorimetric assay.
AB - A generic method for the efficient in-situ modification of liposomes is described
based on "click" chemistry, and a simple colorimetric assay is developed for
monitoring the reaction.
PMID- 17028741
TI - Formation of triple helical nanofibers using self-assembling chiral benzene-1,3,5
tricarboxamides and reversal of the nanostructure's handedness using mirror image
building blocks.
AB - Intertwining triple helical nanofibers with an overall handedness have been
formed from self-assembling chiral benzene-1,3,5-tricarboxamides , and , whereas
the achiral benzene-1,3,5-tricarboxamide upon self-association gives rise to
straight nanofibers without any twist and transmission electron microscopy images
of chiral compounds clearly demonstrate that the handedness of the triple helical
nanofibers can be reversed by using the enantiomeric benzene-1,3,5-tricarboxamide
building blocks.
PMID- 17028742
TI - Anion binding inhibition of the formation of a helical organogel.
AB - A chiral tris(urea) organogelator gels dmso-water and methanol-water mixtures at
low weight percent. The formation of the helical gel fibres is partially
inhibited by addition of chloride, which is bound by the gelator, resulting in
fully crystalline material characterised by X-ray crystallography.
PMID- 17028743
TI - Tuning electron transfer through p-phenyleneethynylene molecular wires.
AB - Weak wire-like behavior-with a damping factor (beta) of 0.2 +/- 0.05 A(-1)--has
been found in a series of C60-wire-exTTF systems (i.e., p-phenyleneethynylene):
these results contrast with previous observations involving p-phenylenevinylene
systems.
PMID- 17028744
TI - Ultrasensitive detection of DNA by the PCR-Induced generation of DNAzymes: the
DNAzyme primer approach.
AB - The ultrasensitive detection of DNA is achieved by PCR-induced evolution of a
DNAzyme.
PMID- 17028745
TI - New reactivity and structural insights of alkali-metal-mediated alumination in
directed ortho-alumination of a tertiary aromatic amide.
AB - The first reported sodium alkyl(TMP)aluminate reagent to be synthesised and
crystallographically characterised, [TMEDA.Na(mu-TMP)(mu-(I)Bu)Al((I)Bu)2],
reacts as an amido base towards phenylacetylene to form crystalline
[(TMEDA)2.Na(mu-CCPh)(mu-(I)Bu)Al((I)Bu)2]; whereas the congeneric TMEDA
stabilised lithium (TMP)aluminate exhibits dual alkyl/amido basicity in its
reaction with N,N-diisopropylbenzamide to form a novel heterobimetallic
heterotrianionic crystalline complex [{PhC(=O)N(iPr)2}.Li{2-[1
C(=O)N(iPr)2]C6H4}{Me2NCH2CH2N(Me)CH2}Al(iBu)2], which, in addition to having an
ortho-deprotonated benzamide ligand, also contains a methyl-deprotonated TMEDA
ligand and a neutral benzamide molecule ligated to lithium.
PMID- 17028746
TI - A highly selective, organocatalytic route to chiral 1,2-oxazines from ketones.
AB - A sequential, organocatalysed asymmetric reaction to access chiral 1,2-oxazines
from achiral ketone starting materials is reported, which proceeds in moderate to
good yields and excellent enantioselectivity.
PMID- 17028747
TI - Accessing tetrahydrofuran-based natural products by microbial Baeyer-Villiger
biooxidation.
AB - A heterobicyclic lactone obtained by stereoselective Baeyer-Villiger biooxidation
with recombinant whole-cells expressing cyclopentanone monooxygenase from
Comamonas sp. NCIMB 9872 was used for formal total syntheses of various natural
products containing a tetrahydrofuran structural motif.
PMID- 17028748
TI - Molecularly-imprinted polymeric logic gates selective for predetermined chemical
input species.
AB - Selective AND and OR logic gates were fabricated by molecular imprinting with
simultaneous use of two kinds of template species, with the resultant binding
behaviour (AND or OR) of the imprinted polymers governed by intermolecular
interactions between the two template species.
PMID- 17028749
TI - Multilayer films based on host-guest interactions between biocompatible polymers.
AB - Multilayer films are formed using host-guest interaction between two derivatized
chitosans, one, with beta-cyclodextrin cavities and the other with adamantyl
moieties.
PMID- 17028750
TI - Site-specific transition of cytosine to uracil via reversible DNA photoligation.
AB - We report that deamination coupled with 5-carboxyvinyldeoxyuridine-mediated
photobranching causes the heat-induced transition of cytosine to uracil with high
efficiency without any side reaction.
PMID- 17028751
TI - 3-Hydroxypyrrolidines from epoxysulfonamides and dimethylsulfoxonium methylide.
AB - N-Tosyl-protected 3-hydroxypyrrolidines are prepared by reaction of
dimethylsulfoxonium methylide with readily available epoxysulfonamides.
PMID- 17028752
TI - Selection of DNA ligands for protein kinase C-delta.
AB - Protein kinase Cs are a family of serine and threonine kinases that mediate a
wide variety of cellular signalling processes such as cell growth,
differentiation, apoptosis and tumor development. We have selected high-affinity
DNA aptamers for PKCdelta by capillary electrophoresis based SELEX (systematic
evolution of ligands by exponential enrichment, CE-SELEX). We have demonstrated
that fluorescently tagged PB9 aptamer can specifically recognize PKCdelta under
in vitro conditions. The Kd of the aptamer-protein binding is 122 nM. These
aptamers will enable us to apply fluorescently labelled probes to study the
spatiotemporal dynamics and activation of individual endogenous PKC isoforms
during various cell signalling processes.
PMID- 17028753
TI - An outstanding catalyst for asymmetric transfer hydrogenation in aqueous solution
and formic acid/triethylamine.
AB - A Rh/tetramethylcyclopentadienyl complex containing a tethered functionality has
been demonstrated to give excellent results in the asymmetric transfer
hydrogenation of ketones in both aqueous and formic acid/triethylamine media.
PMID- 17028754
TI - Addressing the regioselectivity problem in organic synthesis.
AB - A screening process uncovered a heterogeneous catalytic system that hydrolyzes
one of two nearly identical ketals in several diketals with a high selectivity.
PMID- 17028755
TI - A new and convenient method for the synthesis of strong non-ionic bases.
AB - Various strong non-ionic phosphazene bases were obtained by a new, efficient and
very simple method involving the lithium phosphonium azayldiide Ph3P=NLi as a
precursor.
PMID- 17028756
TI - Discrete copper(I) clusters with Cu6P6Se6 and Cu6P4Se6 cores.
AB - The reactions of chalcogenophosphinites with copper(I) metal salts are shown to
yield highly stable, multi-metallic copper-chalcogen based clusters with novel
topologies.
PMID- 17028757
TI - Synthesis of the ester side chains of some potently antileukemic harringtonia
alkaloids from chiral citrates.
AB - The selective reduction of one of the three carboxyl groups of two chiral citric
acid derivatives to the corresponding aldehydes, under Rosenmund conditions, are
reported together with the application of these aldehydes to the syntheses of the
ester side chains of some potently antileukemic Cephalotaxus alkaloids e.g.
anhydroharringtonine.
PMID- 17028758
TI - A transmembrane anion transporter selective for nitrate over chloride.
AB - The C3-symmetric triamide selectively transports NO3- anions across lipid
vesicles: this H+-NO3- co-transporter alters the pH inside of liposomes
experiencing a NO3-/Cl- gradient.
PMID- 17028759
TI - Pallado-catalysed hydrophosphination of alkynes: access to enantio-enriched P
stereogenic vinyl phosphine-boranes.
AB - Preliminary results dealing with the synthesis of non-racemic P-stereogenic
vinylphosphine-boranes by hydrophosphination of alkynes in the presence of a
chiral catalyst are reported.
PMID- 17028760
TI - Kinetic and thermodynamic parameters for the equilibrium reactions of phenols
with the dpph. radical.
AB - The kinetics and energetics of the reversible reaction of phenols with the dpph.
radical have been studied; steric shielding of the divalent N by the o-NO2 in
dpph. seems to be the main cause of the entropic barriers of this reaction.
PMID- 17028761
TI - Sodium intake in very low birth weight infants: is more always better?
PMID- 17028762
TI - The Latin American exception: why is childhood asthma so prevalent in Brazil?
PMID- 17028763
TI - We need to predict extubation failure.
PMID- 17028764
TI - Cockroach allergy: risk factor for asthma severity.
PMID- 17028766
TI - Serum prevalence of celiac disease in children and adolescents with type 1
diabetes mellitus.
PMID- 17028768
TI - Pediatrics - research and publications.
PMID- 17028769
TI - Antimicrobial properties of alpha-MSH and related synthetic melanocortins.
AB - The natural antimicrobial peptides are ancient host defense effector molecules,
present in organisms across the evolutionary spectrum. Several properties of
alpha-melanocyte stimulating hormone (alpha-MSH) suggested that it could be a
natural antimicrobial peptide. Alpha-MSH is a primordial peptide that appeared
during the Paleozoic era, long before adaptive immunity developed and, like
natural antimicrobial molecules, is produced by barrier epithelia, immunocytes,
and within the central nervous system. alpha-MSH was discovered to have
antimicrobial activity against two representative pathogens, Staphylococcus
aureus and Candida albicans. The candidacidal influences of alpha-MSH appeared to
be mediated by increases in cell cyclic adenosine monophosphate (cAMP). The cAMP
inducing capacity of alpha-MSH likely interferes with the yeast's own regulatory
mechanisms of this essential signaling pathway. It is remarkable that this
mechanism of action in yeast mimics the influences of alpha-MSH in mammalian
cells in which the peptide binds to G-protein-linked melanocortin receptors,
activates adenylyl cyclase, and increases cAMP. When considering that most of the
natural antimicrobial peptides enhance the local inflammatory reaction, the anti
inflammatory and antipyretic effects of alpha-MSH confer unique properties to
this molecule relative to other natural antimicrobial molecules. Synthetic
derivatives, chemically stable and resistant to enzymatic degradation, could form
the basis for novel therapies that combine anti-inflammatory and antimicrobial
properties.
PMID- 17028770
TI - Accuracy of the combination of mammography and sonography in predicting tumor
response in breast cancer patients after neoadjuvant chemotherapy.
AB - BACKGROUND: Residual tumor size after neoadjuvant chemotherapy is an important
consideration in surgical planning. We examined the accuracy of the combination
of mammography and sonography in predicting pathologic residual tumor size.
METHODS: Tumor size was evaluated by physical examination, mammography, and
sonography at diagnosis and before surgery in 162 breast cancer patients who
received neoadjuvant chemotherapy. Agreement between the predicted and the
pathologic responses and the predicted and the pathologic tumor sizes was
calculated. The effect of invasive lobular carcinoma, high nuclear grade, hormone
receptor positivity, and the presence of an extensive intraductal component on
the accuracy of mammography and sonography in predicting pathologic residual
tumor size was analyzed. RESULTS: Forty-two patients (25.9%) had a pathologic
complete response (pCR). Overall agreement between predicted and pathologic
responses was 53% for physical examination, 67% for mammography plus sonography,
and 63% for physical examination plus mammography and sonography. The sensitivity
of mammography and sonography in predicting pCR was 78.6%, and the specificity
was 92.5%; the accuracy was 88.9%. Residual tumor size determined by mammography
and sonography correlated with pathologic residual tumor size (r = .662);
pathologic tumor size was within .5 cm of predicted in 69.1% of patients.
Multivariate analysis showed that pathologic residual tumor size was
underestimated for lobular carcinoma and overestimated for poorly differentiated
tumors. CONCLUSIONS: The combination of mammography and sonography has a high
accuracy in predicting pCR after neoadjuvant chemotherapy. Agreement of residual
tumor size in mammography and sonography with pathologic residual tumor size was
moderate.
PMID- 17028771
TI - Surgical management of symptomatic pericardial effusion in patients with solid
malignancies.
AB - BACKGROUND: Symptomatic pericardial effusion in patients with cancer may lead to
a life-threatening event that requires diligent treatment, but the best surgical
treatment is still controversial. The purpose of this study was to identify
predictors of survival for patients with solid malignancies and symptomatic
pericardial effusion, which might help to select the best surgical treatment for
each patient. METHODS: We retrospectively analyzed 47 patients with solid
malignancies concomitant with symptomatic pericardial effusion who underwent
surgery between 1994 and 2004. Overall survival was calculated from date of
surgery, and prognostic importance of clinical and pathological variables was
assessed. RESULTS: The most common primary sites of disease were breast (46.8%)
and lung (25.6%). Initial pericardiocentesis were performed in 29 patients;
median volume of fluid drained was 480 mL. Median interval from the diagnosis of
primary cancer to the development of pericardial effusion (pericardial effusion
free interval) was 34.8 months. Definitive surgical treatment was performed in 43
patients, as follows: subxiphoid pericardial window (n = 21); thoracotomy and
pleuropericardial window (n = 10); pericardiodesis (n = 8); and
videothoracoscopic pleuropericardial window (n = 4). Pericardiocentesis was the
only procedure in four patients. Median follow-up was 2.9 months. Median overall
survival was 3.7 months. Pericardial effusion-free interval longer than 35 months
and more than 480 mL of fluid drained at initial pericardiocentesis were
determinants of better survival. CONCLUSIONS: Pericardial window and
pericardiodesis seem to be safe and efficacious in treating effusion of the
pericardium. Pericardial effusion-free interval and volume drained at initial
pericardiocentesis are determinants of outcome.
PMID- 17028772
TI - Risk factors for non-sentinel lymph node metastases in patients with breast
cancer. The outcome of a multi-institutional study.
AB - BACKGROUND: In this multi-institutional prospective study, we evaluated whether
we could identify risk factors predictive for non-sentinel lymph node (non-SN)
metastases in breast cancer patients with a positive sentinel lymph node (SN).
METHODS: In this multi-institutional study, 541 eligible breast cancer patients
were included prospectively. RESULTS: The occurrence of non-SN metastases was
related to the size of the SN metastasis (P = .02), primary tumor size (P =
.001), and lymphovascular invasion (P = .07). The adjusted odds ratio was 3.1 for
SN micro-metastasis compared with SN isolated tumor cells, 4.0 for SN macro
metastasis versus SN isolated tumor cells, 3.1 for tumor size (>3.0 cm compared
with =3.0 cm), and 2.0 for lymphovascular invasion (yes versus no). There were
no positive non-SNs when the primary tumor size was =1.0 cm (n = 24) [95%
confidence interval (95% CI) 0%-14.0%]. The proportion of positive non-SNs ranged
in a prognostic logistic regression model from 9.7% (95% CI 4.0%-23.0%) for
patients with SN isolated tumor cells, tumor size of 1.1-3.0 cm, and without
vessel invasion, to 72.6% (95% CI 47.0%-89.0%) for patients with SN macro
metastasis, tumor size >3.0 cm, and with vessel invasion. CONCLUSION: We
identified three predictive factors for non-SN metastases in breast cancer
patients with a positive SN: size of the SN metastasis; primary tumor size; and
vessel invasion. We were not able to identify a specific group of patients with a
positive SN in whom the risk for non-SN metastases was less than 5%.
PMID- 17028773
TI - Health care students' differing conceptions of expertise: a challenge for inter
professional care.
AB - The aim of the study was to examine do health care students, who study at
different programs, value similar expert qualities. To investigate this issue, a
questionnaire was administered among health care students in a Finnish
polytechnic (two cohorts, total n = 466), consisting of a scale for rating the
importance of different expert qualities. The questionnaire resulted in the
following dimensions of the conceptions of expertise: (1) social skills, (2)
scientific skills, (3) innovativeness, (4) continuing self-development, and (5)
problem-solving skills. Also the Inventory of General Study Orientations (IGSO)
was applied to analyse possible motivational explanations for different
conceptions of expertise. In addition to the scales, an open-ended writing task
was used to explore in depth students' conceptions of expertise. It appeared that
study orientations were a minor factor in the study, while study environment
(study programs) clearly differentiated students' conceptions of expertise. Thus,
the study argues that health care students' conceptions of expertise are
constituted mainly on domain-specific bases and that students who graduate from
different programs may possess very diverse ideas about their profession.
Consequently, different conceptions captured during the education form a major
challenge for inter-professional care later in work-life. This phenomenon should
be taken into account when organising health care education.
PMID- 17028774
TI - Recombinant expression of human cathelicidin (hCAP18/LL-37) in Pichia pastoris.
AB - The constitutive expression of human cathelicidin LL-37 antimicrobial peptide was
achieved using the methylotrophic yeast, Pichia pastoris. An LL-37 cDNA clone was
amplified by PCR using human fetal cDNA library as template. The 111 bp fragment
encoding mature LL-37 gene was subcloned into pGAPZ-E, an episomal form of the
pGAPZB vector incorporating PARS1. It was then transformed into the P. pastoris X
33 strain for intracellular expression. A small peptide with a molecular mass of
about 5 kDa was detected by 17% peptide-PAGE analysis. The recombinant LL-37
peptide was purified from the gel and its amino acid sequence was determined by
LC-ESI-MS/MS analysis. The initiating amino acid, methionine, was still attached
to the N-terminal region of recombinant LL-37. LL-37 crude extract from P.
pastoris showed an antimicrobial activity against Micrococcus luteus as the test
strain. The successful expression of human LL-37 indicates that the system may be
applicable to the expression of other human defensins without resorting to fusion
protein constructions.
PMID- 17028775
TI - Effect of pretreatment chemicals on xylose fermentation by Pichia stipitis.
AB - Pretreatment of biomass with dilute H2SO4 results in residual acid which is
neutralized with alkalis such as Ca(OH)2, NaOH and NH4OH. The salt produced after
neutralization has an effect on the fermentation of Pichia stipitis. Synthetic
media of xylose (60 g total sugar/l) was fermented to ethanol in the presence and
absence of the salts using P. stipitis CBS 6054. CaSO4 enhanced growth and
xylitol production, but produced the lowest ethanol concentration and yield after
140 h. Na2SO4 inhibited xylitol production, slightly enhanced growth towards the
end of fermentation but had no significant effect on xylose consumption and
ethanol concentration. (NH4)2SO4 inhibited growth, had no effect on xylitol
production, and enhanced xylose consumption and ethanol production.
PMID- 17028776
TI - Cancer/testis antigen cancer-associated gene (CAGE) promotes motility of cancer
cells through activation of focal adhesion kinase (FAK).
AB - The cancer-associated gene (CAGE) is a novel cancer/testis antigen. Over
expression of it increased phosphorylation of focal adhesion kinase (FAK) and
enhanced motility of SNU387 cells. Focal adhesion, kinase-related non-kinase
(FRNK), an endogenous inhibitor of FAK, was significantly suppressed. This
suggests that CAGE-promoted motility requires FAK. The inhibition of Rho
Associated coiled-coil-containing protein kinase (ROCK), an activator of FAK,
also suppressed CAGE-promoted motility.
PMID- 17028777
TI - Metabolic characterisation of E. coli citrate synthase and phosphoenolpyruvate
carboxylase mutants in aerobic cultures.
AB - E. coli is still one of the most commonly used hosts for protein production.
However, when it is grown with excess glucose, acetate accumulation occurs.
Elevated acetate concentrations have an inhibitory effect on growth rate and
recombinant protein yield, and thus elimination of acetate formation is an
important aim towards industrial production of recombinant proteins. Here we
examine if over-expression of citrate synthase (gltA) or phosphoenolpyruvate
carboxylase (ppc) can eliminate acetate production. Knock-out as well as over
expression mutants were constructed and characterized. Knocking out ppc or gltA
decreased the maximum cell density by 14% and increased the acetate excretion by
7%, respectively decreased it by 10%. Over-expression of ppc or gltA increased
the maximum cell dry weight by 91% and 23%, respectively. No acetate excretion
was detected at these increased cell densities (35 and 23 g/l, respectively).
PMID- 17028778
TI - Pretreatment of lipase with soybean oil before immobilization to prevent loss of
activity.
AB - Lipase was pretreated with soybean oil in order to allow fatty acids to bond to
the active site before immobilization. This pretreated lipase exhibited steric
hindrance around the active site such that during immobilization, covalent bonds
were formed between the carrier and the lipase region far from the active site.
The activity of the pretreated lipase immobilized covalently on a silica gel was
530 U/g-matrix, which is 16 times higher than that of the immobilized non
pretreated lipase. In addition, the immobilized lipase activity was maintained at
levels exceeding 90% of its original activity after 10 reuses.
PMID- 17028779
TI - IgE binding to proteins from sesame and assessment of allergenicity: implications
for biotechnology?
AB - Successful prediction of the potential allergenicity of a protein may be a key
factor in the development of novel, genetically modified foods. The use of the
decision tree approach for the prediction of allergenicity is discussed. The
methods currently used for identifying allergenic proteins (including use of IgE
from patient sera for recognition of proteins) are reviewed. Finally, a specific
review of the literature concerning identification of allergens from sesame leads
to the conclusion that in the absence of validated animal models, identification
of allergenicity (and, consequently, prediction of allergenicity) may be
problematic.
PMID- 17028780
TI - Involvement of polyamines in plant response to abiotic stress.
AB - Environmental stresses are the major cause of crop loss worldwide. Polyamines are
involved in plant stress responses. However, the precise role(s) of polyamine
metabolism in these processes remain ill-defined. Transgenic approaches
demonstrate that polyamines play essential roles in stress tolerance and open up
the possibility to exploit this strategy to improve plant tolerance to multiple
environmental stresses. The use of Arabidopsis as a model plant enables us to
carry out global expression studies of the polyamine metabolic genes under
different stress conditions, as well as genome-wide expression analyses of
insertional-mutants and plants over-expressing these genes. These studies are
essential to dissect the polyamine mechanism of action in order to design new
strategies to increase plant survival in adverse environments.
PMID- 17028781
TI - Cloning and characterization of a novel small monomeric GTPase, RasL10B, with
tumor suppressor potential.
AB - Ras proteins are members of the superfamily of small GTPase. A novel human Ras
like transcript, termed RasL10B, was isolated from human blood cell cDNA library.
RasL10B gene contains four exons and three introns, which encodes a 203 amino
acid protein with a molecular mass of about 23.2 kDa. RT-PCR analysis showed that
RasL10B is expressed extensively in human tissues. Subcellular location analysis
of GFP-RasL10B fusion protein revealed that RasL10B was distributed to the
cytoplasm of COS7 cells. In addition, RasL10B was expressed in E. coli Rosette
(DE3) and purified to a homogenicity by Ni-NTA affinity chromatography. Finally,
the mRNA levels of RasL10B were down-regulated in all human breast cancer cell
lines we tested. In summary, RasL10B is a new member of Ras superfamily with
tumor suppressor potential.
PMID- 17028782
TI - Enzymatic synthesis of (R)-cyanohydrins by a novel (R)-oxynitrilase from Vicia
sativa L.
AB - The defatted seed meal of common vetch (Vicia sativa L.) served as a source of
(R)-oxynitrilase which catalyzed the enantioselective addition of HCN to
aromatic, heteroaromatic, fluoro-substituted aromatic aldehydes to produce the
corresponding enantiomeric pure cyanohydrins in yields of 52-100% and 88-99% ee
at 12 degrees C under micro-aqueous medium (diisopropyl ether) without addition
of buffer solution.
PMID- 17028783
TI - Cloning, expression, and characterization of a glycoside hydrolase family 50 beta
agarase from a marine Agarivorans isolate.
AB - The gene for a thermostable beta-agarase from Agarivorans sp. JA-1 was cloned and
sequenced. It comprised an open reading frame of 2,988 base pairs, which encode a
protein of 109,450 daltons consisting of 995 amino acid residues. A comparison of
the entire sequence showed that the enzyme has 98.8% sequence similarities to
beta-agarase from Vibrio sp. JT1070, indicating that it belongs to the family
glycoside hydrolase (GH)-50. The gene corresponding to a mature protein of 976
amino acids was inserted and expressed in Escherichia coli. The recombinant beta
agarase was purified to homogeneity. It had maximal activity at 40 degrees C and
pH 8.0 in the presence of 1 mM NaCl and 1 mM CaCl(2). The enzyme hydrolyzed
agarose as well as neoagarohexaose and neoagarotetraose to yield neoagarobiose as
the main product. Thus, the enzyme would be useful for the industrial production
of neoagarobiose.
PMID- 17028784
TI - Transgenic mice can express mutant human coagulation factor IX with higher level
of clotting activity.
AB - To improve the available values of transgenic animals, we produced a mutant human
coagulation factor IX minigene (including cDNA and intron I) with arginine at 338
changed to alanine (R338A-hFIX) by using a direct mutation technique. The R338A
hFIX minigene was then cloned into a plasmid carrying the goat beta-casein
promoter to get a mammary gland-specific expression vector. The clotting activity
in the supernatant of the transfected HC-11 cells increased to approximately
three times more than that of wild-type hFIX. Nine transgenic mice (three females
and six males) were produced, and the copy number of the foreign gene was very
different, ranging from 1 to 43 in different lines. ELISA, Western blot, and
clotting assay experiments showed that the transgenic mice could express R338A
hFIX, showing higher average levels of clotting activity than wild-type hFIX in
the milk (103.76% vs. 49.95%). The highest concentration and clotting activity of
hFIX reached 26 mug/mL and 1287% in one founder (F(0)-7), which was over 10 times
higher than that in human plasma. Furthermore, RT-PCR, APTT assay, and
histological analysis indicated that hFIX was expressed specifically in the
mammary gland without affecting the intrinsic coagulation pathway and physiologic
performance of the local tissue.
PMID- 17028785
TI - Genetic variation and population structure of oriental migratory locust, Locusta
migratoria manilensis, in China by allozyme, SSRP-PCR, and AFLP markers.
AB - Allozyme analysis, microsatellite primer PCR (SSRP-PCR), and amplified fragment
length polymorphism (AFLP) techniques were used to assess genetic diversity and
population structure of the Chinese oriental migratory locust, Locusta migratoria
manilensis. A total of 299 PCR markers (67 SSRPs and 232 AFLPs) were detected in
eight populations, of which 98.7% were polymorphic markers. The proportion of
polymorphic loci (95.5-98.8%) by SSRP+AFLP markers indicated no significant
differences between populations, and all populations exhibited a similar level of
variability; results of the allozyme analysis demonstrated that 19 loci gave rise
to a lower level of polymorphism (55.6-66.7%). The genetic distances between the
populations were relatively low. Shannon's index and Nei's gene diversity showed
low differentiation among the populations. Allozyme analysis, however, reflected
greater similarity and smaller differentiation between the populations than those
shown by SSRP and AFLP markers. Neighbor-joining dendrograms derived from both
the allozyme and SSRP+AFLP markers showed that the genetic distances among
Chinese oriental migratory locust populations were not greatly influenced by
geographic distance and breeding habitats.
PMID- 17028786
TI - Genetic diversity of the giant tiger shrimp (Penaeus monodon) in Thailand
revealed by PCR-SSCP of polymorphic EST-derived markers.
AB - A total of 90 ESTs from normal and 157 from subtractive ovarian cDNA libraries of
the giant tiger shrimp (Penaeus monodon) were sequenced. SSCP analysis of
disulfide isomerase (DSl), zinc finger protein (ZFP), PMO920, and PMT1700 was
carried out for population genetic studies of P. monodon in Thai waters. The
number of codominant alleles per locus for overall samples was 6 for PMO920, 5
for PMT1700, and 12 for ZFP, and there were 19 dominant alleles for DSI. The
observed heterozygosity of each geographic sample was 0.3043-0.5128 for PMO920,
0.3462-0.4643 for PMT1700, and 0.5000-0.8108 for ZFP. Linkage disequilibrium
analysis indicated that genotypes of these loci segregate randomly (P > 0.05).
Low genetic distance was found between pairs of geographic samples (0.0077
0.0178). The neighbor-joining tree constructed from the average genetic distance
of overall loci allocated the Andaman samples (Satun, Trang, and Phangnga) into
one cluster, and Chumphon and Trat into other clusters. Geographic
differentiation between Satun-Trat and Satun-Phangnga was found only at the ZFP
locus (P < 0.05), suggesting low degrees of genetic subdivision of Thai P.
monodon.
PMID- 17028787
TI - Mitochondrial DNA diversity and genetic differentiation of the honeybee (Apis
cerana) in Thailand.
AB - Genetic diversity of the honeybee (Apis cerana) in Thailand collected from north,
northeast, the central region, peninsular Thailand, and Samui Island (n = 181)
was examined by PCR-RFLP of ATPase6-ATPase8. Interestingly, 78 individuals
(43.09%) of the southern-latitude bees exhibited length heteroplasmy of the PCR
product. The gel-eluted ATPase6-ATPase8 (825 bp) of each bee was restricted with
TaqI, SspI, and VspI, respectively. Eight mitotypes were generated and revealed
biogeographic differentiation between conspecific samples of A. cerana. AAA, ACA,
AAD, BAA, ADA, and ABA were found only in the north-to-central samples (north,
northeast, and central region); BBB and BBC were found in the southern-latitude
bees; and BBC was restrictively found in the Samui sample. Large genetic
distances were observed between each of the north-to-central samples and
peninsular Thailand and Samui samples, but lower levels of genetic distance were
found within each region. Geographic heterogeneity and phylogenetic analyses
indicated that Thai A. cerana could be genetically differentiated into northern
Thailand, peninsular Thailand, and Samui Island populations.
PMID- 17028788
TI - A new method for the preperative and analytical electrophoresis of cells.
AB - In this paper, a new method is described for the horizontal electrophoresis of
cells on a density cushion under near-isopycnic conditions. When cell
sedimentation is minimized, the electrophoresis of red blood cells (RBC) used as
model cells within an anti-convective porous matrix (with pores over 300 microm
in diameter) was capable of separating a mixture of human and chicken RBC
according to their electrophoretic mobilities. Samples taken from the separated
RBC bands show over 90% purity for each species. The simultaneous electrophoresis
of several RBC samples carried out under identical conditions permitted the use
of comparative data based on the electrophoretic mobility of cells which differ
in their surface properties. We believe that this relatively simple system, in
which cell sedimentation and convection are minimized, has the potential to be
modified and adapted for the separation of other cell types/organelles.
PMID- 17028789
TI - Helicobacter pylori infection can modulate the susceptibility of gastric mucosa
cells to MNNG.
AB - The pathogenesis of stomach cells can be associated with their susceptibility to
exogenous dietary irritants, like nitrosamines such as dimethylnitrosamines
(DMNA), and to the effects of non-dietary factors, including Helicobacter pylori
infection. We used N-methyl-N'-nitro N-nitrosoguanidyne (MNNG) as a surrogate
agent that induces a spectrum of DNA damage similar to DMNA. Using the alkaline
comet assay, we showed that antioxidants--vitamins C and E, quercetin, and
melatonin--reduced the genotoxic effect of MNNG in H. pylori-infected and non
infected human gastric mucosa cells (GMCs). To compare the sensitivity of the
stomach and the blood, the experiment was also carried out in peripheral blood.
We observed a higher level of DNA damage induced by MNNG in H. pylori-infected
than in noninfected GMCs. We did not note any difference in the efficacy of the
repair of the damage in either type of GMC. H. pylori infection may play an
important role in the pathogenesis of GMCs, as it can modulate their
susceptibility to dietary mutagens/carcinogens, thus contributing to gastric
cancer.
PMID- 17028790
TI - Swelling of two-dimensional polymer rings by trapped particles.
AB - The mean area of a two-dimensional Gaussian ring of N monomers is known to
diverge when the ring is subject to a critical pressure differential, p c ~ N -1.
In a recent publication (Eur. Phys. J. E 19, 461 (2006)) we have shown that for
an inextensible freely jointed ring this divergence turns into a second-order
transition from a crumpled state, where the mean area scales as [A]~N-1, to a
smooth state with [A]~N(2). In the current work we extend these two models to the
case where the swelling of the ring is caused by trapped ideal-gas particles. The
Gaussian model is solved exactly, and the freely jointed one is treated using a
Flory argument, mean-field theory, and Monte Carlo simulations. For a fixed
number Q of trapped particles the criticality disappears in both models through
an unusual mechanism, arising from the absence of an area constraint. In the
Gaussian case the ring swells to such a mean area, [A]~ NQ, that the pressure
exerted by the particles is at p c for any Q. In the freely jointed model the
mean area is such that the particle pressure is always higher than p c, and [A]
consequently follows a single scaling law, [A]~N(2) f (Q/N), for any Q. By
contrast, when the particles are in contact with a reservoir of fixed chemical
potential, the criticality is retained. Thus, the two ensembles are manifestly
inequivalent in these systems.
PMID- 17028791
TI - Renormalization group analysis of polymer cyclization with non-equilibrium
initial conditions.
AB - We develop a renormalization group approach for cyclizing polymers for the case
when chain ends are initially close together (ring initial conditions). We
analyze the behavior at times much shorter than the longest polymer relaxation
time. In agreement with our previous work (Europhys. Lett. 73, 621 (2006)) we
find that the leading time dependence of the reaction rate k(t) for ring initial
conditions and equilibrium initial conditions are related, namely k (ring)(t)
proportional, variant t (-delta) and k (eq)(t) proportional, variant t (1-delta)
for times less than the longest polymer relaxation time. Here delta is an
effective exponent which approaches delta = 5/4 for very long Rouse chains. Our
present analysis also suggests a "sub-leading" term proportional to (ln t)/t
which should be particularly significant for smaller values of the renormalized
reaction rate and early times. For Zimm dynamics, our RG analysis indicates that
the leading time dependence for the reaction rate is k(t) approximately 1/t for
very long chains. The leading term is again consistent with the expected relation
between ring and equilibrium initial conditions. We also find a logarithmic
correction term which we "exponentiate" to a logarithmic form with a Landau pole.
The presence of the logarithm is particularly important for smaller chains and,
in the Zimm case, large values of the reaction rate.
PMID- 17028793
TI - Is three selected parameters adequate to monitor rheumatoid arthritis?
AB - This pilot study was done to choose which among the five core set criteria will
have more discriminating ability and which is easy to administer in a clinical
setting. Forty-eight patients recently diagnosed to have rheumatoid arthritis
(RA) were recruited for the study. They were assessed by a rheumatologist in each
visit (initial and after 2 months of treatment), for five core measures: patient
assessment, pain (measured on VAS scale), number of tender joints, health
assessment questionnaire (HAQ) score, and erythrocyte sedimentation rate (ESR).
All patients were treated with methotrexate 7.5 mg per week and hydroxychloroquin
400 mg per day with adequate dose of NSAIDs. Patients with associated conditions
like stroke, ischemic heart disease, and other physical comorbidity were
excluded. They were categorized as 20, 50, and 70% improvement, if four of the
five criteria occur. The Wilcoxon signed rank test and discriminant function
analysis were done to identify the order of importance of measures on influencing
the outcome. The ESR followed by patient improvement scale showed the least
changes, while HAQ showed the highest changes. Discriminate function analysis has
been carried out to see which factors influenced in grouping them for responses
with post hoc analyses of finding the order of importance of these factors in
classifying the response. Pain scale, ESR, HAQ score, patient improvement scale,
and tender score were in the decreasing value of importance. The pain scale, HAQ,
and ESR, which are more objective and discriminate measures, are useful as
measures in RA.
PMID- 17028792
TI - Severity of vertebral fracture reflects deterioration of bone microarchitecture.
AB - INTRODUCTION: Bone microarchitecture, a component of bone strength, is generally
measured on transiliac bone biopsy samples. The objective of this study was to
determine whether assessment of four grades of vertebral fracture severity could
serve as a noninvasive surrogate marker for trabecular bone volume and
microarchitecture. METHODS: Baseline vertebral fracture severity was determined
by semiquantitative assessment of spine radiographs from 190 postmenopausal women
with osteoporosis. Bone-structure indices were obtained by 2D histomorphometry
and 3D microcomputed tomography (CT) analyses. Significance of differences was
determined after adjusting for age, height, and lumbar spine bone mineral
density. RESULTS: There were significant (P < 0.05) trends in decreasing bone
volume, trabecular number, and connectivity, and increasing trabecular separation
with greater vertebral fracture severity. Histomorphometric bone volume was 25
and 36% lower (P < 0.05) in women with moderate and severe fractures than in
women with no fractures, respectively. Compared with women without fractures,
women with mild, moderate, and severe fractures had lower (P < 0.05) microCT bone
volume (23, 30, and 51%, respectively). CONCLUSIONS: Microarchitectural
deterioration was progressively worse in women with increasing severity of
vertebral fractures. We conclude that assessment of vertebral fracture severity
is an important clinical tool to evaluate the severity of postmenopausal
osteoporosis.
PMID- 17028794
TI - Modification of collagen formation using supplemented mesh materials.
AB - BACKGROUND: Formation of recurrent inguinal and incisional hernia shows an
underlying defect in the wound healing process. Even following mesh repair an
altered collagen formation and insufficient mesh integration has been found as
main reason for recurrences. Therefore the development of bioactive mesh
materials to achieve a local modification of the scar formation to improve
patients outcome is advisable. METHODS: Thirty-six male Wistar rats were used
within this study. A Mersilene (R) mesh sample was implanted after midline skin
incision and subcutaneous preparation. Before implantation mesh samples were
incubated for 30 minutes with either one of the following agents: doxycycline,
TGF-beta 3, zinc-hydrogeneaspartate, ascorbic acid, hyaluronic acid. Incubation
with a physiologic 0.9 % NaCl solution served as control. Seven and 90 days after
mesh implantation 3 animals from each group (n = 6) were sacrificed for
morphological observations. Collagen quantity and quality was analyzed measuring
the collagen/protein as well as the collagen type I/III ratio. RESULTS: Following
an implantation interval of 90 days supplementation with doxycycline (39.3 +/-
7.0 microg/mg) and hyaluronic acid (34.4 +/- 5.8 microg/mg) were found to have a
significantly increased collagen/protein ratio compared to implantation of the
pure Mersilene (R) mesh samples (28.3 +/- 1.9 microg/mg). Furthermore, an overall
increase of the collagen type I/III ratio was found in all groups indicating scar
maturation over time. However, no significant differences were found after 7 and
90 days of implantation comparing collagen type I/III ratio of supplemented mesh
samples and control group. CONCLUSIONS: In summary, we found an influence of
supplemented mesh materials on collagen deposition. However, the investigated
bioactive agents with reported influence on wound healing were not associated
with an improved quality in scar formation.
PMID- 17028795
TI - Karyotypic analysis of Skimmia japonica (Rutaceae) and related species.
AB - A karyotypic analysis of three species of Skimmia (Rutaceae) in East Asia was
performed that examined 88 individuals from 53 localities. Chromosome numbers of
S. japonica, S. reevesiana and S. arisanensis were 2n=30, 31, 32 (=30+0-2B),
2n=60 and 2n=60, respectively. The chromosome number of S. arisanensis was
reported for the first time. All species had a large chromosome pair or quartet
(the first pair or quartet) with a median-submedian centromere in the karyotype.
In S. japonica the arm ratio of this first pair was considerably variable and
showed a geographical pattern. In the northern half of the distribution range,
Sakhalin, Hokkaido, Honshu, Shikoku and part of Kyushu, the arm ratio was 1-1.2,
while in the southern half, part of Kyushu, Ryukyu and Taiwan, the arm ratio was
very variable and ranged from 1.2 to 2.4. In S. japonica the first pair was
sometimes rather heteromorphic; however, the heteromorphism was not related to
sex of the plant.
PMID- 17028797
TI - Osteoclastic bone resorption through receptor tyrosine kinase and extracellular
signal-regulated kinase signaling in mature osteoclasts.
AB - It has recently been suggested that signaling through receptor tyrosine kinases
(RTKs) expressed on mature osteoclasts is involved in osteoclastic bone
resorption. This study investigated the role and mechanism of two major RTKs
expressed on mature osteoclasts, fibroblast growth factor receptor type 1 (FGFR1)
and Tyro 3. Among the FGF receptors (FGFR1-4), only FGFR1 was detected on
isolated mouse osteoclasts, while all FGFRs were identified on mouse osteoblasts.
Tyro 3 was seen only in mature osteoclasts among bone cells. FGF-2 moderately
stimulated pit formation by isolated rabbit osteoclasts at low concentrations
(>==10(-12) M), whereas at high concentrations (>==10(-9) M) it strongly
stimulated pit formation by unfractionated bone cells. Gas6, the ligand of Tyro
3, was expressed ubiquitously in bone cells and stimulated osteoclast function to
form resorbed pits on a dentine slice. Both FGF-2 and Gas6 upregulated the
phosphorylation of cellular proteins, including extracellular signal-regulated
kinase (ERK), and increased the kinase activity of immunoprecipitated FGFR1 and
Tyro 3, respectively, in mouse osteoclasts. The stimulation of these cytokines on
mouse and rabbit osteoclast functions was abrogated by PD98059, a specific
inhibitor of ERK. These results strongly suggest that these cytokines act
directly on mature osteoclasts through the activation of RTKs and ERK, causing
the stimulation of bone resorption.
PMID- 17028796
TI - Functional consequences of stenophylly for leaf productivity: comparison of the
anatomy and physiology of a rheophyte, Farfugium japonicum var. luchuence, and a
related non-rheophyte, F. japonicum (Asteraceae).
AB - We investigated the anatomical and physiological characteristics of stenophyllous
leaves of a rheophyte, Farfugium japonicum var. luchuence, and sun and shade
leaves of a non-rheophyte, F. japonicum, comparing three different populations
from coastal, forest floor, and riparian habitats. Light adaptation resulted in
smaller leaves, and riparian adaptation resulted in narrower leaves
(stenophylly). The light-saturated rate of photosynthesis (P (max)) per unit leaf
area corresponded to the light availability of the habitat. Irrespective of leaf
size, the P (max) per unit leaf mass was similar for sun and shade leaves.
However, the P (max) per mass of stenophyllous leaves was significantly lower
than that of sun and shade leaves. This was because the number and size of
mesophyll cells were greater than that required for intercellular CO(2)
diffusion, which resulted in a larger leaf mass per unit leaf area. Higher cell
density increases contact between mesophyll cells and enhances leaf toughness.
Stenophyllous leaves of the rheophyte are frequently exposed to a strong water
flow when the water level rises, suggesting a mechanical constraint caused by
physical stress.
PMID- 17028798
TI - Implications of transcriptional coactivator CREB binding protein complexes in
rheumatoid arthritis.
AB - Transcriptional coactivators have crucial roles in eukaryotic transcription. It
has been suggested that one of the coactivators, cAMP response element binding
protein (CREB) binding protein (CBP), regulates gene expression with a number of
transcription factors via two mechanisms. One is the recruitment of general
transcriptional machinery to the promoters. The other is its intrinsic and
associated histone acetyltransferase (HAT) activity, which increases the
accessibility of the activator to DNA, and the acetylation of nonhistone
proteins. Rheumatoid arthritis (RA) is characterized by the inflammation and
proliferation of synovium, leading to the destruction of articular cartilage and
bone. To understand the pathogenesis of RA, we focused the transcription
mechanism through CBP in synoviocytes and chondrocytes. We identified Notch-1 in
synoviocytes and p34(SEI-1) in chondrocytes as CBP binding proteins by yeast two
hybrid screening. It was also suggested that the acetylation of p53 could repress
transactivation in RA synoviocytes. These associations may regulate proliferation
and apoptosis. This study suggests that regulation of the coactivator could
become a novel strategy for RA therapy.
PMID- 17028799
TI - Inflammatory cytokines and systemic-onset juvenile idiopathic arthritis.
AB - Systemic-onset juvenile idiopathic arthritis (JIA) is a severe and steroid
dependent disease, which sometimes progresses to the fatal disease macrophage
activation syndrome. An investigation of inflammatory cytokine levels revealed
increases in IL-6 in serum of systemic-onset disease patients. Continuously
elevated levels of IL-6 in serum may play a important role in manifesting the
clinical symptoms and signs of systemic-onset JIA, including spiking fever, rash,
arthritis, and serositis. The characteristic fever spikes parallel IL-6 levels.
Long-term exposure to high levels of IL-6 in children results in severe growth
impairment, which was strongly suggested by the recent establishment of IL-6
transgenic mice. To avoid disease progression to macrophage activation syndrome
and the adverse effects of high-dose corticosteroids, it might be reasonable to
inhibit the formation of IL-6/IL-6R complex in order to block the binding to
gp130 receptor, a biologically active receptor for IL-6. This review will provide
evidence of the relationship between IL-6 homeostasis and systemic-onset JIA, and
our recent trials of anti-IL-6R antibody (MRA) for children with acute systemic
disease intractable to long-term and high-dose corticosteroid therapy. MRA could
be a therapeutic modality for children with systemic-onset JIA intractable to
high-dose corticosteroids.
PMID- 17028800
TI - Recombinant adeno-associated virus preferentially transduces human, compared to
mouse, synovium: implications for arthritis therapy.
AB - Despite a number of published reports, including from our own laboratory,
suggesting that adeno-associated virus (AAV) transduces mouse synovium, a careful
analysis demonstrated transduction predominantly of the subsynovial muscle
tissue, while the synovial lining is poorly transduced. To investigate the
potential of AAV to transduce human synovium, three human rheumatoid arthritis
(RA) and two murine collagen-induced arthritis (CIA) synovial cell lines were
infected with recombinant AAV (rAAV) vectors encoding either mouse IL-10 or IL-4.
Low-level transgene expression was observed. However, either Gamma-irradiation or
the addition of a low-titer E1-, E3-deleted recombinant adenovirus resulted in up
to a 100-fold increase in transgene product in the human, but not the mouse, cell
lines. RA synovial tissues implanted subcutaneously in severe combined
immunodeficiency (SCID) mice, which were subsequently infected with rAAV, showed
marked increases in transgene expression when co-infected with adenovirus. To our
knowledge, this is the first study to show that intact human synovial tissues can
be transduced by rAAV, and it suggests that murine arthritis may not be an
optimal model to study rAAV as a gene transfer vector. Further studies to
elucidate the mechanisms limiting gene transduction in human synovium may allow
optimization of this vector for the treatment of arthritis.
PMID- 17028801
TI - Effect of ebselen, a scavenger of reactive oxygen species, on chondrocyte
metabolism.
AB - Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a synthetic heterocyclic
seleno-organic compound, has been shown to act as a scavenger of reactive oxygen
species (ROS). We have previously reported that interleukin-1 (IL-1) inhibited
proteoglycan (PG) synthesis and induced the production of ROS in cartilage
explants and isolated chondrocyte cultures. In this study, we report the
protective effect of ebselen against IL-1-mediated inhibition of PG synthesis and
ROS induction in cultured cartilage explants and chondrocytes. Ebselen also
reversed the inhibition of PG synthesis in mechanically stressed cultured
chondrocytes. These data suggest that the use of the antioxidant ebselen may be a
useful tool for studying the mechanisms of cartilage degradation.
PMID- 17028802
TI - Radiological follow-up study of rheumatoid wrists after radio-lunate limited
arthrodesis with ulnar head resection.
AB - Radio-lunate limited arthrodesis (RLA) is an established surgical intervention
for damaged rheumatoid arthritis (RA) wrists. The goal of RLA is to conserve the
range of motion (ROM) and level of activities of daily life (ADL) by delaying
more extensive fusion. In this study, we retrospectively reviewed the outcome of
RLA with ulnar head resection (UHR) in terms of pain score, ROM, and radiographic
parameters, including carpal height ratio, ulnar translation ratio, and palmar
subluxation. The clinical factors, such as dose of corticosteroids per day and
laboratory examination data before surgery, including C-reactive protein (CRP),
erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF), did not
influence the results of the surgery. The changes in these clinical factors were
also statistically analyzed in relation to the Schulthess classification of
preoperative radiographs of wrists reported by Simmen and Huber: Type I
(ankylosis type), Type II (osteoarthritis type), and Type III (disintegration
type). This study hypothesized that RLA with UHR would provide no significant
improvement in Type III wrists. The results showed that RLA with UHR resulted in
stable wrists with excellent pain relief and with limited, but temporary,
functional ROM, suggesting that this procedure seems to be applicable for all
types of wrists within this group of patients.
PMID- 17028803
TI - HLA-DRB1 haplotype did not affect the medium-term results of total knee
arthroplasty in patients with rheumatoid arthritis.
AB - This study investigated whether the HLA-DRB1 "susceptible allele" (SA) genotype
is predictive for total knee arthroplasty (TKA) failure in patients with
rheumatoid arthritis (RA). The results of 49 TKAs (30 RA patients) with an
average follow-up of 7.9 years (range 5-15 years) were analyzed using a 12-item
questionnaire and the Knee Society system. HLA-DRB1 alleles were used to estimate
the severity of RA and divide the patients into three categories depending upon
the gene dose of SA (SA+/+, SA+/-, and SA-/-). For all three categories, the 12
item questionnaire had significantly improved postoperatively, but without
significant difference. We divided the 12 items of the questionnaire into two
groups: knee-relevant parameters and general parameters. Patients in all three
groups improved similarly in knee-relevant parameters. In contrast, those
homozygous for SA (SA+/+) benefited less in general parameters. The average
radiolucency score was 1.87 mm, with no difference being detected among the three
groups. The HLA-DRB1 genotype did not affect the survival of the knee implants.
Overall, patients without the RA-associated HLA gene benefited most from TKA as
they improved not only in knee function, but also in parameters of general
functional status.
PMID- 17028804
TI - Efficacy of plasma exchange therapy for Kawasaki disease intractable to
intravenous gamma-globulin.
AB - Kawasaki disease (KD) causes coronary artery lesions (CALs) in 500 Japanese
children each year. Intravenous gamma-globulin (IVGG) decreases the incidence of
these lesions from 25% to 8% of the total KD cases. We examined whether plasma
exchange is a safe and effective prophylaxis against CALs in children with KD
intractable to IVGG therapy. Eighty-nine children with KD at high risk of CALs
were selected on the basis of increases in fractional changes in inflammatory
markers such as white blood cell count, neutrophil count, and C-reactive protein
between the baseline and 1-2 days after IVGG treatment. Of 105 children who
received a second course of IVGG therapy because the initial course was
ineffective, plasma exchange (PE) was performed in 46 children who had not
responded to the second IVGG treatment. The outcome was compared with the results
when a third course of IVGG therapy was given to the other 59 children. No
complications occurred with the plasma exchange therapy. CALs developed in only 8
of the 46 children (17.3%) who underwent plasma exchange, but they occurred in 24
of the 59 (40.7%) who had received a third course of IVGG therapy (P << 0.0012).
We concluded that PE was a safe, effective prophylactic measure against CALs in
children with KD intractable to IVGG therapy. PE should be performed at an early
stage, as soon as fractional increases in inflammatory markers are found after
IVGG therapy.
PMID- 17028805
TI - Total ankle arthroplasty for deformity of the foot in patients with rheumatoid
arthritis using the TNK ankle system: clinical results of 21 cases.
AB - We report the results of total ankle arthroplasty (TAA) of 21 ankle joints
performed on 19 patients with rheumatoid arthritis (RA) using the Japanese TNK
ankle system. The clinical evaluation for an average follow-up period of 33.8
months was based on the ankle analysis system. The total score, pain score, range
of motion, and walking ability significantly improved postoperatively compared
with the preoperative period. These parameters also showed significantly
different values between the preoperative and the follow-up periods. However, the
range of motion significantly improved postoperatively. In the evaluation of TAA
using the TNK ankle system, a radiolucent line of about 1 mm was detected, but
there was no dislocation or sinking of the tibial and talar prostheses. There
were no severe complications except for two cases with a delayed wound healing
and one with a deep infection. These results suggest that if the talocrural joint
only was destroyed and the neighboring joints (subtalar or talonavicular) had
fibrous fusion, or the patient had relatively fewer activities in daily life or
was an elderly person, TAA using the TNK ankle system was effective for the
treatment of painful and disabling ankle joints in patients with RA in the middle
of the follow-up period.
PMID- 17028806
TI - Requirement of mitogen-activated protein kinase for collagenase production by the
fibronectin fragment in human articular chondrocytes in culture.
AB - Fibronectin fragments have been shown to up-regulate matrix metalloproteinase
production in chondrocytes. We investigated the roles of mitogen-activated
protein kinase (MAPK) pathways activated by the COOH-terminal heparin-binding
fibronectin fragment (HBFN-f) in collagenase production by human chondrocytes in
culture. In articular cartilage explant culture, HBFN-f stimulated type II
collagen cleavage by collagenase in association with increased secretion of MMP-1
and MMP-13. In human articular chondrocytes, HBFN-f induced the collagenases with
activation of the extracellular signal-regulated kinase (ERK), p38, and the c-Jun
NH(2)-terminal kinase (JNK). PD98059 that inhibits the ERK pathway blocked HBFN-f
stimulated production of MMP-1 and MMP-13 in explant culture. SB203580 at 1
microM, the concentration that inhibits p38 only, partially suppressed HBFN-f
induced collagenase production, whereas at 10 microM, the inhibitor that blocks
both p38 and JNK almost completely inhibited collagenase induction. PD98059 and
SB203580 individually blocked HBFN-f-increased cleavage of type II collagen in
the explant culture, although 10 microM SB203580 strongly inhibited the collagen
cleavage compared with 1 microM of the inhibitor. These results indicate that
collagenase production leading to type II collagen cleavage in cartilage explants
requires ERK, p38, and JNK.
PMID- 17028807
TI - A case of lupus cystitis with a history of idiopathic thrombocytopenic purpura.
AB - A 36-year-old Japanese woman who had been diagnosed as having systemic lupus
erythematosus (SLE) at the age of 34 began to complain of severe bowel symptoms
and developed severe hydroureteronephrosis. She had a history of idiopathic
thrombocytopenic purpura. Biopsy specimens from her bladder showed interstitial
cystitis. She was diagnosed as having lupus cystitis, and treated with
intravenous methylprednisolone pulse therapy followed by oral prednisolone and
ureter catheterization. Her urinary and bowel symptoms were alleviated and the
level of hydroureteronephrosis improved. We note that cystitis could be a primary
manifestation of SLE. Patients not only with SLE but also with some autoimmune
diseases require careful urological evaluation when they complain of severe bowel
symptoms.
PMID- 17028808
TI - Munchausen syndrome with foreign-body granuloma mimicking rheumatic diseases.
AB - A 37-year-old man was admitted to our hospital because of fever, polyarthralgia,
and subcutaneous tumors. There was swelling of the bilateral wrists and ankles,
and subcutaneous tumors over the bilateral elbow joints. Despite his complaints
of multiple symptoms, clinical investigations failed to reveal any abnormality.
Although laboratory parameters improved rapidly after steroid therapy, the
symptoms remained unchanged, and there was an enormous discrepancy between the
laboratory data and his symptoms. A biopsy specimen from one of the subcutaneous
tumors revealed foreign-body granuloma associated with a foreign body fragment.
Because the nursing staff later discovered that the patient had been carrying out
self-injection, a diagnosis of Munchausen syndrome was made. Munchausen syndrome
should be included in the differential diagnosis of rheumatic diseases.
PMID- 17028810
TI - A case of Weber-Christian disease associated with myelodysplastic syndrome.
AB - We report the case of a 73-year-old man with myelodysplastic syndrome (MDS) who
developed Weber-Christian disease (WCD). Bone marrow aspirates showed refractory
anemia with abnormal karyotypes such as trisomy 8, trisomy 8 and 14, and trisomy
8, 9, and 14. The patient had intermittent fever associated with multiple tender
erythematous nodules on the skin. A biopsy sample taken from a nodule revealed
focal subcutaneous infiltration of neutrophils and necrotizing fat tissue. We
diagnosed the patient as having lobular panniculitis associated with
myelodysplastic syndrome. The serum levels of soluble interleukin-2 (IL-2)
receptor, interferon-Gamma, IL-1-Beta, IL-6 and tumor necrosis factor-Alpha were
elevated in the active state but returned to normal after prednisolone therapy.
This finding appears to implicate a T-cell immune response in the pathogenesis of
Weber-Christian disease.
PMID- 17028809
TI - Abacterial prostatitis and primary biliary cirrhosis with SjOgren's syndrome.
AB - In patients with SjOgren's syndrome (SS), the salivary and lacrimal glands are
often affected, although other epithelial tissues can become inflamed. Here, we
report the first case of abacterial prostatitis in a patient with SS complicated
by primary biliary cirrhosis. Histologically, the distribution and subpopulation
of infiltrating lymphocytes were similar in the salivary gland, liver, and
prostate. Treatment with steroid was successful. We speculate that the prostate
may be one of the target organs in SS.
PMID- 17028811
TI - Hemagglutination of preoperative blood donation in patients with rheumatoid
arthritis.
AB - We gave preoperative blood transfusions to 37 patients with rheumatoid arthritis
(RA) and 35 patients with osteoarthritis (OA), including some whose baseline
hemoglobin level was less than 10 g/dl. Transfusion packs can preserve whole
blood containing citrate phosphate dextrose (CPD) for 3 weeks. The baseline
hemoglobin level of RA cases was 10.4 g/dl (range 8.4-13.1 g/dl), and that of OA
cases was 11.9 g/dl (range 10.4-15.0 g/dl). By collecting 200-400 g every week
before the operation, the total was 800-1200 g. Erythropoietin was given to
patients intramuscularly when their hemoglobin was less than 13 g/dl after blood
had been collected. Hemagglutination, with diameters of more than 1 cm, made
filter occlusions in 11 RA cases (30%) and one OA case (3%) (P << 0.0031) after
retransfusion. There were no differences between hemagglutination patients
(agglutination group) and nonhemagglutination patients (nonagglutination group)
regarding baseline C-reactive protein (CRP), white blood cells, platelets, or
fibrinogen. We could not predict the formation of macrohemagglutination in the
packs collected during the clinical course. In RA cases, allogenic transfusions
were performed for four cases (36%) in the agglutination group and for one case
(12%) in the nonagglutination group. Preoperative transfusion for the RA patients
showed hemagglutination in some cases, and highlighted the need for modifications
to reduce these hemagglutinations.
PMID- 17028812
TI - Reiter's syndrome following intravesical bacille biliE de Calmette-GuErin
treatment for superficial bladder carcinoma: report of six cases.
AB - We report the cases of six patients who developed acute Reiter's syndrome
following intravesical bacille biliE de Calmette-GuErin (BCG) immunotherapy for
superficial bladder cancer. After the third to eighth BCG intravesical injection,
the patients developed conjunctivitis, aseptic urethritis, and polyarthritis
consistent with a diagnosis of Reiter's syndrome. HLA-B27 antigen was negative in
five of the patients examined. Two of the patients responded to nonsteroidal anti
inflammatory drugs for polyarthritis, and the other four responded to steroids
(prednisolone 5-10 mg/day). The frequent use of intracavitary BCG may increase
the incidence of BCG-induced Reiter's syndrome. Further analysis of the
relationship between HLA-B and -DR alleles and arthritis should shed light on the
mechanism of BCG-induced Reiter's syndrome.
PMID- 17028813
TI - Gait analysis in an osteoarthritis patient with restoration of the hip joint
space following contralateral total hip arthroplasty: a case report.
AB - We present the case of a patient who, after undergoing unilateral total hip
arthroplasty (THA), achieved pain reduction in the contralateral hip accompanied
by restoration of the radiographic joint space. We conducted gait analysis to
clarify the dynamic factors affecting the natural course of osteoarthritis (OA).
Our findings revealed that the patient walked with exaggerated adduction of the
hip following the contralateral THA, causing substantial regeneration of joint
loading.
PMID- 17028814
TI - Revised list of acronyms.
PMID- 17028815
TI - Proposed [corrected] Japanese guidelines for the use of infliximab for rheumatoid
arthritis.
AB - Differences in ethnic backgrounds as well as in medical and socioeconomic status
often affect both the efficacy and adverse effects of medications. Recent data
suggest an increased risk of opportunistic infections, especially tuberculosis
(TB), among rheumatoid arthritis (RA) patients receiving infliximab, a chimeric
monoclonal anti-tumor necrosis factor alpha (TNF-alpha) antibody. In this regard,
the annual incidence of TB is approximately five times higher in Japan than in
the United States. Furthermore, since Bacillus Calmette-Guerin vaccination is
mandatory in childhood when the skin test for purified protein derivative (PPD)
is negative, a high incidence of false-positive PPD skin tests is observed among
the Japanese population. In addition, the upper limit of methotrexate dosage to
be used for RA is lower in Japan. We have therefore established official
guidelines for the proper use of infliximab in Japanese RA patients. In this
review, an algorithm for the diagnosis and management of TB in RA is presented in
an evidenced-based form.
PMID- 17028816
TI - The low-throughput protein A adsorber: an immune modulatory device. Hypothesis
for the mechanism of action in the treatment of rheumatoid arthritis.
AB - To achieve specific removal of pathogenic antibodies (Ab) or immune complexes
(IC), several adsorbers have been developed. We discuss the mode of action of low
throughput staphylococcal protein A (SPA) immunoadsorption. The SPA-based
Prosorba apheresis is likely to modify some of the autoantibodies (autoAb) or IC.
The low-throughput adsorber showed very limited adsorption capacity of
circulating autoAb and/or circulating IC. Besides changes of humoral diagnostic
parameters, cellular changes could be observed in the Prosorba-treated patients.
These changes were rather similar to those that have been observed in a patient
successfully treated with Ab against tumor necrosis factor alpha. We propose an
adsorber-catalyzed conversion of small, tissue-penetrating, scarcely detectable,
non-complement-binding, proinflammatory IgG-rheumatoid factor (RF)-based IC into
the more readily phagocytosed species of IC: intermediate-sized, partially
cryoprecipitable, non-tissue penetrating IC that are opsonized with complement.
These IC are rather short-lived and could quickly be cleared by the body's
scavenging system.
PMID- 17028817
TI - Intracellular signal transduction pathways: good therapeutic targets for joint
destruction in rheumatoid arthritis.
AB - Preventing joint destruction is one of the most challenging issues in treating
patients with rheumatoid arthritis (RA), and I propose that intracellular
signaling pathways in osteoclasts and synovial fibroblastic cells (SFCs) can be
good therapeutic targets. Osteoclasts are primarily involved in the bone
destruction in RA joints, and SFCs support osteoclast differentiation and
activation by producing various proinflammatory cytokines including receptor
activator of NF-kappaB ligand (RANKL), the osteoclast differentiation factor
belonging to the tumor necrosis factor-alpha superfamily. Suppressing c-Src
pathways by adenovirus vector-mediated C-terminal Src family kinase (Csk) gene or
Ras/extracellular-regulating kinase (ERK) pathways by introducing dominant
negative Ras (Ras(DN)) adenovirus reduced osteoclastic bone resorption as well as
the abnormal proliferation and interleukin-6 production of SFCs, and the local
injection of these viruses ameliorated the joint destruction in adjuvant
arthritis rats. Moreover, chondrogenic differentiation of SFCs could be induced
by stimulating activin receptor-like kinase 3 pathways.
PMID- 17028818
TI - Overcoming treatment unresponsiveness mediated by P-glycoprotein overexpression
on lymphocytes in refractory active systemic lupus erythematosus.
AB - P-glycoprotein (P-gp) expels various drugs from cells, resulting in multidrug
resistance, including against glucocorticoids. Here, we present a case of
systemic lupus erythematosus (SLE) that suggests the importance of initial
intensive treatment in overcoming unresponsiveness due to P-gp overexpression on
activated lymphocytes. A 28-year-old woman had been diagnosed with highly active
SLE including severe pericarditis, hemolytic anemia, lupus nephritis, and
retinopathy. The disease activity of SLE progressed despite 1 mg/kg per day oral
prednisolone. At the time, P-gp expression was extremely high, as evaluated by
flow cytometric analysis on peripheral lymphocytes. After intensive treatment
with three courses of methylprednisolone pulse therapy and plasmapheresis, we
succeeded in controlling disease activity in association with marked reduction of
P-gp overexpression; namely, the clinical symptoms immediately improved along
with the reduction of P-gp expression. These results imply that patients with
highly active SLE might have drug unresponsiveness that is mediated by P-gp
overexpression on lymphocytes. Therefore, downregulation of P-gp by initial
intensive immunosuppressive therapy might be important for overcoming
glucocorticoid resistance. We also propose that measurement of P-gp on
lymphocytes is a useful test for prediction of drug resistance and may assist in
the selection of appropriate initial treatment.
PMID- 17028819
TI - Doppler sonographic analysis of synovial vascularization in knee joints of
patients with rheumatoid arthritis: increased color flow signals and reduced
vascular resistance.
AB - Synovial vascularization was analyzed by power Doppler and spectral Doppler
sonography in 42 knee joints of 28 patients with rheumatoid arthritis. The
synovial vessels with greater intensity of color flow signals demonstrated
significantly lower indicators of vascular resistance - resistive index (P <
0.01) and pulsatility index (P < 0.01) - than those with lesser intensity.
Consequently, an inverse correlation was observed between intensity of color flow
signals and both resistive index (P < 0.01) and pulsatility index (P < 0.01).
PMID- 17028820
TI - Doppler sonographic evaluation of effect of treatment with infliximab (Remicade)
for rheumatoid arthritis.
AB - Synovial vascularization in the knee joints of six patients with rheumatoid
arthritis who were treated with infliximab was evaluated by Doppler sonography.
Power Doppler sonography demonstrated a significant reduction of color flow
signals (P < 0.05), and spectral Doppler sonography demonstrated a significant
increase in vascular resistance (P < 0.05) at week 6 (after three injections)
evaluation of the therapy. A significant decrease in the number of tender joints
(P < 0.05) and C-reactive protein value (P < 0.05) was also observed in these
patients.
PMID- 17028821
TI - Musculoskeletal pain in Japan: prevalence and interference with daily activities.
AB - We estimated the prevalence of musculoskeletal pain in five anatomical areas and
their interference with daily activities (IDA) in a Japanese adult population (n
= 3188). A questionnaire survey was conducted among participants in health
examinations at three health care centers. On a drawing with predefined body
regions, participants marked the regions affected by pain and the regions
affected by IDA due to the pain, respectively. Overall prevalence of
musculoskeletal pain was 41.4% (M 40.9%, F 42.2%) with a significant increase
with age. Neck and shoulder area showed the highest prevalence of pain (20.3%; M
19.6%; F 21.3%), followed by lower back area (19.1%; M 20.1%; F 17.5%), hip and
knee area (11.1%; M 9.1%; F 14.3%), elbow, wrist, and hand area (7.4%; M 6.6%; F
8.6%), and ankle and foot area (5.8%; M 5.5%; F 6.3%). Overall percentage of IDA
in musculoskeletal pain was 20.5%. After adjustment for age and sex, the ranking
of percentage of IDA in the pain was: (1) neck and shoulder area (31.0%), (2)
elbow, wrist, and hand area (21.5%), (3) ankle and foot area (18.8%), (4) lower
back area (17.9%), and (5) hip and knee area (17.4%). Overall percentage of
treatment for musculoskeletal disorders was 6.6% (M 4.7%, F 9.7%), which remained
28.1% (M 21.6%, F 38.0%) even in those who described IDA due to pain. According
to our estimates, 42.2 million (41.2%) of Japanese adults might suffer from
musculoskeletal pain and 9.1 million (8.8%) might encounter IDA due to the pain.
Because of high prevalence and IDA, musculoskeletal pain is one of the health
problems to be given high priority in Japan.
PMID- 17028822
TI - Burden of musculoskeletal pain in Japan.
AB - Based on the prevalence of musculoskeletal pain in the context of interference
with daily activities (IDA) and treatment for musculoskeletal disorders in the
study population (n = 3188), we estimated the prevalence and years lived with
disability (YLD) of musculoskeletal pain in Japan. The total of 42,287 thousand
(41.2%) of Japanese adult people was estimated to suffer from musculoskeletal
pain. Among them, 9127 thousand was estimated to interfere with daily activities
due to the pain. Overall YLD for musculoskeletal pain in Japan were estimated at
1,297,843.7 (1263.6 per 100,000). The YLD for Pain without IDA were 33,159.3
(32.3 per 100,000) and the YLD for Pain with IDA were 1,264,684.4 (1231.3 per
100,000). One-way sensitivity analysis showed that the YLD of musculoskeletal
pain might increase to 4,421,844.0 (4305.2 per 100,000) with the increased
disability weight for Pain without IDA of 0.1, while they might inversely
decrease to 1,018,875.0 (992.0 per 100,000) with the increased treatment rate in
Pain with IDA of 100%. Musculoskeletal pain imposes a substantial burden on the
Japanese adult population. To allow the population to keep their health-related
quality of life, health professionals should pay more attention to
musculoskeletal pain and make positive efforts to improve prevention and control
of musculoskeletal pain.
PMID- 17028823
TI - Observation of retrieved ceramic-on-ceramic articular surface: a case of revised
total hip arthroplasty due to failure of the support ring.
AB - We report the case of a 63-year-old woman who required revision surgery for
ceramic-on-ceramic total hip arthroplasty (THA) due to failure of the support
ring. We retrieved the ceramic cup and head, observed it macroscopically and
measured it to determine its shape condition (sphere diameter, sphericity, and
circularity) and surface condition (surface roughness by scanning electronic
microscopy). Although abrasion was not found at the sliding surface of either the
cup or head, it was observed at the edges of the cup and at one part of the head.
We point out the risk of the edge contact and conclude the possibility of micro
motion between the cup and the head during walking or loading in vivo, and that
contact had taken place at such parts.
PMID- 17028824
TI - HLA-B52-positive vasculo-Behcet disease: usefulness of magnetic resonance
angiography, ultrasound study, and computed tomographic angiography for the early
evaluation of multiarterial lesions.
AB - We report a case of HLA-B52-positive Behcet disease accompanied by multiarterial
lesions. A 24-year-old woman was suffering from sporadic high fever and recurrent
oral and genital ulcers, and laboratory data revealed severe inflammation. A
diagnosis of Behcet disease was made. Magnetic resonance angiography, ultrasound
study, and computed tomographic angiography demonstrated multiarterial lesions
that had caused no symptoms. These noninvasive examinations were extremely useful
in evaluating asymptomatic early vascular lesions.
PMID- 17028825
TI - Rapidly aggravated Mycobacterium avium infection in a patient with rheumatoid
arthritis treated with infliximab.
AB - Infliximab was introduced along with methotrexate 8 mg/week to a female patient
with intractable rheumatoid arthritis. Although a dramatic improvement of her
arthritic symptoms was achieved immediately, a small nodular shadow developed in
the right middle field of her lung, visible on chest X-ray at the third
injection. Because the nodular shadow rapidly increased its size in a week,
transbronchial fiberoptic examination was performed and lavage fluid was
obtained. The polymerase chain reaction was positive for Mycobacterium avium and
the bacterial growth in culture confirmed the diagnosis. Although tuberculosis is
a well-known adverse reaction to infliximab, development of nontuberculous
mycobacteriosis is quite rare and no such report has so far been published in the
context of infliximab usage. We should be alert to the fact that nontuberculous
mycobacteriosis of slow progression in a usual clinical setting progresses quite
rapidly, thus treatment should not be delayed, especially in patients on
infliximab.
PMID- 17028826
TI - Water intoxication associated with moderate dose of cyclophosphamide pulse
therapy in an elderly patient: a case report and literature review.
AB - Intravenous high-dose cyclophosphamide infusion, usually performed to treat
malignant neoplasms, is known to cause water intoxication. Intravenous
cyclophosphamide pulse therapy (IVCY) is increasingly being employed for the
treatment of rheumatic diseases as well. Recently, water intoxication has been
reported to occur even after low-to-moderate doses of IVCY. In the present paper,
we describe a case of polyarteritis nodosa in a patient in whom water
intoxication developed after IVCY at a moderate dose. Hydration is usually
performed to maintain sufficient urine flow to avoid cystitis. Based on our case
and a review of the literature, it is recommended that hydration should be
carefully performed during IVCY in order to avoid water intoxication, especially
when treating elderly patients.
PMID- 17028827
TI - Systemic lupus erythematosus in identical twins: a case report.
AB - In this report we describe the case of identical twin sisters that developed
systemic lupus erythematosus (SLE). These patients have in common major
histocompatibility complex class I and class II alleles and identical red blood
cell antigens, which is a clear indication of monozygotic twins. Both twins
showed high titers of anti-dsDNA antibody. However, only one of them manifested
signs of lupus psychosis and was positive for the LE test, rheumatoid factor,
anti-Scl 70, anti-SSA, and antiribosomal P antibodies. Both sisters lived
together; therefore, the environmental factors were considered to be the same.
Interestingly, these patients expressed different types of autoantibodies and the
manifestation of disease was also quite different. When one of the twins was
diagnosed with SLE, we began to closely follow up signs of the disease in the
other twin periodically. This enabled us to promptly diagnose the second twin
with SLE and she was successfully treated without progression of the disease. It
is important to mention that following up the subsequent history of an identical
twin diagnosed with SLE allowed early detection of the disease in the other twin.
PMID- 17028828
TI - A case of interstitial cystitis accompanying Sjogren's syndrome.
AB - A 51-year-old woman with interstitial cystitis was referred for screening of
autoimmune disease. She was positive for results of Schirmer and Saxon tests and
for ss/A and ss/B antibodies. Autoantibodies to type 3 muscarinic acetylcholine
receptor were detected in the patient's serum by Western blotting. We diagnosed
her as having interstitial cystitis accompanying Sjogren's syndrome. To enable
early treatment, interstitial cystitis should be considered when patients with
Sjogren's syndrome complain of urinary symptoms.
PMID- 17028829
TI - [Genetic research: chance or risk for health?].
PMID- 17028831
TI - [Federal Environmental Department Commission "Human Biomonitoring": Report of the
Commission].
PMID- 17028832
TI - [Microbiological detection procedures according to Water Supply V 2001. List of
alternative procedures according to 15 Abs. 1 Water Supply V 2001 --1.
Notification of change: Notification of the Federal Environmental Department ].
PMID- 17028836
TI - Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm distal
rule.
PMID- 17028834
TI - Ischemic proctitis following Delorme procedure for external rectal prolapse.
PMID- 17028837
TI - Cell membrane-derived lysophosphatidylcholine activates cardiac ryanodine
receptor channels.
AB - Lysophosphatidylcholine (LPC) is metabolized from a membrane phospholipid and
modulates a variety of channels in the plasma membrane (PM). We examined LPC
modulation of cardiac ryanodine receptor (RyR) channels in the sarcoplasmic
reticulum (SR) using the planar lipid bilayer method to measure the single
channel currents. Micromolar concentrations of LPC increased the open probability
of the reconstituted RyR channels irrespective of whether LPC was added to the
cis or trans chamber. LPC also increased the membrane capacitance of the bilayer.
The effects of LPC contrasted well with those of sphingosylphosphorylcholine
(SPC). Taken together, these results suggest that amphipathic lipid LPC does not
bind directly to the RyR channel protein, but rather, is incorporated into the
bilayer membrane and activates the channel. Thus, we consider cell membrane
derived LPC to be a putative endogenous mediator that activates not only plasma
membrane channels but also RyR channels and induces arrhythmogenic Ca(2+)
mobilization in cardiomyocytes.
PMID- 17028838
TI - Whole-body MR vascular screening detects unsuspected concomitant vascular disease
in coronary heart disease patients.
AB - Coronary heart disease (CHD) patients often show atherosclerotic vascular disease
in other vascular territories. We evaluated how often whole-body MR imaging
detects concomitant arterial pathologies in CHD patients, and how often these
pathologies were not known to the patients previously. Of 4,814 participants in
the population-based Heinz Nixdorf Recall Study, 327 reported CHD (i.e., previous
coronary bypass surgery, angioplasty); of those, 160 patients (mean age 66.4
years) were examined using MR of the brain, the heart (excluding the coronary
arteries), and whole-body MR angiography. The prevalence of each vascular
pathology was assessed, correlated to the others and compared to patients'
histories. Of the 160 CHD patients, 16 (10%) showed MR signs of stroke, and 77
(48.1%) had a stenosis >50% in at least one extracerebral peripheral artery
(other than the coronaries), including 28 (17.5%) with relevant renal artery
stenoses, and 20 (12.5%) with relevant extracerebral internal carotid artery
stenoses. False negative histories were reported in 12 of 81 cases with
myocardial infarctions, and in 11 of 16 cases with cerebrovascular infarctions.
This whole-body atherosclerosis MR screening program allows previously unknown
concomitant vascular disease to be detected in coronary heart disease patients.
Its prospective value should be assessed in further studies.
PMID- 17028839
TI - [Recurring nose bleeds, dyspnea and conspicuous findings in the lung and liver].
PMID- 17028840
TI - [Sturge-Weber syndrome. Early manifestation and visualization of disease course].
AB - BACKGROUND: The purpose of this study was to evaluate ultrasound, MRI, and CT
investigations in children with Sturge-Weber syndrome. PATIENTS AND METHODS: From
1996 to 2005, a total of 15 investigations of the brain performed in 6 children
with Sturge-Weber syndrome were reviewed. We evaluated four ultrasound, five CT,
and six MRI exams. RESULTS: With ultrasound an increase of the echogenicity of
the periventricular white matter was depicted in the first days of life. MRI is
the best modality to demonstrate the vascular malformation, the impaired cerebral
venous drainage, and the atrophy of one hemisphere. CONCLUSIONS: One-sided
periventricular hyperechogenicity on ultrasound can be an early sign of Sturge
Weber syndrome in children with a nevus flammeus. MRI is the method of choice to
diagnose Sturge-Weber syndrome and to follow up these children if the
neurological status of the patients changes.
PMID- 17028841
TI - [Acute lid swelling].
PMID- 17028842
TI - [Relevant secondary findings in magnetic resonance imaging of the heart using the
examples of a bronchial carcinoma and a malignant lymphoma].
AB - BACKGROUND: Here we consider the prevalence of extracardiac findings in the
standard sequences and planning surveys of cardiac MRI. PATIENTS AND METHODS:
Over a period of 2 years, 363 patients (261 men, 102 women) with different
clinical diagnoses were examined by cardiac MRI. The MRI protocol included a
planning survey in three planes and standard sequences in long and short axis
orientation. RESULTS: A total of 53 extracardiac findings were detected: 1
lymphoma, 1 bronchogenic carcinoma, 1 retroperitoneal hematoma, 1 mediastinal
lymphadenopathy, 1 tumor of the adrenal glad, 16 pleural effusions, 14 renal
cysts, 12 liver cysts, 2 pulmonary infiltrate, 1 atelectasis, 2
cholecystolithiasis, 1 diaphragmatic elevation, 1 hiatus hernia. CONCLUSION:
Evaluation of the standard sequences and the planning surveys is useful for
discovering extracardiac findings in a cardiac MRI and should be carried out
routinely.
PMID- 17028844
TI - [Merkel cell carcinoma of the upper lid].
AB - AIMS: Merkel cell carcinoma (MCC) of the skin is a rare form of cutaneous
malignancy of neuroendocrine origin with a propensity to form cutaneous and
lymphogenous metastases. The tumor, affecting predominately elderly patients, has
a significantly higher incidence in female patients (80%) compared to male
patients (20%). The mainstay of therapy is surgical resection with possible
adjuvant radio- or chemotherapy. CASE REPORT: A case of a 78-year-old patient
with a MCC of the upper lid without lymph node involvement or distant metastasis
is described. The tumor was resected and the defect closed by a temporal skin
flap performing a temporary cantholysis. The clinical follow-up revealed an
undisturbed eye lid function without any clinical or radiological signs of a
locoregional or distant recurrence.
PMID- 17028843
TI - [Hyperplasia of the coronoid process: diagnosis and treatment].
AB - STUDY GOAL: As it is an unusual and infrequent clinical entity, hyperplasia of
the coronoid process is often overlooked or diagnosed too late. The aim of this
study was to characterize the morphology, etiology, and clinical picture of
coronoid hyperplasia as well as to discuss its diagnosis and treatment. MATERIALS
AND METHODS: All cases of histologically confirmed hyperplasia of the coronoid
process treated in our center between 1995 and 2004 were analyzed. Patient data
were evaluated with respect to age, gender, clinical symptoms, diagnostic work
up, and treatment. The extracted data were compared to those found in the
literature. RESULTS: The study included 14 new cases and 101 cases already
published: 96 with bilateral and 19 with unilateral hyperplasia. At the time of
diagnosis, the subjects' mean age was 23.7 years. The patients in Bonn were all
treated by coronoidectomy and appropriate physiotherapy. An improvement in mouth
opening could be achieved in 86% of our patients. CONCLUSIONS: In comparison to
the somewhat disappointing results of previously published studies with regard to
mouth opening and mandibular mobility, our treatment concept seems to offer the
possibility for improvement. Our study emphasizes the significance of three
dimensional CT techniques for diagnosis and surgical planning, the superiority of
coronoidectomy over coronoidotomy, and the importance of dynamic physiotherapy to
prevent postoperative scar formation.
PMID- 17028845
TI - [Effects of nicotine with special consideration given to tumorigenesis in the
head and neck region].
AB - BACKGROUND: Tumorigenesis is based on initiation, promotion, and progression,
whereas tobacco smoke is a decisive predisposing factor for squamous cell
carcinomas of the upper aerodigestive tract. A variety of tobacco smoke compounds
is known to potentially initiate tumors, but the alkaloid nicotine is generally
considered to induce addiction only. However, there is growing evidence that
nicotine may also contribute to early stages of tumorigenesis. In the present
study, a possible direct genotoxic potential of nicotine is investigated.
MATERIAL AND METHODS: Lymphatic tissue of the tonsilla palatina of eight donors
was harvested during surgery and incubated with nicotine. DNA damage was measured
with the comet assay. RESULTS: Genotoxic effects of nicotine could be
demonstrated. DISCUSSION: The results suggest a direct contribution of nicotine
to tumor initiation and carcinogenesis.
PMID- 17028847
TI - Protein kinase C isoforms from Giardia duodenalis: identification and functional
characterization of a beta-like molecule during encystment.
AB - Protein kinase C (PKC) is a family of serine/threonine kinases that regulate many
different cellular processes such as cell growth and differentiation in
eukaryotic cells. Using specific polyclonal antibodies raised against mammalian
PKC isoforms, it was demonstrated here for the first time that Giardia duodenalis
expresses several PKC isoforms (beta, delta, epsilon, theta and zeta). All PKC
isoforms detected showed changes in their expression pattern during encystment
induction. In addition, selective PKC inhibitors blocked the encystment in a dose
dependent manner, suggesting that PKC isozymes may play important roles during
this differentiation process. We have characterized here the only conventional
type PKC member found so far in Giardia, which showed an increased expression and
changes in its intracellular localization pattern during cyst formation. The
purified protein obtained by chromatography on DEAE-cellulose followed by size
exclusion chromatography, displayed in vitro kinase activity using histone HI
IIIS as substrate, which was dependent on cofactors required by conventional
PKCs, i.e., phospholipids and calcium. An open reading frame in the Giardia
Genome Database that encodes a homolog of PKCbeta catalytic domain was identified
and cloned. The expressed recombinant protein was also recognized by a mammalian
anti-PKCbeta antibody and was referred as giardial PKCbeta on the basis of all
these experimental evidence.
PMID- 17028846
TI - Urinary F2-isoprostane metabolite levels in children with sleep-disordered
breathing.
AB - Oxidant stress-related mechanisms have been proposed as a major contributor to
the increased prevalence of cardiovascular morbidity in adult patients with sleep
disordered breathing. Isoprostanes provide a reliable biomarker of oxidant injury
in vivo. The purpose of the present study was to examine the hypothesis that
oxidant stress, as evidenced by increased levels of F2-isoprostane metabolites
(IsoP-m) in urine, is present in children with a spectrum of sleep-disordered
breathing. Assays were performed on urinary samples obtained from each of 47
pediatric patients immediately upon awakening after standard overnight
polysomnography. Of the subjects, 15% had mild, 9% had moderate, and 6% had
severe sleep-disordered breathing. After controlling for correlations between BMI
and IsoP-m and SpO2 values, IsoP-m values were unrelated to any polysomnographic
measures. The absence of increased levels of urinary F2-isoprostane metabolites
in children with sleep-disordered breathing suggests that oxidative stress is not
a significant feature of pediatric sleep-disordered breathing.
PMID- 17028848
TI - Capsaicin inhibits catecholamine secretion and synthesis by blocking Na+ and Ca2+
influx through a vanilloid receptor-independent pathway in bovine adrenal
medullary cells.
AB - We report here the effects of capsaicin, a flavoring ingredient in the hot pepper
Capsicum family, on catecholamine secretion and synthesis in cultured bovine
adrenal medullary cells. Capsaicin inhibited catecholamine secretion (IC(50)=9.5,
11.8, and 62 microM) stimulated by carbachol, an agonist of the nicotinic
acetylcholine receptor, by veratridine, an activator of voltage-dependent Na(+)
channels, and by high K(+), an activator of voltage-dependent Ca(2+) channels,
respectively. Capsaicin also suppressed carbachol-induced (22)Na(+) influx
(IC(50)=5.0 microM) and (45)Ca(2+) influx (IC(50)=24.4 muM), veratridine-induced
(22)Na(+) influx (IC(50)=2.4 microM) and (45)Ca(2+) influx (IC(50)=1.1 microM),
and high K(+)-induced (45)Ca(2+) influx (IC(50)=5.8 microM). The reduction in
catecholamine secretion caused by capsaicin was not overcome by increasing the
concentration of carbachol. Furthermore, capsazepine (10 microM), a competitive
antagonist for the transient receptor potential vanilloid 1, and ruthenium red
(30 microM), a nonselective cation channel antagonist, did not block the
inhibition by capsaicin of catecholamine secretion. Capsaicin also suppressed
both basal and carbachol-stimulated (14)C-catecholamine synthesis (IC(50)=10.6
and 26.4 microM, respectively) from [(14)C] tyrosine but not from L: -3, 4
dihydroxyphenyl [3-(14)C] alanine ([(14)C] DOPA) as well as tyrosine hydroxylase
activity (IC(50)=8.4 and 39.0 microM, respectively). The present findings suggest
that capsaicin inhibits catecholamine secretion and synthesis via suppression of
Na(+) and Ca(2+) influx through a vanilloid receptor-independent pathway.
PMID- 17028850
TI - Compositional and technological features of glazed pottery from Aosta Valley
(Italy): a SEM-EDS investigation.
AB - Twelve finds from archaeological excavations carried out in the Aosta region
(Italy) were studied by scanning electron microscopy coupled with energy
dispersive X-ray detection (SEM-EDS). The archaeological samples were shards of
glazed pottery dating from the fourth to the seventh century AD. Analysis of
ceramic bodies revealed a general homogeneity in composition among the studied
samples and the use of a noncalcareous clay for their manufacture; however, two
shards stand out due to their high iron contents. Glazes proved to be high-lead
products with more than 70% PbO in all of the samples investigated but one. For
the latter, a composition poorer in lead and richer in silicon, aluminium and
iron was found. SEM observation of the contact region between body and glaze
suggests that the vitreous coatings were mostly obtained by applying the glazing
components onto the unfired clay body; moreover, a comparison between clay and
glaze compositions suggests the use of a lead compound mixed with a silica-rich
material, not a lead compound by itself.
PMID- 17028849
TI - Comparison of three radioligands for the labelling of human beta-adrenoceptor
subtypes.
AB - We have compared the ability of three radioligands, [(125)I]-cyanopindolol,
[(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol, to label the three human beta
adrenoceptor subtypes. Saturation and competition binding experiments were
performed using membrane preparations from Chinese hamster ovary cells stably
transfected with the three subtypes. While [(3)H]-CGP 12,177 had very similar
affinity for beta(1)- and beta(2)-adrenoceptors (about 40 pM), [(125)I]
cyanopindolol and [(3)H]-dihydroalprenolol had 4- to 6-fold higher affinity for
beta(2)- as compared to beta(1)-adrenoceptors (10 vs 45 and 187 vs 1,021 pM,
respectively). The affinity of [(125)I]-cyanopindolol at beta(3)-adrenoceptors
was considerably lower (440 pM) than at the other two subtypes. The beta(3)
adrenoceptor affinity of [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol was so
low that it could not be estimated within the tested range of radioligand
concentrations (up to 4,000 pM and 30,000 pM for [(3)H]-CGP 12,177 and [(3)H]
dihydroalprenolol, respectively). We conclude that all three radioligands are ill
suited to label beta(3)-adrenoceptors, particularly in preparations co-expressing
multiple subtypes. In the absence of alternatives, [(125)I]-cyanopindolol appears
the least unsuitable to label beta(3)-adrenoceptors. There is a need for high
affinity radioligands which are either selective for beta(3)-adrenoceptors or
reasonably non-selective among all three beta-adrenoceptor subtypes.
PMID- 17028852
TI - Sonographic diagnosis of a common pancreaticobiliary channel in children.
AB - BACKGROUND: A common pancreaticobiliary channel is a very rare condition, but its
diagnosis is of paramount importance since it can lead to complications that can
be prevented. OBJECTIVE: To illustrate the sonographic diagnosis of a common
pancreaticobiliary channel in children referred for abdominal pain or jaundice.
MATERIALS AND METHODS: Four children were diagnosed by ultrasonography and the
diagnosis was subsequently confirmed by MRI. RESULTS: Sonography demonstrated a
pancreaticobiliary junction located in the pancreatic head above the sphincter of
Oddi. This rare congenital anomaly was confirmed in all patients by MRI.
CONCLUSION: A common pancreaticobiliary channel can be diagnosed by sonography.
Nevertheless, our experience is limited, and although sonography can provide an
alert and can assist management, it cannot yet replace MRI.
PMID- 17028853
TI - Diagnostic performance of MRI and MR myelography in infants with a brachial
plexus birth injury.
AB - BACKGROUND: Detailed evaluation of a brachial plexus birth injury is important
for treatment planning. OBJECTIVE: To determine the diagnostic performance of MRI
and MR myelography in infants with a brachial plexus birth injury. MATERIALS AND
METHODS: Included in the study were 31 children with perinatal brachial plexus
injury who underwent surgical intervention. All patients had cervical and
brachial plexus MRI. The standard of reference was the combination of
intraoperative (1) surgical evaluation and (2) electrophysiological studies
(motor evoked potentials, MEP, and somatosensory evoked potentials, SSEP), and
(3) the evaluation of histopathological neuronal loss. MRI findings of cord
lesion, pseudomeningocele, and post-traumatic neuroma were correlated with the
standard of reference. Diagnostic performance characteristics including
sensitivity and specificity were determined. RESULTS: From June 2001 to March
2004, 31 children (mean age 7.3 months, standard deviation 1.6 months, range 4.8
12.1 months; 19 male, 12 female) with a brachial plexus birth injury who
underwent surgical intervention were enrolled. Sensitivity and specificity of an
MRI finding of post-traumatic neuroma were 97% (30/31) and 100% (31/31),
respectively, using the contralateral normal brachial plexus as the control.
However, MRI could not determine the exact anatomic area (i.e. trunk or division)
of the post-traumatic brachial plexus neuroma injury. Sensitivity and specificity
for an MRI finding of pseudomeningocele in determining exiting nerve injury were
50% and 100%, respectively, using MEP, and 44% and 80%, respectively, using SSEP
as the standard of reference. MRI in infants could not image well the exiting
nerve roots to determine consistently the presence or absence of definite
avulsion. CONCLUSION: In children younger than 18 months with brachial plexus
injury, the MRI finding of pseudomeningocele has a low sensitivity and a high
specificity for nerve root avulsion. MRI and MR myelography cannot image well the
exiting nerve roots to determine consistently the presence or absence of avulsion
of nerve roots. The MRI finding of post-traumatic neuroma has a high sensitivity
and specificity in determining the side of the brachial plexus injury but cannot
reveal the exact anatomic area (i.e. trunk or division) involved. The information
obtained is, however, useful to the surgeon during intraoperative evaluation of
spinal nerve integrity for reconstruction.
PMID- 17028855
TI - Strain-dependent expression of four structurally related rat Ly49 receptors;
correlation with NK gene complex haplotype and NK alloreactivity.
AB - Natural killer (NK) cells from certain rat strains promptly kill MHC allogeneic
lymphocytes in vivo, a rejection phenomenon termed allogeneic lymphocyte
cytotoxicity (ALC). ALC can be reproduced in vitro, and is preferentially
mediated by a subset of NK cells expressing the Ly49 stimulatory receptor 3
(Ly49s3) in PVG strain rats. Functional studies have suggested that Ly49s3
triggers NK cell alloreactivity, but its importance relative to other Ly49
receptors has not been investigated. In this study, we have characterized three
rat Ly49 receptors with close sequence similarity to Ly49s3 in the extracellular
region, i.e., Ly49s4, Ly49 inhibitory receptor 3 (Ly49i3), and Ly49i4. Similar to
Ly49s3, Ly49s4 mediated cellular activation while Ly49i4 inhibited NK cytolytic
function. Ly49s4, -i3, and -i4 all reacted with a previously described anti
Ly49s3 monoclonal antibody (mAb) (DAR13), but not a novel mAb (STOK6), which was
shown to be specific for Ly49s3. Expression of these Ly49 receptors varied
markedly between inbred strains, in patterns related to their NK gene complex
(NKC) haplotype, and ability to mediate ALC. Three major groups of NKC haplotypes
could be discerned by restriction fragment length polymorphism analysis. Ly49s3
was present in strains from one of the groups, which corresponded with the "high"
ALC responders. Ly49s3 surface expression was also markedly reduced in the
presence of its putative MHC class Ib ligand(s) in MHC congenic strains. These
data support the notion that Ly49s3 functions as a triggering MHC receptor both
in vitro and in vivo. MHC ligands for the other three Ly49 receptors remain to be
determined.
PMID- 17028856
TI - Two factor H-related proteins from the mouse: expression analysis and functional
characterization.
AB - Complement factor H-related (FHR) proteins display structural and functional
similarities to each other and to the complement regulator factor H (FH). FHRs
have been identified in various species, including human, rat, and the fish
barred sand bass. As mice provide a useful model system to study the
physiological role of FHRs in vivo, we aimed at characterizing murine FHR
proteins. Two putative FHRs of approximately 100 and 38 kDa were detected in
mouse plasma using FH-specific antiserum. In a liver cDNA library, three murine
FHR-encoding transcripts were identified. Two clones code for related FHR
proteins termed FHR-C and FHR-C_v1, which in secreted form are composed of 14 and
13 short consensus repeat (SCR) domains, homologous to SCRs 6-17 and 19-20 of FH.
The third transcript, FHR-B, is derived from a separate gene and codes for a
secreted protein composed of five SCR domains. FHR-B displays homology to SCRs 5
7 and 19-20 of FH. Expression of FHR-B in various tissues was analyzed by real
time polymerase chain reaction and was identified at high levels in liver, kidney
and heart. In liver, FHR-B transcript level was even higher than that of FH. In
addition, FHR-B was expressed as a recombinant 37-kDa protein, and this
recombinant FHR-B interacted with the ligands heparin and human C3b. Using mouse
plasma, the native presumptive FHR proteins were also analyzed in binding assays.
In summary, we identify two FHR proteins in mice and for the first time
characterize a murine FHR as a heparin- and C3b-binding protein.
PMID- 17028857
TI - Radiological and functional assessment of pulmonary involvement in the rheumatoid
arthritis patients.
AB - The aim was to evaluate the findings of high resolution computed tomography
(HRCT) and pulmonary function tests (PFT) in the rheumatoid arthritis (RA)
patients with and without pulmonary symptoms and to determine their role in
prediction of respiratory system involvement. Among 54 consecutive RA patients,
22 (41%) were symptomatic and 32 (59%) were asymptomatic after detailed
respiratory examination. Abnormal findings in PFTs were present in 10 (45%)
symptomatic and 15 (47%) asymptomatic patients. PFT results were similar in both
groups. A total of 18 (82%) symptomatic and 16 (50%) asymptomatic patients had
abnormalities in HRCT scans. About 16 (80%) of 20 patients with normal HRCT scans
had no pulmonary symptoms at all and we noted a significant correlation (P <
0.05). HRCT was more useful mean than PFTs in evaluation of pulmonary involvement
in the RA patients; however, no correlation was present between various
respiratory symptoms and abnormal findings both in PFTs and HRCT scans.
PMID- 17028858
TI - Enhanced oxidative status but not corresponding elevated antioxidative status by
anticardiolipin antibody and disease activity in patients with systemic lupus
erythematosus.
AB - Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis,
and an increased susceptibility of plasma lipids and lipoproteins to oxidation
could at least in part promote atherogenesis. The objective of this study was to
identify the effects of anticardiolipin antibody (aCL) and disease activity on
oxidative and antioxidative status in patients with SLE. In this study, patients
in SLE/aCL+ group and in SLE disease activity index >3 group had significantly
higher thiobarbituric acid reactive substance (TBARS) levels, titers of
autoantibodies against oxidized low-density lipoprotein (ox-LDL), and glutathione
peroxidase activity than that of healthy controls. However, only TBARS and titers
of autoantibodies against ox-LDL but not antioxidant enzyme activities were
significantly different between SLE subgroups. Thus, enhanced oxidative status
but not corresponding elevated antioxidative status by the presence of aCL and
active disease activity make potent antioxidant therapy valuable for these SLE
patients in preventing oxidative damage.
PMID- 17028859
TI - Which of the three different tender points assessment methods is more useful for
predicting the severity of fibromyalgia syndrome?
AB - Digital palpation, myalgic scoring and dolorimetry are frequently used to count
tender points in fibromyalgia syndrome. We aimed to investigate the probable
relation between tender points count and fibromyalgia impact questionnaire and to
assess which of the tender point counting methods is the most successful in
predicting the severity of the disease. Tender point areas of 36 patients with
fibromyalgia syndrome were assessed with three methods which are myalgic scoring,
digital and dolorimetric tender points counting methods. Fibromyalgia impact
questionnaire was used to measure the disease severity. The correlation between
each of the assessment methods and fibromyalgia impact questionnaire was
investigated. The mean count of digitally evaluated tender points was 14.86 +/-
2.67 and by dolorimetry was 11.81 +/- 4.48. The mean total myalgic score was
found to be 24.61 +/- 8.91. All of the tender point evaluation methods correlated
positively with each other (P < 0.01). Fibromyalgia impact questionnaire score
was also correlated with only digital palpation tender point count of these three
evaluation methods (r = 0.427, P < 0.05). Digital tender point count seemed to be
sufficient for assessment, and there is no need for an additional instrument for
tender point evaluation.
PMID- 17028860
TI - A case of pure red cell aplasia and systemic lupus erythematosus caused by human
parvovirus B19 infection.
AB - Human parvovirus B19 (B19) rarely induces pure red cell aplasia (PRCA) in healthy
hosts. Meanwhile B19 infection is often clinically similar to systemic lupus
erythematosus (SLE), and several cases have been reported wherein B19 actually
stimulated SLE exacerbation in an immunocompetent subject. An 82-year-old healthy
woman was diagnosed to have complicated with B19 infection and PRCA. Four weeks
later, she had high fever, polyarthritis, and oral ulcers, additionally diagnosed
with SLE, and subsequently, 15 mg of prednisone was started. This is the first
case wherein B19 infection caused both PRCA and SLE in a healthy patient as far
as our investigations are concerned.
PMID- 17028861
TI - MRI in psoriatic arthritis with hand and foot involvement.
AB - Evaluation of MRI-findings in patients with involvement of psoriatic arthritis
(PsA) in small joints in hands and feet. Twenty-five patients with symptomatic
joint involvement were studied by MRI. All patients were found to be positive for
one or more imaging criteria. Soft tissue oedema was identified in 22/25 (88%)
patients. Joint effusion was observed in 23/25 (92%) patients, whereas bone
erosion was seen in 20/25 (80%) patients. Bone marrow oedema was evident in 21/25
(84%) cases. In 12/25 (48%) cases, bone proliferation was noted. Tendon sheath
effusion was present in 17/25 (68%) patients. Contrast enhancement of the synovia
was detected in all patients (n = 25) (100%), whereas adjacent periost was
enhanced in 22/25 (88%) and epiphysial bone marrow in 18/25 (72%) patients. MRI
allows the assessment of PsA-alterations of soft tissue, cartilage, bone, bone
marrow, and adjacent tendon sheath in patients with hand and foot involvement.
PMID- 17028862
TI - The incidence of new onset congestive heart failure and heart failure
exacerbation in Veteran's Affairs patients receiving tumor necrosis factor alpha
antagonists.
AB - The objective of this study was to evaluate the incidence of new onset or
worsening congestive heart failure in Veteran's Affairs (VA) patients who have
received infliximab, etanercept, or adalimumab, and to compare mortality rates in
these patients to control populations. We enrolled three groups of patients for
this retrospective study: TNF-alpha group (n = 103), a rheumatoid arthritis (RA)
control group (n = 100), and a control group without RA (n = 100). All patients
at our VA facility who had received at least one dose of the TNF-alpha
antagonists were included in the TNF-alpha group. Admissions for CHF did not
differ between the three groups: TNF-alpha 7 (6.7%), RA control 8 (8%), non-RA
control 7 (7%); P = 0.940. Mortality rates were not significantly different: TNF
alpha 4 (3.8%), RA control 7 (7%), non-RA control 11 (11%); P = 0.147. Our study
showed no difference between the three groups in either CHF exacerbation or
mortality.
PMID- 17028863
TI - Matrix metalloproteinases and their inhibitors in the chamber angle of normal
eyes and patients with primary open-angle glaucoma and exfoliation glaucoma.
AB - BACKGROUND: In glaucoma, extensive pathological changes occur in the trabecular
meshwork (TM) and juxtacanalicular tissue of the chamber angle. Aqueous humor
drainage is disturbed due to the accumulation of extracellular matrix (ECM)
material in the outflow system. Matrix metalloproteinases (MMPs) remodel ECM
material and, thus, they may have a role in regulating outflow facility and
intraocular pressure (IOP). This study examined the expression of MMPs and tissue
inhibitors of MMPs (TIMPs) in the chamber angle of normal eyes and in primary
open-angle glaucoma (POAG) and in exfoliation glaucoma (ExG). METHODS: TM tissues
were isolated from healthy donor eyes for corneal transplantation. Specimens of
the inner wall of Schlemm's canal and the juxtacanalicular tissue were collected
from patients with POAG or ExG during deep sclerectomy operation. Monoclonal
antibodies against MMPs (MMP-1, -2, -3, and -9) and antibodies against TIMPs
(TIMP-1, -2, and -3) were used for immunohistochemical staining. RESULTS:
Immunoreactivity for MMP-2, TIMP-2, or TIMP-3 was observed in human normal TM and
in the inner wall of Schlemm's canal. In general, immunoreactions for all of the
tested MMPs were more intense in POAG samples than in ExG samples or in the
control group. The only exception was the MMP-2 level, which was the highest in
the control group. The staining intensity of MMP-1 or MMP-3 was significantly
higher in POAG when compared to ExG. TIMP-1 was significantly increased in POAG
compared with ExG and there were no marked differences in the levels of TIMP-2 or
TIMP-3 between POAG and ExG. The ratios of MMP-1/TIMP-1 and MMP(1+2+3+9) and
TIMP(1+2+3) were significantly higher in samples from POAG compared to those of
ExG. CONCLUSIONS: Our results reveal an expression imbalance between MMPs and
their endogenous tissue inhibitors in tissue samples from patients with POAG and
ExG. Differences in immunohistochemical reactions reflect discrete local
pathogenic mechanisms involved in POAG and ExG. With respect to the proposed role
of MMPs in the remodeling of ECM material, this may point to a weaker reactivity
to the accumulation of ECM material in TM in ExG than POAG eyes.
PMID- 17028865
TI - Bayesian data mining of protein domains gives an efficient predictive algorithm
and new insight.
AB - Identification of structural domains in uncharacterized protein sequences is
important in the prediction of protein tertiary folds and functional sites, and
hence in designing biologically active molecules. We present a new predictive
computational method of classifying a protein into single, two continuous or two
discontinuous domains using Bayesian Data Mining. The algorithm requires only the
primary sequence and computer-predicted secondary structure. It incorporates
correlation patterns between certain 3-dimensional motifs and some local helical
folds found conserved in the vicinity of protein domains with high statistical
confidence. The prediction of domain-class by this computationally simple and
fast method shows good accuracy of prediction-average accuracies 83.3% for single
domain, 60% for two continuous and 65.7% for two discontinuous domain proteins.
Experiments on the large validation sample show its performance to be
significantly better than that of DGS and DomSSEA. Computations of Bayesian
probabilities show important features in terms of correlation of certain
conserved patterns of secondary folds and tertiary motifs and give new insight.
Applications for improved accuracy of predicting domain boundary points relevant
to protein structural and functional modeling are also highlighted.
PMID- 17028864
TI - Molecular characterization of deletion breakpoints in adults with 22q11 deletion
syndrome.
AB - 22q11 Deletion syndrome (22q11DS) is a common microdeletion syndrome with
variable expression, including congenital and later onset conditions such as
schizophrenia. Most studies indicate that expression does not appear to be
related to length of the deletion but there is limited information on the
endpoints of even the common deletion breakpoint regions in adults. We used a
real-time quantitative PCR (qPCR) approach to fine map 22q11.2 deletions in 44
adults with 22q11DS, 22 with schizophrenia (SZ; 12 M, 10 F; mean age 35.7 SD 8.0
years) and 22 with no history of psychosis (NP; 8 M, 14 F; mean age 27.1 SD 8.6
years). QPCR data were consistent with clinical FISH results using the TUPLE1 or
N25 probes. Two subjects (one SZ, one NP) negative for clinical FISH had atypical
22q11.2 deletions confirmed by FISH using the RP11-138C22 probe. Most (n = 34; 18
SZ, 16 NP) subjects shared a common 3 Mb hemizygous 22q11.2 deletion. However,
eight subjects showed breakpoint variability: a more telomeric proximal
breakpoint (n = 2), or more centromeric (n = 3) or more telomeric distal
breakpoint (n = 3). One NP subject had a proximal nested 1.4 Mb deletion. COMT
and TBX1 were deleted in all 44 subjects, and PRODH in 40 subjects (19 SZ, 21
NP). The results delineate proximal and distal breakpoint variants in 22q11DS.
Neither deletion extent nor PRODH haploinsufficiency appeared to explain the
clinical expression of schizophrenia in the present study. Further studies are
needed to elucidate the molecular basis of schizophrenia and clinical
heterogeneity in 22q11DS.
PMID- 17028866
TI - Severe metallosis after unicompartmental knee arthroplasty.
AB - We report on a case of a patient who had femoral osteolysis and severe metallosis
of the knee joint resulting from the secondary abrasive wear of the metal-backed
tibial component of a unicompartmental knee arthroplasty due to massive wear of
tibial polyethylene. The failure was diagnosed 11 years after implantation. This
metallosis affected the intra-articular tissues and the subchondral bone.
PMID- 17028867
TI - Sclerosing polidocanol injections to treat chronic painful shoulder impingement
syndrome-results of a two-centre collaborative pilot study.
AB - The histological changes found in the supraspinatus tendon have similarities with
the findings in Achilles-, patellar- and extensor carpi radialis brevis (ECRB)
tendinopathy. In recent studies, we have found a vasculo-neural ingrowth in
chronic painful Achilles and patellar tendinopathy, and demonstrated good short
term clinical effects with injections of the sclerosing substance polidocanol. In
this collaborative two-centre pilot study, 15 patients (10 males and 5 females,
mean age 46 years) with a long duration of shoulder pain (mean 28 months), and
given the diagnosis chronic painful shoulder impingement syndrome, were included.
They had tried rest, traditional rehabilitation exercises and multiple
subacromial corticosteroid injections, without effect. We found vascularity
(neovessels) in chronic painful, but not in pain-free, supraspinatus tendons, and
prospectively studied the clinical effects of ultrasound (US) and colour Doppler
(CD)-guided injections of polidocanol, targeting the area with neovessels. The
patients evaluated the amount of shoulder pain during horizontal shoulder
activity on a visual analogue scale (VAS), and satisfaction with treatment. Two
(median) (range 1-5) polidocanol treatments (with 4-8 weeks in between) were
given. In four patients (considered treatment failure), cortisone was injected
into an inflamed subacromial bursa at one separate occasion weeks after the last
polidocanol injection. At follow-up, 8 (median) (range 4-17) months after the
treatment, 14 patients were satisfied with the result. Using the visual analogue
scale evaluation (VAS), the pain dropped from 79 before treatment to 21 at follow
up (P < 0.05). In the short-term perspective, sclerosing polidocanol injections
targeting the neovessels in the supraspinatus tendon and/or bursa wall seems to
have a potential to reduce the pain during shoulder loading activity.
PMID- 17028868
TI - The Oxford phase III unicompartmental knee replacement in patients less than 60
years of age.
AB - Treatment of younger patients with medial unicompartmental disease of the knee
joint remains a challenging therapeutic dilemma. With the refinement of implant
design, fixation and the minimally invasive techniques employed with
unicompartmental knee replacement, indications have expanded to include its use
in young patients. A prospective cohort of 46 unicompartmental knee procedures
were performed with a 2-year minimum and 6-year maximum follow-up, using the
Oxford phase III unicompartmental knee arthroplasty, in the younger patient group
(age 60 or younger). We conclude that the unicompartmental knee arthroplasty is
an important option for the treatment of medial compartment disease for patients
60 years or younger. Obesity can cause technical difficulties, increased risk of
complications and early failure of this prosthesis.
PMID- 17028869
TI - Second-look arthroscopic findings of 208 patients after ACL reconstruction.
AB - The aim of this study is to report the arthroscopic subjective findings of
reconstructed anterior cruciate ligament (ACL) with good clinical outcome. Graft
used for reconstruction was either patella bone-tendon-bone (PBTB) autograft or
hamstring tendon [quadrupled semitendinous and gracilis tendon (QSGT)] autograft.
From March 1997 to September 2003, among 716 ACL reconstructions 209 knees (208
patients) were available for second-look arthroscopy at a mean 21.2-month (range,
14-70 months) postoperative period. The second-look arthroscopy focused on the
evaluation of (1) continuity of the reconstructed ACL graft, (2) subjective graft
tension using a probe, (3) the extent of synovial coverage, (4) the prevalence of
cyclops or cyclops-like lesion, and (5) bony change after notchplasty. Patellar
tendon autograft was used in 80 knees, hamstring tendon autograft in 129 knees.
Just prior to second-look arthroscopy two objective clinical evaluations, KT-2000
arthrometer and Lysholm knee score, were performed to verify good clinical
outcomes. A comparison between the hamstring tendon group and the patella tendon
group, hamstring group showed slightly better results in Lysholm knee scores and
KT-2000 arthrometer but there were no statistically significant differences
(p>0.05). Undetected partial graft tear was seen in 21 knees (10%). With regard
to graft tension, a total of 181 grafts (87%) showed normal tension and 28 (13%)
showed slight lax tension. The overall synovial coverage was poor in nine (4%)
knees. The synovial coverage was slightly better in the hamstring tendon group. A
total of 45 knees (21.5%) showed cyclops-like lesion in variable sizes and
locations. Reformation of the notch was seen in 85 knees (40%). In conclusion,
the findings of second-look arthroscopy of reconstructed ACL in good clinical
outcome patients showed approximately 10% partial graft tear, 5% poor synovial
coverage, 20% cyclops-like lesion, and 40% some notch reformation.
PMID- 17028870
TI - Distribution of extracellular polymeric substances in aerobic granules.
AB - Extracellular matrix provides an architectural structure and mechanical stability
for aerobic granules. Distributions of cells and extracellular polymeric
substances (EPS), including proteins, alpha- and beta-D-glucopyranose
polysaccharides, in acetate-fed granules and phenol-fed granules were probed
using a novel quadruple staining scheme. In acetate-fed granules, protein and
beta-D-glucopyranose polysaccharides formed the core, whereas, the cells and
alpha-D-glucopyranose polysaccharides accumulated in the granule outer layers.
Based on these experimental findings, this study indicated that different
conclusions can be obtained regarding EPS distributions when granules were
stained differently. The core of phenol-fed granules, conversely, was formed
principally by proteins; whereas, the cells and alpha- and beta-D-glucopyranose
polysaccharides were accumulated at an outer filamentous layer. Using a series of
confocal laser scanning microscope (CLSM) images whose threshold values were
determined via Otsu's scheme, the three-dimensional distributions of cells and
EPS were produced using a polygonal surface model. Structural information
extracted can be applied in further development of comprehensive granule models.
PMID- 17028871
TI - Expression and secretion of a single-chain sweet protein monellin in Bacillus
subtilis by sacB promoter and signal peptide.
AB - The sweet protein monellin gene was expressed in Bacillus subtilis under the
control of the Bacillus subtilis sacB promoter and signal peptide sequence. A 294
bp DNA fragment, coding for sweet protein monellin, was ligated into the
Escherichia coli/B. subtilis shuttle vector pHPC, producing pHPMS, which was
subsequently transformed into B. subtilis QB1098, DB104, and DB403. The peptide
efficiently directed the secretion of monellin from the recombinant B. subtilis
cells. A maximum yield of monellin of 0.29 g protein l(-1) was obtained from the
supernatant of B. subtilis DB403 harboring pHPMS. SDS-PAGE confirmed the purity
of the recombinant product.
PMID- 17028872
TI - Synthesis of DL-tryptophan by modified broad specificity amino acid racemase from
Pseudomonas putida IFO 12996.
AB - Broad specificity amino acid racemase (E.C. 5.1.1.10) from Pseudomonas putida IFO
12996 (BAR) is a unique racemase because of its broad substrate specificity. BAR
has been considered as a possible catalyst which directly converts inexpensive L
amino acids to DL-amino acid racemates. The gene encoding BAR was cloned to
utilize BAR for the synthesis of D-amino acids, especially D-Trp which is an
important intermediate of pharmaceuticals. The substrate specificity of cloned
BAR covered all of the standard amino acids; however, the activity toward Trp was
low. Then, we performed random mutagenesis on bar to obtain mutant BAR
derivatives with high activity for Trp. Five positive mutants were isolated after
the two-step screening of the randomly mutated BAR. After the determination of
the amino acid substitutions in these mutants, it was suggested that the
substitutions at Y396 and I384 increased the Trp specific racemization activity
and the racemization activity for overall amino acids, respectively. Among the
positive mutants, I384M mutant BAR showed the highest activity for Trp. L-Trp (20
mM) was successfully racemized, and the proportion of D-Trp was reached 43% using
I384M mutant BAR, while wild-type BAR racemized only 6% of initial L-Trp.
PMID- 17028873
TI - Methanol utilizing Desulfotomaculum species utilizes hydrogen in a methanol-fed
sulfate-reducing bioreactor.
AB - A sulfate-reducing bacterium, strain WW1, was isolated from a thermophilic
bioreactor operated at 65 degrees C with methanol as sole energy source in the
presence of sulfate. Growth of strain WW1 on methanol or acetate was inhibited at
a sulfide concentration of 200 mg l(-1), while on H2/CO2, no apparent inhibition
occurred up to a concentration of 500 mg l(-1). When strain WW1 was co-cultured
under the same conditions with the methanol-utilizing, non-sulfate-reducing
bacteria, Thermotoga lettingae and Moorella mulderi, both originating from the
same bioreactor, growth and sulfide formation were observed up to 430 mg l(-1).
These results indicated that in the co-cultures, a major part of the electron
flow was directed from methanol via H2/CO2 to the reduction of sulfate to
sulfide. Besides methanol, acetate, and hydrogen, strain WW1 was also able to use
formate, malate, fumarate, propionate, succinate, butyrate, ethanol, propanol,
butanol, isobutanol, with concomitant reduction of sulfate to sulfide. In the
absence of sulfate, strain WW1 grew only on pyruvate and lactate. On the basis of
16S rRNA analysis, strain WW1 was most closely related to Desulfotomaculum
thermocisternum and Desulfotomaculum australicum. However, physiological
properties of strain WW1 differed in some aspects from those of the two related
bacteria.
PMID- 17028874
TI - Genomic adaptation of ethanologenic yeast to biomass conversion inhibitors.
AB - One major barrier to the economic conversion of biomass to ethanol is inhibitory
compounds generated during biomass pretreatment using dilute acid hydrolysis.
Major inhibitors such as furfural and 5-hydroxymethylfurfural (HMF) inhibit yeast
growth and subsequent fermentation. The ethanologenic yeast Saccharomyces
cerevisiae demonstrated a dose-dependant inhibition by the inhibitors and has the
potential to transform furfural and HMF into less toxic compounds of furfuryl
alcohol and 2,5-bis-hydroxymethylfuran (also termed as furan-2,5-dimethanol
(FDM)), respectively. For a sustainable and cost-competitive biomass-to-ethanol
industry, it is important to develop more tolerant yeast strains that can, in
situ, detoxify the inhibitors and produce ethanol. This study summarizes current
knowledge and our understanding of the inhibitors furfural and HMF and discusses
metabolic conversion pathways of the inhibitors and the yeast genomic expression
response to inhibitor stress. Unlike laboratory strains, gene expression response
of the ethanologenic yeast to furfural and HMF was not transient, but a continued
dynamic process involving multiple genes at the genome level. This suggests that
during the lag phase, ethanologenic yeasts undergo a genomic adaptation process
in response to the inhibitors. The findings to date provide a strong foundation
for future studies on genomic adaptation and manipulation of yeast to aid more
robust strain design and development.
PMID- 17028875
TI - Monoterpenes as novel substrates for oxidation and halo-hydroxylation with
chloroperoxidase from Caldariomyces fumago.
AB - Chloroperoxidase (CPO) from Caldariomyces fumago was analysed for its ability to
oxidize ten different monoterpenes with hydrogen peroxide as oxidant. In the
absence of halide ions geraniol and, to a lesser extent, citronellol and nerol
were converted into the corresponding aldehydes, whereas terpene hydrocarbons did
not serve as substrates under these conditions. In the presence of chloride,
bromide and iodide ions, every terpene tested was converted into one or more
products. (1S)-(+)-3-carene was chosen as a model substrate for the CPO-catalysed
conversion of terpenes in the presence of sodium halides. With chloride, bromide
and iodide, the reaction products were the respective (1S,3R,4R,6R)-4-halo-3,7,7
trimethyl-bicyclo[4.1.0]-heptane-3-ols, as identified by 1H and 13C nuclear
magnetic resonance. These product formations turned out to be strictly regio- and
stereoselective and proceeded very rapidly and almost quantitatively. Initial
specific activities of halohydrin formation increased from 4.22 U mg-1 with
chloride to 12.22 U mg-1 with bromide and 37.11 U mg-1 with iodide as the
respective halide ion. These results represent the first examples of the
application of CPO as a highly efficient biocatalyst for monoterpene
functionalization. This is a promising strategy for 'green' terpene chemistry
overcoming drawbacks usually associated with cofactor-dependent oxygenases, whole
cell biocatalysts and conventional chemical methods used for terpene conversions.
PMID- 17028876
TI - Biological nitrogen removal with nitrification and denitrification via nitrite
pathway.
AB - Presently, the wastewater treatment practices can be significantly improved
through the introduction of new microbial treatment technologies. To meet
increasingly stringent discharge standards, new applications and control
strategies for the sustainable removal of ammonium from wastewater have to be
implemented. Partial nitrification to nitrite was reported to be technically
feasible and economically favorable, especially when wastewater with high
ammonium concentrations or low C/N ratios is treated. For successful
implementation of the technology, the critical point is how to maintain partial
nitrification of ammonium to nitrite. Partial nitrification can be obtained by
selectively inhibiting nitrite oxidizing bacteria through appropriate regulation
of the system's DO concentration, microbial SRT, pH, temperature, substrate
concentration and load, operational and aeration pattern, and inhibitor. The
review addressed the microbiology, its consequences for their application, the
current status regarding application, and the future developments.
PMID- 17028877
TI - Production of red mold rice using a modified Nagata type koji maker.
AB - In this research, a commercial koji maker with a rotary perforated bed of 5-m
diameter was modified for red mold rice production. Monascus purpureus BCRC 31499
was selected for its high production capacities of monacolin K and red pigment.
The selected strain was first cultivated in a 120-l submerged type fermentor at
34 degrees C and 2 vvm aeration rate with 60 rpm agitation for 5 days using 20%
liquefied rice porridge as carbon source. The high concentration red mold rice
broth (>3.5 g/ml) was harvested for inocula and well mixed with cooked rice to an
initial concentration of 2% v/w. The inoculated cooked rice then was directed
into the modified koji maker, in which temperature and humidity profiles were
kept at varied levels at different stages, respectively. Air was circulated to
remove fermentation heat while the perforated bed rotated slowly for providing
mild agitation. Lag phase of the Monascus sp. in the modified koji maker was
determined to be 16 h by the time the koji temperature raised rapidly. Water was
added into the koji bed by a water curtain at the 36th hour to keep the moisture
content of the rice koji at 50% or above. At the final stage, temperature was
adjusted to 34 degrees C to direct red pigment production. After 7 days, 1,200-kg
high quality red mold rice was harvested per batch. Labor costs, space, and
fermentation time were reduced tremendously compared with those made by
traditional methods.
PMID- 17028878
TI - A case of split cord malformation associated with myeloschisis.
AB - INTRODUCTION: Split cord malformation (SCM) associated with myeloschisis is a
very rare form of spinal dysraphism. We encountered a case of SCM associated with
myeloschisis showing split neural placodes (hemicords) in the upper lumbar
region. RESULTS: Radiological examinations, including prenatal MRI and postnatal
CT scan, clearly demonstrated a bony spur between the two hemicords as well as
myeloschisis, which facilitated a precise preoperative diagnosis of this complex
anomaly. Resection of the spur, closure of the myeloschisis, and untethering of
the thickened filum terminale were successfully accomplished in one stage. The
presence of SCM associated with myeloschisis is consistent with the hypothesis of
an ontogenic basis of neural development, and we emphasize the importance of
early imaging including prenatal MRI for diagnosing this complex anomaly.
PMID- 17028879
TI - The Strata programmable valve for shunt-dependent hydrocephalus: the pediatric
experience at a single institution.
AB - BACKGROUND AND OBJECTIVE: The Medtronic PS Medical Strata valve has pressure flow
characteristics that are noninvasively adjusted with a magnetic tool. The
objective of this study was to examine its efficacy during our initial experience
with it in shunt-dependent children. MATERIALS AND METHODS: A retrospective
review of 53 children with a median age of 2.0 years who had 61 Strata valves
implanted. CONCLUSION: The Strata valve is efficacious in the treatment of shunt
dependant hydrocephalus in children. The 1-year shunt survival rate of 67.2% is
comparable to that previously reported from a multicenter trial. Of the 30
therapeutically aimed adjustments during the study period, 16 (53.3%) resulted in
improvement in abnormal signs or symptoms. Our data indicate that adjustments can
be used to treat signs or symptoms of cerebrospinal fluid overdrainage or
underdrainage, which may obviate the need for additional surgery.
PMID- 17028880
TI - Diastematomyelia in children: treatment outcome and natural history of associated
syringomyelia.
AB - OBJECTIVE: To quantify the long-term outcome of children with diastematomyelia
and the implication of syringomyelia in the natural history. MATERIALS:
Retrospective study of 17 children (nine girls and eight boys) with
diastematomyelia operated during 1989-2004. Mean age at diagnosis was 3.4 years
(range 5 days-12 years), mean follow-up was 5 years; 14 had excision of spur and
cord untethering, 3 had excision of spur alone. RESULTS: The bony spur was in the
lumbar region in 12 and thoracic in 5 patients. Syringomyelia was present in
eight (47%), associated with bony spur between L1 and 4 (p=0.088), spina bifida
occulta in ten (58.8%), and spinal lipoma in one (6%). Preoperative Necker
Enfants Malades (NEM) scores were 17 in eight patients, 16 in four, 15 in three,
13 in one, and 12 in one patient. Presenting neurological deficits were motor in
eight, sensory deficits in three, and anal incontinence in one patient. There was
improvement of NEM scores postoperatively in five patients only, but still with
residual deficit. Repeat spur excision and cord untethering was performed in
three patients for neurological deterioration 1-4 years after first operation. On
postoperative MRI scans syringomyelia remained unchanged in all eight patients.
There were one skin infection, one transient motor deterioration, and one patient
with sensory deficit after surgery. CONCLUSION: Prophylactic operations were
associated with the best clinical outcome. Despite improvement, all patients with
established preoperative deficit still had residual neurological deficits at
their last follow-up. The associated syringomyelia remained unchanged after
surgery, indicating that it does not contribute to the neurological syndrome.
PMID- 17028881
TI - Management of blunt tracheal trauma in children: a case series and review of the
literature.
AB - Blunt tracheal trauma seldom develops in children because of their anatomy and
the mobility of the cartilage. It has the potential to be overlooked, either
because of the severity of concomitant injuries or because of the unfamiliarity
of paediatricians with this type of injury. However, tracheal injury might be
lethal due to airway compromise. Early bronchoscopy may be necessary to
anticipate complications and prevent permanent dysfunction. We present a
retrospective, double-institution case series over a 5-year period, describing
five children, aged 3 to 14 years, with tracheal injury after blunt cervical
trauma. All patients showed emphysema with pneumomediastinum. After explorative
bronchoscopy, all patients were successfully treated with antibiotics and/or
supportive ventilation. In summary, minimal lesions due to blunt tracheal trauma
could be treated conservatively in children. Since the external signs of tracheal
injury are not indicative of the extent of the trauma, a high index of suspicion
is warranted in these patients.
PMID- 17028882
TI - Strategies to screen for adrenal suppression in children with asthma should take
account of compliance with inhaled corticosteroids.
PMID- 17028883
TI - Use of psychotropic medications in Italian children and adolescents.
AB - INTRODUCTION: The evidence of psychotropic drug safety and efficacy in the
pediatric population is scant and widely debated. Yet, the prescription
prevalence and incidence are increasing. A drug utilization study, based on a
multiregional prescription database was therefore carried out in a sample of
1,484,770 Italian children and adolescents younger than 18 years during the year
2004. Furthermore, the trend of psychotropic prescription prevalence was
evaluated from 1998 to 2004. During 2004, 4,316 children and adolescents received
psychotropic drugs (2.91 per thousand youths). Antidepressants were prescribed to
3,503 youths (2.36 per thousand), antipsychotics to 1,005 (0.68 per thousand),
and lithium to 73 (0.05 per thousand). A total of 265 youths received drugs from
more than one psychotropic class. The prevalence rate of psychotropic drug
prescriptions increased with increasing age, with a statistically significant
trend ([Formula: see text]; p<0.0001), and it increased in the period 1998-2004
with a statistically significant trend ([Formula: see text]; p<0.0001), reaching
its highest value in 2002 (3.08 per thousand). The trend for antidepressants was
similar ([Formula: see text]; p<0.0001), while the prevalence of antipsychotics
did not increase. CONCLUSION: Even though the prevalence of psychotropic drug
prescriptions in Italian children is lower than that reported in other countries
(e.g. United States, Canada, Netherlands, UK), the increase in antidepressant
prescriptions raises some concerns. Data concerning safety and efficacy of these
antidepressants in pediatrics are still limited and further studies are needed to
guarantee evidence based therapeutic approaches in children, adolescents and
their families.
PMID- 17028884
TI - Extending the mirror neuron system model, I. Audible actions and invisible
grasps.
AB - The paper introduces mirror neuron system II (MNS2), a new version of the MNS
model (Oztop and Arbib in Biol Cybern 87 (2):116-140, 2002) of action recognition
learning by mirror neurons of the macaque brain. The new model uses a recurrent
architecture that is biologically more plausible than that of the original model.
Moreover, MNS2 extends the capacity of the model to address data on audio-visual
mirror neurons and on the response of mirror neurons when the target object was
recently visible but is currently hidden.
PMID- 17028885
TI - Do geomagnetic storms change the behaviour of the stingless bee guirucu
(Schwarziana quadripunctata)?
AB - Six behavioural experiments were carried out to investigate the magnetic field
effects on the nest-exiting flight directions of the honeybee Schwarziana
quadripunctata (Meliponini). No significant differences resulted during six
experiment days under varying geomagnetic field and the applied static
inhomogeneous field (about ten times the geomagnetic field) conditions. A
surprising statistically significant response was obtained on a unique magnetic
storm day. The magnetic nanoparticles in these bees, revealed by ferromagnetic
resonance, could be involved in the observed effect of the geomagnetic storm.
PMID- 17028887
TI - Adaptive-filtering of trisomy 21: risk of Down syndrome depends on family size
and age of previous child.
AB - The neonatal incidence rate of Down syndrome (DS) is well-known to accelerate
strongly with maternal age. This non-linearity renders mere accumulation of
defects at recombination during prolonged first meiotic prophase implausible as
an explanation for DS rate increase with maternal age, but might be anticipated
from chromosomal drive (CD) for trisomy 21. Alternatively, as there is selection
against genetically disadvantaged embryos, the screening system that eliminates
embryos with trisomy 21 might decay with maternal age. In this paper, we provide
the first evidence for relaxed filtering stringency (RFS) to represent an
adaptive maternal response that could explain accelerating DS rates with maternal
age. Using historical data, we show that the proportion of aberrant live births
decrease with increased family size in older mothers, that inter-birth intervals
are longer before affected neonates than before normal ones, and that primiparae
exhibit elevated levels of DS incidence at higher age. These findings are
predicted by adaptive RFS but cannot be explained by the currently available
alternative non-adaptive hypotheses, including CD. The identification of the
relaxation control mechanism and therapeutic restoration of a stringent screen
may have considerable medical implications.
PMID- 17028886
TI - Women infected with parasite Toxoplasma have more sons.
AB - The boy-to-girl ratio at birth (secondary sex ratio) is around 0.51 in most
populations. The sex ratio varies between societies and may be influenced by many
factors, such as stress and immunosuppression, age, primiparity, the sex of the
preceding siblings and the socioeconomic status of the parents. As parasite
infection affects many immunological and physiological parameters of the host, we
analyzed the effect of latent toxoplasmosis on sex ratios in humans. Clinical
records of 1,803 infants born from 1996 to 2004 contained information regarding
the mother's age, concentration of anti-Toxoplasma antibodies, previous
deliveries and abortions and the sex of the newborn. The results of our
retrospective cohort study suggest that the presence of one of the most common
parasites (with a worldwide prevalence from 20 to 80%), Toxoplasma gondii, can
influence the secondary sex ratio in humans. Depending on the antibody
concentration, the probability of the birth of a boy can increase up to a value
of 0.72, C.I.95 = (0.636, 0.805), which means that for every 260 boys born, 100
girls are born to women with the highest concentration of anti-Toxoplasma
antibodies. The toxoplasmosis associated with immunosuppression or
immunomodulation might be responsible for the enhanced survival of male embryos.
In light of the high prevalence of latent toxoplasmosis in most countries, the
impact of toxoplasmosis on the human population might be considerable.
PMID- 17028888
TI - First evidence of poisonous shrews with an envenomation apparatus.
AB - Herein, we report evidence of an envenomation apparatus (EA) in two different
species of extinct "giant" shrews, Beremendia and an indeterminate soricine
(Mammalia, Eulipotyphla, Soricidae), documented by very well preserved fossil
specimens recovered from two Early Pleistocene cave deposits of the Sierra de
Atapuerca in Burgos, Spain. The two soricine taxa from Atapuerca have evolved
specialized teeth as EAs, which differ from those of recently reported mammals of
the Paleocene age, being more similar to the ones described in the modern
Solenodon. This discovery reveals the first instance of shrews possessing what
appears to be an EA, an evolutionary adaptation that, in these species, was
probably related to an increase in body mass and hunting of a larger-sized prey.
The Atapuerca specimens would have a highly specialized EA, one of the very few
reported for an extinct or living mammal of any time. In addition to the presence
of a gutter-like groove along the medial side of the crown of the lower incisors,
these two species also present stout jaws and a modified mandibular symphysis
with a conspicuous cavity, which in life would likely contain large amounts of
connective tissue. The strong mandible architecture of these large shrews would
be, in this way, reinforced by a more immovable symphysis, increasing the bite
force exerted over a potential prey. This adaptation, together with the grooved
incisors, would ensure a rapid and efficient transmission of the poisonous saliva
to paralyze relatively large-sized prey.
PMID- 17028889
TI - Concentrations of cortisol, testosterone and glycosylated haemoglobin (HbA1c)
among construction workers with 12-h workdays and extended workweeks.
AB - OBJECTIVES: Working on large scale construction sites have been shown to have
severe health consequences in terms of increased risk of hospitalization and
disability retirement compared to construction work in general. The aim of the
present study was to investigate whether large scale construction work involving
12-h workdays and extended workweeks leads to insufficient recovery measured as
increased catabolic and decreased anabolic metabolism. METHODS: The study group
comprised 40 male construction workers of which 21 had 12-h workdays and extended
workweeks (56 h/workweek). The comparison group consisted of 19 male construction
workers, who worked regular hours (37 h/week, weekends off). Measurements of
concentrations of cortisol in saliva and free testosterone and glycosylated
haemoglobin (HbA(1c)) in blood were made in a repeated measures design during 2
workweeks for both groups supplemented with 1 week off for construction workers
with extended workweeks. RESULTS: The diurnal profile of concentrations of
salivary cortisol for construction workers with extended workweeks differed from
the diurnal profile of salivary cortisol for those with regular work schedules (P
< 0.001). The construction workers with extended workweeks tended to have 15%
[95% CI -3%; 37%] higher concentrations of free testosterone in serum compared to
construction workers with regular work schedules (P = 0.09). There were no
differences between the two groups with respect to concentrations of HbA(1c).
There was no increasing trend in concentrations of cortisol or decreasing trend
in concentrations of testosterone during the extended workweek. The diurnal
profile for concentrations of cortisol differed between workdays and days off for
construction workers with extended workweeks (P = 0.003). CONCLUSION: In
conclusion, we observed no indications of insufficient recovery in terms of
increased catabolic or decreased anabolic metabolism in construction workers with
12-h workdays and extended workweeks compared to construction workers with
regular work schedules.
PMID- 17028890
TI - Clinical validity of the Japanese version of the Functional Assessment of Cancer
Therapy-Anemia Scale.
AB - GOALS OF WORK: The purpose of this study was to reveal the clinical validity of
the Japanese version of the Functional Assessment of Cancer Therapy-Anemia scale
(FACT-An) in relation to hemoglobin level. We also analyzed patients' scores for
the related FACT-General scale (FACT-G), the FACT Anemia subscale, and the FACT
Trial Outcome Index-Anemia scale (FACT TOI-An) to determine which was the most
sensitive to anemia measurements. MATERIALS AND METHODS: Throughout Japan, we
recruited 227 patients (mean+/-SD, 59+/-12.1 years old) diagnosed with a variety
of cancers. We correlated the severity of anemia, as measured by hemoglobin
levels, to scores on the FACT-An and on the other scales at baseline and at 3
months. MAIN RESULTS: The questionnaire completion rate was more than 98% at both
time points. The FACT-An had high internal consistency (Cronbach's alpha
coefficient >0.8). FACT-An scores were significantly and positively correlated
with hemoglobin levels both at baseline (r=0.24; 95% CI=0.12 to 0.36; n=225) and
at 3 months (r=0.24; 95% CI=0.10 to 0.36; n=204). FACT-G, FACT Anemia subscale,
and FACT TOI-An scores also successfully discriminated between patients with
lower (Hb <11.0 g/dl) and higher (Hb > or =11.0 g/dl) hemoglobin levels.
Moreover, the changes of these FACT scores over 3-months could discriminate
changes in hemoglobin level. CONCLUSION: The Japanese version of the FACT-An has
higher clinical validity and can be used to appropriately assess health-related
quality of life among Japanese cancer patients with anemia.
PMID- 17028891
TI - Temporal order judgment in dyslexia.
AB - Hari et al. (Brain 174:1373-1380, 2001) demonstrated that dyslexics showed a
sluggish attention capture in both visual hemifields. Additionally, they
indicated a left-right asymmetry in the perception of temporal order of two
visual stimuli (they performed worse than controls only if the stimulus in the
left hemifield preceded that in right hemifield). They suggested that a left
sided minineglect is associated with dyslexia. We hypothesized that if a kind of
neglect syndrome is responsible for the asymmetry they found, dyslexics should
not only show a left-right asymmetry in temporal order judgment of two laterally
presented stimuli but also perform equally well as controls when the stimuli are
vertically aligned. Our results indicated that in both tasks dyslexics performed
generally worse than normal readers. The results suggest that dyslexics suffer
from a more general problem of order discrimination.
PMID- 17028892
TI - Nucleus accumbens subregions: hodological and immunohistochemical study in the
domestic chick (Gallus domesticus).
AB - The nucleus accumbens was identified in avian species some time ago. However, the
precise localization and extent of this nucleus is still a matter of controversy.
We have used immunolabeling against calbindin, neuropeptide Y, and DARPP-32
(dopamine- and adenosine-related phosphoprotein, 32 kDa) for the selective
marking of putative accumbens subdivisions and have followed the anterograde
transport of biotinylated dextran amine injected to the nucleus tractus solitarii
region of 7-day-old domestic chicks. The nucleus accumbens extending between
rostrocaudal atlas coordinates A 10.6 and A 8.8 can be subdivided into the core
and shell, the core corresponding to the ventromedial and juxtaventricular medial
striatum laterodorsal to the bed nucleus of stria terminalis, and the shell
representing an arched region situated ventrally and ventrolaterally to the core.
Immunoreactivity to both calbindin and neuropeptide Y is more intense in the
shell than in the core division. DARPP-32 immunolabeling does not differ in the
two divisions but is markedly weaker in the bed nucleus of stria terminalis,
enabling the separation of this nucleus from the surrounding accumbens
subdivisions. Fibers from the nucleus solitarius predominantly terminate in the
shell division, similar to the situation described in mammals. Whereas the
suggested core lies entirely within the boundary of the medial striatum, the
shell seems partially to overlap the ventral pallidum. We have been unable to
subdivide the remaining part of accumbens lying rostral to A 10.6 into a putative
shell and core by the methods employed in the present study. This region probably
corresponds to the rostral pole of the nucleus accumbens.
PMID- 17028893
TI - Modulation of cell proliferation during palatogenesis by the interplay between
Tbx3 and Bmp4.
AB - During secondary palate development, two shelves are elevated to a horizontal
position above the tongue through a process involving many cellular mechanisms,
including proliferation. In particular, the expression patterns of Tbx3 and Bmp4,
which are colocalized at embryonic day 13.5 (E13.5) and have unique expression
patterns in specific regions at E14.5, have been investigated in early mouse
palatogenesis. Tbx3 expression is reported to be associated with Bmp4 signaling
during the process of organogenesis in other areas, such as limb development.
However, the function of Tbx3 and the relationship between Tbx3 and Bmp4 in
palate development have not been determined. We have examined the gene expression
pattern and cell proliferation in order to understand the mutual interactions and
function of Tbx3 and Bmp4. An electroporation method was used to investigate the
altered pattern of these genes after their over-expression in organ cultures.
NOGGIN protein-soaked beads were also implanted into the cultured palate to
determine the function of Bmp4 in palatogenesis. After electroporation and NOGGIN
bead implantation, the number of PCNA-positive cells was counted. The results
showed that Tbx3 and Bmp4 strongly up- and down-regulated each other in order to
control the proliferation of the palatal shelf. Thus, Tbx3 expression is induced
by Bmp4 in the mesenchyme of the anterior palatal shelves, whereas mesenchymal
expression of Tbx3 down-regulates Bmp4 expression in the mesenchyme of the
palate. The harmonization between Tbx3 and Bmp4 therefore controls cell
proliferation to regulate secondary palate development.
PMID- 17028894
TI - Molecular, cellular and histological changes in skin from a larval to an adult
phenotype during bony fish metamorphosis.
AB - Developmental models for skin exist in terrestrial and amphibious vertebrates but
there is a lack of information in aquatic vertebrates. We have analysed skin
epidermal development of a bony fish (teleost), the most successful group of
extant vertebrates. A specific epidermal type I keratin cDNA (hhKer1), which may
be a bony-fish-specific adaptation associated with the divergence of skin
development (scale formation) compared with other vertebrates, has been cloned
and characterized. The expression of hhKer1 and collagen 1alpha1 in skin taken
together with the presence or absence of keratin bundle-like structures have made
it possible to distinguish between larval and adult epidermal cells during skin
development. The use of a flatfish with a well-defined larval to juvenile
transition as a model of skin development has revealed that epidermal larval
basal cells differentiate directly to epidermal adult basal cells at the climax
of metamorphosis. Moreover, hhKer1 expression is downregulated at the climax of
metamorphosis and is inversely correlated with increasing thyroxin levels. We
suggest that, whereas early mechanisms of skin development between aquatic and
terrestrial vertebrates are conserved, later mechanisms diverge.
PMID- 17028895
TI - The clipped intestinal non-perforating anastomosis of small bowel: a new
technique.
AB - In contrast to adult surgery, the neonatal small intestine confronts the surgeon,
depending on the age of the patient, with variable diameters of the intestine.
Therefore, anastomoses are usually performed by hand with interrupted sutures. In
the presented study, a new technique is demonstrated. An anastomosis in the
distal ileum of Sprague Dawley rats was performed with a single clamp applicator
(Anastoclip). Small bowel anastomoses were performed in 32 rats. The clipped
bowel anastomosis was evaluated concerning stenosis, leakage, and adhesions in
comparison to the sutured anastomosis. Tension test and X-ray examination were
performed to measure the stability. The rats were sacrificed at day 3 or 14 after
laparotomy. The clipped anastomosis is feasible, and faster to perform than the
conventional hand-sutured anastomosis (Operation time: control group: 18.5 min
versus clipped group 4 min; p > 0.05). Furthermore, there were differences in the
mechanical stability, with higher tension forces needed for rupturing the clipped
anastomosis. There were fewer stenoses (16.5 mm stenotic diameter in the control
group versus 20.6 mm in the clipped group) and fewer adhesions in the group of
the clipped anastomosis. Histological examinations were performed and did not
show significant differences between the two groups. In the animal model
presented, the clipped, intestinal, non-perforating anastomosis (CINPA) shows
advantages compared to the common hand-sutured anastomosis.
PMID- 17028897
TI - Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical
outcomes in HLA-matched sibling allogeneic hematopoietic stem cell
transplantation.
AB - To evaluate whether the C677T and A1298C polymorphisms of 5,10
methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of
methotrexate (MTX) used in allogeneic stem cell transplantation, we performed
association analysis between these genetic polymorphisms and the clinical
outcomes of patients treated using human leukocyte antigen-matched sibling stem
cell transplantation. Patients (n=72) with hematological malignancy or aplastic
anemia were given a short course of MTX as a graft-versus-host disease
prophylaxis. Patients with the 677TT genotype showed higher total bilirubin
levels (677TT vs 677CT vs 677CC, 14.5 vs 8.6 vs 3.8 mg/dl, respectively; p=0.07)
and higher aspartic transaminase levels (677TT vs 677CT vs 677CC, 678.9 vs 156.6
vs 111.8 IU/l; p=0.04). Platelet recovery to 20,000/mul was slower for patients
with the 677TT genotype than for patients with other genotypes (677TT, 59 days;
677CT, 26 days; 677CC, 26 days; p=0.0075). The influences of the C677T
polymorphism on treatment-related mortality (TRM) were also analyzed. One-year
cumulative TRMs for patients with the TT genotype and the other genotypes were 66
and 30% (p=0.04) and their respective 1-year overall survivals were 30 and 56%
(p=0.11). No association was observed between the A1298C polymorphism and
clinical outcome for any of the different genotypes. Therefore, patients at high
risk of developing hepatic toxicity and with a poor likelihood of survival could
be selected by genotyping MTHFR C677T before allogeneic stem cell
transplantation.
PMID- 17028896
TI - Hematological malignancies in chronic inflammatory bowel diseases: report of five
cases and review of the literature.
AB - Several forms of primary and secondary hematological malignancies were rarely
observed during the clinical course of inflammatory bowel diseases (IBD).
Patients needing a prolonged treatment with immunosuppressants, such as
azathioprine or methotrexate, with familiarity and genetic predisposition seem to
be at a higher risk of leukemia. On the other hand, asthenia, thickness, and
fever may be the symptoms of the onset of each kind of hematological malignancy.
The finding of anemia, alteration of leukocyte count and large undetermined cells
may suggest increased probability of abnormal proliferation of a single white
blood cell line. In this report, the occurrence of hematological malignancies is
described in five patients affected by IBD (three with ulcerative colitis and two
with Crohn's disease) attending our Gastroenterology Unit.
PMID- 17028898
TI - Contrasting insulin dose-dependent defects in activation of atypical protein
kinase C and protein kinase B/Akt in muscles of obese diabetic humans.
AB - AIMS/HYPOTHESIS: Insulin-stimulated glucose transport in muscle is impaired in
obesity and type 2 diabetes, but alterations in levels of relevant signalling
factors, i.e. atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt),
are still uncertain. Clamp studies using maximal insulin concentrations have
revealed defects in activation of aPKC, but not PKB, in both obese non-diabetic
and obese diabetic subjects. In contrast, clamp studies using submaximal insulin
concentrations revealed defects in PKB activation/phosphorylation in obese non
diabetic and diabetic subjects, but changes in aPKC were not reported. The aim of
this study was to test the hypothesis that dose-related effects of insulin may
account for the reported differences in insulin signalling to PKB in diabetic
muscle. SUBJECTS AND METHODS: We compared enzymatic activation of aPKC and PKB,
and PKB phosphorylation (threonine-308 and serine-473) during hyperinsulinaemic
euglycaemic clamp studies using both submaximal (400-500 pmol/l) and maximal
(1400 pmol/l) insulin levels in non-diabetic control and obese diabetic subjects.
RESULTS: In lean control subjects, the submaximal insulin concentration increased
aPKC activity and glucose disposal to approximately 50% of the maximal level and
PKBbeta activity to 25% of the maximal level, but PKBalpha activity was not
increased. In these subjects, phosphorylation of PKBalpha and PKBbeta was
increased to near-maximal levels at submaximal insulin concentrations. In obese
diabetic subjects, whereas aPKC activation was defective at submaximal and
maximal insulin concentrations, PKBbeta activation and the phosphorylation of
PKBbeta and PKBalpha were defective at submaximal, but not maximal, insulin
concentrations. CONCLUSIONS/INTERPRETATIONS: Defective PKBbeta
activation/phosphorylation, seen on submaximal insulin stimulation in diabetic
muscle, may largely reflect impaired activation of insulin signalling factors
present in concentrations greater than those needed for full PKB
activation/phosphorylation. Defective aPKC activation, seen at all insulin
levels, appears to reflect, at least partly, an impaired action of distal factors
needed for aPKC activation, or poor aPKC responsiveness.
PMID- 17028899
TI - Increased intestinal permeability precedes clinical onset of type 1 diabetes.
AB - AIMS/HYPOTHESIS: Recent observations have shown subclinical intestinal
abnormalities in human type 1 diabetes. Whether these are related to the
pathogenetic process or secondary to the diabetes remains to be clarified. The
aim of this study was to investigate this issue by examining intestinal
permeability to sugars in subjects at different stages of type 1 diabetes:
preclinical, new-onset and long-term established disease. METHODS: Eighty-one
subjects with islet autoimmunity (18 preclinical, 28 new-onset and 35 long-term
type 1 diabetes) and 40 healthy control subjects were investigated by a lactulose
mannitol test, consisting of oral administration of the two sugars and
measurement of their urinary excretion. RESULTS: All groups of subjects with
islet autoimmunity showed an increase in intestinal permeability (p < or = 0.009
vs controls) to the disaccharide lactulose, indicative of a damaged barrier, but
a similar permeability to the monosaccharide mannitol (NS vs controls),
indicative of an integral surface mucosa; consequently there was an increase in
the lactulose:mannitol excretion ratio (p < or = 0.025 vs controls).
CONCLUSIONS/INTERPRETATION: These findings indicate the presence of a subclinical
enteropathy associated with type 1 diabetes that is already detectable before
clinical onset of the disease, and suggest that the small intestine is an organ
participating in the pathogenetic process of type 1 diabetes.
PMID- 17028900
TI - Langerhans cell histiocytosis.
AB - Langerhans cell histiocytosis (LCH) is a complex disease entity comprised of
three distinct clinical syndromes that demonstrate indistinguishable histology.
These syndromes are: eosinophilic granuloma, which is predominantly osseous or
pulmonary; Hand-Schuller-Christian's disease, which involves multiple organ
systems and, most typically, the skull base; and Letterer-Siwe's disease, the
most severe disease manifestation, which typically involves the abdominal
viscera. This article reviews our current understanding of Langerhans cell
histiocytosis by discussing the history, histology, etiology, and treatment of
the disease. It focuses on the radiographic findings and imaging modalities that
are the most useful in disease diagnosis and management.
PMID- 17028901
TI - Radiologic findings of the flexor pollicis longus hypoplasia.
AB - A case of a 10-year-old boy with hypoplasia of the flexor pollicis longus and
without other associated anomalies and trauma history is reported. Flexor
pollicis longus tendon anomalies are rare; several types of this congenital
anomaly have been reported in the literature. The diagnosis should be considered
to the conditions of a patient who was unable to flex the interphalangeal joint
of the thumb. Hypoplastic thumb or absent interphalangeal joint crease may be a
diagnostic feature in such cases. We preoperatively present the radiological
findings of this rare congenital anomaly. Ultrasound and magnetic resonance
imaging (MRI) features have never been reported in the literature.
PMID- 17028902
TI - A comparison of experimental designs for selection in breeding trials with nested
treatment structure.
AB - Plant breeders frequently evaluate large numbers of entries in field trials for
selection. Generally, the tested entries are related by pedigree. The simplest
case is a nested treatment structure, where entries fall into groups or families
such that entries within groups are more closely related than between groups. We
found that some plant breeders prefer to plant close relatives next to each other
in the field. This contrasts with common experimental designs such as the alpha
design, where entries are fully randomized. A third design option is to randomize
in such a way that entries of the same group are separated as much as possible.
The present paper compares these design options by simulation. Another important
consideration is the type of model used for analysis. Most of the common
experimental designs were optimized assuming that the model used for analysis has
fixed treatment effects. With many entries that are related by pedigree, analysis
based on a model with random treatment effects becomes a competitive alternative.
In simulations, we therefore study the properties of best linear unbiased
predictions (BLUP) of genetic effects based on a nested treatment structure under
these design options for a range of genetic parameters. It is concluded that BLUP
provides efficient estimates of genetic effects and that resolvable incomplete
block designs such as the alpha-design with restricted or unrestricted
randomization can be recommended.
PMID- 17028904
TI - A randomized comparison between intravaginal misoprostol and prostaglandin E2 for
labor induction.
AB - OBJECTIVE: The aim of this randomized study was to compare the effectiveness,
safety, and side effects of 6 h vaginal misoprostol versus vaginal prostaglandin
E(2) (PGE(2)) for labor induction. STUDY DESIGN: Fifty microgram of misoprostol
was given intravaginally in the misoprostol group (204 women), and 3 mg PGE(2)
was given intravaginally in the PGE(2) group (211 women). In both groups, the
dose was repeated every 6 h for a maximum of three doses, until active labor was
achieved. Artificial rupture of membranes and oxytocin infusion was used during
labor in both groups where it was indicated. RESULTS: The mean interval from the
institution of labor induction to delivery was 11.3 +/- 8.6 h for the misoprostol
group, and 15.7 +/- 9.3 h for PGE(2 )group (P < 0.05). In the misoprostol group,
oxytocin was used less frequently, but there was a higher prevalence of
tachysystole. No statistically significant differences were observed between the
two groups as regard abnormal patterns of fetal heart rate, the mode of delivery,
and the need for neonatal intervention. CONCLUSION: In conclusion, the
intravaginal administration of 50 mug misoprostol at 6 h interval (maximum three
doses) is comparable in safety, but more effective for induction of labor than 3
mg intravaginal PGE(2).
PMID- 17028905
TI - Evaluation of Eustachian tube function by sonotubometry: results and reliability
of 8 kHz signals in normal subjects.
AB - Sonotubometry allows an assessment of the Eustachian tube (ET) function under
physiological conditions. The reliability of the application of an 8 kHz pure
tone signal was investigated. In 40 normal subjects (80 ears) sonotubometric
studies were performed with a custom-made device. ET opening was provoked by
swallowing, yawning and Valsalva manoeuvre. An opening was detected in all
patients but not in all manoeuvres. Four characteristic sonotubogram types were
found. Most common was the spike-type (60%). The double-peak and the plateau
shaped curves occurred in 17% each. The finding of an descendant curve was rare
(5%). Of 623 measurements, only in 55% manouvres a positive sonotubometric result
was found despite the fact that the patients reported an opening in all cases.
The median opening time in dry swallowing, liquid swallowing, yawning and
Valsalva was found to be 486, 355, 1,263 and 1,250 ms. A median sound increase of
16.0, 13.8, 15.0 and 15.0 dB was recorded for these manoeuvres. There was a
statistic significant difference (P < 0.02) between the increase in sound
intensity of liquid and dry swallowing. There was also a statistic significant
difference found for the duration of the forced manoeuvres Valsalva and yawning
as compared to dry and liquid swallowing (P < 0.0001). The use of an 8 kHz pure
tone signal showed a limited sensitivity for the detection of ET openings. This
is mainly due to noise pollution, but also because of an altered positioning
and/or dislocation of the probes and compression of the nostrils. The application
of an 8 kHz signal is therefore not reliable enough for the use in practice.
Further technical refinements and the use of alternative signals are necessary
for a broader clinical application.
PMID- 17028906
TI - Relationship of DDX1 and NAG gene amplification/overexpression to the prognosis
of patients with MYCN-amplified neuroblastoma.
AB - PURPOSE: Amplification of the MYCN gene strongly correlates with advanced stage,
rapid tumor progression and poor prognosis in neuroblastoma (NB). Several genes
in the MYCN amplicon, including the DEAD box polypeptide 1 (DDX1) gene, and
neuroblastoma-amplified gene (NAG gene), have been found to be frequently co
amplified with MYCN in NB. The aim of this study was to clarify the prognostic
significance of the co-amplification or overexpression of DDX1 and NAG with MYCN.
PROCEDURE: The gene copy numbers and mRNA expression levels of MYCN, DDX1, and
NAG in 113 primary NBs were determined by the real-time quantitative polymerase
chain reaction or quantitative reverse transcriptase/polymerase chain reaction
assay. The relationships between gene co-amplification/overexpression status and
stage, age at diagnosis, and overall survival were analyzed. RESULTS: For
evaluating the frequency of DDX1 and NAG co-amplification, it proved appropriate
to discriminate NBs with <40 copies of MYCN amplification from those with > or
=40 copies of MYCN (DDX1, p = 0.00058; NAG, p = 0.0242, chi(2) for independence
test). In patients with MYCN-amplified NB aged > or =18 months, those with tumor
with enhanced DDX1 expression and low-NAG expression showed a significantly
better outcome than those with low-DDX1 expression or enhanced NAG expression (p
= 0.0245, log-rank test). None of the gene expression statuses had a significant
relation to disease stage or survival for patients <18 months old. No
relationship between any gene co-amplification status and disease stage, age at
diagnosis, or overall survival was found. CONCLUSIONS: Our findings suggest that
there may be a subset of NB in which enhanced DDX1 and low-NAG expression
consequent to DDX1 co-amplification without NAG amplification contributes to
susceptibility to intensive therapy. A larger study using an age cut-off of 18
months will be required.
PMID- 17028907
TI - Electro-encephalogram based brain-computer interface: improved performance by
mental practice and concentration skills.
AB - Mental imagination is the essential part of the most EEG-based communication
systems. Thus, the quality of mental rehearsal, the degree of imagined effort,
and mind controllability should have a major effect on the performance of electro
encephalogram (EEG) based brain-computer interface (BCI). It is now well
established that mental practice using motor imagery improves motor skills. The
effects of mental practice on motor skill learning are the result of practice on
central motor programming. According to this view, it seems logical that mental
practice should modify the neuronal activity in the primary sensorimotor areas
and consequently change the performance of EEG-based BCI. For developing a
practical BCI system, recognizing the resting state with eyes opened and the
imagined voluntary movement is important. For this purpose, the mind should be
able to focus on a single goal for a period of time, without deviation to another
context. In this work, we are going to examine the role of mental practice and
concentration skills on the EEG control during imaginative hand movements. The
results show that the mental practice and concentration can generally improve the
classification accuracy of the EEG patterns. It is found that mental training has
a significant effect on the classification accuracy over the primary motor cortex
and frontal area.
PMID- 17028908
TI - A comparison of nicotine dose estimates in smokers between filter analysis,
salivary cotinine, and urinary excretion of nicotine metabolites.
AB - RATIONALE: Nicotine uptake during smoking was estimated by either analyzing the
metabolites of nicotine in various body fluids or by analyzing filters from
smoked cigarettes. However, no comparison of the filter analysis method with body
fluid analysis methods has been published. OBJECTIVES: Correlate nicotine uptake
estimates between filter analysis, salivary cotinine, and urinary excretion of
selected nicotine metabolites to determine the suitability of these methods in
estimating nicotine absorption in smokers of filtered cigarettes. MATERIALS AND
METHODS: A 5-day clinical study was conducted with 74 smokers who smoked 1-19 mg
Federal Trade Commission tar cigarettes, using their own brands ad libitum.
Filters were analyzed to estimate the daily mouth exposure of nicotine. Twenty
four-hour urine samples were collected and analyzed for nicotine, cotinine, and
3'-hydroxycotinine plus their glucuronide conjugates. Saliva samples were
collected daily for cotinine analysis. RESULTS: Each method correlated
significantly (p < 0.01) with the other two. The best correlation was between the
mouth exposure of nicotine, as estimated by filter analysis, and urinary nicotine
plus metabolites. Multiple regression analysis implies that saliva cotinine and
urinary output are dependent on nicotine mouth exposure for multiple days.
Creatinine normalization of the urinary metabolites degrades the correlation with
mouth exposure. CONCLUSIONS: The filter analysis method was shown to correlate
with more traditional methods of estimating nicotine uptake. However, because
filter analysis is less complicated and intrusive, subjects can collect samples
easily and unsupervised. This should enable improvements in study compliance and
future study designs.
PMID- 17028909
TI - Initial experience with Lodox Statscan imaging system for detecting injuries of
the pelvis and appendicular skeleton.
AB - The purpose of this study is to assess detection of pelvic and extremity injuries
employing a rapid whole-body imaging system (Lodox Statscan). We retrospectively
reviewed 37 consecutive cases. The study was approved by our hospital review
board and carried out with Health Insurance Portability and Accountability Act
(HIPAA) compliance. Anterior-posterior (AP) whole-body Lodox Statscan (LS) exams,
obtained in 10-13 s, were reviewed by two musculoskeletal radiologists. Each
patient's concurrent computed radiographs (CR) and computed tomographic (CT)
studies were reviewed at a later date. There were 23 males and 14 females; ages
ranged from 14 to 103 years (average 40 years). Sixteen patients had a total of
73 abnormalities seen on LS, CR or CT. The LS examination identified 47
abnormalities (64.4%) in 15 patients. Twenty-six additional abnormalities were
detected with the other modalities (CR, CT) in 11 patients; 8 were evident on LS
images in retrospect, with the remaining 18 not identified even retrospectively.
Of these retrospectively occult injuries, only one was deemed significant to the
acute management of the patient. The LS imaging system seems to be a useful tool
for rapid screening of multitrauma patients.
PMID- 17028910
TI - Utilization of thick (>3 mm) maximum intensity projection images in coronary CTA
interpretation.
PMID- 17028911
TI - Teleradiology by resident education.
PMID- 17028912
TI - Effect of spatial frequency of stimulus on focal macular ERGs in monkeys :
fmacERG dependence on the spatial-frequency.
AB - PURPOSE: To determine the effect of the spatial frequency of a small grating
stimulus centered on the macula on the focal macular ERGs (fmacERGs) of monkeys.
METHODS: fmacERGs were recorded from eight eyes of four adult monkeys (Macaca
fuscata). The spatial frequency of the stimulus was changed from 0.25 to 8
cycles/degree. The luminance of the light bars was 10 cd/m(2), and the contrast
was 95%. The stimulus was flashed on and off with an on duration of 100 ms and an
off duration of 150 ms (4 Hz). The stimulus was centered on the fovea and
subtended 12.7 degrees at the cornea. The luminance of the steady light-adapting
background was 3.5 cd/m(2). The location of the stimulus on the retina was
monitored throughout the recordings. The effects of the spatial frequency of the
stimulus on the amplitudes and implicit times of the a-waves, b-waves, and
oscillatory potentials (OPs) were determined. fmacERGs were also recorded
following intravitreal tetrodotoxin (TTX). RESULTS: The amplitudes of the a- and
b-waves did not change with changes in the spatial frequency of the stimulus. The
OPs, on the other hand, responded best to the lowest spatial frequency, and the
OPs after the first two were attenuated at intermediate and higher frequencies
(Wilcoxon signed-rank test: P < 0.05). TTX reduced all OP wavelets in monkeys.
CONCLUSIONS: The OPs of the photopic macular ERGs are affected by the spatial
frequency of the stimulus and are reduced by TTX, consistent with their being
generated by inner retinal neurons.
PMID- 17028914
TI - Who are susceptible to pseudomembranous colitis among patients with presumed
antibiotic-associated diarrhea?
AB - PURPOSE: Pseudomembranous colitis is a severe form of antibiotic-associated
diarrhea. However, there have been no reports about the factors that make
patients with presumed antibiotic-associated diarrhea susceptible to
pseudomembranous colitis. This study was designed to determine the clinical risk
factors for pseudomembranous colitis among the patients with presumed antibiotic
associated diarrhea. METHODS: This was a retrospective study of 150 consecutive
patients admitted to our institution between January 2000 and December 2004 with
a diagnosis of presumed antibiotic-associated diarrhea. All patients underwent
sigmoidoscopy or colonoscopy because of diarrhea after administration of
antibiotics. Pseudomembranous colitis was confirmed both endoscopically and
histologically. Various clinical parameters were compared between the
pseudomembranous colitis group and non-pseudomembranous colitis group. RESULTS:
The mean age of patients was 61 years, and 60 percent (90/150) was female.
Pseudomembranous colitis was diagnosed in 53 percent (80/150). On univariate
analysis, older than aged 70 years (P = 0.014), antibiotic therapy for more than
15 days (P < 0.0001), hospital stay for more than 20 days (P < 0.0001), number of
antibiotics used more than one (P = 0.01), and surgical procedures (P = 0.029)
were significant parameters for pseudomembranous colitis. On multivariate
analysis, the important clinical risk factors were advanced age (older than aged
70 years; adjusted odds ratio, 2.7; 95 percent confidence interval, 1.208-6.131;
P < 0.016) and long hospital stay (more than 20 days; adjusted odds ratio, 5.1;
95 percent confidence interval, 2.1-12.259; P < 0.0001). When both risk factors
were present, the positive predictive value of pseudomembranous colitis was 0.86.
CONCLUSIONS: Advanced age and long hospital stay may make patients with presumed
antibiotic-associated diarrhea susceptible to pseudomembranous colitis.
Therefore, pseudomembranous colitis should be first suspected in cases with
presumed antibiotic-associated diarrhea having such risk factors.
PMID- 17028915
TI - Evaluation of a protocol-based management of rectal cancer.
AB - INTRODUCTION: The management of rectal cancer is multidisciplinary. We have
devised and implemented a standardized protocol. This study was designed to
evaluate the protocol and identify areas for improvement. METHODS: All patients
with a diagnosis of rectal cancer were staged preoperatively. Magnetic resonance
imaging and computed tomography were used to predict whether surgical resection
would be complete (RO) or involved (R1/2). Data were collected on preoperative
adjuvant therapy, surgical procedure, and subsequent pathologic stage, including
circumferential resection margin status. RESULTS: Between January 2000 and
October 2002, 163 patients were studied (107 male; median age, 70 (range, 60-77)
years). One hundred and fifty seven patients underwent surgical excision for
rectal cancer of whom 155 were discussed in the multidisciplinary meeting. One
hundred seventeen patients (75 percent) had pelvic magnetic resonance scan and
staging computed tomography of chest and abdomen, whereas 38 had computed
tomography only. Seventy-seven tumors were predicted as R0 and 78 as likely R1/2.
In the predicted RO group, 50 had surgery alone, 25 had short-course
radiotherapy, and 2 had chemoradiotherapy. Twelve patients (15.5 percent) had
involved circumferential resection margin on the histologic specimen. In the
predicted R1/2 group (n = 78), 40 patients received chemoradiotherapy, 11 had
short-course radiotherapy, and 27 had surgery alone. Thirty patients (38.4
percent) had involved circumferential resection margin. Circumferential margin
involvement was seen in 11 of 40 patients (27.5 percent) who received
chemoradiotherapy, 6 of 11 patients (54.5 percent) who received short-course
preoperative radiotherapy, and 13 of 27 patients (48.1 percent) who had surgery
alone. CONCLUSIONS: Protocol-driven management of rectal cancer within the
context of a multidisciplinary team has been demonstrated to work. Regular audit
allows for modification and improvement of the protocol as newer management
strategies evolve.
PMID- 17028916
TI - The impact of the allee effect in dispersal and patch-occupancy age on the
dynamics of metapopulations.
AB - In this paper, we introduce a Levins-type metapopulation model with empty and
occupied patches, and dispersing population. We structure the proportion of
occupied patches according to the patch-occupancy age. We observe that patch
occupancy age may destabilize the metapopulation, leading to persistent
oscillations. We also allow for the dispersal rate to vary with the proportion of
empty patches in a monotone or unimodal way. The unimodal dependence leads to
multiple non-trivial equilibria and bistability when the reproduction number of
the metapopulation R < 1 but greater than a lower critical value R(*). We show
that the metapopulation will persist independently of its initial status if R >
1.
PMID- 17028917
TI - Non-radioactive and colorimetric quantification of monocyte adhesion to
endothelial cells in early atherogenesis.
AB - Monocyte adhesion to vascular endothelium is an initial step in atherogenesis. To
quantify this, we incubated monocytes with cultured endothelial cells, and
quantified the adhered live monocytes using a colorimetric assay. Endothelium
activated with lipopolysaccharide attracted monocytes in a dose-dependent manner
and the adhesion was attenuated with post-treatments with L-ascorbic acid (53%),
alpha- (40%) and gamma-tocopherol (39%), resveratrol (39%), and Lithospermum
erythrorhizon root extract (45%). This non-radioactive, colorimetric assay may be
useful for screening anti-atherogenic compounds in early atherogenesis.
PMID- 17028918
TI - Development of an oxygen-rich biosensor using enzymatic reaction.
AB - This work reports a novel strategy for the development of an O2-rich biosensor.
The principle is based on an enzymatic reaction between catalase and H2O2 to
release O2, thus to increase the O2 amount in the enzyme matrix. This method
improves the determination reliability by alleviating the O2 dependence.
PMID- 17028919
TI - Ezrin mediates growth and survival in Ewing's sarcoma through the AKT/mTOR, but
not the MAPK, signaling pathway.
AB - Recent reports on the role of the membrane-cytoskeleton linker protein ezrin in
sarcomas showed an effect on the formation of metastases, dependent on the level
of ezrin expression. In this study, we explore the role of ezrin in Ewing's
sarcoma, a frequently fatal mesenchymal neoplasm of children and young adults.
Through both immunohistochemistry and Western immunoblot studies we find
ubiquitous, high-level expression of ezrin in Ewing's sarcoma. In contrast to the
observations in osteosarcoma and rhabdomyosarcoma, we demonstrate that inhibition
of ezrin-mediated signal transduction, through the expression of a non
phosphorylatable T567A mutant, slows primary growth of Ewing's sarcoma cells in
vitro. This reduction in growth is a result of increased apoptosis in the mutant
expressing cells. We further show that expression of this mutant reduces the
ability of Ewing's sarcoma cells to form experimental metastases in vivo.
Molecular examination reveals that the action of ezrin in Ewing's sarcoma is
dependent on the AKT/mTOR signal transduction cascade, but not MAP Kinase. These
results, therefore, demonstrate that, in Ewing's sarcoma, the biology of ezrin is
distinct from that described in other sarcomas. This study further validates
ezrin as a potential therapeutic target.
PMID- 17028920
TI - Diagnostic identification of malignant cells in the cerebrospinal fluid by tumor
specific qRT-PCR.
AB - Tumor specific quantitative RT-PCRs for two neuroblastoma specific molecular
markers, tyrosine hydroxylase (TH) and GD2 synthase, were used to unequivocally
demonstrate the neoplastic nature of the cells present in the cerebrospinal fluid
of a neuroblastoma patient. After radical surgery of two separate tumoral
lesions, localized in the extradural area, the patient presented with meningitis.
Common sites of neuroblastoma metastatization, e.g. bone and bone marrow, were
not infiltrated by tumor cells, as assessed by standard scintigraphy,
morphological investigation and by sensitive and specific immunocytochemical and
molecular assays. The results presented here demonstrate the successful use of
tumor-specific qRT-PCRs in cerebrospinal fluid to investigate questionable
clinical cases. The technique, which compared to other detection methods (e.g.,
immunocytochemistry) requires very few cells, yields unambiguous information once
a suspected diagnosis has been formulated and a tumor-specific molecular marker
is available.
PMID- 17028921
TI - Understanding metastatic SCCHN cells from unique genotypes to phenotypes with the
aid of an animal model and DNA microarray analysis.
AB - Metastasis of squamous cell carcinoma of the head and neck (SCCHN) is a
significant health-care problem worldwide. The 5-year survival rate is less than
50% for patients with lymph node metastases. Understanding the molecular basis of
SCCHN metastasis would facilitate the development of new therapeutic approaches
to the disease. To identify proteins that mediate SCCHN metastasis, we
established a SCCHN xenograft mouse model and performed in vivo selection from a
SCCHN cell line using the model. In the fourth round of in vivo selection,
significant incidences of metastases in lymph nodes (7/10) and lungs (6/10) were
achieved from a derived SCCHN cell line as compared with its parental cells, 1/5
in lymph nodes and 0/5 in lungs. Metastatic cell lines from lymph node metastases
and parental cell lines from non-metastatic xenograft tumors were subjected to
DNA microarray analysis using an Affymetrix gene chip HG-U133A, followed by data
mining studies. The identified metastasis-related genes were further evaluated
for their encoding protein products and the metastatic cells were examined by
biological analyses. DNA microarray analysis highlighted molecular features of
the metastatic SCCHN cells, including alteration of expression of cell-cell
adhesion proteins, epithelial cell markers, apoptosis and cell cycle regulatory
molecules. Further biological analyses of phenotypic alterations revealed that
the metastatic cells gained epithelial-mesenchymal transition (EMT) features and
were more resistant to anoikis, which are two of the important phenotypes for
metastatic SCCHN.
PMID- 17028922
TI - Expression of a metastatic phenotype in IFNs-primed/TNFalpha-activated B16 murine
melanoma cells: role of JAK1/PKCdelta signal transduction factors.
AB - In previous studies, we found that IFNgamma and TNFalpha generated by activated
macrophages stimulate the metastatic potential in F10-M3 cells, a clone isolated
from B16-F10 murine melanoma line. In this phenomenon, TNFalpha promoted the
expression of a metastatic phenotype in tumor cells previously primed with
IFNgamma. Here, we demonstrate that IFNalpha or IFNbeta may replace IFNgamma in
priming tumor cells. We also noticed that an enhancement of the expression of
p55TNFalpha receptor was associated with the preconditioning of tumor cells with
IFNgamma and IFNbeta. By the use of an appropriate inhibitor, we observed that
JAK1 signal transduction pathway was involved in the expression of a metastatic
phenotype and of p55TNFalpha receptor shown in IFNgamma- and IFNbeta-primed
melanoma cells stimulated with TNFalpha. Furthermore, the activity of the protein
kinase C (PKC) was required for IFNgamma-primed melanoma cells to express a
metastatic phenotype after stimulation with TNFalpha. In conclusion, our study
shows that a metastatic phenotype was expressed in B16 murine melanoma cells
stimulated with TNFalpha regardless of whether the cells were primed with
IFNgamma IFNalpha or IFNbeta. The molecular events leading to the expression of a
metastatic phenotype in F10-M3 melanoma cells are represented by: (a) an enhanced
expression of p55TNFalpha receptor in IFNs-primed tumor cells dependent on JAK1
signal transduction pathway; and (b) an intact PKC activity during TNFalpha
stimulation.
PMID- 17028923
TI - Soluble N-cadherin fragment promotes angiogenesis.
AB - Endothelial cells express two dependent intercellular adhesion molecules:
vascular endothelial (VE)-cadherin, specific for endothelial cells, and N
cadherin, also present in neuronal, lens, skeletal and heart muscle cells,
osteoblasts, pericytes and fibroblasts. While there exists a vast amount of
evidence that VE-cadherin promotes angiogenesis, the role of N-cadherin still
remains to be elucidated. We found that a soluble 90-kDa fragment N-cadherin
promotes angiogenesis in the rabbit cornea assay and in the chorioallantoic assay
when cleaved enzymatically from the extracellular domain of N-cadherin. Soluble N
cadherin stimulates migration of endothelial cells in the wound healing assay and
stimulates phosphorylation of extracellular regulated kinase. In vitro
experiments with PD173074 and knock-down of N-cadherin and fibroblast growth
factor (FGF)-receptor, showed that the pro-angiogenic effect of soluble N
cadherin is N-cadherin- and FGF-receptor-dependent. Our results suggest that
soluble N-cadherin stimulates migration of endothelial cells through the FGF
receptor.
PMID- 17028924
TI - Stem cell factor affects tumour progression markers in metastatic melanoma cells.
AB - Stem cell factor (SCF), next to various relevant biological effects exerted on
many cell types, is able to keep melanocyte homeostasis through its receptor c
kit. Only a minority of metastatic melanoma cells (MMC) express c-kit receptor,
but c-kit positive MMC move more slowly towards tumour progression and have a
more natural tendency to undergo apoptosis. In our study c-kit positive MMC from
human melanoma metastases and a c-kit positive human melanoma cell line-SK-MEL-28
showed a clear-cut reduction of cytokines normally up-regulated along melanoma
progression after SCF stimulation. SCF was also able to maintain all MMC and SK
MEL-28 cells in a well differentiated status with an increase in organellogenesis
and in particular of melanosomes in various degree of differentiation, but it did
not induce apoptosis as observed in other in vitro models. The increase of
melanosomes matched an increase of tyrosinase production. SCF did not modify the
expression of NOS while it enhanced the expression of HLA-DR molecules on MMC
membranes. Taken altogether these data stress the biological activity of SCF as a
cytokine which is able to maintain MMC in a well differentiated status, and
suggest a more in depth evaluation of possible effects of SCF on melanoma cells.
PMID- 17028925
TI - The inhibition of lung colonization of B16-F10 melanoma cells in EFA-deficient
animals is related to enhanced apoptosis and reduced angiogenesis.
AB - Previous studies conducted in our laboratory showed that the reproduction of
spontaneous and experimental metastases was reduced in host animals deprived of
essential fatty acids (EFA). In the present study, we have explored the
possibility whether apoptosis, proliferation, and angiogenesis might be involved
in the antimetastatic effect of EFA deficiency. To this aim, in pulmonary
colonies developed from B16-F10 cells in EFA-deficient animals or in animals fed
a 5% corn oil diet, we performed an immunohistochemical analysis of bcl-2/bax
proteins, PCNA, and VEGF and von Willebrand Factor (vWF), typical markers of
apoptosis, proliferation, and angiogenesis, respectively. Apoptosis was also
evaluated by detecting DNA fragments in metastatic cells. We found that the
reduction of pulmonary colonies grown in EFA-deficient animals was associated
with a high expression of apoptotic activity as revealed by the presence of
apoptotic nuclei and a high immunoreactivity for bax. Cell proliferation seemed
not to be influenced by EFA deficiency in view of the observation that PCNA was
highly expressed in pulmonary colonies of control as well as EFA-deficient
animals. Pulmonary colonies developed in EFA- deficient animals showed a lower
expression of VEGF and a decreased microvessel density, indicating that a reduced
angiogenesis contributes to the antimetastatic effects of EFA deficiency. Our
analysis of the results invokes the possibility that a relationship between
angiogenesis and apoptosis may account for the diminution of the development of
experimental metastases in the lungs of EFA-deficient animals.
PMID- 17028926
TI - Left ventricular outflow tract myxoma accompanied by dextrocardia with situs
inversus: a case report.
AB - Myxoma is the most frequently encountered primary tumour of the heart, comprising
more than 50% of all benign cardiac tumours. The case presented here was
diagnosed as having dextrocardia with situs inversus and concomitant left
ventricular outflow tract myxoma which has been very rarely encountered,
particularly consistent with the scarcity of reported cases.
PMID- 17028927
TI - Comprehensive evaluation of atrial septal defects in individuals undergoing
percutaneous repair by 64-detector row computed tomography.
AB - Transcatheter atrial septal defect closure is becoming more commonplace as it has
been demonstrated to be safe, efficacious and associated with low morbidity. Pre
procedural assessment of individuals has primarily relied upon transesophageal
echocardiography. We present four individuals who underwent both transesophageal
echocardiography as well as cardiac multidetector computed tomography. In all
four cases, multidetector computed tomography added incremental information above
the transesophageal echocardiogram. Multidetector computed tomography may play an
essential role in individuals with atrial septal defects undergoing percutaneous
transcatheter closure.
PMID- 17028928
TI - Multislice CT coronary angiography for the detection of burden, morphology and
distribution of atherosclerotic plaques in the left main bifurcation.
AB - The aim of the study was to explore the differences in plaque burden at different
segments of the left main bifurcation and its relationship with the bifurcation
angle using high-resolution multislice CT coronary angiography (MSCT). Patients
were evaluated using a 40-row MSCT scanner. One observer assessed the
localization, severity and distribution of plaques within the left main (LMCA)
bifurcation, whereas another observer defined the angle. Fifty patients were
included. The mean heart rate was 59.8 +/- 7.1. Seventeen (34%) patients
presented at least wall irregularities in the LMCA and in the ostial LCx, whereas
the ostial LAD was affected in 32 (64%) patients. More than 90% of plaques were
located opposite to the flow divider. The median bifurcation angle was 88.5
degrees (IQR 68.8 degrees, 101.4 degrees). Of the 18 patients with a normal
ostial LAD, 13 (72%) had a bifurcation angle < 88.5 degrees , whereas the 63% of
the patients with any LAD disease had an angle >or= 88.5 degrees (P = 0.018). In
conclusion, at the left main bifurcation, atherosclerotic plaques are commonly
located at the ostial LAD and opposite to the flow divider. The angle of the left
main bifurcation and the presence of plaques within the bifurcation are closely
related.
PMID- 17028929
TI - Kawasaki disease: role of coronary CT angiography.
AB - Invasive coronary angiography is considered to be the gold standard for diagnosis
and follow-up of coronary artery aneurysms, thrombosis and stenosis in patients
with Kawasaki Disease. However, the availability of multi-detector CT coronary
angiography provides a viable alternative as a non-invasive imaging modality for
sequential follow-up of patients with Kawasaki disease. High quality
multidetector CT angiography images of coronary arterial anatomy can be obtained
after adequate heart rate control using beta blockers.
PMID- 17028930
TI - An evolutionary heterogeneity model of late-life fecundity in Drosophila.
AB - There is now a significant body of research that establishes the deceleration of
mortality rates in late life and their ultimate leveling off on a late-life
plateau. Natural selection has been offered as one mechanism responsible for
these plateaus. The force of natural selection should also exert such effects on
female fecundity. We have already developed a model of female fecundity in late
life that incorporates the general predictions of the evolutionary model. The
original evolutionary model predicts a decline in fecundity from a peak in early
life, followed by a plateau with non-zero fecundity in late life. However, in
Drosophila there is also a well-defined decline in fecundity among dying flies,
here called the "death spiral". This effect produces heterogeneity between dying
and non-dying flies. Here a hybrid evolutionary heterogeneity model is developed
to accommodate both the evolutionary plateau prediction and the death spiral. It
is shown that this evolutionary heterogeneity model gives a much better fit to
late-life fecundity data.
PMID- 17028931
TI - Supplementation with a complex of active nutrients improved dermal and epidermal
characteristics in skin equivalents generated from fibroblasts from young or aged
donors.
AB - Cultured skin equivalent (SE, Mimeskin) was generated by co-culturing skin
fibroblasts and keratinocytes on a collagen-glycosaminoglycan-chitosan dermal
substrate. In order to examine donor age effect, fibroblasts from 19- (young) or
49- (aged) year-old females were used. Culture medium was supplemented with
nutrients complex containing soy extract, tomato extract, grape seed extract,
white tea extract, sodium ascorbate, tocopherol acetate, zinc gluconate and
BioMarine complex. Epidermal and dermal structure and composition were examined
after 42 and 60 days of culture. In untreated samples, SE generated from young
fibroblasts was superior to SE from aged fibroblasts in all characteristics.
Those include number and regularity of keratinocyte layers, number of
keratinocytes expressing proliferation marker Ki67, content of collagen type I,
fibrillin-1, elastin, and SE lifespan. Effects of nutritional supplementation
were observed in SE from both young and aged fibroblasts, however, those effects
were more pronounced in SE from aged fibroblasts. In epidermis, the treatment
increased number of keratinocyte layers and delayed epidermal senescence. The
number of cells expressing Ki67 was nine folds higher than those of controls, and
was similar to that of young cell SE. In dermis, the treatment increased mRNA
synthesis of collagen I, fibrillin-1 and elastin. In conclusion, skin cell donor
age had major important effect on formation of reconstructed SE. Imperfections in
epidermal and dermal structure and composition as well as life span in SE from
aged cells can be improved by supplementation with active nutrients.
PMID- 17028932
TI - Oxidative stress and brain aging: is zinc the link?
AB - Zn(2+) dyshomeostasis has been strongly linked to neuronal injury in many
neurological conditions. Toxic accumulation of intracellular free Zn(2+)
([Zn(2+)](i)) may result from either flux of the cation through glutamate
receptor-associated channels, voltage-sensitive calcium channels, or Zn(2+)
sensitive membrane transporters. Injurious [Zn(2+)](i) rises can also result from
release of the cation from intracellular sites such as metallothioneins (MTs) and
mitochondria. Chronic inflammation and oxidative stress are hallmarks of aging.
Zn(2+) homeostasis is affected by oxidative stress, which is a potent trigger for
detrimental Zn(2+) release from MTs. Interestingly, Zn(2+) itself is a strong
inducer of oxidative stress by promoting mitochondrial and extra-mitochondrial
production of reactive oxygen species. In this review, we examine how Zn(2+)
dyshomeostasis and oxidative stress might act synergistically to promote aging
related neurodegeneration.
PMID- 17028933
TI - Effect of zinc ions on apoptosis in PBMCs from healthy aged subjects.
AB - Immunosenescence features, such as thymic involution, alteration of T-cell
repertoire, autoimmunity and accumulation of memory/effector T cells, may be the
result, at least in part, of a zinc deficiency, which is often observed during
ageing. Zinc, as essential trace element, affects the immune system function and
it is an important regulator of apoptosis of immune cells. In this study we
addressed the question whether zinc supplementation in vitro at physiological
doses can affect spontaneous and oxidative stress-induced apoptosis in peripheral
blood mononuclear cells from subjects of three different age groups: young (mean
age 28 years), old (mean age 72 years) and nonagenarians. We studied different
parameters related to apoptosis (phosphatydilserine exposure, mitochondrial
membrane potential, caspase 3 cleavage) and we found that zinc, while decreasing
spontaneous apoptosis, can increase oxidative stress-induced apoptosis in an age
related fashion, being this effect more evident in nonagenarians than in old or
young subjects. In particular, zinc can increase late apoptosis/necrosis, a
phenomenon that could trigger unnecessary inflammation in vivo. We surmise that
these age-associated alterations in susceptibility to apoptosis may be due to a
different effect of zinc on T cell subsets, that are altered in very old people,
and finally that the zinc deficiency, which is often observed in aged subjects,
could be a compensatory mechanism to counteract the inflammatory status of the
elderly.
PMID- 17028934
TI - Bacterial endosymbioses in Solemya (Mollusca: Bivalvia)--model systems for
studies of symbiont-host adaptation.
AB - Endosymbioses between chemosynthetic bacteria and marine invertebrates are
remarkable biological adaptations to life in sulfide-rich environments. In these
mutualistic associations, sulfur-oxidizing chemoautotrophic bacteria living
directly within host cells both aid in the detoxification of toxic sulfide and
fix carbon to support the metabolic needs of the host. Though best described for
deep-sea vents and cold seeps, these symbioses are ubiquitous in shallow-water
reducing environments. Indeed, considerable insight into sulfur-oxidizing
endosymbioses in general comes from detailed studies of shallow-water protobranch
clams in the genus Solemya. This review highlights the impressive body of work
characterizing bacterial symbiosis in Solemya species, all of which are presumed
to harbor endosymbionts. In particular, studies of the coastal Atlantic species
Solemya velum and its larger Pacific congener Solemya reidi are the foundation
for our understanding of the metabolism and physiology of marine bivalve
symbioses, which are now known to occur in five families. Solemya velum, in
particular, is an excellent model organism for symbiosis research. This clam can
be collected easily from coastal eelgrass beds and maintained in laboratory
aquaria for extended periods. In addition, the genome of the S. velum symbiont is
currently being sequenced. The integration of genomic data with additional
experimental analyses will help reveal the molecular basis of the symbiont-host
interaction in Solemya, thereby complementing the wide array of research programs
aimed at better understanding the diverse relationships between bacterial and
eukaryotic cells.
PMID- 17028935
TI - Karyotypic relationships among the tribes of Hypostominae (Siluriformes:
Loricariidae) with description of XO sex chromosome system in a Neotropical fish
species.
AB - The family Loricariidae, with about 683 species, is one the largest fish families
in the world. The subfamily Hypostominae was recently reviewed and is now divided
in five tribes. With the main objective of contributing to a better understanding
of the relationships of the members of the subfamily Hypostominae, cytogenetic
analyses were conducted in seven species (three Hypostomini, three
Pterygoplichthini and two Ancistrini) from Brazil and Venezuela. In
Pterygoplichthini, all species show 2n = 52 chromosomes. In Hypostomini
Hypostomus ancistroides has 2n = 68, H. regani 2n = 72 and Hypostomus goyazensis
2n = 72 chromosomes. In Ancistrini Ancistrus n. sp. 1 has 2n = 39/40 with a sex
chromosome system of the type XX/X0, which is a novelty for neotropical fishes,
and Ancistrus n. sp. 2 has 2n = 52 chromosomes. Six species have single Ag-NORs
and two multiple Ag-NORs. The possible cytogenetic relationships among the
species of Hypostominae are discussed.
PMID- 17028936
TI - Direct determination of the influence of extreme temperature on transposition and
structural mutation rates of Drosophila melanogaster mobile elements.
AB - Two sets of mutation accumulation lines, one reared at 28 degrees C and the other
at 24 degrees C, were compared for their transposition and rearrangement rates of
eleven transposable element families. The changes affecting mobile elements were
analysed by the Southern technique and in situ hybridization. No differences were
found between treated and control lines. The role of the host genotype in
transposition control and the significance of structural mutations in
transposable element dynamics are discussed.
PMID- 17028937
TI - Diversity of endogenous small non-coding RNAs in Oryza sativa.
AB - Small non-coding RNAs play important roles in regulating cell functions by
controlling mRNA turnover and translational repression in eukaryotic cells. Here
we isolated 162 endogenous small RNA molecules from Oryza sativa, which ranged
from 16 to 35 nt in length. Further analysis indicated that they represented a
diversity of small RNA molecules, including 17 microRNAs (miRNAs), 30 tiny non
coding RNAs (tncRNAs) and 20 repeat-associated small interfering RNAs (rasiRNAs).
Among 17 miRNAs, 13 were novel miRNA candidates and their potential targets were
important regulatory genes in the rice genome. We also found that a cluster of
small RNAs, including many rasiRNAs, matched to a nuclear DNA fragment that
evolutionarily derived from chloroplast. These results demonstrate clearly the
existence of distinct types of small RNAs in rice and further suggest that small
RNAs may control gene regulation through diverse mechanisms.
PMID- 17028938
TI - Chromosomes of three freshwater stingrays (Rajiformes Potamotrygonidae) from the
Rio Negro basin, Amazon, Brazil.
AB - Potamotrygonidae is the representative family of South American freshwater
elasmobranchs. It is a monophyletic group containing 20 species grouped into
three genera. Three species belonging to two genera of this family were collected
from the middle Negro River, Amazonas, Brazil, and studied cytogenetically:
Paratrygon aiereba, Potamotrygon motoro and Potamotrygon orbignyi. Paratrygon
aiereba presented 2n = 90 chromosomes and 4M+2SM+10ST+74A. Both species of
Potamotrygon presented 2n = 66 chromosomes and differed in their chromosomal
formulas: P. motoro had 18M+12SM+10ST+26A and P. orbignyi had 22M+10SM+8ST+26A.
No sex heteromorphism was detected. The Fundamental Number (FN) was 106 for the
three species. A system of multiple NORs was found in the three species, but with
interspecific differences in terms of location and position of the active Ag-NORs
sites. Paratrygon aiereba presented only four sites on the short arms of two
chromosomal pairs, both in terminal regions. Potamotrygon motoro presented seven
sites, on the long and short arms, all in terminal regions of non-homologous
chromosomes; P. orbignyi presented eight sites on the long arms, all in terminal
regions, of non-homologous chromosomes. The constitutive heterochromatin was in
pericentromeric regions of all chromosomes, and no significant interspecific
difference was found in relation to this marker.
PMID- 17028939
TI - Genetic spatial clustering: significant implications for conservation of wild
soybean (Glycine soja: Fabaceae).
AB - Knowledge of spatial patterns of genetic variation within populations of wild
relative species has significant implications with respect to sampling strategies
for ex situ and in situ conservation. To study spatial genetic structure of wild
soybean (Glycine soja Sieb. et Zucc.) at the fine scale, three natural
populations in northern China were analyzed using inter-simple sequence repeat
(ISSR) fingerprints for estimating kinship coefficients. A regression analysis of
kinship coefficients against spatial distances revealed that individuals
occurring close together tended to be more genetically related. The Sp statistic
further indicated a comparable spatial pattern among the three wild soybean
populations with similar Sp values (mean = 0.0734, varied from 0.0645 to 0.0943)
detected across the three populations. Genetic patches were on average ca. 20 m
in size, and the effective neighborhood sizes varied between 10 and 15 m. The
spatial genetic structure evident in the wild soybean populations may be
attributed to the restricted seed dispersal and predominant inbreeding mating
system of this species. The detection of family structure in the populations of
wild soybean has a significant implication for the effective conservation of the
important genetic resources.
PMID- 17028940
TI - Spatial variation in colour morph, spotting and allozyme frequencies in the candy
stripe spider, Enoplognatha ovata (Theridiidae) on two Swedish archipelagos.
AB - The selective significance, if any, of many invertebrate visible polymorphisms is
still not fully understood. Here we examine colour- and black spotting-morph
frequencies in the spider Enoplognatha ovata in populations on two Swedish
archipelagos with respect to different spatial scales and, in one archipelago,
against the background of variation at four putative neutral allozyme marker
loci. Every population studied was polymorphic for colour and 28 out of 30
contained all three colour morphs--lineata, redimita and ovata. We found no
evidence for a breakdown in the traditional colour morph designation previously
suggested for other northern European populations of this species. For colour
there is no significant heterogeneity at spatial scales greater than between
local populations within islands. Black spotting frequencies show a similar lack
of pattern over larger spatial scales except that there are significant
differences between the Stockholm and Goteborg archipelagos. Measures of
population differentiation (theta) within the Stockholm islands for the two
visible systems show them to be significantly more differentiated than the
neutral markers, suggesting local selection acting on them in a population
specific manner. On the basis of previous observations and the distribution of
spotting phenotypes on a European scale, it is argued that thermal selection
might operate on black spotting during the juvenile stages favouring more spots
in continental climates. It is not clear what selective forces act on colour.
PMID- 17028941
TI - Mapping of SMV resistance gene Rsc-7 by SSR markers in soybean.
AB - Soybean mosaic virus (SMV) is one of the most prevalent pathogens that limit
soybean production. In this study, segregation ratios of resistant plants to
susceptible plants in P1, P2, F1, F2 populations of Kefeng No. 1 (P1) x Nannong
1138-2 (P2) and derived RIL populations, were used to study the inheritance of
resistance to the SMV strain SC-7. Populations Kefeng No. 1 and F1 were found to
be completely resistant to this SMV strain while Nannong 1138-2 was susceptible
to it. The F2 and RIL populations segregated to fit a ratio of 3:1 and 1:1for
resistant plants to susceptible ones, respectively. These results indicated that
a single dominant gene, designated as Rsc-7, controlled resistance to the SMV
strain SC-7 in Kefeng No.1. SSR markers were used to analyze the RIL population
and MAPMAKER/EXP 3.0b was employed to establish linkage between markers and this
resistance gene. Combining the data of SSRs and resistance identification, a
soybean genetic map was constructed. This map, covering 2625.9 cM of the genome,
converged into 24 linkage groups, consisted of 221 SSR markers and the resistance
gene Rsc-7. The Rsc-7 gene was mapped to the molecular linkage group G8-D1b+W.
SSR markers Satt266, Satt634, Satt558, Satt157, and Satt698 were found linked to
Rsc-7 with distances of 43.7, 18.1, 26.6, 36.4 and 37.9 cM, respectively.
PMID- 17028942
TI - Altitudinal patterns for longevity, fecundity and senescence in Drosophila
buzzatii.
AB - We tested for variation in longevity, senescence rate and early fecundity of
Drosophila buzzatii along an elevational transect in Argentina, using laboratory
reared flies in laboratory tests performed to avoid extrinsic mortality. At 25
degrees C, females from lowland populations lived longer and had a lower
demographic rate of senescence than females from highland populations. Minimal
instead of maximal temperature at the sites of origin of population best
predicted this cline. A very different pattern was found at higher test
temperature. At 29.5 degrees C, longevity of males increased with altitude of
origin of population. No clinal trend was apparent for longevity of females at
29.5 degrees C. There was evidence for a trade-off between early fecundity and
longevity at non-stressful temperature (25 degrees C) along the altitudinal
gradient. This trait association is consistent with evolutionary theories of
aging. Population-by-temperature and sex-by-temperature interactions indicate
that senescence patterns are expressed in environment specific ways.
PMID- 17028943
TI - Accelerated molecular evolution in Microtus (Rodentia) as assessed via complete
mitochondrial genome sequences.
AB - Microtus is one of the most taxonomically diverse mammalian genera, including
over 60 extant species. These rodents have evolved rapidly, as the genus
originated less than 2 million years ago. If these numbers are taken at face
value, then an average of 30 microtine speciation events have occurred every
million years. One explanation for the rapid rate of cladogenesis in Microtus
could be the karyotypic differentiation exhibited across the genus: diploid
numbers range from 17 to 64. Despite the striking chromosomal variability within
Microtus, phenotypic variation is unremarkable. To determine whether nucleotide
substitution rates are also elevated in voles, we sequenced the entire
mitochondrial DNA (mtDNA) genome of the Eurasian sibling vole (Microtus
rossiaemeridionalis). We compared this genome to another previously sequenced
vole mtDNA genome (Microtus kikuchii) and performed pairwise sequence comparisons
with the mtDNA genomes of ten additional mammalian genera. We found that
microtine mtDNA genomes are evolving more rapidly than any other mammalian
lineage we sampled, as gauged by the rate of nucleotide substitution across the
entire mtDNA genome as well as at each individual protein-coding gene.
Additionally, we compared substitution rates within the cytochrome b gene to
seven other rodent genera and found that Microtus mtDNA is evolving fastest. The
root cause of accelerated evolution in Microtus remains uncertain, but merits
further investigation.
PMID- 17028944
TI - Sexual dimorphism of body size and sternopleural bristle number: a comparison of
geographic populations of an invasive cosmopolitan drosophilid.
AB - Zaprionus indianus is a cosmopolitan drosophilid, of Afrotropical origin, which
has recently colonized South America. The sexual dimorphism (SD) of body size is
low, males being almost as big as females. We investigated 10 natural
populations, 5 from America and 5 from Africa, using the isofemale line
technique. Three traits were measured on each fly: wing and thorax length and
sternopleural bristle number. Two indices of SD were compared, and found to be
highly correlated (r > 0.99). For the sake of simplicity, only the female/male
(F/M) ratio was further considered. A significant genetic variability of SD was
found in all cases, although with a low heritability (intra-class correlation of
0.13), about half the value found for the traits themselves. For size SD, we did
not find any variation among continents or any latitudinal trend, and average
values were 1.02 for wing length and 1.01 for thorax length. Bristle number SD
was much greater (1.07). Among mass laboratory strains, SD was genetically much
more variable than in recently collected populations, a likely consequence of
laboratory drift. Altogether, SD, although genetically variable and prone to
laboratory drift, is independent of size variations and presumably submitted to a
stabilizing selection in nature.
PMID- 17028945
TI - Non-concerted evolution of the RET76 satellite DNA family in Reticulitermes taxa
(Insecta, Isoptera).
AB - The evolutionary dynamics of satellite DNA is most often studied in canonical
mating systems, where bisexuality and panmixis are the rule. In eusocial
termites, the limited number of reproducers starting a new colony and the
maintenance of the colony through few neotenics act as bottle-necks both in space
and time. No data on repetitive DNA are available for Isoptera and for their
peculiar reproductive strategy. Here we present the first satellite DNA family
isolated in European Reticulitermes. RET76 is a G+C rich satellite embodying two
sub-families with a 76 bp monomer. RET76 sequences are highly variable (sequence
homology is lower than 80% within sub-families and lower than 68% in the entire
family) and this variability is equally distributed among the eight analysed
taxa, thus depicting a pattern of non-concerted evolution. The absence of variant
fixation--together with the strict monomer length conservation--may be explained
at the molecular level as due to functional constraints acting on these
sequences, and/or at the organismic level by considering the involvement of
eusociality in preventing or greatly reducing variant fixation, somehow mimicking
an unisexual strategy.
PMID- 17028946
TI - Box-Cox transformation for QTL mapping.
AB - The maximum likelihood method of QTL mapping assumes that the phenotypic values
of a quantitative trait follow a normal distribution. If the assumption is
violated, some forms of transformation should be taken to make the assumption
approximately true. The Box-Cox transformation is a general transformation method
which can be applied to many different types of data. The flexibility of the Box
Cox transformation is due to a variable, called transformation factor, appearing
in the Box-Cox formula. We developed a maximum likelihood method that treats the
transformation factor as an unknown parameter, which is estimated from the data
simultaneously along with the QTL parameters. The method makes an objective
choice of data transformation and thus can be applied to QTL analysis for many
different types of data. Simulation studies show that (1) Box-Cox transformation
can substantially increase the power of QTL detection; (2) Box-Cox transformation
can replace some specialized transformation methods that are commonly used in QTL
mapping; and (3) applying the Box-Cox transformation to data already normally
distributed does not harm the result.
PMID- 17028947
TI - Origin and evolution of the Amyrel gene in the alpha-amylase multigene family of
Diptera.
AB - Alpha-amylase genes often form multigene families in living organisms. In
Diptera, a remote paralog, Amyrel, had been discovered in Drosophila, where this
gene is currently used as a population and phylogenetic marker. The putative
encoded protein has about 40% divergence with the classical amylases. We have
searched the presence of the paralog in other families of Diptera to track its
origin and understand its evolution. Amyrel was detected in a number of families
of Muscomorpha (Brachycera-Cyclorrapha), suggesting an origin much older than
previously thought. It has not been found elsewhere to date, and it is absent
from the Anopheles gambiae genome. The intron-exon structures of the genes found
so far suggest that the ancestral gene (before the duplication which gave rise to
Amyrel) had two introns, and that subsequent, repeated and independent loss of
one or both introns occurred in some Muscomorpha families. It seems that the
Amyrel protein has experienced specific amino acid substitutions in regions
generally well conserved in amylases, raising the possibility of peculiar,
functional adaptations of this protein.
PMID- 17028948
TI - Constitutive heterochromatin, 5S and 18S rDNA genes in Apareiodon sp.
(Characiformes, Parodontidae) with a ZZ/ZW sex chromosome system.
AB - Karyotype, sex chromosome system and cytogenetics characteristics of an
unidentified species of the genus Apareiodon originating from Piquiri River
(Parana State, Brazil) were investigated using differential staining techniques
(C-banding and Ag-staining) and fluorescent in situ hybridization (FISH) with 5S
and 18S rDNA probes. The diploid chromosome number was 2n = 54 with 25 pairs of
meta- (m) to submetacentric (sm) and 2 pairs of subtelocentric (st) chromosomes.
The major ribosomal rDNA sites as revealed by Ag-staining and FISH with 18S rDNA
probe were found in distal region of longer arm of st chromosome pair 26, while
minor 5S sites were observed in the interstitial sites on chromosome pairs 2
(smaller cluster) and 7 (larger one). The C-positive heterochromatin had
pericentromeric and telomeric distribution. The heteromorphic sex chromosome
system consisted of male ZZ (pair 21) and female middle-sized m/st Z/W
chromosomes. The pericentric inversion of heterochromatinized short arm of
ancestral Z followed by multiplication of heterochromatin segments is
hypothesized for origin of W chromosome. The observed karyotype and chromosomal
markers corresponded to those found in other species of the genus.
PMID- 17028949
TI - Accumulation of chloroplast DNA sequences on the Y chromosome of Silene
latifolia.
AB - Silene latifolia is a model dioecious plant with heteromorphic sex chromosomes.
The Y chromosome is the largest in this species. Theoretical models propose an
accumulation of repetitive DNA sequences in non-recombining parts of the Y
chromosome. In this study, we isolated a BAC7H5 clone preferentially hybridizing
to the Y chromosome of S. latifolia. Sequence analysis revealed that this BAC7H5
contains part of the chloroplast genome, indicating that these chloroplast
sequences have accumulated on the Y chromosome and also may contribute to its
large size. We constructed Y chromosome- and X chromosome-specific libraries and
screened them to find Y- and/or X-linked copies of chloroplast sequences.
Sequence analysis revealed higher divergence of a non-genic region of the
chloroplast sequences located on the Y chromosome while genic regions tested
showed only very low (max 0.9%) divergence from their chloroplast homologues.
PMID- 17028950
TI - Molecular phylogeny of black flies (Diptera: Simuliidae) from Thailand, using
ITS2 rDNA.
AB - The sequences of the second internal transcribed spacer (ITS2) of ribosomal DNA
(rDNA) were determined for 40 black fly species from Thailand, belonging to 4
subgenera of the genus Simulium, namely Gomphostilbia (12 species), Nevermannia
(5 species), Montisimulium (1 species), Simulium sensu stricto (21 species), and
an unknown subgenus with one species (Simulium baimaii). The length of the ITS2
ranged from 247 to 308 bp. All black fly species had high AT content, ranging
from 71 to 83.8%. Intraindividual variation (clonal variation) occurred in 13
species, ranging from 0.3 to 1.1%. Large intrapopulation and interpopulation
heterogeneities exist in S. feuerboni from the same and different locations in
Doi Inthanon National Park, northern Thailand. Phylogenetic relationships among
40 black fly species were examined using PAUP (version 4.0b10) and MrBAYS
(version 3.0B4). The topology of the trees revealed two major monophyletic
clades. The subgenus Simulium and Simulium baimaii were placed in the first
monophyletic clade, whereas the subgenera Nevermannia + Montisimulium were placed
as the sister group to the subgenus Gomphostilbia in the second monophyletic
clade. Our results suggest that S. baimaii belongs to the malyschevi-group or
variegatum-group in the subgenus Simulium. The molecular phylogeny generally
agrees with existing morphology-based phylogenies.
PMID- 17028951
TI - Tuareg, a novel miniature-inverted repeat family of pearl millet (Pennisetum
glaucum) related to the PIF superfamily of maize.
AB - Miniature-inverted repeat transposable elements (MITEs) are abundantly repeated
in plant genomes and are especially found in genic regions where they could
contribute regulatory elements for gene expression. We describe with molecular
and cytological tools the first MITE family reported in pearl millet: Tuareg. It
was initially detected in the pearl millet ortholog of Teosinte-branched1, an
important developmental gene involved in the domestication of maize. The Tuareg
family was amplified recently in the pearl millet genome and elements were found
more abundant in wild than in domesticated plants. We found that they shared
similarity in their terminal repeats with the previously described mPIF MITEs and
that they are also present in other Pennisetum species, in maize and more
distantly related grasses. The Tuareg family may be part of MITEs activated by
PIF-like transposases and it could have been mobile since pearl millet
domestication.
PMID- 17028952
TI - Direct and correlated effects of selection on flight after exposure to thermal
stress in Drosophila melanogaster.
AB - To demonstrate how insects may adapt to ecologically relevant levels of heat
stress, we performed artificial selection on the ability of Drosophila
melanogaster to fly after an exposure to a high but non-lethal thermal stress.
Both tolerance and intolerance to heat stress arose very quickly, as only a few
generations of selection were necessary to cause significant separation between
high and low lines for heat tolerance. Estimates of heritability based on the
lines artificially selected for increased flight ability ranged from 0.024 to
0.052, while estimates of heritability based on the lines selected for the
inability to fly after heat stress varied between 0.035 and 0.091. Reciprocal F1
crosses among these lines revealed strong additive effects of one or more
autosomes and a weaker X-chromosome effect. This variation apparently affected
flight specifically; neither survival to a more extreme stress nor knockdown by
high temperature changed between lines selected for high and low heat tolerance
as measured by flight ability. As the well-studied heat-shock response is
associated with heat tolerance as measured by survival and knockdown, the aspects
of the stress physiology that actually affect flight ability remains unknown.
PMID- 17028953
TI - Genetic variation in two land snails, Cepaea nemoralis and Succinea putris
(Gastropoda, Pulmonata), from sites differing in heavy metal content.
AB - Allozyme variation was determined in two land snail species (Cepaea nemoralis and
Succinea putris) from four localities in northern Belgium. In each locality we
selected a polluted and a nearby, less-polluted, reference plot. We examined
whether (i) genetic variability differed between the polluted and reference
plots, (ii) populations from polluted plots experienced recent bottlenecks, and
(iii) certain allele or genotype frequencies were associated with the pollution.
Our results suggest that (i) about 13% of the genetic differentiation in C.
nemoralis and 5% in S. putris was due to differences among polluted and reference
plots, (ii) polluted and reference plots had comparable levels of genetic
variation, but in C. nemoralis observed heterozygosities were higher in polluted
plots, (iii) most plots showed significant evidence for recent bottlenecks,
irrespective of the degree of pollution, so that bottlenecks seem poor indicators
of pollution-induced stress in land snails, and (iv) mutagenic or pollution
induced modifications did not seem to account for new allozyme variants in
polluted sites. The observed patterns of genetic variation may be explained by
the action of genetic drift, pollution-mediated selection, restricted gene flow,
or a combination of these processes.
PMID- 17028954
TI - FISH on avian lampbrush chromosomes produces higher resolution gene mapping.
AB - Giant lampbrush chromosomes, which are characteristic of the diplotene stage of
prophase I during avian oogenesis, represent a very promising system for precise
physical gene mapping. We applied 35 chicken BAC and 4 PAC clones to both mitotic
metaphase chromosomes and meiotic lampbrush chromosomes of chicken (Gallus gallus
domesticus) and Japanese quail (Coturnix coturnix japonica). Fluorescence in situ
hybridization (FISH) mapping on lampbrush chromosomes allowed us to distinguish
closely located probes and revealed gene order more precisely. Our data extended
the data earlier obtained using FISH to chicken and quail metaphase chromosomes 1
6 and Z. Extremely low levels of inter- and intra-chromosomal rearrangements in
the chicken and Japanese quail were demonstrated again. Moreover, we did not
confirm the presence of a pericentric inversion in Japanese quail chromosome 4 as
compared to chicken chromosome 4. Twelve BAC clones specific for chicken
chromosome 4p and 4q showed the same order in quail as in chicken when FISH was
performed on lampbrush chromosomes. The centromeres of chicken and quail
chromosomes 4 seem to have formed independently after centric fusion of ancestral
chromosome 4 and a microchromosome.
PMID- 17028955
TI - Cytogenetic characterization of the sole Solea senegalensis (Teleostei:
Pleuronectiformes: Soleidae): Ag-NOR, (GATA)n, (TTAGGG)n and ribosomal genes by
one-color and two-color FISH.
AB - A cytogenetic analysis of the sole Solea senegalensis was carried out using
silver staining for the nucleolus organizer region (Ag-NOR) identification, one
color FISH for chromosomal mapping of 45S and 5S ribosomal DNAs (rDNAs), (GATA)n,
and (TTAGGG)n, and two-color FISH for co-localization of both rDNAs. The Ag-NORs
and the 45S rDNA were mapped to a medium-sized submetacentric chromosomal pair.
Hybridization with the 5S rDNA showed a major signal on the short arm of a medium
sized submetacentric chromosome pair and a minor signal on a centromeric site of
a small acrocentric chromosome pair. Differences in the Ag-NOR and 45S and 5S
rDNAs FISH signal sizes were observed between homologous chromosomes and among
individuals. A two-color FISH co-localized 45S and 5S rDNAs to a medium-sized
submetacentric chromosomal pair. The hybridization with the telomeric (TTAGGG)n
repeat displayed small signals at all chromosomal telomeres. Finally, the (GATA)n
probe produced dispersed and small hybridization signals on all chromosome
spreads, showing its ubiquitous existence in the genome. These results were
compared with those from other Pleuronectiformes and discussed in terms of
karyotype evolution.
PMID- 17028956
TI - Long L1 insertions in human gene introns specifically reduce the content of
corresponding primary transcripts.
AB - LINE-1 (L1) retrotransposons comprise about 17% of the human genome and include a
recently transposed set of Ta-L1 elements that are polymorphic in humans.
Although it is widely believed that L1s play an essential role in shaping and
functioning of mammalian genomes, the understanding of the impact of L1
insertions on gene expression is far from being comprehensive. Here we compared
hnRNA contents for allele pairs of genes heterozygous for Ta-L1 insertions in
their introns in human cell lines of various origin. We demonstrated that some Ta
L1 insertions correlated with decreased content of the corresponding hnRNAs. This
effect was characteristic of only nearly full-sized L1s and seemed to be tissue
specific.
PMID- 17028957
TI - Genic heterozygosity, chromosomal interchanges and fitness in rye: any
relationship?
AB - Relationship between heterozygosity at allozyme loci, chromosomal interchanges
and fitness was analyzed in a rye cultivar showing a polymorphism for such
rearrangements. Nine allozyme systems (ACO, ACPH, GOT, GPI, LAP, MDH, PER, PGD
and PGM) and five components of fitness (number of fertile tillers, total
offspring, egg cell fertility, flowers/ear and seeds/ear) were studied. The
estimated selection coefficients against interchange heterozygotes ranged from s
= 0.12 to s = 0.34. A significant effect of the genic heterozygosity on some
fitness components was observed in interchange heterozygotes (tillering and total
offspring), in their standard homozygous sibs (flowers/ear and seeds/ear) and in
the descendants of the crosses between standard karyotypes (flowers/ear,
seeds/ear and egg cell fertility). However, the main effect was linked to genetic
background associated to different crosses. Significant differences for Acph-1,
Gpi-1, Lap-1, Mdh-1, Mdh-4, Pgd-2 and Pgm-1 loci were also found in some of these
crosses although these differences were inconsistent. This suggests that probably
the allozyme loci analyzed were not directly contributing to the fitness and that
they are linked, in some cases, to different deleterious alleles depending on
both cross and locus. This fact could support the local effect hypothesis as
explanation although we do not discard the existence of some inbreeding level
(general effect hypothesis) since all crosses and loci studied show a overall
consistent trend of increased fitness with increased heterozygosity.
PMID- 17028958
TI - Conservation of pBuM-2 satellite DNA sequences among geographically isolated
Drosophila gouveai populations from Brazil.
AB - In this study, we have compared 34 repetition units of pBuM-2 satellite DNA of
individuals from six isolated populations of Drosophila gouveai, a cactophilic
member of Drosophila buzzatii cluster (repleta group). In contrast to the results
of previous morphological and molecular data, which suggest differentiation among
the D. gouveai populations, the sequences and the cluster analysis of pBuM-2
monomers showed that this repetitive element is highly conserved among the six D.
gouveai populations (97.8% similarity), indicating a slow rate of evolution of
pBuM-2 sequences at the population level. Probably, some homogenization
mechanisms of tandem sequences, such as unequal crossing or gene conversion, have
maintained the sequence similarity of pBuM-2 among D. gouveai populations.
Alternatively, such a result may be associated with a functional role of pBuM-2
sequences, although it is not understood at present.
PMID- 17028959
TI - The dynamic gene expression from different genetic systems for protein and lysine
contents of indica rice.
AB - The dynamic expression of genes for protein and lysine contents of rice grain
under different environments was carried out with time-dependent measures by
using the developmental genetic models for quantitative traits of triploid
endosperm in cereal crops. The results showed that the genetic effects,
especially genotype x environment (GE) interaction effects from the genes
expression of different genetic systems including triploid endosperm, cytoplasm
and diploid maternal plant were important for the performance of both nutrient
quality traits at all developmental times/stages of rice grain. The conditional
genetic variance analysis found that the activation of quantitative genes
especially from endosperm and maternal plant genetic systems for protein and
lysine contents was gradually carried through the developmental process of rice
grain. The net genetic effects showed that the new expression of quantitative
genes for protein and lysine contents was more active at late filling stage (15
21 days after flowering) and maturity stage (22-28 days) of rice grain. Also the
sequential expression of cytoplasmic genes cannot be ignorable for the
development of nutrient quality traits. The phenomena that some genes could
continuously express for several developmental stages or the genes expression
could be interrupted among developmental stages of rice grain was detected
especially for net endosperm additive main effects or maternal additive main
effects. The differences of genetic relationships from different genetic systems
were found for protein and lysine contents among developmental times of rice
grain.
PMID- 17028960
TI - Seasonal dynamics of population genetic structure in cryptic taxa of the
Pellioditis marina complex (Nematoda: Rhabditida).
AB - The distribution patterns and genetic structure of the Pellioditis marina species
complex in Belgium and The Netherlands were compared between four consecutive
seasons. Different types of habitats (coast, estuary, semi-estuary and lake) with
different degrees of connectivity were sampled. In addition, each habitat type
was characterised by either temporal or permanent algal deposits. We screened 426
bp of the mitochondrial cytochrome oxidase c (COI) gene with the single-strand
conformation polymorphism (SSCP) method in 1615 individuals of Pellioditis
marina. The 51 haplotypes were divided into four (sympatric) lineages, with
divergences ranging from 0.25 to 10.6%. Our results show that the lineages have
different temporal dynamics, which may be linked to abiotic factors. Analysis of
Molecular Variance (AMOVA) indicated a significant structuring in the PmI
lineage, which correlated with habitat characteristics and which changed over
time (Mantel, r = 0.51; p = 0.126). Intrapopulational diversity was similar in
all locations, and temporal changes in haplotype frequencies were not higher in
temporary than in permanent algal deposits. Instead, the results of the temporal
survey indicated that (some) P. marina populations are characterised by a
metapopulation structure. It is emphasized that a complete and correct
interpretation of processes causing genetic structuring within species and of the
genetic structure itself can only be done when analyses are performed at several
time points.
PMID- 17028961
TI - RAPD variation and population genetic structure of Physalaemus cuvieri (Anura:
Leptodactylidae) in Central Brazil.
AB - Studies about the organization of the genetic variability and population
structure in natural populations are used either to understand microevolutionary
processes or the effects of isolation by human-inducted landscape modifications.
In this paper, we analyzed patterns of genetic population structure using 126
RAPD loci scored for 214 individuals of Physalaemus cuvieri, sampled from 18
local populations. Around 97% of these loci were polymorphic. The among
population variation component (Phi(ST)) obtained by AMOVA was equal to 0.101 and
theta B obtained using a Bayesian approach for dominant markers was 0.103.
Genetic divergence, analyzed by Mantel spatial correlogram, revealed only a short
distance significant correlation between genetic and geographic distances. This
is expected if low levels of population differentiation, due to high abundance
buffering the effect of stochastic processes, are combined with low spatially
restricted gene flow. Although this may be consistent with the current knowledge
of species' biology, the spatial distribution of local populations observed in
this study also suggest that, at least in part, recent human occupation and
habitat fragmentation may also explain part of the interpopulational component of
the genetic variation.
PMID- 17028962
TI - Evolutionary chromosomal differentiation among four species of Conoderus
Eschscholtz, 1829 (Coleoptera, Elateridae, Agrypninae, Conoderini) detected by
standard staining, C-banding, silver nitrate impregnation, and CMA3/DA/DAPI
staining.
AB - The speciose Brazilian Elateridae fauna is characterized by high karyotypic
diversity, including one species (Chalcolepidius zonatus Eschscholtz, 1829) with
the lowest diploid number within any Coleoptera order. Cytogenetic analysis of
Conoderus dimidiatus Germar, 1839, C. scalaris (Germar, 1824,) C. ternarius
Germar, 1839, and C. stigmosus Germar, 1839 by standard and differential staining
was performed with the aim of establishing mechanisms of karyotypic
differentiation in these species. Conoderus dimidiatus, C. scalaris, and C.
ternarius have diploid numbers of 2n(male) = 17 and 2n(female) = 18, and a X0/XX
sex determination system, similar to that encountered in the majority of
Conoderini species. The karyotype of C. stigmosus was characterized by a diploid
number of 2n = 16 and a neoXY/neoXX sex determination system that was highly
differentiated from other species of the genus. Some features of the mitotic and
meiotic chromosomes suggest an autosome/ancestral X chromosome fusion as the
cause of the neoXY system origin in C. stigmosus. C-banding and silver
impregnation techniques showed that the four Conoderus species possess similar
chromosomal characteristics to those registered in most Polyphaga species,
including pericentromeric C band and autosomal NORs. Triple staining techniques
including CMA3/DA/DAPI also provided useful information for differentiating these
Conoderus species. These techniques revealed unique GC-rich heterochromatin
associated with NORs in C. scalaris and C. stigmosus and CMA3-heteromorphism in
C. scalaris and C. ternarius.
PMID- 17028963
TI - Interplasmid transposition demonstrates piggyBac mobility in vertebrate species.
AB - The piggyBac transposon is an extremely versatile helper-dependent vector for
gene transfer and germ line transformation in a wide range of invertebrate
species. Analyses of genome sequencing databases have identified piggyBac
homologues among several sequenced animal genomes, including the human genome. In
this report we demonstrate that this insect transposon is capable of
transposition in primate cells and embryos of the zebrafish, Danio rerio.
piggyBac mobility was demonstrated using an interplasmid transposition assay that
has consistently predicted the germ line transformation capabilities of this
mobile element in several other species. Both transfected COS-7 primate cells and
injected zebrafish embryos supported the helper-dependent movement of tagged
piggyBac element between plasmids in the characteristic cut-and-paste, TTAA
target-site specific manner. These results validate piggyBac as a valuable tool
for genetic analysis of vertebrates.
PMID- 17028964
TI - High efficiency of a double-screening method on single P-element insertion lines
to identify quantitative trait mutants in Drosophila melanogaster.
AB - Enhancer trap P-element insertion has become a common method for generating new
mutations in Drosophila melanogaster. When this method is used to isolate mutants
for quantitative traits, an appropriate control must be established to define
normal and mutant phenotypes. Considering that enhancer-trap lines are generated
by crossing several strains, usually with no homogeneous genetic background, no
clear control strain can be selected. Previous reports tried to overcome this
problem by homogenizing the genetic background of the original lines. However,
this is not the most common scenario, especially when functional phenotypes are
studied in previously generated lines. Without such caution, is it possible to
identify functional mutants among P-element insertion lines? We tested this for
olfactory preference, a quantitative trait. Using as control measurement the
average phenotype of 30 simultaneously generated P-element insertion lines with
preferential reporter-gene expression in olfactory reception organs, we found
that 25 of the lines exhibited mutant phenotypes in response to one or several of
5 tested odorants. Additional tests showed that the efficiency of the method for
detecting olfactory mutations exceeded 60% even for such a small number of tested
odorants. According to these results this approach greatly facilitates the
identification of putative abnormal phenotypes, which must be extensively
confirmed afterwards.
PMID- 17028965
TI - The association between inversion In(3R)Payne and clinally varying traits in
Drosophila melanogaster.
AB - In Drosophila melanogaster, inversion In(3R)Payne increases in frequency towards
low latitudes and has been putatively associated with variation in size and
thermal resistance, traits that also vary clinally. To assess the association
between size and inversion, we obtained isofemale lines of inverted and standard
karyotype of In(3R)Payne from the ends of the Australian D. melanogaster east
coast cline. In the northern population, there was a significant association
between In(3R)Payne and body size, with standard lines from this population being
relatively larger than inverted lines. In contrast, the inversion had no
influence on development time or cold resistance. We strengthened our findings
further in a separate study with flies from populations from the middle of the
cline as well as from the cline ends. These flies were scored for wing size and
the presence of In(3R)Payne using a molecular marker. In females, the inversion
accounted for around 30% of the size difference between cline ends, while in
males the equivalent figure was 60%. Adaptive shifts in size but not in the other
traits are therefore likely to have involved genes closely associated with
In(3R)Payne. Because the size difference between karyotypes was similar in
different populations, there was no evidence for coadaptation within populations.
PMID- 17028966
TI - Genetic diversity and population structure of Lamiophlomis rotata (Lamiaceae), an
endemic species of Qinghai-Tibet Plateau.
AB - Lamiophlomis rotata (Lamiaceae), a perennial medicinal herb, is endemic to the
Qinghai-Tibet Plateau. A total of 188 individuals from eight natural populations
of L. rotata in Qinghai-Tibet Plateau (four from Tibet, two from Yunnan, and two
from Qinghai) were analyzed using intersimple sequence repeats (ISSR) and
randomly amplified polymorphic DNA (RAPD) techniques. Our results revealed that
the level of genetic variation in L. rotata was relatively high (P = 94.85%, I =
0.440 +/- 0.220, H(T) = 0.289 +/- 0.028). Three genetic groups corresponding to
the three geographic regions were detected, suggesting significant geographic
structure. Our results suggest that the highly structured geographic pattern
found in L. rotata might represent diverging evolutionary processes associated
with the uplifting of the Qinghai-Tibet Plateau and Quaternary climatic
oscillations. These findings imply that as many populations as possible should be
preserved in situ for the conservation of this species. Given their genetic
variability and peripheral distribution, Qinghai and Yunnan populations should be
assigned priority for conservation. Optimal harvesting strategies, domestication
and tissue culture of L. rotata should be developed as soon as possible to
guarantee its sustainable use.
PMID- 17028967
TI - Isolation and characterization of a novel semi-lethal Arabidopsis thaliana mutant
of gene for pentatricopeptide (PPR) repeat-containing protein.
AB - A novel Arabidopsis thaliana mutant of one member of the pentatricopeptide repeat
(PPR) gene family has been identified among T-DNA insertion lines. Tagging of the
At1g53330 gene caused the appearance of a semi-lethal mutation with a complex
phenotypic expression from embryo lethality associated with the abnormal pattern
of cell division during globular to heart transition to fertile plants with just
subtle phenotypic changes. The PPR protein At1g53330.1 was predicted to be
targeted to mitochondria by TargetP and MitoProt programs. Complementation
analysis confirmed that the phenotype is a result of a single T-DNA integration.
A thorough functional analysis of this mutant aimed at finding a particular
organelle target of At1g53330.1 protein will follow.
PMID- 17028968
TI - High RAPD but no cpDNA sequence variation in the endemic and endangered plant,
Heptacodium miconioides Rehd. (Caprifoliaceae).
AB - Heptacodium miconioides Rehd. is an endangered species endemic to China and has
suffered rapid decrease of distribution range and population size. This species
has been disappeared in central China where the modal specimen was collected. We
analyzed the genetic variation of the remaining populations to reveal whether the
genetic diversity also suffered decrease and to provide some suggestions for
conservation. All the nine known remaining populations were sampled. Genetic
variation was analyzed based on RAPD markers and two fragments of cpDNA sequence,
intergenic spacers of petG-trnP and trnS-trnG. No variation was observed in the
two fragments of cpDNA sequence. However, the species exhibited high level of
RAPD variation compared to other threatened or rare plants. Measures of genetic
diversity within populations were strongly related to the log of estimated
population size, indicating that large populations usually have more genetic
diversity than that of small ones. About 25% of the variation was partitioned
among populations. Significant relationship was observed between differentiation
and geographical distance, indicating a pattern of isolation-by-distance. Given
for few populations remaining, all the populations should be protected and urgent
efforts be paid on the small populations to avoid their local extinction.
PMID- 17028969
TI - Testing alternative methods for purging genetic load using the housefly (Musca
domestica L.).
AB - When a population faces long-term inbreeding, artificial selection, in principle,
can enhance natural selection processes for purging the exposed genetic load.
However, strong purge pressures might actually decrease fitness through the
inadvertent fixation of deleterious alleles and allelic combinations. We tested
lines of the housefly (Musca domestica L.) for the effectiveness of artificial
selection to promote the adaptation to small population size. Specifically,
replicate populations were held at average census sizes of 54 for nine
generations or 30 for 14 generations while being subjected to artificial
selection pressure for increased fitness in overall mating propensity (i.e., the
proportion of virgin male-female pairs initiating copulation within 30 min),
while also undergoing selection to create differences among lines in multivariate
components of courtship performance. In the 14-generation experiment, a subset of
the lines were derived from a founder-flush population (i.e., derived from three
male-female pairs). In both experiments, we also maintained parallel non
selection lines to assess the potential for natural purging through serial
inbreeding alone. Sub-populations derived from a stock newly derived from the
wild responded to artificial selection for increased mating propensity, but only
in the short-term, with eventual rebounds back to the original levels. Serial
inbreeding in these lines simply reduced mating propensity. In sub-populations
derived from the same base population, but 36 generations later, both artificial
selection and serial inbreeding increased mating propensity, but mainly to
restore the level found upon establishment in the laboratory. Founder-flush lines
responded as well as the non-bottlenecked controls, so we base our major
conclusions on the comparisons between fresh-caught and long-term laboratory
stocks. We suggest that the effectiveness of the alternative purge protocols
depended upon the amount of genetic load already exposed, such that prolonged
periods of relaxed or altered selection pressures of the laboratory rendered a
population more responsive to purging protocols.
PMID- 17028970
TI - Molecular evolution and functional specialization of chalcone synthase
superfamily from Phalaenopsis orchid.
AB - Plant genomes appear to exploit the process of gene duplication as a primary
means of acquiring biochemical and developmental flexibility. The best example is
the gene encoding chalcone synthase (CHS, EC2.3.1.74), the first committed step
in flavonoid biosynthesis. In this study, we examined the molecular evolution of
three CHS family members of Phalaenopsis including a novel chs gene (phchs5),
which is slowly evolved. The inferred phylogeny of the chs genes of Phalaenopsis
with other two orchid plants, Bromoheadia finlaysoniana and Dendrobium hybrid,
suggested that gene duplication and divergence have occurred before divergence of
these three genera. Relatively quantitative RT-PCR analysis identified expression
patterns of these three chs genes in different floral tissues at different
developmental stages. Phchs5 was the most abundantly expressed chs gene in floral
organs and it was specifically transcribed in petal and lip at the stages when
anthocyanin accumulated (stage1-4). Phchs3 and phchs4 were expressed at much
lower levels than phchs5. Phchs3 was expressed in pigmented tissue (including
lip, petal and sepal) at middle stages (stages 2-4) and in colorless reproductive
tissue at late stage (stage 5). Phchs4 was only expressed in petal at earlier
stages (stage 1-3) and in lip at middle stage (stage 4). These results present
new data on differentiation of gene expression among duplicate copies of chs
genes in Phalaenopsis.
PMID- 17028971
TI - Morgane, a new LTR retrotransposon group, and its subfamilies in wheats.
AB - Transposable elements are the main components of grass genomes, especially in
Triticeae species. In a previous analysis, we identified a very short element,
Morgane_CR626934-1; here we describe more precisely this unusual element.
Morgane_CR626934-1 shows high sequence identity (until 98%) with ESTs belonging
to other possible small elements, expressed under abiotic and biotic stress
conditions. No putative functional polyprotein could be identified in all of
these different Morgane-like sequences. Moreover, elements from the
Morgane_CR626934-1 subfamily are found only in wheats and Agropyrum genomes and
among these species, only Ae. tauschii and T. aestivum present a high copy number
of these elements. They are highly conserved in wheat genomes (95.5%). Based on
the uncommon characteristics of the described Morgane-like elements, we proposed
to classify them in a new group within the Class I LTR retrotransposon, the
Morgane group.
PMID- 17028972
TI - Differential organellar inheritance in Passiflora's (Passifloraceae) subgenera.
AB - Four chloroplast (cp), one mitochondrial (mt), and one ribosomal nuclear (ITS)
DNA regions were studied in four artificial and one natural interspecific
Passiflora hybrids. The ITS results confirmed their hybrid origin and all mtDNAs
were maternally inherited. The same, however, was not true for cpDNA. The four
hybrids (three artificial and one natural) derived from species of the Passiflora
subgenus showed a cpDNA paternal inheritance, while the one involving taxa of the
Decaloba subgenus gave evidence of maternal transmission. These results are of
significance for the ongoing studies which are being performed on the molecular
evolution of this genus and furnish important background for investigations aimed
at clarifying the factors which determine cpDNA inheritance.
PMID- 17028973
TI - Repetitive DNA sequences include retrotransposons in genomes of the
Glomeromycota.
AB - Twenty-five repetitive elements are first described in the genomes of the
arbuscular mycorrhizal (AM) fungi Gigaspora margarita, Gig. rosea and Glomus
mosseae. Nineteen repetitive DNA sequences isolated by genomic library screening
and four by self-priming PCR had no homology to known DNA sequences, except for
two Gig. margarita sequences and one Gig. rosea sequence which showed amino acid
similarity to retrotransposons. Part of the Gig. rosea sequence was also similar
to a DNA transposon. Two other retrotransposon sequences were isolated using PCR
targeting of reverse transcriptase and ribonuclease H domains. Evidence is
provided for three gypsy-like LTR retrotransposon and two non-LTR retrotransposon
sequences in the AM fungal genomes. Four contain stop codons indicating that they
cannot be active. Expression of three retrotransposons was not detected in
germinating spores or intraradical hyphae of Gig. margarita. Southern blot
analyses indicated that these three sequences are dispersed in the genome and
that two are methylated. Sequence analysis of different GmarLTR1 copies showed
they have undergone mutations by transitions, which may have been induced by
cytosine methylation. Transposable elements may have played a major role in
shaping genome structure and size during evolution of the Glomeromycota.
PMID- 17028974
TI - Estimating effects of a single gene and polygenes on quantitative traits from a
diallel design.
AB - A genetic model is developed with additive and dominance effects of a single gene
and polygenes as well as general and specific reciprocal effects for the progeny
from a diallel mating design. The methods of ANOVA, minimum norm quadratic
unbiased estimation (MINQUE), restricted maximum likelihood estimation (REML),
and maximum likelihood estimation (ML) are suggested for estimating variance
components, and the methods of generalized least squares (GLS) and ordinary least
squares (OLS) for fixed effects, while best linear unbiased prediction, linear
unbiased prediction (LUP), and adjusted unbiased prediction are suggested for
analyzing random effects. Monte Carlo simulations were conducted to evaluate the
unbiasedness and efficiency of statistical methods involving two diallel designs
with commonly used sample sizes, 6 and 8 parents, with no and missing crosses,
respectively. Simulation results show that GLS and OLS are almost equally
efficient for estimation of fixed effects, while MINQUE (1) and REML are better
estimators of the variance components and LUP is most practical method for
prediction of random effects. Data from a Drosophila melanogaster experiment
(Gilbert 1985a, Theor appl Genet 69:625-629) were used as a working example to
demonstrate the statistical analysis. The new methodology is also applicable to
screening candidate gene(s) and to other mating designs with multiple parents,
such as nested (NC Design I) and factorial (NC Design II) designs. Moreover, this
methodology can serve as a guide to develop new methods for detecting
indiscernible major genes and mapping quantitative trait loci based on mixture
distribution theory. The computer program for the methods suggested in this
article is freely available from the authors.
PMID- 17028976
TI - Is survivin expression nevertheless related to disease outcome in breast cancer?
PMID- 17028975
TI - Hypoxia-inducible factor-1alpha correlates with MET and metastasis in node
negative breast cancer.
AB - The mechanism of tumor hypoxia promoting metastasis remains uncertain. Hypoxia
inducible factor-1alpha (HIF-1alpha) is a key mediator of the cellular response
to hypoxia and binds the met promoter, resulting in increased expression of MET.
In breast cancer, MET overexpression is associated with death caused by
metastatic disease. Aim of this study is to investigate the role of HIF-1alpha in
MET expression and metastasis in lymph node negative breast cancer. We recruited
a homogeneous cohort of 104 patients with T(1-2)N(0)M(0) breast carcinoma, who
had undergone primary surgery. Fifty-three patients had distant metastases and 51
patients had no evidence of disease for more than 10 years. We analyzed the
expressions of HIF-1alpha and MET in these patients using immunohistochemistry.
HIF-1alpha and MET were positively correlated (Spearman's rank correlation
coefficient, 0.35; P < 0.01), were independent predictors of distant metastasis
(P = 0.002 and P = 0.03, respectively), and correlated with poor 10-year disease
free survival rate (P < 0.001 for both). Furthermore, co-overexpression of HIF
1alpha and MET was a significant independent predictor of distant metastasis (odd
radio, 10.78; P < 0.001), and patients with co-overexpression had a significantly
worse 10-year disease-free survival rate. The results provide evidence that tumor
hypoxia promotes metastasis through the induction of MET overexpression by HIF
1alpha and emphasize the promising status of HIF-1alpha as a therapeutic target
against metastasis in node-negative breast cancer.
PMID- 17028977
TI - Simultaneous two-color spectral fluorescence lymphangiography with near infrared
quantum dots to map two lymphatic flows from the breast and the upper extremity.
AB - Due to their small size and poor access, the lymphatic function has been
difficult to study in vivo. Especially difficult is the mapping of lymphatic
drainage from two basins into the same node. Quantum dots can be used to perform
multicolor images with high fluorescent intensity and are of a nano-size size
suitable for lymphatic imaging via direct interstitial injection. Here we show
simultaneous two-color in vivo wavelength-resolved spectral fluorescence
lymphangiography using two near infrared quantum dots with different emission
spectra, which allow non-invasive and simultaneous visualization of two separate
lymphatic flows draining the breast and the upper extremity and variations in the
drainage patterns and the water sheds within the axillary node. Two-color
spectral fluorescence lymphangiography can provide insight into mechanisms of
drainage from different lymphatic basins that may lead to sentinel lymph nodes
detection of the breast cancer as well as prevention of complications such as
lymphedema of the arm.
PMID- 17028978
TI - Physician and patient characteristics associated with outpatient breast cancer
screening recommendations in the United States: analysis of the National
Ambulatory Medical Care Survey Data 1996-2004.
AB - BACKGROUND: The primary goal of breast cancer screening tests is to find cancer
at an early stage before a person has any symptoms. Evidence suggests that
screening examinations such as mammography and clinical breast examinations (CBE)
are effective in early detection of breast cancer. Physician recommendation is an
important reason many women undergo screening. This study examined the physician
and patients related factors associated with physician recommendations for breast
cancer screening in the United States (US) outpatient settings. METHODS: This
cross-sectional study used data from the National Ambulatory Medical Care Survey
(NAMCS) from 1996-2004. Women aged >or=40 years were included in the study
sample. Multivariate logistic regression analyses were used to study the
objectives. RESULTS: Weighted analysis indicated that physicians performed 198
million CBEs and made 110 million mammography recommendations over the study
period (1996-2004). Patients' age, duration of visits, history of previous breast
cancer diagnosis, and source of insurance were significant predictors of
screening recommendations in this population. Obstetricians and gynecologists
were more likely to perform a CBE and recommend mammography than other specialty
physicians. CONCLUSIONS: These findings indicated that there were certain
disparities regarding the physician recommendations of breast cancer screening
for women in the US outpatient settings.
PMID- 17028979
TI - Results from an observational trial with oral vinorelbine and trastuzumab in
advanced breast cancer.
AB - PURPOSE: We evaluated the efficacy and tolerability of oral vinorelbine plus
trastuzumab (OV + T) in Her2 positive advanced breast cancer as first line
chemotherapy or after progressing on earlier treatment. PATIENTS AND METHODS:
Thirty consecutive patients (median age: 59 years) were included. Patients
received OV in a dose of 60 mg/m(2) on day 1 and 8, q=21, without dose
escalation. Trastuzumab was administered every 3 weeks at a dose of 6 mg/kg
bodyweight after a loading dose of 8 mg/kg. Response was evaluated every three
cycles using UICC criteria. Time to progression (TTP) and overall survival (OS)
were estimated using the Kaplan-Meier product limit method. A multivariate
analysis was performed to evaluate factors potentially influencing response rate
and TTP. RESULTS: Median time of observation was 20 months. We observed a
complete response in 18% of patients, partial remission in 50%, stable disease
>or= 6 months in 21%, and progressive disease in 11%. TTP was median 9 months. OS
was not reached. Response rate and TTP were influenced by line of treatment only.
The main toxicities consisted of neutropenia and nausea. CONCLUSIONS: OV + T
appears to be an effective and safe treatment option in advanced breast cancer at
the dose and schedule chosen.
PMID- 17028980
TI - Are there racial differences in breast cancer treatments and clinical outcomes
for women treated at M.D. Anderson Cancer Center?
AB - PURPOSE: To determine the influence of race on breast cancer treatment and on
recurrence and breast cancer specific death. PATIENTS AND METHODS: The study
population consisted of 6,054 African-American or white women who were diagnosed
with breast cancer and received at least one of the treatments including
mastectomy or breast conservative surgery, radiation, adjuvant chemotherapy, neo
adjuvant chemotherapy, and adjuvant endocrine therapy at M.D. Anderson Cancer
Center between June 1997 and February 2005. The clinical outcomes were disease
free survival and breast-cancer-specific survival. Logistic regression analysis
was performed to investigate if race was associated with the selection of each
primary treatment while adjusting for tumor characteristics at diagnosis. Cox
proportional hazards model was used to determine the effect of race on recurrence
free survival and breast-cancer-specific survival controlling for tumor
characteristics, presence of co-morbidity conditions and use of these treatments.
RESULTS: The use of any primary treatment for breast cancer was not significantly
different by race after adjusting for tumor characteristics and co-morbidity
conditions. Although tumor characteristics at diagnosis explained the major
differences in clinical outcomes, race remained an independent prognostic factor
for breast-cancer-specific survival (P=0.002), and a marginally significant
factor for disease-free survival (P=0.063) in multivariate analyses. CONCLUSION:
Equal treatment may not lead to equal clinical outcomes given similar tumor
characteristics at diagnosis. To reduce racial differences in breast cancer
recurrence and survival, it is important to have a better understanding of
differences in tumor biology by race and to promote the use of early detection
programs among African-American women.
PMID- 17028981
TI - 15-deoxy-Delta(12,14)-prostaglandin J2 inhibits G2-M phase progression in human
breast cancer cells via the down-regulation of cyclin B1 and survivin expression.
AB - The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d
PGJ(2)) exerts a growth inhibitory effect on cancer cells, and this effect is
linked to the induction of apoptosis or cell cycle arrest. Induction of apoptosis
by 15d-PGJ(2) is associated with the down-regulation of anti-apoptotic proteins.
G(0)-G(1)-->S phase progression is inhibited by 15d-PGJ(2) via the degradation of
cyclin D1. In this study, we further investigated the mechanism by which 15d
PGJ(2) inhibits cancer cell growth by using the breast cancer cell lines MCF-7
and T-47D. Treatment with 20 microM 15d-PGJ(2) for 72 h completely blocked the
growth in both cell lines. However, the proportions of apoptotic MCF-7 and T-47D
cells were 21.1% and 40.9%, respectively, indicating that the induction of
apoptosis did not appear to fully account for growth inhibition by 15d-PGJ(2).
Cell cycle analysis using cells synchronized at the G(0)-G(1) or S phase revealed
that 15d-PGJ(2) blocked not only G(0)-G(1)-->S phase progression but also G(2)-M
phase progression. The expression of both cyclins D1 and B1 was decreased by 15d
PGJ(2). Furthermore, 15d-PGJ(2) inhibited aurora-B kinase activity, which
coincided with the down-regulation of survivin. Thus, 15d-PGJ(2) induced cell
cycle arrest at the G(2)-M phase via inhibition of cyclin B1 expression and
aurora-B kinase activity. We conclude that survivin may be an important target
for 15d-PGJ(2), and its down-regulation may lead to a decrease in aurora-B kinase
activity.
PMID- 17028982
TI - Common non-synonymous polymorphisms in the BRCA1 Associated RING Domain (BARD1)
gene are associated with breast cancer susceptibility: a case-control analysis.
AB - The BRCA1 Associated RING Domain (BARD1) gene has been identified as a high
penetrance gene for breast cancer, whose germline and somatic mutations were
reported in both non-BRCA1/2 hereditary site-specific and sporadic breast cancer
cases. BARD1 plays a crucial role in tumor repression, along with its
heterodimeric partner BRCA1. In the current study, we tested the hypothesis that
common non-synonymous polymorphisms in BARD1 are associated with breast cancer
susceptibility in a case-control study of 507 patients with incident breast
cancer and 539 frequency-matched cancer-free controls in Chinese women. We
genotyped all three common (minor allele frequency (MAF)>0.10) non-synonymous
polymorphisms (Pro24Ser, Arg378Ser, and Val507Met) in BARD1. We found that the
BARD1 Pro24Ser variant genotypes (24Pro/Ser and 24Ser/Ser) and Arg378Ser variant
homozygote 378Ser/Ser were associated with a significantly decreased breast
cancer risk, compared with their wild-type homozygotes, respectively.
Furthermore, a significant locus-locus interaction was evident between Pro24Ser
and Arg378Ser (P(int )= 0.032). Among the 378Ser variant allele carriers, the
24Pro/Pro wild-type homozygote was associated with a significantly increased
breast cancer risk (adjusted OR=1.81, 95% CI=1.11-2.95), but the subjects having
24Pro/Ser or Ser/Ser variant genotypes had a significantly decreased risk
(adjusted OR=0.74, 95% CI=0.56-0.99). In stratified analysis, this locus-locus
interaction was more evident among subjects without family cancer history, those
with positive estrogen receptor (ER) and individuals with negative progesterone
receptor (PR). These findings indicate that the potentially functional
polymorphisms Pro24Ser and Arg378Ser in BARD1 may jointly contribute to the
susceptibility of breast cancer.
PMID- 17028983
TI - Changes in risk of death from breast cancer with season and latitude: sun
exposure and breast cancer survival in Norway.
AB - The Norwegian counties can conveniently be divided in three groups with different
annual UV exposures and different incidence rates of squamous cell carcinoma
(SCC) of the skin. In view of the hypothesis that latitude and season of
diagnosis may play a role for breast cancer progression, the prognosis of breast
cancer as determined for summer and winter diagnosis, were evaluated in the three
residential regions. Two age groups were analysed separately (stratification at
50 years). For all regions, and for all ages, the prognosis was best for women
diagnosed in the summer season (Relative risk (RR) of death was 15-25% lower for
summer diagnosis versus winter diagnosis). There was no significant seasonal
variation of the number of new cases. For women diagnosed before the age of 50, a
geographical gradient in cancer prognosis was also found (RR of death 0.6, 95%
CI: 0.5-0.7 for cases diagnosed in southeast Norway and RR of death 0.8, 95% CI:
0.6-1.1 for diagnosis in the north of Norway). This is in agreement with a 1.5
times larger annual UV exposures and 3-4 times larger incidence rates of SCC in
the southeast region when compared with the north region. For women diagnosed
after the age of 50, no significant difference was found between the three
regions. Despite a 17% higher vitamin D intake from food in north of Norway no
difference in cancer survival was found for diagnosis during winter (when no
significant differences in the levels of UV exposure can be detected between
regions). The overall data support our earlier hypothesis that season of
diagnosis and therapy start improves the survival for breast cancer.
PMID- 17028984
TI - Paget's disease of the breast: accuracy of preoperative assessment.
AB - BACKGROUND: Routine preoperative assessment may not accurately assess the extent
of underlying cancer in patients with Paget's disease (PD) of the breast. We
performed this study to correlate findings on clinical examination and
mammography with pathologic results and outcomes in women with PD. METHODS: An
IRB-approved retrospective review identified all patients with PD between 1975
and 2000. Clinical exam and mammographic findings were recorded, and information
on recurrence and survival was obtained from medical records. RESULTS: Univariate
analyses identified palpable mass and suspicious mammogram as risk factors
significantly associated with a worse outcome. Patients were therefore
categorized by combinations of these two preoperative factors. All patients with
a palpable mass and a suspicious mammogram had invasive cancer. In the subgroup
of 40 women with a benign mammogram and no palpable mass, invasive cancer
occurred in 5% and the majority (68%) had ductal carcinoma in situ which extended
beyond the nipple. Women with a palpable mass and a suspicious mammogram had
significantly worse survival compared to those with a benign mammogram and no
palpable mass (P = 0.008). With a median follow-up of 6.4 years, five local
recurrences occurred in patients with invasive cancer who underwent mastectomy.
CONCLUSION: In women with PD, a palpable mass or suspicious mammogram portends a
high likelihood of invasive cancer. Underlying cancer is common even in women
with a benign mammogram and no palpable mass. Although breast conservation is an
attractive option in patients with PD, mammography and physical exam may
significantly underestimate the presence and extent of underlying disease.
PMID- 17028985
TI - Improvement of best practice in early breast cancer: actionable surgeon and
hospital factors.
AB - To identify actionable elements for improving best practice, this study examined
the relative effects of patient, surgeon and hospital factors on surgical
treatment variation of 2,929 early breast cancer patients, diagnosed from January
1998 to January 2002 in the region of the Comprehensive Cancer Centre North
Netherlands. Multilevel logistic regression was used to analyze the
hierarchically structured data. Apart from the patient level, 43.3% of the
treatment variation was due to the hospital and 56.7% to the surgeon, after
adjustment for patient characteristics. Although hospital factors like volume,
teaching status, and management and policy contributed to this variation,
multidisciplinary care seemed the most important actionable hospital factor.
Although the surgeon was shown to be an important starting point for quality
improvement, actionable elements seemed difficult to identify as factors like
surgeon experience and volume were not conclusive and significant variance on
this level remained (sigma2 = 0.149, SE 0.053). We conclude that
multidisciplinary care can improve best practice and that further research into
actionable surgeon factors is needed.
PMID- 17028986
TI - Risk factors for breast cancer in older women: the relative contribution of bone
mineral density and other established risk factors.
AB - AIM: To determine the contribution of bone mineral density (BMD) to breast cancer
risk relative to other established breast cancer risk factors in postmenopausal
women with osteoporosis. METHODS: Data for this analysis comprised those
collected from women randomized to placebo in the MORE and CORE trials (N =
2,576). Risk factors measured at baseline included age, family history of breast
cancer, estradiol level, body mass index, prior hormone therapy, BMD and
vertebral fracture status. Cox proportional hazards regression models were used
to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:
Over a total of 13,698 woman-years of follow-up, 65 incident breast cancers
occurred. In univariate analyses, older age and family history of breast cancer
were the strongest predictors of breast cancer risk, associated with a 2.4- and
2.6-fold increase in breast cancer incidence. A higher estradiol level was
associated with a 1.9-fold increase in breast cancer incidence. The association
between femoral neck BMD and breast cancer incidence was only significant after
adjustment for age (P = 0.03). The final multivariable model included age, family
history, estradiol, BMD, and the BMD-estradiol interaction since the effect of
BMD on breast cancer varied by estradiol level (interaction P-value, 0.04); in
those with a lower estradiol level, a higher BMD was associated with a 2.6-fold
increased in breast cancer. CONCLUSION: Overall, BMD is a relatively weak
predictor of breast cancer risk in these postmenopausal women with osteoporosis,
after taking into consideration age, family history and endogenous estradiol
level.
PMID- 17028987
TI - Legumain expression as a prognostic factor in breast cancer patients.
AB - Invasive tumor cells and their microenvironments are enriched with a broad
spectrum of different proteases. Legumain, a novel asparaginyl endopeptidase, has
been observed to be highly expressed in several types of solid tumors. However,
there is no data available identifying the relationship of legumain expression
and clinicopathologic or biological variables in invasive breast cancer. For the
first time, the prevalence of legumain expression in invasive breast cancer (n =
432) and non-neoplastic breast tissues (n = 128) was investigated by
immunohistochemistry. Three staining patterns were observed in the cytoplasm:
diffuse positivity, tiny dots and vesicles. Whereas vesicular positivity in the
majority of tumor cells was significantly correlated to an adverse outcome,
cytoplasmic and dot-like staining showed no prognostic effect. Vesicular
positivity was observed in 24% of carcinomas, but only in one case of non
neoplastic breast tissue (<1%; proliferative mastopathy). This staining pattern
was found to be independent of other factors analysed as grading, nodal status or
HER2 expression. Besides being of prognostic value, legumain might prove to be an
important predictive factor in breast cancer, since its unique cleavage
specificity is already used in prodrug activation strategies.
PMID- 17028988
TI - Correlates of physical activity level in breast cancer survivors participating in
the Women's Healthy Eating and Living (WHEL) Study.
AB - BACKGROUND: Physical activity levels among breast cancer survivors are typically
low, and knowledge of the correlates of increased physical activity among cancer
survivors is limited. The purpose of this study was to examine factors that are
associated with physical activity or inactivity among breast cancer survivors.
METHODS: Data from 3088 women participating in the Women's Healthy Eating and
Living (WHEL) Study, collected prior to randomization, were the focus of the
current analyses. Self-reports of physical activity levels, quality of life,
depression, and dietary intakes were collected. Pearson correlation analyses were
employed to examine the associations among these variables, and multiple
regression analyses were performed to examine the relationship between selected
health behaviors and physical activity levels, after controlling for demographic,
breast cancer-related, and psychosocial variables. RESULTS: Demographic and
psychosocial variables were related to physical activity levels (P < 0.001 for
all). Cancer treatment type and cancer stage were correlated with survivors'
physical activity levels (P < 0.01), but the associations were no longer
significant after controlling for demographic variables. Physical activity levels
were strongly associated with other health behaviors, especially dietary intakes
(P < 0.001), even after controlling for demographic, cancer-related, and
psychosocial factors. CONCLUSION: Low physical activity levels in breast cancer
survivors are associated with specific behavioral and other factors, which can be
considered as indicators of women at higher risk. Findings of significant
differences in physical activity levels based on demographic characteristics
suggest the importance of promoting physical activity particularly among breast
cancer survivors of ethnic minority or lower education levels.
PMID- 17028989
TI - Transcriptome analysis reveals an osteoblast-like phenotype for human osteotropic
breast cancer cells.
AB - Metastatic breast cancer cells exhibit the selective ability to seed and grow in
the skeleton. We and others have previously reported that human breast tumors
which metastasize to the skeleton overexpress bone matrix extracellular proteins.
In an attempt to reveal the osteoblast-like phenotype of osteotropic breast
cancer cells, we performed a microarray study on a model of breast cancer bone
metastasis consisting of the MDA-MB-231 human cell line and its variant B02
selected for its high capacity to form bone metastases in vivo. Analysis of B02
cells transcriptional profile revealed that 11 and 9 out of the 50 most up- and
down-regulated mRNAs, respectively, corresponded to genes which expression has
been previously associated with osteoblastic differentiation process. Thus,
osteoblast specific cadherin 11 which mediates the differentiation of mesenchymal
cells into osteoblastic cells is up-regulated in B02. While S100A4, recently
described as a key negative regulator of osteoblast differentiation, is the most
down-regulated gene in B02 cells. RT-PCR and western blotting experiments allowed
the validation of the modulation of several genes of interest. Using
immunohistochemistry, performed on human breast primary tumors and their matched
liver and bone metastases, we were able to confirm that the osteoblast-like
pattern of gene expression observed in our model holds true in vivo. This is the
first report demonstrating a gene-expression pattern corresponding to the
acquisition of an osteomimetic phenotype by bone metastatic breast cancer cells.
PMID- 17028990
TI - Novel triterpenoid 25-hydroxy-3-oxoolean-12-en-28-oic acid induces growth arrest
and apoptosis in breast cancer cells.
AB - 25-Hydroxy-3-oxoolean-12-en-28-oic acid (Amooranin-AMR) is a triterpene acid
isolated from the stem bark of a tropical tree (Amoora rohituka) grown wild in
India. A herbal preparation used for the treatment of cancer by the Ayurvedic
system of medicine contains the stem bark of Amoora rohituka as one of the
ingredients. In this paper, we show that AMR displays a strong inhibitory effect
on survival of human breast carcinoma MDA-468, breast adenocarcinoma MCF-7 cells
compared to breast epithelial MCF-10A control cells. A 50% decrease in cells
(IC50) ranged from 1.8 to 14.6 microM and cell growth was suppressed by arresting
cell cycle at G2 + M phase. AMR effectively induces apoptosis and triggered a
series of effects associated with apoptosis including cleavage of caspase-8, -9,
3, Bid and ER stress in MDA-468 cells and caspase- 8, -9, -6 and Bid in MCF-7
cells, release of cytochrome c from the mitochondria, cleavage of poly (ADP
ribose) polymerase (PARP) and DNA fragmentation with a concomitant upregulation
of p53, Bax and down-regulation of Bcl-2 in MDA-468 cells, but Bax unchanged in
MCF-7 cells. The use of caspase blocking peptides and acridine orange staining
confirmed the involvement of primarily caspase-9 and -3 in MDA-468 cells with
mutated p53 and primarily caspase-8, -9 and -6 in MCF-7 cells expressing wt p53.
We also observed in MCF-7/p53siRNA cells AMR treatment caused reduced expression
of Bcl-2 without affecting levels of Bax similar to MCF-7 cells treated with AMR
and proteolytic activation of Bax in MDA-468 cells. These results suggest that
AMR induces apoptosis in human breast carcinoma cells via caspase activation
pathway and likely it is a p53-independent apoptosis.
PMID- 17028991
TI - Theoretical, developmental & cultural orientations of school-based prevention
programs for preschoolers.
AB - Schools are the primary environment in which to conduct prevention programs for
school-age children. Educators, policy makers, and psychologist argue that
prevention efforts should begin as early as possible to maximize their
effectiveness. Surprisingly, there are relatively few school-based prevention
programs targeted for preschoolers. Given the evidence supporting earlier rather
than later prevention efforts and the fact that many children in the United
States attend preschool programs, more research on the feasibility and
effectiveness of prevention programs administered in preschool environments is
warranted. In this article, we review the existing literature on school-based
prevention programs targeted for preschool children. We examine whether school
based prevention programs are theory driven, developmentally appropriate,
culturally sensitive, and aimed specifically at symptom reduction or behavior
promotion. Based on the findings of this review, our aim is to identify gaps in
the prevention research literature regarding programs for preschoolers and
propose research to address such gaps to create more effective school-based
prevention programs for young children.
PMID- 17028992
TI - Efficacy of a group medication adherence intervention among HIV positive women:
the SMART/EST Women's Project.
AB - This intervention sought to improve overall quality of life and health behavior
in women living with human immunodeficiency virus (HIV). We contrasted the effect
of a group cognitive behavioral stress management expressive supportive therapy
(CBSM+) intervention plus a healthier lifestyles (HL) component with an
individual educational/informational format plus HL on HIV-medication adherence.
Women, n = 237, predominantly African-American and Latina, living with HIV were
recruited from Miami, New York and New Jersey and randomized to group or
individual conditions (ten weekly sessions) plus group or individual HL, i.e.,
four conditions. Women reported relatively high levels of adherence at baseline.
Participants in any of the group conditions increased self-reported adherence and
emotion-focused coping skills in comparison with individual participation. This
study suggests that group interventions may be an important adjunct in increasing
medication adherence for HIV positive women.
PMID- 17028993
TI - Development of a computer-based risk-reduction counseling intervention:
acceptability and preferences among low-income patients at an urban sexually
transmitted infection clinic.
AB - In preparation for the development of an individually tailored, multimedia,
computerized sexually transmitted infection (STI)/HIV-risk reduction intervention
software application for use in publicly funded STI clinics, we conducted a
waiting-room survey among 583 inner-city patients (67% male; 79% African
American; mean age = 30.3) at an STI clinic in Milwaukee, Wisconsin regarding
their computer experience and opinions related to a computerized approach to
HIV/STI-risk reduction counseling. A substantial minority of respondents
indicated they would prefer having either a combined computerized and human
counseling intervention (30%) or preferred a computerized intervention alone
(13%). Perceived benefits of computerized counseling included impartiality of the
response, privacy, accuracy of the information, convenience, and being able to
control the dissemination of information. Perceived disadvantages included lack
of human contact, inability to obtain necessary information, technical problems,
threats to privacy, and failure to take information from a computer seriously.
Despite their limited economic resources, participants reported relatively high
levels of computer experience overall and a willingness to use an individually
tailored computerized risk-reduction counseling approach. We discuss how
participants' responses were used to inform the development of such an
intervention.
PMID- 17028994
TI - A longitudinal study of adolescents with perinatally or transfusion acquired HIV
infection: sexual knowledge, risk reduction self-efficacy and sexual behavior.
AB - As HIV-positive children are surviving to adolescence and beyond, understanding
their HIV knowledge and sexual behavior is critical. Forty HIV+ adolescents/young
adults were interviewed twice, approximately 21 months apart (mean age 16.6 and
18.3 years, respectively). Data on demographics, safer sex knowledge, sexual risk
behaviors, risk reduction self-efficacy, and Tanner stage were collected. Twenty
eight percent of HIV+ youth at Time 1 and 41% at Time 2 reported being sexually
active. HIV transmission/safer sex knowledge was low, increased with age, and
both self-efficacy for and actual condom use was relatively high. Secondary
prevention messages should be incorporated into routine medical settings.
PMID- 17028995
TI - A social cognitive model of health for HIV-positive adults receiving care in
India.
AB - In-depth interviews were conducted with 50 HIV-positive adults (23 women, 27 men)
with access to care at a non-governmental organization in Chennai, India to gain
a broad understanding of how they managed their HIV infection. Using a Social
Cognitive Model of Health, we identified factors within the model's three domains
-Personal, Environmental, and Behavioral--that are applicable to this socio
cultural context. The Personal domain's factors were a positive self-concept,
family-focused goals, and treatment optimism; the Environmental domain comprised
family-based support, treatment availability, access and quality, and HIV stigma
and discrimination; and the Behavior domain's factors were medication adherence
and health habits, sexual behavior, and social relationships and emotional well
being. Significant differences for many of the factors within the three domains
were observed across married men and women, widowed women, unmarried men, and
female sex workers. Implications for an enhanced intervention for HIV-infected
individuals in similar treatment settings are discussed.
PMID- 17028996
TI - The impact of chronic hepatitis C on health-related quality of life in homeless
and marginally housed individuals with HIV.
AB - Although infection with Hepatitis C Virus (HCV) and Human Immunodeficiency Virus
(HIV) frequently co-exist, there has been little research to determine the
effects of HIV/HCV co-infection on health-related quality of life (HRQOL). We
performed a cross-sectional analysis of baseline data from 216 participants
enrolled in a community based study of HIV-infected homeless and marginally
housed individuals, using multivariable linear regression analysis to determine
if co-infection with HCV was independently associated with lower short-form 36
(SF-36) questionnaire scores. We found that individuals with HCV had
significantly lower mean SF-36 scores in the domains of physical functioning,
bodily pain, social functioning and role limitation due to emotional health, and
that HIV/HCV co-infection was independently associated with a lower physical
component score but not a lower mental component score after controlling for
numerous covariates. These results suggest that co-infection with HCV may have an
adverse effect on HRQOL among homeless and marginally housed individuals with
HIV.
PMID- 17028997
TI - Evaluating the risk and attractiveness of romantic partners when confronted with
contradictory cues.
AB - Research shows that people engage in "risky" sex with "safe" partners and in
"safer" sex with "riskier" partners. How is the determination of "risky" or
"safe" status made? Factorial survey methodology was used to randomly construct
descriptions of romantic partners based on attractive and/or risky
characteristics. Respondents evaluated 20 descriptions for attractiveness, health
risk, likelihood of going on a date, likelihood of unprotected sex, and
likelihood of STD/HIV infection. Respondents were most attracted to and perceived
the least risk from attractive descriptions and were least attracted to and
perceived the most risk from the risky descriptions. The differences between the
"conflicting information" descriptions are attributable to a primacy effect:
descriptions that began with attractiveness information but end with risk
information were evaluated more positively than those that began with risk and
ended with attractive information.
PMID- 17028998
TI - Developing a partnership model for cancer screening with community-based
organizations: the ACCESS breast cancer education and outreach project.
AB - There is growing enthusiasm for community-academic partnerships to promote health
in underserved communities. Drawing upon resources available at a comprehensive
cancer center, we developed the ACCESS program to guide community based
organizations through a flexible program planning process. Over a three-year
period, ACCESS partnered with 67 agencies serving various medically underserved
populations. Organizations included hospitals, parishes, senior centers, harm
reduction programs, and recreational facilities. Program outcomes at the
organizational level were quantified in terms of introduction of new cancer
information, referral or screening programs, as well as organizational capacity
building. ACCESS represents a viable model for promoting partnership to transfer
behavioral health programs and adapt interventions for new audiences. Plans to
further evaluate and enhance this model to promote cancer screening efforts are
discussed. We argue that, ultimately, formation and development of community
partnerships need to be understood as a fundamental area of practice that must be
systematically integrated into the mission of major academic medical institutions
in every area of public health.
PMID- 17028999
TI - A comparison of two recorders for obtaining in-flight heart rate data.
AB - : Measurement of mental workload has been widely used for evaluation of aircraft
design, mission analysis and assessment of pilot performance during flight
operations. Heart rate is the psychophysiological measure that has been most
frequently used for this purpose. The risk of interference with flight safety and
pilot performance, as well as the generally constrained access to flights, make
it difficult for researchers to collect in-flight heart rate data. Thus, this
study was carried out to investigate whether small, non-intrusive sports
recorders can be used for in-flight data collection for research purposes. Data
was collected from real and simulated flights with student pilots using the Polar
Team System sports recorder and the Vitaport II, a clinical and research
recording device. Comparison of the data shows that in-flight heart rate data
from the smaller and less intrusive sports recorder have a correlation of.981
with that from the clinical recorder, thus indicating that the sports recorder is
reliable and cost-effective for obtaining heart rate data for many research
situations.
PMID- 17029000
TI - Reducing drug costs at a Veterans Affairs hospital by increasing market-share of
generic fluoxetine.
AB - We previously showed that a multifaceted intervention designed to contain costs
of prescribing selective serotonin reuptake inhibitors (SSRIs) at a Veterans
Affairs hospital resulted in substantial projected savings. Intervention
components included clinician education and pharmacy and computer information
process changes. We now report on effects of altering the intervention to promote
prescribing of generic fluoxetine. Over 30 months, fluoxetine's market-share
increased from 12 to 32% of all SSRIs prescribed. A total of $2,500,000 in cost
avoidance resulted from substituting generic for brand fluoxetine, and $600,000
resulted from increases in market-share of fluoxetine. The results highlight the
robustness and flexibility of the intervention approach.
PMID- 17029001
TI - Genes and the environment in neurodegeneration.
AB - Neurodegenerative diseases are a heterogeneous group of pathologies which
includes complex multifactorial diseases, monogenic disorders and disorders for
which inherited, sporadic and transmissible forms are known. Factors associated
with predisposition and vulnerability to neurodegenerative disorders may be
described usefully within the context of gene-environment interplay. There are
many identified genetic determinants for neurodegeneration, and it is possible to
duplicate many elements of recognized human neurodegenerative disorders in animal
models of the disease. However, there are similarly several identifiable
environmental influences on outcomes of the genetic defects; and the course of a
progressive neurodegenerative disorder can be greatly modified by environmental
elements. In this review we highlight some of the major neurodegenerative
disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic lateral
sclerosis, Huntington's disease, and prion diseases.) and discuss possible links
of gene-environment interplay including, where implicated, mitochondrial genes.
PMID- 17029003
TI - Cell biological and biophysical aspects of lipid-mediated gene delivery.
AB - Cationic lipids are conceptually and methodologically simple tools to deliver
nucleic acids into the cells. Strategies based on cationic lipids are viable
alternatives to viral vectors and are becoming increasingly popular owing to
their minimal toxicity. The first-generation cationic lipids were built around
the quaternary nitrogen primarily for binding and condensing DNA. A large number
of lipids with variations in the hydrophobic and hydrophilic region were
generated with excellent transfection efficiencies in vitro. These cationic
lipids had reduced efficiencies when tested for gene delivery in vivo. Efforts in
the last decade delineated the cell biological basis of the cationic lipid gene
delivery to a significant detail. The application of techniques such as small
angle X-ray spectroscopy (SAXS) and fluorescence microscopy, helped in linking
the physical properties of lipid:DNA complex (lipoplex) with its intracellular
fate. This biological knowledge has been incorporated in the design of the second
generation cationic lipids. Lipid-peptide conjugates (peptoids) are effective
strategies to overcome the various cellular barriers along with the lipoplex
formulations methodologies. In this context, cationic lipid-mediated gene
delivery is considerably benefited by the methodologies of liposome-mediated drug
delivery. Lipid mediated gene delivery has an intrinsic advantage of being a
biomimetic platform on which considerable variations could be built to develop
efficient in vivo gene delivery protocols.
PMID- 17029002
TI - Studies on the critical micellar concentration and phase transitions of
stearoylcarnitine.
AB - The critical micellar concentration (CMC) of stearoylcarnitine was determined at
different pH values at room temperature by fluorescence spectroscopy, monitoring
the spectral changes of 8-anilinonaphthalene-1-sulfonate (ANS). The CMC was found
to vary with pH, increasing from about 10 microM at pH 3.0 to ca. 25 microM at pH
7.0, but decreasing slightly with further increase in pH to approximately 19
microM at pH 10.0. Differential scanning calorimetry (DSC) shows that
stearoylcarnitine dispersed in water at low concentration undergoes a broad
thermotropic phase transition at 44.5 degrees C, with a transition enthalpy of
15.0 kcal/mol. The transition temperature (Tt) shifts to ca. 50.5 degrees C in
the presence of 1 mM EDTA or when the concentration is increased significantly.
The turbidity of aqueous dispersions of stearoylcarnitine was found to be
considerably high at low temperatures, which decreases quite abruptly over a
short temperature range, indicating that a transition occurs from a phase of
large aggregates to one of much smaller aggregates, most likely micelles. The
phase transition temperature was determined as 29.1 degrees C at pH 3.0, which
increased with increasing pH up to a value of 55.3 degrees C at pH 8.6 and
remains nearly constant thereafter up to pH 11.2. The pH dependence of CMC and Tt
suggest that the pKa of the carboxyl group of long chain acylcarnitines shifts to
higher temperatures upon aggregation (micelles or bilayer membranes).
PMID- 17029004
TI - Spectrin organization and dynamics: new insights.
AB - Spectrin is the major constituent protein of the erythrocyte cytoskeleton which
forms a filamentous network on the cytoplasmic face of the membrane by providing
a scaffold for a variety of proteins. In this review, several aspects of spectrin
organization are highlighted, particularly with respect to its ability to bind
hydrophobic ligands and its interaction with membrane surfaces. The
characteristic binding of the fluorescent hydrophobic probes Prodan and pyrene to
spectrin, which allows an estimation of the polarity of the hydrophobic probe
binding site, is illustrated. In addition, the contribution of uniquely localized
and conserved tryptophan residues in the 'spectrin repeats' in these processes is
discussed. A functional implication of the presence of hydrophobic binding sites
in spectrin is its recently discovered chaperone-like activity. Interestingly,
spectrin exhibits residual structural integrity even after denaturation which
could be considered as a hallmark of cytoskeletal proteins. Future research could
provide useful information about the possible role played by spectrin in cellular
physiology in healthy and diseased states.
PMID- 17029005
TI - Stopped-flow kinetic studies of the interaction of bovine folate binding protein
(FBP) and folate.
AB - The kinetics of the interaction of bovine folate binding protein and folate at pH
7.4 and 5.0 were followed by measuring the changes of the intrinsic protein
fluorescence intensity using the stopped-flow technique, which enables the study
of reactions from the millisecond time-range. Our results immediately reject a
simple one-step binding model, which requires a linear dependence of the observed
rate constant on the concentration of the ligand. Thus, we are able to conclude
that at pH 5.0 the interaction occurs in two steps and at pH 7.4 in three steps.
Changes of fluorescence spectra at equilibrium were used to estimate the overall
binding constants. Comparative studies on the binding of folate to human albumin
are also reported.
PMID- 17029006
TI - Modulation of antigenic phenotype in cultured human osteoblast-like cells by
FGFb, TGFbeta1, PDGF-BB, IL-2, IL-1beta, LPS and IFNgamma.
AB - BACKGROUND/AIMS: Recent reports demonstrated that osteoblast-like cells can also
exert activities directly associated with the immune system (cytokine synthesis,
antigen presentation, phagocytosis and stimulation of T lymphocytes). The present
study aimed to analyze the effect of Transforming growth factorbeta1 (TGFbeta1),
Fibroblast growth factor basic (FGFb), Platelet-derived growth factor-BB (PDGF
BB), Interleukin-1beta (IL-1beta), Interleukin-2 (IL-2), Lipopolysaccharide (LPS)
and Interferon-gamma (IFNgamma) on the expression on osteoblast-like cells of
antigens involved in antigen presentation. METHODS: Flow cytometry was used to
investigate whether the growth factors FGFb, TGFbeta1, PDGF-BB, IL-2, IL-1beta,
LPS and IFNgamma modulate the expression on cultured human osteoblast-like cells
of different antigens involved in antigen-presentation and T cell activation.
RESULTS: TGFbeta1 treatment significantly reduced the expression of CD54 and
CD86. IL-1beta treatment significantly enhanced the expression of CD54, CD86 and
HLA-DR. LPS and IFNgamma treatments produced a major increase in CD54, CD80, CD86
and HLA-DR expression. Expression of these antigen-presenting molecules was not
significantly modified by FGFb, PDGF-BB or IL-2 treatment.
PMID- 17029007
TI - A novel agent, methylophiopogonanone B, promotes Rho activation and tubulin
depolymerization.
AB - Cytoskeletal reorganization, including reconstruction of actin fibers and
microtubules, is essential for various biological processes, such as cell
migration, proliferation and dendrite formation. We show here that
methylophiopogonanone B (MOPB) induces cell morphological change via melanocyte
dendrite retraction and stress fiber formation. Since members of the Rho family
of small GTP-binding proteins act as master regulators of dendrite formation and
actin cytoskeletal reorganization, and activated Rho promotes dendrite retraction
and stress fiber formation, we studied the effects of MOPB on the small GTPases
using normal human epidermal melanocytes and HeLa cells. In in vitro binding
assay, MOPB significantly increased GTP-Rho, but not GTP-Rac or GTP-CDC42.
Furthermore, a Rho inhibitor, a Rho kinase inhibitor and a small GTPase inhibitor
each blocked MOPB-induced stress fiber formation. The effect of MOPB on actin
reorganization was blocked in a Rho dominant negative mutant. These results
suggest MOPB acts via the Rho signaling pathway, and it may directly or
indirectly activate Rho. Quantitative Western blot analysis indicated that MOPB
also induced microtubule destabilization and tubulin depolymerization. Thus, MOPB
appears to induce Rho activation, resulting in actin cytoskeletal reorganization,
including dendrite retraction and stress fiber formation.
PMID- 17029009
TI - Feeling strained? Influence of genetic background on depression-related behavior
in mice: a review.
AB - Depression is a growing pandemic in developed societies. The use of inbred mouse
strains in pre-clinical psychiatric research has proven to be a valuable
resource. Firstly, they provide the background for genetic manipulations that aid
in the discovery of molecular pathways that may be involved in major depression.
Further, inbred mouse strains are also being used in the determination of genetic
and environmental influences that may pre-dispose or trigger depression-related
behavior. This review aims to highlight the utility of inbred mouse strains in
depression research, while providing an overview of the current state of research
into behavioral differences between strains in paradigms commonly used in the
field. Neurochemical differences that may underlie strain differences are
examined, and some caveats and cautions associated with the use of inbred strains
are highlighted.
PMID- 17029008
TI - Podophyllum hexandrum modulates gamma radiation-induced immunosuppression in
Balb/c mice: implications in radioprotection.
AB - Aqueous extract of Podophyllum hexandrum (RP-1), which has been reported to
render more than 82% survival against whole body lethal (10 Gy) gamma-irradiation
in mice, was further investigated for its immunomodulatory potential. In this
study, no significant change could be scored in peritoneal macrophages survival
up to 8th day after whole body irradiation. RP-1 treatment (200 mg/kg body
weight, i.p.) alone or 2 h before whole body irradiation enhanced macrophage
survival significantly (p<0.05) as compared to irradiated control mice. In
irradiated animals, there was significant (p<0.01) reduction in splenocyte
survival and proliferation as revealed by 3H-TdR method. RP-1 treatment (200
mg/kg) alone or 2 h before irradiation countered the decrease in survival of
splenocytes and proliferation significantly (p<0.05) as compared to irradiated
control group. Whole body irradiation also significantly (p<0.05) reduced the
population of CD4+ and CD8+ T cells and bone marrow GM-CFU at 24 h and 72 h post
irradiation intervals, respectively, as compared to unirradiated control. RP-1
treatment 2 h before whole body irradiation countered the decrease in CD4+ and
CD8+ T cells populations and CGM-CFU. Nitric oxide free radicals generation was
enhanced significantly (p<0.05) in the supernatant of peritoneal macrophage
cultures exposed to 2 Gy gamma radiation ex vivo in comparison to unirradiated
control, which was reduced by pre-irradiation (-2 h) administration of RP-1.
Whole body irradiation (10 Gy) also reduced the serum titres of IL-3, IL-1 and
various IgG isotypes observed at different post-irradiation time interval. RP-1
treatment alone or before whole body irradiation countered radiation induced
decrease in the titre of IL-1, IL-3 and IgG's in the serum of mice. These
findings indicate immunostimulatory potential of RP-1.
PMID- 17029014
TI - Diffusion MRI in the early diagnosis of malignant glioma.
AB - OBJECTIVE: A subset of patients with malignant glioma comes to medical attention
before their masses show rim enhancement and central necrosis. Tumors in those
cases are frequently located in eloquent areas of the brain. Tissue diagnosis is
limited to stereotactic biopsy providing limited material for accurate grading.
We conducted this study to determine whether imaging characteristics of early
stages of malignant gliomas could aid in timely definitive diagnosis. METHODS: We
retrospectively analyzed patients with newly diagnosed malignant glioma seen at
the Yale Brain Tumor Center between 2002 and 2005. Patients with typical
radiographic presentation were excluded. RESULTS: Of 89 patients, eight meeting
the inclusion criteria were identified. In five patients, patchy or small nodular
enhancing lesions without central necrosis were present within the tumor mass.
Diffusion-weighted imaging (DWI) showed areas of increased signal intensity in
all cases. Apparent diffusion coefficient maps (ADC) revealed low-signal
intensity in corresponding areas. At the time of imaging, biopsy was performed in
seven patients but diagnosis of malignant glioma could only be established prior
to further tumor growth in four cases. CONCLUSIONS: The diagnosis in the early
stages of malignant glioma can be challenging in a subset of cases. Information
obtained through DWI should be incorporated in the clinical decision-making
process. Mass lesions displaying decreased water diffusion indicating high
cellularity, are suggestive of a high-grade glioma. Biopsies are recommended.
However, even when biopsies are inconclusive, a strong suspicion of malignant
glioma should be considered.
PMID- 17029015
TI - Huge lobar intracerebral hemorrhage by glioblastoma multiforme.
PMID- 17029016
TI - Profound effects of the general anesthetic etomidate on oxidative phosphorylation
without effects on their yield.
AB - We investigated the effects of the general anesthetic Etomidate on oxidative
phosphorylation in isolated rat liver mitochondria. The study of each electron
transfer site shows that there is an inhibition: mainly at complex I but also, to
a lesser extent, at complex III. Moreover, with succinate as substrate, the
increase in non-phosphorylating respiration is accompanied by a decrease in
DeltaPsi. However, this effect is not due to classical uncoupling of oxidative
phosphorylation, since ADP addition at high Etomidate concentrations restores the
transmembrane difference of electrical potential. Also, in the same range of
Etomidate concentration, the ATP/O ratio is not significantly affected. In
conclusion, the main effect of Etomidate is to decrease the oxidative
phosphorylation rate without changing yield. The H(+) leak which appears under
non-phosphorylating conditions becomes negligible in physiological conditions.
PMID- 17029017
TI - Gestalt perception and local-global processing in high-functioning autism.
AB - This study examined gestalt perception in high-functioning autism (HFA) and its
relation to tasks indicative of local visual processing. Data on of gestalt
perception, visual illusions (VI), hierarchical letters (HL), Block Design (BD)
and the Embedded Figures Test (EFT) were collected in adult males with HFA,
schizophrenia, depression and normative controls. Individuals with HFA processed
gestalt stimuli less in accord with gestalt laws, particularly regarding the
principle of similarity. Gestalt processing correlated positively with global
processing of the HL. EFT and BD performance correlated negatively with VI
susceptibility in HFA. All clinical groups succumbed less to VI than the
normative sample. Results suggest decreased gestalt perception in HFA, being
associated with a more general local visual processing bias.
PMID- 17029018
TI - Slowing down presentation of facial movements and vocal sounds enhances facial
expression recognition and induces facial-vocal imitation in children with
autism.
AB - This study examined the effects of slowing down presentation of facial
expressions and their corresponding vocal sounds on facial expression recognition
and facial and/or vocal imitation in children with autism. Twelve autistic
children and twenty-four normal control children were presented with emotional
and non-emotional facial expressions on CD-Rom, under audio or silent conditions,
and under dynamic visual conditions (slowly, very slowly, at normal speed) plus a
static control. Overall, children with autism showed lower performance in
expression recognition and more induced facial-vocal imitation than controls. In
the autistic group, facial expression recognition and induced facial-vocal
imitation were significantly enhanced in slow conditions. Findings may give new
perspectives for understanding and intervention for verbal and emotional
perceptive and communicative impairments in autistic populations.
PMID- 17029019
TI - Brief report: perception of body posture--what individuals with autism spectrum
disorder might be missing.
AB - Autism has been associated with atypical face and configural processing, as
indicated by the lack of a face inversion effect (better recognition of upright
than inverted faces). We investigated whether such atypical processing was
restricted to the face or extended to social information found in body postures.
An inversion paradigm compared recognition of upright and inverted faces, body
postures, and houses. Typical adults demonstrated inversion effects for both
faces and body postures, but adults with autism demonstrated only a face
inversion effect. Adults with autism may not have a configural processing deficit
per se, but instead may have strategies for recognizing faces not used for body
postures. Results have implications for therapies employing training in imitation
and body posture perception.
PMID- 17029020
TI - Autism in the Faroe Islands: an epidemiological study.
AB - The Faroe Islands are considered to be a genetic isolate. This population study
of the prevalence of autism sought to identify a representative cohort for future
genetic studies. In 2002 all schools were screened for autism spectrum disorders.
The target population were all children born in 1985 through 1994 and living in
the Faroe Islands on December 31, 2002. Children who screened positive for autism
characteristics were examined using the Diagnostic Interview for Social and
Communication Disorders (DISCO). Of the children aged 8 through 17 years, 0.56%
had childhood autism, Asperger syndrome or atypical autism. The male:female ratio
was just under 6:1. The prevalence of autism in the Faroe Islands was very
similar to that reported from many western countries.
PMID- 17029021
TI - What is the most appropriate energy source for aortic cusp ablation? A comparison
of standard RF, cooled-tip RF and cryothermal ablation.
AB - BACKGROUND: Certain tachycardias can be eliminated by catheter ablation from
within the base of the aortic valve (AV) cusps but the high blood flow and
proximity to the coronary arteries create unique challenges. Standard
radiofrequency (RF) energy, cooled-tip RF energy or cryothermal energy were
compared to determine the optimal ablation modality. MATERIALS AND METHODS:
Experiments were conducted using adult swine or goats (15 animals). Ablation
lesions were placed using either: temperature-controlled RF (4 mm-tip catheter;
60 degrees C/60 s), cooled-tip RF (4 mm-tip catheter with internal saline
circulation at 0.6 ml/s; 40 degrees C/60 s), or cryoablation (6 mm-tip spot
cryocatheter; <-75 degrees C/4 min). Animals were sacrificed 1 h after the last
application and lesions were subject to pathological analysis. RESULTS: Standard
RF and cryoablation created similar depth lesions in the right coronary cusp
(4.2+/-1.3 and 3.4+/-0.5 mm, respectively) but cryoablation was unable to create
any visible lesions in the non-coronary cusp. Cooled tip ablation created larger
ablation lesions in the right coronary cusp (5.25+/-0.5) and fully transmural
left atrial ablation lesions after ablation in the noncoronary cusp. Acute damage
to the cusps was not noted with any ablation modality. Disruption of elastic
fibers in the aortic media was seen after standard and cooled tip radiofrequency
ablation but not cryoablation. CONCLUSION: Cryoablation within the AV cusps
created similar sized lesions to standard RF ablation without evidence of elastic
fibre disruption and may therefore be an appropriate first line ablation
modality. Cooled-tip ablation created larger ablation lesions and therefore may
be required if cryoablation is ineffective.
PMID- 17029022
TI - Bone morphogenetic proteins and their antagonists.
AB - Skeletal homeostasis is determined by systemic hormones and local factors. Bone
morphogenetic proteins (BMPs) are unique because they induce the commitment of
mesenchymal cells toward cells of the osteoblastic lineage and also enhance the
differentiated function of the osteoblast. BMP activities in bone are mediated
through binding to specific cell surface receptors and through interactions with
other growth factors. BMPs are required for skeletal development and maintenance
of adult bone homeostasis, and play a role in fracture healing. BMPs signal by
activating the mothers against decapentaplegic (Smad) and mitogen activated
protein kinase (MAPK) pathways, and their actions are tempered by intracellular
and extracellular proteins. The BMP antagonists block BMP signal transduction at
multiple levels including pseudoreceptor, inhibitory intracellular binding
proteins, and factors that induce BMP ubiquitination. A large number of
extracellular proteins that bind BMPs and prevent their binding to signaling
receptors have emerged. The extracellular antagonists are differentially
expressed in cartilage and bone tissue and exhibit BMP antagonistic as well as
additional activities. Both intracellular and extracellular antagonists are
regulated by BMPs, indicating the existence of local feedback mechanisms to
modulate BMP cellular activities.
PMID- 17029024
TI - Price vs. quantity in health insurance reimbursement.
AB - While "integrated" systems regulate the quantity of health services,
"Bismarckian" systems regulate their price. This paper compares the consumers'
allocations implemented within the two reimbursement systems. In the model,
illness has a negative impact on labor productivity while public insurance is
financed through income tax. Consumers have private information with respect to a
parameter which can be interpreted as heterogeneity either in intensity of their
preferences for treatment or in the type of illness. The social planner may be
constrained to adopt uniform insurance plans, or may be free to choose self
selecting plans. The analysis of uniform plans shows that Bismarckian systems
dominate integrated systems from the social welfare point of view; whereas the
opposite ranking holds with self-selecting plans.
PMID- 17029025
TI - Reconceptualizing the case management relationship in intensive treatment: a
study of staff perceptions and experiences.
AB - The helping relationship or alliance is theorized to be an important process
variable in case management services for people with serious mental illness.
Previous studies of the case management relationship borrow concepts and measures
from psychotherapy research and therefore may overlook important differences in
tasks, settings, and clinical roles across settings. A study of client-provider
relationships as perceived by case managers, based on a qualitative study of two
intensive case management (ICM) teams, is presented. The findings, which
delineate positive and negative experiential elements, may be used to improve
measurement of the case management relationship in future research.
PMID- 17029027
TI - Consultation-based academic interventions for children with ADHD: effects on
reading and mathematics achievement.
AB - The purpose of this investigation was to evaluate the relative efficacy of two
consultation-based models for designing academic interventions to enhance the
educational functioning of children with attention-deficit/hyperactivity disorder
(ADHD). Children (N=167) meeting DSM-IV criteria for ADHD were randomly assigned
to one of two consultation groups: Individualized Academic Intervention (IAI;
interventions designed using a data-based decision-making model that involved
ongoing feedback to teachers) and Generic Academic Intervention (GAI;
interventions designed based on consultant-teacher collaboration, representing
"consultation as usual"). Teachers implemented academic interventions over 15
months. Academic outcomes (e.g., standardized achievement test, and teacher
ratings of academic skills) were assessed on four occasions (baseline, 3 months,
12 months, 15 months). Hierarchical linear modeling analyses indicated
significant positive growth for 8 of the 14 dependent variables; however,
trajectories did not differ significantly across consultation groups.
Interventions in the IAI group were delivered with significantly greater
integrity; however, groups did not differ with respect to teacher ratings of
treatment acceptability. The results of this study provide partial support for
the effectiveness of consultation-based academic interventions in enhancing
educational functioning in children with ADHD; however, the relative advantages
of an individualized model over "consultation as usual" have yet to be
established.
PMID- 17029026
TI - Attention processes in children with movement difficulties, reading difficulties
or both.
AB - Reading difficulties (RD) and movement difficulties (MD) co-occur more often in
clinical populations than expected for independent disorders. In this study, we
investigated the pattern of association between attentional processes, RD and MD
in a population of 9 year old school children. Children were screened to identify
index groups with RD, MD or both, plus a control group. These groups were then
tested on a battery of cognitive attention assessments (TEA-Ch). Results
confirmed that the occurrence of RD and MD was greater than would be predicted
for independent disorders. Additionally, children with MD, whether or not
combined with RD, had poor performance on all attention measures when compared
with typically developing children. Children with RD only, were no poorer on
measures of attention than typical children. The results are discussed with
respect to approaches proposed to account for the co-occurrence of disorders.
PMID- 17029028
TI - Intratumoral cytokines/chemokines/growth factors and tumor infiltrating dendritic
cells: friends or enemies?
AB - The tumor microenvironment consists of a variable combination of tumor cells,
stromal fibroblasts, endothelial cells and infiltrating leukocytes, such as
macrophages, T lymphocytes, and dendritic cells. A variety of cytokines,
chemokines and growth factors are produced in the local tumor environment by
different cells accounting for a complex cell interaction and regulation of
differentiation, activation, function and survival of multiple cell types. The
interaction between cytokines, chemokines, growth factors and their receptors
forms a comprehensive network at the tumor site, which is primary responsible for
overall tumor progression and spreading or induction of antitumor immune
responses and tumor rejection. Although the general thought is that dendritic
cells are among the first cells migrating to the tumor site and recognizing tumor
cells for the induction of specific antitumor immunity, the clinical relevance of
dendritic cells at the site of the tumor remains a matter of debate regarding
their role in the generation of successful antitumor immune responses in human
cancers. While several lines of evidence suggest that intratumoral dendritic
cells play an important role in antitumor immune responses, understanding the
mechanisms of dendritic cell/tumor cell interaction and modulation of activity
and function of different dendritic cell subtypes at the tumor site is
incomplete. This review is limited to discussing the role of intratumoral
cytokine network in the understanding immunobiology of tumor-associated dendritic
cells, which seems to possess different regulatory functions at the tumor site.
PMID- 17029029
TI - Advances in methods for assessing tumor hypoxia in vivo: implications for
treatment planning.
AB - Tumor hypoxia and its downstream effects have remained of considerable interest
for decades due to its negative impact on response to various cancer therapies
and promotion of metastasis. Diagnosing hypoxia non-invasively can provide a
significant advancement in cancer treatment and is the dire necessity for
implementing specific targeted therapies now emerging to treat different aspects
of cancer. A variety of techniques are being proposed to do so. However, none of
them has yet been established in the clinical arena. This review summarizes the
methods currently available to assess tumor hypoxia in vivo and their respective
advantages and shortcomings. It also points out the impedances that need to be
overcome to establish any particular method in the clinic, along with a broad
overview of requirements for further advancement in this sphere of cancer
research.
PMID- 17029030
TI - The paradox of pro-inflammatory cytokines in cancer.
AB - Cytokines such as IL-1 and TNF are primarily pro-inflammatory. The inflammation
induced by these cytokines is reflected in the type of genes they induce. In the
pathogenesis of carcinogenesis as well as tumor growth and spread, cytokines such
as IL-1 and TNF induce chemokines that attract neutrophils. Neutrophils are key
players in the production of reactive oxygen species and carcinogenesis. Another
aspect of pro-inflammatory cytokines is the induction of adhesion molecules and
metalloproteinases, both of which provide mechanisms for tumor invasion. Blocking
cytokines, however, will reduce tumor growth and spread if administered at
sufficient concentrations and will require parenteral therapy. However, blocking
cytokines will not kill tumor cells nor prevent carcinogenesis. Blocking
cytokines is best as an adjunct therapy together with tumorocidal drugs.
PMID- 17029031
TI - Dynamics of increased neutrophil adhesion to ICAM-1 after contacting immobilized
IL-8.
AB - Changing affinity of beta(2)-integrins on neutrophils for their ligands on
endothelium is a critical, regulated step in the inflammatory response. In this
report, the dynamics of the neutrophil response to the inflammatory chemokine
interleukin-8 (IL-8) is examined. Human IL-8 was immobilized on beads and brought
into contact with neutrophils selected from whole blood samples. Resulting
changes in cellular adhesion were assessed by measuring the adhesion frequency
between a human neutrophil and a bead coated with the endothelial ligand ICAM-1
(intercellular adhesion molecule-1). Cells engulfed the IL-8 coated beads within
a few tens of seconds, and most of the cells exhibited an increase in adhesion to
ICAM-1 after approximately 5 to 10 min of contact with IL-8 at room temperature
(3 to 5 min at 37 degrees C). Neither monocyte chemotactic protein-1 (MCP-1) nor
anti-CD45-coated beads caused any changes in adhesion to ICAM-1. IL-8 induced
adhesion was blocked by antibody against CD18. At lower surface density of
chemokine, approximately 20% of IL-8 coated beads adhered but were not engulfed
by the cells, although the increase in adhesion for ICAM-1 was still effected.
Heterogeneity in the cellular response and variability between donors was also
noted.
PMID- 17029032
TI - Knee-loading modality drives molecular transport in mouse femur.
AB - Mechanical loading is well known to stimulate bone remodeling. Load-driven
interstitial fluid flow and molecular transport have been postulated to play a
role in the enhancement of bone formation. In order to evaluate load-driven
molecular transport in a lacunocanalicular network, we conducted fluorescence
recovery after photobleaching (FRAP) experiments using lacunae stained with
uranine (376 Da). Loads were applied to a mouse femur ex vivo with a novel knee
loading modality, where the distal epiphysis was loaded with a sinusoidal force
at 2 Hz. The lacunae in the diaphysis located 25% (approximately 4 mm) proximal
to the loading site were photobleached and sequentially imaged, and a time
constant for fluorescence recovery was determined both with and without knee
loading. The time constant was estimated as the period to recover 63% of
fluorescent intensity using a best-fit exponential curve. The results reveal that
the applied loads shortened the time constant from 33 +/- 9 s with non-loading
control to 25 +/- 11 s with knee loading (p = 0.0014). The strain in the
measurement site was <100 microstain along the femoral midshaft, which was an
order of magnitude smaller than the minimum effective strain threshold for bone
remodeling. Taken together, the current study supports the notion that molecular
transport in cortical bone is enhanced by the loads applied to the epiphysis
without inducing significant in situ strain in the diaphysis.
PMID- 17029033
TI - The brain computer interface using flash visual evoked potential and independent
component analysis.
AB - In this study flashing stimuli, such as digits or letters, are displayed on a LCD
screen to induce flash visual evoked potentials (FVEPs). The aim of the proposed
interface is to generate desired strings while one stares at target stimulus one
after one. To effectively extract visually-induced neural activities with
superior signal-to-noise ratio, independent component analysis (ICA) is employed
to decompose the measured EEG and task-related components are subsequently
selected for data reconstruction. In addition, all the flickering sequences are
designed to be mutually independent in order to remove the contamination induced
by surrounding non-target stimuli from the ICA-recovered signals. Since FVEPs are
time-locked and phase-locked to flash onsets of gazed stimulus, segmented epochs
from ICA-recovered signals based on flash onsets of gazed stimulus will be
sharpen after averaging whereas those based on flash onsets of non-gazed stimuli
will be suppressed after averaging. The stimulus inducing the largest averaged
FVEPs is identified as the gazed target and corresponding digit or letter is sent
out. Five subjects were asked to gaze at each stimulus. The mean detection
accuracy resulted from averaging 15 epochs was 99.7%. Another experiment was to
generate a specified string '0287513694E'. The mean accuracy and information
transfer rates were 83% and 23.06 bits/min, respectively.
PMID- 17029034
TI - The role of pulse pressure in the hemodynamic control of hypertension: exploring
the link to cardiovascular remodeling.
AB - OBJECTIVE: To correlate the values in the basic blood pressure groups presented
in the JNC 7th with the computed values of the Noninvasive Hemodynamic Analyzer
(NHA) and to demonstrate the pathophysiological alterations by three proportional
hypertensive models. DESIGN: Hemodynamic values of each of the blood pressure
groups presented in the JNC 7th are tabulated for men between 20 and 50 years of
age with particular interest in Pulse Pressure. PATIENTS: Idealized patients were
used in the three groups of the proportional hypertensive models. VALIDITY:
Previous studies demonstrated that the Bias, Precision, and Accuracy of Cardiac
Output measurement, compared to Thermodilution technique, resulted in
statistically acceptable clinical values. CONCLUSION: This research has
successfully demonstrated, with the use of the NHA, the leading role of Pulse
Pressure in normal and hypertensive patients. We are convinced that this
technique can be used as an economical and time-saving alternative screening tool
in clinical medicine.
PMID- 17029040
TI - The epigenetic alteration of synovial cell gene expression in rheumatoid
arthritis and the roles of nuclear factor kappaB and Notch signaling pathways.
AB - Rheumatoid arthritis (RA) is a complex process of chronic and progressive
inflammation associated with activation of numerous signaling molecules and
transcription factors and hyperproliferation of synoviocytes of the affected
joints, although the greater part of its pathophysiological process is explained
by activation of nuclear factor kappaB (NF-kappaB). For example, the self
perpetuating nature of the rheumatoid inflammation is ascribable to
overexpression of the proinflammatory cytokines tumor necrosis factor alpha and
interleukin-1beta, known to elicit the activation cascade for NF-kappaB and
activator protein-1 that are responsible for transcriptional induction of these
cytokines among other target genes, which conform a positive feedback loop for
continuation and expansion of the inflammatory responses. In addition,
comparative gene expression profile analyses have revealed activation of a number
of genes that explain the "transformed-like" phenotype of synoviocytes. Among the
genes expressed in rheumatoid synoviocytes upon inflammatory stimuli, induction
of gene expression of Notch proteins and its ligand have been found. Possible
roles of Notch signaling in RA synoviocytes are discussed.
PMID- 17029041
TI - Naturopathic management of rheumatoid arthritis.
AB - Complementary and alternative medicines (CAM) are widely used by those with pain
and/or musculoskeletal problems, and previous research has shown that high
proportions of individuals with rheumatoid arthritis have used these therapies.
One of the largest CAM modalities is that of naturopathy, which combines
nutritional, herbal, and other complementary practices to treat such conditions.
In this review, evidence is examined in relation to those factors which
naturopaths believe are significant contributors to rheumatoid arthritis, and are
hence the main focus of therapeutic management. These factors include food
allergy, increased gut permeability, increased circulating immune complexes,
excessive inflammatory processes, and increased oxidative stress. Naturopathic
treatment attempts to alleviate symptoms by altering these factors through
dietary modification, manipulation of dietary fats, and use of antioxidants and
proteolytic enzymes. An understanding of the rationale for these treatments and
evaluation of the evidence from their use in clinical settings will assist with
the integration of complementary and conventional practices in the treatment of
rheumatoid arthritis.
PMID- 17029042
TI - Prediction of and prophylaxis against Pneumocystis pneumonia in patients with
connective tissue diseases undergoing medium- or high-dose corticosteroid
therapy.
AB - We performed a retrospective analysis to establish a statistical model for the
prediction of Pneumocystis pneumonia (PCP) in patients with connective tissue
diseases (CTD) undergoing medium- or high-dose corticosteroid therapy, to
identify independent risk factors for PCP and to evaluate the efficacy of the
prophylactic use of trimethoprim-sulfamethoxazole (TMP/SMX) against PCP. One
hundred and twenty-four patients who were receiving the equivalent of or more
than 30 mg/day of prednisol-one (PSL) were classified into two groups according
to the presence (prophylaxis group, n = 46) or absence (nonprophylaxis group, n =
78) of prophylactic TMP/SMX. We developed a statistical model that was suitable
for predicting the development of PCP using a logistic regression analysis. The
initial steroid dosage, decreased peripheral blood lymphocyte counts at 2 weeks
(<500/microl), and usage of immunosuppressant during 2 weeks after the
institution of PSL (>or=30 mg/day) were found to independently contribute to the
development of PCP. Finally, in the patient group with a defined risk for PCP, a
significant prophylactic effect of TMP/SMX was demonstrated. We recommend the
prophylactic use of TMP/SMX for patients with CTD undergoing medium- or high-dose
corticosteroid therapy who are determined to have a high risk of developing PCP.
PMID- 17029043
TI - Infliximab acts directly on human osteoclast precursors and enhances osteoclast
formation induced by receptor activator of nuclear factor kappaB ligand in vitro.
AB - Infliximab is known to protect against the development of joint destruction. In
the present study, we sought to determine whether Infliximab acts directly on
human osteoclast precursors and influences monocyte-osteoclast differentiation
induced by receptor activator of nuclear factor kappaB ligand (RANKL) in vitro.
Peripheral blood mononuclear cells (PBMCs) isolated from rheumatoid arthritis
(RA) patients and normal controls were cultured in the presence of RANKL and
macrophage colony stimulating factor. Infliximab, antihuman tumor necrosis factor
alpha (TNFalpha), antihuman TNF soluble receptor p55 (TNFR p55), and antihuman
TNF soluble receptor p75 (TNFR p75) antibodies were added. Osteoclast formation
was determined by assessing the number of tartrate-resistant acid phosphatase
(TRAP) staining cells and the extent of lacunar resorption. Addition of
Infliximab resulted in a marked increase in the number of TRAP-positive
multinucleated cells (TRAP(+) MNCs) and in the extent of lacunar resorption
compared with the control cultures. Antihuman TNFalpha antibody showed the same
effect; however, the addition of neither TNFR p55 nor TNFR p75 antibody affected
the extent of TRAP(+) MNCs and lacunar resorption. Our results suggest that
infliximab acts directly on early osteoclast precursors, and stimulates
osteoclast formation and lacunar resorption induced by RANKL in vitro.
PMID- 17029036
TI - Gender-dependent modulation of brain monoamines and anxiety-like behaviors in
mice with genetic serotonin transporter and BDNF deficiencies.
AB - 1. Brain-derived neurotrophic factor (BDNF) supports serotonergic neuronal
development and our recent study found that heterozygous mice lacking one BDNF
gene allele interbred with male serotonin transporter (SERT) knockout mice had
greater reductions in brain tissue serotonin concentrations, greater increases in
anxiety-like behaviors and greater ACTH responses to stress than found in the
SERT knockout mice alone. 2. We investigated here whether there might be gender
differences in these consequences of combined SERT and BDNF deficiencies by
extending the original studies to female mice, and also to an examination of the
effects of ovariectomy and tamoxifen in these female mice, and of 21-day 17-beta
estradiol implantation to male mice. 3. We found that unlike the male SERTxBDNF
deficient mice, female SERTxBDNF mice appeared protected by their gender in
having significantly lesser reductions in serotonin concentrations in
hypothalamus and other brain regions than males, relative to controls. Likewise,
in the elevated plus maze, female SERTxBDNF-deficient mice demonstrated no
increases in the anxiety-like behaviors previously found in males. 4.
Furthermore, female SERTxBDNF mice did not manifest the approximately 40%
reduction in the expression of TrkB receptors or the approximately 30% reductions
in dopamine and its metabolites that male SERTxBDNF did. After estradiol
implantation in male SERTxBDNF mice, hypothalamic serotonin was significantly
increased compared to vehicle-implanted mice. These findings support the
hypothesis that estrogen may enhance BDNF function via its TrkB receptor, leading
to alterations in the serotonin circuits, which modulate anxiety-like behaviors.
5. This double-mutant mouse model contributes to the knowledge base that will
help in understanding genexgenexgender interactions in studies of SERT and BDNF
gene polymorphisms in human genetic diseases such as anxiety disorders and
depression.
PMID- 17029044
TI - Malnutrition and disease progression in patients with rheumatoid arthritis.
AB - To examine the changes in nutritional status during the progression of rheumatoid
arthritis (RA), we studied anthropometric and biochemical variables in 97
Japanese patients with RA. Anthropometric data included body mass index (BMI),
triceps skinfold thickness (TSF), and arm muscle area (AMA). Levels of albumin
and cholesterol in serum, and lymphocyte count were studied as biochemical
variables. The prevalence of malnutrition defined as hypoalbuminemia less than
3.4 g/dl was 24.7%, similar to the reports in other countries. Analysis of the
data according to disease stage showed that malnutrition in RA was characterized
by a progressive reduction in body protein. Body mass index and TSF were
increased in patients with stage 1 disease, whereas serum albumin and AMA were
within normal range. Stage 2 patients had normal BMI with decreased body protein,
albumin, and AMA. Progression to stages 3 and 4 was associated with a stepwise
decrease in AMA; serum albumin and BMI remained in the same range as stage 2.
Albumin values and AMA were significantly lower in patients with poor functional
class and high C-reactive protein. The characteristic progression of malnutrition
in RA is attributed to excessive protein catabolism evoked by inflammatory
cytokines and by disuse atrophy due to functional impairment.
PMID- 17029045
TI - Transforming growth factor beta stimulates rheumatoid synovial fibroblasts via
the type II receptor.
AB - Transforming growth factor (TGF)-beta regulates the function of fibroblasts, and
has been shown to have a role in the pathogenesis of rheumatoid arthritis (RA)
because several studies have demonstrated the presence of TGF-beta in the
synovial tissue and synovial fluids of RA patients. In this study, we examined
the expression of TGF-beta receptors in synovial fibroblasts of patients with RA
and demonstrated the significance in functional responses of synovial fibroblasts
to TGF-beta in this disorder. Transforming growth factor beta1 stimulated the
expression of connective tissue growth factor (CTGF) in fibroblasts of patients
with RA more than in those of patients with osteoarthritis (OA). Transforming
growth factor beta1 induced the chemotactic migration of RA synovial fibroblasts
and inhibited their proliferation significantly more than OA synovial
fibroblasts. Both RA and OA synovial fibroblasts expressed detectable amounts of
TGF-beta receptor type II mRNA, but the expression was higher in RA patients than
in OA patients, as assessed by reverse transcriptase-polymerase chain reaction.
There was no significant difference in the expression of TGF-beta receptor type I
or type III in synovial fibroblasts between RA and OA patients. These results
indicate that synovial fibroblasts of RA patients express the increased TGF-beta
receptor type II, which is associated with altered responses to TGF-beta observed
in CTGF expression, chemotaxis, and proliferation of RA synovial fibroblasts, and
may have an important role in the pathogenesis of RA.
PMID- 17029046
TI - A case of nodular-type muscular sarcoidosis: findings of imaging, histopathology,
and polymerase chain reaction.
AB - We report a case of nodular-type muscular sarcoidosis with no systemic symptoms.
Thallium-201 scintigraphy showed intense uptake in the muscular lesion mimicking
malignant soft tissue tumor. Magnetic resonance imaging (MRI) demonstrated
characteristic signal patterns of peripheral high intensity with central low
intensity ("three stripes" pattern). Microscopy revealed sarcoid granuloma with
typical histopathological characteristics. Propionibacterium acnes was detected
on polymerase chain reaction analysis of the excised tissue.
PMID- 17029047
TI - Rheumatoid arthritis complicated with myeloperoxidase antineutrophil cytoplasmic
antibody (MPO-ANCA)-associated vasculitis: a case report.
AB - This article describes a patient with rheumatoid arthritis (RA) with crescentic
glomerulonephritis (CrGN) associated with myeloperoxidase-antineutrophil
cytoplasmic antibodies (MPO-ANCA), who responded well to methotrexate (MTX). A 48
year-old woman with a 4-year history of RA was admitted with fever and elevated C
reactive protein. On laboratory evaluation, her level of MPO-ANCA was 422 EU, and
urinalysis revealed proteinuria and hematuria. Because she was also suffering
from episcleritis, vasculitis was considered. A renal biopsy was performed, which
revealed necrotizing CrGN. We diagnosed RA complicated with MPO-ANCA-associated
vasculitis. We considered treatment with high-dose oral prednisolone for
vasculitis, but the patient refused this treatment. We started MTX at a dose of 8
mg/week for RA from the time of admission, and the patient responded immediately.
Biochemical parameters, including C-reactive protein, erythrocyte sedimentation
rate, rheumatoid factor, and MPO-ANCA, improved. Seven months later, MPO-ANCA had
decreased to 46 EU. In clinical studies, few patients have been reported with RA
complicated with ANCA-associated CrGN. This case differs from previous cases in
the treatment given. No high-dose steroid with intensive immunosuppression or
plasma exchange was required.
PMID- 17029048
TI - Repeated postoperative laryngeal obstruction due to bilateral cricoarytenoid
joint involvement in rheumatoid arthritis.
AB - A 61-year-old woman with a 40-year history of severe rheumatoid arthritis
developed postoperative laryngeal obstruction twice; the first episode occurred
just after surgery for cervical myelopathy and the second episode occurred 3
weeks after surgery when physiotherapy activity increased. A flexible laryngeal
endoscopy demonstrated that abduction of the bilateral vocal cords was severely
disturbed at the paramedian position, suggesting a diagnosis of cricoarytenoid
arthritis. Early administration of corticosteroids was successful.
PMID- 17029049
TI - Concurrent occurrence of allergic granulomatous angiitis and temporal arteritis:
a case report and review of the literature.
AB - Allergic granulomatous angiitis (AGA) is a disease entity that was first
distinguished from classical polyarteritis nodosa by Churg and Strauss in 1951,
and is characterized by the clinical features of allergic rhinitis or bronchial
asthma, eosinophilia, and vasculitis. Allergic granulomatous angiitis has been
described to mainly involve small vessels. We herein describe a case of Churg
Strauss syndrome which demonstrated the clinical and laboratory findings
supporting a diagnosis of AGA and was also associated with the clinical and
pathological findings for temporal arteritis, which was characterized by
eosinophil infiltration and granuloma formation of the temporal artery (middle
sized vessel).
PMID- 17029050
TI - Catastrophic transverse myelitis in a patient with systemic lupus erythematosus.
AB - A 24-year-old Japanese woman was admitted to our hospital suffering from high
fever and progressive paralysis in both legs. Magnetic resonance imaging of the
spinal cord showed high-intensity signals from C5 to Th4 and from Th7 to L1 on T2
weighted images. The patient was diagnosed as having acute transverse myelitis
trade mark, which was a complication of systemic lupus erythematosus based on the
serological findings. Despite aggressive immunosuppressive treatments including
corticosteroid pulse therapy, plasmapheresis, and intravenous cyclophosphamide,
the paralysis of her lower extremities did not improve. In the catastrophic type
of lupus-associated TM, which develops extensively and longitudinally along the
spinal cord, the prognosis still seems to be poor despite intensive treatments.
PMID- 17029051
TI - Normotensive scleroderma renal crisis with diffuse alveolar damage after
corticosteroid therapy.
AB - A 68-year-old woman with systemic sclerosis developed acute respiratory failure
due to diffuse alveolar hemorrhage and normotensive scleroderma renal crisis
(SRC) shortly after the initiation of corticosteroid therapy. Treatment with
angiotensin-converting enzyme inhibitor and plasmapheresis had failed in this
patient. Autopsy showed diffuse alveolar damage and thrombotic micro-angiopathy.
The sequence of events in this patient clarifies the pathologic process of
normotensive SRC, and suggests a causative role of corticosteroid therapy and
normotensive SRC.
PMID- 17029052
TI - Bilateral total knee arthroplasty after spontaneous osseous ankylosis in
rheumatoid arthritis.
AB - Total knee arthroplasty (TKA) was carried out on both knee joints for spontaneous
bony ankylosis due to rheumatoid arthritis (RA). Preoperative fixation angles
were 40 degrees . First, the peroneal nerve was released prior to TKA. Quadriceps
snip was performed to evert the patella laterally. Bilateral TKAs were carried
out using a stabilized prosthesis. The results showed full extension to 70
degrees flexion at 3 years after the surgery. Absence of pain, maintenance of
stability, and walking ability were achieved, without any significant
complication. Total knee arthroplasty following takedown of a spontaneous
ankylosed knee is an effective procedure under appropriate knee conditions.
PMID- 17029053
TI - Sensorimotor polyneuropathy as an initial clinical manifestation of sarcoidosis.
AB - A 45 year-old Japanese woman developed numbness and tingling of both hands and
feet. Electrophysiological examination revealed sensorimotor polyneuropathy. She
was diagnosed as suffering from sarcoidosis on the basis of the pathological
findings from dermal biopsy. Steroid therapy effectively improved the clinical
symptoms. Although sarcoid neuropathy is rare, this case suggests sensorimotor
polyneuropathy is an important symptom of sarcoidosis and can represent the
initial clinical manifestation of the disease.
PMID- 17029054
TI - Bronchiolar disease associated with gold compounds administration in a patient
with rheumatoid arthritis.
AB - We report the case of a female patient with rheumatoid arthritis (RA) treated
with gold sodium thiomalate and auranofin who developed bronchopulmonary
involvement. Chest X-ray films showed diffuse mottled infiltrates and bronchial
wall thickness in both lungs. Computed tomography revealed opacities along the
thickening of the bronchovascular bundles. The pathologic findings were
indistinguishable from those of diffuse panbronchiolitis. After discontinuation
of gold compounds and initiation of steroid administration, her subjective
symptoms immediately subsided. We conclude that our patient, who had suffered
from chronic sinusitis and had a predisposition to bronchiolar disease, had
bronchiolar disease induced by gold compounds.
PMID- 17029055
TI - Treatment of early rheumatoid arthritis.
AB - Recent advances in the understanding of the pathophysiology, aggressive
treatment, and early detection of rheumatoid arthritis (RA) have changed the
clinical, pathologic, and functional outcomes in patients with RA. Early
aggressive treatment of RA has now become the norm in clinical practice rather
than the use of the traditional pyramid approach of the last half of the
twentieth century. Early treatment with monotherapy of traditional disease
modifying antirheumatic drugs (DMARDs) or biologics, combination traditional
DMARD therapy and, especially, combination of biologic therapy and methotrexate,
have revolutionized the treatment of RA, producing significant improvement in
clinical, radiographic, and functional outcomes not seen previously. For the
individual patient, we still cannot determine which medication or combination of
medications will give the most complete response. There have been a number of
recent, well-designed clinical trials that have tried to answer this question.
Herein we review the evidence-based medicine that addresses these issues.
PMID- 17029056
TI - Glucocorticoid-induced osteoporosis: skeletal manifestations of glucocorticoid
use and 2004 Japanese Society for Bone and Mineral Research-proposed guidelines
for its management.
AB - Glucocorticoid (GC) is widely used to treat a variety of inflammatory and
allergic diseases, and about 0.9% of the adult population in Japan (approximately
one million people) are known to take oral GC at any given time. GC causes a
number of significant side effects, among which are skeletal manifestations such
as osteoporosis and degenerative bone fracture, maor complications of GC therapy.
Although the population of GC-induced osteoporosis patients is estimated to be
approximately one-fifth of patients with primary osteoporosis, few physicians are
aware of the increased risk of fracture caused of GC, and there is inadequate
information concerning the effetiveness of prevention and treatment of GC-induced
osteoporosis. Recently, mechanisms of GC-induced osteoporosis have been
clarified, and treatment strategies have been developed. Accordingly, the 2004
Japanese Society for Bone and Mineral Research (JSBMR)-proposed guidelines for
the management and treatment of GC-induced osteoporosis have been developed based
on the results of a longitudinal study by subcommittee members and the results of
an analysis of patients collected by the Subcommittee to Study Diagnostic
Criteria for Corticosteroid-induced Osteoporosis, together with evidence obtained
overseas and in Japan. The present guideline is prepared for clinical practice.
PMID- 17029057
TI - Locking compression plating: a new solution for fractures in rheumatoid patients.
AB - Osteoporosis is a well-known phenomenon in rheumatoid arthritis (RA) that is
characterized by marked loss of peripheral bone. It was found that the frequency
of osteoporosis in RA can be increased significantly compared with the reference
population, which implies a higher risk of fracture in this group of patients.
Osteoporosis makes the treatment of fracture in RA patients more challenging,
including the difficulty of fracture fixation, delayed union, secondary loss of
reduction, and fixation failure. The locking compression plate was designed using
the concept of "internal fixator," which provides a new solution for the fixation
of osteoporotic fractures. The fixed angle between the screw and the plate
increases the pull-out strength of the system, so the stability of the fixation
no longer depends totally on the quality of the bone. The other benefits of this
system include the fact that no accurate contouring is required, it protects the
local blood supply, and it supports minimally invasive plate osteosynthesis.
PMID- 17029058
TI - Leflunomide-related lung injury in patients with rheumatoid arthritis: imaging
features.
AB - Imaging findings of 26 cases of leflunomide (Arava)-related acute lung injury
were analyzed. Thirteen cases had pre-existing interstitial pulmonary disease on
chest X-ray or computed tomography. The main features of clinically determined
leflunomide-induced acute lung injury were similar to those caused by other
drugs: diffuse or widespread patchy ground-glass opacities and/or consolidation,
frequently accompanied by septal thickening and intralobular reticular opacities.
We categorized these findings into four patterns: diffuse alveolar damage (DAD),
acute eosinophilic pneumonia, hyperreaction, and cryptogenic organizing
pneumonia. The DAD group had a higher mortality rate, but statistically not a
significant one. It is impossible to exclude infectious disease such as
pneumocystis carinii pneumonia based on imaging findings, and detailed
correlation of imaging findings with clinical and laboratory findings is
essential in order to make a correct diagnosis.
PMID- 17029060
TI - Radiographic comparative evaluation of the Sauve-Kapandji procedure and the
Darrach procedure for rheumatoid wrist reconstruction.
AB - For surgical treatment of rheumatoid wrists, we have routinely selected the Sauve
Kapandji (S-K) procedure or the Darrach procedure based on predetermined
indications. In this study, we conducted a retrospective radiographic comparative
evaluation of the changes in the carpus after the two procedures. The S-K group
and the Darrach group each consisted of 13 wrists of 10 patients (all women). The
indications for the Darrach procedure were the presence of radiolunate fusion,
radial shelf formation, and old age. The carpal height ratio (CHR) and the
ulnocarpal distance ratio (UCDR) were determined on wrist radiograms obtained
before operation and at the final follow-up. The mean follow-up period was 4
years. Fisher's test was used to analyze the differences between the two groups.
Both groups showed a decrease in mean CHR and an increase in mean UCDR at the
final follow-up compared to the values before the operation, and there were no
statistically significant differences. Furthermore, in the Darrach group, no
significant differences in changes of the carpus were observed between patients
with or without a radial shelf. We concluded that the present results do not
support the superiority of the S-K method over the Darrach procedure for
rheumatoid wrist reconstruction based on a radiographic evaluation.
PMID- 17029059
TI - Analysis for the major contributor of collagenase to the primary cleavage of type
II collagens in cartilage degradation.
AB - Degradation of type II collagen is a central process in cartilage destruction
seen in osteoarthritis and rheumatoid arthritis. Primary cleavage of type II
collagen at the collagenase site is rate-limiting and is, therefore, a critical
step for its degradation. The major contributor to this cleavage was identified
in three isozymes of collagenase in human cartilage. Primary cultured human
chondrocytes were used for the study. The production of collagenase-1 was major
in total production for three isozymes of collagenase after stimulations with any
concentration of tumor necrosis factor-alpha and/or interleukin-1 at 48 and 72 h,
comprising 98% or greater of the total collagenase. When the production of
collagenase-1 was specifically suppressed by the transfection with duplexes of 21
nucleotide small interfering ribonucleic acid into the cells, the activity of
type II collagen cleavage was linearly decreased at neutral pH after activation.
The relative contribution of collagenase-1 to the primary cleavage of type II
collagen was determined to be 85%-93%. These findings suggest that collagenase-1
is a major contributor to the primary cleavage of type II collagens in human
cartilage and is a potential therapeutic target for osteoarthritis and rheumatoid
arthritis.
PMID- 17029061
TI - Clinical characteristics of Pneumocystis carinii pneumonia in patients with
connective tissue diseases.
AB - The characteristics of Pneumocystis carinii pneumonia (PCP) in patients with
connective tissue diseases (CTDs) were examined retrospectively. Nine patients
were enrolled in this study. Their mean age was 57.1 years. All the patients
received a high-dose steroid or immunosuppressant. The onset (mean 6.6 days) of
fever, cough, breathlessness, and geographical ground-glass opacities revealed by
chest computed tomography was acute. The serum beta-D: -glucan level increased
with a simultaneous increase in the Krebs von den Lungen (KL)-6 or surfactant
protein D level. The serum immunoglobulin G (IgG) and albumin levels and the
peripheral blood lymphocyte count at the onset of PCP were low, but only the
serum IgG level decreased significantly. The patients were treated with
trimethoprim-sulfamethoxazole or pentamidine isetionate. Six patients died
eventually: two patients of progressive respiratory failure, two probably due to
a recurrence of the PCP, and two with microbial respiratory infections other than
PCP. Five of the six patients required mechanical ventilation. Three patients
received secondary prophylaxis and survived. In conclusion, the acute onset was
characteristic of PCP in patients with CTDs. High-dose steroids,
immunosuppressants, and hypogammaglobulinemia are risk factors; and respiratory
failure requiring mechanical ventilation, severe secondary infections, and a lack
of secondary prophylaxis are poor prognostic factors. Secondary prophylaxis is
recommended for all of these patients.
PMID- 17029062
TI - Progressive facial hemiatrophy complicated by sclerodactyly, Raynaud's
phenomenon, anti-ribonucleoprotein antibody, and trigeminal nerve disturbance.
AB - A Japanese woman was diagnosed as having progressive facial hemiatrophy when she
was 26 years old. After 30 years, Raynaud's phenomenon and sclerodactyly suddenly
appeared; at the same time, positive rheumatoid factor and anti-ribonucleoprotein
(anti-RNP) antibody were noted on serological examinations. When she was 60 years
old, trigeminal nerve disturbance also appeared. The associations between
progressive facial hemiatrophy, systemic scleroderma, and trigeminal nerve
disturbance are interesting and should be discussed.
PMID- 17029063
TI - Anaphylactic reaction to infliximab in two rheumatoid arthritis patients who had
previously received infliximab and resumed.
AB - Here we report on two cases of anaphylactic reaction following infliximab
infusion in patients with active rheumatoid arthritis (RA). Both individuals had
received infliximab treatment during a clinical trial approximately 2 years prior
to further therapy; subsequent infusion of this agent led to anaphylactic
reactions in both cases. In light of these findings, we recommend that future
treatments with infliximab in RA patients who have previously received this agent
should be carefully monitored.
PMID- 17029064
TI - A case of Vogt-Koyanagi-Harada disease that developed relapsing polychondritis.
AB - We report the case of a 56-year-old Japanese man with Vogt-Koyanagi-Harada
disease in whom pain and diffuse swelling of the left auricle and bilateral
episcleritis developed 3 years after diagnosis. Biopsy of the left ear showed
acute chondritis, leading to another diagnosis of relapsing polychondritis.
Additionally, he was found to carry human leukocyte antigen DR4, which has been
reported to be associated with these inflammatory conditions. To our knowledge,
our patient is the first reported case of the occurrence of relapsing
polychondritis and Vogt-Koyanagi-Harada disease.
PMID- 17029065
TI - A patient with symptomatic osteomalacia associated with Fanconi syndrome.
AB - We report a patient with renal tubulointerstitial fibrosis and symptomatic
osteomalacia associated with Fanconi syndrome. A 55-year-old woman was
hospitalized because of an inability to walk. Beginning approximately 2 years
previously, she had experienced gradually worsening pain in the hips, shoulders,
and trunk, culminating in a bedridden state. Serum urea nitrogen was 38 mg/dl;
creatinine, 2.6 mg/dl; uric acid. 3.6 mg/dl; phosphate, 2.3 mg/dl; and alkaline
phosphatase, 2111 IU/l. Urinary beta2 microglobulin was 72 331 microg/day.
Aminoaciduria, renal glucosuria, and proximal renal tubular acidosis with a
normal anion gap were also noted. The patient was diagnosed with Fanconi
syndrome. Radiography demonstrated typical Looser zones in the proximal portion
of the left and especially the right femoral shaft, and at several other sites. A
renal biopsy specimen disclosed severe tubulointerstitial fibrosis with little
cellular infiltration. Glomeruli were largely intact. A bone biopsy specimen
indicated osteomalacia; no tetracycline labeling could be seen along most
trabecular bone surfaces, and the ratio of total osteoid volume to bone volume
was increased (71.8%). Bicarbonate administration (9 g/day) gradually lessened
most symptoms, permitting ambulation. Calcitriol administration decreased
excessive intact-parathyroid hormone emerging after 2 months of acidosis
correction. Thus, severe acidosis associated with Fanconi syndrome can induce
osteomalacia showing serious skeletal complications, but also responsiveness to
bicarbonate therapy.
PMID- 17029066
TI - Two cases of cervical abscess in rheumatoid arthritis patients.
AB - The prognosis of rheumatoid arthritis (RA) has recently been improved, resulting
in longer survival of patients. The incidence of oral diseases increases with
age, particularly for periodontal disease and those involving tooth decay, even
in normal healthy individuals. Patients with RA display increased incidence of
oral diseases, and the use of steroids or methotrexate to treat RA increases
susceptibility to infections, sometimes causing serious infections. We present
here two cases of cervical abscesses in RA patients who underwent emergency
surgery to treat oral infections due to the possibility of mediastinal
inflammation.
PMID- 17029067
TI - Levofloxacin-induced Achilles tendon rupture in a patient with systemic
microscopic polyangiitis.
AB - We report a case of spontaneous Achilles tendon rupture associated with
myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA)-related
microscopic polyangiitis in a 77-year-old man who was treated with oral
corticosteroids. Several days after 10 days of treatment with levoflaxacin (daily
dose 200 mg) for bacterial pneumonia, he noted discomfort around both Achilles
tendons. The discomfort developed into swelling around his left ankle, and he
could not walk well. We diagnosed bilateral Achilles tendinitis with spontaneous
rupture induced by levofloxacin. Epidemiological studies show that the risk of
fluoroquinolone-related tendon rupture is highest among patients over the age of
60 years who are receiving a corticosteroid. Rupture of the Achilles tendon is a
rare but serious side effect of fluoroquinolone usage. Thus, physicians should be
aware of this adverse effect, especially when prescribing medication for aged
patients being treated with corticosteroids.
PMID- 17029068
TI - A case of systemic lupus erythematosus: continued association of circulating
prolactin levels with disease activity over a 4-year follow-up period.
AB - Circulating prolactin levels in a woman with systemic lupus erythematosus (SLE)
were measured over a period of 4 years, and her hyperprolactinemia remained
associated with disease activity throughout. Circulating prolactin could thus be
a better practical marker than standard parameters such as anti-double-stranded
DNA antibodies and serum complement in some patients with SLE.
PMID- 17029069
TI - A lupus-like butterfly rash following infliximab therapy.
PMID- 17029070
TI - Osteoimmunological insight into bone damage in rheumatoid arthritis.
AB - Research into the bone destruction associated with rheumatoid arthritis has
highlighted the importance of the interplay of the immune and skeletal systems.
Arthritic bone destruction is attributable to the defective control of
osteoclastogenesis by T cells. We revealed that excessive expression of receptor
activator of NF-kappaB ligand (RANKL) and a paucity of interferon-gamma underlie
the enhanced osteoclastogenesis in arthritis. The interdisciplinary research
field called osteoimmunology has attracted further attention after identification
of a number of unexpected bone phenotypes in mice lacking immunomodulatory
molecules. Accumulating evidence suggests that the immune and skeletal systems
share not only cytokines but also various signaling molecules, transcription
factors, and membrane receptors. Thus, bone turns out to be a dynamic tissue that
is constantly renewed, where the immune system participates to a hitherto
unexpected extent. This emerging field will be of great importance for a better
understanding and treatment of rheumatic diseases.
PMID- 17029071
TI - Mechanisms of bone loss in rheumatoid arthritis.
AB - Rheumatoid arthritis (RA) is an autoimmune inflammatory disease in which
destruction of bone in the joints causes major morbidity. Recent research has
shed light on the cell and molecular mechanisms that lead to this osteolysis, all
due directly or indirectly to the chronic inflammation. The aspects of this
research covered in this review include the alteration of cell proliferation and
survival that results in growth of the RA synovium. This process depends upon an
increase in angiogenesis and local blood flow, which is also a feature of
increased bone turnover. In addition, the inflammatory environment increases
expression of chemokines, which are involved in the recruitment of monocytic
osteoclast precursors. Chronic inflammation also promotes an overall catabolic
state, with increased osteoclast differentiation and resorptive activity, driven
by disregulation of receptor activator of NF-kappaB ligand (RANKL) and the
synergistic activity of inflammatory cytokines such as tumor necrosis factor
alpha and interleukin-1. Osteoclast survival is increased in this environment,
but osteoblast differentiation and survival are decreased, with a consequent
reduction in bone formation and a net loss of bone. Recognition of these
processes and the factors involved will enable more effective and targeted
treatments for RA.
PMID- 17029072
TI - Long-term outcome of patients with rheumatoid arthritis treated by multiple
arthroplasty.
AB - We conducted a study of 82 patients with rheumatoid arthritis (RA) who had
undergone multiple arthroplasty and investigated their clinical findings and
clinical courses. We reviewed the significance of multiple arthroplasty in the
treatment of RA, its problems, and measures to solve them. All patients initially
regained and maintained good walking capacity. However, the walking capacity of
many patients again decreased over the long term; in the tenth year, 79% of
patients were capable of a practical gait. The causes of decreased walking
capacity included complications of artificial joints, cervical lesions, and
vertebral compression fractures. Fractures were observed in as many as nine
patients, indicating that it is important to prevent and treat their cause, that
is, osteoporosis. The survival rate was 71% in 10 years. In RA patients,
particularly those who have undergone multiple arthroplasty, the major causes of
death are infection and rheumatic disease, suggesting that prevention of such
diseases should be considered paramount. Appropriate systemic treatment of RA,
patient education, and measures against osteoporosis for prevention of
complications may preserve the worth of multiple arthroplasty for RA patients
with multiple joint destruction.
PMID- 17029073
TI - Effect of G-1 column (Adacolumn) therapy in rats with adjuvant arthritis on the
migration and immunoreactivity of peripheral and splenic leukocytes.
AB - The G-1 column (Adacolumn), a novel extracorporeal adsorption device, is now
available for the treatment of such chronic inflammatory diseases as ulcerative
colitis and rheumatoid arthritis. G-1 column treatment sometimes results in a
rapid decrease in clinical inflammatory parameters and/or has a delayed
beneficial effect on disease activity. In order to identify the scientific basis
for such clinical benefits, we studied rats with adjuvant arthritis induced by
immunization with Mycobacterium butyricum antigen. The potential role of G-1
column treatment on the migratory properties and immunoreactivities of leukocytes
was investigated. Treatment of arthritic rats for 60 min with an extracorporeal
perfusion through the G-1 column led to the adsorption of a small proportion
(20%) of circulating granulocytes and monocytes. However, after G-1 treatment,
the migration of radiolabeled blood granulocytes and monocytes to sites of acute
dermal inflammatory reactions decreased significantly, in the case of
granulocytes, almost by half. The migration of granulocytes to the inflamed
hindpaws of severely affected animals was diminished in the G-1 treated group.
Granulocytes that have passed through the G-1 column may stay in the bloodstream
because of their markedly diminished number of adhesion molecules. A slightly
increased accumulation in the liver and a decreased localization in the lung was
also observed. These results may be relevant to the rapid clinical anti
inflammatory effect observed in rheumatoid arthritis and possibly also in
ulcerative colitis, without any pulmonary complications. In contrast, the
adsorption rate by the G-1 column of T lymphocytes was very low, and their
migration pattern to sites of dermal inflammatory reactions was not altered after
treatment. However, the antigen (Mycobacterium purified protein derivative)
reactivity of T lymphocytes in blood was almost completely abolished after G-1
column treatment of arthritic rats. This unexpected qualitative effect on T
lymphocytes of G-1 treatment warrants further detailed study.
PMID- 17029074
TI - Clinical characteristics of anti-glucose-6-phosphate isomerase antibody-positive
Japanese patients with rheumatoid arthritis.
AB - Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are known to be
arthritogenic in mice. These Abs are elevated in several forms of arthritic
condition in humans, although their prevalence in rheumatoid arthritis (RA)
patients is still in debate. Some RA patients have increased levels of anti-GPI
Abs, but their clinical manifestation and relevance to other Abs are not clearly
elucidated. The aims of this study were to explore the clinical and hematological
characteristics of RA with anti-GPI Abs, and to compare their prevalence in RA
patients, systemic lupus erythematosus (SLE) patients, and healthy subjects (HS)
in a Japanese population. Anti-GPI Abs were positive in 16 patients with RA (12%,
n = 137), in 10 patients with SLE (8%, n = 131), and in 6 HS (4%, n = 139). C
reactive protein (CRP), immunoglobulin G, and the antinuclear antibody titer were
higher in anti-GPI-positive patients than in those who were negative (P = 0.049,
P = 0.0003, and P = 0.002, respectively). Moreover, the positivity of anti-GPI
Abs was correlated with CRP more than with rheumatoid factor in RA patients. It
is unclear whether anti-GPI Abs can predict the progress of disease, but the
prevalence of these Abs was higher in active RA patients with severe arthritis,
suggesting that anti-GPI Abs may be related to the pathogenesis of severe forms
of arthritis.
PMID- 17029075
TI - Inhibitory effect of mizoribine on matrix metalloproteinase-1 production in
synovial fibroblasts and THP-1 macrophages.
AB - To investigate the mechanism of antirheumatic action of mizoribine (MZR), we
examined the expression of matrix metalloproteinase-1 (MMP-1) and MMP-3 utilizing
THP-1 derived macrophage-like cells (THP-1 macrophages) and human synovial
fibroblasts (SFs). The cells were respectively stimulated with lipopolysaccharide
(LPS) and interleukin-1beta in the presence or absence of MZR in vitro. The
concentrations of MMP-1 and MMP-3 in the supernatant were measured by enzyme
linked immunosorbent assay. The secretion of MMP-1 from SFs, as well as THP-1
macrophages, was inhibited by MZR in a dose-dependent manner. Furthermore, a
quantitative real-time polymerase chain reaction revealed that MZR decreased the
expression of MMP-1 messenger RNA. These findings may be an explanation for the
clinical effect of MZR in patients with rheumatoid arthritis.
PMID- 17029076
TI - Follow-up study of ankle arthrodesis in severe hind foot deformity in patients
with rheumatoid arthritis using an intramedullary nail with fins.
AB - We report herein a retrospective study of 25 cases of ankle arthrodesis performed
in 23 patients with rheumatoid arthritis (RA) using an intramedullary nail with
fins, developed in 1994. Surgical treatment, postoperative management, and
clinical evaluation are described. Clinical evaluation, at an average follow-up
period of 7 years 1 month, was based on foot disease scores from the Japanese
Orthopedic Association; we compared these scores pre- and postoperatively, and
during follow-up. These parameters showed a significant difference between
preoperation and the follow-up period. However, instability only significantly
improved when compared between pre- and postoperation. Arthrodesis using an
intramedullary nail with fins was effective for the treatment of severe deformity
of the hind foot. Nonunion was not observed and no remarkable changes of the
Chopart joint were recognized between preoperation and the follow-up period. In
our series, delayed wound healing was recognized in 6 of 25 joints. However,
infection or neuropathy and other complications were not found. Arthrodesis using
an intramedullary nail with fins is a viable treatment option for severe
deformity of the hind foot in RA patients, because nonunion was not recognized
and the clinical results over an average 7-year follow-up period were good or
satisfactory.
PMID- 17029077
TI - The relationship between initial clinical manifestation and long-term prognosis
of patients with systemic lupus erythematosus.
AB - The relationship between clinical manifestations and prognosis was examined and
evaluated among systemic lupus erythematosus (SLE) patients. A total of 542
patients with SLE were selected and divided into nine groups according to their
main clinical manifestation at the time of initial diagnosis. The relationship
between these clinical manifestations and long-term prognosis was evaluated in
respect to the survival, remission, relapse rates, the development of a new
clinical manifestation, and/or damage index. Patients with neuropsychiatric SLE
(NPSLE), accompanied with acute confusional state/seizure disorder, cerebral
vascular disease, or pneumonitis had poor survival rates with cause of death
related to their major organ involvement. Patients with nephropathy or leukopenia
had lower remission rates, and an increase in relapse rates was frequently
recognized in patients with pneumonitis. Body damage (damage index) was higher in
patients with lupus psychosis, pneumonitis, and/or arthritis. The translation of
the main manifestations after diagnosis was confirmed in 64 patients (11.8%), and
often observed in patients with autoimmune hemolytic anemia and arthritis. The
majority of these manifestations were nephropathy, NPSLE, thrombocytopenia, and
pneumonitis, and the prognosis of patients with nephropathy and thrombocytopenia
as a new main manifestation had a poor outcome. The results of long-term
prognosis in SLE greatly differed with respect to the initial clinical
manifestation at the time of diagnosis.
PMID- 17029078
TI - Reactive arthritis after influenza vaccination: report of a case.
AB - We describe a patient with reactive arthritis (ReA) induced by influenza
vaccination. A healthy 79-year-old Japanese man began suffering from migrating
polyarthritis 2 days after receiving influenza vaccine. He proved negative for
rheumatoid factor, showing no evidence for microbial infections such as
Streptoccocci, Chlamydia, or Parbovirus B19. Human leukocyte antigen (HLA) typing
analysis revealed positive results for HLA-B54 (22), which is one of the cross
reactive antigens to HLA-B27. His arthritis improved with administration of
nonsteroidal anti-inflammatory drugs, and recovery was attained within 6 weeks.
Reactive arthritis is a rare adverse effect induced by influenza vaccination;
however, it is important that it is recognized by all physicians.
PMID- 17029079
TI - Intra-articular osteoid osteoma protruding from the acetabular fossa.
AB - Osteoid osteoma is rarely found in the acetabular fossa. We treated a case of
osteoid osteoma that had developed into a mass lesion and protruded from the
acetabular fossa with synovitis. In this case, a well-defined bony tumor located
in the acetabular fossa was detected by plain radiographs and computed tomography
scans. Gadolinium-enhanced T1-weighted magnetic resonance (MR) images obtained
with fat saturation indicated distinctive features in which the central area of
the lesion and hyperemic synovium were enhanced. A surgical specimen contained
the nidus, and osteoid osteoma was diagnosed. Retrospectively, this MR sequence
demonstrated the characteristic nidus and synovitis, and it may thus be valuable
in cases where diagnosis of intra-articular osteoid osteoma is difficult.
PMID- 17029080
TI - Characteristic appearance of large subcutaneous gouty tophi in magnetic resonance
imaging.
AB - The development of multiple large tophi in patients with gout is rare. We report
magnetic resonance (MR) and histological features of large subcutaneous tophi in
a 32-year-old male patient with no known arthritis. His subcutaneous lesions were
confused with a neoplastic process, evaluated by MR imaging, and surgically
excised after biopsy. The honeycomb-like appearance on the gadolinium-enhanced
images may reflect the characteristic multilobular structure of the tophi
composed of avascular urate deposits and surrounding vascularized granulation
tissue.
PMID- 17029081
TI - The onset of Graves' disease during the clinical course of myeloperoxidase
antineutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis.
AB - A 47-year old man presented with atrial fibrillation, weight loss, hand tremor,
and hyperperspiration concurrent with the reactivation of the disease activity of
myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated
glomerulonephritis. Laboratory findings indicated that the hyperthyroidism had
already existed when glomerulonephritis was detected, and Graves' disease became
evident while decreasing the dose of prednisolone. Although the levels of thyroid
stimulating hormone receptor antibody, antithyroid peroxidase antibody, and
myeloperoxidase antibody increased, both disease activities were suppressed by
increasing the dose of prednisolone. This case indicates that MPO-ANCA-associated
glomerulonephritis and Graves' disease may share a common pathogenesis.
PMID- 17029082
TI - Total knee arthroplasty with a long-stemmed component for fractures adjacent to
the knee in rheumatoid arthritis: a report of four cases.
AB - Four rheumatoid arthritis patients with fractures adjacent to the knee were
treated by total knee arthroplasty with a long-stemmed component. All four
fractures healed; joint reconstruction and limb realignment were achieved
simultaneously. Total knee arthroplasty with a long-stemmed component was useful
in stabilizing the fracture and rapidly restoring function in the joint and the
limb.
PMID- 17029083
TI - No change of infliximab levels in stored blood for preoperative autologous blood
donation: a preliminary report.
PMID- 17029084
TI - Doppler sonographic evaluation of infliximab therapy for rheumatoid arthritis.
PMID- 17029085
TI - Plantar heel pain and its 3-mode 4-stage treatment.
AB - The most common cause for heel pain is plantar fasciitis. The diagnosis can
usually be made by clinical examination, but sometimes ENMG
(electroneuromyography), ultrasound, and magnetic resonance imaging examinations
are helpful. Other reasons for heel pain, e.g., nerve entrapments,
atherosclerosis/ischemia, and fat pad degeneration, should be excluded. Plantar
fasciitis can also present a symptom of chronic seronegative
spondyloarthropathies or reactive arthritis. In the case of common plantar
fasciitis, three different modes of treatment can be administered, namely, (1)
anti-inflammatory and analgesic treatment, (2) rest and diminution of the strain
at the insertion, and (3) maintenance of the tension and flexibility of the soft
tissues. A simple four-step treatment plan algorithm, based on symptoms, their
duration, and response to treatment, is presented. Operative treatment is seldom
needed if the algorithm is correctly followed. Operative treatment is recommended
only when the pain remains resistant to conservative treatment after more than 1
year. For operative treatment, partial release of the fascia close to insertion
to avoid flat foot and secondary strain on the calcaneocuboid and midtarsal
(Lisfranc) joints is our preferred option.
PMID- 17029086
TI - Granzyme B and natural killer (NK) cell death.
AB - Granzyme B is a unique serine protease, which plays a crucial role for target
cell death. Several mechanisms of delivery of granzyme B to target cells have
been recently identified. Granzyme B directly activates Bid, a specific substrate
for granzyme B, resulting in caspase activation. Granzyme B efficiently cleaves
many prominent autoantigens, and the hypothesis that autoantibodies arise when
cryptic determinants are revealed to the immune system has been proposed. Some
autoantibodies directed against granzyme B-specific neoepitopes are present in
serum from patients with autoimmune diseases. In the tissues from autoimmune
diseases, granzyme B might play an important role for disease progression (i.e.,
rheumatoid arthritis synovium) or inhibition (i.e., regulatory T cells). We have
identified a novel type of activation-induced cell death (granzyme B leakage
induced cell death). Activation-induced natural killer (NK) cell death is
accompanied by the leakage of granzyme B from intracellular granules into the
cytoplasm, and it triggers apoptosis by directing Bid to mitochondrial membranes.
An excess of "leaked" granzyme B over its inhibitor, serpin proteinase inhibitor
9, is a major determinant of cell death. The role of granzyme B in autoimmunity
and its influence on NK cell death are discussed.
PMID- 17029087
TI - Therapeutic effects of the combination of methotrexate and bucillamine in early
rheumatoid arthritis: a multicenter, double-blind, randomized controlled study.
AB - Disease-modifying antirheumatic drug (DMARD) combination therapies are used
widely, but there have been few reports clearly demonstrating that combination
therapy is more effective than DMARD monotherapy. We conducted a multicenter,
double-blind controlled trial in order to clarify that the combination of
methotrexate and bucillamine is more effective than either alone. The subjects of
this study were 71 patients with active rheumatoid arthritis within 2 years of
onset. Dosages were 8 mg methotrexate with 5 mg folic acid per week (MTX group),
200 mg bucillamine per day (BUC group), or both MTX and BUC (combination group).
Clinical effects and adverse reactions were observed for 96 weeks. The ACR 20
response rate was 79.2% in the combination group, significantly higher than the
rates of 43.5% for the MTX group (P = 0.008) and 45.8% for the BUC group (P =
0.0178). The cumulative survival curve of maintaining the ACR 20 response was
significantly higher in the combination group than in the MTX and BUC groups (P =
0.0123 and P = 0.0088, respectively). The mean increase in the total Sharp score
over 96 weeks was 12.6 +/- 9.0 in the combination group, significantly lower (P =
0.0468) than the value of 28.0 +/- 28.3 for the single DMARD (combined MTX and
BUC) group. The incidence of adverse reactions did not differ significantly
between the three groups. It was concluded that the combination therapy with MTX
and BUC showed significantly higher clinical efficacy than either of the single
DMARD therapies.
PMID- 17029088
TI - A study of ten Japanese patients with seronegative spondylarthropathy: a
tentative proposal.
AB - We reviewed ten patients with seronegative spondylarthropathy (SNSA), who all
fulfilled the European Spondylarthropathy Study Group criteria for
spondylarthropathy (SpA); seven patients also met the Amor criteria for SpA.
Seronegative spondylarthropathy was not a uniform syndrome but rather a wide
spectrum of complex disease with characteristics of sacroiliitis and
enthesopathy. The most frequent symptom at diagnosis of SNSA was inflammatory low
back pain, followed by asymmetric oligoarthralgia and Achilles tendonitis and/or
plantar fasciitis. Systemic complications were revealed as eye and skin
involvement. Imaging methods including pelvic radiography, scintigraphy, and
computed tomography scanning were useful in detecting spondylarthropathic
changes, which were characteristic of SNSA. Human leukocyte antigen (HLA) typing
showed various patterns among patients, in which HLA-B27 was positive in three
patients with ankylosing spondylitis. HLA-B51, which is a well-known genetic
factor associated with Behcet's disease (BD), was positive in two patients who
were apparently distinct from BD. Two patients with palmoplantar pustulosis
showed symptoms and signs characteristic of SNSA. Although we have few SNSA
patients in the present study, we would like to propose that HLA-B51 positive SpA
would be considered as a subset of SNSA, and that pustulotic SpA also would be
classified as a member of SNSA. This led us to suggest the possibility to change
the concept of SNSA proposed by Moll et al. The optimal treatment remains to be
defined, but sulfasalazine was effectively used with almost all patients in
combination with nonsteroidal anti-inflammatory drugs.
PMID- 17029089
TI - Comparison in values of color flow signals and vascular resistance of synovial
vascularity demonstrated by Doppler sonography between knee and
metacarpophalangeal joints of patients with rheumatoid arthritis.
AB - Synovial vascularity of 12 patients with rheumatoid arthritis (RA) was examined
by Doppler sonography for color flow signals and vascular resistance on knee
joints and metacarpophalangeal (MCP) joints, and the results were compared with
each other and with C-reactive protein (CRP) levels of the patients. A
significant correlation was observed between knee resistance index (RI) and MCP
RI (P = 0.0140), but not between knee color flow signals and MCP color flow
signals (P = 0.1029). A significant correlation was also observed between knee
color flow signals and knee RI (P = 0.0107), and knee pulsatility index (PI) (P =
0.0146). On the other hand, no correlation was observed between MCP color flow
signals and MCP-RI (P = 0.828), and MCP-PI (P = 0.434). There was no significant
correlation between CRP levels and grades of color flow signals, RI, and PI for
both knee and MCP joints. Doppler sonographic evaluation of RI, especially knee
RI, could be a useful marker for estimating synovial inflammation in RA patients.
PMID- 17029090
TI - Prevalence of Helicobacter pylori infection and risk of upper gastrointestinal
ulcer in patients with rheumatoid arthritis in Japan.
AB - We evaluated the prevalence of Helicobacter pylori infection and the association
of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use
with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with
rheumatoid arthritis (RA). Using the clinical database of the cohort of RA
patients and the serum titers of H. pylori antibody, 1815 patients were analyzed.
Clinical data were successfully collected for 1529 patients over 2 years, and the
history of NSAID use and the occurrence of newly diagnosed UGI ulcer were
ascertained by patient self-reports and confirmed by their medical records. A
total of 871 patients (49.3%) were H. pylori antibody-positive. Rates of
positivity for H. pylori in patients with and without NSAID use were 47.5% and
54.7%, respectively (odds ratio = 0.75, 95% confidence intervals [CI]: 0.58
0.96). The incidence of newly diagnosed UGI ulcer was 0% in the H. pylori-/NSAID-
group, 1.24% in the H. pylori-/NSAID+ group, 1.06% in the H. pylori+/NSAID-
group, and 3.46% in the H. pylori+/NSAID+ group. The odds ratios of H. pylori
infection and NSAID for the occurrence of new UGI ulcers after adjusting for age
and sex were 2.97 (95% CI: 1.19-7.38) and 4.31 (95% CI: 0.57-32.4), respectively.
Although the prevalence of H. pylori antibody was low in patients with RA
compared with that in healthy Japanese individuals, H. pylori infection was a
significant risk factor for UGI ulcer in patients with RA.
PMID- 17029091
TI - Macrophages that have phagocytosed particles are capable of differentiating into
functional osteoclasts.
AB - The aim of the current study was to determine whether human macrophages that have
phagocytosed particles are capable of differentiating into osteoclastic bone
resorbing cells. Macrophages isolated from human peripheral blood were cultured
with latex particles in the presence of receptor activator of nuclear factor (NF)
kappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) on dentine
slices and coverslips. After 24 h incubation, particles that had not yet been
phagocytosed were removed by washing the slices. Histochemistry and
immunohistochemistry was used to determine expression of macrophage and
osteoclast markers and lacunae resorption, scanning electron microscopy, and
transmission electron microscopy were used to examine cells with phagocytosed
particles. Isolated macrophages on dentine slices were noted to contain a large
number of particles inside, and no particles were identified outside of culture
cells after washing. After 14 days of incubation, numerous tartrate-resistant
acid phosphatase-positive multinucleated cells that contained particles in their
cytoplasm, capable of extensive lacunae bone resorption, formed in these
cultures. Our results clearly indicated that macrophages that have phagocytosed
particles were still capable of differentiating into osteoclastic bone-resorbing
cells. Macrophages that have phagocytosed wear particles in the pseudomembrane
surrounding an implant not only produce cytokines but also may differentiate into
functional osteoclasts, and influence bone resorption and loosening of a
prosthesis.
PMID- 17029092
TI - Bone resorption of the facet joint in rheumatoid arthritis as a predictor of
lower cervical myelopathy.
AB - The purpose of the present study was to identify the risk factors to predict
instability of the subaxial cervical spine and cervical myelopathy based on plain
radiographs. The study was performed on 99 patients with mutilating rheumatoid
arthritis (RA). From plain lateral radiographs of the cervical spine over time,
rheumatoid cervical spine lesions were investigated and evaluation was made on
the possibility to develop cervical myelopathy. The incidence of subaxial
cervical spine lesions in the patients with mutilating RA was as high as 98%. In
particular, resorption of the superior facet suggests high risk to develop
cervical myelopathy. The presence of spinous process erosion is also likely to
reveal such a possibility. There was no statistically significant difference in
the anteroposterior diameter of cervical spinal canal between the cases with
cervical myelopathy and those without it. Resorption of the superior facet is the
most important factor for the development of cervical myelopathy. In the cases
with rheumatoid cervical spine lesions, it is necessary to take special notice of
the superior facet.
PMID- 17029093
TI - An unusual complication of familial Mediterranean fever: protracted arthritis
with bilateral coxarthrosis and intraosseous amyloidosis of femoral head.
AB - Protracted arthritis is uncommon in familial Mediterranean fever (FMF) and rarely
may result in degenerative joint damage, a well-known complication of FMF,
usually affecting kidneys. We present an unusual case of FMF involving severe
bilateral coxarthrosis leading to residual incapacity that was treated by total
hip arthroplasty, and an unusual presentation of amyloidosis - intraosseous
amyloidosis of the femoral head.
PMID- 17029094
TI - Massive mesenteric edema in a patient with type I hereditary angioedema.
AB - We report a patient with hereditary angioedema (HAE) presenting with skin edema
and abdominal pain. Laboratory examination showed reduced levels of CH50, C2, C4,
and C1 inhibitor (C1-INH). Abdominal computed tomography (CT) showed marked
mesenteric edema and wall thickening of the duodenum and transverse colon. Acute
abdominal pain is common in HAE and is difficult to distinguish from surgical
emergency. Massive mesenteric edema on CT is a rare, but specific, sign
suggesting HAE.
PMID- 17029095
TI - Utility of grommets for implant arthroplasty of the great toe in a patient with
rheumatoid arthritis: a case report.
AB - We report a case of rheumatoid arthritis treated by bilateral flexible hinge toe
implant arthroplasty, using grommets only on one side, which resulted in
bilateral fractures requiring removal of the implants 6.5 years after the
surgery. Both implants were completely fractured at the bottom of the distal
stems. Macroscopically, synovitis was present around both fractured stems,
although the severity of synovitis and fragmentation of the fractured implant was
relatively mild on the right side in which grommets were used. The shape of the
body of the fractured implant was relatively preserved on the right side in which
grommets were used. There was no damage or fracture of the grommets. The grommet
might have acted to prevent pressures and scratches that would cause synovitis
and deformity of the body of the implant, but might not completely prevent
fractures of implants.
PMID- 17029096
TI - A case of systemic lupus erythematosus presenting transverse myelitis after an
episode of meningitis.
AB - A 27-year-old woman suffering from systemic lupus erythematosus was admitted
because she had motor and sensory palsy of the lower extremities, neck stiffness,
and a fever. Cerebrospinal fluid study indicated meningitis, and magnetic
resonance imaging revealed cord swelling and high signals at Th9-Th12 levels.
Antibiotics treatment led to resolution of the meningeal signs. Intravenous
cyclophosphamide and prednisolone resulted in a partial recovery from the
transverse myelitis neurological disturbance.
PMID- 17029097
TI - A case of systemic sclerosis sine scleroderma associated with perforation of an
afferent loop after subtotal gastrectomy with Billroth 2 anastomosis for its
severe gastrointestinal involvement.
AB - A 50-year-old man was admitted to hospital for dysphagia. The upper
gastrointestinal series revealed esophageal stricture, pyloric stenosis, and
hypomotile small intestine. He was diagnosed with systemic sclerosis sine
scleroderma with gastrointestinal involvement. After subtotal gastrectomy with
Billroth 2 anastomosis, he had recurrent intestinal pseudo-obstruction and
perforation of the afferent loop. Our experience indicates that surgical
procedures in bowel scleroderma, in which an afferent loop is reconstructed,
could easily cause perforation of the afferent loop.
PMID- 17029098
TI - Human urinary trypsin inhibitor bolus infusion improved severe interstitial
pneumonia in mixed connective tissue disease.
AB - Interstitial pneumonia (IP) with mixed connective tissue disease (MCTD) often
progresses despite immunosuppressive therapies that caused serious infections.
Human urinary trypsin inhibitor (UT) inhibits inflammatory factors associated
with IP, without immunosuppression. UT bolus infusion rescued a female MCTD
patient with refractory IP and severe opportunistic fungal pneumonia. Her IP
diminished with monthly UT bolus infusion despite tapering of prednisolone,
without UT-related side effects. UT pulse therapy could prove beneficial for
refractory IP in MTCD even with opportunistic infections.
PMID- 17029099
TI - Asymptomatic interstitial pneumonitis induced by bucillamine in a patient with
rheumatoid arthritis.
PMID- 17029100
TI - Removal of dying cells and systemic lupus erythematosus.
AB - Systemic lupus erythematosus (SLE) is a very heterogeneous systemic autoimmune
disease, in which autoantibody synthesis against nuclear constituents is the main
immunological characteristic. These autoantibodies underwent affinity maturation
and isotype switching. Additionally, T-cell tolerance against nuclear
autoantigens should be affected in these autoimmune patients. Nuclear material
derived from apoptotic and/or necrotic cells may serve as an important source of
autoantigens. However, dead and dying cells as well as cellular debris are
rapidly removed from tissues by phagocytes without eliciting inflammation or
immune responses under healthy conditions. During apoptosis nuclear components
are strongly modified through enzymatic reactions. If these cells are not timely
cleared, those autoantigens may be released, taken up, and presented by dendritic
cells in tissues or presented by follicular dendritic cells in lymph nodes to T
and B cells, respectively. This could be a mechanism for breaking the peripheral
self-tolerance. In this article we focus on the deficient clearance of apoptotic
cells in SLE patients and its importance in development of this autoimmune
disease.
PMID- 17029101
TI - Involvement of cyclic guanosine monophosphate-dependent protein kinase II in
chondrocyte hypertrophy during endochondral ossification.
AB - During vertebrate skeletal development, the appendicular skeleton forms through
endochondral ossification, which involves the intricately regulated multistep
differentiation of mesenchymal cells. During this process, mesenchymal
condensations initially differentiate into chondrocytes. Then chondrocytes in the
center further differentiate into hypertrophic chondrocytes. Hypertrophic
chondrocytes express a number of osteogenic factors and induce bone formation.
Although numerous studies have provided novel insights into the regulation and
function of cartilage development, little is known about the intracellular
signaling pathways regulating chondrocyte hypertrophy. Recent study revealed that
cyclic guanosine monophosphate (cGMP)-dependent protein kinase II (cGKII) coupled
the stop of proliferation and the start of hypertrophic differentiation of
chondrocytes. Herein, we review the molecular mechanism of regulation of
chondrocyte hypertrophy by cGKII and the interaction between cGKII and other
signaling pathways.
PMID- 17029102
TI - Pharmacokinetics, efficacy, and safety of short-term (12 weeks) etanercept for
methotrexate-refractory polyarticular juvenile idiopathic arthritis in Japan.
AB - We examined and evaluated the pharmacokinetics, efficacy, and safety of
etanercept in patients with methotrexate (MTX)-refractory polyarticular juvenile
idiopathic arthritis (JIA) in Japan. All MTX-refractory polyarticular JIA
patients 4-17 years old received 0.4 mg of etanercept per kilogram of body weight
subcutaneously twice weekly for up to 3 months in the open-label, prospective,
and multicenter trial. A response was defined as an improvement of 30%, 50%, 70%,
or more from baseline in at least three of six indicators of disease activity,
with no more than one indicator worsening by more than 30% from baseline (30%,
50%, or 70% definition of improvement, respectively), and disease activity score
(DAS28) by EULAR (European League Against Rheumatism) response criteria. At the
end of the 12-week study, 20 of the 22 patients (90.9%) had responses with both
30% and 50% definition of improvement after etanercept treatment. To our
surprise, 15 of 22 patients (68.2%) had a response with 70% definition of
improvement. Moreover, in DAS28, eight patients were evaluated as having a good
response and there were no patients with a poor response to etanercept. Treatment
had to be stopped in one patient who developed joint contracture during the study
period, but there were no significant adverse events in the other patients. In
conclusion, treatment with etanercept leads to significant improvement in
patients with active polyarticular JIA in Japan. Etanercept is well tolerated by
pediatric patients as well as adults.
PMID- 17029103
TI - Serum levels and pharmacodynamics of methotrexate and its metabolite 7-hydroxy
methotrexate in Japanese patients with rheumatoid arthritis treated with 2-mg
capsule of methotrexate three times per week.
AB - Methotrexate (MTX) is the first-choice drug for rheumatoid arthritis (RA);
however, the pharmacodynamics of MTX in Japanese patients with RA treated
legitimately according to the government recommended dosage, 6 mg per week, are
unknown. Methotrexate and its metabolite, 7-hydroxy MTX (7-OH MTX), were measured
in sera of 16 outpatients with active RA in the first week of MTX treatment and 4
12 weeks after the introduction at 0, 1, 2, 4, and 8 h after administration of
the first and the third 2-mg capsule, followed by sampling at 48, 96, and 168 h.
The mean maximal serum drug concentration (mean C(max)) of MTX attained at 1-2 h
after ingestion of the first capsule was 0.215 and 0.252 microM, respectively, in
the first and the follow-up week. The mean C(max) after ingestion of the third
capsule was 0.223 microM and 0.357 microM. The mean C(max) of 7-OH MTX was 0.0334
and 0.0289 microM for the first capsule, and 0.0495 and 0.0672 microM for the
third capsule. The results indicate that MTX does not accumulate or deposit in
the body of Japanese patients with RA when treated with 6 mg per week, and
pharmacodynamics of MTX are comparable to those in overseas patients treated with
7.5 mg per week.
PMID- 17029104
TI - The study of bone mineral density and bone turnover markers in postmenopausal
women with active rheumatoid arthritis.
AB - The aim of this study was to investigate determinants of reduced bone mineral
density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and
to evaluate whether there are common markers of bone loss. We evaluated BMD of
the femoral neck using dual-energy X-ray absorptiometry, and the measured
biochemical markers included serum bone-specific alkaline phosphatase (BALP),
serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I
collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked
immunsorbent assay, and OC was measured using an immunoradiometric assay. One
hundred and forty postmenopausal Japanese women who had not received treatment
with bisphosphonates or hormone replacement therapy were entered into the study.
Thirty-four patients (41.0%) had femoral osteopenia (T score -1 to -2.5) and 23
patients (27.7%) had osteoporosis (T < -2.5). The body mass index of patients
with normal BMD (T score >or= -1.0) was significantly higher (P < 0.01) than in
patients with osteoporosis at the femoral neck. The T score exhibited a
significant negative correlation with age and the duration of RA disease. Serum
BALP and serum OC, markers of osteoblast function, were negatively related to
erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix
metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function,
exhibited a positive correlation with ESR, CRP, and MMP-3. From these results,
this study suggests that generalized bone loss occurs in active RA and is
characterized by evidence of bone resorption that is correlated with the high
levels of inflammation. Body mass index, disease duration, and high serum NTx
level were common risk factors in osteoporosis of postmenopausal women with RA.
PMID- 17029105
TI - Production of interleukin-6 and interleukin-8 by nurse-like cells from rheumatoid
arthritis patients after stimulation with monocytes.
AB - It has been reported that nurse-like cells (NLCs) play a critical role in the
pathogenesis of rheumatoid arthritis (RA). The interaction between NLCs
established from RA patients (RA-NLCs), and freshly isolated blood monocytes was
analyzed to further elucidate the pathogenesis of RA. RA-NLC lines were
established from the synovium of RA patients. The RA-NLCs were cultured with
monocytes freshly isolated from peripheral blood of healthy donors, and induction
of interleukin (IL)-6 and IL-8 as well as the mRNA expression of these cytokines
was examined. The levels of IL-6 were over 400 times higher in the supernatant
from coculture of RA-NLCs and monocytes than in those from cultures of RA-NLCs
alone. Anti-tumor necrosis factor (TNF)-alpha monoclonal antibody inhibited the
induction of both cytokine in a dose-dependent fashion, although there was no
detectable level of TNF-alpha in the supernatant from coculture. In addition,
coculture of RA-NLCs and monocytes without direct cell contact did not induce
cytokine production. To determine IL-6 producing cells, RA-NLCs and monocytes
were separated into each fraction after coculture for 24 h. Cocultured RA-NLCs
contained approximately 80 times higher IL-6 mRNA than the RA-NLCs cultured
alone. The levels of IL-8 were also much higher (about 900 times) in the
supernatant from coculture than in those from cultures of RA-NLCs alone.
Cocultured RA-NLCs expressed IL-8 mRNA about 620 times higher than those cultured
alone. These results indicate that NLCs produce high levels of IL-6 and IL-8
after cell-cell interaction with monocytes/macrophages via membrane-bound TNF
alpha, and that activation of NLCs by monocytes/macrophages may be involved in
the pathogenesis of RA through maintenance of synovial inflammation.
PMID- 17029106
TI - Identification of three novel peptides that inhibit CD40-CD154 interaction.
AB - The CD40-CD154 interaction is an attractive target for therapeutic intervention
in various autoimmune disorders, including rheumatoid arthritis, systemic lupus
erythematosus (SLE), multiple sclerosis, and myasthenia gravis. In this study, to
develop a new disruption strategy of the CD40-CD154 interaction, we screened for
peptides with inhibitory effects on such ligation. 2 x 10(11) phage display
libraries displaying liner peptides of 12-mer amino acids were screened by CD40
Ig binding assay and eight phages which expressed a different respective peptide
(40BP-1 to -8) were able to specifically bind to CD40. Competitive inhibition
analyses showed that 3 of the 8 peptides (40BP-N1-1 - APELPNMTPSWT; 40BP-N1-2 -
APRPHTSYSPLP; and 40BP-N1-3 - GMTAPPPPRLTQ) blocked CD40-CD154 interaction when
used at high concentrations. A consensus sequence (APxPPxxT) was conserved in
these three peptides. These peptides may constitute a useful and novel strategy
for the inhibition of the interaction between CD40 and CD154 molecules.
PMID- 17029107
TI - Gouty flexor tenosynovitis of the hand mimicking atypical mycobacterial
infection.
AB - A 50-year-old Japanese fish dealer presented with painful and swollen fingers.
Infectious flexor tenosynovitis with Mycobacterium marinum was suspected. Range
of motion was restored after tenosynovectomy and after ofloxacin and
clarithromycin were administered. Two years after the operation, the patient
presented again with acute inflammation in the same fingers. Histopathological
examination revealed gouty tenosynovitis. The preconception that mycobacterial
infection occurs often in fish dealers caused us to miss the correct diagnosis of
gouty tenosynovitis.
PMID- 17029108
TI - An external snapping hip caused by osteochondroma of the proximal femur.
AB - We herein report the findings of a 17-year-old boy who suffered from a right
external snapping hip, which was caused by an osteochondroma of the proximal
femur. He has been asymptomatic since the excision of the tumor. This case shows
a rare etiology in which an external snapping hip occurred between the iliotibal
band and the osteochondroma.
PMID- 17029109
TI - A case of Epstein-Barr virus-associated natural killer/T-cell lymphoma presenting
as dermatomyositis: extranodal relapse after 7 years in remission.
AB - A 56-year-old Japanese man was admitted to our hospital due to a fever of unknown
origin. He had had a history of extranodal natural killer (NK)/T-cell lymphoma,
nasal type, and had been in complete remission for 7 years until June 2003, when
he developed high fever, eyelid swelling, and muscular weakness. Serum creatine
kinase levels were elevated. Histopathological examination of skin and muscle
biopsy specimens revealed subcutaneous infiltration of lymphoid cells positive
for CD3, CD56, and Epstein-Barr virus-encoded small nuclear RNA-1. We report this
unique case of Epstein-Barr virus-associated lymphoma mimicking dermatomyositis.
PMID- 17029110
TI - A case of systemic lupus erythematosus complicated with pneumatosis cystoides
intestinalis.
AB - Pneumatosis cystoides intestinalis (PCI), which is characterized by the presence
of multiple gas-filled mucosal, submucosal, or subserosal cysts located
throughout the colon and/or small intestine, is an unusual complication of
systemic lupus erythematosus (SLE). We report a case of a 33-year-old woman with
a 5-year history of SLE with PCI. Her symptoms improved with conservative
management. Although PCI is a rare manifestation of SLE, clinicians should be
alert to the differential diagnosis of this complication.
PMID- 17029111
TI - Beneficial effect of complementary alternative medicine on lymphedema with
rheumatoid arthritis.
AB - Lymphedema of the limbs can be an added complication in a small number of
rheumatoid arthritis cases, becoming a long-standing problem even when there is
good control of inflammatory joint disease. In the present article, we describe a
patient with RA who developed lymph-edema of the forearms successfully treated
with TJ-48 (Juzentaihoto) as a complementary alternative medicine (CAM). This
kind of edema does not seem to show any consistent relationship with the severity
of arthritis in the literature surveyed. In contrast, lymphedema in this case
improved in parallel with RA disease activity. We discuss the utility of CAM
treatments and review the literature.
PMID- 17029112
TI - Asynchronous progressive diaphyseal dysplasia.
AB - We report the case of a 42-year-old Japanese woman with unusual diaphyseal
dysplasia of bilateral femora. Radiographs showed thickening and sclerosis of the
cortex with resultant enlargement of the diaphysis, unclear demarcation of the
surface of the cortex, and no periosteal reaction. These changes were found on
the left femur at the first presentation, and those on the right femur developed
within several years. Although this patient partly presented characteristics of
Ribbing disease and Camurati-Engelmann disease, the focal involvement of
bilateral femora suggested an unknown pathogenesis.
PMID- 17029113
TI - Rheumatoid arthritis-associated corneal ulceration complicated by bacterial
infection.
AB - We report two cases of rheumatoid ocular disease complicated by infection of
methicillin-sensitive Staphylococcus aureus (MSSA) in one case, and methicillin
resistant Staphylococcus aureus (MRSA) in the other. In both cases, punctal
occlusion and immunosuppressive therapy were presumed to be major risk factors of
the infections. In addition, the characteristic feature was corneal melting,
which is probably accelerated by infection. To avoid infectious progression and
melting, potent antibiotics followed by immunosuppressive therapy were necessary.
PMID- 17029114
TI - Lack of relationship between mannose-binding lectin variant alleles and risk of
arterial thrombosis in Japanese patients with systemic lupus erythematosus.
PMID- 17029115
TI - Apoptosis and cerebral ischemic reperfusion injury developed after haemorrhagic
shock: experimental study.
AB - BACKGROUND: Apoptosis is a process of programmed cell death that plays a role in
some normal and pathological conditions. In this study, we investigated the
apoptosis during cerebral ischemic reperfusion injury in response to haemorrhagic
shock in a rat model. METHODS: Thirty-six adult Sprague-Dawley rats were divided
into six groups: control, haemorrhagic shock (HS), ischemic reperfusion (IR), 1st
hour IR, 3rd hour IR, 6th hour IR and 24th hour IR. Rats were sacrificed by
taking blood from intracardiac area after finishing the experiment. The tissues
were fixed using neutral buffered 10% formaldehyde solution for histopathological
examination. Tissues were stained immunohistochemically with APO 2.7 and positive
expression apoptotic cells were counted using a Clemex Vision Lite 3.5 vision
analysis system. RESULTS: There were 2-3 apoptotic cells in the control group
(group 1) and this number increased to 8-11 in the haemorrhagic shock group
(group 2) (p<0.05). Secondary or more serious injury occurs during ischemic
reperfusion injury. The number of apoptotic cells increased to 11-14 at the 1st
hour (group 3) and it was significant as compared to group 2 (p<0.05). The number
of apoptotic cells significantly increased to 15-17 by the 3rd hour (group 4) as
compared to group 3 (p<0.05). While there was no additional increase by the end
of the 6th hour (group 5) as compared to group 4, the number of apoptotic cells
significantly increased to 18-24 by the end of 24th hour (group 6) as compared to
group 5 (p<0.05). CONCLUSION: The majority of injuries to the brain following
haemorrhagic shock occur during ischemic reperfusion. We observed that apoptosis
increases step by step on the 1st, 3rd and 24th hours after ischemic reperfusion
injury.
PMID- 17029116
TI - Bone marrow-derived osteoblasts seeded into porous beta-tricalcium phosphate to
repair segmental defect in canine's mandibula.
AB - BACKGROUND: Bone regeneration is often needed for many aesthetic and
reconstructive procedures. Tissue engineering provided a promising approach to
supplement existing treatment strategies. In this study, we aimed to evaluate the
effect of reconstructing mandibular defect by using bioceramics seeded with bone
marrow derived osteoblasts. METHODS: Canine's autologous marrow stromal cells
were Culture-expanded and induced to osteoblastic phenotype, then were seeded
into prepared porous beta-tricalcium phosphate, after being incubated in vitro.
The cell/ scaffold complexes were implanted into the prepared defect in canines'
mandibula and fixed by internal rigid fixation. In control groups, beta
tricalcium phosphate alone and autologous iliums were implanted into the prepared
defects. Twelve weeks after implantation, the specimens were examined
macroscopically and histologically. RESULTS: In experimental group and autologous
iliums group, new bone grafts were successfully developed at 12 weeks after
implantation and repaired the continuity of the mandibula. Histologically, newly
formed bone could be observed on the surface and in the pores of beta-tricalcium
phosphate in the cell/scaffold group, whereas incomplete bone repair was found in
pure beta-tricalcium phosphate group. CONCLUSION: The harvested bone marrow
derived osteoblasts possess the ability to form new bone tissue when seeded onto
porous beta-tricalcium phosphate, which shows the potential of using this method
to repair large segmental mandibular defect clinically.
PMID- 17029117
TI - The efficacy and immunogenicity of Pneumo-23 and ACT-HIB in patients undergoing
splenectomy.
AB - BACKGROUND: The objective of this prospective study is to validate the efficiency
of Streptococcus pneumoniae and Haemophilus influenzae vaccines in splenectomized
patients via the demonstration of seroconversion and uninterrupted ability for
opsonization. METHODS: Thirty-two adult patients (18 males, 14 females; mean age
46.1 years; range 18 to 79 years) who underwent elective or urgent splenectomy
for various benign and malignant hematological disorders, splenic trauma and
splenic masses were reviewed. Pneumo-23 and Act-HIB were administered to all
patients on routine basis. In order to demonstrate the ongoing opsonizing
capacity of the immune system and the seroconversion of immunoglobulins after
vaccination, antibody titers of IgG and IgM and plasma C3 and C4 levels were
quantitatively measured. RESULTS: The operative morbidity was 9% and overall
mortality was 16%, with no early postoperative death in this series. Five
patients with various malignant disorders died due to dissemination of their
primary tumor. None of the patients with benign hematological disorders or those
with splenic trauma died during the mean follow-up of 427 days. Furthermore,
death from overwhelming postsplenectomy infection was nil in our clinical survey.
All of the patients including those with malignancy had normal IgG (mean: 1383.1
mg/dL) and IgM levels (mean: 80.9 mg/dL) during discharge and at the last follow
up. Among the patients with benign hematological disorders, splenic trauma and
splenic masses necessitating splenectomy, C3 and C4 levels were entirely within
normal limits with a mean of 108.8 mg/dL and 21.4 mg/dL, respectively.
CONCLUSION: This preliminary study reveals adequate seroconversion of
immunoglobulins in all patients and normal C3 and C4 levels in patients with
benign hematological disorders and splenic trauma. Moreover, none of the patients
in the latter group had S. pneumoniae or H. influenzae infection nor did they
expire due to overwhelming sepsis during the follow-up period. Long-term follow
up is required to determine the continuation of this immunologic response and the
necessity of repeated vaccination.
PMID- 17029118
TI - [The use of the laryngeal mask airway and the cuffed oropharyngeal airway during
percutaneous tracheostomy].
AB - BACKGROUND: The aim of our study is to compare the safety and efficiency of the
use of the laryngeal mask airway (LMA) and the cuffed oropharyngeal airway (COPA)
with the use of endotracheal tube (ETT) for maintain patent airway during
percutaneous tracheostomy (PCT). METHODS: The patients were randomly assigned to
LMA group (n=35, M/F; 28/7, age; 52 [18-79]), COPA group (n=31, M/F; 23/8, age;
57 [18-80]) and ETT group (n=30, M/F; 22/8, age; 49 [18-80]) with respect to use
of LMA, COPA and ETT in order to maintain patent airway during PCT procedure. PT
was performed as described by Griggs et al. Complications occurred during and
after PCT procedure and airway manipulations required to maintain a patent airway
were recorded. RESULTS: Duration of PT was longer in the ETT group comparing with
the other groups (for both groups; p<0.01). The LMA failed to maintain patent
airway in 1 of 35 patients (2.9%) and the COPA failed to maintain patent airway
in 3 of 31 patients (9.7%). The airway intervention required to maintain patent
airway was found to be higher in the COPA group (45.2%) than in the LMA group
(11.4%) (p<0.01). There was no significant difference with respect to the
complications between the groups. CONCLUSION: In our study, LMA and COPA were
inserted easily during PCT with high success rates, but airway manipulations were
higher in the COPA group. In our opinion, supra/infraglottic airway devices to
maintain patent airway during PCT should be chosen according to patient's status
and physician's experience.
PMID- 17029119
TI - [The effects of informing patients and their relatives on satisfaction at
emergency units].
AB - BACKGROUND: The research was performed to determine the effect of adding a
service unit planned to be carried out by nurses into the current emergency work
flow on the patient satisfaction. METHODS: The research was carried out on 300
patients who were discharged from an University Hospital Emergency Department in
Turkey between 21 January 2002 and 22 March 2002. The data of the research were
collected by using Patient Identification Form, Nurse Activity Form, The
Evaluation Form for Service of Giving Information and Patient Follow-up Form. The
patients were informed by the information booklet developed by the researcher,
their questions were answered and a copy of the information booklet was given to
the patients and/or their families. The patients were called from their homes or
offices one week after their discharge from the hospital and their satisfaction
levels of the information given by the researcher were questioned. The data
collected from the research were analyzed in computer by using percentage, chi
square and the significance test for universe rate. RESULTS: It was determined
that the level of patient satisfaction was increased when the information was
given together with the booklet about their diseases, treatments and the cares
and it was also understood that calling the patients to be followed was
essential. CONCLUSION: It is suggested that the informations should be given to
the patients and their relatives on discharge by the nurses and new information
booklets should be developed.
PMID- 17029120
TI - [The evaluation of bicycle accidents that were admitted to a pediatric emergency
department].
AB - BACKGROUND: We planned this study to evaluate trauma cases secondary to bicycle
driving in childhood and to draw attention to the importance of the regulation of
traffic rules, the education of bicycle drivers, and the importance of helmet
usage. METHODS: Data in this study were obtained by retrospective review of the
files of trauma cases admitted to the Pediatric Emergency Unit of Trakya
University Medical Faculty between January 2003 and August 2005. Patients' age,
gender, clinical signs, type of injury, season of the event and percentage of
hospitalization were obtained from hospital records. RESULTS: Fifteen (24.6%) of
61 cases who were admitted to our emergency unit were females and 46 (75.4%) were
males. The types of trauma of all patients who suffered from bicycle accidents
were as following: 42 (68.9%) head trauma, 29 (47.5%) extremity trauma, 49
(80.3%) soft tissue trauma, 2 (3.3%) abdominal trauma, and one case of urogenital
trauma. Also multiple traumas were present in most of these cases. Thirteen
patients had extremity fractures and three had cranial fractures. None of the
bicycle drivers were using helmets at the time of the trauma. CONCLUSION: Bicycle
drivers should have specific education, helmet use must become widespread and
special traffic regulations have to be settled.
PMID- 17029122
TI - Conservative management of a grade V renal trauma associated with a grade III
hepatic lesion: is it possible?
AB - Conservative management of solid abdominal organ injuries has been increasing and
challenging trauma surgeons. This case report describes a successful non
operative management of a grade V renal lesion associated to a grade III hepatic
lesion. Such lesions have not been described in conjunction in the revised
literature.
PMID- 17029121
TI - [The factors affecting the morbidity and mortality in chest trauma].
AB - BACKGROUND: We evaluated thoracic trauma cases with respect to etiologic causes,
other system injuries accompanying to the thoracic trauma, treatment methods and
outcomes and the prognostic factors affecting the need for thoracotomy, length of
hospital stay, morbidity and mortality in the light of relevant literature data.
METHODS: A retrospective evaluation was performed on 141 patients (102 males
(72.3%), 39 females (27.7%); mean age 40; range 8 to 89 years) who were treated
for thoracic trauma in our center between July 2003 and December 2005. RESULTS:
117 patients (83%) had blunt and 24 (17%) penetrating thoracic trauma. Isolated
thoracic trauma and multisystem trauma were found in 48 (34%) and 93 (66%)
patients, respectively. Mean white blood cell count was 12.560+/-5.7 (5-25 x 103
/uL) at admission. The number of patients who met lung injury scale criteria for
grade I, grade II, grade III and grade IV were 19 (13.5%), 12 (8.5%), 25 (17.7%)
and 13 (9.2%), respectively. Hypotension was determined in 16 patients (11.3%)
during admission. With regard to treatment, while symptomatic conservative
management was satisfactory in 76 patients (53.9%), tube thoracoscopy and
thoracotomy were performed in 59 (41.8%) and 11 (7.8%) patients respectively. The
morbidity was seen in 30 patients (21.3%). The mortality rate was 7.8% (n=11).
CONCLUSION: The high white blood cell count, high lung injury scale grade, 3 and
more rib fractures and accompanying head injury were determined as the prognostic
factors affecting the morbidity and mortality.
PMID- 17029123
TI - [Pneumatosis intestinalis mimicking free intraabdominal air: a case report].
AB - A 47-year-old male patient had undergone endoscopic balloon dilatation six times
due to pyloric stenosis however the result was not satisfying. Surgical treatment
was considered. Chest X-ray revealed free sub-diaphragmatic air but there were no
acute abdomen signs clinically. In abdominal computerized tomography, there were
small intestinal loops anterior to the liver and there was gas collection, which
can not be differentiated exactly between an extraluminal free air and the one in
the bowel wall of adjacent small bowel segments. In the emergency surgery cysts
filled with gas in the wall of distal ileal segments were seen. Pneumatosis
intestinalis should be kept in mind in the differential diagnosis of free
intraabdominal air.
PMID- 17029124
TI - [Traumatic aneurysm of the superficial temporal artery: a case report].
AB - Traumatic aneurysm of superficial temporal artery is an uncommon lesion. Blunt
traumas of war, firearm, motorized vehicle and sport injuries are common causes.
In this case, traumatic aneurysm of superficial temporal artery that occurs after
scalp trauma in 74 years old male patient, was reported. Patient who suffers from
a mass in his forehead ten days after trauma was admitted to our clinic.
Selective angiography of the right temporal artery was performed as traumatic
aneurysm was suspected upon the findings of physical examination and cranial
computerized tomography studies. The aneurysm was detected. The proximal and
distal part of the aneurysm was ligated and it was totally removed under general
anesthesia. The histopathological investigation confirmed the presence of the
traumatic aneurysm. Especially in hairy skin injuries, traumatic lesions should
be considered as an aneurysm. Diagnosis, treatment, and surgical strategy must be
planned by the help of these informations.
PMID- 17029125
TI - [Longitudinal clival fractures: a report of three cases].
AB - Fractures of the clivus are often associated with severe head trauma and have
high mortality rates due to coexisting injury of the adjacent vessels, brain stem
and lower cranial nerves. An early diagnosis is often not possible because of
adherent problems, high mortality rate and inadequacy of emergency imaging.
Diagnosis has recently become easier with high resolution bone window computed
tomography studies. In this study, radiological and clinical findings of three
patients with longitudinal clival fractures and severe head trauma have been
presented and associated injuries and prognostic issues are discussed with
reference to the limited number of similar cases in the English literature.
PMID- 17029126
TI - Survival of an eight-year-old child with a very severe high-tension electrical
burn injury: a case report.
AB - We present the management and survival of an eight-year-old boy with a severe
high-tension electrical burn injury of 68% of total body surface area in a
surgical intensive care unit, as a result of a well-planned and applied treatment
strategy. Subsequent to escharotomy and fasciotomy operations under general
anesthesia, the patient was taken into the surgical intensive care unit. In
addition, patient underwent nine more operations including right femur
disarticulation and split-thickness skin graftings with homografts from his
brother and autografts. The patient was connected to mechanical ventilator for 59
days. By the time the patient was transferred to plastic and reconstructive
surgery ward, he was fully conscious, cooperated and hemodynamically stable.
PMID- 17029127
TI - Outbreak of cutaneous Rhizopus arrhizus infection associated with karaya ostomy
bags.
AB - BACKGROUND: We investigated an outbreak involving 2 patients hospitalized at
hospital A with cutaneous Rhizopus arrhizus (oryzae) infections of surgically
created stomas. METHODS: A cohort study involving all patients having ileostomy
or colostomy surgery during the outbreak period (January-April 2005) was
performed. Environmental samples, including samples obtained from nonsterile
karaya (a plant-derived adhesive) ostomy bags and from select hospital areas,
were collected. A point prevalence survey was conducted at 5 unrelated hospitals
to assess stoma care practices and mold contamination of karaya ostomy bags
outside of hospital A. Zygomycete isolates were identified by standard methods.
RESULTS: Infections occurred 7 and 10 days after operations for the 2 patients; 1
patient died. In a 21-patient cohort, receiving the equivalent of > or =0.5 mg/kg
per day of prednisone during the week prior to the index date was associated with
infection (infection rate, 33% for patients receiving > or =0.5 mg/kg per day of
prednisone vs. 0% for patients receiving <0.5 mg/kg per day of prednisone;
P=.07). The time to first ostomy bag change was longer for patients with
infection (median duration, 8.5 days; range, 7-10 days) than for the 19 patients
without infection (median duration, 1.5 days; range, 1-17 days; P=.08). At
unrelated hospitals, the median time to first ostomy bag change was 2 days
(range, 1-6 days) for 18 patients after ostomy. R. arrhizus was recovered from 10
of 18 karaya ostomy bags from hospital A and from karaya ostomy bags donated from
3 of 5 other hospitals, but it was not recovered from the hospital A environment.
CONCLUSIONS: The initial karaya ostomy bag was likely to be the source of
Rhizopus infection, and prolonged exposure before the first ostomy bag change
might have precipitated infection in these susceptible individuals. Karaya might
contain opportunistic molds that can pose an infectious risk among susceptible
persons.
PMID- 17029128
TI - No effect of pyridoxine on the incidence of myelosuppression during prolonged
linezolid treatment.
AB - Complications of long-term linezolid administration include anemia and
thrombocytopenia. A recent report has suggested that pyridoxine may prevent
myelosuppression. Pyridoxine was administered to 24 patients with bone infections
who were being treated with linezolid. Thrombocytopenia occurred in 11 patients
(45.8%), and anemia occurred in 6 (25%). We concluded that treatment wtih
pyridoxine is unlikely to benefit patients who have been receiving linezolid for
>2 weeks.
PMID- 17029129
TI - Progression of Pneumocystis jiroveci pneumonia in patients receiving echinocandin
therapy.
AB - Echinocandins are a novel class of antifungal drugs that target beta (1, 3)-D
glucan synthesis. Animal studies have shown that these agents have activity
against Pneumocystis jiroveci infection; however, clinical data are lacking. We
reviewed all cases of proven P. jiroveci pneumonia (PCP) in non-human
immunodeficiency virus-infected patients at our hospital over a 5 year period
(2001-2005). Two patients received conventional PCP treatment and concomitant use
of echinocandins for presumed invasive aspergillus. In both cases, PCP
progressed, and the patient died. The use of echinocandins in the prevention or
treatment of PCP cannot be recommended without evidence to support their
effectiveness.
PMID- 17029130
TI - The clinical assessment, treatment, and prevention of lyme disease, human
granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the
Infectious Diseases Society of America.
AB - Evidence-based guidelines for the management of patients with Lyme disease, human
granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis),
and babesiosis were prepared by an expert panel of the Infectious Diseases
Society of America. These updated guidelines replace the previous treatment
guidelines published in 2000 (Clin Infect Dis 2000; 31[Suppl 1]:1-14). The
guidelines are intended for use by health care providers who care for patients
who either have these infections or may be at risk for them. For each of these
Ixodes tickborne infections, information is provided about prevention,
epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the
doses and durations of antimicrobial therapy recommended for treatment and
prevention of Lyme disease and provide a partial list of therapies to be avoided.
A definition of post-Lyme disease syndrome is proposed.
PMID- 17029131
TI - Safety and immunogenicity of nonadjuvanted and MF59-adjuvanted influenza A/H9N2
vaccine preparations.
AB - BACKGROUND: Influenza A/H9N2 viruses can infect humans and are considered to be a
pandemic threat. Effective vaccines are needed for these and other avian
influenza viruses. METHODS: We performed a phase I, randomized, double-blind
trial to evaluate the safety and immunogenicity of a 2-dose schedule
(administered on days 0 and 28) of 4 dose levels (3.75, 7.5, 15, and 30 microg of
hemagglutinin) of inactivated influenza A/chicken/Hong Kong/G9/97 (H9N2) vaccine
with and without MF59 adjuvant. Vaccine safety was assessed with a diary and
selected blood tests. Immunogenicity was measured using serum hemagglutination
inhibition (HAI) and microneutralization (MNt) antibody assays. RESULTS. Ninety
six healthy adults (age, 18-34 years) were enrolled in the study. Arm discomfort
was more common in groups that received adjuvant, but adverse effects of the
vaccination were generally mild. Geometric mean serum HAI and MNt antibody titers
to the influenza A/chicken/Hong Kong/G9/97 (H9N2) virus strain for all vaccine
groups were similar on day 0 but were significantly higher (P<.001) on both days
28 and 56 for the MF59-adjuvanted vaccine groups than for groups given
nonadjuvanted vaccine. Other measures of immunogenicity were also higher in the
adjuvanted vaccine groups. HAI and MNt geometric mean titers measured after the
administration of a single dose of MF59-adjuvanted vaccine were similar to those
measured after 2 doses of nonadjuvanted vaccine. CONCLUSIONS: The combination of
MF59 adjuvant with a subunit vaccine was associated with improved immune
responses to an influenza A/H9N2 virus. The adjuvanted vaccine was immunogenic
even after a single dose, raising the possibility that a 1-dose vaccination
strategy may be attainable with the use of adjuvanted vaccine.
PMID- 17029132
TI - Seroprevalence of cytomegalovirus infection in the United States, 1988-1994.
AB - BACKGROUND: Cytomegalovirus (CMV) is a leading cause of congenital illness and
disability, including hearing loss and mental retardation. However, there are no
nationwide estimates of CMV seroprevalence among pregnant women or the overall
population of the United States. METHODS: To determine CMV prevalence in a
representative sample of the US population, we tested serum samples for CMV
specific immunoglobulin G from participants aged > or =6 years (n=21,639) in the
third National Health and Nutrition Examination Survey (1988-1994). RESULTS: The
prevalence of CMV infection was 58.9% in individuals > or =6 years old. CMV
seroprevalence increased gradually with age, from 36.3% in 6-11-year-olds to
90.8% in those aged > or =80 years. CMV seroprevalence differed by race and/or
ethnicity as follows: 51.2% in non-Hispanic white persons, 75.8% in non-Hispanic
black persons, and 81.7% in Mexican Americans. Racial and/or ethnic differences
in CMV seroprevalence persisted when controlling for household income level,
education, marital status, area of residence, census region, family size, country
of birth, and type of medical insurance. Among women, racial and/or ethnic
differences were especially significant; between ages 10-14 years and 20-24
years, seroprevalence increased 38% for non-Hispanic black persons, 7% for non
Hispanic white persons, and <1% for Mexican Americans. CONCLUSIONS: On the basis
of these results, we estimate that each year in the United States approximately
340,000 non-Hispanic white persons, 130,000 non-Hispanic black persons, and
50,000 Mexican American women of childbearing age experience a primary CMV
infection. Given the number of women at risk and the significance of congenital
disease, development of programs for the prevention of CMV infection, such as
vaccination or education, is of considerable public health importance.
PMID- 17029133
TI - Cytomegalovirus infection: back to the future or no more elephants?
PMID- 17029134
TI - Risk factors and outcome among a large patient cohort with community-acquired
acute hepatitis C in Italy.
AB - BACKGROUND: The epidemiology of acute hepatitis C has changed during the past
decade in Western countries. Acute HCV infection has a high rate of chronicity,
but it is unclear when patients with acute infection should be treated. METHODS:
To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and
to assess the rate of and factors associated with chronic infection, we enrolled
214 consecutive patients with newly acquired hepatitis C during 1999-2004. The
patients were from 12 health care centers throughout the country, and they were
followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver
tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146
patients (68%) had symptomatic disease. The most common risk factors for
acquiring hepatitis C that were reported were intravenous drug use and medical
procedures. The proportion of subjects with spontaneous resolution of infection
was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days
(range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting
hepatitis experienced HCV RNA clearance within 3 months of disease onset.
Multiple logistic regression analyses showed that none of the variables
considered (including asymptomatic disease) were associated with increased risk
of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the
importance of medical procedures as risk factors in the current spread of HCV
infection in Italy. Because nearly all patients with acute, self-limiting
hepatitis C--both symptomatic and asymptomatic--have spontaneous viral clearance
within 3 months of disease onset, it seems reasonable to start treatment after
this time period ends to avoid costly and useless treatment.
PMID- 17029135
TI - Shiga toxin activatable by intestinal mucus in Escherichia coli isolated from
humans: predictor for a severe clinical outcome.
AB - BACKGROUND: Some Escherichia coli produce Shiga toxin (Stx) in which cytotoxicity
is increased (activated) by intestinal mucus and elastase (Stx2d(activatable)).
These strains are highly virulent in mice, but their association with human
disease is poorly understood. We investigated the prevalence of
Stx2d(activatable) among Stx-producing E. coli (STEC) isolated from humans and
the association between production of this Stx and the clinical outcome of
infection. METHODS: A total of 922 STEC isolates obtained from patients with
hemolytic uremic syndrome or bloody or nonbloody diarrhea or from asymptomatic
carriers were tested for the gene encoding Stx2d(activatable) by PCR and PstI
restriction analysis. The toxin activatibility by human and mouse intestinal
mucus and by an elastase was determined by quantifying the cytotoxicity using the
Vero cell assay. RESULTS: The stx(2d-activatable) gene was identified in 60
(6.5%) of 922 STEC strains; in 31 of these strains, it was the sole stx gene.
Thirty of these 31 strains produced Stx2d(activatable). All of them lacked the
intimin-encoding eae gene. Among eae-negative STEC, which typically cause mild
diarrhea or asymptomatic infection, production of Stx2d(activatable) was
significantly associated with the ability to cause severe disease, including
bloody diarrhea (P<.001), and with systemic complications, such as hemolytic
uremic syndrome (P<.001). CONCLUSIONS: Production of Stx2d(activatable) by the
infecting STEC may predict a severe clinical outcome of the infection, with
progression to hemolytic uremic syndrome. A prompt and comprehensive subtyping of
stx genes in STEC isolates is necessary to alert the treating physician that a
patient is at risk of developing hemolytic uremic syndrome, even though the
infecting STEC lacks eae.
PMID- 17029136
TI - What makes an enterohemorrhagic Escherichia coli?
PMID- 17029137
TI - Absence of efficacy of nonviable Lactobacillus acidophilus for the prevention of
traveler's diarrhea: a randomized, double-blind, controlled study.
AB - BACKGROUND: Diarrhea is the most common illness associated with international
tourism. We evaluated the efficacy of a probiotic preparation of nonviable
Lactobacillus acidophilus (hereafter referred to as LA) for the prevention of
traveler's diarrhea. METHODS: We conducted a randomized, double-blind, controlled
trial. Travelers were randomized to receive either LA or placebo twice daily from
1 day before their departure to 3 days after their return. On each day of the
trip and the week following the return, travelers had to record the number and
consistency of stools and their adherence to the treatment. Diarrhea was defined
as > or =3 unformed stools in a 24-h period. RESULTS: From January 2001 to
September 2004, a total of 174 subjects were randomized to each treatment group.
Half of the travelers went to West Africa, and organized tours or backpacking
were the most common modes of traveling. The incidence of diarrhea did not differ
between the 2 groups; it was 61.4 cases per 100 person-months in the LA group
(95% confidence interval [CI], 44.1-85.5) and 43.4 cases per 100 person-months in
the placebo group (95% CI, 30.0-62.9) (P=.14). Adjustment for travel duration and
other variables did not reveal any difference between the 2 groups (adjusted
hazard ratios comparing the LA and placebo groups were 1.43 [95% CI, 0.87-2.36]
in an intent-to-treat analysis and 1.38 [95% CI, 0.79-2.39] in an efficacy
analysis). CONCLUSIONS: There was no beneficial effect of treatment with LA for
the prevention of travelers' diarrhea. More studies are required to assess the
efficacy of other specific probiotics (e.g., a Lactobacillus rhamnosus GG
preparation) for preventing traveler's diarrhea.
PMID- 17029138
TI - An elderly woman with abdominal pain and Fever.
PMID- 17029139
TI - VisualDx: decision-support software for the diagnosis and management of
dermatologic disorders.
AB - The VisualDx system (http://www.logicalimages.com/prodVDx.htm) is a JAVA-based
decision-support program developed by Logical Images to be used in clinical care
to develop differential diagnoses based upon morphologic finding- and patient
finding-driven searching. It consists of several modules, many of which are very
relevant to infectious diseases specialists, such as Fever & Rash; International
Travel; Drug Eruptions; Smallpox Vaccination; Terrorism Recognition;
Immunocompromised, HIV or AIDS; Female Genital Rashes & Growths; and Male Genital
Rashes & Growths. Unlike books and atlases indexed by disease, with VisualDx,
clinicians can enter patient descriptors and lesion morphologies, resulting in
rapid assistance with differential diagnosis. VisualDx also increases clinician
awareness of, knowledge about, and skills in the recognition of chemical warfare,
bioterrorism, and radiation injuries.
PMID- 17029140
TI - Illness in travelers visiting friends and relatives: a review of the GeoSentinel
Surveillance Network.
AB - Travelers returning to their country of origin to visit friends and relatives
(VFRs) have increased risk of travel-related health problems. We examined
GeoSentinel data to compare travel characteristics and illnesses acquired by 3
groups of travelers to low-income countries: VFRs who had originally been
immigrants (immigrant VFRs), VFRs who had not originally been immigrants
(traveler VFRs), and tourist travelers. Immigrant VFRs were predominantly male,
had a higher mean age, and disproportionately required treatment as inpatients.
Only 16% of immigrant VFRs sought pretravel medical advice. Proportionately more
immigrant VFRs visited sub-Saharan Africa and traveled for >30 days, whereas
tourist travelers more often traveled to Asia. Systemic febrile illnesses
(including malaria), nondiarrheal intestinal parasitic infections, respiratory
syndromes, tuberculosis, and sexually transmitted diseases were more commonly
diagnosed among immigrant VFRs, whereas acute diarrhea was comparatively less
frequent. Immigrant VFRs and traveler VFRs had different demographic
characteristics and types of travel-related illnesses. A greater proportion of
immigrant VFRs presented with serious, potentially preventable travel-related
illnesses than did tourist travelers.
PMID- 17029141
TI - Recurrent benign lymphocytic meningitis.
AB - Recurrent benign lymphocytic meningitis is a recurring, typically innocuous,
painful form of aseptic meningitis. This syndrome is associated with transient
neurological symptoms in one-half of afflicted patients. The causative agent is
usually herpes simplex virus type 2, which can be confirmed by detection of viral
DNA in the cerebrospinal fluid using polymerase chain reaction. Clinical disease
resolves spontaneously; however, acyclovir, valacyclovir, and famciclovir have
been administered to some patients for both episodic therapy and suppression of
recurrences. This therapy is thought to be beneficial, although there is no
controlled trial data to support efficacy and safety.
PMID- 17029142
TI - HIV-associated monoclonal gammopathy: a retrospective analysis of 25 patients.
AB - BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is unusual
in the general population aged <60 years. Various reports indicate a much higher
incidence of monoclonal gammopathy among human immunodeficiency virus (HIV)
infected patients and a significantly younger age at diagnosis. We sought to
describe the laboratory findings and clinical course of MGUS, including
association with plasma cell disorders, other malignancies, and infections, in 25
HIV-infected patients with a detectable serum monoclonal protein. METHODS: We
reviewed the patients' demographic characteristics, stage of HIV infection, and
clinical course. Laboratory studies included determination of CD4(+) T lymphocyte
cell counts, HIV type 1 loads, and quantitative immunoglobulin levels; serum and
urine protein immunoelectrophoresis; and determination of serum viscosity
indices. Skeletal surveys and bone marrow biopsies were performed in selected
cases. RESULTS: Twenty-four of 25 patients were male, and the median age of
patients was 50 years (range, 21-69 years). The median CD4(+) T lymphocyte count
was 350 cells/ microL (range, 40-1029 cells/ microL; mean, 355 cells/ microL),
and the median HIV load was <75 copies/mL (range, <50 to 100,000 copies/mL; mean,
20,800 copies/mL). Thirteen of 25 patients had HIV viremia, despite receiving
highly active antiretroviral therapy (HAART). After a mean follow-up duration of
21 months, 7 patients (28%) received a diagnosis of a malignancy (multiple
myeloma, in 1 patient; non-Hodgkin lymphoma, in 1; Hodgkin lymphoma, in 1; Kaposi
sarcoma, in 2; and plasmacytoma, in 2). Ten patients were coinfected with
hepatitis B virus and/or hepatitis C virus; 6 were anemic. No patients developed
renal failure or hypercalcemia. Nine (56%) of 19 evaluable patients had a
decrease of serum monoclonal protein (mean, 0.5 g/dL) while receiving HAART.
CONCLUSIONS: Patients in our study were characterized by the detection of a
monoclonal protein at a younger age and the increased presence of other viral
infections (infection with hepatitis B or C virus or Kaposi sarcoma herpesvirus)
than is typically seen in an HIV-uninfected cohort. CD4(+) T lymphocyte counts
were relatively robust. HAART appeared to have a favorable impact on the serum
monoclonal protein level in 9 patients. Long-term follow-up is needed to better
define the natural history of MGUS and the link to other possible contributing
factors.
PMID- 17029143
TI - Monoclonal gammopathy associated with HIV infection.
PMID- 17029144
TI - Coinfection with hepatitis C virus increases lymphocyte apoptosis in HIV-infected
patients.
AB - To test the role of hepatitis C virus (HCV) in CD4 cell depletion in human
immunodeficiency virus (HIV)-coinfected patients, T cell apoptosis was measured
by annexin V labeling in 31 HIV-infected and 30 HIV-HCV-coinfected patients who
were not receiving antiretroviral therapy. Apoptosis in naive CD4(+) T cells and
in naive and memory CD8(+) T cells was significantly higher in HIV-HCV-coinfected
than in monoinfected patients.
PMID- 17029145
TI - John McFadyean and the centenary of the first isolation of Campylobacter species.
AB - Campylobacter species recently emerged as a leading cause of acute diarrhea in
humans, but it is not generally known that these species were first cultured from
samples from aborting ewes as far back as 1906. This took place in the United
Kingdom during a study that spanned several years of epizootic abortion in cattle
and sheep. The chief investigator in this major undertaking was John McFadyean, a
little-known yet remarkable man who founded veterinary pathology in Britain and
who made immense contributions to public health. A brief portrayal illustrates
his uncompromising dedication to scientific accuracy and to his profession, often
in the face of opposition.
PMID- 17029148
TI - Meta-analysis of diagnostic test accuracy.
PMID- 17029149
TI - Randomized, controlled trials of directly administered antiretroviral therapy for
HIV-infected patients: questions about study population and analytical approach.
PMID- 17029151
TI - Colonization or infection with multidrug-resistant Acinetobacter baumannii may be
an independent risk factor for increased mortality.
PMID- 17029152
TI - Antituberculosis therapy and imatinib for chronic myeloid leukemia.
PMID- 17029153
TI - Variant IS1016 insertion elements in invasive Haemophilus influenzae type b
isolates harboring multiple copies of the capsulation b locus.
PMID- 17029154
TI - Prevalence of influenza B during the 2004-2005 season in Japan.
PMID- 17029155
TI - In support of Dr. Thomas Butler.
PMID- 17029156
TI - Prevention of perioperative hypothermia with forced-air warming systems and upper
body blankets.
AB - Forced-air warming is known as an effective procedure in prevention and treatment
of perioperative hypothermia. Hypothermia is associated with disturbances of
coagulation, raises postoperative oxygen consumption by shivering, increases
cardiac morbidity, leads to a higher incidence of wound infection, and prolongs
hospital stay. Additionally, preoperative local warming reduces the incidence of
wound infection after clean surgery. In an animal experiment it has been
demonstrated that even during large abdominal operations the major source of heat
loss was the skin. Although evaporation accounted for the largest heat loss from
the abdominal cavity, it was a minor source due to the smaller heat losing area.
As a consequence, reduction of heat loss from the skin is the most promising
approach to avoid hypothermia. During abdominal surgery and lower-limb surgery,
the use of upper blankets is favourable. The use of upper-body blankets implies a
reduction of heat loss in a relevant area and, furthermore, a heat gain. The
covered area is approximately 0.35 m2, or approximately 15%-20% of body surface.
The heat balance in this area can be changed by 46.1W to 55.0W by forced-air
warming systems with upper body blankets. Depending on the surgical procedure and
resulting fluid demand, forced-air warming with upper-body blankets-in
combination with insulation and fluid warming-is an effective method to prevent
perioperative hypothermia.
PMID- 17029157
TI - Current status of laparoscopic ultrasound.
AB - The purpose of this chapter is to introduce the beginning surgeon
ultrasonographer to the use of ultrasound during laparoscopic surgery. The
authors routinely use ultrasound in the intraoperative, endoscopic, and office
settings. The importance of ultrasound in the various surgical specialties is
well documented in the literature. Since the introduction of minimally invasive
techniques to General Surgery, many advanced applications of ultrasonography have
been developed. Confident examinations of intraabdominal anatomy, pathologic
conditions, and therapeutic procedures can readily be performed. In this chapter,
a comprehensive introduction to laparoscopic ultrasound is presented to the
practicing General Surgeon. The basic equipment requirements and setup are
explained. Fundamental techniques of laparoscopic ultrasound examination are
described. The authors' method of screening for common bile duct stones during
routine laparoscopic cholecystectomy is illustrated. Examination of the normal
biliary tree with helpful hints is presented. The authors' systematic technique
of visualizing the normal liver parenchyma is described. Common benign and
malignant findings are elucidated. A brief synopsis of pancreatic ultrasonography
with attention to pathologic findings is provided. Uses of ultrasound in
unanticipated situations are introduced. With perseverance, the reader will
discover that laparoscopic ultrasound skills can be readily attained.
PMID- 17029158
TI - Diagnostic validity of radio-guided sentinel node mapping for gastric cancer: a
review of current status and future direction.
AB - Diagnostic validity of sentinel node (SN) mapping has been recently introduced
into the field of various solid tumors, including gastrointestinal (GI) cancer.
In gastric cancer, acceptable detection rates of SNs, as well as sensitivity in
detecting micrometastasis based on SN status, was reported using the dye-guided
method, as well as the radio-guided method. Gastric cancer is currently one of
the suitable targets of SN navigation surgery among visceral tumors. Despite the
multi-directional and complicated lymphatic flow from gastric mucosa, the
anatomical situation of the stomach is relatively suitable for SN mapping in
comparison with organs embedded in closed spaces, such as the esophagus and
rectum. In particular, clinically T1N0 gastric cancer seems to be a good entity
for which to try to modify the therapeutic approach. From the data reported in
the literature, micro-metastases tend to be limited within the sentinel basins in
cT1N0 gastric cancer. Sentinel basins are, therefore, good targets of selective
lymphadenectomy for cT1N0 gastric cancer with the potential risk of
micrometastasis. Furthermore, laparoscopic local resection is theoretically
feasible for curative treatment of SN negative early gastric cancer. For
laparoscopic application of SN mapping of gastric cancer, a radio-guided method
is essential. Although recent single institutional studies support the validity
of the SN concept, a multi-centric prospective validation study based on a
standardized protocol is essential for further clinical application. Currently,
two major well-designed clinical trials of SN mapping for gastric cancer open
surgery have been initiated in Japan. Radio-guided SN mapping for gastric cancer
has a great potential to provide a new paradigm shift for surgical management of
an early gastric cancer.
PMID- 17029159
TI - Management of intra-abdominal abscess due to surgical site infection.
AB - Intra-abdominal abscesses are one of the major complications that occur after
Gastrointestinal Surgery. Therapeutic modalities include drainage and irrigation.
This study describes the development of a new drainage and continuous irrigation
system that results in less skin irritation and reduced dressing changes. This
system involved the use of the Surgidrain open top (ALCARE, Tokyo, Japan), which
consists of a sealing sheet with a drainage lumen and plastic cap. A double-lumen
tube was inserted into the abscess cavity through a slit in the plastic cap. The
abscess cavity could, therefore, be irrigated continuously through one lumen of
the double-lumen tube, and most of the fluid could be drained through the second
lumen of the double-lumen tube. Overflow fluid was drained through the Surgidrain
open top drainage lumen. This system enabled better protection against skin
complications and the ability to easily flush the abscess intermittently.
PMID- 17029161
TI - Laparoscopic sleeve gastrectomy (LSG): review of a new bariatric procedure and
initial results.
AB - OBJECTIVE: To evaluate the outcomes and initial results of laparoscopic sleeve
gastrectomy (LSG) and review of the literature. METHODS: A retrospective analysis
of the initial ten patients who underwent LSG was performed. Study endpoints
included operative time, complication rates, hospital length of stay, and
percentage of excess body weight loss. RESULTS: This study included five women
and five men, with a mean age of 43 (range: 31-52) years. Their mean preoperative
weight was 182 kg (range: 125 kg-247 kg), with a mean preoperative body mass
index (BMI) of 64 (range: 61- 80). Indication for LSG was the importance of BMI
in all patients. One patient had previous restrictive bariatric surgery. Mean
operative time was two (range: 1.5-2.5) hours. No patients required conversion.
No postoperative complications nor mortality were noted. The median hospital stay
was 7.2 days. Average excess body weight loss and BMI at one year were 51% and 23
kg/m2, respectively. CONCLUSIONS: LSG can be integrated safely into a bariatric
treatment program with good results in terms of weight loss and quality of life.
LSG can be a first-step procedure before gastric bypass or duodenal switch, or a
one-step restrictive procedure if long-term results are good. LSG should be
considered as a surgical option in the bariatric field, but further studies are
needed to determine its exact use.
PMID- 17029160
TI - Clinical applications of commercially available video recording and monitoring
systems: inexpensive, high-quality video recording and monitoring systems for
endoscopy and microsurgery.
AB - The exclusive charge-coupled device (CCD) camera system for the endoscope and
electronic fiberscopes are in widespread use. However, both are usually
stationary in an office or examination room, and a wheeled cart is needed for
mobility. The total costs of the CCD camera system and electronic fiberscopy
system are at least US Dollars 10,000 and US Dollars 30,000, respectively.
Recently, the performance of audio and visual instruments has improved
dramatically, with a concomitant reduction in their cost. Commercially available
CCD video cameras with small monitors have become common. They provide excellent
image quality and are much smaller and less expensive than previous models. The
authors have developed adaptors for the popular mini-digital video (mini-DV)
camera. The camera also provides video and acoustic output signals; therefore,
the endoscopic images can be viewed on a large monitor simultaneously. The new
system (a mini-DV video camera and an adaptor) costs only US Dollars 1,000.
Therefore, the system is both cost-effective and useful for the outpatient clinic
or casualty setting, or on house calls for the purpose of patient education. In
the future, the authors plan to introduce the clinical application of a high
vision camera and an infrared camera as medical instruments for clinical and
research situations.
PMID- 17029162
TI - Current aspects of surgical management of GERD.
AB - Gastroesophageal reflux disease (GERD) is one of the most common pathologies
treated by primary care physicians. Despite advances in antacid pharmacological
treatments, many patients remain refractory to maximal medical therapy. In
addition, many others are either unable to tolerate the side effects of the drugs
or simply are unwilling to receive life-long daily medications. Laparoscopic
Nissen fundoplication has evolved as the surgical procedure of choice for
patients with GERD. Although the durability of surgical management has been
questioned, experienced surgeons achieve long-term reflux cure rates of about 85%
to 95%. Barrett's esophagus has recently been considered an additional indication
for surgical therapy of reflux due to evidence of dysplasia regression following
a 360 degrees fundoplication. However, the timing of surgical intervention and
the exact procedure for patients with both short- and long-segment Barrett's
esophagus remains debatable. Esophageal dysmotility in surgical patients with
GERD has traditionally been approached by "tailoring" the degree of
fundoplication. Recent evidence suggests that partial fundoplication may not be
effective and that full fundoplication should still be employed. The degree of
dysmotility prohibitive to a full 360 degrees fundoplication remains
controversial and should be addressed with future randomized trials. Finally,
patients with failed fundoplication represent a formidable diagnostic dilemma and
a technical challenge. In experienced hands, these patients can still benefit
from minimally-invasive restorative or "re-do" fundoplications with minimal
perioperative morbidity and good long-term results.
PMID- 17029163
TI - Initial clinical experience with telemetrically adjustable gastric banding.
AB - BACKGROUND: The feasibility and safety of laparoscopic adjustable gastric banding
for treatment of morbid obesity has been demonstrated in a large number of
studies. Access port-related complications constitute a significant part of all
complications related to gastric banding. Further, adjustment of hydraulic
gastric bands can be fairly lengthy, uncomfortable, and is not a precise
procedure. A study was performed to assess the usefulness and efficacy of a new
type of band adjusted telemetrically without the need for an access port. The
initial worldwide results of the first telemetrically adjustable gastric band for
morbid obesity (EASYBAND EndoArt Medical Technologies, Switzerland) in two German
academic centers are described herein. METHODS: EASYBAND is a purely mechanical
gastric band, in which adjustment is achieved by means of an embedded micromotor,
controlled by an external control unit using telemetry. The exact band diameter
is displayed continuously during adjustment on the external control unit screen.
Thirty-seven patients, means 36 +/- 8 (range: 22-60) years, 7 (19%) men and 30
(81%) women, with a mean body mass index (BMI) of 44.1 +/- 4.5 (range: 35.6
59.6), were implanted using the standard laparoscopic technique during the period
from June 2005 to October 2005. Prospective data were collected on all morbidly
obese patients who underwent laparoscopic telemetrically adjustable gastric
banding (LTAGB). RESULTS: No serious adverse events occurred during the operative
period or immediately postoperatively in relation to the device. A mean of 3.0 +/
0.6 adjustments per patients were performed during the follow-up schedule at
one, three and six months. The band diameter was set to 29 mm (fully open) at
implantation, 24.5 mm +/- 0.5 mm at one month, 23.3 mm +/- 0.7 mm at three
months, and 23.0 mm +/- 1.0 mm at six months. The mean percent excess weight loss
was 10.2% +/- 4.5% at one month, 23.8% +/- 8.8% at three months, and 30.2% +/-
10.5% at six months. CONCLUSION: This initial study shows that the new
telemetrically adjustable gastric banding device is implanted and operated
safely, allows for atruamatic band adjustments with superior patient comfort, and
leads to early excess weight loss comparable to that achieved by other gastric
bands. Longer-term follows and larger population studies are needed to establish
the final safety and performance profile of the telemetric gastric band.
PMID- 17029164
TI - Stapled hemorrhoidectomy.
AB - The procedure of stapled hemorrhoidectomy has been established as a safe and
effective method for treating symptomatic hemorrhoids not responsive to more
conservative measures. This chapter discusses the issues of safety, efficacy,
durability, and cost of this procedure. In addition, we outline techniques for
performing the procedure safely and effectively.
PMID- 17029165
TI - Thyroid surgery: new approach to dissection and hemostasis.
AB - The essential objectives for thyroidectomy are avoidance of injury to the
recurrent laryngeal nerves (RLNs), conservation of the parathyroid glands, an
accurate haemostasis, and an excellent cosmesis. In the last 10 years, major
improvements and new technologies have been proposed and applied in thyroid
surgery, among these mini-invasive thyroidectomy, regional anaesthesia, and
intraoperative neuromonitoring. Moreover, new devices for achieving dissection
and haemostasis have been proposed. The purpose of ligating vessels is to
maintain the surgical site free from an excess of blood and reduce blood loss in
patients. This chapter reviews relevant medical literature published in the
English language since 1990 on thyroid surgery techniques with well-controlled
trials on haemostasis and dissection. Searches were last updated October 2005.
PMID- 17029166
TI - Laparoscopic cholecystectomy: past, present, and future.
AB - Laparoscopic cholecystectomy is one of the most commonly undertaken procedures in
General Surgery with more than 500,000 performed annually. Overall, the
complication rate is less than 1.5%, and the mortality rate is less than 0.1%. As
such, laparoscopic cholecystectomy was considered by most to be at its zenith
since its inception in the early 1990 s. Advancements in technology and equipment
have opened new doors to physicians and allowed the laparoscopic cholecystectomy
to once again evolve. Traditional four-port cholecystectomy has given way to
three- and even two-port techniques. Standard 12-mm ports have been replaced by 2
mm ports, and experiments have now been implemented to achieve cholecystectomy
with no ports-known as the transgastric technique. The authors reviewed evolution
of these techniques that included a synopsis of our experience with the three
port cholecystectomy, as well as the future direction of laparoscopic surgery.
PMID- 17029167
TI - Laparoscopic low anterior resection for rectal cancer.
AB - More so than with other types of colon cancer, rectal cancer is associated with a
range of laparoscopic surgical techniques. Treatment of cancer of the lower
rectum requires favorable operative fields, minimal contact with the tumor during
dissection, and delicate surgical procedures to avoid nerve damage. Such surgery
thus requires immobilizing the trunk so the patient can be repositioned as
needed, placing ports at appropriate locations, as well as careful handling of
surgical equipment. To minimize the risk of disseminating cancer cells during the
procedure, the surgery should be restricted to patients with early-stage cancer.
The most difficult surgical procedure is resection of the lower rectum. While
safe resection of the intestinal tract was difficult using previously available
surgical equipment, newly developed equipment makes today's resections much safer
and easier. Indications for surgical intervention should be broadened carefully,
based on a deeper understanding of the surgical anatomy within the pelvis and on
various relevant oncological and technical factors.
PMID- 17029168
TI - Laparoscopic-assisted colectomy: technique and discussion.
AB - Minimally invasive surgery has undergone rapid development over the last 20 years
and has greatly impacted the field of General Surgery. Removal of the appendix
and gallbladder by way of laparoscopic means has become standard in surgical
training and care. More complex procedures also are becoming incorporated into
surgical resident education and routine clinical practice. Colon cancer
operations, previously performed by an open approach to ensure adequate resection
of the specimen and draining lymph nodes, are currently being performed
laparoscopically by experienced surgeons with equivalent recurrence, morbidity,
and overall mortality rates. In this chapter, the technique of laparoscopic
colectomy is described and advantages and disadvantages are discussed. The
literature is reviewed and this technique compared with the open procedure. The
authors contend that laparoscopic colectomy is a suitable, and perhaps
preferable, alternative to open procedures for benign or malignant colon disease,
with acceptable long-term results.
PMID- 17029169
TI - Bioactive prosthetic material for treatment of hernias.
AB - HYPOTHESIS: Laparoscopic herniorrhaphy using Surgisis (Cook Surgical,
Bloomington, IN, USA) mesh is an effective long-term treatment for repair of
inguinal hernia. PATIENTS AND INTERVENTION: Between August 1999 and April 2005,
67 patients underwent laparoscopic inguinal hernia repair by the total
extraperitoneal (TEP) mesh placement technique using Surgisis mesh. A total of 82
primary direct, indirect, pantaloon, and femoral hernias were repaired using this
technique. MAIN OUTCOME MEASURES: Postoperative complications and recurrence as
evaluated at two weeks, six weeks, three months, six months, one year, and yearly
thereafter for up to five years. RESULTS: The operations were performed
successfully on all the patients. One revision was done to an open procedure.
Postoperative complications were typical of inguinal hernia surgery. Average
follow up was 38 (range: 4-72, median: 35 months. Four non-technical recurrences
following repair of direct hernias were reported, which indicates a 4.9%
recurrence rate. No recurrences of indirect hernias were noted. CONCLUSIONS:
Laparoscopic inguinal herniorrhaphy using Surgisis mesh is effective in treatment
of primary inguinal hernias in adults with minimal complications and recurrence
up to five years of follow up.
PMID- 17029170
TI - Endoscopic extraperitoneal inguinal hernioplasty: disposable and reusable
instruments.
AB - Endoscopic totally extraperitoneal inguinal hernioplasty, TEP, has become an
established technique for repair of inguinal hernia. The performance of TEP
usually requires a number of disposable instruments. The high cost of these
devices has been a deterrent to development of laparoscopic surgery. Success in
cost containment is pivotal to enhance a wider application of TEP and benefit
more patients, particularly in public hospitals. The differences in the design
and material of disposable and reusable instruments account for distinction in
their handling and safety attributes. Replacement of disposable instruments by
reusable ones sometimes requires modification of surgical techniques. Reusable
instruments are economically advantageous, but they require sterilization. Wear
and tear of these reusable tools after multiple procedures sometimes causes
unexpected problems during operation. This chapter reviews the pros and cons of
reusable and disposable instruments for performance of TEP. The selection of
reusable or disposable instruments should balance the cost of the procedure,
convenience of the operation theatre, safety of the patient, and experience of
the surgeon. Instruments, whether reusable or disposable, should offer value for
money.
PMID- 17029171
TI - What is next in inguinal hernia surgery?
AB - Traditionally, the inguinal hernia repair is performed through an incision in the
groin. Different kinds of operations are suggested as best repairs by using the
patient's own tissue, or use of prosthetic mesh to reinforce the abdominal wall.
The advent of the laparoscopic repair that also uses prosthetic mesh, made it
even more complex to determine the best repair. Using the Evidence Based Medicine
(EBM) principles, endpoints of the treatment are not only based on recurrence
rates, but also on complications, patient satisfaction, convalescence, and costs.
Several meta-analyses concluded that use of mesh is superior to the non-mesh
operations. More difficult to determine is which mesh repair, open or
laparoscopically, is the best. The laparoscopic repair is difficult and less
suitable for general practice, but the open-mesh repair results in a higher
percentage of chronic postoperative pain. Further research should be focused on
making the laparoscopic repair less complicated, and development of new meshes
for open surgery that reduce the amount of persistent postoperative pain.
PMID- 17029172
TI - Laparoscopic myomectomy: a report of 982 procedures.
AB - We have reported the experience of two referral laparoscopic gynecologic centers
in Italy considering the results of almost 1000 laparoscopic myomectomies,
including complication rate and fertility outcome. From January 1991 to December
2003, a total of 982 single or multiple laparoscopic myomectomies (LM) were
performed. Indications were infertility, recent and significant uterine
enlargement, and other symptoms such as pelvic pain, menometrorrhagia, and
abnormal bleeding. All surgical procedures were performed by three surgeons in
two different endoscopic centers. Surgery outcome and information about
subsequent fertility and obstetric outcome were reported. Myomectomies were
performed using a standard technique with three ancillary suprapubic ports. In
cases of deep intramural myomas, we injected the myomas with vasoconstrictive
agents. A vertical incision of the serosa was made and mechanical enucleation of
the myomas was performed whenever possible. A suture in one or two layers with
large, curved needles (CT 1, 30 mm) swaged to polyglactin 1 or 0 sutures was
performed. Extraction of the removed myomas took place with electric
morcellation. Most patients (47%) had more than one myoma, with a maximum of
eight per patient (average myomas removed for patients: 2.23). Myoma size ranged
from 1 cm to 20 cm (average 67.20 mm +/- 27.1 mm). Most of the myomas (75%) were
intramural. The average drop in hemoglobin concentration was 1.06 g +/- 0.86
g/100 ml. The duration of the entire procedure ranged from 30 min to 360 min with
a mean of 104.5 min. The conversion rate to laparotomy was 1.29% and no major
intraoperative complications occurred. The mean postoperative hospital stay was
2.02 days +/- 0.61 days and we had three serious postoperative complications. The
overall rate of intrauterine pregnancy following LM was 62.53% and the abortion
rate was 15.9%. Data suggest that laparoscopic myomectomy is a safe and reliable
procedure, even in the presence of multiple or very enlarged myomas, with a low
complication rate and satisfying long-term results.
PMID- 17029173
TI - Adhesiolysis in severe and reccurent cases of adhesions related disorder (ARD) -
a novel approach utilizing lift (gasless) laparoscopy and SprayGel adhesion
barrier.
AB - We investigated the feasibility and outcome of adhesiolysis in patients with
severe and reccurent adhesions using lift (gasless) laparoscopy and a SprayGel
adhesion barrier at the Institute for Endoscopic Gynecology (EndoGyn). The design
included a prospective evaluation of lift (gasless) laparoscopic adhesiolysis in
combination with a SprayGel adhesion barrier. A new score for bowel adhesions was
developed and applied. All 35 patients with severe and reccurent adhesions
underwent a lift-laparoscopic adhesiolysis with the Abdo-Lift and SprayGel
adhesion barrier, a second-look laparoscopy at Day 7 and, in case of continuation
of pain, a third-look laparoscopy within 6 months after the initial surgery. All
patients were operated upon without conversion to laparotomy. The reduction in
the adhesion score of adhesions at the second-look laparoscopy was overall (sum)
89.8% (90.1% reduction in extent, 89.3% reduction in severity, and 89.9%
reduction in grade). Five patients (14.3%) had a third-look laparoscopy within 6
months after the initial surgery, in which four cases of adhesion reformation
were confirmed. However, the scores were reduced compared to the initial surgery,
especially in grade (94.2%) and severity (93.2%). In these analyses, SprayGel was
uniquely effective in improving the success rates of adhesiolysis when combined
with lift (gasless) laparoscopy and good hemostasis techniques. Adhesiolysis with
Abdo-Lift and SprayGel had unparalleled efficacy in the adhesiolysis procedure
even in those patients in whom other solutions have not worked. An overall
reduction of adhesions by 89.9% at second-look laparoscopy was found. Even if
five patients (14.3%) required a third-look laparoscopy where four cases of
adhesion reformation were confirmed, the scores were reduced when compared to the
initial surgery, especially in grade and severity.
PMID- 17029174
TI - Laparoscopic Myomectomy.
AB - Laparoscopic myomectomy (LM) is an increasingly accepted method of treatment for
symptomatic uterine leiomyomas. It affords patients a minimally invasive surgery
compared to the more traditional abdominal approach. Studies have shown the
benefits of decreased blood loss, shorter hospital stay and recovery period, as
well as decreased postoperative pain and fever in comparison to abdominal
myomectomy (AM). Even myomas larger than 5 cm can be laparoscopically resected
safely in the hands of an experienced surgeon. To date, studies indicate a
decreased adhesion rate with the laparoscopic approach compared to the abdominal
procedure. The use of adhesion barriers may decrease this rate further. In
infertile women with myomas, pregnancy and live-birth rates improve following LM,
and appear to be comparable with those rates achieved following AM. The data
regarding the risk of uterine rupture in pregnancy following LM is limited.
However, small studies show safe outcomes when patients are managed with the same
degree of caution one might employ with post-abdominal myomectomy patients. In
performing LM, a precise and diligent technique should be exercised to ensure a
secure, multilayer closure.
PMID- 17029175
TI - Advanced technologies for cardiac valvular replacement, transcatheter innovations
and reconstructive surgery.
AB - Since the 2002 Surgical Technology International monograph on valvular
prostheses, there have been significant developmental and investigative advances.
Aortic bioprostheses and mechanical prostheses have undergone design changes to
optimize hemodynamics and prevent patient-prosthesis mismatch to have a potential
satisfactory influence on survival. There has been continual technological
improvements striving to bring forward advances that improve the durability of
bioprostheses and reduce the thrombogenicity of mechanical prostheses. There also
has been a continuance to preserve biological tissue with glutaraldehyde, rather
than clinically evaluate other cross-linking technologies, by controlling or
retarding calcification with therapies to control phospholipids and residual
aldehydes. The techniques of mitral valve reconstruction have now been well
established and new annuloplasty rings have been designed for the potential of
maintaining the anatomical and physiological characteristics of the mitral
annulus. Several objectives exist for annuloplasty, namely remodeling of the
length and shape of the dilated annulus, prevention of dilatation of the annulus,
and support for the potentially fragile area after partial-leaflet resection.
Currently, there exists an emergence of catheter-based therapies for management
of aortic stenosis and mitral regurgitation. For management of selected
populations with critical aortic stenosis, techniques for aortic valve
substitution have been developed for both antegrade and retrograde catheter
techniques, as well as apical transventricular implantation. Mitral regurgitation
has been addressed by experimental transcoronary sinus, stent-like devices and
transventricular, edge-to-edge leaflet devices. The devices, descriptions and
pictorial images comprise this monograph.
PMID- 17029176
TI - Mitral valve: toward complete repairability.
AB - During the last 50 years, there has been an exponential increase in our
understanding of the structure and function of the mitral valve in health and
disease. Large numbers of patients have undergone mitral-valve reparative
procedures worldwide with variable results. In our initial 10-year experience in
which traditional techniques were used for repair of mitral regurgitation, a 70%
success rate was achieved. In 1995, a critical reappraisal of the common causes
of failure to repair, or failure of repair and developed improved surgical
approaches for these patients began. The conditions addressed were massive
bileaflet prolapse ("Barlow's valves"); anterior leaflet prolapse; multisegment
chordal failure; commissural accessory leaflet tissue prolapse; and leaflet
destruction by endocarditis. A widely applicable standard technique was developed
that the author and colleagues called the "American Correction." It emphasizes
chordal replacement with polytetrafluoroethylene (PTFE) artificial chordae,
importance of the line of apposition of the leaflets, and importance of
simultaneous dynamic adjustment of the chordal length and anteroposterior
dimension of the mitral annulus. In addition, use of multiple techniques in 30%
of patients to complete the repair has been emphasized. These techniques resulted
in a 90% repairability rate for all pathologies and 100% for myxomatous-mitral
insufficiency. These techniques also have led to a decline in reoperation rates,
and improved long-term durability. Continued evaluation with intraoperative and
postoperative three-dimensional (3-D) echo provides further insights and
refinement of mitral-repair techniques.
PMID- 17029177
TI - Early mobilization after aortic valve surgery.
AB - In recent years, the focus in peri-operative care of cardiac patients has shifted
from trying to create a stress-free environment to hasten the recovery of
patients by providing early extubation, early mobilization, and enteral
nutrition. Fast-track cardiac surgery has therefore made a paradigm shift in
postoperative care. However, evidence on the safety of early postoperative
mobilization in high-risk groups like aortic valve replacement surgery is
lacking. Physiological evidence from controlled studies in patients undergoing
aortic valve replacement (AVR) showed that heart rate increases and stroke volume
falls with maintenance of cardiac output. However, the increase of 50% to 60% of
oxygen consumption during mobilization is covered by increased oxygen extraction,
resulting in marked mixed venous oxygen desaturation. These physiological changes
during postoperative mobilization were also seen in CABG patients. The
mobilization pattern was also maintained on the second day after surgery. No
serious side effects were observed in the controlled trials of mobilization of
AVR patients after cardiac surgery. Over a 13-year period, we have mobilized more
than 1200 AVR patients. No serious situations have occurred during or in direct
connection to mobilization.
PMID- 17029178
TI - Isthmus endoprosthesis stent-graft treatment: implantation of relay dedicated
device.
AB - Among the 123 patients treated in our department by endovascular stent graft, 113
(91.8%) were identified as having involvement of the isthmus. Therefore, the
incorrectly defined descending aortic disease is essentially a pathology of the
isthmus that represents the distal portion of the arch. The key to the treatment
of all types of aortic lesions rests on understanding the morphology of this
region gifted with a "double S" configuration. Current thoracic devices are
noncompliant systems and should be modified greatly, taking into account that the
media of the aorta has a semi-compliant behavior. The resultant of power
transmission is oriented at 45 degrees and produces a transmural radial force
that animal implantation has demonstrated to be a torsional movement. The
improvements in new devices actually result in a new generation of endoprostheses
that seem to be closely related to the anatomy of the patient by increasing the
conformability and, therefore, we expect an increase in durability. To test these
features, we have studied a new stent graft in different settings of thoracic
aortic disease. The new device should conform to current standards while
simultaneously transmitting torsional forces. The dedicated delivery system
should be arch-compatible, flexible but sufficiently rigid, and able to be three
dimensionally oriented. Moreover, the new stent graft should follow the three
dimensional anatomy of the "double S" configuration of the isthmus area and thus
reduce the mismatch between the aorta and the device itself.
PMID- 17029179
TI - Use of modular large femoral heads without liners in hip arthroplasty.
AB - The use of large-diameter femoral heads in total hip arthroplasty appears to
reduce the risk for dislocation, and potentially improve articular wear.
Moreover, large-diameter total hip femoral heads have been determined to increase
range of motion. The purpose of this study was to report our experiences with
this new device. In our patient cohort, many patients have done extremely well in
the short-term with this new device, and it seems these patients function better
than those with a standard total hip arthroplasty. The patients who experience
less pain are able to return to full activities postoperatively. The preliminary
results of this study are encouraging, and large femoral head prosthesis appears
to be a great choice for orthopaedic surgeons in primary total hip arthroplasty.
PMID- 17029180
TI - Manipulation with prolonged epidural analgesia for treatment of TKA complicated
by arthrofibrosis.
AB - Inability to achieve adequate range of motion (ROM) after total knee arthroplasty
(TKA) represents a frustrating complication for both patient and surgeon.
Manipulation under anesthesia is indicated in TKA having less than 90 degrees ROM
after six weeks, with no progression or regression in ROM. A modified technique
has evolved for patients with chronic regional pain syndrome (CRPS) symptoms or
persistent stiffness after standard manipulation. A retrospective review was
conducted to determine the efficacy of the modified technique, which uses
epidural anesthesia continued for postoperative analgesia, hospital stay of one
to three days, continuous passive motion (CPM) for two to three days, and daily
physical therapy (PT). Between 1997 and 2003, 5714 TKAs were performed in 4106
patients. Manipulation using a standard technique was performed on 334 (5.8%)
knees in 273 patients. Manipulation using a modified technique was performed on
65 (1%) knees in 60 patients. Age averaged 58 years and body mass index (BMI)
averaged 34.39. Follow up averaged 18.4 months. ROM improved significantly from
71 degrees to 102 degrees (p < 0.0001). Knee Society pain, function, and total
clinical scores all improved significantly (all p < 0.0001). Successful results
were observed in 48 (74%) knees. Four (6%) additional knees achieved a successful
result after a subsequent manipulation. Nine (14%) knees required component
revision for treatment of persistent arthrofibrosis, which included one full
revision, five polyethylene exchanges, and three revisions of femoral component
and polyethylene. Two significant complications occurred: one subdural hematoma
and one death due to pulmonary embolism. Although not without complications,
manipulation under epidural anesthesia represents a viable option for treatment
of persistent stiffness after TKA; 80% of these difficult cases achieved
successful results.
PMID- 17029181
TI - Pulsed electrical stimulation in patients with osteoarthritis of the knee: follow
up in 288 patients who had failed non-operative therapy.
AB - BACKGROUND: Optimized pulsed electrical stimulation (PES) regulates chondrocyte
genes, enhances production of cartilage matrix materials, and inhibits production
of matrix catabolic factors. METHODS: This prospective, cohort study examined the
use of a PES device in treatment of knee osteoarthritis (OA) in patients who had
failed non-operative therapy. Primary outcome measures were patient and physician
global evaluation, and patient assessment of knee pain. RESULTS: This study
included 288 (95 men, 193 women) patients who used the device from 16 to more
than 600 days (mean: 889 hours). Improvement in all efficacy variables (p <
0.001) occurred. A dose-response relationship between effect size and hours of
usage was observed as cumulative time increased to more than 750 hours.
Improvement in patient or physician global occurred in 59.0% of patients who used
it less than 750 hours, and for 73.0% of those who used it more than 750 hours.
An economic analysis of a sub-group of patients showed that 45.3% reduced
nonsteroidal anti-inflammatory drug (NSAID) use by 50.0% or more. CONCLUSIONS: A
highly optimized PES device successfully attenuated knee OA symptoms in patients
who had failed non-surgical therapy. Less than 250 hours of therapy provided
relief, but improvement increased in a dose-response manner after 750 hours of
cumulative use.
PMID- 17029182
TI - Endoscopic assisted lumbar microdecompressive spinal surgery with a new SMART
endoscopic spine system.
AB - In response to the rapid development and demand of outpatient endoscopic
minimally invasive lumbar surgical technique, the SMART endoscopic spine system
was developed for neurodecompression. This lumbar spine surgery is performed with
a small skin incision, dilatation surgical technology, and an endoscopic-assisted
spinal surgical system with progressive serial tubular retractors providing
superior lighting and better visualization of the operative field for performing
minimally invasive spinal surgery (MISS). The SMART system incorporates the
advantages of posterior paramedian endoscopic assisted microdecompressive
surgical spinal system and posterolateral endoscopic lumbar system. This
versatile SMART endoscopic spine system with various sized working channels
provides a generous and optimal access for endoscopic MISS of microdecompression
of herniated lumbar disc, degenerative spinal disease, spinal stenosis, and
removal of intraspinal lesions as well as creating an access for spinal
arthroplasty and spinal fixation. With the unique features of the SMART system,
the surgeon can take advantage of microscopic, endoscopic, or direct vision for
microdecompressive spinal surgery, bridging endoscopic and conventional spinal
surgery. It appears easy, safe, and efficacious. This less traumatic and easier
outpatient MISS treatment leads to excellent result speedier recovery, and
significant economic savings. The SMART endoscopic spine system, surgical
indications, operative techniques, and the potential complications and their
avoidance are described and discussed herein.
PMID- 17029183
TI - In-vivo endoscopic visualization of patho-anatomy in painful degenerative
conditions of the lumbar spine.
AB - The degenerative processes in an aging spine have been defined traditionally only
by our knowledge of the biology of disc and facet degeneration, as well as
interpretation of post-mortem cryosections by forensic anatomist Wolfgang
Rauschning, M.D. In this chapter, visualization of in-vivo patho-anatomy in a
degenerating disc and spinal segment is demonstrated at surgery using the Yeung
Endoscopic Spine System (Y.E.S.S.), (Richard Wolf Surgical Instrument Company,
Vernon Hills, IL, USA). An Institutional Review Board (IRB)-approved study of
endoscopic treatment for degenerative conditions of the lumbar spine incorporated
intraoperative probing under local anesthesia and endoscopic treatment of the
visualized patho-anatomy. An intraoperative evocative chromo-discogram, using
indigocarmine, was used to elicit discogenic pain and label the fissured and
degenerative nucleus pulposus for surgical removal and thermal modulation.
Painful patho-anatomy was probed in a conscious patient. The most common
endoscopic finding was Inflammatory tissue in the disc and annulus. Inflammation
was correlated with the presence of annular tears. Patho-physiologic changes that
affect the exiting nerve, which contains the Dorsal Root Ganglion (DRG), was
associated with stenotic and chemical irritation. Unavoidable postoperative
dysesthesia was associated with the presence of an inflammatory membrane, and
removal or thermal coagulation of "anomalous" furcal nerves in the foramen that
branched off of the exiting spinal nerve. Neo-angiogenesis and neurogenesis in
the inflammatory membrane present in the foraminal triangle was a new finding not
reported in traditional clinical studies. Visualization and treatment of
pathologic findings inside (annular tears) and outside the disc in Herniated
Nucleus Pulposus (HNP), synovial cysts, foraminal stenosis, central stenosis,
spondylolisthesis, is demonstrated. The endoscopic foraminal approach to the
spine and disc is a technique that provides access to patho-anatomy in the lumbar
spine not usually feasible with traditional surgical methods. Favorable surgical
results allow for continued evolution of the endoscopic method, concomitant with
the continued evolution of endoscopic spinal surgery.
PMID- 17029184
TI - Posterolateral spinal cord decompression in patients with metastasis: an
endoscopic assisted approach.
AB - Spinal tumors that are radioresistant or cause bony compression of the spinal
cord often require surgical decompression to protect or restore neurological
function. Metastatic lesions and primary tumors such as multiple myeloma usually
arise in the vertebral body, which can collapse and become unstable, and can
compress the anterior columns of the cord. Laminectomy is often ineffective in
these patients, and direct anterior decompression through thoracotomy is the
widely-accepted solution to the neurological problem. The anterior surgical
approach is particularly challenging in the upper thoracic spine. Patients with
limited pulmonary reserve due to pneumonectomy or pulmonary metastasis might not
tolerate the loss of lung capacity necessitated by either thoracotomy or
thoracoscopy. Because posterior instrumentation is usually needed to provide
stability following corpectomy and spinal cord decompression, posterolateral
approaches to spinal cord decompression have gained favor in recent years.
Posterolateral decompression offers advantages over the combined anterior and
posterior approach, reducing operative time, morbidity, and hospital stay.
Drawbacks to traditional posterolateral decompressions include poor visualization
of the tumor immediately anterior to the spinal cord and the need to manipulate
the spinal cord to completely remove a tumor adherent to the dura. Endoscopically
assisted posterolateral decompression allows decompression of the anterior
surface of the spinal cord, the point of pressure in most circumstances.
Endoscopic video assistance facilitates vertebrectomy, cord decompression, and
anterior reconstruction, all performed through the same posterior incision.
Endoscopic assisted spinal cord decompression dramatically reduces morbidity, ICU
requirements, and inpatient hospitalization and has proven useful for a variety
of metastatic tumors at every level of the spinal column.
PMID- 17029185
TI - Interspinous process decompression (IPD) system (X-STOP) for the treatment of
lumbar spinal stenosis.
AB - With increased life expectancy and an aging population, many patients suffering
from progressive lumbar spinal stenosis with symptomatic neurogenic intermittent
claudication (NIC) have been limited to a choice between nonsurgical therapies or
a more traumatic decompressive surgical procedure, with or without lumbar fusion.
The interspinous process decompression (IPD) system, the X-STOP implant, was
developed to provide a minimally invasive alternative therapeutic treatment of
lumbar spinal stenosis. The X-STOP IPD system, surgical indications, operative
techniques, and the potential complications and their avoidance are described and
discussed herein.
PMID- 17029186
TI - Intradural lysis and peripheral nerve implantation for traumatic obsolete
incomplete paralysis.
AB - Twenty-eight patients who suffered traumatic obsolete incomplete paralysis were
treated with intradural lysis and peripheral nerve implantation by a microsurgery
technique. The endorachis was opened and the fibrous bands adhering to the spinal
cord from the arachnoid, pia mater spinalis, ligamenta denticulatum, and the
initial part of the nerve root were completely relieved. The abnormal spinal cord
was then opened by three to six incisions, which were each 0.1 mm to 0.2 mm deep
and longer than the abnormal portion. A cyst found in the back or side of the
spinal cord was opened and the liquid in it was drained. After that, the denuded
spineurium and perineurium of the autogenous sural nerve were grafted, which
makes the character and aspect of the nerve like the cauda equine. The nerve was
longitudinally implanted into the incised spinal cord, and the cyst was waded
with grafted nerve and at least one of them is ectropion sutured with the pia
mater with 9-0 scatheless wire as a drain. Finally, the endorachis was covered by
sacrospinal muscle flap. These patients were followed for 2 years to 8 years
(average 3.5 years), and the sensibility and motion of each increased at least
one grade. The strength of the main muscle was increased two grades and reached
four grades in 11 patients, and the capability to walk was recovered. Relieving
of the adhesion in the endorhachis, carving the cicatricial spinal cord, and
implanting the autogenous peripheral nerve yields good results by initial
clinical observation for traumatic obsolete and incomplete paralysis.
PMID- 17029187
TI - Treatment of osteochondral lesions of the talus with cryopreserved talar
allograft and ankle distraction with external fixation.
AB - This article presents the results of a retrospective review of six osteochondral
lesions on six patients (five men and one woman) treated with transplantation of
cryopreserved talar allograft and ankle joint distraction. All patients
complained of ankle pain existing for a long time secondary to a traumatic
episode confirmed through MRI. Lesions ranged in measurement from 0.8 cm x 0.8 cm
to 3.2 cm x 1.8 cm with an average size of 2.1 cm x 1.5 cm. Each patient
underwent talar dome transplantation using fresh frozen talar allograft followed
by ankle distraction. Distraction was obtained using a three-ring multiplanar
external fixation device. All surgeries were performed between 2002 and 2004. All
external fixators were removed at 8 weeks and patients remained partial-weight
bearing in a removable cast boot for an additional 8 weeks. Serial postoperative
radiographs showed complete consolidation of the allograft within 16 weeks. The
average follow up time was 24 months, and all patients related a subjective
decrease in symptoms and increase in activity levels. Patients were also
evaluated utilizing the Maryland Foot Score both pre- and postoperatively.
Preoperatively, four patients were graded as fair and two were graded as poor.
Postoperatively, two patients related excellent results, three patients related
good results, and one patient related fair results. Several patients experienced
minor complications such as pin site irritation (five patients), painful talar
wire (one patient), and periostitis (one patient). No patients experienced any
major complications and none have required additional surgery. We feel that these
initial results warrant further investigation of this treatment.
PMID- 17029188
TI - Alloplastic reconstruction of the temporomandibular joint in treatment of
craniofacial developmental or congenital anomalies: a surgical case report.
AB - OBJECTIVE: To describe the surgical planning and treatment approach in addressing
the oral and maxillofacial needs for one particular patient suffering congenital
anomalies of the craniofacial anatomy. A secondary objective is to restore
mandibular and maxillary function and esthetics to the young, adult patient. The
tertiary objective is to educate the surgeon as to alloplastic implant options
that may be available to restore function and relieve pain for the patient
missing certain anatomical structures from birth. METHODS: Through the use of
advanced medical imaging tools, a thorough understanding of the patient's prior
failed medical treatments, and a meticulous understanding of the benefits of
alloplastic reconstruction, the surgeon can mitigate patient symptoms and at the
same time increase the probability of a successful outcome. The surgeon can then
collaborate with the surgical and implant design team to not only prescribe the
surgical correction necessary, but also design and construct the actual
temporomandibular joint (TMJ) and mandibular implants used for the case, as well
as perform mock surgery on a stereolithography anatomical (SLA) model needed to
restore function and esthetics for the patient. The end result is that a Patient
Specific (custom) (TMJ Implants, Inc., Golden, CO, USA) prosthesis can then be
manufactured and adapted surgically to the patient's unique anatomy. RESULTS: The
early results from this alloplastic reconstructive surgery have brought forth the
anticipated results of replacement of the congenitally absent TMJ, improvement of
jaw function, reduction of joint pain, as well as improvement of the esthetics.
Without this breakthrough surgical development, many of these congenital
anatomically deficient patients would not be able to enjoy normal breathing,
mastication, jaw function, esthetics, oral and dental health, and the emotional
relief that these corrections allow. CONCLUSIONS: Many patients who suffer birth
related anatomical deficiencies (such as cleft lip and branchial arch syndrome)
never receive the surgical correction necessary. Many have had autogenous
reconstruction of missing mandibular and TMJ structures only to relapse, at
times, into a more disfiguring and lasting condition. By simply placing a
Christensen Fossa-Eminence Prosthesis (FEP) and Condylar Prosthesis (CP) in a
total joint-replacement solution, one is more likely to achieve satisfactory TMJ
mobility and reduction in pain, as well as the mechanical replacement of missing
anatomical structures and predictable and lasting improvement. As an additional
benefit, the patient also would enjoy enhanced esthetics.
PMID- 17029189
TI - Principles of microneurosurgery for safe and fast surgery.
AB - Since their introduction by Prof. Yasargil in the 1960s, Microneurosurgical
techniques have been the essentials of neurosurgical practice. Principles of
Microneurosurgery are mainly based upon handling the lesions of different
characteristics that can be localized in any part of the nervous system. Whereas
the aim is to treat these lesions with efficacy and precision, the performance
should be non-traumatic and minimally invasive. Delicate movements of instruments
under the magnification of an operating microscope require a good knowledge of
Microneurosurgical anatomy and experience. Professional teamwork is the essential
part of Microneurosurgical operations. Fascinating approaches are not practical
unless combined with appropriate positioning and optimal conduction of
Neuroanesthesia. Although the neurosurgical operations are highly dependent on
technological advancements, their use should be adjusted according to personal
preferences and financial resources. To keep the operations simple and fast, and
appreciate normal anatomy, only a limited array of instruments is preferable for
use. The basic principles of Microneurosurgery discussed in this chapter are
based on the Helsinki and Kuopio Neurosurgery practices in Finland, as well as
the Senior Author's (J.H.) experience in approximately 10,000 microsurgery
operations. The question to be addressed is: How does one perform operations
safer and faster while preserving the normal anatomy?
PMID- 17029190
TI - Local infusion therapy in the monkey brainstem: technical considerations.
AB - This chapter assesses the safety of freehand placement of an infusion catheter
(outer diameter, 0.3 mm) in brainstems of cynomolgus monkeys (Macaca
fascicularis) for local infusion therapy. A posterior midline approach through
the cerebellum and roof of the fourth ventricle was used to implant catheters
into a pontine target area. Computer tomography (CT), magnetic resonance imaging
(MRI), and histology were used to examine the position of the implants. The
freehand placement of a catheter resulted in approximately 5-mm variations in
anterior-posterior and dorsal-ventral locations of the targeted implantation
site. No evidence of morbidity from the surgery, or from the infusion process was
present. In conclusion, small-diameter catheters for chronic drug infusions can
be implanted safely into the brainstem, an eloquent region that has been
considered surgically inoperable. Infusion systems may offer a minimally
invasive, generally applicable tool to provide chronic therapy for central
nervous system (CNS) lesions.
PMID- 17029191
TI - The G401D mutation of OPA1 causes autosomal dominant optic atrophy and hearing
loss in a Chinese family.
AB - OBJECTIVE: To describe the clinical and genetic characteristics of a Chinese
family affected with optic atrophy 1 (OPA1). METHODS: Linkage analysis and DNA
sequencing as well as PCR/restriction fragment length polymorphism (RFLP)
analysis were performed to identify the disease-causing mutation. RESULTS: A
missense mutation, G401D in the OPA1 gene was identified, and the patients
demonstrate inherited syndrome of optic atrophy and hearing loss. CONCLUSION: The
present study demonstrates that a mutation in the OPA1 gene can cause optic
atrophy in Chinese patients, and supports the notion that OPA1 mutation may lead
to OPA1 combined with hearing loss.
PMID- 17029192
TI - [Study on the molecular background of Del phenotype in Chinese population].
AB - OBJECTIVE: To elucidate the molecular background of Del phenotype in the Chinese
population and explore new Del alleles. METHODS: Five hundred and fifteen RhD
negative blood samples was tested by Rh typing test, indirect antiglobulin test
and adsorption and elution assay to screen the Del phenotype. DNA of all the Del
samples was analysed by multiplex polymerase chain reaction (MPX PCR) for the
presence of RHD and by sequence-specific primer polymerase chain reaction (PCR
SSP) for Del alleles: RHD 1227A and RHD 885T. Samples which showed the negative
result by PCR-SSP, were additionally analysed by genomic DNA sequencing and cDNA
sequencing. RESULTS: Seventy-nine Del samples were found by adsorption and
elution assay. All these samples had RHD exons 3, 4, 5, 6, 7 and 9. Except 4 Del
samples, other 75 Del samples carried the RHD 1227A allele. None of the samples
had the RHD 885T allele. Four novel RHD alleles were found in these four Del
sample. There were RHD 3G-->A (GenBank DQ310735), RHD 28C-->T, RHD 53T-->C
(GenBank DQ451877,DQ451878), RHD 251T-->C (GenBank DQ310734). CONCLUSION: fnRh
blood group system is very complex. New D variation phenotypes and new RHD
alleles may be discovered ceaselessly.
PMID- 17029193
TI - [Functional interaction of the C-terminal of Nogo protein with connexin 26 and
the expression of Nogo's mRNA in the murine inner ear].
AB - OBJECTIVE: To screen and identify the proteins that interact with connexin 26
(CX26) and to analyze the expressions of these proteins in cochlea so as to
explore the proteins that relate to the trafficking, assembly, localizing and gap
junction functions of CX26. METHODS: The whole coding region of GJB2 (CX26) gene
was amplified from normal human genomic DNA by polymerase chain reaction (PCR)
and then directionally subcloned into the vector pGBKT7 plasmid of the Match
Maker Ga14 Two-Hybrid System 3 as a target to screen the interactive proteins of
CX26 from the human fetal brain cDNA library by the yeast two hybrid technique.
The false positive clones were discarded from the preys by repeated yeast two
hybrid method between CX26 and everyone of the preys respectively. The DNAs of
the insert of the identified positive clone were sequenced and BLAST analyzed
against the GenBank. Lastly, the mRNA of the gene encoding the identified protein
was analyzed in the murine inner ear by reverse transcription-polymerase chain
reaction (RT-PCR). RESULTS: The insert of one positive clone contained 867 bp
with the former 525 bp being coding region. The DNA sequence and the open reading
frame of the insert were identical to the 525 bp before the stop codes (including
the stop codes) and the 238 bp after the stop codes of RTN4 gene which encoded
Nogo protein. And the 174 amino acid residues encoded by the insert were those of
the C-terminal of Nogo protein: Nogo-A, Nogo-B and Nogo-C. RTN4 mRNA expressed in
the murine inner ear was confirmed by RT-PCR method. CONCLUSION: The C-terminal
of Nogo protein interacts with CX26. Nogo protein expresses in the inner ear and
may take part in the trafficking of CX26 or CX26 gap junction function.
PMID- 17029194
TI - [Characteristics of IGF-II gene imprinting in twin placentas].
AB - OBJECTIVE: To compare insulin-like growth factor II (IGF-II) gene imprinting in
twin placentas with singleton ones and to determine whether imprinting was
influenced by assisted reproductive technology, zygosity and fetal sex. METHODS:
One hundred and sixty cases of twin placentas and 42 cases of singleton ones were
recruited. Allele-specific IGF-II expression was determined by reverse
transcription-PCR combined with analysis of an Apa I-sensitive restriction
fragment length polymorphism. RESULTS: Although the incidence of IGF-II
imprinting loss was higher in normal twin placentas than in singleton ones (20.6%
vs 8.7%), there was no statistical significance. There were no significant
differences between twins conceived by assisted reproductive technology and those
conceived spontaneously (17.9% vs 24.4%), and between dizygotic and monozygotic
twins (22.4% vs 16.7%). The incidence of IGF-II imprinting loss in placenta of
female twins was statistically higher than that of male ones (26.4% vs 9.8%).
CONCLUSION: The risk of IGF-II gene imprinting loss is higher in female twins and
has no relationship with assisted reproductive technology and zygosity.
PMID- 17029195
TI - [A mutation in TGF beta1 gene encoding the latency-associated peptide in a
Chinese patient with Camurati-Engelmann disease].
AB - OBJECTIVE: To identify the mutation in transforming growth factor-beta1 gene (TGF
beta1) in a Chinese patient with Camurati-Engelmann disease(CED). METHODS:
Denaturing high-performance liquid chromatography (DHPLC) analysis was performed
on the whole seven coding exons and exon-intron boundaries, then the mutation was
identified by direct sequencing. RESULTS: Mutation screening of TGF beta1 in this
patient revealed a heterozygous missense mutation R218H in exon 4. CONCLUSION:
The identification of the mutation could provide essential data for subsequent
therapy and genetic counseling.
PMID- 17029196
TI - [Analysis of differential expression genes related to different metastasis
potential of adenoid cystic carcinoma using restriction fragments differential
display PCR].
AB - OBJECTIVE: To construct differential expression profiles of adenoid cystic
carcinoma cell lines for screening candidate genes related to metastasis and to
verify some candidate genes in adenoid cystic carcinoma. METHODS: Restriction
fragments differential display PCR (RFDD-PCR) was used to set up gene expression
profiles of adenoid cystic carcinoma cell lines-ACC-M and ACC-2, with high and
low metastasis potential respectively. Candidate genes were screened through
bioinformatics analysis. Then, a gene family of these candidate genes was checked
using semi-quantitative reverse transcription-PCR(RT-PCR). RESULTS: Two gene
expression profiles including 5420 gene fragments were constructed, 12 genes of a
family called matrix metalloproteinase genes (MMPs) were observed obvious
differentially expressed between two cell lines. Results of semi-quantitative RT
PCR also identified this different expression of MMP2,MMP7,MMP9,MMP14,MMP15 and
MMP24. CONCLUSION: The construction of gene expression profiles of ACC-M and ACC
2 cell lines makes the foundation for seeking the target genes of adenoid cystic
carcinoma. MMP2,MMP7,MMP9 and MMP15 may be relevant with carcinogenesis,
development and metastasis of adenoid cystic carcinoma, and different metastasis
potential may result from different subtype of MMPs gene family.
PMID- 17029197
TI - [Genetic heterogeneity for familial recurrent hydatidiform mole].
AB - OBJECTIVE: To determine the parental origin of the genome in the molar
pregnancies of two familes with familial recurrent hydatidiform mole (FRHM) and
to investigate whether the gene responsible for FRHM is likely to be located
within the 19q13.4 region in these familes. METHODS: The features of complete
hydatidiform mole (CHM) were confirmed by pathological examination. DNA of CHM
was prepared from sections of formalin-fixed paraffin-embedded blocks of molar
tissue following laser capture microdissection. The polymerace chain reaction was
used to amplify microsatellite polymorphisms in DNA from the patients, their
husbands and the captured molar tissue. Parental contributions to the molar
tissue were determined using ABI 310 GeneScan software. Genotyping and haplotype
analysis of the candidate region on 19q13.4 was performed for members of both
families using 25 microsatellite markers. RESULTS: One CHM from each family was
identified as a biparental complete hydatidiform mole. All patients were
heterozygous for most of the markers in the chromosome region of interest. In
addition the two affected sisters in one of the families had different genotypes
for the 19q13.4 region, suggesting that mutations in a different locus might be
responsible for the disorder in this family. CONCLUSION: The location of the gene
responsible for FRHM is unlikely to be located in the 19q13.4 chromosomal region
in these two families suggesting that FRHM shows genetic heterogeneity.
PMID- 17029198
TI - [Identification of two novel mutations of human blood coagulation factor V gene
in a Chinese family with congenital factor V deficiency].
AB - OBJECTIVE: To discover the mutations of human blood coagulation factor V (FV)
gene in a Chinese family with congenital factor V deficiency, and to explore the
molecular mechanism associated with the congenital factor V deficiency. METHODS:
PCR and DNA sequencing were used to look for the FV gene mutations in the
proband. And the novel mutation were testified by PCR restriction fragment length
polymorphism technique or reverse DNA sequencing. One hundred healthy volunteers
were chosen as controls at random. RESULTS: Two novel mutations were discovered
in the FV gene of proband, which were the A1763C missense mutation in exon 11 and
the splicing site mutation in the 3' terminal of intron 16 (G-->T). The pedigree
analysis showed that the two mutations inherited from his parents respectively:
the A1763C came from his father, and the G-->T from his mother. The A1763C
missense mutation in exon 11 was not found in each of 100 healthy volunteers.
CONCLUSION: The congenital deficiency of FV in the proband might be caused by the
A1763C missense mutation in exon 11 and the splicing site mutation in the 3'
terminal of intron 16, which jointly caused the proband to be a double
heterozygote.
PMID- 17029199
TI - [Associations between Ser447Ter gene polymorphism of lipoprotein lipase and
atherosclerotic cerebral infarction].
AB - OBJECTIVE: To investigate the relationship between lipoprotein lipase (LPL) gene
Ser447Ter polymorphism and atherosclerotic cerebral infarction (CI), and to
investigate the effect of Ser447Ter polymorphism on plasma lipids, carotid intima
media thickness (IMT) and carotid artery plaque (CAP) in patients with CI.
METHODS: PCR-restriction fragment lengh polymorphism (PCR-RFLP) technique was
used to detect LPL gene Ser447Ter polymorphism in 166 patients with CI (CI group)
and 72 healthy subjects (control group). Carotid IMT and CAP were measured with
carotid color ultrasonographic doppler for the patients and the controls.
RESULTS: CG+GG carriers had lower plasma triglyceride (TG) levels and higher high
density lipoprotein cholesterol (HDL-C) levels than CC carriers in CI group
(P=0.001 and P=0.007 respectively). CG+GG carriers had lower plasma TG levels
than CC carriers in control group (P=0.041). The frequency of G allele in CI
patients was significantly lower than that in control subjects (P= 0.014). There
was no statistical correlation between LPL Ser447Ter gene polymorphism and
carotid IMT and CAP. CONCLUSION: The Ser447Terls polymorphism of LPL gene is
significantly associated with plasma lipids and CI. G allele genotype may lead to
decrease of plasma TG and increase of plasma HDL-C. G allele may be a protective
genotype of CI.
PMID- 17029200
TI - [Comparative study of APOB gene 3'VNTR polymorphisms between natural longevity
and controls in Uighur nationality].
AB - OBJECTIVE: To investigate the association of polymorphisms in the apolipoprotein
B gene (APOB) 3'variable number of tandem repeat with natural longevity in the
Xinjiang Uighur nationality people. METHODS: Totally 191 healthy individuals over
90 years and 53 individuals aged 65-70 years were recruited among Xinjiang Uighur
population, the nationality, gender and living area were matched. Genotyping was
performed using polymerase chain reaction-sequence specific primer(PCR-SSP) and
PCR-sequencing. RESULTS: Fourteen alleles were found in the Xinjiang Uighur
nationality population. The frequency of HVE36 and HVE42 in the natural longevity
group were significantly higher than that in the control group (both P<0.05) and
HVE44, HVE46, HVE48 and HVE58 were only found in the natural longevity group.
However, the frequency of HVE26, HVE30 and HVE34 were markedly lower in the
natural longevity group compared to the control group. Logistic regression
analyses revealed that allele L and the genotypes LL were positively associated
with age, whereas the allele S and genotype SS were negatively associated with
age (both P<0.05). Each allele consists of 15 bp tandem repeats with rich-AT by
PCR-sequencing. CONCLUSION: These results indicate that the S allele, and SS
genotype are frail factors in China Uighur natural longevity people, whereas
allele L and genotypes LL are protective factors.
PMID- 17029201
TI - [Genetic polymorphism of HLA-Cw locus in hematopoietic stem cell transplantation
patient and donor population].
AB - OBJECTIVE: To analyze the distribution of genes in HLA-Cw locus from Han
population of China in a large scale, and to provide basic data for further study
on the genetic characteristics of HLA-Cw locus of this population. METHODS:
Totally 1285 unrelated Chinese Han individuals were typed by PCR-SSP, and
statistics was utilized to investigate the distribution rules of detected genes.
RESULTS: Twenty-three HLA-Cw alleles were identified in Chinese Han population,
out of them HLA-Cw*01, *03, *07 and *08 were the commonest genes, which accounted
for frequencies of 0.1529, 0.2385, 0.1747 and 0.1004, respectively. Five genes
which could not be identified by serological method were deaed: HLA-Cw*12, *14,
*15, *16 and *17. Hardy-Weinberg test showed that the observed genetic
polymorphism distribution values were correspondent with the expected (chi
square=73.74, df=98, P>0.5). CONCLUSION: This study may serve a full-scale
scientific genetic parameters of HLA-Cw genes for Chinese Han population studies.
PMID- 17029202
TI - [Association between depression and G72 gene polymorphism].
AB - OBJECTIVE: To investigate the association between G72 gene polymorphisms and
depression,and to probe the difference of G72 gene polymorphisms between
depression with and without mixed family history. METHODS: The polymorphisms of
G72 gene (rs947267 and rs2181953) were detected by PCR technique in 100
depressive patients without mixed family history, 50 depressive patients with
mixed family history and 86 normal controls. RESULTS: (1) The frequencies of
rs947267 genotypes and alleles in female depressive patients without mixed family
history were significant different to the controls (P=0.017 and P=0.008), the OR
scores were 0.300 (A/A, P=0.010), 0.456(A, P=0.008) and 2.195(C, P=0.008)
respectively; but in male patients there were no significant differences to the
controls (P>0.05). (2) The frequencies of rs2181953 genotypes and alleles in the
depressive patients without mixed family history were not significantly different
to the controls regardless of sex (P>0.05). (3) The frequencies of rs947267 and
rs2181953 genotypes and alleles in the depressive patients with mixed family
history were not significantly different to the controls regardless of sex
(P>0.05). CONCLUSION: The G72 gene polymorphism may be associated with female
depressive patients without mixed family history,C allele of rs947267 may be the
risk factor.
PMID- 17029203
TI - [Investigation of RHD 1227A allele in five pedigrees in Zhejiang Han population].
AB - OBJECTIVE: To analysis the genetic mode of Rh DEL phenotype and RHD 1227A allele
in Zhejiang Han population through family investigations. METHODS: Rh DEL
phenotypes were identified by a serologic adsorption-elution method. Two
polymerase chain reaction-sequence specific prime (PCR-SSP) methods which
detectED RHD 1227A allele and Rhesus hybrid box, respectively, and a nucleotide
sequencing method focused on the exon 9 of RHD 1227A allele were employed to
determine the zygosity of RHD allele. RESULTS: All five probands with Rh DEL
phenotype harbored a RHD 1227A allele and had a RHD allele deletion, and they
were RHD 1227A/RHd heterozygote. One of the parent members was found to contain a
RHD 1227A allele and a normal RHD allele in pedigree 1, 2 and 3, respectively.
Thus, they were RHD 1227A/RHD heterozygotes and presented normal D positive
phenotype. The son of proband No 1. inherited the RHD 1227A allele and presented
a normal D positive phenotype due to a RHD 1227A/RHD heterozygote; The offsprings
of proband No. 2, No. 4, and No. 5 did not inherit RHD 1227A allele and presented
a normal D positive phenotype. CONCLUSION: RHD 1227A allele is an important
genetic marker of Rh DEL phenotype; RHD 1227A is recessive to normal RHD allele
and dominant to RHd allele; RHD 1227A allele is an ancestral, but not a
spontaneously mutated allele.
PMID- 17029204
TI - [The investigation of the technology of microcell mediated chromosome transfer
for functional localization of metastasis suppressor genes for liver cancer on
human chromosomes].
AB - OBJECTIVE: In order to seek the functional evidence that there could be
metastatsis suppressor gene for liver cancer on human chromosomes, the objective
of this study is to establish a method of microcell mediated chromosome transfer
(MMCT). METHODS: Human chromosome 8 randomly marked with neo gene was introduced
into highly metastatic rat liver cancer C5F cell line by treating the single
human chromosome donor cells with sequential steps of micronucleation,
enucleation and microcell fusion. Double selections of G418 and HAT were applied
to screen positive microcell hybrids, which were cloned by single cell isolation.
Microcell hybrid clones were confirmed by STS-PCR and WCP-FISH. RESULTS:
Microcell hybrids resistant to HAT and G418 were obtained, from which 15 clones
were obtained by single-cell isolation cloning. STS-PCR and WCP-FISH proved that
human chromosome 8 had been successfully introduced into rat liver cancer cell
line C5F. The human chromosome 8 introduced into C5F was found to have random
loss of chromosome fragments by STS-PCR and consistent recombination with rat
chromosome by WCP-FISH. CONCLUSION: The successfulls introduction of human
chromosome into highly metastatic rat liver cancer cell line has established the
technical basis for functional localization of metastasis suppressor gene(s) for
liver cancer on human chromosomes.
PMID- 17029205
TI - The association of polymorphisms of CDT1 and GMNN gene with the risk of breast
cancer in Chinese women: a case-control analysis.
AB - OBJECTIVE: To investigate the association of polymorphisms of CDT1 and GMNN gene,
two important genes participating in DNA replication, with the risk of sporadic
breast cancer. METHODS: Using polymerase chain reaction-restriction fragment
length polymorphism (PCR - RFLP) and the primer-introduced restriction analysis
(PIRA)-PCR assay to genotype the CDT1 838G/A and GMNN 387C/A polymorphisms in a
case-control study of 427 breast cancer cases and 477 cancer-free controls in a
Chinese population. RESULTS: No significant association of the CDT1 838G/A and
GMNN 387C/A polymorphisms with the risk of breast cancer was found (adjusted
OR:1.16, 95% CI:0.88-1.54 for CDT1 GA+AA genotypes and adjusted OR:0.90, 95%
CI:0.67-1.21 for GMNN CA+AA genotypes). However, in the stratified analyses, a
significant association of CDT1 GA+AA genotypes with breast cancer risk among
subjects with family history of cancer was found (adjusted OR:2.21, 95% CI:1.20
4.09). CONCLUSION: These findings suggest that the CDT1 838G/A and GMNN 387C/A
polymorphisms may not play a major role in the etiology of breast cancer, but
CDT1 variant may have a potential role only in genetically susceptible women.
PMID- 17029206
TI - [Association of the polymorphism of macrophage migration inhibitory factor gene
with coronary heart disease in Chinese population].
AB - OBJECTIVE: Inflammation is involved in the process of coronary heart disease
(CHD). Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine
which can inhibit the random migration of macrophages and concentrate macrophages
at the inflammatory site, and is thought to play an important role in cell
mediated immunity. The present study is to investigate the association of the
173 G/C polymorphism of MIF gene with the outcome of the CHD. METHODS: One
hundred and thirty-eight patients with coronary angiography (CAG) proved CHD were
studied, and 163 healthy matched controls in Guangdong were studied. Patients and
controls were genotyped for a single nucleotide polymorphism in the 5'-flanking
region at position -173 of the MIF gene, using PCR-RFLP analysis, followed by DNA
sequencing identification. RESULTS: Only MIF -173G/G and MIF -173G/C genotypes
were detected in CHD patients and controls. The MIF -173 G allele was detected in
0.966 of normal controls and 0.917 of patients, while MIF -173 C allele was
detected in 0.034 of normal controls and 0.083 of patients. Individuals
possessing a MIF-173*C genotype have an increased risk of CHD (16.7% versus 6.8%)
(OR: 2.764, 95% CI: 1.295-5.899; P= 0.007). CONCLUSION: These results suggest
that MIF -173G /C polymorphism was associated with CHD in Chinese population, the
MIF -173C allele might be a risk factor for CHD in Chinese Han nationality.
PMID- 17029207
TI - [Association and mutation analysis of GLI3 gene in idiopathic congenital talipes
equinovarus].
AB - OBJECTIVE: To explore the association and mutation of GLI3 gene in idiopathic
congenital talipes equinovarus(ICTEV). METHODS: (1) Genotype of 2 single
nucleotide polymorphism (SNP) in 84 idiopathic congenital talipes equinovarus
nuclear pedigree were analyzed by restriction fragment length polymorphism.
Association analysis was directed between single SNP locus and ICTEV through ETDT
software, respectively.(2) Mutation sites in exon 9,10,11,12 of GLI3 gene were
detected in 103 patients with ICTEV by denaturing gradient gel electrophoresis
technique. RESULTS: rs929387ls located in exon 14 of GLI3 gene have transmission
disequilibrium in 84 nuclear pedigrees (P<0.05), and rs846266 located in exon 4
have no transmission disequilibrium (P>0.05). A synonymous mutation in exon 9 was
detected in one patient and his mother. CONCLUSION: There is an association
between GLI3 gene and ICTEV, and exons 9,10,11,12 are not its mutation hot spots.
PMID- 17029208
TI - [Association of genetic polymorphisms in human leukocyte antigen-DQA1 with
intrahepatic cholestasis of pregnancy in Chengdu district].
AB - OBJECTIVE: To explore the relationship between human leukocyte antigen-DQA1 (HLA
DQA1) allele gene polymorphism and intrahepatic cholestasis of pregnancy (ICP).
METHODS: Forty-five patients with ICP, eighteen ICP families, forty-five normal
pregnant women and eighteen normal control families were tested for HLA-DQA1
allele gene polymorphism by polymerase chain reaction with sequence-specific
primer (PCR-SSP) method. RESULTS: The frequency of HLA-DQA1*0301 in normal
pregnant women was markedly higher than that in the ICP group (P>0.05). No
significant differences were observed between the frequencies of other detected
HLA-DQA1 alleles in both groups. The analysis of feto-maternal or couples sharing
of the HLA-DQA1 alleles showed that no significant differences were observed
between the two groups. CONCLUSION: The above findings suggest that there is no
significant association between the genetic polymorphisms in HLA-DQA1 and ICP in
Chengdu district; HLA-DQA1*0301 may be a protective gene against ICP. It may
prevent the development of ICP.
PMID- 17029209
TI - [Avoiding the interference of ABCD1 pseudogenes in the molecular diagnosis of X
linked adrenoleukodystrophy by double amplification refractory mutation system].
AB - OBJECTIVE: To avoid the interference of ABCD1 pseudogenes, the amplification
refractory mutation system (ARMS) was used to analyze the mutation of ABCD1 gene
in the molecular diagnosis of X-linked adrenoleukodystrophy (ALD). METHODS: The
upstream primers (wild primer and mutation primer) were designed according to the
principle of primer-design in ARMS. In addition, a common downstream primer was
designed in the same way to discriminate ABCD1 gene from its prologous
pseudogenes. The genomic DNA isolated from the peripheral blood leukocytes of the
family members and normal controls was amplified by PCR. RESULTS: In double ARMS,
a specific product of 107bp could be amplified from genomic DNA of the patient
with R617C mutation in ABCD1 gene and his mother, while the same product was not
found when the genomic DNA of the patient's father and normal controls was used.
Thus, the interference of ABCD1 pseudogenes in molecular diagnosis of ALD was
excluded successfully at genomic DNA level. CONCLUSION: Double ARMS is a quick
and effective method to eliminate the interference of the pseudogenes in
detecting ABCD1 gene mutations.
PMID- 17029210
TI - [Correlation between the polymorphism of platelet glycoprotein GPIb alpha Kozak
gene and transient ischemic attack].
AB - OBJECTIVE: Genic susceptibility could increase the risk of transient ischemic
attack (TIA). The objective of this study is to investigate the relationship
between the polymorphism of platelet glycoprotein GPIb alpha Kozak gene and TIA
in Qindao Han population. METHODS: The polymorphisms of platelet glycoprotein
GPIb alpha Kozak gene -5T/C in TIA patients and normal control were detected with
sequence-specific primers polymerase chain reaction (PCR-SSP). RESULTS: The
prevalence of the CC genotype and C alleles were significantly higher in TIA
patients than in the control group (P<0.05). The positive correlation between C
allele and TIA was showed by logistic regression analysis (P=0.016). CONCLUSION:
The -5T/C polymorphism of the platelet glycoprotein GPIb alpha Kozak gene is
implicated in the pathogenesis of TIA. C allele is an independent risk factor for
TIA.
PMID- 17029211
TI - [Methylation status of FHIT gene in plasma and expression of FHIT gene in cancer
tissue of cervical cancer patients].
AB - OBJECTIVE: To explore the methylation status of 5' CpG island of fragile
histidine triad (FHIT) gene in plasma and the expression of FHIT protein in
cancer tissue of cervical cancer patients. METHODS: Methylation-specific PCR (MS
PCR) was employed to examine methylation of FHIT gene in 151 plasma samples
before treatment. The immunohistochemistry was used to the expression of FHIT
protein in cancer tissues. RESULTS: CpG island methylation of FHIT was detected
in 31.13% of plasma samples. The expression of FHIT protein was decreased or
discarded in 59.60% of cervical cancer tissues. Among them 47.78% was included in
methylation positive samples. CONCLUSION: CpG island methylation of FHIT gene in
plasma plays an important role on cervical cancer, which results in decreased
expression of FHIT protein. It can be used to diagnose and evaluate the effect of
treatment to cervical cancers.
PMID- 17029212
TI - [Analysis of the non-Hodgkin lymphoma's clinic and blood marrow cytogenetics].
AB - OBJECTIVE: To analyze the relationship among cytogenetics, hematopathology,
morphology, clinic tumor index and prognosis of the non-Hodgkin lymphoma(NHL)
patients. METHODS: Cytogenetics analysis of bone marrow cells was performed by
direct method and 24 h culture method in 20 cases of NHL. Serous P53 protein was
detected in all patients. RESULTS: Out of the twenty NHL patients, eight had bone
marrow infiltration, and nine were found with abnormal karyotype: three were
chromosome number abnormalities, one was t(14,18)(q32;q21), one was 14q+, two
were t(8;14)(q24;q32), two were t(8;14)(q24;q32) with additional changes of
chromosome. The serous P53 protein of patients with abnormal karyotype was
significantly higher than that with normal karyotype. CONCLUSION: t(8;14)
(q24;q32) is the most classic translocation in NHL, The patients with this
karyotype have worse prognosis. The increase of mutant serous P53 relates to
abnormal karyotype, and the patients with high mutant P53 level in serum also
have worse prognosis.
PMID- 17029213
TI - [The investigation and analysis of the Rh blood type distribution in four kinds
of the minority nationalities (Miao, Buyi, Dong and Shui) in Guizhou, China].
AB - OBJECTIVE: To comprehend the Rh blood type distribution and the gene frequency in
four main kinds of the minority nationalities in Guizhou, China, so as to supply
a scientific foundation for guiding the prevention and cure against the Rh
hemolysis illness. METHODS: The irrelative individual blood of the four kinds of
the minority nationalities (Miao, Buyi, Dong and Shui) in Guizhou was randomly
collected in complete group style and the Rh blood type was identified and
analyzed. RESULTS: Totally 15,992 minority nationality people were inspected and
checked, and 4851 persons of Han nationality people were chosen as controls.
Fifty-one persons were proven as Rh (D)negative individuals, in which, d gene
frequency of Miao nationality population was 0.0474 and the Rh negative rate was
0.22%, d gene frequency of Buyi nationality population was 0.0602 and the Rh
negative rate was 0.36%, d gene frequency of Dong nationality population was
0.0378 and the Rh negative rate was 0.14%, d gene frequency of Shui nationality
population was 0.0307 and the Rh negative rate was 0.09%. d gene frequency of Han
nationality population was 0.0574 and the Rh negative rate was 0.33%. In the four
minority nationality populations, there was a common characteristic of the
highest percentage of expressional type, CCDee type (52.47%-59.66%). At the same
time, in the gene frequency of the four minority nationality populations, the CDe
frequency was the highest: Miao nationality 0.7244, Buyi nationality 0.7389, Dong
nationality 0.7410 and Shui nationality 0.7743. CONCLUSION: The Rh blood type
distribution characteristic of the four minority nationality population, Miao,
Dong, Buyi and Shui in Guizhou, is similar to that of the minority population in
Southern China. The Rh negative rate of Miao, Dong and Shui nationality
populations is lower than that of the Han nationality population(0.33%), only the
Rh negative rate of Buiyi nationality population is closer or even higher than
that of the Han nationality population. So that,the hemolysis illness frequency
in the Rh newborn baby of Guizhou minority nationality population is not high.
PMID- 17029214
TI - [Polymorphism of five short tandem repeat loci on chromosome X in Hebei Han
population].
AB - OBJECTIVE: To investigate the polymorphism of DXS6801, DXS6809, DXS7423, DXS7424,
DXS9902 five loci in Hebei Han population. METHODS: The PCR products were
detected by the polyacrylamide gel electrophresis and DNA sequencing analysis.
RESULTS: Among 114 irrelative males and 118 irrelative females from Hebei Han
population, 31 alleles were found in the 5 loci. One hundred and one haplotypes
of the male were detected and the haplotype diversity reached 0.9975. CONCLUSION:
The five loci are relatively abundant in polymorphic information for
identification and paternity test. And the obtained data of Hebei Han population
can be applied to the X-short tandem repeat genetic data bank.
PMID- 17029215
TI - [hPARP1 genetic polymorphism in southern Chinese Han and Miao populations].
AB - OBJECTIVE: To study hPARP1 genetic polymorphism in southern Chinese Han and Miao
populations. METHODS: Blood samples from 187 and 210 southern healthy Han and
Miao populations were collected. The mutations of exons 12,13,16 and 17 of hPARP1
gene were investigated by PCR-single-strand conformation polymorphism(SSCP).
RESULTS: Fragments of 253 bp,313 bp,175 bp,362 bp within exons 12,13,16 and 17
respectively of hPARP1 gene were amplified by multiple PCR. An SSCP variant in
exons 12,13,16 and 17 of PARP1 gene in 187 healthy Han and 210 healthy Miao
individuals was identified. Seven single-base substitutions compared with the
sequence of PARP1 gene were identified: a T to C transition in exon 12
(Phe548Ser), a G to T transition in exon 13 (Ala683Ser), a G to T transition in
exon 16 (Asp798Tyr), and a A to G transition in exon 17 (His808Arg). CONCLUSION:
There were polymorphism sites in exons 12,13,16,17 of hPARP1 gene in southern
Chinese Han and Miao populations; these results may be useful for the
establishment of PARP1 genotyping, and these newly described PARP1 alleles would
be advantageous indicators for population studies.
PMID- 17029216
TI - Novel epigenetically deregulated genes in testicular cancer include homeobox
genes and SCGB3A1 (HIN-1).
AB - Testicular germ cell tumours (TGCTs) are classified into two main histological
subgroups: seminomas and non-seminomas. The latter comprise several subtypes:
embryonal carcinomas, yolk sac tumours, choriocarcinomas, and teratomas. These
embryonal and extra-embryonal-like differentiation lineages represent a
caricature of early normal development, and inactivation of gene expression
through promoter hypermethylation may therefore be of particular importance in
germ cell tumourigenesis. The promoter methylation status of ten candidate genes
CDH13, DLX6, EMX2, HOXA9, HOXB5, MSX1, MSX2, RASSF1A, RUNX3, and SCGB3A1 (alias
HIN-1)-was assessed by methylation-specific PCR in seven intratubular germ cell
neoplasias and 55 primary TGCTs. Furthermore, by a discovery-based global
approach, comparing cDNA microarray expression profiles of two germ cell tumour
cell lines before and after treatment with the demethylating agent 5-aza-2'
deoxycytidine, a gene list of potentially epigenetic targets was identified, from
which CGGBP1, CGRRF1, SMARCC2, SORBS1, and XPA were analysed further. Overall,
the non-seminomas were significantly more often methylated than were seminomas (p
< 0.001). The three most frequently methylated genes among this subtype were
SCGB3A1 (54%), RASSF1A (29%), and HOXA9 (26%). CDH13 and HOXB5 were methylated at
low frequencies (10-15%), and EMX2, MSX1, RUNX3, SORBS1, and XPA only rarely
(<10%). In conclusion, this study has identified several novel epigenetically
deregulated target genes in TGCT development, including homeobox genes and
SCGB3A1, suggesting that epigenetic inactivation of key genes in normal
development also has an important role in TGCTs.
PMID- 17029217
TI - Disrupted galectin-3 causes non-alcoholic fatty liver disease in male mice.
AB - Galectin-3, a beta-galactoside-binding animal lectin, is a multifunctional
protein. Previous studies have suggested that galectin-3 may play an important
role in inflammatory responses. Non-alcoholic fatty liver disease (NAFLD) is
increasingly recognized as a liver condition that may progress to end-stage liver
disease and based on the known functions of galectin-3, it was hypothesized that
galectin-3 might play a role in the development of NAFLD. Thus, this study
investigated the role of galectin-3 in NAFLD by comparing galectin-3 knockout
(gal3(-/-)) mice and wild-type (gal3(+/+)) mice. The livers of gal3(-/-) male
mice at 6 months of age histologically displayed mild to severe fatty change. The
liver weight per body weight ratio, serum alanine aminotransferase levels, liver
triglyceride levels, and liver lipid peroxide in gal3(-/-) mice were
significantly increased compared with those in gal3(+/+) mice. Furthermore, the
hepatic protein levels of advanced glycation end-products (AGE), receptor for AGE
(RAGE), and peroxisome proliferator-activated receptor gamma (PPARgamma) were
increased in gal3(-/-) mice relative to gal3(+/+) mice. In conclusion, this study
suggests that the absence of gal3 can cause clinico-pathological features in male
mice similar to those of NAFLD.
PMID- 17029218
TI - The presence of an intronic deletion in p73 and high levels of ZEB1 alter the
TAp73/DeltaTAp73 ratio in colorectal carcinomas.
AB - TAp73 variants largely mimic p53 suppressor activities, while DeltaTAp73 forms
act as oncogenes through the inactivation of p53 and TAp73. The present study
analysed how TAp73 and DeltaTAp73 levels might be affected by the presence of a
73 bp deletion in a regulatory region of p73. The clinical relevance of this
deletion was also examined. ZEB1 can bind to the region repressing p73
transcription in vitro. The relationship between ZEB1 and p73 variant expression
levels was studied in the context of this deletion and the levels of the ZEB1
cofactors p300 and CtBP. Tumour and normal tissue from 81 colorectal cancer
patients was analysed to evaluate firstly the levels of TAp73, DeltaTAp73
(DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73), ZEB1, p300, and CtBP by quantitative
real-time RT-PCR, and secondly the presence of the 73 bp deletion. Tumour
characteristics were examined in each patient. Suppressor and oncogenic isoforms
of p73 were co-up-regulated in tumour tissues. Overexpression of p73 variants was
associated with adverse tumour features. The 73 bp deletion was present in 40% of
the patients and was associated with adverse pathological parameters of the
tumours and also with TAp73 down-regulation. In those cases harbouring the
deletion, the levels of ZEB1 and those of DeltaEx2p73, DeltaEx2/3p73, and
DeltaNp73 correlated directly. Variations in the concentration of p300 affected
the observed correlations between ZEB1 and the different p73 variants. In
conclusion, in colorectal cancer, the 73 bp deletion in the first intron of the
p73 gene and different expression levels of ZEB1 and p300 may act in concert to
affect the ratio of TAp73/DeltaTAp73 forms, favouring p73 oncogenic variants. In
addition, up-regulation of p73 oncogenic isoforms predicts a poor prognosis based
on its relationship with advanced tumour stage.
PMID- 17029219
TI - SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular
carcinoma.
AB - Both Secreted Protein Acidic and Rich in Cysteine (SPARC) and Hevin are
multifunctional matricellular glycoproteins. Recent experimental studies
suggested that Hevin and SPARC together diminish angiogenesis, but their
significance in hepatocellular carcinoma (HCC) remains unclear. This study aimed
to correlate SPARC and Hevin expression with angiogenesis and clinicopathological
features in HCC. SPARC and Hevin protein and mRNA expression in HCC specimens
were assessed by immunostaining, immunoblotting, and quantitative reverse
transcriptase-polymerase chain reaction. Tumour microvessel density (MVD) was
assessed by CD34 immunostaining. The role of SPARC and Hevin in HCC was further
assessed in an in vivo nude mice xenograft model. Both SPARC and Hevin mRNA
levels were significantly higher in tumours than in non-tumourous livers. A
significant correlation between tumour SPARC and Hevin mRNA levels was found.
Moreover, SPARC protein localized in the tumour sinusoidal area correlated
significantly with Hevin protein localized in HCC cells. Truncated forms of SPARC
and Hevin proteins were detected in clinical samples. Truncated SPARC protein
localized in the tumour sinusoidal area correlated significantly with tumour MVD.
On the other hand, overexpression of full-length SPARC in tumour xenografts in
athymic nude mice significantly delayed tumour growth, and this delay was related
to a decrease in tumour angiogenesis. Expression of Hevin protein within HCC
cells was related to the presence of tumour encapsulation and the absence of
hepatitis B surface antigen in clinical samples. Overexpression of Hevin in
tumour xenografts also significantly delayed tumour growth. In conclusion, this
study has shown that SPARC and Hevin are upregulated in HCC compared with non
tumourous liver, and that they are inter-related at both mRNA and protein levels.
Moreover, both SPARC and Hevin were related to HCC angiogenesis and tumour
progression.
PMID- 17029220
TI - Differential expression and pathological significance of autocrine motility
factor/glucose-6-phosphate isomerase expression in human lung carcinomas.
AB - To clarify the involvement of autocrine motility factor (AMF) in the phenotype
and biological profiles of human lung carcinomas, we analysed protein and mRNA
expression in a total of 180 cases. Immunohistochemistry revealed positive
staining in 67.2%, with the highest frequency in squamous cell carcinoma (SCC;
90.8%) and the lowest in small cell carcinoma (SmCC; 27.8%). In SCC, the staining
frequency and intensity correlated with the degree of morphological
differentiation. Generally, the expression levels in immunoblotting analysis
corresponded well with immunohistochemical positivity. However, there was less
agreement between protein and mRNA levels: in SmCC and large cell carcinomas
(LCCs), mRNA showed higher, but protein showed lower expression. Among non-small
cell lung carcinomas (NSCLCs), AMF protein levels correlated inversely with
tumour size, but tumours exhibiting lymph node metastasis showed higher mRNA
expression. In cultured lung carcinoma cells which comprised all histological
subtypes, AMF was detected in the lysates of all ten cell lines. Secreted AMF
protein was detected in the conditioned media from six cell lines, most of which
were SmCC or LCC. Thus, a particular subset of lung carcinomas secrete AMF, which
may promote cell motility via autocrine stimulation through its cognate receptor
and cause the biological aggressiveness seen in SmCC and LCC. Moreover, treatment
by proteasome inhibitors resulted in increased cellular AMF in five cell lines,
suggesting that intracellular AMF levels are regulated by both secretion and
proteasome-dependent degradation. In conclusion, AMF was detected in a major
proportion of lung carcinomas, and may play a part not only in proliferation
and/or progression of the tumours, but also, possibly, in the differentiation of
SCC. Furthermore, higher mRNA expression may be related to the high metastatic
potential of NSCLC and increased protein secretion, leading to a more aggressive
phenotype, such as the invasiveness of SmCC and LCC.
PMID- 17029221
TI - Methyltestosterone efficiently induces male development in the self-fertilizing
hermaphrodite fish, Kryptolebias marmoratus.
AB - A hermaphrodite fish, Kryptolebias marmoratus, is the only known vertebrate that
reproduces by self-fertilization. In nature, males have been rarely observed. Low
temperature treatment during late embryonic stages is known to induce males but
its efficacy is variable. Here we report that 17alpha-methyltestosterone (MT)
treatment of the embryos converted most of the fish to males. We examined a time
course of this male induction with histological and marker gene expression
analyses. Oogenesis started in the gonads of the control embryo at hatching;
spermatogenesis did not start until two months after hatching. In the MT-treated
fish, oogenesis started initially as in the control but stopped completely within
one month after hatching. Instead, spermatogonial proliferation started earlier
than in the control fish and progressed to full spermatogenesis. Expression
profiles of the sex-specific marker genes corresponded well with histological
observations. From one month after hatching, expression of an oocyte-specific
marker, figalpha, and a testicular somatic cell marker, dmrt1, started to
increase in the control and in the MT-treated fish, respectively.
PMID- 17029223
TI - Real-time rigid body motion correction and shimming using cloverleaf navigators.
AB - Subject motion during scanning can greatly reduce MRI image quality and is a
major reason for discarding data in both clinical and research scanning. The
quality of the high-resolution structural data used for morphometric analysis is
especially compromised by subject movement because high-resolution scans are of
longer duration. A method is presented that measures and corrects rigid body
motion and associated first-order shim changes in real time, using a pulse
sequence with embedded cloverleaf navigators and a feedback control mechanism.
The procedure requires a 12-s preliminary mapping scan. A single-path, 4.2-ms
cloverleaf navigator is inserted every repetition time (TR) after the readout of
a 3D fast low-angle shot (FLASH) sequence, requiring no additional RF pulses and
minimally impacting scan duration. Every TR, a rigid body motion estimate is made
and a correction is fed back to adjust the gradients and shim offsets. Images are
corrected and reconstructed on the scanner computer for immediate access.
Correction for between-scan motion can be accomplished by using the same
reference map for each scan repetition. Human and phantom tests demonstrated a
consistent improvement in image quality if motion occurred during the
acquisition.
PMID- 17029224
TI - Dynamic coil selection for real-time imaging in interventional MRI.
AB - MR-guided intravascular interventions require image update rates of up to 10
images per second, which can be achieved using parallel imaging. However,
parallel imaging requires many coil elements, which increases reconstruction
times and thus compromises real-time image reconstruction. In this study a
dynamic coil selection (DCS) algorithm is presented that selects a subset of
receive coils to reduce image reconstruction times. The center-of-sensitivity
coordinates and the relative signal intensities are determined for each coil in a
prescan. During the intervention m coils are selected for reconstruction using a
coil ranking based on the distance to the current slice or catheter position. In
a phantom experiment for m = 6, an optimal signal-to-background ratio (SBR) was
achieved and foldover artifacts were avoided. In three animal experiments
involving catheter manipulation in the aorta and the right heart chamber, the
anatomy was successfully visualized at frame rates of about 5 Hz using active
catheter tracking.
PMID- 17029225
TI - T2 measurement and quantification of glutamate in human brain in vivo.
AB - The proton NMR transverse relaxation time T(2) of glutamate (Glu) in human brain
was measured by means of spectrally selective refocusing at 3.0 T in vivo. An
81.4-ms-long dual-band Gaussian 180 degrees RF pulse, designed for refocusing at
2.35 and 3.03 ppm, was employed within point-resolved spectroscopy (PRESS) to
generate the Glu C4-proton target multiplet and the total creatine (tCr) singlet.
Six optimal echo times (TEs) between 128 and 380 ms were selected from numerical
analysis of the filtering performance for effective detection of the Glu signal
with minimal contamination from glutamine (Gln), N-acetylaspartate (NAA), and
glutathione (GSH). The magnetization of Glu and tCr was extracted from spectral
fitting of experimental and calculated spectra. Apparent T(2) values of Glu and
tCr were estimated as 201 +/- 18 and 164 +/- 12 ms for the medial prefrontal (PF)
cortex, and 198 +/- 22 and 169 +/- 15 ms (mean +/- SD, N = 5) for the left
frontal (LF) cortex, respectively. With water segmentation data, the
magnetization values of Glu and tCr of the two adjacent voxels, calculated from
the T(2) values and spectra following the thermal equilibrium magnetization, were
combined to give the Glu and tCr concentrations as 10.37 +/- 1.06 and 8.87 +/-
0.56 mM for gray matter (GM), and 5.06 +/- 0.57 and 5.16 +/- 0.45 mM (mean +/-
SD, N = 5) for white matter (WM), respectively.
PMID- 17029227
TI - An algorithm for the automated quantitation of metabolites in in vitro NMR
signals.
AB - The quantitation of metabolite concentrations from in vitro NMR spectra is
hampered by the sensitivity of peak positions to experimental conditions. The
quantitation methods currently available are generally labor intensive and cannot
readily be automated. Here, an algorithm is presented for the automatic time
domain analysis of high-resolution NMR spectra. The TARQUIN algorithm uses a set
of basis functions obtained by quantum mechanical simulation using predetermined
parameters. Each basis function is optimized by subdividing it into a set of
signals from magnetically equivalent spins and varying the simulated chemical
shifts of each of these groups to match the signal undergoing analysis. A novel
approach to the standard multidimensional minimization problem is introduced
based on evaluating the fit resulting from different permutations of possible
chemical shifts, obtained from one-dimensional searches. Results are presented
from the analysis of (1)H proton magic angle spinning spectra of cell lines
illustrating the robustness of the method in a typical application. Simulation
was used to investigate the biggest peak shifts that can be tolerated.
PMID- 17029226
TI - T2* measurement during first-pass contrast-enhanced cardiac perfusion imaging.
AB - First-pass contrast-enhanced (CE) myocardial perfusion imaging will experience
T(2) (*) effects at peak concentrations of contrast agent. A reduction in the
signal intensity of left ventricular (LV) blood due to T(2) (*) losses may effect
estimates of the arterial input function (AIF) used for quantitative perfusion
measurement. Imaging artifacts may also result from T(2) (*) losses as well as
off-resonance due to the bolus susceptibility. We hypothesized that T(2) (*)
losses would not be significant for measurement of the AIF in full-dose studies
using a short echo time (TE = 0.6 ms). The purpose of this study was to directly
measure T(2) (*) in the LV cavity during first-pass perfusion. For single-dose Gd
DTPA (0.1 mmol/kg at 5 ml/s), the LV blood pool T(2) (*) had a mean value of 9 ms
(N = 10) at peak enhancement. Distortion of the AIF due to T(2) (*) signal
intensity loss will be less than 10% using TE = 0.6 ms.
PMID- 17029228
TI - Three-dimensional prepolarized magnetic resonance imaging using rapid acquisition
with relaxation enhancement.
AB - Prepolarized MRI (PMRI) with pulsed electromagnets has the potential to produce
diagnostic quality 0.5- to 1.0-T images with significantly reduced cost,
susceptibility artifacts, specific absorption rate, and gradient noise. In PMRI,
the main magnetic field cycles between a high field (B(p)) to polarize the sample
and a homogeneous, low field (B(0)) for data acquisition. This architecture
combines the higher SNR of the polarizing field with the imaging benefits of the
lower field. However, PMRI can only achieve high SNR efficiency for volumetric
imaging with 3D rapid imaging techniques, such as rapid acquisition with
relaxation enhancement (RARE) (FSE, TSE), because slice-interleaved acquisition
and longitudinal magnetization storage are both inefficient in PMRI. This paper
demonstrates the use of three techniques necessary to achieve efficient, artifact
free RARE in PMRI: quadratic nulling of concomitant gradient fields,
electromotive force cancelation during field ramping, and phase compensation of
CPMG echo trains. This paper also demonstrates the use of 3D RARE in PMRI to
achieve standard T(1) and fat-suppressed T(2) contrast in phantoms and in vivo
wrists. These images show strong potential for future clinical application of
PMRI to extremity musculoskeletal imaging and peripheral angiography.
PMID- 17029229
TI - In vivo MRI of cancer cell fate at the single-cell level in a mouse model of
breast cancer metastasis to the brain.
AB - Metastasis (the spread of cancer from a primary tumor to secondary organs) is
responsible for most cancer deaths. The ability to follow the fate of a
population of tumor cells over time in an experimental animal would provide a
powerful new way to monitor the metastatic process. Here we describe a magnetic
resonance imaging (MRI) technique that permits the tracking of breast cancer
cells in a mouse model of brain metastasis at the single-cell level. Cancer cells
that were injected into the left ventricle of the mouse heart and then delivered
to the brain were detectable on MR images. This allowed the visualization of the
initial delivery and distribution of cells, as well as the growth of tumors from
a subset of these cells within the whole intact brain volume. The ability to
follow the metastatic process from the single-cell stage through metastatic
growth, and to quantify and monitor the presence of solitary undivided cells will
facilitate progress in understanding the mechanisms of brain metastasis and tumor
dormancy, and the development of therapeutics to treat this disease.
PMID- 17029230
TI - Proton MRI as a noninvasive tool to assess elastase-induced lung damage in
spontaneously breathing rats.
AB - Elastase-induced changes in lung morphology and function were detected in
spontaneously breathing rats using conventional proton MRI at 4.7 T. A single
dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline)
was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid
signals were detected in the lungs 24 hr after administration of elastase and
resolved within 2 weeks. These results correlated with perivascular edema and
cellular infiltration observed histologically. Reductions in MRI signal intensity
of the lung parenchyma, and increases in lung volume were detected as early as 2
weeks following elastase administration and remained uniform throughout the
study, which lasted 8 weeks. Observations were consistent with air trapping
resulting from emphysema detected histologically. In a separate experiment,
animals were treated daily intraperitoneally (i.p.) with all-trans-retinoic acid
(ATRA; 500 microg/kg body weight) or its vehicle (triglyceride oil) starting on
day 21 after elastase administration and continuing for 12 days. Under these
conditions, ATRA did not elicit a reversal of elastase-induced lung damage as
measured by MRI and histology. The present approach complements other validated
applications of proton MRI in experimental lung research as a method for
assessing drugs in rat models of respiratory diseases.
PMID- 17029231
TI - Microvessel density estimation in the human brain by means of dynamic contrast
enhanced echo-planar imaging.
AB - Animal studies have shown that in vivo estimates of microvessel density in the
brain may be obtained from an MRI-measurable index (Q) provided that a
sufficiently high dose of an intravascular paramagnetic contrast agent is
employed. Q is determined from the shifts in the transverse relaxation rates
induced by the contrast agent, and a high dose is required for the validity of
analytic expressions relating Q to the microvessel density. However, the steady
state imaging techniques used in these prior investigations are not appropriate
for humans, as the required contrast agent dose is too large. Here results of a
pilot study with three subjects are reported. The results suggest that reliable Q
measurements can be performed in the human brain at 1.5 T by using an interleaved
spin-echo (SE)/gradient-echo (GE) echo-planar imaging (EPI) sequence and a bolus
injection of a triple dose of Gd-DTPA. Lower- and upper-bound estimates for the
microvessel density were derived from the Q-values, and were found to be in
reasonable accord with previously cited values determined by histology.
PMID- 17029232
TI - Behavior of ordered sodium in enzymatically depleted cartilage tissue.
AB - The onset of cartilage tissue disorders can be characterized by a loss of
proteoglycans (PGs) and diagnosed by contrast-enhanced proton ((1)H) MRI
techniques, as well as sodium MRI. The behavior of sodium located in anisotropic
environments, is examined as a function of cartilage degeneration. PGs are
proteolytically depleted from the cartilage samples, which gives rise to a
decrease of the ordered sodium content. More surprisingly, however, the residual
quadrupolar couplings are shown to increase with increasing depletion levels.
Since the residual quadrupolar couplings are intimately related to local order
and anisotropic motion, measuring their distribution in cartilage may provide
insight into the structural changes that occur within the tissue upon
degradation. In this study relatively mild orientational dependence of the
couplings was found. Little or no free sodium was observed in the cartilage
specimens under study.
PMID- 17029233
TI - Magnetic resonance angiography reveals therapeutic enlargement of collateral
vessels induced by VEGF in a murine model of peripheral arterial disease.
AB - PURPOSE: To quantify spontaneous and therapeutic arteriogenesis in vivo in a
murine model of peripheral arterial disease using magnetic resonance angiography.
MATERIALS AND METHODS: Male, 8-12-week-old, C57/BL6 mice underwent femoral artery
ligation; 21 days later, 2 mg/kg recombinant murine VEGF165, formulated for slow
release, was injected into the ipsilateral gastrocnemius. The spontaneous
(following ligation) and therapeutic (following vascular endothelial growth
factor (VEGF)) formation of collateral vessels was quantified using 3D magnetic
resonance angiography on a small-bore 4.7T system. Therapeutically induced
angiogenesis and blood flow were quantified using an in situ anti-platelet
endothelial cell adhesion molecule (PECAM) 1 radioimmunoassay and radiolabeled
microsphere deposition, respectively. RESULTS: Spontaneous arteriogenesis was
visible in all animals five days after ligation. VEGF treatment doubled the
arteriogenic response five days after treatment compared to vehicle (cross
sectional area of vessels: 0.96 vs. 0.46 mm2, P<0.01). VEGF also induced
angiogenesis (PECAM1 levels 191% of vehicle, P<0.05) and increased blood flow
specific to the injection site (57 vs. 7 mL/minute/100 g, P<0.05). CONCLUSION:
The presented methodology allowed in vivo quantification of spontaneous
arteriogenesis in a murine model of peripheral arterial disease and demonstrated
that therapeutic enlargement of collateral vessels is possible with VEGF.
PMID- 17029234
TI - Novel approach for alpha-helical topology prediction in globular proteins:
generation of interhelical restraints.
AB - The protein folding problem represents one of the most challenging problems in
computational biology. Distance constraints and topology predictions can be
highly useful for the folding problem in reducing the conformational space that
must be searched by deterministic algorithms to find a protein structure of
minimum conformational energy. We present a novel optimization framework for
predicting topological contacts and generating interhelical distance restraints
between hydrophobic residues in alpha-helical globular proteins. It should be
emphasized that since the model does not make assumptions about the form of the
helices, it is applicable to all alpha-helical proteins, including helices with
kinks and irregular helices. This model aims at enhancing the ASTRO-FOLD protein
folding approach of Klepeis and Floudas (Journal of Computational Chemistry
2003;24:191-208), which finds the structure of global minimum conformational
energy via a constrained nonlinear optimization problem. The proposed topology
prediction model was evaluated on 26 alpha-helical proteins ranging from 2 to 8
helices and 35 to 159 residues, and the best identified average interhelical
distances corresponding to the predicted contacts fell below 11 A in all 26 of
these systems. Given the positive results of applying the model to several
protein systems, the importance of interhelical hydrophobic-to-hydrophobic
contacts in determining the folding of alpha-helical globular proteins is
highlighted.
PMID- 17029235
TI - Structural comparison of oxidized and reduced FKBP13 from Arabidopsis thaliana.
AB - AtFKBP13, an immunophilin in the chloroplast thylakoid lumen, participates in
redox-regulatory processes via a pair of conserved disulfide bonds that are
present at the N- and C-termini of the protein. Characterization of this protein
by structural and biochemical analysis has revealed a novel mechanism of redox
regulation in the thylakoid lumen. The protein is active in its oxidized form but
is inactivated after reduction by the thioredoxin system. This is in sharp
contrast with the regulation of biosynthetic enzymes in the stroma of the
chloroplast, where reduction of enzymes by thioredoxin activates their function.
To understand how the reduced form of AtFKBP13 is stabilized and how reduction of
the cysteine residues affects the molecular properties of the enzyme, we
determined the crystal structure of reduced AtFKBP13 at 1.88 A. Comparison of the
reduced structure and the oxidized form that we published earlier shows
rearrangements in redox site regions, readjustments of hydrogen-bonding
interactions and the secondary structure of the active site residues 50-53, and
reduced accessibility of the catalytic residues involved in the peptidyl proline
isomerase (PPIase) activity of this enzyme. We propose that redox-linked changes
in the secondary structure of the PPIase domain are responsible for significant
functional differences in this protein in the reduced and oxidized states.
PMID- 17029236
TI - Chemodosimetry of in vivo tumor liposomal drug concentration using MRI.
AB - Effective cancer chemotherapy depends on the delivery of therapeutic drugs to
cancer cells at cytotoxic concentrations. However, physiologic barriers, such as
variable vessel permeability, high interstitial fluid pressure, and heterogeneous
perfusion, make it difficult to achieve that goal. Efforts to improve drug
delivery have been limited by the lack of noninvasive tools to evaluate
intratumoral drug concentration and distribution. Here we demonstrate that tumor
drug concentration can be measured in vivo using T(1)-weighted MRI, following
systemic administration of liposomes containing both drug (doxorubicin (DOX)) and
contrast agent (manganese (Mn)). Mn and DOX concentrations were calculated using
T(1) relaxation times and Mn:DOX loading ratios, as previously described. Two
independent validations by high-performance liquid chromatography (HPLC) and
histologic fluorescence in a rat fibrosarcoma (FSA) model indicate a concordant
linear relationship between DOX concentrations determined using T(1) and those
measured invasively. This method of imaging exhibits potential for real-time
evaluation of chemotherapeutic protocols and prediction of tumor response on an
individual patient basis.
PMID- 17029237
TI - Phototoxicity and fluorotoxicity combine to alter the behavior of neutrophils in
fluorescence microscopy based flow adhesion assays.
AB - The use of fluorescent probes that allow visualization of leukocyte-endothelial
cell (EC) interactions has greatly informed our understanding of leukocyte
recruitment. However, effects of these agents on the biological functions of
leukocytes are poorly described, leading to concerns about the interpretation of
such data. Here we used two flow-based neutrophil adhesion assays to compare the
effects of phase contrast illumination (PCI) with high intensity illumination
(HII) used for fluorescent microscopy, in the presence or absence of five
commonly used fluorochromes. Isolated neutrophils were either (1) perfused across
P-selectin to establish a population of rolling cells, which were subsequently
activated with fMLP; or (2) perfused across EC activated with TNF-alpha. In the
absence of fluorescent dyes, HII did not affect levels of leukocyte adhesion;
however, subsequent neutrophil behavior was dramatically altered when compared
with cells under PCI, for example, dramatically reducing their migration
velocities. In the presence of fluorescent dyes, the effects of HII were
exacerbated, although the precise nature of the biological effects of these
probes was agent specific. Thus, for the first time, our experiments describe the
effects of fluorescent microscopy on the separate stages of the neutrophil
recruitment process and reveal a previously unsuspected effect of HII on
neutrophil migration.
PMID- 17029238
TI - Thermovoltaic properties of hornet silk.
AB - In silk from the larval silk caps of the Oriental hornet Vespa orientalis
(Hymenoptera, Vespinae), temperature-dependent changes in the electric voltage
have been recorded, with rise in the voltage occurring mainly upon rise in the
temperature between 10-36 degrees C. The peak voltage was measured between 32-38
degrees C and attained 240-360 mV, but with further increase in temperature, the
voltage decreased, dropping to 0 mV at about 45-50 degrees C. Upon second
measurement (of same silk specimen), the voltage peak usually occurred later (by
8-9 degrees C) and at higher temperature than in the first measurement.
Continuous measurements during warming up to 30 degrees C followed by cooling
down to 15 degrees C yielded an hysteresis between the warming "line" and the
cooling "line", the former often straight and the latter usually curved.
Maintaining the silk specimen at a fixed temperature for a prolonged period
(hours) initially causes the voltage to rise, then remain steady, and finally
drop. Boiling the silk caps in tap water for 7-10 min exerts some changes in the
silk properties, mainly a decrease in voltage level. The general behavior of the
silk suggests that it is a polymer endowed with the qualities of an organic
semiconductor. The various properties of the larval silk are discussed in great
detail.
PMID- 17029239
TI - Analysis of changes in optical fibers during arc-fusion splicing by use of
quantitative phase imaging.
AB - A non-interferometric imaging technique in conjunction with Abel inversion is
used to directly and quantitatively examine the changes in optical fibers due to
the heating produced during arc-fusion splicing as a function of fusion arc
parameters. Phase images in the vicinity of a fusion splice are obtained using
Quantitative Phase Microscopy, allowing the refractive-index change to be
reconstructed with high spatial resolution. This simple, nondestructive method
confirms that, for a fixed arc current, while the fusion time increases, the
refractive-index of both fiber cores within the fusion region decreases in
magnitude, the core region broadens, and the axial gradient decreases.
PMID- 17029240
TI - Anatomy of the frontal gland and ultramorphology of the frontal tube in the
soldier caste of species of Nasutitermitinae (Isoptera, Termitidae).
AB - All termite species (Isoptera) are eusocial. These insects live in societies
where the division of labor is a predominant characteristic, conditioned by the
presence of castes with different morphology, ontogeny, and development. The
soldier caste is unique among social insects and it is responsible for colony
defense. Soldiers belonging to the Nasutitermitinae subfamily are very peculiar,
since they may be polymorphic and present a nasus in addition to either developed
or vestigial mandibles. The defensive secretions of soldiers of the neotropical
Nasutitermitinae have been the aim of several chemical studies, but few data
exist concerning the anatomy and histology of the exocrine glands. This article
presents a comparative study on the anatomy of the frontal gland of soldiers of
several Nasutitermitinae species: Syntermes dirus (Burmeister), Syntermes nanus
(Constantino), Constrictotermes cyphergaster (Silvestri), Nasutitermes corniger
(Motschulsky) and Velocitermes heteropterus (Silvestri), with emphasis on the
ultramorphology and ultrastructure of the frontal tube.
PMID- 17029241
TI - Identification of a new subfamily of HNH nucleases and experimental
characterization of a representative member, HphI restriction endonuclease.
AB - The restriction endonuclease (REase) R. HphI is a Type IIS enzyme that recognizes
the asymmetric target DNA sequence 5'-GGTGA-3' and in the presence of Mg(2+)
hydrolyzes phosphodiester bonds in both strands of the DNA at a distance of 8
nucleotides towards the 3' side of the target, producing a 1 nucleotide 3'
staggered cut in an unspecified sequence at this position. REases are typically
ORFans that exhibit little similarity to each other and to any proteins in the
database. However, bioinformatics analyses revealed that R.HphI is a member of a
relatively big sequence family with a conserved C-terminal domain and a variable
N-terminal domain. We predict that the C-terminal domains of proteins from this
family correspond to the nuclease domain of the HNH superfamily rather than to
the most common PD-(D/E)XK superfamily of nucleases. We constructed a three
dimensional model of the R.HphI catalytic domain and validated our predictions by
site-directed mutagenesis and studies of DNA-binding and catalytic activities of
the mutant proteins. We also analyzed the genomic neighborhood of R.HphI homologs
and found that putative nucleases accompanied by a DNA methyltransferase (i.e.
predicted REases) do not form a single group on a phylogenetic tree, but are
dispersed among free-standing putative nucleases. This suggests that nucleases
from the HNH superfamily were independently recruited to become REases in the
context of RM systems multiple times in the evolution and that members of the HNH
superfamily may be much more frequent among the so far unassigned REase sequences
than previously thought.
PMID- 17029242
TI - Crystal structure of XC5357 from Xanthomonas campestris: a putative
tetracenomycin polyketide synthesis protein adopting a novel cupin subfamily
structure.
PMID- 17029243
TI - The crystal structure of XC847 from Xanthomonas campestris: a 3'-5'
oligoribonuclease of DnaQ fold family with a novel opposingly shifted helix.
PMID- 17029245
TI - Pulmonary dysfunction in pediatric hematopoietic stem cell transplant patients:
non-infectious and long-term complications.
AB - Pulmonary complications are among the most frequently encountered sequelae of
pediatric hematopoietic stem cell transplantation (HSCT). Non-infectious
complications are becoming increasingly more common in this unique population.
This review addresses the diagnosis and management of non-infectious
manifestations of lung disease in pediatric HSCT patients and briefly discusses
the long-term pulmonary function of childhood HSCT survivors.
PMID- 17029244
TI - Modulation of connexin expression and gap junction communication in astrocytes by
the gram-positive bacterium S. aureus.
AB - Gap junctions establish direct intercellular conduits between adjacent cells and
are formed by the hexameric organization of protein subunits called connexins
(Cx). It is unknown whether the proinflammatory milieu that ensues during CNS
infection with S. aureus, one of the main etiologic agents of brain abscess in
humans, is capable of eliciting regional changes in astrocyte homocellular gap
junction communication (GJC) and, by extension, influencing neuron homeostasis at
sites distant from the primary focus of infection. Here we investigated the
effects of S. aureus and its cell wall product peptidoglycan (PGN) on Cx43, Cx30,
and Cx26 expression, the main Cx isoforms found in astrocytes. Both bacterial
stimuli led to a time-dependent decrease in Cx43 and Cx30 expression; however,
Cx26 levels were elevated following bacterial exposure. Functional examination of
dye coupling, as revealed by single-cell microinjections of Lucifer yellow,
demonstrated that both S. aureus and PGN inhibited astrocyte GJC. Inhibition of
protein synthesis with cyclohexamide (CHX) revealed that S. aureus directly
modulates, in part, Cx43 and Cx30 expression, whereas Cx26 levels appear to be
regulated by a factor(s) that requires de novo protein production; however, CHX
did not alter the inhibitory effects of S. aureus on astrocyte GJC. The p38 MAPK
inhibitor SB202190 was capable of partially restoring the S. aureus-mediated
decrease in astrocyte GJC to that of unstimulated cells, suggesting the
involvement of p38 MAPK-dependent pathway(s). These findings could have important
implications for limiting the long-term detrimental effects of abscess formation
in the brain which may include seizures and cognitive deficits.
PMID- 17029247
TI - Validity and consequence of informed consent in pediatric bone marrow
transplantation: The parental experience.
AB - BACKGROUND: Conditions supporting a high quality of consent for pediatric bone
marrow transplantation (BMT) are suboptimal given the complexity of the
procedure, lack of options, and parent emotional duress. We studied if parents
perceived choice when consenting to BMT, if they felt the consent provided was
valid, and how the consent process affected them. METHODS: Telephone or face-to
face interviews were recorded using a semi-structured interview outline.
Interview transcripts were anonymized, and independently analyzed by three
reviewers. RESULTS: Twenty parents of twelve children participated, including
five bereaved parents. There were no differences in patient transplant
characteristics between the eligible and study groups. Divorced or separated
parents were underrepresented in the participant group. Fifteen parents felt
personally compelled to consent; most (18) denied feeling external medical
pressure to do so. All parents felt their consent was valid and most reported
adequate levels of freedom, capacity, and information. Expectations formulated
during the consent process strongly influenced parents' experience post-BMT. Good
communication during consent contributed to trust and therapeutic alliance with
physicians following BMT. Late parental stress and anxiety were periodic, but
very high in some families. CONCLUSIONS: Parents feel consent for pediatric BMT
is valid, despite feeling personally compelled to consent. Strategies aimed at
nurturing hope and realistic expectations may assist in improving the consent
process, while diminishing long-term stressors.
PMID- 17029246
TI - Pulmonary dysfunction in pediatric hematopoietic stem cell transplant patients:
overview, diagnostic considerations, and infectious complications.
AB - Pulmonary complications are among the most common and serious sequelae seen in
hematopoietic stem cell transplantation (HSCT) recipients. This two-part review
addresses the incidence and impact of pulmonary complications in pediatric HSCT
patients. In this first part we review the available data for the use of
diagnostic modalities in this population, including flexible bronchoscopy with
bronchoalveolar lavage (BAL) and open lung biopsy (OLB). We also review the many
infectious pulmonary complications that may occur in pediatric HSCT recipients,
utilizing the traditional chronologic divisions of neutropenic phase (0-30 days
following HSCT), early phase (30-100 days), and late phase (>100 days).
PMID- 17029248
TI - Risk factors for extraocular relapse following enucleation after failure of
chemoreduction in retinoblastoma.
AB - OBJECTIVE: To assess the outcome and determine risk factors for extraocular
relapse in patients with retinoblastoma who had been enucleated after failure of
chemoreduction. METHODS: Retrospective study (1995-2002) at three institutions.
Pathological risk factors (PRF) were defined as invasion of the anterior segment,
choroid, post-laminar optic nerve, subarachnoid space, or sclera according to the
local pathology report. Extraocular relapse was defined as an event. RESULTS: One
hundred twenty-two patients were included (17 had bilateral enucleation).
Chemoreduction included vincristine, carboplatin, and etoposide (n=80, 65.6%),
vincristine, and carboplatin (n=17, 13.9%), or carboplatin (n=25, 20.5%). Thirty
five also received external beam radiotherapy (28.7%). PRF included: 39 with
choroidal involvement, 9 with anterior segment, 9 with scleral, and 2 with post
laminar optic nerve with subarachnoid invasion. Adjuvant chemotherapy was given
to eight patients (6.5%) because of scleral invasion. Four patients had an
extraocular relapse after enucleation, two of whom survive after intensive
treatment including stem cell rescue. Five-year probability of event-free
survival is 0.96. Only scleral invasion and bilateral enucleation were
significantly associated with extraocular relapse. CONCLUSIONS: The risk of
extraocular relapse is low after enucleation following failure of chemoreduction.
Patients who underwent bilateral enucleation and those with scleral invasion are
at higher risk of extraocular relapse.
PMID- 17029249
TI - The role of angiotensin II in stress urinary incontinence: A rat model.
AB - AIMS: Pharmacological treatment for stress urinary incontinence (SUI) is limited
to the use of non-selective alpha-agonists, which are often ineffective. Non
adrenergic mechanisms have also been implicated in urethral closure, including
angiotensin II (Ang-II), which has been demonstrated throughout the urinary
tract. We investigate the role of Ang-II in urethral tone in a rat model of SUI.
METHODS: Abdominal leak point pressure (ALPP) and retrograde urethral pressure
profilometry (RLPP) were measured in 70 female virgin rats. Thirty rats underwent
pudendal nerve injury (PNT), 30 had circumferential urethrolysis (U-Lys), and 10
had sham surgery. Rats received daily doses of Angiotensin Type 1 (AT-1) receptor
inhibitor (20 mg/kg), Angiotensin Type 2 (AT-2) receptor antagonist (10 mg/kg),
or Ang-II (2 mg/kg). RESULTS: Following U-Lys, RLPP and ALPP decreased from 21.4
+/- 2.0 and 39.2 +/- 3.3 mm Hg, to 13.1 +/- 1.5 and 21.6 +/- 1.9 mmHg,
respectively (P < 0.01). After PNT, RLPP, and ALPP decreased from 21.0 +/- 1.6
and 41.9 +/- 3.0 mmHg to 13.1 +/- 1.5 and 24.7 +/- 3.3 mmHg, respectively (P <
0.01). AT-1 inhibitor caused significant decrease in RLPP and ALPP from 21.0 +/-
6.2 and 41.8 +/- 9.4 mmHg, to 12.0 +/- 3.8 and 25.6 +/- 6.6 mmHg, respectively (P
< 0.01). Likewise, AT-2 treatment reduced RLPP and ALPP from 21.4 +/- 6.3 and
40.1 +/- 1.7 mmHg, to 13.5 +/- 5.7 and 31.0 +/- 7.2 mmHg, respectively (P <
0.01). Following surgery, Ang-II administration restored RLPP and ALPP to
baseline presurgical values. CONCLUSIONS: AT-1 and AT-2 receptor inhibition
significantly lowers urethral resistance, comparable to either neurogenic or
urethrolytic injury. Ang-II treatment restored urethral tone in rats with
intrinsic sphincter dysfunction. Ang II appears to serve a functional role in the
maintenance of urethral tone and stress continence.
PMID- 17029250
TI - Influence of temperature on urethra to bladder micturition reflex in the awake
ewe.
AB - AIMS: The flow of fluid along the urethra is known to facilitate detrusor
contraction during micturition. This reflex, previously described in awake ewes,
helps to achieve complete bladder emptying. In anesthetized cats, another urethra
to bladder reflex involving urethral cold receptors has been described. The aim
of this study was to investigate whether the urethral reflex first described in
awake ewes could also be temperature-dependent. METHODS: Experiments were
performed on 10 healthy ewes. Urethral flows were performed by injecting 10 ml
saline (ranging from 17 to 43 degrees C) at the level of the proximal urethra.
Catheterization of the bladder was performed so that detrusor pressure was
continually recorded during the experiments. RESULTS: Urethral flows using body
temperature saline (37-39 degrees C) consistently evoked detrusor contraction.
Urethral flows using saline at temperatures between 40 and 43 degrees C induced
detrusor contractions that were not significantly different from those observed
at 37-39 degrees C. Urethral flows using saline at temperatures below 37-39
degrees C (17-36 degrees C) resulted in a weaker or absent detrusor contraction.
CONCLUSIONS: In ewes, we have shown that urethral to bladder micturition reflex
involving mechanoreceptors is decreased at temperatures below the physiological
range. It is suggested that transient receptor potential vanilloid cation
channels (e.g., TRPV4 which is activated by sheer/stress flows at near-body
temperature) could be involved in this urethra to bladder reflex. In humans, this
reflex has hardly been described and is still a matter of debate. Our results
reinforce that its full investigation may require systematic use of a range of
saline flows at different temperatures.
PMID- 17029252
TI - Modular neuropile organization in the Drosophila larval brain facilitates
identification and mapping of central neurons.
AB - Elucidating how neuronal networks process information requires identification of
critical individual neurons and their connectivity patterns. For this purpose, we
used the third-instar Drosophila larval brain and applied reverse-genetic tools,
immunolabeling procedures, and 3D digital reconstruction software. Consistent
topological definition of neuropile compartments in the larval brain can be
obtained through simple fluorescence-immunolabeling methods. The modular
neuropiles can be used as a fiducial framework for mapping the projection
patterns of individual neurons labeled with green fluorescent protein (GFP). GFP
labeled neurons often exhibit dendrite-like arbors as well as clustered varicose
terminals on neurite branches that innervate identifiable neuropile compartments.
We identified candidate cholinergic interneurons in genetic mosaic brains that
overlap with the larval optic nerve terminus. By using the neuropile framework,
we demonstrate that the candidate visual interneurons are not a subset of the
previously identified circadian pacemaker neurons that also contact the larval
optic nerve terminus; they may represent parallel pathways in the processing of
visual inputs. Thus, in the Drosophila larval brain, modular neuropiles can be
used as a framework for systematically identifying, mapping, and classifying
interneurons; understanding their roles in behavior can then be pursued further.
PMID- 17029251
TI - Galpha encoding gene family of the malaria vector mosquito Anopheles gambiae:
expression analysis and immunolocalization of AGalphaq and AGalphao in female
antennae.
AB - To initiate a comprehensive investigation of chemosensory signal transduction
downstream of odorant receptors, we identified and characterized the complete set
of genes that encode G-protein alpha subunits in the genome of the malaria vector
mosquito An. gambiae. Data are provided on the tissue-specific expression
patterns of 10 corresponding aga-transcripts in adult mosquitoes and pre-imago
developmental stages. Specific immunoreactivity in chemosensory hairs of female
antennae provides evidence in support of the participation of a subset of
AGalphaq isoforms in olfactory signal transduction in this mosquito. In contrast,
AGalphao is localized along the flagellar axon bundle but is absent from
chemosensory sensilla, which suggests that this G-protein alpha subunit does not
participate in olfactory signal transduction.
PMID- 17029253
TI - Estradiol-induced modulation of estrogen receptor-beta and GABA within the adult
neocortex: a potential transsynaptic mechanism for estrogen modulation of BDNF.
AB - Estrogen influences brain-derived neurotrophic factor (BDNF) expression in the
neocortex. However, BDNF-producing cortical neurons do not express detectable
levels of nuclear estrogen receptors; instead, the most abundant cortical nuclear
estrogen receptor, ER-beta, is present in GABAergic neurons, prompting us to test
the hypothesis that estrogen effects on BDNF are mediated via cortical inhibitory
interneurons. Adult female ovariectomized rats were provided acute estrogen
replacement and the number of cortical GABA, ER-beta, and ER-beta/GABA double
labeled neurons was examined. Within 48 hours of injection of 17-beta-estradiol,
the number of perirhinal neurons double-labeled for ER-beta/GABA was reduced by
28% (P<0.01 compared to vehicle-treated ovariectomized controls), and all cells
expressing detectable levels of GABA were reduced by 19% (P<0.01). To investigate
potential relationships between estrogen receptors, GABAergic neurons, and BDNF
expressing cells, brain sections were double- or triple-labeled for ER-beta,
GABAergic, and BDNF immunomarkers. The findings indicated that ER-beta-bearing
inhibitory neurons project onto other GABAergic neurons that lack nuclear
estrogen receptors; these inhibitory neurons in turn innervate BDNF-expressing
excitatory cells. High estrogen states reduce cortical GABA levels, presumably
releasing inhibition on BDNF-expressing neurons. This identifies a putative two
step transsynaptic mechanism whereby estrogen availability modulates expression
of inhibitory transmitters, resulting in increased BDNF expression.
PMID- 17029254
TI - Transitory uptake of serotonin in the developing sensory pathways of the common
marmoset.
AB - Serotonin (5-HT) affects brain development during sensitive developmental
periods. In rodents, transient sites of high affinity capture of 5-HT were
demonstrated in the primary sensory neurons and in the sensory thalamocortical
afferents. This uptake is required to adjust 5-HT receptor stimulation during the
formation of sensory maps. To determine whether similar mechanisms exist in
primates, we analyzed staged embryos and postnatal pups in the common marmoset
(total gestation time, 142 days). Immunocytochemical analyses were performed
using antisera to 5-HT, to the serotonin transporter (SERT), and to the vesicular
monoamine transporter (VMAT2). 5-HT, SERT, and VMAT2 labeled the raphe neurons
and their terminal network from embryonic day (E)70 to adulthood. In addition,
from E70-130 VMAT2 and SERT were observed in all the sensory cranial nerves, the
olfactory nerve, the gustatory, the trigeminal, the auditory fibers, in the
retinal ganglion cells, and the optic tract up to the lateral geniculate nucleus
and the superior colliculus. All the spinal sensory ganglia and their peripheral
sensory branches were labeled. Accumulation of 5-HT was observed in all the
sensory neurons expressing SERT and the corresponding axon tracts. Since these
neurons were missing tryptophan hydroxylase (TPH), the synthesizing enzyme for 5
HT, they most likely accumulated 5-HT through the action of the amine
transporters, as has been shown in rodents. No transient expression of 5-HT
markers was detectable in the sensory thalamocortical axons at any of the ages
examined. Thus, the existence of 5-HT uptake in nonserotoninergic neurons appears
to be a conserved feature in primates, although the topographic extent of this
transient expression is more restricted than that previously demonstrated in
rodents.
PMID- 17029256
TI - Bone morphogenetic protein-4 expression in the adult rat brain.
AB - Bone morphogenetic protein-4 (BMP4) is a member of the transforming growth factor
beta (TGF-beta) superfamily and plays important roles in multiple biological
events. Although BMP4 expression has been well described in the early development
of the central nervous system (CNS), little information is available on its
expression in the adult CNS. Therefore, we investigated BMP4 expression in the
adult rat CNS by using immunohistochemistry. BMP4 is intensely expressed in most
neurons and their dendrites. In addition, intense BMP4 expression was also
observed in the neuropil of the gray matters where high plasticity is reported,
such as the molecular layer of the cerebellum and the superficial layer of the
superior colliculus. Furthermore, we found that astrocytes also express BMP4
protein. These data indicate that BMP4 is more widely expressed throughout the
adult CNS than previously reported, and its continued abundant expression in the
adult brain strongly supports the idea that BMP4 plays pivotal roles also in the
adult brain.
PMID- 17029257
TI - Primary and secondary sensory trigeminal projections in a cyprinid teleost, carp
(Cyprinus carpio).
AB - Primary and secondary sensory trigeminal projections were studied by means of
tract-tracing methods in a cyprinid teleost, the carp. Tracer injections into the
trigeminal nerve root labeled terminals in the ipsilateral principal sensory
trigeminal nucleus, descending trigeminal nucleus, medial funicular nucleus,
facial lobe, and medial part of posterior lateral valvular nucleus. The principal
sensory trigeminal nucleus is considered a major origin of the secondary sensory
trigeminal projections in teleosts. To investigate the secondary sensory
trigeminal projections, tracer injections were performed into the principal
sensory trigeminal nucleus. The present study suggests that the principal sensory
trigeminal nucleus projects to the bilateral ventromedial thalamic nucleus,
periventricular pretectal nucleus, stratum album centrale of the optic tectum,
caudomedial region of lateral preglomerular nucleus, ventrolateral nucleus of
semicircular torus, medial part of rostral and posterior lateral valvular
nucleus, oculomotor nucleus, trochlear nucleus, trigeminal motor nucleus, facial
motor nucleus, superior and inferior reticular formation, descending trigeminal
nucleus, medial funicular nucleus, inferior olive, and to the contralateral
sensory trigeminal nucleus. These observations indicate that the primary and
secondary trigeminal sensory projections of a cyprinid teleost, the carp, are
similar to those in percomorph teleosts.
PMID- 17029258
TI - Expression of protein kinase C-substrate mRNAs in the basal ganglia of adult and
infant macaque monkeys.
AB - We performed in situ hybridization histochemistry on the monkey basal ganglia to
investigate the mRNA localization of three protein kinase C substrates (GAP-43,
MARCKS, and neurogranin), of which expression plays a role in structural changes
in neurites and synapses. Weak hybridization signals for GAP-43 mRNA and intense
signals for both MARCKS and neurogranin mRNAs were observed in the adult
neostriatum. All three of the mRNAs were expressed in both substance P-positive
direct pathway neurons and enkephalin-positive indirect pathway neurons. In the
nucleus accumbens, the hybridization signals for the three mRNAs were weaker than
those in the neostriatum. Double-label in situ hybridization histochemistry in
the neostriatum revealed that GAP-43 and neurogranin mRNAs were expressed in a
subset of MARCKS-positive neurons. While intense hybridization signals for MARCKS
mRNA were observed in all of the other basal ganglia regions such as the globus
pallidus, substantia innominata, subthalamic nucleus, and substantia nigra,
intense signals for GAP-43 mRNA were restricted to the substantia innominata and
substantia nigra pars compacta. No signal for neurogranin mRNA was observed in
the basal ganglia regions outside the neostriatum and the nucleus accumbens.
These results indicate that the protein kinase C substrates are abundant in some
specific connections in cortico-basal ganglia circuits. Developmental analysis
showed that the expression level in the putamen and nucleus accumbens, but not in
the caudate nucleus, was higher in the infant than in the adult, suggesting that
synaptic maturation in the caudate nucleus occurs earlier than that in the
putamen and nucleus accumbens.
PMID- 17029259
TI - Longitudinal study of the motor response to levodopa in Parkinson's disease.
AB - In this prospective study of 34 patients with Parkinson's disease, measurements
of the short duration levodopa motor response have been performed in defined off
states at 3 yearly intervals over a mean period of 11.4 years from the point of
commencement of levodopa treatment. Twenty-two patients were still available for
study; 10 had died and 2 were lost to follow-up. The levodopa motor response
amplitude increases over the first 5 years of treatment, and thereafter, on and
off scores worsen in parallel with conservation of the response. Patients who
developed motor fluctuations within the first 5 years of treatment had, on
average, a stronger response to levodopa with significantly better on phase motor
function (P = 0.003). Although the proportion of "midline" motor disability
(affecting gait, balance, and cranial motor function) increases with time, these
deficits do not actually become unresponsive to levodopa. Patients who developed
dementia had a significantly more rapid decline in motor function. The latest
graph of serial scores for the whole cohort shows an upward curving or
exponential increase in motor disability after the first decade of treatment.
Applying a notional untreated disability line to this graph--an estimate of the
disability that would have accrued if drugs had never been given--we suggest that
the long-duration response to levodopa eventually runs down with disease
progression.
PMID- 17029260
TI - Hypoperfusion of the auditory and prefrontal cortices in Parkinsonian patients
with verbal hallucinations.
AB - We examined patients with and without auditory hallucinations, using n-isopropyl
p-[123I]iodoamphetamine single photon emission computed tomographic imaging. We
assessed verbal hallucinations in the present study: patients with nonverbal
auditory hallucinations were excluded. A total of 11 patients with verbal and
visual hallucinations and 17 patients with visual hallucinations only were
enrolled. Patients with both verbal and visual hallucinations revealed
significant hypoperfusion in the bilateral prefrontal cortex and right superior
temporal gyrus compared to patients with visual hallucinations only. There were
no significant hyperperfusion in patients with verbal plus visual hallucinations.
These results may support the release hallucination theory in verbal
hallucinations of Parkinson's disease, although another explanations may be more
appropriate and further studies are required.
PMID- 17029261
TI - Age at menopause predicts age at onset of Parkinson's disease.
AB - We investigated the association between age at onset of Parkinson's disease (PD)
and fertile life characteristics in 145 women. Linear regression analyses showed
a significant correlation between age at PD onset and age at menopause (P =
0.003), between age at PD onset and fertile life duration (P = 0.008), and a
nonsignificant correlation between PD onset and cumulative duration of
pregnancies (P = 0.23). These results support the possible role of estrogens in
PD.
PMID- 17029263
TI - Neurosurgical treatment of tremor in mitochondrial encephalopathy.
AB - A 53-year-old woman underwent several ischemic stroke-like episodes and later
developed incomplete, bilateral ophthalmoplegia, left vision deterioration, and
bilateral tremor. The clinical course, laboratory data, and muscle histology led
to a diagnosis of mitochondrial encephalomyopathy. No other etiology could be
identified in the background of her disabling bilateral postural-kinetic tremor.
As this tremor did not respond to pharmacological therapy, left thalamotomy and
subsequently right thalamic deep brain stimulator (DBS) implantation were
performed, which resulted in an excellent clinical outcome. The Fahn-Tolosa-Marin
Tremor Rating Scale improved from 110 to 11 points. This case suggests that the
rare tremor caused by mitochondrial encephalopathy may be treated long-term with
either thalamotomy or thalamic DBS implantation.
PMID- 17029262
TI - Differential responses to branched and unsaturated aliphatic hydrocarbons in the
rat olfactory system.
AB - In an effort to understand mammalian olfactory processing, we have been
describing the responses to systematically different odorants in the glomerular
layer of the main olfactory bulb of rats. Previously, we demonstrated
chemotopically organized and distinct olfactory responses to a homologous series
of straight-chained alkanes that consisted of purely hydrocarbon structures,
indicating that hydrocarbon chains could serve as molecular features in the
combinatorial coding of odorant information. To better understand the processing
of hydrocarbon odorants, we now have examined responses to other types of
chemical changes in these kinds of molecules, namely, branching and carbon-carbon
bond saturation. To this end, we used the [14C]2-deoxyglucose method to determine
glomerular responses to a group of eight-carbon branched alkane isomers,
unsaturated octenes (double-bonded), and octynes (triple-bonded). In contrast to
the differential responses we observed previously for straight-chained alkanes of
differing carbon number, the rat olfactory system was not particularly sensitive
to these variations in branching and bond saturation. This result was unexpected,
given the distinct molecular conformations and property profiles of the odorants.
The similarity in activity patterns was paralleled by a similarity in spontaneous
perceptual responses measured using a habituation assay. These results
demonstrate again the functional relationship between bulbar activity patterns
and odor perception. The results further suggest that the olfactory system does
not respond equally to all aspects of odorant chemistry, functioning as a
specific, rather than a general, chemical analysis system.
PMID- 17029264
TI - Striatal dopaminergic neurons are lost with Parkinson's disease progression.
AB - Increased numbers of dopaminergic neurons are described in the striatum of
patients with Parkinson's disease. In postmortem striatal tissue from Parkinson's
disease patients with short disease duration (< or =8 years), the number of
dopaminergic neurons is approximately four times that in patients with long
duration (> or =16 years). The data suggest the possibility that the presence of
large numbers of these striatal dopaminergic neurons may be harmful and may
accelerate the disease process. Alternatively, these neurons may be lost to the
disease process.
PMID- 17029266
TI - Cerebral autoregulation is preserved in multiple system atrophy: A transcranial
Doppler study.
AB - Patients with multiple system atrophy (MSA) present large changes in blood
pressure (BP) due to autonomic disturbances. We analyzed how this change may
influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of
arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV)
(transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of
age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to
oscillations in mean BP was studied in the supine position by cross-spectral
analysis of mean BP and mean MCA BFV. The DCA was also studied during the
decrease in BP the first seconds when standing up from a sitting position by the
assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV
ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid
frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active
autoregulation in response to larger changes in BP. Changes in CR reflecting the
rate of autoregulation, when standing did not differ between the two groups.
These data suggest that dynamic cerebral autoregulation is preserved in MSA.
PMID- 17029267
TI - Patterns of mechanical energy change in tetrapod gait: pendula, springs and work.
AB - Kinematic and center of mass (CoM) mechanical variables used to define
terrestrial gaits are compared for various tetrapod species. Kinematic variables
(limb phase, duty factor) provide important timing information regarding the
neural control and limb coordination of various gaits. Whereas, mechanical
variables (potential and kinetic energy relative phase, %Recovery, %Congruity)
provide insight into the underlying mechanisms that minimize muscle work and the
metabolic cost of locomotion, and also influence neural control strategies. Two
basic mechanisms identified by Cavagna et al. (1977. Am J Physiol 233:R243-R261)
are used broadly by various bipedal and quadrupedal species. During walking,
animals exchange CoM potential energy (PE) with kinetic energy (KE) via an
inverted pendulum mechanism to reduce muscle work. During the stance period of
running (including trotting, hopping and galloping) gaits, animals convert PE and
KE into elastic strain energy in spring elements of the limbs and trunk and
regain this energy later during limb support. The bouncing motion of the body on
the support limb(s) is well represented by a simple mass-spring system. Limb
spring compliance allows the storage and return of elastic energy to reduce
muscle work. These two distinct patterns of CoM mechanical energy exchange are
fairly well correlated with kinematic distinctions of limb movement patterns
associated with gait change. However, in some cases such correlations can be
misleading. When running (or trotting) at low speeds many animals lack an aerial
period and have limb duty factors that exceed 0.5. Rather than interpreting this
as a change of gait, the underlying mechanics of the body's CoM motion indicate
no fundamental change in limb movement pattern or CoM dynamics has occurred.
Nevertheless, the idealized, distinctive patterns of CoM energy fluctuation
predicted by an inverted pendulum for walking and a bouncing mass spring for
running are often not clear cut, especially for less cursorial species. When the
kinematic and mechanical patterns of a broader diversity of quadrupeds and bipeds
are compared, more complex patterns emerge, indicating that some animals may
combine walking and running mechanics at intermediate speeds or at very large
size. These models also ignore energy costs that are likely associated with the
opposing action of limbs that have overlapping support times during walking. A
recent model of terrestrial gait (Ruina et al., 2005. J Theor Biol, in press)
that treats limb contact with the ground in terms of collisional energy loss
indicates that considerable CoM energy can be conserved simply by matching the
path of CoM motion perpendicular to limb ground force. This model, coupled with
the earlier ones of pendular exchange during walking and mass-spring elastic
energy savings during running, provides compelling argument for the view that the
legged locomotion of quadrupeds and other terrestrial animals has generally
evolved to minimize muscle work during steady level movement.
PMID- 17029265
TI - Innervation of orexin/hypocretin neurons by GABAergic, glutamatergic or
cholinergic basal forebrain terminals evidenced by immunostaining for presynaptic
vesicular transporter and postsynaptic scaffolding proteins.
AB - Orexin/hypocretin (Orx) neurons are critical for the maintenance of waking in
association with behavioral arousal and postural muscle tone, since with their
loss narcolepsy with cataplexy occurs. Given that basal forebrain (BF) neurons
project to the hypothalamus and play important diverse roles in sleep/wake
states, we sought to determine whether acetylcholine (ACh), glutamate (Glu),
and/or GABA-releasing BF neurons innervate and could thereby differentially
regulate the Orx neurons. From discrete injections of biotinylated dextran amine
(BDA, 10,000 MW) into the magnocellular preoptic nucleus (MCPO) and substantia
innominata (SI) in the rat, BDA-labeled fibers projected to the lateral
hypothalamus (LH), perifornical area (PF), and dorsomedial hypothalamus (DMH),
where approximately 41%, approximately 11%, and 9% of Orx-positive (+) neurons
were respectively contacted in each region. Employing triple fluorescent staining
for Orx, BDA, and presynaptic vesicular (V) transporters (T), we found that only
4% of the innervated Orx+ neurons in the LH were contacted by BDA+[VAChT+]
terminals, whereas approximately 31% and approximately 67% were respectively
contacted by BDA+[VGluT2+] and BDA+[VGAT+] terminals. In 3D-rendered and rotated
confocal images, we confirmed the latter contacts and examined staining for
postsynaptic proteins PSD-95, a marker for glutamatergic synapses, and gephyrin,
a marker for GABAergic synapses, that were located on Orx+ neurons facing BDA
labeled terminals in approximately 20% and approximately 50% of contacts,
respectively. With such synaptic input, BF glutamatergic neurons can excite Orx
neurons and thus act to maintain behavioral arousal with muscle tone, whereas
GABAergic neurons can inhibit Orx neurons and thus promote behavioral quiescence
and sleep along with muscle atonia.
PMID- 17029268
TI - The tri-segmented limbs of therian mammals: kinematics, dynamics, and self
stabilization--a review.
AB - The evolution of therian mammals is to a large degree marked by changes in their
motion systems. One of the decisive transitions has been from the sprawled, bi
segmented to the parasagittal, tri-segmented limb. Here, we review aspects of the
tri-segmented limb in locomotion which have been elucidated in our research
groups in the last 10 years. First, we report the kinematics of the tri-segmented
therian limb from mouse to elephant in order to explore general principles of the
therian limb configuration and locomotion. Torques will be reported from a
previous paper (Witte et al., 2002. J Exp Biol 205:1339-1353) for a better
understanding of the anti-gravity work of all limb joints. The stability of a
limb in z-configuration will be explained and its advantage with respect to other
potential solutions from modeling will be discussed. Finally, we describe how the
emerging concept of self-stability can be explained for a tri-segmented leg
template and how it affects the design of the musculoskeletal system and the
operation of legs during locomotion. While locomotion has been considered as
mainly a control problem in various disciplines, we stress the necessity to
reduce control as much as possible. Central control can be cheap if the limbs are
"intelligent" by means of their design. Gravity-induced movements and self
stability seem to be energy-saving mechanisms.
PMID- 17029269
TI - Correlation of symmetrical gaits and whole body mechanics: debunking myths in
locomotor biodynamics.
AB - Independent maturation of gait (Hildebrand) and whole body mechanics (Cavagna et
al.) traditions in locomotor analyses has led to conflicting terminology. Re
evaluation of these traditions yields three primary insights. First, walking and
running should be recognized by their fundamentally different mechanics. Because
duty factor fails to consistently distinguish these mechanics, its use in
discriminating walks from runs should be abandoned in preference to parameters
that more accurately reflect the movements of the center of mass (COM; phase
difference in external mechanical energy or Froude number). Second, "trot" should
be reserved as a descriptor of a particular footfall pattern. This and all gait
terms lack explicit information about limb compliance and thus COM movements.
Third, symmetrical gait definitions should be broadened to reflect the four
primary footfall patterns: the lateral-couplet dominated pattern of the pace, the
diagonal-couplet dominated pattern of the trot and the more independent
sequencing of footfalls of the two singlefoots. Intermediate gaits (perennially
confusing and a mouthful to pronounce) are thereby subsumed by these four
discrete gaits. Confusion between gait terminologies would be avoided if limb
phase were consistently reported.
PMID- 17029270
TI - Periventricular efferent neurons in the optic tectum of rainbow trout.
AB - The efferent connections and axonal and dendritic morphologies of periventricular
neurons were examined in the optic tectum of rainbow trout to classify
periventricular efferent neurons in salmonids. Among the target nuclei of tectal
efferents, tracer injections to the following four structures labeled
periventricular neurons: the area pretectalis pars dorsalis (APd), nucleus
pretectalis superficialis pars magnocellularis (PSm), nucleus ventrolateralis of
torus semicircularis (TS), and nucleus isthmi (NI). Two types of periventricular
neurons were labeled by injections to the APd. One of them had an apical dendrite
ramifying at the stratum fibrosum et griseum superficiale (SFGS), with an axon
that bifurcated into two branches at the stratum griseum centrale (SGC), and the
other had an apical dendrite ramifying at the SGC. Two types of periventricular
neurons were labeled after injections to the TS. One of them had an apical
dendrite ramifying at the boundary between the stratum opticum (SO) and the SFGS,
and the other had dendritic branches restricted to the stratum album centrale or
stratum periventriculare. Injections to the PSm and NI labeled periventricular
neurons of the same type with an apical dendrite ramifying at the SO and a
characteristic axon that split into superficial and deep branches projecting to
the PSm and NI, respectively. This cell type also possessed axonal branches that
terminated within the tectum. These results indicate that periventricular
efferent neurons can be classified into at least five types that possess type
specific axonal and dendritic morphologies. We also describe other tectal neurons
labeled by the present injections.
PMID- 17029271
TI - Distribution and differentiation of microglia in the human encephalon during the
first two trimesters of gestation.
AB - We describe the topographical distribution of microglial subpopulations during
development of the human diencephalon and telencephalon. Brains from embryos and
fetuses age 5-23.5 gestational weeks (gw) were subjected to single- and double
immunolabeling for lectin RCA-1 (Ricinus Communis Agglutinin 1), Iba1 (a
microglial marker), CD68 (specific of macrophages), CD45 (marker for mononucleate
cells of hematopoietic lineage), CD34 (expressed on endothelial cells), and MIB1
and Ki67 (markers for cell proliferation). At 5.5 gw the first intracerebral
microglial cells were seen close to the meninges and choroid plexus near the di
telencephalic fissure. They were amoeboid and positive for Iba1, CD45, and RCA-1,
whereas cells in the deep parenchyma expressed Iba1/CD68/RCA-1 and constituted
clusters. In the developing diencephalon, microglial clusters were located in
junctional regions of the white matter anlagen, most notably at the junctions of
the internal capsule with the thalamic projections, the external capsule, and the
cerebral peduncle. In the cortical anlagen, Iba1+/RCA-1/CD68+/CD45+ cells
accumulated at 10-12 gw, constituting a tangential band at the junction between
the cortical plate and the subplate. Between 10 and 16 gw microglial clusters
increased markedly in size and cellular density. Contact between Iba1+ microglia
and CD34+ blood vessels was clearly visible from 10-12 gw onward, first in
microglial clusters of the white matter anlagen and subsequently throughout the
parenchyma. From the middle of the second trimester onward microglial cells
colonized the entire cerebral parenchyma, developed a ramified morphology, and
downregulated their surface antigens, but remained more numerous in the white
matter.
PMID- 17029272
TI - Hypoperfusion of the visual pathway in parkinsonian patients with visual
hallucinations.
AB - Little is known about the developing mechanisms of visual hallucinations in
Parkinson's disease. This study aimed to investigate perfusion changes in
parkinsonian patients with visual hallucinations using n-isopropyl-p
[123I]iodoamphetamine ([123I]IMP) single photon emission computed tomography
imaging. A total of 70 consecutive patients, including 31 patients with visual
hallucinations, and 39 patients without hallucinations, participated in this
study. Patients with severe cognitive impairment (Mini-Mental State Examination
score < 20), nonvisual hallucinations, or confusion were excluded. We compared
brain perfusion changes between the two groups. We found that hallucinatory
patients had significant perfusion reductions in the bilateral inferior parietal
lobule, inferior temporal gyrus, precuneus gyrus, and occipital cortex compared
to nonhallucinatory patients. These results suggested that hypoperfusion of the
visual pathway was closely related to visual hallucinations in Parkinson's
disease.
PMID- 17029273
TI - Associations between family history of Parkinson's disease and dementia and risk
of dementia in Parkinson's disease: A community-based, longitudinal study.
AB - Dementia is common in patients with Parkinson's disease (PDD). The etiology of
PDD is still unclear, but exciting advances have been made in discovering
pathogenetic components in Parkinson's disease (PD), implicating the role of
genetic factors. It is, however, still controversial whether genetic factors also
contribute to the development of dementia in PD. Thus, we investigated the
association between development of dementia and a positive family history of PD
or dementia in a community-based study of PD in Rogaland County, Norway (n =
219). The patients were followed prospectively with neurological and
neuropsychological assessments. Dementia was more common in patients with a
strong family association of PD (first-degree relatives > second-degree relatives
> no family history; P < 0.05). However, time to dementia did not differ between
the two groups. No associations between dementia in PD and familial occurrence of
dementia could be shown. Further studies with larger samples are needed to
explore a possible relationship between a family history of PD and development of
dementia in PD and its potential pathogenetic mechanisms.
PMID- 17029274
TI - Measures of dyspnea in patients with amyotrophic lateral sclerosis.
AB - Respiratory symptoms are not well characterized in amyotrophic lateral sclerosis
(ALS). The baseline dyspnea index (BDI) and transition dyspnea index (TDI) are
indices designed to measure change in dyspnea over time. They are easy to
administer and do not inquire about specific physical tasks. The latter makes
these scales particularly well suited for use in ALS. This study evaluated the
ability of the BDI and TDI to measure dyspnea in 46 subjects with ALS. The
BDI/TDI had excellent reproducibility. The TDI detected worsening dyspnea by 4
weeks and declined significantly more over the subsequent 8 weeks. The TDI was
significantly associated with changes in forced vital capacity and appeared more
sensitive to changes in dyspnea than the ALS functional rating scale-respiratory
subscale (ALS-FRS R) and a visual analog scale of breathlessness. The BDI and TDI
thus appear to be useful measures in ALS and may have both clinical and research
applications.
PMID- 17029275
TI - Long-term outcome of hematuria home screening for bladder cancer in men.
AB - BACKGROUND: The objectives of this study were to determine whether bladder cancer
(BC) screening in healthy men could lead to earlier detection and reduced BC
mortality compared with unscreened men and to determine long-term outcomes of a
geographically defined, unscreened population with newly diagnosed BC. METHODS:
In 1987 and from 1998 to 1992, 1575 men ages 50 years and older who were
solicited from well patient rosters in clinics in and around Madison, Wisconsin,
tested their urine repetitively with a chemical reagent strip for hemoglobin.
Participants who had positive test results underwent standard urologic
evaluation. BC grades and stages and the outcomes of men with BC detected by
screening were compared with the grades, stages, and outcomes of 87% of men ages
50 years and older with newly diagnosed BC who were reported to the Wisconsin
Tumor Registry in 1988 (n = 509 men). RESULTS: Two hundred fifty-eight screening
participants (16.4%) were evaluated for hematuria, and 21 participants (8.1%)
were diagnosed with BC. Proportions of low-grade (Grade 1 and 2) superficial
(Stage Ta and T1) versus high-grade (Grade 3) superficial or invasive (Stage > or
= T2) cancers in screened men (52.4% vs. 47.7%) and in men from the tumor
registry (60.3% vs. 39.7%) were similar (P = .50). The proportion of high-grade
superficial or invasive BCs that were invasive were lower in screened men (10%)
than in unscreened men (60%; P = .002). At 14 years of follow-up, no men with
screen-detected BC had died of BC, whereas 20.4% of men with unscreened BC had
died of BC (P = .02). CONCLUSIONS: Screening effected the early detection of BC
and may reduce mortality from BC compared with BC that is diagnosed at standard
clinical presentation.
PMID- 17029276
TI - Improved tolerability and quality of life with maintained efficacy using twice
daily low-dose interferon-alpha-2b: results of a randomized phase II trial of low
dose versus intermediate-dose interferon-alpha-2b in patients with metastatic
renal cell carcinoma.
AB - BACKGROUND: In vivo data have shown a more potent antiangiogenic effect and a
higher antitumor activity of low-dose interferon (IFN) given twice daily. In a
randomized Phase II trial, the authors tested the hypothesis that twice-daily low
dose IFN is more effective than daily intermediate-dose IFN in patients with
metastatic renal cell cancer (MRCC). METHODS: A total of 118 patients (59 per
arm) were randomly assigned to receive IFN at a dose of 0.5 million units (MU)
given subcutaneously twice daily (IFN1) or IFN at a dose of 5 MU given
subcutaneously daily (IFN5). The primary endpoint was progression-free survival
(PFS). Secondary endpoints included response rate (RR), overall survival (OS),
toxicity, and quality of life (QOL). RESULTS: There were no significant
differences in either PFS or OS between IFN1 and IFN5 (median of 3.7 months and
median of 3.4 months PFS, respectively; median of 25.5 months and median of 17.5
months OS, respectively). The RRs were identical in the 2 arms (6.7%; 95%
confidence interval [95% CI], 1.8-16.5%). Two patients, 1 in each arm, remained
in complete remission at the time of last follow-up, at 45+ and 38+ months from
treatment. Thirty-two patients receiving IFN5 and 19 patients receiving IFN1
experienced Grade 3 or higher adverse events (graded using the National Cancer
Institute Common Toxicity Criteria [version 2.0]) (P = .025). Eighteen patients
receiving IFN5 and 4 patients receiving IFN1 had dose reductions (P = .002).
There was a significant deterioration in QOL and an increase in depression
associated with IFN5 but no change was noted with IFN1. CONCLUSIONS: Compared
with IFN5, IFN1 is neither more nor less effective but is less toxic, with a
better reported QOL. These results may have implications for the design of
combination regimens incorporating IFN with targeted agents.
PMID- 17029277
TI - Stability, limb coordination and substrate type: the ecorelevance of gait
sequence pattern in primates.
AB - The coordination of limb movements during mammalian locomotion has been well
documented in the literature. Most mammals use lateral sequence (LS) gaits, in
which a forelimb follows an ipsilateral hind limb during the stride cycle.
Primates, however, tend to utilize diagonal sequence (DS) gaits, whereby a
contralateral forelimb follows a given hind limb during the stride cycle. A
number of scenarios have been offered to explain why primates favor DS gaits,
most of them relating to the use of the arboreal habitat and, in particular, the
exploitation of a terminal branch niche. Yet to date, there is surprisingly
little evidence to support the advantage of DS gaits for negotiating different
aspects of the terminal branch environment. Nonetheless, it is apparent that
primates possess unique morphologies and a higher than typically recognized
degree of flexibility in gait sequence pattern, both of which likely offer
advantages for moving upon discontinuous and unstable terminal branches. This
paper reviews potential explanations for the use of DS gaits in primates and
considers mechanisms by which gait sequence may be altered during different types
of arboreal challenges.
PMID- 17029278
TI - Botulinum toxin and neuromotor rehabilitation: An integrated approach to
idiopathic cervical dystonia.
AB - Currently, the best treatment option for idiopathic cervical dystonia (ICD) is
injection of botulinum toxin (BTX) into the affected muscles, whereas
rehabilitative approaches have given disappointing results. We evaluated whether
the association of an ad hoc rehabilitative program may improve the clinical
efficacy of BTX treatment in a single-center, cross-over, controlled study. Forty
patients with ICD were randomly assigned to two different treatment groups: (1)
BTX type A (BTX-A) plus a specific program of physical therapy (BTX-PT) or (2)
BTX-A alone (BTX-0). Patients in the BTX-PT group showed a longer duration of the
clinical benefit (118.8 vs. 99.1 days) and needed a lower dose of BTX at
reinjection (284.5 vs. 325.5 units). In addition, they showed more marked
reductions in their disability in activities of daily living (-9.7 vs. -4.85
points) and subjective pain (-13.35 vs. 6.95 points) scores. Association of BTX-A
therapy with a specific program of physical therapy may improve ICD treatment
outcome.
PMID- 17029279
TI - Cost savings associated with the use of fine-needle aspiration biopsy (FNAB) for
the diagnosis of palpable masses in a community hospital-based FNAB clinic.
AB - BACKGROUND: Generally, it is assumed that fine-needle aspiration biopsy (FNAB)
for the diagnosis of superficial, palpable masses is a less expensive alternative
to diagnostic open surgical biopsy; however, to the authors' knowledge few
studies to date have sought to quantify the number of diagnostic surgical
procedures avoided and cost savings involved. In this article, the authors report
their experience with 664 FNAB procedures that were performed by a
cytopathologist/cytotechnologist team practicing in a community setting. METHODS:
Records from a total of 664 consecutive FNAB cases from 607 patients who
underwent FNAB in a community hospital-based FNAB clinic between 2003 and 2005
were reviewed retrospectively, and follow-up data were obtained. RESULTS: Surgery
was averted entirely as a result of the FNAB in 83% or 505 of 609 cases with
follow-up available. The FNAB procedure was highly accurate and considerably less
expensive than surgical biopsy. CONCLUSION: For patients who presented with
palpable masses, FNAB was a reliable, cost-effective initial method for obtaining
a tissue diagnosis.
PMID- 17029280
TI - Identification of high-grade cervical dysplasia by the detection of p16INK4a in
cell lysates obtained from cervical samples.
AB - BACKGROUND: Current cervical cancer screening approaches are based on cytology
supplemented by human papillomavirus (HPV) testing in some settings. Whereas
cytology is laborious and depends on the cytologists' experience, HPV testing has
limited specificity when it is used to detect high-grade lesions. A dichotomous
test to identify high-grade lesions with greater specificity may be a useful tool
for cervical cancer screening. p16(INK4a) is a cell-cycle regulator that has
demonstrated strong overexpression in cervical precancer cells and cervical
cancer induced by the deregulated expression of HPV oncogenes. METHODS: The
authors used a sandwich enzyme-linked immunosorbent assay (ELISA) to quantify the
amount of solubilized p16(INK4a) protein in lysates that were prepared from
cervical samples to detect high-grade cervical lesions. In total, 187 specimens
that were obtained after sampling for conventional cytology in women who attended
a cervical colposcopy clinic were analyzed. Seventy-six women underwent a biopsy,
and 45 of those women showed histologically confirmed, high-grade cervical
intraepithelial neoplasia. RESULTS: For 76 women with biopsy-proven diagnoses,
receiver operating characteristic (ROC) analysis of different cutoff values
showed an area under the ROC curve of 0.89 for the detection of high-grade
cervical dysplasia. At a cutoff value of 8 U/mL, the sensitivity of the
p16(INK4a) ELISA for detecting high-grade dysplastic cervical lesions was 96%.
CONCLUSIONS: The data obtained in this study suggested that ELISA-based
quantification of solubilized p16(INK4a) protein may have high sensitivity for
detecting cervical precancer. Further population-based studies will be necessary
to analyze the specificity and predictive values of p16(INK4a) protein
quantification in cervical samples.
PMID- 17029281
TI - What are the relations between mechanics, gait parameters, and energetics in
terrestrial locomotion?
AB - Are the different energy-conserving mechanics (i.e., pendulum and spring) used in
different gaits reflected in differences in energetics and/or stride parameters?
The analysis included published data from several species and new data from
horses. When changing from pendulum to spring mechanics, there is a change in the
slope of metabolic rate (MR) vs. speed in all species, in birds and quadrupeds
there is no step increase, and in humans there are conflicting reports. At the
trot-gallop transition, where quadrupeds are hypothesized to change from spring
mechanics to some combination of spring and pendulum mechanics, there is a change
in slope of MR vs. speed in horses but not in other species. Stride frequency
(SF) is a logarithmic function of walking speed in all species, a linear function
of trotting/running speed, and nearly independent of speed in galloping. In
humans and horses there is a discontinuity in SF at the walk-trot (run)
transition but not in birds. The slope of time of contact vs. speed does not
change with mechanics in most species, but it does in humans. In horses and
humans, there is a discontinuity at the walk-trot (run) transition and data for
other species do not permit generalization. Duty factor (DF) in humans is greater
than 0.5 in walking (pendulum mechanics) and less than 0.5 when running (spring
mechanics). However, this is not true in many species that have DF>0.5 at the
lowest speeds where they use spring mechanics. When trotting at low speeds,
horses use forelimb DF>0.5 and hind limb DF<0.5. Thus, it is confusing to
distinguish between walking and running by DF.
PMID- 17029282
TI - De novo nonalcoholic fatty liver disease after liver transplantation.
AB - Hepatic steatosis is a recognized problem in patients after orthotopic liver
transplant (OLT). However, de novo development of nonalcoholic fatty liver
disease (NAFLD) has not been well described. The aim of this study was to
determine the prevalence and predictors of de novo NAFLD after OLT. A
retrospective analysis was performed on 68 OLT patients with donor liver biopsies
and posttransplantation liver biopsies. Individual medical charts were reviewed
for demographics, indication for OLT, serial histology reports, genotypes for
hepatitis C, comorbid conditions, and medications. Liver biopsies were reviewed
blindly and graded according to the Brunt Scoring System. Multivariate logistic
regression analysis was used to study the risk factors for developing NAFLD. The
interval time from OLT to subsequent follow-up liver biopsy was 28 +/- 18 months.
A total of 12 patients (18%) developed de novo NAFLD, and 6 (9%) developed de
novo NASH. The regression model indicated that the use of angiotensin-converting
enzyme inhibitors (ACE-I) was associated with a reduced risk of developing NAFLD
after OLT (odds ratio, 0.09; 95% confidence interval, 0.010-0.92; P = 0.042).
Increase in body mass index (BMI) of greater than 10% after OLT was associated
with a higher risk of developing NAFLD (odds ratio, 19.38; 95% confidence
interval, 3.50-107.40; P = 0.001). In conclusion, de novo NAFLD is common in the
post-OLT setting, with a significant association with weight gain after
transplant. The use of an ACE-I may reduce the risk of developing post-OLT NAFLD.
PMID- 17029283
TI - Use of split-liver allografts does not impair pediatric recipient growth.
AB - The use of split-liver (SL) allografts continues to be an excellent option for
many pediatric recipients. Patient and graft survival with this graft type are
comparable to patient and graft survival with whole organ grafts. Quality-of-life
issues, specifically growth, for SL recipients have not been compared to those of
recipients of more conventional whole-organ recipients. Pediatric recipients of
SL and whole allografts at 2 institutions were identified. Height, z score, and
delta z score were calculated for all recipients for each year after transplant.
Between 1995 and 2004, 201 pediatric liver transplants were analyzed. Data were
collected on 39 split-graft recipients and 36 whole-size recipients. Only
subjects 3 years or younger were included in the study. Growth retardation was
present in all recipients at transplant. Height z score post split and whole-size
transplant were not statistically different at 1- (P = 0.65), 2- (P = 0.13), and
3-year (P = 0.32) anniversaries, respectively. Catch-up growth was present only
in recipients of split grafts. In conclusion, the use of split grafts as opposed
to whole-size grafts revealed no significant differences in terms of linear
growth. Our report indicates that split-liver transplantation does not impair
recipient growth.
PMID- 17029284
TI - Transthyretin-derived amyloid deposition on the gastric mucosa in domino
recipients of familial amyloid polyneuropathy liver.
AB - Familial amyloid polyneuropathy (FAP) is a form of hereditary generalized
amyloidosis. Liver tissue explanted from FAP patients has normal structure and
function, except for the production of amyloidogenic variant transthyretin (TTR),
and domino liver transplantation (DLT) using grafts from FAP patients was first
performed in 1995. FAP symptoms usually develop in genetically determined
individuals after the age of 20, but it is difficult to estimate when FAP
symptoms will appear in domino recipients. Concerning this problem, histological
findings showing amyloid deposition have recently been obtained in a few domino
recipients of FAP livers. This study investigated the presence of de novo amyloid
deposition in the gastroduodenal mucosa of domino recipients transplanted at our
institution. Biopsy of gastroduodenal mucosa was carried out in 5 recipients of
FAP livers and TTR-derived amyloid deposits were detected in 2 patients, both of
whom had undergone DLT 47 months previously. In FAP liver recipients, de novo
systemic amyloid deposition may begin much sooner than previously supposed.
Therefore, careful follow-up of domino recipients of FAP livers is required.
PMID- 17029285
TI - Satellite cells express distinct patterns of myogenic proteins in immature
skeletal muscle.
AB - Satellite cells are the myogenic cells lying between the myofiber sarcolemma and
basal lamina. The objective of this study was to determine the expression
patterns of MyoD, myogenin, and Pax7 within the satellite cell population in the
growing rat soleus and extensor digitorum longus (EDL) muscles. Secondly, the
expression of the myogenic markers was also studied within the interstitial cell
compartment and myonuclei. It was discovered that the soleus contained a higher
number of Pax7, MyoD, or myogenin-positive nuclei compared with the EDL.
Similarly, myogenin was expressed at a lower level in the myonuclei of the soleus
compared with the EDL, and myogenin was expressed at a higher level in the
interstitial compartment of the soleus compared with the EDL. When interstitial
nuclei, myonuclei, and double-labeled nuclei were used in the estimate of the
satellite cell population, it was discovered that approximately of 13% of the
myofibers in a transverse section of the soleus muscle and 4.1% of EDL myofibers
exhibit a labeled satellite cell nucleus. Overall, results from this study
suggest that expression patterns of these markers vary predictably among muscles
with different growth dynamics and phenotypic characteristics.
PMID- 17029286
TI - Neural stem cells for the treatment of disorders of the enteric nervous system:
strategies and challenges.
AB - The main goal of this review is to summarize the status of the research in the
field of stem cells transplantation, as it is applicable to the treatment of
gastrointestinal motility. This field of research has advanced tremendously in
the past 10 years, and recent data produced in our laboratories as well as others
is contributing to the excitement on the use of neural stem cells (NSC) as a
valuable therapeutic approach for disorders of the enteric nervous system
characterized by a loss of critical neuronal subpopulations. There are several
sources of NSC, and here we describe therapeutic strategies for NSC
transplantation in the gut. These include using NSC as a relatively nonspecific
cellular replacement strategy in conditions where large populations of neurons or
their subsets are missing or destroyed. As with many other recent "breakthroughs"
stem cell therapy may eventually prove to be overrated. However, at the present
time, it does appear to provide the hope for a true cure for many currently
intractable diseases of both the central and the peripheral nervous system.
Certainly more extensive research is needed in this field. We hope that our
review will encourage new investigators in entering this field of research ad
contribute to our knowledge of the potentials of NSC and other cells for the
treatment of gastrointestinal dysmotility.
PMID- 17029287
TI - Mes2, a MADF-containing transcription factor essential for Drosophila
development.
AB - The development of the Drosophila mesoderm is initiated by the basic helix-loop
helix transcription factor twist. We identified a gene encoding a putative
transcription factor, mes2, in a screen for essential mesoderm-expressed genes
that function downstream of twist. Mes2 protein belongs to a family of 48
Drosophila proteins containing MADF domains. MADF domains exist in worms, flies,
and fish. Mes2 is a nuclear protein first produced in trunk and head mesoderm
during late gastrulation. At later embryonic stages, mes2 is expressed in glia of
the central and peripheral nervous systems, and in tissues derived from the head
mesoderm. We have identified a null mutation of mes2 that leads to developmental
arrest in first instar larvae. Increased production of Mes2 in multiple embryonic
and larval tissues almost always causes lethality. The ubiquitous or epidermal
misexpression of mes2 in the embryo causes a dramatic loss of epidermal integrity
resulting in the failure of dorsal closure. Our data show that the precise
regulation of mes2 expression is critical for normal development in Drosophila
and implicate Mes2 in the regulation of essential target genes.
PMID- 17029288
TI - Two-dimensional morphogen gradient in Xenopus: boundary formation and real-time
transduction response.
AB - Morphogen gradients play an important role in pattern formation in embryo.
However, the interpretation of position in a morphogen gradient is not well
understood. Because it is hard to analyze morphogen gradients especially in
opaque embryos such as those of Xenopus, it is necessary to fix and section the
embryo, thereby eliminating the possibility of real-time observation, and making
more difficult the interpretation of events that take place in three dimensions.
We describe here a two-dimensional preparation of cells from a Xenopus blastula
animal cap, in which an activin concentration gradient appears to be formed and
interpreted at the same rate and in the same way as in normal embryos. We use two
dimensional preparations of this kind to contribute the following new information
about gradient formation and interpretation in embryo. We determine the dynamics
of formation of an activin activity gradient in real time. We demonstrate that
this gradient is established by diffusion of activin through intercellular space
and does not require internalization of receptor or ligand. We also show that the
generation of a boundary of gene expression depends on the interpretation, rather
than a change of composition, of the concentration gradient.
PMID- 17029289
TI - Trends of selected malformations in relation to folic acid recommendations and
fortification: an international assessment.
AB - BACKGROUND: Two crucial issues relative to the benefits and impact of folic acid
in the prevention of birth defects are whether supplementation recommendations
alone, without fortification, are effective in reducing the population-wide rates
of neural tube defects (NTDs), and whether such policies can reduce the
occurrence of other birth defects. Using data from 15 registries, we assessed
rates and trends of 14 major defects, including NTDs, in areas with official
recommendations or fortification to assess the effectiveness of recommendations
and fortification on a wide range of major birth defects. METHODS: We evaluated
surveillance data through 2003 on major birth defects from population-based
registries from Europe, North America, and Australia. All included ascertainment
of pregnancy terminations (where legal). Trends before and after policies or
fortification were assessed via Poisson regression and were compared via rate
ratios. RESULTS: Significant changes in trends were seen for NTDs in areas with
fortification but not in areas with supplementation recommendations alone. For
other major birth defects, there was an overall lack of major trend changes after
recommendations or fortification. However, some significant declines were
observed for select birth defects in individual areas. CONCLUSIONS:
Recommendations alone remain an ineffective approach in translating the known
protective effect of folic acid in population-wide decline in NTD rates.
Fortification appears to be effective in reducing NTDs. The effect on other birth
defects remains unclear.
PMID- 17029290
TI - The M3/M4 cytoplasmic loop of the alpha1 subunit restricts GABAARs lateral
mobility: a study using fluorescence recovery after photobleaching.
AB - A crucial problem in neurobiology is how neurons are able to maintain
neurotransmitter receptors at specific membrane domains. The large structural
heterogeneity of gamma aminobutyric acid receptors (GABAARs) led to the
hypothesis that there could be a link between GABAAR gene diversity and the
targeting properties of the receptor complex. Previous studies using Fluorescence
Recovery After Photobleaching (FRAP) have shown a restricted mobility in GABAARs
containing the alpha1 subunit. The M3/M4 cytoplasmic loop is the region of the
alpha1 subunit with the lowest sequence homology to other subunits. Therefore, we
asked whether the M3/M4 loop is involved in cytoskeletal anchoring and GABAAR
clustering. A series of alpha1 chimeric subunits was constructed: alpha1CH
(control subunit), alpha1CD (Cytoplasmic loop deleted), alpha1CD2, and alpha1CD3
(alpha1 with the M3/M4 loop from the alpha2 and alpha3 subunits, respectively).
Our results using FRAP indicate an involvement of the M3/M4 cytoplasmic loop of
the alpha1 subunit in controlling receptor lateral mobility. On the other hand,
inmunocytochemical approaches showed that this domain is not involved in subunit
targeting to the cell surface, subunit-subunit assembly, or receptor aggregation.
PMID- 17029291
TI - Myosin16b: The COOH-tail region directs localization to the nucleus and
overexpression delays S-phase progression.
AB - Rat Myo16a and Myo16b comprise the founding members of class XVI myosin and are
characterized by an N-terminal ankyrin repeat domain thought to mediate an
association with protein phosphatase 1 catalytic subunits 1alpha and 1gamma.
Myo16b is the principal isoform and reveals predominant expression in developing
neural tissue. Here, we use COS-7 cells as a model system to develop an
understanding of Myo16b function. We find that Myo16b displays predominant
localization in the nucleus of cells transitioning through interphase, but is not
associated with processes of mitosis. Using a panel of EGFP-Myo16b-expression
plasmids in transient transfection studies, we identified the COOH-terminal
residues 1616-1912 as necessary and solely sufficient to target Myo16b to the
nucleus. We show that the Myo16b-tail region directs localization to a nuclear
compartment containing profilin and polymerized actin, which appears to form a
three-dimensional meshwork through the depth of the nucleus. Further, we
demonstrate that this compartment localizes within euchromatic regions of the
genome and contains proliferating cell nuclear antigen (PCNA) and cyclin A, both
markers of S-phase of the cell cycle. Cells transiently expressing Myo16b or
Myo16b-tail region show limited incorporation of BrdU, delayed progression
through S-phase of the cell cycle, and curtailed cellular proliferation.
PMID- 17029292
TI - Macrophages promote collagen fibrillogenesis around terminal end buds of the
developing mammary gland.
AB - Development of the ductal network in the mammary gland is dependent in part on
the presence of macrophages. Here we utilize multi-photon microscopy and second
harmonic generation to describe terminal end bud 3-dimensional structure and the
organization of the surrounding collagen matrix. We have applied this approach to
analyze the effect of macrophage deficiency on terminal end bud structure and
collagen organization, using mice homozygous for a null mutation in the colony
stimulating factor-1 gene (Csf1op/Csf1op). Primary terminal end buds have an
oblong shape, with long collagen I fibers close to the neck of the terminal end
bud and radiating upwards in the direction of growth. Around the terminal end
buds, the amount of total collagen I detected by antibody staining was not
affected by macrophage deficiency. However the amount of collagen I organized
into long fibers, detected by second harmonic generation signal, was reduced in
Csf1op/Csf1op mice. Macrophage deficiency also caused terminal end buds to be
rounder and shorter. These studies reveal a role for macrophages in collagen
fibrillogenesis and in organization of the structure of terminal end buds.
PMID- 17029293
TI - Expression of connexins 36, 43, and 45 during postnatal development of the mouse
retina.
AB - Gap junction channels formed by connexins (Cx) may play essential roles in some
processes that occur during retinal development, such as apoptosis and calcium
wave spread. The present study was undertaken to determine the distribution
pattern of Cx36, Cx43, and Cx45 by immunofluorescence, as well as their gene
expression levels by quantitative PCR during postnatal development of the mouse
retina. Our results showed an increased expression of neuronal Cx36 from P1 until
P10, when this Cx reached adult levels, and it was mainly distributed in the
outer and inner plexiform layers. In turn, Cx43 was almost absent in retinal
progenitor cells at P1, it became more prominent in glial cell processes about
P10, and did not change until adulthood. Double-labeling studies in situ and in
vitro with antivimentin, a Muller cell marker, confirmed that Cx43 was expressed
by these cells. In addition, quantitative PCR showed that Cx43 and vimentin
shared very similar temporal expression patterns. Finally, in contrast to Cx36
and Cx43, Cx45 mRNA was strongly down-regulated during development. In early
postnatal days, Cx45 was seen ubiquitously distributed throughout the retina in
cells undergoing proliferation and differentiation, as well in differentiated
neurons. In adult retina, this protein had a more restricted distribution both in
neurons and glial cells, as confirmed in situ and in vitro. In conclusion, we
observed a distinct temporal expression pattern for Cx36, Cx43, and Cx45, which
is probably related to particular roles in retinal function and maintenance of
homeostasis during development of the mouse retina.
PMID- 17029294
TI - ColVa1 and ColXIa1 are required for myocardial morphogenesis and heart valve
development.
AB - Genetic mutations in minor fibrillar collagen types Va1 (ColVa1) and XIa1 (ColXI)
have been identified in connective tissue disorders including Ehlers-Danlos
syndrome and chondrodysplasias. ColVa1+/- and ColXIa1-/- mutant mice recapitulate
these human disorders and show aberrations in collagen fiber organization in
connective tissue of the skin, cornea, cartilage, and tendon. In the heart,
fibrous networks of collagen fibers form throughout the ventricular myocardium
and heart valves, and alterations in collagen fiber homeostasis are apparent in
many forms of cardiac disease associated with myocardial dysfunction and valvular
insufficiency. There is increasing evidence for cardiac dysfunction in connective
tissue disorders, but the mechanisms have not been addressed. ColVa1+/- and
ColXIa1-/- mutant mice were used to identify roles for ColVa1 and ColXIa1 in
ventricular myocardial morphogenesis and heart valve development. These affected
cardiac structures show a compensatory increase in type I collagen deposition,
similar to that previously described in valvular and cardiomyopathic disease.
Morphological cardiac defects associated with changes in collagen fiber
homeostasis identified in ColVa1+/- and ColXIa1-/- mice provide an insight into
previously unappreciated forms of cardiac dysfunction associated with connective
tissue disorders.
PMID- 17029295
TI - The production of (R)-2-hydroxy-1-phenyl-propan-1-one derivatives by benzaldehyde
lyase from Pseudomonas fluorescens in a continuously operated membrane reactor.
AB - Benzaldehyde lyase (BAL; E.C. 4.1.2.38) from Pseudomonas fluorescens Biovar I
catalyzes the reversible formation of benzoins from aromatic aldehydes, and,
moreover, the coupling of aromatic with aliphatic aldehydes yielding derivatives
of (R)-2-hydroxy-1-phenyl- propan-1-one (R)-HPPs), which are important chiral
building blocks. In this paper, we report on the development of a reactor system
that allows the selective production of substituted (R)-HPP-derivatives. The
reaction systems yielding (R)-1-(3-chloro-phenyl)-2-hydroxy- propan-1-one, (R)-2
hydroxy-3-methoxy-1-(4-methoxy-phenyl)-propan-1-one, and (R)-2-hydroxy-3,3
dimethoxy-1-phenyl-propan-1-one were investigated. A kinetic model optimized by
batch experiments was developed, for the description of both batch and
continuously operated reactors. This model was used to describe the HPP
production in a continuously operated enzyme membrane reactor. The reactor type
used combines the advantages of high conversion and excellent selectivity with
high space-time yields and total turnover numbers of up to ttn=43,000. Products
were obtained in high yield on a gram scale.
PMID- 17029296
TI - Interaction of polyamine gene vectors with RNA leads to the dissociation of
plasmid DNA-carrier complexes.
AB - BACKGROUND: Plasmid DNA (pDNA) dissociation from polyamine gene vectors after
cellular uptake has not been well characterized. A more detailed understanding of
this process could lead to more efficient gene transfer agents. Since RNA is
present in the cytoplasm at high concentrations and due to its structural
similarity to DNA, we were interested in its conceivable interaction with
polyamine gene vectors. METHODS: In a first set of experiments gene vectors were
incubated in cell lysate and pDNA release was investigated by Southern blot
analysis with or without RNase A pretreatment and by confocal laser scanning
microscopy. Further, interaction of polyamine gene vectors with RNA was
investigated by fluorescence quenching assay. These methods were complemented by
a functionality assay using isolated nuclei. RESULTS: The incubation of gene
vectors with cell lysate resulted in the dissociation of pDNA from the complexes.
This effect was abolished when the cell lysate was pretreated with RNase A. The
addition of RNA in the absence of cell lysate led also to a dissociation of pDNA.
This process commenced instantaneously after the addition of RNA as analyzed by
fluorescence quenching. When gene vectors were incubated in cell lysate
containing isolated nuclei, the dissociation of pDNA from the polyamine gene
vectors occurred preferentially extranuclearally as confirmed by confocal laser
scanning microscopy. These results were further corroborated in a functional
assay. CONCLUSIONS: These data suggest that RNA induces pDNA dissociation from
the polyamine gene vectors. Furthermore, this process apparently occurs in the
cytoplasm before the gene vectors enter the nucleus.
PMID- 17029297
TI - Novel mutations in prenatal diagnosis of primary microcephaly.
PMID- 17029298
TI - CT ratios: parameter estimates are inconsistent with SURUSS publications?
PMID- 17029299
TI - Second-trimester intra-abdominal bowel dilation in fetuses with gastroschisis
predicts neonatal bowel atresia.
AB - OBJECTIVE: To determine in fetuses with gastroschisis the association between
intra-abdominal bowel dilation in the second trimester and neonatal bowel
atresia. METHODS: We reviewed ultrasound and medical records of fetuses with
gastroschisis from January 1998 to August 2004. Fetuses with intra-abdominal
bowel dilation in the second trimester were identified and followed into the
neonatal period. RESULTS: We identified 58 mother-infant pairs showing fetal
gastroschisis, with at least one prenatal ultrasound at our hospital and which
were delivered there, or were transported there as newborns. Forty-eight of the
58 fetuses had no intra-abdominal bowel dilation and none of these neonates had
bowel atresia. Ten of the 58 fetuses had intra-abdominal bowel dilation and all
had bowel atresia at birth (P<0.0001). In eight cases in which ultrasound was
performed at <25 weeks' gestation, intra-abdominal bowel dilation was already
present. CONCLUSION: Intra-abdominal bowel dilation in the second trimester
predicts neonatal bowel atresia in fetuses with gastroschisis.
PMID- 17029300
TI - Prenatal diagnosis of X chromosome monosomy.
PMID- 17029302
TI - Commercial kit-based diagnosis is not enough for prenatal testing of beta
thalassemia: pitfalls in diagnostic mutation analysis raises the need for
reference laboratories.
PMID- 17029303
TI - Effect of antipsychotic replacement with quetiapine on the symptoms and quality
of life of schizophrenic patients with extrapyramidal symptoms.
AB - Replacement of antipsychotic drugs with quetiapine (QTP) was tried in a
naturalistic setting in chronic schizophrenic patients who still showed moderate
psychiatric symptoms and either showed extrapyramidal symptoms (EPS) or took anti
parkinson drugs for the EPS. QTP was added on and gradually increased while the
previous drugs were tapered and discontinued whenever possible. Clinical
symptoms, objective and subjective QOL, and EPS were measured before and 6 months
after QTP addition, using Brief Psychiatric Rating Scale (BPRS), Quality of Life
Scale (QLS), Schizophrenia Quality of Life Scale (SQLS) and Drug-Induced
Extrapyramidal Symptom Scale (DIEPSS), respectively. Twenty-one patients
completed the trial and received the assessment. It was found that replacement
with QTP-improved clinical symptoms, objective and subjective QOL and EPS. This
improvement was equally observed in not only patients who switched to QTP
monotherapy (n = 11) but also patients who took QTP together with reduced small
doses (4.4 +/- 4.3 mg/day) of previous drugs (n = 11). The results suggest that
replacement with QTP improves symptoms as well as objective and subjective QOL in
a subgroup of schizophrenia.
PMID- 17029304
TI - Is the loudness dependence of auditory evoked potentials modulated by the
selective serotonin reuptake inhibitor citalopram in healthy subjects?
AB - The loudness dependence of auditory evoked potentials (LDAEP) has been discussed
as a non-invasive in vivo marker of central serotonergic function. Evidence for
this has been found in animal studies, but studies in humans provide less
consistent results. In this study, the relationship between LDAEP and directly
modulated central serotonergic activity in healthy subjects was investigated. In
a single-blind cross-over design, the LDAEP of female participants (age: 24.0 +/-
2.3 years) was measured under two conditions: (1) infusion of 20 mg citalopram
diluted in 250 ml 0.9% saline and (2) infusion of 250 ml 0.9% saline as placebo.
LDAEP was measured at five different time points before, during and up to 60 min
after drug/placebo administration and dipole source analysis was performed. The
increase of the central serotonin activity in response to citalopram was not
accompanied by a significant change of the LDAEP compared to the placebo
condition. The result underlines that the acceptance of LDAEP as a marker of
central serotonergic function still needs further discussion.
PMID- 17029305
TI - Effect of risperidone on plasma catecholamine metabolites and brain-derived
neurotrophic factor in patients with bipolar disorders.
AB - A combination treatment with a mood stabilizer and an antipsychotic drug is often
used in as many as 90% of subjects with acute mania. Recently, augmentation
therapy with atypical antipsychotics has been investigated in both the acute and
long-term treatment of bipolar disorder with or without psychosis. In the present
study, the authors investigated the efficacy of risperidone treatment for both
acute manic and depressive episodes in bipolar disorder. Eighteen patients (M/F:
8/10, age: 34 +/- 15 yr) who met the DSM-IV criteria for bipolar I disorder (12
cases of manic episodes, 6 cases of depressive episodes) with risperidone
treatment were evaluated regarding their clinical improvement using the Young
Mania rating Scale (YMRS) and the Hamilton rating Scale for Depression (Ham-D).
Plasma concentrations of HVA and MHPG were analyzed by HPLC-ECD and plasma brain
derived neurotrophic factor (BDNF) levels were detected by sandwich ELISA. The
mean scores of the YMRS were 22, 18, 12, 8, and 5 at time points before and 1, 2,
3, and 4 weeks after the risperidone administration, respectively. The mean
scores of the Ham-D were 24, 25, 21, 21, and 19 at time points before and 1, 2,
3, and 4 weeks after the risperidone administration, respectively. The plasma
levels of HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed to have
decreased 4 weeks after risperidone administration in manic patients. The levels
did not change in depressive patients. The plasma levels of BDNF were decreased
in depressive patients compared with manic patients or healthy controls. However,
the administration of risperidone did not alter plasma BDNF levels.
PMID- 17029306
TI - A case series of patients with Tourette's syndrome in the United Kingdom treated
with aripiprazole.
AB - OBJECTIVE: These cases illustrate that a new neuroleptic, aripiprazole, may be an
effective treatment for the motor and vocal tics of Tourette Syndrome (TS), even
in younger people. METHOD: A case series of 11 consecutive patients with TS (age
range 7-50 years; M = 7) who were felt to require neuroleptic medication, were
treated with aripiprazole, the majority of whom had been refractory to treatment
with other neuroleptics, and in one case, Habit Reversal Training as well.
RESULTS: Ten out of the 11 patients who were treated with aripiprazole improved,
although to differing degrees. The only individual who showed no response was
treated for only 1 month with a low dose (5 mg). Eight of the patients had been
treated with many typical and atypical neuroleptics without success, and which
had also given unacceptable side effects, resulting in them being unable to
function at times. One was also unresponsive to previous Habit Reversal Training.
The response to aripiprazole was dramatic and quick in five patients; in the rest
(5/10) the response was less dramatic. In the majority of patients, response was
sustained. The successful aripiprazole doses were between 10-20 mg daily. Side
effects were mild and transient. This, to the best of our knowledge, is the first
case series of patients with TS successfully treated with aripiprazole in the
United Kingdom, and one of the few to date in the English Scientific literature.
Our patients are also the first cases reported, in which the patients were
assessed and whose improvement was monitored using standardised schedules and
rating scales, such as the Yale Global Tic Severity Rating Scale and MOVES.
Aripiprazole was licensed for use in patients with schizophrenia in the European
Union in June 2004. We discuss possible reasons for these dramatic and
idiosyncratic responses to aripiprazole. CONCLUSION: We suggest that aripiprazole
may well be useful for individuals with TS as response to it is often quick,
dramatic, sustained and with few generally mild and transient side effects.
PMID- 17029308
TI - Fetal middle cerebral to uterine artery pulsatility index ratios in normal and
pre-eclamptic pregnancies.
AB - OBJECTIVES: To calculate the normal range for the fetal middle cerebral artery
(MCA)/uterine artery pulsatility index (PI) ratio in the third trimester of
pregnancy and to assess its value, compared with that of the MCA/umbilical artery
PI ratio, in predicting an unfavorable outcome of pregnancies complicated by pre
eclampsia. METHODS: Doppler blood flow velocimetry of the uterine and umbilical
arteries and fetal MCA was performed. We calculated the ratios between 1) the PI
of the MCA and the mean PI value of both uterine arteries and 2) the PI of the
MCA and the PI of the umbilical artery. All women were examined at or beyond 26
weeks of gestation. A cross-sectional study of 231 normal pregnancies was
conducted to construct the reference range. Values below the 5th percentile or an
MCA/umbilical artery PI ratio lower than 1.08 were defined as brain-sparing. A
further 115 pregnancies with pre-eclampsia (50 mild and 65 severe) were assessed
prospectively and the results were related to perinatal outcome. The accuracy of
MCA/uterine artery and MCA/umbilical artery PI ratios for prediction of
unfavorable pregnancy outcome was compared. RESULTS: Normal MCA/uterine artery PI
ratios decreased with advancing gestational age. Redistribution of the fetal
circulation indicated by a low MCA/uterine artery PI ratio was seen in 30% of the
mild (n=15) and 46% of the severe (n=30) pre-eclamptic cases. There was a
significant difference between those without and those with signs of brain
sparing, respectively, in mean birth weight (2456.0 vs. 1424.5 g), gestational
age at delivery (35.6 vs. 31.3 weeks) and gestational age at the time of
examination (34.9 vs. 30.9 weeks). Furthermore, there was a significantly higher
rate of small-for-gestational-age (SGA) neonates (57.8% vs. 25.7%), preterm
delivery (100% vs. 81.8%) and Cesarean section (90.7% vs. 66.7%) in cases with an
MCA/uterine artery PI ratio below the 5th percentile. However, there was no
difference between the groups in the rate of low 5-min Apgar scores, admission to
the neonatal intensive care unit, or deliveries before 34 weeks. The MCA/uterine
artery and MCA/umbilical artery PI ratios were similar in the prediction of
adverse perinatal outcome. Both ratios were better at predicting the outcome of
pregnancy than were signs of increased vascular impedance in either the umbilical
or uterine arteries. CONCLUSIONS: Normal MCA/uterine artery PI ratio decreases
with gestational age. Abnormally low MCA/ uterine artery PI ratios are related to
unfavorable pregnancy outcome. The predictive value of the MCA/uterine artery PI
ratio is similar to that of the MCA/umbilical artery PI ratio.
PMID- 17029307
TI - Verbal memory performance during subchronic challenge with a selective
serotonergic and a mixed action antidepressant.
AB - OBJECTIVES: Effects of escitalopram 10-20 mg/day and mirtazapine 30-45 mg/day on
verbal memory of 18 healthy participants were assessed in a randomized, double
blind, placebo-controlled, three-way crossover trial. METHOD: Each treatment
period lasted for 15 days and was separated from the next period by a washout
period of at least 13 days. Participants received an evening dose of escitalopram
10 mg, mirtazapine 30 mg, or placebo from days 1 to 7 and an evening dose of
escitalopram 20 mg, mirtazapine 45 mg, or placebo from days 8 to 15. On days 2,
9, and 16 a visual verbal memory task was performed measuring drug effects during
the acute phase, after dose increase and at steady state. RESULTS: Escitalopram
did not affect immediate or delayed verbal memory score throughout treatment.
During mirtazapine treatment, participants performed less well in the overall
immediate recall score compared to placebo. This impairment was most pronounced
in the final trial of the visual verbal learning task. CONCLUSION: Verbal memory
was not affected by acute and subchronic escitalopram treatment in healthy
participants. Overall immediate verbal memory was slightly but significantly
impaired throughout mirtazapine treatment, probably due to a general reduction in
overall arousal caused by H1 blockade.
PMID- 17029309
TI - Increased enantioselectivity and remarkable acceleration of lipase-catalyzed
transesterification by using an imidazolium PEG-alkyl sulfate ionic liquid.
AB - Several types of imidazolium salt ionic liquids were prepared derived from
poly(oxyethylene)alkyl sulfate and used as an additive or coating material for
lipase-catalyzed transesterification in an organic solvent. A remarkably
increased enantioselectivity was obtained when the salt was added at 3-10 mol %
versus substrate in the Burkholderia cepacia lipase (lipase PS-C)-catalyzed
transesterification of 1-phenylethanol by using vinyl acetate in diisopropyl
ether or a hexane solvent system. In particular, a remarkable acceleration was
accomplished by the ionic liquid coating with lipase PS in an iPr(2)O solvent
system while maintaining excellent enantioselectivity; it reached approximately
500- to 1000-fold acceleration for some substrates with excellent
enantioselectivity. A similar acceleration was also observed for IL 1-coated
Candida rugosa lipase. MALDI-TOF mass spectrometry experiments of the ionic
liquid-coated lipase PS suggest that ionic liquid binds with lipase protein.
PMID- 17029310
TI - A manganese(III) complex that exhibits spin crossover triggered by geometric
tuning.
PMID- 17029311
TI - Activity-stability parameterization of homogeneous green oxidation catalysts.
AB - Small-molecule synthetic homogeneous-oxidation catalysts are normally poorly
protected from self-destruction under operating conditions. Achieving design
control over both activity and half-life is important not only in advancing the
utility of oxidation catalysts, but also in minimizing hazards associated with
their use and disposal. Iron(III)-TAML (tetraamido-macrocyclic ligand) oxidant
catalysts rapidly activate H(2)O(2) for numerous significant processes,
exhibiting high and differing activity and varying half-lives depending upon the
TAML design. A general approach is presented that allows for the simultaneous
determination of the second-order rate constant for the oxidation of a targeted
substrate by the active catalyst (k(II)) and the rate constant for the
intramolecular self-inactivation of the active catalyst (k(i)). The approach is
valid if the formation of the active catalyst from its resting state and the
primary oxidizing agent, measured by the second-order rate constant k(I), is fast
and the catalyst concentration is very low, such that bimolecular inactivation
pathways can be neglected. If the oxidation process is monitored
spectrophotometrically and is set up to be incomplete, the kinetic trace can be
analyzed by using the equation ln(lnA(t))/A(infnity)=ln(k(II)/k(i)[Fe(III)](tot)
k(i)t, from which k(II) and k(i) can be determined. Here, A(t) and A(infinity)
are absorbances at time t and at the end of reaction (t=infinity), respectively,
and [Fe(III)](tot) is the total catalyst concentration. Several tools were
applied to examine the validity of the approach by using a variety of different
Fe(III)-TAML catalysts, H(2)O(2) and tBuOOH as oxidizing agents, and the dyes
safranine O and orange II as target substrates. Learning how catalyst activities
(k(II)) and catalyst half-lives (k(i)) can be controlled by ligand design is an
important step in creating green catalysts that will not persist in the
environment after they have achieved their purpose.
PMID- 17029312
TI - Memory effect of activated Mg-Al hydrotalcite: in situ XRD studies during
decomposition and gas-phase reconstruction.
AB - The thermal decomposition of Mg-Al hydrotalcite and the subsequent reconstruction
of the decomposed products in the presence of water vapor (2 vol. % H(2)O in
N(2)) have been investigated by in situ XRD. Thermographic analysis and
temperature-programmed desorption MS results complemented the diffraction data.
Valuable mechanistic and kinetic insights into these processes, which are of
prime importance for optimal activation of this type of material for catalytic
applications, were obtained. Hydrotalcite decomposition to the mixed oxide
proceeds via formation at 423-473 K of an intermediate phase, consisting of a
highly disordered, dehydrated, layered structure. The latter evolves by removal
of interlayer water on heating, causing a shrinking of the interlayer space (it
is up to 45 % smaller than in the as-synthesized hydrotalcite). Above 623 K,
Mg(Al)O(x) oxide with the periclase structure is formed. Reversion of the
intermediate dehydrated structure to hydrotalcite upon contact with water vapor
is complete and very fast at room temperature. Recovery of hydrotalcite from the
oxide calcined at 723 K is two orders of magnitude slower than rehydration of the
intermediate layered structure and one order of magnitude slower than the
typically practiced liquid-phase reconstruction. In contrast to the
decomposition, the reconstruction mechanism does not involve an intermediate
phase. The gas-phase rehydration and reconstruction was interrupted above 303 K.
This is attributed to the poor wetting of the surface of the decomposed materials
induced by hampered H(2)O adsorption above room temperature at the water vapor
pressure applied. The Avrami-Erofe'ev model describes the reconstruction kinetics
well.
PMID- 17029313
TI - O-O bond formation in the S(4) state of the oxygen-evolving complex in
photosystem II.
AB - Based on recent X-ray structures of the oxygen-evolving complex in photosystem
II, quantum chemical geometry optimizations of several thousand structures have
been performed in order to elucidate the mechanism for dioxygen formation. Many
of the results of these calculations have been presented previously. The
energetically most stable structure of the S(4) state has been used in the
present study to investigate essentially all the possible ways the O--O bond can
be formed in this structure. A key feature, emphasized previously, of the S(4)
state is that an oxygen radical ligand is present rather than an Mn(V) state.
Previous studies have indicated that this oxygen radical can form an O--O bond by
an attack from a water molecule in the second coordination shell. The present
systematic investigation has led to a new type of mechanism that is significantly
favored over the previous one. A calculated transition-state barrier of 12.5 kcal
mol(-1) was found for this mechanism, whereas the best previous results gave 18
20 kcal mol(-1). A requirement on the spin alignment for a low barrier is
formulated.
PMID- 17029314
TI - Bridging rotaxanes' wheels--cyclochiral bonnanes.
PMID- 17029315
TI - Tsuji-trost allylic alkylation with ketone enolates.
PMID- 17029316
TI - On the species involved in the vaporization of imidazolium ionic liquids in a
steam-distillation-like process.
PMID- 17029318
TI - Highly luminescent ZnO nanocrystals stabilized by ionic-liquid components.
PMID- 17029317
TI - Aqueous-phase hydroformylation of 1-octene: styrene latices as phase-transfer
agents.
PMID- 17029319
TI - Optical sensors based on nanostructured cage materials for the detection of toxic
metal ions.
PMID- 17029320
TI - Noncrystalline metal-boron nanotubes: synthesis, characterization, and catalytic
hydrogenation properties.
PMID- 17029321
TI - Halogen-bridged PtII/PtIV mixed-valence ladder compounds.
PMID- 17029322
TI - Chiral neutral zirconium amidate complexes for the asymmetric hydroamination of
alkenes.
PMID- 17029323
TI - An FeVI nitride: there is plenty of room at the top!
PMID- 17029324
TI - Ion-induced biomolecular radiation damage: from isolated nucleobases to
nucleobase clusters.
AB - A large number of studies are devoted to the investigation of the biomolecular
ionization and fragmentation dynamics underlying biological radiation damage.
Most of these studies have been based on gas-phase collisions with isolated DNA
building blocks. The radiobiological significance of these studies is often
questioned because of the lack of a chemical environment. To clarify this aspect,
we studied interactions of keV ions with isolated nucleobases and with nucleobase
clusters by means of coincidence time-of-flight spectrometry. Significant changes
already show up in the molecular fragmentation patterns of very small clusters.
PMID- 17029325
TI - Identification of the D(3h) isomer of carbon trioxide (CO3) and its implications
for atmospheric chemistry.
AB - The CO3 molecule is considered an important reaction intermediate in the
atmospheres of Earth and Mars for quenching electronically excited oxygen atoms
and in contributing to the anomalous 18O isotope enrichment. The geometry of the
CO3 intermediate plays an important role in explaining these effects; however,
only the cyclic (C(2v)) isomer has been experimentally confirmed so far. Here, we
report on the first spectroscopic detection of the acyclic (D(3h)) isomer of
carbon trioxide (12C16O3) via its nu1 and nu2 vibrational modes centered around
1165 cm(-1) under matrix isolation conditions; the identification of the 12C18O3,
13C16O3, 13C18O3, 16O12C18O2, and 18O12C16O2 isotopomers of the acyclic isomer
confirms the assignments.
PMID- 17029327
TI - Notice of Retraction: "Autonomous histopathological regression of primary tumours
associated with specific immune responses to cancer antigens" (J Pathol 2003;
200: 383-395).
PMID- 17029326
TI - Redox-controlled photosensitization of nanocrystalline titanium dioxide.
AB - Photosensitization of nanocrystalline titanium dioxide materials has been
achieved by chemisorption of the pentacyanothiamineferrate(II) complex, which
offers a relatively high redox potential that determines the photoelectrochemical
properties of the photosensitized TiO(2). The adsorbed pentacyanoferrate complex
binds to TiO(2) through the cyanide bridge and forms a new surface complex
characterized by a metal-to-metal charge-transfer transition (MMCT) (Fe(II)-
>Ti(IV)). The photosensitization can be observed only at low potentials at which
Fe(II) moieties are present. Photocurrent switching between anodic and cathodic
can be induced by varying either the photoelectrode potential or the wavelength
of the incident light. Simple molecular modeling-together with spectroscopic and
electrochemical measurements-allows the elucidation of the mechanism of the
observed photoelectrochemical behavior.
PMID- 17029328
TI - Contrast-enhanced cardiac computed tomographic angiography in the diagnosis of
coronary artery stenosis or for evaluation of acute chest pain.
PMID- 17029329
TI - Special report: fecal DNA analysis for colon cancer screening.
PMID- 17029330
TI - Vagus nerve stimulation for treatment-resistance depression.
PMID- 17029331
TI - Posthumous paternity testing: a proposal to amend EPTL 4-1.2(a)(2)(D).
PMID- 17029332
TI - The interaction of law and psychiatry: a voyage over the ages.
PMID- 17029333
TI - Can angiographic vasospasm be used as a surrogate marker in evaluating
therapeutic interventions for cerebral vasospasm?
AB - The authors tested the null hypothesis that published literature with a high
level of evidence does not support the assertion that subarachnoid hemorrhage
(SAH) causes cerebral vasospasm, which in turn causes cerebral infarction and
poor outcome after aneurysmal SAH. The medical literature on SAH was searched in
MEDLINE. The author's personal files of all published literature on SAH were
reviewed. References cited in Cochrane reviews as well as the published papers
that were reviewed were also retrieved. There is no question that SAH causes what
the authors have chosen to call "angiographic vasospasm." However, the incidence
and severity of vasospasm in recent series of patients is not well defined. There
is reasonable evidence that vasospasm causes infarction, but again, accurate data
on how severe and how diffuse vasospasm has to be to cause infarction and how
often vasospasm is the primary cause of infarction are not available. There are
good data on the incidence of cerebral infarction after SAH, and these data
indicate that it is highly associated with poor outcome. The link between
angiographic vasospasm and poor outcome is particularly poorly described in terms
of what would be considered data of a high level of evidence. The question as to
whether there is a clear pathway from SAH to vasospasm to cerebral infarction to
poor outcome seems so obvious to neurosurgeons as to make it one not worth
asking. Nevertheless, the obvious is not always true or accurate, so it is
important to note that published literature only weakly supports the causative
association of vasospasm with infarction and poor outcome after SAH. It behooves
neurosurgeons to document this seemingly straightforward pathway with high
quality evidence acceptable to the proponents of evidence-based medicine.
PMID- 17029334
TI - Effects of acute treatment with statins on cerebral autoregulation in patients
after aneurysmal subarachnoid hemorrhage.
AB - OBJECT: The authors previously have demonstrated that acute treatment with
pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate
vasospasm-related delayed ischemic neurological deficits (DINDs). In the current
study, they test the hypothesis that these effects are associated with
improvement in indices describing autoregulation of cerebral blood flow. METHODS:
In this double-blind study, 80 patients between the ages of 18 and 84 years who
had aneurysmal SAH were randomized equally to receive either 40 mg of oral
pravastatin or placebo once daily for up to 14 days (medication was started 1.8 x
1.3 days after ictus). Autoregulation was measured using a daily transient
hyperemic response test (THRT) on transcranial Doppler ultrasonography (800
measurements in 80 patients), and data were compared between the pravastatin and
placebo groups and between patients with or without vasospasm, DINDs, or
unfavorable outcome. Measurement of autoregulation also was performed using the
pressure-reactivity index, a moving correlation coefficient between mean arterial
and intracranial pressures (Days 0-5, 132 measurements in 32 patients). There was
no difference in baseline autoregulation indices between the trial groups. The
members of the pravastatin group not only had a shorter duration of impaired
autoregulation but also had stronger transient hyperemic response ratios (THRRs)
bilaterally. A negative correlation existed between the mean flow velocity in the
middle cerebral artery and THRRs. Onset of DINDs occurred when bilateral
autoregulation failed. On Days 3, 4, and 5, the pressure-reactivity index
correlated significantly with ipsilateral impaired autoregulation. CONCLUSIONS:
The neuroprotective effects of acute treatment with pravastatin following
aneurysmal SAH are associated with enhancement of autoregulation. A routine and
daily assessment of cerebral autoregulation by using the THRT may help identify
patients at high risk of DINDs.
PMID- 17029335
TI - Effect of combined simvastatin and cyclosporine compared with simvastatin alone
on cerebral vasospasm after subarachnoid hemorrhage in a canine model.
AB - OBJECT: The object of this study was to determine whether the combination of
cyclosporine and simvastatin could ameliorate cerebral vasospasm after
subarachnoid hemorrhage (SAH) in a canine model to a greater extent than
simvastatin alone. METHODS: Animals were assigned to one of three groups: control
(five dogs), simvastatin alone (four), or simvastatin and cyclosporine (four). A
double SAH model was used. Baseline basilar artery (BA) angiograms were obtained.
These were repeated at Days 3, 7, and 10. Measurement of the BA diameter was
performed. Decreased BA diameter was seen on Day 3 in the control and
simvastatin/cyclosporine group. A return to baseline diameters was seen by Day 7.
An increase from baseline diameter was seen in the simvastatin group at Day 10.
CONCLUSIONS: Cyclosporine may interfere with the vasodilatory effects of
simvastatin. Vasodilation greater than baseline is seen at Day 10 in the
simvastatin group. The combination of simvastatin and cyclosporine does not
ameliorate cerebral vasospasm in a canine model to a greater extent than
simvastatin alone.
PMID- 17029336
TI - Update on endovascular therapies for cerebral vasospasm induced by aneurysmal
subarachnoid hemorrhage.
AB - Cerebral vasospasm remains a major source of morbidity and death in patients with
aneurysmal subarachnoid hemorrhage (SAH). When vasospasm becomes refractory to
maximal medical management consisting of induced hypertension and hypervolemia
and administration of calcium channel antagonists, endovascular therapies should
be considered. The primary goal of endovascular treatment is to increase cerebral
blood flow to prevent cerebral infarction. Two of the more frequently studied
endovascular treatments are transluminal balloon angioplasty and intraarterial
papaverine infusion. These two have been used either alone or in combination for
the treatment of vasospasm. Other pharmacological vasodilating agents currently
being investigated are intraarterial nimodipine, nicardipine, verapamil, and
milrinone. Newer intraarterial agents, such as fasudil and colforsin daropate,
have also been investigated. In this article the authors review the current
options in terms of endovascular therapies for treatment of cerebral vasospasm.
The mechanism of action, technique of administration, clinical effect and
outcomes, and complications of each modality are discussed.
PMID- 17029337
TI - Endovascular treatment strategies for cerebral vasospasm.
AB - Cerebral vasospasm is a significant cause of morbidity and mortality in patients
who have sustained a subarachnoid hemorrhage from aneurysm rupture. Symptomatic
cerebral vasospasm is also a strong predictor of poor clinical outcome and has
thus drawn a great deal of interest from cerebrovascular surgeons. Although
medical management is the cornerstone of treatment for this condition,
endovascular intervention may be warranted for those in whom this treatment fails
and in whom symptomatic vasospasm subsequently develops. The rapid advancements
in endovascular techniques and pharmacological agents used to combat this
pathological state continue to offer promise in broadening the available
treatment armamentarium. In this article the authors discuss the rationale and
basis for using the various endovascular options for the treatment of cerebral
vasospasm, and they also discuss the limitations, complications, and efficacy of
these treatment strategies in regard to neurological condition and outcome.
PMID- 17029338
TI - Safety and technical efficacy of over-the-wire balloons for the treatment of
subarachnoid hemorrhage-induced cerebral vasospasm.
AB - OBJECT: Over the past decade, low-pressure, flow-directed balloons have been
replaced by over-the-wire balloons in the treatment of vasospasm induced by
subarachnoid hemorrhage (SAH). The authors assess the procedural safety and
technical efficacy of these newer devices. METHODS: Seventy-five patients who
underwent 85 balloon angioplasty procedures for the treatment of SAH-induced
vasospasm were identified from a prospective quality-assurance database. Medical
records and angiographic reports were reviewed for evidence of procedural
complications and technical efficacy. No vessel rupture or perforation occurred,
but thromboembolic complications were noted in four (4.7%) of the 85 procedures.
Balloon angioplasty was frequently attempted and successfully accomplished in the
distal internal carotid (100%), proximal middle cerebral (94%), vertebral (73%),
and basilar (88%) arteries. Severe narrowing was present in 89 proximal anterior
cerebral arteries. Angioplasty was attempted in 41 of these vessels and was
successful in only 14 (34%). In 19 of the 27 unsuccessful attempts, the balloon
could not be advanced over the wire due to severe vasospasm or unfavorable vessel
angle. Follow-up angiography in a subset of patients demonstrated that severe
recurrent vasospasm occurred in 15 (13%) of 116 vessels studied after
angioplasty. CONCLUSIONS: Over-the-wire balloons involve a low risk for vessel
rupture. The anterior cerebral artery remains difficult to access and
successfully treat with current devices. Further improvements in balloon design,
such as smaller inflated diameters and better tracking, are necessary. Finally,
thromboembolic complications remain an important concern, and severe vasospasm
may recur after balloon angioplasty.
PMID- 17029339
TI - Effect of intraarterial verapamil on the diameter of vasospastic intracranial
arteries in patients with cerebral vasospasm.
AB - OBJECT: This study was conducted to determine whether there is a change in
intracranial arterial diameters after verapamil infusion for vasospasm and, if it
is present, to determine whether the change occurs in proximal, intermediate, or
distal vessels. METHODS: The authors measured arterial diameters in all patients
treated with intraarterial verapamil at their institutions between August 2003
and September 2004. In all, 18 treatments were examined in 15 patients.
Measurements were made before and after verapamil infusion in a blinded fashion
with the aid of a magnification loupe at nine predetermined arterial sites on
each angiogram. Baseline arterial measurements were made on each patient's
initial angiogram and on the angiogram demonstrating spasm prior to endovascular
therapy as well in 14 of the patients. Charts were retrospectively reviewed to
determine whether the patients benefited from intraarterial verapamil. From the
time of the initial angiogram to the time of vasospasm, there was a 21.6%
decrease (p = 0.092) in proximal artery diameter, a 47.1% decrease (p < 0.05) in
intermediate artery diameter, and a 12.4% decrease (p < 0.05) in distal artery
diameter. There were no significant changes in the diameters of proximal,
intermediate, or distal vessels after verapamil infusion (mean dose 7.4 mg, range
2.5-10 mg). After infusion of intraarterial verapamil, the proximal vessels
showed a 1.1% decrease in diameter, the intermediate vessels showed a 9.4%
increase, and the distal vessels showed a 3.3% decrease. CONCLUSIONS:
Administration of intraarterial verapamil does not cause a significant increase
in the diameter of vasospastic vessels at the administered doses.
PMID- 17029341
TI - Vasospasm as the sole cause of cerebral ischemia: how strong is the evidence?
AB - The authors review literature that challenges the view that vasospasm involving
large arteries is the exclusive cause of delayed ischemic neurological deficits
(DINDs) following subarachnoid hemorrhage. They discuss alternative mechanisms
and review the evidence supporting a potential role for thromboembolism. They
conclude that vasospasm and thromboembolism play interrelated and additive roles
in the development of DINDs, and that this interaction provides opportunities for
novel therapeutic approaches.
PMID- 17029340
TI - Effect of intraarterial papaverine and/or angioplasty on the cerebral veins in
patients with vasospasm after subarachnoid hemorrhage due to ruptured
intracranial aneurysms.
AB - OBJECT: The goal in this study was to determine if there was a change in
intracranial venous diameters after endovascular treatment of carotid
distribution vasospasm caused by subarachnoid hemorrhage. METHODS: The venous
diameters were measured in all patients who received intraarterial papaverine
and/or balloon angioplasty for treatment of vasospasm during the study period of
3 years. To evaluate the veins of Labbe and Trolard, the straight sinus, and the
superior sagittal sinus (SSS), measurements were performed in a blinded manner
with the aid of a magnification loupe. Predetermined sites were evaluated on
angiograms obtained before and after endovascular treatment. Forty-three
treatments in 26 patients were included: 18 patients (33 territories) were
treated with intraarterial papaverine alone, four (four territories) were treated
with balloon angioplasty alone, and four (six territories) were treated with both
papaverine infusion and angioplasty. The mean measured venous diameters increased
significantly after addition of papaverine (10.9%), and also after combined
papaverine and angioplasty (4.2%). There was no statistically significant
increase in the mean venous diameters after angioplasty alone. If the initial
intracranial pressure (ICP) was less than 15 mm Hg before treatment, the veins
showed a greater tendency to dilate than if the initial ICP measurements were
greater than 15 mm Hg. The straight sinus and the SSS increased more in diameter
than the veins of Labbe and Trolard. There was no statistically significant
correlation between the change in venous diameters with treatment and ICP.
CONCLUSIONS: Endovascular treatment produces measurable increases in intracranial
venous diameters. However, these changes do not correlate with changes in ICP.
PMID- 17029342
TI - Update on evidence for a genetic predisposition to cerebral vasospasm.
AB - Considerable evidence links cerebral vasospasm to the decreased bioavailability
of endothelial nitric oxide synthase (eNOS) after aneurysmal subarachnoid
hemorrhage (SAH). In recent studies from the cardiology literature, researchers
have suggested that a genetic predisposition to coronary vasospasm might develop
as the result of a T-786C single nucleotide polymorphism (SNP) in the eNOS gene.
The authors of this study attempted to determine if there may be a similar
genetic predisposition toward cerebral vasospasm. The authors prospectively
identified 28 patients with Fisher Grade 3 SAH from a group of 51 consecutive
patients with ruptured intracranial saccular aneurysms. Genomic DNA was isolated
from a peripheral blood sample obtained with permission from each patient. Gene
microarray technology was used to assay the samples for the presence and
distribution of certain key eNOS gene polymorphisms. Clinical, radiological, and
genomic data were analyzed. The finding of eNOS T-786C SNP could be used to
significantly differentiate between the presence and severity of cerebral
vasospasm (p = 0.04). The findings from this preliminary study support similar
findings in the coronary vasospasm literature as well as the hypothesis that a
predisposition toward cerebral vasospasm may be related partially to genetic
factors, which needs to be confirmed in a larger study. Such gene-based
information may be important in rapidly identifying patients at increased risk of
vasospasm after SAH, independent of their Fisher grade. In this article, the
authors review key studies in this area.
PMID- 17029344
TI - Computed tomography grading schemes used to predict cerebral vasospasm after
aneurysmal subarachnoid hemorrhage: a historical review.
AB - The elucidation of predictive factors of cerebral vasospasm following aneurysmal
subarachnoid hemorrhage (SAH) is a major area of both clinical and basic science
research. It is becoming clear that many factors contribute to this phenomenon.
The most consistent predictor of vasospasm has been the amount of SAH seen on the
postictal computed tomography scan. Over the last 30 years, it has become clear
that the greater the amount of blood within the basal cisterns, the greater the
risk of vasospasm. To evaluate this risk, various grading schemes have been
proposed, from simple to elaborate, the most widely known being the Fisher scale.
Most recently, volumetric quantification and clearance models have provided the
most detailed analysis. Intraventricular hemorrhage, although not supported as
strongly as cisternal SAH, has also been shown to be a risk factor for vasospasm.
PMID- 17029343
TI - Dissociation between vasospasm and functional improvement in a murine model of
subarachnoid hemorrhage.
AB - OBJECT: The efficacy of nimodipine was examined in a murine model of subarachnoid
hemorrhage (SAH). End points included the diameter of the lumen of the middle
cerebral artery (MCA) and behavioral outcome. An apolipoprotein E (apoE)-mimetic
peptide, acetyl-AS-Aib-LRKL-Aib-KRLL-amide, previously shown to have promise in
this model was tested both alone and in combination with nimodipine. The effects
of carboxyamidotriazole (CAI), a non-voltage-gated calcium channel blocker, were
explored using the same animal paradigm. METHODS: Experimental SAH was induced in
male C57B1/6J mice. For 3 days postoperatively, behavioral analyses were
performed. In the first experiment, the mice were treated with vehicle or with
low- or high-dose CAI for 3 days. In the second experiment, the mice were treated
with vehicle, high- and low-dose nimodipine, and/or the apoE-mimetic peptide. On
postoperative Day 3 each mouse was killed and perfused. Following this, the right
MCA was removed and its lumen measured. Mice that received nimodipine
demonstrated significant behavioral improvements when compared with vehicle
treated mice, but there was no clear dose-dependent effect on MCA diameter.
Administration of the apoE-mimetic peptide was associated with improved
functional performance and a significant reduction in vasospasm. Mice that
received high-dose CAI performed worse on functional tests, despite a significant
increase in the diameters of their MCA lumina. CONCLUSIONS: These results
demonstrate a dissociation between vasospasm and neurological outcomes that is
consistent with findings of previous clinical trials.
PMID- 17029345
TI - Utility of computed tomography perfusion in detection of cerebral vasospasm in
patients with subarachnoid hemorrhage.
AB - OBJECT: Digital subtraction (DS) angiography is the gold standard for detecting
cerebral vasospasm after subarachnoid hemorrhage (SAH). Computed tomography (CT)
perfusion is a recently developed modality for the evaluation of cerebral
hemodynamics. This study was conducted to evaluate the potential of using CT
perfusion to detect vasospasm in patients with SAH. METHODS: Fourteen patients
between the ages of 41 and 66 years with aneurysmal SAH underwent 23 CT perfusion
scans for suspected vasospasm. All patients underwent DS angiography within 12
hours of the CT perfusion scans. The presence of vasospasm on CT perfusion images
was determined based on qualitative reading using color maps of mean transit
time, cerebral blood flow, and cerebral blood volume as criteria. The presence or
absence of vasospasm as retrospectively determined using CT perfusion was
compared with DS angiography findings. Of the 23 CT perfusion scans performed, 21
(91%) were concordant with angiography findings in predicting the presence or
absence of vasospasm. In 15 of 23 scans, the presence of vasospasm was detected
on CT perfusion scans and confirmed on DS angiography studies. In two cases,
vasospasm was revealed on DS angiography but was not confirmed on CT perfusion.
The degree of agreement between CT perfusion and DS angiography for detection of
vasospasm was high (K = 0.8, p , 0.0001). CONCLUSIONS: Computed tomography
perfusion is an accurate, reliable, and noninvasive method to detect the presence
or absence of vasospasm. It can be used as a tool to help guide the decision to
pursue DS angiography with the intent to treat vasospasm.
PMID- 17029346
TI - Cerebral perfusion imaging in vasospasm.
AB - Vasospasm following cerebral aneurysm rupture is one of the most devastating
sequelae and the most common cause of delayed ischemic neurological deficit
(DIND). Because vasospasm also is the most common cause of morbidity and
mortality in patients who survive the initial bleeding episode, it is imperative
not only to diagnose the condition but also to predict which patients are likely
to become symptomatic. The exact pathophysiology of vasospasm is complex and
incompletely elucidated. Early recognition of vasospasm is essential because the
timely use of several therapeutic interventions can counteract this disease and
prevent the occurrence of DIND. However, the prompt implementation of these
therapies depends on the ability to predict impending vasospasm or to diagnose it
at its early stages. A number of techniques have been developed during the past
several decades to evaluate cerebral perfusion, including positron emission
tomography, xenon-enhanced computed tomography, single-photon emission computed
tomography, perfusion- and diffusion-weighted magnetic resonance imaging, and
perfusion computed tomography. In this article, the authors provide a general
overview of the currently available perfusion imaging techniques and their
applications in treating vasospasm after a patient has suffered a subarachnoid
hemorrhage. The use of cerebral perfusion imaging techniques for the early
detection of vasospasm is becoming more common and may provide opportunities for
early therapeutic intervention to counteract vasospasm in its earliest stages and
prevent the occurrence of DINDs.
PMID- 17029347
TI - Evidence-based cerebral vasospasm management.
AB - Cerebral vasospasm and delayed cerebral ischemia remain common complications of
aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral
vasospasm are limited. Despite a large number of clinical trials, only calcium
antagonists have strong evidence supporting their effectiveness. The purpose of
this work was to perform a systematic review of the literature on the treatment
of cerebral vasospasm. A literature search for randomized controlled trials of
therapies used for prevention or treatment of cerebral vasospasm and/or delayed
cerebral ischemia was conducted, and 41 articles meeting the review criteria were
found. Study characteristics and primary results of these articles are reviewed.
Key indicators of quality were poor when averaged across all studies, but have
improved greatly over time. The only proven therapy for vasospasm is nimodipine.
Tirilazad is not effective, and studies of hemodynamic maneuvers, magnesium,
statin medications, endothelin antagonists, steroid drugs,
anticoagulant/antiplatelet agents, and intrathecal fibrinolytic drugs have
yielded inconclusive results. The following conclusions were made: nimodipine is
indicated after SAH and tirilazad is not effective. More study of hemodynamic
maneuvers, the effectiveness of other calcium channel antagonists such as
nicardipine delivered by other routes (for example intrathecally), magnesium,
statin drugs, endothelin antagonists, and intrathecal fibrinolytic therapy is
warranted. There is less enthusiasm for the study of steroid drugs and
anticoagulant/antiplatelet agents because they entail more risks and
investigations so far have shown little evidence of efficacy. The study of rescue
therapy such as balloon angioplasty and intraarterial vasodilating agents will be
difficult. The quality of clinical trials should be improved.
PMID- 17029348
TI - A review of current and future medical therapies for cerebral vasospasm following
aneurysmal subarachnoid hemorrhage.
AB - In an effort to help clarify the current state of medical therapy for cerebral
vasospasm, the authors reviewed the relevant literature on the established
medical therapies used for cerebral vasospasm following aneurysmal subarachnoid
hemorrhage (SAH), and they discuss burgeoning areas of investigation. Despite
advances in the treatment of aneurysmal SAH, cerebral vasospasm remains a common
complication and has been correlated with a 1.5- to threefold increase in death
during the first 2 weeks after hemorrhage. A number of medical, pharmacological,
and surgical therapies are currently in use or being investigated in an attempt
to reverse cerebral vasospasm, but only a few have proven to be useful. Although
much has been elucidated regarding its pathophysiology, the treatment of cerebral
vasospasm remains a dilemma. Although a poor understanding of SAH-induced
cerebral vasospasm pathophysiology has, to date, hampered the development of
therapeutic interventions, current research efforts promise the eventual
production of new medical therapies.
PMID- 17029349
TI - Synthesis and reactivity of a new octanuclear iron-sulfur nitrosyl cluster.
AB - The synthesis and spectroscopic properties of (PPN)2[Fe8S6(NO)8] as well as its
reactivity toward sulfur are reported.
PMID- 17029350
TI - A traditional synthetic method, and a new structural motif, for molybdenum-gold
clusters: synthesis and solid-state structure of Au8{Mo(CO)5}4(PPh3)4.
AB - The neutral cluster [Au8Mo4(CO)20(PPh3)4] was synthesized in low yield from
[AuCl(PPh3)] and [Mo2(CO)10]2- in acetonitrile at room temperature. The cluster
was characterized by X-ray analysis, IR, and 31P NMR spectroscopy. Its solid
state structure consists of four Au(3)Mo tetrahedral units, fused by four Au
atoms in a ring. The average bond lengths are Au-Au 2.77 Angstrom and Mo-Au 2.93
Angstrom. The internal angles of the planar square ring are very close to 90
degrees.
PMID- 17029351
TI - New 3-D La(III)-Cu(II)-containing coordination polymer with a high potential
porosity.
AB - A new 3-D coordination polymer containing both 3d and 4f ions has been designed.
Its chemical formula is La2[Cu(pba)]3(H2O)8 . 8H2O. It crystallizes in the
quadratic system, space group I41/a with a = 42.4947(9) Angstrom, c = 16.3378(3)
Angstrom, and Z = 16. Its crystal structure can be described as a 3-D molecular
framework exhibiting a complex network of interconnected zigzaglike channels.
Once crystallization water molecules are removed, this compound presents a high
potential porosity and a low density. The porosity has been evaluated using
Connolly's algorithm.
PMID- 17029352
TI - First 3D 3d-4f interpenetrating structure: synthesis, reaction, and
characterization of {[LnCr(IDA)2(C2O4)]}n.
AB - The hydrothermal reaction of Cr(NO3)3, Ln2O3, and iminodiacetate acid (H(2)IDA)
in the molar ratio of 1:1:3 produced {[LnCr(IDA)2(C2O4)]}n (Ln = Eu, 1; Sm, 2),
which represent the first 3D 3d-4f interpenetrating coordination polymers. In the
reaction, the H(2)IDA ligands partly decompose into oxalate anions (ox), which
connect Ln(III) ions to form 1D {Ln(ox)}n chains. Each of the Cr(III) ions is
tridentate-coordinated by two IDA ligands, which act as tetradentate
metalloligands to link {Ln(ox)}n chains to form 3D open networks. The two open
networks interpenetrate each other to form nonporous products. 1 and 2 are
thermally stable up to 327 and 360 degrees C, respectively. Both of complexes
show normally paramagnetic behavior. The luminescent results imply that the
energy transfers from Ln(III) to Cr(III) are strong.
PMID- 17029353
TI - Intersite structural rearrangement of the blue copper site induced by substrate
binding: spectroscopic studies of a copper-containing nitrite reductase from
Alcaligenes xylosoxidans NCIMB 11015.
AB - A copper-containing nitrite reductase from Alcaligenes xylosoxidans NCIMB 11015
has its own unique blue or type 1 copper protein resonance Raman spectrum in the
usual Cu-S(Cys) stretching region, nu(Cu-S(Cys)), with a pair of strong peaks at
412 and 420 cm(-1) and a weak peak at 364 cm(-1). The predominantly nu(Cu-S(Cys))
Raman bands at 412, 420, and 364 cm(-1) of the type 1 copper site all shifted to
higher frequencies upon binding of nitrite to the type 2 copper site, and the
resonance Raman difference spectra progressively intensified with the increments
of nitrite ion concentration. Positive support for substrate binding to the type
2 copper is provided by the nu(Cu-S(Cys)) bands in the resonance Raman spectrum
of a type 2 copper-depleted enzyme, which is insensitive to the presence of NO2-.
The shift to higher frequency of the Raman bands of the type 1 copper center with
the addition of nitrite ions suggests a stronger Cu-S(Cys) interaction in the
substrate-bound A. xylosoxidans nitrite reductase.
PMID- 17029354
TI - An isolable, nonreducible high-valent manganese(V) imido corrolazine complex.
AB - The manganese(V) imido complex [(TBP8Cz)Mn(V)(NMes)] (2) was synthesized from the
Mn(III) complex [(TBP8Cz)Mn(III)] (1) and thermolysis of mesityl azide. An X-ray
structure of 2 reveals a short Mn-N distance [1.595(4) A], consistent with the Mn
N triple bond expected for a manganese(V) imido species. This high-valent species
is remarkably inert to one- and two-electron reductive processes such as NR group
transfer to alkenes or H-atom abstraction from O-H bonds. Electrochemical studies
support this lack of reactivity. In contrast, oxidation of 2 is easily
accomplished by treatment with [(4-BrC6H4)3N]*+SbCl6, giving a pi-radical-cation
complex.
PMID- 17029355
TI - Nonfluorinated volatile copper(I) 1,3-diketiminates as precursors for Cu metal
deposition via atomic layer deposition.
AB - Novel nonfluorinated Cu(diketiminate)L complexes with L = neutral olefinic ligand
have been prepared as stable, volatile Cu(I) precursors for the deposition of
copper films by an atomic layer deposition (ALD) process. Among them, the
complexes of 4-a and 5-a are the most volatile and stable at low temperature (55
degrees C). A clean, conformal copper film was deposited at 120 degrees C in an
ALD process. These Cu(I) complexes are the first examples of nonfluorinated
copper(I) diketiminates that can be readily applied to an industrial
microelectronic fabrication process.
PMID- 17029356
TI - The structure and synthesis of plutonium(III) chlorides from aqueous solution.
AB - The preparation and structure of three trivalent plutonium chloride compounds
from aqueous solution is reported. Two of the three are plutonium
tetraaquatetrachloro complexes exhibiting a cis and a trans arrangement of Cl
about the Pu. The identification of the coordination number of 4 with respect to
Cl and the isomerism are both unprecedented in actinide solution chemistry. The
third complex is a hexaaquadichloro complex of Pu(III), predicted by available
thermodynamic data.
PMID- 17029357
TI - Luminescent 2-D double-layered polymer, [(CuI)4(CH3SCH3)3]infinity, containing
helical chains constructed by flower-basket-shaped Cu4I4 clusters.
AB - A new route for the synthesis of coordination compounds with dimethyl sulfide
ligand is reported; the prepared compound is a novel 2-D framework with a 1-D
right-handed and left-handed helical structure, which is unique in the sense that
the fundamental units are unusual Cu4I4 clusters.
PMID- 17029358
TI - Synthesis and characterization of a doxorubicin-Gd(III) contrast agent conjugate:
a new approach toward prodrug-procontrast complexes.
AB - We have prepared the first MRI prodrug-procontrast complex by conjugating
doxorubicin to a Gd(III) chelate using an acid-labile linker. The relaxometric
properties of the adduct and pH activation are reported.
PMID- 17029359
TI - Ultrahigh-field NMR spectroscopy of quadrupolar transition metals: 55Mn NMR of
several solid manganese carbonyls.
AB - 55Mn NMR spectra acquired at 21.14 T (nu(L)(55Mn) = 223.1 MHz) are presented and
demonstrate the advantages of using ultrahigh magnetic fields for characterizing
the chemical shift tensors of several manganese carbonyls: eta5-CpMn(CO)3,
Mn2(CO)10, and (CO)5MnMPh3 (M = Ge, Sn, Pb). For the compounds investigated, the
anisotropies of the manganese chemical shift tensors are less than 250 ppm except
for eta5-CpMn(CO)3, which has an anisotropy of 920 ppm. At 21.14 T, one can
excite the entire m(I) = 1/2 <--> m(I) = -1/2 central transition of eta5
CpMn(CO)3, which has a breadth of approximately 700 kHz. The breadth arises from
second-order quadrupolar broadening due to the 55Mn quadrupolar coupling constant
of 64.3 MHz, as well as the anisotropic shielding. Subtle variations in the
electric field gradient tensors at the manganese are observed for
crystallographically unique sites in two of the solid pentacarbonyls, resulting
in measurably different C(Q) values. MQMAS experiments are able to distinguish
four magnetically unique Mn sites in (CO)(5)MnPbPh3, each with slightly different
values of delta(iso), C(Q), and eta(Q).
PMID- 17029360
TI - Metal-binding thermodynamics of the histidine-rich sequence from the metal
transport protein IRT1 of Arabidopsis thaliana.
AB - The widespread ZIP family of transmembrane metal-transporting proteins is
characterized by a large intracellular loop that contains a histidine-rich
sequence whose biological role is unknown. To provide a chemical basis for this
role, we prepared and studied a peptide corresponding to this sequence from the
first iron-regulated transporter (IRT1) of Arabidopsis thaliana, which transports
Fe2+ as well as Mn2+, Co2+, Zn2+, and Cd2+. Isothermal titration calorimetry
(ITC) measurements, which required novel experiments and data analysis, and
supporting spectroscopic methods were used to quantify IRT1's metal-binding
affinity and associated thermodynamics. The peptide, PHGHGHGHGP, binds metal ions
with 1:1 stoichiometry and stabilities that are consistent with the Irving
Williams series. Comparison of the metal-binding thermodynamics of the peptide
with those of trien provides new insight about enthalpic and entropic
contributions to the stability of the metal-peptide complex. Although Fe2+ and
other IRT1-transported metal ions do not bind very tightly, this His-rich
sequence has a very high entropy-driven affinity for Fe3+, which may have
biological significance.
PMID- 17029361
TI - Computational comparison of cation coordination to human prion peptide models.
AB - The coordination of the cations Cu(II), Co(II), Rh(III), Ir(III), Ni(II), Pd(II),
Pt(II), and Zn(II) to the copper-binding octapeptide region in the human prion
protein has been compared through structural optimization. The initial
coordination mode used in the calculations is a five-coordinated mode obtained
from previously published crystallographic data for Cu(II). The computational
results show that, among these cations, the coordinations of Co(II) and Rh(III)
are the most similar to that of Cu(II). The cations Ni(II), Pd(II), and Pt(II)
prefer a four-coordinate square-planar coordination by the peptide ligand. The
paramagnetic Co(II) ion with its large quadrupole moment is not a good substitute
for Cu(II) to be used in NMR spectroscopic studies of the coordinated peptide
region. Rh(III) has more attractive NMR spectroscopic characteristics than Cu(II)
and Co(II) and may represent a suitable substitute for Cu(II) in these types of
studies. Some preliminary experimental studies using NMR spectroscopic methods
indicate that Rh(III) coordinates the copper-binding octapeptide region of the
human prion protein, although further studies are required to determine the mode
of interaction in detail.
PMID- 17029362
TI - Toward a clear-cut vision on the origin of 2,6-di(1,2,4-triazin-3-yl)pyridine
selectivity for trivalent actinides: insights from theory.
AB - Although BTP (2,6-di(1,2,4-triazin-3-yl)pyridine) has been widely evidenced as
the most effective nitrogen ligand for the selective complexation of trivalent
actinides from lanthanide counterparts, the origin of its selectivity is still an
open question. Neither experimental data nor theoretical calculations have been
able to rationalize the role of covalency in real experimental BTP complexes. We
show herein with DFT calculations on [M(BTP)3]3+ (M = La, U, Cm, Gd) that, even
if back-bonding effects are significant in the U-BTP bond, it is the contrast of
donation on 6d and 5f Cm(III) orbitals that explains, at least in part, its
selective complexation to BTP.
PMID- 17029363
TI - Syntheses, structures, and photoluminescence properties of metal(II) halide
complexes with pyridine-containing flexible tripodal ligands.
AB - Seven coordination compounds, [Zn(L3)Cl2] . MeOH . H2O (1), [Mn(L3)2Cl2] .
0.5EtOH . 0.5H2O (2), [Cu3(L2)2Cl6] . 2DMF (3), [Cu3(L2)2Br6] . 4MeOH (4),
[Hg2(L4)Cl4] (5), [Hg2(L4)Br4] (6), and [Hg3(L4)2I6] . H2O (7), were synthesized
by the reactions of ligands 1,3,5-tris(3-pyridylmethoxyl)benzene (L3), 1,3,5
tris(2-pyridylmethoxyl)benzene (L2), and 1,3,5-tris(4-pyridylmethoxyl)benzene
(L4) with the corresponding metal halides. All the structures were established by
single-crystal X-ray diffraction analysis. In complexes 1 and 2, L3 acts as a
bidentate ligand using two of three pyridyl arms to link two metal atoms to
result in two different 1D chain structures. In complexes 3 and 4, each L2 serves
as tridentate ligand and connects three Cu(II) atoms to form a 2D network
structure. Complexes 5 and 6 have the same framework structure, and L4 acts as a
three-connecting ligand to connect Hg(II) atoms to generate a 3D 4-fold
interpenetrated framework, while the structure of complex 7 is an infinite 1D
chain. The results indicate that the flexible ligands can adopt different
conformations and thus can form complexes with varied structures. In addition,
the coordination geometry of the metal atom and the species of the halide were
found to have great impact on the structure of the complexes. The
photoluminescence properties of the complexes were investigated, and the Zn(II),
Mn(II) and Hg(II) complexes showed blue emissions in solid state at room
temperature.
PMID- 17029365
TI - Necklace-like hollow carbon nanospheres from the pentagon-including reactants:
synthesis and electrochemical properties.
AB - Necklace-like hollow carbon nanospheres (CNSs) have been successfully synthesized
from the pentagon-including reactants, which provide an auxiliary example for the
theoretical prediction that necklace-like hollow CNSs are assumed to be composed
of the regular occurrence of nonhexagonal rings at the atomic level. Benefits of
the as-obtained hollow CNSs also arise from the high Brunauer-Emmett-Teller value
of 594.32 m(2)/g and a narrow pore distribution at 5 nm. The electrochemical
hydrogen storage experiments for the as-obtained necklace-like hollow CNSs
exhibit a capacity of 242 mAh/g at the current density of 200 mA/g, corresponding
to a hydrogen storage of 0.89 wt %, which is higher than the previously reported
electrochemical capacities for the multiwalled carbon nanotubes (MWCNTs).
Furthermore, the as-obtained necklace-like hollow CNSs show a lithium capacity
advantage compared with the carbon solid particles for application in lithium
batteries. These results indicate that the necklace-like hollow CNSs provide a
new candidate for the application in hydrogen storage and lithium batteries.
PMID- 17029364
TI - Density functional theory study of Fe(IV) d-d optical transitions in active-site
models of class I ribonucleotide reductase intermediate X with vertical self
consistent reaction field methods.
AB - The Fe(IV) d-d transition energies for four active-site structural models of
class I ribonucleotide reductase (RNR) intermediate X have been calculated using
broken-symmetry density functional theory incorporated with the Slater transition
state vertical self-consistent reaction field methodology. Our model I (Figure
1), which contains two mu-oxo bridges, one terminal water, and one bidentate
carboxylate group, yields the best Fe(IV) d-d transition energies compared with
experiment. Our previous study (J. Am. Chem. Soc. 2005, 127, 15778-15790) also
shows that most of the other calculated properties of model I in both native and
mutant Y122F forms, including geometries, spin states, pKa's, 57Fe, 1H, and 17O
hyperfine tensors, and 57Fe Mossbauer isomer shifts and quadrupole splittings,
are also the best in agreement with the available experimental data. This model
is likely to represent the active-site structure of the intermediate state X of
RNR.
PMID- 17029366
TI - Isomeric distribution and catalyzed isomerization of cobalt(III) complexes with
pentadentate macrocyclic ligands. importance of hydrogen bonding.
AB - We have investigated the isomeric distribution and rearrangement of complexes of
the type [CoXLn]2+,3+ (where X = Cl-, OH-, H2O, and Ln represents a pentadentate
13-, 14-, and 15-membered tetra-aza or diaza-dithia (N4 or N2S2) macrocycle
bearing a pendant primary amine). The preparative procedures for chloro complexes
produced almost exclusively kinetically preferred cis isomers (where the pendant
primary amine is cis to the chloro ligand) that can be separated by careful
cation-exchange chromatography. For L13 and L14 the so-called cis-V isomer is
isolated as the kinetic product, and for L15 the cis-VI form (an N-based
diastereomer) is the preferred, while for the L14(S) complex both cis-V and trans
I forms are obtained. All these complexes rearrange to form stable trans isomers
in which the pendent primary amine is trans to the monodentate aqua or hydroxo
ligand, depending on pH and the workup procedure. In total 11 different complexes
have been studied. From these, two different trans isomers of [CoClL14(S)]2+ have
been characterized crystallographically for the first time in addition to a new
structure of cis-V-[CoClL14(S)]2+; all were isolated as their chloride
perchlorate salts. Two additional isomers have been identified and characterized
by NMR as reaction intermediates. The remaining seven forms correspond to the
complexes already known, produced in preparative procedures. The kinetic,
thermal, and baric activation parameters for all the isomerization reactions have
been determined and involve large activation enthalpies and positive volumes of
activation. Activation entropies indicate a very important degree of hydrogen
bonding in the reactivity of the complexes, confirmed by density functional
theory studies on the stability of the different isomeric forms. The
isomerization processes are not simple and even some unstable intermediates have
been detected and characterized as part of the above-mentioned 11 forms of the
complexes. A common reaction mechanism for the isomerization reactions has been
proposed for all the complexes derived from the observed kinetic and solution
behavior.
PMID- 17029367
TI - Investigation of the pronounced medium effects observed in the voltammetry of the
highly charged lacunary anions [alpha-SiW11O39]8- and [alpha-PW11O39]7-.
AB - A detailed study is reported of the influence of protons, metal cations, and
media on the redox chemistry of lacunary anions [alpha-SiW11O39]8- and [alpha
PW11O39]7- of high formal negative charge. Each anion displayed a single
chemically reversible one-electron reduction process in carefully dried aprotic
CH3CN solution. This process was detected at very negative potentials just prior
to the solvent limit. Addition of 0.3 equiv of acid gave rise to a new reduction
process at considerably less negative potentials, which is attributed to
formation of the protonated species [SiW11O38(OH)]7- and [PW11O38(OH)]6-.
Voltammograms derived from simulations based on a double-square scheme are in
excellent agreement with experiment. Previous data reported the presence of
several processes in CH3CN and appear to have been influenced by the presence of
protons and/or adventitious water. Not surprisingly, protonation reactions
coupled to charge transfer contribute significantly to the voltammetry of these
lacunary anions in buffered aqueous media over the pH range 2-6. A multi-square
scheme mechanism allowed the essential thermodynamic and kinetic features of this
system to be captured and an assessment of the relative significance of possible
individual pathways. The high formal anionic charges of [SiW11O39]8- and
[PW11O39]7- appear to provide highly basic reduced forms that are able to
abstract protons from water to produce protonated species which are reduced at
potentials more than a volt less negative than those for the processes
[SiW11O39]8-/9- and [PW11O39]7-/8- found in dry aprotic media.
PMID- 17029368
TI - Dilacunary decatungstates functionalized by organometallic ruthenium(II),
[{Ru(C6H6)(H2O)}{Ru(C6H6)}(gamma-XW10O36)]4- (X = Si, Ge).
AB - The benzene-Ru(II)-supported dilacunary decatungstosilicate
[{Ru(C6H6)(H2O)}{Ru(C6H6)}(gamma-SiW10O36)]4- and the isostructural
decatungstogermanate [{Ru(C6H6)(H2O)}{Ru(C6H6)}(gamma-GeW10O36)]4- have been
synthesized and characterized by multinuclear solution NMR, IR, elemental
analysis, and electrochemistry. Single-crystal X-ray analysis was carried out on
K4[{Ru(C6H6)(H2O)}{Ru(C6H6)}(gamma-SiW10O36)].9H2O (K-1), which crystallizes in
the orthorhombic system, space group Pmn2(1), with a = 13.6702(3) A, b =
16.2419(4) A, c = 12.1397(2) A, and Z = 2, and on
K4[{Ru(C6H6)(H2O)}{Ru(C6H6)}(gamma-GeW10O36)].7H2O (K-2), which also crystallizes
in the orthorhombic system, space group Pmn2(1), with a = 13.6684(12) A, b =
16.297(2) A, c = 12.1607(13) A, and Z = 2. Polyanions 1 and 2 consist of a
Ru(C6H6)(H2O) group and a Ru(C6H6) group linked to a dilacunary (gamma-XW10O36)
Keggin fragment resulting in an assembly with idealized Cs symmetry. The
Ru(C6H6)(H2O) group is bound at the lacunary polyanion site via two Ru-O(W)
bonds, whereas the Ru(C6H6) group is bound on the side via three Ru-O(W) bonds.
Polyanions 1 and 2 were synthesized in aqueous acidic medium at pH 2.5 by the
reaction of [Ru(C6H6)Cl2]2 with [gamma-SiW10O36]8- and [gamma-GeW10O36]8-,
respectively. The formal potentials are roughly the same for the first W waves of
1 and 2. However, important differences appear for the second W waves. These
observations indicate different acid-base properties for the reduced forms of 1
and 2. Three oxidation processes were detected: the oxidation of the Ru center is
followed first by irreversible electrocatalytic processes of the Ru-benzene
moiety and then of the electrolyte. Comparison of this behavior with that of the
precursor reagent, [Ru(C6H6)Cl2]2, was useful to understand the main oxidation
processes. A ligand substitution reaction was observed upon addition of dimethyl
sulfoxide (dmso) to 1, 2, or [Ru(C6H6)Cl2]2. This reaction facilitates
substantially the oxidation of the Ru center. The dmso was oxidized with large
electrocatalytic currents more efficiently in the presence of 1 and 2 than with
[Ru(C6H6)Cl2]2.
PMID- 17029369
TI - Synthesis, structure, and photophysical properties of luminescent platinum(II)
complexes containing cyclometalated 4-styryl-functionalized 2-phenylpyridine
ligands.
AB - A series of new luminescent cyclometalated platinum(II) complexes functionalized
with various substituted styryl groups on the cyclometallating ligand [Pt(C/?N
ppy-4-styryl-R)(O/?O-(O)CCR'CHCR'C(O))] (ppy-4-styryl-R = E-4(4-(R)styryl-2
phenylpyridine) (3, R' = Me (acac); 4, R' = (t)Bu (dpm); R = H, OMe, NEt2, NO2)
have been prepared. All complexes undergo an E-Z photoisomerization process in
CH2Cl2 solution under sunlight, as monitored by 1H NMR. The solid-state
structures of 3-OMe, 3-NEt2, 3-NO2, and 4-OMe have been determined by X-ray
diffraction studies and compare well with optimized geometries obtained by
density functional theory (DFT) calculations. The orbital pictures of 3-H, 3-OMe,
and 3-NO 2 are very similar, the highest occupied molecular orbital (HOMO) being
highly Pt(5d) metal-based. For 3-NMe2, an additional contribution from the amino
styryl fragment leads to a decreased metal parentage of the HOMO, suggesting a
predominantly ILCT character transition. Complexes 3-H, 3-OMe, and 3-NO2 show a
low-energy band (350-400 nm) assigned to predominantly charge-transfer
transitions. The amino derivative 3-NEt2 displays a very strong absorption band
at 432 nm, tentatively assigned to a mixture of ILCT (Et2N --> CH=CH) and metal
to-ligand charge-transfer (MLCT) (dpi(Pt) --> pi) transitions. Complexes 3 are
weakly luminescent in CH2Cl2 solution at room temperature; the low intensity may
be due to a competitive quenching through the E-Z photoisomerization process. All
complexes exhibit similar structured emission bands under these conditions
(around 520 nm), independent of the nature of the styryl-R group. In a frozen EPA
glass (77 K), the spectrum of the representative complex 3-H exhibits two sets of
vibronically structured bands (460-560, 570-800 nm; lambda(max) = 596 nm), due to
the presence of two emitting species, the E and Z isomers, which have
significantly different triplet excited-state energies. The other three complexes
show similar behavior to 3-H at 77 K, but the lower-energy emission bands are
progressively red-shifted in the order H < OMe < NO2 < NEt2 (e.g., for 3-NEt2,
lambda(max)(em) = 658 nm; tau = 26 micros). The very large red-shift compared to
related unsubstituted complexes (e.g., to [Pt(C/?N-ppy)(O/?O-acac)]) is the
result of the extension of the pi-conjugated system and the electronic effects of
substituent R.
PMID- 17029371
TI - New ruthenium nitrosyl complexes with tris(1-pyrazolyl)methane (tpm) and 2,2'
bipyridine (bpy) coligands. Structure, spectroscopy, and electrophilic and
nucleophilic reactivities of bound nitrosyl.
AB - The new compound [Ru(bpy)(tpm)NO](ClO4)3 [tpm = tris(1-pyrazolyl)methane; bpy =
2,2'-bipyridine] has been prepared in a stepwise procedure that involves the
conversion of [Ru(bpy)(tpm)Cl]+ into the aqua and nitro intermediates, followed
by acidification. The diamagnetic complex crystallizes to exhibit distorted
octahedral geometry around the metal, with the Ru-N(O) bond length 1.774(12) A
and the RuNO angle 179.1(12) degrees , typical for a {RuNO}6 description. The
[Ru(bpy)(tpm)NO]3+ ion (I) has been characterized by 1H NMR and IR spectroscopies
(nu(NO) = 1959 cm(-1)) and through density functional theory calculations.
Intense electronic transitions in the 300-350-nm region are assigned through time
dependent (TD)DFT as intraligand pi --> pi for bpy and tpm. The dpi --> pi(bpy)
metal-to-ligand charge-transfer transitions appear at higher energies. Aqueous
cyclic voltammetric studies show a reversible wave at 0.31 V (vs Ag/AgCl, 3 M Cl
), which shifts to 0.60 V in MeCN, along with the onset of a wave of an
irreversible process at -0.2 V. The waves are assigned to the one- and two
electron reductions centered at the NO ligand, leading to species with {RuNO}(7)
and {RuNO}(8) configurations, respectively. Controlled potential reduction of I
in MeCN led to the [Ru(bpy)(tpm)NO]2+ ion (II), revealing a significant downward
shift of nu(NO) to 1660 cm(-1) as well as changes in the electronic absorption
bands. II was also characterized by electron paramagnetic resonance, showing an
anisotropic signal at 110 K that arises from an S = 1/2 electronic ground state;
the g-matrix components and hyperfine coupling tensor resemble the behavior of
related {RuNO}7 complexes. Both I and II were characterized through their main
reactivity modes, electrophilic and nucleophilic, respectively. The addition of
OH- into I generated the nitro complex, with k(OH) = 3.05 x 10(6) M(-1) s(-1) (25
degrees C). This value is among the highest obtained for related nitrosyl
complexes and correlates with ENO+/NO, the one-electron redox potential. Complex
II is a robust species toward NO release, although a conversion to I was observed
in the presence of O2. This reaction afforded a second-order rate law with k =
3.5 M(-1) s(-1) (25 degrees C). The stabilization of the NO radical complex is
attributed to the high positive charge of the precursor and to the geometrical
and electronic structure as determined by the neutral tpm ligand.
PMID- 17029372
TI - Inorganic asymmetric synthesis: asymmetric synthesis of a two-bladed propeller,
octahedral metal complex.
AB - A C2 hexadentate, in which two pyridine-2-aldehyde 2'-pyridylhydrazone (PAPHY)
groups are linked to a chiral auxiliary derived from (R,R)-tartaric acid, (R,R)
1, reacts with iron(II) benzenesulfonate to give the two-bladed propeller,
octahedral complex (P(Fe))-[Fe{(R,R)-1}](PhSO3)2 with complete
diastereoselectivity, as determined by 1H NMR spectroscopy and X-ray
crystallography. Saponification of the ester linkages and deprotonation of the
hydrazone-NH groups in the configurationally pure diastereomer affords the
complex (P(Fe))-[Fe(5-HOCH2PAPY)2] with 85% retention of configuration at the
iron stereocenter, as determined by reprotonation of the neutral complex with
enantiomerically pure (aR)-binaphthyl phosphoric acid and analysis of the 1H NMR
spectrum of the mixture of diastereomeric salts produced. This is the first
asymmetric synthesis of a two-bladed propeller, octahedral metal complex by the
classical organic methodology of chiral auxiliary-directed, asymmetric synthesis.
PMID- 17029370
TI - Pseudotetrahedral manganese complexes supported by the anionic
tris(phosphino)borate ligand [PhBP(iPr)3].
AB - This paper presents aspects of the coordination chemistry of mono- and divalent
manganese complexes supported by the anionic tris(phosphino)borate ligand,
[PhBP(i)(Pr)3] (where [PhBP(i)(Pr)3] = [PhB(CH(2)P(i)Pr2)3]-). The Mn(II) halide
complexes, [PhBP(i)(Pr)3]MnCl (1) and [PhBP(i)(Pr)3]MnI (2), have been
characterized by X-ray diffraction, SQUID magnetometry, and EPR spectroscopy.
Compound 2 serves as a precursor to a series of Mn azide, alkyl, and amide
species: [PhBP(i)(Pr)3]Mn(N3) (3), [PhBP(i)(Pr)3]Mn(CH2Ph) (4),
[PhBP(i)(Pr)3]Mn(Me) (5), [PhBP(i)(Pr)3]Mn(NH(2,6-(i)Pr2-C6H3)) (6),
[PhBP(i)(Pr)3]Mn(dbabh) (7), and [PhBP(i)(Pr)3]Mn(1-Ph(isoindolate)) (8). The
complexes 2-8 feature a divalent-metal center and are pseudotetrahedral. They
collectively represent an uncommon structural motif for low-coordinate,
polyphosphine-supported Mn complexes. Two Mn(I) species have also been prepared.
These include the Tl-Mn adduct [PhBP(i)(Pr)3]Tl-MnBr(CO)4 (9) and the octahedral
complex [PhBP(i)(Pr)3]Mn(CN(t)Bu)3 (10). Some of our initial synthetic efforts to
generate [PhBP(i)(Pr)3]MnN(x) species are briefly described, as are DFT studies
that probe the electronic viability of these types of multiply bonded target
structures.
PMID- 17029373
TI - Formation of p-phenylenediamine-crown ether-[PMo12O40]4- salts.
AB - Electron transfer from the electron donor of p-phenylenediamine (PPD) to the
electron acceptor of (H+)3[PMo12O40]3- forms a one-electron-reduced Keggin
cluster of [PMo12O40]4-, bearing a S = 1/2 spin, while proton transfer from the
proton donor of (H+)3[PMo12O40]3- to the proton acceptor of PPD yielded mono- and
diprotonated cations of 4-aminoanilinium (HPPD+) and p-phenylenediammonium
(H2PPD2+). By introduction of crown ether receptors during the crystallization
process, supramolecular cations of (HPPD+)(crown ethers) and/or (H2PPD2+)(crown
ethers) were successfully introduced into three new alpha-[PMo12O40]4- salts of
(H2PPD2+)2([12]crown-4)4[PMo12O40]4- (1), (HPPD+)4([15]crown-5)4[PMo12O40]4- (2),
and (HPPD+)2(H2PPD2+)([18]crown-6)4[PMo12O40]4- (3) as the countercation. The
protonated states of PPD and molecular-assembly structures of the supramolecular
cations depended on the size of the crown ethers. In salt 3, a novel mixed
protonated state of HPPD+ and H2PPD2+ was confirmed to be complexed in the cation
structure. According to the changes in the cation structures, the anion
arrangements were modulated from those of the two-dimensional layer for salt 1 to
the isolated cluster for salts 2 and 3. The temperature-dependent magnetic
susceptibilities of salts 1-3 were consistent with the isolated spin arrangements
of [PMo12O40]4-. The electronic spectra of salts 1-3 indicated the intervalence
optical transition from pentavalent Mo(V) to hexavalent Mo(VI) ions within the
[PMo12O40]4- cluster. Temperature-dependent electron spin resonance spectra of
salt 2 revealed the delocalization-localization transition of the S = 1/2 spin at
60 K. The spin on the [PMo12O40]4- cluster was localized on a specific Mo(V) site
below 60 K, which was thermally activated with an activation energy of 0.015 eV.
PMID- 17029374
TI - Syntheses, structures, and nonlinear optical properties of heteroselenometallic W
Se-Ag cluster compounds containing phosphine ligands.
AB - Treatment of [Et4N]2[WSe4] with a 1:1 mixture of AgNO3 and PCy3 (Cy = cyclohexyl)
in the absence of iodide afforded a linear trinuclear compound [(mu
WSe4)(AgPCy3)2] (1). A similar reaction in the presence of iodide gave rise to
the isolation of the cubanelike compound [(mu3-WSe4)Ag3(PCy3)3(mu3-I)] (2).
Treatment of [Et4N]2[WSe4] with AgI in the presence of bidentate phosphine
ligands bis(diphenylphosphino)amine (dppa) and bis(diphenylphosphino)methane
(dppm) afforded the tetranuclear compounds [(mu3-WSe4)Ag3(mu-I)(mu-dppa)2] (3)
and [(mu3-WSe4)Ag3(mu3-I)(mu-dppm)2] (4), respectively, which exhibit an open
butterfly configuration. A novel hexanuclear cluster compound [(mu3-WSe4)2Ag4(mu
dppm)3] (5) was obtained from interaction of [Et4N]2[WSe4] with AgNO3 and dppm in
the absence of iodide source. The above cluster compounds are electrically
neutral and air-stable in both solution and the solid state and have been
characterized by electronic, infrared, mass, and NMR spectroscopies. The solid
state structures of five cluster compounds have been established by X-ray
crystallography. The nonlinear optical properties of compounds 4 and 5 were
examined by z-scan techniques with 7 ns pulses at 532 nm. The optical limiting
effects of compounds 1, 2, 4, and 5 were determined and compared with related
argentoselenometallic compounds.
PMID- 17029375
TI - Infrared spectra of the M(NO)n (M = Sn, Pb; n = 1, 2) and PbNO- molecules.
AB - Reactions of laser-ablated tin and lead atoms with nitric oxide molecules in
solid argon and neon have been investigated using matrix-isolation infrared
spectroscopy. In the argon experiments, absorptions at 1560.1, 1625.8, and 1486.7
cm(-1) are assigned to the N-O stretching vibrations of the SnNO and Sn(NO)2
molecules, and absorptions at 1541.9, 1630.0, 1481.8, and 1457.5 cm(-1) are
assigned to the N-O stretching vibrations of the PbNO, Pb(NO)2, and PbNO-
molecules on the basis of isotopic shifts and splitting patterns. The present
neon experiments only produce neutral tin and lead mononitrosyls. Density
functional theory calculations have been performed on these tin and lead
nitrosyls. The good agreement between the experimental and calculated vibrational
frequencies, relative absorption intensities, and isotopic shifts substantiates
the identification of these nitrosyls from the matrix infrared spectra.
PMID- 17029376
TI - Catalysts for monooxygenations made from polyoxometalate: an iron(V)-oxo
derivative of the Lindqvist anion.
AB - This work uses density functional calculations to design a new high-valent
Fe(V)=O catalyst [Mo5O18Fe=O]3-, which is based on the Lindqvist polyoxometalate
(Mo6O19(2-)). Because the parent species is stable to oxidative conditions, one
may assume that the newly proposed iron-oxo species will be stable, too. The
calculated Mossbauer spectroscopic data may be helpful toward an eventual
identification of the species. The calculations of C-H hydroxylation and C=C
epoxidation of propene show that, if made, [Mo5O18Fe=O]3- should be a potent
oxidant that will be subject to strong solvent effect. Moreover, the Lindqvist
catalyst leads to an intriguing result; the reaction that starts along an
epoxidation pathway with C=C activation ends with a C-H hydroxylation product
((4)6) due to rearrangement on the catalyst. The origins of this result are
analyzed in terms of the structure of the catalyst and the electronic
requirements for conversion of an epoxidation intermediate to a hydroxylation
product. Thus, if made, the [Mo5O18Fe=O]3 will be a selective C-H hydroxylation
reagent.
PMID- 17029377
TI - Cadmium(II) and zinc(II) complexes of S-confused thiaporphyrin.
AB - The synthesis of 5,10,15,20-tetraphenyl-2-thia-21-carbaporphyrin [S-confused
thiaporphyrin, (SCPH)H] was optimized. The formation of the phlorin was detected,
which was saturated at the meso carbon adjacent to thiophene. Phlorin converted
readily to (SCPH)H in the final oxidation process. Insertion of cadmium(II) and
zinc(II) into S-confused thiaporphyrin yielded (SCPH)Cd(II)Cl and (SCPH)Zn(II)Cl
complexes. The macrocycle acted as a monoanionic ligand. Three nitrogen atoms and
the C(21)H fragment of the inverted thiophene occupied equatorial positions. The
compensation of the metal charge required the apical chloride coordination. The
characteristic C(21)H resonances of the inverted thiophene ring were located at
1.71 and 1.86 ppm in the 1H NMR spectra of (SCPH)Cd(II)Cl and (SCPH)Zn(II)Cl,
respectively. The proximity of the thiophene fragment to the metal ion induced
direct scalar couplings between the spin-active nucleus of the metal (111/113Cd)
and the adjacent 1H nucleus (J(CdH) = 8.97 Hz). The interaction of the metal ion
and C(21)H also was reflected by significant changes of C(21) chemical shifts:
(SCPH)Zn(II)Cl, 92.9 ppm and (SCPH)Cd(II)Cl, 88.2 ppm (free ligand (SCPH)H, 123.7
ppm). The X-ray analysis performed for (SCPH)Cd(II)Cl confirmed the side-on
cadmium-thiophene interaction. The Cd...C(21) distance (2.615(7) A) exceeded the
typical Cd-C bond lengths, but was much shorter than the corresponding van der
Waals contact. The density functional theory (DFT) was applied to model the
molecular structures of zinc(II) and cadmium(II) complexes of S-confused
thiaporphyrin. Subsequent AIM analysis demonstrated that the accumulation of
electron density between the metal and thiophene, which is necessary to induce
these couplings, was fairly small. A bond path linked the cadmium(II) ion to the
proximate C(22) carbon of the thiophene.
PMID- 17029378
TI - Porous metal-organic framework with coordinatively unsaturated Mn(II)
sites:sorption properties for various gases.
AB - A 3D porous metal-organic framework generating 1D channels, [Mn(NDC)(DEF)]n (1),
has been prepared from the solvothermal reaction of Mn(II) and 2,6
naphthalenedicarboxylic acid (H2NDC) in diethylformamide (DEF). When DEF
molecules coordinating Mn(II), which occupy the channels, are removed from 1 by
heating the crystal of 1 at 250 degrees C under vacuum for 18 h, structural
change occurs as evidenced by X-ray powder diffraction patterns. Desolvated solid
[Mn(NDC)]n (2), which contains coordinatively unsaturated Mn(II) sites, reveals
remarkable sorption capabilities for N2, H2, CO2, and CH4 gases and exhibits type
I sorption behavior indicative of permanent microporosity.
PMID- 17029379
TI - Construction of 3D layer-pillared homoligand coordination polymers from a 2D
layered precursor.
AB - Herein, we present a new method for preparing homoligand 3D coordination
polymers. First, a layered metal-organic framework Zn3(BDC)3(H2O)2 x 4DMF 1 (BDC
is terephthalate, DMF is N,N-dimethylformamide) was fabricated from a H2BDC by
liquid-liquid diffusion. Second, the layered product, 1, was used as a precursor
to solvothermally react with further H2BDC at 140-180 degrees C, resulting in two
products of BDC insertion into the layered structure. These are [Zn3(p-BDC)4] x
2HPIP, 2 (HPIP is partly protonated piperazine), and [Zn3(p-BDC)3(H2BDC)] x
(C6H15NO) x H2O x 3DMF, 3 (C6H15NO is triethylamine N-oxide). Single-crystal X
ray diffraction shows that 2 possesses a layer-pillared structure of mu4-BDC,
with 1D channels, while 3 has a layer-pillared structure of mu2-BDC, with 2D
channels. N2-sorption experiments show 3 has a relatively high BET surface area
of 750 m(2)/g. It is proposed that 2 follows the crystal growth mechanism of
Ostwald ripening, whereas the crystal structure of 3 might be formed by an
insertion mechanism.
PMID- 17029380
TI - Luminescent complexes of iridium(III) containing N/?C/?N-coordinating terdentate
ligands.
AB - A family of bis-terdentate iridium(III) complexes is reported which contain a
cyclometalated, N/?C[wedge]N-coordinating 1,3-di(2-pyridyl)benzene derivative.
This coordination mode is favored by blocking competitive cyclometalation at the
C4 and C6 positions of the ligand. Thus, 1,3-di(2-pyridyl)-4,6-dimethylbenzene
(dpyxH) reacts with IrCl3 x 3H2O to generate a dichlorobridged dimer [Ir(dpyx
N,C,N)Cl(mu-Cl)]2, 1. This dimer is cleaved by DMSO to give [Ir(dpyx)(DMSO)Cl2],
the X-ray crystal structure of which is reported here, confirming the N/?C/?N
coordination mode of dpyx. The dimer 1 can also be cleaved by a variety of other
ligands to generate novel classes of mononuclear complexes. These include charge
neutral bis-terdentate complexes of the form [Ir(N/?C/?N)(C/?N/?C)] and
[Ir(N/?C/?N)(C/?N/?O)], by reaction of 1 with C/?N/?C-coordinating ligands (e.g.,
2,6-diphenylpyridine and derivatives) and C/?N/?O-coordinating ligands (based on
6-phenylpicolinate), respectively. Treatment of 1 with terpyridines leads to
dicationic complexes of the type [Ir(N/?C/?N)(N/?N/?N)]2+, while 2-phenylpyridine
gives [Ir(dpyx-N/?C/?N)(ppy-C,N)Cl]. All of the charge-neutral complexes are
luminescent in fluid solution at room temperature. Assignment of the emission to
charge-transfer excited states with significant MLCT character is supported by
DFT calculations. In the [Ir(N/?C/?N)(C/?N/?C)] class, fluorination of the
C/?N/?C ligand at the phenyl 2' and 4' positions leads to a blue-shift in the
emission and to an increase in the quantum yield (lambda(max) = 547 nm, phi =
0.41 in degassed CH(3)CN at 295 K) compared to the nonfluorinated parent complex
(lambda(max) = 585 nm, phi = 0.21), as well as to a stabilization of the compound
with respect to photodissociation through cleavage of mutually trans Ir-C bonds.
[Ir(dpyx-N/?C/?N)(ppy-C,N)Cl] is an exceptionally bright emitter: phi = 0.76,
lambda(max) = 508 nm, in CH(3)CN at 295 K. In contrast, the
[Ir(N/?C/?N)(C/?N/?O)] complexes are much less emissive, shown to be due to fast
nonradiative decay of the excited state, probably involving reversible Ir-O bond
cleavage. The [Ir(N/?C/?N)(N/?N/?N)]2+ complexes are very feeble emitters even at
77 K, probably due to the almost exclusively interligand charge-transfer nature
of the lowest-energy excited state in these complexes.
PMID- 17029381
TI - Experimental and theoretical study of the coordination of 1,2,4-triazolato,
tetrazolato, and pentazolato ligands to the [K(18-crown-6)]+ fragment.
AB - Treatment of 3,5-diisopropyltriazole, 3,5-diphenyltriazole, 3,5-di-3
pyridyltriazole, phenyltetrazole, pyrrolidinyltetrazole, or tert-butyltetrazole
with equimolar quantities of potassium hydride and 18-crown-6 in tetrahydrofuran
at ambient temperature led to slow hydrogen evolution and formation of (3,5
diisopropyl-1,2,4-triazolato)(18-crown-6)potassium (88%), (3,5-diphenyl-1,2,4
triazolato)(tetrahydrofuran)(18-crown-6)potassium (87%), (3,5-di-3-pyridyl-1,2,4
triazolato)(18-crown-6)potassium (81%), (phenyltetrazolato)(18-crown-6)potassium
(94%), (pyrrolidinyltetrazolato)(18-crown-6)potassium (90%), and (tert
butyltetrazolato)(18-crown-6)potassium (94%) as colorless crystalline solids.
(1,2,4-Triazolato)(18-crown-6)potassium was isolated as a hemi-hydrate in 81%
yield upon treatment of 1,2,4-triazole with potassium metal in tetrahydrofuran.
The X-ray crystal structures of these new complexes were determined, and the
solid-state structures consist of the nitrogen heterocycles bonded to the (18
crown-6)potassium cationic fragments with eta2-bonding interactions. In addition,
(3,5-diphenyl-1,2,4-triazolato)(tetrahydrofuran)(18-crown-6)potassium has one
coordinated tetrahydrofuran ligand on the same face as the 3,5-diphenyl-1,2,4
triazolato ligand, while (3,5-di-3-pyridyl-1,2,4-triazolato)(18-crown-6)potassium
forms a polymeric solid through coordination of the distal 3-pyridyl nitrogen
atoms to the potassium ion on the face opposite the 1,2,4-triazolato ligand. The
solid-state structures of the new complexes show variable asymmetry in the
potassium-nitrogen distances within the eta2-interactions and also show variable
bending of the heterocyclic C2N3 and CN4 cores toward the best plane of the 18
crown-6 ligand oxygen atoms. Molecular orbital and natural bond order
calculations were carried out at the B3LYP/6-311G(d,p) level of theory on the
model complex, (phenyltetrazolato)(18-crown-6)potassium, and demonstrate that the
asymmetric potassium-nitrogen distances and bending of the CN4 core toward the 18
crown-6 ligand are due to hydrogen bond-like interactions between filled nitrogen
based orbitals and carbon-hydrogen sigma orbitals on the 18-crown-6 ligands.
Calculations carried out on the model pentazolato complex (pentazolato)(18-crown
6)potassium predict a structure in which the pentazolato ligand N5 core is bent
by 45 degrees toward the best plane of the 18-crown-6 oxygen atoms. Such bending
is induced by the formation of intramolecular nitrogen-hydrogen-carbon hydrogen
bonds. Examination of the solid-state structures of the new complexes reveals
many intramolecular and intermolecular nitrogen-hydrogen distances of < or =3.0 A
which support the presence of nitrogen-hydrogen-carbon hydrogen bonds.
PMID- 17029382
TI - Homoleptic zinc(II) complexes with first and second coordination shells of 5-tert
butylpyrazole.
AB - Reaction of hydrated Zn[NO3]2 or Zn[BF4]2 with four or more equivalents of 3{5}
tert-butylpyrazole (L(tBu)) yields [Zn(L(tBu))4]X2 (X- = NO3- or BF4-). The
nitrate complex contains C2-symmetric four-coordinate zinc(II) centers with a
slightly flattened tetrahedral geometry, and each nitrate anion hydrogen bonds to
two pyrazole N-H groups. Similar reactions with Zn[ClO4]2 or ZnCl2 in the
presence of 2 equiv of AgPF6 or AgSbF6 yield instead
[{Zn(L(tBu))4}(L(tBu))4][ClO4]2 and [{Zn(L(tBu))4}(L(tBu))2]Y2 (Y- = PF6- or SbF6
). Crystals of [{Zn(L(tBu))4}(L(tBu))4][ClO4]2 are composed of discrete
[{Zn(L(tBu))4}(L(tBu))4]2+ supramolecules that are formed from N-H...N hydrogen
bonding between zinc-bound and uncoordinated pyrazole rings. The
[{Zn(L(tBu))4}(L(tBu))4]2+ moieties are linked into planar 4(4) nets by hydrogen
bonding to bridging ClO4- anions. The ClO4- ions are almost perfectly
encapsulated in near-spherical cavities of approximate dimensions 5.0 x 5.0 x 4.5
A that are formed by two interlocked supramolecular dications. Similarly,
[{Zn(L(tBu))4}(L(tBu))2][PF6]2 crystallizes as discrete supramolecules in the
crystal with the PF6- anions occupying a shallow bowl-shaped cavity on the
surface of the complex that is formed by two zinc-bound and one uncoordinated
pyrazole ligands. (1)H NMR and IR studies of [{Zn(L(tBu))4}(L(tBu))4][ClO4]2 in
CD2Cl2 imply that the second-sphere L(tBu) ligands dissociate from the
[Zn(L(tBu))4]2+ center in this solvent and that free and metal-bound L(tBu) are
in rapid chemical exchange.
PMID- 17029383
TI - Pyridine- and phosphonate-containing ligands for stable Ln complexation.
Extremely fast water exchange on the Gd(III) chelates.
AB - Two novel ligands containing pyridine units and phosphonate pendant arms, with
ethane-1,2-diamine (L2) or cyclohexane-1,2-diamine (L3) backbones, have been
synthesized for Ln complexation. The hydration numbers obtained from luminescence
lifetime measurements in aqueous solutions of the Eu(III) and Tb(III) complexes
are q = 0.6 (EuL2), 0.7 (TbL2), 0.8 (EuL3), and 0.4 (TbL3). To further assess the
hydration equilibrium, we have performed a variable-temperature and -pressure UV
vis spectrophotometric study on the Eu(III) complexes. The reaction enthalpy,
entropy, and volume for the hydration equilibrium EuL <--> EuL(H2O) were
calculated to be DeltaH degrees = -(11.6 +/- 2) kJ mol(-1), DeltaS degrees =
(34.2 +/- 5) J mol(-1) K(-1), and = 1.8 +/- 0.3 for EuL2 and DeltaH degrees =
(13.5 +/- 1) kJ mol(-1), DeltaS degrees = -(41 +/- 4) J mol(-1) K(-1), and = 1.7
+/- 0.3 for EuL3, respectively. We have carried out variable-temperature 17O NMR
and nuclear magnetic relaxation dispersion (NMRD) measurements on the GdL2(H2O)q
and GdL3(H2O)q systems. Given the presence of phosphonate groups in the ligand
backbone, a second-sphere relaxation mechanism has been included for the analysis
of the longitudinal (17)O and (1)H NMR relaxation rates. The water exchange rate
on GdL2(H2O)q, = (7.0 +/- 0.8) x 10(8) s(-1), is extremely high and comparable to
that on the Gd(III) aqua ion, while it is slightly reduced for GdL3(H2O)q, = (1.5
+/- 0.1) x 10(8) s(-1). This fast exchange can be rationalized in terms of a very
flexible inner coordination sphere, which is slightly rigidified for L3 by the
introduction of the cyclohexyl group on the amine backbone. The water exchange
proceeds via a dissociative interchange mechanism, evidenced by the positive
activation volumes obtained from variable-pressure 17O NMR for both GdL2(H2O)q
and GdL3(H2O)q (DeltaV = +8.3 +/- 1.0 and 8.7 +/- 1.0 cm(3) mol(-1),
respectively).
PMID- 17029384
TI - Theoretical insight into electronic structures and spectroscopic properties of
[Pt2(pop)4]4-, [Pt2(pcp)4]4-, and related derivatives (pop = P2O5H2(2-) and pcp =
P2O4CH4(2-)).
AB - The structures of [Pt2(pop)4]4-, [Pt2(pcp)4]4-, and related species
[Pt2(pop)4X2]4- and [Pt2(pop)4]2- in the ground states (pop = P2O5H2(2-), pcp =
P2O4CH4(2-), and X = I, Br, and Cl) were optimized using the second-order Moller
Plesset perturbation (MP2) method. It is shown that the Pt-Pt distances decrease
in going from [Pt2(pop)4]4- to [Pt2(pop)4X2]4- to [Pt2(pop)4]2-. This is
supported by the analyses of their electronic structures. The calculated aqueous
absorption spectra at the time-dependent density functional theory (TD-DFT) level
agree with experimental observations. The unrestricted MP2 method was employed to
optimize the structures of [Pt2(pop)4]4- and [Pt2(pcp)4]4- in the lowest-energy
triplet excited states. The Pt-Pt contraction trend is well reproduced in these
calculations. For [Pt2(pop)4]4-, the Pt-Pt distance decreases from 2.905 A in the
ground state to 2.747 A in the excited state, which is comparable to experimental
values of 2.91-2.92 A and 2.64-2.71 A, respectively. On the basis of the excited
state structures of such complexes, TD-DFT predicts the solution emissions at 480
and 496 nm, which is closer to the experimental values of 512 and 510 nm
emissions, respectively.
PMID- 17029385
TI - Reversible cation/anion extraction from K2La2Ti3O10: formation of new layered
titanates, KLa2Ti3O9.5 and La2Ti3O9.
AB - A new soft-chemical transformation of layered perovskite oxides is described
wherein K2O is sequentially extracted from the Ruddlesden-Popper (R-P) phase,
K2La2Ti3O10 (I), yielding novel anion-deficient KLa2Ti3O(9.5) (II) and La2Ti3O9
(III). The transformation occurs in topochemical reactions of the R-P phase I
with PPh4Br and PBu4Br (Ph = phenyl; Bu = n-butyl). The mechanism involves the
elimination of KBr accompanied by decomposition of PR4+ (R = phenyl or n-butyl)
that extracts oxygen from the titanate. Analysis of the organic products of
decomposition reveals formation of Ph3PO, Ph3P, and Ph-Ph for R = phenyl, and
Bu3PO, Bu3P along with butane, butene, and octane for R = butyl. The inorganic
oxides II and III crystallize in tetragonal structures (II: P4/mmm, a = 3.8335(1)
A, c = 14.334(1) A; III: I4/mmm, a = 3.8565(2) A, c = 24.645(2) A) that are
related to the parent R-P phase. II is isotypic with the Dion-Jacobson phase,
RbSr2Nb3O10, while III is a unique layered oxide consisting of charge-neutral
La2Ti3O9 anion-deficient perovskite sheets stacked one over the other without
interlayer cations. Interestingly, both II and III convert back to the parent R-P
phase in a reaction with KNO3. While transformations of the R-P phases to other
related layered/three-dimensional perovskite oxides in ion
exchange/metathesis/dehydration/reduction reactions are known, the simultaneous
and reversible extraction of both cations and anions in the conversions
K2La2Ti3O10 right harpoon over left harpoon KLa2Ti3O9.5 right harpoon over left
harpoon La2Ti3O9 is reported here for the first time.
PMID- 17029386
TI - Synthesis, characterization, and UV-vis linear absorption of centrosymmetric pi
systems incorporating closo-dodecaborate clusters.
AB - Single- and multibranched centrosymmetric derivatives incorporating B12 clusters
[B12H11-N(H)=C(H)-C6H4-C6H4-C(H)=(H)N-B12H11]2- (3) and [1,3,5-(4-(B12H11
N(H)=C(H))-C6H4)-C6H3]3- (5) have been synthesized. Both derivatives were
characterized by multinuclear NMR and ESI-MS analyses. To the best of our
knowledge, compound 5 is the first example of a multicage derivative bearing
three B12 units. Compounds 3 and 5 are only slightly yellowish colored. The UV
vis absorption curves of 3 and 5 show intense absorption bands at 360 and 314 nm,
respectively. This result permits us to confirm the strong donor effect of the
B12 cluster. The hypsochrome effect observed for compound 5 compared to that of
compound 3 confirms the interest in multibranched derivatives for the preparation
of two-photon absorption materials active in the visible range.
PMID- 17029387
TI - A dehydrogenation mechanism of metal hydrides based on interactions between
Hdelta+ and H-.
AB - This paper describes a reaction mechanism that explains the dehydrogenation
reactions of alkali and alkaline-earth metal hydrides. These light metal
hydrides, e.g., lithium-based compounds such as LiH, LiAlH4, and LiNH2, are the
focus of intense research recently as the most promising candidate materials for
on-board hydrogen storage applications. Although several interesting and
promising reactions and materials have been reported, most of these reported
reactions and materials have been discovered by empirical means because of a
general lack of understanding of any underlying principles. This paper describes
an understanding of the dehydrogenation reactions on the basis of the interaction
between negatively charged hydrogen (H-, electron donor) and positively charged
hydrogen (Hdelta+, electron acceptor) and experimental evidence that captures and
explains many observations that have been reported to date. This reaction
mechanism can be used as a guidance for screening new material systems for
hydrogen storage.
PMID- 17029388
TI - Phosphorus-nitrogen compounds. Part 13. Syntheses, crystal structures,
spectroscopic, stereogenic, and anisochronic properties of novel spiro-ansa-spiro
, spiro-bino-spiro-, and spiro-crypta phosphazene derivatives.
AB - The condensation reactions of N2Ox (x = 2, 3) donor-type aminopodand (4) and
dibenzo-diaza-crown ethers (5, 6, and 9) with hexachlorocyclotriphosphazatriene,
N3P3Cl6, produce two kinds of partially substituted novel phosphazene
derivatives, namely, spiro-bino-spiro- (19) and spiro-crypta (21, 22, and 25)
phosphazenes. The partially substituted spiro-ansa-spiro-phosphazene (11) reacted
with pyrrolidine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD) give the
corresponding new fully substituted phosphazenes (14 and 16). Unexpectedly, the
reactions of 23 and 24 with pyrrolidine result in only geminal crypta
phosphazenes (26 and 27). The solid-state structures of 16 and 22 have been
determined by X-ray diffraction techniques. The relative inner hole-size of the
macrocycle in the radii of 22 is 1.27 A. The relationship between the exocyclic
NPN (alpha') and endocyclic (alpha) bond angles for spiro-crypta phosphazenes and
exocyclic OPN (alpha') bond angles for spiro-ansa-spiro- and spiro-bino-spiro
phosphazenes with 31P NMR chemical shifts of NPN and OPN phosphorus atoms,
respectively, have been investigated. The structures of 10, 14, 16, 19, 21, 22,
and 25-27 have also been examined by FTIR, 1H, 13C, and 31P NMR, HETCOR, MS, and
elemental analyses. The 31P NMR spectra of 10, 21, 22, and 25 indicate that the
compounds have anisochrony. In compounds 16 and 22, the spirocyclic nitrogen
atoms have pyramidal geometries resulting in stereogenic properties.
PMID- 17029390
TI - Isomerization processes on mixed ortho-metalated phosphine/succinimidato
[Rh2(P(C5CH4)Ph2)2(OC4NH4O)2] complexes. A sliding movement of the succinimidato
ligand.
AB - An improved preparation of mixed ortho-metalated phosphine/succinimidato
dirhodium(II) complexes, [Rh2(P(C5CH4)Ph2)2(OC4NH4O)2], allowed the isolation and
characterization of a new isomeric form having both imidato N donors trans to P,
1', that adds up to the two already known having both, 1, or only one, 2, of the
imidato N donors trans to the metalated C (Chart 3). The new complex, 1',
isomerizes to the thermodynamically stable complex 2 similarly to what had
already been observed for isomer 1. Stoichiometric and kineticomechanistic
studies of both isomerization processes have been carried out. The reactions have
been shown to occur via an intramolecular dissociatively activated process,
despite the involvement of the labile axial Rh2 coordination sites in the
formation of intermolecular adducts in solution that do not affect the processes.
Density functional theory calculations show two transition states with similar
energies for the isomerizations, in very good agreement with the
kineticomechanistic measurements. The calculation of the charge generation in the
two distinct transition states, TS1 and TS1', indicates an important increase in
the N negative charge from the reactants, more pronounced for TS1'. This fact
agrees very well with the acceleration observed for the processes in polar
solvents, especially for the 1' to 2 reaction, when compared that for the
reactions carried out in toluene.
PMID- 17029389
TI - Kinetics and mechanisms of chlorine dioxide and chlorite oxidations of cysteine
and glutathione.
AB - Chlorine dioxide oxidation of cysteine (CSH) is investigated under pseudo-first
order conditions (with excess CSH) in buffered aqueous solutions, p[H+] 2.7-9.5
at 25.0 degrees C. The rates of chlorine dioxide decay are first order in both
ClO2 and CSH concentrations and increase rapidly as the pH increases. The
proposed mechanism is an electron transfer from CS- to ClO2 (1.03 x 10(8) M(-1)
s(-1)) with a subsequent rapid reaction of the CS* radical and a second ClO2 to
form a cysteinyl-ClO2 adduct (CSOClO). This highly reactive adduct decays via two
pathways. In acidic solutions, it hydrolyzes to give CSO(2)H (sulfinic acid) and
HOCl, which in turn rapidly react to form CSO3H (cysteic acid) and Cl-. As the pH
increases, the (CSOClO) adduct reacts with CS- by a second pathway to form
cystine (CSSC) and chlorite ion (ClO2-). The reaction stoichiometry changes from
6 ClO2:5 CSH at low pH to 2 ClO2:10 CSH at high pH. The ClO2 oxidation of
glutathione anion (GS-) is also rapid with a second-order rate constant of 1.40 x
10(8) M(-1) s(-1). The reaction of ClO2 with CSSC is 7 orders of magnitude slower
than the corresponding reaction with cysteinyl anion (CS-) at pH 6.7. Chlorite
ion reacts with CSH; however, at p[H+] 6.7, the observed rate of this reaction is
slower than the ClO2/CSH reaction by 6 orders of magnitude. Chlorite ion oxidizes
CSH while being reduced to HOCl, which in turn reacts rapidly with CSH to form Cl
. The reaction products are CSSC and CSO3H with a pH-dependent distribution
similar to the ClO2/CSH system.
PMID- 17029391
TI - Synthesis and coordination behavior of planar-chiral ferrocene alkenylphosphines.
AB - A series of planar-chiral ferrocene alkenylphosphines, (S(p))-2
(diphenylphosphino)-1-vinylferrocene (2), (S(p))-2-(diphenylphosphino)-1-(prop-1
en-1-yl)ferrocene (3; as a mixture of Z and E isomers in ca. 5:1 ratio), and
(E,S(p))-2-(diphenylphosphino)-1-(2-phenylethen-1-yl)ferrocene ((E)-4), was
obtained by Wittig and Horner-Wadsworth-Emmons reactions from the common
precursor, (S(p))-2-(diphenylphosphino)ferrocene-1-carboxaldehyde (1).
Coordination properties of these novel ferrocene donors were studied in their
palladium(II) and tungsten(0)-carbonyl complexes. The reaction between 2 and
[{Pd(mu-Cl)(L(NC))}2] (5, L(NC) = 2-{(dimethylamino)methyl-kappaN}phenyl
kappaC(1)) gave the bridge-cleavage product [PdCl(L(NC))(2-kappaP)] (6) while the
reaction with [Pd(L(NC))(MeCN)2]ClO4 (7) yielded the cationic bis(chelate)
[Pd(L(NC))(2-eta2:kappaP)]ClO4 (8). Chelate complexes of the type [W(CO)4(L
eta2:kappaP)] (9 with L = 2; (Z/E)-10 with L = (Z/E)-3) were obtained by reacting
[W(CO)4(cod)] (cod = eta2:eta2-cycloocta-1,5-diene) with the appropriate
phosphinoalkene in refluxing toluene while a similar reaction with (E)-4 yielded
mixtures of [W(CO)5(4-kappaP)] ((E)-11) and [W(CO)4(4-eta2:kappaP)] ((E)-12). All
compounds were characterized by spectral methods (multinuclear NMR, IR, MS, and
CD), and the structures of 1, 2, 8, 9, (Z/E)-10, and (E)-11 were corroborated by
X-ray diffraction analysis. Ligands 2 and (E)-4 as well as their complexes 6, 8,
9, (E)-11, and (E)-12 were further studied by electrochemical methods.
PMID- 17029392
TI - Mononitrosyl tris(thiolate) iron complex [Fe(NO)(SPh)3]- and dinitrosyl iron
complex [(EtS)2Fe(NO)2]-: formation pathway of dinitrosyl iron complexes (DNICs)
from nitrosylation of biomimetic rubredoxin [Fe(SR)4]2-/1- (R = Ph, Et).
AB - Nitrosylation of the biomimetic reduced- and oxidized-form rubredoxin [Fe(SR)4]2
/1- (R = Ph, Et) in a 1:1 stoichiometry led to the formation of the extremely air
and light-sensitive mononitrosyl tris(thiolate) iron complexes (MNICs)
[Fe(NO)(SR)3]- along with byproducts [SR]- or (RS)2. Transformation of
[Fe(NO)(SR)3]- into dinitrosyl iron complexes (DNICs) [(RS)2Fe(NO)2]- and
Roussin's red ester [Fe2(mu-SR)2(NO)4] occurs rapidly under addition of 1 equiv
of NO(g) and [NO]+, respectively. Obviously, the mononitrosyl tris(thiolate)
complex [Fe(NO)(SR)3]- acts as an intermediate when the biomimetic oxidized- and
reduced-form rubredoxin [Fe(SR)4]2-/1- exposed to NO(g) were modified to form
dinitrosyl iron complexes [(RS)2Fe(NO)2]-. Presumably, NO binding to the electron
deficient [Fe(III)(SR)4]- and [Fe(III)(NO)(SR)3]- complexes triggers reductive
elimination of dialkyl/diphenyl disulfide, while binding of NO radical to the
reduced-form [Fe(II)(SR)4]2- induces the thiolate-ligand elimination. Protonation
of [Fe(NO)(SEt)3]- yielding [Fe(NO)(SPh)3]- by adding 3 equiv of thiophenol and
transformation of [Fe(NO)(SPh)3]- to [Fe(NO)(SEt)3]- in the presence of 3 equiv
of [SEt]-, respectively, demonstrated that complexes [Fe(NO)(SPh)3]- and
[Fe(NO)(SEt)3]- are chemically interconvertible. Mononitrosyl tris(thiolate) iron
complex [Fe(NO)(SPh)3]- and dinitrosyl iron complex [(EtS)2Fe(NO)2]- were
isolated and characterized by X-ray diffraction. The mean NO bond distances of
1.181(7) A (or 1.191(7) A) in complex [(EtS)2Fe(NO)2]- are nearly at the upper
end of the 1.178(3)-1.160(6) A for the anionic {Fe(NO)2}9 DNICs, while the mean
FeN(O) distances of 1.674(6) A (or 1.679(6) A) exactly fall in the range of
1.695(3)-1.661(4) A for the anionic {Fe(NO)2}9 DNICs.
PMID- 17029393
TI - Aluminumoxyhydride: improved synthesis and application as a selective reducing
agent.
AB - Aluminumoxyhydride (HAlO) has been obtained by the reaction of aluminum hydride
with the siloxane (Me2HSi)2O or the stannoxane (Bu3Sn)2O as an amorphous
colorless insoluble powder. The highest-purity product resulted from the reaction
of H3Al.NMe3 with (Me2HSi)2O. However, HAlO suspensions in tetrahydrofuran (THF)
of sufficient quality for synthetic applications can be prepared from
commercially available reagents with only minor precautions. A LiAlH4 solution in
THF was treated successively with Me3SiCl and (Me2HSi)2O, followed by heating at
60 degrees C for 20 h. The resulting suspensions are 0.4-0.5 M in active hydride
content and selectively reduce aldehydes and ketones to the respective alcohols
in the presence of any other common nonprotic functional group.
PMID- 17029395
TI - On the seeding and oligomerization of pGlu-amyloid peptides (in vitro).
AB - Oligomerization of amyloid beta (Abeta) peptides is the decisive event in the
development of Alzheimer's disease (AD), the most common neurogenerative disorder
in developed countries. Recent evidence links this conformation-driven process to
primary- and secondary-structure modifications of Abeta. The N and C terminus of
deposited Abeta has been shown to possess conspicuous heterogeneity. While the C
terminally longer form of Abeta, i.e., Abeta (42), is considered more
amyloidogenic, the role of the N-terminal modifications, e.g., truncation and
glutamate cyclization accounting for the majority of the deposited peptides, is
less understood. In the present study, we characterized the oligomerization and
seeding capacity of pGlu-amyloid peptides using two unrelated techniques based on
flow cytometry or flourescence dye binding. Under different conditions and
irrespective of the C terminus of Abeta, i.e., Abeta40 or 42, pGlu-modified
peptides displayed an up to 250-fold accelerated initial formation of aggregates
compared to unmodified Abeta. The accelerated seed formation is accompanied by a
change in the oligomerization kinetics because of N-terminal pGlu formation.
Furthermore, the formation of mixed aggregates consisting of either pGlu-Abeta (3
42) or ADan or ABri and Abeta (1-42) was investigated by Abeta fluorescence
labeling in flow cytometry. The results suggest that pGlu-modified peptides are
potential seeding species of aggregate formation in vivo. The data presented here
and the abundance of pGlu peptides in amyloidoses, such as FBD and AD, suggest
pGlu-amyloid peptides as a species with biophysical characteristics that might be
in particular crucial for the initiation of the disease.
PMID- 17029396
TI - Spinning disk confocal microscopy of live, intraerythrocytic malarial parasites.
1. Quantification of hemozoin development for drug sensitive versus resistant
malaria.
AB - We have customized a Nipkow spinning disk confocal microscope (SDCM) to acquire
three-dimensional (3D) versus time data for live, intraerythrocytic malarial
parasites. Since live parasites wiggle within red blood cells, conventional laser
scanning confocal microscopy produces blurred 3D images after reconstruction of z
stack data. In contrast, since SDCM data sets at high x, y, and z resolution can
be acquired in hundreds of milliseconds, key aspects of live parasite cellular
biochemistry can be much better resolved on physiologically meaningful times
scales. In this paper, we present the first 3D DIC transmittance "z stack" images
of live malarial parasites and use those to quantify hemozoin (Hz) produced
within the living parasite digestive vacuole, under physiologic conditions. Using
live synchronized cultures and voxel analysis of sharpened DIC z stacks, we
present the first quantitative in vivo analysis of the rate of Hz growth for
chloroquine sensitive (CQS) versus resistant (CQR) malarial parasites. We present
data for laboratory strains, as well as pfcrt transfectants expressing a CQR
conferring mutant pfcrt gene. We also analyze the rate of Hz growth in the
presence and absence of physiologically relevant doses of chloroquine (CQ) and
verapamil (VPL) and thereby present the first in vivo quantification of key
predictions from the well-known Fitch hypothesis for CQ pharmacology. In the
following paper [Gligorijevic, B., et al. (2006) Biochemistry 45, pp 12411
12423], we acquire fluorescent images of live parasite DV via SDCM and use those
to quantify DV volume for CQS versus CQR parasites.
PMID- 17029397
TI - Spinning disk confocal microscopy of live, intraerythrocytic malarial parasites.
2. Altered vacuolar volume regulation in drug resistant malaria.
AB - In the previous paper [Gligorijevic, B., et al. (2006) Biochemistry 45, pp 12400
12410], we reported on a customized Nipkow spinning disk confocal microscopy
(SDCM) system and its initial application to DIC imaging of hemozoin within live,
synchronized, intraerythrocytic Plasmodium falciparum malarial parasites. In this
paper, we probe the biogenesis as well as the volume and pH regulation of the
parasite digestive vacuole (DV), using the fluorescence imaging capabilities of
the system. Several previous reports have suggested that mutant PfCRT protein,
which causes chloroquine resistance (CQR) in P. falciparum, also causes increased
acidification of the DV. Since pH and volume regulation are often linked, we
wondered whether DV volume differences might be associated with CQR. Using fast
acquisition of SDCM z stacks for synchronized parasites with OGd internalized
into the DV, followed by iterative deconvolution using experimental point spread
functions, we quantify the volume of the DV for live, intraerythrocytic HB3
(CQS), Dd2 (CQR via drug selection), GCO3 (CQS), and GCO3/C3(Dd2) (CQR via
transfection with mutant pfcrt) malarial parasites as they develop within the
human red blood cell. We find that relative to both CQS strains, both CQR strains
show significantly increased DV volume as the organelle forms upon entry into the
trophozoite stage of development and that this persists until the trophozoite
schizont boundary. A more acidic DV pH is found for CQR parasites as soon as the
organelle forms and persists throughout the trophozoite stage. We probe DV volume
and pH changes upon ATP depletion, hypo- and hypertonic shock, and rapid
withdrawal of perfusate chloride. Taken together, these data suggest that the
PfCRT mutations that cause CQR also lead to altered DV volume regulation.
PMID- 17029399
TI - Isoform-specific membrane insertion of secretory phospholipase A2 and functional
implications.
AB - Despite increasing evidence that the membrane-binding mode of interfacial enzymes
including the depth of membrane insertion is crucial for their function, the
membrane insertion of phospholipase A(2) (PLA(2)) enzymes has not been studied
systematically. Here, we analyze the membrane insertion of human group IB PLA(2)
(hIBPLA(2)) and compare it with that of a structurally homologous V3W mutant of
human group IIA PLA(2) (V3W-hIIAPLA(2)) and with a structurally divergent group
III bee venom PLA(2) (bvPLA(2)). Increasing the anionic charge of membranes
results in a blue shift of the fluorescence of Trp(3) of hIBPLA(2), a decrease in
quenching by acrylamide, and an increase in enzyme activity, reflecting an
enhancement in the membrane binding of PLA(2). Fluorescence quenching by
brominated lipids indicates significant penetration of Trp(3) into fluid
POPC/POPG membranes but little insertion into the solid DPPC/DPPG membranes.
Increased membrane fluidity also supports hIBPLA(2) activity, suggesting that
membrane insertion of hIBPLA(2) is controlled by membrane fluidity and is
necessary for the full activity of the enzyme. Trp fluorescence quenching of the
V3W-hIIAPLA(2) and bvPLA(2) by water- and membrane-soluble quenchers indicates
substantial membrane insertion of Trp(3) of V3W-hIIAPLA(2), similar to that found
for hIBPLA(2), and no insertion of tryptophans of bvPLA(2). Our results provide
evidence that (a) structurally similar group IB and IIA PLA(2)s, but not
structurally diverse group III PLA(2), significantly penetrate into membranes;
(b) membrane insertion is controlled by membrane fluidity and facilitates
activation of IB and IIA PLA(2)s; and (c) structurally distinct PLA(2) isoforms
may employ different tactics of substrate accession/product release during lipid
hydrolysis.
PMID- 17029398
TI - Atomic force microscopy reveals DNA bending during group II intron
ribonucleoprotein particle integration into double-stranded DNA.
AB - The mobile Lactococcus lactis Ll.LtrB group II intron integrates into DNA target
sites by a mechanism in which the intron RNA reverse splices into one DNA strand
while the intron-encoded protein uses a C-terminal DNA endonuclease domain to
cleave the opposite strand and then uses the cleaved 3' end to prime reverse
transcription of the inserted intron RNA. These reactions are mediated by an RNP
particle that contains the intron-encoded protein and the excised intron lariat
RNA, with both the protein and base pairing of the intron RNA used to recognize
DNA target sequences. Here, computational analysis indicates that Escherichia
coli DNA target sequences that support Ll.LtrB integration have greater predicted
bendability than do random E. coli genomic sequences, and atomic force microscopy
shows that target DNA is bent during the reaction with Ll.LtrB RNPs. Time course
and mutational analyses show that DNA bending occurs after reverse splicing and
requires subsequent interactions between the intron-encoded protein and the 3'
exon, which lead to two progressively larger bend angles. Our results suggest a
model in which RNPs bend the target DNA by maintaining initial contacts with the
5' exon while engaging in subsequent 3' exon interactions that successively
position the scissile phosphate for bottom-strand cleavage at the DNA
endonuclease active site and then reposition the 3' end of the cleaved bottom
strand to the reverse transcriptase active site for initiation of cDNA synthesis.
Our findings indicate that bendability of the DNA target site is a significant
factor for Ll.LtrB RNP integration.
PMID- 17029400
TI - Structural and functional effects of tryptophans inserted into the membrane
binding and substrate-binding sites of human group IIA phospholipase A2.
AB - Phospholipase A(2) (PLA(2)) enzymes become activated by binding to biological
membranes and hydrolyze phospholipids to free fatty acids and lyso-phospholipids,
the precursors of inflammatory mediators. To understand the functional
significance of amino acid residues at key positions, we have studied the effects
of the substitution of Val(3) (membrane binding surface) and Phe(5) (substrate
binding pocket) of human group IIA PLA(2) by tryptophan on the structure and
function of the enzyme. Despite the close proximity of the sites of mutations,
the V3W mutation results in substantial enhancement of the enzyme activity,
whereas the F5W mutant demonstrates significantly suppressed activity. A
structural analysis of all three proteins free in buffer and bound to membranes
indicates that large differences in activities result from distinct
conformational changes in PLA(2)s upon membrane binding. Although PLA(2) and the
V3W mutant demonstrate a decrease in helical content and an increase in helix
flexibility, the F5W mutant experiences partial distortion of the alpha-helical
structure presumably resulting from the tendency of Trp(5) to insert into the
membrane. Furthermore, whereas the PLA(2) and the V3W mutant bind to the membrane
at similar and apparently productive-mode orientation, the F5W mutant binds to
membranes with a distinctly different orientation. It is suggested that both the
stimulatory effect of the V3W mutation and the inhibitory effect of the F5W
mutation result from the high affinity of Trp for the membrane-water interface.
Although Trp(3) at the membrane binding face of PLA(2) facilitates the proper
membrane binding of the enzyme, Trp(5) in the internal substrate binding site
causes partial unwinding of the N-terminal helix in order to interact with the
membrane.
PMID- 17029401
TI - Evidence for a gem-diol reaction intermediate in bacterial C-C hydrolase enzymes
BphD and MhpC from 13C NMR spectroscopy.
AB - C-C hydrolase enzymes MhpC and BphD catalyze the hydrolytic C-C cleavage of meta
ring fission intermediates on the Escherichia coli phenylpropionic acid and
Burkholderia xenovorans LB400 biphenyl degradation pathways and are both members
of the alpha/beta-hydrolase family containing a Ser-His-Asp catalytic triad. The
catalytic mechanism of this family of enzymes is thought to proceed via a gem
diol reaction intermediate, which has not been observed directly. Site-directed
single mutants of BphD in which catalytic residues His-265 and Ser-112 were
replaced with Ala were found to possess 10(4)-fold reduced k(cat) values, and in
each case, the C-C cleavage step was shown by pre-steady-state kinetic analysis
to be rate-limiting. The processing of a 6-(13)C-labeled aryl-containing
substrate by these H265A or S112A mutant BphD enzymes was monitored directly by
(13)C NMR spectroscopy. A new line-broadened signal was observed at 128 ppm for
each enzyme, corresponding to the proposed gem-diol reaction intermediate, over a
time scale of 1-24 h. A similar signal was observed upon incubation of the (13)C
labeled substrate with an H114A MhpC mutant, which is able to accept the 6-phenyl
containing substrate, on a shorter time scale. The direct observation of a gem
diol intermediate provides further evidence that supports a general base
mechanism for this family of enzymes.
PMID- 17029402
TI - Catalytic role for arginine 188 in the C-C hydrolase catalytic mechanism for
Escherichia coli MhpC and Burkholderia xenovorans LB400 BphD.
AB - The alpha/beta-hydrolase superfamily, comprised mainly of esterase and lipase
enzymes, contains a family of bacterial C-C hydrolases, including MhpC and BphD
which catalyze the hydrolytic C-C cleavage of meta-ring fission intermediates on
the Escherichia coli phenylpropionic acid pathway and Burkholderia xenovorans
LB400 biphenyl degradation pathway, respectively. Five active site amino acid
residues (Arg-188, Asn-109, Phe-173, Cys-261, and Trp-264) were identified from
sequence alignments that are conserved in C-C hydrolases, but not in enzymes of
different function. Replacement of Arg-188 in MhpC with Gln and Lys led to 200-
and 40-fold decreases, respectively, in k(cat); the same replacements for Arg-190
of BphD led to 400- and 700-fold decreases, respectively, in k(cat). Pre-steady
state kinetic analysis of the R188Q MhpC mutant revealed that the first step of
the reaction, keto-enol tautomerization, had become rate-limiting, indicating
that Arg-188 has a catalytic role in ketonization of the dienol substrate, which
we propose is via substrate destabilization. Mutation of nearby residues Phe-173
and Trp-264 to Gly gave 4-10-fold reductions in k(cat) but 10-20-fold increases
in K(m), indicating that these residues are primarily involved in substrate
binding. The X-ray structure of a succinate-H263A MhpC complex shows concerted
movements in the positions of both Phe-173 and Trp-264 that line the approach to
Arg-188. Mutation of Asn-109 to Ala and His yielded 200- and 350-fold reductions,
respectively, in k(cat) and pre-steady-state kinetic behavior similar to that of
a previous S110A mutant, indicating a role for Asn-109 is positioning the active
site loop containing Ser-110. The catalytic role of Arg-188 is rationalized by a
hydrogen bond network close to the C-1 carboxylate of the substrate, which
positions the substrate and promotes substrate ketonization, probably via
destabilization of the bound substrate.
PMID- 17029403
TI - Metal-linked dimerization in the iron-dependent regulator from Mycobacterium
tuberculosis.
AB - The iron-dependent regulator (IdeR) is a 230-amino acid transcriptional repressor
that regulates iron homeostasis, oxidative stress response and virulence in
Mycobacterium tuberculosis. The natural ligand for IdeR is Fe(II), but Ni(II),
Co(II), Cd(II), Mn(II), and Zn(II) also bind to and activate the protein in
vitro. Protein activation by metal is a complex process involving metal-induced
folding of the N-terminal domain, changes in the interaction between the N- and C
terminal domains, and the formation of homodimers. Here, we investigate the
energetics of dimerization and metal binding in IdeR. The dimerization energetics
were determined as a function of metal binding using equilibrium analytical
ultracentrifugation. The equilibrium dimer dissociation constant of apo-IdeR was
4.0 microM at 20 degrees C. The dissociation constant decreased to 0.5 microM in
the presence of one equivalent of Ni(II)Cl(2) and decreased further (K(d) << 50
nM) in the presence of excess Ni(II). IdeR contains two tryptophan residues. The
addition of Ni(II) induced changes in fluorescence intensity and emission maximum
of the tryptophan residues that strongly depended on protein concentration. At
low IdeR concentration, fluorescence was enhanced at low metal-to-protein ratios
but was quenched at high metal-to-protein ratios. At high IdeR concentration,
metal binding resulted only in fluorescence quenching. The fluorescence
enhancement at low protein concentrations was buffer-dependent and required the
presence of both tryptophans. Metal binding affinity was measured quantitatively
using equilibrium dialysis. The results showed strongly positive cooperative
binding of three equivalents of metal per monomer with an average apparent
dissociation constant of 2.2 +/- 0.3 microM and a Hill coefficient of 2. Metal
binding was not cooperative in an IdeR variant that showed reduced affinity for
dimer formation. The results of this study establish the positive cooperative
nature of metal binding by IdeR and suggest that dimerization is a major
contributor to cooperative binding. The strong coupling between metal binding and
dimerization places specific constraints on the activation mechanism.
PMID- 17029404
TI - Identification of tyrosine 79 in the tocopherol binding site of glutathione S
transferase pi.
AB - Alpha-tocopherol, the most abundant form of vitamin E present in humans, is a
noncompetitive inhibitor of glutathione S-transferase pi (GST pi), but its
binding site had not been located. Tocopherol iodoacetate (TIA), a reactive
analogue, produces a time-dependent inactivation of GST pi to a limit of 25%
residual activity. The rate constant for inactivation, k(obs), exhibits a
nonlinear dependence on reagent concentration, with K(I) = 19 microM and k(max) =
0.158 min(-)(1). Complete protection against inactivation is provided by
tocopherol and tocopherol acetate, whereas glutathione derivatives, electrophilic
substrate analogues, buffers, or nonsubstrate hydrophobic ligands have little
effect on k(obs). These results indicate that TIA reacts as an affinity label of
a distinguishable tocopherol binding site. Loss of activity occurs concomitant
with incorporation of about 1 mol of reagent/mol of enzyme subunit when the
enzyme is maximally inactivated. Isolation of the labeled peptide from the
tryptic digest shows that Tyr(79) is the only enzymic amino acid modified. The
Y79F, Y79S, and Y79A mutant enzymes were generated, expressed, and purified.
Changing Tyr(79) to Ser or Ala, but not Phe, renders the enzyme insensitive to
inhibition by either tocopherol or tocopherol acetate as demonstrated by
increases of at least 49-fold in K(I) values as compared to the wild-type enzyme.
These results and examination of the crystal structure of GST pi suggest that
tocopherols bind at a novel site, where an aromatic residue at position 79 is
essential for binding.
PMID- 17029405
TI - The endothelium-derived hyperpolarizing factor, H2O2, promotes metal-ion efflux
in aortic endothelial cells: elemental mapping by a hard X-ray microprobe.
AB - Hydrogen peroxide (H(2)O(2)) is a physiologic oxidant implicated in vascular cell
signaling, although little is known about the biochemical consequences of its
reaction with endothelial cells. Submicrometer-resolution hard X-ray elemental
mapping of cultured porcine aortic endothelial cells (PAEC) has provided data on
the global changes for intracellular elemental density within PAEC and indicates
an efflux of metal ions and phosphorus from the cytoplasm after H(2)O(2)
treatment. The synchrotron-radiation-induced X-ray emission experiments (SRIXE)
show that H(2)O(2)-treated cells are irregularly shaped and exhibit blebbing
indicative of increased permeability due to the damaged membrane. The SRIXE
results suggest that H(2)O(2)-induced damage is largely restricted to the cell
membrane as judged by the changes to membrane and cytoplasmic components rather
than the cell nucleus. The SRIXE data also provide a mechanism for cell
detoxification as the metal-ion efflux resulting from the initial H(2)O(2)
mediated changes to cell membrane potentially limits intracellular metal-mediated
redox processes through Fenton-like chemistry. They may also explain the
increased levels of these ions in atherosclerotic plaques, regardless of whether
they are involved in plaque formation. Finally, the SRIXE data support the notion
that cultured endothelial cells exposed to H(2)O(2) respond with enhanced
cellular metal-ion efflux into the extracellular space.
PMID- 17029406
TI - Dynamic behavior of fatty acid spin labels within a binding site of soybean
lipoxygenase-1.
AB - The putative substrate-binding site in lipoxygenases is long and internal. There
is little direct evidence about how the unsaturated fatty acid substrates enter
and move within the cavity to position themselves correctly for electron transfer
reactions with the catalytic non-heme iron. An EPR spectroscopy approach, with
spin-labeled fatty acids, is taken here to investigate dynamic behavior of fatty
acids bound to soybean lipoxygenase-1. The probes are labeled on C5, C8, C10,
C12, and C16 of stearic acid. The EPR-determined affinity for the enzyme
increases as the length of the alkyl end of the probe increases, with a
DeltaDeltaG of -190 cal/methylene. The probes in the series exhibit similar
enhanced paramagnetic relaxation by the iron center. These results indicate that
the members of the series have a common binding site. All of the bound probes
undergo considerable local mobility. The stearate spin-labeled at C5 has the
highest affinity for the lipoxygenase, and it is a competitive inhibitor, with a
K(i) of 9 muM. Surprisingly, this stearate labeled near the carboxyl end
undergoes more local motion than those labeled in the middle of the chain, when
it is bound. This shows that the carboxyl end of the fatty-acid spin label is not
rigidly docked on the protein. During catalysis, repositioning of the substrate
carboxyl on the protein surface may be coupled to motion of portions of the chain
undergoing reaction.
PMID- 17029408
TI - Evaluating the roles of the heme a side chains in cytochrome c oxidase using
designed heme proteins.
AB - Heme a is a redox cofactor unique to cytochrome c oxidases and vital to aerobic
respiration. Heme a differs from the more common heme b by two chemical
modifications, the C-8 formyl group and the C-2 hydroxyethylfarnesyl group. The
effects of these porphyrin substituents on ferric and ferrous heme binding and
electrochemistry were evaluated in a designed heme protein maquette. The maquette
scaffold chosen, [Delta7-H3m](2), is a four-alpha-helix bundle that contains two
bis(3-methyl-l-histidine) heme binding sites with known absolute ferric and
ferrous heme b affinities. Hemes b, o, o+16, and heme a, those involved in the
biosynthesis of heme a, were incorporated into the bis(3-methyl-l-histidine) heme
binding sites in [Delta7-H3m](2). Spectroscopic analyses indicate that 2 equiv of
each heme binds to [Delta7-H3m](2), as designed. Equilibrium binding studies of
the hemes with the maquette demonstrate the tight affinity for hemes containing
the C-2 hydroxyethylfarnesyl group in both the ferric and ferrous forms. Coupled
with the measured equilibrium midpoint potentials, the data indicate that the
hydroxyethylfarnesyl group stabilizes the binding of both ferrous and ferric heme
by at least 6.3 kcal/mol via hydrophobic interactions. The data also demonstrate
that the incorporation of the C-8 formyl substituent in heme a results in a 179
mV, or 4.1 kcal/mol, positive shift in the heme reduction potential relative to
heme o due to the destabilization of ferric heme binding relative to ferrous heme
binding. The two substituents appear to counterbalance each other to provide for
tighter heme a affinity relative to heme b in both the ferrous and ferric forms
by at least 6.3 and 2.1 kcal/mol, respectively. These results also provide a
rationale for the reaction sequence observed in the biosynthesis of heme a.
PMID- 17029407
TI - The W105G and W99G sorcin mutants demonstrate the role of the D helix in the
Ca(2+)-dependent interaction with annexin VII and the cardiac ryanodine receptor.
AB - Sorcin, a 21.6 kDa two-domain penta-EF-hand (PEF) protein, when activated by
Ca(2+) binding, interacts with target proteins in a largely uncharacterized
process. The two physiological EF-hands EF3 and EF2 do not belong to a structural
pair but are connected by the D helix. To establish whether this helix is
instrumental in sorcin activation, two D helix residues were mutated: W105,
located near EF3 and involved in a network of interactions, and W99, located near
EF2 and facing solvent, were substituted with glycine. Neither mutation alters
calcium affinity. The interaction of the W105G and W99G mutants with annexin VII
and the cardiac ryanodine receptor (RyR2), requiring the sorcin N-terminal and C
terminal domain, respectively, was studied. Surface plasmon resonance experiments
show that binding of annexin VII to W99G occurs at the same Ca(2+) concentration
as that of the wild type, whereas W105G requires a significantly higher Ca(2+)
concentration. Ca(2+) spark activity of isolated heart cells monitors the sorcin
RyR2 interaction and is unaltered by W105G but is reduced equally by W99G and the
wild type. Thus, substitution of W105, via disruption of the network of D helix
interactions, affects the capacity of sorcin to recognize and interact with
either target at physiological Ca(2+) concentrations, while mutation of solvent
facing W99 has little effect. The D helix appears to amplify the localized
structural changes that occur at EF3 upon Ca(2+) binding and thereby trigger a
structural rearrangement that enables interaction of sorcin with its molecular
targets. The same activation process may apply to other PEF proteins in view of
the D helix conservation.
PMID- 17029409
TI - Characterization of the LSGGQ and H motifs from the Escherichia coli lipid A
transporter MsbA.
AB - ATP-binding cassette (ABC) transporters make up one of the largest superfamilies
of proteins known and have been shown to transport substrates ranging from lipids
and antibiotics to sugars and amino acids. The dysfunction of ABC transporters
has been linked to human pathologies such as cystic fibrosis, hyperinsulinemia,
and macular dystrophy. Several bacterial ABC transporters are also necessary for
bacterial survival and transport of virulence factors in an infected host. MsbA
is a 65 kDa protein that forms a functional homodimer consisting of two six-helix
transmembrane domains and two approximately 250 amino acid nucleotide-binding
domains (NBD). The NBDs contain several conserved regions such as the Walker A,
LSGGQ, and H motif that bind directly to ATP and align it for hydrolysis. MsbA
transports lipid A, its native substrate, across the inner membrane of Gram
negative bacteria. The loss or dysfunction of MsbA results in a toxic
accumulation of lipid A inside the cell, leading to cell-membrane instability and
cell death. Using site-directed spin labeling electron paramagnetic resonance
spectroscopy, conserved motifs within the MsbA NBD have been evaluated for
structure and dynamics upon substrate binding. It has been determined that the
LSGGQ NBD consensus sequence is consistent with an alpha-helical conformation and
that these residues maintain extensive tertiary contacts throughout hydrolysis.
The dynamics of the LSGGQ and the H-motif region have been studied in the
presence of ATP, ADP, and ATP plus vanadate to identify the residues that are
directly affected by interactions with the substrate before, after, and during
hydrolysis, respectively.
PMID- 17029411
TI - Structural impact of heparin binding to full-length Tau as studied by NMR
spectroscopy.
AB - The neuronal Tau protein is involved in stabilizing microtubules but is also the
major component of the paired helical filaments (PHFs), the intracellular
aggregates that characterize Alzheimer's disease (AD) in neurons. In vitro, Tau
can be induced to form AD-like aggregates by adding polyanions such as heparin.
While previous studies have identified the microtubule binding repeats (MTBRs) as
the major player in Tau aggregation, the fact that the full-length protein does
not aggregate by itself indicates the presence of inhibitory factors. Charge and
conformational changes are of uttermost importance near the second (R2) and third
(R3) MTBR that are thought to be involved directly in the nucleation of the
aggregation. Recently, the positively charged regions flanking the MTBR were
proposed to inhibit PHF assembly, where hyperphosphorylation neutralizes these
basic inhibitory domains, enabling Tau-Tau interactions. Here we present results
of an NMR study on the interaction between intact full-length Tau and small
heparin fragments of well-defined size, under conditions where no aggregation
occurs. Our findings reveal (i) micromolar affinity of heparin to residues in R2
and R3, (ii) two zones of strong interaction within the positively charged
inhibitory regions flanking the MTBR, and (iii) another interaction site upstream
of the two inserts encoded by exons 2 and 3. Three-dimensional heteronuclear NMR
experiments demonstrate that the interaction with heparin induces beta-strand
structure in several regions of Tau that might act as nucleation sites for its
aggregation but indicate as well alpha-helical structure in regions outside the
core of PHF. In the PHF, the residues outside of the core maintain sufficient
mobility for NMR detection and recover their unbound chemical shift values after
an overnight incubation at 37 degrees C with heparin. Heparin thus becomes
integrated into the rigid core region of the PHF, probably providing the charge
compensation for the lysine-rich stretches that form upon the in-register,
parallel stacking of the repeat regions.
PMID- 17029412
TI - Mechanism of the conformational transitions in 6-hydroxymethyl-7,8-dihydropterin
pyrophosphokinase as revealed by NMR spectroscopy.
AB - 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer
of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), leading to
the biosynthesis of folate cofactors. HPPK undergoes dramatic conformational
changes during its catalytic cycle, and the conformational changes are essential
for enzymatic catalysis. Thus, the enzyme is not only an attractive target for
developing antimicrobial agents but also an excellent model system for studying
the catalytic mechanism of enzymatic pyrophosphoryl transfer as well as the role
of protein dynamics in enzymatic catalysis. In the present study, we report the
NMR solution structures of the binary complex HPPK*MgAMPCPP and the ternary
complex HPPK*MgAMPCPP*DMHP, where alpha,beta-methyleneadenosine triphosphate
(AMPCPP) and 7, 7-dimethyl-6-hydroxypterin (DMHP) are the analogues of the
substrates ATP and HP, respectively. The results suggest that the three catalytic
loops of the binary complex of HPPK can assume multiple conformations in slow
exchanges as evidenced by multiple sets of NMR signals for several residues in
loops 2 and 3 and the very weak or missing NH cross-peaks for several residues in
loops 1 and 3. However, the ternary complex shows only one set of NMR signals,
and the cross-peak intensities are rather uniform, suggesting that the binding of
the second substrate shifts the multiple conformations of the binary complex to
an apparently single conformation of the ternary complex. The NMR behaviors and
conformations of the binary complex HPPK*MgAMPCPP are significantly different
from those of HPPK in complex with Mgbeta,gamma-methyleneadenosine triphosphate
(MgAMPPCP). It is suggested that the conformational properties of the binary
substrate complex HPPK*MgATP be represented by those of HPPK*MgAMPCPP, because
MgAMPCPP is a better MgATP analogue for HPPK with respect to both binding
affinity and bound conformation.
PMID- 17029410
TI - Rational design of new binding specificity by simultaneous mutagenesis of
calmodulin and a target peptide.
AB - Calcium-saturated calmodulin (CaM) binds and influences the activity of a varied
collection of target proteins in most cells. This promiscuity underlies the role
of CaM as a shared participant in calcium-dependent signal transduction pathways
but imposes a handicap on popular CaM-based calcium biosensors, which display an
undesired tendency to cross-react with cellular proteins. Designed CaM/target
pairs that retain high affinity for one another but lack affinity for wild-type
CaM and its natural interaction partners would therefore be useful as sensor
components and possibly also as elements of "synthetic" cellular-signaling
networks. Here, we have adopted a rational approach to creating suitably modified
CaM/target complexes by using computational design methods to guide parallel site
directed mutagenesis of both binding partners. A hierarchical design procedure
was applied to suggest a small number of complementary mutations on CaM and on a
peptide ligand derived from skeletal-muscle light-chain kinase (M13).
Experimental analysis showed that the procedure was successful in identifying CaM
and M13 mutants with novel specificity for one another. Importantly, the designed
complexes retained an affinity comparable to the wild-type CaM/M13 complex. These
results represent a step toward the creation of CaM and M13 derivatives with
specificity fully orthogonal to the wild-type proteins and show that
qualitatively accurate predictions may be obtained from computational methods
applied simultaneously to two proteins involved in multiple-linked binding
equilibria.
PMID- 17029413
TI - Alternatively spliced exon B of myosin Va is essential for binding the tail
associated light chain shared by dynein.
AB - A 10 kDa dynein light chain (DLC), previously identified as a tail light chain of
myosin Va, may function as a cargo-binding and/or regulatory subunit of both
myosin and dynein. Here, we identify and characterize the binding site of DLC on
myosin Va. Fragments of the human myosin Va tail and the DLC2 isoform were
expressed, and their complex formation was analyzed by pull-down assays, gel
filtration, and spectroscopic methods. DLC2 was found to bind as a homodimer to a
approximately 15 residue segment (Ile1280-Ile1294) localized between the medial
and distal coiled-coil domains of the tail. The binding region contains the three
residues coded by the alternatively spliced exon B (Asp1284-Lys1286). Removal of
exon B eliminates DLC2 binding. Co-localization experiments in a transfected
mammalian cell line confirm our finding that exon B is essential for DLC2
binding. Using circular dichroism, we demonstrate that binding of DLC2 to a
approximately 85 residue disordered domain (Pro1235-Arg1320) induces some helical
structure and stabilizes both flanking coiled-coil domains (melting temperature
increases by approximately 7 degrees C). This result shows that DLC2 promotes the
assembly of the coiled-coil domains of myosin Va. Nuclear magnetic resonance
spectroscopy and docking simulations show that a 15 residue peptide (Ile1280
Ile1294) binds to the surface grooves on DLC2 similarly to other known binding
partners of DLCs. When our data are taken together, they suggest that exon B and
its associated DLC2 have a significant effect on the structure of parts of the
coiled-coil tail domains and such a way could influence the regulation and cargo
binding function of myosin Va.
PMID- 17029414
TI - Role of Asp1393 in catalysis, flavin reduction, NADP(H) binding, FAD
thermodynamics, and regulation of the nNOS flavoprotein.
AB - Nitric oxide synthases (NOS) are flavoheme enzymes with important roles in
biology. The reductase domain of neuronal NOS (nNOSr) contains a widely conserved
acidic residue (Asp(1393)) that is thought to facilitate hydride transfer between
NADPH and FAD. Previously we found that the D1393V and D1393N mutations lowered
the NO synthesis activity and the rates of heme and flavin reduction in full
length nNOS. To examine the mechanisms for these results in greater detail, we
incorporated D1393V and D1393N substitutions into nNOSr along with a truncated
NADPH-FAD domain construct (FNR) and characterized the mutants. D1393V nNOSr had
markedly lower (H2+H and its isotopomers; (2) the
H+RH-->H2+R reactions, where RH is an alkane, beginning with H+CH4-->H2+CH3 and
extending to much larger alkanes; and (3) the Cl+RH-->HCl+R reactions,
principally Cl+CH4-->HCl+CH3. We describe the experiments, discuss their results,
present comparisons with theory, and introduce heuristic models.
PMID- 17029424
TI - Including quantum effects in the dynamics of complex (i.e., large) molecular
systems.
AB - The development in the 1950s and 1960s of crossed molecular beam methods for
studying chemical reactions at the single-collision molecular level stimulated
the need and desire for theoretical methods to describe these and other dynamical
processes in molecular systems. Chemical dynamics theory has made great strides
in the ensuing decades, so that methods are now available for treating the
quantum dynamics of small molecular systems essentially completely. For the large
molecular systems that are of so much interest nowadays (e.g., chemical reactions
in solution, in clusters, in nanostructures, in biological systems, etc.),
however, the only generally available theoretical approach is classical molecular
dynamics (MD) simulations. Much effort is currently being devoted to the
development of approaches for describing the quantum dynamics of these complex
systems. This paper reviews some of these approaches, especially the use of
semiclassical approximations for adding quantum effects to classical MD
simulations, also showing some new versions that should make these semiclassical
approaches even more practical and accurate.
PMID- 17029425
TI - The study of state-selected ion-molecule reactions using the vacuum ultraviolet
pulsed field ionization-photoion technique.
AB - This paper presents the methodology to generate beams of ions in single quantum
states for bimolecular ion-molecule reaction dynamics studies using pulsed field
ionization (PFI) of atoms or molecules in high-n Rydberg states produced by
vacuum ultraviolet (VUV) synchrotron or laser photoexcitation. Employing the
pseudocontinuum high-resolution VUV synchrotron radiation at the Advanced Light
Source as the photoionization source, PFI photoions (PFI-PIs) in selected
rovibrational states have been generated for ion-molecule reaction studies using
a fast-ion gate to pass the PFI-PIs at a fixed delay with respect to the
detection of the PFI photoelectrons (PFI-PEs). The fast ion gate provided by a
novel interleaved comb wire gate lens is the key for achieving the optimal signal
to-noise ratio in state-selected ion-molecule collision studies using the VUV
synchrotron based PFI-PE secondary ion coincidence (PFI-PESICO) method. The most
recent development of the VUV laser PFI-PI scheme for state-selected ion-molecule
collision studies is also described. Absolute integral cross sections for state
selected H2+ ions ranging from v+ = 0 to 17 in collisions with Ar, Ne, and He at
controlled translational energies have been obtained by employing the VUV
synchrotron based PFI-PESICO scheme. The comparison between PFI-PESICO cross
sections for the H2+(HD+)+Ne and H2+(HD+)+He proton-transfer reactions and
theoretical cross sections based on quasiclassical trajectory (QCT) calculations
and three-dimensional quantum scattering calculations performed on the most
recently available ab initio potential energy surfaces is highlighted. In both
reaction systems, quantum scattering resonances enhance the integral cross
sections significantly above QCT predictions at low translational and vibrational
energies. At higher energies, the agreement between experiment and quasiclassical
theory is very good. The profile and magnitude of the kinetic energy dependence
of the absolute integral cross sections for the H2+(v+ = 0-2,N+ = 1)+He proton
transfer reaction unambiguously show that the inclusion of Coriolis coupling is
important in quantum dynamics scattering calculations of ion-molecule collisions.
PMID- 17029426
TI - Recent advances in crossed-beam studies of bimolecular reactions.
AB - A critical overview of the recent progress in crossed-beam reactive scattering is
presented. This review is not intended to be an exhaustive nor a comprehensive
one, but rather a critical assessment of what we have been learning about
bimolecular reaction dynamics using crossed molecular beams since year 2000.
Particular emphasis is placed on the information content encoded in the product
angular distribution-the trait of a typical molecular beam scattering experiment
and how the information can help in answering fundamental questions about
chemical reactivity. We will start with simple reactions by highlighting a few
benchmark three-atom reactions, and then move on progressively to the more
complex chemical systems and with more sophisticated types of measurements.
Understanding what cause the experimental observations is more than
computationally simulating the results. The give and take between experiment and
theory in unraveling the physical picture of the underlying dynamics is
illustrated throughout this review.
PMID- 17029427
TI - Mode- and bond-selective reaction of Cl(2P3/2) with CH3D: C-H stretch overtone
excitation near 6000 cm(-1).
AB - Experiments explore the influence of different C-H stretching eigenstates of CH3D
on the reaction of CH3D with Cl(2P3/2). We prepare the mid |110>|0>(A1,E), mid
|200>|>0(E), and mid |100>|0> +nu3 +nu5 eigenstates by direct midinfrared
absorption near 6000 cm(-1). The vibrationally excited molecules react with
photolytic Cl atoms, and we monitor the vibrational states of the CH2D or CH3
radical products by 2+1 resonance enhanced multiphoton ionization. Initial
excitation of the |200>|0>(E) state leads to a twofold increase in CH2D products
in the vibrational ground state compared to|100>|0> +nu3 +nu5 excitation,
indicating mode-selective chemistry in which the C-H stretch motion couples more
effectively to the H-atom abstraction coordinate than bend motion. For two
eigenstates that differ only in the symmetry of the vibrational wave function,
|110>|0>(A1) and |110>|0>(E), the ratio of reaction cross sections is 1.00 +/-
0.05, showing that there is no difference in enhancement of the H-atom
abstraction reaction. Molecules with excited local modes corresponding to one
quantum of C-H stretch in each of two distinct oscillators react exclusively to
form C-H stretch excited CH2D products. Conversely, eigenstates containing
stretch excitation in a single C-H oscillator form predominantly ground
vibrational state CH2D products. Analyzing the product state yields for reaction
of the |110>|0>(A1) state of CH3D yields an enhancement of 20 +/- 4 over the
thermal reaction. A local mode description of the vibrational motion along with a
spectator model for the reactivity accounts for all of the observed dynamics.
PMID- 17029428
TI - State-to-state quantum reactive scattering for four-atom chemical reactions:
differential cross section for the H+H2O-->H2+OH abstraction reaction.
AB - The time-dependent wave packet method was extended to calculate the state-to
state differential cross section for the title four-atom abstraction reaction
with H2O in the ground rovibrational state. One spectator OH bond length was
fixed in the study, but the remaining five degrees of freedom were treated
exactly. It was found that (a) the differential cross section changes from being
strongly backward peaked at low collision energy to sideward scattering at E =
1.4 eV, and (b) the rotational state-resolved differential cross section for H2
differs substantially from that for OH.
PMID- 17029429
TI - A crossed molecular beam study on the dynamics of F atom reaction with SiH4.
AB - In this report, the dynamics of the F+SiH4 reaction has been studied using the
universal crossed molecular beam method. Angular resolved time-of-flight spectra
have been measured for all reaction products in a single set of experiments. Two
different reaction channels have been observed: HF+SiH3 and SiH3F+H. Product
angular distributions as well as energy distributions were determined for these
two product channels. Experimental results show that the HF product is forward
scattered relative to the F atom beam direction, while the SiH3F product is
backward scattered relative the F atom beam direction, suggesting that two
reaction channels proceed with distinctive reaction dynamics. The relative
branching ratios of the two channels have also been estimated.
PMID- 17029430
TI - Mechanism and control of the F+H2 reaction at low and ultralow collision
energies.
AB - This article uses theoretical methods to study the dependence on stereodynamical
factors of the mechanism and reactivity of the F+H2 reaction at low and ultralow
collision energies. The impact of polarization of the H2 reactant on total and
state-to-state integral and differential cross sections is analyzed. This leads
to detailed pictures of the reaction mechanism in the cold and ultracold regimes,
accounting, in particular, for distinctions associated with the various product
states and scattering angles. The extent to which selection of reactant
polarization allows for external control of the reactivity and reaction mechanism
is assessed. This reveals that even the simplest of reactant polarization schemes
allows for fine, product state-selective control of differential and (for
reactions involving more than a single, zero orbital angular momentum partial
wave) integral cross sections.
PMID- 17029431
TI - Energy transfer between azulene and krypton: comparison between experiment and
computation.
AB - Trajectory calculations of collisional energy transfer between excited azulene
and Kr are reported, and the results are compared with recent crossed molecular
beam experiments by Liu et al. [J. Chem. Phys. 123, 131102 (2005); 124, 054302
(2006)]. Average energy transfer quantities are reported and compared with
results obtained before for azulene-Ar collisions. A collisional energy transfer
probability density function P(E,E'), calculated at identical initial conditions
as experiments, shows a peak at the up-collision branch of P(E,E') at low initial
relative translational energy. This peak is absent at higher relative
translational energies. There is a supercollision tail at the down-collision side
of the probability distribution. Various intermolecular potentials are used and
compared. There is broad agreement between experiment and computation, but there
are some differences as well.
PMID- 17029432
TI - A crossed-beam study of the F+HD-->HF+D reaction: the resonance-mediated channel.
AB - This is the last report of our extensive studies on the title reaction. Presented
here are the state-to-state differential cross section determinations at 11
collision energies, ranging from 1.30 to 4.53 kcal/mol. Together with previously
reported results at six lower energies (0.4-1.18 kcal/mol), this perhaps
represents one of the most comprehensive set of data from a single investigation
for any chemical reaction. The information contents of this set of data are
examined in detail, from which the dynamical consequences of reactive resonances
are elucidated. Qualitative interpretations of some of the major findings are
proposed. Observations that need further theoretical investigations for better
physical understanding are pointed out.
PMID- 17029433
TI - Rotationally resolved reactive scattering: imaging detailed Cl+C2H6 reaction
dynamics.
AB - The hydrogen atom abstraction reaction of Cl (2P3/2) with ethane has been studied
using the crossed molecular beam technique with dc slice imaging at collision
energies from 3.2 to 10.4 kcal/mol. The products HCl (v,J) (v = 0, J = 0-5) were
state-selectively detected using 2+1 resonance enhanced multiphoton ionization.
The images were used to obtain the center-of-mass frame product angular
distributions and translational energy release distributions. Two general
features were found in all probed HCl quantum states at 6.7 kcal/mol collision
energy, and these features have distinct translational energy release and angular
distributions, as described for HCl (v = 0, J = 2) in a recent preliminary report
[Li et al., J. Chem. Phys. 124, 011102 (2006)]. The results for HCl (v = 0, J =
2) at four collision energies were also compared to investigate the energy
dependent dynamics. We discuss the reaction in terms of a variety of models of
polyatomic reaction dynamics. The dynamics of this well studied system are more
complicated than can be accounted for by a single mechanism, and the results call
for further theoretical and experimental investigations.
PMID- 17029434
TI - Nonadiabatic effects in the H+D2 reaction.
AB - The state-to-state dynamics of the H+D2 reaction is studied by the reactant
product decoupling method using the double many-body expansion potential energy
surface. Two approaches are compared: one uses only the lowest adiabatic sheet
while the other employs both coupled diabatic sheets. Rotational distributions
for the reaction H+D2 (upsilon = 0, j = 0)-->HD(upsilon' = 3, j')+D are obtained
at eight different collision energies between 1.49 and 1.85 eV; no significant
difference are found between the two approaches. Initial state-selected total
reaction probabilities and integral cross sections are also given for energies
ranging from 0.25 up to 2.0 eV with extremely small differences being observed
between the two sets of results, thus showing that the nonadiabatic effects in
the title reaction are negligible at least for small energies below 2.0 eV.
PMID- 17029435
TI - Exact quantum calculations of the kinetic isotope effect: cross sections and rate
constants for the F+HD reaction and role of tunneling.
AB - In this paper we present integral cross sections (in the 5-220 meV collision
energy range) and rate constants (in the 100-300 K range of temperature) for the
F+HD reaction leading to HF+D and DF+H. The exact quantum reactive scattering
calculations were carried out using the hyperquantization algorithm on an
improved potential energy surface which incorporates the effects of open shell
and fine structure of the fluorine atom in the entrance channel. The results
reproduce satisfactorily molecular beam scattering experiments as well as
chemical kinetics data for both the HF and DF channels. In particular, the
agreement of the rate coefficients and the vibrational branching ratios with
experimental measurements is improved with respect to previous studies. At
thermal and subthermal energies, the rates are greatly influenced by tunneling
through the reaction barrier. Therefore exchange of deuterium is shown to be
penalized with respect to exchange of hydrogen, and the isotopic branching
exhibits a strong dependence on translational energy. Also, it is found that
rotational excitation of the reactant HD molecule enhances the production of HF
and decreases the reactivity at the D end, obtaining insight on the reaction
stereodynamics.
PMID- 17029436
TI - Inelastic scattering from glyoxal: collision kinematics rather than the
interaction potential dominates rotational channel selection.
AB - Relative cross sections have been obtained for the rotationally and
rovibrationally inelastic scattering of S1 trans-glyoxal (CHO-CHO) in its zero
point level with K' = 0 from the target gases H2, D2, and He. Emphasis is placed
on using crossed molecular beam conditions that provide several choices of
collision kinematics (center-of-mass collision energy, relative velocity, center
of-mass collision momentum) for each collision pair. The cross sections define
the state-to-state competition among numerous rotational channels involving
destination states with DeltaK' ranging from 1 to >15 for collisions with each
target gas and under every kinematic condition. They also resolve a similar
rotational competition among rovibrational channels where the torsion nu7' is
collisionally excited. The cross section sets also allow the relative overall
magnitudes of the two types of scattering to be compared. The primary motivation
of these experiments concerns the rotationally inelastic scattering. Earlier
studies with rare gases and fixed kinematics demonstrated that the distribution
of rotational cross sections is remarkably similar from one collision pair to
another. The new data show that the competition among rotational channels
actually has a small but distinct dependence on kinematic conditions. Data
analysis shows that the dependence is a systematic function of the available
collision momentum and entirely unrelated to the identity of the target gases,
including the heavier rare gases used in earlier studies. The competition among
the rotational energy transfer channels and its kinematic heritage is discussed
in the context of a classical hard ellipse model of linear momentum to angular
momentum conversion much used with room temperature systems. When adapted to our
beam conditions, the resulting account of the rotational scattering is accurate
and provides insight into the collisional details.
PMID- 17029437
TI - Intermolecular interactions of H2S with rare gases from molecular beam scattering
in the glory regime and from ab initio calculations.
AB - Integral cross sections for collisions of rotationally hot H2S molecules with
rare gas atoms (Ne, Ar, and Kr) have been measured, in the collision energy range
of 10-60 kJ mol(-1), using a molecular beam apparatus operating under high
resolution both in angle and in velocity. A well resolved glory pattern has been
measured which permitted the accurate characterization of the intermolecular
potentials both at long range (in the attractive region) and at intermediate
distances (in the well region). Considering the conditions used in the
experiments, the obtained potentials must be considered very close to the
spherical averages of the full intermolecular potential energy surfaces.
Extensive ab initio calculations have also been carried out in parallel in order
to characterize energy minima in the potential energy surfaces and energy
barriers associated to the motion of the rare gas atoms around H2S. An assessment
of the relative role of the various interaction components has been also
attempted: the combined analysis of experimental and theoretical results suggests
that H2S-rare gas aggregates are mainly bound by nearly isotropic noncovalent
interactions of the van der Waals type.
PMID- 17029438
TI - Parity-dependent rotational rainbows in D2-NO and He-NO differential collision
cross sections.
AB - The (j', Omega', epsilon') dependent differential collision cross sections of D2
with fully state selected (j = 12, Omega = 12, epsilon = -1) NO have been
determined at a collision energy of about 550 cm(-1). The collisionally excited
NO molecules are detected by (1+1') resonance enhanced multiphoton ionization
combined using velocity-mapped ion-imaging. The results are compared to He-NO
scattering results and tend to be more forward scattered for the same final
rotational state. Both for collisions of the atomic He and the molecular D2 with
NO, scattering into pairs of rotational states with the same value of n = j' -
epsilon epsilon'2 yields the same angular dependence of the cross section. This
"parity propensity rule" remains present both for spin-orbit conserving and spin
orbit changing transitions. The maxima in the differential cross sections-that
reflect rotational rainbows-have been extracted from the D2-NO and the He-NO
differential cross sections. These maxima are found to be distinct for odd and
even parity pair number n. Rainbow positions of parity changing transitions (n is
odd) occur at larger scattering angles than those of parity conserving
transitions (n is even). Parity conserving transitions exhibit-from a classical
point of view-a larger effective eccentricity of the shell. No rainbow doubling
due to collisions onto either the N-end or the O-end was observed. From a
classical point of view the presence of a double rainbow is expected. Rotational
excitation of the D2 molecules has not been observed.
PMID- 17029439
TI - Ab initio/Rice-Ramsperger-Kassel-Marcus study of the singlet C4H4 potential
energy surface and of the reactions of C2(X1 Sigmag+) with C4H4(X1A1g) and C(1D)
with C3H4 (allene and methylacetylene).
AB - Ab initio modified Gaussian-2 G2M(RCC,MP2) calculations have been performed for
various isomers and transition states on the singlet C4H4 potential energy
surface. The computed relative energies and molecular parameters have then been
used to calculate energy-dependent rate constants for different isomerization and
dissociation processes in the C4H4 system employing Rice-Ramsperger-Kassel-Marcus
theory and to predict branching ratios of possible products of the
C2(1Sigmag+)+C2H4, C(1D)+H2CCCH2, and C(1D)+H3CCCH reactions under single
collision conditions. The results show that C2 adds to the double C=C bond of
ethylene without a barrier to form carbenecyclopropane, which then isomerizes to
butatriene by a formal C2 "insertion" into the C-C bond of the C2H4 fragment.
Butatriene can rearrange to the other isomers of C4H4, including allenylcarbene,
methylenecyclopropene, vinylacetylene, methylpropargylene, cyclobutadiene,
tetrahedrane, methylcyclopropenylidene, and bicyclobutene. The major
decomposition products of the chemically activated C4H4 molecule formed in the
C2(1Sigmag+)+C2H4 reaction are calculated to be acetylene+vinylidene (48.6% at
Ecol = 0) and 1-buten-3-yne-2-yl radical [i-C4H3(X2A'), H2C=C=C=CH*]+H (41.3%).
As the collision energy increases from 0 to 10 kcal/mol, the relative yield of i
C4H3+H grows to 52.6% and that of C2H2+CCH2 decreases to 35.5%. For the
C(1D)+allene reaction, the most important products are also i-C4H3+H (55.2%) and
C2H2+CCH2 (30.1%), but for C(1D)+methylacetylene, which accesses a different
region of the C4H4 singlet potential energy surface, the calculated product
branching ratios differ significantly: 65%-69% for i-C4H3+H, 18%-14% for
C2H2+CCH2, and approximately 8% for diacetylene+H2.
PMID- 17029440
TI - Activation of methane by gold cations: guided ion beam and theoretical studies.
AB - The potential energy surface for activation of methane by the third-row
transition metal cation, Au+, is studied experimentally by examining the kinetic
energy dependence of this reaction using guided ion beam tandem mass
spectrometry. A flow tube ion source produces Au+ primarily in its 1S0 (5d10)
electronic ground state level but with some 3D (and perhaps higher lying) excited
states that can be completely removed by a suitable quenching gas (N2O). Au+
(1S0) reacts with methane by endothermic dehydrogenation to form AuCH2+ as well
as C-H bond cleavage to yield AuH+ and AuCH3+. The kinetic energy dependences of
the cross sections for these endothermic reactions are analyzed to give 0 K bond
dissociation energies (in eV) of D0(Au+ - CH2) = 3.70 +/- 0.07 and D0(Au+ -CH3) =
2.17 +/- 0.24. Ab initio calculations at the B3LYPHW + /6-311++G(3df,3p) level
performed here show good agreement with the experimental bond energies and
previous theoretical values available. Theory also provides the electronic
structures of the product species as well as intermediates and transition states
along the reactive potential energy surface. Surprisingly, the dehydrogenation
reaction does not appear to involve an oxidative addition mechanism. We also
compare this third-row transition metal system with the first-row and second-row
congeners, Cu+ and Ag+. Differences in thermochemistry can be explained by the
lanthanide contraction and relativistic effects that alter the relative size of
the valence s and d orbitals.
PMID- 17029441
TI - The effects of collision energy, vibrational mode, and vibrational angular
momentum on energy transfer and dissociation in NO2+-rare gas collisions: an
experimental and trajectory study.
AB - A combined experimental and trajectory study of vibrationally state-selected NO2+
collisions with Ne, Ar, Kr, and Xe is presented. Ne, Ar, and Kr are similar in
that only dissociation to the excited singlet oxygen channel is observed;
however, the appearance energies vary by approximately 4 eV between the three
rare gases, and the variation is nonmonotonic in rare gas mass. Xe behaves quite
differently, allowing efficient access to the ground triplet state dissociation
channel. For all four rare gases there are strong effects of NO2+ vibrational
excitation that extend over the entire collision energy range, implying that
vibration influences the efficiency of collision to internal energy conversion.
Bending excitation is more efficient than stretching; however, bending angular
momentum partially counters the enhancement. Direct dynamics trajectories for
NO2+ + Kr reproduce both the collision energy and vibrational state effects
observed experimentally and reveal that intracomplex charge transfer is critical
for the efficient energy transfer needed to drive dissociation. The strong
vibrational effects can be rationalized in terms of bending, and to a lesser
extent, stretching distortion enhancing transition to the Kr+ -NO2 charge state.
PMID- 17029442
TI - Direct observation and reactions of Cl3 radical.
AB - The broad absorption of Cl3 radical was observed between 1150 and 1350 nm using
cavity ring-down spectroscopy at 213-265 K and 50-200 Torr with He, N2, Ar, or
SF6 diluents. The absorption intensity of Cl3 increased at lower temperature and
higher pressure. SF6 was the most efficient diluent gas. The temperature
dependent equilibrium constants for Cl3 formation from Cl+Cl2 were theoretically
calculated at the MP4SDQ6-311+G(d) level. Observed decay time profiles of Cl3 and
the pressure dependence of Cl3 formation are explained by the equilibrium
reaction and a decay reaction of Cl+Cl3.
PMID- 17029443
TI - Reaction dynamics of OH+(3Sigma-)+C2H2 studied with crossed beams and density
functional theory calculations.
AB - The reactions between OH+(3Sigma-) and C2H2 have been studied using crossed ion
and molecular beams and density functional theory calculations. Both charge
transfer and proton transfer channels are observed. Products formed by carbon
carbon bond cleavage analogous to those formed in the isoelectronic O(3P)+C2H2
reaction, e.g., 3CH2 + HCO+, are not observed. The center of mass flux
distributions of both product ions at three different energies are highly
asymmetric, with maxima close to the velocity and direction of the precursor
acetylene beam, characteristic of direct reactions. The internal energy
distributions of the charge transfer products are independent of collision energy
and are peaked at the reaction exothermicity, inconsistent with either the
existence of favorable Franck-Condon factors or energy resonance. In proton
transfer, almost the entire reaction exothermicity is transformed into product
internal excitation, consistent with mixed energy release in which the proton is
transferred with both the breaking and forming bonds extended. Most of the
incremental translational energy in the two higher-energy experiments appears in
product translational energy, providing an example of induced repulsive energy
release.
PMID- 17029444
TI - Dynamics of ionization of H2 by Ne*(3P) investigated by electron spectroscopy.
AB - The Penning ionization reaction Ne*(2p(5)3s 3P)+H2-->[NeH2]+ +e- has been studied
in crossed supersonic molecular beams with electron-energy analysis at four
collision energies E = 1.83, 2.50, 3.16, and 3.89 kcal/mol. The electron kinetic
energy spectra, which directly reflect the ionizing transition region, show
resolved peaks assignable to v' = 0-4 of H2+. The vibrational populations deviate
systematically from Franck-Condon behavior, suggesting that the discrete
continuum coupling increases with H2 bond stretching. Each peak displays both
increasing breadth and increasing blueshift with increasing E, and the blueshift
also increases with increasing v'. The first two properties are consistent with a
predominantly repulsive excited-state potential-energy surface, while the last is
speculated to be a reflection of the rHH dependence of the ionic surface. Quantum
scattering calculations based on ab initio potential surfaces for the excited and
ionic states in spherical and infinite-order-sudden rigid rotor approximations
are in semiquantitative agreement with the measurements. Discrepancies suggest
changes in the imaginary, absorptive part of the excited surface, which probably
can be best effected by multiproperty fitting calculations.
PMID- 17029445
TI - Direct ab initio molecular dynamics study on a microsolvated SN2 reaction of OH
(H2O) with CH3Cl.
AB - Reaction dynamics for a microsolvated SN2 reaction OH-(H2O)+CH3Cl have been
investigated by means of the direct ab initio molecular dynamics method. The
relative center-of-mass collision energies were chosen as 10, 15, and 25
kcal/mol. Three reaction channels were found as products. These are (1) a channel
leading to complete dissociation (the products are CH3OH+Cl- +H2O: denoted by
channel I), (2) a solvation channel (the products are Cl-(H2O)+CH3OH: channel
II), and (3) a complex formation channel (the products are CH3OH...H2O+Cl-:
channel III). The branching ratios for the three channels were drastically
changed as a function of center-of-mass collision energy. The ratio of complete
dissociation channel (channel I) increased with increasing collision energy,
whereas that of channel III decreased. The solvation channel (channel II) was
minor at all collision energies. The selectivity of the reaction channels and the
mechanism are discussed on the basis of the theoretical results.
PMID- 17029446
TI - Quasiclassical trajectory study of the reaction H+CH4(nu3 = 0,1)-->CH3+H2 using a
new ab initio potential energy surface.
AB - Detailed quasiclassical trajectory calculations of the reaction H+CH4(nu3 = 0,1)-
>CH3 + H2 using a slightly updated version of a recent ab initio-based CH5
potential energy surface [X. Zhang et al., J. Chem. Phys. 124, 021104 (2006)] are
reported. The reaction cross sections are calculated at initial relative
translational energies of 1.52, 1.85, and 2.20 eV in order to make direct
comparison with experiment. The relative reaction cross section enhancement ratio
due to the excitation of the C-H antisymmetric stretch varies from 2.2 to 3.0
over this energy range, in good agreement with the experimental result of 3.0 +/-
1.5 [J. P. Camden et al., J. Chem. Phys. 123, 134301 (2005)]. The laboratory
frame speed and center-of-mass angular distributions of CH3 are calculated as are
the vibrational and rotational distributions of H2 and CH3. We confirm that this
reaction occurs with a combination of stripping and rebound mechanisms by
presenting the impact parameter dependence of these distributions and also by
direct examination of trajectories.
PMID- 17029447
TI - Crossed molecular beam studies on the reaction dynamics of O(1D)+N2O.
AB - The reaction of oxygen atom in its first singlet excited state with nitrous oxide
was investigated under the crossed molecular beam condition. This reaction has
two major product channels, NO+NO and N2+O2. The product translational energy
distributions and angular distributions of both channels were determined. Using
oxygen-18 isotope labeled O(1D) reactant, the newly formed NO can be
distinguished from the remaining NO that was contained in the reactant N2O. Both
channels have asymmetric and forward-biased angular distributions, suggesting
that there is no long-lived collision complex with lifetime longer than its
rotational period. The translational energy release of the N2+O2 channel (fT =
0.57) is much higher than that of the NO+NO channel (fT = 0.31). The product
energy partitioning into translational, rotational, and vibrational degrees of
freedom is discussed to learn more about the reaction mechanism. The branching
ratio between the two product channels was estimated. The 46N2O product of the
isotope exchange channel, 18O+44N2O-->16O+46N2O, was below the detection limit
and therefore, the upper limit of its yield was estimated to be 0.8%.
PMID- 17029448
TI - The bending vibrational levels of the acetylene cation: a case study of the
Renner-Teller effect in a molecule with two degenerate bending vibrations.
AB - Forty three vibronic levels of C2H2+, X 2Pi u, with upsilon4 = 0-6, upsilon5 = 0
3, and K = 0-4, lying at energies of 0-3520 cm(-1) above the zero-point level,
have been recorded at rotational resolution. These levels were observed by double
resonance, using 1+1' two-color pulsed-field ionization zero-kinetic-energy
photoelectron spectroscopy. The intermediate states were single rovibrational
levels chosen from the A1Au, 4nu3 (K = 1-2), 5nu3 (K = 1), nu2+4nu3 (K = 0), and
47,206 cm(-1) (K = 1) levels of C2H2. Seven of the trans-bending levels of C2H2+
(upsilon4 = 0-3, K = 0-2) had been reported previously by Pratt et al. [J. Chem.
Phys. 99, 6233 (1993)]; our results for these levels agree well with theirs. A
full analysis has been carried out, including the Renner-Teller effect and the
vibrational anharmonicity for both the trans- and cis-bending vibrations. The
rotational structure of the lowest 16 vibronic levels (consisting of the complete
set of levels with upsilon4 + upsilon5 < or = 2, except for the unobserved upper
(2Pi u component of the 2nu4 overtone) could be fitted by least squares using 16
parameters to give an rms deviation of 0.21 cm(-1). The vibronic coupling
parameter epsilon5 (about whose magnitude there has been controversy) was
determined to be -0.0273(7). For the higher vibronic levels, an additional
parameter, r45, was needed to allow for the Darling-Dennison resonance between
the two bending manifolds. Almost all the observed levels of the upsilon4 +
upsilon5 = 3 and 4 polyads (about half of the predicted number) could then be
assigned. In a final fit to 39 vibronic levels with upsilon4 + upsilon5 < or = 5,
an rms deviation of 0.34 cm(-1) was obtained using 20 parameters. An interesting
finding is that Hund's spin-coupling cases (a) and (b) both occur in the Sigmau
components of the nu4 + 2nu5 combination level. The ionization potential of C2H2
(from the lowest rotational level of the ground state to the lowest rotational
level of the cation) is found to be 91,953.77 +/- 0.09 cm(-1) (3sigma).
PMID- 17029449
TI - Probing the electronic structure of UO+ with high-resolution photoelectron
spectroscopy.
AB - The pulsed field ionization-zero kinetic energy photoelectron technique has been
used to observe the low-lying energy levels of UO+. Rotationally resolved spectra
were recorded for the ground state and the first nine electronically excited
states. Extensive vibrational progressions were characterized. Omega+ assignments
were unambiguously determined from the first rotational lines identified in each
vibronic band. Term energies, vibrational frequencies, and anharmonicity
constants for low-lying energy levels of UO+ are reported. In addition, accurate
values for the ionization energies for UO [48,643.8(2) cm(-1)] and U [49,957.6(2)
cm(-1)] were determined. The pattern of low-lying electronic states for UO+
indicates that they originate from the U3+(5f3)O2- configuration, where the
uranium ion-centered interactions between the 5f electrons are significantly
stronger than interactions with the intramolecular electric field. The latter
lifts the degeneracy of U3+ ion-core states, but the atomic angular momentum
quantum numbers remain reasonably well defined.
PMID- 17029450
TI - An empirical approach to the bond additivity model in quantitative interpretation
of sum frequency generation vibrational spectra.
AB - Knowledge of the ratios between different polarizability betai'j'k' tensor
elements of a chemical group in a molecule is crucial for quantitative
interpretation and polarization analysis of its sum frequency generation
vibrational spectroscopy (SFG-VS) spectrum at interface. The bond additivity
model (BAM) or the hyperpolarizability derivative model along with experimentally
obtained Raman depolarization ratios has been widely used to obtain such tensor
ratios for the CH3, CH2, and CH groups. Successfully, such treatment can
quantitatively reproduce the intensity polarization dependence in SFG-VS spectra
for the symmetric (SS) and asymmetric (AS) stretching modes of CH3 and CH2
groups, respectively. However, the relative intensities between the SS and AS
modes usually do not agree with each other within this model even for some of the
simplest molecular systems, such as the air/methanol interface. This fact
certainly has cast uncertainties on the effectiveness and conclusions based on
the BAM. One of such examples is that the AS mode of CH3 group has never been
observed in SFG-VS spectra from the air/methanol interface, while this AS mode is
usually very strong for SFG-VS spectra from the air/ethanol interface, other
short chain alcohol, as well as long chain surfactants. In order to answer these
questions, an empirical approach from known Raman and IR spectra is used to make
corrections to the BAM. With the corrected ratios between the betai'j'k' tensor
elements of the SS and AS modes, all features in the SFG-VS spectra of the
air/methanol and air/ethanol interfaces can be quantitatively interpreted. This
empirical approach not only provides new understandings of the effectiveness and
limitations of the bond additivity model but also provides a practical way for
its application in SFG-VS studies of molecular interfaces.
PMID- 17029451
TI - Gold as hydrogen: structural and electronic properties and chemical bonding in
Si3Au3(+0-) and comparisons to Si3H3(+0-).
AB - A single Au atom has been shown to behave like H in its bonding to Si in several
mono- and disilicon gold clusters. In the current work, we investigate the AuH
analogy in trisilicon gold clusters, Si3Au3(+0-). Photoelectron spectroscopy and
density functional calculations are combined to examine the geometric and
electronic structure of Si3Au3-. We find that there are three isomers competing
for the ground state of Si3Au3- as is the case for Si3H3-. Extensive structural
searches show that the potential energy surfaces of the trisilicon gold clusters
(Si3Au3-, Si3Au3, and Si3Au3+) are similar to those of the corresponding silicon
hydrides. The lowest energy isomers for Si3Au3- and Si3Au3 are structurally
similar to a Si3Au four-membered ring serving as a common structural motif. For
Si3Au3+, the 2pi aromatic cyclotrisilenylium auride ion, analogous to the
aromatic cyclotrisilenylium ion (Si3H3+), is the most stable species. Comparison
of the structures and chemical bonding between Si3Au3(+0-) and the corresponding
silicon hydrides further extends the isolobal analogy between Au and H.
PMID- 17029452
TI - Decay dynamics of the long-range H1Sigmag+ state of D2 and H2: experiment and
theory.
AB - We present accurate experimental measurements of the lifetimes of rovibrational
levels of the long-range H1Sigmag+ state for both D2 and H2, obtained directly
from the observation of the time-dependent decay of the fluorescence from these
excited levels. These results improve upon and extend those of Reinhold et al.
[J. Chem. Phys. 112, 10754 (2000)]. Several decay pathways are open to these
levels including fluorescence, predissociation, and autoionization. We present
theoretical results for each of these processes, each calculated using the
simplest but still appropriate level of theory. In particular, the theoretical
calculations provide a quantitative explanation of the dramatic vibrational
dependence of the observed lifetimes, the isotope dependence of the lifetimes for
levels well localized within the H potential well and therefore not subject to
significant tunneling, and an insight into the role of enhanced tunneling in
autoionization. In these calculations each of the rovibrational levels of the H
state is treated individually, without having to engage in a global coupled-state
calculation.
PMID- 17029453
TI - The calculated infrared spectrum of Cl-H2O using a new full dimensional ab initio
potential surface and dipole moment surface.
AB - We report a full dimensional, ab initio-based global potential energy surface
(PES) and dipole moment surface for Cl-H2O. Both surfaces are symmetric with
respect to interchange of the H atoms. The PES is a fit to thousands of
electronic energies calculated using the coupled-cluster method [CCSD(T)] with a
moderately large basis (aug-cc-pVTZ). Vibrational energies and wave functions are
accurately obtained using MULTIMODE. The wave function and dipole moment surface
are used to calculate and analyze the pure infrared spectrum at 0 K which is
compared with experiment. Vibrational energies and the infrared spectra for DOD
and HOD/DOH are also presented.
PMID- 17029454
TI - Vibrationally mediated photodissociation of ethene isotopic variants preexcited
to the fourth C-H stretch overtone.
AB - H and D photofragments produced via vibrationally mediated photodissociation of
jet-cooled normal ethene (C2H4), 1,2-trans-d2-ethene (HDCCDH), and 1,1-d2-ethene
(CH2CD2), initially excited to the fourth C-H stretch overtone region, were
studied for the first time. H and D vibrational action spectra and Doppler
profiles were measured. The action spectra include partially resolved features
due to rotational cooling, while the monitored room temperature photoacoustic
spectra exhibit only a very broad feature in each species. Simulation of the
spectral contours allowed determination of the band types and origins, limited
precision rotational constants, and linewidths, providing time scales for energy
redistribution. The H and D Doppler profiles correspond to low average
translational energies and show slight preferential C-H over C-D bond cleavage in
the deuterated variants. The propensities toward H photofragments emerge even
though the energy flow out of the initially prepared C-H stretch is on a
picosecond time scale and the photodissociation occurs following internal
conversion, indicating a more effective release of the light H atoms.
PMID- 17029455
TI - Collision-free photochemistry of methylazide: observation of unimolecular
decomposition of singlet methylnitrene.
AB - Methylazide photolysis at 248 nm has been investigated by ionizing photofragments
with synchrotron radiation in a photofragmentation translational spectroscopy
study. CH3N and N2 were the only observed primary products. The translational
energy release suggests a simple bond rupture mechanism forming singlet
methylnitrene, 1CH3N, and N2. Thus, these experiments reveal the unimolecular
decomposition of this highly unstable species. We explain our observations
through a mechanism which is initiated by the isomerization of 1CH3N to a highly
internally excited methanimine H2C=NH isomer, which decomposes by 1,1-H2
elimination forming HNC+H2 as well as sequential H-atom loss (N-H followed by C-H
bond cleavage), to form HCN. No evidence for dynamics on the triplet manifold of
surfaces is found.
PMID- 17029456
TI - Ultraviolet photodissociation of the van der Waals dimer (CH3I)2 revisited. II.
Pathways giving rise to neutral molecular iodine.
AB - The formation of neutral I2 by the photodissociation of the methyl iodide dimer,
(CH3I)2, excited within the A band at 249.5 nm is evaluated using velocity map
imaging. In previous work [J. Chem. Phys. 122, 204301 (2005)], we showed that the
formation of I2+ from photodissociation of the methyl iodide dimer takes place
via ionic channels (through the formation of (CH3I)2+). It is thus not possible
to detect neutral I2 by monitoring I2+. Neutral I2 is detected in this study by
monitoring I atoms arising from the photodissociation of I2. Iodine atoms from I2
photodissociation have a characteristic kinetic energy and angular anisotropy,
which is registered using velocity map imaging. We use a two-color probe scheme
involving the photodissociation of nascent I2 at 499 nm, which gives rise to I
atoms that are ionized by (2+1) resonance enhanced multiphoton ionization at
304.67 nm. Our estimate of the yield of nascent I2 is based on the comparison
with the signal from I2 at a known concentration. Using molecular beams with a
small fraction of CH3I (1% in the expanded mixture) where smaller clusters should
prevail, the production of I2 was found to be negligible. An upper estimate for
the quantum yield of I2 from (CH3I)2 dimers was found to be less than 0.4%.
Experiments with a higher fraction of CH3I (4% in the expanded mixture), which
favor the formation of larger clusters, revealed an observable formation of I2,
with an estimated translational temperature of about 820 K. We suggest that this
observed I2 signal arises from the photodissociation of several CH3I molecules in
the larger cluster by the same UV pulse, followed by recombination of two nascent
iodine atoms is responsible for neutral I2 production.
PMID- 17029457
TI - Rovibrationally selected and resolved state-to-state photoionization of ethylene
using the infrared-vacuum ultraviolet pulsed field ionization-photoelectron
method.
AB - By preparing ethylene [C2H4(X1Ag)] in selected rotational levels of the
nu11(b1u), nu2+nu12(b1u), or nu9(b2u) vibrational state with infrared (IR) laser
photoexcitation prior to vacuum ultraviolet (VUV) laser photoionization, we have
recorded rotationally resolved pulsed field ionization-photoelectron (PFI-PE)
spectra for C2H4+(X2B3u) in the energy region of 0-3000 cm(-1) above the
ionization energy (IE) of C2H4(X1Ag). Here, nu2(ag), nu9(b2u), nu11(b1u), and
nu12(b1u) represent the C-C stretching, CH2 stretching, CH2 stretching, and CH2
bending modes of C2H4(X1Ag), respectively. The fully rovibrationally resolved
spectra have allowed unambiguous symmetry assignments of the observed vibrational
bands, which in turn have provided valuable information on the photoionization
dynamics of C2H4. The IR-VUV photoionization of C2H4(X1Ag) via the nu11(b1u) or
nu2+nu12(b1u) vibrational states is found to predominantly produce vibrational
states of C2H4+(X2B3u) with b1u symmetry, which cannot be observed in single
photon VUV-PFI-PE measurements of C2H4(X1Ag). The analysis of the observed IR-VUV
PFI-PE bands has provided the IE(C2H4) = 84,790.2(2) cm(-1) and accurate
vibrational frequencies for the nu4+(au)[84.1(2) cm(-1)], nu12+(b1u)[1411.7(2)
cm(-1)], nu4+ +nu12+(b1g)[1482.5(2) cm(-1)], nu2+(ag)[1488.3(2) cm(-1)], nu2+ +
nu4+(au)[1559.2(2) cm(-1)], 2nu4+ + nu12 +(b1u)[1848.5(2) cm(-1)], 4nu4+ + nu12
+(b1u)[2558.8(2) cm(-1)], nu2+ + nu12 +(b1u)[2872.7(2) cm(-1)], and
nu11+(b1u)[2978.7(2) cm(-1)] vibrational states of C2H4+(X2B3u), where nu4+ is
the ion torsional state. The IE(C2H4) and the nu4+(au), nu2+(ag), and nu2+ + nu4+
(au) frequencies are in excellent accord with those obtained in previous single
photon VUV-PFI-PE measurements. The other ion vibrational frequencies represent
new experimental determinations. We have also performed high-level ab initio
anharmonic vibrational frequency calculations for C2H4(X1Ag) and C2H4+(X2B3u) at
the CCSD(T)/aug-cc-pVQZ level for guidance in the assignment of the IR-VUV-PFI-PE
spectra. All theoretical vibrational frequencies for the neutral and ion, except
the ion torsional frequency, are found to agree with experimental vibrational
frequencies to better than 1%.
PMID- 17029458
TI - Photodissociation and photoisomerization of alpha-fluorotoluene and 4
fluorotoluene in a molecular beam.
AB - The photodissociation of jet-cooled alpha-fluorotoluene and 4-fluorotoluene at
193 and 248 nm was studied using vacuum ultraviolet (vuv)
photoionization/multimass ion imaging techniques as well as electron impact
ionization/photofragment translational spectroscopy. Four dissociation channels
were observed for alpha-fluorotoluene at both 193 and 248 nm, including two major
channels C6H5CH2F-->C6H5CH2 (or C7H7)+F and C6H5CH2F-->C6H5CH (or C7H6)+HF and
two minor channels C6H5CH2F-->C6H5CHF+H and C6H5CH2F-->C6H5+CH2F. The vuv
wavelength dependence of the C7H7 fragment photoionization spectra indicates that
at least part of the F atom elimination channel results from the isomerization of
alpha-fluorotoluene to a seven-membered ring prior to dissociation. Dissociation
channels of 4-fluorotoluene at 193 nm include two major channels C6H4FCH3-
>C6H4FCH2+H and C6H4FCH3-->C6H4F+CH3 and two minor channels C6H4FCH3-->C6H5CH2
(or C7H7)+F and C6H4FCH3-->C6H5CH (or C7H6)+HF. The dissociation rates for alpha
fluorotoluene at 193 and 248 nm are 3.3 x 10(7) and 5.6 x 10(5) s(-1),
respectively. The dissociation rate for 4-fluorotoluene at 193 nm is 1.0 x 10(6)
s(-1). An ab initio calculation demonstrates that the barrier height for
isomerization from alpha-fluorotoluene to a seven-membered ring isomer is much
lower than that from 4-fluorotoluene to a seven-membered ring isomer. The
experimental observed differences of dissociation rates and relative branching
ratios between alpha-fluorotoluene and 4-fluorotoluene may be explained by the
differences in the six-membered ring to seven-membered ring isomerization barrier
heights, F atom elimination threshold, and HF elimination threshold between alpha
fluorotoluene and 4-fluorotoluene.
PMID- 17029459
TI - Unimolecular dissociation of the propargyl radical intermediate of the CH+C2H2
and C+C2H3 reactions.
AB - This paper examines the unimolecular dissociation of propargyl (HCCCH2) radicals
over a range of internal energies to probe the CH+HCCH and C+C2H3 bimolecular
reactions from the radical intermediate to products. The propargyl radical was
produced by 157 nm photolysis of propargyl chloride in crossed laser-molecular
beam scattering experiments. The H-loss and H2 elimination channels of the
nascent propargyl radicals were observed. Detection of stable propargyl radicals
gave an experimental determination of 71.5 (+5-10) kcal/mol as the lowest barrier
to dissociation of the radical. This barrier is significantly lower than
predictions for the lowest barrier to the radical's dissociation and also lower
than calculated overall reaction enthalpies. Products from both H2+HCCC and
H+C3H2 channels were detected at energies lower than what has been theoretically
predicted. An HCl elimination channel and a minor C-H fission channel were also
observed in the photolysis of propargyl chloride.
PMID- 17029460
TI - Spectroscopy and femtosecond dynamics of the ring opening reaction of 1,3
cyclohexadiene.
AB - The early stages of the ring opening reaction of 1,3-cyclohexadiene to form its
isomer 1,3,5-hexatriene, upon excitation to the ultrashort-lived 1 1B2 state,
were explored. A series of one-color two-photon ionization/photoelectron spectra
reveal a prominent vibrational progression with a frequency of 1350 cm(-1), which
is interpreted in a dynamical picture as resulting from the ultrafast wave packet
dynamics associated with the ring opening reaction. Photoionization in two-color
three-photon and one-color four-photon ionization schemes show an ionization
pathway via the same ultrashort-lived 1 1B2 state, and in addition, a series of
Rydberg states with quantum defects of 0.93, 0.76, and 0.15, respectively. Using
those Rydberg states as probes for the reaction dynamics in a time-resolved pump
probe experiment provides a direct observation of the elusive 2 1A1 state that
has been implicated as an intermediate step between the initially excited 1 1B2
state and the ground electronic state. The rise and decay times for the 2 1A1
state were found to be 55 and 84 fs, respectively.
PMID- 17029461
TI - The photodissociation dynamics of ozone at 193 nm: an O(1D2) angular momentum
polarization study.
AB - Polarized laser photolysis, coupled with resonantly enhanced multiphoton
ionization detection of O(1D2) and velocity-map ion imaging, has been used to
investigate the photodissociation dynamics of ozone at 193 nm. The use of
multiple pump and probe laser polarization geometries and probe transitions has
enabled a comprehensive characterization of the angular momentum polarization of
the O(1D2) photofragments, in addition to providing high-resolution information
about their speed and angular distributions. Images obtained at the probe laser
wavelength of around 205 nm indicate dissociation primarily via the Hartley band,
involving absorption to, and diabatic dissociation on, the B 1B2(3 1A1) potential
energy surface. Rather different O(1D2) speed and electronic angular momentum
spatial distributions are observed at 193 nm, suggesting that the dominant
excitation at these photon energies is to a state of different symmetry from that
giving rise to the Hartley band and also indicating the participation of at least
one other state in the dissociation process. Evidence for a contribution from
absorption into the tail of the Hartley band at 193 nm is also presented. A
particularly surprising result is the observation of nonzero, albeit small values
for all three rank K = 1 orientation moments of the angular momentum
distribution. The polarization results obtained at 193 and 205 nm, together with
those observed previously at longer wavelengths, are interpreted using an
analysis of the long range quadrupole-quadrupole interaction between the O(1D2)
and O2(1Deltag) species.
PMID- 17029462
TI - Dissociative photodetachment dynamics of the iodide-aniline cluster.
AB - The photodetachment dynamics of the iodide-aniline cluster, I-(C6H5NH2), were
investigated using photoelectron-photofragment coincidence spectroscopy at
several photon energies between 3.60 and 4.82 eV in concert with density
functional theory calculations. Direct photodetachment from the solvated I-
chromophore and a wavelength-independent autodetachment process were observed.
Autodetachment is attributed to a charge-transfer-to-solvent reaction in which
incipient continuum electrons photodetached from I- are temporarily captured by
the nascent neutral iodine-aniline cluster configured in the anion geometry.
Subsequent dissociation of the neutral cluster removes the stabilization, leading
to autodetachment of the excess electron. The dependence of the dissociative
photodetachment (DPD) and autodetachment dynamics on the final spin-orbit
electronic state of the iodine fragment is characterized. The dissociation
dynamics of the neutral fragments correlated with autodetached electrons were
found to be identical to the DPD dynamics of the I atom product spin-orbit state
closest to threshold at a given photon energy, lending support to the proposed
sequential mechanism.
PMID- 17029463
TI - Dissociation of heme from gaseous myoglobin ions studied by infrared multiphoton
dissociation spectroscopy and Fourier-transform ion cyclotron resonance mass
spectrometry.
AB - Detachment of heme prosthetic groups from gaseous myoglobin ions has been studied
by collision-induced dissociation and infrared multiphoton dissociation in
combination with Fourier-transform ion cyclotron resonance mass spectrometry.
Multiply charged holomyoglobin ions (hMbn+) were generated by electrospray
ionization and transferred to an ion cyclotron resonance cell, where the ions of
interest were isolated and fragmented by either collision with Ar atoms or
irradiation with 3 mum photons, producing apomyoglobin ions (aMbn+). Both charged
heme loss (with [Fe(III)-heme]+ and aMb(n-1)+ as the products) and neutral heme
loss (with [Fe(II)-heme] and aMbn+ as the products) were detected concurrently
for hMbn+ produced from a myoglobin solution pretreated with reducing reagents.
By reference to Ea = 0.9 eV determined by blackbody infrared radiative
dissociation for charged heme loss of ferric hMbn+, an activation energy of 1.1
eV was deduced for neutral heme loss of ferrous hMbn+ with n = 9 and 10.
PMID- 17029464
TI - Photodissociation dynamics of CBr4 at 267 nm by means of ion velocity imaging.
AB - The photodissociation dynamics of CBr4 at 267 nm has been studied using time of
flight (TOF) mass spectrometry and ion velocity imaging techniques. The
photochemical products are detected with resonance enhanced multiphoton
ionization (REMPI) as well as single-photon vacuum ultraviolet ionization at 118
nm. REMPI at 266.65 and 266.71 nm was used to detect the ground Br(2P32) and spin
orbit excited Br(2P12) atoms, respectively. The translational energy and angular
distributions are consistent with direct dissociation from an excited triplet
state and indirect dissociation from high vibrational levels on the singlet
ground state surface. Br2+ ions are also observed in the TOF spectra with a
focused 267 nm laser. The counter fragment, CBr2+, is observed when this
photolysis laser is unfocused, and photons at 118 nm are used to ionize the
radical products. The translational energy distributions of the CBr2+ and Br2+
products can be momentum matched, which indicates that molecular Br2 elimination
is one of the primary dissociation channels.
PMID- 17029465
TI - Photodissociation of nitrous oxide starting from excited bending levels.
AB - The photodissociation dynamics of N2O in the wavelength region of 203-205 nm was
studied by velocity map ion imaging. A speed resolution of 0.8% was obtained
using standard projection imaging and subpixel centroiding calculations. To
investigate N2O dissociation starting from the excited bending levels in the
ground electronic state, a supersonic molecular beam and an effusive beam were
used. The photoabsorption transition probability from the first excited bending
level in the wavelength region of 203-205 nm was estimated to be seven times
greater than that from the ground vibrational level.
PMID- 17029466
TI - Vector properties of the O(1D2) fragment produced from the photolysis of ozone in
the wavelength range of 298 to 320 nm.
AB - The speed averaged translational anisotropy and electronic angular momentum
polarization of the O(1D2) atomic fragment formed from the photodissociation of
ozone in the atmospherically important long wavelength region of the Hartley band
(298 to 320 nm) have been measured using resonance enhanced multiphoton
ionization time of flight mass spectrometry. The translational anisotropy
parameter, beta, is found to decline from 1.1 for photolysis at 300 nm to a
minimum value of 0 at 310 nm which is the threshold for production of O(1D2) in
conjunction with the O2(a 1Deltag v = 0) molecular cofragment. For photolysis
wavelengths greater than 310 nm, O(1D2) is formed from the dissociation of
internally excited ozone molecules. The corresponding beta parameters are
markedly lower than for atomic fragments produced with the same speed from the
photolysis of ground state ozone molecules. This result is consistent with two
different pathways contributing to the photolysis of internally excited ozone at
the longest wavelengths studied corresponding to initial internal excitation
either in the symmetric or asymmetric stretching vibration. In addition, the
polarization of the atomic angular momentum has been determined with the
incoherent polarization parameters a0(2)(||) and a0(2)(_|) increasing from values
of -0.53 and -0.62 at 300 nm to -0.37 and -0.19 at 317 nm, consistent with the
increasing contribution from the photolysis of internally excited ozone as the
dissociation wavelength lengthens. Evaluation of these alignment parameters
allows the populations of the magnetic substrates, mj, to be determined. For
example, for a photolysis wavelength of 303 nm the populations of mj = 0, +/- 1,
+/- 2 are in the ratio of 0.36: 0.56: 0.08 and this ratio is essentially
independent of the photolysis wavelength. The coherent contribution to the atomic
polarization is quantified by the Re{a1(2)(||, _|)} and Im{a1(1)(||, _|)}
parameters and these are found to vary from -0.21 and 0.21 at 300 nm to -0.04 and
0.24 at 313 nm, respectively.
PMID- 17029467
TI - Enhanced selectivity and yield in multichannel photodissociation reactions:
application to CH3I.
AB - We develop a method to improve the population transfer and final-channel control
of multichannel photodissociation reactions. The method is applied to the
photodissociation of methyl iodide, CH3(v)+I*(2P1/2)<--CH3I-->CH3(v)+I(2P3/2).
Our method is based on simultaneously exciting many two-photon pathways that lead
to the same final outcome, each proceeding via a different intermediate bound
state. The selectivity of the final product state(s) is a result of coherently
controlled interference between the quantum pathways. The improvement in the
population transfer yield from the ground state to the selected dissociative
channel(s) is made possible by executing the process in an adiabatic fashion.
PMID- 17029468
TI - Two-color visible/vacuum ultraviolet photoelectron imaging dynamics of Br2.
AB - An experimental two-color photoionization dynamics study of laser-excited Br2
molecules is presented, combining pulsed visible laser excitation and tunable
vacuum ultraviolet (VUV) synchrotron radiation with photoelectron imaging. The X
1Sigmag + -B 3Pi0+u transition in Br2 is excited at 527 nm corresponding
predominantly to excitation of the v' = 28 vibrational level in the B 3Pi0+u
state. Tunable VUV undulator radiation in the energy range of 8.40-10.15 eV is
subsequently used to ionize the excited molecules to the X 2Pi32,12 state of the
ion, and the ionic ground state is probed by photoelectron imaging. Similar
experiments are performed using single-photon synchrotron ionization in the
photon energy range of 10.75-12.50 eV without any laser excitation. Photoelectron
kinetic energy distributions are extracted from the photoelectron images. In the
case of two-color photoionization using resonant excitation of the intermediate B
3Pi0+u state, a broad distribution of photoelectron kinetic energies is observed,
and in some cases even a bimodal distribution, which depends on the VUV photon
energy. In contrast, for single-photon ionization, a single nearly Gaussian
shaped distribution is observed, which shifts to higher energy with photon
energy. Simulated spectra based on Franck-Condon factors for the transitions
Br2(X 1Sigmag+, v" = 0)-Br2 +(X 2Pi12,32, v+) and Br2(B 3Pi0+u, v' = 28)-Br2 +(X
2Pi12,32, v+) are generated. Comparison of these calculated spectra with the
measured images suggests that the differences in the kinetic energy distributions
for the two ionization processes reflect the different extensions of the
vibrational wave functions in the v" = 0 electronic ground state (X 1Sigmag+)
versus the electronically and vibrationally excited state (B 3Pi0+u, v' = 28).
PMID- 17029469
TI - Anisotropy of photofragment recoil as a function of dissociation lifetime,
excitation frequency, rotational level, and rotational constant.
AB - Quantum mechanical calculations of photofragment angular distributions have been
performed as a function of the frequency of excitation, the lifetime of the
dissociative state, the rotational level, and the rotational constant. In the
limit of high J values and white, incoherent excitation, the general results are
found to agree exactly with both those of Mukamel and Jortner [J. Chem. Phys. 61,
5348 (1974)] and those of Jonah [J. Chem. Phys. 55, 1915 (1971)]. Example
calculations describe how the anisotropy is dependent on the degree of
broadening, the rotational constant, the initial rotational level, and the
frequency of excitation. Applications are also made to interpret experimental
results on the photodissociation of ClO via the 11-0, 10-0, and 6-0 bands of the
A 2Pi3/2 -X 2Pi3/2 transition and on the photodissociation of O2 via the 0-0 band
of the E 3Sigmau- -X 3Sigmag- transition.
PMID- 17029470
TI - Dynamics of the 193 nm photodissociation of dichlorocarbene.
AB - The dynamics of the 193 nm photodissociation of the CCl2 molecule have been
investigated in a molecular beam experiment. The CCl2 parent molecule was
generated in a molecular beam by pyrolysis of CHCl3, and both CCl2 and the CCl
photofragment were detected by laser fluorescence excitation. The 193 nm
attenuation cross section was estimated from the reduction of the CCl2 signal as
a function of the photolysis laser fluence. The internal state distribution of
the CCl photofragment was derived from analysis of laser fluorescence excitation
spectra in the A 2Delta-X 2Pi band system. Most of the energy available to the
CCl(X 2Pi)+Cl fragments appears as translational energy. The CCl fragment
rotational energy is much less than predicted in an impulsive model. The excited
electronic state appears to dissociate indirectly, through coupling with a
repulsive state arising from the ground-state CCl(X 2Pi)+Cl asymptote. The
identity of the initially excited electronic state is discussed on the basis of
what is known about the CCl2 electronic states.
PMID- 17029471
TI - High resolution photofragment translational spectroscopy studies of the near
ultraviolet photolysis of phenol.
AB - The fragmentation dynamics of gas phase phenol molecules following excitation at
many wavelengths in the range 279.145 > or = lambdaphot > or = 206.00 nm have
been investigated by H Rydberg atom photofragment translational spectroscopy.
Many of the total kinetic energy release (TKER) spectra so derived show
structure, the analysis of which confirms the importance of O-H bond fission and
reveals that the resulting phenoxyl cofragments are formed in a very limited
subset of their available vibrational state density. Spectra recorded at
lambdaphot > or = 248 nm show a feature centered at TKER approximately 6500 cm(
1). These H atom fragments, which show no recoil anisotropy, are rationalized in
terms of initial S1<--S0 (pi*<--pi) excitation, and subsequent dissociation via
two successive radiationless transitions: internal conversion to ground (S0)
state levels carrying sufficient O-H stretch vibrational energy to allow
efficient transfer towards, and passage around, the conical intersection (CI)
between the S0 and S2(1pisigma*) potential energy surfaces (PESs) at larger R(O
H), en route to ground state phenoxyl products. The observed phenoxyl product
vibrations indicate that parent modes nu16a and nu11 can both promote
nonadiabatic coupling in the vicinity of the S0S2 CI. Spectra recorded at
lambdaphot < or = 248 nm reveal a faster, anisotropic distribution of recoiling H
atoms, centered at TKER approximately 12,000 cm(-1). These we attribute to
H+phenoxyl products formed by direct coupling between the optically excited
S1(1pi pi*) and repulsive S2(1pi sigma*) PESs. Parent mode nu16b is identified as
the dominant coupling mode at the S1/S2 CI, and the resulting phenoxyl radical
cofragments display a long progression in nu18b, the C-O in-plane wagging mode.
Analysis of all structured TKER spectra yields D0(H-OC6H5) = 30,015 +/- 40 cm(
1). The present findings serve to emphasize two points of wider relevance in
contemporary organic photochemistry: (i) The importance of 1) pi sigma* states in
the fragmentation of gas phase heteroaromatic hydride molecules, even in cases
where the 1pi sigma* state is optically dark. (ii) The probability of observing
strikingly mode-specific product formation, even in "indirect" predissociations,
if the fragmentation is driven by ultrafast nonadiabatic couplings via CIs
between excited (and ground) state PESs.
PMID- 17029472
TI - 248 nm photolysis of CH2Br2 by using cavity ring-down absorption spectroscopy:
Br2 molecular elimination at room temperature.
AB - Following photodissociation of CH2Br2 at 248 nm, Br2 molecular elimination is
detected by using a tunable laser beam, as crossed perpendicular to the
photolyzing laser beam in a ring-down cell, probing the Br2 fragment in the B
3Piou+ -X 1Sigmag+ transition. The nascent vibrational population is obtained,
yielding a population ratio of Br2(v = 1)Br2(v = 0) to be 0.7 +/- 0.2. The
quantum yield for the Br2 elimination reaction is determined to be 0.2 +/- 0.1.
Nevertheless, when CH2Br2 is prepared in a supersonic molecular beam under cold
temperature, photofragmentation gives no Br2 detectable in a time-of-flight mass
spectrometer. With the aid of ab initio potential energy calculations, a
plausible pathway is proposed. Upon excitation to the 1B1 or 3B1 state, C-Br bond
elongation may change the molecular symmetry of Cs and enhance the resultant 1
1,3A'-X 1A' (or 1 1,3B1-X 1A1 as C2v is used) coupling to facilitate the process
of internal conversion, followed by asynchronous concerted photodissociation.
Temperature dependence measurements lend support to the proposed pathway.
PMID- 17029473
TI - Explosive photodissociation of methane induced by ultrafast intense laser.
AB - A new type of molecular fragmentation induced by femtosecond intense laser at the
intensity of 2 x 10(14) W/cm2 is reported. For the parent molecule of methane,
ethylene, n-butane, and 1-butene, fluorescence from H (n = 3-->2), CH (A 2Delta,
B 2Sigma-, and C 2Sigma+-->X 2Pi), or C2 (d 3Pi g-->a 3Pi u) is observed in the
spectrum. It shows that the fragmentation is a universal property of neutral
molecule in the intense laser field. Unlike breaking only one or two chemical
bonds in conventional UV photodissociation, the fragmentation caused by the
intense laser undergoes vigorous changes, breaking most of the bonds in the
molecule, like an explosion. The fragments are neutral species and cannot be
produced through Coulomb explosion of multiply charged ion. The laser power
dependence of CH (A-->X) emission of methane on a log-log scale has a slope of 10
+/- 1. The fragmentation is thus explained as multiple channel dissociation of
the superexcited state of parent molecule, which is created by multiphoton
excitation.
PMID- 17029474
TI - The time scale for electronic reorganization upon sudden ionization of the water
and water-methanol hydrogen bonded dimers and of the weakly bound NO dimer.
AB - When the valence molecular orbital is localized sudden ionization can cause the
nascent hole to move rapidly even before any relaxation of the geometry occurs.
Hydrogen bonded clusters offer suitable test systems where the hole is initially
localized on one moiety. Computational studies are reported for the water dimer
and water-methanol bimer. The local ionization potential of water is different in
the methanol-water and water-methanol conformers and this difference is very
clearly reflected in the dynamics of charge migration. For the NO dimer the
results are that its structure is symmetric so that the two NO molecules are
equivalent and do not exhibit the required localization. The role of symmetry is
also evident in the charge propagation for holes created in different orbitals.
Localization of the initial hole distribution even if absent in the bare molecule
can still be induced by the intense electric field of a sudden photoionization.
This effect is computationally studied for the NO dimer in the presence of a
static electric field.
PMID- 17029475
TI - Applied reaction dynamics: efficient synthesis gas production via single
collision partial oxidation of methane to CO on Rh111.
AB - Supersonic molecular beams have been used to determine the yield of CO from the
partial oxidation of CH4 on a Rh111 catalytic substrate, CH4+12O2-->CO+2H2, as a
function of beam kinetic energy. These experiments were done under ultrahigh
vacuum conditions with concurrent molecular beams of O2 and CH4, ensuring that
there was only a single collision for the CH4 to react with the surface. The
fraction of CH4 converted is strongly dependent on the normal component of the
incident beam's translational energy, and approaches unity for energies greater
than approximately 1.3 eV. Comparison with a simplified model of the methane
Rh111 reactive potential gives insight into the barrier for methane dissociation.
These results demonstrate the efficient conversion of methane to synthesis gas,
CO+2H2, are of interest in hydrogen generation, and have the optimal
stoichiometry for subsequent utilization in synthetic fuel production (Fischer
Tropsch or methanol synthesis). Moreover, under the reaction conditions explored,
no CO2 was detected, i.e., the reaction proceeded with the production of very
little, if any, unwanted greenhouse gas by-products. These findings demonstrate
the efficacy of overcoming the limitations of purely thermal reaction mechanisms
by coupling nonthermal mechanistic steps, leading to efficient C-H bond
activation with subsequent thermal heterogeneous reactions.
PMID- 17029476
TI - The collimation angle shift of desorbing product N2 in a steady-state N2O+CO
reaction on Rh(110).
AB - The angular distribution of desorbing product N2 was studied in N2O
decompositions on Rh(110) in the temperature range of 60-700 K. The N2 desorption
collimates along 62 degrees -68 degrees off normal toward either the [001] or
[001] direction in a transient N2O decomposition below ca. 470 K or in the steady
state N2O+CO reaction above 540 K. In the steady-state reaction at the
temperature from ca. 470 to 540 K, however, the collimation angle shifts from 62
degrees to 45 degrees with decreasing surface temperature. This angle shift is
ascribed to the steric hindrance by coadsorbed CO because the N2 collimation in
transient N2O decomposition at around 65 degrees is recovered in the range of 380
500 K by an abrupt CO pressure drop followed by the decrease in CO coverage. N2O
is oriented along the [001] direction before dissociation. A scattering model of
the nascent N2 by adsorbed CO is proposed, yielding smaller collimation angles.
PMID- 17029477
TI - Infrared spectroscopy of large ammonia clusters as a function of size.
AB - We have measured the vibrational spectra of large ammonia (NH3)n clusters by
photofragment spectroscopy in the spectral range from 3150 to 3450 cm(-1) for the
average sizes n = 29, 80, 212, 447, and 989 and by depletion spectroscopy for
n=8. The spectra are dominated by peaks around 3385 cm(-1) which are attributed
to the asymmetric nu3 NH-stretch mode. Two further peaks between 3200 and 3260
cm(-1) have about equal intensity for n = 8 and 29, but only about 0.40 of the
intensity of the nu3 peak for the larger sizes. The spectra for the smallest and
largest size agree with those obtained by Fourier transform infrared spectroscopy
in slit jet expansion and collision cells, respectively. By accompanying
calculation we demonstrate that the energetic order of the spectral features
originating from the bending overtone 2nu4 and the symmetric NH-stretch nu1 in
the range from 3150 to 3450 cm(-1) is changed between n = 10 and 100, while the
asymmetric NH-stretch nu3 only exhibits a moderate redshift. The reason is the
coupling of the ground state modes to the overtones.
PMID- 17029478
TI - How many metal atoms are needed to dehydrogenate an ethylene molecule on metal
clusters?: Correlation between reactivity and electronic structures of Fen+,
Con+, and Nin+.
AB - The absolute cross section for dehydrogenation of an ethylene molecule on Mn+
[Fen+ (n = 2-28), Con+ (n = 8-29), and Nin+ (n = 3-30)] was measured as a
function of the cluster size n in a gas-beam geometry at a collision energy of
0.4 eV in the center-of-mass frame in an apparatus equipped with a tandem-type
mass spectrometer. It is found that (1) the dehydrogenation cross section
increases rapidly above a cluster size of approximately 18 on Fen+, approximately
13 and approximately 18 on Con+, and approximately 10 on Nin+ and (2) the rapid
increase of the cross section for Mn+ occurs at a cluster size where the 3d
electrons start to contribute to the highest occupied levels of Mn+. These
findings lead us to conclude that the 3d electrons of Mn+ play a central role in
the dehydrogenation on Mn+.
PMID- 17029479
TI - Time-resolved study of solvent-induced recombination in photodissociated IBr
(CO2)n clusters.
AB - We report the time-resolved recombination of photodissociated IBr-(CO2)n (n = 5
10) clusters following excitation to the dissociative IBr-A' 2Pi12 state of the
chromophore via a 180 fs, 795 nm laser pulse. Dissociation from the A' state of
the bare anion results in I- and Br products. Upon solvation with CO2, the IBr-
chromophore regains near-IR absorption only after recombination and vibrational
relaxation on the ground electronic state. The recombination time was determined
by using a delayed femtosecond probe laser, at the same wavelength as the pump,
and detecting ionic photoproducts of the recombined IBr- cluster ions. In sharp
contrast to previous studies involving solvated I2-, the observed recombination
times for IBr-(CO2)n increase dramatically with increasing cluster size, from 12
ps for n = 5 to 900 ps for n = 8,10. The nanosecond recombination times are
especially surprising in that the overall recombination probability for these
cluster ions is unity. Over the range of 5-10 solvent molecules, calculations
show that the solvent is very asymmetrically distributed, localized around the Br
end of the IBr- chromophore. It is proposed that this asymmetric solvation delays
the recombination of the dissociating IBr-, in part through a solvent-induced
well in the A' state that (for n = 8,10) traps the evolving complex. Extensive
electronic structure calculations and nonadiabatic molecular dynamics simulations
provide a framework to understand this unexpected behavior.
PMID- 17029480
TI - Photodissociation of polycrystalline and amorphous water ice films at 157 and 193
nm.
AB - The photodissociation dynamics of amorphous solid water (ASW) films and
polycrystalline ice (PCI) films at a substrate temperature of 100 K have been
investigated by analyzing the time-of-flight (TOF) mass spectra of photofragment
hydrogen atoms at 157 and 193 nm. For PCI films, the TOF spectrum recorded at 157
nm could be characterized by a combination of three different (fast, medium, and
slow) Maxwell-Boltzmann energy distributions, while that measured at 193 nm can
be fitted in terms of solely a fast component. For ASW films, the TOF spectra
measured at 157 and 193 nm were both dominated by the slow component, indicating
that the photofragment H atoms are accommodated to the substrate temperature by
collisions. H atom formation at 193 nm is attributed to the photodissociation of
water species on the ice surface, while at 157 nm it is ascribable to a mixture
of surface and bulk photodissociations. Atmospheric implications in the high
latitude mesopause region of the Earth are discussed.
PMID- 17029481
TI - Molecular dynamics of haloalkane corral formation and surface halogenation at
Si(111)-7 x 7.
AB - Long-chain organic molecules, 1-halododecane, RX (X = Cl,Br), adsorbed on Si(111)
7 x 7 were shown to form stable dimeric corrals; type I around corner holes and
type II around corner adatoms S. Dobrin et al. [Surf. Sci. Lett. 600, L43
(2006)]. Here we examine the molecular dynamics of corral formation, in which
mobile physisorbed adsorbates spontaneously convert to immobile. At high coverage
the mechanism gives evidence of involving collisions between mobile vertical
monomers, giving types I and II immobile horizontal dimers, vD +vD -->h2 (I, II).
At low coverage mobile vertical monomers collide with immobile horizontal ones to
form largely type-II corrals, vD + h-->h2 (II). Thermal reaction of corrals with
X = Br brominates the surface by two distinct molecular pathways, thought to have
more general applicability: "daughter-mediated" reaction of vertical v(A) with a
low activation energy (here Ea approximately 5 kcal mol(-1)) and "parent
mediated" reaction of horizontal h or h2 with high activation energy (here Ea =
29 kcal mol(-1)).
PMID- 17029482
TI - Ultrafast vectorial and scalar dynamics of ionic clusters: azobenzene solvated by
oxygen.
AB - The ultrafast dynamics of clusters of trans-azobenzene anion (A-) solvated by
oxygen molecules was investigated using femtosecond time-resolved photoelectron
spectroscopy. The time scale for stripping off all oxygen molecules from A- was
determined by monitoring in real time the transient of the A- rise, following an
800 nm excitation of A- (O2)n, where n = 1-4. A careful analysis of the time
dependent photoelectron spectra strongly suggests that for n > 1 a quasi-O4 core
is formed and that the dissociation occurs by a bond cleavage between A- and
conglomerated (O2)n rather than a stepwise evaporation of O2. With time and
energy resolutions, we were able to capture the photoelectron signatures of
transient species which instantaneously rise (<100 fs) then decay. The transient
species are assigned as charge-transfer complexes: A.O2- for A- O2 and A.O4-(O2)n
2 for A-(O2)n, where n = 2-4. Subsequent to an ultrafast electron recombination,
A- rises with two distinct time scales: a subpicosecond component reflecting a
direct bond rupture of the A- -(O2)n nuclear coordinate and a slower component
(1.6-36 ps, increasing with n) attributed to an indirect channel exhibiting a
quasistatistical behavior. The photodetachment transients exhibit a change in the
transition dipole direction as a function of time delay. Rotational dephasing
occurs on a time scale of 2-3 ps, with a change in the sign of the transient
anisotropy between A- O2 and the larger clusters. This behavior is a key
indicator of an evolving cluster structure and is successfully modeled by
calculations based on the structures and inertial motion of the parent clusters.
PMID- 17029483
TI - A mass and time-of-flight spectroscopy study of the formation of clusters in free
jet expansions of normal D2.
AB - The mass spectra in the range of 2(D+)-38(D19+) amu of clusters formed in a
supersonic free-jet expansion of normal D2 are investigated as functions of
source temperature in the range of 95-220 K and of source pressure in the range
of 10-120 bars. For some of the small ion fragments, time-of-flight distributions
are also measured. For large clusters (n > 200) the intensities of the odd
numbered ion fragments exhibit magic numbers at D9+ and D15+ in accordance with
previous experiments and calculations. The even-numbered ion fragments have much
smaller intensities and exhibit new magic numbers at D10+ and D14+. For source
conditions such that large clusters are formed, the intensities of the various
different ion fragments are observed to saturate beyond a certain source
pressure. At lower source pressures, where only small clusters are formed, the
terminal mole fractions of the neutral dimers are analyzed in the light of
available theories which take into account both the thermodynamics and the
kinetics of the expansion. At higher source pressures and lower temperatures,
where larger clusters are formed, the sizes of the neutral clusters are estimated
using scaling laws and are found to be consistent with the mass spectra and
measured time-of-flight distributions. By using a variety of techniques it has
been possible to obtain reliable conclusions about the neutral cluster sizes for
the present free-jet expansion conditions.
PMID- 17029484
TI - Manipulation of slow molecular beams by static external fields.
AB - Deflection by magnetic or electric field gradients has long been used to analyze
or to alter the translational trajectories of neutral gas-phase atoms or
molecules. Recent work has developed sources of slow, cold molecular beams that
offer means to enhance markedly the attainable deflections, which are inversely
proportional to the translational kinetic energy. The sensitivity and resolution
can thus be much increased, typically by factors of 10(2)-10(4). We illustrate
ways to exploit this enhanced deflection capability, particularly when balancing
electric and magnetic deflections. Chemical scope can be greatly extended by
utilizing feeble but ubiquitous interactions, especially the induced electric
dipole due to the molecular polarizability and magnetic moments resulting from
molecular rotation or nuclear spins. We also examine the effect of non-Maxwellian
velocity distributions produced by supersonic expansions or by quantum statistics
(pertinent for ultracold beams). Generic plots are provided, employing
dimensionless variables, to facilitate the design and interpretation of
experiments with deflections amplified by low kinetic energy.
PMID- 17029485
TI - A new time evolving Gaussian series representation of the imaginary time
propagator.
AB - Frantsuzov and Mandelshtam [J. Chem. Phys. 121, 9247 (2004)] have recently
demonstrated that a time evolving Gaussian approximation (TEGA) to the imaginary
time propagator exp(-betaH) is useful for numerical computations of
anharmonically coupled systems with many degrees of freedom. In this paper we
derive a new exact series representation for the imaginary time propagator whose
leading order term is the TEGA. One can thus use the TEGA not only as an
approximation but also to obtain the exact imaginary time propagator. We also
show how the TEGA may be generalized to provide a family of TEGA's. Finally, we
find that the equations of motion governing the evolution of the center and width
of the Gaussian may be thought of as introducing a quantum friction term to the
classical evolution equations.
PMID- 17029486
TI - Construction and calibration of an instrument for three-dimensional ion imaging.
AB - We describe a new instrument based on a delay-line detector for imaging the
complete three-dimensional velocity distribution of photoionized products from
photoinitiated reactions. Doppler-free [2+1] resonantly enhanced multiphoton
ionization (REMPI) of H and D atoms formed upon photolysis of HBr and DBr in the
range 203 nm < or = lambda photolysis < or = 243 nm yields radial speeds measured
to be accurate within 1% of those calculated. The relative speed resolution is
about 5% and limited by photoionization recoil broadening. A relative speed
resolution of 3.4% is obtained for [3+1] REMPI, which minimizes the ionization
recoil. We also determine the branching ratio between ground-state and spin-orbit
excited product channels and their associated anisotropies. We find that DBr
photolysis dynamics differs slightly from its HBr counterpart.
PMID- 17029487
TI - Local angular momentum-local impact parameter analysis: derivation and properties
of the fundamental identity, with applications to the F+H2, H+D2, and Cl+HCl
chemical reactions.
AB - The technique of local angular momentum-local impact parameter (LAM-LIP) analysis
has recently been shown to provide valuable dynamical information on the angular
scattering of chemical reactions under semiclassical conditions. The LAM-LIP
technique exploits a nearside-farside (NF) decomposition of the scattering
amplitude, which is assumed to be a Legendre partial wave series. In this paper,
we derive the "fundamental NF LAM identity," which relates the full LAM to the NF
LAMs (there is a similar identity for the LIP case). Two derivations are
presented. The first uses complex variable techniques, while the second exploits
an analogy between the motion of the scattering amplitude in the Argand plane
with changing angle and the classical mechanical motion of a particle in a plane
with changing time. Alternative forms of the fundamental LAM-LIP identity are
described, one of which gives rise to a CLAM-CLIP plot, where CLAM denotes (Cross
section) x LAM and CLIP denotes (Cross section) x LIP. Applications of the NF LAM
theory, together with CLAM plots, are reported for state-to-state transitions of
the benchmark reactions F+H2-->FH+H, H+D2-->HD+D, and Cl+HCl-->ClH+Cl, using as
input both numerical and parametrized scattering matrix elements. We use the
fundamental LAM identity to explain the important empirical observation that a NF
cross section analysis and a NF LAM analysis provide consistent (and
complementary) information on the dynamics of chemical reactions.
PMID- 17029488
TI - Numerical generation of hyperspherical harmonics for tetra-atomic systems.
AB - A numerical generation method of hyperspherical harmonics for tetra-atomic
systems, in terms of row-orthonormal hyperspherical coordinates-a hyper-radius
and eight angles-is presented. The nine-dimensional coordinate space is split
into three three-dimensional spaces, the physical rotation, kinematic rotation,
and kinematic invariant spaces. The eight-angle principal-axes-of-inertia
hyperspherical harmonics are expanded in Wigner rotation matrices for the
physical and kinematic rotation angles. The remaining two-angle harmonics defined
in kinematic invariant space are expanded in a basis of trigonometric functions,
and the diagonalization of the kinetic energy operator in this basis provides
highly accurate harmonics. This trigonometric basis is chosen to provide a
mathematically exact and finite expansion for the harmonics. Individually, each
basis function does not satisfy appropriate boundary conditions at the poles of
the kinetic energy operator; however, the numerically generated linear
combination of these functions which constitutes the harmonic does. The size of
this basis is minimized using the symmetries of the system, in particular,
internal symmetries, involving different sets of coordinates in nine-dimensional
space corresponding to the same physical configuration.
PMID- 17029489
TI - The integration of measurement and management for the treatment of bipolar
disorder: a STEP-BD model of collaborative care in psychiatry.
AB - Patients with bipolar disorder are among the most challenging to treat. These
patients frequently present with complex mood and other symptoms that change over
time, complex psychiatric and medical comorbid conditions, and multiple
medications. Clinicians rarely systematically assess or measure all of these
factors and instead rely on memory and general impressions. It is imperative that
clinicians systematically track and monitor these relevant variables to ensure
treatment decisions are based on precise clinical data. By integrating
measurement and management, clinicians and patients can collaborate to assess the
effectiveness of treatments and to make joint decisions about critical points at
which to adjust treatment. This method was shown to be successful in the National
Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for
Bipolar Disorder (STEP-BD).
PMID- 17029490
TI - Illness course, comorbidity, gender, and suicidality in patients with bipolar
disorder.
AB - Among patients with bipolar disorder, comorbid conditions are common. Comorbidity
is associated with a more difficult course of illness (such as longer episodes,
shorter time euthymic, and earlier age at onset) and an increase in related
problems (such as suicidality and violence). Data from the Systematic Treatment
Enhancement Program for Bipolar Disorder (STEP-BD) reveal that anxiety disorders,
attention-deficit/hyperactivity disorder, and substance and alcohol use disorder
are conditions that commonly co-occur with bipolar disorder. This article details
these findings and discusses the complications associated with these comorbid
conditions. STEP-BD data about gender differences are also discussed, and
correlates of suicidal ideation among patients entering the program are
described.
PMID- 17029491
TI - Implementing evidence-based treatment of manic and mixed episodes.
AB - Manic and mixed episodes can be challenging to treat despite published guidelines
and algorithms. An alternative iterative approach that offers evidence-based
treatment options at critical decision points may help to individualize care.
Implementing such an approach begins with making a diagnosis and recognizing
individual patient factors, weighing treatment options, and developing a menu of
reasonable treatment choices based on the best available evidence. A critical
review of the evidence is needed to ensure that interventions with the highest
quality evidence are offered preferentially and that relevant individual factors
are considered. Educating patients, negotiating treatment options, and selecting
a pathway of care with the patient are important steps before initiating an
intervention. After initiating an intervention, follow-up proceeds by measuring
efficacy and adverse events with the aim of determining whether or not the
patient is benefiting from treatment. Based on this knowledge, new individual
factors are known and new evidence can be reviewed, so the cycle begins again.
Using this iterative approach to treat patients with bipolar disorder in manic
and mixed episodes promotes personalized care and relies on understanding the
quality of evidence for the treatments commonly used to treat these phases of
bipolar disorder.
PMID- 17029492
TI - The evidence for antidepressant use in bipolar depression.
AB - Mood elevation, which includes mania, hypomania, and mixed states, was previously
considered the defining symptom of bipolar disorder, but bipolar depression by
comparison is actually a much more substantial challenge to diagnose and treat.
Recent studies, including research by the Systematic Treatment Enhancement
Program for Bipolar Disorder (STEP-BD), found that patients with bipolar disorder
spend longer periods of time in depressive episodes and are more likely to
relapse to depression compared with mania or hypomania. However, the treatment of
bipolar depression is hampered by the limited number and varying quality of
available studies of pharmacologic treatments to guide clinical decision making.
Clinicians should rely on studies with the highest level of evidence (category A)
when prescribing appropriate antidepressant treatments. The standard care
pathways outlined by STEP-BD to aid clinicians in treating varying phases of
bipolar disorder provide data on the use of various treatments for bipolar
depression and their outcomes. While some treatments have the potential to induce
mania, others appear to have some efficacy without inducing mania.
PMID- 17029493
TI - Treatment of rapid-cycling bipolar disorder.
AB - Rapid-cycling bipolar disorder is associated with poorer treatment response,
poorer long-term prognosis, and probable higher suicide risk than bipolar
disorder without rapid cycling. Patients with rapid cycling tend to experience
more depressive than manic episodes, and the depressive episodes tend to be more
refractory in nature compared with those in patients without rapid cycling.
Results from studies of rapid cycling show that antidepressant use is most likely
associated with the onset or worsening of rapid cycling. Controversy also exists
as to whether rapid cycling is a transitory phenomenon in the course of bipolar
illness or a more chronic condition better characterized as a subtype of the
illness. Results from the first 500 patients with bipolar I or bipolar II
disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar
Disorder (STEP-BD) study found an association between rapid cycling and
depression and younger age at illness onset. Treatment involves a 3-part pathway
to manage rapid cycling that includes reducing or stopping any possible cycle
promoting agents, adding or optimizing mood stabilizers, and using experimental
or putative treatments for persistent rapid cycling after more traditional
treatments have failed. Effective treatments for some patients with rapid-cycling
bipolar disorder currently include lithium, divalproex, lamotrigine,
carbamazepine, atypical antipsychotics, and psychosocial therapy.
PMID- 17029494
TI - A review of evidence-based psychosocial interventions for bipolar disorder.
AB - Various forms of psychosocial intervention have been found efficacious as
adjunctive treatments for bipolar disorder, including family-focused therapy,
interpersonal and social rhythm therapy, cognitive-behavioral therapy, and
individual or group psychoeducation. When used in conjunction with
pharmacotherapy, these interventions may prolong time to relapse, reduce symptom
severity, and increase medication adherence. Family-focused therapy seeks to
reduce the high levels of stress and conflict in the families of bipolar
patients, thereby improving the patient's illness course. Interpersonal and
social rhythm therapy focuses on stabilizing the daily and nightly routines of
bipolar patients and resolving key interpersonal problems. Cognitive-behavioral
therapy assists patients in modifying dysfunctional cognitions and behaviors that
may aggravate the course of bipolar disorder. Group psychoeducation provides a
supportive, interactive setting in which patients learn about their disorder and
how to cope with it. This article discusses each of these interventions and
summarizes the evidence for their efficacy in randomized trials. Recommendations
for implementing psychosocial interventions in clinical practice are also given.
PMID- 17029495
TI - Phytochrome-mediated inhibition of coleoptile growth in rice: age-dependency and
action spectra.
AB - Phytochrome has been shown to be the major photoreceptor involved in the photo
inhibition of coleoptile growth in Japonica-type rice (Oryza sativa L.). We have
characterized this typical photomorphogenetic response of rice using mutants
deficient in phytochrome A (phyA) and phytochrome B (phyB) and with respect to
age-dependency and action spectra. Seedlings were irradiated with a pulse of
light 40 h or 80 h after germination (i.e. at an early or late developmental
stage) and the final coleoptile length of these seedlings was determined. A
saturating pulse of red light (R) had a stronger effect when it was given in the
late stage than in the early stage. It was found that the photoinhibition is
mediated by both the phyA and the phyB in the late stage but predominantly by
phyB in the early stage. Consistent with many other reported responses, the photo
inhibition in the phyA mutant, which was observed in the early and late
developmental stages and is thought to be mediated mainly by phyB, occurred in
the low-fluence range (10(1)-10(3) micromol m(-2)) of R and was far-red-light
(FR)-reversible; the photo-inhibition in the phyB mutant, which was observed in
the late developmental stage and is thought to be mediated mainly by phyA,
occurred in the very-low-fluence range (10(-2)-10(0) micromol m(-2)) and was FR
irreversible. The action spectra (350-800 nm at 50 nm intervals) obtained at the
two developmental stages using phyA and phyB mutants indicated that both the phyB
mediated low-fluence response and the phyA-mediated very-low-fluence response
have a major peak at 650 nm and a minor peak at 400 nm.
PMID- 17029496
TI - Energy transfer from chemically attached rhodamine 101 to adsorbed methylene blue
on microcrystalline cellulose particles.
AB - Rhodamine 101 (R101) was chemically attached onto microcrystalline cellulose and
methylene blue (MB) was adsorbed to a sample bearing nearby 6 x 10(-7) mol R101
(g cellulose)(-1). The system was studied by reflectance and emission
spectroscopy in the solid state. R101 shows no aggregation in these conditions
and, while pure MB builds up dimers on cellulose even at 2 x 10(-8) mol g(-1), in
the presence of R101 no evidence on selfaggregation or heteroaggregation is found
up to around 10(-6) mol g(-1). No exciplex formation is found as well. The
overall fluorescence quantum yield measured on thick layers, once re-absorption
effects are accounted for, amounts to 0.80 +/- 0.07 for pure R101 and decreases
steadily on increasing the concentration of MB. Results demonstrate the
occurrence of radiative and nonradiative singlet energy transfer from R101 to MB.
For thick layers of particles, the combined effect of both kinds of energy
transfer amounts to nearly 80% at the highest acceptor concentration, while
nonradiative transfer reaches 60% both for thin and optically thick layers. The
dependence of nonradiative energy transfer efficiencies on the acceptor
concentration is analyzed and the origin of departures from Forster behavior at
low acceptor concentration is discussed.
PMID- 17029497
TI - Inhibition of return and negative priming by persons with and without mental
retardation.
AB - Persons with and without mental retardation who were matched on CA took part in
three tasks: an inhibition of return task, a location negative-priming task, and
an identity negative-priming task. Having participants perform all three tasks
allowed us to correlate performance among the tasks and assess the various
relationships among performance measures on negative priming and inhibition of
return. The participants with mental retardation did not exhibit negative priming
of identity. However, they did exhibit negative priming of location and
inhibition of return. The participants without mental retardation exhibited all
three effects. A different pattern of correlations was observed for the
participants with and those without mental retardation. Possible reasons for this
difference are discussed.
PMID- 17029499
TI - Broad cognitive abilities of children with mental retardation: an analysis of
group and individual profiles.
AB - Group and individual broad ability profiles of children with mental retardation
and a matched sample of children with average achievement was investigated
through use of the 7 Cattell-Horn-Carroll (CHC) factor clusters from the Woodcock
Johnson III Tests of Cognitive Abilities. Results indicate that, as a group, the
ranked performance of the children with mental retardation on the CHC factor
clusters was largely consistent with the clusters' g loadings. When compared to
average-achieving matches, the children with mental retardation scored lower on
all CHC factor clusters, but the groups displayed different patterns of
performance. Despite normative deficiencies in IQs, children with mental
retardation demonstrated a wide range of performance across measures.
Implications for assessment and diagnosis are discussed.
PMID- 17029498
TI - Longitudinal analysis of the impact and cost of person-centered planning for
people with intellectual disabilities in England.
AB - Person-centered planning is central to United Kingdom policies regarding the
support of people with intellectual disabilities. However, little evidence exists
on the impact or cost of introducing person-centered planning. We examined the
efficacy, effectiveness, and costs of introducing person-centered planning for 93
people with intellectual disabilities over 2 years across four localities in
England. A person-centered plan was successfully developed for 65 people. Little
change was apparent prior to introducing person-centered planning. After its
introduction, modest positive changes were found in the areas of social networks;
contact with family; contact with friends; community-based activities; scheduled
day activities; and choice. The direct training and support cost of introducing
person-centered planning was $1,202 per participant; indirect costs were
negligible.
PMID- 17029500
TI - Interpreting kappa in observational research: baserate matters.
AB - Kappa (Cohen, 1960) is a popular agreement statistic used to estimate the
accuracy of observers. The response of kappa to differing baserates was examined
and methods for estimating the accuracy of observers presented. Results suggest
that setting a single value of kappa as "minimally acceptable" (i.e., a criterion
value) is not useful in ensuring adequate accuracy of observers. Instead,
researchers should use the best estimate of the true baserate of the target
behavior and the obtained kappa to estimate the accuracy of observers.
Investigators can then compare the estimated accuracy of observers to a
preselected criterion level. Guidelines are given for selecting a criterion
accuracy level.
PMID- 17029501
TI - Effects of social stimuli on laughing and smiling in young children with Angelman
syndrome.
AB - The effects of social stimuli present and absent on laughing and smiling in 2
young children with Angelman syndrome were assessed via a multielement design.
Results indicated that laughing and smiling for either child was unaffected by
the social stimuli assessed in the social interaction condition. Results are
discussed in terms of the effects of biological variables and environmental
stimuli on children with specific genetic disorders across the lifespan.
PMID- 17029502
TI - Matching-to-sample assessment of stimulus overselectivity in students with
intellectual disabilities.
AB - A delayed matching-to-sample task with multiple sample stimuli was used to
evaluate stimulus overselectivity in 70 individuals attending residential special
education schools. A Mental Age Equivalent score (MAE) was obtained for each
student using the Peabody Picture Vocabulary Test. Twenty-one participants failed
to complete matching-to-sample pretests (mean MAE = 3.70 years). Results on the
multiple-sample test for the remaining 49 participants indicated no
overselectivity for 14 students (mean MAE = 7.44 years) and were consistent with
overselectivity for 35 students (mean MAE = 5.28 years). Performances of students
with overselectivity were more variable than those with no overselectivity. The
MAE scores were related to both matching-to-sample performance and stimulus
overselectivity.
PMID- 17029504
TI - Lip shape and position in Class II division 2 malocclusion.
AB - OBJECTIVE: To determine whether differences exist in the shape and position of
the lips between Class II division 2 and Class I malocclusions. MATERIALS AND
METHODS: Lateral cephalometric radiographs of subjects with Class II division 2
(n = 30) and Class I (n = 30) incisor relationships were scanned at 300 dpi to
produce digital images. These were subsequently digitized in random order. Twenty
one landmarks characterizing the upper and lower lips and the maxillary and
mandibular central incisors were digitized. Procrustes algorithms optimally
superimposed the landmark configurations to standardize size, location, and
orientation. Discriminant analysis of the principal components of shape
determined the differences between the Class II division 2 and Class I groups.
RESULTS: The shape and position of the upper and lower lips differed
significantly between the Class II division 2 group and the Class I group (P <
.001). Principal component (PC) 1 (46% of the variance) involved an increase in
the thickness of the upper and lower lips in the Class II division 2 group. PC2
(11% of the variance) was characterized by a relatively higher lip line in the
Class II division 2 group. CONCLUSIONS: The shape and position of the lips differ
between Class II division 2 and Class I malocclusions.
PMID- 17029505
TI - Predictive factors of vertical bone depth in the paramedian palate of
adolescents.
AB - OBJECTIVE: To determine whether a relationship exists between the vertical bone
depth in the paramedian palate (PP) of growing patients and age, gender, and
palatal morphology. Clinically detectable traits may decrease the need for
further imaging prior to implant placement for orthodontic anchorage. MATERIALS
AND METHODS: Cone beam computed tomagraphic scans (Newtom-9000, Verona, Italy)
were acquired in 183 orthodontic patients (10-19 years old). Vertical bone depth
was measured at nine unilateral locations in the PP of each subject. Measurements
were analyzed with univariate and multivariate statistical tests. RESULTS:
Significant variability in the bone thickness was found among locations and among
subjects. Male subjects had significantly greater mean bone thickness in six of
the nine locations measured, showing a mean of 1.22 mm more vertical bone than
females showed at these locations. Age and palatal measurements did not
demonstrate a clinically useful relationship with bone depth. CONCLUSIONS: Age
and palatal morphology are not valid predictors of bone height in the PP. Because
of the large variability of bone thickness in this region, computed tomographic
imaging remains valuable prior to paramedian implant placement in growing
individuals. The paramedian palate presents a promising region for palatal
implant placements when the midpalatal suture is to be avoided.
PMID- 17029506
TI - Correlations between rapid maxillary expansion (RME) and the auditory apparatus.
AB - OBJECTIVE: To evaluate the effects of rapid maxillary expansion (RME) on
conductive hearing loss and maxillary constriction. MATERIALS AND METHODS: A
total of 25 subjects (15 girls and 10 boys, aged between 6 years 8 months to 8
years 2 months) with conductive hearing loss and maxillary constriction were
studied. Audiogram, tympanogram, and video-otoscopy were used to investigate the
anatomical and physiological modifications of the bony and muscular structure of
the maxilla and the auditory apparatus. The records were taken before maxillary
expansion (T0), after expansion (7-14 days; T1), and after the retention period
(8 months after expansion; T2). RESULTS: After expansion, the audiometric records
indicated an improvement in hearing levels for higher frequencies but not for
lower ones. After the retention period, there was a functional improvement in all
patients for all frequencies. The recovery of the tympanic membrane's elasticity
occurred only after retention, as shown by the standard model tympanogram, which
was still flat after expansion. CONCLUSIONS: The auditory function in patients
with conductive hearing loss may be corrected through correction of the palatal
anatomy, which influences the muscular function of the tubal ostia and allows a
normal activity of the tympanic membrane and the auditory apparatus. Positive
effects on conductive hearing loss are possible additional benefits of RME
treatment, but this does not indicate that patients with conductive hearing loss
without an accompanying maxillary constriction should consider this as a
treatment approach.
PMID- 17029507
TI - Nonsurgical rapid maxillary expansion effects on craniofacial structures in young
adult females. A bone scintigraphy study.
AB - OBJECTIVE: To evaluate the skeletal effects of nonsurgical rapid maxillary
expansion (RME) on craniofacial structures with bone scintigraphy in young adult
female subjects. MATERIALS AND METHODS: The material of the present study
consists of scintigraphic records taken from 17 early adult females treated with
RME. All patients had a bilateral posterior crossbite, transverse maxillary
deficiency, deep palatal vault, and dental crowding at the beginning of the
treatment. The age range of the patients was 16.1 to 18.8 years, and the mean age
was 17.3 +/- 0.86 years. Bone scintigraphy records were obtained before RME (T1),
during the splitting of the midpalatal suture (T2), and after the end of active
widening period (T3). Repeated measure analysis of variance was used to assess
the differences between the periods. In addition, Bonferroni multiple comparison
tests were applied to the measurements at which F values were found to be
statistically significant. RESULTS: According to the statistical analysis,
significant activity changes were found in all regions studied and in all slices.
The metabolic activity in all regions showed significant increases up to the
separation of the midpalatal suture (T1-T2), whereas the metabolic activity
exhibited a remarkable decrease (T2-T3) after the opening of the midpalatal
suture. CONCLUSIONS: Scintigraphic records revealed an increase in the regions of
interest scores during RME in all regions and all slices. Therefore, it can be
speculated that RME has had not only dental effects but also skeletal effects on
young adult patients.
PMID- 17029508
TI - Dental maturation in short and long facial types. Is there a difference?
AB - OBJECTIVE: The purpose of this investigation was to study the relationship
between vertical skeletal growth pattern and dental maturation in children with
long or short anterior facial height. MATERIALS AND METHODS: The sample consisted
of the records of 312 Dutch children (153 boys and 159 girls, aged 9-12.9 years,
with a mean chronological age of 11.3 years). The subjects were selected
according to their lower anterior facial height as a percentage of the total
facial height. Two groups, one with long and the other with short anterior facial
height, were formed for further comparison. Dental age, according to Demirjian's
dental maturity score, was determined for each subject. The power of the study
was 79% (2-sided test) and 87% (1-sided test). RESULTS: There was no
statistically significant difference in dental age score between the two extreme
groups. The subjects with short anterior facial height demonstrated a slight
tendency toward more advanced dental age. CONCLUSIONS: The difference in dental
age between long and short facial types is not big enough to be clinically
relevant.
PMID- 17029509
TI - Measuring adult facial morphology in three dimensions.
AB - OBJECTIVES: The aim of this study is to evaluate the reliability of measuring
three-dimensional soft tissue morphology using a laser imaging system. DESIGN:
Prospective clinical trial. MATERIALS AND METHODS: Thirty-eight adult subjects,
mean age 24.5 years, were analyzed for soft tissue changes at baseline (T1) and
at 1 week (T2) using two commercially available Minolta Vivid 900 (Osaka, Japan)
laser scanning devices assembled as a stereopair. Left and right images were
merged to form the whole face, and these images were superimposed to assess the
errors between the two faces at T1 and at T2. RESULTS: The results showed that
the mean shell deviations for left and right scans at T1 were 0.32 +/- 0.08 mm
and 0.30 +/- 0.09 mm for males and females, respectively. The mean shell
deviations for left and right scans at T2 were 0.34 +/- 0.08 mm and 0.32 +/- 0.09
mm for males and females, respectively. The mean difference of the merged
composite faces superimposed at T1 and T2 was 0.37 +/- 0.07 mm and 0.35 +/- 0.09
mm for males and females, respectively. Paired t-tests revealed that the mean
difference of 0.02 mm was statistically insignificant (P > .05). The
reproducibility error was 0.7 and 0.8 mm for females and males, respectively,
when a tolerance of 90% was imposed on the aligned faces. CONCLUSIONS: Capturing
soft tissue morphology of the face, using the technique described, is clinically
reproducible within 1 week of the initial records.
PMID- 17029510
TI - Relationship between thoracic, lordotic, and pelvic inclination and craniofacial
morphology in adults.
AB - OBJECTIVE: To analyze the correlation ratios between the spinal posture
(thoracic, lordotic, and pelvic inclination) and the craniofacial morphology.
MATERIALS AND METHODS: The sample consisted of 53 healthy adults (32 women, 21
men; mean age 24.6 years). Six angular skeletal measurements (facial axis,
mandibular plane angle, inner gonial angle, lower facial height, facial depth,
and maxilla position) were determined based on the analysis of lateral head
cephalographs. Rasterstereography was used for a precise reconstruction of the
back sagittal profile. From the profile parameters, the upper thoracic
inclination, the thoracic angle, the lordotic angle, and the pelvic inclination
were determined. The correlations to the craniofacial morphology were calculated
by means of the Pearson and Mann-Whitney U-test. RESULTS: Significant
correlations could be obtained with respect to the facial axis and the lordotic
angle, the facial axis and the pelvic inclination, the inner gonial angle and the
lordotic angle, the inner gonial angle and the pelvic inclination, the mandibular
plane angle and the lordotic angle, the mandibular plane angle and the pelvic
inclination, as well as the facial depth and the pelvic inclination. CONCLUSIONS:
In the case of postural disorders of the back shape, an interdisciplinary
treatment approach seems to be of clinical value. Further prospective studies are
necessary to prove how changes in craniofacial parameters can affect the postural
balance of an individual.
PMID- 17029511
TI - Mandibular growth during adolescence.
AB - OBJECTIVE: To evaluate the mandibular growth of whites according to Fishman's
method. MATERIALS AND METHODS: Eighty-five subjects, 9 to 18 years of age, were
selected from the files of the Department of Orthodontics, Pontificia
Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil. Patients were
evaluated at two time points. At T1, they had a lateral head film and a hand
wrist radiograph and at T2, a lateral head film. The interval between T1 and T2
was 5 to 24 months. Subjects presented a Class I or II skeletal pattern and were
divided into three groups according to Fishman's method: group I, in an
accelerating growth velocity phase; group II, in peak of growth velocity phase;
and group III, in decelerating growth velocity phase. The cephalograms were
manually traced and cephalometric points digitalized into DentoFacial Planner
Plus 2.0. The absolute growth amount was adjusted to obtain an annual growth rate
(mm/y). The annual growth rate was compared between sexes, between individuals
with Class I or II skeletal patterns, and among the three groups. RESULTS:
Mandibular annual growth rate in puberty was 2.16 mm for the mandibular body
length, 3.16 mm for the ramus height, and 4.31 mm for the mandibular length. The
results did not show significant differences between sexes, skeletal patterns,
and groups, although there was a tendency for growth acceleration in group II.
CONCLUSIONS: There is great individual variation in mandibular linear growth.
PMID- 17029512
TI - Customized three-dimensional computational fluid dynamics simulation of the upper
airway of obstructive sleep apnea.
AB - OBJECTIVE: To use computer simulations to describe the role of fluid dynamics in
the human upper airway. MATERIALS AND METHODS: The model was constructed using
raw data from three-dimensional (3-D) computed tomogram (CT) images of an
obstructive sleep apnea (OSA) patient. Using Bionix software (CantiBio Inc.,
Suwon, Korea), the CT data in DICOM format was transformed into an anatomically
correct 3-D Computational fluid dynamic (CFD) model of the human upper airway.
Once constructed, the model was meshed into 725,671 tetra-elements. The solution
for testing was performed by the STAR-CD software (CD adapco group, New York,
NY). Airflow was assumed to be turbulent at an inspiration rate of 170, 200, and
230 ml/s per nostril. The velocity magnitude, relative pressure, and flow
distribution was obtained. RESULTS: High airflow velocity predominated in medial
and ventral nasal airway regions. Maximum air velocity (15.41 m/s) and lowest
pressure (negative 110.8 Pa) were observed at the narrowest portions of the
velopharynx. Considering differences in model geometry, flow rate, and reference
sections, when airflow patterns in nasal cavity were compared, our results were
in agreement with previous data. CONCLUSIONS: CFD analyses on airway CT data
enhanced our understanding of pharyngeal aerodynamics in the pathophysiology of
OSA and could predict the outcome of surgeries for airway modification in OSA
patients.
PMID- 17029513
TI - Linear and angular filipino cephalometric norms according to age and sex.
AB - OBJECTIVE: To quantify relevant cephalometric parameters for Filipinos according
to age and sex. MATERIALS AND METHODS: A total of 157 Filipino subjects (78
males, 79 females) who fulfilled specific criteria were selected from elementary,
high school, and college students affiliated with Manila Central University. They
were divided into comparison groups (GI, GII, GIII, and GIV) on the basis of
chronological age and sex. Lateral cephalograms were taken for all subjects, and
the mean and standard deviation for each parameter was recorded and compared
among groups. RESULTS: The male group had a longer anterior cranial base (S-N),
total facial height (N-Me), longer lower anterior facial height (N-ANS), longer
ramus height (Cd-Go), longer lower posterior dentoalveolar height (Mo-Mi'), and
total mandibular length (Gn-Cd) than the female group. All these linear
measurements were statistically significantly different between males and females
in GI, GIII, and GIV. On the other hand, SNB angle showed significant differences
(P = .0271) in GIV only. In the lower third of the face, significant opposite
tendencies were found in GIV. The female group showed a clockwise rotation,
whereas the male counterpart had a counterclockwise rotation of the mandibular
plane. The denture pattern of both groups was characterized by a proclination of
both lower incisor (Ii to MP) and upper incisor (Is to SN). CONCLUSIONS:
Convexity due to dentoalveolar protrusion is the naturally occurring facial
profile for Filipinos. The adult females showed steeper mandibular and occlusal
plane angles than the male samples.
PMID- 17029514
TI - Spectrum and management of dentofacial deformities in a multiethnic Asian
population.
AB - OBJECTIVE: The aim of this retrospective study is to investigate the spectrum and
management of dentofacial deformities in a multiethnic Asian community. MATERIALS
AND METHODS: Over a period of 3 years (2001 to 2003), 212 patients with
dentofacial deformities who had undergone orthognathic surgery in a national
tertiary specialist center in Singapore were reviewed. Patients with cleft lip
and palate or syndromes were excluded. RESULTS: The mean age (range: 16 to 58
years) of the patients was 24.0 years (SD 6.4) and the ratio of female to male
was 1.3:1. The predominant ethnic group was Chinese (91.5%). The majority of the
patients had skeletal Class III pattern (68%). Asymmetry was diagnosed in 36% of
all cases and in 48% of skeletal Class III cases. Vertical maxillary excess was
diagnosed in 21% of all cases and in 47% of skeletal Class II cases. Bimaxillary
surgery involving LeFort and bilateral sagittal split osteotomies was performed
in 84% of skeletal Class III cases and in 73% of all cases. Segmental osteotomy
and genioplasty were performed in 41% of the cases. CONCLUSIONS: The findings
suggest that the majority of the patients were young Chinese adults with two-jaw
deformities requiring bimaxillary surgeries with genioplasty or segmental
osteotomy. This finding may reflect the greater severity of dentofacial
deformities in patients in the Asian community.
PMID- 17029515
TI - Midfacial morphology in adult unoperated complete unilateral cleft lip and palate
patients.
AB - OBJECTIVE: To examine lateral cephalometric radiographs of adult unoperated cleft
lip and palate patients for the purpose of clarifying whether maxillary
deficiencies observed in treated cleft patients result from intrinsic defects or
surgical intervention early in life. MATERIALS AND METHODS: This retrospective
study examined lateral cephalograms of 30 adult patients with nonsyndromic
complete unilateral cleft lip and palate (CUCLP). The lateral cephalograms were
traced and evaluated for size and position of the cranial base, maxilla,
maxillary dentition, mandible, and mandibular dentition as well as for vertical
relationships. Comparisons with 30 adult noncleft individuals were made. RESULTS:
In unoperated adult cleft lip and palate patients, the cranial base angle was
increased with the anterior cranial base reduced in length. The maxilla was found
to be normal in size and somewhat prognathic in position. Both the maxillary and
mandibular incisors were relatively upright. The mandible was smaller in size and
posteriorly positioned. CONCLUSIONS: The potential for normal growth of the
maxilla exists in patients with CUCLP. It is likely that disturbances of
maxillary growth in surgically operated cleft patients are related primarily to
the surgical intervention.
PMID- 17029516
TI - Occlusal development in children of African American descent. Types of terminal
plane relationships in the primary dentition.
AB - OBJECTIVE: To compare the types and depths of the terminal plane relationships
(mesial step, distal step, and flush) in the primary dentitions of African
American (AA) and European (E) children. MATERIALS AND METHODS: A convenience
sample of 189 African American children (103 males and 86 females) was compared
to a historical sample of 61 European children (39 males and 22 females, age
range 2.1 to 5.2 years, mean age of 4.1 years). Plaster dental casts were
analyzed for both samples. Terminal plane depth (TPD) was defined as the
anteroposterior distance (APD) between the distal surfaces of the maxillary and
mandibular second primary molars of dental casts registered in centric occlusion.
Sample differences were evaluated using a 2-sample independent group t-test.
RESULTS: Eighty-nine percent of African American children and 63% of European
children exhibited a mesial step terminal plane. The average APD of the mesial
step in African American children was 1.29 mm compared to 1.13 mm in European
children, but this was not statistically significant (P = .18). The samples
differed significantly (P = .001) in the average APD distal step relationship
(AA, 1.08 mm vs E, 2.26 mm). The prevalence of distal step relationships was
lower in African American children (5%) compared to European children (16%).
African American children had a lower prevalence of flush terminal plane (6%)
compared to European children (21%). CONCLUSIONS: In African American children as
in European children, a mesial step, rather than a flush terminal plane, is the
norm for the completed primary dentition.
PMID- 17029517
TI - Comparison of Doppler sonography to magnetic resonance imaging and clinical
examination for disc displacement.
AB - OBJECTIVE: To compare electronic devices advocated as an aid in the diagnosis of
disc displacement (DD) of the temporomandibular joint. MATERIALS AND METHODS:
Ninety-five joints (48 subjects, 36 females and 12 males, mean age = 33.3 years,
SD +/- 11.9) were evaluated in this study using magnetic resonance imaging (MRI),
clinical examination, and Doppler sonography. All subjects had bilateral MRI
scans in the sagittal closed and opened and coronal closed positions. RESULTS:
When the clinical and the Doppler diagnoses for all subjects were compared with
the MRI diagnosis, there was a sensitivity of 73% and 90% and a specificity of
70% and 49%, respectively. When the clinical and the Doppler diagnoses for
asymptomatic volunteers were compared with the MRI, there was a sensitivity of 0%
and 100% and a specificity of 100% and 56%, respectively. For the symptomatic
patients, there was a sensitivity of 80% and 89% and a specificity of 48% and
45%, respectively. CONCLUSIONS: The relatively low number of false-negative
examinations suggests that Doppler is useful for ruling out DD and may be
especially useful in symptomatic patients. Unfortunately, the specificity was
low, producing many false-positive examinations.
PMID- 17029518
TI - Interleukine-1beta and tumor necrosis factor-alpha levels in the human gingival
sulcus during orthodontic treatment.
AB - OBJECTIVE: To test whether interleukine 1beta (IL-1beta) and tumor necrosis
factor-alpha (TNF-alpha) levels differ from each other in different treatment
levels. MATERIALS AND METHODS: Eighteen patients, nine female and nine male (aged
16-19 years; mean 17.4 +/- 1.8 years), participated in this study. Each subject
underwent a session on professional oral hygiene and received oral hygiene
instructions. Two months later, a fixed orthodontic appliance was placed. The
patients were seen at baseline, at days 7 and 21 and at the 3rd and 6th month as
the leveling of the teeth occurred. Records of the baseline scores for the
distalization forces were taken at the 6th month. Days 7 and 21 after 6 months of
treatment were also recorded. RESULTS: There were increases in the volume of
gingival crevicular fluid (GCF) and in the concentrations of IL-1beta and TNF
alpha. CONCLUSIONS: Leveling and distalization of the teeth evoke increases in
both the IL-1 and TNF-alpha levels that can be detected in GCF.
PMID- 17029519
TI - Orthodontic bonding with varying curing time and light power using an argon
laser.
AB - OBJECTIVE: To test the effects of curing time and light intensity on the shear
bond strength of adhesive composites for stainless-steel orthodontic brackets.
MATERIALS AND METHODS: An argon laser at four different power settings (100, 150,
200, and 250 mW) and four different exposure times (5, 10, 15, and 20 seconds)
was used to bond adhesive-precoated (APC) stainless-steel incisor brackets to the
facial surfaces of 154 bovine incisors. The shear bond strength of each specimen
in 16 randomly divided groups was randomly tested to failure using an Instron
universal testing machine. Each mode of failure was described using the adhesive
remnant index (ARI). RESULTS: The ARI scoring system showed that the location of
bond failure did not differ significantly in relation to exposure time (P = .40).
However, the location of bond failure was significantly different in relation to
light power (P = .03). CONCLUSIONS: A short exposure time and a low power setting
produce shear bond strengths equivalent to those produced by longer exposure
times and higher power settings.
PMID- 17029520
TI - Fluoride-releasing adhesive and antimicrobial self-etching primer effects on
shear bond strength of orthodontic brackets.
AB - OBJECTIVE: To determine whether the combination of a new antimicrobial primer and
a fluoride-releasing adhesive will affect the shear bond strength (SBS) and the
bracket/adhesive failure mode. MATERIALS AND METHODS: A total of 120 extracted
human teeth were randomly divided into three groups of 40 specimens each (20
incisors, 20 premolars). Transbond XT was used in group 1, a fluoride-releasing
adhesive (Kurasper F) was used in group 2, and a new antimicrobial self-etching
primer (Clearfil Protect Bond) was applied in combination with Kurasper F in
group 3. A universal testing machine was used to determine the SBS, and the
adhesive remaining after debonding was assessed. RESULTS: No enamel fractures
were detected in any of the specimens. SBS values for incisors and premolars were
11.40 +/- 4.65 MPa and 10.37 +/- 3.36 MPa in group 1, 14.50 +/- 4.22 MPa and
13.06 +/- 5.13 MPa in group 2, and 14.79 +/- 4.10 MPa and 14.60 +/- 3.55 MPa in
group 3. Statistically significant difference (P = .001) was found in the
premolars in group 3 revealing the highest mean SBS. Significantly lower adhesive
remnant index (ARI) values (median ARI value of 1) were detected in group 3 when
compared with groups 1 and 2. CONCLUSIONS: Considering the acceptable bond
strength and the mode of failure, the combination of the new antimicrobial primer
with the fluoride-releasing adhesive is recommended for clinical use.
PMID- 17029521
TI - Shear bond strength of metal brackets on enamel.
AB - OBJECTIVE: To compare the shear bond strength of different metal orthodontic
brackets. MATERIALS AND METHODS: Five types of orthodontic metal brackets were
selected (S1, Victory Series, 3M Unitek, Monrovia, Calif; S2, Mini Dyna-Lock, 3M
Unitek; S3, Mini Sprint, Forestadent, Pforzheim, Germany; S4, Topic, Dentaurum,
Inspringen, Germany; and S5, equilibrium 2, Dentaurum). Brackets were bonded on
enamel surfaces of bovine incisors (Transbond XT, 3M Unitek) and were tested for
shear bond strength with an Instron universal testing machine (Instron Corp,
Canton, Mass). Data obtained in newtons and megapascals were analyzed with
descriptive statistics and with analysis of variance and Tukey honestly
significant difference (HSD) tests. The adhesive fracture site was classified
with the adhesive remnant index (ARI). RESULTS: All the specimens tested had
shear bond strength adequate to resist orthodontic forces. S5 showed
significantly greater bond strength when compared with the other samples, except
for S1. S1, S3, and S5 showed a significantly greater bonding force. The ARI
index demonstrated a large variability. Retentive structure of S1, S3, and S5 had
equal validity. The enlargement of the retentive surface enhances adhesion but
affects the adaptability to surface irregularity of the enamel, increasing the
risk of fracture at the interface with the bracket. CONCLUSIONS: The results of
this study suggest that probably the retentive base extension can be lower than 7
mm2 proposed in previous studies as the minimal area.
PMID- 17029522
TI - Effects of silica coating and silane surface conditioning on the bond strength of
metal and ceramic brackets to enamel.
AB - OBJECTIVE: To evaluate the effect of tribochemical silica coating and silane
surface conditioning on the bond strength of metal and ceramic brackets bonded to
enamel surfaces with light-cured composite resin. MATERIALS AND METHODS: Twenty
metal and 20 ceramic brackets were divided into four groups (n = 10 for each
group). The specimens were randomly assigned to one of the following treatment
conditions of the metal and ceramic brackets' surface: (1) tribochemical silica
coating combined with silane and (2) no treatment. Brackets were bonded to the
enamel surface on the labial and lingual sides of human maxillary premolars (20
total) with a light-polymerized resin composite. All specimens were stored in
water for 1 week at 37 degrees C and then thermocycled (5000 cycles, 5 degrees C
to 55 degrees C, 30 seconds). The shear bond strength values were measured on a
universal testing machine. Student's t-test was used to compare the data (alpha =
0.05). The types of failures were observed using a stereomicroscope. RESULTS:
Metal and ceramic brackets treated with silica coating with silanization had
significantly greater bond strength values (metal brackets: 14.2 +/- 1.7 MPa, P <
.01; ceramic brackets: 25.9 +/- 4.4 MPa, P < .0001) than the control groups
(metal brackets: 11.9 +/- 1.3 MPa; ceramic brackets: 15.6 +/- 4.2 MPa). Treated
specimens of metal and ceramic exhibited cohesive failures in resin and adhesive
failures at the enamel-adhesive interface, whereas control specimens showed mixed
types of failures. CONCLUSIONS: Silica coating with aluminum trioxide particles
coated with silica followed by silanization gave higher bond strengths in both
metal and ceramic brackets than in the control group.
PMID- 17029523
TI - Six-month bracket survival with a self-etch adhesive.
AB - OBJECTIVE: To evaluate, over a 6-month period, the clinical performance of a self
etch adhesive (Transbond Plus Self-Etching) compared with a conventional adhesive
that uses the etch and rinse approach (Transbond XT). MATERIALS AND METHODS: One
operator, using the straight-wire technique, placed 567 metallic brackets in 30
patients (age range 12-18 years) such that homologous teeth from the same arch
received different materials. The brackets were bonded following the
manufacturer's instruction except for the fact that the self-etch system was
brushed for a longer time than recommended (10-15 seconds). The failure modes
were visually classified into three modes: adhesive-enamel, adhesive-bracket, and
cohesive failure. The survival rate of the brackets was estimated by Kaplan-Meier
and log-rank test (P < .05). RESULTS: The failure rates of the conventional and
self-etch [corrected] adhesives were 10.6% and 7.4%, respectively. The failure
rate of the conventional system was 0.43 [corrected] times greater than that of
the self-etch system. The self-etch adhesive showed a higher survival rate
compared with the conventional system (P < .05). Most of the failures were
cohesive and at the adhesive-enamel surface. No difference in the fracture
debonding mode was observed for the materials. CONCLUSIONS: These findings
indicate that the self-etch Transbond Plus Self-Etching can be safely used for
orthodontic brackets because it provides higher survival rates than does the
conventional Transbond XT.
PMID- 17029524
TI - Quantitative determination of adhesion patterns of cariogenic streptococci to
various orthodontic adhesives.
AB - OBJECTIVE: To investigate the adhesion of various cariogenic streptococci to
orthodontic adhesives. MATERIALS AND METHODS: Five light-cure orthodontic
adhesives (one fluoride-releasing composite, three non-fluoride-releasing
composites, and one resin-modified glass ionomer cement) were used. The adhesive
type, bacterial strain, incubation time, and saliva coating were studied. Thirty
specimens of each adhesive were incubated with unstimulated whole saliva or
phosphate-buffered saline for 2 hours. Binding assays were then performed by
incubating tritium-labeled streptococci with the adhesives for 3 or 6 hours.
RESULTS: The results showed a characteristic adhesion pattern according to the
type of bacterial strains used. Streptococcus mutans LM7 showed the highest
amount of adhesion, whereas S sobrinus B13 showed the lowest amount of adhesion.
The cariogenic streptococci adhered to the glass ionomer significantly more than
to the composites, whereas there was no significant difference in the adhesion
amount among the four composites. The extended incubation time significantly
increased bacterial adhesion. However, saliva coating did not significantly alter
adhesion patterns of cariogenic streptococci. CONCLUSIONS: This study suggests
that cariogenic streptococci can adhere diversely according to adhesive type and
that the adhesion of the cariogenic streptococci is not influenced by its
fluoride-releasing properties.
PMID- 17029525
TI - Uprighting partially impacted permanent second molars.
AB - Impaction of the lower second molar is not a common problem, but it is very
challenging for both orthodontist and oral surgeon. Treatment options depend on
the degree of tooth inclination, the position of the third molars, and the
desired type of movement, which may be surgical and/or orthodontic in nature. A
good treatment alternative is surgical uncovering with orthodontically-assisted
eruption. A case of successful uprighting using a 0.017 x 0.025-inch titanium
molybdenum alloy (TMA) tip-back cantilever is presented. Different aspects of
uprighting impacted second molars are discussed in light of the literature. The
iatrogenic character of lower second molar impaction is emphasized.
PMID- 17029526
TI - Cephalometric facial soft tissue changes with the twin block appliance in Class
II division 1 malocclusion patients. A systematic review.
AB - OBJECTIVE: To evaluate facial soft tissue changes after the use of the twin block
appliance in Class II division 1 malocclusion patients. MATERIALS AND METHODS:
Several electronic databases (PubMed, MEDLINE, MEDLINE In-Process & Other Non
Indexed Citations, Cochrane databases, EMBASE, Web of Science, and LILACS) were
searched with the help of a senior health-sciences librarian. Abstracts that
appeared to fulfill the initial selection criteria were selected by consensus,
and the original articles were retrieved. The article references were hand
searched for possible missing articles. Clinical trials that assessed facial soft
tissue changes with the use of the twin block appliance without any surgical
intervention or syndromic characteristics were considered. A comparable untreated
control group was required to factor out normal growth changes. RESULTS: Two
articles fulfilled the selection criteria and quantified facial soft tissue
changes. Although some statistically significant changes in the soft tissue
profile were found, the magnitude of the changes may not be perceived as
clinically significant. Changes produced in the upper lip seem to be
controversial, although the study with sounder methodological quality did not
report significant changes. No change in the anteroposterior position of the
lower lip and the soft tissue menton or improvement of the facial convexity was
found. CONCLUSIONS: Three-dimensional quantification of the soft tissue changes
is required to overcome current limitations in our understanding of the soft
tissue changes obtained after the use of the twin block appliance in Class II
division 1 malocclusion patients.
PMID- 17029527
TI - Lower incisor retraction with a modified corticotomy.
AB - This case report demonstrates the orthodontic treatment facilitated with a new
conservative corticotomy technique to shorten the treatment time during lower
incisor retraction. The patient was a 22-year-old woman with protrusive profile,
severe anterior crowding, an anterior crossbite, and Class III dental
relationship. Orthodontic treatment consisted of the extraction of four first
premolars with maximum anchorage. A modified corticotomy technique, in which the
lingual vertical and subapical horizontal cuts were eliminated, was combined with
orthodontic therapy for the retraction of the lower anterior teeth. Corticotomy
facilitated orthodontics dramatically reduced the treatment time without any
adverse effects on the periodontium and the vitality of the teeth. The main
advantages of this modified corticotomy technique were the elimination of the
lingual cuts and flap, the reduction of surgery time, and minimum discomfort to
the patient. At the end of active orthodontic therapy, balanced occlusion and
facial esthetics were achieved.
PMID- 17029528
TI - Familial occurrence of nonsyndromal multiple supernumerary teeth. A rare
condition.
AB - The occurrence of multiple supernumerary teeth is a rare phenomenon and is often
found in association with syndromes such as cleidocranial dysplasia, Gardners
syndrome, or cleft lip and palate. Only a few examples of nonsyndromal multiple
supernumerary teeth have been reported in the literature. There is a predilection
for the mandible and in the premolar area followed by the molar and anterior
regions. This article reports the presence of nonsyndromal multiple supernumerary
teeth involving both jaws in children and in their mothers. The clinical and
radiographic appearance of the anomalies and treatment modalities are discussed.
PMID- 17029529
TI - Skeletal characteristics and treatment outcome of five patients with Robin
sequence.
AB - OBJECTIVE: To examine the variation in the precise skeletal characteristics and
the treatment outcomes of five Japanese Robin sequence cases. MATERIALS AND
METHODS: The birth histories and orthodontic records of five Japanese Robin
sequence patients were collected and analyzed. RESULTS: All cases had a
retrognathic appearance with small SNA and SNB angles. They had significantly
steep mandibular planes with lingual tipped incisors in both arches. The gonial
angles in two cases were within the Japanese norm, whereas the remaining three
showed significantly enlarged angles. Moreover, all cases showed a significantly
shorter ramus length, but the mandibular body was short in only two cases. All
had moderate or severe crowding in both arches, and therefore extraction of
lateral dentition or lateral incisors was performed in conjunction with
orthodontic treatment. An edgewise multibracket appliance was placed, and labial
tipping of the lower incisors was performed in all cases. All obtained normal
functional occlusion after active treatment, but the retrognathic appearance
remained in most cases. CONCLUSIONS: The present cases with Robin sequence showed
variation in the gonial angle and mandibular body length, although all commonly
exhibited smaller SNA and SNB angles with significantly steep mandibular planes.
Significant labial tipping of the lower incisors was required during the active
treatment, and all cases finally obtained functional occlusion, indicating the
relatively good prognosis on the occlusion of this sequence.
PMID- 17029530
TI - Condylar asymmetry in bilateral posterior crossbite patients.
AB - OBJECTIVE: To investigate whether patients with bilateral posterior crossbite
have asymmetrically developed condyles. MATERIALS AND METHODS: The study group
consisted of 75 patients with bilateral posterior crossbite, and a control group
of 75 subjects with normal occlusion. Condylar, ramal, and condylar plus ramal
asymmetry values were computed for all of the subjects on orthopantomograms. Data
were analyzed statistically by means of paired t-test and Student's t-test.
RESULTS: The patients with bilateral posterior crossbite had more asymmetrical
condyles relative to the controls. However, there were no statistically
significant differences in condylar, ramal, or condylar plus ramal heights
between left and right sides in both the control and crossbite groups.
CONCLUSION: Patients with bilateral posterior crossbite can have asymmetrical
condyles and might be at risk for the development of future skeletal mandibular
asymmetries.
PMID- 17029531
TI - Microscrew anchorage in skeletal anterior open-bite treatment.
AB - OBJECTIVE: To evaluate the effectiveness of miniscrew anchorage for intrusion of
the posterior dentoalveolar region to correct skeletal open bite. MATERIALS AND
METHODS: The study was comprised of 12 patients (aged 14.3 to 27.2 years; mean
18.7 years) with anterior open bites. All the patients presented a Class II
skeletal pattern and excessive posterior growth. Self-drilling miniscrew implants
were inserted into the posterior midpalatal area and the buccal alveolar bone
between the lower molars. A transpalatal and a lingual arch were used to maintain
the molars on each side in order to avoid overrotation during intrusion. A force
of 150 g was applied to the microscrews on each side to intrude the posterior
teeth. Lateral cephalograms of all 12 patients were taken preintrusion and
immediately after completion of the intrusion. The cephalometric films were
measured and compared. RESULTS: The results showed that the anterior open bites
in 12 patients were all corrected in a mean of 6.8 months. Overbite increased by
a mean of 4.2 mm (P < .001), from -2.2 mm in preintrusion to 2.0 mm in
postintrusion. The maxillary and mandibular first molars were intruded for an
average of 1.8 mm (P < .001) and 1.2 mm (P < .001), respectively. The mandibular
plane angle was reduced by 2.3 degrees (P < .001), which led to a
counterclockwise rotation of the mandible with a significant decrease in the
anterior facial heights (mean of 1.8 mm; P < .001). CONCLUSION: Miniscrew
anchorage has the advantages of being a simpler procedure, being minimally
invasive, and requiring minimal patient cooperation.
PMID- 17029532
TI - Dental arch widths and mandibular-maxillary base width in Class III malocclusions
with low, average and high MP-SN angles.
AB - OBJECTIVE: To analyze the development of the dental arches and skeletal
mandibular-maxillary bases in untreated Class III malocclusions with low averages
and high mandibular plane angles in subjects aged 10 to 14. MATERIALS AND
METHODS: The records of 50 untreated Japanese girls with Class III malocclusions
at age 10 were selected from the files of patients pending orthodontic surgery.
The patients included those with low (< or =27 degrees), average (27 degrees
through 37 degrees) and high (>37 degrees) mandibular plane angles. The maxillary
skeletal base width, biantegonial width, and maxillary and mandibular intermolar
width were determined on posteroanterior cephalograms obtained at annual
intervals when subjects were between 10 and 14 years of age. The difference
between the maxillary and mandibular intermolar width was also calculated and
reported. RESULTS: All skeletal and dental transverse widths in the high-angle
group were significantly smaller than those in the low-angle group (P < .05) from
ages 10 to 14. On the other hand, the maxillary to mandibular molar difference
was the same for the three groups (P > .05) at each age. The deviations in molar
differences did increase from age 10 to age 14 in all three groups. CONCLUSION:
Mandibular plane angles might play a stronger role in the transverse skeletal
growth of the maxilla and the mandible than the transverse dental growth of the
maxilla and the mandible.
PMID- 17029533
TI - Long-term stability of orthodontic treatment and patient satisfaction. A
systematic review.
AB - OBJECTIVE: To evaluate morphologic stability and patient satisfaction at least 5
years after orthodontic treatment. MATERIALS AND METHODS: Published literature
was searched through the PubMed and Cochrane Library electronic databases from
1966 to January 2005. The search was performed by an information specialist at
the Swedish Council on Technology Assessment in Health Care. The inclusion
criteria consisted of a follow-up period of at least 5 years postretention;
randomized clinical trials, prospective or retrospective clinical controlled
studies, and cohort studies; and orthodontic treatment including fixed or
removable appliances, selective grinding, or extractions. Two reviewers extracted
the data independently and also assessed the quality of the studies. RESULTS: The
search strategy resulted in 1004 abstracts or full-text articles, of which 38 met
the inclusion criteria. Treatment of crowding resulted in successful dental
alignment. However, the mandibular arch length and width gradually decreased, and
crowding of the lower anterior teeth reoccurred postretention. This condition was
unpredictable at the individual level (limited evidence). Treatment of Angle
Class II division 1 malocclusion with Herbst appliance normalized the occlusion.
Relapse occurred but could not be predicted at the individual level (limited
evidence). The scientific evidence was insufficient for conclusions on treatment
of cross-bite, Angle Class III, open bite, and various other malocclusions as
well as on patient satisfaction in a long-term perspective. CONCLUSIONS: This
review has exposed the difficulties in drawing meaningful evidence-based
conclusions often because of the inherent problems of retrospective and
uncontrolled study design.
PMID- 17029534
TI - Effects of self-etching primer on shear bond strength of orthodontic brackets at
different debond times.
AB - OBJECTIVE: To evaluate the effect of a self-etching primer on shear bond
strengths (SBS) at the different debond times of 5, 15, 30, and 60 minutes and 24
hours. MATERIALS AND METHODS: Brackets were bonded to human premolars with
different etching protocols. In the control group (conventional method [CM])
teeth were etched with 37% phosphoric acid. In the study group, a self-etching
primer (SEP; Transbond Plus Self Etching Primer; 3M Unitek, Monrovia, Calif) was
applied as recommended by the manufacturer. Brackets were bonded with light-cure
adhesive paste (Transbond XT; 3M Unitek) and light-cured for 20 seconds in both
groups. The shear bond test was performed at the different debond times of 5, 15,
30 and 60 minutes and 24 hours. RESULTS: Lowest SBS was attained with a debond
time of 5 minutes for the CM group (9.51 MPa) and the SEP group (8.97 MPa).
Highest SBS was obtained with a debond time of 24 hours for the CM group (16.82
MPa) and the SEP group (19.11 MPa). Statistically significant differences between
the two groups were not observed for debond times of 5, 15, 30, or 60 minutes.
However, the SBS values obtained at 24 hours were significantly different (P <
.001). CONCLUSIONS: Adequate SBS was obtained with self-etching primer during the
first 60 minutes (5, 15, 30 and 60 minutes) when compared with the conventional
method. It is reliable to load the bracket 5 minutes after bonding using self
etching primer (Transbond Plus) with the light-cure adhesive (Transbond XT).
PMID- 17029535
TI - Maxillary canine--first premolar transposition.
AB - Tooth transpositions present at a relatively low incidence in the world
population and primarily affect maxillary canines and premolars. Treatment of
this disturbance should take into account aspects such as facial pattern, age,
malocclusion, tooth-size discrepancy, stage of eruption, and magnitude of the
transposition. Mechanics for correction should be entirely individualized,
reducing the risks and adverse effects. Practitioners often select simpler
options, indicating extraction of permanent teeth, which is an irreversible
procedure that may bring about damages to the patient. This study presents a case
report and treatment of unilateral transposition of maxillary canine and premolar
with repositioning of affected teeth to their respective normal positions.
PMID- 17029536
TI - Unusual extraction treatment in Class II division 1 using C-orthodontic mini
implants.
AB - This paper describes the treatment of a female patient, aged 23 years and 5
months, with a Class II division 1 malocclusion, who showed severe anterior
protrusion and lower anterior crowding. Specially-designed orthodontic mini
implants were placed bilaterally in the interdental space between both the upper
and the lower posterior teeth. Both lower first molars showed severe apical
lesions. Therefore, the treatment plan consisted of extraction of both upper
first premolars and lower first molars, en masse retraction of the upper six
anterior teeth, lower anterior alignment, and protraction of all the lower
molars. C-implants(R) were used as substitutes for maxillary posterior anchorage
teeth during anterior retraction and as hooks for mandibular molar protraction.
The correct overbite and overjet were obtained by intruding and retracting the
upper six anterior teeth into their proper positions. The dentition was detailed
using conventional orthodontic appliances. The upper C-implants contributed to an
improvement in facial balance, and the lower C-implants made it possible to
protract the lower second and third molars with less effect on the axis of the
lower anterior teeth. The active treatment period was 29 months and the patient's
teeth continued to be stable 11 months after debonding.
PMID- 17029537
TI - Mesial migration effect on root morphology of mandibular third molars.
AB - OBJECTIVE: To test the hypothesis that there is a relationship between forward
mandibular third molar migration and root curvature of the mandibular third
molars. MATERIALS AND METHODS: The study is comprised of 64 patients who had a
history of unilateral mandibular first molar extraction before 16 years of age
with no other missing teeth or prosthetic restorations in the mandible. The
extraction space was fully or partly closed. The mean remaining space was 1.1 +/-
0.41 mm. The root angles for the mesial and distal roots of the mandibular third
molars were measured on the panoramic radiographs by calculating the differences
between the angle formed by the long axis drawn perpendicular to the occlusal
plane of the crown of mandibular third molar and the central line of the lower
one ninth of the root through the root apex. The differences between the
extracted and nonextracted sides for mesial and distal roots were analyzed using
a paired sample t-test. RESULTS: Both mesial and distal roots were approximately
8 degrees more vertical on the extraction sides than on the nonextraction sides.
The differences were statistically significant. CONCLUSION: Mesial tooth
migration of mandibular third molars reduces the amount of root curvature
developing on this tooth.
PMID- 17029538
TI - Chinese norms of McNamara's cephalometric analysis.
AB - OBJECTIVE: To establish cephalometric norms of McNamara's analysis in young
Chinese and compare them to those of a matched young Caucasian sample. MATERIALS
AND METHODS: The material comprised lateral cephalometric radiographs of a random
sample of 200 male and 205 female 12-year-old southern Chinese children, and an
additional sample of 43 male and 43 female 12-year-old British Caucasian children
in Hong Kong. The radiographs were digitized twice with the CASSOS program.
RESULTS: The results showed that there were statistically significant gender
differences for six out of the 11 cephalometric variables in the Chinese, but for
only one variable in the Caucasians. The size of the statistically significant
gender differences varied from -0.3 to 0.4 on SD scores. There were statistically
significant ethnic differences for eight variables in males and seven variables
in females. The size of the observed statistically significant ethnic differences
varied from -1.8 to 1.6 on SD scores. CONCLUSION: The use of specific standards
for Chinese, separate for gender, for McNamara's cephalometric analysis seems to
be justified.
PMID- 17029539
TI - Perceptions of orthognathic surgery patient's change in profile. A five-year
follow-up.
AB - OBJECTIVES: To compare pairs of silhouettes generated from presurgical and 5-year
postsurgical cephalometric radiographs to evaluate whether orthodontists, oral
surgeons, and lay persons perceive changes in profile resulting from orthodontics
and mandibular advancement surgical treatment. MATERIALS AND METHODS: A survey
based method of data collection was used to evaluate 15 pairs of silhouettes.
These silhouettes included 1 control pair and 14 surgically treated pairs
representing mandibular advancements ranging from 0.11 mm to 10.13 mm. Collected
data were analyzed to determine whether changes can be perceived and whether
these changes were esthetically pleasing. RESULTS: The control silhouette pair
was identified by 104 of 127 evaluators. For the 14 surgical treated silhouette
pairs, the vast majority of evaluators (N = 127; 53 orthodontists, 32 oral
surgeons, and 42 lay persons) were able to identify changes in profile and
individual features. At least one group of evaluators was able to perceive
significant (P < .05) improvement in the visual analog scale (VAS) score for all
these silhouette pairs, except for the pair with 10.13 mm of mandibular
advancement. This silhouette pair, which represented the largest mandibular
advancement, was perceived to have a significant (P < .05) worsening in the VAS
score by the lay person group. There were significant differences among the
groups of evaluators. Esthetic improvement in profile was perceived for 13 of 14
surgically treated silhouette pairs. CONCLUSION: In some cases, orthodontists,
oral surgeons, and lay persons perceived changes in profile differently.
PMID- 17029540
TI - Apoptosis of growth plate chondrocytes occurs through a mitochondrial pathway.
AB - OBJECTIVE: To determine the role of mitochondria in chondrocyte apoptosis induced
by inorganic phosphate (Pi). MATERIALS AND METHODS: Chondrocytes isolated from
the growth plates of chick embryo tibia were treated with Pi in serum-free media;
chondrocyte viability, mitochondrial membrane potential, cytochrome c release
from mitochondria, caspase 3 activity, endonuclease activity, and DNA
fragmentation were investigated. RESULTS: Exposure to Pi for 24 hours induced
apoptosis in growth plate chondrocytes through a pathway that involved loss of
mitochondrial function, release of cytochrome c into the cytoplasm, increases in
caspase 3 and endonuclease activities, and fragmentation of DNA. CONCLUSIONS:
This study suggests that mitochondria are important players in Pi-induced
apoptosis.
PMID- 17029541
TI - Friction of conventional and silica-insert ceramic brackets in various bracket
wire combinations.
AB - OBJECTIVE: To compare the level of friction resistance (FR) of conventional and
silica-insert ceramic brackets using various bracket-wire combinations and
angulations. MATERIALS AND METHODS: Four types of ceramic brackets were examined:
(1) polycrystalline alumina bracket (PCA-C), (2) polycrystalline alumina bracket
with a stainless steel (SS) slot (PCA-M), (3) polycrystalline alumina bracket
with a silica layer (PCA-S), and (4) monocrystalline sapphire bracket (MCS). A
conventional SS bracket was used as the control. The static and kinetic FR in
four bracket-wire angulations (0 degrees, 5 degrees, 10 degrees, and 15 degrees)
was examined using SS and beta-titanium (beta-Ti) orthodontic wires, 0.019 x
0.025 inches in size, under elastic ligature in the dry state. RESULTS: The FR
generated by the PCA-S bracket was significantly lower than that generated with
the other ceramic brackets, and was similar to that of the SS bracket. The PCA-S
bracket showed the lowest FR with both the SS and the beta-Ti wires at zero
bracket angulation. The FR to sliding increased rapidly and nonlinearly when the
bracket wire angulation was >5 degrees. The PCS-S bracket showed the lowest FR
from 5 degrees to 15 degrees of angulation. The MCS bracket demonstrated the
highest increase in FR from 0 degrees to 15 degrees of angulation, showing the
highest FR at 15 degrees of angulation. CONCLUSION: PCA-S showed minimal FR among
the ceramic brackets, and was comparable to the conventional SS bracket. The
silica layer and rounded edges of the ceramic slot lowered FR considerably.
PMID- 17029542
TI - Three cements used for orthodontic banding of porcelain molars.
AB - OBJECTIVE: Objectives of this study were to (1) compare the mean shear-peel bond
strength of orthodontic bands luted to porcelain molar denture teeth with glass
ionomer cement (GIC), resin-modified glass ionomer cement (RMGIC), or compomer
cement; (2) assess the amount of cement remaining on the teeth after debanding;
and (3) compare the survival times of the cemented bands subject to mechanical
fatigue. MATERIALS AND METHODS: Sixty banded denture teeth (20 per cement group)
were used to determine shear-peel bond strength, and 30 banded denture teeth (10
per cement group) were used to determine fatigue survival time. Shear-peel bond
strength was determined with a universal testing machine, and groups were
compared by one-way analysis of variance. The amount of cement remaining on the
teeth after band removal was scored, and a chi-square test was used to compare
groups. Fatigue testing was conducted in a ball mill, and a log-rank test was
used to compare differences in survival times. RESULTS: No differences were found
in mean shear-peel bond strength among the three groups. The amount of cement
remaining on the teeth varied between the compomer and GIC groups (P = .01), with
more compomer cement remaining relative to GIC. The mean survival times of bands
cemented with compomer or RMGIC were longer than for bands cemented with GIC (P <
.001). CONCLUSION: The findings show that on porcelain teeth the band cements
have comparable mean shear-peel bond strengths, but that band retention with
RMGIC and compomer cement are superior to GIC when subjected to simulated
mechanical fatigue.
PMID- 17029544
TI - The third-order angle and the maxillary incisor's inclination to the NA line.
AB - OBJECTIVE: To evaluate the relationship between the angular measurement data
(incisor's long axis to NA line) and the third-order angle (TA) according to
Andrews' description. MATERIALS AND METHODS: The materials in the study included
the lateral radiographs and corresponding dental casts of 32 males and 35 females
between 10 and 25 years of age, regardless of their skeletal and dental
relationships. All subjects were white and none had undergone orthodontic
therapy. Using lateral radiographs, upper and lower incisor angulations were
assessed in reference to the NA line. These data were compared with third-order
angles derived from direct dental cast measurements, which were performed using
an incisor inclination recording appliance. RESULTS: The third-order angle
measurements recorded from the dental casts were a mean of 16.2 degrees (SD = 5.3
degrees) smaller than the axial inclination according to the NA line. In this
sample, there was a range of 42.7 degrees for the TA variable (mean = 5.6
degrees, SD = 9.73 degrees) and 47 degrees for the 1NA/deg variable (mean = 21.7
degrees, SD = 8.67 degrees). A highly significant correlation existed (r = 0.84)
between Andrews' angle and the inclination estimated in reference to the NA line.
CONCLUSION: Incisor inclination can be better estimated by recognizing the
relationship between the torque angle and the axial inclination referred to the
NA line. Third-order measurements using dental casts can offer a simple way to
get an objective and rapid vision of the incisor's inclination.
PMID- 17029543
TI - Effect of enamel etching on tensile bond strength of brackets bonded in vivo with
a resin-reinforced glass ionomer cement.
AB - OBJECTIVE: To evaluate the influence of enamel etching on tensile bond strength
of orthodontic brackets bonded with resin-reinforced glass ionomer cement.
MATERIALS AND METHODS: The sample group consisted of 15 patients who had
indications for extraction of four premolars for orthodontic reasons, equally
divided into two different groups according to bracket and enamel preparation.
Brackets were bonded in vivo, by the same operator, using a split mouth random
technique: Group 1 (control), phosphoric acid + Fuji Ortho LC; Group 2, Fuji
Ortho LC without acid conditioning. The teeth were extracted after 4 weeks using
elevators. An Instron Universal Testing Machine was used to apply a tensile force
directly to the enamel-bracket interface at a speed of 0.5 mm/min. The groups
were compared using a Mann-Whitney U-test and Weibull analysis. RESULTS: Mean
results and standard deviations (in MPa) for the groups were: Group 1, 6.26
(3.21), Group 2, 6.52 (2.73). No significant difference was observed in the bond
strengths of the two groups evaluated (P = .599). CONCLUSIONS: Fuji Ortho LC
showed adequate shear bond strength and may be suitable for clinical use.
PMID- 17029545
TI - Congenital missing permanent teeth in Korean unilateral cleft lip and alveolus
and unilateral cleft lip and palate patients.
AB - OBJECTIVE: To investigate the differences in the congenital missing teeth pattern
in terms of tooth type (permanent maxillary lateral incisor [MLI] and maxillary
second premolar [MSP]) and sidedness (cleft vs noncleft) between boys and girls
in Korean unilateral cleft lip and alveolus (UCLA) and unilateral cleft lip and
palate (UCLP) patients. MATERIALS AND METHODS: This study used the charts,
models, radiographs, and intraoral photographs of 90 UCLA patients and 204 UCLP
patients (ages 6 to 13 years). Binomial test, chi-square test, Fisher exact test,
maximum likelihood analysis of variance, and the odds ratio were performed.
RESULTS: According to the relationship between the congenital missing teeth
pattern and the cleft type, the UCLP patients had 2.98 times more missing MLIs
and 1.80 times more missing MSPs than did the UCLA patients. The MLI was
congenitally missing more in boys than in girls, but the MSP showed the opposite
tendency. Boys had a higher frequency of congenital missing MLIs and MSPs on the
cleft side than did girls. However, on the noncleft side and both sides, girls
had a higher frequency of congenital missing MLIs and MSPs than did boys. Results
showed a gender-dominant pattern of congenital missing MLIs and MSPs. CONCLUSION:
These results suggest that gender and cleft type might affect the congenital
missing teeth pattern in terms of tooth type and sidedness.
PMID- 17029546
TI - An evaluation of buccal shield treatment. A clinical and cephalometric study.
AB - OBJECTIVE: To evaluate the short-term effects of the buccal shield modification
of the lip-bumper design and on various mandibular dental arch parameters and to
determine whether the changes in arch widths are due to the tipping or bodily
movements of the teeth involved. MATERIALS AND METHODS: This study included 45
consecutively treated patients (29 girls and 16 boys) from a private orthodontic
practice. Student's and paired t-tests were used to test the null hypothesis of
no change over time for the various measurements. Linear regression analyses were
used to determine whether treatment time was a significant predictor of arch
width expansion. Significance for all statistical tests was predetermined at P <
or = .05. RESULTS: Student's t-test results indicated the presence of a
significant (P < .0001) increase in all the arch parameters measured. The
greatest mean expansion was observed at the first (5.0 +/- 2.2 mm) and second
(3.4 +/- 2.2 mm) premolar width measurements. The changes in arch width
parameters were significantly (P < .0001) greater than the normal age-related
changes in the corresponding parameters. There was no significant difference
between arch width expansion of the occlusal vs gingival levels, indicating a
bodily and not tipping movement. Only 30% of the lower incisors demonstrated an
increase in their proclination beyond normal values. CONCLUSION: When using the
buccal shield appliance, the mandibular arch width parameters can be expanded in
the mixed dentition with bodily movement of teeth. The expanded arch width
dimensions are greater than what would be expected as a result of normal growth.
PMID- 17029547
TI - Dentoskeletal effects and "effective" temporomandibular joint, maxilla and chin
changes in good and bad responders to van Beek activator treatment.
AB - OBJECTIVE: To assess possible differences in dentoskeletal effects and
"effective" temporomandibular joint, maxilla, and chin changes between good and
bad responders to van Beek activator treatment. MATERIALS AND METHODS: The
subject material consisted of 20 consecutive normodivergent male Class II
division 1 patients treated with a van Beek activator. Because of insufficient
cooperation, four patients were excluded. Lateral head films were taken 6 months
before treatment, at start of treatment, and after 12 months of treatment. The
patients were placed into a good responder group (successful, n = 8) and a bad
responder group (unsuccessful, n = 8). An overjet reduction > or =4 mm was
considered successful. RESULTS: During the van Beek treatment period, the good
responders showed a significantly larger improvement in overjet and molar
relationship than did the bad responders. The good responders exhibited a
significant posterior development of condylion, less anterior mandibular
autorotation, retrusion of upper incisors, protrusion of lower incisors,
distalization of maxillary molars, and a mesial movement of mandibular molars. No
significant dental movements were seen in the bad responders. CONCLUSIONS:
Although van Beek activator treatment affected the direction of condylar growth,
as well as the direction of maxilla and chin changes, it can be concluded that
skeletal changes did not contribute to the Class II correction. Instead, overjet
reduction during van Beek activator treatment was found to be due to a favorable
dental reaction.
PMID- 17029548
TI - Etching enamel for orthodontics with an erbium, chromium:yttrium-scandium-gallium
garnet laser system.
AB - OBJECTIVE: To test the shear bond strength, surface characteristics, and fracture
mode of brackets that are bonded to enamel etched with an erbium,
chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser operated at different
power outputs: 0.5 W, 1 W, and 2 W. MATERIALS AND METHODS: Human premolars that
had been extracted for orthodontic purposes were used. Enamel was etched with an
Er,Cr:YSGG laser system operated at one of three power outputs or with
orthophosphoric acid. RESULTS: The shear bond strength associated with the 0.5-W
laser irradiation was significantly less than the strengths obtained with the
other irradiations. Both the 1-W and 2-W laser irradiations were capable of
etching enamel in the same manner. This finding was confirmed by scanning
electron microscopy examination. The evaluation of adhesive-remnant-index scores
demonstrated no statistically significant difference in bond failure site among
the groups, except for the 0.5-W laser-etched group. Generally, more adhesive was
left on the enamel surface with laser irradiation than with acid etching.
CONCLUSION: The mean shear bond strength and enamel surface etching obtained with
an Er,Cr: YSGG laser (operated at 1 W or 2 W for 15 seconds) is comparable to
that obtained with acid etching.
PMID- 17029549
TI - Tumor necrosis factor-alpha levels during two different canine distalization
techniques.
AB - OBJECTIVES: To compare levels of tumor necrosis factor (TNF)-alpha while applying
continuous and heavy interrupted forces. MATERIALS AND METHODS: A hybrid
retractor was used in the first group. In the second group, rapid canine
distalization through periodontal distraction was performed. Gingival crevicular
fluid samples were collected from the distal sides of the canine teeth before
attaching the appliances and at 1 hour, 24 hours, and 1 week after the force was
applied. RESULTS: In the hybrid reactor group, concentration of TNF-alpha
decreased at 1 week according to 24-hour measurements. In the rapid canine
distalization group, it severely increased at 1 hour. In the evaluation of
between-group differences, significantly higher values were determined in the
rapid canine distalization group at 1 hour and 1 week. CONCLUSIONS: Heavy
interrupted force induces a rapid release of TNF-alpha, and the tissue response
continues for a longer time period. To avoid the harmful effects of heavy
interrupted force, there might be feedback mechanisms that prevent the mediators
from increasing excessively.
PMID- 17029550
TI - Trunk inclination, pelvic tilt and pelvic rotation in relation to the
craniofacial morphology in adults.
AB - OBJECTIVE: To relate the differences in the posture of patients with different
craniofacial morphologies. SUBJECTS AND METHODS: Fifty-three adult patients with
Class II and III malformations were examined by cephalometric analysis and
rasterstereography. The facial depth, maxillary position, mandibular plane angle,
inner gonial angle, facial axis, and lower facial height were evaluated and
classified into a basal distal-mesial group and a horizontal-vertical group by
means of threshold parameters. Analyzing the results of the rasterstereography,
the spine's lateral perpendicular deviation, the pelvic tilt, and the pelvic
rotation were calculated by means of mathematical algorithms on the basis of the
three-dimensional spine profile. To determine the statistically significant
correlations between the studied parameters, the t-test was applied in groups
with a normal distribution, and the Mann-Whitney U-test was used in the cases of
abnormally distributed variables (significance level P < .05). RESULTS:
Statistically significant differences (P < .05) in pelvic torsion were documented
with respect to the facial axis and facial depth. Moreover, the differences (P <
.05) between patients with a skeletal horizontal-vertical facial axis and
patients with a basal distal-mesial position for the facial depth could be
determined for the pelvic torsion. CONCLUSIONS: As a clinical consequence of the
results, an extension of the interdisciplinary concepts within the sense of an
orthopedic examination can be considered for patients undergoing a combined
orthodontic-operative therapy.
PMID- 17029551
TI - Effects of cervical headgear on overbite against the background of existing
growth patterns. A retrospective analysis of study casts.
AB - OBJECTIVE: To test the questions "Does cervical headgear treatment necessarily
lead to a reduction of overbite?" and "Are there differences in treatment results
due to different growth patterns or the initial overbite?" MATERIALS AND METHODS:
Initial and intermediary casts of 247 patients who had been treated exclusively
with headgear were analyzed for changes in the occlusal relationship of the first
molars and overbite. Orthodontic treatment consisted of the application of
cervical headgear with nonangulated external arms applied at a force of 3.5-4.0
N. Only patients showing dental changes of occlusal relationship > or = 4 mm
during at least a 6-month treatment duration were selected. Growth patterns were
identified by the y-axis values measured on lateral cephalograms obtained at
study entry. Six groups were formed on the basis of these growth patterns.
RESULTS: Headgear treatment induced bite deepening in patients with vertical
growth patterns and bite opening in patients with horizontal growth patterns.
Further subdivision based on initial overbite revealed bite deepening in patients
with small initial overbite and bite opening in patients with large initial
overbite. These differences were statistically significant (P < .05). Only minor
changes were observed in patients with an initial overbite of 3-4 mm.
CONCLUSIONS: Overbite reductions were not dependent on the growth pattern.
Orthodontists should expect bite opening in deep-bite situations and bite
deepening in open-bite situations. However, initial overbite situations of 3-4 mm
should not be expected to change in a significant way.
PMID- 17029552
TI - Effects of interferon-gamma on bone remodeling during experimental tooth
movement.
AB - OBJECTIVE: To determine the effects of interferon-gamma (IFN-gamma) on bone
remodeling during orthodontic tooth movement. MATERIALS AND METHODS: Thirty adult
male Sprague Dawley rats were randomly categorized into five groups. IFN-gamma
was administered in three different doses (0.01, 0.02, and 0.05 microg/20 microL)
and the remaining two groups served as control. Mandibular first molars were
moved mesially by means of Ni-Ti closed coil springs in all groups. The results
were evaluated histomorphometrically, and parameters of trabecular bone volume
(BV/TV), trabecular bone number (Tr.N), and trabecular separation (Tr.Sep) were
observed at the interradicular bone area of the mandibular first molars. RESULTS:
Increases in BV/TV and Tr.N and decreases in Tr.Sep revealed the antiosteoclastic
activity of IFN-gamma. CONCLUSION: IFN-gamma administration may be useful
clinically for anchorage control.
PMID- 17029553
TI - A fused maxillary central incisor with dens evaginatus as a talon cusp.
AB - This report presents a rare case of concurrence of dens evaginatus and dental
fusion affecting the maxillary right upper central incisor of a 9-year-old male
patient. An association of dens evaginatus and dental fusion within the same
tooth is rare. In this case, an orthopantomogram, a lateral cephalogram,
intraoral radiographs, and a magnetic resonance tomogram were made to obtain a
proper diagnosis and to confirm the exact path of the root canals. Because of a
forced bite, an orthodontic treatment involving cusp reduction was initiated.
During the cusp reduction, no traumatic intraoperative exposure of pulp tissue
occurred, and no endodontic or surgical treatment procedures were necessary.
After a multibracket treatment, a harmonious integration of the tooth in the
upper dental arch was achieved.
PMID- 17029554
TI - Short-term effect of mastic gum on salivary concentrations of cariogenic bacteria
in orthodontic patients.
AB - OBJECTIVE: To determine antibacterial activity of chewing mastic gum against the
salivary levels of Streptococcus mutans, the total number of viable bacteria, and
lactobacilli in patients undergoing therapy with fixed orthodontic appliances.
MATERIALS AND METHODS: In this study, the levels of S mutans, lactobacilli, and
total cultivated bacteria were measured before and after chewing mastic gum. The
antibacterial effects of chewing mastic gum against these microorganisms in
saliva were compared with a placebo gum. The counts for orthodontically treated
patients were evaluated before chewing gum; just after chewing gum; and after 45,
75, 105, and 135 minutes. Saliva samples taken from the patients were inoculated
onto trypticase-yeast-cystine-bacitracin agar for mutans streptococci and onto
Rogosa agar for lactobacilli. The agar plates were incubated for 48 hours
anaerobically at 37 degrees C. The total number of viable bacteria was then
counted. RESULTS: Just after chewing the mastic gum for 15 minutes, a significant
decrease of total bacteria and S mutans was observed (P < .001). The reduction in
lactobacilli was not significant at later first stage (P > .05). However, at the
end of 135 minutes, there were significantly fewer S mutans (P < .001), total
viable bacteria (P < .001), and lactobacilli (P < .001) in the oral cavity after
chewing mastic gum than after chewing paraffin (P < .001). The results show that
chewing mastic gum decreased the total viable bacteria, S mutans, and
lactobacilli in saliva in orthodontically treated patients with fixed appliances.
CONCLUSION: Chewing mastic gum might be useful in preventing caries lesions.
PMID- 17029555
TI - Mandibular first molar relation to variable lower face skeletal components.
AB - OBJECTIVE: To evaluate the position of the mandibular first permanent molar in
the mandible relative to several factors. MATERIALS AND METHODS: A total of 185
untreated Class I and Class II patients were randomly selected from a sample of
350 patients from a single office. The palatal and mandibular planes were related
to Frankfort horizontal to create the interjaw or "B" angle. Age and the mesial
contact of the mandibular first molars were used. The landmarks were projected at
right angles to the Frankfort horizontal for effective mandibular dimension
lengths. Actual-length dimensions were projected at right angles to the
mandibular plane. Pearson product moment correlation coefficients were computed
to evaluate the effect of age, cranial length, and mandibular contribution to the
molar's sagittal position in the mandible. Significance was reported only when P
< .05 to determine a 95% confidence level. RESULTS: Statistically significant
positive correlations indicated that the mandibular molar is located more forward
with increasing age, longer mandibular body length, and increasing posterior
facial height. In contrast, significant negative correlations to the interjaw,
mandibular plane, ramal inclination angles, and the linear ramal contribution
corresponded to a more posterior position of the molar with increasing angles.
CONCLUSIONS: The mandibular first permanent molar is located more anteriorly with
an older patient, a longer mandibular body, greater posterior facial height, and
an acute interjaw angle. In contrast, an increase in the forward tip of the ramus
places the molar in a more posterior location.
PMID- 17029556
TI - Simulating properties of in vitro epithelial cell morphogenesis.
AB - How do individual epithelial cells (ECs) organize into multicellular structures?
ECs are studied in vitro to help answer that question. Characteristic growth
features include stable cyst formation in embedded culture, inverted cyst
formation in suspension culture, and lumen formation in overlay culture.
Formation of these characteristic structures is believed to be a consequence of
an intrinsic program of differentiation and de-differentiation. To help discover
how such a program may function, we developed an in silico analogue in which
space, events, and time are discretized. Software agents and objects represent
cells and components of the environment. "Cells" act independently. The "program"
governing their behavior is embedded within each in the form of axioms and an
inflexible decisional process. Relationships between the axioms and recognized
cell functions are specified. Interactions between "cells" and environment
components during simulation give rise to a complex in silico phenotype
characterized by context-dependent structures that mimic counterparts observed in
four different in vitro culture conditions: a targeted set of in vitro phenotypic
attributes was matched by in silico attributes. However, for a particular growth
condition, the analogue failed to exhibit behaviors characteristic of
functionally polarized ECs. We solved this problem by following an iterative
refinement method that improved the first analogue and led to a second: it
exhibited characteristic differentiation and growth properties in all simulated
growth conditions. It is the first model to simultaneously provide a
representation of nonpolarized and structurally polarized cell types, and a
mechanism for their interconversion. The second analogue also uses an inflexible
axiomatic program. When specific axioms are relaxed, growths strikingly
characteristic of cancerous and precancerous lesions are observed. In one case,
the simulated cause is aberrant matrix production. Analogue design facilitates
gaining deeper insight into such phenomena by making it easy to replace low
resolution components with increasingly detailed and realistic components.
PMID- 17029557
TI - Natural biocombinatorics in the polyketide synthase genes of the actinobacterium
Streptomyces avermitilis.
AB - Modular polyketide synthases (PKSs) of bacteria provide an enormous reservoir of
natural chemical diversity. Studying natural biocombinatorics may aid in the
development of concepts for experimental design of genes for the biosynthesis of
new bioactive compounds. Here we address the question of how the modularity of
biosynthetic enzymes and the prevalence of multiple gene clusters in Streptomyces
drive the evolution of metabolic diversity. The phylogeny of ketosynthase (KS)
domains of Streptomyces PKSs revealed that the majority of modules involved in
the biosynthesis of a single compound evolved by duplication of a single ancestor
module. Using Streptomyces avermitilis as a model organism, we have reconstructed
the evolutionary relationships of different domain types. This analysis suggests
that 65% of the modules were altered by recombinational replacements that
occurred within and between biosynthetic gene clusters. The natural reprogramming
of the biosynthetic pathways was unambiguously confined to domains that account
for the structural diversity of the polyketide products and never observed for
the KS domains. We provide examples for natural acyltransferase (AT),
ketoreductase (KR), and dehydratase (DH)-KR domain replacements. Potential sites
of homologous recombination could be identified in interdomain regions and within
domains. Our results indicate that homologous recombination facilitated by the
modularity of PKS architecture is the most important mechanism underlying
polyketide diversity in bacteria.
PMID- 17029559
TI - Application of genome-wide single nucleotide polymorphism typing: simple
association and beyond.
AB - The International HapMap Project and the arrival of technologies that type more
than 100,000 SNPs in a single experiment have made genome-wide single nucleotide
polymorphism (GW-SNP) assay a realistic endeavor. This has sparked considerable
debate regarding the promise of GW-SNP typing to identify genetic association in
disease. As has already been shown, this approach has the potential to localize
common genetic variation underlying disease risk. The data provided from this
technology also lends itself to several other lines of investigation;
autozygosity mapping in consanguineous families and outbred populations, direct
detection of structural variation, admixture analysis, and other population
genetic approaches. In this review we will discuss the potential uses and
practical application of GW-SNP typing including those above and beyond simple
association testing.
PMID- 17029558
TI - Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media.
AB - Otitis media (OM), inflammation of the middle ear, remains the most common cause
of hearing impairment in children. It is also the most common cause of surgery in
children in the developed world. There is evidence from studies of the human
population and mouse models that there is a significant genetic component
predisposing to OM, yet nothing is known about the underlying genetic pathways
involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse
mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This
develops from acute OM that arises spontaneously in the postnatal period, with
the age of onset and early severity dependent on the microbiological status of
the mice and their air quality. We have identified the causal mutation, a
missense change in the C-terminal zinc finger region of the transcription factor
Evi1. This protein is expressed in middle ear basal epithelial cells,
fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when
inflammatory changes are underway. The identification and characterization of the
Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates
a new pathway in genetic predisposition to OM.
PMID- 17029560
TI - Heterogeneous genomic molecular clocks in primates.
AB - Using data from primates, we show that molecular clocks in sites that have been
part of a CpG dinucleotide in recent past (CpG sites) and non-CpG sites are of
markedly different nature, reflecting differences in their molecular origins.
Notably, single nucleotide substitutions at non-CpG sites show clear generation
time dependency, indicating that most of these substitutions occur by errors
during DNA replication. On the other hand, substitutions at CpG sites occur
relatively constantly over time, as expected from their primary origin due to
methylation. Therefore, molecular clocks are heterogeneous even within a genome.
Furthermore, we propose that varying frequencies of CpG dinucleotides in
different genomic regions may have contributed significantly to conflicting
earlier results on rate constancy of mammalian molecular clock. Our conclusion
that different regions of genomes follow different molecular clocks should be
considered when inferring divergence times using molecular data and in
phylogenetic analysis.
PMID- 17029561
TI - Transposition of reversed Ac element ends generates novel chimeric genes in
maize.
AB - The maize Activator/Dissociation (Ac/Ds) elements are members of the hAT (hobo,
Ac, and Tam3) superfamily of type II (DNA) transposons that transpose through a
"cut-and-paste" mechanism. Previously, we reported that a pair of Ac ends in
reversed orientation is capable of undergoing alternative transposition reactions
that can generate large-scale chromosomal rearrangements, including deletions and
inversions. We show here that rearrangements induced by reversed Ac ends
transposition can join the coding and regulatory sequences of two linked
paralogous genes to generate a series of chimeric genes, some of which are
functional. To our knowledge, this is the first report demonstrating that
alternative transposition reactions can recombine gene segments, leading to the
creation of new genes.
PMID- 17029563
TI - Tryptophan 171 in Pharaonis phoborhodopsin (sensory rhodopsin II) interacts with
the chromophore retinal and its substitution with alanine or threonine slowed
down the decay of M- and O-intermediate.
AB - Pharaonis phoborhodopsin (ppR), also called pharaonis sensory rhodopsin II,
NpSRII, is a photoreceptor for the photophobic response of Natronomonas
pharaonis. Tryptophan 182 (W182) of bacteriorhodopsin (bR) is near the
chromophore retinal and has been suggested to interact with retinal during the
photoreaction and also to be involved in the hydrogen-bonding network around the
retinal. W182 of bR is conserved in ppR as tryptophan 171 (W171). To elucidate
whether W171 of ppR interacts with retinal during the photoreaction and/or is
involved in the hydrogen-bonding network as in bR, we formed W171-substituted
mutants of ppR, W171A and W171T. Our low-temperature spectroscopic study has
revealed that the substitution of W171 to Ala or Thr resulted in the
stabilization of M- and O-intermediates. The stability of M and absorption
spectral changes during the M-decay were different depending on the substituted
residue. These findings suggest that W171 in ppR interacts with retinal and the
degree of the interaction depends on the substituted residues, which might be
rate determining in the M-decay. In addition, the involvement of W171 in the
hydrogen-bonding network is suggested by the O-decay. We also found that glycerol
slowed the decay of M and not of O.
PMID- 17029562
TI - Heat-shock promoters: targets for evolution by P transposable elements in
Drosophila.
AB - Transposable elements are potent agents of genomic change during evolution, but
require access to chromatin for insertion-and not all genes provide equivalent
access. To test whether the regulatory features of heat-shock genes render their
proximal promoters especially susceptible to the insertion of transposable
elements in nature, we conducted an unbiased screen of the proximal promoters of
18 heat-shock genes in 48 natural populations of Drosophila. More than 200
distinctive transposable elements had inserted into these promoters; greater than
96% are P elements. By contrast, few or no P element insertions segregate in
natural populations in a "negative control" set of proximal promoters lacking the
distinctive regulatory features of heat-shock genes. P element transpositions
into these same genes during laboratory mutagenesis recapitulate these findings.
The natural P element insertions cluster in specific sites in the promoters, with
up to eight populations exhibiting P element insertions at the same position;
laboratory insertions are into similar sites. By contrast, a "positive control"
set of promoters resembling heat-shock promoters in regulatory features harbors
few P element insertions in nature, but many insertions after experimental
transposition in the laboratory. We conclude that the distinctive regulatory
features that typify heat-shock genes (in Drosophila) are especially prone to
mutagenesis via P elements in nature. Thus in nature, P elements create
significant and distinctive variation in heat-shock genes, upon which
evolutionary processes may act.
PMID- 17029564
TI - Causal cognition in human and nonhuman animals: a comparative, critical review.
AB - In this article, we review some of the most provocative experimental results to
have emerged from comparative labs in the past few years, starting with research
focusing on contingency learning and finishing with experiments exploring
nonhuman animals' understanding of causal-logical relations. Although the
theoretical explanation for these results is often inchoate, a clear pattern
nevertheless emerges. The comparative evidence does not fit comfortably into
either the traditional associationist or inferential alternatives that have
dominated comparative debate for many decades now. Indeed, the similarities and
differences between human and nonhuman causal cognition seem to be much more
multifarious than these dichotomous alternatives allow.
PMID- 17029566
TI - Mitochondrial oxidative stress: implications for cell death.
AB - In addition to the established role of the mitochondria in energy metabolism,
regulation of cell death has emerged as a second major function of these
organelles. This seems to be intimately linked to their generation of reactive
oxygen species (ROS), which have been implicated in mtDNA mutations, aging, and
cell death. Mitochondrial regulation of apoptosis occurs by mechanisms, which
have been conserved through evolution. Thus, many lethal agents target the
mitochondria and cause release of cytochrome c and other pro-apoptotic proteins
into the cytoplasm. Cytochrome c release is initiated by the dissociation of the
hemoprotein from its binding to the inner mitochondrial membrane. Oxidation of
cardiolipin reduces cytochrome c binding and increases the level of soluble
cytochrome c in the intermembrane space. Subsequent release of the hemoprotein
occurs by pore formation mediated by pro-apoptotic Bcl-2 family proteins, or by
Ca(2+) and ROS-triggered mitochondrial permeability transition, although the
latter pathway might be more closely associated with necrosis. Taken together,
these findings have placed the mitochondria in the focus of current cell death
research.
PMID- 17029565
TI - Research on attention networks as a model for the integration of psychological
science.
AB - As Titchener pointed out more than one hundred years ago, attention is at the
center of the psychological enterprise. Attention research investigates how
voluntary control and subjective experience arise from and regulate our behavior.
In recent years, attention has been one of the fastest growing of all fields
within cognitive psychology and cognitive neuroscience. This review examines
attention as characterized by linking common neural networks with individual
differences in their efficient utilization. The development of attentional
networks is partly specified by genes, but is also open to specific experiences
through the actions of caregivers and the culture. We believe that the connection
between neural networks, genes, and socialization provides a common approach to
all aspects of human cognition and emotion. Pursuit of this approach can provide
a basis for psychology that unifies social, cultural, differential, experimental,
and physiological areas, and allows normal development to serve as a baseline for
understanding various forms of pathology. D.O. Hebb proposed this approach 50
years ago in his volume Organization of Behavior and continued with introductory
textbooks that dealt with all of the topics of psychology in a common framework.
Use of a common network approach to psychological science may allow a foundation
for predicting and understanding human behavior in its varied forms.
PMID- 17029567
TI - Pharmacogenomic and structural analysis of constitutive g protein-coupled
receptor activity.
AB - G protein-coupled receptors (GPCRs) respond to a chemically diverse plethora of
signal transduction molecules. The notion that GPCRs also signal without an
external chemical trigger, i.e., in a constitutive or spontaneous manner,
resulted in a paradigm shift in the field of GPCR pharmacology. The discovery of
constitutive GPCR activity and the fact that GPCR binding and signaling can be
strongly affected by a single point mutation drew attention to the evolving area
of GPCR pharmacogenomics. For a variety of GPCRs, point mutations have been
convincingly linked to human disease. Mutations within conserved motifs, known to
be involved in GPCR activation, might explain the properties of some naturally
occurring, constitutively active GPCR variants linked to disease. In this review,
we provide a brief historical introduction to the concept of constitutive
receptor activity and the pharmacogenomic and structural aspects of constitutive
receptor activity.
PMID- 17029568
TI - The impact of glycosylation on the biological function and structure of human
immunoglobulins.
AB - Immunoglobulins are the major secretory products of the adaptive immune system.
Each is characterized by a distinctive set of glycoforms that reflects the wide
variation in the number, type, and location of their oligosaccharides. In a given
physiological state, glycoform populations are reproducible; therefore, disease
associated alterations provide diagnostic biomarkers (e.g., for rheumatoid
arthritis) and contribute to disease pathogenesis. The oligosaccharides provide
important recognition epitopes that engage with lectins, endowing the
immunoglobulins with an expanded functional repertoire. The sugars play specific
structural roles, maintaining and modulating effector functions that are
physiologically relevant and can be manipulated to optimize the properties of
therapeutic antibodies. New molecular models of all the immunoglobulins are
included to provide a basis for informed and critical discussion. The models were
constructed by combining glycan sequencing data with oligosaccharide linkage and
dynamics information from the Glycobiology Institute experimental database and
protein structural data from "The Protein Data Bank."
PMID- 17029569
TI - Abstracts of the American Association for Cancer Education 40th Annual Meeting.
October 12-14, 2006. San Diego, California, USA.
PMID- 17029581
TI - Regulation of commissural axon pathfinding by slit and its Robo receptors.
AB - Commissural axons grow along complex pathways toward, across, and beyond the
midline of the central nervous system. Taking commissural axons in the vertebrate
spinal cord and the Drosophila ventral nerve cord as examples, we examine how
commissural axon pathfinding is regulated by the Slit family of guidance cues and
their Robo family receptors. We extract several principles that seem likely to
apply to other axons and other contexts, such as the reiterative use of the same
guidance molecules in distinct pathfinding decisions, the transcriptional
specification of a pathway, the posttranscriptional regulation of growth along
the pathway, and the possible role of feedback mechanisms to ensure the fidelity
of pathfinding choices. Such mechanisms may help explain how a relatively small
number of guidance molecules can generate complex and stereotyped wiring
patterns. We also highlight the many gaps in our understanding of commissural
axon pathfinding and question some widely accepted views. We hope that this
review encourages further efforts to tackle these questions, in the expectation
that this system will continue to reveal the general principles of axon
pathfinding.
PMID- 17029582
TI - Axonal wiring in the mouse olfactory system.
AB - The main olfactory epithelium of the mouse is a mosaic of 2000 populations of
olfactory sensory neurons (OSNs). Each population expresses one allele of one of
the 1000 intact odorant receptor (OR) genes. An OSN projects a single unbranched
axon to a single glomerulus, from an array of 1600-1800 glomeruli in the main
olfactory bulb. Within a glomerulus the OSN axon synapses with the dendrites of
second-order neurons and interneurons. Axons of OSNs that express the same OR
project to the same glomeruli-typically one glomerulus per half-bulb and thus
four glomeruli per mouse. These glomeruli are located at characteristic positions
within the glomerular layer of the bulb. ORs determine both the odorant response
profile of the OSN and the projection of its axon to a specific glomerulus. I
focus on genetic approaches to the axonal wiring problem, particularly on how ORs
may function in axonal wiring.
PMID- 17029588
TI - Phagocytosis by Trichomonas vaginalis: new insights.
AB - BACKGROUND INFORMATION: The parasitic protozoan Trichomonas vaginalis is the
causative agent of trichomoniasis, a sexually transmitted disease. The phagocytic
activity of this parasite has not been completely elucidated. In order to better
understand the mechanisms of trichomonal phagocytosis, we have studied the in
vitro capacity of T. vaginalis to phagocytose and degrade Saccharomyces
cerevisiae cells. RESULTS AND CONCLUSIONS: To analyse the phagocytic ability and
capacity, two isolates of T. vaginalis presenting different virulence grades were
used. Complementary techniques, such as fluorescence microscopy, computer-based
fluorescence analysis, scanning and transmission electron microscopy and the use
of drugs that interfere with the actin microfilaments, were used in order to
follow the behaviour of the actin cytoskeleton during phagocytosis of yeast cells
by T. vaginalis. It was concluded that: (1) T. vaginalis changes its shape
rapidly and engulfs the yeast cells, which are almost as large as the parasite;
(2) long-term and fresh cultures are able to phagocytose, although the low
virulence strain JT demonstrated a lower activity when compared with the highly
virulent T016 isolate; (3) the T016 strain exhibited an amoeboid morphology
during the internalization of yeast cells in contrast with the JT strain; (4)
attachment of yeast cells to the parasite occurs via the whole cell surface,
including both anterior and recurrent flagella; (5) two forms of phagocytosis
were observed: a 'sinking' process without any apparent participation of plasma
membrane extensions and the classical phagocytosis where pseudopodia are extended
toward the target cell; (6) the internalized S. cerevisiae are digested in
lysosomes; (7) competitor sugars D-mannose or L-fucose inhibit the phagocytosis,
and inhibition was 1.67 times higher in long-term cultured JT than that of the
parasites from fresh isolate T016; (8) a thick layer of actin microfilaments was
present underlying the plasma membrane, and especially in the pseudopodia and
around the phagocytosed particles; (9) a dramatic change in the distribution
pattern of fibrillar actin occurred during phagocytosis; (10) cytochalasin D
depressed the phagocytosis; (11) a non-specific recognition and phagocytosis of
yeast cells by T. vaginalis is mediated by a mannose receptor present on the
parasite surface; (12) the phagocytic process may occur simultaneously during
mitosis of the parasite.
PMID- 17029589
TI - Modulation of drug-stimulated ATPase activity of human MDR1/P-glycoprotein by
cholesterol.
AB - MDR1 (multidrug resistance 1)/P-glycoprotein is an ATP-driven transporter which
excretes a wide variety of structurally unrelated hydrophobic compounds from
cells. It is suggested that drugs bind to MDR1 directly from the lipid bilayer
and that cholesterol in the bilayer also interacts with MDR1. However, the
effects of cholesterol on drug-MDR1 interactions are still unclear. To examine
these effects, human MDR1 was expressed in insect cells and purified. The
purified MDR1 protein was reconstituted in proteoliposomes containing various
concentrations of cholesterol and enzymatic parameters of drug-stimulated ATPase
were compared. Cholesterol directly binds to purified MDR1 in a detergent soluble
form and the effects of cholesterol on drug-stimulated ATPase activity differ
from one drug to another. The effects of cholesterol on K(m) values of drug
stimulated ATPase activity were strongly correlated with the molecular mass of
that drug. Cholesterol increases the binding affinity of small drugs (molecular
mass <500 Da), but does not affect that of drugs with a molecular mass of between
800 and 900 Da, and suppresses that of valinomycin (molecular mass >1000 Da).
V(max) values for rhodamine B and paclitaxel are also increased by cholesterol,
suggesting that cholesterol affects turnover as well as drug binding. Paclitaxel
stimulated ATPase activity of MDR1 is enhanced in the presence of stigmasterol,
sitosterol and campesterol, as well as cholesterol, but not ergosterol. These
results suggest that the drug-binding site of MDR1 may best fit drugs with a
molecular mass of between 800 and 900 Da, and that cholesterol may support the
recognition of smaller drugs by adjusting the drug-binding site and play an
important role in the function of MDR1.
PMID- 17029590
TI - Polyadenylation proteins CstF-64 and tauCstF-64 exhibit differential binding
affinities for RNA polymers.
AB - CstF-64 (cleavage stimulation factor-64), a major regulatory protein of
polyadenylation, is absent during male meiosis. Therefore a paralogous variant,
tauCstF-64 is expressed in male germ cells to maintain normal spermatogenesis.
Based on sequence differences between tauCstF-64 and CstF-64, and on the high
incidence of alternative polyadenylation in testes, we hypothesized that the RBDs
(RNA-binding domains) of tauCstF-64 and CstF-64 have different affinities for RNA
elements. We quantified K(d) values of CstF-64 and tauCstF-64 RBDs for various
ribopolymers using an RNA cross-linking assay. The two RBDs had similar
affinities for poly(G)18, poly(A)18 or poly(C)18, with affinity for poly(C)18
being the lowest. However, CstF-64 had a higher affinity for poly(U)18 than
tauCstF-64, whereas it had a lower affinity for poly(GU)9. Changing Pro-41 to a
serine residue in the CstF-64 RBD did not affect its affinity for poly(U)18, but
changes in amino acids downstream of the C-terminal alpha-helical region
decreased affinity towards poly(U)18. Thus we show that the two CstF-64
paralogues differ in their affinities for specific RNA sequences, and that the
region C-terminal to the RBD is mportant in RNA sequence recognition. This
supports the hypothesis that tauCstF-64 promotes germ-cell-specific patterns of
polyadenylation by binding to different downstream sequence elements.
PMID- 17029592
TI - Cyclin-dependent kinase 5 in synaptic plasticity, learning and memory.
AB - Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase with a multitude of
functions. Although Cdk5 is widely expressed, it has been studied most
extensively in neurons. Since its initial characterization, the fundamental
contribution of Cdk5 to an impressive range of neuronal processes has become
clear. These phenomena include neural development, dopaminergic function and
neurodegeneration. Data from different fields have recently converged to provide
evidence for the participation of Cdk5 in synaptic plasticity, learning and
memory. In this review, we consider recent data implicating Cdk5 in molecular and
cellular mechanisms underlying synaptic plasticity. We relate these findings to
its emerging role in learning and memory. Particular attention is paid to the
activation of Cdk5 by p25, which enhances hippocampal synaptic plasticity and
memory, and suggests formation of p25 as a physiological process regulating
synaptic plasticity and memory.
PMID- 17029591
TI - Towards abolition of immunogenic structures in insect cells: characterization of
a honey-bee (Apis mellifera) multi-gene family reveals both an allergy-related
core alpha1,3-fucosyltransferase and the first insect Lewis-histo-blood-group
related antigen-synthesizing enzyme.
AB - Glycoproteins from honey-bee (Apis mellifera), such as phospholipase A2 and
hyaluronidase, are well-known major bee-venom allergens. They carry N-linked
oligosaccharide structures with two types of alpha1,3-fucosylation: the
modification by alpha1,3-fucose of the innermost core GlcNAc, which constitutes
an epitope recognized by IgE from some bee-venom-allergic patients, and an
antennal Lewis-like GalNAcbeta1,4(Fucalpha1,3)GlcNAc moiety. We now report the
cloning and expression of two cDNAs encoding the relevant active alpha1,3-FucTs
(alpha1,3-fucosyltransferases). The first sequence, closest to that of fruitfly
(Drosophila melanogaster) FucTA, was found to be a core alpha1,3-FucT (EC
2.4.1.214), as judged by several enzyme and biochemical assays. The second cDNA
encoded an enzyme, most related to Drosophila FucTC, that was shown to be capable
of generating the Le(x) [Galbeta1-4(Fucalpha1-3)GlcNAc] epitope in vitro and is
the first Lewis-type alpha1,3-FucT (EC 2.4.1.152) to be described in insects. The
transcription levels of these two genes in various tissues were examined: FucTA
was found to be predominantly expressed in the brain tissue and venom glands,
whereas FucTC transcripts were detected at highest levels in venom and
hypopharyngeal glands. Very low expression of a third homologue of unknown
function, FucTB, was also observed in various tissues. The characterization of
these honey-bee gene products not only accounts for the observed alpha1,3
fucosylation of bee-venom glycoproteins, but is expected to aid the
identification and subsequent down-regulation of the FucTs in insect cell lines
of biotechnological importance.
PMID- 17029594
TI - Neuron-astrocyte interactions in the regulation of brain energy metabolism: a
focus on NMR spectroscopy.
AB - An adequate and timely production of ATP by brain cells is of cardinal importance
to support the major energetic cost of the rapid processing of information via
synaptic and action potentials. Recently, evidence has been accumulated to
support the view that the regulation of brain energy metabolism is under the
control of an intimate dialogue between astrocytes and neurons. In vitro studies
on cultured astrocytes and in vivo studies on rodents have provided evidence that
glutamate and Na(+) uptake in astrocytes is a key triggering signal regulating
glucose use in the brain. With the advent of NMR spectroscopy, it has been
possible to provide experimental evidence to show that energy consumption is
mainly devoted to glutamatergic neurotransmission and that glutamate-glutamine
cycling is coupled in a approximately 1 : 1 molar stoichiometry to glucose
oxidation, at least in the cerebral cortex. This improved understanding of neuron
astrocyte metabolic interactions offers the potential for developing novel
therapeutic strategies for many neurological disorders that include a metabolic
deficit.
PMID- 17029593
TI - RNA interference in pain research.
AB - Within the course of only the last few years, RNA interference (RNAi) has been
established as a standard technology for investigation of protein function and
target validation. The present review summarizes recent progress made in the
application of RNAi in neurosciences with special emphasis on pain research. RNAi
is a straightforward method to generate loss-of-function phenotypes for any gene
of interest. In mammals, silencing is induced by small interfering RNAs (siRNAs),
which have been shown to surpass traditional antisense molecules. Due to its high
specificity, RNAi has the potential for subtype selective silencing of even
closely related genes. One of the major challenges for in vivo investigations of
RNAi remains efficient delivery of siRNA molecules to the relevant tissues and
cells, particularly to the central nervous system. Various examples will be given
to demonstrate that intrathecal application of siRNAs is a suitable approach to
analyse the function of receptors or other proteins that are hypothesized to play
an important role in pain signalling. Intensive efforts are currently ongoing to
solve remaining problems such as the risk of off-target effects, the stability of
siRNA molecules and their efficient delivery to the CNS. RNAi has thus
demonstrated that it is an extremely valuable tool for the development of new
analgesic drugs.
PMID- 17029595
TI - Microtubules are required for NF-kappaB nuclear translocation in neuroblastoma
IMR-32 cells: modulation by zinc.
AB - The relevance of a functional cytoskeleton for Nuclear Factor-kappaB (NF-kappaB)
nuclear translocation was investigated in neuronal cells, using conditions that
led to a disruption of the cytoskeleton [inhibition of tubulin (vinblastine,
colchicine), or actin (cytochalasin D) polymerization and zinc deficiency]. We
present evidence that an impairment in tubulin polymerization can inhibit the
formation of the complex tubulin-dynein-karyopherin alpha-p50 that is required
for neuronal retrograde and nuclear NF-kappaB transport. Cells treated with
vinblastine, colchicine or cytochalasin D, and zinc deficient cells, all showed a
low nuclear NF-kappaB binding activity, and low nuclear concentrations of RelA
and p50. The altered nuclear translocation was reflected by a decreased
transactivation of NF-kappaB-driven genes. The immunocytochemical
characterization of cellular RelA showed that cytoskeleton disruption can lead to
an altered distribution of RelA resulting in the formation of peripheral
accumuli. These results support the concept that cytoskeleton integrity is
necessary for the transport and translocation of NF-kappaB required for synapse
to nuclei communication. We suggest that during development, as well as in the
adult brain, conditions such as zinc deficiency, that affect the normal structure
and function of the cytoskeleton can affect neuronal proliferation,
differentiation, and survival by altering NF-kappaB nuclear translocation and
subsequent impairment of NF-kappaB-dependent gene regulation.
PMID- 17029596
TI - Differential effect of nerve growth factor on dopaminergic neurotoxin-induced
apoptosis.
AB - Both rotenone and manganese are possible neurotoxins for a wide variety of cell
and neuronal types including dopaminergic neurons and induce apoptosis in various
cells. Neurotrophic factors have the potential for therapeutic development when
used to prevent Parkinson's disease. In this paper, we focused on the differences
between rotenone and manganese as toxins, and characterized the influence of
neurotrophic factors on toxin-induced apoptosis in PC12 cells. There were
distinct differences in intracellular mechanisms between rotenone- and manganese
induced apoptosis such as the production of reactive oxygen species, the response
to antioxidants, and the activation of the c-Jun N-terminal kinase (JNK) and p38
mitogen-activated protein kinase (MAPK). Nerve growth factor (NGF) almost
completely prevented rotenone-induced but not manganese-induced caspase
activation and DNA fragmentation. The differential effect of NGF was found to be
mainly due to the down-regulation of the Trk tyrosine kinase receptor by
manganese but not by rotenone. Prevention of rotenone-induced apoptosis by NGF
was attenuated by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor,
LY294002, but not MAPK kinase (MEK) inhibitors, PD98059 or U0126. These results
demonstrate that the potential neurotoxins for dopaminergic cells exert their
toxic effect by activation of different signaling pathways of apoptosis and that
NGF prevents rotenone-induced apoptosis through the activation of the PI 3-kinase
pathway not MAPK pathway.
PMID- 17029597
TI - Selective blockage of Kv1.3 and Kv3.1 channels increases neural progenitor cell
proliferation.
AB - The modulation of cell proliferation in neural progenitor cells (NPCs) is
believed to play a role in neuronal regeneration. Recent studies showed that K(+)
channel activity influenced cell proliferation. Therefore, we examined NPCs for
K(+) channels and tested whether NPC self renewing can be modulated by synthetic
K(+) channel modulators. The whole-cell K(+) current was partly K(+) dependent
and showed a cumulative inactivating component. Two tetra-ethyl-ammonium ion
(TEA)-sensitive K(+) currents with different voltage dependencies ( = 65 microm,
E(50) = -0.3 +/- 1.3 mV and = 8 mm, E(50) = -15.2 +/- 2.8 mV) and an almost TEA
insensitive current were identified. Kaliotoxin blocked approximately 50% of the
entire K(+) currents (IC(50) = 0.25 nm). These properties resembled functional
characteristics of K(v)1.4, K(v)1.3 and K(v)3.1 channels. Transcripts for these
channels, as well as proteins for K(v)1.3 and K(v)3.1, were identified.
Immunocytochemical staining revealed K(v)1.3 and K(v)3.1 K(+) channel expression
in almost all NPCs. The blockage of K(v)3.1 by low concentrations of TEA, as well
as the blockage of K(v)1.3 by Psora-4, increased NPC proliferation. These
findings underline the regulatory role of K(+) channels on the cell cycle and
imply that K(+) channel modulators might be used therapeutically to activate
endogenous NPCs.
PMID- 17029598
TI - Deposition of iron and beta-amyloid plaques is associated with cortical cellular
damage in rabbits fed with long-term cholesterol-enriched diets.
AB - Hypercholesterolemia is a potential trigger of Alzheimer's disease, and is
thought to increase brain levels of beta-amyloid (Abeta) and iron. However,
animal models to address the mechanisms by which Abeta and iron accumulation may
cause neuronal damage are poorly defined. To address this question, we fed adult
rabbits a 1% cholesterol-enriched diet for 7 months. This diet was associated
with increased regional deposition of both iron and Abeta peptide in the brain.
Iron preferentially accumulated around Abeta plaques in the adjacent cortex, but
was not found in the hippocampus. Co-localization of iron and Abeta was
accompanied by apoptosis, DNA damage, blood-brain barrier (BBB) disruption, as
well as dysregulation in the level of the iron-regulatory proteins, ferritin and
heme-oxygenase-1. We further demonstrate that the cholesterol diet-induced
apoptosis is mediated by the activation of the endoplasmic reticulum stress
pathway, involving the down-regulation of the endoplasmic reticulum chaperones,
calreticulin, grp78 and grp94, and the activation of the growth and arrest DNA
damage protein, gadd153. Our results suggest that BBB damage and disturbances in
iron metabolism may render the cortex more vulnerable than the hippocampus to the
cholesterol-induced cellular stress.
PMID- 17029599
TI - Identification of a new functional target of haloperidol metabolite: implications
for a receptor-independent role of 3-(4-fluorobenzoyl) propionic acid.
AB - Haloperidol, a dopamine D2 receptor blocker, is a classical neuroleptic drug that
elicits extrapyramidal symptoms. Its metabolites include 3-(4-fluorobenzoyl)
propionic acid (FBPA) and 4-(4-chlorophenyl)-4-piperidinol (CPHP). Until now, the
biological significance of these metabolites has remained largely unknown. Here,
we report that the administration of FBPA to mice effected a suppression of
locomotor activity and induced catalepsy in a manner similar to that observed
with haloperidol, whereas CPHP had no significant effects. Neither of these two
metabolites, however, exhibited any ability to bind to the dopamine D2 receptor.
FBPA blocked dopamine-induced extracellular signal-regulated kinase 1/2
phosphorylation, and it specifically affected mitogen-activated protein kinase
kinase (MEK)1/2 activity in hippocampal HN33 cells. Moreover, FBPA was capable of
direct interaction with MEK1/2, and inhibited its activity in vitro. We
demonstrated the generation of haloperidol metabolites within haloperidol-treated
cells by mass spectrometric analyses. Collectively, our results confirm the
biological activity of FBPA, and provide initial clues as to the receptor
independent role of haloperidol.
PMID- 17029600
TI - Regulation of alpha-synuclein expression in alcohol-preferring and -non
preferring rats.
AB - The alpha-synuclein (Snca) gene is expressed at higher levels in alcohol-naive,
inbred alcohol-preferring (iP) rats than in alcohol-non preferring (iNP) rats.
Snca modulates dopamine transmission and the dopamineregic system, which play a
role in mediating the rewarding properties of alcohol consumption. Thus,
understanding regulation of Snca gene expression could provide insight into the
relationship of Snca and alcohol consumption. To study regulation of rat Snca
expression, 1,912 bp of the iP and iNP 5'-regions were cloned and sequenced. 5'
rapid amplification of cDNA ends (RACE), primer extension and RT-PCR mapped three
transcription start site clusters (clusters TSS1, TSS2 and TSS3), suggesting that
the Snca proximal promoter region has a complex architecture. This proximal
promoter region has three TATA-less core promoters containing SP1 binding sites,
initiator elements and downstream core promoter elements, which are often located
in such promoters. Snca-luc constructs transiently transfected into SK-N-SH
neuroblastoma cells showed that the region from - 1,912 to - 1,746 contained a
strong core promoter, and that the entire approximately 2 kb region had
significant promoter activity. Five polymorphisms identified between the iP and
iNP in the proximal promoter region did not influence differential expression
between the strains. In contrast, a single nucleotide polymorphism (SNP) at + 679
in the 3'-untranslated region (UTR) resulted in a 1.3-fold longer half-life of iP
mRNA compared with iNP mRNA, which is consistent with the differential expression
observed between the iP and iNP strains. These results suggest that regulation of
rat Snca gene expression is complex and may contribute to alcohol preference in
the iP rats.
PMID- 17029601
TI - Nitric oxide production in the basal forebrain is required for recovery sleep.
AB - Sleep homeostasis is the process by which recovery sleep is generated by
prolonged wakefulness. The molecular mechanisms underlying this important
phenomenon are poorly understood. Here, we assessed the role of the intercellular
gaseous signaling agent NO in sleep homeostasis. We measured the concentration of
nitrite and nitrate, indicative of NO production, in the basal forebrain (BF) of
rats during sleep deprivation (SD), and found the level increased by 100 +/- 51%.
To test whether an increase in NO production might play a causal role in recovery
sleep, we administered compounds into the BF that increase or decrease
concentrations of NO. Infusion of either a NO scavenger, 2-(4-carboxyphenyl)
4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, or a NO synthase inhibitor,
N(omega)-nitro-L-arginine methyl ester (L-NAME), completely abolished non-rapid
eye movement (NREM) recovery sleep. Infusion of a NO donor, (Z)-1-[N-(2
aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2diolate (DETA/NO), produced
an increase in NREM that closely resembled NREM recovery after prolonged
wakefulness. The effects of inhibition of NO synthesis and the pharmacological
induction of sleep were effective only in the BF area. Indicators of energy
metabolism, adenosine, lactate and pyruvate increased during prolonged
wakefulness and DETA/NO infusion, whereas L-NAME infusion during SD prevented the
increases. We conclude that an increase in NO production in the BF is a causal
event in the induction of recovery sleep.
PMID- 17029602
TI - Noncompensation in peptide/receptor gene expression and distinct behavioral
phenotypes in VIP- and PACAP-deficient mice.
AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
intestinal peptide (VIP) are closely related neurotrophic peptides of the
secretin/glucagon family. The two peptides are derived from a common ancestral
gene and share many functional attributes in neuronal development/regeneration
which occur not only from overlapping receptor subtype signaling but also through
common mechanisms regulating their expression. Although PACAP or VIP null mice
have been generated for study, it is unclear whether the expression of the
complementary peptide or their receptor systems are altered in a compensatory
manner during nervous system development. By radioimmunoassay and quantitative
PCR measurements, we first show that PACAP and VIP have very different temporal
patterns of expression in developing postnatal mouse brain. In wild-type animals,
PACAP transcript and peptide levels increased rapidly 2- and 5-fold,
respectively, within 1 week of age. These levels at 1 week of age were maintained
through adulthood. VIP transcript and peptide levels, by contrast, increased 25-
and 50-fold, respectively, over a later time course. In parallel studies of
development, there were no apparent compensatory increases in brain VIP
expression in the PACAP knockout animals, PACAP expression in the VIP-deficient
animals, or receptor mRNA levels in either genotype. To the contrary, there was
evidence for developmental delays in the expression of peptide and receptor
transcripts in the knockout animals. A series of behavioral and neurological
tests demonstrated differences between the knockout genotypes, revealing some
functional distinctions between the two genes. These results suggest that the
PACAP and VIP have evolved to possess distinct biological activities and intimate
that the respective knockout phenotypes represent deficits unmitigated by the
actions of the complementary related peptide.
PMID- 17029603
TI - Astrocyte swelling leads to membrane unfolding, not membrane insertion.
AB - The mechanisms mediating the release of chemical transmitters from astrocytes are
the subject of intense research. Recent experiments have shown that hypotonic
conditions stimulate the release of glutamate and ATP from astrocytes, but a
mechanistic understanding of this process is not available. To determine whether
hypotonicity activates the process of regulated exocytosis, we monitored membrane
capacitance by the whole-cell patch-clamp technique whilst a hypotonic medium was
applied to cultured astrocytes. If exocytosis is triggered under hypotonic
conditions, as it is following increases in cytosolic calcium, a net increase in
membrane surface area, monitored by measuring the whole-cell membrane
capacitance, is expected. Simultaneous measurements of cell size and whole-cell
membrane conductance and surface area demonstrated that hypotonic medium (210
mOsm for 200 s) resulted in an increase in membrane conductance and in the
swelling of cultured astrocytes by an average of 40%, as monitored by cell cross
sectional area, but without any corresponding change in membrane surface area. As
we have demonstrated that capacitance measurements have the sensitivity to detect
increases in cell surface area as small as 0.5%, we conclude that cell swelling
occurs via an exocytosis-independent mechanism, probably involving the unfolding
of the plasma membrane.
PMID- 17029604
TI - Proinsulin/insulin is synthesized locally and prevents caspase- and cathepsin
mediated cell death in the embryonic mouse retina.
AB - Programmed cell death is an essential, highly regulated process in neural
development. Although the role of insulin-like growth factor I in supporting the
survival of neural cells has been well characterized, studies on
proinsulin/insulin are scarce. Here, we characterize proinsulin/insulin effects
on cell death in embryonic day 15.5 mouse retina. Both proinsulin mRNA and
proinsulin/insulin immunoreactivity were found in the developing retina.
Organotypic embryonic day 15.5 retinas cultured under growth factor deprivation
showed an increase in cell death that was reversed by proinsulin, insulin and
insulin-like growth factor I, with similar median effective concentration values
via phosphatidylinositol-3-kinase activation. Although insulin and insulin-like
growth factor I provoked a sustained Akt phosphorylation, proinsulin-induced
phosphorylation of Akt was not found. Analysis of the growth factor deprivation
induced cell death mechanisms, using caspase and cathepsin inhibitors,
demonstrated that both protease families were required for the effective
execution of cell death. The insulin survival effect, which decreased the extent
and distribution of cell death to levels similar to those found in vivo, was not
enhanced by simultaneous treatment with caspase and cathepsin inhibitors,
suggesting that insulin interferes with these protease pathways in the embryonic
mouse retina. The mechanisms characterized in this study provide new details on
early neural cell death and its genuine regulation by insulin/proinsulin.
PMID- 17029605
TI - Hierarchy and the mechanism of fibril formation in ADan peptides.
AB - Familial Danish dementia is a neurodegenerative disease which is a consequence of
alterations in the BRI gene. The pathological signatures of the disease are
cerebral amyloidolysis, parenchymal protein deposits and neuronal degeneration.
Synthetic Danish dementia (ADan) peptides are capable of forming fibrillar
assemblies in vitro at pH 4.8. However, the morphology of the aggregates formed
depends greatly on the form of the peptides (oxidized or reduced). In addition to
long slender assemblies (2-5 nm in diameter and several micrometers in length) we
report ring-like or annular masses (8-9 nm in diameter and 1-2 mm in perimeter)
in the case of the oxidized form of the peptides. The reduced forms mainly
aggregate to produce granular heaps. The biophysical and kinetic characterization
of the process of aggregation was carried out using different spectroscopic and
imaging techniques. Neurotoxicity assays performed on both the forms reveal that
the toxicity bears proportionality with the aggregate size.
PMID- 17029606
TI - Noxp20 and Noxp70, two new markers of early neuronal differentiation, detected in
teratocarcinoma-derived neuroectodermic precursor cells.
AB - The murine 1C11 cell line, derived from F9 pluripotent teratocarcinoma cells,
exhibits features of a bipotential neuronal precursor as it converts into
serotonergic or catecholaminergic neurons under appropriate induction. In order
to point out molecular markers expressed in this early neuroectodermic
commitment, we used a cDNA subtractive hybridization method. The 105 different
isolated cDNAs represented 75 known genes, expressed sequence tags (EST) or
genomic fragments. A majority of known proteins encoded by these sequences are
involved in cellular mobility or migration. We characterized two sequences
showing identities with ESTs and we called them Noxp20 and Noxp70. The Noxp20
transcript encodes a putative protein with a predicted caspase recruitment domain
and the Noxp70 transcript encodes a putative protein displaying a Zn-finger
domain. Consistent with their roles in neuronal cell development, in situ
hybridization showed that Noxp20 and Noxp70 are over-expressed in brain. At
embryonic days 12 and 15, Noxp20 is strongly expressed in the ventricular and
intermediate zones of the brain and of the spinal cord. At embryonic day 15,
Noxp70 was found to be strongly expressed in the ventricular zone around the
telencephalic ventricle, and to a lower extent in the thalamus and hypothalamus.
At post-natal day 10, Noxp20 mRNA was detected in the dentate gyrus, the
hippocampus, the cerebellum and the olfactory bulb.
PMID- 17029607
TI - Platelet count/spleen diameter ratio for the noninvasive diagnosis of esophageal
varices: results of a multicenter, prospective, validation study.
AB - BACKGROUND AND AIMS: Noninvasive assessment of esophageal varices (EV) may
improve the management of patients with cirrhosis and decrease both the medical
and financial burden related to screening. In this multicenter, international
study, our aim was to prospectively validate the use of the platelet count/spleen
diameter ratio for the noninvasive diagnosis of EV. METHODS: A total of 218
cirrhotic patients underwent screening endoscopy for EV. Platelet count/spleen
diameter ratio ((N/mm3)/mm) was assessed in all patients and its diagnostic
accuracy was calculated. On the basis of previous results, a platelet
count/spleen diameter ratio cutoff of 909 was applied to this population. The
diagnostic accuracy of the platelet count/spleen diameter ratio was further
evaluated for both severity and etiology of disease subgroups. RESULTS:
Prevalence of EV was 54.1%. The platelet count/spleen diameter ratio had 86.0%
(95% CI, 80.7-90.4%) diagnostic accuracy for EV, which was significantly greater
as compared with either accuracy of platelet count alone (83.6%, 95% CI 78.0
88.3%, P= 0.038) or spleen diameter alone (80.2%, 95% CI 74.3-85.3%, P= 0.018).
The 909 cutoff had 91.5% sensitivity (95% CI 85.0-95.9%), 67.0% specificity (95%
CI 56.9-76.1%), 76.6% positive predictive value, 87.0% negative predictive value,
2.77 positive likelihood ratio, and 0.13 negative likelihood ratio for the
diagnosis of EV. Accuracy of the platelet count/spleen diameter ratio was
maintained for both severity and etiology of disease subgroups. CONCLUSIONS: The
platelet count/spleen diameter ratio may be proposed as a safe and reproducible
means to improve the management of cirrhotic patients who should undergo
screening endoscopy for EV.
PMID- 17029608
TI - Physical activity and intestinal gas clearance in patients with bloating.
AB - BACKGROUND: Patients complaining of abdominal bloating have impaired tolerance
and clearance of intestinal gas loads. Mild exercise enhances intestinal
clearance and prevents retention of intestinal gas loads in healthy subjects. Our
aim was to evaluate the putative beneficial effects of physical activity in
patients with abdominal bloating. METHODS: In eight patients complaining of
bloating, seven with irritable bowel syndrome, and one with functional bloating,
according to Rome II criteria, a gas mixture was continuously infused (12 mL/min)
into the jejunum for 120 min with simultaneous duodenal lipid perfusion (1
kcal/min). Gas evacuation, perception (0-6 scale), and abdominal girth were
measured at 15-min intervals. Paired studies were randomly performed in the
supine position during intermittent pedaling (5 min with 3-min rest intervals at
40 rpm and 0.15 kp load) versus rest (as control). RESULTS: During rest, a
significant proportion of the gas infused was retained in the gut (45 +/- 9%, P <
0.01 vs basal), but retention was significantly lower during exercise (24 +/- 7%,
P < 0.05 vs rest). Gas retention during rest was associated with significant
abdominal symptoms (3.6 score; P < 0.01 vs basal), and symptoms also improved
during exercise (2.8 score, P < 0.05 vs rest). During the test, patients
developed abdominal distension, which was related to the volume of gas retained
(r = 0.68, P < 0.05). CONCLUSION: Mild physical activity enhances intestinal gas
clearance and reduces symptoms in patients complaining of abdominal bloating.
PMID- 17029609
TI - Prospective follow-up data from the ProGERD study suggest that GERD is not a
categorial disease.
AB - OBJECTIVES: There is a controversy as to whether gastroesophageal reflux disease
(GERD) exists as a spectrum of disease severity or as a categorial disease in
three distinct groups: nonerosive (NERD) and erosive reflux disease (ERD) and
Barrett's esophagus (BE). Aim of the study was to assess progression or
regression of GERD over 2 yr in a large cohort of patients (N = 3,894) under
routine clinical care in Germany, Austria, and Switzerland (ProGERD study).
METHOD: Patients with predominant heartburn, with or without esophagitis, were
recruited and classified according to endoscopic status at baseline, i.e., NERD,
erosive reflux disease-Los Angeles (ERD-LA) grade A/B and ERD-LA grade C/D, and
BE. After an initial treatment with esomeprazole, they were followed, regardless
of their response. Medical therapy or endoscopy was initiated at the discretion
of their primary care physician, in line with routine care. At 2 yr, endoscopy
with biopsy was performed according to the protocol. RESULTS: After 2 yr, 25% of
patients who had NERD at baseline progressed to LA A/B and 0.6% to LA C/D; 1.6%
of patients who had LA A/B progressed to LA C/D and 61% regressed to NERD; 42% of
patients who had LA C/D regressed to LA A/B and 50% regressed to NERD (all
figures exclude patients with confirmed BE at baseline). At 2 yr, 22% of patients
had been off medication for at least 3 months. Patients with ERD-LA grade C/D
were at greatest risk of developing BE: 5.8% compared with 1.4% for ERD-LA grade
A/B and 0.5% for NERD. CONCLUSION: GERD does not seem to be a categorial disease.
Progression and regression between grades was observed in this large cohort of
patients under routine clinical care.
PMID- 17029610
TI - Successful treatment with peginterferon alfa-2b of HBeAg-positive HBV non
responders to standard interferon or lamivudine.
AB - OBJECTIVES: Antiviral therapy leads to HBeAg seroconversion in 10-40% of the
patients with HBeAg-positive chronic hepatitis B. Nonresponse may result in
progression of liver disease and increased risk of hepatocellular carcinoma. As
part of a global randomized controlled trial we investigated the efficacy (i.e.,
loss of HBeAg at the end of follow-up) of peginterferon alfa-2b (Peg-IFN alpha2b)
in patients who failed to respond to previous courses of standard interferon
(IFN) or lamivudine. METHODS: We analyzed a total of 76 previous nonresponders:
37 were nonresponders to standard IFN, 17 were nonresponders to lamivudine, and
22 were nonresponders to both therapies. All patients received a 52-wks course of
100 microg Peg-IFN alpha2b weekly combined with either 100 mg lamivudine daily or
a placebo. After therapy patients were followed for 26 wks. RESULTS: Thirteen
(35%) nonresponders to previous IFN, five (29%) nonresponders to previous
lamivudine, and four (22%) nonresponders to both IFN and lamivudine responded to
treatment with Peg-IFN alpha2b. No difference in response was found for those
treated with Peg-IFN alpha2b alone or in combination with lamivudine.
Nonresponders to prior IFN therapy with baseline ALT (alanine aminotransferase) >
4 x ULN (upper limit of normal) responded better to Peg-IFN alpha2b than those
with ALT levels or=3) and
inflammation (Ishak grade >or=7). RESULTS: In HBeAg negative patients significant
liver fibrosis was best predicted using the variables HBV DNA levels, alkaline
phosphatase, albumin, and platelet counts with an area under ROC curve (AUC) of
0.91 for the training group and 0.85 for the validation group. Using the low
cutoff probability of 4.72, significant fibrosis could be excluded with negative
predictive value of 99% in the entire cohort, and liver biopsy would have been
avoided in 52% of patients. The best model for predicting significant
inflammation included the variables age, HBV DNA levels, AST, and albumin with an
AUC of 0.93 in the training and 0.82 in the validation group. In HBeAg positive
patients no factor could predict accurately stages of liver fibrosis, but the
best factor for predicting significant inflammation was AST with an AUC of 0.87.
CONCLUSIONS: Significant hepatic fibrosis and necroinflammation can reliably be
predicted using routinely checked tests and HBV DNA levels.
PMID- 17029617
TI - Noncardia gastric adenocarcinoma remains an important and deadly cancer in the
United States: secular trends in incidence and survival.
AB - BACKGROUND: Noncardia gastric adenocarcinoma is not frequently mentioned in the
United States. However, it is unclear if the previously reported decline in
noncardia gastric adenocarcinoma has continued, and if detection and management
has affected overall survival outside the setting of clinical trials. METHODS: We
used the Surveillance, Epidemiology, and End Results registry (SEER) to identify
all cases of noncardia gastric adenocarcinoma diagnosed between 1973 and 2002.
The yearly age-adjusted incidence rates and the relative survival rates were
calculated. Cox proportional hazards (PH) models were used to examine temporal
trends from 1983 to 2003. RESULTS: Between 1973 and 2002, there were 24,103 cases
of noncardia gastric adenocarcinoma. The age-adjusted yearly incidence rate
declined by 23% between 1973 and 2002 from 4.3 to 3.3 per 100,000 person-years.
However, the incidence of localized noncardia gastric adenocarcinoma (invasive
neoplasm confined to the organ of origin) remained without change between 0.9 and
1.0 per 100,000 person-years, and increased with age, especially in the 85+ yr
age group (a 47% increase between 1973 and 2002). The incidence rates in men were
double those in women, and 1.6-fold and 2.6-fold higher in blacks and other races
(mostly Asians), respectively, compared with whites. Patients with radiation and
chemotherapy after gastrectomy had a 22% better mortality risk compared with
those treated with gastrectomy alone. The Cox PH analysis shows no significant
change in mortality risk related to year of diagnosis between 1983 and 2002, both
in unadjusted as well as adjusted analyses. However, there were significant
independent regional and racial variations in survival. Asians had a 17% lower
mortality risk compared with whites. CONCLUSIONS: Despite the overall decline in
noncardia gastric adenocarcinoma, the incidence of local stage disease has
remained stable in most ages and even increased in old ages. Unfortunately, there
has been no significant improvement in survival during the past 20 yr. Moreover,
there remain considerable regional as well as racial variations in mortality.
PMID- 17029619
TI - Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate
malignant and benign pancreatic masses.
AB - OBJECTIVES: Accurate diagnosis of malignant and benign pancreatic masses can be
challenging, potentially delaying treatment for cancer and subjecting patients
with benign disease to unnecessary surgery. Endoscopic ultrasound fine needle
aspirate (EUS-FNA) of pancreatic masses remains inconclusive in a subset of
patients. The role of EUS-FNA molecular analysis in this context is studied.
METHODS: Patients with benign pancreatic masses (6 cases, 4 autoimmune
pancreatitis, 2 focal chronic pancreatitis) and malignant pancreatic masses (15)
with inconclusive cytology (5 cases) and positive cytology (10 controls) were
selected. All cases had definitive pathology. Representative cells were
microdissected from each EUS-FNA sample and subjected to PCR for analysis of 16
microsatellite allele loss markers situated at 1p, 3p, 5q, 9p, 9q, 10q, 17p, 17q,
21q, and 22q. Loss of heterozygosity analysis used fluorescent capillary
electrophoresis for quantitative determination of allelic imbalance. k-ras-2
point mutation analysis was also performed. Mean fractional mutation rate (FMR)
was calculated and compared for each group. RESULTS: All malignant cases carried
multiple mutations (FMR 0.50), regardless of positive cytology (FMR 0.52) or
suspicious cytology (FMR 0.47) (p = NS). Five of the 6 benign cases carried no
mutations whereas 1 case of autoimmune pancreatitis and coexisting PanIN lesions
exhibited a k-ras mutation (FMR 0.01). The mean FMR for the malignant and benign
samples was significantly different (p < 0.0001). CONCLUSIONS: Broad panel
microsatellite loss and k-ras point mutation analysis can be reliably performed
on EUS-FNA samples from pancreatic masses and improves the diagnostic accuracy.
Furthermore, it accurately differentiates between malignant and benign pancreatic
masses.
PMID- 17029618
TI - Safety and colon-cleansing efficacy of a new residue-free formulation of sodium
phosphate tablets.
AB - OBJECTIVE: A residue-free sodium phosphate tablet (RF-NaP) was formulated that
lacks microcrystalline cellulose, which can appear as a whitish residue in the
colon. A multicenter, randomized, investigator-blinded study was conducted to
compare the colon-cleansing efficacy of 40 or 32 tablets of RF-NaP with the
marketed 40-tablet NaP treatment regimen. METHODS: Eight hundred sixteen patients
were randomized prior to colonoscopy to receive either 40 tablets (60 g) of NaP
or RF-NaP or 32 tablets (48 g) of RF-NaP. Colon cleansing was assessed using a 4
point scale based on retained "colonic contents." The primary end point was
overall colon-cleansing response rate to treatment (score of excellent/good)
versus nonresponse (fair/inadequate). RESULTS: Seven hundred four patients were
included in the efficacy analysis. The overall colon-cleansing response rates
were comparable among treatment arms (94.5%, 97.0%, and 95.3% for NaP, RF-NaP 40,
and RF-NaP 32 tablets, respectively). Ascending colon-cleansing response rates
for RF-NaP 40 (95.7%) and 32 tablets (93.6%) were significantly better than for
NaP tablets (88.5%, p < 0.03 for both). Patients treated with RF-NaP 32 tablets
experienced less pronounced changes in electrolyte levels and fewer adverse
events (138/239, 58%) compared with patients receiving NaP (161/238, 68%, p=
0.07) and RF-NaP 40 tablets (156/236, 66%, p= 0.03). The most common adverse
events reported were abdominal distention, nausea, abdominal pain, and vomiting.
CONCLUSIONS: Based on the safety, efficacy, and patient preferences, the 32
tablet RF-NaP regimen was superior to the 40-tablet RF-NaP and NaP regimen for
colon cleansing prior to colonoscopy.
PMID- 17029620
TI - Biliary tract candidiasis: diagnostic and therapeutic approaches in a case
series.
AB - BACKGROUND: Biliary obstruction with its wide range of potential causes is a
common disorder in gastroenterology. Infections of the biliary tract with Candida
and other fungal species leading to obstructive jaundice have increasingly been
recognized in the last few years. Besides a few case reports, there are few data
in the literature giving us an idea how to diagnose and treat these patients.
METHODS: We report on a series of seven patients suffering from biliary tract
candidiasis who were diagnosed and treated at our institution. Predisposition
factors, reliability of various diagnostic modalities, and treatment options
based on our own experience are presented and discussed. RESULTS: Besides the
general diagnostic modalities such as laboratory findings or ultrasonography, we
often observed mycelia in the bile duct system endoscopically. Typical
morphological changes in peripheral bile ducts could be detected during
endoscopic retrograde cholangiopancreatography (ERCP). Aspiration of bile and
subsequent microbiological analysis in combination with ERCP findings revealed
diagnosis of bile duct candidiasis in all cases. Treatment included both
antiinfectious drugs and endoscopic therapy such as bile duct drainage, lavage,
or debridement. With respect to fungal eradication, therapy was successful in 71%
of cases as proven by microbiological analysis of bile aspirates. Since many of
these patients suffer not only from biliary mycosis but also from disease
necessitating immunosuppression, the prognosis was poor in some cases.
CONCLUSION: Biliary tract candidiasis because of immunosuppression is an
increasingly recognized disease and remains a major clinical challenge. Besides
laboratory analysis and ultrasonography, diagnostic modalities should include
aspiration of bile during ERCP and microbiological analysis. Antiinfectious drug
treatment as the main therapeutic column for biliary candidiasis should be
complemented by endoscopic intervention.
PMID- 17029621
TI - Predicting iron and folate deficiency anaemias from standard blood testing: the
mechanism and implications for clinical medicine and public health in developing
countries.
AB - BACKGROUND: Developing countries have high prevalence of diseases, but facilities
to diagnose and treat them are limited. We must use available resources in ways
not needed where there are sophisticated equipment and trained staff. Anaemia is
common; iron deficiency affects health and productivity; folate deficiency in
pregnant women causes foetal abnormalities. Few developing countries can measure
serum folate or ferritin, but standard automated blood analyses are widely
available and can help predict folate and iron deficiency. The RDW-CV%
(coefficient of variation of the red cell width) measures the variability in the
size of red blood cells (RBC) in routine automated analysis of blood cells, but
is seldom reported. Levels of RDW-CV% and haemoglobin (Hb) can predict iron
deficiency anaemia. METHOD AND RESULTS: I have written a computer model based on
the standard mechanism for blood formation and destruction. This shows that
before anaemia develops and during recovery, there are both normal and abnormal
RBC (small in iron deficiency and large in folate deficiency) in the circulation.
The model calculates the abnormality in the RDW-CV% in standard automated blood
analyses. In early iron deficiency and during recovery the full blood count shows
the Hb near the lower limit of normal, a low MCV and a high RDW-CV%. A similar
pattern, but with a higher MCV, develops in folate deficiency. Folate deficiency
is often brief and may not cause anaemia. The high RDW-CV% may persist for three
months. CONCLUSION: This long footprint could be medically useful for detecting
folate deficiency and so limiting foetal damage in individuals and communities.
Few clinicians or public health workers know about RDW-CV%. Standard blood
reports for clinical use should include the RDW-CV% and note the possible
significance of abnormal values.
PMID- 17029622
TI - Timing and risk factors for clinical fractures among postmenopausal women: a 5
year prospective study.
AB - BACKGROUND: Many risk factors for fractures have been documented, including low
bone-mineral density (BMD) and a history of fractures. However, little is known
about the short-term absolute risk (AR) of fractures and the timing of clinical
fractures. Therefore, we assessed the risk and timing of incident clinical
fractures, expressed as 5-year AR, in postmenopausal women. METHODS: In total, 10
general practice centres participated in this population-based prospective study.
Five years after a baseline assessment, which included clinical risk factor
evaluation and BMD measurement, 759 postmenopausal women aged between 50 and 80
years, were re-examined, including undergoing an evaluation of clinical fractures
after menopause. Risk factors for incident fractures at baseline that were
significant in univariate analyses were included in a multivariate Cox survival
regression analysis. The significant determinants were used to construct
algorithms. RESULTS: In the total group, 12.5% (95% confidence interval (CI) 10.1
14.9) of the women experienced a new clinical fracture. A previous clinical
fracture after menopause and a low BMD (T-score <-1.0) were retained as
significant predictors with significant interaction. Women with a recent previous
fracture (during the past 5 years) had an AR of 50.1% (95% CI 42.0-58.1) versus
21.2% (95% CI 20.7-21.6) if the previous fracture had occurred earlier. In women
without a fracture history, the AR was 13.8% (95% CI 10.9-16.6) if BMD was low
and 7.0% (95% CI 5.5-8.5) if BMD was normal. CONCLUSION: In postmenopausal women,
clinical fractures cluster in time. One in two women with a recent clinical
fracture had a new clinical fracture within 5 years, regardless of BMD. The 5
year AR for a first clinical fracture was much lower and depended on BMD.
PMID- 17029623
TI - A model of gene-gene and gene-environment interactions and its implications for
targeting environmental interventions by genotype.
AB - BACKGROUND: The potential public health benefits of targeting environmental
interventions by genotype depend on the environmental and genetic contributions
to the variance of common diseases, and the magnitude of any gene-environment
interaction. In the absence of prior knowledge of all risk factors, twin, family
and environmental data may help to define the potential limits of these benefits
in a given population. However, a general methodology to analyze twin data is
required because of the potential importance of gene-gene interactions
(epistasis), gene-environment interactions, and conditions that break the 'equal
environments' assumption for monozygotic and dizygotic twins. METHOD: A new model
for gene-gene and gene-environment interactions is developed that abandons the
assumptions of the classical twin study, including Fisher's (1918) assumption
that genes act as risk factors for common traits in a manner necessarily
dominated by an additive polygenic term. Provided there are no confounders, the
model can be used to implement a top-down approach to quantifying the potential
utility of genetic prediction and prevention, using twin, family and
environmental data. The results describe a solution space for each disease or
trait, which may or may not include the classical twin study result. Each point
in the solution space corresponds to a different model of genotypic risk and gene
environment interaction. CONCLUSION: The results show that the potential for
reducing the incidence of common diseases using environmental interventions
targeted by genotype may be limited, except in special cases. The model also
confirms that the importance of an individual's genotype in determining their
risk of complex diseases tends to be exaggerated by the classical twin studies
method, owing to the 'equal environments' assumption and the assumption of no
gene-environment interaction. In addition, if phenotypes are genetically robust,
because of epistasis, a largely environmental explanation for shared sibling risk
is plausible, even if the classical heritability is high. The results therefore
highlight the possibility--previously rejected on the basis of twin study results
-that inherited genetic variants are important in determining risk only for the
relatively rare familial forms of diseases such as breast cancer. If so, genetic
models of familial aggregation may be incorrect and the hunt for additional
susceptibility genes could be largely fruitless.
PMID- 17029624
TI - Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced
by heterozygous mutation of Pax6.
AB - BACKGROUND: Knowledge of the consequences of heterozygous mutations of
developmentally important genes is important for understanding human genetic
disorders. The Gli3 gene encodes a zinc finger transcription factor and
homozygous loss-of-function mutations of Gli3 are lethal. Humans heterozygous for
mutations in this gene suffer Greig cephalopolysyndactyly or Pallister-Hall
syndromes, in which limb defects are prominent, and mice heterozygous for similar
mutations have extra digits. Here we examined whether eye development, which is
abnormal in mice lacking functional Gli3, is defective in Gli3+/- mice. RESULTS:
We showed that Gli3 is expressed in the developing eye but that Gli3+/- mice have
only very subtle eye defects. We then generated mice compound heterozygous for
mutations in both Gli3 and Pax6, which encodes another developmentally important
transcription factor known to be crucial for eye development. Pax6+/-; Gli3+/-
eyes were compared to the eyes of wild-type, Pax6+/- or Gli3+/- siblings. They
exhibited a range of abnormalities of the retina, iris, lens and cornea that was
more extensive than in single Gli3+/- or Pax6+/- mutants or than would be
predicted by addition of their phenotypes. CONCLUSION: These findings indicate
that heterozygous mutations of Gli3 can impact on eye development. The importance
of a normal Gli3 gene dosage becomes greater in the absence of a normal Pax6 gene
dosage, suggesting that the two genes co-operate during eye morphogenesis.
PMID- 17029625
TI - Comparative genomics of fungal allergens and epitopes shows widespread
distribution of closely related allergen and epitope orthologues.
AB - BACKGROUND: Allergy is a common debilitating and occasionally life threatening
condition. The fungal kingdom contains a number of species that produce a wide
range of well defined protein allergens although the vast majority of fungal
species have unknown allergenic potential. The recent genome sequencing of a
variety of fungi provides the opportunity to assess the occurrence of allergen
orthologues across the fungal kingdom. Here we use comparative genomics to survey
the occurrence of allergen orthologues in fungi. RESULTS: A database of 82
allergen sequences was compiled and used to search 22 fungal genomes.
Additionally we were able to model allergen structure for representative members
of several highly homologous allergen orthologue classes. We found that some
allergen orthologue classes that had predicted structural congruence to allergens
and allergen epitopes were ubiquitous in all fungi. Other allergen orthologues
classes were less well conserved and may not possess conserved allergen epitope
orthologues in all fungi. A final group of allergen orthologues, including the
major allergens Asp f 1 and Alt a 1, appear to be present in only a limited
number of species. CONCLUSION: These results imply that most fungi may possess
proteins that have potential to be allergens or to cross react with allergens.
This, together with the observation that important allergens such as Asp f 1 are
limited to genera or species, has significant implications for understating
fungal sensitization, and interpreting diagnosis and management of fungal
allergy.
PMID- 17029626
TI - Relating tissue specialization to the differentiation of expression of singleton
and duplicate mouse proteins.
AB - BACKGROUND: Gene duplications have been hypothesized to be a major factor in
enabling the evolution of tissue differentiation. Analyses of the expression
profiles of duplicate genes in mammalian tissues have indicated that, with time,
the expression patterns of duplicate genes diverge and become more tissue
specific. We explored the relationship between duplication events, the time at
which they took place, and both the expression breadth of the duplicated genes
and the cumulative expression breadth of the gene family to which they belong.
RESULTS: We show that only duplicates that arose through post-multicellularity
duplication events show a tendency to become more specifically expressed, whereas
such a tendency is not observed for duplicates that arose in a unicellular
ancestor. Unlike the narrow expression profile of the duplicated genes, the
overall expression of gene families tends to maintain a global expression
pattern. CONCLUSION: The work presented here supports the view suggested by the
subfunctionalization model, namely that expression divergence in different
tissues, following gene duplication, promotes the retention of a gene in the
genome of multicellular species. The global expression profile of the gene
families suggests division of expression between family members, whose expression
becomes specialized. Because specialization of expression is coupled with an
increased rate of sequence divergence, it can facilitate the evolution of new,
tissue-specific functions.
PMID- 17029627
TI - Prognostic factors affecting survival after surgical resection of
gastrointestinal stromal tumours: a two-unit experience over 10 years.
AB - BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common
mesenchymal neoplasm of the gastrointestinal (GI) tract which has only been
recently described based on their specific immunohistochemistry and the presence
of particular KIT-related mutations which potentially make them targets for
tyrosine kinase inhibition. METHODS: Sixty-one patients (29 M; 32 F, median age
60 years; range: 23-86 years) between June 1994 and March 2005, were analyzed
from two allied institutions. Patient, tumour, and treatment variables were
analyzed to identify factors affecting survival. RESULTS: Of the 61 patients, 55
(90%) underwent complete surgical resection of macroscopic disease. The 5-year
overall survival (OS) rate in the 61 patients was 88% and the 5-year disease-free
survival (DFS) in the 55 cases completely resected was 75%. Univariate analysis
revealed that R0 resection was strongly associated with a better OSrate (p <
0.0001). Likewise, univariate analysis also showed high mitotic count of > 10
mitoses/per 50 HPF was a significant variable in worse prognosis for OS ( 10 mitoses/per 50 HPF 74% 5-year OS,
respectively; p = 0.013). On subsequent multivariate analysis, only high mitotic
count remained as a significant negative prognostic variable for OS (p = 0.029).
Among patients resected for cure, there were 8 recurrences during follow-up. The
mean time to recurrence was 21 +/- 10 months (range: 4-36 months). Univariate
analysis revealed that mitotic count of > 10 mitoses per 50 high power fields,
intratumoural necrosis, and pathological tumour size (> 10 cm in maximal
diameter) significantly correlated with DFS (p = 0.006, 0.002 and 0.02,
respectively), with tumour necrosis and high mitotic count remaining as
independent predictive variables affecting prognosis on subsequent multivariate
analysis. CONCLUSION: Most GISTs are resectable with survival principally
dependent upon mitotic count and completeness of resection. Future metabolic and
genetic analyses will define the role of and resistance to induction or
postoperative adjuvant targeted kinase inhibition therapy.
PMID- 17029628
TI - Feedback on the FDA's February 2006 draft guidance on Patient Reported Outcome
(PRO) measures from a developer of PRO measures.
AB - I believe that the FDA guidelines have already had an impact in encouraging good
practice in the use of PROs. There are, however, important improvements that need
to be made to the guidelines, particularly in the use of health status and
quality of life terminology. It is essential to distinguish between health status
and quality of life and to use both terms. Nothing is to be gained and a great
deal will be lost if the term quality of life (which has been misused as an
umbrella term in the past) is abandoned and replaced with the term health status.
Patients want us to consider their quality of life as well as their health. To
abandon the term would be to forget about their quality of life and focus only on
their health. Patients are well able to tell us what quality of life means to
them and to rate the impact of a condition on their quality of life if we use
individualised quality of life measures and individualised condition-specific
quality of life measures to allow them to do so. Although my experience with PRO
measures would support many of the recommendations in the guidelines there are
others that I would not fully agree with or would contradict on the basis of my
own research evidence. I have provided references to that research and hope that
the FDA will feel able to do the same when they finalize their guidelines.
PMID- 17029629
TI - Prognostic significance of fascin expression in advanced colorectal cancer: an
immunohistochemical study of colorectal adenomas and adenocarcinomas.
AB - BACKGROUND: Fascin is an actin bundling protein with roles in the formation of
cell protrusions and motility of mesenchymal and neuronal cells. Fascin is
normally low or absent from epithelia, but is upregulated in several epithelial
neoplasms where it may contribute to an invasive phenotype. Here, we report on
the prevalence and potential clinical significance of fascin expression in
relation to the progression of colorectal adenocarcinoma and to tumor cell
proliferation as measured by Ki67 index. METHODS: Conventional tissue sections of
107 colorectal adenomas and 35 adenocarcinomas were analyzed by
immunohistochemistry for fascin and Ki67 expression. Fascin expression and Ki67
proliferation index were also investigated by use of a tissue microarray
containing cores from a further 158 colorectal adenocarcinomas and 15 adenomas
linked to a CCF, IRB-approved database with a mean of 38 months of clinical
follow-up. Survival analysis was carried out by the Kaplan-Meier and Cox
regression methods. RESULTS: Fascin was not expressed by the normal colonic
epithelium. In conventional sections, 16% of adenomas and 26% of adenocarcinomas
showed fascin expression in greater than 10% of the tumor cells. In the
clinically-annotated tumors, fascin immunoreactivity was more common in tumors
located in the proximal colon (p = 0.009), but was not associated with age,
gender, or TNM stage. Patients with stage III/IV adenocarcinomas (n = 62) with
strong fascin immunoreactivity had a worse prognosis than patients with low or
absent fascin, (3-year overall survival of 11% versus 43% for fascin-negative
patients; p = 0.023). In adenomas, fascin and Ki67 tended to be inversely
correlated at the cellular level; this trend was less apparent in
adenocarcinomas. CONCLUSION: Fascin is upregulated in a proportion of adenomas,
where its expression is often focal. Strong and diffuse expression was seen in a
subset of advanced colorectal adenocarcinomas that correlated with shorter
survival in stage III and IV patients. Fascin may have prognostic value as an
early biomarker for more aggressive colorectal adenocarcinomas.
PMID- 17029630
TI - Microarray analysis after RNA amplification can detect pronounced differences in
gene expression using limma.
AB - BACKGROUND: RNA amplification is necessary for profiling gene expression from
small tissue samples. Previous studies have shown that the T7 based amplification
techniques are reproducible but may distort the true abundance of targets.
However, the consequences of such distortions on the ability to detect biological
variation in expression have not been explored sufficiently to define the true
extent of usability and limitations of such amplification techniques. RESULTS: We
show that expression ratios are occasionally distorted by amplification using the
Affymetrix small sample protocol version 2 due to a disproportional shift in
intensity across biological samples. This occurs when a shift in one sample
cannot be reflected in the other sample because the intensity would lie outside
the dynamic range of the scanner. Interestingly, such distortions most commonly
result in smaller ratios with the consequence of reducing the statistical
significance of the ratios. This becomes more critical for less pronounced ratios
where the evidence for differential expression is not strong. Indeed, statistical
analysis by limma suggests that up to 87% of the genes with the largest and
therefore most significant ratios (p < 10e(-20)) in the unamplified group have a
p-value below 10e(-20) in the amplified group. On the other hand, only 69% of the
more moderate ratios (10e(-20) < p < 10e(-10)) in the unamplified group have a p
value below 10e(-10) in the amplified group. Our analysis also suggests that,
overall, limma shows better overlap of genes found to be significant in the
amplified and unamplified groups than the Z-scores statistics. CONCLUSION: We
conclude that microarray analysis of amplified samples performs best at detecting
differences in gene expression, when these are large and when limma statistics
are used.
PMID- 17029631
TI - Amlodipine versus angiotensin II receptor blocker; control of blood pressure
evaluation trial in diabetics (ADVANCED-J).
AB - BACKGROUND: The coexistence of type 2 diabetes mellitus and hypertension
increases the risk of cardiovascular diseases. The U.K. Prospective Diabetes
Study has shown that blood pressure control as well as blood glucose control is
efficient for prevention of complications in hypertensive patients with diabetes
mellitus. However, some reports have shown that it is difficult to control the
blood pressure and the concomitant use of a plurality of drugs is needed in
hypertensive patients with diabetes mellitus. In recent years renin-angiotensin
system depressants are increasingly used for the blood pressure control in
diabetic patients. Particularly in Japan, angiotensin II (A II) antagonists are
increasingly used. However, there is no definite evidence of the point of which
is efficient for the control, the increase in dose of A II antagonist or the
concomitant use of another drug, in hypertensive patients whose blood pressure
levels are inadequately controlled with A II antagonist. METHODS/DESIGN:
Hypertensive patients of age 20 years or over with type 2 diabetes mellitus who
have been treated by the single use of AII antagonist at usual doses for at least
8 weeks or patients who have been treated by the concomitant use of AII
antagonist and an antihypertensive drug other than calcium channel blockers and
ACE inhibitors at usual doses for at least 8 weeks are included. DISCUSSION: We
designed a multi-center, prospective, randomized, open label, blinded-endpoint
trial, ADVANCED-J, to compare the increases in dose of A II antagonist and the
concomitant use of a Ca-channel blocker (amlodipine) and A II antagonist in
hypertensive patients with diabetes mellitus, whose blood pressure levels were
inadequately controlled with A II antagonist. This study is different from the
usual previous studies in that home blood pressures are assessed as indicators of
evaluation of blood pressure. The ADVANCED-J study may have much influence on
selection of antihypertensive drugs for treatment in hypertensive patients with
diabetes mellitus. It is expected to give an important hint for considering the
validity of selection of antihypertensive drugs from the aspects not only of the
antihypertensive effect but medical cost-effectiveness.
PMID- 17029632
TI - Pituitary tumor-transforming gene expression is a prognostic marker for tumor
recurrence in squamous cell carcinoma of the head and neck.
AB - BACKGROUND: The proto-oncogene pituitary tumor-transforming gene (PTTG) has been
shown to be abundantly overexpressed in a large variety of neoplasms likely
promoting neo-vascularization and tumor invasiveness. In this study, we
investigated a potential role for PTTG mRNA expression as a marker to evaluate
the future clinical outcome of patients diagnosed with primary cancer of the head
and neck. METHODS: Tumor samples derived from primary tumors of 89 patients
suffering from a squamous cell carcinoma were analyzed for PTTG mRNA-expression
and compared to corresponding unaffected tissue. Expression levels were
correlated to standard clinico-pathological parameters based on a five year
observation period. RESULTS: In almost all 89 tumor samples PTTG was found to be
overexpressed (median fold increase: 2.1) when compared to the unaffected tissue
specimens derived from the same patient. The nodal stage correlated with PTTG
transcript levels with significant differences between pN0 (median expression:
1.32) and pN+ (median expression: 2.12; P = 0.016). In patients who developed a
tumor recurrence we detected a significantly higher PTTG expression in primary
tumors (median expression: 2.63) when compared to patients who did not develop a
tumor recurrence (median expression: 1.29; P = 0.009). Since the median
expression of PTTG in patients with tumor stage T1/2N0M0 that received surgery
alone without tumor recurrence was 0.94 versus 3.82 in patients suffering from a
tumor recurrence (P = 0.006), PTTG expression might provide a feasible mean of
predicting tumor recurrence. CONCLUSION: Elevated PTTG transcript levels might be
used as a prognostic biomarker for future clinical outcome (i.e. recurrence) in
primary squamous cell carcinomas of the head and neck, especially in early stages
of tumor development.
PMID- 17029634
TI - Estrogens, selective estrogen receptor modulators, and a selective estrogen
receptor down-regulator inhibit endothelial production of tissue factor pathway
inhibitor 1.
AB - BACKGROUND: Hormone therapy, oral contraceptives, and tamoxifen increase the risk
of thrombotic disease. These compounds also reduce plasma content of tissue
factor pathway inhibitor-1 (TFPI), which is the physiological inhibitor of the
tissue factor pathway of coagulation. The current aim was to study if estrogens
and estrogen receptor (ER) modulators may inhibit TFPI production in cultured
endothelial cells and, if so, identify possible mechanisms involved. METHODS:
Human endothelial cell cultures were treated with 17beta-estradiol (E2), 17alpha
ethinylestradiol (EE2), tamoxifen, raloxifene, or fulvestrant. Protein levels of
TFPI in cell media and cell lysates were measured by an enzyme-linked
immunosorbent assay, and TFPI mRNA levels were assessed by quantitative PCR.
Expression of ERalpha was analysed by immunostaining. RESULTS: All compounds
(each in a concentration of 10 nM) reduced TFPI in cell medium, by 34% (E2), 21%
(EE2), 16% (tamoxifen), and 28% (raloxifene), respectively, with identical
inhibitory effects on cellular TFPI levels. Expression of TFPI mRNA was
principally unchanged. Treatment with fulvestrant, which was also associated with
down-regulation of secreted TFPI (9% with 10 nM and 26% with 1000 nM), abolished
the TFPI-inhibiting effect of raloxifene, but not of the other compounds.
Notably, the combination of 1000 nM fulvestrant and 10 nM raloxifene increased
TFPI secretion, and, conversely, 10 nM of either tamoxifen or raloxifene seemed
to partly (tamoxifen) or fully (raloxifene) counteract the inhibitory effect of
1000 nM fulvestrant. The cells did not express the regular nuclear 66 kDa
ERalpha, but instead a 45 kDa ERalpha, which was not regulated by estrogens or ER
modulators. CONCLUSION: E2, EE2, tamoxifen, raloxifene, and fulvestrant inhibited
endothelial production of TFPI by a mechanism apparently independent of TFPI
transcription.
PMID- 17029633
TI - The evolutionary radiation of Arvicolinae rodents (voles and lemmings): relative
contribution of nuclear and mitochondrial DNA phylogenies.
AB - BACKGROUND: Mitochondrial and nuclear genes have generally been employed for
different purposes in molecular systematics, the former to resolve relationships
within recently evolved groups and the latter to investigate phylogenies at a
deeper level. In the case of rapid and recent evolutionary radiations,
mitochondrial genes like cytochrome b (CYB) are often inefficient for resolving
phylogenetic relationships. One of the best examples is illustrated by
Arvicolinae rodents (Rodentia; Muridae), the most impressive mammalian radiation
of the Northern Hemisphere which produced voles, lemmings and muskrats. Here, we
compare the relative contribution of a nuclear marker--the exon 10 of the growth
hormone receptor (GHR) gene--to the one of the mitochondrial CYB for inferring
phylogenetic relationships among the major lineages of arvicoline rodents.
RESULTS: The analysis of GHR sequences improves the overall resolution of the
Arvicolinae phylogeny. Our results show that the Caucasian long-clawed vole
(Prometheomys schaposnikowi) is one of the basalmost arvicolines, and confirm
that true lemmings (Lemmus) and collared lemmings (Dicrostonyx) are not closely
related as suggested by morphology. Red-backed voles (Myodini) are found as the
sister-group of a clade encompassing water vole (Arvicola), snow vole
(Chionomys), and meadow voles (Microtus and allies). Within the latter, no
support is recovered for the generic recognition of Blanfordimys, Lasiopodomys,
Neodon, and Phaiomys as suggested by morphology. Comparisons of parameter
estimates for branch lengths, base composition, among sites rate heterogeneity,
and GTR relative substitution rates indicate that CYB sequences consistently
exhibit more heterogeneity among codon positions than GHR. By analyzing the
contribution of each codon position to node resolution, we show that the apparent
higher efficiency of GHR is due to their third positions. Although we focus on
speciation events spanning the last 10 million years (Myr), CYB sequences display
highly saturated codon positions contrary to the nuclear exon. Lastly, variable
length bootstrap predicts a significant increase in resolution of arvicoline
phylogeny through the sequencing of nuclear data in an order of magnitude three
to five times greater than the size of GHR exon 10. CONCLUSION: Our survey
provides a first resolved gene tree for Arvicolinae. The comparison of CYB and
GHR phylogenetic efficiency supports recent assertions that nuclear genes are
useful for resolving relationships of recently evolved animals. The superiority
of nuclear exons may reside both in (i) less heterogeneity among sites, and (ii)
the presence of highly informative sites in third codon positions, that evolve
rapidly enough to accumulate synapomorphies, but slow enough to avoid
substitutional saturation.
PMID- 17029636
TI - Error mapping controller: a closed loop neuroprosthesis controlled by artificial
neural networks.
AB - BACKGROUND: The design of an optimal neuroprostheses controller and its clinical
use presents several challenges. First, the physiological system is characterized
by highly inter-subjects varying properties and also by non stationary behaviour
with time, due to conditioning level and fatigue. Secondly, the easiness to use
in routine clinical practice requires experienced operators. Therefore, feedback
controllers, avoiding long setting procedures, are required. METHODS: The error
mapping controller (EMC) here proposed uses artificial neural networks (ANNs)
both for the design of an inverse model and of a feedback controller. A
neuromuscular model is used to validate the performance of the controllers in
simulations. The EMC performance is compared to a Proportional Integral
Derivative (PID) included in an anti wind-up scheme (called PIDAW) and to a
controller with an ANN as inverse model and a PID in the feedback loop
(NEUROPID). In addition tests on the EMC robustness in response to variations of
the Plant parameters and to mechanical disturbances are carried out. RESULTS: The
EMC shows improvements with respect to the other controllers in tracking
accuracy, capability to prolong exercise managing fatigue, robustness to
parameter variations and resistance to mechanical disturbances. CONCLUSION:
Different from the other controllers, the EMC is capable of balancing between
tracking accuracy and mapping of fatigue during the exercise. In this way, it
avoids overstressing muscles and allows a considerable prolongation of the
movement. The collection of the training sets does not require any particular
experimental setting and can be introduced in routine clinical practice.
PMID- 17029635
TI - QualitySNP: a pipeline for detecting single nucleotide polymorphisms and
insertions/deletions in EST data from diploid and polyploid species.
AB - BACKGROUND: Single nucleotide polymorphisms (SNPs) are important tools in
studying complex genetic traits and genome evolution. Computational strategies
for SNP discovery make use of the large number of sequences present in public
databases (in most cases as expressed sequence tags (ESTs)) and are considered to
be faster and more cost-effective than experimental procedures. A major challenge
in computational SNP discovery is distinguishing allelic variation from sequence
variation between paralogous sequences, in addition to recognizing sequencing
errors. For the majority of the public EST sequences, trace or quality files are
lacking which makes detection of reliable SNPs even more difficult because it has
to rely on sequence comparisons only. RESULTS: We have developed a new algorithm
to detect reliable SNPs and insertions/deletions (indels) in EST data, both with
and without quality files. Implemented in a pipeline called QualitySNP, it uses
three filters for the identification of reliable SNPs. Filter 1 screens for all
potential SNPs and identifies variation between or within genotypes. Filter 2 is
the core filter that uses a haplotype-based strategy to detect reliable SNPs.
Clusters with potential paralogs as well as false SNPs caused by sequencing
errors are identified. Filter 3 screens SNPs by calculating a confidence score,
based upon sequence redundancy and quality. Non-synonymous SNPs are subsequently
identified by detecting open reading frames of consensus sequences (contigs) with
SNPs. The pipeline includes a data storage and retrieval system for haplotypes,
SNPs and alignments. QualitySNP's versatility is demonstrated by the
identification of SNPs in EST datasets from potato, chicken and humans.
CONCLUSION: QualitySNP is an efficient tool for SNP detection, storage and
retrieval in diploid as well as polyploid species. It is available for running on
Linux or UNIX systems. The program, test data, and user manual are available at
http://www.bioinformatics.nl/tools/snpweb/ and as Additional files.
PMID- 17029637
TI - PR genes of apple: identification and expression in response to elicitors and
inoculation with Erwinia amylovora.
AB - BACKGROUND: In the past decade, much work has been done to dissect the molecular
basis of the defence signalling pathway in plants known as Systemic Acquired
Resistance (SAR). Most of the work has been carried out in model species such as
Arabidopsis, with little attention paid to woody plants. However within the range
of species examined, components of the pathway seem to be highly conserved. In
this study, we attempted to identify downstream components of the SAR pathway in
apple to serve as markers for its activation. RESULTS: We identified three
pathogenesis related (PR) genes from apple, PR-2, PR-5 and PR-8, which are
induced in response to inoculation with the apple pathogen, Erwinia amylovora,
but they are not induced in young apple shoots by treatment with known elicitors
of SAR in herbaceous plants. We also identified three PR-1-like genes from apple,
PR-1a, PR-1b and PR-1c, based solely on sequence similarity to known PR-1 genes
of model (intensively researched) herbaceous plants. The PR-1-like genes were not
induced in response to inoculation with E. amylovora or by treatment with
elicitors; however, each showed a distinct pattern of expression. CONCLUSION:
Four PR genes from apple were partially characterized. PR-1a, PR-2, PR-5 and PR-8
from apple are not markers for SAR in young apple shoots. Two additional PR-1
like genes were identified through in-silico analysis of apple ESTs deposited in
GenBank. PR-1a, PR-1b and PR-1c are not involved in defence response or SAR in
young apple shoots; this conclusion differs from that reported previously for
young apple seedlings.
PMID- 17029638
TI - Fine motor skills in South African children with symptoms of ADHD: influence of
subtype, gender, age, and hand dominance.
AB - BACKGROUND: Motor problems, often characterised as clumsiness or poor motor
coordination, have been associated with ADHD in addition to the main symptom
groups of inattention, impulsiveness, and overactivity. The problems addressed in
this study were: (1) Are motor problems associated with ADHD symptoms, also in
African cultures? (2) Are there differences in motor skills among the subtypes
with ADHD symptoms? (3) Are there gender differences? (4) Is there an effect of
age? (5) Are there differences in performance between the dominant and non
dominant hand? METHOD: A total of 528 children (264 classified as having symptoms
of ADHD and 264 matched comparisons) of both genders and from seven different
South African ethnic groups participated in the study. They were assessed with
three simple, easy to administer instruments which measure various functions of
motor speed and eye-hand coordination: The Grooved Pegboard, the Maze
Coordination Task, and the Finger Tapping Test. The results were analysed as a
function of subtype, gender, age, and hand dominance. RESULTS: The findings
indicate that children with symptoms of ADHD performed significantly poorer on
the Grooved Pegboard and Motor Coordination Task, but not on the Finger Tapping
Test than their comparisons without ADHD symptoms. The impairment was most severe
for the subtype with symptoms of ADHD-C (combined) and less severe for the
subtypes with symptoms of ADHD-PI (predominantly inattentive) and ADHD-HI
(predominantly hyperactive/impulsive). With few exceptions, both genders were
equally affected while there were only slight differences in performance between
the dominant and non-dominant hand. The deficiencies in motor control were mainly
confined to the younger age group (6-9 yr). CONCLUSION: An association between
the symptoms of ADHD and motor problems was demonstrated in terms of accuracy and
speed in fairly complex tasks, but not in simple motor tests of speed. This
deficiency is found mainly in the children with ADHD-C symptoms, but also to a
lesser degree in the children with symptoms of ADHD-PI and ADHD-HI.
PMID- 17029639
TI - Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial
colorectal cancer predisposition.
AB - BACKGROUND: The observation that germline mutations in the oxidative DNA damage
repair gene MUTYH cause colorectal cancer (CRC) provides strong evidence that
dysregulation of the base excision repair (BER) pathway influences disease
susceptibility. It is conceivable that germline sequence variation in other BER
pathway genes such as NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 also
contribute to CRC susceptibility. METHODS: To evaluate whether sequence variants
of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes might act as CRC
susceptibility alleles, we screened the coding sequence and intron-exon
boundaries of these genes in 94 familial CRC cases in which involvement of known
genes had been excluded. RESULTS: Three novel missense variants were identified
NEIL2 C367A, TDG3 A196G and UNG2 C262T in patients, which were not observed in
188 healthy control DNAs. CONCLUSION: We detected novel germline alterations in
NEIL2, TDG and UNG patients with CRC. The results suggest a limited role for
NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 in development of CRC.
PMID- 17029640
TI - Risk-adjusted cesarean section rates for the assessment of physician performance
in Taiwan: a population-based study.
AB - BACKGROUND: Over the past decade, about one-third of all births nationwide in
Taiwan were delivered by cesarean section (CS). Previous studies in the US and
Europe have documented the need for risk adjustment for fairer comparisons among
providers. In this study, we set out to determine the impact that adjustment for
patient-specific risk factors has on CS among different physicians in Taiwan.
METHODS: There were 172,511 live births which occurred in either hospitals or
obstetrics/gynecology clinics between 1 January and 31 December 2003, and for
whom birth certificate data could be linked with National Health Insurance (NHI)
claims data, available as the sample for this study. Physicians were divided into
four equivalent groups based upon the quartile distribution of their crude
(actual) CS rates. Stepwise logistic regressions were conducted to develop a
predictive model and to determine the expected (risk-adjusted) CS rate and 95%
confidence interval (CI) for each physician. The actual rates were then compared
with the expected CS rates to see the proportion of physicians whose actual rates
were below, within, or above the predicted CI in each quartile. RESULTS: The
proportion of physicians whose CS rates were above the predicted CI increased as
the quartile moved to the higher level. However, more than half of the physicians
whose actual rates were higher than the predicted CI were not in the highest
quartile. Conversely, there were some physicians (40 of 258 physicians) in the
highest quartile who were actually providing obstetric care that was appropriate
to the risk. When a stricter standard was applied to the assessment of physician
performance by excluding physicians in quartile 4 for predicting CS rates, as
many as 60% of physicians were found to have higher CS rates than the predicted
CI, and indeed, the CS rates of no physicians in either quartile 3 or quartile 4
were below the predicted CI. CONCLUSION: Overall, our study found that the
comparison of unadjusted CS rates might not provide a valid reflection of the
quality of obstetric care delivered by physicians, and may ultimately lead to
biased judgments by purchasers. Our study has also shown that when we changed the
standard of quality assessment, the evaluation results also changed.
PMID- 17029641
TI - Scottish survey of diabetes services for minority ethnic groups.
AB - BACKGROUND: In the UK, all ethnic minority groups have higher rates of diabetes
than the general population. Although there have been a number of projects to
assess diabetic care amongst minority ethnic groups in the United Kingdom, little
is known about the extent to which the needs of ethnic minority groups are
actually met by the National Health Service (NHS) Scotland. Therefore we
conducted this study to understand of the current situation for diabetes care
available to minority ethnic groups in Scotland. METHODS: We conducted this cross
sectional study in all health boards in Scotland. A questionnaire was designed
based on expert comments. It was completed by Local Health Care Cooperatives
(LHCC) managers, chairs, diabetes specialist nurses and public health
practitioners. RESULTS: 57 of questionnaires were returned (response rate =
69.5%). Of these LHCCs, 71% responded that diabetes was part of their LHCC plan.
However 69% answered that ethnic group was not recorded by community services and
GPs, and 80% of LHCCs did not monitor trends of complications of diabetes by
ethnic group. CONCLUSION: Improvement is needed in quality, completeness, and
availability of minority ethnic group data for diabetes at a national level,
particularly if NHS Primary Care Organisations are to be responsible for
providing diabetes care as laid out in the Scottish Diabetes Framework.
PMID- 17029642
TI - Design factors that influence PCR amplification success of cross-species primers
among 1147 mammalian primer pairs.
AB - BACKGROUND: Cross-species primers have been used with moderate success to address
a variety of questions concerning genome structure, evolution, and gene function.
However, the factors affecting their success have never been adequately
addressed, particularly with respect to producing a consistent method to achieve
high throughput. Using 1,147 mammalian cross-species primer pairs (1089 not
previously reported), we tested several factors to determine their influence on
the probability that a given target will amplify in a given species under a
single amplification condition. These factors included: number of mismatches
between the two species (the index species) used to identify conserved regions to
which the primers were designed, GC-content of the gene and amplified region, CpG
dinucleotides in the primer region, degree of encoded protein conservation,
length of the primers, and the degree of evolutionary distance between the target
species and the two index species. RESULTS: The amplification success rate for
the cross-species primers was significantly influenced by the number of
mismatches between the two index species (6-8% decrease per mismatch in a primer
pair), the GC-content within the amplified region (for the dog, GC > or = 50%,
56.9% amplified; GC<50%, 74.2% amplified), the degree of protein conservation (R2
= 0.14) and the relatedness of the target species to the index species. For the
dog, 598 products of 930 primer pairs (64.3%) (excluding primers in which dog was
an index species) were sequenced and shown to be the expected product, with an
additional three percent producing the incorrect sequence. When hamster DNA was
used with the single amplification condition in a microtiter plate-based format,
510 of 1087 primer pairs (46.9%) produced amplified products. The primer pairs
are spaced at an average distance of 2.3 Mb in the human genome and may be used
to produce up to several hundred thousand bp of species-specific sequence.
CONCLUSION: The most important factors influencing the proportion of successful
amplifications are the number of index species mismatches, GC-richness of the
target amplimer, and the relatedness of the target species to the index species,
at least under the single PCR condition used. The 1147 cross-species primer pairs
can be used in a high throughput manner to generate data for studies on the
genetics and genomics of non-sequenced mammalian genomes.
PMID- 17029643
TI - Dual use of Medicare and the Veterans Health Administration: are there adverse
health outcomes?
AB - BACKGROUND: Millions of veterans are eligible to use the Veterans Health
Administration (VHA) and Medicare because of their military service and age. This
article examines whether an indirect measure of dual use based on inpatient
services is associated with increased mortality risk. METHODS: Data on 1,566 self
responding men (weighted N = 1,522) from the Survey of Assets and Health Dynamics
among the Oldest Old (AHEAD) were linked to Medicare claims and the National
Death Index. Dual use was indirectly indicated when the self-reported number of
hospital episodes in the 12 months prior to baseline was greater than that
observed in the Medicare claims. The independent association of dual use with
mortality was estimated using proportional hazards regression. RESULTS: 96 (11%)
of the veterans were classified as dual users. 766 men (50.3%) had died by
December 31, 2002, including 64.9% of the dual users and 49.3% of all others, for
an attributable mortality risk of 15.6% (p < .003). Adjusting for demographics,
socioeconomics, comorbidity, hospitalization status, and selection bias at
baseline, as well as subsequent hospitalization for ambulatory care sensitive
conditions, the independent effect of dual use was a 56.1% increased relative
risk of mortality (AHR = 1.561; p = .009). CONCLUSION: An indirect measure of
veterans' dual use of the VHA and Medicare systems, based on inpatient services,
was associated with an increased risk of death. Further examination of dual use,
especially in the outpatient setting, is needed, because dual inpatient and dual
outpatient use may be different phenomena.
PMID- 17029644
TI - An instrument to measure job satisfaction of nursing home administrators.
AB - BACKGROUND: The psychometric properties of the nursing home administrator job
satisfaction questionnaire (NHA-JSQ) are presented, and the steps used to develop
this instrument. METHODS: The NHA-JSQ subscales were developed from pilot survey
activities with 93 administrators, content analysis, and a research panel. The
resulting survey was sent to 1,000 nursing home administrators. Factor analyses
were used to determine the psychometric properties of the instrument. RESULTS: Of
the 1,000 surveys mailed, 721 usable surveys were returned (72 percent response
rate). The factor analyses show that the items were representative of six
underlying factors (i.e., coworkers, work demands, work content, work load, work
skills, and rewards). CONCLUSION: The NHA-JSQ represents a short,
psychometrically sound job satisfaction instrument for use in nursing homes.
PMID- 17029645
TI - A missense mutation in PMEL17 is associated with the Silver coat color in the
horse.
AB - BACKGROUND: The Silver coat color, also called Silver dapple, in the horse is
characterized by dilution of the black pigment in the hair. This phenotype shows
an autosomal dominant inheritance. The effect of the mutation is most visible in
the long hairs of the mane and tail, which are diluted to a mixture of white and
gray hairs. Herein we describe the identification of the responsible gene and a
missense mutation associated with the Silver phenotype. RESULTS: Segregation data
on the Silver locus (Z) were obtained within one half-sib family that consisted
of a heterozygous Silver colored stallion with 34 offspring and their 29 non
Silver dams. We typed 41 genetic markers well spread over the horse genome,
including one single microsatellite marker (TKY284) close to the candidate gene
PMEL17 on horse chromosome 6 (ECA6q23). Significant linkage was found between the
Silver phenotype and TKY284 (theta = 0, z = 9.0). DNA sequencing of PMEL17 in
Silver and non-Silver horses revealed a missense mutation in exon 11 changing the
second amino acid in the cytoplasmic region from arginine to cysteine
(Arg618Cys). This mutation showed complete association with the Silver phenotype
across multiple horse breeds, and was not found among non-Silver horses with one
clear exception; a chestnut colored individual that had several Silver offspring
when mated to different non-Silver stallions also carried the exon 11 mutation.
In total, 64 Silver horses from six breeds and 85 non-Silver horses from 14
breeds were tested for the exon 11 mutation. One additional mutation located in
intron 9, only 759 bases from the missense mutation, also showed complete
association with the Silver phenotype. However, as one could expect to find
several non-causative mutations completely associated with the Silver mutation,
we argue that the missense mutation is more likely to be causative. CONCLUSION:
The present study shows that PMEL17 causes the Silver coat color in the horse and
enable genetic testing for this trait.
PMID- 17029646
TI - Normative data and discriminative properties of short form 36 (SF-36) in Turkish
urban population.
AB - BACKGROUND: SF-36 has been both translated into different languages and adapted
to different cultures to obtain comparable data on health status internationally.
However there have been only a limited number of studies focused on the
discriminative ability of SF-36 regarding social and disease status in developing
countries. The aim of this study was to obtain population norms of the short form
36 (SF-36) health survey and the association of SF-36 domains with demographic
and socioeconomic variables in an urban population in Turkey. METHODS: A cross
sectional study. Face to face interviews were carried out with a sample of
households. The sample was systematically selected from two urban Health
Districts in Izmir, Turkey. The study group consisted of 1,279 people selected
from a study population of 46,290 people aged 18 and over. RESULTS: Internal
consistencies of the scales were high, with the exception of mental health and
vitality. Physical health scales were associated with both age and gender. On the
other hand, mental health scales were less strongly associated with age and
gender. Women reported poorer health compared to men in general. Social risk
factors (employment status, lower education and economic strain) were associated
with worse health profiles. The SF-36 was found to be capable of discriminating
disease status. CONCLUSION: Our findings, cautiously generalisable to urban
population, suggest that the SF-36 can be a valuable tool for studies on health
outcomes in Turkish population. SF-36 may also be a promising measure for
research on health inequalities in Turkey and other developing countries.
PMID- 17029649
TI - Biological imaging using secondary ions.
AB - Biological materials are morphologically and chemically complex. A quantitative
imaging tool is now available that can produce chemical, and even metabolic,
information from morphological features as small as a few nanometers.
PMID- 17029648
TI - HIV prevalence and factors associated with HIV infection among male injection
drug users under 30: a cross-sectional study in Long An, Vietnam.
AB - BACKGROUND: Sufficient targeted HIV prevention activities aiming at reducing HIV
transmission within and from an extremely marginalized population of injection
drug users (IDUs) must urgently and efficiently be implemented in Vietnam. This
study was conducted to facilitate the development of such activities by
describing transmission risks of young IDUs and evaluating factors in association
with HIV infection. METHODS: Thirty clusters were selected from 29 hotspot
communes in Long An province by probability proportional to size (PPS) sampling
method. The snowball technique was used for enrolling participants in each
cluster. The cross-sectional association of factors obtained during direct
structured interviews to 248 male IDUs aged 14 to 29 years old and with their HIV
test results were examined. RESULTS: The HIV prevalence among the studied IDUs
was 32%. Age range of 18-20 years old, low educational level, sharing injection
equipment or injection drug use in the other cities were independently associated
with HIV serostatus in the multivariate analysis. Sexual behaviors did not differ
between HIV-positive and -negative IDUs. Among HIV seropositive IDUs who had
sexual contact with primary (n = 37), casual (n = 6), and commercial (n = 15)
partners, only 5.4% (n = 2), 33.3% (n = 2), and 46.7% (n = 7), respectively,
responded that they had used condoms every time. CONCLUSION: About one-third of
young IDUs aged less than 30 identified in the hotspot communes in Long An,
Vietnam was found to be infected with HIV, and socio-demographic and injection
related factors might account for the infection risk. Prevailing risky sexual
behavior of this extremely marginalized population highlights the need to reduce
their high transmission risks as a public health priority.
PMID- 17029651
TI - Recently published papers: pneumonia, hypothermia and the elderly.
AB - Pneumonia (hospital-acquired and community-acquired) is commonly encountered in
intensive care. Several papers recently published on this subject have shed more
light on different aspects of this important topic. Hypothermia has been shown to
improve post-arrest outcome, but how often do we use it? And finally, several
papers have recently appeared in the journals related to the admission of the
elderly to the critical care area and their outcome.
PMID- 17029652
TI - Drotrecogin alfa (activated): down and not out, but not really in either.
PMID- 17029653
TI - Evidence-based medicine: classifying the evidence from clinical trials--the need
to consider other dimensions.
AB - The current approach to assessing the quality of evidence obtained from clinical
trials focuses on three dimensions: the quality of the design (with double
blinded randomised controlled trials representing the highest level of such
design); the statistical power (beta) and the level of significance (alpha).
While these aspects are important, we argue that other significant aspects of
trial quality impinge upon the truthfulness of the findings: biological
plausibility, reproducibility and generalisability. We present several recent
studies in critical care medicine where the design, beta and alpha components of
the study are seemingly satisfactory but where the aspects of biological
plausibility, reproducibility and generalisability show serious limitations.
Accordingly, we argue for more reflection, definition and consensus on these
aspects of the evaluation of evidence.
PMID- 17029647
TI - Human malarial disease: a consequence of inflammatory cytokine release.
AB - Malaria causes an acute systemic human disease that bears many similarities, both
clinically and mechanistically, to those caused by bacteria, rickettsia, and
viruses. Over the past few decades, a literature has emerged that argues for most
of the pathology seen in all of these infectious diseases being explained by
activation of the inflammatory system, with the balance between the pro and anti
inflammatory cytokines being tipped towards the onset of systemic inflammation.
Although not often expressed in energy terms, there is, when reduced to
biochemical essentials, wide agreement that infection with falciparum malaria is
often fatal because mitochondria are unable to generate enough ATP to maintain
normal cellular function. Most, however, would contend that this largely occurs
because sequestered parasitized red cells prevent sufficient oxygen getting to
where it is needed. This review considers the evidence that an equally or more
important way ATP deficiency arises in malaria, as well as these other infectious
diseases, is an inability of mitochondria, through the effects of inflammatory
cytokines on their function, to utilise available oxygen. This activity of these
cytokines, plus their capacity to control the pathways through which oxygen
supply to mitochondria are restricted (particularly through directing
sequestration and driving anaemia), combine to make falciparum malaria primarily
an inflammatory cytokine-driven disease.
PMID- 17029654
TI - Combined functional task practice and dynamic high intensity resistance training
promotes recovery of upper-extremity motor function in post-stroke hemiparesis: a
case study.
AB - BACKGROUND AND PURPOSE: Weakness is a significant impairment in persons with post
stroke hemiparesis, yet traditional clinical perspectives caution against
strengthening in neurological populations. Significant correlations between
weakness and functional movement have been demonstrated, however, a clear
relationship between increased strength and functional improvement has been
elusive. This case study describes a combined program of dynamic, high-intensity
resistance training and functional task practice for the upper-extremity in adult
hemiparesis. CASE DESCRIPTION: The patient was a 65-year-old, right hand dominant
woman who presented to the Neural Control of Movement Laboratory at the Palo Alto
VA Rehabilitation Research and Development Center 16 weeks following clipping of
an unruptured aneurysm with consequent dense right hemiparesis. She received 7
weeks of acute rehabilitation according to CARF guidelines (ie, at least 3 hours
of two or more disciplines, 6 days per week). Her baseline research evaluation
revealed significant upperextremity deficits at the ICF body structure/function
level including: weakness, shoulder pain, mild resistance to passive movement,
and need for moderate to maximal assistance in many activities of daily living
including bathing and dressing. The Stroke Impact Scale score reporting her
perspective indicated she had recovered from her stroke only 50%. The hybrid
resistance training-functional task practice intervention, detailed in this
report, was delivered 3 times per week for 6 weeks with each session lasting
75:00. OUTCOMES: The subject revealed marked improvements in isometric and
dynamic force production in 5 key upper-extremity actions: elbow flexion, elbow
extension, shoulder flexion, shoulder abduction, and shoulder external rotation.
Strength gains were accompanied by increased EMG activation immediately
postintervention and by a combination of increased activation and apparent
hypertrophic effects at 6 month follow up. Marked improvements were noted in all
clinical and functional measures and in an elbow trajectorytracking task which
served as a surrogate measure of motor control. DISCUSSION: Improvements in
strength and positive outcome effects at the physiological, clinical, and
functional levels were observed in this subject following the experimental hybrid
upper-extremity rehabilitation intervention described. Importantly, no
deleterious effects were observed including exacerbation of spasticity or
musculoskeletal compromise. Observations of improved EMG activation in this case
study suggest that improvements in motor activation underlie these strength gains
and can likely be attributed to working at a high intensity level.
PMID- 17029655
TI - Optimal movement variability: a new theoretical perspective for neurologic
physical therapy.
AB - Variability is a natural and important feature of human movement. Using existing
theoretical frameworks as a foundation, we propose a new model to explain
movement variability as it relates to motor learning and health. We contend that
mature motor skills and healthy states are associated with an optimal amount of
movement variability. This variability also has form and is characterized by a
chaotic structure. Less than optimal movement variability characterizes
biological systems that are overly rigid and unchanging, whereas greater than
optimal variability characterizes systems that are noisy and unstable. Both
situations characterize systems that are less adaptable to perturbations, such as
those associated with abnormal motor development or unhealthy states. From our
perspective, the goal of neurologic physical therapy should be to foster the
development of this optimal amount of movement variability by incorporating a
rich repertoire of movement strategies. The development of such a repertoire can
be enhanced by incorporating a multitude of experiences within the therapeutic
milieu. Promoting complex variation in human movement allows either motor
development or the recovery of function after injury not to be hard coded, but
determined instead by the active engagement of the individual within their
environment. Measurement tools derived from nonlinear dynamics that characterize
the complexity of movement variability provide useful means of testing these
propositions. To illustrate, we present 2 clinical case studies, one pediatric
and one adult, where we applied our theoretical framework to measuring change in
postural control.
PMID- 17029656
TI - Combined task-specific training and strengthening effects on locomotor recovery
post-stroke: a case study.
AB - BACKGROUND AND PURPOSE: Task-specific and strength training have demonstrated
efficacy as therapeutic interventions poststroke. The intent of this case study
is to describe outcomes associated with a therapy program that combines task
specific and strength training in an individual post-stroke and to discuss some
possible mechanisms and modulating factors that may affect post-stroke neurologic
recovery and responsiveness to intervention. CASE DESCRIPTION: The participant
was a 38-year-old female with right middle cerebral artery stroke, evaluated 15
months postonset. She ambulated independently with an ankle-foot orthosis and
straight cane. Her free and fast overground velocity was 0.50 m/s and 0.62 m/s,
respectively. Body-weight supported treadmill training and a limb-loaded cycling
exercise were alternated over 24 treatments sessions (4 times/wk for 6 wks).
Measurements were taken pre-, post-treatment, and at a 6-mo follow-up.
Instrumented gait and motion analysis with fine-wire EMG recording of LE muscle
activity occurred pre- and post-treatment. OUTCOMES: Post-treatment, walking
speed increased 18% for free--(0.59 m/ s) and 14.4% for fast-velocity (0.71 m/s);
6-min walking distance increased 4% (184.4 m). At 6-mos, continued improvements
in all walking outcomes were evident. Gait and motion analysis revealed that
functional locomotor recovery was associated with increases in magnitude of
paretic leg gluteus maximus and gluteus medius activation during gait. Motion
analysis confirmed an increase of hip and knee extension motions throughout
stance and swing. DISCUSSION: For the person in this case clinically meaningful
changes in walking function were associated with a combined therapeutic program
that included both task-specific and LE strength training. Possible mechanisms
associated with response to therapy were related to improved motor unit
activation associated with increased strength in key muscles used in gait.
PMID- 17029657
TI - A perception-action framework for physical therapy for persons with neurologic
dysfunction: use of therapeutic affordance and unitless ratio.
AB - BACKGROUND AND PURPOSE: Our goal through this case study is to introduce the
reader to the perception-action framework (PAF) for human action and the
application of this framework to examination and treatment in physical therapy.
We define the concepts of affordance, constraints, and emergent action as example
concepts in the PAF and then apply these concepts to examination and treatment in
physical therapy through the use of unitless ratios. At critical values of these
ratios, the coordination pattern used or the action taken undergoes a shift. We
offer examples that contrast some of the unique aspects of the PAF to approaches
such as the hierarchical or motor program approaches that primarily focus on the
nervous system influence on the motor aspects of human action. CASE DESCRIPTION:
This principled approach to examination and treatment can be used with patients
of all ages. Here, we provide the case of a 59-year-old, right handed male status
post acute, embolic stroke with right posterior cerebral artery (PCA) and right
middle cerebral artery (MCA) territory infarcts. The PAF and the specific use of
unitless ratios for examination and treatment of reaching and grasping are
detailed. OUTCOMES: Research supports that the unitless ratio created from the
size of a cube to the range of motion of the index finger-thumb aperture defines
the boundaries for the shift between a 1 handed and a 2 handed reach regardless
of age. These boundary conditions are used to examine the subjects grasping
abilities and the emergent reaching coordination pattern that occurs as cube size
is varied. SUMMARY: Therapeutic use of the PAF requires new examination and
intervention strategies predicated on the development of unitless ratios for
functional human actions. Key Words: perception-action; stroke, motor control,
unitless ratio.
PMID- 17029658
TI - Attempting to improve function and quality of life using the FTM Protocol: case
report.
AB - BACKGROUND AND PURPOSE: The Functional Tone Management (FTM) arm training program
uses repetitive task practice, stretching, and electrical stimulation as patients
with moderate upper extremity hemiparesis wear a dynamic hand orthosis to retrain
grasp and release of objects. The case study quantitatively evaluates the extent
to which FTM training improved function and quality of life in a patient who met
criteria for which the device was intended. CASE DESCRIPTION: The participant, a
44-year-old male in the chronic stage of stroke recovery with moderate right
upper extremity motor impairment, was trained for 10 days over a 2-week period by
a licensed clinician with extensive experience in FTM training methods.
Measurements were taken over 3 baseline visits, then immediately preintervention,
postintervention, and at a 3-month follow-up. The outcome measures, following the
International Classification of Functioning, Disability, and Health (ICF) Model,
included the: Fugl-Meyer assessment (FMA) (upper extremity portion), UE range of
motion (ROM), Modified Ashworth scale, Wolf Motor Function Test (WMFT), and the
Motor Activity Log (MAL). Health related quality of life was measured using the
Stroke Impact Scale (SIS). OUTCOMES: The participant showed limited gains in
upper extremity function immediately postintervention. Increases in AROM occurred
in forearm supination and wrist flexion and extension, but no improvements were
noted in finger ROM. A slight decrease in tone was found in forearm pronators (1
to 0) and wrist flexors (1+ to 1). WMFT values for the more affected upper
extremity did not change immediately after training, but a 17% reduction in time
occurred at follow-up, with improvements, most notably in the tasks of lifting a
pencil and lifting a paper clip. No changes occurred in UE-FMA scores immediately
following the intervention, however, a 17% improvement was measured at followup.
A slight improvement in MAL scores was noted but not to a level of independent
functional use of the impaired upper extremity. SIS scores improved in the
domains of strength, communication, mobility, social participation, hand
recovery, and overall physical component, while decreases were seen in the
ADL/IADL, hand function, emotion, and cognitive domains. DISCUSSION: The case
study indicates that for this patient with chronic, moderate upper extremity
impairment following stroke, a 2-week FTM training regimen resulted in modest
changes occurring as a decrease in impairment, with functional improvement and
improved quality of life. Further investigation of the innovative training
program should be undertaken before the efficacy of its use can be ascertained
amongst patients with limitations comparable to the participant.
PMID- 17029659
TI - Perspective: impact of the IIISTEP conference on clinical practice.
AB - In July 2005, physical therapy clinicians, educators, and researchers gathered
for the IIISTEP (Symposium on Translating Evidence to Practice) conference. The
purpose of IIISTEP was to link research and clinical practice through the
exchange of ideas and research findings between scientists and clinicians. This
paper represents the personal perspective of a group of colleagues who attended
IIISTEP as clinicians/educator teams. The purpose of this paper is to illustrate
how information from IIISTEP has challenged our existing concepts regarding
physical therapy practice and begun to alter our clinical practice. Some key
concepts presented by scientists and clinicians at IIISTEP are reviewed including
current perspectives on neuroplasticity and frameworks for considering function,
health, and the disablement process. Considerations for clinical application are
outlined. Patient cases are used to illustrate how integration of this
information has altered our approach to patient management.
PMID- 17029660
TI - Biosocial and nutritional effects on body composition in young adults from
Wroclaw, Poland.
AB - This work concerns the questions if and to what extent social variables past and
present, and actual sports activity and nutritional and smoking habits, have an
influence on body compartment indices, and how this differs between female and
male medical students from Wroclaw, Poland. Backward stepwise regression was
applied to four dependent variables, i.e. Body Mass Index (BMI), %Fat Mass (%FM),
Extracellular Water/Intracellular Water Index (100 x ECW/ICW) and Body Cell Mass
Index (BCMI=BCM/height2), and for eighteen independent variables including
nutrition, parents' social status, smoking and sports activity. Females ate meat
less frequently and fruit and vegetables more often, and drank beer less
frequently but milk more often than did male students. It seems that there exists
some effect on fat accumulation resulting from difference in nutrition between
females and males. The results may be interpreted in terms of a parental gender
effect on body composition of children associated with different conditions of
life and nutrition in childhood and youth for female and male students in
Wroclaw.
PMID- 17029661
TI - It's all in the timing: coital frequency and fertility awareness-based methods of
family planning.
AB - Fertility awareness-based methods of family planning help women to identify the
days of the cycle they should avoid unprotected intercourse to prevent pregnancy.
Therefore using fertility awareness-based methods influences the timing of sexual
activity, which may affect the nature of the sexual relationship. Data are used
from the clinical trials of two fertility awareness-based methods--the Standard
Days Method and the TwoDay Method--to determine the frequency and timing of
intercourse during the cycle, and the determinants of coital frequency. The mean
coital frequency of study participants was similar to that reported by users of
other methods. Results suggest that coital frequency increases with consecutive
cycles of method use. At the same time the frequency of intercourse during the
identified fertile days and during menses decreases. This evidence implies a
behavioural change as couples get more experience using their method and
communicating about the fertile days. Coital frequency was also influenced by the
method used and by the study sites. Potential differences between the methods and
sites that may contribute to this effect are discussed.
PMID- 17029662
TI - Disagreement in spousal reports of current contraceptive use in sub-Saharan
Africa.
AB - Contraceptive prevalence is a key variable estimated from Demographic and Health
Surveys. But the prevalence estimated from reports of husbands differs widely
from that estimated for wives. In this research, using data from six Demographic
and Health Surveys of sub-Saharan Africa, reports from spouses in monogamous
couples with no other reported sex partners in the recent period are examined.
Agreement ranged from 47% to 82%, but among couples in which one or both reported
use, the 'both' category represented less than half in all nations except
Zimbabwe. Husbands generally had higher reports of condoms, periodic abstinence
and pills but fewer reports of the IUD, injections and female sterilization.
Either discussion of family planning with the spouse and/or higher socioeconomic
status was associated with agreement in most of the surveys. Ambiguities in the
survey question regarding current use need to be reduced, perhaps with an added
probe question for non-permanent methods.
PMID- 17029663
TI - Age dependent increase in early resistance of mice to Mycobacterium tuberculosis
is associated with an increase in CD8 T cells that are capable of antigen
independent IFN-gamma production.
AB - The lungs of naive 18-month-old mice contain an abundant resident population of
CD8 T cells that express typical markers of memory, express elevated levels of
Th1 cytokine receptors on their surface, and are capable of non-specific IFN
gamma production in response to a Th1 cytokine cocktail. In this study we
characterize this population of CD8 T cells in the lungs and spleens of mice with
increasing age. In general, the proportion of CD8 T cells expressing markers of
memory and Th1 cytokine receptors increased with age. The enhanced ability of CD8
T cells to produce IFN-gamma in an antigen independent manner followed this
pattern as well, beginning to increase between 6 and 12 months of age.
Interestingly, the phenotypic and functional age-related changes in CD8 T cells
were also associated with a progressive age-related increase in early resistance
to Mycobacterium tuberculosis. Taken together, these data suggest that as mice
age a population of memory CD8 T cells, that are capable of contributing to
innate immune responses to M. tuberculosis, gradually emerges and could be
relevant for developing strategies to enhance immunity in the elderly.
PMID- 17029664
TI - Effect of age on skeletal muscle myofibrillar mRNA abundance: relationship to
myosin heavy chain protein synthesis rate.
AB - Age-related changes in myosin heavy chain (MHC) phenotype impact both the
quantity and functional character of skeletal muscle. The present study was
undertaken to examine the hypothesis that age-related changes in MHC mRNA
abundance underlie alterations in protein synthesis rates and content. We
measured the abundance of mRNA for MHC isoforms (MHC I, MHC IIa, IIx) and actin
by RT-PCR in 6 young (mean +/- SE; 29 +/- 3) and 12 elderly (73 +/- 1 yr; P<0.01)
volunteers and examined their association to MHC protein synthesis rates and
their respective protein products. We found no differences between young and
elderly volunteers in MHC isoform or actin transcript levels. Because of the
absence of age effects, data were pooled for correlation analyses. Although total
MHC mRNA levels were not related to MHC fractional synthesis rates, the relative
abundance of MHC I and MHC IIa mRNA were positively (r = 0.450; P = 0.06) and
negatively (r = -0.493; P<0.05) associated with MHC protein synthesis rates,
respectively. MHC mRNA levels were positively correlated to their respective
protein products (range of r-values: 0.551-0.727; P<0.05 to P<0.01), but were not
related to skeletal muscle IGF-I mRNA abundance, circulating IGF-I or markers of
immune activation. Our results argue against the notion that changes in MHC
protein synthesis rates with age are related to altered MHC mRNA abundance,
although our findings do suggest that possibility that individual variability in
MHC protein synthesis rates is related to the relative abundance of MHC I versus
MHC IIa transcripts.
PMID- 17029665
TI - Elevated caspase and AIF gene expression correlate with progression of sarcopenia
during aging in male F344BN rats.
AB - To establish the relationship between the progression of sarcopenia and apoptosis
we examined apoptotic gene expression in plantaris muscles (Pl) from 8 mo old
(n=8), 30 mo old (n=8) and 35 mo old (n=6) male rats by real-time PCR. Pl mass
declined from 368 +/- 7 mg at 8 mo to 333 +/- 7 mg at 30 mo (P<0.05) and 210 +/-
15 mg at 35 mo of age (P<0.05). BAX, Bcl-2, and Apaf-1 expression decreased by 62
74% at 30 mo and by 90-96% at 35 mo of age (all P<0.05 vs 8 mo old). In contrast,
the expression of Caspases 3, 8, and 9 and AIF increased 3- to 5-fold at 30 mo
(NS) and 7- to 50-fold at 35 mo of age (P<0.05). There were significant (P<0.05)
correlations between Pl mass and Caspase 3 (r(2)=-0.60), Caspase 9 (r(2)=-0.58),
Caspase 8 (r(2)=-0.50), and AIF (r(2)=-0.48). Thus, our results show that the
expression of some genes involved in apoptosis increase with aging in Pl and
correlate with progression of sarcopenia (Caspase 3, Caspase 9, Caspase 8, and
AIF), whereas others decline with aging (BAX, Bcl-2, and Apaf-1).
PMID- 17029666
TI - Radionuclides in marine macroalgae from Amchitka and Kiska Islands in the
Aleutians: establishing a baseline for future biomonitoring.
AB - Levels of radionuclides in seven species of marine brown algae and Ulva were
determined to establish a baseline for the Northern Pacific Ocean/Bering Sea
(Aleutian Islands). There were differences in levels among algal species and
locations (Amchitka Island vs Kiska Island). No values were above the minimum
detectable activity (MDA) level for (137)Cs, (129)I, (60)Co, (152)Eu, (90)Sr, and
(99)Tc. There were interspecific differences in some radionuclides: Ulva lactuca
(=Ulva fenestrata) had the highest levels of (241)Am, Alaria fistulosa had the
highest levels of (239,240)Pu, and Fucus distichus (=Fucus gardneri) had the
highest levels of (234)U, (235)U, and (238)U. However, levels of all
radionuclides were generally low and near the MDA for all isotopes. Although
Amchitka Island had higher levels of (239,240)Pu than Kiska, the differences were
very small and not significant biologically. The data indicate that algae can be
useful bioindicators of actinides because they accumulate them at very low
environmental levels, allowing them to provide early warning of any potential
seepage of radionuclides into the marine environment. Further, the data indicate
that some species (the intertidal Fucus) are better accumulators than others, and
these should be used as bioindicators in future monitoring schemes.
PMID- 17029667
TI - Speciation of 210Po and 210Pb in air particulates determined by sequential
extraction.
AB - Speciation of (210)Po and (210)Pb in air particulates of two Syrian phosphate
sites with different climate conditions has been studied. The sites are the mines
and Tartous port at the Mediterranean Sea. Air filters were collected during
September 2000 until February 2002 and extracted chemically using different
selective fluids in an attempt to identify the different forms of these two
radionuclides. The results have shown that the inorganic and insoluble (210)Po
and (210)Pb (attached to silica and soluble in mineral acids) portion was found
to be high in both sites and reached a maximum value of 94% and 77% in the mine
site and Tartous port site, respectively. In addition, only 24% of (210)Pb in air
particulates was found to be associated with organic materials probably produced
from the incomplete burning of fuel vehicle and similar activities. Moreover, the
(210)Po/(210)Pb activity ratio in air particulates was higher than that in all
samples at both sites and varied between 3.85 in November 2000 at Tartous port
site and 20 in April 2001 at the mine area. These activity ratios were also
higher than the natural levels. The (210)Po/(210)Pb activity ratio was also
determined in each portion resulting from the selective extraction and found to
be higher than that in most samples. The sources of (210)Po excess in these
portions are discussed. Soil suspension, which is common in the dry climate
dominant in the area, sea water spray and heating of phosphate ores were
considered; polonium is more volatile than the lead compounds at even moderate
temperature. Furthermore, variations in the chemical forms of (210)Po and (210)Pb
during the year were also investigated. However, the results of this study can
also be utilized for dose assessment to phosphate industry workers.
PMID- 17029668
TI - Evaluation of paclitaxel rearrangement involving opening of the oxetane ring and
migration of acetyl and benzoyl groups.
AB - The stability of drug is a critical factor in quality control, drug efficacy,
safety, storage, and production conditions. The rearrangement of paclitaxel,
which involves opening of the oxetane ring and migration of acetyl group occurred
on heating a powder of purified paclitaxel. Subsequently, the unusual migration
of benzoyl groups progressed rapidly in organic solvents. These rearrangement
derivatives were isolated carefully. The structures of the intermediate
derivative A and the product derivative B were confirmed using (1)H NMR, high
performance liquid chromatography (HPLC), and mass spectrometry. We proposed the
rearrangement pathway here for the first time. Neither derivative exhibited
bioactivity in SKOV3 (ovarian cancer) or MDA-MB-435 (breast cancer) cell culture
assays.
PMID- 17029669
TI - Rapid determination of total solanesol in tobacco leaf by ultrasound-assisted
extraction with RP-HPLC and ESI-TOF/MS.
AB - A reliable and rapid method based on high-performance liquid chromatography (HPLC
UV) and positive ion electrospray-time of flight mass spectrometry (ESI-TOF/MS)
has been developed for the characterization and quantification of solanesol in
extracts of tobacco leaves from different sources. The solanesol was extracted
from tobacco leaf via saponification and ultrasonic-assist extraction, and the
extraction conditions were optimized. The HPLC conditions are as following:
Hypersil C(4) (4.6 mm x 150 mm, 5 microm) column, acetonitrile and water as
mobile phase, flow-rate is 0.8 ml/min, detection length of UV is 202 nm,
injection volume is 10 microl. The results indicated that the developed HPLC
method is simple, sensitive and reliable for the determination of solanesol in
tobacco leaves with a linear dynamic range of 3.65-4672 ng, a detection limit of
1.83 ng, and an average recovery of 98.7%. The method has been applied to analyze
and compare different tobacco samples. The results show that the solanesol
content in samples of different geographic locations varies widely from 0.20 to
1.50%. When different parts of the tobacco plant are compared, the top parts of
the leaves are more abundant in solanesol content than those of lower parts.
PMID- 17029670
TI - LC-MS/MS method for simultaneous determination of viramidine and ribavirin levels
in monkey red blood cells.
AB - A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS)
method has been developed for the simultaneous determinations of total viramidine
(viramidine, viramidine monophosphate, viramidine diphosphate, and viramidine
triphosphate) and total ribavirin (ribavirin, ribavirin monophosphate, ribavirin
diphosphate, and ribavirin triphosphate) in monkey red blood cells (RBC). The
method involves the addition of internal standards and perchloric acid,
conversion of viramidine or ribavirin phosphorylated metabolites to viramidine or
ribavirin, purification with an aminopropyl (NH(2)) solid phase extraction (SPE)
cartridge, and LC-MS/MS analysis. The MS/MS is selected to monitor m/z 245-->113,
250-->113, 244-->112, and 249-->112 for ribavirin, [(13)C]ribavirin, viramidine,
and [(13)C]viramidine, respectively, using positive electrospray ionization. The
calibration curves are linear over a concentration range of 100-10,000 ng/mL
(0.412-41.2 microM) with a lower limit of quantification (LLOQ) of 100 ng/mL for
both compounds. Mean inter-assay recoveries for ribavirin are 101%, 98.9%, and
96.0%, with coefficient of variance (%CV) values between 1.95 and 4.50% for 100,
1000, and 10,000 ng/mL quality control (QC) samples, respectively. Mean inter
assay recoveries for viramidine are 96.3%, 101%, and 102%, with coefficient of
variation (%CV) values between 3.61 and 7.22%, for 100, 1000, and 10,000 ng/mL QC
samples, respectively. Over-curve dilution QC at 400 microg/mL (1639 microM) for
both viramidine and ribavirin are used to ensure the dilution accuracy (25 X
dilutions) for monkey samples. The method has been used to simultaneously
determine the total concentrations of ribavirin and viramidine in monkey RBC
following 5, 15, and 36 weeks dosing of viramidine or ribavirin (60 mg/kg). The
concentrations of total ribavirin following ribavirin dosing are 1242 microM at
week 5, 1257 microM at week 15, and 1146 microM at week 36. The concentrations of
total ribavirin following viramidine dosing are 634 microM at week 5, 716 microM
at week 15, and 683 microM at week 36. Only small amounts of viramidine are
detected in RBC following viramidine dosing, 7.80 microM at week 5, 6.63 microM
at week 15, and 10.4 microM at week 36. The results suggest that ribavirin levels
in RBC were at steady state at week 5 of ribavirin or viramidine dosing. At
steady state, ribavirin levels in RBC are approximately 2x after ribavirin dosing
than viramidine dosing. The relatively small percentage of viramidine in RBC
suggests that viramidine either poorly penetrated into RBC or was extensively
converted to ribavirin following entry into RBC.
PMID- 17029671
TI - Metabolomic discrimination of different grades of pine-mushroom (Tricholoma
matsutake Sing.) using 1H NMR spectrometry and multivariate data analysis.
AB - Metabolomic analysis of raw and cooked pine-mushrooms (Tricholoma matsutake
Sing.) of different grades was performed using (1)H nuclear magnetic resonance
(NMR) spectrometry and principal component analysis (PCA). PCA of the (1)H NMR
spectra of aqueous fractions allowed different grades of raw pine-mushroom to be
discriminated by a combination of principal component (PC) 1 and PC 2, which
accounted cumulatively for 94.1% of the variation in all variables. The major
peaks in the (1)H NMR spectra that contributed to discrimination of raw mushrooms
were assigned to choline, trehalose, threonine, leucine/isoleucine, succinic
acid, alanine, and fumaric acid. The combination of PC 1 (70.8%) and PC 3 (7.5%)
allowed different grades of cooked pine-mushroom to be discriminated, and the
major peaks in the (1)H NMR spectra that contributed to discrimination of cooked
mushrooms were assigned to succinic acid, trehalose, and fumaric acid. This
metabolomic analysis-based method allows different grades of pine-mushroom to be
distinguished without any prepurification.
PMID- 17029672
TI - Analysis of dencichine in Panax notoginseng by gas chromatography-mass
spectrometry with ethyl chloroformate derivatization.
AB - Dencichine (beta-N-oxalyl-l-alpha,beta-diaminopropionic acid) is a haemostatic
agent present in well-known traditional Chinese medicinal herbs such as Panax
notoginseng, as well as other Panax species. It is also a reported neurotoxic
agent found in Lathyrus sativus (grass pea seed) and cycad seeds. A method was
developed for quantitative determination of the non-protein amino acid,
dencichine, in plant samples of P. notoginseng and the adventitious roots
directly from the explants of P. notoginseng after derivatization with ethyl
chloroformate (ECF) by gas chromatography-mass spectrometry (GC-MS). l-2
chlorophenylalanine was used as an internal standard. Calibration curves were
linear (r(2)=0.9988, n=6) in the range of 10-800 microg/ml for dencichine. Limit
of detection and quantification for dencichine were 0.5 microg/ml and 2
microg/ml, respectively. This rapid and specific method may be applied to the
quantification of dencichine in complex medicinal plants and their products.
PMID- 17029673
TI - Sagittal curvature of total knee replacements predicts in vivo kinematics.
AB - BACKGROUND: It is known that in vivo kinematics after total knee replacement is
influenced by the design of the implant. The goal of this study was to show that
the sagittal curvature of two different knee prostheses differing in geometric
design predicts their in vivo motion behavior. METHODS: Three-dimensional tibio
femoral displacements of two prosthesis designs (single radius vs. dual radius)
were measured during knee extension under weight bearing conditions by in vivo
video fluoroscopy. Finite helical axes were computed to represent the tibio
femoral motions. Angular deviation alpha and the spatial localization deviation
delta were used to characterize the motions. Angular deviation is the angle
between each incremental finite helical axis and the medio-lateral axis of the
femoral component of the prosthesis. The spatial localization deviation is the
distance between each finite helical axis and the center of the femoral component
of the prosthesis. Statistical comparisons were performed using the median and
the interquartile range of the angular deviation and the spatial localization
deviation. FINDINGS: The single-radius design showed finite helical axes
concentrated at a single axis near to the medio-lateral axis of the femoral
component. The angular and spatial localization deviation of the dual radius
design were larger compared to the single radius design, exhibiting finite
helical axes varying between two axes. INTERPRETATION: Video fluoroscopy in
combination with finite helical axis analysis proved to be suitable methods to
evaluate the in vivo kinematical behavior of total knee arthroplasty, which can
be useful for implant designers. Knowledge of in vivo kinematics can also provide
surgeons with more background information about the total knee arthroplasty
models they implant.
PMID- 17029674
TI - Refeeding and insulin activate the AKT/p70S6 kinase pathway without affecting
IRS1 tyrosine phosphorylation in chicken muscle.
AB - p70 S6 kinase (p70S6K) is a key enzyme involved in the control of protein
synthesis. We have previously shown that this kinase is insulin sensitive in
chicken muscle despite a relative insulin resistance in the early steps of
insulin receptor signaling in this tissue, particularly with no change in
tyrosine phosphorylation of the insulin receptor substrate 1 (IRS1). The aim of
the present study is to further study the p70S6K pathway in chicken muscle. By
analyzing in silico several kinases involved in the protein kinase B (PKB also
called AKT)/target of rapamycin (TOR)/p70S6K pathway in the chicken, we showed
that the amino acid sequence of the proteins exhibited a very high identity with
their homologs in mammalian species and Drosophila. We investigated the
regulation of these kinases in vivo or in vitro. Refeeding and insulin treatment
significantly (P<0.05) increased the phosphorylation and/or activity of kinases
upstream of p70S6K such as AKT and TOR. Similarly, refeeding and insulin
increased the phosphorylation of p70S6K on key residues (i.e. T389, T229 and
T421/S424) and the phosphorylation of a p70S6K downstream target, the ribosomal
protein S6 (by 3-10-fold, P<0.05). Interestingly, we also showed an increase in
the phosphorylation level of IRS1 on S632/S635, sites involved in insulin
resistance. In conclusion, the AKT/TOR/p70S6K pathway is activated by refeeding
and insulin injection, which might negatively regulate IRS1 tyrosine
phosphorylation. These results indicate some particularities of the insulin
signaling in chicken muscle and suggest the involvement of p70S6K in these
features.
PMID- 17029675
TI - Modeling growth factor activity during proinflammatory stress: methodological
considerations in assessing cytokine modulation of IGF binding proteins released
by cultured bovine kidney epithelial cells.
AB - The present research was conducted to model potential mechanisms through which
IGFBPs might be affected by a key proinflammatory response initiating cytokine
tumor necrosis factor (TNF-)-alpha. Madin-Darby bovine kidney epithelial (MDBK)
cells, known to release IGFBPs in response to several stimuli, were grown under
several conditions and challenged with forskolin (F) or recombinant TNF-alpha for
24h. Forskolin increased IGFBP-3 gene expression and media content of BP-3
protein. TNF-alpha increased basal and augmented F-mediated IGFBP-3 gene
expression. However, TNF-alpha effects on the measurable media content of IGFBPs
were influenced by culture conditions; in the absence of added protease
inhibitors (PIs) or sufficient media albumin concentration (high BSA, 1mg/ml),
the effect of TNF-alpha was to decrease (P<0.02) measurable IGFBPs. In the
presence of PI and high BSA, media IGFBP-3 levels were shown to be increased by
TNF-alpha consistent with the gene expression data. Changes in media IGFBP-3
protease activity were examined further to explain the observed effects of TNF
alpha on production and destruction of IGFBPs in media. When recombinant human
IGFBP-3 (500 ng/ml) was added to PI-free, low BSA 100 microg/ml) media from TNF
treated MDBK cells, less than 10% of the BP-3 was recognizable by Western blot in
30 min; conversely, inclusion of High BSA and PI in media resulted in attenuation
of the protease effect on the IGFBPs. The data suggest that the MDBK model of
cellular response to proinflammatory stimulus is affected by culture conditions
and that TNF-alpha affects media content of IGFBPs through effects on IGFBP gene
expression coupled with degradation of IGFBPs via enhanced proteolytic enzyme
release.
PMID- 17029676
TI - Decreased ACTH secretion during prolonged transportation stress is associated
with reduced pituitary responsiveness to tropic hormone stimulation in cattle.
AB - The present study examined the effect of transportation stress on hypothalamic
pituitary-adrenal axis responsiveness to tropic hormone stimulation and on
abundance of corticotropin releasing factor (CRF) receptor R1 (CRFR1) and
arginine vasopressin (AVP) receptor V3 (V3) mRNAs in the anterior pituitary (AP)
of cattle. Holstein steers were transported for 10 h or used as non-transported
controls (NTC). Blood samples were collected at start of transportation and every
1-2h thereafter. To test AP responsiveness to tropic hormones, animals were
challenged (i.v.) with CRF (0.5 microg/kg), AVP (1 microg/kg) or CRF plus AVP
immediately after end of transportation and blood samples collected every 30 min
for 3h. The AP of animals transported for 0, 4 or 10 h were harvested for mRNA
analyses. Plasma ACTH in transported animals increased within 1h and remained
elevated for 6 and 8h versus NTC and 0 h values, respectively. Plasma
concentrations of cortisol increased in response to transportation and remained
elevated throughout the transport period. Injection of CRF or AVP to NTC animals
increased plasma ACTH, but ACTH secretion in response to CRF or AVP was
dramatically reduced in transported animals. ACTH secretion following co
injection of CRF and AVP tended to be less in transported animals, but was almost
100% greater than when secretagogues were administered separately. Despite
decreased AP responsiveness to CRF and AVP, AP CRFR1 and V3 mRNAs were increased
after 10 h transportation. Results indicate decreased AP responsiveness to CRF
and AVP may regulate duration of ACTH secretion in response to transportation
stress in cattle.
PMID- 17029677
TI - Effect of improved nutrition during calfhood on serum metabolic hormones,
gonadotropins, and testosterone concentrations, and on testicular development in
bulls.
AB - The objective of the present study was to evaluate the effects of improved
nutrition during calfhood on serum metabolic hormones, gonadotropins and
testosterone concentrations, and on sexual development in bulls. Bulls received
high (n=17) or control nutrition (n=16) diets from 10 to 30 week of age and the
same control nutrition diet from 31 to 74 week of age. Improved nutrition during
calfhood resulted in a more sustained period of elevated LH secretion (pulse
frequency and total secretion in 10h) during the early gonadotropin rise. GnRH
stimulated LH secretion was not affected by diet, indicating that pituitary
responsiveness was not altered; therefore, improved nutrition had direct effects
on GnRH secretion by the hypothalamus. Insulin and insulin-like growth factor-I
(IGF-I) concentrations were greater during calfhood in bulls receiving high
nutrition, indicating that these metabolic hormones might be involved in
regulating GnRH and LH secretion. Improved nutrition also resulted in increased
testosterone secretion that was associated with greater circulating IGF-I
concentrations, suggesting a role for this metabolic hormone in regulating Leydig
cell number and function. Furthermore, improved nutrition during calfhood
resulted in greater testicular weight and sperm production in mature bulls,
indicating that increased LH secretion during calfhood, and increased IGF-I and
testosterone concentrations during calfhood and peripubertal period were
associated with greater testicular cell proliferation and enhanced function.
PMID- 17029678
TI - [Practice of the thromboembolic disease prophylaxis: a survey among surgeons and
anaesthetists in Togo].
AB - OBJECTIVE: The aim of this study was to analyse the current practice of
postoperative venous thromboembolism (VTE) prophylaxis among anaesthetists, nurse
anaesthetist and general surgeons in Togo. METHOD: A total of 160 questionnaires
were distributed to anaesthetists and surgeons with varying subspeciality
interests. RESULTS: One hundred and three (64%) (3 anaesthetists, 51 nurse
anaesthetists and 49 surgeons) returned the questionnaire. Of these, 16% thought
that VTE was as common in Togo as in the western countries. Selective VTE
prophylaxis was used by 78% of the prescriptors. In order of frequency,
indications for selective VTE prophylaxis were obesity, increased risk of VTE
related to surgery and past medical history of VTE. Orthopaedic surgery,
caesarean section and vascular surgery were most frequently considered as high
risk surgery for VTE event. When prophylaxis was indicated, low molecular weight
heparin was prescribed by 87% of prescriptors. In most cases, VTE prophylaxis
duration was less than a week. In 92% of institutions, there was no written
protocol for VTE prophylaxis. VTE-related morbidity was reported by 34% of the
prescriptors over the past year, and 30% of these cases were fatal; 60% of the
prescriptors observed these complications one week after the surgery. CONCLUSION:
The practice of VTE prophylaxis in Togo is not sufficient. It is necessary to
promote the training of practitioners, particularly of physicians.
PMID- 17029679
TI - [ICU performance: results of a French study involving 80,000 ICU stays].
AB - OBJECTIVE: The Standard Mortality Ratio (SMR), comparing the observed in-hospital
mortality to the predicted, may measure the intensive care units (ICU)
performance. STUDY DESIGN: Multicentric retrospective national study. METHODS: A
probability model using a severity score such SAPS II calculated the predicted
mortality rate. A national French study has been undertaken to compare the SMR of
ICUs and looked for explanation. RESULTS: One hundred six units, 34 were medical
(32%), 18 surgical (17%) and 57 medical/surgical (51%) participated to the study.
Forty-six ICUs (43%) were located in teaching hospitals. The SMR of the 87,099
stays was 0.84 (0.82-0.85). The SMR of ICUs varied from 0.41 to 1.55. Ten units
had a SMR>0.85, which suggested a low performance. They had more stays for
cardiovascular failures, as compared with others. The best units (SMR<0.82) had
more stays for drug overdose. The SMR increased with the number of organ
failures, from 0.47 with zero failure to 1.11 with 4 or more organ failures. The
stays with cardiovascular failure, either unique or associated, had a higher SMR.
The 7935 stays with a drug overdose had a SMR of 0.12 (0.10-0.14), which
suggested a bad calibration of the model in theses cases. CONCLUSION: The case
mix must be taken in account when comparing the ICUs performance by the mean of
SMR, particularly when the units admitted a lot of drug overdoses.
PMID- 17029680
TI - Accumulation patterns of organochlorines in juveniles of Arctocephalus australis
found stranded along the coast of Southern Brazil.
AB - The present study was conducted to elucidate the specific distributions of
organochlorine (OC) compounds in various tissues and organs of juveniles of the
South American fur seal (Arctocephalus australis) found stranded on beaches in
southern Brazil. The OC residue concentrations occurred in the following order:
PCBs>DDTs>CHLs>HCHs>HCB. OC concentrations in blubber were higher than other
tissues (e.g. PCBs, 2480 ng g(-1) wet weight; DDTs, 660 ng g(-1) wet weight)
indicating a positive association with lipid content (except for HCB). However,
the poor nutritional status of these animals, possibly following a starvation
period, is likely to have allowed the remobilization of organochlorines stored in
lipids to other tissues throughout the body, increasing their vulnerability to
toxic effects and possibly affecting their survival capability.
PMID- 17029681
TI - Characterization of TSP-bound n-alkanes and polycyclic aromatic hydrocarbons at
rural and urban sites of Tianjin, China.
AB - Total suspended particle (TSP) was collected and analyzed at rural and urban
sites in Tianjin, China during the domestic heating season (from 15 November to
15 March) of 2003/4 for n-alkanes and 16 polycyclic aromatic hydrocarbons (PAHs).
The normalized distribution of n-alkanes with the peak at C22, C23, C24 or C25
suggested that fossil fuel utilization was the major source of particulate n
alkanes at both sites. PAHs normalized distribution for each sample was similar
and the higher molecular weight PAH dominated the profile (around 90%) indicating
a stronger combustion source at both sites. Precipitation and wind were the most
important meteorological factors influencing TSP and PAHs atmospheric
concentrations. In the urban area the emission height had significant influence
on PAHs levels at different heights under the relative stable atmospheric
conditions. Coal combustion was the major source for TSP-bound PAHs at both sites
based on some diagnostic ratios.
PMID- 17029682
TI - Uptake of oxytetracycline and its phytotoxicity to alfalfa (Medicago sativa L.).
AB - A series of experiments were conducted in a hydroponic system to investigate the
uptake of oxytetracycline (OTC) and its toxicity to alfalfa (Medicago sativa L.).
OTC inhibited alfalfa shoot and root growth by up to 61% and 85%, respectively.
The kinetics of OTC uptake could be well described by Michaelis-Menten equation
with Vmax of 2.25 micromol g-1 fresh weight h-1, and Km of 0.036 mM. The uptake
of OTC by alfalfa was strongly inhibited by the metabolic inhibitor, 2,4-DNP (2,4
dinitrophenol), at pH 3.5 and 6.0, but not by the aquaporin competitors, glycerol
and Ag+. OTC uptake, however, was significantly inhibited by Hg2+, suggesting
that the inhibition of influx was due to general cellular stress rather than the
specific action of Hg2+ on aquaporins. Results from the present study suggested
that OTC uptake into alfalfa is an energy-dependent process.
PMID- 17029683
TI - In situ studies on the distribution patterns and dynamics of microcystins in a
biomanipulation fish--bighead carp (Aristichthys nobilis).
AB - The distribution and dynamics of microcystins in various organs of the
phytoplanktivorous bighead carp were studied monthly in Lake Taihu, which is
dominated by toxic cyanobacteria. There was a good agreement between LC-MS and
HPLC-UV determinations. Average recoveries of spiked fish samples were 63% for MC
RR and 71% for MC-LR. The highest MC contents in intestine, liver, kidney and
spleen were 85.67, 2.83, 1.70 and 1.57 microg g-1 DW, respectively. MCs were much
higher in mid-gut walls (1.22 microg g-1 DW) than in hind- and fore-gut walls
(0.31 and 0.18 microg g-1 DW, respectively), suggesting the importance of mid-gut
wall as major site for MC absorption. A cysteine conjugate of MC-LR was detected
frequently in kidney. Among the muscle samples analyzed, 25% were above the
provisional tolerable daily intake level by WHO. Bighead is strongly resistant to
microcystins and can be used as biomanipulation fish to counteract cyanotoxin
contamination in eutrophic waters.
PMID- 17029684
TI - Nutrient losses from manure and fertilizer applications as impacted by time to
first runoff event.
AB - Nutrient losses to surface waters following fertilization contribute to
eutrophication. This study was conducted to compare the impacts of fertilization
with inorganic fertilizer, swine (Sus scrofa domesticus) manure or poultry
(Gallus domesticus) litter on runoff water quality, and how the duration between
application and the first runoff event affects resulting water quality.
Fertilizers were applied at 35 kg P ha-1, and the duration between application
and the first runoff event varied between 1 and 29 days. Swine manure was the
greatest risk to water quality 1 day after fertilization due to elevated
phosphorus (8.4 mg P L-1) and ammonium (10.3 mg NH4-N L-1) concentrations;
however, this risk decreased rapidly. Phosphorus concentrations were 2.6 mg L-1
29 days after fertilization with inorganic fertilizer. This research demonstrates
that manures might be more environmentally sustainable than inorganic
fertilizers, provided runoff events do not occur soon after application.
PMID- 17029685
TI - Simulation of stomatal conductance for Aleppo pine to estimate its ozone uptake.
AB - The data from a previous experiment carried out in open-top chambers to assess
the effects of ozone (O3) exposure on growth and physiology of Aleppo pine (Pinus
halepensis Mill.) were re-assessed to test the performance of the EMEP O3
stomatal conductance model used to estimate tree O3 uptake at a European scale.
Aleppo pine seedlings were exposed during three consecutive years to three
different O3 treatments: charcoal filtered air, non-filtered air and non-filtered
air supplemented with 40 nl l(-1). The results of the model using the default
parameterisation already published for Mediterranean conifers showed a poor
performance when compared to measured data. Therefore, modifications of g(max),
f(min), and new f(VPD), f(temp) and f(phen) functions were developed according to
the observed data. This re-parameterisation resulted in a significant improvement
of the performance of the model when compared to its original version.
PMID- 17029686
TI - Showing similarity of results given by two methods: a commentary.
AB - There is a frequent need in the environmental sciences to show the similarity of
the results given by two analytical methods. This cannot, however, be done within
the conventional 'there is a difference' statistical hypothesis setting of, among
others, Student's t-test. We demonstrate here a more appropriate approach that
originates from drug testing and that can be applied with standard statistical
software. It is a challenging approach, as it requires quantification of the
similarity limit. If no pre-determined value is given for similarity, a potential
data-supported similarity limit can be explored from the data. The approach has
numerous other potential application areas, e.g. parallelism of regression
slopes, homogeneity of variances and lack of interaction.
PMID- 17029687
TI - The ATP-binding cassette transporter ABCA2 as a mediator of intracellular
trafficking.
AB - ATP-binding cassette (ABC) transporters are a family of proteins that translocate
molecules across cellular membranes. Substrates can include lipids, cholesterol
and drugs. Mutations in ABC transporter genes can cause human pathologies and
drug resistance phenotypes in cancer cells. ABCA2, the second member the A sub
family to be identified, was found at high levels in ovarian carcinoma cells
resistant to the anti-cancer agent, estramustine (EM). In vitro models with
elevated levels of ABCA2 are resistant to a variety of compounds, including
estradiol, mitoxantrone and a free radical initiator, 2,2'-azobis-(2
amidinopropane) (AAPH). ABCA2 is most abundant in the central nervous system
(CNS), ovary and macrophages. Enhanced expression of ABCA2 and related proteins,
including ABCA1, ABCA4 and ABCA7, is found in human macrophages upon bolus
cholesterol treatment. ABCA2 also plays a role in the trafficking of low-density
lipoprotein (LDL)-derived free cholesterol and is coordinately expressed with
genes involved in cholesterol homeostasis. Additionally, ABCA2 expression has
been linked with gene cluster patterns consistent with pathologies including
Alzheimer's disease (AD). A single-nucleotide polymorphism (SNP) in exon 14 of
the ABCA2 gene was shown to be linked to early onset AD in humans, supporting the
observation that ABCA2 expression influences levels of beta-amyloid peptide
(Abeta), the primary component of senile plaques. ABCA2 may play a role in
cholesterol transport and affect a cellular phenotype conducive to the
pathogenesis of a variety of human diseases including AD, atherosclerosis and
cancer.
PMID- 17029688
TI - The modified Location Learning Test: norms for the assessment of spatial memory
function in neuropsychological patients.
AB - This study examines the applicability of the modified Location Learning Test
(mLLT) as a test of spatial memory in neuropsychological patients. Three groups
of participants were examined: stroke patients, patients with diabetes mellitus
and healthy participants (N=411). Three error measures were computed, the Total
Score (index of overall performance), the Learning Index (the learning curve over
subsequent trials) and the Delayed Recall Score, measuring decay over time. The
Learning Index was the most sensitive measure, showing differences between the
three groups as well as lateralization effects within the stroke group. Also, the
mLLT correlated significantly with the Rey Auditory Verbal Learning Test, as well
as with age and education level. Regression-based normative data were computed
based on the healthy participants. In all, the mLLT appears to be a sensitive and
valid test for the detection of object-location memory impairments in clinical
groups.
PMID- 17029689
TI - Violent, caring, unpredictable: public views on survivors of brain injury.
AB - The purpose of the present work was to investigate how members of the public
perceived survivors of brain injury. A 20-item list of attributes that could be
used to describe characteristics of survivors of brain injury were given to 323
participants. One hundred and sixty-nine psychology students and 154 members of
the public agreed to take part in the study. The effects of group (student and
public), gender and socioeconomic status (low, moderate and high) on the
attributes were assessed. Multivariate analysis of variance showed a
statistically significant difference between the two groups with students holding
more positive perceptions on 15 out of the 20 attributes. No effects of gender or
socioeconomic status were found. The research suggests that members of the public
hold less positive views on survivors of brain injury in respect to intellectual
competency, ability to care and trustworthiness when compared to students.
PMID- 17029690
TI - Genome multiplication as adaptation to tissue survival: evidence from gene
expression in mammalian heart and liver.
AB - To elucidate the functional significance of genome multiplication in somatic
tissues, we performed a large-scale analysis of ploidy-associated changes in
expression of non-tissue-specific (i.e., broadly expressed) genes in the heart
and liver of human and mouse (6585 homologous genes were analyzed). These species
have inverse patterns of polyploidization in cardiomyocytes and hepatocytes. The
between-species comparison of two pairs of homologous tissues with crisscross
contrast in ploidy levels allows the removal of the effects of species and tissue
specificity on the profile of gene activity. The different tests performed from
the standpoint of modular biology revealed a consistent picture of ploidy
associated alteration in a wide range of functional gene groups. The major
effects consisted of hypoxia-inducible factor-triggered changes in main cellular
processes and signaling pathways, activation of defense against DNA lesions,
acceleration of protein turnover and transcription, and the impairment of
apoptosis, the immune response, and cytoskeleton maintenance. We also found a
severe decline in aerobic respiration and stimulation of sugar and fatty acid
metabolism. These metabolic rearrangements create a special type of metabolism
that can be considered intermediate between aerobic and anaerobic. The metabolic
and physiological changes revealed (reflected in the alteration of gene
expression) help explain the unique ability of polyploid tissues to combine
proliferation and differentiation, which are separated in diploid tissues. We
argue that genome multiplication promotes cell survival and tissue regeneration
under stressful conditions.
PMID- 17029691
TI - Comparability work and the management of difference in research synthesis
studies.
AB - The new imperative to be more methodologically inclusive has generated a
burgeoning interest in synthesizing the findings of qualitative and quantitative
studies, or mixed research synthesis. Yet, the very diversity seen to define the
mixed research synthesis enterprise is also considered to defy it as it
intensifies the problem of comparing the seemingly incomparable to enable the
combination of the seemingly uncombinable. We propose here that the research
synthesis enterprise, in general, and the mixed research synthesis enterprise, in
particular, entail comparability work whereby reviewers impose similarity and
difference on the studies to be reviewed. The very study diversity requiring
management does not exist a priori but rather is itself an outcome of
comparability work already done whereby judgments have been made about what
constitutes methodological and topical diversity and uniformity. Conceiving the
research synthesis process as defined by comparability work moves the backstage
interpretive work of systematic review to center stage and, thereby, sets a new
stage for addressing the methodological issues involved. These issues are
explored by reference to the synthesis of empirical studies of antiretroviral
adherence in HIV-positive women in the US.
PMID- 17029693
TI - Intellectual property organizations and pharmaceutical patents in Africa.
AB - This article builds on a previous study which found low numbers of patent
applications for HIV antiretroviral drugs in African countries. A high level of
variation was noted across individual countries, and consequently, the present
study has sought to account for sources of the variation through statistical
analyses. First, a correlation between the number of patents and HIV infection
rate was observed (r=0.448, p<0.001). T-tests identified significantly higher
numbers of patents in national members of two intellectual property organizations
(IPOs)-African Regional Intellectual Property Orginisation (ARIPO) and the
Organisation Africaine de la Propriete Intellectualle (OAPI)-than in countries
who did not belong to an intellectual property organization. The relationship
between IPO membership and number of patents was also statistically significant
in a multivariate Poisson regression. These findings demonstrate that higher
numbers of patents are found in countries where they are more easily filed. This
has important policy implications given the worldwide trend toward increased
recognition of pharmaceutical patents.
PMID- 17029692
TI - Does social capital enhance health and well-being? Evidence from rural China.
AB - Despite increasing acknowledgement that social capital is an important
determinant of health and overall well-being, empirical evidence regarding the
direction and strength of these linkages in the developing world is limited and
inconclusive. This paper empirically examines relationships between social
capital and health and well-being-as well as the suitability of commonly used
social capital measures-in rural China, where rapid economic growth coexists with
gradual and fundamental social changes. To measure social capital, we adopt a
structural/cognitive distinction, whereby structural social capital is measured
by organizational membership and cognitive social capital is measured by a
composite index of trust, reciprocity, and mutual help. Our outcome measures
included self-reported general health, psychological health, and subjective well
being. We adopt multi-level estimation methods to account for our
conceptualization of social capital as both an individual- and contextual-level
resource. Results indicate that cognitive social capital (i.e., trust) is
positively associated with all three outcome measures at the individual level and
psychological health/subjective well-being at the village level as well. We
further find that trust affects health and well-being through pathways of social
network and support. In contrast, there is little statistical association or
consistent pattern between structural social capital (organizational membership)
and the outcome variables. Furthermore, although organizational membership is
highly correlated with collective action, neither is associated with health or
well-being. Our results suggest that policies aimed at producing an environment
that enhances social networks and facilitates the exchange of social support hold
promise for improving the health and well-being of the rural Chinese population.
In addition, China may not have fully taken advantage of the potential
contribution of structural social capital in advancing health and well-being. A
redirection of collective action from economic to social activities may be worth
considering.
PMID- 17029694
TI - Tautomerism, acid-base properties and conformation of methylated analogues of the
promutagenic N4-hydroxycytosine.
AB - UV and NMR spectroscopy were employed to study the tautomerism, acid-base
properties and conformation of the exocyclic N(4)-OH group in 1-methyl-N(4)
hydroxycytosine (1-mOH(4)C), and its methyl derivatives, viz. the fixed imino
forms (1,3-m(2)OH(4)C and 1,3,5-m(3)OH(4)C), the fixed amino form (1,N(4)
m(2)OH(4)C), and analogues sterically constrained to the form syn (1,5
m(2)OH(4)C) or anti (1,3-m(2)OH(4)C) with respect to the ring N(3). Relative to
1,N(4)-m(2)OH(4)C, UV spectroscopy showed that the other analogues were
predominantly imino and that all analogues formed a structurally common cation in
acid medium, with results pointing to approximately 90% population of the imino
species for 1-mOH(4)C and 1,5-m(2)OH(4)C, further supported by NMR spectroscopy.
Both exhibited two sequential dissociations in alkaline medium, the first due to
N(4)-OH, followed by the N(3)-H. (1)H and (13)C NMR spectroscopy showed 1-mOH(4)C
in the conformation syn. With 1,3,5-m(3)OH(4)C, an ;overcrowded' planar molecule
with steric constraints to both the syn and anti conformations, a syn-anti
equilibrium is observed, with a preference of approximately 75% for the anti
rotamer, independently of the polarity of the medium. Exchange between the
rotamers is slow on the NMR time-scale, with a minimal barrier to exchange
exceeding 100 kJ/mol. In low-polar media, the analogues associate as dimers via
O(4)-Hcdots, three dots, centeredO(2) or O(4)-Hcdots, three dots, centeredN(4)
hydrogen bonds, with association constants at ambient temperature of 4.6 (1,3
m(2)OH(4)C), 12.8 (anti 1,3,5-m(3)OH(4)C), 36 (1,5-m(2)OH(4)C), 109 (syn 1,3,5
m(3)OH(4)C) M(-1). Implications of the overall findings to the promutagenic
activities of OH(4)C and OMe(4)C are examined.
PMID- 17029695
TI - Electrophoresis of long DNA molecules in linear polyacrylamide solutions.
AB - Electrophoresis of long DNA (T4 DNA; 166 kb, S. pombe chromosomal DNA; 3-6 Mb) in
linear polyacrylamide solutions was investigated by fluorescence microscopy and
capillary electrophoresis. In the past studies on electrophoresis of long DNA in
a polymer solution, it was reported that DNA migrates in 'U-shape conformation'.
We found that at higher polymer concentrations, the shape of the migrating DNA
changes from U shape to linear shape ('I-shape conformation'). In the migration
mode with the I-shape conformation, the DNA moves with almost constant velocity
and constant shape. However, the migration velocity does depend on the DNA size,
and it is possible to separate DNAs under this I-shape motion. Actually, Mb-sized
DNAs are well separated within 5 min in the region for the I-shape motion by
means of capillary electrophoresis with a DC field. Considering that it takes 20
h to separate Mb-sized DNAs by standard pulsed-field gel electrophoresis (PFGE),
this results will be useful for the separation of giant DNAs.
PMID- 17029696
TI - Mitochondria as an important factor in the maintenance of constant amplitudes of
cytosolic calcium oscillations.
AB - Theoretical models of intracellular calcium oscillations have hitherto focused on
the endoplasmic reticulum (ER) as an internal calcium store. These models
reproduced the large variability in oscillation frequency observed
experimentally. In the present contribution, we extend our earlier model [Marhl
et al., Biophys. Chem., 63 (1997) 221] by including, in addition to the ER,
mitochondria as calcium stores. Simple plausible rate laws are used for the
calcium uptake into, and release from, the mitochondria. It is demonstrated with
the help of this extended model that mitochondria are likely to act in favour of
frequency encoding by enabling the maintenance of fairly constant amplitudes over
wide ranges of frequency.
PMID- 17029697
TI - Monte Carlo studies on potentiometric titration of poly(glutamic acid).
AB - The potentiometric titration of poly(glutamic acid) with special attention to its
helix-coil transition is investigated in terms of the previously developed Monte
Carlo method. The simulations of the potentiometric titration are carried out for
helical and coiled form of the peptide, separately. A cylindrical rod with
spherical ionizable groups is adopted as each conformational model of
poly(glutamic acid) molecule. A spherical charge with a hard core potential is
assumed as a mobile hydrated ion. The helix-coil transition curves are analyzed
by the Zimm-Bragg theory. A satisfactory agreement is achieved for the titration
curves with the experimental data in most cases. The significance and the
limitations of the simulation method are discussed.
PMID- 17029698
TI - On the need to consider kinetic as well as thermodynamic consequences of the
parking problem in quantitative studies of nonspecific binding between proteins
and linear polymer chains.
AB - Attention is drawn to a need for caution in the thermodynamic characterization of
nonspecific binding of a large ligand to a linear acceptor such as a
polynucleotide or a polysaccharide-because of the potential for misidentification
of a transient (pseudoequilibrium) state as true equilibrium. The time course of
equilibrium attainment during the binding of a large ligand to nonspecific three
residue sequences of a linear acceptor lattice has been simulated, either by
numerical integration of the system of ordinary differential equations or by a
Monte Carlo procedure, to identify the circumstances under which the kinetics of
elimination of suboptimal ligand attachment (called the parking problem) create
such difficulties. These simulations have demonstrated that the potential for the
existence of a transient plateau in the time course of equilibrium attainment
increases greatly (i) with increasing extent of acceptor saturation (i.e., with
increasing ligand concentration), (ii) with increasing magnitude of the binding
constant, and (iii) with increasing length of the acceptor lattice. Because the
capacity of the polymer lattice for ligand is most readily determined under
conditions conducive to essentially stoichiometric interaction, the parameter so
obtained is thus likely to reflect the transient (irreversible) rather than
equilibrium binding capacity. A procedure is described for evaluating the
equilibrium capacity from that irreversible parameter; and illustrated by
application to published results [M. Nesheim, M.N. Blackburn, C.M. Lawler, K.G.
Mann, J. Biol. Chem. 261 (1986) 3214-3221] for the stoichiometric titration of
heparin with thrombin.
PMID- 17029699
TI - Actinic light and pH effect on the proton pumping of bacteriorhodopsin.
AB - The actinic light effect on the bacteriorhodopsin (BR) photocycle kinetics led to
the assumption of a cooperative interaction between the photocycling BR
molecules. In this paper we report the results of the actinic light effect and pH
on the proton release and uptake kinetics. An electrical method is applied to
detect proton release and uptake during the photocycle [E. Papp, G. Fricsovszky,
J. Photochem. Photobiol. B: Biol. 5 (1990) 321]. The BR photocycle kinetics was
also studied by absorption kinetics measurements at 410 nm and the data were
analyzed by the local analysis of the M state kinetics [E. Papp, V.H. Ha,
Biophys. Chem. 57 (1996) 155]. While at high pH and ionic strength, we found a
similar behavior as reported earlier, at low ionic strength the light effect
proved to be more complex. The main conclusions are the following: Though the
number of BR excited to the photocycle (fraction cycling, fc) goes to saturation
with increasing laser pulse energy, the absorbed energy by BR increases linearly
with pulse energy. From the local analysis we conclude that the light effect
changes the kinetics much earlier, already at the L intermediate state decay. The
transient electric signal, caused by proton release and uptake, can be decomposed
into two components similarly to the absorption kinetic data of the M
intermediate state. The actinic light energy affects mainly the ratio of the two
components and the proton movements inside BR while pH has an effect on the
kinetics of the proton release and uptake groups at the membrane surface.
PMID- 17029700
TI - Receptor regulation in neuroendocrine-immune communication: current knowledge and
future perspectives.
AB - Immune cells express receptors for every hormone or neurotransmitter we know so
far. The neuroendocrine system signals to the immune system via the release of
hormones and neurotransmitters that regulate cellular activity via these
receptors. Much attention has been focused on the effect of glucocorticoids and
catecholamines on the immune system. Glucocorticoids communicate with immune
cells via glucocorticoid receptors of which the activity itself changes during
immune activation. Many neuroendocrine mediators are ligands for G-protein
coupled receptors on immune cells. Cytokines, oxygen-radicals, and catecholamines
can influence the responsiveness of G-protein coupled receptors via decreasing
the intracellular level of so-called G-protein coupled receptor kinases, of which
the subtype GRK2 is highly expressed in immune cells. Therefore, changes in only
one kinase can modulate the sensitivity of many receptors. We describe here that
sensitivity of neuroendocrine receptors on immune cells is constantly regulated
by inflammatory processes or chronic stress, which implies that not only the
activity of the neuroendocrine system determines communication but that the
sensitivity of receptors is a major factor in determining the final immune
response. Finally, consequences of alterations in GRK2 during (neuro)
inflammatory diseases are discussed.
PMID- 17029701
TI - Maternal antibrain antibodies in autism.
AB - Autism is a neurodevelopmental disorder of prenatal onset that is behaviorally
defined. There is increasing evidence for systemic and neuroimmune mechanisms in
children with autism. Although genetic factors are important, atypical prenatal
maternal immune responses may also be linked to the pathogenesis of autism. We
tested serum reactivity in 11 mothers and their autistic children, maternal
controls, and several groups of control children, to prenatal, postnatal, and
adult rat brain proteins, by immunoblotting. Similar patterns of reactivity to
prenatal (gestational day 18), but not postnatal (day 8) or adult rat brain
proteins were identified in autistic children, their mothers, and children with
other neurodevelopmental disorders, and differed from mothers of normal children,
normal siblings of children with autism and normal child controls. Specific
patterns of antibody reactivity were present in sera from the autism mothers,
from 2 to 18 years after the birth of their affected children and were unrelated
to birth order. Immunoblotting using specific antigens for myelin basic protein
(MBP) and glial acidic fibrillary protein (GFAP) suggests that these proteins
were not targets of the maternal antibodies. The identification of specific serum
antibodies in mothers of children with autism that recognize prenatally expressed
brain antigens suggests that these autoantibodies could cross the placenta and
alter fetal brain development.
PMID- 17029702
TI - Poor sleep the night before an experimental stressor predicts reduced NK cell
mobilization and slowed recovery in healthy women.
AB - Sleep is important for health; however, poor sleep is a growing problem in many
Western societies, particularly among women. Alterations in immune function
following poor sleep (defined by duration and disruption) may be linked to ill
health. Not yet investigated are the possible effects on stress-induced
mobilization of lymphocytes. As natural killer (NK) cells are particularly
responsive to acute stress, the present study examined whether sleep period
duration and percentage of time awake after sleep onset (WASO) the night before a
laboratory stressor would predict reduced NK cell mobilization. Sleep was
monitored by actigraphy in 39 healthy women. NK cell peripheral blood numbers
were determined at baseline (post-20 min rest), 4 min into a Stroop task,
immediately post-task and 30 min after task completion. Participants with high
WASO had significantly less NK cell mobilization to the stressor and failed to
return to baseline levels after 30 min compared to women with low WASO. No
effects were found for sleep period duration. Findings raise the possibility that
inadequate NK cell mobilization to, and poor recovery from acute stress may be
one pathway by which sleep could impact health.
PMID- 17029703
TI - Psychosocial stress increases inflammatory markers and alters cytokine production
across pregnancy.
AB - Previous work has shown that psychosocial stress is related to increases in serum
levels of pro-inflammatory cytokines late in pregnancy, and a growing body of
research suggests that increased inflammatory activity during pregnancy,
generally, may have a negative impact on outcome. The present study further
addressed these issues by assessing relationships between psychosocial stress,
social support and serum cytokines in early, mid, and late pregnancy, and the
effects of stress and social support on the production of cytokines by stimulated
lymphocytes in late pregnancy. In addition, we examined relationships between
stress, support, and serum C-reactive protein (CRP) during pregnancy. Elevated
stress was not only related to higher serum IL-6 late in pregnancy as in our
prior work, but this relationship was also evident during early pregnancy and
elevated stress was also associated with lower IL-10 in early pregnancy. No
relationships between stress and cytokines were apparent during the 2nd trimester
of pregnancy. Elevated stress during the 2nd trimesters and low social support
during the 3rd trimester were related to increased serum levels of CRP, further
suggesting that psychosocial factors can contribute increased inflammation during
pregnancy. Importantly, elevated stress levels across pregnancy were predictive
of elevated production of the pro-inflammatory cytokines IL-1B and IL-6 by
stimulated lymphocytes in the 3rd trimester, suggesting that stress during
pregnancy affects the function of immune system cells. These findings further
support the notion that prenatal stress alters maternal physiology and immune
function in a manner consistent with increased risk of pregnancy complications
such as preeclampsia and premature labor.
PMID- 17029704
TI - Sustained oscillations in glycolysis: an experimental and theoretical study of
chaotic and complex periodic behavior and of quenching of simple oscillations.
AB - We report sustained oscillations in glycolysis conducted in an open system (a
continuous-flow, stirred tank reactor; CSTR) with inflow of yeast extract as well
as glucose. Depending on the operating conditions, we observe simple or complex
periodic oscillations or chaos. We report the response of the system to
instantaneous additions of small amounts of several substrates as functions of
the amount added and the phase of the addition. We simulate oscillations and
perturbations by a kinetic model based on the mechanism of glycolysis in a CSTR.
We find that the response to particular perturbations forms an efficient tool for
elucidating the mechanism of biochemical oscillations.
PMID- 17029705
TI - Oscillations in peroxidase-catalyzed reactions and their potential function in
vivo.
AB - The peroxidase-oxidase reaction has become a model system for the study of
oscillations and complex dynamics in biochemical systems. In the present paper we
give an overview of previous experimental and theoretical studies of the
peroxidase-oxidase reaction. Recent in vitro experiments have raised the question
whether the reaction also exhibits oscillations and complex dynamics in vivo. To
investigate this possibility further we have undertaken new experimental studies
of the reaction, using horseradish extracts and phenols which are widely
distributed in plants. The results are discussed in light of the occurrence and a
possible functional role of oscillations and complex dynamics of the peroxidase
oxidase reaction in vivo.
PMID- 17029706
TI - Calcium waves and oscillations in eggs.
AB - Eggs from several protostomes (molluscs, annelids, nemerteans, etc.) and two
deuterostomes (mammals and ascidians) display repetitive calcium signals.
Oscillations in the level of intracellular calcium concentration are occasionally
triggered by maturing hormones (as in some molluscs) and mostly observed after
fertilization which occurs at different stages of the meiotic cell cycle (oocytes
are arrested in prophase, metaphase I or metaphase II). In most eggs examined so
far, calcium oscillations last until the end of meiosis just before male and
female pronuclei form. This ability depends on the sensitivity of InsP3 channels
and on the permeability of the plasma membrane to extracellular calcium. In eggs
that undergo cytoplasmic reorganization at fertilization (annelids, nemerteans,
ascidians, etc.) the repetitive calcium signals are waves that originate from
localized cortical sites that become calcium waves pacemakers. In ascidians we
have identified the site of initiation of repetitive calcium waves as an
accumulation of endoplasmic reticulum sandwiched between the plasma membrane and
an accumulation of mitochondria. We compare and discuss the generation of calcium
signals in the different eggs, their relationship with the cell cycle and the
possible roles they play during development.
PMID- 17029707
TI - From bistability to oscillations in a model for the isocitrate dehydrogenase
reaction.
AB - Considered is a bienzymatic system consisting of isocitrate dehydrogenase (IDH,
EC 1.1.1.42), which transforms NADP(+) into NADPH, and of diaphorase (DIA, EC
1.8.1.4), which catalyzes the reverse reaction. Experimental evidence as well as
a theoretical model show the possibility of a coexistence between two stable
steady states in this reaction system. The phenomenon originates from the
regulatory properties of IDH. We extend the analysis of a theoretical model
proposed for the IDH-DIA bienzymatic system and investigate the occurrence of
different modes of bistability, with or without hysteresis, i.e. in the presence
of two or only one limit point bounding the domain of multiple steady states. The
analysis indicates that the two types of bistability may sometimes be observed
sequentially as a given control parameter is progressively increased. We further
obtain conditions in which sustained oscillations develop in the model. These
results establish the isocitrate dehydrogenase reaction coupled to diaphorase as
a suitable candidate for further experimental and theoretical studies of
bistability and oscillations in biochemical systems.
PMID- 17029708
TI - Bistability and the species barrier in prion diseases: stepping across the
threshold or not.
AB - The infectious agent of transmissible spongiform encephalopathies is thought to
be a cellular protein, the prion protein, which undergoes, under some
circumstances, a dramatic conformational change leading to pathogenesis. The
conversion between the normal and pathogenic isoforms corresponds to a
autocatalytic mechanism and the metabolism of the prion protein exhibits switches
between a normal, stable steady state and a pathogenic one. When the disease can
be transmitted between two species, a primary infection from a heterologous donor
has to be followed by two passages in the same host species so that the
incubation period is stabilized. Sometimes, no pathogenic isoform of the prion
protein is detected after the first passage, although corresponding brain
extracts remain infectious. The observation that three and only three passages
are needed in order to stabilize the strain strongly suggests that, during the
course of the primary infection by the heterologous donor, an intermediary
conformational species is formed. Within this assumption, a common mechanism
involving only conformational changes of the prion protein can give a unifying
interpretation of the problem of species barrier, lag characteristics and
apparent lack of detection of the pathogenic isoform after the first passage in
experiments dealing with interspecies transmission of prion diseases.
PMID- 17029709
TI - Molecular characterisation of Salmonella strains by an oligonucleotide multiprobe
microarray.
AB - A DNA microarray has been developed for the simultaneous characterisation and
typing of Salmonella enterica subsp. enterica isolates. One-hundred and nine 35
40 mer oligonucleotides probes detect flagellar and somatic antigen encoding
genes (serogroup or serotype specific), important virulence genes located within
or outside the pathogenicity islands, phage-associated genes and antibiotic
resistance determinants. The probes were printed on glass slides and whole
genomic Cy5-labelled Salmonella DNA was hybridised to the substrate. A set of 19
different Salmonella strains and one Escherichia coli strain has been selected as
positive and negative controls for each probe. The validity of the results is
confirmed by gene-specific PCRs or phenotypic methods (serotyping, MIC
determination for various antimicrobial agents). Of 2071 data points generated,
an agreement of 97.4% has been obtained between microarray and PCR/phenotypic
results. Twenty-six data points (1.3%) were classified as uncertain and,
similarly, 1.3% showed a discordant result. The microarray described here is a
new tool to study the epidemiology of Salmonella strains on the genotypic level
and might become a powerful method in risk assessment studies.
PMID- 17029710
TI - Neuropsychological sequelae from acute poisoning and long-term exposure to
carbamate and organophosphate pesticides.
AB - This research examines the effects of different degrees of pesticide exposure on
neuropsychological performance. Exposures varied from acute poisoning coupled
with chronic exposure to low or high levels of chronic exposure (defined by years
of exposure). A cross-sectional neuropsychological and biochemical study was
conducted in greenhouse farmers from southern Spain: data from 24 acutely
poisoned workers and 40 non-poisoned but chronically (low or high) exposed
sprayers were compared to 26 controls. We examined performance on 21
neuropsychological tests that assessed attention, memory, praxis, gnosis, motor
coordination, naming and reasoning and also examined values of plasmatic
cholinesterase. Results indicated statistically significant neuropsychological
deficits in the acute poisoning and high chronic exposure groups after
controlling for confounds, whereas similar performance was seen in the low
chronic exposed subjects and controls. Subjects who were acutely poisoned
performed worse than the other groups on perceptual, visuomotor, visual memory
and mood state domains. Both the acutely poisoned and the chronically high
exposed subjects obtained significantly lower scores in the perceptual, verbal
memory and visuomotor domains. Levels of butyrylcholinesterase were related to
the seasonal sprayer activity except in the case of acutely poisoned subjects.
CONCLUSIONS: Both acutely poisoned long-term workers and chronically high (>10
years) exposed workers exhibited similar disturbances in perception and visuo
motor processing, in the absence of any related acute effect of
butyrylcholinesterase inhibition. In the case of acutely poisoned subjects,
verbal and perceptive learning and recall and constructive abilities were also
impaired. These results point to the need for follow-up studies to assess the
possible sequelae of chronic and acute exposure to pesticides and their
interactions.
PMID- 17029711
TI - Anaerobic stopped-flow studies of indole-3-acetic acid oxidation by dioxygen
catalysed by horseradish C and anionic tobacco peroxidase at neutral pH: catalase
effect.
AB - The effect of order of reagent mixing in the absence and in the presence of
catalase on the transient kinetics of indole-3-acetic acid (IAA) oxidation by
dioxygen catalysed by horseradish peroxidase C and anionic tobacco peroxidase at
neutral pH has been studied. The data suggest that haem-containing plant
peroxidases are able to catalyse the reaction in the absence of exogenous
hydroperoxide. The initiation proceeds via the formation of the ternary complex
enzyme-->IAA-->oxygen responsible for IAA primary radical generation. The
horseradish peroxidase-catalysed reaction is independent of catalase indicating a
significant contribution of free radical processes into the overall mechanism.
This is in contrast to the tobacco peroxidase-catalysed reaction where the
peroxidase cycle plays an important role. The transient kinetics of IAA oxidation
catalysed by tobacco peroxidase exhibits a biphasic character with the first
phase affected by catalase. The first phase is therefore associated with the
common peroxidase cycle while the second is ascribed to native enzyme interaction
with skatole peroxy radicals yielding directly Compound II.
PMID- 17029712
TI - Computer simulation of damped oscillations during peroxidase-catalyzed oxidation
of indole-3-acetic acid.
AB - Oscillation patterns in horseradish peroxidase (HRP)-catalyzed oxidation of
indole-3-acetic acid (IAA) at neutral pH were studied using computer simulation.
Under certain conditions, such as the presence of a reaction promoter and
continuous intake of oxygen from the gaseous phase, the simulated system exhibits
damped oscillations of the concentrations of oxygen in the aqueous phase,
[O(2)](aq), and of all the reaction intermediates. The critical concentration of
oxygen in aqueous phase, [O(2)](cr)(aq), was used to describe the nature of the
oscillations. The critical concentration is the concentration at which the system
abruptly changes its properties. If [O(2)](aq) is higher than [O(2)](cr)(aq) then
the reaction develops as an avalanche, otherwise, the reaction stops. The nature
of oscillations is accounted for by the interaction of two processes: the
consumption/accumulation of oxygen and the accumulation/consumption of reaction
intermediates. Oscillations are always damped. Neither HRP or umbelliferone (Umb)
deactivation nor IAA consumption can account for the damping. The nature of the
damping is determined by the termination reactions of free radical intermediates
and ROOH. The three major parameters of oscillations: period of oscillations,
initial amplitude of oscillations and the rate of damping were studied as
functions of: (i) oxygen concentration in the gaseous phase, (ii) initial oxygen
concentration in aqueous phase, (iii) the concentration of IAA and (iv) the
initial concentration of HRP.
PMID- 17029713
TI - Neural network explanation using inversion.
AB - An important drawback of many artificial neural networks (ANN) is their lack of
explanation capability [Andrews, R., Diederich, J., & Tickle, A. B. (1996). A
survey and critique of techniques for extracting rules from trained artificial
neural networks. Knowledge-Based Systems, 8, 373-389]. This paper starts with a
survey of algorithms which attempt to explain the ANN output. We then present
HYPINV, a new explanation algorithm which relies on network inversion; i.e.
calculating the ANN input which produces a desired output. HYPINV is a
pedagogical algorithm, that extracts rules, in the form of hyperplanes. It is
able to generate rules with arbitrarily desired fidelity, maintaining a fidelity
complexity tradeoff. To our knowledge, HYPINV is the only pedagogical rule
extraction method, which extracts hyperplane rules from continuous or binary
attribute neural networks. Different network inversion techniques, involving
gradient descent as well as an evolutionary algorithm, are presented. An
information theoretic treatment of rule extraction is presented. HYPINV is
applied to example synthetic problems, to a real aerospace problem, and compared
with similar algorithms using benchmark problems.
PMID- 17029714
TI - Contributions of dipole moments, quadrupole moments, and molecular
polarizabilities to the anesthetic potency of fluorobenzenes.
AB - Previous studies have emphasized the role of molecular polarizability and
electric moments, especially dipole and quadrupole moments, in binding of drugs
to sites of action. A recent publication of ED50s that prevent response to a
noxious stimulus for eight fluorobenzenes has made it possible to compare
anesthetic potency with ab initio Hartree-Fock calculations of molecular
polarizability as well as dipole and quadrupole moments. Fluorobenzenes provide a
stringent test of the role of electric moments in anesthetic potency because
individual dipole moments range from 0 to 2.84 debye (D) while the quadrupole
moment of benzene is large and negative (-30 x 10(-40) C m(2)), that of
hexafluorobenzene is large and positive (30 x 10(-40) C m(2)), and that of 1,3,5
trifluorobenzene is nearly zero. We found that anesthetic potency of
fluorobenzenes was not affected by the presence of either dipole or quadrupole
moments. This result is surprising because fluoroalkanes and fluorocycloalkanes
are most potent when half fluorinated and are usually not anesthetics when
perfluorinated. The results suggest that electrostatic interactions are not
important for binding of fluorobenzenes at sites of anesthetic action and that
these sites are different from those that bind conventional anesthetics.
PMID- 17029715
TI - An experimental methodology for measuring volume changes in proton transfer
reactions in aqueous solutions.
AB - A fast perturbation in proton concentration can be induced in aqueous solution
using a pulsed ultraviolet laser and suitable photolabile compounds which, upon
photoexcitation, irreversibly release protons. The volume change and the rate
constant for the reaction of the photodetached protons with proton-accepting
groups in solution can be monitored using time resolved photoacoustics. A typical
proton concentration jump of 1 microM can be obtained with a 200-microJ laser
pulse at 308 nm. Reaction dynamics from 20 ns to 5 micros can be easily followed.
The methodology we establish represents a direct, time-resolved measurement of
the reaction volume in proton transfer processes and an extension to the
nanosecond-microsecond range of traditional relaxation techniques, such as
stopped-flow. We report example applications to reactions involving simple
molecules and polypeptides.
PMID- 17029716
TI - Effect of the cation and the anion of an electrolyte on the solubility of DL
aminobutyric acid in aqueous solutions: measurement and modelling.
AB - The solubilities at 298.2 K of dl-aminobutyric acid in aqueous solutions of NaCl,
KCl, NaNO(3) and KNO(3) were measured. The solubility of DL-aminobutyric acid was
found to be influenced by the concentration and by the nature of both the cation
and the anion of the electrolyte. Comparison of the results obtained in this
study and those for other amino acids reported in the literature, indicates that
the structure of the hydrocarbon backbone of an amino acid plays an important
role in the interactions of an amino acid with an electrolyte. A thermodynamic
model has been used to correlate the solubilities of DL-aminobutyric acid in
aqueous electrolyte solutions. The activity coefficients of the amino acid in the
electrolyte solutions, were represented by a model proposed by Khoshkbarchi and
Vera [M.K. Khoshkbarchi, J.H. Vera, AIChE J. 42 (1996) 2354; M.K. Khoshkbarchi,
J.H. Vera, Ind. Eng. Chem. Res. 35 (1996) 4755]. This model, which considers a
combination of both long- and short-range interactions, contains only two
adjustable parameters. All other parameters are available in the literature. The
model can accurately correlate the solubility of dl-aminobutyric acid in aqueous
solutions of electrolytes.
PMID- 17029717
TI - Dynamic model of hormonal systems coupled by negative feedback.
AB - Most hormone concentrations in the body are regulated by negative feedback
mechanisms in which the production and release of hormones are regulated
according to the concentration of related species. Also, it has been observed
that several hormones are released in a variety of pulsatile patterns. In most
cases, the mechanism driving these complex patterns is not well understood. Our
model of two cells coupled through negative feedback to their external products
demonstrates periodic, aperiodic and chaotic oscillations. The coupling between
the cells seems to be responsible for these dynamic behaviors. The variety of
dynamic behaviors observed in the model demonstrates that a simple physiological
feedback loop mimicking the coupling between circulatory hormones and production
centers could be the source of complex hormone release patterns observed in vivo.
PMID- 17029718
TI - Rigid-body oscillations of alpha-helices: implications for protein thermal
stability.
AB - A quasi-continuity model protein consisting of two alpha-helices undergoing rigid
body torsional oscillations demonstrates that factors stabilizing the model
protein, such as increased helix rigidity and hydrophobicity, are the same
factors that stabilize thermophilic proteins relative to their mesophilic
analogs. The model predicts oscillatory motions with frequencies in the microwave
(10(10) Hz) range. These oscillations decrease in frequency with increasing helix
rigidity because of compensating increases in the force constant and moment of
inertia, thus explaining the retention of activity in the more rigid thermophilic
enzymes. Implications for protein design, based on the predictions of the model,
are discussed.
PMID- 17029719
TI - (17)O NMR of water in ordered environments.
AB - Two NMR experiments are designed for selective excitation of spin I=5/2 nuclei
that exhibit residual quadrupolar splittings. The I=5/2 Jeener-Broekaert
experiment is preferred to the four-quantum filtration experiment as it is shown
to be a more sensitive technique in experimental practice. Both techniques are
applied to (17)O-enriched water in biological systems. The occurrence of water
which displays a residual (17)O quadrupolar splitting is demonstrated for the
first time in a model biological system and an excised tissue sample. The
resulting (17)O NMR spectra are shown to have the characteristics predicted in
computer-simulated I=5/2 NMR spectra.
PMID- 17029720
TI - Azide accelerates the decay of M-intermediate of pharaonis phoborhodopsin.
AB - Natronobacterium pharaonis has retinal proteins, one of which is pharaonis
phoborhodopsin, abbreviated as ppR (or called pharaonis sensory rhodopsin II, psR
II). This pigment protein functions as a photoreceptor of the negative phototaxis
of this bacterium. On photoexcitation ppR undergoes photocycling; the
photoexcited state relaxes in the dark and returns to the original state via
several intermediates. The photocycle of ppR resembles that of bR except in
wavelengths and rate. The cycle of bR is completed in 10 ms while that of ppR
takes seconds. The Arrhenius analysis of M-intermediate (ppR(M)) decay which is
rate-limiting revealed that the slow decay is due to the large negative
activation entropy of ppR. The addition of azide increases the decay rate 300
fold (at pH 7); Arrhenius analysis revealed decreases in the activation energy
(activation enthalpy) and a further decrease in the activation entropy.
PMID- 17029721
TI - The partial molar heat capacity and volume of the peptide backbone group of
proteins in aqueous solution.
AB - The partial molar heat capacities have been determined for the series of peptides
alanyl(glycyl)(x)glycine, x=1-3, and for the compounds N-acetylglycinamide and N
acetyl glycylglycinamide in aqueous solution over the temperature range 10-100
degrees C using high sensitivity scanning microcalorimetry. The partial molar
volumes for these compounds have also been determined over the temperature range
from 10 to 90 degrees C using a scanning densimetric method. The results were
used to derive the partial molar heat capacities and volumes of the glycyl group
at temperatures in the range 10-100 degrees C. The results obtained are
critically compared with literature results derived using heat capacity and
volume data for some oligoglycines.
PMID- 17029722
TI - The Synthesizing Unit as model for the stoichiometric fusion and branching of
metabolic fluxes.
AB - The Synthesizing Unit (SU) binds given numbers of substrate molecules of several
types of substrate to produce a product molecule or set of product molecules.
Irreversible binding results in relatively simple and explicit expressions for
the rate of product formation. Reversible binding can be implemented with
relative ease in the carrier-SU complex, where the products of a set of carriers
(a special type of SU) serve as substrate for an SU or set of SUs. A simple and
parameter sparse approximation is presented for the production rate of a
generalized compound, i.e. a rich mixture of compounds that does not change in
composition. An analysis of Droop's data on the growth of a haptophyte on
phosphate and vitamin B(12) reserves illustrates the application of SUs.
PMID- 17029723
TI - Orally disintegrating olanzapine for the treatment of a manic patient with
esophageal stricture plus chronic pharyngitis.
AB - An orally disintegrating tablet formulation of olanzapine (ODT olanzapine) is
designed to dissolve rapidly upon contact with saliva. We describe a manic
patient who has an esophageal stricture and chronic pharyngitis, two conditions
that impede the swallowing of medications. She was successfully treated for her
mania with this orally disintegrating formulation. This case report shows that
ODT olanzapine may be useful in the psychiatric management of manic and other
patients for whom olanzapine is appropriate, and who have an underlying medical
condition that impedes swallowing oral medications.
PMID- 17029724
TI - Multistage graph-based segmentation of thoracoscopic images.
AB - This paper presents a graph-based segmentation method using multiple criteria in
successive stages to segment thoracoscopic images acquired during a diskectomy
procedure commonly used for thoracoscopic anterior release and fusion for
scoliosis treatment. Starting with image pre-processing, including Gaussian
smoothing, brightness and contrast enhancement, and histogram thresholding, a
standard graph-based method is applied to produce a coarse segmentation of
thoracoscopic images. Next, regions are further merged in a multistage graph
based process based on features like grey-level similarity, region size and
common edge length. Experimental results show that our approach achieves good
spatial coherence, accurate edge location and appropriate segmentation of the
regions of interest from a sequence of thoracoscopic images.
PMID- 17029725
TI - Placental transfer of polychlorinated dibenzo-p-dioxins, dibenzofurans, and
biphenyls in Taiwanese mothers in relation to menstrual cycle characteristics.
AB - The aim was to determine the body burden of dioxins and polychlorinated biphenyls
(PCBs) and whether they are associated with variables influencing reproduction.
Our subjects were healthy women (mean age of 29 [SD=4.5]) from central Taiwan.
The congeners of dioxins and dioxin-like PCBs in placentas (n=119) were
identified using gas chromatography/high resolution mass spectrometry. The median
levels of polychlorinated dibenzo-p-dioxins/dibenzofurans and PCBs were 10.2
(geometric mean [GM]: 9.8, 95% confidence interval [95% CI]: 8.8-10.9) and 2.7
(GM: 2.7, 95% CI: 2.3-3.1) pg WHO-TEQ/g lipid, respectively. Total TEQ level in
placentas was significantly correlated with mothers' arm circumference (r=0.22,
p=0.043). Increased body fat percentage was associated with higher total TEQ
level in placentas. After adjustment for maternal age, pre-pregnant body mass
index (BMI), and parity, placental dioxin-TEQ level higher in women (age 19
years) with irregular menstrual cycle than in those (age <18 years) with regular
menstrual cycle (p=0.032) and placental PCB-TEQ level was higher in women with
menstrual cycles longer than 33 days versus less than 33 days (p=0.006). Thus,
environmental exposure to dioxins and PCBs may be related to changes in current
menstrual cycle characteristics.
PMID- 17029726
TI - Abrogation of streptococcal pyrogenic exotoxin B-mediated suppression of
phagocytosis in U937 cells by Cordyceps sinensis mycelium via production of
cytokines.
AB - Streptococcal pyrogenic exotoxin B (SPE B) is a virulent factor in group A
streptococcal infection. We previously showed that SPE B reduced phagocytosis in
human monocytic U937 cells. Here we show that the mycelium extract of Cordyceps
sinensis (CS), a Chinese immunomodulatory herbal medicine, increased phagocytosis
in U937 cells. Neither heat nor trypsin pretreatment prevented CS extract from
causing this increase. Further studies indicated that SPE B-mediated suppression
of U937 cell phagocytic activity was abrogated by CS extract. Factors in the
conditioned medium from CS-extract-treated U937 cells were responsible for
blocking the SPE B-mediated suppression of phagocytosis. Heating the conditioned
medium eliminated the increase, which suggested that the U937-cell protein
products augmented phagocytosis. Analyzing cytokine mRNA expression of U937 cells
revealed increases in interferon-gamma (IFN-gamma), interleukin (IL)-12 p35 and
p40, and tumor necrosis factor-alpha (TNF-alpha), but not in IL-1beta, IL-6, or
IL-8. Treating U937 cells with anti-IFN-gamma, IL-12, and TNF-alpha antibodies
also eliminated the conditioned medium-induced increase in phagocytosis. Taken
together, SPE B inhibited phagocytosis, but CS mycelium extract abrogated this
inhibition by causing cytokine production.
PMID- 17029727
TI - Molecular orbital study of porphyrin-substrate interactions in cytochrome P450
catalysed aromatic hydroxylation of substituted anilines.
AB - The reaction mechanism for the primary reaction step of the hydroxylation of 3
fluoro-6-methylaniline, attacked at different positions (oxygen attack across a C
C bond and direct attack at positions para and ortho with respect to the NH(2)
group) catalysed by a high-valent ferryl-oxo porphyrin a(2u)-cation complex with
H(3)CS(-) as an axial ligand, has been investigated on the basis of electronic
structure calculations in local spin-density approximation. Non-repulsive
potential curves are obtained only in cases of direct attack at the para- and
ortho-positions with respect to NH(2), but not for epoxide formation. Comparing
the potential curves for the hydroxylation at the positions para and ortho to the
NH(2)-group, an attack at the para-position is more likely. The relative
orientation of the substrate towards the porphyrin is essentially determined by
the interaction between the substituents of the substrate and the porphyrin.
Consequently, different geometrical orientations of the substrate are obtained
for hydroxylation at the para- and ortho-positions. In both cases of direct
attack the substrate plane is not parallel to the porphyrin plane. The decisive
role of sulphur in the hydroxylation is demonstrated by the participation of the
S(3p)-orbitals in all molecular orbitals involved in the reaction.
PMID- 17029728
TI - Ortho-aminobenzoic acid as a fluorescent probe for the interaction between
peptides and micelles.
AB - Ortho-aminobenzoic acid (o-Abz) has been used as a fluorescent probe in
internally quenched fluorescent peptides for continuous protease assays. We
investigated the fluorescent properties of the probe in order to verify if it can
be used to monitor the interaction of peptides with micelles. Abz-aminoacyl
monomethyl amides (Abz-Xaa-NHCH(3), where Xaa=Arg, Phe, Leu and Glu) were
synthesized. Quantum yield, spectral position, anisotropy and lifetime decay were
analyzed in the presence and absence of sodium dodecyl sulfate (SDS) micelles.
Significant changes in the fluorescence parameters were observed for Abz-Arg
NHCH(3) in comparison to Abz-Glu-NHCH(3), indicating a strong electrostatic
component in the compound's interaction with the negative charged micelles. The
change in fluorescence parameters, observed when the probe is bound to
hydrophobic amino acids Abz-Phe-NHCH(3) and Abz-Leu-NHCH(3), is probably due to
insertion of those compounds into micelles. Abz-NHCH(3) fluorescence is less
affected by the presence of micelles, indicating that the occurrence of
interaction is dependent on the properties of the amino acid to which the
fluorophore is attached. The quenching data with acrylamide confirmed these
results. Titration curves allowed the estimation of association constants between
Abz compounds and SDS, according to a single partition model. Although the
results cannot be strictly applied to the titration with charged compounds, it
was verified that the association constant for the isolated Abz-NHCH(3) is
significantly lower than those for Abz-Phe-NHCH(3) and Abz-Leu-NHCH(3). It is
concluded that the Abz group is a sensitive and convenient fluorescent probe to
monitor peptide binding to amphiphilic aggregates. That conclusion is supported
by measurements with the peptide Abz-Leu-Arg-Phe-NH(2).
PMID- 17029729
TI - Self-assembly of melanin studied by laser light scattering.
AB - The unknown molecular weight and chemical structure of melanin place the study of
these pigments outside the range of the classical biochemical techniques; thus in
this paper the problem of characterizing these heterogeneous biopolymers was
approached by means of light scattering techniques, static and dynamic. The
static technique allowed us to identify the macromolecular properties (MW and
R(g)(2)(1/2)) of melanin extracted from sepia inksac and of two synthetic
analogues: L-Dopa melanin obtained by autooxidation and by enzymatic oxidation by
Tyrosinase. By dynamic light scattering (DLS), the hydrodynamic radius R(h) was
measured to monitor the temporal behaviour of the polymerization and aggregation
processes and R(h) variation by changing the chemical constraints of the
polymerization medium, such as pH and ionic strength. The fractal dimension d of
the aggregates of melanin, both natural and synthetic, in the past only
recognized during the aggregation of the synthetic one by lowering the pH of the
medium, was a useful parameter to further investigate and compare the structure
of melanin granules of differing origins, revealing for the natural sample, a
structure with clusters that are spherical, not largely hydrated and self
assembled, following a reaction limited aggregation kinetics (d=2.38).
PMID- 17029730
TI - Folding under inequilibrium conditions as a possible reason for partial
irreversibility of heat-denatured proteins: computer simulation study.
AB - Using computer simulations we have studied possible effects of heating and
cooling at different scan rates on unfolding and refolding of macromolecules. We
have shown that even the simplest two-state reversible transition can behave
irreversibly when an unfavorable combination of cooling rate, relaxation time and
activation energy of refolding occurs. On the basis of this finding we suppose
that apparent irreversibility of some proteins denatured by heat may result from
slow relaxation on cooling rather than thermodynamic instability and/or
irreversible alterations of the polypeptide chain. Using this kinetic reversible
two-state model, we estimated the effects of the scan rate and kinetic parameters
of the macromolecule on its unfolding-refolding process. A few recommendations
are suggested on how to reach maximal possible recovery after denaturation if
refolding appears to be under kinetic control.
PMID- 17029731
TI - The impact of abnormal autoimmune function on reproduction: maternal and fetal
consequences.
AB - The impact of abnormal autoimmune function on reproductive success has remained a
highly controversial issue. This is, at least partially, due to the relative lack
of demographic data from women with established autoimmune diseases. We,
therefore, investigated 163 women with proven autoimmune diseases and 73 controls
in a demographic study of reproductive success and impact of abnormal
autoimmunity on pregnancy and offspring. Women with autoimmune diseases
experienced fewer pregnancies overall (p=0.04) and fewer pregnancy losses
(p=0.05). Offspring from women with autoimmune diseases demonstrated a
significantly increased prevalence of confirmed autoimmune diseases (p=0.04; OR
3.759; 95%CL 1.04-1.27), which increased further if suspected, but not yet
confirmed, cases were added (p=0.001; OR 8.592; 95%CL 1.05-55.0). Women with
autoimmune diseases exhibited a trend towards lower cesarean section delivery
during their own birth and a significantly increased prevalence of disease in
vaginally delivered offspring (p=0.014; OR 6.041; 95%CL 1.32-38.22). Autoimmune
diseases impair female fecundity even before the diseases become clinically
overt. Offspring are at increased risk to develop autoimmune diseases, though
they may differ from those of their mothers. This risk appears to correlate with
mode of delivery and may be the consequence of varying cell traffic dynamics with
vaginal and cesarean section deliveries.
PMID- 17029732
TI - Flexibility of DNA in complex with proteins deduced from the distribution of
bending angles observed by scanning force microscopy.
AB - Flexibility and dynamics of DNA are important for DNA-binding and recognition by
proteins. Here the flexibility of DNA is calculated from the distribution of DNA
bending angles of single DNA molecules as observed by scanning force microscopy
by applying an equation that links the force constant of DNA-bending (f) to the
variance of the distribution of bending angles (sigma): f=RT/sigma(2). Using
published data, f is calculated to be 3-5 J/degree(2) for free DNA. Thus, bending
DNA by 20 degrees requires approx. 0.5-1 kJ/mol. This result shows that DNA is
very flexible and readily can be bent by thermal motion. DNA-flexibility is not
altered in some protein-DNA complexes (HhaI methyltransferase, EcoRV restriction
endonuclease). In contrast, DNA-binding by EcoRI endonuclease increases DNA
flexibility and binding by EcoRI methyltransferase restricts the flexibility of
DNA. During the transition of the RNA polymerase-sigma(54)-DNA complex from the
closed to the open form and of cro repressor from a non-specific to a specific
binding mode the flexibility of the DNA is strongly reduced.
PMID- 17029733
TI - Thermodynamics of aliphatic and aromatic hydrocarbons in water.
AB - Makhatadze and Privalov have analyzed the thermodynamics of transfer of aliphatic
and aromatic hydrocarbons from the gas phase into water. Finding that the
hydration free energy of aliphatic and aromatic hydrocarbons have different
signs, they conclude that the mechanism causing hydrophobicity of these solutes
is of a different nature. Here, we offer an alternative analysis of the
dissolution of these non-polar compounds into water based on a recently published
interpretation scheme for thermodynamic transfer functions. Our analysis shows
that the hydrophobicity of aromatic and aliphatic hydrocarbons is qualitatively
the same, i.e. its causes are the same namely the extremely high cohesive energy
of water which overcomes the favorable solute-solute and solute-water
interactions. However, both analyses conclude that the experimentally observed
quantitative difference between the interactions of water with aliphatic and
aromatic hydrocarbons, can be assigned to the formation of aromatic ring-water H
bonds.
PMID- 17029734
TI - TRP proteins and cancer.
AB - Cancer is the second most common cause of death in western countries. It is
therefore of fundamental importance to improve the treatment of patients with
malignant tumors. This goal can only be achieved if we get closer insight in the
various mechanisms leading to tumor formation. Significant progress in the
understanding of carcinogenesis has been made during the last couple of years.
Ion channels contribute to the regulation of cell proliferation which has
initially been shown for K+ channels. Meanwhile, other ion channels such as Cl-,
Na+ and Ca2+ channels seem to influence cellular function like growth, migration
and invasion. In addition, cation channels of the transient receptor potential
(TRP) superfamily are implicated in cancer formation. Most recent data concerning
TRP vanilloid (TRPV) type 6, TRP melastatin (TRPM) type 1 and 8 channels and
their relevance for common human cancer types will be highlighted in this review.
Furthermore, TRP channel structure and function will be discussed in the light of
their possible importance as prognostic markers and targets for drug discovery.
PMID- 17029735
TI - Differential activation of the JNK signal pathway by UV irradiation and glucose
deprivation.
AB - Exposure of mammalian cells to ultraviolet (UV) light or glucose deprivation
activates c-Jun NH2-terminal protein kinase (JNK). However, the exact mechanism
by which UV induces JNK activation is not yet understood completely. Previously,
we have observed that glucose deprivation activates the ASK1-SEK1-JNK signal
transduction pathway. In the present study, we reveal that UVC irradiation
induced JNK activation has a different signal transduction pathway from glucose
deprivation. UVC irradiation increases the interaction between JIP3 and MEKK1,
SEK1, while glucose deprivation increases the interaction between JIP3 and ASK1,
SEK1, and JNK. UVC irradiation activates MEKK1 rather than ASK1. We also observed
that MEKK1 interacted with Grb2 and Grb2-MEKK1 complex was recruited to epidermal
growth factor receptor (EGFR) after UVC irradiation. Taken together, our data
demonstrate that UVC-induced JNK activation adopts a different signaling cascade
(EGFR-Grb2-MEKK1-SEK1-JNK) from glucose deprivation (ASK1-SEK1-JNK).
PMID- 17029736
TI - Medical countermeasures to WMDs: defence research for civilian and military use.
AB - This document will address the contributions of defence research to both military
and civilian applications. Compared to civilian research capabilities,
particularly in terms of personnel, defence research resources are limited.
Additionally, many of the research targets are either classified or involve
applications that have (or had) limited civilian use. Recently, however, spurred
by counter-terrorism preparedness particularly in North America, many previously
'orphaned' research projects have assumed much greater prominence. This has
occurred in all areas of militarily significant research, but this paper will
focus on medical countermeasures to weapons of mass destruction and to a lesser
extent on detection/identification issues. In the area of countermeasures to
chemical weapons, most of the defence research has been devoted to "classical"
CWAs such as nerve agents, vesicants, choking and blood agents, with considerable
success in some applications. Similarly vaccination programs for the biological
weapons have also been quite successful. And recent attention has been directed
toward the "emerging" threats such as some of the exquisitely lethal toxins. The
difference now is that all of these research programs have the objective of
moving from research to development of not only military but also civilian use
very much sooner than later.
PMID- 17029737
TI - Determination of protein association constants by electrophoresis.
AB - An electrophoresis cell with scanning UV-absorption optics is presented. It
allows the measurement of moving reaction boundaries of dilute protein solutions
with a high-resolution. The protein profiles in the boundaries can be
extrapolated to infinite time after an appropriate transformation of space and
time coordinates and then evaluated with respect to association constants. This
is demonstrated for the dimer-tetramer equilibrium of haemoglobin.
PMID- 17029738
TI - Solvent isotope effect on thermodynamics of hydration.
AB - Partial molar heat capacities of five linear alcohols (methanol, ethanol, n
propanol, n-butanol, n-pentanol) and five N-substituted amides (n-propionamide, N
methylformamide, N-methylacetamide, N-methylpropionamide, N-ethylacetamide) in
aqueous D(2)O solution have been measured at 25 degrees C. The heat capacities of
transfer of these compounds from H(2)O to D(2)O were calculated using previously
reported (Makhatadze et al., Biophys. Chem. 64 (1997) 93) values of partial heat
capacities of alcohols and amides in aqueous H(2)O solutions. It is shown that
the sign and magnitude of the heat capacity change upon transfer from H(2)O to
D(2)O depends on the relative amount of polar and non-polar solvent accessible
surface areas of solute. Analysis shows that transfer of non-polar surface from
H(2)O to D(2)O is accompanied by a positive heat capacity change. In contrast,
transfer of polar surface from H(2)O to D(2)O occurs with negative heat capacity
change. Estimates show that the solvent isotope effect on the heat capacity
changes upon protein unfolding can be predicted using the changes of the polar
and non-polar surface area changes upon protein unfolding and the transfer data
of model compounds. Analysis of the thermodynamic functions of transfer of non
polar compounds from H(2)O to D(2)O shows puzzling behavior which contradicts
current definitions of the hydrophobic effect.
PMID- 17029739
TI - Bead modeling using HYDRO and SOLPRO of the conformation of multisubunit
proteins: sunflower and rape-seed 11S globulins.
AB - Oil seed globulins from sunflower and rape seed are multi-subunit, oligomeric
proteins whose native 11S form is a hexamer. In this work we try to determine the
spatial structure in which the six subunits of 11S globulin are arranged.
Experimental values of solution properties, including radius of gyration,
sedimentation and diffusion coefficients and intrinsic viscosity, are compared
with theoretical predictions for hexamers of various geometries. Bead model
calculations of solution properties are carried out using the HYDRO and SOLPRO
computer programs. A most compact shape, the regular octahedron, is the hexameric
structure that fits best the experimental values.
PMID- 17029740
TI - The 'Janus' nature of proteins: systems at the verge of the microscopic and
macroscopic world.
AB - Direct measurement of the heat capacity of proteins by microcalorimetry has had a
decisive impact on understanding the behaviour of these biopolymers. Statistical
mechanics allow a straightforward calculation and prediction of the enthalpy and
heat capacity curves from the partition function. We show that these predictions
can differ from the more intuitive models used so far for the description of the
thermodynamic behaviour of proteins if the transition involves a stoichiometry
other than 1:1. Furthermore, we delineate that the characteristics of protein
unfolding are governed by the fluctuations associated with the small size of
these molecules. Therefore it may be necessary to modify the picture of the
unfolding of small proteins in the light of statistical physics, while for very
large proteins the current view may be maintained as a useful limiting
approximation.
PMID- 17029741
TI - Effect of levetiracetam on visual-spatial memory following status epilepticus.
AB - Status epilepticus (SE) is often followed by severe cognitive impairment,
including memory impairment. Previous studies have shown that SE is associated
with impairment of single cells in the hippocampus that fire action potentials
when the animal is in a specific location in space, the so-called place cells,
and that place cell function correlates well with performance in tasks of visual
spatial memory. Place cell patterns therefore appear to be an excellent measure
of spatial memory and may serve as a tool to assess seizure-induced impairment in
memory. In this study we determined the relationship between visual-spatial
memory and place cell function following SE. In addition, we determined if
levetiracetam (LEV), an antiepileptic drug with a novel mechanism of action, can
improve cognitive function and place cell firing patterns when administered
following SE. SE was induced in adult male rats which were then randomized to
post-SE treatment with LEV or normal saline (NS) treatment for 14 days. Non-SE
control rats also were randomized to LEV or NS. Following discontinuation of LEV
rats were tested for visual-spatial memory in the Morris water-maze and then
underwent unit recording in the CA1 region of the hippocampus. Brains were then
evaluated for cell loss and mossy fiber sprouting. SE was associated with
severely impaired performance in the water-maze with SE rats demonstrating no
learning over four days of testing. Paralleling this memory deficit was a marked
disturbance in firing patterns of pyramidal neurons in CA1. Non-SE rats learned
quickly over four days of water-maze testing and had normal pyramidal cell firing
patterns. LEV had no major effects on water-maze performance or place cell
function. Histopathological examination of the brains showed severe cell loss in
CA1 in all of the SE rats with lesser degrees of injury in CA3 and the hilus. LEV
treatment resulted in less histological damage in the hippocampus but had no
effect on visual-spatial function or place cell physiology in either control or
SE rats.
PMID- 17029742
TI - Characterisation of the fibrinogenolytic properties of the buccal gland secretion
from Lampetra japonica.
AB - Lampetra japonica is representative of the ancient cyclostomota class of animals,
and its buccal gland secretion (called lamphredin) is known to act as an
anticoagulant. In this study, it was observed by both native-PAGE and SDS-PAGE
that the secretion mainly contained two protein bands, buccal gland secretion
protein-1 (BGSP-1, 159,909 Da) and buccal gland secretion protein-2 (BGSP-2,
25,660 Da). The N-terminal amino acids of BGSP-1 (EAESF QNLKT RICGG LNGLG) and
BGSP-2 (TSVND WKLLD TKLSA NRKVI) were sequenced. Using a Sephadex G-75 column, we
isolated BGSP-1, BGSP-2 and small peptides from the buccal gland secretion, but
found only BGSP-1 showed fibrinogenolytic activity. BGSP-1 and lamphredin were
found to rapidly degrade the alpha chain of human fibrinogen, slowly degrade the
beta chain and hardly degrade the gamma chain. BGSP-1 and lamphredin showed a
similar map by SDS-PAGE for the degradation of fibrinogen by cleavage at Ala(10)
Glu(11) and His(368)-Ser(369). BGSP-1 was also found to hydrolyze neuronal
protein tau at Glu(12)-Asp(13) and Gln(244)-Thr(245). Further study showed that
lamphredin and BGSP-1 were inactivated in the presence of a metal chelating agent
EDTA. However, addition of Ca(2+) or Mg(2+) but not Zn(2+) restored the
fibrinogenolytic activity. This suggests that BGSP-1 acts in the buccal gland as
a metalloproteinase with a broad substrate specificity. Furthermore, the
secretion showed cytolytic properties towards human SH-SY5Y and HeLa cells in
culture, and lamphredin at a 50-fold dilution induced cell death.
PMID- 17029743
TI - Purification and functional characterization of AAV1, a novel P-III
metalloproteinase, from Formosan Agkistrodon acutus venom.
AB - AAV1, an alkaline glycoprotein (GP), was purified from Agkistrodon acutus venom
by two chromatographic steps on successive DEAE-Sephadex A-50 and Superdex 75
FPLC columns. AAV1 on SDS-PAGE under non-reducing conditions migrated as a
monomeric and a polymeric forms with apparent molecular mass of 57 and 180 kDa,
respectively. Upon reduction, it appeared as a single broad band with a mass of
50.3 kDa corresponding to the size of a typical P-III metalloproteinase
acurhagin. The N-terminal sequence of an autoproteolytical 30 kDa-fragment of
AAV1 showed a high homology to that of venom proteins with Metalloproteinase,
Disintegrin-like, and Cysteine-rich (MDC) domains. Although it was devoid of
cleaving activity toward gelatin, fibronectin and prothrombin, AAV1
preferentially digested the Aalpha chain of fibrinogen and followed by the Bbeta
chain, leading to the inhibition of fibrinogen-induced platelet aggregation in
elastase-treated human platelets. However, the proteolytic activity of AAV1 was
completely inactivated by the chelating agent but not serine proteinase
inhibitor. Furthermore, AAV1 could concentration-dependently inhibit platelet
aggregation and suppress tyrosine phosphorylation of intracellular proteins in
collagen- and convulxin-stimulated platelets, respectively. The interaction of
MDC domains in AAV1 molecule with platelet GPVI was responsible for the
inhibitory effect of AAV1 on collagen- and convulxin-induced platelet
aggregation. Taken together, these pieces of evidence suggest that AAV1 from
Formosan viper venom belongs to a new member of high-molecular mass
metalloproteinase family and functions as a GPVI antagonist.
PMID- 17029745
TI - Experimental data and modelling of apparent molar volumes, isentropic
compressibilities and refractive indices in aqueous solutions of glycine + NaCl.
AB - Experiments have been performed at 298.15 K to measure the density, sound
velocity and refractive index of glycine in aqueous solutions of NaCl over a wide
range of both glycine and NaCl concentrations. The values of apparent molar
volume and isentropic compressibility of glycine were calculated from the
measured data. The results show a positive transfer volume of glycine from an
NaCl solution to a more concentrated NaCl solution. This indicates that the size
of a glycine molecule is larger in a solution with higher NaCl concentration. The
negative values of apparent isentropic compressibility imply that the water
molecules around the glycine molecules are less compressible than the water
molecules in the bulk solution. These effects are attributed to the doubly
charged behaviour of glycine and to the formation of physically bonded ion-pairs
between the charged groups of glycine and sodium and chloride ions. The formation
of ion-pairs, whose extents of binding reactions depend on the concentrations of
both NaCl and glycine, alter the hydration number of glycine. This also explains
the reason for the increase in the size of glycine with an increase in the NaCl
concentration. A model based on the Pitzer formalism has been developed to
correlate the activity coefficient, apparent molar volume and isentropic
compressibility of glycine in aqueous solutions of NaCl. The results show that
the model can accurately correlate the interactions in aqueous solutions of
glycine and NaCl.
PMID- 17029744
TI - Equilibrium unfolding of DLC8 monomer by urea and guanidine hydrochloride:
Distinctive global and residue level features.
AB - We present circular dichroism (CD), steady state fluorescence and
multidimensional NMR investigations on the equilibrium unfolding of monomeric
dynein light chain protein (DLC8) by urea and guanidine hydrochloride (GdnHCl).
Quantitative analysis of the CD and fluorescence denaturation curves reveals that
urea unfolding is a two-state process, whereas guanidine unfolding is more
complex. NMR investigations in the native state and in the near native states
created by low denaturant concentrations enabled residue level characterization
of the early structural and dynamic perturbations by the two denaturants.
Firstly, (15)N transverse relaxation rates in the native state indicate that the
regions around N10, Q27, the loop between beta2 and beta4 strands, and K87 at the
C-terminal are potential unfolding initiation sites in the protein. Amide and
(15)N chemical shift perturbations indicate different accessibilities of the
residues along the chain and help identify locations of the early perturbations
by the two denaturants. Guanidine and urea are seen to interact at several sites
some of which are different in the two cases. Notable among the common
interaction site is that around K87 which is in close proximity to W54 on the
protein structure, but the interaction modes of the two denaturants are
different. The secondary chemical shifts indicate that the structural
perturbation by 1M urea is small, compared to that by guanidine which is more
encompassing over the length of the chain. The probable (phi, psi) changes at the
individual residues have been calculated using the TALOS algorithm. It appears
that the helices in the protein are significantly perturbed by guanidine.
Further, comparison of the spectral density functions of the native and the two
near native states in the two denaturants implicate greater loosening of the
structure by guanidine as compared to that by urea, even though the structures
are still in the native state ensemble. These differences in the early
perturbations of the native state structure and dynamics by the two denaturants
might direct the protein along different pathways, as the unfolding progresses on
further increasing the denaturant concentration.
PMID- 17029746
TI - Coexistence of multiple propagating wave-fronts in a regulated enzyme reaction
model: link with birhythmicity and multi-threshold excitability.
AB - We analyze the spatial propagation of wave-fronts in a biochemical model for a
product-activated enzyme reaction with non-linear recycling of product into
substrate. This model was previously studied as a prototype for the coexistence
of two distinct types of periodic oscillations (birhythmicity). The system is
initially in a stable steady state characterized by the property of multi
threshold excitability, by which it is capable of amplifying in a pulsatory
manner perturbations exceeding two distinct thresholds. In such conditions, when
the effect of diffusion is taken into account, two distinct wave-fronts are shown
to propagate in space, with distinct amplitudes and velocities, for the same set
of parameter values, depending on the magnitude of the initial perturbation. Such
a multiplicity of propagating wave-fronts represents a new type of coexistence of
multiple modes of dynamic behavior, besides the coexistence involving, under
spatially homogeneous conditions, multiple steady states, multiple periodic
regimes, or a combination of steady and periodic regimes.
PMID- 17029747
TI - Magnetic field perturbations as a tool for controlling enzyme-regulated and
oscillatory biochemical reactions.
AB - The feasibility of magnetic field perturbations as a tool for controlling enzyme
regulated and oscillatory biochemical reactions is studied. Our approach is based
on recent experimental results that revealed magnetic field effects on the in
vitro activity of enzyme systems in accordance with the radical pair mechanism. A
minimum model consisting of two coupled enzyme-regulated reactions is discussed
that combines, in a self-consistent manner, magnetic field-sensitive enzyme
kinetics with non-linear dynamical principles. Furthermore, a simple detector
mechanism is described that is capable of responding to an oscillatory input.
Results reveal that moderate-strength magnetic fields (B=1-100 mT) may
effectively alter the dynamics of the system. In particular, a response behavior
is observed that depends on: (1) the combination of static and time-varying
magnetic fields; (2) the field amplitude; and (3) the field frequency in a non
linear fashion. The specific response behavior is critically determined by the
biochemical boundary conditions as defined by the kinetic properties of the
system. We propose an experimental implementation of the results based on the
oscillatory peroxidase-oxidase reaction controlled by the enzyme horseradish
peroxidase.
PMID- 17029748
TI - Intermembrane distance in multilamellar vesicles of phosphatidylcholine depends
on the interaction free energy between solvents and the hydrophilic segments of
the membrane surface.
AB - To investigate the interaction of the surface of biomembranes with solvents
systematically, we have studied the structure and phase behavior of multilamellar
vesicles of dipalmitoylphosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoyl
phosphatidylcholine (POPC) in dimethylformamide (DMF)-water mixture by X-ray
diffraction and differential scanning calorimetry. The solubility of
phosphorylcholine, which is the same molecular structure as the head-group of
phosphatidylcholine (PC), decreased with an increase in DMF concentration. This
result indicates that DMF is a poor solvent for the hydrophilic segments of the
surface of the PC membrane, and interaction free energy of the hydrophilic
segments of the membrane surface with solvents increases with an increase in DMF
concentration. X-ray diffraction data indicated that DPPC-MLVs were in the
bilayer gel phase from 0 to 80% (v/v) DMF, and that the spacing (lamellar repeat
period) and intermembrane distance of DPPC-MLV decreased with an increase in DMF
concentration. Main transition temperature and pre-transition temperature of DPPC
MLV increased with an increase in DMF concentration, and above 50% (v/v) DMF
there was no pre-transition. In the interaction of POPC-MLV with DMF, X-ray
diffraction data indicated that POPC-MLVs were in L(alpha) phase (liquid
crystalline phase) from 0 to 80% (v/v) DMF, and that the spacing and
intermembrane distance of POPC-MLV decreased with an increase in DMF
concentration. These results are discussed by the change of the interaction free
energy between the hydrophilic segments of the membrane surface and solvents. As
DMF concentration increases, this interaction free energy may increase, resulting
in the decrease of the intermembrane distance of PC-MLVs.
PMID- 17029749
TI - The relationship between performance and fMRI signal during working memory in
patients with schizophrenia, unaffected co-twins, and control subjects.
AB - While behavioral research shows working memory impairments in schizophrenics and
their relatives, functional neuroimaging studies of patients and healthy controls
show conflicting findings of hypo- and hyperactivation, possibly indicating
different relationships between physiological activity and performance. In a
between-subjects regression analysis of fMRI activation and performance, low
performance was associated with relatively lower activation in patients than
controls, while higher performance was associated with higher activation in
patients than controls in DLPFC and parietal cortex, but not occipital cortex,
with unaffected twins of schizophrenics being intermediate between the groups.
Accordingly, this supports the idea that both hyper and hypoactivation may be
possible along a continuum of behavioral performance in a way consistent with a
neural inefficiency model. Further, this study offers preliminary evidence that
the relationship between behavior and physiology in schizophrenia may be
heritable.
PMID- 17029750
TI - The lymphotoxin Cys13Arg polymorphism and cognitive functioning in individuals
with schizophrenia.
AB - Genetic factors that modulate the immune response have been implicated as risk
factors for schizophrenia and cognitive impairment. We assessed the correlation
between cognitive functioning and the LTA Cys13Arg polymorphism in 351
individuals with schizophrenia, 122 with bipolar disorder, and 160 controls.
There was a significant association between cognitive functioning and the LTA
Cys13Arg polymorphism within the schizophrenia (p<0.008) but not the other
diagnostic groups. There was no association between cognitive functioning and the
two other polymorphisms in the same gene complex. The LTA Cys13Arg polymorphism
may represent a risk factor for cognitive impairment in individuals with
schizophrenia.
PMID- 17029752
TI - PSA-NCAM in mammalian structural plasticity and neurogenesis.
AB - Polysialic acid (PSA) is a linear homopolymer of alpha2-8-N acetylneuraminic acid
whose major carrier in vertebrates is the neural cell adhesion molecule (NCAM).
PSA serves as a potent negative regulator of cell interactions via its unusual
biophysical properties. PSA on NCAM is developmentally regulated thus playing a
prominent role in different forms of neural plasticity spanning from embryonic to
adult nervous system, including axonal growth, outgrowth and fasciculation, cell
migration, synaptic plasticity, activity-induced plasticity, neuronal-glial
plasticity, embryonic and adult neurogenesis. The cellular distribution,
developmental changes and possible function(s) of PSA-NCAM in the central nervous
system of mammals here are reviewed, along with recent findings and theories
about the relationships between NCAM protein and PSA as well as the role of
different polysialyltransferases. Particular attention is focused on
postnatal/adult neurogenesis, an issue which has been deeply investigated in the
last decade as an example of persisting structural plasticity with potential
implications for brain repair strategies. Adult neurogenic sites, although
harbouring all subsequent steps of cell differentiation, from stem cell division
to cell replacement, do not faithfully recapitulate development. After birth,
they undergo morphological and molecular modifications allowing structural
plasticity to adapt to the non-permissive environment of the mature nervous
tissue, that are paralled by changes in the expression of PSA-NCAM. The use of
PSA-NCAM as a marker for exploring differences in structural plasticity and
neurogenesis among mammalian species is also discussed.
PMID- 17029751
TI - Insulin resistance index and counter-regulatory factors during olanzapine or
risperidone administration in subjects with schizophrenia.
PMID- 17029753
TI - Fate of transplanted nail matrical cells and potential of hard keratin production
in vivo.
PMID- 17029754
TI - The role of Pipelle Mark II sampling in endometrial disease diagnosis.
AB - OBJECTIVE: To evaluate the feasibility and accuracy of Pipelle Mark II sampling
(designed for combined cytology and histology testing) in the diagnosis of
endometrial disease. MATERIALS AND METHODS: A 97 women with abnormal uterine
bleeding or intrauterine lesions on ultrasound examination underwent Pipelle Mark
II endometrial sampling, followed by diagnostic hysteroscopy. The adequacy of
endometrial samples obtained for cytological and histological analysis was
assessed. A correlation was established between endometrial cytology, histology
and diagnostic hysteroscopy results. Where discrepancies were found, they were
compared with the histological results obtained from operative hysteroscopy.
RESULTS: The tissue samples obtained for cytological and histological diagnoses
were insufficient in 14.4% and 11.3% of patients, respectively. The opposite was
found in the group of postmenopausal women (N=52): the tissue samples for
cytological and histological diagnoses were insufficient in only 3.8% and 15.4%
of cases, respectively. The cytological results corroborated diagnostic
hysteroscopy findings and histological results in all cases but 3 (3.6%). Only
two cases of endometrial carcinoma were reported in this group of patients, and
they were both detected by all three methods. The rate of false positives with
endometrial cytological sampling was 3.6%. There were no false negatives.
CONCLUSION: Pipelle Mark II endometrial sampling is feasible. It provides
adequate samples for histological and/or cytological analysis and reliable
results. It reduces the rate of false negative results for endometrial cancer.
Pipelle Mark II sampling is particularly useful in postmenopausal women and in
women with endometrial atrophy. Other larger studies are necessary to evaluate
the efficiency of Pipelle Mark II.
PMID- 17029755
TI - Prenatal sonographic findings in 207 fetuses with trisomy 21.
AB - OBJECTIVE: The objective was to evaluate the contribution of second trimester
ultrasound examination to the prenatal diagnosis of trisomy 21 in 207 fetuses
with this aneuploidy. The type and frequency of abnormal sonographic findings
were determined. Possible multiple malformation patterns, characteristic of
trisomy 21 were sought. STUDY DESIGN: Singleton fetuses that had prenatal
sonography during the second trimester, then underwent cytogenetic evaluation in
our institution, made up the study population. The sonographic findings of 207
fetuses with trisomy 21 were analyzed. RESULTS: Between 1990 and 2004, fetal
karyotyping was performed in 22,150 patients for different indications. An
abnormal karyotype was diagnosed in 514 cases (2.3%); among them 207 fetuses with
trisomy 21 were detected (40.3%). Abnormal sonography was seen in 63.8% of the
cases. Structural anomalies were detected in 28.5% of the trisomy 21 fetuses,
among them cardiac defects (15.9%), central nervous system anomalies (14.5%), and
cystic hygromas (6.8%) were the most common. Of the minor markers, increased
nuchal translucency (28%), pyelectasis (20.3%), and shorter extremities (8.7%)
were common findings. CONCLUSIONS: Appropriate diagnosis of structural anomalies,
looking for relatively easily detectable minor markers and incorporating fetal
echocardiography into the second trimester sonographic protocol, may increase the
contribution of mid-trimester ultrasound examination to diagnosing trisomy 21.
PMID- 17029756
TI - Assessment of factors contributing to changes in the incidence of antimicrobial
drug resistance in Salmonella enterica serotypes Enteritidis and Typhimurium from
humans in England and Wales in 2000, 2002 and 2004.
AB - An investigation into changes in the occurrence of antimicrobial resistance in
Salmonella enterica serotypes Enteritidis and Typhimurium from human infection in
England and Wales in 2000, 2002 and 2004 has shown that the incidence of strains
of S. Enteritidis with resistance to nalidixic acid coupled with decreased
susceptibility to ciprofloxacin has more than doubled between 2000 and 2004,
whereas the overall levels of resistance in S. Typhimurium have fallen by ca.
25%. In relation to published data on veterinary sales of antimicrobials in the
UK, the findings demonstrate that changes in the incidence of resistance do not
correlate with changes in veterinary usage. For S. Enteritidis, important factors
in the increased incidence of resistance were foreign travel and the consumption
of imported foods contaminated with drug-resistant strains. For S. Typhimurium,
the most important factor has been an overall decline in the occurrence of
multiple drug-resistant S. Typhimurium definitive phage type 104. These studies
have demonstrated that changes in the incidence of resistance in predominant
salmonellas in humans in England and Wales from 2000 to 2004 are multifactorial.
The findings also demonstrate that, in order to combat drug resistance in
zoonotic salmonellas causing infections in humans, controls on the use of
antibiotics in food animals analogous to those in operation in the UK should be
implemented in countries that regularly import food into the UK.
PMID- 17029757
TI - Radiocaesium accumulation in stemwood: integrated approach at the scale of forest
stands for contaminated Scots pine in Belarus.
AB - Twenty years after the Chernobyl accident, root uptake from the surface layers of
contaminated forest soils plays a major role in radiocaesium ((137)Cs) transfer
to the trees and accumulation in perennial compartments, including stemwood.
Trustworthy long-term predictions (modelling) of stemwood contamination with
(137)Cs should accordingly be based on a reliable picture of this source-sink
relationship. Considering the complexity of the processes involved in (137)Cs
cycling in forest stands, elementary ratios like transfer factors (TF) were shown
to be not very relevant for that purpose. At the tree level, alternatives like
the wood immobilisation potential (WIP) have therefore been proposed in order to
quantify the current net (137)Cs accumulation in stemwood. Our objective was here
to compare WIP values determined for a series of contaminated forest stands in
Belarus with the corresponding pools of (137)Cs available in the soil for root
uptake. The comparison reveals that both indices are quite proportional, whatever
the forest ecosystem features. This corroborates the relevancy of WIP as an
indicator of the current (137)Cs root uptake by the trees, which could
accordingly help to improve the existing models of (137)Cs cycling and the long
term management of contaminated forest ecosystems.
PMID- 17029758
TI - Development and application of a GIS-based sediment budget model.
AB - Accelerated erosion and increased sediment yields resulting from changes in land
use are a critical environmental problem. Resource managers and decision makers
need spatially explicit tools to help them predict the changes in sediment
production and delivery due to unpaved roads and other types of land disturbance.
This is a particularly important issue in much of the Caribbean because of the
rapid pace of development and potential damage to nearshore coral reef
communities. The specific objectives of this study were to: (1) develop a GIS
based sediment budget model; (2) use the model to evaluate the effects of unpaved
roads on sediment delivery rates in three watersheds on St. John in the US Virgin
Islands; and (3) compare the predicted sediment yields to pre-existing data. The
St. John Erosion Model (STJ-EROS) is an ArcInfo-based program that uses empirical
sediment production functions and delivery ratios to quantify watershed-scale
sediment yields. The program consists of six input routines and five routines to
calculate sediment production and delivery. The input routines have interfaces
that allow the user to adjust the key variables that control sediment production
and delivery. The other five routines use pre-set erosion rate constants, user
defined variables, and values from nine data layers to calculate watershed-scale
sediment yields from unpaved road travelways, road cutslopes, streambanks,
treethrow, and undisturbed hillslopes. STJ-EROS was applied to three basins on
St. John with varying levels of development. Predicted sediment yields under
natural conditions ranged from 2 to 7Mgkm(-2)yr(-1), while yield rates for
current conditions ranged from 8 to 46Mgkm(-2)yr(-1). Unpaved roads are estimated
to be increasing sediment delivery rates by 3-6 times for Lameshur Bay, 5-9 times
for Fish Bay, and 4-8 times for Cinnamon Bay. Predicted basin-scale sediment
yields for both undisturbed and current conditions are within the range of
measured sediment yields and bay sedimentation rates. The structure and user
interfaces in STJ-EROS mean that the model can be readily adapted to other areas
and used to assess the impact of unpaved roads and other land uses sediment
production and delivery.
PMID- 17029759
TI - Collaborative environmental planning in river management: an application of
multicriteria decision analysis in the White River Watershed in Vermont.
AB - Multicriteria decision analysis (MCDA) provides a well-established family of
decision tools to aid stakeholder groups in arriving at collective decisions.
MCDA can also function as a framework for the social learning process, serving as
an educational aid in decision problems characterized by a high level of public
participation. In this paper, the framework and results of a structured decision
process using the outranking MCDA methodology preference ranking organization
method of enrichment evaluation (PROMETHEE) are presented. PROMETHEE is used to
frame multi-stakeholder discussions of river management alternatives for the
Upper White River of Central Vermont, in the northeastern United States.
Stakeholders met over 10 months to create a shared vision of an ideal river and
its services to communities, develop a list of criteria by which to evaluate
river management alternatives, and elicit preferences to rank and compare
individual and group preferences. The MCDA procedure helped to frame a group
process that made stakeholder preferences explicit and substantive discussions
about long-term river management possible.
PMID- 17029760
TI - An analysis of functional neuroimaging studies of dorsolateral prefrontal
cortical activity in depression.
AB - Repetitive transcranial magnetic stimulation (rTMS) is currently undergoing
active investigation for use in the treatment of major depression. Recent
research has indicated that current methods used to localize the site of
stimulation in dorsolateral prefrontal cortex (DLPFC) are significantly
inaccurate. However, little information is available on which to base a choice of
stimulation site. The aim of the current study was to systematically examine
imaging studies in depression to attempt to identify whether there is a pattern
of imaging results that suggests an optimal site of stimulation localization. We
analysed all imaging studies published prior to 2005 that examined patients with
major depression. Studies reporting activation in DLPFC were identified. The
DLPFC regions identified in these studies were analysed using the Talairach and
Rajkowska-Goldman-Rakic coordinate systems. In addition, we conducted a
quantitative meta-analysis of resting studies and studies of serotonin reuptake
inhibitor antidepressant treatment. There was considerable heterogeneity in the
results between studies. Changes in Brodmann area 9 were relatively consistently
identified in resting, cognitive activation and treatment studies included in the
meta-analysis. However, there was little consistency in the direction of these
changes or the hemisphere in which they were identified. At this stage, the
results of imaging studies published to date have limited capacity to inform the
choice of optimal prefrontal cortical region for the use in rTMS treatment
studies.
PMID- 17029761
TI - Adsorption behaviour and surfactant elution of cationic salivary proteins at
solid/liquid interfaces, studied by in situ ellipsometry.
AB - Adsorption of the cationic salivary proteins lactoferrin, lactoperoxidase,
lysozyme and histatin 5 to pure (hydrophilic) and methylated (hydrophobized)
silica surfaces was investigated by in situ ellipsometry. Effects of
concentration (=10 microgml(-1), for lysozyme =200 microgml(-1)) and
dependence of surface wettability, as well as adsorption kinetics and elutability
of adsorbed films by buffer and sodium dodecyl sulphate (SDS) solutions were
investigated. Results showed that the amounts adsorbed decreased in the order
lactoferrin>/=lactoperoxidase>lysozyme>/=histatin 5. On hydrophilic silica, the
adsorption was most likely driven by electrostatic interactions, which resulted
in adsorbed amounts of lactoferrin that indicated the formation of a monolayer
with both side-on and end-on adsorbed molecules. For lactoperoxidase the adsorbed
amounts were somewhat higher than an end-on monolayer, lysozyme adsorption showed
amounts corresponding to a side-on monolayer, and histatin 5 displayed adsorbed
amounts in the range of a side-on monolayer. On hydrophobized substrata, the
adsorption was also mediated by hydrophobic interactions, which resulted in lower
adsorbed amounts of lactoferrin and lactoperoxidase; closer to side-on monolayer
coverage. For both lysozyme and histatin 5 the adsorbed amounts were the same as
on the hydrophilic silica. The investigated proteins exhibited fast adsorption
kinetics, and the initial kinetics indicated mass transport controlled behaviour
at low concentrations on both types of substrates. Buffer rinsing and SDS elution
indicated that the proteins in general were more tightly bound to the
hydrophobized surface compared to hydrophilic silica. Overall, the surface
activity of the investigated proteins implicates their importance in the salivary
film formation.
PMID- 17029762
TI - Light scattering in colloidal solution of magnetite in electric and magnetic
fields.
AB - Light scattering by magnetite particles in kerosene under the simultaneous action
of crossed electric and magnetic fields was studied. Decreasing of variation of
light scattering intensity at some values of electric and magnetic fields have
been found. Values of fields at which a minimum of light scattering intensity
occur depend on the angle between laser beam and the plane of crossed fields.
PMID- 17029763
TI - [Severe malaria: assessment of the treatment of anaemia and cerebral
manifestations in a tropical intensive cares unit].
PMID- 17029764
TI - Advanced fuzzy cellular neural network: application to CT liver images.
AB - OBJECTIVE: To achieve better boundary integrities and recall accuracies for
segmented liver images, use of the advanced fuzzy cellular neural network
(AFCNN), as a variant of the fuzzy cellular neural network (FCNN), is proposed to
effectively segment CT liver images. MATERIALS AND METHODS: In order to better
utilize relevant contour and gray information from liver images, we have improved
the FCNN [Wang S, Wang M. A new algorithm NDA based on fuzzy cellular neural
networks for white blood cell detection. IEEE Trans Inform Technol Biomed, in
press], which proved to be very effective for the segmentation of microscopic
white blood cell images, to create the novel neural network, AFCNN. Its
convergent property and global stability are proved. Based on the FCNN-based NDA
algorithm [Wang S, Wang M. A new algorithm NDA based on fuzzy cellular neural
networks for white blood cell detection. IEEE Trans Inform Technol Biomed, in
press], we developed the AFCNN-based NDA algorithm, which we used to segment 5 CT
liver images. For comparison, we also segmented the same 5 CT liver images using
the FCNN-based NDA algorithm. RESULTS AND CONCLUSION: : AFCNN has distinct
advantages over FCNN in both boundary integrity and recall accuracy. In
particular, the performance index Binary_rate is generally much higher for AFCNN
than for FCNN when applied to CT liver images.
PMID- 17029765
TI - Solving satisfiability problems using a novel microarray-based DNA computer.
AB - An algorithm based on a modified sticker model accompanied with an advanced MEMS
based microarray technology is demonstrated to solve SAT problem, which has long
served as a benchmark in DNA computing. Unlike conventional DNA computing
algorithms needing an initial data pool to cover correct and incorrect answers
and further executing a series of separation procedures to destroy the unwanted
ones, we built solutions in parts to satisfy one clause in one step, and
eventually solve the entire Boolean formula through steps. No time-consuming
sample preparation procedures and delicate sample applying equipment were
required for the computing process. Moreover, experimental results show the bound
DNA sequences can sustain the chemical solutions during computing processes such
that the proposed method shall be useful in dealing with large-scale problems.
PMID- 17029766
TI - Permeability of the reconstructed human epidermis model Episkin in comparison to
various human skin preparations.
AB - The objective of this work was to compare the barrier function of the small
diameter reconstructed human epidermis model Episkin (d=12 mm) to human skin in
vitro. For that purpose a modification for the Franz diffusion cell (d=15mm) had
to be developed so as to allow direct comparison with the following human skin
preparations: Full thickness skin (FTS), split thickness skin (STS), heat
separated epidermis (HSE), and trypsin isolated stratum corneum (TISC). Among the
tested preparations, HSE appeared to be the most preferable due to its clear
morphological structure and ease of preparation. The lipid profile of HSE and
Episkin was analyzed and showed significant differences in terms of cholesterol,
ceramides and triglycerides contents, whereas cholesterol esters and fatty acids
were not different. Permeation data with HSE and Episkin were then gathered using
caffeine and testosterone. Both test compounds permeated much faster through
Episkin than through HSE. Moreover, opposed to Episkin, HSE differentiated
between the two test compounds. In spite of the remarkable progress in developing
RHEs in the past years at this time Episkin can obviously not yet fully replace
human skin for in vitro permeability experiments.
PMID- 17029767
TI - Phenotypic characterisation of mice with exaggerated and missing LH/hCG action.
AB - In order to study the physiology and pathophysiology of gonadotrophin action, we
have produced transgenic (TG) mice overexpressing human chorionic gonadotrophin
(hCG) alpha and beta subunits (hCG+ mice) and knockout (KO) mice for the
luteinising hormone receptor (LHR; LuRKO mice). The two extremes in LH function,
i.e. strong LH/hCG stimulation and total blockade of this action, confirm
numerous earlier concepts about LH function, but they also reveal new aspects
about gonadal function during excessive LH production and in the absence of this
trophic stimulus. The purpose of this review is to summarise the key findings on
these two genetically modified mouse models.
PMID- 17029768
TI - 1alpha,25-dihydroxyvitamin D3 downregulates CYP27B1 and induces CYP24A1 in colon
cells.
AB - The antimitotic and prodifferentiating 1alpha,25-dihydroxyvitamin D3 (1alpha,25
(OH)2D3), synthesized at various extrarenal sites could potentially prevent
sporadic tumor development. Physiological regulation of extrarenal Vitamin D
hydroxylases following tissue accumulation of 1alpha,25-(OH)2D3 is unknown. We
therefore investigated basal and Vitamin D-regulated expression and activity of
the synthesizing (CYP27B1) and metabolizing (CYP24A1) hydroxylase in three cell
lines derived from the colon, and compared this to cells from the prostate and
mammary gland. Our results show that all cells, irrespective of origin and
differentiation, express CYP27B1 mRNA, whereas basal CYP24A1 mRNA is highly
expressed only in undifferentiated cells. Treatment with 1alpha,25-(OH)2D3
diminishes CYP27B1 and Vitamin D receptor mRNA expression, but elevates CYP24A1
mRNA to equal levels in all cells. As shown by HPLC, CYP27B1 is active only if
basal 24-hydroxylation is not maximally functional. In turn, accumulation of
1alpha,25-(OH)2D3 will induce 24-hydroxylation. We conclude that, although
extrarenal and renal metabolic pathways for Vitamin D are similar, malignancy of
tumor cells determines extent of Vitamin D catabolism.
PMID- 17029769
TI - Eosinophilic pleural effusion after gastric variceal obliteration with
cyanoacrylate.
AB - Pleuropulmonary complications after endoscopic injection sclerotherapy for
treatment of esophagogastric varices are not uncommon but are usually mild and
self-limited. Herein we report a male patient with liver cirrhosis who underwent
endoscopic injection sclerotherapy, using a mixture of n-butyl-2-cyanoacrylate
and ethiodized oil for obliteration of gastric varices. After the procedure, he
developed moderate amount of left pleural effusion that persisted for a period of
time and required thoracentesis and medical treatment. We believed that the
inadvertent retrograde reflux of the embolized glue and ethiodized oil via the
portosystemic venous collateral into the left pleura might be the possible
mechanism for the development of left pleural effusion as the droplets of
ethiodized oil were seen along the left pleura on the imaging studies.
PMID- 17029770
TI - Severe vocal cord dysfunction resistant to all current therapeutic interventions.
AB - Vocal cord dysfunction (VCD) is characterised by paradoxical vocal cord adduction
during inspiration or throughout the respiratory cycle, it results in wheeze,
stridor, cough and dyspnoea. Although asthma and VCD can coexist, patients with
VCD are frequently misdiagnosed with refractory asthma. It can severely restrict
an individual's level of activity and effective therapeutic control can be
difficult to achieve. We report the case of a patient who was treated with all
available therapeutic interventions, including intralaryngeal botulinum toxin
injection, but failure resulted in a permanent trachesotomy.
PMID- 17029771
TI - The effect of fresh frozen plasma in severe closed head injury.
AB - OBJECTIVE: Traumatic brain injury (TBI) is one of the most common causes of
morbidity and mortality. Coagulopathy, commonly occurring after severe TBI, is
associated with poor outcome and secondary complications, especially delayed
traumatic intracerebral hematoma (DTICH). In this study we evaluated the effect
of fresh frozen plasma (FFP) on the reduction in the incidence of DTICH in severe
closed head injury victims. METHODS: This study was carried out as a double-blind
randomized clinical trial. Ninety patients were entered in two parallel groups
taking either FFP or normal saline (N/S). Patients' selection criteria for both
groups were: severe closed head injury (Glasgow coma scale < or =8), no mass
lesion required evacuation and no history of coagulopathy. The clinical findings,
laboratory data, computed tomography (CT) scans and Glasgow outcome scale after 1
month were assessed and compared in two groups. RESULTS: Out of 90 patients, 44
received FFP and 46 received N/S. The development of new intracerebral hematoma
in follow-up CT scans were more common in the FFP group than the N/S group
(p=0.012). Both groups showed similar frequency of poor outcome (p=0.343). The
mortality was significantly more common in the FFP group than in the N/S group
(63% versus 35%, p=0.006). CONCLUSION: The result of this study revealed that
early empirical infusion of FFP in patients with severe head injury may lead to
adverse effects, such as an increase in the frequency of DTICH and an increase in
the mortality.
PMID- 17029774
TI - Aberrant methylation of the 8p22 tumor suppressor gene DLC1 in renal cell
carcinoma.
AB - Epigenetic mechanisms involving DNA methylation and chromatin remodeling are
important in silencing tumor suppressor genes (TSG) in various malignancies,
including renal cell carcinoma (RCC). DLC1 (deleted in liver cancer 1)/ARHGAP7 is
a recently identified 8p22 candidate TSG. Frequent methylation of the DLC1
promoter with resultant gene silencing has been reported in several tumors, but
not in RCC yet. We examined DLC1 promoter methylation in 34 primary RCCs and the
corresponding non-malignant tissues, and the correlation of DLC1 methylation with
the clinicopathological characteristics of RCC patients. Although DLC1
methylation and downregulation were only detected in one of seven RCC cell lines
using methylation-specific PCR (MSP) and semi-quantitative reverse-transcription
PCR, we found that the DLC1 promoter was methylated in 35% (12/34) of primary RCC
tumors, which was further confirmed by direct sequencing of MSP products and high
resolution bisulfite genomic sequencing. In contrast, only one of the 34 (3%) non
malignant renal tissues had weak methylation. Aberrant DLC1 methylation appeared
to be a relatively early event during renal tumorigenesis since 33% of the RCC
tumors with pT1 (TNM staging) showed methylation, which is similar to other late
stage tumors. Thus, our results demonstrated that DLC1 methylation occurs in a
subset of RCC tumors and may play a role in renal carcinogenesis.
PMID- 17029773
TI - The E705K mutation in hPMS2 exerts recessive, not dominant, effects on mismatch
repair.
AB - The hPMS2 mutation E705K is associated with Turcot syndrome. To elucidate the
pathogenesis of hPMS2-E705K, we modeled this mutation in yeast and characterized
its expression and effects on mutation avoidance in mammalian cells. We found
that while hPMS2-E705K (pms1-E738K in yeast) did not significantly affect hPMS2
(Pms1p in yeast) stability or interaction with MLH1, it could not complement the
mutator phenotype in MMR-deficient mouse or yeast cells. Furthermore, hPMS2
E705K/pms1-E738K inhibited MMR in wild-type (WT) mammalian cell extracts or yeast
cells only when present in excess amounts relative to WT PMS2. Our results
strongly suggest that hPMS2-E705K is a recessive loss-of-function allele.
PMID- 17029775
TI - Adsorption of malachite green on groundnut shell waste based powdered activated
carbon.
AB - In the present technologically fast changing situation related to waste
management practices, it is desirable that disposal of plant waste should be done
in a scientific manner by keeping in view economic and pollution considerations.
This is only possible when the plant waste has the potential to be used as raw
material for some useful product. In the present study, groundnut shell, an
agricultural waste, was used for the preparation of an adsorbent by chemical
activation using ZnCl2 under optimized conditions and its comparative
characterisation was conducted with commercially available powdered activated
carbon (CPAC) for its physical, chemical and adsorption properties. The groundnut
shell based powdered activated carbon (GSPAC) has a higher surface area, iodine
and methylene blue number compared to CPAC. Both of the carbons were used for the
removal of malachite green dye from aqueous solution and the effect of various
operating variables, viz. adsorbent dose (0.1-1 g l(-1)), contact time (5-120
min) and adsorbate concentrations (100-200 mg l(-1)) on the removal of dye, has
been studied. The experimental results indicate that at a dose of 0.5 g l(-1) and
initial concentration of 100 mg l(-1), GSPAC showed 94.5% removal of the dye in
30 min equilibrium time, while CPAC removed 96% of the dye in 15 min. The
experimental isotherm data were analyzed using the linearized forms of
Freundlich, Langmuir and BET equations to determine maximum adsorptive
capacities. The equilibrium data fit well to the Freundlich isotherm, although
the BET isotherm also showed higher correlation for both of the carbons. The
results of comparative adsorption capacity of both carbons indicate that
groundnut shell can be used as a low-cost alternative to commercial powdered
activated carbon in aqueous solution for dye removal.
PMID- 17029776
TI - Bioremediation of polycyclic aromatic hydrocarbons (PAHs)-contaminated sewage
sludge by different composting processes.
AB - The efficiency of four different composting processes to bioremediate polycyclic
aromatic hydrocarbons (PAHs)-contaminated sewage sludge was investigated. Prior
to composting, sewage sludge coming from the Datansha wastewater treatment plant,
Guangzhou, China, was mixed with rice straw to obtain a C/N ratio of 13:1. After
56 days of composting, the total concentrations of 16 PAHs (Sigma(PAHs)) ranged
from 1.8 to 10.2 mg kg(-1) dry weight, decreasing in order of inoculated-manual
turned compost (IMTC)>manual turned compost (MTC)>continuous aerated compost
(CAC)>intermittent aerated compost (IAC), exhibiting removal rates of 64%, 70%,
85% and 94%, respectively. Individual PAHs were generally removed in similar
rates. IAC treatment showed a higher removal rate of high molecular weight PAHs
and carcinogenic PAHs comparing to the other composting processes.
PMID- 17029777
TI - Dehydrogenase based reagentless biosensor for monitoring phenylketonuria.
AB - Phenylketonuria (PKU) is a disease characterized by an inability to metabolize
the amino acid l-phenylalanine. The resulting buildup leads to brain damage and
ultimately mental retardation in children if their phenylalanine intake is not
carefully controlled. The National Institutes of Health recently suggested that
people with PKU monitor their phenylalanine levels throughout their life and be
put on a low phenylalanine diet. As an alternative approach to analysis using
blood, this paper describes the first reagentless dehydrogenase based sensor for
the determination of phenylalanine in human urine. The clinical range of
phenylalanine in human urine is 20-60mM for people with PKU. Although most
clinical analysis is performed using blood, urine was chosen due to its high
concentrations of phenylalanine in phenylketonurics, as well as its simple, safe,
and painless collection. The sensor is comprised of a carbon paste electrode with
nicotinamide adenine dinucleotide (NAD(+)), phenylalanine dehydrogenase (PDH),
uricase, and an electron mediator, 3,4-dihydroxybenzaldehyde (3,4-DHB), all mixed
into the paste. The electron mediator reacts with the electrode surface to
produce two redox species, which catalytically oxidize NADH. The behavior of the
electron mediator mixed into a carbon paste electrode has not been previously
investigated. Cyclic voltammetry was used to characterize the sensor's response
to NADH, and with the addition of PDH and NAD(+) to the paste, its response to
phenylalanine in human urine. The limit of detection for phenylalanine is 0.5mM
(S/N=3).
PMID- 17029778
TI - Electrochemical studies on horseradish peroxidase covalently coupled with redox
dyes.
AB - The present study aims at investigating the use of redox dyes as non-diffusional
electron mediators in hydrogen peroxide biosensors using horseradish peroxidase
(HRP). We observe that the two redox dyes Safranine O and Neutral Red covalently
bound to HRP, efficiently mediate electron transfer from the active site of the
enzyme to the electrode surface. Dyes bound to the enzyme using a spacer arm
diaminohexane further enhance the electron transfer. The enzyme electrodes show a
linear response to the concentration of H2O2 up to 500 microM concentration and
with a detection limit of around 50 microM. The dyes can be used as coupled
mediators to develop a successful electro-optical biosensor.
PMID- 17029779
TI - Electrochemical detection of HbA1c, a marker [correction of maker] for diabetes,
using a flow immunoassay system.
AB - An on-chip electrochemical flow immunoassay system for the detection of
hemoglobin A1c (HbA1c) was developed using anti-human hemoglobin (Hb) IgG labeled
with ferrocene monocarboxylic acid (Fc-COOH) and boronate-affinity
chromatography. An on-chip column packed with boronate-activated agarose beads
was used for the separation of HbA1c from both non-glycated Hb and free antibody.
Anti-human Hb IgG conjugated to Fc-COOH (Fc-IgG) was used for the electrochemical
detection of HbA1c. The assay procedure included immunoreactions with Fc-IgG and
HbA1c, separation of immunocomplexes by boronate affinity, and electrochemical
detection of Fc-IgG-HbA1c immunocomplexes. The immunoreaction mixtures were
injected onto a boronate-affinity column. HbA1c-antibody complexes were then
trapped onto the column by the affinity of HbA1c to boronic acid. Subsequently,
elution buffer containing sorbitol was applied to elute HbA1c-antibody complexes
and a current was detected by applying 600 mV versus Ag/AgCl. The elution signal
was an estimation of the HbA1c amount. A linear correlation between the increase
of current and HbA1c concentration was obtained up to an HbA1c concentration of
500 microg/ml. The HbA1c flow immunoassay was successfully achieved using
hemolysates. This electrochemical flow immunoassay system enabled us to construct
a novel point-of-care testing device for the monitoring of glycated proteins
including HbA1c.
PMID- 17029780
TI - Immunomagnetic separation and MS/SPR end-detection combined procedure for rapid
detection of Staphylococcus aureus and protein A.
AB - The aim of this study was to establish an IMS-MS/SPR technique for the detection
of Staphylococcus aureus (S. aureus) and Staphylococcus protein A (SPA) at the
same time, which consists of isolating S. aureus and trapping-enrichmenting its
SPA by IMS, and the end point is determined by using either MS or SPR
measurements. Magnetic bead (MB) containing aldehyde group was synthesized with
latex-polymerization and immunomagnetic bead (IMB) was fabricated by modifying
its surface with an oriented layer of human IgG in covalent linkage. As soon as
sample of pulverator-treated bacterial cell lysate (10(8) cfu/mL) was incubated
with IMB at 4 degrees C for 30 min, SPA was captured and separated from the mixed
solution in a few minutes by the IMB and then detected with mass spectrometry
after washing. SPR was used to detect S. aureus quantitatively in situ at the end
detection procedure. All in all, this technique can be employed to detect rapidly
SPA and S. aureus within 2h and also be applied to detect other cells or their
membrane proteins with changed modified antibodies.
PMID- 17029781
TI - Reagentless biosensor for hydrogen peroxide based on immobilization of protein in
zirconia nanoparticles enhanced grafted collagen matrix.
AB - A novel matrix, zirconia nanoparticles enhanced grafted collagen (ZrO2-grafted
collagen) hybrid composite, for immobilization of protein and biosensing was
developed. The scanning electron microscopy, UV-vis and Fourier transform
infrared spectra, and electrochemical measurements showed that the matrix was
well biocompatible and could retain the bioactivity of immobilized protein to a
large extent. The direct electron transfer of the immobilized myoglobin (Mb)
exhibited a couple of stable and well-defined redox peaks with the formal
potential of -336 mV (versus SCE) in 0.1M pH 7.0 PBS. This matrix could
accelerate the electron transfer between Mb and the electrode with a surface
controlled process and an electron transfer rate constant of 3.58+/-0.35s-1 at 10
500 mVs-1. The Mb immobilized in the matrix showed a high thermal stability up to
70 degrees C and an electrocatalytic activity to the reduction of hydrogen
peroxide (H2O2) without the help of an electron mediator. The linear response
range of the biosensor to H2O2 concentration was from 1.0 to 85.0 microM with the
limit of detection of 0.63 microM at a signal-to-noise ratio of 3sigma. The
biosensor exhibited high sensitivity, acceptable stability and reproducibility.
This work opened a way for the further study on the direct electron transfer and
biosensing application of the immobilized protein in collagen-related matrices.
PMID- 17029782
TI - Ischemic preconditioning-induced activation of ERK1/2 in the rat hippocampus.
AB - We investigated the activation and cellular localization of the extracellular
signal-regulated kinases ERK1/2 in a rat model of ischemic tolerance induction.
Adult male Sprague-Dawley rats were subjected to 3 min of sublethal ischemic
preconditioning. Activation of ERK1/2 showed the characteristic time- and cell
dependent patterns. Rapid and short-lasting activation of ERK after 3 min of
cerebral ischemia was noted immediately in the dentate granule cells and mossy
fibers of the hippocampus, and then occurred sequentially in CA3 and CA1 neurons
and dentate hilar neurons at 10 min. Phosphorylation of ERK1/2 in hippocampal
neurons returned to the basal level in an ordered manner. Basal level
phosphorylation was attained first, at 30 min, by the CA1 neurons, and was then
observed in CA3 and granule cells by 1 h and noted in some dentate hilar neurons
at 12 h. By contrast, phosphorylation of ERK1/2 in mossy fibers and the CA1
dendritic field was sustained for at least 3 d. Transient activation of ERK1/2
was induced also in astrocytes of the dentate hilar region at 1 d post
stimulation. These data demonstrate that the short cerebral-ischemic
preconditioning induced rapid and transient activation of ERK1/2 in tolerance
acquired CA1 neurons as well as in ischemia-resistant CA3 and dentate granule
cells, and that the short preconditioning sustained activation in mossy fibers
and neuropil areas, suggesting that ERK1/2 activation may be involved in the
mechanism of ischemic tolerance in the rat hippocampus.
PMID- 17029783
TI - COMT genotype, gender and cognition in community-dwelling, older adults.
AB - A common polymorphism (Val158Met) in the gene encoding for the catechol-O
methyltransferase (COMT) enzyme has been associated with differences in
prefrontal cognitive function in schizophrenic patients and healthy adults. While
several studies indicate that the Met allele is associated with better
performance on measures of executive function, working memory and verbal fluency,
results have been inconsistent. Furthermore, fewer studies have investigated this
relationship in older adults, a group known to experience impairments in
prefrontal cognitive functions. Additionally, findings vary according to the
gender distribution of study participants. We examined whether COMT genotype
interacted with gender to impact cognition in a cohort of 163 healthy, older
adults. Memory, verbal ability and areas of prefrontal cognitive function,
including attention, speed-of-processing, and executive function, were assessed.
We found no significant association between COMT genotype and any cognitive
measure. However, gender interacted with COMT genotype to impact cognitive
performance. Males homozygous for the Val allele performed better than both the
Val/Met and Met/Met groups on measures of delayed recall. Heterozygous women
performed better than their homozygous counterparts on the measure of verbal
ability. These findings suggest that gender may be an important variable in
consideration of the impact of COMT on cognition. Further, when gender is taken
into consideration, any negative impact of COMT genotype may extend to cognitive
domains other than those associated with prefrontal regions.
PMID- 17029784
TI - Transient cognitive deficits are associated with the reversible accumulation of
amyloid precursor protein after mild traumatic brain injury.
AB - Mild traumatic brain injury (MTBI) may frequently cause transient behavioral
abnormalities without observable morphological findings. In this study, we
investigated neuropathological mechanisms underlying transient cognitive deficits
after MTBI. Mongolian gerbils were subjected to experimental MTBI. At various
time points after injury, behavioral changes were evaluated by the open-field
test and T-maze test, and immunohistochemistry of microtubule-associated protein
(MAP2) and amyloid precursor protein (APP) was performed to examine disruptions
of the neuronal cytoskeleton and axonal transport, respectively. Transient
cognitive deficits were observed after MTBI. Sustained MAP2 loss was found within
the cortical impact site, but not the hippocampus. Transient APP accumulation at
the same time as transient cognitive deficits occurred in the ipsilateral
hemisphere, particularly in the subcortical white matter. These results suggest
that the axonal dysfunction indicated by the reversible APP accumulation in the
white matter, but not the sustained neuronal cytoskeletal damage reflected by the
cortical MAP2 loss confined to the impact site, is responsible for the transient
functional deficits after MTBI.
PMID- 17029785
TI - V180I mutation of the prion protein gene associated with atypical PrPSc
glycosylation.
AB - A valine to isoleucine mutation at residue 180 was identified in a French patient
with Creutzfeldt-Jakob disease (CJD). The mutation is located in the close
vicinity of one of the two N-glycosylation sites of the cellular prion protein
(PrP(C)). Western blot analysis revealed accumulation in the brain of the
pathogenic proteinase K-resistant PrP (PrP(Sc)) isoform with the notable absence
of the diglycosylated band. The mutant protein expressed in CHO cells was
correctly glycosylated, suggesting that the atypical glycosylation pattern of
PrP(Sc) was not due to the mutation at position 180. These results suggest that
the diglycosylated form of the mutant PrP(180I) prevents its conversion into the
pathogenic mutant form PrP(Sc180I), supporting a central role of N-linked glycan
chains in the PrP conversion process.
PMID- 17029786
TI - TuBaFrost 3: regulatory and ethical issues on the exchange of residual tissue for
research across Europe.
AB - The regulatory regimes for research with residual tissue and accompanying data
differ widely between countries in the European Union (EU): from specific consent
to opt-out or even no consent at all. This could greatly hamper research where
the exchange of tissue and accompanying data has become the gold standard, like
in TubaFrost. Instead of adhering to international guidelines, which have a
democratic deficit, or an attempt for a new set of possible harmonising rules,
TubaFrost chose to create a coordinating rule: if tissue may legitimately be used
for a certain kind of research in the country where it was taken and under whose
jurisdiction the patient falls, it may also be used for such research in the
country where it is sent to in the context of a scientific program even if in
that other country other regulations would apply for research with residual
tissue taken from patients under their jurisdiction. This coordinating rule has a
sound basis in EU law in general and will solve the problems related to diverging
national regulatory regimes in the case of cross national research with residual
tissue.
PMID- 17029787
TI - TuBaFrost 5: multifunctional central database application for a European tumor
bank.
AB - Developing a tissue bank database has become more than just logically arranging
data in tables combined with a search engine. Current demand for high quality
samples and data, and the ever-changing legal and ethical regulations mean that
the application must reflect TuBaFrost rules and protocols for the collection,
exchange and use of tissue. To ensure continuation and extension of the TuBaFrost
European tissue bank, the custodianship of the samples, and hence the decision
over whether to issue samples to requestors, remains with the local collecting
centre. The database application described in this article has been developed to
facilitate this open structure virtual tissue bank model serving a large group.
It encompasses many key tasks, without the requirement for personnel, hence
minimising operational costs. The Internet-accessible database application
enables search, selection and request submission for requestors, whereas
collectors can upload and edit their collection. Communication between requestor
and involved collectors is started with automatically generated e-mails.
PMID- 17029788
TI - Randomized controlled trial of exercise for chronic whiplash-associated
disorders.
AB - Whiplash-associated disorders are common and incur considerable expense in social
and economic terms. There are no known effective treatments for those people
whose pain and disability persist beyond 3 months. We conducted a randomized,
assessor-blinded, controlled trial at two centres in Australia. All participants
received 3 advice sessions. In addition the experimental group participated in 12
exercise sessions over 6 weeks. Primary outcomes were pain intensity, pain
bothersomeness and function measured at 6 weeks and 12 months. Exercise and
advice was more effective than advice alone at 6 weeks for all primary outcomes
but not at 12 months. The effect of exercise on the 0-10 pain intensity scale was
-1.1 (95%CI -1.8 to -0.3, p=0.005) at 6 weeks and -0.2 (0.6 to -1.0, p=0.59) at
12 months; on the bothersomeness scale the effect was -1.0 (-1.9 to -0.2,
p=0.003) at 6 weeks and 0.3 (-0.6 to 1.3, p=0.48) at 12 months. The effect on
function was 0.9 (0.3 to 1.6, p=0.006) at 6 weeks and 0.6 (-0.1 to 1.4, p=0.10)
at 12 months. High levels of baseline pain intensity were associated with greater
treatment effects at 6 weeks and high levels of baseline disability were
associated with greater treatment effects at 12 months. In the short-term
exercise and advice is slightly more effective than advice alone for people with
persisting pain and disability following whiplash. Exercise is more effective for
subjects with higher baseline pain and disability.
PMID- 17029789
TI - Less calcemic Vitamin D analogs enhance creatine kinase specific activity and
modulate responsiveness to gonadal steroids in the vasculature.
AB - Vitamin D receptors are widely expressed in the cardiovascular system, in which
Vitamin D and its metabolites exert a variety of biological activities such as
regulation of cellular proliferation and differentiation, cell calcium transients
and cell energy metabolism in vitro. The latter is mediated through the control
of the brain type creatine kinase specific activity (CK), which serves to provide
a readily available reservoir for ATP generation under increased work-load. In
the present study we undertook to assess the role of Vitamin D on energy
metabolism in the rat heart and aorta in vivo by using CK, which is a key energy
metabolizing enzyme and compare Vitamin D depleted and repleted animals. Vascular
tissues from female or male Vitamin D-depleted rats showed 61-80% lower CK
activity in the aorta (Ao) and left ventricle of the heart (Lv) than control,
Vitamin D-replete rats. Moreover, neither estradiol-17beta (E2) nor
dihydrotestosterone (DHT), which increases CK specific activity in Ao and Lv of
intact female or male rats, respectively, were able to stimulate CK in Vitamin D
depleted rats. Treatment of intact female rats for 2 weeks or 2 months with the
less-calcemic Vitamin D analogs JKF 1624F2-2 (JKF) or QW 1624F2-2 (QW) (Fig. 1),
did not significantly affect CK specific activity. However, after pretreatment
with these analogs, there was an up regulation of the E2-induced CK response in
Ao and Lv. In intact female rats, all Vitamin D analogs also potentiated the in
vivo CK response to the SERMs raloxifene (Ral) and tamoxifen (TAM) in Ao and Lv.
However the inhibitory effect of Ral or TAM on E2-induced CK activity was lost
after pretreatment with Vitamin D analogs. The non-calcemic analog CB 1093 (CB)
induced a significant increase in estradiol receptor alpha (ERalpha) protein in
both myocardial and aortic tissue from intact and from ovariectomized female
rats. Collectively, these results indicate that Vitamin D analogs modulate cell
energy homeostasis in vascular tissues through induction of CK and up regulation
of the response and sensitivity of CK in vascular tissues to E2 and to SERMs,
possibly through via an increase in ERalpha protein in female derived organs.
These results corroborate our previous in vitro studies in human vascular cells
and further suggest that the Vitamin D system plays an important physiological
role in maintaining normal cell energy reservoir in the vasculature.
PMID- 17029790
TI - Genotypic characterisation of Indian cattle, buffalo and sheep isolates of
Echinococcus granulosus.
AB - Twelve isolates of Echinococcus granulosus, collected from domestic animals,
including cattle, buffalo and sheep were analysed for DNA nucleotide sequence
variation within mitochondrial cytochrome c oxidase I (coxI), NADH dehydrogenase
subunit I (nadI) and internal transcribed spacer gene I (ITS1). After analysis of
sequence information this was found that the fragment size of ITS1 of buffalo
isolate was more in comparison to cattle and sheep isolates. Based on the nadI
genotype this was found that Indian cattle, buffalo and sheep isolates could be
grouped into E. granulosus sensu stricto. Based on coxI genotype two sheep
isolates and one buffalo isolate were homologous to G2 genotype. Rests of the
isolates were microvariants of G2 genotype. Presence of G2 genotype in buffalo is
the first report of this genotype from this host.
PMID- 17029791
TI - Autohydrolysis of agricultural residues: study of reaction byproducts.
AB - Samples of rice husks and corn cobs were subjected to hydrothermal treatments in
aqueous media under conditions leading to maximal xylooligomer concentration, and
the reaction liquors were extracted with dichloromethane (DCM) to assess the type
and amount of reaction byproducts with potential application as food ingredients
and cosmetics. The identified DCM-soluble compounds were classified in four
categories (sugar-derived compounds, lignin-derived compounds, nitrogen
containing compounds and fatty acids). The experimental results were compared
with literature data.
PMID- 17029792
TI - Preparation and characterization of activated carbon from rice bran.
AB - A study on the preparation of rice bran-based activated carbon was conducted,
with and without an acid treatment step prior the activation process. The
influence of the activation time on the structure of the activated carbons was
evaluated. The acid treatment had a significant positive influence on sorption
properties. The rice bran-activated carbon presented a BET surface area of
652m(2)g(-1) and a pore volume of 0.137cm(3)g(-1), with mesopores predominance
(ca. 55%). These experimental results indicated the potential use of rice bran as
a precursor in the activated carbon preparation process, thus representing an
economically promising material.
PMID- 17029793
TI - Purification and characterization of butyrate-induced protein phosphatase
involved in apoptosis of Ehrlich ascites tumor cells.
AB - Short chain fatty acids including butyrate exhibit wide variety of biological
effects towards cell growth, morphology and gene expression. In this report, we
study the mechanism by which butyrate (BuA) modulates the expression of protein
phosphatase when treated to the cells. As a model system, we used Ehrlich Ascites
Tumor (EAT) cells in which BuA-treatment induces expression of a protein
phosphatase enzyme. Subsequently, BuA-induced protein phosphatase has been
biochemically purified and characterized. Further, pretreatment of caspase-3
inhibitor abolished the activity of BuA-induced protein phosphatase indicating
the involvement of caspase-3 in the activation of BuA-induced protein
phosphatase. In addition, the relationship between BuA-induced protein
phosphatase and apoptosis has been verified. Activation of endonuclease-II has
been shown in BuA-treated EAT cells and that activity was completely inhibited by
sodium orthovanadate, a tyrosine phosphatase inhibitor suggesting that
endonuclease-II may serve as a possible down-stream target for BuA-induced
protein phosphatase. Together, the data suggest that activation of protein
phosphatase may be an early and essential step in BuA-mediated apoptotic
signaling pathway in EAT cells.
PMID- 17029794
TI - On the simulation of enzymatic digest patterns: the fragmentation of oligomeric
and polymeric galacturonides by endo-polygalacturonase II.
AB - A simulation methodology for predicting the time-course of enzymatic digestions
is described. The model is based solely on the enzyme's subsite architecture and
concomitant binding energies. This allows subsite binding energies to be used to
predict the evolution of the relative amounts of different products during the
digestion of arbitrary mixtures of oligomeric or polymeric substrates. The
methodology has been specifically demonstrated by studying the fragmentation of a
population of oligogalacturonides of varying degrees of polymerization, when
digested by endo-polygalacturonase II (endo-PG II) from Aspergillus niger.
PMID- 17029795
TI - Pyrroloquinoline quinone nutritional status alters lysine metabolism and
modulates mitochondrial DNA content in the mouse and rat.
AB - Pyrroloquinoline quinone (PQQ) added to purified diets devoid of PQQ improves
indices of perinatal development in rats and mice. Herein, PQQ nutritional status
and lysine metabolism are described, prompted by a report that PQQ functions as a
vitamin-like enzymatic cofactor important in lysine metabolism (Nature 422 [2003]
832). Alternatively, we propose that PQQ influences lysine metabolism, but by
mechanisms that more likely involve changes in mitochondrial content. PQQ
deprivation in both rats and mice resulted in a decrease in mitochondrial
content. In rats, alpha-aminoadipic acid (alphaAA), which is derived from alpha
aminoadipic semialdehyde (alphaAAS) and made from lysine in mitochondria, and the
plasma levels of amino acids known to be oxidized in mitochondria (e.g., Thr,
Ser, and Gly) were correlated with changes in the liver mitochondrial content of
PQQ-deprived rats, but not PQQ-supplemented rats. In contrast, the levels of NAD
dependent alpha-aminoadipate-delta-semialdehyde dehydrogenase (AASDH), a
cytosolic enzyme important to alphaAA production from alphaAAS, was not
influenced by PQQ dietary status. Moreover, the levels of U26 mRNA were not
significantly changed even when diets differed markedly in PQQ and dietary lysine
content. U26 mRNA levels were measured, because of U26's proposed, albeit
questionable role as a PQQ-dependent enzyme involved in alphaAA formation.
PMID- 17029796
TI - C-phycocyanin transcriptionally regulates uPA mRNA through cAMP mediated PKA
pathway in human fibroblast WI-38 cells.
AB - We have previously demonstrated the efficacy of c-phycocyanin in up-regulation of
urokinase-type plasminogen activator (uPA) in bovine endothelial cell line.
However, the mechanism of action and pathway elucidation in uPA regulation is
unclear. In experiments reported here, we have investigated the mechanism of
action of c-phycocyanin (c-pc) induced uPA gene modulation in human fibroblast
(WI-38) cell line. ELISA test confirmed that c-pc increased the uPA antigen
whereas PAI-1 antigen level was unaffected. Treatment of cells with c-pc
significantly (P<0.05) enhanced the uPA mRNA level in a dose (50 microg/ml) and
time dependent (up to 4 h) manner. This effect of c-pc was abolished by treatment
with dichloro-1-beta-D-ribofuranosyl benzamidazole (DRB) (10 microg/ml). Co
treatment of c-pc with 200 microg/ml cycloheximide (CHX), translation inhibitor,
resulted in over accumulation of uPA mRNA. These results suggest that uPA
induction by c-pc is transcriptionally regulated and does not require de novo
protein synthesis. We also provide evidence that c-pc stimulates uPA gene through
cAMP dependent pathway as adenylyl cyclase (AC) inhibitor, dideoxyadenosine (DDA)
significantly inhibited the uPA mRNA expression and co-treatment with adenylyl
cyclase analogue, dBcAMP recovered the effect of c-pc on gene activity.
Furthermore, the present investigation provides evidence on the regulatory
pathway involved in the c-pc stimulus. C-pc induced uPA expression was completely
inhibited by PKA inhibitor (KT 5200), indicating the regulation is dependent on
PKA pathway. Elimination of PKC pathway components by prolonged incubation with
excess amount of phorbol 12-myristate 13-acetate (PMA) failed to abolish the c-pc
effect on uPA expression indicating the regulation is independent of PKC pathway.
Taken together, our data indicate that uPA gene regulation by c-pc is
transcriptionally controlled through cAMP mediated PKA pathway.
PMID- 17029797
TI - Synthesis and anti-microbial activity of pyrazolylbisindoles--promising anti
fungal compounds.
AB - A series of pyrazolylbisindole derivatives have been synthesized by reacting
substituted pyrazole aldehydes with substituted indoles using phosphotungstic
acid, a Keggin type heteropoly acid as catalyst. The synthesized
pyrazolylbisindoles were evaluated for anti-microbial activities. The effect of
pyrazolylbisindoles on the mycelial growth of plant pathogenic fungi is revealed.
Entries 3c and 3d emerged as the most interesting compounds in this series
exhibiting excellent anti-fungal activity.
PMID- 17029798
TI - Prenatal development of hypothalamic neuropeptide systems in the nonhuman
primate.
AB - In the rodent, arcuate nucleus of the hypothalamus (ARH)-derived neuropeptide Y
(NPY) and proopiomelanocortin (POMC) neurons have efferent projections throughout
the hypothalamus that do not fully mature until the second and third postnatal
weeks. Since this process is likely completed by birth in primates we
characterized the ontogeny of NPY and melanocortin systems in the fetal Japanese
macaque during the late second (G100), early third (G130) and late third
trimesters (G170). NPY mRNA was expressed in the ARH, paraventricular nucleus
(PVH), and dorsomedial nucleus of the hypothalamus (DMH) as early as G100. ARH
derived NPY projections to the PVH were initiated at G100 but were limited and
variable; however, there was a modest increase in density and number by G130. ARH
NPY/agouti-related peptide (AgRP) fiber projections to efferent target sites were
completely developed by G170, but the density continued to increase in the
postnatal period. In contrast to NPY/AgRP projections, alphaMSH fibers were
minimal at G100 and G130 but were moderate at G170. This study also revealed
several significant species differences between rodent and the nonhuman primate
(NHP). There were few NPY/catecholamine projections to the PVH and ARH prior to
birth, while projections were increased in the adult. A substantial proportion of
the catecholamine fibers did not coexpress NPY. In addition, cocaine and
amphetamine-related transcript (CART) and alpha-melanocyte stimulating hormone
(alphaMSH) were not colocalized in fibers or cell bodies. As a consequence of the
prenatal development of these neuropeptide systems in the NHP, the maternal
environment may critically influence these circuits. Additionally, because
differences exist in the neuroanatomy of NPY and melanocortin circuitry the
regulation of these systems may be different in primates than in rodents.
PMID- 17029799
TI - 5-HT activates vagal afferent cell bodies in vivo: role of 5-HT2 and 5-HT3
receptors.
AB - Occipital artery (OA) injections of 5-HT elicit pronounced reductions in heart
rate and mean arterial blood pressure (MAP) in urethane-anesthetized rats by
activation of vagal afferent cell bodies in the ipsilateral nodose ganglion. In
contrast, internal carotid artery (ICA) and i.v. injections elicit similar
cardiovascular responses by activation of peripheral vagal afferent terminals.
The aim of this study was to examine the roles of 5-HT3 and 5-HT2 receptors in
the 5-HT-induced activation of vagal afferent cell bodies and peripheral afferent
terminals in urethane-anesthetized rats. OA, ICA and i.v. injections of 5-HT
elicited dose-dependent reductions in heart rate and MAP that were virtually
abolished after i.v. administration of the 5-HT3 receptor antagonists, MDL 7222
or ICS 205-930. The responses elicited by the OA injections of 5-HT were markedly
diminished after i.v. injection of the 5-HT2 receptor antagonists, xylamidine or
ketanserin, whereas the responses elicited by i.v. or ICA injections of 5-HT were
not affected. The present findings suggest that (1) 5-HT3 and 5-HT2 receptor
antagonists gain ready access to nodose ganglion cells upon i.v. administration,
and (2) functional 5-HT3 and 5-HT2 receptors exist on the cell bodies of vagal
afferent neurons mediating the cardiovascular responses elicited by OA injections
of 5-HT. These findings also support a wealth of evidence that 5-HT3 receptors
exist on the peripheral terminals of vagal afferents, and although they do not
discount the possibility that 5-HT2 receptors exist on peripheral vagal afferent
terminals, it appears that activation of these receptors does not have pronounced
effects on 5-HT3 receptor activity on terminals that mediate the hemodynamic
responses to 5-HT.
PMID- 17029800
TI - Dopamine innervation of the monkey mediodorsal thalamus: Location of projection
neurons and ultrastructural characteristics of axon terminals.
AB - Dopamine (DA) axons and receptors have recently been identified in the primate
thalamus, including the mediodorsal thalamic nucleus (MD). In order to determine
whether the DA innervation of the primate MD shares the anatomical features of
the mesocortical or nigrostriatal DA projections, we performed tract-tracing and
immunocytochemistry studies in macaque monkeys (Macaca fascicularis) to identify
the location of the DA neurons that project to MD and immuno-electron microscopy
to determine the distribution of the dopamine transporter (DAT) in axons within
the MD. Similar to the mesocortical projection, retrogradely-labeled, tyrosine
hydroxylase-containing neurons were present in dorsal tier ventral mesencephalic
nuclei, such as the ventral tegmental area and the dorsal portion of the
substantia nigra pars compacta. In contrast, no dual-labeled neurons were present
in the ventral tier nuclei, the primary origin of the nigrostriatal DA pathway.
In addition, like the DA projection to the prefrontal cortex, DAT
immunoreactivity was predominantly localized to the pre-terminal portion of axons
in the MD, and was infrequently found in association with synaptic vesicles, in
contrast to nigrostriatal DA axons. These findings indicate that the DA
projection to the MD shares anatomical features with the mesocortical DA system,
suggesting that the functional properties of DA neurotransmission in the MD might
be more similar to those in the cortex than in the striatum.
PMID- 17029801
TI - Occipital artery injections of 5-HT may directly activate the cell bodies of
vagal and glossopharyngeal afferent cell bodies in the rat.
AB - The primary objective of this study was to determine whether circulating factors
gain direct access to and affect the activity of vagal afferent cell bodies in
the nodose ganglia and glossopharyngeal afferents cell bodies in the petrosal
ganglia, of the rat. We found that the occipital and internal carotid arteries
provided the sole blood supply to the nodose ganglia, and that i.v. injections of
the tracer, Basic Blue 9, elicited strong cytoplasmic staining in vagal and
glossopharyngeal afferent cell bodies that was prevented by prior ligation of the
occipital but not the internal carotid arteries. We also found that occipital
artery injections of 5-HT elicited pronounced dose-dependent reductions in heart
rate and diastolic arterial blood pressure that were (1) virtually abolished
after application of the local anesthetic, procaine, to the ipsilateral nodose
and petrosal ganglia, (2) markedly attenuated after transection of the
ipsilateral vagus between the nodose ganglion and brain and virtually abolished
after subsequent transection of the ipsilateral glossopharyngeal nerve between
the petrosal ganglion and the brain, (3) augmented after ipsilateral transection
of the aortic depressor and carotid sinus nerves, and (4) augmented after
transection of all ipsilateral glossopharyngeal and vagal afferent nerves except
for vagal cardiopulmonary afferents. These findings suggest that blood-borne 5-HT
in the occipital artery gains direct access to and activates the cell bodies of
vagal cardiopulmonary afferents of the rat and glossopharyngeal afferents of
undetermined modalities.
PMID- 17029802
TI - Dysphagic phagocytosis by thyroid epithelium.
PMID- 17029803
TI - The risk factor association syndrome as a barisystemic syndrome: a view on
obesity and the metabolic syndrome.
AB - A number of factors are known to be associated to an increased risk of
cardiovascular disease. High blood pressure, lipid abnormalities, type 2 diabetes
mellitus, obesity and sleep apnea may act as isolated risk factors but,
frequently, coexist in the same person. Studies involving surgery aimed at weight
reduction (bariatric surgery - from barys, the greek term for heavy) have
consistently shown a high probability of resolution of major risk factors, namely
of diabetes, hyperlipidemia and hypertension, associated to weight reduction.
Data in a similar direction were obtained after weight reduction was reached by
means of pharmacological therapy. Excessive weight thus may stand as the probable
cause for a number of cardiovascular risk factors, at least in many patients with
an adequate genetic background. The moment may have come to focus on causality
and to suggest that the risk factor association syndrome, in patients with
overweight/obesity, may be defined as the systemic consequences of excessive
weight, including hormonal, body habitus, metabolic, hemodynamic and respiratory
parameters. A suitable name for the syndrome might be the barisystemic syndrome.
PMID- 17029804
TI - Electroatriography - time-frequency analysis of atrial fibrillation from modified
12-lead ECG configurations for improved diagnosis and therapy.
AB - Current atrial fibrillation (AF) management guidelines suggest that initially a
decision must be made to apply either a rate control or rhythm control strategy
in the individual patient. However, patients' selection remains substantially
empirical and the strategy initially chosen often proves unsuccessful and
alternative therapies must be adopted. Thus, it seems desirable to develop and
apply tests that quantify AF disease state and guide AF management. The overall
hypothesis of this paper is that time-frequency analysis of AF from modified 12
lead ECG configurations will improve AF management beyond current diagnostic and
therapeutic standards. In particular, we present a novel concept in which 12-lead
ECG configurations are modified for time-frequency analysis of AF
(electroatriography). While five electrodes (VR, VL, VF, V1, V2) are placed in
the conventional position, the other four electrodes (V3, V4, V5, V6) are
empirically repositioned anterior or posterior over the atria. By applying
spatiotemporal QRST cancellation and time-frequency analysis to these recordings
in 19 patients with persistent AF, fibrillatory rate dispersion among individual
anterior (25+/-14 fibrillations per minute, fpm) and posterior leads (16+/-11fpm)
as well as individual anterior/posterior rate gradients ranging between -24 and
+116fpm could be identified. Consequently, the portrayed techniques may form the
conceptual basis for individualized noninvasive characterization of AF.
Initiation of further studies using the described techniques in different AF
subsets, for comparisons with intracardiac recordings and outcome of different
therapies, e.g. cardioversion, antiarrhythmic drug and ablation therapy may be
stimulated.
PMID- 17029805
TI - Chemisorption of proteins and their thiol derivatives onto gold surfaces:
characterization based on electrochemical nonlinearity.
AB - This study was conducted to monitor the electrochemical responses of two proteins
(bovine serum albumin (BSA) and gelatin) and their thiol derivatives adsorbed
onto gold (Au) electrodes, which were analyzed by a "nonlinear" impedance method.
A sinusoidal voltage is applied to a protein-containing aqueous solution and the
waveform of the output current is analyzed by fast Fourier transformation (FFT).
The intensities of the higher harmonics in the FFT varied with the species of
protein and their thiol derivatives, and with time. From the higher harmonics,
voltage-dependent capacitance and conductance were quantitatively evaluated to
differentiate the state of adsorbed protein. Adsorption and desorption
characteristics of BSA and its thiol derivative on the Au surface were
continuously measured by a quartz crystal microbalance (QCM) in situ. The
microscopic state of thiol-derivatized BSA adsorbed onto the Au surface was
imaged by atomic force microscopy (AFM). In general, thiol-derivatized proteins
were tightly adsorbed on the Au surface and showed no desorption. The present
electrochemical measurements clearly differentiated adsorption characteristics of
physically adsorbed (physisorbed) and chemically adsorbed (chemisorbed) proteins
on Au surfaces.
PMID- 17029806
TI - Theoretical basis for differential scanning calorimetric analysis of multimeric
proteins.
AB - A new general equation simulating irreversible DSC transitions of multimeric
proteins was developed. The equation put forward here is the result of an
improved mathematical re-elaboration of the classical Lumry-Eyring models, where
no restrictive a priori assumptions are made on the kinetic constraints of the
denaturation process, or on the enthalpy of the final denatured state. In order
to test the wide applicability of this new effective theoretical tool, a series
of DSC transitions were simulated with the aim of determining the effects of all
relevant thermodynamic, kinetic or experimental parameters on the shape of DSC
profiles. Moreover, the classical equations used widely in DSC investigations for
the calculus in both kinetic parameters and changes of molecularity, were studied
in the light of the model developed here, highlighting, in each case, their
rather limited applicability. The new approach proposed in this article was
applied to study the thermal denaturation of an hexameric protein (Glucosamine-6
phosphate deaminase), putting in evidence the practical applicability of the
theoretical equations developed.
PMID- 17029807
TI - Thermodynamics of sequence-specific protein-DNA interactions.
AB - The molecular recognition processes in sequence-specific protein-DNA interactions
are complex. The only feature common to all sequence-specific protein-DNA
structures is a large interaction interface, which displays a high degree of
complementarity in terms of shape, polarity and electrostatics. Many molecular
mechanisms act in concert to form the specific interface. These include
conformational changes in DNA and protein, dehydration of surfaces,
reorganization of ion atmospheres, and changes in dynamics. Here we review the
current understanding of how different mechanisms contribute to the
thermodynamics of the binding equilibrium and the stabilizing effect of the
different types of noncovalent interactions found in protein-DNA complexes. The
relation to the thermodynamics of small molecule-DNA binding and protein folding
is also briefly discussed.
PMID- 17029808
TI - Comparison between breast volume measurement using 3D surface imaging and
classical techniques.
AB - Quantification of the complex breast region can be helpful in breast surgery,
which is shaped by subjective influences. However, there is no generally
recognized method for breast volume calculation. Three-dimensional (3D) body
surface imaging represents a new alternative for breast volume computation. The
aim of this work was to compare breast volume calculation with 3D scanning and
three classic methods, focusing on relative advantages, disadvantages, and
reproducibility. Repeated breast volume calculations of both breasts in six
patients (n=12) were performed using a 3D laser scanner, nuclear magnetic
resonance imaging (MRI), thermoplastic castings, and anthropomorphic
measurements. Mean volumes (cc) and mean measurement deviations were calculated,
and regression analyses were performed. MRI showed the highest measurement
precision, with a mean deviation (expressed as a percentage of mean breast
volume) of 1.56+/-0.52% compared with 2.27+/-0.99% for the 3D scanner, 7.97+/
3.53% for thermoplastic castings, and 6.26+/-1.56% for the anthropomorphic
measurements. Breast volume calculations using MRI showed the best agreement with
3D scanning measurement (r=0.990), followed by anthropomorphic measurement
(r=0.947), and thermoplastic castings (r=0.727). Compared with three classical
methods of breast volume calculation, 3D scanning provides acceptable accuracy
for breast volume measurements, better spatial interpretation of the anatomical
area to be operated on (due to lack of chest deformation), non-invasiveness, and
good patient tolerance. After this preliminary study and further development, we
believe that 3D body surface scanning could provide better preoperative planning
and postoperative control in everyday clinical practice.
PMID- 17029809
TI - Expression of the GLUT1 glucose transporter, p63 and p53 in thyroid carcinomas.
AB - Only few studies have evaluated the usefulness of the GLUT1 and p63 status of
thyroid carcinomas in revealing tumorigenesis. We studied GLUT1, p53, and p63
immunoexpression in a total of 86 cases of various thyroid carcinoma types to
determine the biological significance of GLUT1 and p63 expression in thyroid
carcinomas. GLUT1 was detected in six cases of anaplastic carcinoma and in one
case of poorly differentiated carcinoma with membranous staining. p63 was
detected in five cases of anaplastic carcinoma, in one case of poorly
differentiated carcinoma, and in five cases of papillary carcinoma with nuclear
positivity. p53 was detected in six cases of anaplastic carcinoma, in one case of
poorly differentiated carcinoma, and in one case of follicular carcinoma with
nuclear positivity. Five of seven cases of anaplastic carcinoma expressed all
three of these markers. The results suggest that GLUT1, p63, and p53 are not
expressed in well-differentiated thyroid carcinomas, and that they are usually
expressed late in the course of thyroid tumor progression. These data strongly
suggest that in anaplastic carcinomas, impairment of p53-mediated repression
results in increased GLUT1 and p63 expression, and that this probably reflects
the differential regulation of hypoxia-responsive pathways and basal/stem cell
regulatory pathways.
PMID- 17029810
TI - Standard free energies of binding of solute to proteins in aqueous medium. Part
1: Thermodynamic analysis for multicomponent system.
AB - Using an equilibrium dialysis technique, moles (Gamma(2)(1)) of cationic and
anionic surfactants bound per kilogram of proteins of various types in aqueous
media have been measured previously in this laboratory under different
physicochemical conditions. From a thermodynamic analysis in the present paper,
Gamma(2)(1) has been shown to be equal to the Gibbs relative excess of surfactant
per kilogram of protein at a measured value of solute activity, a(2). The values
of relative solvent excesses, Gamma(2)(1) (which are negative for surfactants)
can be estimated from values of Gamma(2)(1) and a(2). Using the Gibbs-Duhem
relationship for protein solution inside the dialysis bag and dialysate solutions
respectively at equilibrium, an integrated expression for the standard free
energy change, DeltaG(o) (in kilojoules per kilogram of protein for binding with
ligand as a result of the change of a(2) from zero to unity) can be calculated
from experimental data. The isopiestic vapour pressure technique was used
extensively for evaluation of negative binding (-Gamma(2)(1)) of inorganic salts
to proteins of different types for various values of a(2) of salts present in the
bulk media. With some modifications of our derived equations for free energy of
binding in such a system, DeltaG(o) has been evaluated for the change of mean
activity of electrolyte from zero to unity in the rational scale. DeltaG(o) is
positive since Gamma(2)(1) is negative and Gamma(2)(1) is positive for such ionic
systems. DeltaG(o) in all cases, however, are expressed in terms of the standard
state of reference of unit activity so that their magnitudes and sign can be
related to the relative affinities of a solute for binding with proteins in
aqueous media.
PMID- 17029811
TI - Fourier analysis of potential oscillations of a liquid membrane for the
discrimination of taste substances.
AB - Electrical potential oscillations were obtained across a liquid membrane composed
of nitrobenzene/picric acid placed between two aqueous phases in the presence of
various taste (i.e. salty, sweet and bitter) substances. The influence of these
compounds on electrical oscillations was studied using Fourier analysis to
establish a "fingerprint" of the substance that can be correlated with its taste
index. Various concentrations of each substance were tested to obtain a Fourier
spectrum with discrete peaks which can be further processed. The electrical
oscillations consisted of a number of weak damped oscillators, and the Fourier
spectra of these signals were found to have a number of discrete peaks of
decreasing amplitude at low frequencies (0-0.5 Hz). A correlation of the
frequency of the first peak of the Fourier spectrum with the taste index was
found for bitter substances, whereas for salty substances the amplitude of the
first two peaks of the spectrum was correlated with the taste index.
PMID- 17029812
TI - Store-operated Ca2+ entry: A STIMulating stOrai.
AB - Store-operated Ca2+ entry (SOCE) mediates much of the Ca2+ entry evoked by
receptors that stimulate phospholipase C. However, for 20 years, the plasma
membrane Ca2+ channel and the signal linking its activation to loss of Ca2+ from
the endoplasmic reticulum (ER) have eluded detection. But the search might now be
over. Two proteins, STIM1 (the ER Ca2+ sensor) and Orai1 (the Ca2+ channel), have
recently been identified as the missing links in SOCE.
PMID- 17029813
TI - Argonaute: A scaffold for the function of short regulatory RNAs.
AB - Argonaute is the central protein component of RNA-silencing mechanisms. It
provides the platform for target-mRNA recognition by short regulatory guide RNA
strands and the Slicer catalytic activity for mRNA cleavage in RNA interference.
Multiple Argonaute sub-families can be identified phylogenetically yet, despite
this diversity, molecular and sequence analyses show that Argonaute proteins
share common molecular properties and the capacity to function through a common
mechanism. Recently, the members of the Piwi sub-family have been shown to
interact with new classes of short regulatory RNAs, Piwi-interacting RNAs
(piRNAs) and repeat-associated small interfering RNAs (rasiRNAs), which has
implications for developmental processes and introduces a new dimension to the
field of RNA silencing.
PMID- 17029814
TI - [Epidemiology of candidemia: results of a one month French hospitals-based
surveillance study in 2004].
AB - INTRODUCTION: The aim of our study was to determinate the frequency of
candidemia, the species encountered and their susceptibility to antifungal agents
in French hospitals in 2004. METHODS: A prospective survey of septicaemia,
including candidaemia was conducted among 193 non teaching French hospitals
during October 2004. All bloodstream infections were reported and the bloodstream
isolates sent to two coordinating centers. Species identification and
susceptibility were performed by biologists as usual, and further confirmed by
use of alternative methods, including Minimal Inhibitory Concentration (MIC)
determination. RESULTS: The survey was effective in 93 hospitals, where 2013
bloodstream infections were noticed, including 46 candidaemia (2.3%). Candida sp.
Is the 7th pathogen responsible for bloodstream infection, without concern of the
origin of the infection. Candidaemia was hospital acquired in 80.4% of cases
(N=37/46). Candidaemia represents 0.7% (N=9/1211) of community-acquired
bloodstream infections but 4.5% (N=37/802) of nosocomial cases, placing Candida
sp. at the 5th row of frequency in this last group. No mistakes were noticed
during identification, but two strains were not named. After confirmation of
identification, species are distributed as follows: 23 C.albicans (50%), 13
C.glabrata (28.3%), 5 C.tropicalis (10.9%), 3 C.parapsilosis (6.5%), 1 C.krusei
(2.2%), and 1 C.kefyr (2.2%). The overall susceptibility is 97.7% for
amphotericin B, 93.2% for 5-fluorocytosin, 88.6% for fluconazole, 70.5% for
itraconazole, 95.5% for voriconzole and 100% of strains had very low MIC for
caspofungin. Concerning the two main species isolated, 95.5% of C.albicans
strains remain susceptible to fluconazole, but only 69% of C.glabrata strains.
Two strains, 1 C.albicans and 1 C.glabrata exhibit cross resistance to azoles.
The majority of amphotericin, fluconazole, and itraconazole decreased
susceptibility strains are found into C.glabrata strains, but susceptibility to 5
fluorocytosin and very low MCI to caspofungin remained in this species.
CONCLUSION: Our survey allowed us to get data from French non-teaching hospitals
in 2004 about frequency of candidaemia among septicaemia. Candida species
distribution and in vitro susceptibility patterns of the strains isolated.
Candidaemia is not a rare event, specially when septicaemia is nosocomially
acquired. C.albicans is the main species isolated and remains highly in vitro
susceptible to antifungals. One important feature is the frequency of C.glabrata
in our survey. Considering its decreased susceptibility to azoles, this finding
confirms the need for rapid identification of yeast isolated from bloodstream
samples, and antifungal susceptibility testing each time it is available.
PMID- 17029816
TI - The role of preoperative templating in total knee arthroplasty: comparison of
three prostheses.
AB - Templating of preoperative radiographs is routinely recommended prior to knee
arthroplasty. We performed this study to assess the reproducibility and accuracy
of the templates for three commonly used knee implants (PFC, Kinemax, Scorpio).
Six lower limb surgeons templated 10 patients for each of the three designs. The
inter- and intra-observer reliability and accuracy was calculated. There was
marked variation in the reliability of the templating with the tibial insert
scoring better than the femoral and the Kinemax being the most reproducible of
the three. In general, the intra-observer scores (kappa=0.57-0.81) were better
than the inter-observer ones (kappa=0.21-0.60). The Scorpio was the most
accurately templated of the three implants, with the percentage correlating with
what was actually implanted ranging from 55% to 62% for the femur and 72% to 75%
for the tibia, with no templated sizes more than one size different from the
actual implant. The other implants ranged from 38% to 42% for the femur and 53%
to 58% for the tibia with both having up to 3% more than 1 size difference from
the actual implant. We believe that the use of templating in total knee
arthroplasty should be interpreted with caution and we urge the development of
more accurate prosthesis sizing techniques.
PMID- 17029815
TI - [Evolution of the antibiotic resistance of Streptococcus pneumoniae from 1997 to
2004 at Hotel-Dieu de France, a university hospital in Lebanon].
AB - Various rates of Streptococcus pneumoniae with diminished susceptibility to
Penicillin G (PNSP) are reported worldwide, while resistance to cefotaxime and
ceftriaxone is actually increasing among S. pneumoniae. The aim of this survey
was to determine the evolution of the susceptibility and resistance of S.
pneumoniae at our hospital, throughout the years 1997-2004. 582 S. pneumoniae
strains, isolated from different patients with pulmonary disease, otitis media,
bacteremia and/or meningitis have been observed. MIC to benzylpenicillin (P),
ampicillin (AMP) and ceftriaxone (CRO) were determined by E-TEST. Susceptibility
to erythromycin (ERY), cotrimoxazole (SXT), tetracycline (TE) and rifampicin (RA)
were determined by agar diffusion. All tests were interpreted according to CA-SFM
guidelines. The percentage of PNSP varied between 49.6 and 69%. S. pneumoniae
with reduced susceptibility to benzylpenicillin had stable rates, while fully
resistant S. pneumoniae decreased significantly. Resistance to ampicillin varied
alongside with penicillin with a decrease of fully resistant S. pneumoniae.
Strains intermediate to ceftriaxone also decreased significantly while those
fully resistant were not detected, except for 1999 (1 strain). The resistance
(I+R) to SXT and TE remained stable with small variations, but resistance to ERY
increased up to 43% of isolated strains in 2004. Resistance to LVX and RA was
absent, with unexpected levels for RA (1 and 5%) in 2002 and 2003.
PMID- 17029817
TI - Judgments of causal efficacy under constant and changing interevent
contingencies.
AB - How do people judge constant and varying interevent contingencies? In two
experiments, 150 college students rated the efficacy of a potential cause (an
experimental fertilizer) of an effect (a plant's blooming). The prevailing
probabilistic interevent relation could remain constant for the entirety of the
problem or it could change without warning at the midway point: by contingency
reversal, by shifting from noncontingency to contingency, or by shifting from
contingency to noncontingency. Participants' trial-by-trial ratings sensitively
tracked the prevailing positive, negative, and noncontingent interevent
relations, even those that entailed an unsignaled change in contingency. Changes
in specific cells of the 2 x 2 contingency table differentially affected
participants' response to the altered interevent relations. All of this evidence
was well described by an associative account of contingency and causal judgments.
PMID- 17029818
TI - Derivation of V function for LR 115 SSNTD from its sensitivity to 220Rn in a
diffusion chamber.
AB - The sensitivity of the LR 115 detector inside a diffusion chamber to (220)Rn gas
concentration is dependent on the removed active layer thickness during chemical
etching. This dependence is related to the V function for the LR 115 detector
(where V is the ratio between the track etch velocity V(t) and the bulk etch
velocity V(b)) and the geometry of the diffusion chamber. The present paper
presents the experimentally determined relationship between the sensitivity of
the LR 115 detector inside a Karlsruhe diffusion chamber (determined from the
number of etched tracks completely penetrating the active cellulose nitrate
layer) and the removed active layer thickness. These data were used to derive the
V function for the LR 115 detector, which took the functional form of the Durrani
Green's function, i.e., V=1+((a1e-)(a2R+a3e(-a)4R))(1(-e)(-a5R)), with the best
fitted constants as a(1)=14.50, a(2)=0.50, a(3)=3.9 and a(4)=0.066.
PMID- 17029819
TI - Measurements of the half-life of 246Cm and the alpha-decay emission probabilities
of 246Cm and 250Cf.
AB - The alpha-decay half-life of Cm246 has been measured to be T(1/2)=4706 (40)yr by
means of the alpha-counting of ingrowth activity following the decay of a mass
separated source of the Cf250 parent nuclide. The alpha-decay emission
probabilities of Cm246 and Cf250 have also been determined with high precision
and have been compared with results from previous measurements. A new alpha-decay
branch of Cm246 to the 4(+) level of the ground-state band of the Pu242 daughter
nucleus has been identified and characterized.
PMID- 17029820
TI - RETRACTED: Synthesis of [(18)F]-labeled N(3)-substituted thymidine analogs: N(3)
[(18)F]fluoroethyl thymidine (N(3)-[(18)F]-FET) and N(3)-[(18)F]fluoropropyl
thymidine (N(3)-[(18)F]-FPRT) for PET.
AB - This article has been retracted consistent with Elsevier Policy on Article
Withdrawal. Please see http://www.elsevier.com/locate/withdrawalpolicy The
Publisher apologizes for any inconvenience this may cause.
PMID- 17029821
TI - Nonlinear oscillatory reaction of catalase induced by gradual entry of substrate.
AB - Characteristic oscillatory reactions were observed when hydrogen peroxide
migrated through semipermeable membrane into a solution of catalase. Measurements
were made with DO and an mV meter. Oscillation clearly occurred in the range
between 25 degrees C and 37 degrees C and between pH 6.0 and pH 7.6. It was also
shown that a driving force for the permeation of H2O2, which was the cause of the
oscillations, was a deviation from its equilibrium concentration. We made
simulations for oscillatory reactions on the basis of these findings. The result
indicated that considering the evaporation of O2 was necessary in order to
interpret the oscillatory reactions of catalase in addition to the slow entry of
substrate caused by deviation from the equilibrium concentration. The fact that
oscillations arise by using this method may provide an important insight into the
study of enzyme reactions mediated by membranes in living systems, because many
enzyme reactions take place with the mediation of a biomembrane.
PMID- 17029822
TI - Protein folding and wring resonances.
AB - The polypeptide chain of a protein is shown to obey topological constraints which
enable long range excitations in the form of wring modes of the protein backbone.
Wring modes of proteins of specific lengths can therefore resonate with molecular
modes present in the cell. It is suggested that protein folding takes place when
the amplitude of a wring excitation becomes so large that it is energetically
favorable to bend the protein backbone. The condition under which such structural
transformations can occur is found, and it is shown that both cold and hot
denaturation (the unfolding of proteins) are natural consequences of the
suggested wring mode model. Native (folded) proteins are found to possess an
intrinsic standing wring mode.
PMID- 17029823
TI - Chaos in a minimal model of the alternative pathway of the complement system.
AB - In previous work, we introduced a minimal model of the alternative pathway of the
complement. We also limited our analysis to a reduced set of parameter values
because, for some parameters, experimentally supported estimates were not found.
On the other hand, changes in value of some parameters may be a result of a
pathological condition. Therefore, here we extend our analysis and include a
wider range of values of five of the physiologically relevant parameters. For all
the parameters considered, we observe chaotic oscillations, and we construct
bifurcation diagrams using Poincare sections of local maxima.
PMID- 17029824
TI - An EPR investigation on the structural heterogeneity in copper azurin and
plastocyanin.
AB - The effects of cooling rate and of solvent properties on the active site
heterogeneity of two copper proteins, azurin and plastocyanin, have been
investigated at low temperature by electron paramagnetic resonance spectroscopy.
The spectra of theses proteins have been analyzed, by an accurate computer
simulation, in terms of a distribution of some relevant spin-Hamiltonian
parameters. The results show that the structural heterogeneity of both proteins,
quantified by the width of the distribution in the g and A tensors, is affected
by both the freezing procedure and the solvent composition. In particular, the g
distribution width is found to be reduced in the slow cooling regime; such a
reduction appearing more significant when glycerol is added to the protein
solutions. Despite of the similarity in the copper ion microenvironments of the
two proteins, the effects are more pronounced in azurin. The results are
discussed also in connection with the role played by the solvent and the rate of
freezing in featuring the conformational substate landscape.
PMID- 17029825
TI - Male-female differences in the risk of progression from first use to dependence
upon cannabis, cocaine, and alcohol.
AB - INTRODUCTION: We extend prior reports about the risk of dependence on specific
drugs by providing developmental-specific risk estimates for progression from
first use to meeting criteria for DSM-III-R dependence upon cannabis, cocaine, or
alcohol, as well as male-female differences. METHODS: The data are from the
National Comorbidity Survey, with a national probability sample of persons 15-44
years old in the United States, which included many respondents who used
cannabis, cocaine and alcohol on at least one occasion (n=3558, 1337, and 6149,
for cannabis, cocaine, and alcohol, respectively). Survival analysis procedures
provided cumulative risk estimates of progression from first use to dependence
upon each drug. RESULTS: The estimated risk of cannabis dependence among male
cannabis users was 1% in the first year after first use, and reached a peak at 4%
per year 2 years later, before declining. In contrast, the estimated risk of
cannabis dependence among female cannabis users remained at 1% per year for 3
years, without the peak. For both male and female cocaine users, the estimated
risk for developing cocaine dependence was 5 to 6% within the first year after
first use. Thereafter, the estimated risk declined from the peak value, with a
somewhat faster decline for females in the next 3 years after first use. For
alcohol, the estimated risk period extended for many years after the first drink,
with female drinkers becoming alcohol dependent at a rate of about 1% per year;
with somewhat higher risk for male drinkers. For both male and female drinkers,
the period of risk for developing alcohol dependence extended for a span of more
than 20 years since first use; for cannabis and cocaine, the estimated period of
risk was much shorter. COMMENT: There are male-female differences in the risk of
becoming cannabis dependent during the first several years after initiation of
cannabis use, less pronounced male-female differences for alcohol, and relatively
smaller male-female differences for cocaine. These results should interest
scientists whose focus is upon the origins of male-female differences in the
occurrence of drug dependence.
PMID- 17029826
TI - Increased glycophorin A somatic cell variant frequency in arsenic-exposed
patients of Guizhou, China.
AB - Exposure to arsenic through domestic burning arsenic-containing coal causes
various tumors in a population of Guizhou, China. The glycophorin A (GPA) assay
is a human mutation assay detecting somatic variation in erythrocytes expressing
the MN blood type, and was used to assess genotoxicity of arsenic-exposed
patients. Peripheral blood was collected from 18 adult healthy subjects and 40
arsenic-exposed patients in heparin-treated tubes. Erythrocytes were isolated,
fixed in formalin and immuno-labeled with fluorescent antibodies against GPA,
followed by flow cytometry analysis. Arsenic exposure increased the variant
frequency (expressed as the number of variant red cells per 10(6) erythrocytes):
NN, 3.7 in healthy subjects versus 21.2 in arsenic-exposed patients; N phi, 12.6
versus 33.1; MM, 13.1 versus 110; and M phi, 5.2 versus 20.3. The total GPA
variant frequency was increased about five-fold (34.7 in healthy subjects versus
185 in arsenosis patients). Furthermore, the variant frequency was significantly
higher in skin tumor-bearing patients: NN, 19.4 in arsenic-exposed non-tumor
patients versus 31.5 in tumor-bearing patients; N phi, 29.5 versus 54.5; MM, 102
versus 159; M phi, 15.9 versus 45.1. Total GPA variant frequency in arsenic
exposed patients bearing skin tumors was significantly increased compared to
patients without skin tumors (167 versus 290). The relationship between arsenic
exposure history and GPA variant frequency was less evident. These data
demonstrate that arsenic exposure is associated with mutations at the GPA locus,
an effect exaggerated in patients bearing arsenic-induced skin tumors. The
variant frequency of GPA could be a useful biomarker for arsenic exposure and
arsenic carcinogenesis.
PMID- 17029827
TI - Benzo[a]pyrene-induced DNA damage and p53 modulation in human hepatoma HepG2
cells for the identification of potential biomarkers for PAH monitoring and risk
assessment.
AB - To identify potential biomarkers for the monitoring and risk assessment of
benzo[a]pyrene (BaP), the oxidative stress-related DNA damage and p53
modification were investigated in human hepatoma HepG2 cells. Benzo[a]pyrene
exposure induced a decrease in the cell viability, but increased the antioxidant
enzyme activity as well as the DNA and lipid damage. The p53 protein activation
appeared to have been a downstream response to the benzo[a]pyrene-induced DNA
damage, suggesting p53 plays important roles in the defense against
benzo[a]pyrene-induced genotoxicity. The response of phosphorylated p53 may be
more sensitive towards benzo[a]pyrene exposure than normal p53. Following DNA
damage, the activation of p53 acts as a transcriptional regulator of several
target genes, including, p21 protein; a gene that encodes the Cdk inhibitor and
is induced by exposure to benzo[a]pyrene. The p53 mRNA level was increased after
the treatment of cells with benzo[a]pyrene, as well as following the induction of
p53 protein, suggesting the benzo[a]pyrene-stimulated p53 accumulation may also
be transcriptionally induced. The overall results suggest that benzo[a]pyrene
leads to serious DNA damage, which leads to the transcription of the p53 gene;
that the subsequent p53 protein accumulation up-regulates the cellular p21
protein. Oxidative DNA damage and p53 accumulation seem to be related to
benzo[a]pyrene toxicity; however, their potential as biomarkers in environmental
monitoring and risk assessment needs to be validated in the context of their
specificity and sensitivity.
PMID- 17029828
TI - Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of
Alzheimer disease.
AB - Transgenic mice carrying disease-linked forms of genes associated with Alzheimer
disease often demonstrate deposition of the beta-amyloid as senile plaques and
cerebral amyloid angiopathy. We have characterized the natural history of beta
amyloid deposition in APPswe/PS1dE9 mice, a particularly aggressive transgenic
mouse model generated with mutant transgenes for APP (APPswe: KM594/5NL) and PS1
(dE9: deletion of exon 9). Ex vivo histochemistry showed Abeta deposition by 4
months with a progressive increase in plaque number up to 12 months and a similar
increase of Abeta levels. In vivo multiphoton microscopy at weekly intervals
showed increasing beta-amyloid deposition as CAA and plaques. Although first
appearing at an early age, CAA progressed at a significantly slower rate than in
the Tg2576 mice. The consistent and early onset of beta-amyloid accumulation in
the APPswe/PS1dE9 model confirms its utility for studies of biochemical and
pathological mechanisms underlying beta-amyloid deposition, as well as exploring
new therapeutic treatments.
PMID- 17029830
TI - The Gibbs conference on biothermodynamics: origins and evolution.
AB - The Gibbs conference on biothermodynamics arose in the late 1980's as a 'self
organized' endeavor by researchers at eleven institutions of the US. Over a
period of 10 years these annual conferences have grown steadily in size. They
have fostered the development of new thermodynamic approaches and their
applications in biochemistry. By emphasizing participation by students and
postdoctoral fellows they have contributed significantly to the career
development of young scientists in this field.
PMID- 17029831
TI - Heat capacities of protein functional groups.
AB - Using a precise technique of scanning calorimetry the heat capacities of a series
of carboxylic acids and their sodium salts, alcohols, and N-substituted amides
have been measured from 5 to 100 degrees C. From these data, the partial molar
heat capacities of CH2, CONH, COOH, and COONa groups have been determined. It is
shown that the heat capacity of the CH(2) group in aqueous solution is
independent of the type of compound used for its determination, is positive at
low temperature, and is linearly decreasing in magnitude with an increase in
temperature. In contrast, the heat capacities of COOH and COONa groups in aqueous
solution are negative at room temperature and their magnitude non-linearly
decreases with an increase in temperature. It appears that the partial heat
capacity of CONH group in aqueous solution depends on the type of model compound
used for its determination. These differences correlate with the difference in
the water accessible surface area of atoms in the CONH group in different model
compounds.
PMID- 17029832
TI - Significant discrepancies between van't Hoff and calorimetric enthalpies. III.
AB - The study of a wide variety of reversible reactions in solution indicates that
the enthalpy, DeltaH(vH), which controls the temperature variation of the
equilibrium constant for a reaction, can seldom, if ever, be taken to be
independent of the temperature. It is also found in most cases that the values
for DeltaH(vH), properly evaluated as varying with the temperature, differ
significantly from the values for the enthalpy, DeltaH(cal), determined by direct
calorimetry under the same experimental conditions. In a continuing search for
reactions which show agreement between DeltaH(vH) and DeltaH(cal), we have
studied by isothermal titration calorimetry the reactions of heptylamine with
heptanoic acid in dodecane solution and of alpha-cyclodextrin with sodium
heptanoate in aqueous solution.
PMID- 17029833
TI - Competitive electrostatic binding of charged ligands to polyelectrolytes:
practical approach using the non-linear Poisson-Boltzmann equation.
AB - We have developed a practical analytical treatment of the non-linear Poisson
Boltzmann (P-B) equation to characterize the strong but non-specific binding of
charged ligands to DNA and other highly charged macromolecules. These reactions
are notable for their strong salt dependence and anti-cooperativity, features
which the theory fully explains. We summarize analytical results for
concentration profiles and ion binding in various regimes of surface curvature
and ionic strength, and show how counterion size and charge distribution may
influence competitive binding. We present several practical applications of the
formalism, showing how to estimate the ligand concentration needed to effectively
compete with a given buffer salt, and how to calculate the amounts of counterion
species bound at various distances from the DNA surface under given bulk solution
conditions. We cast our results into the form of a Scatchard binding isotherm,
showing how the apparent binding constant K(obs) and S = -dlog K (obs )d log[M
(+)] can be predicted from the basic theory. Anti-cooperativity arises naturally
without steric repulsion, and binding curves can be fitted with K(obs) and
effective charge as the only free parameters. We extend the analytical P-B
analysis to an arbitrary number of counterion species, and apply the results to
fit and predict three-ion competition data.
PMID- 17029834
TI - Thermodynamics of protein unfolding: questions pertinent to testing the validity
of the two-state model.
AB - We discuss a number of questions pertaining to the analysis of data to extract
thermodynamic parameters for the reversible unfolding of proteins. Simulations
are presented to illustrate problems in trying to test the validity of the two
state model, vis-a-vis a more complicated unfolding model. A conceptual and
practical problem is how to consider the unfolded state and how to relate the
observed signal to this state. We discuss the idea that the unfolded state can be
described as a single macrostate, comprising a distribution of microstates having
different degrees of solvent-accessible surface area. We also discuss the
possibilities and thermodynamic consequences of having more than one unfolded
state and of having a denaturant which both stabilizes and destabilizes the
protein's native state.
PMID- 17029835
TI - Neutrophil dysfunction after biomaterial contact in an in vitro model of
cardiopulmonary bypass.
AB - OBJECTIVE: Cardiopulmonary bypass (CPB) induces neutrophil degranulation and
superoxide anion production in vivo. We hypothesized that CPB-associated
neutrophil dysregulation alters neutrophil adhesion to vascular endothelial cells
and the extracellular matrix. METHODS: We, therefore, recirculated neutrophils in
polyvinyl chloride (PVC) tubing using a roller pump model and thereafter measured
adhesion to cultured microvascular endothelial cells and gelatin-coated surfaces.
Recirculation-induced neutrophil priming or exhaustion was tested by boosting
with phorbol myristate-acetate (PMA) or N-formyl-methiolyl-leucyl-phenylalanine
(FMLP) before quantification of adhesion. RESULTS AND CONCLUSION: After
recirculation, neutrophils retained their adhesive capability to vascular
endothelial cells, whereas adhesion to gelatin increased. This increase was not
seen when the neutrophils were recirculated with a rotator instead of a roller
pump, indicating that not only the pump mode but also foreign surface contact was
of significance. The neutrophil PMA response after recirculation was not altered
compared to resting neutrophils prestimulated with PMA. Recirculated neutrophils
adhered less to cultured vascular endothelial cells after FMLP activation and
more to gelatin compared to resting neutrophils prestimulated with FMLP. It is
conceivable that dysregulation of neutrophil adhesive capability may play a part
in the development of tissue damage after CPB.
PMID- 17029836
TI - Estrus behavior and fecal steroid profiles in the Asiatic lion (Panthera leo
persica) during natural and gonadotropin-induced estrus.
AB - In this paper the behavior of the Asiatic lion was studied during natural and
gonadotropin-induced estrus in relation to fecal estradiol and progesterone
concentration. The average length of estrus was 5.4 days and no significant
difference was observed between natural and gonadotropin-induced estrus.
Vocalization and rolling were the major estrus behavioral activities of Asiatic
lions and the frequency of these activities were similar in both natural and
gonadotropin-induced estrus and treatment with exogenous gonadotropin did not
alter estrus behavioral activities. A significant positive correlation was
observed between fecal estradiol and frequency of estrus behavior during natural
and gonadotropin-induced estrus. Following gonadotropin treatment estrus could be
induced in 69% of animals and these induced animals ovulated following hCG
treatment. This study reports for the first time the successful use of the non
invasive fecal steroid assay for monitoring the induction of estrus and ovulation
in the Asiatic lion.
PMID- 17029837
TI - Protein machine model of enzymatic reactions gated by enzyme internal dynamics.
AB - The slow character of conformational transition dynamics in native proteins,
recently becoming more and more apparent, makes conventional theories of chemical
reactions inapplicable for the description of enzymatic reactions. Any
contemporary statistical theory of biochemical processes has to be based on a
possibly simple but realistic model of microscopic dynamics of participating
biomolecules. In a model considered in this paper the dynamics of enzymatic
protein is approximated by a quasi-continuous diffusive motion of its solid-like
structural elements relative to each other. The enzymatic reaction is assumed to
involve three steps (a covalent tranformation preceded and followed by
association-dissociation processes with the substrate and the product), each step
being gated by conformational diffusion. In general, the reaction proceeds in
three stages: initial, transient and steady-state. Carefully approximated
analytical formulae describing the kinetics in each stage are derived. In the
limit of the fast internal dynamics of the enzyme, when compared to the local
chemical transformations, the initial stage of reaction, dependent on the initial
distribution of enzyme conformations, is absent and all the formulae describing
the remaining two stages simplify to those provided by the classical theory of
Haldane. However, following recent studies, the rule seems to be that it is the
conformational dynamics of the enzyme, and not the details of chemical mechanism,
that affects the rate of enzymatic reaction. Apart from the possibility of the
initial inhomogeneous kinetics, the important result obtained in the limit of
slow conformational dynamics is that the kinetic mechanisms of a reaction differ
in general between the transient and steady-state stages. Possibilities of
carrying out an experimentum crucis directly discrediting the conventional
approach are considered.
PMID- 17029838
TI - New method for incorporating solvent influence into the evaluation of X-ray
scattering intensity of proteins in solution.
AB - A new method, the surface integration method, is presented for taking into
account the influence of solvent on the intensity of X-ray scattered from
proteins in solution. It requires no averaging numerically over the solute
orientation. The solvent is modeled by a continuous medium with electrons of
uniform density. This method is applied to amino acids, peptides and native
proteins to confirm its effectiveness. The solvent influence on the normalized
scattering intensity I(K) I(0) is more noticeable for larger solutes and at
larger scattering angles, where I(K) is the intensity of scattered X-ray with the
magnitude of scattering vector K.
PMID- 17029839
TI - Fluorescence and binding properties of phenazine derivatives in complexes with
polynucleotides of various base compositions and secondary structures.
AB - The interactions of two phenazine derivatives, one with a neutral chromophore
(glycoside) and the other with a cationic one (quaternary salt), with various
synthetic single- and double-stranded polynucleotides and natural DNA were
studied by fluorescence techniques, conducting measurements of steady-state
fluorescence intensity and polarization degree as well as fluorescence lifetime.
These dyes show fluorescence quenching upon intercalation into the GC sequences
of the double-stranded nucleic acids and an increase in fluorescence emission and
lifetime upon incorporation into the AT and AU sequences. GC base pairs in
continuous deoxynucleotide sequences were found to be preferred as binding sites
for both phenazines, in contrast to AT base pairs. On the contrary, the
continuous ribonucleotide GC sequence binds the phenazines more weakly than does
the AU sequence. With regard to the interaction of the phenazines with single
stranded polynucleotides, a stacking interaction of the dye chromophores with the
nucleic bases was observed. In that case the guanine residue quenches the
cationic phenazine fluorescence, while the stacking interaction with the other
bases results in an increase in the fluorescence quantum yield. Unlike the
cationic dye, the fluorescence of the neutral phenazine was quenched by both
purine bases.
PMID- 17029840
TI - Secondary solvent effects on the circular dichroism spectra of polypeptides in
non-aqueous environments: influence of polarisation effects on the far
ultraviolet spectra of alamethicin.
AB - Secondary solvent effects on the far ultraviolet circular dichroism spectra of
the polypeptide alamethicin have been studied systematically in a series of
alcohols. The magnitudes of the shifts have been correlated with the physical
properties of the solvents in an attempt to discover the underlying physical
principles responsible for these shifts. The solvent effect in non-aqueous
solvents generally produces spectral transitions with peaks found at longer
wavelengths than those in aqueous solution, and is correlated with increasing
refractive indices and with decreasing dielectric constants of the solvents. It
appears that polarisation effects are the major contributors to the interactions
between the chromophore and solvent molecules, and hence give rise to the red
shift. It is clear that this secondary solvent effect is an important factor
which should be considered in the examination and estimation of polypeptide
secondary structures in non-aqueous solvents and membranes.
PMID- 17029841
TI - Antinociceptive activity of Amazonian Copaiba oils.
AB - Copaiba oil resins are extensively commercialized in Brazil as capsules or crude
oil and used as anti-inflammatory and anti-septic. Comparative pharmacological
studies between different species of Copaiba oils are scarce. In the present work
we compared the antinociceptive activity of two Amazonian Copaiba oils (Copaifera
multijuga Hayne and Copaifera reticulata Ducke, Fabaceae) administered by oral
route using peripheral (acetic acid-induced abdominal writhing and formalin),
spinal (tail flick) and supra-spinal (hot plate) models. Results demonstrated
that the Copaiba oils did not develop toxic effects. Doses ranging from 30 to 150
mg/kg were enough to significantly develop peripheral antinociceptive effect. All
Copaiba oils demonstrate central activity but with less effect on supra-spinal
regions of the brain. Administration of the opioid receptor antagonist, naloxone
completely inhibited the antinociceptive effect induced by both Copaiba oils. Our
results indicate that Copaiba oils demonstrate peripheral and central
antinociceptive effect. This new comprobate effect may be useful in the treatment
of algesic disorders.
PMID- 17029842
TI - AUTO3DEM--an automated and high throughput program for image reconstruction of
icosahedral particles.
AB - AUTO3DEM is an automation system designed to accelerate the computationally
intensive process of three-dimensional structure determination from images of
vitrified icosahedral virus particles. With minimal user input and intervention,
AUTO3DEM manages the flow of data between the major image reconstruction
programs, monitors the progress of the computations, and intelligently updates
the input parameters as the resolution of the model is improved. It is designed
to be used on any computer running the Linux or UNIX operating systems and can be
run in parallel mode on multi-processor systems.
PMID- 17029843
TI - SCA: symmetry-based center assignment of 2D projections of symmetric 3D objects.
AB - A method for finding the center of cryo-EM images which correspond to the
projections of a symmetric 3D structure, based on mathematical properties of
symmetry adapted functions and the Fourier-Bessel transform, is presented. It is
a model independent one-step procedure with no parameters to be chosen by the
user. The proposed method is tested in one synthetic tetrahedral case with
different noise levels and in two real cases with D7 and icosahedral symmetries.
PMID- 17029844
TI - Structure and thermodynamics of the tubulin-stathmin interaction.
AB - Oncoprotein 18/stathmin (stathmin) is a phosphorylation-controlled key regulator
of microtubule dynamics. In recent years, substantial efforts were undertaken to
characterize the complex formed between tubulin and the intrinsically disordered
stathmin molecule. Here, I summarize and illustrate the current structural and
thermodynamic studies on the tubulin-stathmin interaction. Based on these and on
functional information I formulate an updated molecular mechanism on how tubulin
binding by stathmin regulates microtubule dynamics.
PMID- 17029845
TI - Ab initio resolution measurement for single particle structures.
AB - A computational method is described that allows the measurement of the signal-to
noise ratio and resolution of a three-dimensional structure obtained by single
particle electron microscopy and reconstruction. The method does not rely on the
availability of the original image data or the calculation of several structures
from different parts of the data that are needed for the commonly used Fourier
Shell Correlation criterion. Instead, the correlation between neighboring Fourier
pixels is calculated and used to distinguish signal from noise. The new method
has been conveniently implemented in a computer program called RMEASURE and is
available to the microscopy community.
PMID- 17029846
TI - Flap opening dynamics in HIV-1 protease explored with a coarse-grained model.
AB - We present a one-bead coarse-grained model that enables dynamical simulations of
proteins on the time scale of tens of microseconds. The parameterization of the
force field includes accurate conformational terms that allow for fast and
reliable exploration of the configurational space. The model is applied to the
dynamics of flap opening in HIV-1 protease. The experimental structure of the
recently crystallized semi-open conformation of HIV-1 protease is well reproduced
in the simulation, which supports the accuracy of our model. Thanks to very long
simulations and extensive sampling of opening and closing events, we also
investigate the thermodynamics and kinetics of the opening process. We have shown
that the effect of the solvent slows down the dynamics to the experimentally
observed time scales. The model is found to be reliable for application to
substrate docking simulations, which are currently in progress.
PMID- 17029847
TI - Multi-resolution anchor-point registration of biomolecular assemblies and their
components.
AB - An atomic scale interpretation facilitates the assignment of functional
properties to 3D reconstructions of macromolecular assemblies in electron
microscopy (EM). Such a high-resolution interpretation is typically achieved by
docking the known atomic structures of components into the volumetric EM maps.
Docking locations are often determined by maximizing the cross-correlation
coefficient of the two objects in a slow, exhaustive search. If time is of
essence, such as in related visualization and image processing fields, the
matching of data is accelerated by incorporating feature points that form a
compact description of 3D objects. The complexity reduction afforded by the
feature point representation enables a near-instantaneous matching. We show that
such reduced matching can also deliver robust and accurate results in the
presence of noise or artifacts. We therefore propose a novel multi-resolution
registration technique employing feature-based shape descriptions of the
volumetric and structural data. The pattern-matching algorithm carries out a
hierarchical alignment of the point sets generated by vector quantization. The
search-space complexity is reduced by an integrated tree-pruning technique, which
permits the detection of subunits in large macromolecular assemblies in real
time. The efficiency and accuracy of the novel algorithm are validated on a
standard test system of homo-oligomeric assemblies.
PMID- 17029848
TI - Conformational analysis of Amphotericin B.
AB - Within a theoretical approach to the problem of antifungal action of Amphotericin
B (AmB), a conformational analysis of the neutral and zwitterionic form of this
antibiotic in vacuo was performed by the MM2P and AM1 methods. The analysis was
carried out with regard to the mutual orientation of the macrolidic and
glycosidic fragments of the molecule, which is defined by the phi and psi steric
angles. This orientation defines the overall shape of the molecule and is
postulated to be important for the antifungal action of the drug. As a result of
the MM2P calculations, phi, psi steric energy and population maps were prepared.
Several conformers were found on these maps but only two of them (one each for
the zwitterionic and the neutral forms of the antibiotic) were previously
observed experimentally for isolated molecules. Our other calculated conformers
were not observed experimentally but we propose that they may also appear in the
AmB channel structure. The results of our conformational analysis were compared
with experimental NMR data (nuclear Overhauser effects between selected hydrogen
atoms) obtained previously. New structural information obtained for AmB in the
present work will be useful for building a molecular model of AmB-target
interactions as well as for designing new derivatives of AmB.
PMID- 17029849
TI - A theory on the instability of tubular membranes to the periodic conformation by
laser tweezers.
AB - A mechanical theory to analyze the stability of tubular membranes perturbed by
optical tweezers is proposed. I assume that the optical tweezers cause the
temporal elevation of hydrostatic pressure inside tubular membranes due to the
thermal expansion of solvent water, and I relaxed the conservation of volume per
unit length which was strictly maintained in old theories based on the well-known
Rayleigh instability. The mechanical energy composed of bending rigidity,
interfacial tension, and hydrostatic pressure terms can explain the condition of
the previously observed peristaltic and pearling instability. The spontaneous
curvature of the membrane is postulated in the theory. The enhanced pressure
causes the tubules to enter a peristaltic state with a spinodal line in the phase
diagram.
PMID- 17029850
TI - Finite one-dimensional spin systems as models of biopolymers.
AB - New models are proposed for describing various properties of biopolymers,
especially those of proteins and nucleic acids. Each model is constituted of a
set of spins arranged on a chain, and each pair of spins produces an interaction.
We examine the transitions of these spin systems between the ground state and the
disordered state. It is found that the transitions of the present spin systems
demonstrate various properties in response to values of the so-called interaction
energy. If we define interaction energy parameters with no so-called frustration,
the system exhibits two-state transitions, similar to the folding-unfolding
transition of small proteins. The addition of frustrations to the model produces
effects similar to those of mutations in proteins. On the other hand, if the
interactions between two spins attenuate as a function of their separation along
the chain, the transition of the system has characteristics similar to those of
nucleic acids. Thus, the present spin systems can offer a unified view of the
folding-unfolding transition of biopolymers in terms of differences in the
pairwise interactions between spins. Based on our models, we propose a condition
for two-state transition behavior for proteins.
PMID- 17029851
TI - Steady state approximation in the minimal model of the alternative pathway of
complement.
AB - Complement is a response mechanism of the immune system. Two initiation pathways
have been characterized for complement. The classical pathway is antibody
mediated while the alternative pathway is not. Since the alternative pathway is
independent of antibodies, it is always active. For the alternative pathway we
have previously developed a minimal model. Using parameters within physiological
bounds, the model showed complex behavior also within physiological bounds. Thus
the model seems to be an appropriate representation of the alternative pathway
response. By applying a steady state assumption to the Michaelis Menten step of
the minimal model, we reduce the number of variables from six to five. A
comparison between the dynamics of the minimal and contracted models reveals that
the two descriptions may not be compatible. Although both systems show chaotic
behavior it occurs in different regions of parameter space.
PMID- 17029852
TI - Photoelectric properties of chlorophyll and carotene solutions in nematic liquid
crystal located between semiconducting electrodes.
AB - The photopotential and photocurrent generation for chlorophyll a, beta-carotene
and a mixture of these pigments dissolved in nematic liquid crystal and located
between transparent semiconducting electrodes were measured. Both pigments
exhibit photopotential and photocurrent generation. From the photocurrent
amplitudes it follows that the efficiency of electron transfer to a
semiconducting electrode from beta-carotene is higher than from chlorophyll
alpha. The photocurrent amplitude of the pigment mixture is slightly lower than
that calculated as a sum of amplitudes of pigments located in separated cells.
This difference can be explained by secondary effects, such as competition
between carotene and chlorophyll molecules in a process of adsorption on a
semiconducting electrode. Therefore it seems that no charge transfer complexes of
chlorophyll and carotene are formed in the investigated model system.
PMID- 17029853
TI - Mixed-mode oscillations in a self-replicating dimerization mechanism.
AB - Recently, self-replicating molecules have been synthesized in the laboratory by
Rebek. Given the importance of such molecules, we proposed a simple model of a
self-replicating dimer, which works as a template for its own formation. Here we
consider a three variable model. For the model, we obtain mixed-mode and chaotic
oscillations. Also, we find coexistence between two periodic attractors as well
as a periodic and a chaotic attractor.
PMID- 17029854
TI - A pulsed field gradient NMR study of the aggregation and hydration of
parvalbumin.
AB - Pulsed field gradient NMR is a convenient alternative to traditional methods for
measuring diffusion of biological macromolecules. In the present study, pulsed
field gradient NMR was used to study the effects of calcium binding and hydration
on carp parvalbumin. Carp parvalbumin is known to undergo large changes in
tertiary structure with calcium loading. The diffusion coefficient is a sensitive
guide to changes in molecular shape and in the present study the large changes in
tertiary structure were clearly reflected in the measured diffusion coefficient
upon calcium loading. The (monomeric) calcium-loaded form had a diffusion
coefficient of 1.4 x 10(-10) m(2) s(-1) at 298 K, which conforms with the
structure being a nearly spherical prolate ellipsoid from X-ray studies. The
calcium-free form had a significantly lower diffusion coefficient of 1.1 x 10(
10) m(2) s(-1). The simplest explanation consistent with the change in diffusion
coefficient is that the parvalbumin molecules form dimers upon the removal of
Ca(2+) at the protein concentration studied (1 mM).
PMID- 17029855
TI - pK(a) calculations along a bacteriorhodopsin molecular dynamics trajectory.
AB - Electrostatic calculations of pK(a-values) are reported along a 400 ps molecular
dynamics trajectory of bacteriorhodopsin. The sensitivity of calculated pK(a)
values to a number of structural factors and factors related to the modelling of
the electrostatics are also studied. The results are very sensitive to the choice
of internal dielectric constant of the protein (in the interval 2-4). Moreover it
is important to include internal water molecules and to average over a long
enough portion ( approximately 100 ps) of an equilibrium molecular dynamics
trajectory. The internal waters are necessary to get an ion-counter ion complex
with the Schiff base and Arg 82 protonated and the aspartic groups (85 and 212)
deprotonated. The fluctuations along the MD-trajectory do not change the
protonation state of internal residues at neutral pH. However, at other pH values
the averaging along a trajectory maybe crucial to get correct protonation states.
A relationship is found between the arginine group 82, the aspartic group 85 and
the glutamate group 204. Glu 204 is protonated in the ground state but the pK(a)
value decreases towards deprotonation when the chromophore isomerizes into the
cis state.
PMID- 17029856
TI - Kinetic model for carbon partitioning in Solanum tuberosum tubers stored at 2
degrees C and the mechanism for low temperature stress-induced accumulation of
reducing sugars.
AB - Exposure to low but nonfreezing temperatures induces the breakdown of starch and
the accumulation of sucrose, glucose and fructose in potato tubers, a complex
phenomenon known as low-temperature sweetening (LTS). A kinetic model for the
degradation of starch to sucrose, fructose, glucose, hexose phosphates and carbon
dioxide in 2 degrees C-stored mature Solanum tuberosum cv. Norchip (LTS
sensitive) and Solanum tuberosum seedlling ND860-2 (LTS-tolerant) tubers is
presented in this work. Analysis of sugar accumulation data in tubers grown in
1993 and 1994 showed no significant differences in the rates of conversion of
starch to hexose phosphates and hexose phosphates to sucrose for both cultivars
(P > 0.05). The rate constant corresponding to invertase activity was 2.3 day(-1)
for Norchip tubers and 1.1 day(-1) for ND860-2 tubers grown in 1993 (P < or =
0.05); however, no significant differences were observed in invertase activity
for 1994-grown tubers (P > 0.05). The accumulation of the reducing sugars
fructose and glucose was found to be dependent on the relative difference in rate
constants corresponding to invertase activity and glycolytic/respiratory
capacity. This difference was 3-4 fold greater for Norchip in 1993, and 4-6 fold
greater for Norchip in 1994, than for ND860-2 (P < or = 0.05). Results from the
analysis also suggest that the amount of available starch for degradation was
greater in Norchip tubers than ND860-2 tubers (P < or = 0.05). Our analysis
suggests that tubers with decreased invertase activity coupled to increased
glycolytic/respiratory capacity should be more tolerant to low-temperature
stress.
PMID- 17029857
TI - Resolving multiple protein conformers in equilibrium unfolding reactions: a time
resolved emission spectroscopic (TRES) study of Azurin.
AB - Unlike steady-state spectrofluorimetry, time-resolved emission spectroscopy
(TRES) can resolve emissions from fluorophores with similar quantum yields and
overlapping steady-state emission spectra. Time-resolved emission studies of the
protein-intrinsic fluorophore, tryptophan (Trp), can thus potentially be used to
examine protein conformational heterogeneity in solution, as well as to
investigate the existence of populated intermediate structural states in
equilibrium unfolding reactions of single-tryptophan proteins. Here, the single
Trp copper protein, azurin, is examined in various concentrations of guanidine
hydrochloride (GdnCl) with its disulphide bond in an intact state. Interestingly,
multiple envelopes of Trp emission are observed in all TRES spectra acquired,
instead of just two emission envelopes (corresponding to the native and unfolded
states) expected from two-state unfolding. These envelopes appear to be centred
around the same set of emission wavelengths in different TRES spectra, and only
intensities and decay rates vary with the concentration of denaturant used. This
suggests that structural states representing different levels of exposure of Trp
to the aqueous solvent might, in fact, be populated at equilibrium during the
unfolding of azurin by GdnCl.
PMID- 17029858
TI - Osmotic stress induces a phase transition from interdigitated gel phase to
bilayer gel phase in multilamellar vesicles of dihexadecylphosphatidylcholine.
AB - We have investigated the effects of poly(ethylene glycol) (PEG) on the structure
and phase behavior of multilamellar vesicles of dihexadecylphosphatidylcholine
(DHPC-MLVs) using an X-ray diffraction method. At low concentrations of PEG-6K
(MW = 7500), DHPC-MLVs were in an interdigitated gel (L(beta)I) phase, a gel
phase with interdigitated hydrocarbon chains. At around 24% (w/v) PEG 6K, a phase
transition from the L(beta)I phase to a bilayer gel phase occurred in the DHPC
MLVs, and above this concentration, they were in a bilayer gel phase. On the
other hand, ethylene glycol (EG), the monomer of PEG, did not induce this phase
transition in the DHPC-MLVs. A mechanism of this phase transition is proposed and
discussed; a decrease in the repulsive interaction between the head groups of the
phospholipids in the bilayer gel phase with an increase in PEG concentration,
which is due to a decrease in the cross-sectional area of the head group region
by osmotic stress, may be the main reason for this phase transition.
PMID- 17029859
TI - Forensic odontologists successfully identify tsunami victims in Phuket, Thailand.
AB - More than a year has elapsed since the seaquake in South-East Asia in December
2004, and more than 92% of the non-Thai victims have been identified. About 80%
of the non-Thai victims were identified by dental information. This high success
rate of dental identification in Thailand was a matter of surprise for many
forensic experts. Identification based on dental information is a highly
efficient, reliable and rapid procedure. The conclusions drawn from the
identification of tsunami victims in Thailand were recently discussed at the 17th
Meeting of the Standing Committee on Disaster Victim Identification of Interpol
in Lyon, and may be used to formulate new guidelines for the identification of
victims.
PMID- 17029860
TI - The chronology of third molar mineralization in the Austrian population--a
contribution to forensic age estimation.
AB - The aim of the present study was to determine the chronology of third molar
mineralization and to establish Austrian reference data. Therefore, a cross
sectional study was undertaken by evaluating 610 panoramic radiographs in order
to assess the mineralization status of the mandibular third molars of Austrian
male and female individuals (275 males and 335 females) between the ages of 12
and 24. The evaluation was carried out using the eight grade scheme of Demirjian
et al. (1973). Mean ages, standard deviations, standard errors and percentile
distributions are presented for each stage of development. Significant
differences between the left and right mandibular third molars were not found.
Males reach the developmental stages earlier than females, statistically
significant differences were noted in stages E and F. Both mandibular third
molars were observed in the majority of the individuals of the Austrian sample
(477 individuals, 78.2%). For medicolegal purposes the likelihood of whether an
Austrian individual is older than 18 years or not was determined.
PMID- 17029861
TI - Handling manipulated evidence.
AB - Bayesian Networks have been advocated as useful tools to describe the relations
of dependence/independence among random variables and relevant hypotheses in a
crime case. Moreover, they have been applied to help the investigator structure
the problem and evaluate the impact of the observed evidence, typically with
respect to the hypothesis of guilt of a suspect. In this paper we describe a
model to handle the possibility that one or more pieces of evidence have been
manipulated in order to mislead the investigations. This method is based on
causal inference models, although it is developed in a different, specific
framework.
PMID- 17029862
TI - Kinematic, kinetic and EMG patterns during downward squatting.
AB - The aim of this study was to investigate the kinematic, kinetic, and
electromyographic pattern before, during and after downward squatting when the
trunk movement is restricted in the sagittal plane. Eight healthy subjects
performed downward squatting at two different positions, semisquatting (40
degrees knee flexion) and half squatting (70 degrees knee flexion).
Electromyographic responses of the vastus medialis oblique, vastus medialis
longus, rectus femoris, vastus lateralis, biceps femoris, semitendineous,
gastrocnemius lateralis, and tibialis anterior were recorded. The kinematics of
the major joints were reconstructed using an optoelectronic system. The center of
pressure (COP) was obtained using data collected from one force plate, and the
ankle and knee joint torques were calculated using inverse dynamics. In the
upright position there were small changes in the COP and in the knee and ankle
joint torques. The tibialis anterior provoked the disruption of this upright
position initiating the squat. During the acceleration phase of the squat the COP
moved posteriorly, the knee joint torque remained in flexion and there was no
measurable muscle activation. As the body went into the deceleration phase, the
knee joint torque increased towards extension with major muscle activities being
observed in the four heads of the quadriceps. Understanding these kinematic,
kinetic and EMG strategies before, during and after the squat is expected to be
beneficial to practitioners for utilizing squatting as a task for improving motor
function.
PMID- 17029863
TI - Control of head stability during gait initiation in young and older women.
AB - Transition tasks between static and dynamic situations may challenge head
stabilization and balance in older individuals. The study was designed to
investigate differences between young and older women in the upper body motion
during the voluntary task of gait initiation. Seven young (25+/-2.3 years) and
seven older healthy women (78+/-3.4 years) were required to stand on a force
platform and initiate walking at their self-selected preferred speed. Angles of
head, neck and trunk were measured by motion analysis in the sagittal plane and a
cross-correlation analysis was performed on segments pairs. Variability of head
and neck angular displacements, as indicated by average standard deviation, was
significantly greater in the older than in the young participants. The young
women maintained dynamic stability of the upper body, as forward flexion of the
trunk was consistently counteracted by coordinated head-neck extension.
Differently, movement patterns employed by the older women also included a rigid
motion of all upper body segments leaning forward as a single unit. These results
demonstrated that older women perform the transition from standing to walking
with greater variability in the patterns of upper body motion compared to young
women.
PMID- 17029864
TI - Cancer survivors information seeking behaviors: a comparison of survivors who do
and do not seek information about cancer.
AB - OBJECTIVE: To examine the cancer information seeking behaviors and preferences of
cancer survivors. METHODS: This cross-sectional study used the National Cancer
Institute's 2003 Health Information National Trends Survey data to evaluate 619
cancer survivors. RESULTS: Two-thirds (67.5%, n = 418) of the survivors sought
cancer information (InfoSeek) and 32.5% (n = 201) did not (NoInfoSeek).
Significant predictors of cancer information seeking included age (less than 65),
gender (female), income (>US$ 25,000/year), and having a regular health care
provider (HCP). CONCLUSION: Not all survivors actively look for cancer
information. Although most survivors prefer receiving cancer information from
their HCP, many turn to a variety of other sources, primarily the Internet.
PRACTICE IMPLICATIONS: HCPs should periodically assess information seeking
behaviors and preferences of cancer survivors and actively refer patients to the
Internet as an extension of and enhancement to their patient interactions.
Credible and useful websites could be identified and recommended by the HCP as a
means to address some of the barriers identified by survivors.
PMID- 17029866
TI - Physico-chemical properties of the heat-induced 'superaggregates' of amphotericin
B.
AB - The aggregation state of amphotericin B (AmB) was previously reported to modulate
its therapeutic efficiency. As a preliminary study to test the biological effects
of 'superaggregates' generated by heat treatment, we present spectroscopic data
related to their formation in aqueous solutions. Drastic changes in the AmB
aggregation state in water were shown to occur on heating at 50-60 degrees C. The
concentration of the aggregates formed at high (A(t)) or room (A) temperature,
and the concentration of the monomeric form (M) of AmB were calculated by
processing absorption data. The thermally induced conversion from A to A(t)
depends on the AmB concentration. Rayleigh scattering measurements suggest that
the A(t) aggregates are larger than the A aggregates. At room temperature, the
condensation rate of A with M-leading to the 'superaggregated' form A(t)-was
slower and depended on the concentration of M. The superaggregated species A(t)
was shown to be the most chemically stable species. Physico-chemical properties
of these superaggregates are discussed as a potential new solution to improve the
therapeutic efficacy of AmB.
PMID- 17029865
TI - Voluntary counseling and testing among post-partum women in Botswana.
AB - OBJECTIVE: To determine uptake and socio-demographics predictors of acceptance of
voluntary counseling and testing (VCT) among post-partum women in Botswana.
METHODS: Women attending maternal and child health clinics for their first post
partum or well baby visit in three sites in Botswana were offered VCT after a
written informed consent. A standardized questionnaire was used to collect socio
demographic characteristics and reasons for declining VCT. RESULTS: From March
1999 to November 2000, we approached 1735 post-partum women. Only 937 (54%) of
those approached accepted VCT. In multiple logistic regression analysis, younger
maternal age, not being married, and less formal education were significant
predictors of acceptance of VCT. Thirty percent of women who accepted VCT were
HIV-positive. CONCLUSION: Our results indicated that in Botswana prior to the
initiation of a government Mother to Child Transmission (MTCT) prevention
program, younger, unmarried, and less educated post-partum women were more likely
to undergo VCT. PRACTICE IMPLICATIONS: Our results have shown that interventions
to improve VCT among post-partum women and more generally among women of
reproductive age are warranted in Botswana. These interventions should account
for differences such age, marital status, education, and partner involvement to
maximize VCT uptake.
PMID- 17029867
TI - Complex intracellular calcium oscillations. A theoretical exploration of possible
mechanisms.
AB - Intracellular Ca(2+) oscillations are commonly observed in a large number of cell
types in response to stimulation by an extracellular agonist. In most cell types
the mechanism of regular spiking is well understood and models based on Ca(2+)
induced Ca(2+) release (CICR) can account for many experimental observations.
However, cells do not always exhibit simple Ca(2+) oscillations. In response to
given agonists, some cells show more complex behaviour in the form of bursting,
i.e. trains of Ca(2+) spikes separated by silent phases. Here we develop several
theoretical models, based on physiologically plausible assumptions, that could
account for complex intracellular Ca(2+) oscillations. The models are all based
on one- or two-pool models based on CICR. We extend these models by (i)
considering the inhibition of the Ca(2+)-release channel on a unique
intracellular store at high cytosolic Ca(2+) concentrations, (ii) taking into
account the Ca(2+)-activated degradation of inositol 1,4,5-trisphosphate (IP(3)),
or (iii) considering explicity the evolution of the Ca(2+) concentration in two
different pools, one sensitive and the other one insensitive to IP(3). Besides
simple periodic oscillations, these three models can all account for more complex
oscillatory behaviour in the form of bursting. Moreover, the model that takes the
kinetics of IP(3) into account shows chaotic behaviour.
PMID- 17029868
TI - Visualization of the chromosome scaffold and intermediates of loop domain
compaction in extracted mitotic cells.
AB - A novel extraction protocol for cells cultured on coverslips is described.
Observations of the extraction process in a perfusion chamber reveal that cells
of all mitotic stages are not detached from coverslips during extraction, and all
stages can be recognized using phase contrast images. We studied the extracted
cell morphology and distribution of a major scaffold component - topoisomerase
IIalpha, in extracted metaphase and anaphase cells. An extraction using 2M NaCl
leads to destruction of chromosomes at the light microscope level. Immunogold
studies demonstrate that the only residual structure observed is an axial
chromosome scaffold that contains topoisomerase IIalpha. In contrast, mitotic
chromosomes are swelled only partially after an extraction using dextran sulphate
and heparin, and it appears that this treatment does not lead to total
destruction of loop domains. In this case, the chromosome scaffold and numerous
structures resembling small rosettes are revealed inside extracted cells. The
rosettes observed condense after addition of Mg2+-ions and do not contain
topoisomerase IIalpha suggesting that these structures correspond to
intermediates of loop domain compaction. We propose a model of chromosome
structure in which the loop domains are condensed into highly regular structures
with rosette organization.
PMID- 17029869
TI - Patients' attitudes to totally implantable venous access port systems for
gynecological or breast malignancies.
AB - AIMS: The aim of this study was to analyze patients' port-related quality of
life. PATIENTS AND METHODS: 260 consecutive patients with gynecological or breast
malignancies were asked to take part in a questionnaire-based survey including 26
questions, and 232 women agreed to participate in the study. The questionnaire
inquired about port-related aspects of everyday life and the use of a central
venous access port device for chemotherapy and supportive cancer care.
Multivariate analysis was used to identify parameters associated with
satisfaction and dissatisfaction in relation to the port. RESULTS: Most of the
women were very satisfied with the use of a port to provide venous access for
chemotherapy and supportive cancer care. Faster hospital procedures, good
cosmetic results, and the ability to cope with the social environment had a
significant influence on the degree of satisfaction. Fear of port punctures,
inconvenient heparinization of the port, and fear of complications were found to
be negative variables associated with the method. CONCLUSIONS: Port catheters are
well accepted by patients for chemotherapy and supportive cancer care. Generally
ports should be rapidly removed after the end of antineoplastic treatment in
order to improve patients' satisfaction with the procedure.
PMID- 17029871
TI - Re: Manfred Eigen's 70th birthday.
PMID- 17029870
TI - Androgens' performance-enhancing effects in the inhibitory avoidance and water
maze tasks may involve actions at intracellular androgen receptors in the dorsal
hippocampus.
AB - Androgens can have performance-enhancing effects in some cognitive tasks, but the
mechanism of these effects has not been established. Experiments examined whether
androgens' actions to bind to intracellular androgen receptors (ARs) in the
hippocampus are necessary to enhance cognitive performance in the inhibitory
avoidance and water maze tasks. If androgens' binding at ARs are essential, then
blocking them through intrahippocampal administration of flutamide, an AR
receptor antagonist, should attenuate androgens' performance-enhancing effects in
the inhibitory avoidance and water maze tasks. In Experiments 1 and 2, flutamide
was administered through intrahippocampal inserts to intact male rats immediately
pre- and post-training in the inhibitory avoidance and water maze tasks. Both pre
and post-training administration of flutamide to the dorsal hippocampus, but not
missed sites, produced significantly poorer performance in the inhibitory
avoidance and water maze tasks, without influencing control measures such as
flinch/jump threshold or swim speed. In Experiment 3, flutamide administration to
the hippocampus was delayed two hours following training in the inhibitory
avoidance and water maze tasks. There was no significant effect of delayed
administration of flutamide on performance in either of these tasks. Together,
these findings suggest that blocking ARs in the dorsal hippocampus with flutamide
administration immediately pre- or post-training can produce decrements in
cognitive performance, which implies that androgens' performance-enhancing
effects may occur, in part, through binding at intracellular androgen receptors
in the dorsal hippocampus.
PMID- 17029872
TI - To Manfred Eigen on his 70th birthday.
PMID- 17029873
TI - Genotypes with phenotypes: adventures in an RNA toy world.
AB - Evolution has created the complexity of the animate world and deciphering the
language of evolution is the key towards understanding nature. The dynamics of
evolution is simplified by considering it as a superposition of three less
sophisticated processes: population dynamics, population support dynamics, and
genotype-phenotype mapping. Evolution of molecules in laboratory assays provides
a sufficiently simple system for the quantitative analysis of the three
phenomena. Coarse-grained notions of structures like RNA secondary structures are
used as model phenotypes. They provide an excellent tool for a comprehensive
analysis of the entire complex of molecular evolution. The mapping from RNA
genotypes into secondary structures is highly redundant. In order to find at
least one sequence for every common structures one need only search a
(relatively) small part of sequence space. The existence of selectively neutral
phenotypes plays an important role for the the success and the efficiency of
evolutionary optimization. Molecular evolution found a highly promising
technological application in the design of biomolecules with predefined
properties.
PMID- 17029874
TI - On the generation of information as motive power for molecular evolution.
AB - Molecular evolution can be described as a learning process during which
previously inanimate matter developed the ability to organize all the reaction
pathways that establish a living system. Common to all natural self-organizing
procedures is the ability of matter to store, process and evaluate the
information achieved by learning. Genetic information which is stored in RNA or
DNA is the object of natural evolution. With the recognition of nature's
concepts, evolutionary optimization was applied to biopolymers that are not
optimally adapted for particular technical or medical purposes. Information can
also be stored in molecules with structures and chemical properties that are
completely different from nucleic acids. Therefore, optimization processes that
mimic the natural evolutionary strategies can also be applied to small organic
molecules. Much effort has been made theoretically and practically to find a
certain optimized species within the (hyper)astronomical number of possible
sequence alternatives. From a series of computer experiments it can be concluded
that it is not necessary to search the entire sequence space in order to find a
particular structure; this is advantageous because the diversity of mutant
libraries that can realistically be achieved in the laboratory never extends to
the number of theoretically possible sequences. Molecular mutant libraries that
serve as starting populations for in vitro selection have been constructed for
nucleic acids, proteins, peptides and small organic molecules.
PMID- 17029875
TI - The role of peptide modules in protein evolution.
AB - Protein evolution shows interesting strategies to be used in protein design.
During evolution the creation of new proteins has been accomplished by combining
different peptide modules, i.e. evolutionary successful stable folding units.
Thereby, the evolution of proteins has been greatly enhanced. Today this
mechanism of recombining optimized building blocks to design new proteins has
been introduced into applied molecular evolution.
PMID- 17029876
TI - Confocal spectroscopy in microstructures.
AB - Confocal instrumentation makes it possible to carry out spectroscopic
measurements with a very high signal-to-background ratio. The transit of a single
fluorescent molecule through the focal point of the light can be monitored with
this method. The particle transport can be observed in transparent microchannels.
Examples of fluorescence correlation spectroscopy and single molecule handling in
microstructures are discussed.
PMID- 17029877
TI - Macrodipoles. Unusual electric properties of biological macromolecules.
AB - The wide range of different effects induced by electric fields in biological
macromolecules is clearly due to the unusual quality and quantity of their
electric parameters. A general concept for a quantitative description of the
polarizability of macromolecules remains to be established. In the case of DNA,
experimental data indicate the existence of an effective polarization length
N(p); at chain lengths N < N(p) the polarizability increases with N(2), whereas
saturation is approached at N > or = N(p). The polarization length decreases with
increasing ionic strength in close analogy to the Debye length, but is
approximately 10 times larger than the Debye length. The dynamics of DNA
polarization at high field strengths has been observed in the ns time range and
is consistent with biased field induced ion dissociation. In the range of chain
lengths from approximately 400 to approximately 850 base pairs DNA molecules
exhibit permanent dipole moments, which are in a preferentially perpendicular
direction to the end-to-end-vector, leading to a positive electric dichroism.
These results are consistent with a "frozen" ensemble of bent DNA configurations
and provide evidence for the existence of slow, non-elastic bending transitions.
The electric parameters of proteins are usually dominated by a permanent
anisotropy of the charge distribution, corresponding to permanent dipole moments
of the order of several hundred Debye up to about 1500 Debye. Relatively small
dipole moments of protein monomers add up to millions of Debye, when these
proteins are in a vectorial organization in membrane patches, as found for
bacteriorhodopsin and Na (+)K (+)-ATPase . In these cases the dipole vector may
support vectorial ion transport. It is remarkable that the dipole moments of
proteins usually show a relatively small dependence on the salt concentration; a
rational for these observations is provided by a dipole potential at the plane of
shear for rotational diffusion, which is defined in close analogy to the zeta
potential for translational diffusion. Symmetry breaking leading to huge electric
dipole moments may be expected for mixed lipid vesicles: according to model
calculations the phase separation of lipid components with and without net
charges may lead to very high dipole moments; the expectation has been verified
experimentally for vesicles containing DMPA and DMPC. The state of these systems
should be extremely sensitive to electric fields. In summary, there is an unusual
wide variation of electric parameters associated with biological macromolecules
and with biomolecular assemblies, which is the basis for the complexity of
different phenomena induced by electric fields in biological systems.
PMID- 17029879
TI - The saphenous veins--great and small or long and short?
PMID- 17029878
TI - Practical PCR tools for the delineation of Contracaecum rudolphii A and
Contracaecum rudolphii B (Ascaridoidea: Anisakidae) using genetic markers in
nuclear ribosomal DNA.
AB - Using genetic markers defined previously in the internal transcribed spacers (ITS
1 and ITS-2) of nuclear ribosomal DNA (rDNA), PCR-coupled restriction fragment
length polymorphism (PCR-RFLP) and specific PCR assays were established for the
specific detection of each of two morphologically indistinguishable operational
taxonomic units (Contracaecum rudolphii A and Contracaecum rudolphii B) within
Contracaecum rudolphii (s.l.) and their differentiation from Contracaecum
septentrionale, a closely related congener. Application of these tools to C.
rudolphii (s.l.) adults from Phalacrocorax carbo sinensis (the Eurasian
subspecies of the great cormorant) from Qinghai Lake in China, revealed C.
rudolphii B to infect this host. This is the first report of C. rudolphii B in P.
carbo sinensis outside of Europe (where it was originally detected), supporting
the proposal that this species has a broad geographical distribution. Together
with other methods, each of these molecular tools will be useful for
investigating the ecology of C. rudolphii A and C. rudolphii B as well as C.
septentrionale.
PMID- 17029880
TI - Colony-stimulating factors in veterinary medicine: an unexplored potential.
PMID- 17029881
TI - Stable concurrent synchronization in dynamic system networks.
AB - In a network of dynamical systems, concurrent synchronization is a regime where
multiple groups of fully synchronized elements coexist. In the brain, concurrent
synchronization may occur at several scales, with multiple "rhythms" interacting
and functional assemblies combining neural oscillators of many different types.
Mathematically, stable concurrent synchronization corresponds to convergence to a
flow-invariant linear subspace of the global state space. We derive a general
condition for such convergence to occur globally and exponentially. We also show
that, under mild conditions, global convergence to a concurrently synchronized
regime is preserved under basic system combinations such as negative feedback or
hierarchies, so that stable concurrently synchronized aggregates of arbitrary
size can be constructed. Robustnesss of stable concurrent synchronization to
variations in individual dynamics is also quantified. Simple applications of
these results to classical questions in systems neuroscience and robotics are
discussed.
PMID- 17029883
TI - Use of multi-coil parallel-gap resonators for co-registration EPR/NMR imaging.
AB - This article reports experimental investigations on the use of RF resonators for
continuous-wave electron paramagnetic resonance (cw-EPR) and proton nuclear
magnetic resonance (NMR) imaging. We developed a composite resonator system with
multi-coil parallel-gap resonators for co-registration EPR/NMR imaging. The
resonance frequencies of each resonator were 21.8MHz for NMR and 670MHz for EPR.
A smaller resonator (22mm in diameter) for use in EPR was placed coaxially in a
larger resonator (40mm in diameter) for use in NMR. RF magnetic fields in the
composite resonator system were visualized by measuring a homogeneous 4-hydroxy
2,2,6,6-tetramethyl-piperidinooxy (4-hydroxy-TEMPO) solution in a test tube. A
phantom of five tubes containing distilled water and 4-hydroxy-TEMPO solution was
also measured to demonstrate the potential usefulness of this composite resonator
system in biomedical science. An image of unpaired electrons was obtained for 4
hydroxy-TEMPO in three tubes, and was successfully mapped on the proton image for
five tubes. Technical problems in the implementation of a composite resonator
system are discussed with regard to co-registration EPR/NMR imaging for animal
experiments.
PMID- 17029884
TI - 13C/14N heteronuclear multiple-quantum correlation with rotary resonance and
REDOR dipolar recoupling.
AB - A two-dimensional (13)C/(14)N heteronuclear multiple quantum correlation (HMQC)
experiment using dipolar recoupling under magic-angle spinning (MAS) is
described. The experiment is an extension of the recent indirect (13)C detection
scheme for measuring (14)N quadrupolar coupling under MAS. The recoupling allows
the direct use of the much larger dipolar interaction instead of the small J and
residual dipolar couplings for establishing (13)C/(14)N correlations. Two
recoupling methods are incorporated into the HMQC sequence, both applying rf only
to the observed (13)C spin. The first one uses the REDOR sequence with two pi
pulses per rotor cycle. The second one uses a cw rf field matching the spinning
frequency, known as rotary resonance. The effects of CSA, T(2)(') signal loss,
MAS frequency and stability and t(1)-noise are compared and discussed.
PMID- 17029886
TI - Elevated serum B-Lymphocyte activating factor (BAFF) in chronic hepatitis C virus
infection: association with autoimmunity.
AB - In this study we aimed to determine whether serum B-lymphocyte activating factor
(BAFF) level is increased in patients with chronic hepatitis C virus (HCV)
infection, and to assess its association with HCV-related autoimmunity. Sixty
five patients with chronic HCV infection were compared with two disease control
groups [57 patients with systemic lupus erythematosus (SLE) and 15 with chronic
hepatitis B virus (HBV) infection] and a healthy control group of 35 individuals.
A special attention was given to HCV-related arthralgia and or vasculitis. Serum
BAFF was assessed in all studied individuals, whereas rheumatoid factor (RF),
anti-cardiolipin antibodies (aCL), and cryoglobulins were determined in HCV and
HBV infected patients, and anti-dsDNA antibodies and aCL were assessed in
patients with SLE. Mean serum BAFF was increased in patients with HCV infection
and SLE (2.4+/-0.8 ng/ml and 3.1+/-1.34 ng/ml respectively) compared to 1.1+/
0.14 ng/ml in patients with HBV; and to 1.1+/-0.27 in healthy controls (all,
p<0.0001). The elevation in serum BAFF was associated with HCV-related arthralgia
and or vasculitis (p<0.0001), and with the presence of aCL and of cryoglobulins.
HBV patients lacked features suggestive of autoimmunity. In SLE patients,
elevated serum BAFF was in association with the presence of anti-dsDNA (p=0.002).
As in other autoimmune diseases, increased serum BAFF was also found in patients
with chronic HCV infection. Elevated serum BAFF levels were associated with
clinical and laboratory features of autoimmunity, suggesting that BAFF may play a
role in HCV-related autoimmunity.
PMID- 17029885
TI - Incomplete penetrance of susceptibility genes for MHC-determined immunoglobulin
deficiencies in monozygotic twins discordant for type 1 diabetes.
AB - Incomplete intrinsic penetrance is the failure of some genetically susceptible
individuals (e.g., monozygotic twins of those who have a trait) to exhibit that
trait. For the first time, we examine penetrance of susceptibility genes for
multiple MHC gene-determined traits in the same subjects. Serum levels of IgA,
IgD, IgG3, but not IgG4, in 50 pairs of monozygotic twins discordant for type 1
diabetes (T1D) correlated more closely in the twins than in random paired
controls. The frequencies of subjects deficient in IgA (6%), IgD (33%) and IgG4
(12%), but not in IgG3, were higher in the twins than in controls. We postulate
that this was because the MHC haplotypes (and possible non-MHC genes) that
predispose to T1D also carry susceptibility genes for certain immunoglobulin
deficiencies. Immunoglobulin deficiencies were not associated with T1D. Pairwise
concordance for the deficiencies in the twins was 50% for IgA, 57% for IgD and
50% for IgG4. There were no significant associations among the specific
immunoglobulin deficiencies except that all IgA-deficient subjects had IgD
deficiency. Thus, intrinsic penetrance is a random process independently
affecting different MHC susceptibility genes. Because multiple different external
triggers would be required to explain the results, differential environmental
determinants appear unlikely.
PMID- 17029887
TI - Evaluation of intrinsic chemical kinetics and transient product spectra from time
resolved spectroscopic data.
AB - This communication is devoted to the evaluation of true spectra and intrinsic
(microscopic) rate constants from apparent kinetics measured in time-resolved
spectroscopic experiments monitoring complex relaxation dynamics of multi
intermediate systems. Retinal proteins, cytochrom c oxidase, phytochrome,
hemoglobin, and photoactive yellow protein are examples of natural systems in
which several transient states (intermediates) overlap so strongly, both in time
and spectral domains, that their isolation and full characterization by classical
biochemical methods is impossible, and mathematical evaluation of their true
spectra and microscopic kinetic constants is required. Most of the popular
methods for analysis of kinetic data, global fitting (GF), singular value
decomposition (SVD), principal component analysis (PCA) and factor analysis (FA),
are applicable to two-dimensional (2D, in time and spectral domains) arrays of
data. All these methods produce only a phenomenological description of data, that
approximates the measured data only with apparent kinetics. A fundamental
limitation, namely, insufficient information in 2D data, does not allow any of
these methods to reach the final goal: to recalculate from apparent to intrinsic
values in any but the most trivial cases. A strategy was proposed (J.F. Nagle,
Biophys. J.. 59 (1991) 476-487) to include an additional (third) information-rich
dimension, temperature, into the simultaneous computer analysis. A simultaneous
direct fitting of 3D data arrays to systems of differential rate equations allows
recalculation of apparent kinetics into true spectra and intrinsic rate
constants. In spite of its evident theoretical advantages, this strategy has not
been successful on real data. Here we describe another custom-built program,
SCHEMEFIT, developed for the same purpose: to fit measured kinetics directly to
the system of coupled differential rate equations describing the photochrome's
relaxation dynamics. Though sharing the main strategy with the previous approach,
SCHEMEFIT is based on a different set of numeric algorithms, and its application
requires different tactics. Its performance is illustrated on synthetic data, and
compared with GF and SVD. An example of applying SCHEMEFIT to the photocycle of
halorhodopsin is also reported.
PMID- 17029888
TI - The self-association of flavin mononucleotide (FMN(2-)) as determined by (1)H NMR
shift measurements.
AB - The concentration dependence of the (1)H NMR chemical upfield shifts of the
protons H6, H9, H7alpha, and H8alpha of the 7,8-dimethylisoalloxazine residue of
flavin mononucleotide (FMN(2-)) has been measured and the self-stacking tendency
of FMN(2-) was quantified with the isodesmic model of indefinite non-cooperative
self-association. The stacking tendency of FMN(2-) is considerable and described
in the concentration range of 0.0025-0.1 M with the indicated model by K = 27 +/-
15 M(-1) (25 degrees C; I = 0.1-0.3 M). This result is compared with related ones
from the literature. The caveats regarding the self-stacking properties of FMN(2
) and their dependence on the concentration are discussed.
PMID- 17029889
TI - Self-sustained pH oscillations in a compartmentalized enzyme reactor system.
AB - This work represents our continued effort toward fulfilling the need to discover
a model system for experimental investigations of temporal oscillations in an
enzyme-membrane system. In this paper, the regions in the parameter space where
self-sustained pH oscillations can be induced for a compartmentalized enzyme
reactor system, which consists of a well-stirred reactor, a reservoir and a
membrane containing no enzyme, were determined via numerical simulation with two
proteolytic enzymes: papain (EC 3.4.22.2) and alpha-chymotrypsin (EC 3.4.21.1).
The sizes of the regions were qualitatively compared with those associated with
enzymic membrane system. As a result, we found that the possibility of
experimentally observing self-sustained oscillations in the compartmentalized
papain reactor system, as well as in the papain-membrane system, is high.
However, self-sustained pH oscillations are less likely in the compartmentalized
alpha-chymotrypsin reactor system than in the alpha-chymotrypsin-membrane system.
PMID- 17029890
TI - Evidence for increased proton dissociation in low-activity forms of
dephosphorylated squash-leaf nitrate reductase.
AB - The pH dependence of squash-leaf nitrate reductase has been studied. It has been
found that high- and low-activity forms of purified nitrate reductase (both forms
dephosphorylated) have different optimum pH values. A high-activity form has
always a higher pH optimum compared with a low-activity form. Model computations
show that the decrease in activity and the corresponding change of the pH optimum
is apparently due to a conformation-dependent increase of proton dissociation of
the enzyme. As previously shown, this behavior is also observed in leaf extracts
during the conversion (and probably phosphorylation of nitrate reductase) from a
high-active form to a low-active form when plants are transferred from light to
darkness.
PMID- 17029891
TI - Electrostatic contribution to the bending of DNA.
AB - A model is derived that accounts for the short-range electrostatic contribution
to the bending of DNA molecule in solution and in complexes with proteins in
terms of the non-linear Poisson-Boltzmann equation. We defined that the short
range electrostatic interactions depend on the changes of the polyion surface
charge density under deformation, while the long-range interactions depend on the
bending-induced changes in distances between each two points along the polyion
axis. After an appropriate simplification of the Poisson-Boltzmann equation, the
short-range term is calculated separately giving the lower limit for the
electrostatic contribution to the DNA persistence length. The result is compared
with the theoretical approaches developed earlier [M. Fixman, J. Chem. Phys. 76
(1982) 6346; M. Le Bret, J. Chem. Phys. 76 (1982) 6243] and with the experimental
data. The conclusion is made that the results of Fixman-Le Bret, which took into
account both types of the electrostatic interactions for a uniformly bent
polyion, give the upper limit for the electrostatic persistence length at low
ionic strength, and the actual behavior of the DNA persistence length lies
between two theoretical limits. Only the short-range term is significant at
moderate-to-high ionic strength where our results coincide with the predictions
of Fixman-Le Bret. The bending of DNA on the protein surface that is accompanied
by an asymmetric neutralization of the DNA charge is also analyzed. In this case,
the electrostatic bending energy gives a significant favorite contribution to the
total bending energy of DNA. Important implications to the mechanisms of DNA
protein interactions, particularly in the nucleosome particle, are discussed.
PMID- 17029892
TI - Activity coefficients of the electrolyte and the amino acid in water + NaNO(3) +
glycine and water + NaCl + DL-methionine systems at 298.15 K.
AB - The activity coefficients at 298.15 K of glycine in water + NaNO(3) + glycine
system and dl-methionine in water + NaCl + dl-methionine system are reported. The
measurements were performed in an electrochemical cell with two ion selective
electrodes, a cation and an anion ion selective electrode, each versus a double
junction reference electrode. The concentrations of the electrolytes and the
amino acids studied covered up to 1.0 molality electrolyte, 2.4 molality glycine
and 0.2 molality dl-methionine. The results of the activity coefficients of
glycine are compared with the activity coefficients of glycine in water + NaCl +
glycine and water + KCl + glycine systems, obtained from the previous studies.
The results show that the nature of both the cation and the anion of an
electrolyte have significant effects on the activity coefficient of glycine in
aqueous electrolyte solutions. The results also show that there are attractive
interactions between the molecules of glycine and NaNO(3) and repulsive
interactions between the molecules of dl-methionine and NaCl.
PMID- 17029893
TI - Length dependence of displacement fluctuations and velocity in microtubule
sliding movement driven by sea urchin sperm outer arm beta dynein in vitro.
AB - We have studied the dependence on microtubule length of sliding velocity and
positional fluctuation from recorded trajectories of microtubules sliding over
sea urchin sperm outer arm beta dynein in a motility assay in vitro. The
positional fluctuation was quantified by calculating the mean-square displacement
deviation from the average, the calculation of which yields an effective
diffusion coefficient. We have found that (1) the sliding velocity depends
hyperbolically on the microtubule length, and (2) the effective diffusion
coefficients do not depend on the length for sufficiently long microtubules. The
length dependence of the sliding velocity indicates that the duty ratio, defined
as the force producing period over the total cycle time of beta dynein
interaction with microtubule, is very small. The length independence of the
effective diffusion coefficient indicates that there is a correlation in the
sliding movement fluctuation of microtubules.
PMID- 17029894
TI - Biphasic transitions of a hairpin hexanucleotide triplex DNA.
AB - The conformational transitions (helix-coil transitions) of three hairpin triple
helices, models 5'-(A-G)(3) + 5'-(T-C)(3)-T(4)-((br)C-T)(3) [CY], 5'-(A-G)(3) +
5'-(T-(br)C)(3)-T(4)-(C-T)(3) [YC] and 5'-(A-G)(3) + 5'-(T-(br)C)(3)-T(4)-((br)C
T)(3) [YY], are characterized in this work by UV spectroscopy. Melting of these
triplexes is biphasic, and the profiles are used to obtain the thermodynamic
parameters. The thermodynamic properties of the hairpin triplex are T(m) = 19.45
degrees C and DeltaH(vH) = 293.12 kJ mol(-1) for CY, T(m) = 22.85 degrees C and
DeltaH(vH) = 256.63 kJ mol(-1) for YC and T(m) = 28.47 degrees C and DeltaH(vH) =
234.68 kJ mol(-1) for YY at pH 4.4. Those of the duplex are T(m) = 30.50 degrees
C and DeltaH(vH) = 427.09 kJ mol(-1) for CY, T(m) = 32.96 degrees C and
DeltaH(vH) = 374.47 kJ mol(-1) for YC and T(m) = 33.24 degrees C and DeltaH(vH) =
329.67 kJ mol(-1) for YY at pH 4.4. The distinct transitions of triplex to duplex
and duplex to single strands are analyzed using the nearest-neighbor Ising model.
Electrostatic effects on each conformation are also analyzed.
PMID- 17029895
TI - Characterization of fluorescence quenching in bifluorophoric protease substrates.
AB - NorFES is a relatively rigid, bent undecapeptide which contains an amino acid
sequence that is recognized by the serine protease elastase (AspAlaIleProNle
downward arrow SerIleProLysGlyTyr ( downward arrow indicates the primary cleavage
site)). Covalent attachment of a fluorophore on each side of NorFES's elastase
cleavage site enables one to use a change of fluorescence intensity as a measure
of enzymatic activity. In this study two bichromophoric NorFES derivatives, D
NorFES-A and D-NorFES-D, were prepared in which D (donor) was
tetramethylrhodamine and A (acceptor) was rhodamine-X, two chromophores with
characteristics suitable for energy transfer. Absorption and fluorescence spectra
were obtained with both the intact and cleaved homodoubly, heterodoubly and
singly labeled derivatives. It was found that both the homo and hetero doubly
labeled derivatives form ground-state complexes which exhibit exciton bands. The
hetero labeled derivative exhibits little or no resonance energy transfer.
Spectral measurements were also done in urea, which partially disrupts ground
state dimers.
PMID- 17029896
TI - Interaction of a G-DNA quadruplex with mono- and divalent cations. A force field
calculation.
AB - The formation and stability of four-stranded DNA in solution is specifically
dependent on the type of cations present. The interaction potential of a model
quadruplex structure with different mono- and divalent ions was determined by
force field calculations. Though the electrostatic contribution to the total
energy is mainly responsible for the stabilisation of the cations within the
quadruplex channel, it is the van der Waals interaction at short distances that
determines the specific characteristics of the different cations. An explicit
consideration of the solvent indicates that the position of water molecules in
close proximity to the DNA channel have a strong influence on the form of the
potential, and hence on the capability of the cations for leaving and re-entering
the cavity. The effect of cation size, as expressed through their Lennard-Jones
parameters, is discussed.
PMID- 17029897
TI - Strong and weak binding of water to proteins studied by NMR triple-quantum
filtered relaxation spectroscopy of (17)O-water.
AB - The triple-quantum filtered (TQF) spin-echo signal of (17)O-water, in the
presence of proteins, was analysed to yield estimates of the number of weakly,
and strongly bound water molecules. The analysis used a constrained direct
iterative regression procedure with a three-state model of fast-exchange. Thus,
the population size of free, weakly, and strongly bound water were determined
simultaneously. The two fractions of the bound water were estimated by using
correlation time(s) estimated in other studies. Bovine serum albumin (BSA), basic
pancreatic trypsin inhibitor (BPTI), lysozyme and oxyhaemoglobin were studied. Of
the four proteins, BSA contained the largest number of strongly and weakly bound
water molecules, there being approximately 30 of the former and approximately
3000 of the latter under conditions of high protein concentration. The
correlation time of the proteins increases with their concentration in solution,
and when this was taken into account for BSA the estimated number of strongly
bound water molecules did not change significantly. This NMR technique, and data
analysis, will probably also be useful in studies of water binding and mobility
in various systems including hydrogels, protein networks, membranes, cells and
tissues.
PMID- 17029898
TI - A quantitative analysis of single protein-ligand complex separation with the
atomic force microscope.
AB - Force measurements on and within single macromolecular complexes utilizing
techniques such as atomic force microscopy, optical trapping, flexible glass
fibers, and magnetic beads provide a rich source of quantitative data on
biomolecular processes. Stochastic thermal fluctuations, an undesirable source of
noise in macroscopic biochemical experiments, are an essential element of these
sensitive and novel experiments. With the proper analysis, a great deal of
information can be gleaned from measurements of these fluctuations. A
quantitative framework for analyzing such measurements, based on Kramers' theory
of molecular dissociation, is developed. The analysis reveals the kinetic origin
and stochastic nature of the measurements. This framework is presented in the
context of protein-ligand separation with the atomic force microscope.
PMID- 17029899
TI - Free energy of the binding of uridylic acid oligomers with double stranded
poly(A) x poly(U).
AB - The binding parameters (K, omega) and the free energy (DeltaG(0)) of triple helix
formation have been estimated for complexes of oligo(U)(n) (n = 5, 7-10) with
poly(A) . poly(U) on the basis of hypochromicity measurements. The data were
treated according to the formula of McGhee and von Hippel [J. Mol. Biol. 86
(1974) 469] by a computer program ALAU [H. Schutz et al., Stud. Biophys. 104
(1984) 23] which takes absorbancies and total concentrations as input. In 1 mM
cacodylate buffer pH 7.0 with 10 mM NaCl and 10 mM MgCl(2) at 5 degrees C the
free energy of contiguous binding was found to be a linear function of the
oligomer length with a slope of DeltaG(c,U)(0) = -0.72 (+/-0.03) kcal x mol(-1)
per nucleotide. The mean cooperativity coefficient (omega) was 24.5 (+/- 5.6),
and the corresponding free energy of interaction between the neighbouring
oligonucleotides in the third strand was DeltaG(0(omega)) = -1.74 (+/-0.13) kcal
x mol(-1).
PMID- 17029900
TI - A simple theory of motor protein kinetics and energetics.
AB - A simple stochastic theory for kinetics and energetics of the movement of single
motor proteins is presented. The model combines the biochemical cycle of
nucleotide hydrolysis with the motor protein translocation. Based on the theory
of Markov processes, the model provides the force-velocity relationship, the
isometric force, and the stochastic stepping of the motor protein along its one
dimensional track. The theoretical model provides a conceptual framework for
realistic studies of motor proteins. Relationship between the present theory and
other existing models is discussed.
PMID- 17029901
TI - Repair effect of phenylpropanoid glycosides on thymine radical anion induced by
pulse radiolysis.
AB - Repair effects on thymine radical anion by six phenylpropanoid glycosides (PPGs),
isolated from Pedicularis species, were studied using pulse radiolysis method.
The thymine radical anion was produced by the reaction of hydrated electron with
thymine. PPGs were added into the thymine solution saturated with N(2). Kinetic
analysis showed that transient absorption spectrum of thymine radical anion
formed at first, and then after several microseconds of pulse radiolysis changed
to that of PPG radical anion. The evidence indicated that thymine radical anion
was repaired through one-electron transfer between the radical anion and PPG.
Electrophilic phenyl-substituted unsaturated carboxylic group containing in PPGs'
structure was able to capture electron from thymine radical anion before it
undergo reversible protonation. The reaction rate constants of electron transfer
from thymine radical anion to PPGs were within 1.16-2.29 x 10(9) dm(3) mol(-1) s(
1).
PMID- 17029902
TI - Production of soybean isoflavone genistein in non-legume plants via genetically
modified secondary metabolism pathway.
AB - Genetic modification of secondary metabolic pathways to produce desirable natural
products is an attractive approach in plant biotechnology. In our study, we
attempted to produce a typical soybean isoflavone genistein, a well-known health
promoting metabolite, in non-legume plants via genetic engineering. Both
overexpression and antisense suppression strategies were used to manipulate the
expression of several genes encoding key enzymes in the flavonoids/isoflavonoids
pathway in transgenic tobacco, lettuce, and petunia. Introducing soybean
isoflavone synthase (IFS) into these plants, which naturally do not produce
isoflavonoids due to a lack of this leguminous enzyme, resulted in genistein
biosynthesis in tobacco petals, petunia leaves and petals, and lettuce leaves. In
tobacco, when flavanone 3-hydroxylase (F3H) expression was suppressed by its
antisense gene while soybean IFS was overexpressed at the same time, genistein
yield increased prominently. In addition, overexpression of phenylalanine ammonia
lyase (PAL) also led to an enhanced genistein production in tobacco petals and
lettuce leaves in the presence of IFS than in the plants that overexpressed only
IFS.
PMID- 17029903
TI - Methodology for adding glycemic index and glycemic load values to 24-hour dietary
recall database.
AB - OBJECTIVES: We describe a method of adding the glycemic index (GI) and glycemic
load (GL) values to the nutrient database of the 24-hour dietary recall interview
(24HR), a widely used dietary assessment. We also calculated daily GI and GL
values from the 24HR. METHODS: Subjects were 641 healthy adults from central
Massachusetts who completed 9067 24HRs. The 24HR-derived food data were matched
to the International Table of Glycemic Index and Glycemic Load Values. The GI
values for specific foods not in the table were estimated against similar foods
according to physical and chemical factors that determine GI. Mixed foods were
disaggregated into individual ingredients. RESULTS: Of 1261 carbohydrate
containing foods in the database, GI values of 602 foods were obtained from a
direct match (47.7%), accounting for 22.36% of dietary carbohydrate. GI values
from 656 foods (52.1%) were estimated, contributing to 77.64% of dietary
carbohydrate. The GI values from three unknown foods (0.2%) could not be
assigned. The average daily GI was 84 (SD 5.1, white bread as referent) and the
average GL was 196 (SD 63). CONCLUSION: Using this methodology for adding GI and
GL values to nutrient databases, it is possible to assess associations between GI
and/or GL and body weight and chronic disease outcomes (diabetes, cancer, heart
disease). This method can be used in clinical and survey research settings where
24HRs are a practical means for assessing diet. The implications for using this
methodology compel a broader evaluation of diet with disease outcomes.
PMID- 17029904
TI - Gender difference in the effect of intrauterine malnutrition on the central
anorexigenic action of insulin in adult rats.
AB - OBJECTIVE: We evaluated whether insulin hypophagia and hypothalamic signaling are
affected in adult rats exposed to intrauterine undernutrition. METHODS: Pregnant
rats ate ad libitum throughout pregnancy and lactation (control, C) or 50% of
control intake in the first 2 wk of pregnancy (restricted, R). Four-month-old C
and R progeny received insulin or vehicle intracerebroventricular injections for
evaluation of 24-h food intake, hypothalamic insulin receptor (IR), and IR
substrate-1 (IRS-1) protein content and tyrosine phosphorylation, pp185
phosphorylation, and IRS-1 association with phosphatidylinositol 3-kinase (PI3
K). RESULTS: With respect to males, R males had normal body composition and
insulin-induced hypophagia. IR protein levels were lower but IR phosphorylation
was higher in R than in C males. IRS-1 levels and phosphorylation were similar
between C and R males, insulin stimulated an IRS-1/PI3-K association in C but not
in R males, and pp185 phosphorylation was higher in R than in C males. For
females, body fat and serum leptin were elevated in R females. Insulin inhibited
food intake in C but not in R females. Insulin-induced IR phosphorylation and
protein levels of IR and IRS-1 were higher in R than in C females. However, IRS-1
and pp185 phosphorylation and IRS-1/PI3-K association were significantly
stimulated by insulin in C but not in R females. CONCLUSIONS: Female adult rats
exposed to intrauterine undernutrition had increased adiposity, marked impairment
of hypothalamic insulin signaling, and loss of insulin-induced hypophagia. These
disturbances were less severe or even absent in male progeny. The findings show
that female progeny are more susceptible than their male siblings to the effects
of maternal malnutrition.
PMID- 17029905
TI - Nucleic acid structure and recognition.
AB - We review the global structures adopted by branched nucleic acids, including
three- and four-way helical junctions in DNA and RNA. We find that some general
folding principles emerge. First, all the structures exhibit a tendency to
undergo pairwise coaxial helical stacking when permitted by the local
stereochemistry of strand exchange. Second, metal ions generally play an
important role in facilitating folding of branched nucleic acids. These
principles can be applied to functionally important branched nucleic acids, such
as the Holliday DNA junction of genetic recombination, and the hammerhead
ribozyme in RNA.
PMID- 17029906
TI - Electron transfer and electronic energy relaxation under high hydrostatic
pressure.
AB - The following question has been addressed in the present work. How external high
(up to 8 kbar) hydrostatic pressure acts on photoinduced intramolecular electron
transfer and on exciton relaxation processes? Unlike phenomena, as they are, have
been studied in different systems: electron transfer in an artificial Zn
porphyrin-pyromellitimide (ZnP-PM) supramolecular electron donor-acceptor complex
dissolved in toluene measured at room temperature; exciton relaxation in a
natural photosynthetic antenna protein called FMO protein measured at low
temperatures, between 4 and 100 K. Spectrally selective picosecond time-resolved
emission technique has been used to detect pressure-induced changes in the
systems. The following conclusions have been drawn from the electron transfer
study: (i) External pressure may serve as a potential and sensitive tool not only
to study, but also to control and tune elementary chemical reactions in solvents;
(ii) Depending on the system parameters, pressure can both accelerate and inhibit
electron transfer reactions; (iii) If competing pathways of the reaction are
available, pressure can probably change the branching ratio between the pathways;
(iv) The classical nonadiabatic electron transfer theory describes well the
phenomena in the ZnP-PM complex, assuming that the driving force or/and
reorganisation energy depend linearly on pressure; (v) A decrease in the ZnP-PM
donor-acceptor distance under pressure exerts a minor effect on the electron
transfer rate. The effect of pressure on the FMO protein exciton relaxation
dynamics at low temperatures has been found marginal. This may probably be
explained by a unique structure of the protein [D.E. Trondrud, M.F. Schmid, B.W.
Matthews, J. Mol. Biol. 188 (1986) p. 443; Y.-F. Li, W. Zhou, E. Blankenship,
J.P. Allen, J. Mol. Biol., submitted]. A barrel made of low compressibility beta
sheets may, like a diving bell, effectively screen internal bacteriochlorophyll a
molecules from external influence of high pressure. The origin of the observed
slow pico = and subnanosecond dynamics of the excitons at the exciton band bottom
remains open. The phenomenon may be due to weak coupling of phonons to the
exciton states or/and to low density of the relevant low-frequency (
approximately 50 cm(-1)) phonons. Exciton solvation in the surrounding protein
and water-glycerol matrix may also contribute to this effect. Drastic changes of
spectral, kinetic and dynamic properties have been observed due to protein
denaturation, if the protein was compressed at room temperature and then cooled
down, as compared to the samples, first cooled and then pressurised.
PMID- 17029907
TI - Modern science and the explosion of new knowledge.
AB - The technological evolution of mankind accelerated enormously after the
institutionalization of science in the 19th century. In parallel with the vast
number of beneficial effects derived from the scientific revolution, the
explosion of new knowledge and its centralization in only a few countries has
generated a number of complex situations that present major challenges for the
modern science. These include the asymmetrical distribution in the planet of
young people and science, the super-specialization derived from the information
overload and the difficulties in teaching the vast amount of new knowledge
generated each year by science.
PMID- 17029908
TI - Biophysical properties of epithelial water channels.
AB - The biophysical models describing the structure of water pores or channels have
evolved, during the last forty years, from a pure 'black box' approach to a
molecular based proposal. The initial 'sieving pore' in which water and other
molecules were moving together was replaced by a more restrictive model, where
water is moving alone in a 'single file' mode. Aquaporins discovery and cloning
[G.M. Preston, T.P. Carroll, W.B. Guggino, P. Agre, Science 256 (1992) 365]
leaded to the 'hour-glass model' and other alternative proposals, combining
information coming from molecular biology experiments and two dimensional
crystallography. Concerning water transfers in epithelial barriers the problem is
quite complex, because there are at least two alternative pathways: paracellular
and transcellular and three different driving forces: hydrostatic pressure,
osmotic pressure or 'transport coupled' movements. In the case of ADH-sensitive
epithelia it is more or less accepted that regulated water channels (AQP2), that
can be inserted in the apical membrane, coexist with basolateral resident water
channels (AQP3). The mechanism underlying the so-called 'transport associated
water transfer' is still controversial. From the classical standing gradient
model to the ion-water co-transport, different hypothesis are under
consideration. Coming back to hormonal regulations, other than the well-known
regulation by neuro-hypophysis peptides, a steroid second messenger,
progesterone, has been recently proposed [P. Ford, G. Amodeo, C. Capurro, C.
Ibarra, R. Dorr, P. Ripoche, M. Parisi, Am. J. Physiol. 270 (1996) F880].
PMID- 17029910
TI - A re-analysis of the relationship among coping, symptom severity and quality of
life in schizophrenia.
PMID- 17029909
TI - Impaired verbal source monitoring in schizophrenia: an intermediate trait
vulnerability marker?
AB - Patients with schizophrenia, particularly those with positive symptoms show
impaired verbal source monitoring. Specific cognitive deficits have been observed
during both active and remission phases of the illness as well as in groups of
unaffected first degree relatives of patients with schizophrenia. This type of
schizophrenia vulnerability marker may precede the onset of frank psychotic
symptoms and contribute to their developments. The aim of this study was first to
determine if unaffected siblings were impaired in discriminate internal vs.
external generated events when compared to their remitted schizophrenics
relatives and healthy subjects. Performances of healthy subjects were then
compared with results from previous studies with acute hallucinating patients,
acute non-hallucinating patients and patients with resistant auditory verbal
hallucinations. Compared with healthy subjects, unaffected siblings are impaired
(effect size, ES=0.7), remitted or acute non-hallucinating patients are more
impaired than siblings (ES=1.4); patients with verbal auditory hallucinations
(acute or resistant) are even more impaired than non-hallucinating patients
(ES=2.1). Our results suggest that a source monitoring deficit could be
considered as an intermediate vulnerability marker of schizophrenia.
PMID- 17029911
TI - STR loci D10S2325, D16S539 and D19S253: Northern Thai population data.
AB - The STR loci D10S2325, D16S539 and D19S253 were analyzed in 203 unrelated
Northern Thai. A power of discrimination of 0.954, 0.923 and 0.921 and a power of
exclusion of 0.690, 0.542 and 0.632, respectively were found. The combined power
of discrimination and exclusion reached 0.99972 and 0.9478, respectively. No
deviation from the Hardy-Weinberg equilibrium was observed for the three loci.
PMID- 17029912
TI - Amphetamine pretreatment accelerates the subsequent escalation of cocaine self
administration behavior.
AB - It has been proposed that some neuroadaptations that underlie behavioral
sensitization may play a role in the development and persistence of addiction.
However, whether or not sensitization facilitates the development of symptoms
specific to addiction, such as the escalation of drug intake, is not known. We
examined, therefore, the effect of pretreatment with a sensitizing regimen of
amphetamine on the escalation of subsequent drug intake in rats given the
opportunity to self-administer cocaine. Amphetamine pretreatment produced
psychomotor sensitization and also accelerated the subsequent escalation of
cocaine intake. This suggests that the neural circuits that are altered as a
consequence of repeated amphetamine treatment, and the induction of
sensitization, may overlap with those responsible for the development of some
addiction-like behaviors.
PMID- 17029913
TI - Association of the serotonin transporter promotor polymorphism with suicide
attempters with a high medical damage.
AB - Serotonergic neurotransmission has been implicated in suicidal behavior,
including inconsistent results concerning the serotonin transporter promoter
polymorphism (5-HTTLPR). Here, we analyzed the 5-HTTLPR in suicide attempters
(n=85). Comparing the presence of SS with SL+LL genotypes showed a significantly
higher prevalence of the SS genotype in suicide attempters with high medical
damage scores (chi2=9.054, df=1, p=0.0026). The results suggest that the S-allele
may predispose for suicidal behavior characterized by high determination.
PMID- 17029914
TI - Molecular dynamics simulation of a dye molecule in the interior of a bilayer: 1,6
diphenyl-1,3,5-hexatriene in dipalmitoylphosphatidylcholine.
AB - A molecular dynamics simulation was carried out for a
dipalmitoylphosphatidylcholine (DPPC) membrane in its liquid crystalline state
containing different concentrations of the dye molecule 1,6-diphenyl-1,3,5
hexatriene (DPH). From a numerical analysis of the trajectories, we obtained
information concerning structural changes of the membrane due to the presence of
the probe and some hydrodynamic information concerning the probe itself. The
hydrodynamic properties regarding dye molecules that have been reported in this
article are: rotational and translational diffusion coefficient and relaxation
times. From this analysis, we estimated a range of values of 0.6-0.9 cP for the
micro-viscosity in the mid-membrane. These simulations also afforded us some
information regarding structural changes in the membrane as a consequence of the
presence of the fluorescent dyes at different concentrations. Thus, the disorder
inside the membrane, the surface area per lipid and thickness of the membrane
were also investigated.
PMID- 17029915
TI - Effects of cholesterol on membrane surfaces as studied by high-pressure
fluorescence spectroscopy.
AB - We have studied the effects of cholesterol on membrane surfaces using
fluorescence spectroscopy at high pressure. At atmospheric pressure, the
dissociation state of a pH-sensitive fluorophore (6-decanylnaphthol or DECNA)
incorporated into several types of membranes showed an apparent increase in
dissociation with cholesterol content coming somewhat closer to its dissociation
state in solution. Previous studies have shown that when DECNA is free in
solution, pressure induces proton dissociation due to the volume decrease that
occurs when water electrostricts around the ions. But in phosphatidylcholine (PC)
bilayers, proton dissociation is inhibited, either due to the inability of the
surface to expand and allow for increased hydration, or other changes in lipid
structure. The pressure behavior of DECNA in dioleoyl-PC, dioleoylphosphatidic
acid and dioleylphosphatidylglycerol bilayers shows that incorporation of 5-10%
cholesterol causes DECNA to behave like it is in a more unrestricted environment.
This trend is reversed at higher cholesterol concentrations. These data, together
with compressibility measurements, support the model of Sankaram and Thompson [M.
Sankaram, T.E. Thompson, Biochemistry 29 (1990) 10676.] whereby in the disordered
phase, cholesterol can span the two leaflets causing an increase in the area
between the head groups; whereas in the ordered phase, no expansion occurs. Thus,
the effect of cholesterol on membrane surfaces depends on its phase diagram.
PMID- 17029916
TI - Heat capacity and thermodynamic characteristics of denaturation and glass
transition of hydrated and anhydrous proteins.
AB - Calorimetric measurements of absolute heat capacity have been performed for
hydrated (11)S-globulin (0 < C(H(2)O) < 25%) and for lysozyme in a concentrated
solution, both in the native and denatured states. The denaturation process is
observed in hydrated and completely anhydrous proteins; it is accompanied by the
appearance of heat capacity increment (Delta(N)(D)C(p)), as is the case for
protein solutions. It has been shown that, depending on the temperature and water
content, the hydrated denatured proteins can be in a highly elastic or glassy
states. Glass transition is also observed in hydrated native proteins. It is
found that the denaturation increment Delta(N)(D)C(p) in native protein, like the
increment DeltaC(p) in denatured protein in glass transition at low water
contents, is due to additional degrees of freedom of thermal motion in the
protein globule. In contrast to the conventional notion, comparison of absolute
C(p) values for hydrated denatured proteins with the C(p) values for denatured
proteins in solution has indicated a dominant contribution of the globule thermal
motion to the denaturation increment of protein heat capacity in solutions. The
concentration dependence of denaturing heat absorption (temperature at its
maximum, T(D), and thermal effect, DeltaQ(D)) and that of glass transition
temperature, T(g), for (11)S-globulin have been studied in a wide range of water
contents. General polymeric and specific protein features of these dependencies
are discussed.
PMID- 17029917
TI - Wrongful convictions, lessons learned: the Canadian experience.
AB - Following the wrongful conviction of a man for the sexual assault and murder of a
child, the Province of Ontario commissioned a public inquiry to prevent future
miscarriages of justice. The implementation of several recommendations regarding
forensic laboratory procedure and the presentation of expert evidence has proven
to be beneficial to the Canadian criminal justice system.
PMID- 17029918
TI - Drugged driving in Hungary 2000-2004.
AB - The authors analyzed the biological samples available in criminal cases that were
started because of illicit and prescribed drug-impaired driving between 2000 and
2004. The result of the on-the-spot clinical test is not informative and cannot
be evaluated as it is mainly affected by the simultaneous presence of alcohol.
Licit or illicit drugs in the urine could be detected in 378 people out of 623
people (60.7%), whereas in 59 cases (9.5%) there was some substance present in
the blood. The occurrence multiple drugs was high (36.8%). The joint use of
alcohol and drugs has increased in the past few years.
PMID- 17029919
TI - The pathology of the heart conduction system in congenital heart block.
AB - The incidence of congenital complete heart block is estimated in 1 of 2500-20,000
births. Many cases are isolated (found in an otherwise normal heart) and the
pathology of the heart conduction system is variable. We report a 51-year-old man
with the diagnosis of complete heart block, with a permanent pacemaker. No family
history of rhythm disturbances was available. The patient presented and
endocarditis after replacement of the pacemaker battery. The prognosis was poor
and the patient died three months later. Autopsy examination showed signs of
shock, of septic origin. The heart was hypertrophic (450g) and the left ventricle
thickened. Histopathological examination of the heart conduction system showed
that the sinus and atrioventricular nodes were normal, but the His bundle was
interrupted and replaced by fibrous tissue. No inflammatory signs were present.
Loss of conducting fibres and their replacement by fibrous tissue is the most
common pathological process in complete heart block. In this case His bundle was
mostly affected, different to Lev's disease where the process is more distal
(branching atrioventricular bundle) and to Lenegre's disease, which shows a
diffuse damage in the conducting system.
PMID- 17029920
TI - Spontaneous oesophageal perforation.
AB - An autopsy was performed on a young adult, who apparently died during his sleep.
Mediastinitis was established and empyema was also found in left pleural cavity.
The oesophagus examination showed a tear in left side. The lesion occurred in the
distal oesophagus and showed the leak communicating freely with the left pleural
space. Oesophageal perforation was the source of empyema, resulted from
barotrauma to the lower oesophagus during the effort of vomiting. Death caused by
septic shock. Boerhaave syndrome is a serious and rapidly fatal spontaneous
oesophagus rupture. Forceful ejection of gastric contents in an unrelaxed
oesophagus against a closed glottis is the mechanism described. The tear thus
produced is vertical. The case report discusses the historical, statistical,
pathophysiological, diagnostic and therapeutic aspects of Boerhaave syndrome. The
syndrome is a cause of sudden death, which be known by forensic pathologists.
PMID- 17029921
TI - Forensic and criminologic aspects of murder in North-West (Epirus) Greece.
AB - Little information is presenting in Greek literature regarding forensic and
criminological aspects of homicide in North-West Greece. Autopsy reports and the
prosecution authorities' files were respectively analyzed with regard to
individual characteristics of perpetrators and victims, circumstances, and mode
of commitment in order to comprehensively characterize relevant forensic and
criminologic aspects. In the 8-year period from January 1998 to May 2005, 26
homicide cases were autopsied in the Department of Forensic Medicine and
Toxicology, University of Ioannina, Greece. Twenty-nine homicide victims (18
males, 11 females; mean age 47 years) and 26 offenders were involved--20 single,
4 multiple-offenders and 2 were not known (24 males, 2 females; mean age 35
years). The most common method used for homicide was gunshot trauma (41.4%). Head
injuries and multiple trauma were the most common cause of fatal injuries. Most
homicides took place outside in a deserted area or close to agricultural side
(n=12). Fifty percent (n=13) of all cases the offender and the victim were known
to each other (acquaintances). Twenty-three cases were categorized as "single"
homicides and 3 as "multiple" and the victims were classified; 20 as murder
physical injury with fatal outcome, 2 homicide-suicide, 1 infanticide, 4
matricide, and 2 as patricide.
PMID- 17029922
TI - Molecular biology of distal muscular dystrophies--sarcomeric proteins on top.
AB - During the last 10 years several muscular dystrophies within the group of distal
myopathies have been clarified as to the molecular genetic cause of the disease.
Currently, the next steps are carried out to identify the molecular pathogenesis
downstream of the gene defects. Some early ideas on what is going on in the
muscle cells based on the defect proteins are emerging. However, in no single
distal muscular dystrophy these efforts have yet reached the point where direct
trials for therapy would have been launched, and in many distal dystrophies the
causative gene is still lacking. When comparing the gene defects in the distal
dystrophies with the more common proximal muscular dystrophies such as
dystrophinopathies or limb-girdle muscular dystrophies, there is a striking
difference: the genes for distal dystrophies encode sarcomere proteins whereas
the genes for proximal dystrophies more often encode sarcolemmal proteins.
PMID- 17029923
TI - Comparative views of the public, sex workers, businesses and residents on
establishing managed zones for prostitution: analysis of a consultation in
Liverpool.
AB - Drug addiction, violence and anti-social behaviour are characteristics of street
prostitution. An alternative approach to zero tolerance is establishing a managed
zone where sex workers operate according to regulations and can access health
services. Using a consultation with sex workers (n=50), businesses (n=51),
residents (n=179) and the public (n=789) we examined where a zone might be
established in a UK city (Liverpool) and characteristics of the zone required by
these stakeholders. All groups believed a zone would improve sex workers' safety
and reduce prostitution elsewhere. Sex workers (96%) agreed to work in a zone.
Location criteria from all groups were used to identify two potential business
areas to host a zone but businesses in or near these areas rejected plans through
fear for staff safety and reduced business. We discuss the consultation process,
difficulties in locating services for marginalised groups in cities and the
implications for health and judicial policy relating to prostitution.
PMID- 17029924
TI - Transitions and new dynamical states induced by noise in a multiply regulated
biochemical system.
AB - Noise-induced transitions between coexisting states, and the emergence of a new
oscillatory state, are examined in a model for a multiply regulated biochemical
system. For the undisturbed system, three oscillatory states, I, II, and III,
coexist. It is found that noise above a critical amplitude can cause a transition
between states III and II and between states III or II and state I, whereas a
transition from state I to either states II or III is never observed. This
indicates that the relative stability under noise perturbations is greatest for
state I, and progressively less for states II and III. In addition to this
transition behaviour, a purely noise-induced state is found. Under noise
perturbations, the average concentration of metabolites may depend on both the
time duration and amplitude of the superimposed noise. The implications of these
results for understanding the in vivo behaviour of complex biochemical systems
are discussed.
PMID- 17029925
TI - Analysis of differential scanning calorimetry data for proteins. Criteria of
validity of one-step mechanism of irreversible protein denaturation.
AB - We consider in this work the analysis of the excess heat capacity C(p)(ex) versus
temperature profiles in terms of a model of thermal protein denaturation
involving one irreversible step. It is shown that the dependences of ln C(p)(ex)
on 1 T (T is the absolute temperature) obtained at various temperature scanning
rates have the same form. Several new methods for estimation of parameters of the
Arrhenius equation are explored. These new methods are based on the fitting of
theoretical equations to the experimental heat capacity data, as well as on the
analysis of the dependence d(ln C (p)(ex)) d ( 1 T ) on 1 T . We have applied the
proposed methods to calorimetric data corresponding to the irreversible thermal
denaturation of Torpedo californica acetylcholinesterase, cellulase from
Streptomyces halstedii JM8, and lentil lectin. Criteria of validity for the one
step irreversible denaturation model are discussed.
PMID- 17029926
TI - Thermodynamic analysis of amines-lasalocid complex formation.
AB - The ionophore lasalocid A selectively transports amines across lipid membranes.
Free energy differences of amine-lasalocid complex formation reactions and the
activation barriers of the complex transport were calculated by the finite
difference thermodynamic integration method. Four catecholamines were treated:
serotonin > dopamine > noradrenaline > adrenaline. The concept of transfer
selectivity was introduced, combining binding and activation barrier
selectivities. The transfer selectivities correlate well with the relative
selectivities of the amines under study.
PMID- 17029927
TI - Long-term molecular dynamics simulation of copper plastocyanin in water.
AB - A long molecular dynamics simulation (1.1 ns) of fully hydrated plastocyanin has
been performed and analysed to relate protein dynamics to structural elements and
functional properties. The solvated structure is described in detail by the
analysis of H-bond network. During all the simulation, the crystal H-bond network
is maintained in the beta-sheet regions, while several H-bonds are broken or
formed on the external surface of the protein. To evaluate whether such changes
could be due to conformational rearrangements or to solvent competition, we have
examined the average number of H-bonds between protein atoms and water molecules,
and the root mean square deviations from crystal structure as a function of
protein residues. Protein mobility and flexibility have been examined by
positional and dihedral angle rms fluctuations. Finally, cross-correlation maps
have revealed the existence of correlated motions among residues connected by
hydrogen bonds.
PMID- 17029928
TI - Complex dynamics of mass-closed coupled autocatalytic systems in response to
minute asymmetric perturbations.
AB - The role of kinetic coupling in catering to a remote-control mechanism for the
onset and regulation of self-organization phenomena in a multicompartmental
biochemical system has been examined. Using two cyclic autocatalytic reaction
networks operating in two chambers separated by a membrane and coupled through a
common cofactor, it has been demonstrated that (i) in response to asymmetric
perturbations, the coupled reaction networks exhibit a variety of temporal self
organization phenomena such as bistability, multiple periodicity, hard excitation
and coexistence of aperiodic oscillation with limit cycle even in mass-closed
conditions; (ii) without disturbing a network directly, its dynamic behaviour can
be regulated by perturbing some other network kinetically coupled to it and (iii)
the dynamics of two coupled networks can be made to flip-flop between oscillatory
and steady-states simply by modulating the time of application of external
perturbations. The extreme sensitivity of this model to minute asymmetric
fluctuations in the environment can predict how the impact of local changes in
physico-chemical conditions can be transmitted from one compartment to another
through coupled biochemical pathways in a living cell.
PMID- 17029929
TI - A correction to the calculation of the Gibbs free energy of adsorption for
biomolecules in ion-exchange systems.
AB - We wish to propose a correction to the methodology introduced by Gerstner et al.
[J.A. Gerstner, J.A. Bell, S.M. Cramer, Biophys. Chem. 52 (1994) 97-106] for the
calculation of Gibbs free energies of adsorption of biomolecules to ion-exchange
systems. Our approach is based on the requirement that the mobile phase and
stationary phase concentrations be expressed in exactly the same units and the
equilibrium constant be strictly dimensionless. The Gibbs free energies of ion
exchange calculated based on this correction appear to be more negative than
those originally calculated by Gertner et al.
PMID- 17029930
TI - Secondary structure of an isolated P-region from the voltage-gated sodium
channel: a molecular modelling/dynamics study.
AB - Conformational studies of synthetic peptides corresponding to the pore-forming
regions of voltage-gated sodium channels show a high tendency for beta-sheet
conformation when interacting with lipid vesicles, as revealed by circular
dichroism and infrared spectroscopy. These observations have guided our choice of
possible molecular models for the P-region peptide of domain II of voltage-gated
sodium channels: three alternative beta-hairpins, with differing turn
assignments, or an alpha-helical hairpin. After generation of models by distance
geometry-based methods, molecular dynamics (MD) simulations were run. in the
absence of explicit solvent molecules but employing three different dielectric
constants, to explore possible conformational preferences. The simulations in the
different dielectric environments suggest that a 4-residue turn with the sequence
LCGE yields more stable beta-hairpins. The MD results suggest that the SS1 part
of the peptide may be more stable as an alpha-helix, whereas the SS2 part tends
to adopt a beta-conformation.
PMID- 17029931
TI - Photosynthesis as a power supply for (bio-)hydrogen production.
AB - Although hydrogen is considered to be one of the most promising future energy
sources and the technical aspects involved in using it have advanced
considerably, the future supply of hydrogen from renewable sources is still
unsolved. This review focuses on the production of hydrogen from water using
biological catalysts that have been optimized by nature: the process of water
splitting photosynthesis on the one hand and hydrogen production via the catalyst
hydrogenase on the other. Using water as a source of electrons and sunlight as a
source of energy, both engineered natural systems and biomimetic (bio-inspired)
model systems can be designed as first steps towards water-splitting-based
hydrogen production (biophotolytic hydrogen production).
PMID- 17029932
TI - The ABC's of comparative genomics in the Brassicaceae: building blocks of
crucifer genomes.
AB - In this review we summarize recent advances in our understanding of
phylogenetics, polyploidization and comparative genomics in the family
Brassicaceae. These findings pave the way for a unified comparative genomic
framework. We integrate several of these findings into a simple system of 24
conserved chromosomal blocks (labeled A-X). The naming, order, orientation and
color-coding of these blocks are based on their positions in a proposed ancestral
karyotype (n=8), rather than by their position in the reduced genome of
Arabidopsis thaliana (n=5). We show how these crucifer building blocks can be
rearranged to model the genome structures of A. thaliana, Arabidopsis lyrata,
Capsella rubella and Brassica rapa. A framework for comparison between species is
timely because several crucifer genome-sequencing projects are underway.
PMID- 17029933
TI - [Fulminant myocarditis presenting like acute myocardial infarction in a 6-year
old girl].
AB - Acute myocarditis is a rare inflammatory cardiac disease in children with
potentially fatal issue. Clinical findings are very variable from nausea and
vomiting to acute cardiovascular collapse. The cardiac function can be reversible
with circulatory support. We report the case of a 6-year-old girl with ECG
changes like myocardial infarction and diagnosis of fulminant myocarditis. She
developped rapidly a cardiogenic shock and died before treatment with mechanical
circulatory support.
PMID- 17029934
TI - [Listeria monocytogenes meningitis in an immunocompetent child].
PMID- 17029935
TI - [Babywalker use (baby-trot, youpala): an unsafe practice].
AB - AIM: Epidemiological analysis of accidents related to babywalker use admitted to
a pediatric emergency department. METHODS: Retrospective, descriptive study of
injuries related to babywalkers admitted to the pediatric emergency department
between January 1st, 2003 and December 31st, 2005. RESULTS: One hundred and
seventy-eight children were admitted due to an accident related to babywalker
use. The sex ratio was 1.7 with a male prevalence. Mean age was 11+/-4 months.
Seventy-eight percent of babywalker-related injuries were attributable to fall
down a flight of stairs. The mean number of steps that a child fell down was 7
(range 1-20 steps). The repartition of accidents was bimodal: during the year, 1
peak in May and 1 in October; during the week: 54% of the cases occurred on
Thursday or on the weekend; during the day (1 peak between 10 a.m. and 1 p.m. and
1 peak between 4 p.m. and 7 p.m.). Non-severe head traumas represented the most
frequent injury (72%). Twenty-one children were hospitalised for concussion
(N=15), cranial fractures (N=3), forearm fracture (N=1), dental subluxation (N=1)
and extradural hematoma (N=1). A social problem (families with unsafe domestic
practices) was identified in 26 children (15%), 16 of these situations were
recognized due to the retrospective character of the study and the analysis of
hospital admissions after the first accident. CONCLUSION: Stairway related falls
associated with babywalker use and fall down in the stairs are very frequent in
children less than 1 year-old. This resulted in babywalkers being prohibited in
Canada since 2004. In several countries, advocates are working to ban
babywalkers. Active or passive prevention methods have shown their limits. This
unsafe and dangerous practice should be banned in France.
PMID- 17029936
TI - Detrimental effect of eicosapentaenoic acid supplementation on bone following
ovariectomy in rats.
AB - Although several studies have reported a positive effect of n-3 essential fatty
acids (EFAs) on bone density post-ovariectomy, the role of specific EFAs has yet
to be fully elucidated. In this study, ovariectomised (OVX) rats were
supplemented with 0.1 g (LOW) or 1.0 g (HIGH) of eicosapentaenoic acid (EPA)/kg
body weight for 9 weeks. Bone mineral density (BMD), 25-hydroxyvitamin D(3) and
plasma fatty acid profile were compared to those of OVX and sham animals fed a
non-supplemented diet. BMD decreased significantly in all OVX (P<0.001) but not
sham rats. There was no difference in BMD between the LOW group and OVX controls.
BMD was significantly lower in the HIGH group compared to OVX and sham controls.
25-hydroxyvitamin D(3) levels were significantly higher in both the LOW and HIGH
groups compared to OVX controls (P=0.0006 and 0.02, respectively). In conclusion,
high-dose EPA supplementation exacerbated the effects of ovariectomy on BMD.
PMID- 17029937
TI - Allergy and hypersensitivity: mechanisms of allergic disease.
PMID- 17029939
TI - Social determinants of access to reference care centres for patients with
colorectal cancer--a multilevel analysis.
AB - BACKGROUND: Although social disparities in survival for patients with cancer are
documented in an increasing number of papers, knowledge on the underlying
mechanisms concerning screening, diagnosis, treatment or follow-up, is relatively
poor. Our study was aimed at investigating the social determinants of access to
reference cancer care centres for surgery for colorectal cancer in France.
METHODS: Retrospective analysis was conducted on population-based data from a
specialised cancer registry (County of Calvados, France). The population
consisted of 5156 patients with surgical treatment for colorectal cancer recorded
between January 1st 1981 and December 31st 2000. RESULTS: The probability of
being cared for in a reference care centre was 1.3-fold lower for people living
in a deprived district (mean income < 15000 euros) and 3-fold lower for people
living in a district where more than 7% of houses were devoid of bath and shower
in comparison with districts where this rate was under 2%. After adjustment for
distance from reference care centre, the probability of being cared for in a
reference care centre was still over one third lower for people living in a
district with more than 7% of houses devoid of bath and shower. Social
disparities in management of patients with colorectal cancer have increased in
the last decade. The reduction of access to reference care with distance was
stronger in elderly patients. CONCLUSIONS: There is a social and geographical
determination of type of treatment centre for care management of colorectal
cancer in France. Special attention needs to be paid to the high quality of care
management in non-specialised care centres in order to avoid an increased social
gradient in cancer mortality in France.
PMID- 17029940
TI - Vibrational spectra of metals treated with allyltrimethoxysilane sol-gel and self
assembled monolayer of allytrichlorosilane.
AB - A sol-gel has been prepared by using allyltrimethoxysilane (ATMS) as precursor,
ethanol as homogenizer as well as solvent, and hydrochloric acid as catalyst. The
sol-gel was employed for the coating treatment of aluminum. Self-assembled
monolayer (SAM) with allyltrichlorosilane (ATCS) is another method used for the
metal surface treatment in the present work. The treated metal surfaces were
characterized with reflection adsorption infrared spectra (RAIR). Detailed
interpretation and vibrational assignment have been given to the collected IR
spectra of the sol-gel, xerogel and surface films of ATMS and the SAM of ATCS on
aluminum as well as pure silanes. A series of investigation of the UV exposure
and temperature effects has been carried out. Results from the investigation
indicate that the UV radiation exposure or the high temperature thermal treatment
will induce a chemical process on the organosilica coated surfaces.
PMID- 17029941
TI - Fluorescent quenching method for determination of trace hydrogen peroxide in rain
water.
AB - A simple and sensitive fluorescent quenching method for the determination of
trace hydrogen peroxide (H(2)O(2)) has been proposed to determine hydrogen
peroxide in rain water sample. The method is based on the reaction of H(2)O(2)
with 3,3'-diethyloxadicarbocyanine iodide (DI) to form a compound which has no
fluorescence in acetate buffer solution (pH 3.09). The maximum emission
wavelength of the system is located at 604 nm with excitation at 570 nm. Under
the optimal conditions, the calibration graph was obtained between the quenched
fluorescence intensity and hydrogen peroxide concentration in the range of 5.0 x
10(-7) to 9.0 x 10(-4) mol L(-1). The proposed method was applied to determine
H(2)O(2) in rain water samples, and the result was satisfactory. The mechanism
involved in the reaction was also studied.
PMID- 17029942
TI - Vibrational spectroscopic studies of an organic non-linear optical crystal 8
hydroxyquinolinium picrate.
AB - 8-hydroxyquinolinium picrate (8-HQP) was synthesized by the addition of equimolar
quantities of 8-hydroxyquinoline (8-HQ) and picric acid (PA). Single crystals
were grown from N,N dimethyl formamide (DMF) by restricted evaporation method at
room temperature. The solubility of 8-HQP was determined in different solvents at
various temperatures. The structural characterization of the grown crystals was
carried out by X-ray diffraction. Vibrational modes were classified on the basis
of group theoretical analysis and the spectral bands were compared with those of
parent compounds in order to propose a tentative assignment by recording FT-IR,
FT-Raman and polarized Raman spectra in different crystal orientations. The
crystal possess lower cut-off at 230 nm and good transparency as confirmed by
optical transmittance studies.
PMID- 17029943
TI - Interatomic potential parameters of CdHe van der Waals complex derived from
excitation spectrum of the C1 1(51P1)<--X10+(51S0) vibrational transition.
AB - The first time observed excitation spectrum of the C(1)1(5(1)P(1))<-
X(1)0+(5(1)S(0)) transition in CdHe van der Waals molecules is reported.
Vibrational spectrum in the UV region (2286.0-2296 A) was excited in a continuous
molecular-jet-expansion beam of CdHe seeded in helium using an in-house-built
nitrogen-dye laser system. The excitation spectrum exhibits two vibrational
components (v'<--v''=0) highly broadened by means of unresolved rotational
structure and some additional contributions of "hot-bands" components (v'<-
v''=1). The last effect is due to an extremely small separation of the
vibrational levels in the ground X(1)0+ state of the CdHe molecule, where v'=0
vibrational level is separated from v''=0 by merely 6.0 cm(-1). It follows
therefore that even in an extremely cold environment (T(v) approximately 10K) of
a jet-expansion beam the population of v''=1 level is feasible, due to some
residual collisions, and hence the v'<--v'=1 transitions are highly probable. The
assignment of vibrational bands and numerical analysis of the spectrum was based
and obtained with the aid of a rigorous computer simulation of the C(1)1<--X(1)0+
transition including the impact of rotational structure and hot-bands
contributions. As a result we obtained optical potential parameters of the
C(1)1(5(1)P(1)) state of CdHe molecule which are further discussed in terms of
our recent (and only existing) experimental results regarding the X(1)0+,
B1(5(3)P(1)) and A0+(5(3)P(1)) states of CdHe as well as in terms of ab initio
calculations results.
PMID- 17029944
TI - Spectroscopic studies of charge transfer complexes between colchicine and some pi
acceptors.
AB - Charge transfer complexes between colchicine as donor and pi acceptors such as
tetracyanoethylene (TCNE), 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), p
chloranil (p-CHL) have been studied spectrophotometrically in dichloromethane at
21 degrees C. The stoichiometry of the complexes was found to be 1:1 ratio by the
Job method between donor and acceptors with the maximum absorption band at a
wavelength of 535, 585 and 515 nm. The equilibrium constant and thermodynamic
parameters of the complexes were determined by Benesi-Hildebrand and van't Hoff
equations. Colchicine in pure form and in dosage form was applied in this study.
The formation constants for the complexes were shown to be dependent on the
structure of the electron acceptors used.
PMID- 17029945
TI - Heteroleptic tris-chelates of ruthenium(II): synthesis, spectral characterisation
and electrochemical properties.
AB - A facile reaction of cis-trans-cis-RuCl(2)(RaaiR')(2) [RaaiR'=1-alkyl-2
(arylazo)imidazole, m-R-C(6)H(4)-NN-C(3)H(2)-NN-1-R', where R=H (a), OMe (b),
NO(2) (c) and R'=Me (1), Et (2) and CH(2)Ph (3)] either with 2,2'-bipyridine
(bpy) and AgNO(3) followed by NaClO(4) or [Ag(bpy)(2)](ClO(4)) in boiling acetone
has isolated red-brown [Ru(bpy)(RaaiR')(2)](ClO(4))(2) (1a-c, 2a-c, 3a-c). The
maximum molecular peak of [Ru(bpy)(OMeaaiMe)(2)](ClO(4))(2) (1b) is observed at
m/z 888.01 (100%) in the FAB mass spectrum. IR spectra of the complexes show CN
and NN stretching at 1590 and 1370cm(-1) which is red shifted by 40 and 90cm(-1)
from the free ligand value supports Ru-azo nitrogen pi bonding interaction. The
emission spectra in frozen glass (77K) are sharper and considerably more intense
than the room temperature spectra. The (1)H NMR spectral measurements suggest
methylene, -CH(2)-, in RaaiEt gives a complex AB type multiplet while in
RaaiCH(2)Ph it shows AB type quartets. Considering two arylazoimidazole moieties
there are 20 different carbon atoms in the molecule which gives a total of 20
different peaks in the (13)C NMR spectrum. In the (1)H-(1)H COSY spectrum of the
present complexes, absence of any off-diagonal peaks extending from delta=14.12
and 9.55ppm confirm their assignment of no proton on N(1) and N(3), respectively.
Contour peaks in the (1)H-(13)C HMQC spectrum in the present complexes, the
absence of any contours at delta=147.12, 160.76, 155.67 and 157.68 ppm assign
them to the C(2), C(6), C(8) and C(e and e'') carbon atoms, respectively. Cyclic
voltammogram shows Ru(III)/Ru(II) redox couple along with three successive ligand
reductions. The plot of difference in potential of first oxidation and reduction
versus energy of main MLCT band (nu(CT)) is linear. Electrochemical
parametrisation of Ru(III)/Ru(II) redox couple determines ligand potential
E(L)(L).
PMID- 17029946
TI - Assessment of ternary iron-cyclodextrin-2-naphthol complexes using NMR and
fluorescence spectroscopies.
AB - Recent research has indicated that ternary complexes can be formed among
carboxymethyl-beta-cyclodextrin, certain polycyclic aromatic hydrocarbons (PAHs)
(e.g. anthracene and 2-naphthol), and Fe(2+) in aqueous solution. The formation
of these ternary complexes has been suggested as the reason for improved reaction
efficiency in iron catalyzed Fenton degradation (H(2)O(2)+Fe(2+)-->*OH+OH(
)+Fe(3+)) of PAHs and other pollutants. In the present work, several other
cyclodextrins were examined to determine their ability to form similar ternary
complexes with 2-naphthol and Fe(2+). Fluorescence and NMR techniques were
employed in this study. Results showed that hydroxypropyl-beta-cyclodextrin, beta
cyclodextrin, and alpha-cyclodextrin were able to encapsulate 2-naphthol
molecules, but their binding with Fe(2+) was weak. On the contrary, sulfated-beta
cyclodextrin has significant binding with Fe(2+), but it showed little inclusion
of 2-naphthol molecules. Consequently, none of these four cyclodextrins formed
significant amounts of ternary complexes in aqueous solution. The techniques used
in this study provide useful methods for assessing the ability of cyclodextrins
to form ternary complexes with guest compounds and metal ions.
PMID- 17029947
TI - Spectral properties of some metal complexes derived from uracil-thiouracil and
citrazinic acid compounds.
AB - The reaction of FeCl(3) with uracil (H(2)L(1)), citrazinic acid (H(2)L(6)), 5
(phenylazo)citrazinic acid (H(2)L(7)), 5-(m-hydroxyphenylazo)citrazinic acid
(H(2)L(8)) and 5-(m-nitrophenylazo)citrazinic acid (H(2)L(9)) leads to the
formation of complexes with the empirical formula Fe(HL)(3).nH(2)O (n=1-3). All
of the prepared complexes have octahedral complexation geometry where the azo
group is not the reactive site for complexation. Thiouracil (H(2)L(2)) and the 5
(substituted phenylazo)thiouracil (H(2)L(3)-H(2)L(5)) ligands are bidentates on
complexation with Co(II), Ni(II) and Cu(II). The complexes have been
characterized by elemental analyses, IR, electronic spectra, magnetic
susceptibility, DTA, electron spin resonance (copper complexes) and Mossbauer
spectra (iron complexes). The coordination bond lengths between the metal ion and
the active centers for complexation were calculated.
PMID- 17029948
TI - Hormonal effects on the secretion and glycoform profile of corticosteroid-binding
globulin.
AB - Corticosteroid-binding globulin (CBG) is a plasma glycoprotein that is primarily
synthesized in the liver and binds cortisol and progesterone with high affinity.
In this study, a CBG secreting hepatocellular carcinoma derived cell line (HepG2)
was used to investigate the hormonal regulation of hepatic CBG synthesis. HepG2
cells were grown for 72 h in 30, 300 and 3000 nM concentrations of estradiol
(E2), testosterone (T), insulin, thyroxin (T4) and dexamethasone (DMZ) and the
secreted CBG quantified by a novel enzyme-linked immunosorbent assay (ELISA). Two
dimensional polyacrylamide gel electrophoresis (2D-PAGE) was carried out to
determine the effects of these hormones on the relative distribution of CBG
glycoforms. Insulin, T4 and high concentrations of E2 decreased the secretion of
CBG by HepG2 cells (p<0.05). Ethanol, the solvent used for E2, T and DMZ, also
significantly attenuated CBG secretion. 2D-PAGE resolved 13-14 glycoforms of CBG
produced by HepG2 cells. Insulin caused a reduction in the synthesis of more
acidic, while T4 and DMZ decreased the production of more basic CBG glycoforms.
Stimulation with E2 resulted in the synthesis of additional isoforms of increased
acidity, which may represent a type of CBG only seen during pregnancy in vivo.
Possible physiological implications of these findings are discussed.
PMID- 17029949
TI - Theta burst stimulation does not reliably depress all regions of the human motor
cortex.
AB - OBJECTIVE: The excitability of the human motor cortex projecting to hand muscles
can be reduced by theta burst transcranial magnetic repetitive stimulation (TBS).
This study compared the magnitude and variability of changes evoked by TBS for a
distal and proximal arm muscle. METHODS: Eight subjects participated in three
studies. In each study, electromyographic responses (MEPs) to single-pulse
transcranial magnetic stimulation assessed cortical excitability before and after
40s of TBS. In the first two studies, TBS (intensity, 80% active motor threshold)
was delivered to the optimal locations for biceps or first dorsal interosseous
(FDI). In the final study, weaker intensity TBS was delivered over the biceps
representation. RESULTS: TBS targeting biceps produced highly variable results
among subjects. For the group, MEPs were not significantly depressed. Repeat
studies in individual subjects highlighted the variability of responses. For FDI,
MEPs were significantly depressed 5min after TBS and remained depressed for
>30min (p<0.05). No significant changes in biceps MEPs occurred with weaker TBS.
CONCLUSIONS: The magnitude and reliability of TBS depends on the region of the
cortex targeted. SIGNIFICANCE: Results obtained for the hand should not be
considered indicative of changes that will occur in other regions of the motor
cortex or the brain.
PMID- 17029950
TI - Propagation of interictal discharges in temporal lobe epilepsy: correlation of
spatiotemporal mapping with intracranial foramen ovale electrode recordings.
AB - OBJECTIVE: We have investigated intracerebral propagation of interictal
epileptiform discharges (IED) in patients with mesial temporal lobe epilepsy
(MTLE) by using spatiotemporal source maps based on statistical nonparametric
mapping (SNPM) of low resolution electromagnetic tomography (LORETA) values.
METHODS: We analyzed 30 patterns of IED recorded simultaneously with scalp and
intracranial foramen ovale (FO) electrodes in 15 consecutive patients with
intractable MTLE. The scalp EEG signals were averaged time-locked to the peak
activity in bilateral 10-contact FO electrode recordings. SNPM was applied to
LORETA values and spatiotemporal source maps were created by allocating the t
values over time to their corresponding Brodmann areas. Propagation was defined
as secondary statistically significant involvement of distinct cortical areas
separated by >15 ms. The results were correlated with intracranial data obtained
from FO electrode recordings and with scalp EEG recordings. All patients
underwent subsequent amygdalo-hippocampectomy and outcome was assessed one year
after surgery. RESULTS: We found mesial to lateral propagation in 6/30 IED
patterns (20%, four patients), lateral to mesial propagation in 4/30 IED patterns
(13.3%, four patients) and simultaneous (within 15 ms) activation of mesial and
lateral temporal areas in 6/30 IED patterns (20%, five patients). Propagation
generally occurred within 30 ms and was always limited to ipsilateral cortical
regions. Nine/30 IED patterns (30%) showed restricted activation of mesial
temporal structures and no significant solutions were found in 5/30 IED patterns
(16.7%). There was no clear association between the number or characteristics of
IED patterns and the postsurgical outcome. CONCLUSIONS: Spatiotemporal mapping of
SNPM LORETA accurately describes mesial to lateral temporal propagation of IED,
and vice versa, which commonly occur in patients with MTLE. SIGNIFICANCE:
Intracerebral propagation must be considered when using non-invasive source
algorithms in patients with MTLE. Spatiotemporal mapping might be useful for
visualizing this propagation.
PMID- 17029951
TI - The influence of Mozart's music on brain activity in the process of learning.
AB - OBJECTIVE: The study investigated the influence Mozart's music has on brain
activity in the process of learning. A second objective was to test priming
explanation of the Mozart effect. METHODS: In Experiment 1 individuals were first
trained in how to solve spatial rotation tasks, and then solved similar tasks.
Fifty-six students were divided into 4 groups: a control one--CG who prior to and
after training relaxed, and three experimental groups: MM--who prior to and after
training listened to music; MS--who prior to training listened to music and
subsequently relaxed; and SM--who prior to training relaxed and afterward
listened to music. The music used was the first movement of Mozart's sonata (K.
448). In Experiment 2, thirty-six respondents were divided into three groups: CG,
MM (same procedure as in Experiment 1), and BM--who prior to and after training
listened to Brahms' Hungarian dance No. 5. In both experiments the EEG data
collected during problem solving were analyzed using the methods of event-related
desynchronization/synchronization (ERD/ERS) and approximated entropy (ApEn).
RESULTS: In the first experiment the respondents of the MM, MS, and SM groups
showed a better task-performance than did the respondents of the CG group.
Individuals of the MM group displayed less complex EEG patterns and more alpha
band synchronization than did respondents of the other three groups. In
Experiment 2 individuals who listened to Mozart showed a better task performance
than did the respondents of the CG and BM groups. They displayed less complex EEG
patterns and more lower-1 alpha and gamma band synchronization than did the
respondents of the BM group. CONCLUSIONS: Mozart's music, by activating task
relevant brain areas, enhances the learning of spatio-temporal rotation tasks.
SIGNIFICANCE: The results support priming explanation of the Mozart effect.
PMID- 17029952
TI - H-reflex depression by propofol and sevoflurane is dependent on stimulus
intensity.
AB - OBJECTIVE: The H-reflex has been widely used to investigate effects of drugs on
motoneuron excitability in humans. However, up to now no systematic investigation
has been done to examine the effects at different stimulus intensities. Here, the
M. soleus recruitment curves were compared under influence of propofol and
sevoflurane with control conditions to investigate these stimulus intensity
dependent effects. METHODS: The study was performed in 10 volunteers for propofol
and sevoflurane each, aged 23-32 years. The M. soleus H-reflex was evoked by
stimulation of the tibial nerve. Recruitment curves were gained by increasing the
stimulation current stepwise from below the threshold of a minimal H-reflex up to
a maximal (m-response. Measurements were performed under the influence of the
respective drug (2mg/l propofol, 0.8 vol% sevoflurane) and compared to control
measurements before and after drug administration. RESULTS: The relative amount
of depression of the H-reflex at high stimulus intensities is for both drugs
significantly (p<0.001, Friedman's test) lower than at low stimulus intensities.
CONCLUSIONS: Stimulus dependent effects have to be taken into consideration when
experimental settings to investigate the effects of drugs on the H-reflex are
being designed. According to the size principle of motoneuron excitation, it can
also be assumed that under the influence of propofol and sevoflurane larger
motoneurons are not depressed in the same amount as smaller motoneurons.
SIGNIFICANCE: Different drug effects on the H-reflex at different stimulus
intensities are not only of methodological importance, but also indicate
different drug effects on motoneurons of different sizes.
PMID- 17029953
TI - Effects of GPi stimulation on human thalamic neuronal activity.
AB - OBJECTIVE: Determine the effects of globus pallidus interna (GPi) deep brain
stimulation (DBS) on ventral oralis posterior nucleus of the thalamic (Vop)
neuronal activity. METHODS: Microelectrode recordings in Vop during high
frequency DBS GPi in a patient with dystonia. RESULTS: Twelve (48%) of 25 neurons
in five locations neurons decreased their average discharge frequency, 2 (8%)
increased and 11(44%) demonstrated no overall change. The patterns of responses
were complex with periods of increase and decreased activity. All neurons were
inhibited for the time period 3.5-5ms following the DBS pulse. Eighty-eight
percent of neurons showed brief but highly consistent increases in the first 1ms
following stimulation, 52% showed increased activities from 1.5 to 3ms. Twenty
four percent of neurons increased activity following inhibition. CONCLUSIONS:
These findings are consistent with DBS activation of GPi axons to Vop and
probable antidromic activation of Vop axons. SIGNIFICANCE: The physiological
effects of DBS are far more complicated and will escape any theory that does not
address the mechanisms of DBS as stimulation of a complex network of
interactions. Further, the findings of post-inhibitory rebound increased raises
questions about the role in inhibition in the current concepts of basal ganglia
physiology.
PMID- 17029954
TI - Extended BSI for continuous EEG monitoring in carotid endarterectomy.
AB - OBJECTIVE: Carotid endarterectomy is a common procedure as a secondary prevention
of stroke, and is often performed with selective shunting. Although various EEG
parameters have been proposed to determine if the brain is at risk during carotid
artery clamping, the common procedure is still the visual assessment of the EEG.
Here, we propose an extension to the previously described brain symmetry index
(BSI) [van Putten M, Peters J, Mulder S, de Haas J, Bruijninckx C, Tavy D. A
brain symmetry index (BSI) for online EEG monitoring in carotid endarterectomy.
Clin Neurophysiol 2004, 115(5), 1189-94.], as an additional quantitative
criterion for shunt need in carotid endarterectomy. METHODS: An extension of the
Brain Symmetry Index was implemented to capture both spatial (hemispheric) (sBSI)
and temporal changes (tBSI) in the EEG. In this pilot study, the method is
exemplified by simulation and by application to EEG records from 25 patients who
underwent a carotid endarterectomy. RESULTS: Simulations show that hemispheric
asymmetry is captured by changes in sBSI, only, while temporal symmetry changes,
not due to changes in hemispheric asymmetry, are reflected by changes in tBSI.
Combinations of changes induced changes in both parameters. This was confirmed by
analysis 25 EEG records. Unilateral EEG changes during test-clamping are
reflected by DeltasBSI>0.05, diffuse changes by DeltatBSI>0.02 and combinations
by simultaneous changes in both features. CONCLUSIONS: In this pilot study, we
present a doublet of quantitative EEG features, that in principle detects any
change in the spectral characteristics of the EEG, decomposing the changes into a
measure that captures spatial symmetry changes (sBSI), and a measure that
quantifies diffuse temporal changes, that are not due to changes in spatial
symmetry (tBSI). Both features are normalized with values ranging from [0-1], and
can easily be implemented on-line to support the visual analysis of the EEG in
the decision for selective shunting. SIGNIFICANCE: Quantitative real-time EEG
analysis will assist in the EEG interpretation for selective shunting in carotid
endarterectomy.
PMID- 17029955
TI - Voltage sources in mesial temporal lobe epilepsy recorded with foramen ovale
electrodes.
AB - OBJECTIVE: We introduce a monopole model to examine the sources of ictal and
interictal activity in mesial temporal lobe epilepsy (MTLE) recorded using
foramen ovale electrodes (FOE). METHODS: Classical electrostatic theory was
applied to derive mathematical expressions. Interictal and ictal activity was
acquired using FOE and scalp video-electroencephalography (v-EEG) during awake
and sleep states. A total of 2057 interictal spikes and 712 ictal spikes were
analyzed. Thirty-five seizures from several consecutive episodes were examined.
MRI and clinical data were correlated with voltage source localization. RESULTS:
Patients (20) were grouped according to the spatial distribution of voltage
sources of interictal activity. Voltage sources were located over 3.4 and 21.6mm
in the anterior-to-posterior axis of mesiotemporal structures and separated no
more than 7 mm from this axis. In most patients (16), sources were restricted to
11.1+/-1.5mm, whereas other patients (4) exhibited a wider distribution (29.6
43.5mm). Sources of ictal and interictal activity partially overlapped, with
ictal sources exhibiting a posterior localization at 20-40 mm. Both interictal
and ictal sources were anterior to MRI atrophy. No difference between awake and
sleep states were found, neither correlation between source scattering and
history of epilepsy. CONCLUSIONS: Voltage source analysis applied to FOE suggests
that, in most MTLE patients, interictal activity emerges from very restricted
areas. Some patients, however, exhibited sources which are distributed all along
the mesiotemporal structures. Our data suggest an anterior-to-posterior alignment
of the irritative, ictal and atrophic zones. SIGNIFICANCE: The voltage source
model applied to FOE can help to map the extension of the irritative and ictal
areas in mesiotemporal structures.
PMID- 17029956
TI - Altered diurnal autonomic variation and reduced vagal information flow in acute
schizophrenia.
AB - OBJECTIVE: This study aimed to further investigate autonomic function in
schizophrenic patients using long-term electrocardiographic (ECG) recordings.
METHODS: Twenty unmedicated patients suffering from an acute episode of paranoid
schizophrenia and 20 matched control subjects were recruited and 24-h ambulatory
electrocardiograms were recorded. In order to investigate complexity of heart
rate fluctuations related to different physiological time scales, linear heart
rate variability (HRV) as well as autonomic information flow (AIF) parameters
were calculated from day and night time intervals. RESULTS: While heart rates
were increased, root mean successive square difference (RMSSD), a measure for
vagal function as well as standard deviation of 5-min mean NN-intervals (SDANN),
reflecting parasympathetic and sympathetic tone, were decreased in schizophrenia.
Furthermore, a decrease of vagal information flow was apparent during night time
(decreased mean high frequency peak decay (PD(mHF))). In addition, increased
INT(NN) (area under the AIF curve) as well as decreased beat decay (BD(NN)) and
mean very low frequency PD (PD(mVLF)) indicated reduced complexity in patients
during day and night time. CONCLUSIONS: HRV and AIF parameters indicate altered
diurnal autonomic variation in schizophrenia. SIGNIFICANCE: Reduced vagal
modulation and loss of complexity might both contribute to the increased risk for
sudden cardiac death in schizophrenia.
PMID- 17029957
TI - Effect of pretreatment severity on xylan solubility and enzymatic breakdown of
the remaining cellulose from wheat straw.
AB - The effect of process conditions used for wheat straw pretreatments on the liquor
and residue-composition was studied. Hereto, the pretreatment conditions were
expressed in a 'combined severity R(0)(')-factor'. The higher the combined
severity factor (R(0)(')) the more xylan was released from the wheat straw, but
the more xylan decomposed and furfural formation occurred. The percentage of
residual xylan present after pretreatment appeared to be a good indicator
concerning cellulose degradability or bio-ethanol production. Namely, cellulose
degradation by using commercial enzymes was higher at higher severities
corresponding to a lower amount of residual xylan. The xylan release and
degradation was studied in more detail by using HPSEC and MALDI-TOF mass
spectrometry. The more severe the treatment the more (acetylated) xylose
oligomers with a DP lower than nine were analysed. The presence of (acetylated)
xylans with a DP of 9-25 increased slightly from low to medium severity. The
quantification of the DP-distribution of the (acetylated) xylans released proved
to be a good tool to predict cellulose degradability.
PMID- 17029958
TI - Toluene mineralization by denitrification in an up flow anaerobic sludge blanket
(UASB) reactor.
AB - In order to examine the effect of easily degradable substrate such as acetate on
toluene mineralization by denitrification, an upflow anaerobic sludge blanket
(UASB) reactor in steady state was set up. The experimentation was carried out in
two stages. Initially, the reactor was fed with a carbon loading rate of 250 mg
acetate-C L-1 d-1 as electron source. Nitrate loading rate (mg ) was adjusted to
obtain a constant C/N ratio of 1.4. In the second stage, five toluene-C loading
rates (TLR, mg toluene-C L-1 d-1), 25, 50, 75, 100 and 125, were assessed while
total carbon loading rate and C/N were maintained constant at 250 mg C L-1 d-1
and 1.4, respectively. In so doing, acetate-C loading rate (mg acetate-C L-1 d-1)
was gradually substituted by toluene-C. When acetate-C was the only electron
source a dissimilative denitrifying process resulted as indicated by bicarbonate
yield YHCO3, mg produced/mg carbon consumed) of 0.74 +/- 0.005 and denitrifying
yield (YN2, mg N2 produced/mg consumed) of 0.89 +/- 0.042. The addition of
different TLR did not affect the biological process as consumption carbon
efficiency (CCE) values remained up to 95% +/- 3.5 and YHCO3 and YN2 values were
higher than 0.71 +/- 0.03 and 0.88 +/- 0.01, respectively. Toluene mineralization
by denitrification in continuous culture was successfully achieved. A simple UASB
denitrifying reactor system has promising applications for complete conversion of
nitrate, toluene and acetate into N2 and CO2 with a minimal sludge production.
PMID- 17029959
TI - Effects of combined deferiprone and desferrioxamine iron chelating therapy in
beta-thalassemia major end-stage heart failure: a case report.
AB - Despite usual iron chelating therapy based on desferrioxamine, patients affected
by beta-thalassemia major (beta-TM) often develop progressive heart failure
caused by myocardial iron overload, which is the leading cause of mortality
within the third decade of life. Heart transplantation is a limited therapeutic
option, as very often these patients have multi-organ iron deposits and infective
complications (particularly hepatitis C), secondary to frequent blood
transfusions. We report the case of a 26-year-old male affected by beta-TM with
end-stage heart failure, who showed a dramatic improvement in symptoms and
myocardial function when a new oral iron chelating agent, deferiprone, was added
to standard therapy with desferrioxamine.
PMID- 17029960
TI - Tibial translation in exercises used early in rehabilitation after anterior
cruciate ligament reconstruction exercises to achieve weight-bearing.
AB - Accelerated rehabilitation after ACL reconstruction involves early weight
bearing. Exercises designed to achieve weight-bearing should be effective for the
neuromuscular system and protect the knee from excessive anterior tibial
translation. The aim of this study was to assess the anterior tibial translation
under two different body-weight shift exercises at 2 weeks post-ACL
reconstruction and compare this with healthy controls. METHODS: Seven patients at
2 weeks after ACL reconstruction and seven controls participated in the study.
Dynamic sagittal tibial translation was registered during two body weight shift
exercises (from side to side and forward-backward). RESULTS: There was no
significant difference in maximal translation between the two exercises in the
ACL-reconstructed group. In the control group, the body weight shift from side-to
side exercise resulted in larger anterior translation compared to the forward
backward body weight shift. CONCLUSIONS: Two weeks after ACL reconstruction, both
body weight shift exercises can be used to train body weight acceptance.
PMID- 17029961
TI - Hemilaterally symptomatic bipartite patella associated with bone erosions arising
from a gouty tophus: a case report.
AB - Symptomatic bipartite patella in adults is rare. We have treated an unusual case
of a bipartite patella in an adult, which became symptomatic in association with
cystic degeneration localized to the patella and a gouty tophus. Although the
patient had bilateral bipartite patellae, multiplanar reformation with computed
tomography (CT-MPR) clearly demonstrated that the bipartite portion of the
patella was malaligned at the junction of the accessory bone and patella in the
symptomatic knee. Bone erosions were present both in the bipartite fragment and
adjacent portion of the patella. After surgical excision of the bipartite
fragment, the patient's symptoms have improved. This case illustrates that cyst
formation associated with inflammatory arthritis may be a rare cause for a
bipartite patella in an adult to become symptomatic.
PMID- 17029962
TI - From insects to human hosts: Identification of major genomic differences between
entomopathogenic strains of Photorhabdus and the emerging human pathogen
Photorhabdus asymbiotica.
AB - Pathogenic bacteria of the genus Photorhabdus are naturally found in symbiotic
association with soil entomopathogenic nematodes, and are of increasing economic
interest in view of their potential for the development of novel biopesticides.
This bipartite natural system is currently used for the biological control of
crop pests in several countries. However, an increasing number of Photorhabdus
strains have recently been isolated from human clinical specimens in both the
United States and Australia, associated with locally invasive soft tissue
infections and disseminated bacteraemia. In view of their growing use in
biological control, which increases the potential rate of exposure of humans to
these pathogens, we decided to undertake a comparative study of the genomic
differences between insect and human pathogenic strains of Photorhabdus, in an
attempt to understand the genetic mechanisms involved in the apparent change of
host specificity, presumably responsible for their recently acquired capacity to
infect humans. The data presented here demonstrates that major genomic
differences exist between strains of Photorhabdus exhibiting virulence against
insects or humans. Several individual genes, coding for virulence factors, were
isolated and shown to be specific to the Photorhabdus asymbiotica human
pathogens. One of these genes, sopB, encoding a host cell invasion factor
translocated via the type III secretion system, has been cloned and the
comparison of its genomic context in different pathogens strongly indicates that
horizontal gene transfer is implicated in the acquisition of these virulence
factors specific to the human pathogens. The precise role of this and other
virulence factors identified here in the pathogenicity of P. asymbiotica towards
humans is currently under investigation.
PMID- 17029963
TI - PlasmoDB v5: new looks, new genomes.
AB - Version 5.1 of PlasmoDB, a resource for malaria parasite genomic and functional
genomics datasets, was released in August 2006. This new release includes
additional Plasmodium genomes and a newly designed website. The new site reflects
the status of PlasmoDB as a member of a linked family of Apicomplexan databases.
PMID- 17029964
TI - Modern approaches to a rapid diagnosis of tuberculosis: promises and challenges
ahead.
AB - The limitations of the conventional methods for diagnosing tuberculosis have
spurred multi-faceted research activities in this field throughout the world.
Chromatographic methods appear promising but may not be widely available in the
developing countries. Immuno-diagnostic methods using combinations ("cocktails")
of antigens have high sensitivity and specificity and can easily be applied in
the peripheral laboratories and in the field settings. Though expensive,
molecular methods for diagnosis of tuberculosis have advantages of speed,
sensitivity, and specificity. Adequate training of the eligible personnels in
molecular methods and prevention of laboratory-dependent contamination may help
reduce false positive results. Although, there are no clear guidelines, so far on
how to make out the best from the gene amplification methods, yet their use may
be encouraged with adequate quality controls, because of the inherent ingenuity
and promises of these methods. Phage-based molecular methods provide rapid
results in susceptibility tests for anti-tubercular drugs. In future, many
sophisticated techniques are expected to hit the market for a rapid diagnosis of
tuberculosis. In the developing countries, it is necessary to evaluate
availability of suitable infrastructure and trained personnels before adopting
modern diagnostic methods.
PMID- 17029968
TI - Comparison between fluorimetry and oximetry techniques to measure photosynthesis
in the diatom Skeletonema costatum cultivated under simulated seasonal
conditions.
AB - This study reports comparison of two techniques measuring photosynthesis in the
ubiquitous diatom Skeletonema costatum, i.e., the classical oximetry and the
recent modulated fluorimetry. Microalgae in semi-continuous cultures were exposed
to five different environmental conditions simulating a seasonal effect with co
varying temperature, photoperiod and incident light. Photosynthesis was assessed
by gross rate of oxygen evolution (P(B)) and the electron transport rate (ETR)
measurements. The two techniques were linearly related within seasonal treatments
along the course of the P/E curves. The light saturation intensity parameters (Ek
and Ek(ETR)), and the maximum electron transport rate increased significantly
with the progression of the season while the maximum light utilization efficiency
for ETR (alpha(ETR)) was constant. By contrast, the maximum gross oxygen
photosynthetic capacity (Pmax(B)) and the maximum light utilization efficiency
for P(B) (alpha(B)) increased from December to May treatment but decreased from
May to July treatment. Both techniques showed clear photoacclimation in
microalgae with the progression of the season, as illustrated by changes in
photosynthetic parameters. The relationship between the two techniques changed
when high temperature, photoperiod and incident light were combined, possibly due
to an overestimation of the PAR--averaged chlorophyll-specific absorption cross
section. Despite this change, our results illustrate the strong suitability of in
vivo chlorophyll fluorimetry to estimate primary production in the field.
PMID- 17029965
TI - CRE-mediated transcription and COX-2 expression in the pilocarpine model of
status epilepticus.
AB - Status epilepticus (SE) triggers neuronal death, reactive gliosis and remodeling
of synaptic circuitry, thus leading to profound pathological alterations in CNS
physiology. These processes are, in part, regulated by the rapid upregulation of
both cytotoxic and cytoprotective genes. One pathway that may couple SE to
transcriptionally dependent alterations in CNS physiology is the CREB (cAMP
response element-binding protein)/CRE (cAMP response element) cascade. Here, we
utilized the pilocarpine model of SE on a mouse strain transgenic for a CRE
reporter construct (beta-galactosidase) to begin to characterize how seizure
activity regulates the activation state of the CREB/CRE pathway in both glia and
neurons of the hippocampus. SE triggered a rapid (4-8 h post-SE) but transient
increase in CRE-mediated gene expression in the neuronal sublayers. In contrast
to neurons, SE induced a lasting increase (up to 20 days) in CRE-mediated
transcription in both reactive astrocytes and microglia. CRE-mediated gene
expression correlated with expression of the pro-inflammatory enzyme
cyclooxygenase-2 (COX-2). To examine the role of CREB in SE-induced COX-2
expression, we generated a transgenic mouse strain that expresses A-CREB, a
potent repressor of CREB-dependent transcription. In these animals, the capacity
of SE to stimulate COX-2 expression was markedly attenuated, indicating that CREB
is a key intermediate in SE-induced COX-2 expression. Collectively these data
show that SE triggers two waves of CREB-mediated gene expression, a transient
wave in neurons and a long-lasting wave in reactive glial cells, and that CREB
couples SE to COX-2 expression.
PMID- 17029969
TI - Ultrastructural and autoradiographical analysis show a faster skin repair in He
Ne laser-treated wounds.
AB - There are evidences that low-intensity red laser radiation is capable to
accelerate wound healing. Nowadays, this therapy has been gradually introduced in
clinical practice although mechanisms underlying laser effects are poorly
understood. To better understand the photobiological effects of laser radiation,
this study investigated by electron microscopy, immunohistochemistry and
autoradiography the morphological and functional features of irradiated and none
irradiated injured mice skin. Full-thickness skin lesions were created on the
back of mice and irradiated on days 1, 5, 8, 12, and 15 post-wounding with a He
Ne laser (lambda=632.8nm), dose 1J/cm(2), exposure time 3min. Non-irradiated
lesions were used as a control. The mice were inoculated with (3)H-proline and
sacrificed one hour after on the 8th, 15th and 22nd days to histological and
radioautographical analysis. The irradiated-lesions showed a faster
reepithelization compared with control lesions. The irradiated dermis contained a
higher number of activated fibroblasts compared to control group and, most of
them showed several cytoplasmic collagen-containing phagosomes. In irradiated
lesions, smooth muscle alpha-actin positive cells predominated, which correspond
to a higher number of myofibroblasts observed in the electron microscope.
Moreover, laser radiation reduced the local inflammation and appears to influence
the organization of collagen fibrils in the repairing areas. Quantitative
autoradiography showed that the incorporation of (3)H-proline was significantly
higher in irradiated-dermis on the 15th day post-wounding (p<0.05). These results
suggest that laser radiation may accelerate cutaneous wound healing in a murine
model.
PMID- 17029966
TI - Autoimmunity versus tolerance: can dying cells tip the balance?
AB - Apoptosis is a physiological process of self-destruction for cells that are
damaged or programmed to die. Apoptosis occurs through a series of regulated
events that allow cellular debris to be contained and efficiently phagocytosed
without initiating a proinflammatory immune response. Recent data have linked
physiological apoptosis and the uptake of apoptotic cells by macrophages and some
subsets of dendritic cells to the maintenance of peripheral immune tolerance.
However, when cells die through necrosis, spilling their intracellular contents,
or are infected with various pathogens, activation of antigen-presenting cells
and induction of an immune response can occur. Receptors for extrinsic pathogen
associated structures, such as membrane bound Toll-like receptors (TLRs) or
intracellular Nod-like receptors (NLRs) can also respond to cross-reactive host
molecules from dying cells and may focus autoimmune responses onto these
antigens. Several autoimmune disorders have been linked to defects in the
apoptotic process. Defective apoptosis of immune cells leads to autoimmunity, as
in autoimmune lymphoproliferative syndrome (ALPS) associated with mutations in
the death receptor Fas. Defective clearance of apoptotic cell debris can also
lead to autoantibody production. We will discuss how cell death and apoptotic
cell clearance may affect the finely tuned balance between peripheral immune
tolerance and autoimmunity.
PMID- 17029970
TI - Phytochrome-like responses in Euglena: A low fluence response that reorganizes
the spectral dependence of the high irradiance response in long-day photoperiodic
induction of cell division.
AB - Irradiance spectra change spatiotemporally, and angiosperms adapt accordingly,
mainly through phytochromes. This study challenges the long-held belief that the
flagellated alga Euglena gracilis lacks phytochromes and is therefore unaffected
by spectral changes. We photoautotrophically cultured the alga under continuous
light (LL), then transferred it to darkness. After about 26h in darkness,
different irradiations for 3h enabled cell division in dark-arrested G2 cells
evoking a high-irradiance response (HIR). The spectral characteristics of the
irradiation during the LL period (pre-irradiation) defined the spectral
sensitivity in the subsequent dark period. LL with light rich in the red spectrum
led to a HIR to the red spectrum (R-HIR), whereas light rich in the far-red
spectrum (FR) led to a FR-HIR. Finishing the period of pre-irradiation consisting
of continuous cool-white fluorescent light (rich in R) by a FR pulse enhanced the
characteristics of the FR-HIR 26h later. By contrast, a R pulse given at the end
of the pre-irradiation rich in FR potentiated the R-HIR. The effects were
completely photoreversible between R and FR with critical fluences of about
2mmolm(-2), satisfying the classic diagnostic feature of phytochromes. The action
spectrum of the FR effect at the end of pre-irradiation consisting of continuous
cool-white fluorescent light (rich in R) had a main peak at 740nm and a minor
peak at 380nm, whereas antagonization of the FR effect had a main peak at 640nm
and a minor peak at 480nm. Wavelengths of 610 and 670nm appeared in both spectra.
We also demonstrated the photoreversibility of 380/640, 480/740, and (610 and
670)/(640 and 740) nm. We conclude that Euglena displays phytochrome-like
responses similar to the 'shade avoidance' and 'end-of-day FR' effects reported
in angiosperms.
PMID- 17029971
TI - High irradiance responses involving photoreversible multiple photoreceptors as
related to photoperiodic induction of cell division in Euglena.
AB - Little is known about the photoreceptors involved in the photoperiodism of
unicellular organisms, which we elucidated by deriving their action spectra. The
flagellated alga Euglena gracilis exhibits photoperiodism, with a long-day
response in cell reproduction. The underlying clock is a circadian rhythm with
photoinductive capability, peaking at subjective dusk and occurring at the 26th
hour in continuous darkness (DD) when transferred from continuous light (LL); it
regulates photoinduction, a high-irradiance response (HIR), of a dark-capability
of progressing through cell division. We derived the action spectra by
irradiating E. gracilis with monochromatic light for 3h at around the 26th hour;
the action maxima occurred at 380, 450-460, 480, 610, 640, 660, 680, and 740nm.
Except for the maximum at 450-460nm, which was always a major maximum, the maxima
greatly depended on the red (R)/far-red (FR) ratio of the prior LL. The high R/FR
ratio resulted in a dominant major peak at 640nm and minor peaks at 480 and
680nm, whereas the low ratio resulted in dominant major peaks at 610 and 740nm
and minor peaks at 380 and 660nm; the critical fluence was minimally about
60mmolm(-2). These HIRs resulted from the accumulation of corresponding low
fluence responses (LFRs) because we found that repetition of a 3-min light/dark
cycle, with critical fluences of 1mmolm(-2), lasting for 3h resulted in the same
photoinduction as the continuous 3-h irradiation. Moreover, these LFRs expressed
photoreversibility. Thus, photoperiodic photoinduction involves Euglena
phytochrome (640 and 740nm) and blue photoreceptor (460nm). Although 380, 480,
610, 660, and 680nm may also represent Euglena-phytochrome, a definite conclusion
awaits further study.
PMID- 17029972
TI - Color of illumination during growth affects LHCII chiral macroaggregates in pea
plant leaves.
AB - To determine whether the color of illumination under which plants are grown,
affects the structure of photosynthetic antennae, pea plants were grown under
either blue-enriched, red-enriched, or white light. Carotenoid content of
isolated chloroplasts was found to be insensitive to the color of illumination
during growth, while chlorophyll a/b ratio in chloroplasts isolated from young
illuminated leaves showed susceptibility to color. Color of illumination affects
the LHCII chiral macroaggregates in intact leaves and isolated chloroplasts,
providing light-induced alteration of the handedness of the LHCII chiral
macroaggregate, as measured with circular dichroism and circularly polarized
luminescence. The susceptibility of handedness to current illumination (red light
excitation of chlorophyll fluorescence) is dependent on the color under which the
plants were grown, and was maximal for the red-enriched illumination. We propose
the existence of a long-term (growth period) color memory, which influences the
susceptibility of the handedness of LHCII chiral macroaggregates to current
light.
PMID- 17029973
TI - The Judith Hoyer Lecture: genes, pixels, patterns, and prevention.
PMID- 17029974
TI - Driving prevalence and factors associated with driving among patients with
epilepsy.
AB - PURPOSE: The goal of the work described here was to determine the prevalence of
driving and associated variables among patients followed at a level 4 epilepsy
center. METHOD: A survey was mailed out to patients seen at the University of
Florida/Jacksonville Comprehensive Epilepsy Program. RESULTS: The study
population comprised 308 respondents. Nearly 20% of patients with poorly
controlled seizures continued to drive. Although several demographic and clinical
variables were associated with driving, on univariate analysis, using multiple
logistic regression, being employed, not receiving disability benefits, having
less frequent seizures, and taking fewer antiepileptic drugs were the variables
independently associated with driving. A subset analysis of patients with poorly
controlled seizures indicated that being employed was still an independent factor
associated with driving, along with higher annual household income and absence of
convulsions and waking seizures. CONCLUSION: A significant number of patients
with poorly controlled seizures drive. Being employed is a major reason these
patients continue to drive.
PMID- 17029975
TI - A multicenter, randomized, double-blind, placebo-controlled trial of long-term
ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL): the
study protocol [EudraCT no.: 2006-000032-27].
AB - There is no treatment for Charcot-Marie-Tooth disease 1A (CMT1A), but ascorbic
acid (AA) is efficacious in the transgenic mouse model. Thus, a clinical trial of
AA in CMT1A is warranted. The CMT-TRIAAL is a phase III randomized, double-blind,
placebo-controlled study involving 222 CMT1A adults from eight Italian centers.
Eligible for the study are symptomatic adults with genetically confirmed CMT1A.
Treatment consists of 2-year oral AA (1500mg/day) or placebo. The primary trial
endpoint is an improvement in CMT Neuropathy Score. Secondary efficacy endpoints
are changes in distal arm and leg maximum voluntary isometric contraction; 10m
timed walking; 9-hole-peg test; overall neuropathy limitations scale; pain and
fatigue visual analog scales; health-related quality of life (SF-36); and
electrophysiology. Clinical-electrophysiological assessments are performed at
baseline and every 6 months thereafter. In consenting patients from three
centers, skin biopsy is performed to evaluate PMP22 expression. The study will
last 34 months, starting from March 2006.
PMID- 17029976
TI - Mitochondrial processing of bovine adrenal steroidogenic acute regulatory
protein.
AB - Steroidogenic acute regulatory (StAR) protein is an important regulatory protein
in steroidogenesis and rapidly undergoes proteolysis after import into the
mitochondria. In this study, we determined the proteolytic cleavage sites and
investigated the effects on the stimulation of steroidogenic activity of the
blockage of these sites by mutation. The cleaved StAR proteins, which were
purified using an anti-StAR immobilized column, reacted with antiserum against
the StAR C-terminal oligopeptide. The molecular weights of the purified proteins
were determined by MALDI-TOF mass spectrometry, and were found to be identical to
those of the 40-285 and 55-285 amino-acid-regions of the StAR protein. To confirm
the identification of the cleavage sites, we constructed site-directed mutants of
bovine StAR cDNA, which contained the amino acids R37A/R38A/L40A and/or
R53A/R54A/R55A. These mutant StAR proteins expressed in COS-1 cells were not
cleaved at positions 39-40 and 54-55, and were processed at sites different from
those in the wild-type StAR protein. These mutant proteins stimulated
pregnenolone formation at almost the same rate as the wild-type StAR protein in
COS-1 cells, which suggests that the cholesterol transfer activity was not
affected by the mutation.
PMID- 17029977
TI - A constant-momentum/energy-selector time-of-flight mass spectrometer.
AB - A matrix assisted laser desorption/ionization time-of-flight mass spectrometer
has been built with an ion source that can be operated in either constant-energy
or constant-momentum acceleration modes. A decreasing electric field distribution
in the ion-accelerating region makes it possible to direct ions onto a space
focal plane in either modes of operation. Ions produced in the constant-momentum
mode have velocities and, thus, flight times that are linearly dependent on mass
and kinetic energies that are inversely dependent on mass. The linear mass
dispersion doubles mass resolving power of ions accelerated with space-focusing
conditions in constant-momentum mode. The mass-dependent kinetic energy is
exploited to disperse ions according to mass in a simple kinetic energy filter
constructed from two closely spaced, oblique ion reflectors. Focusing velocity of
ions of the same mass can substantially improve ion selection for subsequent post
source decay or tandem time-of-flight analyses.
PMID- 17029978
TI - Analysis of phenolic compounds in rhubarbs using liquid chromatography coupled
with electrospray ionization mass spectrometry.
AB - Rhubarb is an important herbal medicine for the treatment of constipation,
inflammation, and cancer. In this study, a facile method based on liquid
chromatography coupled with electrospray ionization tandem mass spectrometry has
been established for the analysis of bioactive phenolic compounds in rhubarbs.
From six rhubarb species, official (Rheum officinale, R. palmatum, and R.
tanguticum) and unofficial (R. franzenbachii, R. hotaoense, and R. emodi), a
total of 107 phenolic compounds were identified or tentatively characterized
based on their mass spectra. These compounds include sennosides, anthraquinones,
stilbenes, glucose gallates, naphthalenes, and catechins. Ion chromatograms for
the identified compounds of different rhubarbs were then compared. Consistent
with previous reports, sennosides and rhein were only detected in official
rhubarbs. Unexpectedly, we found that R. officinale contained very different
phenolic compounds from the other two official species. Sennoside A, which has
been considered as the major purgative component of rhubarb, was only detected in
R. officinale, while its close isomers were observed in R. palmatum and R.
tanguticum. In addition, the predominant anthraquinone glycosides in R.
officinale were found to be rhein 8-O-glucoside and emodin 1-O-glucoside, whereas
those in R. palmatum and R. tanguticum were rhein 1-O-glucoside and emodin 8-O
glucoside. Stilbenes, which are the major constituents of unofficial rhubarbs,
were also different among the species. Our results clarify the chemical
composition of rhubarbs comprehensively for the first time. Due to the
significant differences in chemical components of rhubarbs, we suggest that
different Rheum species be used separately in clinical practice.
PMID- 17029979
TI - A functional single nucleotide polymorphism in the vitamin-K-dependent gamma
glutamyl carboxylase gene (Arg325Gln) is associated with bone mineral density in
elderly Japanese women.
AB - The vitamin-K-dependent gamma-glutamyl carboxylase (GGCX) carboxylates vitamin-K
dependent proteins including bone Gla protein (osteocalcin) and matrix Gla
protein, which play important roles in bone metabolism. Therefore, GGCX
polymorphism might explain in part individual susceptibility to osteoporosis. In
the present study, polymorphisms in the exons of this gene were screened in
Japanese elderly women and a non-synonymous single nucleotide polymorphisms (SNP)
were found; c.8762 G>A; (Arg325Gln). When the kinetic parameters of GGCX325-Gln
and GGCX325-Arg were compared in vitro, Vmax/Km was significantly higher for
GGCX325-Gln (944.4+/-9.21 pmol/30 min/mg/mM FLEEL) than for GGCX325-Arg
(671.9+10.79 pmol/30 min/mg/mM FLEEL) (p=0.018). Then, association study of this
polymorphism with forearm bone mineral density (BMD) of Japanese postmenopausal
women (n=500, age 73.6+/-5.74) was conducted. As a result, the body mass index
(BMI)-adjusted Z score in the subpopulation older than 75 years (n=207) was
higher in those with 325-Gln (0.650+/-0.883, mean+/-SD) than those with 325
Arg/Gln or 325-Arg (0.133+/-0.650) (p=0.0383). This is the first report to
demonstrate the different activities of GGCX between the common genotypes and
their association with BMD.
PMID- 17029980
TI - Nuclear factor E2 p45-related factor 2 negatively regulates chondrogenesis.
AB - The transcription factor nuclear factor E2 p45-related factor 2 (Nrf2) forms
heterodimers with small musculoaponeurotic fibrosarcoma (Maf) proteins for the
selective recognition of the antioxidant responsive element on target genes,
followed by the regulation of gene expression of phase II detoxifying enzymes as
well as oxidative-stress-inducible proteins in different tissues. In the present
study, we investigated the role of Nrf2 in the regulation of chondrocyte
differentiation as well as the expression pattern of Nrf2 in cartilage. In tibia
from embryonic mice at E15.5, Nrf2 mRNA expression was restricted to both
proliferating and pre-hypertrophic chondrocytes, with few signals in early and
late hypertrophic chondrocytes expressing both type X collagen and osteopontin.
On in situ hybridization analysis of tibia from neonatal mice at 1 day after
birth, by contrast, Nrf2 was expressed in all chondrocytic layers in addition to
osteoblasts attached to cancellous bone. In pre-chondrogenic cell line ATDC5
cells, furthermore, expression of Nrf2 mRNA was also confirmed together with mRNA
expression of the Kelch-like ECH associating protein 1 and small Maf proteins. In
ATDC5 cells stably transfected with Nrf2, significant inhibition was seen in the
differentiation-dependent induction of alkaline phosphatase and increase in the
Alcian blue staining intensity. Furthermore, stable overexpression of Nrf2
significantly decreased mRNA expression of several chondrocyte differentiation
markers such as type II collagen, type X collagen and osteopontin. These data
suggest that Nrf2 may be a negative regulator of the cellular differentiation
toward maturation in chondrocytes.
PMID- 17029982
TI - Semaphorin 6C leads to GSK-3-dependent growth cone collapse and redistributes
after entorhino-hippocampal axotomy.
AB - We studied the changes in the distribution of a specific variant of Semaphorin
Y/6C (Sema6C) in mouse forebrain after axotomy of the entorhino-hippocampal
perforant pathway. We found this isoform to be widely expressed during
development, remaining in the adult and showing variations in distribution when
the perforant pathway was axotomized. These changes were detected in both the
hippocampal and entorhinal cortices. Sema6C1 immunoreactivity (IR) was high in
the stratum radiatum of the hippocampus proper and the inner molecular layer of
the dentate gyrus; the entorhinal cortex showed Sema6C1 IR in both cell bodies
and in fibers of the II/III and V/VI layers. In axotomized animals, the IR of the
ipsilateral, but not the contralateral, hemisphere showed that IR had moved into
the stratum lacunosum-moleculare, the medial molecular layer of the dentate gyrus
and the fibers, but not the cell bodies, of the entorhinal cortex. These results
were not reproduced after lateral axotomy of the fimbria fornix, indicating a
specific role for Sema6C variants in the generation and/or stability of entorhino
hippocampal synapses. Growth cone collapse of entorhinal and pyramidal neurons,
as well as activation of glycogen synthase kinase-3 (GSK-3) through depletion of
the inactive pool, induced by diffusible Sema6C1 further supports this view.
PMID- 17029981
TI - BDNF up-regulates alpha7 nicotinic acetylcholine receptor levels on
subpopulations of hippocampal interneurons.
AB - In the hippocampus, brain-derived neurotrophic factor (BDNF) regulates a number
of synaptic components. Among these are nicotinic acetylcholine receptors
containing alpha7 subunits (alpha7-nAChRs), which are interesting because of
their relative abundance in the hippocampus and their high relative calcium
permeability. We show here that BDNF elevates surface and intracellular pools of
alpha7-nAChRs on cultured hippocampal neurons and that glutamatergic activity is
both necessary and sufficient for the effect. Blocking transmission through NMDA
receptors with APV blocked the BDNF effect; increasing spontaneous excitatory
activity with the GABA(A) receptor antagonist bicuculline replicated the BDNF
effect. BDNF antibodies blocked the BDNF-mediated increase but not the
bicuculline one, consistent with enhanced glutamatergic activity acting
downstream from BDNF. Increased alpha7-nAChR clusters were most prominent on
interneuron subtypes known to directly innervate excitatory neurons. The results
suggest that BDNF, acting through glutamatergic transmission, can modulate
hippocampal output in part by controlling alpha7-nAChR levels.
PMID- 17029983
TI - Netrin1 exerts a chemorepulsive effect on migrating cerebellar interneurons in a
Dcc-independent way.
AB - Few studies have addressed the issue of how GABAergic interneurons in the
cerebellar cortex migrate or what guidance cues steer them. Recent data show that
their development starts at the cerebellar germinal epithelium on top of the
fourth ventricle. These interneurons continue to proliferate in the postnatal
cerebellar white matter and later migrate to their final position in the
cerebellar cortex. Here we report the chemorepulsive action of Netrin1 on
postnatal cerebellar interneurons in vitro and also show the expression pattern
of Netrin1 and its receptors Dcc and Unc5. Our expression results further suggest
that Netrin1 is involved in the migration of GABAergic interneurons in vivo.
Moreover, our data point to Bergmann glial fibers as possible tracks for these
cells en route to the molecular layer. Finally, experiments using blocking
antibodies allow us to conclude that Dcc, although expressed by postnatal
cerebellar interneurons, is not involved in the repulsive response triggered by
Netrin1 in these cells.
PMID- 17029984
TI - Cloning and overexpression of antifungal barley chitinase gene in Escherichia
coli.
AB - Plant chitinases are pathogenesis-related proteins, which are believed to be
involved in plant defense responses to pathogen infection. In this study,
chitinase gene from barley was cloned and overexpressed in Escherichia coli.
Chitinase (35 kDa) was isolated and purified. Since the protein was produced as
insoluble inclusion bodies, the protein was solubilized and refolded. Purified
chitinase exerted broad-spectrum antifungal activity against Botrytis cinerea
(blight of tobacco), Pestalotia theae (leaf spot of tea), Bipolaris oryzae (brown
spot of rice), Alternaria sp. (grain discoloration of rice), Curvularia lunata
(leaf spot of clover) and Rhizoctonia solani (sheath blight of rice). Due to the
potential of broad-spectrum antifungal activity barley chitinase gene can be used
to enhance fungal-resistance in crop plants such as rice, tobacco, tea and
clover.
PMID- 17029985
TI - Implementation and performance evaluation of reconstruction algorithms on
graphics processors.
AB - The high-throughput needs in electron tomography and in single particle analysis
have driven the parallel implementation of several reconstruction algorithms and
software packages on computing clusters. Here, we report on the implementation of
popular reconstruction algorithms as weighted backprojection, simultaneous
iterative reconstruction technique (SIRT) and simultaneous algebraic
reconstruction technique (SART) on common graphics processors (GPUs). The speed
gain achieved on the GPUs is in the order of sixty (60x) to eighty (80x) times,
compared to the performance of a single central processing unit (CPU), which is
comparable to the acceleration achieved on a medium-range computing cluster. This
acceleration of the reconstruction is caused by the highly specialized
architecture of the GPU. Further, we show that the quality of the reconstruction
on the GPU is comparable to the CPU. We present detailed flow-chart diagrams of
the implementation. The reconstruction software does not require special hardware
apart from the commercially available graphics cards and could be easily
integrated in software packages like SPIDER, XMIPP, TOM-Package and others.
PMID- 17029986
TI - Neural correlates of memory confidence.
AB - The present study aimed to shed light on the neural underpinnings of high vs. low
memory confidence. To dissociate memory confidence from accuracy, the Deese
Roediger McDermott (DRM) paradigm was employed, which - compared to other memory
paradigms - elicits a rather evenly distributed number of high-confident
responses across all possible combinations of memory response types (i.e., hits,
false alarms, correct rejections, and misses). In the standard DRM procedure,
subjects are first presented with thematically interrelated word lists at
encoding, which at recognition are intermixed with related and unrelated
distractor items. The signature of a false memory or DRM effect is an increased
number of high-confident false memories, particularly for strongly related lure
items. For the present study, 17 female subjects were administered a verbal DRM
task, whereas neural activation was indexed by fMRI. The behavioral analyses
confirmed the expected false memory effect: subjects made more high-confident old
responses (both hits and false alarms) the closer the items were related to the
central list theme. Across all four memory response types, an increase in
confidence at recognition was associated with bilateral activation in the
anterior and posterior cingulate cortex along with medial temporal regions. In
contrast, increments in doubt were solely related to activation in the superior
posterior parietal cortex. To conclude, the study provides some evidence for
dissociable systems for confidence and doubt.
PMID- 17029987
TI - Sources of systematic bias in hypercapnia-calibrated functional MRI estimation of
oxygen metabolism.
AB - The change in cerebral rate of oxidative metabolism (CMR(O(2))) during neural
activation may be estimated from blood oxygenation level-dependent (BOLD)
functional magnetic resonance imaging (fMRI) and arterial spin-labeling (ASL)
fMRI measurements. The established method relies on an epoch of iso-metabolic
blood flow increase, typically induced by CO2 breathing, to calibrate the BOLD
CBF relationship at resting-state CMR(O2). Here, we discuss the systematic bias
in CMR(O2)-CBF data that can be introduced depending on the value derived for the
calibration constant (M) from the CO2 breathing epoch. We demonstrate that the
fidelity of BOLD-CBF data acquired during the neural activation task have low
impact on the tightness of CMR(O2)-CBF coupling, as well as the coupling slope,
when the derived calibration value is of a relatively moderate amplitude (M in
the range of, or greater than, 10-15 at 1.5 T). Via the standard reformulation of
a grid in BOLD-CBF space into the CMR(O2)-CBF plane, we demonstrate the non
linear transformation that takes place and the sources of systematic bias that
result. We find that the outcome of a neurovascular coupling study may be
predicted to a large extent purely from the value of the calibration constant, M,
that is used. Our results suggest that the accurate determination of M is of
greater importance than thought previously and indicate that BOLD-CBF data must
always be supplied when considering CMR(O2)-CBF behavior in a particular brain
region.
PMID- 17029988
TI - Inverse retinotopy: inferring the visual content of images from brain activation
patterns.
AB - Traditional inference in neuroimaging consists in describing brain activations
elicited and modulated by different kinds of stimuli. Recently, however,
paradigms have been studied in which the converse operation is performed, thus
inferring behavioral or mental states associated with activation images. Here, we
use the well-known retinotopy of the visual cortex to infer the visual content of
real or imaginary scenes from the brain activation patterns that they elicit. We
present two decoding algorithms: an explicit technique, based on the current
knowledge of the retinotopic structure of the visual areas, and an implicit
technique, based on supervised classifiers. Both algorithms predicted the
stimulus identity with significant accuracy. Furthermore, we extend this
principle to mental imagery data: in five data sets, our algorithms could
reconstruct and predict with significant accuracy a pattern imagined by the
subjects.
PMID- 17029989
TI - Behavioral alterations in mice lacking the translation repressor 4E-BP2.
AB - The requirement for de novo protein synthesis during multiple forms of learning,
memory and behavior is well-established; however, we are only beginning to
uncover the regulatory mechanisms that govern this process. In order to determine
how translation initiation is regulated during neuroplasticity we engineered
mutant C57Bl/6J mice that lack the translation repressor eukaryotic initiation
factor 4E-binding protein 2 (4E-BP2) and have previously demonstrated that 4E-BP2
plays a critical role in hippocampus-dependent synaptic plasticity and memory.
Herein, we examined the 4E-BP2 knockout mice in a battery of paradigms to address
motor activity and motor skill learning, anxiety and social dominance behaviors,
working memory and conditioned taste aversion. We found that the 4E-BP2 knockout
mice demonstrated altered activity in the rotating rod test, light/dark
exploration test, spontaneous alternation T-maze and conditioned taste aversion
test. The information gained from these studies builds a solid foundation for
future studies on the specific role of 4E-BP2 in various types of behavior, and
for a broader, more detailed examination of the mechanisms of translational
control in the brain.
PMID- 17029990
TI - Granulocyte and granulocyte macrophage colony-stimulating factors as therapy in
human and veterinary medicine.
AB - Granulocyte colony-stimulating factors (G-CSFs) and granulocyte macrophage colony
stimulating factors (GM-CSFs) are endogenous cytokines that regulate granulocyte
colonies and play a major role in the stimulation of granulopoiesis (neutrophils,
basophils and eosinophils) and in the regulation of microbicidal functions. There
are numerous pathological conditions in which neutrophils are decreased, the most
common being neutropenia associated with cancer chemotherapy, which increases the
risk of serious microbial infections developing with the potential for high
morbidity and mortality. New methods in molecular biology have led to the
identification and cloning of CSF genes and biopharmaceutical production. Since
then, CSFs have been widely used for the prevention and treatment of neutropenia
associated with cancer chemotherapy, for mobilising haematopoietic cell
precursors, and for other neutropenia-related pathologies. This review focuses on
the use of CSFs within both human and veterinary medicine. Clinical applications,
pharmacology, tolerability and the potential role of these factors in veterinary
medicine are considered.
PMID- 17029991
TI - Paediatric and adult ataxias (update 5).
PMID- 17029992
TI - Current density imaging by pulsed conduction electron spin resonance.
AB - In analogy with Nuclear MRI, the ESR signal phase shift of conduction electrons
moving in electrical currents along controlled magnetic field gradients can be
used to generate spatial electronic current density maps. First two-dimensional
images of the current density distribution in quasi-one-dimensional organic
conductors are presented.
PMID- 17029993
TI - In vitro estimates of power output by epaxial muscle during feeding in largemouth
bass.
AB - Recent work has employed video and sonometric analysis combined with hydrodynamic
modeling to estimate power output by the feeding musculature of largemouth bass
in feeding trials. The result was an estimate of approximately 69 W kg(-1) of
power by the epaxial muscle during maximal feeding strikes. The present study
employed in vitro measurements of force, work and power output by fast-twitch
epaxial muscle bundles stimulated under activation conditions measured in vivo to
evaluate the power output results of the feeding experiments. Isolated muscle
bundles from the epaxial muscle, the sternohyoideus and the lateral red or slow
twitch muscle were tied into a muscle mechanics apparatus, and contractile
properties during tetanic contractions and maximum shortening velocity (Vmax)
were determined. For the epaxial muscles, work and power output during feeding
events was determined by employing mean stimulation conditions derived from a
select set of maximal feeding trials: 17% muscle shortening at 3.6 muscle
lengths/s, with activation occurring 5 ms before the onset of shortening. Epaxial
and sternohyoideus muscle displayed similar contractile properties, and both were
considerably faster (Vmax approximately 11-13 ML s(-1)) than red muscle (Vmax
approximately 5 ML s(-1)). Epaxial muscle stimulated under in vivo activation
conditions generated approximately 60 W kg(-1) with a 17% strain and
approximately 86 W kg(-1) with a 12% strain. These values are close to those
estimated by hydrodynamic modeling. The short lag time (5 ms) between muscle
activation and muscle shortening is apparently a limiting parameter during
feeding strikes, with maximum power found at an offset of 15-20 ms. Further,
feeding strikes employing a faster shortening velocity generated significantly
higher power output. Power production during feeding strikes appears to be
limited by the need for fast onset of movement and the hydrodynamic resistance to
buccal expansion.
PMID- 17029994
TI - Egg components, egg size, and hatchling size in leatherback turtles.
AB - Relationships between egg size, egg components, and neonate size have been
investigated across a wide range of oviparous taxa. Differences in egg traits
among taxa reflect not only phylogenetic differences, but also interactions
between biotic (i.e., maternal resource allocation) and abiotic (i.e. nest
environment conditions) factors. We examined relationships between egg mass, egg
composition, and hatchling size in leatherback turtles (Dermochelys coriacea)
because of the unique egg and reproductive characteristics of this species and of
sea turtles in general. Albumen comprised 63.0%+/-2.8% (mean+/-S.D.) of egg mass
and explained most of the variation in egg mass, whereas yolk comprised only
33.0%+/-2.7%. Additionally, leatherback albumen dry mass was approximately 16% of
albumen wet mass. Whereas hatchling mass increased significantly with egg mass (n
= 218 clutches), hatchling mass increased by only approximately 2 g for each 10 g
increase in egg mass and was approximately 10-20 g greater than yolk mass. Taken
together, our results indicate that albumen might play a particularly significant
role in leatherback embryonic development, and that leatherback eggs are both
capable of water uptake from the nest substrate and also possess a large
reservoir of water in the albumen. Relationships between egg mass and egg
components, such as variation in egg mass being largely explained by variation in
albumen mass and egg mass containing a relatively high proportion of albumen
solids, are more similar to bird eggs than to eggs of other non-avian reptiles.
However, hatchling mass correlates more with yolk mass than with albumen mass,
unlike patterns observed in bird eggs of similar composition.
PMID- 17029995
TI - Extraction and protein component analysis of venom from the dissected venom
glands of Latrodectus tredecimguttatus.
AB - Black widow spiders (genus Latrodectus) have attracted increasing attention due
to frequently reported human injuries caused by them and the potential
applications of biologically active components in their venoms. Although a number
of studies have described the biological properties and structures of several
venomous proteins such as latrotoxins, a comprehensive analysis of protein
component of the venom from the spider is not available. We used combinative
proteomic strategies to assess the protein components of the crude venom
collected from Latrodectus tredecimguttatus by extracting the dissected venom
glands. The experiments demonstrated that the crude venom of L. tredecimguttatus
has a high abundance of acidic proteins with molecular masses greater than 15
kDa, and the content of proteins and peptides of below 15 kDa is low. 86 unique
proteins were identified, part of which were contaminations of cellular
components during the extraction, determined in comparison with venom obtained by
electrostimulation. Except for members of latrotoxin family that were commonly
considered as the primary toxic components of the venom, several other special
enzymes and proteins were detected such as protease, phosphatase, lysozyme,
inhibitory protein, and so on. These protein components, particularly the
proteases, were speculated to play important roles in the action of L.
tredecimguttatus venom.
PMID- 17029996
TI - Effects of growth hormone and/or testosterone on very low density lipoprotein
apolipoprotein B100 kinetics and plasma lipids in healthy elderly men: a
randomised controlled trial.
AB - OBJECTIVE: To assess the effects of low dose recombinant growth hormone (GH),
testosterone (T) and combined GH and T, on lipid profiles and very low density
lipoprotein apolipoprotein B (VLDL apoB) metabolism. DESIGN AND PATIENTS: Sixty
nine healthy elderly men (65-80 yr) were studied in a six month double-blind,
placebo-controlled trial. Participants were randomised to placebo GH and placebo
T (P), GH and placebo T (GH), T and placebo GH (T) or GH and T (GHT).
MEASUREMENTS: Plasma lipid profiles were assessed before treatment and at 6
months. VLDL apoB absolute secretion rate (ASR) and fractional catabolic rate
(FCR) were measured in a subset of 21 men: P (n=5); GH (n=5); T (n=6); GHT (n=5),
with an infusion of 1-(13)C leucine. Fat mass (FM) was measured by DEXA and intra
abdominal fat (IAF) by CT scan. RESULTS: IGF-I levels increased in the GH and GHT
(P<0.001) groups: testosterone increased in the T (P=0.029) and GHT (P=0.05)
groups. There was no change in total cholesterol, LDL-cholesterol, HDL
cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B or
lipoprotein(a) in the GH, GHT or T groups. In the subset of 21 men, IGF-I levels
increased similarly with GH and GHT (P<0.01) but T levels increased only with T
(P<0.03). FM and IAF decreased significantly only with GHT (P<0.01, P=0.01).
Treatment with GH, T or GHT had no effect on VLDL apoB ASR or VLDL FCR.
CONCLUSION: Co-administration of GH and T in near physiological doses in healthy
elderly men resulted in favourable changes in body composition without altering
the plasma lipid profile or VLDL apoB metabolism.
PMID- 17029997
TI - A failure of resilience: estimating response of New York City's public health
ecosystem to sudden disaster.
AB - Adapting methodology from resilience theory in ecology, we develop an empirical
model of the response of the New York City public health ecosystem to sudden
disaster. Contrary to cultural expectation, 'good' and 'bad' neighborhoods
starkly differentiated by public health status reflecting longstanding economic
and racial segregation-respond similarly to challenge. This suggests that the
difference in health between neighborhoods is primarily predicated on the extent
to which they have been, and continue to be, exposed to differing patterns of
stressors and affordances, rather than to any difference in underlying socio
economic vulnerability. Paradoxically, then, these urban neighborhoods constitute
a single, highly interdependent, health ecosystem, despite substantial
socioeconomic and racial segregation.
PMID- 17029998
TI - VISA--a pass to innate immunity.
AB - Virus-induced signaling adaptor (VISA) is essential for host innate immune
responses against double-stranded RNA viral infection and viral replication. It
is an adaptor that activates the transcription factors nuclear factor kappaB (NF
kappaB) and interferon regulatory factor 3 (IRF3) that regulate the expression of
type I interferons. The localization of VISA to the outer membrane of
mitochondria and the cellular consequences of its activation implicate this
protein in the cellular etiology of neurodegenerative disorders.
PMID- 17029999
TI - Streptococcus pyogenes: Insight into the function of the streptococcal
superantigens.
AB - The group A streptococcus produces a number of highly potent exoproteins that act
as superantigens. The cascade of pro-inflammatory events that follow invasive
streptococcal infection is greatly enhanced by production of such toxins, leading
to profound hypotension and multi-organ failure in some cases. Superantigens such
as streptococcal mitogenic exotoxin Z (SMEZ) interact with host MHC class II and
the T cell receptor, leading to activation events in both cells. In vitro, these
interactions lead to expansion and cytokine production by specified T cell
subsets. Studies using humanized HLA class II transgenic mice and isogenic
streptococcal strains have characterised the in vivo responses to superantigens
produced in the context of live infection. Notwithstanding the obvious
deleterious role of superantigens in toxic shock, the evolutionary advantage
conferred by these toxins remains a subject of speculation.
PMID- 17030000
TI - An in vitro method for selective detection of free monomeric ubiquitin by using a
C-terminally biotinylated form of ubiquitin.
AB - In an effort to design a selective assay allowing detection of free monomeric
ubiquitin, an approach based on a C-terminally biotinylated form of ubiquitin is
proposed. In the form of a polyubiquitin chain, ubiquitin marks proteins for
degradation by the 26S proteasome. This covalently attached signal is assembled
from multiple ubiquitins linked to each other via the C-terminus of one ubiquitin
and the epsilon-amine of Lys48 of another ubiquitin. In the present study, a form
of ubiquitin having the C-terminus modified with the addition of a biotinylation
peptide tag was prepared. After expression, this modified ubiquitin was
biotinylated in vitro using recombinant biotin ligase. Biotinylated ubiquitin was
further purified using affinity chromatography on immobilized monovalent avidin.
This tagged form of ubiquitin is blocked at the C-terminus and therefore can only
act as an acceptor (Lys-48 donor) in polyubiquitin chain synthesis. In vitro
enzymatic assembly of multiubiquitin chains from biotinylated monoubiquitin and
natural monoubiquitin is demonstrated by Western blot analysis using horseradish
peroxidase-conjugated streptavidin. Data obtained with this assay indicate
potential uses of the C-terminally biotinylated form of ubiquitin for selective
detection of monoubiquitin contamination in a cell extract experimentally
depleted of ubiquitin, i.e. lysate Fraction II. Cell-free systems established for
in vitro examination of ubiquitin involvement in proteolytic processes usually
employ Fraction II, which should be essentially ubiquitin-free. It is suggested
that the assay using biotinylated monoubiquitin can be useful to exclude the
possibility that ubiquitin contamination of laboratory prepared lysate Fraction
II accounts for protein degradation in this fraction.
PMID- 17030001
TI - Effects of the single point genetic mutation D54G on muscle creatine kinase
activity, structure and stability.
AB - Aberrant folding of important proteins caused by genetic mutations is closely
correlated to many diseases. Due to the important physiological role in excitable
cells, the activity and level of creatine kinase (CK) play a crucial role in
maintaining body functions. Muscle CK deficiency disease was identified by an
unusual CK activity decrease in an acute myocardial infarction patient caused by
the single point mutation D54G. In this research, it was found that the D54G
mutant had substantially decreased activity, substrate binding affinity and
stability. Spectroscopic experiments indicated that the mutation impaired the
structure of CK, which resulted in a partially unfolded state with more
hydrophobic exposure and exposed Trp residues. The inability to fold to the
functional compact state made the mutant be prone to aggregate upon
microenvironmental stresses, and might gradually decrease the CK level of the
patient.
PMID- 17030002
TI - Interleukin-22: a novel T- and NK-cell derived cytokine that regulates the
biology of tissue cells.
AB - Interleukin (IL)-22, discovered in 2000, is a member of the IL-10 family of
cytokines. The major sources of IL-22 are activated T1- and NK-cells. IL-22 acts
via a heterodimeric receptor complex consisting of IL-22R1 and IL-10R2. Neither
resting nor activated immune cells express IL-22R1 or respond to IL-22. In
contrast, tissue cells at outer body barriers, i.e. of the skin, kidney, and the
digestive and respiratory systems are targets of this cytokine. IL-22 functions
by promoting the anti-microbial defense, protecting against damage, and re
organizing non-immune tissues. Furthermore, IL-22 induces acute phase reactants.
These findings indicate that IL-22 represents a novel type of immune mediator
that, although produced by immune cells, regulates tissue protection and
homeostasis.
PMID- 17030003
TI - Peptide-based fibrous biomaterials: Some things old, new and borrowed.
AB - Bioinspired fibrous materials that span the nano-to-meso scales have potentially
broad applications in nanobiotechnology; for instance, as scaffolds in 3D cell
culture and tissue engineering, and as templates for the assembly of other
polymer and inorganic materials. The field is burgeoning, and this review is
necessarily focused. It centres on recent developments in the design of peptide
based fibres and particularly those using the alpha-helix and the collagen triple
helix as building blocks for self-assembly. Advances include new designs in both
categories, the assembly of more-complex topologies using fibres themselves as
building blocks, and the decoration of the assembled materials with functional
moieties.
PMID- 17030005
TI - Nature of water in nacre: a 2D Fourier transform infrared spectroscopic study.
AB - In this work, the interactions of aragonite and organic matrix in nacre with
water are investigated using two-dimensional (2D) Fourier transform infrared
(FTIR) spectroscopy. The 2D-FTIR analysis revealed four bands in the OH
stretching region at around 3550, 3445, 3272 and 3074 cm(-1). Two additional
bands were found at around 3616 and 3282 cm(-1) after deconvolution of the nacre
spectrum. The bands at around 3616 and 3550 cm(-1) are assigned to asymmetric and
symmetric OH stretching of partially hydrogen bonded water molecules. The bands
at around 3445 and 3272 cm(-1) are assigned to asymmetric and symmetric OH
stretching of water molecules fully hydrogen bonded with surrounding water
molecules. Presence of above bands in the nacre spectrum suggests that water, in
form of clusters, is present in protein matrix and aragonite pores. Water may
also hydrogen bond with the organic matrix. The bands observed at 3282 and 3074
cm(-1) are assigned to asymmetric and symmetric OH stretching of water molecules,
chemisorbed on surfaces of aragonite platelets. Polarization experiments suggest
that H-O-H plane of water molecules is along to c-axis of aragonite platelets.
PMID- 17030006
TI - Development of an optode membrane for high pH values.
AB - The development of an optical pH sensor for high pH values is described based on
the immobilization of Aniline Blue on an optically transparent triacetylcellulose
membrane. The membrane is useful for repetitive and reversible pH measurements in
the pH range of 8.8-13. The relative standard deviation is about 1.6% and 2% for
seven measurements of the maximum change at 579 nm from pH 9 to 10.8 and from pH
11.1 to 12.8, respectively. Other advantages of the sensor include rapid
equilibration time, long term stability, reversibility, high sensitivity, freedom
from interference of other cations and ease of fabrication.
PMID- 17030007
TI - Theoretical studies on electrochemistry of p-aminophenol.
AB - Geometric parameters, vibrational frequencies and thermochemical values of p
quinonimine (p-Q) and p-aminophenol (p-AP) were computed by ab initio calculation
(HF) and density function theory (DFT) with the 6-31G(d,p) basis set. Cyclic
voltammetry with a goldren electrode of p-AP solutions in phosphate buffers at pH
7.30 showed that standard electrode potential of half reaction for (p-Q) and (p
AP) is 0.728V. Standard electrode potential of half reaction for p-Q and p-AP
were calculated using the sum of electronic and thermal free energies of p-Q and
p-AP with normal hydrogen electrode (NHE) as a reference electrode. The results
show that the theoretical standard electrode potential of half reaction for p-Q
and p-AP is 0.682V at B3LYP/6-31G(d,p) level and 0.622V at HF/6-31G(d,p) level,
respectively, indicating that computed standard electrode potential at B3LYP/6
31G(d,p) level are more reliable than that at HF/6-31G(d,p) level.
PMID- 17030008
TI - Mass spectrometric investigation of buspirone drug in comparison with thermal
analyses and MO-calculations.
AB - The buspirone drug is usually present as hydrochloride form of general formula
C(21)H(31)N(5)O(2).HCl, and of molecular weight (MW)=421.96. It is an analgesic
anxiolytic drug, which does not cause sedative or depression of central nervous
system. In the present work it is investigated using electron impact mass
spectral (EI-MS) fragmentation at 70 eV, in comparison with thermal analyses (TA)
measurements (TG/DTG and DTA) and molecular orbital calculation (MOC). Semi
empirical MO calculation, PM3 procedure, has been carried out on buspirone both
as neutral molecule (in TA) and the corresponding positively charged species (in
MS). The calculated MOC parameters include bond length, bond order, particle
charge distribution on different atoms and heats of formation. The fragmentation
pathways of buspirone in EI-MS lead to the formation of important primary and
secondary fragment ions. The mechanism of formation of some important daughter
ions can be illuminated from comparing with that obtained using electrospray
ESIMS/MS mode mass spectrometer through the accurate mass measurement
determination. The losses of the intermediate aliphatic part (CH2)4 due to
cleavage of N-C bond from both sides is the primary cleavage in both techniques
(MS and TA). The PM3 provides a base for fine distinction among sites of initial
bond cleavage and subsequent fragmentation of drug molecule in both TA and MS
techniques; consequently the choice of the correct pathway of such fragmentation
knowing this structural session of bonds can be used to decide the active sites
of this drug responsible for its chemical, biological and medical reactivity.
PMID- 17030009
TI - Structure elucidation of laser dye coumarin-540A by joint application of X-ray
diffraction, X-ray fluorescence, prompt fluorescence, UV and visible
spectroscopy.
AB - X-ray, ultraviolet, and visible light induced photophysical changes of coumarin
540A in ethanol have been studied by the joint applications of X-ray,
ultraviolet, and visible spectroscopy. Some impurities were found by X-ray
fluorescence measurements. During the high power optical pumping, coumarin showed
photochemical changes. Photoproduct emission spectra characteristics showed that
photoproduct molecules can also be used as a laser dye at a different emission
frequency in the ultraviolet region.
PMID- 17030011
TI - Global transcriptional effects of PEG-IFN-alpha and ribavirin on peripheral blood
cells obtained from patients with chronic hepatitis C.
AB - The global transcriptional profile during the first 4 weeks of treatment with
pegylated interferon alfa (PEG-IFN-alpha) therapy for chronic hepatitis C (CHC)
was evaluated. cDNA array technology was used to assess expression of 10,918
human genes in peripheral blood cells obtained from 17 CHC patients at days 0, 7,
and 28 following treatment with PEG-IFN-alpha and ribavirin. Hierarchical average
linkage clustering identified seven temporal profiles of differential expression
comprising 148 genes. Gene expression profiles were comparable between the PEG
IFN-alpha-2a and PEG-IFN-alpha-2b therapy. Genes representing a broad range of
molecular functions were differentially regulated with distinct temporal patterns
of expression. The initial global response to interferon treatment appears to be
a net up-regulation of genes, consistent with gene responses identified
previously in vitro, though by 4 weeks an overall down-regulation of genes was
observed. Novel transcription factors potentially involved in secondary gene
regulation cascades, a potential dsRNA receptor and members of the ubiquitin
signaling, including a novel predicted deubiquitinating peptidase were all
identified as being up-regulated upon treatment with IFN. The overall findings
provide new light on possible physiological effects of IFN-alpha and open new
lines of investigations on the mode of action of PEG-IFN-alpha combination
therapy.
PMID- 17030010
TI - Optical characterization of Sm3+ and Dy3+:ZnO-PbO-B2O3 glasses.
AB - Here, we present the results of the analysis of Sm(3+) or Dy(3+) (0.5 mol%) ions
doped heavy metal oxide (HMO)-based zinc lead borate (ZLB) glasses. Optical
measurements such as absorption, emission spectra, lifetimes, XRD, DSC profiles
have been carried out. The emission spectrum of Sm(3+):ZLB has shown the emission
transitions of (4)G(5/2)-->(6)H(5/2) (563 nm), (4)G(5/2)-->(6)H(7/2) (598 nm),
(4)G(5/2)-->(6)H(9/2) (646 nm), (4)G(5/2)-->(6)H(11/2) (708 nm) with lambda(exc):
401 nm ((6)H(5/2)-->(4)F(7/2)). In the case of the Dy(3+):ZLB glass, emission
transitions of (4)F(9/2)-->(6)H(15/2) (485 nm), (4)F(9/2)-->(6)H(13/2) (575 nm)
and (4)F(9/2)-->(6)H(11/2) (664 nm) with lambda(exi): 447 nm ((6)H(15/2)-
>(4)I(15/2)) have been identified. Energy level schemes relating to the emission
mechanisms involved in Sm(3+) and Dy(3+) glasses have been given.
PMID- 17030012
TI - The t-CWT: a new ERP detection and quantification method based on the continuous
wavelet transform and Student's t-statistics.
AB - OBJECTIVE: This study was aimed at developing a method for extraction and
assessment of event-related brain potentials (ERP) from single-trials. This
method should be applicable in the assessment of single persons' ERPs and should
be able to handle both single ERP components and whole waveforms. METHODS: We
adopted a recently developed ERP feature extraction method, the t-CWT, for the
purposes of hypothesis testing in the statistical assessment of ERPs. The t-CWT
is based on the continuous wavelet transform (CWT) and Student's t-statistics.
The method was tested in two ERP paradigms, oddball and semantic priming, by
assessing individual-participant data on a single-trial basis, and testing the
significance of selected ERP components, P300 and N400, as well as of whole ERP
waveforms. The t-CWT was also compared to other univariate and multivariate ERP
assessment methods: peak picking, area computation, discrete wavelet transform
(DWT) and principal component analysis (PCA). RESULTS: The t-CWT produced better
results than all of the other assessment methods it was compared with.
CONCLUSIONS: The t-CWT can be used as a reliable and powerful method for ERP
component detection and testing of statistical hypotheses concerning both single
ERP components and whole waveforms extracted from either single persons' or group
data. SIGNIFICANCE: The t-CWT is the first such method based explicitly on the
criteria of maximal statistical difference between two average ERPs in the time
frequency domain and is particularly suitable for ERP assessment of individual
data (e.g. in clinical settings), but also for the investigation of small and/or
novel ERP effects from group data.
PMID- 17030013
TI - Seizures and adverse events during routine scalp electroencephalography: a
clinical and EEG analysis of 1000 records.
AB - OBJECTIVE: To quantify the incidence of seizures and adverse events during
standard electroencephalography (EEG). METHODS: A retrospective random sample of
1000 of a total of 3391 reports of standard scalp EEG recordings during 2002 at
Kings College Hospital were studied, and adverse events during standard EEG were
recorded. Photic induced seizures and epileptiform activity were compared with
the resting, hyperventilation and sleep EEG. RESULTS: Adverse events occurred in
131 records (13.1%), including seizures in 60 records (45 electro-clinical and 15
non-epileptic seizures). The overall incidence of electro-clinical seizures was
not statistically different during the resting EEG (2.8%), sleep EEG (2%),
hyperventilation EEG (2.1%) and during photic stimulation EEG (1.4%). There was a
higher frequency of electro-clinical seizures during hyperventilation and sleep
in those with a diagnosis of idiopathic generalised epilepsy (31.5%) and during
photic stimulation in photosensitive patients (31%). The incidence of electro
clinical seizures was significantly less during activation procedures in focal
epilepsies (2.6%). Activation techniques made a unique diagnostic contribution
when routine resting EEG was normal or equivocal in 11% of cases. CONCLUSIONS:
Adverse events occurred in 13.1% of records, and most were minor. Sixty of the
adverse events were seizures. Those generated during the EEG were brief and
safety precautions operated successfully. In those without a prior diagnosis, the
chance of seizures is the same during both resting and activation EEG. In those
patients with generalised epilepsy or photosensitivity, activation procedures
have a higher rate of seizure induction. SIGNIFICANCE: This study has
implications for informed consent for EEG.
PMID- 17030014
TI - A high prevalence of sleep disordered breathing in men with mild symptomatic
chronic heart failure due to left ventricular systolic dysfunction.
AB - BACKGROUND: Sleep disordered breathing (SDB) is common in severe chronic heart
failure (CHF) and is associated with increased morbidity and mortality. The
prevalence of SDB in mild symptomatic CHF is unknown. AIM: The aim of this study
was to determine the prevalence and characteristics of SDB in male patients with
NYHA class II symptoms of CHF. METHODS AND RESULTS: 55 male patients with mild
symptomatic CHF underwent assessment of quality of life, echocardiography,
cardiopulmonary exercise, chemoreflex testing and polysomnography. 53% of the
patients had SDB. 38% had central sleep apnoea (CSA) and 15% had obstructive
sleep apnoea. SDB patients had steeper VE/VCO(2) slope [median (inter-quartile
range) 31.1 (28-37) vs. 28.1 (27-30) respectively; p=0.04], enhanced
chemoreflexes to carbon dioxide during wakefulness [mean+/-sd: 2.4+/-1.6 vs.
1.5+/-0.7 %VE Max/mmHg CO(2) respectively; p=0.03], and significantly higher
levels of brain natriuretic peptide and endothelin-1 compared to patients without
SDB. No differences in left ventricular ejection fraction, percent predicted peak
oxygen uptake, or symptoms of SDB were observed. CONCLUSIONS: A high prevalence
of SDB was found in men with mild symptomatic CHF. Patients with SDB could not be
differentiated by symptoms or by routine cardiac assessment making clinical
diagnosis of SDB in CHF difficult.
PMID- 17030015
TI - Involvement of insulin-like growth factor-I in the control of glucose
homeostasis.
AB - Insulin-like growth factor-I (IGF-I) has significant structural homology with
proinsulin. IGF-I binds to insulin receptors, stimulates insulin-like actions and
enhances insulin sensitivity. However, because circulating IGF-I is bound to high
affinity binding proteins and has relatively low affinity for insulin receptors,
most of its ability to alter insulin sensitivity is mediated indirectly (i.e.
through suppression of growth hormone, a known insulin antagonist). Direct
effects of IGF-I on insulin actions are tissue specific, occurring principally in
skeletal muscle and kidney. Genetic manipulations in experimental mouse models
have been used to analyze the role of endogenous IGF-I on insulin action. These
studies have shown that suppression of growth hormone is important for enhancing
insulin action in the liver and that deletion of the IGF-I receptor in skeletal
muscle results in severe insulin resistance. IGF-I also suppresses renal
gluconeogenesis, which might contribute to its glucose-lowering actions. In
humans, IGF-I enhances insulin sensitivity and lowers blood glucose in patients
with either extreme insulin resistance or type 2 diabetes. It also decreases
insulin requirement in patients with insulin-deficient diabetes. Taken together,
these findings suggest that IGF-I is functioning coordinately with insulin to
regulate glucose homeostasis.
PMID- 17030017
TI - Transmission control for schistosomiasis - why it matters now.
AB - Current population-based schistosomiasis treatment programs are a first step to
reducing the global burden of Schistosoma-related disease; however, they might
not dramatically reduce parasite transmission in highly endemic areas.
Consequently, the benefits of these programs remain in doubt because recurring
low-level reinfection is likely to be associated with subtle but persistent
morbidities such as anemia, undernutrition and diminished performance status. The
real health benefits of transmission control need to be reconsidered and
attention given to more aggressive and, ultimately, more affordable parasite
elimination strategies. The next generation of schistosomiasis control can be
optimized using new monitoring tools and effective transmission containment.
PMID- 17030018
TI - B-cell immune responses in HIV positive and HIV negative patients with
tuberculosis evaluated with an ELISA using a glycolipid antigen.
AB - The diagnostic value of the PGL-Tb1 enzyme-linked immunosorbent assays (ELISA)
was established following a survey study using sera from 220 Tuberculosis
patients (including 69 HIV coinfected) and 324 controls. A higher percentage
(76.8%) of the HIV-seropositive compared to the HIV-seronegative (58.9%) TB
patients were ELISA positive (p=0.02) with a specificity of 94%. In HIV-positive
TB patients, ELISA sensitivity was identical for all sites of disease and
antibody levels were not affected by the CD4+ counts, PPD results, age or
bacterial yield. Combining data for both the smear microscopy and ELISA maximized
sensitivity. The kinetics of anti-PGL-Tb1 antibody was evaluated in cohort
studies using sera collected before, during and after treatment for clinical TB
for 79 TB patients (including 39 HIV coinfected). Statistically significant ELISA
signals were observed in 51.3% of HIV-seropositive TB patients prior to the
diagnosis of clinical TB and elevated antibody levels persisting 18 months after
the end of antituberculous chemotherapy. Asymptomatic development of antibody
also occurred in 22.7% of a cohort of 44 HIV-positive patients with a high risk
of tuberculosis, but no correlation was found between persisting elevated
antibody levels and progression to active disease. This antibody response in
absence of disease, might reflect the control of an incipient tuberculosis
infection by antituberculous prophylaxis or through an improved protective immune
response associated with antiretroviral therapy.
PMID- 17030019
TI - Long-chain multiple methyl-branched fatty acid-containing lipids of Mycobacterium
tuberculosis: biosynthesis, transport, regulation and biological activities.
AB - The cell envelope of pathogenic mycobacteria is highly distinctive in that it
contains a number of lipids esterified with structurally related long-chain multi
methyl-branched fatty acids. These lipids have long been thought to play
important roles in the cell envelope structure as well as in the pathogenicity of
the tubercle bacillus. This review summarizes what is known about the
biosynthesis of long-chain multiple methyl-branched fatty acid-containing lipids
in Mycobacterium tuberculosis and describes the most recent findings about their
regulation, transport across the different layers of the cell envelope and their
biological functions.
PMID- 17030021
TI - Application of tissue Doppler to interpretation of exercise echocardiography:
diagnostics of ischemia localization in patients with ischemic heart disease.
AB - Development of optimal methods for the objective non-invasive diagnosis of
coronary artery disease remains a challenge for imaging techniques in stress
tests. AIM: The aim of this study was to obtain quantitative diagnostic criteria
TDI which could detect significant coronary artery disease during exercise
echocardiography. METHODS AND RESULTS: We evaluated regional systolic and
diastolic myocardial functions of 123 patients by pulsed wave tissue Doppler
imaging (TDI) in eight segments of left ventricle during exercise stress testing.
Diagnostic criteria were obtained by comparing TDI and coronary angiography data.
Best cut-points of velocity parameters allowed developing two diagnostic models
for the detection of left anterior descending (LAD) and circumflex (LCx) artery
diseases. The accuracy of the TDI diagnostic model for LAD-disease was 86.2% and
for LCx-disease 78.3%. There were no criteria for the detection of RCA disease in
this study. CONCLUSION: So TDI is a very accurate method for the detection of LAD
and LCx-disease during exercise stress echocardiography.
PMID- 17030020
TI - Cardiac hemangioma of the right atrium.
AB - Primary cardiac tumors are rare, with an incidence range between 0.001% and
0.030% at autopsy. Recent technical advances have facilitated diagnosis and
surgical treatment of such lesions. Patients with a resectable tumor usually have
a good prognosis, but patients with an unresectable tumor may have a poor
prognosis. This report shows a case of right atrial hemangioma growing like an
extracardiac mass, with cardiac tamponade the only clinical presentation.
PMID- 17030022
TI - Spontaneous chordae rupture of tricuspid valve in patient with chronic renal
failure.
AB - Spontaneous chordae rupture of the tricuspid valve is relatively rare, unlike the
mitral valve. We present a 27-year-old male with chronic renal failure on
hemodialysis therapy for treatment of parathyroid adenoma. The echocardiography
showed the severe tricuspid regurgitation with chordae rupture which was not
noted 1 year ago. In addition, the papillary muscle of both mitral and tricuspid
valve was shortened and calcified extensively. However, in his clinical history,
the specific causes for chordae rupture, such as chest trauma or endocarditis,
were not disclosed. It was presumed that dilated right ventricle with volume or
pressure overloading and secondary hyperparathyroidism are probably responsible
for the chordae rupture of tricuspid valve.
PMID- 17030023
TI - Echocardiographic evaluation of mitral tethering for 'chordal cutting' procedure.
AB - 'Chordal cutting' is a recently proposed surgical option for the treatment of
functional mitral regurgitation due to leaflet tethering. With this technique the
surgeon sections second order chordae, restores leaflet's convexity towards the
left atrium and eliminates mitral incompetence. Preoperative assessment of
tethering mechanism, degree of leaflet distortion, surface of coaptation, annular
dilation, origin and quantification of valve incompetence by echocardiographic
means is essential in indicating this surgical option. Intraoperative
transesophageal evaluation is crucial to assess the morphology and the absence or
degree of residual incompetence after procedure.
PMID- 17030024
TI - Daily rhythms of seizure activity and behavior in a model of atypical absence
epilepsy.
AB - We studied daily rhythms of chronic seizure activity and behavior in adult rats
and mice treated with the cholesterol biosynthesis inhibitor AY-9944 (AY) during
early postnatal development. Chronic atypical absence seizures were verified in
the AY-treated animals by the presence of spontaneous 5- to 6-Hz slow spike-wave
discharges (SSWDs) in the neocortex. General behavioral activity, as measured by
total movements (TM), movement time (MT), ambulatory movement time (AMT), time
spent in center of arena (CT), jumps (JFP), and rotational behavior (TURNS), were
continuously recorded under a 12-hour light:12-hour dark photocycle. The average
SSWD duration in AY-treated rats varied daily, with two peaks occurring at
approximately dark phase and light phase onset. Mice treated with AY exhibited
significant increases in all behavioral measures during the light and dark
phases, with the exception of light-phase CT, which did not differ from that of
controls. Consequently, the daily rhythm of total behavioral activity (TM)
exhibited a significantly higher mean oscillation (mesor) and amplitude without
evidence of phase shift compared with the TM rhythm of controls. The occurrence
of SSWD activity in the AY model appears to be subject to regulation by
biological timing mechanisms and, furthermore, associated with motor
hyperactivity that does not alter the timing of behavioral rhythmicity.
PMID- 17030026
TI - Proteomic inventory of "anchorless" proteins on the colon adenocarcinoma cell
surface.
AB - Surface proteins play important pathophysiological roles in health and disease,
and accumulating proteomics-based studies suggest that several "non-membrane"
proteins are sorted to the cell surface by unconventional mechanisms.
Importantly, these proteins may comprise attractive therapeutic targets and novel
disease markers for colon cancer. To perform a proteomics-based inventory of
these so-called "anchorless" surface proteins, intact colon adenocarcinoma SW480
cells were labeled with membrane-impermeable biotin after which only soluble
biotinylated proteins were isolated and identified by nanoLC-MS/MS. Computer
assisted analysis predicted that only 9 of the 97 identified surface-exposed
proteins have predicted secretory signal peptides, whereas 2 other proteins have
a putative transmembrane segment. Of the 9 proteins with putative signal
peptides, 1 was predicted to be retained at the cell surface by a GPI-anchor,
whereas 5 other proteins contained an ER-retention motif (KDEL) that should
prevent them from being sorted to the cell surface. The remaining 86 soluble
"surface" proteins lack known export signals and the possibility that these
proteins are candidate substrates of non-classical transporters or exported by
unconventional mechanisms is discussed. Alternatively, the large number of
"intracellular" and ER-resident proteins may imply that biotinylation approaches
are not only specific for surface proteins, but also biased against a certain
subset of non-surface proteins. This underscores the importance of post-proteomic
verification of proteomics-based inventories on surface-exposed proteins, which
eventually should reveal to which extent non-classical export and retention
mechanisms contribute to the sorting of "anchorless" proteins to the surface of
colon tumor cells.
PMID- 17030025
TI - A novel type of lysine oxidase: L-lysine-epsilon-oxidase.
AB - The melanogenic marine bacterium M. mediterranea synthesizes marinocine, a
protein with antibacterial activity. We cloned the gene coding for this protein
and named it lodA [P. Lucas-Elio, P. Hernandez, A. Sanchez-Amat, F. Solano,
Purification and partial characterization of marinocine, a new broad-spectrum
antibacterial protein produced by Marinomonas mediterranea. Biochim. Biophys.
Acta 1721 (2005) 193-203; P. Lucas-Elio, D. Gomez, F. Solano, A. Sanchez-Amat,
The antimicrobial activity of marinocine, synthesized by M. mediterranea, is due
to the hydrogen peroxide generated by its lysine oxidase activity. J. Bacteriol.
188 (2006) 2493-2501]. Now, we show that this protein is a new type of lysine
oxidase which catalyzes the oxidative deamination of free L-lysine into 6
semialdehyde 2-aminoadipic acid, ammonia and hydrogen peroxide. This new enzyme
is compared to other enzymes related to lysine transformation. Two different
groups have been used for comparison. Enzymes in the first group lead to 2
aminoadipic acid as a final product. The second one would be enzymes catalyzing
the oxidative deamination of lysine releasing H2O2, namely lysine-alpha-oxidase
(LalphaO) and lysyl oxidase (Lox). Kinetic properties, substrate specificity and
inhibition pattern show clear differences with all above mentioned lysine-related
enzymes. Thus, we propose to rename this enzyme lysine-epsilon-oxidase (lod for
the gene) instead of marinocine. Lod shows high stereospecificity for free L
lysine, it is inhibited by substrate analogues, such as cadaverine and 6
aminocaproic acid, and also by beta-aminopropionitrile, suggesting the existence
of a tyrosine-derived quinone cofactor at its active site.
PMID- 17030027
TI - Effects of reserpine on the plus-maze discriminative avoidance task: dissociation
between memory and motor impairments.
AB - We investigated the effects of reserpine (0.1-0.5 mg/kg) on the performance of
mice in the plus-maze discriminative avoidance task (DAVT), which simultaneously
evaluates memory and motor activity. All doses induced memory impairment
(increased aversive arm time) but only 0.5 mg/kg reserpine decreased locomotion
(entries in enclosed arms). The results suggest that the DAVT evaluation in
reserpine-treated mice can be a useful model for studying cognitive deficits
accompanied by motor impairments.
PMID- 17030028
TI - Functional imaging with laser speckle contrast analysis: vascular compartment
analysis and correlation with laser Doppler flowmetry and somatosensory evoked
potentials.
AB - Laser Speckle Contrast Analysis (LASCA), a novel, high-resolution blood flow
imaging method, was performed on rat somatosensory cortex during functional
activation. In the same animals, cerebral blood flow (CBF) was measured with
Laser Doppler Flowmetry. To obtain a quantitative estimate of the underlying
neuronal activity, somatosensory evoked potentials were recorded simultaneously
with an epidural EEG. Our results show that: 1. CBF changes measured by LASCA or
LDF are nonlinearly dependent on the magnitude of electrical neural activity
revealed by somatosensory evoked potentials. 2. The magnitude of relative CBF
changes measured by LASCA and LDF shows a strong correlation. 3. LASCA imaging
localizes the highest relative changes of CBF in microcirculatory areas, with a
smaller contribution by larger vessels. This study demonstrates that LASCA is a
reliable method that provides 2D-imaging of CBF changes that are comparable to
LDF measurements. It further suggests that functional neuroimaging methods based
on CBF enhance areas of microcirculation and thus might prove more accurate in
localizing neural activity than oxygenation related methods like BOLD-fMRI.
PMID- 17030030
TI - Cannabinoid CB1 receptor antagonism modulates plasma corticosterone in rodents.
AB - Although the involvement of cannabinoids and the endogenous cannabinoid system in
the regulation of the hypothalamo-pituitary-adrenal axis in rodents is well
documented, the precise role played by the cannabinoid type one (CB(1)) receptor
in this effect has not been fully elucidated. Consequently, we investigated the
role of CB(1) receptor in modulating plasma corticosterone concentrations through
use of the potent and selective CB(1) receptor antagonist SR141716A and CB(1)
receptor knockout mice. Rats were administered SR141716A (0.1, 0.3, and 1 mg/kg,
i.v.) and blood was sampled at 0, 15, 60, 90 and 120 min postinjection. SR141716A
dose- and time-dependently increased plasma corticosterone levels and maximum
effects were obtained with the 1 mg/kg dose 60 min postinjection. In mice,
SR141716A (0.1, 0.3, 1, 3, and 10 mg/kg, i.p.) also induced a dose-dependent rise
in corticosterone levels 60 min postinjection; this rise reached plateau levels
with the 0.3-1 mg/kg doses. The stimulatory effect of SR141716A (1 mg/kg, i.p.)
on plasma corticosterone 60 min postinjection was abolished in the CB(1) receptor
knockout mice, which did not show any difference in basal corticosterone levels
as compared to their wild-type controls. Finally, the stimulatory effects of
SR141716A (10 mg/kg, i.p.) on plasma corticosterone 60 min postinjection were
retained after subchronic dosing (5 days, once daily) in mice. The present
results indicate that SR141716A increases plasma corticosterone in rats and mice
possibly through blockade of CB(1) receptors, an effect that is retained after
subchronic dosing in mice. These data provide support for the notion that changes
in plasma corticosterone concentrations may be used in the laboratory and the
clinic to assess the effects of CB(1) receptor antagonism.
PMID- 17030029
TI - In vitro anti-tumour effect of 1,10-phenanthroline-5,6-dione (phendione),
[Cu(phendione)3](ClO4)2.4H2O and [Ag(phendione)2]ClO4 using human epithelial cell
lines.
AB - The anti-cancer chemotherapeutic potential of 1,10-phenanthroline-5,6-dione
(phendione), [Cu(phendione)(3)](ClO(4))(2).4H(2)O and [Ag(phendione)(2)]ClO(4)
were determined using four human cells lines, i.e. two neoplastic (A-498 and Hep
G2) and two non-neoplastic (CHANG and HK-2). All of the phendione derivatives
induced a concentration-dependant decrease in the viability of the four cell
lines, with [Cu(phendione)(3)](ClO(4))(2).4H(2)O displaying greatest activity. In
comparative studies, IC(50) values obtained with the two neoplastic cell lines
showed a cytotoxic response which was between 3 and 35 times greater than that
observed for the metal-based anti-cancer agent, cisplatin. Furthermore, metal
phendione complexes, rather than simple solvated metal ions, were responsible for
the observed cytotoxicity. Despite the high level of potency associated with
these compounds they did not display an apparent cyto-selective profile, as they
reduced the viability of both neoplastic and non-neoplastic cells. However,
selected mechanistic studies showed that phendione and its metal complexes
inhibited DNA synthesis which did not appear to be mediated through
intercalation. Ames testing highlighted that all three compounds and their phase
I metabolites were non-mutagenic, unlike cisplatin. Taken together, these results
suggest that phendione and its Cu(II) and Ag(I) complexes may be capable of
acting as highly effective anti-cancer therapies, which with careful
administration could provide very potent and effective alternatives to cisplatin.
PMID- 17030032
TI - Measuring quality in trauma care.
AB - For use in quality measurement, a quality indicator (QI) must satisfy a number of
criteria: there needs to be an established link with outcome; the indicator needs
to measure what is considered current accepted practice; the targeted population
requires precise definition; an appropriate risk adjustment strategy must be
employed; the indicator should be feasible for collection; and, the measure must
apply to a sufficient number of people so as to provide a measure of system-wide
quality. This article discusses the use of QIs in the care of trauma patients. A
series of QIs were originally promulgated by the American College of Surgeons
Committee on Trauma (ACSCOT) and have been investigated for their utility in
measuring quality in trauma systems by a number of US based studies. While some
have advocated the implementation of several specific indicators, others have
recommended discontinued use of a range of proposed QIs. This review highlights
the difficulties of meeting these ideal indicator requirements in trauma care and
proposes that the development of alternative indicators may provide more useful
measures of quality care.
PMID- 17030031
TI - Antinociceptive action of (+/-)-cis-(6-ethyl-tetrahydropyran-2-yl)-formic acid in
mice.
AB - The objective of this study was to investigate spinal and supraspinal
antinociceptive effects of a new synthetic compound, (+/-)-cis-(6-ethyl
tetrahydropyran-2-yl)-formic acid (tetrahydropyran derivative). Its activity was
compared with those from morphine. In peripheral models of inflammation and
hyperalgesia, tetrahydropyran derivative significantly reduced nociceptive effect
induced by acetic acid or formalin in mice. Tetrahydropyran derivative developed
antinociceptive effect on the tail-flick and hot-plate tests with a long-acting
curve maintaining the effect for 4 h longer than morphine. The opioid receptor
antagonist naloxone totally reverted tetrahydropyran derivative effects on both
models. Morphine as well as tetrahydropyran derivative induced tolerance and
sedation in mice. However, tetrahydropyran derivative-induced tolerance had its
onset retarded and the sedative activity was lower when compared to that induced
by morphine. These results indicate that this new substance develops an
antinociceptive activity and may be used in the future as a substitute for
traditional opioids.
PMID- 17030033
TI - Eimeria tenella enolase and pyruvate kinase: a likely role in glycolysis and in
others functions.
AB - Two cDNA codings for glycolytic enzymes were cloned from a cDNA library
constructed from the schizont stage of the avian parasite Eimeria tenella.
Enolase and pyruvate kinase cDNA were fully sequenced and compared with sequences
of enzymes from other organisms. Although these enzymes were already detected in
the sporozoite stage, their expression was enhanced during the first schizogony
in accordance with the anaerobic conditions of this part of the life cycle of the
parasite. Under activating conditions, microscopic observations suggest that
these glycolytic enzymes were relocalised inside sporozoites and moreover were in
part secreted. The enzymes were also localised at the apex of the first
generation of merozoites. Enolase was partly observed inside the nucleus of
sporozoites and schizonts. Taken together, these results suggest that glycolytic
enzymes not only have a function in glycolysis during anaerobic intracellular
stages but may also participate in the invasion process and, for enolase, in the
control of gene regulation.
PMID- 17030034
TI - Pro-apoptotic low-density lipoprotein subfractions in type II diabetes.
AB - OBJECTIVE: To test the hypothesis that differences in subfractions of circulating
lipoproteins between diabetic and non-diabetic subjects exist and might
contribute to the increased risk for atherosclerosis in type II diabetics.
METHODS AND RESULTS: LDL isolated from diabetic (D) and control subjects (N) were
separated by FPLC into five subfractions (L1-L5). The fractional distributions of
N- and D-LDL were not different, but the most strongly retained subfractions of D
LDL (D-L5) were markedly more pro-apoptotic to bovine aortic endothelial cells in
vitro than were the other subfractions in D- or N-LDL. D-L5 induced time- and
concentration-dependent apoptosis that was inhibited by z-VAD-fmk. The most
electronegative D-LDL subfractions contained substantial amounts of apoproteins
AI, E and CIII, higher concentrations of non-esterified fatty acids and LpPLA2,
and lower trinitrobenzenesulfonic acid (TNBSA) reactivities. Electronegative
subfractions of D-LDL exhibited longer lag times and lower net increases in
absorbance at 234 nm with Cu-catalyzed oxidation in vitro. CONCLUSIONS: The
toxicities of electronegative subfractions of LDL from diabetic subjects to
endothelial cells in vitro may be pivotal to vascular complications of diabetes
in vivo, but the specific molecular alterations responsible for the toxicities of
these subfractions of diabetic LDL are not known.
PMID- 17030036
TI - Visualising viscous fingering in chromatography columns: high viscosity solute
plug.
AB - The interface between two fluids that have different viscosities and are
percolating through a porous bed is unstable. Sooner or later, a flow instability
termed viscous fingering (VF) develops. This phenomenon is important in
chromatography because the solute plug does not have the same viscosity as the
mobile phase. Because the sample is often much more viscous than the mobile
phase, it is the interface at the rear of the sample band that is usually
unstable. This situation is frequent in many modes of chromatography, e.g., in
preparative and in multidimensional chromatography, in size exclusion
chromatography, in frontal analysis, and in other physicochemical measurements
(e.g., determination of adsorption isotherms and of mass transfer parameters).
When the solute plug is more viscous than the mobile phase, we observed that the
solute band compressed. When the viscosity contrast increased up to 0.30 cP,
fingers appeared to trail behind the solute plug. The development of fingers then
became more substantial as the viscosity contrast increased. To avoid effects
associated with VF, the mobile phase and the solute plug should have nearly the
same viscosity.
PMID- 17030037
TI - Factors influencing newborns' preference for faces with eye contact.
AB - We investigated newborns' sensitivity to the direction of gaze of another's face
by using a preferential looking technique. This study extends earlier work on a
preference for faces with direct gaze in newborns. In Experiment 1, we replicate
the basic finding of Farroni and colleagues that newborns prefer to look at faces
with direct gaze. In Experiments 2 and 3, we establish that a preference for
faces with direct gaze in newborns is present only within the context of an
upright face and a straight head, suggesting that relatively primitive
configuration-sensitive mechanisms may be operating. Overall, these results
further the view that relatively simple perceptual biases in newborns may be an
essential foundation for later social-cognitive development.
PMID- 17030035
TI - Carotid artery plaque thickness is associated with increased serum calcium
levels: the Northern Manhattan study.
AB - BACKGROUND: Elevated serum calcium concentrations are associated with vascular
calcification and cardiovascular disease. It is unknown whether there is a
relationship between high-normal serum calcium levels and sub-clinical vascular
effects. We investigated the association between serum calcium and carotid plaque
thickness, a powerful early predictor of clinical coronary and cerebrovascular
events. METHODS: Epidemiological study of 1194 subjects from the Northern
Manhattan Study cohort, a prospective community-based study designed to
investigate risk factors for vascular disease in different race-ethnic groups.
RESULTS: Subjects with carotid plaque had higher corrected serum calcium levels
within the normal range than those without carotid plaque (2.21+/-0.09 mmol/L
versus 2.19+/-0.09 mmol/L, p<0.002). The relationship between carotid plaque and
serum calcium persisted after adjustment for traditional cardiovascular risk
factors. Subjects in the top quintile of maximal carotid plaque thickness
(>or=1.7 mm) were more likely to be in the highest quintile of serum calcium
level (OR=1.64, 95% CI=1.17-2.29, p<0.004). The interaction of age and corrected
serum calcium was the most significant predictor of carotid plaque thickness when
traditional vascular risk factors were considered (p<0.001). CONCLUSIONS: Serum
calcium levels in a multi-ethnic population of older men and women were
positively associated with carotid plaque thickness, a powerful early predictor
of clinical coronary and cerebrovascular events.
PMID- 17030038
TI - Time monitoring and executive functioning in children and adults.
AB - This study examined time-based prospective memory performance in relation to
individual and developmental differences in executive functioning. School-age
children and young adults completed six experimental tasks that tapped three
basic components of executive functioning: inhibition, updating, and mental
shifting. Monitoring performance was examined in a time-based prospective memory
task in which participants indicated the passing of time every 5min while
watching a movie. Separate analyses of the executive functioning data yielded a
two-factor solution for both age groups, with the updating and inhibition tasks
constituting a common factor and the shifting tasks constituting a separate
factor. Both children and adults showed accelerating monitoring functions with
low rates of clock checking during the early phase of each 5-min interval.
However, compared with adults, children needed more clock checks for obtaining
the same level of response accuracy. Executive functioning had selective effects
on time-based prospective memory performance. In both children and adults,
monitoring performance was related to the inhibition and updating components, but
not to the shifting component, of executive functioning. We conclude that
difficulties in temporary maintenance and updating of working memory contents may
create discontinuities in sense of time, leading to an increased reliance on
external cues for time keeping.
PMID- 17030039
TI - Connections, connections, connexins: towards systems biology paradigm of cardiac
arrhythmia.
PMID- 17030040
TI - A thiol labelling competition experiment as a probe for sidechain packing in the
kinetic folding intermediate of N-PGK.
AB - Protein folding is directed by the sequence of sidechains along the polypeptide
backbone, but despite this the developement of sidechain interactions during
folding is not well understood. Here, the thiol-active reagent, dithio
nitrobenzoic acid (DTNB), is used to probe the exposure of the cysteine sidechain
thiols in the kinetic folding intermediates of the N-terminal domain of
phosphoglycerate kinase (N-PGK) and a number of conservative (I-, L-, or V-to-C)
single cysteine variants. Rapid dilution of chemically denatured protein into
folding conditions in the presence of DTNB allowed the degree of sidechain
protection in any rapidly formed intermediate to be determined through the
analysis of the kinetics of labelling. The protection factors derived for the
intermediate(s) were generally small (<25), indicating only partial burial of the
sidechains. The distribution of protection parallels the previously reported
backbone amide protection for the folding intermediate of N-PGK. These
observations are consistent with the hypothesis that such intermediates resemble
molten globule states; i.e. with native-like backbone hydrogen bonding and
overall tertiary structure, but with the sidechains that make up the hydrophobic
protein core dynamic and intermittently solvent exposed. The success of the
competition technique in characterizing this kinetic intermediate invites
application to other model systems.
PMID- 17030041
TI - Global analyses of evolutionary dynamics and exhaustive search for social norms
that maintain cooperation by reputation.
AB - Reputation formation is a key to understanding indirect reciprocity. In
particular, the way to assign reputation to each individual, namely a norm that
describes who is good and who is bad, greatly affects the possibility of
sustained cooperation in the population. Previously, we have exhaustively studied
reputation dynamics that are able to maintain a high level of cooperation at the
ESS. However, this analysis examined the stability of monomorphic population and
did not investigate polymorphic population where several strategies coexist.
Here, we study the evolutionary dynamics of multiple behavioral strategies by
replicator dynamics. We exhaustively study all 16 possible norms under which the
reputation of a player in the next round is determined by the action of the self
and the reputation of the opponent. For each norm, we explore evolutionary
dynamics of three strategies: unconditional cooperators, unconditional defectors,
and conditional cooperators. We find that only three norms, simple-standing,
Kandori, and shunning, can make conditional cooperation evolutionarily stable,
hence, realize sustained cooperation. The other 13 norms, including scoring,
ultimately lead to the invasion by defectors. Also, we study the model in which
private reputation errors exist to a small extent. In this case, we find the
stable coexistence of unconditional and conditional cooperators under the three
norms.
PMID- 17030042
TI - Isometric contraction of microvascular pericytes from mouse brain parenchyma.
AB - Pericytes were isolated and cultured from mouse cerebroparenchymal microvessels.
A single pericyte clone was three-dimensionally cultured in a collagen gel by
adding tensile stress, resulting in the reconstruction of narrow stringy fibers.
When the contractility of these fibers was evaluated isometrically, they
contracted in response to acetylcholine (ACh)1 or noradrenaline; this was
accompanied by an increase in intracellular calcium concentration ([Ca(2+)]i).
The fibers that were pre-contracted by ACh were completely relaxed by papaverine,
which is a smooth-muscle relaxant. Moreover, the muscarinic ACh receptor
antagonist atropine depressed the [Ca(2+)]i response that was induced by ACh.
This study demonstrates for the first time the quantitative measurement of the
contractions produced by cultured microvascular pericytes from mouse brain
parenchyma.
PMID- 17030043
TI - Change in shear stress (Deltatau)/hydraulic conductivity (Lp) relationship after
pronase treatment of individual capillaries in situ.
AB - A complex glycoprotein meshwork covers the inner wall of blood vessels and is
implicated in mechanotransduction of fluid shear stress (tau). A relationship
between Deltatau and capillary Lp has been established. The purpose of this study
was to evaluate Lp in response to Deltatau after exposing the capillary lumen to
a mild, non-specific protease selected to disrupt its inner matrix. We
hypothesized that Lp would not correlate with Deltatau after enzyme treatment.
Frogs (Rana pipiens, n=69) were pithed and the mesentery was exteriorized. Lp was
assessed at 30 cm H2O using the modified Landis technique after an abrupt, square
wave Deltatau produced by a physiologically relevant increase in pressure.
Perfusate solutions were 10 mg ml-1 BSA/frog Ringer's (Control) or 0.1 mg ml-1
pronase in BSA/Ringer's (1 min) then BSA/Ringer's alone (Test). Mean (+/-SE)
control Lp following Deltatau was 2.2+/-0.2 x 10(-7) cm s-1 cm H2O-1 and
individual values correlated positively with Deltatau (r=0.85, P<0.0001, n=41).
After pronase, mean Test Lp (17.6+/-2.5 x 10(-7) cm s-1 cm H2O-1) was higher
compared to control and Deltatau/Lp plots revealed two subsets of capillaries. Lp
correlated strongly with Deltatau in capillaries with diameters15 microm (r=0.96, P=0.0001, n=8). Slopes were 3.9- and 8.7-fold
higher, respectively, compared to control. These data suggest a protective role
for luminal constituents of intact capillaries. Mechanisms involved in capillary
responses to flow-induced, mechanical stimuli may be located in the cellular
structures that form capillaries.
PMID- 17030044
TI - Tonic adenosine A1 and A2A receptor activation is required for the excitatory
action of VIP on synaptic transmission in the CA1 area of the hippocampus.
AB - Adenosine can regulate synaptic transmission through modulation of the action of
other neurotransmitters. The influence of adenosine on VIP enhancement of
synaptic transmission in hippocampal slices was investigated. Facilitation of
fEPSP slope by 1 nM VIP (23.3+/-1.3%) was turned into an inhibition (-12.1+/
3.4%) when extracellular endogenous adenosine was removed using adenosine
deaminase (ADA, 1U/ml). Blockade of adenosine A(1) receptors with 1,3-dipropyl-8
cyclopentylxanthine (DPCPX, 10 nM) or of A(2A) receptors with ZM241385 (20 nM)
attenuated the effect of VIP. When both DPCPX and ZM241385 were present the
effect of VIP was abolished. In the presence of ADA, selective A(1) receptor
activation with N(6)-cyclopentyladenosine (CPA, 15 nM) or A(2A) receptor
activation with CGS21680 (10 nM) partially readmitted the excitatory effect of
VIP on fEPSPs. In contrast, facilitation of PS amplitude by 1 nM VIP (19.1+/
1.2%) was attenuated in the presence of ADA or DPCPX but was not changed by
ZM241385. CPA, in the presence of ADA, fully restored the effect of VIP on PS
amplitude. In conclusion, VIP facilitation of synaptic transmission to
hippocampal pyramidal cell dendrites is dependent on both A(1) and A(2A) receptor
activation by endogenous adenosine. VIP effects on PS amplitude are only
dependent on A(1) adenosine receptor activation. This differential sensitivity to
adenosine modulation might be due to the different VIP circuits contributing to
VIP effects on pyramidal cell dendrites and pyramidal cell bodies.
PMID- 17030045
TI - Primary reflex persistence in children with reading difficulties (dyslexia): a
cross-sectional study.
AB - The primary reflex system emerges during fetal life and is inhibited during the
first year after birth. Our aim was to examine the effects of persistence of this
early neurological system on the attainment of core literacy skills in dyslexic
and non-dyslexic poor readers. We assessed the prevalence of a persistent primary
reflex in a cross-sectional, representative sample of children (n=739) aged 7-9
years old attending mainstream primary school in Northern Ireland using
standardised educational tests, and a clinical diagnostic test for a primary
reflex (the asymmetrical tonic neck reflex (ATNR)). Multiple regression analyses,
involving all of the sample children, revealed that persistence of the ATNR was
significantly predictive of attainments in reading (t=-8.34, p<.001), spelling
(t=-8.00, p<.001), non-word reading (t=-16.15, p<.001), and verbal IQ (t=-4.71,
p<.001). ANOVA tests revealed that there were no differences between the
performance of dyslexic and non-dyslexic poor readers on any of the outcome
measures (reading (F(1, 289)=0.51, p=.48), spelling (F(1, 289)=0.02, p=.90), non
word reading (F(1, 289)=0.76, p=.38), ATNR level (F(1, 289)=2.54, p=.11)).
Further ANOVA tests revealed that males had significantly higher levels of
persistent reflex than females (F(1, 737)=15.21, p<.001), and that children from
socially disadvantaged backgrounds had significantly higher levels of reflex than
children who were not socially disadvantaged (F(1, 737)=20.84, p<.001). The
findings suggest that for many children in mainstream schooling, the attainment
of core educational skills may be affected by the persistence of a brainstem
mediated reflex system that should have been inhibited in the first year after
birth. Furthermore, these findings suggest that dyslexia is not a distinct
category of poor reading, and that it may be more valid to term all poor readers
as dyslexic irrespective of IQ.
PMID- 17030046
TI - Verb generation in children and adolescents with acute cerebellar lesions.
AB - The aim of the present study was to examine verb generation in a larger group of
children and adolescents with acute focal lesions of the cerebellum. Nine
children and adolescents with cerebellar tumours participated. Subjects were
tested a few days after tumour surgery. For comparison, a subgroup was tested
also 1 or 2 days before surgery. None of the children had received radiation or
chemotherapy at or before the time of testing. Eleven age- and education-matched
control subjects participated. Subjects had to generate verbs to blocked
presentations of photographs of objects. As control condition, the objects had to
be named. Furthermore, dysarthria was quantified by means of a sentence
production and syllable repetition task. Detailed analysis of individual 3D-MR
images revealed that lesions affected cerebellar hemispheres in all children and
adolescents. The right cerebellar hemisphere was affected in four and the left
hemisphere in five subjects. In the present study, naming and verb generation
accuracy were preserved in the majority of subjects with cerebellar lesions. No
significant signs of learning deficits were observed, as reduction of reaction
times over blocks was not different compared to controls. There was a trend of
children and adolescents with right-hemispheric lesions to perform worse compared
to controls. In this group, however, significant signs of dysarthria were
present. In sum, no significant signs of disordered verb generation were observed
in children and adolescents with acute cerebellar lesions. Findings suggest that
the role of the cerebellum in verb generation may be less pronounced than
previously suggested. Findings need to be confirmed in a larger group of subjects
with acute focal lesions.
PMID- 17030047
TI - Is Broca's area involved in the processing of passive sentences? An event-related
fMRI study.
AB - We used functional magnetic resonance imaging (fMRI) to investigate whether
activation in Broca's area is greater during the processing of passive versus
active sentences in the brains of healthy subjects. Twenty Japanese native
speakers performed a visual sentence comprehension task in which they were asked
to read a visually presented sentence and to identify the agent or the patient in
the sentence by pressing a button. We found that the processing of passive
sentences elicited no greater activation than that of active sentences in Broca's
area. However, passive sentences elicited greater activation than active
sentences in the left frontal operculum and the inferior parietal lobule. Thus,
our neuroimaging results suggest that deficits in the comprehension of passive
sentences in Japanese aphasics are induced not by lesions to Broca's area, but to
the left frontal operculum and/or the inferior parietal lobule.
PMID- 17030049
TI - Funding for prevention: A global perspective.
PMID- 17030048
TI - Exploring the functional and anatomical bases of mirror-image and anatomical
imitation: the role of the frontal lobes.
AB - Humans are the most imitative species on earth, but how imitation is accomplished
and which areas of the brain are directly involved in different kinds of
imitation is still under debate. One view is that imitation entails representing
observed behaviours as a set of hierarchically organised goals, which
subsequently drive the construction of an action pattern [Bekkering, H.,
Wohlschlager, A., & Gattis, M. (2000). Imitation of gestures in children is goal
directed. The Quarterly Journal of Experimental Psychology, 53, 153-164;
Wohlschlager, A., Gattis, M., & Bekkering, H. (2003). Action generation and
action perception in imitation: An instance of the ideomotor principle.
Philosophical Transactions of the Royal Society of London, 358, 501-515]. On this
view, when working memory resources are limited, only the goals at the top-end of
the hierarchy will be accurately reproduced. In the present study, neurologically
intact participants and patients with frontal and non-frontal lesions were asked
to make imitative responses that were either mirror-image (e.g., the observer's
right side corresponding to the model's left side) or anatomically (e.g., the
observer's right side corresponding to the model's right side) matching.
Experiment 1 confirmed that individuals with brain damage, though globally
impaired compared with neurologically intact controls, nevertheless followed the
same goal hierarchy. However, there was a selective deficit in performing
anatomical imitation for the frontal group. Experiment 2 demonstrated that the
problem for frontal patients stemmed from an impaired ability to remember and
reproduce incompatible stimulus-response mappings, which is fundamental for the
selection of the appropriate frame of reference during anatomical imitation.
PMID- 17030050
TI - Factors accounting for the rise in health-care spending in the United States: the
role of rising disease prevalence and treatment intensity.
AB - OBJECTIVES: To examine the factors responsible for the rise in health- care
spending in the United States over the past 15 years. STUDY DESIGN AND METHODS:
Nationally representative survey data from 1987 and 2003 were used to examine the
top medical conditions accounting for the rise in spending. I also estimate how
much of the rise is traced to rising treated disease prevalence and rising
spending per case. RESULTS: The study finds most of the rise in spending is
linked to rising rates of treated disease prevalence. The rise in prevalence is
associated with the doubling of obesity in the US and changes in clinical
thresholds for treating asymptomatic patients with certain cardiovascular risk
factors. CONCLUSIONS: Most of the policy solutions offered in the US to slow the
growth in spending do not address the fundamental factors accounting for spending
growth. More aggressive efforts for slowing the growth in obesity among adults
and children should be centre-stage in the efforts to slow the rise in health
care spending.
PMID- 17030051
TI - Regulation of estrogen receptor alpha by estradiol in pregnant and estradiol
treated rats.
AB - Estrogens play an important role in tissue metabolism through specific regulation
of several intracellular pathways. We studied ERalpha regulation in muscle and
adipose tissue from pregnant and estradiol treated rats. In both groups, we
identified three different ERalpha inmunoreactive proteins (80, 67 and 46 kDa)
using total protein extracts. Because it has been showed that estrogens are able
to promote rapid effects in several cellular models, we looked for three ERalpha
related proteins at plasma membrane. In skeletal muscle of both groups, we
positively identified the three ERalpha-related isoforms in plasma membrane, but
in adipose tissue from pregnant we were not able to identify ERalpha67, and in
estradiol treated animals ERalpha80 was absent. Taking together, our results
showed a tissue-specific regulation of whole-cell ERalpha-related proteins and
ERalpha located at plasma membrane, which should be involved in non-genomic
actions of 17beta-estradiol. The role of the three ERalpha inmunoreactive
proteins is unknown, however, seems probably related to rapid activation of
signalling pathways.
PMID- 17030052
TI - HgeTx1, the first K+-channel specific toxin characterized from the venom of the
scorpion Hadrurus gertschi Soleglad.
AB - A novel toxin was identified, purified and characterized from the venom of the
Mexican scorpion Hadrurus gertschi (abbreviated HgeTx1). It has a molecular mass
of 3950 atomic mass units (a.m.u.) and contains 36 amino acids with four
disulfide bridges established between Cys1-Cys5, Cys2-Cys6, Cys3-Cys7 and Cys4
Cys8. It blocks reversibly the Shaker B K(+)-channels with a Kd of 52nM. HgeTx1
shares 60%, 45% and 40% sequence identity, respectively, with Heterometrus
spinnifer toxin1 (HsTX1), Scorpio maurus K(+)-toxin (maurotoxin) and Pandinus
imperator toxin1 (Pi1), all four-disulfide bridged toxins. It is 57-58% identical
with the other scorpion K(+)-channel toxins that contain only three disulfide
bridges. Sequence comparison, chain length and number of disulfide bridges
analysis classify HgeTx1 into subfamily 6 of the alpha-KTx scorpion toxins
(systematic name: alpha-KTx 6.14).
PMID- 17030053
TI - Twentieth century toxinology and antivenom development in Australia.
AB - It was not until the last decade of the 19th century that an experimental
approach (led by Bancroft in Queensland and Martin in Sydney and Melbourne)
brought a higher plane of scientific objectivity to usher in the modern era of
Australian toxinology. This Australia era, 1895-1905, coincided with and in some
respects was the result of the new knowledge emerging from Europe and the
Americas of the therapeutic effects of antitoxins. The subsequent systematic
study of Australian venoms and toxins through to the 1930s and beyond, by
Tidswell, Fairley, Ross, Kellaway and Cleland, set the foundation for Australia's
leading reputation in venom research. As elsewhere, this development was to
revolutionise the medical management of those victims who in the past had died in
Australia from our venomous and toxic fauna. Morgan, Graydon, Weiner, Lane and
Baxter at the Commonwealth Serum Laboratories emphasised the importance of
cooperation between those expert at catching and milking the venomous creatures
and those developing the antivenoms. Commercial antivenom manufacture began in
Australia in 1930 with the tiger snake antivenom. This was followed by other
antivenoms for the other important species (1955: taipan; 1956: brown snake;
1958: death adder; 1959: Papuan black snake; 1961: sea snake; 1962: polyvalent)
including the first marine antivenoms in the world (1956: stonefish antivenom;
1970: box jellyfish) culminating, in 1980, with the release of the funnel web
spider antivenom. More recent activity has focused on veterinary antivenoms and
production of new generation human antivenoms for export (CroFab and ViperaTAB).
This paper reviews some of the milestones of Australian toxinology, and antivenom
development in particular, during the 20th century.
PMID- 17030054
TI - Swainsonine-induced lysosomal storage disease in goats caused by the ingestion of
Turbina cordata in Northeastern Brazil.
AB - A disease of the central nervous system in goats was observed in the
municipalities of Juazeiro, Casa Nova and Curaca, state of Bahia, and Petrolina,
state of Pernambuco, Northeastern Brazil. The disease was produced experimentally
in two goats by the administration of dry Turbina cordata mixed with grain.
Clinical signs were observed after the ingestion of 62 and 106 g/kg body weight
in 28 and 54 days, respectively. The concentration of swainsonine in the plant
varied from less than 0.001% to 0.14% (dry weight). Clinical signs of natural and
experimental cases included difficulties in standing, ataxia, hypermetria, wide
based stance, intention tremors, spastic paresis mainly in the hind legs,
nystagmus, abnormal postural reactions, head tilting, and falling. Diffuse
vacuolation of neurons, epithelial cells of pancreas, thyroids, and renal tubules
were observed on the histology. From the electron microscopy of Purkinje cells
the vacuoles represented dilated lysosomes. These findings demonstrated that T.
cordata causes an acquired glycoprotein lysosomal storage disease. The
intoxication occurs at least in an area of 27,000 km2 causing severe losses in
goats, and some farmers report the disease also in cattle.
PMID- 17030055
TI - Decrease in toxicity of microcystins LA and LR in drinking water by ozonation.
AB - Unchlorinated treated waters from two Australian reservoirs were spiked with
microcystin-LA and -LR extracted from a toxic scum of Microcystis aeruginosa. The
two waters had considerably different water quality and therefore ozone demands.
The spiked sample waters were ozonated using the batch method of ozonation at a
range of doses and the samples were analysed for toxins using high-performance
liquid chromatography (HPLC). The toxin content of the samples was also
determined using a protein phosphatase type 2A inhibition assay (PP2A) and
toxicity via the standard mouse bioassay. The HPLC results correlated well with
the PP2A results and toxicity tests for both waters. A loss of both toxins and
toxicity was observed with increasing ozone dose, resulting in a complete loss of
toxicity for both waters once an ozone residual had been achieved. At this ozone
residual no toxin was detected using HPLC. The results indicate that microcystins
are not transformed into toxic by-products.
PMID- 17030056
TI - The mammalian fauna associated with an archaic hominin skullcap and later
Acheulean artifacts at Elandsfontein, Western Cape Province, South Africa.
AB - The Elandsfontein site, Western Cape Province, South Africa, is well known for an
archaic hominin skullcap associated with later Acheulean artifacts. The site has
also provided nearly 13,000 mammalian bones that can be identified to skeletal
part and taxon. The assemblage derives from 49 species, 15 of which have no
historic descendants. Comparisons to radiometrically dated faunas in eastern
Africa indicate an age between 1 million and 600 thousand years ago. Unique
features of the fauna, including the late occurrence of a dirk-toothed cat and a
sivathere, may reflect its geographic origin in a region that was notable
historically for its distinctive climate and high degree of biotic endemism.
Together, taxonomic composition, geomorphic setting, and pollen extracted from
coprolites indicate the proximity of a large marsh or pond, maintained by a
higher water table. The small average size of the black-backed jackals implies
relatively mild temperatures. The sum of the evidence places bone accumulation
during one of the mid-Pleistocene interglacials that were longer and cooler than
later ones, including the Holocene. The geomorphic context of the fauna presents
no evidence for catastrophe, and most deaths probably resulted from attritional
factors that disproportionately killed the young and old. However, only the
dental-age profile of long-horned buffalo supports this directly. Field
collection methods biased skeletal-part representation, but originally, it
probably resembled the pattern in the younger, marsh-edge Acheulean occurrence at
Duinefontein 2, 45 km to the south. Excavation there exposed multiple vertebral
spreads, which probably mark carcasses from which hominins or large carnivores
removed the meatier elements. Bone damage at both sites suggests that, despite
abundant artifacts, hominins were much less important than carnivores in the bone
accumulation. Together with limited observations from other sites, Elandsfontein
and Duinefontein provisionally suggest that Acheulean-age hominins obtained few
large mammals, whether by hunting or scavenging.
PMID- 17030057
TI - D-dimer level is associated with the extent of pulmonary embolism.
AB - OBJECTIVES: Our aim was to study the association between the level of D-dimer and
the severity of pulmonary embolism (PE) as determined by various biochemical and
radiological prognostic markers in order to investigate the potential value of D
dimer as a prognostic marker for the severity of PE. PATIENTS AND METHODS: PE was
diagnosed in 100 consecutive out-patients by multi-detector computerized
tomography. One patient was excluded and the final cohort consisted of 99
patients. Pulmonary Artery Obstruction Index (PAOI) and Right Ventricular/Left
Ventricular (RV/LV) ratio were assessed. RESULTS: The median value for D-dimer
was 5.0 mg/L (inter-quartile range: 1.8, 12.2). There was a significant
association between log D-dimer, and between log RV/LV (r=0.45), log PAOI
(r=0.5), and PaO(2) (r=0.40). The multivariate analysis showed an increased
association between log D-dimer and between log RV/LV ratio (r=0.54) and log PAOI
(r=0.52) after adjusting for age, gender and for the duration of symptoms.
Significant association was found between the level of D-dimer and the most
proximal level of PE (p<0.0005). There was a significant dose-response
relationship between the level D-dimer and between Troponin-T and the frequency
of thrombolysis (p<0.0005). In the subgroup of patients with D-Dimer over the
upper quartile (>12.2), 12 (67%) patients had elevated Troponin-T and 8 (32%)
patients received thrombolysis, compared to 1 (5%) patient with elevated Troponin
T and none treated with thrombolysis in the subgroup of patients with D
dimeror=third line for 10
(31%) patients. RESULTS: Partial response was achieved in 5 (16%) patients,
stable disease in 8 (25%) and progressive disease in 19 (59%). Two patients with
stable disease and one patient with progressive disease while on previous
chemotherapy experienced a partial response with GEMOX regimen. The median
duration of response was 2.5 months (range, 1-11.5), the median time to tumor
progression 3 months (range, 1-18) and the median survival 5.6 months (range, 1
31). Grade III neutropenia occurred in five (16%) patients, grade III
thrombocytopenia in two (6%) and grade III anemia in three (9%); moreover, grades
II-III asthenia was reported in eight (25%) patients and grades II-III
neurotoxicity in three (9%). CONCLUSION: The GEMOX combination is a relatively
active and well tolerated second-line regimen in NSCLC patients pretreated with a
taxane- and/or platinum-based chemotherapy.
PMID- 17030076
TI - A peptide inhibitor of MurA UDP-N-acetylglucosamine enolpyruvyl transferase: the
first committed step in peptidoglycan biosynthesis.
AB - The MurA enzyme from Pseudomonas aeruginosa was purified to homogeneity and found
to be biologically active as a UDP-N-acetylglucosamine (UNAG) enolpyruvyl
transferase in a coupled enzyme assay where ATPase activity was measured by the
release of inorganic phosphate. A microtiter plate assay coupled to competitive
biopanning using the UDP-N-acetylglucosamine was used to screen 10(9) C-7-C and
12-mers peptides from phage display libraries. From 60 phage-encoded peptides
identified after the fourth round of biopanning, deduced amino acid sequences
were aligned and two peptides were synthesized and tested for inhibition of the
MurA-catalyzed reaction. The PEP 1354 peptide inhibited the ATPase activity of
MurA with an IC(50) value of 200muM and was found to be a competitive inhibitor
of UNAG. The pre-incubation of MurA with inhibitor indicated a time-independent
inhibition. This time-dependent inhibition is the first report of peptide
inhibitors of MurA, which represent the scaffold for the synthesis of inhibitory
peptidomimetic molecules.
PMID- 17030077
TI - The impact of active/cooperative instruction on beginning nursing student
learning strategy preference.
AB - Rapid changes in the nursing field and high demand for practicing nurses put
pressure on nursing faculty to educate increasing numbers of nursing students,
often without corresponding increases in resources. Although the use of active
and cooperative instruction methods in the classroom has been associated with
improved student learning, these practices require increased effort on the part
of both faculty and students. In addition, little is known about whether these
methods influence student nurses' use of these more elaborative processing
strategies in their independent study. The purpose of this quasi-experimental
investigation was to identify the impact of incorporating active and cooperative
classroom instructional activities on student preference for teaching methods and
use of learning strategies in independent study. A convenience sample of
beginning baccalaureate nursing students at a large Mid-Atlantic University was
randomly assigned by the registrar to two class sections. Students in one section
received primarily active/cooperative instruction, while the other received
primarily traditional lecture-based instruction. Results indicated that student
nurses exposed to active/cooperative instructional methods had an increased
preference for these methods after a semester of instruction, while those exposed
to traditional instruction had a higher preference for traditional methods. In
addition, students participating in active class instruction reported increased
preference for more elaborative independent study strategies, although overall
preference for both groups indicated a reliance on surface study strategies of
memorization and recall. Implications for use of instruction and student testing
methodologies are presented.
PMID- 17030078
TI - Cross-protective immunity in mice induced by live-attenuated or inactivated
vaccines against highly pathogenic influenza A (H5N1) viruses.
AB - Because of the time required to identify and produce an antigenically well
matched pandemic vaccine, vaccines that offer broader cross-reactive immunity and
protection are desirable. We have compared a live attenuated influenza vaccine
(LAIV) and inactivated influenza vaccine (IIV) based on a related H5
hemagglutinin (HA) from a nonpathogenic avian influenza virus,
A/Duck/Pottsdam/1042-6/86 (H5N2), for the ability to induce cross-reactive
immunity and/or cross-protective efficacy against a contemporary highly
pathogenic H5N1 viruses. Both LAIV and IIV provided cross-protection from
systemic infection, severe disease, and death following lethal challenges with
antigenically distinct A/Vietnam/1203/2004 (VN/1203) virus. Substantial levels of
serum anti-VN/1203 HA IgG were detected in mice that received either IIV or LAIV,
while nasal wash anti-VN/1203 HA IgA was detected in mice that received LAIV.
Formulation of IIV with alum adjuvant augmented neutralizing antibody responses
and protective efficacy. These results demonstrated that vaccination of mice with
H5 IIV or LAIV induced a high degree of cross-protection from illness and death
following lethal challenges with a heterologous H5N1 virus.
PMID- 17030079
TI - Changing epidemiology of invasive pneumococcal disease in central Australia prior
to conjugate vaccine: a 16-year study.
AB - This study reports a 16-year prospective surveillance of invasive disease
isolates in central Australian Aborigines. There were 621 (89.6% of total)
isolates recovered from Aborigines. The mortality in children less than 5 years
of age was 4% but rose to 34.5% in those over 49 years of age. The study
documented continuing high rates of disease overall, but with significant
reductions in incidence rates for children. In children under 2 years of age, the
incidence fell by 32% from 2053 per 100,000 in the period 1985-1990 to 1184 per
100,000 in the period 1996-2000. Rates of disease in adults showed no reduction
despite an adult immunisation programme with 23 valent vaccine which occurred in
the 1990s. Epidemics of serotypes 1, 5 and 12F were documented during the study
period.
PMID- 17030080
TI - What difference might sewage treatment performance make to endocrine disruption
in rivers?
AB - An assessment of the steroid estrogen removing performance of 23 different sewage
treatment plants (STPs) was performed. The assessment relied on a model to
estimate influent concentrations, and completed questionnaires on the STP
treatment details from the relevant water companies. This information was
compared with observed effluent 17beta-estradiol (E2) and estrone (E1)
concentrations. The 10 biological filter plants (BFP) in the study performed
poorly with only 30% (SD 31) removal on average for E1. This reduced E1 removal
performance of the BFPs compared to all the other STP types in the survey was
statistically significant (p<0.001). Scenarios of all the STPs as activated
sludge types, and one as all BFP types were modelled using the GREAT-ER model set
up for the Aire/Calder catchment in the UK. This difference was shown to have an
important effect on predicted river E1 concentrations and consequent risk
classifications.
PMID- 17030081
TI - [Surgical management of cutaneous malignant melanoma. Review].
AB - Nowadays managing a cutaneous malignant melanoma can concern different kind of
physicians: dermatologists, general or plastic surgeons The primary surgical
procedure is a major step of the treatment. Biopsy must be total to properly
determine the thickness of the tumor in case of malignancy. Wide local excision
of the scar is often necessary to decrease the local and general recurrence
rates. Wide local excision must be performed conforming to its own surgical
rules. Managing tumor located on the face or limb extremities is a matter of
plastic surgery. Sentinel node biopsy has succeeded to elective lymph node
dissection. This procedure allows research of lymphatic spreading of the disease.
Practice of sentinel node biopsy must be achieved in a protocolar way. Topography
of the lesion can modified achievement and results of this procedure. Prognosis
benefit of sentinel biopsy is now clear. Elective lymph node dissection is only
performed in case of invaded sentinel node or clinically invaded lymph nodes.
Local or locoregional recurrences mainly respond to surgical treatment using wide
excision. However, alternative solutions are being evaluated (isolated limb
perfusion).
PMID- 17030082
TI - Noradrenergic pain modulation.
AB - Norepinephrine is involved in intrinsic control of pain. Main sources of
norepinephrine are sympathetic nerves peripherally and noradrenergic brainstem
nuclei A1-A7 centrally. Peripheral norepinephrine has little influence on pain in
healthy tissues, whereas in injured tissues it has variable effects, including
aggravation of pain. Its peripheral pronociceptive effect has been associated
with injury-induced expression of novel noradrenergic receptors, sprouting of
sympathetic nerve fibers, and pronociceptive changes in the ionic channel
properties of primary afferent nociceptors, while an interaction with the immune
system may contribute in part to peripheral antinociception induced by
norepinephrine. In the spinal cord, norepinephrine released from descending
pathways suppresses pain by inhibitory action on alpha-2A-adrenoceptors on
central terminals of primary afferent nociceptors (presynaptic inhibition), by
direct alpha-2-adrenergic action on pain-relay neurons (postsynaptic inhibition),
and by alpha-1-adrenoceptor-mediated activation of inhibitory interneurons.
Additionally, alpha-2C-adrenoceptors on axon terminals of excitatory interneurons
of the spinal dorsal horn possibly contribute to spinal control of pain. At
supraspinal levels, the pain modulatory effect by norepinephrine and
noradrenergic receptors has varied depending on many factors such as the
supraspinal site, the type of the adrenoceptor, the duration of the pain and
pathophysiological condition. While in baseline conditions the noradrenergic
system may have little effect, sustained pain induces noradrenergic feedback
inhibition of pain. Noradrenergic systems may also contribute to top-down control
of pain, such as induced by a change in the behavioral state. Following injury or
inflammation, the central as well as peripheral noradrenergic system is subject
to various plastic changes that influence its antinociceptive efficacy.
PMID- 17030083
TI - Serological and virological profile of chronic HBV infected women at reproductive
age in Greece. A two-year single center study.
AB - OBJECTIVE: Seroprevalence of HBsAg in 26,746 women at reproductive age in Greece
and evaluation of HBeAg/anti-HBe serological status as well as serum HBV-DNA
levels in a subgroup of HBsAg(+) women at labor. STUDY DESIGN: Serological
markers were detected using enzyme immunoassays. Serum HBV-DNA was calculated
using a sensitive quantitative PCR assay, with a lower limit of quantification of
200 copies/ml. RESULTS: Overall, 1.53% of women were HBsAg(+) and the majority of
them (64.96%) were Albanian. Among Albanian women the mean prevalence of HBsAg
was 4.9%, 5.57% among Asian women, and 1.29% among women from Eastern European
countries. The prevalence of HBsAg among African (0.29%) and Greek women (0.57%)
was very low and significantly lower in comparison with the mean value of the
studied population. Only 2.67% of HBsAg(+) women were HBeAg(+). Of a subgroup of
women in labor with available serum samples 28.6% had undetectable levels of
viremia (<200 copies/ml) and 15.9% had extremely low levels of viral replication
(<400 copies/ml). Only 12.7% of pregnant women evaluated at labor exhibited
extremely high serum HBV-DNA levels (>10,000,000 copies/ml) whereas 42.8% of them
exhibited HBV-DNA levels between 1500 and 40,000 copies/ml. CONCLUSIONS: The
overall prevalence of HBsAg is relatively low among women at reproductive age in
Greece but is higher among specific ethnic populations (Asian, Albanian). The
HBeAg(-)/antiHBe(+) serological status is a finding observed in the vast majority
of HBsAg(+) women of our study population, and a significant percentage of them
(approximately 44.5%) exhibit extremely low or even undetectable levels of viral
replication at labor, suggesting possibly that only a proportion of HBsAg(+)
women in Greece exhibit an extremely high risk of vertical transmission of the
infection.
PMID- 17030084
TI - Information about a form (on the dynamic laws of morphogenesis).
AB - How a developing embryo becomes "informed" about its form?" This problem remains
obscure and controversial. We argue that the "information about a form" is
distributed throughout three main components: the dynamic laws, the parameters
and the initial/boundary conditions. In the absence of a dynamic law two other
components are "blind", that is, do not contain any unambiguous information. We
present a version of a dynamic law of morphogenesis, based upon the presumption
of a feedback between passive and active mechanical stresses. We explore several
models of shape formation based upon this law and show that, as depending upon
the parameters values, they generate a large set of realistic shapes. Genetic and
epigenetic basis of the models parameters is discussed.
PMID- 17030085
TI - Temporal sub units in dendritic trees.
AB - This simulation study examines the possibility that dendritic sub units can be
defined according to temporal aspects in the timing of populations of synaptic
inputs. A two cell model with passive dendritic trees is used, which is subject
to both common and independent synaptic inputs, the presence of common synaptic
input results in a tendency for correlated firing in the two cell model. The
strength of this correlation is used to measure the efficacy of the common
synaptic inputs in modulating the output discharge of each neurone. Our results
suggest that a small fraction of the total synaptic input can effectively
modulate the timing of output spikes, this phenomenon is not dependent on the
physical location of the inputs on the dendritic tree. This phenomenon depends on
the presence of temporal correlation between the pre-synaptic spike trains that
provide the common input. We propose to refer to these as temporal sub units.
PMID- 17030086
TI - Unidirectional movement of an actin filament taking advantage of temperature
gradients.
AB - An actin filament with heat acceptors attached to its Cys374 residue in each
actin monomer could move unidirectionally even under heat pulsation alone, while
in the total absence of both ATP and myosin. The prime driver for the movement
was temperature gradients operating between locally heated portions on an actin
filament and its cooler surroundings. In this report, we investigated how the
mitigation of the temperature gradients induces a unidirectional movement of an
actin filament. We then observed the transversal fluctuations of the filament in
response to heat pulsation and their transition into longitudinally
unidirectional movement. The transition was significantly accelerated when Cys374
and Lys336 were simultaneously excited within an actin monomer. These results
suggest that the mitigation of the temperature gradients within each actin
monomer first went through the energy transformation to transversal fluctuations
of the filament, and then followed by the transformation further down to
longitudinal movements of the filament. The faster mitigation of temperature
gradients within actin monomer helps build up the transition from the transversal
to longitudinal movements of the filament by coordinating the interaction between
the neighboring monomers.
PMID- 17030087
TI - LH receptor gene mutations and polymorphisms: an overview.
PMID- 17030088
TI - APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling
complex.
AB - A number of signaling proteins have been demonstrated to interact with follicle
stimulating hormone (FSH) receptor (FSHR), including APPL1, 14-3-3tau and Akt2.
To further define the repertoire of proteins involved in FSH-induced signal
transduction, several signaling and adapter proteins were examined for the
ability to associate with FSHR. This report shows that, in addition to APPL1,
FSHR interacts with FOXO1a and APPL2. Moreover, APPL1 and APPL2 associate with
one another via the N-terminus of APPL1, presumably via the Bin-Amphiphysin-Rvs
(BAR) domain. The interactions between FSHR and APPL2 and between FSHR and FOXO1a
evidently are distinct since FOXO1a does not associate with either APPL1 or with
APPL2. Though APPL1 and APPL2 show some similarity in primary sequence, APPL1
associates with Akt2, whereas APPL2 does not. This is the first documented
difference in function between APPL1 and APPL2. These results suggest that FSHR,
APPL1, APPL2, Akt2 and FOXO1a are organized into distinct scaffolding networks in
the cell. Accordingly, the spatial organization of signaling and adapter proteins
with FSHR likely facilitates and finely regulates the signal transduction induced
by FSH.
PMID- 17030089
TI - Targeting novel and established therapies for non-small cell lung cancer.
AB - The prognosis in advanced non-small cell cancer (NSCLC) remains poor despite the
introduction of several new cytotoxic drugs in the past decade. New approaches
are required, and an improved understanding of lung cancer biology is identifying
molecular mechanisms that are potential targets for novel therapies. Antagonists
of signalling via the erbB and VEGFR families of transmembrane receptors have
promising activity in NSCLC, and survival benefit has already been demonstrated
for both erlotinib and bevacizumab. Although some patients enjoy dramatic and
sustained responses to some of the new targeted drugs, overall response rates in
unselected NSCLC patient groups are modest. This reflects the molecular
heterogeneity of the disease; further clinical progress will require improved
patient selection for treatment with both novel agents and established
chemotherapy drugs. Here, we review recent advances in NSCLC biology likely to
provide insight into such selection strategies.
PMID- 17030090
TI - Pressurized liquid extraction with water as a tool for chemical and toxicological
screening of soil samples at army live-fire training ranges.
AB - Significant discrepancies in the results of risk assessments based on chemical
and toxicity analyses of soils may arise through differences in the efficiency of
the extraction or leaching methods used. A rapid technique that may be used in
the screening phase of live-fire training ranges and suitable for extracting
explosive residues is pressurized liquid extraction (PLE) with water. Therefore,
PLE and the commonly used batch leaching method EN-124 57-2 were compared for
their utility to extract specific residues from soil samples collected from the
Canadian Forces Base (CFB) Petawawa, Ontario. After extraction the cytotoxicity
of the samples were assessed in the L-929 growth inhibition assay. The PLE method
yielded extracts suitable for direct use in the toxicity assay within 20 min as
compared to 24h for the batch leaching method. Analysis of the extracts showed
that the PLE water extracts tended to give higher recoveries of explosive
residues and the resulting exposure concentrations were confirmed by higher
cytotoxicities. Furthermore, gas chromatography-mass spectrometry analyses showed
that the samples contained significant amounts of several munition-related
stabilizers and plasticizers of toxicological significance in addition to the
analysed explosive residues. In conclusion, PLE using water is a promising
extraction technique for both chemical and toxicological screening of soil
samples from areas that may be contaminated with explosive residues.
PMID- 17030091
TI - Influence of chloride concentration on the formation of AOX in UV oxidative
system.
AB - In this study, the effects of chloride ion concentration and pH on UV oxidation
treatment were examined. Acetone and sodium dodecyl sulfate (ABS) were used as
organic substances. The treatment efficiencies of these chemicals by UV/H(2)O(2)
oxidation using a laboratory scale UV-free surface reactor (UV-FSR) with or
without Cl(-) addition at different pH values was compared. Results of this study
indicated that Cl(-) concentration and the chemical structure of the substances
are more decisive than pH in the oxidation process. There was no AOX at the start
of the experiments but as a result of oxidation a de novo synthesis of AOX was
observed, and these AOX(de novo) compounds were destroyed during the treatment.
Treatment was followed by TOC and AOX measurements. Approximately 98% and 95% TOC
removal efficiencies were obtained for the treatment of acetone and ABS
containing wastewaters, respectively.
PMID- 17030092
TI - Degradation characteristics of waste lubricants under different nutrient
conditions.
AB - We investigated the limits and extent of lubricants biodegradation at different
nutrient conditions and evaluated several soil biological activities with regard
to their usefulness for monitoring the bioremediation process in a soil
contaminated with lubricants. To examine the effects of nutrient addition on
lubricants biodegradation, a bench-scale investigation was conducted under
different nutrient conditions for over 105 days testing period. When nutrients
were added to contaminated soil with aged lubricant, great stimulation was
occurred in fertilized soil for hydrocarbon degradation activity compared to non
fertilized soil. At the end of the experiment (105 days after), the initial level
of contamination (9320+/-343 mg/kg) was reduced by 42-51% in the fertilized soil,
whereas, only 18% of the hydrocarbon was eliminated in the non-fertilized soil.
The effect of biostimulation of indigenous soil microorganisms declined with
time, apparently 42% of the initial concentration of hydrocarbon remained at the
end of experiment. Lubricants biodegradation process could be monitored well by
soil biological parameters. In fertilized soil, biological parameters (number of
HUB, soil respiration, dehydrogenase and catalase activities) were significantly
enhanced and correlated with each other, as well as the residual lubricant
concentration.
PMID- 17030093
TI - Sensorimotor adaptation to inertial forces in a multi-force environment does not
depend on the number of targets: indirect validation of the altered
proprioception hypothesis.
AB - The ability of our sensorimotor system to adapt to changing and complex
environmental demands has been under experimental scrutiny for more than a
century. Previous works have shown that aimed arm movements adapt quickly and
completely to Coriolis force, but incompletely to the combination of Coriolis and
centrifugal forces without visual cues. Two hypotheses may be advanced to explain
this discrepancy: the workspace-exploration hypothesis, and the degraded
proprioception hypothesis. The aim of this study was to distinguish between the
above two alternatives by comparing adaptive improvement during off-axis rotation
in subjects pointing at one, three or seven different targets in complete
darkness. Two main results emerge: (a) off-axis rotation led initially to errors
in the direction of Coriolis force and in the opposite direction of the
centrifugal force; (b) the size of the visited workspace has no effect on the way
the subjects adapt to a multi-force environment. The lack of a target-number
effect and the persistence of lateral errors in the pointing movements performed
during rotation of the platform, support the degraded-proprioception rather than
the workspace-exploration hypothesis of adaptation to a multi-force environment.
PMID- 17030094
TI - Shared cognitive processes underlying performance on the Wisconsin Card Sorting
Test and the Stroop Test in patients with schizophrenia: a measurement artifact?
AB - We explored the hypothesis that, while sensitive to different aspects of
executive functioning in patients with schizophrenia, the Wisconsin Card Sorting
Test (WCST) and the Stroop Test also measure the same construct, namely,
inhibitory control. Specifically, our goal was to confirm and extend previous
findings [A. Rossi, E. Daneluzzo, P. Mattei, M. Bustini, M. Cassachia, P.
Stratta, Wisconsin Card Sorting Test and Stroop performance in schizophrenia: a
shared construct, Neurosci. Lett. 226 (1997) 87-90] by demonstrating the
independence of this construct from other abilities necessary to successfully
perform the tasks. More importantly, we sought to improve on this previous study
by eliminating the influence of the variance of speed of responding. We examined
55 patients with schizophrenia and initially found that performance on the Stroop
Color-Word condition could, indeed, be predicted only by the percentage of
perseverative errors on the WCST, and not variables reflective of other cognitive
skills, thus replicating and extending previous findings. Once we removed the
influence of speed of responding from our measure, however, thus isolating the
inhibitory process, this finding disappeared. Therefore, our findings highlight
the importance of isolating the individual components of interest from complex
measures before drawing conclusions regarding the cognitive processes underlying
particular test performance.
PMID- 17030095
TI - Classical conditioning and expectancy in placebo hypoalgesia: a randomized
controlled study in patients with atopic dermatitis and persons with healthy
skin.
AB - The effectiveness of placebos is unchallenged. However, it is still not clear on
which mechanisms the placebo effect is based. Besides expectancy theories,
classical conditioning is discussed as a major explanatory model. In an
experimental conditioning design we tested 96 participants, 48 with atopic
dermatitis (24 male, 24 female) and 48 with healthy skin (24 male and 24 female).
All of them received a neutral ointment with a different briefing ("pain-reducing
ointment" versus "neutral ointment"). Electrical pain stimuli were subsequently
applied, which selectively induce a painful sensation. In the case of the
learning condition (classical conditioning) and unbeknown to the participants,
the intensity of the pain stimulus was reduced by 50% after the ointment had been
applied. The study addressed the question whether the pain experienced by the
patients with atopic dermatitis could be reduced through a placebo effect and
whether the placebo effect was achieved through expectancy or through a process
of classical conditioning or both. The results indicate that a placebo effect is
achieved via expectancy and classical conditioning. However, conditioning
processes seem to be necessary for a longer lasting effect. The extent of this
effect seemed to be greater in atopics than in healthy controls. Expectancy,
achieved through verbal instruction, might also be seen as a conditioned stimulus
that reactivates earlier stimulus associations.
PMID- 17030096
TI - Analgesic action of gabapentin on chronic pain in the masticatory muscles: a
randomized controlled trial.
AB - Chronic masticatory myalgia (CMM) can be defined as constant pain in the
masticatory muscles for more than 6 months and is influenced by the central
nervous system. The antiepileptic agent gabapentin acts centrally and is used for
managing different types of chronic pain conditions. The objective of this study
was to evaluate the analgesic action of gabapentin on CMM. In this 12-week
randomized controlled clinical trial 50 patients were randomly allocated into two
study groups: 25 received gabapentin and 25 received placebo. The outcome
measures utilized were pain reported on a VAS (VAS-pain), Palpation Index (PI)
and impact of CMM on daily functioning reported on a VAS (VAS-function). Thirty
six patients completed the study. Gabapentin showed to be clinically and
statistically superior to placebo in reducing pain reported by patients
(gabapentin=51.04%; placebo=24.30%; P=0.037), masticatory muscle hyperalgesia
(gabapentin=67.03%; placebo=14.37%; P=0.001) and impact of CMM on daily
functioning (gabapentin=57.70%; placebo=16.92%; P=0.022). It can be concluded
from this study that gabapentin is effective for the management of CMM.
PMID- 17030097
TI - Environmental exposure to bacteria and viruses may provide oncolytic protection
against cancers, and declining exposure to infections may contribute to a rising
incidence of cancer.
AB - Over the past century, the incidence of cancer rose markedly in developed
countries. Many underlying factors are known, but not all of them. Over the same
century, advances in public health and hygiene practically eradicated many
infectious illnesses, and exposure to some untargeted infectious agents has also
declined. There are reasons to suspect that these two trends are linked. Although
some viruses and one bacterium are known to be oncogenic, a high percentage of
infectious agents, 71% of viruses tested in one study, have shown oncolytic
properties. Some of these agents have minimal or no clinical consequences, and
some are - or were - quite ubiquitous. Many types of cancer are unusually
susceptible to several different agents, sometimes 10-1000 times more susceptible
than normal cells. When wild-type or attenuated viruses are used to treat cancer,
they are often more effective with smaller tumors, and it may be that nascent,
undetectable cancers are especially vulnerable. Environmental exposure to
bacteria and viruses may provide natural protection from cancer by attacking it
at this stage, or inducing the body to do so. Immunity to an infectious agent can
attenuate its oncolytic effect, but generally does not stop it, so both initial
and repeated exposures may be protective. As more direct evidence, treatment of
animals with selected live virus vaccines has provided protection from cancer,
and in humans, exposure to two specific infectious agents is known to correlate
with a reduced risk of cancer. The significant decline in exposure to infectious
agents over the past century may have inadvertently weakened this naturally
protective mechanism, driving cancer rates up. There is considerable research on
the impact of oncogenic agents, but surprisingly little regarding the impact of
oncolytic agents on cancer rates. An understanding of the relationship between
natural infections and the suppression of cancer may lead to prophylactic
measures against cancer, improved public health policies regarding vaccination
programs and hygiene, and greater insight into cancer treatment as well.
PMID- 17030098
TI - Hygiene hypothesis and protection against asthma in infants: spending time in the
countryside encountering natural allergens may boost maternal immunity.
PMID- 17030099
TI - Ghrelin may reduce radiation-induced mucositis and anorexia in head-neck cancer.
AB - Body weight loss is common in cancer patients, and is often associated with poor
prognosis, it greatly impairs quality of life (QOL). Radiation therapy (RT) is
used in head and neck cancers (HNC) either as a primary treatment or as an
adjuvant therapy to surgery. Patients with HNC are most susceptible to
malnutrition especially due to anorexia, which is aggravated by RT. Multiple pro
inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL
1beta), interferon (IFN)-gamma and tumor necrosis factor-alpha(TNF-alpha), have
been all associated with the development of both anorexia and oral mucositis.
Radiation-induced mucositis occurs in almost all patients, who are treated for
HNC, it could also cause weight loss. Ghrelin is a novel 28-amino acid peptide,
which up-regulates body weight through appetite control, increase food intake,
down-regulate energy expenditure and induces adiposity. Furthermore, ghrelin
inhibits pro-inflammatory cytokines such as IL-1alpha, IL-1beta, TNF-alpha which
may cause oral mucositis and aneroxia, which are the results of weight loss. Thus
weight loss during RT is an early indicator of nutritional decline, we propose
that recombinant ghrelin used prophylactically could be useful as an appetite
stimulant; and preventive of mucositis because of its anti-inflammatory effect,
it might help patients maintain weight over the course of curative RT of the HNC
and can improve specific aspects of QOL. This issue warrants further studies.
PMID- 17030100
TI - Abdominal aortic aneurysm and cerebral aneurysm present different pathological
evolutions and responses to pharmacological therapy.
AB - Over-degradation of extracellular components by matrix metalloproteinases (MMPs)
has been implicated as an important characteristic during the pathological
evolution of the abdominal aortic aneurysm (AAA) and cerebral aneurysm (CA),
which contribute to progressive dilation of vascular wall. However, mRNA and
protein expression of local rennin-angiotensin system (RAS) components are found
down-regulated in CA walls, which is contrary to long-holding concept that local
RAS will be activated in response to increased hemodynamic stress and contributes
to thickening of arterial wall. Similarly, MMPs inhibition by doxycycline
effectively ameliorate AAA expansion in basic and clinical researches, but can
not reduce the incidence of CA formation in rat. These evidences may suggest that
suppression of RAS favors the regression of AAA, but at an increased risk of CA
rupture. As the strategies of RAS blockade have became the optimal
antihypertensive drugs of choice in clinical arena, the discrepant responses to
pharmacologic intervention of AAA and CA should be received considerable
attentions, due to their high prevalence in hypertensive population. Here we
proposed that AAA and CA, outward remodeling of elastic and muscular arteries
respectively, presented with different pathological evolutions and distinct
responses to drug intervention, i.e., RAS and MMPs inhibition. It can not be
excluded that the potentially deleterious effects of RAS inhibition on CA may be
masked by the beneficial action of controlled blood pressure, and the propagation
of CA will be exacerbated once suboptimal dose have been prescribed, or under the
condition of stress, even drug withdrawal. If the paradoxical outcomes of these
two kinds of arterial remodeling were proven true in basic research, clinical use
of RAS blockade should be prudent in hypertensive patients, and routine
procedures to detect the existence of CA should be considered. Therefore, in
depth investigation in their responses to pharmacological approaches will provide
us with more insights into the pathogenesis of arterial aneurysm.
PMID- 17030101
TI - Development of a PCR to diagnose BLV genome in frozen semen samples.
AB - The sanitary and economic impact of BLV infection is associated with the
interference in the international movement of cattle and their germ plasm.
Although experimental data support the improbability that semen from BLV-positive
bulls could infect recipient cows, restriction for commercialization of semen
from infected animals is still present. The objective of this work was to
standardize a PCR assay to diagnose the presence of BLV genome in frozen semen
samples. The developed methodology involves the amplification of an internal
fragment of gag gene. The limit of detection of this technique was six viral
particles, using gag-PCR followed by hybridization analysis. Frozen semen samples
from seropositive bulls were analyzed. It was possible to detect proviral DNA in
9 out of 173 samples. Additionally, a biological test in susceptible sheep was
performed in order to evaluate the transmission of BLV genome by semen from
seropositive animals. This data strongly suggest that semen from seropositive
bulls that resulted negative by PCR can be used for artificial insemination (AI),
accompanied by proper collection protocols. The development of this PCR assay
constitutes a valuable diagnostic tool to determine the BLV-free status of frozen
semen samples used for AI.
PMID- 17030102
TI - Isoniazid-induced hepatotoxicity in rat hepatocytes of gel entrapment culture.
AB - Gel entrapment culture of rat hepatocytes in hollow fibers were evaluated as a
potential in vitro model for studies on isoniazid-induced hepatotoxicity. After
exposure to isoniazid (0.11 mM and 1.1 mM) for 24-96 h, gel entrapped hepatocytes
were more severely damaged than hepatocyte monolayers according to the assays on
methyl thiazolyl tetrazolium (MTT) reduction, intracellular glutathione (GSH)
content, reactive oxygen species (ROS) levels, and albumin secretion.
Furthermore, CYP 2E1 activity detected by 4-nitrocatechol (4-NC) formation
maintained at least 7 days in gel entrapped hepatocytes but decreased to an
undetectable level within 2 days in hepatocyte monolayer. And the addition of CYP
2E1 inhibitor, diethyl-dithiocarbamate (DDC), significantly reduced isoniazid
induced GSH depletion in gel entrapped hepatocytes. In addition, the protective
effects of N-acetylcysteine (NAC), GSH, liquorice extract and glycyrrhizic acid
(GA), a purified compound from liquorice extract, against isoniazid
hepatotoxicity were clearly observed in gel entrapped hepatocytes at 72 h
incubation. Overall, gel entrapped hepatocytes were more susceptible to isoniazid
induced hepatotoxicity than hepatocyte monolayers by a possible mechanism that
higher CYP 2E1 activity in gel entrapped hepatocytes could enhance isoniazid
toxicity. This indicates that gel entrapped hepatocytes in hollow fibers could be
a more effective model than hepatocyte monolayer for hepatotoxicity research in
vitro.
PMID- 17030103
TI - Change in serum undercarboxylated osteocalcin concentration in bilaterally
oophorectomized women.
AB - OBJECTIVE: We investigated changes in serum undercarboxylated osteocalcin (ucOC)
concentrations, bone turnover markers and spine bone mineral density (BMD) in
women who had undergone bilateral oophorectomy during the premenopausal period.
METHODS: The study population comprised 141 bilaterally oophorectomized and 32
premenopausal women for a cross-sectional study. The longitudinal study consisted
of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum
concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase
(BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a
bone resorption marker and serum parathyroid hormone (PTH) concentration were
measured. RESULTS: Serum concentration of ucOC in women at 1 month after
bilateral oophorectomy was significantly (p<0.05) higher than that in
premenopausal women and the high level was sustained after surgical menopause. On
the other hand, serum OC concentration at 1 month after surgical menopause was
not different from that in premenopausal women. In the longitudinal study, serum
ucOC concentration at 1 month after surgical menopause was significantly (p<0.05)
increased compared to that before bilateral oophorectomy, while serum OC
concentrations before and at 1 month after surgical menopause were not
significantly different. CONCLUSION: The results of this study showed that serum
ucOC concentration rapidly increases in women after bilateral oophorectomy and
that change in serum ucOC concentration after surgical menopause is different
from change in serum OC concentration.
PMID- 17030104
TI - Dry eye in post-menopausal women using hormone replacement therapy.
AB - PURPOSE: To evaluate the effect of hormone replacement therapy (HRT) on dry eye
in post-menopausal women. METHODS: Forty post-menopausal women with dry eye (20
patients, group 1) and without dry eye (20 patients, group 2), and planning to
receive HRT (estrogen plus progesterone), were recruited as the study groups.
Forty age-matched untreated women were enrolled as controls (group 3 with dry
eye, 5 patients; group 4 without dry eye, 35 patients). Patients having at least
one of the symptoms (dryness, itching, photophobia, foreign body sensation, and
tearing) together with two of the tests with positive results for dry eye (tear
film break-up time (BUT), fluorescein staining of the cornea, analysis of the
meibomian gland, and Schirmer I test) in both eyes were considered dry eye
positive. Hormonal assay for follicle stimulating hormone, luteinizing hormone,
estradiol, and free testosterone was performed. Dry eye statuses in the groups
were evaluated statistically. RESULTS: Four patients with incomplete follow-up
data were excluded. HRT use increased estradiol levels in the groups. Mean ages
of patients (50.2+/-4.8 and 50.7+/-3.9 years, and 50.0+/-4.6 and 53.0+/-3.9
years) were similar (p=0.67). Duration of menopause in groups 1 and 2 (3.2+/-2.2
and 1.4+/-1.2 years; p=0.01), and in groups 3 and 4 (3.0+/-1.6 and 1.7+/-1.3
years; p=0.014) were different. At the third month examinations, all of the
patients in group 1, and 11 patients (61.1%) in group 2 had dry eye (p=0.003).
CONCLUSION: Duration of menopause and use of HRT may increase the incidence of
dry eye in post-menopausal woman.
PMID- 17030105
TI - Essential oil of Pterodon polygalaeflorus inhibits electromechanical coupling on
rat isolated trachea.
AB - The present work studied the effects of the essential oil of Pterodon
polygalaeflorus (EOPP), a plant used to treat bronchitis and amigdalytis, on rat
airway smooth muscle in vitro. In Ca(2+)-containing medium, EOPP (100-1300
microg/ml) inhibited preferentially high KCl- than 5-HT-induced muscle
contractions in a concentration-dependent fashion, but did affect neither basal
muscle tension nor ACh-induced contractions. In preparations maintained in either
60 mM K(+) or 10 microM ACh in Ca(2+)-free medium, EOPP (100, 600 and 1300
microg/ml) inhibited maximum contractile response induced by cumulative Ca(2+)
addition (0.1-20 mM). Verapamil (10, 30 and 100 microg/ml), a Ca(2+) channel
blocker, also inhibited Ca(2+)-induced concentration-effect curve in presence of
ACh in Ca(2+)-free medium, whilst it was ineffective to decrease cholinergic
contractions in Ca(2+)-containing medium. In presence of 150 mM K(+) in Ca(2+)
containing medium, EOPP (1300 microg/ml) did not reversed ACh-induced
contractions. In contrast, under similar conditions, EOPP almost fully relaxed
cholinergic contractions of tracheal smooth muscle in Ba(2+)-containing medium.
In medium containing 10 mM tetraethylammonium and 2 mM Ba(2+) instead of Ca(2+),
both EOPP (1300 microg/ml) and verapamil (approximately 5 microg/ml)
significantly decreased ACh-induced contractions. Thus, in rat isolated trachea,
EOPP induces inhibitor effects on contractions preferentially triggered by an
electromechanical coupling mode.
PMID- 17030106
TI - Further evidence of in vitro production of gamma-hydroxybutyrate (GHB) in urine
samples.
AB - This study was designed to supplement previous studies that documented in vitro
production of gamma-hydroxybutyrate (GHB) in urine samples. Urine samples were
provided by subjects who reported that they had never used GHB (n=31). The
specimens were stored under standard conditions of refrigeration (5 degrees C)
without any preservatives added. All specimens were repeatedly analyzed for the
presence of endogenous GHB over a 6-month period using a previously reported
headspace GC-MS method. Significant elevations in GHB were observed in many of
the urine samples as storage time increased. As a result, the in vitro production
of GHB may increase the apparent GHB concentrations in urine during storage. This
potential for an artificial increase in GHB concentration must be appreciated
when establishing the threshold between endogenous and exogenous concentrations
of GHB.
PMID- 17030107
TI - Zinc-binding proteins (metallothionein and alpha-2 macroglobulin) and
immunosenescence.
AB - Zinc is a relevant trace element for the efficiency of the entire immune system.
The binding of zinc with some proteins, such as metallothioneins (MT) and alpha-2
macroglobulin (alpha-2M) is crucial for the immune efficiency during ageing and
in age-related diseases, because these proteins may be involved in antagonistic
pleiotropic effects. Indeed, the presence of chronic inflammation during ageing,
generally, induces overexpression of these proteins that, due to their original
biological function in fighting stressor agents, continuously sequester
intracellular zinc. As a consequence, a low zinc ion availability may appear in
aged organisms leading to impairments of the immune response at thymic and
extrathymic levels with the risk of the appearance of age-related diseases.
Therefore, MT and alpha-2M turn from protective in "young-adult age" to harmful
agents in "ageing" following the basic assumption of an evolutionary theory of
ageing, named the "antagonistic pleiotropy", which suggests that a trade off
between early beneficial effects and late negative outcomes can occur at a
genetic and molecular level. On the other hand, some polymorphisms of MT (MT2A)
and alpha-2M have been associated with atherosclerosis or Alzheimer disease,
respectively. Physiological zinc supplementation in elderly restores the thymic
endocrine activity and innate immune response (NK cell cytotoxicity) and
increases the survival rate in old mice. Therefore, zinc supplementation is
useful to achieve health longevity because these zinc-binding proteins may regain
their original protective task against oxidative damage with, thus, a beneficial
impact on immune response.
PMID- 17030108
TI - Influence of mammographic density on the diagnostic accuracy of tumor size
assessment and association with breast cancer tumor characteristics.
AB - PURPOSE: The accuracy of breast cancer staging involves the estimation of the
tumor size for the initial decision-making in the treatment. We investigated the
accuracy of tumor size estimation and the association between tumor
characteristics and breast density (BD). MATERIALS AND METHODS: A total of 434
women with a primary diagnosis of breast cancer were included in this prospective
study at a specialist breast unit. Estimated tumor characteristics included tumor
size, nodal status, estrogen/progesterone receptor status, Ki-67, HER2/neu,
vascular invasion. Radiomorphological data included tumor size as assessed by
mammography, breast ultrasonography, and clinical examination, and American
College of Radiology (ACR) categories for BD. RESULTS: BD did not have a
significant impact on the assessment of tumor size using breast ultrasound
(deviation from ACR categories 1-4: 0.55-0.68 cm; P=0.331). The deviation in
mammography was significantly different dependent on BD (0.42-0.9 cm; P<0.001).
The clinical examination was not affected by BD. Age and tumor size were the only
parameters associated with a denser breast in the multivariate analysis. Older
women were less likely to have dense breasts (odds ratio 0.157 for women aged
>or=70 years), and patients with larger tumors were less likely to have dense
breasts (adjusted OR 0.36 for tumors>2 cm). CONCLUSION: Breast ultrasonography is
more accurate than mammography for assessing tumor size in breasts with a higher
BD. The difference in tumor size assessment needs to be taken into consideration
in the design of clinical trials and treatment decisions.
PMID- 17030109
TI - HPLC-NMR with severe column overloading: fast-track metabolite identification in
urine and bile samples from rat and dog treated with [14C]-ZD6126.
AB - The subject of this study was the determination of the major urinary and biliary
metabolites of [(14)C]-ZD6126 following i.v. administration to female and male
bile duct cannulated rats at 10 mg/kg and 20 mg/kg, respectively, and male bile
duct cannulated dogs at 6 mg/kg by HPLC-NMR spectroscopy. ZD6126 is a
phosphorylated pro-drug, which is rapidly hydrolysed to the active metabolite,
ZD6126 phenol. The results presented here demonstrate that [(14)C]-ZD6126 phenol
is subsequently metabolised extensively by male dogs and both, male and female
rats. Recovery of the dose in bile and urine was determined utilising the
radiolabel, revealing biliary excretion as the major route of excretion (93%) in
dog, with the majority of the radioactivity recovered in both biofluids in the
first 6 h. In the rat, greater than 92% recovery was obtained within the first 24
h. The major route of excretion was via the bile 51-93% within the first 12 h.
The administered phosphorylated pro-drug was not observed in any of the excreta
samples. Metabolite profiles of bile and urine samples were determined by high
performance liquid chromatography with radiochemical detection (HPLC-RAD), which
revealed a number of radiolabelled components in each of the biofluids. The
individual metabolites were subsequently identified by HPLC-NMR spectroscopy and
HPLC-MS. In the male dog, the major component in urine and bile was the [(14)C]
ZD6126 phenol glucuronide, which accounted for 3% and 77% of the dose,
respectively. [(14)C]-ZD6126 phenol was observed in urine at 1% of dose, but was
not observed in bile. A sulphate conjugate of demethylated [(14)C]-ZD6126 phenol
was identified in bile by HPLC-NMR and confirmed by HPLC-MS. In the rat, the bile
contained two major radiolabelled components. One was identified as the [(14)C]
ZD6126 phenol glucuronide, the other as a glucuronide conjugate of demethylated
[(14)C]-ZD6126 phenol. However, a marked difference in the proportions of these
two components was observed between male and female rats, either due to a sex
difference in metabolism or a difference in dose level. The glucuronide conjugate
of the demethylated [(14)C]-ZD6126 phenol was present at higher concentration in
the bile of male rats (4-34%), while the phenol glucuronide was present at higher
concentration in the bile of female rats (8-70%) over a 0-6 h collection period.
A third component was only observed in the bile samples (0-6 h and 6-12 h) of
male rats. This was identified as being the same sulphate conjugate of
demethylated [(14)C]-ZD6126 phenol as the one observed in dog bile. The rat
urines contained two main metabolites in greatly varying concentrations, namely
the demethylated [(14)C]-ZD6126 phenol glucuronide and the glucuronide of [(14)C]
ZD6126 phenol. Again, the differences in relative amounts between male and female
rats were observed, the major metabolite in the urines from male rats being the
demethylated [(14)C]-ZD6126 phenol (0-17% in 0-24 h), whilst the phenol
glucuronide, accounting for 0.5-50% of the dose over 0-24 h, was the major
metabolite in females. Methanolic extracts of the pooled biofluid samples were
submitted for HPLC-NMR for the quick identification of the major metabolites.
Following a single injection of the equivalent of 6-28 ml of the biofluids
directly onto the HPLC-column with minimal sample preparation, the metabolites
could be largely successfully isolated. Despite severe column overloading, the
major metabolites of [(14)C]-ZD6126 could be positively identified, and the
results are presented in this paper.
PMID- 17030110
TI - Thyroid hormone deficiency changes the distribution of oligodendrocyte/myelin
markers during oligodendroglial differentiation in vitro.
AB - Myelination depends on the proper differentiation of oligodendrocytes and several
factors may influence this event. For instance, thyroid hormone (T3) affects the
timing of differentiation and regulates the expression of several enzymes
involved in the synthesis of complex lipids and in the expression of some myelin
structural proteins. We investigated the effect of T3 deficiency on
oligodendroglial differentiation and in the distribution of
oligodendrocyte/myelin proteins 2'3'-cyclic nucleotide 3'-phosphodiesterase
(CNPase) and myelin basic protein (MBP). Oligodendroglial-enriched cultures were
obtained from cerebra of neonate rats grown in a modified medium. The T3
deficient status was induced by using medium devoid of T3. We observed a delay,
in T3-deficient cultures, in oligodendroglial maturation characterized by less
extensive processes and membrane vellum than in controls. In control cultures,
CNPase immunoreactivity was punctated, showing cell bodies and processes at
earlier stages and redistribution to cytoskeleton vein-like structures in later
stages. In T3-deficient cultures, CNPase remained in a punctated pattern and only
at 10 days in vitro we observed CNPase redistribution to the presumptive
cytoskeleton vein-like structures. MBP in control cultures was distributed
through the whole cell body and processes whereas in T3-deficient cultures, MBP
immunoreactivity was concentrated in the perinuclear region. These results
reinforce the hypothesis that T3 is an important factor in oligodendrocyte
differentiation, particularly regarding the distribution of myelin proteins.
PMID- 17030111
TI - Cognitive function in adults with type 2 diabetes and major depression.
AB - The aim of this study was to identify characteristics of neuropsychological
functioning among type 2 diabetic adults with and without major depression.
Twenty type 2 diabetics with major depression, 20 non-depressed type 2 diabetics
and 34 controls without diabetes or depression were compared. A mixed effects
repeated measures analysis of covariance indicated significant differences in
overall cognitive functioning between diagnostic groups, specifically depressed
diabetics demonstrated greater cognitive dysfunction than controls. Further
comparisons indicated that depressed diabetics performed significantly worse than
non-depressed diabetics in attention/information processing speed. Relative to
controls, depressed diabetics performed significantly worse in
attention/information processing speed and executive functioning, while there was
a trend for non-depressed diabetics to perform worse in executive functioning.
These findings suggest that depression negatively impacts cognitive performance
among adults with type 2 diabetes, which may have implications for neural
circuitry underlying cognitive and mood changes in diabetic patients.
PMID- 17030112
TI - Comparative proteomic profiles and the potential markers between Burkholderia
pseudomallei and Burkholderia thailandensis.
AB - Burkholderia pseudomallei is a bacterial pathogen causing the melioidosis
disease, which is predominantly found in tropical areas of Southeast Asia and
Northern Australia. Burkholderia thailandensis is a closely related species to B.
pseudomallei but it is non-pathogenic species. In this study, we have constructed
a proteome reference map of B. pseudomallei at the stationary phase of growth by
using two-dimensional gel electrophoresis with a pH 4-7 immobilized pH gradient
combined with matrix-assisted laser desorption ionization time of flight mass
spectrometry. Approximately 550 spots could be detected by Coomassie brilliant
blue G-250 staining, and 88 spots representing 77 unique proteins were
identified. Eleven of the gene products were found in multiple spots indicating
as isoforms. In attempt to detect distinctive expressed proteins between a
virulent and a non-virulent species, the use of comparative proteomic profiles
under the same condition were performed. We could identify more than 20 different
spots. Twelve out of 14 spots are detected in B. pseudomallei and six proteins
have been identified and indicated that they are involved in virulent characters
of bacteria. Two hypothetical proteins were expressed and found only in B.
pseudomallei. These proteins are potential markers to distinguish between these
two species. Our study also provides a useful information of global intracellular
protein expression and is a valuable starting point for analyzing a proteomic
pathogenicity of the bacterial pathogen.
PMID- 17030113
TI - Muscadine grape products intake, diet and blood constituents of non-diabetic and
type 2 diabetic subjects.
AB - OBJECTIVE: Red wines and grape juices contain polyphenolics with antioxidant and
antiplatelet properties that may be protective against oxidative stress leading
to hypertension, insulin resistance, and type 2 diabetes (T2D). This study
evaluated the effects of supplementing meals of subjects with 150 mL of muscadine
grape juice (MJ), muscadine grape wine (MW), and dealcoholized muscadine grape
wine (Dz-W) on glycemic indices, blood constituents, lipid profile,
anthropometric, and nutrient intakes of healthy and T2D subjects over a 28-d
period. METHODS: Subjects with T2D were assigned to take MJ, MW, or Dz-W. Non
diabetics consumed MJ and controls were given no test drinks. Several metabolic
indicators associated with diabetic conditions were measured at baseline and
repeated after 28 d. RESULTS: Diabetics given MW and Dz-W showed lower levels of
blood glucose, insulin, and glycated hemoglobin, indicating better glycemic
control. Elevated dietary vitamin C and E levels were observed in diabetics given
Dz-W, indicating improved antioxidant status. Decreased red blood cell membrane
saturated fatty acids and increased mono- and polyunsaturated fatty acids for
subjects with T2D given MW suggested improved membrane fluidity. Lower sodium and
chloride values for subjects T2D given MW suggested lower risk for developing
hypertension. Improved hepatic conditions were noted by decreases in alanine
aminotransferase and aspartate aminotransferase among subjects with T2D given MW,
indicating better insulin sensitivity and decreased tendency toward impaired
liver function. CONCLUSION: Daily intake of 150 mL of MW or Dz-W with meals
improved several metabolic responses among diabetics compared with diabetics
given MJ.
PMID- 17030115
TI - Effects of constitutive deletion of opioid receptors on the basal densities of
Fas and Fas-associated protein with death domain (FADD) in the mouse brain: a
delta-opioid tone inhibits FADD.
AB - The acute effects of opiate drugs and opiate addiction have been associated with
modulation of Fas/FADD (Fas-Associated protein with Death Domain) signaling
complex in the rat brain. This study investigated the possible existence of
endogenous opioid tones regulating the basal activities of Fas receptor forms and
FADD in the brain, using gene-targeted mice lacking mu-, delta- or kappa-opioid
peptide receptors (KO mice). In mu-KO mice, but not in delta- or kappa-KO mice,
the basal immunodensity of native Fas (35 kDa monomeric form) was decreased in
the cerebral cortex (33%) when compared with WT littermates. In delta-KO mice,
but not in mu- or kappa-KO mice, the basal content of 120 kDa Fas aggregates
(complexes of monomers relevant in Fas signaling) was markedly increased in the
cortex (93%). In contrast, no differences between genotypes were observed in the
basal expression of glycosylated Fas (51/48/45 kDa forms). Notably, the basal
content of FADD (the adaptor protein that couples Fas to caspases and transmits
the death signal) was increased in the cerebral cortex of delta-KO mice (48%),
but not in mu- or kappa-KO mice. In addition, the basal content of phosphorylated
FADD at Ser191 (the relevant species of FADD implicated in nonapoptotic signals)
was also upregulated in the cortices of delta-opioid receptor KO mice (6.5-11.0
fold). The results suggest that mu-receptors tonically stimulate (through
endogenous opioid peptides) the activation of native Fas, whereas delta-receptors
tonically inhibit the expression of Fas aggregates and that of FADD and
phosphorylated FADD (Ser191) in the mouse brain. These data are in line with the
acute opposite modulation of Fas and FADD induced by mu- and delta-opiate
agonists, and strongly support the notion of an anti-apoptotic delta-opioid tone
that restrains Fas signaling.
PMID- 17030114
TI - Effect of calcium fortified milk supplementation with or without vitamin K on
biochemical markers of bone turnover in premenopausal women.
AB - OBJECTIVE: We compared the effect of supplementation with a fortified skimmed
milk product (high calcium skim milk) with or without added phylloquinone
(vitamin K(1)) on markers of bone formation and resorption in premenopausal
women. METHODS: Eighty-two women 20 to 35 y of age were randomly allocated to
three groups. Two groups received two daily servings of high calcium skim milk
(1000 mg/d of extra calcium) with or without added phylloquinone (80 microg/d)
for 16 wk, and a third control group received no supplementation. Bone density
was assessed at baseline and the bone markers, total osteocalcin, type I N
terminal procollagen peptide, and cross-linked C-telopeptide of type I collagen
were measured at baseline and at weeks 2, 12, and 16. Serum phylloquinone and
undercarboxylated osteocalcin were measured in the control and vitamin K
supplemented groups at weeks 0 and 16. RESULTS: Baseline values for age, body
mass index, and bone density did not differ across groups. In vitamin K
supplemented women, mean serum phylloquinone concentrations increased from 0.27
to 0.76 microg/L (P < 0.05) and undercarboxylated osteocalcin concentrations
decreased from 9.68 to 4.46 microg/L (P < 0.05) over 16 wk. Plasma cross-linked C
telopeptide of type I collagen, total osteocalcin, and type I N-terminal
procollagen peptide levels decreased significantly in both supplemented groups
compared with the control group over 16 wk (cross-linked C-telopeptide of type I
collagen >30%, total osteocalcin and type I N-terminal procollagen peptide >15%).
CONCLUSION: Fortified milk supplementation in premenopausal women reduced bone
turnover significantly. Phylloquinone fortification substantially improved
vitamin K status but had no demonstrable additive effect on bone turnover in this
short-term study.
PMID- 17030116
TI - Determinative role of Wnt signals in dorsal iris-derived lens regeneration in
newt eye.
AB - We have previously shown that lens regeneration from the pigmented epithelium of
the dorsal iris in the adult newt eye proceeds in two steps after lens removal or
intraocular FGF2 injection. The FGF2-dependent proliferation of iris pigmented
epithelium and activation of early lens genes that occur over the entire
circumference of the iris comprise the first step, while subsequent dorsally
confined lens development marks the second step. Here, we investigated the
expression of Wnt and Wnt receptor Frizzled genes in lens-regenerating iris
tissues. Wnt2b and Frizzled4 were activated only in the dorsal half of the iris
in synchrony with the occurrence of the second step, whereas Wnt5a and Frizzled2
were activated in both halves throughout the period of the first and second
steps. Cultured explants of the iris-derived pigmented epithelium in the presence
of FGF2 underwent dorsal-specific lens development fully recapitulating the in
vivo lens regeneration process. Under these conditions, Wnt inhibitors Dkk1,
which specifically inhibits the canonical signal pathway, and/or sFRP1 repressed
the lens development, while exogenous Wnt3a, which generally activates the
canonical pathway like Wnt2b, stimulated lens development from the dorsal iris
epithelium and even caused lens development from the ventral iris epithelium,
albeit at a reduced rate. Wnt5a did not elicit lens development from the ventral
epithelium. These observations indicate that dorsal-specific activation of Wnt2b
determines the dorsally limited development of lens from the iris pigmented
epithelium.
PMID- 17030117
TI - Amygdala activation in the processing of neutral faces in social anxiety
disorder: is neutral really neutral?
AB - Previous research has suggested that Social Anxiety Disorder (SAD) is associated
with a tendency to interpret ambiguous social stimuli in a threatening manner.
The present study used event-related functional magnetic resonance imaging to
examine patterns of neural activation in response to the processing of neutral
facial expressions in individuals diagnosed with SAD and healthy controls (CTLs).
The SAD participants exhibited a different pattern of amygdala activation in
response to neutral faces than did the CTL participants, suggesting a neural
basis for the biased processing of ambiguous social information in SAD
individuals.
PMID- 17030118
TI - Irinotecan drug eluting beads for use in chemoembolization: in vitro and in vivo
evaluation of drug release properties.
AB - Drug eluting beads that release irinotecan in a controlled manner may be useful
for application in the chemoembolization of colorectal cancer metastases to the
liver. In this study, irinotecan drug eluting beads were prepared with loadings
up to 50 mg drug/mL hydrated beads. Drug loading was via an ion-exchange
mechanism with sulfonate binding sites in the bead. Release in vitro was shown to
be sustained and dependent upon the presence of ions in the elution medium, drug
loading and bead size. Drug elution in PBS was controlled by solute diffusion
within the beads and gave rise to values for the diffusion coefficient, D, of
between 2.4x10(-9) and 1.4x10(-7) cm(2)s(-1). The beads were shown to decrease in
size (by a maximum 25-30%), and concomitantly their modulus of compression
increased (from approximately 27 kPa to a maximum of about 49 kPa), with
increasing drug loading. This did not however, influence their ability to be
suspended homogeneously in contrast agent or delivered through a microcatheter.
Following porcine hepatic artery embolization, maximum plasma levels were 70-75%
lower for both irinotecan and SN-38 compared to intraarterial bolus
administration, with peak levels observed at 2 and 5 min after completion of the
embolization procedure. The in vivo data were shown to correlate well with the in
vitro release measured using a T-apparatus model of embolization.
PMID- 17030119
TI - [Campylobacter jejuni and cytomegalovirus (CMV) infections in patients with the
Guillain-Barre syndrome].
AB - Guillain-Barre syndrome (GBS) is a rare disease triggered by postinfectious
mechanisms. The disease concerns all ages, and is widely distributed around the
world. The principal risks are respiratory failure, especially during the initial
phase of the disease, and persisting deficit at long term. Among the infectious
known agents, Campylobacter jejuni and CMV represent more than 40% of GBS causes.
The clinical presentation, and the long-term prognosis of GBS related to these
two etiologies are different. The physiopathological mechanisms of the nervous
attack are probably also different. There is no proof, at this time, that anti
infectious treatment can improve the prognosis. The treatment is based on the
early use of immunomodulatory treatments like intravenous immunoglobulins or
plasma exchanges.
PMID- 17030120
TI - [A move meat beginning...and evolutive].
AB - Food allergies are more and more numerous, and frequent in children at all ages.
At any moment, a clinical manifestation, quickly evolutive and alarming, must
need the help call at phone 15, and the intervention of a medical team of SMUR.
The departmental, free, cell to 15 for all medical emergencies note a regular
increase of these specific calls since ten years, as this following case report
shows it.
PMID- 17030121
TI - [Non IgE-mediated cow's milk allergy].
PMID- 17030122
TI - Development of the neural crest: achieving specificity in regulatory pathways.
AB - Recent studies have revealed the signaling pathways and downstream effectors
involved in the specification of the neural crest. Neural crest cells are
generated from a zone at the neurectoderm border in response to Wnt and BMP
signals. BMP signals are involved in establishing a competency zone at the border
of the neurectoderm, while subsequent Wnt signals specify neural crest cells.
Combinations of transcription factors, including pax and msx gene products, act
downstream of these pathways to integrate signals and establish the neural crest.
Mechanisms are emerging for how specificity is generated from reiterated signals
and effectors.
PMID- 17030123
TI - Mitotic phosphatases: no longer silent partners.
AB - Recent work has highlighted the important role played by protein phosphatase
complexes in the regulation of mitosis from yeast to mammals. There have been
important advances in defining the roles of the protein serine/threonine
phosphatases PP1 and PP2A and the dual specificity protein tyrosine phosphatases
CDC25 and Cdc14. Three independent studies defined a regulatory role for PP2A in
the control of sister chromatid cohesion, involving a direct interaction with
shugoshin. A chromatin targeting subunit has been identified for PP1 and the
complex shown to play an essential role in chromosome segregation. Key regulatory
residues within CDC25 have been mapped and its activity tied both to the initial
activation of cyclin-dependent kinases at the centrosome and to DNA damage
checkpoints. Novel roles have been defined for Cdc14, including regulation of
rDNA and telomere segregation and participation in spindle assembly. These
exciting advances show that protein phosphatases are not merely silent partners
to kinases in regulating the control of cell division.
PMID- 17030125
TI - An objective method for regularization of fiber orientation distributions derived
from diffusion-weighted MRI.
AB - Spherical deconvolution is an elegant method by which the orientation of crossing
fibers in the brain can be estimated from a diffusion-weighted MRI measurement.
However, higher resolution of fiber directions comes at the cost of higher
susceptibility to noise. In this study, we describe the use of linear
regularization of the fiber orientation distribution function by Damped Singular
Value Decomposition. Furthermore, the degree of regularization is optimized on a
voxel-by-voxel basis with no user interaction using Generalized Cross Validation.
We find, by simulations, that regularization can improve the reliability of fiber
orientation determination when the signal-to-noise ratio is low. Simulations and
in vivo measurements indicate that spurious peaks of the fiber orientation
distribution function in regions with low anisotropy largely disappear when
regularization is introduced. The methods examined are fast enough to be used on
a routine basis with diffusion MRI data sets and may improve estimation of water
diffusion properties in heterogeneous white matter and boost reliability of fiber
tracking through regions of brain with complex fiber geometry.
PMID- 17030124
TI - Sonic hedgehog signaling in forebrain development and its interactions with
pathways that modify its effects.
AB - During the development of the nervous system and other organs in the embryo, a
limited set of master signaling pathways are used repeatedly for induction,
patterning and growth. Among these, the Sonic hedgehog (Shh) pathway is crucial
for the development of many structures in the brain. How the context-specific
interplay between these various signaling pathways produces distinct temporal and
spatial outcomes is not clear. Resolving this problem is a major goal in the
study of cell and organ development. Here, we focus on signaling events during
dorso-ventral patterning of the embryonic forebrain in vertebrates. In
particular, we discuss the role of the Shh pathway in this process and on its
interactions with the FGF, retinoic acid and Nodal pathways and other information
cascades that modify its effects.
PMID- 17030126
TI - Subacromial plica as a cause of impingement in the shoulder.
AB - The subacromial bursa is the largest bursa in the body. In 1934, Codman described
the presence of subacromial plicae, similar to the suprapatellar plicae found in
the knee. It is recognized that plicae in the knee can cause anterior knee pain
with impingement against the patella in young persons. We investigated the
possibility that a similar situation exists with plicae of the subacromial bursa.
The aims of this study were to document the prevalence of bursal plicae seen at
bursoscopy during arthroscopic subacromial decompression of the shoulder and to
assess whether there is any pattern in the occurrence of these plicae, as well as
the relationship to impingement lesions seen at bursoscopy. Between January 1996
and July 2001, all cases undergoing arthroscopic decompression were evaluated for
anatomic-pathologic changes of the subacromial bursa, including the presence of
plicae and impingement lesions. A total of 1732 cases complying with inclusion
criteria were recorded, with plicae observed in 104 (6.0%). The occurrence of
plicae showed a highly significant younger age predilection (P = .0008, chi(2)
test) but no differences between sexes or sides. The occurrence of subacromial
plicae was highly associated with the combined severity of the impingement lesion
on the acromial and bursal side. Plicae were most common in shoulders showing an
impingement lesion on the cuff bursal side, with no impingement lesion on the
acromial side. The odds of the impingement lesion being milder on the acromial
side was 3.41 times higher in shoulders with a plica compared with shoulders
without a plica. This suggests that impingement of the cuff may be due to the
plica itself. This study is the first to describe the presence of subacromial
plicae in living subjects and correlates with previous anatomic studies. The
younger age predominance correlates with the findings of plicae in the knee. Our
findings suggest that subacromial plicae may be a cause of impingement in young
patients.
PMID- 17030127
TI - Irreducible pulled elbow in an adult: a case report.
PMID- 17030128
TI - The effect of total shoulder arthroplasty on self-assessed deficits in shoulder
function in patients with capsulorrhaphy arthropathy.
AB - The objective of this study was to characterize self-assessed functional deficits
before and after total shoulder arthroplasty (TSA) in a consecutive series of 24
patients treated for capsulorrhaphy arthropathy. Deficits were determined by use
of the Simple Shoulder Test. The effects of age, type of original stabilization
surgery, duration of time since the initial repair, and pattern of glenoid
erosion were analyzed. Deficits were significantly reduced from 8.5 to 4 of 12
SST items after TSA (P = .003). Items related to motion and function had the
largest effect on improvement. Age did not affect results. There was a trend
toward greater improvement in patients whose original stabilization was less than
20 years previously (P = .06) and in those with concentric glenoid erosion (P =
.06). A prior Bristow procedure was associated with the least improvement.
Overall, TSA was an effective treatment for capsulorrhaphy arthropathy at midterm
follow-up. Restoring range of motion appears to have the largest impact on
improvement in function.
PMID- 17030129
TI - Treatment of ligament laxity by electrothermal shrinkage or surgical plication: a
morphologic and mechanical comparison.
AB - Capsular plication or thermal shrinkage can be used to enhance surgical joint
stabilization. We compared mechanical or morphologic properties of the medial
collateral ligament of the rabbit knee treated by either bipolar radiofrequency
electrothermal shrinkage or surgical plication. After 12 weeks, the medial
collateral ligaments were procured from treated and contralateral knees to
undergo viscoelastic (creep) testing, quantitative transmission electron
microscopy, and immunohistochemistry. Creep strain in thermal (1.85% +/- 0.32%)
and plicated (1.92% +/- 0.36%) ligaments was almost twice that of the control
group (1.04% +/- 0.15%), although there was no difference between treatment
modalities. The morphologic parameters of all 3 groups were significantly
different (P < .001). The thermal ligaments demonstrated predominantly small
fibrils, whereas the plicated group displayed an intermediate distribution of
heterogeneous fibrils, suggesting a different pattern of remodeling. Viscoelastic
properties are similar after thermal shrinkage or plication, though inferior to
those of intact ligaments.
PMID- 17030130
TI - Pre-operative radial arterial diameter predicts early failure of arteriovenous
fistula (AVF) for haemodialysis.
AB - INTRODUCTION: Long term patency of arteriovenous fistula (AVF) is relevant to the
management of end stage renal failure (ESRF) patients on haemodialysis (HD). We
evaluated the role of routine radial arterial duplex for imaging radial artery
before AVF formation to investigate the relationaship between radial artery
internal diameter (ID) and AVF patency. METHODS: 21 patients with ESRF were
examined by duplex sonography before AVF formation, 1 day, 1 week, 4 week and 12
weeks post AVF formation. For assessment of AVF patency, patients were divided
into 2 groups. Group-1, 11 patients with radial artery ID <1.5mm and Group-2, 10
patients with radial artery ID >1.5mm. Measurement of radial artery blood inflow
rate was calculated from mean blood flow velocity and vessel diameter. All AVFs
were constructed on the forearm using autologous veins. RESULTS: In Group-1, 5
patients (45%) showed immediate thrombosis of AVF graft. All patients in group-2
had patent AVF at 12 weeks. Pre-AVF formation radial artery blood inflow rate
between two groups was not significantly different (p=0.06). Radial artery blood
inflow rate was consistently and significantly higher in group-2 at all later
time points with p value of <0.01 (Mann Whitney test). CONCLUSION: There was a
high failure rate of AVF with radial artery ID of <1.5mm. In the presence of
small radial arteries primary access AVF in the upper arm should be considered.
PMID- 17030131
TI - Haemodynamic and clinical assessment of lateral marginal vein excision in
patients with a predominantly venous malformation of the lower extremity.
AB - OBJECTIVE: The purpose of the present study was to determine the effects of the
surgical excision of lateral marginal veins (LMVs) in patients with a venous
malformation (VM) affecting the lower extremity. METHODS: Preoperative and
postoperative air plethysmography (APG), CEAP classification C scores, and venous
clinical severity scores (VCSS) of the 25 VM patients who underwent LMV excision
were compared. RESULTS: After LMV excision, venous haemodynamic parameters
revealed significantly increased ejection fraction (EF, 33.2 S.D.18.5% vs. 39.7
S.D.21.2%, P=.020), and reduced venous volume (VV, 235.0 S.D.141.8 ml vs. 198.0
S.D.114.1 ml, P=.016) and residual venous fraction (RVF, 62.4 S.D. 26.6% vs. 56.9
S.D. 25.3%, P=.046). Clinical assessments of affected limbs revealed
significantly improved mean CEAP C scores and VCSS (preoperative score, 4.4
S.D.1.7 vs. postoperative score 2.4 S.D.1.7, P=.026) after LMV excision versus
preoperative data. CONCLUSION: Haemodynamic and clinical improvements were
observed in patients with lower extremity VM after LMV excision.
PMID- 17030132
TI - How accurately can the parameters from a model of anisotropic 3He gas diffusion
in lung acinar airways be estimated? Bayesian view.
AB - In the framework of a recently proposed method for in vivo lung morphometry,
acinar lung airways are considered as a set of randomly oriented cylinders
covered by alveolar sleeves. Diffusion of (3)He in each airway is anisotropic and
can be described by distinct longitudinal and transverse diffusion coefficients.
This macroscopically isotropic but microscopically anisotropic model allows
estimation of these diffusion coefficients from multi b-value MR experiments
despite the airways being too small to be resolved by direct imaging. Herein a
Bayesian approach is used for analyzing the uncertainties in the model parameter
estimates. The approach allows evaluation of relative errors of the parameter
estimates as functions of the "true" values of the parameters, the signal-to
noise ratio, the maximum b-value and the total number of b-values used in the
experiment. For a given set of the "true" diffusion parameters, the uncertainty
in the estimated diffusion coefficients has a minimum as a function of maximum b
value and total number of data points. Choosing the MR pulse sequence parameters
corresponding to this minimum optimizes the diffusion MR experiment and gives the
best possible estimates of the diffusion coefficients. The mathematical approach
presented can be generalized for models containing arbitrary numbers of estimated
parameters.
PMID- 17030133
TI - The influence of nitrogen-15 proton-driven spin diffusion on the measurement of
nitrogen-15 longitudinal relaxation times.
AB - The effect of nitrogen-15 proton-driven spin diffusion on quantitative (15)N T(1)
measurements in solid proteins is investigated, and the impact on the measurement
of dynamic parameters is assessed. A simple model of exchange between neighboring
nitrogens is used to reproduce the evolution of (15)N spin systems whose
longitudinal relaxation rates and exchange rates are compatible with experimental
measurements. We show that the induced error in the measured T(1) and its effect
on the determination of dynamics parameters is likely to be less than the current
experimental error. The use of deuterated protein samples is shown to have a
small but sometimes visible effect, and may also considerably slow down or even
suppress the exchange of magnetization due to spin diffusion.
PMID- 17030134
TI - Application of the independent molecule model to elucidate the dynamics of
structure I methane hydrate.
AB - Raman spectroscopy has exhibited the C-H stretch (A1 mode) frequency nu1 of
hydrated methanes at 2915 cm(-1) for the 5(12) cage and 2905 cm(-1) for the
5(12)6(2) cage. These values are lower than the frequency of 2916.5 cm(-1) in
gaseous methane. In this paper, we theoretically examine the Raman spectra
observed in methane hydrate by normal mode analysis using the independent
molecule model. By a breakdown of the symmetry, the four frequencies in modes A1,
E, T2 and T2 observed in gaseous methane are separated into nine frequencies in
the hydrate. It is necessary to consider the anharmonic potential energy within
methane and hydrogen bonding between methane hydrogen and water oxygen in order
to get a result in qualitative agreement with experiment. The frequency in the
5(12)6(2) cage is shifted downward in comparison to the one in 5(12), and the
frequencies in the both cages are also shifted downward compared with the
frequencies in gas. Calculations are also reported for the isotopic methane (CD4,
13CH4) hydrates.
PMID- 17030135
TI - Influence of physical preconditioning on the responsiveness of rat pulmonary
artery after pulmonary ischemia/reperfusion.
AB - The aim of this work was to evaluate the effect of physical preconditioning in
the responsiveness of rat pulmonary rings submitted to lung ischemia/reperfusion
(IR). Wistar rats were divided into three groups: Sedentary sham-operated
(SD/SHAM); sedentary submitted to ischemia/reperfusion (SD/IR) and trained
submitted to ischemia/reperfusion (TR/IR) animals. Exercise training consisted in
sessions of 60 min/day running sessions, 5 days/week for 8 weeks. Left pulmonary
IR was performed by occluding for 90 min and reperfusing for 120 min. After that,
pulmonary arteries were isolated and concentration-response curves to
acetylcholine (ACh), histamine (HIST), sodium nitroprusside (SNP), phenylephrine
and U46619 were obtained. Neither potency (-log EC(50)) nor maximal responses
(E(max)) were modified for ACh and HIST in all groups. On the other hand, the
potency for SNP was significantly increased in TR/IR group (8.23+/-0.06) compared
to SD/IR group (7.85+/-0.04). Contractile responses mediated by a-adrenergic
receptor were markedly decreased in IR groups (SD/IR: 6.75+/-0.06 and TR/IR:
6.62+/-0.04) compared to SD/SHAM (7.33+/-0.05). No changes were seen for the
U46619 in all groups. In conclusion, the present study shows that exercise
training has no protective actions in the local blood vessel where the IR process
takes place.
PMID- 17030136
TI - Maternal diet influences gene expression in intestine of offspring in chicken
(Gallus gallus).
AB - The diet of the mother during pregnancy influences the onset of different
diseases and health-related traits in the offspring. We investigated the
influence of the mother hen diet on the intestinal gene expression pattern in the
offspring. Hens received for 11 weeks either a commercial feed or a commercial
feed supplemented with vitamins and minerals. The offspring of the two groups
showed no changes in growth rate or feed conversion. Of this offspring, gene
expression patterns in the intestine were measured at 3 and 14 days of age with
an intestinal cDNA-microarray. Between the two groups, 11 genes were found to be
differentially expressed both at 3 and 14 days of age. Thus, these genes were
differently regulated when the intestine is developing as well as when the
intestine is more mature. Genes that are differentially expressed at day 3 and/or
day 14 affect intestinal turnover, proliferation and development, metabolism and
feed absorption. To confirm that differences in gene expression are related to
intestinal development, we investigated intestinal proliferation. This indeed
also showed differences in proliferation between the two groups at day 3 and day
14 of age. The gene expression and proliferation results indicate that feed of
the hens influences the functionality of intestine of the offspring at day 3 and
14 of age.
PMID- 17030137
TI - Effect of sudden salinity change on Penaeus latisulcatus Kishinouye
osmoregulation, ionoregulation and condition in inland saline water and potassium
fortified inland saline water.
AB - Two trials were conducted to determine the effect of sudden decrease in salinity
of raw and potassium-fortified inland saline water on western king prawn Penaeus
latisulcatus osmoregulation, ionoregulation and condition. Prawns were subjected
to salinity decrease over 1 h from 32 to 25 ppt in the first trial and from 27 to
20 ppt in the second trial in three water types: inland saline water with
potassium fortified to 100% and 80% of the marine water concentration (IS100,
IS80), and raw inland saline water (ISW). In the first trial condition and
ingestion rate were monitored over 19 days following salinity change. In the
second trial condition, haemolymph osmo- and iono-regulation were recorded over
48 h following salinity change. In the first trial, 100% mortality was observed
in ISW by day 13, with final survival 94% in IS80 and 100% in IS100. Tail muscle
moisture content increased significantly (P < 0.05) over time in both trials and
in all water types, suggesting loss of energy reserves. In the second trial,
serum osmolality, sodium concentration and osmoregulatory capacity decreased
following salinity change, stabilising by 24 h in IS100 and IS80 but continuing
to decrease till 48 h in ISW, suggesting partial breakdown of osmoregulatory
function in the potassium-deficient medium. Prawns were stronger regulators of
divalent than monovalent cations. These trials demonstrate that potassium
deficient inland saline water requires fortification with potassium to allow
prawn survival and efficient osmoregulation.
PMID- 17030138
TI - Muscle delta13C change in Nile tilapia (Oreochromis niloticus) fingerlings fed on
C3-or C4-cycle plants grain-based diets.
AB - The effects of grain-based diets from C3 or C4-cycle plants on muscle delta(13)C
change process in Nile tilapia (Oreochromis niloticus) fingerlings were
investigated. Two groups of sex reversal males Nile tilapia fingerlings were fed
with isoproteic (32.0% DP) and isocaloric (3200 kcal DE/kg) diets, differing from
each other by their delta(13)C. Muscle samples were collected and the carbon
isotopic composition was measured. For C4 diet, the formula for the muscle
delta(13)C change related to the intake time of a new diet was delta(13)C=-14.88
9.21e(-0.0209t) and the half-life (T) of the muscle carbon was 33.2 days. For C3
diet, the formula was delta(13)C=-25.43+8.59e(-0.0533t) with T=13 days. The C3
diet was considered more appropriate based on its palatability and consequent
larger food intake than the C4 diet, resulting in an increased muscle delta(13)C
change rate. However, for future studies, would be necessary to mix both the C3
and C4 feedstuffs to formulate diets nutritionally appropriated, with contrasting
stable isotopes signatures. Tissue delta(13)C change rate is therefore indicated
as a promising tool to better understand the biotic and abiotic factors that
influence nutrients utilization from the diet and animal growth.
PMID- 17030139
TI - Left ventricular myocardal activation under ventricular paced beats in chickens
Gallus gallus domesticus.
AB - The aim of the study was to advance our knowledge regarding the activation
process of the ventricular myocardium in birds in which Purkinje fibres penetrate
into the ventricular wall to reach the epicardium. A depolarization pattern of
the left ventricular free wall was studied in chickens (Gallus gallus) during
ventricular paced beats. Duration of the activation process of the left
ventricular free wall is significantly increased during ventricular ectopic
excitation as compared with sinus rhythm. Its lowest increase occurs during
subendocardial pacing of the middle part of the left ventricle, but its greatest
increase is observed during subepicardial pacing of the left ventricular base.
Multifocality and mosaicity of depolarization of the left ventricular free wall
myocardium in chicken are expressed in a considerably less degree during
ventricular paced beats in comparison with sinus rhythm. During ventricular paced
beats, excitation of the left ventricular free wall is mostly due to the
successive spreading of the depolarization wave from pacing sites.
PMID- 17030140
TI - Effects of GH on immune and endocrine responses of channel catfish challenged
with Edwardsiella ictaluri.
AB - The effects of GH on immune and endocrine responses to channel catfish challenged
with the bacterium Edwardsiella ictaluri were examined. Catfish (11.7+/-1.0 g)
treated with recombinant bovine growth hormone (rbGH) and challenged with E.
ictaluri experienced similar mortality as control-exposed fish. Plasma activity
of lysozyme was higher (P<0.01) in rbGH-exposed fish. Compared to day 0 controls
(non-exposed fish), IGF-I levels decreased (P<0.05) in challenged fish while
levels were similar (P>0.10) between treatments. Abundance of GH receptor (GHR)
mRNA tended to decrease (P=0.055) in liver of challenged fish while toll like
receptor 5 (TLR5) mRNA increased (P<0.05) in liver compared to d 0 controls. An
increase in lysozyme may suggest GH enhances a nonspecific immune response. A
decrease in GHR mRNA and plasma IGF-I suggests a downregulation of the
somatotropic axis in response to disease. The increase in TLR5 mRNA suggests that
TLR5 may play a role in host response to bacterial challenge. While exogenous
rbGH may play a stimulatory role to increase lysozyme levels, there was no
apparent effect of rbGH on mortality to E. ictaluri.
PMID- 17030141
TI - Structural characterization of the lipovitellin from the shrimp Macrobrachium
borellii.
AB - In oviparous species, proteins and lipids are found in the vitellus forming
lipoproteins called lipovitellins. They are an important energy source for
embryos development and larvae growth and survival. We have previously isolated
and partially characterized the sole egg cytosolic lipovitellin from the
freshwater shrimp Macrobrachium borellii. It is a native protein of 440 kDa,
composed of two subunits of 94 and 112 kDa. In the present work we studied size,
shape and structure of M. borellii lipovitellin using electron microscopy,
crosslinking reagents, MALDI-TOF, circular dichroism, fluorescence and partial
proteolysis. The results showed that lipovitellin has a quasi spherical
morphology with an estimated diameter of 18.5+/-3.5 nm. It appears to be composed
of two subunits of 94 kDa, and one of 112 kDa. The larger subunit is more
susceptible to trypsinolysis, indicating that it is less compactly folded and/or
more exposed to the aqueous medium than the 94 kDa subunits. The hetero-trimer is
held together by non-covalent interactions. Peptide mass fingerprinting by MALDI
TOF, produced 42 polypeptides matching to a vitellogenin of a related species
(Macrobrachium rosenbergii). Circular dichroism indicated that this protein
contains 35.7% alpha-helix, 16.6% beta-sheet and 20% turns. Tryptophan
fluorescence emission, at a maximum of 334 nm, indicated that the environment
polarity of these aromatic residues is similar to that of other crustacean
lipoproteins.
PMID- 17030142
TI - A combined study of heat and mass transfer in an infant incubator with an
overhead screen.
AB - The main objective of this study is to investigate the major physical processes
taking place inside an infant incubator, before and after modifications have been
made to its interior chamber. The modification involves the addition of an
overhead screen to decrease radiation heat losses from the infant placed inside
the incubator. The present study investigates the effect of these modifications
on the convective heat flux from the infant's body to the surrounding environment
inside the incubator. A combined analysis of airflow and heat transfer due to
conduction, convection, radiation and evaporation has been performed, in order to
calculate the temperature and velocity fields inside the incubator before and
after the design modification. Due to the geometrical complexity of the model,
computer-aided design (CAD) applications were used to generate a computer-based
model. All numerical calculations have been performed using the commercial
computational fluid dynamics (CFD) package FLUENT, together with in-house
routines used for managing purposes and user-defined functions (UDFs) which
extend the basic solver capabilities. Numerical calculations have been performed
for three different air inlet temperatures: 32, 34 and 36 degrees C. The study
shows a decrease of the radiative and convective heat losses when the overhead
screen is present. The results obtained were numerically verified as well as
compared with results available in the literature from investigations of dry heat
losses from infant manikins.
PMID- 17030144
TI - Engineering novel traits in plants through RNA interference.
AB - RNA interference (RNAi) is a homology-dependent gene silencing technology that
involves double-stranded RNA directed against a target gene or its promoter
region. Using hairpin constructs, double-stranded RNA can be expressed in plants
relatively easily, enabling this technology to be applied to a wide range of
species to silence the expression of both specific endogenous genes and genes of
invading pathogens. RNAi has also been used to engineer metabolic pathways to
overproduce secondary products with health, yield or environmental benefits. The
application of tissue-specific or inducible gene silencing, with the use of
appropriate promoters, and the ability to silence several genes simultaneously
should enhance our ability to create novel traits in plants.
PMID- 17030145
TI - Plant nitric oxide synthase: a never-ending story?
PMID- 17030146
TI - Receptor protein kinases--pattern recognition receptors in plant immunity.
AB - Plant innate immunity is activated either upon perception of pathogen-associated
molecular patterns (PAMPs) by pattern recognition receptors (PRRs) or upon
resistance (R) protein-mediated recognition of pathogen race-specific effector
molecules. Although many plant R proteins have been identified, there is only
limited knowledge about plant PRRs. Recently, Cyril Zipfel et al. identified a
second Arabidopsis leucine-rich repeat receptor protein kinase implicated in PAMP
perception, which suggests that several members of this large protein family
function as pattern recognition receptors.
PMID- 17030147
TI - Auxin and cell polarity: the emergence of AXR4.
AB - Polar localization of the Arabidopsis auxin influx facilitator protein AUX1 in
certain cell types is essential for normal root gravitropism and lateral root
formation. Sunethra Dharmasiri and colleagues recently reported that this polar
localization requires the activity of the AXR4 gene. The sequence of the AXR4
gene suggests that novel mechanisms could be important for targeting certain
proteins to specific cellular locations.
PMID- 17030148
TI - Nickel(II) complexes of biologically active glutathione: spectroscopic, kinetics
of thermal decomposition and XRPD studies.
AB - Nickel(II) complexes of reduced glutathione (GSH) of general composition
Na[Ni(L)(X)]H(2)O, where H(2)L=GSH; X=NO(3)(-), SCN(-), CH(3)CO(2)(-), Cl(-) have
been synthesized and characterized by elemental analysis, infrared spectra,
electronic spectra, magnetic susceptibility measurements, thermal and X-ray
powder diffraction studies. Infrared spectra indicate deprotonation and
coordination of cysteinyl sulphur and carboxylate oxygen of glycine residue with
nickel ions. It indicates the presence of water molecule in all the complexes
which has been supported by TG/DTA. The thermal behavior of complexes shows that
water molecule is removed in first step-followed removal of anions and then
decomposition of the ligand molecule in subsequent steps. General mechanisms
describing the decomposition of the solid complexes are suggested. Kinetic and
thermodynamic parameters were computed from the thermal decomposition data. The
room temperature magnetic moment values for all the complexes lie in the range of
2.2-2.4BM, indicating departure from spin only values due to second order Zeeman
effect. The electronic spectra indicate planar coordination geometry for all the
complexes. Crystal data for Na[Ni(L)(CH(3)CO(2)(-))]H(2)O: tetragonal, space
group P4/m, a=8.2004A, b=8.2004A, c=16.0226A, V=1077.47A(3), Z=2. Crystal data
for Na[Ni(L)(Cl(-))]H(2)O: cubic, space group Pm3, a=16.1055A, b=16.1055A,
c=16.1055A, V=4178.38A(3), Z=6. Crystal data for Na[Ni(L)(NO(3)(-))]H(2)O:
tetragonal, space group P4/m, a=7.2121A, b=7.2121A, c=12.0200A, V=625.22A(3),
Z=2.
PMID- 17030149
TI - Spectral, electrical conductivity and biological activity properties of some new
azopyrimidine derivatives and their complexes.
AB - The electronic absorption spectra of 5-(o-substituted phenylazo)-6-amino-2
thiouracils and 6-(o-substituted phenylazo)-5-aminouracils containing different
substituents are studied at different pH's. The dissociation constants are
evaluated and discussed. Phenomenon of tautomerism is more supported by (1)H NMR
and (13)C NMR spectra. The electrical conductivity of some ligands and their
Co(II), Ni(II) and Cu(II) complexes in the temperature range 293-150K favoured
their semiconducting properties where the metal ion forms a bridge to facilitate
the flow of the current. The biological activity of some ligands and their
complexes are tested against a number of Gram-positive and Gram-negative
bacteria. The results showed that some of the compounds have a well considerable
activity against some of the organisms.
PMID- 17030150
TI - Transfusion medicine in Norway: new problems and new opportunities.
AB - During 2005 Norwegian Transfusion Medicine has faced some new problems, sought
new solutions and gained strength. Interactions with the public and the health
authorities have been important issues for consideration, which are discussed
below.
PMID- 17030151
TI - Immunological and biochemical responses in Mya arenaria (Mollusca Bivalvia)
exposed in vivo to estradiol-17beta.
AB - Soft-shell clams Mya arenaria were injected with 10, 20 or 40 nmol of estradiol
17beta (E2). We observed a significant inhibiting effect of E2 on phagocytic
activity of hemocytes from clams exposed to 10 and 20 nmol. A dose-response
increase of the glycogen phosphorylase in the gonad tended to show a
remobilisation of glycogen reserves involved in vitellogenesis although the
exposure time must have been too short to observe a decrease in glycogen reserves
or an increase in RNA concentration. Both results corroborate those of other
studies about estrogen involvement in controlling immune capacity and energy
metabolism related to vitellogenesis in bivalves. We can assume that immune
parameters should now be taken into consideration in assessing endocrine
disruption in bivalves. Nevertheless further studies are needed to understand the
controlling pathways of E2 with a special regard on its interactions with other
effectors involved in bivalve immunity and reproduction as well.
PMID- 17030152
TI - The application of genomic and proteomic technologies in predictive, preventive
and personalized medicine.
AB - The long asymptomatic period before the onset of chronic diseases offers good
opportunities for disease prevention. Indeed, many chronic diseases may be
preventable by avoiding those factors that trigger the disease process (primary
prevention) or by use of therapy that modulates the disease process before the
onset of clinical symptoms (secondary prevention). Accurate prediction is vital
for disease prevention so that therapy can be given to those individuals who are
most likely to develop the disease. The utility of predictive markers is
dependent on three parameters, which must be carefully assessed: sensitivity,
specificity and positive predictive value. Specificity is important if a
biomarker is to be used to identify individuals either for counseling or for
preventive therapy. However, a reciprocal relationship exists between sensitivity
and specificity. Thus, successful biomarkers will be highly specific without
sacrificing sensitivity. Unfortunately, biomarkers with ideal specificity and
sensitivity are difficult to find for many diseases. One potential solution is to
use the combinatorial power of a large number of biomarkers, each of which alone
may not offer satisfactory specificity and sensitivity. Recent technological
advances in genetics, genomics, proteomics, and bioinformatics offer a great
opportunity for biomarker discovery. The newly identified biomarkers have the
potential to bring increased accuracy in disease diagnosis and classification, as
well as therapeutic monitoring. In this review, we will use type 1 diabetes (T1D)
as an example, when appropriate, to discuss pertinent issues related to high
throughput biomarker discovery.
PMID- 17030153
TI - Screening for Auditory Impairment-Which Hearing Assessment Test (SAI-WHAT): RCT
design and baseline characteristics.
AB - BACKGROUND: Effective screening programs should not merely detect presence of
disease, but also lead to long-term benefit. We describe the rationale and design
of the first randomized clinical trial to study the long-term effects of routine
screening for hearing loss. We also describe the baseline characteristics of the
randomized cohort. METHODS: We randomized 2305 veterans age 50 years or older to
a control arm without screening, or to screening with: physiologic testing
(AudioScope), a self-administered questionnaire (Hearing Handicap Inventory for
the Elderly-Screening version [HHIE-S]), or both tests. The primary outcome
measure will be hearing aid use one year after screening. We will also study a
number of secondary outcomes, including appointments made with and visits to an
audiologist, cases of aidable hearing loss, hearing aids dispensed, self-rated
communication ability, and hearing-related quality of life. RESULTS: Baseline
demographic and health status measures were evenly distributed across the
screening arms. The percentage of patients who screened positive for hearing loss
was 18.6%, 59.2%, and 63.6% for the AudioScope, HHIE-S, and combined screening
arms, respectively. IMPLICATIONS: Long-term results are needed to gain insight
into whether the AudioScope is associated with high rates of false negative
screening, the HHIE-S is associated with high rates of false positive screening,
or a combination of both. Identifying the best screening program will depend on
determining which strategy leads to successful hearing aid use.
PMID- 17030154
TI - Value of recruitment strategies used in a primary care practice-based trial.
AB - PURPOSE: "Physicians-recruiting-physicians" is the preferred recruitment approach
for practice-based research. However, yields are variable; and the approach can
be costly and lead to biased, unrepresentative samples. We sought to explore the
potential efficiency of alternative methods. METHODS: We conducted a
retrospective analysis of the yield and cost of 10 recruitment strategies used to
recruit primary care practices to a randomized trial to improve cardiovascular
disease risk factor management. We measured response and recruitment yields and
the resources used to estimate the value of each strategy. Providers at recruited
practices were surveyed about motivation for participation. RESULTS: Response to
6 opt-in marketing strategies was 0.40% (53/13290), ranging from 0% to 2.86% by
strategy; 33.96% (18/53) of responders were recruited to the study. Of those
recruited from opt-out strategies, 8.68% joined the study, ranging from 5.35% to
41.67% per strategy. A strategy that combined both opt-in and opt-out approaches
resulted in a 51.14% (90/176) response and a 10.80% (19/90) recruitment rate.
Cost of recruitment was $613 per recruited practice. Recruitment approaches based
on in-person meetings (41.67%), previous relationships (33.33%), and borrowing an
Area Health Education Center's established networks (10.80%), yielded the most
recruited practices per effort and were most cost efficient. Individual providers
who chose to participate were motivated by interest in improving their clinical
practice (80.5%); contributing to CVD primary prevention (54.4%); and
invigorating their practice with new ideas (42.1%). CONCLUSIONS: This analysis
provides suggestions for future recruitment efforts and research. Translational
studies with limited funds could consider multi-modal recruitment approaches
including in-person presentations to practice groups and exploitation of previous
relationships, which require the providers to opt-out, and interactive opt-in
approaches which rely on borrowed networks. These approaches can be supplemented
with non-relationship-based opt-out strategies such as cold calls strategically
targeted to underrepresented provider groups.
PMID- 17030156
TI - Evaluation of the influence of protein precipitation prior to on-line SPE-LC
API/MS procedures using multivariate data analysis.
AB - Matrix effects on mass spectrometry (MS) response were investigated with three
atmospheric pressure ionization (API) sources after on-line solid-phase
extraction (SPE) of human plasma. On-line SPE was evaluated with one restricted
access material (RAM), two large particle supports (LPS) and one monolith. A
sample protein precipitation (PP) with acetonitrile (2:1) and a direct injection
were tested. Principal component analysis (PCA) was performed to simplify data
presentation and interpretation. Protein precipitation was found to be mandatory
for reducing signal modification. Regarding sensitivity towards matrix effects
after PP, atmospheric pressure photoionization (APPI) was globally the least
sensitive ionization mode while electrospray ionization ESI was the most
sensitive.
PMID- 17030155
TI - Rationale and design of the AdRem study: evaluating the effects of blood pressure
lowering and intensive glucose control on vascular retinal disorders in patients
with type 2 diabetes mellitus.
AB - The ADVANCE Retinal Measurements (AdRem) Study is a large intervention study
evaluating the effects of target driven intensive glucose control and placebo
controlled blood pressure lowering on retinal vascular changes. AdRem is a sub
study of the ADVANCE Study (Action in Diabetes and Vascular disease), a 2x2
factorial randomized controlled trial with an ACE inhibitor-diuretic combination
(perindopril-indapamide) and a gliclazide MR-based regimen in patients with type
2 diabetes mellitus. The AdRem study is based on seven-field stereoscopic retinal
photographs of both eyes. These are taken within 3 months after randomization in
ADVANCE (baseline), at the biennial and at the final visit. The primary outcome
is progression of two or more steps in ETDRS classification. Secondary outcomes
include progression of retinal vascular lesions and distortion of retinal
vascular geometry. Retinal photographs are made on film and digitized at a
central laboratory. The AdRem study uses fully digitized quality control and
grading. Between August 2002 and January 2004 1978 patients were included in the
AdRem study, from 39 centers in 14 countries. Approximately 85% comply with the
strict AdRem quality requirements. Publication of the results is expected in
early 2008. The AdRem study is designed to provide reliable evidence on the
effects of intensive glucose control and blood pressure lowering on both diabetic
retinopathy and abnormalities of retinal vasculature in patients with type 2
diabetes mellitus.
PMID- 17030157
TI - Validated GC-MS analysis for the determination of residual fentanyl in applied
Durogesic reservoir and Durogesic D-Trans matrix transdermal fentanyl patches.
AB - The method development and validation characteristics are described of a simple
gas chromatographic-mass spectrometric (GC-MS) analytical procedure to determine
residual fentanyl in used Durogesic reservoir patches and Durogesic D-Trans
matrix technology based systems to estimate the actual rate of transdermal
fentanyl delivered in individual patients. The sample preparation protocol
constituting a saline based extraction of sets of new patches of each nominal
dose available, resulted in fentanyl extraction recoveries to increase steadily
as a function of increasing extraction time. For the reservoir type transdermal
therapeutic system (TTS), fentanyl extraction efficiencies at equilibrium (16 h)
ranged from approximately 60% (100-microg/h TTS) to 95% (25-microg/h TTS),
whereas for the matrix type system considerable lower recoveries were
demonstrated for the highest nominal dose rates (35%-52%), while reaching 90% for
the 25-microg/h system. For the latter type of fentanyl TTS, an optimized
methanol based extraction protocol yielded virtually quantitative fentanyl
recoveries for each matrix patch nominal dose level at substantially shorter
extraction periods (15 min). The GC-MS analytical method using selected ion
monitoring (SIM) and deuterated fentanyl as internal standard was shown to be
adequately selective with regard to the presence of other compounds in the
Durogesic patches. It was further demonstrated that the developed analytical
protocols provided highly reproducible and accurate estimates of the initial
fentanyl content of each patch type at all available nominal doses, with
coefficients of variation and relative errors generally below 10%. These
advantageous assay validation characteristics can be further transposed to the
application of residual fentanyl level estimates in used patches, provided that
with each batch of samples also a set of new TTSs with equal dose is assayed to
perfectly mimic extraction phenomena. Finally, the presented GC-MS analytical
protocol was successfully applied for the determination of residual fentanyl in a
subset of 57 reservoir type patches obtained from four palliative patients.
PMID- 17030158
TI - Protein A chromatography for antibody purification.
AB - Staphylococcal protein A (SPA) is one of the first discovered immunoglobulin
binding molecules and has been extensively studied during the past decades. Due
to its affinity to immunoglobulins, SPA has found widespread use as a tool in the
detection and purification of antibodies and the molecule has been further
developed to one of the most employed affinity purification systems.
Interestingly, a minimized SPA derivative has been constructed and a domain
originating from SPA has been improved to withstand the harsh environment
employed in industrial purifications. This review will focus on the development
of different affinity molecules and matrices for usage in antibody purification.
PMID- 17030165
TI - Obesity epidemic in need of answers.
PMID- 17030159
TI - How tough is bone? Application of elastic-plastic fracture mechanics to bone.
AB - Bone, with a hierarchical structure that spans from the nano-scale to the macro
scale and a composite design composed of nano-sized mineral crystals embedded in
an organic matrix, has been shown to have several toughening mechanisms that
increases its toughness. These mechanisms can stop, slow, or deflect crack
propagation and cause bone to have a moderate amount of apparent plastic
deformation before fracture. In addition, bone contains a high volumetric
percentage of organics and water that makes it behave nonlinearly before
fracture. Many researchers used strength or critical stress intensity factor
(fracture toughness) to characterize the mechanical property of bone. However,
these parameters do not account for the energy spent in plastic deformation
before bone fracture. To accurately describe the mechanical characteristics of
bone, we applied elastic-plastic fracture mechanics to study bone's fracture
toughness. The J integral, a parameter that estimates both the energies consumed
in the elastic and plastic deformations, was used to quantify the total energy
spent before bone fracture. Twenty cortical bone specimens were cut from the mid
diaphysis of bovine femurs. Ten of them were prepared to undergo transverse
fracture and the other 10 were prepared to undergo longitudinal fracture. The
specimens were prepared following the apparatus suggested in ASTM E1820 and
tested in distilled water at 37 degrees C. The average J integral of the
transverse-fractured specimens was found to be 6.6 kPa m, which is 187% greater
than that of longitudinal-fractured specimens (2.3 kPa m). The energy spent in
the plastic deformation of the longitudinal-fractured and transverse-fractured
bovine specimens was found to be 3.6-4.1 times the energy spent in the elastic
deformation. This study shows that the toughness of bone estimated using the J
integral is much greater than the toughness measured using the critical stress
intensity factor. We suggest that the J integral method is a better technique in
estimating the toughness of bone.
PMID- 17030166
TI - Diagnostic colonoscopy: the end is coming.
PMID- 17030167
TI - Clinical challenges and images in GI. Portal cavernoma-associated cholangiopathy.
PMID- 17030168
TI - Clinical challenges and images in GI. Pill esophagitis.
PMID- 17030169
TI - Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase
Ib, placebo-controlled, randomized study.
AB - BACKGROUND & AIMS: VX-950 specifically inhibits the NS3.4A protease of hepatitis
C and has antiviral activity in vitro. This phase I, placebo-controlled, double
blind study evaluated the antiviral activity, pharmacokinetics, and safety of VX
950 in patients with chronic hepatitis C (CHC). METHODS: Thirty-four patients
with genotype 1 CHC were randomized to receive placebo or VX-950 at doses of 450
mg or 750 mg every 8 hours or 1250 mg every 12 hours for 14 days. Of the 34
participants, 27 (79%) had failed prior treatment. Patients were monitored for
safety and tolerability of VX-950. Plasma VX-950 concentrations and HCV RNA
levels were measured. RESULTS: VX-950 was well tolerated and had substantial
antiviral effects: viral loads dropped > or =2 log(10) in all 28 patients treated
with VX-950 and > or =3 log(10) in 26 (93%) of the 28 patients. In the 750-mg
dose group, which had the highest trough plasma drug concentrations, the median
reduction of HCV RNA was 4.4 log(10) after 14 days. In the 450-mg and 1250-mg
groups, the maximal effect was seen between days 3 and 7 of dosing, and median
HCV RNA increased between days 7 and 14; median reductions at day 14 were 2.4
log(10) and 2.2 log(10), respectively. Median alanine aminotransferase levels
decreased during dosing in all VX-950 groups. CONCLUSIONS: VX-950 was well
tolerated and demonstrated substantial antiviral activity. Some patients had
viral breakthrough during dosing, related to selection of variants with decreased
sensitivity to VX-950. The results support further studies of VX-950 in patients
with CHC.
PMID- 17030170
TI - Relationship of abdominal bloating to distention in irritable bowel syndrome and
effect of bowel habit.
AB - BACKGROUND & AIMS: The relationship between the sensation of bloating, often
ranked as the most bothersome symptom by patients with irritable bowel syndrome
(IBS), and actual distention manifest as an increase in abdominal girth is
controversial. Investigation of this problem has been hampered by the lack of a
reliable ambulatory technique to measure abdominal girth. The aim of this study
was to use the technique of abdominal inductance plethysmography to compare
diurnal variation in girth in IBS patients and healthy volunteers, relating these
changes to the sensation of bloating. METHODS: Abdominal girth was recorded for
24 hours in 20 IBS-constipation (age, 18-73 y), 20 IBS-diarrhea (age, 25-62 y)
and 10 IBS-alternating (age, 21-59 y) female patients meeting Rome II criteria
and 20 healthy female controls (age, 18-67 y). All subjects pursued normal daily
activities, recording their symptoms of bloating and pain together with bowel
habit. RESULTS: All patients with IBS, irrespective of bowel habit, reported
significantly greater bloating than controls (P < .0001). Forty-eight percent of
patients also showed distention beyond the 90% control range, with this being
most prominent in IBS-constipation. Bloating correlated strongly only with
distention in IBS-constipation (r > or = 0.48; P < or = .02). Neither bloating
nor distention in IBS was related to body mass index, age, parity, or psychologic
status. CONCLUSIONS: Abdominal distention is a clearly definable phenomenon in
IBS that can reach 12 cm. However, it only occurs in half of patients reporting
bloating, and the 2 only correlate in IBS-constipation. Bloating and distention
may differ pathophysiologically and this appears to be reflected in the bowel
habit subtype.
PMID- 17030171
TI - Risk stratification for colon neoplasia: screening strategies using colonoscopy
and computerized tomographic colonography.
AB - BACKGROUND & AIMS: We developed a risk index to identify low-risk patients who
may be screened for colorectal cancer with computerized tomographic colonography
(CTC) instead of colonoscopy. METHODS: Asymptomatic persons aged 50 years or
older who had undergone screening colonoscopy were randomized retrospectively to
derivation (n = 1512) and validation (n = 1493) subgroups. We developed a risk
index (based on age, sex, and family history) from the derivation group. The
expected results of 3 screening strategies--universal colonoscopy, universal CTC,
and a stratified strategy of colonoscopy for high-risk and CTC for low-risk
patients--were then compared. Outcomes for the 3 strategies were extrapolated
from the known colonic findings in each patient, using sensitivity/specificity
values for CTC from the medical literature. Results were validated in the
validation subgroup. RESULTS: In the derivation subgroup, universal colonoscopy
detected 94% of advanced neoplasia and universal CTC detected only 70% and
resulted in the largest total number of procedures and number of patients
undergoing both procedures. The stratified strategy detected 92% of advanced
neoplasia, requiring colonoscopy in 68% and CTC in 36% of patients, with only 4%
having to undergo both procedures. In the validation subgroup, universal
colonoscopy detected 94% and universal CTC detected 71% of advanced neoplasia,
whereas the stratified strategy detected 89%, requiring colonoscopy in 64% and
CTC in 40%. Unlike universal CTC, the stratified strategy was independent of
assumptions for CTC sensitivity, specificity, and threshold for colonoscopy.
CONCLUSIONS: The stratified strategy based on our risk index may optimize the
yield of colonoscopic resources and reduce the number of patients undergoing
colonoscopy.
PMID- 17030172
TI - Increased serum levels of complement C3a anaphylatoxin indicate the presence of
colorectal tumors.
AB - BACKGROUND & AIMS: Late diagnosis of colorectal carcinoma results in a
significant reduction of average survival times. Yet despite screening programs,
about 70% of tumors are detected at advanced stages (International Union Against
Cancer stages III/IV). We explored whether detection of malignant disease would
be possible through identification of tumor-specific protein biomarkers in serum
samples. METHODS: A discovery set of sera from patients with colorectal
malignancy (n = 58) and healthy control individuals (n = 32) were screened for
potential differences using surface-enhanced laser desorption/ionization time-of
flight mass spectrometry. Candidate proteins were identified and their expression
levels were validated in independent sample sets using a specific immunoassay
(enzyme-linked immunosorbent assay). RESULTS: By using class comparison and
custom-developed algorithms we identified several m/z values that were expressed
differentially between the malignant samples and the healthy controls of the
discovery set. Characterization of the most prominent m/z values revealed a
member of the complement system, the stable form of C3a anaphylatoxin (ie, C3a
desArg). Based on a specific enzyme-linked immunosorbent assay, serum levels of
complement C3a-desArg predicted the presence of colorectal malignancy in a
blinded validation set (n = 59) with a sensitivity of 96.8% and a specificity of
96.2%. Increased serum levels were also detected in 86.1% of independently
collected sera from patients with colorectal adenomas (n = 36), whereas only 5.6%
were classified as normal. CONCLUSIONS: Complement C3a-desArg is present at
significantly higher levels in serum from patients with colorectal adenomas (P <
.0001) and carcinomas (P < .0001) than in healthy individuals. This suggests that
quantification of C3a-desArg levels could ameliorate existing screening tests for
colorectal cancer.
PMID- 17030173
TI - Relative contribution of genetic and nongenetic modifiers to intestinal
obstruction in cystic fibrosis.
AB - BACKGROUND & AIMS: Neonatal intestinal obstruction (meconium ileus [MI]) occurs
in 15% of patients with cystic fibrosis (CF). Our aim was to determine the
relative contribution of genetic and nongenetic modifiers to the development of
this major complication of CF. METHODS: A total of 65 monozygous twin pairs, 23
dizygous twin/triplet sets, and 349 sets of siblings with CF were analyzed for MI
status, significant covariates, and genome-wide linkage. RESULTS: Specific
mutations in the CF transmembrane conductance regulator (CFTR), the gene
responsible for CF, correlated with MI, indicating a role for CFTR genotype.
Monozygous twins showed substantially greater concordance for MI than dizygous
twins and siblings (P = 1 x 10(-5)), showing that modifier genes independent of
CFTR contribute substantially to this trait. Regression analysis revealed that MI
was correlated with distal intestinal obstruction syndrome (P = 8 x 10(-4)).
Unlike MI, concordance analysis indicated that the risk for development of distal
intestinal obstruction syndrome in CF patients is caused primarily by nongenetic
factors. Regions of suggestive linkage (logarithm of the odds of linkage >2.0)
for modifier genes that cause MI (chromosomes 4q35.1, 8p23.1, and 11q25) or
protect from MI (chromosomes 20p11.22 and 21q22.3) were identified by genome-wide
analyses. These analyses did not support the existence of a major modifier gene
on chromosome 19 in a region previously linked to MI. CONCLUSIONS: The CFTR gene
along with 2 or more modifier genes are the major determinants of intestinal
obstruction in newborn CF patients, whereas intestinal obstruction in older CF
patients is caused primarily by nongenetic factors.
PMID- 17030174
TI - Effect of ribavirin in genotype 1 patients with hepatitis C responding to
pegylated interferon alfa-2a plus ribavirin.
AB - BACKGROUND & AIMS: Pegylated interferon alfa-ribavirin combination is the
standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin
enhances the rate of sustained hepatitis C virus (HCV) eradication remain
unknown. We aimed to investigate the role of ribavirin in HCV clearance during
therapy and to evaluate the consequences of ribavirin discontinuation in patients
infected with genotype 1 hepatitis C who cleared HCV RNA at week 24. METHODS: A
total of 516 patients were treated with pegylated interferon alfa-2a, 180
microg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week
24. They were randomized to continue with the combination or receive pegylated
interferon alone. RESULTS: Responders at week 24 who stopped ribavirin had a
significantly higher rate of breakthroughs during, and relapses after, therapy
(sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect
profile and quality of life tended to improve. Multiple logistic regression
analysis in the pegylated interferon alfa monotherapy group allowed
identification of responders at week 24 who could stop ribavirin without losing
their chance of a sustained virologic response, based on baseline viral load and
age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is
undetectable at week 2. CONCLUSIONS: We made 3 conclusions from this study.
First, ribavirin primarily acts by sustaining the virologic response to pegylated
interferon alfa; second, ribavirin must be administered for the full treatment
duration in most genotype 1-infected patients who respond; third, baseline
parameters may help identify patients who could discontinue ribavirin or reduce
the dose without losing their chance of success.
PMID- 17030175
TI - Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with
advanced cirrhosis and hemorrhage.
AB - BACKGROUND & AIMS: Oral norfloxacin is the standard of therapy in the prophylaxis
of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage.
However, during the last years, the epidemiology of bacterial infections in
cirrhosis has changed, with a higher incidence of infections caused by quinolone
resistant bacteria. This randomized controlled trial was aimed to compare oral
norfloxacin vs intravenous ceftriaxone in the prophylaxis of bacterial infection
in cirrhotic patients with gastrointestinal bleeding. METHODS: One hundred eleven
patients with advanced cirrhosis (at least 2 of the following: ascites, severe
malnutrition, encephalopathy, or bilirubin >3 mg/dL) and gastrointestinal
hemorrhage were randomly treated with oral norfloxacin (400 mg twice daily; n =
57) or intravenous ceftriaxone (1 g/day; n = 54) for 7 days. The end point of the
trial was the prevention of bacterial infections within 10 days after inclusion.
RESULTS: Clinical data were comparable between groups. The probability of
developing proved or possible infections, proved infections, and spontaneous
bacteremia or spontaneous bacterial peritonitis was significantly higher in
patients receiving norfloxacin (33% vs 11%, P = .003; 26% vs 11%, P = .03; and
12% vs 2%, P = .03, respectively). The type of antibiotic used (norfloxacin),
transfusion requirements at inclusion, and failure to control bleeding were
independent predictors of infection. Seven gram-negative bacilli were isolated in
the norfloxacin group, and 6 were quinolone resistant. Non-enterococcal
streptococci were only isolated in the norfloxacin group. No difference in
hospital mortality was observed between groups. CONCLUSIONS: Intravenous
ceftriaxone is more effective than oral norfloxacin in the prophylaxis of
bacterial infections in patients with advanced cirrhosis and hemorrhage.
PMID- 17030176
TI - Utility of a new model to diagnose an alcohol basis for steatohepatitis.
AB - BACKGROUND & AIMS: Distinguishing an alcohol basis from a nonalcoholic basis for
the clinical and histologic spectrum of steatohepatitic liver disease is
difficult because of unreliability of alcohol consumption history. Unfortunately,
various biomarkers have had limited utility in distinguishing alcoholic liver
disease (ALD) from nonalcoholic fatty liver disease (NAFLD). Thus, the aim of our
study was to create and validate a model to diagnose ALD in patients with
steatohepatitis. METHODS: A cross-sectional cohort study was performed at the
Mayo Clinic, Rochester, Minnesota, to create a model using multivariable logistic
regression analysis. This model was validated in 3 independent data sets
comprising patients of varying severity of steatohepatitis spanning over 10
years. RESULTS: Logistic regression identified mean corpuscular volume, aspartate
aminotransferase (AST)/alanine aminotransferase (ALT) ratio, body mass index, and
gender as the most important variables that separated patients with ALD from
NAFLD. These variables were used to generate the ALD/NAFLD Index (ANI), with ANI
of greater than zero incrementally favoring ALD and ANI of less than zero
incrementally favoring a diagnosis of NAFLD, thus making ALD unlikely. ANI had a
c-statistic of 0.989 in the derivation sample, and 0.974, 0.989, 0.767 in the 3
validation samples. ANI performance characteristics were significantly better
than several conventional and recently proposed biomarkers used to differentiate
ALD from NAFLD, including the histopathologic marker protein tyrosine phosphatase
1b, AST/ALT ratio, gamma-glutamyl transferase, and carbohydrate-deficient
transferrin. CONCLUSIONS: ANI, derived from easily available objective variables,
accurately differentiates ALD from NAFLD in hospitalized, ambulatory, and
pretransplantation patients and compares favorably with other traditional and
proposed biomarkers.
PMID- 17030177
TI - Advanced cytologic techniques for the detection of malignant pancreatobiliary
strictures.
AB - BACKGROUND & AIMS: Two advanced cytologic techniques for detecting aneuploidy
digital image analysis (DIA) and fluorescence in situ hybridization (FISH)-have
recently been developed to help identify malignant pancreatobiliary strictures.
The aim of this study was to assess the clinical utility of cytology, DIA, and
FISH for the identification of malignant pancreatobiliary strictures. METHODS:
Brush cytologic specimens from 233 consecutive patients undergoing endoscopic
retrograde cholangiopancreatography for pancreatobiliary strictures were examined
by all 3 (cytology, DIA, and FISH) techniques. Strictures were stratified as
proximal (n = 33) or distal (n = 114) based on whether they occurred above or
below the cystic duct, respectively. Strictures in patients with primary
sclerosing cholangitis (n = 86) were analyzed separately. RESULTS: Despite the
stratification, the performances of the tests were similar. Conventional cytology
has a low sensitivity (4%-20%) but 100% specificity. Because of the high
specificity for cytology, we assessed the performance of the other tests when
conventional cytology was negative. In this clinical context, FISH had an
increased sensitivity (35%-60%) when assessing for chromosomal gains (polysomy)
while preserving the specificity of cytology. The sensitivity and specificity of
DIA was intermediate as compared with routine cytology and FISH but was additive
to FISH values demonstrating only trisomy of chromosome 7 or chromosome 3.
CONCLUSIONS: These findings suggest that FISH and DIA increase the sensitivity
for the diagnosis of malignant pancreatobiliary tract strictures over that
obtained by conventional cytology while maintaining an acceptable specificity.
PMID- 17030178
TI - STAT3 activation regulates growth, inflammation, and vascularization in a mouse
model of gastric tumorigenesis.
AB - BACKGROUND & AIMS: The gp130(757F/F) mouse is a well-characterized and robust
model of distal gastric tumorigenesis displaying many of the characteristics of
human intestinal type gastric cancer. Key to the development of tumors in this
model, and in many examples of human tumor development, is hyperactivation of the
transcription factor STAT3. This study addressed the requirement for STAT3
activation in tumor initiation and characterized some of the genes downstream of
STAT3 required for tumor development. Furthermore, the interaction among STAT3,
the microbial environment, and tumorigenesis was evaluated. METHODS: The role of
STAT3 in gastric tumor development was assessed in detail in
gp130(757F/Y757F):STAT3(+/-) mice displaying reduced STAT3 activity. Tumor size
was quantified morphologically, and the effects on endocrine cell populations,
neovascularization, and inflammatory cell infiltration as well as the outcome of
STAT3 activation on transcription of a number of genes relevant in growth and
inflammation were quantified. RESULTS: Loss of one STAT3 allele in gp130(757F/F)
mice reduced the frequency and rate of tumor development because of inhibition of
proliferation-induced glandular hyperplasia. There was also a concomitant
reduction in the degree of inflammatory infiltration and cytokine and chemokine
expression, angiogenesis, and expression of metalloproteinases and growth
factors. Antimicrobial treatment of gp130(757F/F) mice slowed tumor growth
coincident with reduced macrophage and neutrophil infiltration. CONCLUSIONS:
Activation of STAT3 and the microbial environment are pivotal for gastric tumor
initiation and development in the gp130(757F/F) mouse, thus supporting the notion
that STAT3 activation may play a role in human gastric cancer development.
PMID- 17030179
TI - Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling
and prostaglandin E2 pathway.
AB - BACKGROUND & AIMS: Accumulating evidence indicates that prostaglandin E(2)
(PGE(2)), a downstream product of cyclooxygenase 2 (COX-2), plays a key role in
gastric tumorigenesis. The Wnt pathway is also suggested to play a causal role in
gastric carcinogenesis. However, the molecular mechanism remains poorly
understood of how the Wnt and PGE(2) pathways contribute to gastric
tumorigenesis. To investigate the role of Wnt and PGE(2) in gastric cancer, we
have generated transgenic mice that activate both pathways and examined their
phenotypes. METHODS: We constructed K19-Wnt1 transgenic mice expressing Wnt1 in
the gastric mucosa using the keratin 19 promoter. We then crossed K19-Wnt1 mice
with another transgenic line, K19-C2mE, to obtain K19-Wnt1/C2mE compound
transgenic mice. The K19-C2mE mice express COX-2 and microsomal prostaglandin E
synthase-1 (mPGES-1) in the stomach, showing an increased gastric PGE(2) level.
We examined the gastric phenotypes of both K19-Wnt1 and K19-Wnt1/C2mE mice.
RESULTS: K19-Wnt1 mice had a significant suppression of epithelial
differentiation and developed small preneoplastic lesions consisting of
undifferentiated epithelial cells with macrophage accumulation. Importantly,
additional expression of COX-2 and mPGES-1 converted the preneoplastic lesions in
the K19-Wnt1 mice into dysplastic gastric tumors by 20 weeks of age. Notably, we
found mucous cell metaplasia in the glandular stomach of the K19-Wnt1/C2mE mice
as early as 5 weeks of age, before the dysplastic tumor development. CONCLUSIONS:
Wnt signaling keeps the gastric progenitor cells undifferentiated. Simultaneous
activation of both Wnt and PGE(2) pathways causes dysplastic gastric tumors
through the metaplasia-carcinoma sequence.
PMID- 17030180
TI - APC and oncogenic KRAS are synergistic in enhancing Wnt signaling in intestinal
tumor formation and progression.
AB - BACKGROUND & AIMS: Synchronous activation of the Wnt signaling pathway, mostly
because of loss of function of the APC tumor suppressor, and of the oncogenic
KRAS-signaling pathway is very frequent in colorectal cancer and is associated
with poor prognosis. METHODS: We have generated a compound transgenic mouse
model, KRAS(V12G)/Apc(+/1638N), to recapitulate the human disease and compared it
with single transgenic littermates. RESULTS: Compound mutant mice are
characterized by a 10-fold increase in tumor multiplicity and by accelerated
tumor progression, resulting in strongly enhanced morbidity and mortality. Tumors
from compound mutant mice proliferate faster and show decreased levels of
apoptosis. Several lines of evidence indicate that the observed increase in tumor
multiplicity and malignant transformation is caused by the synergistic activation
of Wnt signaling in cells with oncogenic KRAS and loss-of-function Apc mutations.
Activated KRAS is known to induce tyrosine phosphorylation of beta-catenin,
leading to its release from E-cadherin at the adherens junction. This results in
an increased beta-catenin pool in the cytoplasma, its subsequent translocation to
the nucleus, and the transcriptional activation of Wnt downstream target genes.
Accordingly, intestinal tumors from KRAS(V12G)/Apc(+/1638N) mice show a
significant increase in cells with nuclear accumulation of beta-catenin when
compared with Apc(+/1638N) animals. Moreover, Apc/KRAS-mutant embryonic stem
cells show a significantly enhanced beta-catenin/T-cell factor-mediated
transcriptional activation, accompanied by increased beta-catenin nuclear
localization. CONCLUSIONS: This KRAS-induced increase in Wnt/beta-catenin
signaling may enhance the plasticity and self-renewal capacity of the tumor, thus
resulting in the drastically augmented tumor multiplicity and malignant behavior
in compound mutant animals.
PMID- 17030181
TI - Human thioredoxin-1 ameliorates experimental murine colitis in association with
suppressed macrophage inhibitory factor production.
AB - BACKGROUND & AIMS: Thioredoxin-1 (TRX) is a small multifunctional protein with
antioxidative and redox-regulating functions. In this study, we investigated the
significance of TRX in patients with inflammatory bowel disease (IBD) and the
ability and mechanism to ameliorate experimental colitis. METHODS: Serum TRX and
macrophage migration inhibitory factor (MIF) levels were measured in patients
with IBD. The effects of TRX were evaluated in a dextran sulfate sodium (DSS)
induced colitis model by comparing TRX-overexpressing transgenic (TRX-TG) and
control mice. We further evaluated the effect of recombinant human TRX (rhTRX)
administration on DSS-induced colitis and colonic inflammation of interleukin
(IL)-10 knockout (IL-10 KO) mice. Colonic inflammation was examined clinically
and histologically. Proinflammatory cytokine levels were examined in colonic
tissues, and MIF levels were measured in colonic tissues and sera in mice. The
effect of TRX on MIF production was also analyzed in vitro. RESULTS: Serum TRX
and MIF levels were significantly higher in patients with IBD than normal
controls, and TRX levels correlated with disease activity. TRX significantly
ameliorated DSS-induced colitis and colonic inflammation of IL-10 KO mice.
Increase of tumor necrosis factor-alpha and interferon-gamma in colonic tissues
was significantly suppressed in TRX-TG mice compared with wild-type mice. MIF
levels in colonic tissues and sera were significantly lower in TRX-TG mice than
in wild-type mice, irrespective of DSS administration. Anti-TRX treatment
exacerbated DSS-induced colitis. In vitro studies demonstrated that rhTRX
suppressed MIF production in human monocyte cells. CONCLUSIONS: TRX might have a
potential as a novel therapeutic agent for the treatment of IBD.
PMID- 17030182
TI - The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel
disease in a murine model.
AB - BACKGROUND & AIMS: The recently proposed Inflammatory Reflex describes an
interaction between the vagus nerve and peripheral macrophages, resulting in
attenuation of proinflammatory cytokine release in response to systemic exposure
to bacterial endotoxin. The purpose of this study was to determine whether a
similar vagus/macrophage axis modulates the inflammatory responses in the colon
in mice. METHODS: We assessed the Disease Activity Index (DAI), macroscopic and
histologic damage, serum amyloid-P level, and myeloperoxidase activity in colitis
induced by administration of dextran sodium sulfate (DSS) in healthy and
vagotomized C57BL/6 and in mice deficient in macrophage-colony stimulating factor
(M-CSF)-induced and in hapten-induced colitis. A pyloroplasty was performed in
vagotomized mice. RESULTS: DAI, macroscopic and histologic scores,
myeloperoxidase activity, levels of serum amyloid-P, and colonic tissue levels of
interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were increased
significantly in vagotomized mice 5 days post-DSS and 3 days after hapten-induced
colitis compared with sham-operated mice that received DSS or the hapten.
Pretreatment with nicotine significantly decreased each of these markers in
vagotomized mice with DSS colitis, and all markers except DAI and IL-6 in sham
operated DSS-treated mice. Conversely, hexamethonium treatment significantly
increased each of these markers in the sham-operated DSS-treated mice. Vagotomy
had no effect on the colitis in M-CSF-deficient mice. CONCLUSIONS: The vagus
nerve plays a counterinflammatory role in acute colitis via a macrophage
dependent mechanism, involving hexamethonium-sensitive nicotinic receptors. The
identification of a counterinflammatory neural pathway would open new therapeutic
avenues for treating acute exacerbations of inflammatory bowel disease.
PMID- 17030183
TI - Altered gastrointestinal and metabolic function in the GPR39-obestatin receptor
knockout mouse.
AB - BACKGROUND & AIMS: The G-protein-coupled receptor GPR39 is a member of a family
that includes the receptors for ghrelin and motilin. Recently the peptide
obestatin was identified as a natural ligand for GPR39. The objective of this
study was to gain insight into the biological function of the GPR39 receptor.
METHODS: GPR39(-/-) mice were generated and analyzed. RESULTS: Endogenous GPR39
expression was detected in the brain (septum-amygdala) and the gastrointestinal
system (parietal cells, enterocytes, neurons, and pancreas). Gastric emptying of
a solid meal (measured by the (14)C octanoic breath test) in GPR39(-/-) mice was
accelerated significantly with a gastric half-emptying time of 49.5 +/- 2.2
minutes compared with 86.9 +/- 8.4 minutes in GPR39(+/+) mice. A more effective
expulsion of distally located pellets (30%-75% of length) was observed in the
colon of GPR39(-/-) mice. Four hours after pylorus ligation, the volume of
gastric secretion was increased significantly (GPR39(-/-): 638 +/- 336 microL;
GPR39(+/+): 225 +/- 170 microL), but gastric acid secretion was unchanged. The
mature body weight and body fat composition of GPR39(-/-) mice was significantly
higher compared with GPR39(+/+) mice, but this was not related to hyperphagia
because 24-hour food intake did not differ between both genotypes. In contrast,
deficiency of the GPR39 receptor led to reduced hyperphagia after fasting. The
cholesterol levels were increased significantly in the GPR39(-/-) mice.
CONCLUSIONS: Our data partially confirm and extend the described in vivo effects
of obestatin and suggest that this peptide plays a functional role in the
regulation of gastrointestinal and metabolic function through interaction with
the GPR39 receptor.
PMID- 17030184
TI - Nitric oxide-induced down-regulation of beta-catenin in colon cancer cells by a
proteasome-independent specific pathway.
AB - BACKGROUND & AIMS: We have previously reported that nitric oxide could induce the
death of colon cancer cells. Because an inappropriate activation of beta-catenin
has been associated with intestinal cell malignant transformation, we explored
whether nitric oxide could affect beta-catenin expression and function. METHODS:
Human colon cancer cell lines were treated with the nitric oxide donor glyceryl
trinitrate (GTN) before analyzing beta-catenin expression by immunofluorescence,
immunoblotting, and immunoprecipitation methods and its transcriptional activity
using a luciferase reporter gene driven by a T-cell factor-responsive promotor.
RESULTS: GTN induces beta-catenin degradation and down-regulates its
transcriptional activity in colon cancer cells. This effect is preceded by GTN
induced tyrosine nitration of beta-catenin, together with its dephosphorylation
on serine 33, 37, and 45 and threonine 41. GTN-induced beta-catenin degradation
involves proteases that are sensitive to a broad-spectrum caspase inhibitor, z
VAD-fmk, and to serine protease inhibitors N-tosyl-L-phenylalaline chloromethyl
ketone (TPCK) and [4-(2-aminoethyl)-benzenesulfonylfluoride] (AEBSF), whereas the
ubiquitin/proteasome pathway is not involved. Interestingly, only TPCK and AEBSF
restore beta-catenin transcriptional activity and preserve beta-catenin nuclear
localization in GTN-treated colon cancer cells. CONCLUSIONS: Exposure of colon
cancer cells to nitric oxide unraveled a so-far-unidentified mechanism of beta
catenin regulation. The protein is nitrated and dephosphorylated, and its
transcriptional activity is reduced through degradation by a TPCK and AEBSF
sensitive protease.
PMID- 17030186
TI - Glial-derived neurotrophic factor modulates enteric neuronal survival and
proliferation through neuropeptide Y.
AB - BACKGROUND & AIMS: Glial-derived neurotrophic factor (GDNF) promotes the survival
and proliferation of enteric neurons. Neuropeptide Y (NPY) is an important
peptide regulating gastrointestinal motility. The role of NPY on the survival and
proliferation of enteric neurons is not known. We examined the effects of GDNF on
the expression and release of NPY from enteric neurons and the role of NPY in
promoting enteric neuronal proliferation and survival. METHODS: Studies were
performed in primary enteric neuronal cultures and NPY knockout mice (NPY(-/-)).
GDNF-induced expression of NPY was assessed by reverse-transcription polymerase
chain reaction (RT-PCR), immunocytochemistry, and enzyme-linked immunosorbent
assay. Using NPY-siRNA and NPY-Y1 receptor antagonist, we examined the role of
NPY in mediating the survival and proliferation effects of GDNF. Gastrointestinal
motility was assessed by measuring gastric emptying, intestinal transit, and
isometric muscle recording from intestinal muscle strips. RESULTS: GDNF induced a
significant increase in NPY messenger RNA and protein expression in primary
enteric neurons and the release of NPY into the culture medium. NPY (1 mumol/L)
significantly increased proliferation of neurons and reduced apoptosis. In the
presence of NPY-siRNA and NPY-Y1 receptor antagonist or in enteric neurons
cultured from NPY(-/-) mice, GDNF-mediated neuronal proliferation and survival
was reduced. NPY increased the phosphorylation of Akt, a downstream target of the
PI-3-kinase pathway. In NPY(-/-) mice, there were significantly fewer nNOS
containing enteric neurons compared with wild-type (WT) mice. NPY(-/-) mice had
accelerated gastric emptying and delayed intestinal transit compared with WT
mice. CONCLUSIONS: We demonstrate that NPY acts as an autocrine neurotrophic
factor for enteric neurons.
PMID- 17030185
TI - IFN-gamma-induced TNFR2 expression is required for TNF-dependent intestinal
epithelial barrier dysfunction.
AB - BACKGROUND & AIMS: Tumor necrosis factor (TNF) plays a critical role in
intestinal disease. In intestinal epithelia, TNF causes tight junction disruption
and epithelial barrier loss by up-regulating myosin light chain kinase (MLCK)
activity and expression. The aim of this study was to determine the signaling
pathways by which TNF causes intestinal epithelial barrier loss. METHODS: Caco-2
cells that were either nontransfected or stably transfected with human TNF
receptor 1 (TNFR1) or TNFR2 and mouse colonocytes were used for physiologic,
morphologic, and biochemical analyses. RESULTS: Colitis induced in vivo by
adoptive transfer of CD4(+)CD45RB(hi) T cells was associated with increased
epithelial MLCK expression and myosin II regulatory light chain (MLC)
phosphorylation as well as morphologic tight junction disruption. In vitro
studies showed that TNF caused similar increases in MLCK expression and MLC
phosphorylation, as well as barrier dysfunction, in Caco-2 monolayers only after
interferon (IFN)-gamma pretreatment. This reductionist model was therefore used
to determine the molecular mechanism by which IFN-gamma and TNF synergize to
cause intestinal epithelial barrier loss. IFN-gamma priming increased TNFR1 and
TNFR2 expression, and blocking antibody studies showed that TNFR2, but not TNFR1,
was required for TNF-induced barrier dysfunction. Transgenic TNFR2, but not
TNFR1, expression allowed IFN-gamma-independent TNF responses. CONCLUSIONS: IFN
gamma primes intestinal epithelia to respond to TNF by inducing TNFR2 expression,
which in turn mediates TNF-induced MLCK-dependent barrier dysfunction. The data
further suggest that epithelial TNFR2 blockade may be a novel approach to restore
barrier function in intestinal disease.
PMID- 17030187
TI - The motogenic effects of cyclic mechanical strain on intestinal epithelial
monolayer wound closure are matrix dependent.
AB - BACKGROUND & AIMS: Complex deformation during normal digestion due to peristalsis
or villous motility may be trophic for the intestinal mucosa. Because tissue
fibronectin is increased in inflammatory states that may accompany mucosal
injury, we evaluated the effects of cyclic mechanical strain and fibronectin on
intestinal epithelial monolayer wound closure in Caco-2 and IEC-6 intestinal
epithelial cells. METHODS: Wounds created in intestinal epithelial monolayers
were subjected to cyclic deformation. Wound closure was assessed by morphometry
using microscopic imaging. Cell signals were assessed by Western blot and
confocal microscopy. RESULTS: Mechanical strain stimulated wound closure on
fibronectin but inhibited closure on collagen in Caco-2 and IEC-6 cells. The
effect was independent of proliferation or cell spreading. Myosin light chain
(MLC) and extracellular signal-regulated kinase (ERK) were phosphorylated in
response to strain in confluent monolayers on both collagen and fibronectin.
Blocking MLC or ERK phosphorylation inhibited the motogenic effect of strain on
fibronectin. Although phosphorylated MLC was redistributed to the leading edge of
migrating cells following 6 hours of strain on collagen and fibronectin,
phosphorylated ERK was redistributed to the lamellipodial edge only on
fibronectin. CONCLUSIONS: Strain promotes intestinal epithelial wound closure by
a pathway requiring ERK and MLC kinase. Fibronectin-dependent ERK redistribution
in response to strain in confluent migrating cells may explain the matrix
dependence of the motogenic effect. Repetitive deformation stimulates intestinal
epithelial proliferation on a collagen substrate, but not fibronectin.
Deformation may exert matrix-dependent effects on intestinal epithelial cells,
promoting epithelial restitution in fibronectin-rich tissue and proliferation in
fibronectin-poor mucosa.
PMID- 17030188
TI - TUCAN (CARD8) genetic variants and inflammatory bowel disease.
AB - BACKGROUND & AIMS: The identification of the association between Crohn's disease
(CD) and NOD2 (CARD15) confirmed both the heritability of CD and highlighted the
role of the nuclear factor kappaB (NFkappaB) pathway in disease pathogenesis.
Other susceptibility loci exist. TUCAN (CARD8) is located beneath a CD peak of
linkage on chromosome 19q. TUCAN is expressed in the gut and is a negative
regulator of NFkappaB, making it an excellent candidate gene for gastrointestinal
inflammation. METHODS: Ten single nucleotide polymorphisms (SNP) across TUCAN
were genotyped in 365 controls, 372 patients with CD, and 373 patients with
ulcerative colitis. A diagnostic panel for CD was constructed using smoking
status and TUCAN, NOD2, IBD5, NOD1, and TNFSF15 data. RESULTS: We demonstrate
significant association between a TUCAN SNP and CD (OR 1.35, P = .0083). The
association was more pronounced with disease affecting sites other than the colon
(odds ratio, 1.52) and NOD2-negative CD (odds ratio, 1.50). Combination of these
data with smoking and NOD2, IBD5, NOD1, and TNFSF15 status demonstrated very
strong associations with CD and high sensitivities (96.3%), specificities
(99.4%), and likelihood ratios (12.8) for CD, although further work will be
needed before this model can be translated into direct clinical utility.
CONCLUSIONS: We have shown an association between a likely functional
polymorphism in TUCAN and CD. The combination of these data in a genetic panel
suggests that clinicians may soon be able to translate genetic advances into
direct benefits for patients.
PMID- 17030189
TI - CD36 is important for chylomicron formation and secretion and may mediate
cholesterol uptake in the proximal intestine.
AB - BACKGROUND & AIMS: Studies are aimed to determine the role of CD36 in intestinal
lipid absorption. METHODS: Knock-out (KO) and wild-type (WT) lymph fistula mice
were used to study fatty acids (FA) and cholesterol uptake, and chylomicron
formation and secretion. Uptake of FA and cholesterol was studied by using
sucrose polybehenate and fecal dual isotope methods, respectively. RESULTS: The
CD36 KO exhibited significant accumulation of dietary cholesterol in the
intestinal lumen at the end of 6-hour lipid infusion and significant reduction of
dietary cholesterol transport into the lymph. Fecal dual isotope studies,
however, did not show any significant difference in cholesterol uptake,
suggesting that given sufficient time, the KO intestine could compensate for the
reduced cholesterol uptake observed in the acute lymph fistula studies. Recovery
of dietary FA in the intestinal lumen was comparable between WT and KO,
consistent with the sucrose polybehenate study. However, the KO mice accumulated
more, albeit not significantly, dietary triacylglycerols in the intestine,
followed by a significant reduction in lymphatic transport. The ratio of
intestinal dietary triacylglycerols to FA was not higher in WT than KO, arguing
against impaired lipid esterification. It is rather a deficiency in the formation
and secretion of chylomicrons, as supported by the significantly less
apolipoprotein B-48 and the smaller, albeit not significantly, lipoprotein
particles secreted into the lymph of the KO. CONCLUSIONS: CD36 may play an
important role in chylomicron formation and secretion and may also facilitate
cholesterol uptake in the proximal intestine.
PMID- 17030190
TI - Loss of Raf kinase inhibitor protein promotes cell proliferation and migration of
human hepatoma cells.
AB - BACKGROUND & AIMS: The Raf kinase inhibitor protein (RKIP) has been identified as
a suppressor of the mitogen-activated protein kinase (MAPK) pathway. Loss of RKIP
function promotes tumor metastasis in prostate cancer and melanoma. The insulin
like growth factor I (IGF-I)-mediated MAPK cascade is often activated in
hepatocellular carcinoma (HCC), but the role of RKIP in the molecular
pathogenesis of these tumors is unknown. This study was performed to evaluate the
role of RKIP in the development of HCC. METHODS: The levels of RKIP expression in
HCC tumor and corresponding peritumoral tissues were determined by
immunohistochemistry and Western blot analysis. The underlying mechanisms of RKIP
were assessed with immunoblot analysis, Raf kinase activity assay, cell
proliferation, and migration assays after either overexpression or knockdown of
RKIP expression in HCC cell lines. RESULTS: RKIP expression is down-regulated in
human HCC compared with adjacent peritumoral tissues. Low RKIP levels were
correlated with enhanced extracellular signal-regulated-kinase (ERK)/MAPK pathway
activation. Reconstitution experiments antagonized IGF-I-mediated MAPK pathway
activation, resulting in reduced nuclear accumulation of phospho-ERK. In
contrast, knockdown of RKIP expression using small interfering RNA induced
activation of the ERK/MAPK pathway. Ectopic expression of RKIP altered HCC cell
proliferation and migration. CONCLUSIONS: Our findings indicate that down
regulation of RKIP expression is a major factor in activation of the IGF
I/ERK/MAPK pathway during human hepatocarcinogenesis.
PMID- 17030191
TI - Prickle-1 negatively regulates Wnt/beta-catenin pathway by promoting Dishevelled
ubiquitination/degradation in liver cancer.
AB - BACKGROUND & AIMS: Aberrant activation of Wnt signaling due to accumulation of
beta-catenin has been linked to tumorigenesis. Mutations of beta-catenin, APC,
and axins are important but not frequent enough to be accountable for the
accumulation of beta-catenin in human hepatocellular carcinoma (HCC). In this
study, we characterized the roles of Prickle-1, a Dishevelled (Dvl)-associated
protein, in regulation of Wnt/beta-catenin activity in HCC. METHODS: The
expression levels of human Prickle-1 and Dvl3 were examined in HCC cell lines and
human HCC samples. The interaction and effects of Prickle-1 on Dvl3, the Wnt/beta
catenin pathway, and cell growth were assessed in HCC cell lines. RESULTS: We
showed that Prickle-1 bound with Dvl3 and facilitated Dvl3
ubiquitination/degradation, and this was through its destruction box (D-box)
motifs. Enforced expression of Prickle-1 significantly reduced the Wnt/beta
catenin activity and tumorigenic properties of HCC cells. Clinicopathologic
analysis showed that underexpression of Prickle-1 was significantly associated
with overexpression of Dvl3, beta-catenin accumulation (P = .023), and larger
tumor size (P = .030). CONCLUSIONS: Our results have elucidated a novel
mechanistic relationship between Prickle-1 and Dvl3 in the Wnt/beta-catenin
pathway. The facilitation of Prickle-1 on Dvl3 degradation and the suppression of
beta-catenin activity and cell growth suggest that Prickle-1 is a negative
regulator of the Wnt/beta-catenin signaling pathway and is a putative tumor
suppressor in human HCCs.
PMID- 17030192
TI - Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP
sensitive K+ channel activity.
AB - BACKGROUND & AIMS: Changes in mitochondrial energy metabolism promoted by
uncoupling proteins (UCPs) are often found in metabolic disorders. We have
recently shown that hypertriglyceridemic (HTG) mice present higher mitochondrial
resting respiration unrelated to UCPs. Here, we disclose the underlying mechanism
and consequences, in tissue and whole body metabolism, of this mitochondrial
response to hyperlipidemia. METHODS: Oxidative metabolism and its response to
mitochondrial adenosine triphosphate (ATP)-sensitive K+ channel (mitoK(ATP))
agonists and antagonists were measured in isolated mitochondria, livers, and
mice. RESULTS: Mitochondria isolated from the livers of HTG mice presented
enhanced respiratory rates compared with those from wild-type mice. Changes in
oxygen consumption were sensitive to adenosine triphosphate (ATP), diazoxide, and
5-hydroxydecanoate, indicating they are attributable to mitochondrial ATP
sensitive K+ channel (mitoK(ATP)) activity. Indeed, mitochondria from HTG mice
presented enhanced swelling in the presence of K+ ions, sensitive to mitoK(ATP)
agonists and antagonists. Furthermore, mitochondrial binding to fluorescent
glibenclamide indicates that HTG mice expressed higher quantities of mitoK(ATP).
The higher content and activity of liver mitoK(ATP) resulted in a faster
metabolic state, as evidenced by increased liver oxygen consumption and higher
body CO(2) release and temperature in these mice. In agreement with higher
metabolic rates, food ingestion was significantly larger in HTG mice, without
enhanced weight gain. CONCLUSIONS: These results show that primary hyperlipidemia
leads to an elevation in liver mitoK(ATP) activity, which may represent a
regulated adaptation to oxidize excess fatty acids in HTG mice. Furthermore, our
data indicate that mitoK(ATP), in addition to UCPs, may be involved in the
control of energy metabolism and body weight.
PMID- 17030193
TI - Acetaldehyde inhibits PPARgamma via H2O2-mediated c-Abl activation in human
hepatic stellate cells.
AB - BACKGROUND & AIMS: Accumulating evidence indicates that acetaldehyde (AcCHO) is
one of the main mediators of fibrogenesis in alcoholic liver disease. AcCHO
stimulates synthesis of fibrillar collagens in hepatic stellate cells, but the
molecular events directly involved in the activation of collagen genes are
debatable. METHODS: Peroxisome proliferator-activated receptor gamma (PPARgamma)
is a nuclear receptor that is expressed in stellate cells, and its activation by
specific ligands inhibits collagen synthesis. In this study, we evaluated the
effects of AcCHO on PPARgamma transcriptional activity and its correlation with
the AcCHO-induced collagen synthesis in hepatic stellate cells. RESULTS: AcCHO
treatment inhibited ligand-dependent and -independent PPARgamma transcriptional
activity, and this effect was correlated with an increased phosphorylation of a
mitogen-activated protein kinase site at serine 84 of the human PPARgamma.
Transfection of the PPARgammaSer84Ala mutant completely prevented the effect of
AcCHO on PPARgamma activity and in parallel abrogated the induction of collagen
gene expression by AcCHO. The effect of AcCHO on PPARgamma activity and
phosphorylation was blocked by extracellular signal-regulated kinase (ERK) 1/2
and protein kinase C (PKC)delta inhibitors as well as by catalase, suggesting
that hydrogen peroxide is involved in the molecular cascade responsible for
PPARgamma phosphorylation via activation of the PKCdelta/ERK pathway.
Furthermore, inhibition of c-Abl completely abrogated the effect of AcCHO on
either PPARgamma function or collagen synthesis; in addition, expression of the
PPARgammaSer84Ala mutant prevented the profibrogenic signals mediated by c-Abl
activation. CONCLUSIONS: Our results showed that the induction of collagen
expression by AcCHO in stellate cells is dependent on PPARgamma phosphorylation
induced by a hydrogen peroxide-mediated activation of the profibrogenic c-Abl
signaling pathway.
PMID- 17030194
TI - Selection of a multiple drug-resistant hepatitis B virus strain in a liver
transplanted patient.
AB - BACKGROUND & AIMS: Sequential anti-hepatitis B virus (HBV) therapy may lead to
the selection of complex mutants. We analyzed the genetic and phenotypic
evolution of the viral quasispecies of a patient who received successively
lamivudine, add-on adefovir+lamivudine, followed by lamivudine+adefovir+hepatitis
B immunoglobulins (HBIg) after orthotopic liver transplantation. METHODS: For
genotypic analysis, a 1310-bp region of the polymerase gene was amplified,
cloned, and sequenced. Huh-7 cells were transfected to compare the replication
fitness of HBV mutants and their susceptibility to drugs. RESULTS: At baseline,
all HBV genomes carried a wild-type (wt) RT gene but 22% harbored the sP120S and
55% the sC107stop mutations within the surface (S) gene associated with vaccine
escape. Following viral breakthrough to lamivudine monotherapy, a complex mixture
of lamivudine-resistant HBV strains prevailed. Interestingly, among these mutants
emerged a population harboring only the rtL180M+A181V mutations, conferring
lamivudine-resistance in vitro. After addition of adefovir to the ongoing
treatment, viral load dropped, and the patient underwent an orthotopic liver
transplantation and received HBIg. As viral load rose again, a single viral
population was progressively selected, harboring the rtV173L+L180M+A181V+N236T
and sP120S mutations. In vitro, this last mutant showed a level of replication
reduced by only 30% compared to wt HBV and a strong resistance to both lamivudine
(>1000-fold) and adefovir (>10-fold). It remained sensitive to tenofovir both in
vitro and in vivo. CONCLUSIONS: We report the selection of a complex HBV mutant
that escaped the antiviral pressure of lamivudine, adefovir, and HBIg, and
provide insight on the process of selection via genotypic and phenotypic
analysis.
PMID- 17030195
TI - A tumor progression model for hepatocellular carcinoma: bioinformatic analysis of
genomic data.
AB - BACKGROUND & AIMS: It is widely recognized that genomic abnormalities underpin
the development of human cancers. Aberrant patterns of chromosomal changes may
represent useful information that can be used in classifying the complex traits
of liver cancer cases for the genetic events involved in tumor carcinogenesis,
tumor progression, and prognosis. METHODS: Genome-wide chromosomal aberrations of
158 hepatitis B virus-associated hepatocellular carcinoma (HCC) were studied by
comparative genomic hybridization (CGH). By application of a self-organizing tree
algorithm, statistically significant CGH events were used to construct an
evolutionary tree that could infer patient subgroups with different degrees of
tumor progression. The key CGH events in the subgroups were identified. The
clinical significance of the groupings and the key CGH events were examined.
RESULTS: Based on the patterns of significant chromosomal aberrations derived, 3
HCC subgroups organized in an evolutionary tree were identified. The groupings
possessed information reflecting the degrees of tumor progression, including
numbers of chromosomal aberrations, tumor stages, tumor sizes, and disease
outcome. Gains of 1q21-23 and 8q22-24 were identified as genomic events
associated with the early development of HCC. Gain of 3q22-24, however, was
identified as 1 of the late genomic events found to be associated with tumor
recurrence and poor overall patient survival. CONCLUSIONS: A tumor progression
model for HCC was constructed and revealed chromosomal imbalances that were
significantly associated with clinical pathologic characteristics of the disease.
This model explains a significant part of the variations in clinical outcome
among HCC patients.
PMID- 17030196
TI - Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and
pancreatic cancer: a meta-analysis.
AB - BACKGROUND & AIMS: Increasing evidence suggests that a low folate intake and
impaired folate metabolism may be implicated in the development of
gastrointestinal cancers. We conducted a systematic review with meta-analysis of
epidemiologic studies evaluating the association of folate intake or genetic
polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), a central
enzyme in folate metabolism, with risk of esophageal, gastric, or pancreatic
cancer. METHODS: A literature search was performed using MEDLINE for studies
published through March 2006. Study-specific relative risks were weighted by the
inverse of their variance to obtain random-effects summary estimates. RESULTS:
The summary relative risks for the highest versus the lowest category of dietary
folate intake were 0.66 (95% confidence interval [CI], 0.53-0.83) for esophageal
squamous cell carcinoma (4 case-control), 0.50 (95% CI, 0.39-0.65) for esophageal
adenocarcinoma (3 case-control), and 0.49 (95% CI, 0.35-0.67) for pancreatic
cancer (1 case-control, 4 cohort); there was no heterogeneity among studies.
Results on dietary folate intake and risk of gastric cancer (9 case-control, 2
cohort) were inconsistent. In most studies, the MTHFR 677TT (variant) genotype,
which is associated with reduced enzyme activity, was associated with an
increased risk of esophageal squamous cell carcinoma, gastric cardia
adenocarcinoma, noncardia gastric cancer, gastric cancer (all subsites), and
pancreatic cancer; all but one of 22 odds ratios were >1, of which 13 estimates
were statistically significant. Studies of the MTHFR A1298C polymorphism were
limited and inconsistent. CONCLUSIONS: These findings support the hypothesis that
folate may play a role in carcinogenesis of the esophagus, stomach, and pancreas.
PMID- 17030197
TI - Will screening colonoscopy disappear and transform gastroenterology practice?
Threats to clinical practice and recommendations to reduce their impact: report
of a consensus conference conducted by the AGA Institute Future Trends Committee.
AB - The AGA Institute Future Trends Committee (FTC) developed this report based on a
consensus conference it convened on April 1-2, 2006, in Washington, DC. The
report was prepared for the FTC by Carol Regueiro, MD, a medical writer under
contract to the AGA Institute, and Michael Stolar, PhD, staff liaison to the FTC.
It was approved by the FTC on July 12, 2006, and accepted by the AGA Institute
Governing Board on July 22, 2006. This report reflects the panel's assessment of
information available at the time of the conference. Readers should view this
report in the context of data that will continue to accumulate and facts that may
change after its creation.
PMID- 17030198
TI - AGA Institute medical position statement on the use of endoscopic therapy for
gastroesophageal reflux disease.
AB - This document presents the official recommendations of the AGA Institute on
"Endoscopic Therapy for Gastroesophageal Reflux Disease." It was approved by the
Clinical Practice and Economics Committee on June 20, 2006, and by the AGA
Institute Governing Board on July 24, 2006.
PMID- 17030199
TI - AGA Institute technical review on the use of endoscopic therapy for
gastroesophageal reflux disease.
PMID- 17030200
TI - Abdominal distention: old hypotheses and new concepts.
PMID- 17030201
TI - Use of ribavirin in patients with chronic HCV genotype 1: when enough is really
enough.
PMID- 17030202
TI - Adding fuel to the fire: STAT3 priming of gastric tumorigenesis.
PMID- 17030203
TI - Genomic decoding of hepatocellular carcinoma.
PMID- 17030212
TI - Acetaminophen protein adducts: is acetaminophen to blame?
PMID- 17030215
TI - Adenoma or carcinoma: an important but difficult distinction.
PMID- 17030216
TI - Steroid-independent Crohn's disease patients also benefit from combination
therapy of infliximab plus azathioprine.
PMID- 17030218
TI - Clinical approach to the prostate: an update.
AB - Prostatic disease continues to present clinicians with challenges. Although giant
strides have been made in the medical and surgical management of benign prostatic
hyperplasia, many fundamental questions about its pathogenesis, progression, and
treatment efficacy remain unanswered. Prostate cancer also continues to be an
area in which progress is needed despite major recent advancements. Numerous
debates that include the value of prostate-specific antigen screening and
appropriate roles for each of the numerous therapeutic modalities await
resolution. For millions of patients who suffer from prostatitis, a major
breakthrough is yet to come. Current treatment regimens for prostatitis remain
ineffective at best. Contemporary approaches to the pathogenesis, diagnosis, and
treatment of benign prostatic hyperplasia, prostate cancer, and prostatitis are
discussed in this review.
PMID- 17030219
TI - Inflammatory disorders of the prostate and the distal genital tract.
AB - Inflammatory disease of the prostate and distal genital tract is emerging as a
major health problem because it is estimated that up to 15% of adult men may be
affected at some point in their lives. Clinically, the diagnosis of "prostatitis"
refers to multiple disorders that cause pelvic pain and discomfort, ranging from
acute bacterial infection to complex conditions that may not necessarily be
caused by prostatic inflammation. Because the traditional etiology-based
classification system did not always correlate with symptoms and therapeutic
efficacy, a new classification of prostatitis has been suggested by the National
Institutes of Health. New imaging techniques such as high-resolution transrectal
ultrasonography (TRUS) and MR imaging provide exquisite anatomic detail and often
play a crucial role in the evaluation of these patients.
PMID- 17030220
TI - Transrectal sonography in prostate evaluation.
AB - Prostate cancer is the most prevalent newly diagnosed noncutaneous malignancy in
men. With the continued use of prostate-specific antigen screening, there has
been a dramatic rise in the number of prostate biopsied performed. Transrectal
ultrasonography (TRUS) is an essential tool used for detecting prostate pathology
and performing prostate biopsies. This article review the indications and
principles of TRUS of the prostate, the technique of TRUS, and controversies
pertaining to prostate core biopsy.
PMID- 17030221
TI - Benign prostatic hyperplasia: a review and ultrasound classification.
AB - Benign prostatic hyperplasia (BPH) is reviewed, including definition,natural
history, diagnosis, and brief discussion of clinical management. Transrectal
ultrasound is used to demonstrate the gross anatomy and natural history of BPH
and its role in diagnosis and treatment strategies. A potentially useful
ultrasound classification of BPH based on the gross anatomic classification of
Randall is illustrated.
PMID- 17030222
TI - Prostate cancer imaging--what the urologic oncologist needs to know.
AB - Appropriate imaging for prostate cancer patients depends on the clinical disease
state of the patient and the question being asked. For patients who do not have a
cancer diagnosis, ultrasound is the standard approach, in combination with a
sextant biopsy. In the future, contrast-enhanced ultrasound and MR imaging
directed biopsy may improve biopsy yield and decrease biopsy number. For
clinically localized disease, endorectal coil MR imaging and bone scanning may
play a role in patients who have risk factors for extracapsular extension, but
more data are needed to define the role of MR spectroscopy and lymphtrophic
nanoparticle MR imaging. In the rising prostate-specific antigen (PSA) setting
after definitive local therapy, endorectal coil MR imaging may help define local
recurrence, whereas bone scanning can be useful in the setting of higher PSA or
rapid PSA velocity.
PMID- 17030223
TI - MR imaging and MR spectroscopy in prostate cancer management.
AB - Currently, endorectal coil MR imaging has the ability to improve accuracy in
staging of localized prostate cancer. The addition of MR spectroscopic imaging
has further improved the sensitivity of MR imaging for intraprostatic tumor
localization. Additional refinements and techniques are expected to further
improve the performance of MR imaging for prostate cancer imaging and to aid in
patient management. Further studies are required to identify the ideal role for
MR imaging in the diagnosis and management of prostate cancer.
PMID- 17030224
TI - Image-guided brachytherapy for prostate cancer.
AB - Prostate brachytherapy offers and effective treatment for organ-confined prostate
carcinoma. It is rapidly delivered compared with external beam radiation therapy
or surgery and well tolerated by patients. Volumetric imaging and image guidance
play critical roles in patient selection, treatment planning, treatment delivery,
and postimplant assessment. Costs, availability and ease of use often dictate the
local and regional differences in imaging approach, whether ultrasound, CT, or
MR. Future volumetric image developments may permit multimodality image fusion to
integrate tumor-specific imaging such as MR spectroscopy or positron emission
tomography/CT into real-time ultrasound, CT, or MR.
PMID- 17030225
TI - Imaging the pediatric prostate.
AB - The prostate gland is not often the target of imaging in children but may be
imaged during investigation of symptoms related to the lower genitourinary tract
such as hematuria, urinary retention, dysuria, and incontinence or during an
evaluation for suspected congenital anomalies. Ultrasound and voiding
cystourethrography are useful for initial evaluation of congenital and neoplastic
disorders of the prostate. MR imaging and CT are useful in delineating more
detailed anatomy before surgical planning and in determining the organ of origin
in a patient who has a large pelvic mass.
PMID- 17030227
TI - Clinical and pathologic perspectives on aspirin sensitivity and asthma.
AB - Aspirin and other nonsteroidal anti-inflammatory drugs that inhibit COX-1 induce
unique nonallergic reactions, consisting of attacks of rhinitis and asthma. These
hypersensitivity reactions occur in a subset of asthmatic subjects, thus
identifying them as having this exclusive clinical presentation. We refer to
these patients as having aspirin-exacerbated respiratory disease, a disease
process that produces devastating eosinophilic inflammation of both the upper and
lower respiratory tracts. This review focuses on a description of patients with
aspirin-exacerbated respiratory disease, methods available to diagnose their
condition, the unique ability of all nonsteroidal anti-inflammatory drugs that
inhibit COX-1 to cross-react with aspirin, an update on pathogenesis, and current
thoughts about treatment.
PMID- 17030228
TI - The role of leukotrienes in airway inflammation.
AB - Cysteinyl leukotrienes (cysLTs) are a class of closely structurally related lipid
molecules, originally described as slow-reacting substance of anaphylaxis, with a
myriad of biologic functions. These activities include producing smooth muscle
contraction and mucus secretion, recruiting allergic inflammatory cells,
modulating cytokine production, influencing neural transmission, and altering
structural changes in the airway. Administration of cysLTs to animals and human
subjects reproduces many features of allergic inflammation and asthma.
Leukotriene (LT) blockers have independent efficacy in asthma and improve
pulmonary function when added to inhaled steroids. Conversely, blockade of this
pathway both in animals and in human subjects results in important reductions in
inflammation and its consequences and might reduce structural changes of
remodeling. These data collectively make a compelling case for an important role
of cysLTs in airway inflammation and asthma. However, the magnitude of effect of
anti-LTs is smaller than that of corticosteroids, and there is more variability
in benefit of LT blockade than is seen with inhaled steroids. In addition, adding
anti-LTs to inhaled steroids in asthmatic patients does not appear to produce
added anti-inflammatory benefit. Genetic polymorphisms and environmental factors,
such as tobacco smoke exposure, might underlie some of the heterogeneity of
response to LT blockers.
PMID- 17030229
TI - Selection of patients for aspirin desensitization treatment.
PMID- 17030230
TI - Mild persistent asthma: is any treatment needed?
AB - Asthma treatment guidelines are intended to relieve symptoms and to prevent
complications such as exacerbations, airway remodeling, and death. The existing
recommendations are based on a combination of evidence and expert opinion. Recent
data raise questions about the need for chronic controller therapy for those
patients at the very low end of the asthma-severity continuum. Although these
data are not sufficient to warrant a change in guidelines, the new information
points out the need for large, long-term studies on the treatment of mild
persistent asthma, with an emphasis on exacerbations, remodeling, and the
relationship between these outcomes and markers of asthma control.
PMID- 17030231
TI - Salmeterol response is not affected by beta2-adrenergic receptor genotype in
subjects with persistent asthma.
AB - BACKGROUND: Recent studies suggest that there might be an association between
albuterol use and worsening asthma in patients homozygous for arginine (Arg/Arg)
at codon 16 of the beta-receptor. However, it is not known whether similar
responses occur in Arg/Arg patients receiving long-acting beta2-agonists.
OBJECTIVE: We sought to evaluate the effects of variation in the beta2-adrenergic
receptor gene (ADRB2) on clinical response to salmeterol administered with
fluticasone propionate. METHODS: Subjects (n = 183) currently receiving short
acting beta2-agonists were randomized to twice-daily therapy with salmeterol, 50
microg, administered with fluticasone propionate, 100 microg, in a single inhaler
or daily therapy with montelukast for 12 weeks, followed by a 2- to 4-day run-out
period. RESULTS: There was sustained and significant improvement (P < .001) over
baseline in all measures of asthma control in subjects receiving salmeterol,
regardless of Arg16Gly genotype. Morning peak expiratory flow in subjects with
the Arg/Arg genotype showed 89.0 +/- 16.1 L/min improvement over baseline
compared with 93.7 +/- 12.7 L/min for Gly/Gly subjects and 92.5 +/- 11.9 L/min
for Arg/Gly subjects. Pairwise changes were similar for Arg/Arg compared with
Gly/Gly or Arg/Gly genotypes (estimated differences, 4.7 L/min and 3.5 L/min,
respectively). Responses did not appear to be modified by haplotype pairs. During
the run-out period, all subjects had predictable and similar decreases in
measures of asthma control, with no differences between genotypes. CONCLUSION:
Response to salmeterol does not vary between ADRB2 genotypes after chronic dosing
with an inhaled corticosteroid. CLINICAL IMPLICATIONS: Analyses from this study
indicate that genetic polymorphisms leading to Arg16Gly sequence changes within
the beta2-adrenergic receptor do not affect patients' responses to recommended
asthma therapy with salmeterol and fluticasone propionate.
PMID- 17030232
TI - Buffering airway acid decreases exhaled nitric oxide in asthma.
AB - BACKGROUND: The human airway is believed to be acidified in asthma. In an acidic
environment nitrite is converted to nitric oxide (NO). OBJECTIVE: We hypothesized
that buffering airway lining fluid acid would decrease the fraction of exhaled NO
(F(ENO)). METHODS: We treated 28 adult nonsmoking subjects (9 healthy control
subjects, 11 subjects with mild intermittent asthma, and 8 subjects with
persistent asthma) with 3 mL of 10 mmol/L phosphate buffered saline (PBS) through
a nebulizer and then serially measured F(ENO) levels. Six subjects also received
PBS mouthwash alone. RESULTS: F(ENO) levels decreased after buffer inhalation.
The maximal decrease occurred between 15 and 30 minutes after treatment; F(ENO)
levels returned to pretreatment levels by 60 minutes. The decrease was greatest
in subjects with persistent asthma (-7.1 +/- 1.0 ppb); this was more than in
those with either mild asthma (-2.9 +/- 0.3 ppb) or healthy control subjects (
1.7 +/- 0.3 ppb, P < .001). Levels did not decrease in subjects who used PBS
mouthwash. CONCLUSION: Neutralizing airway acid decreases F(ENO) levels. The
magnitude of this change is greatest in persistent asthma. These data suggest
that airway pH is a determinant of F(ENO) levels downstream from NO synthase
activation. CLINICAL IMPLICATIONS: Airway biochemistry modulates F(ENO) levels.
For example, nitrite is converted to NO in the airway, particularly the inflamed
airway, by means of acid-based chemistry. Thus airway pH should be considered in
interpreting clinical F(ENO) values. In fact, PBS challenge testing integrates
airway pH and F(ENO) analysis, potentially improving the utility of F(ENO) as a
noninvasive test for the type and severity of asthmatic airway inflammation.
PMID- 17030233
TI - Preterm delivery and asthma: a systematic review and meta-analysis.
AB - BACKGROUND: Accumulating evidence suggests that reduced duration of pregnancy
predicts increased risk of asthma, but the studies published have been
inconsistent. OBJECTIVE: We sought to synthesize the evidence on the relation
between preterm delivery and the risk of asthma later in life and to assess
differences between the studies as potential sources for heterogeneity of the
results. METHODS: We conducted a MEDLINE search (until the end of May 2005). The
outcome was asthma. The determinant of interest was preterm delivery defined as a
gestational age of less than 37 weeks. RESULTS: We identified 19 articles that
provided estimates for the meta-analysis. The summary effect estimates for asthma
(fixed-effects odds ratio, 1.074 [95% CI, 1.072-1.075]; heterogeneity P = .000;
random-effects odds ratio, 1.366 [95% CI, 1.303-1.432]) showed an increased risk
in relation to preterm delivery, with substantial heterogeneity between study
specific estimates. The effect of preterm delivery on asthma was stronger in
cross-sectional studies; studies with broad outcome criteria, a small sample
size, and a younger study population; and studies conducted in English-speaking
populations, outside Europe, and published more recently. In metaregression,
adjusting for other determinants, the effect estimate was significantly
associated only with the mean age of the study population. CONCLUSIONS: The
weight of evidence shows that preterm babies have an increased risk of asthma
compared with term babies. CLINICAL IMPLICATIONS: Recognition of prematurity as a
determinant of asthma emphasizes the importance of active treatment of
physiologic airflow obstruction and a need for special preventive measures
against known environmental determinants of asthma in preterm babies.
PMID- 17030234
TI - Ligation of intercellular adhesion molecule 3 induces apoptosis of human blood
eosinophils and neutrophils.
AB - BACKGROUND: Intercellular adhesion molecule 3 (ICAM-3) is highly expressed on
human granulocytes, including eosinophils and neutrophils, but the functions of
ICAM-3 in these cells are not well understood. OBJECTIVE: Our studies test the
hypothesis that ICAM-3 regulates granulocyte apoptosis. METHODS: Intercellular
adhesion molecule 3 was activated by a mAb that recognizes an ICAM-3 epitope that
binds its ligand, CD11a/CD18. In some experiments with eosinophils, recombinant
human IL-5 or GM-CSF was added to mimic in vivo antiapoptotic conditions.
Staining with annexin V-fluorescein isothiocyanate and propidium iodide
identified apoptotic cells. RESULTS: Binding of ICAM-3 increased apoptosis of
both eosinophils (18 and 48 hours) and neutrophils (18 hours). At 18 hours,
eosinophil apoptosis increased from 31.4% +/- 3.5 SE (IgG control) to 45.2% +/-
3.8 SE (anti-ICAM-3), and neutrophil apoptosis increased from 48% +/- 4.1 SE (IgG
control) to 55.3% +/- 4.5 SE (anti-ICAM-3). At 48 hours, eosinophil apoptosis
increased 2-fold under baseline conditions and also in the presence of
recombinant human IL-5 or GM-CSF. In both eosinophils and neutrophils, incubation
with a blocking antibody against CD18 integrins blunted ICAM-3-induced apoptosis.
In eosinophils, blocking peptides for caspases 8 and 9, proteases critical to
apoptosis, also decreased ICAM-3-induced apoptosis to control levels. CONCLUSION:
Through its effect on eosinophil and neutrophil apoptosis, ICAM-3 may be an
important anti-inflammatory molecule that can oppose the proinflammatory effects
of IL-5 and GM-CSF. CLINICAL IMPLICATIONS: These findings provide a mechanism for
apoptotic clearance of eosinophils and neutrophils involved in allergic
inflammation that, unlike necrosis, does not cause nonspecific tissue injury.
PMID- 17030235
TI - Fungal zymosan induces leukotriene production by human mast cells through a
dectin-1-dependent mechanism.
AB - BACKGROUND: Fungi are capable of causing or exacerbating inflammatory disease in
the airways. We have previously demonstrated that zymosan and peptidoglycan
induce the production of cysteinyl leukotrienes from human mast cells. However,
the mechanisms of pathogen-induced leukotriene production by immune effector
cells are very poorly understood. The coreceptor dectin-1, through a Syk tyrosine
kinase-dependent pathway, can mediate some responses to fungal challenge, but its
expression by mast cells and its involvement in lipid mediator responses have not
been assessed. OBJECTIVE: In the current study, the potential role of dectin-1 in
zymosan-induced leukotriene production from human mast cells was examined.
METHODS: Human mast cells were examined for dectin-1 mRNA and protein expression.
Human mast cells were incubated with either zymosan or peptidoglycan in the
presence or absence of specific inhibitors for dectin-1 or Syk tyrosine kinase
and mediator production examined. RESULTS: Human mast cells were found to express
a functional isoform of dectin-1. Both peptidoglycan and zymosan induced
significant amounts of leukotriene (LT)-B4 and LTC4. The dectin-1 inhibitors
laminarin and glucan phosphate reduced the LTC4 response to zymosan by more than
60% but did not alter peptidoglycan responses. Inhibitors of Syk tyrosine kinase
activity significantly decreased LTC4 production in response to both
peptidoglycan and zymosan. CONCLUSION: These data demonstrate mast cell
expression of the coreceptor dectin-1 and a role for this molecule in the
generation of cysteinyl leukotrienes. CLINICAL IMPLICATIONS: These findings
suggest new approaches to the selective inhibition of lipid mediator production
in response to fungal infection or exposure.
PMID- 17030236
TI - Subpollen particles: carriers of allergenic proteins and oxidases.
AB - BACKGROUND: Pollen is known to induce allergic asthma in atopic individuals,
although only a few inhaled pollen grains penetrate into the lower respiratory
tract. OBJECTIVE: We sought to provide evidence that subpollen particles (SPPs)
of respirable size, possessing both antigenic and redox properties, are released
from weed pollen grains and to test their role in allergic airway inflammation.
METHODS: The release of SPPs was analyzed by means of microscopic imaging and
flow cytometry. The redox properties of SPPs and the SPP-mediated oxidative
effect on epithelial cells were determined by using redox-sensitive probes and
specific inhibitors. Western blotting and amino acid sequence analysis were used
to examine the protein components of the SPP. The allergenic properties of the
SPP were determined in a murine model of experimental asthma. RESULTS: Ragweed
pollen grains released 0.5 to 4.5 microm of SPPs on hydration. These contained
Amb a 1, along with other allergenic proteins of ragweed pollen, and possessed
nicotinamide adenine dinucleotide (reduced) or nicotinamide adenine dinucleotide
phosphate (reduced) [NAD(P)H] oxidase activity. The SPPs significantly increased
the levels of reactive oxygen species (ROS) in cultured cells and induced
allergic airway inflammation in the experimental animals. Pretreatment of the
SPPs with NAD(P)H oxidase inhibitors attenuated their capacity to increase ROS
levels in the airway epithelial cells and subsequent airway inflammation.
CONCLUSIONS: The allergenic potency of SPPs released from ragweed pollen grains
is mediated in tandem by ROS generated by intrinsic NAD(P)H oxidases and
antigenic proteins. CLINICAL IMPLICATIONS: Severe clinical symptoms associated
with seasonal asthma might be explained by immune responses to inhaled SPPs
carrying allergenic proteins and ROS-producing NAD(P)H oxidases.
PMID- 17030237
TI - Gene-environment interactions with CD14 C-260T and their relationship to total
serum IgE levels in adults.
AB - BACKGROUND: Both endotoxin exposure and a single nucleotide polymorphism in one
of its receptors, CD14 C-260T, have been separately associated with total serum
IgE levels. Furred pets might also influence IgE levels through their effects on
endotoxin levels. However, how these factors interact to influence total IgE
levels is not well known, especially in adults. OBJECTIVE: We sought to
investigate the interactive relationship between endotoxin levels, pet exposure,
and CD14 C-260T genotype on total serum IgE levels in adults. METHODS: Mothers
enrolled in an ongoing cohort study were genotyped for the CD14 C-260T
polymorphism. Exposure to pets was assessed by using questionnaires and dust
allergen levels collected in the home. Endotoxin exposure was estimated by using
dust collected from mothers' bedroom floors. The primary outcome measure was
total serum IgE level. RESULTS: CD14 C-260T genotype was assessed in 517 (85.2%)
of the 607 women enrolled in the study. The CD14 C-260T genotype was
significantly associated with total IgE levels; however, this relationship
appeared to be modified by the level of endotoxin exposure. Similar interactions
between CD14 C-260T and pet exposure were not seen, regardless of the measure of
pet exposure used. CONCLUSIONS: The CD14 C-260T genotype and endotoxin exposure
together appear to influence total serum IgE levels in adults. The absence of a
similar gene-environment interaction for pet exposure suggests separate
mechanisms of action. CLINICAL IMPLICATIONS: A common polymorphism in the
endotoxin receptor, CD14 C-260T, and dust endotoxin levels in the home might
interact to influence total serum IgE levels into adulthood.
PMID- 17030238
TI - IL-13 receptor alpha 2: a regulator of IL-13 and IL-4 signal transduction in
primary human fibroblasts.
AB - BACKGROUND: IL-13 and IL-4 share many functional properties as a result of their
use of a common receptor complex comprising IL-13 receptor alpha 1 (IL-13Ralpha1)
and IL-4 receptor alpha (IL-4Ralpha). The nonsignaling receptor IL-13 receptor
alpha 2 (IL-13Ralpha2) binds IL-13 with high affinity and specificity and is
believed to be a decoy receptor for IL-13. OBJECTIVE: We sought to examine the
inhibitory effects of soluble and membrane-bound IL-13Ralpha2 on IL-13- and IL-4
mediated effects. METHODS: Primary human fibroblasts were grown from
endobronchial biopsy specimens obtained from volunteers. Upregulation of IL
13Ralpha2 mRNA was measured by means of RT-PCR, and the level of surface
expression was measured by means of FACS. RESULTS: We found that a recombinant
soluble form of IL-13Ralpha2 blocked the effects of IL-13, but not IL-4, in
fibroblasts in vitro. However, we found that the transmembrane form of IL
13Ralpha2 could attenuate both IL-13 and IL-4 responses, even though the response
to TNF-alpha was unaffected. Furthermore, we found that IL-13Ralpha2 became
associated with IL-4Ralpha in the presence of IL-4. Addition of a blocking
antibody to the extracellular domain of IL-13Ralpha2 restored responses of both
IL-13 and IL-4. CONCLUSION: The ability of IL-13Ralpha2 to regulate IL-4 was
previously unrecognized in primary airway cells. These data reveal a novel role
for IL-13Ralpha2 as a negative regulator of both IL-13 and IL-4 signaling in
human bronchial fibroblasts. CLINICAL IMPLICATIONS: It appears that IL-13Ralpha2
might be a powerful suppressor of TH2-mediated responses and thus represents a
potential therapeutic target for the treatment of asthma.
PMID- 17030240
TI - Hyperosmolar conjunctival provocation for the evaluation of nonspecific
hyperreactivity in healthy patients and patients with allergy.
AB - BACKGROUND: Tissue hyperreactivity of target organs to nonspecific stimuli is
known to be an important factor in influencing the clinical picture of allergic
disease. OBJECTIVE: To identify the sensitivity and specificity of a hyperosmolar
conjunctival provocation test in predicting conjunctival hyperreactivity and to
relate this reactivity to the presence of ocular discomfort in subjects with and
without allergy. METHODS: In 50 healthy patients and 19 patients with allergic
conjunctivitis during remission phase, symptoms of ocular discomfort triggered by
nonspecific stimuli were identified and graded with a discomfort score. Subjects
were then challenged with a glucose solution at increasing concentrations (from
10% to 50%). The glucose concentration that elicited 2+ conjunctival hyperemia
was considered the provoking dose. The response to this hyperosmolar provocation
in subjects with ocular discomfort was compared with that of asymptomatic
subjects. Sensitivity and specificity of the test in predicting conjunctival
hyperreactivity were analyzed. RESULTS: Six of 50 healthy subjects and 12 of 19
subjects with allergy complained of ocular discomfort after exposure to
nonspecific stimuli. The hyperosmolar provocation test discriminated between
subjects with and without ocular discomfort (mean provoking dose: 39.5% +/- 5%
and 47.5% +/- 5% glucose, respectively; P < .001). Forty percent glucose was the
optimal threshold dose that demonstrated the highest sensitivity and specificity
for prediction of conjunctival hyperreactivity. Discomfort scores were
significantly related to provoking dose values (P < .05). CONCLUSION: This study
provides a standardized procedure to detect nonspecific conjunctival
hyperreactivity independent of underlying atopy. CLINICAL IMPLICATIONS:
Hyperosmolar provocation test may be useful for identifying conjunctival
hyperreactivity in subjects with and without allergy with a history of ocular
discomfort.
PMID- 17030239
TI - Filaggrin loss-of-function mutations predispose to phenotypes involved in the
atopic march.
AB - BACKGROUND: Childhood eczema often precedes the development of asthma and
allergic rhinitis in the so-called atopic march. Recently, 2 loss-of-function
mutations in the gene encoding the epidermal barrier protein filaggrin were
reported to be predisposing factors for eczema and concomitant asthma, suggesting
a possible role in disease transition. OBJECTIVE: We aimed to assess the
importance of filaggrin loss-of-function mutations in the susceptibility to
eczema and associated clinical phenotypes. METHODS: The filaggrin mutations were
genotyped and tested for association with allergic disorders in 2 large European
populations including 1092 children with eczema. RESULTS: Highly significant
association of the filaggrin null mutations with eczema and concomitant asthma
was replicated. Moreover, we found that these mutations predispose to asthma,
allergic rhinitis, and allergic sensitization only in the presence of eczema. We
show that the presence of 2 filaggrin null alleles is an independent risk factor
for asthma in children with eczema, and that the 2 investigated mutations account
for about 11% of eczema cases in the German population. CONCLUSION: These results
lend strong support to the role of filaggrin in the pathogenesis of eczema and in
the subsequent progression along the atopic march. The fact that previous
expression of eczema is a prerequisite for the manifestation of allergic airways
disease and specific sensitization highlights the importance of the epidermal
barrier in the pathogenesis of these disorders. CLINICAL IMPLICATIONS: Our
results suggest that the maintenance and repair of the epidermal barrier in
infants with eczema may prevent the subsequent development of allergic airways
disease.
PMID- 17030241
TI - Purification of a novel aminopeptidase from the pollen of Parietaria judaica that
alters epithelial integrity and degrades neuropeptides.
AB - BACKGROUND: Parietaria judaica pollen is a common cause of pollinosis in the
Mediterranean area. OBJECTIVE: This study sought to purify and characterize the
peptidase responsible for the majority of proteolytic activity present in the
pollen extract of P judaica, and to investigate its contribution to the allergic
response. METHODS: A serial of chromatographic steps was applied to isolate the
peptidase from P judaica's pollen, and its biochemical properties were
determined. Bioactive peptides present in the airways were incubated with the
peptidase, and their degradation was visualized by direct protein sequencing. In
addition, we measured the cellular detachment, by methylene blue binding assay,
of an airway-derived epithelial cell line (A549) in the presence of the
peptidase, and visualized, by Western blot, the degradation of proteins from
intercellular junctions. RESULTS: We purified a 98-kDa peptidase from the pollen
of P judaica that was classified as an aminopeptidase on the basis of its
biochemical properties and internal amino acid sequence. The aminopeptidase was
able to degrade bioactive peptides. Moreover, the aminopeptidase caused cellular
detachment of A549 cell line and degradation of occludin and E-cadherin.
CONCLUSION: Our results suggest that the P judaica aminopeptidase can alter the
integrity of the epithelium barrier by degrading occludin as well as E-cadherin.
In addition, P judaica aminopeptidase can degrade bioactive peptides, which can
exacerbate the overall bronchoconstrictive effect detected in asthmatic lungs.
CLINICAL IMPLICATIONS: The novel aminopeptidase described here could constitute a
relevant therapeutic target in the treatment of allergic disorders induced by the
pollen of P judaica.
PMID- 17030242
TI - Biophysical determinants of toluene diisocyanate antigenicity associated with
exposure and asthma.
AB - BACKGROUND: Toluene diisocyanate (TDI), a widely used aromatic diisocyanate with
the potential to cause asthma, reacts with albumin in the airway fluid, which
acts as a carrier protein for chemical presentation to the immune system.
Structural elucidation of TDI-albumin conjugates is crucial to understanding the
human immune response to TDI exposure. OBJECTIVE: Investigate the dependence of
TDI's antigenicity on the biophysics of exposure and its association with TDI
asthma. METHODS: Toluene diisocyanate-albumin conjugates were generated by
exposing albumin to TDI in liquid or vapor phase (liquid or vapor TDI-albumin,
respectively). Conjugates were characterized by native gel electrophoresis and
matrix-assisted laser desorption/ionization-mass spectrometry, and used as
antigens in ELISA assays for serum specific-IgE and IgG. RESULTS: The physical
phase of TDI (vapor vs liquid) affects the formation of TDI-albumin conjugates,
with measurable differences in the amount of TDI per albumin molecule, migration
in native gels, matrix-assisted laser desorption/ionization-mass spectrometry
mass/charge spectra, and antigenicity. Vapor TDI-albumin conjugates were
recognized by IgE from 44% of subjects with TDI asthma, whereas liquid TDI
albumin conjugates are recognized by IgE from only 17% of these patients. A
significant (P < .05) association between TDI exposure and vapor TDI-albumin
specific serum IgG was also observed. CONCLUSION: Biophysics of TDI exposure
substantially affects formation of TDI-albumin conjugates recognized by the
immune system in association with exposure and asthma. CLINICAL IMPLICATIONS: The
data suggest that serology may help identify TDI asthmatics and exposed workers
if the appropriate form of TDI is used as the antigenic basis for analysis.
PMID- 17030243
TI - Exposure to Alternaria alternata in US homes is associated with asthma symptoms.
AB - BACKGROUND: Exposure to the fungus Alternaria alternata is a risk factor for
asthma. Few studies have examined Alternaria exposures in indoor environments.
OBJECTIVE: We examined whether exposure to A alternata in US homes was associated
with asthma-related outcomes. METHODS: The data for this study were collected as
part of the National Survey of Lead and Allergens in Housing. This cross
sectional study surveyed a nationally representative sample of 831 housing units
inhabited by 2456 individuals in 75 different locations throughout the United
States. An interviewer-administered questionnaire obtained information on
demographics, household characteristics, and occupants' health status. Exposure
to A alternata was assessed by measuring concentrations of A alternata antigens
in vacuumed dust samples using a polyclonal anti-A alternata antibody assay. Dust
samples were collected from a bed, a sofa, or a chair, and from bedroom, living
room, and kitchen floors. RESULTS: Lifetime prevalence of doctor-diagnosed asthma
was 11.2%, and 6.9% of the study subjects reported active asthma symptoms in the
past 12 months. The prevalence of current symptomatic asthma increased with
increasing Alternaria concentrations in US homes; higher levels of A alternata
antigens increased the odds of having asthma symptoms in the past year (relative
to the lowest tertile, adjusted odds ratio was 1.52, 95% CI, 0.90-2.55 for the
2nd tertile; and 1.84, 95% CI, 1.18-2.85 for the 3rd tertile). CONCLUSION:
Exposure to A alternata in US homes is associated with active asthma symptoms.
CLINICAL IMPLICATIONS: Measures that reduce indoor exposure to A alternata may
help control asthma exacerbations.
PMID- 17030244
TI - Adherence and persistence with fluticasone propionate/salmeterol combination
therapy.
AB - BACKGROUND: Pharmacy database medication refill studies provide a panoramic view
of medication-taking behavior in patients nationally. OBJECTIVE: To investigate
fluticasone propionate/salmeterol combination (FSC) adherence, including the
factors associated with refill adherence in a large national pharmacy database.
METHODS: Adherence and persistence were documented for 12 months from date of
initial FSC prescription in 5504 patients who filled their medication at a
nationwide pharmacy chain. RESULTS: On average, patients filled enough medication
to cover 22.2% of days. More than half the patients filled a 30-day prescription
only once over the 1-year interval. Higher adherence levels were associated with
being male, being older than 35 years, having a comorbid disorder, a having a
copay of 1.01 dollar to 10 dollars, previous beta2-agonist use, and a
prescription for higher-dose FSC. CONCLUSION: This pharmacy database study
portrays medication adherence levels to be considerably lower than those reported
in most clinical trials, suggests that most adults taking FSC obtain a single
fill before abandoning their controller medication, and indicates a need for a
reappraisal of current treatment guidelines and educational strategies for both
providers and patients. CLINICAL IMPLICATIONS: For many patients, filling of a
controller medication is markedly discrepant with practice guidelines.
Reappraisal of both the guidelines and strategies to implement them is in order.
PMID- 17030245
TI - Human subjects without peanut allergy demonstrate T cell-dependent, TH2-biased,
peanut-specific cytokine and chemokine responses independent of TH1 expression.
AB - BACKGROUND: Peanut allergy is a major cause of anaphylaxis. Regulation of immune
responses to peanut allergen, particularly why sensitization does not usually
progress to allergic reactions, is not well investigated. Most studies focus
exclusively on serologic responses and individuals with peanut allergy.
OBJECTIVE: We sought to determine the existence, prevalence, and nature of peanut
specific, T cell-dependent cytokine and chemokine responses of adults who eat
peanut without having symptoms. METHODS: We developed systems to examine specific
immunity in peanut-tolerant individuals who had (1) negative histories and
negative peanut skin test responses, (2) negative histories and positive peanut
skin test responses, and (3) clinically apparent peanut allergy. After primary
culture of PBMCs restimulated with whole peanut extract, we quantified responses
characteristic of TH1 (IFN-gamma and CXCL10) and TH2-like immunity (IL-5, IL-13,
CCL17, and CCL22) using ultrasensitive ELISAs. Antigen-presenting cell
costimulatory requirements (CD4, HLA-DR, CD80/86, and cytotoxic T lymphocyte
associated antigen 4 [CTLA4] Ig) were determined. RESULTS: T cell-dependent,
peanut-specific IL-5, IL-13, and CCL22 were common in peanut-tolerant
individuals, regardless of whether they had positive or negative skin test
responses. These were blocked by anti-CD4 and were dependent on CD28/CD86
costimulation. None of the 70 individuals studied had demonstrable IFN-gamma or
CXCL10 responses to peanut. All demonstrated TH1 and TH2 responses to the
ubiquitous recall antigen streptokinase. CONCLUSIONS: Qualitatively similar and
quantitatively increasing peanut-specific TH2 responses in the consistent absence
of putatively protective TH1 immunity were found in both peanut-tolerant
individuals and those with peanut allergy. CLINICAL IMPLICATIONS: The continuum
of responses between individuals with negative and individuals with positive skin
test results, rather than TH1 versus TH2 bias, might be important in peanut
allergy.
PMID- 17030246
TI - Cloning and characterization of profilin (Pru du 4), a cross-reactive almond
(Prunus dulcis) allergen.
AB - BACKGROUND: The identity of allergenic almond proteins is incomplete. OBJECTIVE:
Our objective was to characterize patient IgE reactivity to a recombinant and
corresponding native almond allergen. METHODS: An almond cDNA library was
screened with sera from patients with allergy for IgE binding proteins. Two
reactive clones were sequenced, and 1 was expressed. The expressed recombinant
allergen and its native counterpart (purified from unprocessed almond flour) were
assayed by 1-dimensional and 2-dimensional gel electrophoresis, dot blot, and
ELISA, and screened for cross-reactivity with grass profilin. RESULTS: The 2
selected clones encoded profilin (designated Pru du 4) sequences that differed by
2 silent mutations. By dot-blot analyses, 6 of 18 patient sera (33%) reacted with
the recombinant Pru du 4 protein, and 8 of 18 (44%) reacted with the native form.
ELISA results were similar. Almond and ryegrass profilins were mutually
inhibitable. Two-dimensional immunoblotting revealed the presence of more than 1
native almond profilin isoform. The strength of reactivity of some patients'
serum IgE differed markedly between assays and between native and recombinant
profilins. CONCLUSION: Almond nut profilin is an IgE-binding food protein that is
cross-reactive with grass pollen profilin and is susceptible to denaturation,
resulting in variable reactivity between assay types and between patients.
CLINICAL IMPLICATIONS: Serum IgE of nearly half of the tested patients with
almond allergy reacts with almond nut profilin. Because most patients also had
pollinosis, the well-known cross-reactivity between pollen and food profilins
could account for this pattern of reactivity.
PMID- 17030247
TI - The atopy patch test in the diagnostic workup of suspected food-related symptoms
in children.
AB - BACKGROUND: There is an increasing need to develop test instruments that make
oral food challenges superfluous. OBJECTIVE: We sought to study the utility of
atopy patch tests (APTs) in the diagnostic workup of food allergy. METHODS: We
investigated 437 children (median age, 13 months; 90% with atopic dermatitis)
referred for evaluation of suspected food allergy. Specific serum IgE (sIgE)
measurements, skin prick tests (SPTs), APTs, and controlled oral food challenges
were performed. RESULTS: We analyzed 873 oral challenges with cow's milk, hen's
egg, wheat, and/or soy. One thousand seven hundred single APTs were performed. As
a single parameter, the APTs showed the best specificity compared with sIgE
measurements, SPTs, or both. Combining the APT with either the SPT or sIgE
measurement resulted in improved sensitivity and specificity. Decision points for
sIgE measurement and for the SPT showed lower values when combined with a
positive APT result. Correctly bypassing an oral food challenge with combined
testing, including APTs, only between 0.5% and 7% (99% predicted probability) and
between 6% and 14% (using 95% predicted probability) of children would fulfill
the criteria for avoiding an oral food challenge. CONCLUSION: Although the
predictive capacity of the APT is improved when combined with sIgE measurement or
the SPT, oral food challenges become superfluous in only 0.5% to 14% of study
patients. In addition, the APT is time consuming and demands a highly experienced
test evaluator. CLINICAL IMPLICATIONS: For daily clinical practice, the APT adds
only a small predictive value to the standard SPT and sIgE measurement in the
diagnostic workup of suspected food-related symptoms in our study population.
PMID- 17030248
TI - Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and
allergic contact dermatitis.
AB - BACKGROUND: IL-31 is produced by activated T lymphocytes, preferentially by TH2
cells. Transgenic mice overexpressing IL-31 have a phenotype resembling allergic
dermatitis in human subjects. OBJECTIVE: We sought to evaluate the potential
importance of IL-31 in the pathogenesis of human T cell-mediated skin diseases.
METHODS: We analyzed total RNA taken from 149 skin biopsy specimens from patients
with atopic dermatitis (AD), allergic contact dermatitis (ACD), or psoriasis in
comparison with specimens taken from patients with healthy skin (n = 13) by using
quantitative real-time PCR for the expression of TH1/TH2 cytokines. RESULTS: We
found statistically increased mRNA levels of IL-31 in biopsy specimens taken from
patients with AD, irrespective of the severity of the disease and serum IgE
levels. Moreover, IL-31 mRNA levels were strongly increased in many biopsy
specimens taken from patients with ACD. However, no increased transcription of IL
31 could be detected in biopsy specimens taken from psoriatic plaques. A
comparison of mRNA levels of IL-31 with TH1 or TH2 cytokines demonstrates a
correlation of the expression of IL-31 with IL-4 and IL-13 but not with IFN
gamma. No significant increase of IL-31 receptor mRNA could be detected in any
disease, whereas the second receptor subunit of IL-31, the oncostatin M receptor,
seems to be enhanced transcribed in patients with psoriasis. CONCLUSION: IL-31
expression is not only increased in patients with AD but also in those with ACD,
2 pruritic skin disorders. In both types of eczema, expression of IL-31 is
associated with the expression of the TH2 cytokines IL-4 and IL-13. CLINICAL
IMPLICATIONS: IL-31 might contribute not only to the development of AD but also
to ACD-provoked skin inflammation.
PMID- 17030249
TI - Mumps resurgence in the United States.
AB - The recent mumps epidemic in the central United States has generated a large
amount of public concern. A total of 2597 mumps cases have been reported in the
United States in 11 states since January 1, 2006, representing a marked
resurgence of mumps in a single year. The majority of these recent cases have
occurred in college students age 18 to 25 years. Most were vaccinated with 2
doses of measles, mumps, and rubella-containing vaccines. Such outbreaks provide
an opportunity for clinicians to review the clinical presentation, diagnosis, and
morbidity of vaccine-preventable infections and also to review immunologic
mechanisms and practice guidelines that might contribute to poor vaccine
responses. A review of mumps is provided with discussion of potential mechanisms
for vaccine failure.
PMID- 17030250
TI - Direct evidence for a critical role of CD30 in the development of allergic
asthma.
AB - BACKGROUND: CD30 is a costimulatory molecule belonging to the TNF receptor
superfamily that is expressed on activated T and B cells. Several studies have
demonstrated a positive correlation between expression of CD30 or increased
levels of soluble CD30 and the development and severity of allergic diseases.
However, thus far, the evidence for a role of CD30 in allergic diseases, such as
asthma, is only indirect. OBJECTIVE: The aim of the study was to directly
investigate the role of CD30 in a murine asthma model. METHODS: CD30-deficient
(B6.129P2-Tnfrsf8(tm1Mak)/J) and wild-type (WT) mice were immunized to ovalbumin
(OVA) to induce an asthma-like phenotype and compared in our murine asthma model.
Moreover, CD30/CD30 ligand signaling was blocked in OVA-immunized WT animals by
using mAbs against CD30 receptor and its ligand, CD153. RESULTS: The absence of
CD30 in OVA-immunized CD30-deficient mice resulted in significantly reduced
airway inflammation, serum IgE levels, and TH2 cytokine levels. The same effect
was observed when CD30/CD153 signaling was blocked in OVA-immunized WT animals
with mAbs against CD30 or CD30 ligand. CONCLUSION: Our results directly
demonstrate that CD30/CD153 interaction plays an important role in the induction
of TH2 cell-mediated allergic asthma. CLINICAL IMPLICATIONS: These findings
provide evidence for a role of the costimulatory molecule CD30 in allergic
asthma.
PMID- 17030251
TI - Potential involvement of dendritic cells in delayed-type hypersensitivity
reactions to beta-lactams.
AB - BACKGROUND: Although the involvement of T cells in delayed reactions to drugs has
been studied, little is known about the interaction between the drug and the
antigen-presenting cells. Dendritic cells (DCs) are professional antigen
presenting cells essential for initiating T-cell responses. Their ability is
regulated in a process known as maturation, by which they modulate the effector
immune response. OBJECTIVES: We studied the role of DCs in subjects who had a
delayed-type hypersensitivity reaction to amoxicillin to assess the effect on the
pattern of maturation and determine the capacity of DCs to activate T
lymphocytes. METHODS: We examined the consequences of the interaction between
monocyte-derived DCs, lymphocytes, and amoxicillin by means of phenotypic and
functional studies, including endocytosis, proliferation, and cytokine
production. RESULTS: Amoxicillin drove DCs from hypersensitive subjects to a
phenotypic and functional semimature status, inducing a T-cell proliferation
response. CONCLUSIONS: In delayed reactions to amoxicillin, DCs play a relevant
role in inducing the T-cell responses. These results are useful not only to
understand the mechanism but potentially as a possible approach to diagnosis.
CLINICAL IMPLICATIONS: A better understanding of T-cell and DC involvement in
delayed-type hypersensitivity reactions is needed. This in vitro assay might
provide clues to the diagnostic evaluation of patients allergic to penicillins.
PMID- 17030252
TI - Different eicosanoid profile of the hypersensitivity reactions triggered by
aspirin and celecoxib in a patient with sinusitis, asthma, and urticaria.
PMID- 17030253
TI - Swimming pool attendance and exhaled nitric oxide in children.
PMID- 17030254
TI - Correlation of FCERIB gene haplotypes with histamine release from basophils in
atopic asthma.
PMID- 17030255
TI - Opposing actions of (R,R)-isomers and (S,S)-isomers of formoterol on T-cell
function.
PMID- 17030256
TI - Symmetric, drug-related, intertriginous, and flexural exanthema in a patient with
polyvalent intolerance to corticosteroids.
PMID- 17030257
TI - Sensitization to Anisakis simplex: inhalant allergy versus gastroallergic
anisakiasis.
PMID- 17030259
TI - Eosinophilic bronchitis and asthma with sputum eosinophilia are different
entities.
PMID- 17030261
TI - The metal binding site of the major house dust mite allergen Der p 1.
PMID- 17030267
TI - Epidemiology of adenocarcinoma of the esophagogastric junction.
AB - The incidence of adenocarcinoma of the esophagogastric junction has increased
rapidly in the later half of the twentieth century in the United States and most
western countries. Although squamous cell carcinoma of the esophagus used to
predominate, adenocarcinoma of the distal esophagus and esophagogastric junction
now accounts for more than half of new diagnoses in western countries. There also
has been a shift from the development of distal gastric cancers to ones in a more
proximal location. These recent epidemiologic shifts have led to controversy
regarding the etiology and treatment of adenocarcinoma of the esophagogastric
junction. Uncertainty still exists with regards to nomenclature and
classification, risk factors, treatment, and screening and surveillance of
esophagogastric adenocarcinoma. This article examines the epidemiology and
etiologies of adenocarcinoma of the esophagogastric junction.
PMID- 17030268
TI - Pathologic risk factors of adenocarcinoma of the gastric cardia and
gastroesophageal junction.
AB - Available evidence supports the existence of two major pathways of neoplastic
development in the gastroesophageal region: the Barrett pathway, related to
gastroesophageal reflux disease, and the gastric pathway, related to Helicobacter
pylori infection. The existence of an independent junctional pathway is
questionable, and gastroesophageal junction adenocarcinomas share features of
esophageal and gastric adenocarcinomas. It has been impossible to accommodate all
data that are provided by different levels and tools of observation in tumors
that develop in the gastroesophageal region in a single, coherent classification.
That is why the stratification of pathologic risk in such tumors, and their
respective precursors, incorporates features from topography, histology,
immunohistochemistry, and molecular pathology.
PMID- 17030269
TI - Barrett's esophagus and adenocarcinoma of the gastroesophageal junction: a
pathologic perspective.
AB - Barrett's esophagus is defined clinically by the presence of endoscopically
evident columnar mucosa in the distal esophagus with histopathologic confirmation
of the presence of intestinal-type epithelium. The etiology of Barrett's
esophagus is understood poorly, but chronic gastroesophageal reflux disease is
considered a major contributing factor. Barrett's esophagus is associated with
the development of adenocarcinoma of the gastroesophageal junction. It is
believed that the development of a Barrett-type mucosa with intestinal goblet
type cells is due to an altered process of differentiation of pluripotent
epithelial stem cells in response to the local injury and repair process. The
potential identification and isolation of markers for screening purposes and
possibly prognostic information are areas of considerable clinical and scientific
interest.
PMID- 17030270
TI - Evolving role of (18)F-fluorodeoxyglucose positron emission tomography in the
management of esophageal carcinoma.
AB - Positron emission tomography (PTE) and PET/CT imaging with (18)F
fluorodeoxyglucose are metabolic imaging modalities that depict tissues based on
their level of glucose uptake. PET provides useful information in the primary
staging of disease. PET performance in detecting locoregional nodal metastases is
limited; however, it is the most accurate single noninvasive modality for
detecting distant metastases. It is the imaging modality of choice for whole-body
scanning in high-risk patients or patients who have clinically suspected
recurrence, and is particularly helpful in determining which patients are the
best candidates for surgical cure.
PMID- 17030271
TI - Adenocarcinoma of the esophagogastric junction: surgical therapy based on 1602
consecutive resected patients.
AB - Because of the borderline location between the esophagus and stomach, many
discrepancies exist in the current literature regarding the etiology,
classification, and surgical treatment of adenocarcinoma arising at the
esophagogastric junction. The classification of adenocarcinomas into three types,
AGE type I, type II, and type III, shows marked differences between the tumor
entities and is recommended for selection of a proper surgical approach. Complete
tumor resection and adequate lymphadenectomy are recommended for a good, long
term prognosis. With better surgical management and standardized procedures, even
the results in patients with more radical surgical approaches, the abdomino
thoracic esophagectomy improved.
PMID- 17030272
TI - Adenocarcinoma of the gastroesophageal junction: benefits of an extended
lymphadenectomy.
AB - The incidence of esophageal adenocarcinoma is rising faster the any other cancer
in the United States. Studies from around the world strongly suggest that for
early cancers of the lower esophagus and cardia, en bloc esophagogastrectomy
results in significantly better survival rates than does transhiatal
esophagogastrectomy.
PMID- 17030273
TI - Extent of surgical resection for esophageal and gastroesophageal junction
adenocarcinomas.
AB - The early-stage lymphatic dissemination in esophageal cancer poses challenges for
adequate surgical treatment. The role of extensive lymph node dissections remains
a matter of debate. Results of the only available large randomized controlled
trial suggest that fit patients who have esophageal cancer are treated best by a
transthoracic esophagectomy with extended en bloc (two-field) lymphadenectomy.
For less fit patients or patients who have junctional or cardiac tumors,
transhiatal esophageal resection could suffice. In patients who have truly
"early" adenocarcinoma (ie, with high-grade dysplasia or intramucosal carcinoma)
endoscopic resectional or ablative treatments may be suitable. When the tumor
invades the submucosal layer, the high risk for lymph node involvement and tumor
recurrence probably necessitates more extensive treatment schedules for
definitive cure.
PMID- 17030274
TI - Gastroesophageal carcinoma: individualized surgical therapy.
AB - During the twentieth century, surgical management of gastroesophageal carcinoma
was developed by an establishment of standard procedures with lymph node
dissection according to the metastatic distribution. The "fear" of invisible
micrometastasis caused surgeons to perform more aggressive resection with
lymphadenectomy to control the disease locally. Although several promising
results of extensive lymph node dissection have been reported, the prognostic
benefits of extensive surgery have not been proven by prospective randomized
trials. A novel technology to detect micrometastasis without extensive surgical
resection is required to gastroesophageal carcinoma. The lymphatic mapping
technique is one of the attractive candidates for a novel tool to approach this
issue.
PMID- 17030275
TI - Cancer of the gastroesophageal junction: combined modality therapy.
AB - Esophageal cancer, an uncommon, but highly virulent malignancy in the United
States, will be responsible for nearly 14,000 deaths in the year 2005. The
prognosis for patients who have adenocarcinoma of the distal esophagus and
gastroesophageal junction and who are treated with the standard approaches of
surgery or combined chemoradiation therapy is poor. Recent clinical trials have
evaluated the use of preoperative chemotherapy followed by surgery, combined
concurrent preoperative chemoradiotherapy followed by surgery, or definitive
chemoradiotherapy alone without surgery. This article focuses on recent advances
in the use of combined modality therapy in adenocarcinoma of the esophagus and
gastroesophageal junction.
PMID- 17030277
TI - Body art: piercing, tattooing, and scarification.
AB - Body art, particularly piercings and tattoos, is becoming more common. Many
patients get their first piercing or tattoo during adolescence or young
adulthood. Clinicians should understand the potential complications of these
procedures and their management. It also is important for clinicians to feel
comfortable counseling adolescents and their families about practices in safer
body art facilities.
PMID- 17030278
TI - Alternative and complementary therapies.
AB - The field of complementary and alternative medicine (CAM) is broad and diverse,
comprising numerous therapeutic modalities. CAM therapies are viewed as either an
adjunct or a complement to conventional treatment. As of 1997, 64% of United
States medical schools included elective or required CAM courses. The number of
CAM practitioners in the United States is projected to increase by 88% between
1994 and 2010, and the number of conventional physicians who incorporate CAM into
their practices will increase by 16%. Patients and their parents can make various
health care choices; doctors need to understand and respect these options, and to
support them, if safe and effective.
PMID- 17030279
TI - Immunization update: pertussis, meningoccocus, and human papillomavirus.
AB - New vaccines are being recommended for adolescents at a brisk pace. Immunization
is an effective preventive measure, and by bringing adolescents in for a medical
intervention, the new vaccines promise not only to protect adolescents from the
specific diseases they address, but also to enhance other health care services,
including screening for other health risk behaviors. This article discusses the
newest vaccination recommendations for adolescents pertaining to the
meningococcal and tetanus, diphtheria, and acellular pertussis vaccines and
reviews the human papillomavirus vaccines developed for use in the United States.
With the advent of these new vaccines, the potential exists to improve adolescent
health significantly through prevention, adding new incentive to increase
adolescent immunization rates for all indicated vaccines.
PMID- 17030280
TI - Supersize teens: the metabolic syndrome.
AB - With obesity and type 2 diabetes on the rise in children and adolescents, there
has been recent interest in the study of the metabolic (insulin resistance)
syndrome in this population. Characteristics of the syndrome include impaired
glucose tolerance, hypertension, dyslipidemia, and abdominal obesity. These
features are known to cluster and convey increased cardiovascular risk over time.
Screening of children and adolescents is important to the goal of prevention, and
therapeutic lifestyle modification is the primary treatment modality. When this
fails, pharmacotherapy aimed at the individual risk factors may be indicated.
PMID- 17030281
TI - Bariatric surgery in adolescents: an update.
AB - Bariatric surgery, although not a cure for obesity, can help selected extremely
obese adolescents achieve significant weight loss and improvement of obesity
related comorbidities, in conjunction with continued dietary and behavioral
interventions. This article summarizes the current guidelines for selection of
adolescent candidates for bariatric surgery and discusses the types of bariatric
procedures presently available for this age group. Data on the complications and
outcomes of bariatric surgery in this special population are reviewed.
PMID- 17030282
TI - Current concepts in acne management.
AB - Acne vulgaris is a nearly universal phenomenon among adolescents in the western
world and continues to remain problematic for a significant proportion of adults.
During adolescence, emotional and physical changes must be successfully
integrated into the emerging sense of self, and skin disorders such as acne,
which alter that self-image, may engender distressing feelings of embarrassment,
shame, and disgust. While most patients eventually achieve spontaneous remission,
approximately one quarter of teenagers will show evidence of permanent acne
scarring by 18 years of age. This article reviews current information regarding
the pathophysiology, clinical manifestations, differential diagnosis, and therapy
of the adolescent patient who has acne, and emphasizes recent advances in acne
management.
PMID- 17030283
TI - Bone health in adolescents.
AB - Adolescence is a crucial period for the accrual of bone density and achievement
of peak bone mass. Unique situations can arise during adolescence that place an
adolescent at risk for bone loss or the failure to attain appropriate bone mass.
Clinicians also are challenged by the limitations of currently available
measurement tools to evaluate skeletal status in young patients. This article
reviews medical approaches to prevent bone loss in patients with eating disorders
and the skeletal effects of specific hormonal contraceptive agents. Adolescent
medicine specialists and gynecologists caring for teenagers must recognize the
potential implications of these clinical settings on bone health to provide
appropriate patient guidance and direct management.
PMID- 17030284
TI - Advances in hormonal contraception.
AB - This article presents a review of advances made in hormonal contraception over
the past 15 years. It looks at the different routes of administration that have
been developed, at newer formulations of conventional methods, and at novel
contraceptive agents that are in the process of approval. The article provides a
short description of each of these contraceptive methods, information about
compliance, side effects, and efficacy, and an update on that particular method.
PMID- 17030285
TI - Vaginal microbicides.
AB - This article reviews the current status of microbicide development and challenges
faced in developing safe and effective compounds. The ever growing HIV pandemic,
lack of effective vaccines against HIV and other sexually transmitted infections,
concern about the vulnerability of women, and difficulty in condom negotiation
are factors that drive the development of topical microbicides as a prophylactic
method for women. The ideal microbicide needs to be safe and highly effective and
not increase viral resistance or cause disruption of host defenses. Advances in
the understanding of HIV transmission and the role of other sexually transmitted
infections have allowed progress in development of microbicide candidates as
clinical trials of potential agents are awaited.
PMID- 17030286
TI - Expedited partner therapy for adolescents diagnosed with gonorrhea or chlamydia:
a review and commentary.
AB - Management of sex partners is a cornerstone of sexually transmitted infection
control in the United States. Face-to-face investigation and notification of
exposure of sex partners by public health professionals seems to be the most
effective method of ensuring appropriate partner management. However, resources
rarely permit such intensive partner management for gonorrhea and chlamydial
infection. Alternatives to public health-assisted notification and referral
include expedited partner therapy, in which partners are treated before
evaluation, most typically through patient-delivered therapy. Results from trials
have shown generally favorable biomedical and behavioral outcomes. This article
discusses the evidence for expedited partner therapy and its associated
liability, confidentiality, financial, and administrative issues relating to
adolescent patients and their health care providers.
PMID- 17030287
TI - Tobacco use cessation for adolescents.
AB - Adolescent tobacco users are unique. Thus far, effective interventions for adult
tobacco users have been disappointing when applied to adolescents. This article
reviews current evidence regarding adolescent tobacco use cessation
interventions, explores under-researched areas in tobacco use cessation for
adolescents, and offers assistance with treating adolescent tobacco users across
the spectrum of use. A means of assessment and treatment of the adolescent smoker
is proposed, and cases are included to assist the practitioner with treatment of
the experimental tobacco user, the "adolescent-type" intermittent user, and the
daily "adult-type" of adolescent tobacco user.
PMID- 17030288
TI - Performance-enhancing drug use in young athletes.
AB - This article explores the issue of performance-enhancing drug use in adolescent
athletes. The article describes current substances that are being used by
adolescent athletes, explains their positive and negative effects, examines
factors contributing to their increased use in adolescent athletes, and discusses
approaches to educating adolescents about alternate means of enhancing their
athletic performance. It is hoped that this information will be useful toward
encouraging young athletes to pursue, safe, healthy, and natural means of
performance enhancement, such as practice and strength training, to improve
sports performance in a safe, effective manner.
PMID- 17030289
TI - Abuse of proprietary (over-the-counter) drugs.
AB - A predominantly overlooked type of substance abuse by adolescents and young
adults in the United States and around the world is the abuse of medications and
other products sold without a prescription, or over-the-counter (OTC), to the
public. OTC substance abuse causes significant morbidity and mortality, and there
are concerns that some types of OTC substance abuse are increasing. Regular
office screening for inhalant abuse and other substance abuse and health risk
behaviors must be part of standard pediatric care. This article discusses what is
known about the extent and clinical impact of OTC substance abuse and reviews key
points about recognition, detection, and management.
PMID- 17030291
TI - Asperger's syndrome.
AB - Asperger's syndrome is a pervasive developmental disorder characterized by social
impairments and rigid and repetitive interests or behaviors paired with
relatively preserved cognitive and verbal facilities. This article describes the
clinical manifestation of the disorder and guidelines for diagnostic assessment
and intervention. Existing research is reviewed within the areas of epidemiology,
medical/neurobiologic factors, genetics, and outcome, and future directions for
research are recommended.
PMID- 17030290
TI - Prescription drug misuse: a growing national problem.
AB - Misuse of prescription drugs has been a growing problem in the United States
affecting all age groups, including adolescents. Recent years have produced many
advances in medical management of chronic pain, depression and anxiety, and
attention-deficit/hyperactivity disorder. Many of the medications used to treat
these disorders, such as the opioids, benzodiazepines, and psychostimulants, also
have potential for abuse and dependence. The challenge for the clinician today is
to maximize safe and effective treatment with available medication, while
preventing the diversion of prescribed medication or the development of substance
related disorders in patients receiving these medications.
PMID- 17030293
TI - Enriching clinical knowledge.
PMID- 17030292
TI - Adolescent psychopharmacology: drugs for mood disorders.
AB - This article reviews mood disorders in children and adolescents, the diagnostic
criteria, and important differential diagnoses to be considered. Critical points
in the treatment of mood disorders and comorbid conditions and the important role
the primary care provider can play in their management are stressed. Warning
signs to identify adolescents who may be at risk of attempting suicide are
discussed.
PMID- 17030294
TI - Potential drug-herb interaction with antiplatelet/anticoagulant drugs.
AB - This is a cross-sectional survey evaluating the use of herbal medicines in
medical wards patients that may interfere with the effect of antiplatelet or
anticoagulant therapy. Among the 250 patients participated, 42.4% (n=106) were
taking herbs with 76 patients (71.7%) using herbs for the past 12 months.
Overall, almost 31% (n=23, N=76) of patients were taking one or more of the
specified herbal medicines [ginseng (Panax ginseng), garlic (Allium sativum),
ginkgo (Gingko biloba) thought to interact with antiplatelet or anticoagulant
therapy. The study showed that 21% (n=16, N=76) of patients co-ingested specified
herbs with antiplatelet or anticoagulant therapy, of which half of them were at
risk of potential drug-herb interactions. A large proportion of respondents
involved in potential drug-herb interaction were elderly people (62.5%, n=5).
However, more than 90% of herbal users did not disclose the use of herbal
medicine to their health professionals. It is thus prudent for all care givers to
be aware of the possibility of drug-herb interaction and inquire about herbal use
from patients.
PMID- 17030295
TI - Complementary and alternative medicine use in British Columbia--a survey of HIV
positive people on antiretroviral therapy.
AB - In 2002, the British Columbia (BC) Centre for Excellence in HIV/AIDS collected
final detailed data on complementary and alternative medicine (CAM) use in their
HIV treatment program. This cross-sectional study of 682 participants examines
types and determinants of CAM use in this program, and examines adverse effects
associated with CAM use and antiretroviral therapy (ART). Among the 47% ever CAM
users in the included population, vitamins/minerals (81%), meditation/yoga (36%),
massage (31%), marijuana (30%), dietary supplements (24%), and herbal medicines
(19%), were most commonly used. Multivariate analysis indicated CAM users were
less likely to have low education (AOR=0.51), more likely to be unemployed
(AOR=1.52), more likely to have been on ART longer (AOR=1.19), and more likely to
experience objective, action-requiring (OA) side effects (AOR=1.45). CAM use is
common. Both patients and health professionals should be aware of potential
toxicities and drug interactions related to the use of CAM and HIV/AIDS
treatment.
PMID- 17030296
TI - Auditing outcomes and costs of integrated complementary medicine provision--the
importance of length of follow up.
AB - A retrospective audit was carried out on 58 patients with chronic health problems
who were referred by 22 general practitioners (GPs) for acupuncture,
aromatherapy, homeopathy, massage and osteopathy, or a combination. Costs of GP
consultations, prescriptions, secondary care referrals, and diagnostic tests from
records of 33 of these patients were compared pre (24 months), during (mean 4.3
months) and post (mean 5.7 months) complementary medicine (CM) treatment. Patient
centred outcome data included the Measure Yourself Medical Outcome Profile
(MYMOP) and content analysis of patient and practitioner comments. Costs of GP
consultations/patient/month were significantly higher during (20.10 pounds,
p<0.001) and post (17.53 pounds, p<0.01) CM treatment compared with pre-treatment
costs (11.27 pounds). Total prescription costs were not significantly higher
during and post-treatment than pre-treatment. Prescription costs for referred
conditions were lower during (2.26 pounds) and higher post-treatment (3.75
pounds) compared with costs pre-treatment (3.24 pounds). Pre- and post-treatment
MYMOP scores indicated significant improvements in health and well-being. Longer
follow up, is required in order to demonstrate significant cost savings related
to CM provision. Cost comparisons with conventional medicine should consider
quantitative and qualitative data to capture the wider benefits experienced by
patients.
PMID- 17030297
TI - Models of health: a survey of practitioners.
AB - PURPOSE: Models of health influence providers' practice and delivery of health
care. This study surveyed a random sample of providers to determine if health
care providers from mainstream medicine (MM), integrative medicine (IM), and
complementary and alternative medicine (CAM) hold mutually exclusive models of
health or combine notions from models thought to be contradictory. METHODS: A
survey was created through qualitative research, piloted, and mailed to a wide
variety of MM, IM, and CAM health care professionals. RESULTS: All providers
combined various models and definitions of health. Most utilized the biomedical
approach to some extent. Balance (holistic model) and functioning in daily life
were essential to most respondents' models of health, disease, and healing. Close
communication between MM and CAM systems was preferred over complete separation
or a single system. CONCLUSIONS: Many providers of all types combine widely
disparate components in their definitions of health, providing keys for improving
communication.
PMID- 17030298
TI - The upside of cancer--a personal account of embracing life with cancer.
AB - Carol Edmonston was first diagnosed with breast cancer in 1995. After a
lumpectomy and 6 weeks of daily radiation therapy she continued living a full
life. Exactly 2 years later she was diagnosed with an unrelated cancer in her
other breast following a routine mammogram. She had a lumpectomy, along with
lymph node dissection, followed by 6 weeks of daily radiation therapy. Upon
completion, she took Tamoxifen for 5 years and is currently cancer free, enjoying
a full and rich life. The following story offers a unique insight into one
person's spiritual adventure through cancer and the personal transformation that
followed using "Doodling" as a therapeutic tool.
PMID- 17030299
TI - Prevalence surveys: to be taken with a pinch of salt.
PMID- 17030300
TI - Kampo medicines as alternatives for treatment of migraine: six case studies.
AB - Kampo is a well-recognized form of traditional medicine in Japan. This paper
reports upon six cases of successful use of Kampo medicines, herbal medicine
preparations, for the treatment of migraine. Most of the patients had been
treated with conventional medicines, such as non-steroidal anti-inflammatory
drugs or triptans, but were not satisfied with the outcomes of these conventional
treatments with regard to their effectiveness or feelings of discomfort after
administration. We administered two Kampo medicines, goshuyuto for prevention of
migraine and senkyuchachosan as a painkiller. Both Kampo medicines worked
successfully in the treatment of migraine and the patients were satisfied with
their effects. Kampo medicine seems a favorable candidate for alternative therapy
of migraine.
PMID- 17030301
TI - Paving the way for complementary medicine?
PMID- 17030302
TI - Implicit solvent models.
AB - Implicit solvent models for biomolecular simulations are reviewed and their
underlying statistical mechanical basis is discussed. The fundamental quantity
that implicit models seek to approximate is the solute potential of mean force,
which determines the statistical weight of solute conformations, and which is
obtained by averaging over the solvent degrees of freedom. It is possible to
express the total free energy as the reversible work performed in two successive
steps. First, the solute is inserted in the solvent with zero atomic partial
charges; second, the atomic partial charges of the solute are switched from zero
to their full values. Consequently, the total solvation free energy corresponds
to a sum of non-polar and electrostatic contributions. These two contributions
are often approximated by simple geometrical models (such as solvent exposed area
models) and by macroscopic continuum electrostatics, respectively. One powerful
route is to approximate the average solvent density distribution around the
solute, i.e. the solute-solvent density correlation functions, as in statistical
mechanical integral equations. Recent progress with semi-analytical
approximations makes continuum electrostatics treatments very efficient. Still
more efficient are fully empirical, knowledge-based models, whose relation to
explicit solvent treatments is not fully resolved, however. Continuum models that
treat both solute and solvent as dielectric continua are also discussed, and the
relation between the solute fluctuations and its macroscopic dielectric
constant(s) clarified.
PMID- 17030303
TI - Temperature dependence of the solubility of non-polar gases in water.
AB - An explanation is provided for the experimentally observed temperature dependence
of the solubility and the solubility minimum of non-polar gases in water. The
influence of solute size and solute-water attractive interactions on the
solubility minimum temperature is investigated. The transfer of a non-polar
solute from the ideal gas into water is divided into two steps: formation of a
cavity in water with the size and shape of the solute and insertion of the solute
in this cavity which is equivalent to 'turning on' solute-water attractive
interactions. This two step process divides the excess chemical potential of the
non-polar solute in water into repulsive and attractive contributions,
respectively. The reversible work for cavity formation is modeled using an
information theory model of hydrophobic hydration. Attractive contributions are
calculated by modeling the water structure in the vicinity of non-polar solutes.
These models make a direct connection between microscopic quantities and
macroscopic observables. Moreover, they provide an understanding of the peculiar
temperature dependences of the hydration thermodynamics from properties of pure
water; specifically, bulk water density and the water oxygen-oxygen radial
distribution function.
PMID- 17030304
TI - Towards a better description and understanding of biomolecular solvation.
AB - We introduce a flexible framework for the correct description of the solvation of
biological macromolecules, the dielectric field equation (DFE). The formalism
permits the use of any combination of quantum mechanical (QM), molecular
mechanical (MM) and continuum electrostatic (CE) based techniques. For the CE
region a method that yields the electric field rather than the potential is
outlined. The DFE formalism makes clear the need to consider and to calibrate a
dielectric boundary region surrounding the simulation system. The details of how
to do this are presented for the case of the Ewald summation method; the effects
are demonstrated by calculations of the dielectric properties and the spatially
resolved Kirkwood G-factor, G(K)(r), of TIP3P water. Computing the dielectric
properties of a multi-component system provides a sensitive method to better
understand the solvation of biological macromolecules. Towards this goal a
rigorous analysis of the dielectric properties of solvated biomolecules based on
a decomposition of the frequency-dependent dielectric constant (or
susceptibility) of the full system is presented. The meaning of our approach is
investigated, and the results of a first application are reported. Using the
method of Voronoi polyhedra, the dielectric properties of the first two solvation
shells and bulk water are compared by re-analyzing a 12-ns trajectory of a zinc
finger peptide in water [Loffler et al. J. Mol. Biol. 270 (1997) 520]. It is
found that the first shell behaves considerably different; in addition, there is
a non-negligible contribution to the total susceptibility of the system from
coupling between the protein and the bulk water phase, i.e. the water molecules
not in the immediate vicinity of the solute.
PMID- 17030305
TI - Optimized atomic radii for protein continuum electrostatics solvation forces.
AB - Recently, we presented a Green's function approach for the calculation of
analytic continuum electrostatic solvation forces based on numerical solutions of
the finite-difference Poisson-Botzmann (FDPB) equation [Im et al., Comp. Phys.
Comm. 111 (1998) 59]. In this treatment the analytic forces were explicitly
defined as the first derivative of the FDPB continuum electrostatic free energy
with respect to the coordinates of the solute atoms. A smooth intermediate region
for the solute-solvent dielectric boundary needed to be introduced to avoid
abrupt discontinuous variations in the solvation free energy and forces as a
function of the atomic positions. In the present paper we extend the set of
optimized radii, which was previously parametrized from molecular dynamics free
energy simulations of the 20 standard amino acids with explicit solvent molecules
[Nina et al., J. Phys. Chem. 101 (1997) 5239], to yield accurate solvation free
energy by taking the influence of the smoothed dielectric region into account.
PMID- 17030306
TI - Integral equation theories for predicting water structure around molecules.
AB - Water plays a crucial role in the structure and function of proteins and other
biological macromolecules; thus, theories of aqueous solvation for these
molecules are of great importance. However, water is a complex solvent whose
properties are still not completely understood. Statistical mechanical integral
equation theories predict the density distribution of water molecules around a
solute so that all particles are fully represented and thus potentially both
molecular and macroscopic properties are included. Here we discuss how several
theoretical tools we have developed have been integrated into an integral
equation theory designed for globular macromolecular solutes such as proteins.
Our approach predicts the three-dimensional spatial and orientational
distribution of water molecules around a solute. Beginning with a three
dimensional Ornstein-Zernike equation, a separation is made between a reference
part dependent only on the spatial distribution of solvent and a perturbation
part dependent also on the orientational distribution of solvent. The spatial
part is treated at a molecular level by a modified hypernetted chain closure
whereas the orientational part is treated as a Boltzmann prefactor using a quasi
continuum theory we developed for solvation of simple ions. A potential energy
function for water molecules is also needed and the sticky dipole models of
water, such as our recently developed soft-sticky dipole (SSD) model, are ideal
for the proposed separation. Moreover, SSD water is as good as or better than
three point models typically used for simulations of biological macromolecules in
structural, dielectric and dynamics properties and yet is seven times faster in
Monte Carlo and four times faster in molecular dynamics simulations. Since our
integral equation theory accurately predicts results from Monte Carlo simulations
for solvation of a variety of test cases from a single water or ion to ice-like
clusters and ion pairs, the application of this theory to biological
macromolecules is promising.
PMID- 17030307
TI - Description of hydration free energy density as a function of molecular physical
properties.
AB - A method to calculate the solvation free energy density (SFED) at any point in
the cavity surface or solvent volume surrounding a solute is proposed. In the
special case in which the solvent is water, the SFED is referred to as the
hydration free energy density (HFED). The HFED is described as a function of some
physical properties of the molecules. These properties are represented by simple
basis functions. The hydration free energy of a solute was obtained by
integrating the HFED over the solvent volume surrounding the solute, using a grid
model. Of 34 basis functions that were introduced to describe the HFED, only six
contribute significantly to the HFED. These functions are representations of the
surface area and volume of the solute, of the polarization and dispersion of the
solute, and of two types of electrostatic interactions between the solute and its
environment. The HFED is described as a linear combination of these basis
functions, evaluated by summing the interaction energy between each atom of the
solute with a grid point in the solvent, where each grid point is a
representation of a finite volume of the solvent. The linear combination
coefficients were determined by minimizing the error between the calculated and
experimental hydration free energies of 81 neutral organic molecules that have a
variety of functional groups. The calculated hydration free energies agree well
with the experimental results. The hydration free energy of any other solute
molecule can then be calculated by summing the product of the linear combination
coefficients and the basis functions for the solute.
PMID- 17030308
TI - Application of a universal solvation model to nucleic acid bases: comparison of
semiempirical molecular orbital theory, ab initio Hartree-Fock theory, and
density functional theory.
AB - The free energies of solvation of six nucleic acid bases (adenine, cytosine,
hypoxanthine, guanine, thymine, and uracil) in water and chloroform are
calculated using CM2 class IV charges and SM5.42R atomic surface tensions. Using
any of three approximations to the electronic wave function (AM1, Hartree-Fock,
or DFT), we obtain good agreement with experiment for five cases where the
experimental results are known for the partition coefficients between the two
solvents. Decomposition of the solvation effects into bulk electrostatic
contributions and first-solvation-shell effects shows that the partitioning is
dominated by the former, and this illustrates the importance of using accurate
partial atomic charges for modeling these molecules in aqueous solution.
PMID- 17030309
TI - Heat capacity and compactness of denatured proteins.
AB - One of the striking results of protein thermodynamics is that the heat capacity
change upon denaturation is large and positive. This change is generally ascribed
to the exposure of non-polar groups to water on denaturation, in analogy to the
large heat capacity change for the transfer of small non-polar molecules from
hydrocarbons to water. Calculations of the heat capacity based on the exposed
surface area of the completely unfolded denatured state give good agreement with
experimental data. This result is difficult to reconcile with evidence that the
heat denatured state in the absence of denaturants is reasonably compact. In this
work, sample conformations for the denatured state of truncated CI2 are obtained
by use of an effective energy function for proteins in solution. The energy
function gives denatured conformations that are compact with radii of gyration
that are slightly larger than that of the native state. The model is used to
estimate the heat capacity, as well as that of the native state, at 300 and 350 K
via finite enthalpy differences. The calculations show that the heat capacity of
denaturation can have large positive contributions from non-covalent intraprotein
interactions because these interactions change more with temperature in non
native conformations than in the native state. Including this contribution, which
has been neglected in empirical surface area models, leads to heat capacities of
unfolding for compact denatured states that are consistent with the experimental
heat capacity data. Estimates of the stability curve of CI2 made with the
effective energy function support the present model.
PMID- 17030310
TI - Calculation of short-range interactions between proteins.
AB - Macromolecular association is an integral component of numerous cellular and
technologically relevant processes. Most molecular theories of such association
neglect the explicit solvent structure and rely on continuum concepts such as
surface energies for calculating short-range interactions. We present a new such
method for calculating the non-electrostatic component of the interaction-free
energy, based on formalisms for calculating dispersion interactions between
macromolecules. The interactions are separated into a short-ranged component that
is treated atomistically, and a longer range component that is treated within the
continuum Lifshitz-Hamaker approach. This description avoids the singularities
inherent in the continuum dispersion formulation, and its effectiveness in
characterizing the shape complementarity between interacting surfaces is shown to
be comparable to that of surface area-based methods of similar parametric
complexity. An advantage of the new method is that it allows facile calculation
of the interaction free energy as a function of intermolecular separation,
including steric effects; this makes it suitable for use in simulations of
protein solutions.
PMID- 17030311
TI - Electronic structure and biological activity of steroids.
AB - We present the analysis of the electronic structure for 31 steroids by using HeI
UV photoelectron spectroscopy (UPS) and MO calculations. The electronic structure
of molecules in the gas phase is related directly to steroid-receptor binding
measurements. The results indicate that formally 'inert' sigma-skeleton plays a
crucial role in diversifying the electronic structures of the title compounds
('ribbon-orbital effect'). This is an attempt to rationalize the biological
activity of steroids (represented through steroid-receptor binding) by making
direct correlation between spectroscopic and biological data.
PMID- 17030312
TI - Long-term molecular dynamics simulation of copper azurin: structure, dynamics and
functionality.
AB - A long-term molecular dynamics simulation (1.1 ns), at 300 K, of fully hydrated
azurin has been performed to put into relationship the protein dynamics to
functional properties with particular attention to those structural elements
involved in the electron transfer process. A detailed analysis of the root mean
square deviations and fluctuations and of the intraprotein H-bonding pattern has
allowed us to demonstrate that a rigid arrangement of the beta-stranded protein
skeleton is maintained during the simulation run, while a large mobility is
registered in the solvent-exposed connecting regions (turns) and in the alpha
helix. Moreover, the structural elements, likely involved in the electron
transfer path, show a stable H-bonding arrangement and low fluctuations. Analysis
of the dynamical cross-correlation map has revealed the existence of correlated
motions among residues connected by hydrogen bonds and of correlated and anti
correlated motions between regions which are supposed to be involved in the
functional process, namely the hydrophobic patch and the regions close to the
copper reaction center. The results are briefly discussed also in connection to
the current through-bond tunneling model for the electron transfer process.
Finally, a comparison with the structural and the dynamical behaviour of
plastocyanin, whose structure and functional role are very similar to those of
azurin, has been performed.
PMID- 17030313
TI - Paramagnetic fluorescence quenching in a model membrane: a consideration of
lifetime and temperature.
AB - To expand our understanding of paramagnetic quenching in membranes, the
relationship between fluorophore excited-state lifetime (tau), temperature, and
the collisional quenching was studied. Specifically, the ability of tempo to
quench the steady-state and time-resolved emission from five lipophilic
fluorophores (diphenylhexatriene, perylene, phenanthrene, pyrene, and
triphenylene) partitioned into egg phosphatidylcholine (EggPC) liposomes was
examined. Also, the temperature dependence of spin-labeled androstane to quench
the emission (steady-state and time-resolved) from perylene in EggPC liposomes
was determined. Unexpectedly, in EggPC liposomes, the apparent quenching
efficiency decreased with increasing tau until the effect leveled off above
approximately 20 ns. Moreover, in EggPC liposomes, dynamic quenching decreased
with increasing temperature. The results suggest that in membranes, paramagnetic
quenching is more complex than generally recognized.
PMID- 17030314
TI - Electrospray ionization mass spectrometry in the study of biomolecular non
covalent interactions.
AB - In the past mass spectrometry has been limited to the study of small, stable
molecules, however, with the emergence of electrospray ionization mass
spectrometry (ESI-MS) large biomolecules as well as non-covalent biomolecular
complexes can be studied. ESI-MS has been used to study non-covalent interactions
involving proteins with metals, ligands, peptides, oligonucleotides, as well as
other proteins. Although complementary to other well-established techniques such
as circular dichroism and fluorescence spectroscopy, ESI-MS offers some
advantages in speed, sensitivity, and directness particularly in the
determination of the stoichiometry of the complex. One major advantage is the
ability of ESI-MS to provide multiple signals each arising from a distinct
population within the sample. In this review I will discuss some of the different
types of non-covalent biomolecular interactions that have been studied using ESI
MS, highlighting examples which show the efficacy of using ESI-MS to probe the
structure of biomolecular complexes.
PMID- 17030315
TI - Structural and thermodynamic studies of KM+, a d-mannose binding lectin from
Artocarpus integrifolia seeds.
AB - The KM+ lectin exhibits a novel and unusual circular dichroism (CD) spectrum that
could be explained by a high proline content that would be inducing deformation
of the beta-structure and/or unusual turns. KM+ was shown to be a very rigid
lectin, which was very stable under a broad variety of conditions (urea,
guanidine, hydrolysis, pH, etc.). Only incubation for 60 min at 333-338 K and
extreme basic pH were able to induce conformational changes which could be
observed by CD and fluorescence measurements. Data from CD are typical for
protein denaturing associated with changes in the overall secondary structure.
Data from high-performance size exclusion chromatography (SEC) showed that the
denatured forms produced at pH 12.0 are eluted in clusters that co-elute with the
native forms. A significant contribution from the tyrosines to the fluorescence
emission upon denaturation was observed above 328 K. In fact at 328 K some
broadening of the emission spectrum takes place followed by the appearance of a
shoulder (approx. 305 nm) at 333 K and above. The sensitivity of tryptophan
fluorescence to the addition of sugar suggests a close proximity of the
tryptophan residues to the sugar binding site, K(a)=(2.9+/-0.6)x10(3) M(-1). The
fraction of chromophore accessible to the quencher obtained is f(a)=0.43+/-0.08,
suggesting that approximately 50% of the tryptophan residues are not accessible
to quenching by d-mannose. KM+ thermal denaturation was found to be irreversible
and was analyzed using a two-state model (N-->D). The results obtained for the
activation energy and transition temperature from the equilibrium CD studies
were: activation energy, E(a)=134+/-11 kJ/mol and transition temperature,
T(m)=339+/-1 K, and from the fluorescence data: E(a)=179+/-18 kJ/mol and
T(m)=337+/-1 K. Kinetic studies gave the following values: E(a)=108+/-18 kJ/mol
and E(a)=167+/-12 kJ/mol for CD and fluorescence data, respectively.
PMID- 17030316
TI - Energetics of Ca(2+)-EDTA interactions: calorimetric study.
AB - The interaction between Ca(2+) and EDTA has been studied using isothermal
titration calorimetry to elucidate the detailed mechanism of complex formation
and to relate the apparent thermodynamic parameters of calcium binding to the
intrinsic effects of ionization. It has been shown that Ca(2+) binding to EDTA is
an exothermic process in the temperature range 5-48 degrees C and is highly
dependent on the buffer in which the reaction occurs. Calorimetric measurements
along with pH-titration of EDTA under different solvent conditions shows that the
apparent enthalpy effect of the binding is predominantly from the protonation of
buffer. Subtraction of the ionization effect of buffer from the total enthalpy
shows that the enthalpy of binding Ca(2+) to EDTA is -0.56 kcal mol(-1) at pH
7.5. The DeltaH value strongly depends on solvent conditions as a result of the
degree of ionization of the two amino groups in the EDTA molecule, but depends
little on temperature, indicating that the heat capacity increment for metal
binding is close to zero. At physiological pH values where the amino groups of
EDTA with pK(a)=6.16 and pK(a)=10.26 are differently ionized, the coordination of
the Ca(2+) ion into the complex leads to release of one proton due to
deprotonation of the amino group having pK(a)=10.26. Increasing the pH up to
11.2, where little or no ionization occurs, leads to elimination of the enthalpy
component due to ionization, while its decrease to pH 2 leads to its increase,
due to protonation of the two amino groups. The heat effect of Ca(2+)/EDTA
interactions, excluding the deprotonation enthalpy of the amino groups, i.e. that
associated with the intrinsic enthalpy of binding, is higher in value
(Delta(b)H(o)=-5.4 kcal mol(-1)) than the apparent enthalpy of binding. Thus, the
large DeltaG value for Ca(2+) binding to EDTA arises not only from favorable
entropic but also enthalpic changes, depending on the ionization state of the
amino groups involved in coordination of the calcium. This explains the great
variability in DeltaH obtained in previous studies. The ionization enthalpy is
always unfavorable, and therefore dramatically decreases Ca(2+) affinity by
reduction of the enthalpy term of the stability function. The origin of the
enthalpy and entropy terms in the stability of the Ca(2+)-EDTA complex is
discussed.
PMID- 17030317
TI - Complex patterns predicted in an in vitro experimental model system for the
evolution of molecular cooperation.
AB - An isothermal biochemical in vitro amplification system with two trans
cooperatively coupled amplifying DNA molecules was investigated homogeneously
using a hierarchy of kinetic models and as a simplified reaction-diffusion
system. In our model of this recently developed experimental system, no reaction
mechanism higher than second order occurs, yet numerical simulations show a
variety of complex spatiotemporal patterns which arise in response to finite
amplitude perturbations in a flow reactor. In a certain domain of the kinetic
parameters the system shows self-replicating spots. These spots can stabilize the
cooperative amplification in such evolving systems against emerging parasites.
The results are of high relevance for experimental studies on these functional in
vitro ecosystems in spatially resolved microstructured reactors.
PMID- 17030318
TI - Effect of Na(+) concentration on the subgel phases of negatively charged
phosphatidylglycerol.
AB - The effect of Na(+) concentration on the subgel phase of
dimyristoylphosphatidylglycerol (DMPG) was investigated by differential scanning
calorimetry (DSC) and negative stain electron microscopy, and the results were
compared with dipalmitoylphosphatidylglycerol (DPPG). The conversion mode of DMPG
vesicle to the subgel phase by annealing at 5 degrees C was grouped into two
types depending on whether Na(+) concentration is above or below 200-250 mM. For
[Na(+)]>200-250 mM, the subgel phase of a crystalline superstructure of bilayers
wrapped in a cylinder was attained during a 24-h period of annealing and
transformed directly to the liquid crystal phase on heating. For [Na(+)]<200-250
mM, two subgel phases which transform to the gel phase on heating were observed
after annealing up to 24 h. Both subgel phases showed belt-like structures
composed of loosely and closely stacked lamellae, respectively, and their
fractions were found to depend on Na(+) concentration. With a further annealing
up to 30 days, only the closely stacked subgel phase converted subsequently into
the cylindrical superstructure of a more ordered phase. Similar two subgel phases
were detected for DPPG at [Na(+)]< or =100 mM. The difference in the relative
enthalpy between the gel and subgel phases was investigated from the van der
Waals interaction energy between the hydrocarbon chains.
PMID- 17030319
TI - A fluorescence study of the molecular interactions of harmane with the
nucleobases, their nucleosides and mononucleotides.
AB - Fluorescence binding studies of harmane to the elemental components of the
nucleic acids were undertaken to investigate the origin of the interaction
between the drug and DNA. Most of the tested substrates have been found to induce
hypochromism in the absorption spectrum of harmane and to quench its
fluorescence. The quenching process induced by the nucleobases and their
nucleosides is mainly due to the formation of ground state 1:1 complexes.
However, in the case of the mononucleotides a dynamic quenching component is also
observed. This quenching component is likely due to the excited state interaction
of harmane with the phosphate group of the nucleotides. UV-vis spectral changes
and quenching measurements have been used to quantify the ground state
association constants of the complexes and the quenching rate constants.
PMID- 17030320
TI - Free radical scavenging ability and antioxidant efficiency of curcumin and its
substituted analogue.
AB - Free radical reactions of curcumin and its ethoxy substituted derivative (C1) 1,7
bis-(4-hydroxy-3-ethoxy phenyl)-1,6-heptadiene-3,5-dione have been studied using
a pulse radiolysis technique in homogeneous aqueous-organic solutions like
acetonitrile-water and isopropanol-water mixtures, as well as in neutral TX-100
and cationic CTAB micellar solutions. The phenoxyl radicals of curcumin or C1
were generated by one-electron transfer to several oxidants like N(3)(.), Br(2)(
.), CCl(3)O(2)(.), glutathione radicals which exhibit absorption from a 300-600
nm wavelength region with the maximum at 490-500 nm. Other important properties
of the phenoxyl radicals such as extinction coefficient, radical lifetime and
their formation and decay rate constants were also determined in these systems.
The antioxidant property of curcumin and C1 were estimated in terms of their
ability to inhibit the lipid peroxidation in liposomes and also in terms of
trolox equivalent antioxidant capacity (TEAC). The results were compared with
alpha-tocopherol.
PMID- 17030321
TI - Inverted hexagonal and cubic phases induced by alpha-tocopherol in fully hydrated
dispersions of dilauroylphosphatidylethanolamine.
AB - The effect of alpha-tocopherol on the thermotropic phase behaviour and structure
of aqueous dispersions of 1,2-di-lauryl-sn-glycero-3-phosphoethanolamine was
examined by synchrotron X-ray diffraction. The pure phospholipid exhibited a
lamellar gel to liquid-crystal phase transition at 30 degrees C on heating at 3
degrees C min(-1) between 10 degrees C and 90 degrees C. The transition was
reversible with a temperature hysteresis of 0.3 degrees C on cooling. At
temperatures less than 10 degrees C only lamellar gel phase of the pure
phospholipid was seen in co-dispersions of up to 20 mol % alpha-tocopherol. The
presence of 2.5 mol % alpha-tocopherol caused the appearance of inverted
hexagonal phase at temperatures just below the main phase transition temperature
that co-existed with the lamellar gel phase. The intensity of scattering from the
hexagonal-II phase increased with increasing proportion of alpha-tocopherol in
the mixture and in proportions greater than 10 mol % it persisted at temperatures
above the main transition and co-existed with the lamellar liquid-crystal phase
of the pure phospholipid. At higher temperatures all co-dispersions containing up
to 15 mol % alpha-tocopherol showed the presence of cubic phases. These phases
indexed a Pn3m or Pn3 space grouping. When the proportion of alpha-tocopherol was
increased to 20 mol % the only non-lamellar phase observed was inverted hexagonal
phase. This phase co-existed with lamellar gel and liquid-crystal phases of the
pure phospholipid, but was the only phase present at temperatures >60 degrees C.
The X-ray diffraction data were used to construct a partial phase diagram of the
lipid mixture in excess water between 10 degrees and 90 degrees C and up to 20
mol % alpha-tocopherol in phospholipid.
PMID- 17030322
TI - A statistical mechanical theory for the adsorption of protein to liposomal
membranes.
AB - The observed topology change of spherical lipid vesicles to coffee cups [Saitoh,
A. et al., Proc. Natl. Acad. Sci. USA 95 (1998) 1026] was analyzed by a
statistical mechanical theory. The topology change was due to the adsorption of
talin molecules to the orifices of the coffee cups. The adsorption isotherm of
talin between an aqueous solution and the vesicle membrane was analyzed by taking
account of the bending energy of the membrane. The equilibrium is determined by
the balance of the energy gain for the adsorption of talin to the periphery of
the vesicles and the change of the bending energy of the membrane due to the
shape change. The observed coexistence of coffee cups and sheet-like vesicles
were reproduced. Vesicles with two orifices were also analyzed and theoretically
reproduced.
PMID- 17030323
TI - Elastic control of electron transfer enthalpy and intensity of light absorption
by cupric blue proteins.
AB - The experimental data available shows that the change in enthalpy accompanying
electron transfer to cupric blue proteins decreases as the ratio of the strengths
of two visible light absorption bands increases. A compact mathematical
expression for this inverse relation is formulated, the derivation of which
demonstrates that the unusual geometry imposed by the protein upon the redox site
is responsible both for the optical band intensity ratio and for a significant
fraction of the enthalpy change.
PMID- 17030324
TI - Effect of aminophospholipid glycation on order parameter and hydration of
phospholipid bilayer.
AB - The effect of aminophospholipid glycation on lipid order and lipid bilayer
hydration was investigated using time-resolved fluorescence spectroscopy. The
changes of lipid bilayer hydration were estimated both from its effect on the
fluorescence lifetime of The 1-[4-(trimethylammonium)-phenyl]-6-phenylhexa-1,3,5
triene (TMA-DPH) and 1,6-diphenylhexa-1,3,5-triene (DPH) and using solvatochromic
shift studies with 1-anilinonaphthalene-8-sulfonic acid. The head-group and acyl
chain order were determined from time-resolved fluorescence anisotropy
measurements of the TMA-DPH and DPH. The suspensions of small unilamellar
vesicles (with phosphatidylethanolamine/phosphatidylcholine molar ratio 1:2.33)
were incubated with glyceraldehyde and it was found that aminophospholipids react
with glyceraldehyde to form products with the absorbance and the fluorescence
properties typical for protein advanced glycation end products. The lipid
glycation was accompanied by the progressive oxidative modification of
unsaturated fatty acid residues. It was found that aminophospholipid glycation
increased the head-group hydration and lipid order in both regions of the
membrane. The lipid oxidation accompanying the lipid glycation affected mainly
the lipid order, while the effect on the lipid hydration was small. The increase
in the lipid order was presumably the result of two effects: (1) the modification
of head-groups of phosphatidylethanolamine by glycation; and (2) the degradation
of unsaturated fatty acid residues by oxidation.
PMID- 17030325
TI - Partial molar volumes of some alpha-amino acids in aqueous sodium acetate
solutions at 308.15 K.
AB - The apparent molar volumes V(2,phi) have been determined for glycine, DL-alpha
alanine, DL-alpha-amino-n-butyric acid, DL-valine and DL-leucine in aqueous
solutions of 0.5, 1.0, 1.5 and 2.0 mol kg(-1) sodium acetate by density
measurements at 308.15 K. These data have been used to derive the infinite
dilution apparent molar volumes V(0)(2,phi) for the amino acids in aqueous sodium
acetate solutions and the standard volumes of transfer, Delta(t)V(0), of the
amino acids from water to aqueous sodium acetate solutions. It has been observed
that both V(0)(2,phi) and Delta(t)V(0) vary linearly with increasing number of
carbon atoms in the alkyl chain of the amino acids. These linear correlations
have been utilized to estimate the contributions of the charged end groups
(NH(3)(+), COO(-)), CH(2) group and other alkyl chains of the amino acids to
V(0)(2,phi) and Delta(t)V(0). The results show that V(0)(2,phi) values for
(NH(3)(+), COO(-)) groups increase with sodium acetate concentration, and those
for CH(2) are almost constant over the studied sodium acetate concentration
range. The transfer volume increases and the hydration number of the amino acids
decreases with increasing electrolyte concentrations. These facts indicate that
strong interactions occur between the ions of sodium acetate and the charged
centers of the amino acids. The volumetric interaction parameters of the amino
acids with sodium acetate were calculated in water. The pair interaction
parameters are found to be positive and decreased with increasing alkyl chain
length of the amino acids, suggesting that sodium acetate has a stronger
dehydration effect on amino acids which have longer hydrophobic alkyl chains.
These phenomena are discussed by means of the co-sphere overlap model.
PMID- 17030327
TI - Analysis of fibrous network fluid permeation data using the theory of
ultracentrifugation: application to fibrin gels.
AB - A new and alternative method for calculating the strand diameter of fibrous gel
networks from fluid permeation data is developed and used to analyze and compare
previous Darcy constant measurements of fibrin gels. The calculated diameters
from the various sets of experimental data using this method gives for a coarse
fibrin clot a strand diameter of approximately 1000 A and for a fine fibrin clot
a strand diameter of 170 A.
PMID- 17030326
TI - Conformational spectra--probing protein conformational changes.
AB - Stafford [Biophys. J. 17 (1996) MP452] has shown that it is possible, using the
analytical ultracentrifuge in sedimentation velocity mode, to calculate the
molecular weights of proteins with a precision of approximately 5%, by fitting
Gaussian distributions to g(s*) profiles so long as partial specific volume and
the radial position of the meniscus are known. This makes possible the analysis
of systems containing several components by the fitting of multiple distributions
to the total g(s*) profile. We have found the Stafford relationship to hold for a
range of protein solutes, particularly good agreement being found when the g(s*)
profiles are computed from Schlieren (dc/dr vs. r) data using the Bridgman
equation [J. Am. Chem. Soc. 64 (1942) 2349] . On this basis, we have developed a
new approach to the analysis of systems where two or more distinguishable
conformations of a single species are present, either in the same sample cell or
in different cells in the same rotor. In the former case, this allows us to
analyse a given solution of pure protein (i.e. monodisperse with respect to M) to
reveal the presence in that solution of two or more conformers under identical
solvent conditions. In the latter case, we can detect with high sensitivity any
conformational change occurring in the transition from one set of solvent
conditions to another. Alternatively, in this case, we can analyse slightly
different proteins (e.g. deletion mutants) for conformational changes under
identical solvent conditions. Examples of these procedures using well-defined
protein systems are given.
PMID- 17030328
TI - Ligand binding on ladder lattices.
AB - The ligand binding problems on two-dimensional ladders, which model many
important binding phenomena in molecular biology, are studied in details. The
model is represented by four parameters, the interactions between ligands when
bound to adjacent sites on opposite legs of the ladder (tau), the interactions
between bound ligands in the longitudinal direction of the ladder (sigma), the
number of binding sites that are covered by a bound ligand (m), and the intrinsic
binding constant (K). The partition functions of ring ladders are approached with
the transfer matrix method. A general relation is derived which connects the
partition function of a linear ladder with that of a ring ladder. The results
obtained apply to the general situation of multivalent binding, in which m>1.
Special attention is paid to the case where the ligand covers one site (m=1). In
this case explicit formulas are given for the partition functions of ring and
linear ladders. Closed-form expressions are obtained for various properties of
the system, including the degree of binding (theta), the midpoint in the binding
isotherm (1/square root(tau sigma)), the initial and end slopes of the Scatchard
plots (2sigma + tau - 4 and -sigma2 tau, respectively). From these closed-form
formulas, sigma and tau may be extracted from experimental data. The model
reveals certain features which do not exist in one-dimensional models. Using the
general method discussed in [1], the recurrence relation is found for the
partition functions. The analytical solution found for this model provides test
cases to verify the numerical results for more complex two-dimensional models.
PMID- 17030329
TI - Effects of alcohols on lipid bilayers with and without cholesterol: the
dipalmitoylphosphatidylcholine system.
AB - Differential scanning calorimetry is a useful method to study the thermotropic
phase transitions of a phospholipid bilayer. In the present study DSC is used to
determine the effects of methanol and ethanol on DPPC and DPPC/2 mol% cholesterol
bilayers. The biphasic effect of the main transition and the presence of an extra
peak on the DSC cooling scans were observed above certain alcohol concentrations.
In the presence of 2% cholesterol, the concentration at which the biphasic effect
occurs is increased by both short-chain alcohols. 1,6-Diphenyl-1,3,5-hexatriene
(DPH) is used as a fluorescent probe to directly determine the onset of
interdigitation in these systems as reflected by a drop in the DPH fluorescence
intensity.
PMID- 17030330
TI - Conformation of poly(methacrylic acid) in acidic aqueous solution studied by
small angle X-ray scattering.
AB - The nature of the contracted form of poly(methacrylic acid) PMA chain in salt
free acidic aqueous solution was studied by analyzing scattering curves
registered by small-angle X-ray scattering, comparing it with those of PMA in
methanol at 26 degrees C and of partially neutralized PMA in aqueous solution
containing added salt (the concentration of added salt, Cs=0.1 M NaF). It is
shown that the distribution of segments in the contracted form as well as that of
PMA in methanol is that of a random-coil in a theta medium and that this
distribution of segments is stable over a fair range of degrees of ionization
alpha for Cs below 0.1 M. Moreover, the persistence length of PMA at Cs=0.1 M
(4+/-0.5 A) is substantially constant throughout the entire range of alpha,
indicating that the contracted form of PMA changes to an expanded random-coil in
a higher pH region without a significant change in the chain flexibility.
PMID- 17030331
TI - The role of conformational energetic disorder in the catalytic activity of
immobilized enzymes.
AB - We analyze cooperative behavior in a system of immobilized enzymes which
incorporates the notion of heterogeneity or disorder in the interactions. In
addition to equilibrium phase changes, this system exhibits vitrification or
glass-like transitions in which the overall catalytic activity freezes into one
of many possible states. It is shown that these long-lived metastable phases can
be produced by a combination of disorder, systematic surface and intermolecular
interactions, and chemical association effects such as ligand binding.
Biophysical consequences of this frozen state include greatly diminished
sensitivity of enzymatic activity to thermal and chemical perturbations. This
effect coincides with the appearance of a multitude of possible macroscopic
catalytic states rather than a single equilibrium state. Our analysis also
suggests that high surface coverages will tend to be catalytically inactive if
they are fully equilibrated; rather, high activity with high surface coverage is
more likely to be associated with vitrified states of surface immobilization and
deep or abrupt chemical quenches.
PMID- 17030332
TI - Physico-chemical aspects of the interaction between DNA and oppositely charged
mixed liposomes.
AB - The mechanism of complex formation between DNA and oppositely charged
dioctadecyldimethylammonium bromide/dioleoyl phosphatidylethanolamine
(DODAB/DOPE) and 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)/DOPE mixed
liposomes, as well as the physico-chemical properties of DNA-mixed liposome
complexes, were examined. Fluorescence microscopy showed that the interaction
between DNA and oppositely charged mixed liposomes started at very low liposome
concentrations and induced a discrete coil-globule transition in individual DNA
molecules. The DNA size distribution was bimodal in a wide range of liposome
concentrations. The critical concentration of the cationic lipid needed for the
complete compaction of single DNA molecules depended on the composition of the
charged mixed DODAB/DOPE and DOTAP/DOPE liposomes. Cryogenic transmission
electron microscopy (cryo-TEM) observations of DNA complexes with mixed liposomes
revealed that the lamellar packing of lipid molecules was typical for the
complexes formed from the cationic lipid-enriched mixtures, while inverted
hexagonal arrays were found for the neutral lipid-enriched complexes. The
microstructures of the complexes were also examined with the use of the small
angle X-ray scattering (SAXS) technique, which confirmed the results obtained by
cryo-TE microscopy and enabled the quantitative characterization of lipid
packaging in the complexes with DNA macromolecules. We also found that the
introduction of the neutral lipid into the complexes between DNA and oppositely
charged lipids, DODAB and DOTAP, moderately increased the thermal stability of
the complexes and changed the quantitative characteristics of the melting
profiles of the complexes.
PMID- 17030333
TI - Hydrophobic thickness of fluid planar monooleylglycerol membranes maximally
thinned by inversed micellisation.
AB - A procedure of making membranes of amphiphilic materials at the bottom of a U
shaped flexible plastic tube within an aqueous medium is described. The membranes
were made sufficiently large in order for the annulus area to be neglected.
Consequently the hydrophobic thickness of the membrane could be measured by a
capacitance technique assuming the relative permittivity of the hydrophobic part
of the bilayer. Introduction of an AC microvolt technique allowed manufacture of
stable thick membranes by quenching the electroconstriction observed when DC
electrical potentials in the millivolt range are used. By continuously monitoring
the hydrophobic thickness and by use of the AC microvolt technique the membrane
thinning process by chemical means could be studied in isolation because the
electroconstriction was quenched. The maximally thinned hydrophobic thickness of
a monooleylglycerol membrane measured at 38 degrees C was found to be 25+/-1.2 A.
Criteria and argumentation for maximal thinning of the membrane are put forward.
A distinction between genuine and modified cholesterol was demonstrated to be
possible by the described method.
PMID- 17030334
TI - Effects of solvents interacting favorably with hydrophilic segments of the
membrane surface of phosphatidylcholine on their gel-phase membranes in water.
AB - We have investigated the effects of two kinds of solvents forming the lamellar
liquid-crystalline (L(alpha)) phase in phosphatidylcholine (PC) membranes in neat
condition, such as formamide and 1,3-propanediol, on phase behaviors of
multilamellar vesicle (MLV) of DPPC (DPPC-MLV). These solvents induced the
interdigitated gel (L(beta)I) phase in DPPC-MLV in excess water above their
critical concentrations. Solubility measurement indicates that these solvents
interact favorably with the hydrophilic segment of the PC membrane but interact
unfavorably with the alkyl chains. Based on these results, we propose the
mechanism of the induction of the L(beta)I phase by these solvents.
PMID- 17030335
TI - Molecular dynamics simulations of Cu,Zn superoxide dismutase: effect of
temperature on dimer asymmetry.
AB - Molecular dynamics simulations of solvated dimeric Cu,Zn superoxide dismutase
have been carried out at four temperatures, namely 200, 225, 250 and 300 K.
Analysis of the backbone-to-backbone hydrogen bonds number indicates that the
symmetry observed in the two subunits at 200 K is gradually lost by heating the
system. The C(alpha) atoms displacement cross-correlation maps confirm that the
asymmetric behaviour of the two subunits increases as a function of temperature.
The dynamic cross-correlation of the subunits volumes indicates a fast
correlation between the two subunits at 300 K, which is delayed upon lowering the
simulation temperature. These results indicate that temperature plays an
essential role in injecting such an asymmetry; the two subunits being asymmetric
and in rapid communication at 300 K, and almost symmetric and in slow
communication at lower temperatures.
PMID- 17030336
TI - RNA switches the higher-order structure of DNA.
AB - By the direct observation of single duplex DNA molecules by fluorescence
microscopy, we found that RNA molecules have the potential to change discretely
the higher-order structure of individual DNA molecules between the compact and
elongated states. We performed an experiment with a linear giant DNA (T4 DNA, 166
kbp) and a circular DNA (cosmid vector, 42 kbp), and examined the effect of
single-strand RNA on their conformations under a physiological concentration of
spermidine. Individual DNA chains compacted by spermidine were elongated in an
abrupt manner with an increase in the RNA concentration. This finding is
discussed in view of the effect of the interplay between the dynamics of
chromosomal DNA and the production of RNA in the cytoplasmic environment.
PMID- 17030337
TI - A molecular dynamics simulation study of the solvent isotope effect on copper
plastocyanin.
AB - The effect of heavy water on the structure and dynamics of copper plastocyanin as
well as on some aspects of the solvent dynamics at the protein-solvent
interfacial region have been investigated by molecular dynamics simulation. The
simulated system has been analyzed in terms of the atomic root mean square
deviation and fluctuations, intraprotein H-bond pattern, dynamical cross
correlation map and the results have been compared with those previously obtained
for plastocyanin in H2O (Ciocchetti et al. Biophys. Chem. 69 (1997), 185-198).
The simulated plastocyanin structure in the two solvents, averaging 1 ns, is very
similar along the beta-structure regions, while the most significant differences
are registered, analogous to the turns and the regions likely involved in the
electron transfer pathway. Moreover, plastocyanin in D2O shows an increase in the
number of both the intraprotein H-bonds and the residues involved in correlated
motions. An analysis of the protein-solvent coupling evidenced that D2O makes the
H-bond formation more difficult with the solvent molecules for positively charged
and polar residues, while an opposite trend is observed for negatively charged
residues. On the other hand, the frequency of exchange of the solvent molecules
involved in the protein-solvent H-bond formation is significantly depressed in
D2O. The results are discussed also in connection with protein functionality and
briefly with some experimental results connected with the thermostability of
proteins in D2O.
PMID- 17030338
TI - Modulation of cellular rhythm and photoavoidance by oscillatory irradiation in
the Physarum plasmodium.
AB - We studied responses of cellular rhythm and light-induced movement to periodic
irradiation in a unicellular amoeboid organism, the Physarum plasmodium. The
intrinsic frequency of the contraction rhythm, which is based on biochemical
oscillations, became synchronized with the frequency of periodic irradiation with
light when both frequencies were close enough. In order to study the role of the
synchronization in light-induced movement, periodic irradiation was applied to
only part of the plasmodium. The rate of avoidance of light was modulated in the
frequency band in which the synchronization occurred. The synchronization
property of the contraction oscillation underlies the regulation of tactic
movement in plasmodium.
PMID- 17030339
TI - Partial molar volumes of proteins: amino acid side-chain contributions derived
from the partial molar volumes of some tripeptides over the temperature range 10
90 degrees C.
AB - The partial molar volumes of tripeptides of sequence glycyl-X-glycine, where X is
one of the amino acids alanine, leucine, threonine, glutamine, phenylalanine,
histidine, cysteine, proline, glutamic acid, and arginine, have been determined
in aqueous solution over the temperature range 10-90 degrees C using differential
scanning densitometry . These data, together with those reported previously, have
been used to derive the partial molar volumes of the side-chains of all 20 amino
acids. The side-chain volumes are critically compared with literature values
derived using partial molar volumes for alternative model compounds. The new
amino acid side-chain volumes, along with that for the backbone glycyl group,
were used to calculate the partial specific volumes of several proteins in
aqueous solution. The results obtained are compared with those observed
experimentally. The new side-chain volumes have also been used to re-determine
residue volume changes upon protein folding.
PMID- 17030340
TI - Hydrophobicity of benzene.
AB - The present work tries to clarify the molecular origin of the poor solubility of
benzene in water. The transfer of benzene from pure liquid phase into water is
dissected in two processes: transfer from gas phase to pure liquid benzene; and
transfer from gas phase to liquid water. The two solvation processes are analyzed
in the temperature range 5-100 degrees C according to Lee's Theory. The solvation
Gibbs energy change is determined by the balance between the work of cavity
creation in the solvent, and the dispersive interactions of the inserted benzene
molecule with the surrounding solvent molecules. The purely structural solvent
reorganization upon solute insertion proves to be a compensating process. The
analysis shows that the work of cavity creation is larger in water than in
benzene, whereas the attractive energetic interactions are stronger in benzene
than in water; this scenario is true at any temperature. Therefore, both terms
act in the same direction, contrasting the transfer of benzene from pure liquid
phase into water and determining its hydrophobicity.
PMID- 17030342
TI - Two-dimensional receptor patterns in the plasma membrane of cells. A critical
evaluation of their identification, origin and information content.
AB - A concise review is presented on the nature, possible origin and functional
significance of cell surface receptor patterns in the plasma membrane of lymphoid
cells. A special emphasize has been laid on the available methodological
approaches, their individual virtues and sources of errors. Fluorescence energy
transfer is one of the oldest available means for studying non-randomized co
distribution patterns of cell surface receptors. A detailed and critical
description is given on the generation of two-dimensional cell surface receptor
patterns based on pair-wise energy transfer measurements. A second hierarchical
level of receptor clusters have been described by electron and scanning force
microscopies after immuno-gold-labeling of distinct receptor kinds. The origin of
these receptor islands at a nanometer scale and island groups at a higher
hierarchical (mum) level, has been explained mostly by detergent insoluble
glycolipid-enriched complexes known as rafts, or detergent insoluble glycolipids
(DIGs). These rafts are the most-likely organizational forces behind at least
some kind of receptor clustering [K. Simons et al., Nature 387 (1997) 569]. These
models, which have great significance in trans-membrane signaling and intra
membrane and intracellular trafficking, are accentuating the necessity to revisit
the Singer-Nicolson fluid mosaic membrane model and substitute the free protein
diffusion with a restricted diffusion concept [S.J. Singer et al., Science 175
(1972) 720].
PMID- 17030343
TI - Fluorescence correlation spectroscopy analysis of the hydrophobic interactions of
protein 4.1 with phosphatidyl serine liposomes.
AB - Fluorescence correlation spectroscopy (FCS) was applied to examine the
interactions between a protein and a membrane lipid. The protein 4.1-phosphatidyl
serine (PS) interactions served as the model system to demonstrate the membrane
lipid-protein interactions. This protein was labeled with rhodamine and its
interactions with PS-liposomes were measured by FCS. The present results clearly
demonstrated that a small protein molecule, protein 4.1, interacts specifically
with a large particle, a PS-liposome. This interaction appears to be hydrophobic
and not electrostatic, since the bound protein 4.1 did not dissociate in solution
and was specifically released from PS-liposomes by treatment with phospholipase
A(2) (PLA(2)). In the present study, using FCS we could demonstrate that the
serine residue of PS is required for protein 4.1 to bind to PS-liposomes and that
the bound protein 4.1 is closely associated with the fatty acid of the PS
molecule in the liposomes.
PMID- 17030344
TI - Regulation of the ryanodine receptor calcium release channel: a molecular complex
system.
AB - Skeletal muscle contraction is regulated by Ca(2+) released from the sarcoplasmic
reticulum (SR). The Ca(2+) release channel in the SR has been identified as the
ryanodine receptor (RyR). Recently, it was found that the RyR is a large
transmembrane protein that is regulated by many intrinsic factors. In this
review, we mainly summarize our experimental results. We will first show that
calsequestrin and the DIDS-binding 30-kDa protein work as intrinsic factors and
regulate the RyR Ca(2+) release channel. Next, the DIDS-binding 30-kDa protein
was identified as the ADT/ATP translocase (AAT) present in mitochondria, based on
a cDNA analysis. This result shows that AAT is bifunctional and works as a
transporter protein in mitochondria and as a regulator of Ca(2+) release in the
SR. From these results, we propose a model in which calsequestrin, the DIDS
binding 30-kDa protein, and junctin form a ternary complex that regulates the RyR
Ca(2+) release channel through interactions with triadin.
PMID- 17030345
TI - Accelerated diffusion of Na(+) in a hydrophobic region revealed by molecular
dynamics simulations of a synthetic ion channel.
AB - To get insight into the significance of the hydrophobic lining on the ion
permeation, we performed molecular dynamics simulations on a Na(+) permeation
through a de novo synthetic hydrophobic channel. Electrophysiological study has
suggested that the channel is formed from a tail-to-tail associated dimer of a
cyclic octa-peptide coupled with hydrophobic acyl chains. The acyl chains line
the channel pore while the cyclic peptide forms the channel entrance [Z. Qi, M.
Sokabe, K. Donowaki, H. Ishida, Biophys. J. 76 (1999) 631]. Molecular dynamics
simulation of water in the channel indicated that the inferred structure is
physically reasonable [Z. Qi, M. Sokabe, Biophys. Chem. 71 (1998) 35]. In the
present study, the potential energy profile of the Na(+) and the energy
contributions from each component of the system at different positions along the
channel axis were calculated. An energy well instead of a peak is located at the
central hydrophobic cavity of the channel, due to its ability of accommodating at
least five water molecules to hydrate the ion. Interestingly, the ion diffuses
much faster in the hydrophobic acyl chain region, particularly in the central
hydrophobic cavity, than it does in the peptide ring region and even surprisingly
faster than that in the bulk phase. These results provide a physical basis for an
idea that the hydrophobic lining of the K(+) channel [D.A. Doyle, J.M. Cabral,
R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, R. MacKinnon,
Science 280 (1998) 69] plays an active role to facilitate the ion permeation
through the channel pore.
PMID- 17030346
TI - Quantitative Western blot analysis of plasma ADAMTS13 antigen in patients with
Upshaw-Schulman syndrome.
PMID- 17030347
TI - Hypertension in cardiopulmonary bypass: a sign of insufficient anticoagulation in
a patient undergoing surgical resection of myxoma.
PMID- 17030348
TI - Vertical migration studies of 137Cs from nuclear weapons fallout and the
Chernobyl accident.
AB - The vertical migration of (137)Cs originating from nuclear weapons fallout (NWF)
and the Chernobyl accident has been studied at 33 sampling sites in western
Sweden. An attempt to describe the present depth distribution with a solution to
the convection-diffusion equation (CDE) with a pulse-like fallout event as the
initial condition was made. A sum of two CDEs describing the NWF and Chernobyl
debris was fitted to the actual depth profiles measured by soil sampling. The
fitted depth profiles were used to correct in situ measurements for the actual
depth distribution, showing good agreement with the accumulated activities in
soil samples. As expected, the vertical migration was very slow and most caesium
was still present in the upper soil layers. The ranges of the apparent convection
velocity, v, and apparent diffusion coefficient, D, were between 0 and 0.35
cm/year and 0.06 and 2.63 cm(2)/year, respectively.
PMID- 17030349
TI - L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in
ovarian carcinoma cells.
AB - OBJECTIVE: Apoptosis resistance is a hallmark of cancer progression, a phenomenon
frequently observed in ovarian carcinoma. We reported previously, that L1
adhesion molecule (CD171) is overexpressed in ovarian and endometrial carcinomas
and that L1 expression is a predictor of poor outcome. We investigated a possible
role of L1 in apoptosis resistance. METHODS: We used L1 transfectants and ovarian
carcinoma cell lines and induced apoptosis by different stimuli such as C2
ceramide, staurosporine, cisplatin or hypoxia. RESULTS: We found that cells
expressing L1 are more resistant against apoptosis. In HEK293 cells, L1
expresssion leads to a sustained ERK, FAK and PAK phosphorylation. Soluble L1
only partially rescued HEK293 cells from apoptosis. Treatment with apoptotic
stimuli upregulated the anti-apoptotic molecule Bcl-2 to a greater extend in
HEK293 cells expressing L1. In the ovarian carcinoma cell line OVMz, the
depletion of L1 by RNA interference sensitized cells for apoptosis induction. No
changes in activation of ERK or FAK were observed after L1 knockdown. The
selection of m130 ovarian carcinoma or SW707 colon carcinoma cells with cisplatin
leads to upregulated expression of L1. CONCLUSIONS: Our results suggest a link
between L1 expression and chemoresistance of ovarian carcinomas. Upregulation of
L1 after cisplatin treatment might indicate a more malignant tumor phenotype
given the established role of L1 in cell motility and invasion.
PMID- 17030350
TI - Heparanase expression correlates with poor survival in metastatic ovarian
carcinoma.
AB - OBJECTIVE: To analyze the expression of Heparanase, an enzyme involved in cancer
metastasis and angiogenesis, in ovarian and breast carcinoma cells in effusions.
METHODS: Heparanase protein expression was analyzed in malignant effusions from
ovarian (=200) and breast (=41) carcinoma patients using immunocytochemistry. The
levels of secreted heparanase were analyzed in 45 effusion supernatants using a
newly established ELISA test. Heparanase expression levels were analyzed for
clinical significance. RESULTS: Heparanase was expressed at the cell membrane in
106/200 (53%) ovarian and 22/41 (54%) breast carcinomas. Cytoplasmic expression
was found in 180/200 (90%) ovarian and 26/41 (63%) breast carcinomas. Reactive
mesothelial cells showed frequent cytoplasmic, but not membrane expression. ELISA
showed secreted heparanase in all 45 analyzed effusions. Higher levels were
detected in peritoneal compared to pleural effusions (p=0.031). In univariate
survival analysis of ovarian carcinoma patients with post-chemotherapy effusions,
membrane expression in >5% of tumor cells correlated with shorter overall
survival (OS, p=0.013). FIGO stage (p=0.03 for all patients, p=0.045 for those
with post-chemotherapy specimens) and response to first-line chemotherapy
(p<0.0001 for all patients, p=0.049 for those with post-chemotherapy specimens)
were the clinical parameters related to OS. In Cox analysis of this subset of
patients, heparanase expression (p=0.02) and response to chemotherapy (p=0.049)
were independent predictors of poor OS. Heparanase expression did not correlate
with survival in breast carcinoma. CONCLUSIONS: Our data show that heparanase is
frequently expressed in metastatic gynecologic adenocarcinomas, and that it is
secreted into the effusion fluid in body cavities. The correlation between
heparanase expression and poor survival in ovarian carcinoma suggests a role for
this molecule in ovarian cancer metastasis and supports its role as a marker of
aggressive clinical behavior at disease recurrence.
PMID- 17030351
TI - COX-2 and survivin are overexpressed and positively correlated in endometrial
carcinoma.
AB - OBJECTIVES: To investigate the expressions of survivin and Cyclooxygenase-2 (COX
2), and their possible correlations in the development of endometrial
adenocarcinoma (EC). We also looked at their association with classical
prognostic factors in EC. To our knowledge, this is the first time survivin
expression is investigated in terms of its relation to COX-2 in the developmental
pathway of EC. METHODS: Archived tissue samples of 50 EC, 30 endometrial
hyperplasia and 20 proliferative endometrium were selected and
immunohistochemically analyzed for survivin and COX-2 expression. RESULTS: Both
survivin and COX-2 were overexpressed in hyperplasia and endometrial
adenocarcinoma cases compared to proliferative endometrium, which was
statistically significant (p=0.01, p=0.02, respectively). Among EC cases,
survivin and COX-2 were strongly positive in 38 (76%) and 30 (60%) patients,
respectively. Furthermore, we found survivin and COX-2 to be positively
correlated, which was also statistically significant (p=0.0001, r=0.46). Neither
survivin nor COX-2 expression was correlated with classical prognostic factors of
endometrial carcinoma such as myometrial invasion, grade or lymph node metastasis
(p>0.05). Neither COX-2 nor survivin had an impact on overall survival (p>0.05).
CONCLUSIONS: Both survivin and COX-2 are overexpressed, and they seem to be early
events in the occurrence of EC. Moreover, protein products of these two genes are
positively correlated. COX-2 and survivin might share a common molecular pathway
or enhance each other's actions in the developmental pathway of EC. Molecular
basis of such a relationship should be further investigated in endometrial
carcinogenesis.
PMID- 17030352
TI - Expression of class III beta tubulin in cervical cancer patients administered
preoperative radiochemotherapy: correlation with response to treatment and
clinical outcome.
AB - OBJECTIVES: Alterations of the beta subunit of tubulin have been reported to be
predictive of resistance to radiation and antitubulin agents in several solid
tumors. The aim of the study was to investigate the clinical role of beta III
tubulin expression as prognostic factor for survival and as a predictive
parameter of response to preoperative radiochemotherapy in a single institutional
series of locally advanced cervical cancer (LACC) patients. METHODS: The study
included 98 LACC patients admitted to the Gynecologic Oncology Unit, Catholic
University of Rome and Campobasso between January 1998 and January 2005.
Immunohistochemistry was performed by using the polyclonal rabbit anti-beta III
tubulin antibody (Covance, Princeton, NJ, USA). The value of 10% immunostained
tumor cells was arbitrarily chosen as cut-off value to distinguish cases with
high versus low beta III tubulin content. RESULTS: In the whole series, beta III
tubulin immunoreaction was detectable in 66/98 cases (67.3%), and the percentage
of positively stained cells ranged from 0 to 100% (median=10%). The percentages
of cases with high beta III tubulin expression were shown not to be differently
distributed according to clinico-pathological characteristics. There was no
statistically significant difference in the distribution of cases with high beta
III tubulin expression according to clinical and pathological response to
treatment. During the follow-up period, recurrence and death of disease occurred
in 15 and 13 cases, respectively. There was no difference in disease-free and
overall survival in cases with high versus low beta III tubulin expression.
CONCLUSIONS: The assessment of class III beta tubulin status seems of little
usefulness in order to identify LACC patients with poor chance of response to
concomitant radiochemotherapy and unfavorable prognosis.
PMID- 17030353
TI - The impact of age in the outcome of patients with advanced or recurrent cervical
cancer after platinum-based chemotherapy.
AB - OBJECTIVES: Cervical cancer is a disease of middle-aged and elderly but still
there are young women diagnosed with advanced disease that is incurable with
local treatment and is treated with platinum-based combination chemotherapy. It
is unknown whether these young patients have a poorer outcome compared to older
patients or whether elderly patients have inferior outcome than younger patients
when treated with combination chemotherapy. METHODS: We compared the outcome
between young (<35), elderly (>70) and middle-aged (35-70) women who were treated
with platinum-based combination chemotherapy for advanced, recurrent or
persistent disease. RESULTS: Two hundred and eighteen patients were included in
our database. The baseline clinical and disease characteristics were not
different between age groups but anemia and thrombocytosis were more frequent in
younger patients. Median survival for all patients was 13.4 (95%CI 11-15.8)
months while survival of patients<35 years of age was 9 months (95% CI 5.8-12),
of patients older than 70 was 10 months (95% CI 6.9-13) of patients 35 to 70
years of age was 14.5 months (95% CI 11-18) (p=0.004). Multiple factors were
significant for survival in univariate analysis but only weight loss, pain score
and relapse inside an irradiated filed were significant predictors of outcome in
multivariate analysis. CONCLUSIONS: Very young (<35) and elderly (>70) patients
have a worse prognosis after treatment with combination chemotherapy for advanced
or recurrent cervical cancer. Nevertheless, this difference is not significant
when adjusted for other prognostic factors.
PMID- 17030354
TI - Prognostic factors responsible for survival in sex cord stromal tumors of the
ovary--an analysis of 376 women.
AB - OBJECTIVE: To evaluate prognostic factors that impact on the survival of women
with ovarian sex cord stromal tumors (SCST). METHODS: Data including age at
diagnosis, stage, histology, grade, treatment, and survival were extracted from
the 1988-2001 Surveillance, Epidemiology, and End Results Program. Kaplan-Meier
and Cox proportional hazards analyses were used to determine the predictors for
survival. RESULTS: 376 women (median age: 51) with ovarian sex cord stromal cell
tumors were identified, including 339 with granulosa cell and 37 with Sertoli
Leydig cell tumors. 265 (71%) patients had stage I, 39 (10%) stage II, 40 (11%)
stage III, and 32 (8%) had stage IV disease. Women with stage I-II disease had a
5-year disease-specific survival of 95% compared to 59% in those with stage III
IV cancers (p<0.001). Patients50
years (93% vs. 84%, p<0.001). This age-associated survival advantage was observed
for early (97% vs. 92%, p=0.003), but not for advanced-staged (68% vs. 53%,
p=0.09) patients. 110 patients with stage I-II disease underwent conservative
surgery without hysterectomy. The survival for this group was similar to patients
who underwent a standard surgery including a hysterectomy (94.8% and 94.9%,
p=0.38). On multivariate analysis, age0.05)
between PAL (14.7%; 38/258) and NPAL (13.4%; 35/262). In conclusion, PPR between
days 34 and 41 of pregnancy using the fetal membrane slip technique did not
affect embryo/fetal viability.
PMID- 17030360
TI - Influence of arginine-glycine-aspartic acid (RGD), integrins (alphaV and alpha5)
and osteopontin on bovine sperm-egg binding, and fertilization in vitro.
AB - Osteopontin (OPN), a phosphoprotein containing an arginine-glycine-aspartic acid
(RGD) sequence, has been identified in cow oviduct epithelium and fluid. To
investigate the potential role OPN in fertilization, we evaluated the ability of
RGD peptide (arginine-glycine-aspartic), RGE peptide (arginine-glycine-glutamic
acid), integrins alphaV and alpha5 antibodies and OPN antibody to influence
bovine in vitro sperm-egg binding and fertilization. Treatment of sperm or
oocytes with the RGD peptide prior fertilization significantly decreased in vitro
sperm-egg binding and fertilization compared to the non-treated controls or those
treated with RGE peptide. Binding and fertilization were also significantly
decreased when in vitro matured bovine oocytes or sperm were pre-incubated with
integrins alphaV and alpha5 antibodies at concentration ranging from 5 to 20
microg/mL. Addition of a rabbit polyclonal IgG antibody against purified bovine
milk OPN with sperm or/and oocytes decreased (P<0.05) fertilization compared to
the in vitro-fertilized control. These data provided evidence that integrin
ligands existed on bovine oocytes and spermatozoa that contained RGD recognition
sequences, and that antibody to OPN, a protein that contains that RGD sequence,
was capable of reducing sperm-egg binding and fertilization in vitro.
PMID- 17030362
TI - Multi-spectroscopic study on interaction of bovine serum albumin with
lomefloxacin-copper(II) complex.
AB - The binding reactions of lomefloxacin-copper(II) complex (LMF-Cu) or LMF to
bovine serum albumin (BSA) in physiological solution were investigated by multi
spectroscopy. The binding constant, the number of binding sites and the binding
distance between LMF-Cu or LMF and BSA were obtained by a fluorescence quenching
method and according to the mechanism of Forster-type dipole-dipole non
radioactive energy-transfer, respectively. Enthalpy and entropy changes for two
systems were calculated to be -7.970 kJ mol(-1) and 47.438 J mol(-1)K(-1) for LMF
BSA, -12.469 kJ mol(-1) and 33.542 J mol(-1)K(-1) for LMF-Cu-BSA, respectively.
The highly positive values observed for the entropy give evidence for a strong
interaction. The values of DeltaH and DeltaS in two systems are similar,
indicating that electrostatic interactions in two systems play major role. The
effect of LMF-Cu or LMF on the conformation of BSA was also analyzed by
synchronous fluorescence, three-dimensional fluorescence and circular dichroism
spectra. The results showed that the presence of Cu ion in LMF-Cu can affect the
conformation of BSA to some degree. All the results revealed that the addition of
copper ion promotes the interaction of lomefloxacin with bovine serum albumin.
PMID- 17030361
TI - Butyrolactone I reversibly alters nuclear configuration, periooplasmic
microtubules and development of porcine oocytes.
AB - In the present study, we investigated the effects of specific cdc2 kinase
inhibitor, butyrolactone I (BL I) on the prevention of germinal vesicle
breakdown, changes of microtubular structures, and development of porcine oocytes
after removal of the drug. In Experiment 1, cumulus-oocyte complexes (COCs) were
cultured (44 h) in NCSU-23 medium containing different concentrations of BL I.
The percentages of oocytes remaining at GV stage were 0, 0, 32, 80, and 84%
(P<0.05), and the maturation rates were 86, 63, 30, 0, and 0% (P<0.05) for
oocytes treated with 0, 10, 20, 40, and 80 microM of BL I, respectively. When
oocytes were released from BL I incubation (Experiment 2) and cultured for an
additional 44 h, 79, 84, and 83% of oocytes resumed meiosis, but only 52, 38 and
17% of oocytes reached normal metaphase II (MII) stage in the groups treated with
20, 40 and 80 microM BL I, respectively. In Experiments 3-5, reversibility and
development of oocytes and embryos were evaluated after removal of the inhibitor.
A reduced duration of BL I incubation (22 h) at 20 microM increased the
percentage of oocytes remaining at the GV stage compared to the control group
(85% versus 9%, P<0.05). Blastocyst rates were lower in treatment groups than in
the control (44 h) group (0-14% versus 24%; P<0.05). However, all developing
blastocysts possessed similar cell numbers, regardless of the drug-treated or non
treated controls. Taken together, treatment with 20-80 microM of BL I effectively
prevented the resumption of meiosis and polymerization of periooplasmic
microtubules. Furthermore, reversibility of the oocytes after reduced duration of
BL I treatment was satisfactory.
PMID- 17030363
TI - Glycosaminoglycan-targeted fixation for improved bioprosthetic heart valve
stabilization.
AB - Numerous crosslinking chemistries and methodologies have been investigated as
alternative fixatives to glutaraldehyde (GLUT) for the stabilization of
bioprosthetic heart valves (BHVs). Particular attention has been paid to valve
leaflet collagen and elastin stability following fixation. However, the stability
of glycosaminoglycans (GAGs), the primary component of the spongiosa layer of the
BHV, has been largely overlooked despite recent evidence provided by our group
illustrating their structural and functional importance. In the present study we
investigate the ability of two different crosslinking chemistries: sodium
metaperiodate (NaIO(4)) followed by GLUT (PG) and 1-Ethyl-3-(3
dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) followed by GLUT
(ENG) to stabilize GAGs within BHV leaflets and compare resulting leaflet
characteristics with that of GLUT-treated tissue. Incubation of fixed leaflets in
GAG-degrading enzymes illustrated in vitro resistance of GAGs towards degradation
in PG and ENG treated tissue while GLUT fixation alone was not effective in
preventing GAG loss from BHV leaflets. Following subdermal implantation,
significant amounts of GAGs were retained in leaflets in the ENG group in
comparison to GLUT-treated tissue, although GAG loss was evident in all groups.
Utilizing GAG-targeted fixation did not alter calcification potential of the
leaflets while collagen stability was maintained at levels similar to that
observed in conventional GLUT-treated tissue.
PMID- 17030364
TI - On the presence of enriched amounts of 235U in hot particles from the terrestrial
area affected by the Palomares accident (Spain).
AB - The characterisation by ICP-MS of an isolated Pu-U hot particle originating from
the nuclear weapons accident in Palomares (Spain) shows, for the first time, that
its uranium content is highly enriched in (235)U. The enrichment has been
confirmed by independent analyses of two surface soil samples collected in a
heavily contaminated area close to the impact point of one of the bombs. This
finding clarifies better the composition of the weapons involved in the accident
and is of importance when the inventory of U and Pu in the contaminated area are
to be calculated.
PMID- 17030365
TI - Magnetic approach to normalizing heavy metal concentrations for particle size
effects in intertidal sediments in the Yangtze Estuary, China.
AB - In this study, mineral magnetic, particle size and geochemical analyses were
conducted on intertidal sediments from the Yangtze Estuary to examine the
feasibility of heavy metal concentrations normalization using magnetic
techniques. Susceptibility of Anhysteretic Remanent Magnetization (chiARM), the
ratio of chiARM to SIRM (Saturation Isothermal Remanent Magnetization) and
susceptibility (chiARM/SIRM and chiARM/chi, respectively), and to a lesser
degree, frequency dependent susceptibility (chifd), displayed significant
correlations with the fine sediment fraction (<16 microm). The strong
relationships between chiARM and heavy metals can be explained by the role of
particle size and iron oxides in controlling metal concentrations. This study
demonstrates that chiARM can be used to normalize for particle size effects as
efficiently as common reference elements such as Al. Furthermore, the rapid and
non-destructive nature of mineral magnetic measurement technique means that
chiARM has a considerable application value in environmental quality monitoring
and related studies.
PMID- 17030366
TI - Calcium microdomains: organization and function.
AB - Microdomains of Ca(2+), which are formed at sites where Ca(2+) enters the
cytoplasm either at the cell surface or at the internal stores, are a key element
of Ca(2+) signalling. The term microdomain includes the elementary events that
are the basic building blocks of Ca(2+) signals. As Ca(2+) enters the cytoplasm,
it produces a local plume of Ca(2+) that has been given different names (sparks,
puffs, sparklets and syntillas). These elementary events can combine to produce
larger microdomains. The significance of these localized domains of Ca(2+) is
that they can regulate specific cellular processes in different regions of the
cell. Such microdomains are particularly evident in neurons where both pre- and
postsynaptic events are controlled by highly localized pulses of Ca(2+). The
ability of single neurons to process enormous amounts of information depends upon
such miniaturization of the Ca(2+) signalling system. Control of cardiac cell
contraction and gene transcription provides another example of how the parallel
processing of Ca(2+) signalling can occur through microdomains of intracellular
Ca(2+).
PMID- 17030367
TI - Ca2+ microdomains and the control of insulin secretion.
AB - Nutrient-induced increases in intracellular free Ca(2+) concentrations are the
key trigger for insulin release from pancreatic islet beta-cells. These Ca(2+)
changes are tightly regulated temporally, occurring as Ca(2+) influx-dependent
baseline oscillations. We explore here the concept that locally high [Ca(2+)]
concentrations (i.e. Ca(2+) microdomains) may control exocytosis via the
recruitment of key effector proteins to sites of exocytosis. Importantly, recent
advances in the development of organelle- and membrane-targeted green fluorescent
protein (GFP-) or aequorin-based Ca(2+) indicators, as well as in rapid imaging
techniques, are providing new insights into the potential role of these Ca(2+)
microdomains in beta-cells. We summarise here some of the evidence indicating
that Ca(2+) microdomains beneath the plasma membrane and at the surface of large
dense core vesicles may be important in the normal regulation of insulin
secretion, and may conceivably contribute to "ATP-sensitive K(+)-channel
independent" effects of glucose. We also discuss evidence that, in contrast to
certain non-excitable cells, direct transfer of Ca(2+) from the ER to
mitochondria via localised physical contacts between these organelles is
relatively less important for efficient mitochondrial Ca(2+) uptake in beta
cells. Finally, we discuss evidence from single cell imaging that increases in
cytosolic Ca(2+) are not required for the upstroke of oscillations in
mitochondrial redox state, but may underlie the reoxidation process.
PMID- 17030368
TI - Carcinogenicity classification of vanadium pentoxide and inorganic vanadium
compounds, the NTP study of carcinogenicity of inhaled vanadium pentoxide, and
vanadium chemistry.
AB - It is argued that, because of inherent weaknesses in design and procedure, the
U.S. National Toxicology Program study of the carcinogenicity of inhaled vanadium
pentoxide does not provide adequate evidence to support the classification by
regulatory authorities of vanadium pentoxide as a Group 2B (possible) human
carcinogen. The extension by one regulatory authority of the carcinogenicity
classification for vanadium pentoxide to cover all vanadium compounds is also
questioned. Such an extension implies that the toxic effect of some unknown
vanadium species is more powerful than that of any oxygen species generated from
the oxygen atoms in vanadium pentoxide, and that vanadium in any form can be
converted in vivo to an undefined toxic species. There is no experimental or
theoretical basis supporting this hypothesis. For oxygen-containing compounds
like vanadium pentoxide, there is a need for some form of toxicity classification
related to their oxygen content since it is likely to be the most reactive
component of such compounds. For all particulates, such as those of crystalline
vanadium pentoxide, the special toxicity of particulates, and especially
nanoparticles, also needs separate consideration and classification.
PMID- 17030369
TI - Biomonitoring equivalents: a screening approach for interpreting biomonitoring
results from a public health risk perspective.
AB - Advances in both sensitivity and specificity of analytical chemistry have made it
possible to quantify substances in human biological specimens, such as blood,
urine, and breast milk, in specimen volumes that are practical for collection
from individuals. Research laboratories led by the Centers for Disease Control
and Prevention (CDC) in its series National Report on Human Exposure to
Environmental Chemicals [Centers for Disease Control and Prevention (CDC), 2005.
Third National Report on Human Exposure to Environmental Chemicals. NCEH Pub. No.
05-0570.] are dedicating substantial resources to designing and conducting human
biomonitoring studies and compiling biomonitoring data for the general
population. However, the ability to quantitatively interpret the results of human
biomonitoring in the context of a health risk assessment currently lags behind
the analytical chemist's ability to make such measurements. The traditional
paradigm for human health risk assessment of environmental chemicals involves
comparing estimated daily doses to health-based criteria for acceptable, safe, or
tolerable daily intakes (for example, reference doses [RfDs], tolerable daily
intakes [TDIs], or minimal risk levels [MRLs]) to assess whether estimated doses
exceed such health screening levels. However, biomonitoring efforts result in
measured chemical concentrations in biological specimens (the result of
absorption, distribution, metabolism and excretion of administered doses) rather
than estimated intake doses. Quantitative benchmarks of acceptable or safe
concentrations in biological specimens (analogous to RfDs, TDIs, or MRLs) needed
to interpret these levels exist for very few chemicals of environmental interest.
This paper discusses issues inherent in converting existing health screening
benchmarks based on intake doses to screening levels for evaluating biomonitoring
data, and presents methods and approaches that can be used to derive such
screening levels (termed "Biomonitoring Equivalents," or BEs) for a range of
chemicals and biological media.
PMID- 17030370
TI - The use of myocardial and testicular end points as a basis for estimating a
proposed tolerable daily intake for sodium monofluoroacetate (1080).
AB - This paper presents the development of a tolerable daily intake (TDI) for sodium
monofluoroacetate (1080) using the quantal myocardial and testicular toxicity end
points derived from the traditional NOAEL and newer benchmark dose (BMD) methods.
1080 is a highly toxic vertebrate pesticide that has been proven to be effective
in controlling possums and other pests. By convention, the TDIs are derived using
the traditional no-observed-adverse-effect-level (NOAEL) and applying appropriate
default uncertainty factors (UF). In addition to the default UF, a statistically
derived UF was also employed in deriving the TDI. The TDIs derived from the NOAEL
and BMD approach, 0.075 and 0.10 mg/kg bw/day, respectively, were compared. The
resulting TDI estimates using the BMDL, a statistical lower confidence bound on
the BMD, were generally consistently slightly higher than those derived using the
NOAEL approach. Based on the best fit of modelled dose-response data, a TDI of
0.03 micro g/kg bw/day is proposed for human health risk assessment of 1080.
PMID- 17030372
TI - An examination of income-related disparities in the nutritional quality of food
selections among Canadian households from 1986-2001.
AB - Socio-economic disparities in nutrition have been documented in numerous
countries, and have been linked to health inequalities. Social and economic
policy changes occurring over the last several years have resulted in growing
levels of income inequality in many countries. However, the extent to which these
temporal changes have affected nutrition disparities is largely unknown. Our
research examined income-related disparities in the nutritional quality of food
selections among Canadian households from 1986 to 2001. Data from the 1986, 1992,
1996 and 2001 Family Food Expenditure surveys were pooled together (n=35048). The
relationships between household income and the nutritional quality of food
purchases (considering nutrients both as absolute amounts and adjusted for
energy, and total energy density) were estimated using general linear models,
including tests of significance for differences across the survey years. Results
revealed significant positive relationships between income and most nutrients,
which persisted over time, and for some nutrients grew stronger. One exception
was folate, where the positive relationship between income and folate
(independent of energy) was no longer apparent in 2001; this could be attributed
to the mandatory fortification of some cereal grain products with folic acid,
which came into effect in 1998, resulting in greater availability of folate from
grain products. There was also a significant negative relationship between income
and total energy density (ratio of food energy to food weight), which persisted
across the survey years. At a time of growing income inequality and worsening
problems of poverty, food policy makers need to pay attention to the potential
for policy interventions to exacerbate or improve nutrition disparities.
PMID- 17030373
TI - Marital status, intergenerational co-residence and cardiovascular and all-cause
mortality among middle-aged and older men and women during wartime in Beirut:
gains and liabilities.
AB - Studies from the West have shown an increased risk of mortality with various
indicators of social isolation. In this study, we examine associations of marital
status and intergenerational co-residence with mortality in Lebanon, a country
that suffered wars and atrocities for almost 16 years. Using data from a
retrospective 10-year follow-up study (1984-1994) among 1567 adults aged 50 years
and older in Beirut, cardiovascular disease and all-cause mortality rates (per
1000 person-years) were computed for men and women separately. Age-adjusted
Mantel-Haenszel rate ratios (RR) and their 95% confidence intervals (CI) were
estimated, and associations were examined using multivariate Poisson regression
analysis. Most men (91.3%) were married at baseline, in contrast to only 55.4% of
women. Compared to men, women were more likely to be living in one- and three
generation households and with a married child at baseline. While widowhood was
associated with an increased risk of all-cause mortality among men only, being
never married was associated with a higher CVD mortality risk among men and
women. The presence of an adult married child was associated with a significantly
higher mortality risk for men and women, even after adjusting for household
socioeconomic indicators, marital status, lifestyle variables or pre-existing
health-related conditions (hypertension, cholesterol, and diabetes) at baseline.
The popular belief that co-residence with adult children reflects greater support
networks and an avenue for old age security may not be a valid presumption in the
Lebanese context during times of war.
PMID- 17030371
TI - Mechanisms of vasoactive intestinal peptide-elicited coronary vasodilation in the
isolated perfused rat heart.
AB - The present study investigated the potential role of vasoactive intestinal
peptide (VIP) receptors, VPAC1 and VPAC2, in VIP-elicited coronary vasodilation
of the isolated perfused rat heart. Additional studies determined the role of ATP
sensitive (K(ATP)) and voltage-gated K(+) (K(V)) channels in the VIP-elicited
coronary vasodilation. Both the selective VPAC1 agonist, K15,R16,L27VIPl-7GRF8
27, and the selective VPAC2 agonist, RO25-1553, decreased coronary vascular
resistance (CVR) in a dose-dependent manner, with EC(50) values of 1.67x10(-9)M
and 7.11x10(-9)M, respectively (VPAC1 vs VPAC2 agonist, P<0.05). K15,R16,L27VIP1
7GRF8-27 and RO25-1553 maximally reduced CVR by -42+/-4% and -39+/-6% at 1x10(-8)
and 3x10(-8)M, respectively. VIP at 1x10(-10)M decreased CVR by -14+/-2% in the
absence (vehicle), by -11+/-3% in the presence of the nonselective VIP receptor
antagonist VIP10-28 (1x10(-7)M; P>0.05 vs. vehicle) and by only -4+/-2% in the
presence of the selective VPAC2 receptor antagonist PACAP6-38 (1x10(-7)M; P<0.05
vs. vehicle). In additional studies, VIP at 1x10(-10)M decreased CVR by -22+/-1%
in the absence (control) and by only -10+/-2% in the presence of the nonselective
K(+) channel blocker tetrabutylammonium (3x10(-4)M; P<0.05 vs. control). VIP
reduced CVR by -4+/-1% in the presence of the K(ATP) channel blocker
glibenclamide (3x10(-6)M; P<0.05 vs control) and by -28+/-2% in the presence of
the K(V) channel blocker 4-aminopyridine (3x10(-4)M; P>0.05 vs control). Thus,
selective VPAC1 and VPAC2 receptor activation in the coronary circulation
produces vasodilation and the VIP-elicited coronary vasodilation involves
activation of VPAC2 receptors and K(ATP) but not K(V) channels. In addition,
VIP10-28 does not effectively block coronary vascular VIP receptors.
PMID- 17030374
TI - The suppressor of cytokine signalling-1 (SOCS-1) gene is overexpressed in
Philadelphia chromosome negative chronic myeloproliferative disorders.
AB - The suppressor of cytokine signalling-1 (SOCS-1) is a negative regulator of
signal transduction mediated by cytoplasmic tyrosine kinases such as the Janus
kinases (JAKs). We investigated SOCS-1 expression in bone marrow cells from
Philadelphia chromosome negative chronic myeloproliferative disorders (Ph(-)
CMPD) and normal haematopoiesis (n=121), and additionally in peripheral blood
samples (n=18). Except for chronic idiopathic myelofibrosis harbouring wild-type
JAK2, other Ph(-) CMPD expressed significantly higher SOCS-1 levels of up to 14
fold compared to the control group (p<0.001) independent of the JAK2 status. The
mononuclear cell fraction but not granulocytes in patients with Polycythaemia
vera also significantly overexpressed SOCS-1. We conclude that up-regulation of
the SOCS-1 gene might reflect a compensatory feedback mechanism with different
emphasis among Ph(-) CMPD subtypes independent of an underlying JAK2 (V617F)
mutation.
PMID- 17030375
TI - Possible antipsychotic effects of minocycline in patients with schizophrenia.
AB - We present two cases of patients with schizophrenia treated with minocycline.
Minocycline (a second-generation tetracycline) is an established and safe broad
spectrum antibiotic that crosses the blood-brain barrier, with additional
efficacy for diseases such as acne and rheumatoid arthritis. Animal studies have
suggested that minocycline may prevent progression of some neurological
disorders. Moreover, it has been reported that minocycline might have
antidepressant effects. We report two cases of acute schizophrenia with
predominant catatonic symptoms that responded to minocycline.
PMID- 17030376
TI - Decreased serum levels of transforming growth factor-beta1 in patients with
autism.
AB - BACKGROUND: The neurobiological basis for autism remains poorly understood. Given
the key role of transforming growth factor-beta1 (TGF-beta1) in brain
development, we hypothesized that TGF-beta1 plays a role in the pathophysiology
of autism. In this study, we studied whether serum levels of TGF-beta1 are
altered in patients with autism. METHODS: We measured serum levels of TGF-beta1
in 19 male adult patients with autism and 21 age-matched male healthy subjects
using enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum levels
(7.34+/-5.21 ng/mL (mean+/-S.D.)) of TGF-beta1 in the patients with autism were
significantly (z=-5.106, p<0.001) lower than those (14.48+/-1.64 ng/mL (mean+/
S.D.)) of normal controls. However, there were no marked or significant
correlations between serum TGF-beta1 levels and other clinical variables,
including Autism Diagnostic Interview-Revised (ADI-R) scores, Yale-Brown
Obsessive-Compulsive Scale (Y-BOCS), aggression, Theory of Mind, and Intellectual
Quotient (IQ) in patients. CONCLUSIONS: These findings suggest that decreased
levels of TGF-beta1 may be implicated in the pathophysiology of autism.
PMID- 17030377
TI - Characterization of the mobilization determinants of pAN12, a small replicon from
Rhodococcus erythropolis AN12.
AB - Bacteria belonging to the Gram-positive actinomycete species, Rhodococcus
erythropolis, are diverse not only in terms of metabolic potentials but the
plasmids they encode. It was shown previously that the R. erythropolis AN12
genome harbors a 6.3kb cryptic plasmid called pAN12, which is a member of the
pIJ101 family of plasmids. Here we show that pAN12 is conjugatively mobilizable
into other rhodococcal strains. A series of plasmid deletion constructs were
tested for loss of mobility to identify the pAN12 cis-acting conjugation
requirement. In this way, an approximately 700bp region was found to be required
for plasmid transmission. A small 61bp element within this region confers
mobility to an otherwise non-mobilizable plasmid. Unlike pIJ101, which encodes
all necessary factors for transfer, pAN12 mobility is dependent on the presence
of an AN12 megaplasmid, pREA400.
PMID- 17030380
TI - Hydroquinone: acute and subchronic toxicity studies with emphasis on
neurobehavioral and nephrotoxic effects.
AB - Hydroquinone (HQ) is a common water-soluble constituent of foods, an ingredient
in skin lightening preparations, a photographic developer, and an antioxidant
used in the preparation of industrial polymers. In this series of studies,
aqueous solutions of HQ were given by gavage to male and female Sprague-Dawley
rats to determine the acutely lethal dose, the clinical signs of behavioral
toxicity associated with doses at or near a dose causing mortality, and the
effects of the administration of dose levels resulting in acutely observable
behavioral effects when administered 5 days/week for 13 weeks. The acute dermal
toxicity of HQ in rabbits was also determined. For the acute oral toxicity study,
groups of five male and five female rats were administered single oral doses of
375, 345, 315, or 285 mg/kg. At all dose levels, animals exhibited minor to
moderate tremors and minor convulsions within the first hour after dosing. The
acute oral LD50 value for both sexes combined was >375 mg/kg. Dermal application
of 2000 mg/kg HQ to rabbits under an occlusive wrap for 24 h did not result in
neurobehavioral effects or mortality. Subchronic exposure was accomplished by
administration of doses of 200, 64, 20, or 0 mg/kg/day of HQ in water to groups
of male and female rats study (10/sex/group). A functional observational battery
(FOB) was used to detect neurobehavioral effects prior to HQ exposure and
postexposure at 1, 6, and 24 h and 7, 14, 30, 60, and 91 days. Daily clinical
observations were also recorded for each animal. Doses of 200 or 64 mg/kg HQ
resulted in acutely observable behavioral effects including tremors and reduced
activity. Tremors occurred within one hour of dosing and resolved by the 6-h
examination. Brain weights were not altered by HQ administration, but mean
terminal body weight was reduced approximately 7% for the 200 mg/kg males.
Neuropathologic examination of the CNS and PNS, including special stains for
myelin and axonal process, did not reveal any morphologic lesions associated with
HQ administration or secondary to repetitive CNS stimulation by HQ. The
nephrotoxic effects observed in Fischer 344 rats after HQ exposure was not
observed in this study with Sprague-Dawley rats. Oral doses of >or=64/mg/kg HQ
resulted in acute neurobehavioral effects indicative of CNS stimulation; however,
subchronic exposure to dose levels that produced repetitive CNS stimulation by HQ
did not result in an exacerbation of acute stimulatory effects over time or
morphologic changes in the CNS or PNS or nephrotoxicity.
PMID- 17030379
TI - Transdermal absorption of the herbicide 2,4-dichlorophenoxyacetic acid is
enhanced by both ethanol consumption and sunscreen application.
AB - Xenobiotics absorption is a health concern and skin is a major exposure site for
many of these chemicals. Both alcohol consumption and topical sunscreen
application act as transdermal penetration enhancers for model xenobiotics. The
effect of combining these two treatments on transdermal absorption of the
herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was therefore examined. Skin
from rats ingesting low (1.5 g/kg) medium (4.3 g/kg) or high (6 g/kg) ethanol
doses or saline control was treated with a commercially available sunscreen
containing titanium dioxide and octyl methoxycinnimate and transdermal absorption
of 2,4-D was monitored. Ethanol increased penetration by a factor of 1.9, 2.0 and
2.5 for animals treated with 1.5, 4.3 and 6 g/kg respectively, demonstrating an
ethanol-induced dose response. Sunscreen application to skin from ethanol gavaged
rats caused 2,4-D absorption above that induced by ethanol alone by an additional
factor of 1.3, 2.1 and 2.9 for 1.5, 4.3 and 6 g/kg respectively. Comparing 2,4-D
transdermal absorption after exposure to both ethanol and sunscreen with a
theoretical value (sum of penetration after ethanol or sunscreen treatment)
demonstrates that these two treatments enhance additively at the higher doses
tested. Results of this study emphasize the importance of limiting excessive
alcohol consumption in individuals with potential herbicide exposure rather than
discouraging the use of sunscreens, since the consequences of UV-induced skin
cancer are far more series than the risks that would be associated with observed
increases in chemical exposure.
PMID- 17030378
TI - Supernatant of bacterial fermented soybean induces apoptosis of human
hepatocellular carcinoma Hep 3B cells via activation of caspase 8 and
mitochondria.
AB - SC-1, the aqueous phase of soybean fermentation products by bacteria (Bacillus
subtilis and Bacillus brevis), significantly inhibited the growth and
clonogenesity of human hepatocellular (Hep 3B), mouse hepatocellular (ML-1), and
human colorectal (HCT 116 and HT-29) carcinoma cells. Cytotoxicity of SC-1 in Hep
3B cells was through the process of apoptosis characterizing by increase in cell
population of sub-G(1) phase, fragmentation of DNA, and change of nuclear
morphology. Treatment of Hep 3B cells with SC-1 activated caspase 8 and caspase
3. Elevation of nuclear DNA fragmentation factor 40 (DFF40) and cleavage form of
poly(ADP-ribose) polymerase (PARP) were also observed. SC-1 also activated
intrinsic pathway via increase of pro-apoptotic (tBid, Bak and Bax) and decrease
of anti-apoptotic (Bcl-2 and Bcl-x(L)) proteins on mitochondria, disruption of
mitochondrial membrane potential, release of cytochrome c and Smac (second
mitochondria-derived activator of caspase/direct IAP binding protein with low PI)
from mitochondria, and activation of caspase 9. Inhibition on protein expression
of Ku70 in cytosol and cyclooxygenase (COX)-2, but not COX-1, in whole cell
lystes were revealed in SC-1-treated Hep 3B cells. These results suggest caspase
8, Ku70 and mitochondria are involved in the antitumor mechanism of SC-1 in Hep
3B cells.
PMID- 17030381
TI - Protective effect of Ugni molinae Turcz against oxidative damage of human
erythrocytes.
AB - Ugni molinae Turcz, also known as "Murtilla", is a plant that grows in the south
of Chile. Infusions of its leaves have long been used in traditional native
herbal medicine. The chemical composition of the leaves indicates the presence of
polyphenols, which have antioxidant properties. In the present work, the
antioxidant properties of U. molinae were evaluated in human erythrocytes exposed
in vitro to oxidative stress induced by HClO. The experiments were carried out by
scanning electron microscopy (SEM) and hemolysis measurements. The SEM
observations showed that HClO induced a morphological alteration in the red blood
cells from a discoid to an echinocytic form. According to the bilayer couple
hypothesis, the formation of echinocytes indicates that HClO was inserted in the
outer leaflet of the erythrocyte membrane. However, a concentration as low as 10
microM gallic acid equivalents (GAE) U. molinae aqueous extract neutralized the
shape change effect of HClO applied in a concentration as high as 0.25 mM. The
significant protection of U. molinae aqueous extract was also shown in the
hemolysis experiments. In fact, very low concentrations of the extract
considerably reduced the deleterious capacity of HClO to induce hemolysis in red
blood cells. It is concluded that the location of the extract components into the
membrane bilayer and the resulting restriction on its fluidity might hinder the
diffusion of HClO and its consequent damaging effects. This conclusion can also
imply that this restriction could apply to the diffusion of free radicals into
cell membranes and the subsequent decrease of the kinetics of free radical
reactions.
PMID- 17030382
TI - Acute and subchronic oral toxicity studies in rats of a hydrolyzed chicken
sternal cartilage preparation.
AB - Two acute and subchronic oral toxicity studies were conducted in rats to evaluate
safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell
Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic
acid. In the acute oral toxicity study, five males and five females of Sprague
Dawley rats were administered a single dose of 5000 mg of the test product per kg
body weight and observed for 14 days. All animals survived and exhibited normal
body weight gain throughout the study. Macroscopic necropsy examination conducted
on day 15 revealed no gross pathological lesions in any of the animals. In the
subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into
four same-sex groups (10 animals/group). Animals in each group were administered
daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for
over 90 days. All animals survived and showed no significant changes in their
body weights and histopathology. Although some differences were observed between
the treated and control animals in several parameters, they were generally not
dose-related or considered to be of toxicological significance. In conclusion,
the results from the two oral toxicity studies with male and female young adult
rats indicated that the test preparation from hydrolyzed chicken sternal
cartilage collagen (BioCell Collagen II) was well tolerated at all four doses
tested.
PMID- 17030383
TI - Occupational exposure of hairdressers to [14C]-para-phenylenediamine-containing
oxidative hair dyes: a mass balance study.
AB - We monitored the exposure of hairdressers to oxidative hair dyes for 6 working
days under controlled conditions. Eighteen professional hairdressers (3/day)
coloured hairdresser's training heads bearing natural human hair (hair length:
approximately 30 cm) for 6 h/working day with a dark-shade oxidative hair dye
containing 2% [14C]-para-phenylenediamine (PPD). Three separate phases of hair
dyeing were monitored: (A) dye preparation/hair dyeing, (B)
rinsing/shampooing/conditioning and (C) cutting/drying/styling. Ambient air and
personal monitoring samples (vapours and particles), nasal and hand rinses were
collected during all study phases. Urine (pre-exposure, quantitative samples for
the 0-12, 12-24, 24-48 h periods after start of exposure) and blood samples
(blank, 4, 8 or 24 h) were collected from all exposed subjects. Radioactivity was
determined in all biological samples and study materials, tools and washing
liquids, and a [14C]-mass balance was performed daily. No adverse events were
noted during the study. Waste, equipment, gloves and coveralls contained 0.41+/
0.16%, dye mixing bowls 2.88+/-0.54%, hair wash 45.47+/-2.95%, hair+scalp 53.46+/
4.06% of the applied radioactivity, respectively. Plasma levels were below the
limit of quantification (10 ng PPDeq/mL). Total urinary 0-48 h excretion of [14C]
levels ranged from a total of <2-18 microg PPDeq and was similar in subjects
exposed during the different phases of hair dyeing. Minimal air levels at or
slightly above the limit of quantification were found in a few personal air
monitoring samples during the phases of hair dyeing and hair cutting, but not
during the rinsing phase. Air area monitoring samples or nasal rinses contained
no measurable radioactivity. Hand residues ranged from 0.006 to 0.15 microg
PPDeq/cm2, and were found predominantly after the cutting/drying phase. The mean
mass balance of [14C] across the six study days was 102.50+/-2.20%. Overall, the
mean, total systemic exposure of hairdressers to oxidative hair dyes during a
working day including 6 hair dyeing processes was estimated to be <0.36 microg
PPDeq/kg body weight/working day. Our results suggest that (a) current safety
precautions for the handling of hair dyes offer sufficient protection against
local and systemic exposure and (b) professional exposure to oxidative hair dyes
does not pose a risk to human health.
PMID- 17030384
TI - Influence of colostrum treated by heat on immunity function in goat kids.
AB - The aim was to evaluate the influence of goat colostrum treated by heat on immune
function in kids. Thirteen newborn kids were fed untreated colostrum (group A)
and 13 kids were fed colostrum treated by heat (56 degrees C, 30 min) (group B).
Blood samples were obtained at eight time points between the ages of 0 h to 28
days. Serum protein fractions, IgG levels and phagocytic activity of neutrophils
were determined. A delayed type hypersensitivity (DTH) test was used, clinical
status and body weight was recorded. There were no clinical signs of disease and
no differences (P>0.05) on body weight between groups were noted. Kids from group
B had less total protein levels and gamma-globulins than kids from group A
(P<0.05). A decrease in serum IgG levels (P<0.05) was observed in kids from group
B during all experiment. DTH response in kids from group B was lower (P<0.01)
than group A, suggesting alteration on cellular immune system. No effects on
phagocytic activity of the neutrophils were observed when both groups were
compared (P>0.05). These results showed that colostrum treated by heat impaired
some immunological parameters in kids, but these changes did not affect on
clinical status or performance.
PMID- 17030385
TI - Cleaved inflammatory lactoferrin peptides in parotid saliva of periodontitis
patients.
AB - Lactoferrin (Lf) is a member of the transferrin family of iron-binding anti
bacterial proteins, present in most exocrine secretions, such as saliva, and
plays an important role in mucosal defense. In this study, we identified small Lf
peptides with Con A low-affinity in the parotid saliva of chronic periodontitis
patients by Con A two-dimensional immunoelectrophoresis, Con A affinity
chromatography and Western blotting using anti-human Lf polyclonal Ab. N-terminal
amino acid sequencing of the four Con A low-affinity Lf peptides confirmed them
to be fragments of intact Lf. The detection ratio of the proteinase 3 (PR3)-like
activity was elevated in the parotid saliva of periodontitis patients and was
associated with the severity of clinical symptoms. PR3 protein was also detected
in the parotid saliva of periodontitis patients, and PR3, but not human leukocyte
elastase and cathepsin G, degraded intact Lf. Con A low-affinity saliva Lf
peptides showed no anti-bacterial activity against Escherichia coli, and had a
reduced iron-chelating capacity. Con A low-affinity saliva Lf peptides, PR3
treated Lf preparation and two of four synthetic polypeptides induced the
production of interleukin IL-6, monocyte chemoattractant protein-1 and IL-8, and
the activation of NF-kappaB in human oral epithelial HSC-2 cells. Furthermore,
concentrations of the Lf peptides in the parotid saliva of periodontitis patients
were increased with a correlation to the severity of clinical symptoms. These
results suggest that Lf in the parotid saliva of periodontitis patients was
degraded into small peptides by the PR3-like activity with the capability to
induce inflammatory mediators.
PMID- 17030386
TI - [Diagnosis and management of cervicofacial congenital teratomas: about 4 cases,
literature review and restatement].
AB - Cervicofacial teratomas are rare developmental lesions, more often benign in
their histology. They can lead to respiratory distress and death caused by airway
obstruction at birth. Prenatal diagnosis raises on ultrasound examination
precising locoregional consequences of the tumor and surgical possibilities. In
the propitious cases, prenatal MRI examination is useful to precise tumor's
limits and cerebral status of the foetus. At birth, coordinate management
involving anaesthetists, paediatricians and specialized surgeons decrease
morbidity and mortality. Complete early surgical excision must be managed as soon
as possible and planned thanks to TDM end MRI examination.
PMID- 17030387
TI - [Efficiency of the combination of Mersilene-musculocutaneous flap in the
reconstruction of full-thickness chest wall defects. A retrospective study of 14
cases].
AB - SUBJECT: The tumors of chest wall can be responsible of large full-thickness
defects. The skeletal stabilization by different synthetic materials with
numerous modalities of use and the superficial coverage of the defect by a
musculocutaneous flap are the two imperatives parts of this reconstruction.
PATIENTS AND METHODS: From January 1997 to January 2006, 14 patients, 10 males
and 4 females, aged between 17 and 63 years old and suffering from full-thickness
chest wall defects secondary to tumor resection have benefited from a simple
reconstruction, wherever the defect, by a Mersilene Mesh and a muscular or
musculocutaneous flap. These defects measured between 8 x 12 cm and 14 x 16 cm
and were located in the anterior part of the chest in 3 cases, with resection of
the upper half of the sternum and the internal part of both clavicles and the
first three ribs, and in the lateral part of the chest in 11 cases with resection
between 3 and 5 ribs. The histological diagnoses of these tumors were 3
chondrosarcomas, 3 sternum and 1 rib metastases, 2 desmoid tumors, 1 Ewing's
sarcoma, 4 benign tumors. The flaps used were pedicled in 13 cases and based on
the latissimus dorsi muscle, the serratus muscle and the pectoralis major muscle;
in 1 case, the latissimus dorsi musculocutaneous flap was free. RESULTS: The
skeletal stabilisation seems satisfying. There was no problems with the pulmonary
function except in 4 cases where a dyspnea appears in sustained effort. No
vascular complication on these flaps was noted. With a mean follow up of 46
months, there was no local recurrence of the malignant tumors. Two patients were
deceased 1 year after surgery.0. CONCLUSION: The Mersilene mesh associated with a
locoregional musculocutaneous flap represent a simple and efficient solution for
the treatment of such defects.
PMID- 17030388
TI - [Pilomatricoma or calcifying epithelioma of Malherbe. A pediatric review of 89
cases].
AB - The authors report an exclusive pediatric review of 89 pilomatricomas operated in
83 patients. This tumor, also known as calcifying epithelioma of Malherbe, is
common in the pediatric population and occurs mainly on the head and neck region.
It is a benign skin neoplasm usually misdiagnosed and yet the most common hair
follicle tumor. The treatment is a surgical excision taking the overlying skin.
Principal characteristics and clinical presentation of this tumor are discussed.
PMID- 17030389
TI - [Salvage of a leg avulsion injury by vacuum negative pressure therapy: a case
report].
AB - We present the case of a 51-year-old woman who suffered an avulsion injury of the
right leg in a car accident. In a first time, the simple suture with tiny
debridement of the flaps is a failure and lead to a nearly complete necrosis. In
a second time, a total avulsion of the devitalized skin is realised and a
circumferential VAC system is placed on the wound. Four cycles of vacuum therapy
and twelve days later, a split-thickness skin mesh-graft is applied on the leg.
This one has a very good take and allows the patient to stand up one month after
the initial accident. This example underlines the role of cleaning and pro
budding of the negative therapy after the salvage of a leg avulsion.
PMID- 17030390
TI - [Amelanotic malignant melanoma: about three cases].
AB - The amelanotic melanoma is a rare type of malignant melanoma. The purpose of this
report is to point out this aspect of melanoma, whose diagnostic delay is
frequent. We describe one localisation on the penis, rare in this kind of
melanoma and two cases of the extremities, more frequent localization of the
amelanotic melanoma. The therapeutic issues and recommendation are similar to the
classical pigmented malignant melanoma.
PMID- 17030391
TI - [Hereditary neuropathy with liability to pressure palsies (HNPP) in hand surgery:
reminds and warn against a usually unrecognised disease].
AB - Tomacula is a rare hereditary disease due to a deletion on chromosome 17.
Clinical presentation varies but patients usually complain of recurrent
paraesthesiaes and palsies related to compression or trauma of a peripheral
nerve. Diagnosis is based on electrophysiological studies, nerve biopsies and
genetic tests. Implications for the patient and family members are a genetic
counselling and some simple preventive measures. Although there is no curative
treatment for this neuropathy, surgery can be useful for decompression of nerves
and neurolysis. However, the surgical act increases the risk of nerve damage.
Knowing about the diagnosis can help the patient and the surgical team avoid
causing lesions.
PMID- 17030392
TI - Vanadium distribution, lipid peroxidation and oxidative stress markers upon
decavanadate in vivo administration.
AB - The contribution of decameric vanadate species to vanadate toxic effects in
cardiac muscle was studied following an intravenous administration of a
decavanadate solution (1mM total vanadium) in Sparus aurata. Although decameric
vanadate is unstable in the assay medium, it decomposes with a half-life time of
16 allowing studying its effects not only in vitro but also in vivo. After 1, 6
and 12h upon decavanadate administration the increase of vanadium in blood
plasma, red blood cells and in cardiac mitochondria and cytosol is not affected
in comparison to the administration of a metavanadate solution containing labile
oxovanadates. Cardiac tissue lipid peroxidation increases up to 20%, 1, 6 and 12h
after metavanadate administration, whilst for decavanadate no effects were
observed except 1h after treatment (+20%). Metavanadate administration clearly
differs from decavanadate by enhancing, 12h after exposure, mitochondrial
superoxide dismutase (SOD) activity (+115%) and not affecting catalase (CAT)
activity whereas decavanadate increases SOD activity by 20% and decreases (-55%)
mitochondrial CAT activity. At early times of exposure, 1 and 6h, the only effect
observed upon decavanadate administration was the increase by 20% of SOD
activity. In conclusion, decavanadate has a different response pattern of lipid
peroxidation and oxidative stress markers, in spite of the same vanadium
distribution in cardiac cells observed after decavanadate and metavanadate
administration. It is suggested that once formed decameric vanadate species has a
different reactivity than vanadate, thus, pointing out that the differential
contribution of vanadium oligomers should be taken into account to rationalize in
vivo vanadate toxicity.
PMID- 17030393
TI - Novel anticonvulsant drugs.
AB - Principles of complex mechanisms of action of anticonvulsants including latest
reports concerning new antiepileptic drugs (AED) are considered. Different
aspects of new anticonvulsant drugs (2nd generation) from preclinical and
clinical testing, pharmacokinetics, and mono or combination therapy in children
and adults are summarized. In the following condensed synopsis pharmacological
and clinical characteristics of gabapentin (GBP), lamotrigine (LTG),
levetiracetam (LEV), oxcarbazepine (OXC), pregabalin (PGB) and tiagabine (TGB) as
well as topiramate (TPM) and zonisamide (ZNS) are discussed. In addition to the
mechanisms of action, pharmacokinetics, interactions, indications and dosages as
well as side effects are considered. Important data concerning the effect and
tolerability of anticonvulsant drugs can be obtained from controlled studies. In
comparison to drugs of the first generation (phenobarbital [PB], primidon [PRD],
phenytoin [PHT], carbamazepine [CBZ] and valproic acid [VPA]) the potential for
interactions and side effects due to enzyme induction or inhibition is reduced by
most of the anticonvulsant drugs of the second generation. New anticonvulsant
drugs increase the spectrum of treatment and represent further steps with regard
to the optimization of an individual therapy of the epilepsies.
PMID- 17030394
TI - Anaesthesia in patients suffering from organophosphorus intoxication-
interactions between general anaesthetics and acetylcholine in cortical networks
in vitro.
AB - In scenarios of mass destruction it is likely that victims are intoxicated by
organophosphates and, at the same time, physically injured. Organophosphate
compounds produce excessive cholinergic overstimulation in the CNS via blocking
acetylcholinesterase activity. The specifics of acute care and anaesthesia in
physically traumatized and intoxicated patients are largely unknown. Recent
studies in animals and human subjects demonstrated that acetylcholinesterase
inhibitors reverse anaesthesia. Two distinct mechanisms are potentially involved.
First, acetylcholine produces an excitatory drive onto neurons, thereby
counterbalancing the inhibitory actions of anaesthetics. Anaesthesia is reversed
because it critically depends on a distinctive depression of several central
nervous functions. Second, cholinergic stimulation may affect the mechanisms by
which anaesthetics mediate their depressant actions on central neurons. In this
case acetylcholine reverses anaesthesia by decreasing the potency of anaesthetic
agents. In order to identify potential mechanisms involved in cholinergic
reversal of anaesthesia we have investigated interactions between acetylcholine
and the volatile anaesthetic sevoflurane in isolated cortical brain slices. Our
results provide evidence that cholinergic stimulation counterbalances the effects
of general anaesthetics by increasing neuronal excitability, and, in addition, by
decreasing anaesthetic potency. These findings imply that in patients suffering
from organophosphorus intoxication dose requirements for general anaesthetics are
considerably increased.
PMID- 17030395
TI - Effect of composite shade, increment thickness and curing light on temperature
rise during photocuring.
AB - OBJECTIVES: To examine the effect of composite shade, increment thickness and
curing light characteristics on the temperature rise associated with composite
photocuring. METHODS: Four shades (C2, A4, B1 and B3), four sample thicknesses
(2, 3, 4 and 5 mm) of a hybrid resin composite and two curing units, one with two
modes of curing, were investigated. The composite samples were packed in
polytetrafluoroethylene (PTFE) moulds and cured for 40 s. Samples cured with the
ramp curing mode were irradiated for only 20 s. Temperature rises on the
undersurface of the curing resin composite were measured using an infrared
scanning system. RESULTS: Shade C2 produced the highest maximum temperature of
all shades (56.7 degrees C). Thinner samples produced greater temperature rises
(2mm induced 60.9 degrees C, 5 mm induced 45.7 degrees C). Samples cured with
Optilux 501 unit produced greater temperature rises (60.9 degrees C) than those
cured with Dentsply unit (56.2 degrees C). CONCLUSIONS: There was a quantifiable
amount of heat generated during visible light curing of resin composite. The
amount of heat generated was influenced by shade selected, thickness of material
and characteristics of the light curing unit.
PMID- 17030396
TI - Assessment of the safety of two ozone delivery devices.
AB - OBJECTIVES: To evaluate the safety of an ozone gas device designed for use in
dentistry. METHODS: Two commercially available ozone applicators, Ozi-cure and
HealOzone were used in a clinical simulation using a phantom head while
recordings of ozone levels were made in pharyngeal and nasal regions of the
patient and near the mouth of the operator. Clinical simulations included ozone
application for caries management and endodontic treatment. Recordings were made
five times with different levels of suction to assess the effect on ozone levels.
RESULTS: The results with Ozi-cure on caries mode resulted in a peak ozone level
in the pharynx of 1.33+/-0.52 ppm when no suction was used. The use of suction
nearby reduced the ozone level to zero while suction on the opposite side of the
mouth reduced the level to 0.22+/-0.04 ppm. Used on endodontic mode the peak
ozone level in the pharynx was 5.51+/-1.63 ppm when no suction was used. The use
of suction nearby reduced the ozone level to zero while suction on the opposite
side of the mouth reduced the level to 0.84+/-0.54 ppm. Recordings in the
patient's nasal region gave a peak of 0.22 ppm when using the Ozi-cure on
endodontic mode with no suction. At the operator's mouth the ozone level did not
exceed 0.01 ppm although the characteristic smell of ozone was detectable. All
recordings with HealOzone were zero. Concentrations of 15 ppm were recorded in a
simulated tooth cavity with Ozi-cure and >20 ppm with HealOzone. CONCLUSIONS: The
Ozi-cure device when used without adequate suction allows ozone to be reach a
concentration above permitted levels and therefore should not be used. The
HealOzone was safe to use.
PMID- 17030397
TI - A simple and accurate method for quantification of magnetosomes in magnetotactic
bacteria by common spectrophotometer.
AB - A simple apparatus for measuring the magnetism of magnetotactic bacteria was
developed with a common laboratory spectrophotometer, which was based on
measuring the change in light scattering resulting from cell alignment in a
magnetic field. A multiple coils were built around the cuvette holder of the
spectrophotometer to compensate geomagnetic field and to generate two mutually
perpendicular magnetic fields. In addition, we defined a novel magnetism
parameter, R(mag), by modifying the definition of C(mag) to a normalized
parameter with the culture absorbance obtained without application of magnetic
field. The number of magnetosomes in each cell was determined by transmission
electron microscopy to assess the relationship between the two magnetism
parameters and the distribution of magnetosomes in the cells. We found that both
R(mag) and C(mag) were linearly correlated rather with the percentage of
magnetosome-containing bacteria than with the average magnetosome numbers, and
R(mag) exhibited a better linearity than C(mag) with respect to the percentage of
magnetosome-containing bacteria.
PMID- 17030398
TI - Antisociality, underarousal and the validity of the Concealed Information
Polygraph Test.
AB - The Concealed Information Polygraph Test has been advocated as the preferred
method for the physiological detection of deception. In this study, we further
examined the validity of the Concealed Information Test in antisocial
individuals. Physiological responding to concealed information was assessed in 48
male prisoners, and compared with responding in 31 male community volunteers.
Based upon the association between antisociality and autonomic hyporesponsivity,
lower detection rates were expected in the prisoners. Participants were
questioned on five personally significant items (e.g., day of birth), instructed
to deny recognition of this information, and promised a financial reward when
able to hide recognition. Prisoners showed reduced autonomic reactivity in
comparison to the community volunteers. This hyporesponsivity had little impact
on the sensitivity of the Concealed Information Test. Detection efficiency in the
prisoners was significantly above chance (d=2.67; a=0.82; 79%), and did not
differ significantly from that obtained in the community volunteers (d=3.04;
a=0.85; 87%). The present data support the validity of the Concealed Information
Test in criminal populations.
PMID- 17030399
TI - The effects of social stress and cortisol responses on the preconscious selective
attention to social threat.
AB - The purpose of the present study was to investigate the effects of social stress
and stress-induced cortisol on the preconscious selective attention to social
threat. Twenty healthy participants were administered a masked emotional Stroop
task (comparing color-naming latencies for angry, neutral and happy faces) in
conditions of rest and social stress. Stress was induced by means of the Trier
social stress test. Based on the stress-induced increase in cortisol levels,
participants were allocated post hoc (median-split) to a high and low responders
group. In contrast to low responders, high responders showed a negative or
avoidant attentional bias to threat (i.e. shorter latencies for angry than
neutral faces) in the rest condition. Most importantly, although low responders
became avoidant, the high responders became vigilant to the angry faces after
stress induction. There were no such effects for happy faces. Our findings are in
line with previous studies in both animals and humans, that associate high
glucocorticoid stress-responsiveness with diminished avoidance and prolonged
freezing reactions during stress.
PMID- 17030400
TI - Detection and visualization of storm hydrograph changes under urbanization: an
impulse response approach.
AB - Urbanization often alters catchment storm responses, with a broad range of
potentially significant environmental and engineering consequences. At a
practical, site-specific management level, efficient and effective assessment and
control of such downstream impacts requires a technical capability to rapidly
identify development-induced storm hydrograph changes. The method should also
speak specifically to alteration of internal watershed dynamics, require few
resources to implement, and provide results that are intuitively accessible to
all watershed stakeholders. In this short paper, we propose a potential method
which might satisfy these criteria. Our emphasis lies upon the integration of
existing concepts to provide tools for pragmatic, relatively low-cost
environmental monitoring and management. The procedure involves calibration of
rainfall-runoff time-series models in each of several successive time windows,
which sample varying degrees of watershed urbanization. As implemented here, only
precipitation and stream discharge or stage data are required. The readily
generated unit impulse response functions of these time-series models might then
provide a mathematically formal, yet visually based and intuitive, representation
of changes in watershed storm response. Nominally, the empirical response
functions capture such changes as soon as they occur, and the assessments of
storm hydrograph alteration are independent of variability in meteorological
forcing. We provide a preliminary example of how the technique may be applied
using a low-order linear ARX model. The technique may offer a fresh perspective
on such watershed management issues, and potentially also several advantages over
existing approaches. Substantial further testing is required before attempting to
apply the concept as a practical environmental management technique; some
possible directions for additional work are suggested.
PMID- 17030401
TI - Estimation of terrestrial chemical spill risk factors using a modified Delphi
approach.
AB - The large number of chemical spills each year in the United States presents a
potentially significant risk to human health and the environment. In an effort to
manage this risk, the authors are developing a screening tool to assess the
immediate threat to human and environmental receptors from land-based chemical
spills. As part of this development effort, a modified Delphi survey was employed
to determine the most important factors governing this risk and the relative
importance of these factors. Results of the survey indicate that accounting for
the attributes of the spilled chemical as well as the characteristics of the
surrounding environment is imperative in making informed decisions regarding
spill planning and mitigation. Survey results further indicate the greatest
concern during spill events to be the risk to human health, which must be
considered directly as well as factored into decisions concerning the protection
of environmental receptors.
PMID- 17030402
TI - The effect of landfill leachate composition on organics and nitrogen removal in
an activated sludge system with bentonite additive.
AB - A pre-denitrification activated sludge system (AS) without internal recycle was
used in lab-scale studies of landfill leachate treatment. A bentonite supplement
at a ratio of 1:4 (mineral : biomass) was used to ensure high sludge settling
levels and to serve as a micro-organisms carrier. The system was operated within
different parameters such as hydraulic retention time (HRT), ammonia loading rate
(ALR) or external recycle ratio, which was adapted to treat varying leachate
concentrations of COD and ammonia, ranging from 1020 to 2680 mgO(2)l(-1) and 400
890 mgNH(4)-Nl(-1) respectively. The nitrification was complete and ammonia
oxidation reached 99%; this was obtained while the ALR did not exceed 0.09 g
NH(4)(+)-Ng(-1)MLVSS d(-1) and HRT was not lower than 1 day (in the aeration
reactor). The performance of denitrification was successfully improved by
controlling the external recycle rate, when the BOD(5)/N ratio in the raw
leachate was 4.1. Consequently, N-removal of up to 80% was achieved. A 10-fold
decrease in the denitrification rate was obtained at a BOD(5)/N ratio of 0.5. The
efficiency of COD removal varied significantly from 36% to 84%. The positive
effect of bentonite addition was determined and is discussed based on preliminary
studies. The experiments were carried out in fill-and-draw activated sludge with
bentonite; the biomass ratio was 1:2. The activated sludge with bentonite was fed
with a synthetic high ammonia and organic-free medium.
PMID- 17030403
TI - The effect of model structure and data in modeling land conditions in disturbed
complex ecosystems.
AB - Off-road vehicles increase soil erosion by reducing vegetation cover and other
types of ground cover, and by changing the structure of soil. The investigation
of the relationship between disturbance from off-road vehicles and the intensity
of the activities that involve use of vehicles is essential for water and soil
conservation and facility management. Models have been developed in a previous
study to predict disturbance caused by off-road vehicles. However, the effect of
data on model quality and model performance, and the appropriate structure of
models have not been previously investigated. In order to improve the quality and
performance of disturbance models, this study was designed to investigate the
effects of model structure and data. The experiment considered and tested: (1)
two measures of disturbance based on the Vegetation Cover Factor (C Factor) of
the Revised Universal Soil Loss Equation (RUSLE) and Disturbance Intensity; (2)
model structure using two modeling approaches; and (3) three subsets of data. The
adjusted R-square and residuals from validation data are used to represent model
quality and performance, respectively. Analysis of variance (ANOVA) is used to
identify factors which have significant effects on model quality and performance.
The results of the ANOVA show that subsets of data have significant effects on
both model quality and performance for both measures of disturbance. The ANOVA
also detected that the C Factor models have higher quality and performance than
the Disturbance models. Although modeling approaches are not a significant factor
based on the ANOVA tests, models containing interaction terms can increase the
adjusted R-squares for nearly all tested conditions and the maximum improvement
can reach 31%.
PMID- 17030404
TI - Analysis of livelihood security: a case study in the Kali-Khola watershed of
Nepal.
AB - This paper examines household livelihoods in highland and lowland communities of
the Kali-Khola agricultural watershed in western Nepal on the basis of economic,
ecological and social security indicators. Significant differences were found in
soil fertility status, pests and diseases management, risk and uncertainties, use
of agrochemicals and access to social services. No remarkable variations were
found in crop diversification, annual agricultural income and food sufficiency.
However, uncertainty and risk in agricultural production is relatively low in
highland communities. The findings reveal that agriculture production alone is
not a viable livelihood option for agricultural watershed communities in Nepal.
The households growing crops with hired labour have relatively sustainable
livelihoods in Nepal's agricultural watersheds. Insufficient agricultural land,
insufficient working manpower within a family, and lack of access to ecological
agricultural services are prime factors in being livelihood insecure in
agricultural watershed communities. Therefore, long-term policies and plans need
to be developed for the empowerment of local farmers and to support rural
livelihoods with adaptable and flexible income-generating strategies, resilient
resource management institutions and enhancement of knowledge, skills and social
capital.
PMID- 17030405
TI - Coeliac disease and risk of mood disorders--a general population-based cohort
study.
AB - BACKGROUND: Earlier research has indicated a positive association between coeliac
disease (CD) and some mental disorders. Studies on CD and depression have
inconsistent findings and we know of no study of CD and the risk of bipolar
disorder (BD). METHODS: We used Cox regression to investigate the risk of
subsequent mood disorders (MD); depression and BD in 13,776 individuals with CD
and 66,815 age- and sex-matched reference individuals in a general population
based cohort study in Sweden. We also studied the association between prior MD
and CD through conditional logistic regression. RESULTS: CD was associated with
an increased risk of subsequent depression (Hazard ratio (HR)=1.8; 95% CI=1.6
2.2; p<0.001, based on 181 positive events in individuals with CD and 529
positive events in reference individuals). CD was not associated with subsequent
BD (HR=1.1; 95% CI=0.7-1.7; p=0.779, based on 22 and 99 positive events).
Individuals with prior depression (OR=2.3; 95% CI=2.0-2.8; p<0.001) or prior BD
(OR=1.7; 95% CI=1.2-2.3; p=0.001) were at increased risk of a subsequent
diagnosis of CD. LIMITATIONS: Study participants with CD and MD may have more
severe disease than the average patient with these disorders since they were
identified through a hospital-based register. CONCLUSIONS: CD is positively
associated with subsequent depression. The risk increase for CD in individuals
with prior depression and BD may be due to screening for CD among those with MD.
PMID- 17030406
TI - Looking back at PCPT: looking forward to new paradigms in prostate cancer
screening and prevention.
AB - OBJECTIVES: Provide a critical summary of the latest interpretation of findings
from the Prostate Cancer Prevention Trial (PCPT). METHODS: Findings from PCPT and
recently published post-hoc analyses are reviewed. RESULTS: PCPT demonstrated
that finasteride can reduce the prevalence of prostate cancer, permitted the
first large-scale assessment of the performance characteristics of prostate
specific antigen for prostate cancer screening, and identified new-onset erectile
dysfunction as an early predictor of cardiovascular events. CONCLUSIONS: PCPT has
and will continue to yield valuable information regarding future strategies for
prostate cancer prevention and detection, benign prostatic hyperplasia, and other
matters of public health importance.
PMID- 17030407
TI - Kinetics of mouse antibody and lymphocyte responses during intranasal vaccination
with a lipooligosaccharide-based conjugate vaccine.
AB - We investigated the kinetics of humoral immunity and its related cellular immune
responses to intranasal (IN) immunization with a detoxified lipooligosaccharide
(dLOS)-tetanus toxoid (TT) conjugate against nontypeable Haemophilus influenzae
(NTHi) in mice. IN vaccination with dLOS-TT elicited high titers of LOS-specific
IgA in nasal washes and IgG in sera during a course of 4 inoculations while high
titers of TT-specific IgA and IgG were found in sera. A significant increase of
LOS-specific IgA antibody forming cells (AFCs) was observed in nasopharyngeal
associated lymphoid tissue (NALT) and nasal passages. However, TT induced broad
responses with higher numbers of IgA and IgG AFCs found in NALT and nasal
passages, less but significant IgA AFCs in cervical lymphoid nodes (CLN), spleen,
and lungs. Phenotypic analysis revealed a significant rise of total B220+ B
lymphocytes in NALT and CLN, particularly a rise in IgA+/IgM+ cells in the NALT
after the immunization. The latter result was complied with a significant rise of
IL-4 but not IFN-gamma positive CD4+ T-lymphocytes in NALT. Analysis of IgG
antibody subclasses showed that an IgG1 response to both LOS and TT epitopes
dominated in serum when compared to IgG2a. These kinetic antibody patterns and
cellular responses may provide useful information regarding to effective mucosal
vaccines against NTHi infections.
PMID- 17030408
TI - The linear allometric relationship between total metabolic energy per life span
and body mass of mammals.
AB - The aim of this study is to establish and calculate the exact allometric
relationship between the total metabolic energy per life span and the body mass
in a wide range of mammals with about six orders of magnitude variation of the
body mass of animals. The study shows that it exists a linear relationship
between the total metabolic energy per life span PT(ls) (kJ) and the body mass M
(kg) of 95 mammals (3 monotremes, Subclass Prototheria, 16 marsupialis (Subclass
Theria, Infraclass Metatheria) and 76 placentals (Subclass Theria, Infraclass
Eutheria)) from type: PT(ls)=A(ls)(+)M(1.0511), where P (kJ/day) is the basal
rate of metabolism and T(ls) (days) is the mean life span of animals. The linear
coefficient A(ls)(+)=7.158x10(5) kJ/kg is the total metabolic energy, exhausted
during the life span per 1 kg body mass of the animals. The mean values of the
total metabolic energy per life span, per unit body mass (A(ls)) for orders from
Subclass Prototheria and Theria (Infraclass Metatheria) and orders Xenarthra,
Pholidota, Soricomorpha, Rodentia (Infraclass Eutheria) varied negligible in
interval (4.656-5.80)x10(5) kJ/kg. The coefficient A(ls) grows from (7.68
8.36)x10(5) kJ/kg in Lagomorpha and Artiodactyla (Eutheria) to (10.58
12.64)x10(5) kJ/kg in orders Carnivora, Pinnipeda and Chiroptera (Eutheria).
A(ls) grows maximum to 18.5x10(5) kJ/kg in Primates. Thus, the values of
coefficient A(ls) differ maximum four-fold in all orders. Across the all species
the values of A(ls) are changes about one order of magnitude. Consequently, our
survey shows that the changes of the body mass, basal metabolic rate and the life
span of animals are three mutually related parameters, so that the product
A(ls)=(PT(ls))/M remains relatively constant in comparison to 1 million fold
difference in body mass and total metabolic energy per life span between mammals.
PMID- 17030410
TI - Comparison of analytical error and sampling error for contaminated soil.
AB - Investigation of soil from contaminated sites requires several sample handling
steps that, most likely, will induce uncertainties in the sample. The theory of
sampling describes seven sampling errors that can be calculated, estimated or
discussed in order to get an idea of the size of the sampling uncertainties. With
the aim of comparing the size of the analytical error to the total sampling
error, these seven errors were applied, estimated and discussed, to a case study
of a contaminated site. The manageable errors were summarized, showing a range of
three orders of magnitudes between the examples. The comparisons show that the
quotient between the total sampling error and the analytical error is larger than
20 in most calculation examples. Exceptions were samples taken in hot spots,
where some components of the total sampling error get small and the analytical
error gets large in comparison. Low concentration of contaminant, small extracted
sample size and large particles in the sample contribute to the extent of
uncertainty.
PMID- 17030409
TI - The cAMP response element binding protein (CREB) as an integrative HUB selector
in metazoans: clues from the hydra model system.
AB - In eukaryotic cells, a multiplicity of extra-cellular signals can activate a
unique signal transduction system that at the nuclear level will turn on a
variety of target genes, eliciting thus diverse responses adapted to the initial
signal. How distinct signals can converge on a unique signalling pathway that
will nevertheless produce signal-specific responses provides a theoretical
paradox that can be traced back early in evolution. In bilaterians, the CREB
pathway connects diverse extra-cellular signals via cytoplasmic kinases to the
CREB transcription factor and the CBP co-activator, regulating according to the
context, cell survival, cell proliferation, cell differentiation, pro-apoptosis,
long-term memory, hence achieving a "hub" function for cellular and developmental
processes. In hydra, the CREB pathway is highly conserved and activated during
early head regeneration through RSK-dependent CREB phosphorylation. We show here
that the CREB transcription factor and the RSK kinase are co-expressed in all
three hydra cell lineages including dividing interstitial stem cells,
proliferating nematoblasts, proliferating spermatogonia and spermatocytes,
differentiating and mature neurons as well as ectodermal and endodermal
myoepithelial cells. In addition, CREB gene expression is specifically up
regulated during early regeneration and early budding. When the CREB function was
chemically prevented, the early post-amputation induction of the HyBraI gene was
no longer observed and head regeneration was stacked. Thus, in hydra, the CREB
pathway appears already involved in multiple tasks, such as reactivation of
developmental programs in an adult context, self-renewal of stem cells,
proliferation of progenitors and neurogenesis. Consequently, the hub function
played by the CREB pathway was established early in animal evolution and might
have contributed to the formation of an efficient oral pole through the
integration of the neurogenic and patterning functions.
PMID- 17030411
TI - Aerobic digestion of starch wastewater in a fluidized bed bioreactor with low
density biomass support.
AB - A solid-liquid-gas, multiphase, fluidized bed bioreactor with low density
particles was used in this study to treat the high organic content starch
industry wastewater. The characteristics of starch wastewater were studied. It
shows high organic content and acidic nature. The performance of a three phase
fluidized bed bioreactor with low density biomass support was studied under
various average initial substrate concentrations, by varying COD values (2250,
4475, 6730 and 8910 mg/L) and for various hydraulic retention times (8, 16, 24,
32 and 40 h) based on COD removal efficiency. The optimum bed height for the
maximum COD reduction was found to be 80 cm. Experiments were carried out in the
bioreactor at an optimized bed height, after the formation of biofilm on the
surface of low-density particles (density=870 kg/m(3)). Mixed culture obtained
from the sludge, taken from starch industry effluent treatment plant, was used as
the source for microorganisms. From the results it was observed that increase in
initial substrate concentration leads to decrease in COD reduction and COD
reduction increases with increase in hydraulic retention time. The optimum COD
removal of 93.8% occurs at an initial substrate concentration of 2250 mg/L and
for the hydraulic retention time of 24h.
PMID- 17030413
TI - Phosphate removal using sludge from fuller's earth production.
AB - This study assesses the phosphate removal capacity and mechanism of precipitation
or adsorption from aqueous solutions in batch experiments by an industrial sludge
containing gypsum (CaSO(4).2H(2)O) obtained as a by-product from a fuller's earth
process. The potential capacity for phosphate removal was tested using various
solution concentrations, pH values, reaction times, and amount of sludge. The
maximum phosphate adsorption capacity calculated using the Langmuir equation was
2.0 g kg(-1). The pH for the maximum adsorption by the sludge was neutral to
alkaline (pH 7-12). Over 99% of phosphate was removed from a phosphate solution
of 30 mg L(-1) using 0.15 g of sludge in a 9-h reaction. Sulfate (SO(4)(2-))
concentration increased with increasing initial phosphate concentration, possibly
because of dissolution of gypsum and adsorption of both sulfate and phosphate. At
high phosphate concentration (>1000 mg L(-1)), relative constant concentration of
Ca(2+) was not consistent with adsorption of the most important phosphate removal
mechanism. Results suggest that precipitation of calcium phosphate is principally
responsible for phosphate removal under its high concentration. Agglomerated
precipitate in the reaction sludge was observed by SEM and identified as brushite
(CaHPO(4).2H(2)O) by XRD, FT-IR, and DTA. Based on thermodynamic considerations,
it is suggested that the brushite will readily transform to more stable phases,
such as hydroxyapatite (Ca(5)(PO(4))(3).OH).
PMID- 17030412
TI - Synthesis and characterization of a new inorganic cation-exchanger-Zr(IV)
tungstomolybdate: analytical applications for metal content determination in real
sample and synthetic mixture.
AB - An amorphous sample of inorganic cation-exchanger Zr(IV) tungstomolybdate was
prepared by mixing varying ratios of 0.1M aqueous solution of sodium tungstate
and 0.1M aqueous solution of sodium molybdate into 0.1M aqueous solution of
zirconium oxychloride at pH 1. This cation-exchanger was found to have a good ion
exchange capacity (2.40 mequiv.g(-1) for Na(+)), high thermal and chemical
stability. A tentative structural formula was proposed on the basis of chemical
composition, FTIR and thermogravimetric analysis. Distribution coefficients
(K(d)) values of metal ions in various solvent systems were determined. Some
important and analytically difficult quantitative binary separations viz. Ni(II)
Pb(II), Ni(II)-Zn(II), Ni(II)-Cd(II), Mg(II)-Al(III), etc. were achieved. The
practical applicability of the cation-exchanger was demonstrated in the
separation of Cu(II)-Zn(II) from a synthetic mixture as well as from real samples
of pharmaceutical formulation and brass alloy.
PMID- 17030414
TI - Improving the performance of sequencing batch reactor (SBR) by the addition of
zeolite powder.
AB - Two types of operation means "SBR reactor alone (control reactor)" and "adding
zeolite powder into SBR reactor (test reactor)" were used to treat municipal
wastewater. The test results revealed that zeolite powder addition could improve
the activity of the activated sludge. It was investigated the specific oxygen
utilization rate (SOUR) of the tested zeolite sludge were about double times that
of the control activated sludge, and the nitrification rate and settling property
of zeolite-activated sludge were both improved. Due to the combination of zeolite
adsorption for NH(4)(+)-N and enhanced simultaneous nitrification and de
nitrification (SND), a higher nitrogen removal was observed in test reactor
compared to the control reactor, and the addition of zeolite powder is helpful to
inhabit sludge bulking. In addition, through long-term parallel shock load test,
it was found that the zeolite powder addition could enhance the ability of
activated sludge in resisting the shock load of organics and ammonium. Compared
to the control activated sludge, zeolite powder added activated sludge could
remove COD, NH(4)(+)-N, TN and TP significantly in a shorter cycle time. At the
same operational time period, the test SBR could treat wastewater quantity 1.22
times that treated in control SBR.
PMID- 17030415
TI - Removal of C.I. Acid Orange 7 from aqueous solution by UV irradiation in the
presence of ZnO nanopowder.
AB - The removal of C.I. Acid Orange 7 (AO7) from aqueous solution under UV
irradiation in the presence of ZnO nanopowder has been studied. The average
crystallite size of ZnO powder was determined from XRD pattern using the Scherrer
equation in the range of 33 nm. The experiments showed that ZnO nanopowder and UV
light had a negligible effect when they were used on their own. The effects of
some operational parameters such as pH, the amount of ZnO nanopowder and initial
dye concentration were also examined. The photodegradation of AO7 was enhanced by
the addition of proper amount of hydrogen peroxide, but it was inhibited by
ethanol. From the inhibitive effect of ethanol, it was deducted that hydroxyl
radicals played a significant role in the photodegradation of the dye. The
kinetic of the removal of AO7 can be explained in terms of the Langmuir
Hinshelwood model. The values of the adsorption equilibrium constant, K(AO7), and
the kinetic rate constant of surface reaction, k(c), were 0.354(mg l(-1))(-1) and
1.99 mg l(-1)min(-1), respectively. The electrical energy consumption per order
of magnitude for photocatalytic degradation of AO7 was lower in the
UV/ZnO/H(2)O(2) process than that in the UV/ZnO process. Accordingly, it could be
stated that the complete removal of color, after selecting desired operational
parameters could be achieved in a relatively short time, about 60 min.
PMID- 17030416
TI - Potential use of a combined ozone and zeolite system for gaseous toluene
elimination.
AB - This study investigated the performance of a combined ozone and zeolite system in
eliminating gaseous toluene which is a major contaminant in many industrial and
indoor environments. The hypothesis that the removal of toluene by ozone can be
substantially affected by confining the oxidation reaction in a zeolite structure
was evaluated. The degradation of toluene seemed to be contributed by the active
oxygen atom generated from the decomposition of ozone at the Lewis acid sites in
the zeolite 13X. Air containing toluene levels at 1.5, 2 and 3 ppm was injected
with ozone in the range of 0-6 ppm before being vented into a fixed amount of
3600 g zeolite 13X with 90 mm bed-length. The experimental results showed that
the elimination rate of toluene was significantly enhanced when compared to using
zeolite or ozone alone. In particular, over 90% of the 1.5 ppm toluene was
removed when 6 ppm ozone was used at 40% relative humidity level. Deactivation of
the zeolite 13X after a few hours of reactions under the current experimental
conditions was probably due to the adsorbed water, carbon dioxide and the
reaction by-products. The residue species left in the zeolite and the
intermediate species in the exhaust gas stream were characterized by FT-IR, GC-MS
and HP-LC methods, respectively. A distinctive peak of O atom attached to the
Lewis acid site at 1380 cm(-1) was found in the FT-IR spectrum and trace amount
of aldehydes was found to be the reaction by-products.
PMID- 17030417
TI - Hexavalent chromium removal from wastewater using aniline formaldehyde condensate
coated silica gel.
AB - A resinous polymer, aniline formaldehyde condensate (AFC) coated on silica gel
was used as an adsorbent in batch system for removal of hexavalent chromium from
aqueous solution by considering the effects of various parameters like reaction
pH, dose of AFC coated silica gel, initial Cr(VI) concentration and aniline to
formaldehyde ratio in AFC synthesis. The optimum pH for total chromium [Cr(VI)
and Cr(III)] adsorption was observed as 3. Total chromium adsorption was second
order and equilibrium was achieved within 90-120 min. Aniline to formaldehyde
ratio of 1.6:1 during AFC synthesis was ideal for chromium removal. Total
chromium adsorption followed Freundlich's isotherm with adsorption capacity of 65
mg/g at initial Cr(VI) 200mg/L. Total chromium removal was explained as
combinations of electrostatic attraction of acid chromate ion by protonated AFC,
reduction of Cr(VI) to Cr(III) and bond formation of Cr(III) with nitrogen atom
of AFC. Almost 40-84% of adsorbed chromium was recovered during desorption by
NaOH, EDTA and mineral acids. AFC coated silica gel can be effectively used for
treatment of chromium containing wastewaters as an alternative.
PMID- 17030418
TI - Predicting pressure drop in venturi scrubbers with artificial neural networks.
AB - In this study a new approach based on artificial neural networks (ANNs) has been
used to predict pressure drop in venturi scrubbers. The main parameters affecting
the pressure drop are mainly the gas velocity in the throat of venturi scrubber
(V(g)(th)), liquid to gas flow rate ratio (L/G), and axial distance of the
venturi scrubber (z). Three sets of experimental data from five different venturi
scrubbers have been applied to design three independent ANNs. Comparing the
results of these ANNs and the calculated results from available models shows that
the results of ANNs have a better agreement with experimental data.
PMID- 17030419
TI - Heavy metal leaching from aerobic and anaerobic landfill bioreactors of co
disposed municipal solid waste incineration bottom ash and shredded low-organic
residues.
AB - In this study, heavy metal leaching from aerobic and anaerobic landfill
bioreactor test cells for co-disposed municipal solid waste incineration (MSWI)
bottom ash and shredded low-organic residues has been investigated. Test cells
were operated for 1 year. Heavy metals which were comparatively higher in
leachate of aerobic cell were copper (Cu), lead (Pb), boron (B), zinc (Zn),
manganese (Mn) and iron (Fe), and those apparently lower were aluminum (Al),
arsenic (As), molybdenum (Mo), and vanadium (V). However, no significant release
of heavy metals under aerobic conditions was observed compared to anaerobic and
control cells. Furthermore, there was no meaningful correlation between oxidation
reduction potential (ORP) and heavy metal concentrations in the leachates
although some researchers speculate that aeration may result in excessive heavy
metal leaching. No meaningful correlation between dissolved organic carbon (DOC)
and leaching of Cu and Pb was another interesting observation. The only heavy
metal that exceeded the state discharge limits (10mg/l, to be enforced after
April 2005) in the aerobic cell leachate samples was boron and there was no
correlation between boron leaching and ORP. Higher B levels in aerobic cell
should be due to comparatively lower pH values in this cell. However, it is
anticipated that this slightly increased concentrations of B (maximum 25mg/l)
will not create a risk for bioreactor operation; rather it should be beneficial
for long-term stability of the landfill through faster washout. It was concluded
that aerobization of landfills of heavy metal rich MSWI bottom ash and shredded
residues is possible with no dramatic increase in heavy metals in the leachate.
PMID- 17030420
TI - Speciation of Cr(III) and Cr(VI) after column solid phase extraction on Amberlite
XAD-2010.
AB - A speciation procedure for Cr(III) and Cr(VI) based on column solid phase
extraction on Amberlite XAD-2010 and flame atomic absorption spectrometry
combination. Cr(VI) was quantitatively recovered on Amberlite XAD-2010 resin at
pH range of 2.0-3.0 as its diethyldithiocarbamate complex, while the recoveries
of Cr(III) was below 5%. The influences of the various parameters including
amounts of the reagents, eluent type and its volume, sample volume, etc., on the
quantitative recoveries were examined. The interference of matrix and coexistent
elements for method were studied. The detection limit (corresponding to three
times the standard deviation of the blank) and the enrichment factor for Cr(VI)
were found to be 1.28 microg/L and 25, respectively. To verify the accuracy of
the method, drinking water certified reference material (CRM-TMDW-500) was
analyzed and the results obtained were in good agreement with the certified
value. The proposed method has been successfully applied to the speciation of
Cr(III) and Cr(VI) in water samples and preconcentration of total chromium in
environmental samples.
PMID- 17030422
TI - Adsorption of p-nitrophenol from aqueous solutions onto activated carbon fiber.
AB - The adsorption of p-nitrophenol (PNP) onto activated carbon fiber (ACF) was
investigated in simulated wastewater in a batch system to evaluate the effects of
solution pH, presence of sodium chloride, adsorbent doses and temperature. It was
found that PNP adsorption amount depended on pH, sodium chloride content,
adsorbent doses and temperature. Langmuir and Freundlich models were applied to
describe the adsorption isotherms. Freundlich model agreed with experimental data
well, indicating the possibility of more than just one monomolecular layer of
coverage. SEM photographs of ACF before and after adsorption revealed that it was
in part with multimolecular layers of coverage on ACF surfaces. The change of
free energy, enthalpy, and entropy of adsorption were also evaluated for the
adsorption process. The pseudo-first-order and pseudo-second-order kinetic models
were used to describe the kinetic data. The experimental data fitted very well
the pseudo-second-order kinetic model. Attempts were made to desorb PNP from ACF
using dilute NaOH solution and water, and desorption efficiency was obtained to
the extent of 92.7% with 0.025 M NaOH and water at 368 K.
PMID- 17030421
TI - Sorption kinetics and chemical forms of Cd(II) sorbed by thiol-functionalized 2:1
clay minerals.
AB - The interaction between Cd(II) in aqueous solution and two 2:1 expandable clay
minerals (i.e., montmorillonite and vermiculite), showing different layer charge,
was addressed via batch sorption experiments on powdered clay minerals both
untreated and amino acid (cysteine) treated. Reaction products were characterized
via X-ray powder diffraction (XRDP), chemical analysis (elemental analysis and
atomic absorption spectrophotometry), thermal analysis combined with evolved
gases mass spectrometry (TGA-MSEGA) and synchrotron-based X-ray absorption
spectroscopy via extended X-ray absorption fine structure (EXAFS)
characterization. Sorption isotherms for Cd(II) in presence of different
substrates, shows that Cd(II) uptake depends both on Cd(II) starting
concentration and the nature of the substrate. Thermal decomposition of Cd
cysteine treated clay minerals evidences the evolution of H(2)O, H(2)S, NO(2),
SO(2), and N(2)O(3). These results are well consistent with XRDP data collected
both at room and at increasing temperature and further stress the influence of
the substrate, in particular cysteine, on the interlayer. EXAFS studies suggest
that Cd(II) coordinates with oxygen atoms, to give monomer complexes or CdO
molecules, either on the mineral surface and/or in the interlayer. For Cd
cysteine complexes EXAFS data agree with the existence of Cd-S clusters, thus
suggesting a predominant role of the thiol group in the bonding of Cd with the
amino acid.
PMID- 17030423
TI - Distribution of copper in the vicinity of a deactivated mining site at Carajas in
the Amazon region of Brazil.
AB - In this work the re-fixation of mobilized copper (Cu) that was released from a
deactivated pilot Cu ore dressing plant in the tropical rain forest at
Southeastern Amazon (Carajas) was studied. Samples of top soils, decay leaf
litter deposited on soils, roots and leaves of standing biomass were taken for
the determination of Cu concentration in order to evaluate the distribution of it
between different environmental compartments. In the sampling points near to the
now extinct plant, total Cu concentrations in the soil reached an average value
of 2140 microg g(-1) above the natural level of about 40 microg g(-1), being that
bioavailable Cu estimated by DTPA method varied from 1.9 to 20.7% of this total.
From the data was possible to calculate that the soil compartment is able to hold
around 10 kg Cu/m(2) of ground. Roots of the standing biomass in that area hold
around 17 g Cu/m(2), while the Cu content in leaves showed to be largely
independent of the Cu level in the soil. Copper in the leaves was estimated as
around 1g/m(2) of ground area. In turn, the decay leaf litter deposited on soil
can hold about 1.6 g Cu/m(2). The terrestrial system surrounding the abandoned
pilot plant demonstrated great buffer capacity to retain mobile Cu released by
anthropogenic activities in the area.
PMID- 17030424
TI - Degradation of hexachlorobenzene by electron beam irradiation.
AB - Hexachlorobenzene removal efficiencies in different solvents by electron beam
irradiation were investigated. Several factors that might affect the removal
efficiencies were further examined. At 10 kGy, HCB degradation value was 85.8% in
the solvent of acetone:water mixture (20:80, v/v), while at the same dose, the
reduction value of 42.6% was achieved in hexane solvent. In the solvent of
acetone:water mixture (20:80, v/v), Na(2)CO(3) as additive could enhance the
degradation efficiency by 4.5%. However, Triton X-100, NaNO(3), NaNO(2) and
H(2)O(2) as additives reduced the degradation value by 20.0%, 6.3%, 85.7% and
20.5%, respectively. Furthermore, the increase of these additives would result in
the decrease of the degradation efficiencies. The pH value of the solvent of
acetone:water mixture (20:80, v/v) could affect HCB removal efficiency. At pH
11.8, reduction value of 90.2% was achieved at 10 kGy, while at the same dose, at
pH 2.7 and 6.8, the reduction values were only 82.4% and 86.9%, respectively. At
the same time, the degradation value of pentachlorobenzene was 94.7% at 10 kGy.
In the presence or absence of additives, pH value of the solvent of acetone:water
mixture (20:80, v/v) became lower with increasing dose after electron beam
irradiation.
PMID- 17030425
TI - The removal of Cu(II) and Co(II) from aqueous solutions using cross-linked
chitosan--evaluation by the factorial design methodology.
AB - A 2(3) factorial design was employed to evaluate the quantitative removal of
Cu(II) and Co(II) on glutaraldehyde-cross-linked chitosan from kinetic isotherms,
using chitosan masses of 100 and 300mg and temperatures of 25 and 35 degrees C.
The adsorption parameters were analyzed statistically using modeling polynomial
equations and a cumulative normal probability plot. The results indicated the
higher quantitative preference of the chitosan for Cu(II) in relation to Co(II).
Increasing the chitosan mass decreases the adsorption/mass ratio (mol g(-1)) for
both metals. The principal effect of the temperature did not show statistical
importance. The adsorption thermodynamic parameters, namely Delta(ads)H,
Delta(ads)G and Delta(ads)S, were determined. Exothermic and endothermic results
were found in relation to a specific factorial design experiment. A comparison of
Delta(ads)H values was made in relation to some metal-adsorbent interactions in
literature. It is suggested that the adsorption thermodynamic parameters are
determined by the influence of the principal and interactive experimental
parameters and not by the temperature changes alone.
PMID- 17030426
TI - The use of slurry sampling for the determination of manganese and copper in
various samples by electrothermal atomic absorption spectrometry.
AB - Manganese and copper in multivitamin-mineral supplements and standard reference
materials were determined by slurry sampling electrothermal atomic absorption
spectrometry. Slurries were prepared in an aqueous solution containing Triton X
100. The effects of different parameters such as ratio of solid to liquid phase
volume, total slurry volume and addition of Triton X-100 as a dispersant on the
analytical results were investigated. The graphite furnace programs were
optimized for slurry sampling depending on the analytes and their concentrations
in the samples. The linear calibration method with aqueous standard solutions was
used for the quantification. At optimum experimental conditions, R.S.D. values
were below 5%. The analytes were determined in the limits of 95% confidence level
with respect to certified values in coal and soil standard reference materials
and to those found by wet-digestion in multivitamin-mineral supplements.
Detection limits (3delta) for Mn and Cu were 0.10 microg L(-1) and 1.82 microg L(
1) for 10 microL coal standard reference material slurry, respectively.
PMID- 17030427
TI - Sulphur mustard vapor breakthrough behaviour on reactive carbon systems.
AB - Breakthrough behaviour of sulphur mustard, the deadliest of persistent chemical
warfare agents, on carbon systems such as NaOH/CrO(3)/C, NaOH/CrO(3)/EDA/C and
RuCl(3)/C has been studied and the data were compared with that of active carbon.
Effects of bed lengths of carbons on breakthrough time have also been correlated.
Thereafter, the effects of flow rate of air-sulphur mustard mixture,
concentration and temperature on the kinetic parameters such as rate constant
(k(v)) and kinetic saturation capacity (W(e)) were analyzed and interpreted by
means of modified Wheeler equation. Rate constant was found to be increasing
while W(e) was found to be invariable with the increase in air flow rate. Both
k(v) and W(e) decreased with the increase of temperature, however, no significant
effect on W(e) and k(v) was observed due to concentration change (0.3-0.6 mg/l).
The values of kinetic saturation capacity were used to predict the service
lives/breakthrough times of carbon beds (when used in filtration systems).
PMID- 17030428
TI - Region-specific regulation of inflammation and pathogenesis in experimental
autoimmune encephalomyelitis.
AB - Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple
sclerosis and is characterized by an infiltrate of predominantly T cells and
macrophages in the spinal cord and brain. In both the spinal cord and the
cerebellum, Th1 cells direct inflammation to antigen-rich white matter tracts,
and there is a TNFR1-dependent recruitment of CD11b(hi) cells in both regions. In
the spinal cord, parenchymal invasion, demyelination and clinical symptoms are
associated with TNFR1-dependant parenchymal induction (especially astrocytes) of
VCAM-1 and CXCL2. None of these events occur in the cerebellum despite the fact
that an inflammatory infiltrate accumulates in the perivascular space. Therefore
regional specificity in astrocyte responses to inflammatory cytokines may
regulate regional parenchymal infiltration and pathogenesis.
PMID- 17030429
TI - Targeting adenosine A2A receptors in Parkinson's disease.
AB - The adenosine A2A receptor has emerged as an attractive non-dopaminergic target
in the pursuit of improved therapy for Parkinson's disease (PD), based in part on
its unique CNS distribution. It is highly enriched in striatopallidal neurons and
can form functional heteromeric complexes with other G-protein-coupled receptors,
including dopamine D2, metabotropic glutamate mGlu5 and adenosine A1 receptors.
Blockade of the adenosine A2A receptor in striatopallidal neurons reduces
postsynaptic effects of dopamine depletion, and in turn lessens the motor
deficits of PD. A2A antagonists might partially improve not only the symptoms of
PD but also its course, by slowing the underlying neurodegeneration and reducing
the maladaptive neuroplasticity that complicates standard 'dopamine replacement'
treatments. Thus, we review here a prime example of translational neuroscience,
through which antagonism of A2A receptors has now entered the arena of clinical
trials with realistic prospects for advancing PD therapeutics.
PMID- 17030430
TI - Genetic mouse models for studying inhibitors of spinal axon regeneration.
AB - The laboratory mouse has emerged as a primary model organism for studying axon
regeneration after experimental spinal cord injury, owing to its genetic
amenability. Mutant mouse models are contributing significantly to our
understanding of the molecular mechanisms of axon regeneration failure in the
adult mammalian central nervous system (CNS), in particular regarding the role of
axon-growth inhibitors. Here, we discuss recent advances in understanding axon
regeneration failure that have been made using genetically modified mice,
focusing on the inhibitory influences in the CNS, and we illustrate the
advantages of using the mouse as a surrogate organism to study axon regeneration
and spinal cord repair.
PMID- 17030431
TI - Molecular programming of stem cells into mesodiencephalic dopaminergic neurons.
AB - In a screen for homeobox transcription factors expressed in the embryonic ventral
midbrain, Andersson et al. recently identified Lmx1a and Msx1. Using in ovo
electroporation in chick embryos, they showed that these factors are crucial for
initiating the differentiation of neuroepithelial progenitor neurons into
mesodiencephalic dopaminergic (mdDA) neurons. Lmx1a also initiated a
developmental program that drove an mdDA phenotype in mouse embryonic stem cells.
This indicates that these factors can be exploited in cell-replacement strategies
for treatment of Parkinson's disease.
PMID- 17030432
TI - Intracellular messengers involved in spontaneous pain, heat hyperalgesia, and
mechanical allodynia induced by intrathecal dihydroxyphenylglycine.
AB - We investigated the role of two intracellular second messengers, extracellular
signal-regulated protein kinase (ERK) and protein kinase C (PKC), in a model of
persistent pain using intrathecal (i.t.) (R,S)-3,5-dihydroxyphenylglycine (DHPG).
Spontaneous nociceptive behaviours (SNBs), mechanical allodynia (von Frey
thresholds) and heat hyperalgesia (plantar test latencies) induced by DHPG were
measured in animals pretreated i.t. with membrane permeable inhibitors of ERK (PD
98059) and PKC (GF 109203X). Spinal administration of PD 98059 dose-dependently
reduced SNBs, and attenuated both mechanical allodynia and heat hyperalgesia
induced by DHPG. GF 109203X treatment also reduced SNBs and heat hyperalgesia,
but did not affect mechanical allodynia induced by DHPG. Neither PD 98059, nor GF
109203X, altered mechanical or thermal thresholds in saline-injected control
rats. These results suggest that both ERK and PKC are involved in persistent pain
associated with the i.t. administration of DHPG.
PMID- 17030433
TI - Antioxidant N-acetylcysteine inhibits the activation of JNK3 mediated by the
GluR6-PSD95-MLK3 signaling module during cerebral ischemia in rat hippocampus.
AB - Cerebral ischemia induces kainate receptor glutamate receptor 6 (GluR6) binding
to the postsynaptic density protein 95 (PSD95), which in turn anchors mixed
lineage kinase 3 (MLK3) via SH3 domain in rat brain. MLK3 subsequently activates
c-Jun NH(2)-terminal kinase (JNK) via MAP kinase kinases (MKKs). In this study,
we investigated the association of PSD95 with GluR6 and MLK3, the
autophosphorylation of MLK3, the combination of MLK3 with JNK3, and the
phosphorylation of JNK3 during cerebral ischemia in rat hippocampus CA1. Our
results indicate that the GluR6-PSD95-MLK3 complex quickly enhanced at 5 min of
ischemia and peaked at 10 min of ischemia, and then gradually reduced with the
prolonged time of ischemia. Interestingly, the combination of MLK3 and JNK3
gradually increased from 5 min to 30 min of ischemia. JNK3 phosphorylation first
increased and then attenuated in cytosol, suggesting the translocation of
activated JNK3 to nucleus during ischemia. To further investigate the possible
mechanism of JNK3 activation, antioxidant N-acetylcysteine (NAC) was given to the
rats 20 min prior to ischemia. Results indicate that NAC distinctly inhibited the
association of PSD95 with GluR6 and MLK3, the autophosphorylation of MLK3, the
combination of MLK3 with JNK3 and JNK3 activation. Taken together, these finding
indicate that ischemic stimulation results in JNK3 activation through the GluR6
PSD95-MLK3 signaling module, and that the activation of JNK3 is closely related
to oxidative stress.
PMID- 17030434
TI - Severity level and injury track determine outcome following a penetrating
ballistic-like brain injury in the rat.
AB - Penetrating ballistic brain injury (PBBI) is a high-energy transfer wound causing
direct damage to the cerebrum. Outcome is directly related to the ballistic's
anatomical path and degree of energy transfer. In this study we evaluated
differences in outcome induced by altering the 'projectile' paths and severity
levels of a simulated bullet wound using a newly characterized rat model of PBBI.
Severity levels (5, 10, and 15%) were compared across three distinct injury
paths: (1) unilateral 'frontal', (2) 'bilateral' hemispheric, and (3) unilateral
'caudal' (including cerebellum/midbrain). Outcome was assessed by differences in
mortality rate and motor dysfunction (e.g. neurological and balance beam
deficits). Results indicated that outcome was dependent not only on the severity
level of PBBI (P<0.001, r=0.535) but also brain regions injured (P<0.001,
r=0.398). A unilateral caudal injury was associated with the highest degree of
mortality (up to 100%) and motor dysfunction (64-100% disability). Bilateral
hemispheric injuries were also potentially fatal, while the best outcomes were
associated with a unilateral frontal injury (no mortality and 14-39% motor
disability). These data closely resemble clinical reports of ballistic wounds to
the head and further validate the rat PBBI model with the ultimate intent to
investigate novel therapeutic approaches for diagnosis and treatment of the
neuropathological damage associated with PBBI.
PMID- 17030435
TI - Participation of peripheral group I and II metabotropic glutamate receptors in
the development or maintenance of IL-1beta-induced mechanical allodynia in the
orofacial area of conscious rats.
AB - The present study investigated the role of peripheral groups I and II
metabotropic glutamate receptors (mGluRs) in interleukin (IL)-1beta-induced
mechanical allodynia in the orofacial area of rats. Subcutaneous injection of 10
pg of IL-1beta decreased air-puff thresholds ipsilateral or contralateral to the
injection site. The decrease in air-puff thresholds appeared 10 min after the
injection of IL-1beta and IL-1beta-induced mechanical allodynia persisted for
over 3 h. Pre-treatment with 7-(hydroxyimino) cyclopropa[b] chromen-1a
carboxylate ethyl ester (CPCCOEt) or 2-methyl-6-(phenylethynyl)-pyridine
hydrochloride (MPEP), a mGluR1 or mGluR5 antagonist, blocked IL-1beta-induced
mechanical allodynia and mirror-image mechanical allodynia produced by a
subcutaneous injection of 10 pg of IL-1beta. However, post-treatment with CPCCOEt
or MPEP did not affect changes in behavioral responses, which were produced by
the IL-1beta injection. Pre-treatment, as well as post-treatment with (2R,4R)-4
aminopyrrolidine-2,4-dicarboxylate (APDC), a group II mGluR agonist, blocked
either IL-1beta-induced mechanical allodynia or mirror-image mechanical
allodynia. The anti-allodynic effects of APDC were abolished by pre-treatment
with (2S)-2-amino-2[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic
acid (LY341495), a group II mGluR antagonist. These results indicate that
peripheral group II mGluRs are involved in the development and maintenance of IL
1beta-induced mechanical allodynia, while peripheral group I mGluRs are involved
in the development of IL-1beta-induced mechanical allodynia. Based on our
observations, the peripheral application of group II mGluR agonists may be of
therapeutic value in treating inflammatory pain.
PMID- 17030436
TI - Intracellular location of the ABC transporter PRP1 related to pentamidine
resistance in Leishmania major.
PMID- 17030438
TI - Pain relief by applying transcutaneous electrical nerve stimulation (TENS) on
acupuncture points during the first stage of labor: a randomized double-blind
placebo-controlled trial.
AB - Transcutaneous electrical nerve stimulation (TENS) is one of the non
pharmacological means of pain relief for labor and delivery. We aimed to
investigate the efficacy and safety of TENS on specific acupuncture points for
reducing pain in the first stage of labor. In this double-blind, placebo
controlled trial, we randomly assigned healthy full-term parturients in active
phase of first-stage labor to either TENS on four acupuncture points (Hegu [Li 4]
and Sanyinjiao [Sp 6]) (n=52) or the TENS placebo (n=53). Visual analogue scale
(VAS) was used to assess pain before and 30 and 60 min after treatment. The
primary outcome was the rate of VAS score decrease 3 in each group. A
questionnaire was given at 24h post-partum to evaluate the satisfaction of pain
relieving method and the willingness to have the same treatment again. Mode of
delivery and neonatal effect were measured as secondary outcome. One hundred
women were eligible for analysis. TENS group experienced VAS score reduction 3
significantly more common than the TENS placebo group (31/50 [62%] vs 7/50 [14%],
P<0.001). Willingness of using the same analgesic method for a future childbirth
was also significantly different (TENS: 48/50 [96%] vs TENS placebo: 33/50 [66%],
P<0.001). Operative delivery was increased in the TENS group (12/50 [24%] vs 4/50
[8%], P=0.05), but the neonatal outcomes were not different. The application of
TENS on specific acupuncture points could be a non-invasive adjunct for pain
relief in the first stage of labor.
PMID- 17030437
TI - Activity-dependent slowing of conduction velocity in uninjured L4 C fibers
increases after an L5 spinal nerve injury in the rat.
AB - Growing evidence suggests that uninjured afferents may play an important role in
neuropathic pain following nerve injury. The excitability of nociceptive neurons
in the L4 spinal nerve appears to be enhanced following an injury to the adjacent
L5 spinal nerve. In this study, we investigated whether the action-potential
conduction properties of unlesioned, unmyelinated fibers are also altered. A
teased-fiber technique was used to record from single C fibers from the L4 spinal
nerve of the rat in vitro. Repeated electrical stimulation of the tibial nerve
was used to investigate activity-dependent slowing of conduction velocity. Twin
pulse stimulation at a 50 ms interpulse interval allowed investigation of
supranormal conduction velocity. Blinded experiments were performed 8-10 days
after sham surgery and after an L5 spinal nerve ligation (L5 SNL). Activity
dependent slowing revealed two populations of C fibers, a "nociceptor" population
with a large degree of activity-dependent slowing and a "non-nociceptor"
population with a smaller degree of activity-dependent slowing. Both populations
showed enhanced activity-dependent slowing of conduction velocity and enhanced
supranormal conduction velocities in lesioned animals compared to sham animals.
Activity-dependent slowing was also enhanced after an L5 SNL in the mouse. These
alterations in conduction velocity may reflect changes in expression of ion
channels responsible for the membrane excitability. These data provide additional
evidence that a nerve injury leads to persistent alterations in the properties of
adjacent uninjured, unmyelinated fibers.
PMID- 17030439
TI - Comparison of vibration perception thresholds in individuals with diffuse upper
limb pain and carpal tunnel syndrome.
AB - The study objective was to compare vibration perception and patterns of blood
flow in outpatients with diffuse upper limb pain disorder (ULPD), carpal tunnel
syndrome (CTS) and age and sex matched healthy controls. Vibration perception and
discrimination thresholds were compared in subjects with ULPD (n=27), CTS (n=27)
and healthy matched controls (n=54). Vibration measurements were taken
bilaterally at three sites: (a) over the dorsum of the second and (b) fifth
metacarpals and (c) the palmar aspect of the first and second metacarpals,
corresponding to the innervation territories of the radial, ulnar and median
nerves, respectively. Non-invasive assessments of peripheral blood flow were also
performed in both limbs. When compared to healthy controls, subjects with ULPD
had widespread elevation of vibration thresholds both ipsilateral and
contralateral to the symptomatic limb. Subjects with CTS had similarly elevated
vibration thresholds at sites both adjacent to and distant from the site of
peripheral nerve injury. The responses to cold pressor testing of the upper limbs
were physiologically normal in both the CTS and ULPD patient groups. Furthermore,
there were no significant differences in the haemodynamic responses between the
patient groups. The global elevation of vibration thresholds in subjects with
both ULPD and CTS is consistent with altered central nervous system mechanisms,
common to both conditions, which may be either adaptive to or maintaining the
perception of pain.
PMID- 17030440
TI - EFTEM assistant: a tool to understand the limitations of EFTEM.
AB - The first version of a free tool for Gatan's Digital Micrographtrade mark is
presented which aims to aid the energy-filtered TEM (EFTEM) community by
predicting and correcting the most common sources of degradation. The software
allows selection of either Krivanek's or Egerton's approach to account for the
spatial resolution degradation caused by the electron optical aberrations. The
effects of aberrations and signal 'delocalization' are combined to simulate the
blurring caused in EFTEM elemental maps. Two microstructural features with ideal
geometry are used to illustrate use of the software: spherical particles and
parallel sided interfaces. The software also allows the simulation of the effects
of the noise and drift in the final elemental map, independently or in
combination. It can be easily demonstrated that when the dimensions of the
feature of interest are comparable in scale to the image degradation factors, the
effects of the latter should not be neglected. More importantly, the software can
deconvolute the effects of the degradation factors, revealing the true dimensions
and signal intensity of the feature of interest.
PMID- 17030441
TI - Alpha,beta-dicarbonyl reduction by Saccharomyces D-arabinose dehydrogenase.
AB - An alpha,beta-dicarbonyl reductase activity was purified from Saccharomyces
cerevisiae and identified as the cytosolic enzyme D-Arabinose dehydrogenase
(ARA1) by MALDI-TOF/TOF. Size exclusion chromatography analysis of recombinant
Ara1p revealed that this protein formed a homodimer. Ara1p catalyzed the
reduction of the reactive alpha,beta-dicarbonyl compounds methylglyoxal,
diacetyl, and pentanedione in a NADPH dependant manner. Ara1p had apparent Km
values of approximately 14 mM, 7 mM and 4 mM for methylglyoxal, diacetyl and
pentanedione respectively, with corresponding turnover rates of 4.4, 6.9 and 5.9
s(-1) at pH 7.0. pH profiling showed that Ara1p had a pH optimum of 4.5 for the
diacetyl reduction reaction. Ara1p also catalyzed the NADP+ dependant oxidation
of acetoin; however this back reaction only occurred at alkaline pH values. That
Ara1p was important for degradation of alpha,beta-dicarbonyl substrates was
further supported by the observation that ara1-Delta knockout yeast mutants
exhibited a decreased growth rate phenotype in media containing diacetyl.
PMID- 17030442
TI - Plant peroxisomes as a source of signalling molecules.
AB - Peroxisomes are pleiomorphic, metabolically plastic organelles. Their essentially
oxidative function led to the adoption of the name 'peroxisome'. The dynamic and
diverse nature of peroxisome metabolism has led to the realisation that
peroxisomes are an important source of signalling molecules that can function to
integrate cellular activity and multicellular development. In plants defence
against predators and a hostile environment is of necessity a metabolic and
developmental response--a plant has no place to hide. Mutant screens are
implicating peroxisomes in disease resistance and signalling in response to
light. Characterisation of mutants disrupted in peroxisomal beta-oxidation has
led to a growing appreciation of the importance of this pathway in the production
of jasmonic acid, conversion of indole butyric acid to indole acetic acid and
possibly in the production of other signalling molecules. Likewise the role of
peroxisomes in the production and detoxification of reactive oxygen, and possibly
reactive nitrogen species and changes in redox status, suggests considerable
scope for peroxisomes to contribute to perception and response to a wide range of
biotic and abiotic stresses. Whereas the peroxisome is the sole site of beta
oxidation in plants, the production and detoxification of ROS in many cell
compartments makes the specific contribution of the peroxisome much more
difficult to establish. However progress in identifying peroxisome specific
isoforms of enzymes associated with ROS metabolism should allow a more definitive
assessment of these contributions in the future.
PMID- 17030443
TI - Comparative proteomic analysis reveals differential expression of Hsp25 following
the directed differentiation of mouse embryonic stem cells.
AB - Murine embryonic stem (ES) cells can be committed to neural differentiation with
high efficiency in culture through the use of feeder- and serum-free media. This
system is proving to be an excellent model to study processes involved in ES cell
commitment to neural cell fate. We used this approach to generate neurogenic
embryoid bodies (NEBs) in a serum-free culture system to perform proteomic
analysis of soluble fractions and identify early changes in protein expression as
ES cells differentiate. Ten candidate proteins were altered significantly in
expression levels. One of the most significant alterations was for the small heat
shock protein Hsp25. Three species of Hsp25 are detected in ES cells, and this
expression pattern changes during the first 24 h of differentiation until
expression is decreased to levels that are barely detectable at 4 days following
differentiation. We used immunofluorescence studies to confirm that following ES
cell differentiation, expression of Hsp25 becomes excluded from neural precursors
as well as other differentiating cells, making it a potentially useful marker of
early ES cell differentiation.
PMID- 17030444
TI - Diverse functions of p120ctn in tumors.
AB - p120ctn is a member of the Armadillo protein family. It stabilizes the cadherin
catenin adhesion complex at the plasma membrane, but also has additional roles in
the cytoplasm and nucleus. Extensive alternative mRNA splicing and multiple
phosphorylation sites generate additional complexity. Evidence is emerging that
complete loss, downregulation or mislocalization of p120ctn correlates with
progression of different types of human tumors. It remains to be determined
whether a causal relationship exists between specific isoform expression,
subcellular localization or selective phosphorylation of p120ctn on the one hand
and tumor prognosis on the other.
PMID- 17030445
TI - Formation of peroxisomes: present and past.
AB - Eukaryotic cells contain functionally distinct, membrane enclosed compartments
called organelles. Here we like to address two questions concerning this
architectural lay out. How did this membrane complexity arise during evolution
and how is this collection of organelles maintained in multiplying cells to
ensure that new cells retain a complete set of them. We will try to address these
questions with peroxisomes as a focal point of interest.
PMID- 17030446
TI - Elevated circulating oxidized LDL levels in Japanese subjects with the metabolic
syndrome.
AB - In the present study, we examined the relationship between circulating oxidized
low-density lipoprotein (LDL) and the metabolic syndrome in Japanese patients.
Subjects who had no histories of coronary or peripheral artery disease and were
taking no medications (n=119; age 57+/-10 years; male/female, 90:29) underwent a
complete history and physical examination, determination of blood chemistries and
oxidized LDL levels. In stepwise regression analysis, triglycerides (p=0.0001)
and HDL-cholesterol (p=0.0493, inversely) were independently correlated to
oxidized LDL levels. Furthermore, a significant association (p<0.0001) was found
between circulating oxidized LDL levels and the accumulation of the number of the
components of the metabolic syndrome. Oxidized LDL levels were one of the
independent determinants of intima-media thickness of the common carotid artery,
a surrogate marker of atherosclerosis. The present study reveals that circulating
oxidized LDL levels are strongly associated with the metabolic syndrome. Our
results suggest that elevation of oxidized LDL may be a possible molecular link
between accelerated atherosclerosis and the metabolic syndrome in Japanese
subjects.
PMID- 17030447
TI - Smoking expectancies for flavored and non-flavored cigarettes among college
students.
AB - Several tobacco companies have introduced specially flavored cigarettes, yet
little is known about their appeal among college student nonsmokers, regular
smokers, and those susceptible to smoking. Undergraduates (N=424) rated 12 brands
of cigarettes on multiple attributes based on manufacturer advertisements. This
paper focused on two brands with flavored and non-flavored versions (Camel and
Salem). Despite brand, regular smokers and those susceptible to smoking
initiation had higher positive expectancies and lower negative expectancies about
smoking than nonsmokers. Flavored cigarettes elicited higher positive
expectancies than non-flavored counterparts across all groups, including
nonsmokers. Indeed, the degree to which flavored Camels had higher positive
expectancies than Camel Lights was at least as large in a group of susceptible
nonsmokers and experimenters (susceptible/experimenters). Despite being present
in nonsmokers and susceptible/experimenters, negative expectancies were
significantly lower for flavored versus non-flavored brands. Logistic regressions
revealed that positive expectancies predicted "intention to try" each brand for
regular smokers and susceptible/experimenters. These findings suggest that
targeting the marketing of positive attributes may be useful in preventing
smoking behavior.
PMID- 17030449
TI - Inflammation in variant angina: is there any evidence?
AB - Variant angina, defined as spontaneous angina pectoris associated with transient
ST-segment elevation, has proved to be caused usually by episodic coronary spasm
since Prinzmetal and his associates described a form of angina quite different
from classic Heberden angina pectoris in 1959. Currently, coronary artery spasm
is defined as reversible coronary stenosis, which limits coronary blood flow
under resting conditions, and it plays an important role in ischemic heart
disease, particularly in variant angina. Data available in respect of coronary
vasospasm showed that it is closely related to atherosclerotic coronary artery
disease, since intravascular ultrasound studies reveal atherosclerotic plaques in
almost any spastic segment. Risk factors for coronary artery disease and coronary
vasospasm, however, differ profoundly. Cigarette smoking is the only established
risk factor. Although several candidates and predisposing factors, such as
serotonin, histamine, thromboxane, and endothelin, have been described, the
mediators and the pathogenesis of the disease remain unknown. There are abundant
studies that inflammation plays an important role in the initiation, development
as well as evolution of atherosclerosis, suggesting that atherosclerosis is an
inflammation disease. The evidence regarding the role of inflammatory pathways in
different clinical entities of coronary artery disease has significantly been
accumulated. And also, primary studies have showed that inflammation may be a
contributor for variant angina or vasospastic coronary disease is at least
partially driven by inflammation. Although much more research is obviously
needed, primary evidence provide us with some direction for that research.
PMID- 17030450
TI - A circadian model for viral persistence.
AB - Persistently infecting DNA viruses depend heavily on host cell DNA synthesis
machinery. Replication of cellular and viral DNA is inhibited by mutagenic
stress. It is hypothesized that diurnal regulation of viral DNA replication may
occur at the level of cell cycle checkpoints and DNA repair, to protect DNA from
exposure to UV light or other mutagens. This highly conserved mechanism is traced
back to viruses that persist in prokaryotes and eukaryotes. Inhibition of viral
DNA replication and the cell cycle in response to UV light may represent a
functional building block in the evolution of circadian-gated DNA replication.
Viral DNA replication appears to be closely linked to the circadian clock by
interaction of viral promoters, early viral proteins and transcription factors.
It is proposed here that under certain conditions viral oncogene expression is
phase-shifted relative to that of tumor suppressor and DNA repair genes. The
resulting desynchrony of checkpoint controls and DNA repair from diurnal
genotoxic exposure produces cyclic periods of suboptimal response to DNA damage.
This temporal vulnerability to genotoxic stress produces a "mutator phenotype"
with inherent genome instability. The proposed model delineates areas of research
with implications for viral pathogenesis and therapeutics.
PMID- 17030448
TI - The tyrosine kinase inhibitor genistein blocks HIV-1 infection in primary human
macrophages.
AB - Binding of HIV-1 envelope glycoprotein (Env) to its cellular receptors elicits a
variety of signaling events, including the activation of select tyrosine kinases.
To evaluate the potential role of such signaling, we examined the effects of the
tyrosine kinase inhibitor, genistein, on HIV-1 entry and infection of human
macrophages using a variety of assays. Without altering cell viability, cell
surface expression of CD4 and CCR5 or their abilities to interact with Env,
genistein inhibited infection of macrophages by reporter gene-encoding, beta
lactamase containing, or wild type virions, as well as Env-mediated cell-fusion.
The observation that genistein blocked virus infection if applied before, during
or immediately after the infection period, but not 24h later; coupled with a more
pronounced inhibition of infection in the reporter gene assays as compared to
both beta-lactamase and p24 particle entry assays, imply that genistein exerts
its inhibitory effects on both entry and early post-entry steps. These findings
suggest that other exploitable targets, or steps, of the HIV-1 infection process
may exist and could serve as additional opportunities for the development of new
therapeutics.
PMID- 17030451
TI - Outbreak of hepatitis C virus infection during sclerotherapy of varicose veins:
long-term follow-up of 196 patients (4535 patient-years).
AB - BACKGROUND/AIMS: The aim of this study was to describe the natural history of a
HCV infection outbreak in 196 patients who had sclerotherapy by a same physician
and to confirm patient-to-patient transmission using phylogenetic analysis in a
large series of patients. METHODS: Demographic information included clinical and
biological parameters. Fibrosis evaluation was performed using liver biopsy or
transient elastography. Follow-up was maintained until death, or the end of the
observation period. In order to determine if the virus had been transmitted
between the HCV genotype 2 patients, sequence analysis was undertaken of a part
of the NS5b region of the genomes in samples of patients. RESULTS: The mean
duration of follow-up was 23.1+/-6.7 years (4535 patient-years). In patients with
fibrosis evaluation, 55.7% had no or mild fibrosis and 44.3% had significant
fibrosis. No patient died from HCV-related disease. Nucleotide sequence analysis
of a part of the NS5b region revealed that patients were all infected with the
same HCV subtype (genotype 2d). The most evident feature of the tree is the
clustering of all patients involved in the outbreak without any unrelated
isolates. CONCLUSION: This study emphasizes the risk for nosocomial spread of HCV
during intravenous therapy.
PMID- 17030452
TI - Thalidomide prevents rat liver cirrhosis via inhibition of oxidative stress.
AB - This study investigated the effect of thalidomide on oxidative stress in rat
liver cirrhosis. The cirrhosis of rat was induced by intraperitoneal injection of
carbon tetrachloride thrice weekly; meanwhile, thalidomide (10mg/kg or 100mg/kg)
was given daily by intragastric administration for 8 weeks. The content of
oxidative stress parameters, including superoxide dismutase, glutathione
peroxidase, and malondialdehyde, in the liver was detected by biochemical assay.
Immunohistochemistry revealed alpha-smooth muscle actin (alpha-SMA), desmin, and
tissue inhibitor of metalloproteinase-1 (TIMP-1) protein in the liver. Nuclear
factor kappa B p65 (NF-kappaBp65) protein in nucleus and transforming growth
factor beta1 (TGF-beta1) protein in cytoplasm were detected by Western blot. NF
kappaBp65, TGF-beta1, and TIMP-1 mRNA levels in the liver were studied using
reverse transcriptase polymerase chain reaction. Liver histopathology was
significantly improved in rats given high doses of thalidomide. The content of
oxidative stress parameters and the expressions of NF-kappaBp65, TGF-beta1 and
TIMP-1 protein, and mRNA were significantly decreased in these animals. The
expressions of alpha-SMA and Desmin protein were also significantly decreased in
them. Thalidomide might exert an effect on the inhibition of oxidative stress via
downregulation of NF-kappaB signaling pathway to prevent the progression of liver
cirrhosis.
PMID- 17030453
TI - [Nosocomial respiratory infection due to an imipenem-resistant Pseudomonas
aeruginosa O: 12 strain in a Tunis's neonatal intensive care unit].
AB - OBJECTIVE: Investigation of an outbreak caused by an imipenem-resistant
Pseudomonas aeruginosa strain and research of its hospital reservoir. PATIENTS
AND METHODS: Nine strains isolated from protected tracheal specimens during 14
weeks (October 2004 to January 2005) from 8 infants, and one strain from vacuum
interrupter were studied. Epidemiological study was investigated by determination
of antibiotics susceptibility, serotyping and Pulsed-field gel electrophoresis
(PFGE). RESULTS: Strains were of O:12 serotype, they have the same antibiotype
characterised by imipenem resistance. Strains were indistinguishable or closely
related as determined by PFGE. The common source of P. aeruginosa O:12 strains
was not determined, however eradication of the epidemic strain was obtained by
amelioration of hygiene conditions and the change of disinfectors. CONCLUSION:
Outbreak of respiratory infections due to an imipenem-resistant P. aeruginosa
O:12. The common source of the epidemic strain was not determined.
PMID- 17030454
TI - Genotype MRSA, a new genetic test for the rapid identification of staphylococci
and detection of mecA gene.
AB - Early detection of Staphylococcus methicillin resistance (MR) is essential.
However MR determination may be difficult because it is necessary to perform
investigation of heterogeneous resistance and low level of resistance and to
discriminate between oxacillin resistance and borderline resistance. Several
phenotypic methods are recommended but they fail to detect low level of
production de PBP2a, the modified Penicillin Binding Protein responsible for MR.
Detection of mecA gene, the gene encoding PBP2a, using PCR is considered to be
the reference method. We evaluated Genotype MRSA, a new rapid system based on DNA
multiplex amplification and further hybridisation, for the identification of
staphylococci and detection of the mecA gene. The study was performed on a
collection of various Staphylococcus strains (N=30) from clinical human isolates
including S. aureus MR and methicillin susceptible (MS), S. epidermidis MR and
MS, and other species of coagulase negative Staphylococcus (CNS) MR and MS. For
all the strains, the hybridization banding pattern obtained using Genotype MRSA
correlated with their expected phenotypic and genotypic characteristics. Genotype
MRSA allows the identification of the mecA gene as well as S. aureus and S.
epidermidis specific genes. This DNA strip technology based assay can easily be
incorporated into routine diagnostics. In addition, the short testing time (less
than 2 hours) optimises treatment orientation. Genotype MRSA completely complies
with all requirements for a fast, safe, valid and cost-effective MR diagnosis in
staphylococci.
PMID- 17030455
TI - [Mycoplasma pneumoniae infections: retrospective study in Basse-Normandie, 1997
2005. Epidemiology--diagnostic utility of serology and PCR for a rapid
diagnostic].
AB - OBJECTIVES: The objective of this study was to evaluate the epidemiology of
Mycoplasma pneumoniae (Mpn) infections in Basse-Normandie by a retrospective
analysis of serological and PCR data, and to confirm the diagnostic utility of
PCR and serology. METHODS: From 1997 to August 2005, 6156 serum samples and 6123
respiratory tract samples were collected from hospitalised patients and evaluated
for the diagnosis of Mpn infection by PCR, serological assays, or by the two
tests. During the epidemic period (2004-2005), the results of 1489 patients were
analysed. RESULTS: Over the 9-y period, the seroprevalence was 40,4% and we
reported on 525 cases with serologically or/and PCR proven Mpn infection,
according a cyclic pattern spaced out 7 years. During the epidemic period, the
seroprevalence increased to 50,2% and the rate of infections was 8.3%. The
analysis of the 124 cases of Mpn infection showed typical epidemiological
characteristics: a peak of incidence among the children and young adults, a
summer-winter pattern and some coinfections with viral strains. For diagnosis of
Mpn infection, the comparison of PCR and serological assays among 36 patients
showed a concordance of only 41.7%. CONCLUSION: Mpn infections were endemic and
outbreaks were observed according cyclic pattern with a high incidence specially
in the children. Sensitive and specific tests were now available for early and
reliable diagnosis. In children, the combination of the PCR on nasopharyngeal
samples and the IgM EIA serology test were recommended. In adults, the PCR was
privilegiated.
PMID- 17030456
TI - [Antimicrobial susceptibility of Proteus mirabilis urinary tract isolates from
1999 to 2005 at Nimes University Hospital].
AB - AIM OF THE STUDY: To analyse antimicrobial resistance trends of Proteus mirabilis
urinary tract isolates from 1999 to 2005 at the Nimes University hospital.
MATERIALS AND METHODS: We retrospectively collected non-duplicate urinary tract
infections and colonization isolates from inpatients between 1 January 1999 and
31 December 2005. RESULTS: One thousand and eight non-duplicate urinary tract
isolates were studied, 63.1% were from females and the mean age was 76 years. The
mean resistance rate was 59.0% for amoxicillin (AMX), 48.0% for piperacillin
(PIP), 3.9% for cefotaxim, 33.9% for amoxicillin plus clavulanic acid (AMC) and
2.8% for piperacillin plus tazobactam (TZP). A significant increase in resistance
was observed for AMC and TZP. The mean resistance rate was 35.0% for norfloxacin,
34.8% for ofloxacin and 23.5% for ciprofloxacin. No significant increase in
resistance to fluoroquinolones was seen except for ciprofloxacin whereas a
significant increase was observed for aminoglycosides. The mean rate resistance
for cotrimoxazole was 33.2% with a significant decrease in the resistance during
the study period. CONCLUSION: P. mirabilis stilled sensitive to cefotaxim or
ceftazidim and to TZP. The significant increase in the rate resistance to AMC and
TZP could be explained by production of beta-lactamases and in particular
extended-spectrum beta-lactamases. The increase in resistance observed for
fluoroquinolones become a major concern. Amikacine was the most active
aminoglycosides. These data suggested for the re-enforcement of the antimicrobial
susceptibility surveillance in order to optimise the rational use of antibiotics.
PMID- 17030457
TI - [Early detection of hepatitis C virus infection using a new combined antigen
antibody detection assay: potential use in HIV co-infected individuals].
AB - BACKGROUND: The aim of this study was to determine the clinical benefit of a new
combined antigen-antibody immunoenzymatic assay (Monolisa HCV Ag-Ab Ultra,
Biorad) in the setting of acute HCV infection in HIV infected patients. PATIENTS
AND METHODS: The performance of this assay was first evaluated in 160 HIV
positive samples from uninfected and chronically HCV infected patients. To assess
the performance of the Ag-Ab assay in the context of acute hepatitis C, 94 stored
frozen serums from 20 recently diagnosed cases were retrospectively tested for
HCV-RNA and presence of anti-HCV antibodies, in parallel with the new assay.
RESULTS: In HIV infected patients, the sensitivity and specificity of the Ultra
assay was 100% with a strong discrimination between positive and negative
samples. In HCV acutely infected patients, the Ag-Ab assay significantly reduced
the seronegative period, allowing an earlier diagnosis compared to a 3rd
generation ELISA in 65% of the cases. The combined assay became positive on the
same bleed as the first HCV-RNA detection for 13 patients out of 20.
Nevertheless, in one case, characterized by an absence of seroconversion over one
year but a continuous viral replication above 1 million IU/ml, the combined assay
did not improve HCV infection diagnosis. CONCLUSION: Use of this new assay as a
first line screening would significantly reduce the long seronegative window
period seen in HCV infection allowing earlier HCV diagnosis and rapid clinical
management. However, in case of clinical acute hepatitis C, sensitive HCV-RNA
detection should remain the gold standard.
PMID- 17030458
TI - [Extended-spectrum betalactamases producing Escherichia coli: a new health-care
associated infection threat?].
AB - OBJECTIVES: Study the health-care associated infection risk due to Extended
Spectrum Betalactamases Producing Escherichia coli (ESBL Esc) isolated from
diagnostic samples. METHODS: Descriptive, longitudinal and prospective study of
104 diagnostic isolates of ESBL Esc, one per patient, identified in Amiens
university hospital between February 1999 and December 2005. Patients (sex, age,
contamination risk factor, antecedent hospitalization) and microbiological data
were progressively collected, entered into EPI INFO 6.04dFr software (ENSP,
France) database, and compared using the chi-square test and Wilcoxon rank sum
test, as appropriate. A p value of less than 0.05 was considered significant.
RESULTS: Diagnostic ESBL Esc isolates raised, per 1000 isolates of Esc, from 1.2
in 1999 to 6 in 2005. Global and acquired isolates number of ESBL Esc varied from
7 and 3 in 2002 to 25 and 19 in 2003 (P=0.22). ESBL Esc global and acquired
incidence per 10(5) patient-days were, 0.8 and 0.6 in 1999 and 4.99 and 3.4 in
2005 (P<10(-6)), but rose from 0.6 acquired isolate in 2002 to 3.9 in 2003
(P=0.002). ESBL Esc, isolated from urines, stools, pulmonary, blood and surgical
site samples of patients of>/=65 years aged (68.3%), were imipenem and latamoxef
sensitive. Their acquisition risk factors found were hospitalization during the
last 6 month period (40/104) and transfer from other institutions (20/104).
CONCLUSION: ESBL Esc isolates, among ESBL-producing Enterobacteriaceae,
constitute an escalating health-care associated risk in our institution. The
research at admission time of ESBL-producing Enterobacteriaceae, mainly in acute
geriatric wards, strict isolation precaution and hand hygiene observance,
rational antibiotic usage, are the key actions to control their cross
transmission. Nonetheless, other studies are needed to determine whether we are
in front of an ESBL Esc new clone emergence.
PMID- 17030460
TI - Bacterial aetiology of diarrhoea in young children: high prevalence of
enteropathogenic Escherichia coli (EPEC) not belonging to the classical EPEC
serogroups.
AB - Diarrhoeal disease continues to be one of the most common causes of admittance in
Children hospital emergency. The aim of the present study was to investigate the
relative contribution of enteropathogenic and enterohemorrhagic Escherichia coli
(EPEC and EHEC, respectively) as a cause of infectious bacterial diarrhoea in
children from the region of Toulouse. We analysed 280 samples of stools from 280
children (<2 years) with diarrhoea admitted in the "Hopital des Enfants" from
January to August 2005. Classic pathogens (Salmonella, Campylobacter, Yersinia,
Shigella, Aeromonas and Vibrio) were detected by standard culture methods.
Enterotoxigenic Clostridium difficile were identified after culture by immuno
enzyme assay (IEA). Virulence genes of EPEC and EHEC were detected by using PCR.
Shiga-toxin production of EHEC strains was confirmed with an IEA test. Potential
enteric pathogens were identified in 55 patients. EPEC was the most frequently
identified agent (30 patients), followed by Campylobacter (9 cases: 7 C. jejuni
and 2 C. coli) and C. difficile (8 patients), then EHEC (5 patients) and
Salmonella (3 patients). No Shigella, Yersinia, Aeromonas or other pathogenic
bacteria were detected during this period in that class of children. EPEC not
belonging to the classical EPEC serogroups were highly prevalent (24 versus 6).
EHEC possessed different genotypes and serogroups: O26 (2 strains), O157 (2
strains) and one un-typable strain. This study demonstrates the importance of
EPEC (55 % of positive cases) and of EHEC (more frequent than Salmonella) in the
aetiology of diarrhoeal diseases of young children. We confirm the usefulness of
the PCR methodology: it allows the detection of virulent E. coli and thus
increases by two fold the diagnosis of bacterial diarrhoea.
PMID- 17030459
TI - [Performance of different methods of oxacillin resistance detection in atypic
strains of Staphylococcus aureus].
AB - Seventy-three of aminoglycoside-susceptible methicillin-resistant Staphylococcus
aureus (AS-MRSA) and 12 kanamycin-tobramycin-resistant methicillin-susceptible S.
aureus (KTR-MSSA) isolates were phenotypically and genotypically examined for
methicillin susceptibility. The AS-MRSA profile represents 8.3% of MRSA strains
and the KTR-MSSA profile represents 1.38% of MSSA strains. The diffusion method
using the 5 microg oxacillin and 30 microg cefoxitin discs on Mueller-Hinton Agar
(MHA) with and without NaCl, the incubation at 35 degrees C or 30 degrees C for
24 or 48 hours respectively, and the determining oxacillin MICs by E-test (AES,
Combourg, France) were performed and used as phenotypic methods. We also used the
mecA gene PCR which was considered as the "gold standard" for methicillin
resistance detection, and the Slidex MRSA Detection (bioMerieux) that detect the
presence of mecA gene product (PBP 2a). To increase the level of PBP 2a
expression, the 30 microg cefoxitin disc was used as an inducer. All the AS-MRSA
strains (100%) were detected by the cefoxitin disc in all conditions and by the
oxacillin disc on MHA with 2% of NaCl at 35 degrees C. Without NaCl, the
sensitivity fell to 97,2% by oxacillin disc. The oxacillin MICs for these
isolates ranged from 2 to 128 mg/l. The mecA gene determinant and its product PBP
2a were detected in all AS-MRSA strains. All KTR-MSSA strains were phenotypically
methicillin-susceptible and oxacillin MICs were below or borderline of breakpoint
(< or =2 mg/l). The mecA gene determinant and its product were detected in one
strain which was considered to be the most heterogeneous of those tested.
PMID- 17030461
TI - Carbonic anhydrase IX expression is associated with tumor progression and a poor
prognosis of lung adenocarcinoma.
AB - Carbonic anhydrase (CA) IX catalyzes the hydration of carbon dioxide into
carbonic acid and participates in a variety of physiological and biological
processes. The aim of this study was to evaluate the prognostic significance of
CA IX expression in patients with lung adenocarcinoma. Standard
immunohistochemical techniques were used to study CA IX expression in 134
patients who underwent curative resection for adenocarcinoma of the lung at our
hospital between January 1995 and December 1996. We evaluated the correlations
between CA IX expression levels on cancer cells and clinicopathological factors.
CA IX expression was not observed in normal lung tissue or specimens from non
invasive adenocarcinomas. CA IX immunostaining was detected in 33 (24.6%)
invasive adenocarcinoma cases. Poor differentiated histological phenotype
(p=0.0015), pathological stage (p=0.0400), vascular invasion (p=0.0009) and
lymphatic permeation (p=0.0050) were significantly related to CA IX expression.
On univariate analysis, CA IX positive cases showed significantly shorter overall
survival (p=0.0083) and disease-free survival (p=0.0122). In particular, the
overall and disease-free survivals in stages I+II were significantly shorter in
the CA IX positive than in the CA IX negative cases (p=0.0269 and 0.0011,
respectively). Our results suggest that CA IX expression is strongly associated
with tumor progression and indicates a poor prognosis for patients with stages
I+II lung adenocarcinoma.
PMID- 17030462
TI - DNA methylation in reptiles.
AB - Very recent investigations have provided evidence for a higher DNA methylation
level in polar and sub-antarctic fishes compared to temperate/tropical fishes,
the latter being in turn higher than the DNA methylation level of warm-blooded
vertebrates. These results confirm and extend the finding [Jabbari, K., Caccio,
S., Pais de Barros, J.P., Desgres, J., Bernardi G., 1997. Evolutionary changes in
CpG and methylation levels in the genome of vertebrates. Gene 205, 109-118] that
DNA methylation level of vertebrates is inversely related to body temperature.
Here we studied the methylation level of reptilian genomes. The species
previously analyzed exhibited methylation levels closer to those of mammals and
birds rather than to those of fishes and amphibians. The sample was, however, too
small to reach a final conclusion. Here we used Reversed-Phase-High-Performance
Liquid Chromatography (RP-HPLC) to analyze the DNA methylation levels of 43
reptiles representing three out of four orders and 20 families. Such analysis has
shown that snakes and lizards exhibit methylation levels covering the whole range
comprised between those of temperate/tropical fish and mammals, while turtles,
and, more so, crocodiles are close to mammals. We discuss some ecological and
physiological data that explain these results.
PMID- 17030463
TI - Transport of sulfadiazine in soil columns: experiments and modelling approaches.
AB - Antibiotics, such as sulfadiazine, reach agricultural soils directly through
manure of grazing livestock or indirectly through the spreading of manure or
sewage sludge on the field. Knowledge about the fate of antibiotics in soils is
crucial for assessing the environmental risk of these compounds, including
possible transport to the groundwater. Transport of (14)C-labelled sulfadiazine
was investigated in disturbed soil columns at a constant flow rate of 0.26 cm h(
1) near saturation. Sulfadiazine was applied in different concentrations for
either a short or a long pulse duration. Breakthrough curves of sulfadiazine and
the non-reactive tracer chloride were measured. At the end of the leaching period
the soil concentration profiles were determined. The peak maxima of the
breakthrough curves were delayed by a factor of 2 to 5 compared to chloride and
the decreasing limbs are characterized by an extended tailing. However, the
maximum relative concentrations differed as well as the eluted mass fractions,
ranging from 18 to 83% after 500 h of leaching. To identify relevant sorption
processes, breakthrough curves of sulfadiazine were fitted with a convective
dispersive transport model, considering different sorption concepts with one, two
and three sorption sites. Breakthrough curves can be fitted best with a three
site sorption model, which includes two reversible kinetic and one irreversible
sorption site. However, the simulated soil concentration profiles did not match
the observations for all of the used models. Despite this incomplete process
description, the obtained results have implications for the transport behavior of
sulfadiazine in the field. Its leaching may be enhanced if it is frequently
applied at higher concentrations.
PMID- 17030464
TI - Detection of Helicobacter spp. DNA in the oral cavity of dogs.
AB - The mode of acquisition of gastric Helicobacter spp. infection in dogs has not
been determined. It is suspected that oral-oral and faecal-oral transmission may
be involved. The present study sought to determine if Helicobacter spp. DNA is
present in the oral cavity of healthy and vomiting dogs. Thirty-eight pet dogs
(27 vomiting and 11 clinically healthy) were studied. The presence of
Helicobacter spp. was determined by single and nested PCR evaluation of DNA
extracted from saliva, dental plaque and gastric biopsy samples. Helicobacter
spp. DNA was detected by nested PCR in 36 (94.7%) gastric biopsies, 17 (44.7%)
dental plaque and 19 (50%) saliva samples out of the 38 dogs examined. Overall 27
(71.1%) dogs screened by nested PCR were found to harbour Helicobacter spp. DNA
in the oral cavity (dental plaque and/or saliva). There was no significant
difference in the prevalence of Helicobacter spp. DNA in the oral cavity of
vomiting and healthy dogs, and the time from vomiting to oral sampling did not
have significant impact. This study confirms the high prevalence of gastric
Helicobacter spp. infection in dogs, and reveals that Helicobacter spp. DNA is
detectable in the oral cavity of over 70% of dogs. These findings support the
possibility of oral-oral transmission between dogs and that the canine oral
cavity may act as source of non-pylori Helicobacter spp. infection for humans.
PMID- 17030465
TI - Bradykinin release and inactivation in brain of rats submitted to an experimental
model of Alzheimer's disease.
AB - The kallikrein-kinin system is involved in a variety of physiological and
pathological processes. Components of this system, identified in rat and human
brains, can be altered in neurodegenerative processes such as Alzheimer's
disease. Here, we studied kinin release and its inactivation in rats submitted to
chronic cerebroventricular infusion of beta-amyloid (Abeta) peptide.
Neurodegeneration was confirmed by histological analysis of brain samples. In
cerebrospinal fluid of animals infused with Abeta, bradykinin concentration was
increased, as determined by radioimmunoassay. However, in the brain of Abeta
group, we only detected the tripeptide Arg-Pro-Pro, purified by reversed-phase
chromatography and characterized by liquid chromatography-electrospray ionization
mass spectrometry. This fragment of bradykinin indicated the possible
participation of kinin-processing enzymes in the brain such as a prolyl
oligopeptidase.
PMID- 17030466
TI - Toxicokinetics of 1,1,1,2-tetrafluoroethane (HFC-134a) in male volunteers after
experimental exposure.
AB - The aim of this study was to determine the uptake and disposition of inhaled
1,1,1,2-tetrafluoroethane (HFC-134a) in humans. Ten male volunteers were exposed
to 500 ppm HFC-134a (2 h, 50 W exercise). The HFC-134a levels were monitored in
blood, exhaled air and urine up to 19 h post-exposure. The concentration in blood
increased rapidly, reaching a plateau of 9.4+/-1.9 microM (mean+/-S.D.) within 30
min, followed by a fast post-exposure decrease. HFC-134a in expired air decreased
rapidly as well and in parallel with that in blood. The post-exposure urinary
excretion was 0.002% of the inhaled amount, and the half-time was 58 min (pooled
data). A physiologically based toxicokinetic (PBTK) model was developed for
further analysis. Experimental and simulated time courses in blood and exhaled
air agreed well in all 10 subjects. Further, the late decay in blood was
consistent with a wash-out of HFC-134a from fat tissues, with a half-time of
114+/-21 min. The simulated relative uptake during exposure was 3.7+/-0.5%. No
remarkable findings were observed in the electrocardiographic recordings.
Fibrinogen in plasma increased 1 day after exposure, whereas no effects on C
reactive protein, serum amyloid A protein, D-dimer or uric acid were seen.
Further studies are needed to investigate the possible inflammatory response.
PMID- 17030467
TI - Impact of menopause and hormonal replacement therapy on harmonics-to-noise-ratio
of the voice.
PMID- 17030469
TI - Cloning, molecular characterization and expression of ecto-nucleoside
triphosphate diphosphohydrolase-1 from Torpedo electric organ.
AB - During synaptic transmission large amounts of ATP are released from pre- and post
synaptic sources of Torpedo electric organ. A chain reaction sequentially
hydrolyses ATP to adenosine, which inhibits acetylcholine secretion. The first
enzyme implicated in this extracellular ATP hydrolysis is an ecto-nucleoside
triphosphate diphosphohydrolase (E-NTPDase) that dephosphorylates both ATP and
ADP to AMP. This enzyme has been biochemically characterized in the synaptosomal
fraction of Torpedo electric organ, having almost equal affinity for ATP as for
ADP, a fact that pointed to the type-1 NTPDase enzyme. In the present work we
describe the cloning and molecular characterization of the cDNA for an NTPDase
from Torpedo marmorata electric organ. The clone, obtained using the RACE-PCR
technique, contains and open-reading frame of 1506bp and encodes a 502 amino
acids protein that exhibits high homology with other NTPDases1 from vertebrates
previously identified, including those of zebrafish and Xenopus, as well as
human, rat and mouse. Topology analyses revealed the existence of two
transmembrane regions, two short cytoplasmic tails and a long extracellular
domain containing five apyrase-conserved regions. Gene expression studies
revealed that this gene is expressed in all the Torpedo tissues analyzed.
Finally, activity and cellular localization of the protein encoded by this newly
cloned cDNA was assessed by heterologous expression experiments involving COS-7
and HeLa cells.
PMID- 17030470
TI - Low density porous carrier drug adsorption and release study by response surface
methodology using different solvents.
AB - Low density porous carriers are widely used in the pharmaceutical applications.
Response surface methodology, using 3(2) factorial design was used to study drug
adsorption on and its release patterns from microporous polypropylene (Accurel MP
1000) in the absence of additives. Ibuprofen, as model drug, was adsorbed on the
polymer by solvent evaporation using two organic solvents methanol (M) and
dichloromethane (DCM). The amount of carrier (100 mg) and its particle size range
(250-350 microm) were kept invariant while solvent volume (X1) and drug amount
(X2) were taken as variables. Drug adsorption pattern depended on the type and
amount of solvent used. DSC, XRD, FTIR and TGA, predict crystalline nature and
physical form of adsorption. SEM showed the penetration and adsorption of the
drug in and on the microporous polymer. Accurel MP 1000 had a pore volume of
1.992 g/cm3 and surface area of 55.9855 m2/g as detected by mercury porosimetery.
On drug adsorption, pore volume ranged from 0.413 to 1.198 g/cm3 for methanol and
0.280-0.759 g/cm3 for DCM. Similarly surface area was in the range 38.445-25.497
m2/g for methanol and 18.710-32.528m2/g for DCM. The drug release was
investigated in phosphate buffer pH 7.2. All batches showed excellent in vitro
floating property. Drug release was partial with recovery to complete dependent
on type and volume of solvent. R2 values relating to bulk density, pore volume,
surface area and drug release at 60, 120 and 180 min were estimated. Effect of
solvent properties shows a positive influence on drug adsorption and release.
Release profiles of some batches could be considered as gastroretentive drug
delivery system.
PMID- 17030472
TI - Hippocampal volumes are larger in postmenopausal women using estrogen therapy
compared to past users, never users and men: a possible window of opportunity
effect.
AB - Considerable evidence suggests that estrogen can have neuroprotective effects.
However, recent results raised important questions regarding the conditions under
which hormone therapy (HT) following menopause can be beneficial. It has been
suggested that variables such as time of initiation and duration of HT use are of
critical importance for beneficial cognitive effects to be observed. The aim of
the present study was to investigate the potential neuroprotective effects of
estrogens in aging on brain regions with high levels of estrogen receptors,
namely the hippocampus (HC) and the amygdala (AG). In order to better
characterize the punctual and long-term effects of estrogens, we tested
postmenopausal women currently using estrogen therapy alone (ET), past HT users,
never users, and men. Age at menses, age at menopause, HT duration and age were
included as covariates in the analysis. Results demonstrate that women using ET
had larger left and right HC volumes compared to men, and larger right HC volumes
compared to past users and never users. Importantly, we found a significant
negative relationship between ET duration and HC volume in this group. The
observed effects were region-specific since no significant differences could be
observed for the AG. In summary, these findings support a treatment duration
dependent neuroprotective role of estrogen on HC volume in aging.
PMID- 17030473
TI - Spine tingling polymorphisms--is apolipoprotein E involved in dendritic shape and
plasticity?
PMID- 17030474
TI - Loss of spastic paraplegia gene atlastin induces age-dependent death of
dopaminergic neurons in Drosophila.
AB - Hereditary spastic paraplegias (HSPs) are human genetic disorders causing
increased stiffness and overactive muscle reflexes in the lower extremities.
atlastin (atl) is one of the major genes in which mutations result in HSP. We
generated a Drosophila model of HSP that has a null mutation in atl. As they
aged, atl null flies were paralyzed by mechanical shock such as bumping or
vortexing. Furthermore, the flies showed age-dependent degeneration of
dopaminergic neurons. These phenotypes were rescued by targeted expression of atl
in dopaminergic neurons or feeding L-DOPA or SK&F 38393, an agonist of dopamine
receptor. Our data raised the possibility that one of the causes of HSP disease
symptoms in human patients with alt mutations is malfunction or degeneration of
dopaminergic neurons.
PMID- 17030475
TI - Preliminary evidence that long-term estrogen use reduces white matter loss in
aging.
AB - Despite numerous studies showing neurotrophic and neuroprotective effects of
estrogen in animal models, the long-term effects of estrogen use on brain
morphology in older women are not known. Thus, we compared ventricular,
cerebrospinal fluid, white matter, and grey matter volumes estimated from
magnetic resonance images of postmenopausal women with more than 20 years
exposure to unopposed estrogen, women who were not on estrogen, and young healthy
women. Estrogen users had significantly smaller ventricles and greater white
matter volumes than non-users, but hormone exposure did not affect grey matter
volumes. Young healthy women had significantly smaller ventricles, less
cerebrospinal fluid and more grey matter than both groups of older women.
However, they had comparable white matter volumes to older women on estrogen.
These findings suggest that long-term estrogen protects against white matter loss
in aging. This adds to findings from other studies suggesting estrogen is
neuroprotective of the hippocampus and other regions in older women.
PMID- 17030476
TI - Ebselen treatment reduces noise induced hearing loss via the mimicry and
induction of glutathione peroxidase.
AB - Previous studies indicate that noise induced hearing loss (NIHL) involves a
decrease in glutathione peroxidase (GPx) activity and a subsequent loss of outer
hair cells (OHC). However, the cellular localization of this GPx decrease and the
link to OHC loss are still poorly understood. In this report, we examined the
cellular localization of GPx (GPx1, GPx 3 and GPx 4) in F-344 rat before and
after noise exposure and after oral treatment with ebselen, a small molecule
mimic of GPx activity. Results indicate that GPx1 is the major isoform within the
cochlea and is highly expressed in cells of the organ of Corti, spiral ganglia,
stria vascularis, and spiral ligament. Within 5h of noise exposure (4h at 113 dB,
4-16 kHz), significant OHC loss was already apparent in regions coincident with
the 8-16 kHz region of the cochlea. In addition, the stria vascularis exhibited
significant edema or swelling and a decrease in GPx1 immunoreactivity or
fluorescent intensity. Treatment with ebselen (4 mg/kg p.o.) before and
immediately after noise exposure reduced both OHC loss and the swelling of the
stria vascularis typically observed within 5h post-noise exposure. Interestingly,
GPx1 levels increased in the stria vascularis after noise and ebselen treatment
vs noise and vehicle-only treatment, and exceeded baseline no noise control
levels. These data indicate that ebselen acts to prevent the acute loss of OHCs
and reduces the acute swelling of the stria vascularis by two potential
mechanisms: one, as a ROS/RNS scavenger through its intrinsic GPx activity, and
two, as a stimulator of GPx1 expression or activity. This latter mechanism may be
due to the preservation of endogenous GPx1 from ROS/RNS induced degradation
and/or the stimulation of GPx1 expression or activity.
PMID- 17030477
TI - Frequency discrimination of complex tones by hearing-impaired subjects: Evidence
for loss of ability to use temporal fine structure.
AB - For normally hearing subjects, thresholds for discriminating the fundamental
frequency (F0) of a complex tone, F0DLs, increase when the number of the lowest
harmonic, N, is above eight. A previous study showed that F0DLs were affected by
component phase for N above 7, and it was argued that the increase in F0DLs with
increasing N reflects a loss of temporal fine structure information. Here,
subjects with moderate hearing loss were tested in a similar experiment. F0DLs
were measured for tones with three successive harmonics, added in cosine or
alternating phase. The center frequency was 2000 Hz. N was varied by changing the
mean F0. A background noise was used to mask combination tones. F0 was roved
across trials and N was roved by +/-1, to reduce use of excitation pattern cues.
F0DLs were smaller for cosine than for alternating phase for four out of six
subjects, and this occurred once N exceeded 5. In contrast to the result for
normally hearing subjects, F0DLs decreased with increasing N. Performance was
much worse than obtained for normally hearing subjects at the same center
frequency, suggesting that most of the hearing-impaired subjects had a poor
ability to use temporal fine structure information.
PMID- 17030478
TI - Brazilian plants as possible adaptogens: an ethnopharmacological survey of books
edited in Brazil.
AB - In a survey, from Brazilian books, we searched plants that are in popular use for
purposes resembling those of an adaptogen. This study focused on 24 books by
authors from diverse regions in the country, resulting in a total of 1317
citations of uses related to a possible adaptogen effect from approximately 766
plants. Only species native to Brazil, cited in at least four books, were
selected, resulting a total of 33 species, belonging to 24 families. Of these,
four species have been studied previously in relation to effects that are
considered as part of an adaptogen effect (anti-stress, memory enhancement,
increased physical and/or sexual performance): Heteropterys aphrodisiaca
(Malpighiaceae), Paullinia cupana (Sapindaceae), Ptychopetalum olacoides
(Olacaceae), and Turnera diffusa (Turneraceae). Three others--Pfaffia glomerata,
Pfaffia paniculata (Amaranthaceae), and Trichilia catigua (Meliaceae)--have also
been the object of pharmacological studies that support their use as a possible
adaptogen, but they are listed in less than four books. The overall results
obtained in the present review of Brazilian folk literature reveals that Brazil
is rich in plants with potential adaptogen-like effect, but lacks pharmacological
studies (mostly clinical ones) to confirm these therapeutic properties.
PMID- 17030479
TI - Stimulative effects of Ulmus davidiana Planch (Ulmaceae) on osteoblastic MC3T3-E1
cells.
AB - Ulmus davidiana Planch (Ulmaceae) has long been known to have anti-inflammatory
and protective effects on damaged tissue, inflammation and bone among other
functions. To treat rheumatoid arthritis (RA), a herbal medicine, Ulmus davidiana
Planch (Ulmaceae) extract (UD) is being used in traditional oriental medicine.
The effect of UD on the proliferation and osteoblastic differentiation in non
transformed osteoblastic cells (MC3T3-E1) was studied. UD dose-dependently
increased DNA synthesis (significant at 5-20 microg/ml). UD increased alkaline
phosphatase (ALP) activity and prolyl hydroxylase activity of MC3T3-E1 cells (5
20 microg/ml). Antiestrogen tamoxifen eliminated the stimulation of proliferation
and ALP activity of MC3T3-E1, which was induced by UD. UD at concentrations
ranged from 30 to 100 microg/ml inhibited prostaglandin E2 production in MC3T3
E1. These results indicate that UD directly stimulates cell proliferation and
differentiation of osteoblasts. These results also suggest and UD is effective
for bone anti-resorptive action in bone cells.
PMID- 17030480
TI - Medicinal smokes.
AB - All through time, humans have used smoke of medicinal plants to cure illness. To
the best of our knowledge, the ethnopharmacological aspects of natural products'
smoke for therapy and health care have not been studied. Mono- and multi
ingredient herbal and non-herbal remedies administered as smoke from 50 countries
across the 5 continents are reviewed. Most of the 265 plant species of mono
ingredient remedies studied belong to Asteraceae (10.6%), followed by Solanaceae
(10.2%), Fabaceae (9.8%) and Apiaceae (5.3%). The most frequent medical
indications for medicinal smoke are pulmonary (23.5%), neurological (21.8%) and
dermatological (8.1%). Other uses of smoke are not exactly medical but beneficial
to health, and include smoke as a preservative or a repellent and the social use
of smoke. The three main methods for administering smoke are inhalation, which
accounts for 71.5% of the indications; smoke directed at a specific organ or body
part, which accounts for 24.5%; ambient smoke (passive smoking), which makes up
the remaining 4.0%. Whereas inhalation is typically used in the treatment of
pulmonary and neurological disorders and directed smoke in localized situations,
such as dermatological and genito-urinary disorders, ambient smoke is not
directed at the body at all but used as an air purifier. The advantages of smoke
based remedies are rapid delivery to the brain, more efficient absorption by the
body and lower costs of production. This review highlights the fact that not
enough is known about medicinal smoke and that a lot of natural products have
potential for use as medicine in the smoke form. Furthermore, this review argues
in favor of medicinal smoke extended use in modern medicine as a form of drug
delivery and as a promising source of new active natural ingredients.
PMID- 17030481
TI - Quantitative structure-activity relationship studies of HIV-1 integrase
inhibition. 1. GETAWAY descriptors.
AB - The GEometry, Topology, and Atom-Weights AssemblY (GETAWAY) approach has been
applied to the study of the HIV-1 integrase inhibition of 172 compounds that
belong to 11 different chemistry families. A model able to describe more than
68.5% of the variance in the experimental activity was developed with the use of
the mentioned approach. In contrast, none of the five different approaches,
including the use of Randic Molecular Profiles, Geometrical, RDF, 3D-MORSE and
WHIM descriptors was able to explain more than 62.4% of the variance in the
mentioned property with the same number of variables in the equation. Finally,
after extracting five compounds considered by us as outliers the model was able
to describe more than 72.5% of the variance in the experimental activity.
PMID- 17030482
TI - Structure-based pharmacophore of COX-2 selective inhibitors and identification of
original lead compounds from 3D database searching method.
AB - A four-point pharmacophore of COX-2 selective inhibitors was derived from a
training set of 16 compounds, using the Catalyst program. It consists of a H bond
acceptor, two hydrophobic groups and an aromatic ring, in accordance with SAR
data of the compounds and with topology of the COX-2 active site. This
hypothesis, combined with exclusion volume spheres representing important
residues of the COX-2 binding site, was used to virtually screen the Maybridge
database. Eight compounds were selected for an in vitro enzymatic assay. Five of
them show COX-2 inhibition close to that of nimesulide and rofecoxib, two
reference COX-2 selective inhibitors. As a result, structure-based pharmacophore
generation was able to identify original lead compounds, inhibiting the COX-2
isoform.
PMID- 17030483
TI - Structural modifications of benzanilide derivatives, effective potassium channel
openers. X.
AB - Large-conductance calcium-activated potassium (BK) channels are involved in many
fundamental cell functions. Consistently, the ability to activate BK channels by
exogenous compounds is considered as a promising pharmacodynamic pattern for the
potential treatment of several pathologies. In this perspective, the development
of new and selective BK-openers can be considered as an actual field of research.
This paper reports the synthesis and pharmacological evaluation of new
benzanilides, useful for deepening the comprehension of the structure-activity
relationships, emerged in previous studies on this class of BK-activators. From a
structural point of view, these benzanilides belong to a general class of BK
activators, showing a common pharmacophoric model, consisting of two aryl groups
linked through an appropriate "spacer" and the almost obligatory presence of a
phenolic hydroxyl. In particular, a new series of benzanilides, in which the
phenyl rings have been widely changed both on the acidic portion and the basic
one of the amide spacer, were synthesised. Their vasorelaxing effects, induced
through the activation of BK channels, were also evaluated. Although many
compounds exhibited effects which could not be attributed to the activation of BK
channels, two derivatives showed a clear profile of BK-activators with
vasodilator activity comparable to or slightly lower than that recorded for the
reference benzimidazolone NS1619. A further molecular modelling approach allowed
us to obtain a molecular electrostatic potential feature which suggests a
suitable interaction with the receptor site of the BK channel, from a tri
dimensional point of view. This approach seems to represent a further
contribution for the development of new BK-activators, designed on the basis of
the pharmacophoric model above-mentioned.
PMID- 17030484
TI - Synthesis and biological evaluation of new 4H-pyrano[2,3-b]quinoline derivatives
that block acetylcholinesterase and cell calcium signals, and cause
neuroprotection against calcium overload and free radicals.
AB - The synthesis and biological evaluation of ethyl 5-amino-4-(3-pyridyl)-2-methyl
6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinoline-3-carboxylates (9-11) is described.
We have found that these compounds inhibit AChE with a mild potency, mitigates
the [Ca(2+)](c) triggered by high K(+), and cause neuroprotection against Ca(2+)
overloading and free radical-induced neuronal death.
PMID- 17030485
TI - [Medical care for HIV infection in France in 2005, the NADIS cohort study on 7416
patients].
AB - OBJECTIVE: This study had for aim to evaluate the immuno-virological and
therapeutic profile of a cohort of 7416 HIV-1 infected patients followed in six
French hospital with the Nadis software. METHOD: This cross sectional and
retrospective study was performed between June 1, 2004 and June 1, 2005. We
analyzed the demographic (sex, age, HIV infection route), immunovirological, and
therapeutic characteristics (last treatment prescribed) of the 7416 cohort
patients. RESULTS: The mean age was 43 years, 29% were women and 29% HCV/HBV co
infected. The viral load was 1.9 log(10)copies/ml (IQR: 1.5-3.3) and the CD4
cells count was 452/mm(3) [IQR: 306-630]. Among the 5,913 antiretroviral treated
patients, VL was less than 200 copies/ml for 74.7% of patients and 50% of them
had a CD4 cell count superior to 500/mm(3); the drug regimen was 2 or 3
nucleosides reverse transcriptase inhibitors (NRTI) combined with one protease
inhibitor (88% Ritonavir boosted) in 42% of the patients, 26% of them were
treated with 2 NRTI and 1 non-NRTI, and 14% with 3NRTI. Patients with
undetectable VL were followed 5.1/year versus 7.2 for non- VL controlled patients
(P<10(-3)). The heterosexual route predominated among the new 531 HIV-diagnosed
patients among whom 25% had a median CD4 cell count of 242/ m(3). CONCLUSION:
Close to 75% of antiretroviral treated patients had a VL<200 copies/ml but 15%
kept a low CD4 cell count. The characteristics of recently diagnosed HIV positive
patients stresses the need for more information on prevention and an early
diagnosis.
PMID- 17030486
TI - Clinical and biological abnormalities in patients after fasciolosis treatment.
AB - OBJECTIVE: The aim of this communication was to report clinical disorders and
biological abnormalities in patients followed over a 3- to 18-year period after
the last date of fasciolosis treatment. These observations were noted in 87
individuals (out of 711) during a 30-year epidemiological survey. RESULTS: We
noted diffuse pain in the right hypochondrium, persisting 2 to 6 years after
treatment (3.7% of persons), and weight loss appearing during treatment and
persisting afterwards (2.1%). CONCLUSIONS: Our current state of knowledge leads
us to asking whether pain in the right hypochondrium and weight loss would not be
due to the presence of persistent hepatic lesions following fasciolosis
treatment. Other investigations in patients after treated fasciolosis are
necessary to confirm these abnormalities and determine their frequency.
PMID- 17030487
TI - [Is liver biopsy still useful?].
PMID- 17030488
TI - [Pulmonary thrombosis as a complication of Mediterranean spotted fever].
AB - INTRODUCTION: Thromboembolic complications were uncommon in mediterranean spotted
fever. OBSERVATION: We report a case of 55-years- old man who was admitted for
mediterranean spotted fever. Two days later, the patient developed chest pain due
to a pulmonary thrombosis confirmed by angio-CT. The outcome was good with
heparin therapy. The investigation for another cause of thrombosis was negative.
CONCLUSION: Mediterranean spotted fever is usually a moderately severe self
limited illness. Pulmonary thrombosis was uncommon associated with severe
disease.
PMID- 17030491
TI - Experiences of service user and carer participation in health care education.
AB - The agenda of involving service users and their carers more meaningfully in the
development, delivery and evaluation of professional education in health is
gaining in importance. The paper reports on a symposium which presented three
diverse initiatives, established within a school of nursing and midwifery in the
United Kingdom. These represent different approaches and attempts to engage
service users and in some instances carers more fully in professional education
aimed at developing mental health practitioners. Each is presented as achieving
movement on a continuum of participation from service users as passive recipients
to service users as collaborators and co-researchers. The paper concludes with a
discussion of the lessons to be learnt which will hopefully stimulate service
user involvement on a wider basis.
PMID- 17030490
TI - [Is subclinical hypothyroidism a cardiovascular risk factor?].
AB - OBJECTIVES: Subclinical hypothyroidism defined by the presence of elevated TSH
levels but normal free T4 level is a common situation. Its consequences on health
are yet on debate and the interest of a precocious treatment remains surrounded
by controversy. KEY POINTS: The relationship between subclinical hypothyroidism
and cardiovascular disease has been evaluated by several cross-sectional and
longitudinal studies. Subclinical hypothyroidism has direct but subtle effects on
the heart function, on the peripheral vascular resistance, and is associated with
a mild elevation of LDL-cholesterol levels; all abnormalities may be partly
reversed by a thyroxine supplementation. Data of the literature give insufficient
evidence as to whether subclinical hypothyroidism is an independent
cardiovascular risk factor. However treatment of subjects with TSH levels up or
near to 10 mU/l would probably be beneficial in the prevention of cardiovascular
disease. FUTURE PROSPECTS: Based on observational and interventional studies
there are some arguments on the benefit of euthyroidism restoration only in
patients with TSH levels superior to 10 mU/l.
PMID- 17030492
TI - Attitudes towards disability in an undergraduate nursing curriculum: a literature
review.
AB - In the process of introducing a new disability unit into an undergraduate nursing
curriculum in a New Zealand educational setting, the opportunity arose to conduct
a small study comparing the attitudes of student nurses towards people with
disabilities. This paper discusses the literature reviewed, which formed the
basis for the study. A range of perspectives and research was identified that
explored societal and nurses' attitudes, disability studies in undergraduate
nursing curricula, the impact of nurses' attitudes on patient care, and
interventions for changing those attitudes. Effective nursing care can be
severely compromised through negative attitudes, and concerns are expressed at
the lack of attention given to this issue in nursing curricula generally. The
literature showed that combining educational approaches with opportunities for
student nurses to interact with disabled people provides the most effective means
for student nurses to develop positive attitudes towards disabled people. The
goal for nurse educators is to ensure the inclusion of disability studies as a
core component in undergraduate nursing education.
PMID- 17030493
TI - Indirect effects of childhood pneumococcal vaccination on pneumococcal carriage
among adults and older children in Australian Aboriginal communities.
AB - Nasopharyngeal carriage of Streptococcus pneumoniae in unimmunised adults and
older children in three remote Australian Aboriginal communities was compared in
2002 and 2004. Universal childhood pneumococcal vaccination with a catch-up
program was introduced in late 2001. Carriage prevalence across all age groups of
pneumococcal serotypes included in the 7-valent vaccine was 10% in both 2002 and
2004 (12 and 30 months after introduction of vaccination). This carriage
prevalence was lower than anticipated. It is likely that indirect effects of
childhood vaccination occurred before the 2002 survey. To further assess indirect
effects on carriage of childhood pneumococcal vaccination, data prior to 2002 are
required. Between 12 and 30 months following introduction of conjugate
pneumococcal vaccination, indirect effects on carriage were unchanged.
PMID- 17030494
TI - Modelling the co-occurrence of Streptococcus pneumoniae with other bacterial and
viral pathogens in the upper respiratory tract.
AB - Otitis media (OM) is a major burden for all children, particularly for Australian
Aboriginal children. Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus
influenzae and viruses (including rhinovirus and adenovirus) are associated with
OM. We investigated nasopharyngeal microbial interactions in 435 samples
collected from 79 Aboriginal and 570 samples from 88 non-Aboriginal children in
Western Australia. We describe a multivariate random effects model appropriate
for analysis of longitudinal data, which enables the identification of two
independent levels of correlation between pairs of pathogens. At the microbe
level, rhinovirus infection was positively correlated with carriage of S.
pneumoniae, H. influenzae and M. catarrhalis, and adenovirus with M. catarrhalis.
Generally, there were positive associations between bacterial pathogens at both
the host and microbe level. Positive viral-bacterial associations at the microbe
level support previous findings indicating that viral infection can predispose an
individual to bacterial carriage. Viral vaccines may assist in reducing the
burden of bacterial disease.
PMID- 17030495
TI - Population dynamics of Bordetella pertussis in Finland and Sweden, neighbouring
countries with different vaccination histories.
AB - Pertussis is an infectious disease of the respiratory tract in humans caused by
Bordetella pertussis. Despite extensive vaccinations, pertussis has remained
endemic and re-emerged. In Finland, a whole-cell pertussis vaccine has been used
since 1952 with high coverage. In Sweden, whole-cell vaccinations were introduced
in 1953 but ceased in 1979, and pertussis vaccinations with acellular vaccines
were introduced in 1996. Two epidemic peaks occurred in Sweden in 1999 and 2002
and in Finland in 1999 and 2003. We compared Finnish (N=193) and Swedish (N=455)
B. pertussis isolates circulating in 1998-2003 together with vaccine strains used
in these neighbouring countries with different vaccination histories. The
isolates were analysed by serotyping, genotyping of pertussis toxin S1 subunit
and pertactin, and pulsed-field gel electrophoresis. The results suggest that the
sequential epidemics were caused by clonal expansion of a certain B. pertussis
strain possibly transmitted from Sweden to Finland. The roles of antigenic
variation in immunity-driven evolution of B. pertussis in both countries are
discussed.
PMID- 17030496
TI - Contrasting roles for reactive oxygen species and nitric oxide in the innate
response to pulmonary infection with Streptococcus pneumoniae.
AB - The pulmonary innate response to low-dose bacterial challenge requires
functioning alveolar macrophages (AM) but also subsequent macrophage apoptosis.
To address the role of reactive oxygen species (ROS) and nitric oxide (NO) in AM
apoptosis, sub-clinical Streptococcus pneumoniae infection was established in
gp91(phox-/-) and inducible NO synthase deficient (iNOS(-/-)) mice. Both AM
apoptosis and the number of macrophages containing apoptotic bodies are reduced
in iNOS(-/-) as compared to control or gp91(phox-/-) mice. iNOS(-/-) mice recruit
neutrophils and generate TNF-alpha to compensate for impaired AM competence but
ROS deficiency has no apparent effect on AM function in this model.
PMID- 17030497
TI - An overview of acute otitis media in Australian Aboriginal children living in
remote communities.
AB - Australian Aboriginal children experience early, persistent and severe middle ear
infections. We conducted a review of the medical literature that addressed acute
otitis media (AOM) in Australian Aboriginal children. Comparisons were made with
the recent guidelines on the diagnosis and management of AOM prepared by the
American Academies of Pediatrics and Family Physicians (AAP & AAFP 2004). Otitis
media in Aboriginal children living in remote communities begins in the first 3
months of life following early bacterial colonisation. Young children with
persistent signs of suppurative disease (bulging of the tympanic membrane or
middle ear discharge) are probably most at risk of developing chronic suppurative
otitis media.
PMID- 17030498
TI - Reassortment between human A(H3N2) viruses is an important evolutionary
mechanism.
AB - Phylogenetic relationships of whole genomes of H3N2 viruses circulating in
Germany during a 6-year period from 1998 to 2005 revealed the co-circulation of
different lineages of viruses. Multiple reassortment events occurred during this
time between viruses belonging to different lineages or different subgroups.
Strains isolated during 1998-1999 were characterised by a surprisingly high
heterogeneity and multiple reassortment events. Seventy percent of the examined
1998-1999 viruses had completely different genome compositions. To our knowledge,
such an exceptional high proportion of different reassortant strains,
encompassing all eight genome segments, have not been described before. In
contrast, only one reassortant virus was prevalent during 1999-2000 even though
two of the three 1998-1999 lineages were co-circulating. Reassortant viruses were
isolated also in each of the other seasons. However, the proportion of H3N2
viruses with different genome compositions varied from season to season. Strains
with a reassortant NA played an important role and were also detected during 2003
2004 and 2004-2005 accounting for 45% and 70% of the circulating H3N2 viruses,
respectively. Moreover, different reassortment events occurring during these
seasons included also the PB1, PB2 and NP genes. The results presented here
emphasize that genetic reassortment is an important factor in the evolution of
H3N2 viruses and highlight the need for a comprehensive analysis of influenza
viruses, especially with regard to the annual vaccine composition.
PMID- 17030499
TI - A comparison of the Alcohol Use Disorder Identification Test (AUDIT) in general
population surveys in nine European countries.
AB - AIMS: This study explored the suitability of the Alcohol Use Disorder
Identification Test (AUDIT) for cross-national comparable estimates of problem
drinking in general populations. On the item level the focus is on responsiveness
to cross-national and gender differences. For the set of items the focus is on
intercorrelations between items, indicating to what extent the AUDIT constitutes
a scale. METHODS: General population surveys from nine European countries were
included. Cross-tabulations were used to analyse cross-national and gender
differences in scores on the items. Reliability analysis was used to analyse
intercorrelations between the items. RESULTS: The items 'blackouts' (men and
women) and 'guilt and remorse' (women) are the most frequently reported
consequences. Gender differences tended to be smaller for 'guilt and remorse' and
'concern of others', and largest for 'morning drinking'. The reliability analysis
shows that in eight of the nine countries frequency of drinking lowers the alpha.
Injury and concern of others lead to a lower internal consistency in three
countries. CONCLUSIONS: There was sufficient variation between countries in the
pattern of responses and variation in gender differences to conclude that the set
of consequence items was responsive to national and gender differences in problem
drinking. Frequency of drinking was not a good indicator of problem drinking. The
country differences in item total correlations of consequences might be due to
differences in how these items are interpreted. Decisions on which items to
include in an instrument to allow comparison of estimates of problem drinking
cross-nationally require studies on how these items are interpreted in general
populations of different countries.
PMID- 17030500
TI - Social inequalities in alcohol consumption and alcohol-related problems in the
study countries of the EU concerted action 'Gender, Culture and Alcohol Problems:
a Multi-national Study'.
AB - AIMS: We investigated the presence of social inequalities of alcohol use and
misuse using educational attainment as an indicator of socio-economic status in
15 countries: Sweden, Norway, Finland, Germany, The Netherlands, Switzerland,
Hungary, the Czech Republic, Israel, Brazil, and Mexico. METHODS: Study surveys
were independently conducted and the data centrally analysed. Most samples were
national. Survey modes and sample sizes varied. The age range was restricted to
between 25 and 59 years of age. Socio-economic status was measured by educational
level. Multiple logistic regressions were employed to calculate age-adjusted odds
ratios for men and women in each country by educational level for current
drinking status, heavy drinking (>or=20 g ethanol per day for women, >or=30 g a
day for men), heavy episodic (binge) drinking, and alcohol-related problems
(using AUDIT). RESULTS: Men and women demonstrated similar patterns in
inequalities with regard to current drinking status within a country. In Germany,
The Netherlands, France, Switzerland, and Austria higher educated women were most
likely to drink heavily, while among men the lower educated were more at risk in
most countries. For heavy episodic drinking, almost no significant differences
were evident among women, but for men a social gradient was observable with lower
educated being more at risk in several countries. Among five countries with data
from the AUDIT, men of lower education in Finland, Czech Republic, and Hungary
had higher risks to report problems. Nordic countries shared a common pattern in
social inequalities as did two Latin American countries, while a mixed picture
was observed for middle European countries. Social inequalities in the two Latin
American countries display a pattern emerging in other research on developing
countries: namely that those in the higher educated groups are more likely to
consume alcohol in a risky manner. CONCLUSIONS: Patterns in the distribution of
social inequalities are not universal. Social inequalities in alcohol use differ
by gender according to alcohol measure used and differ also across groups of
countries. These variations should be taken into account when formulating
international and cross-cultural alcohol policies.
PMID- 17030501
TI - Introduction to special issue 'Gender, Culture and Alcohol Problems: a Multi
national Study'.
AB - This paper provides an introduction to a series of articles reporting results
from the EU concerted action "Gender, Culture and Alcohol Problems: A Multi
national Study" which examined differences in drinking among women and men in 13
European and two non-European countries. The gender gap in alcohol drinking is
one of the few universal gender differences in human social behavior. However,
the size of these differences varies greatly from one society to another. The
papers in this issue examine, across countries, (1) men's and women's drinking
patterns, (2) the prevalence of men's and women's experience of alcohol-related
problems, (3) gender differences in social inequalities in alcohol use and abuse,
(4) gender differences in the influence of combinations of social roles on heavy
alcohol use, and (5) how societal-level factors predict women's and men's alcohol
use and problems on a regional and global level. Country surveys were
independently conducted and then centralized at one institution for further data
standardization and processing. Several results indicated that the greater the
societal gender equality in a country, the smaller the gender differences in
drinking behavior. In most analyses the smallest gender differences in drinking
behaviour were found in Nordic countries, followed by western and central
European countries, with the largest gender differences in countries with
developing economies.
PMID- 17030502
TI - Gender and cultural differences in the association between family roles, social
stratification, and alcohol use: a European cross-cultural analysis.
AB - AIMS: First, this paper investigates (i) gender differences in associations of
social stratification, family roles, and heavy drinking, and (ii) country
differences in these associations. Second, it seeks to explain country
differences in the associations of social stratification and family roles with
alcohol consumption by societal level variables. METHODS: Survey data of 25 to 49
years-old from eight European countries were used. Logistic regressions were used
to analyse gender differences in the association between family roles (marriage,
having children), social stratification (education, employment), and heavy
drinking (>20 g/day for women; 30 g/day for men). Gender differences were tested
by means of interactions between gender and social stratification/family roles.
Structural measures of work desirability, social welfare, and gender equity were
used to explain differences in associations across countries. RESULTS: The
associations between social stratification, family roles, and heavy drinking
varied across gender and countries. A country's social welfare system was
associated with heavy drinking only among women. Women in countries with a strong
social welfare system, such as Nordic countries, tended to drink more heavily if
employed, having lower formal education, and a non-traditional family role. In
countries with weak social welfare systems or work desirability, heavy drinking
was associated with high education, while effects of family roles and employment
were small. CONCLUSIONS: It appeared that the social welfare system and gender
equity of a country determines to a large extent how education, employment, and
family roles are associated with heavy drinking.
PMID- 17030503
TI - The influence of societal level factors on men's and women's alcohol consumption
and alcohol problems.
AB - AIMS: To identify the pattern of gender differences in drinking across societies,
and to its association with other societal characteristics. METHODS: The
aggregated results of GENACIS project surveys in 29 countries were examined and
were compared with other characteristics of these societies. RESULTS: In all the
participating societies men's drinking was more prevalent and heavier than
women's drinking. Differences between countries in the gender gap in drinking
were strongly associated with women's position in society, as well as with
modernization. Similar results were obtained for indicators of alcohol's adverse
consequences. CONCLUSIONS: Gender differences should be studied not only as
individual behaviours, but also as societal traits, associated with other
characteristics of the social system.
PMID- 17030504
TI - Drinking patterns and their gender differences in Europe.
AB - AIMS: To compare drinking habits and to examine differences between drinking
cultures in different regions and countries in Europe; to examine gender
differences in drinking habits and to compare them over countries. METHODS: Data
consisted of independently conducted, centrally analysed surveys in the general
population aged 20-64 years in 14 European countries. Central measures were
abstention, frequency and volume of drinking overall and by beverage type,
amounts drunk per drinking day, and heavy episodic drinking. RESULTS: There were
clear gender differences in all drinking measures, except for wine drinking.
Differences between genders were often smaller than average in northern Europe.
Gender ratios did not show systematic changes by age, with the exception that
young men and women differed less than older men and women in the frequency of
heavy episodic drinking. The results on beverage preferences indicate that the
distinction among wine/beer/spirits cultures have implicitly been based on male
drinking. Our expectation was for more daily light drinking integrated in
everyday life in the Mediterranean countries, more heavy episodic drinking
associated with weekends and celebrations in the North, with the traditional beer
countries somewhere in between. The differences observed were usually in the
direction expected. However, no country represented an ideal type of drinking
culture, i.e. drinking for 'mood-changing effects' only or for 'nutritional
purposes' only; all countries were mixtures of these two extremes. CONCLUSIONS:
There were clear and consistent gender differences in all countries, while the
differences in drinking between countries and regions were not as obvious.
PMID- 17030505
TI - PbGCbeta is essential for Plasmodium ookinete motility to invade midgut cell and
for successful completion of parasite life cycle in mosquitoes.
AB - When malaria parasites enter to mosquitoes, they fertilize and differentiate to
zygotes and ookinetes. The motile ookinetes cross the midgut cells and arrive to
the basement membranes where they differentiate into oocysts. The midgut
epithelium is thus a barrier for ookinetes to complete their life cycle in the
mosquitoes. The ookinetes develop gliding motility to invade midgut cells
successfully, but the molecular mechanisms behind are poorly understood. Here, we
identified a single molecule with guanylate cyclase domain and N-terminal P-type
ATPase like domain in the rodent malaria parasite Plasmodium berghei and named it
PbGCbeta. We demonstrated that transgenic parasites in which the PbGCbeta gene
was disrupted formed normal ookinetes but failed to produce oocyst. Confocal
microscopic analysis showed that the disruptant ookinetes remained on the surface
of the microvilli. The disruptant ookinetes showed severe defect in motility,
resulting in failure of parasite invasion of the midgut epithelium. When the
disruptant ookinetes were cultured in vitro, they transformed into oocysts and
sporozoites. These results demonstrate that PbGCbeta is essential for ookinete
motility when passing through the midgut cells, but not for further development
of the parasites.
PMID- 17030506
TI - Involvement of p38 MAP kinase in not only activation of the phagocyte NADPH
oxidase induced by formyl-methionyl-leucyl-phenylalanine but also determination
of the extent of the activity.
AB - Activated NADPH oxidase in neutrophils produces superoxide. We investigated the
role of p38 MAP kinase in activating NADPH oxidase stimulated by the bacteria
derived peptide fMLP. fMLP-stimulated superoxide production was completely
abolished by SB203580, a p38 MAP kinase inhibitor, whereas anisomycin, a p38 MAP
kinase activator, did not induce superoxide production, indicating that p38 MAP
kinase was essential, but not sufficient, for NADPH oxidase activation.
Anisomycin pretreatment strongly activated p38 MAP kinase in fMLP-stimulated
cells, accompanied by greatly increased superoxide production, suggesting that
p38 MAP kinase determines the extent of the fMLP-stimulated NADPH oxidase
activity. Furthermore, superoxide production was remarkably reactivated by
cytochalasin B addition after fMLP-stimulated production had disappeared, and
this was correlated with highly activated p38 MAP kinase. These results suggest
that p38 MAP kinase is involved not only in activating NADPH oxidase stimulated
by fMLP but also in determining the extent of its activity.
PMID- 17030507
TI - Selective proteolysis of apolipoprotein B-100 by Arg-gingipain mediates
atherosclerosis progression accelerated by bacterial exposure.
AB - Epidemiological studies suggest the association of periodontal infections with
atherosclerosis, however, the mechanism underlying this association remains
poorly understood. Porphyromonas gingivalis is the primary etiologic agent of
adult periodontitis and produces a unique class of cysteine proteinases
consisting of Arg-gingipain (Rgp) and Lys-gingipain (Kgp). To elucidate key
mechanisms for progression of atherosclerosis by P. gingivalis infection, we
tested the effects of the disruption of genes encoding Rgp and/or Kgp and
inhibitors specific for the respective enzymes on atherosclerosis progression in
apolipoprotein E-knockout mice. Repeated intravenous injection of wild-type P.
gingivalis resulted in an increase in atherosclerotic lesions as well as an
increase in the serum LDL cholesterol and a decrease of HDL cholesterol in these
animals. LDL particles in P. gingivalis-injected animals were modified as a
result of selective proteolysis of apoB-100 in LDL particles. This modification
of LDL by P. gingivalis resulted in an increase in LDL uptake by macrophages and
consequent foam cell formation in vitro. The atherosclerotic changes induced by
P. gingivalis infection were attenuated by disruption of Rgp-encoding genes or by
an Rgp-specific inhibitor. Our results indicate that degradation of apoB-100 by
Rgp plays a crucial role in the promotion of atherosclerosis by P. gingivalis
infection.
PMID- 17030508
TI - An RNA aptamer that discriminates bovine factor IX from human factor IX.
AB - An RNA aptamer has been selected by SELEX against bovine factor IX using an RNA
pool containing 74-nucleotides randomized region. Selected RNA aptamer (Clone 5)
could discriminate bovine factor IX effectively from human factor IX.
Interestingly, the nucleotide regions 73-78 and 80-83 of the selected aptamer
were determined to be important for bovine factor IX-binding using phosphate
interference. Based on phosphate interference and binding studies the minimal
motif for aptamer with discriminating ability is found with the nucleotide
regions from 65 to 106. The discriminating ability of this mini aptamer is
calculated as more than 1,000 fold. The equilibrium dissociation constant (K(d))
for the above complex was 10 nM as determined by surface plasmon resonance. Based
on the available structural informations, probable binding site of aptamer on the
target was predicted.
PMID- 17030509
TI - Phosphatidylinositol 3-kinase-dependent modulation of carnitine
palmitoyltransferase 1A expression regulates lipid metabolism during
hematopoietic cell growth.
AB - An abundant supply of extracellular nutrients is believed to be sufficient to
suppress catabolism of cellular macromolecules. Here we show that, despite
abundant extracellular nutrients, interleukin-3-deprived hematopoietic cells
begin to catabolize intracellular lipids. Constitutive Akt activation blunts the
increased beta-oxidation that accompanies growth factor withdrawal, and in growth
factor-replete cells, phosphatidylinositol 3-kinase (PI3K) signaling is required
to suppress lipid catabolism. Surprisingly, PI3K and Akt exert these effects by
suppressing expression of the beta-oxidation enzyme carnitine
palmitoyltransferase 1A (CPT1A). Cells expressing a short hairpin RNA against
CPT1A fail to induce beta-oxidation in response to growth factor withdrawal and
are unable to survive glucose deprivation. When CPT1A is constitutively
expressed, growth factor stimulation fails to repress beta-oxidation. As a
result, both net lipid synthesis and cell proliferation are diminished. Together,
these results demonstrate that modulation of CPT1A expression by PI3K-dependent
signaling is the major mechanism by which cells suppress beta-oxidation during
anabolic growth.
PMID- 17030510
TI - Protein kinase C-induced activation of a ceramide/protein phosphatase 1 pathway
leading to dephosphorylation of p38 MAPK.
AB - Recently we showed that, in human breast cancer cells, activation of protein
kinase C by 4beta-phorbol 12-myristate 13-acetate (PMA) produced ceramide formed
from the salvage pathway (Becker, K. P., Kitatani, K., Idkowiak-Baldys, J.,
Bielawski, J., and Hannun, Y. A. (2005) J. Biol. Chem. 280, 2606-2612). In this
study, we investigated intracellular signaling events mediated by this novel
activated pathway of ceramide generation. PMA treatment resulted in transient
activation of mitogen-activated protein kinases (ERK1/2, JNK1/2, and p38)
followed by dephosphorylation/inactivation. Interestingly, fumonisin B1 (FB1), an
inhibitor of the salvage pathway, attenuated loss of phosphorylation of p38,
suggesting a role for ceramide in p38 dephosphorylation. This was confirmed by
knock-down of longevity-assurance homologue 5, which partially suppressed the
formation of C(16)-ceramide induced by PMA and increased the phosphorylation of
p38. These results demonstrate a role for the salvage pathway in feedback
inhibition of p38. To determine which protein phosphatases act in this pathway,
specific knock-down of serine/threonine protein phosphatases was performed, and
it was observed that knock-down of protein phosphatase 1 (PP1) catalytic subunits
significantly increased p38 phosphorylation, suggesting activation of PP1 results
in an inhibitory effect on p38. Moreover, PMA recruited PP1 catalytic subunits to
mitochondria, and this was significantly suppressed by FB1. In addition, phospho
p38 resided in PMA-stimulated mitochondria. Upon PMA treatment, a mitochondria
enriched/purified fraction exhibited significant increases in C(16)-ceramide, a
major ceramide specie, which was suppressed by FB1. Taken together, these data
suggest that accumulation of C(16)-ceramide in mitochondria formed from the
protein kinase C-dependent salvage pathway results at least in part from the
action of longevity-assurance homologue 5, and the generated ceramide modulates
the p38 cascade via PP1.
PMID- 17030511
TI - Swt1, a novel yeast protein, functions in transcription.
AB - The conserved TREX complex couples transcription to nuclear mRNA export. Here, we
report that the uncharacterized open reading frame YOR166c genetically interacts
with TREX complex components and encodes a novel protein named Swt1 for
"synthetically lethal with TREX." Co-immunoprecipitation experiments show that
Swt1 also interacts with the TREX complex biochemically. Consistent with a
potential role in transcription as suggested by its interaction with TREX, Swt1
localizes mainly to the nucleus. Importantly, deletion of Swt1 leads to decreased
transcription. Taken together, these data suggest that Swt1 functions in gene
expression in conjunction with the TREX complex.
PMID- 17030512
TI - Dynamics of myosin heavy chain gene regulation in slow skeletal muscle: role of
natural antisense RNA.
AB - The evolutionarily conserved order of the skeletal muscle myosin heavy chain
(MHC) genes and their close tandem proximity on the same chromosome are
intriguing and may be important for their coordinated regulation. We investigated
type II MHC gene regulation in slow-type muscle fibers undergoing a slow to fast
MHC transformation in response to inactivity, 7 days after spinal cord isolation
(SI) in rats. We examined the transcriptional products of both the sense and
antisense strands across the IIa-IIx-IIb MHC gene locus. A strand-specific
reverse transcription (RT)-PCR approach was utilized to study the expression of
the mRNA, the primary transcript (pre-mRNA), the antisense RNA overlapping the
MHC genes, and both the intergenic sense and antisense RNAs. Results showed that
the mRNA and pre-mRNA of each MHC had a similar response to SI, suggesting
regulation of these genes at the transcriptional level. In addition, we detected
previously unknown antisense strand transcription that produced natural antisense
transcripts (NATs). RT-PCR mapping of the RNA products revealed that the
antisense activity resulted in the formation of three major products: aII, xII,
and bII NATs (antisense products of the IIa, IIx, and IIb genes, respectively).
The aII NAT begins in the IIa-IIx intergenic region in close proximity to the IIx
promoter, extends across the 27-kb IIa MHC gene, and continues to the IIa MHC
gene promoter. The expression of the aII NAT was significantly up-regulated in
muscles after SI, was negatively correlated with IIa MHC gene expression, and was
positively correlated with IIx MHC gene expression. The exact role of the aII NAT
is not clear; however, it is consistent with the inhibition of IIa MHC gene
transcription. In conclusion, NATs may mediate cross-talk between adjacent genes,
which may be essential to the coordinated regulation of the skeletal muscle MHC
genes during dynamic phenotype shifts.
PMID- 17030513
TI - S100A16, a novel calcium-binding protein of the EF-hand superfamily.
AB - S100A16 protein is a new and unique member of the EF-hand Ca(2+)-binding
proteins. S100 proteins are cell- and tissue-specific and are involved in many
intra- and extracellular processes through interacting with specific target
proteins. In the central nervous system S100 proteins are implicated in cell
proliferation, differentiation, migration, and apoptosis as well as in cognition.
S100 proteins became of major interest because of their close association with
brain pathologies, for example depression or Alzheimer's disease. Here we report
for the first time the purification and biochemical characterization of human and
mouse recombinant S100A16 proteins. Flow dialysis revealed that both homodimeric
S100A16 proteins bind two Ca(2+) ions with the C-terminal EF-hand of each
subunit, the human protein exhibiting a 2-fold higher affinity. Trp fluorescence
variations indicate conformational changes in the orthologous proteins upon
Ca(2+) binding, whereas formation of a hydrophobic patch, implicated in target
protein recognition, only occurs in the human S100A16 protein. In situ
hybridization analysis and immunohistochemistry revealed a widespread
distribution in the mouse brain. Furthermore, S100A16 expression was found to be
astrocyte-specific. Finally, we investigated S100A16 intracellular localization
in human glioblastoma cells. The protein was found to accumulate within nucleoli
and to translocate to the cytoplasm in response to Ca(2+) stimulation.
PMID- 17030514
TI - CKAP4/p63 is a receptor for the frizzled-8 protein-related antiproliferative
factor from interstitial cystitis patients.
AB - Antiproliferative factor (APF) is a low molecular weight sialoglycopeptide that
is secreted by bladder cells from interstitial cystitis patients and is a potent
inhibitor of both normal bladder epithelial and bladder carcinoma cell
proliferation. We hypothesized that APF may produce its antiproliferative effects
by binding to a transmembrane receptor. This study demonstrates that cytoskeleton
associated protein 4/p63 (CKAP4/p63), a type II transmembrane receptor, binds
with high affinity to APF. The antiproliferative activity of APF is effectively
inhibited by preincubation with anti-CKAP4/p63-specific antibodies, as well as by
short interfering RNA knockdown of CKAP4/p63. Immunofluorescent confocal
microscopy showed co-localization of anti-CKAP4/p63 and rhodamine-labeled
synthetic APF binding in both cell membrane and perinuclear areas. APF also
inhibits the proliferation of HeLa cervical carcinoma cells that are known to
express CKAP4/p63. These data indicate that CKAP4/p63 is an important epithelial
cell receptor for APF.
PMID- 17030515
TI - Efficacy of daptomycin in the treatment of experimental endocarditis due to
susceptible and multidrug-resistant enterococci.
AB - OBJECTIVES: Daptomycin was tested in vitro and in rats with experimental
endocarditis against the ampicillin-susceptible and vancomycin-susceptible
Enterococcus faecalis JH2-2, the vancomycin-resistant (VanA type) mutant of
strain JH2-2 (strain JH2-2/pIP819), and the ampicillin-resistant and vancomycin
resistant (VanB type) Enterococcus faecium D366. METHODS: Rats with catheter
induced aortic vegetations were treated with doses simulating intravenously
kinetics in humans of daptomycin (6 mg/kg every 24 h), amoxicillin (2 g every 6
h), vancomycin (1 g every 12 h) or teicoplanin (12 mg/kg every 12 h). Treatment
was started 16 h post-inoculation and continued for 2 days. RESULTS: MICs of
daptomycin were 1, 1 and 2 mg/L, respectively, for strains JH2-2, JH2-2/pIP819
and D366. In time-kill studies, daptomycin showed rapid (within 2 h) bactericidal
activity against all strains. Daptomycin was highly bound to rat serum proteins
(89%). In the presence of 50% rat serum, simulating free concentrations,
daptomycin killing was maintained but delayed (6-24 h). In vivo, daptomycin
treatment resulted in 10 of 12 (83%), 9 of 11 (82%) and 11 of 12 (91%) culture
negative vegetations in rats infected with strains JH2-2, JH2-2/pIP819 and D366,
respectively (P < 0.001 compared to controls). Daptomycin efficacy was comparable
to that of amoxicillin and vancomycin for susceptible isolates. Daptomycin,
however, was significantly (P < 0.05) more effective than teicoplanin against the
glycopeptide-susceptible strain JH2-2 and superior to all comparators against
resistant isolates. CONCLUSIONS: These results support the use of the newly
proposed daptomycin dose of 6 mg/kg every 24 h for treatment of enterococcal
infections in humans.
PMID- 17030516
TI - Expression of the las and rhl quorum-sensing systems in clinical isolates of
Pseudomonas aeruginosa does not correlate with efflux pump expression or
antimicrobial resistance.
AB - OBJECTIVES: Quorum-sensing systems regulate expression of several virulence
factors and may affect the MexAB-OprM efflux system in Pseudomonas aeruginosa.
This study investigated the relationship between two quorum-sensing systems,
efflux pump MexAB-OprM expression and antimicrobial resistance in 33 clinical
isolates of P. aeruginosa. METHODS: Expression of the quorum-sensing regulatory
genes lasR and rhlR was assessed by real time RT-PCR. The autoinducer synthetase
genes lasI and rhlI and the regulatory genes mexT and mexS were characterized by
DNA sequencing. Production of pyocyanin and elastase in each of the isolates was
also determined. RESULTS: While there was a significant correlation between
expression of the quorum-sensing regulatory genes and production of pyocyanin and
elastase, there was no correlation with expression of mexA or with antimicrobial
resistance. There were no mutations in lasI, rhlI, mexT or mexS that correlated
with quorum-sensing expression. CONCLUSIONS: Increased activity of two quorum
sensing systems in P. aeruginosa does not contribute to increased mexA expression
or antimicrobial resistance.
PMID- 17030517
TI - spa typing of methicillin-resistant Staphylococcus aureus isolated from domestic
animals and veterinary staff in the UK and Ireland.
AB - OBJECTIVES: Region X of the protein A gene (spa) was sequenced from methicillin
resistant Staphylococcus aureus (MRSA) isolates originating from animals, humans
and the environment at veterinary hospitals in the UK and Ireland. MRSA
transmission between animals and veterinary staff was assessed on the basis of
spa typing, PFGE and epidemiological data. METHODS: MRSA isolates from dogs (n =
27), horses (n = 9), cats (n = 6), staff (n = 22) and environmental surfaces (n =
3) were analysed by PFGE and spa typing. Known contacts between human and animal
MRSA carriers were ascertained from the veterinary hospitals. RESULTS: All
feline, most canine (96%) and human (82%) isolates showed PFGE profiles that were
either indistinguishable (subtype A1) or closely related (subtypes A2-A10) to
that of the epidemic clone EMRSA-15 (CC22), whereas most equine isolates (88%)
were related to CC8 (types C, D, E and G). spa polymorphism enabled
discrimination among MRSA strains assigned to the same PFGE type. Fifteen spa
types clustering into two distinct groups were detected, with t032 being the most
prevalent (48%). The spa and PFGE types of MRSA isolated from seven staff members
were the same as those of strains isolated from infected animals attended by the
staff. CONCLUSIONS: Irrespective of geographical origin, MRSA isolated from
equine and small animal hospitals generally clustered into two distinct clonal
complexes, CC8 and CC22, respectively. The combined use of spa and PFGE typing
allowed better discrimination than each method used individually, and provided
useful information on MRSA transmission between animal and human individuals.
PMID- 17030518
TI - Impact of the Hospital Pharmacy Initiative for promoting prudent use of
antibiotics in hospitals in England.
AB - OBJECTIVES: In July 2003, the UK Department of Health announced an allocation of
12 million pounds sterling to hospital pharmacists to improve the monitoring and
control of anti-infective use over the ensuing 3 year period (the Hospital
Pharmacy Initiative, or HPI). Chief Pharmacists were asked to use this money for
developments to promote prudent antibiotic use and monitoring of antimicrobials
within their Trusts. This study aimed to evaluate the impact of the HPI funding,
which at the time had been in place for nearly 2 years, on pharmacy activities in
this area. METHODS: A postal questionnaire was sent to the pharmacy department of
each acute hospital Trust in England, aiming to provide a descriptive overview of
the activities of hospital pharmacy staff in the field of anti-infectives and to
explore the extent to which these activities were made possible by the HPI
funding. RESULTS: One hundred and forty-one specialist antimicrobial pharmacy
staff were employed in 130 responding Trusts; 89% were pharmacists, 7% pharmacy
technicians and the remainder administrative staff. Three-quarters of these staff
had been employed due to the funding, resulting in review of antimicrobial
prescribing guidelines, antibiotic audit projects and multidisciplinary work with
Microbiology/Infectious Diseases staff. Thirteen Trusts gave details of drug
acquisition cost savings; over the course of a year, these Trusts saved 1.1
million pounds sterling in total. CONCLUSIONS: The HPI funding has facilitated
greater interaction between Pharmacy and Microbiology/Infectious Diseases
departments than was previously possible. Significant reductions in antibiotic
acquisition costs have been demonstrated, though further work is warranted to
fully establish the impact of pharmacy activities on clinical and microbiological
outcomes.
PMID- 17030519
TI - Tigecycline does not induce proliferation or cytotoxin production by epidemic
Clostridium difficile strains in a human gut model.
AB - OBJECTIVES: Data on the risk of Clostridium difficile infection (CDI) associated
with specific antibiotics are difficult to obtain because of confounding clinical
factors. It is particularly important to evaluate the propensity of new
antibiotics to induce CDI. We have examined the propensity of tigecycline to
induce CDI using a human gut model. METHODS: We used a three-stage chemostat
human gut model to study the effects of tigecycline on indigenous gut microflora
and C. difficile. Two epidemic C. difficile were studied in separate experiments:
PCR ribotype 001 (UK, CD001) and PCR ribotype 027 (North America, CD027).
Tigecycline MICs for 39 C. difficile representing 19 distinct PCR ribotypes were
also determined. RESULTS: Tigecycline MICs were 0.06 mg/L for all the C.
difficile strains. Peak tigecycline concentrations in the gut model were 10.9 and
11.7 mg/L in CD027 and CD001 experiments, respectively. Tigecycline instillation
invoked marked decreases in numbers of bacteroides and bifidobacteria (10(7)
10(8) cfu/mL) and lesser reductions in facultative anaerobes. Despite markedly
altered gut microflora, CD001 and CD027 remained as spores for the duration of
the experiment, with no evidence of proliferation or cytotoxin production.
CONCLUSIONS: Tigecycline exposure did not induce C. difficile proliferation or
cytotoxin production despite reduced competing microflora. The potency of
tigecycline against C. difficile may contribute to the low risk of CDI induction.
Factors other than gut microflora colonization resistance may be important in
preventing C. difficile spore germination, proliferation and cytotoxin
production.
PMID- 17030520
TI - Coronary flow reserve in dilated cardiomyopathy: an important pathophysiological
tool to be considered among, but not instead of, other well-established
prognostic factors.
PMID- 17030521
TI - Results of the first clinical study of adjunctive CAldaret (MCC-135) in patients
undergoing primary percutaneous coronary intervention for ST-Elevation Myocardial
Infarction: the randomized multicentre CASTEMI study.
AB - AIMS: To examine the safety and efficacy of intravenous caldaret in patients with
large acute ST-elevation myocardial infarction (STEMI) undergoing percutaneous
coronary intervention (PCI). METHODS AND RESULTS: STEMI patients (n=387) with >
or =10 mm summed ST-deviation on electrocardiogram were randomized to receive a
48 h infusion of caldaret 57.5 mg [lower dose (LD)], caldaret 172.5 mg [higher
dose (HD)], or placebo, starting before PCI. Both HD and LD were well tolerated.
In 247 patients with pre-PCI TIMI 0/1, there was no effect of HD or LD on single
photon emission computed tomography infarct size or ejection fraction assessed at
Day 7 and Day 30. Subgroup analyses suggest that future work in patients with
anterior MI might be warranted. CONCLUSION: This first human experience with
caldaret prior to direct PCI for large STEMI shows a good safety profile. No
evidence of efficacy was discerned. Subgroup analyses in anterior MI patients
showed some effects in endpoints studied, however, these findings require
confirmation in a further study if a drug effect is to be established.
PMID- 17030522
TI - Subclinical atherosclerosis of lower limb arteries: a strong predictor for
cardiovascular mortality.
PMID- 17030523
TI - Outcome of implantable cardioverter defibrillators in adults with congenital
heart disease: a multi-centre study.
AB - AIMS: To investigate outcome and complications of implantable cardioverter
defibrillators (ICDs) in adults with congenital heart disease (CHD) and to
identify predictors of (in-) appropriate shocks. METHODS AND RESULTS: Sixty-four
CHD patients >/= 18 years at first ICD implantation [63% tetralogy of Fallot
(TOF) and age at implantation 37 +/- 13 years] were identified using the Dutch
adult CHD registry and a Belgian tertiary care centre database. Median follow-up
duration was 3.7 years. Early complications included pocket haematoma (n = 3),
lead failure (n = 2), and pneumothorax (n = 2). Late complications occurred in 11
(17%) patients, including lead failure (n = 6) and and electrical storm (n = 3).
Overall, 30 device-related re-interventions were performed in 20 patients (31%),
including four premature generator changes and seven lead replacements. Half of
the patients received one or more shocks, and 46 shocks in 15 patients (23%) were
classified as appropriate. One hundred and sixty shocks in 26 patients (41%) were
classified as inappropriate. No predictors of (in-)appropriate shocks were
identified, except TOF being associated with less appropriate shocks than
patients with other CHD (HR 0.29, P = 0.02). CONCLUSION: The ICD provided
effective therapy in a quarter of adults with CHD with low complication rates.
The incidence of inappropriate shocks, however, appeared to be excessive and
warrants further attention.
PMID- 17030524
TI - Prognostic role of combination of coronary flow reserve with aortic
distensibility indices.
PMID- 17030525
TI - Factors associated with HIV sero-positivity in young, rural South African men.
AB - OBJECTIVE: To describe factors associated with HIV infection in men aged 15-26
years. SETTING: Rural Eastern Cape Province, South Africa. SAMPLE: A total of
1277 sexually experienced Xhosa male volunteers from 70 villages participating in
a cluster randomized controlled trial of an HIV behavioural intervention. Xhosas
circumcise during manhood initiation rituals. DESIGN: Cross-sectional, analysis
of the study's baseline interviews. MAIN MEASURE: HIV sero-status, sexual
practices measured with an interviewer-administered questionnaire. RESULTS: About
2% of the men were HIV positive. A logistic regression model showed HIV
positivity to be associated with age (OR 1.55; 95%CI 1.22-1.95), having made a
woman pregnant (OR 2.93; 95% CI 1.28-6.68), having been circumcised (OR 0.40; 95%
CI 0.16-0.98), and having had sex with a man (OR 3.61; 95% CI 1.0-13.0).
CONCLUSIONS: Our findings provide further evidence to suggest that circumcision
is protective. There was much heterosexual risk taking among men but only
pregnancy (with its association with sexual frequency) predicted HIV sero
positivity. Although relatively rare, same-sex sexual experiences were a risk
factor. Male-male sexual contact is rarely assessed in HIV research in Africa and
almost never addressed in general HIV prevention programming. Our findings
suggest that it should be given more attention.
PMID- 17030526
TI - Child routines and youths' adherence to treatment for type 1 diabetes.
AB - OBJECTIVE: Type 1 diabetes (T1DM) is a chronic life-threatening disease that
requires strict adherence to daily treatment tasks. Although necessary for
survival, children who present with behavior problems tend to show problems
complying with the treatment regimen, thereby increasing their risk for morbidity
and premature mortality. The risk of poor treatment adherence is hypothesized to
be lower for these children, however, if they engage in more routine behaviors.
Given the potential clinical implications, this hypothesis and two theoretical
models proposed to elucidate the underlying psychological process for the role of
child routines in treatment adherence were evaluated empirically. The first model
hypothesized that child routines protect (moderator variable) behaviorally
problematic children from poor treatment adherence, whereas the alternative model
hypothesized that child routines mediate the relation between childhood behavior
problems and poor treatment adherence. METHODS: Parents of T1DM patients (N =
111) ranging from 6 to 16 years of age (M = 12 years) reported on their child's
behavior problems, routine behaviors, and adherence to treatment for T1DM using
standardized measures. Baron and Kenny's statistical procedures for testing
moderation and mediation hypotheses were used to evaluate the proposed models.
RESULTS: Regression analyses did not support the moderation hypothesis but did
support the hypothesis that engaging in child routines mediates the relation
between childhood behavior problems and poor treatment adherence. CONCLUSIONS:
Parents of behaviorally problematic children diagnosed with T1DM might be advised
to instill routines in their child's daily activities to increase the likelihood
of treatment adherence, and thereby reduce the risk of morbidity and early
mortality. Implications for clinical interventions are discussed.
PMID- 17030528
TI - Escalating polypharmacy.
AB - New drug treatments, new indications for older drug treatments, lower thresholds
for treating risk factors in preventative medicine, and an ageing population
acquiring multiple pathologies all contribute to the development of polypharmacy.
Longitudinal studies document the rise in prescribed medications, particularly in
the elderly. The potential dangers of adverse drug reactions and interactions,
poor adherence and confusion associated with ever-increasing polypharmacy are
likely to worsen. Strategies to reduce prescribing will obviously decrease the
dangers of polypharmacy. These include more considered prescribing when
contemplating additions to patients' already lengthy prescription lists, and
external reviews of medicine lists by a doctor or pharmacist. Despite such
strategies, polypharmacy seems inevitable and considerations must be given to
simplifying patients' multiple drug administrations using single-daily-dose
regimens, fixed-dose combination pills, calendar-blister packaging and pill
organizers.
PMID- 17030527
TI - Risk stratification for in-hospital mortality in spontaneous intracerebral
haemorrhage: a Classification and Regression Tree analysis.
AB - BACKGROUND: Risk stratification for mortality in intracerebral haemorrhage (ICH)
helps guide care, but existing clinical prediction rules are too cumbersome for
clinical practice because of their complexity. AIM: To develop a simple decision
tree model of in-hospital mortality risk stratification for ICH patients.
METHODS: We collected information on spontaneous ICH patients hospitalized in a
teaching hospital in Japan from August, 1998 to December, 2001 (n = 374). All
variables were abstracted from data available at the time of initial evaluation.
A prediction rule for in-hospital mortality was developed by the Classification
and Regression Tree (CART) methodology. The accuracy of the model was evaluated
using the area under receiver-operator characteristic curve. RESULTS: Overall in
hospital mortality rate was 20.2%. The CART methodology identified four groups
for mortality risk, varying from low (2.1%) to high (58.9%). Level of
consciousness (coma) was the best single predictor for mortality, followed by
high ICH volume (cut-off 10.4 ml), and then age (cut-off 75 years). The accuracy
of our CART model (0.86) exceeded that of a multivariate logistic regression
model (0.81). DISCUSSION: ICH patients can easily be stratified for mortality
risk, based on three predictors available on admission. This simple decision tree
model provides clinicians with a reliable and practical tool.
PMID- 17030529
TI - A simple score for assessing stable chronic obstructive pulmonary disease.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is usually assessed
using FEV(1) to establish the diagnosis and the severity of the disease. However,
COPD is now considered a systemic disease. AIM: To evaluate the utility of the
Health-Activity-Dyspnoea-Obstruction (HADO) score for classifying the severity of
COPD and predicting outcomes. DESIGN: Prospective longitudinal clinical study.
METHODS: We studied 611 consecutive patients with stable COPD in five out-patient
clinics of a teaching hospital. We measured dyspnoea degree, pulmonary function
(by spirometry), self-reported level of daily physical activity and overall
health condition. Outcome measures included health-related quality of life
(HRQoL) parameters (as measured by the generic SF-36 Health Survey and by two
specific questionnaires, the St George Respiratory Questionnaire and the Chronic
Respiratory Questionnaire) and mortality at 3 years follow-up. RESULTS: Based on
the HADO score, COPD was classified as mild in 26.7% of patients, moderate in
53.3%, and severe in 20%. There were statistically significant correlations
between these three levels of severity and HRQoL parameters and vital status.
After adjustment for relevant covariates, the HADO score reliably predicted
survival and vital status. DISCUSSION: The HADO score can be easily obtained in
an out-patient clinic, and distinguishes groups of COPD patients by their disease
severity. The HADO score is better than FEV(1%) alone for predicting mortality at
3 years.
PMID- 17030531
TI - Report of a case of congenital malaria Plasmodium malariae in France.
AB - Congenital malaria (CM) has been considered to be rare, even in malaria-endemic
areas but the disease can result in significant neonatal morbidity. Because of
its rarity, the disease may go undiagnosed for a prolonged period in a seriously
ill infant. We report the first case of Plasmodium malariae CM from a HIV mother.
HIV could have facilitated the transfer of erythrocytic persistent P. malariae
through the placenta to the fetus.
PMID- 17030532
TI - Randomized controlled trial of 7-Day vs. 14-Day antibiotics for neonatal sepsis.
AB - There are no evidence-based guidelines available regarding the duration of
antibiotics in neonatal septicemia. We compared the effectiveness of a 7-day
intravenous antibiotic regimen with the standard 14-day regime in blood-culture
proven sepsis in neonates. This was a controlled, blinded, randomized trial with
stratification (for birth weight). Blood-culture-positive septic babies > or =32
weeks and/or > or =1500 g were enrolled if meningitis and other deep-seated focal
infections were ruled out. Parental consent was obtained. Randomization to either
7-day or 14-day therapy was done on day 7 of antibiotics if the baby had
clinically remitted by day 5. Blood culture was repeated 24 h after antibiotic
completion. Subjects were observed in the hospital for at least 72 h, and
followed-up for 28 days by weekly visits and telephonic contacts. The primary
outcome was treatment failure within 28 days defined as a positive blood culture,
or clinical signs accompanied by either positive CRP or adjudicated to be a
relapse by an expert committee. A total of 120 babies were eligible, 51 were
excluded (no consent: 12; non-remission: 39), and 69 were randomized to receive
either a 7-day course (n = 34) or a 14-day course (n = 35) of antibiotics.
Baselines variables were comparable in the two groups. Primary outcome assessment
could be done in 33 cases in either group. There was a trend to greater treatment
failures in the 7-day group compared with 14-day group (5 vs. 1, respectively; P
= 0.19). On subgroup analysis of subjects with Staphylococcus aureus infection,
those who received 7-day therapy (n = 7) had significantly more treatment failure
than 14-day therapy (n = 7) (four and zero, respectively; P = 0.022), whereas on
sub-group analysis of babies with non-S. aureus infections, treatment failure
rates were identical (3.8% in both groups). On comparing the organisms isolated
in the group of subjects which was not randomized by virtue of being symptomatic
(n = 39) vs. the group which was randomized (n = 69), it was found that S. aureus
infections were significantly commoner in the former group (61.5 vs. 21.3%,
respectively; P < 0.001). Neonates > or =32 weeks and/or > or =1500 g with S.
aureus sepsis require 14 days of antibiotics. S. aureus infection is also
associated with failure to achieve clinical remission by the 5th day of
antibiotic therapy. Larger trials are required to confirm whether neonates with
non-S. aureus sepsis, whose symptoms remit by 5 days, can be treated with 7 days
of antibiotics.
PMID- 17030533
TI - Could nutritional rehabilitation at home complement or replace centre-based
therapeutic feeding programmes for severe malnutrition?
AB - To measure the success rate of three different strategies used in Medecins Sans
Frontieres large-scale therapeutic nutritional rehabilitation programme in Niger,
we analysed three cohorts of severely malnourished patients in terms of daily
weight gain, length of stay, recovery, case fatality and defaulting. A total of
1937 children aged 6-59 months were followed prospectively from 15 August 2002 to
21 October 2003. For the three cohorts, 660 children were maintained in the
therapeutic feeding centre (TFC) during the entire treatment, 937 children were
initially treated at the TFC and completed treatment at home and 340 children
were exclusively treated at home. For all cohorts, average time in the programme
and average weight gain met the international standards (30-40 days, >8
g/kg/day). Default rates were 28.1, 16.8 and 5.6% for TFC only, TFC plus home
based and home-based alone strategies, respectively. The overall case fatality
rate for the entire programme was 6.8%. Case fatality rates were 18.9% for TFC
only and 1.7% for home-based alone. No deaths were recorded in children
transferred to rehabilitation at home. This study suggests that satisfactory
results for the treatment of severe malnutrition can be achieved using a
combination of home and hospital-based strategies.
PMID- 17030534
TI - Novel splicing mutation in the progranulin gene causing familial corticobasal
syndrome.
AB - Corticobasal syndrome (CBS) is a rare cognitive and movement disorder
characterized by asymmetric rigidity, apraxia, alien-limb phenomenon, cortical
sensory loss, myoclonus, focal dystonia, and dementia. It occurs along the
clinical spectrum of frontotemporal lobar degeneration (FTLD), which has recently
been shown to segregate with truncating mutations in progranulin (PGRN), a
multifunctional growth factor thought to promote neuronal survival. This study
identifies a novel splice donor site mutation in the PGRN gene (IVS7+1G-->A) that
segregates with CBS in a Canadian family of Chinese origin. We confirmed the
absence of the mutant PGRN allele in the RT-PCR product which supports the model
of haploinsufficiency for PGRN-linked disease. This report of mutation in the
PGRN gene in CBS extends the evidence for genetic and phenotypic heterogeneity in
FTLD spectrum disorders.
PMID- 17030536
TI - The quest for florigen: a review of recent progress.
AB - The photoperiodic induction of flowering is a systemic process requiring
translocation of a floral stimulus from the leaves to the shoot apical meristem.
In response to this stimulus, the apical meristem stops producing leaves to
initiate floral development; this switch in morphogenesis involves a change in
the identity of the primordia initiated and in phyllotaxis. The physiological
study of the floral transition has led to the identification of several putative
floral signals such as sucrose, cytokinins, gibberellins, and reduced N-compounds
that are translocated in the phloem sap from leaves to the shoot apical meristem.
On the other hand, the genetic approach developed more recently in Arabidopsis
thaliana allowed the discovery of many genes that control flowering time. These
genes function in 'cascades' within four promotive pathways, the 'photoperiodic',
'autonomous', 'vernalization', and 'gibberellin' pathways, which all converge on
the 'integrator' genes SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1) and FLOWERING
LOCUS T (FT). Recently, several studies have highlighted a role for a product of
FT as a component of the floral stimulus or 'florigen'. These recent advances and
the proposed mode of action of FT are discussed here.
PMID- 17030535
TI - Frontotemporal dementia and parkinsonism associated with the IVS1+1G->A mutation
in progranulin: a clinicopathologic study.
AB - We previously reported a kindred with three cases of dementia, in which the
proband exhibited features typical of frontotemporal dementia and parkinsonism
(FTDP). An arginine insertion at codon 352 (insR352) in the presenilin-1 (PSEN1)
gene was identified in the proband, but analyses in plasma and CSF suggested a
mechanism of neurodegeneration not directly related to amyloid pathophysiology.
The proband was followed with yearly evaluations of functional, clinical,
neuropsychologic, neuropsychiatric and radiologic status, which showed relatively
linear change over the initial 4 years of assessment. Upon the proband's death at
age 63, neuropathologic examination revealed frontotemporal lobar degeneration
(FTLD) with ubiquitin-positive inclusions (FTLD-U). We recently identified
several kindreds with familial FTDP associated with mutations in the progranulin
(PGRN) gene, particularly in those cases with neuronal intranuclear inclusions.
Our proband was indeed found to have such inclusions, and PGRN analysis in this
proband revealed the G to A mutation in the exon 1 splice donor site (IVS1+1G-
>A) which is predicted to destroy the 5'-splice site of exon 1 and remove the
start methionine codon and hence completely block any PGRN protein from being
generated. These findings suggest that the insR352 PSEN1 is not pathogenic, and
the IVS1+1G-->A mutation in PGRN causes FTDP associated with FTLD-U pathology and
represents a new class of neurodegenerative disease--the
'hypoprogranulinopathies'.
PMID- 17030537
TI - Respiratory carbon metabolism in the high mountain plant species Ranunculus
glacialis.
AB - Very little is known about the primary carbon metabolism of the high mountain
plant Ranunculus glacialis. It is a species with C3 photosynthesis, but with
exceptionally high malate content in its leaves, the biological significance of
which remains unclear. 13C/12C-isotope ratio mass spectrometry (IRMS) and 13C
nuclear magnetic resonance (NMR) labelling were used to study the carbon
metabolism of R. glacialis, paying special attention to respiration. Although
leaf dark respiration was high, the temperature response had a Q10 of 2, and the
respiratory quotient (CO2 produced divided by O2 consumed) was nearly 1,
indicating that the respiratory pool is comprised of carbohydrates. Malate, which
may be a large carbon substrate, was not respired. However, when CO2 fixed by
photosynthesis was labelled, little labelling of the CO2 subsequently respired in
the dark was detected, indicating that: (i) most of the carbon recently
assimilated during photosynthesis is not respired in the dark; and (ii) the
carbon used for respiration originates from (unlabelled) reserves. This is the
first demonstration of such a low metabolic coupling of assimilated and respired
carbon in leaves. The biological significance of the uncoupling between
assimilation and respiration is discussed.
PMID- 17030538
TI - Compartmentation in plant metabolism.
AB - Cell fractionation and immunohistochemical studies in the last 40 years have
revealed the extensive compartmentation of plant metabolism. In recent years, new
protein mass spectrometry and fluorescent-protein tagging technologies have
accelerated the flow of information, especially for Arabidopsis thaliana, but the
intracellular locations of the majority of proteins in the plant proteome are
still not known. Prediction programs that search for targeting information within
protein sequences can be applied to whole proteomes, but predictions from
different programs often do not agree with each other or, indeed, with
experimentally determined results. The compartmentation of most pathways of
primary metabolism is generally covered in plant physiology textbooks, so the
focus here is mainly on newly discovered metabolic pathways in plants or pathways
that have recently been revised. Ultimately, all of the pathways of plant
metabolism are interconnected, and a major challenge facing plant biochemists is
to understand the regulation and control of metabolic networks. One of the best
characterized networks links sucrose synthesis in the cytosol with photosynthetic
CO(2) fixation and starch synthesis in the chloroplasts. One of the key features
of this network is how the transport of pathway intermediates and signal
metabolites across the chloroplast envelope conveys information between the two
compartments, influencing the regulation of several enzymes to co-ordinate fluxes
through the different pathways. It is widely accepted that chloroplasts and
mitochondria originated from prokaryotic endosymbionts, and that new transporters
and regulatory networks evolved to integrate metabolism in these organelles with
the rest of the cell. Curiously, the present-day locations of many metabolic
pathways within the cell often do not reflect their evolutionary origin, and
there is evidence of extensive shuffling of enzymes and whole pathways between
compartments during the evolution of plants.
PMID- 17030539
TI - Developmental regulation of a VEIDase caspase-like proteolytic activity in barley
caryopsis.
AB - Caspases are essential in animal programmed cell death both as initiator and
executioner proteases. Plants do not have close caspase homologues, but several
instances of caspase-like proteolytic activity have been demonstrated in
connection with programmed cell death in plants. It was asked if caspase-like
proteases are involved during development of the barley caryopsis. The presence
of a caspase-6-like proteolytic activity that preferentially cleaved the sequence
VEID was demonstrated. A range of protease inhibitors was tested and only caspase
specific inhibitors showed major inhibitory effects. The profile of VEIDase
activity in developing starchy endosperm, embryo, and whole caryopsis was
measured and showed a general trend of higher activity in young, rapidly
developing tissues. The VEIDase activity was localized in vivo to vesicles, shown
to be autophagosomes, in randomly distributed cells of the starchy endosperm. The
VEIDase activity detected in barley caryopsis is similar to activities described
previously in mammals, spruce, yeast, and thale cress. In mammals, spruce, and
yeast, VEIDase activity has been shown to be positively correlated with the
occurrence of programmed cell death. Several manifestations of programmed cell
death exist in developing barley caryopsis, indicating a connection between
VEIDase activity and developmental programmed cell death in barley.
PMID- 17030540
TI - 3D lidar imaging for detecting and understanding plant responses and canopy
structure.
AB - Understanding and diagnosing plant responses to stress will benefit greatly from
three-dimensional (3D) measurement and analysis of plant properties because plant
responses are strongly related to their 3D structures. Light detection and
ranging (lidar) has recently emerged as a powerful tool for direct 3D measurement
of plant structure. Here the use of 3D lidar imaging to estimate plant properties
such as canopy height, canopy structure, carbon stock, and species is
demonstrated, and plant growth and shape responses are assessed by reviewing the
development of lidar systems and their applications from the leaf level to canopy
remote sensing. In addition, the recent creation of accurate 3D lidar images
combined with natural colour, chlorophyll fluorescence, photochemical reflectance
index, and leaf temperature images is demonstrated, thereby providing information
on responses of pigments, photosynthesis, transpiration, stomatal opening, and
shape to environmental stresses; these data can be integrated with 3D images of
the plants using computer graphics techniques. Future lidar applications that
provide more accurate dynamic estimation of various plant properties should
improve our understanding of plant responses to stress and of interactions
between plants and their environment. Moreover, combining 3D lidar with other
passive and active imaging techniques will potentially improve the accuracy of
airborne and satellite remote sensing, and make it possible to analyse 3D
information on ecophysiological responses and levels of various substances in
agricultural and ecological applications and in observations of the global
biosphere.
PMID- 17030541
TI - Horizontal gene transfer in plants.
AB - Horizontal gene transfer (HGT) has played a major role in bacterial evolution and
is fairly common in certain unicellular eukaryotes. However, the prevalence and
importance of HGT in the evolution of multicellular eukaryotes remain unclear.
Recent studies indicate that plant mitochondrial genomes are unusually active in
HGT relative to all other organellar and nuclear genomes of multicellular
eukaryotes. Although little about the mechanisms of plant HGT is known, several
studies have implicated parasitic plants as both donors and recipients of
mitochondrial genes. Most cases uncovered thus far have involved a single
transferred gene per species; however, recent work has uncovered a case of
massive HGT in Amborella trichopoda involving acquisition of at least a few dozen
and probably hundreds of foreign mitochondrial genes. These foreign genes came
from multiple donors, primarily eudicots and mosses. This review will examine the
implications of such massive transfer, the potential mechanisms and consequences
of plant-to-plant mitochondrial HGT in general, as well as the limited evidence
for HGT in plant chloroplast and nuclear genomes.
PMID- 17030542
TI - ABP1 expression regulated by IAA and ABA is associated with the cambium
periodicity in Eucommia ulmoides Oliv.
AB - A cDNA clone of Eucommia ulmoides Oliv. encoding auxin binding protein 1 (ABP1),
one of the putative receptors of auxin, was isolated, and the seasonal expression
of ABP1 in relation to IAA and ABA annual variation was investigated by different
technical approaches including RT-PCR, real-time PCR, northern blotting, western
blotting, and immunolocalization. In the cambial region, ABP1 expression at both
the protein and the mRNA level was found to be high, low, and remarkably scarce
in the active, quiescent, and resting stages, respectively, during cambium
periodicity. The signal abundance of ABP1 follows the opposite pattern to ABA
accumulation and correlates with auxin responsiveness of the cambial tissues,
suggesting a role for ABP1 in mediating auxin-dependent regulation of cambial
activation in the activity-dormancy cycle. This paper attempts to explain why IAA
would 'boost' the reactivation of a quiescent cambium, and not that of a resting
cambium. Results also show that ABP1 expression is improved by IAA, while
inhibited by ABA.
PMID- 17030543
TI - Clinical benefit of fulvestrant in postmenopausal women with advanced breast
cancer and primary or acquired resistance to aromatase inhibitors: final results
of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00).
AB - BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability
of fulvestrant, an estrogen receptor antagonist, in postmenopausal women with
hormone-responsive tumors progressing after aromatase inhibitor (AI) treatment.
PATIENTS AND METHODS: This is a phase II, open, multicenter, noncomparative
study. Two patient groups were prospectively considered: group A (n=70) with AI
responsive disease and group B (n=20) with AI-resistant disease. Fulvestrant 250
mg was administered as intramuscular injection every 28 (+/-3) days. RESULTS: All
patients were pretreated with AI and 84% also with tamoxifen or toremifene; 67%
had bone metastases and 45% liver metastases. Fulvestrant administration was well
tolerated and yielded a clinical benefit (CB; defined as objective response or
stable disease [SD] for >or=24 weeks) in 28% (90% confidence interval [CI] 19% to
39%) of patients in group A and 37% (90% CI 19% to 58%) of patients in group B.
Median time to progression (TTP) was 3.6 (95% CI 3.0 to 4.8) months in group A
and 3.4 (95% CI 2.5 to 6.7) months in group B. CONCLUSIONS: Overall, 30% of
patients who had progressed following prior AI treatment gained CB with
fulvestrant, thereby delaying indication to start chemotherapy. Prior response to
an AI did not appear to be predictive for benefit with fulvestrant.
PMID- 17030544
TI - Palifermin (recombinant keratinocyte growth factor-1): a pleiotropic growth
factor with multiple biological activities in preventing chemotherapy- and
radiotherapy-induced mucositis.
AB - Oral and intestinal mucositis are among the most significant dose-limiting toxic
effects of intensive cancer treatment and are associated with adverse clinical
and economic outcomes. Palifermin (Kepivancetrade mark), an N-truncated
recombinant human keratinocyte growth factor-1, is the first agent to be approved
for prevention of oral mucositis. Keratinocyte growth factor, a potent epithelial
mitogen, appears to play a major role in the healing process. Palifermin has
multiple biological activities that appear to protect the mucosal epithelium and
promote its early regeneration after irradiation- and chemotherapy-induced
injury. These include inhibition of epithelial cell apoptosis and DNA damage, up
regulation of detoxifying enzymes and down-regulation of pro-inflammatory
cytokines, as well as enhanced migration, proliferation and differentiation of
epithelial cells. Palifermin reduces the incidence, severity and duration of oral
mucositis in patients with haematological malignancies undergoing myelotoxic
conditioning therapy and haematopoietic stem-cell transplantation. Clinical
sequelae, including febrile neutropenia and resource use (opioid analgesia and
parenteral feeding), are concomitantly reduced. Other potential applications
being explored include use in the solid tumour setting, reduction of intestinal
mucositis and reduction of GVHD in allogenic transplantation. Thus, the
development of palifermin and other potential new agents for preventing
chemotherapy- and radiotherapy-induced mucositis represents an important
breakthrough in oncological supportive care.
PMID- 17030545
TI - Late risk of relapse and mortality among postmenopausal women with estrogen
responsive early breast cancer after 5 years of tamoxifen.
AB - BACKGROUND: Letrozole after 5 years of adjuvant tamoxifen results in a
significant reduction in risk of recurrence from estrogen receptor (ER) positive
breast cancer. An individualized estimate of the risk of relapse and death after
5 years of tamoxifen could improve decisions regarding extended hormonal therapy.
METHODS: The British Columbia Breast Cancer Outcomes database was used to
identify women aged 45 years or older at the time of diagnosis with early-stage
(I-IIIA) breast cancer who received tamoxifen and were disease free 5 years after
diagnosis. Ten-year breast cancer event rates and mortality were calculated as
well as annualized hazard rates of recurrence. RESULTS: A total of 1086 women
were identified with a median age of 64 years and follow-up of 10.5 years. The
relative risk (RR) of death was 3.1 (P=0.003) and for recurrence was 1.7
(P=0.037) for N1 (one to three positive nodes) versus N0 (zero nodes positive)
disease. N2 (four to nine nodes positive) had a RR of 5.8 (P<0.001) for death and
3.0 (P=0.002) for recurrence. Low tumor grade and high ER level subgroups had a
more favorable prognosis. Annual breast cancer risk between years 6 and 10 was,
respectively, 2.2%, 3.5% and 7.6% for N0, N1 and N2 disease and 2.6% and 4.5% for
T1 and T2 breast cancer. CONCLUSION: T and N stages predicted late relapse and
death from breast cancer in a population-based cohort of postmenopausal women.
Risk estimates reported herein may be used to optimize decision making regarding
adjuvant therapy after 5 years of tamoxifen.
PMID- 17030546
TI - Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive
patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter
phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
AB - BACKGROUND: Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil
(5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse
effect profiles. This trial assessed efficacy and safety of the triple
combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally
advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma. PATIENTS AND
METHODS: A total of 43 eligible patients were treated with intravenous infusions
of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2
h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. RESULTS:
Among all 43 patients, the tumor response rate was 19% [95% confidence interval
7% to 30%]. Nine patients were nonassessable for response because they did not
complete the first two cycles of chemotherapy due to rapid disease progression,
early death or treatment refusal. One patient was lost to follow-up. Median time
to progression and overall survival were 5.7 and 7.5 months. Principal grade
III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%),
nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of
patients. Unexpected cardiotoxicity was observed in this trial. CONCLUSION:
Response rates and survival of the three-drug combination compare favorably with
single-agent gemcitabine, but do not exceed results for doublets.
PMID- 17030547
TI - Epidemiology of peritoneal mesothelioma: a review.
AB - The epidemiology of peritoneal mesothelioma is complicated by possible geographic
and temporal variations in diagnostic practices. The incidence rates in
industrialized countries range between 0.5 and three cases per million in men and
between 0.2 and two cases per million in women. Exposure to asbestos is the main
known cause of peritoneal mesothelioma. Results on peritoneal mesothelioma have
been reported for 34 cohorts exposed to asbestos, among which a strong
correlation was present between the percentages of deaths from pleural and
peritoneal mesothelioma (correlation coefficient 0.8, P < 0.0001). Studies of
workers exposed only or predominantly to chrysotile asbestos resulted in a lower
proportion of total deaths from peritoneal mesothelioma than studies of workers
exposed to amphibole or mixed type of asbestos. Cases of peritoneal mesothelioma
have also been reported following exposure to erionite and Thorotrast, providing
further evidence of common etiological factors with the pleural form of the
disease. The role of other suspected risk factors, such as simian virus 40
infection and genetic predisposition, is unclear at present. Control of asbestos
exposure remains the main approach to prevent peritoneal mesothelioma.
PMID- 17030548
TI - Phase II study of an optimized 5-fluorouracil-oxaliplatin strategy (OPTIMOX2)
with celecoxib in metastatic colorectal cancer: a GERCOR study.
AB - BACKGROUND: Oxaliplatin stop and go in combination with leucovorin and 5
fluorouracil has been successfully used in a previous study (OPTIMOX1) in
metastatic colorectal cancer (MCR). Celecoxib is an anti-cyclooxygenase-2 drug
with anti-neoplastic properties. In the present study, celecoxib was evaluated in
combination with FOLFOX7 regimen and as a single agent in maintenance therapy.
PATIENTS AND METHODS: This phase II study examined for previously untreated MCR
patients the stop-and-go procedure [six cycles of folinic acid, 5FU and
oxaliplatin (FOLFOX7) followed by chemotherapy-free intervals (CFIs) and
reintroduction at progression] with continuous administration of celecoxib (800
mg/day). RESULTS: Forty-four patients were included, 42 eligible: performance
status (%) 0/1/2=45/40/15, median age 60 (31-76) years. Response rate (RR) was
43% (95% CI 28%-58%). Median progression-free survival (PFS) was 6 months; median
overall survival was 15.8 months. Grade 3/4 toxicity criteria were neurotoxicity
9.5%, thrombocytopenia 21.4%, neutropenia 7.1%, diarrhea 7.1%, nausea 4.8% and
vomiting 2.4%. Median CFI 1 (n=27) duration was 3.9 months (range 2-39 months).
CONCLUSION: With an acceptable safety profile, celecoxib combined with FOLFOX7
achieved RR and PFS in the lower range of that obtained with FOLFOX7 alone. These
results indicate the lack of synergy between FOLFOX7 and celecoxib. PFS of 6
months appears lower than PFS obtained in OPTIMOX1 study with simplified LV5FU2
in maintenance therapy.
PMID- 17030549
TI - MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in
patients with bone metastases--preliminary clinical experience.
AB - BACKGROUND: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a
noninvasive thermal ablation technique, shown to be clinically effective in the
treatment of uterine fibroids and is being evaluated as a method of thermal
ablation of benign and malignant breast tumors. To evaluate the safety and
initial efficacy of MRgFUS for the palliation of pain caused by bone metastases,
in patients for whom other treatments are either not effective or not feasible.
MATERIALS AND METHODS: Thirteen patients suffering from symptomatic bone
metastases underwent MRgFUS procedure. Treatment safety was evaluated by
assessing the incidence and severity of device-related complications up to 6
months after treatment. Effectiveness of pain palliation was evaluated by visual
analog scale, pain questionnaires and changes in the patients' medication.
RESULTS: Fifteen procedures were carried out. Mean follow-up was 59 days. Twelve
patients received adequate treatment and were available for follow-up. Two
patients died due to disease progression during the first month after treatment.
No severe adverse events were recorded. The remaining 10 patients reported
prolonged improvement in pain score and/or reduced analgesic dosage. CONCLUSION:
MRgFUS may provide a safe and effective noninvasive alternative for the
palliation of pain, caused by bone metastases.
PMID- 17030550
TI - Health-related quality of life in disease-free survivors of breast cancer with
the general population.
AB - BACKGROUND: Although most of the literature about health-related quality of life
(HRQoL) focuses on breast cancer patients, few studies compared the HRQoL in
disease-free breast cancer survivors with that of the general population.
MATERIALS AND METHODS: We administered the European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire Core 30 and Quality of Life
Questionnaire Breast Cancer Module, McGill Quality of Life Questionnaire, Beck
Depression Inventory, and Brief Fatigue Inventory to 1933 disease-free survivors
for over 1 year after being diagnosed with stage 0 to III breast cancer. We
performed multivariate-adjusted analyses in all HRQoL comparisons. RESULTS: The
scores for some health-related quality of life [corrected] HRQoL scales were
comparable for both disease-free breast cancer survivors and the general female
population, but [corrected] there was a [corrected] clinically significant
difference between the two groups [corrected] in cognitive and social
functioning, fatigue, insomnia, financial difficulties, body image, future
perspective, breast symptoms, and arm symptoms. [corrected] CONCLUSIONS: Disease
free survivors of breast cancer had good HRQoL, which was less affected by the
type of treatment than it was by demographic characteristics, time since surgery,
comorbidity, fatigue, and depression.
PMID- 17030551
TI - Constructing socio-economic status indices: how to use principal components
analysis.
AB - Theoretically, measures of household wealth can be reflected by income,
consumption or expenditure information. However, the collection of accurate
income and consumption data requires extensive resources for household surveys.
Given the increasingly routine application of principal components analysis (PCA)
using asset data in creating socio-economic status (SES) indices, we review how
PCA-based indices are constructed, how they can be used, and their validity and
limitations. Specifically, issues related to choice of variables, data
preparation and problems such as data clustering are addressed. Interpretation of
results and methods of classifying households into SES groups are also discussed.
PCA has been validated as a method to describe SES differentiation within a
population. Issues related to the underlying data will affect PCA and this should
be considered when generating and interpreting results.
PMID- 17030552
TI - Who suffers from indoor air pollution? Evidence from Bangladesh.
AB - In this paper, we investigate individuals' exposure to indoor air pollution.
Using new survey data from Bangladesh, average hours spent by members of
households in the cooking area, living area and outdoors in a typical day are
combined with the estimates of pollution concentration in different locations in
order to estimate exposure. We analyse exposure at two levels: differences within
households attributable to family roles, and differences across households
attributable to income and education. Within households, we relate individuals'
exposure to pollution in different locations during their daily round of
activities. We find high levels of exposure for children and adolescents of both
sexes, with particularly serious exposure for children under 5 years. Among prime
age adults, we find that men have half the exposure of women (whose exposure is
similar to that of children and adolescents). We also find that elderly men have
significantly lower exposure than elderly women. Across households, we draw on
results from a previous paper, which relate pollution variation across households
to choices of cooking fuel, cooking locations, construction materials and
ventilation practices. We find that these choices are significantly affected by
family income and adult education levels (particularly for women). Overall, we
find that the poorest, least-educated households have twice the pollution levels
of relatively high-income households with highly educated adults. Our findings
further suggest that young children and poorly educated women in poor households
face pollution exposures that are four times those for men in higher income
households organized by more highly educated women. Since infants and young
children suffer the worst mortality and morbidity from indoor air pollution, in
this paper we consider measures for reducing their exposure. Our recommendations
for reducing the exposure of infants and young children are based on a few
simple, robust findings. Hourly pollution levels in cooking and living areas are
quite similar because cooking smoke diffuses rapidly and nearly completely into
living areas. However, outdoor pollution is far lower. At present, young children
are only outside for an average of 3 hours per day. For children in a typical
household, pollution exposure can be halved by adopting two simple measures:
increasing their outdoor time from 3 to 5 or 6 hours per day, and concentrating
outdoor time during peak cooking periods.
PMID- 17030553
TI - Phytolith assemblages and systematic associations in grassland species of the
South-eastern Pampean plains, Argentina.
AB - BACKGROUND AND AIMS: Phytolith descriptions of South American plant species are
scarce. This knowledge is crucial for the interpretation of the fossil phytolith
record of a region. In this study phytolith assemblages and systematic
relationships of the main grasses and Asteraceae species of Paspalum quadrifarium
grassland are described. METHODS: Phytoliths from leaves of Poaceae and
Asteraceae species were extracted by using a calcination technique. For each
species, 350-400 phytoliths were counted and the relative frequency of each
morphotype was calculated. Phytolith assemblages were subject to principal
components analysis (PCA) and cluster analysis (Morisita index). KEY RESULTS: PCA
and cluster analysis showed family (Poaceae vs. Asteraceae) and subfamily (within
Poaceae) differentiation. Exceptions to general trends described for other
species were detected. Floristic variants of Paspalum quadrifarium grassland can
be separated by their phytolith assemblages. CONCLUSIONS: The study provides a
reference collection of phytolith assemblages of the main Poaceae and Asteraceae
species of Paspalum quadrifarium grassland and describes some phytolith
morphotypes/systematic relationships useful for the analysis of fossil phytolith
assemblages of the Pampean region.
PMID- 17030554
TI - Haplotypes spanning SPEC2, PDZ-GEF2 and ACSL6 genes are associated with
schizophrenia.
AB - Chromosome 5q22-33 is a region where studies have repeatedly found evidence for
linkage to schizophrenia. In this report, we took a stepwise approach to
systematically map this region in the Irish Study of High Density Schizophrenia
Families (ISHDSF, 267 families, 1337 subjects) sample. We typed 289 SNPs in the
critical interval of 8 million basepairs and found a 758 kb interval coding for
the SPEC2/PDZ-GEF2/ACSL6 genes to be associated with the disease. Using sex and
genotype-conditioned transmission disequilibrium test analyses, we found that 19
of the 24 typed markers were associated with the disease and the associations
were sex-specific. We replicated these findings with an Irish case-control sample
(657 cases and 414 controls), an Irish parent-proband trio sample (187 families,
564 subjects), a German nuclear family sample (211 families, 751 subjects) and a
Pittsburgh nuclear family sample (247 families, 729 subjects). In all four
samples, we replicated the sex-specific associations at the levels of both
individual markers and haplotypes using sex- and genotype-conditioned analyses.
Three risk haplotypes were identified in the five samples, and each haplotype was
found in at least two samples. Consistent with the discovery of multiple estrogen
response elements in this region, our data showed that the impact of these
haplotypes on risk for schizophrenia differed in males and females. From these
data, we concluded that haplotypes underlying the SPEC2/PDZ-GEF2/ACSL6 region are
associated with schizophrenia. However, due to the extended high LD in this
region, we were unable to distinguish whether the association signals came from
one or more of these genes.
PMID- 17030555
TI - Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats:
toxicity is not dependent upon particle size but on surface characteristics.
AB - Pulmonary toxicology studies in rats demonstrate that nanoparticles are more
toxic than fine-sized particles of similar chemistry. This study, however,
provides evidence to contradict this theory. The aims of the study were (1) to
compare the toxicity of synthetic 50 nm nanoquartz I particles versus (mined) Min
U-Sil quartz ( approximately 500 nm); the toxicity of synthetic 12 nm nanoquartz
II particles versus (mined) Min-U-Sil ( approximately 500 nm) versus (synthetic)
fine-quartz particles (300 nm); and (2) to evaluate the surface activities among
the samples as they relate to toxicity. Well-characterized samples were tested
for surface activity and hemolytic potential. In addition, groups of rats were
instilled with either doses of 1 or 5 mg/kg of carbonyl iron (CI) or various
alpha-quartz particle types in phosphate-buffered saline solution and
subsequently assessed using bronchoalveolar lavage fluid biomarkers, cell
proliferation, and histopathological evaluation of lung tissue at 24 h, 1 week, 1
month, and 3 months postexposure. Exposures to the various alpha-quartz particles
produced differential degrees of pulmonary inflammation and cytotoxicity, which
were not always consistent with particle size but correlated with surface
activity, particularly hemolytic potential. Lung tissue evaluations of three of
the quartz samples demonstrated "typical" quartz-related effects--dose-dependent
lung inflammatory macrophage accumulation responses concomitant with early
development of pulmonary fibrosis. The various alpha-quartz-related effects were
similar qualitatively but with different potencies. The range of particle-related
toxicities and histopathological effects in descending order were nanoscale
quartz II = Min-U-Sil quartz > fine quartz > nanoscale quartz I > CI particles.
The results demonstrate that the pulmonary toxicities of alpha-quartz particles
appear to correlate better with surface activity than particle size and surface
area.
PMID- 17030556
TI - Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells.
AB - The taste system, made up of taste receptor cells clustered in taste buds at the
surface of the tongue and the soft palate, plays a key role in the decision to
ingest or reject food and thereby is essential in protecting organisms against
harmful toxins and in selecting the most appropriate nutrients. To determine if a
similar chemosensory system exists in the gastrointestinal tract, we used
immunohistochemistry and real-time polymerase chain reaction (PCR) to investigate
which taste-signaling molecules are expressed in the intestinal mucosa. The PCR
data showed that T1r1, T1r2, T1r3, alpha-gustducin, phospholipase Cbeta2
(PLCbeta2), and Trpm5 are expressed in the stomach, small intestine, and colon of
mice and humans, with the exception of T1r2, which was not detected in the mouse
and human stomach or in the mouse colon. Using transgenic mice expressing
enhanced green fluorescent protein under the control of the Trpm5 promoter, we
found colocalization of Trpm5 and alpha-gustducin in tufted cells at the surface
epithelium of the colon, but these cells did not express T1r3 or PLCbeta2. In the
duodenal glands, 43%, 33%, and 38% of Trpm5-expressing cells also express
PLCbeta2, T1r3, or alpha-gustducin, respectively. The duodenal gland cells that
coexpress PLCbeta2 and Trpm5 morphologically resemble enteroendocrine cells. We
found a large degree of colocalization of Trpm5, alpha-gustducin, T1r1, and T1r3
in tufted cells of the duodenal villi, but these cells rarely expressed PLCbeta2.
The data suggest that these duodenal cells are possibly involved in sensing amino
acids.
PMID- 17030557
TI - Determinants of neuropsychological and behavioural outcomes in early childhood
survivors of congenital heart disease.
AB - AIMS: To evaluate the relative effect of cyanosis, surgical interventions and
family processes on neuropsychological and behavioural outcomes in 4-year-old
survivors of serious congenital heart disease (CHD). METHODS: 90 children with a
range of cyanotic and acyanotic conditions, who underwent either corrective or
palliative surgery, completed a neuropsychological and behavioural evaluation.
Families of participants were also profiled by evaluation of maternal mental
health, worry, social support, parenting style and family functioning. RESULTS:
Compromised neuropsychological outcomes were associated with a combination of
cyanotic conditions and open-heart surgery, but this was not exacerbated by
having a complex, palliative, status. Both cyanotic and acyanotic conditions were
associated with specific sensorimotor delays, regardless of method of the
correction. Only children with complex conditions and palliative interventions
seemed at risk of poor behavioural outcomes; indeed, children with cyanosis with
complete repair showed favourable behavioural outcomes compared with controls.
Multivariate analyses highlighted the sometimes greater relevance of family
processes (eg parenting style, maternal mental health and worry), rather than
disease or surgical factors, in predicting especially behavioural outcomes.
CONCLUSIONS: The findings (1) suggest a more complex relationship between
cyanosis, surgical methods of correction, neuropsychological and behavioural
outcomes than previously charted, (2) highlight that family processes may be
aetiologically more important than disease and surgical factors, and (3) indicate
specific targets for secondary prevention programmes for this at-risk population.
PMID- 17030558
TI - Landmarks in understanding the central nervous control of the cardiovascular
system.
AB - In this Paton Lecture I have tried to trace the key experiments that have
developed ideas on how the brain regulates the cardiovascular system. It is a
personal view and inevitably, owing to constraints on space and time, I have not
been able to cover areas such as the nucleus tractus solitarius and cardiac vagal
neurones, although I acknowledge that some may consider the story is incomplete
without them. Starting with the crucial discovery of vasomotor nerves and
'vasomotor tone', the patterns of activity in sympathetic nerves which led to the
important idea of central oscillating networks of neurones are described. I
discuss how this knowledge has informed current controversies on the origin of
vasomotor activity in presympathetic neurones in the ventral medulla, which
identify intrinsic pacemaker activity or synaptic input from multiple oscillators
as prime mechanisms. I present an emerging view that the role of other regions of
the brain, in particular supramedullary sites, has been underplayed. These
regions are pivotal for the non-uniform distribution of cardiac output that is
unique to each reflex and behavioural state. I discuss the most recent evidence
for 'central command' neurones that offers a plausible explanation for how these
patterns of sympathetic activity are achieved. Finally, I stress the importance
of these current ideas to the understanding of pathological changes in
sympathetic activity in cardiovascular diseases such as hypertension or
congestive heart failure.
PMID- 17030559
TI - Differential regulation of the nitric oxide-cGMP pathway exacerbates
postischaemic heart injury in stroke-prone hypertensive rats.
AB - Using a working perfused heart model, we investigated the hypothesis that
alterations in the NO-cGMP pathway may exacerbate postischaemic mechanical
dysfunction in the hypertrophied heart. Ischaemia for 25 min followed by
reperfusion for 30 min produced marked cardiac mechanical dysfunction in both
stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar
Kyoto rats (WKY). Exogenous treatment with S-nitroso-N-acetyl-dl-penicillamine
(SNAP), a NO donor, had beneficial effects on the cardiac dysfunction induced by
ischaemia-reperfusion (I/R) in the WKY heart, but the cardioprotective effect of
SNAP was eliminated by guanylyl cyclase inhibitor. Cardiac cGMP levels were
increased by SNAP or ischaemia in WKY. In contrast, in SHRSP hearts, SNAP could
not alleviate the cardiac dysfunction caused by I/R. Pre-ischaemia, the cardiac
cGMP level was significantly higher in SHRSP than in WKY; however, no significant
difference was found after SNAP and ischaemia. The myocardial Ca(2+)-dependent NO
synthase (NOS) activity increased at the end of ischaemia in WKY. Conversely, the
Ca(2+)-independent NOS activity and protein levels were upregulated by I/R in the
SHRSP myocardium. In the SHRSP hearts, non-selective NOS and selective Ca(2+)
independent NOS inhibitors or antioxidant treatment alleviated cardiac
dysfunction caused by I/R. Moreover, mRNA expression and Western blotting
analysis of cGMP-dependent protein kinase type I showed more deterioration of
SHRSP hearts compared with WKY. These results suggest that: (1) the NO-dependent
cardioprotective effect is depressed; and (2) overproduction of NO derived from
Ca(2+)-independent NOS contributes to postischaemic heart injury in the
hypertrophied heart of hypertensive status.
PMID- 17030560
TI - Exercise induces interleukin-8 receptor (CXCR2) expression in human skeletal
muscle.
AB - Exercise induces a marked increase in interleukin-8 (IL-8) mRNA and protein
expression within skeletal muscle fibres. Interleukin-8 belongs to a subfamily of
CXC chemokines containing a Glu-Leu-Arg (ELR) motif. CXC chemokines with ELR
motifs are potent angiogenic factors in vivo, and IL-8 has been shown to act as
an angiogenic factor in human microvascular endothelial cells by binding to the
CXC receptor 2 (CXCR2). In the present study, we examined the expression of the
interleukin-8 receptor CXCR2 in human skeletal muscle biopsies after concentric
exercise. Healthy volunteers were randomized to either 3 h of cycle ergometer
exercise at 60% of maximum oxygen uptake (n = 8) or rest (n = 7). Muscle biopsy
samples were obtained from the vastus lateralis before exercise (0 h),
immediately after exercise (3 h), and at 4.5, 6, 9 and 24 h. Skeletal muscle
CXCR2 mRNA increased significantly in response to exercise (3 and 4.5 h) when
compared with pre-exercise samples. Expression of the CXCR2 protein was low in
skeletal muscle biopsies before exercise and at the end of the exercise period (3
h). However, at 4.5-9 h, an increase in CXCR2 protein was seen in the vascular
endothelium, and also slightly within the muscle fibres, as determined by
immunohistochemistry. The present study demonstrates that concentric exercise
induces CXCR2 mRNA and protein expression in the vascular endothelial cells of
the muscle fibres. These findings suggest that muscle-derived IL-8 may act
locally to stimulate angiogenesis through CXCR2 receptor signalling.
PMID- 17030561
TI - First-in-first-out item replacement in a model of short-term memory based on
persistent spiking.
AB - Persistent neuronal firing has been modeled in relation to observed brain
rhythms, especially to theta oscillations recorded in behaving animals. Models of
short-term memory that are based on such persistent firing properties of specific
neurons can meet the requirements of spike-timing-dependent potentiation of
synaptic strengths during the encoding of a temporal sequence of spike patterns.
We show that such a spiking buffer can be simulated with integrate-and-fire
neurons that include a leak current even when different numbers of spikes
represent successive items. We propose a mechanism that successfully replaces
items in the buffer in first-in-first-out (FIFO) order when the distribution of
spike density in a theta cycle is asymmetric, as found in experimental data. We
predict effects on the function and capacity of the buffer model caused by
changes in modeled theta cycle duration, the timing of input to the buffer, the
strength of recurrent inhibition, and the strength and timing of after
hyperpolarization and after-depolarization (ADP). Shifts of input timing or
changes in ADP parameters can enable the reverse-order buffering of items, with
FIFO replacement in a full buffer. As noise increases, the simulated buffer
provides robust output that may underlie episodic encoding.
PMID- 17030562
TI - Biocompatibility of solid-dosage forms of anti-human immunodeficiency virus type
1 microbicides with the human cervicovaginal mucosa modeled ex vivo.
AB - Topical anti-human immunodeficiency virus (HIV) microbicides are being sought to
reduce the spread of HIV type 1 (HIV-1) during sexual intercourse. The success of
this strategy depends upon the selection of formulations compatible with the
natural vaginal mucosal barrier. This study applied ex vivo-modeled human
cervicovaginal epithelium to evaluate experimental solid-dosage forms of the anti
HIV-1 microbicide cellulose acetate 1,2-benzenedicarboxylate (CAP) and over-the
counter (OTC) vaginal products for their impact on inflammatory mediators
regarded as potential HIV-1-enhancing risk factors. We assessed product-induced
imbalances between interleukin-1alpha (IL-1alpha) and IL-1beta and the natural IL
1 receptor antagonist (IL-1RA) and changes in levels of IL-6, tumor necrosis
factor alpha, IL-8, gamma interferon inducible protein 10 (IP-10), and macrophage
inflammatory protein 3alpha (MIP-3alpha), known to recruit and activate
monocytes, dendritic cells, and T cells to the inflamed mucosa. CAP film and gel
formulation, similarly to the hydroxyethylcellulose universal vaginal placebo gel
and the OTC K-Y moisturizing gel, were nontoxic and caused no significant changes
in any inflammatory biomarker. In contrast, OTC vaginal cleansing and
contraceptive films containing octoxynol-9 or nonoxynol-9 (N-9) demonstrated
similar levels of toxicity but distinct immunoinflammatory profiles. IL-1alpha,
IL-1beta, IL-8, and IP-10 were increased after treatment with both OTC vaginal
cleansing and contraceptive films; however, MIP-3alpha was significantly elevated
by the N-9-based film only (P < 0.01). Although both films increased
extracellular IL-1RA, the cleansing film only significantly elevated the IL
1RA/IL-1 ratio (P < 0.001). The N-9-based film decreased intracellular IL-1RA (P
< 0.05), which has anti-inflammatory intracrine functions. This study identifies
immunoinflammatory biomarkers that can discriminate between formulations better
than toxicity assays and should be clinically validated in relevance to the risk
of HIV-1 acquisition.
PMID- 17030563
TI - Novel alpha interferon (IFN-alpha) variant with improved inhibitory activity
against hepatitis C virus genotype 1 replication compared to IFN-alpha2b therapy
in a subgenomic replicon system.
AB - Hepatitis C virus (HCV) treatment is based on the association of pegylated alpha
interferon (IFN-alpha) and ribavirin. To improve the level of sustained
virological response to treatment, especially in patients infected with HCV
genotype 1, new IFNs with improved efficacy and toxicity profiles may be
developed. In this report, we show that, in the BM4-5 cell line harboring an HCV
subgenomic replicon, a novel and naturally occurring human IFN-alpha17 variant,
GEA007.1, which was discovered by using an original population genetics-based
drug discovery approach, inhibits HCV genotype 1 RNA replication more efficiently
than does IFN-alpha2b. Moreover, we show that complete viral clearance is
obtained in BM4-5 cells after long-term treatment with GEA007.1, while HCV
subgenomic RNA is still detected in cells treated with other IFN-alpha variants
or with standard IFN-alpha2b. Eventually, we demonstrate that the better
inhibitory activity of GEA007.1 compared to that of standard IFN-alpha is likely
to be due to stronger and faster activation of the JAK-STAT signaling pathway and
to broader expression of IFN-alpha-responsive genes in cells. Our results
demonstrate a superior inhibitory activity of GEA007.1 over that of IFN-alpha2b
in the HCV replicon system. Clinical trials are required to determine whether
GEA007.1 could be a potent "next generation" IFN for the treatment of HCV
infection, especially in nonresponders or relapsing patients infected with HCV
genotype 1 who currently represent a clinical unmet need.
PMID- 17030564
TI - Modification of enrofloxacin treatment regimens for poultry experimentally
infected with Salmonella enterica serovar Typhimurium DT104 to minimize selection
of resistance.
AB - We hypothesized that higher doses of fluoroquinolones for a shorter duration
could maintain efficacy (as measured by reduction in bacterial count) while
reducing selection in chickens of bacteria with reduced susceptibility. Chicks
were infected with Salmonella enterica serovar Typhimurium DT104 and treated 1
week later with enrofloxacin at the recommended dose for 5 days (water dose
adjusted to give 10 mg/kg of body weight of birds or equivalence, i.e., water at
50 ppm) or at 2.5 or 5 times the recommended dose for 2 days or 1 day,
respectively. The dose was delivered continuously (ppm) or pulsed in the water
(mg/kg) or by gavage (mg/kg). In vitro in sera, increasing concentrations of 0.5
to 8 microg/ml enrofloxacin correlated with increased activity. In vivo, the
efficacy of the 1-day treatment was significantly less than that of the 2- and 5
day treatments. The 2-day treatments showed efficacy similar to that of the 5-day
treatment in all but one repeat treatment group and significantly (P < 0.01)
reduced the Salmonella counts. Dosing at 2.5x the recommended dose and pulsed
dosing both increased the peak antibiotic concentrations in cecal contents,
liver, lung, and sera as determined by high-pressure liquid chromatography. There
was limited evidence that shorter treatment regimens (in particular the 1-day
regimen) selected for fewer strains with reduced susceptibility. In conclusion,
the 2-day treatment would overall require a shorter withholding time than the 5
day treatment and, in view of the increased peak antibiotic concentrations, may
give rise to improved efficacy, in particular for treating respiratory and
systemic infections. However, it would be necessary to validate the 2-day regimen
in a field situation and in particular against respiratory and systemic
infections to validate or refute this hypothesis.
PMID- 17030565
TI - Quantitative analysis of tpr gene expression in Treponema pallidum isolates:
Differences among isolates and correlation with T-cell responsiveness in
experimental syphilis.
AB - Transcriptional analysis of the tpr genes in Treponema pallidum subsp. pallidum
(referred to here as simply T. pallidum) has been limited to date, and yet the
expression of members of this gene family is likely relevant to the pathogenesis
of syphilis. Recently, immunological studies and semiquantitative mRNA analysis
led to the hypothesis of the modulation of tpr gene transcription during
infection and suggested that various strains of T. pallidum might differentially
express these genes. In this study we developed a real-time amplification assay
to quantify the tpr mRNAs with respect to the 47-kDa lipoprotein message and to
compare transcript levels among four different strains of T. pallidum. In
addition, we analyzed the lymphocyte responsiveness pattern toward the Tpr
antigens in late experimental syphilis to identify tpr genes that had been
expressed during the course of infection. The T-cell response has been implicated
in clearance of treponemes from early lesions, and some of the Tprs were
identified as strong targets of the cellular immune response. We show that
message for many of the tpr genes can be detected in treponemes harvested at the
peak of early infection. Interestingly, tprK seems to be preferentially expressed
in almost every strain, and it is uniformly the target of the strongest cellular
immune response. These studies demonstrate the differential expression of certain
tpr genes among strains of T. pallidum, and further studies are needed to explore
the relationship between tpr gene expression and the clinical course of syphilis
in infected individuals.
PMID- 17030566
TI - Identification of genes involved in the expression of atypical
lipooligosaccharide structures from a second class of Haemophilus ducreyi.
AB - Haemophilus ducreyi is a gram-negative bacterium that is the causative agent of
chancroid. Strain 35000HP has been well characterized and is representative of
the majority of H. ducreyi strains. Strain 35000HP produces a lipooligosaccharide
(LOS) that contains D-glycero-D-manno-heptose in the main oligosaccharide chain
extension; the lbgB gene has been shown to encode the DD-heptosyltransferase. The
lbgB gene is found in a gene cluster together with the lbgA gene, which encodes
for the galactosyltransferase I. These two genes are flanked by two housekeeping
genes, rpmE and xthA, encoding the ribosomal protein L31 and the exonuclease III,
respectively. Recently, a second group of H. ducreyi strains have been
identified. Strain 33921, a representative of the class II strains, produces an
LOS that lacks DD-heptose in the oligosaccharide portion of its LOS. To better
understand the biosynthesis of the DD-heptose-deficient 33921 LOS, we cloned and
sequenced the corresponding lbgAB genomic region from strain 33921. Similar to
strain 35000HP, the 33921 genome contains xthA and rpmE. However, between these
two genes we identified genes encoding two putative glycosyltransferases that
were not highly homologous to the 35000HP lbgAB genes. In this study, we
demonstrate that the product of one of these genes encodes a
galactosyltransferase. In addition, dot blot hybridization determined that 3 of
35 strains tested had the atypical transferases present, as did 4 strains
characterized as class II strains by other criterion. These data indicate that
the lbgAB genes can serve as one indicator of the classification of H. ducreyi
strains.
PMID- 17030567
TI - Signature-tagged transposon mutagenesis identifies novel Mycobacterium
tuberculosis genes involved in the parasitism of human macrophages.
AB - Using signature-tagged transposon mutagenesis, we isolated 23 Mycobacterium
tuberculosis mutants, corresponding to 21 genes or genetic regions, attenuated in
their ability to parasitize human macrophages. Mutants disrupted in the ABC
transporter-encoding genes Rv0986 and Rv0987 were further characterized as being
impaired in their ability to bind to host cells.
PMID- 17030568
TI - A Mycobacterium marinum mel2 mutant is defective for growth in macrophages that
produce reactive oxygen and reactive nitrogen species.
AB - Macrophages produce reactive oxygen species (ROS) and reactive nitrogen species
(RNS) in response to bacterial infections. Mycobacteria are relatively resistant
to ROS, but RNS inhibit growth of, and possibly even kill, mycobacteria in
activated macrophages. We recently constructed a Mycobacterium marinum mel2 locus
mutant, which is known to affect macrophage infection. We found previously that
the mel2 locus confers resistance to ROS and RNS in laboratory medium, suggesting
that this locus might play a similar role during growth in macrophages. Since
J774A.1 murine macrophages produce high levels of ROS and RNS upon activation
with gamma interferon (IFN-gamma), we examined the effects of IFN-gamma on ROS
and RNS production by these cells as well as the effects on growth of M. marinum
in these cells. We found that an M. marinum mutant with mutation of the first
gene in the mel2 locus, melF, is defective for growth in IFN-gamma-plus
lipopolysaccharide-treated J774A.1 cells and that this defect is abrogated by the
presence of either inhibitors of nitric oxide synthase or ROS scavengers.
Furthermore, the M. marinum melF mutant displays a defect at late stages in the
mouse footpad model of infection. These phenotypic characteristics could be
complemented fully by the entire mel2 locus but only partially by the presence of
melF alone, supporting data suggesting that this insertion mutation has polar
effects on downstream genes in the mel2 locus. These observations demonstrate
that the M. marinum mel2 locus plays a role in resistance to ROS and RNS produced
by activated macrophages.
PMID- 17030569
TI - V beta1+ J beta1.1+/V alpha2+ J alpha49+ CD4+ T cells mediate resistance against
infection with Blastomyces dermatitidis.
AB - Immunization with a cell wall/membrane (CW/M) and yeast cytosol extract (YCE)
crude antigen from Blastomyces dermatitidis confers T-cell-mediated resistance
against lethal experimental infection in mice. We isolated and characterized T
cells that recognize components of these protective antigens and mediate
protection. CD4+ T-cell clones elicited with CW/M antigen adoptively transferred
protective immunity when they expressed a V alpha2+ J alpha49+/V beta1+ J
beta1.1+ heterodimeric T-cell receptor (TCR) and produced high levels of gamma
interferon (IFN-gamma). In contrast, V beta8.1/8.2+ CD4+ T-cell clones that were
reactive against CW/M and YCE antigens and produced little or no IFN-gamma either
failed to mediate protection or exacerbated the infection depending on the level
of interleukin-5 expression. Thus, the outgrowth of protective T-cell clones
against immunodominant antigens of B. dermatitidis is biased by a combination of
the TCR repertoire and Th1 cytokine production.
PMID- 17030570
TI - Biological Trojan horse: Antigen 43 provides specific bacterial uptake and
survival in human neutrophils.
AB - Escherichia coli is a versatile pathogen causing millions of infections in humans
every year. This bacterium can form multicellular aggregates when it expresses a
self-associating protein, antigen 43 (Ag43), on its surface. We have discovered
that Ag43-expressing E. coli cells are efficiently taken up by human defense
cells, polymorphonuclear neutrophils (PMNs), in an opsonin-independent manner.
Surprisingly, the phagocytosed bacteria were not immediately killed but resided
as tight aggregates within the PMNs. Our observations indicate that Ag43-mediated
uptake and survival in PMNs constitute a mechanism to subvert one of the primary
defense mechanisms of the human body.
PMID- 17030571
TI - Role of the wbt locus of Francisella tularensis in lipopolysaccharide O-antigen
biogenesis and pathogenicity.
AB - Francisella tularensis is a highly infectious bacterial pathogen, responsible for
the zoonotic disease tularemia. We screened a bank of transposon insertion
mutants of F. tularensis subsp. holarctica LVS for colony morphology alterations
and selected a mutant with a transposon insertion in wbtA, the first gene of the
predicted lipopolysaccharide O-antigen gene cluster. Inactivation of wbtA led to
the complete loss of O antigen, conferred serum sensitivity, impaired
intracellular replication, and severely attenuated virulence in the mouse model.
Notably, this mutant afforded protection against a challenge against virulent
LVS.
PMID- 17030572
TI - The SecA2 secretion factor of Mycobacterium tuberculosis promotes growth in
macrophages and inhibits the host immune response.
AB - The SecA protein is present in all bacteria, and it is a central component of the
general Sec-dependent protein export pathway. An unusual property of
Mycobacterium tuberculosis is the presence of two SecA proteins: SecA1, the
essential "housekeeping" SecA, and SecA2, the accessory secretion factor. Here,
we report that a DeltasecA2 mutant of M. tuberculosis was defective for growth in
the early stages of low-dose aerosol infection of C57BL/6 mice, a time during
which the bacillus is primarily replicating in macrophages. Consistent with this
in vivo phenotype, we found that the DeltasecA2 mutant was defective for growth
in macrophages from C57BL/6 mice. The DeltasecA2 mutant was also attenuated for
growth in macrophages from phox(-/-) mice and from NOS2(-/-) mice. These mice are
defective in the reactive oxygen intermediate (ROI)-generating phagocyte oxidase
and the reactive nitrogen intermediate (RNI)-generating inducible nitric oxide
synthase, respectively. This indicated a role for SecA2 in the intracellular
growth of M. tuberculosis that is independent of protecting against these ROIs or
RNIs. Macrophages infected with the DeltasecA2 mutant produced higher levels of
tumor necrosis factor alpha, interleukin-6, RNI, and gamma interferon-induced
major histocompatibility complex class II. This demonstrated a function for M.
tuberculosis SecA2 in suppressing macrophage immune responses, which could
explain the role of SecA2 in intracellular growth. Our results provide another
example of a relationship between M. tuberculosis virulence and inhibition of the
host immune response.
PMID- 17030573
TI - Long-term staphylococcal enterotoxin C1 exposure induces soluble factor-mediated
immunosuppression by bovine CD4+ and CD8+ T cells.
AB - Regulatory T cells (T(regs)) help control the development and maintenance of
protective immunity and can lead to aberrant immune responses to some pathogens.
Several lines of evidence suggest that T(regs) are induced by exposure to
superantigens (SAgs) in vitro or in vivo. In this study, bovine peripheral blood
mononuclear cells (PBMC) were exposed in vitro to a relatively low dose (5 ng/ml)
of staphylococcal enterotoxin C1 (SEC1) for up to 10 days. Upon stimulation, CD4+
and CD8+ T cells initially proliferated at similar rates. Subsequently, from days
6 through 10, most CD4+ and CD8+ T cells proliferated regardless of Vbeta
specificity, but the proliferation of CD8+ T cells occurred more vigorously. The
transcription of CD25 and CD152 genes increased, whereas that of interleukin-2
(IL-2) decreased. gammadelta T cells appeared to be unresponsive. An increase in
the transcription of IL-10 and transforming growth factor beta (TGF-beta) genes
in SEC1-stimulated cultures was attributed to the CD4+ CD25+ T-cell
subpopulation. The expression of Foxp3 mRNA also increased and was accompanied by
the upregulation of CD152 and the downregulation of IL-2 transcription,
suggesting that cells in this subpopulation are T(regs). Functionally, SEC1
stimulated CD4+ T cells suppressed the proliferation of naive PBMC in response to
heat-killed-fixed Staphylococcus aureus. The suppression was partially mediated
by IL-10 and TGF-beta, another characteristic of certain types of T(regs.) The
CD8+ T-cell population also suppressed naive PBMC through another mechanism not
mediated by IL-10 or TGF-beta. These results provide further insight into the
potential mechanisms by which SAgs could contribute to evasion of the immune
response, affecting the outcome of infection or colonization.
PMID- 17030574
TI - Up-regulation of gamma interferon receptor expression due to Chlamydia-toll-like
receptor interaction does not enhance signal transducer and activator of
transcription 1 signaling.
AB - Gamma interferon (IFN-gamma)-induced indoleamine dioxygenase (IDO), which
inhibits chlamydial replication by reducing the availability of tryptophan, is up
regulated by interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF
alpha). The mechanisms by which this occurs include an increase in the synthesis
of interferon regulatory factor-1 as well as a nuclear factor-kappaB (NF-kappaB)
dependent increase in the expression of IFN-gamma receptors (IFN-gammaR).
Although Chlamydia is susceptible to IDO, it up-regulates IFN-gammaR expression
to a greater degree than either IL-1beta or TNF-alpha, perhaps through
interaction with Toll-like receptors (TLR). The purpose of this study was to
determine the mechanism by which Chlamydia psittaci up-regulates IFN-gammaR
expression and evaluate this effect on IDO induction. Infection of HEK 293 cells
with C. psittaci increased IFN-gammaR expression only in cells expressing either
TLR2 or TLR4 and the adaptor protein MD-2. In addition, up-regulation of IFN
gammaR expression in Chlamydia-infected HeLa cells could be blocked either by
neutralizing TLRs with anti-TLR2 and/or anti-TLR4 or by inhibiting NF-kappaB
transactivation with a proteasome inhibitor. Although the newly expressed IFN
gammaR in Chlamydia-infected cells were capable of binding IFN-gamma, they did
not enhance IFN-gamma-induced IDO activity in a manner similar to those observed
for IL-1beta and TNF-alpha. Instead, IDO activation in Chlamydia-infected cells
was no different than that induced in uninfected cells, despite the increase in
IFN-gammaR expression. Furthermore, the amount of IFN-gamma-induced signal
transducer and activator of transcription 1 (STAT-1) activation in infected cells
paralleled that observed in uninfected cells, suggesting that STAT-1 activation
by these newly expressed receptors was impaired.
PMID- 17030575
TI - Role of neutrophils in invasive aspergillosis.
PMID- 17030576
TI - The 13C4 monoclonal antibody that neutralizes Shiga toxin Type 1 (Stx1)
recognizes three regions on the Stx1 B subunit and prevents Stx1 from binding to
its eukaryotic receptor globotriaosylceramide.
AB - The 13C4 monoclonal antibody (MAb) recognizes the B subunit of Stx1 (StxB1) and
neutralizes the cytotoxic and lethal activities of Stx1. However, this MAb does
not bind to the B polypeptide of Stx2, despite the 73% amino acid sequence
similarity between StxB1 and StxB2. When we compared the amino acid sequences of
StxB1 and StxB2, we noted three regions of dissimilarity (amino acids 1 to 6, 25
to 32, and 54 to 61) located near each other on the crystal structure of StxB1.
To identify the 13C4 epitope, we generated seven Stx1/Stx2 B chimeric
polypeptides that contained one, two, or three of the dissimilar StxB1 regions.
The 13C4 MAb reacted strongly with StxB1 and the triple-chimeric B subunit but
not with the other chimeras. Mice immunized with the triple-chimeric B subunit
survived a lethal challenge with Stx1 but not Stx2, substantiating the identified
regions as the 13C4 MAb epitope and suggesting that the incorporation of this
epitope into StxB2 altered sites necessary for anti-Stx2-neutralizing Ab
production. Next, single amino acid substitutions were made in StxB1 to mimic
Stx1d, a variant not recognized by the 13C4 MAb. The 13C4 MAb reacted strongly to
StxB1 with the T1A or G25A mutations but not with the N55T change. Finally, we
found that the 13C4 MAb blocked the binding of Stx1 to its receptor,
globotriaosyl ceramide. Taken together, these results indicate that the 13C4 MAb
prevents the interaction of Stx1 with its receptor by binding three nonlinear
regions of the molecule that span receptor recognition sites on StxB1, one of
which includes the essential residue 55N.
PMID- 17030577
TI - Dual Roles of Helicobacter pylori NapA in inducing and combating oxidative
stress.
AB - Neutrophil-activating protein (NapA) has been well documented to play roles in
human neutrophil recruitment and in stimulating host cell production of reactive
oxygen intermediates (ROI). A separate role for NapA in combating oxidative
stress within H. pylori was implied by studies of various H. pylori mutant
strains. Here, physiological analysis of a napA strain was the approach used to
assess the iron-sequestering and stress resistance roles of NapA, its role in
preventing oxidative DNA damage, and its importance to mouse colonization. The
napA strain was more sensitive to oxidative stress reagents and to oxygen, and it
contained fourfold more intracellular free iron and more damaged DNA than the
parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not,
presumably linking iron levels sensed by NapA to DNA damage protection. Despite
its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed
normal (like that of the wild type) mouse colonization efficiency in the
conventional in vivo assay. By use of a modified mouse inoculation protocol
whereby nonviable H. pylori is first inoculated into mice, followed by (live)
bacterial strain administration, an in vivo role for NapA in colonization
efficiency could be demonstrated. NapA is the critical component responsible for
inducing host-mediated ROI production, thus inhibiting colonization by the napA
strain. An animal colonization experiment with a mixed-strain infection protocol
further demonstrated that the napA strain has significantly decreased ability to
survive when competing with the wild type. H. pylori NapA has unique and separate
roles in gastric pathogenesis.
PMID- 17030578
TI - Induction of the antimicrobial peptide CRAMP in the blood-brain barrier and
meninges after meningococcal infection.
AB - Antimicrobial peptides are present in most living species and constitute
important effector molecules of innate immunity. Recently, we and others have
detected antimicrobial peptides in the brain. This is an organ that is rarely
infected, which has mainly been ascribed to the protective functions of the blood
brain barrier (BBB) and meninges. Since the bactericidal properties of the BBB
and meninges are not known, we hypothesized that antimicrobial peptides could
play a role in these barriers. We addressed this hypothesis by infecting mice
with the neuropathogenic bacterium Neisseria meningitidis. Brains were analyzed
for expression of the antimicrobial peptide CRAMP by immunohistochemistry in
combination with confocal microscopy. After infection, we observed induction of
CRAMP in endothelial cells of the BBB and in cells of the meninges. To explore
the functional role of CRAMP in meningococcal disease, we infected mice deficient
of the CRAMP gene. Even though CRAMP did not appear to protect the brain from
invasion of meningococci, CRAMP knockout mice were more susceptible to
meningococcal infection than wild-type mice and exhibited increased meningococcal
growth in blood, liver, and spleen. Moreover, we could demonstrate that
carbonate, a compound that accumulates in the circulation during metabolic
acidosis, makes meningococci more susceptible to CRAMP.
PMID- 17030579
TI - Helicobacter pylori HP1512 is a nickel-responsive NikR-regulated outer membrane
protein.
AB - Helicobacter pylori is dependent upon the production of the highly abundant and
active metalloenzyme urease for colonization of the human stomach. Thus, H.
pylori has an absolute requirement for the transition metal nickel, a required
cofactor for urease. To investigate the contribution of genes that are factors in
this process, microarray analysis comparing the transcriptome of wild-type H.
pylori 26695 cultured in brucella broth containing fetal calf serum (BBF) alone
or supplemented with 100 microM NiCl(2) suggested that HP1512 is repressed in the
presence of 100 microM supplemental nickel. When measured by comparative real
time quantitative PCR (qPCR), HP1512 transcription was reduced 43-fold relative
to the value for the wild type when cultured in BBF supplemented with 10 microM
NiCl(2). When grown in unsupplemented BBF, urease activity of an HP1512::cat
mutant was significantly reduced compared to the wild type, 4.9 +/- 0.5
micromol/min/mg of protein (n = 7) and 17.1 +/- 4.9 micromol/min/mg of protein (n
= 13), respectively (P < 0.0001). In silico analysis of the HP1511-HP1512 (HP1511
1512) intergenic region identified a putative NikR operator upstream of HP1512.
Gel shift analysis with purified recombinant NikR verified nickel-dependent
binding of H. pylori NikR to the HP1511-1512 intergenic region. Furthermore,
comparative real-time qPCR of four nickel-related genes suggests that mutation of
HP1512 results in reduced intracellular nickel concentration relative to wild
type H. pylori 26695. Taken together, these data suggest that HP1512 encodes a
NikR-nickel-regulated outer membrane protein.
PMID- 17030580
TI - Microneedle-based intradermal delivery of the anthrax recombinant protective
antigen vaccine.
AB - The recombinant protective antigen (rPA) of Bacillus anthracis is a promising
anthrax vaccine. We compared serum immunoglobulin G levels and toxin-neutralizing
antibody titers in rabbits following delivery of various doses of vaccine by
microneedle-based intradermal (i.d.) delivery or intramuscular (i.m.) injection
using conventional needles. Intradermal delivery required less antigen to induce
levels of antibody similar to those produced via i.m. injection during the first
2 weeks following primary and booster inoculation. This dose-sparing effect was
less evident at the later stages of the immune response. Rabbits immunized i.d.
with 10 mug of rPA displayed 100% protection from aerosol spore challenge, while
i.m. injection of the same dose provided slightly lower protection (71%). Groups
immunized with lower antigen doses were partially protected (13 to 29%)
regardless of the mode of administration. Overall, our results suggest rPA
formulated with aluminum adjuvant and administered to the skin by a microneedle
based device is as efficacious as i.m. vaccination.
PMID- 17030581
TI - Dual role of MyD88 in rapid clearance of relapsing fever Borrelia spp.
AB - Relapsing fever Borrelia spp. undergo antigenic variation, achieve high levels in
blood, and require rapid production of immunoglobulin M (IgM) for clearance.
MyD88-deficient mice display defective clearance of many pathogens; however, the
IgM response to persistent infection is essentially normal. Therefore, MyD88(-/-)
mice provided a unique opportunity to study the effect of nonantibody, innate
host defenses to relapsing fever Borrelia. Infected MyD88(-/-) mice harbored
extremely high levels of B. hermsii in the blood compared to wild-type
littermates. In the comparison of MyD88(-/-) mice and B- and T-cell-deficient
scid mice, two features stood out: (i) bacterial numbers in blood were at least
10-fold greater in MyD88(-/-) mice than scid mice, even though the production of
IgM still occurred in MyD88(-/-) mice; and (ii) many of the MyD88(-/-) mice were
able to exert partial clearance, although with delayed kinetics relative to wild
type mice, a feature not seen in scid mice. Further analysis revealed a delay in
the IgM response to lipoproteins expressed by the original inoculum; however, by
6 days of infection antibodies were produced in MyD88(-/-) mice that could clear
spirochetemia in scid mice. While these results indicated that the production of
IgM was delayed in MyD88(-/-) mice, they also point to a second, antibody
independent role for MyD88 signaling in host defense to relapsing fever Borrelia.
This second defect was apparent only when antibody levels were limiting.
PMID- 17030582
TI - GliZ, a transcriptional regulator of gliotoxin biosynthesis, contributes to
Aspergillus fumigatus virulence.
AB - Gliotoxin is a nonribosomal peptide produced by Aspergillus fumigatus. This
compound has been proposed as an A. fumigatus virulence factor due to its
cytotoxic, genotoxic, and apoptotic properties. Recent identification of the
gliotoxin gene cluster identified several genes (gli genes) likely involved in
gliotoxin production, including gliZ, encoding a putative Zn(2)Cys(6) binuclear
transcription factor. Replacement of gliZ with a marker gene (DeltagliZ) resulted
in no detectable gliotoxin production and loss of gene expression of other gli
cluster genes. Placement of multiple copies of gliZ in the genome increased
gliotoxin production. Using endpoint survival data, the DeltagliZ and a multiple
copy gliZ strain were not statistically different from the wild type in a murine
pulmonary model; however, both the wild-type and the multiple-copy gliZ strain
were more virulent than DeltalaeA (a mutant reduced in production of gliotoxin
and other toxins). A flow-cytometric analysis of polymorphonuclear leukocytes
(PMNs) exposed to supernatants from wild-type, DeltagliZ, complemented DeltagliZ,
and DeltalaeA strains supported a role for gliotoxin in apoptotic but not
necrotic PMN cell death. This may indicate that several secondary metabolites are
involved in A. fumigatus virulence.
PMID- 17030583
TI - Clustering of Helicobacter pylori VacA in lipid rafts, mediated by its receptor,
receptor-like protein tyrosine phosphatase beta, is required for intoxication in
AZ-521 Cells.
AB - Helicobacter pylori vacuolating cytotoxin, VacA, induces multiple effects on
epithelial cells through different cellular events: one involves pore formation,
leading to vacuolation, mitochondrial damage, and apoptosis, and the second
involves cell signaling, resulting in stimulation of proinflammatory responses
and cell detachment. Our recent data demonstrated that VacA uses receptor-like
protein tyrosine phosphatase beta (RPTPbeta) as a receptor, of which five
residues (QTTQP) at positions 747 to 751 are involved in binding. In AZ-521
cells, which mainly express RPTPbeta, VacA, after binding to RPTPbeta in non
lipid raft microdomains on the cell surface, is localized with RPTPbeta in lipid
rafts in a temperature- and VacA concentration-dependent process. Methyl-beta
cyclodextrin (MCD) did not block binding to RPTPbeta but inhibited translocation
of VacA with RPTPbeta to lipid rafts and all subsequent events. On the other
hand, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), which disrupts anion
channels, did not inhibit translocation of VacA to lipid rafts or VacA-induced
activation of p38 mitogen-activated protein (MAP) kinase, but inhibited VacA
internalization followed by vacuolation. Thus, p38 MAP kinase activation did not
appear to be required for internalization. In contrast, phosphatidylinositol
specific phospholipase C (PI-PLC) inhibited translocation, as well as p38 MAP
kinase/ATF-2 activation, internalization, and VacA-induced vacuolation. Neither
NPPB nor PI-PLC affected VacA binding to cells and to its receptor, RPTPbeta.
Thus, receptor-dependent translocation of VacA to lipid rafts is critical for
signaling pathways leading to p38 MAP kinase/ATF-2 activation and vacuolation.
PMID- 17030584
TI - A linear peptide containing minimal T- and B-cell epitopes of Plasmodium
falciparum circumsporozoite protein elicits protection against transgenic
sporozoite challenge.
AB - An effective malaria vaccine is needed to address the public health tragedy
resulting from the high levels of morbidity and mortality caused by Plasmodium
parasites. The first protective immune mechanism identified in the irradiated
sporozoite vaccine, the "gold standard" for malaria preerythrocytic vaccines, was
sporozoite-neutralizing antibody specific for the repeat region of the surface
circumsporozoite (CS) protein. Previous phase I studies demonstrated that a
branched peptide containing minimal T- and B-cell epitopes of Plasmodium
falciparum CS protein elicited antirepeat antibody and CD4(+)-T-cell responses
comparable to those observed in volunteers immunized with irradiated P.
falciparum sporozoites. The current study compares the immunogenicity of linear
versus tetrabranched peptides containing the same minimal T- and B-cell epitopes,
T1BT*, comprised of a CS-derived universal Th epitope (T*) synthesized in tandem
with the T1 and B repeats of P. falciparum CS protein. A simple 48-mer linear
synthetic peptide was found to elicit antisporozoite antibody and gamma
interferon-secreting T-cell responses comparable to the more complex
tetrabranched peptides in inbred strains of mice. The linear peptide was also
immunogenic in outbred nonhuman primates (Aotus nancymaae), eliciting antibody
titers equivalent to those induced by tetrabranched peptides. Importantly, the 48
mer linear peptide administered in adjuvants suitable for human use elicited
antibody-mediated protection against challenge with rodent malaria transgenic
sporozoites expressing P. falciparum CS repeats. These findings support further
evaluation of linear peptides as economical, safe, and readily produced malaria
vaccines for the one-third of the world's population at risk of malaria
infection.
PMID- 17030585
TI - Surfactant protein D increases fusion of Mycobacterium tuberculosis-containing
phagosomes with lysosomes in human macrophages.
AB - Lung surfactant protein D (SP-D) binds to Mycobacterium tuberculosis surface
lipoarabinomannan and results in bacterial agglutination, reduced uptake, and
inhibition of growth in human macrophages. Here we show that SP-D limits the
intracellular growth of bacilli in macrophages by increasing phagosome-lysosome
fusion but not by generating a respiratory burst.
PMID- 17030586
TI - Diffusion anisotropy of the cervical cord is strictly associated with disability
in amyotrophic lateral sclerosis.
AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
with severe cervical cord damage due to degeneration of the corticospinal tracts
and loss of lower motor neurones. Diffusion tensor magnetic resonance imaging (DT
MRI) allows the measurement of quantities reflecting the size (such as mean
diffusivity) and orientation (such as fractional anisotropy) of water-filled
spaces in biological tissues. METHODS: Mean diffusivity and fractional anisotropy
histograms from the cervical cord of patients with ALS were obtained to: (1)
quantify the extent of tissue damage in this critical central nervous system
region; and (2) investigate the magnitude of the correlation of cervical cord DT
MRI metrics with patients' disability and tissue damage along the brain portion
of the corticospinal tracts. Cervical cord and brain DT MRI scans were obtained
from 28 patients with ALS and 20 age-matched and sex-matched controls. Cord mean
diffusivity and fractional anisotropy histograms were produced and the cord cross
sectional area was measured. Average mean diffusivity and fractional anisotropy
along the brain portion of the corticospinal tracts were also measured. RESULTS:
Compared with controls, patients with ALS had significantly lower mean fractional
anisotropy (p = 0.002) and cord cross-sectional area (p<0.001). Mean diffusivity
histogram-derived metrics did not differ between the two groups. A strong
correlation was found between mean cord fractional anisotropy and the ALS
Functional Rating Score (r = 0.74, p<0.001). Mean cord and brain fractional
anisotropy values correlated moderately (r = 0.37, p = 0.05). CONCLUSIONS:
Cervical cord DT MRI in patients with ALS allows the extent of cord damage to be
graded. The conventional and DT MRI changes found are compatible with the
presence of neuroaxonal loss and reactive gliosis, with a heterogeneous
distribution of the pathological process between the brain and the cord. The
correlation found between cord fractional anisotropy and disability suggests that
DT MRI may be a useful adjunctive tool to monitor the evolution of ALS.
PMID- 17030587
TI - Visual hallucinations and agitation in Alzheimer's disease due to memantine:
report of three cases.
PMID- 17030588
TI - Patterns of reoccurrence of segmental dystonia after discontinuation of deep
brain stimulation.
AB - The pattern of reoccurrence of symptoms after discontinuation of deep brain
stimulation (DBS) has not been systematically studied in dystonia. Eight patients
(mean age (SD) 53.8 (14.4) years) with segmental dystonia at a mean follow-up of
11.3 (4.2) months were studied after implantation of bilateral DBS electrodes in
the internal globus pallidus using a standard video protocol and clinical rating
scales, immediately and at 2 and 4 h after switching off DBS. Dystonic signs
returned sequentially, with a rapid worsening of phasic and a slower worsening of
tonic dystonic components. In all patients, phasic dystonic features appeared
within a few minutes, whereas the tonic elements of dystonia reoccurred with a
more variable delay. Differential clinical effects when withdrawing DBS might
reflect its influence on different pathophysiological mechanisms in dystonia.
PMID- 17030589
TI - Screening designs for drug development.
AB - We propose drug screening designs based on a Bayesian decision-theoretic
approach. The discussion is motivated by screening designs for phase II studies.
The proposed screening designs allow consideration of multiple treatments
simultaneously. In each period, new treatments can arise and currently considered
treatments can be dropped. Once a treatment is removed from the phase II
screening trial, a terminal decision is made about abandoning the treatment or
recommending it for a future confirmatory phase III study. The decision about
dropping treatments from the active set is a sequential stopping decision. We
propose a solution based on decision boundaries in the space of marginal
posterior moments for the unknown parameter of interest that relates to each
treatment. We present a Monte Carlo simulation algorithm to implement the
proposed approach. We provide an implementation of the proposed method as an easy
to use R library available for public domain download
(http://www.stat.rice.edu/~rusi/ or http://odin.mdacc.tmc.edu/~pm/).
PMID- 17030591
TI - Surgical manifestations of Paget's disease.
AB - Paget's disease is a chronic, nonmetabolic bone disorder characterized by
increased bone resorption, bone formation, and remodeling. This unbalanced
process may lead to osseous deformities, structural weakness, and altered joint
biomechanics, all of which can make surgical reconstruction difficult. Although
few patients with Paget's disease require surgical treatment, successful surgical
management of severe orthopaedic complications has improved the quality of life
for these patients. Surgical options include osteotomy to correct long-bone
deformity and arthroplasty to restore altered joint mechanics. Patients are at
increased risk for surgical complications, such as blood loss and heterotopic
bone formation. Issues relating to the surgical management of patients with
Paget's disease include appropriate preoperative diagnosis, technical challenges
of surgery, and strategies to improve the long-term outcome of surgical
intervention.
PMID- 17030592
TI - Metastatic disease of the spine.
AB - Metastatic spine disease accounts for 10% to 30% of new cancer diagnoses
annually. The most frequent presentation is axial pain. A thorough spinal
examination includes assessment of local tenderness, deformity, limitation of
motion, and signs of nerve root or cord compression. Plain radiographs are
obtained routinely; for a suspected or known malignancy, radionuclide studies are
essential. Magnetic resonance imaging is more specific than bone scans. Computed
tomography-guided biopsy is considered to be safe and accurate for evaluating
spinal lesions. Treatment is multidisciplinary, and virtually all treatment is
palliative. Management is guided by three key issues: neurologic compromise,
spinal instability, and individual patient factors. Site-directed radiation, with
or without chemotherapy, is the mainstay of treating painful lesions that are not
impinging on neural elements. New data documenting the benefit of surgical
decompression using improved techniques such as anterior approaches have
amplified the role of the spine surgeon in the care of these patients.
PMID- 17030593
TI - Rehabilitation of the rotator cuff: an evaluation-based approach.
AB - Rotator cuff disease of the shoulder, a common condition, is often
incapacitating. Whether nonsurgical or surgical, successful management of rotator
cuff disease is dependent on appropriate rehabilitation. Numerous rehabilitation
protocols for the management of rotator cuff disease are based primarily on
anecdotal clinical observation. The available literature on shoulder
rehabilitation, in conjunction with clinical observation that takes into
consideration the underlying tissue quality and structural integrity of the
rotator cuff, can be compiled into a set of rehabilitation guidelines. The four
phases of rehabilitation begin with maintaining and protecting the repair in the
immediate postoperative period, followed by progression from early passive range
of motion through return to preoperative levels of function.
PMID- 17030594
TI - Down syndrome in children: the role of the orthopaedic surgeon.
AB - Down syndrome, the result of trisomy of chromosome 21, is one of the most common
chromosomal abnormalities. Patients have a characteristic facial appearance,
variable levels of intelligence and self-care skills, and a variety of associated
medical conditions. Orthopaedic manifestations occur frequently; most are related
to hypotonia, joint hypermobility, and ligamentous laxity. Atlanto-occipital and
atlantoaxial hypermobility, as well as bony anomalies of the cervical spine, can
produce atlanto-occipital and cervical instability. Methods of screening for this
instability, particularly with regard to participation in sports, are a subject
of controversy. Scoliosis, hip instability, slipped capital femoral epiphysis,
patellar instability, and foot deformities are other musculoskeletal conditions
found in patients with Down syndrome that can be challenging for the orthopaedic
surgeon to treat.
PMID- 17030595
TI - Impaction bone grafting for revision hip arthroplasty: biology and clinical
applications.
AB - Impaction bone grafting techniques are useful when the orthopaedic surgeon is
faced with large cavitary acetabular defects or a large ectatic femoral
metaphysis or diaphysis. Impaction bone grafting of the acetabulum involves
packing of cavitary defects with compressed particulate graft, followed by
insertion of either a cemented or cementless acetabular component. Impaction
grafting of the femur involves retrograde filling of the femoral canal with
impacted particulate graft, creating a neomedullary canal into which a cemented
femoral stem can be placed. Use of the impaction allografting technique is
appealing, especially in young patients, because of its potential to restore bone
stock. The technically demanding nature of the procedure, the risk of
complications, and the unknown long-term fate of the impacted allograft highlight
the need for ongoing assessment of this technique for revision total hip
arthroplasties.
PMID- 17030597
TI - Characterization of immunodeficiency in a patient with growth hormone
insensitivity secondary to a novel STAT5b gene mutation.
AB - STAT5 proteins are components of the common growth hormone and interleukin 2
family of cytokines' signaling pathway. Mutations in the STAT5b gene, described
in 2 patients, lead to growth hormone insensitivity that resembles Laron
syndrome. Clinical immunodeficiency was also present, although immunologic
defects have not been well characterized thus far. Here we describe a 16-year-old
girl who suffered generalized eczema and recurrent infections of the skin and
respiratory tract since birth. She also suffered severe chronic lung disease and
multiple episodes of herpetic keratitis. Clinical features of congenital growth
hormone deficiency were observed, such as persistently low growth rate, severely
delayed bone age, and postnatal growth failure resulting from growth hormone
resistance. This combined phenotype of growth hormone insensitivity and
immunodeficiency was attributable to a homozygous C-->T transition that resulted
in a nonsense mutation at codon 152 in exon 5 of the STAT5b gene. This novel
mutation determined a complete absence of protein expression. The main
immunologic findings were moderate T-cell lymphopenia (1274/mm3), normal CD4/CD8
ratio, and very low numbers of natural killer (18/mm3) and gammadelta T (5/mm3)
cells. T cells presented a chronically hyperactivated phenotype. In vitro T-cell
proliferation and interleukin 2 signaling were impaired. CD4+ and CD25+
regulatory T cells were significantly diminished, and they probably contributed
to the signs of homeostatic mechanism deregulation found in this patient. This
new case, in accordance with 2 previously reported cases, definitely demonstrates
the significant role of the STAT5b protein in mediating growth hormone actions.
Furthermore, the main immunologic findings bring about an explanation for the
clinical immunodeficiency features and reveal for the first time the relevant
role of STAT5b as a key protein for T-cell functions in humans.
PMID- 17030598
TI - Exposure to medical test irradiation and acute leukemia among children with Down
syndrome: a report from the Children's Oncology Group.
AB - OBJECTIVE: The etiology of acute childhood leukemia is not well understood,
particularly among children with Down syndrome, in whom a 10- to 20-fold
increased risk of leukemogenesis has been reported compared with children without
Down syndrome. We explored the association between medical test irradiation, a
postulated leukemogenic agent, and acute leukemia among children with Down
syndrome. PATIENTS AND METHODS: Children with Down syndrome (controls) were
frequency matched on age to children with Down syndrome and leukemia (cases)
diagnosed at ages 0 to 19 years during the period 1997-2002 at participating
Children's Oncology Group institutions in North America. Telephone interviews
were completed with mothers of 158 cases (n = 97 acute lymphoblastic leukemia and
n = 61 acute myeloid leukemia) and 173 controls. Paternal interviews were
completed with 275 fathers and 40 mothers serving as surrogates. Three
irradiation exposure periods were examined: preconception, in utero, and
postnatal. Multivariate unconditional logistic regression models were constructed
to evaluate the associations of interest, resulting in odds ratios and 95%
confidence intervals. RESULTS: There was little evidence that maternal or
paternal preconception irradiation exposure, intrauterine exposure, or postnatal
exposure contributes to leukemogenesis in children with Down syndrome. Overall,
no evidence for an effect of any periconceptional exposure was observed. Similar
results were observed among acute lymphoblastic leukemia and acute myeloid
leukemia cases analyzed separately. CONCLUSIONS: This was the first study, to our
knowledge, to examine such an association among this unique patient population.
The results do not provide evidence of a positive association between ionizing
radiation exposure and acute leukemia among children with Down syndrome. The
absence of an association should be encouraging for concerned parents of children
with Down syndrome who undergo a series of diagnostic radiographs in the course
of their standard care.
PMID- 17030599
TI - Gastrointestinal tract involvement in Langerhans cell histiocytosis: case report
and literature review.
AB - Digestive tract involvement in Langerhans cell histiocytosis is exceedingly rare.
We report a case of Langerhans cell histiocytosis in an otherwise thriving
neonate presenting with hematochezia, anemia, and rash. We also review the few
cases of Langerhans cell histiocytosis with gastrointestinal involvement reported
in the English-language medical literature. Although gastrointestinal involvement
can range in severity from mild to life-threatening, its presence may be
indicative of multisystemic disease, and aggressive treatment should be
considered.
PMID- 17030600
TI - The CDM superfamily protein MBC directs myoblast fusion through a mechanism that
requires phosphatidylinositol 3,4,5-triphosphate binding but is independent of
direct interaction with DCrk.
AB - Myoblast city (mbc), a member of the CDM superfamily, is essential in the
Drosophila melanogaster embryo for fusion of myoblasts into multinucleate fibers.
Using germ line clones in which both maternal and zygotic contributions were
eliminated and rescue of the zygotic loss-of-function phenotype, we established
that mbc is required in the fusion-competent subset of myoblasts. Along with its
close orthologs Dock180 and CED-5, MBC has an SH3 domain at its N terminus,
conserved internal domains termed DHR1 and DHR2 (or "Docker"), and C-terminal
proline-rich domains that associate with the adapter protein DCrk. The importance
of these domains has been evaluated by the ability of MBC mutations and deletions
to rescue the mbc loss-of-function muscle phenotype. We demonstrate that the SH3
and Docker domains are essential. Moreover, ethyl methanesulfonate-induced
mutations that change amino acids within the MBC Docker domain to residues that
are conserved in other CDM family members nevertheless eliminate MBC function in
the embryo, which suggests that these sites may mediate interactions specific to
Drosophila MBC. A functional requirement for the conserved DHR1 domain, which
binds to phosphatidylinositol 3,4,5-triphosphate, implicates phosphoinositide
signaling in myoblast fusion. Finally, the proline-rich C-terminal sites mediate
strong interactions with DCrk, as expected. These sites are not required for MBC
to rescue the muscle loss-of-function phenotype, however, which suggests that
MBC's role in myoblast fusion can be carried out independently of direct DCrk
binding.
PMID- 17030601
TI - Smc5/6 is required for repair at collapsed replication forks.
AB - In eukaryotes, three pairs of structural-maintenance-of-chromosome (SMC) proteins
are found in conserved multisubunit protein complexes required for chromosomal
organization. Cohesin, the Smc1/3 complex, mediates sister chromatid cohesion
while two condensin complexes containing Smc2/4 facilitate chromosome
condensation. Smc5/6 scaffolds an essential complex required for homologous
recombination repair. We have examined the response of smc6 mutants to the
inhibition of DNA replication. We define homologous recombination-dependent and
independent functions for Smc6 during replication inhibition and provide evidence
for a Rad60-independent function within S phase, in addition to a Rad60-dependent
function following S phase. Both genetic and physical data show that when forks
collapse (i.e., are not stabilized by the Cds1Chk2 checkpoint), Smc6 is required
for the effective repair of resulting lesions but not for the recruitment of
recombination proteins. We further demonstrate that when the Rad60-dependent,
post-S-phase Smc6 function is compromised, the resulting recombination-dependent
DNA intermediates that accumulate following release from replication arrest are
not recognized by the G2/M checkpoint.
PMID- 17030602
TI - Cell confluence regulates hepatocyte growth factor-stimulated cell morphogenesis
in a beta-catenin-dependent manner.
AB - Following organ injury, morphogenic epithelial responses can vary depending on
local cell density. In the present study, the role of cell confluence in
determining the responsiveness of renal epithelial cells to the dedifferentiating
morphogenic signals of hepatocyte growth factor (HGF) was examined. Increasing
confluence resulted in a greater tendency of cells to organize into epithelial
tubes and a significant decrease in migratory responsiveness to HGF. Analysis of
downstream signaling revealed that the HGF receptor c-Met was equally activated
in confluent and nonconfluent cells following HGF stimulation but that
phosphoinositide 3-kinase-dependent activation of Akt and Rac were selectively
diminished in confluent cells. In nonconfluent cells treated with HGF, the high
level of Akt activation resulted in inhibitory phosphorylation of glycogen
synthase kinase 3beta (GSK-3beta) and increased beta-catenin nuclear signaling.
In contrast, confluent cells, in which HGF-stimulated Akt activation was
diminished, displayed less inhibitory phosphorylation of GSK-3beta and less
nuclear signaling by beta-catenin. Overexpression of beta-catenin (SA), which
cannot be phosphorylated by GSK-3beta and targeted for ubiquitination,
significantly increased migration in fully confluent cells. Thus, cells
maintained at high confluence selectively downregulate signaling events such as
Rac activation and beta-catenin-dependent transcription that would otherwise
promote cell dedifferentiation and migration.
PMID- 17030603
TI - The Drosophila histone acetyltransferase Gcn5 and transcriptional adaptor Ada2a
are involved in nucleosomal histone H4 acetylation.
AB - The histone acetyltransferase (HAT) Gcn5 plays a role in chromatin structure and
gene expression regulation as a catalytic component of multiprotein complexes,
some of which also contain Ada2-type transcriptional coactivators. Data obtained
mostly from studies on yeast (Saccharomyces cerevisiae) suggest that Ada2
potentiates Gcn5 activity and substrate recognition. dAda2b, one of two related
Ada2 proteins of Drosophila melanogaster, was recently found to play a role in
complexes acetylating histone 3 (H3). Evidence of an in vivo functional link
between the related coactivator dAda2a and dGcn5, however, is lacking. Here we
present data on the genetic interaction of dGcn5 and dAda2a. The loss of either
dGcn5 or dAda2a function results in similar chromosome structural and
developmental defects. In dAda2a mutants, the nucleosomal H4 acetylation at
lysines 12 and 5 is significantly reduced, while the acetylation established by
dAda2b-containing Gcn5 complexes at H3 lysines 9 and 14 is unaffected. The data
presented here, together with our earlier data on the function of dAda2b, provide
evidence that related Ada2 proteins of Drosophila, together with Gcn5 HAT, are
involved in the acetylation of specific lysine residues in the N-terminal tails
of nucleosomal H3 and H4. Our data suggest dAda2a involvement in both uniformly
distributed H4 acetylation and gene-specific transcription regulation.
PMID- 17030604
TI - Evidence that the transcription elongation function of Rpb9 is involved in
transcription-coupled DNA repair in Saccharomyces cerevisiae.
AB - Rpb9, a small nonessential subunit of RNA polymerase II, has been shown to have
multiple transcription-related functions in Saccharomyces cerevisiae. These
functions include promoting transcription elongation and mediating a subpathway
of transcription-coupled repair (TCR) that is independent of Rad26, the homologue
of human Cockayne syndrome complementation group B protein. Rpb9 is composed of
three distinct domains: the N-terminal Zn1, the C-terminal Zn2, and the central
linker. Here we show that the Zn1 and linker domains are essential, whereas the
Zn2 domain is almost dispensable, for both transcription elongation and TCR
functions. Impairment of transcription elongation, which does not dramatically
compromise Rad26-mediated TCR, completely abolishes Rpb9-mediated TCR.
Furthermore, Rpb9 appears to be dispensable for TCR if its transcription
elongation function is compensated for by removing a transcription
repression/elongation factor. Our data suggest that the transcription elongation
function of Rpb9 is involved in TCR.
PMID- 17030605
TI - Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor
metastasis.
AB - The insulin receptor substrate (IRS) proteins are cytoplasmic adaptors that
organize signaling complexes downstream of activated cell surface receptors.
Here, we show that IRS-1 and IRS-2, despite significant homology, play critical
yet distinct functions in breast cancer, and we identify specific signaling
pathways that are influenced by IRS-1 using the polyoma virus middle-T (PyV-MT)
transgenic mouse model of mammary carcinoma and Irs-1 null (Irs1(-/-)) mice. The
absence of Irs-1 expression enhanced metastatic spread significantly without a
significant effect on primary tumor growth. Orthotopic transplant studies
revealed that the increased metastatic potential of Irs1-deficient tumor cells is
cell autonomous. Mammary tumors that developed in PyV-MT::Irs1(-/-) mice
exhibited elevated Irs-2 function and enhanced phosphatidylinositol 3
kinase/Akt/mTor activity, suggesting that one mechanism by which Irs-1 impedes
metastasis is to suppress Irs-2-dependent signaling. In support of this
mechanism, reduction of Irs-2 expression in Irs1(-/-) tumor cells restored mTor
signaling to wild-type levels. PyV-MT::Irs1(-/-) tumors also exhibited a
significant increase in vascular endothelial growth factor expression and
microvessel density, which could facilitate their dissemination. The significance
of our findings for human breast cancer is heightened by our observation that Irs
1 is inactivated in wild-type, metastatic mammary tumors by serine
phosphorylation. Collectively, our findings reveal that inactivation of IRS-1
enhances breast cancer metastasis and support the novel hypothesis that IRS-1 has
metastasis suppressor functions for breast cancer.
PMID- 17030606
TI - The mitogen-activated protein kinase (MAPK)-activated protein kinases MK2 and MK3
cooperate in stimulation of tumor necrosis factor biosynthesis and stabilization
of p38 MAPK.
AB - MK2 and MK3 represent protein kinases downstream of p38 mitogen-activated protein
kinase (MAPK). Deletion of the MK2 gene in mice resulted in an impaired
inflammatory response although MK3, which displays extensive structural
similarities and identical functional properties in vitro, is still present.
Here, we analyze tumor necrosis factor (TNF) production and expression of p38
MAPK and tristetraprolin (TTP) in MK3-deficient mice and demonstrate that there
are no significant differences with wild-type animals. We show that in vivo MK2
and MK3 are expressed and activated in parallel. However, the level of activity
of MK2 is always significantly higher than that of MK3. Accordingly, we
hypothesized that MK3 could have significant effects only in an MK2-free
background and generated MK2/MK3 double-knockout mice. Unexpectedly, these mice
are viable and show no obvious defects due to loss of compensation between MK2
and MK3. However, there is a further reduction of TNF production and expression
of p38 and TTP in double-knockout mice compared to MK2-deficient mice. This
finding, together with the observation that ectopically expressed MK3 can rescue
MK2 deficiency similarly to MK2, indicates that both kinases share the same
physiological function in vivo but are expressed to different levels.
PMID- 17030607
TI - The rad51-K191R ATPase-defective mutant is impaired for presynaptic filament
formation.
AB - The nucleoprotein filament formed by Rad51 polymerization on single-stranded DNA
is essential for homologous pairing and strand exchange. ATP binding is required
for Rad51 nucleoprotein filament formation and strand exchange, but ATP
hydrolysis is not required for these functions in vitro. Previous studies have
shown that a yeast strain expressing the rad51-K191R allele is sensitive to
ionizing radiation, suggesting an important role for ATP hydrolysis in vivo. The
recruitment of Rad51-K191R to double-strand breaks is defective in vivo, and this
phenotype can be suppressed by elimination of the Srs2 helicase, an antagonist of
Rad51 filament formation. The phenotype of the rad51-K191R strain is also
suppressed by overexpression of Rad54. In vitro, the Rad51-K191R protein exhibits
a slight decrease in binding to DNA, consistent with the defect in presynaptic
filament formation. However, the rad51-K191R mutation is dominant in heterozygous
diploids, indicating that the defect is not due simply to reduced affinity for
DNA. We suggest the Rad51-K191R protein either forms an altered filament or is
defective in turnover, resulting in a reduced pool of free protein available for
DNA binding.
PMID- 17030608
TI - BRF1 protein turnover and mRNA decay activity are regulated by protein kinase B
at the same phosphorylation sites.
AB - BRF1 posttranscriptionally regulates mRNA levels by targeting ARE-bearing
transcripts to the decay machinery. We previously showed that protein kinase B
(PKB) phosphorylates BRF1 at Ser92, resulting in binding to 14-3-3 and impairment
of mRNA decay activity. Here we identify an additional regulatory site at Ser203
that cooperates in vivo with Ser92. In vitro kinase labeling and wortmannin
sensitivity indicate that Ser203 phosphorylation is also performed by PKB.
Mutation of both serines to alanine uncouples BRF1 from PKB regulation, leading
to constitutive mRNA decay even in the presence of stabilizing signals. BRF1
protein is labile because of proteasomal degradation (half-life, <3 h) but
becomes stabilized upon phosphorylation and is less stable in PKBalpha(-/-)
cells. Surprisingly, phosphorylation-dependent protein stability is also
regulated by Ser92 and Ser203, with parallel phosphorylation required at these
sites. Phosphorylation-dependent binding to 14-3-3 is abolished only when both
sites are mutated. Cell compartment fractionation experiments support a model in
which binding to 14-3-3 sequesters BRF1 through relocalization and prevents it
from executing its mRNA decay activity, as well as from proteasomal degradation,
thereby maintaining high BRF1 protein levels that are required to reinstate decay
upon dissipation of the stabilizing signal.
PMID- 17030609
TI - Complex formation with Rev1 enhances the proficiency of Saccharomyces cerevisiae
DNA polymerase zeta for mismatch extension and for extension opposite from DNA
lesions.
AB - Rev1, a Y family DNA polymerase (Pol) functions together with Polzeta, a B family
Pol comprised of the Rev3 catalytic subunit and Rev7 accessory subunit, in
promoting translesion DNA synthesis (TLS). Extensive genetic studies with
Saccharomyces cerevisiae have indicated a requirement of both Polzeta and Rev1
for damage-induced mutagenesis, implicating their involvement in mutagenic TLS.
Polzeta is specifically adapted to promote the extension step of lesion bypass,
as it proficiently extends primer termini opposite DNA lesions, and it is also a
proficient extender of mismatched primer termini on undamaged DNAs. Since TLS
through UV-induced lesions and various other DNA lesions does not depend upon the
DNA-synthetic activity of Rev1, Rev1 must contribute to Polzeta-dependent TLS in
a nonenzymatic way. Here, we provide evidence for the physical association of
Rev1 with Polzeta and show that this binding is mediated through the C terminus
of Rev1 and the polymerase domain of Rev3. Importantly, a rev1 mutant that lacks
the C-terminal 72 residues which inactivate interaction with Rev3 exhibits the
same high degree of UV sensitivity and defectiveness in UV-induced mutagenesis as
that conferred by the rev1Delta mutation. We propose that Rev1 binding to Polzeta
is indispensable for the targeting of Polzeta to the replication fork stalled at
a DNA lesion. In addition to this structural role, Rev1 binding enhances the
proficiency of Polzeta for the extension of mismatched primer termini on
undamaged DNAs and for the extension of primer termini opposite DNA lesions.
PMID- 17030610
TI - Differential recruitment of methylated CpG binding domains by the orphan receptor
GCNF initiates the repression and silencing of Oct4 expression.
AB - The pluripotent factor Oct4 is a key transcription factor that maintains
embryonic stem (ES) cell self-renewal and is down-regulated upon the
differentiation of ES cells and silenced in somatic cells. A combination of cis
elements, transcription factors, and epigenetic modifications, such as DNA
methylation, are involved in the regulation of Oct4 gene expression. Here we show
that the orphan nuclear receptor GCNF initiates Oct4 repression and DNA
methylation by the differential recruitment of MBD (methylated CpG binding
domain) factors to the promoter. Compared with wild-type ES cells and
gastrulating embryos, Oct4 repression is lost and its proximal promoter is
significantly hypomethylated in RA-differentiated GCNF(-/-) ES cells. The Oct4
gene is reexpressed in some somatic cells of GCNF(-/-) embryos, showing that it
has not been properly silenced coincident with reduced DNA methylation of its
promoter. Efforts to characterize mediators of GCNF's repressive function and DNA
methylation of the Oct4 promoter identified methyl-DNA binding proteins, MBD3 and
MBD2, as GCNF-interacting factors. In P19 and ES cells, upon differentiation,
endogenous GCNF binds to the Oct4 proximal promoter and differentially recruits
MBD3 and MBD2. In differentiated GCNF(-/-) ES cells, recruitment of MBD3 and MBD2
to the Oct4 promoter is lost, and repression of Oct4 expression and DNA
methylation fails to occur. RNA interference-mediated knockdown of MBD3 and/or
MBD2 expression results in reduced Oct4 repression in differentiated P19 and ES
cells. Repression of Oct4 expression and recruitment of MBD3 are maintained in de
novo DNA methylation-deficient ES cells (Dnmt3A/3B-null cells), while MBD2
recruitment is lost. Thus, recruitment of MBD3 and MBD2 by GCNF links two events,
gene-specific repression and DNA methylation, which occur differentially at the
Oct4 promoter. GCNF initiates the repression and epigenetic modification of Oct4
gene during ES cell differentiation.
PMID- 17030611
TI - Autophagy is activated for cell survival after endoplasmic reticulum stress.
AB - Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic
reticulum (ER) by the unfolded protein response, involving the induction of
molecular chaperones, translational attenuation, and ER-associated degradation,
to prevent cell death. Here, we found that the autophagy system is activated as a
novel signaling pathway in response to ER stress. Treatment of SK-N-SH
neuroblastoma cells with ER stressors markedly induced the formation of
autophagosomes, which were recognized at the ultrastructural level. The formation
of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 "dots"),
representing autophagosomes, was extensively induced in cells exposed to ER
stress with conversion from LC3-I to LC3-II. In IRE1-deficient cells or cells
treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER
stress was inhibited, indicating that the IRE1-JNK pathway is required for
autophagy activation after ER stress. In contrast, PERK-deficient cells and ATF6
knockdown cells showed that autophagy was induced after ER stress in a manner
similar to the wild-type cells. Disturbance of autophagy rendered cells
vulnerable to ER stress, suggesting that autophagy plays important roles in cell
survival after ER stress.
PMID- 17030612
TI - Acm1 is a negative regulator of the CDH1-dependent anaphase-promoting
complex/cyclosome in budding yeast.
AB - Cdh1 is a coactivator of the anaphase-promoting complex/cyclosome (APC/C) and
contributes to mitotic exit and G1 maintenance by facilitating the
polyubiquitination and subsequent proteolysis of specific substrates. Here, we
report that budding yeast Cdh1 is a component of a cell cycle-regulated complex
that includes the 14-3-3 homologs Bmh1 and Bmh2 and a previously uncharacterized
protein, which we name Acm1 (APC/CCdh1 modulator 1). Association of Cdh1 with
Bmh1 and Bmh2 requires Acm1, and the Acm1 protein is cell cycle regulated,
appearing late in G1 and disappearing in late M. In acm1Delta strains, Cdh1
localization to the bud neck and association with two substrates, Clb2 and Hsl1,
were strongly enhanced. Several lines of evidence suggest that Acm1 can suppress
APC/CCdh1-mediated proteolysis of mitotic cyclins. First, overexpression of Acm1
fully restored viability to cells expressing toxic levels of Cdh1 or a
constitutively active Cdh1 mutant lacking inhibitory phosphorylation sites.
Second, overexpression of Acm1 was toxic in sic1Delta cells. Third, ACM1 deletion
exacerbated a low-penetrance elongated-bud phenotype caused by modest
overexpression of Cdh1. This bud elongation was independent of the morphogenesis
checkpoint, and the combination of acm1Delta and hsl1Delta resulted in a dramatic
enhancement of bud elongation and G2/M delay. Effects on bud elongation were
attenuated when Cdh1 was replaced with a mutant lacking the C-terminal IR
dipeptide, suggesting that APC/C-dependent proteolysis is required for this
phenotype. We propose that Acm1 and Bmh1/Bmh2 constitute a specialized inhibitor
of APC/CCdh1.
PMID- 17030613
TI - Perk-dependent translational regulation promotes tumor cell adaptation and
angiogenesis in response to hypoxic stress.
AB - It has been well established that the tumor microenvironment can promote tumor
cell adaptation and survival. However, the mechanisms that influence malignant
progression have not been clearly elucidated. We have previously demonstrated
that cells cultured under hypoxic/anoxic conditions and transformed cells in
hypoxic areas of tumors activate a translational control program known as the
integrated stress response (ISR). Here, we show that tumors derived from K-Ras
transformed Perk(-/-) mouse embryonic fibroblasts (MEFs) are smaller and exhibit
less angiogenesis than tumors with an intact ISR. Furthermore, Perk promotes a
tumor microenvironment that favors the formation of functional microvessels.
These observations were corroborated by a microarray analysis of polysome-bound
RNA in aerobic and hypoxic Perk(+/+) and Perk(-/-) MEFs. This analysis revealed
that a subset of proangiogenic transcripts is preferentially translated in a Perk
dependent manner; these transcripts include VCIP, an adhesion molecule that
promotes cellular adhesion, integrin binding, and capillary morphogenesis. Taken
with the concomitant Perk-dependent translational induction of additional
proangiogenic genes identified by our microarray analysis, this study suggests
that Perk plays a role in tumor cell adaptation to hypoxic stress by regulating
the translation of angiogenic factors necessary for the development of functional
microvessels and further supports the contention that the Perk pathway could be
an attractive target for novel antitumor modalities.
PMID- 17030614
TI - Profile of histone lysine methylation across transcribed mammalian chromatin.
AB - Complex patterns of histone lysine methylation encode distinct functions within
chromatin. We previously reported that trimethylation of lysine 9 of histone H3
(H3K9) occurs at both silent heterochromatin and at the transcribed regions of
active mammalian genes, suggesting that the extent of histone lysine methylation
involved in mammalian gene activation is not completely defined. To identify
additional sites of histone methylation that respond to mammalian gene activity,
we describe here a comparative assessment of all six known positions of histone
lysine methylation and relate them to gene transcription. Using several model
loci, we observed high trimethylation of H3K4, H3K9, H3K36, and H3K79 in the
transcribed region, consistent with previous findings. We identify H4K20
monomethylation, a modification previously linked with repression, as a mark of
transcription elongation in mammalian cells. In contrast, H3K27 monomethylation,
a modification enriched at pericentromeric heterochromatin, was observed broadly
distributed throughout all euchromatic sites analyzed, with selective depletion
in the vicinity of the transcription start sites at active genes. Together, these
results underscore that similar to other described methyl-lysine modifications,
H4K20 and H3K27 monomethylation are versatile and dynamic with respect to gene
activity, suggesting the existence of novel site-specific methyltransferases and
demethylases coupled to the transcription cycle.
PMID- 17030615
TI - The DEK nuclear autoantigen is a secreted chemotactic factor.
AB - The nuclear DNA-binding protein DEK is an autoantigen that has been implicated in
the regulation of transcription, chromatin architecture, and mRNA processing. We
demonstrate here that DEK is actively secreted by macrophages and is also found
in synovial fluid samples from patients with juvenile arthritis. Secretion of DEK
is modulated by casein kinase 2, stimulated by interleukin-8, and inhibited by
dexamethasone and cyclosporine A, consistent with a role as a proinflammatory
molecule. DEK is secreted in both a free form and in exosomes, vesicular
structures in which transcription-modulating factors such as DEK have not
previously been found. Furthermore, DEK functions as a chemotactic factor,
attracting neutrophils, CD8+ T lymphocytes, and natural killer cells. Therefore,
the DEK autoantigen, previously described as a strictly nuclear protein, is
secreted and can act as an extracellular chemoattractant, suggesting a direct
role for DEK in inflammation.
PMID- 17030616
TI - HSP70 induction by ING proteins sensitizes cells to tumor necrosis factor alpha
receptor-mediated apoptosis.
AB - ING proteins affect apoptosis, growth, and DNA repair by transducing stress
signals such as DNA damage, binding histones, and subsequently regulating
chromatin structure and p53 activity. p53 target genes, including the p21 cyclin
dependent kinase inhibitor and Bax, an inducer of apoptosis, are regulated by ING
proteins. To identify additional targets downstream of p33ING1 and p32ING2, cDNA
microarrays were performed on phenotypically normal human primary fibroblasts.
The 0.36% of genes affected by ING proteins in primary fibroblasts were distinct
from targets seen in established cells and included the HSP70 heat shock gene,
whose promoter was specifically induced >10-fold. ING1-induced expression of
HSP70 shifted cells from survival to a death pathway in response to tumor
necrosis factor alpha (TNF-alpha), and p33ING1b protein showed synergy with TNF
alpha in inducing apoptosis, which correlated with reduced NF-kappaB-dependent
transcription. These findings are consistent with previous reports that HSP70
promotes TNF-alpha-mediated apoptosis by binding I-kappaBeta kinase gamma and
impairing NF-kappaB survival signaling. Induction of HSP70 required the amino
terminus of ING1b but not the plant homeodomain region that was recently
identified as a histone binding domain. Regulation of HSP70 gene expression by
the ING tumor suppressors provides a novel link between the INGs and the stress
regulated NF-kappaB survival pathway important in hypoxia and angiogenesis.
PMID- 17030617
TI - Cripto binds transforming growth factor beta (TGF-beta) and inhibits TGF-beta
signaling.
AB - Cripto is a developmental oncoprotein and a member of the epidermal growth factor
Cripto, FRL-1, Cryptic family of extracellular signaling molecules. In addition
to having essential functions during embryogenesis, Cripto is highly expressed in
tumors and promotes tumorigenesis. During development, Cripto acts as an obligate
coreceptor for transforming growth factor beta (TGF-beta) ligands, including
nodals, growth and differentiation factor 1 (GDF1), and GDF3. As an oncogene,
Cripto is thought to promote tumor growth via mechanisms including activation of
mitogenic signaling pathways and antagonism of activin signaling. Here, we
provide evidence supporting a novel mechanism in which Cripto inhibits the tumor
suppressor function of TGF-beta. Cripto bound TGF-beta and reduced the
association of TGF-beta with its type I receptor, TbetaRI. Consistent with its
ability to block receptor assembly, Cripto suppressed TGF-beta signaling in
multiple cell types and diminished the cytostatic effects of TGF-beta in mammary
epithelial cells. Furthermore, targeted disruption of Cripto expression by use of
small inhibitory RNA enhanced TGF-beta signaling, indicating that endogenous
Cripto plays a role in restraining TGF-beta responses.
PMID- 17030618
TI - Timing and sequence requirements defined for embryonic maintenance of imprinted
DNA methylation at Rasgrf1.
AB - Epigenetic programming is critical for normal development of mammalian embryos.
Errors cause misexpression of genes and aberrant development (E. Li, C. Beard,
and R. Jaenisch, Nature 366:362-365, 1993). Imprinted genes are important targets
of epigenetic regulation, but little is known about how the epigenetic patterns
are established in the parental germ lines and maintained in the embryo. Paternal
allele-specific expression at the imprinted Rasgrf1 locus in mice is controlled
by paternal allele-specific methylation at a differentially methylated domain
(DMD). DMD methylation is in turn controlled by a direct repeat sequence
immediately downstream of the DMD which is required for establishing Rasgrf1
methylation in the male germ line (B. J. Yoon et al., Nat. Genet. 30:92-96,
2002). To determine if these repeats have a role in methylation maintenance, we
developed a conditional deletion of the repeat sequence in mice and showed that
the repeats are also required during a narrow interval to maintain paternal
methylation of Rasgrf1 in developing embryos. Removing the repeats upon
fertilization caused a total loss of methylation by the morula stage, but by the
epiblast stage, the repeats were completely dispensable for methylation
maintenance. This developmental interval coincides with genome-wide demethylation
and remethylation in mice which most imprinted genes resist. Our data show that
the Rasgrf1 repeats serve at least two functions: first, to establish Rasgrf1 DNA
methylation in the male germ line, and second, to resist global demethylation in
the preimplantation embryo.
PMID- 17030620
TI - Novel mRNA targets for tristetraprolin (TTP) identified by global analysis of
stabilized transcripts in TTP-deficient fibroblasts.
AB - Tristetraprolin (TTP) is a tandem CCCH zinc finger protein that was identified
through its rapid induction by mitogens in fibroblasts. Studies of TTP-deficient
mice and cells derived from them showed that TTP could bind to certain AU-rich
elements in mRNAs, leading to increases in the rates of mRNA deadenylation and
destruction. Known physiological target mRNAs for TTP include tumor necrosis
factor alpha, granulocyte-macrophage colony-stimulating factor, and interleukin
2beta. Here we used microarray analysis of RNA from wild-type and TTP-deficient
fibroblast cell lines to identify transcripts with different decay rates, after
serum stimulation and actinomycin D treatment. Of 250 mRNAs apparently stabilized
in the absence of TTP, 23 contained two or more conserved TTP binding sites; nine
of these appeared to be stabilized on Northern blots. The most dramatically
affected transcript encoded the protein Ier3, recently implicated in the
physiological control of blood pressure. The Ier3 transcript contained several
conserved TTP binding sites that could bind TTP directly and conferred TTP
sensitivity to the mRNA in cell transfection studies. These studies have
identified several new, physiologically relevant TTP target transcripts in
fibroblasts; these target mRNAs encode proteins from a variety of functional
classes.
PMID- 17030619
TI - Essential role of phospholipase C gamma 2 in early B-cell development and Myc
mediated lymphomagenesis.
AB - Phospholipase Cgamma2 (PLCgamma2) is a critical signaling effector of the B-cell
receptor (BCR). Here we show that PLCgamma2 deficiency impedes early B-cell
development, resulting in an increase of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large
pre-B cells. PLCgamma2 deficiency impairs pre-BCR-mediated functions, leading to
enhanced interleukin-7 (IL-7) signaling and elevated levels of RAGs in the
selected large pre-B cells. Consequently, PLCgamma2 deficiency renders large pre
B cells susceptible to transformation, resulting in dramatic acceleration of Myc
induced lymphomagenesis. PLCgamma2(-/-) Emu-Myc transgenic mice mainly develop
lymphomas of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large pre-B-cell origin, which are
uncommon in wild-type Emu-Myc transgenics. Furthermore, lymphomas from PLCgamma2(
/-) Emu-Myc transgenic mice exhibited a loss of p27Kip1 and often displayed
alterations in Arf or p53. Thus, PLCgamma2 plays an important role in pre-BCR
mediated early B-cell development, and its deficiency leads to markedly increased
pools of the most at-risk large pre-B cells, which display hyperresponsiveness to
IL-7 and express high levels of RAGs, making them prone to secondary mutations
and Myc-induced malignancy.
PMID- 17030621
TI - Loss of Hsp90 association up-regulates Src-dependent ErbB2 activity.
AB - The receptor tyrosine kinase ErbB2 plays a crucial role in tumorigenesis. We
showed previously that the molecular chaperone Hsp90 protects ErbB2 from
proteasome-mediated degradation by binding to a short loop structure in the N
lobe of the kinase domain. Here we show that loss of Hsp90 binding correlates
with enhanced ErbB2 kinase activity and its transactivating potential,
concomitant with constitutively increased phosphorylation of Tyr877, located in
the activation loop of the kinase domain. We show further that Tyr877
phosphorylation is mediated by Src and that it is necessary for the enhanced
kinase activity of ErbB2. Finally, computer modeling of the kinase domain
suggests a phosphorylation-dependent reorientation of the activation loop,
denoting the importance of Tyr877 phosphorylation for ErbB2 activity. These
findings suggest that Hsp90 binding to ErbB2 participates in regulation of kinase
activity as well as kinase stability.
PMID- 17030622
TI - Cbln1 is essential for interaction-dependent secretion of Cbln3.
AB - Cbln1 and the orphan glutamate receptor GluRdelta2 are pre- and postsynaptic
components, respectively, of a novel transneuronal signaling pathway regulating
synapse structure and function. We show here that Cbln1 is secreted from
cerebellar granule cells in complex with a related protein, Cbln3. However, cbln1
and cbln3-null mice have different phenotypes and cbln1 cbln3 double-null mice
have deficits identical to those of cbln1 knockout mice. The basis for these
discordant phenotypes is that Cbln1 and Cbln3 reciprocally regulate each other's
degradation and secretion such that cbln1-null mice lack both Cbln1 and Cbln3,
whereas cbln3-null mice lack Cbln3 but have an approximately sixfold increase in
Cbln1. Unlike Cbln1, Cbln3 cannot form homomeric complexes and is secreted only
when bound to Cbln1. Structural modeling and mutation analysis reveal that, by
constituting a steric clash that is masked upon binding Cbln1 in a "hide-and-run"
mechanism of endoplasmic reticulum retention, a single arginine confers the
unique properties of Cbln3.
PMID- 17030623
TI - Imp associates with squid and Hrp48 and contributes to localized expression of
gurken in the oocyte.
AB - Localization and translational control of Drosophila melanogaster gurken and
oskar mRNAs rely on the hnRNP proteins Squid and Hrp48, which are complexed with
one another in the ovary. Imp, the Drosophila homolog of proteins acting in
localization of mRNAs in other species, is also associated with Squid and Hrp48.
Notably, Imp is concentrated at sites of gurken and oskar mRNA localization in
the oocyte, and alteration of gurken localization also alters Imp distribution.
Imp binds gurken mRNA with high affinity in vitro; thus, the colocalization with
gurken mRNA in vivo is likely to be the result of direct binding. Imp mutants
support apparently normal regulation of gurken and oskar mRNAs. However, loss of
Imp activity partially suppresses a gurken misexpression phenotype, indicating
that Imp does act in control of gurken expression but has a largely redundant
role that is only revealed when normal gurken expression is perturbed.
Overexpression of Imp disrupts localization of gurken mRNA as well as
localization and translational regulation of oskar mRNA. The opposing effects of
reduced and elevated Imp activity on gurken mRNA expression indicate a role in
gurken mRNA regulation.
PMID- 17030625
TI - AUF1 cell cycle variations define genomic DNA methylation by regulation of DNMT1
mRNA stability.
AB - DNA methylation is a major determinant of epigenetic inheritance. DNA
methyltransferase 1 (DNMT1) is the enzyme responsible for the maintenance of DNA
methylation patterns during cell division, and deregulated expression of DNMT1
leads to cellular transformation. We show herein that AU-rich element/poly(U)
binding/degradation factor 1 (AUF1)/heterogeneous nuclear ribonucleoprotein D
interacts with an AU-rich conserved element in the 3' untranslated region of the
DNMT1 mRNA and targets it for destabilization by the exosome. AUF1 protein levels
are regulated by the cell cycle by the proteasome, resulting in cell cycle
specific destabilization of DNMT1 mRNA. AUF1 knock down leads to increased DNMT1
expression and modifications of cell cycle kinetics, increased DNA
methyltransferase activity, and genome hypermethylation. Concurrent AUF1 and
DNMT1 knock down abolishes this effect, suggesting that the effects of AUF1 knock
down on the cell cycle are mediated at least in part by DNMT1. In this study, we
demonstrate a link between AUF1, the RNA degradation machinery, and maintenance
of the epigenetic integrity of the cell.
PMID- 17030624
TI - ATM and ATR pathways signal alternative splicing of Drosophila TAF1 pre-mRNA in
response to DNA damage.
AB - Alternative pre-mRNA splicing is a major mechanism utilized by eukaryotic
organisms to expand their protein-coding capacity. To examine the role of cell
signaling in regulating alternative splicing, we analyzed the splicing of the
Drosophila melanogaster TAF1 pre-mRNA. TAF1 encodes a subunit of TFIID, which is
broadly required for RNA polymerase II transcription. We demonstrate that TAF1
alternative splicing generates four mRNAs, TAF1-1, TAF1-2, TAF1-3, and TAF1-4, of
which TAF1-2 and TAF1-4 encode proteins that directly bind DNA through AT hooks.
TAF1 alternative splicing was regulated in a tissue-specific manner and in
response to DNA damage induced by ionizing radiation or camptothecin.
Pharmacological inhibitors and RNA interference were used to demonstrate that
ionizing-radiation-induced upregulation of TAF1-3 and TAF1-4 splicing in S2 cells
was mediated by the ATM (ataxia-telangiectasia mutated) DNA damage response
kinase and checkpoint kinase 2 (CHK2), a known ATM substrate. Similarly,
camptothecin-induced upregulation of TAF1-3 and TAF1-4 splicing was mediated by
ATR (ATM-RAD3 related) and CHK1. These findings suggest that inducible TAF1
alternative splicing is a mechanism to regulate transcription in response to
developmental or DNA damage signals and provide the first evidence that the
ATM/CHK2 and ATR/CHK1 signaling pathways control gene expression by regulating
alternative splicing.
PMID- 17030626
TI - A putative Arabidopsis nucleoporin, AtNUP160, is critical for RNA export and
required for plant tolerance to cold stress.
AB - To study the genetic control of plant responses to cold stress, Arabidopsis
thaliana mutants were isolated by a screen for mutations that impair cold-induced
transcription of the CBF3-LUC reporter gene. We report here the characterization
and cloning of a mutated gene, atnup160-1, which causes reduced CBF3-LUC
induction under cold stress. atnup160-1 mutant plants display altered cold
responsive gene expression and are sensitive to chilling stress and defective in
acquired freezing tolerance. AtNUP160 was isolated through positional cloning and
shown to encode a putative homolog of the animal nucleoporin Nup160. In addition
to the impaired expression of CBF genes, microarray analysis revealed that a
number of other genes important for plant cold tolerance were also affected in
the mutants. The atnup160 mutants flower early and show retarded seedling growth,
especially at low temperatures. AtNUP160 protein is localized at the nuclear rim,
and poly(A)-mRNA in situ hybridization shows that mRNA export is defective in the
atnup160-1 mutant plants. Our study suggests that Arabidopsis AtNUP160 is
critical for the nucleocytoplasmic transport of mRNAs and that it plays important
roles in plant growth and flowering time regulation and is required for cold
stress tolerance.
PMID- 17030627
TI - Neuromedin U receptor 2-deficient mice display differential responses in sensory
perception, stress, and feeding.
AB - Neuromedin U (NMU) is a highly conserved neuropeptide with a variety of
physiological functions mediated by two receptors, peripheral NMUR1 and central
nervous system NMUR2. Here we report the generation and phenotypic
characterization of mice deficient in the central nervous system receptor NMUR2.
We show that behavioral effects, such as suppression of food intake, enhanced
pain response, and excessive grooming induced by intracerebroventricular NMU
administration were abolished in the NMUR2 knockout (KO) mice, establishing a
causal role for NMUR2 in mediating NMU's central effects on these behaviors. In
contrast to the NMU peptide-deficient mice, NMUR2 KO mice appeared normal with
regard to stress, anxiety, body weight regulation, and food consumption. However,
the NMUR2 KO mice showed reduced pain sensitivity in both the hot plate and
formalin tests. Furthermore, facilitated excitatory synaptic transmission in
spinal dorsal horn neurons, a mechanism by which NMU stimulates pain, did not
occur in NMUR2 KO mice. These results provide significant insights into a
functional dissection of the differential contribution of peripherally or
centrally acting NMU system. They suggest that NMUR2 plays a more significant
role in central pain processing than other brain functions including
stress/anxiety and regulation of feeding.
PMID- 17030628
TI - Bone morphogenetic protein-induced MSX1 and MSX2 inhibit myocardin-dependent
smooth muscle gene transcription.
AB - During the onset and progression of atherosclerosis, the vascular smooth muscle
cell (VSMC) phenotype changes from differentiated to dedifferentiated, and in
some cases, this change is accompanied by osteogenic transition, resulting in
vascular calcification. One characteristic of dedifferentiated VSMCs is the down
regulation of smooth muscle cell (SMC) marker gene expression. Bone morphogenetic
proteins (BMPs), which are involved in the induction of osteogenic gene
expression, are detected in calcified vasculature. In this study, we found that
the BMP2-, BMP4-, and BMP6-induced expression of Msx transcription factors (Msx1
and Msx2) preceded the down-regulation of SMC marker expression in cultured
differentiated VSMCs. Either Msx1 or Msx2 markedly reduced the myocardin
dependent promoter activities of SMC marker genes (SM22alpha and caldesmon). We
further investigated interactions between Msx1 and myocardin/serum response
factor (SRF)/CArG-box motif (cis element for SRF) using coimmunoprecipitation,
gel-shift, and chromatin immunoprecipitation assays. Our results showed that Msx1
or Msx2 formed a ternary complex with SRF and myocardin and inhibited the binding
of SRF or SRF/myocardin to the CArG-box motif, resulting in inhibition of their
transcription.
PMID- 17030629
TI - Increased susceptibility to isoproterenol-induced cardiac hypertrophy and
impaired weight gain in mice lacking the histidine-rich calcium-binding protein.
AB - The sarcoplasmic reticulum (SR) plays a critical role in excitation-contraction
coupling by regulating the cytoplasmic calcium concentration of striated muscle.
The histidine-rich calcium-binding protein (HRCBP) is expressed in the junctional
SR, the site of calcium release from the SR. HRCBP is expressed exclusively in
muscle tissues and binds calcium with low affinity and high capacity. In
addition, HRCBP interacts with triadin, a protein associated with the ryanodine
receptor and thought to be involved in calcium release. Its calcium binding
properties, localization to the SR, and interaction with triadin suggest that
HRCBP is involved in calcium handling by the SR. To determine the function of
HRCBP in vivo, we inactivated HRC, the gene encoding HRCBP, in mice. HRC knockout
mice exhibited impaired weight gain beginning at 11 months of age, which was
marked by reduced skeletal muscle and fat mass, and triadin protein expression
was upregulated in the heart of HRC knockout mice. In addition, HRC null mice
displayed a significantly exaggerated response to the induction of cardiac
hypertrophy by isoproterenol compared to their wild-type littermates. The
exaggerated response of HRC knockout mice to the induction of cardiac hypertrophy
is consistent with a regulatory role for HRCBP in calcium handling in vivo and
suggests that mutations in HRC, in combination with other genetic or
environmental factors, might contribute to pathological hypertrophy and heart
failure.
PMID- 17030630
TI - Conservative inheritance of newly synthesized DNA in double-strand break-induced
gene conversion.
AB - To distinguish among possible mechanisms of repair of a double-strand break (DSB)
by gene conversion in budding yeast, Saccharomyces cerevisiae, we employed
isotope density transfer to analyze budding yeast mating type (MAT) gene
switching in G2/M-arrested cells. Both of the newly synthesized DNA strands
created during gene conversion are found at the repaired locus, leaving the donor
unchanged. These results support suggestions that mitotic DSBs are primarily
repaired by a synthesis-dependent strand-annealing mechanism. We also show that
the proportion of crossing-over associated with DSB-induced ectopic recombination
is not affected by the presence of nonhomologous sequences at one or both ends of
the DSB or the presence of additional sequences that must be copied from the
donor.
PMID- 17030632
TI - Editors and authors: a sacred trust.
PMID- 17030633
TI - Milestones in oncology: introducing a new section.
PMID- 17030631
TI - Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor
substrate 1 (IRS-1) or IRS-2.
AB - Insulin receptor substrates (IRSs) are signaling adaptors that play a major role
in the metabolic and mitogenic actions of insulin and insulin-like growth
factors. Reports have recently noted increased levels, or activity, of IRSs in
many human cancers, and some have linked this to poor patient prognosis. We found
that overexpressed IRS-1 was constitutively phosphorylated in vitro and in vivo
and that transgenic mice overexpressing IRS-1 or IRS-2 in the mammary gland
showed progressive mammary hyperplasia, tumorigenesis, and metastasis. Tumors
showed extensive squamous differentiation, a phenotype commonly seen with
activation of the canonical beta-catenin signaling pathway. Consistent with this,
IRSs were found to bind beta-catenin in vitro and in vivo. IRS-induced
tumorigenesis is unique, given that the IRSs are signaling adaptors with no
intrinsic kinase activity, and this supports a growing literature indicating a
role for IRSs in cancer. This study defines IRSs as oncogene proteins in vivo and
provides new models to develop inhibitors against IRSs for anticancer therapy.
PMID- 17030634
TI - The legacy of great science: the work of Nobel Laureate Gertrude Elion lives on.
PMID- 17030635
TI - Autobiography of Gertrude B. Elion, the Nobel Prize in Physiology or Medicine
1988.
PMID- 17030636
TI - The Colorectal Cancer Coalition: reflections on the future.
PMID- 17030637
TI - New approaches to the adjuvant therapy of colon cancer.
AB - Analysis of data from patients treated outside clinical trials suggests that
adjuvant chemotherapy for stage II colon cancer provides less than a 3% absolute
improvement in survival at 5 years. This is remarkably close to the small degree
of benefit suggested by controlled studies. An overview of the data suggests that
surgery alone cures approximately 75% of stage II patients. Between 20% and 25%
of patients experience disease recurrence despite surgery and adjuvant
chemotherapy, whereas adjuvant chemotherapy cures between 1% and 6%. In stage III
patients, the benefit of adjuvant therapy is greater overall. The extent of
benefit relates to tumor grade, invasion, and nodal involvement. Incorporation of
molecular markers in the design of current trials may enable us to refine our
identification of patients at highest risk of recurrence and hence those standing
to gain most from adjuvant therapy.
PMID- 17030638
TI - Therapy for metastatic colorectal cancer.
AB - Median overall survival of metastatic colorectal cancer patients treated with
first- and second-line combination chemotherapy now extends to more than 20
months in some studies. Chemotherapy alone, particularly when oxaliplatin is
included, may allow potentially curative resection of advanced disease. There is
evidence that the addition of antibodies targeted against vascular endothelial
growth factor or the epidermal growth factor receptor will further improve
prospects for patients with advanced and metastatic disease. However, the optimum
sequencing of chemo- and biological therapies remains to be established, as does
the potential contribution of numerous agents in development.
PMID- 17030639
TI - Genomics and the impact of new technologies on the management of colorectal
cancer.
AB - High-throughput genomic technologies have the potential to have a major impact on
preclinical and clinical drug development and the selection and stratification of
patients in clinical trials. These technologies, which are at varying stages of
commercialization, include array-based comparative genomic hybridization, single
nucleotide polymorphism arrays, and (the most mature example) expression-based
arrays. One of the rate-limiting steps in the routine clinical application of
expression array-based technology is the need for suitable clinical samples. One
of the major challenges moving forward, therefore, relates to the ability to use
formalin-fixed, paraffin-embedded--derived tissue in expression profiling-based
approaches.
PMID- 17030640
TI - The present and future of angiogenesis-directed treatments of colorectal cancer.
AB - The level of angiogenic activity in colorectal tumors has been shown to be a
determinant of survival. Recent trials established that, in both the first- and
second-line treatment of metastatic colorectal cancer, the addition of the
vascular endothelial growth factor (VEGF)-directed antibody bevacizumab to
chemotherapy significantly prolongs survival compared to chemotherapy alone.
Those trials provided proof of principle that inhibition of angiogenesis has the
potential to enhance the effectiveness of treatment of this disease. Oral agents
directed toward VEGF receptor signaling are in advanced development, but none to
date has proven beneficial in phase III trials in advanced colorectal cancer.
Additional trials are needed to determine if improved pharmacological
characteristics of the small molecules can be modified to replicate the activity
of the antibody or if mechanistic differences require a more specific approach.
Since bevacizumab has minimal activity as a single agent, a key question for
future therapeutic development relates to the interaction between antiangiogenic
strategies and cytotoxic therapies. We hypothesize that bevacizumab may
potentiate the efficacy of cytotoxics not solely by alterations of tumor
interstitial pressure but also by promoting sensitivity to proapoptotic signals
consequent upon nutrient and oxygen withdrawal.
PMID- 17030641
TI - Nonsurgical approaches to colorectal cancer.
AB - It is time to challenge the current orthodoxy that frowns upon surgical and
nonsurgical methods of tumor reduction for patients with metastatic colon cancer.
Although the studies conducted with radiofrequency ablation, chemoembolization,
and radiation therapy in patients with metastatic colon cancer have tended to be
small and may have been subject to selection bias, they have produced survival
data that require careful consideration. At the very least, it is clear that
locoregional approaches to debulking tumors are feasible and that their
combination with systemic chemotherapy should be investigated.
PMID- 17030642
TI - Update on capecitabine in colorectal cancer.
AB - In combination chemotherapy for metastatic colorectal cancer, i.v. 5-fluorouracil
(5-FU) can be replaced by oral 5-FU (in the form of capecitabine or another
orally available analogue) without negatively affecting overall toxicity and
without remarkably reducing the efficacy of treatment in terms of response rate
or overall survival. Preclinical evidence of synergy has led to promising early
and successfully completed studies combining capecitabine plus oxaliplatin with
bevacizumab, cetuximab, and epidermal growth factor receptor tyrosine kinase
inhibitors. The use of preoperative capecitabine plus radiation is achieving good
rates of pathological complete response in rectal cancer. While capecitabine is
generally well tolerated, its potential toxicities need careful management and
may require individual dose adaption.
PMID- 17030643
TI - Challenges in the use of epidermal growth factor receptor inhibitors in
colorectal cancer.
AB - Novel targeted agents increase the therapeutic armamentarium in metastatic
colorectal cancer (mCRC). Monoclonal antibodies against the epidermal growth
factor receptor (EGFR) are active against EGFR-expressing mCRC that is refractory
to irinotecan. EGFR monoclonal antibodies also have promise in less advanced
stages of CRC. Cetuximab and panitumumab are clearly active agents. It has been
shown that cetuximab is more active when administered in combination with
irinotecan. Phase II studies also report promising activity when monoclonal
antibodies against the EGFR are combined with classic chemotherapeutic regimens
in the first-line treatment of mCRC. However, the best means of scheduling such
agents and integrating them with each other and with chemotherapy have yet to be
established. The management of toxicity (particularly rash) and finding
appropriate means of selecting patients pose additional challenges. While the
occurrence of rash is associated with greater likelihood of response, EGFR
staining by immunohistochemistry at baseline is not. For reasons that are not yet
clear, the tyrosine kinase inhibitors of EGFR seem less effective than their
monoclonal antibody counterparts in the therapy of mCRC.
PMID- 17030644
TI - Novel therapeutic developments other than EGFR and VEGF inhibition in colorectal
cancer.
AB - Developments that may improve existing cytotoxic therapy for colorectal cancer
(CRC) include alternatives to 5-fluorouracil (5-FU) such as the liposomal
Thymidylate Synthase inhibitor OSI-7904L and the multitargeted antifolate
pemetrexed. Studies have explored means of reformulating irinotecan, modulating
its pharmacokinetics, and enhancing its activity by maximizing DNA damage through
poly(ADP-ribose) polymerase inhibition. Cell cycle inhibitors may offer an
alternative to combination with 5-FU. However, as standard regimens become more
complex, so do the clinical trials needed to develop new agents, and the path to
registration becomes ever more tortuous. It is therefore likely that several
drugs with promise in CRC will not be developed for this indication.
PMID- 17030645
TI - Referral to medical oncology: a crucial step in the treatment of older patients
with stage III colon cancer.
AB - PURPOSE: Adjuvant chemotherapy for stage III colon cancer produces a substantial
survival benefit, but many older patients do not receive chemotherapy. This study
examines factors associated with medical oncology consultation and evaluates the
impact of such consultation on chemotherapy use. PATIENTS AND METHODS: We used
the Surveillance Epidemiology and End Results-Medicare linked database and
identified 7,569 patients, aged 66-99, with stage III colon cancer diagnosed from
1992-1999. Modified Poisson regression was used to assess the relative risk for
seeing a medical oncologist and for receiving chemotherapy as a function of
individual characteristics. RESULTS: 78.08% of patients saw a medical oncologist
within 6 months of diagnosis. Patients who were female, white, married, had low
comorbidity scores, were diagnosed in more recent years, or had four or more
positive lymph nodes were more likely to see a medical oncologist. Patients
seeing a medical oncologist were 10 times more likely to receive chemotherapy
(odds ratio, 9.98; 95% confidence interval, 8.21-12.14), after controlling for
demographic and tumor characteristics. Chemotherapy use increased over time, but
was substantially lower among older, black, and unmarried patients. CONCLUSIONS:
Referral to medical oncology is one of the most important factors associated with
receipt of chemotherapy among older patients with stage III colon cancer.
Comorbidity decreases the likelihood of receiving chemotherapy, but its effect is
the same for those who see a medical oncologist and all patients combined.
Ensuring that high-risk patients are referred to medical oncology is a crucial
step in quality care for patients with colon cancer.
PMID- 17030646
TI - Photodynamic therapy in oncology.
AB - Photodynamic therapy (PDT) is increasingly being recognized as an attractive,
alternative treatment modality for superficial cancer. Treatment consists of two
relatively simple procedures: the administration of a photosensitive drug and
illumination of the tumor to activate the drug. Efficacy is high for small
superficial tumors and, except for temporary skin photosensitization, there are
no long-term side effects if appropriate protocols are followed. Healing occurs
with little or no scarring and the procedure can be repeated without cumulative
toxicity. Considering the efficacy and lack of long-term toxicity of PDT, and the
fact that the first treatment of cancer with PDT was done more than 100 years
ago, one might expect that this treatment had already become an established
therapy. However, PDT is currently offered in only a few selected centers,
although it is slowly gaining acceptance as an alternative to conventional cancer
therapies. Here, we show the developmental steps PDT underwent and summarize the
current clinical applications. The data show that, when properly used, PDT is an
effective alternative treatment option in oncology.
PMID- 17030647
TI - The molecular perspective: alcohol.
PMID- 17030649
TI - Natalizumab and immune cells.
PMID- 17030648
TI - Mediterranean diet, Alzheimer disease, and vascular mediation.
AB - OBJECTIVES: To examine the association between the Mediterranean diet (MeDi) and
Alzheimer disease (AD) in a different AD population and to investigate possible
mediation by vascular pathways. Design, Setting, Patients, and MAIN OUTCOME
MEASURES: A case-control study nested within a community-based cohort in New
York, NY. Adherence to the MeDi (0- to 9-point scale with higher scores
indicating higher adherence) was the main predictor of AD status (194 patients
with AD vs 1790 nondemented subjects) in logistic regression models that were
adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype,
caloric intake, smoking, medical comorbidity index, and body mass index
(calculated as weight in kilograms divided by height in meters squared). We
investigated whether there was attenuation of the association between MeDi and AD
when vascular variables (stroke, diabetes mellitus, hypertension, heart disease,
lipid levels) were simultaneously introduced in the models (which would
constitute evidence of mediation). RESULTS: Higher adherence to the MeDi was
associated with lower risk for AD (odds ratio, 0.76; 95% confidence interval,
0.67-0.87; P<.001). Compared with subjects in the lowest MeDi tertile, subjects
in the middle MeDi tertile had an odds ratio of 0.47 (95% confidence interval,
0.29-0.76) and those at the highest tertile an odds ratio of 0.32 (95% confidence
interval, 0.17-0.59) for AD (P for trend <.001). Introduction of the vascular
variables in the model did not change the magnitude of the association.
CONCLUSIONS: We note once more that higher adherence to the MeDi is associated
with a reduced risk for AD. The association does not seem to be mediated by
vascular comorbidity. This could be the result of either other biological
mechanisms (oxidative or inflammatory) being implicated or measurement error of
the vascular variables.
PMID- 17030650
TI - Acidotoxicity trumps excitotoxicity in ischemic brain.
PMID- 17030651
TI - Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid
and glutamate alterations.
AB - Impairments in certain cognitive functions mediated by the dorsolateral
prefrontal cortex, such as working memory, are core features of schizophrenia.
Convergent findings suggest that these disturbances are associated with
alterations in markers of inhibitory gamma-aminobutyric acid and excitatory
glutamate neurotransmission in the dorsolateral prefrontal cortex. Specifically,
reduced gamma-aminobutyric acid synthesis is present in the subpopulation of
gamma-aminobutyric acid neurons that express the calcium-binding protein
parvalbumin. Despite presynaptic and postsynaptic compensatory responses, the
resulting impaired inhibitory regulation of pyramidal neurons contributes to a
reduction in the synchronized neuronal activity that is required for working
memory function. Several lines of evidence suggest that these changes may be
either secondary to or exacerbated by impaired signaling via the N-methyl-d
aspartate class of glutamate receptors. These findings suggest specific targets
for therapeutic interventions to improve cognitive function in individuals with
schizophrenia.
PMID- 17030653
TI - Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated
patients with multiple sclerosis.
AB - BACKGROUND: Treatment with natalizumab, a monoclonal antibody against the
adhesion molecule very late activation antigen 4, an alpha4beta(1) integrin, was
recently associated with the development of progressive multifocal
leukoencephalopathy, a demyelinating disorder of the central nervous system
caused by JC virus infection. OBJECTIVE: To test the effect of natalizumab
treatment on the CD4(+)/CD8(+) T-cell ratios in cerebrospinal fluid (CSF) and
peripheral blood. DESIGN: Prospective longitudinal study. SETTING: Academic and
private multiple sclerosis centers. PATIENTS: Patients with multiple sclerosis
(MS) treated with natalizumab, untreated patients with MS, patients with other
neurologic diseases, and human immunodeficiency virus-infected patients. MAIN
OUTCOME MEASURES: CD4(+) and CD8(+) T cells were enumerated in CSF and peripheral
blood. The mean fluorescence intensity of unbound alpha4 integrin on peripheral
blood CD4(+) and CD8(+) T cells was analyzed before and after natalizumab
therapy. RESULTS: Natalizumab therapy decreased the CSF CD4(+)/CD8(+) ratio of
patients with MS to levels similar to those of human immunodeficiency virus
infected patients. CD4(+)/CD8(+) ratios in peripheral blood in patients with MS
progressively decreased with the number of natalizumab doses, but they remained
within normal limits. Six months after the cessation of natalizumab therapy, CSF
CD4(+)/CD8(+) ratios normalized. The expression of unbound alpha4 integrin on
peripheral blood T cells decreases with natalizumab therapy and was significantly
lower on CD4(+) vs CD8(+) T cells. CONCLUSIONS: Natalizumab treatment alters the
CSF CD4(+)/CD8(+) ratio. Lower expression of unbound alpha4 integrin on CD4(+) T
cells is one possible mechanism. These results may have implications for the
observation that some natalizumab-treated patients with MS developed progressive
multifocal leukoencephalopathy.
PMID- 17030654
TI - Neuromyelitis optica IgG status in acute partial transverse myelitis.
AB - BACKGROUND: Neuromyelitis optica (NMO) IgG is a specific marker for NMO.
Furthermore, a high proportion of patients with longitudinally extensive
transverse myelitis (characterized by spinal cord lesions extending 3 vertebral
segments or more on magnetic resonance imaging) are seropositive for NMO-IgG and
are considered to have a limited form of NMO. The NMO-IgG status in mild cases of
acute partial transverse myelitis asociated with minimal magnetic resonance
imaging abnormalities (spinal cord lesions <2 vertebral segments on magnetic
resonance imaging) is unknown. OBJECTIVE: To investigate the NMO-IgG status of
patients with acute partial transverse myelitis and a normal cerebral magnetic
resonance image. DESIGN: Observational, retrospective consecutive case series
with longitudinal follow-up. SETTING: Allegheny Multiple Sclerosis Treatment
Center. PATIENTS: Three groups of patients were tested for NMO-IgG. Group 1
consisted of 22 patients with acute partial transverse myelitis, group 2
consisted of 4 patients with definite NMO (by 1999 criteria of Wingerchuk et al),
and group 3 consisted of 6 patients with definite multiple sclerosis. MAIN
OUTCOME MEASURE: NMO-IgG status. A commercially available assay for NMO
antibodies was performed at the Mayo Clinic. Testing was performed during the
convalescent stage of the illness. RESULTS: Of the 22 patients with acute partial
transverse myelitis, only 1 was seropositive for NMO-IgG at presentation. This
patient subsequently developed recurrent episodes of longitudinally extensive
transverse myelitis that are typicaly seen in association with NMO-IgG. Three of
the 4 patients meeting criteria for NMO were seropositive. None of the patients
with multiple sclerosis had NMO-IgG detected. CONCLUSION: NMO-IgG is rarely
encountered in patients with acute partial transverse myelitis, which is in sharp
contrast to the high frequency of this antibody in patients with NMO and
longitudinally extensive transverse myelitis.
PMID- 17030655
TI - Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer
disease: OmegAD study: a randomized double-blind trial.
AB - BACKGROUND: Epidemiologic and animal studies have suggested that dietary fish or
fish oil rich in omega-3 fatty acids, for example, docosahexaenoic acid and
eicosapentaenoic acid, may prevent Alzheimer disease (AD). OBJECTIVE: To
determine effects of dietary omega-3 fatty acid supplementation on cognitive
functions in patients with mild to moderate AD. DESIGN: Randomized, double-blind,
placebo-controlled clinical trial. PARTICIPANTS: Two hundred four patients with
AD (age range [mean +/- SD], 74 +/- 9 years) whose conditions were stable while
receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental
State Examination (MMSE) score of 15 points or more were randomized to daily
intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid (omega
3 fatty acid-treated group) or placebo for 6 months, after which all received
omega-3 fatty acid supplementation for 6 months more. MAIN OUTCOME MEASURES: The
primary outcome was cognition measured with the MMSE and the cognitive portion of
the Alzheimer Disease Assessment Scale. The secondary outcome was global function
as assessed with the Clinical Dementia Rating Scale; safety and tolerability of
omega-3 fatty acid supplementation; and blood pressure determinations. RESULTS:
One hundred seventy-four patients fulfilled the trial. At baseline, mean values
for the Clinical Dementia Rating Scale, MMSE, and cognitive portion of the
Alzheimer Disease Assessment Scale in the 2 randomized groups were similar. At 6
months, the decline in cognitive functions as assessed by the latter 2 scales did
not differ between the groups. However, in a subgroup (n = 32) with very mild
cognitive dysfunction (MMSE >27 points), a significant (P<.05) reduction in MMSE
decline rate was observed in the omega-3 fatty acid-treated group compared with
the placebo group. A similar arrest in decline rate was observed between 6 and 12
months in this placebo subgroup when receiving omega-3 fatty acid
supplementation. The omega-3 fatty acid treatment was safe and well tolerated.
CONCLUSIONS: Administration of omega-3 fatty acid in patients with mild to
moderate AD did not delay the rate of cognitive decline according to the MMSE or
the cognitive portion of the Alzheimer Disease Assessment Scale. However,
positive effects were observed in a small group of patients with very mild AD
(MMSE >27 points).
PMID- 17030656
TI - Intraepidermal nerve fiber densities in chronic inflammatory autoimmune diseases.
AB - BACKGROUND: Some patients with systemic lupus erythematosus have selective loss
of small-diameter nerve fibers, while larger nerve fibers are unaffected.
OBJECTIVE: To determine intraepidermal nerve fiber densities in patients with
different chronic inflammatory autoimmune diseases. DESIGN: Cross-sectional
study. SETTING: Stavanger University Hospital, Stavanger, and Haukeland
University Hospital, Haukeland, Norway. PATIENTS: Sixty patients with systemic
lupus erythematosus (SLE) (mean +/- SD age, 43.2 +/- 13.5 years), 61 patients
with primary Sjogren syndrome (age, 57.1 +/- 14.7 years), and 52 patients with
rheumatoid arthritis (age, 57.4 +/- 12.3 years) were compared with 106 healthy
subjects (age, 49.0 +/- 19.6 years). INTERVENTIONS: Skin biopsy specimens. MAIN
OUTCOME MEASURES: To evaluate small-diameter nerve fiber loss, intraepidermal
nerve fiber densities were measured in skin punch biopsy specimens obtained from
the distal part of the leg. RESULTS: The mean +/- SD densities were 7.5 +/- 3.8
fibers/mm in patients with SLE, 9.2 +/- 3.8 fibers/mm in primary Sjogren
syndrome, and 10.9 +/- 5.4 fibers/mm in rheumatoid arthritis vs 12.4 +/- 4.6
fibers/mm in healthy subjects. Densities were significantly less in patients with
SLE vs patients with rheumatoid arthritis and vs healthy subjects (P<.001 for
both), as well as in patients with primary Sjogren syndrome vs healthy subjects
(P<.001). Eight patients (13%) with SLE, 2 patients (3%) with primary Sjogren
syndrome, and 2 patients (4%) with rheumatoid arthritis had densities below the
lower reference limit of 3.4 fibers/mm, consistent with small-diameter nerve
fiber neuropathy. CONCLUSION: The degree of loss of small-diameter nerve fibers
differs among patients with these chronic inflammatory autoimmune diseases,
likely reflecting differences in pathogenesis and organ affinity of the
individual disease entities.
PMID- 17030657
TI - Calf-head sign in Miyoshi myopathy.
AB - OBJECTIVE: To observe whether patients with Miyoshi-type dysferlinopathy
demonstrate any distinct appearance in the back of the shoulders and upper back
in a specific posture. DESIGN: Case series. SETTING: Neurology outpatient clinic
of a north Indian tertiary care medical institute. PATIENTS: Fifteen patients
from 9 families (10 males and 5 females; age range, 16-42 years) who had Miyoshi
myopathy with onset of calf and shin muscle wasting between the ages of 9 and 28
years and a myopathic pattern at electromyography, moderately high serum creatine
kinase levels, and absence of dysferlin at immunohistochemical staining.
INTERVENTIONS: Patients were asked to raise their arms with shoulders abducted
and elbows flexed to 90 degrees . All were observed from behind for the
morphological change in the bulk of different muscles of the upper back and
shoulders. T1-weighted magnetic resonance imaging of the upper thorax and
shoulder was performed in an oblique sagittal plane to confirm the clinical
findings. MAIN OUTCOME MEASURE: Consistent pattern of muscle enlargement or
wasting seen clinically and at magnetic resonance imaging that produces a
particular diagnostic appearance. RESULTS: A characteristic appearance was
observed on the upper back and shoulders that could be described as calf heads on
a trophy sign. The sign was clearly visible in 6 patients, whereas it was present
in a subtle manner in another 4. Some but not all components of the sign were
visible in the rest of the patients. CONCLUSION: The calf heads on a trophy sign
may be useful in identifying most patients with Miyoshi-type dysferlinopathy.
PMID- 17030658
TI - Composite SISCOM perfusion patterns in right and left temporal seizures.
AB - OBJECTIVE: To compare composite subtraction ictal single-photon emission computed
tomography coregistered to magnetic resonance imaging (also known as SISCOM)
patterns between right and left medial temporal-onset seizures to document
neuroanatomical involvement in perfusion patterns. DESIGN: A retrospective
comparative survey. SETTING: Epilepsy monitoring unit in a tertiary care referral
center. PARTICIPANTS: Subjects with temporal lobe epilepsy (TLE) who underwent
ictal single-photon emission computed tomography studies. MAIN OUTCOME MEASURES:
Comparison of ictal perfusion pattern changes in subjects with right and left
temporal seizures. RESULTS: Composite subtraction ictal single-photon emission
computed tomography coregistered to magnetic resonance images showed similar
regions of hyperperfusion change in the ipsilateral anteromedial temporal-corpus
striatum-insula region in both groups. In the midbrain reticular formation, there
was a significant difference in hyperperfusion between the left and right TLE
groups. In addition, the right, but not the left, TLE group shows contralateral
hypoperfusion of the temporoparietal junction. CONCLUSIONS: While anteromedial
temporal-corpus striatum-insula perfusion patterns are similar, there are
brainstem and hemispheric perfusion pattern differences in right and left TLE
seizures, confirming pathophysiological differences between the groups. These
findings help define neuronal network involvement in TLE seizures, and may
explain the differences in clinical symptoms of right and left TLE seizures.
PMID- 17030660
TI - Measurements of the amygdala and hippocampus in pathologically confirmed
Alzheimer disease and frontotemporal lobar degeneration.
AB - BACKGROUND: Differentiating between Alzheimer disease (AD) and frontotemporal
lobar degeneration (FTLD) can be difficult, particularly in the earliest stages
of the diseases. Patterns of atrophy on magnetic resonance imaging may help
distinguish these diseases and aid diagnosis. OBJECTIVE: To assess the diagnostic
utility of magnetic resonance imaging-derived amygdala and hippocampal volumes
from patients with pathologically proved AD and FTLD. DESIGN: Cross-sectional
volumetric magnetic resonance imaging study of the hippocampus and amygdala.
SETTING: Specialist cognitive disorders clinic. Subjects Thirty-seven subjects,
including 10 patients with pathologically proved AD, 17 patients with
pathologically proved FTLD, and 10 age-matched control subjects. MAIN OUTCOME
MEASURES: Hippocampal and amygdala volumes. RESULTS: Geometric mean amygdala and
hippocampal volumes were, respectively, 15.0% (95% confidence interval [CI], 4.2%
24.5%) and 16.4% (95% CI, 5.9%-25.6%) lower in the AD than in the control group.
In FTLD, the equivalent differences were 43.1% (95% CI, 31.9%-52.6%) in the
amygdala and 36.1% (95% CI, 27.5%-43.7%) in the hippocampus. Volumes were
significantly lower in the FTLD than in the AD group (P<.01 in both regions).
Within the FTLD clinical subgroups, there was evidence of a difference in pattern
of atrophy with greater asymmetry (left smaller than right) in semantic dementia
compared with frontal variant FTLD (P<.001). On average, the left hippocampus was
14% smaller in semantic dementia than in frontal variant FTLD, whereas the right
hippocampus was 37% larger. On average, the left amygdala was 39% smaller in
semantic dementia than in frontal variant FTLD, whereas the right amygdala was
only 1% smaller. CONCLUSIONS: Hippocampal atrophy is not specific to AD or FTLD.
However, severe or asymmetrical amygdala atrophy should suggest FTLD. Atrophy
patterns follow clinical syndromes rather than pathology.
PMID- 17030661
TI - Cognitive impairment and celiac disease.
AB - OBJECTIVE: To characterize the clinical, radiological, and electrophysiological
laboratory profiles and histological features of patients who developed cognitive
impairment temporally associated with celiac disease. DESIGN: Case series.
SETTING: Referral center. PATIENTS: Patients with the onset of progressive
cognitive decline within 2 years of symptomatic onset or with a severe
exacerbation of biopsy-proved adult celiac disease were identified from the Mayo
Clinic medical records from January 1, 1970, to December 31, 2005. Patients were
excluded if an alternate cause of their cognitive impairment was identified.
RESULTS: Thirteen patients (5 women) were identified. The median age at cognitive
impairment onset was 64 years (range, 45-79 years), which coincided with symptom
onset or exacerbation of diarrhea, steatorrhea, and abdominal cramping in 5
patients. Amnesia, acalculia, confusion, and personality changes were the most
common presenting features. The average initial Short Test of Mental Status score
was 28 of a total of 38 (range, 18-34), which was in the moderately impaired
range. The results of neuropsychological testing suggested a trend of a
frontosubcortical pattern of impairment. Ten patients had ataxia, and 4 of them
also had peripheral neuropathy. Magnetic resonance imaging of the head showed
nonspecific T2 hyperintensities, and electroencephalography showed nonspecific
diffuse slowing. Deficiencies in folate, vitamin B(12), vitamin E, or a
combination were identified in 4 patients, yet supplementation did not improve
their neurological symptoms. Three patients improved or stabilized cognitively
with gluten withdrawal. A detailed histological analysis revealed nonspecific
gliosis. CONCLUSIONS: A possible association exists between progressive cognitive
impairment and celiac disease, given the temporal relationship and the relatively
high frequency of ataxia and peripheral neuropathy, more commonly associated with
celiac disease. Given the impact for potential treatment of similar cases,
recognition of this possible association and additional studies are warranted.
PMID- 17030659
TI - Visual hallucinations in posterior cortical atrophy.
AB - BACKGROUND: Visual hallucinations have been reported to occur in up to 25% of
patients who meet the criteria for posterior cortical atrophy (PCA). It is not
known, however, whether patients who meet the criteria for PCA and have
hallucinations are different from those who meet the criteria and do not have
hallucinations. OBJECTIVE: To compare the clinical and imaging features of
patients with PCA with and without well-formed visual hallucinations. DESIGN:
Case-control study. SETTING: Tertiary care medical center. PATIENTS: Fifty-nine
patients fulfilling the criteria for PCA were retrospectively identified and
divided into 2 groups based on the presence (n = 13) or absence (n = 46) of
visual hallucinations. MAIN OUTCOME MEASURES: Statistically significant clinical
differences and imaging differences using voxel-based morphometry between the 2
groups. RESULTS: In patients with PCA and hallucinations, parkinsonism and rapid
eye movement sleep behavior disorder occurred more frequently, as did myoclonic
jerks (P<.001 for both). Voxel-based morphometry showed greater atrophy in a
network of structures, including the primary visual cortex, lentiform nuclei,
thalamus, basal forebrain, and midbrain, in patients with hallucinations.
CONCLUSIONS: Hallucinations in patients with PCA are associated with
parkinsonism, rapid eye movement sleep behavior disorder, and myoclonic jerks.
The voxel-based morphometry results suggest that hallucinations in PCA cannot be
exclusively attributed to atrophy of the posterior association cortices and may
involve a circuit of thalamocortical connections.
PMID- 17030662
TI - The progression of cognition, psychiatric symptoms, and functional abilities in
dementia with Lewy bodies and Alzheimer disease.
AB - BACKGROUND: Although dementia with Lewy bodies (DLB) may be one of most common
forms of dementia, relatively little is known about its cognitive and functional
course. OBJECTIVE: To compare change over time in general cognitive status,
memory test performance, psychiatric symptoms, neurological signs, and functional
abilities in patients with probable DLB and probable Alzheimer disease (AD).
DESIGN: Twenty-eight patients who met diagnostic criteria for DLB were recruited
into the study from 3 sites. Patients with AD (n = 55) were selected from a
larger cohort and matched 2 to 1 to the patients with DLB on age and baseline
global cognitive status. Patients were followed up at 6-month intervals for an
average of 6.2 visits and assessed at each visit with tests of global cognitive
functioning and verbal learning and memory and measures of psychiatric,
neurological, and functional status. RESULTS: At the baseline evaluation,
patients with DLB performed more poorly on a measure of constructional praxis and
all measures of functional status. They also had more severe psychiatric symptoms
and neurological signs than the AD group. Despite these initial differences,
generalized estimating equations applied to regression analyses with repeated
measures determined that the only difference between the 2 groups in change in
cognitive test performance was on a measure of recognition memory; patients with
AD declined, while patients with DLB remained relatively stable. Patients with
DLB had relatively stable behavioral symptoms and visual illusions, whereas
patients with AD had a significant increase in these symptoms over time.
Neurological and functional changes over time were similar in the 2 groups.
CONCLUSIONS: Both baseline and longitudinal differences between patients with DLB
and patients with AD were noted; these have implications for clinical diagnosis
and treatment.
PMID- 17030663
TI - Tauopathy-like abnormalities and neurologic deficits in mice immunized with
neuronal tau protein.
AB - BACKGROUND: A possible role of autoimmunity in Alzheimer disease pathogenesis has
recently attracted increasing attention. Vaccination with amyloid-beta peptide
was reported to cause marked reduction in amyloid deposition, but it also induced
encephalitis. Not much is known regarding neurofibrillary tangle-related
autoimmune effects. OBJECTIVE: To use the main component of tangles-microtubule
associated tau protein-to test the feasibility of active induction of a
neuroautoimmune disorder in mice. DESIGN: Prospective, randomized controlled
animal study. SETTING: University medical center research laboratory. Subjects
Female C57BL/6 mice. INTERVENTIONS: Inoculation with recombinant human tau
protein emulsified in complete Freund adjuvant and with pertussis toxin. MAIN
OUTCOME MEASURES: Clinical, immunologic, pathologic, and behavioral evaluations
were performed. RESULTS: Vaccination with tau protein induced histopathologic
features of Alzheimer disease and tauopathies, indicated by the presence of
neurofibrillary tangle-like structures, axonal damage, and gliosis. Also,
mononuclear infiltrates without demyelination in the central nervous system,
accompanied by neurologic deficits (such as a limp tail and limb paralysis), were
observed. Anti-tau antibodies were detected in the serum of tau-immunized mice.
CONCLUSIONS: These results provide a link between tau autoimmunity and tauopathy
like abnormalities and indicate potential dangers of using tau for immunotherapy.
This experimental autoimmune tauopathy-like model is due to a pathogenic immune
response against an intraneuronal antigen and is not related to myelin antigens.
PMID- 17030664
TI - Magnetic resonance neurography in extraspinal sciatica.
AB - BACKGROUND: Sciatica without evidence of lumbosacral root compression is often
attributed to piriformis syndrome. However, specific diagnostic tools have not
been available to demonstrate sciatic nerve entrapment by the piriformis muscle.
OBJECTIVE: To evaluate the use of magnetic resonance (MR) neurography in
identifying abnormalities of the sciatic nerve in patients with unexplained
sciatica. DESIGN: Case series from a retrospective medical record review.
PATIENTS: Fourteen patients with sciatic distribution pain and normal results on
MR imaging for lumbosacral radiculopathy were referred for MR neurography of the
lumbosacral plexus and sciatic nerves. RESULTS: In 12 patients, MR neurography
demonstrated increased fluid-attenuated inversion recovery signal in the
ipsilateral sciatic nerve. In most patients, this abnormal signal was seen at the
sciatic notch, at or just inferior to the level of the piriformis muscle. To
date, 4 patients have undergone surgical decompression, with excellent relief of
symptoms in 3 of them. CONCLUSION: Magnetic resonance neurography often
identifies an abnormal increased signal in the proximal sciatic nerve in patients
with extraspinal sciatica and allows more accurate diagnosis of sciatic nerve
entrapment in suspected cases.
PMID- 17030665
TI - Reversible posterior leukoencephalopathy syndrome after bevacizumab/FOLFIRI
regimen for metastatic colon cancer.
AB - OBJECTIVE: To describe a patient with reversible posterior leukoencephalopathy
syndrome following the administration of bevacizumab (Avastin), a monoclonal
antibody against vascular endothelial growth factor. DESIGN: Case
report/literature review. SETTING: University hospital. PATIENT: A 52-year-old
man receiving chemotherapy for stage IV rectal carcinoma. RESULTS: Clinical and
radiographic evidence consistent with reversible posterior leukoencephalopathy
syndrome was found following the administration of irinotecan hydrochloride,
leucovorin calcium, and fluorouracil (FOLFIRI) regimen chemotherapy and
bevacizumab. CONCLUSIONS: Reversible posterior leukoencephalopathy syndrome
following treatment with angiogenesis modulators can occur. In addition to
raising clinical suspicion in appropriate patients, this report may yield clues
to the pathophysiologic underpinnings of reversible posterior leukoencephalopathy
syndrome.
PMID- 17030666
TI - Betamethasone and improvement of neurological symptoms in ataxia-telangiectasia.
AB - BACKGROUND: To our knowledge, there have been no reports on the control of
central nervous system symptoms in patients with ataxia-telangiectasia.
OBJECTIVE: To preliminarily determine the effectiveness of corticosteroid therapy
on the central nervous system symptoms of a child with ataxia-telangiectasia in
whom neurological signs improved when, occasionally, he was given betamethasone
to treat asthmatic bronchitis attacks. DESIGN: Case report. SETTING: Tertiary
care hospital. Patient A 3-year-old boy with the classic hallmarks and a proved
molecular diagnosis of ataxia-telangiectasia. INTERVENTIONS: We used
betamethasone, 0.1 mg/kg per 24 hours, divided every 12 hours, for 4 weeks to
preliminarily determine its effectiveness on the child's central nervous system
symptoms and its safety. Methylprednisolone, 2 mg/kg per 24 hours, divided every
12 hours, was then given in an attempt to perform a long-term treatment. RESULTS:
There were improvements in the child's neurological symptoms 2 or 3 days after
the beginning of the drug treatment. After 2 weeks of treatment, the improvement
was dramatic: the disturbance of stance and gait was clearly reduced, and the
control of the head and neck had increased, as had control of skilled movements.
At 4 weeks of treatment, adverse effects mainly included increased appetite and
body weight and moon face. No beneficial effect was obtained when, after 4 weeks,
betamethasone was replaced with methylprednisolone. Six months later, without
therapy, the child continued to experience severe signs of central nervous system
impairment. CONCLUSION: Controlled studies to better understand the most
appropriate drug and therapeutic schedule are required.
PMID- 17030667
TI - T313M PINK1 mutation in an extended highly consanguineous Saudi family with early
onset Parkinson disease.
AB - BACKGROUND: To date, 5 well-confirmed genes for Parkinson disease (PD) have been
identified, including 3 autosomal recessive genes: PTEN-induced putative kinase 1
(PINK1), parkin, and DJ-1. Almost nothing is known about the genetics of PD in
Saudi Arabia; however, consanguineous families, not infrequent in this
population, could be important in the evaluation of known PD genes and the search
for new PD factors in the future. OBJECTIVE: To investigate known recessive PD
genes in 5 consanguineous Saudi families with PD. DESIGN: The entire open frame
as well as the untranslated region and all 5' and 3' intron-exon boundaries of
the PINK1, parkin, and DJ-1 genes were sequenced in 5 probands in Saudi families.
RESULTS: Four of 5 probands tested negative for PINK1, parkin, and DJ-1
mutations. However, in a large Saudi family with PD with at least 3
consanguineous marriages between first cousins, we detected a threonine to
methionine substitution at codon 313 (T313M) PINK1 mutation that affected the
kinase domain. Manifestations of the disease in this family included early onset
(age, 28-38 years), tremulous movement, slow progression, diurnal fluctuations,
bradykinesia, good response to levodopa therapy, and only mild dyskinesias. A
neurologist blinded to genetic status clinically evaluated 15 family members, all
older than 20 years, and diagnosed PD only in individuals who were later found to
be homozygous for the T313M mutation. None of the 13 heterozygotes demonstrated
any sign of PD. CONCLUSION: A homozygous T313M mutation is responsible for PD in
this large Saudi family. However, the heterozygous T313M mutation does not act as
a PD susceptibility factor, which is in contrast to several reports of mutations
affecting only 1 PINK1 allele discovered in sporadic PD.
PMID- 17030668
TI - Cluster breathing associated with bihemispheric infarction and sparing of the
brainstem.
AB - OBJECTIVE: To report cluster breathing pattern associated with a nonbrainstem
lesion. DESIGN: Case report. SETTING: Neurointensive care unit, St Mary's
Hospital, Rochester, Minn. PATIENT: A patient with subarachnoid hemorrhage
developed severe, diffuse, distal bilateral middle cerebral artery vasospasm with
resultant cortical laminar necrosis and transient cluster breathing. Intervention
Magnetic resonance imaging revealed bihemispheric lesions but no brainstem
lesion. CONCLUSION: Cluster breathing may occur with nonbrainstem lesions.
PMID- 17030669
TI - POMGnT1 mutations in congenital muscular dystrophy: genotype-phenotype
correlation and expanded clinical spectrum.
AB - BACKGROUND: Muscle-eye-brain disease is a congenital muscular dystrophy with eye
and brain involvement due to POMGnT1 mutations. OBJECTIVE: To describe the
clinical and molecular features of 3 Italian patients with POMGnT1 mutations.
DESIGN: Case reports. PATIENTS: One patient had muscle and brain abnormalities
without eye involvement. Two patients had a classic muscle-eye-brain disease
phenotype with different levels of clinical severity. RESULTS: Brain magnetic
resonance imaging showed cortical malformation and posterior fossa involvement.
Immunofluorescence for glycosylated alpha-dystroglycan performed on muscle biopsy
specimens demonstrated an absent signal in 1 patient and reduced staining in 2
patients. Molecular analysis identified 5 mutations, 2 of which are novel.
CONCLUSION: This article adds to what is known about the genotype-phenotype
correlation and expands our awareness of the clinical spectrum associated with
POMGnT1 mutations.
PMID- 17030670
TI - Bradycardia after coiling of giant vertebral aneurysm.
PMID- 17030671
TI - Bilateral pontine infarction secondary to basilar trunk saccular aneurysm.
PMID- 17030672
TI - Vein of galen aneurysmal malformation.
PMID- 17030673
TI - Diabetic neuropathies.
PMID- 17030674
TI - Nonstroke treatment.
PMID- 17030675
TI - Potassium-retaining diuretics and incident Alzheimer disease.
PMID- 17030676
TI - Benign tremulous parkinsonism?
PMID- 17030677
TI - Blood pressure in mutant rats lacking the 5-hydroxytryptamine transporter.
PMID- 17030678
TI - Anabolic deficiency in men with chronic heart failure: prevalence and detrimental
impact on survival.
AB - BACKGROUND: The age-related decline of circulating anabolic hormones in men is
associated with increased morbidity and mortality. We studied the prevalence and
prognostic consequences of deficiencies in circulating total testosterone (TT)
and free testosterone, dehydroepiandrosterone sulfate (DHEAS), and insulin-like
growth factor-1 (IGF-1) in men with chronic heart failure (CHF). METHODS AND
RESULTS: Serum levels of TT, DHEAS, and IGF-1 were measured with immunoassays in
208 men with CHF (median age 63 years; median left ventricular ejection fraction
33%; New York Heart Association class I/II/III/IV, 19/102/70/17) and in 366
healthy men. Serum levels of free testosterone were estimated (eFT) from levels
of TT and sex hormone binding globulin. Deficiencies in DHEAS, TT, eFT, and IGF
1, defined as serum levels at or below the 10th percentile of healthy peers, were
seen across all age categories in men with CHF. DHEAS, TT, and eFT were inversely
related to New York Heart Association class irrespective of cause (all P<0.01).
DHEAS correlated positively with left ventricular ejection fraction and inversely
with N-terminal pro-brain natriuretic peptide (both P<0.01). Circulating TT, eFT,
DHEAS, and IGF-1 levels were prognostic markers in multivariable models when
adjusted for established prognostic factors (all P<0.05). Men with CHF and normal
levels of all anabolic hormones had the best 3-year survival rate (83%, 95% CI
67% to 98%) compared with those with deficiencies in 1 (74% survival rate, 95% CI
65% to 84%), 2 (55% survival rate, 95% CI 45% to 66%), or all 3 (27% survival
rate, 95% CI 5% to 49%) anabolic endocrine axes (P<0.0001). CONCLUSIONS: In male
CHF patients, anabolic hormone depletion is common, and a deficiency of each
anabolic hormone is an independent marker of poor prognosis. Deficiency of >1
anabolic hormone identifies groups with a higher mortality.
PMID- 17030679
TI - Absence of malonyl coenzyme A decarboxylase in mice increases cardiac glucose
oxidation and protects the heart from ischemic injury.
AB - BACKGROUND: Acute pharmacological inhibition of cardiac malonyl coenzyme A
decarboxylase (MCD) protects the heart from ischemic damage by inhibiting fatty
acid oxidation and stimulating glucose oxidation. However, it is unknown whether
chronic inhibition of MCD results in altered cardiac function, energy metabolism,
or ischemic cardioprotection. METHODS AND RESULTS: Mcd-deficient mice were
produced and assessed for in vivo cardiac function as well as ex vivo cardiac
function, energy metabolism, and ischemic tolerance. In vivo and ex vivo cardiac
function was similar in wild-type and mcd-/- mice. Ex vivo working hearts from
mcd-/- and wild-type mice displayed no significant differences in rates of fatty
acid oxidation, glucose oxidation, or glycolysis. However, cardiac deletion of
mcd resulted in an increased expression of genes regulating fatty acid
utilization that may compensate for the loss of MCD protein and likely
contributes to the absence of changes in energy metabolism in the aerobic heart.
Despite the lack of changes in fatty acid utilization, hearts from mcd-/- mice
displayed a marked preference for glucose utilization after ischemia, which
correlated with a significant cardioprotection of ischemic hearts from mcd-/-
mice compared with wild-type mice. CONCLUSIONS: Deletion of MCD markedly
increases glucose oxidation and improves functional recovery of the heart after
ischemia. As a result, chronic pharmacological inhibition of MCD may be a viable
approach to treat myocardial ischemia.
PMID- 17030680
TI - Results from the Loire-Ardeche-Drome-Isere-Puy-de-Dome (LADIP) trial on atrial
flutter, a multicentric prospective randomized study comparing amiodarone and
radiofrequency ablation after the first episode of symptomatic atrial flutter.
AB - BACKGROUND: There is no published randomized study comparing amiodarone therapy
and radiofrequency catheter ablation (RFA) after only 1 episode of symptomatic
atrial flutter (AFL). The aim of the Loire-Ardeche-Drome-Isere-Puy-de-Dome
(LADIP) Trial of Atrial Flutter was 2-fold: (1) to prospectively compare first
line RFA (group I) versus cardioversion and amiodarone therapy (group II) after
only 1 AFL episode; and (2) to determine the impact of both treatments on the
long-term risk of subsequent atrial fibrillation (AF). METHODS AND RESULTS: From
October 2002 to February 2006, 104 patients (aged 78+/-5 years; 20 women) with
AFL were included, with 52 patients in group I and 52 patients in group II. The
cumulative risk of AFL or AF was interpreted with the use of Kaplan-Meier curves
and compared by the log-rank test. Clinical presentation, echocardiographic data,
and follow-up were as follows: age (78.5+/-5 versus 78+/-5 years), history of AF
(27% versus 21.6%); structural heart disease (58% versus 65%), left ventricular
ejection fraction (56+/-14% versus 54.5+/-14%), left atrial size (43+/-7 versus
43+/-6 mm), mean follow-up (13+/-6 versus 13+/-6 months; P=NS), recurrence of AFL
(3.8% versus 29.5%; P<0.0001), and occurrence of significant AF beyond 10 minutes
(25% versus 18%; P=0.3). Five complications (10%) were noted in group II (sick
sinus syndrome in 2, hyperthyroidism in 1, and hypothyroidism in 2) and none in
group I (0%) (P=0.03). CONCLUSIONS: RFA should be considered a first-line therapy
even after the first episode of symptomatic AFL. There is a better long-term
success rate, the same risk of subsequent AF, and fewer secondary effects.
PMID- 17030681
TI - Gene transfer of a synthetic pacemaker channel into the heart: a novel strategy
for biological pacing.
AB - BACKGROUND: One key element of natural pacemakers is the pacemaker current
encoded by the hyperpolarization-activated nucleotide-gated channel (HCN) gene
family. Although HCN gene transfer has been used to engineer biological
pacemakers, this strategy may be confounded by unpredictable consequences of
heteromultimerization with endogenous HCN family members and limited flexibility
with regard to frequency tuning of the engineered pacemaker. METHODS AND RESULTS:
To circumvent these limitations, we converted a depolarization-activated
potassium-selective channel, Kv1.4, into a hyperpolarization-activated
nonselective channel by site-directed mutagenesis (R447N, L448A, and R453I in S4
and G528S in the pore). Gene transfer into ventricular myocardium demonstrated
the ability of this construct to induce pacemaker activity with spontaneous
action potential oscillations in adult ventricular myocytes and idioventricular
rhythms by in vivo electrocardiography. CONCLUSIONS: Given the sparse expression
of Kv1 family channels in the human ventricle, gene transfer of a synthetic
pacemaker channel based on the Kv1 family has novel therapeutic potential as a
biological alternative to electronic pacemakers.
PMID- 17030682
TI - Endotoxin-induced cardiomyopathy and systemic inflammation in mice is prevented
by aldose reductase inhibition.
AB - BACKGROUND: Sepsis is a systemic inflammatory response syndrome characterized by
excessive production of inflammatory cytokines and cardiovascular collapse.
Postreceptor signaling events that lead to stress responses and cytokine
production are sensitive to redox changes and products of lipid peroxidation.
METHODS AND RESULTS: We tested the hypothesis that inflammatory signaling and
cytokine generation during sepsis depend on the activity of the enzyme aldose
reductase, which catalyzes the reduction of lipid peroxidation-derived aldehydes
and their glutathione conjugates. The results of the present study show that
pharmacological inhibition of aldose reductase by sorbinil or knockdown of the
enzyme by small interfering RNA prevents the activation of nuclear factor-kappaB
and the release of tumor necrosis factor-alpha from lipopolysaccharide-stimulated
RAW264.7 or H9c2 cells. Increases in serum and cardiac cytokines in response to
lipopolysaccharide challenge were suppressed by inhibition of aldose reductase.
Treatment with sorbinil blunted the activation of protein kinase C, c-Jun NH2
terminal kinase, and p38, as well as phosphorylation of interleukin receptor
associated kinase, IkappaB-alpha, IkappaB kinase complex-alpha/beta, and
phospholipase-gamma1 and -beta1. These changes were associated with decreased
myocardial nuclear factor-kappaB and activating protein-1 activity, prostaglandin
E2 production, induction of cyclooxygenase 2, and inducible nitric oxide
synthase. Sorbinil treatment also induced functional recovery in myocardial
fractional shortening in vivo and preserved contractile function of isolated
perfused hearts. Inhibition of aldose reductase increased survival in mice
injected with lethal doses of lipopolysaccharide. CONCLUSIONS: The present
demonstration that aldose reductase mediates endotoxin-induced inflammation and
cardiomyopathy suggests that inhibition of this enzyme may be useful to attenuate
maladaptive host responses and to treat acute cardiovascular dysfunction
associated with endotoxic shock.
PMID- 17030683
TI - Low birth weight, a risk factor for cardiovascular diseases in later life, is
already associated with elevated fetal glycosylated hemoglobin at birth.
AB - BACKGROUND: It remains unclear whether the association between low birth weight
and insulin resistance in adulthood has its origin in utero or whether it
develops later in life depending on predisposition and exogenous factors. METHODS
AND RESULTS: Total glycosylated hemoglobin (TGH) was quantified at delivery in
1295 mother/child pairs serving as a surrogate of maternal and fetal glycemia.
Multivariable regression analysis considering gestational age at delivery, the
child's sex, maternal body mass index, and smoking during pregnancy revealed that
an increase in TGH by 1% in the child was significantly associated with a mean
birth weight reduction of 135 g (P<0.0001), whereas the same increase in the
mother was associated with a mean birth weight increase of 88 g (P<0.0001). The
ratio of fetal/maternal TGH suggests that lighter newborns have a higher
percentage of TGH than would be expected from maternal TGH. CONCLUSIONS: The
study demonstrates for the first time in a large population that there is an
inverse association between TGH of a newborn and its birth weight. This might be
due to increased insulin resistance in newborns with lower birth weight. Our data
suggest that the pathophysiological mechanisms linking prenatal growth and
postnatal sensitivity to insulin are present as early as before birth.
PMID- 17030684
TI - Age- and training-dependent development of arrhythmogenic right ventricular
cardiomyopathy in heterozygous plakoglobin-deficient mice.
AB - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an
inherited disorder that causes sudden death and right ventricular heart failure
in the young. Clinical data suggest that competitive sports may provoke ARVC in
susceptible persons. Genetically, loss-of-function mutations in desmosomal
proteins (plakophilin, desmoplakin, or plakoglobin) have been associated with
ARVC. To test the hypothesis that reduced desmosomal protein expression causes
ARVC, we studied the cardiac effects of heterozygous plakoglobin deficiency in
mice. METHODS AND RESULTS: Ten-month-old heterozygous plakoglobin-deficient mice
(plakoglobin+/-) had increased right ventricular volume, reduced right
ventricular function, and spontaneous ventricular ectopy (all P<0.05). Left
ventricular size and function were not altered. Isolated, perfused plakoglobin+/-
hearts had spontaneous ventricular tachycardia of right ventricular origin and
prolonged right ventricular conduction times compared with wild-type hearts.
Endurance training accelerated the development of right ventricular dysfunction
and arrhythmias in plakoglobin+/- mice. Histology and electron microscopy did not
identify right ventricular abnormalities in affected animals. CONCLUSIONS:
Heterozygous plakoglobin deficiency provokes ARVC. Manifestation of the phenotype
is accelerated by endurance training. This suggests a functional role for
plakoglobin and training in the development of ARVC.
PMID- 17030686
TI - Indications for renal arteriography at the time of coronary arteriography: a
science advisory from the American Heart Association Committee on Diagnostic and
Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the
Councils on Cardiovascular Radiology and Intervention and on Kidney in
Cardiovascular Disease.
AB - Atherosclerotic renal artery stenosis is commonly present in patients with
clinically manifest atherosclerosis in other vascular beds and is independently
associated with increased cardiovascular morbidity and mortality. Screening tests
such as renal angiography should be selectively applied to patients at high risk
for renal artery stenosis who are potential candidates for revascularization.
This multispecialty consensus document describes the rationale for patient
selection for screening renal angiography at the time of cardiac catheterization.
PMID- 17030685
TI - Pirfenidone prevents the development of a vulnerable substrate for atrial
fibrillation in a canine model of heart failure.
AB - BACKGROUND: Atrial fibrosis is an important substrate in atrial fibrillation
(AF), particularly in the setting of structural heart disease. In a canine model,
congestive heart failure (CHF) produces significant atrial fibrosis and the
substrate for sustained AF. This atrial remodeling is a potential therapeutic
target. The objective of the present study is to evaluate the effects of the
antifibrotic drug pirfenidone (PFD) on arrhythmogenic atrial remodeling in a
canine CHF model. METHODS AND RESULTS: We studied 15 canines, divided equally
into 3 groups: control, CHF canines not treated with PFD, and CHF canines treated
with PFD. CHF was induced by ventricular tachypacing (220 bpm for 3 weeks), and
oral PFD was administered for the 3-week pacing period. We performed
electrophysiology and AF vulnerability studies, atrial fibrosis measurements, and
atrial cytokine expression studies. Only canines in the untreated CHF group
developed sustained AF (>30 minutes, 4 of 5 canines; P<0.05). Treatment of CHF
canines with PFD resulted in an attenuation of arrhythmogenic left atrial
remodeling, with a significant reduction in left atrial conduction heterogeneity
index (median [25% to 75% interquartile range] 4.96 [3.53 to 5.64] versus 2.52
[2.11 to 2.82], P<0.01; pacing cycle length 300 ms), left atrial fibrosis (16.0%
[13.0% to 17.5%] versus 8.7% [5.7% to 10.6%], P<0.01), and AF duration (1800
[1020 to 1800] seconds versus 6 [5 to 22] seconds, P<0.01). Immunoblotting
studies demonstrated the drug's effects on multiple cytokines, including a
reduction in transforming growth factor-beta1 expression. CONCLUSIONS: Treatment
of CHF canines with PFD results in significantly reduced arrhythmogenic atrial
remodeling and AF vulnerability. Pharmacological therapy targeted at the fibrotic
substrate itself may play an important role in the management of AF.
PMID- 17030687
TI - Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by
short-term administration of an antisense inhibitor of apolipoprotein B.
AB - BACKGROUND: Apolipoprotein B (apoB) is an important structural component of low
density lipoprotein cholesterol (LDL-C) and plays a key role in LDL-C transport
and removal. Reduction in apoB synthesis is expected to reduce circulating LDL-C,
a proven risk factor of cardiovascular disease. In the present study, we describe
the outcome of the first-in-humans study on the safety and efficacy of an
antisense oligonucleotide inhibitor of apoB. METHODS AND RESULTS: This study was
a double-blind, randomized, placebo-controlled, dose-escalation investigation
conducted at a single site in 36 volunteers with mild dyslipidemia. The study
utilized an initial single dose of 50 to 400 mg of ISIS 301012, a 20-mer
oligonucleotide, followed by a 4-week multiple-dosing regimen with the same
assigned dose. Safety was assessed by the incidence, severity, and relationship
of adverse events to dose. Efficacy was determined by changes in serum apoB and
LDL-C relative to baseline and placebo. The most common adverse event was
erythema at the injection site (21 of 29 subjects). ApoB was reduced by a maximum
of 50% (P=0.002) from baseline in the 200-mg cohort. This decrease in apoB
coincided with a maximum 35% reduction of LDL-C (P=0.001). LDL-C and apoB
remained significantly below baseline (P<0.05) up to 3 months after the last
dose. CONCLUSIONS: Administration of an antisense oligonucleotide to human apoB
resulted in a significant, prolonged, and dose-dependent reduction in apoB and
LDL-C. Although injection-site reactions were common, adherence to protocol was
unaffected.
PMID- 17030688
TI - Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary
observational study.
AB - BACKGROUND: Phosphodiesterase-5 inhibitors produce a significant decrease in
pulmonary vascular resistance in patients with idiopathic pulmonary arterial
hypertension. We studied the effects of tadalafil, a phosphodiesterase-5
inhibitor, on short-term hemodynamics, tolerability, and efficacy over a 12-week
period in patients of Eisenmenger syndrome having a pulmonary vascular pathology
similar to idiopathic pulmonary arterial hypertension. METHODS AND RESULTS:
Sixteen symptomatic Eisenmenger syndrome patients (mean age, 25+/-8.9 years) were
assessed hemodynamically at baseline and 90 minutes after a single dose of
tadalafil (1 mg/kg body weight up to a maximum of 40 mg). The same dose was then
continued daily for 12 weeks, and the patients were restudied. There was a
significant decrease in mean pulmonary vascular resistance immediately (24.75+/
8.49 to 19.22+/-8.23 Woods units; P<0.005) and at 12 weeks (19.22+/-8.23 to
17.02+/-6.19 Woods units; P=0.03 versus 90 minutes). Thirteen of 16 patients
(81.25%) showed a > or = 20% decrease in pulmonary vascular resistance and were
defined as responders. The mean systemic oxygen saturation improved significantly
both immediately (84.34+/-5.47% to 87.39+/-4.34%; P<0.005) and at 12 weeks
(87.39+/-4.34% to 89.16+/-3.8%; P<0.02 versus 90 minutes) without a significant
change in systemic vascular resistance. None of the patients had a fall in
systemic arterial pressure, worsening of systemic oxygen saturation, or any
adverse reactions to the drug. The mean World Health Organization functional
class improved from 2.31+/-0.47 to 1.25+/-0.44 (P<0.0001), and the 6-minute walk
distance improved from 344.56+/-119.06 to 387.56+/-117.18 m (P<0.001).
CONCLUSIONS: Preliminary evaluation of tadalafil has shown efficacy and safety in
selected patients with Eisenmenger syndrome, warranting further investigation in
this subgroup of patients.
PMID- 17030689
TI - Induction of macrophage chemotaxis by aortic extracts of the mgR Marfan mouse
model and a GxxPG-containing fibrillin-1 fragment.
AB - BACKGROUND: The primary cause of early death in untreated Marfan syndrome (MFS)
patients is aortic dilatation and dissection. METHODS AND RESULTS: We
investigated whether ascending aortic samples from the fibrillin-1
underexpressing mgR mouse model for MFS or a recombinant fibrillin-1 fragment
containing an elastin-binding protein (EBP) recognition sequence can act as
chemotactic stimuli for macrophages. Both the aortic extracts from the mgR/mgR
mice and the fibrillin-1 fragment significantly increased macrophage chemotaxis
compared with extracts from wild-type mice or buffer controls. The chemotactic
response was significantly diminished by pretreatment of macrophages with lactose
or with the elastin-derived peptide VGVAPG and by pretreatment of samples with a
monoclonal antibody directed against an EBP recognition sequence. Mutation of the
EBP recognition sequence in the fibrillin-1 fragment also abolished the
chemotactic response. These results indicate the involvement of EBP in mediating
the effects. Additionally, investigation of macrophages in aortic specimens of
MFS patients demonstrated macrophage infiltration in the tunica media.
CONCLUSIONS: Our findings demonstrate that aortic extracts from mgR/mgR mice can
stimulate macrophage chemotaxis by interaction with EBP and show that a fibrillin
1 fragment possesses chemotactic stimulatory activity similar to that of elastin
degradation peptides. They provide a plausible molecular mechanism for the
inflammatory infiltrates observed in the mgR mouse model and suggest that
inflammation may represent a component of the complex pathogenesis of MFS.
PMID- 17030690
TI - Elevated matrix metalloproteinase-9 associated with stroke or cardiovascular
death in patients with carotid stenosis.
AB - BACKGROUND: Matrix metalloproteinase-9 could exhibit an important role in the
destabilization of atherosclerotic carotid plaques. We hypothesized that in
patients with carotid stenosis, elevated levels of plasma matrix
metalloproteinase-9 are associated with ipsilateral stroke or cardiovascular
death. METHODS AND RESULTS: We followed up 207 patients with > or = 50% carotid
stenosis initially for a mean of 4.4 years, during which time 53 patients
developed ipsilateral stroke or died of cardiovascular causes. The cumulative
incidence of ipsilateral stroke or cardiovascular death was higher in those with
matrix metalloproteinase-9 above versus below the median of 41.9 ng/mL (log-rank
P=0.002). Matrix metalloproteinase-9 above versus below the median had a hazard
ratio for ipsilateral stroke or cardiovascular death of 1.9 (95% confidence
interval [CI], 1.1 to 3.5); during extended follow-up, this remained significant
until 10 years. The absolute risk of ipsilateral stroke or cardiovascular death
at 4.4 years was 34% and 17% in those with matrix metalloproteinase-9 above and
below the median, respectively. Elevated matrix metalloproteinase-9 and an
echolucent plaque on B-mode ultrasound versus a low matrix metalloproteinase-9
and an echorich plaque had a hazard ratio for ipsilateral stroke or
cardiovascular death of 4.4 (95% CI, 1.8 to 11.1) and for ipsilateral stroke of
3.3 (95% CI, 1.1 to 9.7). CONCLUSIONS: Elevated levels of matrix
metalloproteinase-9 in patients with > or = 50% carotid stenosis were associated
with a 2-fold risk of ipsilateral stroke or cardiovascular death. Combining
elevated matrix metalloproteinase-9 and plaque echolucency was associated with a
4-fold risk for ipsilateral stroke or cardiovascular death and a 3-fold risk for
ipsilateral stroke.
PMID- 17030691
TI - Cardiology patient page. The metabolic syndrome.
PMID- 17030692
TI - Images in cardiovascular medicine. Cough cardiopulmonary resuscitation revisited.
PMID- 17030693
TI - Images in cardiovascular medicine. Case of anomalous right superior vena cava.
PMID- 17030694
TI - Images in cardiovascular medicine. Hiccups and dysphonic metallic voice: a unique
presentation of Twiddler syndrome.
PMID- 17030695
TI - Letter by Nieminen et al regarding article, "Differential impact of blood
pressure-lowering drugs on central aortic pressure and clinical outcomes:
principal results of the Conduit Artery Function Evaluation (CAFE) study".
PMID- 17030696
TI - Letter by Dart et al regarding article, "Differential impact of blood pressure
lowering drugs on central aortic pressure and clinical outcomes: principal
results of the Conduit Artery Function Evaluation (CAFE) study".
PMID- 17030697
TI - Letter by Cameron et al regarding article, "Differential impact of blood pressure
lowering drugs on central aortic pressure and clinical outcomes: principal
results of the Conduit Artery Function Evaluation (CAFE) study".
PMID- 17030698
TI - Letter by Safar and Fournier regarding article, "Differential impact of blood
pressure-lowering drugs on central aortic pressure and clinical outcomes:
principal results of the Conduit Artery Function Evaluation (CAFE) study".
PMID- 17030699
TI - Viewpoint: Heart failure and anaemia--a concept returns to the fore.
PMID- 17030701
TI - The inflammatory hypothesis: any progress in risk stratification and therapeutic
targets?
PMID- 17030702
TI - Th1 adaptive immune responses in cardiac graft arteriosclerosis: deleterious or
beneficial?
PMID- 17030703
TI - The heart of trained athletes: cardiac remodeling and the risks of sports,
including sudden death.
PMID- 17030704
TI - Atrial septal defects in the adult: recent progress and overview.
PMID- 17030705
TI - Factors predicting intraocular pressure control after phacoemulsification in
angle-closure glaucoma.
AB - OBJECTIVES: To investigate whether the presence of glaucomatous optic neuropathy
affects the reduction of intraocular pressure (IOP) after phacoemulsification in
postiridotomy eyes with primary narrow angles, and to evaluate the preoperative
factors associated with postoperative IOP control in primary angle-closure
glaucoma (PACG). METHODS: Patients with PACG undergoing phacoemulsification were
prospectively enrolled and received a complete ophthalmic examination. Diurnal
IOP was measured 1 day before and 3 months after surgery. For comparison,
patients with primary angle closure or angle closure suspect (PAC/S) undergoing
phacoemulsification were also enrolled. RESULTS: Postoperative reduction of IOP
was significant in the PACG group (n = 29; P = .001) and in the PAC/S group (n =
28; P<.001), with no significant difference between the groups. The number of
glaucoma medications used decreased in both groups (both, P<.001). Multiple
regression analysis for the PACG group showed that there was a positive
correlation between postoperative IOP and preoperative factors of mean IOP (P =
.001) and the anterior chamber depth (P = .03). CONCLUSIONS: The reduction of IOP
3 months after phacoemulsification is significant and is similar in extent in
postiridotomy eyes with and without glaucomatous optic neuropathy. A higher
postoperative IOP in PACG is associated with a higher preoperative IOP and with a
deeper preoperative anterior chamber depth.
PMID- 17030706
TI - Novel approach for anterior chamber angle analysis: anterior chamber angle
detection with edge measurement and identification algorithm (ACADEMIA).
AB - OBJECTIVE: To describe a novel approach to measuring anterior chamber angle
dimensions and configurations. METHODS: Sixty-nine images were selected randomly
from the ultrasound biomicroscopic image database to develop the algorithm.
Thirty images were selected for further analyses. The value of each pixel of the
8-bit grayscale ultrasound biomicroscopic images was quantized into 0 (black) or
1 (white), and the edge points outlining the angle were detected and fitted with
straight lines. The dimensions and profiles of anterior chamber angles were then
measured. RESULTS: The algorithm failed to identify the edge points correctly in
8 (11.6%) of 69 images because of strong background noise. Three basic types of
angle configuration were identified based on the derived angle profiles:
constant, increasing, and decreasing, which corresponded to flat, bowed forward,
and bowed backward iris contours, respectively. The angle measurements
demonstrated high correlation with trabecular-iris angle and angle opening
distance 500 (calculated as the distance from the corneal endothelium to the
anterior iris surface perpendicular to a line drawn at 500 mum from the scleral
spur). The strongest association was found between the averaged angle derived
from the angle profile and the angle opening distance 500 (r = 0.91). CONCLUSION:
The proposed algorithm has high correlations with angle opening distance and
trabecular-iris angle with the added advantages of being fully automated,
reproducible, and able to capture the characteristic angle configurations.
However, good-quality ultrasound biomicroscopic images with high signal-to-noise
ratio are required to identify the edge points correctly.
PMID- 17030707
TI - Relative risk of progressive glaucomatous visual field loss in patients enrolled
and not enrolled in a prospective longitudinal study.
AB - OBJECTIVE: To establish the relative risk of progressive visual field loss in a
sample of glaucomatous eyes enrolled in a prospective longitudinal study vs a
matched sample of eyes not enrolled in a study. METHODS: The first visual field
records of 66 glaucomatous eyes enrolled in a prospective longitudinal study
(mean follow-up time, 3.4 years; mean number of visual field tests, 8.3) were
matched to 66 eyes from patients not enrolled in a study (mean follow-up time, 3
years; mean number of visual field tests, 3.7). Eyes were matched on the basis of
(1) time of enrollment, (2) length of follow-up, and (3) the extent and spatial
pattern of visual field loss. Linear regression of global visual field indexes
was used to measure change and the relative risk of progression was calculated
for a series of progression criteria sample. RESULTS: The relative risk of
progressive visual field loss was on average 368% (range, 209%-673%) higher in
the eyes not enrolled in a prospective longitudinal study. CONCLUSION: Selection
bias may reduce the risk of progressive visual field loss in patients enrolled in
longitudinal studies.
PMID- 17030708
TI - Optical coherence tomography in group 2A idiopathic juxtafoveolar retinal
telangiectasis.
AB - OBJECTIVE: To describe the changes observed with optical coherence tomography in
group 2A idiopathic juxtafoveolar retinal telangiectasis. METHODS: We
retrospectively reviewed the medical records of 13 patients (25 eyes). All eyes
underwent optical coherence tomography examination consisting of 6 radial scans,
fundus color photography, and fluorescein angiography. We calculated retinal
foveal and central foveal thicknesses from software mapping results. We compared
the optical coherence tomography data with fundus photography and fluorescein
angiography findings. RESULTS: Foveal cystoid spaces, very small or more
prominent, were present in 20 of 25 eyes. Some degree of disruption of the inner
segment/outer segment photoreceptor junction line was observed in 18 eyes as from
stage 2 of idiopathic juxtafoveolar retinal telangiectasis, and intraretinal
pigmentary proliferation was observed in 9. A foveal detachment without
subretinal new vessels was also present in 2 eyes. Despite these abnormalities,
central foveal thickness was below or within the range of reference values in all
eyes; foveal thickness, in 23 of 25. In the more advanced cases, severe
disruption of the inner segment/outer segment photoreceptor junction line and
outer retinal atrophy were seen. CONCLUSIONS: Early in the evolution of group 2A
idiopathic juxtafoveolar retinal telangiectasis, the optical coherence tomography
examination disclosed intraretinal cystoid spaces without foveal thickening and
disruption of the inner segment/outer segment photoreceptor junction line. Foveal
thinning was present in later stages.
PMID- 17030709
TI - Electrophysiological findings in patients with dengue-related maculopathy.
AB - OBJECTIVE: To assess visual function in patients with dengue maculopathy using
electrophysiological tests. METHODS: Fifteen consecutive patients with dengue
fever who experienced vision loss between July 2004 and July 2005 were included
in this review. Full-field electroretinograms (ERG), pattern ERGs, and multifocal
ERGs were performed. RESULTS: The most common electrophysiological finding (60%,
9/15) was a normal or mildly abnormal full-field ERG with reduced pattern ERG P50
amplitude and abnormal mfERG. Typically, multifocal ERG demonstrated a focal area
of decreased macular response (especially between the fovea and optic nerve).
Pattern ERG suggested normal optic nerve function in all but 1 case. Four
patients had more severely reduced full-field ERG responses with reduced a-wave
amplitude (suggestive of photoreceptor dysfunction), 3 of whom had an
electronegative maximal response (suggestive of additional postreceptor
dysfunction). Repeat multifocal ERG showed little change in 7 patients and
incomplete resolution in 2 patients over 3 to 10 months. CONCLUSION: Retinal
dysfunction associated with dengue maculopathy was localized mainly around the
foveal region. It appeared to affect the outer and middle retina more severely
with relative sparing of the inner retina. Retinal dysfunction may persist for
several months. Longer follow-up is required to determine whether these changes
are permanent.
PMID- 17030710
TI - Vascular endothelial growth factor a in eyes with uveal melanoma.
AB - OBJECTIVES: To determine the presence of vascular endothelial growth factor A
(VEGF-A) in the aqueous humor of eyes with uveal melanoma and to identify its
source. METHODS: The VEGF-A concentrations were determined in aqueous humor
samples obtained after enucleation from 74 eyes with untreated uveal melanoma and
from 8 eyes with treated uveal melanoma. Patient survival and clinical and
histopathological tumor variables were compared. In situ hybridization, Western
blot analysis, and enzyme-linked immunosorbent assay were used to determine
expression of VEGF-A in tumor tissue and in overlying retina. RESULTS: Aqueous
VEGF-A concentrations ranged from 18 to 826 pg/mL in 74 untreated eyes, while
concentrations in 30 control eyes were significantly lower (median, 50.1 pg/mL)
(P<.001). Concentrations in 8 treated eyes were much higher (median, 364 pg/mL).
In situ hybridization on tissue sections and Western blot analysis and enzyme
linked immunosorbent assay on tissue extracts revealed VEGF-A in uveal melanoma
tissue and in retinal tissue. CONCLUSIONS: Uveal melanoma is associated with
increased concentrations of VEGF-A in aqueous humor. Aqueous VEGF-A concentration
correlates with largest basal tumor diameter and with the tumor height. In eyes
with uveal melanoma, tumor and retinal tissues are sources of VEGF-A.
PMID- 17030711
TI - Amniotic membrane transplantation in children with symblepharon and massive
pannus.
AB - OBJECTIVE: To report our pediatric experience with amniotic membrane
transplantation for ocular surface and forniceal reconstruction. METHODS:
Retrospective case review of children who underwent superficial keratectomy,
symblepharon lysis, and forniceal reconstruction using amniotic membrane
transplantation. The underlying diagnosis, visual acuity, level of discomfort at
first and last visits, and surgical details were noted. RESULTS: Four patients (5
eyes) were included. Two patients had epidermolysis bullosa (1 recessive
dystrophic and 1 junctional), 1 had laryngo-onychocutaneous syndrome, and 1 had
measles-related keratitis and was positive for human immunodeficiency virus.
Their mean age when initially seen was 8.7 years (age range, 4-16 years), and
mean follow-up was 18.25 months (range, 12-29 months). The mean visual acuity
preoperatively was 1.1 logMAR (logarithm of the minimum angle of resolution)
(range, 1-1.3), and postoperatively was 0.7 (range, 0.2-1.2). All patients
experienced increased ocular comfort with anatomical restoration of corneal and
conjunctival surfaces. Visual acuity improved in 3 eyes. Only the patient with
laryngo-onychocutaneous syndrome had recurrence of granuloma, at 9 months after
surgery. CONCLUSION: Amniotic membrane transplantation with symblepharon lysis is
effective for ocular surface reconstruction in the management of epidermolysis
bullosa and other conditions that cause corneal scarring and symblepharon in
children. In this small series, children with epidermolysis bullosa fared better
and the effects of surgery lasted longer compared with patients with other causes
of symblepharon and massive pannus.
PMID- 17030712
TI - Bioengineered human corneal endothelium for transplantation.
AB - OBJECTIVE: To investigate whether the bioengineered human corneal endothelial
cell (HCEC) monolayers harvested from thermoresponsive culture supports could be
used as biological tissue equivalents. METHODS: Untransformed adult HCECs derived
from eye bank corneas were cultivated on a thermoresponsive poly-N
isopropylacrylamide-grafted surface for 3 weeks at 37 degrees C. Confluent cell
cultures with a phenotype and cell density similar to HCECs in vivo were detached
as a laminated sheet by lowering the culture temperature to 20 degrees C. In
vitro characteristics of the HCEC sheets were determined evaluating their
viability and by scanning electron microscopy, immunohistochemistry, and
histological studies. RESULTS: After separation from culture surfaces via a
thermal stimulus, the HCEC sheets remained viable. Polygonal cell morphology and
multiple cellular interconnections were observed throughout the HCEC sheets.
Immunolocalization of zonula occludens-1 and Na+,K+-adenosine triphosphatase
(ATPase) indicated the formation of tight junctions and the distribution of ionic
pumps at the cell boundary. In addition, we ascertained that cultured HCECs have
a monolayered architecture that mimics native corneal endothelium. CONCLUSION:
These data suggest that a well-organized and functional HCEC monolayer can
feasibly be used as tissue equivalents for replacing compromised
endothelium.Clinical Relevance Bioengineered human corneal endothelium fabricated
from thermoresponsive supports can potentially offer a new therapeutic strategy
for corneal endothelial cell loss.
PMID- 17030713
TI - Altered tear composition in smokers and patients with graves ophthalmopathy.
AB - OBJECTIVES: To analyze, compare, and contrast tear composition in healthy
nonsmokers, smokers who were otherwise healthy, and patients with Graves disease
(GD) accompanied by Graves ophthalmopathy (GO) of varying severity. METHODS:
Reflex tears were collected using Schirmer strips from 37 healthy nonsmokers, 33
otherwise healthy smokers, 51 patients with GD, and 85 patients with GO.
Thyrotropin receptor-stimulating activity and serum thyroid-stimulating
antibodies were measured. Pooled tear samples from healthy nonsmokers, healthy
smokers, and patients with GO were separated by means of electrophoresis.
Proteins expressed in healthy smokers, patients with GO, and healthy nonsmokers
were separated by means of electrophoresis and analyzed by mass spectrometry.
RESULTS: Based on the 97th percentile of findings from healthy nonsmokers,
specific thyrotropin receptor-stimulating activity was detected in 25% of the
tear samples from healthy smokers, 32% of those from patients with GD, and 41% of
those from patients with GO. Clinical activity scores correlated with serum
thyroid-stimulating antibody levels but not tear thyrotropin receptor-stimulating
activity. Electrophoresis revealed additional proteins of 30 to 41 kDa in the
tear samples from patients with GO and healthy smokers compared with samples from
healthy nonsmokers. These proteins were identified as zinc-alpha2-glycoprotein
and lactoferrin but have no thyrotropin receptor-stimulating activity.
CONCLUSIONS: We demonstrate similar changes in tear composition in patients with
GO and healthy smokers compared with healthy nonsmokers. Expression of zinc
alpha2-glycoprotein and lactoferrin is increased and their molecular weights are
modified, suggesting degradation and/or changes during glycosylation, which may
affect the bioactivities of zinc-alpha2-glycoprotein and lactoferrin. Clinical
Relevance Smoking, which is a significant risk factor for the development of GO,
modifies tear composition.
PMID- 17030714
TI - Association of connective tissue growth factor with fibrosis in vitreoretinal
disorders in the human eye.
AB - OBJECTIVE: To investigate the expression of the profibrotic connective tissue
growth factor (CTGF) in relation to severity of intraocular fibrosis and
neovascularization in human vitreoretinal disorders for the identification of
potential therapeutic targets to prevent fibrosis. METHODS: Concentrations of
CTGF were measured by enzyme-linked immunosorbent assay in 119 vitreous samples
from patients with proliferative diabetic retinopathy, proliferative
vitreoretinopathy, epiretinal membrane, and macular hole. Clinical data,
including degree of intraocular fibrosis and neovascularization, were collected
using standardized forms. RESULTS: Multifactorial analysis revealed that only
CTGF levels correlated highly significantly with degree of fibrosis in the
various vitreoretinal disorders studied (P<.001; R2= 47.7%). Likewise, variation
in degree of fibrosis was best predicted by CTGF levels (P<.001). CONCLUSION: The
strong correlation between CTGF levels and degree of fibrosis in vitreoretinal
disorders suggests that CTGF is an important factor in ocular fibrosis, similar
to its role in pathologic fibrosis in other organs. CLINICAL RELEVANCE:
Connective tissue growth factor may be a therapeutic target for prevention of
sight-threatening vitreoretinal scarring in the eye.
PMID- 17030715
TI - Association between vision and hearing impairments and their combined effects on
quality of life.
AB - OBJECTIVES: To assess associations between age-related vision and hearing
impairments and whether combined sensory losses magnify effects on health-related
quality of life. METHODS: Seventy-five percent of survivors (n = 2334) were
reexamined at Blue Mountains Eye Study 5-year examinations and 86.3% (2015)
attended hearing assessments. Visual impairment was defined as visual acuity less
than 20/40 (better eye), and hearing impairment as average pure-tone air
conduction threshold greater than 25 dB (500-4000 Hz, better ear). RESULTS:
Persons with visual impairment, compared with those without visual impairment,
had lower mean audiometric thresholds across all frequencies (P< or =.05). For
each 1-line (5-letter) reduction in best-corrected visual acuity and presenting
visual acuity, hearing loss prevalence increased by 18% and 13%, respectively.
Cataract and age-related maculopathy were also associated with hearing loss
(respectively, multivariate-adjusted odds ratio, 1.3 and 1.6; 95% confidence
interval, 1.0-1.7 and 1.1-3.1). The association between age-related maculopathy
and hearing loss was stronger at younger ages (<70 years). Combined impairments
were associated with poorer health-related quality of life than were single
impairments (multivariate-adjusted 36-Item Short-Form Health Survey mean physical
and mental component scores; Ptrend = .001 and <.001, respectively). CONCLUSIONS:
Older persons with visual impairment were also more likely to have hearing loss
in this study, which suggests that these sensory impairments could share common
risk factors or biologic aging markers. Combined sensory impairments also
cumulatively affect health-related quality of life.
PMID- 17030716
TI - Effect of medical therapy on glaucoma filtration surgery rates in Ontario.
AB - OBJECTIVE: To analyze trends of glaucoma filtration surgery in Ontario. METHODS:
From April 1, 1992, through March 31, 2004, correlations were examined between
the annual rates of trabeculectomies in Ontario, the use of glaucoma medications,
and the numbers of practicing ophthalmologists and optometrists. RESULTS: The
number of trabeculectomies per 1000 persons at risk for primary open-angle
glaucoma increased from 33.5 in 1992 to 46.2 in 1996 (37.7% increase; 6.6%
increase per year) and then steadily decreased to 38.2 in 2004 (17.0% decrease;
2.7% decrease per year). The number of glaucoma medications dispensed in Ontario
increased from 766 000 in 1992 to 1 466 543 in 2004 (91.5% increase; 10.5% annual
increase). The increase in dispensed prostaglandin analogues strongly correlated
(P<.001; 95% confidence interval, -0.87 to -0.41) with the decreasing number of
trabeculectomies. The decreasing number of ophthalmologists positively correlated
(r = 0.87) with the filtration surgery rate after 1997. CONCLUSIONS: The number
of trabeculectomies has decreased substantially in Ontario coinciding with the
introduction of medications for the treatment of glaucoma in December 1996. This
decrease in trabeculectomies highly correlated with the introduction of
prostaglandin analogues (P<.001) and the decreasing number of ophthalmologists
from 1997 through 2004.
PMID- 17030717
TI - What we don't know about avastin might hurt us.
PMID- 17030719
TI - Ophthalmology in Venezuela.
PMID- 17030718
TI - Ophthalmology from ancient Persia to the modern era.
PMID- 17030720
TI - Histopathology and ultrastructure of human corneas after amniotic membrane
transplantation.
PMID- 17030721
TI - Presenile cataract: consider cholestanol.
PMID- 17030722
TI - Familial retinal arterial tortuosity associated with tortuosity in nail bed
capillaries.
PMID- 17030723
TI - Congenital iris ectropion and glaucoma associated with intestinal neuronal
dysplasia: a manifestation of a neural crest syndrome.
PMID- 17030724
TI - Iris ectopic thyroid tissue: report of a case.
PMID- 17030725
TI - Ligneous conjunctivitis in a Mexican patient with a mutation in the plasminogen
(PLG) gene.
PMID- 17030726
TI - Melioidosis with endophthalmitis.
PMID- 17030727
TI - Delayed Nd:YAG laser membranotomy for traumatic premacular hemorrhage.
PMID- 17030728
TI - A transilluminating scleral lesion.
PMID- 17030729
TI - Optimizing the use of tumor necrosis factoralpha inhibitors in refractory
uveitis.
PMID- 17030730
TI - Intravitreal triamcinolone in diabetic macular edema.
PMID- 17030731
TI - Optic nerve structure in healthy subjects.
PMID- 17030732
TI - Acute respiratory distress due to verteporfin infusion for photodynamic therapy.
PMID- 17030733
TI - Risk of Lasik surgery vs contact lenses.
PMID- 17030734
TI - The eyes and brain of Johann Sebastian Bach.
PMID- 17030735
TI - DDD mice, a novel acute mouse model of Parkinson's disease.
AB - We describe the development of a novel animal model of acute severe dopamine (DA)
deficiency by using genetically altered mice lacking the DA transporter (DAT-KO
mice). In the absence of a DAT-mediated recycling mechanism in these mice,
striatal DA concentrations become entirely dependent on its de novo synthesis,
and acute pharmacologic inhibition of tyrosine hydroxylase induces transient (up
to 16 hours) elimination of brain DA. Dopamine-deficient DAT-KO mice (DDD mice)
demonstrate a striking behavioral phenotype manifested as severe akinesia,
rigidity, tremor, and ptosis. We propose that DDD mice represent a novel acute
model of severe DA deficiency that might be used to identify compounds with
potential therapeutic use for the treatment of Parkinson's disease (PD). This
model is particularly promising as a tool for evaluating the efficacy of
compounds that may induce movement independently of DA. The advantages and
limitations of DDD mice in comparison to other rodent PD models are discussed.
PMID- 17030736
TI - Safinamide: from molecular targets to a new anti-Parkinson drug.
AB - Ideal treatment in Parkinson's disease (PD) aims at relieving symptoms and
slowing disease progression. Of all remedies, levodopa remains the most effective
for symptomatic relief, but the medical need for neuroprotectant drugs is still
unfulfilled. Safinamide, currently in phase III clinical trials for the treatment
of PD, is a unique molecule with multiple mechanisms of action and a very high
therapeutic index. It combines potent, selective, and reversible inhibition of
MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of
glutamate release. Safinamide has neuroprotective and neurorescuing effects in
MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model.
Safinamide potentiates levodopa-mediated increase of DA levels in DA-depleted
mice and reverses the waning motor response after prolonged levodopa treatment in
6-OHDA-lesioned rats. Safinamide has excellent bioavailability, linear kinetics,
and is suitable for once-a-day administration. Therefore, safinamide may be used
in PD to reduce l-dopa dosage and also represents a valuable therapeutic drug to
test disease-modifying potential.
PMID- 17030737
TI - Symptom relief in Parkinson disease by safinamide: Biochemical and clinical
evidence of efficacy beyond MAO-B inhibition.
AB - In an open pilot study, doses of safinamide (100, 150, and 200 mg once a day,
higher than previously tested) were administered to 13 parkinsonian patients
along with a stable dose of dopamine (DA) agonist, causing a significant
progressive improvement in motor performance as evaluated by the Unified
Parkinson Disease Rating Scale (UPDRS) part III over an 8-week period (4.2
points; P < 0.001). In association with levodopa, the same doses of safinamide in
another group of patients (N = 11) induced a significant decrease in motor
fluctuations (UPDRS part IV, 2.1 points; P < 0.001), accompanied by a dose
proportional increase of the levodopa AUC, up to 77% from baseline. Because MAO-B
was fully inhibited (95%) at all doses tested, we suggest that these biochemical
and symptomatic dose-dependent effects must be related to additional mechanisms
of action, such as inhibition of glutamate release, increased dopamine release,
or inhibition of dopamine re-uptake. These hypotheses are under investigation and
will pursue confirmation in controlled clinical trials.
PMID- 17030738
TI - New pharmacologic horizons in the treatment of Parkinson disease.
AB - Many of the motoric features that define Parkinson's disease (PD) result
primarily from the loss of dopaminergic neurons of the substantia nigra. l-dopa
remains at present the most powerful symptomatic drug for the treatment of this
condition. However, motor complications of chronic l-dopa treatment have emerged
as a major limitation of this therapy. Slowing or delaying the progression of the
disease with neuroprotective therapies may delay the need for l-dopa. In the past
few years, novel insight into the pathogenetic mechanisms of neurodegeneration in
PD has been provided. Mitochondrial function deficiency, increased oxidative
stress, apoptosis, excitotoxicity, and inflammation are part of the processes
that ultimately result in neurodegeneration. Drugs that are now under clinical
scrutiny as neuroprotectant include molecules that combine one or more of the
following properties: (1) monoamine oxidase inhibition (rasagiline, safinamide);
(2) mitochondrial enhancement (coenzyme Q10, creatine); (3) antiapoptotic
activity; (4) anti-inflammatory activity; (5) protein aggregation inhibition; (6)
neurotrophic activity. In advanced Parkinson's disease, the combination of
disease progression and l-dopa therapy leads to the development of motor response
complications, particularly wearing off, on off, dyskinesias and dystonias. The
nonphysiologic pulsatile stimulation of striatal dopamine receptors, produced by
the currently available dopaminergic drugs, may trigger a dysregulation of many
neurotransmitter systems within the basal ganglia, mainly localized on medium
spiny striatal neurons. These include alterations of glutamatergic, serotonergic,
adrenergic and adenosine A(2A) receptors. Novel strategies for pharmacological
intervention with nondopaminergic treatments hold the promise of providing
effective control or reversal of motor response complications. Of particular
interest are NMDA and AMPA antagonists or drugs acting on 5-HT subtype 2A, alpha2
adrenergic, and adenosine A(2) receptors. Future strategies may also target pre-
and postsynaptic components that regulate firing pattern of basal ganglia
neurons, such as synaptic vesicle proteins, nonsynaptic gap junction
communication mechanisms, or signal transduction systems that modulate the
phosphorylation state of glutamatergic receptors.
PMID- 17030739
TI - Structure of the human mitochondrial monoamine oxidase B: new chemical
implications for neuroprotectant drug design.
AB - Monoamine oxidase B (MAO-B) is an outer mitochondrial membrane-bound flavoenzyme
that is a well-known target for antidepressant and neuroprotective drugs. The 3A
resolution structure of recombinant human MAO-B originally determined was of the
enzyme complexed with pargyline, an irreversible inhibitor covalently bound to
the N5 atom of the flavin coenzyme. The crystal structure shows that the enzyme
is dimeric. Each monomer binds to the membrane via a C-terminal transmembrane
helix and by apolar loops located at various positions in the sequence. Substrate
binding to the enzyme involves negotiating a loop covering a 290A3 entrance
apolar cavity before reaching an apolar 420A3 substrate cavity where the flavin
coenzyme is located. The 1.7A isatin-MAO-B structure allowed a detailed
examination of the enzyme's active site. A novel specific reversible MAO-B
inhibitor, which is found as a contaminant in polystyrene plastics (1,4-diphenyl
2-butene), binds in both the entrance and the substrate cavity. Analogous MAO-B
specific inhibitors that bind in a manner traversing both cavities include trans
trans farnesol and chlorostyrylcaffeine. The rotation of the Ile199 side chain to
an "open" conformation plays an essential role in this specificity. These results
form a molecular basis for the design of new human MAO-B-specific reversible
inhibitors.
PMID- 17030740
TI - A proposed dual role of neuromelanin in the pathogenesis of Parkinson's disease.
AB - In many parkinsonian syndromes, neuromelanin (NM)-containing dopaminergic neurons
of the substantia nigra (SN) are selectively targeted by the noxius pathogens.
Studies of the constitutional and functional features of human NM allow the
formulation of a logical hypothesis on its role in parkinsonian syndromes. In the
early stages, NM synthesis and iron-chelating properties may act as a powerful
protective mechanism, delaying symptom appearance and/or slowing disease
progression. Once these systems have been exhausted, the pathogenic mechanisms
affecting cytoplasmic organelles other than NM destroy NM-harboring neurons, with
consequent pouring out of NM granules. These in turn activate microglia, causing
release of nitric oxide, interleukin-6 and tumor necrosis factor-alpha, thus
becoming an important determinant of disease aggravation. Neuromelanin appears to
be a suitable target for devising chemical agents that might modify the course of
these diseases.
PMID- 17030741
TI - A "nerve" ending story in the identification of mutations in Charcot-Marie-Tooth
neuropathy.
PMID- 17030742
TI - Gabapentin in the operating room: clear for discharge?
PMID- 17030743
TI - Repetitive and impulsive behaviors in treated Parkinson disease.
PMID- 17030745
TI - Risk of ischemic complications related to the intensity of triptan and ergotamine
use.
AB - OBJECTIVE: To investigate whether the intensity of triptan and ergotamine use, in
specific overuse, is associated with the risk of ischemic complications. METHODS:
We conducted a retrospective nested case-control study using data from the PHARMO
Record Linkage System. All patients with more than one prescription for either a
triptan or ergotamine were initially identified. Cases were all patients who were
admitted to the hospital for an ischemic complication. Matched controls were
assigned the same index date as the cases. The determinant was the intensity of
use of triptans and ergotamine during 1 year preceding the index date. Overuse
was defined as use of > or =90 defined daily doses during that year. Conditional
logistic regression was used to estimate odds ratios (ORs), adjusting for
confounders. Stratified analysis was used to estimate the risk for both patients
using and those not using cardiovascular drugs. RESULTS: A total of 17,439
patients received more than one prescription. A total of 188 cases and 689
controls were identified. Triptan overuse was not associated with an increased
risk of ischemic complications (OR 0.96; 95% CI: 0.49 to 1.90). Overuse of
triptans in patients concomitantly using cardiovascular drugs did not increase
this risk. Overuse of ergotamine turned out to be a risk factor for ischemic
complications (OR 2.55; 95% CI: 1.22 to 5.36). Patients overusing ergotamine and
concomitantly using cardiovascular drugs were at highest risk (OR 8.52; 95% CI
2.57 to 28.2). CONCLUSIONS: In general practice, triptan overuse does not
increase the risk of ischemic complications. Overuse of ergotamine may increase
the risk of these complications, especially in those simultaneously using
cardiovascular drugs.
PMID- 17030744
TI - Treatment of neurocysticercosis: current status and future research needs.
AB - Here we put forward a roadmap that summarizes important questions that need to be
answered to determine more effective and safer treatments. A key concept in
management of neurocysticercosis is the understanding that infection and disease
due to neurocysticercosis are variable and thus different clinical approaches and
treatments are required. Despite recent advances, treatments remain either
suboptimal or based on poorly controlled or anecdotal experience. A better
understanding of basic pathophysiologic mechanisms including parasite survival
and evolution, nature of the inflammatory response, and the genesis of seizures,
epilepsy, and mechanisms of anthelmintic action should lead to improved
therapies.
PMID- 17030746
TI - Skin biopsies demonstrate MPZ splicing abnormalities in Charcot-Marie-Tooth
neuropathy 1B.
AB - OBJECTIVE: To demonstrate that intronic mutations in the myelin protein zero
(MPZ) cause Charcot-Marie-Tooth neuropathy 1B (CMT1B) by disrupting MPZ splicing.
METHODS: We report a family with a T>G transversion at the invariant + 2 position
in intron 4 of MPZ (c.614 + 2T>G) that abolishes 5' donor site recognition and is
predicted to alter MPZ splicing. We obtained detailed clinical and
neurophysiologic analysis of the family. We performed skin biopsies to
investigate splicing abnormalities, MPZ protein levels, and localization in
myelinated nerves. RESULTS: Patients developed a late onset neuropathy with
minimally slow nerve conduction velocities. Skin biopsies confirmed the predicted
skipping of exon 4 and downstream frameshift of the mutant MPZ. Quantitative
immuno-EM demonstrated normal nerve MPZ levels, suggesting that the mutant MPZ
was transported to compact myelin. CONCLUSIONS: Intronic mutations cause CMT1B by
disrupting splicing and certain MPZ mutations may cause neuropathy by interacting
with the wild type MPZ in the extracellular space of compact myelin.
PMID- 17030747
TI - Posttraumatic cerebral infarction in patients with moderate or severe head
trauma.
AB - OBJECTIVE: To evaluate the frequency, types, and location of posttraumatic
cerebral infarction, to assess if secondary cerebral insults were associated with
cerebral infarction, and to determine if cerebral infarction affected patients'
outcome. METHODS: We based diagnosis of cerebral infarction on review of brain CT
scans. We assessed frequency of secondary cerebral insults, including
intracranial hypertension, cerebral hypoperfusion, systolic hypo- and
hypertension, arterial blood oxygen desaturation, hypocapnia, and hyperthermia,
using clinical charts. We used the Glasgow Outcome Scale to evaluate outcome at 6
months after trauma. RESULTS: Of the 89 patients included, a total of 28 cerebral
infarctions were found in 17 cases (19.1%). Infarctions were territorial in 23
(82.1%) and watershed in 5 (17.9%) cases. Territorial infarctions were localized
to the middle cerebral artery (n = 9, 32.1%), lenticulostriate arteries (n = 6,
21.4%), posterior cerebral artery (n = 3, 10.7%), anterior cerebral artery (n =
3, 10.7%), thalamoperforating arteries (n = 1, 3.6%), and basilar artery (n = 1,
3.6%) territories. Watershed infarctions were in the boundary (n = 4, 14.3%) and
terminal (n = 1, 3.6%) zones. Intracranial hypertension was the only independent
variable predicting cerebral infarction (odds ratio [OR] 13.3; 95% CI 2.8 to
62.6). At 6 months after trauma, there was a lower proportion of patients with
good outcome among patients with cerebral infarction vs patients without (23.5
and 61.1%; p = 0.005). Cerebral infarction was the only independent predictor of
6-month outcome (OR of good outcome 0.19, 95% CI 0.06 to 0.66). CONCLUSIONS: The
risk of developing posttraumatic cerebral infarction may be higher in patients
with intracranial hypertension than in those without. Patients with posttraumatic
cerebral infarction may be at increased risk of residual disability.
PMID- 17030748
TI - Micro- and macroalbuminuria predict hemorrhagic transformation in acute ischemic
stroke.
AB - BACKGROUND: Hemorrhagic transformation (HT) after cerebral ischemia seems to be
related to the endothelial disruption secondary to the ischemic process.
Albuminuria has recently been found to be a marker of chronic endothelial damage.
OBJECTIVE: To investigate the relationship between albuminuria and HT in patients
with acute ischemic stroke. METHODS: We studied 200 patients (51.5% men, age 72.5
+/- 8.5 years) with ischemic stroke within the first 24 hours of evolution. HT
development was assessed on CT performed between days 4 and 7 of evolution and
classified according to the ECASS II criteria. Urinary samples were collected
within the first 3 hours after admission and the presence of albuminuria, which
was considered to be present when the ratio albumin-to-creatinine was > or =30
mg/g creatinine, was determined by nephelometry within the first 24 hours of
evolution. RESULTS: Forty-nine patients (24.5%) had albuminuria and 36 (18%) had
HT on the second CT scan. After adjusting for potential confounders including a
previous history of diabetes mellitus, hypertension and atrial fibrillation,
stroke severity, the presence of early signs of ischemia and leukoaraiosis on the
baseline CT scan, and IV anticoagulant treatment, logistic regression analysis
showed that albuminuria was independently associated with HT (OR, 7.45; 95% CI
2.30 to 24.16). Moreover, albuminuria was also a significant and independent
predictor of parenchymal hemorrhage type 1 and 2 (OR, 8.30; 95% CI 1.77 to
38.89). CONCLUSION: Albuminuria is an independent predictor of hemorrhagic
transformation, and particularly of the most severe bleedings, in patients with
acute ischemic stroke. Due to the small number of events, the predictive capacity
of albuminuria should be confirmed in larger studies.
PMID- 17030749
TI - Cerebellar infarction presenting isolated vertigo: frequency and vascular
topographical patterns.
AB - OBJECTIVE: To determine the frequency of cerebellar infarction mimicking
vestibular neuritis (VN), the pattern of clinical presentation, and the territory
of the cerebellar infarction when it simulates VN. METHODS: We studied 240
consecutive cases of isolated cerebellar infarction in the territories of the
cerebellar arteries diagnosed by brain MRI from the acute stroke registry at the
Keimyung University Dongsan Medical Center. RESULTS: We identified 25 patients
(10.4%) with isolated cerebellar infarction who had clinical features suggesting
VN. Two types of cerebellar infarction simulating VN were found: isolated
spontaneous prolonged vertigo with imbalance as a sole manifestation of
cerebellar infarction (n = 24) and isolated spontaneous prolonged vertigo with
imbalance as an initial manifestation of cerebellar infarction (n = 1) followed
by delayed neurologic deficits 2 days after the onset. The cerebellar infarction
territory most commonly involved was the medial branch of the posterior inferior
cerebellar artery territory (24/25: 96%), followed by the anterior inferior
cerebellar artery territory (1/25: 4%). None of patients with infarcts in the
territory of the superior cerebellar artery or multiple cerebellar arteries
showed isolated spontaneous prolonged vertigo. CONCLUSIONS: Cerebellar infarction
simulating vestibular neuritis is more common than previously thought. Early
recognition of the pseudo-vestibular neuritis of vascular cause may allow
specific management.
PMID- 17030750
TI - Association of aortic plaque with intracranial atherosclerosis in patients with
stroke.
AB - OBJECTIVE: To determine whether there is a relationship between aortic plaques
and intracranial (IC) atherosclerosis. METHODS: We reviewed 922 patients with
stroke who had both transesophageal echocardiography and cerebral angiography.
The plaques of these patients were classified as either complex aortic plaques
(CAP), which protruded > or =4 mm or were present as mobile lesions in the
proximal aorta, or simple aortic plaques (SAP), which were <4 mm or present in
the descending aorta. Cerebral artery atherosclerosis was classified as either an
IC or extracranial (EC) atherosclerosis. RESULTS: Among the 922 patients, we
found aortic plaques in 237 patients (26%). There were 111 (47%) patients of SAP,
74 (31%) patients with CAP, and 52 (22%) patients that had both SAP and CAP.
Angiography showed IC or EC atherosclerosis in 511 patients (55%). The presence
of aortic plaques was significantly associated with IC or EC atherosclerosis. The
significance appeared to be due to the strong association between the presence of
SAP and IC atherosclerosis (51% SAP vs 35% no plaques; odds ratio = 1.94, 95% CI:
1.17 to 3.21). In the multiple logistic regression analysis, SAP were independent
predictors of IC atherosclerosis CONCLUSIONS: The presence of simple aortic
plaques may be a marker of advanced vascular disease. Detection of simple aortic
plaques during transesophageal echocardiography may have clinical implications
because patients with these plaques frequently had concomitant intracranial
atherosclerosis, a risk factor for stroke.
PMID- 17030751
TI - The Motor Activity Log-28: assessing daily use of the hemiparetic arm after
stroke.
AB - BACKGROUND: Data from monkeys with deafferented forelimbs and humans after stroke
indicate that tests of the motor capacity of impaired extremities can
overestimate their spontaneous use. Before the Motor Activity Log (MAL) was
developed, no instruments assessed spontaneous use of a hemiparetic arm outside
the treatment setting. OBJECTIVE: To study the MAL's reliability and validity for
assessing real-world quality of movement (QOM scale) and amount of use (AOU
scale) of the hemiparetic arm in stroke survivors. METHODS: Participants in a
multisite clinical trial completed a 30-item MAL before and after treatment (n =
106) or an equivalent no-treatment period (n = 116). Participants also completed
the Stroke Impact Scale (SIS) and wore accelerometers that monitored arm movement
for three consecutive days outside the laboratory. All were 3 to 12 months post
stroke and had mild to moderate paresis of an upper extremity. RESULTS: After an
item analysis, two MAL tasks were eliminated. Revised participant MAL QOM scores
were reliable (r =0.82). Validity was also supported. During the first
observation period, the correlation between QOM and SIS Hand Function scale
scores was 0.72. The corresponding correlation for QOM and accelerometry values
was 0.52. Participant QOM and AOU scores were highly correlated (r = 0.92).
CONCLUSIONS: The participant Motor Activity Log is reliable and valid in
individuals with subacute stroke. It might be employed to assess the real-world
effects of upper extremity neurorehabilitation and detect deficits in spontaneous
use of the hemiparetic arm in daily life.
PMID- 17030752
TI - Physical fitness and lifetime cognitive change.
AB - OBJECTIVE: To test the hypothesis that physical fitness is associated with more
successful cognitive aging. METHODS: Surviving participants (N = 460) of the
Scottish Mental Survey of 1932 were tested on the same general cognitive test at
age 11 and 79 years. Measures of grip strength, 6-meter walk time, and lung
function (forced expiratory volume from the lungs in 1 second [FEV1]) were
assessed at age 79 years. RESULTS: A latent physical fitness trait, derived by
principal components analysis of the three fitness measures, was significantly
associated with successful cognitive aging. Cognitive score at age 11, sex,
social class, and APOE-epsilon4 genotype were included as covariables. Higher
childhood IQ was associated with better lung function in old age. CONCLUSIONS:
Physical fitness is associated with cognitive reserve. Intervention studies aimed
at making older people fitter are good candidates to improve cognitive aging.
PMID- 17030753
TI - Ten-year risk of dementia in subjects with mild cognitive impairment.
AB - OBJECTIVE: To investigate the 10-year risk of dementia in subjects with mild
cognitive impairment (MCI) ages 40 to 85 years. METHODS: We selected subjects
from a memory clinic if they met one of the following definitions of MCI:
cognitive complaints (n = 181), aging-associated cognitive decline (AACD) (n =
163), mild functional impairment (n = 86), or amnestic MCI (n = 64). Subjects
were reassessed after 2, 5, and 10 years. The risk of dementia was calculated
with Kaplan-Meier statistics. Analyses were conducted in the entire sample and in
subgroups of subjects aged 40 to 54 years, 55 to 69 years, and 70 to 85 years.
RESULTS: The 10-year risk of dementia was 0.27 (95% CI 0.20 to 0.34) in subjects
with cognitive complaints, 0.28 (95% CI 0.21 to 0.35) in subjects with AACD, 0.44
(95% CI 0.32 to 0.56) in subjects with mild functional impairment, and 0.48 (95%
CI 0.35 to 0.61) in subjects with amnestic MCI. Ninety-one percent of the
demented subjects had probable AD. The risk of dementia increased with increasing
age for all MCI definitions (p < 0.001). Depending on the MCI definition used,
the risk for dementia ranged from 0 to 0.06 in subjects aged 40 to 54 years, from
0.37 to 0.52 in subjects aged 55 to 69 years, and from 0.77 to 1.0 in subjects
aged 70 to 85 years. CONCLUSIONS: The majority of subjects with MCI do not
progress to dementia at the long term. Age strongly influences the dementia risk.
MCI often represents the predementia stage of a neurodegenerative disorder in
elderly subjects but rarely in younger subjects.
PMID- 17030754
TI - Relation between body mass index and cognitive function in healthy middle-aged
men and women.
AB - OBJECTIVE: To assess whether body mass index (BMI) is associated with cognitive
function and cognitive decline in healthy men and women. METHODS: In this
prospective cohort study, we analyzed data from 2,223 healthy workers aged 32 to
62 years at baseline. Medical, psychosocial, and environmental data were
collected in 1996 and in 2001. We tested cognitive functions at baseline and at
follow-up with word-list learning (four recalls), a Digit-Symbol Substitution
Test, and a selective attention test. RESULTS: Cross-sectionally, a higher BMI
was associated with lower cognitive scores after adjustment for age, sex,
educational level, blood pressure, diabetes, and other psychosocial covariables.
A higher BMI at baseline was also associated with a higher cognitive decline at
follow-up, after adjustment for the above-cited confounding factors. This
association was significant for word-list learning. For the changes in scores at
word-list learning (delayed recall), regression coefficients were -0.008 +/-
0.13, -0.09 +/- 0.13, -0.17 +/- 0.14, and -0.35 +/- 0.14 (p for trend < 0.001)
for the second, third, fourth, and fifth quintiles of BMI at baseline when
compared with the first quintile. No significant association was found between
changes in BMI and cognitive function. CONCLUSIONS: Body mass index was
independently associated both with cognitive function (word-list learning and
Digit-Symbol Substitution Test) and changes in word-list learning in healthy,
nondemented, middle-aged men and women.
PMID- 17030755
TI - Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin
labeling MRI.
AB - OBJECTIVES: To test if arterial spin labeling (ASL) MRI could detect a pattern of
hypoperfusion in frontotemporal dementia (FTD) vs cognitively normal (CN) control
subjects; to determine the regional difference of perfusion between FTD and
Alzheimer disease (AD); and to determine whether hypoperfusion in FTD correlates
with cognitive impairment. METHODS: We included 21 patients with FTD, 24 patients
with AD, and 25 CN subjects in this cross-sectional MRI study. All subjects had
MRI scans including T1-weighted structural images and ASL-MR images. RESULTS: ASL
MRI detected a pattern of hypoperfusion in right frontal regions in patients with
FTD vs CN subjects, similar to PET and SPECT. FTD had higher perfusion than AD in
the parietal regions and posterior cingulate. Frontal hypoperfusion in FTD
correlated with deficits in judgment and problem solving. Adding frontal
perfusion to gray matter (GM) atrophy significantly improved the classification
of FTD from normal aging to 74%, and adding parietal perfusion to GM atrophy
significantly improved the classification of FTD from AD to 75%. Combining
frontal and parietal lobe perfusion further improved the classification of FTD
from AD to 87%. CONCLUSION: Frontotemporal dementia and Alzheimer disease display
different spatial distributions of hypoperfusion on arterial spin labeling MRI.
With further development and evaluation, arterial spin labeling MRI could
contribute to the differential diagnosis between frontotemporal dementia and
Alzheimer disease.
PMID- 17030756
TI - Regional brain atrophy in cognitively intact adults with a single APOE epsilon4
allele.
AB - OBJECTIVE: To determine whether cognitively intact adults with the APOE
epsilon3/epsilon4 genotype show reduced gray matter density on voxel-based
morphometry (VBM) vs those homozygous for the epsilon3 allele. METHODS:
Participants were healthy, cognitively intact, right-handed adults, age 19 to 80,
who completed genotyping, neuropsychological testing, and MRI. Forty-nine
participants had the epsilon3/epsilon3 genotype and 27 had the epsilon3/epsilon4
genotype. Gray matter data were analyzed using the general linear model as
implemented in the Statistical Parametric Mapping package, adjusting for age and
sex. RESULTS: The epsilon3/epsilon4 participants showed lower gray matter density
than the epsilon3/epsilon3 participants in right medial temporal and bilateral
frontotemporal regions as well as other areas. There were no regions in which
epsilon3/epsilon4 participants showed higher gray matter density than
epsilon3/epsilon3 participants. CONCLUSIONS: Regionally reduced gray matter
density is detectable in cognitively intact adults with a single copy of the APOE
epsilon4 allele.
PMID- 17030757
TI - Dopamine agonists and cardiac valvulopathy in Parkinson disease: a case-control
study.
AB - OBJECTIVE: To determine the frequency of cardiac valvulopathy in patients with
Parkinson disease (PD) treated with or without dopamine agonists. METHODS: We
obtained transthoracic echocardiography and EKG in 210 consecutive patients with
PD admitted to our hospital between September 2004 and September 2005. We
analyzed the frequency according to the type of dopamine agonist. A case-control
design was adopted with dopamine agonist nontreated group as the reference group,
and multiple logistic regression analysis was conducted considering age, sex, and
duration of illness to examine the relationships between each dopamine agonist
and the presence of valvular abnormalities. RESULTS: The frequency of
valvulopathy was significantly higher in the cabergoline-treated group (68.8%,
11/16; affected patients/total) than in the dopamine agonist nontreated control
group (17.6%, 15/85). The frequency was not different between the pergolide group
(28.8%, 19/66) and the pramipexole group (25%, 4/16). The adjusted odds ratio was
significantly higher in the cabergoline group (12.96, 95% CI = 3.59 to 46.85),
compared with the pergolide group (2.18, 95% CI = 0.90 to 5.30) and pramipexole
group (1.62, 95% CI = 0.45 to 5.87). The mean daily dose was 3.8 mg for
cabergoline, 1.4 mg for pergolide, and 1.7 mg for pramipexole. The cumulative
dose and treatment duration of cabergoline in the valvulopathy subgroup were
significantly higher than in the nonvalvulopathy subgroup. CONCLUSION: The
frequency of valvulopathy was significantly increased in the cabergoline group.
Our results indicate that high cumulative dose and long-term treatment with
cabergoline are risk factors for valvulopathy in patients with Parkinson disease.
PMID- 17030758
TI - Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of
infancy.
AB - OBJECTIVE: To identify cryptic chromosomal deletions involving SCN1A in patients
with severe myoclonic epilepsy of infancy (SMEI). METHODS: Thirty-nine patients
with SMEI and without SCN1A point mutations and their parents were typed with 14
intragenic SCN1A polymorphisms to identify hemizygosity. The parental origin and
the extent of genomic deletions were determined by fluorescence in situ
hybridization analysis using genomic clones encompassing chromosome 2q24.3-q31.1.
Deletion breakpoints were more finely mapped by typing single-nucleotide
polymorphisms and microsatellite markers. RESULTS: We identified three patients
with SMEI who had genomic deletions encompassing the SCN1A locus. Deletion size
was between 607 kb and 4.7 Mb. Deletions originated de novo from paternal
chromosome in all subjects. One patient had central precocious puberty and
palatoschisis. Genotype-phenotype correlations suggest that these clinical
features are due to genes centromeric to SCN1A. CONCLUSIONS: Patients with severe
myoclonic epilepsy of infancy (SMEI) lacking SCN1A point mutations should be
investigated for cryptic chromosomal deletions involving SCN1A. Clinical features
other than epilepsy could be associated with SMEI as a consequence of deletions
in contiguous genes.
PMID- 17030759
TI - The contactin 4 gene locus at 3p26 is a candidate gene of SCA16.
AB - OBJECTIVE: To identify of the gene responsible for the onset of spinocerebellar
ataxia type 16 (SCA16). METHODS: We reanalyzed the linkage of the original
Japanese pedigree using updated information, including three additional subjects.
We then screened all exons located in the critical region. RESULTS: We reassigned
the locus of SCA16 to 3p26.2-pter (maximum logarithm-of-odds score = 5.177) and
identified only one point mutation (4,256C-->T) in the 3' untranslated region of
the contactin 4 gene (CNTN4) on chromosome 3p26.2-26.3, which cosegregated with
the disease. This mutation was not detected in 520 control subjects; moreover, we
revised the phenotype of SCA16 from pure to complicated SCA. CONCLUSION: The
contactin 4 gene (CNTN4) is associated with cerebellar degeneration in
spinocerebellar ataxia type 16. Additional studies are necessary to prove 4,256C-
>T to be a causative mutation.
PMID- 17030760
TI - Cerebellar limb tremor and inferior olivary hypertrophy.
PMID- 17030761
TI - Clinical features associated with impulse control disorders in Parkinson disease.
AB - In patients with Parkinson disease (PD), impulse control disorders (ICDs) such as
hypersexuality and pathologic gambling and shopping can be devastating
complications of antiparkinsonian treatment. To improve their detection, we
investigated clinical features associated with ICDs. Subjects were participants
in a longitudinal study of PD. ICDs were associated with use of dopamine agonists
and depressed mood, disinhibition, irritability, and appetite disturbance.
PMID- 17030762
TI - Creatine supplementation in Parkinson disease: a placebo-controlled randomized
pilot trial.
AB - Mitochondrial dysfunction plays a major role in the pathogenesis of Parkinson
disease (PD). Creatine (Cr) is an ergogenic compound that exerts neuroprotective
effects in animal models of PD. We conducted a 2-year placebo-controlled
randomized clinical trial on the effect of Cr in 60 patients with PD. Cr improved
patient mood and led to a smaller dose increase of dopaminergic therapy but had
no effect on overall Unified Parkinson's Disease Rating Scale scores or dopamine
transporter SPECT.
PMID- 17030763
TI - Speech and language delay are early manifestations of juvenile-onset Huntington
disease.
AB - The neurocognitive features of juvenile-onset Huntington disease (HD) are not
well understood. We present three patients with onset of HD symptoms before age
10 years in whom speech delay was the first symptom. Speech delay predated motor
symptoms by at least 2 years, and language function was consistently impaired on
formal testing. Screening for speech delay is particularly important in children
with a family history of HD.
PMID- 17030764
TI - Effect of donepezil on motor and cognitive function in Huntington disease.
AB - Striatal cholinergic dysfunction may be important in Huntington disease (HD). We
studied whether donepezil improves chorea, cognition, and quality of life (QoL)
in HD. Thirty patients were randomly assigned to treatment with donepezil or
placebo. At the doses studied, donepezil did not improve chorea, cognition, or
QoL. Adverse events were similar between both groups. Based on this small sample
study, donepezil was not an effective treatment for HD.
PMID- 17030765
TI - Progression of warfarin-associated intracerebral hemorrhage after INR
normalization with FFP.
AB - To identify hematoma progression in patients with warfarin-associated
intracerebral hemorrhage (ICH) despite international normalized ratio (INR)
normalization with fresh-frozen plasma (FFP), we reviewed 45 patients with
warfarin-associated ICH given FFP. The median time for door to INR normalization
was 30 hours (14 to 49.5), with 4 patients' hematomas enlarging after INR
normalization. FFP is associated with substantial time delay to actual
administration and pulmonary edema and may not prevent progression of ICH despite
INR normalization.
PMID- 17030766
TI - Warfarin vs aspirin for symptomatic intracranial stenosis: subgroup analyses from
WASID.
AB - The WASID trial showed no advantage of warfarin over aspirin for preventing the
primary endpoint of ischemic stroke, brain hemorrhage, or vascular death. In
analyses of selected subgroups, there was no definite benefit from warfarin.
Warfarin reduced the risk of the primary endpoint among patients with basilar
artery stenosis, but there was no reduction in stroke in the basilar artery
territory or benefit for vertebral artery stenosis or posterior circulation
disease in general.
PMID- 17030767
TI - Predictors of hospital length of stay and cost in patients with intracerebral
hemorrhage.
AB - We used the 2002 Healthcare Cost and Utilization Project Nationwide Inpatient
Sample to assess hospital length of stay (LOS) and cost among adults with a
principal diagnosis of intracerebral hemorrhage (n = 13,239). Sixty-nine percent
of patients were aged > or =65 years, and 31% died during hospitalization. Mean
LOS (cost) was 7.7 days (15,256 dollars) (survivors: 9.6 days, 17,442 dollars).
Patient, hospital, and payer characteristics accounted for 69.1% of variation in
cost per discharge.
PMID- 17030768
TI - Gender differences in self-report of recovery after stroke: the Northern
Manhattan Study.
AB - We compared subjective responses to simple questions after stroke with
interviewer-assessed stroke outcome measures. Among those in the highest
functional category, women were more likely to report incomplete recovery and
greater need for help than men. Among these women, depressed mood was associated
with a response of a need for help despite a good functional recovery. Self
reported responses in stroke outcome assessments require further validation by
gender and may need to consider the confounding effects of depression.
PMID- 17030769
TI - What's inside the art? The influence of frontotemporal dementia in art
production.
AB - We evaluated the productions of an artist with frontotemporal lobar degeneration
from before dementia onset until she was fully symptomatic. We noted an
improvement of technique that might be related to sparing and disinhibition of
the right posterior neocortex. There was a reduction of closure (completeness of
the painting), possibly induced by impersistence and a decrease in evocative
impact that might be explained by frontal and anterotemporal-limbic dysfunction.
PMID- 17030770
TI - Elevated CSF free kappa light chains correlate with disability prognosis in
multiple sclerosis.
AB - Elevated CSF free kappa light chains (FKLCs) may predict disability in multiple
sclerosis (MS). We reviewed records of 57 patients with MS with 15-year median
follow-up for correlations of disability and CSF FKLCs. Levels > or = 1.53
microg/mL predicted progression to need for ambulatory assistance during follow
up (specificity 87.5%, positive predictive value 88.9%) or within 10 years
(specificity 78.6%, positive predictive value 66.7%).
PMID- 17030771
TI - Liver test abnormalities in multiple sclerosis: findings from placebo-treated
patients.
AB - The risk of an abnormal liver test in 813 patients with multiple sclerosis or
clinically isolated syndrome enrolled in placebo arms of clinical trials was
greater than expected for alanine aminotransferase (ALT) (relative risk [RR] 3.7;
95% CI: 2.3 to 6.0) and aspartate aminotransferase (AST) (RR 2.2; 95% CI: 1.3 to
3.6), although not alkaline phosphatase (AP) or total bilirubin, at first
presentation. Abnormal test results were associated with higher body mass index
(ALT only), male gender (ALT only), and a relapsing-remitting (vs secondary
progressive) course (ALT and AST only).
PMID- 17030772
TI - Development and evaluation of a self-administered version of the ALSFRS-R.
AB - We evaluated the reliability and sensitivity to change over time of a newly
developed self-administered version of the ALS functional rating scale-revised
(ALSFRS-R) in 60 consecutive patients from an ALS clinic. The self-administered
ALSFRS-R showed excellent reliability (intraclass correlation = 0.93, 95% CI: 088
to 0.96) and similar sensitivity to change over time vs the standard evaluator
administered ALSFRS-R.
PMID- 17030773
TI - Valproate effects on kinetics of lamotrigine in pregnancy and treatment with oral
contraceptives.
AB - In eight women treated with lamotrigine monotherapy, the lamotrigine dose/plasma
concentration (D/C) ratio increased by 295% from baseline outside pregnancy to
midgestation, whereas in six women treated with lamotrigine in combination with
valproate, the increase was only 60%. No difference in lamotrigine D/C ratio was
found between users and nonusers of oral contraceptives comedicated with
valproate. Valproate seems to reduce the induction of lamotrigine metabolism
associated with pregnancy or use of contraceptives.
PMID- 17030774
TI - Clinical features of chromosome 16q22.1 linked autosomal dominant cerebellar
ataxia in Japanese.
AB - Chromosome 16q22.1-linked autosomal dominant cerebellar ataxia (16q-ADCA) is
strongly associated with a substitution in the puratrophin-1 gene. This locus
overlaps with spinocerebellar ataxia type 4 (SCA4) which shows ataxia with
prominent sensory axonal neuropathy. We found that 16q-ADCA is a common ADCA
subtype in the Tohoku District of Japan. The clinical feature of Japanese 16q
ADCA is characterized as late-onset pure cerebellar ataxia.
PMID- 17030775
TI - Metastases to the pineal gland.
AB - We identified 10 patients with symptomatic metastases to the pineal gland. We
present the clinical and radiographic findings in this syndrome. Leptomeningeal
metastases occur frequently and are a poor prognostic factor. In all cases, the
primary cancer was clinically silent, either in remission (six cases) or
previously undiagnosed (four cases). Hence, metastatic disease, albeit uncommon,
should be considered in the differential diagnosis of pineal tumors.
PMID- 17030776
TI - Homonymous hemianopsia complicating treatment of postoperative epistaxis.
PMID- 17030777
TI - Crossed aphasia elicited by direct cortical stimulation.
PMID- 17030778
TI - Effect of topiramate on cognition in obese children.
PMID- 17030779
TI - Improvement with corticosteroids and azathioprine in GAD65-associated cerebellar
ataxia.
PMID- 17030780
TI - ACE activity in CSF of patients with mild cognitive impairment and Alzheimer
disease.
PMID- 17030781
TI - Action myoclonus-renal failure syndrome: a cause for worsening tremor in young
adults.
PMID- 17030783
TI - A randomized study of two interferon-beta treatments in relapsing-remitting
multiple sclerosis.
PMID- 17030784
TI - Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled
clinical trial.
PMID- 17030785
TI - Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS.
PMID- 17030786
TI - DNA mismatch-specific targeting and hypersensitivity of mismatch-repair-deficient
cells to bulky rhodium(III) intercalators.
AB - Mismatch repair (MMR) is critical to maintaining the integrity of the genome, and
deficiencies in MMR are correlated with cancerous transformations. Bulky rhodium
intercalators target DNA base mismatches with high specificity. Here we describe
the application of bulky rhodium intercalators to inhibit cellular proliferation
differentially in MMR-deficient cells compared with cells that are MMR
proficient. Preferential inhibition by the rhodium complexes associated with MMR
deficiency is seen both in a human colon cancer cell line and in normal mouse
fibroblast cells; the inhibition of cellular proliferation depends strictly on
the MMR deficiency of the cell. Furthermore, our assay of cellular proliferation
is found to correlate with DNA mismatch targeting by the bulky
metallointercalators. It is the Delta-isomer that is active both in targeting
base mismatches and in inhibiting DNA synthesis. Additionally, the rhodium
intercalators promote strand cleavage at the mismatch site with photoactivation,
and we observe that the cellular response is enhanced with photoactivation.
Targeting DNA mismatches may therefore provide a cell-selective strategy for
chemotherapeutic design.
PMID- 17030787
TI - Programming social, cognitive, and neuroendocrine development by early exposure
to novelty.
AB - Mildly stressful early life experiences can potentially impact a broad range of
social, cognitive, and physiological functions in humans, nonhuman primates, and
rodents. Recent rodent studies favor a maternal-mediation hypothesis that
considers maternal-care differences induced by neonatal stimulation as the cause
of individual differences in offspring development. Using neonatal novelty
exposure, a neonatal stimulation paradigm that dissociates maternal individual
differences from a direct stimulation effect on the offspring, we investigated
the effect of early exposures to novelty on a diverse range of psychological
functions using several assessment paradigms. Pups that received brief neonatal
novelty exposures away from the home environment showed enhancement in spatial
working memory, social competition, and corticosterone response to surprise
during adulthood compared with their home-staying siblings. These functional
enhancements in novelty-exposed rats occurred despite evidence that maternal care
was directed preferentially toward home-staying instead of novelty-exposed pups,
indicating that greater maternal care is neither necessary nor sufficient for
these early stimulation-induced functional enhancements. We suggest a unifying
maternal-modulation hypothesis, which distinguishes itself from the maternal
mediation hypothesis in that (i) neonatal stimulation can have direct effects on
pups, cumulatively leading to long-term improvement in adult offspring; and (ii)
maternal behavior can attenuate or potentiate these effects, thereby decreasing
or increasing this long-term functional improvement.
PMID- 17030788
TI - Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene
expression in skeletal muscle: Role of PGC-1alpha.
AB - Previous investigations show that intracerebroventricular administration of a
potent inhibitor of fatty acid synthase, C75, increases the level of its
substrate, malonyl-CoA, in the hypothalamus. The "malonyl-CoA signal" is rapidly
transmitted to skeletal muscle by the sympathetic nervous system, increasing
fatty acid oxidation, uncoupling protein-3 (UCP3) expression, and thus, energy
expenditure. Here, we show that intracerebroventricular or intraperitoneal
administration of C75 increases the number of mitochondria in white and red
(soleus) skeletal muscle. Consistent with signal transmission from the
hypothalamus by the sympathetic nervous system, centrally administered C75
rapidly (< or =2 h) up-regulated the expression (in skeletal muscle) of the beta
adrenergic signaling molecules, i.e., norepinephrine, beta3-adrenergic receptor,
and cAMP; the transcriptional regulators peroxisomal proliferator activator
regulator gamma coactivator 1alpha (PGC-1alpha) and estrogen receptor-related
receptor alpha (ERRalpha); and the expression of key oxidative mitochondrial
enzymes, including pyruvate dehydrogenase kinase, medium-chain length fatty acyl
CoA dehydrogenase, ubiquinone-cytochrome c reductase, cytochrome oxidase, as well
as ATP synthase and UCP3. The role of PGC-1alpha in mediating these responses in
muscle was assessed with C2C12 myocytes in cell culture. Consistent with the in
vivo response, adenovirus-directed expression of PGC-1alpha in C2C12 muscle cells
provoked the phosphorylation/inactivation and reduced expression of acetyl-CoA
carboxylase 2, causing a reduction of the malonyl-CoA concentration. These
effects, coupled with an increased carnitine palmitoyltransferase 1b, led to
increased fatty acid oxidation. PGC-1alpha also increased the expression of
ERRalpha, PPARalpha, and enzymes that support mitochondrial fatty acid oxidation,
ATP synthesis, and thermogenesis, apparently mediated by an increased expression
of UCP3.
PMID- 17030790
TI - Mathematical analysis of locomotor behavior by mice in a radial maze.
AB - We investigated the effects of beta-estradiol on the locomotor behavior of female
mice in a radial maze. Data comprising the total distance traveled during each
arm entry were obtained from video records of six consecutive daily recording
sessions. Distributions of these data were bimodal for both ovariectomized
control and beta-estradiol-treated ovariectomized subjects. Data were fit with
the sum of two gamma probability distributions. Three parameters of the analytic
fits were useful for quantifying the effect of beta-estradiol on locomotor
behavior: (i) the sampling distance (median of the total distance traveled during
each arm entry in the short-distance peak of a bimodal distribution), (ii) the
committed distance (median of the total per-arm-entry distance traveled in the
long-distance peak), and (iii) the partition distance (distance represented by
the minimum between the two peaks). Analysis showed that for sampling-distance
arm entries beta-estradiol typically had little if any significant effect on
female locomotor behavior, whereas it significantly increased the total distance
traveled during committed-distance arm entries on the first 2 days of exposure to
the empty maze. beta-Estradiol also increased the ability of females to
discriminate between empty maze arms and arms that contained intact or castrated
male mice and partially prevented loss of this capacity after removal of the
males.
PMID- 17030789
TI - Increased susceptibility to bacterial superinfection as a consequence of innate
antiviral responses.
AB - The reason why severe localized or systemic virus infections enhance and
aggravate bacterial superinfection is poorly understood. Here we show that virus
induced IFN type I caused apoptosis in bone marrow granulocytes, drastically
reduced granulocyte infiltrates at the site of bacterial superinfection, caused
up to 1,000-fold higher bacterial titers in solid organs, and increased disease
susceptibility. The finding that the innate antiviral immune response reduces the
antibacterial granulocyte defense offers an explanation for enhanced
susceptibility to bacterial superinfection during viral disease.
PMID- 17030791
TI - G protein-coupled receptors sense fluid shear stress in endothelial cells.
AB - Hemodynamic shear stress stimulates a number of intracellular events that both
regulate vessel structure and influence development of vascular pathologies. The
precise molecular mechanisms by which endothelial cells transduce this mechanical
stimulus into intracellular biochemical response have not been established. Here,
we show that mechanical perturbation of the plasma membrane leads to ligand
independent conformational transitions in a G protein-coupled receptor (GPCR). By
using time-resolved fluorescence microscopy and GPCR conformation-sensitive FRET
we found that stimulation of endothelial cells with fluid shear stress, hypotonic
stress, or membrane fluidizing agent leads to a significant increase in activity
of bradykinin B2 GPCR in endothelial cells. The GPCR conformational dynamics was
detected by monitoring redistribution of GPCRs between inactive and active
conformations in a single endothelial cell under fluid shear stress in real time.
We show that this response can be blocked by a B(2)-selective antagonist. Our
data demonstrate that changes in cell membrane tension and membrane fluidity
affect conformational dynamics of GPCRs. Therefore, we suggest that GPCRs are
involved in mediating primary mechanochemical signal transduction in endothelial
cells. We anticipate our experiments to be a starting point for more
sophisticated studies of the effects of changes in lipid bilayer environment on
GPCR conformational dynamics. Furthermore, because GPCRs are a major target of
drug development, a detailed characterization of mechanochemical signaling via
the GPCR pathway will be relevant for the development of new antiatherosclerosis
drugs.
PMID- 17030792
TI - Protein folding is slaved to solvent motions.
AB - Proteins, the workhorses of living systems, are constructed from chains of amino
acids, which are synthesized in the cell based on the instructions of the genetic
code and then folded into working proteins. The time for folding varies from
microseconds to hours. What controls the folding rate is hotly debated. We
postulate here that folding has the same temperature dependence as the alpha
fluctuations in the bulk solvent but is much slower. We call this behavior
slaving. Slaving has been observed in folded proteins: Large-scale protein
motions follow the solvent fluctuations with rate coefficient k(alpha) but can be
slower by a large factor. Slowing occurs because large-scale motions proceed in
many small steps, each determined by k(alpha). If conformational motions of
folded proteins are slaved, so a fortiori must be the motions during folding. The
unfolded protein makes a Brownian walk in the conformational space to the folded
structure, with each step controlled by k(alpha). Because the number of
conformational substates in the unfolded protein is extremely large, the folding
rate coefficient, k(f), is much smaller than k(alpha). The slaving model implies
that the activation enthalpy of folding is dominated by the solvent, whereas the
number of steps n(f) = k(alpha)/k(f) is controlled by the number of accessible
substates in the unfolded protein and the solvent. Proteins, however, undergo not
only alpha- but also beta-fluctuations. These additional fluctuations are local
protein motions that are essentially independent of the bulk solvent fluctuations
and may be relevant at late stages of folding.
PMID- 17030793
TI - Comparative genomics of the lactic acid bacteria.
AB - Lactic acid-producing bacteria are associated with various plant and animal
niches and play a key role in the production of fermented foods and beverages. We
report nine genome sequences representing the phylogenetic and functional
diversity of these bacteria. The small genomes of lactic acid bacteria encode a
broad repertoire of transporters for efficient carbon and nitrogen acquisition
from the nutritionally rich environments they inhabit and reflect a limited range
of biosynthetic capabilities that indicate both prototrophic and auxotrophic
strains. Phylogenetic analyses, comparison of gene content across the group, and
reconstruction of ancestral gene sets indicate a combination of extensive gene
loss and key gene acquisitions via horizontal gene transfer during the
coevolution of lactic acid bacteria with their habitats.
PMID- 17030794
TI - The complete genome of Rhodococcus sp. RHA1 provides insights into a catabolic
powerhouse.
AB - Rhodococcus sp. RHA1 (RHA1) is a potent polychlorinated biphenyl-degrading soil
actinomycete that catabolizes a wide range of compounds and represents a genus of
considerable industrial interest. RHA1 has one of the largest bacterial genomes
sequenced to date, comprising 9,702,737 bp (67% G+C) arranged in a linear
chromosome and three linear plasmids. A targeted insertion methodology was
developed to determine the telomeric sequences. RHA1's 9,145 predicted protein
encoding genes are exceptionally rich in oxygenases (203) and ligases (192). Many
of the oxygenases occur in the numerous pathways predicted to degrade aromatic
compounds (30) or steroids (4). RHA1 also contains 24 nonribosomal peptide
synthase genes, six of which exceed 25 kbp, and seven polyketide synthase genes,
providing evidence that rhodococci harbor an extensive secondary metabolism.
Among sequenced genomes, RHA1 is most similar to those of nocardial and
mycobacterial strains. The genome contains few recent gene duplications.
Moreover, three different analyses indicate that RHA1 has acquired fewer genes by
recent horizontal transfer than most bacteria characterized to date and far fewer
than Burkholderia xenovorans LB400, whose genome size and catabolic versatility
rival those of RHA1. RHA1 and LB400 thus appear to demonstrate that ecologically
similar bacteria can evolve large genomes by different means. Overall, RHA1
appears to have evolved to simultaneously catabolize a diverse range of plant
derived compounds in an O(2)-rich environment. In addition to establishing RHA1
as an important model for studying actinomycete physiology, this study provides
critical insights that facilitate the exploitation of these industrially
important microorganisms.
PMID- 17030795
TI - Compartmental signal modulation: Endosomal phosphatidylinositol 3-phosphate
controls endosome morphology and selective cargo sorting.
AB - It is increasingly recognized that the compartmental organization of signaling
processes has a profound influence on cellular behavior. However, our inability
to influence these compartmental events in a spatially restricted and acute
manner limits our understanding of causation. To determine whether local
compartmental loss of a phosphoinositide disrupts the normal traffic of specific
cargoes through endosomes, we developed the use of a regulated dimerization
device, here designed to compartmentally modify the phosphoinositide content of
Rab5-positive endosomes. This modification is effected through the specific
regulated recruitment of the 3-phosphatase myotubularin to endosomal membranes in
intact cells. The selective manipulation of endosomal phosphatidylinositols (PIs)
demonstrates that it is the phosphatidylinositol 3-phosphate (PtdIns3P) or its
metabolite PtdIns(3,5)P2 within this compartment that determines the normal
maturation of the endosomal compartment and the flux of receptors through it. On
local loss of PtdIns3P/PtdIns(3,5)P2, the endosomal compartment itself fails to
continue its normal maturation process, leading to the microtubule-dependent
tubularization of the endosomal network. Furthermore, it is shown that endosomal
PtdIns3P/PtdIns(3,5)P2 is necessary for transferrin receptor traffic through this
compartment while having an effect on EGF receptor (EGFR) entry into and sorting
from this endosome compartment. The ability to acutely and selectively influence
compartmental behavior as exemplified here for endomsomes clearly illustrates the
power of the approach used to dissect the role of localized signals and events.
PMID- 17030796
TI - Acrolein is a major cigarette-related lung cancer agent: Preferential binding at
p53 mutational hotspots and inhibition of DNA repair.
AB - The tumor suppressor gene p53 is frequently mutated in cigarette smoke (CS)
related lung cancer. The p53 binding pattern of carcinogenic polycyclic aromatic
hydrocarbons (PAHs) found in CS coincides with the p53 mutational pattern found
in lung cancer, and PAHs have thus been considered to be major culprits for lung
cancer. However, compared with other carcinogenic compounds, such as aldehydes,
the amount of PAHs in CS is minute. Acrolein (Acr) is abundant in CS, and it can
directly adduct DNA. Acr-DNA adducts, similar to PAH-DNA adducts, induce
predominantly G-to-T transversions in human cells. These findings raise the
question of whether Acr-DNA adducts are responsible for p53 mutations in CS
related lung cancer. To determine the role of Acr-DNA adducts in p53 mutagenesis
in CS-related lung cancer we mapped the distribution of Acr-DNA adducts at the
sequence level in the p53 gene of lung cells using the UvrABC incision method in
combination with ligation-mediated PCR. We found that the Acr-DNA binding pattern
is similar to the p53 mutational pattern in human lung cancer. Acr preferentially
binds at CpG sites, and this enhancement of binding is due to cytosine
methylation at these sequences. Furthermore, we found that Acr can greatly reduce
the DNA repair capacity for damage induced by benzo[a]pyrene diol epoxide.
Together these results suggest that Acr is a major etiological agent for CS
related lung cancer and that it contributes to lung carcinogenesis through two
detrimental effects: DNA damage and inhibition of DNA repair.
PMID- 17030797
TI - Burkholderia xenovorans LB400 harbors a multi-replicon, 9.73-Mbp genome shaped
for versatility.
AB - Burkholderia xenovorans LB400 (LB400), a well studied, effective polychlorinated
biphenyl-degrader, has one of the two largest known bacterial genomes and is the
first nonpathogenic Burkholderia isolate sequenced. From an evolutionary
perspective, we find significant differences in functional specialization between
the three replicons of LB400, as well as a more relaxed selective pressure for
genes located on the two smaller vs. the largest replicon. High genomic
plasticity, diversity, and specialization within the Burkholderia genus are
exemplified by the conservation of only 44% of the genes between LB400 and
Burkholderia cepacia complex strain 383. Even among four B. xenovorans strains,
genome size varies from 7.4 to 9.73 Mbp. The latter is largely explained by our
findings that >20% of the LB400 sequence was recently acquired by means of
lateral gene transfer. Although a range of genetic factors associated with in
vivo survival and intercellular interactions are present, these genetic factors
are likely related to niche breadth rather than determinants of pathogenicity.
The presence of at least eleven "central aromatic" and twenty "peripheral
aromatic" pathways in LB400, among the highest in any sequenced bacterial genome,
supports this hypothesis. Finally, in addition to the experimentally observed
redundancy in benzoate degradation and formaldehyde oxidation pathways, the fact
that 17.6% of proteins have a better LB400 paralog than an ortholog in a
different genome highlights the importance of gene duplication and repeated
acquirement, which, coupled with their divergence, raises questions regarding the
role of paralogs and potential functional redundancies in large-genome microbes.
PMID- 17030798
TI - Methionine catabolism in Arabidopsis cells is initiated by a gamma-cleavage
process and leads to S-methylcysteine and isoleucine syntheses.
AB - Despite recent progress in elucidating the regulation of methionine (Met)
synthesis, little is known about the catabolism of this amino acid in plants. In
this article, we present several lines of evidence indicating that the cleavage
of Met catalyzed by Met gamma-lyase is the first step in this process. First, we
cloned an Arabidopsis cDNA coding a functional Met gamma-lyase (AtMGL), a
cytosolic enzyme catalyzing the conversion of Met into methanethiol, alpha
ketobutyrate, and ammonia. AtMGL is present in all of the Arabidopsis organs and
tissues analyzed, except in quiescent dry mature seeds, thus suggesting that
AtMGL is involved in the regulation of Met homeostasis in various situations.
Also, we demonstrated that the expression of AtMGL was induced in Arabidopsis
cells in response to high Met levels, probably to bypass the elevated Km of the
enzyme for Met. Second, [13C]-NMR profiling of Arabidopsis cells fed with
[13C]Met allowed us to identify labeled S-adenosylmethionine, S-methylmethionine,
S-methylcysteine (SMC), and isoleucine (Ile). The unexpected production of SMC
and Ile was directly associated to the function of Met gamma-lyase. Indeed, we
showed that part of the methanethiol produced during Met cleavage could react
with an activated form of serine to produce SMC. The second product of Met
cleavage, alpha-ketobutyrate, entered the pathway of Ile synthesis in plastids.
Together, these data indicate that Met catabolism in Arabidopsis cells is
initiated by a gamma-cleavage process and can result in the formation of the
essential amino acid Ile and a potential storage form for sulfide or methyl
groups, SMC.
PMID- 17030799
TI - Cell-surface heparan sulfate proteoglycans are essential components of the
unconventional export machinery of FGF-2.
AB - FGF-2 is an unconventionally secreted lectin that transmits proangiogenic signals
through a ternary complex with high-affinity FGF receptors and heparan sulfate
proteoglycans (HSPGs). Although FGF-2 signal transduction is understood in great
detail, its mechanism of release from cells, which is independent of the
classical secretory pathway, remains elusive. To test the hypothesis that FGF-2
secretion is linked to its cell-surface ligands, we studied FGF-2 release using
mutants defective for HSPG binding and cells with impaired HSPG biosynthesis.
Here, we report that a functional interaction between FGF-2 and HSPGs is required
for net export of FGF-2 from mammalian cells. FGF-2 release requires
extracellular, membrane-proximal HSPGs. We propose that extracellular HSPGs form
a molecular trap that drives FGF-2 translocation across the plasma membrane.
PMID- 17030800
TI - Pseudomonas aeruginosa type III-secreted toxin ExoT inhibits host-cell division
by targeting cytokinesis at multiple steps.
AB - Pseudomonas aeruginosa is an opportunistic pathogen that requires preexisiting
epithelial injury to cause acute infections. We report that P. aeruginosa
inhibits mammalian cytokinesis in a type III secretion system and exotoxin T
(ExoT)-dependent manner. ExoT is a bifunctional type III secretion system
effector protein that contains an N-terminal GTPase-activating protein domain and
a C-terminal ADP-ribosyl transferase domain. Each of its domains inhibits
cytokinesis in a kinetically, morphologically, and mechanistically distinct
manner. The GTPase-activating protein-mediated inhibition of cytokinesis occurs
early, likely as a consequence of its inhibitory effect on RhoA. The ADP-ribosyl
transferase domain inhibits late steps of cytokinesis by blocking syntaxin-2
localization to the midbody, an event essential for completion of cytokinesis.
These findings provide an example of a bacterial pathogen targeting cytokinesis.
PMID- 17030801
TI - Dual function of an Arabidopsis transcription factor DREB2A in water-stress
responsive and heat-stress-responsive gene expression.
AB - Transcription factor DREB2A interacts with a cis-acting dehydration-responsive
element (DRE) sequence and activates expression of downstream genes involved in
drought- and salt-stress response in Arabidopsis thaliana. Intact DREB2A
expression does not activate downstream genes under normal growth conditions. A
negative regulatory domain exists in the central region of DREB2A, and deletion
of this region transforms DREB2A to a constitutive active form (DREB2A CA). We
carried out microarray analysis of transgenic Arabidopsis-overexpressing DREB2A
CA and found that the overexpression of DREB2A CA induces not only drought- and
salt-responsive genes but also heat-shock (HS)-related genes. Moreover, we found
that transient induction of the DREB2A occurs rapidly by HS stress, and that the
sGFP-DREB2A protein accumulates in nuclei of HS-stressed cells. DREB2A up
regulated genes were classified into three groups based on their expression
patterns: genes induced by HS, genes induced by drought stress, and genes induced
by both HS and drought stress. DREB2A up-regulated genes were down-regulated in
DREB2A knockout mutants under stress conditions. Thermotolerance was
significantly increased in plants overexpressing DREB2A CA and decreased in
DREB2A knockout plants. Collectively, these results indicate that DREB2A
functions in both water and HS-stress responses.
PMID- 17030802
TI - Cell-free formation of misfolded prion protein with authentic prion infectivity.
AB - Prion propagation has been modeled in vitro; however, the low infectious titer of
PrP(Sc) thus generated has cast doubt on the "protein-only" hypothesis. Here we
show that prion delivery on suitable nitrocellulose carrier particles abrogates
the apparent dissociation of PrP(Sc) and infectivity. Misfolded prion protein
generated by protein misfolding cyclic amplification is as infectious as
authentic brain-derived PrP(Sc) provided that confounding effects related to
differences in the size distribution of prion protein aggregates generated in
vitro and consecutive differences in regard to biological clearance are
abolished.
PMID- 17030803
TI - Combinatorially selected defense peptides protect plant roots from pathogen
infection.
AB - Agricultural productivity and sustainability are continually challenged by
emerging and indigenous pathogens. Currently, many pathogens can be combatted
only with biocides or environmentally dangerous fumigants. Here, we report a
rapid and pathogen-specific strategy to reduce infection by organisms that target
plant roots. Combinatorially selected defense peptides, previously shown to
effect premature encystment of Phytophthora capsici zoospores, were fused to
maize cytokinin oxidase/dehydrogenase as a display scaffold. When expressed in
tomato roots, the peptide-scaffold constructs were secreted and accumulated to
sufficient concentrations in the rhizosphere to induce zoospore encystment and
thereby deter taxis to the root surface. Pathogen infection was significantly
inhibited in roots expressing bioactive peptides fused to the maize cytokinin
oxidase/dehydrogenase scaffold. This peptide-delivery technology is broadly
applicable for rapid development of plant defense attributes against plant
pathogens.
PMID- 17030804
TI - Structural basis for Rab11-dependent membrane recruitment of a family of Rab11
interacting protein 3 (FIP3)/Arfophilin-1.
AB - Family of Rab11-interacting protein (FIP)3/Arfophlin-1 and FIP4/Arfophilin-2 are
dual effectors for Rab11 and ADP ribosylation factor (ARF)5/ARF6, which are
involved in membrane delivery from recycling endosomes to the plasma membrane
during cytokinesis. Here, we define the distinct C-terminal binding regions of
FIP3 and FIP4 for Rab11 and ARF5/ARF6. Furthermore, we determined the crystal
structure of Rab11 in complex with the Rab11-binding domain (RBD) of FIP3. The
long amphiphilic alpha-helix of FIP3-RBD forms a parallel coiled-coil homodimer,
with two symmetric interfaces with two Rab11 molecules. The hydrophobic side of
the RBD helix is involved in homodimerization and mediates the interaction with
the Rab11 switch 1 region, whereas the opposite hydrophilic side interacts with
the Rab11 switch 2 and is the major factor contributing to the binding
specificity. The bivalent interaction of FIP3 with Rab11 at the C terminus allows
FIP3 to coordinately function with other binding partners, including ARFs.
PMID- 17030805
TI - A seven-helix coiled coil.
AB - Coiled-coil proteins contain a characteristic seven-residue sequence repeat whose
positions are designated a to g. The interacting surface between alpha-helices in
a classical coiled coil is formed by interspersing nonpolar side chains at the a
and d positions with hydrophilic residues at the flanking e and g positions. To
explore how the chemical nature of these core amino acids dictates the overall
coiled-coil architecture, we replaced all eight e and g residues in the GCN4
leucine zipper with nonpolar alanine side chains. Surprisingly, the alanine
containing mutant forms a stable alpha-helical heptamer in aqueous solution. The
1.25-A resolution crystal structure of the heptamer reveals a parallel seven
stranded coiled coil enclosing a large tubular channel with an unusual heptad
register shift between adjacent staggered helices. The overall geometry comprises
two interleaved hydrophobic helical screws of interacting cross-sectional a and d
layers that have not been seen before. Moreover, asparagines at the a positions
play an essential role in heptamer formation by participating in a set of buried
interhelix hydrogen bonds. These results demonstrate that heptad repeats
containing four hydrophobic positions can direct assembly of complex, higher
order coiled-coil structures with rich diversity for close packing of alpha
helices.
PMID- 17030806
TI - An 85-aa segment of the GB virus type C NS5A phosphoprotein inhibits HIV-1
replication in CD4+ Jurkat T cells.
AB - GB virus type C (GBV-C) is an apparently nonpathogenic virus that replicates in T
and B lymphocytes and is a common cause of persistent human infection. Among HIV
1-infected individuals, persistent coinfection with GBV-C is associated with
prolonged survival, and infection of blood mononuclear cells or CD4+ T cells with
GBV-C and HIV in vitro results in significantly reduced HIV-1 replication. To
date, the viral protein(s) that lead to HIV inhibition have not been identified.
The GBV-C nonstructural phosphoprotein (NS5A) is predicted to have pleotropic
effects on cells, including interactions with the IFN-induced dsRNA-activated
protein kinase (PKR). We studied GBV-C NS5A to determine whether it is involved
in inhibition of HIV replication. GBV-C NS5A protein from an isolate that was
cleared by IFN therapy did not inhibit PKR, whereas NS5A from an isolate that was
not cleared by IFN-inhibited PKR function in a yeast genetic system. Both of
these GBV-C NS5A proteins were expressed in a CD4+ T cell line (Jurkat), and both
induced a potent, dose-dependent inhibition of HIV-1 replication, thus the effect
was independent of PKR inhibition. NS5A induced the release of the chemokine SDF
1 and decreased surface expression of the HIV coreceptor CXCR4, potentially
explaining the HIV inhibition. Deletion mapping of the NS5A protein found that an
85-aa region between amino acids 152 and 237 inhibits HIV-1 replication. Thus,
GBV-C NS5A protein alters the cellular milieu necessary for HIV-1 replication and
may provide a previously undescribed therapeutic approach for anti-HIV therapy.
PMID- 17030807
TI - High-molecular-mass APOBEC3G complexes restrict Alu retrotransposition.
AB - APOBEC3G (A3G) and related deoxycytidine deaminases are potent intrinsic
antiretroviral factors. A3G is expressed either as an enzymatically active low
molecular-mass (LMM) form or as an enzymatically inactive high-molecular-mass
(HMM) ribonucleoprotein complex. Resting CD4 T cells exclusively express LMM A3G,
where it functions as a powerful postentry restriction factor for HIV-1.
Activation of CD4 T cells promotes the recruitment of LMM A3G into 5- to 15-MDa
HMM complexes whose function is unknown. Using tandem affinity purification
techniques coupled with MS, we identified Staufen-containing RNA-transporting
granules and Ro ribonucleoprotein complexes as specific components of HMM A3G
complexes. Analysis of RNAs in these complexes revealed Alu and small Y RNAs, two
of the most prominent nonautonomous mobile genetic elements in human cells. These
retroelement RNAs are recruited into Staufen-containing RNA-transporting granules
in the presence of A3G. Retrotransposition of Alu and hY RNAs depends on the
reverse transcriptase machinery provided by long interspersed nucleotide elements
1 (L1). We now show that A3G greatly inhibits L1-dependent retrotransposition of
marked Alu retroelements not by inhibiting L1 function but by sequestering Alu
RNAs in cytoplasmic HMM A3G complexes away from the nuclear L1 enzymatic
machinery. These findings identify nonautonomous Alu and hY retroelements as
natural cellular targets of A3G and highlight how different forms of A3G uniquely
protect cells from the threats posed by exogenous retroviruses (LMM A3G) and
endogenous retroelements (HMM A3G).
PMID- 17030808
TI - Human fronto-mesolimbic networks guide decisions about charitable donation.
AB - Humans often sacrifice material benefits to endorse or to oppose societal causes
based on moral beliefs. Charitable donation behavior, which has been the target
of recent experimental economics studies, is an outstanding contemporary
manifestation of this ability. Yet the neural bases of this unique aspect of
human altruism, which extends beyond interpersonal interactions, remain obscure.
In this article, we use functional magnetic resonance imaging while participants
anonymously donated to or opposed real charitable organizations related to major
societal causes. We show that the mesolimbic reward system is engaged by
donations in the same way as when monetary rewards are obtained. Furthermore,
medial orbitofrontal-subgenual and lateral orbitofrontal areas, which also play
key roles in more primitive mechanisms of social attachment and aversion,
specifically mediate decisions to donate or to oppose societal causes.
Remarkably, more anterior sectors of the prefrontal cortex are distinctively
recruited when altruistic choices prevail over selfish material interests.
PMID- 17030809
TI - Visual saliency and texture segregation without feature gradient.
AB - A central notion in the study of texture segregation is that of feature gradient
(or feature contrast). In orientation-based texture segregation, orientation
gradients have indeed played a fundamental role in explaining behavioral results.
Here, however, we show that general, smoothly varying, orientation-defined
textures (ODTs) exhibit striking perceptual singularities that are completely
unpredictable from orientation gradients. These singularities defy not only
popular texture segregation theories but also virtually all computational
segmentation methods, and they confound previous behavioral studies with smoothly
varying ODTs. We provide psychophysical evidence that perceptual singularities in
smooth ODTs are salient visual features consistent across observers and with
significant effect on the perception and segregation of oriented textures. We
further show that, although orientation gradients cannot predict them, perceptual
singularities in smooth ODTs emerge directly from, and can be spatially localized
by, two ODT curvatures. Given the traditional role of feature gradients in early
vision, the significance of these findings extends well beyond orientation-based
texture segregation to issues ranging from curve integration and fragment
grouping, through the perception of 3D shape, to the functional organization of
the primary visual cortex.
PMID- 17030810
TI - L-Kynurenine, an amino acid identified as a sex pheromone in the urine of
ovulated female masu salmon.
AB - Many animals employ sex pheromones to find mating partners during their
reproductive seasons. However, most sex pheromones of vertebrates remain to be
identified. Over the past 20 years, steroids and prostaglandins have been
identified as sex pheromones in several fishes. These pheromones are broadly
termed "hormonal pheromones" because they or their precursors act as hormones in
these fishes. Hitherto, no other type of sex pheromone has been unambiguously
identified in teleost fish. Here we report the identification of a "nonhormonal
pheromone" in teleost fish. The urine of the reproductively mature female masu
salmon (Oncorhynchus masou) contains a male-attracting pheromone. Bioassay-guided
fractionation yielded an active compound that was identical to L-kynurenine in
spectral and chromatographic properties. L-Kynurenine is a major metabolite of L
tryptophan in vertebrates. This pheromone elicits a male-specific behavior at
even picomolar concentrations; its electrophysiological threshold is 10(-14) M. L
Kynurenine is a reasonable substance for female masu salmon to advertise their
readiness for mating.
PMID- 17030811
TI - Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in
rats and humans.
AB - MENX is a recessive multiple endocrine neoplasia-like syndrome in the rat. The
tumor spectrum in MENX overlaps those of human multiple endocrine neoplasia (MEN)
types 1 and 2. We mapped the MenX locus to the distal part of rat chromosome 4,
excluding the homologs of the genes responsible for the MEN syndromes (RET and
MEN1) and syndromes with an endocrine tumor component (VHL and NF1). We report
the fine mapping of the disease locus and the identification of a homozygous
frameshift mutation in Cdkn1b, encoding the cyclin-dependent kinase inhibitor
p27(Kip1). As a consequence of the mutation, MENX-affected rats show dramatic
reduction in p27(Kip1) protein. We have identified a germ-line nonsense mutation
in the human CDKN1B gene in a MEN1 mutation-negative patient presenting with
pituitary and parathyroid tumors. Expanded pedigree analysis shows that the
mutation is associated with the development of an MEN1-like phenotype in multiple
generations. Our findings demonstrate that germ-line mutations in p27(Kip1) can
predispose to the development of multiple endocrine tumors in both rats and
humans.
PMID- 17030813
TI - MicroRNAs and osmotic regulation.
PMID- 17030814
TI - Angiopoietin-2 functions as an autocrine protective factor in stressed
endothelial cells.
AB - Angiopoietin (Ang)-2, a context-dependent agonist/antagonist for the vascular
specific Tie2 receptor, is highly expressed by endothelial cells at sites of
normal and pathologic angiogenesis. One prevailing model suggests that in these
settings, Ang-2 acts as an autocrine Tie2 blocker, inhibiting the stabilizing
influence of the Tie2 activator Ang-1, thereby promoting vascular remodeling.
However, the effects of endogenous Ang-2 on cells that are actively producing it
have not been studied in detail. Here, we demonstrate that Ang-2 expression is
rapidly induced in endothelial cells by the transcription factor FOXO1 after
inhibition of the phosphatidylinositol 3-kinase/Akt pathway. We employ RNAi and
blocking antibodies to show that in this setting, Ang-2 unexpectedly functions as
a Tie2 agonist, bolstering Akt activity so as to provide negative feedback on
FOXO1-regulated transcription and apoptosis. In addition, we show that Ang-2,
like Ang-1, activates Tie2/Akt signaling in vivo, thereby inhibiting the
expression of FOXO1 target genes. Consistent with a role for Ang-2 as a Tie2
activator, we demonstrate that Ang-2 inhibits vascular leak. Our data suggests a
model in which Ang-2 expression is induced in stressed endothelial cells, where
it acts as an autocrine Tie2 agonist and protective factor.
PMID- 17030815
TI - Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell
response to histone deacetylase inhibitor.
AB - There is a great need to develop better mechanism-based therapies for prostate
cancer. In this investigation, we studied four human prostate cancer cell lines,
LNCaP, DU145, LAPC4, and PC3, which differ in response to the histone deacetylase
inhibitor, suberoylanilide hydroxamic acid (vorinostat), a new anticancer drug.
Examining the role of intrinsic mitochondrial caspase-dependent apoptosis and
caspase-independent, reactive oxygen species (ROS) facilitated cell death, has
provided an understanding of mechanisms that may determine the varied response to
the histone deacetylase inhibitor. We found striking differences among these
cancer cells in constitutive expression and response to suberoylanilide
hydroxamic acid in levels of antiapoptotic and proapoptotic proteins,
mitochondria membrane integrity, activation of caspases, ROS accumulation, and
expression of thioredoxin, the major scavenger of ROS. Identifying these
differences can have predictive value in assessing therapeutic response and
identifying targets to enhance therapeutic efficacy.
PMID- 17030812
TI - The deepest divergences in land plants inferred from phylogenomic evidence.
AB - Phylogenetic relationships among the four major lineages of land plants
(liverworts, mosses, hornworts, and vascular plants) remain vigorously contested;
their resolution is essential to our understanding of the origin and early
evolution of land plants. We analyzed three different complementary data sets: a
multigene supermatrix, a genomic structural character matrix, and a chloroplast
genome sequence matrix, using maximum likelihood, maximum parsimony, and
compatibility methods. Analyses of all three data sets strongly supported
liverworts as the sister to all other land plants, and analyses of the multigene
and chloroplast genome matrices provided moderate to strong support for hornworts
as the sister to vascular plants. These results highlight the important roles of
liverworts and hornworts in two major events of plant evolution: the water-to
land transition and the change from a haploid gametophyte generation-dominant
life cycle in bryophytes to a diploid sporophyte generation-dominant life cycle
in vascular plants. This study also demonstrates the importance of using a
multifaceted approach to resolve difficult nodes in the tree of life. In
particular, it is shown here that densely sampled taxon trees built with multiple
genes provide an indispensable test of taxon-sparse trees inferred from genome
sequences.
PMID- 17030816
TI - Transforming reflectance spectra into Munsell color space by using prime colors.
AB - Independent researchers have proved mathematically that, given a set of color
matching functions, there exists a unique set of three monochromatic spectral
lights that optimizes luminous efficiency and color gamut. These lights are
called prime colors. We present a method for transforming reflectance spectra
into Munsell color space by using hypothetical absorbance curves based on
Gaussian approximations of the prime colors and a simplified version of opponent
process theory. The derived color appearance system is represented as a 3D color
system that is qualitatively similar to a conceptual representation of the
Munsell color system. We illustrate the application of the model and compare it
with existing models by using reflectance spectra obtained from 1,269 Munsell
color samples.
PMID- 17030817
TI - Salmon-farming impacts on wild salmon.
PMID- 17030818
TI - Pinoresinol: A lignol of plant origin serving for defense in a caterpillar.
AB - Pinoresinol, a lignan of wide distribution in plants, is found to occur as a
minor component in the defensive secretion produced by glandular hairs of
caterpillars of the cabbage butterfly, Pieris rapae. The compound or a derivative
is appropriated by the larva from its normal food plant (the cabbage, Brassica
oleracea). Pinoresinol was shown to be absent from the secretion if the larva was
given a cabbage-free diet but present in the effluent if that diet was
supplemented with pinoresinol. Pinoresinol is shown to be a feeding deterrent to
ants (Formica exsectoides), indicating that it can complement the defensive
action of the primary components of the secretion, a set of previously reported
lipids called mayolenes. In the test with F. exsectoides, pinoresinol proved to
be more potent than concomitantly tested mayolene-16.
PMID- 17030819
TI - Uncertainty in predictions of disease spread and public health responses to
bioterrorism and emerging diseases.
AB - Concerns over bioterrorism and emerging diseases have led to the widespread use
of epidemic models for evaluating public health strategies. Partly because
epidemic models often capture the dynamics of prior epidemics remarkably well,
little attention has been paid to how uncertainty in parameter estimates might
affect model predictions. To understand such effects, we used Bayesian statistics
to rigorously estimate the uncertainty in the parameters of an epidemic model,
focusing on smallpox bioterrorism. We then used a vaccination model to translate
the uncertainty in the model parameters into uncertainty in which of two
vaccination strategies would provide a better response to bioterrorism, mass
vaccination, or vaccination of social contacts, so-called "trace vaccination."
Our results show that the uncertainty in the model parameters is remarkably high
and that this uncertainty has important implications for vaccination strategies.
For example, under one plausible scenario, the most likely outcome is that mass
vaccination would save approximately 100,000 more lives than trace vaccination.
Because of the high uncertainty in the parameters, however, there is also a
substantial probability that mass vaccination would save 200,000 or more lives
than trace vaccination. In addition to providing the best response to the most
likely outcome, mass vaccination thus has the advantage of preventing outcomes
that are only slightly less likely but that are substantially more horrific.
Rigorous estimates of uncertainty thus can reveal hidden advantages of public
health strategies, suggesting that formal uncertainty estimation should play a
key role in planning for epidemics.
PMID- 17030820
TI - Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic
effects.
AB - A pluripotent cell line, C3H10T1/2, is induced to undergo adipogenesis by a
mixture of factors that includes a glucocorticoid such as dexamethasone. We found
that expression of myostatin (MSTN), a TGF-beta family member extensively studied
in muscle, was induced by dexamethasone under those differentiation conditions.
Moreover, MSTN could substitute for dexamethasone in the adipogenesis mixture.
However, the adipocytes induced by MSTN in both cell culture and transgenic mice
were small and expressed markers characteristic of immature adipocytes. These
adipocytes exhibited cell-autonomous increases in insulin sensitivity and glucose
oxidation. In mice, these effects produced elevated systemic insulin sensitivity
and resistance to diet-induced obesity. Modulation of the final stages of
adipogenesis may provide a novel approach to understanding and treating metabolic
disease.
PMID- 17030821
TI - A beta2-frequency (20-30 Hz) oscillation in nonsynaptic networks of somatosensory
cortex.
AB - Beta2 frequency (20-30 Hz) oscillations appear over somatosensory and motor
cortices in vivo during motor preparation and can be coherent with muscle
electrical activity. We describe a beta2 frequency oscillation occurring in vitro
in networks of layer V pyramidal cells, the cells of origin of the corticospinal
tract. This beta2 oscillation depends on gap junctional coupling, but it survives
a cut through layer 4 and, hence, does not depend on apical dendritic
electrogenesis. It also survives a blockade of alpha-amino-3-hydroxy-5-methyl-4
isoxazolepropionic acid receptors or a blockade of GABA(A) receptors that is
sufficient to suppress gamma (30-70 Hz) oscillations in superficial cortical
layers. The oscillation period is determined by the M type of K+ current.
PMID- 17030822
TI - Eph tyrosine kinase receptor EphA4 is required for the topographic mapping of the
corticospinal tract.
AB - Fine movement in the body is controlled by the motor cortex, which signals in a
topographically specific manner to neurons in the spinal cord by means of the
corticospinal tract (CST). How the correct topography of the CST is established
is unknown. To investigate the possibility that the Eph tyrosine kinase receptor
EphA4 is involved in this process, we have traced CST axons in mice in which the
EphA4 gene has been deleted. The forelimb subpopulation of CST axons is
unaffected in the EphA4-/- mice, but the hindlimb subpopulation branches too
early within the cord, both temporally and spatially. EphA4 shows a dynamic
expression pattern in the environment of the developing CST in the spinal cord:
high at the time of forelimb branching and down-regulated before hindlimb
branching. To examine whether the fore- and hindlimb subpopulations of CST axons
respond differently to EphA4 in their environment, neurons from fore- and
hindlimb motor cortex were cultured on a substrate containing EphA4. Neurons from
the hindlimb cortex showed reduced branching on the EphA4 substrate compared with
their forelimb counterparts. Neurons from the hindlimb cortex express ephrinA5, a
high-affinity ligand for EphA4, at higher levels compared with forelimb cortex
neurons, and this expression is down-regulated before hindlimb branching.
Together, these findings suggest that EphA4 regulates topographic mapping of the
CST by controlling the branching of CST axons in the spinal cord.
PMID- 17030823
TI - An arsenic metallochaperone for an arsenic detoxification pump.
AB - Environmental arsenic is a world-wide health issue, making it imperative for us
to understand mechanisms of metalloid uptake and detoxification. The predominant
intracellular form is the highly mephitic arsenite, which is detoxified by
removal from cytosol. What prevents arsenite toxicity as it diffuses through
cytosol to efflux systems? Although intracellular copper is regulated by
metallochaperones, no chaperones involved in conferring resistance to other
metals have been identified. In this article, we report identification of an
arsenic chaperone, ArsD, encoded by the arsRDABC operon of Escherichia coli. ArsD
transfers trivalent metalloids to ArsA, the catalytic subunit of an
As(III)/Sb(III) efflux pump. Interaction with ArsD increases the affinity of ArsA
for arsenite, thus increasing its ATPase activity at lower concentrations of
arsenite and enhancing the rate of arsenite extrusion. Cells are consequently
resistant to environmental concentrations of arsenic. This report of an arsenic
chaperone suggests that cells regulate the intracellular concentration of
arsenite to prevent toxicity.
PMID- 17030824
TI - Divergent mtDNA lineages of goats in an Early Neolithic site, far from the
initial domestication areas.
AB - Goats were among the first farm animals domesticated, approximately 10,500 years
ago, contributing to the rise of the "Neolithic revolution." Previous genetic
studies have revealed that contemporary domestic goats (Capra hircus) show far
weaker intercontinental population structuring than other livestock species,
suggesting that goats have been transported more extensively. However, the timing
of these extensive movements in goats remains unknown. To address this question,
we analyzed mtDNA sequences from 19 ancient goat bones (7,300-6,900 years old)
from one of the earliest Neolithic sites in southwestern Europe. Phylogenetic
analysis revealed that two highly divergent goat lineages coexisted in each of
the two Early Neolithic layers of this site. This finding indicates that high
mtDNA diversity was already present >7,000 years ago in European goats, far from
their areas of initial domestication in the Near East. These results argue for
substantial gene flow among goat populations dating back to the early
neolithisation of Europe and for a dual domestication scenario in the Near East,
with two independent but essentially contemporary origins (of both A and C
domestic lineages) and several more remote and/or later origins.
PMID- 17030825
TI - The FDA and drug safety: a proposal for sweeping changes.
AB - The current Food and Drug Administration (FDA) system of regulating drug safety
has serious limitations and is in need of changes. The major problems include the
following: the design of initial preapproval studies lets uncommon, serious
adverse events go undetected; massive underreporting of adverse events to the FDA
postmarketing surveillance system reduces the ability to quantify risk
accurately; manufacturers do not fulfill the majority of their postmarketing
safety study commitments; the FDA lacks authority to pursue sponsors who violate
regulations and ignore postmarketing safety study commitments; the public
increasingly perceives the FDA as having become too close to the regulated
pharmaceutical industry; the FDA's safety oversight structure is suboptimal; and
the FDA's expertise and resources in drug safety and public health are limited.
To address these problems, we urge Congress, which is ultimately responsible for
the FDA's performance, to implement the following 5 recommendations: (1) give the
FDA more direct legal authority to pursue violations, (2) authorize the adoption
of a conditional drug approval policy, at least for selected drugs, (3) provide
additional financial resources to support the safety operations, (4) mandate a
reorganization of the agency with emphasis on strengthening the evaluation and
proactive monitoring of drug safety, and (5) require broader representation of
safety experts on the FDA's advisory committees.
PMID- 17030826
TI - Risk of acquiring antibiotic-resistant bacteria from prior room occupants.
AB - BACKGROUND: Environmental contamination with methicillin-resistant Staphylococcus
aureus (MRSA) and vancomycin-resistant enterococci (VRE) occurs during the care
of patients harboring these organisms and may increase the risk of transmission
to subsequent room occupants. METHODS: Twenty-month retrospective cohort study of
patients admitted to 8 intensive care units performing routine admission and
weekly screening for MRSA and VRE. We assessed the relative odds of acquisition
among patients admitted to rooms in which the most recent occupants were MRSA
positive or VRE positive, compared with patients admitted to other rooms.
RESULTS: Of 11 528 intensive care unit room stays, 10 151 occupants were eligible
to acquire MRSA, and 10 349 were eligible to acquire VRE. Among patients whose
prior room occupant was MRSA positive, 3.9% acquired MRSA, compared with 2.9% of
patients whose prior room occupant was MRSA negative (adjusted odds ratio, 1.4; P
= .04). VRE, Among patients whose prior room occupant was VRE positive, these
values were 4.5% and 2.8% respectively (adjusted odds ratio, 1.4; P = .02). These
excess risks accounted for 5.1% of all incident MRSA cases and 6.8% of all
incident VRE cases, with a population attributable risk among exposed patients of
less than 2% for either organism. Acquisition was significantly associated with
longer post-intensive care unit length of stay. CONCLUSIONS: Admission to a room
previously occupied by an MRSA-positive patient or a VRE-positive patient
significantly increased the odds of acquisition for MRSA and VRE. However, this
route of transmission was a minor contributor to overall transmission. The effect
of current cleaning practices in reducing the risk to the observed levels and the
potential for further reduction are unknown.
PMID- 17030827
TI - High prevalence of stroke symptoms among persons without a diagnosis of stroke or
transient ischemic attack in a general population: the REasons for Geographic And
Racial Differences in Stroke (REGARDS) study.
AB - BACKGROUND: A substantial portion of the general population has clinically silent
stroke on brain imaging. These lesions may cause symptoms. This study assessed
the prevalence of stroke symptoms in a stroke- and transient ischemic attack
(TIA)-free population and the association of symptoms with risk factors indexed
by the Framingham Stroke Risk Score. METHODS: We performed a cross-sectional
analysis from a randomly sampled national cohort enrolled from January 25, 2003,
through November 30, 2005, with oversampling from the southeastern stroke belt
and African American populations. The main outcome measure was stroke symptoms
assessed by validated questionnaire. RESULTS: The study included 18 462 (41%
African American; 51% female; mean age, 65.8 years) participants who reported no
stroke or TIA. The prevalence of stroke symptoms was 5.8% for sudden painless
hemibody weakness, 8.5% for sudden hemibody numbness, 4.6% for sudden painless
loss of vision in one or both eyes, 3.1% for sudden hemifield visual loss, 2.7%
for sudden inability to understand speech, and 3.8% for sudden inability of
linguistic expression. The prevalence of 1 or more symptoms was 17.8%. Relative
to the first quartile of the Framingham Stroke Risk Score, the adjusted odds
ratio for 1 or more stroke symptoms increased from 1.0 (95% confidence interval
[CI], 0.90-1.2) in the second quartile to 1.2 (95% CI, 1.1-1.5) and 1.5 (95% CI,
1.3-1.6) in successive quartiles. Symptoms were more prevalent among African
American compared with white participants and among those with lower income,
lower educational level, and fair to poor perceived health status. CONCLUSIONS:
The general population without prior diagnosed stroke or TIA has a high
prevalence of stroke symptoms. The relationship between symptoms and risk factors
suggests that some symptomatic individuals may have had clinically undetected
cerebrovascular events and may benefit from aggressive stroke prophylaxis.
PMID- 17030828
TI - Lifetime cumulative exposure to secondhand smoke and risk of myocardial
infarction in never smokers: results from the Western New York health study, 1995
2001.
AB - BACKGROUND: Although many epidemiologic studies have investigated the association
between exposure to secondhand smoke (SHS) and risk of coronary heart disease
(CHD), few of these studies have assessed exposure measures from different
sources over a lifetime. Therefore, we sought to test the association between
lifetime cumulative exposure to SHS and risk of myocardial infarction (MI) (as an
indication of CHD) among never smokers. METHODS: A population-based case-control
study in which participants were 1541 never smokers (284 cases and 1257 controls)
drawn from 1197 women and men with incident MI and 2850 healthy controls (aged 35
70 years) identified from 2 Western New York counties between 1995 and 2001.
Study subjects were asked to report their exposure to SHS at home, at work, and
in public settings from childhood to their present age. Exposure histories from
each source were combined to form a cumulative lifetime exposure measure.
Multiple logistic regression analysis estimated the association between SHS
exposure and case status adjusted for age, sex, education, body mass index, race,
drinking status, lifetime physical activity, hypertension, diabetes mellitus, and
hypercholesterolemia. RESULTS: After adjustment for covariates, exposure to SHS
was not significantly associated with an increased risk of MI. Compared with
participants in the bottom tertile of SHS exposure, those in the top tertile had
an odds ratio of 1.19 [95% confidence interval, 0.78-1.82] for MI. Virtually all
subjects reported some exposure to SHS over their lifetime, but self-reported
exposures declined over time, especially in the period closest to the interview.
CONCLUSIONS: Exposure to SHS has declined sharply among nonsmokers in recent
years. In the absence of high levels of recent exposure to SHS, cumulative
lifetime exposure to SHS may not be as important a risk factor for MI as
previously thought.
PMID- 17030829
TI - Factors associated with dietary supplement use among prescription medication
users.
AB - BACKGROUND: We examined the patterns of nonvitamin dietary supplement (NVDS) use
among adult prescription medication users in the United States. METHODS: Using
the 2002 National Health Interview Survey, we analyzed factors associated with
NVDS use and prescription medication use in the prior 12 months with descriptive,
chi(2), and logistic regression analysis. RESULTS: In the United States, 21% of
adult prescription medication users reported using NVDSs in the prior 12 months.
Of the respondents who used both prescription medications and NVDSs in the prior
12 months, 69% did not discuss this use with a conventional medical practitioner.
Among adults who used prescription medications in the prior 12 months, the most
commonly used supplements included echinacea, ginseng, ginkgo, garlic, and
glucosamine chondroitin. Prescription medication users with menopause and chronic
gastrointestinal disorders had the highest rates of NVDS use (33% and 28%,
respectively), and prescription medication users with coronary heart disease and
history of myocardial infarction had the lowest rates of use (12% each). In the
adjusted analysis, factors associated with increased use of NVDSs by prescription
medication users included being female, being Hispanic, having more years of
education, living in the West, lacking medical insurance, and having chronic
conditions. Elderly respondents were less likely to use NVDSs. CONCLUSION: One in
4 prescription medication users took an NVDS in the prior 12 months, yet the
majority did not share this with a conventional medical professional.
PMID- 17030830
TI - Risk factors of vitamin B(12) deficiency in patients receiving metformin.
AB - BACKGROUND: Identification of risk factors for metformin-related vitamin B(12)
deficiency has major potential implications regarding the management of diabetes
mellitus. METHODS: We conducted a nested case-control study from a database in
which the source population consisted of subjects who had levels of both serum
vitamin B(12) and hemoglobin A(1c) checked in a central laboratory. We identified
155 cases of diabetes mellitus and vitamin B(12) deficiency secondary to
metformin treatment. Another 310 controls were selected from the cohort who did
not have vitamin B(12) deficiency while taking metformin. RESULTS: A total of 155
patients with metformin-related vitamin B(12) deficiency (mean +/- SD serum
vitamin B(12) concentration, 148.6 +/- 40.4 pg/mL [110 +/- 30 pmol/L]) were
compared with 310 matched controls (466.1 +/- 330.4 pg/mL [344 +/- 244 pmol/L]).
After adjusting for confounders, we found clinically important and statistically
significant association of vitamin B(12) deficiency with dose and duration of
metformin use. Each 1-g/d metformin dose increment conferred an odds ratio of
2.88 (95% confidence interval, 2.15-3.87) for developing vitamin B(12) deficiency
(P<.001). Among those using metformin for 3 years or more, the adjusted odds
ratio was 2.39 (95% confidence interval, 1.46-3.91) (P = .001) compared with
those receiving metformin for less than 3 years. After exclusion of 113 subjects
with borderline vitamin B(12) concentration, dose of metformin remained the
strongest independent predictor of vitamin B(12) deficiency. CONCLUSIONS: Our
results indicate an increased risk of vitamin B(12) deficiency associated with
current dose and duration of metformin use despite adjustment for many potential
confounders. The risk factors identified have implications for planning screening
or prevention strategies in metformin-treated patients.
PMID- 17030831
TI - Annual influenza vaccination in community-dwelling elderly individuals and the
risk of lower respiratory tract infections or pneumonia.
AB - BACKGROUND: Influenza vaccination has been associated with a reduction in the
number of hospitalizations for respiratory conditions in elderly persons over the
period from 1996 to 2002. Little is known, however, about the effect of influenza
vaccination on the whole range of severity of respiratory tract infections.
METHODS: We investigated the effect of annual influenza vaccination on the
occurrence of lower respiratory tract infections (LRTIs) in community-dwelling
elderly individuals. From 1996 to 2002, we performed a population-based cohort
study, using the computerized Integrated Primary Care Information database in the
Netherlands, of community-dwelling subjects who were 65 years or older on January
1 of the year of study entry. For each year, the individual cumulative exposure
to influenza vaccination since study entry was computed. We compared the risk of
LRTI after a first vaccination or revaccination with the risk for no vaccination
using a time-varying multivariate Cox proportional hazard model, adjusted for
age, sex, smoking, and underlying disease. RESULTS: In the study population of 26
071 subjects, 3412 developed LRTIs during follow-up. During the influenza
epidemic periods, a first vaccination did not reduce risk for LRTI. In the total
population, the hazard ratio following a first vaccination was 0.86 (95%
confidence interval [CI], 0.71 to 1.05); in the population without or with
comorbidity, these ratios were 0.90 (95% CI, 0.56 to 1.45) and 0.83 (95% CI, 0.66
to 1.04), respectively. During epidemic periods, revaccination reduced risk of
LRTI by 33% (95% CI, 8% to 52%) in individuals without comorbidity. In
individuals with comorbidity, the risk reduction of 5% was nonsignificant (95%
CI, -10% to 18%). CONCLUSION: In this study, annual influenza revaccination was
associated with a reduction in LRTI in community-dwelling elderly individuals.
PMID- 17030832
TI - Lower extremity nerve function in patients with lower extremity ischemia.
AB - BACKGROUND: We determined whether lower extremity ischemia, as measured by the
ankle brachial index (ABI), is associated with impaired lower extremity nerve
function. METHODS: Participants included 478 persons with peripheral arterial
disease (PAD) identified from noninvasive vascular laboratories and 292 persons
without PAD identified from a general medicine practice and noninvasive vascular
laboratories. Peripheral arterial disease was defined as an ABI lower than 0.90
(mild PAD: ABI, 0.70 to <0.90; moderate PAD: ABI, 0.50 to <0.70; and severe PAD:
ABI, <0.50). The ABI and electrophysiologic measures of the peroneal, sural, and
ulnar nerves were obtained. RESULTS: Among 546 participants without diabetes, PAD
participants had significantly impaired peripheral nerve function in the upper
and lower extremities compared with non-PAD participants. After adjusting for
age, sex, race, smoking, height, body mass index, recruitment source, alcohol
use, disk disease, spinal stenosis, cardiac disease, and cerebrovascular disease,
these associations were not statistically significant. After adjusting for
confounders among nondiabetic participants, those with severe PAD (ABI, <0.50)
had poorer peroneal nerve conduction velocity (NCV) compared with participants
without PAD (42.6 vs 44.8 m/s; P = .003) and poorer peroneal NCV compared with
participants with mild PAD (42.6 vs 45.0 m/s; P = .001) or moderate PAD (42.6 vs
44.1 m/s; P = .03). Among 224 participants with diabetes, after adjusting for
confounders, PAD was associated with poorer peroneal NCV (40.8 vs 43.5 m/s; P =
.01), sural nerve amplitude (3.1 vs 4.8 muV; P = .045), and ulnar NCV (47.6 vs
50.2 m/s; P = .03) compared with those without PAD. CONCLUSIONS: Our findings
suggest that leg ischemia impairs peroneal nerve function. This association is
less strong in patients with diabetes, perhaps because of the overriding
influence of diabetes on peripheral nerve function. Clinicians should consider
screening for PAD in patients with idiopathic peroneal nerve dysfunction.
Peripheral arterial disease-associated nerve dysfunction may contribute to PAD
associated functional impairment.
PMID- 17030833
TI - Brain dysfunction: another burden for the chronically critically ill.
AB - BACKGROUND: Chronic critical illness is a devastating syndrome of prolonged
respiratory failure and other derangements. To our knowledge, no previous
research has addressed brain dysfunction in the chronically critically ill,
although this topic is important for medical decision making. METHODS: We studied
a prospective cohort of 203 consecutive, chronically critically ill adults
transferred to our hospital's respiratory care unit (RCU) after tracheotomy for
failure to wean. We measured prevalence and duration of coma and delirium during
RCU treatment using the Confusion Assessment Method for the Intensive Care Unit
with the Richmond Agitation-Sedation Scale. To assess survivors (at 3 and 6
months after RCU discharge), we used a validated telephone Confusion Assessment
Method. RESULTS: Before hospitalization, most (153 [75.4%]) of the 203 patients
in the study were at home, completely independent (115 [56.7%]), and cognitively
intact (116 [82.0%]). In the RCU, 61 (30.0%) were comatose throughout the stay.
Approximately half of patients (66 of 142) who were not in coma were delirious.
Patients spent an average of 17.9 days (range, 1-153 days) in coma or delirium
(average RCU stay, 25.6 days). Half of survivors (79 of 160) had one of these
disturbances at RCU discharge. At 6 months, three fourths (151) of the study
patients were dead or institutionalized; of 85 survivors, 58 (68.2%) were too
profoundly impaired to respond to telephone cognitive assessment, and 53 (62.4%)
were dependent in all activities of daily living. CONCLUSIONS: Severe, prolonged,
and permanent brain dysfunction is a prominent feature of chronic critical
illness. These data, together with previous reports of symptom distress and rates
of mortality and institutionalization, describe burdens for chronically
critically ill patients receiving continued life-prolonging treatment and for
their families.
PMID- 17030834
TI - Quality-of-life impact and treatment of urinary incontinence in ethnically
diverse older women.
AB - OBJECTIVE: To identify the factors associated with greater quality-of-life
impact, treatment seeking, and use of treatments for urinary incontinence in
ethnically diverse older women. METHODS: Cross-sectional analysis of a population
based cohort of 2109 middle-aged and older women who were randomly selected from
age and race/ethnicity strata. Data were collected by self-report questionnaires
and in-person interviews. Multivariable logistic regression was used to identify
predictors of high quality-of-life impact (Incontinence Impact Questionnaire
[IIQ] score > or =75th percentile), treatment seeking, and use of treatments for
incontinence. RESULTS: More than one fourth (n = 603) of the study participants
(including 96 black [16%], 123 Latina [20%], 65 Asian [11%], and 309 white [51%]
women) reported weekly incontinence. After clinical severity and other factors
were adjusted for, women were more likely to experience high quality-of-life
impact if they had nighttime incontinence (odds ratio [OR], 2.5; 95% confidence
interval [CI], 1.3-4.9), coital incontinence (OR, 1.9; 95% CI, 1.1-3.3), or
comorbid fecal incontinence (OR, 2.2; 95% CI, 1.2-4.2). Predictors of treatment
seeking included older age (OR, 1.6 per 10 years; 95% CI, 1.2-2.0); higher IIQ
score (OR, 4.6 for highest IIQ quartile vs lowest IIQ quartile; 95% CI, 2.5-8.4),
and higher household income (OR, 2.6 for income > or = US dollars 100 000/y vs <
US dollars 20 000/y; 95% CI, 1.0-2.7). CONCLUSIONS: Clinicians seeking to
evaluate the impact of incontinence on women's lives should assess not only the
clinical severity of their symptoms but also the specific context in which
symptoms occur. The prevalence of treatment seeking for incontinence is low
across all ethnic groups, even when women have clinically severe symptoms and
access to a health provider.
PMID- 17030835
TI - Mannose-binding lectin and mortality in type 2 diabetes.
AB - BACKGROUND: Inflammation and complement activation initiated by mannose-binding
lectin (MBL) may be implicated in the pathogenesis of diabetic vascular
complications. We evaluated the relationship between serum MBL and mortality and
development of albuminuria in type 2 diabetes. METHODS: Levels of MBL and C
reactive protein (CRP) were measured at baseline in 326 patients with type 2
diabetes who attended the Steno Diabetes Center, Gentofte, Denmark, for control.
Urinary albumin excretion was determined annually, and the vital status of all
patients was traced after more than 15 years of follow-up. RESULTS: During follow
up, 169 patients died. The risk of dying was significantly higher among patients
with MBL levels greater than or equal to 1000 microg/L than among patients with
levels less than 1000 microg/L (hazard ratio, 1.5; 95% confidence interval, 1.1
2.1; P = .005). After adjustment for known confounders, MBL remained a
significant risk factor for death from any cause. It added to the predictive
power of CRP, and mortality was significantly higher among patients with both
high MBL (> or =1000 microg/L) and high CRP (above the median, 3.6 mg/L) levels
than among patients with both low MBL and low CRP levels (hazard ratio, 2.7; 95%
confidence interval, 1.7-4.3; P<.001). Normoalbuminuric patients with both high
MBL and high CRP levels at baseline had a significantly increased risk of
developing microalbuminuria or macroalbuminuria compared with patients with both
low MBL and low CRP levels (hazard ratio, 2.6; 95% confidence interval, 1.5-4.4;
P<.001). CONCLUSION: In patients with type 2 diabetes, measurements of MBL alone
or in combination with CRP can provide prognostic information on mortality and
the development of albuminuria.
PMID- 17030836
TI - Impact of chronic kidney disease on health-related quality-of-life improvement
after coronary artery bypass surgery.
AB - BACKGROUND: Little is known about the impact of chronic kidney disease (CKD) on
health-related quality-of-life outcomes after coronary artery bypass grafting
(CABG). METHODS: Our objective was to examine the changes in physical function
(PF) and mental health (MH) 6 months after CABG in 1055 patients with and without
CKD. The primary end points were mean change in score and status of "improved" or
"worsened" in both PF and MH subscales of the Medical Outcomes Trust Short Form
36-Item Health Survey from baseline to 6 months after CABG, stratified by CKD
stage (0-5). RESULTS: Absolute PF and MH scores at baseline and at 6 months
varied by renal impairment level. Patients with severe CKD (stages 4-5) had a
mean (SD) decrease in PF score at 6 months of 3 (3) compared with increases in
the rest of the cohort (P<.001). After adjustment for baseline score, 21% of
patients with advanced CKD experienced worsened PF scores, compared with 0% of
patients with stages 0 to 2 and stage 3 CKD (P<.001). In contrast to PF scores,
patients with and without CKD had similar improvements in mean MH scores at 6
months, and patients with stages 4 to 5 CKD had the highest frequency of those
with improved MH scores (77%). After adjustment, no patients experienced worsened
MH scores. CONCLUSIONS: After 6 months, patients with severe CKD who underwent
CABG had improvement in MH but not improvement in PF and may have had worsened PF
compared with those without severe CKD. Comparable evidence regarding quality-of
life outcomes in the absence of CABG is needed to more fully inform decision
making regarding patients with severe CKD and coronary artery disease.
PMID- 17030837
TI - An evaluation of screening questions for childhood abuse in 2 community samples:
implications for clinical practice.
AB - BACKGROUND: A number of practice guidelines and recommendations call for the
assessment of childhood abuse in adult medical patients, but none specifies how
best to do this. The objective of this study was to use evidence from 2 community
based population samples to evaluate abuse-screening questions that are often
asked in medical clinics and to identify a small set of questions to improve
screening practices. METHODS: The Childhood Trauma Questionnaire-Short Form (CTQ
SF) was administered in 2 randomized telephone interview surveys with adults aged
18 to 65 years. RESULTS: A total of 880 (2003 survey) and 998 (1997 survey)
respondents completed the CTQ-SF in the 2 surveys. In both surveys, the rates of
physical (16% and 15%), emotional (31% and 29%), and sexual (10% and 9%) abuse
elicited using 3 behaviorally descriptive items in each abuse category were
approximately twice the rates elicited using the explicit labeling terms
physically abused (8% and 8%), emotionally abused (15% and 13%), or sexually
abused (5% and 5%) (P<.001 for each). Inquiries explicitly using the labeling
term abuse successfully identified a low percentage of respondents who reported
behaviorally described abusive experiences for each type of abuse (34%-51%). In
addition, after adjustment for the number and frequency of abusive experiences in
both surveys, women were more likely than men to label themselves as explicitly
abused for any abuse (odds ratio [OR], 1.7; P = .11 and OR, 2.8; P<.01), physical
abuse (OR, 2.1; P = .14 and OR, 2.9; P<.01), emotional abuse (OR, 2.7; P<.01 and
OR, 3.3; P<.01), and sexual abuse (OR, 3.5; P = .08 and OR, 1.5; P = .55).
CONCLUSION: Inquiries about childhood abuse that use broad labeling questions
identify a substantially smaller number of patients than behaviorally specific
questions and may be less effective in initial screening for a history of abuse.
PMID- 17030838
TI - Recent trends in the care of patients with non-ST-segment elevation acute
coronary syndromes: insights from the CRUSADE initiative.
AB - BACKGROUND: The extent to which national health quality improvement initiatives
have altered reported treatment gaps among patients with non-ST-segment elevation
acute coronary syndromes (NSTE ACS) is unknown. We sought to determine recent
trends in adherence to guideline-based therapies for NSTE ACS. METHODS: We
evaluated the treatment of patients with high-risk (positive cardiac markers
and/or ischemic ST-segment changes) NSTE ACS enrolled in the Can Rapid Risk
Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early
Implementation of the ACC/AHA (American College of Cardiology/American Heart
Association) Guidelines (CRUSADE) Quality Improvement Initiative from 2002
through 2004 (a total of 113 595 patients over 11 calendar quarters). We analyzed
adherence to guideline-recommended therapies, including medications used in the
acute care period (<24 hours after presentation), invasive procedures, in
hospital outcomes, and discharge therapies and interventions. RESULTS: The use of
each class I guideline recommendation, as well as overall adherence to the
guidelines, improved significantly (P<.001) during the study period. In the acute
care setting, the use of antiplatelet agents increased by 5% and beta-blockers by
12%; at hospital discharge, the use of antiplatelet agents increased by 3% and
beta-blockers by 8%. Heparin use in the acute care period increased by 6%,
largely owing to a 9% increase in the use of low-molecular-weight heparin. Use of
glycoprotein IIb/IIIa inhibitors in the acute care period also increased by more
than 13%. At discharge, clopidogrel use increased by 22%, lipid-lowering agents
by 11%, and angiotensin-converting enzyme inhibitors by 5%. While adherence
improved, many patients still failed to receive 100% indicated treatments at the
end of the study period. CONCLUSIONS: During the 4 years since the initial
release of the ACC/AHA guidelines for NSTE ACS, adherence to class I
recommendations has significantly improved among hospitals participating in
CRUSADE. Still, further improvements are needed for optimal implementation of the
these guidelines.
PMID- 17030839
TI - Time course of depression and outcome of myocardial infarction.
AB - BACKGROUND: Depression predicts worse outcomes after myocardial infarction (MI),
but whether its time course in the month following MI has prognostic importance
is unknown. Our objective was to evaluate the prognostic importance of transient,
new, or persistent depression on outcomes at 6 months after MI. METHODS: In a
prospective registry of acute MI (Prospective Registry Evaluating outcomes after
Myocardial Infarction: Events and Recovery [PREMIER]), depressive symptoms were
measured in 1873 patients with the Patient Health Questionnaire (PHQ) during
hospitalization and 1 month after discharge and were classified as transient
(only at baseline), new (only at 1 month), or persistent (at both times).
Outcomes at 6 months included (1) all-cause rehospitalization or mortality and
(2) health status (angina, physical limitation, and quality of life using the
Seattle Angina Questionnaire). RESULTS: Compared with nondepressed patients, all
categories of depression were associated with higher rehospitalization or
mortality rates, more frequent angina, more physical limitations, and worse
quality of life. The adjusted hazard ratios for rehospitalization or mortality
were 1.34, 1.71, and 1.42 for transient, new, and persistent depression,
respectively (all P<.05). Corresponding odds ratios were 1.62, 2.73, and 2.64
(all P<.01) for angina and 1.69, 2.25, and 3.27 (all P<.05) for physical
limitation. Depressive symptoms showed a stronger association with health status
compared with traditional measures of disease severity. CONCLUSION: Depressive
symptoms after MI, irrespective of whether they persist, subside, or newly
develop in the first month after hospitalization, are associated with worse
outcomes after MI.
PMID- 17030840
TI - Acquired hydrocephalus caused by a variant lymphocytic choriomeningitis virus.
PMID- 17030841
TI - Ignoring study design heterogeneity in meta-analyses.
PMID- 17030842
TI - Morphine is not a sedative and does not shorten life.
PMID- 17030843
TI - Protecting the health of the public--Institute of Medicine recommendations on
drug safety.
PMID- 17030844
TI - Blueprint for a stronger Food and Drug Administration.
PMID- 17030845
TI - Chimeric Japanese encephalitis virus/dengue 2 virus infectious clone: biological
properties, immunogenicity and protection against dengue encephalitis in mice.
AB - A molecular clone of Japanese encephalitis virus (JE virus) was derived from the
JE virus Nakayama strain and used to produce infectious JE virus in cell culture.
The engineered JE virus resembled the parental JE virus in cell-culture
properties and was related closely to other JE virus strains based on nucleotide
sequence analysis. The JE virus clone was used as a genetic background for
construction of a chimeric virus containing the structural proteins prM and E of
Dengue virus, serotype 2. The chimeric JE/dengue 2 virus generated authentic
dengue 2 structural proteins as assessed by immunoassays for the dengue E
protein. It exhibited a small plaque size and less efficient growth in various
cell lines than the parental JE virus. JE/dengue 2 virus was non-neuroinvasive
for young adult mice, but displayed partial neurovirulence at doses up to 4 log
p.f.u. given intracerebrally. Immunization of 3-week-old mice with JE/dengue 2
virus yielded neutralizing-antibody titres against dengue 2 virus and conferred
protection against dengue encephalitis caused by neuroadapted dengue 2 virus. A
rise in post-challenge neutralizing-antibody titres against dengue 2 virus in
surviving mice suggests that immunization is associated with establishment of a
memory antibody response in this model. This study demonstrates the capacity of
JE virus to serve as a vector for expression of heterologous flavivirus
structural proteins. Similar to previous studies with other chimeric
flaviviruses, this approach may be useful as a genetic system for engineering
experimental vaccines against Dengue virus and other medically important
flaviviruses.
PMID- 17030846
TI - PrP genotypes of atypical scrapie cases in Great Britain.
AB - Great Britain and elsewhere have detected atypical scrapie infection in sheep
with PrP genotypes thought to be genetically resistant to the classical form of
scrapie. DNA sequencing of the PrP gene of British atypical scrapie cases (n=69),
classical scrapie cases (n=59) and scrapie-free controls (n=138) was undertaken
to identify whether PrP variants, other than the three well-characterized
polymorphic codons, influenced susceptibility to atypical scrapie infection. Four
non-synonymous changes, M112T, M137T, L141F and P241S, were detected that are
most probably associated with the A(136)R(154)Q(171) haplotype. Only the PrP
variant containing a phenylalanine residue at amino acid position 141 was found
to be associated more commonly with the atypical scrapie cases. In addition to
the single nucleotide polymorphisms associated with the ARQ allele, two out of
nine atypical scrapie cases with the ARR/ARR genotype were found to contain a 24
bp insertion, leading to an additional octapeptide repeat. In terms of PrP
genetics, one classification of the GB scrapie cases examined in this study would
place animals carrying any homozygous or heterozygous combination of ARR, AHQ or
AF(141)RQ alleles, or any one of these alleles when paired with ARQ, as being
susceptible to atypical scrapie infection, and animals heterozygous or homozygous
for VRQ or homozygous for ARQ as being susceptible to classical scrapie disease.
The AHQ PrP allele was associated with the highest incidence of atypical scrapie
(263 per 100 000 alleles), whilst VRQ was associated with the lowest incidence
(10 per 100 000 alleles).
PMID- 17030847
TI - Adenovirus type 5 fiber knob domain has a critical role in fiber protein
synthesis and encapsidation.
AB - Adenovirus serotype 5 (Ad5) vectors carrying knobless fibers designed to remove
their natural tropism were found to have a lower fiber content than recombinant
Ad5 with wild-type (WT) capsid, implying a role for the knob-coding sequence
or/and the knob domain in fiber encapsidation. Experimental data using a variety
of fiber gene constructs showed that the defect did not occur at the fiber mRNA
level, but at the protein level. Knobless fiber proteins were found to be
synthesized at a significant slower rate compared with knob-carrying fibers, and
the trimerization process of knobless fibers paralleled their slow rate of
synthesis. A recombinant Ad5 diploid for the fiber gene (referred to as Ad5/R7
ZZ(wt)/E1 : WT-fiber) was constructed to analyse the possible rescue of the
knobless low-fiber-content phenotype by co-expression of WT fiber. Ad5/R7
ZZ(wt)/E1 : WT-fiber contained a knobless fiber gene in its natural location (L5)
in the viral genome and an additional WT fiber gene in an ectopic position in E1.
Knobless fiber was still synthesized at low levels compared with the co-expressed
E1 : WT fiber and the recovery of the two fiber species in virus progeny
reflected their respective amounts in the infected cells. Our results suggested
that deletion of the fiber knob domain had a negative effect on the translation
of the fiber mRNA and on the intracellular concentration of fiber protein. They
also suggested that the knob control of fiber protein synthesis and encapsidation
occurred as a cis effect, which was not modified by WT fiber protein provided in
trans by the same Ad5 genome.
PMID- 17030848
TI - Adenovirus RID complex enhances degradation of internalized tumour necrosis
factor receptor 1 without affecting its rate of endocytosis.
AB - The receptor internalization and degradation (RID) complex of adenovirus plays an
important role in modulating the immune response by downregulating the surface
levels of tumour necrosis factor receptor 1 (TNFR1), thereby inhibiting NF-kappaB
activation. Total cellular content of TNFR1 is also reduced in the presence of
RID, which can be inhibited by treatment with lysosomotropic agents. In this
report, surface biotinylation experiments revealed that, although RID and TNFR1
were able to form a complex on the cell surface, the rate of TNFR1 endocytosis
was not affected by RID. However, the degradation of internalized TNFR1 was
enhanced significantly in the presence of RID. Therefore, these data suggest that
RID downregulates TNFR1 levels by altering the fate of internalized TNFR1 that
becomes associated with RID at the plasma membrane, probably by promoting its
sorting into endosomal/lysosomal degradation compartments.
PMID- 17030849
TI - The CR4 region of EBNA2 confers viability of Epstein-Barr virus-transformed B
cells by CBF1-independent signalling.
AB - The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) gene product is the key
regulator of the latent genes of EBV and essential for EBV-mediated
transformation of human primary B cells. Viral mutants were constructed carrying
a deletion of the EBNA2 conserved region 4 (CR4). Primary resting B cells
infected with the DeltaCR4-EBNA2 mutant virus were dramatically impaired for B
cell transformation. Lymphoblastoid cell lines (LCLs) established with this
mutant EBV revealed a prolonged population doubling time when cells were
cultivated at low cell densities, which are not critical for wild-type-infected
cells. Low-level spontaneous cell death occurred when the cells were cultivated
at suboptimal cell densities. The phenotype of B cells and LCLs infected with the
DeltaCR4-EBNA2 mutant virus indicated that the CR4 region of EBNA2 specifically
contributes to the viability of the cells rather than affecting cell division
rates.
PMID- 17030850
TI - Maturation and function of human dendritic cells are inhibited by orf virus
encoded interleukin-10.
AB - Orf virus (ORFV) is a parapoxvirus that infects sheep, goats and man. In humans,
the virus induces acute, pustular skin lesions that can develop into a
progressive disease. Humans are susceptible to reinfection with ORFV and rare
cases of persistent infection have been reported. ORFV encodes several
immunomodulators, including a homologue of interleukin-10 (ORFV IL-10), that may
explain these phenomena. The immunosuppressive effects of ORFV IL-10 on immature
human dendritic cells (DCs) cultured from blood-derived monocytes (MoDCs) were
investigated. MoDCs exposed simultaneously to lipopolysaccharide and ORFV IL-10
showed enhanced ovalbumin-FITC uptake and reduced IL-12 expression, indicating
inhibition of maturation. Moreover, ORFV IL-10 inhibited the upregulation of DC
cell-surface activation and maturation markers MHC II, CD80, CD83 and CD86 and
inhibited the capacity of MoDCs to activate CD4(+) T cells in an oxidative
mitogenesis assay. These findings suggest that ORFV IL-10 may influence the
development of acquired immunity in humans by impairing DC function.
PMID- 17030851
TI - Human papillomaviruses target the double-stranded RNA protein kinase pathway.
AB - The double-stranded RNA protein kinase (PKR) pathway plays a vital role in the
innate immune response to viral infection. Activation of PKR following virus
entry can lead to a shutdown in translation, thereby inhibiting viral protein
synthesis and replication. Little is currently known about whether human
papillomaviruses (HPVs) modulate PKR expression and activity. In this study,
normal human foreskin keratinocytes (NHKs) transfected stably with the HPV 31 or
16 genomes and cell lines expressing the HPV 16 E6 and E7 oncoproteins were used
to examine effects on the PKR pathway. HPV gene products were found to modulate
PKR phosphorylation, activity and localization. The levels of total PKR protein
were reduced modestly in cells that maintained HPV 16 or 31 episomes through a
reduction in PKR transcription. However, levels of phosphorylated PKR were
decreased 4-fold through a post-transcriptional mechanism mediated by E6 and E7
that was independent of the transcriptional downregulation mediated by HPV. In
response to infection by vesicular stomatitis virus, phosphorylation of eIF2alpha
was blocked in cells expressing HPV oncoproteins, but not in NHKs. Finally, it
was observed that the cellular localization of PKR was altered by HPV gene
products in HPV raft cultures, as well as HPV-positive patient biopsies. This
effect was mediated by the HPV E6 oncoprotein and leads to the co-localization of
PKR with P-bodies. These studies demonstrate that high-risk HPVs target the PKR
pathway by multiple mechanisms.
PMID- 17030852
TI - Papillomavirus in healthy skin of Australian animals.
AB - Papillomaviruses are a group of ubiquitous viruses that are often found in normal
skin of humans, as well as a range of different vertebrates. In this study, swab
samples collected from the healthy skin of 225 Australian animals from 54 species
were analysed for the presence of papillomavirus DNA with the general skin
papillomavirus primer pair FAP59/FAP64. A total of five putative and potential
new animal papillomavirus types were identified from three different animal
species. The papillomaviruses were detected in one monotreme and two marsupial
species: three from koalas, and one each from an Eastern grey kangaroo and an
echidna. The papillomavirus prevalence in the three species was 14 % (10/72) in
koalas, 20 % (1/5) in echidnas and 4 % (1/23) in Eastern grey kangaroos.
Phylogenetic analysis was performed on the putative koala papillomavirus type
that could be cloned and it appears in the phylogenetic tree as a novel putative
papillomavirus genus. The data extend the range of species infected by
papillomaviruses to the most primitive mammals: the monotremes and the
marsupials.
PMID- 17030853
TI - Identification of a genomic subgroup of BK polyomavirus spread in European
populations.
AB - BK polyomavirus (BKV) is highly prevalent in the human population, infecting
children without obvious symptoms and persisting in the kidney in a latent state.
In immunosuppressed patients, BKV is reactivated and excreted in urine. BKV
isolates worldwide are classified into four serologically distinct subtypes, I
IV, with subtype I being the most frequently detected. Furthermore, subtype I is
subdivided into subgroups based on genomic variations. In this study, the
distribution patterns of the subtypes and subgroups of BKV were compared among
four patient populations with various immunosuppressive states and of various
ethnic backgrounds: (A) Finnish renal-transplant recipients; (B) Irish/English
haematopoietic stem-cell transplant recipients with and without haemorrhagic
cystitis; (C) Japanese renal-transplant recipients; and (D) Japanese bone-marrow
transplant recipients. The typing sequences (287 bp) of BKV in population A were
determined in this study; those in populations B-D have been reported previously.
These sequences were subjected to phylogenetic and single nucleotide polymorphism
analyses. Based on the results of these analyses, the BKV isolates in the four
patient populations were classified into subtypes and subgroups. The incidence of
subtype IV varied significantly among patient populations. Furthermore, the
incidence of subgroup Ib-2 within subtype I was high in populations A and B,
whereas that of Ic was high in populations C and D (P<0.01). These results
suggest that subgroup Ib-2 is widespread among Europeans, whereas Ic is unique to
north-east Asians. Furthermore, a phylogenetic analysis based on complete BKV DNA
sequences supported the hypothesis that there is geographical separation of
European and Asian BKV strains.
PMID- 17030854
TI - Parvoviral nuclear import: bypassing the host nuclear-transport machinery.
AB - The parvovirus Minute virus of mice (MVM) is a small DNA virus that replicates in
the nucleus of its host cells. However, very little is known about the mechanisms
underlying parvovirus' nuclear import. Recently, it was found that microinjection
of MVM into the cytoplasm of Xenopus oocytes causes damage to the nuclear
envelope (NE), suggesting that the nuclear-import mechanism of MVM involves
disruption of the NE and import through the resulting breaks. Here, fluorescence
microscopy and electron microscopy were used to examine the effect of MVM on host
cell nuclear structure during infection of mouse fibroblast cells. It was found
that MVM caused dramatic changes in nuclear shape and morphology, alterations of
nuclear lamin immunostaining and breaks in the NE of infected cells. Thus, it
seems that the unusual nuclear-import mechanism observed in Xenopus oocytes is in
fact used by MVM during infection of host cells.
PMID- 17030855
TI - Porcine circovirus type 2 replicase binds the capsid protein and an intermediate
filament-like protein.
AB - Porcine circovirus type 2 (PCV2) is an important porcine pathogen that
establishes persistent subclinical infections but may, on activation, contribute
to the development of post-weaning multisystemic wasting syndrome (PMWS). This
disease is characterized by weight loss, respiratory or digestive disorders and
enlarged lymph nodes with lymphocyte depletion. The molecular mechanisms behind
the development of the disease are completely unknown. In order to clarify
functions of the different viral proteins and, if possible, to connect these new
findings to molecular mechanisms behind the pathogenesis or the viral life cycle,
a bacterial two-hybrid screening of a porcine expression library from PK-15A
cells was conducted. Using viral proteins corresponding to ORFs 1, 2, 3 and 4 as
bait, a number of interactions were identified and two of them were chosen for
further characterization. GST pull-down assays confirmed that viral replicase
(Rep) interacted with an intermediate filament protein, similar to human
syncoilin, and with the transcriptional regulator c-myc. Furthermore,
interactions of the viral proteins to each other revealed an interaction between
PCV2 Rep and the capsid (Cap) protein and Cap to itself.
PMID- 17030856
TI - Rise in gamma interferon expression during resolution of duck hepatitis B virus
infection.
AB - Gamma interferon (IFN-gamma) expression plays a crucial role in the control of
mammalian hepatitis B virus (HBV) infection. However, the role of duck INF-gamma
(DuIFN-gamma) in the outcome of duck HBV (DHBV) infection, a reference model for
hepadnavirus replication studies, has not yet been investigated. This work
explored the dynamics of DuIFN-gamma expression in liver and peripheral blood
mononuclear cells (PBMCs) during resolution of DHBV infection in adolescent ducks
in relation to serum and liver markers of virus replication, histological changes
and humoral response induction. DHBV infection of 3-week-old ducks resulted in
transient expression of intrahepatic preS protein (days 3-14) and mild
histological changes. Low-level viraemia was detected only during the first 10
days of infection and was accompanied by early anti-preS antibody response
induction. Importantly, a strong increase in intrahepatic DuIFN-gamma RNA was
detected by real-time RT-PCR at days 6-14, which coincided with a sharp decrease
in both viral DNA and preS protein in the liver. Interestingly, liver DuIFN-gamma
expression remained augmented to the end of the follow-up period (day 66) and
correlated with portal lymphocyte infiltration and persistence of trace
quantities of intrahepatic DHBV DNA in animals that had apparently completely
resolved the infection. Moreover, in infected ducks, a moderate increase was
detected in the levels of DuIFN-gamma in PBMCs (days 12-14), which coincided with
the peak in liver DuIFN-gamma RNA levels. These data reveal that increased DuIFN
gamma expression in liver and PBMCs is concomitant with viral clearance,
characterizing the resolution of infection, and provide new insights into the
host-virus interactions that control DHBV infection.
PMID- 17030857
TI - Genome of the most widely used viral biopesticide: Anticarsia gemmatalis multiple
nucleopolyhedrovirus.
AB - The genome of Anticarsia gemmatalis multiple nucleopolyhedrovirus isolate 2D
(AgMNPV-2D), which is the most extensively used virus pesticide in the world, was
completely sequenced and shown to have 132 239 bp (G+C content 44.5 mol%) and to
be capable of encoding 152 non-overlapping open reading frames (ORFs). Three ORFs
were unique to AgMNPV-2D, one of which (ag31) had similarity to eukaryotic
poly(ADP-ribose) polymerases. The lack of chiA and v-cath may explain some of the
success and growth of the AgMNPV biological control programme, as it may explain
the high recovery of polyhedra sequestered inside dead larvae in the field, which
are collected and used for further application as biological pesticides in
soybean fields. The genome organization was similar to that of the Choristoneura
fumiferana defective MNPV (CfDefNPV). Most of the variation between the two
genomes took place near highly repetitive regions, which were also closely
associated with bro-coding regions. The separation of the NPVs into groups I and
II was supported by: (i) a phenogram of the complete genomes of 28 baculovirus
and Heliothis zea virus 1, (ii) the most parsimonious reconstruction of gene
content along the phenograms and (iii) comparisons of genomic features. Moreover,
these data also reinforced the notion that group I of the NPVs can be split
further into the AgMNPV lineage (AgMNPV, CfDefNPV, Epiphyas postvittana NPV,
Orgyia pseudotsugata MNPV and C. fumiferana MNPV), sharing eight defining genes,
and the Autographa californica MNPV (AcMNPV) lineage (AcMNPV, Rachiplusia ou NPV
and Bombyx mori NPV), sharing nine defining genes.
PMID- 17030858
TI - Cap-dependent and hepatitis C virus internal ribosome entry site-mediated
translation are modulated by phosphorylation of eIF2alpha under oxidative stress.
AB - Chronic hepatitis C is often associated with oxidative stress. Hepatitis C virus
(HCV) utilizes an internal ribosome entry site (IRES) element for translation, in
contrast to cap-dependent translation of the majority of cellular proteins. To
understand how virus translation is modulated under oxidative stress, HCV IRES
mediated translation was compared with cap-dependent translation using a
bicistronic reporter construct and hydrogen peroxide (H2O2) as a stress inducer.
In H2O2-sensitive HeLa cells, H2O2 repressed translation in a time- and dose
dependent manner, concomitant with the kinetics of eIF2alpha phosphorylation. A
phosphomimetic of eIF2alpha, which mimics the structure of the phosphorylated
eIF2alpha, was sufficient to repress translation in the absence of H2O2. In H2O2
resistant HepG2 cells, H2O2 activated both HCV IRES-mediated and cap-dependent
translation, associated with an increased level of phospho-eIF2alpha. It was
postulated that H2O2 might stimulate translation in HepG2 cells via an eIF2alpha
independent mechanism, whereas the simultaneous phosphorylation of eIF2alpha
repressed part of the translational activities. Indeed, the translational
repression was released in the presence of a non-phosphorylatable mutant,
eIF2alpha-SA, resulting in further enhancement of both translational activities
after exposure to H2O2. In HuH7 cells, which exhibited an intermediate level of
sensitivity towards H2O2, both HCV IRES-mediated and cap-dependent translational
activities were upregulated after treatment with various doses of H2O2, but the
highest level of induction was achieved with a low level of H2O2, which may
represent the physiological level of H2O2. At this level, the HCV IRES-mediated
translation was preferentially upregulated compared with cap-dependent
translation.
PMID- 17030859
TI - Dual topology of the processed hepatitis C virus protein NS4B is influenced by
the NS5A protein.
AB - Among the least-known hepatitis C virus proteins is the non-structural protein 4B
(NS4B). It localizes to the endoplasmic reticulum (ER) membrane and induces
membrane changes, resulting in a membranous web that is reported to be the locale
for virus replication. A model was presented previously for the topology of
recombinant HCV NS4B of the 1a genotype based on in vitro data. In this model,
the N-terminal tail of a considerable fraction of the NS4B molecules was
translocated into the ER lumen via a post-translational process, giving the
protein a dual transmembrane topology. It is now reported that translocation of
the N terminus also occurs for processed NS4B expressed in cells in the context
of the polyprotein. In the presence of NS5A, however, a lower degree of
translocation was observed, which may indicate that NS5A influences the topology
of NS4B. In vitro expression studies of NS4B from all major genotypes
demonstrated that translocation of the N terminus to the ER lumen is conserved
across genotypes. This clearly suggests an important function for this feature.
Furthermore, when disrupting a previously reported amphipathic helix (AH) in the
N terminus of NS4B, translocation was inhibited. As a disrupted AH also abolished
the ability of NS4B to rearrange membranes, these data indicate for the first
time an association between translocation of the N terminus and membrane
rearrangement. Finally, the present experiments also confirm the predicted
location of the first luminal loop to be around aa 112.
PMID- 17030860
TI - Ngoye virus: a novel evolutionary lineage within the genus Flavivirus.
AB - By using degenerate primers deduced from conserved patterns in the flavivirus
polymerase gene, a novel RNA virus was discovered in Rhipicephalus ticks sampled
from members of the family Bovidae in Senegal. It was named Ngoye virus (NGOV)
after the location from which it was isolated. Viral particles could be observed
by electron microscopy, but isolation in vertebrate or invertebrate cell lines or
by intracerebral infection of newborn mice remained unsuccessful. This is
atypical of recognized arboviruses. The characterization of 4176 nt of the non
structural genes revealed that NGOV is a novel flavivirus species. It forms a
distinct phylogenetic lineage related distantly to previously identified members
of the genus Flavivirus. Analysis of genetic data suggested that the processing
of the NGOV polyprotein and the organization of its replication complex are
similar to those of flaviviruses. Together with other recent data, these findings
suggest that a large number of viruses related distantly to 'classical' arthropod
borne flaviviruses remain to be discovered.
PMID- 17030861
TI - Mutagenesis analysis of the NS2B determinants of the Alkhurma virus NS2B-NS3
protease activation.
AB - Alkhurma virus (ALKV) is a tick-borne class 4 flavivirus responsible for several
human cases of haemorrhagic fever in Saudi Arabia, with no specific treatment
currently available. The viral RNA encodes a serine protease (NS2B-NS3),
essential for virus replication in infected cells, that constitutes an attractive
target for antiviral compounds. In an attempt to identify residues and motifs on
NS2B that are necessary for protease activity of the ALKV NS2B-NS3 complex, a
series of modified NS2B-NS3 proteins was constructed, with point mutations on
particular residues or with the NS2B domain derived from two different viruses.
Four mutants and the two chimeric proteins exhibited reduction of protease
activity against BAPNA (a p-nitroanilide substrate). The results demonstrate that
tight complementarity of the protein sequences is necessary for NS2B-dependent
activation of NS3. The results also determine residues in the ALKV NS2B cofactor
essential for protease activation, giving new insights into protease function in
flaviviruses.
PMID- 17030862
TI - Identification of Japanese encephalitis virus-inducible genes in mouse brain and
characterization of GARG39/IFIT2 as a microtubule-associated protein.
AB - Several mouse central nervous system genes have been identified that are
differentially regulated during Japanese encephalitis virus (JEV) infection,
including those which have not been reported to be induced by any other
neurotropic virus. Interestingly, approximately 80 % of JEV-inducible genes
identified in this study are also induced by Sindbis virus, indicating activation
of common host signalling pathways by these two viruses, despite their diverse
life cycles. One of these, the glucocorticoid attenuated response gene 39
(GARG39, also known as IFIT2, ISG54 and MuP54) was characterized further. It was
demonstrated that GARG39 protein interacts with microtubules in vitro, co
localizes with beta-tubulin in vivo and is enriched in the mitotic spindle of non
neuronal cells undergoing mitosis. While GARG39 was known for a long time as an
inflammation-inducible glucocorticoid attenuated protein, its identification as a
microtubule-associated protein in this study suggests a possible role for this
protein in cell proliferation, virion assembly/transport and microtubule
dynamics.
PMID- 17030863
TI - Secondary structure of dengue virus type 4 3' untranslated region: impact of
deletion and substitution mutations.
AB - Several studies have generated computer-based predictions of secondary structure
of the 3' untranslated region (UTR) of Dengue virus (DEN); however, experimental
verification of the formation of these structures in vitro is lacking. This study
assessed the congruence of Mfold predictions of secondary structure of the core
region of the DEN type 4 3' UTR with nuclease maps of this region. Maps and
predictions were largely consistent. Maps supported the existence of previously
predicted pseudoknots and identified putative regions of dynamic folding.
Additionally, this study investigated previously identified conserved elements in
the flavivirus 3' UTR that differ among viruses with different modes of
transmission. Specific regions of mosquito-borne DEN type 4 were either deleted
or replaced with homologous sequences from tick-borne Langat virus. All of these
mutations caused substantial distortion of secondary structure, yet viruses
carrying these mutations were viable.
PMID- 17030864
TI - Direct repeats in the 3' untranslated regions of mosquito-borne flaviviruses:
possible implications for virus transmission.
AB - Direct repeats (DRs) of 20-45 nucleotide conserved sequences (CS) and repeated CS
(RCS), separated by non-conserved sequences up to 100 nucleotides long, were
previously described in the 3' untranslated region (3'UTR) of the three major
mosquito-borne flavivirus (MBFV) subgroups, represented by Japanese encephalitis
virus, Yellow fever virus and Dengue virus. Each subgroup exhibits a specific
pattern of DRs, the biological significance of which has not yet been adequately
addressed. The DRs were originally identified using conventional alignment
programs based on the assumption that genetic variation is driven primarily by
nucleotide substitutions. Since there are no recognized alignment programs that
can adequately accommodate very divergent sequences, a method has been devised to
construct and analyse a substantially improved 3'UTR alignment between these
highly divergent viruses, based on the concept that deletions and/or insertions,
in addition to substitutions, are important drivers of 3'UTR evolution. This
'robust alignment' approach demonstrated more extensive homologies in the 3'UTR
than had been recognized previously and revealed the presence of similar DRs,
either intact or as sequence 'remnants', in all the MBFV subgroups. The relevance
of these observations is discussed in relation to (i) the function of DRs as
elements of replication enhancement, (ii) the evolution of RNA secondary
structures and (iii) the significance of DRs and secondary structures in MBFV
transmissibility between vertebrate and invertebrate hosts.
PMID- 17030865
TI - Molecular analysis of duck hepatitis virus type 1 reveals a novel lineage close
to the genus Parechovirus in the family Picornaviridae.
AB - Duck hepatitis virus type 1 (DHV-1) was previously classified as an enterovirus,
based primarily on observed morphology and physicochemical properties of the
virion. The complete nucleotide sequences of two strains (DRL-62 and R85952) of
DHV-1 have been determined. Excluding the poly(A) tail, the genomes are 7691 and
7690 nt, respectively, and contain a single, large open reading frame encoding a
polyprotein of 2249 aa. The genome of DHV-1 is organized as are those of members
of the family Picornaviridae: 5' untranslated region (UTR)-VP0-VP3-VP1-2A1-2A2-2B
2C-3A-3B-3C-3D-3' UTR. Analysis of the genomic and predicted polyprotein
sequences revealed several unusual features, including the absence of a predicted
maturation cleavage of VP0, the presence of two unrelated 2A protein motifs and a
3' UTR extended markedly compared with that of any other picornavirus. The 2A1
protein motif is related to the 2A protein type of the genus Aphthovirus and the
adjacent 2A2 protein is related to the 2A protein type present in the genus
Parechovirus. Phylogenetic analysis using the 3D protein sequence shows that the
two DHV-1 strains are related more closely to members of the genus Parechovirus
than to other picornaviruses. However, the two DHV-1 strains form a monophyletic
group, clearly distinct from members of the genus Parechovirus.
PMID- 17030866
TI - Quantitative analysis of poliomyelitis-like paralysis in mice induced by a
poliovirus replicon.
AB - Poliovirus (PV) infection causes severe paralysis, typically of the legs, by
destruction of the motor neurons in the spinal cord. In this study, the
relationship between PV replication in the spinal cord, damage in the motor
neurons and poliomyelitis-like paralysis was analysed in transgenic mice
expressing the human PV receptor (TgPVR21). First, a PV replicon encoding firefly
luciferase in place of the capsid genes (PV-Fluc mc) was trans-encapsidated in
293T cells and the trans-encapsidated PV-Fluc mc (TE-PV-Fluc mc) was then
inoculated into the spinal cords of TgPVR21 mice. TE-PV-Fluc mc was recovered
with a titre of 6.3 x 10(7) infectious units ml(-1), which was comparable to
those of PV1 strains. TgPVR21 mice inoculated with TE-PV-Fluc mc showed non
lethal paralysis of the hindlimbs, with severity ranging from a decline in grip
strength to complete flaccid paralysis. The replication of TE-PV-Fluc mc in the
spinal cord reached peak levels at 10 h post-inoculation (p.i.), followed by the
appearance of paralysis at as early as 12 h p.i., reaching a plateau at 16 h p.i.
Histological analysis showed a correlation between the lesion and the severity of
the clinical symptoms in most mice. However, severe paralysis could also be
observed with an apparently low lesion score, where as few as 5.3 x 10(2) motor
neurons (1.4 % of the susceptible cells in the lumbar cord) were infected by TE
PV-Fluc mc. These results indicate that PV replication in a small population of
the motor neurons was critical for severe residual poliomyelitis-like paralysis
in TgPVR21 mice.
PMID- 17030868
TI - Feline calicivirus replication: requirement for polypyrimidine tract-binding
protein is temperature-dependent.
AB - The interaction of host-cell nucleic acid-binding proteins with the genomes of
positive-stranded RNA viruses is known to play a role in the translation and
replication of many viruses. To date, however, the characterization of similar
interactions with the genomes of members of the family Caliciviridae has been
limited to in vitro binding analysis. In this study, Feline calicivirus (FCV) has
been used as a model system to identify and characterize the role of host-cell
factors that interact with the viral RNA. It was demonstrated that polypyrimidine
tract-binding protein (PTB) interacts specifically with the 5' sequences of the
FCV genomic and subgenomic RNAs. Using RNA interference it was shown that PTB is
required for efficient FCV replication in a temperature-dependent manner. siRNA
mediated knockdown of PTB resulted in a 15- to 100-fold reduction in virus titre,
as well as a concomitant reduction in viral RNA and protein synthesis at 32
degrees C. In addition, virus-induced cytopathic effect was significantly delayed
as a result of an siRNA-mediated reduction in PTB levels. A role for PTB in the
calicivirus life cycle was more apparent at temperatures above and below 37
degrees C, fitting with the hypothesis that PTB functions as an RNA chaperone,
potentially aiding the folding of RNA into functional structures. This is the
first functional demonstration of a host-cell protein interacting with a
calicivirus RNA.
PMID- 17030867
TI - Identification of the cleavage sites of sapovirus open reading frame 1
polyprotein.
AB - Sapovirus (SaV), a member of the family Caliciviridae, is a causative agent of
acute gastroenteritis in humans and swine and is currently divided into five
genogroups, GI-GV. The proteolytic processing of the SaV open reading frame 1
(ORF1) polyprotein with a human GII SaV Mc10 strain has recently been determined
and the products are arranged in the following order: NH(2)-p11-p28-p35 (NTPase)
p32-p14 (VPg)-p70 (Pro-Pol)-p60 (VP1)-COOH. The cleavage site between p14 (VPg)
and p70 (Pro-Pol) was identified as E(1055)/A(1056) by N-terminal amino acid
sequencing. To identify other cleavage sites, a series of GII SaV Mc10 full
length clones containing disrupted potential cleavage sites in the ORF1
polyprotein were constructed and used to generate linear DNA templates for in
vitro coupled transcription-translation. The translation products were analysed
by SDS-PAGE or by immunoprecipitation with region-specific antibodies. N-terminal
amino acid sequencing with Escherichia coli-expressed recombinant proteins was
also used to identify the cleavage site between p32 and p14. These approaches
enabled identification of the six cleavage sites of the Mc10 ORF1 polyprotein as
E(69)/G(70), Q(325)/G(326), Q(666)/G(667), E(940)/A(941), E(1055)/A(1056) and
E(1722)/G(1723). The alignment of the SaV full-length ORF1 amino acid sequences
indicated that the dipeptides used for the cleavage sites were either E or Q at
the P1 position and A, G or S at the P1' position, which were conserved in the
GI, GII, GIII, GIV and GV SaV ORF1 polyprotein.
PMID- 17030869
TI - Inter- and intra-variant genetic heterogeneity of human coronavirus OC43 strains
in France.
AB - Human coronavirus OC43 (HCoV-OC43) causes acute, self-limited respiratory
infections. A close relationship between bovine coronaviruses (BCoVs) and HCoV
OC43 has recently been demonstrated. This study includes seven clinical, non-cell
culture-adapted, contemporary HCoV-OC43 strains detected in France in 2003. By
using RT-PCR and clonal sequencing of the S1 gene of HCoV-OC43, the inter-variant
heterogeneity of the HCoV-OC43 circulating strains was studied and the intra
variant diversity was assessed by investigation of a quasispecies cloud. This
paper brings to the forefront a high genetic diversity of circulating HCoV-OC43
variants. Genetically different groups are defined among the variants described
in this study. One of these variants holds characteristics of an outlier and
presents a deletion of 12 nt, also found in BCoV strains. Moreover, the presence
of HCoV-OC43 as a quasispecies cloud in vivo during an acute respiratory-tract
illness was discovered. It has also been revealed that quasispecies-cloud sizes
are similar for the two viral populations tested.
PMID- 17030870
TI - Full-length genome sequences of two SARS-like coronaviruses in horseshoe bats and
genetic variation analysis.
AB - Bats were recently identified as natural reservoirs of SARS-like coronavirus (SL
CoV) or SARS coronavirus-like virus. These viruses, together with SARS
coronaviruses (SARS-CoV) isolated from human and palm civet, form a distinctive
cluster within the group 2 coronaviruses of the genus Coronavirus, tentatively
named group 2b (G2b). In this study, complete genome sequences of two additional
group 2b coronaviruses (G2b-CoVs) were determined from horseshoe bat Rhinolophus
ferrumequinum (G2b-CoV Rf1) and Rhinolophus macrotis (G2b-CoV Rm1). The bat G2b
CoV isolates have an identical genome organization and share an overall genome
sequence identity of 88-92 % among themselves and between them and the
human/civet isolates. The most variable regions are located in the genes encoding
nsp3, ORF3a, spike protein and ORF8 when bat and human/civet G2b-CoV isolates are
compared. Genetic analysis demonstrated that a diverse G2b-CoV population exists
in the bat habitat and has evolved from a common ancestor of SARS-CoV.
PMID- 17030871
TI - Enhanced antiviral antibody secretion and attenuated immunopathology during
influenza virus infection in nitric oxide synthase-2-deficient mice.
AB - NOS2 gene-deficient (NOS2(-/-)) mice are less susceptible than wild-type
(NOS2(+/+)) mice to infection with Influenza A virus. Virus titres in the lungs
of influenza-infected NOS2(-/-) mice are significantly lower than those in
NOS2(+/+) mice, with enhanced viral clearance in NOS2(-/-) mice dependent on
gamma interferon (IFN-gamma). The current study was undertaken to ascertain the
role of specific components of the immune response in promoting virus clearance
in influenza-infected NOS2(-/-) mice. Levels of T cell- and natural killer cell
mediated cytotoxicity in the lungs of virus-infected mice were not significantly
different between NOS2(+/+) and NOS2(-/-) mice. However, virus-infected NOS2(-/-)
mice produced higher levels of virus-specific IgG2a antibody. Furthermore, more
viable B cells and plasmablasts, along with greater levels of IFN-gamma, were
found in NOS2(-/-) splenocyte cultures stimulated with B-cell mitogens. In
addition to the early reduction in virus titres, clinical symptoms and
proinflammatory cytokine production were attenuated in NOS2(-/-) mice. Thus,
NOS2(-/-) B cells are capable of responding rapidly to influenza virus infection
by proliferating and preferentially producing antibody of the IgG2a subtype. The
relationship between viral load and the development of immunopathology is
discussed.
PMID- 17030872
TI - Role of the influenza virus heterotrimeric RNA polymerase complex in the
initiation of replication.
AB - Both transcription and replication of the influenza virus RNA genome are
catalysed by a virus-specific RNA polymerase. Recently, an in vitro assay, based
on the synthesis of pppApG, for the initiation of replication by recombinant RNA
polymerase in the absence of added primer was described. Here, these findings are
extended to show that adenosine, AMP and ADP can each substitute for ATP in
reactions catalysed by either recombinant ribonucleoprotein or RNA polymerase
complexes with either model virion RNA (vRNA) or cRNA promoters. The use of
either adenosine or AMP, rather than ATP, provides a convenient, sensitive and
easy assay of replication initiation. Moreover, no pppApG was detected when a PB1
PA dimer, rather than the trimeric polymerase, was used to catalyse synthesis,
contrasting with a previous report using baculovirus-expressed influenza RNA
polymerase. Overall, it is suggested that the heterotrimeric polymerase is
essential for the initiation of replication.
PMID- 17030873
TI - Matrix protein of Vesicular stomatitis virus harbours a cryptic mitochondrial
targeting motif.
AB - Vesicular stomatitis virus (VSV) is a rhabdovirus that has attracted attention of
late as an oncolytic virus and as a vaccine vector. Mutations in the matrix (M)
gene of VSV yield attenuated strains that may be very useful in both settings. As
a result of this interest in the M protein, this study analysed various M-green
fluorescent protein (GFP) fusion constructs. Remarkably, fusion of the N terminus
of the M protein to GFP targeted the fluorescent protein to the surface of
mitochondria. Mutational analysis indicated that a mitochondrial-targeting motif
exists within aa 33-67. Expression of these fusion proteins led to loss of
mitochondrial membrane permeability and to an alteration in mitochondrial
organization mirroring that seen during viral infection. In addition, a portion
of the M protein present in infected cells co-purified with mitochondria. This
work may indicate a novel function for this multifunctional viral protein.
PMID- 17030874
TI - Identification of a cytotoxic T-lymphocyte (CTL) epitope recognized by Gag
specific CTLs in cynomolgus monkeys infected with simian/human immunodeficiency
virus.
AB - Infection of Macaca fascicularis (cynomolgus monkey) with chimeric simian/human
immunodeficiency virus (SHIV) provides a valuable experimental animal model of
AIDS and is widely used for the development of human immunodeficiency virus
vaccine strategies. In these settings, analysis of CD8(+) T-cell responses during
infection represents one of the key parameters for monitoring the evaluation of
containment of virus replication. The generation of Gag-specific CD8(+) T cells
was reported previously from a cynomolgus monkey infected with SHIV89.6P by
taking advantage of a B-lymphoblastoid cell line transduced with a retroviral
vector expressing simian immunodeficiency virus (SIV) Gag. Here, it was shown
that these cytotoxic T lymphocytes (CTLs) demonstrated specificity for a single 9
aa peptide (NCVGDHQAA) spanning aa 192-200 of the SIVmac239 p55(gag) protein.
Furthermore, a positive response was found against the same epitope in one of six
other SHIV-infected monkeys. This newly identified SIV Gag CTL epitope in SHIV
infected cynomolgus monkeys will be a useful tool for monitoring and evaluating
Gag-specific immune responses during vaccination and infection in the cynomolgus
monkey model of AIDS.
PMID- 17030875
TI - Identification of an HLA-A*0201-restricted cytotoxic T-lymphocyte epitope in
rotavirus VP6 protein.
AB - The function of cytotoxic T lymphocytes (CTLs) in rotavirus (RV) infection in
humans is poorly understood. To date, no RV-specific human leukocyte antigen
(HLA) class I-restricted T-cell epitopes have been described. In this study, four
peptides derived from human RV Wa strain VP6 protein were predicted by computer
algorithms and verified by an HLA*0201-binding assay. Two peptides with high
affinity for HLA-A*0201 molecules were further assessed. The CTLs induced in
vitro by P340-348 (TLLANVTAV)-loaded autologous dendritic cells from peripheral
blood lymphocytes of HLA-A*0201-matched healthy donors released gamma interferon
specifically upon stimulation with P340-348-loaded T2 cells. The CTLs lysed both
P340-348-loaded T2 cells and human RV Wa strain-infected HLA-A*0201(+) Caco-2
cells in an antigen-specific and HLA-A*0201-restricted manner. At the same time,
P340-348 was shown to be immunogenic in vivo in HLA-A*0201/Kb transgenic mice. It
is proposed that P340-348 is an HLA-A*0201-restricted CTL epitope.
PMID- 17030876
TI - The 5' non-translated region of Varroa destructor virus 1 (genus Iflavirus):
structure prediction and IRES activity in Lymantria dispar cells.
AB - Structure prediction of the 5' non-translated region (NTR) of four iflavirus RNAs
revealed two types of potential internal ribosome entry site (IRES), which are
discriminated by size and level of complexity, in this group of viruses. In
contrast to the intergenic IRES of dicistroviruses, the potential 5' IRES
structures of iflaviruses do not have pseudoknots. To test the activity of one of
these, a bicistronic construct was made in which the 5' NTR of Varroa destructor
virus 1 (VDV-1) containing a putative IRES was cloned in between two reporter
genes, enhanced green fluorescent protein and firefly luciferase (Fluc). The
presence of the 5' NTR of VDV-1 greatly enhanced the expression levels of the
second reporter gene (Fluc) in Lymantria dispar Ld652Y cells. The 5' NTR was
active in a host-specific manner, as it showed lower activity in Spodoptera
frugiperda Sf21 cells and no activity in Drosophila melanogaster S2 cells.
PMID- 17030877
TI - An iterated sequence in the genome of Banana bunchy top virus is essential for
efficient replication.
AB - Banana bunchy top virus (BBTV) has a multi-component genome of circular, single
stranded DNA. BBTV replicates via a rolling-circle mechanism, probably involving
sequence-specific interaction of the replication initiation protein (Rep) with
iterated sequences (iterons) within the viral genome. Three putative iterons
(designated F1, F2 and R), with the sequence GGGAC, have been identified in the
intergenic region of each BBTV component. To investigate their role in
replication, each of the iterons was mutated, singularly and in tandem, in a BBTV
DNA-N 1.1mer and the ability of these molecules to be replicated by the BBTV
'master' Rep was evaluated in banana cells using transient biolistic assays. All
iteron mutants were replicated less efficiently than the native DNA-N. Mutation
of the F1 and R iterons caused a 42 and 62 % reduction in DNA-N replication,
respectively, whereas mutation of the F2 and combined F1F2 iteron virtually
abolished DNA-N replication.
PMID- 17030878
TI - Production of plum pox virus HC-Pro functionally active for aphid transmission in
a transient-expression system.
AB - Potyviruses are non-persistently transmitted by aphid vectors with the assistance
of a viral accessory factor known as helper component (HC-Pro), a multifunctional
protein that is also involved in many other essential processes during the virus
infection cycle. A transient Agrobacterium-mediated expression system was used to
produce Plum pox virus (PPV) HC-Pro in Nicotiana benthamiana leaves from
constructs that incorporated the 5' region of the genome, yielding high levels of
HC-Pro in agroinfiltrated leaves. The expressed PPV HC-Pro was able to assist
aphid transmission of purified virus particles in a sequential feeding assay, and
to complement transmission-defective variants of the virus. Also, HC-Pro of a
second potyvirus, Tobacco etch virus (TEV), was expressed and found to be
functional for aphid transmission. These results show that this transient system
can be useful for production of functionally active HC-Pro in potyviruses, and
the possible uses of this approach to study the mechanism of transmission are
discussed.
PMID- 17030879
TI - Arabidopsis tonoplast proteins TIP1 and TIP2 interact with the cucumber mosaic
virus 1a replication protein.
AB - The cucumber mosaic virus (CMV) replication complex has previously been shown to
associate with cellular membranes. However, it remains unknown whether any host
factors participate in this process. In this study, five groups of Arabidopsis
tonoplast intrinsic protein (TIP) genes were isolated and the proteins they
encoded were evaluated with regard to their interactions with CMV proteins. TIP1
and TIP2 were found to interact with the CMV 1a protein in the Sos recruitment
system, whereas no interactions with the other three TIP subgroups were observed
in this assay. The interaction of CMV 1a with the TIP1 and TIP2 proteins was
confirmed via co-immunoprecipitation assays. Additionally, CMV 1a co-localized
with TIP1 and TIP2 in transfected Arabidopsis protoplasts. The findings of this
study suggest that members of two TIP subfamilies might affect CMV replication
via interaction with CMV 1a in the tonoplasts.
PMID- 17030880
TI - Phylogeography of Ustilago maydis virus H1 in the USA and Mexico.
AB - Ustilago maydis virus H1 (Umv-H1) is a mycovirus that infects Ustilago maydis, a
fungal pathogen of maize. As Zea mays was domesticated, it carried with it many
associated symbionts, such that the subsequent range expansion and cultivation of
maize should have affected maize symbionts' evolutionary history dramatically.
Because transmission of Umv-H1 takes place only through cytoplasmic fusion during
mating of U. maydis individuals, the population dynamics of U. maydis and maize
are expected to affect the population structure of the viral symbiont strongly.
Here, the impact of changes in the evolutionary history of U. maydis on that of
Umv-H1 was investigated. The high mutation rate of this virus allows inferences
to be made about the evolution and divergence of Umv-H1 lineages as a result of
the recent changes in U. maydis geographical and genetic structure. The
phylogeographical history and genetic structure of Umv-H1 populations in the USA
and Mexico were determined by using analyses of viral nucleotide sequence
variation. Infection and recombination frequencies, genetic diversity and rates
of neutral evolution were also assessed, to make inferences regarding
evolutionary processes underlying the population genetic structure of ancestral
and descendent populations. The results suggest that Mexico represents the
ancestral population of Umv-H1, from which the virus has been carried with U.
maydis populations into the USA. Thus, the population dynamics of one symbiont
represent a major evolutionary force on the co-evolutionary dynamics of symbiotic
partners.
PMID- 17030881
TI - Prion protein in cardiac muscle of elk (Cervus elaphus nelsoni) and white-tailed
deer (Odocoileus virginianus) infected with chronic wasting disease.
AB - To investigate the possible presence of disease-associated prion protein (PrP(d))
in striated muscle of chronic wasting disease (CWD)-affected cervids, samples of
diaphragm, tongue, heart and three appendicular skeletal muscles from mule deer
(Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), elk (Cervus
elaphus nelsoni) and moose (Alces alces shirasi) were examined by ELISA, Western
immunoblot and immunohistochemistry (IHC). PrP(d) was detected in samples of
heart muscle from seven of 16 CWD-infected white-tailed deer, including one free
ranging deer, and in 12 of 17 CWD-infected elk, but not in any of 13 mule deer
samples, nor in the single CWD-infected moose. For white-tailed deer, PrP(d) was
detected by Western blot at multiple sites throughout the heart; IHC results on
ventricular sections of both elk and white-tailed deer showed positive staining
in cardiac myocytes, but not in conduction tissues or nerve ganglia. Levels of
PrP(d) in cardiac tissues were estimated from Western blot band intensity to be
lower than levels found in brain tissue. PrP(d) was not detected in diaphragm,
triceps brachii, semitendinosus, latissiumus dorsi or tongue muscles for any of
the study subjects. This is the first report of PrP(d) in cardiac tissue from
transmissible spongiform encephalopathy-infected ruminants in the human food
chain and the first demonstration by immunological assays of PrP(d) in any
striated muscle of CWD-infected cervids.
PMID- 17030882
TI - Patterns of PrPCWD accumulation during the course of chronic wasting disease
infection in orally inoculated mule deer (Odocoileus hemionus).
AB - Patterns of abnormal prion protein (PrP) accumulation during the course of
chronic wasting disease (CWD) infection were studied and the distribution and
timing of disease-associated PrP (PrP(CWD)) deposition and lesions in 19 mule
deer (Odocoileus hemionus) 90-785 days after oral inoculation were described.
PrP(CWD) deposition occurred relatively rapidly and widely in lymphoid tissues,
later in central and peripheral nervous tissues and sporadically in a variety of
tissues and organs in terminal disease stages. Development of spongiform
encephalopathy lagged behind PrP(CWD) deposition in the central nervous system
(CNS), but occurred in the same neuroanatomical locations. PrP(CWD) deposition in
the lymphatic and nervous systems tended to be consistent and progressive in
specific organs and tissues. Locations of PrP(CWD) deposition were similar
between deer of two PrP genotypes (225SS and 225SF), but the time course differed
between genotypes: in 225SF deer, PrP(CWD) accumulated more slowly in lymphatic
tissues than in 225SS animals, but that disparity was small in comparison to the
disparity between genotypes in timing of deposition in CNS tissue. These data
confirm retropharyngeal lymph node and medulla oblongata at the level of the obex
as early sites of PrP(CWD) accumulation in mule deer with CWD. Data on the
relative time frames for and genetic influences on PrP(CWD) accumulation may also
offer insights about epidemic dynamics and potential control strategies.
PMID- 17030883
TI - Lymphoid follicles of the ileal Peyer's patch of lambs express low levels of PrP,
as demonstrated by quantitative real-time RT-PCR on microdissected tissue
compartments, in situ hybridization and immunohistochemistry.
AB - The expression level of normal cellular prion protein (PrP(C)) is thought to
influence the transmission of transmissible spongiform encephalopathies (TSEs)
from the peripheral entry site to the site of pathological changes in the central
nervous system. In many TSEs, the clinical disease is preceded by a period in
which the agent accumulates in lymphoid organs, particularly in association with
follicular dendritic cells of lymphoid follicles. As the probable route of entry
of the TSE agent is via the gut, the expression profile of PrP was examined in
well-developed gut-associated lymphoid tissue of lambs, the ileal Peyer's patch,
by laser microdissection and real-time RT-PCR. Lymphoid follicles were found to
have very low levels of expression, whilst highest levels were detected in the
outer submucosa and the muscular layer. These findings were supported by in situ
hybridization and immunohistochemistry, which showed specific labelling in nerve
cells in ganglia of the submucosal (Meissner's) and myenteric (Auerbach's) plexi
of the enteric nervous system. Based on the assumption that potential sites for
conversion to the scrapie-related prion protein (PrP(Sc)) should display high
levels of expression of PrP(C), this study suggests that the accumulation of
PrP(Sc) in the lymphoid follicles of the Peyer's patch is not preceded by PrP
conversion in the same tissue compartment.
PMID- 17030884
TI - Congruence and functions of personal and cultural values: do my values reflect my
culture's values?
AB - Two studies are described examining the correlation between self- and culture
referenced values at a culture level (Study 1) and correlation between self- and
culture-referenced values and self-reported behavior at an individual level
(Study 2). It is found that values related to individual-group relationships
(embeddedness) and expression and experience of affective feelings and emotions
(affective autonomy) are significantly correlated at a culture level. In Study 2,
culture-referenced values are shown to correlate with behaviors attached to
social norms, whereas self-rated values are found to correlate with behaviors
that are not norm-governed. Implications for measurement of cultural values and
cultural and cross-cultural research designs are discussed.
PMID- 17030885
TI - Why are attributions to discrimination interpersonally costly? A test of system-
and group-justifying motivations.
AB - In two studies, Whites' endorsement of system-justifying beliefs predicted
increased negativity toward Blacks who blamed negative events on discrimination.
Whites' system-justifying beliefs were not associated with negativity toward
Blacks who blamed negative events on other internal causes, external causes, or
nondiscriminatory unfairness. These negative reactions toward discrimination
claimants were mediated by perceptions that the claimant held dissimilar values
and failed to take personal responsibility for outcomes. In both studies,
participants' White Identification did not moderate the relationship between the
Black target's attribution for failure and subsequent negative perceptions of
that individual, thus providing evidence against a group-justification
explanation of these findings.
PMID- 17030886
TI - A novel approach to assessing achievement goals in the context of the 2 x 2
framework: identifying distinct profiles of individuals with different dominant
achievement goals.
AB - In two studies, individuals' dominant achievement goals were assessed using a
new, simple, and conceptually precise measure based on Elliot and McGregor's
(2001) 2 x 2 framework. Next, the four groups were compared in terms of
achievement-relevant variables, including need for achievement, perfectionism,
perceived competence, interest, and graded performance. As expected, a very high
percentage (approximately 85%) of people indicated they had a dominant
achievement goal. Furthermore, the results suggest that individuals with
different dominant achievement goals have clear, distinct profiles that can be
characterized as positively valenced (mastery-approach), both positively and
negatively valenced (performance-approach), negatively valenced (performance
avoidance), or neither positively nor negatively valenced (mastery-avoidance).
PMID- 17030887
TI - What you want (and do not want) affects what you see (and do not see): avoidance
social goals and social events.
AB - Two studies examined the influence of approach and avoidance social goals on
memory for and evaluation of ambiguous social information. Study 1 found that
individual differences in avoidance social goals were associated with greater
memory of negative information, negatively biased interpretation of ambiguous
social cues, and a more pessimistic evaluation of social actors. Study 2
experimentally manipulated social goals and found that individuals high in
avoidance social motivation remembered more negative information and expressed
more dislike for a stranger in the avoidance condition than in the approach
condition. Results suggest that avoidance social goals are associated with
emphasizing potential threats when making sense of the social environment.
PMID- 17030888
TI - The effects of a parenting prime on sex differences in mate selection criteria.
AB - This study tested an evolutionary hypothesis that the mere prospect of caring for
a child will increase sex differences in human mate selection criteria. That is,
women would adopt a stronger preference for socially dominant men when parenting
had been primed and men would adopt a stronger preference for physically
attractive women when parenting had been primed. Male and female university
students were randomly assigned to be exposed to a parenting prime or a
nonparenting prime. Following the priming procedure, participants rated the
romantic appeal of a target person of the opposite sex. Exposure to the parenting
prime, the target's social dominance, and the target's physical attractiveness
were orthogonally manipulated. As predicted, women adopted a stronger mate
preference for social dominance when parenting was at the forefront of the mind.
Contrary to predictions, the parenting prime had no effect on men's mate
preference for physical attractiveness.
PMID- 17030889
TI - Conformism moderates the relations between values, anticipated regret, and
behavior.
AB - The purpose of the present study was to evaluate the moderating effect of
Conformism values on the relations between other values and behavior. The authors
expected people low, but not high, in Conformism to behave in a manner that is
consistent with their personal values related to self-transcendence versus self
enhancement. In Study 1 (N = 199), such values predicted actual altruistic
behavior, as estimated by other-reports, but only if Conformism values were low.
In Study 2 (N = 189), only people who considered Conformism values to be
relatively unimportant showed expected connections between self-transcendence
values and anticipated regret in hypothetical scenarios having negative
consequences. The data are interpreted as supporting the view that (a)
anticipated regret motivates value-consistent behavior, (b) self-transcendence
values in particular are connected to altruistic behavior and to anticipated
regret, but (c) conformity to social norms moderates these connections.
PMID- 17030890
TI - The effect of age and role information on expectations for big five personality
traits.
AB - In four studies, the authors investigated the extent to which expectations for
personality traits in age-graded roles correspond to patterns of personality
trait change across the life course. In Studies 1 (N = 43) and 2 (N = 126), the
authors examined the age-graded roles of high school student, college student,
parent, and grandparent and found that expectations for how people behave in
these age-graded roles showed strong parallels to the documented pattern of
personality trait development and that this pattern of expectations was largely
shared by younger and older participants. In Studies 3 (N = 252) and 4 (N = 123),
the authors separated age and role information (e.g., marital, parental, and
employment status) and found that people use both sources of information
independently in forming expectations of others. The implications for
understanding the interplay of expectations and personality trait development are
discussed.
PMID- 17030891
TI - Voicing conflict: preferred conflict strategies among incremental and entity
theorists.
AB - The way individuals choose to handle their feelings during interpersonal
conflicts has important consequences for relationship outcomes. In this article,
the authors predict and find evidence that people's implicit theory of
personality is an important predictor of conflict behavior following a
relationship transgression. Incremental theorists, who believe personality can
change and improve, were likely to voice their displeasure with others openly and
constructively during conflicts. Entity theorists, who believe personality is
fundamentally fixed, were less likely to voice their dissatisfactions directly.
These patterns were observed in both a retrospective study of conflict in dating
relationships (Study 1) and a prospective study of daily conflict experiences
(Study 2). Study 2 revealed that the divergence between incremental and entity
theorists was increasingly pronounced as conflicts increased in severity: the
higher the stakes the stronger the effect.
PMID- 17030892
TI - Childhood physical and emotional abuse by a parent: transference effects in adult
interpersonal relations.
AB - Extending research on transference and the relational self (Andersen & Chen,
2002), female undergraduates with or without a history of physical and emotional
abuse by a loved parent participated in an experiment manipulating parental
resemblance and threat-relevant interpersonal context in a new person.
Transference elicited differences not evident in the control condition between
abused and nonabused participants' responses, with greater rejection expectancy,
mistrust, dislike, and emotional indifference reported by abused participants.
Immediate implicit affect was more positive in transference than in the control
condition regardless of abuse history. Yet, abused participants in transference
also reported increased dysphoria that was markedly attenuated when interpersonal
threat was primed, and no such pattern occurred among nonabused participants.
Evidence that interpersonally guarded and affectively complex responses are
triggered in transference among previously abused individuals suggests that this
social-cognitive process may underlie long-term interpersonal difficulties
associated with parental abuse.
PMID- 17030893
TI - The role of perceived similarity in supportive responses to victims of negative
life events.
AB - The authors examined whether participants' perceived similarity to an ostensible
victim of a negative life event influenced their supportiveness during a live
interaction. Two competing models were considered: (a) increased similarity would
be associated with increased supportiveness through attraction to the target and
(b) increased similarity would be associated with decreased supportiveness
through anxiety (due to heightened vulnerability). Participants (N = 241) met
individually with a confederate posing as a cancer patient. Reactions were
assessed, including verbal and nonverbal behaviors, both before and after the
interaction, by participants themselves and by observers of the interaction.
Results supported a model based on the classic similarity/attraction paradigm:
Perceived similarity indirectly predicted participant-reported
supportiveness/warmth and smiling through its relationship to attraction. Results
extend the literature on similarity and attraction to the stress and coping arena
and suggest that emphasizing perceived similarities to victims would be
beneficial.
PMID- 17030894
TI - Bolstering implementation plans for the long haul: the benefits of simultaneously
boosting self-concordance or self-efficacy.
AB - Recent studies suggest that implementation planning exercises may not be as
helpful for long-term, self-initiated goals as for short-term, assigned goals.
Two studies used the personal goal paradigm to explore the impact of
implementation plans on goal progress over time. Study 1 examined whether
administering implementation plans in an autonomy supportive manner would
facilitate goal progress relative to a neutral, control condition and a condition
in which implementation plans were administered in a controlling manner. Study 2
examined whether combining implementation plans with a self-efficacy boosting
exercise would facilitate goal progress relative to a neutral, control condition
and a typical implementation condition. The results showed that implementation
plans alone did not result in greater goal progress than a neutral condition but
that the combination of implementation plans with either autonomy support or self
efficacy boosting resulted in significantly greater goal progress.
PMID- 17030895
TI - Group morality and intergroup relations: cross-cultural and experimental
evidence.
AB - An observational, cross-cultural study and an experimental study assessed
behaviors indicative of a moral code that condones, and even values, hostility
toward outgroups. The cross-cultural study, which used data from the Standard
Cross-Cultural Sample (Murdock & White, 1969), found that for preindustrial
societies, as loyalty to the ingroup increased the tendency to value outgroup
violence more than ingroup violence increased, as did the tendencies to engage in
more external than internal warfare, and enjoy war. The experimental study found
that relative to guilt-prone group members who were instructed to remain
objective, guilt-prone group members who were instructed to be empathic with
their ingroup were more competitive in an intergroup interaction. The findings
from these studies suggest that group morality is associated with intergroup
conflict.
PMID- 17030896
TI - Taste receptors in the gastrointestinal tract. II. L-amino acid sensing by
calcium-sensing receptors: implications for GI physiology.
AB - The extracellular calcium-sensing receptor (CaR) is a multimodal sensor for
several key nutrients, notably Ca2+ ions and L-amino acids, and is expressed
abundantly throughout the gastrointestinal tract. While its role as a Ca2+ ion
sensor is well recognized, its physiological significance as an L-amino acid
sensor and thus, in the gastrointestinal tract, as a sensor of protein ingestion
is only now coming to light. This review focuses on the CaR's amino acid sensing
properties at both the molecular and cellular levels and considers new and
putative physiological roles for the CaR in the amino acid-dependent regulation
of gut hormone secretion, epithelial transport, and satiety.
PMID- 17030897
TI - Differentiation of the gastric mucosa. II. Role of gastrin in gastric epithelial
cell proliferation and maturation.
AB - Gastrin is the principal hormonal inducer of gastric acid secretion. The cellular
targets for gastrin in the stomach are the acid-secreting parietal cell and
histamine-producing enterochromaffin-like (ECL) cell. Gastrin is also a growth
factor, with hypergastrinemia resulting in increased proliferation of gastric
progenitor cells and a thickened mucosa. This review presents insights into
gastrin function revealed by genetically engineered mouse models, demonstrating a
new role for gastrin in the maturation of parietal and ECL cells. Thus, gastrin
regulates many aspects of gastric physiology, with tight regulation of gastrin
levels required to maintain balanced growth and function of gastric epithelial
cells.
PMID- 17030898
TI - IL-10 protects mouse intestinal epithelial cells from Fas-induced apoptosis via
modulating Fas expression and altering caspase-8 and FLIP expression.
AB - We have previously shown that the absence of Fas/Fas ligand significantly reduced
tissue damage and intestinal epithelial cell (IEC) apoptosis in an in vivo model
of T cell-mediated enteropathy. This enteropathy was more severe in IL-10
deficient mice, and this was associated with increased serum levels of IFN-gamma
and TNF-alpha and an increase in Fas expression on IECs. In this study, we
investigated the potential of IL-10 to directly influence Fas expression and Fas
induced IEC apoptosis. Mouse intestinal epithelial cell lines MODE-K and IEC4.1
were cultured with IFN-gamma, TNF-alpha, or anti-Fas monoclonal antibody (mAb) in
the presence or absence of IL-10. Fas expression and apoptosis were determined by
FACScan analysis of phycoerythrin-anti-Fas mAb staining and annexin V staining,
respectively. Treatment with a combination of IFN-gamma and TNF-alpha induced
significant apoptosis. Anti-Fas mAb alone did not induce much apoptosis unless
cells were pretreated with IFN-gamma and TNF-alpha. These IECs constitutively
expressed low levels of Fas, which significantly increased by preincubation of
the cells with IFN-gamma and TNF-alpha. Treatment with cytokine or cytokine plus
anti-Fas mAb increased apoptosis, which correlated with a decreased Fas
associated death domain IL-1-converting enzyme-like inhibitory protein (FLIP)
level, increased caspase-8 activity, and subsequently increased caspase-3
activity. IL-10 diminished both cytokine- and anti-Fas mAb-induced apoptosis, and
this was correlated with decreased cytokine-induced Fas expression, increased
FLIP, and decreased caspase-8 and caspase-3 activity. In conclusion, IL-10
modulated cytokine induction of Fas expression on IEC cell lines and regulated
IEC susceptibility to TNF-alpha, IFN-gamma, and Fas-mediated apoptosis. These
findings suggest that IL-10 directly modulates IEC responses to T cell-mediated
apoptotic signals.
PMID- 17030899
TI - Interaction of complement and leukocytes in severe acute pancreatitis: potential
for therapeutic intervention.
AB - In acute pancreatitis, local as well as systemic organ complications are mediated
by the activation of various inflammatory cascades. The role of complement in
this setting is unclear. The aim of the present study was to determine the level
of complement activation in experimental pancreatitis, to evaluate the
interaction of complement and leukocyte-endothelium activation, and to assess the
effects of complement inhibition by soluble complement receptor 1 (sCR1) in this
setting. Necrotizing pancreatitis was induced in Wistar rats by the combination
of intravenous cerulein and retrograde infusion of glycodeoxycholic acid into the
biliopancreatic duct; edematous pancreatitis was induced by intravenous cerulein
only. In control animals, a sham operation (midline laparotomy) was performed.
Complement activation, leukocyte sequestration, and pancreatic as well as
pulmonary injury were assessed in the presence/absence of sCR1. Increased levels
of C3a were found in necrotizing but not in edematous pancreatitis. When
complement activation in necrotizing pancreatitis was blocked by sCR1, levels of
C3a and total hemolytic activity (CH50) were decreased. Leukocyte-endothelial
interaction, as assessed by intravital microscopy, and pancreatic as well as
pulmonary organ injury (wet-to-dry weight ratio, MPO activity, and histology)
were ameliorated by sCR1. As a result of the present study, necrotizing but not
edematous pancreatitis is characterized by significant and early complement
activation. Based on the interaction of complement and leukocytes, complement
inhibition by sCR1 may be a valuable option in the treatment of leukocyte
associated organ injury in severe pancreatitis.
PMID- 17030900
TI - Platelet-activating factor in the enteric nervous system of the guinea pig small
intestine.
AB - Platelet-activating factor (PAF) is a proinflammatory mediator that may influence
neuronal activity in the enteric nervous system (ENS). Electrophysiology,
immunofluorescence, Western blot analysis, and RT-PCR were used to study the
action of PAF and the expression of PAF receptor (PAFR) in the ENS. PAFR
immunoreactivity (IR) was expressed by 6.9% of the neurons in the myenteric
plexus and 14.5% of the neurons in the submucosal plexus in all segments of the
guinea pig intestinal tract as determined by double staining with anti-human
neuronal protein antibody. PAFR IR was found in 6.1% of the neurons with IR for
calbindin, 35.8% of the neurons with IR for neuropeptide Y (NPY), 30.6% of the
neurons with IR for choline acetyltransferase (ChAT), and 1.96% of the neurons
with IR for vasoactive intestinal peptide (VIP) in the submucosal plexus. PAFR IR
was also found in 1.5% of the neurons with IR for calbindin, 51.1% of the neurons
with IR for NPY, and 32.9% of the neurons with IR for ChAT in the myenteric
plexus. In the submucosal plexus, exposure to PAF (200-600 nM) evoked
depolarizing responses (8.2 +/- 3.8 mV) in 12.4% of the neurons with S-type
electrophysiological behavior and uniaxonal morphology and in 12.5% of the
neurons with AH-type electrophysiological behavior and Dogiel II morphology,
whereas in the myenteric preparations, depolarizing responses were elicited by a
similar concentration of PAF in 9.5% of the neurons with S-type
electrophysiological behavior and uniaxonal morphology and in 12.0% of the
neurons with AH-type electrophysiological behavior and Dogiel II morphology. The
results suggest that subgroups of secreto- and musculomotor neurons in the
submucosal and myenteric plexuses express PAFR. Coexpression of PAFR IR with ChAT
IR in the myenteric plexus and ChAT IR and VIP IR in the submucosal plexus
suggests that PAF, after release in the inflamed bowel, might act to elevate the
excitability of submucosal secretomotor and myenteric musculomotor neurons.
Enhanced excitability of motor neurons might lead to a state of neurogenic
secretory diarrhea.
PMID- 17030901
TI - Phospholipase D and extracellular signal-regulated kinase in hepatic stellate
cells: effects of platelet-derived growth factor and extracellular nucleotides.
AB - We have previously provided evidence suggesting that phosphatidic acid, possibly
derived from the hydrolysis of phosphatidylcholine by phospholipase D (PLD), is
involved in platelet-derived growth factor (PDGF)-mediated increases in
extracellular signal-regulated kinase (ERK) activity and DNA synthesis in rat
hepatic stellate cells (HSC), the primary fibrogenic cells of the liver. A recent
study has shown the presence of P2Y nucleotide receptors on HSC that are coupled
to contraction and synthesis of the matrix component, alpha1-procollagen, leading
to the suggestion that they may represent a new therapeutic target in the
treatment of liver fibrosis. However, although extracellular nucleotides have
been shown to stimulate both PLD and ERK, and to elicit proliferation of
fibrogenic cells outside the liver, their effect on these parameters in HSC have
not yet been investigated. PLD activity was determined by [3H]choline release and
[3H]phosphatidylbutanol production, ERK activity by Western blotting, and DNA
synthesis by [3H]thymidine incorporation. We report here, for the first time in
HSC, that extracellular nucleotides stimulate PLD activity and a sustained
activation of ERK. However, in contrast to PDGF, nucleotides had negligible
effects on DNA synthesis. Moreover, the effects of PDGF and nucleotides on PLD
and ERK were not additive, suggesting activation of the same PLD isoform and pool
of ERK. The data demonstrate that nucleotide-stimulated PLD and ERK activities
are not coupled to DNA synthesis in HSC. Instead, these responses may be linked
to other phenotypic changes associated with activated HSC such as increases in
contraction, motility, or extracellular matrix deposition.
PMID- 17030902
TI - An age-structured model of dendritic cell trafficking in the lung.
AB - As the sentinels of the immune system, dendritic cells (DC) play a critical role
in initiating and maintaining appropriate T cell responses through capture and
presentation of antigen, costimulation, and mediator release. Although much is
known about certain aspects of DC function, the exact relationship between lung
epithelial DC precursor populations in the blood and their functional role in
antigen presentation are not clearly understood. I created an age-structured
mathematical model for DC trafficking into the lung to address this question.
While capturing experimentally observed system dynamics, I found that blood DC
are preferentially recruited over blood monocytes. For short-lived antigens, the
model results suggest that lung epithelial DC derived from blood DC exhibit a
625% increase in antigen density compared with those derived from blood
monocytes. Finally, these results motivate future experimental studies to clarify
aspects of DC trafficking in the lung.
PMID- 17030903
TI - BMP-dependent activation of caspase-9 and caspase-8 mediates apoptosis in
pulmonary artery smooth muscle cells.
AB - Germ line mutations in the bone morphogenetic protein (BMP) receptor type II
(BMPRII) gene have been found in >50% of familial idiopathic pulmonary arterial
hypertension (IPAH) patients and in 30% of sporadic cases of IPAH. Mutations of
BMPRII occur in the extracellular ligand-binding domain, in the cytoplasmic
serine/threonine kinase domain, or in the long carboxy terminus domain of unknown
function. In this study, we demonstrate that BMPs promote apoptotic cell death in
normal human pulmonary artery smooth muscle cells (PASMCs) by activation of
caspases-3, -8, and -9, cytochrome c release, and downregulation of Bcl-2. Normal
PASMCs expressing a kinase domain mutant or a carboxy-terminal domain deletion
mutant of BMPRII identified in IPAH patients are resistant to BMP-mediated
apoptosis. This dominant-negative effect may act in heterozygous patients and
lead to the development of the pulmonary vascular medial hypertrophy found in
IPAH patients. Our study also demonstrates an essential role of the carboxy
terminus domain of BMPRII in the activation of the apoptotic signaling cascade.
PMID- 17030904
TI - Treatment of plague: promising alternatives to antibiotics.
AB - Plague still poses a significant threat to human health, and interest has been
renewed recently in the possible use of Yersinia pestis as a biological weapon by
terrorists. The septicaemic and pneumonic forms are always lethal if untreated.
Attempts to treat this deadly disease date back to the era of global pandemics,
when various methods were explored. The successful isolation of the plague
pathogen led to the beginning of more scientific approaches to the treatment and
cure of plague. This subsequently led to specific antibiotic prophylaxis and
therapy for Y. pestis. The use of antibiotics such as tetracycline and
streptomycin for the treatment of plague has been embraced by the World Health
Organization Expert Committee on Plague as the 'gold standard' treatment.
However, concerns regarding the development of antibiotic-resistant Y. pestis
strains have led to the exploration of alternatives to antibiotics. Several
investigators have looked into the use of alternatives, such as immunotherapy,
non-pathogen-specific immunomodulatory therapy, phage therapy, bacteriocin
therapy, and treatment with inhibitors of virulence factors. The alternative
therapies reported in this review should be further investigated by comprehensive
studies of their clinical application for the treatment of plague.
PMID- 17030905
TI - Mutation of luxS affects motility and infectivity of Helicobacter pylori in
gastric mucosa of a Mongolian gerbil model.
AB - Helicobacter pylori is associated with gastric disorders in humans and some
experimental animals, and possesses the luxS/type 2 autoinducer (AI-2) system.
The effects of a specific luxS mutation on the characteristics of H. pylori were
examined. On 0.3 % agar medium, motility of H. pylori HPKY08 (luxS : : cat) was
significantly lower than that of wild-type H. pylori TK1402. The luxS
complemented strain HPKY21 exhibited motility comparable to that of H. pylori
TK1402. It was shown that the luxS/AI-2 system plays an important role in H.
pylori motility. The luxS mutant exhibited a reduced infection rate relative to
the wild-type parent strain TK1402 in a Mongolian gerbil model. At 3 months after
oral inoculation, lower numbers of H. pylori were detected by semi-quantitative
real-time reverse transcription PCR (qRT-PCR) in luxS(-) mutant-infected gerbils
than in TK1402-infected gerbils. Gastric inflammation and increased antibody
titre for H. pylori were observed in TK1402-infected gerbils only.
PMID- 17030906
TI - Cytolethal distending toxins in Shiga toxin-producing Escherichia coli: alleles,
serotype distribution and biological effects.
AB - To assess the prevalence of cytolethal distending toxin (CDT) among Shiga toxin
producing Escherichia coli (STEC), 202 STEC strains were investigated using PCRs
targeting various cdt alleles (cdt-I to cdt-V). Seven of the 202 strains
contained cdt-III and an additional seven contained cdt-V. All 14 cdt-positive
strains produced biologically active CDT, as demonstrated by a progressive
distension of cultured Chinese hamster ovary cells. The CDT-positive STEC
belonged to eight different serotypes, including sorbitol-fermenting O157 : NM
(non-motile). The data demonstrate that CDT is present in some STEC serotypes
only. However, more studies are required to evaluate whether CDT presence is
associated with severe disease.
PMID- 17030907
TI - Detection of enteroaggregative Escherichia coli in faecal samples from patients
in the community with diarrhoea.
AB - The aim of this study was to assess the usefulness of a multiplex PCR assay
targeting the aat, aaiA and astA genes for the detection of typical and atypical
enteroaggregative Escherichia coli (EAEC) in bacterial cultures from faecal
samples from patients with community-acquired diarrhoea. The isolates harbouring
these genes were also tested using the HEp-2 cell-adhesion assay to clarify their
EAEC status. aat, aai or astA was found in E. coli faecal isolates from 39 (7.8
%) of 500 patients, and 20 of these strains adhered to HEp-2 cells in a pattern
characteristic of EAEC. Eight isolates carrying the aai or astA gene but not the
aat gene were shown to be HEp-2 cell test positive, although 12 strains with this
genotype were HEp-2 cell test negative. Using the HEp-2 adhesion assay as the
gold standard, the addition of primers detecting aaiA and astA to the aat PCR
increased the number of EAEC isolates detected, but identified strains of E. coli
that were not EAEC. The variety of genotypes exhibiting aggregative adherence
highlights the problems associated with developing a molecular diagnostic test
for EAEC. This PCR assay detects a variety of strains exhibiting characteristics
of the EAEC group, making it a useful tool for identifying both typical and
atypical EAEC.
PMID- 17030908
TI - Antigenicity of borrelial protein BBK32 fragments in early Lyme borreliosis.
AB - Recombinantly produced borrelial BBK32 protein fragments originating from
Borrelia burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii were
evaluated as antigens in the serology of Lyme borreliosis (LB). In ELISA, a mid
portion hydrophilic fragment reacted with LB patient sera. Of the 23 patients
with culture- or PCR-positive erythema migrans (EM), 43 % at diagnosis and 52 %
at convalescence were positive for at least one Borrelia species-specific variant
BBK32 fragment antigen. In parallel ELISAs with BBK32 whole proteins from the
three borrelial subspecies as antigens, 17 % at diagnosis and 26 % at
convalescence were positive. These results suggest that BBK32 protein fragments
may improve the early IgG serology of LB compared to the BBK32 whole protein.
PMID- 17030909
TI - Rapid molecular identification of fungal pathogens in corneal samples from
suspected keratomycosis cases.
AB - An increase in the incidence of fungal infections has highlighted the need for
rapid and precise detection and identification methods in clinical mycology. This
report describes the data obtained on corneal samples from 24 patients with
suspected keratomycosis using a conventional cultural approach in parallel with
PCR amplification and sequencing of the internal transcribed spacers (ITSs) of
the rDNA regions. Using the cultural approach, seven samples (58.3 % of the 12
samples positive for an infectious pathogen) tested positive for a fungal
aetiology, with final identification taking a mean time of more than 5 days. In
two cases, diagnosis required 10 days. Using the ITS-based molecular approach, a
direct diagnosis was obtained in only five of the seven fungus-positive cases
(71.4 %) starting from the clinical samples, but identification was still
possible in all seven cases within 24 h (by using 16 h cultures for the two
remaining cases). Despite the less-than-optimal sensitivity when working directly
on clinical samples, the obtained data indicate that the molecular strategy used
in this study is a useful complement to the conventional diagnostic approaches
used for keratomycosis and, in particular, allows precise and fast fungal
identification, in response to the clinical requirements. Similar studies on
larger panels of patients and on different clinical samples are required for
further investigation of the clinical potential of ITS-based approaches in the
diagnosis of mycotic infections.
PMID- 17030910
TI - Rapid antibiotic sensitivity testing and trimethoprim-mediated filamentation of
clinical isolates of the Enterobacteriaceae assayed on a novel porous culture
support.
AB - A porous inorganic material (Anopore) was employed as a microbial culture and
microcolony imaging support. Rapid Anopore-based antibiotic sensitivity testing
(AST) methods were developed to assess the growth of clinical isolates, with the
primary focus on testing the response of the Enterobacteriaceae to trimethoprim,
but with the method supporting a wider applicability in terms of strains and
antibiotics. It was possible to detect the growth of Enterobacter aerogenes after
25 min culture and to distinguish a trimethoprim-sensitive from a trimethoprim
resistant strain with 40 min incubation. MIC(90) determinations were made on
Anopore; these were in good agreement with the results from the Vitek 2 and E
test methods. The Anopore method correctly identified sensitive (40/40) and
resistant (17/17) strains of the Enterobacteriaceae and other Gram-negative rods
within only 2-3 h culture. Additionally, a trimethoprim-resistant subpopulation
(10 % of population) could be detected by microcolony formation within 2 h, and a
smaller subpopulation (1 %) after 3.5 h. These results suggest that this is a
viable approach for the rapid AST of purified strains, and that it may be able to
deal with mixed populations. The microscopic examination of microcolonies during
AST is an advantage of this method which revealed additional information.
Filamentation triggered by trimethoprim was discovered in many species of the
Enterobacteriaceae for which this phenomenon has not previously been reported.
Filamentation was characterized by heterogeneity in terms of cell length, and
also uneven nucleic acid distribution and flattening of damaged cells. The
development and application of Anopore-based AST within clinical diagnostics is
discussed.
PMID- 17030911
TI - Insertion sequence ISEcp1-like element connected with a novel aph(2'') allele
[aph(2'')-Ie] conferring high-level gentamicin resistance and a novel
streptomycin adenylyltransferase gene in Enterococcus.
AB - Enterococcus casseliflavus HZ95 is an enterococcus with high-level resistance to
aminoglycosides. Nine genes responsible for high-level aminoglycoside resistance,
including aac(6')-Ie-aph(2'')-Ia, aph(2'')-Ib, aph(2'')-Ic, aph(2'')-Id, aph(3')
IIIa, aac(6')-Ii, ant(3')-Ia, ant(4')-Ia and ant(6')-Ia, were not detected in
HZ95. An 8 kb fragment from unconjugative plasmids of HZ95 was cloned, and
expressed gentamicin resistance in Escherichia coli DH5alpha. The genetic
structures ( approximately 8 kb DNA fragment) containing these aminoglycoside
modifying enzyme genes in Ent. casseliflavus HZ95 were determined. The deduced
amino acid sequence of the novel aph(2'') allele, aph(2'')-Ie, had 93.7 % amino
acid identity with APH(2'')-Id. The aph(2'')-Ie gene was bracketed upstream by an
insertion sequence (IS)Ecp1-like element and downstream by a streptomycin
adenylyltransferase gene (str). The streptomycin adenylyltransferase encoded by
the str gene had 80.3 % amino acid identity with the protein encoded by aadE. The
plasmid of approximately 16 kb could hybridize with a PCR-generated aph(2'')-Ie
intragenic probe. The ISEcp1-like element had 91 % identity with ISEcp1. ISEcp1,
which commonly acts as a key factor in the dissemination of CTX-M-type beta
lactamase genes in Gram-negative bacteria, has not been reported in Enterococcus.
PMID- 17030912
TI - Molecular characterization of isoniazid-resistant clinical isolates of
Mycobacterium tuberculosis from the USA.
AB - Drug-resistant tuberculosis poses a significant problem for treatment. The
mechanisms of resistance to the front-line drug isoniazid (INH) are complex and
can be mediated by katG, inhA and other unknown genes. To identify the percentage
of INH-resistant strains with no katG or inhA mutation, this study characterized
a panel of 28 clinical isolates of Mycobacterium tuberculosis and five mutants
derived from H37Rv resistant to INH. Seventeen of 33 resistant strains (51 %) had
katG mutations with 12 of the 17 strains having the most common KatG Ser315Thr
mutation. Three of the 17 strains with the KatG 315 mutation had an additional
mutation in the inhA promoter and were resistant to a high level of INH.
Seventeen of the 33 INH-resistant strains (51 %) had inhA mutations. The most
common inhA promoter mutation was -15C-->T and was present in 13 of the 17 inhA
mutations. This promoter mutation occurred alone without katG mutations and was
associated with a low level of INH and ethionamide resistance. However, other
inhA mutations were associated with katG mutations. No mutations were found in
the ndh gene. Three of 33 strains (9 %) had no mutations in katG, inhA or ndh,
indicating that their resistance was due to a new mechanism of resistance.
Detection of the KatG Ser315Thr mutation and the -15C-->T inhA mutation accounted
for 76 % (25/33) of the INH-resistant strains and should be useful for rapid
detection of INH-resistant strains by molecular tests.
PMID- 17030913
TI - High level of ciprofloxacin resistance and its molecular background among
Campylobacter jejuni strains isolated in the United Arab Emirates.
AB - The antibiotic sensitivity and the serotype and molecular type (MT) distribution
of 41 Campylobacter jejuni strains isolated from individual patients in Tawam
Hospital, Al Ain, United Arab Emirates, were investigated. While all strains were
sensitive to erythromycin (MIC 0.5-4 mg l(-1)), 35 isolates (85.4 %) exhibited
resistance to ciprofloxacin (MIC 8-64 mg l(-1)). All resistant strains carried
the Thr-86 to Ile mutation in the gyrase A (gyrA) gene, as shown by mismatch
amplification mutation assay (MAMA) and confirmed by sequencing. Based on the
partial sequences of gyrA, resistant isolates carried 10 distinct alleles, eight
of them representing new variants. Strains were assigned to 30 MTs based on the
combined results of PFGE and flaA PCR-RFLP typing. Eight of the 35 ciprofloxacin
resistant strains, isolated over a period of more than 1 year, represented the
largest MT, also carrying the same allelic variant of the gyrA gene. These
results show that the local incidence of fluoroquinolone resistance among C.
jejuni is one of the highest reported worldwide. It was also demonstrated that
stable MTs could persist for a relatively long time among the clonally unrelated
antibiotic-resistant isolates of C. jejuni. The data also emphasize the need to
replace fluoroquinolones as empirical therapy for diarrhoea of undiagnosed
aetiology.
PMID- 17030915
TI - An improved multiple-locus variable number of tandem repeats analysis for
Leptospira interrogans serovar Australis: a comparison with fluorescent amplified
fragment length polymorphism analysis and its use to redefine the molecular
epidemiology of this serovar in Queensland, Australia.
AB - In this study, an improved multiple-locus variable number of tandem repeats
analysis (MLVA) method based upon a previously published method is described.
Improvements to the method included redesigned primers and PCR conditions,
combined with pooled capillary electrophoresis using multicolored dyes. Allele
sizes were converted into an allele string, and each unique allele string was
assigned a numerical MLVA type (MVT). The improved MLVA method was then applied
to 96 previously characterized Leptospira interrogans serovar Australis isolates
from human and animal sources. The improved MLVA was found to have between six
and 13 alleles at each locus, compared with three to eight in the original. The
mean Hunter-Gaston diversity index (HGDI) for the improved MLVA method was 0.654,
compared with 0.599 in the original; this increase in diversity was largely due
to changes in the analysis of the variable number of tandem repeat (VNTR) data.
When the improved MLVA method was compared with the fluorescent amplified
fragment length polymorphism (FAFLP) method, there was a high level of
concordance between the profiles; however, the MLVA method produced an additional
four unique profiles amongst the subset of 30 isolates tested. Given that the
improved MLVA method was found to be superior to the original MLVA method, it was
subsequently used to redefine the molecular epidemiology of L. interrogans
serovar Australis in Queensland, Australia. Using cluster analysis, the authors
were able to demonstrate clonal links amongst rodent isolates, rodent and human
isolates, and rodent and canine isolates. These results highlight the role of
rodents in the disease, and also the potential role of MLVA in defining the
molecular epidemiology of L. interrogans.
PMID- 17030914
TI - Molecular typing and virulence markers of Yersinia enterocolitica strains from
human, animal and food origins isolated between 1968 and 2000 in Brazil.
AB - Molecular typing and virulence markers were used to evaluate the genetic profiles
and virulence potential of 106 Yersinia enterocolitica strains. Of these strains,
71 were bio-serotype 4/O : 3, isolated from human and animal clinical material,
and 35 were of biotype 1A or 2 and of diverse serotypes, isolated from food in
Brazil between 1968 and 2000. Drug resistance was also investigated. All the
strains were resistant to three or more drugs. The isolates showed a virulence
related phenotype in the aesculin, pyrazinamidase and salicin tests, except for
the food isolates, only two of which were positive for these tests. For the other
phenotypic virulence determinants (autoagglutination, Ca(++) dependence and Congo
red absorption), the strains showed a diverse behaviour. The inv, ail and ystA
genes were detected in all human and animal strains, while all the food isolates
were positive for inv, and 3 % of them positive for ail and ystA. The presence of
virF was variable in the three groups of strains. The strains were better
discriminated by PFGE than by enterobacterial repetitive intergenic consensus PCR
(ERIC-PCR). A higher genomic similarity was observed among the 4/O : 3 strains,
isolated from human and animal isolates, than among the food strains, with the
exception of two food strains possessing the virulence genes and grouped close to
the 4/O : 3 strains by ERIC-PCR. Unusually, the results revealed the virulence
potential of a bio-serotype 1A/O : 10 strain, suggesting that food contaminated
with Y. enterocolitica biotype 1A may cause infection. This also suggests that
ERIC-PCR may be used as a tool to reveal clues about the virulence potential of
Y. enterocolitica strains. Furthermore, the results also support the hypothesis
that animals may act as reservoirs of Y. enterocolitica for human infections in
Brazil, an epidemiological aspect that has not been investigated in this country,
confirming data from other parts of the world.
PMID- 17030916
TI - Isolation of Vibrio cholerae O1 strains similar to pre-seventh pandemic El Tor
strains during an outbreak of gastrointestinal disease in an island resort in
Fiji.
AB - Five strains of Vibrio cholerae O1, one each from an Australian and a New Zealand
tourist with gastrointestinal illness returning from an island resort in Fiji and
the remaining three from water sources located in the same resort, were
extensively characterized. Conventional phenotypic traits that are used for
biotyping of O1 V. cholerae categorized all five strains as belonging to the El
Tor biotype. Genetic screening of 11 regions that are associated with virulence
in V. cholerae showed variable results. The absence of genes comprising Vibrio
seventh pandemic island-I (VSP-I) and VSP-II in all the strains indicated that
these strains were very similar to the pre-seventh pandemic V. cholerae O1 El Tor
strains. The ctxAB genes were absent in all strains whereas orfU and zot were
present in four strains, indicating that the strains were non-toxigenic. Four
strains carried a truncated CTX prophage. Although epidemiological and molecular
studies suggested that these strains did not cause cholera amongst tourists at
the resort, their similarity to pre-seventh pandemic strains, their prior
association with gastrointestinal illness and their presence in the island resort
setting warrant more attention.
PMID- 17030917
TI - Genetic characteristics of Matlab variants of Vibrio cholerae O1 that are hybrids
between classical and El Tor biotypes.
AB - The Matlab variants of Vibrio cholerae O1, defined as hybrids between the
classical and El Tor biotypes, were first isolated from hospitalized patients
with acute secretory diarrhoea in Matlab, a rural area of Bangladesh. These
variants could not be categorized as classical or El Tor biotypes by phenotypic
and genotypic tests, and had representative traits of both the biotypes. A number
of virulence-associated genes and/or gene clusters were screened by PCR and DNA
sequencing. El Tor-specific gene clusters, Vibrio seventh-pandemic islands (VSP)
I and -II and repeat toxin (RTX) were present in the genome of these variants,
indicating their El Tor lineage, whereas the nucleotide-sequence-derived CtxB
amino acid sequence of these strains grouped them under the classical biotype.
Matlab variants possessed all the necessary genes to initiate pandemics. The
genetic relatedness of Matlab variants to the V. cholerae strains recently
isolated in Mozambique is another important observation of this study, which
underscores the epidemiological significance of Matlab variants.
PMID- 17030918
TI - An outbreak of psittacosis due to Chlamydophila psittaci genotype A in a
veterinary teaching hospital.
AB - An outbreak of psittacosis in a veterinary teaching hospital was recognized in
December 2004. Outbreak management was instituted to evaluate the extent of the
outbreak and to determine the avian source. Real-time PCR, serologic testing and
sequencing of the ompA gene of Chlamydophila psittaci were performed. Sputum
samples from patients, throat-swab samples from exposed students and staff, and
faecal specimens from parrots and pigeons were tested. In this outbreak, 34 %
(10/29) of the tested individuals were infected. The clinical features of the
infection ranged from none to sepsis with multi-organ failure requiring intensive
care-unit admission. C. psittaci genotype A was identified as the outbreak
strain. Parrots, recently exposed to a group of cockatiels coming from outside
the teaching facility, which were used in a practical class, appeared to be the
source of the outbreak. One of the tested pigeons harboured an unrelated C.
psittaci genotype B strain. The microbiological diagnosis by real-time PCR on
clinical specimens allowed for rapid outbreak management; subsequent genotyping
of the isolates identified the avian source. Recommendations are made to reduce
the incidence and extent of future outbreaks.
PMID- 17030919
TI - Arthroconidia production in Trichophyton rubrum and a new ex vivo model of
onychomycosis.
AB - The dermatophyte fungus Trichophyton rubrum often produces arthroconidia in vivo,
and these cells are thought to be involved in pathogenesis, and, in shed skin
scales, to act as a source of infection. The purpose of this study was (i) to
examine the environmental and iatrogenic factors which affect arthroconidiation
in T. rubrum in vitro, (ii) to look at arthroconidia formation in a large number
of clinical isolates of T. rubrum and (iii) to develop a new model for the study
of arthroconidia formation in nail tissue. Arthroconidia production was studied
in T. rubrum grown on a number of media and under conditions of varying pH,
temperature and CO(2) concentration. The effect of the presence of antifungals
and steroids on arthroconidia formation was also examined. Nail powder from the
healthy toenails of volunteers was used as a substrate for arthroconidial
production. On Sabouraud dextrose agar in the presence of 10 % CO(2) plus air,
arthroconidial formation occurred optimally at 37 degrees C and pH 7.5, and was
maximal at 10 days. Most isolates of T. rubrum showed a similar level of
arthroconidial production, and only two out of 50 strains were unable to produce
arthroconidia. Subinhibitory levels of some antifungals and betamethasone
resulted in the stimulation of arthroconidia formation. Arthroconidial production
in ground nail material also occurred under the same optimal conditions, but took
longer to reach maximal levels (14 days). These in vitro and ex vivo results
provide a useful basis for the understanding of arthroconidium formation in vivo
in infected tissues such as nails.
PMID- 17030920
TI - Canine dermatophytosis caused by an anthropophilic species: molecular and
phenotypical characterization of Trichophyton tonsurans.
AB - Microsporum canis is the most common species isolated from canine and feline
dermatophytosis in the world. However, this study reports a rare case of canine
dermatophytosis caused by the anthropophilic dermatophyte Trichophyton tonsurans
in the city of Fortaleza, Ceara, Brazil. The fungal characterization was
performed by classical mycological examination and by genotypical analysis using
the restriction enzymes Sau3A, RsaI, DdeI and EcoRI. The phenotypical
characteristics were compatible with T. tonsurans. The results obtained in the
genotypical analysis were similar to the digestion pattern of the ITS sequences
for T. tonsurans strains. In addition, an antifungal susceptibility test was
performed with griseofulvin, ketoconazole and itraconazole. The MICs were 0.5
microg ml(-1) for griseofulvin, 0.25 microg ml(-1) for ketoconazole and 1 microg
ml(-1) for itraconazole. This study emphasizes the adaptability of anthropophilic
fungi such as T. tonsurans to animal conditions.
PMID- 17030921
TI - Intractable colitis associated with chronic granulomatous disease.
AB - The case of a 20-year-old Japanese man, diagnosed as having autosomal recessive
chronic granulomatous disease (CGD), who was being treated with corticosteroids
for intractable unclassified colitis, is described. He died from multiple organ
failure following disseminated intravascular coagulation secondary to
disseminated varicella-zoster virus (VZV) infection. He was diagnosed as an index
case of CGD when 2 years old, was inoculated against VZV at the age of 5 years
and had had an unremarkable course for 19 years. He was admitted to hospital
because of a third episode of recurrent bloody diarrhoea. Clinical remission for
each episode was achieved by intravenous corticosteroid therapy. Unclassified
colitis associated with CGD was diagnosed based on a colonic biopsy demonstrating
characteristic macrophages with lipofuscin deposits. From a treatment viewpoint,
idiopathic inflammatory bowel disease (IBD) should be differentiated from
secondary IBD occurring in CGD, in which immunosuppressive drugs including
corticosteroids, still the mainstay of IBD treatment, should be avoided.
PMID- 17030922
TI - Enterohepatic Helicobacter species isolated from the ileum, liver and colon of a
baboon with pancreatic islet amyloidosis.
AB - Microaerobic bacteria were isolated from a baboon with pancreatic islet
amyloidosis and hepatitis. Phenotypic and molecular analyses identified two
distinct helicobacters. Analyses of 16S rRNA demonstrated "Helicobacter macacae"
in the ileum and liver, and Helicobacter cinaedi in the colon. To the best of the
authors' knowledge, this is the first report describing the isolation of
enterohepatic Helicobacter species from a baboon.
PMID- 17030923
TI - Central nervous system borreliosis mimicking a pontine tumour.
AB - In childhood, facial nerve palsy and headache are typical symptoms of second and
third stage neuroborreliosis. While focal demyelination is occasionally observed
on MRI scans, the appearance of a tumorous lesion is extremely rare. The case of
a 10-year-old girl with neuroborreliosis mimicking a space-occupying lesion in
the brainstem, without any previously recognized manifestations of borreliosis,
is reported.
PMID- 17030924
TI - Molecular evidence for vertical transmission of listeriosis, Taiwan.
AB - The case is presented of a pregnant woman at the 31st week of gestation with
Listeria monocytogenes bacteraemia and microabscess formation in the endometrium,
who delivered an infant with disseminated infection (meningitis and bacteraemia).
The two patients were successfully treated with intravenous ampicillin and
gentamicin. Molecular typing using random amplified polymorphic DNA (RAPD)
analysis disclosed that three isolates from the mother (blood) and infant (blood
and cerebrospinal fluid) had identical RAPD profiles.
PMID- 17030925
TI - Aeromonas agar is a useful selective medium for isolating aeromonads from faecal
samples.
PMID- 17030926
TI - A CTX-M extended-spectrum beta-lactamase in Pseudomonas aeruginosa and
Stenotrophomonas maltophilia.
PMID- 17030927
TI - A CARB-like beta-lactamase gene from a multiple-drug-resistant Pseudomonas
aeruginosa clinical isolate in China.
PMID- 17030928
TI - Enterobacteria producing extended-spectrum beta-lactamases and IMP-1 metallo-beta
lactamases isolated from Brazilian hospitals.
PMID- 17030929
TI - International panel says CIHR needs management overhaul.
PMID- 17030930
TI - Ibuprofen redux.
PMID- 17030931
TI - Injection site gets 16-month extension.
PMID- 17030932
TI - Schwarzenegger vetoes single-payer bill.
PMID- 17030933
TI - Hepatitis E and cholera outbreak in Kathmandu.
PMID- 17030934
TI - Quebec specialist taking government to court.
PMID- 17030935
TI - Plan B available to women 18 and older in US.
PMID- 17030936
TI - Uncontrollable movements in patient with diabetes mellitus.
PMID- 17030937
TI - Patient sheet: tips for avoiding problems with polypharmacy.
PMID- 17030938
TI - An infant with the "setting-sun" eye phenomenon.
PMID- 17030939
TI - Accountability sought by patients following adverse events from medical care: the
New Zealand experience.
AB - BACKGROUND: Unlike Canada's medical malpractice system, patients in New Zealand
who are dissatisfied with the quality of their care may choose between 2 well
established medicolegal paths: one leads to monetary compensation and the other
to nonmonetary forms of accountability. We compared the forms of accountability
sought by patients and families in New Zealand who took different types of legal
action following a medical injury. This study offers insights into the forms of
accountability sought by injured patients and may help to inform tort-reform
initiatives. METHODS: We reviewed compensation claims submitted to the Accident
Compensation Corporation (ACC), New Zealand's national no-fault insurer,
following injuries associated with admission to a public hospital in 1998 (n =
582). We also reviewed complaint letters (n = 254) submitted to the national
Health and Disability Commissioner (HDC) that same year to determine the forms of
accountability sought by injured patients. We used univariable and multivariable
analyses to compare sociodemographic and socioeconomic characteristics of
patients who sought nonmonetary forms of accountability with those of patients
who claimed compensation. RESULTS: Of 154 injured patients whose complaints were
sufficiently detailed to allow coding, 50% sought corrective action to prevent
similar harm to future patients (45% system change, 6% review of involved
clinician's competence) and 40% wanted more satisfying communication (34%
explanation, 10% apology). The odds that patients would seek compensation were
significantly increased if they were in their prime working years (aged between
30 and 64 years) (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.14-2.41)
or had a permanent disability as a result of their injury (OR 1.75, 95% CI 1.14
2.70). When injuries resulted in death, the odds of a compensation claim to the
ACC were about one-eighth those of a complaint to the HDC (OR 0.13, 95% CI 0.08
0.23). INTERPRETATION: Injured patients who pursue medicolegal action seek
various forms of accountability. Compensation is important to some, especially
when economic losses are substantial (e.g., with injury during prime working
years or severe nonfatal injuries). However, others have purely nonmonetary
goals, and ensuring alternative options for redress would be an efficient and
effective response to their needs.
PMID- 17030940
TI - Monetary and nonmonetary accountability following adverse medical events: options
for Canadian patients.
PMID- 17030941
TI - Is the Canadian health care system ready for donation after cardiac death? A note
of caution.
PMID- 17030942
TI - Clinical applications of cardiovascular magnetic resonance imaging.
AB - Cardiovascular magnetic resonance imaging (MRI) has evolved from an effective
research tool into a clinically proven, safe and comprehensive imaging modality.
It provides anatomic and functional information in acquired and congenital heart
disease and is the most precise technique for quantification of ventricular
volumes, function and mass. Owing to its excellent interstudy reproducibility,
cardiovascular MRI is the optimal method for assessment of changes in ventricular
parameters after therapeutic intervention. Delayed contrast enhancement is an
accurate and robust method used in the diagnosis of ischemic and nonischemic
cardiomyopathies and less common diseases, such as cardiac sarcoidosis and
myocarditis. First-pass magnetic contrast myocardial perfusion is becoming an
alternative to radionuclide techniques for the detection of coronary
atherosclerotic disease. In this review we outline the techniques used in
cardiovascular MRI and discuss the most common clinical applications.
PMID- 17030943
TI - Promotion of traditional lifestyles.
PMID- 17030944
TI - Clinical utility of the Coombs test.
PMID- 17030945
TI - Changing ethics: where to start?
PMID- 17030947
TI - Integrin signaling is critical for pathological angiogenesis.
AB - The process of postnatal angiogenesis plays a crucial role in pathogenesis of
numerous diseases, including but not limited to tumor growth/metastasis, diabetic
retinopathy, and in tissue remodeling upon injury. However, the molecular events
underlying this complex process are not well understood and numerous issues
remain controversial, including the regulatory function of integrin receptors. To
analyze the role of integrin phosphorylation and signaling in angiogenesis, we
generated knock-in mice that express a mutant beta3 integrin unable to undergo
tyrosine phosphorylation. Two distinct models of pathological angiogenesis
revealed that neovascularization is impaired in mutant beta3 knock-in mice. In an
ex vivo angiogenesis assay, mutant beta3 knock-in endothelial cells did not form
complete capillaries in response to vascular endothelial growth factor (VEGF)
stimulation. At the cellular level, defective tyrosine phosphorylation in mutant
beta3 knock-in cells resulted in impaired adhesion, spreading, and migration of
endothelial cells. At the molecular level, VEGF stimulated complex formation
between VEGF receptor-2 and beta3 integrin in wild-type but not in mutant beta3
knock-in endothelial cells. Moreover, phosphorylation of VEGF receptor-2 was
significantly reduced in cells expressing mutant beta3 compared to wild type,
leading to impaired integrin activation in these cells. These findings provide
novel mechanistic insights into the role of integrin-VEGF axis in pathological
angiogenesis.
PMID- 17030948
TI - IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent
colitis.
AB - Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the
gastrointestinal tract that is caused in part by a dysregulated immune response
to the intestinal flora. The common interleukin (IL)-12/IL-23p40 subunit is
thought to be critical for the pathogenesis of IBD. We have analyzed the role of
IL-12 versus IL-23 in two models of Helicobacter hepaticus-triggered T cell
dependent colitis, one involving anti-IL-10R monoclonal antibody treatment of
infected T cell-sufficient hosts, and the other involving CD4+ T cell transfer
into infected Rag-/- recipients. Our data demonstrate that IL-23 and not IL-12 is
essential for the development of maximal intestinal disease. Although IL-23 has
been implicated in the differentiation of IL-17-producing CD4+ T cells that alone
are sufficient to induce autoimmune tissue reactivity, our results instead
support a model in which IL-23 drives both interferon gamma and IL-17 responses
that together synergize to trigger severe intestinal inflammation.
PMID- 17030949
TI - Interleukin-23 drives innate and T cell-mediated intestinal inflammation.
AB - Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the
gastrointestinal tract involving aberrant activation of innate and adaptive
immune responses. We have used two complementary models of IBD to examine the
roles of interleukin (IL)-12 family cytokines in bacterially induced intestinal
inflammation. Our results clearly show that IL-23, but not IL-12, is essential
for the induction of chronic intestinal inflammation mediated by innate or
adaptive immune mechanisms. Depletion of IL-23 was associated with decreased
proinflammatory responses in the intestine but had little impact on systemic T
cell inflammatory responses. These results newly identify IL-23 as a driver of
innate immune pathology in the intestine and suggest that selective targeting of
IL-23 represents an attractive therapeutic approach in human IBD.
PMID- 17030950
TI - High affinity germinal center B cells are actively selected into the plasma cell
compartment.
AB - A hallmark of T cell-dependent immune responses is the progressive increase in
the ability of serum antibodies to bind antigen and provide immune protection.
Affinity maturation of the antibody response is thought to be connected with the
preferential survival of germinal centre (GC) B cells that have acquired
increased affinity for antigen via somatic hypermutation of their immunoglobulin
genes. However, the mechanisms that drive affinity maturation remain obscure
because of the difficulty in tracking the affinity-based selection of GC B cells
and their differentiation into plasma cells. We describe a powerful new model
that allows these processes to be followed as they occur in vivo. In contrast to
evidence from in vitro systems, responding GC B cells do not undergo plasma cell
differentiation stochastically. Rather, only GC B cells that have acquired high
affinity for the immunizing antigen form plasma cells. Affinity maturation is
therefore driven by a tightly controlled mechanism that ensures only antibodies
with the greatest possibility of neutralizing foreign antigen are produced.
Because the body can sustain only limited numbers of plasma cells, this "quality
control" over plasma cell differentiation is likely critical for establishing
effective humoral immunity.
PMID- 17030952
TI - Full of sound and fury, but signifying something: XVI International AIDS
Conference, Toronto, Canada, August 13-18, 2006.
AB - The biennial AIDS conference is often exhausting and irritating, but it offers a
unique view of how science and society interact. It still deserves the support of
basic scientists.
PMID- 17030951
TI - Resolution of a chronic viral infection after interleukin-10 receptor blockade.
AB - A defining characteristic of persistent viral infections is the loss and
functional inactivation of antiviral effector T cells, which prevents viral
clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by
modulating the function of T cells and antigen-presenting cells. In this paper,
we report that IL-10 production is drastically increased in mice persistently
infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10
receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of
the persistent infection. IL-10 secretion was diminished and interferon gamma
production by antiviral CD8+ T cells was enhanced. In persistently infected mice,
CD8alpha+ dendritic cell (DC) numbers declined early after infection, whereas
CD8alpha- DC numbers were not affected. CD8alpha- DCs supported IL-10 production
and subsequent dampening of antiviral T cell responses. Therapeutic IL-10R
blockade broke the cycle of IL-10-mediated immune suppression, preventing IL-10
priming by CD8alpha- DCs and enhancing antiviral responses and thereby resolving
infection without causing immunopathology.
PMID- 17030953
TI - Mass spectrometric detection of tissue proteins in plasma.
AB - It has long been thought that blood plasma could serve as a window into the state
of one's organs in health and disease because tissue-derived proteins represent a
significant fraction of the plasma proteome. Although substantial technical
progress has been made toward the goal of comprehensively analyzing the blood
plasma proteome, the basic assumption that proteins derived from a variety of
tissues could indeed be detectable in plasma using current proteomics
technologies has not been rigorously tested. Here we provide evidence that such
tissue-derived proteins are both present and detectable in plasma via direct mass
spectrometric analysis of captured glycopeptides and thus provide a conceptual
basis for plasma protein biomarker discovery and analysis.
PMID- 17030955
TI - Thermoregulatory feeding in newborn infants: an update.
PMID- 17030954
TI - EMB-4: a predicted ATPase that facilitates lin-12 activity in Caenorhabditis
elegans.
AB - The sel-6 gene was previously identified in a screen for suppressors of the egg
laying defect associated with hypermorphic alleles of lin-12 (Tax et al. 1997).
Here we show that sel-6 and two other previously defined genes, mal-2 and emb-4,
are the same gene, now called "emb-4." We perform a genetic and molecular
characterization of emb-4 and show that it functions cell autonomously as a
positive regulator of lin-12 activity. Viable alleles identified as suppressors
of lin-12 are partial loss-of-function mutations, whereas the null phenotype
encompasses a range of lethal terminal phenotypes that apparently are not related
to loss of lin-12/Notch signaling. emb-4 encodes a large nuclearly localized
protein containing a predicted ATPase domain and has apparent orthologs in
fission yeast, plants, and animals.
PMID- 17030956
TI - Point: uncertainty in the economic analysis of school-based obesity prevention
programs: urgent need for quality evaluation.
PMID- 17030957
TI - Counterpoint: uncertainty in the economic analysis of school-based obesity
prevention programs: urgent need for quality evaluation.
PMID- 17030958
TI - Obesity in older adults: a systematic review of the evidence for diagnosis and
treatment.
AB - OBJECTIVE: Although obesity is increasing in older U.S. adults, treatment is
controversial in this age group. We sought to examine evidence concerning
obesity's health-related risks, diagnostic methods, and treatment outcomes in
older individuals. RESEARCH METHODS AND PROCEDURES: We searched MEDLINE and
Cochrane Library databases, consulted with experts, and examined bibliographies
for English language studies discussing obesity in older adults (mean age > or =
60), published between January 1980 and November 2005. Inclusion criteria were
met by 32 longitudinal analyses, seven diagnostic studies, and 17 randomized
controlled trial articles. At least two authors independently reviewed and
abstracted study design, population, results, and quality information. RESULTS:
Correlations between body fat and three anthropometric measures (BMI, waist
circumference, waist-to-hip ratio) decrease with age but remain clinically
significant. Obesity contributes to risk for several cardiovascular endpoints,
some cancers, and impaired mobility but protects against hip fracture. The
association between obesity and mortality declines as age increases. Intensive
counseling strategies incorporating behavioral, dietary, and exercise components
promote a weight loss of 3 to 4 kg over 1 to 3.3 years. The loss is linked with
improved glucose tolerance, improved physical functioning, reduced incidence of
diabetes and a combined hypertension and cardiovascular endpoint, and reduced
bone density. DISCUSSION: In older adults, obesity can be diagnosed with standard
clinical measures. Intensive counseling can promote modest sustained weight loss,
but data are insufficient to evaluate surgical or pharmacological options.
Obesity treatment is most likely to benefit individuals with high cardiovascular
risk. Limited data suggest possible functional improvement. Treatment should
incorporate measures to avoid bone loss.
PMID- 17030959
TI - The promoter region of the adiponectin gene is a determinant in modulating
insulin sensitivity in childhood obesity.
AB - We investigated the association of the -11,391G>A, -11,377G>C, +45T>G, and
+276G>T adiponectin single-nucleotide polymorphisms (SNPs) and expected
haplotypes with the insulin resistance (IR) state in overweight/obese children;
by using the haplotype background analysis, we also assessed the effect of each
SNP independently. GG genotype at the -11,391 locus was associated with higher
fasting insulin levels and homeostasis model assessment-IR index and lower
adiponectin levels compared with GA + AA genotypes (p = 0.01, 0.002, and 0.03,
respectively). Those heterozygous and homozygous for G allele at the -11,377
locus showed higher fasting glucose (p = 0.001 for both), fasting insulin (p =
0.001 for both), homeostasis model assessment-IR index (p < 0.001 for both), and
triglyceride levels (p = 0.02 and 0.03, respectively) and lower adiponectin
levels (p = 0.002 and 0.02, respectively) compared with C homozygotes. The +45G
carriers showed higher fasting and 2-hour glucose levels (p = 0.01 for both) and
lower adiponectin levels (p = 0.02) compared with non-carriers. Haplotype
analysis suggested that, considering the same haplotypic background, each of the
three polymorphisms exerted an independent effect on investigated parameters. The
-11,391G>A, -11,377C>G, and +45T>G SNPs are associated with IR syndrome in
overweight/obese children; they independently influence the investigated
variables. The effect of +45T>G SNP seems to be marginal compared with the
promoter SNPs. The GGT haplotype is associated with the highest degree of IR.
PMID- 17030960
TI - Adiponectin and membrane fluidity of erythrocytes in normotensive and
hypertensive men.
AB - OBJECTIVE: Abnormalities in physicochemical properties of the cell membranes may
underlie the defects that are strongly linked to hypertension. Recent evidence
indicates that adiponectin may have protective effects against cardiovascular
diseases. The purpose of the present study was to assess the possible link
between plasma adiponectin and membrane fluidity in normotensive (NT) and
hypertensive (HT) men. RESEARCH METHODS AND PROCEDURES: We measured the membrane
fluidity (a reciprocal value of membrane microviscosity) of erythrocytes in NT
and HT men by using an electron paramagnetic resonance and spin-labeling method.
RESULTS: The order parameter (S) for the spin label agent (5-nitroxide stearate)
and the peak height ratio (h0/h(-1)) for 16-nitroxide stearate in the electron
paramagnetic resonance spectra of erythrocytes were significantly higher in HT
men than in NT men, indicating that membrane fluidity of erythrocytes was
decreased in HT men compared with NT men. Both of plasma adiponectin and nitric
oxide (NO) metabolite levels were significantly lower in HT men than in NT men.
The plasma adiponectin levels were correlated with plasma NO metabolites. The S
and the h0/h(-1) of erythrocytes were inversely correlated with the plasma
adiponectin and NO metabolite levels, indicating that the decreased membrane
fluidity of erythrocytes was associated with hypoadiponectinemia and reduced
plasma NO metabolites. DISCUSSION: The results of the present study demonstrated
that plasma adiponectin levels were lower in HT men than in NT men and that
hypoadiponectinemia was associated with decreased membrane fluidity of
erythrocytes. The finding suggests that adiponectin may be linked to the
rheologic behavior of the erythrocytes and the microcirculation in men, at least
in part, by the NO-dependent mechanism.
PMID- 17030961
TI - High-molecular weight adiponectin isoforms increase after biliopancreatic
diversion in obese subjects.
AB - OBJECTIVE: Our objective was to test the effect of biliopancreatic diversion
(BDP) in adiponectin multimerization. Adiponectin, the major protein secreted by
adipose tissue, circulates in plasma in different isoforms. The most clinically
relevant oligomers are high-molecular weight (HMW) multimers and low-molecular
weight (LMW) trimers. Contrasting data on the effect of weight loss on
adiponectin isoforms have been reported. RESEARCH METHODS AND PROCEDURES: We
measured total plasma adiponectin and HMW and LMW adiponectin oligomers (by
Western blot analysis) before and 1 month after BPD, in 18 severely obese
subjects. RESULTS: One month after BPD, body weight decreased approximately 11%.
Total adiponectin showed significant increase after BPD. In addition, we found a
significant increase in HMW (percentage) adiponectin oligomers. We found a
significant inverse correlation between HMW (percentage) and BMI before and after
BPD. Homeostasis model of assessment-insulin resistance decreased significantly
after the BPD, without any significant correlation with total serum adiponectin
and adiponectin oligomers. DISCUSSION: A moderate weight loss after BPD increases
total and HMW adiponectin oligomers. The significant correlation between BMI and
HMW (percentage) adiponectin oligomers but not between BMI and total adiponectin
might indicate a role of body fat mass in regulation of adiponectin
multimerization. These data suggest that HMW oligomers represent a very sensitive
parameter to short-term BMI changes after BPD.
PMID- 17030962
TI - 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue and prospective
changes in body weight and insulin resistance.
AB - OBJECTIVE: Increased mRNA and activity levels of 11beta-hydroxysteroid
dehydrogenase type 1 (11betaHSD1) in human adipose tissue (AT) are associated
with obesity and insulin resistance. The aim of our study was to investigate
whether 11betaHSD1 expression or activity in abdominal subcutaneous AT of non
diabetic subjects are associated with subsequent changes in body weight and
insulin resistance [homeostasis model assessment of insulin resistance (HOMA
IR)]. RESEARCH METHODS AND PROCEDURES: Prospective analyses were performed in 20
subjects (two whites and 18 Pima Indians) who had baseline measurements of
11betaHSD1 mRNA and activity in whole AT (follow-up, 0.3 to 4.9 years) and in 47
Pima Indians who had baseline assessments of 11betaHSD1 mRNA in isolated
adipocytes (follow-up, 0.8 to 5.3 years). RESULTS: In whole AT, although
11betaHSD1 mRNA levels showed positive associations with changes in weight and
HOMA-IR, 11betaHSD1 activity was associated with changes in HOMA-IR but not in
body weight. 11betaHSD1 mRNA levels in isolated adipocytes were not associated
with follow-up changes in any of the anthropometric or metabolic variables.
DISCUSSION: Our results indicate that increased expression of 11betaHSD1 in
subcutaneous abdominal AT may contribute to risk of worsening obesity and insulin
resistance. This prospective relationship does not seem to be mediated by
increased 11betaHSD1 expression in adipocytes.
PMID- 17030963
TI - Effects of resistant starch, a non-digestible fermentable fiber, on reducing body
fat.
AB - OBJECTIVE: To assess the effects of energy dilution with non-fermentable and
fermentable fibers on abdominal fat and gut peptide YY (PYY) and glucagon-like
peptide (GLP)-1 expressions, three rat studies were conducted to: determine the
effects of energy dilution with a non-fermentable fiber, compare similar fiber
levels of fermentable and non-fermentable fibers, and compare similar
metabolizable energy dilutions with fermentable and non-fermentable fibers.
RESEARCH METHODS AND PROCEDURES: In Study 1, rats were fed one of three diets
with different metabolizable energy densities. In Study 2, rats were fed diets
with similar fiber levels using high amylose-resistant cornstarch (RS) or
methylcellulose. In Study 3, rats were fed diets with a similar dilution of
metabolizable energy using cellulose or RS. Measurements included food intake,
body weight, abdominal fat, plasma PYY and GLP-1, gastrointestinal tract weights,
and gene transcription of PYY and proglucagon. RESULTS: Energy dilution resulted
in decreased abdominal fat in all studies. In Study 2, rats fed fermentable RS
had increased cecal weights and plasma PYY and GLP-1, and increased gene
transcription of PYY and proglucagon. In Study 3, RS-fed rats had increased short
chain fatty acids in cecal contents, plasma PYY (GLP-1 not measured), and gene
transcription for PYY and proglucagon. DISCUSSION: Inclusion of RS in the diet
may affect energy balance through its effect as a fiber or a stimulator of PYY
and GLP-1 expression. Increasing gut hormone signaling with a bioactive
functional food such as RS may be an effective natural approach to the treatment
of obesity.
PMID- 17030964
TI - Thermoregulatory control of feeding and sleep in premature infants.
AB - OBJECTIVE: The aim of the present study was to test the thermoregulatory feeding
control hypothesis in sleeping, premature infants. RESEARCH METHODS AND
PROCEDURES: In premature infants, the energy supply from food intake is crucial
for (in order of importance): organ operation, body homeothermia, and optimal
growth. The Himms-Hagen model of thermoregulatory feeding control involving
activation of heat production by brown adipose tissue (BAT) was formulated on the
basis of work in (awake) rats. This hypothesis has also been put forward for the
human neonate, which can also use BAT to produce metabolic heat. According to the
model, feeding episodes occur during a transient increase in body temperature.
Feeding is initiated by a dip in blood glucose concentration after sugar uptake
by activated BAT. RESULTS: In 14 neonates (bottle-fed on demand), food intake
always took place during an increase in skin temperature (+0.19 +/- 0.21 degrees
C). Awakening occurred 18 +/- 17 minutes after the minimum skin temperature level
had been reached. When feeding time was imposed, feeding was not necessarily
situated during an increase in skin temperature, and the sleep duration after
food intake increased significantly (+43%). This could be considered as an
adaptive response to the short-term sleep deprivation and/or stress elicited by
an imposed feeding rhythm. DISCUSSION: The validity of the model supports the use
of on-demand feeding in neonatal care units, in accordance with the infant's
physiological body temperature oscillations.
PMID- 17030966
TI - Differential effects of gastric bypass and banding on circulating gut hormone and
leptin levels.
AB - OBJECTIVE: To quantify plasma concentrations of hormones that regulate energy
homeostasis in order to establish possible mechanisms for greater weight loss
after Roux-en-Y gastric bypass (RYGBP) compared with gastric banding (BND).
RESEARCH METHODS AND PROCEDURES: Four groups of women were studied: lean (n = 8;
mean BMI, 21.6 kg/m2); BND (n = 9; BMI, 35.8; 25% weight loss), RYGBP (n = 9;
BMI, 34.2; 36% weight loss), and controls matched for BMI to the surgical groups
(n = 11; BMI, 34.4). RESULTS: Fasting total peptide YY (PYY) and PYY(3-36)
immunoreactivity were similar among all groups, but the postprandial response in
the RYGBP group was exaggerated, such that 30 minutes after the meal, total and
PYY(3-36) levels were 2- to 4-fold greater compared with all other groups.
Maximal postprandial suppression of total ghrelin was blunted in the BND group
(13%) compared with RYGBP (27%). Postprandial suppression of octanoylated ghrelin
was also less in BND (29%) compared with RYGBP (56%). Fasting insulin was lower
in RYGBP (6.6 microU/mL) compared with BND (10.0 microU/mL). Compared with lean
controls, leptin concentrations were significantly higher in BND but not in
RYGBP. There was a greater increase in post-meal satiety in the RYGBP group
compared with BND and overweight controls. DISCUSSION: The differences between
RYGBP and BND subjects in postprandial concentrations of PYY and ghrelin would be
expected to promote increased satiety and earlier meal termination in RYGBP and
may aid in greater weight loss. The differences in insulin and leptin
concentrations associated with these procedures may also reflect differences in
insulin sensitivity and energy partitioning.
PMID- 17030967
TI - Physiological evidence for the involvement of peptide YY in the regulation of
energy homeostasis in humans.
AB - OBJECTIVE: To explore the potential role of the endogenous peptide YY (PYY) in
the long-term regulation of body weight and energy homeostasis. RESEARCH METHODS
AND PROCEDURES: Fasting and postprandial plasma PYY concentrations were measured
after an overnight fast and 30 to 180 minutes after a standardized meal in 29 (21
men/8 women) non-diabetic subjects, 16 of whom had a follow-up visit 10.8 +/- 1.4
months later. Ratings of hunger and satiety were collected using visual analog
scales. Resting metabolic rate (RMR) (15-hour RMR) and respiratory quotient (RQ)
were assessed using a respiratory chamber. RESULTS: Fasting PYY concentrations
were negatively correlated with various markers of adiposity and negatively
associated with 15-hour RMR (r = -0.46, p = 0.01). Postprandial changes in PYY
(area under the curve) were positively associated with postprandial changes in
ratings of satiety (r = 0.47, p = 0.01). The maximal PYY concentrations achieved
after the meal (peak PYY) were negatively associated with 24-hour RQ (r = -0.41,
p = 0.03). Prospectively, the peak PYY concentrations were negatively associated
with changes in body weight (r = -0.58, p = 0.01). DISCUSSION: Our data indicate
that the endogenous PYY may be involved in the long-term regulation of body
weight. It seems that this long-term effect was not exclusively driven by the
modulation of food intake but also by the control of energy expenditure and lipid
metabolism.
PMID- 17030965
TI - Decreased expression of adipogenic genes in obese subjects with type 2 diabetes.
AB - OBJECTIVE: Our objective was to delineate the potential role of adipogenesis in
insulin resistance and type 2 diabetes. Obesity is characterized by an increase
in adipose tissue mass resulting from enlargement of existing fat cells
(hypertrophy) and/or from increased number of adipocytes (hyperplasia). The
inability of the adipose tissue to recruit new fat cells may cause ectopic fat
deposition and insulin resistance. RESEARCH METHODS AND PROCEDURES: We examined
the expression of candidate genes involved in adipocyte proliferation and/or
differentiation [CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPdelta, GATA
domain-binding protein 3 (GATA3), C/EBPbeta, peroxisome proliferator-activated
receptor (PPAR) gamma2, signal transducer and activator of transcription 5A
(STAT5A), Wnt-10b, tumor necrosis factor alpha, sterol regulatory element-binding
protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin
related protein (PGAR), insulin-like growth factor 1, PPARgamma coactivator
1alpha, PPARgamma coactivator 1beta, and PPARdelta] in subcutaneous adipose
tissue from 42 obese individuals with type 2 diabetes and 25 non-diabetic
subjects matched for age and obesity. RESULTS: Insulin sensitivity was measured
by a 3-hour 80 mU/m2 per minute hyperinsulinemic glucose clamp (100 mg/dL). As
expected, subjects with type 2 diabetes had lower glucose disposal (4.9 +/- 1.9
vs. 7.5 +/- 2.8 mg/min per kilogram fat-free mass; p < 0.001) and larger fat
cells (0.90 +/- 0.26 vs. 0.78 +/- 0.17 microm; p = 0.04) as compared with obese
control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and
PPARgamma2, p = 0.02) had significantly lower expression in obese type 2
diabetics, whereas C/EBPbeta only tended to be lower (p = 0.07). DISCUSSION: This
cross-sectional study supports the hypothesis that impaired expression of
adipogenic genes may result in impaired adipogenesis, potentially leading to
larger fat cells in subcutaneous adipose tissue and insulin resistance.
PMID- 17030968
TI - Associations between aortic calcification and components of body composition in
elderly men.
AB - OBJECTIVE: To investigate associations among body composition, cardiovascular
risk factors, and atherosclerosis in middle-aged and elderly men for the
identification of potential pathogenic links. RESEARCH METHODS AND PROCEDURES:
The study included 168 white men 44 to 86 years old. Severity of aortic
calcification (AC) was graded on lateral radiographs, and body fat and lean mass
were measured by DXA. Information on demographic and lifestyle characteristics
also was gathered. RESULTS: A strong and independent inverse association was
found between AC and peripheral lean mass (PLM), even after adjusting for age and
BMI (p < 0.05). Independently of the influence of PLM, AC was directly correlated
with truncal fat mass (p < 0.05). Furthermore, AC was inversely associated with
tertiles of the free androgen index (p < 0.05). In a multiple regression model,
age and serum cholesterol (p < 0.01) contributed directly, and truncal fat mass
tended also to contribute directly (p = 0.09), whereas PLM contributed borderline
inversely (p = 0.06) to the variation of AC (R = 0.635, p < 0.0001). DISCUSSION:
Severity of AC is strongly dependent on age and further modulated by an array of
traditional cardiovascular risk factors. Sarcopenia and truncal fat mass are
reciprocal correlates of atherosclerosis of borderline statistical significance
in multivariate models. To clarify whether sarcopenia is an atherogenic risk
factor or rather a parallel consequence of low-grade inflammation also promoting
atherogenic trends, further longitudinal studies in larger sample sizes of men
and women are needed.
PMID- 17030969
TI - Cardiorespiratory fitness in youth: relationship to insulin sensitivity and beta
cell function.
AB - OBJECTIVE: We examined whether the relationship between cardiorespiratory fitness
(CRF) and insulin sensitivity (IS)/secretion is independent of adiposity in
healthy African-American (n = 65) and white (n = 57) youth. RESEARCH METHODS AND
PROCEDURES: IS and beta-cell function were evaluated by a 3-hour hyperinsulinemic
euglycemic and a 2-hour hyperglycemic (12.5 mM) clamp, respectively. Total fat
was measured by DXA and abdominal fat with computed tomography. CRF (peak volume
of oxygen) was measured using a graded maximal treadmill test. RESULTS:
Independent of race, CRF was inversely (p < 0.05) related to total and abdominal
fat, fasting insulin and first phase insulin secretion, and positively (p < 0.05)
related to IS. When subjects were categorized into low (< or = 50th) and high (>
50th) CRF groups, IS was significantly (p < 0.05) higher in the high compared
with the low CRF group independently of race. Furthermore, first and second phase
insulin secretion were lower (p < 0.05) in the high CRF group in comparison with
the low CRF group in both races. However, in multiple regression analyses CRF was
not (p > 0.05) an independent predictor of IS and acute insulin secretion after
accounting for total adiposity. DISCUSSION: Our findings demonstrate that low CRF
is associated with decreased IS compensated by higher insulin secretion in both
African-American and white youth. However, this relationship disappears after
adjusting for differences in adiposity, suggesting that the association between
fitness and IS is mediated, at least in part, through fatness.
PMID- 17030970
TI - Angiotensin-converting enzyme inhibition reduces lipid deposits in myocardium and
improves left ventricular function of obese zucker rats.
AB - OBJECTIVE: Alterations in the renin angiotensin system, cardiac lipotoxicity, and
left ventricular (LV) dysfunction have been reported in obese rats. The present
study examined whether angiotensin-converting enzyme inhibition could ameliorate
lipid deposition and ventricular function in the myocardium of obese Zucker rats
(OZRs). RESEARCH METHODS AND PROCEDURES: For 6 months, rats were treated as
follows: Group (G) 1, OZR, no treatment; G2, OZR + ramipril (R); G3, OZR +
amlodipine (AML); and G4, lean Zucker rats. LV function was assessed by
echocardiogram and lipid deposits in cardiomyocytes (LDCM) by light microscopy
using Oil red O. RESULTS: At the end of the experiment, both OZR + R and OZR +
AML groups presented similar reduction in blood pressure in comparison with
untreated OZR (p < 0.01). OZR with R presented lower insulin-to-glucose ratio and
lower serum triglycerides and cholesterol when compared with both untreated OZR
and OZR with AML (p < 0.01). Fractional shortening by echocardiogram was as
follows: G1, 25.4 +/- 3.8 (vs. G2 and G4, p < 0.05); G2, 37.2 +/- 2.4; G3, 29.3
+/- 4.4 (vs. G2 and G4, p < 0.05); and G4, 40.8 +/- 2.3. Percentage LDCM was as
follows: G1, 12.4 +/- 2.7 (vs. G2 and G4, p < 0.05); G2, 0.8 +/- 0.2; G3, 11.1 +/
2.1 (vs. G2 and G4, p < 0.05); and G4, 0.1 +/- 0.1. There was a negative
correlation between fractional shortening and LDCM percentage in OZR (r = -0.93)
and in OZR + AML (r = -0.87). DISCUSSION: AML reduced blood pressure
significantly; however, it failed to modify both metabolic parameters and LDCM.
In contrast, R showed a substantial reduction in LDCM, together with LV function
preservation.
PMID- 17030971
TI - A quantitative trait locus on chromosome 18q for physical activity and dietary
intake in Hispanic children.
AB - OBJECTIVE: Genetic components of energy homeostasis contributing to childhood
obesity are poorly understood. Genome scans were performed to identify
chromosomal regions contributing to physical activity and dietary intake traits
in Hispanic children participating in the VIVA LA FAMILIA Study. RESEARCH METHODS
AND PROCEDURES: We report linkage findings on chromosome 18 for physical activity
and dietary intake in 1030 siblings from 319 Hispanic families. Measurements
entailed physical activity by accelerometry, dietary intake by two 24-hour
recalls, and genetic linkage analyses using SOLAR software. RESULTS: Significant
heritabilities were seen for physical activity and dietary intake, ranging from
0.46 to 0.69, except for vigorous activity (h2 = 0.18). Percentage time in
sedentary activity mapped to markers D18S1102-D18S64 on chromosome 18 [logarithm
of the odds (LOD) score = 4.07], where melanocortin 4 receptor gene (MC4R)
resides. Quantitative trait loci (QTLs) for total activity counts, percentage
time in light or in moderate activity, and carbohydrate intake and percentage of
energy intake from carbohydrates were detected in the same region (LOD = 2.28,
2.79, 2.2, 1.84, and 1.51, respectively). A novel loss of function mutation in
MC4R (G55V) was detected in six obese relatives, but not in the rest of the
cohort. Removal of these MC4R-deficient subjects from the analysis reduced the
LOD score for sedentary activity to 3.94. DISCUSSION: Given its role in the
regulation of food intake and energy expenditure, MC4R is a strong positional
candidate gene for the QTL on chromosome 18 detected for physical activity and
dietary intake in Hispanic children.
PMID- 17030972
TI - A quantitative trait locus for body fat on chromosome 1q43 in French Canadians:
linkage and association studies.
AB - OBJECTIVE: To explore a quantitative trait locus (QTL) on human chromosome 1q
affecting BMI, adiposity, and fat-free mass phenotypes in the Quebec Family Study
cohort. RESEARCH METHODS AND PROCEDURES: Non-parametric sibpair and variance
component linkage analyses and family-based association studies were performed
with a dense set of chromosome 1q43 microsatellites and single-nucleotide
polymorphism markers in 885 adult individuals. RESULTS: Linkage was observed
between marker D1S184 and BMI (p = 0.0004) and with body fat mass or percentage
body fat (p < or = 0.0003), but no linkage was detected with fat-free mass.
Furthermore, significant linkages (p < 0.0001) were achieved with subsamples of
sibpairs at both ends of phenotype distributions. Association studies with
quantitative transmission disequilibrium tests refined the linkage to a region
overlapping the regulator of G-protein signaling 7 (RGS7) gene and extending to
immediate upstream gene loci. DISCUSSION: The present study indicates that the
QTL on chromosome 1q43 specifically affects total adiposity and provides a
genetic mapping framework for the dissection of this adiposity locus.
PMID- 17030973
TI - Hip-Hop to Health Jr. for Latino preschool children.
AB - OBJECTIVE: Hip-Hop to Health Jr. was a diet/physical activity intervention
designed to reduce gains in BMI (kilograms per meter squared) in preschool
minority children. RESEARCH METHODS AND PROCEDURES: Twelve predominantly Latino
Head Start centers participated in a group-randomized trial conducted between
Fall 2001 and Winter 2003. Six centers were randomized to a culturally proficient
14-week (three times weekly) diet/physical activity intervention. Parents
participated by completing weekly homework assignments. The children in the other
six centers received a general health intervention that did not address either
diet or physical activity. The primary outcome was change in BMI, and secondary
outcomes were changes in dietary intake and physical activity. Measures were
collected at baseline, post-intervention, and at Years 1 and 2 follow-up.
RESULTS: There were no significant differences between intervention and control
schools in either primary or secondary outcomes at post-intervention, Year 1, or
Year 2 follow-ups. DISCUSSION: When Hip-Hop to Health Jr. was conducted in
predominantly black Head Start centers, it was effective in reducing subsequent
increases in BMI in preschool children. In contrast, when the program was
conducted in Latino centers, it was not effective. Although the intervention did
not prevent excessive weight gain in Latino children, it was very well received.
Future interventions with this population may require further cultural tailoring
and a more robust parent intervention.
PMID- 17030974
TI - Body image and quality of life in post massive weight loss body contouring
patients.
AB - OBJECTIVE: Because post-bariatric surgery patients undergo massive weight loss,
the resulting skin excess can lead to both functional problems and profound
dissatisfaction with appearance. Correcting skin excess could improve all these
corollaries, including body image. Presently, few data are available documenting
body image and weight-related quality of life in this population. RESEARCH
METHODS AND PROCEDURES: Eighteen patients who underwent both bariatric surgery
and body contouring completed our study. Both established surveys and new surveys
designed specifically for the study were used to assess body perception and
ideals, quality of life, and mood. Patients were surveyed at the following time
points: pre-body contouring (after massive weight loss) and both 3 and 6 month
post-body contouring. Statistical testing was performed using Student's t test
and ANOVA. RESULTS: The mean age of the patients was 46 +/- 10 years (standard
deviation). Quality of life improved after obesity surgery and was significantly
enhanced after body contouring. Three months after body contouring, subjects
ascribed thinner silhouettes to both current appearance and ideal body image.
Body image also improved with body contouring surgery. Mood remained stable over
6 months. DISCUSSION: Body contouring after surgical weight loss improved both
quality-of-life measurements and body image. Initial body dissatisfaction did not
correlate with mood. Body contouring improved body image but produced
dissatisfaction with other parts of the body, suggesting that as patients become
closer to their ideal, these ideals may shift. We further developed several new
assessment methods that may prove useful in understanding these post-surgical
weight loss patients.
PMID- 17030975
TI - Long-term effects of obesity on employment and work limitations among U.S.
Adults, 1986 to 1999.
AB - OBJECTIVE: To determine the relationships between BMI and workforce participation
and the presence of work limitations in a U.S. working-age population. RESEARCH
METHODS AND PROCEDURES: We used data from the Panel Study of Income Dynamics, a
nationwide prospective cohort, to estimate the effect of obesity in 1986 on
employment and work limitations in 1999. Individuals were classified into the
following weight categories: underweight (BMI < 18.5), normal weight (18.5 < or =
BMI < 25), overweight (25 < or = BMI < 30), and obese (BMI > or = 30). Using
multivariable probit models, we estimated the relationships between obesity and
both employment and work disability. All analyses were stratified by sex.
RESULTS: After adjusting for baseline sociodemographic characteristics, smoking
status, exercise, and self-reported health, obesity was associated with reduced
employment at follow-up [men: marginal effect (ME) -4.8 percentage points (pp); p
< 0.05; women: ME -5.8 pp; p < 0.10]. Among employed women, being either
overweight or obese was associated with an increase in self-reported work
limitations when compared with normal-weight individuals (overweight: ME +3.9 pp;
p < 0.01; obese: ME +12.6 pp; p < 0.01). Among men, the relationship between
obesity and work limitations was not statistically significant. DISCUSSION:
Obesity appears to result in future productivity losses through reduced workforce
participation and increased work limitations. These findings have important
implications in the U.S., which is currently experiencing a rise in the
prevalence of obesity.
PMID- 17030976
TI - Maternal corticotropin-releasing hormone levels during pregnancy and offspring
adiposity.
AB - OBJECTIVE: Animal models suggest that fetal exposure to glucocorticoids can
program adiposity, especially central adiposity, later in life. We examined
associations of maternal corticotropin-releasing hormone (CRH) levels in the late
2nd trimester of pregnancy, a marker of fetal glucocorticoid exposure, with child
adiposity at age 3 years. RESEARCH METHODS AND PROCEDURES: We analyzed data from
199 participants in Project Viva, a prospective cohort study of pregnant women
and their children, At age 3 years, the main outcomes were age-sex-specific BMI z
score and the sum of subscapular (SS) and triceps (TR) skinfold thicknesses to
represent overall adiposity, and ratio of SS to TR (SS:TR) to represent central
adiposity. RESULTS: Mean (standard deviation) maternal 2nd trimester log CRH was
4.94 (0.56) pg/mL. At age 3, mean (standard deviation) for BMI z score was 0.52
(1.02); for SS + TR, 16.51 (3.94) mm; and for SS:TR, 0.67 (0.17). Log CRH was
mildly inversely correlated with birth weight (r = -0.08), chiefly because of its
association with length of gestation (r = -0.21) rather than fetal growth (r =
0.004). After adjustment for sociodemographic factors, maternal smoking, BMI, and
gestational weight gain, fetal growth, length of gestation, breastfeeding
duration, and (for SS:TR only) child's 3-year BMI, each increment of 1 unit of
log CRH was associated with a reduction in BMI z score [-0.43; 95% confidence
interval (CI), -0.73, -0.14; p = 0.004] and possible reduction in SS + TR (-1.10;
95% CI, -2.33, 0.14; p = 0.08). In contrast, log CRH was associated with higher
SS:TR (0.07; 95% CI, 0.02, 0.13; p = 0.007). DISCUSSION: Fetal exposure to
glucocorticoids, although associated with an overall decrease in body size, may
cause an increase in central adiposity.
PMID- 17030977
TI - Impaired lung function is associated with obesity and metabolic syndrome in
adults.
AB - OBJECTIVE: Impaired lung function is associated with obesity and insulin
resistance. In this study, we investigated the relationship between metabolic
syndrome and impaired lung function in adults. RESEARCH METHODS AND PROCEDURES: A
total of 46,514 subjects 20 years and over (21,669 men and 24,845 women, mean age
= 37.3 +/- 11.2 and 37.0 +/- 11.3 years, respectively) were recruited from four
nationwide MJ Health Screening Centers in Taiwan from 1998 to 2000. Metabolic
syndrome was defined using the National Cholesterol Education Panel (NCEP)
metabolic syndrome criteria or America Heart Association/National Heart Lung
Blood Institute (AHA/NHLBI) criteria. The relationship between metabolic syndrome
and lung function test was examined using multivariate logistic regression
analysis. RESULTS: The prevalence of impaired lung function was 11.1% in men and
14.0% in women. The prevalence of metabolic syndrome was 5.8% using NCEP criteria
and 12.8% using AHA/NHLBI criteria. In multivariate logistic regression analysis
with adjustment for age, gender, BMI, smoking, alcohol drinking, and physical
activity, restrictive lung impairment was independently associated with increased
risk of having metabolic syndrome (p < 0.01, odds ratios = 1.221 using NCEP
criteria and 1.150 using AHA/NHLBI criteria). DISCUSSION: Obesity and metabolic
syndrome were associated with impaired lung function in adults in Taiwan. Our
results imply that obesity and insulin resistance may be the common pathways
underlying lung function impairment and metabolic syndrome. Moreover, lung
function test may be applied as an additional evaluation for metabolic syndrome
in a clinical setting.
PMID- 17030978
TI - Relation of BMI and physical activity to sex hormones in postmenopausal women.
AB - OBJECTIVE: Levels of estrogen, androgen, and prolactin have been related to risk
of postmenopausal breast cancer. However, the determinants of these hormone
concentrations are not established. The purpose of this study was to examine
correlates of endogenous sex hormones. RESEARCH METHODS AND PROCEDURES:
Associations among adiposity, physical activity, and diet and concentrations of
estradiol, free estradiol, estrone, testosterone, free testosterone, sex hormone
binding globulin (SHBG), androstenedione, dehydroepiandrosterone,
dehydroepiandrosterone sulfate, and prolactin were evaluated in 267
postmenopausal women randomly selected from the Women's Health Initiative Dietary
Modification Trial. RESULTS: In multiple regression analyses on log-transformed
hormones, BMI was positively associated with estrone (beta = 0.031, p < 0.001),
estradiol (beta = 0.048, p < 0.001), free estradiol (beta = 0.062, p < 0.001),
free testosterone (beta = 0.017, p = 0.02), and prolactin (beta = 0.012, p =
0.02) and negatively associated with SHBG (beta = -0.02, p = 0.001). Total
physical activity (metabolic equivalent tasks per week) was negatively associated
with concentrations of estrone, estradiol, and androstenedione (beta = -0.006,
0.007, and -0.005, respectively, all p < or = 0.05). Using a composite variable
of BMI and physical activity dichotomized by median values, women with high
BMI/low physical activity had a mean estrone concentration of 28.8 pg/mL,
compared with 24.1, 19.9, and 18.4 pg/mL for women with high BMI/high physical
activity, low BMI/low physical activity, and low BMI/high physical activity,
respectively (p trend < 0.001). Similar trends were observed for estradiol and
free estradiol and, in inverse, for SHBG. DISCUSSION: These associations may, in
part, explain the positive associations between overweight/obesity and a
sedentary lifestyle on breast cancer risk.
PMID- 17030979
TI - Full of sound and fury, but signifying something: XVI International AIDS
Conference, Toronto, Canada, August 13-18, 2006.
AB - The biennial AIDS conference is often exhausting and irritating, but it offers a
unique view of how science and society interact. It still deserves the support of
basic scientists.
PMID- 17030980
TI - Dynamic microtubules are essential for efficient chromosome capture and
biorientation in S. cerevisiae.
AB - Attachment of chromosomes to the mitotic spindle has been proposed to require
dynamic microtubules that randomly search three-dimensional space and become
stabilized upon capture by kinetochores. In this study, we test this model by
examining chromosome capture in Saccharomyces cerevisiae mutants with attenuated
microtubule dynamics. Although viable, these cells are slow to progress through
mitosis. Preanaphase cells contain a high proportion of chromosomes that are
attached to only one spindle pole and missegregate in the absence of the spindle
assembly checkpoint. Measurement of the rates of chromosome capture and
biorientation demonstrate that both are severely decreased in the mutants. These
results provide direct evidence that dynamic microtubules are critical for
efficient chromosome capture and biorientation and support the hypothesis that
microtubule search and capture plays a central role in assembly of the mitotic
spindle.
PMID- 17030981
TI - Mapping the assembly pathways that specify formation of the trilaminar
kinetochore plates in human cells.
AB - We report the interactions amongst 20 proteins that specify their assembly to the
centromere-kinetochore complex in human cells. Centromere protein (CENP)-A is at
the top of a hierarchy that directs three major pathways, which are specified by
CENP-C, -I, and Aurora B. Each pathway consists of branches that intersect to
form nodes that may coordinate the assembly process. Complementary EM studies
found that the formation of kinetochore trilaminar plates depends on the CENP
I/NUF2 branch, whereas CENP-C and Aurora B affect the size, shape, and structural
integrity of the plates. We found that hMis12 is not constitutively localized at
kinetochores, and that it is not essential for recruiting CENP-I. Our studies
also revealed that kinetochores in HeLa cells contain an excess of CENP-A, of
which approximately 10% is sufficient to promote the assembly of normal levels of
kinetochore proteins. We elaborate on a previous model that suggested
kinetochores are assembled from repetitive modules (Zinkowski, R.P., J. Meyne,
and B.R. Brinkley. 1991. J. Cell Biol. 113:1091-110).
PMID- 17030982
TI - Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response
to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and
ATR.
AB - The promyelocytic leukemia (PML) nuclear body (NB) is a dynamic subnuclear
compartment that is implicated in tumor suppression, as well as in the
transcription, replication, and repair of DNA. PML NB number can change during
the cell cycle, increasing in S phase and in response to cellular stress,
including DNA damage. Although topological changes in chromatin after DNA damage
may affect the integrity of PML NBs, the molecular or structural basis for an
increase in PML NB number has not been elucidated. We demonstrate that after DNA
double-strand break induction, the increase in PML NB number is based on a
biophysical process, as well as ongoing cell cycle progression and DNA repair.
PML NBs increase in number by a supramolecular fission mechanism similar to that
observed in S-phase cells, and which is delayed or inhibited by the loss of
function of NBS1, ATM, Chk2, and ATR kinase. Therefore, an increase in PML NB
number is an intrinsic element of the cellular response to DNA damage.
PMID- 17030983
TI - Visualization of mRNA translation in living cells.
AB - The role of mRNA localization is presumably to effect cell asymmetry by
synthesizing proteins in specific cellular compartments. However, protein
synthesis has never been directly demonstrated at the sites of mRNA localization.
To address this, we developed a live cell method for imaging translation of beta
actin mRNA. Constructs coding for beta-actin, containing tetracysteine motifs,
were transfected into C2C12 cells, and sites of nascent polypeptide chains were
detected using the biarsenial dyes FlAsH and ReAsH, a technique we call
translation site imaging. These sites colocalized with beta-actin mRNA at the
leading edge of motile myoblasts, confirming that they were translating. beta
Actin mRNA lacking the sequence (zipcode) that localizes the mRNA to the cell
periphery, eliminated the translation there. A pulse-chase experiment on living
cells showed that the recently synthesized protein correlated spatially with the
sites of its translation. Additionally, localization of beta-actin mRNA and
translation activity was enhanced at cell contacts and facilitated the formation
of intercellular junctions.
PMID- 17030984
TI - MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206.
AB - Terminal differentiation of distinct cell types requires the transcriptional
activation of differentiation-specific genes and the suppression of genes
associated with the precursor cell. For example, the expression of utrophin
(Utrn) is suppressed during skeletal muscle differentiation, and it is replaced
at the sarcolemma by the related dystrophin protein. The MyoD transcription
factor directly activates the expression of a large number of skeletal muscle
genes, but also suppresses the expression of many genes. To characterize a
mechanism of MyoD-mediated suppression of gene expression, we investigated two
genes that are suppressed in fibroblasts converted to skeletal muscle by MyoD,
follistatin-like 1 (Fstl1) and Utrn. MyoD directly activates the expression of a
muscle-specific microRNA (miRNA), miR-206, which targets sequences in the Fstl1
and Utrn RNA, and these sequences are sufficient to suppress gene expression in
the presence of miR-206. These findings demonstrate that MyoD, in addition to
activating muscle-specific genes, induces miRNAs that repress gene expression
during skeletal muscle differentiation.
PMID- 17030985
TI - Shootin1: A protein involved in the organization of an asymmetric signal for
neuronal polarization.
AB - Neurons have the remarkable ability to polarize even in symmetrical in vitro
environments. Although recent studies have shown that asymmetric intracellular
signals can induce neuronal polarization, it remains unclear how these polarized
signals are organized without asymmetric cues. We describe a novel protein, named
shootin1, that became up-regulated during polarization of hippocampal neurons and
began fluctuating accumulation among multiple neurites. Eventually, shootin1
accumulated asymmetrically in a single neurite, which led to axon induction for
polarization. Disturbing the asymmetric organization of shootin1 by excess
shootin1 disrupted polarization, whereas repressing shootin1 expression inhibited
polarization. Overexpression and RNA interference data suggest that shootin1 is
required for spatially localized phosphoinositide-3-kinase activity. Shootin1 was
transported anterogradely to the growth cones and diffused back to the soma;
inhibiting this transport prevented its asymmetric accumulation in neurons. We
propose that shootin1 is involved in the generation of internal asymmetric
signals required for neuronal polarization.
PMID- 17030986
TI - Embryonic cortical neural stem cells migrate ventrally and persist as postnatal
striatal stem cells.
AB - Embryonic cortical neural stem cells apparently have a transient existence, as
they do not persist in the adult cortex. We sought to determine the fate of
embryonic cortical stem cells by following Emx1(IREScre); LacZ/EGFP double
transgenic murine cells from midgestation into adulthood. Lineage tracing in
combination with direct cell labeling and time-lapse video microscopy
demonstrated that Emx1-lineage embryonic cortical stem cells migrate ventrally
into the striatal germinal zone (GZ) perinatally and intermingle with striatal
stem cells. Upon integration into the striatal GZ, cortical stem cells down
regulate Emx1 and up-regulate Dlx2, which is a homeobox gene characteristic of
the developing striatum and striatal neural stem cells. This demonstrates the
existence of a novel dorsal-to-ventral migration of neural stem cells in the
perinatal forebrain.
PMID- 17030987
TI - Transient anchorage of cross-linked glycosyl-phosphatidylinositol-anchored
proteins depends on cholesterol, Src family kinases, caveolin, and
phosphoinositides.
AB - How outer leaflet plasma membrane components, including glycosyl
phosphatidylinositol-anchored proteins (GPIAPs), transmit signals to the cell
interior is an open question in membrane biology. By deliberately cross-linking
several GPIAPs under antibody-conjugated 40-nm gold particles, transient
anchorage of the gold particle-induced clusters of both Thy-1 and CD73, a 5'
exonucleotidase, occurred for periods ranging from 300 ms to 10 s in fibroblasts.
Transient anchorage was abolished by cholesterol depletion, addition of the Src
family kinase (SFK) inhibitor PP2, or in Src-Yes-Fyn knockout cells. Caveolin-1
knockout cells exhibited a reduced transient anchorage time, suggesting the
partial participation of caveolin-1. In contrast, a transmembrane protein, the
cystic fibrosis transmembrane conductance regulator, exhibited transient
anchorage that occurred without deliberately enhanced cross-linking; moreover, it
was only slightly inhibited by cholesterol depletion or SFK inhibition and
depended completely on the interaction of its PDZ-binding domain with the
cytoskeletal adaptor EBP50. We propose that cross-linked GPIAPs become
transiently anchored via a cholesterol-dependent SFK-regulatable linkage between
a transmembrane cluster sensor and the cytoskeleton.
PMID- 17030988
TI - Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and
pericyte TIMP-3.
AB - The endothelial cell (EC)-derived tissue inhibitor of metalloproteinase-2 (TIMP
2) and pericyte-derived TIMP-3 are shown to coregulate human capillary tube
stabilization following EC-pericyte interactions through a combined ability to
block EC tube morphogenesis and regression in three-dimensional collagen
matrices. EC-pericyte interactions strongly induce TIMP-3 expression by
pericytes, whereas ECs produce TIMP-2 in EC-pericyte cocultures. Using small
interfering RNA technology, the suppression of EC TIMP-2 and pericyte TIMP-3
expression leads to capillary tube regression in these cocultures in a matrix
metalloproteinase-1 (MMP-1)-, MMP-10-, and ADAM-15 (a disintegrin and
metalloproteinase-15)-dependent manner. Furthermore, we show that EC tube
morphogenesis (lumen formation and invasion) is primarily controlled by the TIMP
2 and -3 target membrane type (MT) 1 MMP. Additional targets of these inhibitors
include MT2-MMP and ADAM-15, which also regulate EC invasion. Mutagenesis
experiments reveal that TIMP-3 requires its proteinase inhibitory function to
induce tube stabilization. Overall, these data reveal a novel role for both TIMP
2 and -3 in the pericyte-induced stabilization of newly formed vascular networks
that are predisposed to undergo regression and reveal specific molecular targets
of the inhibitors regulating these events.
PMID- 17030989
TI - Growth and developmental control in the model and pathogenic aspergilli.
PMID- 17030990
TI - Upstream and downstream regulation of asexual development in Aspergillus
fumigatus.
AB - The opportunistic human pathogen Aspergillus fumigatus produces a large quantity
of asexual spores (conidia), which are the primary agent causing invasive
aspergillosis in immunocompromised patients. We investigated the mechanisms
controlling asexual sporulation (conidiation) in A. fumigatus via examining
functions of four key regulators, GpaA (Galpha), AfFlbA (RGS), AfFluG, and
AfBrlA, previously studied in Aspergillus nidulans. Expression analyses of gpaA,
AfflbA, AffluG, AfbrlA, and AfwetA throughout the life cycle of A. fumigatus
revealed that, while transcripts of AfflbA and AffluG accumulate constantly, the
latter two downstream developmental regulators are specifically expressed during
conidiation. Both loss-of-function AfflbA and dominant activating GpaA(Q204L)
mutations resulted in reduced conidiation with increased hyphal proliferation,
indicating that GpaA signaling activates vegetative growth while inhibiting
conidiation. As GpaA is the primary target of AfFlbA, the dominant interfering
GpaA(G203R) mutation suppressed reduced conidiation caused by loss of AfflbA
function. These results corroborate the hypothesis that functions of G proteins
and RGSs are conserved in aspergilli. We then examined functions of the two major
developmental activators AfFluG and AfBrlA. While deletion of AfbrlA eliminated
conidiation completely, null mutation of AffluG did not cause severe alterations
in A. fumigatus sporulation in air-exposed culture, implying that, whereas the
two aspergilli may have a common key downstream developmental activator, upstream
mechanisms activating brlA may be distinct. Finally, both AffluG and AfflbA
mutants showed reduced conidiation and delayed expression of AfbrlA in
synchronized developmental induction, indicating that these upstream regulators
contribute to the proper progression of conidiation.
PMID- 17030991
TI - The intracellular siderophore ferricrocin is involved in iron storage, oxidative
stress resistance, germination, and sexual development in Aspergillus nidulans.
AB - Iron is required by most organisms, but an excess of this metal is potentially
toxic. Consequently, uptake and intracellular storage of iron are tightly
controlled. The filamentous fungus A. nidulans lacks the iron storage compound
ferritin but possesses an intracellular siderophore, which is accumulated in a
highly regulated manner as iron-free desferri-ferricrocin or iron-containing
ferricrocin via transcriptional regulation of the nonribosomal peptide synthetase
SidC. Biosynthesis of desferri-ferricrocin was low during iron-replete conditions
but up-regulated by both iron starvation and intracellular iron excess, the
latter caused by either a shift from iron-depleted to high-iron conditions or
deregulation of iron uptake. Consequently, ferricrocin constituted only about 5%
of the total iron content under iron-replete conditions but up to 64% during
conditions of intracellular excess. In contrast, during iron starvation, desferri
ferricrocin was accumulated, which appears to represent a proactive strategy to
prevent iron toxicity. Accumulation of the intracellular siderophore was also up
regulated by oxidative stress, which underscores the intertwining of iron
metabolism and oxidative stress. Lack of the intracellular siderophore causes
pleiotropic effects, as SidC deficiency results in (i) less-efficient utilization
of iron, indicated by reduced growth under iron-depleted conditions and a higher
iron demand under iron-replete conditions, (ii) delayed germination under iron
depleted conditions, (iii) increased sensitivity of conidia to oxidative stress,
and (iv) elimination of cleistothecia formation in homothallic conditions.
PMID- 17030992
TI - Function of Candida albicans adhesin Hwp1 in biofilm formation.
AB - Hwp1 is a well-characterized Candida albicans cell surface protein, expressed
only on hyphae, that mediates tight binding to oral epithelial cells. Prior
studies indicate that HWP1 expression is dependent upon Bcr1, a key regulator of
biofilm formation. Here we test the hypothesis that Hwp1 is required for biofilm
formation. In an in vitro model, the hwp1/hwp1 mutant produces a thin biofilm
that lacks much of the hyphal mass found in the hwp1/HWP1 reconstituted strain.
In a biofilm cell retention assay, we find that the hwp1/hwp1 mutant is defective
in retention of nonadherent bcr1/bcr1 mutant cells. In an in vivo rat venous
catheter model, the hwp1/hwp1 mutant has a severe biofilm defect, yielding only
yeast microcolonies in the catheter lumen. These properties of the hwp1/hwp1
mutant are consistent with its role as a hypha-specific adhesin and indicate that
it is required for normal biofilm formation. Overexpression of HWP1 in a
bcr1/bcr1 mutant background improves adherence in the in vivo catheter model.
This finding provides additional support for the model that Hwp1 is critical for
biofilm adhesion. Hwp1 is the first cell surface protein known to be required for
C. albicans biofilm formation in vivo and is thus an excellent therapeutic
target.
PMID- 17030993
TI - Gis4, a new component of the ion homeostasis system in the yeast Saccharomyces
cerevisiae.
AB - Gis4 is a new component of the system required for acquisition of salt tolerance
in Saccharomyces cerevisiae. The gis4Delta mutant is sensitive to Na(+) and Li(+)
ions but not to osmotic stress. Genetic evidence suggests that Gis4 mediates its
function in salt tolerance, at least partly, together with the Snf1 protein
kinase and in parallel with the calcineurin protein phosphatase. When exposed to
salt stress, mutants lacking gis4Delta display a defect in maintaining low
intracellular levels of Na(+) and Li(+) ions and exporting those ions from the
cell. This defect is due to diminished expression of the ENA1 gene, which encodes
the Na(+) and Li(+) export pump. The protein sequence of Gis4 is poorly conserved
and does not reveal any hints to its molecular function. Gis4 is enriched at the
cell surface, probably due to C-terminal farnesylation. The CAAX box at the C
terminus is required for cell surface localization but does not seem to be
strictly essential for the function of Gis4 in salt tolerance. Gis4 and Snf1 seem
to share functions in the control of ion homeostasis and ENA1 expression but not
in glucose derepression, the best known role of Snf1. Together with additional
evidence that links Gis4 genetically and physically to Snf1, it appears that Gis4
may function in a pathway in which Snf1 plays a specific role in controlling ion
homeostasis. Hence, it appears that the conserved Snf1 kinase plays roles in
different pathways controlling nutrient as well as stress response.
PMID- 17030994
TI - Identification of PhIL1, a novel cytoskeletal protein of the Toxoplasma gondii
pellicle, through photosensitized labeling with 5-[125I]iodonaphthalene-1-azide.
AB - The pellicle of the protozoan parasite Toxoplasma gondii is a unique triple
bilayer structure, consisting of the plasma membrane and two tightly apposed
membranes of the underlying inner membrane complex. Integral membrane proteins of
the pellicle are likely to play critical roles in host cell recognition,
attachment, and invasion, but few such proteins have been identified. This is in
large part because the parasite surface is dominated by a family of abundant and
highly immunogenic glycosylphosphatidylinositol (GPI)-anchored proteins, which
has made the identification of non-GPI-linked proteins difficult. To identify
such proteins, we have developed a radiolabeling approach using the hydrophobic,
photoactivatable compound 5-[(125)I]iodonaphthalene-1-azide (INA). INA can be
activated by photosensitizing fluorochromes; by restricting these fluorochromes
to the pellicle, [(125)I]INA labeling will selectively target non-GPI-anchored
membrane-embedded proteins of the pellicle. We demonstrate here that three known
membrane proteins of the pellicle can indeed be labeled by photosensitization
with INA. In addition, this approach has identified a novel 22-kDa protein, named
PhIL1 (photosensitized INA-labeled protein 1), with unexpected properties. While
the INA labeling of PhIL1 is consistent with an integral membrane protein, the
protein has neither a transmembrane domain nor predicted sites of lipid
modification. PhIL1 is conserved in apicomplexan parasites and localizes to the
parasite periphery, concentrated at the apical end just basal to the conoid.
Detergent extraction and immunolocalization data suggest that PhIL1 associates
with the parasite cytoskeleton.
PMID- 17030995
TI - Transcriptome analysis of Aspergillus nidulans exposed to camptothecin-induced
DNA damage.
AB - We have used an Aspergillus nidulans macroarray carrying sequences of 2,787 genes
from this fungus to monitor gene expression of both wild-type and uvsB(ATR) (the
homologue of the ATR gene) deletion mutant strains in a time course exposure to
camptothecin (CPT). The results revealed a total of 1,512 and 1,700 genes in the
wild-type and uvsB(ATR) deletion mutant strains that displayed a statistically
significant difference at at least one experimental time point. We characterized
six genes that have increased mRNA expression in the presence of CPT in the wild
type strain relative to the uvsB(ATR) mutant strain: fhdA (encoding a forkhead
associated domain protein), tprA (encoding a hypothetical protein that contains a
tetratrico peptide repeat), mshA (encoding a MutS homologue involved in mismatch
repair), phbA (encoding a prohibitin homologue), uvsC(RAD51) (the homologue of
the RAD51 gene), and cshA (encoding a homologue of the excision repair protein
ERCC-6 [Cockayne's syndrome protein]). The induced transcript levels of these
genes in the presence of CPT require uvsB(ATR). These genes were deleted, and
surprisingly, only the DeltauvsC mutant strain was sensitive to CPT; however, the
others displayed sensitivity to a range of DNA-damaging and oxidative stress
agents. These results indicate that the selected genes when inactivated display
very complex and heterogeneous sensitivity behavior during growth in the presence
of agents that directly or indirectly cause DNA damage. Moreover, with the
exception of UvsC, deletion of each of these genes partially suppressed the
sensitivity of the DeltauvsB strain to menadione and paraquat. Our results
provide the first insight into the overall complexity of the response to DNA
damage in filamentous fungi and suggest that multiple pathways may act in
parallel to mediate DNA repair.
PMID- 17030996
TI - Molecular studies reveal frequent misidentification of Aspergillus fumigatus by
morphotyping.
AB - Aspergillus fumigatus has been understood to be the most common cause of invasive
aspergillosis (IA) in all epidemiological surveys. However, recent studies have
uncovered a large degree of genetic heterogeneity between isolates
morphologically identified as A. fumigatus, leading to the description of a new
species, Aspergillus lentulus. Here, we examined the genetic diversity of
clinical isolates identified as A. fumigatus using restriction enzyme
polymorphism analysis and sequence-based identification. Analysis of 50 clinical
isolates from geographically diverse locations recorded the presence of at least
three distinct species: A. lentulus, Aspergillus udagawae, and A. fumigatus. In
vitro, A. lentulus isolates demonstrated decreased susceptibility to antifungal
drugs currently used for IA, including amphotericin B, voriconazole, and
caspofungin; A. udagawae isolates demonstrated decreased in vitro susceptibility
to amphotericin B. Results of the present study demonstrate that current
phenotypic methods to identify fungi do not differentiate between genetically
distinct species in the A. fumigatus group. Differential antifungal
susceptibilities of these species may account for some of the reported poor
outcomes of therapy in clinical studies.
PMID- 17030997
TI - Modulation of Leishmania ABC protein gene expression through life stages and
among drug-resistant parasites.
AB - The ATP-binding cassette (ABC) protein superfamily is one of the largest
evolutionarily conserved families and is found in all kingdoms of life. The
recent completion of the Leishmania genome sequence allowed us to analyze and
classify its encoded ABC proteins. The complete sequence predicts a data set of
42 open reading frames (ORFs) coding for proteins belonging to the ABC
superfamily, with representative members of every major subfamily (from ABCA to
ABCH) commonly found in eukaryotes. Comparative analysis showed that the same ABC
data set is found between Leishmania major and Leishmania infantum and that some
orthologues are found in the genome of the related parasites Trypanosoma brucei
and Trypanosoma cruzi. Customized DNA microarrays were made to assess ABC gene
expression profiling throughout the two main Leishmania life stages. Two ABC
genes (ABCA3 and ABCG3) are preferentially expressed in the amastigote stage,
whereas one ABC gene (ABCF3) is more abundantly expressed in promastigotes.
Microarray-based expression profiling experiments also revealed that three ABC
genes (ABCA3, ABCC3, and ABCH1) are overexpressed in two independent antimony
resistant strains compared to the parental sensitive strain. All microarray
results were confirmed by real-time reverse transcription-PCR assays. The present
study provides a thorough phylogenic classification of the Leishmania ABC
proteins and sets the basis for further functional studies on this important
class of proteins.
PMID- 17030998
TI - A glucose sensor in Candida albicans.
AB - The Hgt4 protein of Candida albicans (orf19.5962) is orthologous to the Snf3 and
Rgt2 glucose sensors of Saccharomyces cerevisiae that govern sugar acquisition by
regulating the expression of genes encoding hexose transporters. We found that
HGT4 is required for glucose induction of the expression of HGT12, HXT10, and
HGT7, which encode apparent hexose transporters in C. albicans. An hgt4Delta
mutant is defective for growth on fermentable sugars, which is consistent with
the idea that Hgt4 is a sensor of glucose and similar sugars. Hgt4 appears to be
sensitive to glucose levels similar to those in human serum ( approximately 5
mM). HGT4 expression is repressed by high levels of glucose, which is consistent
with the idea that it encodes a high-affinity sugar sensor. Glucose sensing
through Hgt4 affects the yeast-to-hyphal morphological switch of C. albicans
cells: hgt4Delta mutants are hypofilamented, and a constitutively signaling form
of Hgt4 confers hyperfilamentation of cells. The hgt4Delta mutant is less
virulent than wild-type cells in a mouse model of disseminated candidiasis. These
results suggest that Hgt4 is a high-affinity glucose sensor that contributes to
the virulence of C. albicans.
PMID- 17030999
TI - SWI/SNF displaces SAGA-acetylated nucleosomes.
AB - SWI/SNF is a well-characterized chromatin remodeling complex that remodels
chromatin by sliding nucleosomes in cis and/or displacing nucleosomes in trans.
The latter mechanism has the potential to remove promoter nucleosomes, allowing
access to transcription factors and RNA polymerase. In vivo, histone acetylation
often precedes apparent nucleosome loss; therefore, we sought to determine
whether nucleosomes containing acetylated histones could be displaced by the
SWI/SNF chromatin remodeling complex. We found that SAGA-acetylated histones were
lost from an immobilized nucleosome array when treated with the SWI/SNF complex.
When the nucleosome array was acetylated by SAGA in the presence of bound
transcription activators, it generated a peak of acetylation surrounding the
activator binding sites. Subsequent SWI/SNF treatment suppressed this acetylation
peak. Immunoblots indicated that SWI/SNF preferentially displaced acetylated
histones from the array relative to total histones. Moreover, the Swi2/Snf2
bromodomain, an acetyl-lysine binding domain, played a role in the displacement
of acetylated histones. These data indicate that targeted histone acetylation by
the SAGA complex predisposes promoter nucleosomes for displacement by the SWI/SNF
complex.
PMID- 17031000
TI - Cooperation between reverse transcriptase and integrase during reverse
transcription and formation of the preintegrative complex of Ty1.
AB - Reverse transcriptase (RT) and integrase (IN) play a central role in the
replication and transposition of retroelements. Increasing evidence suggests that
the interaction between these two enzymes is functional and plays an important
role in replication. In the yeast Saccharomyces cerevisiae retrotransposon Ty1,
the interaction of IN with RT is critical for the formation of an active
conformation of RT. We show here that the RT associated with VLPs is active only
if it is in close interaction with IN. To probe the IN-RT cis-trans relationship,
we have used a complementation assay based on coexpressing two transposons. We
show that IN acts in cis to activate RT and that a functional integrase provided
in trans is not able to complement replication and transposition defects of IN
deletion or IN active-site mutant elements. Our data support a model in which IN
not only interacts closely with RT during reverse transcription but also remains
associated with RT during the formation of the preintegrative complex.
PMID- 17031001
TI - Function of the Dictyostelium discoideum Atg1 kinase during autophagy and
development.
AB - When starved, the amoebae of Dictyostelium discoideum initiate a developmental
process that results in the formation of fruiting bodies in which stalks support
balls of spores. The nutrients and energy necessary for development are provided
by autophagy. Atg1 is a protein kinase that regulates the induction of autophagy
in the budding yeast Saccharomyces cerevisiae. In addition to a conserved kinase
domain, Dictyostelium Atg1 has a C-terminal region that has significant homology
to the Caenorhabditis elegans and mammalian Atg1 homologues but not to the
budding yeast Atg1. We investigated the function of the kinase and conserved C
terminal domains of D. discoideum Atg1 (DdAtg1) and showed that these domains are
essential for autophagy and development. Kinase-negative DdAtg1 acts in a
dominant-negative fashion, resulting in a mutant phenotype when expressed in the
wild-type cells. Green fluorescent protein-tagged kinase-negative DdAtg1
colocalizes with red fluorescent protein (RFP)-tagged DdAtg8, a marker of
preautophagosomal structures and autophagosomes. The conserved C-terminal region
is essential for localization of kinase-negative DdAtg1 to autophagosomes labeled
with RFP-tagged Dictyostelium Atg8. The dominant-negative effect of the kinase
defective mutant also depends on the C-terminal domain. In cells expressing
dominant-negative DdAtg1, autophagosomes are formed and accumulate but seem not
to be functional. By using a temperature-sensitive DdAtg1, we showed that DdAtg1
is required throughout development; development halts when the cells are shifted
to the restrictive temperature, but resumes when cells are returned to the
permissive temperature.
PMID- 17031003
TI - A putative Ariadne-like ubiquitin ligase is required for Dictyostelium discoideum
development.
AB - The Dictyostelium rbrA gene encodes a putative Ariadne ubiquitin ligase. rbrA(-)
cells form defective slugs that cannot phototax. Prestalk cell numbers are
reduced in rbrA(-) slugs, and these prestalk cells do not localize to the tip of
slugs. Chimeric slugs containing wild-type cells could phototax and form fruiting
bodies.
PMID- 17031002
TI - Role of the Fusarium fujikuroi TOR kinase in nitrogen regulation and secondary
metabolism.
AB - In Fusarium fujikuroi, the biosynthesis of gibberellins (GAs) and bikaverin is
under control of AreA-mediated nitrogen metabolite repression. Thus far, the
signaling components acting upstream of AreA and regulating its nuclear
translocation are unknown. In Saccharomyces cerevisiae, the target of rapamycin
(TOR) proteins, Tor1p and Tor2p, are key players of nutrient-mediated signal
transduction to control cell growth. In filamentous fungi, probably only one TOR
kinase-encoding gene exists. However, nothing is known about its function.
Therefore, we investigated the role of TOR in the GA-producing fungus F.
fujikuroi in order to determine whether TOR plays a role in nitrogen regulation,
especially in the regulation of GA and bikaverin biosynthesis. We cloned and
characterized the F. fujikuroi tor gene. However, we were not able to create
knockout mutants, suggesting that TOR is essential for viability. Inhibition of
TOR by rapamycin affected the expression of AreA-controlled secondary metabolite
genes for GA and bikaverin biosynthesis, as well as genes involved in
transcriptional and translational regulation, ribosome biogenesis, and autophagy.
Deletion of fpr1 encoding the FKBP12-homologue confirmed that the effects of
rapamycin are due to the specific inhibition of TOR. Interestingly, the
expression of most of the TOR target genes has been previously shown to be also
affected in the glutamine synthetase mutant, although in the opposite way. We
demonstrate here for the first time in a filamentous fungus that the TOR kinase
is involved in nitrogen regulation of secondary metabolism and that rapamycin
affects also the expression of genes involved in translation control, ribosome
biogenesis, carbon metabolism, and autophagy.
PMID- 17031004
TI - N-acetylcysteine partially reverses oxidative stress and apoptosis exacerbated by
Mg-deficiency culturing conditions in primary cultures of rat and human
hepatocytes.
AB - OBJECTIVE: The effects of magnesium (Mg) deficiency on the rate of oxidative
stress and apoptosis in primary cultures of human hepatocytes were compared to
cultured rat hepatocytes. The possible reversion by N-acetylcysteine (NAC) in Mg
deficient culturing conditions was evaluated. METHODS: Incubations were conducted
for up to 72 h in media containing a deficient (0-0.4 mM) or a physiological (0.8
mM) Mg concentration, and in the presence or absence of NAC after 24 h of culture
in these Mg concentration conditions. RESULTS: We obtained similar profiles in
terms of apoptosis and oxidative stress in primary cultures of human hepatocytes,
as compared to rat hepatocytes, i.e. a Mg concentration-dependent effect on the
caspase-3 activity and GSH levels after 72 h of culture, caspase-3 activity being
highest and GSH levels being lowest in Mg-free cultures. The addition of NAC to
culture media after the first 24 h of culture increased GSH concentrations. This
was accompanied in Mg-deficient cultures by a decrease in both the caspase-3
activity and the lipid peroxidation. However, when culturing hepatocytes with
physiological Mg concentrations, an increase in both caspase-3 activity and lipid
peroxidation was observed. CONCLUSIONS: Our results indicate that Mg deficiency
exacerbates the rate of apoptosis in cultured hepatocytes, associated with an
increase in oxidative stress, the sensitivity of human hepatocytes being
equivalent to that of rat hepatocytes. They also indicate a dual role of NAC
and/or GSH, i.e. protective for hepatocytes placed in a Mg-deficient environment,
while deleterious for hepatocytes placed in a Mg-physiological environment.
PMID- 17031005
TI - Dietary fiber intake: assessing the degree of agreement between food frequency
questionnaires and 4-day food records.
AB - OBJECTIVE: To assess the degree of agreement (comparability) between dietary
fiber intakes reported on a food frequency questionnaire (FFQ) with 4-day food
records (4DFR) and determine whether demographic, behavioral and biological
factors influence comparability. METHODS: At baseline and year one, all
participants in the Polyp Prevention Trial (PPT), a multi-center randomized,
clinical trial of a low-fat, high fiber, high fruit/vegetable eating plan and
recurrence of large bowel adenomatous polyps were instructed in dietary
assessment and completed a 106-item FFQ and 4DFR that trained nutritionists
reviewed. A random sub-cohort of participants (n = 399) was selected from the
intervention and control arms of the PPT for analysis of both FFQ and 4DFR.
RESULTS: Baseline crude and energy-adjusted fiber intakes were significantly
higher in the 4DFR than the FFQ (P = 0.001). Using Bland-Altman statistics, the
mean difference (FFQ-4DFR) was -0.11 g/MJ; while the limits of agreement were
1.45, 1.23 g/MJ. The mean fiber difference increased with increasing average
intake (FFQ + 4DFR)/2, (P = 0.004) for men, but not women (P = 0.10), suggesting
that fiber intake was under-estimated in the FFQ, relative to the 4-DFR, for men
with low fiber intakes and over-estimated for men with high intakes. Smoking and
gender significantly influenced the average intake at baseline, whereas other
demographic and behavioral factors did not. Education was significantly
associated with average difference in fiber intake at baseline, but not at year
1. CONCLUSIONS: This study of clinical trial volunteers revealed differences in
the ability to comparably report fiber intake across tools by gender, smoking,
and education, however participants' repeated training in dietary assessment
improved comparability in reporting over time.
PMID- 17031006
TI - Food cravings, ethnicity and other factors related to eating out.
AB - OBJECTIVE: Our objective was to study factors related to eating patterns,
specifically whether certain food cravings were associated with frequency of
meals eaten away from home. METHODS: Data were collected from 277 patients from a
family medicine residency office in Arizona. The survey questionnaire included
information about the respondents' demographics, socioeconomic status, food
cravings, as well as, number of meals eaten away from home. The food craving
inventory included foods in four categories identified by factor analysis: fast
foods, carbohydrates, sweets and snacks. Data on food cravings were factor
analyzed and scale scores were derived. RESULTS: Being a Hispanic adult, working
outside the home, and cravings for individual food items were related to eating
more meals away from home. If the mother was working outside the home, the
youngest child ate an average of two additional meals away from home each week.
In general respondent's cravings for some specific food items were also related
to higher numbers of meals their child ate away from home. Cravings for both fast
food and snacks were positively correlated with adult eating out. None of the
respondents' scale scores were related to child's eating away from home. Adults
with Arizona Health Care Cost Containment System insurance (AHCCCS--a form of
Medicaid) and older adults were less likely to eat away from home compared to
patients with other types of insurance. CONCLUSIONS: Socioeconomic status,
ethnicity, and food cravings are related to adult and child patterns of eating
meals away from home.
PMID- 17031007
TI - Evaluating efficacy of a chitosan product using a double-blinded, placebo
controlled protocol.
AB - OBJECTIVE: To examine the safety and efficacy of a chitosan dietary supplement on
body composition under free-living conditions. DESIGN: In a randomized, double
blinded, placebo-controlled dietary intervention protocol, subjects were assigned
to a treatment group (TRT), a placebo group (PLA) and a control group (CTL).
SUBJECTS: A total of 150 overweight adults enrolled; 134 (89.3%) completed the
study; 111 (82.8%) were women who were similarly distributed in the three groups.
INTERVENTION: The TRT group took six 500 mg chitosan capsules per day and both
TRT and PLA groups wore pedometers during their waking hours and recorded daily
step totals. The CTL group followed weight loss programs of their choice, and
took the same baseline and ending tests. MEASURES OF OUTCOME: Outcome measures
were Dual Energy X-ray Absorptiometry tests, fasting blood chemistries, and self
reported daily activity levels and caloric intakes. RESULTS: Compared to CTL, the
TRT group lost more weight (-2.8 lbs vs. +0.8 lbs, p < 0.001) and fat mass (-2.6
lbs vs. +0.1 lbs, p = 0.006). Compared to PLA, the TRT group lost more weight (
2.8 lbs. vs. -0.6 lbs, p = 0.03), % fat (-0.8% vs. +0.4%, p = 0.003), fat mass (
2.6 lbs vs. +0.6 lbs, p = 0.001) and had a greater body composition improvement
index (BCI) (+2.4 lbs vs. -1.9 lbs, p = 0.002). CONCLUSIONS: These data provide
evidence for the efficacy of a chitosan compound to facilitate the depletion of
excess body fat under free-living conditions with minimal loss of fat-free or
lean body mass.
PMID- 17031008
TI - Vitamin D status in a rural postmenopausal female population.
AB - BACKGROUND: Inadequate vitamin D nutritional status is increasingly recognized as
common in North American and European populations, but the extent of the
shortfall and the parameters of the distribution for populations of interest
remain uncertain. PURPOSE: To report the distribution of values for serum 25
hydroxyvitamin D [25(OH)D] in a population of rural postmenopausal women,
together with quantification of factors related to vitamin D status. SETTING:
Nine largely agrarian counties in eastern Nebraska (approximately 41 degrees N).
PARTICIPANTS: A population-based sample of 1,179 women 55 years of age and older
recruited into a four-year trial of calcium and vitamin D supplementation.
METHODS: Baseline biochemical, dietary, and anthropometric measurements obtained
on entry into trial. RESULTS: Serum 25(OH)D concentration at baseline varied
cyclically with season, with the solar cycle explaining 2.9% of the total
variance (P < 0.001). Mean seasonally adjusted 25(OH)D concentration was 71.1
nmol/L. Serum 25(OH)D also exhibited the expected inverse curvilinear
relationship with serum parathyroid hormone (PTH), with the inflection point of
the curve located at approximately 80 nmol/L. Supplements containing vitamin D
were regularly taken by 59% of the cohort (median dose: 200 IU/d). Nevertheless,
approximately 4% of all women had values below the laboratory reference range and
more than two-thirds fell below 80 nmol/L. Seasonally adjusted serum 25(OH)D
concentration was positively correlated with the size of daily vitamin D
supplement dose, and negatively with age, weight, and body mass index (P < 0.01
for all). In stepwise multiple linear regression models, weight, age, and
supplement dose were independently correlated with seasonally adjusted serum
25(OH)D, and together explained 19% of the total variance of adjusted 25(OH)D
concentration. Women taking supplements had only one-sixth the chance of having a
25(OH)D value below the reference limit of the assay, compared to women who did
not use supplements. CONCLUSIONS: Approximately two-thirds of this rural
population fell below 80 nmol/L, a value considered to be the lower end of the
optimal range. Based on the slope of 25(OH)D on supplement dose observed in these
women, it would require an additional vitamin D input of nearly 2000 IU/d to
reach the goal of an RDA for vitamin D, i.e., to bring 97.5% of the cohort to
levels of 80 nmol/L or higher.
PMID- 17031009
TI - Screening performances of the International Obesity Task Force body mass index
cut-off values in adolescents.
AB - OBJECTIVE: To try to improve the International Obesity Task Force (IOTF) BMI cut
off values, in terms of prediction of body fat percentage assessed by dual-energy
X-ray absorptiometry (DXA), in adolescents. METHODS: Cross-sectional survey of
the adolescents from the city of Zaragoza (Spain). For this analysis we have
included 286 adolescents (116 boys and 170 girls) aged 13.0-17.9 years. Body mass
index (BMI) was calculated as body weight (kg), divided by height (m) squared.
The percentage of body fat (BF%) was estimated by the use of DXA. RESULTS: We
have calculated, new BMI cut-off values (AVENA cut-offs) to predict BF%, for boys
and girls in each age group. In male adolescents, sensitivity was higher with the
IOTF cut-offs (0.71, 95th C.I.: 0.44, 0.90) than with the AVENA ones (0.53, 95th
C.I.: 0.28, 0.77), and specificity was very similar with both cut-off values
(0.86 and 0.88, respectively), the differences being not statistically
significant. In girls, both sensitivities (0.75 and 0.79, respectively) and
specificities (0.90 and 0.92, respectively) were very similar with both cut-off
values, and the differences, not significant. CONCLUSIONS: Optimization of the
IOTF BMI cut-off values, in terms of BF%, seems not to be possible in
adolescents. The IOTF criteria should be used only for overweight and obesity
screening; however, in clinical settings, a more accurate measure of body fat
should be recommended.
PMID- 17031010
TI - Effect of a viscous fiber bar on postprandial glycemia in subjects with type 2
diabetes.
AB - OBJECTIVE: To compare the effect of an experimental viscous fiber (VF) crispy bar
on the postprandial glucose, insulin, and C-peptide response in adult subjects
with type 2 diabetes to two commercially available control crispy bars. DESIGN:
The study was a randomized, double-blinded, three period, crossover study.
SETTING: The study was conducted at two sites: Park Nicollet Institute,
International Diabetes Center, Minneapolis, MN, and Radiant Research, Inc.,
Minneapolis, MN. SUBJECTS: A total of 60 adults with type 2 diabetes taking oral
antihyperglycemic medication participated in the study. INTERVENTION: After an
overnight fast, subjects consumed a test meal containing an equicaloric amount
(300 kcal) of an experimental VF crispy bar or one of two commercially available
crispy bars at each of three test visits, followed by a four hour meal tolerance
test. Subjects also completed gastrointestinal (GI) response records for the 24
hours following each test visit. RESULTS: The VF crispy bars produced
significantly lower glucose (p < 0.0001), insulin (p < 0.0001), and C-peptide (p
< 0.0001) responses (as measured by positive area under the curve) in subjects
with type 2 diabetes, as compared with the two commercially available bars.
Intensity (p < 0.05) and frequency (p < 0.05) of flatulence were significantly
higher with the VF bar as compared with the 2 commercial bars. While the VF bar
produced significant subjective GI tolerance scoring values, the mean value was
below 3 on a scale of 0 (no effect) to 10 (most severe effect) for all tested
materials. CONCLUSIONS: The incorporation of VF into a crispy bar provided a
means to improve blood glucose levels by reducing postprandial glucose, insulin,
and C-peptide responses in subjects with type 2 diabetes. Though associated with
some GI symptoms, VF may have application in improving the postprandial glycemic
response in people with diabetes attempting intensive glucose control.
PMID- 17031011
TI - Safety and tolerance of a probiotic formula in early infancy comparing two
probiotic agents: a pilot study.
AB - OBJECTIVE: To compare the safety and tolerance of two formulas, supplemented with
different probiotic agents, in early infancy. DESIGN: Prospective randomized
placebo-controlled trial. SETTING: Clinics of a University Medical Center.
SUBJECTS: Full-term healthy infants aged less than 4 months. INTERVENTION:
Infants were randomly assigned for 4 weeks to a standard milk-based formula
supplemented with either Bifidobacterium lactis (BB-12), Lactobacillus reuteri
(ATCC 55730) or a probiotics-free formula. MEASURES OF OUTCOME: Growth
parameters, daily characteristics of feeding, stooling and behavior, and side
effects. RESULTS: Fifty-nine infants, aged 3-65 days, were included. Subjects in
all three groups were similar at entry in terms of gestational age, birth weight,
sex, growth parameters and breast feeding rate prior to the study. The
supplemented formulas were well accepted and did not reveal any adverse effects.
A comparison of growth parameters, and variables of feeding, stooling and crying
and irritability did not reveal any significant differences between groups.
CONCLUSIONS: The use of formula supplemented with either Lactobacillus reuteri or
Bifidobacterium lactis in early infancy, was safe, well tolerated and did not
adversely affect growth, stooling habits or infant behavior.
PMID- 17031012
TI - Alpha-tocopherol distribution in lipoproteins and anti-inflammatory effects
differ between CHD-patients and healthy subjects.
AB - OBJECTIVE: The purpose of this study was to investigate the dose-dependent
effects of RRR-alpha-tocopherol supplementation in coronary heart disease (CHD)
patients and healthy subjects on plasma alpha-tocopherol levels, plasma
lipoprotein distribution, LDL oxidation, and inflammatory plasma markers.
METHODS: 12 patients with coronary heart disease and 12 healthy subjects were
supplemented with increasing dosages of RRR-alpha-tocopherol at 100, 200 and 400
mg/day for a period of 3 weeks per dose. Lipoproteins were separated by FPLC and
ultracentrifugation. Alpha-tocopherol was measured by HPLC. Resistance of LDL to
oxidation was determined by reading the absorption at 234 nm after CuCl2-induced
oxidation. Clinical chemistry and inflammatory markers were measured on automated
analysis systems. RESULTS: Plasma alpha-tocopherol concentrations at baseline
were comparable between CHD-patients and healthy subjects (21.7 +/- 4.7
micromol/L and 25.8 +/- 7.6 micromol/L, respectively). CHD-patients showed a
significant increase (59%) of plasma alpha-tocopherol concentrations to 34.6 +/-
9.8 micromol/L at a dosage of 100 mg/day RRR-alpha-tocopherol, whereas healthy
subjects showed a significant (54%) increase to 39.7 +/- 6.1 micromol/L only with
400 mg/day RRR-alpha-tocopherol. In addition, CHD-patients showed a significantly
increased enrichment of alpha-tocopherol in VLDL. Supplementation (200 mg/day)
caused a significant decrease of the acute phase plasma proteins C-reactive
protein (CRP) (-65%) and fibrinogen (-24%). CONCLUSION: Our data demonstrate that
CHD-patients require lower dosages of alpha-tocopherol supplementation than
healthy subjects to exert biological effects on plasma lipoproteins and acute
phase response.
PMID- 17031013
TI - How much vitamin D3 do the elderly need?
AB - BACKGROUND: Vitamin D insufficiency poses a problem in many parts of the world,
the elderly being an especially vulnerable group. This insufficiency results from
an inadequate amount of sunshine and a low dietary intake of vitamin D.
Typically, insufficiency is accompanied with high intact parathyroid hormone, (S
iPTH) concentrations. AIMS OF THE STUDY: We studied how serum 25-hydroxy vitamin
D (S-25-OHD) concentrations respond to different doses of vitamin D3
supplementation. Secondly to determine the smallest efficient dose to maintain
serum 25-OHD concentration above the insufficiency level. We also studied which
dose would be efficient in decreasing S-iPTH concentration in these subjects.
SUBJECTS AND METHODS: Forty-nine 65- to 85-year-old women participated. The women
were randomly assigned into one of four groups receiving 0 (placebo), 5, 10 or 20
microg of vitamin D3 daily for 12 weeks. Fasting morning blood was drawn at the
beginning of the study, and thereafter every second week. Calciotropic variables
were assessed from serum and urine samples. RESULTS: The S-25-OHD concentration
increased significantly (p < 0.001) in all supplemented groups [5 microg: by 10.9
(8.5) nmol/L, 10 microg: by 14.4 (6.9) nmol/L, 20 microg: by 23.7 (11.9) nmol/L],
whereas it decreased in the placebo group by 8.3 (13.2) nmol/L. Equilibrium in S
25-OHD concentration was reached in all groups after 6 weeks of supplementation
at 57.7 (8.9) nmol/L, 59.9 (8.9) nmol/L and 70.9 (8.9) nmol/L in the groups with
increasing vitamin D supplementation. The dose-response to supplementation
decreased with increasing vitamin D status at baseline, r = -0.513, p = 0.002. S
iPTH tended to decrease in those with highest dose response to supplementation.
CONCLUSIONS: A clear dose response was noted in S-25-OHD to different doses of
vitamin D3. The recommended dietary intake of 15 microg is adequate to maintain
the S-25-OHD concentration around 40-55 nmol/L during winter, but if the optimal
S-25-OHD is higher than that even higher vitamin D intakes are needed.
Interestingly, subjects with lower vitamin D status at baseline responded more
efficiently to supplementation than those with more adequate status.
PMID- 17031014
TI - Metabolic advantage of low-carbohydrate diets.
PMID- 17031015
TI - Carbohydrate intake, serum lipids, and evolution.
PMID- 17031017
TI - Geographic variation in alcohol, drug, and mental health services utilization:
what are the sources of the variation?
AB - BACKGROUND: Studies have documented geographic variation in health services
utilization over a range of medical, surgical, and psychiatric conditions. These
geographic differences are of concern to policy makers, as they may represent
either excessive levels of unnecessary care or inappropriately low utilization of
necessary services. However, the sources of geographic variation are not well
understood, and variation may not represent a quality problem, to the extent that
geographic variation is due to sampling variability or variation in case-mix
across sites. AIMS OF THE STUDY: Our aim was to determine the extent to which
geographic variation in assessment and treatment rates for alcohol, drug, and
mental disorders (ADM) was due to variation in case-mix across sites and to
quantify the amount of geographic variation after case-mix adjustment. METHODS:
We analyzed data from Healthcare for Communities, a nationally representative
telephone survey of ADM disorders and treatment. We utilized fixed effects and
random intercept models to analyze whether individuals received a brief primary
care ADM assessment, any primary care ADM treatment, any specialty ADM treatment,
or any ADM treatment. Using the coefficient of variation and intra-class
correlation (ICC) as summaries, we simulated reference distributions for the
amount of variability in ADM assessment and treatment rates expected due to
variation in case mix across 60 geographic areas. We compared this with the
actual variation among our 60 sites, and the variation that remained after
adjusting for ADM disorders, physical health, and socioeconomic characteristics.
RESULTS: The amount of the variation in assessment and treatment rates explained
by geographic area in unadjusted fixed effects and random intercepts models was
statistically significant with R2 statistics ranging from 1% to 2% in fixed
effects models and ICC's ranging from 0.009 to 0.043. Considerably more variation
was explained in analyses that included individual level characteristics such as
ADM disorders, physical health, and socioeconomic status, with R2 statistics from
10% to 19%. In random intercept models the ICC's were decreased 20 to 100% in
models that adjusted for ADM disorders, physical health, and socioeconomic
status. DISCUSSION: We found significant variation in ADM assessment and
treatment rates across geographic sites. However, the magnitude of geographic
variation was relatively modest, with 0.9 to 4.3% of the total variation in ADM
assessment and treatment occurring at the geographic level. Further, it appears
that a moderate amount of this geographic variation may be due to differences in
case mix across sites. IMPLICATIONS FOR HEALTH POLICY: Although geographic
variation in assessment and treatment rates can signal variable quality, there
may be only modest potential for improving quality by reducing geographic
variation. Further, the success of efforts to decrease geographic variation by
focusing on provider behavior may be limited by the extent to which systematic
variation is explained by individual characteristics. IMPLICATIONS FOR FURTHER
RESEARCH: Future work on geographic differences in mental health care as well as
in health services more generally should pay particular attention to adjusting
for individual differences in morbidity, which strongly predict treatment
utilization.
PMID- 17031018
TI - Trends in the professional mix and cost of outpatient mental health care.
AB - BACKGROUND: In recent years, lower cost non-physician providers have been
increasingly used to deliver outpatient mental health services. METHODS: We
compared 1997 and 2004 data on outpatient services provided by the Veterans
Health Administration to examine trends in outpatient provider mix and to
evaluate the association of outpatient provider mix with average per capita
outpatient mental health costs. RESULTS: We found a small decline in the
proportion of outpatient mental health services provided by psychiatrists and an
increase in the proportion of such services provided by nurses. However, greater
use of non-physician providers, at the facility level, was associated with
greater, rather than lower per capita outpatient costs and there was no
significant change over time. CONCLUSION: While an increasing proportion of
outpatient mental health visits were with non-psychiatrists, there was not an
associated decline in per capita mental health costs. Increasing VA workloads
over the past decade have forced increases in psychiatrist panel size,
substantially increasing physician efficiency. Additional non-physician staff
have supported the development of psychosocial rehabilitation and crisis
intervention capacities needed to cope with a 63% decline in inpatient beds and
thus have most likely been complements of, rather than substitutes for,
psychiatrists.
PMID- 17031019
TI - A systematic review of relations between neighborhoods and mental health.
AB - BACKGROUND: The relationship between neighborhood characteristics and resident
mental health has been widely investigated in individual studies in recent years,
but this literature is not adequately reviewed. AIMS OF THE STUDY: To
systematically review relevant individual research of the relation between
neighborhoods and adult mental health by identifying and synthesizing all
relevant studies in this literature. METHODS: We conducted an electronic search
with PubMed and PsycINFO, and manual reference-checking, resulting in 8,562
screened studies of which 29 were selected. Studies were included in the main
synthesis if they (i) were published in English in peer reviewed journals; (ii)
had relevant definitions and measures of neighborhood characteristics; (iii)
utilized standardized measures of adult mental health; (iv) controlled for
individual characteristics; (v) reported quantitative results; and, (vi) studied
a population in a developed country. We focused on two key areas within this
literature: the methodologies utilized to study neighborhood effects and
quantitative results. With regard to the former, we examined five major issues:
(i) definitions and measures of neighborhoods; (ii) definitions and measures of
mental health; (iii) controls for individual level characteristics; (iv)
conceptual models; and (v) analytical models. As for quantitative results, the
relation was reviewed by types of neighborhood characteristics. We summarized
general quantitative findings and drew common conclusions across groups of
studies. RESULTS: 27/29 studies found statistically significant association
between mental health and at least one measure of neighborhood characteristics,
after adjusting for individual factors. This association was evident for all
types of neighborhood features, varying from sociodemographic characteristics to
physical environment, and from objective to subjective measures. Neighborhood
effects were weakened when adding individual-level characteristics into the
regression models, and were generally modest relative to individual effects.
DISCUSSION AND LIMITATIONS: Although the evidence is highly consistent across
studies, detailed evaluation of each individual study reveals a complex reality.
The included studies used various study designs and measures of mental health and
neighborhoods, making generalization of their relationships less meaningful. It
is not possible to conclude that studies with weaker controls for individual
characteristics found stronger association between neighborhoods and mental
health and vice versa. As only two studies used randomized and controlled trials,
causal effects must be interpreted with caution. Formal meta-analysis techniques
cannot be used due to large heterogeneity across the included studies. Efficient
methods for quantitative analysis remain a great challenge. IMPLICATIONS FOR
HEALTH POLICY: The current evidence suggests that efforts to improve mental
health may be limited if only individual-level interventions are implemented. The
calculation of the costs and benefits of neighborhood-level interventions
deserves more attention. Moreover, policy makers may want to incorporate mental
health as a measure for evaluating neighborhood improvement programs.
IMPLICATIONS FOR FUTURE RESEARCH: There are not enough replicated or comparable
studies in this literature to make more precise quantitative conclusions of this
relation. Key aspects of study design and analyses could be improved to better
understand the true nature of causal relationships. The data resolution of
neighborhood characteristics needs to better match with the scale of neighborhood
definition that is hypothesized to affect the residents' mental health. As
experimental designs are rare in this area, thoughtful use of panel data,
instrumental variable (IV) techniques, and other non-experimental approaches
deserves further exploration.
PMID- 17031020
TI - Coverage for mental health treatment: do the gaps still persist?
AB - BACKGROUND: Consumers have long faced high out-of-pocket costs for mental health
and substance abuse treatment in private health insurance plans, the predominant
form of insurance coverage in the United States. Nominal mental health benefits
may have improved from the mid-1990s onwards, as many states passed mental health
parity mandates and other employers voluntarily improved coverage. However, the
rapid rise of managed behavioral health care organizations (MBHOs) may have
effectively offset these gains in nominal coverage. AIMS OF THE STUDY: We examine
how effective mental health benefits, as measured by actual out-of-pocket
expenses, compares to coverage for non-mental health treatment and how this has
changed in recent years. METHODS: We used detailed data on health care use and
expenses from the nationally representative, Medical Expenditure Panel Survey
(MEPS) to describe the distribution of out-of-pocket expenses for mental health
and non-mental health ambulatory visits and prescription drug fills and
demonstrate how this changed between 1996 and 2003. In addition, we use two-limit
tobit regression models to descriptively examine the factors associated with
higher out-of-pocket costs for ambulatory mental health treatment. RESULTS: While
out-of-pockets shares generally decreased over the 1996-2003 period, from 39 to
35 percent of total expenses for ambulatory mental health visits and from 31 to
26 percent for non-mental health ambulatory visits, the ratio of out-of-pockets
costs is still significantly higher for mental health care. Out-of-pocket
expenses per visit fell as the number of non-mental health visits increased but
out-of-pocket expenses for mental health visits rose with more visits. Out-of
pocket expenses for visits to specialty mental health providers were
substantially higher than for non-psychiatrist physicians. Though prescription
drug spending increased substantially, the percent paid out-of-pocket did not
change for mental health and non-mental health related fills. DISCUSSION: Our
results suggest that expenses for ambulatory mental health visits, especially for
specialty providers, effectively remain less well covered than other medical
visits. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Continued high out-of
pocket expenses for mental health treatment may impede access to mental health
treatment, especially for those who need greater treatment intensity.
IMPLICATIONS FOR HEALTH POLICIES: Mental health parity may not ensure that
coverage for mental health services is, in actuality, equal. IMPLICATIONS FOR
FURTHER RESEARCH: Additional research is needed in understanding relative changes
in nominal vs. actual or effective coverage.
PMID- 17031021
TI - Application of periodic acid-Schiff fluorescence emission for
immunohistochemistry of living mouse renal glomeruli by an "in vivo
cryotechnique".
AB - To identify the distribution of endogenous serum proteins in living mouse renal
glomeruli under various hemodynamic conditions, we used the periodic acid-Schiff
(PAS) and its fluorescence emission as a marker for the glomerular basement
membrane (GBM). The immunostaining for collagen type IV was hardly observed
without microwave treatment in specimens prepared by an "in vivo cryotechnique".
However, PAS staining and its fluorescence emission could be clearly visualized
at the GBM with the "in vivo cryotechnique". Under normotensive conditions,
immunoreaction products of albumin and immunoglobulin G heavy and light chains
(IgG(H+L)) were localized within glomerular capillary loops (GCL) but not
colocalized with the PAS fluorescence emission of the GBM. Under heart-arrest
conditions and with quick-freezing of resected tissues, albumin, IgG (H+L),
immunoglobulin kappa light chain, and IgG1 heavy chain (IgG1) were
immunolocalized within the GCL and mesangial areas, but only albumin and the
kappa light chain were additionally immunolocalized in Bowman's space, indicating
their passage through the GBM. Under acute hypertensive conditions, both albumin
and the kappa light chain, but not IgG1, were clearly immunolocalized along the
GBM and in the Bowman's space, indicating their increased passage through the
GBM. The overlapping areas of PAS fluorescence emission and the albumin or kappa
light chain appeared to be larger with quick-freezing and under the heart arrest
or acute hypertensive conditions than under normal circulation, whereas those of
PAS emission and IgG1 did not differ among these conditions. The serum proteins
passing through the GBM were clearly visualized with the "in vivo cryotechnique",
immunofluorescence staining, and PAS fluorescence emission.
PMID- 17031022
TI - In vitro adipocytic conversion in Meckel's chondrocytes in response to a fatty
acid-containing medium.
AB - Chick serum (CKS) contains factors that stimulate adipocytes in Meckel's
chondrocytes in vitro. In the present study, we analyzed levels of fatty acids in
CKS, and further examined whether these had the potential to convert chondrocytes
to adipocytes. Phenotypic changes were evaluated by light and electron
microscopies, bromodeoxyuridine (BrdU) incorporation, triglyceride assays, and
immunocytochemistry. We showed that CKS contained high levels of fatty acids, and
a mixed medium containing 5 particular fatty acids inhibited DNA synthesis and
the proliferation of chondrocytes as it facilitated their differentiation into
adipocytes. The adipocytes produced were sudan-positive multilocular cells that
morphologically and histochemically resembled adipocytes induced by the CKS
containing medium. Almost all lipid droplet-containing cells were positive for
leptin and alpha-glycerophosphate dehydrogenase (GPDH), as evaluated by
immunoperoxidase staining, and their triglyceride concentrations markedly
increased during 4 to 6 days of culture. These results suggested that specific
fatty acids in CKS are involved in the adipocytic conversion of Meckel's
chondrocytes.
PMID- 17031023
TI - Sprouting of sensory neurons in dorsal root ganglia after transection of
peripheral nerves.
AB - Morphological reaction of sensory neurons of dorsal root ganglia after peripheral
nerve transection was investigated by a nerve tracing method using E. coli lacZ
(beta-galactosidase) gene recombinant adenovirus. The sciatic nerve of the rat
was transected and inoculated with the gene recombinant adenovirus from the
cutting end of nerve fibers. The fixation was accomplished from one to six weeks
after inoculation. A whole mount specimen was observed after the reaction in a X
galactocidase substrate. Newly formed sprouting processes of dorsal root ganglion
(DRG) cells appeared, all of them sprouting from the primary segment of DRG
cells. Developed branches were morphologically categorized in to two types: one
was the "linear type" which showed diverged branches running straightly along the
major axis of the DRG; the other was the "winding type" which exhibited a random
running pattern to the original axons and wound and extended in all directions in
dorsal root ganglia with many branches. Many of this type encircled other cell
bodies and formed a ring-like structure. There was no difference in the size of
cell bodies in either type or between the ring-like structure forming the cells
and those cells encircled by them.
PMID- 17031024
TI - The expression and localization of osteopontin in the mouse major salivary
glands.
AB - The present study investigated the expression and distribution of osteopontin in
the mouse major salivary glands. The level of osteopontin expression in the mouse
submandibular gland was higher (12.7-fold) than that in parotid and sublingual
glands at the mRNA level. By Western blot analysis, intense positive bands were
seen at the predicted molecular mass (about 55 kDa) in all the major salivary
glands, while an approximately 30 kDa band of osteopontin was detected only in
the submandibular gland. Indirect immunofluorescent and immuno-electron
microscopy analyses demonstrated the localization of osteopontin in the luminal
(apical) membranes of acinar cells in all the salivary glands. Osteopontin was
also localized at the lumen of acini in the submandibular gland. These results
suggest that the expression of osteopontin in the submandibular gland is
different from that in the parotid and sublingual glands and that osteopontin may
be degraded in the mouse submandibular gland.
PMID- 17031025
TI - The bHLH transcription factors, Hes6 and Mash1, are expressed in distinct subsets
of cells within adult mouse taste buds.
AB - Taste buds are multicellular receptor organs embedded in the lingual epithelium
of vertebrates. Taste cells within these buds are modified epithelial cells as
they lack axons and turnover rapidly throughout life, yet have neuronal
properties enabling them to transduce taste stimuli and transmit this information
to the nervous system. Taste cells are heterogeneous, comprising types I, II, III
and basal cells, and are continually replaced during adult life, raising the
question of how these different cells are generated. The molecular mechanisms
governing taste cell differentiation are unknown, but the Notch signaling system
has been implicated in this process based upon recent gene expression data. Here
we investigate the expression in mature taste buds of Notch related transcription
factors, Hes6 and Mash1, which are among the first genes expressed in embryonic
taste buds. We further compare these patterns with those of immunocytochemical
markers of discrete taste cell types. We find that Hes6 is expressed in a subset
of basally located, possibly progenitor cells, yet is rarely coexpressed with
taste cell markers. In contrast, Mash1 is detected in some basal cells and in the
majority of differentiated type III taste cells, but never in type II cells.
These data suggest a role for Notch signaling in taste cell differentiation in
adult taste buds.
PMID- 17031026
TI - High shikimate production from quinate with two enzymatic systems of acetic acid
bacteria.
AB - 3-Dehydroshikimate was formed with a yield of 57-77% from quinate via 3
dehydroquinate by two successive enzyme reactions, quinoprotein quinate
dehydrogenase (QDH) and 3-dehydroquinate dehydratase, in the cytoplasmic
membranes of acetic acid bacteria. 3-Dehydroshikimate was then reduced to
shikimate (SKA) with NADP-dependent SKA dehydrogenase (SKDH) from the same
organism. When SKDH was coupled with NADP-dependent D-glucose dehydrogenase (GDH)
in the presence of excess D-glucose as an NADPH re-generating system, SKDH
continued to produce SKA until 3-dehydroshikimate added initially in the reaction
mixture was completely converted to SKA. Based on the data presented, a strategy
for high SKA production was proposed.
PMID- 17031027
TI - Tumor antigen occurs in N-glycan of royal jelly glycoproteins: honeybee cells
synthesize T-antigen unit in N-glycan moiety.
AB - In our previous paper (Kimura, Y., et al., Biosci. Biotechnol. Biochem., 67, 1852
1856, 2003), we found that a complex type N-glycans containing beta1-3 galactose
residue occurs on royal jelly glycoproteins. During structural analysis of minor
components of royal jelly N-glycans, we found complex type N-glycans bearing both
galactose and N-acetylgalactosamine residues. Detailed structural analysis of
pyridylaminated oligosaccharide revealed that the newly found N-glycan had a
complex type structure harboring a tumor marker (T-antigen) unit: Galbeta1
3GalNAcbeta1-4GlcNAcbeta1-2Manalpha1-6 (Galbeta1-3GalNAcbeta1-4GlcNAcbeta1
2Manalpha1-3) Manbeta1-4GlcNAcbeta1-4GlcNAc. To our knowledge, this may be the
first report of the presence of the T-antigen unit in the N-glycan moiety of
eucaryotic glycoproteins.
PMID- 17031028
TI - Expression profile of amylolytic genes in Aspergillus nidulans.
AB - Aspergillus nidulans possessed 16 putative amylolytic genes consisting of 7 alpha
glucosidase (agdA-F), 7 alpha-amylase (amyA-F), and 2 glucoamylase (glaA and B)
genes on the genome. Among them, the agdA, agdB, agdE, agdF, amyA, amyB, amyF,
and glaB genes were induced by isomaltose. AmyR, a Zn(II)(2)Cys(6) transcription
factor, was required for the induction. The isomaltose-inducible genes possessed
at least one consensus sequence for AmyR binding, 5'-CGGN(8)CGG, on each promoter
region. None of the amylolytic genes was induced by maltose. The mRNA levels of
the amylolytic genes except for agdC, amyD, and amyG increased under carbon
starved conditions. Release from CreA-dependent carbon catabolite repression was
the main cause of the increase, but, the mRNA levels of agdB, agdF, amyB, amyF,
and glaB increased to some extent even in a creA mutant. Therefore, both CreA
dependent and -independent mechanisms are involved in the up-regulation of the
amylolytic genes under carbon-starved conditions.
PMID- 17031029
TI - Sequential regulation of gibberellin, brassinosteroid, and jasmonic acid
biosynthesis occurs in rice coleoptiles to control the transcript levels of anti
microbial thionin genes.
AB - Transcripts of thionin genes encoding antimicrobial peptides were present at a
high level in rice coleoptiles just after germination, and decreased to an
undetectable level after about 3 d, but this decline was suppressed by co
treatment with gibberellic acid (GA(3)) and brassinolide (BL). The temporal
expression patterns of key enzyme genes for the biosyntheses of gibberellins
(GAs) and brassinosteroids (BRs) were correlated with the fluctuation of thionin
mRNAs. Jasmonic acid (JA) replaced the effect of GA3 and BL, and its change in
endogenous level was parallel to that of the thionin genes. These results
strongly suggest that thionin gene expression was positively regulated by JA,
whose endogenous level was synergistically regulated by GAs and BRs. In contrast,
thionin gene expression in etiolated seedlings remained high while the endogenous
level of JA was low, suggesting the presence of another signaling pathway in the
dark to maintain the thionin level.
PMID- 17031030
TI - A novel labdane-type trialdehyde from myoga (Zingiber mioga Roscoe) that potently
inhibits human platelet aggregation and human 5-lipoxygenase.
AB - We screened myoga extracts for inhibitors of human platelet aggregation and human
5-lipoxygenase. We identified a novel labdane type of diterpene, together with
three known diterpenes (miogadial and galanals A and B) from the flower buds of
myoga. Spectroscopic data indicated the structure of the new compound to be 12(E)
labdene-15,16,(8beta)17-trial (miogatrial). Miogatrial and miogadial were potent
inhibitors of human platelet aggregation and human 5-lipoxygenase (5-LOX). The
sesquiterpene, polygodial, also exhibited strong inhibitory activity against
human platelet aggregation and 5-LOX. On the other hand, galanals A and B did not
have inhibitory activity in either experimental system. It thus appears that a 3
formyl-3-butenal structure was essential for the potent inhibition of human
platelet aggregation and human 5-LOX.
PMID- 17031031
TI - Identification of a novel blue pigment as a melanoidin intermediate in the D
xylose-glycine reaction system.
AB - Some blue pigments were formed in the D-xylose (1 M)-glycine (0.1 M) reaction
system. A novel blue pigment, designated as Blue-M2 (blue Maillard intermediate
2), was identified as 5-[1,4-dicarboxymethyl-5-(2,3-dihydroxypropyl)-1,4
dihydropyrrolo[3,2-b]pyrrole-2-ylmethylene]-1,4-dicarboxymethyl-2-{5-[N
carboxymethyl(2,3,4-trihydroxytetrahydrofuran-2-yl)methylamino]-2-hydroxymethyl-4
(1,2,3-trihydroxypropyl)tetrahydrofuran-3-yl}-4,5-dihydropyrrolo-[3,2-b]pyrrole-1
ium. Blue-M2 is presumed to have been generated by the reaction between Blue-M1,
which was identified as the major blue pigment in a previous paper (Hayase et
al., Biosci. Biotechnol. Biochem., 63, 1512-1514 (1999)), and di-D
xyluloseglycine. Blue pigments are important Maillard reaction intermediates
through the formation of melanoidins.
PMID- 17031032
TI - N-linked oligosaccharides of Aspergillus awamori feruloyl esterase are important
for thermostability and catalysis.
AB - A unique N-linked glycosylation motif (Asn(79)-Tyr-Thr) was found in the sequence
of type-A feruloyl esterases from Aspergillus spp. To clarify the function of the
flap, the role of N-linked oligosaccharides located in the flap region on the
biochemical properties of feruloyl esterase (AwFAEA) from Aspergillus awamori
expressed in Pichia pastoris was analyzed by removing the N-linked glycosylation
recognition site by site-directed mutagenesis. N79 was replaced with A or Q. N
glycosylation-free N79A and N79Q mutant enzymes had lower activity than that of
the glycosylated recombinant AwFAEA wild-type enzyme toward alpha
naphthylbutyrate (C4), alpha-naphthylcaprylate (C8), and phenolic acid methyl
esters. Kinetic analysis of the mutant enzymes indicated that the lower catalytic
efficiency was due to a combination of increased Km and decreased k(cat) for
N79A, and to a considerably decreased k(cat) for N79Q. N79A and N79Q mutant
enzymes also exhibited considerably reduced thermostability relative to the wild
type.
PMID- 17031033
TI - Removal of p-alkylphenols from aqueous solutions by combined use of mushroom
tyrosinase and chitosan beads.
AB - Enzymatic removal of p-alkylphenols from aqueous solutions was investigated
through the two-step approach, the quinone conversion of p-alkylphenols with
mushroom tyrosinase (EC 1.14.18.1) and the subsequent adsorption of quinone
derivatives enzymatically generated on chitosan beads at pH 7.0 and 45 degrees C
as the optimum conditions. This technique is quite effective for removal of
various p-alkylphenols from an aqueous solution. The % removal values of 97-100%
were obtained for p-n-alkylphenols with carbon chain lengths of 5 to 9. In
addition, removal of other p-alkylphenols was enhanced by increasing either the
tyrosinase concentration or the amount of added chitosan beads, and their %
removal values reached >93 except for 4-tert-pentylphenol. This technique was
also applicable to remove 4-n-octylphenol (4NOP) and 4-n-nonylphenol (4NNP) as
suspected endocrine disrupting chemicals. The reaction of quinone derivatives
enzymatically generated with the chitosan's amino groups was confirmed by the
appearance of peaks for UV-visible spectrum measurements of the chitosan films
incubated in the p-alkylphenol and tyrosinase mixture solutions. In addition, 4
tert-pentylphenol underwent tyrosinase-catalyzed oxidation in the presence of
hydrogen peroxide.
PMID- 17031034
TI - Amino acid regions of family 45 endoglucanases involved in cotton defibrillation
and in resistance to anionic surfactants and oxidizing agents.
AB - In the detergent industry, fungal endoglucanases are used to release microfibrils
from the surfaces of dyed cellulosic fabrics to enhance color brightness. Family
45 endoglucanase (glycoside hydrolase family 45, GH45) EGL3 from Humicola grisea
is more resistant to anionic surfactants and oxidizing agents than family 45
endoglucanase RCE1 from Rhizopus oryzae, while in the present study, a catalytic
domain of RCE1 had higher defibrillation activity on dyed cotton fabrics than did
that of EGL3. To identify the amino acid regions involved in these properties, we
compared the characteristics of RCE1, EGL3, and three chimeric endoglucanases, in
which each of the three regions of the catalytic domain of EGL3 was replaced by
the corresponding region of the catalytic domain of RCE1. Amino acids in the N
terminal region were involved in resistance to anionic surfactants and oxidizing
agents. Furthermore, amino acids in the region adjacent to the N-terminal region
were involved in releasing microfibrils and in binding to dyed cotton fabrics,
indicating that the binding of the amino acids in this region might be important
in the release of microfibrils from dyed cotton fabrics.
PMID- 17031035
TI - Dietary iron deficiency decreases serum osteocalcin concentration and bone
mineral density in rats.
AB - We investigated the effects of dietary iron deficiency on bone metabolism by
measuring markers of bone turnover in rats. Twelve 3-week-old male Wistar-strain
rats were fed a control diet or an iron-deficient diet for 4 weeks. Dietary iron
deficiency decreased hemoglobin concentration and increased heart weight. Serum
osteocalcin concentration, bone mineral content, bone mineral density, and
mechanical strength of the femur were significantly lower in the iron-deficient
group than in the control group. These results suggested that dietary iron
deficiency affected bone, which might have been due to a decrease in bone
formation in rats.
PMID- 17031036
TI - Utilization study of stems and leaves of Tienchi Ginseng. I. Anti-hypertensive
effect of stems and leaves of Tienchi Ginseng on stroke-prone spontaneously
hypertensive rat (SHRSP).
AB - Tienchi ginseng tea was prepared from stems and leaves of Tienchi ginseng which
is a special product in China. The increase in systolic blood pressure (SBP) was
significantly inhibited by the consumption of a 4% this tea solution as drinking
water from the prehypertensive stage (6 weeks of age) in male stroke-prone
spontaneously hypertensive rats (SHRSP). A similar intake from the hypertensive
stage also showed an anti-hypertensive effect. In contrast, a similar intake had
no effect on SBP of normotensive Wistar Kyoto rats. We found that the rhizome of
Tienchi ginseng contained two types of saponin: 20(s)-protopanaxadiol (PPD) such
as ginsenosides Rb(1) and Rd having a hypotensive effect, and 20(s)
protopanaxatriol (PPT) such as ginsenosides Rg(1) and Re having a hypertensive
effect. In contrast, the tea sample contained PPD and gamma-aminobutyric acid
(GABA), but no PPT. These results suggest that drinking this tea infusion would
be useful for controlling hypertension.
PMID- 17031037
TI - Reduced immunogenicity of beta-lactoglobulin by conjugating with chitosan.
AB - Bovine beta-lactoglobulin (beta-LG) was conjugated with chitosan (CHS) by means
of a water-soluble carbodiimide to reduce the immunogenicity of beta-LG. Each
beta-LG-CHS conjugate was purified by ion-exchange chromatography and hydrophobic
chromatography. The conjugation between beta-LG and CHS was confirmed by SDS
PAGE, the isoelectric point of the conjugate being higher than that of beta-LG.
Two types of the beta-LG-CHS conjugate were obtained with molar ratios of beta-LG
to CHS of 1:1 (F1) and 1:2 (F2). Structural analyses by fluorescence measurement,
ELISA with monoclonal antibodies and retinol-binding activity indicated that the
conjugates had almost maintained the native structure of beta-LG. The
antigenicity of the beta-LG-CHS conjugates was similar to that of beta-LG in
C3H/He mice. Reduction of the immunogenicity of beta-LG was achieved by
conjugation with CHS. In particular, F2 showed very low immunogenicity. B cell
epitopes of beta-LG and the conjugates recognized in C3H/He mice were determined
with 15-mer multi-pin peptide; the linear epitope profiles of the conjugates were
found to be similar to those of beta-LG, while the antibody response to each
epitope was dramatically reduced. Conjugation of beta-LG with chitosan was
effective for reducing the immunogenicity of beta-LG.
PMID- 17031038
TI - Meat tenderizing effect of injecting encapsulated Ca2+ in liposome into rabbit
before slaughter.
AB - Encapsulated calcium in liposome (L-Ca) produced by using egg phosphatidyl
choline in the laboratory was injected into rabbit to evaluate the effect of
calcium injection on the ageing of meat. After injecting L-Ca into the blood
vessels of rabbit to increase the Ca2+ concentration in the body for 24 h, the
fragmentation rate of myofibrils was observed. The fragmentation rates in the
loin from the control group and L-Ca injected group were 2.56% and 3.10% in 2
days, 12.27% and 16.18% in 6 days, and 33.56% and 49.60% in 10 days, respectively
(p<0.05). SDS-PAGE patterns of connectin and nebulin show that the total
degradation of connectin by the control group took longer than 2-3 days, while it
was within 1 day for the L-Ca-injected group. The control group took 8-10 days
for nebulin, while the L-Ca-injected group took 2-3 days for total degradation.
These results indicate that, injecting L-Ca into rabbit was effective for
reducing the ageing period of meat without resulting in any physical shock or
contamination.
PMID- 17031039
TI - Oxygenases and dehalogenases: molecular approaches to efficient degradation of
chlorinated environmental pollutants.
AB - Microbial oxygenases and dehalogenases are key enzymes in the degradation of
highly chlorinated compounds, which often become significant environmental
pollutants. Oxygenases engineered by the methods of directed evolution exhibit
enhanced degradation of PCBs and other chlorinated solvents such as
trichloroethene and pentachloroethane. Dehalorespiration is an efficient
dechlorination mechanism that is coupled with energy-yielding phosphorylation.
Recently, a variety of chloroethene-dehalorespiring anaerobes have been isolated,
and their reductive dehalogenases have been characterized in biochemical and
genetic bases. This review describes our recent studies on dioxygenases and
reductive dehalogenases.
PMID- 17031040
TI - Temperature adaptation of Bacillus subtilis by chromosomal groEL replacement.
AB - We investigated a temperature adaptation of Bacillus subtilis 168 in which
chromosomal groEL was replaced with a psychrophilic groEL. This strain can grow
at 50 degrees C but not at 51 degrees C, a temperature at which wild-type B.
subtilis can grow. Using in vivo random mutagenesis by the B. subtilis mutator
strain (mutS, mutM, mutY), two thermo-adaptants were isolated from the groEL
substituted strain at 52 degrees C. They contained novel amino acid alterations
in their ATP binding motif (T93I) and the inter-monomer contact (R285H) region of
GroEL. These results suggest that GroEL participates in bacterial temperature
adaptation.
PMID- 17031041
TI - Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of
Scutellaria baicalensis GEORGI.
AB - The active ingredients of 'golden root' of Scutellaria baicalensis GEORGI (Huang
Qin), a valuable traditional Chinese medicine, are polyhydroxyflavonoids, namely
baicalein, oroxylin A and wogonin. With the objective of overcoming their poor
solubility and to investigate their structure and activity relationships,
baicaleinyl 7-O-sulfate was prepared, and extensive comparative antioxidative and
anti-inflammatory tests were conducted. All the polyhydroxyflavonoids exhibited
significant antioxidative and free-radical scavenging activities. In respect of
their nitric oxide (NO) inhibition, wogonin was superior to all the other
flavonoids, while oroxylin A was most potent in the inhibition of lipid
peroxidation. Wogonin proved to be the most potent (82.9% inhibition, p<0.05) in
its anti-inflammatory activity against carrageenan-induced rat hind paw edema.
There was a correlation between the in-vivo anti-inflammatory activity and the in
vitro antioxidative activities.
PMID- 17031042
TI - Phenolic constituents of Celosia cristata L. susceptible to spinach root rot
pathogen Aphanomyces cochlioides.
AB - Cochliophilin A (5-hydroxy-6,7-methylenedioxyflavone, 1), known as a host
specific attractant towards the zoospores of Aphanomyces cochlioides, a cause of
root rot and damping-off diseases of Chenopodiaceae, was found in the
Amaranthaceae plant, Celosia cristata, that is susceptible to the pathogen. The
content of 1 in Celosia seedlings was quantified as 1.4 microg/g fresh weight. A
new isoflavone, cristatein (5-hydroxy-6-hydroxymethyl-7,2'-dimethoxyisoflavone,
2), and five known flavonoids were also identified.
PMID- 17031044
TI - Algicidal diterpenes from the brown alga Dictyota dichotoma.
AB - Bioassay-guided fractionation of an ethanol extract of the brown alga, Dictyota
dichotoma, led to the isolation of a novel chlorine-containing perhydroazulene
diterpene together with two known diterpenes, dictyolactone and sanadaol. The
structure of the novel compound, named dictyol J, was elucidated on the basis of
spectroscopic information. Dictyolactone showed the highest algicidal activity
against red-tide phytoplanktons among the three isolated compounds.
PMID- 17031043
TI - Chemoenzymatic synthesis of a MUC1 glycopeptide carrying non-natural sialyl TF
beta O-glycan.
AB - A MUC1 type of glycopeptide was synthesized by the 9-fluorenylmethoxycarbonyl
(Fmoc) solid-phase peptide synthesis (SPPS) protocol using benzyl and benzylidene
protected beta-D-Gal-(1-->3)-beta-D-GalNAc-Ser/Thr (TF-beta: a stereoisomer of
the Thomsen-Friedenreich antigen). The synthetic glycopeptide was released from
the resin with reagent K, and the resulting benzylated glycopeptide was
deprotected under conditions of low-acidity trifluoromethanesulfonic acid (TfOH).
The glycopeptide carrying duplicate non-natural O-glycans was dominant in the
products, but was accompanied by a considerable amount of the glycopeptide
missing one of the O-glycans. In contrast, the native alpha-glycoside was
relatively stable under the acidic debenzylation conditions as shown by a
parallel experiment with the glycopeptide involving alpha-D-GalNAc-Ser/Thr
linkage. Enzymatic glycosylation with CMP-NeuAc was successful with both natural
and non-natural O-glycans of the synthetic glycopeptide.
PMID- 17031045
TI - Royal jelly stimulates bone formation: physiologic and nutrigenomic studies with
mice and cell lines.
AB - Royal jelly (RJ) has diverse physiological and pharmacological functions. We
observed its weak estrogenic activity in the previous study. RJ stimulated the
proliferation of mouse osteoblast-like MC3T3-E1 cells at 0.1 mg/ml, and the
effect was blocked by the specific estrogen receptor antagonist ICI 182,780. The
addition of 0.1-1.0 mg/ml RJ enhanced collagen production in culture medium. Oral
administration of RJ to normal female mice for 9 weeks increased the ash content
of their tibiae. DNA microarray analysis revealed significant changes in gene
expression related to extracellular matrix formation when the femurs of mice fed
RJ were analyzed. Quantitative reverse transcriptase-PCR (RT-PCR) confirmed up
regulation of procollagen I alpha1 gene expression. These data suggest that RJ as
a whole or some of its individual components stimulates production of type I
collagen and other activities for bone formation through action on osteoblasts.
PMID- 17031046
TI - Occurrence of novel nonmethylene-interrupted C24 polyenoic fatty acids in female
gonad lipids of the limpet Cellana grata.
AB - The occurrence of positional isomers of minor C(24) unsaturated fatty acids in
female gonad lipids of the limpet Cellana grata was clarified by gas
chromatography-mass spectrometry of the combination of their 4,4
dimethyloxazoline and picolinyl ester derivatives. In this study, in addition to
5,9-24:2, 9,15-24:2, 5,9,15-24:3, and 5,9,17-24:3, previously identified, 24:4n
6, 24:5n-3, and four novel nonmethylene-interrupted fatty acids, 9,17-24:2,
9,15,18-24:3, 5,9,15,18-24:4, and 5,9,15,18,21-24:5, were newly recognized. All
C(24) unsaturated fatty acids detected were present only in triacylglycerols.
PMID- 17031047
TI - Effects of chlorogenic acid and its metabolites on spontaneous locomotor activity
in mice.
AB - Chlorogenic acid possessed a weak caffeine-like psychostimulant property when
assessed for its effect on spontaneous locomotor activity in mice. In the
evaluation of the effects for the major metabolites of chlorogenic acid which
were detected upon incubation with rat feces and/or excreted in urine after oral
administration to rats, caffeic and m-coumaric acids were found to be the
principal active metabolites, while the others contributed little to this
caffeine-like psychostimulant activity.
PMID- 17031048
TI - Effects of cadmium stress on growth, morphology, and protein expression in
Rhodobacter capsulatus B10.
AB - The effects of cadmium stress on growth, morphology, and protein expression were
investigated in Rhodobacter capsulatus B10 using two-dimensional polyacrylamide
gel electrophoresis and a scanning electron microscope with an energy dispersive
X-ray spectrometer. The bacterium grew in the presence of 150 microM CdCl2 and
highly induced heat-shock proteins (GroEL and Dnak), S-adenosylmethionine
synthetase, ribosomal protein S1, aspartate aminotransferase, and
phosphoglycerate kinase. Interestingly, the ribosomal protein S1 was
proportionally expressed as the amount of cadmium in the medium, suggesting that
S1 may be required for the repair of cadmium-mediated cellular damage. On the
other hand, we identified five cadmium-binding proteins: 2-methylcitrate
dehydratase, phosphate periplasmic binding protein, inosine-5'-monophosphate
dehydrogenase/guanosine-5'-monophosphate reductase, inositol monophosphatase, and
lytic murein transglycosylase. The cadmium-treated cells had a filamentous
structure and contained less phosphorous than the untreated cells. We propose
that these characteristics of the cadmium-treated cells may be due to the
inactivation of the phosphate periplasmic binding protein and lytic murein
transglycosylase by cadmium.
PMID- 17031049
TI - Conversion of capsular polysaccharide, involved in pellicle formation, to
extracellular polysaccharide by galE deletion in Acetobacter tropicalis.
AB - Acetobacter tropicalis SKU1100 produces a pellicle-forming capsular
polysaccharide (CPS), consisting of galactose, glucose, and rhamnose. We cloned
the galE gene, a UDP-galactose synthesis gene, from A. tropicalis SKU1100 by PCR.
A galE-disruptant was prepared and found not to produce CPS and thus not to form
a pellicle under the static condition. Instead, the DeltagalE mutant secreted an
extracellular polysaccharide (EPS), which was purified and found to have a unique
character, different from the original CPS.
PMID- 17031050
TI - Effect of dietary cyclic nigerosylnigerose on intestinal immune functions in
mice.
AB - We examined the dietary effects of cyclic nigerosylnigerose (CNN), a dietary
indigestible oligosaccharide with four D-glucopyranosyl residues linked by
alternating alpha-(1-->3)- and alpha-(1-->6) glucosidic linkages, on the
intestinal immune function of mice, and the effects were compared with those of
alpha-(1-->3)-linked oligosaccharide (nigerooligosaccharides, NOS) or alpha-(1-
>6)-linked oligosaccharide (isomaltooligosaccharides, IMO). BALB/c mice were fed
with 1-5% CNN, 5% IMO, or 12.5% NOS for 4 weeks, and the intestinal mucosal
immune responses were determined. In the 1-5% CNN fed groups, the amounts of IgA
in feces increased significantly. In addition, IgA, transforming growth factor
beta1 (TGF-beta1), and interleukin-6 (IL-6) secretion by Peyer's patch (PP) cells
were enhanced in CNN fed mice. In the 5% CNN group, pH in the cecum decreased,
and the amounts of lactic acid and butyric acid increased. These findings were
not observed in the NOS- or IMO-fed group of mice. They suggest that CNN
supplementation changes the intestinal environment of microflora and indirectly
enhances the immune function in the gut.
PMID- 17031051
TI - Sake yeast suppresses acute alcohol-induced liver injury in mice.
AB - Brewer's and baker's yeasts appear to have components that protect from liver
injury. Whether sake yeast, Saccharomyces cerevisiae Kyokai no. 9, also has a
hepatoprotective effect has not been examined. Here we show that sake yeast
suppresses acute alcoholic liver injury in mice. Male C57BL/6 mice that had been
fed a diet containing 1% sake yeast for two weeks received three doses of ethanol
(5 g/kg BW). In the mice fed sake yeast, ethanol-induced increases in
triglyceride (TG) and glutamate pyruvate transaminase (GPT) were significantly
attenuated and hepatic steatosis was improved. In addition, sake yeast-fed mice
showed a smaller decrease in hepatic S-adenosylmethionine (SAM) level and a
smaller increase in plasma homocysteine (Hcy) level after ethanol treatment than
the control mice, suggesting that a disorder of methionine metabolism in the
liver caused by ethanol was relieved by sake yeast. These results indicate that
sake yeast protects against alcoholic liver injury through maintenance of
methionine metabolism in the liver.
PMID- 17031052
TI - Determination of acylated anthocyanin in human urine after ingesting a purple
fleshed sweet potato beverage with various contents of anthocyanin by LC-ESI
MS/MS.
AB - Eighty-seven healthy volunteers ingested a purple-fleshed sweet potato beverage
with various contents of anthocyanin (beverage A; 22.1 mg/250 ml, B; 107.8, C;
84.9). An acylated anthocyanin, peonidin 3-caffeoylsophoroside-5-glucoside, was
detected in the urine 2 h after ingestion. The concentrations were 15.1+/-2.2
microg/l of urine (mean+/-SEM), 46.6+/-5.3, and 53.3+/-2.2 for beverages A, B,
and C respectively.
PMID- 17031053
TI - Cloning, expression, and characterization of a chitinase from the chitinolytic
bacterium Aeromonas hydrophila strain SUWA-9.
AB - The chitinolytic bacterium Aeromonas hydrophila strain SUWA-9, which was isolated
from freshwater in Lake Suwa (Nagano Prefecture, Japan), produced several kinds
of chitin-degrading enzymes. A gene coding for an endo-type chitinase (chiA) was
isolated from SUWA-9. The chiA ORF encodes a polypeptide of 865 amino acid
residues with a molecular mass of 91.6 kDa. The deduced amino acid sequence
showed high similarity to those of bacterial chitinases classified into family 18
of glycosyl hydrolases. chiA was expressed in Escherichia coli and the
recombinant chitinase (ChiA) was purified and examined. The enzyme hydrolyzed N
acetylchitooligomers from trimer to pentamer and produced monomer and dimer as a
final product. It also reacted toward colloidal chitin and chitosan with a low
degree of deacetylation. When cells of SUWA-9 were grown in the presence of
colloidal chitin, a 60 kDa-truncated form of ChiA that had lost the C-terminal
chitin-binding domain was secreted.
PMID- 17031054
TI - Purification, characterization, and gene analysis of cellulase (Cel8A) from
Lysobacter sp. IB-9374.
AB - An enzyme that has both beta-1,4-glucanase and chitosanase activities was found
in the culture medium of the soil bacterium Lysobacter sp. IB-9374, a high lysyl
endopeptidase-producing strain. The enzyme was purified to homogeneity from the
culture filtrate using five purification steps and designated Cel8A. The purified
Cel8A had a molecular mass of 41 kDa, as estimated by sodium dodecyl sulfate
polyacrylamide gel electrophoresis. A pH optimum of 5.0 was found for the beta
1,4-glucanase activity, and pH optima of 5.0 and 7.0 were found for the
chitosanase activity. Nucleotide sequencing of the Cel8A gene yielded a deduced
amino acid sequence that comprises a 33-amino acid, N-terminal signal peptide and
a mature enzyme consisting of a 381-residue polypeptide with a predicted
molecular mass of 41,241 Da. The amino acid sequence of the Cel8A, which contains
the catalytic module of glycosyl hydrolase family 8, is homologous to beta-1,3
1,4-D-glucanase from Bacillus circulans WL-12 and endoglucanase N-257 from B.
circulans KSM-N257.
PMID- 17031055
TI - Genes encoding small heat shock proteins of the silkworm, Bombyx mori.
AB - Small heat shock protein (sHSP) is a family of ubiquitous polypeptides involved
in a variety of physiological phenomena. From the silkworm, Bombyx mori, we
isolated and sequenced the following cDNAs encoding sHSPs: shsp19.9, shsp20.1,
shsp20.4, shsp20.8, shsp21.4, and shsp23.7. shsp21.4 was nearly twice as large in
size as other shsps. The deduced amino acid sequence of sHSP21.4 was similar to
that of Drosophila melanogaster CG14207-PA. Other sHSPs were highly similar to
each other and, in a phylogenetic tree, formed a cluster including Plodia
interpunctella alphaCP25. It was speculated that shsp21.4 has at least one intron
in genome while other shsps do not. The transcripts of all shsps were subtle, but
were constitutively detected in various tissues. Heat shock triggered a
substantial increase in the transcripts other than shsp21.4. The B. mori sHSPs
are perhaps classified into at least two groups: sHSP21.4 and others.
PMID- 17031056
TI - Stimulatory effects of Pseudosasa japonica leaves on exercise performance.
AB - The performance-enhancing effects of Pseudosasa japonica were investigated in
mice using an adjustable-current water pool. Compared to the control group, a 1.5
fold increase in swimming time was observed in the mouse group administered an
80% ethanol extract (PJE) of the leaves of P. japonica. The blood lactate level,
an important indicator of fatigue, was significantly lower (28%, P<0.05) in PJE
group than in the control group. These results suggest that PJE possesses
stimulatory effects that can enhance exercise endurance and reduce fatigue.
PMID- 17031057
TI - The molecular phylogeny of the genus Rhizopus based on rDNA sequences.
AB - In order to establish the molecular phylogeny of the genus Rhizopus, three
molecules of the ribosomal RNA-encoding DNA (rDNA), complete 18S, internal
transcribed spacer (ITS)1-5.8S-ITS2, and 28S D1/D2 regions of all the species of
the genus were sequenced. Phylogenetic trees showed three major clusters
corresponding to the three groups in the current morphological taxonomy,
microsporus-group, stolonifer-group, and R. oryzae. R. stolonifer var. lyococcos
was clustered independently from the major clusters. R. schipperae clustered
differently in all trees. Strains of R. sexualis had multiple ITS sequences. A.
rouxii clustered with R. oryzae. These results indicate the possibility of
molecular identification of species groups using rDNA sequencing.
Reclassification of the genus might be appropriate.
PMID- 17031058
TI - Identification of Saccharomyces cerevisiae ribosomal protein L3 as a target of
curvularol, a G1-specific inhibitor of mammalian cells.
AB - The cellular target of curvularol, a G1-specific cell-cycle inhibitor of
mammalian cells, was identified by a genetic approach in Saccharomyces
cerevisiae. Since the wild-type W303 strain was highly resistant to curvularol, a
drug hypersensitive parental strain was constructed in which various genes
implicated in general drug resistance had been disrupted. Curvularol resistant
mutants were isolated, and strains that exhibited a semi-dominant, curvularol
specific resistance phenotype were selected. All five strains examined were
classified into a single genetic complementation group designated YCR1. A mutant
gene responsible for curvularol resistance was identified as an allele of the
RPL3 gene encoding the ribosomal protein L3. Sequence analysis of the mutant
genes revealed that Trp255Cys and Trp255Leu substitutions of Rpl3p are
responsible for curvularol resistance. Rpl3p mutants in which Trp255 residue was
replaced by other amino acids were constructed. All of these replacements led to
varying degrees of increased resistance to curvularol and growth defects.
PMID- 17031059
TI - Antihyperglycemic activity of herb extracts on streptozotocin-induced diabetic
rats.
AB - We investigated the effects of herb extracts, Rhus verniciflua, Agrimonia pilosa,
Sophora japonica, and Paeonia suffruticosa, on the lowering of blood glucose
levels and thiobarbituric acid reactive substances (TBARS) in streptozotocin
(STZ)-induced diabetic rats. After 4 weeks, oral administration of Rhus
verniciflua extract (50 mg/kg) exhibited a significant decrease in blood glucose
levels in diabetic rats (P<0.05). Blood TBARS concentrations, the products of
glucose oxidation in blood, were also lowered by Rhus verniciflua extract
supplementation. In addition, Sophora japonica and Paeonia suffruticosa extracts
significantly reduced TBARS levels versus diabetic controls. Serum concentrations
of liver-function marker enzymes, GOT and GPT, were also restored by Rhus
verniciflua (50 mg/kg) supplementation in diabetic rats.
PMID- 17031060
TI - Enantioselective synthesis of the (1S,5R)-enantiomer of litseaverticillols A and
B.
AB - An enantioselective synthesis of the (1S,5R)-enantiomer of litseaverticillols A
and B was accomplished in line with our previously reported synthetic pathway for
their (1R,5S)-enantiomer. The use of "EtSCeCl2" prepared from EtSLi and CeCl3,
instead of previously employed EtSLi itself, for the formation of thiol ester
intermediates prevented any undesirable epimerization occurring in the process.
PMID- 17031061
TI - Suppression of methionine-induced hyperhomocysteinemia by glycine and serine in
rats.
AB - The hyperhomocysteinemia induced by a dietary addition of 1% methionine was
significantly suppressed by the concurrent addition of 1% glycine or 1.4% serine
to the same degree. The methionine-induced increase in the hepatic concentration
of methionine metabolites was significantly suppressed by glycine and serine, but
the hepatic cystathionine beta-synthase activity was not enhanced by these amino
acids. When the methionine-supplemented diet was changed to the methionine plus
glycine or serine diet, the plasma homocysteine concentration rapidly decreased
during and after the first day. The hyperhomocysteinemia induced by an
intraperitoneal injection with methionine was also suppressed by concurrent
injection with glycine or serine, although the effect of serine was significantly
greater than that of glycine. These results indicate that glycine and serine were
effective for suppressing methionine-induced hyperhomocysteinemia: serine and its
precursor glycine are considered to have elicited their effects mainly by
stimulating cystathionine synthesis by supplying serine, another substrate for
cystathionine synthesis.
PMID- 17031062
TI - Synthesis of gerfelin and related analogous compounds.
AB - Gerfelin, an inhibitor of human geranylgeranyl diphosphate (GGPP) synthase that
has been isolated from a culture broth of Beauveria felina QN22047, was
synthesized in 4 and 3 steps starting from 2,4-dihydroxy-6-methylbenzoic acid and
3,4,5-trihydroxytoluene, respectively. An effective ligand, 2-(di-tert
butylphosphino)biphenyl, was used in the palladium-catalyzed diaryl ether-forming
reaction. Five analogous compounds of gerfelin were also synthesized for a study
of the structure-activity relationship.
PMID- 17031063
TI - Antioxidants in fruits and vegetables: a study of cellular availability and
direct effects on human DNA.
AB - The effects of several types of whole fruits and vegetables on human lymphocytic
DNA were investigated by using two versions of the comet assay. The total
antioxidative capacity, as the FRAP value, and ascorbic acid (AA) content were
also measured to explore the relationship between the effect and antioxidant
content.
PMID- 17031064
TI - Partial replacement of waxy cornstarch by recrystallized amylose retards the
development of insulin resistance in rats.
AB - We examined in rats whether or not the prolonged ingestion of recrystallized
amylose (RCA) would prevent the development of insulin resistance. Rats were fed
on a diet containing waxy cornstarch (WCS) as carbohydrate or a diet containing
30% RCA in place of WCS for 18 wk. Glucose tolerance test (GTT) was conducted at
every four weeks. On wk 16, the plasma insulin response as assessed by the area
under the curve was lower in the RCA diet group than in the WCS diet group. The
fasting plasma insulin level tended to increase over time in both groups, but was
lower in the RCA diet group on wk 16. An autopsy revealed that the adipose tissue
mass and serum free fatty acid concentrations were significantly higher in the
WCS diet group. The results suggest that prolonged ingestion of RCA had the
effect of slowing the development of insulin resistance through a lower
concentration of serum free fatty acids, presumably due to the prevention of
adipocyte hypertrophy.
PMID- 17031065
TI - Determination of the absolute configuration of quercivorol, (1S,4R)-p-menth-2-en
1-ol, an aggregation pheromone of the ambrosia beetle Platypus quercivorus
(Coleoptera: Platypodidae).
AB - A pair of enantiomers of trans-p-menth-2-en-1-ol, an aggregation pheromone of
Platypus quercivorus, was synthesized from (S)- and (R)-limonene. The retention
time of the aggregation pheromone from the insect coincided with that of (1S,4R)
p-menth-2-en-1-ol synthesized from (S)-limonene from GC analyses with a chiral
column, enabling the absolute configuration of the aggregation pheromone to be
determined as (1S,4R).
PMID- 17031066
TI - Azelnidipine down-regulates renal angiotensin-converting enzyme and
mineralocorticoid receptor mRNA in diabetic hypertensive rats.
AB - Effects of a new lipophilic L-type calcium channel blocker, azelnidipine, on the
expression of molecular components of the renin-angiotensin-aldosterone system
(RAAS) were assessed. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a
model of diabetes with hypertension, and their lean littermates, Long-Evans
Tokushima Otsuka (LETO) rats, were treated with azelnidipine for 2 weeks. The
renal cortical mineralocorticoid receptor mRNA in OLETF was higher than in LETO,
but was suppressed (P<0.05) by azelnidipine. Renal cortical angiotensin
converting enzyme mRNA of OLETF was lower than that of LETO rats, and it was
further suppressed by azelnidipine (P<0.05). Azelnidipine can down-regulate the
gene expression of molecular components of RAAS.
PMID- 17031067
TI - Increase in expression of alpha1 and alpha2/delta1 subunits of L-type high
voltage-gated calcium channels after sustained ethanol exposure in cerebral
cortical neurons.
AB - Previous reports revealed up-regulation of L-type high voltage-gated calcium
channels (HVCCs) in mouse brains with ethanol physical dependence. We
investigated mechanisms of enhancement of L-type HVCC function using mouse
cerebrocortical neurons exposed to 50 mM ethanol for 3 days and the brains of
mouse physically dependent on ethanol. Ethanol facilitated 30 mM KCl-stimulated
(45)Ca(2+) influx in dose- and duration-dependent manners, which was abolished by
nifedipine, an inhibitor specific to L-type HVCCs, but not by inhibitors for
other types of HVCCs. Increase in [(3)H]PN200-110 binding to the particulate
fractions from the ethanol-treated neurons was due to increased B(max) value with
no changes in K(d) value. Western blot analysis showed the increased expression
of alpha1C, alpha1D, and alpha2/delta1 subunits with decreased beta4 subunit
expression and no changes in expressions of alpha1A, alpha1B, alpha1F, and alpha2
subunits. A similar pattern of the changes in the expression of these subunits of
L-type HVCCs were observed in the cerebral cortex from mouse with ethanol
physical dependence. These results indicate that sustained ethanol exposure to
the neurons induces up-regulation of L-type HVCCs, which is due to increased
expressions of alpha1C, alpha1D, and alpha2/delta1 subunits, and produces no
alterations in P/Q- and N-type HVCC functions.
PMID- 17031068
TI - The elucidation of the mechanism of weight gain and glucose tolerance
abnormalities induced by chlorpromazine.
AB - Antipsychotic drugs induce weight gain and metabolic abnormalities. Recently, the
role of adipocytokines secreted from adipocytes in the development of metabolic
syndrome has received attention. The aim of this study was to investigate the
effects of chlorpromazine (Cp) on body weight, glucose, lipid metabolism, and
adipocytokine secretion in rats fed sucrose. Wistar rats received 15% sucrose
(Suc group), 15% sucrose and Cp at 7.5 mg/kg per day (Suc + Cp group), or Cp
alone (Cp group) in water for 10 weeks. Fasting glucose levels in the Suc and Suc
+ Cp groups were significantly higher than in the control (Cont) group. Fasting
insulin levels in the Suc, Suc + Cp, and Cp groups were also significantly higher
than in the Cont group. The adiponectin level in the Suc group was significantly
higher than in the Cont group, although the adiponectin level in the Suc + Cp
group was not. Furthermore, the plasma tumor necrosis factor (TNF)-alpha level in
the Suc + Cp group was significantly higher than in the Suc group. These data
suggest that Cp inhibits the compensatory response of adiponectin with respect to
obesity due to increased expression of plasma TNF-alpha level. Cp may exert more
harmful effects on the glucose level and insulin resistance than on other
factors, which may be one of the mechanisms responsible for the metabolic
syndrome induced by antipsychotic agents.
PMID- 17031069
TI - Pharmacological profiles of the novel analgesic M58996 in rat models of
persistent and neuropathic pain.
AB - We investigated the effects of 4-(N-{1-[2-(4-cyanophenyl)ethyl]-4
hydroxypiperidin-4-ylmethyl}-N-methylamino)benzoic acid monohydrochloride
(M58996), a novel analgesic, on persistent and neuropathic pain in rats. In the
formalin test, oral M58996 (0.3 - 10 mg/kg) reduced nociceptive behaviors only in
the late phase. In the neuropathic pain model, oral M58996 (1 - 10 mg/kg)
attenuated mechanical allodynia and heat hyperalgesia in the nerve-injured paw
without affecting normal responses of the uninjured paw. High doses (10 - 100
mg/kg) of oral M58996 did not influence normal motor function. Thus, M58996 had a
wide dose range showing antinociceptive, antiallodynic, and antihyperalgesic
effects without motor dysfunction. In addition, we studied the possible
mechanisms involved in the M58996-induced antinociception. The antinociceptive
effect of M58996 was reversed by intrathecal pertussis toxin, an inhibitor of the
inhibitory- and other-GTP-binding protein (G(i/o) protein), but not by
subcutaneous naloxone, an opioid-receptor antagonist. This effect was also
reversed by intracerebroventricular or intrathecal tropisetron, a 5
hydroxytryptamine(3) (5-HT(3))-receptor antagonist, and intraperitoneal
bicuculline, a gamma-aminobutyric acid(A) (GABA(A))-receptor antagonist. These
results suggest that M58996 produces its antinociceptive effect by a pertussis
toxin-sensitive G protein mechanism. In addition, the GABA released by the
activation of supraspinal and/or spinal 5-HT(3) receptors is likely to contribute
to the M58996-induced antinociception.
PMID- 17031070
TI - Lig-8, a bioactive lignophenol derivative from bamboo lignin, protects against
neuronal damage in vitro and in vivo.
AB - Lig-8, a lignophenol derivative from bamboo lignin, potently suppresses oxidative
stress-induced apoptosis. Here, we first examined in vitro whether lig-8 protects
against neuronal damage induced by oxygen-glucose deprivation (OGD) followed by
reoxygenation, tunicamycin [endoplasmic reticulum (ER)-stress inducer], or PSI
(proteasome inhibitor). In pheochromocytoma (PC12) cell cultures, lig-8 (1 to 30
microM) concentration-dependently inhibited OGD- and tunicamycin (2 microg/ml)
induced cell deaths (significant at >/=3 microM and >/=1 microM, respectively).
In human neuroblastoma (SH-SY5Y) cell culture, the PSI-induced apoptotic cell
death and fusion protein accumulation (revealing reduced proteasome activity) was
inhibited by lig-8 (30 microM). On the other hand, lig-8 at 30 microM alone did
not affect any proteasome activity under resting conditions. In vivo, lig-8 (0.1
nmol/eye) reduced intravitreal N-methyl-D-aspartate (NMDA, 20 nmol)-induced
retinal damage (decreases in retinal ganglion cells and inner plexiform layer
thickness). Hence, lig-8 protects, partly by inhibiting excessive ER-stress,
against neuronal damage in vitro and in vivo.
PMID- 17031071
TI - Inverse agonist activity of sarpogrelate, a selective 5-HT2A-receptor antagonist,
at the constitutively active human 5-HT2A receptor.
AB - Mutations producing constitutively active G-protein coupled receptors have been
found in the pathophysiology of several diseases, implying that inverse agonists
at the constitutively active receptors may have preferred therapeutic
applications. Because of the involvement of 5-HT(2A) receptors in mediating many
cardiovascular diseases, constitutively active mutants of the 5-HT(2A) receptor
may be responsible for the disease states. Thus, the purpose of the present study
was to investigate the inverse agonist activity of sarpogrelate, a selective 5
HT(2A)-receptor antagonist, and its active metabolite, M-1; and we compared their
activities with those of other 5-HT(2A)-receptor antagonists such as ritanserin,
ketanserin, and cyproheptadine. Using a constitutively active mutant (C322K) of
the human 5-HT(2A) receptor, we demonstrated that like other 5-HT(2A)-receptor
antagonists, sarpogrelate acts as a potent inverse agonist by significantly
reducing basal inositol phosphate levels. However, there were no significant
differences between sarpogrelate and other 5-HT(2A)-receptor antagonists for
their inverse agonist activity. Compared with the wild type receptor, mutant
receptor displayed significantly higher affinity for 5-HT and lower affinity for
sarpogrelate. These results indicate that stabilization of the inactive
conformation of the 5-HT(2A) receptor may be a key component of the mechanism of
action of sarpogrelate.
PMID- 17031072
TI - Protective effect of prostaglandin EP4-receptor agonist on anti-glomerular
basement membrane antibody-associated nephritis.
AB - Prostaglandin E(2)-receptor subtypes, EP(1), EP(2), EP(3), and EP(4), are present
in the kidney. The aim of this study was to elucidate the anti-nephritic effect
of an EP(4)-receptor agonist on an experimental nephritic model. Mice were
injected i.v. with anti-glomerulus antiserum to induce nephritis. Nephritic
glomeruli generated more prostaglandin E(2) (2.6 and 0.7 ng) and less cyclic AMP
than normal glomeruli (11 and 26 pmol). The production of cyclic AMP in nephritic
glomeruli increased 67% in response to AE1-329, an EP(4) agonist, at 10(-5) M.
Nephritic glomeruli expressed a lesser amount of mRNA of prostaglandin E(2)
receptor subtypes as compared with normal glomeruli. AE1-329 was administered
s.c. at 100 microg/kg per day for 3 weeks. AE1-329 suppressed the increase in
creatinine and cholesterol compared to those in the control nephritic mice. AE1
329-treated nephritic mice had less crescentic glomeruli and less deposition of
rabbit IgG (anti-glomerular basement membrane antibody) in glomeruli than the
control mice. AE1-329 prevented the development of glomerulonephritis. These
findings suggest that EP(4)-receptor agonists are a promising drug to prevent the
development of glomerulonephritis.
PMID- 17031073
TI - Insufficient expression of cyclooxygenase-2 protein is associated with retarded
degradation of aggregated protein in diabetic glomeruli.
AB - To elucidate the involvement of cyclooxygenase (COX) in degradation of aggregated
protein in diabetic glomeruli, we used streptozotocin (STZ)-induced diabetic mice
and aggregated bovine serum albumin (a-BSA) as a model protein. There was a
higher deposition of a-BSA in diabetic glomeruli compared to normal glomeruli 18
h after a-BSA injection at 4 and 8 weeks after STZ. Degradation of a-BSA was
confirmed using isolated glomeruli. Diabetic glomeruli produced prostaglandin
E(2) (PGE(2)) more than normal glomeruli in the basal level at 8 weeks. a-BSA
caused further increase of PGE(2) production in normal glomeruli, but not in
diabetic glomeruli. Niflimic acid, a selective COX-2 inhibitor, reduced PGE(2)
production of normal glomeruli in the a-BSA loading group, but not that in the
control group. In diabetic glomeruli, niflimic acid reduced PGE(2) production in
both the control group and a-BSA loading group. In normal glomeruli, a-BSA
increased expressions of both COX-2 mRNA and protein. However, in diabetic
glomeruli, a-BSA increased COX-2 mRNA expression but not COX-2 protein
expression. These results suggest that retarded degradation of aggregated protein
in diabetic glomeruli is associated with lack of further expression of COX-2
protein and further production of PGE(2) in response to aggregated protein.
PMID- 17031074
TI - Beta-blockers show inverse agonism to a novel constitutively active mutant of
beta1-adrenoceptor.
AB - We obtained a new mutant of the beta(1)-adrenergic receptor (beta(1)-AR) by point
mutations that can constitutively activate beta(1)-AR. Aspartate104 of the
beta(1)-AR in the 2nd transmembrane was replaced with alanine. The beta(1)-AR
mutant expressed in human embryonic kidney (HEK)-293 cells displayed high level
of constitutive activity with respect to wild-type (P<0.05), which could be
partially inhibited by some beta-blockers. The constitutive activity of the
mutant was confirmed by the finding that the enhanced activity is dependent on
the level of receptor expression. The results of this study might have
interesting implications for future studies aiming at elucidating the activation
process of the beta(1)-AR as well as the mechanism of action of beta-blockers.
PMID- 17031075
TI - Signaling pathways involved in the cardioprotective effects of cannabinoids.
AB - The aim of the present article is to review the cardioprotective properties of
cannabinoids, with an emphasis on the signaling pathways involved. Cannabinoids
have been reported to protect against ischemia in rat isolated hearts, as well as
in rats and mice in vivo. Although these effects have been observed mostly with a
pre-treatment of a cannabinoid, we report that the selective CB(2)-receptor
agonist JWH133 is able to reduce infarct size when administered either before
ischemia, during the entire ischemic period, or just upon reperfusion. Little is
known about the signaling pathways involved in these cardioprotective effects.
Likely candidates include protein kinase C (PKC) and mitogen-activated protein
kinases (MAPK) since they are activated during ischemia-reperfusion and
contribute to the protective effect ischemic preconditioning. The use of
pharmacological inhibitors suggests that PKC, p38 MAPK, and p42/p44 MAPK (ERK1/2)
contribute to the protective effect of cannabinoids. In addition, perfusion with
JWH133 in healthy hearts caused an increase in both p38 MAPK phosphorylation
level and activity, whereas the CB(1)-receptor agonist ACEA was associated with
an increase in the phosphorylation status of both ERK1 and ERK2 without any
change in activity. During ischemia, both agonists doubled p38 MAPK activity,
whereas ERK1/2 phosphorylation level and activity during reperfusion were
enhanced only by the CB(1)-receptor agonist. Finally, although nitric oxide (NO)
was shown to exert both pro and anti-apoptotic effects on cardiomyocytes, with an
apparently controversial effect on myocardial survival, our data suggest that NO
may contribute to the cardioprotective effect of some cannabinoids.
PMID- 17031077
TI - Difficult-airway management need not be difficult!
PMID- 17031076
TI - Development of genetically engineered mice lacking all three nitric oxide
synthases.
AB - Nitric oxide (NO) is produced in almost all tissues and organs, exerting multiple
biological actions under both physiological and pathological conditions. NO is
synthesized by three different isoforms of NO synthase (NOS): neuronal,
inducible, and endothelial NOSs. Due to the substantial compensatory interactions
among the NOS isoforms, the ultimate roles of endogenous NO in our body still
remain to be fully elucidated. To address this point, we have successfully
developed mice in which all three NOS genes are completely disrupted. NOS
expression and activities were totally absent in the triply n/i/eNOS(-/-) mice
before and after treatment with lipopolysaccharide. While the triply n/i/eNOS(-/
) mice were viable, their survival and fertility rates were markedly reduced as
compared with wild-type mice. The phenotypes of those mice that we first noticed
were polyuria, polydipsia, and renal unresponsiveness to vasopressin,
characteristics consistent with nephrogenic diabetes insipidus. We subsequently
observed that in those mice, arteriosclerosis is spontaneously developed with a
clustering of cardiovascular risk factors. These results provide the first
evidence that the systemic deletion of all three NOSs causes a variety of
cardiovascular diseases in mice, demonstrating a critical role of the endogenous
NOSs system in maintaining cardiovascular homeostasis.
PMID- 17031078
TI - Unanticipated difficult intubation.
AB - PURPOSE OF REVIEW: While there are many predictors of difficult laryngoscopic
intubation, they all have a low positive predictive value. Therefore,
unanticipated difficult laryngoscopic intubation will likely occur in our day-to
day practice. This review discusses recent developments in alternative airway
devices and techniques in addressing these difficulties. RECENT FINDINGS: There
is emerging evidence to suggest that new supraglottic devices are useful rescue
appliances, particularly for unanticipated difficulties in laryngoscopic
intubation. Other new intubating devices, including the Glidescope, may also play
an important role in the management of patients with unanticipated difficult or
failed laryngoscopic intubation. SUMMARY: The evidence to date does not always
arm us with the ability to predict a difficult laryngoscopic intubation.
Therefore, it is imperative that we equip ourselves with devices and techniques
that will help us to maintain effective oxygenation and ventilation in a safe
manner in the face of such failure.
PMID- 17031079
TI - Algorithms for management of the difficult airway.
AB - PURPOSE OF REVIEW: The purpose of this review is to examine recent evidence for
the management of the difficult airway. RECENT FINDINGS: Recent findings still
recommend the importance of a predefined, simple strategy for both the
anticipated and unanticipated difficult airway. For the former, awake fiberoptic
intubation is still the 'gold standard'. For management of the unanticipated
difficult airway, the use of the laryngeal mask airway (LMA), intubating
laryngeal mask airway (ILMA), the 'gum elastic bougie' and fiber-optics are
recommended. If intubation and ventilation fails, cannula or surgical
cricothyroidotomy should be an early consideration. SUMMARY: This review of
algorithms for management of the difficult airway strengthens several generally
accepted crucial points. What is always needed is expertise, which one can only
get and maintain by daily practice.
PMID- 17031080
TI - Trends in tracheal intubation: emphasis on the difficult airway.
AB - PURPOSE OF REVIEW: This review will summarize the progress made during the last
year in improving difficult-airway management. RECENT FINDINGS: The UK Difficult
Airway Society have published extensive guidelines for the management of
unanticipated difficult intubation in the unobstructed adult patient. That such
an approach is useful has been demonstrated in an independent study which showed
that simple guidelines using familiar equipment will solve the majority of
intubation difficulties likely to be encountered. However, their limitation lies
in the fact that the worst-case scenario (i.e. inability to ventilate or
intubate) is so rare that it cannot be studied systematically. It is postulated
that a different approach geared to understanding the causes of difficulties with
intubation may provide an alternative strategy for providing an evidence base.
SUMMARY: Significant steps have been made in our management of the difficult
airway, and the majority of the problems encountered can be solved with recourse
to simple published guidelines.
PMID- 17031081
TI - Recent trends in tracheal intubation: emphasis on the difficult airway.
AB - PURPOSE OF REVIEW: Difficult airways can lead to critical incidents during
anaesthesia, and death. Although many cases can be anticipated, some still go
undiscovered before induction, thereby exposing the patient to unexpected risks
and the anaesthesiologist to unexpected challenges. In addition to improving
prediction of difficult airways, education for skill acquisition and management
planning, and a quest for superior management techniques and airway tools are of
the utmost importance in preventing airway catastrophes. RECENT FINDINGS: We
review recent advances in predicting difficult airways in special population
groups that are known to have a higher incidence of difficult airway. Education,
exercising airway skills, management planning with both predicted and unpredicted
difficult airways, and the need for adherence to algorithms for management of
difficult airway are emphasized as key to successful management. Finally, recent
developments in airway management techniques and new airway devices are
summarized. SUMMARY: Improving reproducibility and reliability in predicting a
difficult airway may limit the number of unpredicted difficult intubations. A
safer approach to management of the difficult airway can be achieved by improving
airway management skills and adhering to universally accepted and proven airway
algorithms, including developing approaches to management of predicted and
unpredicted difficult airways. Improving on existing airway techniques and tools
(of which there are many), rather than creating new devices, is a desirable trend
that may contribute to safer airway management in the future.
PMID- 17031082
TI - Laryngeal mask airway and the difficult airway.
AB - PURPOSE OF REVIEW: To present recent advances in the role of the laryngeal mask
airway (LMA) and its newer modifications in the management of difficult airway.
RECENT FINDINGS: The principles of management of a difficult airway remain the
same, but the advent of the intubating LMA (ILMA) and Proseal LMA (PLMA) has
provided a better choice in such situations. While fiberoptic intubation remains
the preferred choice of many anaesthesiologists, the ILMA provides equal or
better conditions for intubation when compared with the awake technique. The PLMA
with its better safety profile is proving valuable in the emergency scenario.
SUMMARY: ILMA and PLMA have been shown to be effective in the management of
difficult airway. We recommend that training in the use of these devices be made
mandatory.
PMID- 17031083
TI - Alternative management techniques for the difficult airway: optical stylets.
AB - PURPOSE OF REVIEW: We present the newest devices being promoted for difficult
airway management. Our focus is on optical stylets which offer a forward view
from the stylet end positioned within the tip of the endotracheal tube. RECENT
FINDINGS: Reports suggest that these devices are mastered quickly and offer
effective airway management aid. Available in adult and pediatric sizes they are
economically priced at approximately US$ 3000. SUMMARY: Generally favorable
experience with use of optical stylets continues to be reported. Our survey of
clinicians' opinions reflects our own experience; these devices are unique and
are attractive adjuncts to standard- and difficult-airway carts.
PMID- 17031084
TI - Alternative management techniques for the difficult airway: esophageal-tracheal
Combitube.
AB - PURPOSE OF REVIEW: To summarize knowledge about the esophageal-tracheal Combitube
in emergency medicine and anesthesia, with special emphasis on uncommon
indications. Papers published between August 2003 and July 2004 are reviewed.
RECENT FINDINGS: Tracheal intubation in the field is difficult and success rates
are dependent upon training level (90-98%). Therefore, the esophageal-tracheal
Combitube has been recommended for emergency ventilation after failed tracheal
intubation with success rates of about 90%, even when performed by emergency
medical technicians. Combitube insertion is easy to learn, but practice is
necessary to retain skills. Use of this device has also been recommended for
ventilatory support during routine anesthesia. Combitube ventilation is
successful in over 96% of patients, with minimal trauma. Since only a small
percentage of American anesthesiologists are familiar with the Combitube (<50%),
using the device in anesthesia care may improve the skills required during
emergency airway management. Blood gases are in the range of those obtained
during endotracheal tube ventilation and aspiration prophylaxis is at least as
good as that of the laryngeal mask airway. Successful uncommon uses of the device
have also been recommended, for example, Combitube ventilation in
craniomaxillomandibular surgery via the submental route and insertion of the
device in a burns patient with minimal mouth opening and significant tracheal
stenosis after long-term ventilation. SUMMARY: The esophageal-tracheal Combitube
is a useful and efficient alternative airway characterized by high success rates
in emergency situations. We recommend the use of a laryngoscope for insertion and
strict adherence to the manufacturer's guidelines in order to maximize success
and minimize potential injury.
PMID- 17031085
TI - The Williams Airway Intubator, the Ovassapian Airway and the Berman Airway as
upper airway conduits for fibreoptic bronchoscopy in patients with difficult
airways.
AB - PURPOSE OF REVIEW: In this article we will summarize the available information on
airways that have been suggested to provide a conduit for the bronchoscope in its
passage through the upper airway during fibreoptic intubation. RECENT FINDINGS:
The Williams Airway Intubator and the Berman Oropharyngeal Airway appear to be
more likely to provide a conduit for the bronchoscope than the Ovassapian
Fibreoptic Intubating Airway. SUMMARY: Though the Williams Airway Intubator and
the Berman Oropharyngeal Airway are superior in this role, all the airways
discussed here have major deficiencies in their function. Further research is
needed in this field to meet the requirements of endoscopists in situations when
it is crucial that equipment reliably fulfils its function.
PMID- 17031086
TI - Simulation and airway-management training.
AB - PURPOSE OF REVIEW: Simulators can be used to teach simple technical skills or
used in more realistic settings to teach or assess various cognitive/affective
skills. Although simulators have become widespread, their use and efficacy in
these various areas have not been delineated and are still being explored. This
review will discuss the present state of using medical simulation for airway
management training. RECENT FINDINGS: Airway management includes both specialized
technical skills and higher-order cognitive skills and behaviors. Since no one
simulator is capable of covering all the functions necessary to teach these
varied skills, medical specialists will need to train on a couple of different
simulators. Now widely accepted in medical education, simulator training is being
mandated in certain situations at some institutions because of a belief that it
alters the physician. In this article its efficacy in teaching the specific
psychomotor skills of bronchoscopy were validated but its use in teaching higher
cognitive skills remained inconclusive. SUMMARY: Simulators are here to stay.
Presently their usage in teaching psychomotor skills has scientific validity in
specific tasks but their efficacy for teaching higher-order cognitive skills is
still evolving. Future studies will continue to delineate the usage in different
areas by studying the outcome in skills training and retention.
PMID- 17031087
TI - The carrier gas in anaesthesia: nitrous oxide/oxygen, medical air/oxygen and pure
oxygen.
AB - PURPOSE OF REVIEW: The gas passing the module for the delivery of inhalation
anaesthetics and carrying vapourized anaesthetics into the breathing system is
called the carrier gas. Oxygen is the absolutely indispensable component of the
carrier gas. Additive gaseous components can be medical air (nitrogen), nitrous
oxide, cyclopropane, or xenon, the latter three being anaesthetic gases
themselves. Cyclopropane is not used any more and xenon is not approved as a
medical gas yet, leaving medical air and nitrous oxide as the only currently
available adjuncts to oxygen. RECENT FINDINGS: As review articles on nitrous
oxide recommend unequivocally not using this gas routinely, and many
anaesthetists already consistently omit any use of this gas, the alternative
carrier gases are either a mixture of medical air and oxygen or pure oxygen. A
nitrogen/oxygen mixture is absolutely inert with respect to metabolism or
environment; there are no contraindications or shortcomings at all. The use of
pure oxygen will result in high oxygen concentrations, improving the patients'
safety by increasing the pulmonary oxygen reservoir and rendering impossible the
development of hypoxic gas mixtures within the breathing system. Whether the
incidence of postoperative wound infections or postoperative nausea and vomiting
is reduced by perioperative hyperoxia is still under scientific discussion. In
general, the use of high oxygen concentrations over a period of 6-8 h is not
harmful for the patient, assuming the performance of recruitment manoeuvres,
consistent use of positive end-expiratory pressure, and thorough observance of
the contraindications that can result from the increased vulnerability of tissues
to hyperoxia. SUMMARY: Nitrous oxide should not be used routinely as a component
of the carrier gas any more. A mixture of medical air and oxygen must be
acknowledged to be the gold standard. Pure oxygen may be used as a carrier gas if
medical air or properly performing flow controls for medical air are not
available.
PMID- 17031088
TI - Capnometry in the spontaneously breathing patient.
AB - PURPOSE OF REVIEW: Capnography has been used in the operating room by
anesthesiologists for over a decade. Along with pulse oximetry, it has reduced
anesthesia-related morbidity and mortality. Traditionally, capnography has been
used to confirm the placement of the endotracheal tube. This review looks into
the literature for an update on the use of capnography in the spontaneously
breathing patient. RECENT FINDINGS: Several studies support the additional safety
afforded by the use of capnography in patients undergoing sedation for procedures
in various situations outside the operating room. Capnography has been used as an
aid in the diagnosis of pulmonary embolism and sleep-related disorders, as a
continuous monitor of metabolic status of pediatric patients with diabetic
ketoacidosis and, along with pulse oximetry, in lung-function laboratories to
estimate blood gases. SUMMARY: Capnography has become a mandatory or recommended
monitoring tool in the practice of anesthesiology. It is making inroads into
other medical specialties as a monitoring and diagnostic tool. The use of this
technology by non-anesthesiologists will continue to increase. In the opinion of
the authors capnography should be used in all cases requiring sedation either in
or out of the operating room.
PMID- 17031089
TI - Cutaneous carbon dioxide monitoring in adults.
AB - PURPOSE OF REVIEW: Arterial blood gas analysis is the 'gold standard' method to
measure the arterial partial pressure of carbon dioxide (PaCO2). However,
arterial sampling including arterial catheterization is invasive and expensive.
Cutaneous carbon dioxide tension (PcCO2) measurement is used as a noninvasive
surrogate measure of PaCO2, which is used to either estimate PaCO2 or determine
trend changes in the measurement. There has been considerable progress in the
technical aspects of PcCO2 monitoring in the last few years. In this article, we
evaluate recent developments and the renewed interest in the subject of PcCO2
monitoring in adults and discuss the technical aspects, clinical applications and
the future outlook for this technique in the clinical setting. RECENT FINDINGS:
With evolution in technology, PcCO2 monitoring is now less cumbersome than
before. Combined PcCO2 measurement and pulse oximetry is now possible with a
single earlobe sensor. SUMMARY: The clinical settings in which PcCO2 monitoring
can be applied include patient monitoring during and after anaesthesia, patients
receiving noninvasive ventilation, post extubation, endoscopy under sedation, the
sleep laboratory and the lung function laboratory. Although there is an overlap
of the clinical indications when both PcCO2 and end-tidal carbon dioxide
monitoring may be used, it is our opinion that both these methods have
independent indications and are sometimes also complementary to each other in
patient care.
PMID- 17031090
TI - Bibliography current world literature.
PMID- 17031091
TI - Pride and prejudice: inflammatory bowel disease models and drug development.
PMID- 17031092
TI - Genomics and inflammatory bowel disease.
AB - Genomic technologies offer new approaches to the investigation of etiology and
pathophysiology of inflammatory bowel disease (IBD). Several areas of application
for these new technologies are possible. One such application is the search for
gene variations predisposing to the development of the disorder in multiply
affected families. Genome-wide linkage studies have defined replicated
susceptibility regions for IBD on chromosomes 6, 12, and 16. These susceptibility
regions are still very large and each contain several hundred positional
candidate genes. Efforts are under way at several centers to define the
underlying molecular variants using systematic linkage disequilibrium and
candidate gene methods. The pharmacogenetic investigation of gene variations may
predict response to certain medications to target these therapeutic interventions
more precisely. The use of global gene expression technologies may allow the
identification of new pathways or molecules in the inflammatory process. This
seems to be especially relevant because currently only approximately 8,000 of the
estimated 100,000 human genes are characterized. In summary, genomic
methodologies will profoundly influence the progress of IBD research and may lead
to novel insights into both etiology and pathophysiology of chronic intestinal
inflammation.
PMID- 17031093
TI - Immunology of inflammatory bowel disease.
AB - The immunology of inflammatory bowel disease continues to be an intense area of
investigation for clues to the pathogenesis of Crohn disease and ulcerative
colitis. As typical with complex diseases, inflammatory bowel disease research is
continuously evolving. Without abandoning traditional areas of study, such as
humoral and cellular immunity and cytokines, investigation is broadening to
explore new molecules and biologic phenomena. Novel cytokines and cell adhesion
molecules appear to be involved in inflammation, while the role of nitric oxide
is being clarified. Leukocyte resistance to apoptosis appears to be a major
contributing factor to Crohn disease. Epithelial cell-derived defensins and
receptors are arising as key molecules mediating the interaction of innate and
acquired mucosal immunity with the enteric flora, and explaining how the latter
participates in gut inflammation. The results of these combined studies are
opening novel therapeutic horizons whose implementation offers better forms of
treatment.
PMID- 17031094
TI - Discovering the cause of inflammatory bowel disease: lessons from animal models.
AB - The precise cause of inflammatory bowel disease remains unclear. Relevant animal
models are important tools for studying the underlying mechanisms of inflammation
and disease pathogenesis. The purpose of this review is to summarize the various
types of animal models available for use in inflammatory bowel disease research
and to illustrate how these models have contributed to a better understanding of
the etiopathogenesis of inflammatory bowel disease, particularly focusing on
papers published during calendar year 1999. Studies using appropriate animal
models have provided important discoveries in this field of investigation. These
include determination of the key role that pathogenic and regulatory T cells,
proinflammatory and immunoregulatory cytokines, indigenous bacterial flora, and
putative predisposing genes play in the disease process. The availability of new
animal models that closely resemble the human disease is expected to allow
further characterization of the initiating event(s) in inflammatory bowel disease
and lead to a possible cure for this devastating disease.
PMID- 17031095
TI - Therapy for Crohn disease.
AB - Medical therapy for Crohn disease has advanced incrementally: Small, non
definitive controlled trials of mesalamine continue to be reported, but the
results are not sufficient to change the conclusion of a large meta-analysis that
shows only marginal benefit of mesalamine in Crohn disease. Low-dose, controlled
ileal-release budesonide is not effective for preventing postoperative recurrence
of Crohn disease. A loading dose of intravenous azathioprine does not accelerate
the time to response in patients with steroid-treated Crohn disease; however,
standard azathioprine may work more quickly than previously reported.
Mycophenolate mofetil may be therapeutically equivalent to azathioprine for
active Crohn disease. There is a trend toward benefit of oral methotrexate (15
mg/wk) for active Crohn disease, and there is no significant difference in the
blood concentrations of methotrexate in patients with inflammatory bowel disease
who receive methotrexate (15 or 25 mg weekly) administered subcutaneously.
Results in a pilot study suggest that tacrolimus may close perianal fistulas in
patients with Crohn disease. The anti-tumor necrosis factor antibody infliximab
is effective in closing perianal and enterocutaneous fistulas and in maintaining
remission in patients with Crohn disease. Infliximab also leads to endoscopic and
histologic remission. There is a trend toward benefit of subcutaneous recombinant
interleukin-11 for active Crohn disease. Two pilot studies have shown that
thalidomide may be of benefit in patients with refractory Crohn disease.
PMID- 17031096
TI - Medical therapy for ulcerative colitis.
AB - Last year was not a banner year for developments in medical therapy for
ulcerative colitis. In contrast to the expansion of therapies for Crohn disease,
treatment for ulcerative colitis was evolutionary, at best, leading many patients
to seek alternative medical approaches. Nevertheless, there have been advances in
the application of aminosalicylates and immune modifiers for ulcerative colitis.
Additional, nonconventional approaches include nicotine, probiotics, dietary
therapies, and heparins. Several novel approaches have arisen from animal models,
including additional means of inhibiting nuclear factor-kappaB and targeting of
tumor necrosis factor-alpha.
PMID- 17031097
TI - Clinical features of inflammatory bowel disease.
AB - The purpose of this review is to highlight new developments during the past year
regarding diagnosis and clinical features of inflammatory bowel disease.
Endoscopy remains the cornerstone for diagnosis and evaluation of ileocolonic
inflammatory bowel disease. In ulcerative colitis, recent studies have challenged
the concept of a continuous and homogeneous inflammatory process with constant
rectal involvement: patchy inflammation and rectal sparing were reported in
treated ulcerative colitis, and frequent cecum and appendiceal orifice skip
lesions were confirmed. Cross-sectional imaging techniques usefully complement
endoscopy by assessing whole-bowel thickness and detecting abscesses and
fistulae. Furthermore, echo Doppler ultrasound is able to measure mesenteric
blood flow, which is increased in active inflammatory bowel disease and seems to
parallel inflammatory disease activity. Osteopenia, which affects approximately
half of patients with inflammatory bowel disease, can be detected by dual-energy
x-ray absorptiometry and prevented. Hyperhomocysteinemia, a predisposing factor
for thrombosis, seems to be more frequent in inflammatory bowel disease, and can
be corrected by folate supplementation. The concept of an aggressive, penetrating
form of Crohn disease with early postoperative recurrence as opposed to a more
indolent, nonpenetrating form of the disease, with later recurrence, was recently
challenged. The most significant predictor of the risk of malignancy in
inflammatory bowel disease remains the presence of dysplasia in colonic biopsy
specimens. A dysplastic polypoid lesion or mass is a strong predictor of cancer
but should be distinguished from the dysplasia inherent in a coincident sporadic
adenoma.
PMID- 17031098
TI - Diagnostic markers of inflammatory bowel disease.
AB - The diagnosis of inflammatory bowel disease is usually straightforward, based on
a detailed history and physical examination, along with standard radiographic and
endoscopic investigations, biopsies, and laboratory parameters. More challenging
is the search for clinically useful, noninvasive markers for Crohn disease and
ulcerative colitis to accurately screen cases with nonspecific and indolent
symptoms. Equally required are diagnostic markers that discriminate between these
two disorders in cases with indeterminate colitis. Another dilemma for clinicians
is that there are no simple measures to observe disease activity and predict
relapses. This review describes the recent advances in diagnostic markers that
afford the ability to screen for inflammatory bowel disease, discriminate between
its types, and monitor disease activity. These include serological, fecal, and
tissue markers; permeability tests; and diagnostic imaging using color Doppler
ultrasonography.
PMID- 17031099
TI - Atypical forms of inflammatory bowel disease: microscopic colitis and pouchitis.
AB - Three atypical colitides (and enterides) are collagenous colitis, lymphocytic
colitis, and ileal pouchitis. Collagenous and lymphocytic colitis are similar
inflammatory bowel disorders of unknown cause with symptoms including chronic
watery diarrhea, occurring in middle age. Pouchitis is the most significant long
term complication in patients with ileoanal pouch anastomosis. The clinical and
histologic features and management of these entities are discussed.
PMID- 17031100
TI - Esophageal disorders.
PMID- 17031101
TI - Gastroesophageal reflux disease.
AB - Gastroesophageal reflux disease (GERD) is a common chronic disorder affecting
millions of people worldwide. This is a review of a number of published studies
in the past year that increase current understanding or raise important issues
about this disorder. Among the areas covered are the epidemiology and role of
genetics in GERD; its pathogenesis with respect to duodenogastric reflux and
impaired epithelial barrier function; the effects of atropine on transient lower
esophageal sphincter relaxations; the role of acid suppression, heat shock
proteins, and the enzyme cyclooxygenase-2 in Barrett esophagus and esophageal
adenocarcinoma; the complication rates in laparoscopic fundoplication; and the
results of ablation therapy for the treatment of Barrett esophagus and esophageal
adenocarcinoma. These investigations reinforce a sense of the complexity of GERD
and provide optimism that modern technology will continue to be used to develop
more effective treatments.
PMID- 17031102
TI - Esophageal motor disorders.
AB - Motor dysfunction is responsible for symptomatic illnesses both in the proximal
skeletal muscle region and in the distal smooth muscle esophagus. Practical
methods for diagnosing and treating oropharyngeal dysphagia continue to reach
consensus. Achalasia, the most significant of the distal motor disorders, is of
investigative interest because of the expanded armamentarium of treatment
options. Minimally invasive surgical methods have taken an important foothold as
a primary treatment of this disorder. Appreciation is growing for sensory
dysfunction that accompanies distal motor disorders. Such dysfunction may help
explain the observed discrepancies between symptoms and measurable motility
abnormality.
PMID- 17031103
TI - Chest pain of esophageal origin.
AB - Patients with unexplained chest pain remain a difficult and perplexing challenge
for the gastroenterologist. Despite exclusion of a cardiac origin many patients
remain disabled by pain. In these, a diligent search for an esophageal cause
gastroesophageal reflux disease, motility abnormalities, or esophageal
hypersensitivity using all available diagnostic (therapeutic) tools-results in a
positive outcome. Appropriate use of a diagnostic trial of therapy, ambulatory pH
monitoring and/or esophageal manometry, necessitates understanding of the
respective benefits. The recent literature examines the value of a short course
of high-dose proton pump inhibitors in establishing a diagnosis of
gastroesophageal reflux disease-associated chest pain, the use of tricyclic
antidepressants, and behavioral therapy in the management of these difficult
patients with nonreflux, noncardiac chest pain.
PMID- 17031104
TI - Barrett esophagus.
AB - Barrett esophagus continues to intrigue investigators and clinicians alike as the
new millennium begins. A large number of publications in the past year have
discussed issues of epidemiology, prevalence, detection, and treatment of Barrett
esophagus. Chronic symptoms of gastroesophageal reflux were identified as a
strong risk for esophageal adenocarcinoma. The relative frequency of short and
long Barrett and cardia intestinal metaplasia in patients who undergo upper
endoscopy have been better defined. Biomarkers in patients with Barrett may
eventually be helpful in identifying those at high risk for the development of
neoplasia. High-dose proton pump inhibition to the point of near elimination of
esophageal acid exposure remains disappointing in its impact on the surface area
of Barrett. Finally, the developments in endoscopic therapy for patients with
Barrett esophagus continue to be promising.
PMID- 17031105
TI - Endoscopic therapeutic esophageal interventions.
AB - At the close of the 20th century, therapeutic endoscopy in the esophagus has
expanded to encompass a broad array of interventions. As the number of procedures
grows, emphasis in the medical literature has begun to shift to analyses of which
procedures should be performed. Many studies published in 1999 on topics ranging
from endoscopic treatment of benign and malignant strictures, to variceal
bleeding, to Barrett esophagus have focused on which of several methods provides
the best long-term response with the fewest interventions. This is a review of
the major published studies of endoscopic interventions in the esophagus as well
as selected abstracts. The conclusions of these studies and reports of new
endoscopic therapies draw a clear map of where nonoperative esophageal
therapeutics are headed in the next several years.
PMID- 17031106
TI - Esophageal cancer.
AB - Papers published in the English literature on esophageal cancer in 1999 were
retrieved by a MEDLINE search. Selective publications were reviewed in light of
current knowledge. Many studies were performed to refine staging methods of
esophageal cancer, especially in the use of endoscopic ultrasound. Although
better designs have overcome the problem of nontraversable tumors, its use in
staging after neoadjuvant therapies remains suboptimal. Important studies on
various surgical techniques were reported, including randomized trials on
different routes of reconstruction after esophageal extirpation, and the updated
results of transhiatal resections. In contrast to the minimalist approach of
transhiatal resection, investigators from both East and West have also described
the pathologic basis of lymphatic spread of esophageal cancer and its
implications, favoring more radical lymphadenectomy. Another avenue that was
explored is the use of neoadjuvant therapies to improve outcome. Different
regimens were studied, and many papers focused on the molecular prediction of
favorable response to such therapies. Overenthusiastic adoption of multimodality
treatments is cautioned, however, in that they have not been validated. Further
work is much needed in this area of research.
PMID- 17031107
TI - Surgery, radiotherapy, and chemotherapy in carcinoma of the esophagus.
AB - Esophageal carcinoma remains a highly lethal disease that has shown a recent
profound increase in prevalence and an equally dramatic epidemiologic shift.
There is a well recognized causal association between gastroesophageal reflux
disease and adenocarcinoma of the esophagus, and the molecular events underlying
this progression from mucosal injury, to metaplasia, to dysplasia, to carcinoma
are now becoming clear. Current diagnostic modalities and preoperative staging
systems all have significant limitations. Fortunately, chemoprevention strategies
and the identification of clinically useful molecular biomarkers that may be used
to stage disease and select appropriate therapy are on the horizon. The extent of
surgical resection for esophageal carcinoma remains an area of great controversy.
Disease that is confined to the mucosa is being diagnosed more commonly, and
endoscopic ablative techniques have been proposed. To date, however, preoperative
discrimination of tumor depth and presence of regional nodal metastases remains
inadequate in these very early lesions, and caution is urged before adopting
therapies that may compromise cure. For disease penetrating the mucosa, the
extent of surgical therapy must be tailored by the objectives of treatment (cure
vs palliation) and preoperative stage. Surgical resection is the current standard
of care, with combined-modality therapy reserved for prohibitive surgical
candidates. No clear survival benefit has been documented for neoadjuvant
radiotherapy or chemotherapy alone. The results of preoperative combined-modality
therapy, including three prospective, randomized trials, are encouraging but to
date have not shown a definite benefit.
PMID- 17031108
TI - Bibliography current world literature.
PMID- 17031110
TI - Signal transduction in pancreatic acinar cell physiology and pathophysiology.
AB - The pancreatic acinar cell is a valuable cell model for understanding how
activation of plasma membrane receptors generates signals that propagate,
amplify, diversify, and integrate to control cellular function. A primary
signaling system involves the activation of heterotrimeric G proteins that
stimulate phospholipases, leading to the generation of phospholipid messengers. A
major action of the phospholipid messengers is the control of cytoplasmic Ca(2+)
levels. The complex mechanisms involved in controlling the initiation, form, and
spatial pattern of Ca(2+) release are being revealed in increasing detail and
complexity. The connections between the signaling networks and the final events
of secretion are beginning to be revealed. Advances have also been made in
understanding the processes that underlie the pathologic effects of receptor
overactivation.
PMID- 17031111
TI - Acute pancreatitis.
AB - Acute pancreatitis is a process that continues to interest physicians and
research scientists. Understanding potential factors initiating acute
pancreatitis, mechanisms regulating the local and distant inflammatory response,
methods for accurately predicting outcome, and possible therapeutic interventions
continue to be investigated. Current interest in inflammatory response of the
acute injury focuses on proinflammatory and anti-inflammatory cytokines as
markers for disease severity and predictors of outcome. Recent studies confirm
the utility of physical examination and existing markers such as C-reactive
protein and interleukin-6 in predicting the severity of acute pancreatitis.
Understanding the molecular mechanism of lung injury remains a major focus for
future therapeutic targets, since pancreatitis-associated pulmonary injury
results in significant morbidity and is a major indication for intensive care
unit admissions.
PMID- 17031112
TI - Chronic pancreatitis.
AB - In the past year, there has been at least one important clinical paper that sheds
light on the character and natural history of painful chronic pancreatitis, which
has important clinical implications. In addition, several novel mutations have
been described in the cationic trypsinogen gene in patients with hereditary
pancreatitis. The mechanism by which these mutations cause pancreatic disease
remains speculative. The diagnosis of early chronic pancreatitis is
controversial. A novel noninvasive pancreatic function test (measurement of
postprandial APOB-48) was reported but is unlikely to be a sensitive test of
pancreatic function. Pancreatic fibrosis is frequently seen in alcoholics without
chronic pancreatitis, and this makes it difficult to interpret the findings on
endoscopic ultrasonogram. Recent studies highlight the difficulty in abolishing
pancreatic steatorrhea. Recently fibrosing colonopathy in adult patients has been
reported. Extracorporeal shockwave lithotripsy combined with endoscopic therapy
failed to benefit patients with calcific chronic pancreatitis.
PMID- 17031113
TI - Molecular genetics of ductal pancreatic neoplasia.
AB - The molecular genetic profiles that characterize pancreatic ductal neoplasia have
taken shape recently with the help of immunohistochemistry and the establishment
of the nomenclature describing pancreatic ductal tumorigenesis. K-ras mutations
frequently occur early, changes in the expression and genetic integrity of the
p16 gene appear in intermediate lesions, and the inactivation of the p53, DPC4,
and BRCA2 genes occur late in the neoplastic progression. Tumor-suppressor genes
inactivated in pancreatic cancer such as ALK5, TGFBR2, MKK4, and STK11/LKB1 have
been identified, although their roles in tumor progression are not yet well
defined. Additional discoveries in this tumor system may be on the horizon, will
further refine the molecular genetic profiles for the disease, and should suggest
some clinical uses for this fund of knowledge.
PMID- 17031114
TI - Pancreatic surgery.
AB - Several important advances in pancreatic surgery have been made over the past
year. As in other areas of general surgery, laparoscopic techniques are being
used with increasing frequency, but their real value remains to be determined.
Methods to stage pancreatic cancer, perform palliative bypass, relieve pain, and
perform distal pancreatic resections have been described. Using more conventional
surgical approaches, data continue to accumulate about pylorus preserving
pancreaticoduodenectomy as an alternative to the standard operation. The survival
benefit of extended pancreatic resection for pancreatic cancer remains dubious.
Studies continue to demonstrate lower morbidity and mortality rates for
pancreaticoduodenectomy performed at high-volume centers. In the arena of chronic
pancreatitis, pain relief is still the most common reason for surgical treatment,
and the efficacy of various operations has been assessed by some new studies.
Data continue to show that aggressive surgical treatment for infected necrosis
leads to improved survival in patients with severe acute pancreatitis.
PMID- 17031116
TI - Biliary tract physiology.
AB - Cholangiocytes, the cells lining the bile ducts, are now recognized as important
contributors to and modulators of bile formation. During the last few years,
remarkable insights have been made into the mechanisms of fluid, electrolyte, and
solute transport by biliary epithelia, as well as increasing knowledge of the
complex endocrine, paracrine, and neurologic factors regulating bile formation.
Advances in the past year include an increased understanding of the interaction
between bile acids and cholangiocytes in the regulation of bile formation in
normal and cholestatic states and greater insight into the pathogenic mechanisms
of biliary diseases. References to recent comprehensive reviews of specific areas
of biliary physiology are provided, and new experimental models are also
described.
PMID- 17031117
TI - Biliary tract cancer.
AB - Investigation into the molecular and cellular biology of carcinogenesis continues
to elucidate potential mechanisms for the initiation and progression of biliary
tract cancer. The potential role of cell cycle regulators, such as Fas ligand,
has been examined in the etiology of bile duct carcinoma. In addition, there is
evidence for a possible link between chronic inflammation and malignant
transformation through the relation between nitric oxide and DNA repair enzymes.
Noninvasive imaging modalities, including helical computed tomography scanning,
magnetic resonance cholangiopancreatography (MRCP) and positron emission
tomography (PET) scanning, are gaining acceptance and may eventually supplant
standard methods of evaluation. In addition, innovative tissue-sampling
modalities including choledochoscopy are being developed. Several large series,
Japanese and Western, continue to report improved 5-year survival rates after
aggressive surgical resections of hilar cholangiocarcinoma. Although
chemotherapeutic options remain limited in biliary tract carcinoma, radiation
therapy may provide a benefit in local control in patients with microscopically
positive margins. Photodynamic and multimodality therapy also may become
important components of improving palliation for patients with advanced disease.
PMID- 17031118
TI - Sclerosing cholangitis.
AB - Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown
etiology. Immunogenetic factors are considered important in its pathogenesis. The
genetic susceptibility to primary sclerosing cholangitis is associated, in part,
with the HLA HLA-DRB1, DQA1, DQB1 haplotype. Liver histology in primary
sclerosing cholangitis is characterized by a portal inflammatory infiltrate
mostly composed of memory T cells. Many patients eventually will develop
cholangiocarcinoma, and inactivation of the p16 tumor-suppressor gene might be
involved in neoplastic transformation. Alcohol consumption might be a risk factor
for cholangiocarcinoma, and, in some patients, elevation of serum CA19-9 marks
the neoplastic transformation. To date, no medical treatment has been proven
effective. Endoscopic therapy might be useful in some patients, but controlled
studies are lacking. Liver transplantation remains the only effective treatment.
Posttransplant survival and quality of life are continuously improving despite
the fact that the disease may recur in some patients after transplantation.
Nevertheless, patient selection and timing of indication for liver
transplantation remain uncertain.
PMID- 17031119
TI - Gallstones.
AB - At the turn of the millennium, significant advances continue to be made into the
epidemiology and pathophysiology of gallstone disease. The NHANES III study, the
largest American population-based study of gallstone disease, estimated that more
than 20 million Americans have undergone gallbladder surgery or currently have
gallstones. Insulin resistance may be an independent risk factor for gallstone
disease.Cholecystokinin receptors may be responsible for the altered motility of
the gallbladder smooth muscle, and mucin may play an underestimated role as a
pronucleating factor. For the first time, researchers have been able to directly
observe cholesterol crystallization in human bile. Improved understanding of the
multiple factors involved in the pathogenesis of gallstone disease should lead to
new therapeutic and preventive strategies.
PMID- 17031121
TI - Bibliography current world literature.
PMID- 17031120
TI - Endoscopic management of biliary disease.
AB - Endoscopic management of biliary disease remains at the forefront of minimally
invasive means of providing therapy, as well as contributing important diagnostic
information in complex clinical scenarios. The authors review recent advances and
reported trials of therapy and revisit important controversial issues. The
management and diagnosis of choledocholithiasis are discussed, as well as
endoscopic techniques for attaining biliary access at endoscopic retrograde
cholangiopancreatography. In addition, management of biliary anastomotic
strictures in liver transplant patients, role of cholangioscopy, and recent
advances in stent technology are reviewed.
PMID- 17031122
TI - Stomach and duodenum.
PMID- 17031123
TI - Gastric secretion.
AB - This article summarizes data published during the past year that improve our
understanding of the mechanisms by which various neurotransmitters, paracrine
agents, and hormones regulate gastric acid secretion and are themselves
regulated. The main stimulants of acid secretion are histamine, gastrin, and
acetylcholine. The main inhibitor is somatostatin, which exerts a tonic restraint
on parietal, enterochromaffin-like (ECL), and gastrin cells. Histamine, released
from ECL cells, stimulates the parietal cell directly via H(2) receptors and
indirectly via H(3) receptors coupled to inhibition of somatostatin secretion.
Gastrin, acting via gastrin/cholecystokinin-B (CCK-B), now termed CCK(2),
receptors on ECL cells activates histidine decarboxylase, releases histamine, and
induces ECL hypertrophy and hyperplasia. The latter might be responsible for the
rebound hyperacidity observed after withdrawal of long-term antisecretory
therapy. The neurotransmitter pituitary adenylate cyclase-activating polypeptide
stimulates histamine secretion from isolated ECL cells, but its physiologic role,
if any, is not known. Acetylcholine, released from gastric postganglionic
intramural neurons, stimulates the parietal cell directly via muscarinic M(3)
receptors and indirectly by inhibiting somatostatin secretion. Although infection
with H. pylori is associated with increased basal and stimulated acid outputs in
patients with duodenal ulcer, most people infected with the organism are
asymptomatic and have pangastritis with decreased acid output. In the latter,
eradication of the bacterium leads to an increase in gastric acidity and is
associated with a two-to threefold increase in gastroesophageal reflux.
PMID- 17031124
TI - Gastroduodenal mucosal defense.
AB - The gastroduodenal mucosa is a model system of defense with several structural
levels and biologic strategies that are closely interrelated with each other to
cope with the harmful ingredients of ingested food and the potentially
deleterious effects of gastric acid and pepsin. Experimental and clinical
research carried out during the review period added to the understanding of each
component of the multiple mechanisms of gastroduodenal mucosal protection. In the
first place, mucosal integrity is defended by the mucus gel barrier, the
epithelial cell barrier, and the immune barrier. The properties of these barriers
are maintained by adequate regulation of mucus production, bicarbonate secretion,
mucosal microcirculation, and motor activity. These regulatory systems are
alarmed by nociceptive neurons and the mucosal immune system which includes
chemokine-secreting epithelial cells. The ultimate defense system is rapid repair
of the injured mucosa under the control of several growth factors. Progressing
insight into the network of mucosal defense not only will improve existing
therapies of inflammation and ulceration but also will provide new leads for the
management of functional diseases in the gastroduodenal region.
PMID- 17031125
TI - Gastroduodenal motility.
AB - During the past year there were significant developments in the area of
gastroduodenal motility--in basic physiology, pathophysiology, diagnosis, and
therapy. Some represented a major breakthrough; most were incremental. Evidence
continues to accumulate to support an important role for the stomach in the
regulation of food intake, and the physiologic mechanisms involved continue to be
revealed. Although there were no dramatic developments in the area of diagnostic
methodology, several studies sought to refine or to extend the use of currently
available techniques. Gastric motor activity and that of the proximal stomach
continue to attract attention in dyspepsia and gastroesophageal reflux disease,
and the range of disorders that may disrupt the motor function of the stomach
continues to extend. On the therapeutic front, advances were largely in refining
the indications and the uses of available therapies, rather than in the
development of novel agents.
PMID- 17031126
TI - The treatment of peptic ulcer disease.
AB - There is a continuation of the debate on the management of dyspepsia while the
role of Helicobacter pylori in duodenal ulcer disease is being questioned with
renewed vigor, specifically in the United States. The interaction of NSAIDs and
H. pylori provided some interesting, if at times confusing, literature while the
debate on the safety of long-term acid suppression remained unresolved. There
were some interesting developments with regard to therapeutic agents during this
period. A fourth proton pump inhibitor was introduced to the market while
cisapride, a drug previously considered safe, was effectively withdrawn from the
North American market because of safety concerns. More data on the COX-1-sparing
agents became available, and their impressive gastrointestinal safety profile was
confirmed. It was noted, however, that the incidence of dyspepsia, experienced by
users of these drugs, may remain a problem.
PMID- 17031127
TI - NSAID gastrointestinal toxicity.
AB - Toxic effects in the upper gastrointestinal tract, primarily complicated gastric
and intestinal ulcers, are the most common undesirable effects of the
nonsteroidal antiinflammatory drugs (NSAIDs). During the last several years there
have been several advances, both in the laboratory and clinically, toward
reducing NSAIDs' gastrointestinal toxicity. Some of these important developments
have been the delineation of mechanisms of NSAID-induced GI toxicity,
identification of groups at highest risk for development of NSAID-induced
gastrointestinal complications, recognition of co-therapies that could reduce
NSAID toxicity, and, most recently, development of classes of NSAIDs that have an
improved gastrointestinal safety profile. Many of these advances occurred during
the last year. This review focuses on several of the important recent
observations that have improved our understanding and the safety of NSAIDs in the
gastrointestinal tract.
PMID- 17031128
TI - Nonulcer dyspepsia.
AB - New definitions of functional disorders in general and nonulcer dyspepsia in
particular were published in the period of review. Although the definition of
functional dyspepsia as persistent or recurrent unexplained upper abdominal pain
or discomfort stayed essentially the same, new definitions of dyspepsia subgroups
were introduced based on the predominant symptom; a reflux-like dyspepsia
subgroup was not supported. It is hoped that these criteria, derived by a
consensus among international experts in the field, will improve the reliability
and the interpretability of future epidemiologic and interventional studies. A
wide range of studies dealt with the role of putative etiological factors in
functional bowel disorders including Helicobacter pylori, altered visceral
sensation, or upper intestinal motility. Although eradication of H. pylori does
not seem to relieve dyspepsia over placebo in recent studies of nonulcer
dyspepsia, eradication of H. pylori has generally been advised because of
suspected beneficial long-term effects (eg, treatment of misdiagnosed ulcer
disease) that probably overweigh the potential risks.
PMID- 17031129
TI - Interventional procedures.
AB - During the past year, numerous articles were published on interventional
procedures of the stomach, focusing on upper gastrointestinal tract bleeding,
gastric cancer, gastric outlet obstruction, and benign disease. In the area of
upper gastrointestinal tract bleeding, early endoscopy is warranted for early
therapeutic intervention and for triage. In patients with bleeding related to
peptic ulcer disease, combination therapy (epinephrine injection in conjunction
with electrocoagulation therapy) remains the standard of care. Hemoclipping is a
new technique that may be helpful in cases in which conventional therapy fails.
Repeat endoscopy should always be considered in patients in whom the first
attempt at endoscopic therapy fails. In patients with bleeding related to portal
hypertension, prophylactic antibiotics may decrease the risk of infections.
Banding remains the therapy of choice for this group of patients. There is no
documented benefit for combination therapy (banding and sclerotherapy).
Transjugular intrahepatic portosystemic shunts may be helpful in the treatment of
hypertensive portal gastropathy but not gastric vascular ectasias. In the area of
gastric cancer, management revolves around staging. This can be accomplished best
through the use of CT scan and endoscopic ultrasound. In patients with early
limited disease, attempt at endoscopic mucosal resection should be considered.
This technique can be performed in a variety of ways: the most common method
seems to be through the use of a saline injection, to separate the mucosa
submucosal layer, followed by a cap-assisted snare resection with suction. The
safety, efficacy, and outcome of this technique are reviewed. Gastric outlet
obstruction remains a difficult problem to treat endoscopically. However, there
is some evidence that endoscopic therapy may be successful in benign disease and
should be considered prior to surgical intervention.
PMID- 17031130
TI - Gastric cancer.
AB - Gastric adenocarcinoma is the most common malignancy of the upper
gastrointestinal tract. During the past two decades it has migrated toward the
gastroesophageal junction. Gastroesophageal reflux and obesity may play a role.
Recent research suggests that a number of biologic and molecular differences
exist in patients with gastric cancer. Further investigation in these areas may
help in predicting outcome and directing therapy. Gastric cancer is not a curable
condition when metastases are present. However, postoperative chemotherapy plus
chemoradiotherapy, in the Intergroup trial 0116, prolonged the overall and
disease-free survival rates of patients after a curative (R0) resection. It
should be considered the new standard of care in patients with gastric cancer who
have undergone curative resection with stage Ib-IV disease. Preoperative therapy
strategies may increase the likelihood of R0 resection and remain an area of
active investigation. Finally, development of more active agents is needed for
the treatment of metastatic tumors.
PMID- 17031131
TI - Gastroduodenal disorders in children.
AB - Studies within the past year examining the mechanisms underlying infantile
hypertrophic stenosis at the cellular and molecular level are reviewed. A number
of new modalities, including electrogastrography, and the 13C octanoid acid
breath test have been used in the study of normal and abnormal gastrointestinal
motility, as well as for the characterization of patterns of development of
gastric motility in early infancy. Several studies pertaining to the natural
outcome, the mode of transmission, and the associated symptomatology of
Helicobacter pylori were published, attesting that, despite the tremendous
progress achieved in our understanding of H. pylori, important gaps remain in our
knowledge of this microorganism. Newly described clinical presentations of
eosinophilic gastroenteritis and food allergy will also be of interest to the
reader.
PMID- 17031133
TI - Epithelial cell antigen presentation.
AB - For decades intestinal epithelial cells were thought of as passive barriers to
luminal contents, cells involved in nutrient absorption and electrolyte
secretion. Studies during the past 10 to 15 years have changed that concept as
our understanding of mucosal immunity has evolved and as we have come to
understand that the regulation of this system is unique in terms of cellular
interactions and factors produced. The intestinal epithelial cell has moved to
the forefront of these studies where it has been shown to be an active
participant in mucosal immunoregulation and inflammation. Results of the earliest
studies suggested that epithelial cells might be involved in immune regulation
because they expressed a series of cell surface molecules that correlate with
classical antigen presentation (class I and II MHC molecules). Later on, the
expression of nonclassical class I molecules was identified on these cells as
well, raising the possibility of novel forms of interactions with unique cell
populations. This was followed by the observation that epithelial cells secrete
cytokines and chemokines, which not only regulate mucosal immune responses but
also regulate inflammatory responses. By such processes, the IEC has been
proposed as being a bridge between innate and adaptive immunity. The recent
description of Toll-like receptors on IECs adds further support to this concept.
Clearly there is growing appreciation of the multifaceted role that the IEC plays
in the gut. The work on IECs in the past year has helped to refine this role.
PMID- 17031134
TI - The role of neuroenteric hormones in intestinal infectious diseases.
AB - It is now well established that communication among the enteric nerves, hormones,
and neuropeptides plays a role in the pathogenesis of infectious gastrointestinal
conditions. The results of several studies suggest that enteric nerves and
hormones modulate important gastrointestinal functions such as intestinal
motility and transport, intestinal permeability, fluid secretion, and
inflammation in response to infectious agents. During the past year several gut
brain peptides, including substance P, neurotensin, and galanin, emerged as
important mediators in the development and progress of intestinal infectious
conditions. The intestinal mechanism of neuropeptide and hormone action involves
direct effects via binding to receptors on the intestinal epithelium as well as
on immune cells localized underneath the epithelial layer. Based on the available
evidence from whole animal models it is possible that these new paradigms may
offer novel therapeutic strategies in the treatment of gastrointestinal
infections. This review summarizes recent progress on the identification of
peptide hormones participating in the pathophysiology of infectious intestinal
conditions and discusses the possible mechanism(s) of action involved in these
processes.
PMID- 17031135
TI - Transforming growth factor-beta: an important cytokine in the mucosal immune
response.
AB - Cytokines are important mediators in the intestine regulating both oral tolerance
and mucosal inflammation. Central to this immune-regulatory role is the cytokine
transforming growth factor-beta (TGF-beta). Oral tolerance and inflammatory
responses in the gut are regulated through the balance of the Th1, Th2, and Th3
lymphocyte responses--a balance influenced strongly by TGF-beta. TGF-beta also
modulates B-cell responses by increasing the production of immunoglobulin A (IgA)
while decreasing the production of IgG, IgM, and IgE. In intestinal epithelial
cells, TGF-beta activates signal transduction pathways resulting in the
inhibition of proliferation and tumorigenesis. Currently, these signaling
pathways are being dissected at the molecular level.
PMID- 17031136
TI - Innate immunity and the gut.
AB - The intestinal epithelium encounters a unique environment consisting of microbes,
both commensals and pathogens, as well as dietary nutrients and antigens. This
complex composition necessitates the presence of a dynamic system of defense to
contain both pathogenic and commensal bacteria within the lumen yet allow for
nutrient absorption. Tight junctions provide protection of the intercellular
spaces while other surface molecules, such as intestinal trefoil factor, help to
maintain the structural integrity of the epithelium. Other more active processes,
including upregulated expression and activation of antimicrobial peptides and
enhanced fluid secretion, provide a second level of innate defense. Despite
providing the interface between an exuberant immune system and a highly antigenic
lumenal environment, the intestinal epithelium must remain quiescent. As such,
several novel antiinflammatory mechanisms were recently identified. Studies that
elaborate the various aspects of these pathways are discussed in this review.
PMID- 17031137
TI - The immunologic basis for intestinal food allergy.
AB - There has been considerable recent broadening of basic concepts of intestinal
food allergy, in particular the importance of non-IgE-mediated mechanisms. The
traditional emphasis on IgE-mediated allergy now appears inappropriate in light
of current studies of the basic mechanisms of oral tolerance to dietary antigen
and of increasing recognition of the requirement for early infectious challenge
in the prevention of allergic sensitization. This major change in emphasis has
been forced both by basic scientific studies and by recognition of novel patterns
of food allergic disease within the pediatric population, in which rapid increase
in food-allergic sensitization has been noted in the last decade and previously
rare phenomena such as multiple food allergies and sensitization of exclusively
breast-fed infants to antigens eaten by the mother have become commonplace. It is
thus emerging that the possession of exaggerated IgE responses may not be the
direct cause of food allergic sensitization but may ensure that such
sensitization is clinically obvious. Those without such immediate responses have
a complex of symptoms, including diet-responsive eczema and a marked disturbance
of intestinal motility. The clear demographic links with socioeconomic privilege
and relative protection from gastrointestinal infarctions concord with recent
murine data suggesting an obligatory input from innate immune responses to the
gut flora in the establishment of oral tolerance.
PMID- 17031138
TI - Immunology of hepatitis C virus infection.
AB - Hepatitis C virus (HCV) is known for its ability to establish persistent
infection and cause chronic hepatitis in most infected individuals. The
pathogenesis of hepatic injury and the precise mechanisms underlying viral
persistence are unknown. Accumulating evidence indicates that successful
elimination of HCV is associated with the induction and maintaining of strong
helper T-cell and cytotoxic T-cell responses against multiple viral epitopes. In
contrast, patients who develop chronic HCV infection are characterized by the
lack of strong viral-specific helper T-cell responses. The failure to mount and
maintain strong HCV-specific T-cell responses may be determined by the genetics,
especially the major histocompatibility complex background, of the host. However,
it is likely that other host and viral factors are also involved in determining
the outcome of HCV infection. Available data suggest that HCV is not cytopathic
to hepatocytes and that liver injury associated with chronic HCV infection is
likely to be mediated by immune responses against HCV-infected hepatocytes. In
addition to hepatitis, HCV infection may also cause breaching of immune
tolerance, leading to autoimmune disorders. Although the lack of a small animal
model and a tissue culture system has impeded research on hepatitis C virus (HCV)
infection, recent studies in humans and chimpanzees have significantly enhanced
our understanding of the interaction between HCV and the host's immune system.
This review focuses on the most recent advances in our understanding of the
immunology of HCV infection. In particular, the possible mechanisms of how HCV
establishes chronic infection are discussed. The pathogenesis of liver injury,
the immunogenetics of HCV infection, and the effect of HCV infection on host's
immune function are also reviewed.
PMID- 17031139
TI - New immunologic treatments for inflammatory bowel disease.
AB - After many years with little progress in new treatments for patients with
inflammatory bowel disease, there is now rapid expansion of a new class of
immunologic agents. These agents are designed to disrupt proinflammatory pathways
at specific sites. Monoclonal antibodies to tumor necrosis factor-alpha (TNF
alpha) are already transforming the lives of some patients with previously
intractable Crohn disease, and further TNF-alpha directed therapies are being
developed. Clinical trials are now underway on agents that inhibit adhesion
molecules and antiinflammatory cytokines, while attempts are being made to
actively immunize against TNF-alpha. Promising data continue to be reported,
although long-term safety data are still mostly unavailable. Although these
agents are proving to be very effective in the treatment of patients with Crohn
disease, their use should continue to be restricted while indications and dose
regimens are defined.
PMID- 17031140
TI - Bibliography current world literature.
PMID- 17031142
TI - Bacterial infections: small intestine and colon.
AB - Bacterial enteric infections exact a heavy toll on human populations,
particularly among children. Despite the explosion of knowledge on the
pathogenesis of enteric diseases experienced during the past decade, the number
of diarrheal episodes and human deaths reported worldwide remains of apocalyptic
dimensions. However, our better understanding of the pathogenic mechanisms
involved in the onset of diarrhea is finally leading to preventive interventions,
such as the development of enteric vaccines, that may have a significant impact
on the magnitude of this human plague.
PMID- 17031143
TI - Rotavirus and calicivirus infections of the gastrointestinal tract.
AB - Virus infections of the gastrointestinal tract, leading to gastroenteritis, are a
common problem in both developed and developing countries. Rotavirus and Norwalk
like viruses are the most common agents responsible for clinically severe disease
in humans, and this paper focuses on new information about the mechanisms of
pathogenesis and epidemiology of these two pathogens. Rotavirus-induced disease
involves a viral enterotoxin and activation of the enteric nervous system, as
well as malabsorption, suggesting that common mechanisms of pathogenesis may
exist between viral and bacterial pathogens. Each gastrointestinal virus
possesses unique molecular properties that can be exploited to discover new
information about responses of cells of the gastrointestinal tract. Work
continues toward making vaccines for rotavirus and Norwalk-like viruses.
PMID- 17031144
TI - Emerging and reemerging intestinal protozoa.
AB - The intestinal protozoa have gained importance to physicians practicing medicine
in the United States, Canada, and Europe during recent years as a result of
increasing world travel, the globalization of the world's economy, and the
growing number of chronically immunosuppressed people. During the spring of 1996,
Cyclospora cayetanensis caused diarrhea in approximately 1500 people exposed to
Guatemalan raspberries. This epidemic recurred in 1997, emphasizing the risks of
the global economy and food supply on which we depend. In addition to importation
of intestinal protozoa from the tropics, AIDS and the increasing use of organ
transplants have created a new population of people at risk for chronic infection
by ubiquitous protozoa previously not known to cause serious human disease. These
infections include cryptosporidiosis, isosporiasis, and microsporidiosis.
Finally, Entamoeba histolytica, the etiologic agent of invasive amebiasis, has
only recently been recognized to be a distinct species from a nonpathogenic but
indistinguishable (by light microscopy) intestinal commensal, Entamoeba dispar.
The rapidly changing epidemiology of these intestinal protozoa, as well as new
approaches to diagnosis and treatment of these protozoa, are discussed.
PMID- 17031145
TI - Pathogenesis of Helicobacter pylori infection.
AB - Helicobacter pylori infects over half of the world population. Infection with the
bacterium causes gastritis and peptic ulcer disease and is associated with the
development of gastric cancers. However, only a small proportion of individuals
develop these complications of infection. Therefore, identification of both host
and bacterial factors that mediate disease is an intense area of current research
interest. This review highlights recent advances in understanding of the
mechanisms underlying disease pathophysiology following infection with H. pylori.
PMID- 17031146
TI - Treatment of Helicobacter pylori.
AB - Helicobacter pylori causes several gastroduodenal diseases. Various antibiotic
regimens are available that eradicate H. pylori in 80 to 90% of patients, but no
regimen cures all patients. Dual therapy is now obsolete. Triple therapy with two
antibiotics and either a proton pump inhibitor or bismuth is the regimens of
choice. Metronidazole and clarithromycin are the two key antibiotics. Antibiotic
resistance against these two drugs is becoming more problematic and should be
taken into consideration when choosing a regimen. Antibiotic resistance is
usually induced after failure. Quadruple therapy has been used as a salvage
regimen in failed cases but it is also the most complicated regimen. Several new
agents are being studied including a single capsule that contains bismuth,
metronidazole, and tetracycline.
PMID- 17031147
TI - Gastrointestinal infections in children.
AB - Gastrointestinal infections in children are a major cause of morbidity and
mortality worldwide. Children living in developing countries are particularly
susceptible to infectious diarrhea because of poor standards of hygiene and
sanitation. Although the magnitude of diarrheal illnesses in developed countries
is less, costly hospital admissions are still frequent. The causal agent of
infectious diarrhea is most frequently related to age, geographical location,
lifestyle habits, use of antibiotics, associated medical conditions, social
circumstances, and degree of immune competence. In this article we present some
of the most important articles published in the field during the last year. The
role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer
disease has been shown in adults and children. Information about the natural
history of H. pylori, symptomatology, and diagnostic therapeutic approaches for
children are being generated constantly; we discuss some of the most relevant
information in this review.
PMID- 17031148
TI - Gastrointestinal infections in the immunocompromised host.
AB - The gastrointestinal tract is a common site of infection in the opportunistic
host. Pathogens range from highly virulent organisms, which infect people with
well functioning immune systems as well as people with poorly functioning immune
systems, to opportunistic organisms, which infect only those with impaired immune
systems. Viruses, bacteria, fungi, and protozoa lead to disease that can be
especially severe, debilitating, and difficult to treat in the immunocompromised
host. Yet in this era of highly active antiretroviral therapy for HIV-infected
patients and strategies to reduce immunosuppression in transplant and oncology
patients, appropriate diagnostic tests and treatment can both improve the quality
of life and decrease mortality. In this article, I review the changing
pathogenesis, epidemiology, clinical presentation, diagnosis, and treatment of
gastrointestinal infections in the immunocompromised host.
PMID- 17031149
TI - Treatment of gastrointestinal infections.
AB - Studies aimed at improving treatment strategies for patients with acute diarrhea
have included the clinical testing of modifications to the standard oral
rehydration solution. A malabsorbed carbohydrate has been found to improve
resuscitation, probably through the recruitment of colonic absorptive capacity. A
reduced osmolarity solution is safe in adults and as effective as the standard
solution. For non-nursing infants, increasing the frequency of feeding with
reduced volume results in comparable total caloric intake and diminishes the risk
of prolonged diarrhea. Increasing resistance of important enteric pathogens to
inexpensive and newer antibiotics continues to be a concern. Reports from Asia of
decreased Salmonella typhi resistance to chloramphenicol, attributed to
restricted antibiotic usage, may indicate a reversal of the usual trend. A
strategy to block the action of shiga toxins in the gut through the use of
recombinant bacteria has shown promise in a mouse model. A small but well
designed study supported the use of either norfloxacin or amoxicillin-clavulanic
acid in the treatment of small bowel overgrowth syndrome. Studies exploring
passive immunity strategies for the treatment of Escherichia coli,
Cryptosporidium, and Candida infections have reported variable levels of success.
PMID- 17031150
TI - Molecular-phylogenetic analyses of human gastrointestinal microbiota.
AB - Molecular-phylogenetic methods have revolutionized the analysis of complex
microbial communities. Polymerase chain reaction amplification and phylogenetic
analysis of small-subunit ribosomal RNA gene sequences allow microbes to be
identified objectively, even in the absence of cultivation. Furthermore, the
sequence information obtained by these means can be used to design sequence-based
tools for identifying, tracking, and diagnosing the presence of microbes in
complex samples. In this article, we summarize this approach and review its
application to the study of the human gastrointestinal microbiota. Although just
beginning, molecular-phylogenetic surveys of human gut microbes have revealed
that most microbes identified in the gastrointestinal tract represent novel,
previously undescribed species. A full description of the microbial constituents
of the human gut will set the groundwork for interpreting how the
gastrointestinal microbiota influence the health of the host.
PMID- 17031151
TI - The role of probiotics in the treatment of intestinal infections and
inflammation.
AB - Clinical studies have established that certain probiotics are useful in a variety
of intestinal disorders, including viral diarrhea, antibiotic-associated
diarrhea, Clostridium difficile-associated diarrhea, and traveler's diarrhea.
Evolving data suggest that probiotics might be useful in the control of
inflammatory diseases, treatment and prevention of allergic diseases, cancer
prevention, and stimulation of the immune system, which may result in the
reduction in respiratory disease. A review of current data regarding the most
common probiotics is presented. It is important that probiotic use be directed by
well-designed, placebo-controlled clinical studies published in peer-reviewed
journals.
PMID- 17031153
TI - Nonsteroidal antiinflammatory drugs, cyclooxygenase-2, and colorectal cancer
prevention.
AB - Colorectal cancer is the second leading cause of cancer deaths in the United
States. Despite proven screening strategies, less than 40% of eligible Americans
undergo appropriate screening for colorectal cancer. Research evaluating the
underlying defects responsible for hereditary nonpolyposis colorectal cancer and
familial adenomatous polyposis has provided insight into some of the molecular
mechanisms responsible for familial and sporadic colorectal cancer. The signaling
pathways involved in the development of colorectal cancer may provide effective
targets for prevention and treatment. These targets include cyclooxygenase-2,
peroxisome proliferator activated receptor- delta, peroxisome proliferator
activated receptor- gamma, transforming growth factor- beta receptors, and the
inducible-nitric oxide synthase.
PMID- 17031154
TI - The role of vitamin D in normal and pathologic processes in the colon.
AB - Vitamin D(3) metabolites and analogues have recently been shown to play an
important role in the regulation of a number of important cellular processes,
including proliferation, differentiation, and apoptosis, in addition to their
established roles in mineral homeostasis. The actions of these secosteroids
involve both rapid, nongenomic effects and genomic effects; the latter mediated
via the vitamin D receptor and other transcription factors. Their effects have
been described in a variety of cell types, including normal and malignant
colonocytes. This article summarizes the rapid and genomic actions of vitamin
D(3) metabolites and analogues on normal and pathologic processes in the colon,
with particular emphasis on the potential of these secosteroids to prevent colon
cancer.
PMID- 17031155
TI - Virtual colonoscopy: a new tool for colorectal cancer screening.
AB - Virtual colonoscopy or computed-tomography colonography is a promising new method
for colorectal cancer screening. Helical computed tomography is used to generate
high-resolution, two-dimensional axial images of the abdomen and pelvis. Three
dimensional images of the colon simulating those obtained with conventional
colonoscopy can be reconstructed from the data obtained. Favorable attributes of
virtual colonoscopy include its safety, high patient acceptance, and ability to
provide a full structural evaluation of the entire colon. Multiple studies of
virtual colonoscopy have been published in the literature in the past year
regarding technique, image display, image reconstruction, clinical trial results,
and feasibility as a screening tool. This manuscript will review the various
studies in each of these areas.
PMID- 17031156
TI - The role of radiation therapy in the adjuvant treatment of rectal cancer.
AB - There have been several advances in the treatment of rectal cancer in the past 20
years. The recognition that surgical therapy alone leads to a local failure rate
of 15 to 50% in stages II and III has led to the use of adjuvant radiation
therapy. Multiple prospective, randomized trials conducted by multi-institutional
cooperative groups have resulted in the use of adjuvant combined modality therapy
using radiation therapy and 5-fluorouracil chemotherapy. Some of the trials fine
tuned the sequencing and dose of radiation and chemotherapy to maximize efficacy
and minimize toxicity. The advent of accurate endorectal ultrasound and MRI
staging has allowed the use of preoperative therapy without the unnecessary
treatment of patients with early stage. This has resulted in greater sphincter
preservation and fewer complications. The optimal sequencing of adjuvant therapy
has yet to be found.
PMID- 17031157
TI - Enteric nervous system, serotonin, and the irritable bowel syndrome.
AB - Intestinal motility, secretion, and blood flow are controlled and integrated by
the enteric nervous system (ENS). The ENS is like a "brain-in-the-gut," with many
of the neurophysiologic properties of the central nervous system. Serotonin is a
neurotransmitter at synapses in the microcircuits of the ENS. Serotonin is also
released from enterochromaffin cells and inflammatory/immune cells to act at
serotonergic receptors on neurons of the ENS. Four important actions are (1) fast
and (2) slow excitation of enteric neurons, (3) presynaptic inhibition of
neurotransmitter release at synapses in ENS microcircuits, and (4) excitation of
intestinal sensory afferent fibers. Fast excitation and stimulation of sensory
afferents are mediated by 5-HT(3) serotonergic receptors and slow excitation by 5
HT(1P) receptors. Presynaptic inhibitory receptors are not conclusively defined.
The efficacy of a new 5-HT(3) receptor blocking drug in the treatment of the
diarrhea-predominant form of the irritable bowel syndrome in women suggests the
importance of this receptor subtype in the mediation of neurogenic secretory
diarrhea, motility abnormality, and abdominal pain and discomfort.
PMID- 17031158
TI - Current world literature.
PMID- 17031160
TI - Pathology of the liver.
AB - Traditional anatomic pathology studies and molecular investigations both
contributed to the breadth of current information in the field of liver pathology
this year. Techniques such as reverse transcription polymerase chain reaction can
identify recurrence of hepatitis C virus infection in the liver as early as 5
days after transplantation. Chronic rejection after transplantation may be
characterized not only by ductopenia but also by loss of portal tract hepatic
artery branches. There are many diseases of small bile ducts in adults, and
idiopathic adulthood ductopenia has been identified in extended family members.
Adverse reactions to drugs may precipitate their removal from the pharmacopoeia,
such as the many cases reported of severe bridging and submassive necrosis due to
troglitazone (a thiazolidinedione antidiabetic agent). Several publications
highlighted the association of hepatitis C virus infection with
lymphoproliferative diseases and, newly, with cholangiocarcinoma.
PMID- 17031161
TI - Cellular and molecular biology of the liver.
AB - Recently, several lines of investigation focused on basic mechanisms governing
cellular and molecular aspects of liver biology have intersected at the study of
the hepatic stem cell. Despite years of study, the very question of the existence
of the hepatic stem cell has yet to be unequivocally established. A second field
of investigation into the cellular and molecular aspects of liver biology is
aimed at liver-directed gene therapy in which several new vehicles have been
devised to mediate gene transfer. Gene therapy is no longer thought of in the
limited framework of a means to correct inherited disorders; it is now expanding
into new therapeutic applications. A third major area of investigation includes
studies of mechanisms that regulate membrane protein traffic necessary to
maintain the integrity of differentiated liver cell function. In this review,
some of the most recent advances and applications in these three areas are
highlighted, and, where appropriate, points of interaction and potential
therapeutic importance are emphasized.
PMID- 17031162
TI - Alcoholic liver disease.
AB - Research has substantiated the role of several mechanisms responsible for alcohol
induced hepatotoxicity. These mechanisms include: oxidative stress and lipid
peroxidation; immunogenic processes initiated by formation of protein adducts of
acetaldehyde, other aldehydes and 1-hydroxyethyl radicals; and activation of
Kupffer cells by endotoxin and subsequent cascade of events that involved
cytokines, chemokines, and adhesion molecules. Increasing evidence implicates
enhanced intestinal permeability caused by alcohol ingestion as the culprit that
leads to endotoxemia. While oxidative stress is important, the principal source
of reactive oxygen species that causes alcohol-induced liver injury is hotly
debated. Potential sources may include cytochrome P450IIE1, activated Kupffer
cells, and mitochondrial electron transfer chain. Apoptosis is likely an
important pathway that culminates in hepatocyte cell death. Abstinence,
corticosteroids, and enteral nutrition remain the cornerstones in the treatment
of alcoholic hepatitis. The efficacies of medications such as S
adenosylmethionine and pentoxifylline will need further confirmation by
additional randomized trials before they can be recommended as standard therapies
for alcoholic hepatitis.
PMID- 17031163
TI - Metabolic liver disease.
AB - The discovery of novel metabolic pathways and the genetic basis for diseases of
the liver continues to yield new insights into the pathogenesis of inherited
metabolic diseases of the liver, whereas the application of new technologies to
their treatment continues to advance therapeutic options. This review of selected
articles covers a wide range of subjects, from the identification of novel
proteins and transport pathways to disease diagnosis and treatment of acute liver
failure. Four selected topics, Wilson disease, hemochromatosis and iron overload
disorders, alpha-1 antitrypsin disease, and exciting new therapeutic options for
lysosomal storage diseases are the focus of this review.
PMID- 17031164
TI - Drug-induced liver disease.
AB - This year's review is divided into several sections: the first describes drug
withdrawals and new general reviews of drug-induced liver disease (DILD),
including a review of a classification of drug injury. We review agents newly
described as causing DILD, and new reports of DILD from established agents
appearing in the year 2000. New aspects regarding the treatment of acetaminophen
toxicity are included, and in the final section we deal with prevention of DILD
as well as issues surrounding the use of potentially hepatotoxic medications in
patients with underlying chronic disease.
PMID- 17031165
TI - Cholestatic syndromes.
AB - New insights into the regulation of hepatobiliary transport proteins have
provided the basis for a better understanding of the pathogenesis of cholestatic
liver diseases. Mutations of transporter genes can cause hereditary cholestatic
syndromes, the study of which has shed much light on the basic mechanisms of bile
secretion and cholestasis. Important new studies have been published about the
pathogenesis, clinical features, and treatment of primary biliary cirrhosis,
primary sclerosing cholangitis, cholestasis of pregnancy, total parenteral
nutrition-induced cholestasis, and drug-induced cholestasis.
PMID- 17031166
TI - Hepatobiliary infections.
AB - The major hepatobiliary infections (excluding the viral hepatitides) include
amebic and pyogenic liver abscess and cholangitis. Little new information has
been published in the area of cholangitis during the last several years. In
contrast, the clinical presentation and management of liver abscess have evolved
considerably, not only in the last several years but also during a more extended
period spanning the last two decades. In the United States, amebic liver abscess
occurs largely in individuals from endemic areas or in those traveling to endemic
areas. Recent data suggest that patients with human immunodeficiency virus (HIV)
infection are at an increased incidence of amebic liver abscess. New serologic
tests and molecular techniques are being added to the diagnostic armamentarium
for amebic liver abscess. In most cases, amebic liver abscess is associated with
an excellent prognosis (up to 100% survival) if properly managed. Pyogenic liver
abscess, although commonly occurring in patients with known biliary tract
disease, is often cryptogenic in origin (ie, no clear causal factor can be
identified) or often is caused by underlying medical disorders. An emerging
population of patients with pyogenic liver abscess includes those with
complications of aggressive interventions (hepatic chemoembolization,
cryoablation, liver transplantation). Pyogenic liver abscess was predominantly
managed by surgical methods up until the early 1980s, but almost entirely has
changed to being managed by interventional techniques; in 2000, this trend has
continued. In contrast to amebic liver abscess, pyogenic liver abscess is
associated with greater morbidity and mortality, ostensibly caused by the
severity of the underlying disease in many patients. However, it should be
emphasized that the prognosis of patients with pyogenic liver abscess, who do not
have underlying comorbid conditions, is excellent.
PMID- 17031167
TI - Viral hepatitis.
AB - Viral hepatitis constitutes the most common entity seen in hepatology practice.
Hepatitis A vaccination is recommended for patients with chronic hepatitis. Both
lamivudine and interferon are established therapies against chronic hepatitis B,
with other treatments not equally effective. Adefovir dipivoxil is a promising
new treatment for lamivudine-resistant hepatitis B mutants. Lamivudine and
hepatitis B immunoglobulin are effective in preventing recurrence of hepatitis B
after transplantation. The combination of interferon and ribavirin has been shown
to be effective for treatment of hepatitis C. Studies support the antiviral,
antifibrotic, and antineoplastic effect of interferon therapy. Recurrence of
hepatitis C after transplantation has been associated with more rapid progression
to cirrhosis. Other major advances in the field of viral hepatitis during the
past year are highlighted.
PMID- 17031168
TI - Autoimmune liver disease.
AB - Autoimmune hepatitis in children may be associated with sclerosing cholangitis in
the absence of inflammatory bowel disease. Wilson disease can have clinical and
laboratory features that resemble autoimmune hepatitis, and it may respond
initially to corticosteroids. Soluble HLA-DR antigens reflect clinical activity,
and they may be useful markers of treatment response. Polymorphisms of the
cytotoxic T lymphocyte antigen-4 gene may synergize with other autoimmune
promoters or HLA risk factors to increase susceptibility and alter disease
expression. DRB1*1301 distinguishes Argentine children from Argentine adults and
identifies a unique subgroup. Antibodies to soluble liver antigen/liver-pancreas
do not characterize a separate clinical entity. Their target antigen has been
isolated, and it shares homologies with a selenocysteine-specific protecting
factor (tRNP((Ser)Sec)). CYP2D6 is expressed on the hepatocyte surface, and it
can be targeted by antibodies in autoimmune hepatitis and chronic hepatitis C.
Perinuclear antineutrophil cytoplasmic antibodies lack sensitivity and
specificity for autoimmune hepatitis, and they have diverse antigen
specificities. Activation-induced cell death may be impaired in autoimmune
hepatitis, and, in contrast to budesonide, mycophenolate mofetil has been
effective in a small study of problematic patients.
PMID- 17031169
TI - Hepatocellular carcinoma.
AB - The number of papers published regarding hepatocellular carcinoma between 1999
and 2001 increased from previous years. This year a study confirmed the increase
in incidence in the United States. Also, several studies established for the
first time that tobacco smoking was a risk factor for the development of this
tumor. Several studies established that the process of angiogenesis is critical
for the development of hepatocellular carcinoma, and one paper indicated that
inhibiting this process might lead to possible treatment of this tumor. Resection
was compared with liver transplantation for the first time in two studies. It was
shown that transplantation offered the overall best long-term option, but in a
certain group of patients without portal hypertension and well-preserved liver
function resection is the best option.
PMID- 17031170
TI - Portal hypertension.
AB - Portal hypertension is the main complication of cirrhosis and is responsible for
its most common complications: variceal hemorrhage, ascites, and portosystemic
encephalopathy. Portal hypertension is the result of increased intrahepatic
resistance and increased portal venous inflow, which in turn is the result of
splanchnic vasodilatation. Vasodilatation (splanchnic and systemic) and
hyperdynamic circulation are hemodynamic abnormalities typical of cirrhosis and
portal hypertension. Gastroesophageal varices result almost solely from portal
hypertension, although the hyperdynamic circulation contributes to variceal
growth and hemorrhage. Ascites results from sinusoidal hypertension and sodium
retention, which is, in turn, secondary to vasodilatation and activation of
neurohumoral systems. The hepatorenal syndrome represents the result of extreme
vasodilatation with an extreme decrease in effective blood volume that leads to
maximal activation of vasoconstrictive systems, renal vasoconstriction, and renal
failure. Spontaneous bacterial peritonitis is a potentially lethal infection of
ascites that occurs in the absence of a local source of infection. Portosystemic
encephalopathy is a consequence of both portal hypertension (shunting of blood
through portosystemic collaterals) and hepatic insufficiency that result in the
accumulation of neurotoxins in the brain. This paper reviews the recent advances
in the pathophysiology and management of the complications of portal
hypertension.
PMID- 17031171
TI - Acute liver failure.
AB - Worldwide, viral hepatitis is the leading cause of acute liver failure, whereas
acetaminophen hepatotoxicity is the most commonly identified cause in Western
countries. Restricting the quantity of acetaminophen tablets dispensed has been
shown to reduce morbidity and mortality in countries with a high incidence of
acetaminophen overdose. Troglitazone and bromfenac are two recently approved
medications that were withdrawn from the market due to an unacceptably high
incidence of severe hepatotoxicity. In addition, trovafloxacin, nefazodone, and
ritonavir were reported to be associated with severe hepatitis and acute liver
failure. Moderate hypothermia is a simple and potentially effective means of
reducing intracranial pressure in patients with acute liver failure and cerebral
edema. However, controlled clinical trials are needed to determine proper patient
selection and optimize treatment. Extracorporeal bioartificial liver support
devices remain an exciting but as yet unproven means of supporting acute liver
failure patients with advanced encephalopathy. Living donor liver transplantation
has recently been reported for adults and children with acute liver failure.
However, ethical concerns regarding donor safety and the ability to obtain
informed consent without coercion have been raised. Lastly, advances in the
identification and isolation of pluripotent liver stem cells in human bone marrow
provides hope for a simple and effective means of enhancing native liver
regeneration.
PMID- 17031172
TI - Liver transplantation.
AB - Continued discussion over organ allocation and distribution remained a focal
point in the field of liver transplantation in the year 2000. Despite the ongoing
debate, no significant changes were implemented in the current allocation system.
By far, the most widely discussed topic in liver transplantation this year was
live donor adult-to-adult liver transplantation. Several authors reported on
their initial experience, with both recipient and donor outcomes appearing
excellent. As the number of transplant centers performing this procedure
increases we look forward to further studies regarding the safety and long-term
outcome of this innovative procedure. Studies on viral hepatitis after liver
transplantation again focused on the problem of recurrent hepatitis B and
hepatitis C. Several small studies found benefit in patients with hepatitis B
treated with intramuscular hepatitis B immunoglobulin and lamivudine after
transplantation. Although breakthrough replication remains a problem in some
patients, these studies offer hope that combination therapy for hepatitis B may
provide improved long-term graft survival in these patients. In patients with
hepatitis C, several studies focused on identifying risk factors to predict graft
recurrence of the virus after liver transplantation. Both cellular rejection and
level of viral replication may be important predictors of recurrent hepatitis C
virus in the graft. Early treatment reports using interferon and ribavirin
suggest that some patients may have a viral response during therapy; however, it
is short lived, and tolerance of medication is difficult. Certainly, we look
forward to further studies looking at means of prevention and treatment of viral
hepatitis in patients undergoing liver transplantation.
PMID- 17031173
TI - Bibliography. Current world literature. Inflammatory bowel disease.
PMID- 17031175
TI - Mechanisms of tissue damage in inflammatory bowel disease.
AB - Crohn disease and ulcerative colitis are caused by an excessive immune
inflammatory reaction in the intestinal wall. Analysis of the types of immune
response ongoing in the inflamed intestine has revealed that in Crohn disease
there is predominantly a T helper cell type 1 response, with exaggerated
production of interleukin (IL)-12 and interferon-gamma, whereas in ulcerative
colitis the lesion seems to be more of an antibody-mediated hypersensitivity
reaction. Despite these differences, downstream inflammatory events are probably
similar in both conditions. In both Crohn disease and ulcerative colitis there is
an increased synthesis of proinflammatory cytokines, including IL-1beta, IL-6, IL
8, IL-16, and tumor necrosis factor-alpha accompanying the influx of nonspecific
inflammatory cells into the mucosa. These cytokines contribute to the tissue
damage either directly or indirectly by enhancing the production of matrix
metalloproteinases and growth factors, which produce ulceration as well as
mucosal repair.
PMID- 17031176
TI - Mechanisms of tissue protection and repair in inflammatory bowel disease.
AB - Investigators have increasingly appreciated the importance of the breakdown of
the epithelial barrier in the pathogenesis of inflammatory bowel disease.
Epithelial cells secrete trefoil factors, heat shock proteins, and secretory
leukocyte proteinase inhibitors that protect the integrity of the epithelial
barrier. Other agents, including growth factors, regulate the repair of the
epithelium after injury has occurred. Drugs that would either enhance protection
of barrier function from injury or accelerate repair after injury would have
therapeutic potential in inflammatory bowel disease.
PMID- 17031177
TI - Intestinal fibrosis in human and experimental inflammatory bowel disease.
AB - Fibrosis is a serious complication of Crohn disease for which there is no
effective therapy. It is unclear why fibrosis, particularly fibrosis of the
mucosal layer, develops in Crohn disease and not in ulcerative colitis. Smooth
muscle cells, subepithelial myofibroblasts, and fibroblasts have traditionally
been considered mediators of fibrosis, but new information points to a role of
interstitial cells of Cajal and mast cells. Recent evidence about the role of
each of these cell types in fibrosis in Crohn disease or other inflammatory bowel
diseases is described. Hypothetical models to describe how altered function of
these cells could underlie fibrosis of the mucosa or submucosal layers are
presented. Fibrosis is not well characterized in any animal model of inflammatory
bowel disease. The merits of several animal models for defining the mechanisms of
inflammation-induced intestinal fibrosis are reviewed.
PMID- 17031178
TI - Intestinal microflora in human and experimental inflammatory bowel disease.
AB - Commensal luminal bacteria stimulate protective or tolerogenic mucosal immune
responses in normal (ie, resistant) hosts and detrimental responses, which result
in chronic intestinal inflammation, in genetically susceptible hosts. Enteric
pathogens appear to be important in the initiation and reactivation of human
inflammatory bowel disease, and may be responsible for chronic inflammation in at
least a subset of patients with inflammatory bowel diseases. Individual
components of the commensal flora have variable abilities to induce inflammatory
and protective immune responses; these preferential immune responses to
individual bacterial species may be unique to each host's genetic background.
Analogous to the balance between pro- and antiinflammatory cytokines and T-cell
subsets, the ratio between protective (ie, probiotic) and aggressive commensal
bacteria may determine whether there is mucosal homeostasis or chronic, relapsing
intestinal inflammation. Therapeutic alteration of the luminal microenvironment
by probiotic, prebiotic, and molecular strategies offers great promise for
nontoxic treatment of inflammatory bowel disease.
PMID- 17031179
TI - Probiotics and antibiotics in inflammatory bowel disease.
AB - Many experimental and clinical observations suggest a potential role for
intestinal microflora in the pathogenesis of inflammatory bowel disease.
Manipulation of the luminal content using antibiotics and/or probiotics may
represent a potentially effective therapeutic option. Results of antibiotic
treatment in inflammatory bowel disease are controversial, but this approach is
frequently and successfully adopted in clinical practice. Recent data support the
potential therapeutic role of probiotics in inflammatory bowel disease. In
particular, a highly concentrated probiotic preparation was shown to be superior
to placebo both on the prevention of pouchitis onset and of chronic pouchitis
relapse. Its role in the maintenance treatment of ulcerative colitis and Crohn
disease needs to be further assessed by large, double-blind, controlled trials.
Future research needs to be focused on obtaining more precise information on the
enteric microflora and the mechanisms of action of probiotics.
PMID- 17031180
TI - Medical management of inflammatory bowel disease: old and new perspectives.
AB - The treatment of inflammatory bowel disease is a continually evolving area and a
major focus of the current literature in gastroenterology. As further information
is gained in the areas of etiology, pathophysiology, and natural history of the
disease, new agents are developed, and management strategies are revised. The
contribution of this year's clinically based literature is reviewed in this
summary and incorporated into specific management strategies.
PMID- 17031181
TI - Nutrition in inflammatory bowel disease: impact on disease and therapy.
AB - Nutritional derangements are frequent in inflammatory bowel disease. In the last
year, significant work was published examining the mechanisms of impaired food
intake in animal models of inflammatory bowel disease, which allow a better
understanding of these processes. These data have shed new light on the relative
role of underfeeding and inflammation on the growth retardation associated with
intestinal inflammation. Other studies have provided further information on the
risk factors and predictive biomarkers of bone loss in patients with inflammatory
bowel disease. The potential role of enteral nutrition as primary therapy for
Crohn disease is particularly addressed in the present review. Recent
contributions emphasized the special importance of this therapeutic modality in
pediatric patients, but the possible mechanisms for such therapeutic effect are
still not well understood. Other nutrients may have a therapeutic potential in
inflammatory bowel disease. In particular, recent data on the in vivo
antiinflammatory action of butyrate merit special mention. Finally, novel
nutritional therapeutic strategies for inflammatory bowel disease, such as
transforming growth factor-beta2-enriched enteral feeding or hydrothermally
processed cereals, have recently been explored.
PMID- 17031182
TI - Pediatric inflammatory bowel disease: clinical and therapeutic aspects.
AB - Epidemiologic data suggest that the incidences of pediatric ulcerative colitis
and Crohn disease continue to evolve with geographic variations. One study
suggests that children with autism have a unique inflammatory bowel disorder that
is associated with gastrointestinal symptoms. The appropriate use of new
diagnostic tests and novel treatments for inflammatory bowel disease (IBD) needs
to be clarified in the pediatric population. Because of concerns regarding
sensitivity and specificity, serologic markers measuring anti-Saccharomyces
cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies
cannot yet replace conventional diagnostic testing for screening or diagnosis of
pediatric IBD. Large, prospective, pediatric population-based studies still need
to be performed to ascertain their use as a noninvasive screening tool. Genetic
studies using thiopurine methyl transferase and measurement of 6-mercaptopurine
metabolites appear to be valuable for management of pediatric patients with IBD,
in assisting clinicians in optimizing therapeutic response to 6-mercaptopurine,
and in identifying individuals at increased risk for drug-induced toxicity. Newer
immunomodulatory agents also are being explored in pediatric IBD. Open pilot
trials of infliximab (Remicade; Centocor, Malvern, PA) for the treatment of
children with Crohn disease that does not respond to conventional management have
demonstrated short-term efficacy and safety. Trials of tacrolimus for treatment
of fulminant colitis in children have been disappointing.
PMID- 17031184
TI - Gastroesophageal reflux disease.
AB - Gastroesophageal reflux disease (GERD) is a chronic disorder that affects
millions of people worldwide and has the potential to lead to serious
consequences, including cancer of the esophagus. It for this reason that there is
such intense interest in the topic, this emphasized by the identification of some
341 articles published in the English language in the year 2000 alone. The
present report highlights the results of a number of studies that either increase
our understanding of the condition or raise important issues about its diagnosis
and treatment. Included in the areas covered are (1) the role of genetics in
GERD; (2) the mechanism for transient lower esophageal sphincter relaxations and
their association with hiatal hernias; (3) the role of Helicobacter pylori in
GERD and Barrett esophagus; (4) efficacy and safety of proton pump inhibitors in
GERD; and (5) the mechanism for chronic cough in patients with GERD, among
others.
PMID- 17031186
TI - Chest pain of esophageal origin.
AB - Chest pain of esophageal origin or noncardiac chest pain is reported by at least
a fifth of the general population. Recent literature focused on further
understanding mechanisms of chest pain in subset of patients with functional
chest pain of presumed esophageal origin. Studies have demonstrated concurrent
visceral and somatic pain hypersensitivity, and amplified secondary allodynia, in
patients with noncardiac chest pain (NCCP), suggesting central sensitization.
Other studies have demonstrated abnormal cerebral processing of intraesophageal
stimuli. However, gastroesophageal reflux disease (GERD) has remained the most
common esophageal cause of NCCP. The introduction of the proton pump inhibitor
test, a highly sensitive and cost-effective diagnostic strategy, simplified our
diagnostic approach toward patients with GERD-related NCCP. For patients with
positive proton-pump-inhibitor test results, long-term treatment with antireflux
medication is warranted. For patients with non-GERD-related NCCP, pain modulators
remain the cornerstone of therapy.
PMID- 17031185
TI - Esophageal motor disorders.
AB - Esophageal motor function remains of investigative and clinical interest because
of its relevance to symptoms and its relation to the occurrence and management of
gastroesophageal reflux disease. Refinement in diagnostic methods continues to
occur, and improved tests for identifying the nature or severity of motor
disturbances in both the proximal and distal esophageal regions are now well
described. Controversy concerning the management of achalasia, the best
understood distal motor disorder, is resolving as the benefits and disadvantages
of available treatment options are becoming recognized. The relation of
esophageal motor dysfunction to outcomes from antireflux surgery remains
incompletely understood.
PMID- 17031187
TI - Barrett esophagus.
AB - There continues to be great interest in Barrett esophagus, the premalignant
lesion for adenocarcinoma of the esophagus and the esophagogastric junction.
There were several publications this past year related to the epidemiology,
pathogenesis, new methods for detection, biomarkers for stratifying patients by
risk, and the treatment of patients with Barrett esophagus. Patients with
intestinal metaplasia in short lengths of columnar mucosa in the distal esophagus
(ie, short-segment Barrett esophagus) appear to be distinct from those with
intestinal metaplasia in the gastric cardia. The reported risk of cancer in
patients with Barrett esophagus is probably subject to publication bias, with
small series reporting a higher incidence of cancer. New methods for the
diagnosis and detection of intestinal metaplasia and dysplasia are being
evaluated and may, in future, help in obtaining more accurate screening and more
focused surveillance of patients with Barrett esophagus. The validation of
biomarkers may help us to risk stratify patients at high risk for cancer
development. Endoscopic mucosal resection appears to be a safe and effective
technique for the resection and accurate diagnosis of dysplastic or cancerous
areas within Barrett esophagus.
PMID- 17031188
TI - Endoscopic therapeutic esophageal interventions.
AB - Despite numerous advances in the chemotherapeutic, radiotherapeutic, and surgical
treatment of esophageal cancer, most patients require some type of endoscopic
palliation for dysphagia during the course of their illness. Numerous modalities
exist, including thermal ablation with neodymium:yttrium-aluminum-garnet laser,
argon plasma coagulation, electrocautery, nonthermal ablation with alcohol
injection or photodynamic therapy, or displacement of tumor with endoscopically
placed stents. Each therapy carries with it a unique profile of efficacy and
complications. Some therapies may be more appropriate for certain tumor locations
and morphologies than others. During the past year, new studies have defined
these parameters further. However, it remains essential that the endoscopist have
both a thorough knowledge of these various modalities and an ability to chose
among them when undertaking endoscopic palliation of this difficult and rapidly
rising disease.
PMID- 17031189
TI - Esophageal cancer.
AB - Accurate pretherapy staging for esophageal cancer is important for stage-directed
therapy. Precise staging is also essential for quality control and ensuring the
validity of clinical trials. Endoscopic ultrasound is currently the best
technique in local regional staging. Various investigators have attempted to
overcome the problems of nontraversable lesions and restaging after neoadjuvant
therapy. Positron emission tomography scan was shown to be especially useful in
identifying distant metastases. Its more widespread use is likely to impact on
treatment strategies. Surgical resection remains the mainstay of treatment of
esophageal cancer. Improvement in immediate postoperative morbidity, mortality,
and long-term survival was shown by various reports to relate to experience and
volume. The concept of three-field dissection was further defined by illustrating
the importance of lymphadenectomy around the recurrent laryngeal nerves.
Multimodality treatments continue to receive attention. Several studies have
established the patterns of practice in the United States in treating esophageal
cancer. Chemoradiation programs are gaining a more important role and are widely
used, although their exact roles are uncertain. Closely related to this area of
research is the search of molecular markers of favorable response to such
therapies. Concerning palliative treatment for esophageal cancer, self-expanding
metallic stents have a definite role in patients with malignant dysphagia. Their
results and complications are reviewed. Lastly, quality-of-life issues have
assumed more importance in studies in oncology. Prospective quality-of-life data
should be evaluated in future studies on different treatment methods for this
deadly disease.
PMID- 17031190
TI - Surgery, radiotherapy, and chemotherapy for esophageal carcinoma.
AB - Over the last year, several interesting studies have been published on the
treatment of esophageal carcinoma. Surprisingly, none of them was a randomized
phase III trial. The debate on the necessary extent of a potentially curative
surgical resection is ongoing. After initially disappointing results, the
innovative technique of minimally invasive surgery draws new attention, but clear
advantages for the endoscopic approach are yet to emerge. An updated meta
analysis on the value of preoperative radiotherapy showed negative results. There
is a clear tendency toward combined-modality treatment, especially in patients
with more advanced disease. Some new chemotherapeutic agents showed promising
preliminary results (especially paclitaxel), whereas others were clearly
disappointing (eg, gemcitabine, topotecan). Concurrent chemoradiation as primary
treatment for proximal (cervical) tumors was remarkably effective.
PMID- 17031191
TI - Bibliography. Current world literature. Pancreas.
PMID- 17031193
TI - Receptor biology and signal transduction.
AB - This year has witnessed substantial advances in receptor biology and signal
transduction that are relevant to the function and regulation of the healthy
pancreas and to the pathogenesis and potential therapy of pancreatitis and
pancreatic carcinoma. There has been an expansion in the cast of pancreatic
regulatory molecules, now including protease-activated receptors, chemokines, and
chemokine receptors. There have been new insights into the cellular distribution
and signaling initiated at the classic pancreatic receptors. There have also been
dramatic advances in insights into the structure of G protein-coupled receptors,
with the first solution of a crystal structure of a member of this superfamily,
and into the molecular basis of ligand binding and activation of these important
molecules. This will clearly improve the opportunities for the rational design
and refinement of receptor-active drugs. In addition to these fundamental
advances, there has been renewed attention to the expression, function, and
regulation of receptors and signaling pathways in pancreatic cells present in the
setting of pancreatitis and pancreatic carcinoma. It is hoped that this will
contribute toward earlier diagnosis, more successful therapy, and new
chemopreventive strategies for these illnesses.
PMID- 17031194
TI - Neurohormonal control of exocrine pancreas.
AB - The exocrine pancreas is regulated by various hormonal factors derived from the
gut through hormone-hormonal and neurohormonal interactions. Physiologic stimuli
entering the upper small intestine elicit the release of intestinal hormones and
activate sensory reflex mechanisms from the intestinal mucosa to stimulate or
inhibit exocrine pancreatic secretion. In addition, the endocrine pancreas,
intrapancreatic nerves, and some extrapancreatic neural pathways, with or without
mediation by the vagus nerve, are known to participate in regulation of exocrine
pancreatic secretion. It has been established that two key intestinal hormones,
secretin and cholecystokinin (CCK), in physiologic doses, act through the vagal
afferent pathway and interact with each other as well as with other gut hormones.
The releases of these two hormones are mediated through the corresponding
releasing peptides. In the past few years, the roles of secretin- and CCK
releasing peptides have become more clearly defined. The participation of several
neurotransmitters and regulatory peptides in the regulation of exocrine
pancreatic secretion has also been established. In addition, neurotransmitters
and neuropeptides released from the central nervous system may participate in the
regulation of pancreatic secretion. It is conceivable that a few
neurotransmitters and neuropeptides are involved in each neural regulatory
pathway. However, their roles and sites of action in each pathway remain to be
determined.
PMID- 17031195
TI - Acute pancreatitis.
AB - The pathophysiologic concept of acute pancreatitis focuses on early events inside
acinar cells such as activation of trypsin. Despite significant progress in the
understanding of molecular events in experimental pancreatitis, knowledge of
these mechanisms has not yet been translated into therapeutic strategies useful
in humans. A single morphologic or laboratory marker reliably predicting the
individual course of acute pancreatitis still awaits discovery. The clinical
outcome of acute pancreatitis is dependent on the presence of necrosis and
systemic complications. The extent of the systemic inflammatory response to local
pancreatitis seems to be the rate-limiting step. Several mechanisms shed light on
the interconnectivity between intra-acinar protease activation and
immunoregulatory processes. Deciphering these cell biologic connections has
already had an impact on the clinical management of patients and the
identification of prognostic markers in human disease. However, further
investigations of pancreatic pathophysiology are needed to initiate novel
therapeutic strategies.
PMID- 17031196
TI - Chronic pancreatitis.
AB - An increasing number of novel mutations are associated with chronic pancreatitis.
Some cause a high-penetrance, autosomal dominant type of clinical picture (eg,
mutations at codons 29 and 122 of the cationic trypsinogen gene), whereas others
have a low penetrance or are frequent in the general population (eg, mutations in
Kazal type 1 [SPINK1] and in codons 16, 22, and 23 of the cationic trypsinogen
gene) and act as disease modifiers. The results of recent studies indicate that
smoking adversely affects the course and complications of chronic pancreatitis
(more frequent and faster rate of calcification and higher risk of development of
pancreatic cancer). Thus, regardless of the cause of chronic pancreatis, patients
with this condition should not smoke. Using current diagnostic criteria, the
accuracy of endoscopic ultrasound for the diagnosis of chronic pancreatitis is
not good. For example, 39% of dyspeptic persons without any other evidence of
chronic pancreatitis fulfilled the endoscopic ultrasound criteria for chronic
pancreatitis. Diabetes frequently occurs in chronic pancreatitis, but it is not
prevented or increased by pancreatic surgery. Islet cell autotransplantation
holds promise for the prevention of diabetes in patients requiring total
pancreatectomy if the pancreas is not extensively fibrotic. Splenic vein
occlusion is present in 7% of patients undergoing surgery for chronic
pancreatitis, but fewer than one fifth of these patients have variceal bleeding
before or after surgery.
PMID- 17031197
TI - TGFbeta-mediated signaling and transcriptional regulation in pancreatic
development and cancer.
AB - Transforming growth factor-beta (TGFbeta) plays a critical role in pancreatic
development and cell proliferation. Binding of TGFbeta to its membrane receptor
kinases activates the Smad signaling proteins, allowing them to translocate to
the nucleus and participate in the transcriptional control of TGFbeta target
genes. In addition, there is an increasing number of cellular mechanisms
affecting the final response of a cell to TGFbeta. This includes crosstalk with
other signaling pathways and the induction of TGFbeta early response genes, such
as the TGFbeta-inducible early response gene (TIEG) family of transcription
factors. Like the Smads, TIEGs behave as downstream effector proteins in TGFbeta
mediated pancreatic growth control. The discovery of the Smads and TIEGs has
provided new insights into TGFbeta-regulated functions. Their significance in
pancreatic development and cancer is discussed in this review.
PMID- 17031198
TI - Pancreatic surgery.
AB - Recent advances have been made in both laparoscopic and endoscopic techniques for
diagnosing and treating pancreatic neoplasms. These advances are reviewed. In
addition to the traditional methods of pancreatic resection (eg, standard Whipple
and pylorus-preserving Whipple), several other techniques have been described and
are discussed (eg, median pancreatectomy and extended pancreatectomy). The
morbidity and mortality rates of pancreatic operations have diminished, but
significant complications still occur (eg, delayed gastric emptying, pancreatic
fistula, and biliary strictures). These are discussed. In managing acute and
chronic pancreatitis, less invasive and more conservative approaches are being
advocated.
PMID- 17031199
TI - Biliary tract.
PMID- 17031200
TI - Biliary tract cancer.
AB - Advances in cellular and molecular biology of extrahepatic cholangiocarcinoma and
gallbladder adenocarcinoma are providing innovative means for the diagnosis and
treatment of biliary tract cancer. Similarly, refinements in noninvasive studies-
including helical computed tomography, magnetic resonance
cholangiopancreatography, and endoscopic ultrasonography--are enabling more
accurate diagnosis, staging, and treatment planning for these tumors. Complete
resection remains the only means for cure, and recent reports from major
hepatobiliary centers support aggressive wide resection for bile duct and
gallbladder cancer. Palliation of malignant strictures has improved with advanced
endoscopic techniques, newer polyurethane-covered stents, endoscopic microwave
coagulation therapy, and radiofrequency intraluminal endohyperthermia. The
preliminary data on such minimally invasive techniques suggest an improvement in
quality of life and survival for selected patients.
PMID- 17031201
TI - Sclerosing cholangitis.
AB - Primary sclerosing cholangitis is a chronic cholestatic disease that may have an
autoimmune basis. Most patients have a circulating antineutrophil cytoplasmic
antibody that appears to be targeted against a 50-kD nuclear envelope protein.
The clinical applications of this antibody have not yet been defined. Other
autoantibodies directed against antigens, such as cathepsin G, elastase, and
anticardiolipin, may also be detected in some patients. It is suggested that
primary sclerosing cholangitis may have a bacterial cause. Helicobacter gene
sequences have been detected in liver tissues in primary sclerosing cholangitis.
The role of Helicobacter spp and other bacteria in the etiopathogenesis of
primary sclerosing cholangitis remains to be determined. Primary sclerosing
cholangitis may overlap with autoimmune hepatitis in some cases, although the
real prevalence of this association remains to be determined. Many prognostic
models have been created, but they lack cross-validation, and their clinical
usefulness remains limited. Endoscopic retrograde cholangiography remains the
gold standard for diagnosis, but magnetic resonance imaging may be a viable
alternative in many cases. Clinical trials with cladibrine, pentoxifylline, and
budesonide have failed to demonstrate benefits. Orthotopic liver transplantation
remains the only effective treatment.
PMID- 17031202
TI - Gallstones.
AB - Gallstones are estimated to affect over 20 million people in the United States.
Recent studies have clarified the role of various dietary components in gallstone
disease. Also, insulin resistance has been demonstrated to be a risk factor for
gallstones. Other research has focused on the pathophysiology of gallstones and
on clarifying the underlying mechanisms of previously noted risk factors for
gallstones. New techniques for the noninvasive diagnosis of bile duct stones
continue to be developed and tested. These techniques include computed tomography
and magnetic resonance cholangiography. The impact and appropriateness of
laparoscopic cholecystectomy continue to debated, and studies point to both
overuse and underuse of this operation in the management of the disease.
PMID- 17031203
TI - Endoscopic management of biliary tract disease.
AB - New investigations, evaluation of controversial issues, and advances in
technology continue to shape the endoscopic management of biliary disorders. This
article discusses recent literature related to the diagnosis and therapy of
biliary tract disease. Specifically, the diagnosis and management of
choledocholithiasis, complications of biliary endoscopy and potential preventive
measures, roles for endosonography in the evaluation of biliary disease, and
endoscopic therapy of postoperative liver transplantation complications are
reviewed. Recent advances in biliary stents and the use of cholangioscopy in
biliary disorders are also assessed.
PMID- 17031204
TI - Liver involvement in childhood histiocytic syndromes.
AB - The histiocytic syndromes of childhood are disorders of the reticuloendothelial
system with variable clinical manifestations. Included among them are Langerhans
cell histiocytosis and hemophagocytic lymphohistiocytosis. This discussion will
be restricted to these two disorders. Liver disease in these conditions is
common. Langerhans cell histiocytosis is characterized by the abnormal clonal
proliferation of the macrophage-derived Langerhans cell. Liver involvement at
diagnosis has management and prognostic significance. In a subgroup of patients,
sclerosing cholangitis develops, which may lead to end-stage liver disease
requiring liver transplantation. Hemophagocytic lymphohistiocytosis is a disease
of abnormally activated macrophages that can involve multiple organ systems,
including the liver. Differentiation between this disorder and other causes of
pediatric liver disease is critical, because treatment strategies include
chemotherapy, immunosuppression, and frequently bone marrow transplantation.
PMID- 17031205
TI - Bibliography. Current world literature. Stomach and duodenum.
PMID- 17031207
TI - Gastric secretion.
AB - The influence of central and peripheral stimuli on gastric acid secretion is
mediated via activation of histaminergic, gastrinergic, and cholinergic pathways
coupled to intracellular second-messenger systems that determine the trafficking
and activity of H+ K+-ATPase, the proton pump of the parietal cell. Histamine,
released from enterochromaffin-like cells stimulates the parietal cell directly
via H-2 receptors coupled to generation of cAMP. Gastrin, acting via
cholecystokinin-2 receptors on enterochromaffin-like cells coupled to an increase
in intracellular calcium, stimulates the parietal cell indirectly by activating
histidine decarboxylase, releasing histamine, and inducing enterochromaffin-like
cell hypertrophy and hyperplasia. Acetylcholine, released from gastric
postganglionic intramural neurons, stimulates the parietal cell directly via M-3
receptors coupled to intracellular calcium release and calcium entry. The second
messenger systems activated in the parietal cell converge on H+ K+-ATPase that
catalyzes the exchange of luminal K+ for cytoplasmic H+ and is responsible for
gastric luminal acidification. The main inhibitor of acid secretion is
somatostatin which, acting via sst2 receptors, exerts a tonic inhibitory
influence on parietal, enterochromaffin-like, and gastrin cells. Acute infection
with Helicobacter pylori results in hypochlorhydria, whereas chronic infection
may be associated with either hypo- or hyperchlorhydria. Although prostaglandins
are thought to play a physiologic role in the regulation of acid secretion and
maintenance of gastric mucosal integrity, the precise roles of cyclooxygenase-1
and cyclooxygenase-2 in these processes still eludes us.
PMID- 17031208
TI - Gastroduodenal mucosal defense: coordination by a network of messengers and
mediators.
AB - Gastroduodenal mucosal defense is composed of structural features of the mucosa,
cellular monitors of pending or actual injury, and a web of effector cells that
protect the mucosa from damage and govern its recovery from injury. By virtue of
these systems, the gastroduodenal mucosa can cope with the harmful ingredients of
ingested food and the potentially deleterious effects of gastric acid and pepsin.
It is increasingly appreciated that a network of chemical messengers coordinates
the alarm, defensive, and healing mechanisms. This article highlights some of the
advances from the past year that have furthered our understanding of the
regulatory systems that govern gastroduodenal mucosal homeostasis. Particular
emphasis is given to control of the mucous and epithelial phospholipid barriers,
the mucosal microcirculation, and the epithelial, neural, immune, and
inflammatory mediators of the mucosal repair mechanisms.
PMID- 17031209
TI - The medical treatment of peptic ulcer disease.
AB - There is continued interest in the role of H. pylori in both uninvestigated and
non ulcer dyspepsia. The literature on this issue provided interesting, if at
times conflicting findings, leaving the clinician with little choice but to use
clinical judgment when dealing with these patients. On the Therapeutic front, a
"new" proton pump inhibitor, with impressive early efficacy data has been
launched, while an i.v. proton pump inhibitor formulation has reached a number of
markets. Emerging data on the use of potent acid suppression in especially GI
bleeding will almost certainly impact on the use of these agents. The
gastrointestinal effects of low dose aspirin use have received attention, while
the COX1-sparing agents have now started to impact on clinical practice. Two
large clinical outcomes studies with these agents have been published. Both
indicate at least some benefit, but raise interesting questions with regard to
the use of these agents in the clinical setting.
PMID- 17031210
TI - Nonsteroidal anti-inflammatory drug gastrointestinal toxicity.
AB - Toxic effects in the upper gastrointestinal tract, primarily complicated gastric
and intestinal ulcers, are the most common undesirable effects of the
nonsteroidal anti-inflammatory drugs. During the last several years, there have
been several advances, both in the laboratory and clinically, toward reducing
nonsteroidal anti-inflammatory drugs' gastrointestinal toxicity. Some of these
important developments are the delineation of mechanisms of nonsteroidal anti
inflammatory drug-induced gastrointestinal toxicity, identification of groups at
highest risk for development of nonsteroidal anti-inflammatory drug-induced
gastrointestinal complications, recognition of co-therapies that could reduce
nonsteroidal anti-inflammatory drug toxicity, and, most recently, development of
classes of nonsteroidal anti-inflammatory drugs with improved gastrointestinal
safety profiles. Many of these advances have occurred during the last year. This
review focuses on several of the important recent observations that have improved
understanding and safety of nonsteroidal anti-inflammatory drugs in the
gastrointestinal tract.
PMID- 17031211
TI - Gastroduodenal disorders in children.
AB - The North American Society for Pediatric Gastroenterology and Nutrition published
guidelines for the evaluation of children suspected of being infected with
Helicobacter pylori. The stool antigen test for H. pylori, which was recently
commercialized in the United States, was evaluated in two high-risk pediatric
populations. The results are encouraging but should be interpreted with caution.
A number of studies suggest that delayed gastric emptying may accompany a variety
of disorders, or may be a cause of vomiting. The outcome of children with
dyspeptic symptoms is described, and the results will be helpful in reassuring
anxious parents. Studies examining the development of H, K-adenosine
triphosphatase in infants and the role of enteric glial cells in infantile
hypertrophic pyloric stenosis are discussed. A study of neonates with allergic
gastroenteropathy suggests that this disorder may be more common in this age
group than generally thought.
PMID- 17031212
TI - Nonulcer dyspepsia.
AB - Therapy for nonulcer dyspepsia has largely been empiric because effective
therapeutic agents are sparse and therapeutic trials show inconsistent results.
The Cochrane collaboration has reviewed this matter and came to the conclusion
that prokinetics and acid-suppression therapy might have a significant, although
small, clinical benefit over placebo. Although the role of Helicobacter pylori in
nonulcer dyspepsia is still a matter of controversy, one meta-analysis suggests
that in H. pylori-positive dyspeptic patients, H. pylori eradication has a small
but significant therapeutic benefit over a therapy that does not eradicate H.
pylori. Other aspects of pathophysiology of nonulcer dyspepsia that have been
studied in the past year include visceral hyperalgesia and abnormal sleep
pattern. New studies have also investigated the clinical presentation of nonulcer
dyspepsia and the possible reasons why some patients never consult a doctor
whereas others do so frequently.
PMID- 17031213
TI - Interventional endoscopy.
AB - Interventional endoscopy is a general label given to endoscopic procedures used
to deal with a variety of gastrointestinal disorders. The interventional
endoscopic procedures of interest in this review are those used specifically with
gastric disorders. They include hemostasis, endoscopic ultrasound, endoscopic
mucosal resection, stenting, percutaneous endoscopic gastrostomy tube placement
and photodynamic laser therapy. Here, we review the latest data related to (a) a
number of general issues having an impact on this diverse group of procedures
(eg, such as proper patient selection criteria, consent in the era of open access
endoscopy, protocol for anticoagulation, and sedation); (b) the methodology and
outcomes of each of these unique procedures as they apply to the stomach; and (c)
some of the latest technologic advances and developments that will potentially
have an impact the future use of these procedures.
PMID- 17031214
TI - Gastric surgery.
AB - Significant advances in the role of gastric surgery in the management of disease
in the past year have focused on three broad areas: morbid obesity, gastric
cancer, and peptic ulcer disease. Although vertical banded gastroplasty and Roux
en-Y gastric bypass are the two procedures most commonly used in the United
States to induce weight loss in the morbidly obese patient, long-term follow-up
continues to support the durability of the gastric bypass in maintaining a
sustainable outcome with a minimum of complications. It is not surprising,
therefore, that increasing interest has accrued in simplifying this operation and
decreasing potential complications even further by employing laparoscopic
technology. In the area of gastric cancer, several reports have provided
important new information regarding its pathogenesis, factors influencing long
term survival, and strategies for management when diagnosed early. Finally, in
patients developing the complications of peptic ulcer disease (eg, obstruction
and perforation), conservative management has been emphasized over more radical
traditional approaches. This review highlights these advances.
PMID- 17031216
TI - Update on immunologic basis of celiac disease.
AB - During the past few years several seminal studies have greatly expanded our
knowledge on celiac disease pathogenesis. This review focuses on aspects that
have been most properly addressed and where substantial new information has been
gathered include. Topics covered include (a) the identification of T-cell
epitopes in gluten and the mechanisms of specific T-cell response in celiac
disease small intestine; (b) the mechanisms of induction of mucosal lesion; and
(c) the putative role of non-T-cell factors in driving mucosal response to
gliadin. After discussing a brief history of the "quest for the cause of celiac
disease," we examine the development of the typical celiac lesion (the crypt
hyperplastic mucosal atrophy) as it generally unfolds: the increased entry of
dietary antigens; the early changes, linked to specific components of the innate
immunity rather than to its adaptive branch; the most thoroughly investigated
subsequent response, involving a strong T-cell response and cytokines; and the
factors responsible for enterocytes' death. The emerging pattern is that of a
complex interaction of factors, although far from being completely understood,
but fascinating as it opens an incredible window of knowledge on an autoimmune
disorder whose environmental factor is known, whose autoantigen is known, whose
autoantibodies are known: a truly unique situation in medicine.
PMID- 17031217
TI - Gastrointestinal manifestations of primary immunodeficiencies.
AB - Congenital immunodeficiencies are relatively rare disorders that result in a
marked predisposition to infection and to a variety of gastrointestinal problems.
Increasingly recognized in both children and adults, accumulating worldwide
experience with these disorders reveals that the long-term prognosis is poor in
many cases, despite available treatments. This review highlights the past year's
advances concerning the molecular basis of several of these disorders, new
diagnostic considerations, and novel therapeutic approaches concerning their
gastrointestinal complications. The availability of molecular diagnostic tools
increases the options for earlier definitive treatments such as bone marrow
transplantation and somatic gene therapy.
PMID- 17031218
TI - Induction of mucosal immune responses by bacteria and bacterial components.
AB - Bacteria have well documented abilities to induce protective as well as
pathogenic mucosal immune responses, with the type of response dependent on the
genetically programmed balance of pro- and anti-inflammatory cytokines and T
lymphocyte subsets. Inflammatory bowel disease, especially Crohn disease and
periodontal disease, appear to be overly aggressive cellular immune responses to
some, but not all, normal resident bacteria. Recent evidence suggests that the
balance of protective (probiotic) and aggressive commensal luminal bacterial
species is an additional determinant of mucosal homeostasis (tolerance) versus
pathogenic immune responses (loss of tolerance) and that this balance can be
therapeutically manipulated. Mucosal pathogens elicit a characteristic profile of
cytokines from epithelial cells, including chemokines that recruit effector cells
to the site of invasion to clear the invading organism. The molecular mechanisms
of epithelial attachment and invasion of bacterial pathogens (eg, Salmonella,
Shigella, pathogenic Escherichia coli, and Yersinia) and the mechanisms of injury
induced by Clostridium difficile toxins and Helicobacter pylori are beginning to
be understood, as are the innate and cognate host immune responses to these
organisms, leading to novel means to effectively block bacterial injury and
induce protective immune responses through immunization.
PMID- 17031219
TI - Autoimmune hepatitis.
AB - Autoimmune liver disease encompasses several disorders (Table 1). Autoimmune
hepatitis (AIH) affects mainly women and is characterized histologically by a
portal tract mononuclear cell infiltrate disrupting the limiting plate and
invading the parenchyma ("interface hepatitis") and serologically by the presence
of autoantibodies and increased levels of immunoglobulin G (IgG), in the absence
of a known cause. AIH responds to immunosuppressive treatment. It can present
insidiously or as an acute hepatitis. The previously accepted requirement of 6
month duration of symptoms before diagnosis can be made has been abandoned and
treatment should be instituted as soon as the disease is diagnosed. In this
review, we concentrate on those reports that add to our knowledge in terms of
pathogenesis, differential diagnosis, treatment, and clinical course. Special
attention is given to overlap syndromes.
PMID- 17031220
TI - Role of innate immunity in cancer.
AB - Recently, much progress has been made in the field of tumor immunology. Much of
this work has focused on understanding and exploiting the innate immune response
to tumor cells. A novel human receptor-ligand system that mediates natural killer
(NK) and gammadelta T-cell killing of carcinoma cells has been identified, and
the functions of an equivalent system in mice are beginning to be explored. The
mechanisms of action of an innate tumoricidal cytokine, tumor necrosis factor
related apoptosis-inducing ligand (TRAIL), and of tumor cell resistance to it,
are emerging, as are the ways in which tumor cells evade the damaging effects of
IFN-gamma and of complement. Overcoming tumor cell resistance to innate immune
attack could prove to be a fruitful approach to cancer immunotherapy in the
clinic.
PMID- 17031221
TI - Mucosal barrier and immune mediators.
AB - The intestinal mucosa functions is an immunologic organ that plays a major role
in the development of oral tolerance and host-defense mechanisms. Antigens must
cross the intestinal epithelium in a controlled manner to interact with dendritic
antigen-presenting cells, because bacteria or their products are a primary risk
factor for the development of intestinal inflammation. Therefore, the regulation
of the intestinal epithelial cell barrier is central to the development of
intestinal immunity and inflammation, but the involved mechanisms are largely
unknown. Intestinal barrier function relies on the formation of tight junctions
at the apical contact areas of intestinal epithelial cells. Tight junctions have
a highly dynamic structure whose permeability, assembly, or disassembly can be
regulated by a variety of cellular and metabolic mediators, including cytokines,
which have major functions in the immune system. Immune modulators control tight
junction dependent intestinal barrier function during development, wound healing,
and pathologic processes such as cancer, infection, and chronic inflammation.
PMID- 17031223
TI - Campylobacter infection: small bowel and colon.
AB - The important contribution of Campylobacter infections to human enteric disease
is well established. Recent completion of the genomic sequence of a Campylobacter
jejuni strain has heralded a renaissance in the field of Campylobacter
pathogenesis research. With the application of novel, powerful technologies, our
understanding of how these organisms mediate disease is set to evolve rapidly
from its current, relatively neglected status.
PMID- 17031224
TI - Update on protozoan parasites of the intestine.
AB - The last year has seen new approaches to the diagnosis, treatment, and prevention
of protozoal infections of the gastrointestinal tract. Some of the news is not
good: new foodborne and swimming pool outbreaks of cyclosporiasis and
cryptosporidiosis, respectively, occurred in North America; paromomycin was shown
to be ineffective treatment for cryptosporidiosis; and these parasitic diseases
continued to have a worldwide impact on human health. On the bright side, there
were important advances in the understanding of the pathogenesis of
cryptosporidiosis and the diagnosis of amebiasis and giardiasis, and some new
leads on the treatment of cryptosporidiosis and refractory giardiasis. Finally,
evidence was found of acquired mucosal immunity to amebiasis in Bangladeshi
children, offering a guide for the development of an amebiasis vaccine. This
review is not intended to be comprehensive, but contains a variety of articles
that the authors hope will be of interest to the reader.
PMID- 17031225
TI - Helicobacter pylori infection: pathogenesis.
AB - Helicobacter pylori is known to be the cause of most gastric diseases, including
both peptic ulcer disease and gastric cancer. In the absence of eradication,
infection tends to be lifelong and the immune response ineffective in clearing
the bacteria. A number of groups have investigated whether the immune clearance
of infection can be achieved through a vaccination strategy, but to date, the
results have been inconclusive. In fact, in most cases of natural infection, the
host immune response leads to a chronic inflammation within the gastric mucosa
that actually promotes the development of atrophy and neoplasia. In most cases,
eradication of the organism leads to resolution of inflammation, which in many
instances can result in reduction in atrophy and gastric cancer risk. This
finding suggests that even at late stages, cancer progression is dependent, to a
large extent, on infection/immune response. Work from a number of laboratories
has led to the hypothesis that T-cells and the Th1 immune response, governed
largely by host genetic factors, are strongly associated with the H. pylori
mediated induction of atrophy and cancer. Interleukin-1beta appears to be a
particularly important cytokine that inhibits acid secretion and increases serum
gastrin levels, factors strongly associated with cancer induction. The induction
by H. pylori of cytokines and chemokines and growth-related genes is mediated by
the MAPK and NF-kappaB signaling pathway. Recent studies have shown that NF
kappaB is activated through a NF-kappaB-inducing kinase/p21-activated kinase 1
pathway. H. pylori can also promote cellular apoptosis through a number of
mechanisms, the most important of which is upregulation of the Fas/FasL pathway.
Finally, understanding of H. pylori pathogenesis has been broadened and deepened
by the application of genomics and proteomics to the organism.
PMID- 17031226
TI - Helicobacter pylori infection: treatment.
AB - Current standard treatment regimens for Helicobacter pylori infection provide
eradication rates 80 to 90%. These rates have been achieved with a variety of 1
week triple therapies using two antibiotics and an acid suppressant. Antibiotic
resistance, which may develop during failed treatment, is becoming increasingly
common and has led to studies of new regimens for primary therapy, and new
strategies for salvage of failed therapy. Other regimens have been designed and
tested with the aim of decreasing the cost of initial therapy or to improve
compliance, but abbreviated regimens have high incidence of failure and may add
to the problem of resistance. Increasing attention has been paid to the need for,
and timing of, the determination of antibiotic resistance of H. pylori isolates
either at the time of initial diagnosis or after treatment failure. New, simpler,
and noninvasive methods are offered for follow-up to determine if eradication has
been successful. Treatment regimens should be chosen based on local drug
susceptibility patterns and the availability of approved therapeutic agents in
each country. Established indications for testing for H. pylori and administering
therapy include active or inactive peptic ulcer disease, mucosa-associated
lymphoid tissue (MALT) lymphoma, as well as hyperplastic polyps, hyperplastic
gastropathy, postendoscopic resection for gastric malignancy, and acute H. pylori
gastritis. It is now largely accepted that noninvestigated dyspepsia is an
indication for testing for and treating H. pylori, but that dyspeptic symptoms
shown not to be associated with ulcer (nonulcer dyspepsia) do not now provide an
indication for testing. Controversial or unresolved indications for testing and
treating include planned use of chronic antisecretory therapy, planned use of
nonsteroidal anti-inflammatory drugs, and use as a general approach to the
prevention of gastric cancer.
PMID- 17031227
TI - Gastrointestinal infections in the immunocompromised host.
AB - Immunocompromised patients, including patients with AIDS, solid organ and bone
marrow transplant recipients, patients with leukemia and lymphoma, patients with
inherited immune deficiencies, and patients on immunosuppressive therapy for a
variety of disorders, are at risk for infections-particularly opportunistic
infections, which, by definition, do not infect the healthy host. All systems of
the body, including the gastrointestinal tract, are susceptible. The esophagus,
stomach, small intestine, and large intestine are sites of infection for viruses,
bacteria, fungi, and protozoa. Symptoms can range in severity from fevers of
unknown etiology to life-threatening hemorrhage and perforation. This review
summarizes recent case reports, clinical studies, and reviews pertaining to
pathogens that uniquely cause disease, more frequently cause disease, or cause
more severe disease in the immunocompromised host than in the immunocompetent
host.
PMID- 17031228
TI - Role of probiotics in the treatment of intestinal infections and inflammation.
AB - Despite the relative success of analogous approaches in soil, aquatic, and animal
environments, the enhancement of human health through probiotic consumption has
not been generally endorsed in modern medicine. Laboratory-based studies are
elucidating the mechanisms that mediate the properties attributed to beneficial
lactic acid bacteria and Saccharomyces species in vivo. This research is now
providing fundamental evidence to support observations of adhesion of probiotic
species to intestinal tissue, antimicrobial activities, and immunomodulation.
Probiotics appear to have a promising future in the treatment of certain
disorders. Rigorously performed, controlled, double-blinded trials will overcome
doubts relating to efficacy in vivo and open avenues along which probiotic-based
therapies will rapidly progress. As a result of our emerging understanding of
microbial activities and gene expression in situ, novel strategies will combine
complementary probiotic functionalities in the form of microbial consortia or
genetically enhanced organisms. As scientific knowledge and biotechnologic
proficiency advance at an accelerating pace, the requirement for informed
legislation and for mechanisms of effectively delivering these therapies to the
sites of their intended function may limit the applications of probiotics.
PMID- 17031229
TI - Risk factors for waterborne enteric infections.
AB - Risk factors for waterborne enteric infections are deduced primarily from
outbreak surveillance data; however, in the United States, only a fraction of the
estimated water-related outbreaks are reported through passive surveillance. In
the past several years, advances in molecular detection techniques have furthered
our knowledge about foodborne and waterborne causes of gastroenteritis, allowing
the association of certain pathogens with biologic and exposure-related
susceptibilities in their hosts. This article summarizes some of the recent data
characterizing susceptibility to three common waterborne
pathogens:Cryptosporidium, a protozoan; Norwalk-like virus; and the bacterium
Escherichia coli O157:H7. The infectious dose of Cryptosporidium varies by
several orders of magnitude by strain, and repeated low-level exposure in
drinking water may be protective. Some people may be innately immune to Norwalk
like virus, despite multiple exposures. A major risk factor for E. coli O157:H7
infection is exposure to shallow groundwater sources contaminated with animal
waste.
PMID- 17031231
TI - Expression of lymphoid enhancer factor/T-cell factor proteins in colon cancer.
AB - Molecular genetic analysis of colon cancers has established that the Wnt
signaling pathway is involved in early tumor development. Mutation of midstream
components can activate the pathway, making it independent of Wnt ligands and
maintaining constant pressure to change target gene expression. The transcription
factors that connect the pathway to target genes are members of the lymphoid
enhancer factor/T-cell factor (LEF/TCF) family. The genes for two members of this
family, TCF 7 and LEF 1, produce full-length forms that mediate Wnt signals and
truncated dominant negative forms that limit Wnt signals and may function as
growth suppressors. Results from studies of their expression in colon cancer
suggests that because Wnt-linked cancers progress to malignancy, there may be a
strengthening of the Wnt signal by selective expression of the activating forms
of LEF/TCFs and a bias against suppressing, truncated forms.
PMID- 17031232
TI - Hamartomatous polyposis syndromes: genetic pathways.
AB - Hamartomatous polyposis syndromes are a group of clinically distinct but perhaps
genetically related disorders in which the predominant finding is multiple
hamartomatous polyps in the gastrointestinal tract. These syndromes are
transmitted in an autosomal dominant fashion to offspring, but sporadic forms do
exist in which the biological parents lack an identified germline mutation.
Despite the nondysplastic histologic characteristics of their polyps, each
hamartomatous syndrome carries an elevated risk for cancer at specific organ
sites. Several genes have been identified as mutated in the germline from these
syndromes, and they provide clues to the pathogenesis of the polyps and may
explain some of the elevated cancer risk. Pathways involved in the hamartomatous
syndromes include those of vascular endothelial growth factor, the transforming
growth factor beta superfamily, and antagonizing the effects of Akt/protein
kinase B.
PMID- 17031233
TI - Epigenetics in colorectal cancer.
AB - Malignant transformation is now known to require a series of molecular
alterations that disrupt a limited number of pathways including autocrine and
paracrine responses to growth factors, cell-cycle control, senescence, motility,
and invasion. Studies on hereditary cancers have established genetic changes as
the primary driving force for these molecular alterations. Recently, however, it
has been recognized that epigenetic changes, defined as clonal changes in gene
expression without accompanying changes in primary DNA coding sequence, can also
be a driving force in neoplastic transformation, for selected genes, and in
specific tumors. DNA methylation within gene promoters and associated alterations
in histone acetylation appear primary mediators of epigenetic inheritance in
cancer cells. In the large intestine, aberrant DNA methylation arises very early,
initially in normal-appearing mucosa, and may be part of the age-related field
defect observed in sporadic colorectal neoplasia. Aberrant methylation also
contributes to later stages of colon cancer formation and progression through a
hypermethylator phenotype termed cytosine phosphoguanosine (CpG) island
methylator phenotype (CIMP), which appears to be a defining event in
approximately half of all sporadic tumors. In sporadic colon cancer, CIMP has
distinct epidemiologic and clinical features and is responsible for most cases of
microsatellite instability related to hMLH1 inactivation. The recognition of
epigenetic changes as a driving force in colorectal neoplasia opens new areas of
research in disease epidemiology, risk assessment, screening, and treatment.
PMID- 17031234
TI - The pathogenesis of Hirschsprung disease.
AB - Hirschsprung disease is the most common congenital malformation of the enteric
nervous system. Phenotypic expression is variable because of incomplete
penetrance, and the pathogenesis is multifactorial. Although mutations of the RET
tyrosine kinase gene remain the most commonly identified cause, there are now
eight separate human gene loci identified whose mutations result in this disease.
Analysis of these gene products in experimental animal models and cell systems
has led to an increasing elucidation of the signaling pathways that are in
operation during specific embryonic time stages and that direct the spatial
arrangements and differentiation of enteric neuroblasts. Mutation analysis
through in vitro cell expression studies has led to detailed descriptions of the
affected microdomains of signal pathway receptors and the cellular pathogenesis
of abnormal signaling that leads to apoptosis of developing neurons before the
completion of enteric nervous system development. The full description of the
pathogenesis of this disorder awaits the definition of new genetic loci, multiple
gene interactions, and the acknowledgment of random events that may lead to
aganglionosis of the distal bowel.
PMID- 17031235
TI - Implementation of colorectal cancer screening: the challenge.
AB - Colorectal cancer is the second leading cause of cancer death among men and women
in the United States, and its incidence is increasing in other developed
countries throughout the world. Efficacious and cost-effectiveness screening
measures exist for colorectal cancer, but successful implementation at a
community level remains challenging. This article is a summary of recently
published information on cost-effectiveness of colorectal screening, attempts to
enhance acceptance and compliance by physicians and the public, and legislative
efforts to ensure access to screening.
PMID- 17031236
TI - Endoscopic treatment of lower gastrointestinal bleeding.
AB - Urgent colonoscopy has emerged as the initial diagnostic and main therapeutic
tool in the evaluation and treatment of colonic lower gastrointestinal bleeding.
Endoscopic therapy can effectively treat most cases of colonic bleeding with a
demonstrable improvement in clinical outcome parameters. The identification of
high-risk stigmata of hemorrhage enables selective targeting of endoscopic
therapy to lesions at high risk of rebleeding. Advances in technologies such as
novel mechanical methods of hemostasis (eg, metallic clips), injection techniques
(eg, cyanoacrylate injection), and the widening application of established
endoscopic hemostatic techniques (eg, rubber-band ligation) to colonic lesions
offers the possibility of further improvements in the efficacy of endoscopic
hemostasis. Clinical trials are needed to compare these novel endoscopic
techniques with more conventional approaches to establish the best form of
endoscopic therapy for different bleeding lesions and finally to establish more
definitively the optimal timing of colonoscopy.
PMID- 17031237
TI - Update on immunologic basis of celiac disease.
AB - During the past few years several seminal studies have greatly expanded our
knowledge on celiac disease pathogenesis. This review focuses on aspects that
have been most properly addressed and where substantial new information has been
gathered include. Topics covered include (a) the identification of T-cell
epitopes in gluten and the mechanisms of specific T-cell response in celiac
disease small intestine; (b) the mechanisms of induction of mucosal lesion; and
(c) the putative role of non-T-cell factors in driving mucosal response to
gliadin. After discussing a brief history of the "quest for the cause of celiac
disease," we examine the development of the typical celiac lesion (the crypt
hyperplastic mucosal atrophy) as it generally unfolds: the increased entry of
dietary antigens; the early changes, linked to specific components of the innate
immunity rather than to its adaptive branch; the most thoroughly investigated
subsequent response, involving a strong T-cell response and cytokines; and the
factors responsible for enterocytes' death. The emerging pattern is that of a
complex interaction of factors, although far from being completely understood,
but fascinating as it opens an incredible window of knowledge on an autoimmune
disorder whose environmental factor is known, whose autoantigen is known, whose
autoantibodies are known: a truly unique situation in medicine.
PMID- 17031238
TI - Bibliography current world literature.
PMID- 17031239
TI - Colorectal cancer screening, comorbidity, and follow-up in elderly patients.
AB - OBJECTIVE: We examined the relationship between comorbid disease and performance
of complete colon examination by colonoscopy or double contrast barium enema
(DCBE) after positive screening fecal occult blood test (FOBT) in patients 70
years of age or older. BACKGROUND: FOBT is an accepted form of colorectal cancer
(CRC) screening. Factors that influence follow-up of positive FOBT have been
largely unknown. METHODS: Patients aged 70 years and older with positive FOBT
between March 1, 2000 and Feb 28, 2001 were included in this retrospective
medical record review performed at a single center. Comorbidity was measured by
the Charlson Comorbidity Scale. RESULTS: : In our sample of 266 subjects, 193
(73%) were referred for evaluation of positive FOBT and 109 (41%) underwent a
colonoscopy or DCBE within 12 months. Using the Charlson score for comorbidity,
27% of our sample scored 0, 24% scored 1, and 23% scored 2 while 26% had a
Charlson score of 3 or higher. There was no association between Charlson score
(0, 1, 2, and > or =3) and referral for evaluation (chi test, P = 0.28) or
performance of a complete colon examination (chi test, P = 0.38). CONCLUSIONS: In
this sample, only 41% of patients with positive FOBT underwent a full colon
examination within 12 months of a positive FOBT. Although comorbidity burden was
considerable, there was no association between comorbidity score and referral for
or performance of a full colon examination. These results suggest that
inappropriate patients receive CRC screening, which may contribute to delays for
screening appropriate patients and diagnostic delays for others with positive
screening test findings.
PMID- 17031240
TI - Cardiac autonomic dysregulation in patients with acute hepatitis.
AB - BACKGROUND: Autonomic dysfunction is common in patients with chronic liver
disease, but it is still unclear whether acute hepatitis coincides with
alterations in autonomic functions. METHODS: We evaluated the heart rate
variability (HRV) of 10 patients with acute hepatitis (6 males, 4 females; mean
age, 44.0 y; range, 20-69 y). Frequency-domain analysis of short-term and
stationary R-R intervals was performed on the first day of admission to detect
low-frequency power (LF; 0.04-0.15 Hz), high-frequency power (HF, 0.15-0.40 Hz),
the ratio of LF to HF (LF/HF), and LF in normalized units (LF%). The same
measurement was repeated on the 7th day of admission. RESULTS: We found that
there was a significant increase of HF as well as variance of the R-R interval on
the 7th day after admission (P < 0.05). There was a significant negative
correlation between HF and the change of total bilirubin (P < 0.05). CONCLUSIONS:
The study demonstrates a change in cardiac vagal tone associated with acute
hepatitis by analysis of HRV, and such alteration is less pronounced later during
the clinical course of acute hepatitis.
PMID- 17031241
TI - Chlamydophila (Chlamydia) pneumoniae infection of human astrocytes and microglia
in culture displays an active, rather than a persistent, phenotype.
AB - BACKGROUND: The intracellular pathogen Chlamydia pneumoniae can cause persistent
infections during which its morphologic, molecular, and pathogenic
characteristics differ importantly from those of active infection. This bacterium
was identified within astrocytes and microglia in the brain of late-onset
Alzheimer disease patients. We investigated whether infection of these two host
cell types displays an active or persistent growth phenotype. METHODS: The human
astrocytoma and microglioma cell lines U-87 MG and CHME-5 (respectively) and the
human epithelial cell line HEp-2 were infected by the standard method with C
pneumoniae strain AR-39. Cultures were harvested at 24, 48, and 72 hours
postinfection and subjected to analysis of inclusion morphology. DNA and RNA were
prepared from portions of each infected culture sample and analyzed for relative
chromosome accumulation and presence or absence of several specific bacterial
mRNAs. RESULTS: Astrocytes and microglial cells infected in vitro with C
pneumoniae displayed inclusions that were indistinguishable from those
characteristic of active infection of the standard HEp-2 host cell line. Real
time polymerase chain reaction (PCR) showed that the relative accumulation of
chlamydial chromosome over time during infection of these two cell lines also was
virtually identical to that in actively infected HEp-2 cells. Reverse
transcriptase PCR (RT-PCR) analyses showed that mRNA from ftsK, pyk, and other
chlamydial genes whose expression is abrogated during persistent infection were
easily identifiable in infected CHME-5 and U-87 MG cells. CONCLUSIONS: In
cultured human astrocytes and microglia, C pneumoniae displays an active, not a
persistent, growth phenotype. This indicates normal passage through the
developmental cycle with its probable concomitant destruction by lysis of some
portion of host cells at the termination of that cycle.
PMID- 17031242
TI - The clinical impact of bacteremia in complicated acute pyelonephritis.
AB - BACKGROUND: Bacteremia has been considered as a surrogate marker of severe
infection in several infectious diseases. However, it remains uncertain whether
the presence of bacteremia correlates with severe infection in patients with
complicated acute pyelonephritis (APN). METHODS: We performed a retrospective
study to investigate the relationship between the presence of bacteremia and
disease severity in complicated APN. To do this, we reviewed medical records from
128 patients diagnosed with complicated APN admitted to Kaohsiung Veterans
General Hospital, Taiwan between January, 2003 and December, 2003. In our
analysis, we compared clinical presentation, treatment response, and outcome in
patients with and without bacteremia. RESULTS: Fifty-four of 128 patients (42%)
were bacteremic. This group of patients presented more frequently with severe
sepsis or septic shock (P < 0.001), compared with nonbacteremic patients. Other
factors that correlated with the presence of bacteremia were older age, diabetes
mellitus, more band forms in neutrophil cell counts, impaired renal function, and
a lower level of serum albumin. Using a multivariate logistic regression
analysis, we show that lower levels of serum albumin (odds ratio, 0.18; 95% CI,
0.05-0.65; P = 0.008) and presence of severe sepsis (odds ratio, 4.76; 95% CI,
1.43-15.84; P = 0.011) were independent factors associated with bacteremia.
Following treatment, the bacteremic group took a longer time to become
defervescent than the nonbacteremic group (5.1 +/- 2.3 vs. 4.2 +/- 1.6 days, P =
0.023). Also, the bacteremic group had a greater mean duration of intravenous
antibiotics administration and longer hospital stays (P < 0.001). Multiple
logistic regression analysis shows that non-Escherichia coli bacteremia, presence
of urolithiasis or hydronephrosis, shorter duration of antibiotics
administration, and being male were significantly associated with recurrence of
urinary tract infection within 6 months. CONCLUSION: Bacteremia in cases of
complicated APN indicates a severe disease, which is more likely to recur in
patients with non-E coli bacteremia. Our study showed that bacteremia is indeed a
useful clinical indicator of severe disease and, if found, should influence
patient management. Therefore, we recommend that blood culture samples should be
taken in all patients with complicated APN.
PMID- 17031243
TI - Effects of histologic type on levels of macrophage colony-stimulating factor in
liquid contents of benign ovarian tumors.
AB - BACKGROUND: Normal ovarian tissue is rich in cytokines. Cytokines are important
in the physiology of ovarian function. Most of the same cytokines that are found
in normal ovarian tissue are also found in association with benign and malignant
tumors in contrast to their functions in normal tissues. Thus, we measured
macrophage colony-stimulating factor (M-CSF) levels in the liquid contents of
benign ovarian tumors--serous cystadenoma, mucinous cystadenoma, and mature
cystic teratoma--and investigated whether M-CSF levels were associated with the
histologic type of the ovarian tumors. METHODS: We enrolled 65 patients, 52 with
benign ovarian tumor and 13 in the early postmenopausal period with symptoms of a
menopausal disorder. Among the 52 patients with benign ovarian tumor, 16 had
serous cystadenoma, 21 had mucinous cystadenoma, and 15 had mature cystic
teratoma. Immediately after surgery, the liquid content was drawn from the
ovarian tumor, then centrifuged, and the separated supernatant was stored at -30
degrees C. The M-CSF level was determined by the sandwich enzyme-linked
immunosorbent assay method with use of three antibodies. RESULTS: The level of M
CSF was 12,513 U/mL (median) (range, 0-169,000 U/mL) in serous cystadenoma, 915
U/mL (0-82,500 U/mL) in mucinous cystadenoma, and 149 U/mL (0-6,230 U/mL) in
mature cystic teratoma. The M-CSF levels increased significantly from mature
cystic teratoma to mucinous cystadenoma to serous cystadenoma. The serum M-CSF
levels were 308 to 499 U/mL in patients with benign ovarian tumor. The M-CSF
levels did not differ significantly among the three groups. The serum M-CSF
levels were 162 U/mL (0-473 U/mL) in menopausal patients. CONCLUSIONS: Elevation
of levels of M-CSF varies according to histologic type in benign ovarian tumors.
This implies that the antitumor activities of M-CSF for serous cystadenoma,
mucinous cystadenoma, and mature cystic teratoma differ by histologic type.
PMID- 17031244
TI - Biomarkers in cardiovascular disease: integrating pathophysiology into clinical
practice.
AB - Biomarkers play an important role in the diagnosis, prognostic assessment, and
management of patients with suspected acute coronary syndromes (ACS). Specific
biomarkers identify different components of the pathophysiology of ACS: troponins
are prototype markers of myocyte necrosis, natriuretic peptides reflect
neurohormonal activation and hemodynamic stress, soluble CD40 ligand is an
indicator of platelet activation, and C-reactive protein, myeloperoxidase, and
monocyte chemoattractant protein-1 reflect various inflammatory processes. When
combined, multiple biomarkers reflecting different pathophysiologic processes
appear to enhance risk stratification, as compared with using individual markers
alone. Advances in proteomic technology promise to identify additional novel
biomarkers that facilitate diagnosis, risk stratification, and selection of
therapies in ACS. In the future, it is hoped that multiple biomarker panels will
form the basis of an individualized approach to the treatment of ACS, in which
therapy is tailored to individual biomarker profiles.
PMID- 17031245
TI - Pericardial involvement as an atypical manifestation of giant cell arteritis:
report of a clinical case and literature review.
AB - PURPOSE: Pericardial effusion has been known to be a rare manifestation of giant
cell arteritis. During the last six decades, only 24 cases have been cited in the
literature. In this report, we describe the case of a patient presenting with
nonspecific symptoms and development of pericardial effusion. PROCEDURES AND
FINDINGS: A 71-year-old woman was admitted to the hospital with low-grade fever,
exertion breathlessness, atypical diffuse muscular pain, and weight loss over a
period of about 5 weeks. Pericardial effusion and giant cell arteritis were
diagnosed by echocardiography and left temporal artery biopsy, respectively.
Treatment with corticosteroids resulted in remarkable improvement of symptoms and
complete remission of pericardial effusion. One year after admission, the patient
remained in a stable good condition, under low steroid maintenance dosage.
CONCLUSIONS: The diversity of clinical manifestations (such as pericardial
effusion) in such a potentially severe disease should alert the physician to
prompt diagnosis and treatment in view of impending irreparable vascular damages,
even in cases in which the initial presentation is quite uncommon.
PMID- 17031246
TI - Pregnancy-induced pancytopenia with cellular bone marrow: distinctive hematologic
features.
AB - Three patients with pregnancy-induced pancytopenia also exhibited variable
features of sideroblastic anemia and amegakaryocytic thrombocytopenia. Treatment
with anti-thymocyte globulin proved highly effective in two cases and a
spontaneous remission occurred in the third. This illness is distinct from the
more commonly reported incidental association of pregnancy with classic aplastic
anemia. Its differentiation from myelodysplasia is also emphasized.
PMID- 17031247
TI - Myocardial involvement in rocky mountain spotted fever: a case report and review.
AB - Rocky Mountain Spotted Fever (RMSF), caused by Rickettia rickettsii, is a serious
tickborne illness that is endemic in the southeastern United States. Although it
is most commonly known as a cause of fever and rash, it can have systemic
manifestations. The myocardium may rarely be involved, with symptoms that can
mimic those of acute coronary syndromes. This report describes a case of
serologically proven RMSF causing symptomatic myocarditis, manifested by chest
pain, elevated cardiac enzyme levels, and decrease myocardial function. After
treatment with antibiotics, the myocarditis resolved. Thus, although unusual, the
clinician should be aware of myocardial disease in patients with appropriate
exposure histories or other clinical signs of RMSF. Close monitoring and an
aggressive approach are essential to reduce mortality rates.
PMID- 17031248
TI - The impact of lifestyle behavior on hypertension awareness, treatment, and
control in a southeastern population.
AB - BACKGROUND: We were interested in determining the rates of hypertension
awareness, treatment, and control in individuals living in the southeastern
United States and evaluating the impact of lifestyle behaviors on these rates.
METHODS: This is a cross-sectional survey of a sample of community dwellers in
the greater Columbia, South Carolina area. The survey was developed from
validated community-based survey questionnaires to evaluate demographic and
social history (age, gender, race-ethnicity, income, and education), hypertension
history (diagnosis and treatment), and lifestyle behavior (servings of fruits and
vegetables [FV] and physical activity [PA] duration and frequency), as well as
blood pressure measurement. RESULTS: A total of 763 people (mean +/- standard
error age 52.4 +/- 0.7 years; 68% women, 53% African American) agreed to be
screened. Of all participants with hypertension (438 [58%]), 82% were aware of
their illness and 79% were on treatment. Of all hypertensive participants, 39%
had their hypertension controlled below 140/90 mm Hg at the time of the survey.
Only 11% reported consuming five or more FV per day and 18% reported PA five or
more times per week. African-Americans consumed less FV (P < 0.001) and performed
less PA (P < 0.001). Those consuming more FV and exercising more frequently had
lower hypertension prevalence and tended to have better control rates.
CONCLUSIONS: In a sample of southeastern residents, the control rate was
suboptimal despite a relatively high rate of treatment. Low levels of FV
consumption and PA were noted especially in African-American patients and may
explain this rate.
PMID- 17031249
TI - Vibrio vulnificus bacteremia associated with chronic lymphocytic leukemia,
hypogammaglobulinemia, and hepatic cirrhosis: relation to host and exposure
factors in 252 V. vulnificus infections reported in Louisiana.
AB - BACKGROUND: Vibrio vulnificus infection in persons with B-chronic lymphocytic
leukemia (B-CLL) or hypogammaglobulinemia has been reported infrequently. PATIENT
AND METHODS: A woman with B-CLL, hypogammaglobulinemia, and hepatic cirrhosis
died of V. vulnificus bacteremia after eating cooked shrimp and crabs. We
reviewed host and exposure data in 252 cases of V. vulnificus infection reported
in Louisiana during the interval of 1980 through 2004. RESULTS: V. vulnificus was
isolated from blood in 122 cases (48.8%). Preexisting conditions in 138 cases
included liver disease (41.3%), malignancy (13.8%), and immunosuppression (9.4%).
The prevalence of preexisting conditions was significantly greater in cases with
positive blood cultures than in cases with positive wound or stool cultures.
Exposure data in 116 cases revealed crab consumption without raw oyster
consumption or seawater exposure in 3.4%. CONCLUSION: The present patient had
several conditions associated with increased risk of V. vulnificus infection and
bacteremia, especially hepatic cirrhosis, but her route of exposure to V.
vulnificus was unusual.
PMID- 17031250
TI - ACSM Fellow Ken Baldwin and colleagues discover a new antisense retrograde
mechanism of gene regulation.
PMID- 17031251
TI - Muscle reflexes in motion: how, what, and why?
AB - Methods have been developed to study excitatory and inhibitory reflexes during
human movements because dramatic task-dependent changes occur between different
voluntary activities, and phase-dependent changes occur within cyclic movements.
Interestingly, segmental reflexes are relatively unimportant for standing
balance, although reflex responses are strong, yet they contribute substantially
to force in several muscles during walking, when some reflex responses are
weaker.
PMID- 17031252
TI - Neural aspects of muscle stretching.
AB - Neural mechanisms contribute significantly to the gains that occur in the range
of motion about a joint with stretching exercises. In the acute condition,
lengthening of a muscle-tendon unit decreases spinal reflex excitability, which
reduces passive tension and increases joint range of motion. Similarly,
participation in a stretch-training program decreases tonic reflex activity and
increases flexibility.
PMID- 17031253
TI - The molecular physiology of human limb immobilization and rehabilitation.
AB - This short review will identify some of the molecular signaling events that
regulate atrophy during immobilization in human skeletal muscle and how
prescribed exercise rehabilitation may influence these signaling events. The
potential for nutritional intervention to positively modulate molecular signaling
and thereby offset muscle wasting and/or accelerate rehabilitation in humans will
also be considered.
PMID- 17031254
TI - Muscle perfusion and metabolic heterogeneity: insights from noninvasive imaging
techniques.
AB - Recent developments in noninvasive imaging techniques have enabled the study of
local changes in perfusion and metabolism in skeletal muscle as well as patterns
of heterogeneity in these variables in humans. In this review, the principles of
these techniques along with some recent findings on functional heterogeneity in
human skeletal muscle will be presented.
PMID- 17031255
TI - PGC-1alpha gene and physical activity in type 2 diabetes mellitus.
AB - Exercise stimulates PGC-1alpha gene expression and increases V O2max, the latter
of which relates inversely with type 2 diabetes risk. Consistently, low levels of
PGC-1alpha mRNA and nucleotide sequence variation at PGC-1alpha associate with
lower level of V O2max and increased diabetes risk. Thus, PGC-1alpha sequence
variation may interact with physical activity to modify diabetes risk via changes
in oxidative energy metabolism.
PMID- 17031256
TI - Toll-like receptor 4: link to the anti-inflammatory effects of exercise?
AB - Evidence is emerging that exercise training has anti-inflammatory effects. Our
early finding that blood cultures from trained subject had a reduced
responsiveness to lipopolysaccharide led to a series of studies in which we
measured toll-like receptor 4--the primary signaling receptor for
lipopolysaccharide. The toll-like receptor 4 expression was consistently lower in
physically active subjects compared with inactive subjects and reduced after
training in previously inactive subjects.
PMID- 17031257
TI - Randomized controlled trials of physical activity and breast cancer prevention.
AB - Observational studies demonstrate that women who exercise have a lower risk of
developing breast cancer compared with sedentary women, but clinical trials are
necessary to demonstrate a decreased effect of exercise on breast cancer. This
review presents a rationale for randomized controlled exercise trials for breast
cancer prevention and proposes a construct for designing such trials.
PMID- 17031258
TI - Exercise-disordered breathing in chronic heart failure.
AB - Patients with heart failure develop various ventilatory abnormalities, including
reduced ventilatory reserves, increased ventilatory demands, and high work and
cost of breathing. They tend to breathe with a rapid-shallow pattern, have low
end-expiratory lung volumes, and may develop rhythmic oscillations in ventilation
and tidal volume. These abnormalities likely contribute to exercise limitations
and are associated with a worsening prognosis.
PMID- 17031259
TI - Increased alveolar and plasma gelatinases activity during postpump syndrome:
Inhibition by inhaled nitric oxide.
AB - Postpump syndrome is associated with systemic inflammation. Matrix
metalloproteinases (MMP)-2 and -9 contribute to proinflammatory and platelet
activator reactions. Nitric oxide (NO) is involved in the regulation of MMPs. The
objectives of our study were to investigate the intensity of inflammation induced
by 3 different surgical procedures, the effects of inflammation on the activity
of MMPs, and the regulation of inflammation by inhaled NO (20 ppm). Inhaled NO
was initiated immediately after tracheal intubation and maintained for the total
duration of the experiments. Thirty pigs were equally randomized into 6 groups
[sham; sham + NO; cardiopulmonary bypass; bypass + NO; bypass +
lipopolysaccharide (1 microg/kg for 50 min); bypass + lipopolysaccharide + NO]
and animals were subjected to anesthesia and mechanical ventilation up to 24 h.
The levels of MMP-2 and MMP-9 in plasma and bronchoalveolar lavage were measured
using zymography. Bypass resulted in a time-dependent rise in MMP activity, an
effect potentiated by lipopolysaccharide. Inhaled NO attenuated the effects of
bypass + lipopolysaccharide. These results confirm that MMP-2 and MMP-9 are
associated with the inflammatory process causing the postpump syndrome.
Preemptive and continuous administration of inhaled NO helps to prevent increased
MMP-2 and MMP-9 activity.
PMID- 17031260
TI - Prevention of postischemic myocardial reperfusion injury by the combined
treatment of NCX-4016 and Tempol.
AB - Nitric oxide (NO) plays a protective role in myocardial ischemia-reperfusion
(I/R) injury. However, the concomitant production of superoxide and other
reactive oxygen species (ROS) during I/R may diminish the bioavailability of NO
and hence compromise the beneficial effects. The objective of this study was to
investigate the protective effect of the coadministration of NCX-4016 [2
(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester] (an NO donor) with
antioxidants Tempol, superoxide dismutase (SOD), or urate on I/R injury. Isolated
rat hearts, perfused with Krebs-Henseleit buffer, were subjected to 30 minutes of
global ischemia, followed by 45 minutes of reperfusion. Before the induction of
ischemia, the hearts were infused for 1 minute with NCX-4016 (100 microM) either
alone or in combination with Tempol (100 microM), SOD (200 U/mL), or urate (100
microM). Hearts pretreated with NCX-4016 showed a significantly enhanced recovery
of function and decreased infarct size and LDH/CK release compared with the
controls. However, treatment of hearts with NCX-4016 + Tempol, SOD, or urate
showed a significantly enhanced recovery of heart function compared with NCX-4016
alone. The treatment of hearts with NCX-4016 + Tempol showed significantly
enhanced NO generation and decreased ROS and dityrosine (a marker of
peroxynitrite) formation. In conclusion, NCX-4016 in combination with Tempol
demonstrated significant cardioprotection and, thus, may offer a novel
therapeutic strategy to prevent I/R-mediated myocardial injury.
PMID- 17031261
TI - Oxidative stress-associated vascular aging is xanthine oxidase-dependent but not
NAD(P)H oxidase-dependent.
AB - Vascular aging is characterized by endothelial dysfunction that is primarily
attributed to increased superoxide production, the exact source of which remains
ambiguous. This study compared the NAD(P)H and xanthine oxidase (XO) systems as
sources of superoxide and impaired vascular function in aging. Male Sprague
Dawley rats, 4-months-old (young) and 18-months-old (Aging), were used. Systolic
blood pressure was higher (36 +/- 3%) in the aging group compared with young
rats, and this was accompanied by reduced acetylcholine-induced renal
vasodilatation. Urinary excretion of nitrite was lower in the aging rats (P <
0.05), and this was associated with reduced nitric oxide synthase (NOS) activity
and reduced eNOS and iNOS protein expression in the aorta. Aged rats showed a n
approximately twofold increase in free radical generation, as evident by
increased plasma 8-isoprostane level, and an approximately fourfold increase in
proteinuria compared with the young rats. Vascular NADP(H) oxidase was unchanged
between both groups, as was the expression of p67phox or p47phox components of
NAD(P)H oxidase. However, XO activity was increased (19 +/- 1%; P < 0.05) as well
as XO expression in the aorta of aging rats. These results suggest that increased
free radical generation-associated increase in SBP in aging rats is XO but not
NAD(P)H oxidase-dependent.
PMID- 17031262
TI - Angiotensin II type 1 receptor blocker attenuates exacerbated left ventricular
remodeling and failure in diabetes-associated myocardial infarction.
AB - Diabetes mellitus adversely affects the outcomes in patients with myocardial
infarction (MI), due in part to the exacerbation of left ventricular (LV)
remodeling. Although angiotensin II type 1 receptor blocker (ARB) has been
demonstrated to be effective in the treatment of heart failure, information about
the potential benefits of ARB on advanced LV failure associated with diabetes is
lacking. To induce diabetes, male mice were injected intraperitoneally with
streptozotocin (200 mg/kg). At 2 weeks, anterior MI was created by ligating the
left coronary artery. These animals received treatment with olmesartan (0.1
mg/kg/day; n = 50) or vehicle (n = 51) for 4 weeks. Diabetes worsened the
survival and exaggerated echocardiographic LV dilatation and dysfunction in MI.
Treatment of diabetic MI mice with olmesartan significantly improved the survival
rate (42% versus 27%, P < 0.05) without affecting blood glucose, arterial blood
pressure, or infarct size. It also attenuated LV dysfunction in diabetic MI.
Likewise, olmesartan attenuated myocyte hypertrophy, interstitial fibrosis, and
the number of apoptotic cells in the noninfarcted LV from diabetic MI. Post-MI LV
remodeling and failure in diabetes were ameliorated by ARB, providing further
evidence that angiotensin II plays a pivotal role in the exacerbated heart
failure after diabetic MI.
PMID- 17031263
TI - Rho kinase contributes to androgen amplification of renal vasoconstrictor
responses in the spontaneously hypertensive rat.
AB - Androgens modulate vascular tone and hypertension development. Rho kinase
contributes to norepinephrine- (NE) and vasopressin- (AVP) induced
vasoconstriction. This study tested the hypothesis that Rho kinase contributes to
androgen amplification of renal vasoconstrictor responses to NE or AVP in
isolated perfused kidney of spontaneously hypertensive rats (SHRs).SHRs (5 weeks)
underwent sham operation, castration, or castration with testosterone
replacement. At 16-17 weeks, mean arterial pressure and heart rate were measured
in conscious SHRs. Renal vascular reactivity to NE (10 to 10 mol) and to AVP (10
to 10 mol) was assessed in an isolated perfused kidney preparation before and
after Rho kinase inhibitor treatment (fasudil; 15 microM). Castration reduced
mean arterial pressure, whereas testosterone treatment of castrated SHRs
increased mean arterial pressure significantly. The dose-response curves to NE
and AVP obtained in isolated perfused kidneys from castrated SHRs were displaced
to the right of those obtained in sham-operated and castrated + testosterone
treated SHRs. Fasudil treatment produced a rightward shift in the dose-response
curves for each agonist in all of the groups and greatly attenuated the
differences in renal vascular reactivity to NE and AVP among the 3 groups of
SHRs.Collectively, these findings indicate that androgen modulation of
hypertension development in the SHR involves a fasudil-sensitive pathway and
suggest that further study is warranted in this area.
PMID- 17031264
TI - Effects of long-term oral dipyridamole treatment on coronary microcirculatory
function in patients with chronic stable angina: A substudy of the persantine in
stable angina (PISA) study.
AB - AIMS: A meta-analysis of 13 randomized placebo-controlled trials demonstrated a
benefit for dipyridamole therapy, particularly with longer duration of treatment.
Although the mechanism of this effect is not well understood, dipyridamole
increases endogenous tissue adenosine, which may have a beneficial effect on
myocardial perfusion. Therefore, we measured the effects of dipyridamole on
myocardial blood flow (MBF) and coronary flow reserve (CFR) by using positron
emission tomography and H2O in patients with coronary artery disease. METHODS:
Forty-four patients with angiographically documented coronary artery disease were
double-blind randomized to either oral dipyridamole [200 milligrams (mg) twice
daily (bd)] or placebo as add-on to conventional antianginal treatment for 24
weeks. MBF was measured at rest and during dobutamine stress at baseline and
study completion for the region subtended by the most severe coronary artery
stenosis (Isc) and remote myocardium subtended by arteries with minimal or no
disease (Rem). CFR was calculated as MBF-peak/MBF-rest. RESULTS: Thirty-five
patients completed the study. Isc MBF-rest decreased in patients receiving
dipyridamole (0.10 mL/minute/g; P = 0.03) and increased in the placebo group
(0.16 mL/minute/g; P = 0.01) during the 24-week study. No significant change in
MBF-peak was demonstrated in either group. Consequently, Isc-CFR increased
significantly in patients receiving dipyridamole (1.65 +/- 0.47 vs 1.83 +/- 0.67;
P < 0.05). By contrast, Isc-CFR decreased significantly in those receiving
placebo (1.74 +/- 0.44 versus 1.38 +/- 0.46; P < 0.03). No change was seen in Rem
CFR territories. CONCLUSIONS: At the end of treatment, a reduction in baseline
MBF but no significant changes in hyperemic MBF were observed in ischemic
myocardial territories, and therefore the significance of the observed
improvement in CFR remains unclear.
PMID- 17031265
TI - Atrial angiotensinase activity in hypothyroid, euthyroid, and hyperthyroid rats.
AB - Thyroid dysfunction produces marked cardiovascular responses. Hypothyroidism and
hyperthyroidism cause important changes in the circulating renin-angiotensin
system (RAS). Modifications in cardiac RAS have also been involved in
cardiovascular alterations. Studies have revealed that thyroid hormones activate
some components of cardiac RAS. Angiotensin (Ang) peptides are regulated by the
activity of several aminopeptidases (AP) called angiotensinases. Previous results
in our laboratory have demonstrated that thyroid dysfunction altered
angiotensinase activities in hypothalamus, pituitary, and kidney. In the present
study, we investigated the relationship between thyroid status and local
angiotensinase activities in the atrium of hypothyroid, euthyroid, and
hyperthyroid adult male rats. We have determined fluorometrically soluble and
membrane-bound alanyl, glutamyl, and aspartyl aminopeptidase activities using
naphthylamide derivatives as substrates. These activities have been,
respectively, involved in the metabolism of Ang III to Ang IV, Ang II to Ang III,
and Ang I to des-Asp Ang I. Hyperthyroidism was induced with subcutaneous
injections of tetraiodothyronine (300 microg/kg/day), and the hypothyroid rats
were obtained with 0.03% methimazole via the drinking water. Compared with that
in euthyroid rats, a highly significant increase (by 50%) of soluble aspartyl
aminopeptidase activity (P < 0.001) was observed in the atrium of hyperthyroid
and hypothyroid animals. In membrane fractions, T4 treatment produced an increase
in alanyl aminopeptidase (37%; P < 0.05) and aspartyl aminopeptidase activities
(30%; P < 0.01). These results suggest higher formation of des-Asp Ang I in both
hypothyroid and hyperthyroid rats but also suggest higher metabolism of Ang III
to Ang IV in hyperthyroid animals, which is in agreement with the described
alterations of cardiac RAS after thyroid dysfunction.
PMID- 17031266
TI - Role of autonomic nervous activity in the antiarrhythmic effects of magnesium
sulfate in a canine model of polymorphic ventricular tachyarrhythmia associated
with prolonged QT interval.
AB - This study was performed to examine the role played by the autonomic nervous
system in the antiarrhythmic effects of magnesium sulfate (Mg) in a canine model
of polymorphic ventricular tachyarrhythmia facilitated by anthopleurin-A and a
slower heart rate induced QT interval prolongation. In 6 experiments, complete
atrioventricular block was created to control the heart rate and bradycardia at
800- to 1500-ms cycle lengths was applied for 60 sec before and after drug
induced autonomic block. Transmural unipolar electrograms were recorded from
multipolar needle electrodes, and activation-recovery intervals (ARI) were
measured. Before drug-induced autonomic block, polymorphic ventricular
tachyarrhythmia developed in all 6 experiments during bradycardia before but not
after the administration of Mg (0.2 ml/kg intravenous bolus). During drug-induced
autonomic block, triggered premature activity decreased without significant
changes in underlying dispersion of repolarization and polymorphic ventricular
tachyarrhythmia developed during bradycardia in 1 experiment. Administration of
Mg during drug-induced autonomic block eliminated premature activity and
polymorphic ventricular tachyarrhythmia during bradycardia. The distribution of
left ventricular (LV) and right ventricular repolarization and dispersion of
transmural repolarization were analyzed before and 60 sec after Mg administration
during ventricular pacing at 80 bpm. Mg caused a modest shortening of ARI at all
sites before and after drug-induced autonomic block. Since ARI shortening was
greater at the mid-myocardial sites than at other LV sites, Mg decreased
transmural ARI dispersion from 77 +/- 16 to 46 +/- 21 ms before drug-induced
autonomic block and from 79 +/- 7 to 51 +/- 16 ms after drug-induced autonomic
block. The antiarrhythmic effects of Mg in this model of long QT syndrome were
attributable to its direct pharmacological properties and not to changes in
ambient autonomic nervous activity. The blockade of sympathetic activity
decreased the incidence of premature events and partially suppressed polymorphic
ventricular tachyarrhythmia in this model.
PMID- 17031267
TI - Direct effect of F12511, a systemic inhibitor of Acyl-CoA cholesterol
acyltransferase on bovine aortic endothelial cells.
AB - F12511(S)-2',3',5'-trimethyl-4'-hydroxy-alpha-dodecylthio-alpha-phenylacetanilide
(F12511) is a new Acyl-CoA cholesterol acyltransferase (ACAT) inhibitor that not
only reduces the plasma cholesterol levels but also has anti-atherosclerotic
actions in animals models. The study's aim was to analyze if F12511 may directly
modify the ability of tumor necrosis factor--alpha (TNF-alpha)-incubated bovine
aortic endothelial cells (BAEC) to express endothelial nitric oxide synthase
(eNOS) protein and inflammatory-related proteins such as platelet endothelial
cell adhesion molecule (PECAM) and CD40 ligand (CD40L). The addition of
increasing concentrations of F12511 (10 to 10 mol/L) failed to modify the level
of eNOS protein expressed in control BAEC. TNF-alpha (10 ng/mL) reduced the
expression of eNOS protein. In TNF-alpha--incubated BAEC, F12511 protected eNOS
expression in a concentration-dependent manner. TNF-alpha stimulated the
expression of both CD40L and PECAM in cultured BAEC. F12511 (10 mol/L) failed to
modify the expression of CD40L and PECAM in control and TNF-alpha-incubated BAEC.
Reverse transcriptase polymerase chain reaction showed a marked expression of the
ACAT-2 isoform and absent of expression of the ACAT-1 isoform in BAEC. The
presence of ACAT-2 isoform in BAEC was further confirmed by Western blot. F12511
failed to modify the expression of the proinflammatory associated proteins PECAM
and CD40L in the endothelium but protected eNOS expression in the endothelial
cells exposed to inflammatory conditions.
PMID- 17031283
TI - Avastin and new treatments for AMD: where are we?
PMID- 17031284
TI - Development of ranibizumab, an anti-vascular endothelial growth factor antigen
binding fragment, as therapy for neovascular age-related macular degeneration.
AB - BACKGROUND: Angiogenesis is a key aspect of the wet form of age-related
neovascular (AMD), the leading cause of blindness in the elderly population.
Substantial evidence indicated that vascular endothelial growth factor (VEGF)-A
is a major mediator of angiogenesis and vascular leakage in wet AMD. VEGF-A is
the prototype member of a gene family that includes also PlGF, VEGF-B, VEGF-C,
VEGF-D and the orf virus-encoded VEGF-E. Several isoforms of VEGF-A can be
generated due to alternative mRNA splicing. Various VEGF inhibitors have been
clinically developed. Among these, ranibizumab is a high affinity recombinant Fab
that neutralizes all isoforms of VEGF-A. The article briefly reviews the biology
of VEGF and then focuses on the path that led to clinical development of
ranibizumab. RESULTS: The safety and efficacy of ranibizumab in the treatment of
neovascular AMD have been evaluated in two large phase III, multicenter,
randomized, double-masked, controlled pivotal trials in different neovascular AMD
patient populations. Combined, the trial results indicate that ranibizumab
results not only in a slowing down of vision loss but also in a significant
proportion of patients experiencing a clinically meaningful vision gain. The
visual acuity benefit over control was observed regardless of CNV lesion type.
Furthermore, the benefit was associated with a low rate of serious adverse
events. CONCLUSIONS: Ranibizumab represents a novel therapy that, for the first
time, appears to have the potential to enable many AMD patients to obtain a
meaningful and sustained gain of vision. On June 30 2006, ranibizumab was
approved by the US Food and Drug Administration for the treatment of wet AMD.
PMID- 17031285
TI - Vitreous levels of unbound bevacizumab and unbound vascular endothelial growth
factor in two patients.
AB - BACKGROUND: Vitreous levels of unbound bevacizumab (Avastin) and unbound vascular
endothelial growth factor (VEGF) were determined in two patients. Patient 1
underwent repair of an 8-day-old rhegmatogenous retinal detachment 4 weeks after
a single intravitreal bevacizumab injection, and Patient 2 underwent vitreous
biopsy for endophthalmitis 48 hours after a combined bevacizumab and
triamcinolone injection. METHODS: The samples of vitreous fluid were analyzed for
unbound bevacizumab and unbound VEGF levels using microsphere immunoassays
targeted for bevacizumab and VEGF. RESULTS: In Patient 1, the unbound bevacizumab
level was 0.16% of the loading dose (or 500,000 pg/mL) and the unbound VEGF
concentration was <41 pg/mL 4 weeks after the bevacizumab injection. In Patient
2, the unbound bevacizumab level was 53% of the loading dose (or 166,000,000
pg/mL) at 48 hours, with an unbound VEGF level of <41 pg/mL. CONCLUSION: A single
dose of intravitreal bevacizumab is likely to provide complete intravitreal VEGF
blockade for a minimum of 4 weeks, with an intravitreal bevacizumab half-life of
approximately 3 days.
PMID- 17031286
TI - Evaluation of anterior chamber inflammatory activity in eyes treated with
intravitreal bevacizumab.
AB - PURPOSE: To evaluate the effect of intravitreal bevacizumab on anterior chamber
inflammatory activity. METHODS: Sixty-one consecutive patients with neovascular
age-related macular degeneration were examined before, 1 day, and 1 week after
intravitreal administration of 1 mg of bevacizumab (0.04 mL) for neovascular age
related macular degeneration. The intravitreal injection was performed under
sterile conditions. Twenty-one fellow eyes served as controls. The anterior
chamber inflammatory activity was evaluated using biomicroscopy and the laser
flare meter (Kowa FM-500, Kowa Company, Ltd., Tokyo, Japan). RESULTS: None of the
61 consecutive patients had a significant, clinically detectable inflammatory
response within 1 week of follow-up. Anterior chamber inflammatory activity
measured by the laser flare meter ranged from 1.9 counts/ms to 70.0 counts/ms
(mean +/- SD, 13.2 +/- 16.9 counts/ms; 95% confidence interval [CI], 7.8-18.6)
before treatment. One day and 1 week after injection, values were between 3.2
counts/ms and 30.0 counts/ms (mean +/- SD, 9.1 +/- 6.2 counts/ms; 95% CI, 7.2
11.1) and 2.0 counts/ms and 25.1 counts/ms (mean +/- SD, 7.3 +/- 4.6 counts/ms;
95% CI, 5.8-8.8), respectively. There was a significant reduction of anterior
chamber flare at 1 week compared with baseline (P = 0.031). The control eyes had
constantly low flare measures. CONCLUSION: No inflammatory response was detected
clinically and by the laser flare meter after intravitreal bevacizumab
administration. The slight reduction in anterior chamber flare could be due to
the known antiinflammatory effect of anti-vascular endothelial growth factor
therapy.
PMID- 17031287
TI - Safety of intravitreal injection of bevacizumab in rabbit eyes.
AB - PURPOSE: To evaluate the safety of intravitreal injection of bevacizumab in
rabbits using electrophysiological testing and histopathologic analysis. METHODS:
New Zealand albino rabbits were injected in one eye with control antibody (n =
2), 0.05 mL of bevacizumab (n = 3), or 0.2 mL of bevacizumab (n = 3).
Electroretinograms were obtained 1 week and 4 weeks after injection. Histologic
analysis was performed after completion of the electroretinographic studies.
RESULTS: No statistical differences were seen in scotopic and photopic a- and b
wave amplitudes between untreated control and bevacizumab-injected eyes. No
histopathologic differences were identified between untreated control and
bevacizumab-injected eyes. CONCLUSION: Our study did not find evidence of retinal
toxicity from a single intravitreal injection of bevacizumab in rabbits.
PMID- 17031288
TI - One-year safety and efficacy of intravitreal triamcinolone acetonide for the
management of macular edema secondary to central retinal vein occlusion.
AB - PURPOSE: To evaluate the safety and efficacy of intravitreal triamcinolone
acetonide (IVTA) as treatment for macular edema associated with central retinal
vein occlusion (CRVO). METHODS: A retrospective review was performed of data for
40 consecutive patients (40 eyes) with CRVO and macular edema treated with IVTA
at the Bascom Palmer Eye Institute (Miami, FL). RESULTS: Median duration of
symptoms before the first injection was 3 months (range, 1 day to 8 years).
Median Snellen visual acuity was 20/400 at baseline (range, 20/60 to light
perception; n = 40), 20/300 at 1 month (P = 0.010; n = 37), 20/300 at 3 months (P
= 0.007; n = 33), 20/400 at 6 months (P = 0.726; n = 28), and 8/200 at 1 year (P
= 0.569; n = 17). Vision improved by > or =3 lines in 21% of eyes at 1 month, 27%
at 3 months, 14% at 6 months, and 12% at 1 year. Visual acuity was unchanged from
baseline in 71% of eyes at 6 months and 1 year. By 1 year, 50% of eyes received
more than one injection (mean = 1.6 injections; range 1-4 injections). Overall,
intraocular pressure increased by > or =10 mmHg in 24% of eyes at 1 year.
Trabeculectomy was performed on 2 of 12 eyes with preexisting open-angle
glaucoma. CONCLUSION: IVTA can substantially improve vision in some patients, but
most patients have stable visual acuity compared with baseline at 1 year despite
repeated injections.
PMID- 17031289
TI - Intravitreal triamcinolone acetonide treatment of macular edema associated with
central retinal vein occlusion.
AB - PURPOSE: To evaluate treatment of macular edema associated with central retinal
vein occlusion (CRVO) using intravitreal triamcinolone acetonide. METHODS:
Retrospective review of data for 29 eyes of 29 patients with CRVO and macular
edema treated with intravitreal triamcinolone acetonide. Initial visual acuity,
intraocular pressure, and history of glaucoma were recorded. Final visual acuity,
intraocular pressure, and adverse events were recorded during the treatment
period. RESULTS: Twenty-nine eyes were treated with intravitreal injection. The
mean follow-up was 348 days. The median initial Early Treatment Diabetic
Retinopathy Study visual acuity was 20/250 (median logMAR, 1.1). The median
visual acuity 3 months after injection was 20/125 (median logMAR, 0.8). This
difference was statistically significant. The median final visual acuity was
20/250 (median logMAR, 1.1). This difference in visual acuity was not
statistically significant. Elevated intraocular pressure, excluding that related
to neovascularization, occurred in 5 of 22 patients. Subgroup analysis revealed
that patients who received multiple injections had better outcomes. CONCLUSION:
Intravitreal triamcinolone acetonide may improve vision transiently but does not
appear to result in a sustained visual acuity benefit for patients with macular
edema associated with CRVO. Repeated injections may be necessary. The risk of
glaucoma is significant, and additional study is required to further characterize
this and other risks.
PMID- 17031290
TI - Outcomes of macular hole surgery and shortened face down positioning.
AB - PURPOSE: Internal limiting membrane (ILM) peeling in macular hole surgery may
allow a shortened period of face down positioning. This study reports the results
of macular hole surgery combined with shortened (3-day) face down positioning.
METHODS: The study was a retrospective review of data for 21 patients (21 eyes)
treated for a macular hole by a single surgeon (G.K.S.). All patients underwent
standard 3-port pars plana vitrectomy with triamcinolone-assisted ILM peeling and
gas tamponade with 16% C3F8 or 25% SF6. Patients were instructed to remain in a
face down position for 3 days at least 8 hours a day and to avoid flat on back
positioning. RESULTS: The main outcome of anatomical closure was achieved in 20
(95%) of 21 eyes. Snellen visual acuity improved >2 lines in 76% (16/21) of
patients. No patient lost >1 line of Snellen visual acuity. Two patients had
postoperative increased (>24 mmHg) intraocular pressure that was successfully
treated with pressure-lowering drops. Initial surgery failed to achieve hole
closure in one patient, but with a second surgery and similar face down
positioning, the hole was closed. CONCLUSIONS: This study found that macular hole
surgery with ILM peeling and a shortened period of face down positioning achieves
excellent anatomical closure and is not associated with significant adverse
outcomes.
PMID- 17031291
TI - Successful treatment of persistent macular holes using "heavy silicone oil" as
intraocular tamponade.
AB - BACKGROUND: Silicone oil tamponade has been suggested in the treatment of
persistent macular hole, but visual outcome is often poor. We describe two
patients who underwent reoperation for persistent macular hole using "heavy
silicone oil" (HSO) tamponade. METHODS: Two patients who underwent vitrectomy,
removal of the posterior vitreous cortex, peeling of the internal limiting
membrane, and long-acting gas tamponade had persistent macular hole 3 months
after surgery. The patients underwent reoperation using an HSO (Oxane Hd, Bausch
& Lomb) as internal tamponade. This tamponade did not require postoperative
posturing and was removed after 3 months. Optical coherence tomography (OCT) was
performed, and visual outcome was determined. RESULTS: OCT images showed that the
HSO bubble conformed well with the retinal surface in the foveal region. Closure
of the macular hole was achieved in both patients. Visual acuity increased from
20/100 to 20/40 in Patient 1 and from 20/600 to 20/100 in Patient 2. CONCLUSION:
HSO can be a useful tool in the treatment of persistent macular hole. OCT images
showed that the tamponade was effective in the upright position in the foveal
region. OCT allowed determination of the time of tamponade removal according to
the anatomical stage of hole closure.
PMID- 17031292
TI - Combined pars plana phacofragmentation, vitrectomy, and Artisan lens implantation
for traumatic subluxated cataracts.
AB - PURPOSE: To report on the outcome of combined pars plana phacofragmentation,
vitrectomy, and Artisan lens implantation in the management of subluxated
cataracts. METHODS: This prospective, interventional, nonrandomized case series
included nine eyes of seven consecutive adult patients with traumatic lens
subluxation. Pre- and postoperative data (complete manifest refraction, best
spectacle-corrected visual acuity, slit-lamp examination findings, intraocular
pressure, fundus status, numerical density of endothelial cells, corneal
thickness, and complications) were collected prospectively for all patients.
RESULTS: After a median postoperative follow-up of 12 months (range, 8-18
months), a mean spherical equivalent of -0.50 +/- 0.87 diopter (range, +1 to
1.50 diopter) was achieved. The mean logarithm of the minimum angle of resolution
visual acuity improved from 1 (preoperatively) to 0.1 (postoperatively) (P =
0.007, Wilcoxon test). Median endothelial cell losses of 15 +/- 8% (P = 0.008)
and 14 +/- 16% (P = 0.011) were registered at follow-ups of 1 month and 12
months, respectively. Postoperative complications included chronic intraocular
inflammation and superior corectopia. CONCLUSIONS: Our procedure appears to be a
safe, accurate, stable, and efficacious option for the management of traumatic
subluxated cataracts in adults. However, longer-term data are needed to evaluate
the corneal endothelium.
PMID- 17031293
TI - Correlation of optical coherence tomography pattern and visual recovery after
vitrectomy with silicone oil for retinal detachment.
AB - PURPOSE: To assess prospectively the features of the macular surface in silicone
oil-filled eyes after surgery by analyzing whether silicone oil affects optical
coherence tomography (OCT) measurements and their reproducibility and whether a
statistical correlation exists between postoperative best-corrected visual acuity
(BCVA) and foveal thickness measured by OCT. METHODS: Twenty eyes of 20 patients
underwent vitrectomy with silicone oil tamponade for retinal detachment. After
vitrectomy, complete ophthalmic examination including determination of BCVA and
OCT was performed to quantify the visual recovery and the foveal thickness.
RESULTS: Ophthalmoscopy revealed that the retina appeared to be reattached in all
20 eyes at 3 months after surgery. BCVA ranged from 0.4 logMAR to 1.7 logMAR, and
foveal thickness ranged from 80 microm to 500 microm. Postoperative foveal
thickness and BCVA had a strong correlation (r = 0.93; P = 0.003). CONCLUSION:
The presence of silicone oil in the vitreous chamber does not change the
reproducibility of OCT measurements of foveal thickness (coefficient of
reproducibility, 1.48%). This study showed high statistical correlation between
BCVA and foveal thickness. Therefore, postoperative BCVA is affected by
postoperative foveal thickness, and visual improvement is limited in eyes with
increased or decreased foveal thickness.
PMID- 17031294
TI - Optical coherence tomography in the diagnosis and monitoring of cystoid macular
edema in patients with retinitis pigmentosa.
AB - PURPOSE: To identify cystoid macular edema (CME) in patients with retinitis
pigmentosa (RP) using optical coherence tomography (OCT) and to evaluate response
to acetazolamide by serial OCT. METHODS: Twenty-nine consecutive RP patients were
included in the study. Patients with CME were treated with acetazolamide (125 or
250 mg/d for 4-12 months). OCT, fluorescein angiography, and determination of
best-corrected visual acuity (BCVA) were performed initially and throughout the
follow-up period. RESULTS: Ten of the 29 patients had CME by OCT. Of these 10
patients, 5 had various degrees of fluorescein leakage by fluorescein
angiography. After acetazolamide treatment, six patients had significant
decreases in macular edema in at least one eye by follow-up OCT. In six patients,
visual acuity improved by > or =1 line in at least one eye. The change of central
foveal thickness shown by OCT was significantly correlated with the change of
logMAR of BCVA (Pearson correlation coefficient [r] = 0.576; P = 0.008). We
observed no differences in the change of central foveal thickness by OCT (Mann
Whitney test; P = 1.000) and in the change of logMAR of BCVA (Mann-Whitney test;
P = 0.106) between patients treated with 125 mg/d acetazolamide and those treated
with 250 mg/d acetazolamide. CONCLUSIONS: These results indicate that OCT is a
valuable tool in the detection and follow-up of CME in RP patients. Treatment
with acetazolamide resulted in marked improvement in OCT-diagnosed CME in RP, but
visual improvement was variable.
PMID- 17031295
TI - Assessment of retinal function in patients with HIV without infectious retinitis
by multifocal electroretinogram and automated perimetry.
AB - PURPOSE: To determine if multifocal electroretinogram (mfERG) testing shows
abnormalities that correspond to perimetric defects in HIV positive patients
without infectious retinitis. METHODS: We studied three groups of patients: HIV
negative controls, HIV high CD4 nadir patients (lowest CD4 T cell count is over
100) and low CD4 nadir patients (below 100 for over 6 months). Twenty-six HIV
positive eyes and 16 HIV negative control eyes were studied by mfERG. A subset of
10 eyes also underwent computerized perimetry for comparison. We analyzed mfERG
by hexagons as well as by quadrants and rings. RESULTS: Of 103 hexagon locations
there was no significant difference in the amplitudes P1 and N1 (nV/degree)
between the three studied groups (p>0.05), similarly, the latencies were not
different (p>0.05). All eyes with significant visual field defects at the 0.01
and 0.005 level (Humphrey pattern deviation; 24-2) were compared to mfERG
amplitudes and latencies at those locations-there were no corresponding defects
in mfERG data (p>0.2). CONCLUSION: In the era of HAART there are still
demonstrable visual field defects and other evidence of damage to the retinal
nerve fiber layer in HIV patients. Our mfERG studies show that the damage appears
to affect the inner retina, the outer retina is spared. Further studies of inner
retinal structure and function are indicated to elucidate this process.
PMID- 17031296
TI - Intravitreal voriconazole for drug-resistant fungal endophthalmitis: case series.
AB - PURPOSE: To report the efficacy of intravitreal voriconazole. METHODS:
Retrospective analysis of an interventional case series of five cases of culture
proven fungal endophthalmitis treated with intravitreal voriconazole was done.
Only cases found to be resistant to conventional antifungal agents were included
in the study. The diagnosis of fungal endophthalmitis was established on the
basis of clinical as well as microbiological examination. All patients received
one or more intravitreal injections of voriconazole. Resolution was determined on
the basis of clinical examination. Resolution of infection and final visual
acuity were the main outcome measures. RESULTS: Resolution of infection was
achieved in all five cases. Visual acuity was better in three cases and was
maintained in two. Of the three patients who had improvement, two had vision
better than or equal to 20/120. Evisceration was avoided in one case with maximal
antifungal treatment including voriconazole. CONCLUSIONS: Voriconazole definitely
adds to the available treatment options for fungal endophthalmitis. Because of
its broad spectrum of activity, it is efficacious in even amphotericin-B- and
fluconazole-resistant fungal endophthalmitis.
PMID- 17031297
TI - X-linked retinoschisis: novel mutation in the initiation codon of the XLRS1 gene
in a large family.
AB - PURPOSE: To describe a novel point mutation in the initiation codon of the XLRS1
gene in a large family and the clinical features of males affected with X-linked
juvenile retino-schisis. METHODS: Genealogic investigation and mutation screening
of the XLRS1 gene were performed for a 4-generation family consisting of 72
members. Affected males were evaluated clinically between 1986 and 2004 with up
to 18 years of follow-up. RESULTS: We identified a novel point mutation (1A>T
transversion) in the initiation codon of the XLRS1 gene in affected males
resulting in an amino acid substitution of methionine to leucine (Met1Leu),
therefore abolishing the translation initiation Met codon. CONCLUSION:
Identification of the disease-causing mutation in this family with long-term
follow-up allows for earlier and more accurate identification of individuals at
risk for this inherited progressive macular degeneration, provides for more
accurate genetic counseling, and contributes to our understanding of the
pathophysiology of this disorder.
PMID- 17031298
TI - A novel complex mutation event in the peripherin/RDS gene in a family with
retinal pattern dystrophy.
AB - PURPOSE: To report a complex mutation in the peripherin/RDS gene found in a
family in whom retinal pattern dystrophy is segregating as an autosomal dominant
trait. METHODS: Clinical data were collected from family members of a large Swiss
family affected by autosomal dominant retinal pattern dystrophy. Single strand
conformation polymorphism (SSCP) analysis of the candidate gene peripherin/RDS
and subsequent sequencing of the first exon were performed. RESULTS: Pattern
dystrophy of the retina was suspected in 18 family members aged 30 years or
older. Assuming a homogeneous phenotype, the candidate locus peripherin/RDS was
investigated. SSCP analysis of the first exon of the peripherin/RDS gene showed
an aberrant pattern in 18 affected individuals. Direct sequencing of polymerase
chain reaction products detected a complex mutation, del265-268GCCA ins AGGGCC,
leading to a stop codon at amino acid position 99. CONCLUSION: To our knowledge,
we report the first complex mutation in the peripherin/RDS gene as the cause of a
mild macular phenotype, supporting the importance of molecular diagnosis in
genetic counseling.
PMID- 17031299
TI - Diagnostic and therapeutic challenges.
PMID- 17031300
TI - Treatment of choroidal neovascularization in pathologic myopia with intravitreal
bevacizumab.
PMID- 17031301
TI - Standing vitrectomy in morbid obesity.
PMID- 17031302
TI - Adhesion of heavy oil to posterior lens capsule.
PMID- 17031303
TI - Biomechanical significance of the human internal limiting lamina.
PMID- 17031304
TI - Application of YAG laser retinopuncture for perfluorocarbon liquid removal from
under retina after vitreoretinal surgery.
PMID- 17031305
TI - Ophthalmomyiasis associated with Fuchs heterochromic iridocyclitis.
PMID- 17031306
TI - Transpupillary thermotherapy for large-sized subfoveal circumscribed choroidal
hemangioma.
PMID- 17031307
TI - Aicardi syndrome: chorioretinal lacunae without corpus callosum agenesis.
PMID- 17031309
TI - Comment on incidence of rhegmatogenous retinal detachment after vitrectomy in
eyes of diabetic patients.
PMID- 17031310
TI - 2006 Otto Aufranc Award Paper: significance of in vivo degradation for
polyethylene in total hip arthroplasty.
AB - Our research group developed an implant retrieval program to study in vivo
degradation of polyethylene. We now have evidence to support our hypothesis that
degradation of radiation-sterilized polyethylene occurs in the body for not only
historical gamma air sterilized liners, but also for conventional gamma inert
sterilized (ArCom) and annealed highly crosslinked polyethylene (Crossfire)
liners as well. Our research has also led to the discovery that the most severe
manifestations of in vivo oxidation typically occur in regions of the liner
experiencing minimal wear, such as the rim of the component, where the body
fluids (containing oxidizing species) have access to the polyethylene. Our data
from historical, ArCom, and Crossfire retrievals all point to a similar scenario
in which the femoral head limits the in vivo oxidation of polyethylene at the
bearing surface. Consequently, provided rim impingement does not occur, and the
polyethylene locking mechanisms remain relatively isolated from oxidizing fluid,
in vivo oxidation does not seem to be clinically important in the first 10 years
of implantation for conventional gamma sterilized polyethylene. We conclude that
in vivo degradation should be included among the list of potential long-term
failure modes for modular polyethylene components for total hip arthroplasty.
PMID- 17031311
TI - An integrated solution to acetabular revision surgery.
AB - The three salient reasons for failure of acetabular revision surgery have been
failure of fixation, wear and lysis, and dislocation. This review focuses on the
major progress made in addressing these three items, leading to an overall
approach integrating three contemporary techniques with a strong likelihood of
improving acetabular revision surgery. These three techniques are the use of
hemispheric cementless acetabular components, alternate bearings, and big heads.
PMID- 17031312
TI - Multimodal analgesia without routine parenteral narcotics for total hip
arthroplasty.
AB - Methods for managing pain after a total hip replacement have changed
substantially in the past 5 years. We documented the outcome of patients treated
with a multimodal pain program designed to avoid parenteral narcotics. Avoidance
of parenteral narcotics can essentially eliminate the complications of
respiratory depression, ileus, and narcotic-induced hypotension. It can minimize
nausea and vomiting which cause dissatisfaction with an operation. Twenty-one of
140 patients (15%) needed parenteral narcotics postoperatively with only nine
patients (6.4%) using parenteral narcotics after the day of surgery. Mean pain
scores were below 3 of 10 on all postoperative days. There were no patients with
respiratory depression or ileus, and four (2.9%) with urinary retention. Nausea
occurred with 35 patients (25%) in the recovery room and in 28 patients (20%)
thereafter. Emesis occurred in five patients (3.6%) with two incidences in the
recovery room. One hundred and thirty-eight patients (98.6%) were discharged home
at a mean of 2.7 seven days postoperatively with 98 (70%) on a single assistive
device. The multimodal pain management program, which avoided parenteral
narcotics, was effective in providing pain relief, nearly eliminating emesis, and
eliminating the severe complications of respiratory depression, urinary tract
infection and ileus, as well as accelerating function.
PMID- 17031313
TI - Femoral supracondylar malunions with varus medial condyle and shortening.
AB - Femoral supracondylar malunions associated with varus deformity of the medial
femoral condyle and shortening are rare, and all techniques for treatment of this
complication reported to date have limitations. A one-stage antegrade locked
intramedullary nailing technique to concomitantly treat these combined disorders
was performed in 19 consecutive patients. The following procedures were
performed: removal of previous implants, supracondylar corrective osteotomy, one
stage lengthening on a fracture table, antegrade static locked intramedullary
nail stabilization, and corticocancellous bone grafting. Seventeen patients with
malunions received regular followup for a median of 2.4 years (range, 1.1-5.2
years). Sixteen malunions healed with a union rate of 94.1% (16 patients) and a
median union period of 4.5 months (range, 3-7 months). Only one nonunion
associated with nail breakage occurred (5.9%; one patient) and one deep infection
recurred (5.9%; one patient). Both patients recovered after appropriate
treatment. All patients had improved knee alignment and function. Antegrade
locked intramedullary nailing is an effective technique for one-stage treatment
of combined disorders in patients with femoral supracondylar malunions.
Complications can be avoided if patients and surgeons are careful during the
treatment course. Protected weightbearing until fracture healing is crucial to
successful treatment.
PMID- 17031314
TI - Two- to 9-year clinical results of alumina ceramic-on-ceramic THA.
AB - From June 1997 to June 2003 we performed 194 total hip arthroplasties on 173
patients using alumina ceramic-on-ceramic bearings as part of a prospective
United States Food and Drug Administration/Investigational Device Exemption
study. The average patient age at surgery was 49.9 years. Minimum followup time
was 2 years (mean 4.3 years, range 2-9 years). We evaluated survival rate,
implant- and nonimplant-related complications. Clinical outcomes included the
Merle d'Aubigne score. We assessed radiographs for signs of osteolysis, component
loosening, and implant wear. No patients had osteolysis and there were no hip
dislocations. Implant survivorship for all hips with aseptic revision of any
component was 96% (CI, 91-100) at 9 year; survivorship for hips without prior
surgery was 99.3%, (CI, 98-100). There was a 1.7% incidence of implant-related
complications. Our data help confirm two United States FDA/IDE studies on alumina
ceramic-on-ceramic total hip arthroplasty that reported low aseptic revision
rates and low revision rates for instability. Total hip arthroplasty using
alumina ceramic-on-ceramic implants is a safe and reliable procedure in the
comparably young and active patient.
PMID- 17031315
TI - Rating of internal fixation and clinical outcome in displaced femoral neck
fractures: a prospective multicenter study.
AB - The influence of precise surgical technique on the clinical outcome of internal
fixation for displaced femoral neck fractures is an under-reported and potential
confounding factor in randomized studies involving internal fixation as a
treatment modality. Two experienced surgeons blindly rated internal fixation
techniques on the perioperative radiographs of 102 patients selected for internal
fixation in a prospective multicenter 2-year followup study. Overall technical,
fracture reduction, and implant positioning ratings were given according to
instruction. One or both raters assigned an inadequate overall rating in 25% of
patients. There was a correlation with 2-year clinical internal fixation failure
for overall technique and fracture reduction rating. Implant positioning did not
correlate with 2-year internal fixation failure. Correlation increased if both
raters agreed on inadequate technique. One inadequate rating indicated a problem
could arise, whereas two inadequate ratings strengthened this problem likelihood.
Adjudication of technique by independent rater(s) is useful, may have clinical
implications, and should be performed routinely in future studies involving
internal fixation in patients with displaced femoral neck fractures.
PMID- 17031316
TI - Viral load and CD4 count dynamics after HIV-1 seroconversion in homosexual and
bisexual men in Rio de Janeiro, Brazil.
AB - PURPOSE: Reliable predictors of HIV disease progression are scarce in developing
countries, where most HIV infections occur. We describe early virologic and
immunologic events among men who have sex with men in Rio de Janeiro, Brazil.
METHODS: Seroconverters from 2 high-risk cohorts were followed for up to 36
months with periodic laboratory evaluations, plasma viral load, and CD4 count
assessments. Viral load and CD4 count mean trajectories were computed. For the
modeled viral loads, mean and median values were 24,480 (4.36 log10) and 19,720
(4.29 log10) copies/mL (range 14,880-58,090), respectively. Median CD4 count was
373 cells/microL (range 260-508). Overall variation on viral loads ranged from
4.3 to 5.2 log10 copies/mL with a visible increase in the viral load starting at
approximately 600 days (n = 12) after estimated time of seroconversion. The
initial period of HIV infection was characterized by an increase in CD4 count (n
= 29) followed by a steep decline starting at approximately 200 days (508 cells,
95% CI: 425 to 569). A gradual decrease was observed in the median CD4 count
thereafter, reaching 281 (95% CI: 100 to 466) at 1000 days after the estimated
date of seroconversion. CONCLUSIONS: Although viral load dynamics resembled those
observed in developed countries, CD4 counts seem to decline at a faster rate than
in the Multicenter AIDS Cohort Study (MACS) cohort. Clinical and survival data
are needed to assess the impact of interventions, such as antiretroviral therapy,
on the clinical course of HIV infection in Brazil.
PMID- 17031317
TI - Acceptability of formula-feeding to prevent HIV postnatal transmission, Abidjan,
Cote d'Ivoire: ANRS 1201/1202 Ditrame Plus Study.
AB - OBJECTIVE: To describe the maternal acceptability of formula-feeding proposed to
reduce postnatal HIV transmission in Abidjan, Cote d'Ivoire. METHODS: Each
consenting HIV-infected pregnant women, age > or =18 years, who received a
perinatal antiretroviral prophylaxis was eligible. Two hierarchical infant
feeding options were proposed antenatally: exclusive formula-feeding or short
term exclusive breast-feeding. Formula-feeding was provided free up to age 9
months. Determinants of acceptability were analyzed using a logistic regression.
Formula-feeding failure was defined as having breast-fed one's child at least
once. RESULTS: Between March 2001 and March 2003, 580 women delivered: 97%
expressed their infant-feeding choice before delivery; 53% chose formula-feeding.
Significant prenatal determinants for refusing formula-feeding were: living with
her partner, being Muslim, having a low educational level, being followed in one
of the study sites, having not disclosed her HIV status, and having been included
within the first 6 months of the project. Among the 295 mothers who formula-fed,
the Kaplan-Meier probability of success of the formula-feeding option was 93.6%
at Day 2 (95% confidence interval [CI]: 90.7% to 96.3%) and 84.2% at 12 months
(95% CI: 79.9% to 88.5%): 46 of 295 (15.6%) women breast-fed at least once, of
whom 41% temporarily practiced mixed-feeding at Day 2 because of social stigma or
newborn poor health. CONCLUSIONS: In settings with general access to clean water,
structured antenatal counseling, and sustained provision of free formula,
slightly over half of HIV-infected women chose to artificially feed their newborn
infant. Low mixed-feeding rates were observed. This social acceptability must be
balanced with mother-child long-term health outcomes to guide safe
recommendations on infant-feeding among HIV-infected women in African urban
settings.
PMID- 17031318
TI - Late diagnosis of HIV infection: trends, prevalence, and characteristics of
persons whose HIV diagnosis occurred within 12 months of developing AIDS.
AB - BACKGROUND: Persons diagnosed late in the course of HIV infection may be
unknowingly transmitting infection and once diagnosed may have worse outcomes and
greater medical expenses. METHODS: Persons diagnosed with AIDS in San Francisco
between 2001 and 2005 were included. Late testers were persons diagnosed with HIV
12 months or less before their AIDS diagnosis. Prevalence trends, demographic and
risk correlates, and predictors of late testing were measured. RESULTS: Among
2139 persons included, 830 (38.8%) were late testers. The prevalence of late
testing was stable between 2001 and 2005. Late testing was more likely among
persons <30 years old (Odds ratio [OR]: 1.99, 95% confidence interval [CI]: 1.4,
2.8), heterosexuals (OR: 1.88, 95% CI: 1.1, 3.1), persons without a reported risk
(OR: 2.88, 95% CI: 1.7, 5.0), persons with private insurance (OR: 1.82, 95% CI:
1.4, 2.4), no insurance (OR: 1.83, 95% CI: 1.4, 2.4), born outside of the United
States (OR: 1.64, 95% CI: 1.2, 2.2), and whose initial AIDS diagnosis was an
opportunistic infection (OR: 2.24, 95% CI: 1.8, 2.8). CONCLUSIONS: A large
proportion of persons with AIDS have tested late in the course of HIV infection
and this proportion has not declined in recent years. Routine testing in medical
settings, and use of rapid oral-fluid testing in traditional and nontraditional
settings may increase early HIV diagnosis.
PMID- 17031319
TI - Home-based antiretroviral care is associated with positive social outcomes in a
prospective cohort in Uganda.
AB - BACKGROUND: Home-based antiretroviral therapy (ART) care in Africa has expanded;
but social outcomes of home-based ART programs are unknown. METHODS: Social
experiences of participants in an antiretroviral therapy program involving weekly
home visits in Uganda were assessed through interviews at enrollment and after 3
months and analyzed using generalized estimating equations. RESULTS: Of 654
participants, 72% were women; median baseline CD4 cell-count was 123 cells/muL.
At follow-up, participants were more likely to report community support (adjusted
odds ratio [OR] 2.10, 95% confidence interval [CI]: 1.46 to 3.03, P < 0.001),
family support (OR 2.65, CI: 2.01 to 3.49, P < 0.001), and relationship
strengthening (OR 2.10, CI: 1.46 to 3.03, P = 0.001) than at baseline; 84%
attributed these experiences to antiretroviral therapy program participation.
There was no change in incidence of negative experiences (P = 0.3). Forty-six
percent of women reported a history of partner abuse, but abuse rates 3 months
before and after program initiation were low (1% vs. 2%, OR 3.20, CI: 0.94 to
10.9, P = 0.063). Of five women who reported abuse associated with program
participation, all had history of domestic violence. Of all participants
reporting outcomes associated with antiretroviral therapy program participation
at follow-up, 464 (79%) had only positive experiences, 35 (6%) had both positive
and negative experiences, and <1% had only negative experiences. CONCLUSIONS:
Participation in a home-based antiretroviral therapy program was associated with
multiple positive social outcomes.
PMID- 17031320
TI - Identification of a novel circulating recombinant form (CRF33_01B) disseminating
widely among various risk populations in Kuala Lumpur, Malaysia.
AB - A molecular epidemiological investigation was conducted among various risk
populations (n = 184) in Kuala Lumpur, Malaysia, in 2003 to 2005, on the basis of
nucleotide sequences of protease and reverse transcriptase regions. In addition
to circulating HIV-1 strains, including CRF01_AE (57.1%), subtype B (20.1%), and
subtype C (0.5%), we detected a candidate with a new circulating recombinant form
(CRF). We determined four near-full-length nucleotide sequences with identical
subtype structure from epidemiologically unlinked individuals of different risk
and ethnic groups. In this chimera, two short subtype B segments were inserted
into the gag-RT region in a backbone of CRF01_AE. The recombinant structure was
distinct from previously identified CRF15_01B in Thailand. In agreement with the
current HIV nomenclature system, this constitutes a novel CRF (CRF33_01B). The
overall prevalence of CRF33_01B is 19.0% (35/184). Although the prevalence of
CRF33_01B is particularly high among injecting drug users (42.0%, 21/50), it is
also detected in a substantial proportion of homo-/bisexual males (18.8%, 3/16)
and heterosexuals (9.8%, 9/92). Moreover, unique recombinant forms composed of
CRF01_AE and subtype B that have a significant structural relationship with
CRF33_01B were detected in 1.6% (3/184) of study subjects, suggesting an ongoing
recombination process in Malaysia. This new CRF seems to be bridging viral
transmission between different risk populations in this country.
PMID- 17031321
TI - Integration of antiretroviral treatment within antenatal care in Gauteng
Province, South Africa.
AB - BACKGROUND: Antenatal clinics are a key entry point into HIV treatment and care,
together with interventions to reduce mother-to-child transmission (MTCT).
Further evaluation is needed of interventions linking antenatal with
antiretroviral (ARV) treatment services and effectiveness of triple-ARV regimens
for reducing MTCT in resource-constrained settings. METHODS: Data were gathered
from HIV-infected women attending antenatal care from June 2004 to July 2005 at
Coronation Women and Children Hospital, South Africa. After a patient record
review, interventions were implemented to strengthen service linkages and
integrate ARV treatment within antenatal care. Laboratory investigations were
streamlined, including CD4 cell count testing at the first antenatal visit. MTCT
risk for women initiating ARV treatment is compared with that of women-infant
pairs receiving single-dose nevirapine (sd-NVP). RESULTS: In total, 164 pregnant
women initiated ARV treatment and 863 received sd-NVP. After changes to service
delivery, time-to-treatment initiation was reduced from a median of 56 days to 37
days (P = 0.041). The risk of MTCT for women receiving ARV treatment (5 [4.3%] of
116 women) was lower than for those given sd-NVP (74 [10.7%] of 692 women; P =
0.032). CONCLUSIONS: Strengthening linkages and integrating key components of ARV
treatment within antenatal care reduces time-to-treatment initiation. In this
setting, among women with a high MTCT risk, triple-ARV regimens are effective in
reducing HIV infection in infants.
PMID- 17031322
TI - A new implantable middle ear hearing device for mixed hearing loss: A feasibility
study in human temporal bones.
AB - HYPOTHESIS: To assess the feasibility of a new, active middle ear device in
temporal bones (TB). BACKGROUND: This device is designed for patients with mixed
hearing loss subsequent to chronic middle ear infection, surgery, or trauma. This
Bell-Vibroplasty is built from a VIBRANT MED-EL Vibrant Soundbridge and a Kurz
Bell titanium partial ossicular replacement prosthesis. METHODS: In three fresh
TBs, healthy and reconstructed middle ears were analyzed by means of laser
Doppler interferometry. The sound transmission properties of a partial ossicular
replacement prosthesis and a passive and an active Bell-Vibroplasty were compared
with healthy middle ear function. RESULTS: The measurements provided reliable
results with small standard deviations and good signal-to-noise ratios. The
performance levels of the partial ossicular replacement prosthesis and of the
passive Bell-Vibroplasty were comparable with that of healthy middle ear
function. The activated Bell-Vibroplasty provided linear function and a flat
frequency response within the measured frequency range (500 Hz-8 kHz), with peak
deviations of less than 10 dB. The maximum output of the Bell-Vibroplasty was
equivalent to 125-dB sound pressure level. CONCLUSION: Bell-Vibroplasty is
feasible in TBs. Bell-Vibroplasty performance in TBs is sufficient to allow for a
clinical trial as a next step.
PMID- 17031323
TI - The radiographic prevalence of geniculate ganglion dehiscence in normal and
congenitally thin temporal bones.
AB - OBJECTIVE: To determine the prevalence of a dehiscent geniculate ganglion on
routine temporal bone computed tomography (CT). STUDY DESIGN: Retrospective case
review. SETTING: Tertiary referral center. PATIENTS: Two hundred seventy-eight
consecutive temporal bone CT examinations for a total of 556 sides were reviewed.
One hundred ninety-one sides were excluded. Reasons for exclusion included
reconstructed coronal views, no coronal views, or a pathologic process, which
involved the geniculate ganglion. Six examinations were from patients with
clinical superior canal dehiscence confirmed by surgical repair or positive
vestibular evoked myogenic potentials. Twenty-four scans were from patients with
radiographic superior canal dehiscence confirmed by two independent readings.
MAIN OUTCOME MEASURES: The incidence of geniculate ganglion dehiscence in
patients with and without radiographic or clinical superior canal dehiscence.
Dehiscent geniculate ganglion was defined as at least two consecutive cuts on a
coronal CT showing no bone overlying the geniculate ganglion. RESULTS: The
overall incidence of a dehiscent geniculate ganglion was 14.5% in the 365 sides
reviewed. The incidence of a dehiscent geniculate ganglion is increased in
patients with radiographic and clinical superior canal dehiscence as compared
with normal patients and was significantly different by chi analysis (38.1 versus
11.4%). CONCLUSION: The presence of radiographic geniculate ganglion dehiscence
is common. This finding has particular importance when the middle cranial fossa
or subtemporal approach is used, as the facial nerve is more at risk especially
when used to address superior canal dehiscence.
PMID- 17031324
TI - Infective causes of facial nerve paralysis.
AB - OBJECTIVE: To review the functional recovery in a cohort of patients with facial
nerve paralysis (FNP) due to infective cause. STUDY DESIGN: Retrospective review
based on patients identified from a prospectively maintained database of patients
with FNP. The case notes of identified patients were reviewed. SETTING: Tertiary
referral center. PATIENTS: The patients were identified from a database of 1074
patients with FNP. One hundred twenty of the 150 patients identified as having
FNP due to an infectious disease caused by herpes zoster oticus were excluded
from the study. The remaining 30 patients were included in the study.
INTERVENTIONS: Patients were treated both operatively and nonoperatively.
Operative treatment included myringotomy and ventilation tube placement, cortical
mastoidectomy, modified radical (canal wall down) mastoidectomy, petrous
apicectomy, and lateral temporal bone resection. MAIN OUTCOME MEASURES: This
study used the House-Brackmann (HB) grade of facial function at 1 year after
initial assessment. The patients were identified from a prospectively maintained
database of all patients presenting with FNP to a single specialist
otolaryngologist (G.R.C.) between June 1988 and April 2005. The database contains
information including demographic details, dates of presentation, diagnostic
modalities used, diagnosis, interventions, and HB grade. The patients in this
series presented between August 4, 1989 and August 26, 2003. RESULTS: Twenty-nine
patients with 30 facial nerve paralyses were identified. The causes of FNP were
acute otitis media (n = 10); cholesteatoma (n = 10 [acquired, 7; congenital, 3]);
mastoid cavity infections (n = 2); malignant otitis externa (n = 2);
noncholesteatomatous chronic suppurative otitis media (CSOM; n = 2); tuberculous
mastoiditis (n = 1); suppurative parotitis (n = 1); and chronic granulomatosis (n
= 1). The patients with noncholesteatomatous CSOM who presented sooner after the
onset of facial nerve symptoms had greater facial nerve recovery when assessed
using the HB grade at 1 year. CONCLUSION: FNP due to infective causes other than
herpes zoster oticus is rare. Patients with noncholesteatomatous CSOM and FNP
have a better outcome than those with FNP due to cholesteatoma. Patients with FNP
due to acute otitis media tend to have a good prognosis without surgical
decompression of the facial nerve being required.
PMID- 17031325
TI - Effects of a nitric oxide synthase Type II inhibitor on compound action potential
thresholds in experimental endolymphatic hydrops.
AB - HYPOTHESIS: Nitric oxide (NO) is likely to be synthesized by nitric oxide
synthase Type II (NOS II) action and may partake in the origin of changes of
compound action potential (CAP) threshold observed in guinea pigs with induced
endolymphatic hydrops. This study aimed to assess the action of a NOS II
inhibitor on CAP thresholds in these experimental samples. BACKGROUND: In guinea
pigs with experimental endolymphatic hydrops, there are lesions on the cochlea
and progressive increase of CAP threshold. NOS II was found in the cochlea of
this animal model, and it was inferred that NO can contribute by such
alterations. METHODS: The animals were divided into two groups, in which eight
received an intake of a NOS II inhibitor, aminoguanidine, and another eight
served as a control group. During 16 weeks, CAP thresholds at 1,000, 2,000, 4,000
and 6,000 on electrocochleography were compared between the groups. RESULTS: The
group that had an intake of aminoguanidine showed a lower increase on CAP
thresholds at 2,000 (p < 0.05) and 6,000 Hz (p < 0.05) at the 12th postoperative
week, and at 1,000 (p < 0.05), 2,000 (p < 0.001), 4,000 (p < 0.001), > and 6,000
Hz (p < 0.001) at the 16th week. CONCLUSION: We conclude that NOS II inhibitor
reduced the elevation of CAP thresholds in experimentally induced endolymphatic
hydrops.
PMID- 17031326
TI - Dental charity work--does it really help?
PMID- 17031327
TI - A powerful stance.
PMID- 17031328
TI - Competency based surgery.
PMID- 17031329
TI - Fee-splitting.
PMID- 17031330
TI - Supplying demand.
PMID- 17031331
TI - Catastrophic occlusion.
PMID- 17031332
TI - The Pareto principle.
PMID- 17031340
TI - Urgent attention needed for Filipino children.
PMID- 17031343
TI - Amazonian dental adventure.
PMID- 17031342
TI - Dentists increase earnings from private work.
PMID- 17031344
TI - Impression techniques for implant dentistry.
AB - The object of making an impression in implant dentistry is to accurately relate
an analogue of the implant or implant abutment to the other structures in the
dental arch. This is affected by use of an impression coping which is attached to
the implant or implant abutment. This impression coping is incorporated in an
impression - much as a metal framework is 'picked up' in a remount impression for
fixed prosthodontics. With implant copings the coping is usually attached to the
implant or abutment with screws. The impression material used is usually an
elastomeric impression material; the two types most widely used and shown to be
the most appropriate are polyether and polyvinyl siloxane impression materials.
PMID- 17031351
TI - The effect of social demographic factors, snack consumption and vending machine
use on oral health of children living in London.
AB - OBJECTIVE: To investigate the effect of socio-economic status, sugar, snack
consumption and vending machine use on the prevalence and severity of caries
(DMF) in children. DESIGN: An observational study was carried out in a dental
practice in inner city London. Sixty children were asked to complete a
questionnaire and a three day food and drink diary. After a dental examination
the number of decayed (D), missing (M) or filled (F) teeth provided a DMF score.
Anova and Pearsons correlations were used to analyse the data statistically.
RESULTS: Children from social groups I and II consumed significantly less (P <
0.05) sugar, confectionery, crisps and used a vending machine less often than
children from other social groups. Children from Social groups I, II and III had
significantly lower DMF scores. The average DMF from social group I children was
0.5 +/- 0.6, whilst group IV children had the greatest incidence and a DMF of 4.6
+/- 0.8. Significant correlations were identified between DMF and sugar,
confectionery and crisp consumption and vending machine use, and a negative
correlation between DMF and vegetable consumption. CONCLUSIONS: Socio-economic
status and access to vending machines were found to have a significant effect on
sugar intakes, foods choices, and dental health. The removal of vending machines
from schools or at least installing 'healthy' vending machines is recommended.
Health promotion programmes that account for social groups and snacking habits
that are cost effective are required.
PMID- 17031352
TI - Erosion of enamel by non-carbonated soft drinks with and without toothbrushing
abrasion.
AB - OBJECTIVE: To investigate how enamel loss due to erosion, and due to cycling of
erosion and abrasion, depends on compositional parameters of soft drinks, and
particularly whether the thickness of the erosive softened layer is a function of
drink composition. SETTING: University dental hospital research laboratory in the
UK, 2004. MATERIALS AND METHODS: Six drinks were chosen based on their popularity
and composition: apple juice, orange juice, apple drink, orange drink, cranberry
drink and 'ToothKind' blackcurrant drink. Group A samples (n = 36) were exposed
to soft drinks at 36 degrees C for six consecutive 10 minute periods. Group B
samples (n = 36) were subjected to alternating erosion and toothbrushing,
repeated six times. Enamel loss was measured using optical profilometry. RESULTS:
Group A: significant enamel loss was seen for all drinks (p < 0.001). Erosion was
correlated with pH and calcium concentration but not phosphate concentration or
titratable acidity. Group B: significant additional material loss due to
toothbrush abrasion occurred with all drinks. Abrasive enamel loss differed
between the drinks and was positively correlated with drink erosive potential.
CONCLUSION: Enamel loss by erosion is exacerbated by subsequent abrasion. The
amount of softened enamel removed by toothbrushing is a function of the chemical
composition of the erosive medium.
PMID- 17031353
TI - Sedation in Wales: a questionnaire.
AB - AIM: To identify the current provision of sedation in primary dental care in
Wales. DESIGN: Postal questionnaire survey. SETTING: Wales 2003. SUBJECTS AND
MATERIALS: Questionnaires were sent to all dentists appearing on the Dentists
Register with addresses in Wales (n = 1374). The questionnaires sought details on
personal status, use of and training in conscious sedation techniques. RESULTS:
In total 951 (69%) questionnaires were returned, 720 (90%) respondents worked in
a primary dental care setting. Only 87 (12.1%) primary care dentists offered some
form of sedation. CONCLUSIONS: The provision of conscious sedation services in
primary dental care in Wales is poor.
PMID- 17031354
TI - Archaeological evidence for dental innovation: an eighteenth century porcelain
dental prosthesis belonging to Archbishop Arthur Richard Dillon.
AB - During archaeological investigation by Gifford of St Pancras Old Church burial
ground, on the eastern edge of Somers Town, London, in advance of construction of
the new London terminus for the Channel Tunnel Rail Link, a full porcelain
denture was discovered. The high quality porcelain dentures, manufactured in the
late eighteenth century French style, may have been brought with their owner,
Archbishop Arthur Richard Dillon, on his journey into exile. There is evidence of
prolonged use, not only for cosmetic or vocal functions but also in mastication.
The dentures are unique archaeological artefacts and represent a pivotal time in
dental history, with the adoption of new materials and methods of manufacture.
They reflect a period of significant social and economic change for the upper
echelons of French society. This paper outlines the development of porcelain
dentures, discusses the prosthesis, their owner, and a possible provenance.
PMID- 17031368
TI - Dentistry--thinking outside the box.
AB - For Liz Robb, returning to the UK after 25 years away meant a return to the
dental career she thought she'd long since left behind. Here she explains how a
chance look at an advertisement led her to a course that would broaden her
outlook and give her the opportunity to progress in ways she never thought
possible.
PMID- 17031369
TI - Subspecialty certification in urology: a US perspective.
PMID- 17031370
TI - Determining the prognosis of patients with renal cell carcinoma: is it time for a
re-evaluation?
PMID- 17031371
TI - Can TRUS guidance reduce the incidence of positive margins during laparoscopic
radical prostatectomy?
PMID- 17031372
TI - PSA level changes over time in men with an initial PSA level of < or = 4 ng/ml.
PMID- 17031373
TI - Individualized assessment of prostate cancer risk.
PMID- 17031374
TI - Early markers of metabolic syndrome in nonoverweight, middle-aged men.
PMID- 17031375
TI - Improving cancer detection by prostate biopsy: the role of core number and site.
PMID- 17031376
TI - Testosterone levels in benign prostatic hyperplasia: sexual function and response
to therapy with dutasteride.
PMID- 17031377
TI - Are bladder cancer patients with pT0 disease following radical cystectomy cured
of cancer?
PMID- 17031378
TI - Interpreting the international trends in testicular seminoma and nonseminoma
incidence.
AB - There are considerable geographic, ethnic and temporal variations in the global
incidence of testicular cancer. The disease mainly affects Western populations,
with average rates in developed areas of the world six times higher than those in
developing areas. About 500,000 new cases were diagnosed worldwide in 2002, with
the vast majority being germ cell tumors and occurring in young adult males.
Traditionally, these tumors are further classified into seminoma and nonseminoma.
In this Review, trends in the incidence of germ cell tumors are examined using
high-quality cancer-registry data from 41 populations within 14 countries
worldwide. To assess whether trends of seminoma and nonseminoma incidence are
similar, data were analyzed by birth cohort. These analyses should reveal similar
trends if the 10-year difference in the clinical manifestation of cancer between
subtypes is caused by differences in the speed of progression from the same early
rate-limiting step to the onset of symptomatic disease. In each country,
incidence has uniformly increased in successive generations born from around 1920
until very recently. Cohort-specific trends in seminoma incidence are similar to
cohort-specific trends in nonseminoma incidence, lending support to the
conclusion that the subtypes are epidemiologically and etiologically comparable.
The findings presented are related to current theories and evidence regarding the
determinants of testicular germ cell cancer.
PMID- 17031379
TI - Recommendations for urodynamic assessment in the evaluation of women with stress
urinary incontinence.
AB - Urinary incontinence is a common problem that is experienced by women of all
ages. The overall evaluation and treatment of incontinence has increased in
sophistication, both as a result of the introduction of urodynamic testing in the
assessment of patients, and because there are increasing numbers of medical and
surgical treatments available for incontinence. What was previously considered a
personal problem for women, and which was rarely discussed, has become a more
open and acceptable complaint for female patients to bring to their physicians.
This Review aims to clarify when urodynamic testing is clearly indicated for
patients with symptoms of stress urinary incontinence, and describes the current
recommendations from three national and international governing bodies. This
Review will also highlight some of the ongoing debates over the performance,
interpretation, and utility of urodynamic testing, and provide references for
further reading on these topics.
PMID- 17031380
TI - Primer: diagnosis and management of uncomplicated daytime wetting in children.
AB - Functional daytime wetting is a common source of pediatric urologic complaints.
Evaluation typically begins in the office setting. In contrast to the adult
population, where an inability to maintain voiding control is virtually always
considered pathologic, the evaluation of urinary incontinence in children must
occur within the context of the child's developmental age. Functional
incontinence refers to cases of urinary incontinence in which no structural or
neurologic abnormality can be identified. The underlying etiologic mechanisms are
heterogeneous, and include disorders of both the storage and voiding phases of
the bladder cycle. Optimal treatment of functional daytime wetting depends on an
accurate determination of the underlying etiology. Therapeutic options include
behavior modification, medication, and aggressive treatment of comorbid
conditions such as urinary infection and constipation.
PMID- 17031381
TI - Hypogonadotropism with elevated serum testosterone: reversible causes of
secondary infertility.
AB - BACKGROUND: A 33-year-old man presented with secondary infertility, increased
libido, and extreme oligospermia. Testicular volumes were reduced, but no
gynecomastia was apparent and androgen abuse was denied. INVESTIGATIONS: Physical
examination, semen-volume and sperm-density assessment, laboratory tests for
serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone,
and dehydroepiandrosterone sulfate, karyotyping, testicular ultrasound, pelvic
and abdominal CT, assessment for serum testicular tumor markers (alpha
fetoprotein and human chorionic gonadotropin), and histologic examination of
testicular tissue. DIAGNOSIS: Benign Leydig-cell adenoma. MANAGEMENT: Left
orchidectomy.
PMID- 17031382
TI - Species and response dependent differences in the effects of MAPK inhibitors on
P2X(7) receptor function.
AB - BACKGROUND: Recent studies have implicated the mitogen activated protein kinase
(MAPK) in cellular permeability changes following P2X(7) receptor activation in
native tissues. In this study we have further studied the effect of MAPK
inhibitors on recombinant and native P2X(7) receptors. EXPERIMENTAL APPROACH: The
MAPK inhibitors SB-203580, SB-202190 and SB-242235 were examined in HEK293 cells
expressing recombinant P2X(7) receptors and in THP-1 cells expressing native
human P2X(7) receptors using a range of experimental approaches. KEY RESULTS: At
human recombinant P2X(7) receptors, SB-203580 and SB-202190 were weak, non
competitive inhibitors (pIC(50)= 4.8 - 6.4) of ethidium accumulation stimulated
by 2'- & 3'-O-(4benzoylbenzoyl)-ATP (BzATP) but SB-242235 (0.1-10 microM) had no
effect. SB-203580 and SB-202190 had no effect on rat or mouse recombinant P2X(7)
receptors and studies with chimeric P2X(7) receptors suggested that SB-203580 was
only effective in chimeras containing the N-terminal 255aa of the human P2X(7)
receptor. SB-203580 did not consistently affect BzATP-mediated increases in cell
calcium levels and, in electrophysiological studies, it slightly decreased
responses to 30 microM BzATP but potentiated responses to 100 microM BzATP. In
THP1 cells, SB-203580 modestly inhibited BzATP-stimulated ethidium accumulation
(pIC(50) 5.7 - < 5) but SB-202190 had no effect. Finally, SB-203580 did not block
BzATP-stimulated interleukin-1beta release in THP-1 cells. CONCLUSIONS: This
study confirms that high concentrations of SB-203580 and SB-202190 can block
human P2X(7) receptor-mediated increases in cellular ethidium accumulation but
suggest this is not related to MAPK inhibition. Overall, the data cast doubt on a
general role of MAPK in mediating P2X(7) receptor mediated changes in cellular
permeability.
PMID- 17031383
TI - Mechanisms underlying lysophosphatidylcholine-induced potentiation of vascular
contractions in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat aorta.
AB - BACKGROUND AND PURPOSE: The effect of lysophosphatidylcholine (LPC) on aortic
contractions in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic
model, was studied. EXPERIMENTAL APPROACH: Using OLETF rats and control (Long
Evans Tokushima Otsuka (LETO)) rats, the effects of LPC on the contractions
induced by high-K(+) (10-40 mM), UK14,304 (10 approximately 100 nM; a selective
alpha(2)-adrenoceptor agonist) and sodium orthovanadate (SOV; 10 microM
approximately 3 mM) in endothelium-denuded aortae were compared. Aortic ERK
activity and the mRNA expression for GPR4 (a putative LPC receptor) were also
measured. KEY RESULTS: OLETF rats exhibited (vs. age-matched LETO rats): (1)
greater potentiation of high-K(+)-induced contraction by 10 microM LPC - a
potentiation attenuated by 10 microM genistein, protein tyrosine kinase (PTK)
inhibitor, (2) greater potentiation of UK14,304 (10 approximately 100 nM)-induced
contractions by LPC (1 microM approximately 10 microM) - a potentiation
attenuated by 10 microM genistein, 50 microM tyrphostin A23 (PTK inhibitor) or 10
microM PD98059 (MEK 1/2 inhibitor), (3) greater basal and LPC (1 microM)-induced
ERK activities, (4) greater basal and 100 nM UK14,304-stimulated ERK2 activities
in both the absence and presence of 10 microM LPC, (5) greater SOV (10 microM
approximately 3 mM)-induced contractions, (6) greater potentiation of SOV-induced
contractions by 10 microM LPC - a potentiation suppressed by 10 microM PD98059 or
10 microM genistein, (7) upregulation of GPR4 mRNA. CONCLUSIONS AND IMPLICATIONS:
These results suggest that the LPC-induced potentiation of contractions in the
OLETF rat aorta may be attributable to increased PTKs or ERK activity and/or to
receptor upregulation.
PMID- 17031384
TI - Mitochondria, the calcium uniporter, and reperfusion-induced ventricular
fibrillation.
AB - The role of the mitochondria, and in particular the calcium (Ca) uniporter, in
mediating reperfusion-induced arrhythmias is a novel investigative area. This
commentary assesses the importance of a new article on this topic, published in
this issue of the journal. Ventricular arrhythmogenesis remains an important area
of research in the search of novel targets. The article by Garcia-Rivas et al in
this issue represents a possible novel focus for investigation.
PMID- 17031385
TI - Characterization of a selective and potent antagonist of human P2X(7) receptors,
AZ11645373.
AB - BACKGROUND AND PURPOSE: The ATP-gated P2X(7) receptor has been shown to play a
role in several inflammatory processes, making it an attractive target for anti
inflammatory drug discovery. We have recently identified a novel set of cyclic
imide compounds that inhibited P2X(7) receptor-mediated dye uptake in human
macrophage THP-1 cells. In this study the actions and selectivity of one of these
compounds, AZ11645373, were characterized. EXPERIMENTAL APPROACH: We measured
membrane currents, calcium influx, and YOPRO-1 uptake from HEK cells expressing
individual P2X receptors, and YOPRO1 uptake and interleukin-1beta release from
THP-1 cells in response to ATP and the ATP analogue benzoylbenzoyl ATP (BzATP).
KEY RESULTS: AZ11645373 up to 10 microM, had no agonist or antagonist actions on
membrane currents due to P2X receptor activation at human P2X(1), rat P2X(2),
human P2X(3), rat P2X(2/3), human P2X(4), or human P2X(5) receptors expressed in
HEK cells. AZ11645373 inhibited human P2X(7) receptor responses in HEK cells in a
non-surmountable manner with K (B) values ranging from 5 - 20 nM, with mean
values not significantly different between assays. K (B) values were not altered
by removing extracellular calcium and magnesium. ATP-evoked IL-1beta release from
lipopolysaccharide-activated THP-1 cells was inhibited by AZ11645373, IC(50) = 90
nM. AZ11645373 was > 500-fold less effective at inhibiting rat P2X(7) receptor
mediated currents with less than 50% inhibition occurring at 10 microM.
CONCLUSIONS AND IMPLICATIONS: AZ11645373 is a highly selective and potent
antagonist at human but not rat P2X(7) receptors and will have much practical
value in studies of human cells.
PMID- 17031386
TI - Ru360, a specific mitochondrial calcium uptake inhibitor, improves cardiac post
ischaemic functional recovery in rats in vivo.
AB - BACKGROUND AND PURPOSE: The mitochondrial permeability transition pore (mPTP), an
energy-dissipating channel activated by calcium, contributes to reperfusion
damage by depolarizing the mitochondrial inner membrane potential. As
mitochondrial Ca(2+) overload is a main inductor of mPTP opening, we examined the
effect of Ru(360), a selective inhibitor of the mitochondrial calcium uptake
system against myocardial damage induced by reperfusion in a rat model.
EXPERIMENTAL APPROACH: Myocardial reperfusion injury was induced by a 5-min
occlusion of the left anterior descending coronary artery, followed by a 5-min
reperfusion in anaesthetized open-chest rats. We measured reperfusion-induced
arrhythmias and functions indicative of unimpaired mitochondrial integrity to
evaluate the effect of Ru(360) treatment. KEY RESULTS: Reperfusion elicited a
high incidence of arrhythmias, haemodynamic dysfunction and loss of mitochondrial
integrity. A bolus intravenous injection of Ru(360) (15-50 nmol kg(-1)), given 30
min before ischaemia, significantly improved the above mentioned variables in the
ischaemic/reperfused myocardium. Calcium uptake in isolated mitochondria from
Ru(360)-treated ventricles was partially diminished, suggesting an interaction of
this compound with the calcium uniporter. CONCLUSIONS AND IMPLICATIONS: We showed
that Ru(360) treatment abolishes the incidence of arrhythmias and haemodynamic
dysfunction elicited by reperfusion in a whole rat model. Ru(360) administration
partially inhibits calcium uptake, preventing mitochondria from depolarization by
the opening of the mPTP. We conclude that myocardial damage could be a
consequence of failure of the mitochondrial network to maintain the membrane
potential at reperfusion. Hence, it is plausible that Ru(360) could be used in
reperfusion therapy to prevent the occurrence of arrhythmia.
PMID- 17031387
TI - Iron is not involved in oxidative stress-mediated cytotoxicity of doxorubicin and
bleomycin.
AB - BACKGROUND AND PURPOSE: The anticancer drugs doxorubicin and bleomycin are well
known for their oxidative stress-mediated side effects in heart and lung,
respectively. It is frequently suggested that iron is involved in doxorubicin and
bleomycin toxicity. We set out to elucidate whether iron chelation prevents the
oxidative stress-mediated toxicity of doxorubicin and bleomycin and whether it
affects their antiproliferative/proapoptotic effects. EXPERIMENTAL APPROACH: Cell
culture experiments were performed in A549 cells. Formation of hydroxyl radicals
was measured in vitro by electron paramagnetic resonance (EPR). We investigated
interactions between five iron chelators and the oxidative stress-inducing agents
(doxorubicin, bleomycin and H(2)O(2)) by quantifying oxidative stress and
cellular damage as TBARS formation, glutathione (GSH) consumption and lactic
dehydrogenase (LDH) leakage. The antitumour/proapoptotic effects of doxorubicin
and bleomycin were assessed by cell proliferation and caspase-3 activity assay.
KEY RESULTS: All the tested chelators, except for monohydroxyethylrutoside
(monoHER), prevented hydroxyl radical formation induced by H(2)O(2)/Fe(2+) in EPR
studies. However, only salicylaldehyde isonicotinoyl hydrazone and deferoxamine
protected intact A549 cells against H(2)O(2)/Fe(2+). Conversely, the chelators
that decreased doxorubicin and bleomycin-induced oxidative stress and cellular
damage (dexrazoxane, monoHER) were not able to protect against H(2)O(2)/Fe(2+).
CONCLUSIONS AND IMPLICATIONS: We have shown that the ability to chelate iron as
such is not the sole determinant of a compound protecting against doxorubicin or
bleomycin-induced cytotoxicity. Our data challenge the putative role of iron and
hydroxyl radicals in the oxidative stress-mediated cytotoxicity of doxorubicin
and bleomycin and have implications for the development of new compounds to
protects against this toxicity.
PMID- 17031391
TI - The effect of 6 months supplementation with conjugated linoleic acid on insulin
resistance in overweight and obese.
AB - BACKGROUND: Contradicting results have been published regarding the effect of
conjugated linoleic acid (CLA) on insulin resistance. However, only a few studies
have used the euglycemic hyperinsulinemic clamp method, which is considered the
standard for measuring insulin resistance. OBJECTIVE: To evaluate if CLA as a
mixture of the main isomers trans-10 cis-12 and cis-9 trans-11 affects the
insulin resistance in healthy overweight and obese male and female adults.
DESIGN: The main study was a randomized, double-blind, placebo-controlled trial
with change in body composition as primary end point comprising 118 subjects
receiving supplementation with either placebo (olive oil) or CLA (Clarinol) for 6
months. A sub-population of 49 subjects agreed additionally to participate in an
euglycemic hyperinsulinemic clamp study at baseline and after 6 months of
supplementation with study drug. The primary outcome was the change in glucose
uptake (M) as measured by the hyperinsulinemic euglycemic glucose clamp method.
Secondary outcomes were the correlates between insulin resistance and changes in
body composition or blood chemistry parameters. Forty-one subjects completed the
clamp test at both time points. RESULTS: The median M of the CLA group was 11.0
mg min(-1) lean body mass (lbm)(-1) (n=24) at baseline, 10.3 mg min(-1) lbm(-1)
(n=24) after 6 months, and the median difference was +0.21 mg min(-1) lbm(-1)
(n=24). The median M of placebo group was 8.4 mg min(-1) lbm(-1) at baseline and
9.3 mg min(-1) lbm(-1) after 6 months and the median difference was -0.22 mg min(
1) lbm(-1) (n=17). No significant (P<0.05) differences were found within groups
or between groups. Likewise, the glucose uptake insulin concentration ratio
during clamp (M/I) was independent of treatment and time. Homeostasis model
assessment (HOMA) and quantitative insulin sensitivity check index derived from
fasting glucose and insulin were also independent of treatment and time, and HOMA
for the clamp population (n=49) corresponded well with HOMA for the per protocol
population (n=83). Correlation analysis showed that changes in M were inversely
correlated to changes in glucohemoglobin (P=0.002), but did not correlate with
changes in either glucose, insulin, insulin c-peptide, leptin, adiponectin or
percent body fat. CONCLUSIONS: CLA does not affect glucose metabolism or insulin
sensitivity in a population of overweight or obese volunteers.
PMID- 17031388
TI - Effects of chronic treatment with statins and fenofibrate on rat skeletal muscle:
a biochemical, histological and electrophysiological study.
AB - BACKGROUND AND PURPOSE: Skeletal muscle injury by hypolipidemic drugs is not
fully understood. An extensive analysis of the effect of chronic treatment with
fluvastatin (5 mgkg(-1) and 20 mgkg(-1)), atorvastatin (10 mgkg(-1)) and
fenofibrate (60 mgkg(-1)) on rat skeletal muscle was undertaken. EXPERIMENTAL
APPROACH: Myoglobinemia as sign of muscle damage was measured by enzymatic assay.
Histological and immunohistochemical techniques were used to estimate muscle
integrity and the presence of aquaporin-4, a protein controlling water
homeostasis. Electrophysiological evaluation of muscle Cl(-) conductance (gCl)
and mechanical threshold (MT) for contraction, index of intracellular calcium
homeostasis, was performed by the two-intracellular microelectrodes technique.
KEY RESULTS: Fluvastatin (20 mgkg(-1)) increased myoglobinemia. The lower dose of
fluvastatin did not modify myoglobinemia, but reduced urinary electrolytes,
suggesting direct effects on renal function. Atorvastatin also increased
myoglobinemia, with slight effects on urinary parameters. No treatment caused any
histological damage to muscle or modification in the number of fibres expressing
aquaporin-4. Either fluvastatin (at both doses) or atorvastatin reduced
sarcolemma gCl and changed MT. Both statins produced slight effects on total
cholesterol, suggesting that the observed modifications occur independently of
HMGCoA-reductase inhibition. Fenofibrate increased myoglobinemia and decreased
muscle gCl, whereas it did not change the MT, suggesting a different mechanism of
action from the statins. CONCLUSIONS AND IMPLICATIONS: This study identifies
muscle gCl and MT as early targets of drugs action that may contribute to milder
symptoms of myotoxicity, such as muscle cramps, while the increase of
myoglobinemia is a later phenomenon.
PMID- 17031389
TI - A rabbit Langendorff heart proarrhythmia model: predictive value for clinical
identification of Torsades de Pointes.
AB - BACKGROUND AND PURPOSE: The rabbit isolated Langendorff heart model (SCREENIT)
was used to investigate the proarrhythmic potential of a range of marketed drugs
or drugs intended for market. These data were used to validate the SCREENIT model
against clinical outcomes. EXPERIMENTAL APPROACH: Fifty-five drugs, 3 replicates
and 2 controls were tested in a blinded manner. Proarrhythmia variables included
a 10% change in MAPD(60), triangulation, instability and reverse frequency
dependence of the MAP. Early after-depolarisations, ventricular tachycardia, TdP
and ventricular fibrillation were noted. Data are reported at nominal
concentrations relative to EFTPC(max). Proarrhythmic scores were assigned to each
drug and each drug category. KEY RESULTS: Category 1 and 2 drugs have the highest
number of proarrhythmia variables and overt proarrhythmia while Category 5 drugs
have the lowest, at every margin. At 30-fold the EFTPC(max), the mean
proarrhythmic scores are: Category 1, 101+/-24; Category 2, 101+/-14; Category 3,
72+/-20; Category 4, 59+/-16 and Category 5, 22+/-9 points. Only drugs in
Category 5 have mean proarrhythmic scores, below 30-fold, that remain within the
Safety Zone. CONCLUSIONS AND IMPLICATIONS: A 30-fold margin between effects and
EFTPC(max) is sufficiently stringent to provide confidence to proceed with a new
chemical entity, without incurring the risk of eliminating potentially beneficial
drugs. The model is particularly useful where compounds have small margins
between the hERG IC(50) and predicted EFTPC(max). These data suggest this is a
robust and reliable assay that can add value to an integrated QT/TdP risk
assessment.
PMID- 17031392
TI - Hemicentins: what have we learned from worms?
AB - Hemicentins are conserved extracellular matrix proteins discovered in
Caenorhabditis elegans, with orthologs in all vertebrate species including human
and mouse. Hemicentins share a single, highly conserved amino-terminal von
Willebrand A domain, followed by a long (>40) stretch of immunoglobulin repeats,
multiple tandem epidermal growth factors and a fibulin-like carboxy-terminal
module. C. elegans has a single hemicentin gene that has pleiotropic functions in
transient cell contacts that are required for cell migration and basement
membrane invasion and in stable contacts at hemidesmosome-mediated cell junctions
and elastic fiber-like structures. Here, we summarize what is known about the
function of hemicentin in C. elegans and discuss implications for hemicentin
function in other species.
PMID- 17031393
TI - Transgenic expression of DwMYB2 impairs iron transport from root to shoot in
Arabidopsis thaliana.
AB - In plant, iron uptake and homeostasis are tightly regulated to ensure its
absorption from soil and to avoid excess iron in the cell. Many genes involved in
this process have been identified during past several years, but there are many
problems remain unsolved in the genetic regulation of whole plant iron
trafficking and allocation. MYB transcription factors contain tandem repeats of a
approximately 50 amino acid DNA-binding motif (R) and are involved in the
regulation of many aspects of plant development, hormone signaling and
metabolism. Here, we report that the ectopic expression of orchid R2R3-MYB gene
DwMYB2 in Arabidopsis thaliana confers the transgenic plants hypersensitivity to
iron deficiency. In DwMYB2 transgenic plants, the iron content in root is two
fold higher compared to that in wild-type root, while the reverse is true in
shoot. This imbalance of iron content in root and shoot suggested that the
translocation of iron from root to shoot was affected by the expression of DwMYB2
in the transgenic plants. Consistently, gene chip and reverse transcription
polymerase chain reaction analysis revealed that the ferric-chelate reductase
gene, AtFRO2, and the iron transporter gene, AtIRT1 and AtIRT2, are up-regulated
by DwMYB2 expression, while other potential iron transporters such as AtIREG1,
AtFRD3 and NRAMP1 are down-regulated. In addition, the expression of several
putative peptide transporters and transcription factors are also altered in the
35S::DwMYB2 transgenic lines. These data provide us insight into the whole plant
translocation of iron and identify candidate genes for iron homeostasis in plants
despite the fact that a heterologous gene was expressed.
PMID- 17031394
TI - Second primary cancer in survivors following concurrent chemoradiation for
locally advanced non-small-cell lung cancer.
AB - Long-term cancer survivors risk development of second primary cancers (SPC).
Vigilant follow-up may be required. We report outcomes of 92 patients who
underwent chemoradiation for unresectable stage III non-small-cell lung cancer,
with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100
patient-years (95% confidence interval: 1.0-4.9).
PMID- 17031395
TI - The role of MYH and microsatellite instability in the development of sporadic
colorectal cancer.
AB - Biallelic germline mutations in MYH are associated with colorectal neoplasms,
which develop through a pathway involving somatic inactivation of APC. In this
study, we investigated the incidence of the common MYH mutations in an Australian
cohort of sporadic colorectal cancers, the clinicopathological features of MYH
cancers, and determined whether inactivation of mismatch repair and base excision
repair (BER) were mutually exclusive. The MYH gene was sequenced from lymphocyte
DNA of 872 colorectal cancer patients and 478 controls. Two compound
heterozygotes were identified in the cancer population and all three cancers from
these individuals displayed a prominent infiltration of intraepithelial
lymphocytes. In total, 11 heterozygotes were found in the cancer group and five
in the control group. One tumour from an individual with biallelic germline
mutation of MYH also demonstrated microsatellite instability (MSI) as a result of
biallelic hypermethylation of the MLH1 promoter. Although MYH-associated cancers
are rare in a sporadic colorectal population, this study shows that these tumours
can develop through either a chromosomal or MSI pathway. Tumours arising in the
setting of BER or mismatch repair deficiency may share a biological
characteristic, which promotes lymphocytic infiltration.
PMID- 17031396
TI - Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose
ifosfamide, high-dose doxorubicin and salvage therapies.
AB - Having determined in a phase I study the maximum tolerated dose of high-dose
ifosfamide combined with high-dose doxorubicin, we now report the long-term
results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients
with locally advanced or metastatic soft-tissue sarcomas were included, with age
<60 years and all except one in good performance status (0 or 1). The
chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion
for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna
and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A
median of 4 (1-6) cycles per patient was administered. Twenty-two patients
responded to therapy, including three complete responders and 19 partial
responders for an overall response rate of 48% (95% CI: 33-63%). The response
rate was not different between localised and metastatic diseases or between
histological types, but was higher in grade 3 tumours. Median overall survival
was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in
43% of patients and found to be the most significant predictor for favourable
survival (exploratory multivariate analysis). Haematological toxicity was severe,
including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in
27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient
died of septic shock. This high-dose regimen is toxic but nonetheless feasible in
multicentre settings in non elderly patients with good performance status. A high
response rate was obtained. Prolonged survival was mainly a function of salvage
therapies.
PMID- 17031397
TI - A phase II clinical and pharmacodynamic study of temsirolimus in advanced
neuroendocrine carcinomas.
AB - Standard cytotoxic treatments for neuroendocrine tumours have been associated
with limited activity and remarkable toxicity. A phase II study was designed to
evaluate the efficacy, safety and pharmacodynamics of temsirolimus in patients
with advanced neuroendocrine carcinoma (NEC). Thirty-seven patients with advanced
progressive NEC received intravenous weekly doses of 25 mg of temsirolimus.
Patients were evaluated for tumour response, time to progression (TTP), overall
survival (OS) and adverse events (AE). Twenty-two archival specimens, as well as
13 paired tumour biopsies obtained pretreatment and after 2 weeks of temsirolimus
were assessed for potential predictive and correlative markers. The intent-to
treat response rate was 5.6% (95% CI 0.6-18.7%), median TTP 6 months and 1-year
OS rate 71.5%. The most frequent drug-related AE of all grades as percentage of
patients were: fatigue (78%), hyperglycaemia (69%) and rash/desquamation (64%).
Temsirolimus effectively inhibited the phosphorylation of S6 (P=0.02). Higher
baseline levels of pmTOR (phosphorylated mammalian target of rapamycin) (P=0.01)
predicted for a better response. Increases in pAKT (P=0.041) and decreases in
pmTOR (P=0.048) after treatment were associated with an increased TTP.
Temsirolimus appears to have little activity and does not warrant further single
agent evaluation in advanced NEC. Pharmacodynamic analysis revealed effective
mTOR pathway downregulation.
PMID- 17031398
TI - Survival trends for small intestinal cancer in England and Wales, 1971-1990:
national population-based study.
AB - This population-based study examines prognostic factors and survival trends among
adults (15-99 years) diagnosed with small intestinal cancer in England and Wales
during 1971-1990 and followed up to 1995. During this period, the 1- and 5-year
age-standardised relative survival rates for small intestinal cancers combined
were 42% and 23%, respectively. Duodenal tumours, adenocarcinomas, men, patients
with advanced age and the most deprived patients had the poorest prognosis. For
all small bowel tumours combined, the excess risk of death fell significantly by
6-9% every 4 years over the 20-year period (adjusted excess hazard ratio (EHR)
0.91 at 1 year after diagnosis, 0.94 at 5 years). For duodenal tumours, the EHR
fell by about 14% (95% CI 5-22%) every 4 years between 1979 and 1990, and a
similar trend for jejunal tumours was of borderline significance. Further
population-based investigations linking survival data to individual data on
diagnostic methods and types of treatment are needed.
PMID- 17031399
TI - The significance of the time interval between antecedent pregnancy and diagnosis
of high-risk gestational trophoblastic tumours.
AB - It is thought that the time interval between the antecedent pregnancy and
diagnosis of gestational trophoblastic tumours (GTTs) may influence the outcome
of these patients. In this study, we investigate the significance of this time
interval. Multivariate analysis was used to investigate if the time interval was
of prognostic significance from our cohort of 241 high-risk patients with GTT.
Subsequent cutpoint analysis was used to determine an optimal cutpoint for the
interval covariate. The outcome of these patients was plotted according to the
Kaplan-Meier method. The time interval was of prognostic significance on
multivariate analysis. A period of greater than 2.8 years after pregnancy was
found to be of most significance. The 5-year overall survival was 62.0% (95% CI:
47-76%) for greater than 2.8 years vs 94% (95% CI: 91-97%) for less than 2.8
years (P<0.001). Multivariate analysis showed the presence of liver metastasis
and the number of metastasis was also of prognostic importance. The interval
between antecedent pregnancy and diagnosis in high-risk GTT is of prognostic
significance. This gives some insight into the pathogenesis of the disease.
PMID- 17031401
TI - Incidence rate trends of histological subtypes of nasopharyngeal carcinoma in
Hong Kong.
AB - The overall decline in incidence rate of nasopharyngeal carcinoma in Hong Kong
during 1988-2002 was limited primarily to a decrease in keratinising carcinoma,
which could be explained by the decline in cigarette smoking. Genetic and Epstein
Barr virus interactions may explain the relatively stable incidence rate of non
keratinising carcinoma.
PMID- 17031400
TI - Reduction of mitomycin C is catalysed by human recombinant NRH:quinone
oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron
donating co-factor.
AB - NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic
activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron
donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a
mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2
catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction
results in species that inhibit the NQO2-mediated metabolism of CB1954. In
addition, MMC caused an increase in DNA cross-links in a cell line transfected to
overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1
expressing cell line. These data indicate that NQO2 may contribute to the
metabolism of MMC to cytotoxic species.
PMID- 17031402
TI - A specific cadherin phenotype may characterise the disseminating yet non
metastatic behaviour of pseudomyxoma peritonei.
AB - Pseudomyxoma peritonei (PMP) is a rare neoplasm of mainly appendiceal origin,
characterised by excess intra-abdominal mucin production leading to high
morbidity and mortality. While histological features are frequently indolent,
this tumour disseminates aggressively throughout the abdominal cavity, yet seldom
metastasises. This study determined the expression of several markers of
colorectal differentiation (carcinoembryonic antigen (CEA), cytokeratins (CK20
and CK7), epithelial membrane antigen), mucin production (MUC-2, interleukin-9
(IL-9), IL-9 receptor (IL-9Ralpha)), and cell adhesion (N- and E-cadherin,
vimentin) in PMP tissue (n=26) compared with expressions in normal colonic mucosa
(n=19) and colorectal adenocarcinoma (n=26). Expressions of CEA and cytokeratins
were similar for PMP as those in colorectal adenocarcinomas with the exception
that the CK20-/CK7- pattern was rare in PMP (Fisher's exact test: P=0.001).
Similarly, expressions of mucin-related proteins were comparable for
adenocarcinoma and PMP, with the exception that IL-9 expression was uncommon in
adenocarcinoma (P=0.009). Pseudomyxoma peritonei demonstrated a specific pattern
of adhesion-related protein expressions of increased N-cadherin, reduced E
cadherin, and increased vimentin (P=0.004), a phenotype suggesting a possible
epithelial-mesenchymal transition state. Primary PMP cell cultures were
successfully maintained and demonstrated marker expressions similar to those seen
in in vivo tissues. These early characterisation studies demonstrate similarities
between PMP and colorectal adenocarcinoma, but also reveal a specific cadherin
phenotype that may characterise the distinct non-metastasising behaviour of PMP,
and form the basis for future mechanistic and therapy-targeting research.
PMID- 17031403
TI - Perioperative immunomodulation with interleukin-2 in patients with renal cell
carcinoma: results of a controlled phase II trial.
AB - We conducted a non-randomised controlled phase II trial to investigate the role
of preoperative administration of interleukin-2 (IL-2) in patients with renal
cell carcinoma undergoing tumour nephrectomy. A total of 120 consecutive patients
were allocated alternately to the two study groups: perioperative
immunomodulation with IL-2 (IL-2 group; n=60) and perioperative immunomonitoring
without immunomodulation (control group; n=60). Patients from the IL-2 group
received four doses of 10 x 10(6) IU m(-2) twice daily subcutaneously a week
before operation followed by a daily maintenance dose of 3 x 10(6) IU m(-2)
subcutaneously until a day before the operation. Parameters of cellular and
humoral immunity (leucocytes, T-cell markers CD3, CD4, and CD8, B-cell marker
CD19, monocyte marker CD14, natural killer (NK) cell markers CD16, CD56, and
CD57, activation markers CD6, CD25, CD28, and CD69, progenitor cell marker CD34,
as well as IL-2, IL-6, IL-10, soluble IL-2 receptor, IL-1 receptor antagonist,
transforming growth factor-beta1, and vascular endothelial growth factor) were
measured in peripheral venous blood at various intervals. Interleukin-2-related
toxicity was WHO grade 1 (24%), 2 (67%), and 3 (9%). In the postoperative period,
T-cell markers, activation markers, and NK cell markers decreased, and IL-6 and
IL-10 increased. However, all these alterations were significantly less
accentuated in patients who had been pretreated with IL-2. Median follow-up was
40 months. Tumour-specific survival in the IL-2 group and the control group was
98 vs 81% after 1 year and 86 vs 73% after 5 years (P=0.04). A similar effect was
found for progression-free survival. We conclude that IL-2 can be safely
administered in the perioperative period and modulates immunological parameters.
However, to validate the survival data, a larger randomised phase III trial is
needed.
PMID- 17031404
TI - Genetic and metabolic predictors of chemosensitivity in oligodendroglial
neoplasms.
AB - The -1p/-19q genotype predicts chemosensitivity in oligodendroglial neoplasms,
but some with intact 1p/19q also respond and not all with 1p/19q loss derive
durable benefit from chemotherapy. We have evaluated the predictive and
prognostic significance of pretherapy (201)Tl and (18)F-FDG SPECT and genotype in
38 primary and 10 recurrent oligodendroglial neoplasms following PCV
chemotherapy. 1p/19q loss was seen in 8/15 OII, 6/15 OAII, 7/7 OIII, 3/11 OAIII
and was associated with response (Fisher-Exact: P=0.000) and prolonged
progression-free (log-rank: P=0.002) and overall survival (OS) (log-rank:
P=0.0048). Response was unrelated to metabolism, with tumours with high or low
metabolism showing response. Increased (18)F-FDG or (201)Tl uptake predicted
shorter progression-free survival (PFS) in the series (log-rank: (201)Tl
P=0.0097, (18)F-FDG P=0.0170) and in cases with or without the -1p/-19q genotype.
Elevated metabolism was associated with shorter OS in cases with intact 1p/19q
(log-rank: (18)F-FDG P=0.0077; (201)Tl P=0.0004) and shorter PFS in responders
(log-rank: (18)F-FDG P=0.005; (201)Tl P=0.0132). (201)Tl uptake and 1p/19q loss
were independent predictors of survival in multivariate analysis. In this initial
study, (201)Tl and (18)F-FDG uptake did not predict response to PCV, but may be
associated with poor survival following therapy irrespective of genotype. This
may be clinically useful warranting further study.
PMID- 17031406
TI - Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in
metastatic renal cell carcinoma.
AB - Immunotherapy is the only available treatment for metastatic renal cell cancer
(RCC), but the response rate is only about 20% and the treatment is occasionally
associated with severe adverse effects. Thus, the selection of patients with a
high susceptibility to immunotherapy is needed; however, there is no promising
molecular marker that can predict the response to immunotherapy for RCC. This
study was carried out to elucidate the potential role of apoptosis-related
molecules Bcl-2 and Fas, as well as apoptotic and proliferating indexes (AI, PI)
as predictors of the susceptibility of metastatic RCC to immunotherapy.
Immunohistochemical examination of tumour tissues from 40 patients with
metastatic RCC undergoing postoperative immunotherapy after radical nephrectomy
was performed. Patients with progressive disease (PD) after immunotherapy
presented with decreased survival (P=0.006). Progressive disease correlated with
higher PI in the primary lesion (P=0.0087). All primary tumours of CR or PR
patients were negative for Bcl-2, whereas among NC+PD patients, 40.6% were
positive for Bcl-2 (P=0.0373). Patients in whom the primary tumours were both Bcl
2- and Fas-negative showed significantly better responses to immunotherapy in
comparison with the remaining group (P=0.0022). The Bcl-2 and Fas status of the
primary lesion may become useful criteria for the selection of patients with
metastatic RCC for immunotherapy.
PMID- 17031405
TI - The role of socio-economic status in the decision making on diagnosis and
treatment of oesophageal cancer in The Netherlands.
AB - In the United States (USA), a correlation has been demonstrated between socio
economic status (SES) of patients on the one hand, and tumour histology, stage of
the disease and treatment modality of various cancer types on the other hand. It
is unknown whether such correlations are also involved in patients with
oesophageal cancer in The Netherlands. Between 1994 and 2003, 888 oesophageal
cancer patients were included in a prospective database with findings on the
diagnostic work-up and treatment of oesophageal cancer. Socio-economic status of
patients was defined as the average net yearly income. Linear-by-linear
association testing revealed that oesophageal adenocarcinoma was more frequently
observed in patients with higher SES and squamous cell carcinoma in patients with
lower SES (P=0.02). Multivariable logistic regression analysis showed no
correlation between SES and staging procedures and preoperative TNM stage. The
adjusted odds ratio (OR) for stent placement was 0.82 (95% CI 0.71-0.95),
indicating that with an increase in SES by 1200 [euro], the likelihood that a
stent was placed declined by 18%. Patients with a higher SES more frequently
underwent resection or were treated with chemotherapy (OR: 1.15; 95% CI 1.01-1.32
and OR: 1.16; 95% CI 1.02-1.32, respectively). Socio-economic factors are
involved in oesophageal cancer in The Netherlands, as patients with a higher SES
are more likely to have an adenocarcinoma and patients with a lower SES a
squamous cell carcinoma. Moreover, the correlations between SES and different
treatment modalities suggest that both patient and doctor determinants contribute
to the decision on the most optimal treatment modality in patients with
oesophageal cancer.
PMID- 17031407
TI - Cost-effectiveness of oxaliplatin and capecitabine in the adjuvant treatment of
stage III colon cancer.
AB - For many years, the standard treatment for stage III colon cancer has been
surgical resection followed by 5-fluorouracil in combination with folinic acid (5
FU/LV). Ongoing clinical trial evidence suggests that capecitabine and
oxaliplatin (in combination with 5-FU/LV) may improve disease-free survival and
overall survival when compared against 5-FU/LV alone in the adjuvant setting.
This study evaluates the cost-effectiveness profiles of these two regimens in
comparison to standard chemotherapy, using evidence from two international
randomised controlled trials. Survival modelling techniques were employed to
extrapolate survival curves from the two trials in order to estimate the long
term benefits of alternative treatment options over the remaining lifetime of
patients. The health economic analysis suggests that capecitabine is expected to
produce greater health gains at a lower cost than 5-FU/LV. Oxaliplatin in
combination with 5-FU/LV is estimated to cost pounds 2970 per additional QALY
gained when compared to 5-FU/LV alone. Future research should attempt to
elucidate uncertainties concerning the optimal roles of capecitabine and/or
oxaliplatin in the adjuvant setting in order to achieve the maximum level of
clinical benefit.
PMID- 17031408
TI - Vinflunine: a new active drug for second-line treatment of advanced breast
cancer. Results of a phase II and pharmacokinetic study in patients progressing
after first-line anthracycline/taxane-based chemotherapy.
AB - To evaluate the single agent activity, pharmacokinetics and tolerability of the
novel tubulin targeted agent vinflunine (VFL) (320 mg m(-2) q 21 days) as second
line chemotherapy in patients with metastatic breast carcinoma (MBC). All
patients had disease progression after anthracycline/taxane (A/T) therapy. They
could have received a nonanthracycline adjuvant treatment and subsequently
received a first-line A/T combination for advanced/metastatic disease; or
relapsed >6 months after completion of adjuvant A/T therapy and were subsequently
treated with the alternative agent; or relapsed within 6 months from an adjuvant
A/T combination. Objective response was documented in 18 of 60 patients enrolled
(RR: 30% (95% confidence interval (CI): 18.9-43.2%)). Among the responders, seven
patients had relapsed during a period of <3 months from taxane-based regimen
yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI:
4.2-7.2), median progression-free survival was 3.7 months (95% CI: 2.8-4.2) and
median overall survival was 14.3 months (95% CI: 9.2-19.6). The most frequent
adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of
patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of
patients) and constipation (grade 3 in 11.7% of patients) were also common; these
were non-cumulative and manageable permitting achievement of a good relative dose
intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in
the management of MBC patients previously treated with (A/T)-based regimens.
These encouraging phase II results warrant further investigation of this novel
agent in combination with other active agents in this setting or in earlier
stages of disease.
PMID- 17031410
TI - Remote monitoring of implantable cardioverter defibrillator.
PMID- 17031409
TI - Mathematical models of targeted cancer therapy.
AB - Improved understanding of the molecular underpinnings of cancer initiation and
progression has led to the development of targeted cancer therapies. The
importance of these new methods of cancer treatment necessitates further research
into the dynamic interactions between cancer cells and therapeutic agents, as
well as a means of analysing their relationship quantitatively. The present
review outlines the application of mathematical modelling to the dynamics of
targeted cancer therapy, focusing particular attention on chronic myeloid
leukaemia and its treatment with imatinib (Glivec).
PMID- 17031411
TI - Interference between cellular telephones and implantable rhythm devices: a review
on recent papers.
AB - BACKGROUND: Cardiac pacemakers and implantable defibrillators are potentially
susceptible to electromagnetic interferences as they have complex circuitry for
sensing and communication purposes. Cellular telephones being an important source
of electromagnetic waves are likely to cause interference in the function of
these devices. METHODS: A systematic analysis of studies on interaction between
cellular telephones and implantable devices was done using professional databases
for literature. Related articles and references of relevant articles were also
searched for suitable studies. RESULTS: Fourteen studies on pacemakers and eight
studies on implantable defibrillators were identified. No dangerous malfunction
was found in any of the analyzed studies, but most of the studies noted
interference with device function when the phone was operated very close to the
device. Interference was minimally in those devices with built in feed-through
filters for eliminating electromagnetic interference. Device programming and
interrogation were the most susceptible phases of operation. SUMMARY: Cellular
phones are likely to interfere with implantable rhythm devices if operated in
close proximity or during programming of the device. Patients with implanted
devices can safely use cellular phones if they are not carried close to the
implanted devices or operated near them. Carrying the cellular phones in the belt
position, receiving calls in the ear opposite to the side of the implanted device
and keeping the phone as far away as possible while dialing can be considered a
safe practice. Interrogation of the devices should take place exclusively in
areas where utilization of cellular phones is strictly prohibited. Studies on
pacemakers published in the current decade have shown much lesser rates of
interference, possibly due to improvement in device technology.
PMID- 17031412
TI - Shortening of ventriculoatrial interval after ablation of an accessory pathway.
PMID- 17031413
TI - Narrow complex tachycardia with alternating R-R intervals. What is the mechanism?
PMID- 17031414
TI - Stable atrial sensing on long-term follow up of VDD pacemakers.
AB - BACKGROUND: The hemodynamic advantages of maintaining AV synchrony through AV
synchronous pacing are widely known as compared to single chamber pacing. DDD
pacemaker implantation entails higher cost and is technically more challenging
than the VDD pacemaker. METHODS: Seventy one patients underwent VDD lead
(Biotronik GmbH, St. Jude Medical and Medtronic Inc.) implantation at KEM
hospital, Mumbai during a period of 3 years through subclavian, axillary and
cephalic routes for degenerative, post-surgical or congenital high grade
atrioventricular or complete heart block. They were followed up regularly for
ventricular threshold and P wave amplitude of the floating atrial dipole.
RESULTS: Follow up data of almost 95% of patients is available for a period of
15.8 +/- 6.7 months. P wave amplitude at implant was 2.1 +/- 0.7mV and at follow
up 1.1 +/- 0.6mV with mean ventricular threshold of <0.5V at implant and <1V at
follow-up. CONCLUSION: Implantation of a single lead VDD pacemaker is possible in
all patients with symptomatic AV block and intact sinus node function without any
technical complications. P wave sensing is reliable and consistent with floating
atrial lead at an average follow up of 15.8 months, providing an excellent
alternative to DDD pacemaker implantation.
PMID- 17031415
TI - Early outcomes of out-of-hospital cardiac arrest after early defibrillation: a 24
months retrospective analysis.
AB - INTRODUCTION: Cardiovascular disease remains the most common cause of death in
the United States and most other Western nations. Among these deaths, sudden, out
of-hospital cardiac arrest claims approximately 1000 lives each day in the United
States alone. Most of these cardiac arrests are due to ventricular fibrillation.
Though highly reversible with the rapid application of a defibrillator,
ventricular fibrillation is otherwise fatal within minutes, even when
cardiopulmonary resuscitation is provided immediately. The overall survival rate
in the United States is estimated to be less than 5 percent. Recent developments
in automated-external-defibrillator technology have provided a means of
increasing the rate of prompt defibrillation after out-of-hospital cardiac
arrest. After minimal training, nonmedical personnel (e.g., flight attendants and
casino workers) are also able to use defibrillators in the workplace, with
lifesaving effects. Nonetheless, such programs have involved designated personnel
whose job description includes assisting persons who have had sudden cardiac
arrest. Data are still lacking on the success of programs in which automated
external defibrillators have been installed in public places to be used by
persons who have no specific training or duty to act. MATERIALS AND METHODS: All
patients who had an out-of-hospital cardiac arrest between January 2003 and
December 2004 and who received early defibrillation for ventricular fibrillation
were included. We conducted a 24 months retrospective population-based analysis
of the outcome in our population. RESULTS: Over a 24 month period, 446 people had
non-traumatic cardiac arrest, and in all of them it was observed to be
ventricular fibrillation. In a very few cases, the defibrillator operators were
good Samaritans, acting voluntarily. Eighty-nine patients (about 19%) with
ventricular fibrillation were successfully resuscitated, including eighteen who
regained consciousness before hospital admission. CONCLUSION: Automated external
defibrillators deployed in readily accessible, well-marked areas, are really very
effective in assisting patients with cardiac arrest. However, it's quite true
that, in the cases of survivors, most of our users had good prior training in the
use of these devices.
PMID- 17031416
TI - Current developments in microvolt T-wave alternans.
AB - Microvolt T-wave alternans (MTWA), the beat-to-beat fluctuation in T wave
amplitude and morphology, is closely linked to vulnerability to ventricular
arrhythmias in various experimental and clinical conditions. Clinically, MTWA is
most commonly measured using the spectral method, although non-spectral methods
for its assessment from ambulatory electrocardiographical recordings also have
been developed. Recent studies suggest that the quantitative assessment of TWA
may also be clinically relevant. The standardisation of the criteria for abnormal
MTWA test still needs to be completed. The expansion of indications for
implantable cardioverter-defibrillator (ICD) therapy following the positive
results of the MADIT-II and SCD-HeFT trials might have unacceptable economic and
medical consequences, and therefore new tests are needed to better discriminate
patients who will and will not benefit from ICD implantation. A recent meta
analysis of MTWA studies revealed an overall positive predictive value for
arrhythmic events of 19.3%, negative predictive value of 97.2%, and 3.77%
univariate relative risk of arrhythmic events. The negative predictive value of
MTWA in MADIT-II type patients has been reported to be 97.5%. The predictive
value of the test varied significantly in different patient population. Current
data support the use of MTWA testing for evaluation of patients with low ejection
fraction who are considered for ICD implantation. The independence of the
prognostic value of MTWA from other clinical and electrophysiological variables
needs further confirmation.
PMID- 17031417
TI - Minimally invasive mapping guided surgical treatment of atrial fibrillation.
Utopia or near future?
AB - Isolation of the pulmonary veins has been used as surgical treatment for atrial
fibrillation (AF) from the early 90s, as it was incorporated in the Maze
procedure. With the evidence that triggers form this area can induce AF, the Maze
III procedure has been adapted and modified towards a single lesion around the
pulmonary veins for the treatment of paroxysmal and chronic AF in some centers.
New ablation techniques with a diversity of energy sources further paved the way
for less invasive procedures. Minimal invasive techniques to prevent major
surgery may potentially make the treatment available for a patient population
that do not have to undergo cardiac surgery for other reasons. Besides these
technical developments, high density mapping can be used to identify the AF
substrate in the individual patient and optimization of the treatment by local
substrate guided ablation. This review aims to summarize the robotic and
thoracoscopic techniques to isolate the pulmonary veins. Furthermore, it is
discussed why pulmonary veins isolation may be effective in patients with chronic
AF, and whether there is a role for mapping guided minimal invasive surgical
treatment of AF in the near future.
PMID- 17031418
TI - Korean American Men's Perceptions about Smoking-Related Symptomatology:
Implications for Intervention.
AB - This study examines what midlife and older (age 45 to 74) Korean American men who
are current or former cigarette smokers think cause symptoms or health problems
that may be related to smoking cigarettes. The study also examines how those
perceptions influence attitudes and behaviors regarding smoking cessation.
Separate focus groups were conducted with seven current smokers and nine former
smokers in the Korean language in a Korean American. Current smokers experienced
few symptoms or health problems that they attribute to smoking, and they
generally do not regard smoking as a cause of symptoms or health problems. Former
smokers generally quit smoking in response to experiencing a wide range of
symptoms or health problems that they attribute to smoking or that they believe
smoking exacerbates. A pervasive theme among both groups is that health is a
function of a person's physical constitution. The perception is that those born
with a strong or special physical constitution are able to smoke and be healthy;
persons with a weak physical constitution or who are predisposed to be ill should
not smoke or should quit smoking. Smoking-cessation interventions for midlife and
older Korean American men should take these findings into account.
PMID- 17031419
TI - Gastric Cancer in Korean Americans: Risks and Reductions.
AB - Gastric cancer is one of the leadings cause of cancer worldwide. However, Koreans
have the highest reported incidence of this deadly disease. Risk factors
predisposing to the formation of gastric cancer include a combination of
environmental risks, such as diet and infection (Helicobacter pylori), and, in
some cases, genetic predisposition. Early screening and detection is essential to
reduce gastric cancer mortality. The low prevalence and late onset of gastric
cancer in Americans, compared to Korean Americans, however, has hindered our
ability to risk stratify, screen, and improve early detection in Korean
Americans, thereby contributing to the increasing mortality in this group.
Gastric cancer control must focus on improved medical technology, in combination
with community outreach, education, and awareness. Korean community services,
church-based groups, media campaigns, medical communities, both academic and
community based, and industry collaborations are essential to heighten awareness
about gastric cancer in Korean Americans. Efforts to reduce the burden of gastric
cancer in Korean Americans must focus on the dissemination of information to
those most affected by the disease and those serving this community.
PMID- 17031420
TI - Cultural Perspectives on Korean American Cancer Control.
AB - This paper emphasizes the importance of sociocultural research for successful
ethnic-based cancer control. The article first delineates some demographic
characteristics of Korean Americans and then describes six subcultural groups
within this population, illuminating that Korean Americans are a diverse people.
The author emphasizes that any cancer control program needs to acknowledge these
cultural differences in selecting the target population, identifying intervention
strategies, and training a team of health-care professionals, as well as in
determining psychological factors related to cancer. The author also suggests
that the traditional Korean American notion of health, the preventive approach to
illness by using food as medicine, the traditional classification of body types,
and the sasang theory for the treatment of illness are all important factors
worthy of further research. Finally, the synchronistic and holistic approach to
health common among Korean Americans is described by citing recent studies of
cancer control that combine the use of Western medicine together with proper
physical exercise, diet control, and psychological and family counseling.
PMID- 17031421
TI - Magnetic assisted navigation in electrophysiology and cardiac resynchronisation:
a review.
AB - Magnetic assisted navigation is a new innovation that may prove useful in
catheter ablation of cardiac arrhythmias and cardiac resynchronization therapy.
The ability to steer extremely floppy catheters and guidewires may allow for
these to be positioned safely in previously inaccessible areas of the heart. The
integration of other new technology, such as image integration and
electroanatomic mapping systems, should advance our abilities further. Although
studies have shown the technology to be feasible, with the advantage to the
physician of decreased radiation exposure, studies need to be performed to show
additional benefit over standard techniques.
PMID- 17031422
TI - Synthesis, surface functionalization, and properties of freestanding silicon
nanocrystals.
AB - Freestanding silicon nanoparticles (FS-nc-Si) have intriguing chemical and
optical properties. The present contribution outlines known synthetic
methodologies and protocols for surface functionalization. Recent advancements in
tailoring the photoluminescence properties of FS-nc-Si and future research
directions will be briefly discussed.
PMID- 17031423
TI - Crystal engineering of coordination polymers using 4,4'-bipyridine as a bond
between transition metal atoms.
AB - Coordination polymers have attracted an enormous interest among chemists due to
their novel physical and chemical properties. This review describes the role of
4,4'-bipyridine in discovering various coordination polymers with novel
topologies that range from one-dimensional to three dimensional. The geometries
of coordination polymers of bipy include linear, zigzag, four-fold helices,
molecular antenna, ladder, railroad, double, triple and quadruple chains,
bilayer, square and rectangular grid, honeycomb layers, Lincoln Logs, 3D frames,
diamondoid, 4(2) x 8(2) and cubic networks.
PMID- 17031424
TI - Supported cobalt mediated radical polymerization (SCMRP) of vinyl acetate and
recycling of the cobalt complex.
AB - Cobalt complexes supported on silica and Merrifield resin are effective mediators
for the controlled radical polymerization of vinyl acetate.
PMID- 17031425
TI - Gold nanocomposites with rigid fully conjugated heteroditopic ligands shell as
nanobuilding blocks for coordination chemistry.
AB - Monodisperse and solvent adaptable gold nanoparticles stabilized by rigid and
fully conjugated modified neocuproinium and terpyridinium salts have been
characterized and further used as nanobuilding blocks for the synthesis of gold
nanoparticles functionalized by polypyridyl ruthenium complexes.
PMID- 17031426
TI - Synthesis of the DEF-bis-spiroacetal of spirastrellolide A exploiting a double
asymmetric dihydroxylation/spiroacetalisation strategy.
AB - An efficient synthesis of the C(26)-C(40) tricyclic [5,6,6]-bis-spiroacetal
segment of the marine macrolide spirastrellolide A has been developed, exploiting
a novel double Sharpless asymmetric dihydroxylation/spiroacetalisation sequence.
PMID- 17031427
TI - The reductive amination of aldehydes and ketones by catalytic use of
dibutylchlorotin hydride complex.
AB - The reductive amination of aldehydes or ketones using Ph(2)SiH(2) or PhSiH(3) has
been effectively promoted by the direct use of Bu(2)SnClH-pyridine N-oxide as a
catalyst; this method has advantages in terms of its mild conditions and wide
application to various carbonyls and amines, including aliphatic examples.
PMID- 17031428
TI - New palladium catalysed reactions of bromoporphyrins: synthesis and crystal
structures of nickel(ii) complexes of primary 5-aminoporphyrin, 5,5'
bis(porphyrinyl) secondary amine, and 5-hydroxyporphyrin.
AB - Primary aminoporphyrin, secondary bis(porphyrinyl)amine and hydroxyporphyrin
complexes have been isolated and characterised both spectroscopically and
crystallographically from the reaction of 5-bromo-10,15,20
triphenylporphyrinatonickel(ii) with hydrazine under palladium catalysis.
PMID- 17031429
TI - The photoinduced long-lived charge-separated state of Ru(bpy)3-methylviologen
with cucurbit[8]uril in aqueous solution.
AB - A stable 1 : 1 inclusion complex of Ru(bpy)(3)-MV(2+) with cucurbit[8]uril
(CB[8]) is formed in aqueous solution; upon light irradiation, a long lived (tau
approximately 2 micros) charge-separated state Ru(3+)-MV(+ )-CB[8] is observed.
PMID- 17031430
TI - Facile in situ preparation of biologically active multivalent glyconanoparticles.
AB - Biologically active multivalent glyconanoparticles are prepared in an extremely
simple method by reduction of well-defined glycopolymers, prepared by RAFT
polymerisation, in an aqueous solution of HAuCl(4).
PMID- 17031431
TI - A high-throughput screening assay for hydroxynitrile lyase activity.
AB - A high-throughput screening assay for hydroxynitrile lyase activity accepting a
wide range of HNL-substrates is presented, which is useful either for enzyme
fingerprinting or screening of huge variant libraries generated in metagenome or
directed evolution approaches.
PMID- 17031432
TI - The isolable matryoshka nesting doll icosahedral cluster [As@Ni12@As20]3- as a
"superatom": analogy with the jellium cluster Al13- generated in the gas phase by
laser vaporization.
AB - The valence electrons in the recently reported icosahedral cluster
[As@Ni(12)@As(20)](3-) with a Russian matryoshka nesting doll structure can be
partitioned so that the central As atom has the rare gas configuration, as As(3
), and the intermediate Ni(12) icosahedron receives 40 electrons from the lone
pairs of the outer As(20) dodecahedron to be isoelectronic with the Al(13)(-)
jellium cluster found in molecular beam experiments.
PMID- 17031433
TI - Dynamic ligation at the first amine-coordinated iron hydrogenase active site
mimic.
AB - The first model of the iron hydrogenase active site has been prepared in which an
amine ligand is loosely coordinated to an Fe(i) centre, and can be replaced by a
solvent molecule; irrespective of the ligand set, the one electron reduction of
both complexes is chemically reversible and is shown to proceed through the same
species which features a bridging CO ligand.
PMID- 17031434
TI - Total synthesis of antillatoxin.
AB - The total synthesis of natural (4R,5R)-antillatoxin and its analog (4S,5S)
antillatoxin has been achieved; the optically pure key intermediates were
prepared from indium mediated allylation of either primary or secondary allylic
bromide with aldehyde in aquoues media, followed by highly selective Luche's
reduction and chiral resolution.
PMID- 17031435
TI - Competitive photoinduced electron transfer by the complex formation of porphyrin
with cyclodextrin bearing viologen.
AB - Photoinduced electron transfer between a porphyrin and a new guest cyclodextrin
bearing viologen occurs by a supramolecular formation with conformational change
of a guest molecule.
PMID- 17031436
TI - Solution structures of thiopeptide antibiotics.
AB - A detailed NMR study of the thiopeptide amythiamicin D establishes its solution
conformation and the presence of a single intramolecular hydrogen bond involving
NH13 and O28, and also provides the first evidence for self-association of
thiopeptides in solution.
PMID- 17031437
TI - Solution state coordination polymers featuring wormlike macroscopic structures
and cage-polymer interconversions.
AB - In the absence of coordinating solvents and anions, silver salts and
triphosphines form viscous, thixotropic coordination polymers in solution, which
aggregate into unusual wormlike macroscopic structures and undergo cage-polymer
interconversions depending on the stoichiometry and presence of templating
anions.
PMID- 17031438
TI - Self-aggregated perfluoroalkylated hexa-peri-hexabenzocoronene fibers observed by
cryo-SEM and fluorescence spectroscopy.
AB - The self-assembled architectures in solution of a new HBC derivative bearing
perfluoroalkylated side chains were investigated by optical excitation and
emission spectroscopy and correlated to cryo-SEM, a new technique in organic
chemistry.
PMID- 17031439
TI - Selective detection of cesium by a water-soluble fluorescent molecular sensor
based on a calix[4]arene-bis(crown-6-ether).
AB - A tetrasulfonated calixarene with two appended crowns, each including a
dioxycoumarin fluorophore, is highly soluble in water and shows excellent
selectivity for cesium ions.
PMID- 17031440
TI - Novel immobilization method of enzymes using a hydrophilic polymer support.
AB - A novel immobilization of an enzyme with a hydrophilic polymer support in organic
solvents has been developed utilizing the "polymer-incarcerated (PI) method",
which has been used to immobilize metal catalysts; the kinetic resolution of
secondary alcohols was found to proceed more smoothly using immobilized lipases
(CALB) than free lipases.
PMID- 17031441
TI - A short water-soluble self-assembling peptide forms amyloid-like fibrils.
AB - A water-soluble tripeptide Val-Ile-Ala (VIA) , bearing sequence identity with the
C-terminal portion of the Alzheimer Abeta-peptide (Abeta(40-42)), self-assembles,
in crystalline form, to produce an intermolecularly hydrogen bonded
supramolecular beta-sheet structure which self-associates to form straight,
unbranched nanofibrils exhibiting amyloid-like behavior; in contrast, the
synthetic tripeptide Ala-Val-Ile (AVI) self-assembles to produce a beta-sheet
structure that forms branched nanofibrils which do not show any characteristic
features of amyloid-like fibrils.
PMID- 17031442
TI - Gas-phase regiocontrolled generation of charged amino acid and peptide radicals.
AB - The combined use of advanced mass spectrometry experiments, condensed-phase
synthesis of serine and homoserine nitrate ester radical precursors, and high
level ab initio calculations provides a powerful way of examining the fundamental
reactivity of radicals derived from peptides.
PMID- 17031443
TI - Efficient visible light-active N-doped TiO2 photocatalysts by a reproducible and
controllable synthetic route.
AB - A reproducible and controllable method allows the synthesis of practical
quantities of efficient, visible light active TiO(2)(N) photocatalysts in which
the nitrogen content may be varied to achieve optimum performance.
PMID- 17031444
TI - Annulation of beta-aryl-alpha-nitro-alpha,beta-enals and 2,2-dimethyl-1,3-dioxan
5-one: a one-step assembly of nitrocyclitols. Application to a short practical
synthesis of (+/-)-7-deoxy-2-epi-pancratistatin tetraacetate.
AB - A novel, highly stereocontrolled formal [3 + 3] annulation of beta-aryl-alpha
nitro-alpha,beta-enals with the enamine derived from 2,2-dimethyl-1,3-dioxan-5
one and pyrrolidine afforded protected nitrocyclitols with five newly created
stereocentres and constituted the key step in a short, gram-scale synthesis of a
pancratistatin analogue.
PMID- 17031445
TI - An enantioselective fluorescence sensing assay for quantitative analysis of
chiral carboxylic acids and amino acid derivatives.
AB - A chiral 1,8-diacridylnaphthalene-derived fluorosensor exhibiting a C(2)
symmetric cleft designed for stereoselective interactions with hydrogen bond
donors has been used for the determination of both concentration and enantiomeric
composition of carboxylic acids and amino acid derivatives.
PMID- 17031446
TI - Highly-oxidised, sulfur-rich, mixed-valence vanadium(IV/V) complexes.
AB - The reactions of [V(2)(micro-S(2))(2)(S(2)CNR(2))(4)] (R = alkyl) with NOBF(4)
produce highly-oxidised, sulfur-rich, V(iv/v) complexes, [V(2)(micro
S(2))(2)(S(2)CNR(2))(4)]BF(4), that exhibit 15-line EPR spectra and structures
consistent with Class III mixed-valence behaviour.
PMID- 17031447
TI - High rates of psychiatric co-morbidity in PDD-NOS.
AB - Rates of co-morbid psychiatric conditions in children with Pervasive
Developmental Disorder-Not Otherwise Specified (PDD-NOS) are hardly available,
although these conditions are often considered as more responsive to treatment
than the core symptoms of PDD-NOS. Ninety-four children with PDD-NOS, aged 6-12
years were included. The DISC-IV-P was administered. At least one co-morbid
psychiatric disorder was present in 80.9% of the children; 61.7% had a co-morbid
disruptive behavior disorder, and 55.3% fulfilled criteria of an anxiety
disorder. Compared to those without co-morbid psychiatric disorders, children
with a co-morbid disorder had more deficits in social communication. Co-morbid
disorders occur very frequently in children with PDD-NOS, and therefore clinical
assessment in those children should include assessment of co-morbid DSM-IV
disorders.
PMID- 17031448
TI - Memory illusion in high-functioning autism and Asperger's disorder.
AB - In this study, 13 individuals with high-functioning autism (HFA), 15 individuals
with Asperger's disorder (AD), and age-, and IQ-matched controls were presented a
list of sentences auditorily. Participants then evaluated semantically related
but new sentences and reported whether they were old or new. The total rates of
false recognition for semantically related sentences were similar among the three
groups. Nevertheless, memory illusion on some aspects was reduced in HFA
participants. These results suggest that HFA have difficulties in semantic
association. Although individuals with AD showed no quantitative abnormalities of
memory illusion, some contributing factors were atypical. These findings are
discussed in terms of schema theory, enhanced perceptual processing hypothesis,
and weak central coherence hypothesis.
PMID- 17031449
TI - Autism spectrum phenotype in males and females with fragile X full mutation and
premutation.
AB - The behavioural phenotype of autism was assessed in individuals with full
mutation and premutation fragile X syndrome (FXS) using the Autism Diagnostic
Observation Scale-Generic (ADOS-G) and the Autism Diagnostic Interview (ADI-R).
The participants, aged 5-80 years, comprised 33 males and 31 females with full
mutation, 7 males and 43 females with premutation, and 38 non-fragile X relatives
(29 males, 9 females). In the full mutation group, a total of 67% males and 23%
females met either the Autism Disorder (AD) or the Autism Spectrum Disorder (ASD)
criteria on at least one of the diagnostic tests. In the premutation group, 14%
males and 5% females met the ADOS-G criteria for ASD. The presence of autism
manifestations in males and females with full mutation and premutation provide
support for a spectrum view.
PMID- 17031450
TI - Assessing the early characteristics of autistic disorder using video analysis.
AB - The behaviours of infants were observed using home videos, in an attempt to
identify social difficulties characteristic of infants with autistic disorder.
Three groups of infants were analysed: 15 infants who had later been diagnosed
with autism, 15 infants who had a developmental or language delay, and 15
typically developing infants. Social behaviours were coded using both
quantitative and qualitative measures. The principal discriminating items between
the groups were found to be 'peer interest', 'gaze aversion', 'anticipatory
postures', and 'proto-declarative showing'. The results suggest that these
children later diagnosed with autism are clinically distinct from their peers
before the age of two years, and that there are clearly observable behaviours
which are important predictors of autistic disorder in pre-verbal children.
PMID- 17031451
TI - Accuracy of dual-source CT coronary angiography: First experience in a high pre
test probability population without heart rate control.
AB - The aim of this study was to assess the diagnostic accuracy of dual-source
computed tomography (DSCT) for evaluation of coronary artery disease (CAD) in a
population with extensive coronary calcifications without heart rate control.
Thirty patients (24 male, 6 female, mean age 63.1+/-11.3 years) with a high pre
test probability of CAD underwent DSCT coronary angiography and invasive coronary
angiography (ICA) within 14+/-9 days. No beta-blockers were administered prior to
the scan. Two readers independently assessed image quality of all coronary
segments with a diameter > or =1.5 mm using a four-point score (1: excellent to
4: not assessable) and qualitatively assessed significant stenoses as narrowing
of the luminal diameter >50%. Causes of false-positive (FP) and false-negative
(FN) ratings were assigned to calcifications or motion artifacts. ICA was
considered the standard of reference. Mean body mass index was 28.3+/-3.9 kg/m2
(range 22.4-36.3 kg/m2), mean heart rate during CT was 70.3+/-14.2 bpm (range 47
102 bpm), and mean Agatston score was 821+/-904 (range 0-3,110). Image quality
was diagnostic (scores 1-3) in 98.6% (414/420) of segments (mean image quality
score 1.68+/-0.75); six segments in three patients were considered not assessable
(1.4%). DSCT correctly identified 54 of 56 significant coronary stenoses. Severe
calcifications accounted for false ratings in nine segments (eight FP/one FN) and
motion artifacts in two segments (one FP/one FN). Overall sensitivity,
specificity, positive and negative predictive value for evaluating CAD were 96.4,
97.5, 85.7, and 99.4%, respectively. First experience indicates that DSCT
coronary angiography provides high diagnostic accuracy for assessment of CAD in a
high pre-test probability population with extensive coronary calcifications and
without heart rate control.
PMID- 17031452
TI - Teleradiology applications with DICOM-e-mail.
AB - For the connection of several partners to a Dicom-e-mail based teleradiology
network concepts were developed to allow the integration of different
teleradiology applications. The organisational and technical needs for such an
integration were analysed. More than 60 institutions including 23 hospitals in
the Rhein-Neckar-Region, Germany were connected. The needed functionality was
grouped in six teleradiology applications (emergency consultation, tele-guided
examinations, expert consultations, cooperative work, scientific cooperations and
homework with on call services) and their technical and organisational needs
according to availability, speed of transfer, workflow definitions and data
security needs was analysed. For the local integration of teleradiology services
the setup and workflow is presented for a standalone teleradiology workstation
and a server based teleradiology gateway. The line type needed for different
groups of applications and users is defined. The security concept and fallback
strategies are laid out, potential security problems and sources of errors are
discussed. The specialties for the emergency teleradiology application are
presented. The DICOM-e-mail protocol is a flexible and powerful protocol that can
be used for a variety of teleradiology applications. It can meet the conditions
for emergency applications but is limited if synchronous applications like
teleconferences are needed.
PMID- 17031453
TI - Cost effectiveness of coronary angiography and calcium scoring using CT and
stress MRI for diagnosis of coronary artery disease.
AB - We compared the cost effectiveness of recent approaches [coronary angiography and
calcium scoring using computed tomography (CT) and stress magnetic resonance
imaging (MRI)] to the diagnosis of coronary artery disease (CAD) with those of
the traditional diagnostic modalities [conventional angiography (CATH), exercise
ECG, and stress echocardiography] using a decision tree model. For patients with
a 10% to 50% pretest likelihood of coronary artery disease, non-invasive coronary
angiography using CT was the most cost effective approach, with costs per
correctly identified CAD patient of euro4,435 (10% likelihood) to euro1,469 (50%
likelihood). Only for a pretest likelihood of 30% to 40% was calcium scoring
using CT more cost effective than any of the traditional diagnostic modalities,
while MRI was not cost effective for any pretest likelihood. At a pretest
likelihood of 60%, CT coronary angiography and CATH were equally effective, while
CATH was most cost effective for a pretest likelihood of at least 70%. In
conclusion, up to a pretest likelihood for coronary artery disease of 50%, CT
coronary angiography is the most cost-effective procedure, being superior to the
other new modalities and the most commonly used traditional diagnostic
modalities. With a very high likelihood for disease (above 60%), CATH is the most
effective procedure from the perspective of society.
PMID- 17031454
TI - MR-compatible assistance system for punction in a high-field system: device and
feasibility of transgluteal biopsies of the prostate gland.
AB - We present the first cadavic study results concerning the feasibility of the use
of an MR-guided assistance system, Innomotion (Innomedic, Herxheim, Germany), for
accurate and consistent placement of percutaneous needles in the prostate gland.
The MR-compatible assistance system consists of a C-arch, guiding arm and
application module (AMO). T1-weighted fast low angle shot (FLASH) 2-D-GRE
sequence (TR/TE=110/4 ms) and T2-weighted turbo spin-echo (TSE)-sequences
(TR/TE=3200/97 ms) in transversal orientation were used for the monitoring of the
punction of the prostate gland. Planning and control of the intervention is to be
made outside the scanner room on a desktop computer that receives DICOM images
from the scanner. Servopneumatic drives move the AMO to the insertion point. The
physician has to introduce the punction needle manually. The mean deviation of
the needle tip to the target in a gel phantom was 0.35 mm. An accurate punction
of the prostate gland can easily be performed using this system with a
transgluteal access. The T2-weighted images are superior for the evaluation of
the prostate anatomy and the needle position during the interventions. In
conclusion, our preliminary results indicate that this MR-guided assistance
system is suitable for an accurate transgluteal needle placement in the prostate.
PMID- 17031455
TI - [Laparoscopy for abdominal trauma].
AB - With increasing experience in minimally invasive surgery, laparoscopy's role in
abdominal trauma can be defined exactly. Main exclusion criteria are hemodynamic
instability and increased intracranial pressure. A literature review of 1996 to
2006 reveals perforating injury mainly of the left thoracoadominal area as the
most important indication for laparoscopy . Its goal is to determine
intraperitoneal lesions and integrity of the abdominal wall and diaphragm. Minor
injuries of the parenchymatous organs and diaphragm can be successfully repaired
laparoscopically. In blunt abdominal trauma, laparoscopy is used as a
complementary diagnostic device in case ultrasound and multislice CT show unclear
findings and the patient's clinical status requires invasive measures. The clear
weakness of laparoscopy in abdominal trauma is its inability to identify reliably
hollow viscus perforation and retroperitoneal injury. In this, sensitivity is
only 25%. In case of proven lesions of the gastrointestinal tract, conversion to
laparotomy is to be considered. Despite the reports on laparoscopic treatment,
open repair of hollow organ injuries is still to be recommended.
PMID- 17031456
TI - Dynamic model of the process of protein synthesis in eukaryotic cells.
AB - Protein synthesis is the final step of gene expression in all cells. In order to
understand the regulation of this process, it is important to have an accurate
model that incorporates the regulatory steps. The model presented in this paper
is composed of set of differential equations which describe the dynamics of the
initiation process and its control, as well as peptide elongation, starting with
the amino acids available for peptide creation. A novel approach for modeling the
elongation process permits useful prediction of protein production and
consumption of energy and amino acids, as well as ribosome loading rate and
ribosome spacing on the mRNA.
PMID- 17031457
TI - Evidence for an early gene duplication event in the evolution of the
mitochondrial transcription factor B family and maintenance of rRNA
methyltransferase activity in human mtTFB1 and mtTFB2.
AB - Most metazoans have two nuclear genes encoding orthologues of the well
characterized Saccharomyces cerevisiae mitochondrial transcription factor B (sc
mtTFB). This class of transcription factors is homologous to the bacterial KsgA
family of rRNA methyltransferases, which in Escherichia coli dimethylates
adjacent adenine residues in a stem-loop of the 16S rRNA. This
posttranscriptional modification is conserved in most metazoan cytoplasmic and
mitochondrial rRNAs. Homo sapiens mitochondrial transcription factor B1 (h
mtTFB1) possesses this enzymatic activity, implicating it as a dual-function
protein involved in mitochondrial transcription and translation. Here we
demonstrate that h-mtTFB2 also has rRNA methyltransferase activity but is a less
efficient enzyme than h-mtTFB1. In contrast, sc-mtTFB has no detectable rRNA
methyltransferase activity, correlating with the lack of the corresponding
modification in the mitochondrial rRNA of budding yeast. Based on these results,
and reports that Drosophila melanogaster mtTFB1 and mtTFB2 do not have completely
overlapping functions, we propose a model for human mtDNA regulation that takes
into account h-mtTFB1 and h-mtTFB2 likely having partially redundant
transcription factor and rRNA methyltransferase functions. Finally, phylogenetic
analyses of this family of proteins strongly suggest that the presence of two
mtTFB homologues in metazoans is the result of a gene duplication event that
occurred early in eukaryotic evolution prior to the divergence of fungi and
metazoans. This model suggests that, after the gene duplication event,
differential selective pressures on the rRNA methyltransferase and transcription
factor activities of mtTFB genes occurred, with extreme cases culminating in the
loss of one of the paralogous genes in certain species.
PMID- 17031459
TI - Nonrandom representation of sex-biased genes on chicken Z chromosome.
AB - Several lines of evidence suggest that the X chromosome of various animal species
has an unusual complement of genes with sex-biased or sex-specific expression.
However, the study of the X chromosome gene content in different organisms
provided conflicting results. The most striking contrast concerns the male-biased
genes, which were reported to be almost depleted from the X chromosome in
Drosophila but overrepresented on the X chromosome in mammals. To elucidate the
reason for these discrepancies, we analysed the gene content of the Z chromosome
in chicken. Our analysis of the publicly available expressed sequence tags (EST)
data and genome draft sequence revealed a significant underrepresentation of
ovary-specific genes on the chicken Z chromosome. For the brain-expressed genes,
we found a significant enrichment of male-biased genes but an indication of
underrepresentation of female-biased genes on the Z chromosome. This is the first
report on the nonrandom gene content in a homogametic sex chromosome of a species
with heterogametic female individuals. Further comparison of gene contents of the
independently evolved X and Z sex chromosomes may offer new insight into the
evolutionary processes leading to the nonrandom genomic distribution of sex
biased and sex-specific genes.
PMID- 17031458
TI - Ancient phylogenetic beginnings of immunoglobulin hypermutation.
AB - Many structures and molecules closely related to those involved in the specific
process of immunoglobulin (Ig) hypermutation existed before the appearance of
primordial Ig genes. Consequently, these structures can be found even in animals
and organisms distinct from vertebrates; likewise, homologues of hypermutation
enzymes are present in a broad range of species, from bacteria to mammals. Our
analysis, based predominantly on primary structure, demonstrates the existence of
molecules similar to Ig domains, variable Ig domains (IGv), and antigen receptors
(AR) in unicellular organisms, nonvertebrate metazoans, and nonvertebrate
Coelomata, respectively. In addition, we deal here with some important structural
properties of CDR1-like segments of the selected sponge adhesion molecule GCSAMS
exhibiting chimerical Ig domain similarities, and demonstrate the occurrence of
conserved regions corresponding to Ohno's modern intact primordial building block
in the C-terminal part of IGv-related segments of nonvertebrate origin. The
results of our analysis are also discussed with respect to the possible phylogeny
of molecules preceding the hypothetical common antigen receptor ancestor.
PMID- 17031460
TI - Domain-specific positive selection contributes to the evolution of Arabidopsis
leucine-rich repeat receptor-like kinase (LRR RLK) genes.
AB - Leucine-rich repeat receptor-like kinases (LRR RLKs) comprise the largest group
within the plant receptor-like kinase (RLK) superfamily, and the Arabidopsis
genome alone contains over 200 LRR RLK genes. Although there is clear evidence
for diverse roles played by individual LRR RLK genes in Arabidopsis growth and
development, the evolutionary mechanism for this functional diversification is
currently unclear. In this study, we focused on the LRRII RLK subfamily to
investigate the molecular mechanisms that might have led to the functional
differentiation of Arabidopsis LRR RLK genes. Phylogenetic analysis of 14 genes
in this subfamily revealed three well-supported groups (I, II, and III). RT-PCR
analysis did not find many qualitative differences in expression among these 14
genes in various Arabidopsis tissues, suggesting that evolution of regulatory
sequences did not play a major role in their functional divergence. We analyzed
substitution patterns in the predicted ligand-binding regions of these genes to
examine if positive selection has acted to produce novel ligand-binding
specificities, using the nonsynonymous/synonymous rate ratio (d (N)/d (S)) as an
indicator of selective pressure. Estimates of d (N)/d (S) ratios from multiple
methods indicate that nonsynonymous substitutions accumulated during divergence
of the three lineages. Positive selection is likely to have occurred along the
lineages ancestral to groups II and III. We suggest that positive selection on
the ligand-binding sites of LRRII RLKs promoted diversification of ligand-binding
specificities and thus contributed to the functional differentiation of
Arabidopsis LRRII RLK genes during evolution.
PMID- 17031461
TI - Tandem repetitive D domains of the sperm ligand zonadhesin evolve faster in the
paralogue than in the orthologue comparison.
AB - Gene duplication is regarded as an important evolutionary mechanism creating
genetic and phenotypic novelty. At the same time, the evolutionary mechanisms
following gene duplication have been a subject of much debate. Here we analyze
the sequence evolution of zonadhesin, a mammalian sperm ligand that binds to the
oocyte zona pellucida in a species-specific manner. In pig, rabbit, and primates,
precursor zonadhesin comprises, among others, one partial and four complete
tandem repetitive D domains. The mouse precursor is distinguished by 20
additional partial D3 domains consisting of 120 amino acids each. This gene
structure allows sequence comparison in both paralogues and orthologues. Detailed
sequence analysis reveals that D domains evolve faster across paralogues than
orthologues. Moreover, at the codon level, partial D3 paralogues of mouse show
evidence of positive selection, whereas the corresponding orthologues do not.
Individual posttranslational motif patterns and positive selection point to
neofunctionalization of partial D3 paralogues of mouse, rather than
subfunctionalization. However, as we found additional evidence for homogenization
by partial gene conversion, sequence evolution of partial D3 paralogues of mouse
might be better described as a combination of divergent and convergent evolution.
So far, the divergence at the codon level has outbalanced the convergence at the
level of smaller fragments. The probable driving force behind the evolutionary
patterns observed is sexual selection. We finally discuss whether the functional
determination influences the evolutionary regime acting on sperm ligands and egg
receptors, respectively.
PMID- 17031462
TI - Experimental characterization of vibrated granular rings.
AB - We report an experimental study of the statistical properties of vibrated
granular rings. In this system, a linked rod and bead metallic chain in the form
of a ring is collisionally excited by a vertically oscillating plate. The
dynamics are driven primarily by inelastic bead-plate collisions and are
simultaneously constrained by the rings' physical connectedness. By imaging many
instances of the ring configurations, we measure the ensemble averages and
distributions of several physical characteristics on the scale of individual
beads and composite ring. We study local properties such as inter-bead separation
and inter-bonds angles, and global properties such as the radius of gyration and
center-of-mass motion. We characterize scaling with respect to the size of the
chain.
PMID- 17031463
TI - The effect of packed red blood cell storage on arachidonic acid and advanced
glycation end-product formation.
AB - INTRODUCTION: The transfusion of packed red blood cells (PRBCs) is a significant
risk to blood recipients. Blood banking procedures permit the storage of PRBCs
for up to 42 days. Storage of PRBCs can cause polymorphonuclear granulocytes
(PMNs) activation and the development of neutrophil-mediated transfusion-related
acute lung injury. The aim of our study was to determine if PRBC storage has an
influence on the formation of arachidonic acid (AA) and advanced glycation end
products (AGEs). MATERIALS AND METHODS: Twenty units of PRBCs were used to
measure AA and AGE levels. The samples were taken on the 0th, 14th, 28th, and
42nd days of PRBC storage. The AA level was analyzed by gas-liquid chromatography
mass spectrometry and AGE level by an immunoenzymatic test. RESULTS: During the
first 14 days of PRBC storage, the AA level significantly increased and then
slowly decreased. The AGE level increased continuously during the whole time of
the study. In a model experiment, the AA glycoxidation product trans-2-nonenal
(T2N) formed adducts in reaction with hemoglobin which were detectable with the
test for AGE. CONCLUSIONS: It is highly probable that the observed increase in
AGE level is related to the decrease in AA in PRBCs, which can be associated with
the formation of toxic aldehydes, especially T2N and 4-hydroxynonenal (HNE), from
AA. Glucose in the PRBCs (preservative solution) can contribute to AGE formation
as well. The formation of AGEs, HNE, and T2N in PRBCs, their influence on PMNs in
vitro, and confirmation of our assumption need further studies.
PMID- 17031464
TI - All roads lead to Rome: pathways of NKT cells promoting asthma.
AB - NKT cells are the prominent manipulator in asthma development. Asthmatic NKT
cells migrate from thymus, spleen, liver and bone marrow into blood vessels, and
then concentrate in airway bronchi mucosa. This recruitment is dependent on high
expression of CCR9 and engagement of CCL25/CCR9. NKT cells promote asthma in two
different pathways. One is an indirect pathway. NKT cells contact with CD3(+) T
cells and induce them secreting large quantity of Th2 cytokines (IL-4, IL-13),
which requires the participation of dentritic cells and the synergic signaling of
CCL25/CCR9 and CD226. The other is a direct pathway. Circulating asthmatic NKT
cells selectively highly express Th1 cytokines (IFN-gamma). Once reached airway
epithelium, most NKT cells shift to Th2-bias, highly expressing IL-4, IL-13, but
not IFN-gamma. Both pathways lead to airway hyperresponsiveness and inflammation,
asthma development. Comparing to the well documented suppressive regulatory T
cells, CD4(+)CD25(+) T cells, NKT cells perform as a novel active regulator in
asthma. These recent understanding of NKT cells performance in the development of
asthma might unveil new therapy targets and management strategies for asthma.
PMID- 17031465
TI - Increased whole blood chemiluminescence in patients with chronic renal failure
independent of hemodialysis treatment.
AB - INTRODUCTION: The luminol-enhanced whole blood chemiluminescence (LBCL) assay is
a rapid assay for the measurement of reactive oxygen species (ROS) generation by
circulating phagocytes. This study's aim was to determine if patients on
maintenance hemodialysis (HD) and non-dialyzed patients with chronic renal
failure (CRF) have altered LBCL and if dialysis itself affects ROS production in
the blood. MATERIALS AND METHODS: Twenty-six HD patients, 11 non-dialyzed
patients with CRF, and 20 gender- and age-matched healthy controls were studied.
Resting (rCl) and 2 x 10(-5) M n-formyl-methionyl-leucyl-phenylalanine-stimulated
LBCL (peak chemiluminescence: pCl, total light emission after agonist addition:
tCl) calculated per 10(4) phagocytes present in the 3-mul blood samples were
measured with a Bio-Orbit 1251 luminometer at 37 degrees C for 11 min. RESULTS:
Prior to the HD session, median rCL, pCL, and tCL were 1.5, 3.0, and 2.8 times
higher in HD patients than in healthy controls (p<0.01) and tended to increase at
the end of the session. Significant increases in tCl were observed at 30 min and
240 min (end) of HD (1023.5 vs. 1810.6 vs. 2006.8 arbitrary units x s/10(4)
phagocytes, n=9, p<0.05). Median pCl and tCl were 5.0 and 4.3 times higher in non
dialyzed patients with CRF than in healthy controls (p<0.001). However, no
significant differences were found between pre- and post-HD LBCL of HD patients
and the LBCL of non-dialyzed patients with renal failure. CONCLUSIONS: Blood from
patients with renal failure generates elevated amounts of oxidants independently
of HD treatment. This may add to the understanding of the nature of oxidative
stress and suggests the need of anti-oxidant treatment in these patients.
PMID- 17031466
TI - Langerhans cells in vulvar lichen sclerosus and vulvar squamous cell carcinoma.
AB - INTRODUCTION: Langerhans cells (LCs), specializing in antigen presentation, are a
very important part of the skin immune system (SIS). MATERIALS AND METHODS: Skin
biopsies from 22 women with vulvar lichen sclerosus (LS): 15 patients with early
and 7 with the late stage of the disease, were evaluated. Five women with vulvar
squamous cell carcinoma (SCC) were also examined. The control group consisted of
9 women who underwent plastic surgery of the vulvar region. Immunohistochemical
staining was performed on formalin-fixed paraffin-embedded tissues samples using
antihuman CD1a antibody (NCL-CD1a-235, Novocastra). RESULTS: Increased numbers of
LC stainings were present in early LS, whereas decreased numbers of these cells
were present in late LS and in SCC compared with the control group. CONCLUSIONS:
This study showed that dysregulation of the SIS may lead to suppression of LCs in
the vulvar epithelium and may be one of the reasons for a higher tendency for
carcinogenesis in the vulvar region.
PMID- 17031467
TI - Mechanisms of tumor escape: role of tumor microenvironment in inducing apoptosis
of cytolytic effector cells.
AB - Spontaneous tumors grow and kill the host unless therapy reduces their mass to a
level where the immune system, it is thought, can control their growth and
diffusion. Indeed, in many instances tumors can reappear, become resistant to
therapy, and escape the host immune response. Many mechanisms of tumor escape
operating in the tumor microenvironment have been proposed: 1) low or absent
expression of molecules on tumor cells involved in tumor target cell recognition;
2) absence of co-stimulation leading to tolerization of T cells; 3) soluble
factors secreted by tumor cells inhibiting T cell response; and 4) regulatory T
cells, myeloid suppressor cells, and stromal cells may impair immune-cell
responses to tumors. Furthermore, tumors can release soluble molecules such as
HLA-I (sHLA-I). This, in turn, reduces T cell-mediated immune response and
induces apoptosis of cytolytic effector cells such as natural killer and CD8(+) T
lymphocytes through the engagement of HLA-I receptors such as CD8 and/or
activating isoforms of the inhibitory receptor superfamily. The release of
soluble ligand for activating receptors, e.g. UL16 binding proteins and/or MHC
class I-related proteins A and B, the natural ligands of NKG2D, may impair
activation, effector cell-mediated recognition, and cytolysis of tumor cells.
Furthermore, the elimination of anti-tumor effector cells may be achieved by
induction of apoptosis consequent to triggering elicited via activating
molecules, such as receptors responsible for natural cytotoxicity, upon their
binding with ligands expressed on tumor cells.
PMID- 17031468
TI - Regulation of cytokine transcription in the context of chromatin.
AB - Understanding the transcriptional regulation of an important class of innate and
adaptive immune system effector molecules, the cytokines, is increasingly
important given the promise cytokine regulation holds for treating various
autoimmune and inflammatory diseases. Studies defining the mechanisms regulating
cytokine transcription initially focused on identifying the cis-acting elements
and trans-acting factors that activate cytokine promoters and enhancers. In the
past, these studies were largely completed in the absence of constraints
instituted by cellular chromatin. Over the past decade it has become obvious that
changes in chromatin accessibility critically control, rather than simply
correlate with, the transcriptional activation of most genes, including
cytokines. Hence candidate transcriptional activators are being re-evaluated for
potency in the context of cellular chromatin. Several distinct mechanisms for
manipulating the generally repressive context of chromatin have been identified
for cytokine genes. Most recently, single nucleotide polymorphisms in cytokine
transcriptional regulatory elements have been shown to play measurable roles in
regulating cytokine levels in the context of naturally selected haplotypes.
Overall, subtle differences in DNA sequence and nucleoprotein complex
composition, including protein post-translational modification, come together in
cell type-specific combinations to explain the normal variation in cytokine
transcription throughout the human populace.
PMID- 17031470
TI - Induction and maintenance of self tolerance: the role of CD4+CD25+ regulatory T
cells.
AB - The immune system responds vigorously to invading pathogens (non-self, foreign),
while remaining unresponsive (tolerant) to the body's own components and
circulating constituents (self). This indifference to self components is a result
of finely orchestrated events of thymic negative selection (central tolerance) of
developing T cells that are autoaggressive combined with those operative in the
periphery (peripheral tolerance) to control the activity of potentially
autoreactive T cells that escaped thymic tolerance. Recently, autoimmune
regulator expressed in the thymus has been identified as a critical mediator of
central tolerance towards tissue-specific antigens. In the periphery, a variety
of regulatory T cells are involved in effecting tolerance. There is immense
interest and excitement about the newly identified subset of CD4(+)CD25(+) T
cells. This is a unique subset of CD4(+) T cells that bear CD25 (IL-2Ralpha
chain) on the cell surface in the naive state and express FoxP3 as a unique
marker. These cells suppress the activity of autoreactive effector T cells
primarily via cell-cell contact. The deficiency and/or altered function of
CD4(+)CD25(+) T cells is associated with autoimmunity. Mice deficient in FoxP3
(scurfy mice) bear an autoimmune phenotype, and human males with mutations in the
corresponding gene express the phenotype of wide-spread autoimmunity, the immune
dysregulation, polyendocrinopathy and enteropathy, and X-linked syndrome. In
vitro expansion of antigen-specific CD4(+)CD25(+) T cells and their adoptive
transfer into patients suffering from autoimmunity is emerging as a promising new
therapeutic approach for these debilitating disorders.
PMID- 17031469
TI - Thalidomide increases in vitro sensitivity of childhood acute lymphoblastic
leukemia cells to prednisolone and cytarabine.
AB - INTRODUCTION: Thalidomide is a derivative of glutamic acid with anti-angiogenic,
anti-inflammatory, immunomodulatory and anti-cancer properties that was found to
inhibit the production of tumor necrosis factor alpha in vitro, stimulate
reactive oxygen species production, and inhibit vascular endothelial growth
factor receptor in acute leukemias. The purpose of this study was to determine
the in vitro activity of thalidomide as a single agent and in combination with
prednisolone or cytarabine in childhood acute lymphoblastic leukemia (ALL).
MATERIALS AND METHODS: Bone marrow samples of 40 childhood ALL patients, normal
lymphocytes of 9 healthy adults, and 3 lymphoid cell lines were evaluated for
cytotoxicity of thalidomide (alone and in combination with prednisolone and
cytarabine) using the MTT assay. Cell cycle analysis was performed by flow
cytometry. RESULTS: Thalidomide as a single agent had weak antileukemic activity
to the childhood ALL samples. However, in the presence of thalidomide the
cytotoxicities of prednisolone and cytarabine were increased 3.3-fold (p<0.001)
and 2.7-fold (p=0.002), respectively. Thalidomide increased apoptosis in
lymphoblasts and modulated the cell-cycle arrest caused by prednisolone, but not
that by cytarabine, in childhood ALL samples. CONCLUSIONS: Thalidomide increases
in vitro the sensitivity of childhood ALL cells to prednisolone and cytarabine.
PMID- 17031471
TI - Air in the carotid canal as a predictor of distal internal carotid artery
laceration.
AB - The authors describe a 25-year old patient with blunt trauma-induced bilateral,
distal segment internal carotid artery (ICA) lacerations, resulting in a left
sided direct carotid-cavernous sinus fistula (CCF) and presenting with massive
oronasal bleeding. The combination of severe oronasal bleeding, with air in the
carotid canal should alarm the treating physician to the presence of a distal
internal carotid artery laceration.
PMID- 17031472
TI - Concise preparation of N(alpha)-Fmoc-N(epsilon)-(Boc, methyl)-lysine and its
application in the synthesis of site-specifically lysine monomethylated peptide.
AB - A concise preparation of N(alpha)-Fmoc-N(epsilon)-(Boc, methyl)-lysine and its
application in the synthesis of site-specifically lysine monomethylated peptide
is described. N (alpha)-Fmoc-N(epsilon)-(Boc, methyl)-lysine is obtained, via
consecutive reductive benzylation and reductive methylation in a one-pot
reaction, followed by debenzylation through catalytic hydrogenolysis and Boc
protection in another one-pot reaction. A peptide containing monomethylated
lysine is successfully synthesized by incorporating N(alpha)-Fmoc-N(epsilon)
(Boc, methyl)-lysine as a building block via solid-phase peptide synthesis.
PMID- 17031473
TI - The five bromotryptophans.
AB - The five regioisomeric bromotryptophans (BrTrps) play an important role in the
life of sponges and lower marine invertebrates. These bromo-amino acids, which
are formed by post-translational modifications, are not found in nature in their
free state, but rather are involved in more complex structures. Any of the BrTrps
can be part of a peptide, a cyclic peptide, an indole alkaloid, an ergot
alkaloid, a macrocycle and others. The present review covers the synthesis,
physical and spectroscopic properties of the five BrTrps. It also describes the
many exiting pharmacological and biological activities played by the BrTrps and
by various secondary metabolites containing brominated tryptophan moieties. Of
special interest are cyclic peptides containing the 2-BrTrp unit, which were
isolated from marine sponges e.g. konbamide, orbiculamide A, the various
keramamides, jaspamide eusynstyelamide and more. Important families of non-cyclic
peptides containing the 6-BrTrp, include the styelins, the conotoxins, the
cathelicidins and several constrained macrocyclic peptides. Many marine secondary
BrTrp-containing, non-peptidic metabolites also display a remarkable spectrum of
bioactivities, which can be harnessed for therapeutic and other purposes.
Examples are: barettin, bromotryptanthrin, tetraacetyl clionamide, cyclocinamide
A, clavicipitic acid, various brominated beta-carbolines. In this review we have
presented the various synthetic routes leading to the preparation of the five
BrTrps and many of its derivatives. Also, we have introduced the reader to many
synthetic routes leading to BrTrp-containing non-peptidic natural products.
Although the functional role of the various compounds in the human body is only
poorly understood, its effects were extensively studied. Almost all of these
compounds exhibit important therapeutic properties e.g. antifungal,
antimicrobial, antihelmintic, insecticidal ichthyotoxic and anticancer activity.
In the present review attempts have been made to provide synopsis, synthesis and
symbiosis of chemical and biological actions, which may provide future guidance
and facilitate further research in this area.
PMID- 17031474
TI - Using ensemble classifier to identify membrane protein types.
AB - Predicting membrane protein type is both an important and challenging topic in
current molecular and cellular biology. This is because knowledge of membrane
protein type often provides useful clues for determining, or sheds light upon,
the function of an uncharacterized membrane protein. With the explosion of newly
found protein sequences in the post-genomic era, it is in a great demand to
develop a computational method for fast and reliably identifying the types of
membrane proteins according to their primary sequences. In this paper, a novel
classifier, the so-called "ensemble classifier", was introduced. It is formed by
fusing a set of nearest neighbor (NN) classifiers, each of which is defined in a
different pseudo amino acid composition space. The type for a query protein is
determined by the outcome of voting among these constituent individual
classifiers. It was demonstrated through the self-consistency test, jackknife
test, and independent dataset test that the ensemble classifier outperformed
other existing classifiers widely used in biological literatures. It is
anticipated that the idea of ensemble classifier can also be used to improve the
prediction quality in classifying other attributes of proteins according to their
sequences.
PMID- 17031475
TI - Cellular thiol status-dependent inhibition of tumor cell growth via modulation of
p27(kip1) translocation and retinoblastoma protein phosphorylation by 1'
acetoxychavicol acetate.
AB - 1'-Acetoxychavicol acetate (ACA) has been shown to inhibit tumor cell growth, but
there is limited information on its effects on cell signaling and the cell cycle
control pathway. In this study, we sought to determine how ACA alters cell cycle
and its related control factors in its growth inhibitory effect in Ehrlich
ascites tumor cells (EATC). ACA caused an accumulation of cells in the G1 phase
and an inhibition of DNA synthesis, which were reversed by supplementation with N
acetylcysteine (NAC) or glutathione ethyl ester (GEE). Furthermore, ACA decreased
hyperphosphorylated Rb levels and increased hypophosphorylated Rb levels. NAC and
GEE also abolished the decease in Rb phosphorylation by ACA. As Rb
phosphorylation is regulated by G1 cyclin dependent kinase and CDK inhibitor
p27(kip1), which is an important regulator of the mammalian cell cycle, we
estimated the amount of p27(kip1) levels by western blotting. Treatment with ACA
had virtually no effect on the amount of p27(kip1) levels, but caused a decrease
in phosphorylated p27(kip1) and an increase in unphosphorylated p27(kip1) as well
as an increase in the nuclear localization of p27(kip1). These events were
abolished in the presence of NAC or GEE. These results suggest that in EATC, cell
growth inhibition elicited by ACA involves decreases in Rb and p27(kip1)
phosphorylation and an increase in nuclear localization of p27(kip1), and these
events are dependent on the cellular thiol status.
PMID- 17031476
TI - Gamma-glutamyl compounds and their enzymatic production using bacterial gamma
glutamyltranspeptidase.
AB - Some amino acids and peptides, which have low solubility in water, become much
more soluble following gamma-glutamylation. Compounds become more stable in the
blood stream with gamma-glutamylation. Several gamma-glutamyl compounds are known
to have favorable physiological effects on mammals. Gamma-glutamylation can
improve taste and can stabilize glutamine in aqueous solution. Because of such
favorable features, gamma-glutamyl compounds are very attractive. However, only a
small number of gamma-glutamyl amino acids have been studied although many other
gamma-glutamyl compounds may have characteristics that will benefit humans. This
is mainly because gamma-glutamyl compounds have not been readily available. An
efficient and simple method of producing various gamma-glutamyl compounds,
especially gamma-glutamyl amino acids, using bacterial gamma
glutamyltranspeptidase has been developed. With this method, modifications of
reactive groups of the substrate and energy source such as ATP are not required,
and a wide-range of gamma-glutamyl compounds can be synthesized. Moreover,
bacterial gamma-glutamyltranspeptidase, a catalyst for this method, is readily
available from the strain over-producing this enzyme. The superiority of
producing gamma-glutamyl compounds with bacterial gamma-glutamyltranspeptidase
over other methods of production is discussed.
PMID- 17031477
TI - Multi-layered network structure of amino acid (AA) metabolism characterized by
each essential AA-deficient condition.
AB - The concentrations of free amino acids in plasma change coordinately and their
profiles show distinctive features in various physiological conditions; however,
their behavior can not always be explained by the conventional flow-based
metabolic pathway network. In this study, we have revealed the interrelatedness
of the plasma amino acids and inferred their network structure with threshold
test analysis and multilevel-digraph analysis methods using the plasma samples of
rats which are fed diet deficient in single essential amino acid. In the inferred
network, we could draw some interesting interrelations between plasma amino acids
as follows: 1) Lysine is located at the top control level and has effects on
almost all of the other plasma amino acids. 2) Threonine plays a role in a hub in
the network, which has direct links to the most number of other amino acids. 3)
Threonine and methionine are interrelated to each other and form a loop
structure.
PMID- 17031478
TI - DNA repair Ku proteins in gastric cancer cells and pancreatic acinar cells.
AB - The DNA repair protein Ku acts as a heterodimer of Ku70 and Ku80 that binds to
the DNA ends, nicks, or single-to-double-strand transition. It has a crucial role
for DNA double-strand-break repair. Either Ku70 or Ku80 itself may have a unique
function that is independent of the other Ku subunit. In this review, the role of
Ku on cell proliferation and apoptosis will be discussed. Ku acts as a regulator
of transcription by interacting with the recombination signal binding protein
Jkappa and the NF-kappaB p50 homodimer to up-regulate p50 expression, which may
regulate the proliferation of gastric cancer cells. Both Ku70 and Ku80
expressions are mediated by constitutively activated NF-kappaB and constitutively
expressed cyclooxygenase-2 in gastric cancer cells, which may be related to
gastric cell proliferation and carcinogenesis. In addition, nuclear loss of Ku
may underlie the mechanism of apoptosis in pancreatic acinar cells after
oxidative stress.
PMID- 17031479
TI - Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease
subjects.
AB - Our aim was to determine changes in free amino acid (FAA) and dipeptide (DP)
concentrations in probable Alzheimer's disease (pAD) subjects compared with
control (CT) subjects using liquid chromatography and electrospray ionization
tandem mass spectrometry (LCMS2). We recruited gender- and age-matched study
participants based on neurological and neuropsychological assessments. We
measured FAAs and DPs in cerebrospinal fluid (CSF), plasma and urine using LCMS2
with selected reaction monitoring (SRM). Imidazole-containing FAAs (histidine,
methyl-histidine), catecholamines (L-DOPA and dopamine), citrulline, ornithine,
glycine and antioxidant DPs (carnosine and anserine) accounted for the major
changes between CT and pAD. Carnosine levels were significantly lower in pAD
(328.4 +/- 91.31 nmol/dl) than in CT plasma (654.23 +/- 100.61 nmol/dl). In
contrast, L-DOPA levels were higher in pAD (1400.84 +/- 253.68) than CT (513.10
+/- 121.61 nmol/dl) plasma. These data underscore the importance of FAA and DP
metabolism in the pathogenesis of AD. Since our data show changes in
antioxidants, neurotransmitters and their precursors, or FAA associated with urea
metabolism in pAD compared with CT, we propose that manipulation of these
metabolic pathways may be important in preventing AD progression.
PMID- 17031480
TI - Synthesis of bis-armed amino acid derivatives via the alkylation of ethyl
isocyanoacetate and the Suzuki-Miyaura cross-coupling reaction.
AB - Two synthetic routes to bis-armed-alpha-amino acid derivatives are described. The
first route involves alkylation of dibromo derivatives with ethyl isocyanoacetate
under phase-transfer catalysis (PTC) conditions. The second route uses a
palladium-mediated Suzuki-Miyaura cross-coupling reaction between a DL-4
boronophenylalanine derivative and aromatic diiodo (or dibromo) compounds.
PMID- 17031481
TI - Selenomethionine induces polyamine biosynthesis in regenerating rat liver tissue.
AB - Our study was undertaken to elucidate the effects of selenomethionine (SeMet) on
polyamine metabolism in regenerating rat liver tissue, as useful model of rapidly
growing normal tissue. We have examined the levels of spermine, spermidine and
putrescine in liver tissue. At the same time we have evaluated the activities of
polyamine oxidase (PAO) and diamine oxidase (DAO), the catabolic enzymes of
polyamine metabolism. The obtained results suggest that polyamine levels in
regenerating liver tissue, at 7(th) day after two-thirds partial hepatectomy,
were higher in comparison with control group. The administration of
selenomethionine to hepatectomized animals during seven days, in a single daily
dose of 2.5 microg/100 g body weight, increases the amount of spermine and
spermidine; the level of putrescine does not change under the influence of SeMet
in regenerating rat liver tissue.PAO activity is lower in regenerating hepatic
tissue than in control group. Supplementation of hepatectomized animals with
SeMet significantly decreases the activity of this enzyme. DAO activity was
significantly higher in hepatectomized and in operated animals treated with SeMet
compared to the sham-operated and control ones. The differential sensitivity
observed in our model of highly proliferating normal tissue to SeMet, compared
with the reported anticancer activity of this molecule is discussed.
PMID- 17031482
TI - Quantification of free amino acids and dipeptides using isotope dilution liquid
chromatography and electrospray ionization tandem mass spectrometry.
AB - Our aim was to develop a liquid chromatography and electrospray ionization tandem
mass spectrometry (LCMS2) method to measure free amino acid (FAA) and dipeptide
(DP) concentrations in biological fluids. We synthesized chloroformate
derivatives of FAA and DP, identified the major precursor ions and used LCMS2 to
obtain the most intense product ions. Using serial dilutions of unlabeled and
labeled standards ([2H3]-L-Dopa, homoarginine, homophenylalanine, [15N]-Glutamine
and [2H3]-methionine), we observed linear relationships in MS response that we
used to calculate the amounts of FAA and DP in biological samples. This method is
sensitive with a limit of detection (LOD) for most of the FAAs and DPs tested in
the 0.05-1 pmol range and is linear over 3-5 orders of magnitude when many
metabolites were measured simultaneously. Reproducibility and between run or
daily variations were <10% for most FAAs and DPs. We applied this method to human
samples and quantitatively measured 21 FAAs and 2 DPs in 200 microl CSF, 31 FAAs
and 6 DPs in 100 microl plasma, and 23 FAAs and 5 DPs in 200 microl urine. These
data demonstrate the potential for using LCMS2 to discover changes in FAA and DP
metabolic pathways that occur during disease pathogenesis.
PMID- 17031483
TI - Antitumor necrosis factor-induced neutropenia: a case report with double positive
rechallenges.
AB - A 50-year-old man with ankylosing spondylitis who developed neutropenia after
treatment of etanercept, with two positive rechallenges, and after the first
infliximab infusion, is described. Although leukopenia and neutropenia related to
etanercept and infliximab have been described as rare adverse events from
clinical trials data, their mechanism of action are unknown. This patient
developed recurrent mild neutropenia after exposition of two different antitumor
necrosis factors; therefore, it seems to be an adverse reaction related to the
therapeutic group. Doctors should be aware of this potentially severe adverse
effect in patients treated with antitumor necrosis factor.
PMID- 17031484
TI - Cervical myelopathy caused by periodontoid synovial pannus in a patient with
psoriatic arthritis: a case report.
AB - The atlantoaxial subluxation and the formation of a synovial periodontoid pannus
are associated with rheumatoid arthritis causing mechanical compression of the
spinal cord and cervical myelopathy. Atlantoaxial subluxation is very rare in
psoriatic arthritis (PsA). Even more rare is the formation of a periodontoid
synovial pannus associated with PsA and signs of myelopathy. In this report,
cervical myelopathy caused by periodontoid synovial pannus in PsA is described.
PMID- 17031485
TI - Poor relationship between joint swelling detected on physical examination and
effusion diagnosed by ultrasonography in glenohumeral joints in patients with
rheumatoid arthritis.
AB - The purpose of this study was to assess the relationship between swelling
detected on physical examination and effusion diagnosed by ultrasonography (US)
in glenohumeral (GH) joints in patients with rheumatoid arthritis (RA). Fifty
consecutive patients with RA entered the study and 20 healthy control persons
formed a control group. Altogether 100 GH joints of the RA patients and 40 of the
controls were evaluated. The clinical assessments were carried out by one doctor
and the US investigations by another, and they were blinded to each other's
results. The clinical examination and US gave similar results in 70 GH joints,
whereas they differed in the remaining 30 GH joints. The kappa coefficient
between these investigations was 0.202, showing poor agreement. These results
showed poor agreement between the clinical assessment of swelling and effusion
detected by US in GH joints. Therefore, US may considerably improve the accuracy
of diagnosis of effusion in GH joints, which usually means synovitis in patients
with RA.
PMID- 17031486
TI - Anterior vaginal wall prolapse and voiding dysfunction in urogynecology patients.
AB - We investigated whether women with and without anterior vaginal wall prolapse
have voiding differences. Women (n=109) who presented to a urogynecology practice
were categorized into two groups based on anterior vaginal wall prolapse: stages
0 and 1 and stages 2, 3, and 4. Women with prolapse were older than the women
without prolapse but the groups were otherwise similar demographically. There was
a higher rate of activity-related urine loss and use of wetness protection
amongst women without prolapse. There was no significant difference for urgency
symptoms or urge incontinence. Urodynamic testing found no significant
differences for maximal flow rate or maximal urethral closing pressures. Postvoid
residual volume and detrusor overactivity were not different but approached
significance. Anterior vaginal wall prolapse of stage 2 or greater was not
associated with urge incontinence or voiding function in this population. Women
without prolapse were more likely to report stress incontinence.
PMID- 17031487
TI - Laparoscopic intraperitoneal repair of high-up urinary bladder fistula: a review
of 12 cases.
AB - Conventional abdominal operations for urinary bladder fistula have limitations
like increased morbidity, more hemorrhage, more postoperative pain, and longer
hospital stay. Laparoscopic repair of bladder fistula was done to explore the
potential role of laparoscopic surgery in this field. Twelve women with
vesicovaginal (11) and vesicouterine (one) fistula, of both gynecological (seven)
and obstetric (five) origins, were treated by laparoscopic intraperitoneal repair
between 1991 and 2004. The bladder wall was mobilized and repaired by interrupted
stitches in single-layer followed by omental interposition. All cases were
completed laparoscopically without any significant intra- or postoperative
complication. Gynecological cases were discharged on the fourth day. Urinary
catheters of all women were removed on the 14th day, and all but one obstetric
fistula (91% success) were closed. Long-term follow-up confirmed the cure.
Laparoscopic repair is an excellent method of repairing urinary bladder fistula
located near the vaginal apex.
PMID- 17031488
TI - Biomesh (Pelvicol) erosion following repair of anterior vaginal wall prolapse.
AB - Sparse information is available regarding erosion following biomesh implantation.
We report two cases of erosion following anterior vaginal wall repair. In both
cases, the operation was performed as a standard cystocele repair where the
collagen Pelvicol mesh was anchored to the pubocervical fascia. Both patients had
signs of erosion shortly after the operation, and both had the mesh removed. In
one patient, the vaginal epithelium healed spontaneously, whereas the other
patient had a delayed healing process. The graft was rejected due to intolerance
to the biomesh or an infection. Our study shows that an erosion following
implantation of a biomesh may be complicated.
PMID- 17031489
TI - Tensile strength and host response towards different polypropylene implant
materials used for augmentation of fascial repair in a rat model.
AB - We compared inflammatory response, fibrosis and biomechanical properties of
different polypropylene materials from one manufacturer (Tyco Healthcare) in a
rat model for primary fascial repair. Full-thickness abdominal wall defects were
primarily repaired using 'overlay' technique. Multifilament implants were
Surgipro SPM and SPMW, the latter a wider-weave type of the former. Monofilament
SPMM implants and polypropylene suture repair (Surgipro II) served as controls.
Explants were evaluated macroscopically and changes in thickness, shrinkage and
tensile strength were measured. Inflammatory and connective tissue response was
assessed on haematoxylin-eosin and Movat stains. Immunohistochemistry was done to
localise rat macrophages/monocytes. Multifilament materials induced a shorter
acute inflammatory response and more pronounced chronic inflammatory reaction
compared to monofilament implants. Macrophages could be found deep in interstices
7.5 by 12.5 microm. No difference in collagen deposition and neovascularisation
was observed. At 90 days time point, explants reconstructed with tighter woven
multifilament SPM were weaker than sutured or SPMM controls. Overall shrinkage of
10% was comparable for all groups.
PMID- 17031490
TI - Neurocognitive functioning in patients with first-episode schizophrenia : results
of a prospective 5-year follow-up study.
AB - To assess the course of neuropsychological (NP) impairment in schizophrenia, 71
patients with first episode (FE) schizophrenia and 71 healthy controls were given
a comprehensive battery of NP tests at index assessment, after a 2-year and after
a 5-year follow-up period. By means of the z-score standardization, summary
scores for verbal intelligence (VBI), spatial organisation (SPT), verbal fluency
(VBF), Verbal learning (VBL), semantic memory (SEM), visual memory (VIM),
delay/retention rate (DEL), short-term memory (STM), visuomotor processing and
attention (VSM) and abstraction/flexibility (ABS) were constructed. FE
schizophrenia patients showed a worse performance compared to controls in all
areas investigated, most pronounced in VSM, SEM and VBL. In the majority of
cognitive domains, an improvement was found over the 5-year follow-up period
without differences between the two groups. However, in VBF patients slightly
deteriorated whilst controls improved and in memory functions patients improved
less compared to controls. When controlling for relevant confounders, neither
conventional nor atypical neuroleptics showed a deleterious influence on NP
performance, except on VBF. Our data suggest that NP impairment is already
present at the onset of the illness and remains stable over the early course of
schizophrenia.
PMID- 17031491
TI - P38 MAPK protects against TNF-alpha-provoked apoptosis in LNCaP prostatic cancer
cells.
AB - PURPOSE: One of the most relevant aspects in cell death regulation is the
signalling of apoptosis by the serine/threonine kinases MAPKs. The aim of this
study was to investigate the effects of TNF-alpha stimulation on MAPK activation,
and the pro- or anti-apoptotic role of these kinases in LNCaP and PC3 cells.
MATERIAL AND METHODS: Treatments were carried out using several TNF-alpha
concentrations, as well as specific pharmacological inhibitors of MAPKs.
Apoptosis rates were evaluated by DAPI staining and flow cytometry. MAPK
phosphorylation/activation was measured by Western blot. RESULTS: TNF-alpha
induced apoptosis in a dose-dependent manner in LNCaP but not in PC3 cells. The
MAPK inhibitors revealed that the apoptotic rate in LNCaP cells increased
significantly following p38 inhibition. The kinase inhibitors failed to cause
changes in apoptosis in PC3 cells. CONCLUSIONS: The potentiation of apoptosis by
p38 inhibition points to this kinase as a possible target for the treatment of
androgen-dependent prostatic cancer.
PMID- 17031492
TI - Adaptor FADD is recruited by RTN3/HAP in ER-bound signaling complexes.
AB - It has been well established that FADD plays a critical role in the membrane
bound death-inducing signaling complexes. Herein, we report that endogenous FADD
could interact with ectopic or endogenous RTN3/HAP. ER-bound RTN3 protein
recruited endogenous FADD to the ER membrane and subsequently initiated caspase-8
cascade, including activation of caspase-8, processing of Bid and release of
cytochrome c from mitochondria. Furthermore, we demonstrated that endogenous FADD
was recruited by ER-bound endogenous RTN3 to the ER membrane under the
tunicamycin stimulation. The dominant negative form of FADD containing DD could
abolish these RTN3 generated events in the caspase-8 cascade. Moreover, we found
that RTN3 induced caspase-9 processing was only partially resulted from caspase-8
activation (data unshown), indicating that multiple caspase cascades participated
in the apoptosis from RTN3 over-expression. Furthermore, NogoB/ASY, a homologue
of RTN3 and a potential RTN3 interacting protein, also associated with FADD and
induced cytochrome c release in a FADD dependent manner.
PMID- 17031493
TI - Caspase-8 dependent TRAIL-induced apoptosis in cancer cell lines is inhibited by
vitamin C and catalase.
AB - TNF-related apoptosis-inducing ligand (TRAIL/ Apo-2L) is a member of the TNF
family of apoptosis-inducing proteins that initiates apoptosis in a variety of
neoplastic cells while displaying minimal or absent cytotoxicity to most normal
cells. Therefore, TRAIL is currently considered a promising target to develop
anti-cancer therapies. TRAIL-receptor ligation recruits and activates pro-caspase
8, which in turn activates proteins that mediate disruption of the mitochondrial
membranes. These events lead to the nuclear and cytosolic damage characteristic
of apoptosis. Here we report that TRAIL-induced apoptosis is mediated by
oxidative stress and that vitamin C (ascorbic acid), a potent nutritional
antioxidant, protects cancer cell lines from apoptosis induced by TRAIL. Vitamin
C impedes the elevation of reactive oxygen species (ROS) levels induced by TRAIL
and impairs caspase-8 activation. We found that the removal of hydrogen peroxide
by extracellular catalase during TRAIL-induced apoptosis also impairs caspase-8
activation. These data suggest that hydrogen peroxide is produced during TRAIL
receptor ligation, and that the increase of intracellular ROS regulates the
activation of caspase-8 during apoptosis. Additionally we propose a mechanism by
which cancer cells might resist apoptosis via TRAIL, by the intake of the
nutritional antioxidant vitamin C.
PMID- 17031494
TI - Chromosome banding in three species of Hypsiboas (Hylidae, Hylinae), with special
reference to a new case of B-chromosome in anuran frogs and to the reduction of
the diploid number of 2n = 24 to 2n = 22 in the genus.
AB - The chromosomes of hylids Hypsiboas albopunctatus, H. raniceps, and H. crepitans
from Brazil were analyzed with standard and differential staining techniques. The
former species presented 2n = 22 and 2n = 23 karyotypes, the odd diploid number
is due to the presence of an extra element interpreted as B chromosome. Although
morphologically very similar to the small-sized chromosomes of the A complement,
the B was promptly recognized, even under standard staining, on the basis of some
characteristics that are usually attributed to this particular class of
chromosomes. The two other species have 2n = 24, which is the chromosome number
usually found in the species of Hypsiboas karyotyped so far. This means that 2n =
22 is a deviant diploid number, resulted from a structural rearrangement,
altering the chromosome number of 2n = 24 to 2n = 22. Based on new chromosome
data, some possibilities were evaluated for the origin of B chromosome in
Hypsiboas albopunctatus, as well as the karyotypic evolution in the genus,
leading to the reduction in the diploid number of 2n = 24 to 2n = 22.
PMID- 17031495
TI - Isolation and characterization of sex chromosome rearrangements generating male
muscle dystrophy and female abnormal oogenesis in the silkworm, Bombyx mori.
AB - In deletion-mapping of W-specific RAPD (W-RAPD) markers and putative female
determinant gene (Fem), we used X-ray irradiation to break the translocation
carrying W chromosome (W( Ze )). We succeeded in obtaining a fragment of the W(
Ze ) chromosome designated as Ze (W), having 3 of 12 W-RAPD markers (W-Bonsai, W
Yukemuri-S, W-Yukemuri-L). Inheritance of the Ze (W) fragment by males indicates
that it does not include the Fem gene. On the basis of these results, we
determined the relative positions of W-Yukemuri-S and W-Yukemuri-L, and we
narrowed down the region where Fem gene is located. In addition to the Ze (W)
fragment, the Z chromosome was also broken into a large fragment (Z(1)) having
the +( sch ) (1-21.5) and a small fragment (Z(2)) having the +( od ) (1-49.6).
Moreover, a new chromosomal fragment (Ze (W)Z(2)) was generated by a fusion event
between the Ze (W) and the Z(2) fragments. We analyzed the genetic behavior of
the Z(1) fragment and the Ze (W)Z(2) fragment during male (Z/Z(1) Ze (W)Z(2)) and
female (Z(1) Ze (W)Z(2)/W) meiosis using phenotypic markers. It was observed that
the Z(1) fragment and the Z or the W chromosomes separate without fail. On the
other hand, non-disjunction between the Ze (W)Z(2) fragment and the Z chromosome
and also between the Ze (W)Z(2) fragment and the W chromosome occurred.
Furthermore, the females (2A: Z/Ze (W)Z(2)/W) and males (2A: Z/Z(1)) resulting
from non-disjunction between the Ze (W)Z(2) fragment and the W chromosome had
phenotypic defects: namely, females exhibited abnormal oogenesis and males were
flapless due to abnormal indirect flight muscle structure. These results suggest
that Z(2) region of the Z chromosome contains dose-sensitive gene(s), which are
involved in oogenesis and indirect flight muscle development.
PMID- 17031496
TI - Bayesian analysis of paired survival data using a bivariate exponential
distribution.
AB - We consider a Bayesian analysis method of paired survival data using a bivariate
exponential model proposed by Moran (1967, Biometrika 54:385-394). Important
features of Moran's model include that the marginal distributions are exponential
and the range of the correlation coefficient is between 0 and 1. These contrast
with the popular exponential model with gamma frailty. Despite these nice
properties, statistical analysis with Moran's model has been hampered by lack of
a closed form likelihood function. In this paper, we introduce a latent variable
to circumvent the difficulty in the Bayesian computation. We also consider a
model checking procedure using the predictive Bayesian P-value.
PMID- 17031497
TI - A flexible semiparametric transformation model for survival data.
AB - I suggest an extension of the semiparametric transformation model that specifies
a time-varying regression structure for the transformation, and thus allows time
varying structure in the data. Special cases include a stratified version of the
usual semiparametric transformation model. The model can be thought of as
specifying a first order Taylor expansion of a completely flexible baseline.
Large sample properties are derived and estimators of the asymptotic variances of
the regression coefficients are given. The method is illustrated by a worked
example and a small simulation study. A goodness of fit procedure for testing if
the regression effects lead to a satisfactory fit is also suggested.
PMID- 17031498
TI - Dynamic survival models with spatial frailty.
AB - In many survival studies, covariates effects are time-varying and there is
presence of spatial effects. Dynamic models can be used to cope with the
variations of the effects and spatial components are introduced to handle spatial
variation. This paper proposes a methodology to simultaneously introduce these
components into the model. A number of specifications for the spatial components
are considered. Estimation is performed via a Bayesian approach through Markov
chain Monte Carlo methods. Models are compared to assess relevance of their
components. Analysis of a real data set is performed, showing the relevance of
both time-varying covariate effects and spatial components. Extensions to the
methodology are proposed along with concluding remarks.
PMID- 17031499
TI - A semiparametric additive rates model for recurrent event data.
AB - Recurrent event data often arise in biomedical studies, with examples including
hospitalizations, infections, and treatment failures. In observational studies,
it is often of interest to estimate the effects of covariates on the marginal
recurrent event rate. The majority of existing rate regression methods assume
multiplicative covariate effects. We propose a semiparametric model for the
marginal recurrent event rate, wherein the covariates are assumed to add to the
unspecified baseline rate. Covariate effects are summarized by rate differences,
meaning that the absolute effect on the rate function can be determined from the
regression coefficient alone. We describe modifications of the proposed method to
accommodate a terminating event (e.g., death). Proposed estimators of the
regression parameters and baseline rate are shown to be consistent and
asymptotically Gaussian. Simulation studies demonstrate that the asymptotic
approximations are accurate in finite samples. The proposed methods are applied
to a state-wide kidney transplant data set.
PMID- 17031500
TI - Computerized adaptive testing of diabetes impact: a feasibility study of
Hispanics and non-Hispanics in an active clinic population.
AB - BACKGROUND: Diabetes is a leading cause of death and disability in the US and is
twice as common among Hispanic Americans as non-Hispanics. The societal costs of
diabetes provide an impetus for developing tools that can improve patient care
and delay or prevent diabetes complications. METHODS: We implemented a
feasibility study of a Computerized Adaptive Test (CAT) to measure diabetes
impact using a sample of 103 English- and 97 Spanish-speaking patients (mean age
= 56.5, 66.5% female) in a community medical center with a high proportion of
minority patients (28% African-American). The 37 items of the Diabetes Impact
Survey were translated using forward-backward translation and cognitive
debriefing. Participants were randomized to receive either the full-length tool
or the Diabetes-CAT first, in the patient's native language. RESULTS: The number
of items and the amount of time to complete the survey for the CAT was reduced to
one-sixth the amount for the full-length tool in both languages, across disease
severity. Confirmatory Factor Analysis confirmed that the Diabetes Impact Survey
is unidimensional. The Diabetes-CAT demonstrated acceptable internal consistency
reliability, construct validity, and discriminant validity in the overall sample,
although subgroup analyses suggested that the English sample data evidenced
higher levels of reliability and validity than the Spanish sample and issues with
discriminant validity in the Spanish sample. Differential Item Function analysis
revealed differences in responses tendencies by language group in 3 of the 37
items. Participant interviews suggested that the Spanish-speaking patients
generally preferred the paper survey to the computer-assisted tool, and were
twice as likely to experience difficulties understanding the items. CONCLUSIONS:
While the Diabetes-CAT demonstrated clear advantages in reducing respondent
burden as compared to the full-length tool, simplifying the item bank will be
necessary for enhancing the feasibility of the Diabetes-CAT for use with low
literacy patients.
PMID- 17031501
TI - Testing the interval-level measurement property of multi-item visual analogue
scales.
AB - BACKGROUND: Conditions were studied that may invalidate health-state values
derived from the visual analogue scale (VAS). METHODS: Respondents were asked to
place cards with descriptions of EQ-5D health states on a 20 cm EuroQol VAS and
modified versions of it, positioning them such that the distances between the
states reflect their valuation for these states. Anchor-point bias was examined
using the standard EuroQol VAS (n = 212) and a modified version (n = 97) with a
different lower anchor. Context bias was examined in another group of respondents
(n = 112) who valued three different sets of EQ-5D health states. Marker bias was
studied in yet another group of respondents (n = 100) who placed the same EQ-5D
states on the standard EuroQol VAS and on a modified VAS without anchors,
categories, or measurement markers. RESULTS: No indication for the existence of
the anchor-point and the marker bias was found. However, the VAS valuations were
significantly affected by the context of the set of health states in the scaling
task. CONCLUSION: Advanced methodologies should be incorporated in VAS valuation
studies to deal with the context bias.
PMID- 17031502
TI - The ORTHO BC-SAT--a satisfaction questionnaire for women using hormonal
contraceptives.
AB - OBJECTIVE: To assess the reliability and validity of the ORTHO Birth Control
Satisfaction Assessment Tool (ORTHO BC-SAT). DESIGN: 339 women using 1 of 4
hormonal birth control methods (oral contraceptives, transdermal patch, vaginal
ring, injections), completed the questionnaire 1-2 times. MATERIALS AND METHODS:
The questionnaire was developed based on findings from the literature, focus
groups, and interviews. Internal consistency reliability, test-retest
reliability, construct validity, and known groups validity were evaluated.
RESULTS: Based on variable clustering, 8 domains were identified (Ease of
Use/Convenience, Compliance, Lifestyle Impact, Symptom/Side Effect Bother,
Menstrual Impact, Future Fertility Concerns, Assurance/Confidence, Overall
Satisfaction). Internal consistency reliability was demonstrated with Cronbach's
alpha values ranging from 0.70 to 0.89. All multi-item scales reported acceptable
test-retest reliability (0.79-0.87). Construct validity was demonstrated by
support of a hypothesized pattern of correlations. Known groups validity was
confirmed by examining scale scores of women categorized by levels of symptom
bother. As expected, women with the least amount of bother reported higher scores
on all satisfaction scales than those with higher bother (p < 0.0001), except on
Future Fertility Concerns (p = 0.27). CONCLUSION: Our results support the
reliability and validity of the ORTHO BC-SAT. It may be used in future studies to
evaluate satisfaction among hormonal contraceptive users.
PMID- 17031503
TI - The clinical significance of adaptation to changing health: a meta-analysis of
response shift.
AB - AIMS: When individuals experience changes in their health states, they may alter
their internal standards, values, or conceptualization of quality of life (QOL).
Such 'response shifts' can affect or distort QOL outcome measurement, which is of
particular concern when evaluating medical or psychosocial interventions.
Although clinicians and researchers acknowledge the occurrence of response
shifts, little is known about the magnitude and clinical significance of those
effects. To fill this gap in knowledge about response shift phenomena, we
performed a meta-analysis on published QOL articles on response shift. METHODS:
Extensive literature searches and multiple contacts with researchers yielded a
collection of 494 articles for potential reviewing. We retained only published
longitudinal studies that measured response shift, resulting in 26, of which 19
reported the requisite data for computing an effect size (ES). We calculated and
compared the ESs for each study with regard to potential moderator variables: the
QOL domains measured, disease group investigated, sample size, and response shift
method used. We rated studies for quality to allow ES weighting. RESULTS: When we
examined ES absolute values, we found that ES magnitude was small, with the
largest ESs detected for fatigue, followed by global QOL, physical role
limitation, psychological well-being, and pain (mean absolute value(ES(weighted))
= 0.32, 0.30, 0.24, 0.12, and 0.08, respectively). ESs varied considerably in
direction. Aggregating raw ES scores over all studies led to positive and
negative values canceling each other out (mean directional ES(weighted) = 0.17,
0.02, -0.01, 0.06, and 0.02, respectively). We found little evidence of an effect
for the moderator variables examined. CONCLUSIONS: A definitive conclusion on the
clinical significance of response shift cannot currently be drawn from existing
studies. For a number of reasons, ES estimates were primarily based on then-test
results, a method that is not without criticism, such as its susceptibility to
recall bias. We recommend a standardized approach for reporting results of future
response shift research to advance the field and to facilitate interpretation and
comparisons across studies.
PMID- 17031504
TI - Fibromuscular dysplasia of the renal arteries: a radiological review.
AB - Fibromuscular dysplasia is the most common cause of renovascular hypertension in
young patients. Digital subtraction angiography is still the best investigation
used to determine the location, extent and complication of renal artery
involvement. String of beads appearance (reflecting multiple stenoses),
aneurysms, focal or tubular stenosis are classic angiographic appearances. The
aim of this pictorial essay is to illustrate the various imaging findings of
renal artery fibromuscular dysplasia.
PMID- 17031505
TI - Endothelial dysfunction in geriatric diabetic patients: the role of
microalbuminuria in elderly type 2 diabetic patients? A randomized controlled
study.
AB - BACKGROUNDS/AIMS: Microalbuminuria is considered a marker of extensive
endothelial dysfunction and is associated with excess of other cardiovascular
risk factors. Our aim is to assess the importance of the presence of
microalbuminuria in elderly diabetic patients. METHODS: A total of 40
normotensive elderly type 2 diabetic patients of both genders with mean age >65
years were randomly included and were further subdivided according to the
presence of persistent microalbuminuria into microalbuminuric and
normoalbuminuric groups. PATIENTS AND METHODS: All patients in both groups were
subjected to thorough clinical and laboratory investigations including the assay
of serum thrombomodulin (TM) and glycosylated hemoglobin level. Early-morning
midstream urine samples were evaluated for levels of beta 2 microglobulin, alpha
1 microglobulin, TM, and N-acetyl-beta-D-glucosaminidase (NAG). RESULTS: There
was no significant difference between both groups regarding the clinical
demographic characteristics. There were statistically significant higher values
for glycosylated hemoglobin percentage, serum triglycerides and serum TM and
urinary B2 microglobulin, urinary alpha 1 microglobulin, urinary NAG and urinary
thrombomodulin in microalbuminuric group in comparison to normoalbuminuric group
(P < 0.05). CONCLUSION: Microalbuminuria is associated with markers of
endothelial dysfunction in elderly normotensive type 2 diabetic patients. We
recommend incorporation of periodic testing for microalbuminuria in this sector
of patients.
PMID- 17031506
TI - Unexplained hematuria during pregnancy: right-sided nutcracker phenomenon.
AB - We report a case of hematuria in a pregnant patient caused by right renal vein
hypertension, as a result of compression of right renal, the inferior caval and
the right gonadal veins because of posterior displacement of the pancreas caused
by the presence of the gravid uterus. Hematuria resolved after a cesarean
delivery. This condition has not been, to our knowledge, previously described.
PMID- 17031507
TI - Suspended particulate matter distribution in rural-industrial Satna and in urban
industrial South Delhi.
AB - An air quality sampling program was designed and implemented to collect the
baseline concentrations of respirable suspended particulates (RSP = PM10), non
respirable suspended particulates (NRSP) and fine suspended particulates (FSP =
PM2.5). Over a three-week period, a 24-h average concentrations were calculated
from the samples collected at an industrial site in Southern Delhi and compared
to datasets collected in Satna by Envirotech Limited, Okhla, Delhi in order to
establish the characteristic difference in emission patterns. PM2.5, PM10, and
total suspended particulates (TSP) concentrations at Satna were 20.5 +/- 6.0,
102.1 +/- 41.1, and 387.6 +/- 222.4 microg m(-3) and at Delhi were 126.7 +/-
28.6, 268.6 +/- 39.1, and 687.7 +/- 117.4 microg m(-3). Values at Delhi were well
above the standard limit for 24-h PM2.5 United States National Ambient Air
Quality Standards (USNAAQS; 65 microg m(-3)), while values at Satna were under
the standard limit. Results were compared with various worldwide studies. These
comparisons suggest an immediate need for the promulgation of new PM2.5
standards. The position of PM10 in Delhi is drastic and needs an immediate
attention. PM10 levels at Delhi were also well above the standard limit for 24-h
PM10 National Ambient Air Quality Standards (NAAQS; 150 microg m(-3)), while
levels at Satna remained under the standard limit. PM2.5/PM10 values were also
calculated to determine PM2.5 contribution. At Satna, PM2.5 contribution to PM10
was only 20% compared to 47% in Delhi. TSP values at Delhi were well above, while
TSP values at Satna were under, the standard limit for 24-h TSP NAAQS (500 microg
m(-3)). At Satna, the PM10 contribution to TSP was only 26% compared to 39% in
Delhi. The correlation between PM10, PM2.5, and TSP were also calculated in order
to gain an insight to their sources. Both in Satna and in Delhi, none of the
sources was dominant a varied pattern of emissions was obtained, showing the
presence of heterogeneous emission density and that nonrespirable suspended
particulate (NRSP) formed the greatest part of the particulate load.
PMID- 17031508
TI - Levels of PAHs in the soils of Belgrade and its environs.
AB - Polycyclic aromatic hydrocarbons (PAHs) were analysed in 39 soil samples (0-10 cm
upper layer) collected in Belgrade, the capital of Serbia. The sampling sites
were randomly selected from urban, urban/recreational and rural areas; the
samples were collected in April and December 2003 and July and October 2004. The
sum of the 16 PAHs corresponding to the recreational zone (298 microg/kg) was
close to the urban zone (375 microg/kg). Mean soil SigmaPAH concentration from
rural areas was 18 microg/kg dry weight. Comparing to values observed in the
urbanized locations around the world, the overall levels of PAHs in this study
are low. The PAH ratios obtained pointed to a domination of pyrogenically formed
PAHs in the examined soils. The dominant PAHs in soil samples in urban zones were
fluoranthene, benz[a]anthracene, phenanthrene and pyrene, mostly emitted from
noncatalyst vehicles which are still in use in Serbia. The total carcinogenic
potency for each sampling site was calculated. Regardless of the used
carcinogenic activity factors, carcinogenic potency of 7 sites were 3-9 times
higher than the reference ones indicating the increased carcinogenic burden of
soils from these sites.
PMID- 17031509
TI - Concentrations and modes of occurrence of trace elements in the Late Permian
coals from the Puan Coalfield, southwestern Guizhou, China.
AB - The concentration, mode of occurrence, and origin of trace elements in the Late
Permian coals from the Puan Coalfield, southwestern Guizhou, China, were examined
using inductively coupled plasma-mass spectrometry (ICP-MS), X-ray fluorescence
(XRF), cold-vapor atomic absorption spectrometry (CV-AAS), ion-selective
electrode method (ISE), sequential chemical extraction procedure (SCEP), scanning
electron microscopy equipped with energy-dispersive X-ray (SEM-EDX), and optical
microscope. Results show that minerals in the No. 2 Coal from the Puan Coalfield
were mainly made up of epigenetic pyrite of low-temperature hydrothermal fluid
origin and kaolinite of detrital terrigenous origin. Elements including As (36.9
microg/g), Cd (10.2 microg/g), Cr (167.3 microg/g), Cu (365.4 microg/g), Hg (2.82
microg/g), Mo (92.6 microg/g), Ni (82.6 microg/g), Pb (184.6 microg/g), Se (6.23
microg/g), Zn (242.3 microg/g), and U (132.7 microg/g) are significantly enriched
in the No. 2 Coal from the Puan Coalfield. However, concentrations of trace
elements in the other four coals, the No. 1, No. 8, No. 11, and No. 18 Coals,
were close to the usual ranges found for Guizhou of China, China, and USA.
Results of SEM-EDX and SCEP showed that As, Cd, Hg, Mo, Ni, Pb, and Zn occur
mainly in veined pyrite, while Cr, Cu, and U distribute mainly in kaolinite,
indicating that the low-temperature hydrothermal fluid and detrital materials of
terrigenous origin are the main contributors to the enrichment of these trace
elements in the No. 2 Coal.
PMID- 17031510
TI - Long-term safety and efficacy of infliximab therapy in refractory uveitis due to
Behcet's disease.
AB - PURPOSE: To evaluate the long-term safety and efficacy of infliximab therapy for
refractory uveitis associated with Behcet's disease (BD). METHODS: We
prospectively enrolled six patients who failed to respond to conventional
immunosuppressive treatment. Infliximab infusions (5 mg/kg) were administered at
weeks 0, 2, 6, and then every 8 weeks. The outcome variables were visual acuity,
control of inflammation, reduction of macular edema, tapering of
immunosuppressive therapy, and adverse effects. RESULTS: The follow-up period
ranged from 16 to 36 months (mean +/- SD, 23 +/- 7.4 months). The number of
infliximab infusions ranged from 10 to 23 (14 +/- 4.6). By the 2-month follow-up,
all patients had achieved remission, the cystoid macular edema had resolved, and
visual acuity had improved dramatically. Throughout the follow-up period, three
patients remained attack-free. One patient had one relapse, and another patient
had two relapses before the scheduled infusions; all three relapses resolved
rapidly after the subsequent infusion. One patient developed five relapses, and
infusions at 6-week intervals were necessary to achieve sustained remission. At
the end of the follow-up period, visual acuity improved in five patients.
Concomitant immunosuppressive therapy was substantially reduced. Antinuclear
antibodies developed in two patients who received 17 and 23 infusions. No major
adverse effects requiring withdrawal of infliximab were observed. CONCLUSION:
Infliximab is efficient and safe for long-term treatment of refractory uveitis
associated with BD. Repeated infusions are required to maintain long-term
remission.
PMID- 17031511
TI - A novel drought-inducible gene, ATAF1, encodes a NAC family protein that
negatively regulates the expression of stress-responsive genes in Arabidopsis.
AB - NAC proteins are plant-specific transcriptional regulators. ATAF1 was one of the
first identified NAC proteins in Arabidopsis. In present study, we characterized
the ATAF1 expression and biological function in response to water deficit stress.
ATAF1 mRNA expression was strongly induced by dehydration and abscisic acid (ABA)
treatment, but inhibited by water treatment, suggesting a general role in drought
stress responses. Transient expression analysis in onion epidermal cells
indicated the nuclear localization for the ATAF1::GFP fusion protein. Yeast
transactivation analysis showed that ATAF1 had ability to activate reporter gene
expression. Furthermore, domain deletion analysis revealed that the ATAF1
transactivation activity was conferred by its C-terminal domain. When ATAF1 gene
was knocked out by T-DNA insertions, Arabidopsis ataf1-1 and ataf1-2 mutants
displayed a recovery rate about seven times higher than wild-type plants in
drought response test. This ataf1 phenotype was coincident with the enhanced
expression of stress responsive marker genes, such as COR47, ERD10, KIN1, RD22
and RD29A under drought stress. Above evidences suggest that ATAF1, as a
transcriptional regulator, negatively regulates the expression of stress
responsive genes under drought stress in Arabidopsis.
PMID- 17031512
TI - ABI4 mediates the effects of exogenous trehalose on Arabidopsis growth and starch
breakdown.
AB - The disaccharide trehalose has dramatic effects on plant metabolism, growth and
development. Arabidopsis seedlings grown on trehalose-containing medium without
sucrose display increased expression of the starch synthesis gene ApL3, hyper
accumulation of starch in the cotyledons and inhibition of root growth. Here we
show that the ABI4 transcription factor mediates the effects of trehalose on
starch metabolism and growth, independently of abscisic acid (ABA) synthesis and
hexokinase (HXK1) signaling. Surprisingly, although the abi4 mutation partially
rescued trehalose inhibition of root elongation, ApL3 expression levels were
still enhanced. Gene expression analysis suggests that trehalose affects both
starch synthesis and starch breakdown. The expression of genes involved in starch
breakdown, such as SEX1 and the beta-amylase gene BMY8/BAM3, was strongly down
regulated in WT plants grown on trehalose but not in abi4 mutants. Addition of
trehalose to liquid-grown WT seedlings also significantly reduced SEX1 expression
after 6 h. Bypassing the need for starch breakdown by growth in continuous light
or addition of sucrose rescued root growth on trehalose medium similar to the
abi4 mutation. These results suggest that inhibition of starch mobilization
rather than increased synthesis is involved in growth inhibition by exogenous
trehalose. Trehalose also significantly enhanced ABI4 expression but reduced its
sucrose induction, providing a possible molecular mechanism for the trehalose
effect on plant gene expression and growth.
PMID- 17031513
TI - The late pollen actins are essential for normal male and female development in
Arabidopsis.
AB - In angiosperms the late pollen actins (LPAs) are strongly expressed in mature
pollen and pollen tubes and at much lower levels in ovules. Four Arabidopsis
lines with homozygous knockout mutations in the four individual LPA genes
displayed normal flowers, pollen, and seed set. However, when all four LPAs were
silenced simultaneously with a single RNA interference (RNAi) construct targeting
the 3'UTR of each mRNA, obvious reproductive defects were observed. Western
analysis of various Late Pollen actin RNA interference (LPRi) epialleles showed
total LPA protein and RNA expression levels were knocked down from 0% to 95%
compared to wild-type levels. Reciprocal crosses with the RNAi lines demonstrated
that lowered LPA expression was associated with defects in both male and female
fertility. Strong epialleles showed significant reductions in normal silique and
seed production and were nearly sterile. Dissection of the siliques from moderate
LPRi epialleles revealed many unfertilized ovules, increased numbers of aborted
seeds, and decreased numbers of healthy seeds. Microscopic analysis of LPRi
pollen indicated that the pollen shape and size were normal, but pollen
germinated poorly. While multiple LPA genes may have some functional redundancy,
the combined expression of multiple LPA genes appears essential to normal male
and female reproductive development.
PMID- 17031514
TI - The tumor-growth inhibitory activity of flavanone and 2'-OH flavanone in vitro
and in vivo through induction of cell cycle arrest and suppression of cyclins and
CDKs.
AB - Natural products, including flavonoids, are suggested to be involved in the
protective effects of fruits and vegetables against cancer. However, studies
concerning the effect of flavonoids frequently lacked data regarding to
flavanones. In this study, we investigated the inhibitory effect of flavanone
compounds, including flavanone, 2'-OH flavanone, 4'-OH flavanone, 6-OH flavanone,
naringin and naringenin, on cell growth of various cancer cells. We determined
that flavanone and 2'-OH flavanone inhibited cell growth of A549, LLC, AGS, SK
Hepl and HA22T cancer cells, while other flavanones showed little or no
inhibition. We evaluated growth-inhibitory activity of flavanone and 2'-OH
flavanone against highly proliferative human lung cancer cells (A549) via
anchorage-independent and -dependent colony formation assay, and further showed
that treatment of flavanone resulted in a G1 cell cycle arrest with reduction of
cyclin D, E and cyclin-dependent kinase (CDK) 2, while treatment of 2'-OH
flavanone led to a G2/M phase accumulation with reduction of cyclin B, D and
Cdc2. Moreover, we demonstrated the improvement effect of flavanone and 2'-OH
flavanone with anti-cancer drug, doxorubicin, on A549 cells. Finally, flavanone
and 2'-OH flavanone were evidenced by its inhibition on the growth of A549 and
Lewis lung carcinoma cells in vivo.
PMID- 17031515
TI - In vitro modeling of the structure-activity determinants of anthracycline
cardiotoxicity.
AB - Doxorubicin and other anthracyclines rank among the most effective anticancer
drugs ever developed. Unfortunately, the clinical use of anthracyclines is
limited by a dose-related life-threatening cardiotoxicity. Understanding how
anthracyclines induce cardiotoxicity is essential to improve their therapeutic
index or to identify analogues that retain activity while also inducing less
severe cardiac damage. Here, we briefly review the prevailing hypotheses on
anthracycline-induced cardiotoxicity. We also attempt to establish cause-and
effect relations between the structure of a given anthracycline and its
cardiotoxicity when administered as a single agent or during the course of
multiagent chemotherapies. Finally, we discuss how the hypotheses generated by
preclinical models eventually translate into phase I-II clinical trials.
PMID- 17031516
TI - Frailty modelling of colorectal cancer incidence in Norway: indications that
individual heterogeneity in risk is related to birth cohort.
AB - Some cancer types level off or decrease in incidence at older age groups, not
following the Weibull hazard rate. This stagnation can be explained by the
frailty model, which describes the population effect of mixing individuals who
are susceptible, with high risk of cancer, with those that are "non-susceptible",
with a low risk of cancer even in the oldest age groups. The aim of the study was
to apply a frailty model on colorectal cancer incidence data for the Norwegian
population aged 40-99 years, diagnosed 1956-2000. The model provided an
acceptable fit to the data. The estimated proportion of susceptibles increased
from about 5% to about 24% from the first cohort (1851-1855) to the last cohort
(1946-1950), in line with the rise in incidence of the disease during this
period. According to the frailty modelling, the estimated number of genetic
events necessary for a malignant lesion to develop in the colorectum is seven to
eight, which accords with the present knowledge regarding colorectal
carcinogenesis. The frailty phenomenon may thus be present in this cancer form.
The findings indicate that it is possible to model the development of colorectal
cancer in the population based on large heterogeneity in risk between
individuals, in such a manner that a small group of individuals are susceptible
to develop the disease, whereas the remaining majority have a low susceptibility.
PMID- 17031517
TI - Classification of surgical procedures for epidemiologic assessment of sporadic
Creutzfeldt-Jakob disease transmission by surgery.
AB - BACKGROUND: In this preparatory phase of a case-control study, we propose and
evaluate a new tool for classifying surgical procedures (SPs) in categories
useful for epidemiologic research on surgical transmission of sporadic
Creutzfeldt-Jakob disease (sCJD). METHODS: All SPs reported to the Swedish
National Hospital Discharge Registry in the period 1974-2002, and undergone by
212 Swedish patients with registered diagnosis of CJD at death, hospital
discharge or notification, in the period 1987-2002, 1060 age-, sex- and residence
matched controls and 1340 randomly chosen population controls, were reclassified
into one of six categories of hypothetical transmission risk level. For that
purpose the following two attributes were used: non-disposable instruments
involved; and highest assigned ad-hoc risk level for four tissues or anatomical
structures contacting such instruments. RESULTS: A total of 1170 different SP
codes were reclassified as follows: 3.1% in the high-risk, 59.1% in the lower
risk, 24.4% in the lowest-risk, and 2.1% in the no-risk groups, with 11.3%
procedures negatively defined by rubric as "other than..." being assigned to two
spurious diluted-high and diluted-lower risk categories. The high-risk group
mainly comprised neurosurgical (53%) and ophthalmic (39%) procedures. Sensitivity
of neurosurgery and of ophthalmic surgery excluding neurosurgery, for the high-
and diluted-high risk vs. other categories was 46% and 84%, while specificity was
98% and 95%, respectively. Sensitivity analysis based on these indices revealed
that non-significant odds ratio effects of 1.4 and 1.3 for neurosurgery and
ophthalmic surgery corresponded to statistically significant values of 5.1 after
reclassification. CONCLUSIONS: This classification might contribute to quantify
effects masked by use of body-system SP-categories in case-control studies on
sCJD transmission by surgery.
PMID- 17031518
TI - Effect of genetic variation in the leptin gene promoter and the leptin receptor
gene on obesity risk in a population-based case-control study in Spain.
AB - There are no good genetic markers for incorporating the study of genetic
susceptibility to obesity in epidemiological studies. In animal models, the
leptin (LEP) and the leptin receptor (LEPR) genes have been shown to be very
important in obesity because leptin functions as a negative feedback signal in
regulating body-weight through reducing food intake and stimulating energy
expenditure. In humans, several polymorphisms in these genes have been described.
However, their association with obesity is still very controversial because there
are no good case-control studies designed to specifically test this association.
Our objective has been to conduct a population-based case-control study to
estimate the risk of obesity arising from the -2548G > A and Q223R polymorphisms
in the LEP and LEPR genes, respectively. 303 obese cases (101 men and 202 women)
and 606 controls (202 men and 404 women) were selected from a Spanish
Mediterranean population. Genetic, clinical and life-style characteristics were
analyzed. No association was found between the -2548G > A polymorphism and
obesity. However, the Q223R variant was significantly associated with obesity in
a recessive model, the RR genotype being more prevalent in controls than in obese
subjects. The inverse association between the Q223R polymorphism and obesity (OR
= 0.62; 95% CI: 0.39-0.99) remained significant even after additional adjustment
for education, tobacco smoking, alcohol, physical activity, origin of the obese
patient, and the -2548G > A polymorphism in the LEP gene (OR = 0.54; 95% CI: 0.32
0.89). In conclusion, the -2548G > A polymorphism is not a relevant obesity
marker in this Mediterranean population, although Q223R does seen to be so.
PMID- 17031519
TI - Incidence of bacterial and viral enteric pathogens in children with
gastroenteritis over a one year-period, in Attica, Greece.
PMID- 17031520
TI - Epidemiological and virological features of HBV infection in HIV-2 infected
patients living in southeastern France.
AB - We studied HBV infection in 34 HIV-2-infected patients followed-up in Marseilles.
Ten (29%) patients were chronically-infected with HBV, which represents a three
times higher rate than in HIV-1-infected patients in Europe. HBV occult infection
was diagnosed in two patients. HBV genotype E was found in seven patients; its
specificities and the reciprocal influence of HIV-2/HBV-co-infection remain to be
evaluated.
PMID- 17031521
TI - The biobank of the Norwegian Mother and Child Cohort Study: a resource for the
next 100 years.
AB - INTRODUCTION: Long-term storage of biological materials is a critical component
of any epidemiological study. In designing specimen repositories, efforts need to
balance future needs for samples with logistical constraints necessary to process
and store samples in a timely fashion. OBJECTIVES: In the Norwegian Mother and
Child Cohort Study (MoBa), the Biobank was charged with long-term storage of more
than 380,000 biological samples from pregnant women, their partners and their
children for up to 100 years. METHODS: Biological specimens include whole blood,
plasma, DNA and urine; samples are collected at 50 hospitals in Norway. All
samples are sent via ordinary mail to the Biobank in Oslo where the samples are
registered, aliquoted and DNA extracted. DNA is stored at -20 degrees C while
whole blood, urine and plasma are stored at -80 degrees C. RESULTS: As of July
2006, over 227,000 sample sets have been collected, processed and stored at the
Biobank. Currently 250-300 sets are received daily. An important part of the
Biobank is the quality control program. CONCLUSION: With the unique combination
of biological specimens and questionnaire data, the MoBa Study will constitute a
resource for many future investigations of the separate and combined effects of
genetic, environmental factors on pregnancy outcome and on human morbidity,
mortality and health in general.
PMID- 17031522
TI - Quantitative immunogold study of increased expression of metallothionein-I/II in
the brain perivascular areas of diabetic scrapie-infected mice.
AB - Quantitative immunogold procedure was used to study the distribution of
metallothionein I/II (MT-I/II) at the ultrastructural level in the perivascular
areas, including microvascular endothelial cells (ECs) and astrocytes with their
perivascular end-feet, in brains of scrapie-infected hyperglycemic (diabetic) and
normoglycemic (non-diabetic) mice. Samples of the fronto-parietal cortex obtained
from diabetic and non-diabetic scrapie-infected, as well as from non-infected
(control) SJL/J mice, were processed for immunocytochemical examination. In
control mice, the labelling of the ECs was of low intensity, restricted to few
immunogold particles in the cytoplasm. More intense labelling was present in the
cytoplasm of astrocytic perivascular processes and perikarya, where it was
associated with endoplasmic reticulum and fibrils. A few immunosignals were also
present inside the nuclei of astrocytes. In diabetic mice the labelling of the EC
cytoplasm was slightly increased, whereas in the cytoplasm of perivascular
processes and pericarya of astrocytes, including their nuclei, there was
significant enhancement of labelling. In these cells the density of immunosignals
was highest in the areas of cytoplasm containing bundles of fibrils. In non
diabetic, scrapie-infected mice the intensity of immunolabelling was higher than
in control mice but slightly lower than in diabetic mice. These results are
similar to those in Alzheimer's disease reported by other authors, and suggest
that neurodegenerative diseases as well as metabolic stress enhance the
metallothionein expression in perivascular regions of brain cerebral cortex,
predominantly in astrocytes.
PMID- 17031523
TI - Coxsackievirus and adenovirus receptor expression in non-malignant lung tissues
and clinical lung cancers.
AB - Adenoviral vector mediated gene delivery has been applied in clinical trials and
mechanistic studies to explore new treatment approaches for lung cancers. The
expression of coxsackievirus adenovirus receptor (CAR), the primary receptor for
the most commonly used adenovirus serotype 5 (Ad5)-based vectors, predominantly
determines the permissiveness of lung cancer cells. CAR expression is also
suggested to modulate tumor cell proliferation capacity. Here, we studied CAR
expression in archival lung cancer specimens by using well-characterized CAR 72
antibodies. High levels of CAR expression were observed in most of the 32 cases
of squamous cell carcinoma lung cancers and in all the five cases of small cell
lung cancers investigated. In contrast, high levels of CAR expression were
detected only in 6 of 22 adenocarcinoma lung cancers. The relative levels of CAR
expression did not correlate with the pathologic grade in lung cancers, and was
thus inconsistent with a role of modulating cancer cell proliferation. Of note,
CAR expression was not detected in non-malignant alveolar cells. Our data suggest
a preferred utility of Ad5 vector mediated gene delivery to squamous cell
carcinoma lung cancers, small cell lung cancers, but not to the majority of
adenocarcinoma lung cancers.
PMID- 17031524
TI - NMR assignment of the C-terminal domain of Ole e 9, a major allergen from the
olive tree pollen.
PMID- 17031525
TI - 1H, 13C and 15N resonance assignments of the VAP-A: OSBP complex.
PMID- 17031526
TI - Resonance assignments of a CoA binding protein from Klebsiella pneumoniae.
PMID- 17031527
TI - 1H, 13C and 15N resonance assignments of the catalytic domain of the goldfish
RICH protein.
PMID- 17031528
TI - A nomenclature and data model to describe NMR experiments.
AB - Despite ongoing efforts in organising NMR information, there is no consistent and
well-described generic standard for naming NMR experiments. The main reason for
the absence of a universal naming system is that the information content of the
coherence pathways is difficult to describe in full detail. We propose a system
that describes the common and generic elements of the coherence pathways produced
by pulse sequences. The system itself is formalised by an 'NMR experiment
protocol' model, which is described in the Universal Modelling Language (UML) as
part of the CCPN data model. Furthermore, normalized experiment names can be
derived from this proposed model. We hope this article will stimulate discussion
to organise the wealth of NMR experiments, and that by bringing this discussion
into the public domain we can improve and expand our proposed system to include
as much information and as many NMR experiments as possible.
PMID- 17031529
TI - Random sampling of evolution time space and Fourier transform processing.
AB - Application of Fourier Transform for processing 3D NMR spectra with random
sampling of evolution time space is presented. The 2D FT is calculated for pairs
of frequencies, instead of conventional sequence of one-dimensional transforms.
Signal to noise ratios and linewidths for different random distributions were
investigated by simulations and experiments. The experimental examples include 3D
HNCA, HNCACB and (15)N-edited NOESY-HSQC spectra of (13)C (15)N labeled ubiquitin
sample. Obtained results revealed general applicability of proposed method and
the significant improvement of resolution in comparison with conventional spectra
recorded in the same time.
PMID- 17031530
TI - Spectral editing: selection of methyl groups in multidimensional solid-state
magic-angle spinning NMR.
AB - A simple spectroscopic filtering technique is presented that may aid the
assignment of (13)C and (15)N resonances of methyl-containing amino-acids in
solid-state magic-angle spinning (MAS) NMR. A filtering block that selects methyl
resonances is introduced in two-dimensional (2D) (13)C-homonuclear and (15)N
(13)C heteronuclear correlation experiments. The 2D (13)C-(13)C correlation
spectra are recorded with the methyl filter implemented prior to a (13)C-(13)C
mixing step. It is shown that these methyl-filtered (13)C-homonuclear correlation
spectra are instrumental in the assignment of C(delta) resonances of leucines by
suppression of C(gamma)-C(delta) cross peaks. Further, a methyl filter is
implemented prior to a (15)N-(13)C transferred-echo double resonance (TEDOR)
exchange scheme to obtain 2D (15)N-(13)C heteronuclear correlation spectra. These
experiments provide correlations between methyl groups and backbone amides. Some
of the observed sequential (15)N-(13)C correlations form the basis for initial
sequence-specific assignments of backbone signals of the outer-membrane protein
G.
PMID- 17031531
TI - In-cell NMR spectroscopy of proteins inside Xenopus laevis oocytes.
AB - In-cell NMR is an application of solution NMR that enables the investigation of
protein conformations inside living cells. We have measured in-cell NMR spectra
in oocytes from the African clawed frog Xenopus laevis. (15)N-labeled ubiquitin,
its derivatives and calmodulin were injected into Xenopus oocytes and two
dimensional (1)H-(15)N correlation spectra of the proteins were obtained. While
the spectrum of wild-type ubiquitin in oocytes had rather fewer cross-peaks
compared to its in vitro spectrum, ubiquitin derivatives that are presumably
unable to bind to ubiquitin-interacting proteins gave a markedly larger number of
cross-peaks. This observation suggests that protein-protein interactions between
ubiquitin and ubiquitin-interacting proteins may cause NMR signal broadening, and
hence spoil the quality of the in-cell HSQC spectra. In addition, we observed the
maturation of ubiquitin precursor derivative in living oocytes using the in-cell
NMR technique. This process was partly inhibited by pre-addition of ubiquitin
aldehyde, a specific inhibitor for ubiquitin C-terminal hydrolase (UCH). Our work
demonstrates the potential usefulness of in-cell NMR with Xenopus oocytes for the
investigation of protein conformations and functions under intracellular
environmental conditions.
PMID- 17031532
TI - Interrogating the druggable genome with structural informatics.
AB - Structural genomics projects are producing protein structure data at an
unprecedented rate. In this paper, we present the Target Informatics Platform
(TIP), a novel structural informatics approach for amplifying the rapidly
expanding body of experimental protein structure information to enhance the
discovery and optimization of small molecule protein modulators on a genomic
scale. In TIP, existing experimental structure information is augmented using a
homology modeling approach, and binding sites across multiple target families are
compared using a clique detection algorithm. We report here a detailed analysis
of the structural coverage for the set of druggable human targets, highlighting
drug target families where the level of structural knowledge is currently quite
high, as well as those areas where structural knowledge is sparse. Furthermore,
we demonstrate the utility of TIP's intra- and inter-family binding site
similarity analysis using a series of retrospective case studies. Our analysis
underscores the utility of a structural informatics infrastructure for extracting
drug discovery-relevant information from structural data, aiding researchers in
the identification of lead discovery and optimization opportunities as well as
potential "off-target" liabilities.
PMID- 17031533
TI - Cheminformatics analysis and learning in a data pipelining environment.
AB - Workflow technology is being increasingly applied in discovery information to
organize and analyze data. SciTegic's Pipeline Pilot is a chemically intelligent
implementation of a workflow technology known as data pipelining. It allows
scientists to construct and execute workflows using components that encapsulate
many cheminformatics based algorithms. In this paper we review SciTegic's
methodology for molecular fingerprints, molecular similarity, molecular
clustering, maximal common subgraph search and Bayesian learning. Case studies
are described showing the application of these methods to the analysis of
discovery data such as chemical series and high throughput screening results. The
paper demonstrates that the methods are well suited to a wide variety of tasks
such as building and applying predictive models of screening data, identifying
molecules for lead optimization and the organization of molecules into families
with structural commonality.
PMID- 17031534
TI - SVM approach for predicting LogP.
AB - The logarithm of the partition coefficient between n-octanol and water (logP) is
an important parameter for drug discovery. Based upon the comparison of several
prediction logP models, i.e. Support Vector Machines (SVM), Partial Least Squares
(PLS) and Multiple Linear Regression (MLR), the authors reported SVM model is the
best one in this paper.
PMID- 17031535
TI - Reverse fingerprinting, similarity searching by group fusion and fingerprint bit
importance.
AB - Recent research has shown that using data fusion rules in fingerprint-based
similarity searching can improve results over traditional searches. Group fusion
scores, which use multiple reference compounds, have in particular been shown to
be quite effective in increasing enrichment rates over single reference structure
based searches. In this paper, the effectiveness of using data fusion with
multiple reference compounds to increase similarity search recall rates was
investigated using 44 biological targets and four different 2D fingerprinting
systems, including a new 2D typed triangle fingerprinting system introduced here.
Scaffold-hopping abilities using data fusion rules were investigated using eight
(8) different classes of scaffolds active against cGMP phosphodiesterase isoform
5 (PDE5). An approach to using the reference group for ranking and visualizing
important fingerprints bits, or reverse fingerprinting, was presented, and used
to score and visualize important pharmacophore features within sample active
molecules. Finally, similarity statistics within the reference groups were
investigated and compared to recall rates.
PMID- 17031536
TI - JEDA: Joint entropy diversity analysis. An information-theoretic method for
choosing diverse and representative subsets from combinatorial libraries.
AB - The joint entropy-based diversity analysis (JEDA) program is a new method of
selecting representative subsets of compounds from combinatorial libraries.
Similar to other cell-based diversity analyses, a set of chemical descriptors is
used to partition the chemical space of a library of compounds; however, unlike
other metrics for choosing a compound from each partition, a Shannon-entropy
based scoring function implemented in a probabilistic search algorithm determines
a representative subset of compounds. This approach enables the selection of
compounds that are not only diverse but that also represent the densities of
chemical space occupied by the original chemical library. Additionally, JEDA
permits the user to define the size of the subset that the chemist wishes to
create so that restrictions on time and chemical reagents can be considered.
Subsets created from a chemical library by JEDA are compared to subsets obtained
using other partition-based diversity analyses, namely principal components
analysis and median partitioning, on a combinatorial library derived from the
Comprehensive Medical Chemistry Dataset.
PMID- 17031537
TI - Differences in hepatotoxicity and gene expression profiles by anti-diabetic PPAR
gamma agonists on rat primary hepatocytes and human HepG2 cells.
AB - Agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) are a
new class of oral drugs designed to treat insulin-resistant diabetes (i.e., type
2 diabetes). However, troglitazone, the first compound in the class approved by
the US Food and Drug Administration (FDA) in 1997 was found to be hepatotoxic and
was withdrawn from the market after reports of severe liver failure. The
mechanism of PPAR gamma agonist-induced hepatotoxicity remains unknown. In this
study, we examined the hepatotoxic effects of five PPAR gamma agonists
(ciglitazone, pioglitazone, rosiglitazone, troglitazone, and JTT-501) on rat
primary hepatocytes and human HepG2 cells. We also compared the gene expression
profiles of rat primary hepatocytes after exposure to PPAR gamma agonists by
using the Rat Genome Survey Microarray system from Applied Biosystems in order to
understand the mechanisms of hepatotoxicities induced by PPARgamma agonists.
Consistent with the hepatotoxicity data, our results demonstrate that the gene
expression profiles affected by troglitazone and ciglitazone can be clearly
distinguished from those by pioglitazone and rosiglitazone. Genes that are
differentially expressed between the more toxic troglitazone/ciglitazone group
and the less toxic rosiglitazone/pioglitazone group are involved in necrotic,
apoptotic, and cell proliferative pathways. The five compounds were also
clustered based on a set of molecular descriptors. The clustering based on
chemical structural information is in good agreement with the clustering of
compounds based on cytotoxicity or gene expression data, indicating a strong
relationship between chemical structure and biological endpoints. Our work
suggests that microarray analysis together with toxicological observations can be
used to rank drugs for hepatotoxicity and to evaluate the safety of new
compounds.
PMID- 17031538
TI - Application of linear discriminant analysis in the virtual screening of
antichagasic drugs through trypanothione reductase inhibition.
AB - We have performed virtual screening to identify new lead trypanothione reductase
inhibitor (TRI) compounds, enzyme present in Tripanozoma cruzi, the agent
responsible of Chagas disease. From a training set of 58 compounds, linear
discriminant analysis (LDA) was performed using 2D and 3D descriptors as
discriminating variables in order to find out which function of descriptors
characterizes the active TRI. The values of the statistical parameters F-
Snedecor and Wilk's lambda for the discriminant function (DF) showed good
statistical significance, as long as the rate of success in the prediction for
both the training and the test set: 91.38% and 88.63%, in that order. Internal
validation through the Leave--Group--Out methodology was performed with good
results, assuring the stability of the DF. Afterwards, the DF was applied in
virtual screening of 422,367 compounds. The optimum range of values of octanol-
water partition coefficient for a compound to develop trypanothione reductase
inhibition was applied as a second filtering criteria. 739 structurally
heterogeneous drugs of the virtual library were selected as promissory TRI.
PMID- 17031539
TI - Leadlikeness and structural diversity of synthetic screening libraries.
AB - High program failure rates in the pharmaceutical industry have prompted the
development of predictive software that can profile compound libraries as being
'druglike' (resembling existing drugs) and/or 'leadlike' (possessing the
structural and physicochemical profile of a quality lead). In recent years, these
two notions prompted pharmaceutical companies to clean up their corporate
libraries of screening compounds. In order to maintain and expand the size and
diversity of these corporate libraries, pharmaceutical companies still continue
to add compounds to these, mainly by the acquisition of screening libraries. In
this paper, we have analyzed 45 commercially available libraries, offered by
suppliers of screening chemistry, for leadlikeness and diversity of the offered
structures. To this end we have used a set of structural and physicochemical
filters for leadlikeness that was developed in-house. These 45 supplier libraries
contained a total of 5.3 million structures, of which 49% (2,592,778 structures)
turned out to be unique, and only 12% (677,328 structures) were found to be both
unique and leadlike. A diversity analysis revealed that big differences exist
between the various offered libraries.
PMID- 17031540
TI - Managing, profiling and analyzing a library of 2.6 million compounds gathered
from 32 chemical providers.
AB - The data for 3.8 million compounds from structural databases of 32 providers were
gathered and stored in a single chemical database. Duplicates are removed using
the IUPAC International Chemical Identifier. After this, 2.6 million compounds
remain. Each database and the final one were studied in term of uniqueness,
diversity, frameworks, 'drug-like' and 'lead-like' properties. This study also
shows that there are more than 87 000 frameworks in the database. It contains 2.1
million 'drug-like' molecules among which, more than one million are 'lead-like'.
This study has been carried out using 'ScreeningAssistant', a software dedicated
to chemical databases management and screening sets generation. Compounds are
stored in a MySQL database and all the operations on this database are carried
out by Java code. The druglikeness and leadlikeness are estimated with 'in-house'
scores using functions to estimate convenience to properties; unicity using the
InChI code and diversity using molecular frameworks and fingerprints. The
software has been conceived in order to facilitate the update of the database.
'ScreeningAssistant' is freely available under the GPL license.
PMID- 17031541
TI - Microwave assisted oxidation of some aromatics by hydrogen peroxide at supported
tungsten catalyst.
AB - The oxidation of some arenes with the alkyl side groups by means of hydrogen
peroxide is been presented. As the activator of hydrogen peroxide tungstoboric
acid was chosen. The catalyst was examined under both homogeneous and
heterogeneous conditions. The reactions under conventional conditions were
compared with the microwave assisted reactions.
PMID- 17031542
TI - A novel workflow for the inverse QSPR problem using multiobjective optimization.
AB - A workflow for the inverse quantitative structure-property relationship (QSPR)
problem is reported in this paper for the de novo design of novel chemical
entities (NCE) in silico through the application of existing QSPR models to
calculate multiple objectives, including prediction confidence measures, to be
optimized during the de novo design process. Two physical property datasets are
applied as case studies of the inverse QSPR workflow (IQW): mean molecular
polarizability and aqueous solubility. The case studies demonstrate the
optimization of molecular structures to within a property range of interest; the
optimized structures are then validated against QSPR models that are generated
from sets of alternative descriptors to those used in the IQW. The paper
concludes with a discussion of the results from the case studies.
PMID- 17031543
TI - Ascorbate peroxidase-thioredoxin interaction.
AB - Proteomics data have suggested ascorbate peroxidase (APX) to be a potential
thioredoxin-interacting protein. Using recombinant enzymes, we observed that
incubation of pea cytosolic APX with reduced poplar thioredoxins h drastically
inactivated the peroxidase. A similar inactivation is induced by reduced
glutathione and dithiothreitol, whereas diamide and oxidized glutathione have no
effect. Oxygen consumption measurements, modifications of the APX visible
spectrum and protection by hydrogen peroxide scavenging enzymes suggest that APX
oxidizes thiols leading to the generation of thiyl radicals. These radicals can
in turn react with thiyl anions to produce the disulfide radical anions, which
are responsible for oxygen reduction and subsequent hydrogen peroxide production.
The APX inactivation is not due solely to hydrogen peroxide since fluorimetry
indicates that the environment of the APX tryptophan residues is dramatically
modified only in the presence of thiol groups. The physiological implications of
this interaction are discussed.
PMID- 17031544
TI - Thioredoxin-dependent regulation of photosynthetic glyceraldehyde-3-phosphate
dehydrogenase: autonomous vs. CP12-dependent mechanisms.
AB - Regulation of the Calvin-Benson cycle under varying light/dark conditions is a
common property of oxygenic photosynthetic organisms and photosynthetic
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the targets of this
complex regulatory system. In cyanobacteria and most algae, photosynthetic GAPDH
is a homotetramer of GapA subunits which do not contain regulatory domains. In
these organisms, dark-inhibition of the Calvin-Benson cycle involves the
formation of a kinetically inhibited supramolecular complex between GAPDH, the
regulatory peptide CP12 and phosphoribulokinase. Conditions prevailing in the
dark, i.e. oxidation of thioredoxins and low NADP(H)/NAD(H) ratio promote
aggregation. Although this regulatory system has been inherited in higher plants,
these phototrophs contain in addition a second type of GAPDH subunits (GapB)
resulting from the fusion of GapA with the C-terminal half of CP12.
Heterotetrameric A(2)B(2)-GAPDH constitutes the major photosynthetic GAPDH
isoform of higher plants chloroplasts and coexists with CP12 and A(4)-GAPDH. GapB
subunits of A(2)B(2)-GAPDH have inherited from CP12 a regulatory domain (CTE for
C-terminal extension) which makes the enzyme sensitive to thioredoxins and
pyridine nucleotides, resembling the GAPDH/CP12/PRK system. The two systems are
similar in other respects: oxidizing conditions and low NADP(H)/NAD(H) ratios
promote aggregation of A(2)B(2)-GAPDH into strongly inactivated A(8)B(8)-GAPDH
hexadecamers, and both CP12 and CTE specifically affect the NADPH-dependent
activity of GAPDH. The alternative, lower activity with NADH is always
unaffected. Based on the crystal structure of spinach A(4)-GAPDH and the analysis
of site-specific mutants, a model of the autonomous (CP12-independent) regulatory
mechanism of A(2)B(2)-GAPDH is proposed. Both CP12 and CTE seem to regulate
different photosynthetic GAPDH isoforms according to a common and ancient
molecular mechanism.
PMID- 17031545
TI - Plant methionine sulfoxide reductase A and B multigenic families.
AB - Methionine oxidation to methionine sulfoxide (MetSo), which results in
modification of activity and conformation for many proteins, is reversed by an
enzyme present in most organisms and termed as methionine sulfoxide reductase
(MSR). On the basis of substrate stereospecificity, two types of MSR, A and B,
that do not share any sequence similarity, have been identified. In the present
review, we first compare the multigenic MSR families in the three plant species
for which the genome is fully sequenced: Arabidopsis thaliana, Oryza sativa, and
Populus trichocarpa. The MSR gene content is larger in A. thaliana (five MSRAs
and nine MSRBs) compared to P. trichocarpa (five MSRAs and four MSRBs) and O.
sativa (four MSRAs and three MSRBs). A complete classification based on gene
structure, sequence identity, position of conserved reactive cysteines and
predicted subcellular localization is proposed. On the basis of in silico and
experimental data originating mainly from Arabidopsis, we report that some MSR
genes display organ-specific expression patterns and that those encoding
plastidic MSRs are highly expressed in photosynthetic organs. We also show that
the expression of numerous MSR genes is enhanced by environmental conditions
known to generate oxidative stress. Thioredoxins (TRXs) constitute very likely
physiological electron donors to plant MSR proteins for the catalysis of MetSO
reduction, but the specificity between the numerous TRXs and methionine sulfoxide
reductases (MSRs) present in plants remains to be investigated. The essential
role of plant MSRs in protection against oxidative damage has been recently
demonstrated on transgenic Arabidopsis plants modified in the content of
cytosolic or plastidic MSRA.
PMID- 17031546
TI - Evolution of redoxin genes in the green lineage.
AB - The availability of the Arabidopsis genome revealed the complexity of the gene
families implicated in dithiol disulfide exchanges. Most non-green organisms
present less dithiol oxidoreductase genes. The availability of the almost
complete genome sequence of rice now allows a systematic search for thioredoxins,
glutaredoxins and their reducers. This shows that all redoxin families previously
defined for Arabidopsis have members in the rice genome and that all the deduced
rice redoxins fall within these families. This establishes that the redoxin
classification applies both to dicots and monocots. Nevertheless, within each
redoxin type the number of members is not the same in these two higher plants and
it is not always possible to define orthologues between rice and Arabidopsis. The
sequencing of two unicellular algae (Chlamydomonas and Ostreococcus) genomes are
almost finished. This allowed us to follow the origin of the different gene
families in the green lineage. It appears that most thioredoxin and glutaredoxin
types, their chloroplastic, mitochondrial and cytosolic reducers are always
present in these unicellular organisms. Nevertheless, striking differences appear
in comparison to higher plant redoxins. Some thioredoxin types are not present in
these algal genomes including thioredoxins o, clot and glutaredoxins CCxC.
Numerous redoxins, including the cytosolic thioredoxins, do not fit with the
corresponding higher plant classification. In addition both algae present a NADPH
dependent thioredoxin reductase with a selenocysteine which is highly similar to
the animal thioredoxin reductases, a type of thioredoxin reductase not present in
higher plants.
PMID- 17031549
TI - MitoK(ATP)-dependent changes in mitochondrial volume and in complex II activity
during ischemic and pharmacological preconditioning of Langendorff-perfused rat
heart.
AB - It has been proposed that activation of the mitochondrial ATP-sensitive potassium
channel (mitoK(ATP)) is part of signaling pathways triggering the
cardioprotection afforded by ischemic preconditioning of the heart. This work was
to analyze the mitochondrial function profile of Langendorff-perfused rat hearts
during the different phases of various ischemia-reperfusion protocols.
Specifically, skinned fibers of ischemic preconditioned hearts exhibit a decline
in the succinate-supported respiration and complex II activity during ischemia,
followed by a recovery during reperfusion. Meanwhile, the apparent affinity of
respiration for ADP (which reflects the matrix volume expansion) is increased
during preconditioning stimulus and, to a larger extent, during prolonged
ischemia. This evolution pattern is mimicked by diazoxide and abolished by 5
hydroxydecanoate. It is concluded that opening the mitoK(ATP) channel mediates
the preservation of mitochondrial structure-function via a mitochondrial matrix
shrinkage and a reversible inactivation of complex II during prolonged ischemic
insult.
PMID- 17031550
TI - Electrical stimulation of the energy metabolism in yeast cells using a planar Ti
Au-electrode interface.
AB - We report on the influence of dielectric pulse injection on the energy metabolism
of yeast cells with a planar interdigitated electrode interface. The energy
metabolism was measured via NADH fluorescence. The application of dielectric
pulses results in a distinct decrease of the fluorescence, indicating a response
of the energy metabolism of the yeast cells. The reduction of the NADH signal
significantly depends on the pulse parameters, i.e., amplitude and width.
Furthermore, the interface is used to detect electrical changes in the cell
electrolyte system, arising from glucose-induced oscillations in yeast cells and
yeast extract, by dielectric spectroscopy at 10 kHz. These dielectric
investigations revealed a beta(1)-dispersion for the system electrolyte/yeast
cells as well as for the system electrolyte/yeast extract. In agreement with
control measurements we obtained a glycolytic period of 45 s for yeast cells and
of 11 min for yeast extract.
PMID- 17031551
TI - Painful languages of the body: experiences of headache among women in two
Peruvian communities.
AB - This exploratory study focuses on the understandings of and experiences with
headache in two settings in Peru: the Quechua-speaking district of Ayacucho, in
southern Peru, and a poor urban district of Lima Metropolitana. More
specifically, it explores the personal and collective meanings constructed around
women's headache experiences. Structured and open-ended interviews were
administered to patients suffering headache to elicit interpretations of headache
episodes. An analysis of the collected narratives suggests that headache is often
comprehended in a polysemic framework, where meanings ascribed in bodily,
emotional, family, and social terms articulate individual and shared notions of
suffering within larger contexts of social dislocation. Often woven into
experiences of solitude, headache accounts are lived and told in dynamic temporal
spaces, and narrate dissolution of family ties and tensions associated with
women's roles. The results underscore the significance of patients' subjective
interpretations of painful experiences and underscore the connections between
bodily and emotional pain and distress experienced at family, community, and
larger social levels.
PMID- 17031552
TI - Monitoring the effects of BCNU chemotherapy Wafers (Gliadel) in glioblastoma
multiforme with proton magnetic resonance spectroscopic imaging at 3.0 Tesla.
AB - Carmustine wafers (Gliadel Wafer) are implanted at resection in some patients
with high-grade gliomas. Studies suggest that proton magnetic resonance
spectroscopic imaging ((1)H MRSI) demonstrates early changes predictive of future
failure or response to systemic chemotherapy. This study explores (1)H MRSI as a
means to assess peri-tumoral tissue response post-resection and Gliadel((R))
implantation in patients with high-grade gliomas. Pilot (1)H MRSI data are
presented that demonstrate noninvasive, serial monitoring of metabolic changes at
the tumor site following Gliadel implantation. Three patients with newly
diagnosed glioblastoma multiforme (GBM) underwent MRI and (1)H MRSI at 3.0 Tesla
prior to resection and at 3-5 and > or =12 weeks post-operatively. Baseline MRS
spectra of tumor tissue from all patients were characterized by marked increases
of choline (CHO) and lactate (LAC), and a decrease of N-acetylaspartate (NAA),
typical of GBM compared with normal contra-lateral brain tissue. Post
operatively, spectra were analyzed from the resection cavity and peri-tumoral
regions and compared with normal tissue from the contra-lateral brain at
baseline. In 2 of 3 patients, peri-tumoral NAA/CRE increased and CHO/NAA
decreased compared to contra-lateral brain at 3-5 weeks compared with baseline
following Gliadel therapy and surgery but prior to radiotherapy. This study
indicates that (1)H MRSI has the ability to localize regions of heterogeneous
response following Gliadel treatment. Although data are limited, these results
suggest that metabolic indicators of outcome can be successfully monitored pre-
and post-surgical resection and Gliadel implantation with (1)H MRSI. Additional
study of patients receiving Gliadel Wafers using (1)H MRSI may serve to aid
clinicians in assessing tumor regression and gauging efficacy of this
chemotherapy treatment.
PMID- 17031553
TI - Phase II study of thalidomide and radiation in children with newly diagnosed
brain stem gliomas and glioblastoma multiforme.
AB - A phase II study was conducted to assess the efficacy of administering daily
thalidomide concomitantly with radiation and continuing for up to 1 year
following radiation in children with brain stem gliomas (BSG) or glioblastoma
multiforme (GBM). Secondary objectives were to obtain preliminary evidence of
biologic activity of thalidomide and to evaluate toxicities from chronic
administration of thalidomide in this population. Thirteen patients (2-14 years
old) with newly diagnosed BSG (12 patients) or GBM (one patient) were enrolled
between July 1999 and June 2000. All patients received focal radiotherapy to a
total dose of 5,580 cGy. Thalidomide was administered once daily beginning on the
first day of radiation and continued for 12 months or until the patient came off
study. The starting dose was 12 mg/kg (rounded down to the nearest 50 mg) and was
increased by 20% weekly, if tolerated, to 24 mg/kg or 1,000 mg (whichever was
lower). Advanced imaging techniques and urine and serum analysis for anti
angiogenic markers were performed in some patients in an attempt to correlate
changes with clinical effect of therapy. No patients completed the planned 12
months of thalidomide therapy and all have since died of disease progression. The
median duration of therapy was 5 months (range 2-11 months). Nine patients came
off study for progressive disease (PD), three patients due to toxicity and one
patient withdrew consent. Several patients on this study required more extended
courses of high dose steroids than would have been otherwise expected for this
population due to significant peritumoral edema and necrosis. No consistent
pattern emerged from the biologic correlative studies from 11 patients. However,
advanced imaging with techniques such as MR spectroscopy, MR perfusion and 18
fluorodeoxyglucose positron emission tomography (FDG-PET) were helpful in
distinguishing growing tumor from treatment effect and necrosis in some patients.
The median time to progression (TTP) was 5 months (range 2-11 months) and the
median time to death (TTD) was 9 months (range 5-17 months). In this small
patient sample adding thalidomide to radiation did not improve TTP or TTD from
historical controls, however, toxicity appeared to be increased.
PMID- 17031554
TI - Safety and efficacy of convection-enhanced delivery of ACNU, a hydrophilic
nitrosourea, in intracranial brain tumor models.
AB - Convection-enhanced delivery (CED) is a local infusion technique, which delivers
chemotherapeutic agents directly to the central nervous system, circumventing the
blood-brain barrier and reducing systemic side effects. CED distribution is
significantly increased if the infusate is hydrophilic. This study evaluated the
safety and efficacy of CED of nimustine hydrochloride: 3-[(4-amino-2-methyl-5
pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), a
hydrophilic nitrosourea, in rat 9 L: brain tumor models. The local neurotoxicity
of ACNU delivered via CED was examined in normal rat brains, and the maximum
tolerated dose (MTD) was estimated at 0.02 mg/rat. CED of ACNU at the MTD
produced significantly longer survival time than systemic administration (P <
0.05, log-rank test). Long-term survival (80 days) and eradication of the tumor
occurred only in the CED-treated rats. The tissue concentration of ACNU was
measured by high-performance liquid chromatography, which revealed that CED of
ACNU at the dose of 100-fold less total drug than intravenous injection carried
almost equivalent concentrations of ACNU into rat brain tissue. CED of
hydrophilic ACNU is a promising strategy for treating brain tumors.
PMID- 17031555
TI - Local intracerebral administration of O(6)-benzylguanine combined with systemic
chemotherapy with temozolomide of a patient suffering from a recurrent
glioblastoma.
AB - The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a major
determinant of methylating anticancer drug resistance. Inactivation of MGMT by
pseudosubstrate inhibitors, such as O(6)-benzylguanine (O(6)BG), sensitizes tumor
cells to O(6)-alkylating agents. However, systemic administration of O(6)BG
causes depletion of MGMT in all tissues of the body. Therefore, dose reduction of
O(6)-alkylating drugs administered together with O(6)BG is required in order to
avoid unwished toxic side effects. To attenuate the increased systemic toxicity
caused by MGMT inhibitors, local MGMT inactivation would be desirable. Here, we
report on intracerebral treatment with O(6)BG of a patient suffering from
glioblastoma. O(6)BG was administered weekly in the tumor cavity by means of an
Ommaya reservoir. This application was well tolerated. Concomitant treatment with
temozolomide (Temodal) was associated with transient tumor stabilization without
detectable side effects. Although evidence is still lacking that local O(6)BG
administration caused MGMT to be depleted in the residual tumor, the trial shows
that intracerebral treatment with O(6)BG is feasible. It might be a safe strategy
for improving glioma therapy by treatment with temozolomide (and presumably also
other O(6)-alkylating drugs) concomitant with O(6)BG without augmenting drug
induced systemic side effects.
PMID- 17031556
TI - Anaplastic ependymoma with cartilaginous and osseous metaplasia: report of a rare
case and review of literature.
AB - Gliomas with cartilaginous metaplasia are extremely uncommon and thought to be
due to metaplasia of the mesenchymal supportive elements. The tumors are located
in the midline, mostly fourth ventricle and rarely in the pons. The present paper
describes an unusual case of anaplastic ependymoma with cartilaginous and osseous
metaplasia in a young boy which was located in the suprasellar, interpeduncular
prepontine and left cerebello-pontine cistern. To the best of our knowledge, this
cartilaginous metaplasia in ependymomas has been reported only thrice.
PMID- 17031557
TI - Administration of temozolomide during and after radiotherapy for newly diagnosed
high-grade gliomas excluding glioblastoma multiforme.
AB - Primary brain high-grade gliomas, excluding glioblastoma are rare and
heterogeneous tumors, showing different characteristic mutations and a better
prognosis than glioblastomas. The addition of chemotherapy to the radiotherapy in
the newly diagnosed disease has not been established yet. We treated 9 patients
with newly diagnosed tumors with temozolomide at 75 mg/m2 for 7 days a week
during standard radiotherapy, followed by six cycles at 200 mg/m2 on days 1-5
every 28 days. Fluorescence in situ hybridization for the 1 p/19 q loss was
performed in seven out of the 9 patients. With a median follow-up of 15 months
(range, 8-50), eight patients are alive and one died from disease progression.
Four patients had disease progression at 7, 15, 14 and 13 months from the
diagnosis. The 1 p/19 q loss was found in 5 patients; three have no evidence of
disease, one had partial disease remission and one disease progression.
Toxicities included one discitis requiring treatment withdrawal and specific
antibiotic therapy, and one transient grade 3 psoriasiform reaction. Based on
this small series of patients, the addition of temozolomide to radiotherapy may
be recommended.
PMID- 17031558
TI - Survival and quality of life after hypofractionated stereotactic radiotherapy for
recurrent malignant glioma.
AB - PURPOSE: To prospectively evaluate efficacy, side effects and quality of life in
patients with recurrent malignant glioma after hypofractionated stereotactic
radiotherapy. METHODS AND MATERIALS: From 1/2003 to 8/2005, 15 patients with
recurrent malignant glioma were prospectively scheduled for hfSRT with 5 x 7 Gy
(90%-isodose). Median gross tumor volume and planning target volume were 5.75
(range, 0.77-21.94) and 22.4 (range, 4.22-86.79) cc, respectively. Irradiation
was performed with the dedicated stereotactic radiosurgery system Novalistrade
mark (BrainLAB, Heimstetten, Germany). RESULTS: Rates of remission, no change and
progressive disease were 27%, 33%, and 40%, respectively, after a median follow
up of 9 months. Progression-free survival rates at 6 and 12 months were 75% and
53% respectively. Quality of life, measured by the European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire scores could be
kept stable in two thirds of the patients for a median time of 9 months,
respectively. CONCLUSION: Hypofractionated stereotactic radiotherapy with 5 x 7
Gy of recurrent high grade glioma is an effective treatment that helps to
maintain quality of life for an acceptable period, comparable to the results
obtained with current chemotherapy schedules. Combined approaches of
radiotherapy, chemotherapy and other targeted therapies deserve further
inverstigation.
PMID- 17031559
TI - PLXDC1 (TEM7) is identified in a genome-wide expression screen of glioblastoma
endothelium.
AB - Glioblastomas are a highly aggressive brain tumor, with one of the highest rates
of new blood vessel formation. In this study we used a combined experimental and
bioinformatics strategy to determine which genes were highly expressed and
specific for glioblastoma endothelial cells (GBM-ECs), compared to gene
expression in normal tissue and endothelium. Starting from fresh glioblastomas,
several rounds of negative and positive selection were used to isolate GBM-ECs
and extract total RNA. Using Serial Analysis of Gene Expression (SAGE), 116,259
transcript tags (35,833 unique tags) were sequenced. From this expression
analysis, we found 87 tags that were not expressed in normal brain. Further
subtraction of normal endothelium, bone marrow, white blood cell and other normal
tissue transcripts resulted in just three gene transcripts, ANAPC10,
PLXDC1(TEM7), and CYP27B1, that are highly specific to GBM-ECs.
Immunohistochemistry with an antibody for PLXDC1 showed protein expression in GBM
microvasculature, but not in the normal brain endothelium tested. Our results
suggest that this study succeeded in identifying GBM-EC specific genes. The
entire gene expression profile for the GBM-ECs and other tissues used in this
study are available at SAGE Genie (http://cgap.nci.nih.gov/SAGE). Functionally,
the protein products of the three tags most specific to GBM-ECs have been
implicated in processes critical to endothelial cell proliferation and
differentiation, and are potential targets for anti-angiogenesis based therapy.
PMID- 17031560
TI - Resveratrol inhibits cell growth and induces apoptosis of rat C6 glioma cells.
AB - Resveratrol (Res) has been reported to inhibit tumor initiation, promotion, and
progression in a variety of cell culture systems depending on the specific cell
type and cellular environment. In the present study, we determined the effect of
Res on the cell growth and apoptosis of rat glioma C6 cell line as well as mouse
fibroblast 3T3 cell line, in vitro. Concurrently, we investigated whether caspase
3 is involved in the Res-induced apoptosis of rat glioma cells. Exposure to Res
exhibits a significant anti-proliferative effect and induces an increase in the
population of apoptotic cells on C6 cells in a concentration- and time-dependent
manner, but not for normal 3T3 fibroblast cells, as measured by methyl thiazolyl
tetrazolium assay and flow cytometer. Distinguished increase of C6 cells in S
phase is observed after the treatment of Res as compared to insignificant change
in cell cycle distribution of 3T3 cells. TdT-mediated dUTP nick end labeling
fluorescence staining, HE staining, and scanning electron microscope revealed
abnormal morphology and ultrastructure in C6 cells treated with Res. Our data
showed that Res can increase the expression and induced the activation of caspase
3 in rat glioma C6 cells. These results suggest that Res has significant
apoptosis-inducing effect on C6 glioma cells other than normal fibroblast 3T3
cells in vitro and caspase-3 may act as a potential mediator in the process.
PMID- 17031561
TI - A North American brain tumor consortium (NABTC 99-04) phase II trial of
temozolomide plus thalidomide for recurrent glioblastoma multiforme.
AB - BACKGROUND: Laboratory and clinical data suggest that the anti-angiogenic agent,
thalidomide, if combined with cytotoxic agents, may be effective against
recurrent glioblastoma multiforme (GBM). OBJECTIVES: To determine 6-month
progression-free survival (6PFS) and toxicity of temozolomide plus thalidomide in
adults with recurrent GBM. PATIENTS AND METHODS: Eligible patients had recurrent
GBM after surgery, radiotherapy, and/or adjuvant chemotherapy. Temozolomide was
given at 150-200 mg/m(2)/day on days 1-5 of each 28-day cycle. Thalidomide was
given orally at 400 mg at bedtime (days 1-28) and increased to 1,200 mg as
tolerated. Patients were evaluated with magnetic resonance imaging scans every 56
days. The study was designed to detect an increase of the historical 6PFS for GBM
from 10 to 30%. RESULTS: Forty-four patients were enrolled, 43 were evaluable for
efficacy and safety. The study population included 15 women, 29 men; median age
was 53 years (range 32-84); median Karnofsky performance status was 80% (range 60
100%). Thirty-six (82%) patients were chemotherapy-naive. There were 57 reports
of toxicity of grade 3 or greater. Non-fatal grade 3-4 granulocytopenia occurred
in 15 patients (34%). The objective response rate was 7%. The estimated
probability of being progression-free at 6 months with this therapy is 24% [95%
confidence interval (C.I.) 12-38%]. The median time to progression is 15 weeks
(95% C.I. 10-20 weeks). There was no observed correlation between serum levels of
vascular endothelial growth factor, basic fibroblast growth factor, and IL-8 and
the 6PFS outcome. CONCLUSION: This drug combination was reasonably safe, but with
little indication of improvement compared to temozolomide alone.
PMID- 17031562
TI - EGF genetic polymorphism is associated with clinical features but not malignant
phenotype in neurofibromatosis type 1 patients.
AB - Neurofibromatosis type 1 (NF1) is characterized by a wide variation in clinical
presentation and in some cases progression to malignant tumor. Epidermal growth
factor (EGF) is an important mitogen for Schwann cells and is involved in the
development of malignant tumors in NF1 patients. We hypothesized that EGF +61 G/A
functional polymorphism, which represents constitutional all-life exposure to
higher EGF expression and circulating levels, may predispose for precocious and
more aggressive manifestations of disease. We found that clinical findings of
intestinal polyps are significantly more frequent in patients with G homozygous
genotype (P = 0.023). Those carriers of GG genotype have earlier onset of cafe-au
lait spots and Lisch nodules appearance (P = 0.030 and P = 0.017, respectively).
Nevertheless, the EGF overexpressing genotype-GG, is not associated with higher
risk for malignant progression or severity of disease. EGF polymorphism may play
a role in the earlier onset of NF1 pigment cell-related manifestations and in
intestinal polyps' development. Further studies in larger samples should confirm
the absence of risk for having higher severity grade or malignant phenotype in
NF1 patients.
PMID- 17031563
TI - A case report and review of the literature.
AB - Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare central nervous
system neoplasm in which gliomatous tissue is diffusely identified in the
subarachnoid space with no evidence of a primary intraparenchymal tumor. A 52
year-old man presented low back pain followed by sudden unconsciousness and had
also cognitive dysfunction and meningeal sign. Examinations of cerebrospinal
fluid (CSF) did not show malignant cells but increased protein and pleocytosis.
Magnetic resonance (MR) imaging demonstrated diffuse leptomeningeal enhancement
without any source of intraparenchymal lesion. Fluid-attenuated inversion
recovery (FLAIR) also demonstrated individual diffuse high intensity area in the
subarachnoid space. A biopsy disclosed wide spreading of anaplastic glial cells
within the leptomeninges. He died 3 months later because of disease progression
despite both radiotherapy and chemotherapy. Post-mortem examination identified
PDLG and several neuropathological features of glioblastoma as well. Reviewing
previous cases of PDLG instructs that this entity is rare, resembles meningitis
in clinical pictures, usually occurs in a relatively younger population and has
more progressive clinical course than the ordinary form of malignant gliomas.
PMID- 17031564
TI - The role of citrullinated proteins suggests a novel mechanism in the pathogenesis
of multiple sclerosis.
AB - The pathogenesis of MS is unknown. In our studies, we have demonstrated an
important role for citrullinated myelin basic protein (MBP). The accompanying
loss of positive charge compromises the ability of MBP to interact with the lipid
bilayer. The conversion of arginine to citrulline in brain is carried out by an
enzyme peptidyl arginine deiminase (PAD) 2. The amount of PAD 2 in brain was
increased in MS normal-appearing white matter. The mechanism responsible for this
increase involved hypomethylation of the promoter region in the PAD 2 gene in MS,
but no change (compared to normal) was found in thymus tissue DNA from the same
MS patients. In addition, no change was observed in other neurological diseases,
including Alzheimer's, Parkinson's, and Huntington's. We propose that
citrullinated MBP, resulting from elevated levels of PAD 2 represents an
important biochemical pathway in the pathogenesis of MS.
PMID- 17031565
TI - Dopamine reduction of GABA currents in striatal medium-sized spiny neurons is
mediated principally by the D(1) receptor subtype.
AB - Dopamine modulates voltage- and ligand-gated currents in striatal medium-sized
neurons (MSNs) through the activation of D1- and D2-like family receptors.
GABA(A) receptor-mediated currents are reduced by D1 receptor agonists, but the
relative contribution of D(1) or D(5 )receptors in this attenuation has been
elusive due to the lack of selective pharmacological agents. Here we examined
GABA(A) receptor-mediated currents and the effects of D1 agonists on MSNs from
wildtype and D(1) or D(5 )receptor knockout (KO) mice. Immunohistochemical and
single-cell RT-PCR studies demonstrated a lack of compensatory effects after
genetic deletion of D(1) or D(5) receptors. However, the expression of GABA(A
)receptor alpha1 subunits was reduced in D(5) KO mice. At the functional level,
whole-cell patch clamp recordings in dissociated MSNs showed that GABA peak
current amplitudes were smaller in cells from D(5) KO mice indicating that lack
of this receptor subtype directly affected GABA(A)-mediated currents. In striatal
slices, addition of a D1 agonist reduced GABA currents significantly more in D(5)
KO compared to D(1) KO mice. We conclude that D(1) receptors are the main D1-like
receptor subtype involved in the modulation of GABA currents and that D(5)
receptors contribute to the normal expression of these currents in the striatum.
PMID- 17031567
TI - Assessment of respondent driven sampling for recruiting female sex workers in two
Vietnamese cities: reaching the unseen sex worker.
AB - Respondent driven sampling (RDS) is a relatively new method to sample hard-to
reach populations. Until this study, female sex workers (FSWs) in Vietnam were
sampled using a variety of methods, including time location sampling (TLS), which
may not access the more hidden types of FSWs. This paper presents an analysis
from an HIV biological and behavioral surveillance survey to assess the
feasibility and effectiveness of RDS to sample FSWs, to determine if RDS can
reach otherwise inaccessible FSWs in Vietnam and to compare RDS findings of HIV
risk factors with a theoretical TLS. Through face-to-face interviews with FSWs in
Ho Chi Minh City (HCMC) and Hai Phong (HP), data were collected about the venues
where they most often solicit their clients. These data were used to create three
variables to assess whether FSWs solicit their clients in locations that are
visible, semi-visible and non-visible. For this analysis, the visible group
simulates a sample captured using TLS. Survey results in HIV prevalence and
related risk factors and service utilization, adjusted for sampling methodology,
were compared across each of the three FSW visibility groups to assess potential
bias in TLS relative to RDS. The number of self-reported visible FSWs (HCMC:
n=311; HP: n=162) was much larger than those of the semi-visible (HCMC: n=65; HP:
n=43) and non-visible (HCMC: n=37; HP: n=10) FSWs in HCMC and HP. Non-visible
FSWs in both cities were just as likely as visible and semi-visible FSWs to be
HIV positive (HCMC: visible 14.5%, semi-visible 13.8%, non-visible 13.5%, p value
= 0.982; HP: visible 35.2%, semi-visible 30.2%, non-visible 30.0%, p value =
0.801), to practice behaviors that put them at risk for contracting and
transmitting HIV (injecting drug use-HCMC: visible 13.8%, semi-visible 12.3%, non
visible 5.4%, p value = 0.347; HP: visible 38.9%, semi-visible 23.3%, non-visible
30.0%, p value = 0.378, to have no condom use in the past month -HCMC only:
visible 52.7%, semi-visible 63.1%, non-visible 48.6%, p value = 0.249) and to
have symptoms of a sexually transmitted infection (STI) in the past year (HCMC:
visible 16.1%, semi-visible 12.3%, non-visible 16.2%, p value = 0.742; HP:
visible 13.6%, semi-visible 18.6%, non-visible 20.0%, p value = 0.640). There was
a difference found among the visible, semi-visible and non-visible groups in HP
for no past month condom use (visible 53.1%, semi-visible 79.1%, non-visible
60.0%, p value = 0.009). This study found that RDS was successful at recruiting
hidden types of FSWs in Vietnam. Past reports of FSWs in Vietnam have assessed
the more visible FSWs as being the most vulnerable and at risk for HIV. Although
the number of visible FSWs is much higher than those of the semi and non-visible
groups, this study found that the non-visible FSWs are very vulnerable to HIV
infection. If prevention programs are targeting and responding to those who are
most likely to be assessed (e.g., more visible types of FSWs) then this analysis
indicates that a significant proportion of the FSW population at risk for HIV may
not be receiving optimal HIV information and services.
PMID- 17031566
TI - White matter rafting--membrane microdomains in myelin.
AB - The myelin membrane comprises a plethora of regions that are compositionally,
ultrastructurally, and functionally distinct. Biochemical dissection of
oligodendrocytes, Schwann cells, and central and peripheral nervous system myelin
by means such as cold-detergent extraction and differential fractionation has led
to the identification of a variety of detergent-resistant membrane assemblies,
some of which represent putative signalling platforms. We review here the
different microdomains that have hitherto been identified in the myelin membrane,
particularly lipid rafts, caveolae, and cellular junctions such as the tight
junctions that are found in the radial component of the CNS myelin sheath.
PMID- 17031569
TI - Flow cytometry sorting protocol of Bacillus spore using ultraviolet laser and
autofluorescence as main sorting criterion.
AB - The ultraviolet (UV) Fluorescent Aerodynamic Particle Sizer (FLAPS), a flow
cytometer-like apparatus was developed by the Canadian Department of National
Defence for real-time detection of autofluorescence of biological aerosol
particles such as bacterial spores. The direct relation between autofluorescence
intensity and viability has recently been reported and viable spore are more
autofluorescent in UV (Laflamme, Frontiers in Bioscience). The goal of this
manuscript is to describe a flow cytometry sorting protocol based on UV-induced
autofluorescence. An EPICS ELITE ESP flow cytometer equipped with a UV laser and
cell sorter was used to mimic the optical properties of FLAPS and to study the
two extremes of a spore population according to its autofluorescence (lower level
of autofluorescence (LLA) and higher level of autofluorescence (HLA) spores).
Bacillus subtilis var niger was used as a surrogate for Bacillus anthracis spores
and sorted using autofluorescence intensity as the main criterion. The protocol
developed in our laboratory to sort Bacillus spores according to their
autofluorescence properties is described. Purity of each sorted population was
greater than 95%. Using autofluorescence as the main criterion, we demonstrate
that it is possible to separate two distinct spore populations.
PMID- 17031570
TI - Kinetic fluorimetric measurement of trace resorcinol in phenol mixtures.
AB - A kinetic spectrofluorimetric method was studied to measure the concentration of
trace resorcinol. The proposed method is based on the inhibitory effect of
resorcinol on the oxidation of rhodamine B by potassium bromate in the medium of
dilute sulfuric acid. The detection limit and linear range of the proposed
resorcinol measurement method are 12 microg L(-1) and 24 approximately 280 microg
L(-1), respectively. Relative standard derivations of eleven measurements for 80
microg L(-1) and 200 microg L(-1) resorcinol solutions are 2.12% and 1.08%,
respectively. The trace of resorcinol can be determined directly by the proposed
method without any pre-separation process when phenol and many other phenolic
compounds are present.
PMID- 17031568
TI - The development of a standardized neighborhood deprivation index.
AB - Census data are widely used for assessing neighborhood socioeconomic context.
Research using census data has been inconsistent in variable choice and usually
limited to single geographic areas. This paper seeks to a) outline a process for
developing a neighborhood deprivation index using principal components analysis
and b) demonstrate an example of its utility for identifying contextual variables
that are associated with perinatal health outcomes across diverse geographic
areas. Year 2000 U.S. Census and vital records birth data (1998-2001) were merged
at the census tract level for 19 cities (located in three states) and five
suburban counties (located in three states), which were used to create eight
study areas within four states. Census variables representing five socio
demographic domains previously associated with health outcomes, including
income/poverty, education, employment, housing, and occupation, were empirically
summarized using principal components analysis. The resulting first principal
component, hereafter referred to as neighborhood deprivation, accounted for 51 to
73% of the total variability across eight study areas. Component loadings were
consistent both within and across study areas (0.2-0.4), suggesting that each
variable contributes approximately equally to "deprivation" across diverse
geographies. The deprivation index was associated with the unadjusted prevalence
of preterm birth and low birth weight for white non-Hispanic and to a lesser
extent for black non-Hispanic women across the eight sites. The high correlations
between census variables, the inherent multidimensionality of constructs like
neighborhood deprivation, and the observed associations with birth outcomes
suggest the utility of using a deprivation, index for research into neighborhood
effects on adverse birth outcomes.
PMID- 17031571
TI - Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon
excitation.
AB - The series of novel monomer and homodimer styryl dyes based on (p
dimethylaminostyryl) benzothiazolium residues were synthesized and studied as
possible fluorescent probes for nucleic acids detection. Spectral-luminescent and
spectral-photometric properties of obtained dyes in the unbound state and in DNA
presence were studied. Fluorescence emission induced by two-photon excitation of
dye-DNA complexes in aqueous buffer solution was registered. Two-photon
absorption cross section values of the studied dyes in DNA presence were
evaluated.
PMID- 17031572
TI - Rotational diffusion and solvatochromic correlation of coumarin 6 laser dye.
AB - Rotational diffusion of coumarin 6 (C6) laser dye has been examined in n-decane
and methanol as a function of temperature. The rotational reorientation of this
probe has been measured in these solvents. It is observed that the decrease in
viscosity of the solution is responsible for the decrease in the rotational
relaxation time of the probe molecule. The molecule C6 has long reorientation
times in n-decane solvent as compared to methanol over all temperatures. It is
found that the coumarin 6 rotates slower in n-decane than in methanol especially
at higher values of viscosity over temperature. Two methods are chosen to
determine the ground state and excited state dipole moments. The change in dipole
moments is estimated from Bakhshiev-Chamma-Viallet equations and, the ground and
excited state dipole moments from Kawski et al. equations, by using the
variations of the Stokes shifts with the dielectric constant and refractive index
of the solvent. Our results are quite reliable which are solvatochromic
correlation obtained using solvent polarity functions. The reported results show
that excited state dipole moment is greater than ground state dipole moment,
which indicates that the excited state is more polar than the ground state.
PMID- 17031573
TI - Time-resolved FRET and FLIM of four-way DNA junctions.
AB - Conformational transitions in a 4-way DNA junction when titrated with ionic
solutions are studied using time-resolved fluorescence resonance energy transfer.
Parameters characterising the transition in terms of critical ion concentration
(c1/2) and the Hill coefficient for ion binding are obtained by fitting a simple
two-state model using steady-state spectra. Data obtained from a fluorescence
lifetime plate reader and analysed by fitting a single exponential to donor
fluorescence lifetime decays are shown to be in good agreement with the
parameters obtained from steady-state measurements. Fluorescence lifetimes,
however, offer advantages, particularly in being independent of fluorophore
concentration, output intensity, inhomogeneity in the excitation source and
output wavelength. We demonstrate preliminary FRET-FLIM images of DNA junction
solutions obtained using a picosecond gated CCD which are in agreement with
results from a fluorescence lifetime plate reader. The results suggest that time
resolved FRET-FLIM is sensitive to subtle structural changes and may be useful in
assays based on 4-way DNA junctions.
PMID- 17031574
TI - Ruby crystal for demonstrating time- and frequency-domain methods of fluorescence
lifetime measurements.
AB - We present experiments that are convenient and educational for measuring
fluorescence lifetimes with both time- and frequency-domain methods. The sample
is ruby crystal, which has a lifetime of about 3.5 milliseconds, and is easy to
use as a class-room demonstration. The experiments and methods of data analysis
are used in the lab section of a class on optical spectroscopy, where we go
through the theory and applications of fluorescence. Because the fluorescence
decay time of ruby is in the millisecond region, the instrumentation for this
experiment can be constructed easily and inexpensively compared to the nanosecond
resolved instrumentation required for most fluorescent compounds, which have
nanosecond fluorescence lifetimes. The methods are applicable to other
luminescent compounds with decay constants from microseconds and longer, such as
transition metal and lanthanide complexes and phosphorescent samples. The
experiments, which clearly demonstrate the theory and methods of measuring
temporally resolved fluorescence, are instructive and demonstrate what the
students have learned in the lectures without the distraction of highly
sophisticated instrumentation.
PMID- 17031575
TI - Overexpression of BLCAP induces S phase arrest and apoptosis independent of p53
and NF-kappaB in human tongue carcinoma : BLCAP overexpression induces S phase
arrest and apoptosis.
AB - Bladder cancer-associated protein gene (BLCAP) is a novel candidate tumor
suppressor gene identified from the human bladder carcinoma. Our previous studies
have shown that BLCAP overexpression could inhibit cell growth by inducing
apoptosis in HeLa cells [Zuo Z, Zhao M, Liu J, Gao G, Wu X: Tumor Biol 27: 221
226, 2006]. Such evidence suggests the alterations in BLCAP may play an important
role in tumorigenesis. To further study the biological function of the BLCAP
gene, we constructed a recombinant retroviral vector encoding BLCAP cDNA.
Overexpressed BLCAP, via stable infection of exogenous BLCAP, resulted in growth
inhibition of the human tongue cancer cell line Tca8113 in vitro, accompanied by
S phase cell cycle arrest and apoptosis. The growth inhibition was correlated
with up-regulation of p21(WAF1/CIP1 )expression and down-regulation of Bcl-XL and
Bcl-2 expressions. However, p53 expression and NF-kappaB activity remained
unchanged post infection. Furthermore, no changes in p53 phosphorylation at Ser46
and nuclear localization, which are critical to p53 function, were observed in
BLCAP-overexpressed cells. Taken together, BLCAP may play a role not only in
regulating cell proliferation but also in coordinating apoptosis and cell cycle
via a novel way independent of p53 and NF-kappaB.
PMID- 17031576
TI - Antiatherogenic and radioprotective role of folic acid in whole body gamma
irradiated mice.
AB - Free radical mediated oxidative damage is one of the prime factors for
atherogenic changes in humans. We have shown that the folic acid administration
reduced the risk of the atherogenic factors induced by gamma-radiation. Folic
acid administration prevented the radiation induced increase in the plasma
lipoprotein lipase activity and also prevented the radiation-induced increase in
the hepatic cholesterol and triglycerides levels. These results indicate the role
of folic acid as an antiatherogenic agent. Further, we also report the
radioprotective property of folic acid as demonstrated by reduction in the
radiation induced membrane damage as measured by lipid peroxidation products and
DNA damage, which was measured by alkaline comet assay.
PMID- 17031577
TI - MMP-2 and MMP-9 activity is regulated by estradiol and tamoxifen in cultured
human breast cancer cells.
AB - Sex steroids play a dominant role in breast carcinogenesis by still largely
unknown mechanisms. Matrix metalloproteinases (MMPs) have been extensively
studied in the context of matrix biology but it is not known if sex steroids
affect MMPs in breast cancer. MMPs degrade extracellular matrix components
enabling tumor cell invasion and metastasis, but may also regulate the
bioavailability of a variety of biologically active molecules such as anti
angiogenic fragments, which may be beneficial for the host. This study shows that
estradiol and tamoxifen regulate MMP-2 and MMP-9 as well as TIMP-1 and TIMP-2 in
ER + PR + human breast cancer cells. The main finding was a significant effect of
tamoxifen exposure, which increased intracellular and secreted protein levels
whereas estradiol induced a significant decrease. The overall net effect of these
alterations resulted in increased MMP-2/MMP-9 activity by tamoxifen treatment,
which also significantly increased extracellular endostatin levels. We conclude
that estradiol and tamoxifen have the ability to modulate MMP-2/MMP-9 activity,
and endostatin levels in human breast cancer in vitro. The results suggest a
possible role of MMP modulation associated with a generation of anti-angiogenic
fragments in the therapeutic effect of tamoxifen in breast cancer.
PMID- 17031578
TI - Factors in the delayed HIV presentation of immigrants in Northern California:
implications for voluntary counseling and testing programs.
AB - To describe the determinants of delayed HIV presentation in one Northern
California County, the authors identify persons with an opportunistic infection
(OI) at HIV diagnosis. From 2000-2002, a sample of HIV patients attending a
public AIDS program (n=391) were identified. Immigrants composed 24% of our
sample; 78.7% of immigrants were Hispanic. Immigrants, compared to U.S.-born
patients, presented with lower initial CD4+ counts at diagnosis than U.S.-born
patients (287 cells/mm(3) vs. 333 cells/mm(3), p=0.143), were more likely to have
an OI at HIV diagnosis (29.8% vs. 17.2%, p=0.009), and were more likely to be
hospitalized at HIV diagnosis (20.2% vs. 12.5%, p=0.064). We found only immigrant
status was significantly and independently associated with delayed presentation.
Interviews with 20 newly HIV diagnosed Hispanic patients suggest lack of
knowledge regarding HIV risk, social stigma, secrecy and symptom driven health
seeking behavior all contribute to delayed clinical presentation. The main
precipitants of HIV testing for immigrants were HIV/AIDS related symptoms and
sexually transmitted infection (STI)/HIV diagnosis in a sexual partner. These
results support augmentation of STI/HIV voluntary clinical testing and partner
notification services along the Mexico-California migrant corridor.
PMID- 17031579
TI - Lengthier cryoablation and a bonus cryoapplication is associated with improved
efficacy for cryothermal catheter ablation of supraventricular tachycardias in
children.
AB - INTRODUCTION: Cryoablation is an effective treatment for children with
supraventricular tachycardias (SVT). The present study documents the effect of
two different cryoablation protocols on acute and chronic success rates. METHODS
AND RESULTS: Fifty-three consecutive patients (age range, 5-20 years) were
treated; patients 1 to 17 were treated by a standard ablation protocol and
patients 18 to 53 were treated by a modified ablation protocol that required
lengthier cryoablations plus delivery of a bonus cryoapplication to consolidate
the acutely successful irreversible lesion created at intervention.
Electrophysiological study (EPS) was performed with diagnostic catheters and
cryoablations were performed with a 7FR 4 mm tip catheter (CryoCath
Technologies). Acute endpoints for non-inducibility of atrioventricular nodal re
entrant tachycardia (AVNRT) by programmed atrial stimulation at baseline or
during isoproterenol performed 30 min post procedure, as well as non-inducibility
and conduction block over the accessory pathway (AP). The chronic endpoint was
arrhythmia recurrence post intervention. No permanent cryo-related complications
or adverse outcomes were reported. Acute success rates for patients 1 to 17 and
18 to 53 were 88 and 100%, respectively. The cumulative percentage of patients
without arrhythmia recurrence at 12 month follow-up was significantly different
at 73 and 90%, respectively. CONCLUSIONS: Lengthier cryoablation delivery,
approximating 7 min per cryoablation, increases the acute success rate at
intervention. Moreover, these lengthier cryoablation deliveries plus a bonus
cryoapplication to consolidate the acutely successful irreversible lesion created
at intervention may also significantly improve the chronic success rate, while
also maintaining an excellent safety profile for cryoablation treatment of
children with SVT such as AVNRT and AP located near the AV junction.
PMID- 17031580
TI - Electrical and hemodynamic function produced by stimulation of atropine sensitive
right ventricular nerves in humans.
AB - In mammalian ventricles including humans, it is recognized that parasympathetic
ganglia innervate the heart. Little is known about the location and function of
right ventricular parasympathetic nerves in humans. We hypothesized that in
humans: (1) there are parasympathetic ganglia that supply the right ventricle
that can be stimulated via an endocardial catheter and (2) stimulation of these
fibers will alter the electrical and hemodynamic function of the right ventricle.
Parasympathetic nerve stimulation was performed via an endocardial catheter
placed along several sites of the right ventricle, superior vena cava, and right
internal jugular area in humans. The spatial extent of parasympathetic
innervation was mapped in 1-cm zones across the right ventricle. Cardiac output,
heart rate, and atrioventricular conduction were monitored to provide independent
assessment of parasympathetic innervation. In all 22 patients, ventricular
refractoriness shortened from 12 +/- 3 to 3 +/- 1 ms during parasympathetic nerve
stimulation, and the greatest shortening of refractoriness was observed at the
base of the right ventricle (p = 0.01). No significant shortening in ventricular
refractoriness occurred in areas beyond 2 cm from the right ventricular base.
These results were compared by using T table test. The parasympathetic nerve
stimulation protocol decreased cardiac output, reaffirming the principle effect
of parasympathetic ganglia. Atropine was administered in seven patients. All
effects from nerve stimulation were abolished after atropine administration.
These results were also compared by using T table test. These data provide the
first demonstration of the electrical and hemodynamic function by stimulation of
atropine sensitive nerves of the human right ventricle. Greater understanding of
parasympathetic innervation may lead to novel therapies for arrhythmias.
PMID- 17031581
TI - Child care health consultation programs: barriers and recommendations.
AB - OBJECTIVES: While many studies describe the need for health services in early
care and education (ECE) settings and the role of child care health consultants
(CCHCs), little information exists about the challenges to developing health
consultation programs. The goal of this paper is to provide insight for the
development of current and future child care health consultation programs by
describing the barriers identified by CCHCs related to program implementation in
20 California counties. METHODS: Forty-four child care health consultants
participated in nine focus groups during their health consultation training at
the California Training Institute. Participants were asked to discuss the
barriers they encountered while establishing new county-wide child care health
consultation programs. Themes were assigned to each response, and frequency and
percentage of each theme were documented and trends were identified. RESULTS: The
four general themes describing barriers to program implementation were: Program
Management, Child Care Culture, Geography and Community Services. Twenty
additional sub-themes, including Multi-agency involvement, Chaos, Travel time,
and Fragmentation, were assigned to each response. The most frequent general
theme was Program Management. The most frequent sub-theme was Professional
Support. CONCLUSIONS: The barriers identified by the child care health
consultants can be valuable for administrators and clinicians establishing or
developing child care health consultation programs. Program managers should be
prepared for the unique challenges of child care health consultation and provide
flexibility and support for child care health consultants.
PMID- 17031582
TI - Increasing access to program information: a strategy for improving adolescent
health.
AB - OBJECTIVES: To identify existing programs serving 11- to 15-year-olds that aim to
improve adolescent health in the areas of Health & Well-being, Fitness, Family &
Peer Relationships, School Environment, Smoking, Alcohol Use, and Violence and to
assess the utility of readily available resources in providing detailed program
information. METHODS: In Phase 1, publicly available program databases were
searched to identify potential programs serving the target population. In Phase
2, an in-depth search of a limited sample of programs meeting the content and age
criteria was performed to identify program descriptors. RESULTS: Over 1,000
program names were identified in Phase 1. Information regarding programs is
becoming more readily available through the internet; however, the program
information that was publicly available only begins to draw the picture. Phase 2
revealed that a broad array of efforts are underway in all seven content areas,
but found information on the program descriptors to be limited. CONCLUSIONS:
Investment in programming is not enough; an upfront investment in communication
and information sharing is critical in order to maximize the resources dedicated
to the improvement of adolescent health. A well-publicized centralized program
repository offered in conjunction with technical assistance would provide an
efficient mechanism for this information sharing. We further suggest that the
inherent gap between research and practice can be lessened by building a new body
of practice knowledge. This would require improved program data collection by
programs, the incorporation of program participation information in national
surveys and enhanced evaluation efforts.
PMID- 17031583
TI - Dyspareunia, urinary sensory symptoms, and incontinence among young Chinese
women.
AB - This study examined the prevalence of dyspareunia, urinary sensory symptoms, and
urinary incontinence and explored their associations among sexually active
Chinese women aged 15-34 years. Data from 3,150 women were analyzed from a survey
undertaken during 2003 in 30 counties in China as part of the United Nations
Population Fund Country Program. The overall prevalence of dyspareunia was 4.7%.
Urinary pain, burning or frequency was reported by 8.5%, 6.2% reported urinary
incontinence, and 2.3% reported both sets of urinary symptoms. The prevalence of
urinary incontinence, both alone and in combination with sensory symptoms,
increased in a linear manner with age. Dyspareunia was associated with early
sexual debut, primary level of education, and membership of minority ethnic
communities. Urinary sensory symptoms and incontinence were more common among
those reporting early sexual debut, those with less schooling, and women engaged
in agricultural and manual unskilled occupations. Urinary incontinence was more
common among women who had had a previous vaginal delivery compared to
nulliparous women. Dyspareunia was strongly associated with the presence of
urinary symptoms, particularly among those with both sensory symptoms and
incontinence (26.8%). Nearly a quarter of women who had dyspareunia had sought
treatment but fewer had done so for urinary incontinence. Dyspareunia and urinary
symptoms show distinct but overlapping patterns of association with demographic
variables. The findings indicate unmet need for assessment and advice about these
symptoms in women's reproductive health programs.
PMID- 17031585
TI - Detection of differential viewing patterns to erotic and non-erotic stimuli using
eye-tracking methodology.
AB - As a first step in the investigation of the role of visual attention in the
processing of erotic stimuli, eye-tracking methodology was employed to measure
eye movements during erotic scene presentation. Because eye-tracking is a novel
methodology in sexuality research, we attempted to determine whether the eye
tracker could detect differences (should they exist) in visual attention to
erotic and non-erotic scenes. A total of 20 men and 20 women were presented with
a series of erotic and non-erotic images and tracked their eye movements during
image presentation. Comparisons between erotic and non-erotic image groups showed
significant differences on two of three dependent measures of visual attention
(number of fixations and total time) in both men and women. As hypothesized,
there was a significant Stimulus x Scene Region interaction, indicating that
participants visually attended to the body more in the erotic stimuli than in the
non-erotic stimuli, as evidenced by a greater number of fixations and longer
total time devoted to that region. These findings provide support for the
application of eye-tracking methodology as a measure of visual attentional
capture in sexuality research. Future applications of this methodology to expand
our knowledge of the role of cognition in sexuality are suggested.
PMID- 17031586
TI - Psychometric properties of the Turkish version of the internalized homophobia
scale.
AB - The current study examined the psychometric properties of the Turkish version of
the Internalized Homophobia Scale (IHS; Herek, Cogan, Gillis, & Glunt, 1997) in
gay men living in Turkey. Participants were 132 men in romantic, intimate, or
sexual relationships with men, and they identified themselves as homosexual
(n=112) or bisexual (n=20). Alpha and split-half reliability coefficients
revealed good internal consistency of the scale. Consistent with the original
scale, the construct validity revealed a single factor for the scale. Regarding
convergent validity, the IHS had significant correlations with psychological
problems, particularly with symptoms of depression and anxiety; the scale also
had a significant positive correlation with negative affect and a negative
correlation with self-esteem. Regarding discriminant validity, the IHS had very
low correlations with positive affect and hostility attitudes. The association
between internalized homophobia and psychological problems remained significant
even after controlling for the variance explained by self-esteem, negative
affect, and positive affect. Hence, the psychometric properties of the Turkish
version of IHS appear quite promising.
PMID- 17031588
TI - Obesity, body image, and unsafe sex in men who have sex with men.
AB - Little is known about the relationship among body weight, body image, and
HIV/AIDS sexual risk behaviors. We examined this issue in a midwestern U.S.
metropolitan area community sample of 316 men who have sex with men, a group at
relatively high risk for HIV/AIDS. All data were self-reported by questionnaire
using standard items to assess current body image, height and weight, and
HIV/AIDS sexual risk behaviors. Logistic regression models were used to estimate
cross-sectional associations. Forty-nine (15%) of the 316 men were classified as
obese, and 56 (18%) had unsafe sex in the past three months. Normal weight or
overweight men were 3.6 times more likely than obese men to have had unsafe sex,
after adjusting for differences in body image and age. Men with better body image
were 1.4 times more likely than men with lower body image to have had anal sex,
after adjusting for differences in body weight and age. Non-obese men were no
more or less likely than were obese men to have engaged in anal sex or in any sex
in the past three months. This is the first study showing a positive relationship
between below-obese body weight and unsafe sex and between better body image and
anal sex in men who have sex with men. Future research should investigate these
novel findings, perhaps using other study designs and data collection tools with
less measurement error. Advances in knowledge about HIV/AIDS risk factors,
including body weight and body image, could potentially contribute to more
effective approaches to reducing this risk.
PMID- 17031589
TI - Painful sexual intercourse caused by a disproportionately long penis: an
historical note on a remarkable treatment devised by Guilhelmius Fabricius
Hildanus (1560-1634).
AB - Between 1598 and 1641, the famous surgeon Guilhelmius Fabricius Hildanus (1560
1634) published 600 medical and surgical observations in his Observationum et
curationum chirurgicarum centuriae I-VI. One of the case reports bears the title
'Pain and infertility caused by a too large penis.' The woman described in this
case report most likely suffered from positional deep dyspareunia. Hildanus
invented in 1593 a remarkable made-to-measure device. This device was a very well
considered and faultless curative for the woman's dyspareunia. It seemed that the
dyspareunia had a simple cause: the disproportional large penis of the woman's
husband. Four hundred years later, Hildanus' forgotten penis shortening device
deserves a resurrection in today's medical practice. This remarkable and almost
forgotten case report is described and discussed.
PMID- 17031590
TI - Assessment of sexual functioning, mental health, and life goals in women with
vaginal agenesis.
AB - Vaginal agenesis is a congenital disorder defined by the incomplete formation of
the vagina and other reproductive organs, often including the cervix, uterus, and
fallopian tubes. For the patient, this frequently means infertility and an
underdeveloped vagina with the subsequent difficulty to have vaginal intercourse.
The patient with vaginal agenesis and her family then encounter a variety of
psychological concerns that must be addressed during diagnosis, including
weighing treatment options, managing interventions, and coping with long-term
issues following diagnosis and treatment, such as partnership concerns and
infertility. In this study, seven patients between the ages of 18 and 34
completed questionnaires assessing demographic information, sexual functioning,
mental health, self-esteem, and life goals. Sexual functioning results were
highly variable. Participants reported significant emotional reactions at
diagnosis as well as anxiety about the disorder, specifically its role in
relationships. However, overall, the group showed average levels of mental health
and self-esteem. Participants also showed positive coping techniques through
conceptualization of life goals.
PMID- 17031591
TI - Psychological symptomatology among Palestinian male and female adolescents living
under political violence 2004-2005.
AB - The aim of the study was to investigate gender differences in relation to
exposure to domestic violence, political violence, family relations and
psychological symptomatology in Palestinian adolescents. The sample consisted of
1766 adolescents, males (54.1%) and females (45.9%), residents of West Bank
cities subjected to violent political conflict. Participants completed a self
report questionnaire consisting of the following measures: demographic variables,
domestic violence, political violence events, the McMaster Family Assessment
Device, and the Brief Symptom Inventory (BSI) psychological symptomatology.
Results indicated that whereas there was no significant difference in the level
of exposure to political violence between boys and girls, female adolescents
exhibited higher levels of psychological symptoms compared to their male
counterparts. Girls also reported higher levels of exposure to domestic violence
and lower levels of family function than boys.
PMID- 17031592
TI - Autonomous reovirus strain classification using filament-coupled antibodies.
AB - We previously described a filament-based antibody recognition assay (FARA) that
generates ELISA-like sandwich structures immobilized on a filament. FARA allows
the coupling of antibodies to precise locations along a filament, on-line
fluorescence detection of captured pathogen, and feedback-directed filament
motion. These properties suggest that this approach might be useful as an
automated means to rapidly classify unknown pathogens. In this report, we
describe validation of the novel decision tree aspect of this technology using
mammalian reovirus. Based on available antibodies, we developed a decision tree
algorithm to detect virus with increasing specificity at each level of the tree.
Using three strains of reovirus and a bacteriophage control, our system correctly
classified the reovirus strains at a concentration of 2 x 10(12) virions ml(-1)
and M13K07 phage at 3 x 10(11) virions ml(-1). Classification of reovirus strain
type 3 Dearing (T3D) required three levels of testing: general reovirus
classification in level 1, serotype 3 classification in level 2, and final T3D
strain classification in level 3. Strain T3SA + also required three levels of
testing before a final classification was returned in level 3. Classification of
strain type 1 Lang (T1L) required two levels of testing. M13K07 phage detection
required only one level of testing for classification. These results indicate
that automated pathogen classification using FARA is feasible. Furthermore, the
simplicity of the design could be exploited for development of more complex sub
classification networks with additional levels and branches.
PMID- 17031593
TI - Evaluation of important treatment parameters in supraphysiological thermal
therapy of human liver cancer HepG2 cells.
AB - This study was aimed at simulating the effect of various treatment parameters
like heating rate (HR), peak temperature (PT) and hold/total treatment time on
the viability of human liver cancer HepG2 cells subjected to different thermal
therapy conditions. The problem was approached by investigating the injury
kinetics obtained using experimentally measured viability of the cells, heated to
temperatures of 50-70 degrees C for 0-9 min at HRs of 100, 200, 300 and 525
degrees C min(-1). An empirical expression obtained between the activation energy
(E) and HR was extended to obtain the E values over a broad range of HRs from 5
to 600 degrees C min(-1) that mimic the actual conditions encountered in a
typical thermal therapy protocol. Further, the effect of the HR (5-600 degrees C
min(-1)) and PT (50-85 degrees C) on the cell survival was studied over a range
of hold times. A significant drop in survival from 90% to 0% with the
simultaneous increase in HR and PT was observed as the hold time increased from 0
to 5 min. For complete cell death, the hold time increased with the increase in
the HR for a given PT, while the total time showed presence of minima for 60, 65
and 70 degrees C at HRs of 50, 100 and 200 degrees C min(-1), respectively.
PMID- 17031594
TI - Optimisation of biochemical condition and substrates in vitro for tissue
engineering of ligament.
AB - In this work, we analysed the effect of growth factors on in vitro cell
proliferation and collagens synthesis by fibroblasts cultured for 72 h on
different substrates (silicon sheet with or without 1% gelatin, and glass as
control surface) for ligament tissue engineering. A human fibroblast cell line
(CRL-2703) was used. The synthesis of type I and type III collagens were
evaluated qualitatively and quantitatively by RT-PCR and confocal microscopy,
respectively. Cell proliferation was evaluated by two methods: (1) MTT assay (2)
cell cycle analysis. It was found that PDGF-AB stimulate the proliferation of
fibroblast cultured on gelatin coated silicon sheet in dose dependant manner with
a maximum effect at 10 ng ml(-1). The exogenous TGF-beta1 induced the expression
of type I and type III collagens in a dose and substrate-dependant manner. We
deduce from this work that biochemical conditions and substrates have an
important impact for optimisation of the tissue neo synthesis.
PMID- 17031595
TI - NFAT and NFkappaB activation in T lymphocytes: a model of differential activation
of gene expression.
AB - Mathematical models for the regulation of the Ca(2+)-dependent transcription
factors NFAT and NFkappaB that are involved in the activation of the immune and
inflammatory responses in T lymphocytes have been developed. These pathways are
important targets for drugs, which act as powerful immunosuppressants by
suppressing activation of NFAT and NFkappaB in T cells. The models simulate
activation and deactivation over physiological concentrations of Ca(2+), diacyl
glycerol (DAG), and PKCtheta using single and periodic step increases. The model
suggests the following: (1) the activation NFAT does not occur at low frequencies
as NFAT requires calcineurin activated by Ca(2+) to remain dephosphorylated and
in the nucleus; (2) NFkappaB is activated at lower Ca(2+) oscillation frequencies
than NFAT as IkappaB is degraded in response to elevations in Ca(2+) allowing
free NFkappaB to translocate into the nucleus; and (3) the degradation of IkappaB
is essential for efficient translocation of NFkappaB to the nucleus. Through
sensitivity analysis, the model also suggests that the largest controlling factor
for NFAT activation is the dissociation/reassociation rate of the
NFAT:calcineurin complex and the translocation rate of the complex into the
nucleus and for NFkappaB is the degradation/resynthesis rate of IkappaB and the
import rate of IkappaB into the nucleus.
PMID- 17031596
TI - Proteoglycan breakdown of meniscal explants following dynamic compression using a
novel bioreactor.
AB - Motivated by our interest in examining meniscal mechanotransduction processes, we
report on the validation of a new tissue engineering bioreactor. This paper
describes the design and performance capabilities of a tissue engineering
bioreactor for cyclic compression of meniscal explants. We showed that the system
maintains a tissue culture environment equivalent to that provided by
conventional incubators and that its strain output was uniform and reproducible.
The system incorporates a linear actuator and load cell aligned together in a
frame that is contained within an incubator and allows for large loads and small
displacements. A plunger with six Teflon-filled Delrin compression rods is
attached to the actuator compressing up to six tissue explants simultaneously and
with even pressure. The bioreactor system was used to study proteoglycan (PG)
breakdown in porcine meniscal explants following various input loading tests (0
20% strain, 0-0.1 MPa). The greatest PG breakdown was measured following 20%
compressive strain. These strain and stress levels have been shown to correspond
to partial meniscectomy. Thus, these data suggest that removing 30-60% of
meniscal tissue will result in the breakdown of meniscal tissue proteoglycans.
PMID- 17031597
TI - Single-step 3-d image reconstruction in magnetic induction tomography:
theoretical limits of spatial resolution and contrast to noise ratio.
AB - Magnetic induction tomography (MIT) is a low-resolution imaging modality for
reconstructing the changes of the complex conductivity in an object. MIT is based
on determining the perturbation of an alternating magnetic field, which is
coupled from several excitation coils to the object. The conductivity
distribution is reconstructed from the corresponding voltage changes induced in
several receiver coils. Potential medical applications comprise the continuous,
non-invasive monitoring of tissue alterations which are reflected in the change
of the conductivity, e.g. edema, ventilation disorders, wound healing and
ischemic processes. MIT requires the solution of an ill-posed inverse eddy
current problem. A linearized version of this problem was solved for 16
excitation coils and 32 receiver coils with a model of two spherical
perturbations within a cylindrical phantom. The method was tested with simulated
measurement data. Images were reconstructed with a regularized single-step Gauss
Newton approach. Theoretical limits for spatial resolution and contrast/noise
ratio were calculated and compared with the empirical results from a Monte-Carlo
study. The conductivity perturbations inside a homogeneous cylinder were
localized for a SNR between 44 and 64 dB. The results prove the feasibility of
difference imaging with MIT and give some quantitative data on the limitations of
the method.
PMID- 17031599
TI - Three-dimensional numerical modeling and computational fluid dynamics simulations
to analyze and improve oxygen availability in the AMC bioartificial liver.
AB - A numerical model to investigate fluid flow and oxygen (O(2)) transport and
consumption in the AMC-Bioartificial Liver (AMC-BAL) was developed and applied to
two representative micro models of the AMC-BAL with two different gas capillary
patterns, each combined with two proposed hepatocyte distributions. Parameter
studies were performed on each configuration to gain insight in fluid flow, shear
stress distribution and oxygen availability in the AMC-BAL. We assessed the
function of the internal oxygenator, the effect of changes in hepatocyte oxygen
consumption parameters in time and the effect of the change from an experimental
to a clinical setting. In addition, different methodologies were studied to
improve cellular oxygen availability, i.e. external oxygenation of culture
medium, culture medium flow rate, culture gas oxygen content (pO(2)) and the
number of oxygenation capillaries. Standard operating conditions did not
adequately provide all hepatocytes in the AMC-BAL with sufficient oxygen to
maintain O(2) consumption at minimally 90% of maximal uptake rate. Cellular
oxygen availability was optimized by increasing the number of gas capillaries and
pO(2) of the oxygenation gas by a factor two. Pressure drop over the AMC-BAL and
maximal shear stresses were low and not considered to be harmful. This
information can be used to increase cellular efficiency and may ultimately lead
to a more productive AMC-BAL.
PMID- 17031598
TI - Bioactive hydrogel substrates: probing leukocyte receptor-ligand interactions in
parallel plate flow chamber studies.
AB - The binding of activated integrins on the surface of leukocytes facilitates the
adhesion of leukocytes to vascular endothelium during inflammation. Interactions
between selectins and their ligands mediate rolling, and are believed to play an
important role in leukocyte adhesion, though the minimal recognition motif
required for physiologic interactions is not known. We have developed a novel
system using poly(ethylene glycol) (PEG) hydrogels modified with either integrin
binding peptide sequences or the selectin ligand sialyl Lewis X (SLe(X)) within a
parallel plate flow chamber to examine the dynamics of leukocyte adhesion to
specific ligands. The adhesive peptide sequences arginine-glycine-aspartic acid
serine (RGDS) and leucine-aspartic acid-valine (LDV) as well as sialyl Lewis X
were bound to the surface of photopolymerized PEG diacrylate hydrogels.
Leukocytes perfused over these gels in a parallel plate flow chamber at
physiological shear rates demonstrate both rolling and firm adhesion, depending
on the identity and concentration of ligand bound to the hydrogel substrate. This
new system provides a unique polymer-based model for the study of interactions
between leukocytes and endothelium as well as a platform to develop improved
scaffolds for cardiovascular tissue engineering.
PMID- 17031600
TI - An ex vivo study of the biological properties of porcine aortic valves in
response to circumferential cyclic stretch.
AB - Normal physiological mechanical forces cause constant tissue renewal in aortic
valve leaflets (AVL) while altered mechanical forces incite changes in their
structural and biological properties. The current study aims at characterizing
the remodeling properties of AVL subjected to cyclic circumferential stretch in a
sterile ex vivo bioreactor. The leaflets cultured were stretched at a maximum
rate of 300%s(-1) corresponding to a 15% strain for 48 h. Collagen, sulfated
glycosaminoglycan (sGAG), and elastin contents of the stretched, fresh, and
statically incubated leaflets were measured. Cusp morphology and cell phenotype
were also examined. AVLs exposed to cyclic stretch showed a significant increase
in collagen content (p < 0.05) when compared to fresh and statically incubated
AVLs. sGAG content was significantly reduced in the stretched AVLs (p < 0.05)
when compared to the fresh leaflets and was comparable between stretched and
statically incubated AVLs. There was no statistically significant change in
elastin content in all the three groups of AVLs (p > 0.05). Native aortic valve
morphology was well preserved in stretched leaflets. Immunohistochemistry and
immunoblotting studies showed an increased expression of alpha-smooth muscle
actin (alpha-SMA) in stretched leaflets while alpha-SMA expression was reduced in
statically incubated AVLs when compared to the fresh leaflets. To conclude,
circumferential cyclic stretch altered the extracellular matrix remodeling
activity of valvular cells, and consequently the extracellular matrix composition
of the AVLs. Most interestingly, the contractile and fibrotic phenotypic
expression of valve interstitial cells was enhanced. These results show that
circumferential cyclic stretch is a possible mediator for AVL remodeling
activity.
PMID- 17031601
TI - Tannin composition affects the oxidative activities of tree leaves.
AB - We examined whether tannin composition plays an important role in explaining the
oxidative activities of tree leaves of Acer saccharum (sugar maple) and Quercus
rubra (red oak). Sugar maple leaves contained substantial amounts of
ellagitannins, condensed tannins, and galloyl glucoses, whereas red oak leaves
contained almost exclusively condensed tannins. Oxidative activities of the crude
phenolics from both species, and the phenolic fractions from sugar maple, were
measured with electron paramagnetic resonance (EPR) spectrometry and UV-visible
spectrophotometry. The two assays produced similar results: (1) sugar maple
phenolics produced larger semiquinone radical concentrations,and higher
semiquinone decay rates and browning rates than did red oak phenolics; (2)
ellagitannin levels were positively associated with the three measures of
oxidative activity; and (3) condensed tannin and galloyl glucose levels were
negatively associated with these measures. The negative relationship between
condensed tannin levels and oxidative activity resulted from the antioxidant
effects of condensed tannins on hydrolyzable tannins; several purified condensed
tannins significantly decreased the concentrations of semiquinone radicals and
browning rates of pedunculagin (an ellagitannin) and pentagalloyl glucose. As
expected, whole-leaf extracts from sugar maple produced elevated levels of
semiquinone radicals, but none were observed in red oak extracts when the two
species were compared with an EPR time-course assay. We conclude that the
oxidative activities of tree leaves may be affected by tannin composition, and
that the prooxidant activity of ellagitannins may be decreased by co-occurring
condensed tannins.
PMID- 17031602
TI - Neuroscience in Africa.
PMID- 17031603
TI - Physico-chemical changes in cladodes (nopalitos) from cultivated and wild cacti
(Opuntia spp.).
AB - Physico-chemical and nutritional composition from four different nopalitos (young
cladodes from cacti): Blanco sin Espinas, Blanco con Espinas, Verde Valtierrilla
(cultivated materials) and a wild material from the central region of Mexico were
studied at different sizes of harvesting. The first three are commercial crops.
None of the tested materials exhibited superior characteristics in all of the
evaluated parameters in relation to each one of them. In various cases properties
of the wild crop were comparable, if not superior, to commercial ones. Some
important changes were observed in total soluble solids, water content, texture,
acidity and pH as affected by size of cladode and specific crop. Most cladode
samples appear to be a good source of beta-carotene and lutein. The presence of
these compounds is important for human nutraceutical purposes.
PMID- 17031604
TI - Effect of DHA containing oils and powders on baking performance and quality of
white pan bread.
AB - Different sources of DHA and/or n-3 (omega-3) rich oils, oil emulsions and
microencapsulated (ME) powders were tested at two different concentrations with
the aim of producing fortified pan bread. Three oils (S-algae, fish and flax),
two emulsified algae oils (Emulsion-P and Emulsion-L) and two ME oils (ME-S algae
and ME-C algae) were compared. The DHA and n-3 oils replaced part of the
shortening in order to obtain 32 g slices enriched with 25 or 50 mg DHA, 35 or 70
mg total n-3 from fish oil and 90 or 180 mg linolenic from flax oil. Addition of
oils did not significantly affect water absorption but reduced mix time whereas
addition of the ME oils decreased both water absorption and mix time. Breads
enriched with flax or ME-C oils had lower volume and higher density than the
control, ME-S algae, Emulsion-P and Emulsion-L breads. All breads lost texture
throughout 14 d storage, the major changes occurred after 3 d. The ME-S algae oil
bread had the best softness after 14 d storage whereas breads produced from ME-S
algae or ME-C algae oils had the poorest texture. Sensory evaluations indicated
that the color of the ME-S algae oil fortified bread was significantly less
preferred than the other loaves. After 6 d the control bread had higher
acceptability compared with the rest of the breads enriched with high levels of
DHA or omega-3 oils. The high-enriched fish oil bread was well accepted during
the first days of storage but had the least preferred acceptability after 13 d.
The best fortified breads were those supplemented with S-algae oil, Emulsion-P
and Emulsion-L oils.
PMID- 17031605
TI - Hypoglycemic and hypocholesterolemic effects of Coptis chinensis franch
inflorescence.
AB - Hypocholesterolemic and hypoglycemic activities of Coptis chinensis franch
inflorescence (Coptis inflorescence) were studied using animal models. Serum
total and LDL cholesterol of rats fed a diet containing 1% cholesterol and 0.5%
cholic acid increased, as compared with those of rats fed a normal diet. The
level of total and LDL cholesterol were reduced markedly in a dose dependent
manner, in rats given Coptis inflorescence extract orally at doses of 0.25, 0.5
g/kg.day for 4 weeks. In diabetic rats induced by alloxan, Coptis inflorescence
extract showed a significant (p < 0.05) blood sugar lowering activity at all
experimented doses (0.125, 0.25 and 0.5 g/kg.day). The highest reduction of blood
sugar was about 58% when the rats were given Coptis inflorescence extract orally
at a dose of 0.5 g/kg.day for 3 weeks. The 100 g dried water extract of Coptis
inflorescence contained 8.11 g total alkaloid, 3.34 g berberin, 1.08 g palmatine
and 0.66 g jatrorrhizine, which had long been identified as active compounds in
Coptis chinensis franch root (Coptis root). Thus, the results suggest that Coptis
inflorescence would be effective in the prevention and management of coronary
artery disease by lowering serum cholesterol and blood sugar.
PMID- 17031606
TI - Assessing the generalization of psychopathy in a clinical sample of domestic
violence perpetrators.
AB - This study proposed that domestic violence perpetrators in a clinical sample
could be categorized into distinct subgroups and that a particular subgroup of
batterers would exhibit sufficient psychopathic characteristics to be clinically
meaningful. Participants were interviewed in order to gather a relevant social,
familial, educational, criminal, and substance abuse history. They were then
administered several psychological measures including the Psychopathy Checklist:
Screening Version (PCL:SV). Results lent support to the empirical batterer
typology identified by Holtzworth-Munroe, A., Meehan, J. C., Herron, K., Rehman,
U., & Stuart, G. L. (2000). However, despite the presence of a more antisocial
subgroup, psychopathy did not consistently differentiate among batterers across
the measured dependent variables.
PMID- 17031607
TI - An evaluation of contaminated estuarine sites using sediment quality guidelines
and ecological assessment methodologies.
AB - Toxic contaminants may enter estuarine ecosystems through a variety of pathways.
When sediment contaminant levels become sufficiently high, they may impact
resident biota. One approach to predict sediment-associated toxicity in estuarine
ecosystems involves the use of sediment quality guidelines (ERMs, ERLs) and site
specific contaminant chemistry while a second approach utilizes site-specific
ecological sampling to assess impacts at the population or community level. The
goal of this study was to utilize an integrated approach including chemical
contaminant analysis, sediment quality guidelines and grass shrimp population
monitoring to evaluate the impact of contaminants from industrial sources. Three
impacted sites and one reference site were selected for study. Grass shrimp
populations were sampled using a push-netting approach. Sediment samples were
collected at each site and analyzed for metals, polycyclic aromatic hydrocarbons
(PAHs), polychlorinated biphenyls (PCBs) and pesticides. Contaminant levels were
then compared to sediment quality guidelines. In general, grass shrimp population
densities at the sites decreased as the ERM quotients increased. Grass shrimp
densities were significantly reduced at the impacted site that had an ERM
exceedance for chromium and the highest Mean ERM quotient. Regression analysis
indicated that sediment chromium concentrations were negatively correlated with
grass shrimp density. Grass shrimp size was reduced at two sites with
intermediate levels of contamination. These findings support the use of both
sediment quality guidelines and site-specific population monitoring to evaluate
the impacts of sediment-associated contaminants in estuarine systems.
PMID- 17031608
TI - Soft tissue calcifications in the lower extremities of severely diabetic patients
simulating venous stasis or collagen vascular disease.
AB - The purpose of this work is to report soft tissue calcifications in severely
diabetic patients that simulate venous stasis or scleroderma, without other
stigmata of these diseases. Findings from lower extremity radiographs were
reviewed on two patients with severe diabetes mellitus and abnormal soft tissue
calcifications. Findings were correlated with clinical history, physical exam
findings, and laboratory values. Both patients in this study demonstrate
radiographic findings of lower extremity soft tissue calcifications similar to
those seen in venous stasis or scleroderma. Clinical history, physical
examination, and laboratory values support severe diabetes mellitus, with no
evidence of these other disease entities. Patients with severe diabetes mellitus
may exhibit soft tissue calcifications of their lower extremities that may
simulate the changes of venous stasis or scleroderma. This association has not
been previously described.
PMID- 17031609
TI - The introgression of chromosome 6P specifying for increased numbers of florets
and kernels from Agropyron cristatum into wheat.
AB - A wheat (Triticum aestivum L.) line 4844 with superior numbers of florets and
grains per spike was derived from the cross between Fukohokomugi wheat and
Agropyron cristatum (L.) Gaertn. In order to determine the genetic control of
floret and kernel number per spike in this line, chromosome addition and
substitution lines that were derived from line 4844 were characterized by means
of in situ hybridization, microsatellite (SSR), and gliadin analyses. Genomic in
situ hybridization analysis with biotinylated P genomic DNA of A. cristatum as a
probe demonstrated that the increased number of florets and grains in a spike was
associated with the introgression of an A. cristatum chromosome. Fluorescence in
situ hybridization, using a repetitive sequence, pAs1, derived from Aegilops
squarrosa L., indicated the replacement of chromosome 6D of wheat in the wheat-A.
cristatum chromosome substitution lines. This was confirmed by microsatellite
analyses with wheat SSR markers specific for chromosome 6D, suggesting that the
A. cristatum chromosome was homoeologous to group 6 and was therefore designated
as 6P. This conclvsion was further confirmed by amplification using EST-SSR
markers and gliadin analysis. The increased number of florets and kernels within
a spike of the wheat-A. cristatum hybrids thus was controlled by gene(s) located
on A. cristatum chromosome 6P.
PMID- 17031610
TI - Association of variants of transcription factor 7-like 2 (TCF7L2) with
susceptibility to type 2 diabetes in the Dutch Breda cohort.
AB - AIM/HYPOTHESIS: A strong association between susceptibility to type 2 diabetes
and common variants of transcription factor 7-like 2 (TCF7L2), encoding an
enteroendocrine transcription factor involved in glucose homeostasis, has been
reported in three different populations (Iceland, Denmark and USA) by Grant et
al. We aimed to replicate these findings in a Dutch cohort. METHODS: We analysed
the genotypes of two intronic single nucleotide polymorphisms (SNPs) in TCF7L2
gene in 502 unrelated type 2 diabetes patients and in a set of healthy controls
(n = 920). The two SNPs showed almost complete linkage disequilibrium (D' =
0.91). RESULTS: We were able to replicate the previously reported association in
our Breda cohort. The minor alleles of both variants were significantly over
represented in cases (odds ratio [OR] 1.29, 95% CI 1.09-1.52, [Formula: see text]
for rs12255372; OR 1.41, 95% CI 1.19-1.66, [Formula: see text] for rs7903146). In
addition, TCF7L2 haplotypes were analysed for association with the disease. The
analysis of haplotypes did not reveal any strong association beyond that expected
from analysing individual SNPs. The TT haplotype carrying the minor alleles was
more frequent among cases (OR 1.38, [Formula: see text]).
CONCLUSIONS/INTERPRETATION: Our data strongly confirm that variants of the TCF7L2
gene contribute to the risk of type 2 diabetes. The population-attributable risk
from this factor in the Dutch type 2 diabetes population is 10%.
PMID- 17031611
TI - Certifying diabetes-related cause-of-death: a comparison of inappropriate
certification statements in Sweden, Taiwan and the USA.
AB - AIMS/HYPOTHESIS: The aim of this study was to assess differences in the
certification practices of physicians in Sweden, Taiwan and the USA with regard
to diabetes-related cause-of-death (COD) statements. METHODS: Multiple-cause-of
death data from Sweden (2000), Taiwan (2001) and the USA (2001) were used for
this study. All deaths with mention of diabetes anywhere on the death certificate
were extracted for analysis. Two types of inappropriate COD statements were: (1)
reporting two or more diagnoses per line; and (2) entering an incorrect causal
sequence among reported diagnoses. RESULTS: Of those deaths in which diabetes was
reported in Part I of the death certificate, American physicians (19%) were less
likely to report two or more diagnoses per line than physicians in Sweden (46%)
and Taiwan (56%). On the other hand, Swedish physicians (5%) were less likely to
report incorrect causal sequences than were their counterparts in Taiwan (21%)
and the USA (28%). CONCLUSIONS/INTERPRETATION: These findings reveal substantial
differences in diabetes-related COD statements among physicians in Sweden, Taiwan
and the USA, implying that caution should be used when interpreting differences
in mortality statistics between these countries.
PMID- 17031612
TI - Change in the cross-sectional area of a patellar tendon graft after anterior
cruciate ligament reconstruction.
AB - The purpose of this study was to clarify the change in the cross-sectional area
(CSA) of a patellar tendon graft after anterior cruciate ligament (ACL)
reconstruction, and its relationship with postoperative knee laxity. Forty
patients (25 men and 15 women) were included in this study. Intraoperative CSA
measurements were performed with an instrumented areamicrometer, while a magnetic
resonance imaging (MRI) evaluation was utilized for the assessment
postoperatively. For intraoperative measurement, the average CSA of a 10-mm wide
patellar tendon graft was 32.3 +/- 7.0 mm2, while the average CSA measured at
follow-up (mean: 14.8 months) was 48.8 mm2, showing a significant mean increase
ratio of 49.4%. This value corresponded to 115% of the native ACL. The average
CSA measured in 30 patients at 6 months was 49.7 mm2, almost equal to the value
at the final follow-up (49.8 mm2) in the same patient group. Among potentially
influential factors, postoperative notch width (available space for the ACL
graft) had significant correlation with the CSA of the graft at follow-up.
Finally, both intra- and postoperative CSA values did not correlate with
postoperative knee laxity, indicating that a bigger graft does not guarantee a
better laxity.
PMID- 17031613
TI - Functional outcome and general health status in patients after arthroscopic
release in adhesive capsulitis.
AB - Frozen shoulder is said to be a self-limiting entity but full recovery often
takes more than 2 years. For that, most patients are unwilling to tolerate
painful restriction while awaiting resolution. We prospectively investigated 30
patients (16 women, 14 men) for the outcome of arthroscopic capsular release in
idiopathic frozen shoulder. Results were determined by the assessment of
subjective and objective parameters to estimate both shoulder function and
general health status. Symptoms persisted without improvement for a minimum of 6
months of conservative treatment. Preoperative average American shoulder and
elbow surgeons score (ASES) was 35, visual analog scale (VAS) to measure pain was
7, and simple shoulder test (SST) was 4. Mean scores of the physical component of
SF-36 were considerably reduced. Mean forward elevation was 85 degrees , average
abduction was 70 degrees , mean internal rotation was 15 degrees , and mean
external rotation was 10 degrees . Patients were followed-up at 6 weeks, 3, 6, 12
months and by a mean of 36 months. Range of motion for all planes improved (P <
0.05). Median VAS reduced to 2, average ASES increased to 91, and SST enhanced to
a mean of 10 (P < 0.05). We stated improvement of the physical components in the
SF-36 questionnaire in particular bodily pain and the role-physical score. There
were no significant differences between the measurements in the early
postoperative phase compared to the mid-term follow-up (P > 0.05). Our results
demonstrate that arthroscopic release of refractory idiopathic frozen shoulder
combined with a gentle manipulation provides reliable expectations for
improvement in both clinical and general health status for most patients. We
recommend the use of a limb-specific and a general-health-status questionnaire to
conclude the benefit of the surgical intervention and contribute the optimization
of a therapy concept more effectively.
PMID- 17031614
TI - In vitro measurement of patellar kinematics following reconstruction of the
medial patellofemoral ligament.
AB - This study compares the effects of two different techniques of medial
patellofemoral ligament (MPFL) reconstruction, and proximal soft tissue
realignment on patellar stabilization against lateral dislocation. Eight human
cadaver knee specimens with no radiological pathomorpholgy on a straight lateral
view, contributing to patellofemoral instability, were mounted in a kinematic
knee simulator and isokinetic extension was simulated. Patellar kinematics were
measured with an ultrasound positioning system (zebris) while a 100 N laterally
directed force was applied to the patella. The kinematics were compared with
intact knee conditions under MPFL deficient conditions, as well as following
dynamic reconstruction of the MPFL using a distal transfer of the semitendinosus
tendon, following static reconstruction by a semitendinosus autograft, and
following proximal soft tissue realignment of the patella (Insall procedure).
Dynamic reconstruction of the MPFL resulted in no significant alteration (P =
0.16) of patellar kinematics. Static reconstruction of the MPFL significantly
medialized (P < 0.01) the patellar movement without, but restored intact knee
kinematics under the laterally directed force. In contrast, following proximal
soft tissue realignment, the patellar movement was constantly medialized and
internally tilted (P = 0.04). Dynamic and static reconstruction of the MPFL
create sufficient stabilization of the patella. Following proximal soft tissue
realignment, the patellar position was over-medialized relative to intact knee
conditions, which could lead to an overuse of the medial retropatellar cartilage.
PMID- 17031615
TI - Induction of alpha-L-arabinofuranosidase activity by monomeric carbohydrates in
Bifidobacterium longum and ubiquity of encoding genes.
AB - Bifidobacterium longum can be isolated from human faeces, some strains being
considered probiotics. B. longum NIZO B667 produces an exo-acting alpha-L
arabinofuranosidase, AbfB, previously purified by us, that releases L-arabinose
from arabinan and arabinoxylan. This activity was subjected to two-seven-fold
induction by L-arabinose, D-xylose, L-arabitol and xylitol and to repression by
glucose. Maximum activity was obtained at 48 h incubation except for D-xylose
that was at 24 h. High concentrations (200 mM) of L-arabitol also caused
repression of the arabinofuranosidase. A unique band of activity showing the same
migration pattern as the purified AbfB was found in zymograms of cell free
extracts, indicating that the activity was likely due to this sole enzyme. The
assessment of the influence of inducers and repressors on the activity of AbfB
and on the expression of the abfB gene by real time PCR indicated that regulation
was transcriptional. DNA amplifications using a pair of degenerated primers
flanking an internal fragment within alpha-L-arabinofuranosidase genes of the
family 51 of glycoside hydrolases evidenced that these enzymes are widespread in
Bifidobacterium. The aminoacidic sequences of bifidobacteria included a fragment
of four to six residues in the position 136-141 that was absent in other
microorganisms.
PMID- 17031616
TI - Bacteriocin-like inhibitor substances produced by Mexican strains of Bacillus
thuringiensis.
AB - Bacteriocins are antimicrobial peptides synthesized and secreted by bacteria and
could potentially be used as natural food preservatives. Here, we report the
production of bacteriocin-like inhibitor substances (Bt-BLIS) by five Mexican
strains of Bacillus thuringiensis. Bacillus thuringiensis subsp. morrisoni (LBIT
269), B. thuringiensis subsp. kurstaki (LBIT 287), B. thuringiensis subsp kenyae
(LBIT 404), B. thuringiensis subsp. entomocidus (LBIT 420) and B. thuringiensis
subsp. tolworthi (LBIT 524) produced proteinaceous Bt-BLIS with high levels of
activity against Bacillus cereus and other gram-positive bacteria. Although none
was active against the gram-negative bacteria, Escherichia coli, Shigella species
and Pseudomonas aeruginosa, the five Bt-BLIS demonstrated antimicrobial activity
against Vibrio cholerae, the etiologic agent of cholera. Biochemical and
biophysical studies demonstrated that the five Bt-BLIS could be categorized into
two groups, those produced by LBIT 269 and 287 (Group A) and LBIT 404, 420, 524
(Group B), based on relative time of peptide synthesis, distinctive bacterial
target specificity and stability in a wide range of temperatures and pH. Because
of their stability and bactericidal activities against B. cereus and V. cholerae
agents of emetic, diarrheal and lethal syndromes in humans, these Bt-BLIS could
potentially be used as biodegradable preservatives in the food industry.
PMID- 17031617
TI - Biotransformation of mercury in pH-stat cultures of eukaryotic freshwater algae.
AB - Eukaryotic algae were studied to determine their ability to biotransform Hg(II)
under aerated and pH controlled conditions. All algae converted Hg(II) into beta
HgS and Hg(0) to varying degrees. When Hg(II) was administered as HgCl(2) to the
algae, biotransformation by species of Chlorophyceae (Selenastrum minutum and
Chlorella fusca var. fusca) was initiated with beta-HgS synthesis (K (1/2) of
hours) and concomitant Hg degrees evolution occurred in the first hour. Hg
degrees synthesis was impeded by the formation of beta-HgS and this inhibition
was released in C. fusca var. fusca when cellular thiols were oxidized by the
addition of dimethylfumarate (DMF). The diatom, Navicula pelliculosa
(Bacillariophyceae), converted a substantially greater proportion of the applied
Hg(II) into Hg(0), whereas the thermophilic alga, Galdieria sulphuraria
(Cyanidiophyceae), rapidly biotransformed as much as 90% of applied Hg(II) into
beta-HgS (K (1/2) approximately 20 min). This thermophile was also able to
generate Hg(0) even after all exogenously applied HgCl(2) had been
biotransformed. The results suggest that beta-HgS may be the major dietary
mercurial for grazers of contaminated eukaryotic algae.
PMID- 17031618
TI - Sporotalea propionica gen. nov. sp. nov., a hydrogen-oxidizing, oxygen-reducing,
propionigenic firmicute from the intestinal tract of a soil-feeding termite.
AB - An unusual propionigenic bacterium was isolated from the intestinal tract of the
soil-feeding termite Thoracotermes macrothorax. Strain TmPN3 is a motile, long
rod that stains gram-positive, but reacts gram-negative in the KOH test. It forms
terminal endospores and ferments lactate, glucose, lactose, fructose, and
pyruvate to propionate and acetate via the methyl-malonyl-CoA pathway. Propionate
and acetate are formed at a ratio of 2:1, typical of most propionigenic bacteria.
Under a H(2)/CO(2) atmosphere, the fermentation product pattern of glucose,
fructose, and pyruvate shifts towards propionate formation at the expense of
acetate. Cell suspensions reduce oxygen with lactate, glucose, glycerol, or
hydrogen as electron donor. In the presence of oxygen, the product pattern of
lactate fermentation shifts from propionate to acetate production. 16S rRNA gene
sequence analysis showed that strain TmPN3 is a firmicute that clusters among the
Acidaminococcaceae, a subgroup of the Clostridiales comprising obligately
anaerobic, often endospore-forming bacteria that possess an outer membrane. Based
on phenotypic differences and less than 92% sequence similarity to the 16S rRNA
gene sequence of its closest relative, the termite hindgut isolate Acetonema
longum, strain TmPN3(T) is proposed as the type species of a new genus,
Sporotalea propionica gen. nov. sp. nov. (DSM 13327(T), ATCC BAA-626(T)).
PMID- 17031620
TI - Recent developments in optical detection methods for microchip separations.
AB - This paper summarizes the features and performances of optical detection systems
currently applied in order to monitor separations on microchip devices.
Fluorescence detection, which delivers very high sensitivity and selectivity, is
still the most widely applied method of detection. Instruments utilizing laser
induced fluorescence (LIF) and lamp-based fluorescence along with recent
applications of light-emitting diodes (LED) as excitation sources are also
covered in this paper. Since chemiluminescence detection can be achieved using
extremely simple devices which no longer require light sources and optical
components for focusing and collimation, interesting approaches based on this
technique are presented, too. Although UV/vis absorbance is a detection method
that is commonly used in standard desktop electrophoresis and liquid
chromatography instruments, it has not yet reached the same level of popularity
for microchip applications. Current applications of UV/vis absorbance detection
to microchip separations and innovative approaches that increase sensitivity are
described. This article, which contains 85 references, focuses on developments
and applications published within the last three years, points out exciting new
approaches, and provides future perspectives on this field.
PMID- 17031619
TI - Phytotoxicity assessment of diclofenac and its phototransformation products.
AB - The occurrence of pharmaceuticals in the environment is an emerging issue.
Several studies observed that the non-steroidal anti-inflammatory drug diclofenac
is ubiquitously present in most of the surveyed surface waters, worldwide.
Phototransformation of diclofenac was reported from laboratory assays as well as
in natural water systems, raising the question of possible adverse effects of the
phototransformation products of diclofenac to aquatic organisms. In this study
the phytotoxicity of diclofenac exposed to natural sunlight was evaluated using
synchronized cultures of the unicellular chlorophyte Scenedesmus vacuolatus.
Diclofenac dissolved in ultra-pure water at 50 mg L(-1) was exposed to natural
midsummer sunlight for a maximum of 145 h. Twice a day subsamples were taken for
chromatography and parallel phytotoxicity assessment. Inhibition of algal
reproduction of the initial diclofenac solution was in the mg L(-1) range
indicating no specific toxicity of diclofenac towards S. vacuolatus. Fast
degradation of diclofenac was observed with half lives between 3.3 and 6.4 h
during the first and the third day of exposure, respectively. Phytotoxicity
increased after 3.5 h of exposure of diclofenac to sunlight and showed a maximum
of sixfold enhanced toxicity after 53 h of exposure to sunlight. Several
phototransformation products were found during the experiment. The time courses
of the relative concentration of three transformation products significantly
correlated with enhanced phytotoxicity during the experiment. This indicates a
high toxicity potential of phototransformation products of diclofenac at
concentration levels that may come close to environmental concentrations of
residual diclofenac after degradation. We conclude that toxicity assessment of
phototransformation products should be included in the risk assessment of
pharmaceuticals in the environment.
PMID- 17031621
TI - Study of normal colorectal tissue by FT-Raman spectroscopy.
AB - FT-Raman spectroscopy was employed to study normal human colorectal tissues in
vitro with the aim of evaluating the spectral differences of the complex colon
mucous in order to establish a characteristic Raman spectrum. The samples were
collected from 39 patients, providing 144 spectra for the statistical analysis.
The results enable one to establish three well-defined spectroscopic groups of
non-altered colorectal tissues that were consistently checked by statistical
(clustering) and biological (histopathology) analyses: group 1 is represented by
samples with the presence of epithelial layer, connective tissue papillae, and
smooth muscle tissue; group 2 comprises tissues with epithelial layer and
connective tissue papillae; group 3 presented mostly fatty and slack conjunctive
tissue. The study reveals the existence of an intrinsic spectral variability for
each patient that must be considered when sampling tissues fragments to build a
spectral database. This is the first step for future studies and applications of
Raman spectroscopy to optical biopsy and diagnosis of colorectal cancer.
PMID- 17031622
TI - Occurrence and analysis of pharmaceuticals and their transformation products in
drinking water treatment.
PMID- 17031623
TI - A rapid analytical method for predicting the oxygen demand of wastewater.
AB - In this study, an investigation was undertaken to determine whether the
predictive accuracy of an indirect, multiwavelength spectroscopic technique for
rapidly determining oxygen demand (OD) values is affected by the use of
unfiltered and turbid samples, as well as by the use of absorbance values
measured below 200 nm. The rapid OD technique was developed that uses UV-Vis
spectroscopy and artificial neural networks (ANNs) to indirectly determine
chemical oxygen demand (COD) levels. It was found that the most accurate results
were obtained when a spectral range of 190-350 nm was provided as data input to
the ANN, and when using unfiltered samples below a turbidity range of 150 NTU.
This is because high correlations of above 0.90 were obtained with the data using
the standard COD method. This indicates that samples can be measured directly
without the additional need for preprocessing by filtering. Samples with
turbidity values higher than 150 NTU were found to produce poor correlations with
the standard COD method, which made them unsuitable for accurate, real-time, on
line monitoring of OD levels.
PMID- 17031624
TI - Determination of pharmaceuticals from different therapeutic classes in
wastewaters by liquid chromatography-electrospray ionization-tandem mass
spectrometry.
AB - A sensitive analytical method has been developed and validated for simultaneous
determination of pharmaceuticals from different therapeutic classes, i.e. five
sulfonamide (SA) and trimethoprim antimicrobials and the anti-inflammatory drug
diclofenac, in effluent wastewaters at trace levels. Effluent samples from
treatment of wastewater were enriched by solid-phase extraction (SPE) using the
Waters Oasis HLB cartridge. The analytes were identified and quantified by
reversed-phase liquid chromatography-tandem mass spectrometry operated in the
selected reaction monitoring (SRM) mode, using positive electrospray ionization.
The pharmaceuticals were, consequently, quantified both by use of isotopically
labelled internal standards and by standard addition methods to address the issue
of matrix effects related to signal suppression by co-eluting compounds. Average
recoveries from fortified samples were usually >70%, with relative standard
deviations below 20%. Method detection limits in wastewater matrices were between
7.0 and 10 ng L(-1). Identification points (IPs) were used for unequivocal
identification of target analytes in real samples. Diclofenac, trimethoprim, and
sulfamethoxazole were mainly detected, in the concentration range 10 to 400 ng L(
1), in effluent samples collected from four different sewage-treatment plants in
Greece.
PMID- 17031625
TI - Stacked films immobilization of MBTH in nafion/sol-gel silicate and horseradish
peroxidase in chitosan for the determination of phenolic compounds.
AB - The stacked-film immobilization of 3-methyl-2-benzothiazolinone hydrazone (MBTH)
in hybrid nafion/sol-gel silicate film and horseradish peroxidase (HRP) in
chitosan, performed in order to allow the determination of phenolic compounds,
was investigated via an optical method. The stacked films were deposited onto a
microscope glass slide by a spin-coating technique. The quinone or free radical
product formed by the enzymatic reactions of phenolic compounds interacts with
MBTH to form azo-dye products, which can be measured spectrophotometrically at a
wavelength of 500 nm. The color intensity of the product was found to increase in
proportion to the phenolic concentration after 5 min of exposure. The response of
the biosensor was linear over concentration ranges of 0.025-0.500, 0.010-0.070
and 0.050-0.300 mM for guaiacol, resorcinol and o-cresol, respectively, and gave
detection limits of 0.010, 0.005 and 0.012 mM. The sensor exhibited good
sensitivity and stability for at least two months.
PMID- 17031626
TI - Microstructure and chemical composition of giant avian eggshells.
AB - The microstructure and composition of the layers of two giant avian eggshells
were investigated using a combination of scanning electron microscopy, electron
probe microanalyses, and X-ray absorption near-edge structure spectroscopy
(XANES). The two species have some similarities and differences in their
microstructure and composition; the composition is not homogeneous throughout the
eggshell thickness. XANES studies show that sulfur is associated with amino acids
in the inner organic membranes, whereas in the mineralised layers the sulfur is
mainly associated with sulfated polysaccharides. These results are similar to
those obtained on chicken eggshells, and confirm the active role of sulfated
acidic polysaccharides in biomineralisation processes of carbonate skeletons.
PMID- 17031627
TI - Observation of salt-induced beta-lactoglobulin aggregation using sedimentation
field-flow fractionation.
AB - Sedimentation field-flow fractionation (SdFFF) was applied in order to
characterize particle sizes of beta-lactoglobulin aggregates induced by Ca2+ or
Zn2+. Aggregation induced by Zn2+ was faster than that induced by Ca2+. Effects
of Zn2+ and beta-lactoglobulin concentrations, as well as contact time, on the
aggregation of beta-lactoglobulin were examined. All factors exhibited a combined
effect on the size of aggregates, whereby larger aggregates were obtained at
increased concentrations of Zn2+ and beta-lactoglobulin. At fixed concentrations
of 2% (w/v) beta-lactoglobulin and 10 mM Zn2+, the particle size of the
aggregates increased from 0.19 microm (at 15 min) to 0.38 microm (at 2880 min).
Further, a hyphenated technique of SdFFF and inductively coupled plasma-optical
emission spectrometry (ICP-OES) was used to examine whether intermolecular ionic
bridges take part in salt-induced beta-lactoglobulin aggregation. With SdFFF-ICP
OES, protein-cation-protein cross-linkages were observed for beta-lactoglobulin
aggregation induced by Zn2+, but not for that induced by Ca2+.
PMID- 17031628
TI - Fiber-optic flow-through sensor for online monitoring of glucose.
AB - A new microdialysis-based glucose-sensing system with an integrated fiber-optic
hybrid sensor is presented. Design and dimensions of the cell are adapted for its
coupling with commercially available microdialysis techniques, thereby providing
a new system for continuous glucose monitoring. The glucose level is detected via
oxygen consumption which occurs as a consequence of enzymatic reaction between
immobilized glucose oxidase and glucose. The use of gas-permeable Tygon tubing
ensures complete and constant air-saturation of the measuring fluid in the cell.
Nevertheless, a reference oxygen optode is used to detect and to compensate
response changes caused by events like bacterial growth, temperature
fluctuations, or failure of the peristaltic pump. In contrast to widely used
electrochemical sensors, the response of the microdialysis-based fiber-optic
glucose sensor is highly selective, making this sensor approach particularly
advantageous for continuous glucose monitoring of patients in intensive care
units. The effects of flow rate, pH, temperature, and common interferences on the
sensor response are presented and discussed in detail. The sensor is evaluated in
vitro using a 3-day continuous test in glucose-spiked plasma. The ability to
measure glucose in humans is demonstrated by coupling the flow-through cell and
commercially available microdialysis catheter CMA60. A 24-h monitoring test using
this setup is successfully applied to a healthy volunteer.
PMID- 17031629
TI - Kinetic speciation of nickel in mining and municipal effluents.
AB - This study presents the results of kinetic speciation of nickel in undiluted
mining and municipal effluents and effluents diluted with receiving freshwaters
from the surrounding environment. The dilution ratios used for the dilution of
the effluents were arbitrarily chosen, but were representative of the prevailing
mining practices. The purpose of the this dilution was to mimic dilution with
natural waters that result from dilution of the mining and municipal effluents
with receiving freshwaters, so that this study would reveal environmental
realities that are of concern to the managers and regulators of water resources.
Ligand exchange kinetics using the competing ligand exchange method (CLEM) was
studied using two independent techniques: graphite furnace atomic absorption
spectrometry (GFAAS) with Chelex 100 resin as the competing ligand, and
adsorptive cathodic stripping voltammetry (AdCSV) with dimethylglyoxime (DMG) as
the competing ligand to determine the percentage of Ni metal released from Ni(II)
DOC complexes and the rate of dissociation of Ni(II)-DOC complexes. Using a
sample containing a mixture of 30% Copper Cliff Mine effluent, 40% Sudbury
municipal effluent and 30% Vermillion River water, both techniques gave results
showing that the dilution of the effluent samples increased the percentage of
nickel released from Ni(II)-DOC complexes. This increase in the release of nickel
from the Ni(II)-DOC complexes may be of concern to managers and regulators of
water resources. Agreement between the results of these two techniques has
enhanced the validity of the competing ligand exchange method used by both
techniques.
PMID- 17031630
TI - Scanning electron microscopy and energy dispersive analysis: applications in the
field of cultural heritage.
AB - Scanning electron microscopy has been extensively used for the material
characterization of objects of artistic and archaeological importance, especially
in combination with energy dispersive X-ray microanalysis (SEM/EDX). The
advantages and limitations of SEM/EDX are presented in a few case studies:
analysis of pigments in cross-sections of paint layers, quantitative analysis of
archaeological glass from the Roman period excavated in Ephesos/Turkey, and
investigations on glasses with medieval composition concerning their weathering
stability and degradation phenomena.
PMID- 17031631
TI - Metabolic imaging of atrophic muscle tissue using appropriate markers in 1H and
31P NMR spectroscopy.
AB - INTRODUCTION: The purpose of this feasibility study was to demonstrate non
invasive metabolic imaging of human muscular atrophy using significant changes of
NMR signals that are related directly or indirectly to fiber necrosis. METHODS:
Single-voxel (1)H NMR spectroscopy and two-dimensional (31)P spectroscopic
imaging on a 1.5-T whole-body scanner were used for in vivo mapping of areas of
muscle damage in two cases of differently localized and pronounced atrophy.
Spectral patterns affiliated with severe and intermediate stages of degeneration
were compared to data of healthy control tissue to derive appropriate metabolic
markers related to lipid infiltration or high-energy (31)P metabolism. RESULTS:
Reliable detection of atrophic tissue was achieved by the following parameters:
(1) liposclerotic turnover is related to a drastic reduction in the water/lipid
(1)H signal intensity ratio (up to a factor of 74 compared to adjacent healthy
tissue); (2) the (31)P resonance of phosphocreatine (PCr) is an adequate marker
for differentiation of intact myocells with high-energy metabolism from regions
dominated by terminal fiber necrosis (PCr signal vanished nearly completely or
intensity was reduced by a factor of 3 in affected muscles). Metabolic images
based on this signal allowed accurate non-invasive localization of atrophic
tissue. CONCLUSION: The molecular information provided by NMR spectroscopy-
previously only used with poor localization in atrophy studies--enables access to
both the myocell-specific high-energy metabolism and the result of lipid
infiltration allowing non-invasive mapping of degenerate tissue. The ability to
investigate the results of these advanced levels of atrophy would also be useful
for studies of more subtle degrees of denervation.
PMID- 17031632
TI - Cavernous haemangioma of the spermatic cord in a child.
AB - We present a unique case of an 11-year-old boy with a cavernous haemangioma of
the spermatic cord. Sonography showed a well-defined, heterogeneous echoic mass
with internal calcifications in the paratesticular region while radiography
showed several phleboliths in the scrotum. Both were helpful in differentiating
this paratesticular tumour.
PMID- 17031633
TI - Evaluation of tumour necrosis during chemotherapy with diffusion-weighted MR
imaging: preliminary results in osteosarcomas.
AB - BACKGROUND: During successful chemotherapy of osteosarcomas tumour size does not
diminish significantly because the therapy has limited impact on the mineralized
matrix of the tumour. Treatment response is considered successful if,
histologically, more than 90% of tumour cells show necrosis. OBJECTIVE: To
determine if osteosarcomas change their water diffusion during preoperative
chemotherapy in relation to the amount of tumour necrosis. MATERIALS AND METHODS:
Eight patients (age 11-19 years) with histologically proven limb osteosarcoma
underwent T1-weighted, fat-suppressed T2-weighted and contrast-enhanced T1
weighted spin-echo imaging together with diffusion-weighted EPI sequences (b =
700) at 1.5 T before and after five cycles of standard chemotherapy. Tumour
volume and apparent diffusion coefficient (ADC) maps were calculated before and
after chemotherapy. The degree of tumour necrosis after chemotherapy was assessed
using the histological Salzer-Kuntschik classification (grades 1-6). RESULTS:
During chemotherapy, the ADC values of osteosarcomas changed significantly. The
ADC of untreated tumour was 2.1 +/- 0.4 x 10(-3) mm(2)/s (mean +/- SD) (95% CI
1.6-2.0). The ADC of chemotherapy-treated sarcomas was 2.5 +/- 0.4 x 10(-3)
mm(2)/s (95% CI 1.8-2.2). Necrotic areas, which were confirmed by macroscopic
examination, showed ADC values up to 2.7 x 10(-3) mm(2)/s. Four patients with
little viable tumour tissue within the neoplasm (Salzer-Kuntschik grades 1-2) had
an increase in ADC of 0.4 up to 0.7 x 10(-3) mm(2)/s. Four patients with larger
areas of viable tumour (Salzer-Kuntschik grade 4) showed a lesser increase in ADC
of 0.0 up to 0.3 x 10(-3) mm(2)/s. The differences in ADC values in tumour tissue
before and after chemotherapy were highly significant (P = 0.01). CONCLUSION:
During chemotherapy of osteosarcomas, tumour ADC changes are related to the
degree of tumour necrosis.
PMID- 17031634
TI - Distribution of brain infarction in children with tuberculous meningitis and
correlation with outcome score at 6 months.
AB - BACKGROUND: Prognostic indicators for tuberculous meningitis (TBM) offer
realistic expectations for parents of affected children. Infarctions affecting
the basal ganglia are associated with a poor outcome. OBJECTIVE: To correlate the
distribution of infarction in children with TBM on CT with an outcome score (OS).
MATERIALS AND METHODS: CT brain scans in children with TBM were retrospectively
reviewed and the distribution of infarctions recorded. The degree of correlation
with OS at 6 months was determined. RESULTS: There was a statistically
significant association between all sites of infarction (P = 0.0001-0.001), other
than hemispheric (P = 0.35), and outcome score. There was also a statistically
significant association between all types of infarction (P = 0.0001-0.02), other
than hemispheric (P = 0.05), and overall poor outcome. The odds ratio for poor
outcome with bilateral basal ganglia and internal capsule infarction was 12. The
odds ratio for poor outcome with 'any infarction' was 4.91 (CI 2.24-10.74), with
'bilateral infarctions' 8.50 (CI 2.49-28.59), with basal ganglia infarction 5.73
(CI 2.60-12.64), and for hemispheric infarction 2.30 (CI 1.00-5.28). CONCLUSION:
Infarction is associated with a poor outcome unless purely hemispheric. MRI
diffusion-weighted imaging was not part of this study, but is likely to play a
central role in detecting infarctions not demonstrated by CT.
PMID- 17031635
TI - Pathology of the appendix in children: an institutional experience and review of
the literature.
AB - BACKGROUND: The appendix can be affected by a variety of congenital and acquired
diseases, but acute appendicitis is the most common pathology found in the
pediatric population. OBJECTIVE: This is a retrospective review of all
appendectomies performed during a 2-year period at a major children's hospital
with a review of the literature regarding the most common pathologic findings.
MATERIALS AND METHODS: The pathology database was reviewed for appendectomy
specimens, and patient medical records were evaluated to determine the age,
gender, race and operative diagnosis. All slides were reviewed and the histologic
findings were recorded. RESULTS: A total of 392 appendectomies were performed,
including 68 incidental appendectomies and 324 performed for clinical suspicion
of acute appendicitis. In 247 of the latter, acute appendicitis was confirmed
histologically, and of the remainder 14 were interval appendectomies, 2 had
findings suspicious for Crohn disease, 1 confirmed diverticulitis and 60 were
histologically negative for appendicitis. CONCLUSION: Acute appendicitis is the
most common pathologic cause of appendectomy, but various other pathologic
entities are found in children. Examination of the appendix is warranted even
when it appears normal on exploration.
PMID- 17031636
TI - Biochemical characterization of a novel 2-Cys peroxiredoxin from Antrodia
camphorata.
AB - Peroxiredoxins (Prxs) play important roles in antioxidation and cell signaling. A
gene encoding a novel 2-Cys Prx was identified based on sequence homology in an
expressed sequence tag database of the Antrodia camphorata, a medicinal mushroom
found only in Taiwan. The 2-Cys Prx cDNA (940 bp) encodes a protein of 188 amino
acid residues with calculated molecular mass of 20,965 Da and a pI of 5.89. The
coding region was subcloned into pAVD10, transformed into Escherichia coli, and
expressed as a His-tagged fusion protein. The purified enzyme was characterized
under various conditions. The Prx retained 68% activity after being heated at 60
degrees C for 2 min. It was stable under a broad pH range from 5 to 11. The
enzyme activity was slightly decreased in the presence of 1% sodium dodecyl
sulfate. The enzyme was somewhat susceptible to chymotrypsin treatment but
resistant to digestion by trypsin.
PMID- 17031637
TI - Effect of aniline coupling on kinetic and thermodynamic properties of Fusarium
solani glucoamylase.
AB - Purified glucoamylase (GA) from Fusarium solani was chemically modified by cross
linking with aniline hydrochloride in the presence of 1-ethyl-3-(3
dimethylaminopropyl) carbodiimide (EDC) for 1 [aniline-coupled glucoamylase-1
(ACG-1)], 7 (ACG-7), and 13 min (ACG-13). The aniline coupling of GA had a
profound enhancing effect on temperature, pH optima, and pK (a)'s of active site
residues. The specificity constants (K (cat)/K (m)) of native, ACG-1, ACG-7, and
ACG-13 were 136, 244, 262, and 208 at 55 degrees C for starch, respectively. The
enthalpy of activation (DeltaH*) and free energy of activation (DeltaG*) for
soluble starch hydrolysis were lower for the chemically modified forms compared
to native GA. Proteolysis of ACGs by alpha-chymotrypsin and subtilisin resulted
in activation.
PMID- 17031638
TI - Sustained generation of electricity by the spore-forming, Gram-positive,
Desulfitobacterium hafniense strain DCB2.
AB - Desulfitobacterium hafniense strain DCB2 generates electricity in microbial fuel
cells (MFCs) when humic acids or the humate analog anthraquinone-2,6-disulfonate
(AQDS) is added as an electron-carrying mediator. When utilizing formate as fuel,
the Gram-positive, spore-forming bacterium generated up to 400 mW/m2 of cathode
surface area in a single-chamber MFC with a platinum-containing air-fed cathode.
Hydrogen, lactate, pyruvate, and ethanol supported electricity generation, but
acetate, propionate, and butyrate did not. Scanning electron microscopy indicated
that strain DCB2 colonized the surface of a current-generating anode but not of
an unconnected electrode. The electricity was recovered fully within minutes
after the exchange of the medium in the anode chamber and within a week after an
exposure of a colonized anode to 90 degrees C for 20 min. Of the six strains of
Desulfitobacteria tested, all of which would reduce AQDS, only D. hafniense
strain DCB2 continued to reduce AQDS and generate electricity for more than 24 h,
indicating that reduction of the humate analog alone is insufficient to sustain
electrode reduction.
PMID- 17031639
TI - Differential regulation of manganese peroxidases and characterization of two
variable MnP encoding genes in the white-rot fungus Physisporinus rivulosus.
AB - Manganese peroxidase (MnP) production in the white-rot basidiomycete
Physisporinus rivulosus T241i was studied. Separate MnP isoforms were produced in
carbon-limited liquid media supplemented with Mn(2+), veratryl alcohol, or
sawdust. The isoforms had different pH ranges for the oxidation of Mn(2+) and 2,6
dimethoxyphenol. Although lignin degradation by white-rot fungi is often
triggered by nitrogen depletion, MnPs of P. rivulosus were efficiently produced
also in the presence of high-nutrient nitrogen, especially in cultures
supplemented with veratryl alcohol. Two MnP encoding genes, mnpA and mnpB, were
identified, and their corresponding cDNAs were characterized. Structurally, the
genes showed marked dissimilarity, and the expression of the two genes implicated
quantitative variation and differential regulation in response to manganese,
veratryl alcohol, or sawdust. The variability in regulation and properties of the
isoforms may widen the operating range for efficient lignin degradation by P.
rivulosus.
PMID- 17031640
TI - Vaccination therapy in prostate cancer.
AB - Radical prostatectomy and radiation therapy provide excellent localized prostate
cancer (PC) control. Although the majority of prostate carcinoma is nowadays
diagnosed at early stages with favourable risk features, in patients up to 30-40%
it recurs within 10 years. Furthermore, the lack of effective therapies, once
prostate carcinoma becomes refractory to androgen deprivation, mandates the
development of alternative therapeutic options. There is a growing interest in
harnessing the potency and specificity of anti-tumour immunity through the
generation of fully competent dendritic cells and tumour reactive effector
lymphocytes. Several strategies to treat or prevent the development of metastatic
PC have been explored in clinical trials and are summarized in this review,
considering also the feasibility and safety of these approaches. In some cases
clinical responses were achieved showing that vaccine-primed T cells induced anti
tumour activity in vivo. The present findings and perspectives of the immunologic
interventions in PC patients will be discussed.
PMID- 17031641
TI - N-acetylneuraminic acid coupled human recombinant TNFalpha exhibits enhanced anti
tumor activity against Meth-A fibrosarcoma and reduced toxicity.
AB - In order to study the effect of glycosylation on its biological activities and to
develop tumor necrosis factor alpha (TNFalpha) with less deleterious effects, N
acetylneuraminic acid (NeuAc) with a C9 spacer was chemically coupled to human
recombinant TNFalpha. NeuAc-coupled TNFalpha (NeuAc-TNFalpha) exhibited reduced
activities in vitro by about threefold compared to native TNFalpha. In this
study, we examined a variety of TNFalpha activities in vivo. NeuAc-TNFalpha
reduced activities in the up-regulation of serum levels of IL-6 and NOx, but
comparable activity as native TNFalpha in the down-regulation of the serum level
of glucose. However, NeuAc-TNFalpha was more potent than TNFalpha in the up
regulation of the serum level of serum amyloid A (SAA). NeuAc-TNFalpha was less
toxic to mice. In addition, NeuAc-TNFalpha exhibited an augmented anti-tumor
activity against Meth-A fibrosarcoma without hemorrhagic necrosis. These results
indicate that coupling with NeuAc enabled us to develop neoglycoTNFalpha with
selective activities in vivo, including enhanced anti-tumor activity but reduced
toxicity.
PMID- 17031642
TI - Synthesis of glycosylated human tumor necrosis factor alpha coupled with N
acetylneuraminic acid.
AB - In order to study the effect of glycosylation on its biological activities, and
to develop TNFalpha with less deleterious effects, recombinant human TNFalpha was
chemically coupled with N-acetylneuraminic acid (NeuAc). NeuAc with C9 spacer was
coupled to TNFalpha by acyl azide method. Two glycosylated TNFalphas, designated
L NeuAc-TNFalpha and H NeuAc-TNFalpha, were purified by anion-exchange
chromatography. NeuAc coupling to TNFalpha was confirmed by lectin blotting.
Average number of carbohydrate molecules introduced per molecule of L NeuAc
TNFalpha and H NeuAc-TNFalpha were estimated to be 1.0 and 1.5, respectively. We
examined a variety of TNFalpha activities in vitro, including antiproliferative
or cytotoxic activities to tumor cells, proliferative effect on fibroblast cells,
stimulatory effects on IL-6 production by melanoma cells and NF-kappaB activation
in hepatoma cells. L NeuAc-TNFalpha and H NeuAc-TNFalpha exhibited reduced
activities about 1/3 and 1/10 as compared to native TNFalpha in all the
activities performed in vitro.
PMID- 17031643
TI - Docetaxel/gemcitabine or cisplatin/gemcitabine followed by docetaxel in the first
line treatment of patients with metastatic non-small cell lung cancer (NSCLC):
results of a multicentre randomized phase II trial.
AB - BACKGROUND: Most patients (pts) with metastatic non-small cell lung cancer
(NSCLC) receive either single agents or chemotherapy doublets. Recent studies
have demonstrated that triple-agent therapies may improve the response rate, but
are associated with significant toxicity, and frequently do not prolong survival.
A sequential triple-agent schedule may combine acceptable tolerability and good
efficacy. We therefore conducted a multicentre, prospectively randomized study
that evaluates a sequential three-drug schedule and a platinum-free doublet
regimen. PATIENTS AND METHODS: The pts with union international contre le cancer
(UICC) stage IV NSCLC were randomized to one of two schedules: in arm Doc-Gem,
they received gemcitabine (900 mg/m(2), 30 min infusion) on days 1 and 8, and
docetaxel (75 mg/m(2), 1 h infusion) on day 1, repeated every 3 weeks up to six
cycles. In arm Cis-Gem-->Doc, gemcitabine (900 mg/m(2), days 1 and 8) and
cisplatin (70 mg/m(2), 1 h infusion, day 1) were given for three cycles, followed
by three cycles of docetaxel (100 mg/m(2), day 1, repeated every 3 weeks).
RESULTS: One hundred and thirteen pts were randomized to arms Doc-Gem (55 pts)
and Cis-Gem-->Doc (58 pts). With Doc-Gem, 20.4% of pts responded to the treatment
whereas 31.0% responded in arm Cis-Gem-->Doc (overall response, intent-to-treat,
difference not significant). The median time to progression was 3.6 months in arm
Doc-Gem [95% confidence interval (CI) 1.4, 5.9] and 5.2 months in arm Cis-Gem-
>Doc (95% CI 3.1, 7.3). The median survival was 8.7 months with treatment Doc-Gem
(95% CI 5.7, 11.6) and 9.4 months with treatment Cis-Gem-->Doc (95% CI 7.8,
11.0). The 1-year survival rates were 34 and 35%, respectively. Mild to moderate
leukopenia was frequently seen with both schedules. Other common adverse events
(AE) were nausea/vomiting, thrombocytopenia, anaemia, diarrhoea, and infections.
No significant differences in AEs were observed between the schedules except for
nausea/vomiting, which occurred more frequently with Cis-Gem-->Doc. CONCLUSION:
The sequential therapy comprising cisplatin, gemcitabine, and docetaxel
demonstrated promising tumour control whereas the platinum-free combination
(docetaxel/gemcitabine) was very well tolerated. However, the schedules resulted
in comparable survival to recent large trials in pts with advanced NSCLC. The
present results do not justify further phase III investigation.
PMID- 17031644
TI - Differential effects of the immunosuppressive agents cyclosporin A, tacrolimus
and sirolimus on drug transport by multidrug resistance proteins.
AB - PURPOSE: We sought to determine the effects of the immunosuppressants,
cyclosporin A (CsA), tacrolimus and sirolimus, on drug transport by the ATP
binding cassette proteins, P-glycoprotein (Pgp; ABCB1), multidrug resistance
protein-1 (MRP-1; ABCC1) and breast cancer resistance protein (BCRP; ABCG2), and
the major vault protein lung resistance protein (LRP). METHODS: Cellular content
of mitoxantrone, a Pgp, MRP-1 and BCRP substrate, was measured by flow cytometry
in cells overexpressing these proteins following incubation with and without CsA,
tacrolimus or sirolimus. Interaction of BCRP with these compounds was studied by
photolabeling and ATPase assays. Nuclear-cytoplasmic distribution of doxorubicin
was studied by confocal microscopy in cells overexpressing LRP. RESULTS: CsA
increased cellular drug uptake in cells overexpressing Pgp, MRP-1 or BCRP and
nuclear drug uptake in cells overexpressing LRP at the clinically achievable
concentration of 2.5 microM. Tacrolimus enhanced cellular drug uptake at 1
microM, but not at 0.08 microM, its clinically achievable concentration, and did
not enhance nuclear drug uptake. Sirolimus enhanced cellular drug uptake in cells
overexpressing Pgp, MRP-1 and BCRP with optimal effects at 2.5 microM, but was
effective at its clinically achievable concentration of 0.25 microM if cells were
pre-incubated for at least 30 min before drug exposure, and also enhanced nuclear
drug uptake at 0.25 microM. BCRP modulation by all three immunosuppressive agents
was associated with competitive binding to the drug transport sites. CONCLUSIONS:
CsA, tacrolimus and sirolimus modulate drug transport by Pgp, MRP-1 and BCRP and
CsA and sirolimus modulate drug transport by LRP at concentrations that differ
from immunosuppressive concentrations and maximum tolerated concentrations.
PMID- 17031645
TI - The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line.
AB - Cordycepin (3'-deoxyadenosine), a pure compound of Cordyceps sinensis, has been
illustrated with anti-tumor effects. In the present study, the apoptotic effect
of cordycepin on OEC-M1, a human oral squamous cancer cell line, was investigated
by morphological observations, cell viability assay, annexin V-FITC analysis and
flow cytometry methods. Results demonstrated that the number of rounded-up cell
increased as treatment duration of cordycepin (100 microM) increased from 3 to 48
h, and the plasma membrane blebbing could be observed after 12 h treatment. In
cell viability assay, cell surviving rate significantly decreased as the dosage
and duration of cordycepin treatment increased (P < 0.05). Moreover,
phosphatidylserine flipping on cell membrane could be detected with 3, 6 and 12 h
cordycepin treatment, which indicated an early apoptotic phenomenon. Furthermore,
cell cycle studies illustrated that the percentage of G1 phase cell declined as
the dosages of cordycepin increased (10 microM to 5 mM), while the percentages of
G2M and subG1 phase cell increased (P < 0.05) in 12, 24 and 48 h cordycepin
treatment. These results further confirmed the apoptotic event. In conclusion,
cordycepin significantly induced cell apoptotsis in OEC-M1 human oral squamous
cancer cells.
PMID- 17031646
TI - A phase I/randomized phase II, non-comparative, multicenter, open label trial of
CP-547,632 in combination with paclitaxel and carboplatin or paclitaxel and
carboplatin alone as first-line treatment for advanced non-small cell lung cancer
(NSCLC).
AB - PURPOSE: To evaluate the toxicity profile and pharmacological properties of oral
CP-547,632 alone and in combination with paclitaxel and carboplatin administered
every 3 weeks, and to assess efficacy as measured by the objective response and
progressive disease rates of oral CP-547,632 administered in combination with
paclitaxel and carboplatin. PATIENTS AND METHODS: Patients with stage IIIB/IV or
recurrent non-small cell lung cancer receiving first-line chemotherapy were
treated with oral daily CP-547,632 in combination with paclitaxel 225 mg/m(2) and
carboplatin AUC = 6 every 3 weeks. Pharmacokinetics parameters for CP-547,632 and
paclitaxel were determined independently and during co-administration. RESULTS:
Seventy patients were enrolled and 68 patients were treated, 37 in phase 1 and 31
in phase 2 (14 with the combination and 17 with chemotherapy alone). Dose
limiting toxicity of CP-547,632 250 mg by mouth daily in combination with
paclitaxel and carboplatin was grade 3 rash and grade 3 diarrhea despite medical
intervention. CP-547,632 did not significantly affect the pharmacologic profiles
of paclitaxel and carboplatin. No subject had CR. In phase I, seven subjects
(22.6%) had a confirmed partial response. In phase II, four subjects (28.6%)
receiving CP-547,632 plus chemotherapy had a confirmed partial response. In the
phase II chemotherapy alone group, four subjects (25%) had a confirmed partial
response. CONCLUSION: The combination of CP-547,632 and paclitaxel and
carboplatin was well-tolerated at doses up to 200 mg by mouth daily. Dose
limiting toxicity of CP-547,632 at 250 mg consisted of diarrhea and rash. CP
547,632 did not increase the objective response rate to chemotherapy alone in
patients with advanced non-small cell lung cancer.
PMID- 17031647
TI - Phase I dose-escalation study of a novel antitumor agent, SR271425, administered
intravenously in split doses (d1-d2-d3) in patients with refractory solid tumors.
AB - BACKGROUND: SR271425 is a novel DNA-binding cytotoxic agent with a broad spectrum
of antitumor activity in preclinical models,across a variety of the schedule of
administration. In toxicological studies, it has been reported to prolong QTc
proportionally to C (max). In order to circumvent this C (max)-related QTc
prolongation, 5 phase I studies were initiated to investigate 1-h, 24-h, weekly,
and split iv infusions. This phase I study assessed a split-dose regimen (a 1-h
infusion on each of Days 1 to 3, repeated every 3 weeks) to establish the dose
limiting toxicities (DLT), to recommended a phase II dose, and to characterize
PK/PD. METHODS: Patient with advanced solid tumors, adequate bone marrow,
hepatic, renal function and on specific cardiac criteria were eligible and "3 +
3" design was used for dose escalation. That dose escalation was guided by PK
data, toxicities observed and information from other ongoing phase I studies with
SR271425. SR271425 plasma levels (PK samples) were measured using a validated LC
MS/MS method. Careful monitoring of ECGs was done, and ECGs were read centrally.
RESULTS: Three centers enrolled 19 heavily pretreated patients to six dose
levels, from 75 to 450 mg/m(2)/day (i.e., 225-1,350 mg/m(2)/cycle): 12 males and
7 females. Median age 56. Median ECOG, PS = 1. Main tumor types were brain,
breast, gynecological, and urological. Patients received a median of 2 cycles
(range: 1-6). NCI-CTC Grade 1-2 toxicities included nausea, vomiting, asthenia,
rash, and yellow skin discoloration. No DLTs were reported, and there were no
dose-limiting prolongations of QTc. Both C (end) and AUC increased in a dose
related manner, with no evidence of accumulation between Day 1 and Day 3,
consistent with the mean (+/-SD) terminal elimination half-life of 5.11 +/- 1.21
h. Stable disease was observed in five cases. CONCLUSION: Split doses allow high
cumulative exposure to SR271425 without significant toxicity, especially without
QTc prolongation. MTD was not reached due to the early termination of the
SR271425 program by the sponsor.
PMID- 17031648
TI - Antitumor activity of trastuzumab in combination with chemotherapy in human
gastric cancer xenograft models.
AB - PURPOSE: To clarify the antitumor activity of trastuzumab and its potential as an
effective treatment for gastric cancer patients. METHODS: Levels of HER2
expression in tumor tissues of gastric cancer cell lines were examined using
immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and mRNA
quantification. Efficacy of trastuzumab was examined as a single agent or in
combination with chemotherapeutic agents widely used clinically for gastric
cancers in HER2-overexpressing human gastric cancer xenograft models. RESULTS:
Two of nine human gastric cancer xenograft models, NCI-N87 and 4-1ST, showed
overexpression of HER2 mRNA and protein by IHC (HercepTest) and HER2 gene
amplification by FISH (Pathvysion). HER2 protein showed potent staining in
peripheral membranes, similar to the staining pattern of breast cancer. FISH
scores were also comparable to those of breast cancer models. Trastuzumab as a
single agent inhibited the tumor growth in both of the HER2-overexpressing models
but not in the HER2-negative models, GXF97 and MKN-45. In any combination with
capecitabine, cisplatin, irinotecan, docetaxel, or paclitaxel, trastuzumab showed
more potent antitumor activity than the anticancer agents alone. A three-drug
combination of capecitabine, cisplatin, and trastuzumab showed remarkable tumor
growth inhibition. In NCI-N87 in vitro, trastuzumab showed direct
antiproliferative activity according to cell count or crystal violet dying, and
showed indirect antitumor activity such as antibody-dependent cellular
cytotoxicity. CONCLUSION: The antitumor activity of trastuzumab observed in human
gastric cancer models warrants consideration of its use in clinical treatment
regimens for human gastric cancer as a single agent or a combination drug with
various chemotherapeutic agents.
PMID- 17031649
TI - DNA vaccines for HIV: challenges and opportunities.
AB - In December 2005, the UNAIDS and WHO reported that the global epidemic known as
acquired immunodeficiency syndrome (AIDS) has claimed the lives of more than 25
million adults and children over the past 26 years. These figures included an
estimated 3.1 million AIDS-related deaths in 2005. Despite enormous efforts to
control the spread of human immunodeficiency virus (HIV) new infection rates are
on the rise. An estimated 40.3 million people are now living with HIV, including
4.9 million new infections this past year. Nearly half of new HIV infections are
in young people between the ages of 15 and 24. While drug therapies have helped
sustain the lives of infected individuals in wealthy regions, they are relatively
unavailable to the poorest global regions. This includes sub-Saharan Africa which
has approximately 25.8 million infected individuals, more than triple the number
of infections of any other region in the world. It is widely believed that the
greatest hope for controlling this devastating pandemic is a vaccine. In this
review, we will discuss the current state of DNA-based vaccines and how they
compare to other vaccination methods currently under investigation. We will also
discuss innovative ideas for enhancing DNA vaccine efficacy and the progress
being made toward developing an effective vaccine.
PMID- 17031650
TI - Therapeutic immunization for HIV.
AB - Vaccines have entered into human clinical trials against infectious diseases and
as therapies against cancer. The HIV virus establishes a latent infection at a
very early stage and the T cell memory of the infected patient is rapidly
destroyed. However, results of immunotherapy after DNA and protein immunization
show that vaccine-induced immune responses might be present for a long period of
time. Patients subjected to therapeutic immunization appear to do well, and to
have a small immunological advantage, which, however, will have to be improved.
The vaccine therapy should start early, while adequate reservoirs of appropriate
T helper cells are available and still inducible. The DNA vaccines induce a
relatively long-lived immunological memory, and gene-based immunization is
effective in inducing cytotoxic CD8(+) T cells and CD4+ helper cells. Protein
vaccines, on the other hand, primarily give T cell help. It thus appears that DNA
and protein approaches to HIV immunization complement each other. A surprisingly
broad reactivity to peptides from different subtypes of HIV was identified in
individuals infected with several subtypes of HIV.
PMID- 17031651
TI - Transgenic rice plants expressing trichothecene 3-O-acetyltransferase show
resistance to the Fusarium phytotoxin deoxynivalenol.
AB - Fusarium head blight (FHB) is a devastating disease of small grain cereal crops
caused by the necrotrophic pathogen Fusarium graminearum and Fusarium culmorum.
These fungi produce the trichothecene mycotoxin deoxynivalenol (DON) and its
derivatives, which enhance the disease development during their interactions with
host plants. For the self-protection, the trichothecene producer Fusarium species
have Tri101 encoding trichothecene 3-O-acetyltransferase. Although transgenic
expression of Tri101 significantly reduced inhibitory action of DON on tobacco
plants, there are several conflicting observations regarding the phytotoxicity of
3-acetyldeoxynivalenol (3-ADON) to cereal plants; 3-ADON was reported to be
highly phytotoxic to wheat at low concentrations. To examine whether cereal
plants show sufficient resistance to 3-ADON, we generated transgenic rice plants
with stable expression and inheritance of Tri101. While root growth of wild-type
rice plants was severely inhibited by DON in the medium, this fungal toxin was
not phytotoxic to the transgenic lines that showed trichothecene 3-O-acetylation
activity. This is the first report demonstrating the DON acetylase activity and
DON-resistant phenotype of cereal plants expressing the fungal gene.
PMID- 17031653
TI - Auditory feedback is necessary for long-term maintenance of high-frequency sound
syllables in the song of adult male budgerigars (Melopsittacus undulatus).
AB - Among avian species that communicate using vocalization, songbirds (oscine
Passeriformes), hummingbirds (Trochiliformes), and parrots (Psittaciformes) are
vocal learners. Early studies showed that songbirds require auditory feedback for
song development in young and maintenance in adults. To determine whether
auditory feedback is also necessary for adult song maintenance in non-passerine
species, we deprived adult male budgerigars (Psittaciformes) of auditory input by
surgical cochlear removal. Songs of the deafened birds changed within 6 months
after auditory deprivation. In postoperative songs, high narrowband syllables,
which comprised frequency-modulated narrowband elements with relatively high
fundamental frequencies of 2-4 kHz, decreased significantly. High harmonic
broadband syllables, with fundamental frequencies >/=2 kHz, also decreased. The
altered proportions of syllables were subsequently retained, and maintained 12
months after deafening. The sequence linearity score, a parameter representing
the stereotypy of the syllable sequence, was higher than that before deafening.
The inter-syllable silence was prolonged. Little change was observed in the songs
of intact and sham-operated birds. The significant decrease in high-frequency
syllables and song alteration followed by stabilization resembled the results
with songbirds, although song stabilization took a long time in budgerigars.
Therefore, our results suggest that psittacine budgerigars and oscine songbirds
require auditory feedback similarly for adult song maintenance.
PMID- 17031652
TI - State-of-the-art management of metastatic disease at initial presentation or
recurrence.
AB - Carcinoma of the bladder is the second most prevalent genitourinay malignancy and
the fifth most common solid tumor in the USA. On the basis of favorable response
rates and survival data, cisplatin-based regimens can be considered the standard
treatment for fit patients with metastatic urothelial cancer. Since cisplatin
containing regimens are contraindicated for patients with impaired renal
function, gemcitabine plus either paclitaxel or docetaxel may be an effective and
well-tolerated treatment option for these patients. Randomized trials are needed
to determine the future role of these combinations in the management of advanced
transitional cell carcinoma. The optimal regimens for the medically unfit
patients and second-line chemotherapy remain undefined. Postchemotherapy surgical
resection of residual cancer may result in a disease-free survival in highly
selected patients who would otherwise die of the disease. Progresses in the
understanding of the molecular biology of bladder cancer and identification of
new targeted therapies will undoubtedly provide new opportunities but whether or
not this approach to therapy will lead to better results must still be
determined.
PMID- 17031655
TI - Tau and alpha-synuclein brainstem pathology in Alzheimer disease: relation with
extrapyramidal signs.
AB - Extrapyramidal symptoms (EPS) in Alzheimer disease (AD) often increase with
disease severity. Their neuropathological substrate is a matter of discussion. We
investigated tau and alpha-synuclein (AS) pathologies in brainstem in AD patients
with and without EPS. Among 160 elderly subjects with autopsy-proven AD (110
female, 50 male, aged 61-102, mean 84.1 +/- 8.3 SD years), 151 (94.4%) being
demented, 35 (21.9%) had clinically reported EPS (rigidity, bradykinesia, gait
impairment). Neuropathological examination included standardized classification
of AD according to current criteria, and semiquantitative assessment of neuronal
loss in substantia nigra (SN), locus coeruleus (LC), and of tau and AS lesions in
brainstem, and, in addition, of cerebrovascular lesions. The prevalence of EPS
was only slightly more frequent in higher Braak stages. Tau pathology in
brainstem significantly increased with increasing Braak stages, while AS lesions
did not. EPS correlated best with SN cell loss (P < 0.001) and much less with AS
pathology in several brain areas (P < 0.05), except in medulla oblongata (P <
0.001). Although both pathologies in substantia nigra correlated with neuron loss
(P < 0.001), nigral tau lesions, present in 88.5% of EPS positive cases (without
AS lesions in 55.6%), did not correlate with EPS. Additional cerebrovascular
changes apparently did not influence the development of EPS symptoms in fully
developed AD. With other recent data, these results suggest that neuronal loss in
SN, partly related to tau lesions, is a major pathological substrate of EPS in
AD, but some cases with and without EPS may show no or only minimal nigral
changes. However, often associated with nigral tau lesions and higher Braak
stages, EPS in elderly patients may be a surrogate marker for severe neuritic AD
pathology.
PMID- 17031654
TI - A randomized controlled trial comparing simultaneous intra-operative vs
sequential prophylactic ureteric catheter insertion in re-operative and
complicated colorectal surgery.
AB - OBJECTIVES: Prophylactic insertion of ureteric stents aids intra-operative
identification of ureters and may allow easier visualization of any direct
ureteric injury. Traditionally, ureteric catheters are inserted sequentially,
before starting the abdominal part of the operation. This study determines the
safety and efficacy of simultaneous intra-operative ureteric catheter insertion
during complicated and re-operative colorectal surgery. MATERIALS AND METHODS:
After institutional review board (IRB) approval, 24 patients were randomized into
two groups, sequential (SEQ) and simultaneous (SIM) depending upon the timing of
stent placement relative to abdominal incision. Time taken from induction to
abdominal incision (AIT), induction to peritoneal entry (PET), catheter insertion
time (CIT), and urinary tract infection rates were recorded. Degree of difficulty
for stent insertion was graded on a scale of 1-10. RESULT: Demographics were
similar between groups. Mean AIT (22 +/- 4 vs 41 +/- 7; p = 0.0001) and mean PET
(26 +/- 4.2 vs 44 +/- 7.6; p = 0.0001) were shorter in the SIM group. There was
no significant difference in mean CIT in SIM and SEQ groups (17.9 +/- 4.9 vs 17.6
+/- 5.9 min, p = 0.8). The stents were unsuccessful bilaterally in one patient in
the SEQ group and unilaterally in two other patients, one in each group. The
median difficulty score for catheter insertion was 3 (1-10) and 2 (1-10), (p =
0.12), respectively, in SIM and SEQ groups. There were no ureteric injuries in
either group. One patient in SIM developed a urinary tract infection. CONCLUSION:
Simultaneous ureteric catheter insertion during abdominal procedures reduces
operating times without a significant increase in morbidity. Furthermore, this
permits a policy of selective stent insertion as required by the intra-abdominal
findings after laparotomy.
PMID- 17031656
TI - Genetically distinct astrocytic and oligodendroglial components in
oligoastrocytomas.
AB - Oligoastrocytomas are glial tumours consisting of a mixture of neoplastic
astrocytic and oligodendroglial cells. Genetic alterations of oligoastrocytomas
include loss of heterozygosity of chromosomes 1p and/or 19q (LOH 1p/19q),
typically occurring in oligodendrogliomas, and mutations of TP53, frequently
occurring in astrocytomas. To investigate whether these neoplastic cell types in
oligoastrocytomas have different genetic profiles, we examined the two different
components of oligoastrocytomas in comparison with the histological diagnosis of
the specific tumour area for LOH 1p/19q and TP53 mutations by using
microdissection technique. We found a variety of lost markers for 1p and 19q, and
the presence of two different TP53 mutations in the tumour samples. In the
majority of cases (9/11), the oligodendroglial and astrocytic components of an
individual oligoastrocytoma displayed the same genotype. We present two cases of
biphasic oligoastrocytomas with aberrant findings, suggesting the coexistence of
genetically and morphologically distinct tumour cell clones in these tumours. In
one case, the oligodendroglial part of the tumour showed LOH19q, whereas the
astrocytic part showed TP53 mutation (codon 273). In another case, we found LOH
1p/19q in the oligodendroglial component, but two retained areas on chromosome 1p
in the astrocytic component of the tumour. No evidence was found for the
coexistence of tumour cells with the two genotypical changes within the same
morphological region of one individual tumour. The two cases of biphasic
oligoastrocytomas in our sample that display a different genotype in the
astrocytic and oligodendroglial part of the tumour show that different components
of an oligoastrocytoma may be derived from different cell clones during
neoplastic transformation.
PMID- 17031657
TI - Recombinant human lactoferrin has a potential to suppresses uterine cervical
ripening in preterm delivery in animal model.
AB - OBJECTIVE: To investigate the effect of recombinant human lactoferrin (rhLF) on
cervical ripening using a rabbit model in which preterm labor was induced by
bacterial endotoxin lipopolysaccharide (LPS). STUDY DESIGN: Timed pregnant
rabbits (New Zealand White, 3-4 kg, day 14) were randomly assigned to the
following treatment groups: Group A, LPS + rhLF (n = 4); Group B, LPS (n = 4);
and Group C, control (n = 4). Recombinant human lactoferrin (10 microg) was
administrated to pregnant rabbits in Group A and not in Group B.
Lipopolysaccharide (100 microg) was given to the rabbits in both groups for 3
days (days14-16). Drugs were administered as a vaginal suppository. On day 18,
the rabbits were anesthetized with intramuscular ketamine hydrochloride (20
mg/kg) and diazepam (4 mg/kg). Both cervices of the rabbit uterus, which is
bicorpus-bicolli, were taken out. One cervix was placed in 10% formalin solution
for a histological study with standard hematoxylin-eosin staining. The other was
used for an extension test to assess the grade of ripening. Extension was
measured after a 5-mm length of cervical tissue was loaded with 5.8 g. RESULTS:
The histological study showed remarkably loose and edematous connective tissue in
Group B cervices. Cervical tissues in Group A was not different from those in
Group C. Extension lengths were 2.2 +/- 0.2 mm in Group A, 7.0 +/- 2.7 mm in
Group B, and 1.7 +/- 0.3 mm in Group C. CONCLUSION: These results suggest that
rhLF inhibits cervical maturation induced by LPS in a rabbit model and may have a
potential to prevent preterm delivery caused by cervical infection and ripening.
PMID- 17031658
TI - Bilateral micropapillary serous carcinoma of the ovary: a case report.
AB - BACKGROUND: Micropapillary serous carcinoma (MPSC), a recently described entity
in the group of serous borderline tumor, needs to be recognized and separated
from serous borderline tumor of usual type (SBT) as MPSC has a worse prognosis.
CASE REPORT: We report the case of a 21-year-old female with gradually increasing
lump abdomen for 6 months. Ultrasonography showed bilateral ovarian enlargement
with cysts. Laparotomy revealed both ovaries to be enlarged and right ovary
showed capsular breach. With a per-operative diagnosis of bilateral malignant
ovarian tumor, total abdominal hysterectomy with bilateral salpingo-oophorectomy
was performed. Multiple sections from both ovaries showed non-invasive
micropapillary serous carcinoma with right ovary showing surface growth but no
definite capsular breach. The final histological diagnosis was bilateral
micropapillary serous carcinoma. The patient has been asymptomatic in 10-month
follow-up. CONCLUSION: MPSC, classified as serous borderline tumor, needs to be
differentiated from APST as well as conventional serous carcinoma. It is
diagnosed according to strict criteria laid down. Multiple sections should be
studied to exclude invasion. Adequate peritoneal sampling should be performed to
look for implants, which is of prognostic significance.
PMID- 17031659
TI - Laryngo-tracheal profile: a new method for assessing laryngo-tracheal stenoses.
AB - We present the clinical application of a new method for objective assessment of
both grade and length of laryngo-tracheal stenoses (LTS) on a CT-based
skeletonization algorithm, called laryngo-tracheal profile (LTP). Extraction of
the laryngo-tracheal tract (LTT)-medial axis was performed after S-CT scanning.
Orthogonal to the medial axis, the LTT cross-profile was computed, and the length
and degree of LTS were presented as line charts. Clinical application of this
newly developed method is demonstrated on three patients who had to undergo
preoperative assessment before surgical treatment of tracheal stenoses. LTP
provides an objective method of assessment of both the length and degree of
tracheal stenoses in precise correlation to defined anatomical landmarks. This
method provides important additive information for preoperative evaluation as
well as for monitoring of therapeutical success. Current methods used so far are
able to evaluate the severity of LTS, but do not provide exact quantitative
assessment of complex LTS. Especially in CT-scans of strong curved passages,
where an overestimation of the cross-sectional area results by an oblique cut of
the tubular structure, LTP may overcome this problem by a simple post processing
skeletonization algorithm.
PMID- 17031660
TI - Fast alterations of vascular endothelial growth factor (VEGF) expression and that
of its receptors (Flt-1, Flk-1 and Neuropilin) in the cochlea of guinea pigs
after moderate noise exposure.
AB - Vascular endothelial growth factor (VEGF) is a vascular permeability regulating,
proangiogenic factor with neuroprotective properties. Its expression in the inner
ear has been demonstrated, but little is known concerning its subcellular
distribution or potential involvement in sound perception and adaptation to
noise. Therefore, we determined the expression patterns and levels of VEGF and
the three VEGF-receptors FLK, FLT and Neuropilin in the cochlea of guinea pigs,
and examined the alterations occurring after noise exposure. After 70 dB
exposure, VEGF expression was found to be reduced in all cell types of the organ
of Corti, in the stria vascularis and in spiral ganglion cells. Additional down
regulation was observed in the spiral ligament and in interdental cells after 90
dB. In contrast, VEGF showed an in tendency increased level after both
intensities in nerve fibers of the osseous spiral lamina. Expression of FLT was
affected similarly, showing down-regulation after 70 and 90 dB on spiral ganglion
cells, the nerve fibers of the osseous spiral lamina and on Deiters cells.
Additionally, down-regulation was observed in the remaining cell types of the
organ of Corti, the stria vascularis, the spiral ligament and the interdental
cells. The Neuropilin levels remained unchanged by our experiments; apart from
the blood vessel endothelium, there was no detectable expression in any of the
cell types investigated. The FLK expression pattern was likewise unaffected by
exposure to 70 or 90 dB, with the notable exception of an increased level
occurring in Schwann cells after 90 dB. We postulate that modulation of VEGF and
its receptors may be part of a neuroprotective mechanism in response to noise.
PMID- 17031661
TI - Cytogenetic effects of low-dose radiation with different LET in human peripheral
blood lymphocytes.
AB - Chromosome damage and the spectrum of aberrations induced by low doses of gamma
irradiation, X-rays and accelerated carbon ions (195 MeV/u, LET 16.6 keV/microm)
in peripheral blood lymphocytes of four donors were studied. G0-lymphocytes were
exposed to 1-100 cGy, stimulated by PHA, and analyzed for chromosome aberrations
at 48 h post-irradiation by the metaphase method. A complex nonlinear dose-effect
dependence was observed over the range of 1 to 50 cGy. At 1-7 cGy, the cells
showed the highest radiosensitivity per unit dose (hypersensitivity, HRS), which
was mainly due to chromatid-type aberration. According to the classical theory of
aberration formation, chromatid-type aberrations should not be induced by
irradiation of unstimulated lymphocytes. With increasing dose, the frequency of
aberrations decreased significantly, and in some cases it even reached the
control level. At above 50 cGy the dose-effect curves became linear. In this dose
range, the frequency of chromatid aberrations remained at a low constant level,
while the chromosome-type aberrations increased linearly with dose. The high
yield of chromatid-type aberrations observed in our experiments at low doses
confirms the idea that the molecular mechanisms which underlie the HRS phenotype
may differ from the classical mechanisms of radiation-induced aberration
formation. The data presented, as well as recent literature data on bystander
effects and genetic instability expressed as chromatid-type aberrations on a
chromosomal level, are discussed with respect to possible common mechanisms
underlying all low-dose phenomena.
PMID- 17031662
TI - The use of a syncytium model of the crystalline lens of the eye as a new tool to
study the light flashes phenomenon seen by astronauts.
AB - A syncytium model to study some electrical properties of the eye is proposed to
study the phenomenon of anomalous light flashes (LF) perceived by astronauts in
orbit. The crystalline lens is modelled as an ellipsoidal syncytium with a
variable relative dielectric constant. The corresponding mathematical model is a
boundary value problem for a system of two coupled elliptic partial differential
equations in the two unknown syncytial electrical potentials. A numerical method
to compute an approximate solution of this mathematical model is used, and some
numerical results are shown. The model can be regarded as a new tool to study the
LF phenomenon. In particular, the energy lost in the syncytium by a transversing
cosmic charged particle is calculated and the results obtained with the syncytium
model are compared with those obtained using the previously available Geant 3.21
simulation program. In addition, the interaction of antimatter-syncytium is
studied, and the Creme96 computer program is used to evaluate the cosmic ray
fluxes encountered by the International Space Station in its standard mission.
PMID- 17031663
TI - The role of SUMO in chromosome segregation.
AB - Chromosome segregation is an essential feature of the eukaryotic cell cycle.
Efficient chromosome segregation requires the co-ordination of several cellular
processes; some of which involve gross rearrangements of the overall structure of
the genetic material. Recent advances in the analysis of the role of SUMO (small
ubiquitin-like modifier) and in the identification of SUMO-modified targets
indicate that sumoylation is likely to have several key roles in regulating
chromosome segregation This mini-review summarises the recently published data
concerning the role of SUMO in the processes required for efficient chromosome
segregation.
PMID- 17031664
TI - Kinematic invariants during cyclical arm movements.
AB - It has been observed that the motion of the arm end-point (the hand, fingertip or
the tip of a pen) is characterized by a number of regularities (kinematic
invariants). Trajectory is usually straight, and the velocity profile has a bell
shape during point-to-point movements. During drawing movements, a two-thirds
power law predicts the dependence of the end-point velocity on the trajectory
curvature. Although various principles of movement organization have been
discussed as possible origins of these kinematic invariants, the nature of these
movement trajectory characteristics remains an open question. A kinematic model
of cyclical arm movements derived in the present study analytically demonstrates
that all three kinematic invariants can be predicted from a two-joint
approximation of the kinematic structure of the arm and from sinusoidal joint
motions. With this approach, explicit expressions for two kinematic invariants,
the two-thirds power law during drawing movements and the velocity profile during
point-to-point movements are obtained as functions of arm segment lengths and
joint motion parameters. Additionally, less recognized kinematic invariants are
also derived from the model. The obtained analytical expressions are further
validated with experimental data. The high accuracy of the predictions confirms
practical utility of the model, showing that the model is relevant to human
performance over a wide range of movements. The results create a basis for the
consolidation of various existing interpretations of kinematic invariants. In
particular, optimal control is discussed as a plausible source of invariant
characteristics of joint motions and movement trajectories.
PMID- 17031665
TI - Patch pipettes are more useful than initially thought: simultaneous pre- and
postsynaptic recording from mammalian CNS synapses in vitro and in vivo.
PMID- 17031666
TI - Evidence that TRPC4 supports the calcium selective I(CRAC)-like current in human
gingival keratinocytes.
AB - We previously demonstrated that high external [Ca(2+)] activated two Ca(2+)
currents in human gingival keratinocytes (HGKs): an initial small I(CRAC)-like
current and a second large nonspecific cation current (Fatherazi S, Belton CM,
Cai S, Zarif S, Goodwin PC, Lamont RJ, Izutsu KT; Pflugers Arch 448:93-104,
2004). It was recently shown that TRPC1, a member of the transient receptor
potential protein family, is a component of the store-operated calcium entry
mechanism in keratinocytes. To further elucidate the molecular identity of these
channels, we investigated the expression of TRPC4 in gingival tissue and in
cultured keratinocytes, and the effect of knockdown of TRPC4 expression on the
Ca(2+) currents and influx. Immunohistochemistry showed TRPC4 was present in
gingival epithelium as well as in HGKs cultured in different [Ca(2+)]s. Results
from tissue and cultured HGKs demonstrated TRPC4 expression decreased with
differentiation. Knockdown of TRPC4 in proliferating HGKs with antisense
oligonucleotides significantly reduced the intracellular [Ca(2+)] increase
obtained upon exposure to high external [Ca(2+)]. Antisense knockdown of TRPC4
expression was confirmed by reverse transcriptase polymerase chain reaction,
Western blot, and immunofluorescence microscopy of transfected HGKs.
Immunofluorescence microscopy and patch clamp measurements in Lucifer-yellow
tagged, antisense-treated HGKs showed attenuation of TRPC4 expression levels as
well as attenuation of the I(CRAC)-like current in the same cell, whereas the
large nonspecific cation current was unchanged but significantly delayed. Cells
transfected with a scrambled TRPC4 oligonucleotide showed no change in either the
I(CRAC)-like or nonspecific currents. The results indicate that TRPC4 is an
important component of the I(CRAC)-like channel in HGKs.
PMID- 17031668
TI - High extracellular K(+) evokes changes in voltage-dependent K(+) and Na (+)
currents and volume regulation in astrocytes.
AB - [K(+)](e) increase accompanies many pathological states in the CNS and evokes
changes in astrocyte morphology and glial fibrillary acidic protein expression,
leading to astrogliosis. Changes in the electrophysiological properties and
volume regulation of astrocytes during the early stages of astrocytic activation
were studied using the patch-clamp technique in spinal cords from 10-day-old rats
after incubation in 50 mM K(+). In complex astrocytes, incubation in high K(+)
caused depolarization, an input resistance increase, a decrease in membrane
capacitance, and an increase in the current densities (CDs) of voltage-dependent
K(+) and Na(+) currents. In passive astrocytes, the reversal potential shifted to
more positive values and CDs decreased. No changes were observed in astrocyte
precursors. Under hypotonic stress, astrocytes in spinal cords pre-exposed to
high K(+) revealed a decreased K(+) accumulation around the cell membrane after a
depolarizing prepulse, suggesting altered volume regulation. 3D confocal
morphometry and the direct visualization of astrocytes in enhanced green
fluorescent protein/glial fibrillary acidic protein mice showed a smaller degree
of cell swelling in spinal cords pre-exposed to high K(+) compared to controls.
We conclude that exposure to high K(+), an early event leading to astrogliosis,
caused not only morphological changes in astrocytes but also changes in their
membrane properties and cell volume regulation.
PMID- 17031669
TI - Embryonic expression of HeFoxA1 and HeFoxA2 in an indirectly developing
polychaete.
AB - Two forkhead family transcription factors, HeFoxA1 and HeFoxA2, were isolated
from the serpulid annelid Hydroides elegans and their transcript distribution
were characterized during embryogenesis. HeFoxA1 is first detected in second
quartet blastomeres soon after their formation, and later in all vegetal half
blastomeres, which comprise ectoderm, endoderm, and mesoderm precursors. HeFoxA1
expression declines first in subtrochal ectoderm and presumptive midgut
precursors, as well as apparently in D quadrant blastomeres in advance of any
known signaling events. Later, during gastrulation, HeFoxA1 declines in hindgut
precursors, and by the end of gastrulation the expression remains active only in
foregut precursors. HeFoxA1 is apparently expressed in ectomesoderm cells
involved in forming the larva-specific protonephridium (the so-called head
kidney). The other ortholog, HeFoxA2, is expressed in a subset of the cells in
which HeFoxA1 is expressed during early stages, but later it is largely
restricted to the endoderm-ectoderm boundary of the proctodaeum. In addition,
HeFoxA2 has a unique expression in two hindgut cells and abutting ectoderm cells
located by the imminent anal opening. The combined expression of HeFoxA1 and
HeFoxA2 correlates with mesoderm and endoderm expression of their orthologs in
other bilaterians.
PMID- 17031667
TI - Regulation of TRP channels by PIP(2).
AB - Transient receptor potential (TRP) channels are regulated by a wide variety of
physical and chemical factors. Recently, several members of the TRP channel
family were reported to be regulated by phosphatidylinositol 4,5-bisphosphate
(PtdIns(4,5)P(2), PIP(2)). This review will summarize the current knowledge on
PIP(2) regulation of TRP channels and discuss the possibility that PIP(2) is a
common regulator of mammalian TRP channels.
PMID- 17031670
TI - Human xenograft osteosarcoma models with spontaneous metastasis in mice: clinical
relevance and applicability for drug testing.
AB - Osteosarcoma cells derived from patients have been isolated and subsequently
cultured for the past 35 years. To date though, there have been no major
breakthroughs in the development of a model for osteosarcoma that uses orthotopic
implantation of human osteosarcoma cells and that closely emulates the clinical
progression of this debilitating and fatal disease. Such a model is long overdue
given the devastating demographics (second highest cause of cancer-related death
in the paediatric age group) of the ailment and the lack of solid options for
control, if not cure, for the disease, as it also is the most common primary
tumour of bone. Only then can more robust R & D be undertaken in the search for
efficacious anti-osteosarcoma agents. This review tackles this conundrum and
lists the variety of models (that use human osteosarcoma cells) available and the
types of studies performed with these.
PMID- 17031671
TI - Roles of EGFR-Stat3 signal pathway in carcinogenesis of experimental hepatoma in
rats.
AB - The purpose of this study is to investigate if the EGFR-Stat3 signal pathway
contributes to the carcinogenesis of hepatoma in rats. Hepatoma was induced in
rats by 3'Me-DAB as a model. EGFR, TGFalpha, Stat3, p-Stat3 in different stages
of carcinogenesis were detected by immunohistochemistry and Western blot. In situ
hybridization was applied to investigate the expression of Stat3 mRNA. The
expressions of signal molecules were assessed by KS400 Image Analysis system. The
data were statistically evaluated. EGFR, TGFalpha, Stat3 were highly expressed in
the stages of liver necrosis and repairment. All hepatocellular carcinoma cases
revealed elevated expression of EGFR, TGFalpha. Elevation of Stat3 mRNA and
protein levels were identified, increase of activation of Stat3 was also
observed. In HCC, there was positive correlation between p-Stat3 level and the
expression of TGFalpha and PCNA. Increased expression of Bcl-2 (P < 0.05)
coincided with elevated level of p-Stat3. Therefore, the EGFR-Stat3 signal
pathway was related to the development of hepatoma in rats. TGFalpha-EGFR
autocrine ring formation may lead to the activation of Stat3 and in turn, promote
proliferation and regulate the transcription of genes regulating cell apoptosis
and cell cycle.
PMID- 17031672
TI - Assessment of formal and low structured kinetic modeling of polyhydroxyalkanoate
synthesis from complex substrates.
AB - A formal kinetic mathematical model for poly-(3-hydroxybutyrate-co-3
hydroxyvalerate-co-4-hydroxybutyrate) [P(3HB-co-3HV-co-4HB)] terpolyester
synthesis from glucose and galactose derived from whey permeate supplemented with
gamma-butyrolactone by the archaeon Haloferax mediterranei was created. Further,
a low structured mathematical model for poly-3-hydroxybutyrate synthesis from
whey permeate by Pseudomonas hydrogenovora was developed. In both cases,
biosyntheses for obtaining the experimental data used for compiling the models
were performed via fed-batch cultivations. The model developed for H.
mediterranei consists of 10 differential and 11 algebraic equations, including 27
kinetic constants. The model compiled for P. hydrogenovora encompasses 10
differential and 3 algebraic equations, including 36 kinetic constants. Both
models were solved by Runge-Kuta variable step numerical integration with Monte
Carlo parameter optimization procedure. Difficulties arising from the modeling of
redirection of metabolic fluxes from biomass growth toward polyhydroxyalkanoate
synthesis and byproducts are discussed.
PMID- 17031673
TI - Proximal direct composite restorations and chairside CAD/CAM inlays: marginal
adaptation of a two-step self-etch adhesive with and without selective enamel
conditioning.
AB - The aim of this study was to evaluate the marginal adaptation of CEREC ceramic
inlays, CEREC composite inlays and direct composite restorations in unbeveled
proximal slot cavities under artificial aging conditions. Two groups of each
restoration type were prepared (n = 6), one group with a self-etch adhesive, the
other group with H(3)PO(4) enamel etching before the self-etch adhesive
application. Replicas were generated before and after long-term thermo-mechanical
loading under dentinal fluid simulation and margins were evaluated at x200
magnification in the scanning electron miscroscope (SEM). Statistically,
significant differences were found before and after loading with respect to the
percentages of "continuous margins", the direct composite filling with H(3)PO(4)
enamel etching giving the lowest percentages of "continuous margins" after
loading (p < 0.05). The highest percentage of "continuous margin" was attained by
composite inlays without H(3)PO(4) enamel etching. However, these results were
not significantly different from ceramic inlays after stressing. Polymerization
shrinkage is still one critical property of composite restorative materials. The
marginal adaptation of indirect adhesive proximal slot restorations without
enamel bevels both fabricated out of composite and ceramic is better than that of
directly placed composite restorations.
PMID- 17031674
TI - Micronucleus--an upcoming marker of genotoxic damage.
AB - This study was conceived for the early detection of oral precancer and cancer
lesions using a noninvasive reliable technique. Micronucleus assay was performed
on oral exfoliated cells of chosen subjects having leukoplakia and squamous cell
carcinoma (SCC) using fluorescent (Acridine Orange) and conventional (Feulgen)
stainings. The results were analyzed using Mann-Whitney U test, Kruskal-Wallis
test, Spearman's Correlation and SPSS statistical package. The frequency of mean
percentage occurrence of micronucleated cells increased significantly in
comparison to controls with leukoplakia and squamous cell carcinoma. Subjects
with synergism of abnormal oral habits also showed increased micronucleated
cells. Fluorescent staining was found to be more sensitive than the conventional
one for micronucleus detection. The results clearly demonstrate that micronucleus
assay in oral exfoliated cells can be used as a simple reliable marker to assess
the genotoxicity and for the early diagnosis of premalignant and malignant
lesions. Micronucleus assay is, thus, an easy tool for early detection of cancer.
PMID- 17031675
TI - [Ulceration of the hard palate in a 50-year-old patient].
PMID- 17031676
TI - [Special ginkgo extract in cases of vertigo: a systematic review of randomised,
double-blind, placebo controlled clinical examinations].
AB - BACKGROUND: The concept for the medical treatment of vertigo has changed over the
last 30 years due to recognition of the dependence of the vertiginous sensation
on vestibular compensation and the dependence of vestibular compensation on the
state of vigilance. METHODS: In this systematic review, experimental studies of
the influence of the special ginkgo extract EGb 761 on vestibular compensation in
animals and randomized, double-blind clinical studies of EGb 761 in vestibular
and non-vestibular vertigo are described and critically evaluated. RESULTS: The
beneficial effect of EGb 761 on vestibular compensation has been demonstrated in
preclinical and clinical studies. CONCLUSION: Evidence of the efficacy of EGb 761
for the treatment of vertiginous syndromes is presented in the available studies.
PMID- 17031677
TI - [Differential diagnosis of chronic synovitis].
AB - This review presents an algorithm for the standardised histopathological
diagnostics of synovial biopsies and synovectomy specimens. In general, changes
of the synovium can be inflammatory or non-inflammatory. To the latter group
belong certain benign tumors such as the diffuse variant of the tenosynovial
giant cell tumor, lipoma or synovial chondromatosis, additionally the rare group
of storage diseases should be kept in mind. Inflammatory diseases can be
discriminated into crystal-induced arthropathies such as gout and pseudogout,
into granulomatous diseases such as tuberculosis, sarcoidosis and foreign-body
inoculation, and into the large group of non-granulomatous synovitis. This group
is by far the most common, and it often causes difficulties in assigning the
histopathological findings to a concrete diagnosis. Therefore, the synovitis
score should be applied as a diagnostic device in these cases, leading to the
diagnosis of a low-grade synovitis (which is associated with degenerative
arthropathies) or of a high-grade synovitis (associated with rheumatic diseases),
the sensitivity and specificity being 60.5% and 95.5%, respectively.
PMID- 17031678
TI - A novel deletion in the GJA12 gene causes Pelizaeus-Merzbacher-like disease.
AB - Pelizaeus-Merzbacher disease (PMD) and Pelizaeus-Merzbacher-like disease (PMLD)
are hypomyelinating disorders of the central nervous system with a very similar
phenotype. PMD is an X-linked disorder caused by mutations in PLP1. PMLD is an
autosomal recessive condition caused by mutations in GJA12. We report a 5-year
old girl with a complex neurological syndrome and severe hypomyelination on brain
magnetic resonance imaging. She harbored a homozygous 34-bp deletion in the
coding region of GJA12. There are no distinctive features for the differential
diagnosis of PMD/PMLD. GJA12 should be analyzed in all patients without PLP1
mutations but should also be considered the initial genetic test in women and in
patients with consanguineous parents.
PMID- 17031679
TI - De novo double mutation in PAX6 and mtDNA tRNA(Lys) associated with atypical
aniridia and mitochondrial disease.
AB - We report on the clinical, molecular and biochemical findings of a patient with
the rare event (<4.02 x 10(-9) per generation) of coinciding de novo mutations in
the nuclear PAX6 (c.1252-1267del16) and the mitochondrial mt.RNA (Lys) (8347A-
>G) genes. The boy suffers from exercise intolerance, ptosis, nystagmus, macular
hypoplasia and anterior segment abnormalities evocative of Axenfeld-Rieger
anomaly. The PAX6 mutation is predicted to cause haploinsufficiency. The novel
mt.RNA (Lys) mutation is located close to the classic myoclonic epilepsy with
ragged-red-fibers mutation, but the patient exhibits neither myoclonic epilepsy
nor ragged-red-fibers. The degree of mutant mtDNA heteroplasmy, as determined by
a very accurate pyrosequencing assay, varies between 31% (muscle) and 38%
(fibroblasts). We discuss a potential effect of the PAX6 mutation on the mtDNA
mutation rate.
PMID- 17031680
TI - Regulation of metal transporters by dietary iron, and the relationship between
body iron levels and cadmium uptake.
AB - Iron (Fe) plays essential roles in biological processes, whereas cadmium (Cd) is
a toxic and non-essential metal. Two metal transporters, divalent metal
transporter 1 (DMT1) and metal transporter protein 1 (MTP1), are responsible for
Fe transport in mammals. Here, we studied the effect of dietary Fe on the
expression of these metal transporters in peripheral tissues, and the uptake by
these tissues of Cd. Mice were fed an Fe-sufficient (FeS: 120 mg Fe/kg) or Fe
deficient (FeD: 2-6 mg Fe/kg) diet for 4 weeks. The total Fe levels in the body
were evaluated by measuring tissue Fe concentrations. Tissue Cd concentrations
were determined 24 h after the mice received a single oral dose of Cd. Animals
fed a FeD diet showed depletion of body Fe levels and accumulated 2.8-fold higher
levels of Cd than the FeS group. Quantitative real time RT-PCR revealed that
whereas DMT1 and MTP1 were both ubiquitously expressed in all FeS peripheral
tissues studied, DMT1 was highly expressed in brain, kidney, and testis, whereas
MTP1 was highly expressed in liver and spleen. Depletion of the body Fe stores
dramatically upregulated DMT1 and MTP1 mRNA expression in the duodenum as well as
moderately upregulating their expression in several other peripheral tissues. The
iron response element positive isoform of DMT1 was the most prominently
upregulated isoform in the duodenum. Thus, DMT1 and MTP1 may play an important
role in not only maintaining Fe levels but also facilitating the accumulation of
Cd in the body of mammals.
PMID- 17031681
TI - Human standing and walking: comparison of the effects of stimulation of the
vestibular system.
AB - The adoption of bipedalism by hominids including man has complicated the tasks of
balance control and the minimisation of body sway. We have investigated the role
of the vestibular organs in controlling sway in the roll direction using galvanic
vestibular stimulation (GVS). Two stance conditions were studied: during forward
lean posterior compartment muscles are activated and during backward lean
anterior compartment muscles are activated. GVS-evoked vestibular signals in
stance control leg muscles as a group: all the active muscles in the leg on the
GVS cathode side are excited together and those in the contralateral leg (anode
side) relax. The subject sways towards the anode side. During treadmill walking,
vestibular actions are subtly different: the actions are largely restricted to
muscles acting at the ankle joint, occur at longer latencies, are not reciprocal
in the opposite limb, are modulated throughout the step cycle (largest early in
stance) and are reversed in sign in the peroneus longus muscle. The subject
deviates towards the anode side. Hand contact with a firm object reduces GVS
evoked responses in leg muscles during treadmill walking. Responses to GVS are
observed during over-ground walking but not significantly during bicycling on an
ergometer. The observations suggest that these vestibular actions are part of a
roll stabilisation mechanism. They may be mediated through different spinal
premotor mechanisms during standing and walking and turned off during bicycling,
when leg muscles have no balance control function.
PMID- 17031683
TI - Virtual time-to-contact of postural stability boundaries as a function of support
surface compliance.
AB - This study investigated the hypothesis that virtual time-to-contact, which
specifies the time to reach the functional stability boundary, is a variable
controlled in the maintenance of upright posture. Three different levels of
support surface compliance were used on a force platform (no foam, 5 cm of foam,
and 15 cm of foam). The participant's task was to stand still under each surface
support condition both with and without vision. The stability boundary was
determined for each set of conditions where the participant was required to lean
as far as possible in all directions of the horizontal plane without losing
stability. The results showed that the no vision conditions had a significantly
larger center of pressure displacement than the vision conditions. No vision and
increasing support surface compliance also increased the velocity of the center
of pressure trajectory. The distribution of the radial displacement of the center
of pressure showed relatively equal frequency over spatial location with no
central tendency. The virtual time-to-contact with the stability boundary
decreased as platform surface support became more compliant. Furthermore, the
distribution of virtual time over the effective scaling range was a power law
with a larger exponent in the more unstable no vision and increasing surface foam
conditions. The findings provide additional evidence for the hypothesis that
virtual time-to-contact with stability boundaries is a postural control variable
that is regulated rather than the preservation of minimal motion around the
center of the stability region as proposed in pendulum models of posture.
PMID- 17031682
TI - Forces applied by anterior and posterior teeth and roles of periodontal afferents
during hold-and-split tasks in human subjects.
AB - Hold-and-split tasks were performed by 20 subjects (12 females and 8 males) using
the right central incisors, canines, 2nd premolars, and 1st molars, respectively.
Half a peanut was positioned on a transducer-equipped plate and the subject was
instructed to hold the plate with the peanut between two antagonistic teeth, and
not using more force than necessary. After ca. 3 s the subject was instructed to
split the peanut in a natural manner. Each session consisted of a series of three
in which the subject performed the hold-and-split task five times for each tooth.
Thus, in total, data were obtained from 60 trials for each subject. The magnitude
of the forces and the force rates used to split the peanut increased distally
along the dental arch. However, the duration of the split phase was similar for
the various teeth examined. During anesthesia of the periodontal ligament (four
subjects), no significant changes were seen in the split phase. The forces used
to hold the peanut between the teeth also increased distally along the dental
arch: 0.60 N for the incisor, 0.77 N for the canine, 1.15 N for the 2nd premolar,
and 1.74 N for the 1st molar. The difference in hold forces for the various teeth
can be explained by the different sensitivity characteristics of the periodontal
afferents innervating anterior and posterior teeth. During periodontal
anesthesia, the magnitude and variability of the hold forces increased for all
types of teeth, thus supporting the suggestion that periodontal afferent
information is used in the regulation of the level of forces used to hold and
manipulate morsels between the teeth.
PMID- 17031684
TI - Inflammation of Hoffa's fat pad in the setting of HIV: magnetic resonance imaging
findings in six patients.
AB - OBJECTIVE: To describe MR imaging findings of inflammation of Hoffa's fat pad as
a cause of nonspecific knee pain in the HIV-infected population. DESIGN:
Retrospective review. PATIENTS: A retrospective review of 400 consecutive MR
imaging studies of the knee performed at two institutions over a six-month period
was conducted. Inclusion criteria included HIV infection in conjunction with
diffuse high signal intensity throughout Hoffa's fat pad on fluid sensitive
sequences. Medical histories and images were reviewed by two musculoskeletal
radiologists. Exclusion criteria included post-surgical changes, internal
derangement, and/or changes consistent with an active synovial inflammatory
process. RESULTS: Seven HIV-infected subjects with non-specific knee pain were
identified, six of whom met imaging inclusion criteria. Findings in Hoffa's fat
pad were present in nine MR studies (bilateral in three, and unilateral in three
subjects). Other findings include bilateral enlargement of Hoffa's fat pad in one
subject, global increase in signal intensity of the suprapatellar fat pad on
fluid sensitive sequences in three subjects and of the prefemoral fat pad in four
subjects, avascular necrosis in one subject, and a diffuse pattern of patchy bone
marrow edema in one subject. Subjects were diagnosed with HIV from 1993-1999,
with imaging performed in 2005. Subjects were on HAART medication for an
indeterminate, extended duration of time prior to imaging. CD4 levels of subjects
ranged from 448-1262 cells/muL (X=727.33 cells/muL). CONCLUSIONS: While the MR
imaging findings of diffuse inflammation of Hoffa's fat pad are nonspecific and
unclear in etiology, an association with HIV may exist.
PMID- 17031685
TI - Severe infectious complications in a patient treated with rituximab for
idiopathic thrombocytopenic purpura.
PMID- 17031686
TI - Seizures as an adverse drug reaction after therapeutic dose of vincristine.
PMID- 17031688
TI - Thrombotic thrombocytopenic purpura as the initial presentation of Pneumocystis
jiroveci pneumonia in an immunocompetent patient.
PMID- 17031687
TI - Syndrome of inappropriate secretion of ADH after administration of intrathecal
chemotherapy in acute promyelocytic leukemia with empty sella of pituitary gland.
PMID- 17031689
TI - Higher fungal infection rate in elderly patients (more than 80 years old)
suffering from diffuse large B cell lymphoma and treated with rituximab plus
CHOP.
AB - Although adding rituximab to standard cyclophosphamide, doxorubicin, vincristine,
and prednisone (CHOP) chemotherapy is an efficacious and well-tolerated regimen
in elderly patients with diffuse large B cell lymphoma (DLBCL), it may increase
susceptibility to opportunistic infections, and such cases have been reported.
Our study was to identify the risk factors for fungal infection in a
retrospective case-control matched study of 34 elderly DLBCL patients treated
with rituximab plus CHOP (R-CHOP) and 35 control patients treated with the
standard CHOP regimen at the Taipei Veterans General Hospital, Taiwan. The rate
of overall infection was similar in both groups. However, subgroup analysis found
that the fungal infection rate was significantly different, 41.7 and 17.1%, in
the R-CHOP and CHOP groups, respectively, (P = 0.03). Univariate analysis
identified the rituximab plus CHOP chemotherapy regimen (P = 0.03), age older
than 80 years (P = 0.04), and bone marrow involvement (P = 0.04) as risk factors
for development of fungal infection, whereas, multivariate regression analysis
identified only rituximab plus CHOP and old age. Adding rituximab to the standard
CHOP regimen in elderly DLBCL patients might increase the incidence of fungal
infection especially in those older than 80 years old.
PMID- 17031690
TI - High-vs low-dose cytarabine combined with interferon alfa in patients with first
chronic phase chronic myeloid leukemia. A prospective randomized phase III study.
AB - A prospective randomized phase III study was performed to evaluate whether
intensified cytarabine would induce a higher response rate and longer event-free
interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML).
One hundred and eighteen patients with CML in early chronic phase entered the
study. Twenty-eight out of 32 patients assigned to group A received two cycles of
a combination of intensified cytarabine and idarubicin followed by interferon
alfa (IFN-alpha) maintenance, 28 patients in group B received standard treatment
by a combination of low-dose cytarabine and IFN-alpha. Forty-nine patients with a
human leukocyte antigen-identical sibling donor proceeded to allogeneic stem cell
transplantation (allo-SCT) and nine patients were excluded from the analysis.
Hematological response was observed in 97% of the patients in group A vs 86% of
the patients in group B during the first year of treatment. In group A, 16
patients (50%) achieved a major cytogenetic response, which compared to seven
patients (25%) with a major cytogenetic response in group B. With a median follow
up of 58 months (range 34-76), event-free survival was not significantly
different between arms A and B. The estimated 5-year survival rate was 56% in the
intensified arm and 77% in the low-dose arm (P = 0.05). Recipients of allo-SCT
showed a 5-year estimated survival rate of 55%. Although intensified cytarabine
induced a higher initial percentage of major and complete cytogenetic responses,
responses were not sustained by IFN-alpha maintenance therapy.
PMID- 17031691
TI - Effect of L-carnitine on the physical fitness of thalassemic patients.
AB - Poor physical fitness is a common problem among thalassemic patients. L-Carnitine
plays an essential role in fatty acid beta-oxidation, a process especially
important in the organs that preferentially use fatty acid as a source of energy
such as the myocardium and the skeletal muscles. The main objective of this study
is to assess the effect of the administration of oral L-carnitine on exercise
tolerance and physical fitness in patients with thalassemia major. Thirty
patients followed up at the New Cairo University Children Hospital were included
in this study. Clinical, laboratory, and cardiopulmonary exercise testing were
performed before and after 6 months of oral L-carnitine therapy (50 mg/kg/day).
The oxygen consumption, cardiac output, and oxygen pulse at maximal exercise
significantly increased after L-carnitine therapy (p<0.001, p=0.002 and p<0.001,
respectively). However, there was no significant change in minute ventilation and
ventilatory equivalent of carbon dioxide (p=0.07 and p=0.06, respectively). A
weak but positive correlation between the age of the patients and the degree of
improvement in exercise parameters was noted. There was also significant increase
in the blood transfusion intervals after L-carnitine administration (p=0.008).
However, there was no significant change in hemoglobin concentration (p=0.4). L
Carnitine seems to be a safe and effective adjunctive therapeutic approach in
thalassemic patients. It improves their cardiac performance and physical fitness.
The younger the patients are, the higher is the degree of improvement in their
exercise parameters.
PMID- 17031692
TI - Hypoxic changes in Purkinje cells of the human cerebellum.
AB - The significance of both Purkinje cell numbers and various neuronal changes for
the diagnosis and timing of hypoxic-induced brain lesions was investigated in
tissue samples from the cerebellar cortex of 52 individuals with a history of
acute or prolonged cerebral hypoxia/ischemia before death. Furthermore, the area
of the Purkinje cell somata (PC size) was measured using an automatic image
processing and analysis system (LEICA QWin). Significantly reduced numbers of
Purkinje cells (<6 cells/unit length of 1 mm) and a decreased portion (<50%) of
intact Purkinje cells could be detected in individuals with a period of
resuscitation of at least 2 h after acute circulatory arrest. Average cell
numbers of less than 4 cells/unit were found in individuals who suffered from
diffuse brain swelling and were ventilated for at least 3 days, as well as in
individuals who died of brain death. Moreover, the Purkinje cells in these cases
exhibited shrunken somata compared to the controls. Specimens that were stored at
room temperature up to 30 h after removal at autopsy showed no significant
autolytic changes of the Purkinje cells. After 46 h, however, reduced Purkinje
cell numbers and shrunken cell bodies were found.
PMID- 17031693
TI - Changes in markers of muscle damage, inflammation and HSP70 after an Ironman
Triathlon race.
AB - We investigated the effects of an Ironman triathlon race on markers of muscle
damage, inflammation and heat shock protein 70 (HSP70). Nine well-trained male
triathletes (mean +/- SD age 34 +/- 5 years; VO(2peak) 66.4 ml kg(-1) min(-1))
participated in the 2004 Western Australia Ironman triathlon race (3.8 km swim,
180 km cycle, 42.2 km run). We assessed jump height, muscle strength and
soreness, and collected venous blood samples 2 days before the race, within 30
min and 14-20 h after the race. Plasma samples were analysed for muscle proteins,
acute phase proteins, cytokines, heat shock protein 70 (HSP70), and clinical
biochemical variables related to dehydration, haemolysis, liver and renal
functions. Muscular strength and jump height decreased significantly (P < 0.05)
after the race, whereas muscle soreness and the plasma concentrations of muscle
proteins increased. The cytokines interleukin (IL)-1 receptor antagonist, IL-6
and IL-10, and HSP70 increased markedly after the race, while IL-12p40 and
granulocyte colony-stimulating factor (G-CSF) were also elevated. IL-4, IL-1beta
and tumour necrosis factor-alpha did not change significantly, despite elevated C
reactive protein and serum amyloid protein A on the day after the race. Plasma
creatinine, uric acid and total bilirubin concentrations and gamma-glutamyl
transferase activity also changed after the race. In conclusion, despite evidence
of muscle damage and an acute phase response after the race, the pro-inflammatory
cytokine response was minimal and anti-inflammatory cytokines were induced. HSP70
is released into the circulation as a function of exercise duration.
PMID- 17031694
TI - Navigating laparoscopic surgery into the next decade in developing countries - a
personal perspective.
AB - INTRODUCTION: Over 500 years ago, Vasco de Gama navigated from west to east, from
Lisbon in Portugal to Calicut in India, in an epic voyage that lasted over 1 year
(Fig. 1). This voyage was perhaps the greatest historic and, certainly, the
greatest navigational achievement of the last millennium. For better or for
worse, it catalysed a series of events that forever changed not only the history,
but also the geography of the world. DISCUSSION: In our plans to navigate
endoscopic surgery into the next decade in developing countries, we too should
endeavour to change both the history and the geography of surgery. This talk
traces a journey over 34 years of effort to spread laparoscopic surgery into
developing countries.
PMID- 17031695
TI - The effect of NG-nitro L-arginine methyl ester on colonic anastomosis after
increased intra-abdominal pressure.
AB - BACKGROUND: Intestinal ischemia-reperfusion (I/R) is associated with augmented
nitric oxide (NO) production. Increased intra-abdominal pressure (IAP) during
surgical pneumoperitoneum (P) facilitates I/R injury. We previously demonstrated
decreased strength and healing of colocolic anastomoses after high IAPs. The
effect of an NO synthase inhibitor, N (G)-nitro-arginine methyl ester (L: -NAME),
on anastomoses realized in colonic tissue exposed to high IAPs was investigated
in this study, a randomized, controlled, and experimental study with blind
outcome assessment. METHOD: Fifty Wistar-albino rats were randomized to five
groups; all underwent colocolic anastomosis. P was maintained for 60 min at IAPs
of 14, 20, 25, and 30 mmHg in study groups 1, 2, 3, and 4, respectively; P was
preceded by intraperitoneal L: -NAME (2.5 mg/kg) and followed by anastomosis. The
control group was not subjected to IAP or L: -NAME. RESULTS: Anastomosis bursting
pressure (ABP) values and histopathological findings were determined on the 7th
14th postoperative days. The ABPs of groups 3-4 were significantly lower than the
others. Groups 1-2 had results similar to controls. Histopathological findings of
the groups were consistent with their ABPs. CONCLUSION: Administration of a 2.5
mg/kg intraperitoneal L: -NAME dose was found to provide a beneficial role,
implying a role in impaired anastomotic healing after IAPs of 14 and 20 mmHg.
PMID- 17031696
TI - Cigarette smoking: cancer risks, carcinogens, and mechanisms.
AB - BACKGROUND: Cigarette smoking causes about 30% of all cancer mortality in
developed countries. Although smoking is decreasing in developed countries, it is
increasing in some developing countries. DISCUSSION: Cigarette smoke contains
over 60 well established carcinogens. There are strong links between some of
these carcinogens and various types of smoking-induced cancers. Mechanisms by
which cigarette smoke carcinogens cause cancer are well established and are
discussed here. CONCLUSIONS: A great deal is known about cigarette smoke
carcinogens and the mechanisms by which they cause cancer. It is hoped that this
will provide new insights for the prevention and cure of tobacco-induced cancer.
PMID- 17031697
TI - Anthelmintic action of eprinomectin in lactating Anglo-Nubian goats in Brazil.
AB - Eprinomectin is the only avermectin approved for use to control gastrointestinal
nematodes in lactating cows. Some studies in the USA and Europe have also
demonstrated that this drug is highly effective in small ruminants. The aim of
the present work was to evaluate the anthelmintic efficacy of pour-on
eprinomectin in Anglo-Nubian goats at the end of lactation. Twenty-four goats
were used, naturally infected with gastrointestinal nematodes, and divided into
two groups: control and treated with eprinomectin (Eprinex, Merial, pour-on 0.5%)
at a dose of 850 microg/kg. Counts were made of the eggs per gram (EPG) of feces,
along with coprocultures, on days -7, 0, 4, 8, 11, 15, 18, 22, 25 and 29. The
milk production of each group was recorded throughout the experiment. The
coprocultures detected 98% Haemonchus contortus and 2% Oesophagostomum. There was
no statistically significant difference (P > 0.05) in daily milk output between
the two groups. Eprinomectin at the tested dosage was not effective (P > 0.05) in
reducing the EPG. Positive results would serve as basis for use of an avermectin
without residues in dairy goats, providing a scientific basis for greater food
safety.
PMID- 17031698
TI - Effect of temperature on the development of Schistosoma japonicum within
Oncomelania hupensis, and hibernation of O. hupensis.
AB - The objectives of this investigation were to assess the effect of temperature on
the development of Schistosoma japonicum harboured in Oncomelania hupensis and to
determine the lowest temperature threshold at which the hibernation of O.
hupensis occurs. In the first experiment, adult infection-free O. hupensis,
collected from Jiangsu province in eastern China, were infected with S. japonicum
miracidia and raised at different temperatures under laboratory conditions. The
development of miracidia until the release of cercariae was monitored employing
the cercarial shedding method. In the second experiment, batches of O. hupensis
were kept at temperatures below 13 degrees C with the temperature gradually
reduced. Snail activity was assessed by a pin puncture method. We found a
positive relationship between the development of S. japonicum within O. hupensis
and temperature. In snails kept at 15.3 degrees C, S. japonicum arrested their
development, while the fastest development occurred at 30 degrees C. The
temperature at which half of the snails were in hibernation (ET(50)) was 6.4
degrees C. Our results underscore the pivotal role temperature plays on the
biological activity of O. hupensis and the development of S. japonicum within the
intermediate host. These findings are likely to have implications for the
transmission of schistosomiasis in a warmer future China.
PMID- 17031699
TI - Genotypes and subtypes of Cryptosporidium spp. in neonatal calves in Northern
Ireland.
AB - Cryptosporidium spp. in diarrheic calves less than 30 days old from farms across
Northern Ireland were examined over a year period by microscopic, genotyping, and
subtyping techniques to characterize the transmission dynamics. Cryptosporidium
oocysts were detected in 291 of 779 (37.4%) animals. The prevalence rates of
rotavirus, coronavirus, and Escherichia coli K99+ were lower as seen in 242 of
806 (30.0%), 46/806 (5.7%), and 16/421 (3.8%) of animals, respectively. Of the
224 Cryptosporidium-positive specimens available for molecular analysis,
Cryptosporidium parvum was identified in 213 (95.1%) specimens, Cryptosporidium
bovis in eight (3.6%), and Cryptosporidium deer-like genotype in three (1.3%).
Sequence analysis of the 60-kDa glycoprotein gene identified 16 IIa subtypes and
a new subtype family, with 120 of the 216 (55.6%) positive specimens having the
subtype IIaA18G3R1. Eight of the IIa subtypes were previously seen in humans in
Northern Ireland. Several subtypes were temporally or geographically unique. The
genetic diversity in calves in Northern Ireland was much greater than that
reported from other areas. This work demonstrates the utility of genotyping and
subtyping tools in characterizing the transmission of Cryptosporidium spp. in
calves and humans.
PMID- 17031700
TI - Effects of the herbivorous minnow, southern redbelly dace (Phoxinus
erythrogaster), on stream productivity and ecosystem structure.
AB - We used field and mesocosm experiments to measure effects of southern redbelly
dace (Phoxinus erythrogaster), a grazing minnow, on stream ecosystem structure
and function. Ecosystem structure was quantified as algal filament length, algal
biomass, size distribution of particulate organic matter (POM), algal assemblage
structure, and invertebrate assemblage structure, whereas ecosystem function was
based on gross and net primary productivity. Our experiments showed that moderate
densities of Phoxinus temporarily reduced mean algal filament length and mean
size of POM relative to fishless controls. However, there was no detectable
effect on algal biomass or ecosystem primary productivity. Several factors could
explain the lack of effect of Phoxinus on primary productivity including
increased algal production efficiency in grazed treatments or increased grazing
by other organisms in fishless treatments. The inability of Phoxinus to reduce
algal biomass and system productivity contrasts with experimental results based
on other grazing minnows, such as the central stoneroller (Campostoma anomalum),
and questions the generality of grazer effects in stream ecosystems. However,
environmental venue and the spatial and temporal scale of ecosystem measurements
can greatly influence the outcome of these experiments.
PMID- 17031701
TI - How do soil nutrients affect within-plant patterns of herbivory in seedlings of
Eucalyptus nitens?
AB - This study assessed how the palatability of leaves of different age classes
(young, intermediate and older) of Eucalyptus nitens seedlings varied with plant
nutrient status, based on captive feeding trials with two mammalian herbivores,
red-bellied pademelons (Thylogale billardierii), and common brushtail possums
(Trichosurus vulpecula). Seedlings were grown under three nutrient treatments
(low, medium and high), and we determined how palatability was related to
chemical and physical characteristics of the leaves. Pademelons ate more older
leaves than young and intermediate leaves for all treatments. This pattern was
best explained by sideroxylonals (formylated phloroglucinol compounds known to
deter herbivory by other marsupials), and/or essential oil compounds that were
present in lower concentrations in older leaves. In the low-nutrient treatment,
possums also ate more of the older leaves. However, in the medium- and high
nutrient treatments, possums ate more intermediate leaves than older leaves and
showed a behavioural preference for young leaves (consuming younger leaves first)
over intermediate and older leaves, in spite of high levels of sideroxylonals and
essential oils. The young leaves did, however, have the highest nitrogen
concentration of all the leaf age classes. Thus, either sideroxylonals and
essential oils provided little or no deterrent to possums, or the deterrent was
outweighed by other factors such as high nitrogen. This study indicates that
mammalian herbivores show different levels of relative use and damage to leaf age
classes at varying levels of plant nutrient status and, therefore, their impact
on plant fitness may vary with environment.
PMID- 17031702
TI - Pedicle growth asymmetry as a cause of adolescent idiopathic scoliosis: a
biomechanical study.
AB - Over the last century the neurocentral junction (NCJ) has been identified as a
potential cause of adolescent idiopathic scoliosis (AIS). Disparate growth at
this site has been thought to lead to pedicle asymmetry, which then causes
vertebral rotation and ultimately, the development of scoliotic curves. The
objectives of this study are (1) to incorporate pedicle growth and growth
modulation into an existing finite element model of the thoracic and lumbar spine
already integrating vertebral body growth and growth modulation; (2) to use the
model to investigate whether pedicle asymmetry, either alone or combined with
other deformations, could be involved in scoliosis pathomechanisms. The model was
personalized to the geometry of a nonpathological subject and used as the
reference spinal configuration. Asymmetry of pedicle geometry (i.e. initial
length) and asymmetry of the pedicle growth rate alone or in combination with
other AIS potential pathogenesis (anterior, lateral, or rotational displacement
of apical vertebra) were simulated over a period of 24 months. The Cobb angle and
local scoliotic descriptors (wedging angle, axial rotation) were assessed at each
monthly growth cycle. Simulations with asymmetrical pedicle geometry did not
produce significant scoliosis, vertebral rotation, or wedging. Simulations with
asymmetry of pedicle growth rate did not cause scoliosis independently and did
not amplify the scoliotic deformity caused by other deformations tested in the
previous model. The results of this model do not support the hypothesis that
asymmetrical NCJ growth is a cause of AIS. This concurs with recent animal
experiments in which NCJ growth was unilaterally restricted and no scoliosis,
vertebral wedging, or rotation was noted.
PMID- 17031703
TI - Comment on "A proposal for a surgical classification of pediatric lumbosacral
spondylolisthesis based on current literature" (Jean-Marc Mac-Thiong, Hubert
Labelle).
PMID- 17031704
TI - Tracking the pathway of calcium phosphate/DNA nanoparticles during cell
transfection by incorporation of red-fluorescing tetramethylrhodamine
isothiocyanate-bovine serum albumin into these nanoparticles.
AB - Calcium phosphate nanoparticles were prepared by precipitation from water and
were then functionalized by DNA. These particles are taken up by living cells and
function as gene transfer agents, i.e., the DNA is brought into a cell's nucleus
and is incorporated there into the cell's genome (transfection). DNA which
encodes for enhanced green fluorescent protein leads to green fluorescence of
successfully transfected cells. By adding the red-fluorescing marker
tetramethylrhodamine isothiocyanate-bovine serum albumin (TRITC-BSA) to the
nanoparticles, their pathway into the cell and within the cell could be followed
by fluorescence microscopy. A clear correlation between the uptake of
nanoparticles and the efficiency of transfection was found. Aggregates of
DNA/TRITC-BSA alone were not able to enter the cells, i.e., the inorganic
nanoparticles are necessary as a carrier through the cell membrane.
PMID- 17031705
TI - Pi-pi interaction between aromatic ring and copper-coordinated His81 imidazole
regulates the blue copper active-site structure.
AB - Noncovalent weak interactions play important roles in biological systems. In
particular, such interactions in the second coordination shell of metal ions in
proteins may modulate the structure and reactivity of the metal ion site in
functionally significant ways. Recently, pi-pi interactions between metal ion
coordinated histidine imidazoles and aromatic amino acids have been recognized as
potentially important contributors to the properties of metal ion sites. In this
paper we demonstrate that in pseudoazurin (a blue copper protein) the pi-pi
interaction between a coordinated histidine imidazole ring and the side chains of
aromatic amino acids in the second coordination sphere, significantly influences
the properties of the blue copper site. Electronic absorption and electron
paramagnetic resonance spectra indicate that the blue copper electronic structure
is perturbed, as is the redox potential, by the introduction of a second
coordination shell pi-pi interaction. We suggest that the pi-pi interaction with
the metal ion coordinated histidine imidazole ring modulates the electron
delocalization in the active site, and that such interactions may be functionally
important in refining the reactivity of blue copper sites.
PMID- 17031706
TI - Differences in the cellular mechanism underlying the effects of amphetamine on
prepulse inhibition in apomorphine-susceptible and apomorphine-unsusceptible
rats.
AB - BACKGROUND: Amphetamine is often used to mimic certain aspects of schizophrenia
in laboratory animals, such as a decreased prepulse inhibition. MATERIALS AND
METHODS: Apomorphine-susceptible and apomorphine-unsusceptible rats represent a
well-characterized animal model for individual differences in the sensitivity to
dopaminergic drugs. Moreover, apomorphine-susceptible rats show a wide variety of
schizophrenia-like abnormalities. The differential response to administration of
amphetamine (1-4 mg/kg, i.p.) was investigated in these two rat lines using the
prepulse inhibition paradigm. Because amphetamine promotes dopamine release, the
cellular mechanism underlying the line-specific effects of amphetamine was
investigated by administration of alpha-methyl-para-tyrosine (aMpT) and
reserpine, substances that are known to deplete the cytosolic dopamine pool and
the vesicular dopamine pool, respectively, the former being primarily implicated
in mediating the effects of amphetamine. RESULTS: All doses of amphetamine
decreased prepulse inhibition in apomorphine-susceptible rats, whereas only the
highest doses (2 and 4 mg/kg, i.p.) of amphetamine decreased prepulse inhibition
in apomorphine-unsusceptible rats. Alpha-methyl-para-tyrosine, but not reserpine,
blocked the amphetamine-induced disruption in prepulse inhibition in apomorphine
unsusceptible rats, whereas both substances alone had no effect in apomorphine
susceptible rats. However, the combination of alpha-methyl-para-tyrosine and
reserpine did block the amphetamine-induced effects in the latter rat line.
DISCUSSION: The present study suggests that apomorphine-susceptible rats are more
sensitive to systemic administration of amphetamine than apomorphine
unsusceptible rats. In addition, the data show that the cellular mechanism
underlying the effects of amphetamine differs between apomorphine-susceptible and
apomorphine-unsusceptible rats. Whereas the effects of amphetamine on prepulse
inhibition in apomorphine-unsusceptible rats just require the alpha-methyl-para
tyrosine sensitive dopamine pool, the effects in apomorphine-susceptible rats
require both the alpha-methyl-para-tyrosine sensitive and the reserpine sensitive
dopamine pool. Because apomorphine-susceptible rats share many features with
schizophrenic patients, these data open the perspective that in these patients
amphetamine may induce dopamine release from both types of dopamine pool. This
might provide an explanation for the increased dopamine release after this
psychostimulant drug in patients vs controls.
PMID- 17031707
TI - Cocaine sensitization and dopamine mediation of cue effects in rodents, monkeys,
and humans: areas of agreement, disagreement, and implications for addiction.
AB - BACKGROUND: Sensitization of mesocorticolimbic dopamine projections has been a
valuable model of neurobiological adaptation to chronic exposure to cocaine and
other psychostimulants. DISCUSSIONS: In addition to providing an explanation of
exaggerated responses to drugs that might explain their increased ability to
serve as reinforcers, sensitization has also been incorporated into influential
theories of how drug associated cues can acquire increased salience and incentive
motivation. However, almost all of the work exploring behavioral and
neurochemical sensitization has been conducted in rodents. Importantly, the
relatively small amount of work conducted in human and nonhuman primates differs
from the rodent work in some important regards. This review will examine areas of
convergence and divergence between the rodent and primate literature on
sensitization and the ability of drug associated environmental cues to elicit
dopamine release. The implications of this comparison for expanding addiction
research beyond dopaminergic mechanisms in the striatum/nucleus accumbens will be
considered.
PMID- 17031708
TI - Adderall produces increased striatal dopamine release and a prolonged time course
compared to amphetamine isomers.
AB - RATIONALE: Adderall is currently used for the treatment of Attention-Deficit
Hyperactivity Disorder (ADHD) and is composed of a novel mixture of approximately
24% L-amphetamine and 76% D-amphetamine salts. There are, however, no
investigations of the pharmacological effects of this combination in vivo.
OBJECTIVES: The technique of high-speed chronoamperometry using Nafion-coated
single carbon-fiber microelectrodes was used to study amphetamine-evoked dopamine
(DA) release produced by Adderall, D-amphetamine, or D,L-amphetamine in the
striatum of anesthetized male Fischer 344 (F344) rats. The amphetamine solutions
were locally applied from micropipettes by pressure ejection. RESULTS: Local
applications of Adderall resulted in significantly greater DA release signal
amplitudes with prolonged time course of dopamine release and re-uptake as
compared to D-amphetamine and D,L-amphetamine. CONCLUSIONS: These data support
the hypothesis that the combination of amphetamine enantiomers and salts in
Adderall has effects on DA release, which result in increased and prolonged DA
release, compared to D- and D,L-amphetamine.
PMID- 17031709
TI - Effect of paroxetine on enhanced contextual fear induced by single prolonged
stress in rats.
AB - RATIONALE: Single prolonged stress (SPS) is an animal model of posttraumatic
stress disorder (PTSD) that can reproduce enhanced hypothalamo-pituitary-adrenal
negative feedback. OBJECTIVES: We examined whether SPS can produce an enhanced
psychophysiological reactivity to laboratory stressors unrelated to trauma and
whether paroxetine (PRX) can alleviate the enhanced anxiety and fear response in
rats subjected to SPS. Furthermore, the effect of PRX on pain sensitivity was
examined in rats with and without SPS. METHODS: Rats were subjected to SPS
(restraint for 2 h, forced swim for 20 min, and ether anesthesia) and then kept
undisturbed for 14 days. After that, contextual fear response was assessed.
Twenty-four hours after foot shock conditioning, freezing behavior was measured
during reexposure to the shock environment for 3 min. Pain sensitivity was
assessed by the flinch-jump test. PRX (0.01, 0.03, or 0.1 mg/mL) was chronically
administered orally in drinking water. RESULTS: Rats subjected to SPS showed a
significant increase in contextual freezing compared to rats without SPS. Chronic
administration of PRX at concentrations of 0.03 and 0.1 mg/mL (which produced
serum concentrations similar to those that are clinically relevant) caused
significant suppression of the enhanced contextual freezing. Acute administration
of PRX at a dose producing clinically relevant serum concentrations did not
affect the enhanced freezing. CONCLUSIONS: Our results suggest that SPS can
reproduce behavioral alteration similar to that observed in patients with PTSD,
and this elevated fear response can be alleviated by the chronic administration
of PRX at doses producing clinically relevant serum concentrations.
PMID- 17031711
TI - Tonic dopamine: opportunity costs and the control of response vigor.
AB - RATIONALE: Dopamine neurotransmission has long been known to exert a powerful
influence over the vigor, strength, or rate of responding. However, there exists
no clear understanding of the computational foundation for this effect;
predominant accounts of dopamine's computational function focus on a role for
phasic dopamine in controlling the discrete selection between different actions
and have nothing to say about response vigor or indeed the free-operant tasks in
which it is typically measured. OBJECTIVES: We seek to accommodate free-operant
behavioral tasks within the realm of models of optimal control and thereby
capture how dopaminergic and motivational manipulations affect response vigor.
METHODS: We construct an average reward reinforcement learning model in which
subjects choose both which action to perform and also the latency with which to
perform it. Optimal control balances the costs of acting quickly against the
benefits of getting reward earlier and thereby chooses a best response latency.
RESULTS: In this framework, the long-run average rate of reward plays a key role
as an opportunity cost and mediates motivational influences on rates and vigor of
responding. We review evidence suggesting that the average reward rate is
reported by tonic levels of dopamine putatively in the nucleus accumbens.
CONCLUSIONS: Our extension of reinforcement learning models to free-operant tasks
unites psychologically and computationally inspired ideas about the role of tonic
dopamine in striatum, explaining from a normative point of view why higher levels
of dopamine might be associated with more vigorous responding.
PMID- 17031712
TI - Infantile hypertrophic pyloric stenosis: an infectious cause?
AB - The aetiology of infantile hypertrophic pyloric stenosis (IHPS) remains unclear.
The aim of this study was to test the hypothesis that a common bacterium,
Helicobacter pylori (HP) may be implicated in the pathogenesis of IHPS. Thirty
nine consecutive infants with confirmed IHPS had their stool analysed with an
enzyme immunoassay for the presence of HP. An age/sex-matched group of infants
with unrelated surgical conditions were also tested. No positive results for the
presence of HP stool antigen were obtained in the study nor the control group.
The results of this study demonstrate no causative link between HP and IHPS. A
genetic basis has been implicated for IHPS. However, evidence does exist that
IHPS is a condition acquired after birth and that an infective agent may be
involved in the pathogenesis. Further studies are required to elucidate perinatal
factors that may induce the expression of this condition in a genetically
sensitive individual.
PMID- 17031710
TI - Opioids for hedonic experience and dopamine to get ready for it.
AB - BACKGROUND AND RATIONALE: More than two decades ago, Wise proposed his "anhedonia
hypothesis" to explain the role of dopamine in motivated behaviors. The
hypothesis posits that dopamine mediates the pleasure experienced by reward
obtainment. However, some experimental findings have contested this hypothesis
and several authors have proposed alternative functions for dopamine with regard
to motivation. Brain dopamine has been suggested to rather code for the
preparatory aspects of behavior, while brain opioids seem to mediate the
perception of the hedonic properties of rewards. OBJECTIVES: The main goal of
this review is to reexamine dopamine and opioids involvement in feeding when
different aspects such as the anticipatory, motivational and consummatory
components of this behavior are taken into account, but also when the physiologic
state of the organism and the palatability of the food are considered. RESULTS
AND CONCLUSIONS: Altogether, the data presented point out for an implication of
dopamine in the anticipatory/preparatory aspects of feeding more than on the
motivational and consummatory aspects. However, dopamine involvement in the
anticipatory/preparatory component of feeding seems specifically related to very
relevant stimuli, such as highly palatable foods. On the other hand, our data, as
well as those present in the literature, strongly suggest a role for opioids in
food intake through their modulation of the hedonic perception of food. As a
consequence, opioids are involved in those aspects of motivation driven by food
palatability rather than by food homeostatic need.
PMID- 17031713
TI - Histological evaluation of the testicular nubbins in patients with nonpalpable
testis: assessment of etiology and surgical approach.
AB - There is a controversy in the literature whether testicular nubbins carry
malignancy risk and excision of the nubbin is necessary in patients with
nonpalpable testis. It is also controversial whether vanishing testis has the
same etiopathogenesis and risk with true undescended testis. The aim of this
study is to investigate the histological findings of testicular nubbins in
patients with nonpalpable testis and to question etiology and surgical
indications for vanishing testis. We reviewed the histopathological results of 44
testicular nubbins in 40 patients (mean age: 4.1 years, range 1-13 years) with
nonpalpable testis between 1992 and 2004, retrospectively. Exploration revealed 5
intraabdominal and 39 inguinal testicular nubbins. Of 44 specimens only 5 (11.3%)
from inquinal testicular nubbins were found to have seminiferous tubules. Two of
the five had seminiferous tubule structures with viable germ cells showing
maturation correlating with age. The other two with scarce seminiferous tubules
were seen on only a single area and one had Sertoli cells only. None of the
excised tissue had malignant degeneration. The vas deferens was identified in 23
(52.2%), vessels in 26 (59%), calcification in 14 (31.8%) and hemosiderin in 12
(27.2%) of excised tissue. Presence of calcification in one-third of the nubbins
supports vascular accident thesis in the etiopathogenesis of vanishing testis.
The possibility for the presence of seminiferous tubules and viable germ cells in
the testicular nubbin is low. These facts decrease theoritical risk of
malingnancy. Therefore, an inguinal exploration for testicular nubbin in patients
with vas deferens and vessels entering into the inquinal canal diagnosed at
laparoscopy can be postponed untill testicular prosthesis implantation and the
nubbin can be removed at this operation.
PMID- 17031714
TI - Modulation of respiratory pattern and upper airway muscle activity by the
pedunculopontine tegmentum: role of NMDA receptors.
AB - The pedunculopontine tegmental nucleus (PPT) is postulated to have important
functions relevant to the regulation of rapid eye movement (REM) sleep and
arousal, and various motor control systems including respiration. We have
recently shown that pharmacologic activation of a neuronal subpopulation within
the PPT, induced by micropipette injection of glutamate in nanoliter volumes, can
produce respiratory rhythm disturbances and changes in genioglossus muscle
activity in anesthetized rats. The aim of this study was to determine whether the
respiratory pattern disturbance and increased genioglossus muscle tone induced by
glutamate injection within the PPT are mediated by activation of N-methyl-D
aspartate (NMDA) receptors within the PPT. Experiments were performed in eight
adult male spontaneously breathing Sprague-Dawley rats anesthetized using
nembutal. Respiratory movements were monitored by piezoelectric strain gauge.
Three-barrel glass pipettes were used to pressure inject glutamate (as a probe
for respiratory modulating sites), ketamine (an NMDA channel blocker), and oil
red dye (to aid in histological verification of the injection sites) within the
PPT. Electroencephalograms were recorded from the sensorimotor cortex, the
hippocampus, and the pons, contralateral to the injection site. Electromyograms
(EMGs) were recorded from the genioglossus muscle. The typical response to
glutamate injection within the PPT respiratory-modulating region was immediate
apnea followed by tachypnea and increased genioglossal tonic activity. The
noncompetitive NMDA receptor channel-antagonist ketamine, injected at the same
site and in the same volume as glutamate (5 nl), blocked respiratory dysrhythmia
and genioglossal EMG responses to subsequent glutamate injections. For the first
time, the present results suggest that respiratory rhythm and upper airway muscle
tone are controlled by the activation of pedunculopontine tegmental nucleus NMDA
receptors.
PMID- 17031716
TI - Performance enhancement for audio-visual speaker identification using dynamic
facial muscle model.
AB - Science of human identification using physiological characteristics or biometry
has been of great concern in security systems. However, robust multimodal
identification systems based on audio-visual information has not been thoroughly
investigated yet. Therefore, the aim of this work to propose a model-based
feature extraction method which employs physiological characteristics of facial
muscles producing lip movements. This approach adopts the intrinsic properties of
muscles such as viscosity, elasticity, and mass which are extracted from the
dynamic lip model. These parameters are exclusively dependent on the neuro
muscular properties of speaker; consequently, imitation of valid speakers could
be reduced to a large extent. These parameters are applied to a hidden Markov
model (HMM) audio-visual identification system. In this work, a combination of
audio and video features has been employed by adopting a multistream pseudo
synchronized HMM training method. Noise robust audio features such as Mel
frequency cepstral coefficients (MFCC), spectral subtraction (SS), and relative
spectra perceptual linear prediction (J-RASTA-PLP) have been used to evaluate the
performance of the multimodal system once efficient audio feature extraction
methods have been utilized. The superior performance of the proposed system is
demonstrated on a large multispeaker database of continuously spoken digits,
along with a sentence that is phonetically rich. To evaluate the robustness of
algorithms, some experiments were performed on genetically identical twins.
Furthermore, changes in speaker voice were simulated with drug inhalation tests.
In 3 dB signal to noise ratio (SNR), the dynamic muscle model improved the
identification rate of the audio-visual system from 91 to 98%. Results on
identical twins revealed that there was an apparent improvement on the
performance for the dynamic muscle model-based system, in which the
identification rate of the audio-visual system was enhanced from 87 to 96%.
PMID- 17031715
TI - Finite difference and lead field methods in designing implantable ECG monitor.
AB - To minimize time-consuming and expensive in vitro and in vivo testing,
information regarding the effects of implantation and the implants on
measurements should be available during the designing of active implantable
devices measuring bioelectric signals such as electrocardiograms (ECG). Modeling
offers a fairly inexpensive and effective means of studying and demonstrating the
effects of implantation on ECG measurements prior to any in vivo tests, and can
thus provide the designer with valuable information. Finite difference model
(FDM) and lead field approaches offer straightforward and effective modeling
methods supporting the designing of active implantable ECG devices. The present
study demonstrates such methods in developing and studying ECG implants. They
were applied in demonstrating the effects of implant dimensions and of electrode
implantation on the measurement sensitivity of the ECG device. The results of the
simulations indicated that the interelectrode distance is the factor of the
implant design determining the lead sensitivity. Other parameters related implant
dimensions and shape have minor effect on the morphology of the ECG or on the
average sensitivity of the measurement. This is shown for example when the
interelectrode distance was reduced to 1/3 of original the average lead
sensitivity decreased by 69.1% while larger relative changes in other dimensions
produced clearly smaller changes. It was also observed here that implanting the
electrodes deeper under the skin has major effects on the local sensitivities in
heart muscle and thus affect to the morphology of the ECG. The study indicated
also that non-conducting medium (i.e. implant insulated body) between the
electrodes increases the sensitivity on heart muscle compared to cases where only
electrodes are implanted.
PMID- 17031717
TI - Histopathological workup of an Amplatzer atrial septal defect occluder after
surgical removal.
AB - We present results of the histopathological work-up of an atrial septal defect
occluder that was explanted 15 months after interventional implantation due to a
significant residual shunt. Complete endothelialization of the surface and a mild
inflammatory reaction was demonstrated.
PMID- 17031718
TI - Autologous Ross operation for congenital aortic stenosis.
AB - Congenital aortic stenosis is a relatively common cardiac anomaly encountered in
approximately 5% of all children with heart disease. The Ross procedure is
increasingly used for replacement of the aortic valve in children. We report a 12
year-old boy who was born with congenital aortic stenosis secondary to a
bicommissural aortic valve. The patient underwent open valvotomy in infancy and
aortic valvuloplasty 2 years later. Residual/recurrent stenosis prompted referral
for aortic valve replacement, and he underwent an autologous Ross procedure, in
which the aortic root was replaced with a pulmonary autograft and the repaired
aortic valve was used to restore right ventricular-to-pulmonary artery
continuity. The postoperative course was unremarkable. Nitroprusside, esmolol,
and labetolol were used to control postoperative hypertension. He was discharged
4 days after surgery on oral furosemide and aspirin, and he has had no
cardiovascular symptoms during follow-up. Recent echocardiography demonstrated
mild right ventricular outflow tract obstruction with a peak velocity of 3.6
m/sec, with a gradient of 42 mmHg and moderate pulmonary insufficiency. There was
no left ventricular outlet tract obstruction or aortic insufficiency.
PMID- 17031719
TI - Double-orifice mitral valve associated with noncompaction of left ventricular
myocardium.
AB - Double-orifice mitral valve (DOMV) is a rare anomaly commonly associated with
other congenital heart diseases. We present two patients with DOMV and
noncompaction of the left ventricular myocardium (NLVM). Case 1 was a 5-year-old
male diagnosed with dilated cardiomyopathy. His echocardiogram showed thin
myocardium with dilatation at the basal of the left ventricle, thick noncompacted
myocardium around the apex of the left ventricle, and DOMV (complete bridge type)
with mild mitral regurgitation. Case 2 was an 11-year-old male diagnosed with
complete atrioventricular block. His echocardiogram showed thick noncompacted
myocardium with mild hypokinesis from the posterior to lateral wall and DOMV
(complete bridge type) with mild mitral regurgitation. DOMV is commonly
associated with congenital anomaly and always has an abnormal subvalvar
apparatus. The mitral valve and its apparatus embryologically originate from the
endomyocardium, which is thought to be the origin of noncompacted myocardium. We
speculate that patients with DOMV may have NLVM.
PMID- 17031720
TI - 1173C>T polymorphism in VKORC1 modulates the required warfarin dose.
AB - The response to warfarin is highly variable among individuals and such
variability is likely to have some genetic basis. We evaluted the effect of
VKORC1 polymorphisms on warfarin response among Japanese, taking advantage of its
unique population structure in which CYP2C9 *2 and *3 alleles are relatively
rare. Thirty-one patients (12-34 years old; median, 22) on warfarin were
recruited from a pediatric cardiology clinic. Genotyping of the C>T polymorphism
at position 1173 in intron 1 of VKORC1 revealed that 26 patients (84%) were T/T
homozygotes at nucleotide 1173, whereas 5 (16%) were C/T heterozygotes. Complete
linkage disequilibrium was observed between the 1173C > T polymorphism and
another polymorphism, the 3730G > A, in the 3' untranslated region. The C/T
heterozyogtes at the 1173C > T polymorphism tended to require more warfarin than
the T/T homozygotes, when adjusted for international normalized ratio (p =
0.003). Both the 1173C > T polymorphism and the 3730G > A polymorphism are likely
to be inert from a functional standpoint. Rather, based on the complete linkage
disequilibrium between 1173C > T and 3730G > A polymorphisms, we suspect that the
actual change that defines the relative resistance to warfarin may be present in
the proximity of these two polymorphisms.
PMID- 17031721
TI - Noninvasive visualization and measurement of middle cardiac vein flow by
transthoracic Doppler echocardiography.
AB - Transthoracic Doppler echocardiography offers a noninvasive approach for imaging
posterior descending coronary artery (PD) running in the posterior longitudinal
sulcus along the middle cardiac vein (MCV). To evaluate whether the MCV flow
velocity reserve can reflect the PD flow reserve, 22 children with various heart
diseases were examined using transthoracic Doppler echocardiography. Introduction
of a modified transthoracic two chamber view with the transducer rotated
counterclockwise and angulated posteriorly allows visualization of the MCV and
PD. Peak systolic flow velocity and average peak systolic flow velocity in the
MCV and peak diastolic flow velocity and average peak diastolic flow velocity in
the PD were measured at rest and hyperemic conditions (intravenous administration
of adenosine of 0.16 mg/kg/min). Coronary flow reserve was defined as the ratio
of peak hyperemic to basal average peak flow velocity. ATP infusion induced
significant increases in the peak systolic flow velocity and average peak
systolic flow velocity in the MCV. The mean MCV flow velocity reserve in the
patients was 1.94 +/- 0.44. Significant increases in the peak diastolic flow
velocity and the average peak diastolic flow velocity in the PD were also
observed during ATP infusion, and the mean PD flow velocity reserve (2.19 +/-
0.62) was significantly higher than the GCV flow velocity reserve (p < 0.0001).
There was a good correlation between the MCV flow velocity reserve and PD flow
velocity reserve (r = 0.86, p < 0.0001). This study demonstrated that it was
possible to measure the MCV flow velocity and MCV flow velocity reserve in
pediatric patients by transthoracic Doppler echocardiography. The MCV flow
reserve correlated highly with the PD flow reserve. However, the degree of the
MCV flow during hyperemia was less than that of the PD flow. This underestimation
should be considered when the reactive hyperemic response is evaluated from the
MCV flow velocity.
PMID- 17031722
TI - Morbidity and mortality assessment of cytoreductive surgery and perioperative
intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma--a
prospective study of 70 consecutive cases.
AB - BACKGROUND: Although many reports regarding morbidity and mortality of
cytoreductive surgery plus perioperative intraperitoneal chemotherapy are
available, there are no prospective data on morbidity and mortality limited to
patients with diffuse malignant peritoneal mesothelioma (DMPM). METHODS: This
prospective morbidity and mortality assessment was performed on 70 consecutive
cytoreductive procedures with perioperative intraperitoneal chemotherapy for
DMPM. Forty-seven adverse events by eight categories were rated from grades I to
IV with increasing severity. Grade I morbidity was self-limiting; grade II
required medical treatments; grade III required an invasive intervention; grade
IV required returning to the operating room or intensive care management. Risk
factors for grades III and IV morbidity were determined. RESULTS: The
perioperative mortality rate was 3%. The grades III and IV morbidity rates were
27 and 14%, respectively. Primary colonic anastomosis (P = 0.028), more than four
peritonectomy procedures (P = 0.015), duration of the operation of more than 7 h
(P = 0.027) were the risk factors for grade IV morbidity. Survival analysis of
these 70 patients was provided. CONCLUSIONS: The morbidity and mortality results
for cytoreductive surgery and perioperative intraperitoneal chemotherapy for
patients with DMPM were within the acceptable range for major gastrointestinal
surgery. Grade IV morbidity was associated with more extensive cytoreduction.
PMID- 17031723
TI - Stent-graft repair of peroneal arteriovenous fistula.
AB - Arteriovenous fistulas (AVFs) are infrequently seen in the civilian health-care
system; traditionally, these lesions have been treated with ligation, or direct
surgical repair with concomitant revascularization. We describe a rare case of a
peroneal AVF treated with a stent-graft.
PMID- 17031724
TI - Missed total occlusion due to the occipital artery arising from the internal
carotid artery.
AB - A 56-year-old man was referred for digital subtraction angiography (DSA) with an
ultrasound diagnosis of right proximal internal carotid artery (ICA) stenosis for
possible carotid artery stenting. DSA revealed total occlusion of the ICA and an
occipital artery arising from the stump and simulating continuation of the ICA.
An ascending pharyngeal artery also arose from the same occipital artery. This
case is of interest because this is a rare variation besides being a cause of
misdiagnosis at carotid ultrasound.
PMID- 17031725
TI - Spontaneous rupture of the hepatic artery in a patient with type 1
neurofibromatosis treated by embolization: a case report.
AB - We report the case of a 48-year-old man with neurofibromatosis presenting with
sudden-onset abdominal pain, profound hypotension, and a drop in hemoglobin. CT
scan demonstrated a massive hematoma within the right lobe of the liver with
rupture into the peritoneal cavity. Angiography demonstrated diffuse
abnormalities of the hepatic circulation with fusifom, ectatic, and stenotic
segments. Acute extravasation from a peripheral branch of the right hepatic
artery was identified and successfully embolized with subsequent hemodynamic
stabilization of the patient. To the best of our knowledge this is the first case
report of this kind in a patient with type I neurofibromatosis.
PMID- 17031726
TI - Iatrogenic aorto-cisterna chyli fistula during percutaneous balloon aortoplasty
in a patient with Takayasu's arteritis: a case report.
AB - We present a case of iatrogenic aorto-cisterna chyli fistula that developed
during percutaneous transluminal aortoplasty in a 16-year old girl with
Takayasu's arteritis. The aorto-cisterna chyli fistula was angiographically
confirmed and treated using a stent-graft, which successfully occluded the
fistula. Her claudication then improved, although follow-up CT angiography at 10
months revealed mild recurrent aortic stenosis.
PMID- 17031727
TI - Right gastric artery embolization prior to treatment with yttrium-90
microspheres.
AB - PURPOSE: Intra-arterial infusion of yttrium-90 microspheres is a form of
radiation treatment for unresectable hepatic neoplasms. Misdeposition of
particles in the gastroduodenal area such as the right gastric artery (RGA) may
occur with serious consequences. We present a series of patients who underwent a
detailed vascular study followed by RGA embolization. Special emphasis is placed
on anatomic variations and technical considerations. METHODS: In a 1 year period,
27 patients were treated. Initial vascular evaluation was performed, with careful
attention to anatomic variants or extrahepatic arterial supply, especially to the
gastroduodenal area. Embolization of such arteries was planned if needed. RGA
embolization was performed antegradely from the hepatic artery or retrogradely
via the left gastric artery (LGA). Postprocedural follow-up included clinical
interview and gastroscopy if necessary. RESULTS: RGA embolization was performed
in 9 patients presenting with primary (n = 3) or metastatic liver tumors (n = 6).
Six patients underwent antegrade RGA embolization and 3 had embolization done
retrogradely via the LGA. Retrograde access was chosen for anatomic reasons. None
of the patients complained of gastroduodenal symptoms. CONCLUSION: RGA
embolization can help minimize the gastroduodenal deposition of radioactive
particles. RGA embolization should routinely be carried out. The procedure can be
performed, with similar technical success, by both anterograde and retrograde
approaches.
PMID- 17031728
TI - Palliative airway stenting performed under radiological guidance and local
anesthesia.
AB - PURPOSE: To assess the effectiveness of airway stenting performed exclusively
under radiological guidance for the palliation of malignant tracheobronchial
strictures. METHODS: We report our experience in 16 patients with malignant
tracheobronchial stricture treated by insertion of 20 Ultraflex self-expandable
metal stents performed under fluoroscopic guidance only. Three patients presented
dysphagia grade IV due to esophageal malignant infiltration; they therefore
underwent combined airway and esophageal stenting. All the procedures were
performed under conscious sedation in the radiological room; average procedure
time was around 10 min, but the airway impediment never lasted more than 40 sec.
RESULTS: We obtained an overall technical success in 16 cases (100%) and clinical
success in 14 patients (88%). All prostheses were successfully placed without
procedural complications. Rapid clinical improvement with symptom relief and
normalization of respiratory function was obtained in 14 cases. Two patients died
within 48 hr from causes unrelated to stent placement. Two cases (13%) of
migration were observed; they were successfully treated with another stent. Tumor
overgrowth developed in other 2 patients (13%); however, no further treatment was
possible because of extensive laryngeal infiltration. CONCLUSIONS:
Tracheobronchial recanalization with self-expandable metal stents is a safe and
effective palliative treatment for malignant strictures. Airway stenting
performed exclusively under fluoroscopic view was rapid and well tolerated.
PMID- 17031729
TI - Aorta-left renal vein fistula complicating an aortic aneurysm: preoperative and
postoperative multislice CT findings.
AB - Fistulas complicating an abdominal aortic aneurysm (AAA) are rare, and fistulas
involving the left renal vein are particularly uncommon. We highlight here a
fistula between an infrarenal aortic aneurysm and a retroaortic left renal vein,
revealed by left flank pain associated with hematuria and acute renal failure.
The multislice CT angiography performed in this 68-year-old patient revealed
communication and equal enhancement between the aorta and the left gonadic vein,
suggesting the presence of a fistula. The three-dimensional VRT reconstructions
presented in this case were of great value in the preoperative planning, enabling
immediate visualization of this unusual feature. Alternative diagnoses to
consider when encountering this clinical presentation are reviewed.
PMID- 17031730
TI - Interventional treatment of a symptomatic neonatal hepatic cavernous hemangioma
using the Amplatzer vascular plug.
AB - Percutaneous intervention is one treatment option for symptomatic hepatic
hemangioma in infants. We report the case of a newborn (birth weight 4060 g) with
a large hepatic cavernous hemangioma, which presented early with high cardiac
output failure due to arteriovenous shunting and signs of incipient Kasabach
Merritt syndrome. We performed a successful superselective transcatheter coil
embolization of three feeding arteries on the seventh day of life. Because of
remaining diffuse very small arteries causing a relevant residual shunt,
additional occlusion of the three main draining veins was necessary with three
Amplatzer vascular plugs. Cardiac failure resolved immediately. Without any
additional therapy the large venous cavities disappeared within the following
months. The tumor continues to regress in size 8 months after the intervention.
PMID- 17031731
TI - Leiomyosarcoma of the uterus with intravascular tumor extension and pulmonary
tumor embolism.
AB - We report the case of a 48-year-old woman presenting with recurrent uterine
leiomyosarcoma (LMS) associated with right iliac vein and inferior vena cava
(IVC) invasion and left lower lobe pulmonary tumor embolus. Because the prognosis
and treatment differ from that of thrombotic pulmonary emboli, the
differentiating imaging characteristics of intravascular tumor embolism are
reviewed. To our knowledge, only two other cases of intravenous uterine
leiomyosarcomatosis have been described in the existing literature, and this is
the first reported case of the entity with associated intravascular tumor
embolism.
PMID- 17031732
TI - Superior mesenteric artery pseudoaneurysm following pancreaticoduodenectomy:
management by endovascular stent-graft placement and transluminal thrombin
injection.
AB - Superior mesenteric artery (SMA) pseudoaneurysm formation is a rare and
potentially fatal postoperative complication. Herein we present a case of a large
post-pancreaticoduodenectomy SMA pseudoaneurysm that required thrombin injection
after initial stent-graft deployment to accomplish complete pseudoaneurysm
occlusion.
PMID- 17031733
TI - A survival analysis of patients with malignant biliary strictures treated by
percutaneous metallic stenting.
AB - BACKGROUND: Percutaneous metal stenting is an accepted palliative treatment for
malignant biliary obstruction. Nevertheless, factors predicting survival are not
known. METHODS: Seventy-six patients with inoperable malignant biliary
obstruction were treated with percutaneous placement of metallic stents. Twenty
patients had non-hilar lesions. Fifty-six patients had hilar lesions classified
as Bismuth type I (n = 15 patients), type II (n = 26), type III (n = 12), or type
IV (n = 3 patients). Technical and clinical success rates, complications, and
long-term outcome were recorded. Clinical success rates, patency, and survival
rates were compared in patients treated with complete (n = 41) versus partial (n
= 35) liver parenchyma drainage. Survival was calculated and analyzed for
potential predictors such as the tumor type, the extent of the disease, the level
of obstruction, and the post-intervention bilirubin levels. RESULTS: Stenting was
technically successful in all patients (unilateral drainage in 70 patients,
bilateral drainage in 6 patients) with an overall significant reduction of the
post-intervention bilirubin levels (p < 0.001), resulting in a clinical success
rate of 97.3%. Clinical success rates were similar in patients treated with whole
liver drainage versus partial liver drainage. Minor and major complications
occurred in 8% and 15% of patients, respectively. Mean overall primary stent
patency was 120 days, while the restenosis rate was 12%. Mean overall secondary
stent patency was 242.2 days. Patency rates were similar in patients with
complete versus partial liver drainage. Mean overall survival was 142.3 days.
Survival was similar in the complete and partial drainage groups. The post
intervention serum bilirubin level was an independent predictor of survival (p <
0.001). A cut-off point in post-stenting bilirubin levels of 4 mg/dl dichotomized
patients with good versus poor prognosis. Patient age and Bismuth IV lesions were
also independent predictors of survival. CONCLUSIONS: Percutaneous metallic
biliary stenting provides good palliation of malignant jaundice. Partial liver
drainage achieved results as good as those after complete liver drainage. A serum
bilirubin level of less than 4 mg/dl after stenting is the most important
independent predictor of survival, while increasing age and Bismuth IV lesions
represent dismal prognostic factors.
PMID- 17031734
TI - Cost and reimbursement for three fibroid treatments: abdominal hysterectomy,
abdominal myomectomy, and uterine fibroid embolization.
AB - PURPOSE: To compare costs and reimbursements for three different treatments for
uterine fibroids. METHODS: Costs and reimbursements were collected and analyzed
from the Thomas Jefferson University Hospital decision support database from 540
women who underwent abdominal hysterectomy (n = 299), abdominal myomectomy (n =
105), or uterine fibroid embolization (UFE) (n = 136) for uterine fibroids during
2000-2002. We used the chi-square test and ANOVA, followed by Fisher's Least
Significant Difference test, for statistical analysis. RESULTS: The mean total
hospital cost (US dollar) for UFE was 2,707 dollars, which was significantly less
than for hysterectomy (5,707 dollars) or myomectomy (5,676 dollars) (p < 0.05).
The mean hospital net income (hospital net reimbursement minus total hospital
cost) for UFE was 57 dollars, which was significantly greater than for
hysterectomy (-572 dollars) or myomectomy (-715 dollars) (p < 0.05). The mean
professional (physician) reimbursements for UFE, hysterectomy, and myomectomy
were 1,306 dollars, 979 dollars, and 1,078 dollars, respectively. CONCLUSION: UFE
has lower hospital costs and greater hospital net income than abdominal
hysterectomy or abdominal myomectomy for treating uterine fibroids. UFE may be
more financially advantageous than hysterectomy or myomectomy for the insurer,
hospital, and health care system. Costs and reimbursements may vary amongst
different hospitals and regions.
PMID- 17031735
TI - Percutaneous retrieval of misplaced intravascular foreign objects with the Dormia
basket: an effective solution.
AB - PURPOSE: We report our experience of the retrieval of intravascular foreign body
objects by the percutaneous use of the Gemini Dormia basket. METHODS: Over a
period of 2 years we attempted the percutaneous removal of intravascular foreign
bodies in 26 patients. Twenty-six foreign bodies were removed: 8 intravascular
stents, 4 embolization coils, 9 guidewires, 1 pacemaker lead, and 4 catheter
fragments. The percutaneous retrieval was achieved with a combination of guide
catheters and the Gemini Dormia basket. RESULTS: Percutaneous retrieval was
successful in 25 of 26 patients (96.2%). It was possible to remove all the
intravascular foreign bodies with a combination of guide catheters and the Dormia
basket. No complication occurred during the procedure, and no long-term
complications were registered during the follow-up period, which ranged from 6
months to 32 months (mean 22.4 months overall). CONCLUSION: Percutaneous
retrieval is an effective and safe technique that should be the first choice for
removal of an intravascular foreign body.
PMID- 17031736
TI - CT-based evaluation of tumor volume after intra-arterial chemotherapy of locally
advanced carcinoma of the oral cavity: comparison with clinical remission rates.
AB - PURPOSE: To assess the volume of locally advanced tumors of the oral cavity and
the oropharynx before and after intra-arterial (i.a.) chemotherapy by means of
computed tomography and to compare these data with clinically determined
treatment response of the same patient population. METHODS: Eighty-eight patients
with histologically proven, advanced carcinoma of the oral cavity and/or the
oropharynx (local tumor stages T3/4) received neoadjuvant i.a. chemotherapy with
cisplatin as part of a multimodal therapeutic regimen, comprising (1) local
chemotherapy, (2) surgery, and (3) combined radio-chemotherapy. Three weeks after
the intervention, residual disease was evaluated radiologically by measurement of
the tumor volume and clinically by inspection and palpation of the primary tumor
according to WHO criteria. RESULTS: Comparison of treatment response according to
radiological and clinical criteria respectively revealed complete remission in 5%
vs. 8% (p < 0.05), partial remission in 30% vs. 31%, stable disease in 61% vs.
58%, and tumor progression in 5% vs. 2%. CONCLUSION: Radiological volumetry and
clinical evaluation found comparable response rates after local chemotherapy.
However, in patients with good response after local treatment, volumetric
measurement with CT may help to distinguish between partial and complete
remission. Thus, radiological tumor volumetry provides precise and differentiated
information about tumor response and should be used as an additional tool in
treatment monitoring after local chemotherapy.
PMID- 17031737
TI - Histologic results 1 year after bioprosthetic repair of paraesophageal hernia in
a canine model.
AB - BACKGROUND: The use of prosthetic materials for the repair of paraesophageal
hiatal hernia (PEH) may lead to esophageal stricture and perforation. High
recurrence rates after primary repair have led surgeons to explore other options,
including various bioprostheses. However, the long-term effects of these newer
materials when placed at the esophageal hiatus are unknown. This study assessed
the anatomic and histologic characteristics 1 year after PEH repair using a U
shaped configuration of commercially available small intestinal submucosa (SIS)
mesh in a canine model. METHODS: Six dogs underwent laparoscopic PEH repair with
SIS mesh 4 weeks after thoracoscopic creation of PEH. When the six dogs were
sacrificed 12 months later, endoscopy and barium x-ray were performed, and
biopsies of the esophagus and crura were obtained. RESULTS: The mean weight of
the dogs 1 year after surgery was identical to their entry weight. No dog had
gross dysphagia, evidence of esophageal stricture, or reherniation. At sacrifice,
the biomaterial was not identifiable grossly. Biopsies of the hiatal region
showed fibrosis as well as muscle fiber proliferation and regeneration. No dog
had erosion of the mesh into the esophagus. CONCLUSIONS: This reproducible canine
model of PEH formation and repair did not result in erosion of SIS mesh into the
esophagus or in stricture formation. Native muscle ingrowth was noted 1 year
after placement of the biomaterial. According to the findings, SIS may provide a
scaffold for ingrowth of crural muscle and a durable repair of PEH over the long
term.
PMID- 17031738
TI - Laparoscopic partial splenectomy.
AB - BACKGROUND: The immunologic function of the spleen and its important role in
immune defense has led to splenic-preserving surgery. This study aimed to
evaluate whether laparoscopic partial splenectomy is safe. METHODS: Data on
consecutive patients presenting with localized benign or malignant disease of the
spleen were included in a prospective database. The surgical technique consisted
of six steps: patient positioning and trocar placement, mobilization of the
spleen, vascular dissection, parenchymal resection, sealing/tamponading of the
transected edge, and removal of the specimen. RESULTS: From 1994 to 2005, 38
patients underwent laparoscopic partial splenectomy. The indications included
splenomegaly of unknown origin, splenic cysts, benign tumors (hamartoma), and
metastasis from ovarian carcinoma and schwannoma. The median operating time was
110 min (range, 65-148 min). The median length of hospital stay was 5 days
(range, 4-7 days). There was no postoperative mortality. Postoperative pleural
effusion occurred in two patients. There were no reoperations. Three patients
required blood transfusions. CONCLUSION: Laparoscopic partial splenectomy is safe
for patients with localized benign or malignant disease of the spleen.
PMID- 17031739
TI - Quantification of process measures in laparoscopic suturing.
AB - BACKGROUND: Process measures describing the generation of movement are useful for
evaluation and performance feedback purposes. This study aimed to identify
process measures that differ between novice and advanced laparoscopists while
completing a suturing skill. METHODS: A group of junior and a group of senior
residents and fellows in surgery (n = 6) placed 10 laparoscopic sutures in a
synthetic model. Process measures were quantified using an opto-electric
motion/force sensor assembly that recorded: instrument rotation, applied forces,
time, and time delays between force application and instrument rotation. RESULTS:
Advanced trainees showed increased instrument rotation, higher peak applied
force, and faster performance compared to novices (alll p < .01). However, over
trials, only novices showed adaptations for instrument rotation and total time
(interactions at p < .01) with no adaptation for the force application. The
difference between the moments of force application and instrument rotation was
not sensitive to participant training. CONCLUSIONS: Movement process measures can
enhance our understanding of early adaptation processes and how such factors
might be used as feedback to facilitate skill acquisition.
PMID- 17031740
TI - Conversion rate for laparoscopic cholecystectomy after endoscopic retrograde
cholangiography in the treatment of choledocholithiasis: does the time interval
matter?
PMID- 17031741
TI - Laparoscopic ventral recto(colpo)pexy for rectal prolapse: surgical technique and
outcome for 109 patients.
AB - The authors propose a new laparoscopic technique for correction of rectal
prolapse. The unique feature of this technique is that it avoids any
posterolateral dissection of the rectum. The mesh is sutured to the anterior
aspect of the rectum to inhibit intussusception. The technique was applied in 109
consecutive patients to correct total rectal prolapse. Conversion was needed for
four patients. No postoperative mortality or major morbidity occurred. Minor
morbidity was noted for 7% of the patients, and a recurrence rate of 3.66% was
observed. Because this technique limited the dissection and the subsequent risk
of autonomic nerve damage, a cure comparable with that resulting from classical
mesh rectopexy can be anticipated.
PMID- 17031742
TI - Laparoscopic esophagogastrectomy without thoracic or cervical access for
adenocarcinoma of the gastroesophageal junction: an Indian experience from a
tertiary center.
AB - BACKGROUND: The phenomenal progress of minimally invasive surgery has imparted
its influence on conventional esophagectomy. Currently, more esophagectomies are
being performed by laparoscopic and/or thoracoscopic methods. Esophagogastrectomy
for the adenocarcinoma of the gastroesophageal (GE) junction has been a
conventional treatment. The literature is limited regarding the laparoscopic
approach to esophagogastrectomy. The aim of this study was to evaluate the
outcome of laparoscopic esophagogastrectomy in the management of adenocarcinoma
of the GE junction. METHODS: From January 1997 to February 2005, laparoscopic
esophagogastrectomy was performed in 32 patients. Indication for operation was
adenocarcinoma of the GE junction in all patients. Neo-adjuvant therapy was used
in two patients (6.88%) only. Initially, our approach to intrathoracic
anastomosis without thoracic and cervical access was to introduce the anvil of
circular stapler through minilaparotomy incision (n = 22), but later we switched
to trans-oral placement of anvil into the distal end of the esophagus (n = 10).
RESULTS: There were 22 men and 10 women. Median age was 61.8 years (range, 39
72). There was no conversion. The laparoscopic esophagogastrectomy was completed
in all patients. The pyloromyotomy and feeding jejunostomy were performed in all
cases. The median intensive care unit stay was 1 day (range, 1-28); hospital stay
was 7 days (range, 5-42). Mean estimated blood loss and mean operative time were
150 ml and 200 min, respectively. At mean follow-up of 14 months (range, 2-40),
stage-specific survival was similar to that of other series. CONCLUSION: In
selected cases of adenocarcinoma of the GE junction, laparoscopic
esophagogastrectomy offers as good as or better results than open operation in
our institution with extensive advance endoscopic and open experience. This study
shows that laparoscopic esophagogastrectomy has potential to meet oncologic
criteria of clearance and provide the benefits of minimally invasive surgery as
well.
PMID- 17031743
TI - Total and subtotal laparoscopic gastrectomy for adenocarcinoma.
AB - BACKGROUND: Laparoscopic gastrectomies are currently performed in many centers,
but compliance with oncologic requirements still represents a subject open to
debate. The aim of this work was to compare the short-term and oncologic outcomes
after laparoscopic and open surgery in gastric adenocarcinoma. METHODS: From June
2000 through June 2005, 147 patients in our institution underwent gastrectomy by
open or mininvasive approach for adenocarcinoma. The laparoscopy group included
48 patients, 29 with early gastric cancer (EGC) and 19 with antral advanced
gastric cancer (AGC). The short-term results and oncologic data were compared to
those obtained in 99 patients who underwent open surgery. Survival in the
laparoscopy group was analyzed. RESULTS: In the laparoscopy group no
intraoperative complications were observed, and conversion was needed in only one
patient with a large advanced tumor. Overall, 32 lymph nodes were collected by D2
dissection, 30 for EGC, 34 for advanced cancers. The resection margin was 6.7 cm
(range: 4-8 cm). The mean operating time was 240 min (range: 150-360 min), with a
blood loss of 150 ml on average (range: 70-250 ml). Morbidity included two
duodenal leaks that healed without reoperation; after enclosing or reinforcing
the staple line, no further leaking was noted. There was one death from massive
bleeding in a cirrhotic patient. Ambulation and oral feeding started
significantly earlier than in open surgery. The mean hospital stay was 10 days
(range: 7-24 days), significantly shorter than the stay of 18 days after open
surgery (p < 0.05). All patients treated laparoscopically were alive without
recurrence at the end of this study. CONCLUSIONS: Short-term results with
laparoscopic gastrectomy were better than with open surgery in this study.
Oncologic radicality was a major concern, but in the authors' experience the
extent of lymphadenectomy was the same as in open surgery. This study suggests
that laparoscopic gastrectomy in malignancies is a reliable tool and oncologic
requirements can be warranted.
PMID- 17031744
TI - Medium- and long-term outcome of laparoscopic redo fundoplication.
AB - BACKGROUND: For a small subset of patients, laparoscopic fundoplication fails,
typically resulting in recurrent reflux or severe dysphagia. Although redo
fundoplications can be performed laparoscopically, few studies have examined
their long-term efficacy. METHODS: Using a prospectively maintained database, the
authors identified and contacted 41 patients who had undergone redo laparoscopic
fundoplications at the University of Washington between 1996 and 2001. The median
follow-up period was 50 months (range, 20-95 months). Current symptoms were
compared with those acquired and entered into the authors' database
preoperatively. Patients also were asked to return for esophageal manometry and
pH testing. RESULTS: All redo fundoplications were performed laparoscopically.
There were no conversions. The most common indication for redo fundoplication was
recurrent reflux. The most common anatomic abnormality was a herniated wrap.
Heartburn improved in 61%, regurgitation in 69%, and dysphagia in 74% of the
patients. Complete resolution of these symptoms was achieved, respectively, in
45%, 41% and 38% of these same patients. Overall, 68% of the patients rated the
success of the procedure as either "excellent" or "good," and 78% said they were
happy they chose to have it. For those who underwent reoperation for
gastroesophageal reflux disease, distal esophageal acid exposure according to 24
h pH monitoring decreased after redo fundoplication from 15.7% +/- 18.1% to 3.4%
+/- 3.6% (p = 0.041). CONCLUSION: Although not as successful as primary
fundoplication, a majority of patients can expect durable improvement in their
symptoms with a laparoscopic redo fundoplication.
PMID- 17031745
TI - Deployment and early experience with remote-presence patient care in a community
hospital.
AB - BACKGROUND: The introduction of the RP6 (InTouch Health, Santa Barbara, CA, USA)
remote-presence "robot" appears to offer a useful telemedicine device. The
authors describe the deployment and early experience with the RP6 in a community
hospital and provided a live demonstration of the system on April 16, 2005 during
the Emerging Technologies Session of the 2005 SAGES Meeting in Fort Lauderdale,
Florida. METHODS: The RP6 is a 5-ft 4-in. tall, 215-pound robot that can be
remotely controlled from an appropriately configured computer located anywhere on
the Internet (i.e., on this planet). The system is composed of a control station
(a computer at the central station), a mechanical robot, a wireless network (at
the remote facility: the hospital), and a high-speed Internet connection at both
the remote (hospital) and central locations. The robot itself houses a
rechargeable power supply. Its hardware and software allows communication over
the Internet with the central station, interpretation of commands from the
central station, and conversion of the commands into mechanical and nonmechanical
actions at the remote location, which are communicated back to the central
station over the Internet. The RP6 system allows the central party (e.g.,
physician) to control the movements of the robot itself, see and hear at the
remote location (hospital), and be seen and heard at the remote location
(hospital) while not physically there. RESULTS: Deployment of the RP6 system at
the hospital was accomplished in less than a day. The wireless network at the
institution was already in place. The control station setup time ranged from 1 to
4 h and was dependent primarily on the quality of the Internet connection
(bandwidth) at the remote locations. Patients who visited with the RP6 on their
discharge day could be discharged more than 4 h earlier than with conventional
visits, thereby freeing up hospital beds on a busy med-surg floor. Patient visits
during "off hours" (nights and weekends) were three times more efficient than
conventional visits during these times (20 min per visit vs 40-min round trip
travel + 20-min visit). Patients and nursing personnel both expressed tremendous
satisfaction with the remote-presence interaction. CONCLUSIONS: The authors'
early experience suggests a significant benefit to patients, hospitals, and
physicians with the use of RP6. The implications for future development are
enormous.
PMID- 17031746
TI - HIDA scan ejection fraction does not predict sphincter of Oddi hypertension or
clinical outcome in patients with suspected chronic acalculous cholecystitis.
AB - BACKGROUND: Hepatobiliary iminodiacetic scan with ejection fraction (HIDA EF) is
used to evaluate chronic acalculous cholecystitis (CAC). A presumed etiology of
CAC is sphincter of Oddi hypertension (SOH). In this study, we evaluated the
value of HIDA EF to predict patient response to laparoscopic cholecystectomy and
to identify SOH. METHODS: A prospective study of 93 patients with biliary pain
but without gallstones (CAC) who underwent preoperative HIDA EF was conducted. At
laparoscopic cholecystectomy, transcystic antegrade biliary manometry was
performed to determine the SO pressure. Patients were evaluated postoperatively
for response to cholecystectomy. The sensitivity, specificity, positive
predictive value (PPV), and negative predictive value (NPV) were calculated. The
outcomes were compared with the clinical impression. RESULTS: Of the 93 patients
with both HIDA EF and SOP measurements, 50 had abnormal EF (< 35%); of these, 29
had SOH (SO pressure > or = 40 mmHg). Of the 43 patients with normal HIDA EF, 30
had SOH. The sensitivity was 49%, specificity 38%, PPV 58%, and NPV 30%. Eighty
six of the 93 patients returned for follow-up evaluation. Follow-up ranged from 0
to 99 months, with a mean of 26.4 months. Overall, 73 patients (85%) improved. Of
the 46 with abnormal HIDA EF, 42 (91%) improved. Of the 40 patients with normal
HIDA EF, 31 (77.5%) improved. The sensitivity was 57.7%, specificity 69.2%, PPV
91.3%, and NPV 22.5%. CONCLUSION: Although the PPV of abnormal HIDA EF is high,
it is not much better than the clinical impression. The sensitivity and
specificity are marginal. The NPV is poor. Based on the review of these 93
patients, HIDA EF is not reliable for identifying CAC. We recommend that patients
with normal HIDA EF have additional testing or consultation before ruling out
CAC. HIDA EF does not predict SOH.
PMID- 17031747
TI - Laparoscopic cholecystectomy for early gallbladder carcinoma: long-term outcome
in comparison with conventional open cholecystectomy.
AB - BACKGROUND: The role of laparoscopic surgery for malignant gallbladder tumors
remains uncertain. This study compared the surgical results of laparoscopic
versus conventional open cholecystectomy for patients with early-stage
gallbladder carcinoma and examined the role of laparoscopic surgery for early
gallbladder carcinomas. METHODS: Data for the treatment of gallbladder carcinomas
were gathered from Chang Gung Memorial Hospital (Linkou, Taiwan). A retrospective
analysis of 40 patients with either stage 0 or stage 1 gallbladder carcinoma was
performed. The patients were categorized into two groups on the basis of
cholecystectomy procedures. The long-term outcomes for the two groups were
compared. RESULTS: During the follow-up period, which ranged from 6.5 to 197.6
months, four patients in the conventional open cholecystectomy group encountered
tumor recurrence, and one patient in the laparoscopic cholecystectomy group
experienced distant tumor recurrence (p = 0.216). No local port-site tumor
recurrence was identified in patients who underwent laparoscopic cholecystectomy.
The overall 5-year survival rate in this series was 87.1%. A comparison of
survival rates between the two groups demonstrated no significant difference (p =
0.340). CONCLUSION: The laparoscopic cholecystectomy procedure did not adversely
influence the prognosis of patients with early-stage gallbladder carcinomas.
Furthermore, meticulous removal of gallbladders during laparoscopic surgery, in
which early gallbladder carcinoma can be managed successfully using laparoscopic
cholecystectomy, achieved a satisfactory surgical result and a low port-site
tumor recurrence rate.
PMID- 17031748
TI - A comparison of the effects of pneumoperitoneum and laparotomy on natural killer
cell mediated cytotoxicity and Walker tumor growth in Wistar rats.
AB - BACKGROUND: Surgical stress promotes impaired immunological function, which
contributes to tumor growth. Natural killer activity (NKA) has a protective role
in immunity to tumors. So, the aim of this experimental study was to assess tumor
growth and (NKA) after pneumoperitoneum and laparotomy. METHODS; Sixty male
Wistar rats were divided into three groups (anesthesia, CO2 pneumoperitoneum and
laparotomy) plus ten controls. All experimental animals were inoculated
subcutaneously with 8 x 105 Walker carcinosarcoma 256 cells. Animals were
sacrificed on 1st(POD1) and 8th (POD8) postoperative day. Tumors were excised and
weighed. RESULTS: On POD1 all animals had diminished NKA when compared to
controls; NKA after pneumoperitoneum was significantly greater than after
laparotomy. On POD8 all animals, except after laparotomy, reached NKA at controls
levels. Tumor weight was significantly greater after laparotomy when compared to
pneumoperitoneum. CONCLUSIONS: Pneumoperitoneum causes a less depressed NKA and
less tumor growth when compared to laparotomy.
PMID- 17031749
TI - Optimum view distance for laparoscopic surgery.
AB - BACKGROUND: Proper visualization of the surgical field without fatigue is
essential in laparoscopic surgery and reduces the risk of iatrogenic injuries.
One of the important factors influencing visualization is the viewing distance
between the surgeon and the monitor. This was the subject of the current
investigation. METHODS: For this study, 14 surgeons participated in experiments
designed to determine two working distances from a standard 34-cm (14 in.
diagonal) cathode ray tube (CRT) monitor: (a) the maximum view distance
permitting small prints of a near vision chart to be identified clearly by sight,
(b) and the minimum view distance (of a standard resolution chart) just short of
flicker, image degradation, or both. The range of the monitor optimal working
distance for laparoscopic surgery was extrapolated from these data sets. RESULTS:
The maximum view distance allowing identification of detail averaged 221 cm
(range, 166-302 cm). The mean minimal view distance short of flicker/image
degradation was 136 cm (range, 102-168 cm). The coefficient of variation for the
two view distances was almost identical (18% vs 17%, respectively), and a
frequency histogram confirmed the normality of the two data sets. Thus, for most
surgeons, the extrapolated monitor view distances for laparoscopic surgery using
a 14-in. diagonal (34-cm) monitor range from 139 to 303 cm (57-121 in.) for
maximal distance viewing and from 90 to 182 cm (36-73 in.) for close-up viewing
(i.e., a monitor optimal working distance ranging from 90 to 303 cm (36-121 in.).
CONCLUSIONS: For most surgeons operating from a 14-in. diagonal CRT monitor, both
the maximal and minimal (close-up) view distances are individually variable, but
the surgeon should never be farther than 3 m (10 ft) or less than 0.9 m (3 ft)
from the monitor. However, within limits, the maximal view distance increases
with increasing monitor size. The limit for close-up distance is 0.9 m,
irrespective of monitor size.
PMID- 17031750
TI - The long-term follow-up of patients with positive intraoperative cholangiograms
during laparoscopic cholecystectomy.
PMID- 17031751
TI - Induction of oxidative stress in erythrocytes of male rats subchronically exposed
to a mixture of eight metals found as groundwater contaminants in different parts
of India.
AB - Exposure of animals and humans to different metal components through contaminated
drinking water can result in a wide range of adverse clinical conditions.
Toxicological consequences arising from the concurrent repeated exposure to
multiple metal contaminants are not known. The purpose of the present study was
to evaluate the oxidative stress-inducing potential of a mixture of eight metals
(arsenic, cadmium, lead, mercury, chromium, nickel, manganese, iron),
representative of groundwater contamination in different areas of India, in
erythrocytes of male rats subchronically exposed to environmentally relevant
doses via drinking water. The selection of these metals, as determined by
literature survey of groundwater contamination in India, was primarily based on
the frequency of their occurrence and contamination level above World Health
Organization maximum permissible limit (MPL) in drinking water. Male albino
Wistar rats were exposed to the metal mixture at 0, 1, 10, and 100 times the mode
concentrations (the most frequently occurring concentration) of the individual
metals in drinking water for 90 days. In addition, one group of rats was also
exposed to the mixture at a concentration equal to the MPL of individual
components. The oxidative stress in erythrocytes was evaluated by assessing the
magnitude of malondialdehyde production and reduced glutathione (GSH) content and
the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase
(GPx), and glutathione reductase (GR) after 30, 60, and 90 days of exposure. MPL
and 1x dose levels did not cause any changes. The mixture at 10x and 100x doses
caused dose- and time-dependent effects. After 30 days, the 10x dose did not
cause any changes except increase in SOD activity. The 100x dose increased the
activities of SOD, catalase and GR and the GSH level, but caused no alterations
in lipid peroxidation (LPO) and GPx activity. After 60 days, the 10x dose did not
cause any changes. The 100x dose increased LPO and decreased all the antioxidant
parameters, except GSH. After 90 days, both 10x and 100x levels elevated LPO. The
10x dose decreased GSH level and activities of SOD and catalase, but not of GPx
and GR, whereas the 100x dose decreased all the antioxidative systems. Overall,
the present study demonstrates that the subchronic exposure of male rats to the
mixture of metals via drinking water results in induction of oxidative stress and
concomitant reduction in antioxidative defense system in erythrocytes at 10 and
100 times the mode concentrations of the individual metals in contaminated
groundwater.
PMID- 17031752
TI - Response of pepper plants (Capsicum annum L.) on soil amendment by inorganic and
organic compounds of arsenic.
AB - The influence of soil contamination by inorganic and organic arsenic compounds on
uptake, accumulation, and transformation of arsenic in pepper (Capsicum annum L.)
was investigated in greenhouse pot experiments under controlled conditions.
Pepper plants were cultivated in substrate amended by aqueous solutions of
arsenite, arsenate, methylarsonic acid (MA), and dimethylarsinic acid (DMA)
applied individually into cultivation substrate at concentrations of 15 mg As per
kg of substrate. The plant availability of the arsenicals increased in the order
arsenite = arsenate < MA < DMA. The highest arsenic concentrations were found in
roots followed by stems, leaves, and fruits regardless of arsenic compound
applied. In the control samples of pepper fruits, As(III), As(V), and DMA were
present (25%, 37%, and 39% of the water-extractable arsenic). In control stems +
leaves and roots, As(V) was the major compound (63% and 53% in a phosphate buffer
extract) followed by As(III) representing 33% and 42%. Additionally, low
concentrations (not exceeding 5%) of DMA and MA were detected as well. In all the
soils analyzed after the first harvest of pepper fruits, arsenate was the
dominating compound followed by arsenite. Methylarsonic acid, methylarsonous
acid, and DMA were present at varying concentrations depending on the individual
soil treatments. In the treated plants, the arsenic compounds in plant tissues
reflected predominantly the extractable portions of arsenic compounds present in
soil after amendment, and this pattern was more significant in the first part of
vegetation period. The results confirmed the ability of generative parts of
plants to accumulate preferably organic arsenic compounds, whereas in the roots
and aboveground biomass, mainly inorganic arsenic species are present. Evidently,
the source of soil arsenic contamination affects significantly the extractable
portions of arsenic compounds in soil and subsequently the distribution of
arsenic compounds within the plants.
PMID- 17031753
TI - 2,4-D butoxyethyl ester kinetics in embryos of Xenopus laevis: the role of the
embryonic jelly coat in reducing chemical absorption.
AB - The role of the jelly coat in providing a protective barrier to chemical
absorption was studied using the embryos of the amphibian, Xenopus laevis.
Embryos with or without a jelly coat were water exposed to the butoxyethyl ester
of 2,4-dichlorophenoxyacetic acid (2,4-D BEE) and the rates of uptake,
metabolism, distribution, and excretion were determined. The water uptake
clearance rates were slower for embryos with a jelly coat (1.5-4.5 ml(water).g
(embryo) (-1).h(-1) or 0.040-0.022 ml(water).h(-1) per embryo) in comparison to
dejellied embryos (14-21 ml(water).g (embryo) (-1).h(-1) 0.0066-0.021
ml(water).h(-1) per embryo). This accounted for the much lower residues in
embryos with a jelly coat than in dejellied embryos during 8 h of exposure.
Despite quantitative differences in uptake, once 2,4-D BEE had entered the
embryos, metabolism and distribution were similar between the two test groups.
2,4-D BEE was metabolized to 2,4-dichlorophenoxyacetic acid (2,4-D) with half
lives ranging from 35 to 42 minutes. The radioactive residues, as determined by
whole body autoradiography, appeared throughout the embryo with a slight
accumulation in the blastocoel. Furthermore, 35% of the radioactive residues were
located in the jelly coat and 65% in the developing embryo. Based on a slower 2,4
D elimination in embryos with a jelly coat, the diffusive properties that
decreased 2,4-D BEE uptake appeared to similarly decrease elimination of its
metabolite. The common practice of removing jelly coats prior to embryonic
amphibian toxicity studies, as in the widely used Frog Embryo Teratogenesis Assay
Xenopus (FETAX), is discouraged based on the kinetic differences observed in this
study.
PMID- 17031754
TI - Impact of waterborne copper on the structure of gills and hepatopancreas and its
impact on the content of metallothionein in juvenile giant freshwater prawn
Macrobrachium rosenbergii (Crustacea: Decapoda).
AB - This study aims to elucidate both the impact of copper on the structure of the
gills and hepatopancreas and the induction of metallothionein (MT) during
waterborne copper exposure in juvenile Macrobrachium rosenbergii. Structural
observations were performed with light microscopy, and the MT titrations were
performed with the cadmium saturation assay. The structural changes that occurred
in the gills and hepatopancreas appeared to result from copper accumulation, and
the degree of damage observed in both tissues was relevant to the elevated
waterborne copper concentration. Exposure to copper concentrations ranging from
0.01 mg/L to 0.4 mg/L for 7 days resulted in profound structural changes
including the accumulation of hemocytes in the hemocoelic space; swelling and
fusion of the lamellae; abnormal gill tips; and hyperplastic, necrotic, and
clavate-globate lamellae in the gills. Similarly, hemocytic infiltration in the
interstitial sinuses, an increased number of hemocytes, thickening and ruptures
of the basal laminae, and necrosis of the tubules were observed in the
hepatopancreas. The MT measurements showed no significant differences in MT
contents between the control group and the group treated with 0.01 mg/L
waterborne copper. The maximum MT content was observed at the level of 0.4 mg/L
waterborne copper.
PMID- 17031755
TI - Oxidative degradation of BPA using TiO2 in water, and transition of estrogenic
activity in the degradation pathways.
AB - The oxidative degradation behavior of bisphenol A (BPA) using titanium dioxide
(TiO(2)) in water was investigated. The main purposes were to clarify the
relationship with estrogenic activity from the degradation pathways demonstrated
by oxidation of BPA in water. Approximately 99% of the BPA decomposed within 300
min, and gas chromatography (GC) mass spectrometry (MS) and liquid chromatography
(LC) MS analysis revealed many intermediates during the degradation process.
Intermediates by decomposition of BPA, such as hydroxylated-BPA (OH-BPA),
carboxylic intermediates, phenolic intermediates, and other intermediates
produced by the cleavage of a benzene ring were identified and quantified.
Estrogenic activities of the degradation pathways of the BPA in water were
assessed by using a constructed yeast two-hybrid assay system for human estrogen
receptor alpha (hERalpha) and Japanese medaka fish (Oryzias latipes) estrogen
receptor alpha (medERalpha). Estrogenic activity for hERalpha and medERalpha was
reduced to less than 20% of the initial activity for BPA after 240 min of UV
irradiation. However, estrogenic activity for medERalpha was increased by 110%
from the initial activity for BPA at 60 min of UV irradiation. It was estimated
that medERalpha assay was more sensitive for BPA and the intermediates than was
the hERalpha assay. From these findings, we estimate that the intermediates by
the oxidation of BPA have the behaviors of xenoestrogen to the aquatic wildlife
in the environment.
PMID- 17031756
TI - Biosynthetic capacity of rainbow trout (Oncorhynchus mykiss) interrenal tissue
after cadmium exposure.
AB - The disruption of endocrine system function in wildlife species, including
teleosts, by contaminants such as metals is presently of major environmental
concern. Recently, it has been shown that cadmium (Cd) exposure results in
significant reductions in corticosteroid secretion by fish interrenal
steroidogenic cells, likely through an inhibition of intracellular cortisol
synthesis. In the present study, the effects of CdCl(2) on unstimulated and
stimulated interrenal steroidogenesis in rainbow trout were examined with the
intention of furthering an understanding of the site(s) of Cd toxic action.
CdCl(2) alone reduced cortisol secretion in minced interrenal tissues to 59% and
55% of control values when exposed to 10 and 100 microM, respectively. Incubation
of interrenal tissues with 0.01 IU/mL adrenocorticotropic hormone (ACTH), which
activates rate-limiting steps in steroid synthesis, resulted in significant
stimulation of steroidogenesis in controls. However, ACTH-stimulated
steroidogenesis was reduced when tissues were previously incubated with Cd.
Maximal rates of unstimulated cortisol secretion were achieved by augmentation
using 5 microM 25-hydroxycholesterol (25-OHC) or 0.8 microL/mL synthetic
cholesterol [SyntheChol(SC)]. Steroidogenesis augmentation by 25-OHC was
significantly reduced in tissues incubated with Cd. Interestingly, cortisol
secretion was significantly higher in SC-augmented tissue exposed to 1 and 10
microM Cd when compared to augmented control tissues. The results of this study
show that Cd affects both stimulated and unstimulated steroidogenesis in rainbow
trout, and that one major site(s) of action of Cd in the cortisol synthesis
pathway is likely prior to cytochrome P450 side chain cleavage.
PMID- 17031757
TI - Porcine reproductive and respiratory syndrome virus productively infects monocyte
derived dendritic cells and compromises their antigen-presenting ability.
AB - Dendritic cells (DC) are potent antigen-presenting cells that play an important
role in inducing primary antigen-specific immune responses. However, some viruses
have evolved to specifically target DC to circumvent the host's immune responses
for their persistence in the host. Porcine reproductive and respiratory syndrome
virus (PRRSV) causes a persistent infection in susceptible animals. Although it
is generally believed that the existence of PRRSV quasispecies is partly
responsible for the virus persistence, other mechanisms of immune evasion or
immune suppression may also exist. Here, we studied the role of DC in PRRSV
persistence and immune suppression. Our results showed that PRRSV underwent a
productive replication in pig monocyte-derived DC (Mo-DC) as measured by both
immunofluorescence staining of viral nucleocapsid protein and virus titration
assays, leading to cell death via both apoptosis and necrosis mechanisms.
Additionally, PRRSV infection of Mo-DC resulted in reduced expression of MHC
class I, MHC class II, CD14 and CD11b/c. This was in agreement with the impaired
mixed lymphocyte reaction of PRRSV-infected Mo-DC compared to that of mock
infected Mo-DC. We also examined the cytokine profiles of PRRSV-infected Mo-DC
using a quantitative ELISA method. Results indicated that no apparent change in
the levels of IL-10, IL-12 and IFN-gamma was detected. Taken together, our data
demonstrate that PRRSV productively infects Mo-DC and impairs the normal antigen
presentation ability of Mo-DC by inducing cell death, down-regulating the
expression of MHC class I, MHC class II, CD11b/c and CD14 and by inducing minimal
Th1 cytokines.
PMID- 17031758
TI - Effects of pravastatin on ventricular remodeling by activation of myocardial KATP
channels in infarcted rats: role of 70-kDa S6 kinase.
AB - Reactive cardiomyocyte hypertrophy after myocardial infarction is an important
risk factor for arrhythmias. Myocardial ATP-sensitive potassium (K(ATP)) channels
have been implicated in attenuating cardiac hypertrophy by inhibition of 70-kDa
S6 kinase. We investigated the effect of pravastatin on ventricular hypertrophy
during remodeling after myocardial infarction and whether the attenuated
hypertrophic effect was via activation of myocardial K(ATP) channels. Twenty-four
hours after ligation of the anterior descending artery, male Wistar rats were
randomized to either vehicle, nicorandil (an agonist of K(ATP) channels),
pravastatin, glibenclamide (an antagonist of K(ATP) channels), or a combination
of nicorandil and glibenclamide or pravastatin and glibenclamide for 4 weeks.
Infarct size and mortality were similar among the infarcted groups. Cardiomyocyte
sizes isolated by enzymatic dissociation after infarction significantly increased
at the border zone in vehicle-treated infarcted rats compared with sham-operated
rats. Rats in the nicorandil- and pravastatin-treated groups significantly
attenuated cardiomyocyte hypertrophy, as compared with the vehicle-treated group.
Arrhythmic scores during programmed stimulation mirrored those of cardiomyocyte
hypertrophy. Increased 70-kDa S6 kinase mRNA expression in cardiac remodeling was
confirmed by reverse transcription-polymerase chain reaction, consistent with the
results of immunohistochemistry and Western blot for the phosphorylation of 70
kDa S6 kinase. Nicorandil-induced effects were abolished by administering
glibenclamide. Similarly, the beneficial effects of pravastatin were abolished by
administering glibenclamide, implicating K(ATP) channels as the relevant target.
Activation of K(ATP) channels by pravastatin administration can attenuate
ventricular remodeling through a S6 kinase-dependent pathway after infarction.
PMID- 17031759
TI - [Hearing loss -- can heat shock protein 70 be cited as prognostic marker?].
PMID- 17031760
TI - [Tonsillectomy -- dexamethasone lessens postoperative pain].
PMID- 17031761
TI - [Problems of hyomandibulopexia in patients with OSAS].
AB - In cases of obstructive sleep apnea syndrome (OSAS) with intolerance of n-CPAP
(nasal continuous positive airway pressure) treatment, hyoidthyroidpexia
(synonym: hyoid suspension) has recently been advocated by some authors as a
valuable surgical option. Despite a basically positive assessment, there is a
risk of hindrance to the speaking and swallowing function. Moreover, the thyroid
cartilage seems to be too weak for fixation of the hyoid with its complex
muscular attachments. This reduces the likelihood of achieving positive long-term
results. Considering aspects of preserving laryngeal function, we are reporting
on 7 patients submitted to a hyomandibulopexia. This intervention counteracts the
tendency of the tongue base to collapse by ventrolateral traction on the
hypoglossal muscle via the severed greater horn of the hyoid. We have thus far
had to correct our surgical procedure three times because of methodological
problems in the postoperative phase. Specific problems with surgical materials
like steel wire or Goretex are discussed. In conclusion, we explain why we
consider a bone anchored Kevlar suture (FASTak of Arthrex) to be suitable for
this operation. Considering functional aspects, our polysomnographic and
phoniatric follow-up examinations point to a less traumatic surgical procedure
with promising treatment results.
PMID- 17031762
TI - [The rationale for imaging methods in head and neck oncology].
PMID- 17031763
TI - [Exostosis of the internal auditory canal in a patient with myotonic dystrophy].
AB - A 53-year-old patient with myotonic dystrophy presented to our clinic with
progressive bilateral hearing loss. The ENT status and particularly the
otological examination were without pathological signs. Pure tone audiograms
showed a bilateral moderate to severe sensorineural hearing loss. Routinely
performed computed tomography of the temporal bones revealed the rare picture of
exostosis of the internal auditory canals and the medial surface of the petrous
bones. To our knowledge, this is the first report describing exostosis of the
internal auditory canal in a patient with myotonic dystrophy, although at present
it remains unclear in how far there is a causal connection between these two
pathologies.
PMID- 17031764
TI - [Malignant external otitis].
AB - Malignant external otitis or skull base osteomyelitis and osteoradionecrosis of
the skull base and the skull are potentially life-threatening conditions. The
standard methods of treatment involve the use of antibiotics, local treatment
and, where necessary, surgical excision of necrotic tissue. These approaches do
not provide a complete cure in many cases. Severe functional deficits and even
death can occur in advanced stages. We conducted a long-term retrospective follow
up study and report on a multimodal approach that we have been using with great
success since 1987. The four cornerstones of this treatment are surgical
debridement, combinations of antibiotics, specific immunoglobulins, and
adjunctive hyperbaric oxygen therapy. This multimodal treatment approach has
proved to be highly effective in improving the survival and quality of life of
the patients concerned. These excellent outcomes justify the high costs that this
therapy admittedly involves.
PMID- 17031765
TI - [Standardization of the German short version of "profile of mood states" (POMS)
in a representative sample--short communication].
AB - The questionnaire "Profile of Mood States (POMS)" is recommended as a measure of
mood states in patients and non-clinical samples. On the basis of a
representative sample (2043 subjects) reference values for the four scales
(DEPRESSION/ANXIETY, FATIGUE, VIGOR, ANGER) of the German short version of the
"Profile of Mood States" (POMS--35 items, 7 point scale, instruction "How you
have been feeling during the past 24 hours?") are presented. The scale ANGER was
independent from variables gender, age, education and current residence. In
contrast to the other three scales these differentiations were necessary and
detailed reference values are reported.
PMID- 17031766
TI - [Gender mainstreaming: relevance for psychotherapeutic research and practice].
PMID- 17031767
TI - [Effects of psychosomatic interventions within the consultation service of a
gynecological university hospital].
AB - The influence of psychotherapeutic interventions on the long-term course of
anxiety and depression of inpatients of a Gynaecological University Hospital was
examined in a prospective naturalistic provision study. All patients admitted to
hospital within a year were examined regarding anxiety and depression (HADS). The
patients who had conspicuous values in their questionnaires were randomly
assigned to an intervention or a control group. There was a follow-up examination
for them one year after the first examination. In the first examination 715
participants took part, in the follow-up examination there were 429. Women with
malignant gynaecological diseases suffer more severely from anxiety (t=7.02;
p<0.001) and depression (t=3.87; p<0.001) in comparison with the normal
population. Women suffering from general gynaecological (t=7.75; p<0.001) and
obstetrical diseases (t=5.95; p<0.001) are significantly more anxious. Whereas
the anxiety in patients with general gynaecological (F=3.02; p=0.031) as well as
in patients with obstetrical diseases (F=3.52; p=0.017) can be reduced
significantly in the long-term by psychotherapeutic interventions, depression
cannot or only slightly be influenced. This shows that low-frequent
psychotherapeutic interventions with psycho-educative, supportive approaches (e.
g. in the framework of psychosomatic consultation and liaison service) have
positive effects on anxiety in the long run, whereas depression is to be
influenced rather by long-term interventions or classic depth-psychological or
behaviour therapeutic interventions.
PMID- 17031768
TI - [The influence of psychiatric comorbidity on the length of hospital stay of
medical inpatients within the German Diagnosis Related Groups System].
AB - The influence of psychiatric comorbidity (ICD-10 categories F1, F3, F4 and F5) on
the length of hospital stay of 4936 medical inpatients of two medical departments
of a hospital of tertiary care level was studied. In 994/4936 patients (20.2%) at
least one F (1,3,4,5)-diagnosis had been coded. 160/994 patients (16.1%) had
undergone psychosomatic consultation (CL) service treatment. The median of the
time of from admission until first contact with CL-service was 3 days. Patients
with psychiatric comorbidity had a significant longer hospital stay (median stay
without CL-service 5 days, with CL-service 8 days) than patients with no F
diagnoses coded (4 days) (p<0.01). There were no differences as to patient
complication and complexity level PCCL between the three groups. Even within a
diagnosis related groups system psychiatric comorbidity has a negative effect on
the length of hospital stay.
PMID- 17031769
TI - [Changes in alexithymia and emotional awareness during psychotherapeutic
inpatient treatment].
AB - The aim of the study was to investigate whether alexithymia and emotional
awareness could be improved by psychotherapeutic inpatient treatment. The role of
alexithymia and emotional awareness in predicting the treatment outcome was
investigated. 48 psychosomatically ill patients completed German versions of the
Toronto Alexithymia Scale (TAS-20), the Levels of Emotional Awareness Scale
(LEAS), the Symptom Check List (SCL-90-R), the Global Assessment Scale of
Function (GAF) and the "Beeintrachtigungs-Schwere-Score" (BSS) to assess the
severity of patient psychological impairment. Psychotherapeutic inpatient
treatment was associated with a decrease in alexithymia as measured by TAS-20.
The expected improvement of emotional awareness failed to be statistically
significant. This may be due to the smaller retest reliability of the LEAS. High
scores in emotional awareness before therapy as measured by LEAS emerged as a
predictor of successful psychotherapy with respect to GAF.
PMID- 17031770
TI - [Depersonalization, social phobia and shame].
AB - Associations between depersonalization (DP) and social phobia (SP) were described
in the early scientific literature. This connection, however, has not yet been
considered in the recent empirical literature and clinical trials on SP. The aim
of this study is to examine these associations. In a sample of 100 consecutive
inpatients we compare 45 patients with pathological DP to 55 patients without
pathological DP with respect to comorbidity and the degree of social anxieties
assessed with the SOCIAL INTERACTION ANXIETY SCALE (SIAS) and with the SOCIAL
PHOBIA SCALE (SPS) and the extent of shame assessed with the INTERNALIZED SHAME
SCALE (ISS). Social phobia was significantly more prevalent in the patients with
pathological DP. Furthermore, the patients with pathological DP showed a
significantly larger extent of social anxieties (SIAS, SPS) and shame (ISS). The
results may be considered as a preliminary empirical support of the assumed
associations and thus warrant an enhanced consideration of DP in therapy and
research of social anxiety disorders.
PMID- 17031771
TI - [Has the translation process impact on the psychometric structure of a
questionnaire?].
AB - Little is known about the impact of item translation on the psychometric
structure of questionnaires. The analysis of different translation versions
within the same language provides an opportunity to address this question.
Therefore, in the present study, two of the six available German translations of
Eating Disorder Inventory (EDI) were compared with respect to their psychometric
structure. A total of 449 female students completed the short forms of the EDI
(consisting of the subscales drive for thinness, bulimia and body
dissatisfaction). Structural equation modeling revealed that the item contents in
both translations had been interpreted equivalently by the participants. In
addition, the structural relations among the factors were equivalent across both
versions. Whereas invariance of item-pair reliability was not tenable, the
distribution of raw scores of the scales was similar. All in all, the findings
suggest a very large degree of similarity in the psychometric structure of the
alternative translations of the EDI versions. The results are discussed with
respect to the lack of standards for the translation of questionnaires.
PMID- 17031772
TI - [Development and psychometric evaluation of the "Freiburg questionnaire--stages
of change in tinnitus" (FQ-STATI)].
AB - This study describes the psychometric development of an instrument to measure the
"stages of change" in tinnitus sufferers. Based on our own previous work about
measuring stages of change in chronic pain patients, 48 items were administered
to 128 tinnitus sufferers in inpatient and outpatient facilities as well as in
self helping groups. Principle component analysis and item analysis led to a four
factor solution. Each factor (resp. stage) consisted of four items:
precontemplation, preparation, action, and termination. Scales showed
theoretically conformed associations with measure of pain burden e. g. tinnitus
loudness and cumbersomeness as well with standardized measures (HADS, TB-12, SF
12). High burden was correlated positively with high expressions on the lower
scales, and it was correlated negatively with higher stage scores. Against the
assumption there was no association between tinnitus durability and stages
expression.
PMID- 17031773
TI - [Readiness for behavioural change in somatoform disorders].
AB - The readiness for behavioural change in patients with somatoform symptoms
constitutes an important construct in psychotherapy research. However, no
psychometric instrument is available yet for assessing this construct. This
study, therefore, attempts to adapt a questionnaire for the assessment of the
"readiness for behavioural change" in patients with chronic pain (FQ-STAPM) to
patients with somatoform symptoms. Various psychometric test criteria of the
questionnaire are examined. The sample consists of n=103 in- and outpatients with
multiple somatoform symptoms. Item characteristics, reliability (internal
consistency), and construct validity for three of the four adapted scales are
acceptable. Furthermore, the four-factor-structure of the FQ-STAPM can be
confirmed. Moderate changes on the adapted scales of the FQ-STAPM are detected in
a longitudinal design. The results corroborate the applicability of the
instrument in patients with somatoform symptoms.
PMID- 17031774
TI - [The predictive quality of the Psychopathy Checklist-Revised (PCL-R) for violent
and sex offenders in Switzerland. A validation study].
AB - In Switzerland, the Hare Psychopathy Checklist-Revised (PCL-R) is administered
rather restrictively for risk assessment of recidivism among violent and sexual
offenders. The aim of the present study was a first-time evaluation of the
predictive validity of the PCL-R for violent and sexual recidivism in
Switzerland. The PCL-R scores of 96 violent and sex offenders were evaluated by
collecting the data in their psychiatric expert opinions. The scores were then
compared to the rates of recidivism as shown in the criminal records. Consistent
with previous studies in North America and Europe, the determined predictive
accuracy was satisfying. This degree of precision supports the use of the PCL-R
for risk assessment of sexual and violent recidivism in Switzerland, as long as
the instrument does not constitute the sole criterion to determine future
recidivism, but is applied only in combination with a thorough clinical
evaluation. The use of precise cut-off scores did not prove to be a valid
criterion for the prognosis of recidivism and can therefore not be recommended
for Swiss offenders.
PMID- 17031776
TI - [Selective serotonine reuptake inhibitors (SSRI) in the treatment of paraphilia].
AB - For about 15 years selective serotonine reuptake inhibitors (SSRI) have been used
in the treatment of paraphilias. In an open, uncontrolled, retrospective study,
which was the first in the German speaking countries we investigated 16 male
outpatients, who have been treated for different paraphilias with SSRI and
psychotherapy. There was a marked reduction in paraphilic symptoms. Despite high
rates of sexual side effects most patients reported a high overall treatment
satisfaction. SSRI are an important addition in pharmacological treatment of
paraphilic patients, especially with a risk of so called "hands-off" delinquency.
PMID- 17031775
TI - [Mixed episodes in bipolar disorder: a review].
AB - Affective mixed states in bipolar disorders are a current matter of scientific
debate and represent a complex clinical picture with coexisting manic and
depressive symptoms. Treatment of mixed states is regarded as an important
challenge. As diagnostic uncertainties complicate systematic clinical evaluations
of this patient group, generally accepted clinical treatment guidelines are
lacking yet. In this review the significance as well as the problems and risks of
new treatment options are discussed.
PMID- 17031777
TI - [Neurobiological mechanisms and pharmacological treatment options for alcohol
craving].
AB - In the last years, numerous studies have been performed on neurobiological
mechanisms in alcohol craving. Changes in the hypothalamic cortisol pathway and
the leptin metabolism, which is also associated with pharmacological
interventions, have been of special interest. With acamprosate and naltrexone two
substances exist for pharmacotherapy, but recent results about the efficacy are
controversial. The clinical profit of disulfiram has been shown, at least in a
subgroup of patients. Besides, there are several promising candidate substances.
Current investigations focus on a differentiated pharmacotherapy of alcohol
dependence, including psychological and genetic factors.
PMID- 17031778
TI - [Psychiatric expert opinion in case of early retirement--how reliable?].
AB - The study provides first data on reliability of expert psychiatric opinion under
regulations of the German state run pension scheme. 22 experienced psychiatrists
judged very heterogeneously on a hypothetical case suffering from recurrent
depression of moderate severity. Diagnosis according to ICD-10 led to six
different diagnoses. 32 % produced the most probable ICD-10 diagnosis, 86 % a
second diagnosis and 32 % a third. In their final socio-medical verdict eight
experts found an early retirement on medical grounds to be unjustified, four
experts thought the insured member incapable of working at all and ten believed
she was able to work 4-6 hours a day. Contrary to wide held believes concerning
"lax" psychiatric experts our sample revealed the experts to be "tough". This
high variability of expert opinions is, however, unacceptable for members of the
German state-run pensions schemes.
PMID- 17031779
TI - Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected
ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis
of SARS.
AB - The authors have previously shown that acute lung injury (ALI) produces a wide
spectrum of pathological processes in patients who die of severe acute
respiratory syndrome (SARS) and that the SARS coronavirus (SARS-CoV)
nucleoprotein is detectable in the lungs, and other organs and tissues, in these
patients. In the present study, immunohistochemistry (IHC) and in situ
hybridization (ISH) assays were used to analyse the expression of angiotensin
converting enzyme 2 (ACE2), SARS-CoV spike (S) protein, and some pro-inflammatory
cytokines (PICs) including MCP-1, TGF-beta1, TNF-alpha, IL-1beta, and IL-6 in
autopsy tissues from four patients who died of SARS. SARS-CoV S protein and its
RNA were only detected in ACE2+ cells in the lungs and other organs, indicating
that ACE2-expressing cells are the primary targets for SARS-CoV infection in vivo
in humans. High levels of PICs were expressed in the SARS-CoV-infected ACE2+
cells, but not in the uninfected cells. These results suggest that cells infected
by SARS-CoV produce elevated levels of PICs which may cause immuno-mediated
damage to the lungs and other organs, resulting in ALI and, subsequently, multi
organ dysfunction. Therefore application of PIC antagonists may reduce the
severity and mortality of SARS.
PMID- 17031780
TI - Risk adjusted resource utilization for AMI patients treated in Japanese
hospitals.
AB - Though risk adjustment is necessary in order to make equitable comparisons of
resource utilization in the treatment of acute myocardial infarction patients,
there is little in the literature that can be practically applied without access
to clinical records or specialized registries. The aim of this study is to show
that effective models of resource utilization can be developed based on
administrative data, and to demonstrate a practical application of the same
models by comparing the risk-adjusted performance of the hospitals in our
dataset. The study sample included 1748 AMI cases discharged from 10 large,
private teaching hospitals in Japan, between 10 April 2001 and 30 June 2004.
Explanatory variables included procedures (CABG and PCI), length of stay,
outcome, patient demographics, diagnosis and comorbidity status. Multiple linear
regression models constructed for the study were able to account for 66.5, 27.7,
and 58.4% of observed variation in total charges, length of stay and charges per
day, respectively. The performance of models constructed for this study was
comparable to or better than performance reported by other studies that made use
of explanatory variables extracted from clinical data. The use of administrative
data in risk adjustment makes broad scale application of risk adjustment
feasible.
PMID- 17031781
TI - The economic cost of teen drinking: late graduation and lowered earnings.
AB - This paper analyzes the effect that binge drinking has on the probability of
graduating on time from high school and on future earnings. The analysis is
conducted on students in their senior year of high school using data from the
National Longitudinal Survey of Youth 1979. Importantly, the usual instruments
used to correct for the endogeneity of the drinking variable are found to be
robust only for women. This paper finds that heavy drinking decreases the
probability of graduating on time. Binge drinking does not have a direct impact
on adults' labor earnings, but graduating late results in lower labor income.
Because of a late graduation, young men who binge in high school will face an
earnings penalty of 1.5-1.84 percentage points. Women also face a penalty, but
this seems mostly due to the fact that women who graduate late work in industries
and occupations that pay less.
PMID- 17031782
TI - Consolidations and closures: an empirical analysis of exits from the hospital
industry.
AB - This paper investigates the pre-exit characteristics of hospital mergers,
acquisitions, and closures. We estimate competing risk hazard models using an 18
year national data set that spans the wave of closures in the 1980s and of
mergers in the 1990s. Evidence shows that weak productivity of the hospital is a
strong determinant for closures while competitive pressures are more influential
in the decision to consolidate. Thus, increased market power, relative to cost
reductions, appears to play a larger role in the merger decision. Our results
also provide insight into possible correlations between mergers and closures.
PMID- 17031784
TI - What is the future of electrophoresis in large-scale genomic sequencing?
AB - Although a finished human genome reference sequence is now available, the ability
to sequence large, complex genomes remains critically important for researchers
in the biological sciences, and in particular, continued human genomic sequence
determination will ultimately help to realize the promise of medical care
tailored to an individual's unique genetic identity. Many new technologies are
being developed to decrease the costs and to dramatically increase the data
acquisition rate of such sequencing projects. These new sequencing approaches
include Sanger reaction-based technologies that have electrophoresis as the final
separation step as well as those that use completely novel, nonelectrophoretic
methods to generate sequence data. In this review, we discuss the various
advances in sequencing technologies and evaluate the current limitations of novel
methods that currently preclude their complete acceptance in large-scale
sequencing projects. Our primary goal is to analyze and predict the continuing
role of electrophoresis in large-scale DNA sequencing, both in the near and
longer term.
PMID- 17031786
TI - Microchips and single-photon avalanche diodes for DNA separation with high
sensitivity.
AB - Modern techniques for DNA and protein analysis and separation rely on
measurements of LIF and face a trend toward employing progressively smaller
samples. The currently employed detectors that provide the required ultrahigh
sensitivity, e.g. photomultiplier tubes (PMTs), are bulky and/or costly and
delicate, whereas a key issue for the development of compact and economical
instruments is the availability of miniaturized, inexpensive, and ultrasensitive
photodetectors. The planar epitaxial silicon single-photon avalanche diodes
(SPADs) combine the typical advantages of microelectronics (miniaturization,
ruggedness, low voltage, low power, low cost, etc.) with high sensitivity, even
better than that of PMTs. The suitability of such SPADs to microchip CE has been
here ascertained by developing a new apparatus with dual-wavelength LIF
detection. The apparatus has been experimented in studies on the EOF suppression
and on the coating stability and tested in rapid sizing of DNA fragments. The
experimental results obtained in the separation of Cy5-labeled oligonucleotide
demonstrate sensitivity better than 3 pM, which corresponds to less than 100
fluorescent molecules in the 50 pL illuminated volume.
PMID- 17031787
TI - The potential of electrophoretic mobility shift assays for clinical mutation
detection.
AB - As the understanding of the links between genetic mutations and diseases
continues to grow, there is an increasing need for techniques that can rapidly,
inexpensively, and sensitively detect DNA sequence alterations. Typically, such
analyses are performed on PCR-amplified gene regions. Automated DNA sequencing by
capillary array electrophoresis can be used, but is expensive to apply to large
numbers of patient samples and/or large genes, and may not always reveal low
abundance mutations in heterozygous samples. Many different types of genetic
differences need to be detected, including single-base substitutions and larger
sequence alterations such as insertions, deletions, and inversions.
Electrophoretic mobility shift assays seem well suited to this purpose and could
be used for the efficient screening of patient samples for sequence alterations,
effectively reducing the number of samples that must be subjected to full and
careful sequencing. While there is much promise, many of the mobility shift
assays presently under development have yet to be demonstrated to have the high
sensitivity and specificity of mutation detection required for routine clinical
application. Hence, further studies and optimization are required, in particular
the application of these methods not only to particular genes but also to large
numbers of patient samples in blinded studies aimed at the rigorous determination
of sensitivity and specificity. This review examines the state-of-the-art of the
most commonly used mobility shift assays for mutation detection, including
denaturing gradient gel electrophoresis, TGGE, SSCP, heteroduplex analysis, and
denaturing HPLC.
PMID- 17031791
TI - Orbitrap mass analyzer--overview and applications in proteomics.
AB - The orbitrap mass analyzer is proving itself as a useful addition to a proteomics
tool box. The key attributes of this analyzer are accurate mass and high
resolution similar to those achievable with FT ICR instrumentation. The basic
principles underlying these capabilities, and how they translate into benefits in
real-life proteomics experiments are discussed. The focus is on reviewing
examples of protein identification with bottom-up and top-down approaches, and
detection of post-translational modifications.
PMID- 17031793
TI - Web-based MS/MS data analysis.
AB - This tutorial focuses on three MS/MS data analysis programs currently available
via a web interface: Mascot, Phenyx and X!Tandem. Although these programs process
the same input and often produce comparable outputs, subtle differences remain.
The use of parameters that are requested in the on-line forms and the subsequent
interpretation of results are illustrated and explained via a single example.
PMID- 17031794
TI - The HUPO proteomics standards initiative--overcoming the fragmentation of
proteomics data.
AB - Proteomics is a key field of modern biomolecular research, with many small and
large scale efforts producing a wealth of proteomics data. However, the vast
majority of this data is never exploited to its full potential. Even in publicly
funded projects, often the raw data generated in a specific context is analysed,
conclusions are drawn and published, but little attention is paid to systematic
documentation, archiving, and public access to the data supporting the scientific
results. It is often difficult to validate the results stated in a particular
publication, and even simple global questions like "In which cellular contexts
has my protein of interest been observed?" can currently not be answered with
realistic effort, due to a lack of standardised reporting and collection of
proteomics data. The Proteomics Standards Initiative (PSI), a work group of the
Human Proteome Organisation (HUPO), defines community standards for data
representation in proteomics to facilitate systematic data capture, comparison,
exchange and verification. In this article we provide an overview of PSI
organisational structure, activities, and current results, as well as ways to get
involved in the broad-based, open PSI process.
PMID- 17031795
TI - Minimum reporting requirements for proteomics: a MIAPE primer.
AB - Amongst other functions, the Human Proteome Organization's Proteomics Standards
Initiative (HUPO PSI) facilitates the generation by the proteomics community of
guidelines that specify the appropriate level of detail to provide when
describing the various components of a proteomics experiment. These guidelines
are codified as the MIAPE (Minimum Information About a Proteomics Experiment)
specification, the first modules of which are now finalized. This primer
describes the structure and scope of MIAPE, places it in context amongst
reporting specifications for other domains, briefly discusses related informatics
resources and closes by considering the ramifications for the proteomics
community.
PMID- 17031796
TI - Comments on standards in proteomics and the concept of fitness-for-purpose.
PMID- 17031797
TI - Statistics for proteomics: a review of tools for analyzing experimental data.
AB - Most proteomics experiments make use of 'high throughput' technologies such as 2
DE, MS or protein arrays to measure simultaneously the expression levels of
thousands of proteins. Such experiments yield large, high-dimensional data sets
which usually reflect not only the biological but also technical and experimental
factors. Statistical tools are essential for evaluating these data and preventing
false conclusions. Here, an overview is given of some typical statistical tools
for proteomics experiments. In particular, we present methods for data
preprocessing (e.g. calibration, missing values estimation and outlier
detection), comparison of protein expression in different groups (e.g. detection
of differentially expressed proteins or classification of new observations) as
well as the detection of dependencies between proteins (e.g. protein clusters or
networks). We also discuss questions of sample size planning for some of these
methods.
PMID- 17031798
TI - Preparation of plant samples for 2-d electrophoresis.
AB - Plant protein samples are very difficult to extract and prepare for 2-D
electrophoresis, because polyphenols can build irreversible complexes with the
proteins, the protein concentrations are relatively low, polysaccharides and
lipids can cause severe disturbances in the 2-D gel.
PMID- 17031799
TI - Analysis of membrane protein complexes by blue native PAGE.
AB - Blue native polyacryamide gel electrophoresis is a special case of native
electrophoresis for high resolution separation of enzymatically active protein
complexes from tissue homogenates and cell fractions. The method is powerful
between 10 and 10,000 kDa. Also membrane protein complexes are separated well
after solubilization of complexes with mild neutral detergents. The separation
principle relies on binding of Coomassie blue G250 which provides negative
charges to the surface of the protein. During migration to the anode, protein
complexes are separated according to molecular mass and/or size and high
resolution is obtained by the decreasing pore size of a polyacrylamide gradient
gel. The principles of 2-dimensional blue native sodium dodecyl sulfate
polyacrylamide gel electrophoresis are presented here together with a practical
step-by-step guide to performing the method in the laboratory.
PMID- 17031800
TI - Sensitive, quantitative, and fast modifications for Coomassie Blue staining of
polyacrylamide gels.
AB - In spite of the high sensitivity of silver staining and the wide dynamic range of
various fluorescent detection methods, Coomassie Brilliant Blue staining is still
the most widely used protein detection technique for proteins separated by
polyacrylamide gel electrophoresis. There are several reasons: Low price, Visible
with the eye, Desk top scanners can be employed for image acquisition, Better for
quantitative analysis than silver staining, Possible modifications for fast or
highly sensitive staining, Mass spectrometry compatible.
PMID- 17031801
TI - Proteomics success story. Towards early detection of breast and ovarian cancer:
plasma proteomics as a tool to find novel markers.
PMID- 17031802
TI - Proteomics success story. Novel biomarkers for DNA damage response pathways:
insights and applications for cancer therapy.
PMID- 17031803
TI - Geographical focus. Proteomics initiatives in Spain: ProteoRed.
AB - The Spanish National Network of Proteomic Facilities--ProteoRed has been created
as an initiative for the coordination, integration and development of the
proteomics facilities and laboratories distributed throughout Spain. ProteoRed's
main objective is to give support to the scientific community allowing them wide
access to emerging proteomics technologies and thus encouraging the science of
proteomics. In addition, standardization of protocols and robustness of workflows
are addressed by multi-centric laboratory activities. Educational, training and
dissemination issues are part of the core activities of ProteoRed. To reach these
objectives, specific activities have been developed through six working groups
(WG1-WG6) covering functional, technical, educational and scientific aspects of
proteomics.
PMID- 17031804
TI - Report. Proteomics education, an important challenge for the scientific
community: report on the activities of the EuPA Education Committee.
AB - The main missions of the EuPA Education Committee (EuPA-EC) are to promote and
enhance the quality of proteomics knowledge by creating educational programs and
to initiate European-wide scientific exchange programs for young proteomics
researchers. In this first report we present the initial actions we have
undertaken in relation to the missions of the EuPA-EC, and the educational
activities that have been planned for 2007-2008. These activities include courses
(basic and advanced courses and a summer school), workshops, laboratory
networking and tutorials.
PMID- 17031805
TI - Random control clinical trial on the effects of aerobic exercise training on
erythrocyte levels during radiation treatment for breast cancer.
AB - BACKGROUND: Erythrocyte changes from aerobic exercise training were examined
during radiation treatment of breast cancer. METHODS: Twenty sedentary females
with breast carcinoma who were ages 35 to 65 years were randomized to aerobic
exercise (AE) of walking for 20 to 45 minutes, 3 to 5 times per week, at 50% to
70% of measured maximum heart rates or to placebo stretching (PS) activities 3 to
5 days per week during 7 weeks of radiation treatment. Measures were obtained 1
week before and after the radiation regimen. Serum blood analyses, through
complete blood counts, measured red blood cell counts (RBC), hematocrit (HCT),
and hemoglobin (HB). Peak aerobic capacity (peak VO(2)) was measured by exercise
testing with oxygen uptake analysis to assess training. A Wilcoxon Mann-Whitney U
test examined changes between groups (P < or = .05 for significance). RESULTS: AE
peak VO(2) increased by 6.3% (P = .001) and PS decreased by 4.6% (P = .083). RBC
increased in AE from 4.10 to 4.21 million cells/microL and declined in PS from
4.30 to 4.19 million cells/microL; the between-group differences were significant
(P = .014). HCT increased in AE from 38.0% to 38.8% and declined in PS from
37.40% to 36.50%; the between-group differences were significant (P = .046). HB
increased in AE from 12.3 to 12.4 g/dL and declined in PS from 12.25 to 11.77
g/dL; the between-group differences were significant (P = .009). CONCLUSIONS: The
results of the current study suggest that moderate intensity aerobic exercise
appears to maintain erythrocyte levels during radiation treatment of breast
cancer compared with the declines observed in nontraining individuals. These
findings suggest a safe, economical method to improve fitness and maintain
erythrocytes in women during radiation treatment of breast cancer.
PMID- 17031806
TI - Flores hominid: new species or microcephalic dwarf?
AB - The proposed new hominid "Homo floresiensis" is based on specimens from cave
deposits on the Indonesian island Flores. The primary evidence, dated at
approximately 18,000 y, is a skull and partial skeleton of a very small but
dentally adult individual (LB1). Incomplete specimens are attributed to eight
additional individuals. Stone tools at the site are also attributed to H.
floresiensis. The discoverers interpreted H. floresiensis as an insular dwarf
derived from Homo erectus, but others see LB1 as a small-bodied microcephalic
Homo sapiens. Study of virtual endocasts, including LB1 and a European
microcephalic, purportedly excluded microcephaly, but reconsideration reveals
several problems. The cranial capacity of LB1 ( approximately 400 cc) is smaller
than in any other known hominid < 3.5 Ma and is far too small to derive from Homo
erectus by normal dwarfing. By contrast, some associated tools were generated
with a prepared-core technique previously unknown for H. erectus, including
bladelets otherwise associated exclusively with H. sapiens. The single European
microcephalic skull used in comparing virtual endocasts was particularly
unsuitable. The specimen was a cast, not the original skull (traced to
Stuttgart), from a 10-year-old child with massive pathology. Moreover, the
calotte does not fit well with the rest of the cast, probably being a later
addition of unknown history. Consideration of various forms of human microcephaly
and of two adult specimens indicates that LB1 could well be a microcephalic Homo
sapiens. This is the most likely explanation for the incongruous association of a
small-brained recent hominid with advanced stone tools.
PMID- 17031807
TI - The anatomical record: a tradition of reporting what is new about things that are
very, very old.
PMID- 17031808
TI - Terminal nerve in the mouse-eared bat (Myotis myotis): ontogenetic aspects.
AB - As in other mammals, ontogenesis of the terminal nerve (TN) in the mouse-eared
bat (Myotis myotis) starts shortly after the formation of the olfactory placode,
a derivative of the ectoderm. During development of the olfactory pit,
proliferating neuroblasts thicken the placodal epithelium and one cell population
migrates toward the rostroventral tip of the telencephalon. Here they accumulate
in a primordial terminal ganglion, which successively divides into smaller units.
Initial fibers of the TN can be distinguished from olfactory fibers in the mid
embryonic period. The main TN fiber bundle (mfb) originates from the anteriormost
ganglion in the nasal roof, whereas one or more inconstant smaller fiber bundles
(sfb) originate from one or more smaller ganglia in the basal part of the rostral
nasal septum. The fibers of the mfb and sfbs join in the posterior quarter of the
nasal roof before reaching the central ganglion (M) located in the meninges
medial to the olfactory bulb. From the mid-fetal period onward, a thin TN fiber
bundle with some intermingled perikarya connects M to the brain by penetrating
its wall rostral to the olfactory tubercle. Additional smaller ganglia may occur
in this region. The TN and its ganglia persist in postnatal and adult bats but
the number of perikarya is reduced here. Moreover, the different potential
functions of the TN are discussed briefly.
PMID- 17031809
TI - Tissue evidence of the testosterone role on the abnormal growth and aging effects
reversion in the gerbil (Meriones unguiculatus) prostate.
AB - Prostate differentiation during embryogenesis and its further homeostatic state
maintenance during adult life depend on androgens. Abundant biological data
suggest that androgens play an important role in the development of the prostate
cancer and other prostatic diseases. The objective of this work was to evaluate
the effects of the testosterone supplementation in gerbil (a new experimental
model) at different ages. Tissues from experimental animals were studied by
histological and histochemistry procedures, androgen receptor
immunohistochemistry assay, morphometric-stereological analysis, and transmission
electron microscopy (TEM). After the treatment were observed increase of prostate
weight and epithelium height in all ages studied. In some adult and aged treated
animals, hyperplasic and dysplastic process were observed, including prostatic
intraepithelial neoplasias and adenocarcinomas. Increase of the thickness of the
smooth muscle cell (SMC) layer was observed in pubescent and adult animals and
TEM revealed apparent SMC hypertrophy. An apparent increase in the frequency of
blood vessels distributed by the subepithelial stroma in the treated animals was
noticed. Reversion of the natural effects of aging on the prostate was observed
in the aged treated animals in some acini of the gland. These data demonstrate
that the gerbil prostate is susceptible to androgenic action at the studied ages
and it can serve, for example, as experimental model to studies of prostate
neoplastic process induction and hormonal therapy in aged animals.
PMID- 17031810
TI - Three-dimensional myoarchitecture of the bovine tongue demonstrated by diffusion
spectrum magnetic resonance imaging with tractography.
AB - The anatomy of the mammalian tongue consists of an intricate array of variably
aligned and extensively interwoven muscle fibers. As a result, it is particularly
difficult to resolve the relationship between the tongue's microscopic anatomy
and tissue-scale mechanical function. In order to address this question, we
employed a method, diffusion spectrum imaging (DSI) with tractography, for
displaying the macroscopic orientational properties of the tissue's constituting
myofibers. DSI measures spatially variant proton displacement for a given 3D
imaging segment (voxel), reflecting the principal orientation(s) of its
myofibers. Tractography uses the angular similarity displayed by the principal
fiber populations of multiple adjacent voxels to generate tract-like structures.
DSI with tractography thus defines a unique set of tracts based on the net
orientational behavior of the myofiber populations at different positions in the
tissue. By this approach, we demonstrate a novel myoarchitectural pattern for the
bovine tongue, consisting of short and orthogonally aligned crossing fiber tracts
in the intrinsic core region, and longer, parallel-aligned fiber tracts on the
tissue margins and in the regions of extrinsic fiber insertion. The
identification of locally aligned myofiber populations by DSI with tractography
allows us to reconsider lingual anatomy, not in conventional microscopic terms,
but as a set of heterogeneously aligned and macroscopically resolved myofiber
tracts. We postulate that the properties associated with these myofiber tracts
predict the mechanical behavior of the tissue and thus constitute a method to
relate structure and function for anatomically complex muscular tissues.
PMID- 17031811
TI - Endochondral ossification of the mouse nasal septum.
AB - Endochondral ossification at the caudal junctions of the cartilaginous nasal
septum, in combination with interstitial expansion of the septum, is thought to
displace the facial skeleton away from the neurocranium. However, the rate of
endochondral ossification has not been measured or related to rates of septal
enlargement. This study examined endochondral ossification at these junctions in
mice from postnatal days 0-15, in the context of known cranial growth sites, the
synchondroses. BrdU labeling was used to compare cell division at the
septoethmoidal and septopresphenoidal junctions with cell division at the
synchondroses, and double-fluorochrome labeling was used to measure
mineralization rate. The results showed that the septoethmoidal and
septopresphenoidal junctions develop the characteristic morphology of growth
plates postnatally, and that the pattern of cell division is similar to that of
synchondroses. Mineralization at these junctions occurred at rates that were not
statistically different from those of the synchondroses. However, the
cartilaginous septum increased in length much more rapidly than could be
explained by caudal growth, implying that interstitial expansion is the more
important contributor to septal growth.
PMID- 17031812
TI - Distinctive localization of N- and E-cadherins in rat anterior pituitary gland.
AB - In the rat anterior pituitary gland, folliculo-stellate cells aggregate
preferably to form pseudofollicles, and each type of hormone-producing cell shows
adhesive affinity with particular types of heterologous hormone-producing cells.
Distribution of cadherin types in the rat anterior pituitary was examined
immunohistochemically to clarify the unique cell arrangements caused by
homologous and heterologous affinities among cells. N- and E-cadherins were
detected continuously along cell membranes, while P-cadherin was not. N- and E
cadherins showed distinct isolation in localization, with N-cadherins localized
in hormone-producing cells of distal and intermediate lobes in various amounts,
and E-cadherins limited to folliculo-stellate cells and marginal layer cells
facing the residual lumen of Rathke's pouch. A similar distribution of cadherins
was observed in cell clusters of primary cultured anterior pituitary cells. These
findings suggest that differential expression of cell adhesion molecules may be
partially responsible for localization of hormone-producing cells and folliculo
stellate cells.
PMID- 17031813
TI - In vivo imaging of prostate cancer involving bone in a mouse model.
AB - BACKGROUND: We compared the abilities of clinically relevant imaging modalities
to quantify prostate cancer involving bone in a mouse model. Such non-invasive
methods are needed pre-clinically to understand tumor biology and to evaluate
therapy. METHODS: Human prostate cancer cells (MDA PCa 2b) or vehicle were
injected into the right or left femur of SCID mice (n = 8). Radiography, computed
tomography, and magnetic resonance imaging were performed 5 and 8 weeks later (n
= 7). Bone scintigraphy (n = 6) was also performed at week 8. Imaging findings
were compared with histology and correlated with contemporaneous serum prostate
specific antigen levels. RESULTS: Among the modalities evaluated, only MR imaging
delineated prostate tumors involving bone. Tumor volume assessed by MR imaging
correlated with PSA levels (R(2) = 0.87, P < 0.001). MR imaging of tumors
corresponded with histology. Imaging of mineralized bone by CT corresponded with
histology. CONCLUSION: In a mouse model, prostate tumors involving bone can be
quantified using MR imaging.
PMID- 17031814
TI - Effects of obesity and height on prostate-specific antigen (PSA) and percentage
of free PSA levels among African-American and Caucasian men.
AB - BACKGROUND: Prior studies suggest that obese men have lower prostate-specific
antigen (PSA) levels than leaner men. Caucasian (CA) men also may have lower PSA
levels than African-American (AA) men, but the relevance of body size to racial
disparities in PSA levels is unclear. The association between body mass index
(BMI) and height on PSA and percentage of free PSA (%fPSA) was investigated
within AA and CA men without a prior prostate cancer diagnosis. METHODS: AA (n =
150) and CA (n = 149) men of similar socioeconomic status completed an extensive
in-person interview and donated blood. PSA and %fPSA levels were compared across
race, BMI, and height categories after adjusting for age and other factors.
RESULTS: PSA levels decreased with increasing BMI (PSA = .72, .69, .67, .59 ng/mL
for BMI 18.5 to <25, 25 to <30, 30 to <35, and > or =35, respectively; P(trend) =
.18), and trends were significant among men less than age 60 years (PSA = .81,
.76, .66, .59, respectively; P(trend) = .02). fPSA also significantly decreased
with BMI among men <60 years (P(trend) = .04). In contrast, %fPSA was not
associated with BMI. However, %fPSA increased 27% across height categories
(P(trend) = .02). PSA levels were significantly lower among CA men (PSA(AA) =
0.87, PSA(CA) = 0.63 ng/mL; P < .01), whereas %fPSA levels did not differ by
race. Also, associations between body size and PSA or %fPSA did not significantly
differ by race, and adjustment for BMI and height had no effect on the racial
disparity in PSA (PSA(AA) = 0.87, PSA(CA) = 0.63 ng/mL; P < .01). CONCLUSIONS:
The data suggest that race, BMI, and height are independently associated with PSA
and %fPSA levels.
PMID- 17031816
TI - Whole-body magnetization transfer contrast imaging.
AB - PURPOSE: To demonstrate the feasibility of whole-body magnetization transfer (MT)
contrast imaging. MATERIALS AND METHODS: Whole-body MT imaging was performed on
eight healthy volunteers and five patients (mean age=40.5+/-17.8 years) with
diagnoses of dermatomyositis (N=1), B-symptoms with suspicion of paraneoplastic
disease (N=1), metastatic malignant melanoma (N=1), and multiple sclerosis (MS)
(N=2). Measurements were carried out on a 1.5-Tesla whole-body MR scanner capable
of parallel signal reception. A three-dimensional (3D) gradient-echo sequence
(TR=17 msec, TE=4.8 msec, flip angle=10 degrees) was applied in combination with
a Gaussian off-resonance MT preparation pulse acting at an off-resonance of 1.500
Hz with a 500 degrees effective flip angle. Whole-body images were constructed
from five different body regions. RESULTS: In all subjects, whole-body MT
contrast images were obtained within less than 20 minutes of measuring time. The
images showed sufficient diagnostic image quality to assess the patients'
pathologies. The MT ratios (MTRs, in percent units) for the volunteers were as
follows: white matter (WM) 51.1+/-1.0, gray matter (GM) 42.2+/-1.3, skeletal
muscle (mean value of four muscle groups) 50.3+/-2.1, liver 39.4+/-3.2, spleen
31.8+/-2.6, renal cortex 30.4+/-1.9, and renal medulla 25.6+/-1.3. The MTRs for
the pathologies were as follows: skeletal muscle in dermatomyositis approximately
30, metastases in malignant melanoma 30.7-36.0, uterus myoma 49.3, and MS lesions
30-40. CONCLUSION: Our preliminary data indicate that MT contrast in whole-body
MRI is feasible, and may be useful for rapid whole-body assessment of diseases
that exhibit high contrast in MT imaging, such as MS and muscular disorders.
PMID- 17031815
TI - Genome-wide linkage of 77 families from the African American Hereditary Prostate
Cancer study (AAHPC).
AB - BACKGROUND: The African American Hereditary Prostate Cancer (AAHPC) Study was
designed to recruit families with early-onset disease fulfilling criteria of
>or=4 affected. METHODS: We present a approximately 10 cM genome-wide linkage
(GWL) analysis on 77 families including 254 affected and 274 unaffected
genotyped. RESULTS: Linkage analysis revealed three chromosomal regions with
GENEHUNTER multipoint HLOD scores >or=1.3 for all 77 families at 11q22, 17p11,
and Xq21. One family yielded genome-wide significant evidence of linkage (LOD =
3.5) to the 17p11 region with seven other families >or=2.3 in this region. Twenty
nine families with no-male-to-male (MM) transmission gave a peak HLOD of 1.62
(alpha = 0.33) at the Xq21 locus. Two novel peaks >or=0.91 for the 16 families
with '>6 affected' occurred at 2p21 and 22q12. CONCLUSIONS: These chromosomal
regions in the genome warrant further follow-up based on the hypothesis of
multiple susceptibility genes with modest effects, or several major genes
segregating in small subsets of families.
PMID- 17031817
TI - Detection of hepatic metastases using ferucarbotran-enhanced MR imaging:
feasibility and diagnostic accuracy of three-dimensional sensitivity-encoding
water-excitation multishot echo-planar sequence (3D-SWEEP).
AB - PURPOSE: To evaluate the diagnostic accuracy of a ferucarbotran-enhanced three
dimensional sensitivity-encoding water-excitation multishot echo-planar sequence
(3D-SWEEP) for detecting hepatic metastases compared to a T2*-weighted fast field
echo (FFE) sequence. MATERIALS AND METHODS: Twenty-five consecutive patients with
hepatic metastases underwent ferucarbotran-enhanced MRI on a 1.5-T unit before
hepatic resections. Eighty-two foci of metastases were confirmed by
histopathology or intraoperative ultrasonography (US). Signal-intensity decay
(SID), tumor-to-liver contrast (TLC), and image quality were compared between T2*
weighted FFE and 3D-SWEEP. Three independent observers reviewed three imaging
sets: set 1, without 3D-SWEEP or T2*-weighted FFE; set 2, with T2*-weighted FFE;
and set 3, with 3D-SWEEP. The mean values of areas under alternative free
response receiver operating characteristic curves (Az) and sensitivities were
compared among the three sets. RESULTS: SID and TLC were significantly greater
for 3D-SWEEP than T2*-weighted FFE, although 3D-SWEEP had poorer image quality.
The mean Az and sensitivity were significantly greater for set 3 compared to set
1 for detecting overall lesions, and compared to sets 1 and 2 for detecting
lesions of 1-2 cm in diameter. CONCLUSION: Despite relatively prominent
artifacts, ferucarbotran-enhanced 3D-SWEEP was more sensitive and accurate than
T2*-weighted FFE for detecting hepatic metastases.
PMID- 17031818
TI - Model-based registration for dynamic cardiac perfusion MRI.
AB - PURPOSE: To assess the accuracy of a model-based approach for registration of
myocardial dynamic contrast-enhanced (DCE)-MRI corrupted by respiratory motion.
MATERIALS AND METHODS: Ten patients were scanned for myocardial perfusion on 3T
or 1.5T scanners, and short- and long-axis slices were acquired. Interframe
registration was done using an iterative model-based method in conjunction with a
mean square difference metric. The method was tested by comparing the absolute
motion before and after registration, as determined from manually registered
images. Regional flow indices of myocardium calculated from the manually
registered data were compared with those obtained with the model-based
registration technique. RESULTS: The mean absolute motion of the heart for the
short-axis data sets over all the time frames decreased from 5.3+/-5.2 mm (3.3+/
3.1 pixels) to 0.8+/-1.3 mm (0.5+/-0.7 pixels) in the vertical direction, and
from 3.0+/-3.7 mm (1.7+/-2.1 pixels) to 0.9+/-1.2 mm (0.5+/-0.7 pixels) in the
horizontal direction. A mean absolute improvement of 77% over all the data sets
was observed in the estimation of the regional perfusion flow indices of the
tissue as compared to those obtained from manual registration. Similar results
were obtained with two-chamber-view long-axis data sets. CONCLUSION: The model
based registration method for DCE cardiac data is comparable to manual
registration and offers a unique registration method that reduces errors in the
quantification of myocardial perfusion parameters as compared to those obtained
from manual registration.
PMID- 17031819
TI - Processing, properties, and in vitro bioactivity of polysulfone-bioactive glass
composites.
AB - The mismatch between the mechanical properties of bioceramics and natural tissue
has restricted in several cases a wider application of ceramics in medical and
dental fields. To overcome this problem, polymer matrix composites can be
designed to combine bioactive properties of some bioceramics with the superior
mechanical properties of some engineering plastics. In this work, polymer
particulate composites composed of a high mechanical-property polymer and
bioactive glass particles were produced and both the in vitro bioactivity and
properties of the system were investigated. Composites with different volume
fraction and particle size were prepared. In vitro tests showed that hydroxy
carbonate-apatite can be deposited on the surface of a composite as early as 20 h
in a simulated body fluid. Ionic evolution from a composite with 40% volume
fraction of particles was demonstrated to be similar to bulk bioactive glasses.
The mechanical properties of some of the obtained composites had values
comparable with the ones reported for bone. Moreover, a physical model based on
dynamical mechanical tests showed evidences that the interface of the composite
was aiding in the stress transfer process.
PMID- 17031820
TI - Increased osteoblast adhesion on nanograined Ti modified with KRSR.
AB - Peptide sequences such as lysine-arginine-serine-arginine (KRSR) selectively bind
transmembrane proteoglycans (e.g. heparin sulfate) of osteoblasts (bone-forming
cells) and are, therefore, actively being investigated for orthopedic
applications. Further, nanophase materials (or materials with grain or particle
sizes less than 100 nm) are promising new materials that promote new bone growth
more than compared to conventional (that is, micron grain or particle size)
materials. To combine the above two promising approaches for improving orthopedic
implants, the objective of this in vitro study was to functionalize titanium (Ti)
surfaces (both nanophase and conventional) with KRSR peptides and study their
osteoblast cell adhesive properties. Materials were characterized by X-ray
photoelectron spectroscopy, scanning electron microscopy, and atomic force
microscopy. Results of this in vitro study provided evidence of increased
osteoblast adhesion on nanophase compared to conventional Ti whether
functionalized with KRSR or not. Results further showed that the immobilization
of KRSR onto Ti (both nanophase and conventional) increased osteoblast adhesion
compared to respective nonfunctionalized Ti and those functionalized with the
negative control peptide KSRR. Most importantly, osteoblast adhesion on
nonfunctionalized nanophase Ti increased compared to conventional Ti
functionalized with KRSR. Further, select initial osteoblast adhesion was
observed to occur at particle boundaries for any type of nanophase and
conventional Ti formulated in this study. In summary, results provided evidence
that not only should nonfunctionalized nanophase Ti be further studied for
improved orthopedic applications but so should nanophase Ti functionalized with
KRSR.
PMID- 17031821
TI - Enhancement of in vitro osteogenesis on titanium by chemically produced
nanotopography.
AB - The surface characteristics of biomaterials can influence protein adsorption,
cellular functions, and ultimately tissue formation. Controlled chemical
oxidation of titanium-based surfaces with a mixture of H(2)SO(4)/H(2)O(2) creates
a nanopatterned surface that has been shown to affect early osteogenic events.
The objective of this study was to evaluate the effect over time of this
nanopattern on various key parameters of osteogenesis, and determine whether
these effects ultimately translate into more mineralized matrix production.
Osteogenic cells were obtained by enzymatic digestion of newborn rat calvaria and
grown on treated and untreated titanium discs for periods of up to 14 days.
Alkaline phosphatase activity peaked earlier and cell number was higher as of day
7 on the nanopatterned discs. Immunofluorescence showed that the treated surface
favored early bone sialoprotein and osteopontin secretion, and fibronectin
accumulation. Alizarin red staining revealed that, at days 10 and 14, there were
significantly more mineralized nodules on treated than on untreated discs. These
results demonstrate that simple chemical treatment of titanium with
H(2)SO(4)/H(2)O(2) accelerates the in vitro osteogenic potential of calvaria
derived cells. They also suggest that this treatment may represent an
advantageous approach for producing "intelligent surfaces" that stimulate bone
formation and enhance bone-implant contact.
PMID- 17031822
TI - Antibacterial nanosized silver substituted hydroxyapatite: synthesis and
characterization.
AB - The silver (0.5-3 at %) substituted nanosize hydroxyapatites (AgHAs) were
synthesized by microwave processing. The X-ray diffraction (XRD) peaks are very
broad, indicating that the AgHAs were of nanosize (30 nm). Transmission electron
microscopy analysis shows needle-like morphology of AgHA, having length 60-70 nm
and width 15-20 nm. The AgHA phase was stable up to 700 degrees C without any
secondary phases. The antibacterial effect of AgHA against Escherichia coli and
Staphylococcus aureus was observed by spread plate method, even for low
concentration of silver ions (0.5%) with 1 x 10(5) cells/mL of respective
bacterial culture, after a 48 h incubation period. However, some colonies of E.
coli were seen with a high dose of 1 x 10(8) cells/mL after 24 h. The zone of
inhibition by disc diffusion test method was found to vary with the amount of
silver in the sintered AgHA pellets, for both the bacteria, after 24 h of
inoculation. Osteoblast cell attachment in varying density was noticed on AgHA
samples with 0.5, 1.0, and 1.5% silver substitution. However, osteoblast
spreading was significantly greater on 0.5% AgHA compared to 1.0 or 1.5%
substituted AgHA samples. Thus, the low amount of AgHA has a potential of
minimizing the risk of bacterial contamination, without compromising the
bioactivity, and is expected to display greater biological efficacy in terms of
osseointegration.
PMID- 17031823
TI - Effect of the solution flow rate on the in vitro bioactivity of 2.5CaO x 2SiO(2)
glass.
AB - A comparative study of in vitro bioactivity of 2.5CaO x 2SiO(2) glass has been
carried out by soaking it in a simulated body fluid, with continuously and
periodic exchange of this solution (dynamic and differential protocols). Dynamic
assays were carried out at different solution flow rates, 3 mL/h, 6 mL/h, 12
mL/h, to study the influence of flow rate on glass reactivity. Glass surface was
studied by Fourier transform infrared spectroscopy, scanning electron microscopy,
and energy dispersive spectroscopy so as to compare the behavior in the two
procedures, revealing that in both cases an apatite layer is formed on the glass
surface, although there are differences on deposition rate and morphology, which
are also influenced by the solution flow rate.
PMID- 17031824
TI - Macrophage behavior on multilayered DNA-coatings in vitro.
AB - A pivotal factor to consider in the development of biomaterials and biomaterial
coatings is the inflammatory response to these materials. The insertion of
implants is followed by protein adsorption and subsequent interactions with
cellular components of the biological surroundings, in which macrophages play a
dominant role through the production of a myriad of signaling molecules. In view
of this, the aims of the present study were to evaluate (i) gross protein
adsorption to, and (ii) in vitro behavior of macrophages on novel biomaterial
coatings, composed of poly-D-lysine (PDL) or poly(allylamine hydrochloride) (PAH)
and DNA, and to compare these coatings with negative (noncoated glass) and
positive controls (noncoated glass + LPS-stimulation). The results demonstrate
that multilayered DNA-coatings do not affect gross protein adsorption compared to
noncoated controls. Cell culture experiments showed that the attachment to, and
viability and morphology of two types of macrophages cultured on multilayered DNA
coatings is comparable to noncoated controls. Still, macrophages repeatedly
showed decreased secretion levels of the proinflammatory cytokine TNF-alpha on
multilayered DNA-coatings, whereas no differences were observed in the secretion
of IL-1beta, IL-10, and TGF-beta1. Appropriate animal studies are required to
elucidate if these in vitro indications have clinical effects on the inflammatory
and wound healing processes around implants.
PMID- 17031825
TI - Detection of HCV antigens in liver graft: relevance to the management of
recurrent post-liver transplant hepatitis C.
AB - The aim of this study was to evaluate how the immunohistochemical detection of
liver hepatitis C virus (HCV) antigens (HCV-Ag) could support the histologic
diagnosis and influence the clinical management of post-liver transplantation
(LT) liver disease. A total of 215 liver specimens from 152 HCV-positive patients
with post-LT liver disease were studied. Histologic coding was: hepatitis (126),
rejection (34), undefined (24; coexisting rejection grade I and hepatitis), or
other (31). The percentage of HCV-Ag infected hepatocytes were evaluated, on
frozen sections, by an immunoperoxidase technique. HCV-Ag were detectable early
in 57% of cases within 30 days post-LT, 92% of cases between 31 and 180 days, and
74% of cases after more than 180 days. Overall, HCV-Ag were detected more
frequently in histologic hepatitis as compared to rejection (P < 0.0001) with a
higher percentage of positive hepatocytes (P < 0.00001). In 16 patients with a
high number of HCV-Ag-positive hepatocytes (65%; range 40-90%) a clinical
diagnosis of recurrent hepatitis (RHC) was made despite inconclusive
histopathologic diagnosis. Multivariate analysis identified the percentage of HCV
Ag-positive hepatocytes and the time post-LT as independent predictors for RHC (P
= 0.008 and P = 0.041, respectively) and the number of HCV-Ag-positive
hepatocytes >/=50% as the only independent predictor for nonresponse (P < 0.001)
in 26 patients treated with alpha-interferon plus ribavirin. In conclusion, HCV
reinfection occurs early post-LT, reaching its peak within 6 months.
Immunohistochemical detection of post-LT HCV reinfection support the diagnosis of
hepatitis when the histologic features are not conclusive. A high number of
infected cells, independently from the genotype, represents a negative predictive
factor of response to antiviral treatment.
PMID- 17031826
TI - Recurrence of autoimmune liver disease after liver transplantation: a systematic
review.
AB - Recurrence of autoimmune liver disease in allografts has long been a topic of
debate. We conducted a systematic review of the literature to examine the
reported incidence of recurrence after liver transplantation of primary biliary
cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis
(AIH). The MEDLINE, EMBASE, and Cochrane electronic databases were used to
identify articles. The inclusion criteria used were articles on patients with at
least 90 days of posttransplantation follow-up, histologic criteria for diagnosis
of PBC and AIH recurrence, radiologic or histologic criteria or both for
diagnosis of PSC recurrence, and exclusion of other causes of liver disease
causing similar histologic findings. Incidence in individual studies was combined
to calculate the overall recurrence. Risk factors were analyzed whenever crude
data were available. Funnel plots were used to assess publication bias. Out of 90
articles identified, 43 met criteria for systematic review (PBC, 16; PSC, 14;
AIH, 13). The calculated weighted recurrence rate was 18% for PBC, 11% for PSC,
and 22% for AIH. No difference was found in PBC and AIH recurrence by type of
primary immunosuppression. There were not enough data to assess this issue in PSC
studies. There was evidence of publication bias among PSC and AIH studies but not
among PBC studies. In conclusion, recurrence of autoimmune liver disease after
liver transplantation appears to be a real concern. As these patients are
followed long-term, recurrence of disease may become the primary cause of
morbidity.
PMID- 17031827
TI - Transhepatic lactate gradient in relation to liver ischemia/reperfusion injury
during major hepatectomies.
AB - Hepatectomies performed under selective hepatic vascular exclusion are associated
with a series of events culminating in ischemia/reperfusion injury, a state that
shares common characteristics with situations known to result in global or
regional hyperlactatemia. Accordingly, we sought to determine whether lactate is
released by the liver during hepatic resections performed under blood flow
deprivation and what relation this has to a possible systemic hyperlactatemic
state. After ethical approval, 14 consecutive patients with resectable liver
tumors subjected to hepatectomy under inflow and outflow occlusion of the liver
were studied. Lactate concentrations were assessed in simultaneously drawn
arterial, portal venous, and hepatic venous blood before liver dissection and 50
minutes postreperfusion. Moreover, the transhepatic lactate gradient (hepatic
vein - portal vein) was calculated to see if there was net production or
consumption of lactate. Before hepatic dissection, the transhepatic lactate
gradient was negative, suggesting consumption by the liver. Fifty minutes after
reperfusion, this gradient became significantly positive, demonstrating release
of lactate by the liver (0.12 +/- 0.31 vs. -0.38 +/- 0.30 mmol/L, P < 0.05). The
magnitude of lactate release correlated with systemic arterial lactate levels at
the same time point (r(2) = 0.63, P < 0.001). A weaker but significant
correlation was demonstrated between the transhepatic lactate gradient
postreperfusion and systemic arterial lactate levels 24 hours postoperatively
(r(2) = 0.41, P = 0.013). A strong correlation between the transhepatic lactate
gradient postreperfusion and peak postoperative aspartate aminotransferase values
was also demonstrated (r(2) = 0.73, P < 0.001). The liver becomes a net producer
of lactate in hepatectomies performed under blood flow deprivation. This lactate
release can explain some of the systemic hyperlactatemia seen in this context and
relates to the extent of ischemia/reperfusion injury.
PMID- 17031828
TI - Impact of adult-to-adult living donor liver transplantation on access to
transplantation and patients' survival: an 8-year single-center experience.
AB - While the number of candidates for liver transplantation has increased in the
recent years, the pool of cadaveric donor organs has remained constant and the
waiting time progressively increases. These facts led us to start a program of
adult-to-adult living-donor liver transplantation in 1998. The aim of this study
was to compare the outcome of all patients put on the waiting list since 1998.
Between January 1, 1998, and January 1, 2005, 505 patients were put on the
waiting list in our center, and living donor liver transplantation was considered
in 57 cases (11.3%). At the time of evaluation (April 1, 2006), liver
transplantation was performed in 377 patients (46 living donor liver
transplantations), and 89 patients died on waiting list. On an intention-to-treat
basis, the 1-year survival rate from the time of listing was 87.5% in the "living
donor" group vs. 76.2% in the "cadaveric donor" group (P < 0.05), whereas the 1
year survival after liver transplantation was similar (92.3% vs. 86.9%). Our
living donor liver transplantation program was able to improve the access to
liver transplantation by reducing waiting time and the number of deaths on
waiting list, despite the fact that these patients were more critically ill
(liver failure and/or liver cancer).
PMID- 17031829
TI - Low viscosity histidine-tryptophan-ketoglutarate graft flush improves subsequent
extended cold storage in University of Wisconsin solution in an extracorporeal
rat liver perfusion and rat liver transplantation model.
AB - Adequate flushing for liver donation requires large fluid volumes delivered at a
high flow. This can be achieved more effectively with crystalloid solutions than
with colloid-based solutions. This study examined the combination of initial
histidine-tryptophan-ketoglutarate solution (HTK) graft flush and subsequent
storage in University of Wisconsin solution (UW) to that of the single use of
each solution. Livers from inbred Wistar rats were procured using aortic
perfusion with UW or HTK for initial perfusion and reflushed after 30 minutes
using either solution. In a third group, after perfusion with HTK, organs were
reflushed with UW. A 60-minute in-vitro recirculating perfusion was performed
after 24 hours of cold storage in the subsequent solution, as well as
allotransplantation after 18 and 24 hours of cold storage. In extracorporeal
perfusion, the HTK flush followed by UW storage was superior compared to the
single use of either UW or HTK solution, as measured by portal venous pressure,
bile flow, liver enzymes released into the effluent perfusate, glycerol leakage,
and histological examinations. These data were consistent with the
transplantation study. Histological damage and enzyme release after 5-day
survival were lowest in the HTK flush and subsequent UW storage groups following
18 hours of cold storage; likewise, the 5-day survival was superior following 24
hours of cold storage. In conclusion, the combined use of HTK solution for
initial graft rinse and subsequent storage in UW solution resulted in a
cumulative protection. Choosing low-viscosity HTK solution for the initial organ
flush may represent a feasible improvement in liver preservation, which also
further reduces the required amount of UW solution.
PMID- 17031830
TI - Identification of hepatitis B virus-specific lymphocytes in human liver grafts
from HBV-immune donors.
AB - Both animal and human studies have demonstrated the adoptive transfer of immunity
against hepatitis B virus (HBV) through liver transplantation that may be
attributed to the presence of HBV-specific immunocompetent cells of donor origin
in liver grafts. In this study, we characterized the resident lymphocytes in 41
human liver grafts by immunohistochemical staining and flow cytometry and
directly identified the intragraft HBV-specific lymphocytes in relation to the
donor's and subsequent recipient's immunity using enzyme-linked immunospot assay.
A significant number of HBV-specific T and B cells were detectable in 59.4%
(19/32) and 28.1% (9/32), respectively, of liver grafts from HBV-immune donors.
The presence of various HBV-specific lymphocytes was closely associated with each
other and with a higher serum titer of antibody against hepatitis B surface
antigen (anti-HBs) in donors (P < 0.05). After liver transplantation, 17 of 35
(48.6%) patients with chronic HBV infection showed a spontaneous anti-HBs
production, which was significantly associated with a higher number of donor
derived T lymphocytes specific for hepatitis B surface antigen (P = 0.043). In
conclusion, the presence of considerable numbers of donor-derived HBV-specific
immunocompetent cells in grafts may account for the adoptive transfer of HBV
immunity through liver transplantation.
PMID- 17031831
TI - Estimation of glomerular filtration rates after orthotopic liver transplantation:
Evaluation of cystatin C-based equations.
AB - Early detection of renal dysfunction in patients after orthotopic liver
transplantation is important. Creatinine-based equations to estimate glomerular
filtration rate (GFR) were found to be less accurate in liver transplant
recipients than in their original populations. Since cystatin C (CysC) is
independent from muscle mass and hepatic biosynthesis, we evaluated the
diagnostic accuracy of 3 CysC-based equations (Larson, Hoek, and Filler formulae)
that are based on the same CysC method as that of our center in comparison to the
abbreviated creatinine-based modification of diet in renal disease (MDRD) formula
in 59 liver transplant recipients. "True GFR" was measured by 99mTc-diethylene
triamine pentaacetic acid ((99m)Tc-DTPA) clearance. Neither correlation with the
GFR (correlation coefficients: 0.594-0.640) nor precision (root mean square
error: 15.7-18.17 mL/min/1.73 m(2)) differed significantly between the tested
formulae. The biases of the Hoek and Larsson formulae were significantly smaller
than those of the MDRD and Filler equations (-0.1 and -2.3 vs. 10.1 and 7.9
mL/min/1.73 m(2), respectively; P = 0.0023). Mean estimates of MDRD (61.9 +/-
21.4 mL/min/1.73 m(2)) and Filler (61.2 +/- 22.1 mL/min/1.73 m(2)) differed
significantly from the measured GFR (52.3 +/- 17.5 mL/min/1.73 m(2); P < 0.005),
whereas Larsson and Hoek did not (49.5 +/- 20.2 and 51.4 +/- 17.9 mL/min/1.73
m(2), respectively). Accuracy within 30% and 50% of the true GFR was best for the
Hoek (76.3% and 93.2%) formula, albeit not significantly different from MDRD
(64.4% and 83.1%). Taken together, these data show the best overall performance
for GFR estimates derived from the Hoek equation with respect to bias, precision,
and accuracy.
PMID- 17031832
TI - Correlation between dynamic susceptibility contrast perfusion MRI and methionine
metabolism in brain gliomas: preliminary results.
AB - PURPOSE: To evaluate in brain gliomas the relationship between tumor vascularity
measured by MR-based maximum regional cerebral blood volume (rCBV) and tumor
amino-acid metabolism based on maximum carbon-11 methionine (MET) uptake on
positron emission tomography (PET). MATERIALS AND METHODS: Eighteen patients with
histologically proven primary brain gliomas were included in the study. In
addition to conventional MR sequences, dynamic MR images, including a first-pass
gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence and a PET
study using MET, were acquired. Eleven patients had low-grade gliomas, and seven
had high-grade gliomas. rCBV ratios and MET uptake ratios normalized to the
contralateral white matter (WM) corresponding values were measured in each tumor.
Both maximum rCBV ratios and maximum MET uptake ratios were correlated to
histopathology. The maximum rCBV ratios were correlated to the maximum MET uptake
ratios. RESULTS: Both the maximum rCBV ratios and maximum MET uptake ratios of
high-grade gliomas were significantly higher than those of low-grade gliomas
(P<0.05). There was a significant positive correlation between maximum rCBV
ratios and maximum MET uptake ratios (Spearman: r=0.89, P<0.00001). CONCLUSION:
The maximum rCBV ratio and maximum MET uptake ratio are significantly correlated
in gliomas, reflecting a close link between amino acid uptake and vascularity in
these tumors.
PMID- 17031833
TI - Fast magnetization-driven preparation for imaging of contrast-enhanced coronary
arteries during intra-arterial injection of contrast agent.
AB - PURPOSE: To implement a short-duration magnetization preparation sequence, which
consists of a saturation followed by multiple inversion pulses, for imaging of
short-T1 species and suppression of long-T1 species. MATERIALS AND METHODS:
Computer optimizations were performed to derive preparation schemes that 1)
suppress long-T1 background species with T1>or=250 msec, 2) maximize the MZ of
contrast-enhanced (CE) structures with T1250 msec, and about a 30%
reduction for 20 msec10
mM in unbuffered solutions and > 50 mM in buffered solutions) may modify the
peptide structure and reduce its thermal stability, thereby interfering with
subsequent structural investigations of the peptide. Our results indicate that
HCl concentrations between 2 and 10 mM are adequate to remove essentially all TFA
impurities without any modification of the peptide secondary structure.
PMID- 17031870
TI - Studies on deprotection of cysteine and selenocysteine side-chain protecting
groups.
AB - We present here a simple method for deprotecting p-methoxybenzyl groups and
acetamidomethyl groups from the side-chains of cysteine and selenocysteine. This
method uses the highly elecrophilic, aromatic disulfides 2,2'-dithiobis(5
nitropyridine) (DTNP) and 2,2'-dithiodipyridine (DTP) dissolved in TFA to effect
removal of these heretofore difficult-to-remove protecting groups. The
dissolution of these reagents in TFA, in fact, serves to 'activate' them for the
deprotection reaction because protonation of the nitrogen atom of the pyridine
ring makes the disulfide bond more electrophilic. Thus, these reagents can be
added to any standard cleavage cocktail used in peptide synthesis.The p
methoxybenzyl group of selenocysteine is easily removed by DTNP. Only sub
stoichiometric amounts of DTNP are required to cause full removal of the p
methoxybenzyl group, with as little as 0.2 equivalents necessary to effect 70%
removal of the protecting group. In order to remove the p-methoxybenzyl group
from cysteine, 2 equivalents of DTNP and the addition of thioanisole was required
to effect removal. Thioanisole was absolutely required for the reaction in the
case of the sulfur-containing amino acids, while it was not required for
selenocysteine. The results were consistent with thioanisole acting as a
catalyst. The acetamidomethyl group of cysteine could also be removed using DTNP,
but required the addition of > 15 equivalents to be effective. DTP was less
robust as a deprotection reagent. We also demonstrate that this chemistry can be
used in a simultaneous cyclization/deprotection reaction between selenocysteine
and cysteine residues protected by p-methoxybenzyl groups to form a
selenylsulfide bond, demonstrating future high utility of the deprotection
method.
PMID- 17031871
TI - Bombesin analogs containing alpha-amino-isobutyric acid with potent anticancer
activity.
AB - Six octapeptide bombesin (BN) analogs were synthesized by substituting alpha
aminoisobutyric acid (Aib), in place of Ala9 or Gly11, or both, in the [D-Phe6,
desMet14]-BN (6-14) sequence: D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13-NH2
(P0). Additionally, Leu13 was replaced with isoleucine in two analogs and one of
the analogs was butanoylated at the N-terminus. The antiproliferative activity of
the analogs was tested in vitro on human pancreatic (MiaPaCa-2) and colon cancer
(SW620, HT29 and PTC) cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) assay. The analogs demonstrated anticancer
activity in the above cell lines at concentrations ranging from 0.01 nM to 1
microM. One of the analogs, P6, was evaluated for in vivo tumor regression in a
xenograft model of human primary colon cancer in athymic nude mice and was found
to cause significant reduction in tumor volume. NMR and molecular dynamics (MD)
simulation studies for this analog revealed the presence of a mixed 3(10)/alpha
helical structure. This study demonstrates that the designed BN analogs retain
their anticancer activity after the incorporation of the constrained amino acid,
Aib, and are potential molecules for future use in cancer therapy and drug
targeting.
PMID- 17031872
TI - Prenatal screening for congenital heart disease with four-chamber and outflow
tract views: a multicenter study.
AB - OBJECTIVE: Congenital heart diseases (CHD) are the most common congenital
anomalies, and most cases occur in the low-risk population. Prenatal ultrasound
screening based on visualization of the four-chamber view has had disappointing
results in detecting these anomalies thus far. The aim of this study was to
evaluate the diagnostic accuracy of ultrasound screening based on the combination
of the four-chamber and outflow-tract views. METHODS: We conducted a multicenter
prospective observational study in 15 obstetric units in the Piedmont Region,
Italy. All operators received specific training. Data were recorded regarding
visualization of the four-chamber view and the outflow tracts at each routine
scan in pregnancies without any risk factor. When an anomaly was suspected, the
patient was sent to the referral center. We obtained the follow-up data of the
newborns until discharge from hospital and calculated the diagnostic accuracy of
the test. RESULTS: 9074 ultrasound scans were performed on 7041 women and
complete follow-up information was available for 6368 of them. Fifty-eight cases
of CHD were observed at birth or postmortem (prevalence 9.1 per thousand); 38 of
them were diagnosed in utero. The sensitivity of the test was 65.5%, the
specificity 99.7%, the positive predictive value 70.4% and the negative
predictive value 99.7%. The sensitivity of the four-chamber view alone was 60.3%.
CONCLUSIONS: The sensitivity was significantly higher than that in a similar
study performed in 1997 in the same setting. This improvement can be attributed
in part to extension of the examination to the outflow-tract view, but also to
technological developments and better training of the operators.
PMID- 17031873
TI - Successful treatment of a recurrent Cesarean scar ectopic pregnancy by surgical
repair of the uterine defect.
PMID- 17031874
TI - Serum biochemistry correlates with the size of tubal ectopic pregnancy on
sonography.
AB - OBJECTIVE: To investigate whether there is a correlation between serum
biochemistry (human chorionic gonadotropin (hCG), CA 125, progesterone and
estradiol) and the common sonographic findings (blob sign, bagel sign or
extrauterine gestational sac with cardiac activity) or size of a tubal ectopic
pregnancy, and whether there is a difference in serum biochemistry between women
with a tubal ectopic pregnancy who are hemodynamically unstable (tachycardia,
hypotension, falling hemoglobin levels and/or acute severe abdominal pain) and
those who are hemodynamically stable. METHODS: This was a prospective cohort
study of 106 women with a tubal ectopic pregnancy. We noted transvaginal
ultrasound examination findings including adnexal mass size, and the serum levels
of hCG, CA 125, progesterone and estradiol. The data were analyzed
retrospectively. RESULTS: The mean maternal and gestational ages were 30.7+/-5.7
years and 44+/-4.2 days, respectively. There was no correlation between serum
markers and common sonographic findings. However, in the presence of the bagel
sign on ultrasound, hemodynamic stability was more common (P=0.03). The mean
serum hCG concentrations in tubal ectopic pregnancies<20 mm, 20-40 mm and >40 mm
in size were 2225.3+/-3166.9, 4124.8+/-6121.4, and 11 011.8+/-12 670.1 IU/mL,
respectively (P<0.001). Serum hCG, CA 125 and estradiol values were well
correlated with adnexal mass size; for CA 125 this correlation was linear. There
was no difference in serum biochemistry between hemodynamically stable and
hemodynamically unstable women. CONCLUSION: Common sonographic findings of tubal
ectopic pregnancy do not correlate with serum biochemistry. High levels of CA
125, hCG or estradiol may suggest a larger adnexal mass in women with
uncomplicated tubal pregnancies. Hemodynamically stable and hemodynamically
unstable women do not differ in their serum biochemistry.
PMID- 17031875
TI - Insect gonadotropic peptide hormones: some recent developments.
AB - Gonadotropic peptides are a new generation of peptide hormone regulators of
insect reproduction. They have been isolated from ovaries, oviducts, or brains of
insects. The subject of this paper is insect peptides that exert stimulatory or
inhibitory effects on ovarian development and oocyte maturation. On the basis of
the literature data and the results of our investigations, the structure and
biological properties of different groups of peptides are presented.
PMID- 17031879
TI - Lipidated ras and rab peptides and proteins--synthesis, structure, and function.
AB - Chemical biology can be defined as the study of biological phenomena from a
chemical approach. Based on the analysis of relevant biological phenomena and
their structural foundation, unsolved problems are identified and tackled through
a combination of chemistry and biology. Thus, new synthetic methods and
strategies are developed and employed for the construction of compounds that are
used to investigate biological procedures. Solid-phase synthesis has emerged as
the preferred method for the synthesis of lipidated peptides, which can be
chemoselectively ligated to proteins of the Ras superfamily. The generated
peptides and proteins have solved biological questions in the field of the Ras
superfamily GTPases that are not amendable to chemical or biological techniques
alone.
PMID- 17031881
TI - Aromaticity of tri- and tetranuclear metal-carbonyl clusters based on magnetic
criteria.
AB - Recently, the sigma-aromaticity model proposed for cyclopropane by Dewar was
employed to account for the stability of Group 8 trinuclear metal-carbonyl
compounds [M(3)(CO)(12)] (M=Fe, Ru, Os). This paper further examines this
hypothesis and provides the first quantitative evidence for the sigma
aromatic/antiaromatic nature of the [M(3)(CO)(12)]/[M(4)(CO)(16)] species based
on structural and nucleus-independent chemical-shift analysis. In addition, the
extent of electron delocalization in tetrahedral [M(4)(CO)(14)] and butterfly
[M(4)(CO)(15)] is analyzed and compared to prototype cycloalkanes. While
remarkable analogies exist between metal-carbonyls and cycloalkanes, transition
metals provide additional overlap possibilities that affect both the ring strain
and the magnetic properties of metal-carbonyl rings and cages.
PMID- 17031882
TI - Dihydroimidazophenanthridinium (DIP)-based DNA binding agents with tuneable
structures and biological activity.
AB - We have synthesised a library of dihydroimidazophenanthridinium cations (DIPs)
with large structural diversity (1-29) using a "one-pot" approach. The DNA
binding constants of DIPs range from 2x10(4) to 1.3x10(5) M(-1), and the free
energies for binding range from -5.9 to -6.40 kcal mol(-1). Viscosity
measurements demonstrated that the binding of the compounds caused DNA
lengthening, thus signifying binding by intercalation. The cytotoxicities of the
compounds were determined by tetrazolium dye-based microtitration assays and
showed a large range of values (0.09-11.7 microM). Preliminary molecular
modelling studies of the DNA-DIP interactions suggested that the DIP moieties can
interact with DNA by intercalation, and some R groups might facilitate binding by
minor-groove binding. The results provide insight into how to design biologically
active DNA binding agents that can interact in these ways.
PMID- 17031883
TI - Nitric oxide reductase: direct electrochemistry and electrocatalytic activity.
PMID- 17031884
TI - RNA-templated chemistry in cells: discrimination of Escherichia, Shigella and
Salmonella bacterial strains with a new two-color FRET strategy.
PMID- 17031885
TI - Ketoreduction in mycolactone biosynthesis: insight into substrate specificity and
stereocontrol from studies of discrete ketoreductase domains in vitro.
AB - Mycolactone, a polyketide toxin responsible for the extensive tissue destruction
seen in Buruli ulcer, is assembled on a modular polyketide synthase (PKS).
Despite operating on structurally different intermediates during synthesis, many
of the ketoreductase (KR) domains of the mycolactone (MLS) PKS have identical
sequences. This suggests that these enzymes might exhibit an unusually high level
of substrate promiscuity. However, we show here that when recombinant mycolactone
KR domains are tested with a range of surrogate substrates, their specificity
closely matches that of KR domains derived from other PKS systems. In addition,
our findings reinforce the role of substrate tethering for achieving
stereochemical control in modular PKSs by affecting the delicate energetics of
ketoreduction.
PMID- 17031886
TI - Identification of labile UDP-ketosugars in Helicobacter pylori, Campylobacter
jejuni and Pseudomonas aeruginosa: key metabolites used to make glycan virulence
factors.
PMID- 17031887
TI - Synthesis and characterization of oligodeoxynucleotides containing
naphthyridine:imidazopyridopyrimidine base pairs at their sticky ends.
Application as thermally stabilized decoy molecules.
AB - We describe the synthesis and properties of oligodeoxynucleotides (ODNs)
containing 1,8-naphthyridine C-nucleoside (Na-NO) and
imidazo[5',4':4,5]pyrido[2,3-d]pyrimidine nucleoside (Im-ON) at the termini. The
modified ODNs were more resistant (6 to 40 times) than natural DNA to snake venom
phosphodiesterase (SVPD). Although incorporation of one pair each of Na-NO:Im-ON
on the sticky ends of the duplex was insufficient for thermal stabilization (+2.5
degrees C per pair relative to the G:C pair), the duplex containing two
consecutive Na-NO:Im-ON pairs at its sticky ends was markedly stabilized
thermally. The stabilizing effect of the incorporation of additional Na-NO:Im-ON
pairs is estimated to be +7.8 degrees C per pair. Application as thermally
stabilized decoy molecules to NF-kappaB (p50) was also demonstrated. The DNA
duplexes containing the Na-NO:Im-ON pairs (ODN I:ODN II and ODN III:ODN IV) acted
as competitors to the natural NF-kappaB-binding duplex (ODN V: ODN VI), and the
calculated IC50 values of ODN I:ODN II and ODN III:ODN IV were 20.1+/-13.3 and
10.9+/-4.8 nM, respectively, greater than that of ODN V:ODN VI.
PMID- 17031888
TI - Selenolthiol and dithiol C-terminal tetrapeptide motifs for one-step purification
and labeling of recombinant proteins produced in E. coli.
AB - We have previously shown that a redox-active selenocysteine-containing
tetrapeptide-Sel-tag (Gly-Cys-Sec-Gly)-can be used as a C-terminal fusion motif
for recombinant proteins produced in Escherichia coli. This Sel-tag allows
selenolate-targeted one-step purification, as well as fluorescent labeling or
radiolabeling either with gamma emitters (75Se) or with positron-emitting
radionuclides (11C). Here we have analyzed four different redox-active C-terminal
motifs, carrying either dithiol (Gly-Cys-Cys-Gly or Ser-Cys-Cys-Ser) or
selenolthiol (Gly-Cys-Sec-Gly or Ser-Cys-Sec-Ser) motifs. Utilizing these
different functional motifs with the same recombinant protein (Fel d 1), we were
able to assess their relative reactivities and potential usefulness for
biotechnological applications. We found that all four redox-active tags could be
utilized for efficient one-step purification to provide pure protein from a crude
bacterial lysate through reversible binding to phenylarsine oxide sepharose, with
yields and purities comparable to those obtained for a His-tagged protein
purified by the more common approach with use of a Ni2+ column. For labeling with
electrophilic fluorescent or radioactive compounds, however, the selenolthiol
motifs were considerably more efficient than their dithiol counterparts. The
results thus show that both the selenolthiol- and the dithiol-containing tags can
serve as efficient alternatives to His-tags for protein purification, while the
selenolthiol motifs offer additional and unique potential for Sec-targeted
labeling. It should therefore be possible to utilize these multifunctional
tetrapeptide motifs to develop a wide range of novel biotechnological
applications based on Sec targeting with electrophilic compounds.
PMID- 17031889
TI - Three-step synthesis of sialic acids and derivatives.
PMID- 17031890
TI - Spontaneous knotting-from oligoamide threads to trefoil knots.
PMID- 17031891
TI - DNA logic gates based on structural polymorphism of telomere DNA molecules
responding to chemical input signals.
PMID- 17031892
TI - Mechanically induced generation of counterions inside surface-grafted charged
macromolecular films: towards enhanced mechanotransduction in artificial systems.
PMID- 17031893
TI - Click assembly of 1,2,3-triazole-linked dendrimers, including ferrocenyl
dendrimers, which sense both oxo anions and metal cations.
PMID- 17031894
TI - Control of vesicular morphologies through hydrophobic block length.
PMID- 17031895
TI - Selective binding and easy separation of C70 by nanoscale self-assembled
capsules.
PMID- 17031896
TI - Nanostructured thermosensitive polymers with radical scavenging ability.
AB - The thermosensitive [60]fullerene end-capped poly(N-isopropylacrylamide) was
successfully synthesized by the reaction of C(60) with dithiobenzoate-terminated
poly(N-isopropylacrylamide), which was prepared by reversible addition
fragmentation chain-transfer (RAFT) polymerization in the presence of
azobisisobutyronitrile (AIBN). Its structure was determined by FTIR, UV/Vis, and
carbon and proton NMR spectroscopy as well as by size exclusion chromatography
(SEC). The novel fullerenated polymer retained the thermosensitivity of poly(N
isopropylacrylamide). Moreover, it is soluble in water and most of the common
organic solvents. Interestingly, it was able to form nanoparticle clusters in
methanol and exhibited significant radical scavenging ability in cell viability
and metabolic activity tests with fibroblasts and NOR-3 radicals.
PMID- 17031897
TI - A distance geometry heuristic for expanding the range of geometries sampled
during conformational search.
AB - A recent study of crystal structures of protein-ligand complexes has shown that
bioactive conformations tend to be more extended than random ones (Diller and
Merz, J. Comput. Aid. Mol. Des. 2002, 16, 105-112). Existing conformational
sampling techniques produce molecular conformations with a distribution of
geometric sizes that may not cover that of the bioactive conformations. Here, we
describe a simple heuristic for biasing the conformational search toward more
extended or compact conformations, while maintaining excellent sampling. The
method uses a boosting strategy to generate a series of conformations, each of
which is at least as extended (or compact) as the previous one. We demonstrate
that this method significantly expands the range of geometric sizes generated
during the search and thus increases the efficiency of sampling bioactive
conformations.
PMID- 17031898
TI - Diatropicity of tetraazanaphthalenes.
AB - Tetraazanaphthalenes are diatropic molecules, whose magnetic response to a
magnetic field perpendicular to the molecular plane closely resembles that of
naphthalene. The out-of-plane component of the magnetic susceptibility tensor and
its strong anisotropy can be used as quantifiers of magnetic aromaticity. Maps
showing streamlines and modulus of the current density field provide clear
evidence for diatropicity of these systems. They also explain the strong
anisotropy of carbon and nitrogen magnetic shielding, which is determined by the
big out-of-plane component of the nuclear shielding tensor. The electronic ring
currents observed in the map deshield the nuclei of ring hydrogens by enforcing
the local magnetic field and diminishing the out-of-plane component of proton
shielding.
PMID- 17031899
TI - Accurate relativistic adapted Gaussian basis sets for Cesium through Radon
without variational prolapse and to be used with both uniform sphere and Gaussian
nucleus models.
AB - Accurate relativistic adapted Gaussian basis sets (RAGBSs) from Cs (Z = 55)
through Rn (Z = 86) without variational prolapse were developed by using the
polynomial version of the Generator Coordinate Dirac-Fock method. The RAGBSs
presented here can be used with any of two popular finite nucleus models, the
uniform sphere and the Gaussian models. The largest RAGBS error is 4.5 mHartree
for Radon with a size of 30s27p17d11f.
PMID- 17031900
TI - Safety concerns cast shadow over novel class of HIV drugs.
PMID- 17031901
TI - Informal consultation on preventing disability from lymphatic filariasis, WHO,
Geneva, August 2006.
PMID- 17031902
TI - Midwife seeks to work for RIPI.
PMID- 17031903
TI - Recruiting ideas.
PMID- 17031904
TI - Urine eosinophils method.
PMID- 17031905
TI - Scandinavian Cardiovascular Journal.
PMID- 17031906
TI - RTAs and horse ID under the spotlight at this year's BEVA congress.
PMID- 17031907
TI - Self-reported chronic conditions and EQ-5D index scores in the US adult
population.
AB - OBJECTIVE: To examine the unique health-related quality of life (HRQoL)
decrements associated with common chronic conditions in the general US adult
population. METHODS: Data were obtained from a study aimed at establishing a US
population-based set of preference weights for the health states defined by the
EQ-5D. The EQ-5D is a brief, self-completed instrument for describing and valuing
HRQoL. As part of that study, along with the EQ-5D items, data regarding socio
demographic characteristics and chronic medical conditions were collected. The EQ
5D has five dimensions, from which an index score can be calculated that falls on
a scale where 0.0 = death and 1.0 = perfect health. Ordinary least squares
regression models were conducted using the EQ-5D index score as the dependent
variable to estimate the association between each chronic condition and the index
score after adjusting for socio-demographic variables. The population sampling
weights were applied in the analyses to adjust for the over-sampling of the
minority groups. RESULTS: Approximately three-fifths (62.5%) of the study sample
reported having at least one of the 18 chronic medical conditions;
sinusitis(24.8%), hypertension (23.5%), and arthritis (21.5%) were the most
commonly reported conditions. The chronic conditions that had the greatest
negative association with EQ-5D index scores were depression and arthritis.
CONCLUSION: Unique associations were found between several chronic conditions and
HRQoL after accounting for the presence of other conditions and socio-demographic
characteristics. The results of this study provide an indication of the relative
HRQoL decrements associated with various chronic conditions in the general US
adult population. The major limitation of this analysis is the uncertainty of the
causal relationship between chronic conditions and HRQoL due to the cross
sectional nature of the study data. In addition, because it was unknown how well
the conditions were managed, caution is needed in interpreting study results
regarding the relative impact of chronic conditions on HRQoL.
PMID- 17031908
TI - Decisions and revisions.
PMID- 17031909
TI - Bioethics and health disparity: Adding diversity to the debate.
AB - BACKGROUND: Advances in biomedical science and technology have raised profound
challenges to the way we think, feel, and act regarding human practices and
ideals. Ethicists are needed from diverse populations who can enhance moral
debate by offering cultural insight as choices are made as to how society should
approach the expanding medical and biological possibilities. METHODS: In this
text, we review comments from bioethicists who are focusing on the moral issues
surrounding health disparity. RESULTS AND CONCLUSIONS: The purpose of the report
is to ask the reader to begin to understand how to be an informed partner in this
ethical debate.
PMID- 17031910
TI - Treatment of prehypertension: how soon is soon enough? What therapy should be
used?
PMID- 17031911
TI - [Diarrhea caused by antibiotics].
PMID- 17031912
TI - Surgical approaches for the management of idiopathic thoracic scoliosis and the
indications for combined anterior-posterior technique.
AB - The indications for surgical intervention in patients with idiopathic scoliosis
have been well defined. The goals of surgery are to achieve fusion and arrest
progressive curvature while restoring normal coronal and sagittal balance. As
first introduced by Harrington, posterior fusion, the gold standard of treatment,
has a proven record of success. More recently, anterior techniques for performing
fusion procedures via either a thoracotomy or a retroperitoneal approach have
been popularized in attempts to achieve better correction of curvature, preserve
motion segments, and avoid some of the complications of posterior fusion such as
the development of the flat-back syndrome. Anterior instrumentation alone,
although effective, can be kyphogenic and has been shown to be associated with
complications such as pseudarthrosis and instrumentation failure. Performing a
combined approach in patients with scoliosis and other deformities has become an
increasingly popular procedure to achieve superior correction of deformity and to
minimize later complications. Indications for a combined approach (usually
consisting of anterior release, arthrodesis with or without use of
instrumentation, and posterior segmental fusion) include: prevention of
crankshaft phenomenon in juvenile or skeletally immature adolescents; correction
of large curves (75 degrees ) or excessively rigid curves in skeletally mature or
immature patients; correction of curves with large sagittal-plane deformities
such as thoracic kyphosis (> 90 degrees ) or thoracic lordosis (> 20 degrees );
and correction of thoracolumbar curves that need to be fused to the sacrum.
Surgery may be performed either in a staged proceedure or, more commonly, in a
single sitting. The authors discuss techniques for combined surgery and
complication avoidance.
PMID- 17031913
TI - Coexistence of two different intraspinal tumors. Case report and review of the
literature.
AB - The occurrence of multiple neoplasms in the central nervous system is well
documented. In von Recklinghausen's disease, patients frequently present with
multiple neurofibromas and/or meningiomas at different sites within the spinal
axis. However, the presence of multiple, histologically different spinal tumors
in the absence of von Recklinghausen's disease is extremely rare. The authors
describe a patient with progressive paraparesis in whom an extradural, malignant
lesion and a separate benign, intradural tumor of the thoracic spine were found.
The histological diagnosis of the intradural tumor was a pigmented schwannoma. On
review of the literature, the authors found nine additional cases of coexisting,
histologically different tumors of the spine. The majority of these tumors
occurred in the thoracic spine and, not unexpectedly, intradural meningiomas and
schwannomas prevailed. Except for the presumed same mesenchymal cell origin of
neurinomas and meningiomas, no explanation for the coexisting, different spinal
tumors could be determined.
PMID- 17031914
TI - Anterior thoracic intradural arachnoid cysts. Case report and review of the
literature.
AB - Anterior thoracic intradural arachnoid cysts (ATIACs) are a rare cause of spinal
cord and nerve root compression, for which different treatment strategies have
been proposed. Although ATIAC represents a well-known clinical entity, the choice
of surgical method has not been uniform, and no study has been specifically
designed to compare the results of the different treatment options adopted. The
authors report the case of a 40-year old man with a 1-year history of dorsal
pain, weakness in the lower extremities, gait disturbance, and mild sexual and
urinary dysfunction. On neurological examination spastic paraparesis, lower
extremity hypertonia, and hypesthesia below T-2 were demonstrated. Magnetic
resonance imaging revealed the presence of an ATIAC at the T-2 level. The patient
underwent complete microsurgical removal of the cyst. The authors conducted a
Medline search of the relevant literature from 1966 to 1998 and also obtained
data on other cases in which patients underwent surgical treatment of ATIAC. The
literature search yielded five such cases. Treatment strategies were complete
excision and fenestration followed by placement of a shunt. In addition, one case
was characterized by intraoperative cyst rupture during retraction of the spinal
cord. Correct preoperative workup coupled with microneurosurgical technique allow
for successful removal of the lesion and excellent outcome. Based on the
literature review and the results in our case, the complete excision of ATIAC is
associated with an excellent outcome, which is different from results achieved
using other surgical strategies.
PMID- 17031915
TI - Functional neuronavigation with magnetoencephalography: outcome in 50 patients
with lesions around the motor cortex.
AB - The authors conducted a study to evaluate the clinical outcome in 50 patients
with lesions around the motor cortex who underwent surgery in which functional
neuronavigation was performed. The sensorimotor cortex was identified in all
patients with the use of magnetoencephalography (MEG). The MEG-source
localizations were superimposed onto a three-dimensional magnetic resonance
image, and the image data set was then implemented into a neuronavigation system.
Based on this setup, the surgeon chose the best surgical strategy. During
surgery, the pre- and postcentral gyrus were identified by neuronavigation, and
in addition, the central sulcus was localized using intraoperative recording of
somatosensory evoked potentials. In all cases MEG localizations of the sensory or
motor cortex were correct. In 30% of the patients preoperative paresis improved,
in 66% no additional deficits occurred, and in only 4% (two patients)
deterioration of neurological function occurred. In one of these patients the
deterioration was not related to the method. The method of incorporating
functional data into neuronavigation systems is a promising tool that can be used
in more radical surgery to cause less morbidity around eloquent brain areas.
PMID- 17031916
TI - Surgical treatment for acute spinal cord injury study pilot study #2: evaluation
of protocol for decompressive surgery within 8 hours of injury.
AB - Acute spinal cord injury (SCI) is a major public health problem for which there
is still only limited treatment available. The National Acute Spinal Cord Injury
Study-2 (NASCIS-2) and -3 clinical trials demonstrated that the use of acute
pharmacotherapy with methylprednisolone can attenuate the secondary injury
cascade if administered within 8 hours of acute SCI. However, no trial has been
performed to examine whether acute surgical decompressive procedures within this
critical 8-hour time window can improve patients' neurological outcome. The
purpose of the current prospective Surgical Treatment for Acute Spinal Cord
Injury Study (STASCIS) pilot study was to determine the feasibility of obtaining
a radiological diagnosis of spinal canal compromise of 25% or more and to perform
spinal cord (C3-T1) decompressive procedures by 8 hours postinjury. One of the
following three decompressive methods was used: 1) traction alone; 2) traction
and surgery; or 3) surgery alone. Twenty-six patients from eight North American
centers were entered into the study between 1996 and 1997. Significant
difficulties were encountered in many centers in performing immediate magnetic
resonance imaging examination in patients with acute SCI. Fewer than 10% of acute
cervical SCI patients could be enrolled into this protocol mainly because the
combination of the required time for rescue, resuscitation, transport, imaging
study, and surgical preparation exceeded the 8-hour injury-to-decompressive
surgery window. Eleven patients underwent decompressive procedures initially by
being placed in traction at a mean time of 10.9 hours postinjury. Those patients
not undergoing this procedure underwent decompressive surgery at a mean time of
40.1 hours. However, the surgical decompressive procedure was completed within 12
hours in seven patients. As a result of these findings, several major changes
have been made to the STASCIS protocol for early decompressive therapy.
PMID- 17031917
TI - The fate of the compressed deformed spinal cord after decompressive surgery: MR
imaging and histopathological findings in experimental studies.
AB - The authors conducted a study in which they applied the spinal cord compression
decompression model in rabbits to investigate the morphological changes and
histopathological findings in the deformed spinal cord over a long-term period
after performing decompressive surgery. Throughout the experimental period,
mangnetic resonance (MR) images were obtained frequently; after obtaining a final
MR image, the spinal cord was dissected and underwent histological examination.
Immediately after decompressive surgery, axial T1-wieighted MR imaging revealed
an increase in the cross-sectional area of the spinal cord during the 1st and 2nd
weeks. The spinal cord area achieved a peak at an average of 5.9 weeks after
decompressive surgery, when it displayed isointensity on T1- and high-intensity
on T2-weighted images. The main histological findings were spongy changes in the
white matter, which persisted for 4 months postsurgery. There was a significant
correlation between the presurgical spinal cord area and the postsurgical
decreased number of motor neuron cells. Based on the MR imaging and
histopathological studies, although the deformed spinal cord that underwent
compression for 3 months was immediately restored morphologically after
decompressive surgery, the change in quality in the spinal cord persisted at
least 4 months.
PMID- 17031918
TI - Review of clinical trials of neuroprotection in acute spinal cord injury.
AB - In this paper the authors review the clinical trials of neuroprotection that have
been performed for the treatment of acute spinal cord injury (SCI). The
biological rationale for the selection of each treatment modality is discussed
with reference to current knowledge of the principles in the management of acute
SCI as well as the primary and secondary injury mechanisms identified by
experimental and clinical studies of the pathophysiology of acute SCI. The trials
are evaluated with regard to the availability and use of accurate clinical
outcome measures, and the methodologies of the trials are critically evaluated
with an emphasis on prospective randomized controlled studies. A detailed
description and critical analysis are provided of the results of the 10 clinical
trials conducted to date in which a randomized prospective controlled design has
been used. The issue of the therapeutic time window in acute SCI is discussed. To
date, methylprednisolone is the only effective neuroprotective agent that has
been established for use in human SCI, and the only therapeutic time window
established in human SCI is a maximum trauma-to-treatment time of 8 hours.
PMID- 17031919
TI - A large protonated water cluster H+(H2O)27 in a 3D metal-organic framework.
AB - A large protonated water cluster, H+(H2O)27, has been trapped and stabilized
within the well-modulated cavity of a 3D metal-organic framework formed by
cobalt(II) and 4,4'-bipyridine-N,N'-dioxide with a globular Keggin structure
[PW12O4]3- anion as template. The structurally characterized protonated water
cluster might comprise a (H2O)26 shell with Oh symmetry and a monowater core
within the center which is suggested to be a hydronium ion with the Eigen model.
PMID- 17031920
TI - A ratiometric CdSe/ZnS nanocrystal pH sensor.
AB - The development of a reversible chemical sensor based on a CdSe/ZnS nanocrystal
(NC) is described. Signal transduction is accomplished by fluorescence resonance
energy transfer (FRET) between the NC and a fluorescent pH-sensitive squaraine
dye attached to the surface of the NC. The efficiency of FRET, and consequently
the relative intensity of NC and dye emissions, is modulated with the pH
dependent absorption cross section of the squaraine dye. The design of a NC
sensor based on FRET results in a ratiometric sensor since the emission
intensities of dye and NC may be referenced to the isosbestic point between NC
and dye emissions. The ratiometric approach allows sensing to be performed,
regardless of issues surrounding collection efficiency (scattering environment,
light fluctuations, etc.) and dye:NC loadings.
PMID- 17031921
TI - Enantioselectivity of redox reaction of DOPA at the gold electrode modified with
a self-assembled monolayer of homocysteine.
AB - The enantioselectivity of the self-assembled monolayer (SAM) of homocysteine
formed on the (111)-oriented gold surface was investigated. We analyzed the redox
behavior of 3,4-dihydroxyphenylalanine (DOPA), which is an electrochemically
active chiral molecule, by means of cyclic voltammetry at a gold electrode
modified with one enantiomeric form of homocysteine. It was demonstrated that the
homocysteine SAM of one enantiomeric form blocked the redox reaction of only one
enantiomer of DOPA, with cross inversion for the other enantiomer, in acidic
solution.
PMID- 17031922
TI - Aggregation of the amphipathic peptides (AAKA)n into antiparallel beta-sheets.
AB - Helical wheel projections of peptides based on the repeating unit Ac-(AAKA)n-NH2
clearly illustrate an amphipathic nature. One should therefore expect these
peptides to form helices if the number of residues exceeds a certain threshold
value. Indeed, ECD measurements show that Ac-(AAKA)4-NH2 and, to a minor extent,
also Ac-(AAKA)3-NH2 exhibit some helical content at millimolar concentrations in
aqueous solution. Surprisingly, however, these peptides were found to form
hydrogels with an antiparallel beta-sheet conformation at centimolar
concentrations. This occurs despite the positively charged lysine side chain
which would be expected to inhibit the formation of extended beta-sheet layers.
PMID- 17031923
TI - Determination of enantiomeric excess and concentration of unprotected amino
acids, amines, amino alcohols, and carboxylic acids by competitive binding assays
with a chiral scandium complex.
AB - A practical UV-vis sensing method for enantioselective microanalysis of
unprotected amino acids, amines, amino alcohols, and carboxylic acids in aqueous
solution has been developed. Both concentration and enantiomeric composition of a
wide range of chiral substrates can be determined with high accuracy by two
simple competitive binding assays using a scandium complex derived from 1,8-bis(3
(3',5'-dimethylphenyl)-9-acridyl)naphthalene N,N'-dioxide.
PMID- 17031924
TI - Palladium-catalyzed asymmetric [3 + 2] trimethylenemethane cycloaddition
reactions.
AB - Transition-metal-catalyzed trimethylenemethane (TMM) [3 + 2] cycloadditions
provide direct routes to functionalized cyclopentanes. This reaction has been
shown to be a highly chemo-, regio-, and diastereoselective process. We report a
palladium-catalyzed asymmetric [3 + 2] trimethylenemethane (TMM) cycloaddition
between 3-acetoxy-2-trimethylsilylmethyl-1-propene and various di- and
trisubstituted olefins. Yields of exo-methylenecyclopentane products range from
59 to 99%, and enantiomeric excesses range from 58 to 92% ee.
PMID- 17031925
TI - Gold nanoparticles propulsion from surface fueled by absorption of femtosecond
laser pulse at their surface plasmon resonance.
AB - Femtosecond laser irradiation of assembled nanoprisms on a quartz substrate at
their strong absorbing surface plasmon resonance frequency causes their
propulsion from the substrate. SEM and AFM show that the particles fly while
keeping their prismatic shape, but they decrease in size by an amount that can be
calculated assuming atomic sublimation. Several mechanisms are mentioned, but the
sublimation mechanism, which rapidly builds up pressure under the particle and
propels it away from substrate, is discussed in detail. From the kinetic energy
given to the flying nanoparticle, an initial velocity of approximately 160 m/s (
approximately 360 miles/h) is calculated. The dependence of the observed flying
mechanism on the rate of energy deposition (i.e., with nanosecond vs femtosecond
laser pulses) is discussed.
PMID- 17031926
TI - At least three contiguous atoms are necessary for CO formation during methanol
electrooxidation on platinum.
AB - We have used cyanide-modified Pt(111) electrodes to investigate the size and
geometry of the minimum atomic ensemble necessary for the oxidation of methanol
on Pt electrodes. Poison formation on cyanide-modified Pt(111) is completely
inhibited, the corresponding electrooxidation reaction proceeding, hence,
exclusively through the reactive intermediate pathway. These results suggest that
formation of adsorbed CO would require the presence of at least three contiguous
Pt atoms.
PMID- 17031927
TI - Infrared line shape of an alpha-carbon deuterium-labeled amino acid.
AB - The viability of alpha-carbon deuterated bonds (Calpha-D) as infrared (IR) probes
of protein backbone dynamics was explored through a combination of experiment and
theory. alpha-Carbon deuterated alanine (Ala-d1) served as a convenient model
system for a comparison of experiment, density functional theory (DFT), and
combined quantum mechanical/molecular mechanical (QM/MM) simulations of the
Calpha-D IR line shape. In addition to the primary Calpha-D absorption, the
experimental spectrum contains three features that likely result from Fermi
resonances. DFT calculations supported the assignments and identified the lower
frequency modes participating in the Fermi resonances. A QM/MM simulation of the
Ala-d1 line shape was in qualitative agreement with the experiment, including the
presence of classical analogues of Fermi resonances. These studies demonstrated
that the Calpha-D line shape is sensitive, via Fermi resonances, to lower
frequency collective vibrations that are expected to play a role in protein
dynamics and function, and that the QM/MM approach, which is applicable to
proteins, is capable of aiding in their interpretation.
PMID- 17031928
TI - An easy way to sugar-containing polymer vesicles or glycosomes.
AB - A thioglucose derivative was effectively grafted onto the double bonds of a 1,2
polybutadiene-block-polystyrene through photoaddition at room temperature. A so
prepared amphiphilic glycopolymer (17 wt % glucose) could be dispersed in organic
and in aqueous media, leading to the formation of sugar-containing polymer
vesicles or "glycosomes".
PMID- 17031929
TI - Synthesis of single- and double-walled carbon nanotube forests on conducting
metal foils.
AB - Here, we report a highly efficient growth of single-walled carbon nanotubes
(SWNTs) and double-walled carbon nanotubes (DWNTs) on conducting metal foils. We
found that foils made of Ni-based alloys with Cr or Fe serve as excellent
substrates for SWNT (DWNT) synthesis. In significant contrast, a CNT grown on Ni,
Fe foils contains a significant ratio of MWNTs. This result opens up an
economical route for the mass production of SWNT (DWNT) forests and also enables
the straightforward integration of CNTs into nanoelectronic devices, such as
field emission displays.
PMID- 17031930
TI - Iron-catalyzed [2pi + 2pi] cycloaddition of alpha,omega-dienes: the importance of
redox-active supporting ligands.
AB - The bis(imino)pyridine iron bis(dinitrogen) complex, (iPrPDI)Fe(N2)2 (iPrPDI =
2,6-(2,6-iPr2C6H3NCR)2C5H3N), serves as an efficient precursor for the catalytic
[2pi + 2pi] cycloaddition of alpha,omega-dienes to yield the corresponding
bicycles. For amine substrates, the rate of catalytic turnover increases with the
size of the nitrogen substituents, demonstrating competing heterocycle
coordination and product inhibition. In one case, a bis(imino)pyridine iron
azobicycloheptane product was characterized by X-ray diffraction. Preliminary
mechanistic studies highlight the importance of the redox activity of the
bis(imino)pyridine ligand to maintain the ferrous oxidation state throughout the
catalytic cycle.
PMID- 17031931
TI - Patterned metal nanowire arrays from photolithographically-modified templates.
AB - An effective procedure for the fabrication of patterned nanowire arrays with
micron-sized features is presented. Photolithographic methods are utilized to
form set patterns onto porous anodic alumina membranes (AAM), and these modified
membranes can then be used in the electrochemical growth of nanowire arrays. This
approach readily allows the formation of a variety of nanowire array patterns
with line widths down to several microns.
PMID- 17031932
TI - Complementary segmental labeling of large RNAs: economic preparation and
simplified NMR spectra for measurement of more RDCs.
AB - NMR structure determination of large RNAs is often restricted by limited RDC
information caused by chemical shift degeneracy. We established a general, time-
and cost-effective methodology for the preparation of 13C/15N complementary
labeled RNAs from a single plasmid. Applying this method to the 25 kDa BC1-DTE
RNA, we were able to resolve severe chemical shift degeneracy, thereby almost
doubling the number of RDC restraints in comparison to the conventional 13C,15N
uniform-labeled RNA.
PMID- 17031933
TI - Pyrones to pyrans: enantioselective radical additions to acyloxy pyrones.
AB - This paper describes a highly site-, diastereo-, and enantioselective
intermolecular radical addition/hydrogen atom transfer to hydroxypyrone
pyromeconic and kojic acids. The methodology can be extended to the formation of
chiral quaternary centers. The products obtained are densely functionalized pyran
moieties. The products contain structural features amenable for the introduction
of additional substituents.
PMID- 17031934
TI - Lipid encapsulation of arsenic trioxide attenuates cytotoxicity and allows for
controlled anticancer drug release.
AB - Arsenic trioxide (ATO, As2O3) is emerging as a front line agent for treatment of
acute promyelocytic leukemia with giving a complete remission rate of 83-95%. ATO
also shows significant activity in relapsed/refactory multiple myeloma; however,
efforts to expand clinical utility to other cancers have been limited by its
toxicity profile at higher doses. New bioavailable, liposome encapsulated As(III)
materials exhibit a significantly attenuated cytotoxicity that undergoes pH
triggered release of an active drug. The arsenic drugs are loaded into 100-nm
scale liposomes at high concentration (>270 mM) and excellent retention (shelf
life > 6 months at 4 degrees C), as determined by inductively coupled plasma
optical emission spectroscopy (ICP-OES), transmission electron microscopy (TEM),
and energy-dispersive X-ray (EDX) diffraction. In the loading mechanism, arsenous
acid crosses the bilayer membrane in exchange for acetic acid and an insoluble
transitional metal (e.g., Ni2+, Co2+) arsenite salt is formed. The resultant
liposomal arsenic nanoparticles appear to be stable in physiological situations
but release the drug cargo in a lower pH environment, as encountered in
intracellular endosomes. These drugs exhibit attenuated cytotoxicities against
human lymphoma tumor cells compared with that of free As2O3. Controlled release
of arsenic drugs, and hence control of toxicity, is feasible with this system.
The results demonstrate that cytotoxicity can be controlled via transitions of
the inorganic drug between solid and solution phases and suggest a mechanism for
further improvement of the risk/benefit ratio of As2O3 in treatment of a variety
of cancers.
PMID- 17031935
TI - Base and phosphate electron detachment energies of deoxyribonucleotide anions.
AB - Photoelectron spectra of deoxyribonucleotide anions are interpreted with ab
initio, electron propagator calculations. Ground-state structures display
hydrogen bonds which are not present in less stable minima that resemble Watson
Crick fragment geometries. For the adenosine and thymidine anions, there are two
vertical electron detachment energies (VEDEs) within 0.1 eV of each other that
correspond to phosphate- and base-centered Dyson orbitals (DOs). The first VEDE
of the cytidine anion belongs to a phosphate-centered DO. The anomalously low
VEDE of the guanosine anion is assigned to a base-centered, pi DO. Higher VEDEs
of all four anions also are assigned.
PMID- 17031936
TI - The elusive mechanism of olefin metathesis promoted by (NHC)Ru-based catalysts: a
trade between steric, electronic, and solvent effects.
AB - The reaction mechanism operative in olefin metathesis has been and still is a
challenging area of research. Here we contribute to the discussion showing that
the actual mechanism is a balance of the title effects. In particular, we show
that the electronic and solvent effects evidenced by experimental studies can be
easily counterbalanced by steric effects.
PMID- 17031937
TI - Layered oxysulfides Sr2MnO2Cu2m-0.5Sm+1 (m = 1, 2, and 3) as insertion hosts for
Li ion batteries.
AB - The layered oxysulfides Sr2MnO2Cu2m-0.5Sm+1 (m = 1-3) consist of alternating
perovskite-type Sr2MnO2 layers and copper sulfide layers. The copper ions can be
replaced electrochemically and reversibly by Li. The lithiated materials were
studied by Li MAS NMR, and Li resonances were observed with shifts that could be
rationalized based on the number of sulfide layers. The materials were cycled
versus Li and showed enhanced capacity retention in comparison to pure Cu2S; the
good electrochemical performance was ascribed to the presence of the layered
framework structure and rapid Li+ and Cu+ conductivity in the sulfide layers.
PMID- 17031938
TI - Site-specific conversion of cysteine thiols into thiocyanate creates an IR probe
for electric fields in proteins.
AB - The nitrile stretching mode of the thiocyanate moiety is a nearly ideal probe for
measuring the local electric field arising from the organized environment of the
interior of a protein. Nitriles were introduced into three proteins: ribonuclease
S (RNase S), human aldose reductase (hALR2), and the reaction center (RC) of
Rhodobacter capsulatus, through a facile synthetic scheme for the transformation
of cysteine residues into thiocyanatoalanine. Vibrational Stark effect
spectroscopy and Fourier transform infrared spectroscopy on the modified proteins
demonstrated that thiocyanate residues are a highly general tool for probing
electrostatic fields in proteins.
PMID- 17031939
TI - A biocompatible method of decorporation: bisphosphonate-modified magnetite
nanoparticles to remove uranyl ions from blood.
AB - We report on the use of bisphosphonate to functionalize Fe3O4 magnetic
nanoparticles via dopamine (DA) linkage. Using tetraethyl-3-aminopropane-1,1
bisphosphonate (BP) as the functional molecule, we created a system with an Fe3O4
DA-BP nanostructure, which possesses high specificity for removing uranyl ions
from water or blood. This work demonstrates that magnetic nanoparticles, combined
with specific receptor-ligand interactions, promise a sensitive and rapid
platform for the detection, recovery, and decorporation of metal toxins from
biological environment.
PMID- 17031940
TI - The open structure of a multi-drug-resistant HIV-1 protease is stabilized by
crystal packing contacts.
AB - The introduction of HIV-1 protease (HIV-PR) inhibitors has led to a dramatic
increase in patient survival; however, these gains are threatened by the
emergence of multi-drug-resistant strains. Design of inhibitors that overcome
resistance would be greatly facilitated by deeper insight into the mechanistic
events associated with binding of substrates and inhibitors, as well as an
understanding of the effects of resistance mutations on the structure and dynamic
behavior of HIV-PR. We previously reported a series of simulations that provide a
model for HIV-PR dynamics, with spontaneous conversions between the bound and
unbound crystal forms upon addition or removal of an inhibitor. Importantly, the
unbound protease transiently sampled a third fully open state that permits entry
to the active site, unlike both crystallographic forms. Recently, a crystal
structure of unbound HIV-PR was reported for the MDR 769 isolate (PDB: 1TW7);
unlike all previous experimental structures, the binding pocket is open. It is
suggested that drug resistance in this strain arises at least in part from the
inability of inhibitors to induce closing. We carried out simulations of the MDR
769 HIV-PR mutant and observed that the reported structure is unstable in
solution and rapidly adopts the semi-open conformation observed for the unbound
wild-type protease in solution. Further analysis suggests that the wide-open
structure observed for MDR 769 arises not from sequence variation, but instead is
an artifact from crystal packing. Thus, despite being the first experimental
structure to reveal flap opening sufficient for substrate access to the active
site, this structure may not be directly relevant to studies of inhibitor entry
or to the cause of HIV-PR drug resistance.
PMID- 17031941
TI - Dipolar control of monolayer morphology: spontaneous SAM patterning.
AB - A strategy for controlling relative placements of molecules within multicomponent
monolayers at the solution-HOPG interface is demonstrated. The monolayers
assemble from complementary pairs of 1,5-bis-alkyldiether-anthracenes bearing
self-repelling side chains. Each diether side chain suffers repulsive dipolar
interactions if it adsorbs next to an identical side chain in the morphology
normally assumed by 1,5-bis-substituted-anthracene monolayers. Complementary side
chain pairs experience attractive dipolar interactions when adsorbed as neighbors
in the normal morphology monolayer. The repulsive and attractive forces
spontaneously drive formation of a patterned monolayer at the solution-HOPG
interface. Each molecule adsorbs in its own row, sandwiched between two rows of
the complementary anthracene. These studies demonstrate the viability of using
weak dipolar interactions to control molecular placement and monolayer morphology
and to pattern multicomponent monolayers.
PMID- 17031942
TI - Unique aggregation of anthrax (Bacillus anthracis) spores by sugar-coated single
walled carbon nanotubes.
AB - There has been significant interest in the binding of anthrax spores by molecular
species, but with only limited success. Proteins and more recently peptides were
used. However, despite the known presence of carbohydrates on the spore surface,
carbohydrate-carbohydrate interactions have hardly been explored likely because
of the lack of required specific platform for synthetic carbohydrates. We report
the successful use of single-walled carbon nanotubes as a truly unique scaffold
for displaying multivalent monosaccharide ligands that bind effectively to
anthrax spores with divalent cation mediation to cause significant spore
aggregation. The work should have far-reaching implications in development of
countermeasure technologies.
PMID- 17031943
TI - Ligand-controlled, complementary stereoselectivity in the platinum-catalyzed
intramolecular silaboration of alkenes.
AB - An intramolecular silaboration of borylsilanyl homoallyl ethers was achieved
using a platinum catalyst, giving 1-oxa-2-silacyclopentanes in high yields. The
stereoselectivity of the reactions of sec-homoallyl ethers strongly depended on
the phosphorus ligand of the platinum catalysts used. The platinum complex
bearing the PCyPh2 ligand was found to be the most trans-selective catalyst
(trans/cis = 81:19-92:8), whereas a highly cis-selective cyclization was achieved
using a platinum catalyst having tris(2,4-di-tert-butylphenyl)phosphite ligand
(trans/cis = 8:92-6:94). The synthetic utility of the intramolecular silaboration
was demonstrated by the complementary synthesis of a pair of diastereomers of 6
methylheptane-1,3,5-triol.
PMID- 17031944
TI - Highly enantioselective transfer hydrogenation of alpha,beta-unsaturated ketones.
AB - We describe an efficient and highly enantioselective conjugate transfer
hydrogenation of alpha,beta-unsaturated ketones that is catalyzed by a salt made
from tert-butyl valinate and a recently introduced powerful chiral phosphoric
acid catalyst (TRIP).
PMID- 17031945
TI - Catalytic, enantioselective bifunctional inverse electron demand hetero-Diels
Alder reactions of ketene enolates and o-benzoquinone diimides.
AB - In this Communication, we report a system in which an achiral Lewis acid
(activating the diene) works in concert with a chiral nucleophile (dienophile) to
effect the first highly enantio- and regioselective catalytic inverse electron
demand Diels-Alder [4 + 2] cycloaddition reaction to form biologically active
quinoxalinones from ketene enolates and o-benzoquinone diimides in good to
excellent yields with >99% ee.
PMID- 17031946
TI - Multicolor microwave-triggered metal-enhanced chemiluminescence.
AB - We describe a novel platform technology for both significantly enhancing and
obtaining chemiluminescence signatures "on-demand", subsequently named Microwave
Triggered Metal-Enhanced Chemiluminescence. By combining the use of silver
nanoparticles to plasmon enhance chemiluminescence with the use of low power
microwaves to localize heating around the nanostructures, we can both optically
amplify and trigger chemiluminescence reactions. This approach is a significant
advantage over traditional chemiluminescence techniques and methodologies, such
as those used for Western Blots, which typically require long periods of time to
collect chemiluminescence and offer few possibilities of optically amplifying the
signatures.
PMID- 17031947
TI - Electrochemical real-time polymerase chain reaction.
AB - In this work, we report the first electrochemistry-based real-time polymerase
chain reaction technique for sequence-specific nucleic acid detection. This new
technique builds upon the advantages of the well-established fluorescence-based
counterpart, such as short assay time (simultaneous target DNA amplification and
detection). In addition, this electrochemical approach could employ simple and
miniaturizable instrumentation compared to the bulky and expensive optics
required in the fluorescence-based schemes. We have demonstrated a proof-of
concept experiment showing that the utilization of solid-phase extension of the
electrode surface-immobilized capture probe with Fc-dUTP during PCR resulted in
the accumulation of the redox marker on the transducer surface. This new
technique can be applied to a microfabricated PCR electrochemical device for
point-of-care diagnostics as well as on-site environmental monitoring and
biowarfare agent detection.
PMID- 17031948
TI - The design and investigation of room temperature thermotropic nematic gold
nanoparticles.
AB - Nematic gold nanoparticles, covered with a monolayer of calamitic mesogens and
short hydrocarbon chains, have been synthesized and investigated. The materials
are chemically stable and exhibit nematic phase behavior at room temperature.
PMID- 17031949
TI - Organic-organic epitaxy of incommensurate systems: quaterthiophene on potassium
hydrogen phthalate single crystals.
AB - Hot-wall epitaxy and molecular-beam epitaxy have been employed for growing
quaterthiophene thin films on the (010) cleavage face of potassium hydrogen
phthalate, and the results are compared in terms of film properties and growth
mode. Even if there is no geometrical match between substrate and overlayer
lattices, these films are epitaxially oriented. To investigate the physical
rationale for this strong orientation effect, optical microscopy, atomic force
microscopy, and X-ray diffraction are employed. A clear correlation between the
morphology of the thin films and the crystallographic orientation is found. The
results are also validated by surface potential calculations, which demonstrate
the primary role played by the corrugation of the substrate surface.
PMID- 17031950
TI - Thermal denaturing of mutant lysozyme with both the OPLSAA and the CHARMM force
fields.
AB - Biomolecular simulations enabled by massively parallel supercomputers such as
BlueGene/L promise to bridge the gap between the currently accessible simulation
time scale and the experimental time scale for many important protein folding
processes. In this study, molecular dynamics simulations were carried out for
both the wild-type and the mutant hen lysozyme (TRP62GLY) to study the single
mutation effect on lysozyme stability and misfolding. Our thermal denaturing
simulations at 400-500 K with both the OPLSAA and the CHARMM force fields show
that the mutant structure is indeed much less stable than the wild-type, which is
consistent with the recent urea denaturing experiment (Dobson et al. Science
2002, 295, 1719-1722; Nature 2003, 424, 783-788). Detailed results also reveal
that the single mutation TRP62GLY first induces the loss of native contacts in
the beta-domain region of the lysozyme protein at high temperatures, and then the
unfolding process spreads into the alpha-domain region through Helix C. Even
though the OPLSAA force field in general shows a more stable protein structure
than does the CHARMM force field at high temperatures, the two force fields
examined here display qualitatively similar results for the misfolding process,
indicating that the thermal denaturing of the single mutation is robust and
reproducible with various modern force fields.
PMID- 17031951
TI - Time-dependent photoluminescence blue shift of the quantum dots in living cells:
effect of oxidation by singlet oxygen.
AB - Time-dependent photoluminescence (PL) enhancement, blue shift, and photobleach
were observed from the thiol-capped CdTe quantum dots (QDs) ingested in mouse
myoblast cells and human primary liver cancer cells. It was revealed that the PL
blue shift resulted from the photooxidation of the QD core by singlet oxygen
molecules formed on the QD core surface.
PMID- 17031952
TI - Early events in the photochemistry of aryl azides from femtosecond UV/Vis
spectroscopy and quantum chemical calculations.
AB - The photochemistry of para- and ortho-biphenylyl azides and 1-naphthyl azide was
studied by ultrafast spectroscopy. In every case, the singlet azide second
excited states were observed by transient absorption spectroscopy and were found
to have lifetimes of hundreds of femtoseconds. The decay of the S(2) states of
the azides was accompanied by the growth of transient absorption of the
corresponding singlet nitrenes. The intermediate S(1) state of the azides could
not be observed due to its low instantaneous concentration resulting from fast
fragmentation and nitrene formation. Quantum chemical calculations predict that
the S(2) state of the azide is bound and that there is a much lower barrier
toward arylnitrene formation from the S(1) state of the azide. Vibrational
cooling of para-biphenylnitrene (11 ps) was experimentally observed. The lifetime
of singlet ortho-biphenylnitrene was 16 ps in acetonitrile and was not affected
by perdeuteration of the aryl ring. The lifetime of singlet 1-naphthylnitrene is
12 ps in acetonitrile at ambient temperature.
PMID- 17031953
TI - Dramatic acceleration of olefin epoxidation in fluorinated alcohols: activation
of hydrogen peroxide by multiple h-bond networks.
AB - In 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvent, the epoxidation of
olefins by hydrogen peroxide is accelerated up to ca. 100 000-fold (relative to
that in 1,4-dioxane as solvent). The mechanistic basis of this effect was
investigated kinetically and theoretically. The kinetics of the epoxidation of Z
cyclooctene provided evidence that higher-order solvent aggregates (rate order in
HFIP ca. 3) are responsible for the rate acceleration. Activation parameters
(DeltaS++ = -39 cal/mol.K) indicated a highly ordered transition state in the
rate-determining step. In line with these findings, DFT simulations revealed a
pronounced decrease of the activation barrier for oxygen transfer from H(2)O(2)
to ethene with increasing number of (specifically) coordinated HFIP molecules.
The oxygen transfer was unambiguously identified as a polar concerted process.
Simulations (combined DFT and MP2) of the epoxidation of Z-butene were in
excellent agreement with the experimental data obtained in the epoxidation of Z
cyclooctene (activation enthalpy, entropy, and kinetic rate order in HFIP of 3),
supporting the validity of our mechanistic model.
PMID- 17031955
TI - Why are ionic liquids liquid? A simple explanation based on lattice and solvation
energies.
AB - We have developed a simple and quantitative explanation for the relatively low
melting temperatures of ionic liquids (ILs). The basic concept was to assess the
Gibbs free energy of fusion (Delta(fus)G) for the process IL(s) --> IL(l), which
relates to the melting point of the IL. This was done using a suitable Born
Fajans-Haber cycle that was closed by the lattice (i.e., IL(s) --> IL(g)) Gibbs
energy and the solvation (i.e., IL(g) --> IL(l)) Gibbs energies of the
constituent ions in the molten salt. As part of this project we synthesized and
determined accurate melting points (by DSC) and dielectric constants (by
dielectric spectroscopy) for 14 ionic liquids based on four common anions and
nine common cations. Lattice free energies (Delta(latt)G) were estimated using a
combination of Volume Based Thermodynamics (VBT) and quantum chemical
calculations. Free energies of solvation (Delta(solv)G) of each ion in the bulk
molten salt were calculated using the COSMO solvation model and the experimental
dielectric constants. Under standard ambient conditions (298.15 K and 10(5) Pa)
Delta(fus)G degrees was found to be negative for all the ILs studied, as expected
for liquid samples. Thus, these ILs are liquid under standard ambient conditions
because the liquid state is thermodynamically favorable, due to the large size
and conformational flexibility of the ions involved, which leads to small lattice
enthalpies and large entropy changes that favor melting. This model can be used
to predict the melting temperatures and dielectric constants of ILs with good
accuracy. A comparison of the predicted vs experimental melting points for nine
of the ILs (excluding those where no melting transition was observed and two
outliers that were not well described by the model) gave a standard error of the
estimate (s(est)) of 8 degrees C. A similar comparison for dielectric constant
predictions gave s(est) as 2.5 units. Thus, from very little experimental and
computational data it is possible to predict fundamental properties such as
melting points and dielectric constants of ionic liquids.
PMID- 17031954
TI - Targeted acquisition for real-time NMR spectroscopy.
AB - A target-oriented approach for the acquisition of information in biomolecular NMR
spectroscopy is being developed. This approach combines concurrent data
accumulation, processing, and monitoring of spectral quality. Real-time
estimation of parameters allows acquisition to be stopped when results are
complete and have a specified precision. The technique is based on
multidimensional decomposition, which can process incomplete data. An incremental
nonuniform sampling scheme ensures the optimization of resolution sensitivity. To
validate this method, 3D HNCO spectra of three biomolecular systems (8 kDa
ubiquitin, 22 kDa barstar-barnase complex, and 82 kDa malate synthase G) are
processed incrementally at small acquisition time steps. The range of molecular
sizes illustrates applicability in both sample- and sensitivity-limited regimes.
In each case, the target was to acquire all backbone resonances in the spectra.
For the three systems, the targets are achieved after 4.5 min, 1.6 h, and 22 h of
acquisition time, respectively. A number of other targets that can be similarly
monitored as a function of time are discussed.
PMID- 17031956
TI - Free-energy landscape for beta hairpin folding from combined parallel tempering
and metadynamics.
AB - We develop a new free-energy method, based on the combination of parallel
tempering and metadynamics, and apply this method to the calculation of the free
energy landscape of the folding beta hairpin in explicit water. We show that the
combined method greatly improves the performance of both parallel tempering and
metadynamics. In particular, we are able to sample the high free-energy regions,
which are not accessible with conventional parallel tempering. We use our results
to calculate the difference in entropy and enthalpy between the folded and the
unfolded state and to characterize the most populated configurations in the
relevant free-energy basins.
PMID- 17031957
TI - A europium(III) complex as an efficient singlet oxygen luminescence probe.
AB - A new europium(III) complex, [4'-(10-methyl-9-anthryl)-2,2':6',2"-terpyridine
6,6"-diyl]bis(methylenenitrilo) tetrakis(acetate)-Eu(3+), was designed and
synthesized as a highly sensitive and selective time-gated luminescence probe for
singlet oxygen ((1)O2). The new probe is highly water soluble with a large
stability constant of approximately 10(21) and a wide pH available range (pH 3
10), and can specifically react with (1)O2 to form its endoperoxide (EP-MTTA
Eu(3+)) with a high reaction rate constant at 10(10) M(-1) s(-1), accompanied by
the remarkable increases of luminescence quantum yield from 0.90% to 13.8% and
lifetime from 0.80 to 1.29 ms, respectively. The wide applicability of the probe
was demonstrated by detection of (1)O2 generated from a MoO(4)(2-)/H(2)O2 system,
a photosensitization system of 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin
tetra(p-toluenesulfonate) (TMPyP), and a horseradish peroxidase catalyzed aerobic
oxidation system of indole-3-acetic acid (IAA). In addition, it was found that
the new probe could be easily transferred into living HeLa cells by incubation
with TMPyP. A time-gated luminescence imaging technique that can fully eliminate
the short-lived background fluorescence from TMPyP and cell components has been
successfully developed for monitoring the time-dependent generation of (1)O2 in
living cells.
PMID- 17031959
TI - Sorptive reconstruction of CuMCl4 (M = Al and Ga) upon small-molecule binding and
the competitive binding of CO and ethylene.
AB - Carbonyl adducts to CuMCl(4) (M = Al and Ga) have been characterized by single
crystal and/or powder X-ray diffraction, IR and diffuse reflectance UV/vis
spectroscopy. Up to two equivalents of carbon monoxide ( approximately 200
cm(3)/g relative to stp) are sorbed at room temperature, with equilibrium binding
pressures of below 0.5 atm of CO. The carbonyl bonding is shown to be
nonclassical, implicating the dominance of sigma-bonding and absence of pi-back
bonding. Analysis of the crystalline structures of the parent and adduct phases
provides an atomistic picture of the sorptive reconstruction reaction. Comparison
of the reactivity of CO and ethylene with these CuMCl(4) materials, as well as
other copper(I) halide compounds that exhibit classical and nonclassical modes of
bonding, demonstrates the ability to tune the reactivity of the crystalline
frameworks with selectivity for carbon monoxide or olefins, respectively.
PMID- 17031958
TI - Proline zwitterion dynamics in solution, glass, and crystalline state.
AB - Raman and Raman optical activity spectra of L- and D-proline zwitterionic (PROZW)
forms were recorded for H(2)O and D(2)O solutions in a wide frequency range and
analyzed with respect to the motion of the proline ring and rotation of the
carbonyl group. The solution spectra were additionally compared to Raman
scattering of glass and crystalline powder proline. Solution and glass spectral
band broadenings are similar and reveal information about the extent of internal
molecular motion. Two distinct but equally populated flexible forms were found in
the glass and the solution. The equal population is consistent with NMR data,
temperature, and concentration dependencies. The molecular flexibility is reduced
significantly in the crystal, however, where only one conformer is present.
Consequently, the crystal bands are narrow and exhibit minor frequency shifts.
The spectra were interpreted with the aid of density functional theory
computations involving both continuum and explicit solvent. A two-dimensional
potential energy surface pertaining to the five-member ring puckering coordinates
was constructed and used for dynamical averaging of spectral properties.
Comparison of the computed and experimental bandwidths suggests that the
puckering is strongly correlated with the carbonyl rotation. An averaging over
these two motions produces similar results. The interpretation of the Raman
experiments with the aid of the simulation techniques also indicates that the
environment modulates properties of the hydrophobic part of the molecule
indirectly by interacting with the ionic group. Such behavior may be important
for the reactivity and biological activity of proline-containing peptides and
proteins.
PMID- 17031960
TI - Sensitivity enhancement of multidimensional NMR experiments by paramagnetic
relaxation effects.
AB - One of the main goals of NMR method development is to increase the sensitivity of
multidimensional NMR experiments or reduce the required acquisition time. In
these experiments, more than 80% of the NMR instrument time is spent on the
recycle delay, where the instrument idles to wait for the recovery of proton
magnetization. In this study, we report a method of using paramagnetic relaxation
effects to shorten the recycle delays required in multidimensional NMR
experiments of biological macromolecules. This approach significantly reduces the
NMR instrument time required. Ni(2+) ion, complexed with the chelating molecule
DO2A, is used to decrease the proton T(1) relaxation time of biological
macromolecules without the significant line-broadening effects that are
associated with most paramagnetic ions. The Ni(DO2A) also significantly decreases
the T(1) relaxation time of water, thus providing additional sensitivity gain by
eliminating the saturation of labile amide resonances.
PMID- 17031961
TI - Characterization of self-assembled monolayers of fullerene derivatives on gold
surfaces: implications for device evaluations.
AB - The widely employed approach to self-assembly of fullerene derivatives on gold
can be complicated due to multilayer formations and head-to-tail assemblies
resulting from the strong fullerene-fullerene and fullerene-gold interactions.
These anomalies were not examined in detail in previous studies on fullerene self
assembled monolayers (SAMs) but were clearly detected in the present work using
surface characterization techniques including ellipsometry, cyclic voltammetry
(CV), and X-ray photoelectron spectroscopy (XPS). This is the first time that
SAMs prepared from fullerene derivatives of thiols/thiol esters/disulfides have
been analyzed in detail, and the complications due to multilayer formations and
head-to-tail assemblies were revealed. Specifically, we designed and synthesized
several fullerene derivatives based on thiols, thiol acetates, and disulfides to
address the characterization requirements, and these are described and
delineated. These studies specifically address the need to properly characterize
and control fullerene-thiol assemblies on gold before evaluating subsequent
device performances.
PMID- 17031962
TI - Hydrophobic and ionic interactions in nanosized water droplets.
AB - A number of situations such as protein folding in confined spaces, lubrication in
tight spaces, and chemical reactions in confined spaces require an understanding
of water-mediated interactions. As an illustration of the profound effects of
confinement on hydrophobic and ionic interactions, we investigate the solvation
of methane and methane decorated with charges in spherically confined water
droplets. Free energy profiles for a single methane molecule in droplets, ranging
in diameter (D) from 1 to 4 nm, show that the droplet surfaces are strongly
favorable as compared to the interior. From the temperature dependence of the
free energy in D = 3 nm, we show that this effect is entropically driven. The
potentials of mean force (PMFs) between two methane molecules show that the
solvent separated minimum in the bulk is completely absent in confined water,
independent of the droplet size since the solute particles are primarily
associated with the droplet surface. The tendency of methanes with charges (M(q+)
and M(q-) with q(+) = |q(-)| = 0.4e, where e is the electronic charge) to be
pinned at the surface depends dramatically on the size of the water droplet. When
D = 4 nm, the ions prefer the interior whereas for D < 4 nm the ions are
localized at the surface, but with much less tendency than for methanes.
Increasing the ion charge to e makes the surface strongly unfavorable. Reflecting
the charge asymmetry of the water molecule, negative ions have a stronger
preference for the surface compared to positive ions of the same charge
magnitude. With increasing droplet size, the PMFs between M(q+) and M(q-) show
decreasing influence of the boundary owing to the reduced tendency for surface
solvation. We also show that as the solute charge density decreases the surface
becomes less unfavorable. The implications of our results for the folding of
proteins in confined spaces are outlined.
PMID- 17031963
TI - Exchange coupling mediated through-bonds and through-space in conformationally
constrained polyradical scaffolds: calix[4]arene nitroxide tetraradicals and
diradical.
AB - Calix[4]arenes constrained to the 1,3-alternate conformation and functionalized
at the upper rim with four and two tert-butylnitroxides have been synthesized and
characterized by X-ray crystallography, magnetic resonance (EPR and (1)H NMR)
spectroscopy, and magnetic studies. The 1,3-alternate nitroxide tetraradical and
diradical provide unique polyradical scaffolds for dissection of the through-bond
and through-space intramolecular exchange couplings. In addition, detailed
magnetic studies of the previously reported calix[4]arene nitroxide tetraradical,
which possesses cone conformation in solution, reveal conformational dependence
of exchange coupling. Through-bond coupling between the adjacent nitroxide
radicals is mediated by the nitroxide-m-phenylene-CH(2)-m-phenylene-nitroxide
coupling pathway, and through-space coupling is found between the diagonal
nitroxide radicals at the conformationally constrained N...N distance of 5-6 A.
Magnetic studies of the calix[4]arene polyradical scaffolds in frozen solutions
show that the through-bond exchange coupling in the 1,3-alternate calix[4]arene
tetraradical is antiferromagnetic, while that in cone calix[4]arene tetraradical
is ferromagnetic. The through-space exchange couplings are antiferromagnetic in
both cone and 1,3-alternate calix[4]arene tetraradical, as well as in the 1,3
alternate calix[4]arene diradical. The exchange coupling constants (|J/k|) are of
the order of 1 K.
PMID- 17031964
TI - Residual dipolar couplings in short peptides reveal systematic conformational
preferences of individual amino acids.
AB - Residual dipolar couplings (RDCs) observed by NMR in solution under weak
alignment conditions can monitor average net orientations and order parameters of
individual bonds. By their simple geometrical dependence, RDCs bear particular
promise for the quantitative characterization of conformations in partially
folded or unfolded proteins. We have systematically investigated the influence of
amino acid substitutions X on the conformation of unfolded model peptides
EGAAXAASS as monitored by their (1)H(Nu)-(15)N and (1)H(alpha)-(13)C(alpha) RDCs
detected at natural abundance of (15)N and (13)C in strained polyacrylamide gels.
In total, 14 single amino acid substitutions were investigated. The RDCs show a
specific dependence on the substitution X that correlates to steric or
hydrophobic interactions with adjacent amino acids. In particular, the RDCs for
the glycine and proline substitutions indicate less or more order, respectively,
than the other amino acids. The RDCs for aromatic substitutions tryptophane and
tyrosine give evidence of a kink in the peptide backbone. This effect is also
observable for orientation by Pf1 phages and corroborated by variations in
(13)C(alpha) secondary shifts and (3)J(HNH)(alpha) scalar couplings in isotropic
samples. RDCs for a substitution with the beta-turn sequence KNGE differ from
single amino acid substitutions. Terminal effects and next neighbor effects could
be demonstrated by further specific substitutions. The results were compared to
statistical models of unfolded peptide conformations derived from PDB coil
subsets, which reproduce overall trends for (1)H(Nu)-(15)N RDCs for most
substitutions, but deviate more strongly for (1)H(alpha)-(13)C(alpha) RDCs. The
outlined approach opens the possibility to obtain a systematic experimental
characterization of the influence of individual amino acid/amino acid
interactions on orientational preferences in polypeptides.
PMID- 17031965
TI - Octahedral non-heme oxo and non-oxo Fe(IV) complexes: an experimental/theoretical
comparison.
AB - Electron-transfer series are described for three ferric complexes of the
pentadentate ligand 4,8,11-trimethyl-1,4,8,11-tetraazacyclotetradecane-1-acetate
(Me(3)cyclam-acetate) with axial chloride, fluoride, and azide ligands. These
complexes can all be reduced coulometrically to their Fe(II) analogs and oxidized
reversibly to the corresponding Fe(IV) species. The Fe(II), Fe(III), and Fe(IV)
species have been studied spectroscopically and their UV-vis, Mossbauer, EPR, and
IR spectra are presented. The fluoro species [(Me(3)cyclam-acetate)FeF](n+) (n =
0, 1, 2) have been studied computationally using density functional theory (DFT),
and the electronic structure of the Fe(IV) dication [(Me(3)cyclam
acetate)FeF](2+) is compared with that of the isoelectronic Fe(IV) oxo cation
[(Me(3)cyclam-acetate)FeO](+); the different properties of the two species are
mainly due to the significantly covalent Fe=O pi bonds in the latter.
PMID- 17031966
TI - Blood group B galactosyltransferase: insights into substrate binding from NMR
experiments.
AB - The biosynthesis of human blood group B antigens is accomplished by a highly
specific galactosyltransferase (GTB). On the basis of NMR experiments, we propose
a "molecular tweezers mechanism" that accounts for the exquisite
stereoselectivity of donor substrate selection. Transferred NOE experiments for
the first time reveal the bioactive conformation of the donor substrate UDP
galactose (UDP-Gal) and of its enzymatically inactive analogue, UDP-glucose (UDP
Glc). Both bind to GTB in a folded conformation that is sparsely populated in
solution, whereas acceptor ligands bind in a conformation that predominates in
solution. The bound conformations of UDP-Gal and UDP-Glc are identical within
experimental error. Therefore, GTB must discriminate between the two activated
sugars on the basis of a hitherto unknown transition state that can only be
formed in the case of UDP-Gal. A full relaxation and exchange matrix analysis of
STD NMR experiments reveals that acceptor substrates dissociate significantly
faster (k(off) > 100 Hz) from the binding pocket than donor substrates (k(off)
approximately 10 Hz). STD NMR experiments also directly show that proper
recognition of the hexopyranose rings of the UDP sugars requires bivalent metal
cations. At the same time, this analysis furnishes the complete three-dimensional
structure of the enzyme with its bound donor substrate UDP-Gal on the basis of a
prior crystal structure analysis. We propose that, upon acceptor binding, GTB
uses the Asp 302 and Glu 303 side chains as "molecular tweezers" to promote bound
UDP-Gal but not UDP-Glc into a transition state that leads to product formation.
PMID- 17031967
TI - Effects of the alternating backbone configuration on the secondary structure and
self-assembly of beta-peptides.
AB - Heterochiral homo-oligomers with alternating backbone configurations were
constructed by using the different enantiomers of the cis- and trans-2
aminocyclopentanecarboxylic acid (ACPC) monomers. Molecular modeling and the
spectroscopic techniques (NMR, ECD, and VCD) unequivocally proved that the
alternating heterochiral cis-ACPC sequences form an H10/12 helix, where extra
stabilization can be achieved via the cyclic side chains. The ECD and TEM
measurements, together with molecular modeling, revealed that the alternating
heterochiral trans-ACPC oligomers tend to attain a polar-strand secondary
structure in solution, which can self-assemble into nanostructured fibrils. The
observations indicate that coverage of all the possible secondary structures
(various helix types and strand-mimicking conformations) can be attained with the
help of cyclic beta-amino acid diastereomers. A relationship has been established
between the backbone chirality pattern and the prevailing secondary structure,
which underlines the role of stereochemical control in the beta-peptide secondary
structure design and may contribute to future biological applications.
PMID- 17031968
TI - Solid-state NMR of a paramagnetic DIAD-FeII catalyst: sensitivity, resolution
enhancement, and structure-based assignments.
AB - A general protocol for the structural characterization of paramagnetic molecular
solids using solid-state NMR is provided and illustrated by the characterization
of a high-spin Fe(II) catalyst precursor. We show how good NMR performance can be
obtained on a molecular powder sample at natural abundance by using very fast
(>30 kHz) magic angle spinning (MAS), even though the individual NMR resonances
have highly anisotropic shifts and very short relaxation times. The results
include the optimization of broadband heteronuclear (proton-carbon) recoupling
sequences for polarization transfer; the observation of single or multiple
quantum correlation spectra between coupled spins as a tool for removing the
inhomogeneous bulk magnetic susceptibility (BMS) broadening; and the combination
of NMR experiments and density functional theory calculations, to yield
assignments.
PMID- 17031969
TI - Photon gated transport at the glass nanopore electrode.
AB - The interior surface of the glass nanopore electrode was modified with spiropyran
moieties to impart photochemical control of molecular transport through the pore
orifice (15-90 nm radius). In low ionic strength acetonitrile solutions,
diffusion of a positively charged species (Fe(bpy)(3)(2+)) is electrostatically
blocked with approximately 100% efficiency by UV light-induced conversion of the
neutral surface-bound spiropyran to its protonated merocyanine form (MEH+).
Transport through the pore orifice is restored by either irradiation of the
electrode with visible light to convert MEH+ back to spiropyran or addition of a
sufficient quantity of supporting electrolyte to screen the electrostatic field
associated with MEH+. The transport of neutral redox species through spiropyran
modified glass nanopores is not affected by light, allowing photoselective
transport of redox molecules to the electrode surface based on charge
discrimination. The glass nanopore electrode can also be employed as a
photochemical trap, by UV light conversion of surface-bound spiropyran to MEH+,
preventing Fe(bpy)(3)(2+) initially in the pore from diffusing through the
orifice.
PMID- 17031970
TI - Energy-resolved photoionization of alkylperoxy radicals and the stability of
their cations.
AB - The photoionization of alkylperoxy radicals has been investigated using a newly
developed experimental apparatus that combines the tunability of the vacuum
ultraviolet radiation of the Advanced Light Source at Lawrence Berkeley National
Laboratory with time-resolved mass spectrometry. Methylperoxy (CH(3)OO) and
ethylperoxy (C(2)H(5)OO) radicals are produced by the reaction of pulsed,
photolytically produced alkyl radicals with molecular oxygen, and the mass
spectrum of the reacting mixture is monitored in time by using synchrotron
photoionization with a double-focusing mass spectrometer. The kinetics of product
formation is used to confirm the origins and assignments of ionized species. The
photoionization efficiency curve for CH(3)OO has been measured, and an adiabatic
ionization energy of (10.33 +/- 0.05) eV was determined with the aid of Franck
Condon spectral simulations, including ionization to the lowest triplet and
singlet cation states. Using the appearance energy of CH(3)(+) from CH(3)OO, an
enthalpy of formation for CH(3)OO of Delta(f) (CH(3)OO) = (22.4 +/- 5) kJ mol(-1)
is derived. The enthalpy of formation of CH(3)OO(+) is derived as Delta(f) =
(1019 +/- 7) kJ mol(-1) and the CH(3)(+)-OO bond energy as (CH(3)(+) - O(2)) =
(80 +/- 7) kJ mol(-1). The C(2)H(5)OO(+) signal is not detectable; however, the
time profile of the ethyl cation signal suggests its formation from dissociative
ionization of C(2)H(5)OO. Electronic structure calculations suggest that
hyperconjugation reduces the stability of the ethylperoxy cation, making the
C(2)H(5)OO(+) ground state only slightly bound with respect to the ground-state
products, C(2)H(5)(+) and O(2). The value of the measured appearance energy of
C(2)H(5)(+) is consistent with dissociative ionization of C(2)H(5)OO via the
Franck-Condon favored ionization to the a (1)A' state of C(2)H(5)OO(+).
PMID- 17031971
TI - Assisted desolvation as a key kinetic step for crystal growth.
AB - The crystallization of materials from a supersaturated solution is a fundamental
chemical process. Although several very successful models that provide a
qualitative understanding of the crystal growth process exist, in most cases the
atomistic detail of crystal growth is not fully understood. In this work,
molecular dynamics simulations of the morphologically most important surfaces of
barite in contact with a supersaturated solution have been performed. The
simulations show that an ordered and tightly bound layer of water molecules is
present on the crystal surface. The approach of an ion to the surface requires
desolvation of both the surface and the ion itself leading to an activated
process that is rate limiting for two-dimensional nucleation to occur. However,
desolvation on specific surfaces can be assisted by anions adsorbed on the
crystal surface. This hypothesis, corroborated by crystallization and scanning
electron microscopy studies, allows the rationalization of the morphology of
barite crystals grown at different supersaturations.
PMID- 17031972
TI - Neutral and zwitterionic low-coordinate titanium complexes bearing the terminal
phosphinidene functionality. Structural, spectroscopic, theoretical, and
catalytic studies addressing the Ti-P multiple bond.
AB - Alpha-hydrogen abstraction and alpha-hydrogen migration reactions yield novel
titanium(IV) complexes bearing terminal phosphinidene ligands. Via an alpha-H
migration reaction, the phosphinidene ((tBu)nacnac)Ti=P[Trip](CH(2)(tBu)
((tBu)nacnac(-) = [Ar]NC((t)Bu)CHC((t)Bu)N[Ar], Ar = 2,6-(CHMe2)(2C6H3, Trip =
2,4,6-(i)Pr3C6H2) was prepared by the addition of the primary phosphide
LiPH[Trip] to the nucleophilic alkylidene triflato complex
((tBu)nacnac)Ti=CH(t)Bu(OTf), while alpha-H abstraction was promoted by the
addition of LiPH[Trip] to the dimethyl triflato precursor
((tBu)nacnac)Ti(CH)(2)(OTf) to afford ((tBu)nacnac)Ti=P[Trip](CH3). Treatment of
((tBu)nacnac)Ti=P[Trip](CH3) with B(C6F5)(3) induces methide abstraction
concurrent with formation of the first titanium(IV) phosphinidene zwitterion
complex ((tBu)nacnac)Ti=P[Trip]{CH3B(C6F5)(3)}. Complex
((tBu)nacnac)Ti=P[Trip]{CH3B(C6F5)(3)} [2 + 2] cycloadds readily PhCCPh to afford
the phosphametallacyclobutene [((tBu)nacnac)Ti(P[Trip]PhCCPh)][CH3B(C6F5)(3)].
These titanium(IV) phosphinidene complexes possess the shortest Ti=P bonds
reported, have linear phosphinidene groups, and reveal significantly upfielded
solution 31P NMR spectroscopic resonances for the phosphinidene phosphorus. Solid
state 31P NMR spectroscopic data also corroborate with all three complexes
possessing considerably shielded chemical shifts for the linear and terminal
phosphinidene functionality. In addition, high-level DFT studies on the
phosphinidenes suggest the terminal phosphinidene linkage to be stabilized via a
pseudo Ti[triple bond]P bond. Linearity about the Ti-P-C(ipso) linkage is highly
dependent on the sterically encumbering substituents protecting the
phosphinidene. Complex ((tBu)nacnac)Ti=P[Trip]{CH3B(C6F5))(3)} can catalyze the
hydrophosphination of PhCCPh with H(2)PPh to produce the secondary vinylphosphine
HP[Ph]PhC=CHPh. In addition, we demonstrate that this zwitterion is a powerful
phospha-Staudinger reagent and can therefore act as a carboamination precatalyst
of diphenylacetylene with aldimines.
PMID- 17031973
TI - Effects of lysine acetylation in a beta-hairpin peptide: comparison of an amide
pi and a cation-pi interaction.
AB - The acetylation of lysine is a common posttranslational modification of histone
proteins, and the interaction of acetylated lysines with aromatic rings is
commonly observed in transcriptionally relevant protein-protein interactions. To
determine the nature of this interaction and its potential role in protein
structure and function, the effect of lysine acetylation on its interaction with
tryptophan has been investigated within the context of a beta-hairpin peptide.
Acetylation of Lys results in the replacement of a cation-pi interaction with an
amide-pi interaction. Despite the loss of positive charge, the interaction energy
is not significantly perturbed, although the geometry of interaction is
influenced such that the amide NH interacts directly with the Trp ring.
Thermodynamic analysis indicates an enthalpic driving force for the
stabilization, indicating a polar-pi interaction. Acyl lysine analogues formyl
lysine and trifluoroacetyl lysine were used to further investigate the sterics
and electronics of the interaction.
PMID- 17031974
TI - Color fingerprinting of proteins by calixarenes embedded in lipid/polydiacetylene
vesicles.
AB - "Naked eye" color detection of proteins was achieved by embedding calixarene
receptors within vesicles comprising phospholipids and the chromatic polymer
polydiacetylene. Dramatic visible absorbance changes were induced through
electrostatic interactions between the protein surface and the vesicle
incorporated hosts. The colorimetric responses could be induced by micromolar
protein concentrations, and furthermore, specific protein fingerprints could be
obtained by incorporating different receptors within the vesicles. Fluorescence
and circular dichroism experiments confirmed the relationship between the
colorimetric phenomena and protein docking on the surface of the chromatic
vesicles. The colorimetric assay constitutes a generic platform for high
sensitivity detection of soluble proteins and for evaluation of protein surface
charge distribution.
PMID- 17031975
TI - Kinetics and mechanism of ketone enolization mediated by magnesium
bis(hexamethyldisilazide).
AB - Magnesium bis(hexamethyldisilazide), Mg(HMDS)(2), reacts with substoichiometric
amounts of propiophenone in toluene solution at ambient temperature to form a
74:26 mixture of the enolates (E)- and (Z)-[(HMDS)(2)Mg(2)(mu-HMDS){mu
OC(Ph)=CHCH(3)}], (E)-1 and (Z)-1, which contain a pair of three-coordinate metal
centers bridged by an amide and an enolate group. The compositions of (E)-1 and
(Z)-1 were confirmed by solution NMR studies and also by crystallographic
characterization in the solid state. Rate studies using UV-vis spectroscopy
reveal the rapid and complete formation of a reaction intermediate, 2, between
the ketone and magnesium, which undergoes first-order decay with rate constants
independent of the concentration of excess Mg(HMDS)(2) (DeltaH++ = 17.2 +/- 0.8
kcal/mol, DeltaS++ = -11 +/- 3 cal/mol.K). The intermediate 2 has been
characterized by low-temperature (1)H NMR, diffusion-ordered NMR, and IR
spectroscopy and investigated by computational studies, all of which are
consistent with the formulation of 2 as a three-coordinate monomer,
(HMDS)(2)Mg{eta(1)-O=C(Ph)CH(2)CH(3)}. Further support for this structure is
provided by the synthesis and structural characterization of two model ketone
complexes, (HMDS)(2)Mg(eta(1)-O=C(t)Bu(2)) (3) and (HMDS)(2)Mg{eta(1)
O=C((t)Bu)Ph} (4). A large primary deuterium isotope effect (k(H)/k(D) = 18.9 at
295 K) indicates that proton transfer is the rate-limiting step of the reaction.
The isotope effect displays a strong temperature dependence, indicative of
tunneling. In combination, these data support the mechanism of enolization
proceeding through the single intermediate 2 via intramolecular proton transfer
from the alpha carbon of the bound ketone to the nitrogen of a bound
hexamethyldisilazide.
PMID- 17031976
TI - Thermodynamic and kinetic studies on the binding of nitric oxide to a new enzyme
mimic of cytochrome p450.
AB - A new model for the P450 enzyme carrying a SO(3)(-) ligand coordinated to
iron(III) (complex 2) reversibly binds NO to yield the nitrosyl adduct. The rate
constant for NO binding to 2 in toluene is of the same order of magnitude as that
found for the nitrosylation of the native, substrate-bound form of P450(cam) (E.S
P450(cam)). Large and negative activation entropy and activation volume values
for the binding of NO to complex 2 support a mechanism that is dominated by bond
formation with concomitant iron spin change from S = (5)/(2) to S = 0, as
proposed for the reaction between NO and E.S-P450(cam). In contrast, the
dissociation of NO from 2(NO) was found to be several orders of magnitude faster
than the corresponding reaction for the E.S-P450(cam)/NO system. In a
coordinating solvent such as methanol, the alcohol coordinates to iron(III) of 2
at the distal position, generating a six-coordinate, high-spin species 5. The
reaction of NO with 5 in methanol was found to be much slower in comparison to
the nitrosylation reaction of 2 in toluene. This behavior can be explained in
terms of a mechanism in which methanol must be displaced during Fe-NO bond
formation. The thermodynamic and kinetic data for NO binding to the new model
complexes of P450 (2 and 5) are discussed in reference to earlier results
obtained for closely related nitrosylation reactions of cytochrome P450(cam) (in
the presence and in the absence of the substrate) and a thiolate-ligated
iron(III) model complex.
PMID- 17031977
TI - Amorphous linear aliphatic polyesters for the facile preparation of tunable
rapidly degrading elastomeric devices and delivery vectors.
AB - A versatile method for preparing amorphous degradable elastomers with tunable
properties that can be easily fabricated into a wide variety of shape-specific
devices was investigated. Completely amorphous, liquid poly(ester ether)
prepolymers with number-average molecular weights between 4 and 6 x 10(3) g/mol
were prepared via condensation polymerization. These liquid prepolymers were then
thermally cross-linked to form degradable elastomeric structures. The ability to
vary the composition of these liquid prepolymers allows for easy control of the
mechanical and degradation properties of the resulting elastomeric structures.
Materials can be designed to completely degrade in vitro over a range of 30 days
to 6 months, while the Young's modulus can be varied over 3 orders of magnitude
(G = 0.02-20 MPa). Also, the liquid nature of these prepolymers makes them
amenable to a wide variety of fabrication techniques. Using traditional and
modified imprint lithography techniques, we have fabricated devices that
demonstrate a wide variety of biologically applicable topologies, which could
easily be extended to fabricate devices with more complex geometries. Until now,
no method has combined this ease and speed of fabrication with the ability to
control the mechanical and degradation properties of the resulting elastomers
over such a broad range.
PMID- 17031978
TI - Electronic structure and stability of pentaorganosilicates.
AB - The exceptional stability of recently reported pentaorganosilicates is
investigated by bond energy analyses. Experimental coupling constants are used to
probe their electronic structure, entailing bonds with mixed ionic-covalent
character. Our analyses reconfirm that the axial bonds are more prone to
heterolytic cleavage than are the equatorial bonds. Aryl substituents provide
substantial electronic stabilization by charge delocalization, but cause steric
crowding due to ortho-hydrogen repulsion. In contrast, silicates with two ax,eq
biaryl groups are not congested. The remaining substituent is confined to an
equatorial site, where it is insensitive to elimination. These concepts
adequately explain the experimentally observed stability trends and are valuable
for designing other stable pentaorganosilicates.
PMID- 17031982
TI - Quantum dynamical approach to ultrafast molecular desorption from surfaces.
PMID- 17031983
TI - Electronic excitations in metals and at metal surfaces.
PMID- 17031984
TI - Femtochemistry at metal surfaces: nonadiabatic reaction dynamics.
PMID- 17031979
TI - Racemization in Prins cyclization reactions.
AB - Isotopic labeling experiments were performed to elucidate a new mechanism for
racemization in Prins cyclization reactions. The loss in optical activity for
these reactions was shown to occur by 2-oxonia-Cope rearrangements by way of a
(Z)-oxocarbenium ion intermediate. Reaction conditions such as solvent,
temperature, and the nucleophile employed played a critical role in whether an
erosion in enantiomeric excess was observed. Additionally, certain structural
features of Prins cyclization precursors were also shown to be important for
preserving optical purity in these reactions.
PMID- 17031985
TI - Coherent vibrations of adsorbates induced by femtosecond laser excitation.
PMID- 17031986
TI - Dynamics of electronic transfer processes at metal/insulator interfaces.
PMID- 17031987
TI - Photoinduced electron transfer at molecule-metal interfaces.
PMID- 17031988
TI - Photochemistry on metal nanoparticles.
PMID- 17031989
TI - Patterned atomic reaction at surfaces.
PMID- 17031990
TI - Electronic control of single-molecule dynamics.
PMID- 17031991
TI - Photoreaction dynamics of molecular adsorbates on semiconductor and oxide
surfaces.
PMID- 17031992
TI - Solvated electrons on metal oxide surfaces.
PMID- 17031993
TI - Surface science studies of the photoactivation of TiO2--new photochemical
processes.
PMID- 17031994
TI - Confirmation of peanut protein using peptide markers in dark chocolate using
liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AB - Detection of peptides from the peanut allergen Ara h 1 by liquid chromatography
mass spectrometry (LC-MS) was used to identify and estimate total peanut protein
levels in dark chocolate. A comparison of enzymatic digestion subsequent to and
following extraction of Ara h 1 from the food matrix revealed better limits of
detection (LOD) for the pre-extraction digestion (20 ppm) than for the
postextraction digestion (50 ppm). Evaluation of LC-MS instruments and scan modes
showed the LOD could be further reduced to 10 ppm via a triple-quadrupole and
multiple-reaction monitoring. Improvements in extraction techniques combined with
an increase in the amount of chocolate extracted (1 g) improved the LOD to 2 ppm
of peanut protein. This method provides an unambiguous means of confirming the
presence of the peanut protein in foods using peptide markers from a major
allergen, Ara h 1, and can easily be modified to detect other food allergens.
PMID- 17031995
TI - Electrochemical estimation of the polyphenol index in wines using a laccase
biosensor.
AB - The use of a laccase biosensor, under both batch and flow injection (FI)
conditions, for a rapid and reliable amperometric estimation of the total content
of polyphenolic compounds in wines is reported. The enzyme was immobilized by
cross-linking with glutaraldehyde onto a glassy carbon electrode. Caffeic acid
and gallic acid were selected as standard compounds to carry out such estimation.
Experimental variables such as the enzyme loading, the applied potential, and the
pH value were optimized, and different aspects regarding the operational
stability of the laccase biosensor were evaluated. Using batch amperometry at
200 mV, the detection limits obtained were 2.6 x 10(-3) and 7.2 x 10(-4) mg L(-1)
gallic acid and caffeic acid, respectively, which compares advantageously with
previous biosensor designs. An extremely simple sample treatment consisting only
of an appropriate dilution of wine sample with the supporting electrolyte
solution (0.1 mol L(-1) citrate buffer of pH 5.0) was needed for the amperometric
analysis of red, rose, and white wines. Good correlations were found when the
polyphenol indices obtained with the biosensor (in both the batch and FI modes)
for different wine samples were plotted versus the results achieved with the
classic Folin-Ciocalteu method. Application of the calibration transfer
chemometric model (multiplicative fitting) allowed that the confidence intervals
(for a significance level of 0.05) for the slope and intercept values of the
amperometric index versus Folin-Ciocalteu index plots (r = 0.997) included the
unit and zero values, respectively. This indicates that the laccase biosensor can
be successfully used for the estimation of the polyphenol index in wines when
compared with the Folin-Ciocalteu reference method.
PMID- 17031996
TI - Determination of trace hydroxyl radicals by flow injection spectrofluorometry and
its analytical application.
AB - On the basis of the fluorescence increase of the reaction of ninhydrin with
hydroxyl radicals, a new method for the determination of trace amounts of
hydroxyl radicals by flow injection spectrofluorometry is presented. The
introduction of flow injection analysis brought better reproducibility and
avoided the effect of oxygen and other substances in the environment on the
reaction of ninhydrin with hydroxyl radicals. Under optimum experimental
conditions, the hydroxylated product of ninhydrin had excitation and emission
maxima at 300 and 406 nm, respectively. The linear range was 2.60 x 10(-7) to
4.00 x 10(-5) M, and the limit of detection was 7.91 x 10(-8) M. A high analysis
rate of 22 samples per hour was obtained. The proposed method has been applied
successfully to the determination of scavenging effects of thiourea and vitamin C
on hydroxyl radicals as well as to the evaluation of antioxidant capacities of
some natural food.
PMID- 17031997
TI - Evaluation of post-polymerase chain reaction melting temperature analysis for
meat species identification in mixed DNA samples.
AB - Real-time uniplex and duplex polymerase chain reaction (PCR) assays with a SYBR
Green I post-PCR melting curve analysis were evaluated for the identification and
quantification of bovine, porcine, horse, and wallaroo DNA in food products.
Quantitative values were derived from threshold-cycle (C(t)) data obtained from
serial dilutions of purified DNA. The limits of detection in uniplex reactions
were 0.04 pg for porcine and wallaroo DNA and 0.4 pg for cattle and horse DNA.
Species specificity of the PCR products was tested by the identification of peaks
in DNA melting curves, measured as the decrease of SYBR Green I fluorescence at
the dissociation temperature. The peaks could be distinguished above the
background even at the lowest amount of template DNA detected by the C(t) method.
The system was also tested in duplex reactions, by use of either single-species
DNA or DNA admixtures containing different shares of two species. The minimum
proportions of each DNA species allowing the resolution of T(m) peaks in the
duplex reactions were 5% (cattle or wallaroo) in cattle/wallaroo mixtures, 5%
porcine and 1% horse in porcine/horse mixtures, 60% porcine and 1% wallaroo in
porcine/wallaroo mixtures, and 1% cattle and 5% horse in cattle/horse mixtures. A
loss in the sensitivity of the method was observed for some DNA combinations in
the duplex assay. In contrast, the results obtained from SYBR Green I uniplex and
duplex reactions with single-species DNA were largely comparable to those
obtained previously with species-specific TaqMan probes, showing the suitability
of that simpler experimental approach for large-scale analytical applications.
PMID- 17031998
TI - Electromigration profiles of Cynomorium songaricum based on capillary
electrophoresis with amperometric detection.
AB - A high-performance capillary electrophoresis with amperometric detection (CE-AD)
method has been developed for the simultaneous determination of the
pharmacologically active ingredients in Cynomorium songaricum in this work. Under
the optimum conditions, phloridzin, epicatechin, catechin, naringenin, rutin,
luteolin, quercetin, gallic acid, and protocatechuic acid can be well separated
or nearly baseline separated (epicatechin and catechin peaks) within 31 min at
the separation voltage of 14 kV in a 50 mmol L(-1) Borax running buffer (pH 9.0).
Detection limits (S/N=3) ranged from 5.7 x 10(-8) to 8.5 x 10(-9) g mL(-1) for
all nine analytes. This procedure was successfully used for the analysis and
comparison of the content difference of C. songaricum samples collected from
different places based on their electrophorograms or "electromigration profiles".
PMID- 17031999
TI - Rapid quantification of the phenolic fraction of Spanish virgin olive oils by
capillary electrophoresis with UV detection.
AB - A rapid and reliable capillary zone electrophoresis method was used as a tool to
obtain both qualitative and quantitative information about simple phenols,
lignans, complex phenols (isomeric forms of secoiridoids), phenolic acids, and
flavonoids in the solid-phase separation extracts from different Spanish extra
virgin olive oil in a short time (less than 6 min). Peak identification was done
by using commercial and HPLC-isolated standards, studying the information of the
electropherograms obtained at several wavelengths and also using the information
previously reported. For the quantification of lignans and complex phenols
(secoiridoid derivatives), we used a reference compound (oleuropein glucoside) at
two different wavelengths (200 and 240 nm) and for the quantification of tyrosol
and flavonoids, we used their commercially available standards.
PMID- 17032000
TI - Evaluation of analytical methods for carotenoid extraction from biofortified
maize (Zea mays sp.).
AB - Biofortification of maize with beta-carotene has the potential to improve vitamin
A status in vitamin A deficient populations where maize is a staple crop.
Accurate assessment of provitamin A carotenoids in maize must be performed to
direct breeding efforts. The objective was to evaluate carotenoid extraction
methods and determine essential steps for use in countries growing biofortified
maize. The most reproducible method based on coefficient of variation and
extraction efficiency was a modification of Kurilich and Juvik (1999). Heat and
saponification are required to release carotenoids from biofortified maize and
remove oils interfering with chromatographic analysis. For maize samples with
high oil content, additional base may be added to ensure complete saponification
without compromising results. Degradation of internal standard before carotenoids
were released from the maize matrix required the addition of internal standard
after heating to prevent overestimation of carotenoids. This modified method
works well for lutein, zeaxanthin, beta-cryptoxanthin, alpha-carotene, and beta
carotene.
PMID- 17032001
TI - Spinach cultigen variation for tissue carotenoid concentrations influences human
serum carotenoid levels and macular pigment optical density following a 12-week
dietary intervention.
AB - Increasing intakes of carotenoid-rich plant foods can increase serum carotenoid
concentrations and macular pigment optical density (MPOD) in most, but not all,
individuals. Research objectives for this study were to (1) characterize tissue
lutein (L) and beta-carotene (BC) concentrations in carotenoid-rich spinach
(Spinacia oleracea L.) cultigens and (2) determine serum carotenoid and MPOD
responses in human subjects consuming spinach cultigens differing in tissue L and
BC concentrations. Thirteen spinach cultigens were evaluated for carotenoid
accumulations over two consecutive growing seasons. "Springer" (8.4 and 6.5
mg/100 g of fresh mass for L and BC, respectively) and "Spinner" (12.1 and 9.2
mg/100 g of fresh mass for L and BC, respectively) spinach cultigens were
selected for a dietary intervention study and represented low- and high-L
concentrations. The high-L ("Spinner") and low-L ("Springer" ) spinach treatment
groups consisted of 10 subject volunteers ingesting five 50-g spinach
servings/week during a 12-week intervention. Average serum L concentrations
increased by 22% (P = 0.07) from baseline (0.233 micromol/L) to 12 weeks (0.297
micromol/L) for subjects consuming low-L spinach. Subjects consuming high-L
spinach showed increases of 33% (P = 0.04) in serum L from baseline (0.202
micromol/L) to 12 weeks (0.300 micromol/L). Average MPOD did not change for the
low-L treatment group; however, subjects in the high-L group demonstrated
increases (P = 0.02) in MPOD at the 30' eccentricity between baseline (0.343) and
12 weeks (0.374). This study demonstrates that serum carotenoid and MPOD are
determined by L concentrations present in the spinach matrix. Results emphasize
the role of cultigen selection among vegetable crops in determining phytochemical
effects on human health.
PMID- 17032002
TI - Bioavailability of genistein and its glycoside genistin as measured in the portal
vein of freely moving unanesthetized rats.
AB - The present study describes an in vivo bioavailability experiment for genistein
and its glycoside genistin, either as pure compounds or from a soy protein
isolate extract, using freely moving unanesthetized rats with a cannulation in
the portal vein. The results show that genistein is readily bioavailable, being
observed in portal vein plasma at the first point of detection at 15 min after
dosing. The AUC(0-24h) values for total genistein and its conjugates were 54, 24,
and 13 microM h for genistein, genistin, and an enriched protein soy extract,
respectively. These results indicate that the bioavailability of genistein is
higher for the aglycon than for its glycoside. Genistin is partly absorbed in its
glycosidic form. It is concluded that bioavailability studies based on portal
vein plasma levels contribute to insight into the role of the intestine and liver
in deglycosylation and uptake characteristics of glycosylated flavonoids.
PMID- 17032003
TI - Bovine beta-casein (1-28), a casein phosphopeptide, enhances proliferation and IL
6 expression of mouse CD19+ cells via Toll-like receptor 4.
AB - This study was conducted to elucidate the target cells and receptors which
participate in the mitogenic and interleukin (IL)-6-enhancing effect of bovine
beta-casein (1-28), a casein phosphopeptide. When the spleen lymphocyte subset
(CD4+, CD8+, and CD19+ cells) from C3H/HeN mice was cultured with the beta-casein
(1-28), it exerted a dose-dependent mitogenic effect on CD19+ cells. The effect
of beta-casein (1-28) was not apparent in the case of CD19+ cells from C3H/HeJ
mouse. In addition, the effect was significantly inhibited by treating the
C3H/HeN mouse-derived CD19+ cells with neutralizing antibody for toll-like
receptor 4 (TLR4). Reverse transcription-polymerase chain reaction analysis
showed that the beta-casein (1-28) exerted an IL-6-enhancing effect on the CD19+
cells. The effect was also abrogated in either C3H/HeJ mouse-derived CD19+ cell
culture or the anti-TLR4 antibody-added culture. These results suggest that the
beta-casein (1-28) stimulates both proliferation and IL-6 expression of CD19+
cells via TLR4.
PMID- 17032004
TI - Oxidant/antioxidant properties of Croatian native propolis.
AB - Native propolis was defined as propolis powder collected from the continental
part of Croatia and prepared according to a patented process that preserves all
the propolis natural nutritional and organoleptic qualities. Nine phenolic
compounds (out of thirteen tested) in propolis sample were detected by high
performance liquid chromatography (HPLC) analysis. Among them chrysin was the
most abundant (2478.5 microg/g propolis). Contrary to moderate antioxidant
activity of propolis examined in vitro (ferric reduction antioxidant power; FRAP
assay), propolis as a food supplement modulated antioxidant enzymes (AOE) and
significantly decreased lipid peroxidation processes (LPO) in plasma, liver,
lungs, and brain of mice. The effect was dose- and tissue-dependent. The lower
dose (100 mg/kg bw) protected plasma from oxidation, whereas the higher dose (300
mg/kg bw) was pro-oxidative. Hyperoxia (long-term normobaric 100% oxygen)
increased LPO in all three organs tested. The highest vulnerability to oxidative
stress was observed in lungs where hyperoxia was not associated with augmentation
of AOE. Propolis protected lungs from hyperoxia by increased catalase (CAT)
activity. This is of special importance for lungs since lungs of adult animals
are highly vulnerable to oxidative stress because of their inability to augment
AOE activity. Because of its strong antioxidant and scavenging abilities, native
propolis might be used as a strong plant-based antioxidant effective not only in
physiological conditions but also in cases that require prolonged high
concentration of oxygen.
PMID- 17032005
TI - Influence of soy aglycon isoflavones on bone-related traits and lens protein
characteristics of ovariectomized rats and bioactivity performance of
osteoprogenitor cells.
AB - Health benefits of soy isoflavones have attracted the concern of the public and
the interest of health-care professionals. In this study, two trials were
conducted in characterizing bone-related traits and lens proteins as affected by
supplementation of soy aglycon isoflavones (SAI). In trial 1, an in vivo study,
20 Sprague-Dawley rats were ovariectomized (OVX) and randomly distributed into
OVX and OVX+SAI (135 mg of SAI/kg of feed; 8.33 mg/kg body weight; 2.5 mg/day)
groups. Another group containing 10 rats with a sham operation was control
(Sham). The experiment period was 3 months, and the rats were subjected to bone
related traits and lens protein characterization. In trial 2, an in vitro study,
osteoprogenitor cells (UMR-106) were divided into SAI-supplemented (0.5 mg of
SAI/mL of medium) and unsupplemented groups. Results of the in vivo study
indicated that daily BW gains in the OVX and OVX+SAI groups were greater than
that of the Sham group (p < 0.05). Bone ash and Ca contents of the Sham and
OVX+SAI groups were higher than those of the OVX group (p < 0.05), while bone
density, strength, and phosphorus contents among groups varied insignificantly (p
> 0.05). When the lens proteins were extracted and analyzed with size-exclusion
HPLC, the contents of beta- and gamma-crystallins were lowest in the OVX group
and the protein solubility decrease could be recovered by dietary SAI
supplementation (shown by OVX+SAI group). Based on Raman spectra of the isolated
lens proteins, disulfide bonds were observed more in OVX lens than in the Sham
and OVX+SAI lens. Results of in vitro study with osteoprogenitor cells revealed
that cell viability, alkaline phosphatase activity, osteocalcin, and Ca contents
of the SAI-supplemented group were higher than those of the unsupplemented group
(p < 0.05). The likely potency to enhance bone and lens health by SAI
supplementation is worth pointing out.
PMID- 17032006
TI - Polyphenolic profiles and antioxidant activities of heartnut (Juglans
ailanthifolia Var. cordiformis) and Persian walnut (Juglans regia L.).
AB - The polyphenolic compositions of three heartnut (Juglans ailanthifolia var.
cordiformis) varieties (Imshu, Campbell CW1, and Campbell CW3) were examined and
compared with those of two Persian walnut (Juglans regia L.) varieties (Combe and
Lake). The nuts were defatted, extracted, and separated into three different
fractions, the free phenolic acid (FPA), acid-hydrolyzable phenolic acid (AHPA),
and bound phenolic acid (BPA) fractions. The total phenolic contents (TPCs) in
both FPA and AHPA of the Persian walnuts were significantly higher (P < 0.001)
than those of the heartnuts, but not in the BPA (P = 0.20). LC-ESI-MS(n)()
studies revealed that except for the FPA fraction, the major polyphenolics in
both heartnut and Persian walnut were ellagic acid and valoneic acid dilactone.
Persian walnuts contained an average of 0.29 and 1.31 mg of ellagic acid/g nut in
the 80% methanol extractable fractions FPA and AHPA, respectively. Heartnuts
contained an average of 0.16 and 0.60 mg of ellagic acid/g nut in the respective
fractions. Bound ellagic acid in the residue was 0.93 and 0.70 mg/g of nut in the
Persian walnut and in the heartnut, respectively. Valoneic acid dilactone was
tentatively identified and quantified as milligrams of ellagic acid equivalent
per gram of nut. These components were found to contribute to the strong total
antioxidant activities measured using ferric reducing antioxidant power and
photochemiluminescence methods.
PMID- 17032007
TI - Production and characterization of human extracellular superoxide dismutase in
the methylotrophic yeast Pichia pastoris.
AB - Reactive oxygen species are associated with various diseases including
cardiovascular diseases, neurological disorders, and pulmonary diseases.
Extracellular superoxide dismutase (ECSOD) is an antioxidant enzyme secreted by
cells to prevent overproduction of reactive oxygen species. We expressed an ECSOD
gene isolated from a human aortic smooth muscle cDNA library in the
methylotrophic yeast Pichia pastoris. A synthetic secretion cassette was
constructed with the inducible promoter of the alcohol oxidase 1 gene (AOX1) and
the yeast alpha-mating factor signal peptide. As much as 25% of the total protein
was ECSOD in some transformants grown under inducing conditions. After 36 h of
methanol induction, ECSOD was exported into the culture medium at a concentration
of approximately 440 mg/L with an antioxidative activity of 760 +/- 20 U/mg
ECSOD. Transformed yeast cells were more resistant to heat shock and H(2)O(2)
oxidative stress, indicating that the human ECSOD expressed by P. pastoris had
multiple biological functions. Our data suggest that the methylotrophic yeast
inducible system is suitable for large-scale production of enzymatically active
human ECSOD.
PMID- 17032008
TI - Optimization of the extraction of antioxidative constituents of six barley
cultivars and their antioxidant properties.
AB - Response surface methodology (RSM) was used to predict the optimum conditions of
extraction of barley samples (organic solvent percent in the extraction medium,
temperature, and time). Antioxidant capacity in the barley meals was highest
under optimum extraction conditions of 80.2% methanol and 60.5 degrees C for
38.36 min as predicted by RSM. Phenolic antioxidative compounds of six barley
cultivars, namely, Falcon, AC Metcalfe, Tercel, Tyto, Phoenix, and Peregrine,
were extracted under the conditions obtained by RSM after defatting with hexane,
and subsequently the extracts were assessed for their antioxidant and antiradical
activities and metal chelation efficacy. The potential of barley extracts in
inhibiting peroxyl and hydroxyl radical induced supercoiled DNA double-strand
scission was also studied. Total phenolic content as measured according to Folin
Ciocalteu's method ranged from 13.58 to 22.93 mg of ferulic acid equiv/g of
defatted material, with the highest content in Peregrine. Total antioxidant
activity as measured by Trolox equivalent antioxidant capacity ranged from 3.74
to 6.82 micromol/g of defatted material. Metal chelation capacity of the extracts
as measured by 2,2'-bipyridyl competition assay varied from 1.1 to 2.1 micromol
of ethylenediaminetetraacetic acid equiv/g of defatted material. IC(50) values
for 1,1-diphenyl-2-picrylhydrazyl radical as measured by electron paramagnetic
resonance ranged from 1.51 to 3.33 mg/mL, whereas the corresponding values for
hydroxyl radical ranged between 2.20 and 9.65 mg/mL. Inhibition of peroxyl
radical induced supercoiled DNA scission ranged from 78.2 to 92.1% at the
concentration of 4 mg/mL of extracts, whereas the corresponding values for
hydroxyl radical induced DNA scission ranged from 53.1 to 65.3%.
PMID- 17032009
TI - Free radical scavenging effect of Pu-erh tea extracts and their protective effect
on oxidative damage in human fibroblast cells.
AB - In the present study, we successively extracted the Pu-erh tea with acetone,
water, chloroform, ethyl acetate, and n-butanol, and the extracts were then
isolated by column chromatography. Our study demonstrates that the Pu-erh tea
ethyl acetate extract, n-butanol extract, and their fractions had superoxide
anion and hydroxyl radical scavenging activity: fractions 2 and 8 from the ethyl
acetate extract and fractions 2, 4, and 5 from the n-butanol extract showed
protective effects against hydrogen peroxide-induced damage in human fibroblast
HPF-1 cells and increased the cells' viability under normal cell culture
conditions. In addition, it is found that these fractions, except fraction 5 from
the n-butanol extract, decreased the accumulation of intracellular reactive
oxygen species in hydrogen peroxide-induced HPF-1 cells. Interestingly, the
antioxidant effect of fraction 8 from the ethyl acetate extract on the above four
systems was much stronger than that of the typical green tea catechin (-)
epigallocatechin-3-gallate, but there were almost no monomeric polyphenols,
theaflavins, and gallic acid in fraction 8.
PMID- 17032010
TI - Secoisolariciresinol and matairesinol of sea buckthorn (Hippophae rhamnoides L.)
berries of different subspecies and harvesting times.
AB - Sea buckthorn (Hippophae rhamnoides) seeds, berries, and berry fractions are
often used as sources of bioactive ingredients for health products. The aim of
the present study was to analyze lignans in these fractions of sea buckthorn.
Secoisolariciresinol and matairesinol in seeds, fruit pulp/peel, and whole
berries of sea buckthorn of three subspecies were analyzed by isotope dilution
gas chromatography-mass spectrometry. The total content of the two lignans
secoisolariciresinol and matairesinol varied widely from 8 to 139 microg/100 g in
fresh berries and from 51 to 319 microg/100 g in dry berries. The content of
secoisolariciresinol varied in the range of 34-313 microg/100 g of dry mass in
the fruit pulp/peel and 93-355 microg/100 g in dry seeds. The content of
matairesinol fell within the range of 3-25 microg/100 g in dry pulp/peel and 1-13
microg/kg in dry seeds. Wild H. rhamnoides ssp. sinensis contained a
significantly higher total level of secoisolariciresinol and matairesinol in dry
seeds, dry berries, and fresh berries compared with wild ssp. rhamnoides (253 vs
135 microg/100 g, P < 0.01, in seeds; 224 vs 153 microg/100 g, P < 0.05, in dry
berries; 71 vs 29 g/100 g, P < 0.01, in fresh berries) and the cultivar of ssp.
mongolica (253 vs 112 microg/100 g in seeds, 71 vs 9 microg/100 g in fresh
berries). Harvesting dates had a significant influence on the content of the two
lignans in seeds, fruit pulp/peel, and whole berries. This is the first report of
lignans in sea buckthorn.
PMID- 17032011
TI - Chocolate is a powerful ex vivo and in vivo antioxidant, an antiatherosclerotic
agent in an animal model, and a significant contributor to antioxidants in the
European and American Diets.
AB - Chocolate today is often viewed as a food or snack with little nutritional value.
The high saturated fat content of chocolate has also contributed to the belief
that its consumption increases the risk of heart disease. However, recent human
studies have proven that chocolate has beneficial effects on some pathogenic
mechanisms of heart disease such as endothelial function and blood pressure.
Although the antioxidant properties of chocolate have been known for some time,
there has been no examination of its place in the U.S. diet as a source of
antioxidants. This paper demonstrates that chocolate makes a significant
contribution to U.S. per capita dietary antioxidants and by inference the
European Community's. In the U.S. diet chocolate is the third highest daily per
capita antioxidant source. An ex vivo study shows that epicatechin, a major
polyphenol in chocolate and chocolate extracts, is a powerful inhibitor of plasma
lipid oxidation due to polyphenols' ability to bind to lower density
lipoproteins. Conversely, the fat from chocolate alone is a pro-oxidant in this
model. This is also demonstrated in an in vivo human study. After consumption of
dark chocolate and cocoa powder, the lower density lipoproteins isolated from
plasma were protected from oxidation compared to the lipoproteins isolated after
cocoa butter consumption, which were put under oxidative stress. In an animal
model of atherosclerosis, cocoa powder at a human dose equivalent of two dark
chocolate bars per day significantly inhibited atherosclerosis, lowered
cholesterol, low-density lipoprotein, and triglycerides, raised high-density
lipoprotein, and protected the lower density lipoproteins from oxidation.
Chocolate has thus been shown to have potential beneficial effects with respect
to heart disease.
PMID- 17032012
TI - Properties of high-quality long natural cellulose fibers from rice straw.
AB - This paper reports the structure and properties of novel long natural cellulose
fibers obtained from rice straw. Rice straw fibers have 64% cellulose with 63%
crystalline cellulose, strength of 3.5 g/denier (450 MPa), elongation of 2.2%,
and modulus of 200 g/denier (26 GPa), similar to that of linen fibers. The rice
straw fibers reported here have better properties than any other natural
cellulose fiber obtained from an agricultural byproduct. With a worldwide annual
availability of 580 million tons, rice straw is an annually renewable, abundant,
and cheap source for natural cellulose fibers. Using rice straw for high-value
fibrous applications will help to add value to the rice crops, provide a
sustainable resource for fibers, and also benefit the environment.
PMID- 17032014
TI - Extraction of recombinant dog gastric lipase from transgenic corn seed.
AB - Several approaches were examined for extracting the relatively hydrophobic
protein recombinant dog gastric lipase (rDGL) expressed in the endosperm of
transgenic corn seed. The first approach used minimal processing of the seed
before extraction (i.e. simple grinding of whole seed) followed by selective
extraction to eliminate 72% of contaminant proteins without compromising rDGL
recovery from the meal of whole grain. The second approach added defatting of the
whole grain meal to reduce the amount of detergent in the subsequent step for
extracting rDGL. The third approach incorporated dry-milling of the corn to
recover an endosperm rich fraction, followed by extraction of this fraction. The
dry milling strategy was most effective, resulting in recovery of 35 U rDGL/g of
corn seed (50 U/g of endosperm) with a specific activity of 9 U/mg compared to 22
U and 3 U/mg for the first strategy and 36 U and 3.7 U/mg for the second. The
reductions in host protein contamination and lower detergent levels of the
endosperm route should simplify downstream purification steps.
PMID- 17032013
TI - High content of resveratrol in lettuce transformed with a stilbene synthase gene
of Parthenocissus henryana.
AB - Resveratrol (trans-3,5,4'-trihydroxystilbene) is a plant phytoalexin which has
positive effects on human health. Stilbene synthase (STS) is a key enzyme
involved in resveratrol biosynthesis. To construct a vector for STS expression in
lettuce plant, a cDNA-encoding STS of Parthenocissus henryana was fused to the
Cauliflower mosaic virus (CaMV) 35S promoter, and the bar gene was used as a
selective marker gene. To increase the expression of STS, the expression cassette
was flanked by MARs. In transgenic lettuce plants, an additional compound was
identified as resveratrol by HPLC and ESI-MS. Quantitative analysis showed that
the average content of resveratrol reached 56.40 +/- 5.52 microg/g leaf fresh
weight, which was comparable to the amount in grape skin. Anticancer assay in
HeLa cells revealed that apoptosis was induced by 200 microM of resveratrol
extracted from transgenic lettuce.
PMID- 17032015
TI - Reinvestigation of the effect of heat pretreatment of corn fiber and corn germ on
the levels of extractable tocopherols and tocotrienols.
AB - We previously reported that heat pretreatment of corn fiber (150 degrees C, 1 h)
caused a tenfold increase in the levels of extractable gamma-tocopherol. The
current study was a reinvestigation of the previous effect, using improved
methods (HPLC with fluorescence detection, diode-array UV detection, and mass
spectrometry) for tocol analysis. Heat pretreatment did not cause an increase in
the levels of any of the tocopherols or tocotrienols in corn fiber oil, but
lowered the levels of three of the tocols and had no effect on the levels of the
other two tocols. Heat pretreatment of corn germ had a similar effect. UV and
mass spectra indicated that the peak that we had identified as gamma-tocopherol
in our previous report was probably a mixture of oxidation products of
triacylglycerols. Thus, heat treatment of corn germ or other corn-oil containing
fractions at high temperatures leads to decreases in gamma-tocopherol, gamma
tocotrienol, and delta-tocotrienol and to the production of triacylglycerol
oxidation products.
PMID- 17032016
TI - Increase in the permeability of tonoplast of garlic (Allium sativum) by
monocarboxylic acids.
AB - Immersion of intact aged garlic (Allium sativum) cloves in a series of 5% weak
organic monocarboxylate solutions (pH 2.0) resulted in green color formation. No
color was formed upon treatment with other weak organic acids, such as citric and
malic acids, and the inorganic hydrochloric acid under the same conditions. To
understand the significance of monocarboxylic acids and their differing function
from that of other acids, acetic acid was compared with organic acids citric and
malic and the inorganic hydrochloric acid. The effects of these acids on the
permeability of plasma and intracellular membrane of garlic cells were measured
by conductivity, light microscopy, and transmission electron microscopy. Except
for hydrochloric acid, treatment of garlic with all three organic acids greatly
increased the relative conductivity of their respective pickling solutions,
indicating that all tested organic acids increased the permeability of plasma
membrane. Moreover, a pickling solution containing acetic acid exhibited 1.5-fold
higher relative conductivity (approximately 90%) as compared to those
(approximately 60%) of both citric and malic acids, implying that exposure of
garlic cloves to acetic acid not only changed the permeability of the plasma
membrane but also increased the permeability of intracellular membrane. Exposure
of garlic to acetic acid led to the production of precipitate along the
tonoplast, but no precipitate was formed by citric and malic acids. This
indicates that the structure of the tonoplast was damaged by this treatment.
Further support for this conclusion comes from results showing that the
concentration of thiosulfinates [which are produced only by catalytic conversion
of S-alk(en)yl-l-cysteine sulfoxides in cytosol by alliinase located in the
vacuole] in the acetic acid pickling solution is 1.3 mg/mL, but almost no
thiosulfinates were detected in the pickling solution of citric and malic acids.
Thus, all present results suggest that damage of tonoplast by treatment with
monocarboxylates such as acetic acid may be the main reason for the greening of
garlic.
PMID- 17032017
TI - Chemical composition and nutritional quality of soybean meals prepared by
extruder/expeller processing for use in poultry diets.
AB - This research examined variation in chemical composition and nutrient quality of
soybeans (SBs) and soybean meals (SBMs) produced at seven commercial
extruder/expeller plants in the United States (experiment 1), as well as
differences in amino acid digestibilities when roosters were fed SBMs extruded at
121, 135, 150, or 160 degrees C at a U.S. pilot processing plant (experiment 2).
In experiment 1, limited variation existed in the composition of SBs arriving at
the plants, whereas substantial differences were noted in amino acid composition
and protein quality of the resultant SBMs. In experiment 2, the SBMs extruded at
121 and 135 degrees C were underprocessed as noted by high urease activities and
lower amino acid digestibilities. Soybean meals extruded at 150 and 160 degrees C
resulted in higher amino acid digestibilities and lower urease activities,
indicating adequate processing. Large variation exists in the nutritional quality
of extruder/expeller SBMs currently in the marketplace. Optimal processing
temperatures should be >135 degrees C, and temperatures as high as 165 degrees C
do not result in overprocessing.
PMID- 17032018
TI - Influence of geographical origin and botanical species on the content of
extractives in American, French, and East European oak woods.
AB - The chemical composition of East European (Republic of Moldova, Ukraine, and
Romania) oaks was investigated profoundly for the first time in the present study
and compared with American and French counterparts. Taking into account the high
natural variability of oak extractives contents, the wide-ranging sampling was
performed for all oak origins: 276 French oaks, 102 East European oaks of both
species (Quercus robur L. and Quercus petraea Liebl.), and 56 American oaks
(Quercus alba). These oaks were compared with great attention paid to the
extractives, which are most important for sensorial impact in wine or spirit
maturation, such as ellagitannins and principal odorant substances (aromatic
aldehydes, lactones and phenols). The substances in question were studied by
application of HPLC and GC-MS techniques. The pattern of all studied extractive
contents allowed adequate separation of oak samples according to their
geographical origin or botanical species. The highest separation rate was for
American and French oaks, whereas East European samples could be partially
misclassified in two sets mentioned above. The most important variables for
species discrimination were whiskey lactone related variables and ellagitannins,
whereas the most important features for distinguishing the origin were eugenol, 2
phenylethanol, vanillin, and syringaldehyde. These substances allowed the
distinction of French and East European woods of the same species. With regard to
chemical composition, East European wood held the intermediary place between
American and French oaks according to their ellagitannin and whiskey lactone
levels; nevertheless, it was characterized by specific high values of eugenol,
aromatic aldehydes, and 2-phenylethanol.
PMID- 17032019
TI - Content of gamma-oryzanol and composition of steryl ferulates in brown rice
(Oryza sativa L.) of European origin.
AB - The content of gamma-oryzanol and the composition of steryl ferulates were
determined in brown rice of European origin using on-line coupled liquid
chromatography-gas chromatography (LC-GC). Analysis of 30 brown rice samples of
various cultivars, grown at different sites and in different seasons, revealed
the gamma-oryzanol content to range from 26 to 63 mg/100 g. Cycloartenyl ferulate
and 24-methylenecycloartanyl ferulate were the major components of gamma-oryzanol
followed by campesteryl ferulate, campestanyl ferulate, and beta-sitosteryl
ferulate. The proportions of individual steryl ferulates exhibited enormous
variability. However, irrespectively of the great variations observed for single
steryl ferulates, the proportions of the sum of 4,4'-dimethylsteryl ferulates
(cycloartenyl ferulate, 24-methylenecycloartanyl ferulate) and the sum of 4
desmethylsteryl ferulates (campesteryl ferulate, campestanyl ferulate, and beta
sitosteryl ferulate) were rather constant. The significant natural variability
observed for gamma-oryzanol content and composition of steryl ferulates were
shown to be influenced by environmental conditions but not by the degree of
maturity of rice grains.
PMID- 17032020
TI - Enantiomeric resolution and biotoxicity of methamidophos.
AB - Despite the fact that the biological processes of chiral pesticides are
enantioselective, the biotoxicity of methamidophos with respect to
enantioselectivity has so far received limited research. In this study, the
enantiomeric separation and biotoxicity of the two enantiomers of methamidophos
were investigated. Successful enantioseparation of methamidophos using high
performance liquid chromatography on a Chiralcel OD column was achieved. As
indicated by the optical rotation and circular dichroism detection, (+)
methamidophos was eluted prior to (-)-methamidophos. The t test at the 95% level
of confidence indicated significant differences between the enantiomers in their
in vitro inhibition toward acetylcholinesterases of bovine erythrocytes and
Electrophorus electricus and in vivo acute aquatic toxicity to Daphnia magna. The
in vitro assays showed that (-)-methamidophos was about 8.0-12.4 times more
potent to the enzymes than its (+)-form. In contrast, the (+)-enantiomer was 7.0
times more toxic to D. magna in 48 h tests. The toxicity of racemic methamidophos
was intermediate in both in vitro and in vivo bioassays. These results suggest
that the biotoxicity of chiral OPs to nontargeted organisms is enantioselective
and therefore should be reevaluated with their pure enantiomers.
PMID- 17032021
TI - Electrochemical investigation of the effect of pH and solvent on amitraz
stability.
AB - The widespread use of the pesticide amitraz for pest control of crops, livestock
and honeybees has warranted several studies aimed at understanding the
degradation of this compound during storage and use. In particular the
degradation of amitraz and the nature of the toxicologically significant
intermediates formed owing to pH and solvent type has been examined. In this
study we report on the use of electrochemical methods to monitor amitraz
degradation and to identify the major intermediates formed. While this study
examines the use of rapid voltammetric methods for such analyses, it also
resolves earlier studies showing the rapid degradation of amitraz to 2,4
dimethylaniline without formation of intermediates first, and also suggests that
the degradation of amitraz to 2,4-dimethylphenylformamide and to 2,4
dimethylaniline is more rapid than previously observed at pH above 3. These
studies also showed that amitraz degrades to dimethylphenylformamide in ethanol
and methanol, and is stable in both acetonitrile and dimethylsulphoxide.
PMID- 17032022
TI - Treatment of antibiotics and antibiotic resistant bacteria in swine wastewater
with free chlorine.
AB - Recent recognition of the occurrence of antibiotics in the environment has
highlighted concerns regarding potential threats of antibiotics to humans and
wildlife. Antibiotics are commonly applied to animals to prevent diseases and
promote growth, making livestock agriculture a major source of antibiotic
pollution. The purpose of our study was to examine chlorination technology as a
method for preventing the release of antibiotics as well as antibiotic-resistant
bacteria into the environment from concentrated animal feeding operations.
Wastewaters from various sites of two anaerobic lagoon systems, one aerated and
the other not, on a swine facility were investigated. Each system consisted of a
primary treatment lagoon and a subsequent polishing lagoon. Free chlorine (or
monochloramine for comparison) was applied to oxidize antibiotics and to
disinfect lagoon bacteria as well. Results indicate that aeration substantially
improves lagoon functionality, thereby adding both organic and ammonia removal.
Ammonia present in the wastewaters plays a critical role in antibiotics
decomposition and bacterial inactivation due to its rapid competition for free
chlorine to form monochloramine. Generally, a chlorine dose close to breakpoint
is required to achieve complete removal of antibiotics, leading to high
consumption of free chlorine in most of the wastewaters examined. However,
because of a low ammonia concentration in the polishing lagoon wastewater of the
aerated system, a chlorine dose of 100 mg/L can effectively achieve complete
removal of both antibiotics and bacteria. On the basis of our experimental
findings, a possible strategy for the treatment of swine wastewater is suggested.
PMID- 17032023
TI - Influence of pH and soil copper on adsorption of metalaxyl and penconazole by the
surface layer of vineyard soils.
AB - The upper horizons of old vineyard soils have substantial copper contents due to
the traditional use of copper-based fungicides. Total copper levels in eight
vineyard soils in the Rias Baixas area of Galicia (northwestern Spain) ranged
from 60 to 560 mg kg(-1) (mean +/- SD = 206 +/- 170 mg kg(-1)). The adsorption of
the fungicides metalaxyl (pK(a) = 1.41) and penconazole (pK(a) = 2.83) by these
soils was determined using fungicide solutions of pH 2.5 and 5.5, and desorption
of fungicide adsorbed at pH 5.5 was also determined. In all cases, Freundlich
equations were fitted to the data with R (2) > 0.96. Penconazole was adsorbed and
retained more strongly than metalaxyl, with K(F) values more than an order of
magnitude greater. In the desorption experiments, both fungicides exhibited
hysteresis. Soil copper content hardly affected the adsorption of metalaxyl, but
K(F) values for adsorption of penconazole increased at a rate of about 0.1 mL(n)
(microg of penconazole)(1-n) (microg of Cu)(-1), which is attributed to the
formation of Cu(2+)-penconazole complexes with greater affinity for soil colloids
than penconazole itself. Because the dependence of K(F) for penconazole
adsorption on copper content was the same at both pH values, complex formation
appears not to have been affected by the solubilization of 6-17% of soil copper
at pH 2.5. A similar copper dependence, or lack of dependence, was observed when
100-1000 mg kg(-1) of copper was added as Cu(NO(3))(2).2H(2)O to the solutions
from which the fungicides were adsorbed.
PMID- 17032024
TI - Sorption-desorption of imidacloprid and its metabolites in soil and vadose zone
materials.
AB - Sorption-desorption is one of the most important processes affecting the leaching
of pesticides through soil because it controls the amount of pesticide available
for transport. Subsurface soil properties can significantly affect pesticide
transport and the potential for groundwater contamination. This research
characterized the sorption-desorption of imidacloprid (1-[(6-chloro-3-pyridinyl)
methyl]-N-nitro-2-imidazolidinimine) and three of its metabolites, 1-[(6-chloro-3
pyridinyl)methyl]-2-imidazolidinone (imidacloprid-urea), 1-[(6-chloro-3
pyridinyl)methyl]-4,5-dihydro-1H-imidazol-2-amine (imidacloprid-guanidine), and 1
[(6-chloro-3-pyridinyl)methyl]-1H-imidazol-2-amine (imidacloprid-guanidine
olefin), as a function of changing soil properties with depth in two profiles
extending from the surface to a depth of 1.8 or 8 m. Sorption of each compound
was highly variable and hysteretic in all cases. Normalizing the sorption
coefficients (K(f)) to the organic carbon or the clay content of the soil did not
reduce the variability in sorption coefficients for any compound. These results
illustrate the importance of evaluation of the sorption data used to predict
potential mobility. Understanding the variability of soil properties and
processes as a function of depth is necessary for accurate prediction of
pesticide dissipation.
PMID- 17032025
TI - Reactions of hydrated electrons with triazine derivatives in aqueous medium.
AB - A study is made of the kinetics and mechanism of the reaction of radiolytically
produced hydrated electron (e-(aq)) with some triazine derivatives [1,3,5
triazine (T), 2,4,6-trimethoxy-1,3,5-triazine (TMT), 2,4-dioxohexahydro-1,3,5
triazine (DHT), 6-chloro N-ethyl N-(1-methylethyl)-1,3,5-triazine 2,4-diamine
(atrazine, AT), and cyanuric acid (CA)] in aqueous medium using pulse and steady
state radiolysis techniques. The second-order rate constants were determined from
the pseudo first-order decay of e(-)(aq) in the presence of triazines at 720 nm,
and the values obtained with T, TMT, AT, and CA are in the order of 10(9) dm(3)
mol(-1) s(-1) and that of DHT was 10(8) dm(3) mol(-1) s(-1) at pH 6. The
transient absorption spectra from the reaction of e(-)(aq) with T and TMT are
characterized by their lambda(max) at 310 nm, and those of DHT and CA are around
280 and 290 nm, respectively. However, a very weak and featureless absorption
spectrum is obtained from AT. On the basis of the spectral evidence and on the
quantitative electron transfer from the transient intermediates to the oxidant,
methyl viologen (MV(2+)), the intermediate radicals are assigned to N-protonated
electron adducts (with the unpaired spin density at carbon) of triazines. The
degradation profiles, monitored as the disappearance of parent triazine
concentrations as a function of dose, obtained with AT, TMT, CA, and DHT,
highlight the potential use of e-(aq) in the degradation of triazines.
PMID- 17032026
TI - Volatile compounds in the skin and pulp of Queen Anne's pocket melon.
AB - The quantitative distribution of volatile compounds in the skin and pulp of Queen
Anne's pocket melon [Cucumis melo var. dudaim (L.) Naudin] has been investigated.
Volatile compounds were extracted by liquid-liquid microextraction (LLME) using
chloroform and analyzed by GC-FID and GC-MS. Sixty volatiles, including 20
esters, 15 alcohols, 7 lactones, 7 aldehydes and ketones, 6 sulfur compounds, and
5 C(6) compounds, have been identified. Among them, 38 were reported for the
first time in pocket melon, 10 of them have been, however, labeled "tentatively
identified". The results showed that the levels of volatiles in skin were
significantly higher than those observed in pulp. Eugenol, the major constituent
in skin (15.3%), thioether esters, and lactones were thought to contribute
significantly to the unique aroma of the pocket melon. Finally, the distribution
of lactones was also found to be different in skin and pulp according to their
carbon chain length.
PMID- 17032027
TI - Rapid method for quantitative analysis of the aroma impact compound, 2-acetyl-1
pyrroline, in fragrant rice using automated headspace gas chromatography.
AB - A rapid method employing static headspace gas chromatography (HS-GC) has been
developed and validated for quantitative analysis of the impact aroma compound, 2
acetyl-1-pyrroline (2AP), in grains of fragrant rice. This developed method
excludes wet extraction, and the rice headspace volatiles are brought directly
and automatically to GC analysis. The conditions of the static HS autosampler
were optimized to achieve high recovery and sensitivity. The most effective
amount of rice sample used was 1 g, which provided 51% recovery and a linear
multiple headspace extraction (MHE) plot of the peak area of 2AP. The sensitivity
of the method was enhanced by utilizing a megabore fused silica capillary column
in conjunction with a nitrogen-phosphorus detector (NPD). Method validations
performed for both static HS-GC-FID and HS-GC-NPD demonstrated linear calibration
ranges of 20-10 000 (r(2) = 0.9997) and 5-8000 (r(2) = 0.9998) ng of 2AP/g of
rice sample, respectively. The limits of detection for both systems were 20 and 5
ng of 2AP, and the limits of quantitation were 0.30 and 0.01 g of brown rice
sample, respectively. Reproducibility calculated as intraday and interday
coefficients of variation were 3.25% RSD (n = 15) and 3.92% RSD (n = 35),
respectively, for SHS-GC-FID and 1.87% RSD (n = 15) and 2.85% RSD (n = 35),
respectively, for SHS-GC-NPD. The method was found to be effective when applied
to the evaluation of aroma quality, based on 2AP concentrations, of some fragrant
rice samples.
PMID- 17032028
TI - Characterization of volatiles in extracts from oak chips obtained by accelerated
solvent extraction (ASE).
AB - Sixteen commercially available oak chips, differing in origin (French or
American) and toasting level, were extracted by an accelerated solvent extraction
method and characterized by their volatile composition. About 80 compounds were
identified and quantified, a great part of them from the thermodegradation of
lignin and cellulose. One furanone (solerone) and two C-13 norisoprenoids (3-oxo
alpha-ionol and a 3-oxoretro-alpha-ionol isomer) were also tentatively identified
and reported for the first time in toasted wood. Quantitative data demonstrated
the oak chips to be not so different from the composition of light- or medium
toasted wood barrels, which was reported by other authors. The same data suggest
that toasting level had the strongest influence on the volatile composition of
chip samples. Phenyl ketones, volatile phenols, and some furanic compounds were
the most influenced. On the other hand, the influence of wood origin was found to
be weaker.
PMID- 17032029
TI - Volatile compound biosynthesis by green leaves from an Arabidopsis thaliana
hydroperoxide lyase knockout mutant.
AB - The degradation of polyunsaturated fatty acids through the lipoxygenase pathway
is responsible for the production of volatile compounds that confer green sensory
notes to the aroma of fruits and vegetables. The peroxidation of free linoleic or
linolenic acid by action of lipoxygenase and then the lysis of the resulting
hydroperoxides, through a reaction catalyzed by the hydroperoxide lyase, are the
most determinant steps of this pathway. This work analyzes the impact of the
hydroperoxide lyase depletion on the volatile composition of leaves from
Arabidopsis thaliana that is used as model system. The work involves the
characterization of the volatile profiles of the Arabidopsis plants followed by a
study of the metabolism of radio-labeled linoleic acid and determinations of
lipoxygenase activity. Hydroperoxide lyase-knockout plants show similar levels of
C6 compounds, but the total amount of C5 compounds is 4-fold higher in mutant
plants. The perspectives of production of vegetable products with a modified
aroma by genetically engineering the lipoxygenase pathway were discussed with
respect to the statistical results.
PMID- 17032030
TI - Cell wall composition of smooth bromegrass plants selected for divergent fiber
concentration.
AB - Neutral detergent fiber (NDF) is considered the single best laboratory predictor
of voluntary intake by ruminant livestock, creating interest in using NDF as a
selection criterion in forage breeding programs. Because genetic reductions in
NDF lead to increases in dry matter digestibility but not to changes in
digestibility of the NDF fraction, we postulated that low-NDF plants do not have
altered compositions of their cell walls. We tested this hypothesis using clones
of smooth bromegrass (Bromus inermis Leyss.) with divergent NDF concentrations.
High-NDF and low-NDF plants did not differ in cell wall concentrations or in the
concentrations of any cell wall component (fucose, arabinose, rhamnose,
galactose, glucose, xylose, mannose, uronic acids, and lignin). Instead, low-NDF
plants had a cell wall that was more susceptible to solubilization in neutral
detergent solution, suggesting that their cell walls were less well-developed as
compared to high-NDF plants. NDF should not be used as a substitute for cell wall
concentration in forage plants.
PMID- 17032031
TI - Inhibitory effect of known antioxidants and of press juice from herring (Clupea
harengus) light muscle on the generation of free radicals in human monocytes.
AB - Reactive oxygen species (ROS) can cause oxidative stress, which has been linked
to various diseases. It has been suggested that antioxidant-rich foods can reduce
such oxidative stress. However, the lack of suitable model systems to screen for
in vivo effects of food-derived antioxidants has prevented a clear consensus in
this area. In this study, the aim was to use a single-cell model system (human
monocyte) to evaluate whether certain pure antioxidants and complex muscle
extracts (herring light muscle press juice, PJ) could prevent ROS formation under
in vivo like conditions. ROS were excreted from the monocytes upon stimulation
with phorbol myristate acetate and were then detected as isoluminol-enhanced
chemiluminescence (CL). Adding 2000 units of catalase and 50 units of superoxide
dismutase to the monocytes model lowered the CL response by 35 and 86%,
respectively. Ascorbate (14.1 mM) lowered the response by 99%, alpha-tocoperhol
(188 microM) by 37%, and Trolox (50 microM) by almost 100%. Crude herring PJ gave
a dose-dependent reduction in the CL response. At 10, 100, and 1000 times
dilution, the PJ reduced the CL signal by 93, 60.5, and 10.6%. PJ fractionated
into low molecular weight (LMW) (<1000 Da) and high molecular weight (>3500 Da)
fractions decreased the CL response by 52.9 and 71.4%, respectively, at a 100
fold dilution. Evaluation of the PJ samples in the oxygen radical absorbance
capacity test indicated that proteins may be the primary radical scavenging
compounds of PJ, whereas the ROS-preventing effect obtained from the LMW fraction
may also be attributed to other mechanisms. Thus, this study proved that the
monocyte assay can be a useful tool for studying whether food-derived
antioxidants can limit ROS production under physiologically relevant conditions.
It also showed that herring contains numerous aqueous compounds demonstrating
antioxidative effects in the monocyte model system.
PMID- 17032032
TI - Molecular cloning and characterization of an alpha-amylase occurring in the pulp
of ripening bananas and its expression in Pichia pastoris.
AB - Alpha-amylases (EC 3.2.1.1) are glycosyl hydrolases with endoglycolytic activity
on the alpha-1,4-d-glucosidic linkages in starch. In bananas, the mobilization of
starch accounts for sugar accumulation during ripening, and among several
hydrolytic enzymes, alpha-amylase is the only enzyme argued to be able to attack
the intact granules, indicating a pivotal role for this enzyme. A 1953 bp full
length banana alpha-amylase cDNA (MAmy), encoded for a sequence of 416 amino
acids, was cloned and used for heterologous expression in Pichia pastoris. The
cloned MAmy presented the highly conserved motifs common to alpha-amylases, and
the amylolytic activity of the extracts from yeast transformed with MAmy
demonstrated that it encodes for a functional alpha-amylase, suggesting a
putative role for this gene in starch degradation during fruit ripening.
PMID- 17032033
TI - Starter bacteria are the prime agents of lipolysis in cheddar cheese.
AB - To assess the contribution of starter lactic acid bacteria (LAB) to lipolysis in
Cheddar cheese, the evolution of free fatty acids (FFAs) was monitored in Cheddar
cheeses manufactured from pasteurized milks with or without starter. Starter-free
cheeses were acidified by a combination of lactic acid and glucono-delta-lactone.
Starter cultures were found to actively produce FFAs in the cheese vat, and mean
levels of FFAs were significantly higher in starter cheeses over ripening. The
contribution of nonstarter LAB toward lipolysis appears minimal, especially in
starter-acidified cheeses. It is postulated that the moderate increases in FFAs
in Cheddar cheese are primarily due to lack of access of esterase of LAB to
suitable lipid substrate. The results of this study indicate that starter
esterases are the primary contributors to lipolysis in Cheddar cheese made from
good quality pasteurized milk.
PMID- 17032034
TI - Study of the effect of soy proteins on the acid-induced gelation of casein
micelles.
AB - The objective of this research was to understand whether addition of soy protein
to milk protein affects the properties of acid-induced casein gels. Different
samples were prepared by suspending casein micelles pellets in milk serum
containing soy proteins or whey proteins as well as mixtures of the two proteins.
Glucono-delta-lactone was added, and the changes in apparent size (in diluted
systems) as well as the viscoelastic properties of the mixtures were measured.
Size exclusion chromatography was also carried out to characterize the soluble
phase of the various mixtures before and after heating. Soy protein affected the
gelation of the mixtures; however, not to the same extent as whey proteins, which
dominated formation of the network in soy-whey-casein systems. It was concluded
that, up to a critical ratio of soy/whey proteins, soy proteins can be
incorporated in the mix without a significant change in structure of the casein
gels.
PMID- 17032035
TI - Three-year comparison of the content of antioxidant microconstituents and several
quality characteristics in organic and conventionally managed tomatoes and bell
peppers.
AB - Understanding how the environment and production and cultivation practices
influence the composition and quality of food crops is fundamental to the
production of high-quality nutritious foods. In this 3-year study, total
phenolics, percent soluble solids, ascorbic acid, and the flavonoid aglycones
quercetin, kaempferol, and luteolin were measured in two varieties of tomato
(Lycopersicon esculentum L. cv. Ropreco and Burbank) and two varieties of bell
peppers (Capsicum annuum L. cv. California Wonder and Excalibur) grown by
certified organic and conventional practices in a model system. Significantly
higher levels of percent soluble solids (17%), quercetin (30%), kaempferol (17%),
and ascorbic acid (26%) were found in Burbank tomatoes (fresh weight basis; FWB),
whereas only levels of percent soluble solids (10%) and kaempferol (20%) were
significantly higher in organic Ropreco tomatoes (FWB). Year-to-year variability
was significant, and high values from 2003 influenced the 3-year average value of
quercetin reported for organic Burbank tomatoes. Burbank tomatoes generally had
higher levels of quercetin, kaempferol, total phenolics, and ascorbic acid as
compared to Ropreco tomatoes. Bell peppers were influenced less by environment
and did not display cropping system differences.
PMID- 17032036
TI - Oxidative stability of algal oils as affected by their minor components.
AB - Algal oils, namely, arachidonic acid single-cell oil (ARASCO), docosahexaenoic
acid single-cell oil (DHASCO), and a single-cell oil rich in both docosahexaenoic
acid and docosapentaenoic acid (OMEGA-GOLD oil), were evaluated for their
oxidative stability, as such and after stripping of their minor components, in
the dark at 60 degrees C and under fluorescent light at 27 degrees C. Several
analytical methods were used to assess the oxidative stability of these oils. Oil
extracts were also investigated for their scavenging of 1,1-diphenyl-2
picrylhydrazyl radical by a spectrophotometric method and by measuring their
total phenolic contents. The results indicated that minor oil constituents play a
major role in their oxidative stability in the dark as well as under fluorescent
light. The stability of the oils was dictated by their fatty acid composition,
total tocopherols, and the type of pigment present. DHASCO contained a
significant level of natural radical scavengers and phenolic compounds that
contributed to its higher stability compared to the ARASCO and OMEGA-GOLD oils.
Thus, the importance of minor components in the stability of the oils examined
was demonstrated.
PMID- 17032037
TI - Comparative studies of some phenolic compounds (quercetin, rutin, and ferulic
acid) affecting hepatic fatty acid synthesis in mice.
AB - The physiological activities of some phenolic compounds affecting hepatic fatty
acid synthesis in mice were compared. Male ICR mice were fed an experimental diet
containing 1% quercetin dihydrate, rutin, or ferulic acid or a control diet free
of phenolic compounds for 15 days. Quercetin significantly lowered serum
cholesterol and phospholipid levels in mice. Also, the serum triacylglycerol
level was considerably lower in mice fed the quercetin-containing diet than in
those fed a diet free of phenolic compounds, although the difference was not
significant. Rutin and ferulic acid did not affect these parameters. Quercetin
significantly reduced the activity and mRNA levels of various enzymes involved in
hepatic fatty acid synthesis. Rutin reduced a few of the parameters for
lipogenesis, but ferulic acid did not affect any of the parameters. It was
suggested that a reduction in hepatic lipogenesis is the mechanism underlying the
hypolipidemic effect of quercetin.
PMID- 17032038
TI - Effectiveness of ionizing radiation in reducing furan and acrylamide levels in
foods.
AB - Furan and acrylamide are two possible carcinogens commonly found in many
thermally processed foods. The possibility of using ionizing radiation to reduce
the levels of thermally induced furan and acrylamide in water and selected foods
was investigated. Aqueous furan solutions, and foods (frankfurters, sausages,
infant sweet potatoes) that contained furan were irradiated to various doses of
gamma-rays. Water and oil spiked with acrylamide and potato chips (a known
acrylamide-containing food) were also irradiated. In addition, possible
irradiation-induced formation of acrylamide in glucose and asparagine solutions
was analyzed. Results showed that irradiation at 1.0 kGy destroyed almost all
furan in water. In frankfurters, sausages, and infant sweet potatoes, the rate of
irradiation-induced destruction of furan was much lower than the rate in water,
although significant reductions in furan levels were observed in all foods.
Irradiation at 2.5-3.5 kGy, doses that can inactivate 5-log of most common
pathogens, reduced furan levels in the food samples by 25-40%. Similarly to
furan, acrylamide in water was also sensitive to irradiation. After 1.5 kGy of
irradiation, most of the acrylamide was degraded. Irradiation, however, had a
very limited effect on acrylamide levels in oil and in potato chips, even at a
dose of 10 kGy. No detectable acrylamide was formed in the mixture of asparagine
and glucose upon irradiation. These results suggest that a low dose of
irradiation easily destroys furan and acrylamide in water. In real foods,
however, the reduction of furan was less effective than in water, whereas the
reduction in acrylamide was minimal.
PMID- 17032039
TI - Mechanisms of heme protein-mediated lipid oxidation using hemoglobin and
myoglobin variants in raw and heated washed muscle.
AB - The hemoglobin variant rHb 0.1, which possesses a decreased ability to form
subunits, stimulated lipid oxidation in washed fish muscle less effectively as
compared to wild-type hemoglobin (rHb 0.0). This could be due to the lower hemin
affinity and more rapid autoxidation rate of subunits as compared to tetramers.
To differentiate between hemin affinity and autoxidation effects, ferrous V68T Mb
was compared to ferrous wild-type myoglobin (WT Mb). WT Mb has a more rapid hemin
loss rate (25-fold) than does V68T, while V68T autoxidized more rapidly than did
WT Mb (60-fold). Ferrous WT Mb promoted TBARS and lipid peroxide formation more
rapidly than did ferrous V68T (p < 0.01). This indicated hemin loss rate was more
critical in determining onset of lipid oxidation as compared to autoxidation
rate. Hemin alone was capable of stimulating lipid oxidation. Albumin enhanced
the ability of hemin to promote lipid oxidation. MetMb promoted lipid oxidation
more effectively than did ferrous Mb, which could be due to the lower hemin
affinity of metMb as compared to that of ferrous Mb. EDTA, an iron chelator, had
no effect on the rate or extent of lipid oxidation mediated by Mb in the cooked
system. Variants with a 975-fold range of hemin affinities promoted lipid
oxidation with equivalent efficacy in cooked washed cod contrary to results in
uncooked washed cod. The cooking temperatures apparently denature the globin and
release hemin reactant to such an extent that the impact of hemin affinity on
lipid oxidation observed in the raw state is negated in the cooked state. These
studies collectively suggest released hemin is of primary importance in promoting
lipid oxidation in raw and cooked washed fish muscle.
PMID- 17032040
TI - Prediction of the ripening times of ewe's milk cheese by multivariate regression
analysis of capillary electrophoresis casein fractions.
AB - The effect of the ripening time on the proteolytic process in cheeses made from
ewe's milk during a 139-day ripening period was monitored by the use of capillary
electrophoresis of pH 4.6 insoluble fraction. Totals of 18 and 21 peaks were
recognized and matched in the electropherograms obtained with a fused-silica
capillary and a neutral capillary (hydrophilically coated), respectively. These
peaks correspond to intact ovine caseins and their hydrolysis products (alpha(s1)
casein I, alpha(s1)-casein II, alpha(s1)-casein III, alpha(s2)-casein, beta(1)
casein, beta(2)-casein, p-kappa-casein, alpha(s1)-I-casein, gamma(1)-casein,
gamma(2)-casein, and gamma(3)-casein). The alpha(s)-caseins (alpha(s1)- and
alpha(s2)-casein) displayed similar degradation pattern to one another, but
different from those of beta-caseins (beta(1)- and beta(2)-casein). beta-Caseins
were very much undergoing lesser degradation during the ripening time than
alpha(s)-casein. Finally, partial least-squares regression and principal
components regression were used to predict the ripening time in cheeses. The
models obtained yielded good results since the root-mean-square error in
prediction by cross validation was <8.6 days in all cases.
PMID- 17032041
TI - Solvent-mediated disruption of bovine casein micelles at alkaline pH.
AB - The disruption of casein micelles at alkaline pH was investigated using turbidity
measurements. The rate and extent of disruption of casein micelles at alkaline pH
(8.0-11.0) increased with pH. Furthermore, the extent of alkaline disruption
increased with increasing temperature (5-40 degrees C). Preheating milk for 10
min at 90 degrees C did not influence the extent of alkaline disruption of casein
micelles, suggesting that whey proteins do not influence the alkaline disruption
process. Levels of ionic calcium and serum calcium and phosphate decreased in a
logarithmic fashion with increasing pH, indicating precipitation of calcium
phosphate onto the casein micelles. A mechanism for alkaline disruption of casein
micelles is proposed, in which increasing the milk pH improves the solvent
quality for the caseins, thereby leading to the disruption of casein micelles
into their constituent nanoclusters; increases in the net-negative charge on the
caseins on increasing pH may contribute to micellar dissociation.
PMID- 17032042
TI - Interaction of sodium dodecyl sulfate with watermelon chromoplasts and
examination of the organization of lycopene within the chromoplasts.
AB - The properties of plant-derived precipitates of watermelon lycopene were examined
in aqueous sodium dodecyl sulfate (SDS) as part of an ongoing effort to develop
simpler, more economical ways to quantify carotenoids in melon fruit. Levels of
SDS >0.2% were found to increase the water solubility of lycopene in the state in
which it was isolated from watermelon. Electron microscopy and chemical analyses
suggested that the watermelon lycopene as isolated is packaged inside a membrane
to form a chromoplast. Spectral peaks in the visible region of the watermelon
chromoplasts in SDS exhibited a bathochromic shift from those in organic solvent.
Watermelon chromoplasts in SDS exhibited pronounced circular dichroic activity in
the visible region. Binding measurements indicated that about 120 molecules of
SDS were bound per molecule of lycopene inside the chromoplast; likely, the
detergent molecules are bound to the chromoplast membrane. Around 80% of the
chromoplast-SDS complexes were retained on a 0.45 mum membrane filter. Together,
these observations are consistent with lycopene in a J-type chiral arrangement
inside a membrane to form a chromoplast. The binding of SDS molecules to the
chromoplast membrane form a complex that is extensively more water-soluble than
the chromoplast alone.
PMID- 17032043
TI - Metabolite profiling of wheat grains (Triticum aestivum L.) from organic and
conventional agriculture.
AB - In some European community countries up to 8% of the agricultural area is managed
organically. The aim was to obtain a metabolite profile for wheat (Triticum
aestivum L.) grains grown under comparable organic and conventional conditions.
These conditions cannot be found in plant material originating from different
farms or from products purchased in supermarkets. Wheat grains from a long-term
biodynamic, bioorganic, and conventional farming system from the harvest 2003
from Switzerland were analyzed. The presented data show that using a high
throughput GC-MS technique, it was possible to determine relative levels of a set
of 52 different metabolites including amino acids, organic acids, sugars, sugar
alcohols, sugar phosphates, and nucleotides from wheat grains. Within the
metabolites from all field trials, there was at the most a 50% reduction
comparing highest and lowest mean values. The statistical analysis of the data
shows that the metabolite status of the wheat grain from organic and mineralic
farming did not differ in concentrations of 44 metabolites. This result indicates
no impact or a small impact of the different farming systems. In consequence, we
did not detect extreme differences in metabolite composition and quality of wheat
grains.
PMID- 17032044
TI - Enzymatic hydrolysis of flavonoids and pectic oligosaccharides from bergamot
(Citrus bergamia Risso) peel.
AB - Pectinolytic and cellulolytic enzymes (Pectinase 62L, Pectinase 690L, and
Cellulase CO13P) were used to evaluate the solubilization of carbohydrates and
low molecular weight flavonoids from bergamot peel, a major byproduct of the
essential oil industry. The enzymes were characterized for main-chain and side
chain polysaccharide hydrolyzing activities and also against pure samples of
various flavonoids previously identified in bergamot peel to determine various
glycosidase activities. The addition of Pectinase 62L or 690L alone, or the
combination of Pectinase 62L and Cellulase CO13P, was capable of solubilizing
between 70 and 80% of the bergamot peel, and up to 90% of the flavonoid
glycosides present were cleaved to their aglycones. Cellulase CO13P alone
solubilized 62% of the peel but had no deglycosylating effect on the flavonoid
glycosides. Over a 24-h time course, a rapid release of cell wall carbohydrates
was observed after treatment with Pectinase 62L, with a concurrent gradual
hydrolysis of the flavonoid glycosides. Size-exclusion chromatography of the
solubilized extract showed that after 24-h incubation, the majority of the
solubilized carbohydrates were present as monosaccharides with a smaller
proportion of oligosaccharides.
PMID- 17032045
TI - Chemical characterization of oak heartwood from Spanish forests of Quercus
pyrenaica (Wild.). Ellagitannins, low molecular weight phenolic, and volatile
compounds.
AB - The need for new sources of quality wood supply for cooperage has led to looking
into the possibility of utilizing Quercus pyrenaica Wild. oak, a species native
to the Iberian peninsula, as an alternative to other European (Quercus robur and
Qurecus petraea) and American (Quercus alba) oaks. The low molecular weight
phenolic composition, ellagitannins, and volatile compounds (including a wide
range of compound families such as volatile phenols, furanic compounds, lactones,
phenyl ketones, other lignin-derived compounds, and volatile compounds related to
off-flavors) of green heartwood from Spanish forest regions were studied by HPLC
and GC, in order to know its enological characteristics. The chemical composition
of Q. pyrenaica is similar to that of other species commonly used in cooperage to
make barrels, showing only quantitative differences that were more significant
with respect to American than to French species. The four provenance regions
studied showed similar chemical composition, with high variability among
individuals, often higher than the variability among regions of provenance, but
in line with that described in other European and American oak woods. Therefore,
this species must be considered to be suitable for aging wine.
PMID- 17032046
TI - Protein analysis of honeys by fast protein liquid chromatography: application to
differentiate floral and honeydew honeys.
AB - Fast protein liquid chromatography on a Superdex 75 HR column has been applied to
analyze the proteins of 29 honeys, 12 of floral origin and 17 from honeydew. The
molecular masses were comprised between 13100 and 94000 Da. Seven peaks have been
separated; four of them were present in all of the honeys, and three were only
present in some honeys. Direct observation of the chromatograms of the floral and
honeydew honeys did not reveal any information about their botanical origins.
However, both types of honeys can be distinguished with the percentages of the
areas of four of the seven chromatographic peaks obtained.
PMID- 17032047
TI - Flavonoids from italian multifloral honeys reduce the extracellular ferricyanide
in human red blood cells.
AB - In this study we investigated some biological properties of flavonoids recovered
in the aqueous (AqE) and ether (EtE) extracts from four Italian multifloral
honeys. In particular, a cell-free assay was employed to detect direct reduction
of ferricyanide, whereas an assay using intact human erythrocytes was used to
measure the ability to donate electrons to a trans-plasma membrane
oxidoreductase. It was found that the AqE displays greater "in vitro"
ferricyanide-reducing activity than the EtE but, unlike the latter, is virtually
ineffective in the cell-based assay. Uptake studies employing high-performance
liquid chromatography/mass spectrometry (HPLC/MS) showed that the different
results were explained by the inability of AqE components to cross the
erythrocyte plasma membrane and by the excellent uptake of EtE flavonoids, which,
once within the cell, donate electrons to the membrane oxidoreductase to
efficiently reduce extracellular oxidants. The latter property appears to depend
on the content of ether-soluble flavonoids in the starting honeys.
PMID- 17032048
TI - Changes in organic acids and sugars during early stages of development of acidic
and acidless citrus fruit.
AB - Most of the studies on organic acids and sugars in citrus were performed during
fruit maturation, and less is known before this stage of development. The aim of
our study was to investigate acids and sugars in lemon, lime, and orange from
fruit-set toward development. We chose to compare organic acid and sugar
accumulation among acidic and acidless varieties within three species. We
estimated the acidity by titrimetry and quantified the concentrations of seven
organic acids and three sugars by reverse HPLC. During the first 50 days of
development, quinic acid was the major organic acid whatever the variety.
Afterward, citric acid predominated in acidic varieties, while in acidless, malic
acid exceeded it. Fructose substituted citric acid in acidless and could be
synthesized either from citric acid or directly from glucose. Our results
provided the first complete report on sugar and organic acid accumulation during
the early stages of fruit development in several citrus varieties.
PMID- 17032049
TI - Selective recovery of tagatose from mixtures with galactose by direct extraction
with supercritical CO2 and different cosolvents.
AB - A selective fractionation method of carbohydrate mixtures of galactose/tagatose,
using supercritical CO(2) and isopropanol as cosolvent, has been evaluated.
Optimization was carried out using a central composite face design and
considering as factors the extraction pressure (from 100 to 300 bar), the
extraction temperature (from 60 to 100 degrees C), and the modifier flow rate
(from 0.2 to 0.4 mL/min, which corresponded to a total cosolvent percentage
ranging from 4 to 18% vol). The responses evaluated were the amount (milligrams)
of tagatose and galactose extracted and their recoveries (percent). The
statistical analysis of the results provided mathematical models for each
response variable. The corresponding parameters were estimated by multiple linear
regression, and high determination coefficients (>0.96) were obtained. The
optimum conditions of the extraction process to get the maximum recovery of
tagatose (37%) were 300 bar, 60 degrees C, and 0.4 mL/min of cosolvent. The
predicted value was 24.37 mg of tagatose, whereas the experimental value was
26.34 mg, which is a 7% error from the predicted value. Cosolvent polarity
effects on tagatose extraction from mixtures of galactose/tagatose were also
studied using different alcohols and their mixtures with water. Although a
remarkable increase of the amount of total carbohydrate extracted with polarity
was found, selective extraction of tagatose decreased with increase of polarity
of assayed cosolvents. To improve the recovery of extracted tagatose, additional
experiments outside the experimental domain were carried out (300 bar, 80 degrees
C, and 0.6 mL/min of isopropanol); recoveries >75% of tagatose with purity >90%
were obtained.
PMID- 17032050
TI - Different effects of microwave and ultrasound on the stability of (all-E)
astaxanthin.
AB - Both microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE)
have been widely applied in the extraction of a variety of biologically active
compounds including carotenoids due to their lower pollution to environment, high
extraction efficiency, lower cost, and shorter extraction time as compared to
conventional extraction techniques. However, there are few reports on their
effects on the stability of these compounds. In the present study, the stability
of (all-E)-astaxanthin, one of the carotenoids, was examined under the action of
both ultrasound and microwave. Results showed that microwave induced the
isomerization of (all-E)-astaxanthin to its Z analogues, preferentially to (13Z)
astaxanthin as analyzed by HPLC coupled with diode array detection and LC-MS; and
the percentage of the isomerization increased with increasing both treatment time
and microwave power. In contrast to the microwave, the ultrasound degraded (all
E)-astaxanthin to unidentified colorless compound(s) as suggested by HPLC
analysis and UV/vis measurements, and the degradation likewise increased as both
treatment time and ultrasonic power increased. The results presented here
emphasized that both MAE and UAE techniques should be carefully used in the
extraction of unstable compounds such as (all-E)-astaxanthin.
PMID- 17032051
TI - NMR characterization of lignins isolated from fruit and vegetable insoluble
dietary fiber.
AB - Compositional information for lignins in food is rare and concentrated on cereal
grains and brans. As lignins are suspected to have important health roles in the
dietary fiber complex, the confusing current information derived from nonspecific
lignin determination methods needs to be augmented by diagnostic structural
studies. For this study, lignin fractions were isolated from kiwi, pear, rhubarb,
and, for comparison, wheat bran insoluble dietary fiber. Clean pear and kiwi
lignin isolates allowed for substantive structural profiling, but it is suggested
that the significance of lignin in wheat has been overestimated by reliance on
nonspecific analytical methods. Volume integration of NMR contours in two
dimensional (13)C-(1)H correlation spectra shows that pear and wheat lignins have
comparable guaiacyl and syringyl contributions and that kiwi lignins are
particularly guaiacyl-rich (approximately 94% guaiacyl) and suggest that rhubarb
lignins, which could not be isolated from contaminating materials, are as
syringyl-rich (approximately 96% syringyl) as lignins from any known natural or
transgenic fiber source. Typical lignin structures, including those newly NMR
validated (glycerols, spirodienones, and dibenzodioxocins), and resinols
implicated as possible mammalian lignan precursors in the gut are demonstrated
via their NMR correlation spectra in the fruit and vegetable samples. A novel
putative benzodioxane structure appears to be associated with the kiwi lignin. It
is concluded that the fruits and vegetables examined contain authentic lignins
and that the detailed structural analysis exposes limitations of currently
accepted analytical methods.
PMID- 17032052
TI - Effect of bread baking on the bioavailability of hydrogen-reduced iron powder
added to unenriched refined wheat flour.
AB - Elemental iron powders are widely used to fortify flour and other cereal
products. Our objective was to test the hypothesis that baking enhances the
bioavailability of elemental iron powders by oxidizing Fe(0) to Fe(2+) or Fe(3+).
An in vitro digestion/Caco-2 cell culture model and a piglet model were used to
measure bioavailability. Bread flour, either unfortified or fortified with
hydrogen-reduced (HR) iron powder or FeSO(4) (300 mg Fe/kg flour), was baked into
bread. For the in vitro studies, bread samples were treated with pepsin at pH 2,
3, 4, 5, 6, or 7 and subsequently incubated with pancreatic enzymes at pH 7 in a
chamber positioned above monolayers of cultured Caco-2 cells. Ferritin formation
in the cells was used as an index of iron bioavailability. Ferritin formation in
cells fed HR Fe bread was similar to cells fed FeSO(4) bread when the peptic
digestion was conducted at a pH 2 but lower when the peptic phase was conducted
at pH 3, 4, 5, 6, or 7 (P < 0.05). Pig diets containing 35% dried bread were
prepared and fed to cross-bred (Hampshire x Landrace x Yorkshire) anemic pigs in
two studies. The rate of increase in hemoglobin Fe over the feeding period was
used to calculate relative biological value (RBV), an index of iron
bioavailability. In the first pig study, RBV of HR Fe added to flour prior to
baking was 47.9% when compared to FeSO(4) fortified flour (P < 0.05). In the
second pig study, a third treatment consisting of unfortified bread with HR iron
added during diet mixing (after bread baking) was included. RBVs of the HR Fe
diet (Fe added after baking) and HR Fe diet (Fe added before baking) were 40.1%
and 53.5%, respectively, compared to the FeSO(4) diet. Differences in RBV between
the HR Fe (before and after baking) and FeSO(4) (before baking) treatment groups
were significant, but the difference between the before and after HR treatment
groups was not significant. We conclude that bread baking does not enhance the
bioavailability of elemental iron powders.
PMID- 17032053
TI - Jug r 4, a legumin group food allergen from walnut (Juglans regia Cv. Chandler).
AB - Allergy to walnut is the most frequently reported tree nut allergy in the United
States. Walnut 2S albumin, a vicilin-like protein, and a lipid transfer protein
allergen have previously been described. Our objective was to clone and express a
cDNA encoding a legumin group protein, assess IgE-binding with sera from walnut
allergic patients, and investigate cross-reactivity with selected nuts. Primers
were used to obtain the cDNA by 5' and 3' rapid amplification of cDNA ends from
walnut mRNA. The cDNA was subcloned into the pMAL-c2X vector and the recombinant
fusion protein, named rJug r 4, was expressed in Escherichia coli. The obtained
cDNA encoded a precursor protein with a predicted molecular weight of 58.1 kD,
which showed significant sequence homology to hazelnut and cashew legumin
allergens. Serum IgE from 21 of 37 (57%) patients bound the rJug r 4 fusion
protein. In vitro cross-reactivity was demonstrated with hazelnut, cashew, and
peanut protein extracts.
PMID- 17032054
TI - Effect of red wine marinades on the formation of heterocyclic amines in fried
chicken breast.
AB - Genotoxic heterocyclic amines (HAs) are formed via the Maillard reaction and free
radical reaction mechanisms when meat or fish is cooked at usual cooking
conditions. In this paper, the effect of the addition of red wine was tested to
study if it interferes in HA formation. Fried chicken breast was the food item
chosen, and three different red wines, characterized in terms of grape varieties,
free amino acids, antioxidant properties, and metallic composition, were used to
marinate meat prior to the heating process. Unmarinated samples and samples
marinated with an ethanol-water mixture provided reference HA levels. The frying
experiments were performed under well-controlled temperature and time conditions.
The samples were analyzed for HA content using solid-phase extraction and LC
MS/MS. DMIP, PhIP, MeIQx, 4,8-DiMeIQx, IFP, TMIP, harman, and norharman were
identified in fried chicken breast. Red wine marinades were found to reduce the
formation of some of the HAs formed. PhIP, with a reduction of up to 88%, was the
most minimized amine, although the formation of harman was enhanced.
PMID- 17032055
TI - Concentrations of perfluorooctanesulfonamides in Canadian total diet study
composite food samples collected between 1992 and 2004.
AB - Canadian Total Diet Study composite samples collected from 1992 to 2004 (n = 151)
were analyzed for a series of perfluorooctanesulfonamides that are likely
breakdown products or manufacturing residuals associated with
perfluorooctylsulfonyl phosphate esters. These esters have been incorporated into
coatings for paper and paperboard used in food packaging. N
Ethylperfluorooctanesulfonamide (N-EtPFOSA), perfluorooctanesulfonamide, N,N
diethylperfluorooctanesulfonamide, N-methylperfluorooctanesulfonamide, and N,N
dimethylperfluorooctanesulfonamide were extracted using solvent extraction and
quantified by gas chromatography-mass spectrometry. Perfluorooctanesulfonamides
were detected in the picograms per gram to low nanograms per gram of wet weight
range in all food groups tested-baked goods and candy, dairy, eggs, fast food,
fish, meat, and foods to be prepared in packaging. The highest concentrations of
total perfluorooctanesulfonamides were observed in fast food composites (from
less than the method detection limit to 27300 pg/g of wet weight). Concentrations
of N-EtPFOSA appeared to decrease over the sampling period (1992-2004) in French
fries and other fast food composites; no such trend was apparent in freshwater
fish, marine fish, and shellfish composites. A basic estimate of dietary exposure
to perfluorooctanesulfonamides suggests that Canadians (>12 years old) are
exposed to approximately 73 ng/person/day from these foods.
PMID- 17032058
TI - Lentiviral gene transfer of RPE65 rescues survival and function of cones in a
mouse model of Leber congenital amaurosis.
AB - BACKGROUND: RPE65 is specifically expressed in the retinal pigment epithelium and
is essential for the recycling of 11-cis-retinal, the chromophore of rod and cone
opsins. In humans, mutations in RPE65 lead to Leber congenital amaurosis or early
onset retinal dystrophy, a severe form of retinitis pigmentosa. The proof of
feasibility of gene therapy for RPE65 deficiency has already been established in
a dog model of Leber congenital amaurosis, but rescue of the cone function,
although crucial for human high-acuity vision, has never been strictly proven. In
Rpe65 knockout mice, photoreceptors show a drastically reduced light sensitivity
and are subject to degeneration, the cone photoreceptors being lost at early
stages of the disease. In the present study, we address the question of whether
application of a lentiviral vector expressing the Rpe65 mouse cDNA prevents cone
degeneration and restores cone function in Rpe65 knockout mice. METHODS AND
FINDINGS: Subretinal injection of the vector in Rpe65-deficient mice led to
sustained expression of Rpe65 in the retinal pigment epithelium.
Electroretinogram recordings showed that Rpe65 gene transfer restored retinal
function to a near-normal pattern. We performed histological analyses using cone
specific markers and demonstrated that Rpe65 gene transfer completely prevented
cone degeneration until at least four months, an age at which almost all cones
have degenerated in the untreated Rpe65-deficient mouse. We established an
algorithm that allows prediction of the cone-rescue area as a function of
transgene expression, which should be a useful tool for future clinical trials.
Finally, in mice deficient for both RPE65 and rod transducin, Rpe65 gene transfer
restored cone function when applied at an early stage of the disease.
CONCLUSIONS: By demonstrating that lentivirus-mediated Rpe65 gene transfer
protects and restores the function of cones in the Rpe65(-/-) mouse, this study
reinforces the therapeutic value of gene therapy for RPE65 deficiencies, suggests
a cone-preserving treatment for the retina, and evaluates a potentially effective
viral vector for this purpose.
PMID- 17032059
TI - Cost-effectiveness study of three antimalarial drug combinations in Tanzania.
AB - BACKGROUND: As a result of rising levels of drug resistance to conventional
monotherapy, the World Health Organization (WHO) and other international
organisations have recommended that malaria endemic countries move to combination
therapy, ideally with artemisinin-based combinations (ACTs). Cost is a major
barrier to deployment. There is little evidence from field trials on the cost
effectiveness of these new combinations. METHODS AND FINDINGS: An economic
evaluation of drug combinations was designed around a randomised effectiveness
trial of combinations recommended by the WHO, used to treat Tanzanian children
with non-severe slide-proven malaria. Drug combinations were: amodiaquine (AQ),
AQ with sulfadoxine-pyrimethamine (AQ+SP), AQ with artesunate (AQ+AS), and
artemether-lumefantrine (AL) in a six-dose regimen. Effectiveness was measured in
terms of resource savings and cases of malaria averted (based on parasitological
failure rates at days 14 and 28). All costs to providers and to patients and
their families were estimated and uncertain variables were subjected to
univariate sensitivity analysis. Incremental analysis comparing each combination
to monotherapy (AQ) revealed that from a societal perspective AL was most cost
effective at day 14. At day 28 the difference between AL and AQ+AS was
negligible; both resulted in a gross savings of approximately US1.70 dollars or a
net saving of US22.40 dollars per case averted. Varying the accuracy of diagnosis
and the subsistence wage rate used to value unpaid work had a significant effect
on the number of cases averted and on programme costs, respectively, but this did
not change the finding that AL and AQ+AS dominate monotherapy. CONCLUSIONS: In an
area of high drug resistance, there is evidence that AL and AQ+AS are the most
cost-effective drugs despite being the most expensive, because they are
significantly more effective than other options and therefore reduce the need for
further treatment. This is not necessarily the case in parts of Africa where
recrudescence following SP and AQ treatment (and their combination) is lower so
that the relative advantage of ACTs is smaller, or where diagnostic services are
not accurate and as a result much of the drug goes to those who do not have
malaria.
PMID- 17032060
TI - A population-based study on alcohol and high-risk sexual behaviors in Botswana.
AB - BACKGROUND: In Botswana, an estimated 24% of adults ages 15-49 years are infected
with HIV. While alcohol use is strongly associated with HIV infection in Africa,
few population-based studies have characterized the association of alcohol use
with specific high-risk sexual behaviors. METHODS AND FINDINGS: We conducted a
cross-sectional, population-based study of 1,268 adults from five districts in
Botswana using a stratified two-stage probability sample design. Multivariate
logistic regression was used to assess correlates of heavy alcohol consumption
(>14 drinks/week for women, and >21 drinks/week for men) as a dependent variable.
We also assessed gender-specific associations between alcohol use as a primary
independent variable (categorized as none, moderate, problem and heavy drinking)
and several risky sex outcomes including: (a) having unprotected sex with a
nonmonogamous partner; (b) having multiple sexual partners; and (c) paying for or
selling sex in exchange for money or other resources. Criteria for heavy drinking
were met by 31% of men and 17% of women. Adjusted correlates of heavy alcohol use
included male gender, intergenerational relationships (age gap > or =10 y),
higher education, and living with a sexual partner. Among men, heavy alcohol use
was associated with higher odds of all risky sex outcomes examined, including
unprotected sex (AOR = 3.48; 95% confidence interval [CI], 1.65 to 7.32),
multiple partners (AOR = 3.08; 95% CI, 1.95 to 4.87), and paying for sex (AOR =
3.65; 95% CI, 2.58 to 12.37). Similarly, among women, heavy alcohol consumption
was associated with higher odds of unprotected sex (AOR = 3.28; 95% CI, 1.71 to
6.28), multiple partners (AOR = 3.05; 95% CI, 1.83 to 5.07), and selling sex (AOR
= 8.50; 95% CI, 3.41 to 21.18). A dose-response relationship was seen between
alcohol use and risky sexual behaviors, with moderate drinkers at lower risk than
both problem and heavy drinkers. CONCLUSIONS: Alcohol use is associated with
multiple risks for HIV transmission among both men and women. The findings of
this study underscore the need to integrate alcohol abuse and HIV prevention
efforts in Botswana and elsewhere.
PMID- 17032061
TI - Responding to AIDS, tuberculosis, malaria, and emerging infectious diseases in
Burma: dilemmas of policy and practice.
PMID- 17032062
TI - HIV-1 viral load assays for resource-limited settings.
PMID- 17032063
TI - Asymmetrical reinforcement and Wolbachia infection in Drosophila.
AB - Reinforcement refers to the evolution of increased mating discrimination against
heterospecific individuals in zones of geographic overlap and can be considered a
final stage in the speciation process. One the factors that may affect
reinforcement is the degree to which hybrid matings result in the permanent loss
of genes from a species' gene pool. Matings between females of Drosophila
subquinaria and males of D. recens result in high levels of offspring mortality,
due to interspecific cytoplasmic incompatibility caused by Wolbachia infection of
D. recens. Such hybrid inviability is not manifested in matings between D. recens
females and D. subquinaria males. Here we ask whether the asymmetrical hybrid
inviability is associated with a corresponding asymmetry in the level of
reinforcement. The geographic ranges of D. recens and D. subquinaria were found
to overlap across a broad belt of boreal forest in central Canada. Females of D.
subquinaria from the zone of sympatry exhibit much stronger levels of
discrimination against males of D. recens than do females from allopatric
populations. In contrast, such reproductive character displacement is not evident
in D. recens, consistent with the expected effects of unidirectional cytoplasmic
incompatibility. Furthermore, there is substantial behavioral isolation within D.
subquinaria, because females from populations sympatric with D. recens
discriminate against allopatric conspecific males, whereas females from
populations allopatric with D. recens show no discrimination against any
conspecific males. Patterns of general genetic differentiation among populations
are not consistent with patterns of behavioral discrimination, which suggests
that the behavioral isolation within D. subquinaria results from selection
against mating with Wolbachia-infected D. recens. Interspecific cytoplasmic
incompatibility may contribute not only to post-mating isolation, an effect
already widely recognized, but also to reinforcement, particularly in the
uninfected species. The resulting reproductive character displacement not only
increases behavioral isolation from the Wolbachia-infected species, but may also
lead to behavioral isolation between populations of the uninfected species. Given
the widespread occurrence of Wolbachia among insects, it thus appears that there
are multiple ways by which these endosymbionts may directly and indirectly
contribute to reproductive isolation and speciation.
PMID- 17032064
TI - CDPKs CPK6 and CPK3 function in ABA regulation of guard cell S-type anion- and
Ca(2+)-permeable channels and stomatal closure.
AB - Abscisic acid (ABA) signal transduction has been proposed to utilize cytosolic
Ca(2+) in guard cell ion channel regulation. However, genetic mutants in Ca(2+)
sensors that impair guard cell or plant ion channel signaling responses have not
been identified, and whether Ca(2+)-independent ABA signaling mechanisms suffice
for a full response remains unclear. Calcium-dependent protein kinases (CDPKs)
have been proposed to contribute to central signal transduction responses in
plants. However, no Arabidopsis CDPK gene disruption mutant phenotype has been
reported to date, likely due to overlapping redundancies in CDPKs. Two
Arabidopsis guard cell-expressed CDPK genes, CPK3 and CPK6, showed gene
disruption phenotypes. ABA and Ca(2+) activation of slow-type anion channels and,
interestingly, ABA activation of plasma membrane Ca(2+)-permeable channels were
impaired in independent alleles of single and double cpk3cpk6 mutant guard cells.
Furthermore, ABA- and Ca(2+)-induced stomatal closing were partially impaired in
these cpk3cpk6 mutant alleles. However, rapid-type anion channel current activity
was not affected, consistent with the partial stomatal closing response in double
mutants via a proposed branched signaling network. Imposed Ca(2+) oscillation
experiments revealed that Ca(2+)-reactive stomatal closure was reduced in CDPK
double mutant plants. However, long-lasting Ca(2+)-programmed stomatal closure
was not impaired, providing genetic evidence for a functional separation of these
two modes of Ca(2+)-induced stomatal closing. Our findings show important
functions of the CPK6 and CPK3 CDPKs in guard cell ion channel regulation and
provide genetic evidence for calcium sensors that transduce stomatal ABA
signaling.
PMID- 17032065
TI - Strict host-symbiont cospeciation and reductive genome evolution in insect gut
bacteria.
AB - Host-symbiont cospeciation and reductive genome evolution have been identified in
obligate endocellular insect symbionts, but no such example has been identified
from extracellular ones. Here we first report such a case in stinkbugs of the
family Plataspidae, wherein a specific gut bacterium is vertically transmitted
via "symbiont capsule." In all of the plataspid species, females produced
symbiont capsules upon oviposition and their gut exhibited specialized traits for
capsule production. Phylogenetic analysis showed that the plataspid symbionts
constituted a distinct group in the gamma-Proteobacteria, whose sister group was
the aphid obligate endocellular symbionts Buchnera. Removal of the symbionts
resulted in retarded growth, mortality, and sterility of the insects. The host
phylogeny perfectly agreed with the symbiont phylogeny, indicating strict host
symbiont cospeciation despite the extracellular association. The symbionts
exhibited AT-biased nucleotide composition, accelerated molecular evolution, and
reduced genome size, as has been observed in obligate endocellular insect
symbionts. These findings suggest that not the endocellular conditions themselves
but the population genetic attributes of the vertically transmitted symbionts are
probably responsible for the peculiar genetic traits of these insect symbionts.
We proposed the designation "Candidatus Ishikawaella capsulata" for the plataspid
symbionts. The plataspid stinkbugs, wherein the host-symbiont associations can be
easily manipulated, provide a novel system that enables experimental approaches
to previously untouched aspects of the insect-microbe mutualism. Furthermore,
comparative analyses of the sister groups, the endocellular Buchnera and the
extracellular Ishikawaella, would lead to insights into how the different
symbiotic lifestyles have affected their genomic evolution.
PMID- 17032066
TI - A signaling network for patterning of neuronal connectivity in the Drosophila
brain.
AB - The precise number and pattern of axonal connections generated during brain
development regulates animal behavior. Therefore, understanding how developmental
signals interact to regulate axonal extension and retraction to achieve precise
neuronal connectivity is a fundamental goal of neurobiology. We investigated this
question in the developing adult brain of Drosophila and find that it is
regulated by crosstalk between Wnt, fibroblast growth factor (FGF) receptor, and
Jun N-terminal kinase (JNK) signaling, but independent of neuronal activity. The
Rac1 GTPase integrates a Wnt-Frizzled-Disheveled axon-stabilizing signal and a
Branchless (FGF)-Breathless (FGF receptor) axon-retracting signal to modulate JNK
activity. JNK activity is necessary and sufficient for axon extension, whereas
the antagonistic Wnt and FGF signals act to balance the extension and retraction
required for the generation of the precise wiring pattern.
PMID- 17032067
TI - The end of the end of ideology.
AB - The "end of ideology" was declared by social scientists in the aftermath of World
War II. They argued that (a) ordinary citizens' political attitudes lack the kind
of stability, consistency, and constraint that ideology requires; (b) ideological
constructs such as liberalism and conservatism lack motivational potency and
behavioral significance; (c) there are no major differences in content (or
substance) between liberal and conservative points of view; and (d) there are few
important differences in psychological processes (or styles) that underlie
liberal versus conservative orientations. The end-of-ideologists were so
influential that researchers ignored the topic of ideology for many years.
However, current political realities, recent data from the American National
Election Studies, and results from an emerging psychological paradigm provide
strong grounds for returning to the study of ideology. Studies reveal that there
are indeed meaningful political and psychological differences that covary with
ideological self-placement. Situational variables--including system threat and
mortality salience--and dispositional variables--including openness and
conscientiousness--affect the degree to which an individual is drawn to liberal
versus conservative leaders, parties, and opinions. A psychological analysis is
also useful for understanding the political divide between "red states" and "blue
states."
PMID- 17032068
TI - Evidence-based youth psychotherapies versus usual clinical care: a meta-analysis
of direct comparisons.
AB - In the debate over evidence-based treatments (EBTs) for youth, one question is
central: Do EBTs produce better outcomes than the usual interventions employed in
clinical care? The authors addressed this question through a meta-analysis of 32
randomized trials that directly compared EBTs with usual care. EBTs outperformed
usual care. Effects fell within the small to medium range at posttreatment,
increasing somewhat at follow-up. EBT superiority was not reduced by high levels
of youth severity or by inclusion of minority youths. The findings underscore a
need for improved study designs and detailed treatment descriptions. In the
future, the EBT versus usual care genre can inform the search for the most
effective interventions and guide treatment selection in clinical care.
PMID- 17032069
TI - Mental balance and well-being: building bridges between Buddhism and Western
psychology.
AB - Clinical psychology has focused primarily on the diagnosis and treatment of
mental disease, and only recently has scientific attention turned to
understanding and cultivating positive mental health. The Buddhist tradition, on
the other hand, has focused for over 2,500 years on cultivating exceptional
states of mental well-being as well as identifying and treating psychological
problems. This article attempts to draw on centuries of Buddhist experiential and
theoretical inquiry as well as current Western experimental research to highlight
specific themes that are particularly relevant to exploring the nature of mental
health. Specifically, the authors discuss the nature of mental well-being and
then present an innovative model of how to attain such well-being through the
cultivation of four types of mental balance: conative, attentional, cognitive,
and affective.
PMID- 17032070
TI - The psychotherapy adaptation and modification framework: application to Asian
Americans.
AB - Although effective treatments for many mental disorders have been developed,
little research has been conducted to determine whether these interventions are
effective in treating those from diverse backgrounds. Recent reports have
suggested that ethnic minorities are less likely to receive quality health
services and that they evidence worse treatment outcomes when compared with other
groups. To improve care for those from diverse backgrounds, Western-developed
psychotherapies may need to be culturally modified or adapted to become more
effective in treating ethnic minorities. This article addresses the need for
adapting psychotherapy and provides a conceptual framework for making such
modifications. The psychotherapy adaptation and modification framework model is
applied to recent Asian American immigrants as an illustrative example. However,
it may also serve as a point of departure to adapt therapies for other
ethnocultural groups.
PMID- 17032078
TI - Cognitive sex differences and mathematics and science achievement.
PMID- 17032079
TI - There is more to aptitude than cognitive capacities.
PMID- 17032080
TI - Cognitive styles partly explain gender disparity in engineering.
PMID- 17032083
TI - On the cover.
PMID- 17032082
TI - The poor availability of psychological research data for reanalysis.
PMID- 17032084
TI - Introduction to the special section: growth following highly stressful life
events--current status and future directions.
AB - Interest in the phenomenon of perceived growth following highly stressful
experiences continues to proliferate. Already there is abundant evidence that
perceptions of growth are commonly reported, often by the majority of people
experiencing even the most traumatic of events. However, much remains to be
learned about perceptions of growth. In this article, the authors pose 7 major
theoretical and empirical questions regarding perceived growth, including issues
of measurement, validity, mechanisms, links with well-being, and clinical
implications. The authors summarize the current status of psychologists'
knowledge, including articles in the present special section, and conclude that
there is much to learn about perceived growth. The authors end with suggestions
for future research.
PMID- 17032085
TI - A meta-analytic review of benefit finding and growth.
AB - The authors conducted a meta-analysis to examine the relations of benefit finding
to psychological and physical health as well as to a specific set of demographic,
stressor, personality, and coping correlates. Results from 87 cross-sectional
studies reported in 77 articles showed that benefit finding was related to less
depression and more positive well-being but also more intrusive and avoidant
thoughts about the stressor. Benefit finding was unrelated to anxiety, global
distress, quality of life, and subjective reports of physical health. Moderator
analyses showed that relations of benefit finding to outcomes were affected by
the amount of time that had passed since stressor onset, the benefit finding
measured used, and the racial composition of the sample.
PMID- 17032086
TI - Posttraumatic growth and HIV disease progression.
AB - The relationship between posttraumatic growth (PTG; perceiving positive changes
since diagnosis) and disease status, determined by changes in viral load and CD4
count over time, was examined among 412 people living with HIV. In controlled
multiple regression models, PTG was not associated with disease status over time
for the entire sample. However, there were significant associations for certain
subgroups. PTG was positively associated with CD4 counts for Hispanic
participants (vs. non-Hispanic) and those with low (vs. high) levels of optimism.
PTG was inversely associated with viral load among those low (vs. high) in
pessimism. Although PTG was inversely associated with depressive symptoms,
alcohol, and illicit drug use, these factors did not account for the findings.
PMID- 17032087
TI - Curvilinear associations between benefit finding and psychosocial adjustment to
breast cancer.
AB - Two previously studied cohorts of women with nonmetastatic breast cancer (Ns =
230 and 136) were reexamined. Participants were assessed during the year after
surgery and 5-8 years later. Associations were examined between benefit finding
(BF) and several indicators of psychosocial adjustment (e.g., perceived quality
of life, positive affect, negative affect, social disruption, and intrusive
thoughts). Significant curvilinear relations between BF and other outcomes were
observed cross-sectionally during initial assessment and at long-term follow-up
in both samples. Compared with the intermediate BF group, low and high BF groups
had better psychosocial adjustment. Further analyses indicated that the high BF
group reported higher optimism and more use of positive reframing and religious
coping than the other BF groups. Discussion highlights the need to examine
nonlinear as well as linear relationships.
PMID- 17032088
TI - Urban teens: Trauma, posttraumatic growth, and emotional distress among female
adolescents.
AB - Urban teens face many traumas, with implications for potential growth and
distress. This study examined traumatic events, posttraumatic growth, and
emotional distress over 18 months among urban adolescent girls (N = 328).
Objectives were to (a) describe types of traumatic events, (b) determine how type
and timing of events relate to profiles of posttraumatic growth, and (c)
prospectively examine effects of event type and posttraumatic growth on short-
and long-term emotional distress with controls for pre-event distress. Results
indicate that type of event was related to profiles of posttraumatic growth, but
not with subsequent emotional distress. When baseline emotional distress was
controlled, posttraumatic growth was associated with subsequent reductions in
short- and long-term emotional distress. Implications for future research and
clinical practice with adolescents are addressed.
PMID- 17032089
TI - The assessment and validity of stress-related growth in a community-based sample.
AB - In an investigation of the assessment and construct validity of stress-related
growth, community-dwelling women (N = 163) wrote essays about the impact of a
stressful life event that had occurred in the previous few years and completed
the Posttraumatic Growth Inventory (PTGI). Independent ratings of growth in the
essays were positively correlated with PTGI scores, suggesting that endorsement
of growth on questionnaires can be substantiated by personal accounts. There was
no relation between reports of growth on the PTGI and socially desirable
responding or negative mood. Higher PTGI scores were associated with greater
positive mood and greater depth of processing in the essays. These findings
support the validity of stress-related growth as a construct and its assessment
via questionnaire.
PMID- 17032090
TI - Assessing the validity of self-reported stress-related growth.
AB - The purpose of these studies was to assess the validity of self-reported stress
related growth (SRG). In Study 1, individuals with breast cancer (n = 70)
generally did not report greater well-being than a matched comparison group (n =
70). In Study 2, there were no significant differences in well-being between
undergraduate students who said that something positive had come out of their
worst stressor (n = 34) and those who reported no positives (n = 34). In Study 3,
specific domains of SRG assessed in undergraduate students (n = 96) generally
were not uniquely related to corresponding well-being measures. Thus, the authors
found fairly little evidence for the validity of self-reported SRG. Future
research directions are highlighted.
PMID- 17032091
TI - Perception of benefits and costs during SARS outbreak: An 18-month prospective
study.
AB - In this study, the authors examined perceived benefits and costs of the outbreak
of severe acute respiratory syndrome (SARS). Mixed accounts of benefits and
costs, rather than exclusive accounts of only benefits or costs, were proposed to
be characterized by nondefensiveness and enduring changes in psychosocial
resources. Participants were 70 SARS recoverers, 59 family members of SARS
recoverers, and 172 healthy adults residing in Hong Kong--a SARS-affected region.
Results show that participants giving an exclusive account of benefits had higher
levels of defensiveness than those giving a mixed account and those giving an
exclusive account of costs. Only the perceived impact of benefits given in mixed
accounts were related to future accruements in personal and social resources over
an 18-month period.
PMID- 17032092
TI - Neural correlates of posttraumatic growth after severe motor vehicle accidents.
AB - Frontal brain asymmetry has been associated with emotion- and motivation-related
constructs. The authors examined the relationship between frontal brain asymmetry
and subjective perception of posttraumatic growth (PTG) after severe motor
vehicle accidents (MVAs). Eighty-two survivors of MVAs completed self-report
measures of PTG, trait and state affect, and diagnostic interviews assessing
clinical status, and underwent measurement of resting electroencephalographic
activity. As predicted, increased relative left frontal activation was
significantly related to PTG, even when statistically controlling for
dispositional positive affect. The authors assume that approach-related
motivational tendencies associated with higher relative left frontal brain
activity may be involved in the process and outcome of PTG.
PMID- 17032093
TI - Writing about the benefits of an interpersonal transgression facilitates
forgiveness.
AB - The authors examined the effects of writing about the benefits of an
interpersonal transgression on forgiveness. Participants (N = 304) were randomly
assigned to one of three 20-min writing tasks in which they wrote about either
(a) traumatic features of the most recent interpersonal transgression they had
suffered, (b) personal benefits resulting from the transgression, or (c) a
control topic that was unrelated to the transgression. Participants in the
benefit-finding condition became more forgiving toward their transgressors than
did those in the other 2 conditions, who did not differ from each other. In part,
the benefit-finding condition appeared to facilitate forgiveness by encouraging
participants to engage in cognitive processing as they wrote their essays.
Results suggest that benefit finding may be a unique and useful addition to
efforts to help people forgive interpersonal transgressions through structured
interventions. The Transgression-Related Interpersonal Motivations Inventory--18
Item Version (TRIM-18) is appended.
PMID- 17032094
TI - Cognitive processing therapy for veterans with military-related posttraumatic
stress disorder.
AB - Sixty veterans (54 men, 6 women) with chronic military-related posttraumatic
stress disorder (PTSD) participated in a wait-list controlled trial of cognitive
processing therapy (CPT). The overall dropout rate was 16.6% (20% from CPT, 13%
from waiting list). Random regression analyses of the intention-to-treat sample
revealed significant improvements in PTSD and comorbid symptoms in the CPT
condition compared with the wait-list condition. Forty percent of the intention
to-treat sample receiving CPT did not meet criteria for a PTSD diagnosis, and 50%
had a reliable change in their PTSD symptoms at posttreatment assessment. There
was no relationship between PTSD disability status and outcomes. This trial
provides some of the most encouraging results of PTSD treatment for veterans with
chronic PTSD and supports increased use of cognitive- behavioral treatments in
this population.
PMID- 17032095
TI - Benzodiazepine discontinuation among adults with GAD: A randomized trial of
cognitive-behavioral therapy.
AB - This study evaluated the specific effectiveness of cognitive-behavior therapy
(CBT) combined with medication tapering for benzodiazepine discontinuation among
generalized anxiety disorder (GAD) patients by using a nonspecific therapy
control group. Sixty-one patients who had used benzodiazepines for more than 12
months were randomly assigned to the experimental conditions. Nearly 75% of
patients in the CBT condition completely ceased benzodiazepine intake, as
compared with 37% in the control condition. Results of the 3-, 6-, and 12-month
follow-ups confirmed the maintenance of complete cessation. Discontinuation rates
remained twice as high in the CBT condition. The number of patients who no longer
met GAD criteria was also greater in the CBT condition. The addition of specific
CBT components thus seemed to facilitate benzodiazepine tapering among patients
with GAD.
PMID- 17032096
TI - The effects of forgiveness therapy on depression, anxiety, and posttraumatic
stress for women after spousal emotional abuse.
AB - Emotionally abused women experience negative psychological outcomes long after
the abusive spousal relationship has ended. This study compares forgiveness
therapy (FT) with an alternative treatment (AT; anger validation, assertiveness,
interpersonal skill building) for emotionally abused women who had been
permanently separated for 2 or more years (M = 5.00 years, SD = 2.61; n = 10 per
group). Participants, who were matched, yoked, and randomized to treatment group,
met individually with the intervener. Mean intervention time was 7.95 months (SD
= 2.61). The relative efficacy of FT and AT was assessed at p < .05. Participants
in FT experienced significantly greater improvement than AT participants in
depression, trait anxiety, posttraumatic stress symptoms, self-esteem,
forgiveness, environmental mastery, and finding meaning in suffering, with gains
maintained at follow-up (M = 8.35 months, SD = 1.53). FT has implications for the
long-term recovery of postrelationship emotionally abused women.
PMID- 17032097
TI - The relationship of perfectionism, depression, and therapeutic alliance during
treatment for depression: latent difference score analysis.
AB - The authors examined the longitudinal relationship of patient-rated
perfectionism, clinician-rated depression, and observer-rated therapeutic
alliance using the latent difference score (LDS) analytic framework. Outpatients
involved in the Treatment for Depression Collaborative Research Program completed
measures of perfectionism and depression at 5 occasions throughout treatment,
with therapeutic alliance measured early in therapy. First, LDS analyses of
perfectionism and depression established longitudinal change models. Further LDS
analyses revealed significant longitudinal interrelationships, in which
perfectionism predicted the subsequent rate of depression change, consistent with
a personality vulnerability model of depression. In the final LDS model, the
strength of the therapeutic alliance significantly predicted longitudinal
perfectionism change, and perfectionism significantly predicted the rate of
depression change throughout therapy. These results clarify the patterns of
growth and change for these indicators throughout depression treatment,
demonstrating an alternative method for evaluating longitudinal dynamics in
therapy.
PMID- 17032098
TI - Brief motivational interventions for heavy college drinkers: A randomized
controlled trial.
AB - In this randomized controlled trial, the authors evaluated brief motivational
interventions (BMIs) for at-risk college drinkers. Heavy drinking students (N =
509; 65% women, 35% men) were randomized into 1 of 6 intervention conditions
formed by crossing the baseline Timeline Followback (TLFB) interview (present
versus absent) and intervention type (basic BMI, BMI enhanced with a decisional
balance module, or none). Assessments completed at baseline, 1, 6, and 12 months
measured typical and risky drinking as well as drinking-related problems.
Relative to controls, the TLFB interview reduced consumption but not problems at
1 month. The basic BMI improved all drinking outcomes beyond the effects of the
TLFB interview at 1 month, whereas the enhanced BMI did not. Risk reduction
achieved by brief interventions maintained throughout the follow-up year.
PMID- 17032100
TI - Psychiatric symptoms and community violence among high-risk patients: A test of
the relationship at the weekly level.
AB - Given the availability of violence risk assessment tools, clinicians are now
better able to identify high-risk patients. Once these patients have been
identified, clinicians must monitor risk state and intervene when necessary to
prevent harm. Clinical practice is dominated by the assumption that increases in
psychiatric symptoms elevate risk of imminent violence. This intensive study of
patients (N = 132) at high risk for community violence is the first to evaluate
prospectively the temporal relation between symptoms and violence. Symptoms were
assessed with the Brief Symptom Inventory and threat/control override (TCO)
scales. Results indicate that a high-risk patient with increased anger in 1 week
is significantly more likely to be involved in serious violence in the following
week. This was not true of other symptom constellations (anxiety, depression,
TCO) or general psychological distress. The authors found no evidence that
increases in the latter symptoms during 1 week provide an independent foundation
for expecting violence during the following week.
PMID- 17032099
TI - The use of contingency management and motivational/skills-building therapy to
treat young adults with marijuana dependence.
AB - Marijuana-dependent young adults (N = 136), all referred by the criminal justice
system, were randomized to 1 of 4 treatment conditions: a motivational/skills
building intervention (motivational enhancement therapy/cognitive-behavioral
therapy; MET/CBT) plus incentives contingent on session attendance or submission
of marijuana-free urine specimens (contingency management; CM), MET/CBT without
CM, individual drug counseling (DC) plus CM, and DC without CM. There was a
significant main effect of CM on treatment retention and marijuana-free urine
specimens. Moreover, the combination of MET/CBT plus CM was significantly more
effective than MET/CBT without CM or DC plus CM, which were in turn more
effective than DC without CM for treatment attendance and percentage of marijuana
free urine specimens. Participants assigned to MET/CBT continued to reduce the
frequency of their marijuana use through a 6-month follow-up.
PMID- 17032101
TI - Cognitive adaptation theory and breast cancer recurrence: Are there limits?
AB - Relations of the components of cognitive adaptation theory (self-esteem,
optimism, control) to quality of life and benefit finding were examined for 70
women (91% Caucasian) diagnosed with Stage I, II, or III breast cancer over 5
years ago. Half of these women experienced a recurrence within the 5 years; the
other half remained disease free. Women were matched on age, race, stage of
disease, and intervention condition. Baseline perceptions of personal control
over illness, but not general self-esteem or optimism, were associated with
women's reports of worse physical functioning, worse mental functioning, and less
benefit finding 5 years later for recurrent women but not disease-free women.
These findings highlight the notion that there may be boundary conditions on the
adaptiveness of perceived control.
PMID- 17032102
TI - Temporary anchorage devices for tooth movement: a review and case reports.
AB - BACKGROUND: Temporary anchorage devices (TADs) are immediately loaded miniscrews
and osseointegrated palatal implants that are placed to control tooth movement
during orthodontic treatment and removed when the treatment is completed. They
are a relatively new addition to the dental armamentarium and can be used in some
cases to replace traditional orthodontic extraoral appliances. Because placement
requires a surgical procedure, orthodontists often refer patients to
periodontists for this stage of the overall treatment plan. METHODS: The purpose
of this article is to introduce TADs to the periodontal community by reviewing
their purpose, various systems that are available, indications for use, site
selection, and surgical technique. Case reports are included to illustrate this
new treatment approach. RESULTS: Placement of osseointegrated implants for
restorative purposes is an established procedure in most periodontal offices.
Although placement of TADs is a modification of these familiar techniques, most
of these devices serve a very different purpose, involving new loading protocols
with no expectation of osseointegration in patients usually not receiving
concomitant periodontal therapy. CONCLUSIONS: Periodontists' knowledge of soft
and hard tissue anatomy and their ability to manage soft tissue position them
well to collaborate with orthodontists in this multidisciplinary treatment.
However, as with every new modality, clinicians need to understand the specific
uses and limitations of TADs and work closely with their referring orthodontists
in identifying patients for whom miniscrew implants are a viable option.
Periodontal practices are based primarily on referrals from dental colleagues,
and the concept of periodontists working cooperatively with orthodontists is not
new. Including TAD placement among the services periodontists offer provides
another opportunity to further this relationship and to establish periodontists
as appropriate resources for this segment of orthodontic treatment.
PMID- 17032103
TI - Flap thickness as a predictor of root coverage: a systematic review.
AB - BACKGROUND: Thick gingival tissue eases manipulation, maintains vascularity, and
promotes wound healing during and after surgery. A few recent case reports
correlate greater flap thickness to mean and complete root coverage after
mucogingival therapy for recession defects. The aim of this systematic review is
to appraise the current literature on this subject and to combine existing data
to verify the presence of any association between gingival thickness and root
coverage outcomes. METHODS: Human studies that reported the number and class of
recessions, measured flap thickness at a well-defined location, described the
method of root coverage used, followed results for at least 3 months, and
detailed mean root coverage underwent review and statistical analysis.
Investigations were scored from 1 to 5 based on methodological quality. Weighted
gingival thickness and weighted mean root coverage was calculated based on
standard error. Statistical analysis used the Mann-Whitney test, analysis of
variance (ANOVA), and linear regression to determine any correlation between a
number of factors (i.e., thickness, treatment type, and follow-up time) and mean
and complete root coverage. A significant P value was set at <0.05. RESULTS:
Fifteen investigations met the inclusion criteria. All of these reported at least
0.7 mm of flap thickness, although measurement locations varied. Treatment
modalities included coronally advanced flap, connective tissue graft, and guided
tissue regeneration with and without adjuncts. A significant moderate correlation
occurred between weighted flap thickness and weighted mean root coverage and
weighted complete root coverage (r = 0.646 and 0.454, respectively). According to
Mann-Whitney analysis, a critical threshold thickness >1.1 mm existed for
weighted mean and complete root coverage (P <0.02). The type of treatment
rendered also influenced root coverage. Further simple linear regression revealed
a high correlation between weighted thickness and weighted mean root coverage in
connective tissue grafting and guided tissue regeneration (r = 0.909 and 0.714,
respectively) but not coronally advanced flap therapy. Study score and follow-up
time did not affect the percentage of root coverage. CONCLUSION: Within the
limits of this review, a positive association exists between weighted flap
thickness and mean and complete root coverage.
PMID- 17032104
TI - Effect of periodontal treatment on serum C-reactive protein levels: a systematic
review and meta-analysis.
AB - BACKGROUND: Systemic inflammation is increasingly being recognized as a risk
factor for adverse cardiovascular events. Evidence is accumulating that
associates periodontal disease with a higher risk for atherosclerotic plaque
formation. A positive association between circulating C-reactive protein (CRP)
levels and periodontal disease may be responsible for these observations. We
undertook a systematic review and conducted a meta-analysis of the available
evidence to examine the effect of periodontal treatment on systemic CRP levels
and to assess the quality of the available evidence. METHODS: We conducted a
systematic search of the English-language literature on the effect of periodontal
treatment on CRP levels, as assessed by high-sensitivity assays, at least 2
months after periodontal treatment. The search was conducted in MEDLINE between
1966 and July 2005 and the Cochrane Central Register of Controlled Trials. We
performed a meta-analysis using the DerSimonian and Laird random-effects model.
RESULTS: The literature search yielded 814 citations of which 10 met the
inclusion criteria. The meta-analysis of the randomized controlled trials (RCTs)
showed that the difference in serum CRP levels is not significantly different
between the two arms. Similarly, results from the single-cohort studies showed
that the difference on serum CRP levels was not significantly different before
and after treatment. CONCLUSIONS: There is now a large body of evidence to
indicate that systemic inflammation is present in patients with periodontal
disease. Thus, information from RCTs and single-cohort studies does not support
the hypothesis that periodontal treatment can reduce systemic CRP levels.
PMID- 17032105
TI - Gingivitis and periodontitis as antagonistic modulators of gingival perfusion.
AB - BACKGROUND: We explore the possible association between the extent of gingivitis
or periodontitis and an index of gingival microvascular perfusion response to
compression of alveolar mucosa, called the gingival perfusion index (GIPI).
METHODS: A cross-sectional analytical study was done in a sample of 60 adults,
including healthy and non-insulin-dependent diabetic subjects of either gender,
with teeth in the anteromandibular sextant with or without gingivitis and with or
without periodontitis at the lower-left lateral incisor (LLLI). A sample was
selected by convenience non-probability sampling. Gingival perfusion was
evaluated at labial LLLI attached gingiva. Two perfusion recordings were done 5
minutes apart, each one consisting of a 40-second control phase, a 22-second
compression phase, and a 40-second postcompression phase. LLLI alveolar mucosa
was compressed with a wood-mounted cotton swab until reaching about one-fifth of
the control perfusion value. GIPI was used as response dependent variable. The
gingival index and probing depth were used as measures of the extent of
gingivitis and periodontitis, respectively. RESULTS: By analysis of covariance
and multiple regression analysis, it was found that only the probing depth
(negatively) and gingival index (positively) predicted GIPI (R(2) adjusted =
0.5194, P <0.0001). CONCLUSIONS: The data strongly suggest that, at least in the
studied sample, gingivitis and periodontitis operate as antagonistic modulators
of gingival perfusion. The major practical implication of our findings is that an
increase or decrease in this index (GIPI) at a given attached gingiva site could
indicate, respectively, the clinical predominance of gingivitis or periodontitis
in such a site.
PMID- 17032106
TI - The effects of interproximal distance between roots on the existence of
interdental papillae according to the distance from the contact point to the
alveolar crest.
AB - BACKGROUND: This study investigated the existence of interdental papillae at
certain distances from the contact point to the alveolar crest, depending on the
interproximal distance between roots. METHODS: A total of 206 papillae from 80
patients were examined after the inflammation of the papillae had been minimized
using non-surgical periodontal therapy. The existence of the interdental papillae
was determined using the following categorization: 1) papillae were deemed to be
absent if they did not extend all the way up to the contact point between the
teeth; and 2) papillae were determined to be present if they filled up to the
entire proximal space. The interproximal distance between roots and the distance
from the contact point to the alveolar crest were measured when a full-thickness
flap was used. The number of papillae present interproximally between roots,
according to the distance from the contact point to the alveolar crest, was
analyzed using the x2 analysis method, and the linear-by-linear association
analysis method was used for trend analysis. RESULTS: The number of papillae that
filled the interproximal space decreased with increasing distance from the
contact point to the alveolar crest (P <0.05). In addition, the number of
papillae that filled the interproximal space decreased with increasing
interproximal distance between roots (P <0.05) and became more prominently
decreasing with the increasing distance from the contact point to the alveolar
crest (especially 4, 5, and 6 mm) (P <0.05). CONCLUSION: The results suggest that
the interproximal distance between roots and the distance between the contact
point and the alveolar crest have an independent and combined effect on the
existence of interproximal papillae.
PMID- 17032107
TI - Experimental intrabony and periodontal defects treated with natural mineral
combined with a synthetic cell-binding Peptide in the canine: morphometric
evaluations.
AB - BACKGROUND: A synthetic peptide (P-15) analog of collagen added to anorganic
bovine bone mineral (ABM) has recently been used as an enhanced bone graft
material (ABM/P-15). The objective of this study was to test the contribution of
ABM/P-15 in a new putty form (PEP) in two experimental membrane-protected
defects: periodontal and intrabony. Its efficacy as filler biomaterial in guided
tissue regeneration (GTR) and guided bone regeneration (GBR) procedures was
evaluated histologically and morphometrically. METHODS: In the maxillary canines,
a facial mucoperiosteal flap was raised bilaterally in nine dogs. Two circular
defects, 5 mm in diameter and 2 mm in depth, were made on each side: a
fenestrated periodontal on the canine root and an intrabony in the alveolar
diastema, anteriorly. PEP particles filled both defects on one side; the
contralateral side was blood filled (control). All surgical sites were covered
with a bioabsorbable membrane. Histologically, at 4 months, tissue blocks were
made using the cutting/grinding non-decalcification method followed by
morphometric analysis. In the periodontal fenestration root surface, the linear
percentage of new cementum (%CEM), area percentage of new bone (%NB), and
residual biomaterial particles (%PEP) were calculated. These same measurements
were calculated at the intrabony sites, except cementum. The amount of direct NB
to PEP contact was measured to assess the osteoconductivity level (OSC). The
Pearson correlation test was used to evaluate any significant relationship
between the different measured parameters. RESULTS: In the grafted and non
grafted fenestration root surface defects, %CEM averaged 59.5% and 73.9% (P
<0.02), respectively; %NB averaged 36.1% and 31.4%, respectively; and %PEP
averaged 20.6%. The mean percentage of OSC was 52.4%. In the intrabony grafted
and non-grafted sites, %NB averaged 50.7% and 60.1%, respectively (P <0.02).
Residual %PEP averaged 26.1%, and OSC averaged 35.6%. At the intrabony sites,
higher %NB and lower %OSC were found compared to the fenestration sites (P <0.001
and P <0.03, respectively). Correlation analysis showed a negative correlation
between %NB and %PEP at the fenestration defects. In between the two defect
types, %OSC was significantly correlated (P <0.05). CONCLUSIONS: ABM/P-15 putty
showed osteoconductive and biocompatible qualities. However, at 4 months in this
model, no enhanced regeneration was present compared to a higher CEM and NB
growth detected at non-grafted membrane-protected sites.
PMID- 17032108
TI - Immunohistochemical study of bone sialoprotein and osteopontin in healthy and
diseased root surfaces.
AB - BACKGROUND: Periodontal disease is marked by inflammation and damage to tooth
supporting tissues. In particular, damage occurs to factors present in cementum
that are thought to have the ability to influence the regeneration of surrounding
tissues. Bone sialoprotein and osteopontin are major non-collagenous proteins in
mineralized connective tissues associated with precementoblast chemo-attraction,
adhesion to the root surface, and cell differentiation. The purpose of this
investigation was to determine whether the expression and distribution of bone
sialoprotein and osteopontin on root surfaces affected by periodontitis are
altered compared to healthy, non-diseased root surfaces. METHODS: Thirty healthy
and 30 periodontitis-affected teeth were collected. Following fixation and
demineralization, specimens were embedded in paraffin, sectioned, and exposed to
antibodies against bone sialoprotein and osteopontin. Stained sections were
assessed using light microscopy. RESULTS: Bone sialoprotein was not detected in
the exposed cementum (absence of overlying periodontal ligament) of diseased
teeth. In most areas where the periodontal ligament was intact, bone sialoprotein
was detected for healthy and diseased teeth. For teeth reactive for bone
sialoprotein, the matrix of the cementum just below the periodontal ligament was
moderately stained. A similar immunoreactivity pattern for osteopontin was
observed. CONCLUSIONS: The absence of bone sialoprotein and osteopontin staining
along exposed cementum surfaces may be due to structural and compositional
changes in matrix components associated with periodontal disease. This may
influence the ability for regeneration and new connective tissue attachment onto
previously diseased root surfaces.
PMID- 17032109
TI - Gingival crevicular fluid osteopontin levels in periodontal health and disease.
AB - BACKGROUND: Osteopontin (OPN), a glycosylated phosphoprotein, is a bone matrix
component produced by osteoblasts, osteoclasts, and macrophages as a
multifunctional cytokine. OPN anchors osteoclasts to the bone surface, and its
absence leads to impaired bone resorption. The aim of the present study was to
assess the relation between clinical parameters and concentrations of OPN within
gingival crevicular fluid (GCF) from inflamed gingiva and periodontitis sites
and, subsequently, after the treatment of periodontitis sites. METHODS: A total
of 45 subjects were divided into the following three groups based on modified
gingival index (MGI) and Ramfjord periodontal disease index (PDI) scores: healthy
(group I), gingivitis (group II), and chronic periodontitis (group III). A fourth
group consisted of 15 subjects from group III, 6 to 8 weeks after treatment
(i.e., scaling and root planing [SRP]). GCF samples collected from each patient
were quantified for OPN using the enzymatic immunometric assay. Further, the
correlation between OPN levels in situ with clinical parameters was analyzed in
all groups and before and after treatment in periodontitis patients. RESULTS: The
highest mean OPN concentration in GCF (14.347 microg/ml) was observed in group
III, and the lowest mean OPN concentration in GCF (2.522 microg/ml) was observed
in group I. Its levels in group III decreased to 8.419 microg/ml after treatment
(group IV). Further, GCF OPN levels in all the groups showed a statistically
significant positive correlation with clinical attachment loss (P <0.05).
CONCLUSIONS: OPN levels increase in GCF from healthy to periodontitis states, and
periodontal treatment results in the reduction of OPN levels. The data indicate
that OPN may play a key role in, and could be considered a biomarker of,
periodontal disease progression.
PMID- 17032110
TI - Lack of association between periodontal parameters and preeclampsia.
AB - BACKGROUND: It was hypothesized that periodontal diseases may increase the risk
of preeclampsia. To test this hypothesis, this study was conducted to determine
the association between periodontal parameters and preeclampsia among women in
the north of Jordan. METHODS: A case-control study was conducted among women who
gave birth at Princes Badea Teaching Hospital between September 2004 and May
2005. A total of 115 preeclamptic women and 230 randomly selected controls were
analyzed. The number of teeth, restorations, decayed tooth surfaces, and clinical
periodontal parameters were determined within 24 hours after delivery.
Information regarding participants' demographics, antenatal history, and family
history were collected through personal interviews. RESULTS: After adjustment for
potential confounding factors, there were no statistical differences between
preeclamptic cases and normotensive controls with regard to mean periodontal
probing depth, mean clinical attachment loss, mean gingival recession, mean
plaque index, and mean gingival index. In addition, there were no significant
differences in the percentages of sites with periodontal probing depth >/=3 or
>/=4 mm, percentages of sites with clinical attachment loss >/=3 mm, number of
filled surfaces, and number of missing teeth. Only the number of decayed surfaces
was found to be associated with increased odds of preeclampsia (adjusted odds
ratio of 1.13; 95% confidence interval of 1.02 and 1.25). CONCLUSION: This study
did not support the hypothesis of an association between periodontal parameters
and preeclampsia.
PMID- 17032111
TI - Porcine enamel protein fractions contain transforming growth factor-beta1.
AB - BACKGROUND: Enamel extracts are biologically active and capable of inducing
osteogenesis and cementogenesis, but the specific molecules carrying these
activities have not been ascertained. The purpose of this study was to identify
osteogenic factors in porcine enamel extracts. METHODS: Enamel proteins were
separated by size-exclusion chromatography into four fractions, which were tested
for their osteogenic activity on osteoblast-like cells (ST2) and human
periodontal ligament (HPDL) cells. RESULTS: Fraction 3 (Fr.3) and a transforming
growth factor-beta 1 (TGF-beta1) control reduced alkaline phosphatase (ALP)
activity in ST2 but enhanced ALP activity in HPDL cells. The enhanced ALP
activity was blocked by anti-TGF-beta antibodies. Furthermore, using a dual
luciferase reporter assay, we demonstrated that Fr.3 can induce the promoter
activity of the plasminogen activator inhibitor type 1 (PAI-1) gene. CONCLUSION:
These results show that the osteoinductive activity of enamel extracts on HPDL
cells is mediated by TGF-beta1.
PMID- 17032112
TI - Changes in periodontal and rheumatological conditions after 2 years in patients
with juvenile idiopathic arthritis.
AB - BACKGROUND: The aim of this study was to monitor changes in periodontal
inflammation in patients with juvenile idiopathic arthritis (JIA) for 2 years. We
investigated the influence of rheumatic disease activity and antirheumatic
medication on clinical and immunological parameters of periodontal inflammation
in these individuals. METHODS: Two years after a baseline examination, the
periodontal and rheumatological conditions of 18 adolescents with JIA and 14
control subjects were described. The clinical periodontal inflammation was
monitored by registration of visual plaque, marginal bleeding, probing depth, and
clinical attachment loss (AL). Periodontal inflammation was also assessed by
analysis of the cytokines interleukin (IL)-1beta and IL-18 and the collagenase
matrix metalloproteinase (MMP)-8 by enzyme-linked immunosorbent assay. RESULTS:
The erythrocyte sedimentation rate and clinical rheumatological parameters were
significantly improved at the 2-year follow-up. The number of sites with plaque
decreased, and the number of pockets >/=4 mm increased, whereas bleeding levels
and the extension of AL remained unchanged. IL-1beta in gingival crevicular fluid
decreased significantly in the JIA group after 2 years. No differences were
observed for IL-1beta, MMP-8, or IL-18 levels between groups after 2 years.
CONCLUSION: Two years after the baseline examination, no clinical or laboratory
differences in periodontal inflammation could be found between JIA patients and
control subjects.
PMID- 17032113
TI - The effects of loading time on osseointegration and new bone formation around
dental implants: a histologic and histomorphometric study in dogs.
AB - BACKGROUND: Immediate loading of dental implants has been introduced as a method
of reducing implant treatment time without compromising its prognosis. In this
research, the effects of loading time on the amount of bone-to-implant contact
and bone formation around dental implants were evaluated histologically. METHODS:
Three months prior to implantation, the lower premolar teeth of 15 dogs were
extracted. Three or four dental implants were placed in the healed extraction
sites for each dog (N = 48). Dividing the dogs into three groups, the implants
were either loaded 48 hours or 1 week later with metallic or prefabricated
acrylic crowns or were left unloaded until the time of sacrifice. Three months
after implant insertion, the animals were sacrificed and samples were
investigated to define the amount of bone-to-implant contact, lamellar and woven
bone percentage, and local inflammation of the newly formed bone. RESULTS: No
significant difference in the observed criteria was reported among the three
groups (P >0.05); however, the unloaded group had the highest degree of bone-to
implant contact and the group loaded 48 hours after the primary implant insertion
had the least. The prosthesis type had no significant effect on the implant
success rate (P >0.05). The lamellar and woven bone percentage of newly formed
bone also did not differ in the three groups (P >0.05). One implant from each
group failed in this study. CONCLUSION: Loading time does not seem to
significantly affect the degree of osseointegration and bone-to-implant contact
and the composition of newly formed bone around dental implants.
PMID- 17032114
TI - Relationship between prereferral periodontal care and periodontal status at time
of referral.
AB - BACKGROUND: According to a recent study, the severity of periodontal disease of
individuals referred for periodontal care is greater now than in 1980.
Variability in the standard of periodontal care in general dental practices may
result in less than desirable outcomes and consequences of poorer periodontal
health. METHODS: A sample of 100 newly referred dental patients from three
separate periodontal practices in the greater Kansas City, Missouri area
participated in this study. Data were collected from three sources: 1) a clinical
chart audit, 2) current periodontal disease status as determined by clinical
examination, and 3) a patient response questionnaire on past professional care
and personal oral care habits. Bivariate analyses were performed using a
statistical package. RESULTS: Of the 100 subjects, 74 were diagnosed as
periodontal case type IV at the point of referral, of which 29.8% were treatment
planned by the periodontist for two or more extractions. Teeth treatment planned
for extraction were significant as a function of disease severity (P = 0.0001).
Periodontal treatment provided in general dental practices did not vary because
of disease severity. The incidence of deep cleanings (scaling and root planing)
was reported slightly higher (32.4%) for case type IV than for case type III
(26.9%), but this difference was not statistically significant. The average
number of cleanings received in the general dental office was less than the
standard of care according to the severity of the disease. CONCLUSION: If one
assumes that the data obtained in the Kansas City practices are representative of
a larger geographic area, it indicates that dentistry may be failing to address
issues of the timely diagnosis of periodontal disease, appropriate treatment,
and/or timely referral for treatment.
PMID- 17032115
TI - Histologic evaluation of implants following flapless and flapped surgery: a study
in canines.
AB - BACKGROUND: Flapless surgery requires penetration of the alveolar mucosa and bone
without reflection of mucoperiosteal flaps. Do these techniques force gingival
tissue or foreign materials into osteotomies? If so, do such tissues or materials
interfere with osseointegration? A proof-of-principle study using a canine model
attempted to answer these questions. METHODS: Five young adult Hound Labrador
mongrel dogs received implants with a moderately roughened surface by anodic
oxidation using flapless or conventional one-stage (control) surgery in
contralateral jaw quadrants. The implants were placed into the osteotomies, and
the international stability quotient (ISQ) was recorded using resonance frequency
analysis. These measurements were repeated following a 3-month healing interval
when the animals were euthanized, and implants and surrounding tissues were
retrieved and processed for histologic analysis. RESULTS: The implants were
stable upon insertion and demonstrated increased stability at 3 months without
significant differences between surgical protocols. The histologic evaluation
showed high bone-implant contact (flapless surgery: 54.7% +/- 8.4%; control:
52.2% +/- 13.0%; P >0.05) without evidence of gingival tissue or foreign body
inclusions. There were no significant differences in marginal bone levels between
the surgical protocols. Post-insertion and at 3 months, ISQ values depended on
the amount of torque delivered. Immediately post-insertion, for every 1-unit
increase in torque value, the ISQ increased by 0.3 (95% confidence interval: 0.1
to 0.4; P = 0.0043). Three months postoperatively, for every one-unit increase in
torque the ISQ value decreased 0.2 (95% confidence interval: -0.4 to -0.1; P =
0.0012). The effect of torque on ISQ values was independent of treatment effects
and remained significant after adjustment for treatment. CONCLUSIONS: The results
suggest that implants placed without flap reflection remain stable and exhibit
clinically relevant osseointegration similar to when implants are placed with
flapped procedures. Greater torque at implant placement resulted in less implant
stability at 3 months.
PMID- 17032117
TI - Selective cyclooxygenase-2 inhibitor may impair bone healing around titanium
implants in rats.
AB - BACKGROUND: The aim of this study was to investigate the effect of a selective
cyclooxygenase-2 inhibitor, meloxicam, on bone healing around titanium implants
in rats. METHODS: Thirty-one adult male Wistar rats were included in this study,
and one screw-shaped titanium implant was inserted in the tibiae of each rat. The
animals were randomly assigned to one of the following groups for daily
subcutaneous injections: control (N = 14): saline solution; and test (N = 17): 3
mg/kg of meloxicam, each administered daily for 60 days. After the treatment,
animals were sacrificed, and undecalcified sections were obtained. Bone-to
implant contact (BIC) and bone area (BA) within the limits of implant threads and
bone density (BD) in a 500 mum-wide zone lateral to the implants were obtained
and arranged for cortical (zone A) and cancellous (zone B) bone regions. RESULTS:
Intergroup comparisons demonstrated that meloxicam significantly reduced bone
healing around implants. For zone A, significant differences were observed
regarding BIC (47.01 +/- 10.48 A; 35.93 +/- 12.25 B), BA (86.42 +/- 3.66 A; 61.58
+/- 12.09 B), and BD (96.86 +/- 0.96 A; 91.06 +/- 3.05 B) for control and test
groups, respectively (P <0.05). For zone B, data analysis also showed significant
differences among groups for BIC (30.76 +/- 13.80 A; 16.86 +/- 11.48 B), BA
(34.83 +/- 8.18 A; 25.66 +/- 9.16 B), and BD (15.76 +/- 7.05 A; 7.73 +/- 4.61 B)
for control and test groups, respectively (P <0.05). CONCLUSION: Meloxicam may
negatively influence bone healing in the cortical and cancellous bone around
titanium implants inserted in rats after continuous administration.
PMID- 17032116
TI - A Hepatocyte Growth Factor (HGF)/receptor autocrine loop regulates constitutive
self-renewal of human periodontal ligament cells but reduces sensitivity to
exogenous HGF.
AB - BACKGROUND: In addition to its prominent role in liver regeneration, hepatocyte
growth factor (HGF) is now generally thought to be produced by mesenchymal cells
to promote the regeneration of epithelial tissue by a paracrine mechanism.
However, it is not known how or if HGF could be involved in the regeneration of
periodontal tissues. The purpose of this study was to characterize the ability of
normal human periodontal ligament (PDL) cells to produce or respond to HGF.
METHODS: PDL cells derived from healthy young volunteers were used from passages
four through 10. HGF receptors were detected both by immunocytochemical staining
and Western-blotting analysis. Both DNA synthesis (by bromo-deoxyuridine [BrdU]
incorporation) and secreted HGF were quantified by enzyme-linked immunosorbent
assays. Mitogen-activated protein kinase (MAPK) phosphorylation was also analyzed
by Western blot. RESULTS: Despite the immunocytochemical demonstration of HGF
receptor protein in the cytoplasm and on the plasma membrane of PDL cells,
exogenous recombinant human HGF did not exert the mitogenic effects expected. As
reported for other mesenchymal cells, PDL cells were found to secrete HGF.
Treatments with neutralizing anti-HGF antibody significantly suppressed
constitutive PDL cell proliferation and sustained the receptor protein at higher
levels than in non-treated cells. Under these conditions, exogenous HGF rapidly
phosphorylated extracellular signal-regulated kinase (ERK), an action linked to
the cell proliferation and downregulation of cell-surface receptors. CONCLUSIONS:
Unlike other known mesenchymal or epithelial cells, these findings suggest that
normal PDL cells from young donors possess a constitutive HGF/receptor autocrine
loop that normally regulates their replacement self-proliferation but reduces
sensitivity to exogenously applied HGF by acute receptor downregulation.
PMID- 17032118
TI - Histologic evaluation of early human bone response to different implant surfaces.
AB - BACKGROUND: Studies have demonstrated that roughened dental implant surfaces show
firmer bone fixation and an increased percentage of bone-to-implant contact
(BIC%) compared to commercially pure titanium-surface (machined) implants.
Therefore, the purpose of this study was to evaluate the influence of implant
surface topography on human bone tissue after 2 months of unloaded healing.
METHODS: Fourteen subjects with a mean age of 46.87 +/- 9.45 years received two
microimplants each (2.5 mm in diameter and 6 mm in length), one test (sandblasted
acid-etched surface) and one control (machined surface), either in the mandible
or in the maxilla. After a healing period of 2 months, the microimplants and
surrounding tissues were removed with a trephine bur and prepared for histologic
analysis. RESULTS: All microimplants, except for one of the controls, were
clinically stable after the healing period. Histometric evaluation indicated that
the mean BIC% was 23.08% +/- 11.95% and 42.83% +/- 9.80% for machined and rough
microimplant surfaces, respectively (P = 0.0005). The bone area within the
threads was also higher for sandblasted-surface implants (P = 0.0005). The mean
percentage of bone density did not differ between the two groups (P = 0.578).
CONCLUSION: Data from the present histological study suggest that the sandblasted
acid-etched implant provides a better human bone tissue response than machined
implants under unloaded conditions after a healing period of 2 months.
PMID- 17032119
TI - The association between cumulative periodontal disease and stroke history in
older adults.
AB - BACKGROUND: Since the late 1980s, several studies have been conducted to
investigate the relationship between periodontal disease and ischemic stroke. The
purpose of this study is to investigate the relationship of periodontal disease
to the self-reported history of stroke in the elderly (60 years of age and older)
by examining the data of the Third National Health and Nutrition Examination
Survey (NHANES III). METHODS: Data from NHANES III, a large population-based
cross-sectional survey of the United States, were used for this study. Because
1,563 of the 5,123 subjects in the study were edentulous, and periodontal disease
is a major cause of tooth loss, it was necessary to account for edentulousness in
the statistical analysis to avoid bias. Hence, a new index called the periodontal
health status (PHS) index was developed to address this problem. Two measures of
PHS were developed: PHS I, based on the median percentage of sites with >/=2 mm
clinical attachment loss (CAL), and PHS II, based on the median percentage of
sites with >/=3 mm CAL. Multiple logistic regression analysis was used to test
for the association of PHS with stroke history. Two types of a multiple logistic
regression model were fit: 1) logistic regression modeling with adjustment for
age and tobacco use only; and 2) logistic regression modeling with adjustment of
all statistically significant confounders. RESULTS: Based on multiple logistic
regression analysis of PHS with adjustment for age and tobacco use only,
completely edentulous elderly adults (PHS Class 5) and partially edentulous
(teeth in one arch) elderly adults with appreciable clinical attachment loss (PHS
Class 4) were significantly more likely to have a history of stroke compared to
dentate adults (teeth in both arches) without appreciable clinical attachment
loss (PHS Class 1). When multiple logistic regression models were fit with
adjustment of all significant confounders, no statistically significant
association was found between PHS and stroke. CONCLUSIONS: Based on the results
of this study, there is evidence of an association between cumulative periodontal
disease, based on PHS, and a history of stroke. However, it is unclear whether
cumulative periodontal disease is an independent risk factor for stroke or a risk
marker for the disease.
PMID- 17032120
TI - Prevalence of different types of accessory canals in the furcation area of third
molars.
AB - BACKGROUND: Although there are several studies that show the prevalence and
diameter of accessory root canals in the furcation area, there is a scarceness of
studies that observe the trajectory and different types of cavo-interradicular
canals. The aim of this study was to verify the prevalence of the different
morphologic types of accessory canals in the furcation region in an attempt to
show their trajectories. METHODS: Forty submerged mandibular third molars were
used, which were extracted and decalcified so that the microtomy procedure in the
mesio-distal axial plane could be performed, obtaining semiserial sections with
thicknesses of 5 microm. The sections were stained with hematoxylin and eosin and
observed under optical microscopy. RESULTS: All of the morphologic types were
found, whereas the proper accessory canals, type-A canals, were present in 10% of
the specimens. The most prevalent canals were the sealed ones (type D), with a
prevalence of 87.5%, followed by the blind ones (type B), with a prevalence of
75%. The loop accessory canals (type C), observed in only 5% of the teeth, were
the least prevalent ones. CONCLUSIONS: Different morphologic types of accessory
canals were found in the furcation area of submerged mandibular molars. The
histologic method was effective to show the canal trajectories.
PMID- 17032121
TI - Local gingival blood flow at healthy and inflamed sites measured by laser Doppler
flowmetry.
AB - BACKGROUND: This investigation aimed to: 1) develop a method to obtain
reproducible laser Doppler flow readings (LDFRs) at the gingiva of the maxillary
front teeth; 2) evaluate regional gingival blood flow (GBF) in healthy gingiva by
laser Doppler flowmetry; 3) compare hand-held LDFR (H-LDFR) with splint LDFR (S
LDFR); and 4) monitor changes in GBF in experimental gingivitis (EG) and chronic
gingivitis (CG). METHODS: The LDFR, gingival index (GI), and plaque index (PI)
were measured at 13 gingival sites (teeth #6 to #11) in 10 healthy volunteers
(five males and five females), 23 to 34 years of age, over a period of 12.5 +/-
3.27 days employing a partial-mouth EG model and in 11 patients (three males and
eight females), 20 to 63 years or age, with CG. LDFRs were obtained by S-LDFR or
H-LDFR. RESULTS: H-LDFRs were significantly higher than S-LDFRs (P <0.05). All EG
subjects developed gingivitis (PI: 2.77 +/- 0.23; GI: 1.5 +/- 0.53). EG-LDFRs at
diseased sites increased slightly but not significantly over the study period.
All CG-patients had high plaque and inflammation scores (PI: 2.8 +/- 0.2; GI:
1.63 +/- 0.78). CG-LDFRs at sites with GI >1 were significantly higher than LDFRs
at healthy sites (P <0.05). CG-LDFRs were significantly higher than EG-LDFRs at
sites with a comparable GI (P <0.05). CONCLUSIONS: LDFRs are positively
correlated with the degree of gingival inflammation. GBF demonstrated significant
differences in EG and CG. Modifications of the probe are needed to enhance its
clinical applicability in clinical research of periodontal diseases.
PMID- 17032122
TI - High expression levels of receptor activator of nuclear factor-kappa B ligand
associated with human chronic periodontitis are mainly secreted by CD4+ T
lymphocytes.
AB - BACKGROUND: Chronic periodontitis is an infectious disease characterized by
alveolar bone destruction and teeth loss. Receptor activator of nuclear factor
kappa B ligand (RANKL) is an osteoclastogenic cytokine, a central regulatory
factor in the osteoclast's lifespan, and a participant in physiological and
pathological bone resorption. Gingival T cells synthesize RANKL, contributing to
molecular local imbalance that entails the alveolar bone resorption seen in
periodontitis. Our study was aimed at associating the levels of RANKL with the
CD4(+) T-cell activity present in gingival tissues of chronic periodontitis
patients. METHODS: Gingival biopsies were obtained from 33 chronic periodontitis
patients and 20 healthy controls. Specimens were either formalin fixed and
paraffin embedded for real-time reverse transcription-polymerase chain reaction
(RT-PCR) and histologic analysis or tissue digestion processed for cell culture
and flow-cytometry analysis. RANKL mRNA and protein levels were determined by
quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) in gingival
cell culture supernatants. Gingival leukocytes were quantified by flow cytometry.
RANKL and CD4 immunoreactivity were analyzed by flow cytometry and confocal
microscopy. RESULTS: RANKL mRNA levels were higher in patients with periodontitis
than in healthy subjects, and spontaneous and lipopolysaccharide (LPS)- and
phytohemagglutinin (PHA)-stimulated RANKL synthesis were higher also in patients
than controls. CD4(+) T lymphocytes were the predominant infiltrate cell subset
present in gingival tissues of periodontitis patients. Furthermore, an
association between RANKL and CD4(+) T cells was determined by double-staining
flow cytometry and confocal microscopy. CONCLUSION: Taken together, these data
demonstrate that gingival CD4(+) T cells are the main cells responsible for
higher levels of RANKL observed in human chronic periodontitis patients.
PMID- 17032123
TI - Bioabsorbable membrane and bioactive glass in the treatment of intrabony defects
in patients with generalized aggressive periodontitis: results of a 5-year
clinical and radiological study.
AB - BACKGROUND: The aim of this clinical and radiological prospective 5-year study
was to compare the long-term effectiveness of a bioabsorbable membrane and a
bioactive glass in the treatment of intrabony defects in patients with
generalized aggressive periodontitis. METHODS: Sixteen patients (11 women and
five men) with generalized aggressive periodontitis were enrolled in the study.
The investigations were confined to 1- to 3-walled intrabony defects with a depth
>/=4 mm and with preoperative probing depths (PDs) >/=7 mm. Teeth with furcation
involvement were excluded. Twenty-two of the defects were treated with the
membrane (RXT group) and 20 with the bioactive glass (PG group). Allocation to
the two groups was randomized. The clinical parameters plaque index (PI),
gingival index (GI), PD, bleeding on probing (BOP), gingival recession (GR),
clinical attachment level (CAL), and tooth mobility were recorded before surgery
and at 6 months and every year for 5 years after surgery. Intraoral radiographs
were taken using a standardized paralleling technique at baseline and every year
for 5 years. Statistical analysis was based on Kolmogorov-Smirnov and Wilcoxon
signed-rank tests, analysis of covariance, and Spearman's bivariate correlation
analysis. RESULTS: After 5 years, a reduction in PD of 3.6 +/- 0.8 mm (P = 0.016)
and a gain in CAL of 3.0 +/- 2.0 mm (P = 0.01) were registered in the RXT group.
There was a slight increase in GR by 0.6 +/- 1.4 mm (P = 0.334). In the PG group,
a reduction in PD of 3.5 +/- 1.4 mm (P = 0.01) and a gain in CAL of 3.3 +/- 2.1
mm (P = 0.01) were recorded, whereas GR increased by 0.2 +/- 1.7 mm (P = 0.525).
The 1-, 2-, 3-, and 4-year results did not differ significantly from the 5-year
results. Radiographically, the defects (the point on the proximal surface of the
defective tooth at which the projected alveolar crest intersected the root
surface [xCA] to the most coronally located point at the proximal surface of the
tooth on the defect side up to which the periodontal ligament space still
displayed a uniform width [xBD]) were found to be filled by 47.5% +/- 38.3% (P =
0.001) in the RXT group and by 65.0% +/- 50.5% (P = 0.001) in the PG group.
Crestal resorption (the most apical point of the enamel at the proximal surface
of the tooth on the defect side [xCEJ] to the xCA) was 19.0% +/- 30.2% (P =
0.374) in the RXT group and 12.3% +/- 38.6% (P = 0.647) in the PG group. The xCEJ
to the xBD was significantly more in the PG group (28.4 +/- 24.6 versus 7.3 +/-
21.8, P = 0.048). A good standard of oral hygiene and inflammation-free
periodontal tissue in the postoperative phase improved the treatment outcome. No
dependence of attachment gain was found on the tooth type, number of walls
involved in the defects (r = 0.075; P = 0.319), or intraoperative depth (r =
0.114; P = 0.307). CONCLUSIONS: Highly significant improvements in the parameters
PD and CAL were recorded after 5 years with both regenerative materials.
Radiographically, the defects (the xCED to the xBD) were found to be filled
significantly more in the bioactive glass group. A good standard of oral hygiene
and inflammation-free periodontal tissue in the postoperative phase improved the
treatment outcome.
PMID- 17032124
TI - The papilla amplification flap for the treatment of a localized periodontal
defect associated with a palatal groove.
AB - BACKGROUND: Teeth with a palatal groove often present with severe localized
periodontal attachment loss including pocket formation and alveolar bone loss.
The aim of the present case report was to describe the regenerative surgical
treatment of periodontal and bone lesions associated with the subgingival
extension of a palatal groove affecting a maxillary lateral incisor. METHODS: The
left maxillary lateral incisor of a systemically healthy young subject presented
with a palatal probing depth of 10 mm with no gingival recession at the buccal
and palatal surfaces; the neighboring interdental papillae were intact. The
radiograph showed a radiolucency area distal to the affected tooth. Treatment
procedures consisted of: 1) the papilla amplification flap with the use of enamel
matrix proteins as the regenerative periodontal material; 2) the
elimination/flattening of the radicular portion of the palatal groove; and 3) the
sealing of the coronal portion of the groove with composite flow. RESULTS: The
clinical examination at 1 year revealed a clinical attachment gain (8 mm) with a
shallow residual probing depth (2 mm) and no increase in gingival recession. The
radiographic examination showed the complete disappearance of the radiolucency
area suggesting bone fill. CONCLUSIONS: The present study indicated that
localized periodontal defects associated with a palatal groove can be
successfully treated by means of the papilla amplification flap with the use of
enamel matrix protein as the regenerative material. The long-term stability of
such successful results needs to be determined.
PMID- 17032125
TI - Solitary superficial microcystic lymphatic malformation (lymphangioma
circumscriptum) of the gingiva.
AB - BACKGROUND: Lymphatic malformations are uncommon, hamartomatous, developmental
aberrations of the lymphatic system. The case presented in this report is a rare
solitary gingival involvement of a microcystic-type lymphatic malformation.
METHODS: The lesion presented clinically as a small vesicular swelling of a
buccal interdental papilla in a 16-year-old girl. Involved tissues were excised
and submitted for routine histologic examination. The expression of the
endothelial marker CD34 was investigated using immunohistochemical staining.
RESULTS: A physical examination failed to reveal similar or other abnormalities
elsewhere in the body of the patient, including the oral cavity. Histopathologic
analysis of the specimen demonstrated the presence of subepithelial, thin-walled,
distended vascular cavities forming confluent vesicles containing lymph. The
dilated lymphatic formations were lined by flattened CD34-negative endothelial
cells. These features were consistent with a microcystic gingival lymphatic
malformation. To the best of our knowledge, only two additional reports of this
malformation have been published to date, but both presented with bilateral
gingival involvement. CONCLUSION: Even though lymphatic malformations are
encountered very infrequently on gingiva, they should be considered in the
differential diagnosis of related conditions with a vesicular clinical
appearance.
PMID- 17032126
TI - Multiplexed testing in the autoimmunity laboratory.
AB - A variety of technologies for autoantibody profiling have been developed. The
main techniques are line-blot immunoassays, bar-coded nanoparticle immunoassays,
and bead-based assays with flow cytometry detection and antigen microarrays. Some
of these technologies are only able to measure a limited number of
autoantibodies, while others can detect elevated numbers. Assays for antinuclear
antibody specificities using line-blot immunoassays and bead-based assays with
flow cytometry detection are already commercialised. Antigen microarrays for
autoantibody measurement are only in the development phase, although in the not
too distant future these assays will probably appear on the market. Multiplexed
testing in the autoimmunity laboratory appears to have a promising future, since
this technique permits a reduction in analytical time, with a shorter turnaround
time.
PMID- 17032127
TI - Uncertainty calculation for calibrators and controls of laboratory diagnostic
assays.
AB - The uncertainty of the results from calibrators and controls is an important
component of the overall uncertainty of the results of medical samples. The
purpose of this note is to review procedures of standardization and to describe
the respective calculation of the uncertainty components for calibrators and
controls of commercial routine diagnostic assays. The authors hope that the
laying out of the procedures for uncertainty calculation of routine calibrators
and controls contributes (i) to the transparency on how this component of
uncertainty is derived and (ii) to a better understanding and use of the
uncertainty concept in the routine laboratory.
PMID- 17032128
TI - Westgard multirule for calculated laboratory tests.
AB - BACKGROUND: In clinical laboratories, many test results such as low-density
lipoprotein (LDL)-cholesterol can be calculated using the results of specifically
measured tests. However, quality control programs deal only with measured tests
and there is no adequate quality assessment procedure for calculated tests. I
aimed to apply the Westgard multirule to calculated tests as a part of routine
quality procedures. METHODS: I prepared a Levey-Jennings chart for calculated
tests and all their measured components (Equation chart) and then applied the
Westgard multirule to these tests. RESULTS: Applying the Westgard multirule to
calculated LDL-cholesterol (and other calculated tests) was simple, and increased
the reliability of the results of the calculated tests. CONCLUSIONS: Checking the
reliability of only measured tests by quality control procedures before reporting
patient results may be inadequate. Applying the Westgard multirule to calculated
tests as part of total quality management will increase the reliability of test
results.
PMID- 17032129
TI - Frequency of a single nucleotide (A2317G) and 56-bp variable number of tandem
repeat polymorphisms within the deoxyribonuclease I gene in five ethnic
populations.
AB - BACKGROUND: The single nucleotide polymorphism (SNP) at deoxyribonuclease I
(DNase I), designated as DNASE1 (NCBI SNP number; 1053874), in exon 8 (A2317G) is
considered to be one of the susceptibility genes for gastric and colorectal
carcinoma and myocardial infarction. Recently, the presence of a variable number
of tandem repeat (VNTR) polymorphisms, designated as HumDN1, in intron 4 was
found. METHODS: Simultaneous genotyping of the DNASE1 and HumDN1 polymorphisms
within the DNase I gene was performed in Ovambo, Turkish, Mongolian, Korean, and
Japanese populations. RESULTS: The allele frequencies of the DNASE1 and HumDN1
loci differed among five populations. There was general uniformity for the two
polymorphisms in the three Asian populations, but significant differences in
genotype distribution between the Ovambo and Turkish populations. The DNASE1 *1
and HumDN1 *3 alleles were found to be the most predominant among the Ovambos.
Turks had the highest allele frequency for DNASE1 *2, HumDN1 *4, and HumDN1 *5. A
linkage disequilibrium between the single-nucleotide (A2317G) and 56-bp VNTR
polymorphisms was revealed in all populations except the Ovambos. CONCLUSIONS:
This study is the first to demonstrate the simultaneous genotyping of DNASE1 and
HumDN1 polymorphisms and reveal the existence of a certain genetic heterogeneity
in the worldwide distribution of these two polymorphisms. The combination of the
two polymorphisms within a DNase I gene may be potentially useful for clinical
purposes and in population genetic studies.
PMID- 17032130
TI - The influence of genetic polymorphisms of cytochrome P450 3A5 and ABCB1 on
starting dose- and weight-standardized tacrolimus trough concentrations after
kidney transplantation in relation to renal function.
AB - BACKGROUND: Cytochrome P450 3A5 (CYP3A5) and ABCB1 polymorphisms have been shown
to influence tacrolimus (Tc) blood concentrations in the stable phase after organ
transplantation. We hypothesized that Tc pharmacokinetics may be affected by
genetic mutations subsequent to starting doses. METHODS: We retrospectively
analyzed data from a cohort of 59 kidney transplant recipients, in whom CYP3A5
(intron 3) and ABCB1 (exons 12, 21 and 26) genotypes were correlated to dose- and
weight-standardized Tc trough concentrations obtained after initial Tc doses.
Renal function, expressed as glomerular filtration rate (GFR) (MDRD equation), on
days 7 and 14 after transplantation was evaluated and its relationship with Tc
concentrations was analyzed. RESULTS: Dose- and weight-standardized Tc trough
concentrations were lower in patients carrying the CYP3A5 *1 allele (p<0.01).
There was no statistically significant association with ABCB1 polymorphisms. In a
multivariate analysis, both the presence of at least one CYP3A5 *1 allele
(p=0.006) and age at the time of transplantation (p=0.010) were significant
independent variables affecting Tc trough blood concentrations standardized to
the first dosages (model r2=0.23). GFR was not affected by Tc concentrations.
CONCLUSIONS: Prospective trials are needed to prove that a genetic approach to Tc
pharmacokinetics and its related side effects during the early period after
grafting may improve patient outcome.
PMID- 17032131
TI - Apolipoprotein B gene 3'VNTR polymorphism: association with plasma lipids and
coronary heart disease in Han Chinese.
AB - BACKGROUND: Studies that considered polymorphisms within the apolipoprotein B
(APOB) gene as risk factors for coronary heart disease (CHD) have reported
conflicting results. METHODS: The phenotypic effects of the 3'VNTR polymorphism
of the APOB gene on the susceptibility to CHD were investigated in 120 unrelated
healthy individuals and 137 CHD patients. The internal structure of APOB gene
3'VNTR alleles was also analyzed by the methods of SspI restriction mapping and
DNA sequencing of the allele fragments. RESULTS: In total, 14 segregating alleles
and 32 genotypes of APOB gene 3'VNTR were characterized in the pooled total of
257 subjects. The frequency of 3'VNTR-B alleles [hypervariable element (HVE) > or
=38)] in the CHD cases was higher than that of the controls (10.95% vs. 5.00%,
p<0.05). 3'VNTR-B allele was dependently related to total cholesterol levels
(p<0.05). Compared with SS homozygotes, 3'VNTR-B allele carriers were associated
with an increased risk of CHD (OR=2.137, 95% CI=1.055-4.328, p=0.0349). No
significant differences in the internal structure and sequences of APOB gene
3'VNTR alleles were found between cases and controls. CONCLUSIONS: APOB gene
3'VNTR polymorphism exerts an impact on lipid metabolism and may contribute to
the susceptibility to the development of CHD in Han Chinese.
PMID- 17032132
TI - Paraoxonase-1 (PON1) activity, but not PON1(Q192R) phenotype, is a predictor of
coronary artery disease in a middle-aged Serbian population.
AB - BACKGROUND: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated
serum enzyme that protects lipoproteins from oxidative modifications.
Polymorphisms in the gene, including PON1Q192R, have been studied. However,
inconsistencies regarding the above-mentioned polymorphism obscure its
association with vascular disease. METHODS: Using a two-substrate
(paraoxon/diazoxon) activity method, we investigated the frequencies of PON1Q192R
phenotypes in 261 middle-aged subjects: 156 patients with angiographically
assessed coronary heart disease (CHD) and 105 CHD-free subjects as the control
group. The PON1(192) phenotype was predicted from examination of the two
dimensional plot of hydrolysis rates of diazoxon vs. paraoxon and by using the
antimode of the histogram of the ratio of diazoxonase/paraoxonase activity.
RESULTS: The PON1Q192R phenotype frequencies in 113 patients with occlusion >50%
(coronary artery disease-positive, CAD+ group) vs. control population were as
follows: QQ (0.552 vs. 0.510), QR (0.382 vs. 0.408) and RR (0.066 vs. 0.082);
chi2=0.414, p=0.813. We found lower paraoxonase (POase) and diazoxonase (DZOase)
activities in the CAD+ patients when compared to the control population.
According to logistic regression analysis, POase activity was a better predictor
of coronary disease onset compared with DZOase activity measurements and
PON1Q192R phenotyping. CONCLUSIONS: We conclude that enzyme activity (within a
particular phenotypic group) is more important than phenotype alone in predicting
susceptibility to coronary artery disease.
PMID- 17032133
TI - A modified method of prothrombin time/International Normalised Ratio
determination in capillary blood and monitoring oral anticoagulant therapy.
AB - BACKGROUND: Oral anticoagulant therapy is monitored by a prothrombin time (PT)
assay. The PT is standardised by the International Normalised Ratio (INR). The
purpose of this study was to work out a modified method of PT/INR measurement in
capillary blood for monitoring anticoagulation treatment. METHODS: Healthy
donors, subjects with high or low haematocrit values, and oral anticoagulant
treated patients were included in the study. Plasma and capillary blood PT/INRs
were determined by the standard Quick clotting assay, by the modified approach
and with the CoaguChek S analyser. RESULTS: The performance characteristics of
the developed method were accuracy, due to taking into account whole capillary
blood haematocrit values, and precision, due to a decrease in the viscosity of
the analysed samples. Implementation of the modified method showed that it is
possible to use PT values of normal plasma for capillary blood INR calculation.
The developed method allowed the determination of PT in capillary blood within
the haematocrit value range from 0.15 up to 0.7. For capillary blood, the results
of the modified method closely correlated with PT/INR values determined by the
reference Quick method in venous plasma (r=0.99) and with the CoaguChek S
analyser (r=0.97). CONCLUSIONS: The modified method of capillary blood PT/INR
determination could be recommended for oral anticoagulant therapy monitoring.
PMID- 17032134
TI - Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.
AB - BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally
active in atherosclerosis (AS) lesions. Aspirin was found to be a potent
inhibitor of the UPS in some tumour studies; however, its effect on AS remains to
be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal
diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without
(H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of
plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin
conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65
were investigated by Western blotting or immunochemistry. RESULTS: Concentrations
of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI.
Histological analysis showed that atheroma was increased in H. Ub and
IkappaBalpha were mainly localised in subendothelium and media vascular smooth
muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha
were increased, whereas p65 was lower in HI vs. H. The activity of the 20S
proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome
was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the
pathogenesis of atheroma formation, the degradation of IkappaBalpha and
pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic
effects on AS may be via inhibition of the UPS.
PMID- 17032135
TI - Lipid peroxidation and antioxidative status in beta-thalassemia major patients
with or without hepatitis C virus infection.
AB - BACKGROUND: Information pertaining to the lipid peroxidation and antioxidative
status of patients with beta-thalassemic major, with or without hepatitis C virus
infection, has been scanty. METHODS: We report here the results of our efforts in
the evaluation of lipid peroxidative status, antioxidants, and vitamin A, E and C
levels in the sera of a group of patients (n=42) with transfusion-dependent beta
thalassemic major with or without HCV infection. RESULTS: Firstly, plasma
thiobarbituric acid reactive substance, a lipid peroxidation product, in these
patients was found to be increased significantly when compared to the disease
free controls (p<0.05). Conversely, levels of plasma vitamins A, E and C were all
shown to be drastically reduced as compared to the disease-free controls
(p<0.01). In parallel with these data, we also found that HCV infection did play
some role in aggravating the depletion of plasma vitamin E and C levels in the
beta-thalassemic patients. In contrast, HCV infection did not seem to alter the
levels of reduced glutathione (GSH) as well as antioxidant enzyme activities
including superoxide dismutase and GSH peroxidase. CONCLUSIONS: Taken together,
our data indicate that excessive lipid peroxidation and a profound depletion of
plasma vitamin A, E and C levels exist in patients with beta-thalassemic major.
These data suggest that antioxidant supplementation to the patients for the
purpose of alleviating the oxidative stress may be warranted.
PMID- 17032136
TI - Role of serum S100B as a predictive marker of fatal outcome following isolated
severe head injury or multitrauma in males.
AB - BACKGROUND: Severe traumatic brain injury (TBI) is associated with a 30%-70%
mortality rate. S100B has been proposed as a biomarker for indicating outcome
after TBI. Nevertheless, controversy has arisen concerning the predictive value
of S100B for severe TBI in the context of multitrauma. Therefore, our aim was to
determine whether S100B serum levels correlate with primary outcome following
isolated severe TBI or multitrauma in males. METHODS: Twenty-three consecutive
male patients (age 18-65 years), victims of severe TBI [Glasgow Coma Scale (GCS)
3-8] (10 isolated TBI and 13 multitrauma with TBI) and a control group consisting
of eight healthy volunteers were enrolled in this prospective study. Clinical
outcome variables of severe TBI comprised: survival, time to intensive care unit
(ICU) discharge, and neurological assessment [Glasgow Outcome Scale (GOS) at ICU
discharge]. Venous blood samples were taken at admission in the ICU (study
entry), 24 h later, and 7 days later. Serum S100B concentration was measured by
an immunoluminometric assay. RESULTS: At study entry (mean time 10.9 h after
injury), mean S100B concentrations were significantly increased in the patient
with TBI (1.448 microg/L) compared with the control group (0.037 microg/L) and
patients with fatal outcome had higher mean S100B (2.10 microg/L) concentrations
when compared with survivors (0.85 microg/L). In fact, there was a significant
correlation between higher initial S100B concentrations and fatal outcome
(Spearman's =0.485, p=0.019). However, there was no correlation between higher
S100B concentrations and the presence of multitrauma. The specificity of S100B in
predicting mortality according to the cut-off of 0.79 microg/L was 73% at study
entry. CONCLUSIONS: Increased serum S100B levels constitute a valid predictor of
unfavourable outcome in severe TBI, regardless of the presence of associated
multitrauma.
PMID- 17032138
TI - Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism.
AB - BACKGROUND: The vesicant agents sulfur and nitrogen mustards, which contain
chloroethyl groups, are potent inhibitors of DNA synthesis and cell growth,
likely changing the utilization of anaerobic glycolysis for energy generation.
METHODS: To investigate the effect of nitrogen mustard on cellular energy
metabolism, lymphocytes treated with increasing doses of mechlorethamine (HN2), a
nitrogen mustard and an analogue of sulfur mustard, were incubated with
radiolabeled glucose. The rates of aerobic and anaerobic glycolysis were then
determined. RESULTS: Glycogen consumption was significantly higher in cells
treated with HN2 in a dose-dependent manner compared to untreated cells.
Similarly, the amount of end-product lactate was increased, but CO2 was reduced
in HN2-treated cells. CONCLUSIONS: Lymphocytes normally use aerobic glycolysis
under aerobic conditions, but energy metabolism predominantly involved anaerobic
glycolysis after severe intoxication with mustard agent.
PMID- 17032137
TI - Preanalytical and analytical variation of surface-enhanced laser desorption
ionization time-of-flight mass spectrometry of human serum.
AB - BACKGROUND: Surface-enhanced laser desorption-ionization time-of-flight (SELDI
TOF) mass spectrometry of human serum is a potential diagnostic tool in human
diseases. In the present study, the preanalytical and analytical variation of
SELDI-TOF mass spectrometry of serum was assessed in healthy individuals.
METHODS: Serum and plasma were obtained from healthy human individuals. Protein
peaks in human serum and plasma were determined by SELDI-TOF mass spectrometry.
RESULTS: The protein peaks in serum in healthy individuals showed no variation
with gender, age, fasting, or diurnal rhythm. The intensity of protein peaks
changed significantly during clotting of serum from 30 to 60 min, followed by
smaller changes from 60 to 120 min. The intensity of protein peaks changed after
60-min storage of serum at room temperature, whereas no changes were observed for
storage on ice. The number of reproducible protein peaks in serum was determined
on WCX2, SAX2, and IMAC30 arrays as 29, 34, and 36, respectively. The average
coefficient of variation (CV) of the mass value of protein peaks was 0.03%. The
intra-assay CV of peak intensity on IMAC30 arrays was 16% (10%-36%, n=8) for 36
peaks, inter-assay CV was 18% (6%-34%, n=4) for 16 peaks, and inter-individual CV
was 38% (16%-56%, n=16) for 20 peaks. CONCLUSIONS: The pre-analytical and
analytical conditions of SELDI-TOF mass spectrometry of serum have a significant
impact on the protein peaks, with the number of peaks low and the assay variation
high. Consequently, SELDI-TOF mass spectrometry of serum needs further evaluation
before application in clinical diagnostics.
PMID- 17032139
TI - Partitioning reference values of several Gaussian subpopulations with unequal
prevalence--a procedure with computer program support.
AB - BACKGROUND: To be able to interpret laboratory values, it is essential to develop
population-based reference intervals. A crucial consideration is whether a
reference interval should be divided into subpopulations or not, so-called
partitioning. There are established methods for deciding whether partitioning
should be done or not. However, these methods are only applicable when
partitioning into two subpopulations is considered. The primary aim of this study
was to suggest a procedure that was also valid for several subpopulations. The
method assumes that these subpopulations are Gaussian. Furthermore, a secondary
aim was to provide a tailor-made computer program to support calculations.
METHODS: The fundamental idea is to partition reference intervals if the
proportions of the distributions of the subpopulations outside the combined
reference limit deviate from the nominal value of 0.025. This is made possible by
finding the combined reference interval using an equation solver algorithm.
RESULTS: It was found that an equation solver algorithm could easily identify the
combined reference interval when combining two or more subpopulations, even if
these subpopulations had unequal prevalences. It was also found that this could
be done even if the ratio between samples does not reflect the ratio between
prevalences. Using this algorithm, it was possible to study whether the
proportion outside the combined reference limits in any of several subpopulations
deviated from the nominal 0.025 by such a magnitude that partitioning was
recommended. When similar figures to those found in earlier studies with other
methods were tested, the procedure showed consistent results with these methods.
The procedure was also found to be applicable when several subpopulations were
considered. As a practical result of the study, a tailor-made computer program
was developed and is now provided over the Internet. CONCLUSIONS: The suggested
procedure could serve as an alternative or complement to existing methods. The
procedure provides calculations of the combined reference interval, even if
sample fractions do not reflect prevalence fractions. The important advantage
with the suggested procedure is the generalisation to the situation when several
Gaussian subpopulations, possibly with unequal prevalences, are considered.
Finally, since a tailor-made computer program is provided, the procedure is
simple to use.
PMID- 17032140
TI - Biovariability of plasma adiponectin.
AB - BACKGROUND: Adiponectin is a cytokine produced by adipose tissue with insulin
sensitising and anti-atherosclerotic effects. Low plasma adiponectin levels are
used as a marker of the metabolic syndrome and incipient type 2 diabetes.
METHODS: We carried out a series of studies to determine the short- and long-term
variability of plasma adiponectin levels, including diurnal and post-prandial
changes. These investigations also included examining the effect of frozen
storage on plasma adiponectin levels. RESULTS: A nested study in 10 overweight
subjects with the metabolic syndrome and 10 age- and sex-matched controls showed
intra-subject variation in adiponectin levels over a 30-day period of 12.2% and
18.8%, respectively, equivalent to reference change values of 1.7 and 3.6
microg/mL. In non-obese subjects, plasma adiponectin levels varied minimally over
a 15-month period (baseline, 8.3+/-2.9 microg/mL vs. +15 months, 8.2+/-3.0
microg/mL, p=0.95) and showed only minor diurnal and post-prandial changes (pre
meal, 8.2+/-3.0 microg/mL vs. 3 h post-prandial, 8.3+/-3.1 microg/mL, p=0.60).
The adiponectin assay had an intra-assay variation of 8.8%, with storage at -30
degrees C for 33 months or three cycles of freezing and thawing having no
discernible effect on adiponectin levels. CONCLUSIONS: These results demonstrate
that plasma adiponectin levels have relatively low biovariability and that
adiponectin can be sampled fasting or non-fasting to provide a reliable marker of
insulin resistance and incipient type 2 diabetes.
PMID- 17032141
TI - Multicentre evaluation of a new point-of-care test for the determination of NT
proBNP in whole blood.
AB - BACKGROUND: The Roche CARDIAC proBNP point-of-care (POC) test is the first test
intended for the quantitative determination of N-terminal pro-brain natriuretic
peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected
congestive heart failure, in the monitoring of patients with compensated left
ventricular dysfunction and in the risk stratification of patients with acute
coronary syndromes. METHODS: A multicentre evaluation was carried out to assess
the analytical performance of the POC NT-proBNP test at seven different sites.
RESULTS: The majority of all coefficients of variation (CVs) obtained for within
series imprecision using native blood samples was below 10% for both 52 samples
measured ten times and for 674 samples measured in duplicate. Using quality
control material, the majority of CV values for day-to-day imprecision were below
14% for the low control level and below 13% for the high control level. In method
comparisons for four lots of the POC NT-proBNP test with the laboratory reference
method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept
ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the
POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test
investigated showed excellent agreement, with mean differences of between -5% and
+4%. No significant interference was observed with lipaemic blood (triglyceride
concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to
582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L),
biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52
standard or cardiological drugs in therapeutic concentrations. With bisoprolol
and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175
ng/L) was found. Haematocrit values between 28% and 58% had no influence on the
test result. Interference may be caused by human anti-mouse antibodies (HAMA)
types 1 and 2. No significant influence on the results with POC NT-proBNP was
found using volumes of 140-165 muL. High NT-proBNP concentrations above the
measuring range of the POC NT-proBNP test did not lead to false low results due
to a potential high-dose hook effect. CONCLUSIONS: The POC NT-proBNP test showed
good analytical performance and excellent agreement with the laboratory method.
The POC NT-proBNP assay is therefore suitable in the POC setting.
PMID- 17032142
TI - Innotrac Aio!: a point-of-care or a routine analyzer? Analytical performance and
plasma/whole blood comparison.
AB - BACKGROUND AND METHODS: The aim of the present study was to evaluate the
analytical performance of the Innotrac Aio! analyzer in measuring the cardiac
markers troponin I (TnI), myoglobin (Myo) and creatine kinase-MB (CK-MB), both in
lithium heparin plasma and in whole blood. RESULTS: TnI analytical sensitivity
was 0.012 microg/L and the concentration corresponding to CV=10% was 0.036
microg/L. In healthy subjects, the 99th percentile TnI values were 0.023 and
0.016 microg/L in whole blood and in plasma, respectively. One hundred samples
were tested both in whole blood and in plasma: TnI-whole-blood=1.16-plasma+0.011,
bias=+0.18 (95% CI from -0.22 to +0.59); Myo-whole-blood=1.04-plasma-1.93,
bias=+1.08 (95% CI from -6.17 to +8.32); CK-MB-whole-blood=1.11-plasma-0.09,
bias=+0.96 (95% CI from -0.53 to +2.45). The method comparison with the RxL
Dimension analyzer for TnI and Myo gave the following results: TnI Aio!=0.30 TnI
RxL+0.00; bias=-5.80 (95% CI from -7.81 to -3.78), Myo Aio!=1.33 Myo RxL+0.42,
bias=+53.09 (95% CI from +38.44 to +67.74). CONCLUSIONS: The analytical
performance of the Innotrac Aio! analyzer was satisfactory for all three cardiac
markers evaluated and, in particular, the TnI method provided sensitive and
accurate results. The most important finding in this study is the possibility to
perform the tests as either routine or point-of-care analysis, thus overcoming
the variability of results obtained employing different methods.
PMID- 17032143
TI - Serologic associations of anti-cytoplasmic antibodies identified during anti
nuclear antibody testing.
AB - BACKGROUND: There are currently no guidelines concerning additional laboratory
testing for specific autoantibodies among anti-nuclear antibody-negative sera
with an anti-cytoplasmic staining pattern identified by indirect
immunofluorescence assay. Moreover, few data are available that address this
laboratory situation. METHODS: We performed specific autoantibody assays in 200
sera with an anti-nuclear antibody titer < or =1:32 and a cytoplasmic titer
(undefined staining pattern) of > or =1:64, identified sequentially in the course
of routine anti-nuclear antibody testing. RESULTS: A total of 85 sera (42.5%)
were positive in one (n=57) or more (n=28) of the specific autoantibody tests
performed. Autoantibodies identified were antimitochondrial (15%), antimicrosomal
(13%), anti-neutrophil cytoplasmic (10%), anti-smooth muscle (6%), anti-parietal
cell (4%), and extractable nuclear antigen (8.5%, including histones, SSA, SSB,
Sm, Jo-1 or Scl-70). A positive result in one or more of these assays was more
frequent at anti-cytoplasmic titers > or =1:1024 (77.8%) than at titers of 1:64
1:128 (7%) (chi2=25.3, p<0.001). CONCLUSIONS: The present data demonstrate that
undefined anti-cytoplasmic staining in anti-nuclear antibody-negative sera is
associated with, although not necessarily caused by, a high frequency and wide
range of specific autoantibodies. Further work is needed before specific
recommendations can be made concerning follow-up in subjects with this laboratory
finding.
PMID- 17032144
TI - The importance of metrological traceability on the validity of creatinine
measurement as an index of renal function.
AB - The glomerular filtration rate (GFR) is currently considered the best overall
index of kidney function. The possibility that laboratories might routinely
report an estimated GFR has become practically feasible with the development of a
formula, the "four-variable" Modification of Diet in Renal Disease study (MDRD)
equation that uses age, sex, race, and serum creatinine parameters. However, a
limitation of this equation for general implementation in healthcare is related
to the use of differently calibrated creatinine measurement procedures among
laboratories. The only way to achieve universal implementation of the GFR
prediction equation, with the associated clinical benefits for patients, is,
therefore, to promote worldwide standardization of methods to determine
creatinine, together with the introduction of a revised GFR-estimating equation
appropriate for use with standardized creatinine methods.
PMID- 17032145
TI - Effect of seropositive rheumatoid factor on cardiac troponin I measurement using
the Access immunoassay analyzer.
PMID- 17032146
TI - Associations between homocysteine, bone turnover, BMD, mortality, and fracture
risk in elderly women.
AB - Homocysteine has been suggested to be a risk factor for fracture, but the causal
relationship is not clear. In 996 women from the OPRA study, high homocysteine
level was associated with high bone marker levels and low BMD at baseline. During
a mean 7-year follow-up, high homocysteine level was associated with mortality,
but no clear association to fracture risk existed. INTRODUCTION: Recently, the
association between high serum homocysteine (Hcy) levels and an increased risk of
fracture has been described. MATERIALS AND METHODS: Hcy levels were measured at
baseline in 996 women, all 75 years old. Vitamin B(12), folate, serum cross
linking telopeptide of type I collagen (CTX), serum TRACP5b, serum osteocalcin,
urine deoxypyridinoline, PTH, areal BMD (aBMD), calcaneal quantitative ultrasound
(QUS), and physical performance were assessed at baseline. Fractures and
mortality were recorded during a mean follow-up of 7.0 years. RESULTS: Bone
marker levels were higher in women with Hcy in the highest quartile compared with
all other women (p < 0.05). The most evident correlation between Hcy and a bone
marker was seen with CTX (r = 0.19, p < 0.001). aBMD (hip) was 4% lower, QUS was
up to 2% lower, and gait speed was 11% slower among women with Hcy in the highest
quartile compared with the other women (p < 0.05). During the follow-up, 267
women sustained at least one low-energy fracture (including 69 hip fractures).
When women in the highest Hcy quartile were compared with all other women, the
hazard ratios (HRs) for sustaining any type of fracture was 1.18 (95% CI, 0.89
1.36) and for hip fracture was 1.50 (95% CI, 0.91-1.94). For the same group of
women, the mortality risk was 2.16 (95% CI, 1.58-2.55). Adjustments for
confounders did not substantially change these associations. Adjustment for PTH
increased the HR for hip fracture to 1.67 (95% CI, 1.01-2.17). Low vitamin B(12)
or folate was not associated with increased fracture risk or mortality.
CONCLUSIONS: High Hcy levels were associated with higher bone turnover, poor
physical performance, and lower BMD. There was no clear association to fracture
risk. The increased mortality among women with high Hcy levels indicates that a
high Hcy level may be a marker of frailty.
PMID- 17032147
TI - TGF-beta promotes the establishment of renal cell carcinoma bone metastasis.
AB - Bone metastases develop in approximately 30% of patients with RCC, and the
mechanisms responsible for this phenomenon are unknown. We found that TGF-beta1
stimulation of RCC bone metastasis cells promotes tumor growth and bone
destruction possibly by stimulating paracrine interactions between tumor cells
and the bone. INTRODUCTION: Bone metastasis is a frequent complication and causes
marked morbidity in patients with renal cell carcinoma (RCC). Surprisingly, the
specific mechanisms of RCC interaction with bone have been scarcely studied
despite the inability to prevent or effectively treat bone metastasis. Bone is a
reservoir for various growth factors including the pleiotropic cytokine TGF
beta1. TGF-beta1 has been shown to have tumor-supportive effects on advanced
cancers and evidence suggests its involvement in promoting the development of
breast cancer bone metastasis. Here, we studied the potential role of TGF-beta1
in the growth of RCC bone metastasis (RBM). MATERIALS AND METHODS: To inhibit TGF
beta1 signaling, RBM cells stably expressing a dominant-negative (DN) TGF-betaRII
cDNA were generated. The in vivo effect of TGF-beta1 on RBM tumor growth and
osteolysis was determined by histological and radiographic analysis,
respectively, of athymic nude mice after intratibial injection of parental, empty
vector, or DN RBM cells. The in vitro effect of TGF-beta1 on RBM cell growth was
determined after TGF-beta1 treatment by MTT assay. RESULTS: TGF-beta1 and the TGF
beta receptors I and II (TGF-betaRI/II) were consistently expressed in both RBM
tissues and cell lines. Inhibition of TGF-beta1 signaling in RBM cells
significantly reduced tumor establishment and osteolysis observed in vivo after
injection into the murine tibia, although no effect on tumor establishment was
observed after injection of RBM cells subcutaneously or into the renal
subcapsule. Treatment of five RBM cell lines with TGF-beta1 in vitro either had
no effect (2/5) or resulted in a significant inhibition (3/5) of cell growth,
suggesting that TGF-beta1 may promote RBM tumor growth indirectly in vivo.
CONCLUSIONS: TGF-beta1 stimulation of RBM cells plays a role in promoting tumor
growth and subsequent osteolysis in vivo, likely through the initiation of tumor
promoting paracrine interactions between tumor cells and the bone
microenvironment. These data suggest that inhibition of TGF-beta1 signaling may
be useful in the treatment of RBM.
PMID- 17032148
TI - Long-term control of bone turnover in Paget's disease with zoledronic acid and
risedronate.
AB - A single 5-mg infusion of zoledronic acid restores biochemical markers of bone
turnover into the reference range in the majority of patients with Paget's
disease and maintains biochemical remission for at least 2 years. This effect is
largely independent of pretreatment disease activity and prior bisphosphonate
therapy. INTRODUCTION: Zoledronic acid (ZOL) is a potent bisphosphonate that
produces a rapid and complete control of the increased bone turnover of Paget's
disease. Long-term control of disease activity is an important aim of treatment
in the hope that this will reduce the risk of complications such as deformity,
fracture, and degenerative joint disease. MATERIALS AND METHODS: This study
compares the ability of ZOL 5 mg given as a 15-minute intravenous infusion with
risedronate (RIS) 30 mg daily by mouth for 60 days to maintain long-term control
of bone turnover. No bisphosphonate was given during the extension study. All
patients (n = 296) who achieved a therapeutic response, defined as normalization
or a >75% reduction in the total alkaline phosphatase (total ALP) excess above
the midpoint of the reference range, were eligible for inclusion. RESULTS: ZOL
maintained the mean level of total ALP at the middle of the reference range,
whereas those treated with risedronate showed a linear increase in total ALP from
the 6-month post-treatment time-point. Both treatments resulted in a linear
relationship between the 6-month nadir and 24-month total ALP. The relationship
for RIS was shifted upward, showing that for a given level of post-treatment
biochemical activity, bone turnover increased with time. This was in contrast to
the ZOL-treated patients where total ALP generally remained unchanged over this
18-month extension period. A similar pattern of response was seen with the other
bone turnover markers. CONCLUSIONS: ZOL maintains bone turnover within the
reference range over 24 months from the initiation of treatment. A reduction in
the incidence and severity of long-term complications may require persistent
normalization of bone turnover over many years, and this now seems a realistic
possibility with ZOL.
PMID- 17032149
TI - Effect of enzyme replacement therapy with imiglucerase on BMD in type 1 Gaucher
disease.
AB - The effect of ERT with imiglucerase on BMD in type 1 GD was studied using BMD
data from the International Collaborative Gaucher Group Gaucher Registry. Data
were analyzed for 160 untreated patients and 342 ERT-treated patients.
Imiglucerase significantly improves BMD in patients with GD, with 8 years of ERT
leading to normal BMD. INTRODUCTION: The objective was to determine the effect of
enzyme replacement therapy (ERT; Cerezyme, imiglucerase) on BMD in type 1 Gaucher
disease (GD). MATERIALS AND METHODS: The study population included all adults
(men, 18-70 years; women, 18-50 years) enrolled in the International
Collaborative Gaucher Group (ICGG) Gaucher Registry for whom lumbar spine BMD
measurements were available. BMD data with up to 8 years of follow-up were
analyzed for 160 patients who received no ERT and 342 patients treated with ERT
alone. BMD was assessed by DXA of the lumbar spine. Z scores for patients with GD
were compared with a reference population. From the model's estimate, percent of
patients by age and sex with osteoporosis (T score < or = -2.5) were calculated.
RESULTS: DXA Z scores for patients with GD in the no ERT (untreated) group were
significantly below normal (y intercept = -0.80 Z score units, p < 0.001) and
remained approximately 1 SD below the reference population over time (slope =
0.010 Z score units per year, p = 0.68). The DXA Z scores for patients with GD
who received ERT at a dose of 60 U/kg/2 weeks were significantly lower than the
reference population at baseline (y-intercept = -1.17 Z score units, p < 0.001),
but improved significantly over time (slope = +0.132 Z score units per year, p <
0.001). A significant dose-response relationship was noted for the ERT group,
with the slopes for the three main dosing groups of 15, 30, and 60 U/kg/2 weeks
of +0.064, +0.086, and +0.132 Z score units per year, respectively. The BMD of
patients with GD treated with ERT increased to -0.12 (60 U/kg/2 weeks), -0.48 (30
U/kg/2 weeks), and -0.66 (15 U/kg/2 weeks) SD of the mean of the reference
population after 8 years of ERT, approaching the reference population. Estimated
risk of osteoporosis of this GD population, if left untreated, ranged from
approximately 10 to 30% in women and 10% to 25% in men. CONCLUSIONS: ERT with
imiglucerase (Cerezyme) may increase BMD in patients with GD. Response to
treatment with imiglucerase is slower for BMD than for hematologic and visceral
aspects of GD. A normal (age- and sex-adjusted) BMD should be a therapeutic goal
for patients with type 1 GD.
PMID- 17032150
TI - Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on
BMP-stimulated bone formation.
AB - Sclerostin is an osteocyte-derived negative regulator of bone formation. It
inhibits BMP-stimulated bone formation both in vitro and in vivo but has no
direct effect on BMP signaling. Instead, sclerostin inhibits Wnt signaling that
is required for BMP-stimulated osteoblastic differentiation. INTRODUCTION:
Sclerostin is a member of the Dan family of glycoproteins of which many members
have been reported to antagonize BMP activity. Sclerostin has been shown to
inhibit BMP-stimulated bone formation, but its mechanism of action seems to be
different from classical BMP antagonists. In this study, we investigated the
mechanism by which sclerostin inhibits BMP-stimulated bone formation. MATERIALS
AND METHODS: DNA electroporation of calf muscle of mice using expression plasmids
for BMP and sclerostin was used to study the effect of sclerostin on BMP-induced
bone formation in vivo. Transcriptional profiling using microarrays of
osteoblastic cells treated with BMP in the absence or presence of sclerostin was
used to find specific growth factor signaling pathways affected by sclerostin.
The affected pathways were further studied using growth factor-specific reporter
constructs. RESULTS: BMP-induced ectopic bone formation in calf muscle of mice
was prevented by co-expression of sclerostin in vivo. Transcriptional profiling
analysis of osteoblastic cultures indicated that sclerostin specifically affects
BMP and Wnt signaling out of many other growth signaling pathways. Sclerostin,
however, did not inhibit stimulation of direct BMP target genes. Furthermore, we
did not obtain any evidence for sclerostin acting as a direct BMP antagonist
using a BMP-specific reporter construct. In contrast, sclerostin shared many
characteristics with the Wnt antagonist dickkopf-1 in antagonizing BMP-stimulated
bone formation and BMP- and Wnt-induced Wnt reporter construct activation.
CONCLUSIONS: Sclerostin inhibits BMP-stimulated bone formation but does not
affect BMP signaling. Instead, it antagonizes Wnt signaling in osteoblastic
cells. High bone mass in sclerosteosis and van Buchem disease may, therefore,
result from increased Wnt signaling.
PMID- 17032151
TI - Development of oncolytic adenovirus armed with a fusion of soluble transforming
growth factor-beta receptor II and human immunoglobulin Fc for breast cancer
therapy.
AB - We have developed an approach to cancer gene therapy in which the oncolytic
effects of an adenoviral vector have been combined with selective expression of a
soluble form of transforming growth factor (TGF)-beta receptor II fused with Fc
(sTGFbetaRIIFc). We chose to use adenoviral dl01/07 mutant because it can
replicate in all cancer cells regardless of their genetic defects. An oncolytic
adenovirus expressing sTGFbetaRIIFc (Ad.sT- betaRFc) was constructed by
homologous recombination. Infection of MDA-MB-231 and MCF-7 human breast cancer
cells with Ad.sTbetaRFc produced sTGFbetaRIIFc, which was released into the
media. The conditioned media containing sTGFbetaRIIFc could bind with TGF-beta 1
and inhibited TGF-beta-dependent transcription in target cells. Infection of MDA
MB-231, MCF-7, and 76NE human breast cancer cells with Ad.sTbetaRFc resulted in
high levels of viral replication, comparable to that of a wild-type dl309 virus.
Although some viral replication was observed in actively dividing normal human
lung fibroblasts, there was no replication in nonproliferating normal cells.
Direct injection of Ad.sTbetaRFc into MDA-MB-231 human breast xenograft tumors
grown in nude mice resulted in a significant inhibition of tumor growth, causing
tumor regression in more than 85% of the animals. These results indicate that it
is possible to construct an oncolytic virus expressing sTGFbetaRIIFc in which
both viral replication and transgene expression remain intact, and the
recombinant adenovirus is oncolytic in a human tumor xenograft model. On the
basis of these results we believe that it may be feasible to develop a cancer
gene therapy approach using Ad.sTbetaRFc as an antitumor agent.
PMID- 17032152
TI - DNA vaccines: recent developments and future possibilities.
AB - The field of DNA vaccines continues to advance and several new strategies to
augment the immunogenicity of DNA vaccines are under evaluation. The majority of
these studies are in the early preclinical stage, but some DNA vaccines have
moved into clinical trials. In this review, we describe some of the more recent
efforts aimed at increasing the immunogenicity of DNA vaccines, including the use
of genetic adjuvants and plasmid-based expression of viral replicons. In
addition, we discuss the possibility of using DNA vaccines to address emerging
infectious agents where they may provide an advantage over other vaccine
strategies and we review some areas where DNA vaccines have been used to target
self-antigens.
PMID- 17032153
TI - Recent developments in the application of plasmid DNA-based vectors and small
interfering RNA therapeutics for cancer.
AB - Increased understanding of the molecular pathological mechanisms of cancer, the
advent of novel molecular tools such as synthetic small interfering RNA (siRNA)
or plasmid DNA-based vectors (pDNA), and technology for the in vivo delivery of
such biomolecular therapeutics have provided an encouraging perspective for
cancer therapy. Numerous pDNAs and siRNAs have been tested in preclinical cancer
models, and these first approaches have reached clinical evaluation. The
therapeutic effector mechanisms include interference with neoangiogenesis,
blockage of cell division, promotion of apoptosis and sensitization to
chemotherapy, delivery of cytotoxic genes, and activation of anticancer immune
responses. Physical methods have been developed for highly effective regional
delivery. A series of innovative "smart" formulations directs the current
development toward safe and effective systemic tumor-targeted delivery of pDNA
and siRNA.
PMID- 17032154
TI - Regulation of gene therapy in china.
PMID- 17032155
TI - Targeting gene therapy for prostate cancer cells by liposomes complexed with anti
prostate-specific membrane antigen monoclonal antibody.
AB - Prostate-specific membrane antigen (PSMA) is a membrane-bound antigen expressed
on the surface of prostate cancer cells, and this paper describes the use of an
antibody against PSMA for targeting gene therapy. We coupled anti-PSMA monoclonal
antibody with poly-L-lysine and then incubated it with plasmids. These complexes
were then transfected with cationic liposomes into cells. The transfection
efficiency of anti-PSMA- liposome complex was higher than that of normal IgG
liposome complex in PSMA-positive LNCaP cells. Furthermore, anti-PSMA-liposome
complex containing a suicide gene, thymidine kinase, demonstrated a selective
growth-inhibitory effect on LNCaP cells in vitro, but did not exert a significant
effect on PSMA-negative cells. In an in vivo xenograft model of LNCaP cells in
nu/nu mice, we administered the complexes via the tail vein. Judging on the basis
of both 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining and
luciferase assay findings, a significant enrichment of plasmid DNA was observed
in LNCaP xenografts with anti-PSMA-liposome complex in comparison with normal IgG
liposome complex. However, the distribution of plasmid DNA did not change
substantially in any other organs including the liver, kidney, lung, and spleen.
Moreover, in suicide gene therapy, anti-PSMA-liposome complex exerted a
significant inhibitory effect on the growth of LNCaP xenograft, in contrast to
normal IgG-liposome complex.
PMID- 17032157
TI - A randomized controlled trial of cognitive behavior therapy for borderline
personality disorder: rationale for trial, method, and description of sample.
AB - This paper describes the rationale for a randomized controlled trial, comparing
cognitive behavior therapy in addition to treatment as usual with treatment as
usual alone, for borderline personality disorder. Previous pioneering randomized
controlled trials of psychotherapies have suffered from methodological weaknesses
and have not always been reported clearly to allow adequate evaluation of either
the individual study or comparisons across studies to be undertaken. We report on
the recruitment and randomization, design, and conduct of an ongoing randomized
controlled trial of one hundred and six patients with borderline personality
disorder. Primary and secondary hypotheses and their planned analyses are stated.
The baseline characteristics of 106 patients meeting diagnostic criteria for
borderline personality disorder are described.
PMID- 17032158
TI - The effectiveness of cognitive behavior therapy for borderline personality
disorder: results from the borderline personality disorder study of cognitive
therapy (BOSCOT) trial.
AB - The outcome of a randomized controlled trial of cognitive behavior therapy in
addition to treatment as usual (CBT plus TAU) compared with TAU alone (TAU) in
one hundred and six participants meeting diagnostic criteria for borderline
personality disorder is described. We anticipated that CBT plus TAU would
decrease the number of participants with in-patient psychiatric hospitalizations
or accident and emergency room contact or suicidal acts over twelve months
treatment and twelve months follow-up, compared with TAU. We also anticipated
that CBT plus TAU would lead to improvement in a range of secondary outcomes of
mental health and social functioning compared to TAU. Of the 106 participants
randomized, follow-up data on 102 (96%) was obtained at two years. Those
randomized to CBT were offered an average of 27 sessions over 12 months and
attended on average 16 (range 0 to 35). We found that the global odds ratio of a
participant in the CBT plus TAU group compared with the TAU alone group having
any of the outcomes of a suicidal act, in-patient hospitalization, or accident
and emergency contact in the 24 months following randomization was 0.86 (95%
confidence interval [CI] 0.45 to 1.66, p = 0.66). The corresponding global odds
ratio, excluding accident and emergency room contact, was 0.75 (95% CI 0.37 to
1.54, p = 0.44). In terms of the number of suicidal acts, there was a significant
reduction over the two years in favor of CBT plus TAU over TAU, with a mean
difference of -0.91 (95% CI -1.67 to -0.15, p = 0.020). Across both treatment
arms there was gradual and sustained improvement in both primary and secondary
outcomes, with evidence of benefit for the addition of CBT on the positive
symptom distress index at one year, and on state anxiety, dysfunctional beliefs
and the quantity of suicidal acts at two year follow-up. CBT can deliver
clinically important changes in relatively few clinical sessions in real clinical
settings.
PMID- 17032159
TI - The cost-effectiveness of cognitive behavior therapy for borderline personality
disorder: results from the BOSCOT trial.
AB - Borderline personality disorder places a significant burden on healthcare
providers and other agencies. This study evaluated the cost-effectiveness of
cognitive behavior therapy plus treatment as usual compared to treatment as usual
alone for patients with borderline personality disorder. The economic analysis
was conducted alongside a multi-center, randomized controlled trial. The costs of
primary and secondary healthcare utilization, alongside the wider economic costs,
were estimated from medical records and patient self-report. The primary outcome
measure used was the quality-adjusted life year (QALY), assessed using EuroQol.
On average, total costs per patient in the cognitive behavior therapy group were
lower than patients receiving usual care alone (-689 pounds sterling), although
this group also reported a lower quality of life (-0.11 QALYs). These differences
were small and did not approach conventional levels of statistical significance.
The use of cognitive therapy for borderline personality disorder does not appear
to demonstrate any significant cost-effective advantage based on the results of
this study.
PMID- 17032160
TI - Manual assisted cognitive treatment for deliberate self-harm in borderline
personality disorder patients.
AB - This study examines the efficacy of a short-term individual therapy, Manual
Assisted Cognitive Treatment (MACT), which was developed to treat parasuicidal
(suicidal or self-harming) patients. In this trial, MACT was modified to focus on
deliberate self-harm (DSH) in patients with borderline personality disorder
(BPD). Thirty BPD patients who were engaged in DSH while in ongoing treatments,
i.e., treatment-as-usual (TAU), were randomly assigned to receive MACT (N = 15)
or not. DSH and level of suicide ideation were assessed at the baseline, at
completion of the MACT intervention, and six months later. Results indicated that
MACT was associated with significantly less frequent DSH upon completion of the
intervention and with significantly decreased DSH frequency and severity at the
six months follow-up. Moreover, MACT's contribution to reducing DSH frequency and
severity was greater than the contribution by the amount of concurrent
treatments. In contrast, MACT did not affect the level of suicide ideation and
time-to-repeat of DSH. In conclusion, MACT seems to be a promising intervention
for DSH in patients with BPD. More definitive studies are needed.
PMID- 17032161
TI - Six-year follow-up of three treatment programs to personality disorder.
AB - Previous studies of long-term outcome for personality disorder (PD) were either
retrospective in design or did not include a control condition. In this paper we
report results for three PD cohorts (N = 111) treated in two different specialist
psychosocial programs (step-down and long-term inpatient) and in general
psychiatric treatment as usual (TAU), which were prospectively followed up for 72
months after intake. The three PD samples were compared on symptom severity,
social adjustment, global functioning and other clinical indicators (self
mutilation, parasuicide and readmission rates) at intake, 6, 12, 24, and 72
months. Results indicated that a specialist step-down model showed significantly
greater change than a purely inpatient model and TAU in most key dimensions of
functioning, a difference maintained at 72-months follow-up. Improvement in the
samples was not associated with amount of intercurrent treatment received in the
year prior to the follow-up assessment. This study confirms that a step-down
program retains significant improvement associated with a specialist psychosocial
approach for PD. However, this conclusion should be qualified by design
limitations. The samples were not randomly allocated to the three conditions and
the naturalistic geographical allocation used in the study created a potential
for a number of confounds. Whilst we used extensive statistical controls, the
possibility that the differences found between the groups may be due to
population differences cannot be discounted.
PMID- 17032162
TI - Relative impact of young adult personality disorders on subsequent quality of
life: findings of a community-based longitudinal study.
AB - Little is known about long-term prognostic implications of personality disorder
(PD) for quality of life (QOL) in the young adult population not selected for
psychiatric treatment. The purpose of this study was to determine the association
of PDs with QOL assessed after an 11-year interval. PDs were assessed in 1991
1994 at mean age 22, and indicators of QOL were assessed in 2001-2004 at mean age
33 based on a community sample of 588 young adults. Findings indicated that any
PD, or a cluster A, B, or C PD each were independently associated with elevated
impairment in overall QOL after adjusting for demographic variables, co-occurring
Axis I disorder, and physical illness, and PDs in other clusters. Cluster B PD
had a greatest adverse impact on QOL. Symptoms of antisocial, borderline, and
schizotypal PD symptoms were independently associated with significant reductions
in QOL; avoidant, paranoid, and dependent PD symptoms were associated with
smaller reductions, not reaching statistical significance. Symptoms of other
individual PDs were not associated with reduced QOL. PDs in young adults in the
community have an enduring and adverse impact on subsequent QOL that cannot be
attributed to physical illness or Axis I psychiatric disorder.
PMID- 17032163
TI - Is the appendix a useful appendage? An empirical examination of depressive,
passive-aggressive (negativistic), sadistic, and self-defeating personality
disorders.
AB - Decisions about whether to include depressive, passive-aggressive, sadistic, and
self-defeating disorders in Axis II have been made difficult by a relative dearth
of data. We report the results of a study identifying potential defining features
of these diagnoses and assessing their distinctiveness from other Axis II
personality disorders (PDs). A national sample of experienced psychiatrists and
psychologists used the SWAP-200 to describe a patient with a current axis II
disorder or an appendix or deleted PD from DSM-II-R. We examined clinicians'
descriptions of patients to identify their most characteristic features, and then
applied an empirical clustering procedure, Q-factor analysis, to see whether
versions of these disorders would emerge empirically. As currently
conceptualized, only passive-aggressive PD was distinct from other PDs. When the
data were subjected to Q-factor analysis, the first and largest grouping was a
dysphoric (depressive) PD. A hostile-negativistic subcategory emerged that
resembled passive-aggressive PD, along with a revised dependent diagnosis that
included many self-defeating/masochistic features. The results suggest that a
depressive or dysphoric personality may represent an internalizing spectrum of
personality pathology, and that a hostile-negativistic PD may be distinct from
the disorders in the text of DSM-IV. Sadistic and self-defeating PD do not appear
to represent distinct disorders, although they include personality traits (sadism
and revictimization) associated with distinct developmental histories.
PMID- 17032164
TI - Mx1 and IP-10: biomarkers to measure IFN-beta activity in mice following gene
based delivery.
AB - Recombinant interferon-beta (IFN-beta) protein is used successfully for the
treatment of multiple sclerosis (MS). Gene therapy might be an alternative
approach to overcome drawbacks occurring with IFN-beta protein therapy. A
critical issue in developing a new approach is detection of biologically active
IFN-beta in preclinical models. The goal of the present study was to determine if
Mx1 and IP-10, which are known to be activated after IFN-beta treatment in
humans, can be used as biomarkers in mice. In three in vivo experiments, the
correlation between different methods of murine IFN-beta (MuIFN-beta) delivery
and biomarker induction was studied: (1) bolus protein delivery by intravenous
(i.v.) or intramuscular (i.m.) injection, (2) gene-based delivery of IFN- beta by
i.m. injection of plasmid DNA, followed by electroporation, and (3) gene-based
delivery of IFN-beta by i.m. injection of adenovirus-associated type 1 (AAV1).
Short-term induction of Mx1 mRNA and IP-10 was observed after treatment with
bolus MuIFN-beta protein. Long-term induction of both biomarkers was observed
after IFN-beta plasmid DNA delivery or when AAV1 was used as the vector. The
experiments demonstrate that gene-based delivery provides sustained levels of IFN
beta compared with bolus protein injection and that Mx1 RNA and IP-10 can be used
to monitor biologically active circulating plasma MuIFN-beta protein in mice.
PMID- 17032165
TI - The proinflammatory cytokine interleukin-18 alters multiple signaling pathways to
inhibit natural killer cell death.
AB - The proinflammatory cytokine, interleukin-18 (IL-18), is a natural killer (NK)
cell activator that induces NK cell cytotoxicity and interferon-gamma (IFN-gamma)
expression. In this report, we define a novel role for IL-18 as an NK cell
protective agent. Specifically, IL-18 prevents NK cell death initiated by
different and distinct stress mechanisms. IL-18 reduces NK cell self-destruction
during NK-targeted cell killing, and in the presence of staurosporin, a potent
apoptotic inducer, IL-18 reduces caspase-3 activity. The critical regulatory step
in this process is downstream of the mitochondrion and involves reduced cleavage
and activation of caspase-9 and caspase-3. The ability of IL-18 to regulate cell
survival is not limited to a caspase death pathway in that IL-18 augments tumor
necrosis factor (TNF) signaling, resulting in increased and prolonged mRNA
expression of c-apoptosis inhibitor 2 (cIAP2), a prosurvival factor and caspase-3
inhibitor, and TNF receptor-associated factor 1 (TRAF1), a prosurvival protein.
The cumulative effects of IL-18 define a novel role for this cytokine as a
molecular survival switch that functions to both decrease cell death through
inhibition of the mitochondrial apoptotic pathway and enhance TNF induction of
prosurvival factors.
PMID- 17032166
TI - MKK3/6-p38 MAPK signaling is required for IL-1beta and TNF-alpha-induced RANKL
expression in bone marrow stromal cells.
AB - Coupled bone turnover is directed by the expression of receptor-activated NF
kappaB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG).
Proinflammatory cytokines, such as interleukin-1beta (IL-1beta) and tumor
necrosis factor-alpha (TNF-alpha) induce RANKL expression in bone marrow stromal
cells. Here, we report that IL-1beta and TNF-alpha-induced RANKL requires p38
mitogen-activating protein kinase (MAPK) pathway activation for maximal
expression. Real-time PCR was used to assess the p38 contribution toward IL-1beta
and TNF-alpha-induced RANKL mRNA expression. Steady-state RANKL RNA levels were
increased approximately 17-fold by IL-1beta treatment and subsequently reduced
approximately 70%-90% when p38 MAPK was inhibited with SB203580. RANKL mRNA
stability data indicated that p38 MAPK did not alter the rate of mRNA decay in IL
1beta-induced cells. Using a RANKL-luciferase cell line receptor containing a 120
kB segment of the 5' flanking region of the RANKL gene, reporter expression was
stimulated 4-5-fold by IL-1beta or TNF-alpha treatment. IL-1beta-induced RANKL
reporter expression was completely blocked with specific p38 inhibitors as well
as dominant negative mutant constructs of MAPK kinase-3 and -6. In addition,
blocking p38 signaling in bone marrow stromal cells partially inhibited IL-1beta
and TNF-alpha-induced osteoclastogenesis in vitro. Results from these studies
indicate that p38 MAPK is a major signaling pathway involved in IL-1beta and TNF
alpha-induced RANKL expression in bone marrow stromal cells.
PMID- 17032167
TI - Modulation of immune responses induced by DNA vaccine expressing glycoprotein B
of Pseudorabies Virus via coadministration of IFN-gamma-associated cytokines.
AB - The immunomodulatory efficacy of interferon-gamma (IFN-gamma)-associated
cytokines coadministered with a plasmid DNA vaccine has been investigated, with
variable results. Therefore, to test the immunomodulatory effect of IFN-gamma
associated cytokines as vaccine adjuvant, the present study evaluated the immune
responses induced by pseudorabies virus (PrV) gB-encoded plasmid DNA vaccine
coadministered with IFN-gamma-associated cytokines and chemokines. These
cytokines and chemokines included interleukin-12 (IL-12) and IL-18, as potent
inducers of IFN-gamma, and IFN-gamma-inducible protein (IP-10), the production of
which is IFN-gamma dependent. A coinjection of either IL-12 or IL-18 strongly
suppressed the humoral antibody responses but increased the production of the Th1
type cytokines IFN-gamma and IL-2 from immune T cells. Such antibody suppression
was closely related to the increased susceptibility against a virulent viral
challenge. On the other hand, IP-10 exhibited enhanced immune responses in both
antibody responses and IFN-gamma production of immune T cells and facilitated the
prolonged survival of infected mice. In contrast, there was no significant change
in the immune responses of the mice that received codelivery of IFN-gamma.
Therefore, IFN-gamma-associated cytokines, as Th1-type inducers, can generate
unexpected and unwanted effects, and their application as a vaccine adjuvant
should be carefully evaluated depending on the target antigens.
PMID- 17032168
TI - A role for Stat1 in the regulation of lipopolysaccharide-induced interleukin
1beta expression.
AB - Because the induction of interleukin-1beta (IL-1beta) is critical to
antibacterial host defenses and its excessive generation is a prominent component
of sepsis, regulation of this proinflammatory cytokine is a critical factor in
the immune response to lipopolysaccharide (LPS). We previously showed that LPS
induced IL-1beta expression was regulated by a Stat1-dependent, nitric oxide (NO)
mediated mechanism. Subsequent in vivo studies showed that whereas Stat1 had a
role in the downregulation of IL-1beta expression, it had a more significant
effect on its initial induction. Although both interferon-beta (IFN-beta) and IFN
gamma activate Stat1, the early appearance of IFN-beta in the circulation after
LPS administration suggested its pivotal role in Stat1-mediated IL-1beta
expression in vivo. Further in vitro analysis of peritoneal macrophages from IFN
beta (/), Stat1(/), and caspase-1(/) mice and their wild-type controls following
LPS stimulation demonstrated that IL-1beta mRNA was expressed in these mice but
not in macrophages from MyD88(/) mice. Despite the presence of IL-1beta mRNA, IL
1beta protein was markedly reduced in the absence of Stat1 activation in
macrophages derived from IFN-beta (/) and Stat1(/) mice or in the absence of
caspase-1 activity, which itself was dependent on Stat1 activation. These studies
support the hypothesis that the expression of IL-1beta requires both the MyD88
dependent induction of IL-1beta mRNA and pro-IL-1beta as well as the MyD88
independent, Stat1-mediated processing of that gene product into active cytokine.
PMID- 17032169
TI - Attenuation of cytokine responsiveness during T cell development and
differentiation.
AB - Cytokines play critical roles during T cell development; however, it is unclear
to what extent development is altered by the high levels of cytokines produced
during immune responses. A potential mechanism to shield developing cells from
cytokine influence is attenuation of cytokine signaling. Using intracellular
staining and flow cytometry to detect cytokine-induced Stat phosphorylation, we
analyzed the cytokine responsiveness of developmentally defined mouse T cells. We
assessed CD4(-)CD8(-) (DN), CD4(+)CD8(+) (DP), CD4(+)CD8(-) (SP4), and CD4(
)CD8(+) (SP8) in the thymus, and CD4(+)CD44(lo) (naive), CD4(+)CD44(hi) (memory),
CD8(+)CD44(lo) (naive), and CD8(+)CD44(hi) (memory) in the periphery for
responsiveness to interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL- 10, IL-15,
interferon-alpha (IFN-alpha), and IFN-gamma. SP thymocytes responded to a wider
range of cytokines than did the less mature DN and DP subpopulations. DP
thymocytes were nonresponsive to all cytokines tested except for modest responses
to IL-4 and IFN-alpha. Peripheral naive and memory T cells also displayed
differential cytokine sensitivity. Memory T cells were less responsive to the
proinflammatory cytokines IL-6 and IFN-gamma when compared with naive T cells,
and the memory CD4(+) subset was less responsive to IL-4. In summary, developing
thymocytes and memory T cells appear to be resistant to the influences of
numerous cytokines produced during immune responses.
PMID- 17032170
TI - Mechanism of direct hepatotoxic effect of KC chemokine: sequential activation of
gene expression and progression from inflammation to necrosis.
AB - This work aimed to show that an important, yet unrecognized, role of KC chemokine
in the liver is regulation of gene expression. KC expression in the liver
stimulated three classes of genes in this temporal order: immediate-early genes,
proinflammatory genes, and profibrotic genes. Transcription factors E2F5 and
early growth response 1 (EGR1), Ca(2+) signaling molecules S100A8 and S100A9, and
two oxidative stress-induced genes were identified as immediate-early genes of
KC. Expression of these genes was stimulated at 3-5-fold increased KC
concentrations. Expression of proinflammatory genes was activated 6 h after the
immediateearly genes, and they included interleukin-1alpha (IL-1alpha) and IL
1beta. KC receptor gene CXCR2 was also upregulated, suggesting that KC may act
through a positive feedback loop. Stimulation of expression of profibrotic genes,
including type I collagen, was seen only after the proinflammatory genes were
highly expressed for 12 h. KC is a potent regulator of gene expression that
proceeds in a sequential manner. Immediate-early genes of KC stimulation were
identified. The positive feedback regulation and an increased oxidative stress
induced by KC may explain the poor prognosis in liver patients with elevated
levels of CXC chemokines.
PMID- 17032171
TI - Intestinal permeability and cytokine inflammatory response in multiply injured
patients.
AB - In experimental settings, the increased intestinal permeability (IP) following
severe trauma is associated with increased serum concentrations of cytokines.
Multiply injured patients are susceptible to the development of multiple organ
failure (MOF). The aim of this study was to determine if altered IP after trauma
was associated with upregulation of cytokines and if cytokines and IP influenced
the development of MOF. In 30 multiply injured patients, IP was measured on days
2 and 4 after injury using the lactulose-mannitol (L-M) test, and the levels of
tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8 were
determined simultaneously. The L-M ratio increased significantly from 0.049
(0.017-0.133) on day 2 to 0.150 (0.059-0.339) on day 4 (p < 0.02) On day 4, a
significant correlation was also found between the L-M ratio and IL-6 (r = 0.43,
p < 0.03). The IL-6 level on days 2 and 4 was significantly (p < 0.01 and p <
0.03, respectively) higher in MOF patients than in those without MOF, as was the
TNF-alpha level on day 4 significantly higher (p < 0.04) in MOF patients. IP
increases following multiple trauma, and on day 4 it correlates with the IL-6
level. However, in patients who develop MOF only cytokines are invariably
increased, with IL-6 alone being significantly increased on both measurements in
these patients.
PMID- 17032173
TI - A physiological role of AMP-activated protein kinase in phenobarbital-mediated
constitutive androstane receptor activation and CYP2B induction.
AB - CAR (constitutive androstane receptor) is a nuclear receptor that regulates the
transcription of target genes, including CYP (cytochrome P450) 2B and 3A. The
transactivation by CAR is regulated by its subcellular localization; however, the
mechanism that governs nuclear translocation has yet to be clarified. It has been
reported recently that AMPK (AMP-activated protein kinase) is involved in
phenobarbital-mediated CYP2B induction in a particular culture system. We
therefore investigated in vivo whether AMPK is involved in the activation of CAR
dependent gene expression. Immunoblot analysis using an antibody which recognizes
Thr-172-phosphorylated AMPKalpha1/2 revealed phenobarbital-induced AMPK
activation in rat and mouse livers as well. Phenobarbital, however, failed to
increase the liver phospho-AMPK level of tumour-bearing rats in which CAR nuclear
translocation had been impaired. In in vivo reporter gene assays employing PBREM
(phenobarbital-responsive enhancer module) from CYP2B1, an AMPK inhibitor 8-bromo
AMP abolished phenobarbital-induced transactivation. In addition, Cyp2b10 gene
expression was attenuated by 8-bromo-AMP. Forced expression of a dominant
negative mutant and the wild-type of AMPKalpha2 in the mouse liver suppressed and
further enhanced phenobarbital-induced PBREM-reporter activity respectively.
Moreover, the AMPK activator AICAR (5-amino-4-imidazolecarboxamide riboside)
induced PBREM transactivation and an accumulation of CAR in the nuclear fraction
of the mouse liver. However, AICAR and metformin, another AMPK activator, failed
to induce hepatic CYP2B in mice and rats. These observations suggest that AMPK is
at least partly involved in phenobarbital-originated signalling, but the kinase
activation by itself is not sufficient for CYP2B induction in vivo.
PMID- 17032174
TI - Regulation of ceruloplasmin in human hepatic cells by redox active copper:
identification of a novel AP-1 site in the ceruloplasmin gene.
AB - Cp (ceruloplasmin), a copper containing plasma protein, mainly synthesized in the
liver, is known to be functional between the interface of iron and copper
metabolism. We have reported previously that Cp is regulated by cellular iron
status, but the process of the regulation of Cp by copper still remains a subject
for investigation. In the present paper, we show that PDTC (pyrrolidine
dithiocarbamate), a thiol compound widely known to increase intracellular redox
copper, regulates Cp expression in hepatic cells by a copper-dependent
transcriptional mechanism. To find out the mechanism of induction, chimeric
constructs of the Cp 5'-flanking region driving luciferase were transfected into
human hepatic cells. Deletion and mutational analyses showed the requirement of a
novel APRE [AP-1 (activator protein-1) responsive element] present about 3.7 kb
upstream of the translation initiation site. The role of AP-1 was confirmed by
electrophoretic mobility-shift analysis. Western blot and overexpression studies
detected the AP-1 as a heterodimer of c-jun and c-fos proteins. The activation of
AP-1 was found to be copper-dependent as a specific extracellular chelator
bathocuproine disulfonic acid blocked PDTC-mediated induction of AP-1-DNA binding
and increased reporter gene activity. Whereas, in a copper-free medium, PDTC
failed to activate either AP-1 or Cp synthesis, supplementation of copper could
reverse AP-1 activation and Cp synthesis. Our finding is not only the first
demonstration of regulation of Cp by redox copper but may also explain previous
findings of increased Cp expression in cancers like hepatocarcinoma, where the
intracellular copper level is higher in a redox compromised environment.
PMID- 17032175
TI - Positron emission tomography/computed tomography: diagnostic accuracy in
lymphoma.
AB - An accurate initial staging of patients with non-Hodgkin lymphoma (NHL) and
Hodgkin lymphoma (HL) is critical for the selection of an appropriate treatment.
Computed tomography (CT) remains the standard imaging technique, although it is
based on anatomic criteria. Positron emission tomography (PET) with 2-deoxy-2
[fluorine-18]fluoro-d-glucose (FDG) provides useful functional information but
requires anatomical correlation to localise lesions accurately. We have
prospectively compared the accuracy of combined PET/CT with that of CT and PET
alone at initial staging in lymphoma patients. Forty-seven newly diagnosed
patients were evaluated. PET/CT was superior compared with CT and PET in nodal
evaluation and detection of extranodal disease. Using a staging algorithm with
PET/CT resulted in the disease stage being increased in 11 of 47 patients (10 NHL
and 1 HL) (McNemar test P = 0.012). Therefore, a different treatment strategy
based on PET/CT findings was suggested for seven patients (14.8%). PET/CT
markedly improves accuracy in the diagnostic work-up of patients with lymphoma.
PMID- 17032176
TI - Outcome in patients with Wiskott-Aldrich syndrome following stem cell
transplantation: an analysis of 57 patients in Japan.
AB - A total of 57 patients with Wiskott-Aldrich syndrome (WAS) were studied after
undergoing stem cell transplantation (SCT) in Japan between January 1985 and
December 2004. Eleven patients received transplants from human leucocyte antigen
(HLA)-matched related donors, 10 from HLA-mismatched related donors, 21 from
unrelated bone marrow donors, and 15 from unrelated cord blood donors. Nine of
the 57 patients rejected the initial graft. The overall 5-year survival rate was
73.7% and the 5-year failure-free survival rate was 65.7% (failure was defined as
rejection or death). The overall 5-year survival rates for patients receiving
bone marrow and cord blood from unrelated donors were both 80.0%. Based on
univariate analysis, the factors associated with poor survival were:
transplantation from an HLA-mismatched related donor, patient age of more than 5
years at the time of transplantation, and a conditioning regimen other than
busulfan and cyclophosphamide (BU-CY) or busulfan, cyclophosphamide and
antithymocyte globulin (BU-CY-ATG). In a multivariate analysis, a conditioning
regimen other than BU-CY and BU-CY-ATG was the only independent factor associated
with transplantation failure. Given the improved outcome for WAS patients
following transplantation from an unrelated donor, we conclude that patients with
WAS should receive SCT as soon as possible after diagnosis.
PMID- 17032177
TI - Pure red cell aplasia associated with thymoma: clinical insights from a 50-year
single-institution experience.
AB - Acquired pure red cell aplasia (PRCA) is a rare disorder of erythropoiesis that
can develop in association with a thymoma. Optimal management of this subgroup is
unclear, and there have been few series reporting long-term clinical outcomes.
Here, we report features of 13 patients treated for PRCA associated with thymoma
over 50 years at our institution. Surgical resection of the thymoma was
insufficient for normalisation of erythropoiesis in all cases. T-cell gene
rearrangement studies did not routinely demonstrate a clonal process, and
ciclosporin and anti-thymocyte globulin were effective adjuvant treatments.
However, treatment-related morbidity was high, with frequent infectious
complications.
PMID- 17032178
TI - Pro: esophagectomy is the treatment of choice for high-grade dysplasia in
Barrett's esophagus.
PMID- 17032179
TI - CON: surgery for Barrett's with flat HGD-no!
PMID- 17032180
TI - A balancing view: an individualized approach to high-grade dysplasia is key:
esophagectomy, surveillance, or endoscopic therapy should all be considered.
PMID- 17032181
TI - Perils and pitfalls of small negative clinical trials.
PMID- 17032182
TI - Barrett's esophagus at a tertiary care center: association of age on incidence
and prevalence of dysplasia and adenocarcinoma.
AB - OBJECTIVES: Barrett's esophagus (BE) is traditionally thought of as a disease of
middle-aged Caucasian men. Little is known about BE in younger patients. We
sought to assess the effect of age on features of BE including the prevalence and
incidence of dysplasia and carcinoma. METHODS: All patients enrolled into the
Cleveland Clinic BE registry from 1979 to 2002 were studied. Age, ethnicity,
number of endoscopies, hiatal hernia size, length of Barrett's segment,
prevalence and incidence of dysplasia, and cancer were compared between patients
> or = 50 yr old and < 50 yr old. RESULTS: There were 837 patients in the
registry (638 > or = 50 yr, 199 < 50 yr). Hiatal hernia size was larger in
patients > or = 50 yr than in those < 50 yr (median 4.0 cm, interquartile range
2.0-5.0 cm vs 3.0, 2.0-4.0 cm; p < 0.01). Otherwise, there were no significant
differences among other features in the patient population. There were 225
patients with dysplasia or cancer (195 > or = 50 yr and 30 < 50 yr; p < 0.01). Of
this group, 176 were prevalent cases (159 > or = 50 yr and 17 < 50 yr) and 49
were incident cases (36 > or = 50 yr and 13 < 50 yr). The odds of those > or = 50
yr being a prevalent case of high-grade dysplasia or cancer was five times the
odds of those < 50 yr (p < 0.01). The incidence of dysplasia or cancer was
similar in both age groups. CONCLUSIONS: Our study supports emerging data that
approximately 25% of BE patients are less than 50 yr of age. While older patients
had a higher prevalence of dysplasia or adenocarcinoma, the incidence of
dysplasia and adenocarcinoma is similar in both age groups. Future screening
strategies for BE should recognize these important findings.
PMID- 17032183
TI - Predictors of endoscopic findings after Roux-en-Y gastric bypass.
AB - OBJECTIVES: To evaluate predictors of endoscopic findings in symptomatic patients
after Roux-en-Y gastric bypass (RYGBP) for obesity. METHODS: A retrospective
chart review of 1,001 RYGBP procedures was performed. Two hundred twenty-six
(23%) patients were identified as having endoscopy to evaluate upper
gastrointestinal symptoms following surgery. Polychotomous logistic regression
analysis was used to assess predictors of normal endoscopy, marginal ulcers,
stomal stenosis, and staple-line dehiscence. RESULTS: The most common endoscopic
findings were 99 (44%) normal postsurgical anatomy, 81 (36%) marginal ulcer, 29
(13%) stomal stenosis, and 8 (4%) staple-line dehiscence. Factors that
significantly increase the risk of marginal ulcers following surgery include
smoking (AOR = 30.6, 95% CI 6.4-146) and NSAID use (AOR = 11.5, 95% CI 4.8-28).
PPI therapy following surgery was protective against marginal ulcers (AOR = 0.33,
95% CI 0.11-0.97). Median time for diagnosis of marginal ulcers following surgery
was 2 months, and 77 of 81 (95%) presented within 12 months. CONCLUSIONS:
Following RYGBP surgery for obesity, smoking and NSAID use significantly increase
the risk of marginal ulceration, and PPI therapy is protective. Because a
significant majority of marginal ulcers present within 12 months of surgery, it
may be reasonable to consider prophylactic PPI therapy during this time period,
especially for high risk patients.
PMID- 17032184
TI - Stress ulcer prophylaxis in non-critically ill patients: less may be more.
AB - Significant upper gastrointestinal bleeding resulting from stress ulceration is a
serious life-threatening complication. However, it occurs relatively rarely even
in the sickest patients. Therefore, guidelines suggest that prophylaxis (e.g.,
with acid-suppressive therapy) should be reserved for highly selected patients.
Despite these recommendations, numerous studies suggest that many hospitalized
patients are inappropriately placed on acid-suppressive therapy (AST) for the
sole purpose of preventing stress ulceration. Moreover, it appears that once AST
is started, medications are continued even after discharge, resulting in further
unnecessary expenditure of resources. National and local efforts are needed to
curtail this practice that places patients at risk for drug side effects while
affording them little or no benefit.
PMID- 17032185
TI - Propofol alone titrated to deep sedation versus propofol in combination with
opioids and/or benzodiazepines and titrated to moderate sedation for colonoscopy.
AB - BACKGROUND: Propofol by nonanesthesiologists is controversial because the drug is
commonly used to produce deep sedation or general anesthesia. Propofol in
combination with opioids and/or benzodiazepines can be titrated to moderate
sedation, which might be safer. AIM: To compare recovery time, patient
satisfaction, and other end points with propofol alone titrated to deep sedation
versus propofol combination therapy with opioids and/or benzodiazepines. METHOD:
A randomized controlled clinical trial of propofol alone titrated to deep
sedation versus fentanyl plus propofol versus midazolam plus propofol versus
fentanyl plus midazolam plus propofol in 200 outpatients undergoing colonoscopy.
Each combination regimen was titrated to moderate sedation. RESULTS: Patients
receiving propofol alone received higher doses of propofol and had deeper
sedation scores compared with combination therapy (both p < 0.001). Patients
receiving combination regimens were discharged more quickly (median 13.0-14.7
versus 18.1 min) than those receiving propofol alone (p < 0.01). There were no
differences in vital signs or oxygen saturations among the study arms. There were
no significant differences in pain or satisfaction among the study arms in the
recovery area. At a follow-up phone call, patients receiving fentanyl and
propofol remembered more of the procedure than those in the other regimens (p <
0.005) and remembered more pain than those receiving propofol alone (p < 0.02).
CONCLUSIONS: Propofol in combination with fentanyl and/or midazolam can be
titrated to moderate levels of sedation without substantial loss of satisfaction
and with shorter recovery times compared with propofol titrated to deep sedation
throughout the procedure.
PMID- 17032186
TI - The impact of endoscopic ultrasound and computed tomography on the TNM staging of
early cancer in Barrett's esophagus.
AB - INTRODUCTION: Computed tomography (CT) and endoscopic ultrasound (EUS) are part
of the regular staging protocol in esophageal cancer. The value of the two
methods was assessed in patients with early cancer in Barrett's esophagus.
METHODS: One hundred consecutive patients (median age 64 yr, interquartile range
[IQR] 58-72) with suspected early cancer in Barrett's esophagus who were referred
to our hospital for endoscopic therapy were prospectively included in a
standardized staging program with upper gastrointestinal endoscopy, EUS (7.5 MHz
in all cases plus 12.5 or 20 MHz for elevated and/or depressed lesions), CT of
the chest and upper abdomen, and abdominal ultrasonography. The results were
summarized in accordance with the TNM classification. On the basis of the lymph
node findings on CT and/or EUS, the patients were assigned to three categories:
C1, no suspicious lymph nodes; C2, paraesophageal lymph nodes < or =1 cm in size
at the tumor level, lymph nodes > or =1 cm in size not at the tumor level in the
mediastinum or celiac trunk; and C3, paraesophageal lymph nodes > 1 cm in size at
the tumor level. The EUS and CT findings were checked every 6 months in patients
who underwent endoscopic treatment. Surgical resection was scheduled in operable
patients if staging showed a T category higher than T1 and/or the lymph node
staging was assessed as C3. Patients with suspected submucosal infiltration
underwent diagnostic endoscopic resection, and if submucosal involvement was
confirmed were referred for surgery. RESULTS: The median follow-up period was 25
months (IQR 19.5-30.0). The T category diagnosed with CT was < or = T1 in all
patients. On EUS, the T category was classified as T1 in 92% of cases (N = 92)
and as > T1 in 8% (N = 8, p < 0.05). Enlarged lymph nodes (C2 and C3) were
detected in 45% of the patients. Significantly more C2 lymph nodes were diagnosed
with EUS than CT (28 vs 19, p < 0.05). Lymph nodes at the level with the highest
suspicion, C3, were detected using CT in only three of nine cases. Sensitivity of
CT for N staging was not acceptable compared with EUS (38%vs 75%). No extranodal
metastases were found on CT. CONCLUSIONS: In suspected early cancer in Barrett's
esophagus, EUS is superior to CT for T staging and N staging. As CT had no
influence on the TNM classification in any of these patients, it may be possible
to dispense with this method as a staging procedure in patients with cancer in
Barrett's esophagus. By contrast, EUS is required in order to differentiate
between patients with cancer in Barrett's esophagus in whom endoscopic therapy is
suitable and those in whom surgical treatment is required.
PMID- 17032187
TI - Diagnosis and outcome of small bowel tumors found by capsule endoscopy: a three
center Australian experience.
AB - OBJECTIVE: The objective of the study was to examine diagnosis and outcome in a
series of patients with small bowel tumors detected by capsule endoscopy (CE) in
three Australian centers. METHODS: Review of prospectively collected data from
416 CEs identified 27 tumors in 26 patients. Clinical parameters, tumor
histology, and follow-up are reported. RESULTS: Twenty-seven tumors were
identified in 26 patients (mean age 61 +/- 13.7 yr). Indications for CE were
obscure gastrointestinal (GI) bleeding (21), suspected tumor (3), abdominal pain
(1), diarrhea (1). Prior radiology found a possible lesion in 8 of 23 (35%). Nine
tumors were proven benign: hamartoma (4), cystic lymphangioma (1), primary
amyloid (1), lipoma (1). Two lesions were non-neoplastic: heterotopic gastric
mucosa and inflammatory fibroid polyp. Seventeen tumors were malignant: five
adenocarcinomas, six carcinoids, two melanoma metastases, two gastrointestinal
stromal tumors (GIST), one colon carcinoma metastasis, one non-Hodgkin's
lymphoma. Tumors were surgically resected in 23 patients. Resection was
considered curative in 12 (52%). Mean duration of follow-up was 26 +/- 13.7
months. Of the five patients with primary adenocarcinoma only one remains disease
free. Three of the six with carcinoid tumors have had no recurrence up to 51
months postresection. Both patients with GIST are disease free. Anemia resolved
after surgery in the patients with melanoma. CONCLUSIONS: Small bowel tumors are
a significant finding at CE and are often missed by other methods of
investigation. In many patients, detection of a tumor alters management and
improves outcome. Even in malignant lesions, treatment is potentially curative in
the absence of metastatic disease.
PMID- 17032188
TI - Higher prevalence and severity of hepatic encephalopathy in patients with HCV
cirrhosis and diabetes mellitus: is presence of autonomic neuropathy the missing
part of the puzzle?
AB - Hepatic encephalopathy (HE) is a complex and variable neuropsychiatric syndrome
that is seen in patients with acute and chronic liver diseases. The presence or
severity of HE does not always show a strong and consistent relationship with the
severity of liver disease or portal hypertension suggesting that other
predisposing or precipitating factors may be involved. In this issue of the
journal, it has been suggested that DM may contribute to the presence and
severity of HE independent of the severity of liver disease in patients with HCV
cirrhosis. This editorial examines the limitations of the study and potential
mechanisms that could explain the relationship between DM with HE including the
role of autonomic neuropathy.
PMID- 17032189
TI - Metabolic syndrome is associated with greater histologic severity, higher
carbohydrate, and lower fat diet in patients with NAFLD.
AB - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic
manifestation of metabolic syndrome. Insulin resistance (IR) is a key component
of metabolic syndrome. The aim was to determine the dietary composition, physical
activity, and histologic severity between NAFLD patients with and without
metabolic syndrome. METHODS: Ninety-one patients with NAFLD completed the Block
Food Frequency Questionnaire and the Paffenbarger Physical Activity
Questionnaire. IR was assessed by the homeostasis model assessment (HOMA) index.
Metabolic syndrome was defined by the ATP III clinical definition. Nonalcoholic
steatohepatitis (NASH) Clinical Network Scoring System was used to determine the
histologic severity of NAFLD. RESULTS: Thirty-one patients (34%) had metabolic
syndrome. Patients with metabolic syndrome had a higher HOMA index (7.66 vs 4.45,
p = 0.04), and consumed more carbohydrates (51%vs 45%, p = 0.03) and less fat
(34%vs 40%, p = 0.01) compared with those without metabolic syndrome; total daily
calorie, protein consumption, and physical activity were similar between the two
groups. Patients with metabolic syndrome had higher scores for steatosis (2.0 +/-
0.8 vs 1.37 +/- 1, p = 0.02), NASH activity (4.13 +/- 1.4 vs 3.13 +/- 1.7, p =
0.004), and global NASH score (5.9 +/- 1.7 vs 4.4 +/- 2.3, p = 0.0006) compared
with those without metabolic syndrome. When controlled for other factors
including dietary composition and physical activity, the presence of metabolic
syndrome was a significant risk factor for global NASH severity in addition to
HOMA index and female gender. CONCLUSION: Metabolic syndrome in patients with
NAFLD is associated with a diet containing more carbohydrate and less fat and
greater histologic severity. The role of a carbohydrate-restricted diet in
decreasing the risk for metabolic syndrome and histologic severity should be
assessed in patients with NAFLD.
PMID- 17032190
TI - Integrated psychiatric/medical care in a chronic hepatitis C clinic: effect on
antiviral treatment evaluation and outcomes.
AB - OBJECTIVES: Psychiatric and substance use disorders are common in hepatitis C
patients and represent barriers to antiviral treatment. We evaluated the effect
of integrating psychiatric and medical care on evaluation for and initiation of
antiviral treatment in a cohort of 184 patients with chronic hepatitis C.
METHODS: Integrated care consisted of screening for psychiatric problems with
Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), Beck Depression
Inventory (BDI), Urine Drug Screen (UDS), and Primary Care Posttraumatic Stress
Disorder (PC-PTSD) screens, referral based on specified cutoff scores to an
established mental health (MH) provider, to a colocated psychiatric clinical
nurse specialist (PCNS), or both. Data were collected retrospectively by chart
review. RESULTS: Most patients (149/184, 81.0%) had at least one positive screen,
25.5% had a positive UDS. Among patients with positive screens, 38.3% had
established MH providers, 47.0% had no MH provider and were referred to the PCNS,
and 15.0% refused any psychiatric referral. Patients receiving integrated care
with a colocated PCNS were significantly more likely to complete evaluation for
and start antiviral treatment than other patients with positive screens, and at a
rate similar to that of patients with negative screens. Patients with positive
screens followed by any MH provider had significantly greater adherence to
antiviral therapy than patients without positive screens. CONCLUSION: An
integrated MH and medical approach was associated with rates of antiviral therapy
recommendation and initiation similar to patients without risks for psychiatric
or substance use problems. MH care was associated with improved adherence to
antiviral therapy. Integrated care offers promise as an approach for addressing
psychiatric comorbidity in this traditionally difficult to treat population.
PMID- 17032191
TI - Risk factors for gallstone-related hospitalization during pregnancy and the
postpartum.
AB - OBJECTIVES: Gallbladder disease is a leading nonobstetrical cause for
hospitalization in the first year postpartum. The aim of this study was to define
the incidence and risk factors for postpartum hospitalization as a result of
gallstone-related disease. METHODS: We identified 6,670 women with discharge
diagnoses related to biliary disease from linked birth certificate and hospital
discharge databases for Washington State from 1987 through 2001. Cases were women
with gallstone-related diagnoses at delivery or as primary diagnosis in the
postpartum. Four controls who were within 1 yr postpartum were randomly selected
for each case and matched for year of delivery. From the birth certificates, we
obtained data about patient demographics, reproductive history, and pregnancy
related risk factors. In a retrospective case-control study, we developed
multiple logistic regression models to identify independent risk factors for
hospitalization. RESULTS: We identified 6,211 women as cases (0.5% of all births)
during the study period. The median time to hospitalization was 95 days
(interquartile range 46-191 days), with a median length of stay of 3 days.
Seventy-six percent were diagnosed with uncomplicated cholelithiasis, 16% with
pancreatitis, 9% with acute cholecystitis, and 8% with cholangitis. Seventy-three
percent of hospitalized women underwent cholecystectomy, and 5% underwent
endoscopic retrograde cholangiopancreatography (ERCP). On multivariate analysis,
independent risk factors for hospitalization included maternal race, age, being
overweight or obese prepregnancy, pregnancy weight gain, and estimated
gestational age. CONCLUSIONS: Hospitalization for gallstone-related disease is
common in the first year postpartum, most commonly for uncomplicated
cholelithiasis. Risk factors for hospitalization include prepregnancy body mass
index, race, Hispanic ethnicity, and maternal age.
PMID- 17032192
TI - Antiviral therapy decreases hepatic venous pressure gradient in patients with
chronic hepatitis C and advanced fibrosis.
AB - BACKGROUND: Antiviral therapy (AVT) may improve liver histology in patients with
advanced viral hepatitis but its effect on portal pressure remains unknown. AIM:
This study was aimed to evaluate the influence of antiviral therapy (AVT) on
hepatic venous pressure gradient (HVPG) in hepatitis C virus infected patients
with portal hypertension. METHODS: Twenty compensated patients with chronic
hepatitis C, fibrosis stage 3 or 4 and HVPG > 5 mmHg received PEG-IFN alpha2b
plus ribavirin. Every patient underwent liver biopsy and portal pressure
measurements before and immediately after AT. Biopsies were evaluated according
to METAVIR score. RESULTS: HVPG significantly dropped in all but one treated
patient, with a mean (SD) reduction of 28.2 (12)%[13.8 (5.6) Vs. 10.2 (3.8) mmHg,
p = 0.005]. The percentage of HVPG decrease was significantly greater in patients
who achieved a virological end of treatment response [26.2 (12.5)% Vs. 12.7
(8.5)%, p = 0.05] and in those with a decrease of at least 2 points in the grade
of inflammation [35.7 (4.5)% Vs. 22.1 (9.5)%, p = 0.015]. Nine out of 11 patients
with baseline HVPG > or = 12 mmHg showed a decrease greater than 20% (3/11) or
under the 12 mmHg threshold (6/11). CONCLUSIONS: AVT reduces HVPG in compensated
patients with advanced hepatitis C (fibrosis stage 3 or 4) and portal
hypertension.
PMID- 17032194
TI - Outcome of surgical versus percutaneous drainage of abdominal and pelvic
abscesses in Crohn's disease.
AB - OBJECTIVE: Abdominal and pelvic abscesses are a common complication of Crohn's
disease. We studied the effect of the initial choice of therapy on time to
resolution of abdominal and pelvic abscesses. METHODS: We recorded clinical,
laboratory, and radiographic data on all adult patients with Crohn's disease and
abdominal or pelvic abscesses treated at our institution from 1991 to 2001 and
followed > or = 1 yr. Univariate analysis identified variables associated with
initial choice of drainage modality. These variables were included in a Cox
regression model to identify factors independently associated with time to
resolution. RESULTS: Of 66 episodes identified, surgery was the initial modality
in 29 and percutaneous drainage in 37. Median time to resolution was not
different between surgical drainage (25.0 days, range 0-240) and percutaneous
drainage (21.5 days, range 0-182) (p = 0.084). Older age, longer duration of
symptoms prior to drainage, no fistula identified radiographically, immune
modulator use, no rebound tenderness, and admission to the medical service were
factors associated with percutaneous drainage as initial modality. These factors,
when incorporated in a Cox regression model, did not significantly affect the
time to resolution. Days from onset of symptoms to radiographic diagnosis or
drainage were independently associated with time to resolution of the abscess.
CONCLUSION: Time to resolution of abdominal or pelvic abscesses in Crohn's
disease is similar with percutaneous drainage and surgery. One-third of patients
treated with percutaneous drainage required surgery within 1 yr. Earlier
intervention for abdominal and pelvic abscesses is associated with shorter time
to resolution.
PMID- 17032193
TI - Erythropoietin treatment is associated with more severe thrombocytopenia in
patients with chronic hepatitis C undergoing antiviral therapy.
AB - BACKGROUND: Erythropoietin (EPO) not only stimulates erythropoiesis but also
thrombopoiesis. As pegylated-interferon-alpha(PEG-IFN-alpha)-induced
thrombocytopenia may become a limiting factor for continuation of therapy, the
present study investigated if EPO can alleviate PEG-IFN-alpha induced
thrombocytopenia. Further, we hypothesize that EPO increases platelet reactivity
and protease activated receptor 1 (PAR-1) expression during combination antiviral
therapy. METHODS: Forty patients with chronic hepatitis C received either 10,000
IU EPO 3 x/week or placebo in a randomized, placebo-controlled, double-blinded
fashion for 4 wk and combination antiviral therapy with PEG-IFN-2a and ribavirin.
RESULTS: EPO alleviated the decrease in hemoglobin during combination antiviral
therapy with ribavirin (10%vs 20%, p < 0.0001). Platelet counts decreased
stronger in EPO than in placebo group on day 28 (p= 0.007). EPO induced a 40%
increase in PAR-1 (p < 0.0001), which was accompanied by 100% increase in
platelet reactivity (p < 0.0001). PFA-100 platelet plug formation time and PEG
IFN-alpha-induced vWF-increase were not different between study groups.
CONCLUSIONS: Treatment with EPO alleviated the decrease in hemoglobin but
worsened PEG-IFN-alpha induced thrombocytopenia after the first 4 wk of
combination therapy. EPO caused PAR-1 receptor upregulation on platelets, which
promoted an increase in platelet reactivity without affecting PFA-100 platelet
plug formation time. EPO is not a useful option for short-term support of
platelet production during antiviral therapy.
PMID- 17032195
TI - Bowel dysfunction in patients with motor complete spinal cord injury: clinical,
neurological, and pathophysiological associations.
AB - BACKGROUND: Abnormal bowel function is a key problem in patients with spinal cord
injury (SCI). Previous works provided only partial information on colonic transit
time (CTT) or anal dysfunction but did not identified a comprehensive neurogenic
bowel pattern. AIM: To evaluate clinical, neurological, and pathophysiological
counterparts of neurogenic bowel in patients with motor complete SCI. METHODS:
Fifty-four patients (56% men, mean age 35 yr) with chronic motor complete SCI
(mean evolution time 6 yr) were evaluated: 41% with injuries above T7 (> T7) and
59% with injuries below T7 (< T7); patients were also classified according to the
presence or not of sacral spinal reflexes. Clinical assessment, total and
segmental CTT quantification, anorectal function evaluation by manometry,
intrarectal balloon distension, and surface electromyography were performed.
RESULTS: Three different neuropathophysiological patterns were observed: Pattern
A, present in > T7 injuries, characterized by very frequent constipation (86%)
with significant defecatory difficulty and not very severe incontinence (Mean
Wexner score 4.5); it was related to moderate delay in CTT (mainly in the left
colon and recto-sigma), incapacity to increase the intra-abdominal pressure, and
the absence of anal relaxation during the defecatory maneuvre; Pattern B, present
in < T7 injuries with preserved sacral reflexes, characterized by not so frequent
constipation (50%) but very significant defecatory difficulty and not very severe
incontinence (Wexner 4.8); the pathophysiological counterpart was a moderate
delay in CTT, capacity to increase intra-abdominal pressure, increased anal
resistance during the defecatory maneuver, and presence of external anal
sphincter (EAS) contraction when intra-abdominal pressure increased and during
rectal distension; Pattern C, present in < T7 injuries without sacral reflexes,
characterized by not very frequent constipation (56%) with less defecatory
difficulty and greater severity of incontinence (Wexner 7.2); this was associated
with severe delay in CTT (mainly in the left colon), capacity to increase intra
abdominal pressure, absence of anal resistance during the defecatory maneuver,
and absence of EAS contraction when intra-abdominal pressure increased and during
rectal distension. CONCLUSION: In patients with motor complete SCI, we were able
to define three different neuropathophysiological patterns that are associated
with bowel function abnormalities and clinical complaints; this might be of help
when designing therapeutic strategies.
PMID- 17032196
TI - Patterns of care for adjuvant therapy in a random population-based sample of
patients diagnosed with colorectal cancer.
AB - OBJECTIVES: Over the past decade, clinical trials have proved the efficacy of
treatments for colorectal cancer (CRC). This study tracks dissemination of these
treatments for patients diagnosed with stage II and III disease and compares risk
of death for those who received guideline therapy to those who did not. METHODS:
We conducted a stratified randomly sampled, population-based study of CRC
treatment trends in the United States. Multivariate models were used to explore
patient characteristics associated with receipt of treatments. We pooled data
with a previous study-patients diagnosed in 1987-1991 and 1995. Cox proportional
hazards models were used to assess observed cause-specific and all-cause
mortality. RESULTS: In 2000, guideline therapy receipt decreased among stage III
rectal cancer patients, but increased for stage III colon and stage II rectal
cancer patients. As age increased, likelihood of receiving guideline treatment
decreased (p < 0.0001). Overall, race/ethnicity was significantly associated with
guideline therapy (p = 0.04). Rectal patients were less likely to have received
guideline treatment. Consistent with randomized clinical trial findings, all
cause mortality was lower in patients who received guideline therapy, regardless
of Charlson comorbidity score. CONCLUSIONS: Mortality was decreased in patients
receiving guideline therapy. Although, rates of guideline-concordant therapy are
low in community clinical practice, they are apparently increasing. Newer
treatment (oxaliplatin, capecitabine) started to disseminate in 2000. Racial
disparities, present in 1995, were not detected in 2000. Age disparities remain
despite no evidence of greater chemotherapy-induced toxicity in the elderly. More
equitable receipt of cancer treatment to all segments of the community will help
to reduce mortality.
PMID- 17032197
TI - MUC4-expressing pancreatic adenocarcinomas show elevated levels of both T1 and T2
cytokines: potential pathobiologic implications.
AB - OBJECTIVE: The human MUC4 mucin plays an important role in the pathogenesis of
pancreatic cancer. Recently, we have demonstrated that MUC4 expression in
pancreatic tumor cells is regulated by interferon-gamma (IFNgamma) and by
retinoic acid via transforming growth factor beta 2 (TGFbeta-2). In the present
study, we established the pathobiological association of various cytokines and
MUC4 in pancreatic tumor tissues and tumor cell lines. METHODS: Using
semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and/or
immunohistochemical analyses, we examined the expression of MUC4, IFNgamma,
TGFbetas, and several immunologically relevant cytokines in a panel of 11
pancreatic adenocarcinomas (PA), three normal pancreatic (NP) tissue specimens,
and 11 pancreatic tumor cell lines. RESULTS: Our data revealed that both MUC4 and
IFNgamma were expressed at moderate to high levels in the majority of PA, while
being undetectable in NP. Moreover, transcript for interleukin 2 (IL-2), a known
marker of activated T helper 1 (TH1) lymphocytes, exhibited an expression profile
similar to IFNgamma, suggesting a role of these immune effector cells as a
potential source of IFNgamma in PA. Of note, IFNgamma protein was detected in the
inflamed tissues neighboring tumor areas. Furthermore, TGFbetas were expressed by
most cell lines and frequently upregulated in PA compared with NP. Interestingly,
both IL-12 and IL-10, two key cytokines of the TH1 and TH2 pathways,
respectively, were expressed at higher levels in PA relative to NP. CONCLUSIONS:
These observations support the potential implication of IFNgamma and TGFbetas in
MUC4 regulation in vivo and suggest a complex interaction of TH1 and TH2
signaling in the pancreatic tumor microenvironment. These findings may provide
useful insights into the pathobiology of pancreatic cancer.
PMID- 17032198
TI - Role of MUC genes and mucins in pancreatic neoplasia.
PMID- 17032199
TI - Rotavirus infection frequency and risk of celiac disease autoimmunity in early
childhood: a longitudinal study.
AB - OBJECTIVE: Few studies have assessed the role of specific gastrointestinal
infections in celiac disease. We investigated whether increased frequency of
rotavirus infection, a common cause of gastrointestinal infection and
inflammation, predicts increased risk of celiac disease autoimmunity. METHODS: A
cohort of 1,931 children from the Denver metropolitan area who carried celiac
disease human leukocyte antigen (HLA) risk alleles were followed from infancy for
development of celiac disease autoimmunity, defined as positivity at two or more
subsequent clinic visits for tissue transglutaminase (tTG) autoantibodies
measured using a radioimmunoassay with human recombinant tTG. Blood samples were
obtained at ages 9, 15, and 24 months, and annually thereafter. Rotavirus
antibodies were assayed using an indirect enzyme immunoassay in serial serum
samples from each case and two matched controls. Frequency of infections were
estimated by the number of increases (> 2 assay coefficient of variation) in
rotavirus antibody between clinic visits. RESULTS: Fifty-four cases developed
celiac disease autoimmunity at a median age of 4.4 yr. Thirty-six had an
intestinal biopsy, of which 27 (75%) were positive for celiac disease. Frequent
rotavirus infections predicted a higher risk of celiac disease autoimmunity
(compared with zero infections, rate ratio 1.94, 95% confidence interval [CI]
0.39-9.56, for one infection and rate ratio 3.76, 95% CI 0.76-18.7, for > or = 2
infections, rate ratio for trend per increase in number of infections = 1.94, 95%
CI 1.04-3.61, p = 0.037). The result was similar after adjustment for gender,
ethnic group, maternal education, breast-feeding, day-care attendance, number of
siblings, season of birth, and number of HLA DR3-DQ2 haplotypes. CONCLUSIONS:
This prospective study provides the first indication that a high frequency of
rotavirus infections may increase the risk of celiac disease autoimmunity in
childhood in genetically predisposed individuals.
PMID- 17032200
TI - Clinicopathological features of focal nodular hyperplasia-like nodules in 130
cirrhotic explant livers.
AB - OBJECTIVES: Focal nodular hyperplasia-like nodules (FNH-like nodules) are focal
lesions occurring in liver cirrhosis and are morphologically very similar to
classical FNH in an otherwise normal liver. They are sometimes misdiagnosed as
hepatocellular carcinoma (HCC) on imaging because both types of lesions show
arterial-phase enhancement. Although the morphological, immunohistochemical, and
imaging features of FNH-like nodules are well-known, their pathogenesis and role
in hepatocarcinogenesis have not been studied in detail. Therefore, we performed
a detailed pathological evaluation of 130 cirrhotic explant livers and correlated
these data with the clinical features of the patients. METHODS: All cirrhotic
explant livers were uniformly sliced at 5-mm intervals and all detected focal
lesions were microscopically classified according to internationally accepted
criteria. The obtained data regarding FNH-like nodules were then correlated with
other pathological findings and with clinical data obtained during pretransplant
evaluation and recorded in a database. RESULTS: FNH-like nodules were present in
15% of patients and their small size (75% of cases < 1 cm) appears to preclude
detection by imaging in almost all cases. The presence of esophageal varices and
pretransplant treatment with chemoembolization were independently and
significantly associated with the presence of FNH-like nodules. There were no
associations between FNH-like nodules on the one hand and low-grade dysplastic
nodules, high-grade dysplastic nodules, and HCCs on the other hand. CONCLUSIONS:
The clinicopathological features of FNH-like nodules support the hypothesis that
vascular alterations in liver cirrhosis play an important role in their
pathogenesis and that FNH-like nodules do not have an increased risk of malignant
transformation.
PMID- 17032201
TI - Efficacy of enteral nutrition for the treatment of pancreatitis using standard
enteral formula.
AB - BACKGROUND AND AIMS: Elemental formula delivered distal to the ligament of Treitz
has demonstrated efficacy in patients with pancreatitis, presumably by decreasing
pancreatic stimulation. Few data exist on the use of standard enteral formula in
such patients. This study describes the outcomes of pancreatitis patients managed
with long-term standard enteral nutrition (EN). METHODS: One hundred twenty-six
patients managed at the University of Virginia Health System with pancreatitis
requiring nutritional support between August 2000 and June 2004 received a
standard formula delivered distal to the ligament of Treitz and were followed
prospectively to resolution of their disease process. Predictors of improvement
in CT Severity Index, duration of EN, and length of hospital stay were
identified. Changes in body weight and serum albumin were determined. RESULTS:
Mean age was 50.8 +/- 15.2 yr (male, 83). Etiology included alcohol (46),
gallstones (49), idiopathic (15), post-ERCP (7), drug (5), hyperlipidemia (3),
and pancreas divisum (1). EN lasted a median of 18.9 (2.4 to 111.7) wk. Median CT
Severity Index decreased from 4 to 2 (p < 0.001). Underweight patients gained 9.8
lbs; overweight and obese patients lost 7.2 and 28.8 lbs, respectively. Albumin
concentration increased from 3 to 3.8 g/dL (p < 0.001). CONCLUSIONS: Standard
enteral formula is effective in the management of patients with complicated
pancreatitis.
PMID- 17032202
TI - Overweight in celiac disease: prevalence, clinical characteristics, and effect of
a gluten-free diet.
AB - BACKGROUND: It is well established that a minority of celiac patients present
with "classic" symptoms due to malabsorption. However, few studies have focussed
on the distribution of body mass index (BMI) in celiac populations and its
relationship to clinical characteristics, or on its response to treatment.
METHODS: We reviewed BMI measurements and other clinical and pathological
characteristics from a database of 371 celiac patients diagnosed over a 10-yr
period and seen by a single gastroenterologist. To assess response to gluten
exclusion, we compared BMI at diagnosis and after 2 yr treatment in patients with
serological support for dietary compliance. RESULTS: Mean BMI was 24.6 kg/m2
(range 16.3-43.5). Seventeen patients (5%) were underweight (BMI < 18.5), 211
(57%) were normal, and 143 (39%) were overweight (BMI > or = 25), including 48
(13% of all patients) in the obese range (BMI > or = 30.0). There was a
significant association between low BMI and female gender, history of diarrhea,
reduced hemoglobin concentration, reduced bone mineral density (BMD),
osteoporosis, and higher grades (subtotal/total) of villous atrophy. Of patients
compliant with a gluten-free diet, 81% had gained weight after 2 yr, including
82% of initially overweight patients. CONCLUSIONS: Few celiac patients are
underweight at diagnosis and a large minority is overweight; these are less
likely to present with classical features of diarrhea and reduced hemoglobin.
Failed or delayed diagnosis of celiac disease may reflect lack of awareness of
this large subgroup. The increase in weight of already overweight patients after
dietary gluten exclusion is a potential cause of morbidity, and the gluten-free
diet as conventionally prescribed needs to be modified accordingly.
PMID- 17032203
TI - Management and treatment of hepatitis C viral infection: recommendations from the
Department of Veterans Affairs Hepatitis C Resource Center program and the
National Hepatitis C Program office.
AB - Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the
general U.S. population and 5-10% of veterans who use Department of Veterans
Affairs medical services. Chronic HCV is clearly linked to the development of
cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring
liver transplantation. The consequences of HCV infection constitute a significant
disease burden and demonstrate the need for effective medical care. Treatment of
chronic HCV is aimed at slowing disease progression, preventing complications of
cirrhosis, reducing the risk of HCC, and treating extrahepatic complications of
the virus. As part of a comprehensive approach to HCV management, antiviral
therapy with peginterferon alfa combined with ribavirin is the current standard
of care. Antiviral therapy should be provided to those individuals who meet
criteria for treatment and who are at greatest risk for progressive liver
disease. Many of these patients may have comorbid medical and psychiatric
conditions, which may worsen while on antiviral therapy. Current antiviral
regimens are associated with significant adverse effects that can lead to
noncompliance, dose reduction, and treatment discontinuation. To overcome these
barriers and to address these issues, it has become crucial to facilitate a
multidisciplinary team who can respond to and provide HCV-specific care and
treatment. Screening for HCV, preventing transmission, delaying disease
progression, ensuring appropriate antiviral therapy, and managing treatment
related adverse effects can improve patient quality of life, treatment adherence,
and ultimately, improve patient outcomes.
PMID- 17032204
TI - Practice guidelines in acute pancreatitis.
PMID- 17032205
TI - Epidemiology of childhood constipation: a systematic review.
AB - OBJECTIVE: A systematic review of the published literature was performed to
assess the prevalence, incidence, natural history, and comorbid conditions of
functional constipation in children. METHODS: Articles were identified through
electronic searches in Medline, Embase, Cochrane Central Library, Cinhal and
PsychInfo databases. Study selection criteria included: (1) epidemiology studies
of general population, (2) on the prevalence of constipation without obvious
organic etiology, (3) in children from 0 to 18 yr old, and (4) published in
English and full manuscript form. RESULTS: Eighteen studies met our inclusion
criteria. The prevalence of childhood constipation in the general population
ranged from 0.7% to 29.6% (median 8.9; inter quartile range 5.3-17.4). The
prevalence of constipation defined as defecation frequency of < 3/wk varied from
0.7% to 29.6% (median 10.4; inter quartile range 1.3-21.3). Identified studies
originated from North America (N = 4), South America (N = 2), Europe (N = 9), the
Middle-East (N = 1), and Asia (N = 2). Variance of gender specific prevalence was
reported in seven studies and five of seven studies reported no significant
difference between boys and girls. The age group in which constipation is most
common could not be assessed with certainty. Socioeconomic factors were not found
to be associated with constipation. CONCLUSION: Childhood constipation is a
common problem worldwide. Most studies report similar prevalence rates for boys
and girls. Large epidemiologic studies with the use of generally accepted
diagnostic criteria are needed to define the precise prevalence of constipation.
PMID- 17032207
TI - "Does fecal occult blood testing really reduce mortality? A reanalysis of
systematic review data." by Moayyedi P and Achkar E.
PMID- 17032208
TI - Mistaking "life" (as we know it) for "disease".
PMID- 17032210
TI - The low incidence of bacterial infections could be a protective factor against
variceal bleeding per se in hemodynamic responders to propranolol.
PMID- 17032211
TI - Regression of hepatocellular carcinoma due to cyclooxygenase (COX)-2 inhibitor.
PMID- 17032212
TI - Magnetic resonance imaging meets immunology: an unusual combination of diagnostic
tools leads to the diagnosis actinomycosis.
PMID- 17032213
TI - Small cell carcinoma of the large bowel: a rare, but very aggressive malignancy.
PMID- 17032214
TI - Pneumatic dilatations for achalasia: a safe and effective choice for most
patients.
PMID- 17032218
TI - Inhibition of aflatoxin B production of Aspergillus flavus, isolated from soybean
seeds by certain natural plant products.
AB - AIMS: The inhibitory effect of cowdung fumes, Captan, leaf powder of Withania
somnifera, Hyptis suaveolens, Eucalyptus citriodora, peel powder of Citrus
sinensis, Citrus medica and Punica granatum, neem cake and pongamia cake and
spore suspension of Trichoderma harzianum and Aspergillus niger on aflatoxin B(1)
production by toxigenic strain of Aspergillus flavus isolated from soybean seeds
was investigated. METHODS AND RESULTS: Soybean seed was treated with different
natural products and fungicide captan and was inoculated with toxigenic strain of
A. flavus and incubated for different periods. The results showed that all the
treatments were effective in controlling aflatoxin B(1) production. Captan, neem
cake, spore suspension of T. harzianum, A. niger and combination of both reduced
the level of aflatoxin B(1) to a great extent. Leaf powder of W. somnifera, H.
suaveolens, peel powder of C. sinensis, C. medica and pongamia cake also
controlled the aflatoxin B(1) production. CONCLUSIONS: All the natural product
treatments applied were significantly effective in inhibiting aflatoxin B(1)
production on soybean seeds by A. flavus. SIGNIFICANCE AND IMPACT OF THE STUDY:
These natural plant products may successfully replace chemical fungicides and
provide an alternative method to protect soybean and other agricultural
commodities from aflatoxin B(1) production by A. flavus.
PMID- 17032219
TI - Evaluation and applicability of a purification method coupled with nested PCR for
the detection of Toxoplasma oocysts in water.
AB - AIMS: To describe the development, evaluation and applicability of a complete
method for the detection of Toxoplasma gondii in water. METHODS AND RESULTS: The
method incorporated concentration of water samples by Al(2)(SO(4))(3)
flocculation, purification by discontinuous sucrose gradients and detection of
toxoplasmic DNA by 18S-rRNA nested PCR. Tap water replicates and natural water
samples were seeded with defined numbers of Toxoplasma oocysts and processed for
evaluation studies. When applied to environmental samples, the method gave
highest detection sensitivities of 100 oocysts in river water and 10 oocysts in
well- and sea water. The method was finally applied in 60 water samples of
different quality and origin collected over a 14-month period. Toxoplasmic DNA
was detected in four samples. CONCLUSIONS: The method offers an alternative
towards improving current methods that can be used for the detection of
Toxoplasma oocysts in environmental water samples. SIGNIFICANCE AND IMPACT OF THE
STUDY: The method in its current form will be helpful for assessment of
Toxoplasma contamination in water resources, particularly after outbreak events.
PMID- 17032220
TI - A preliminary assessment of Bacillus anthracis spore inactivation using an
electrochemically activated solution (ECASOL).
AB - AIM: To evaluate the efficacy of electrochemically activated solution (ECASOL) in
decontaminating Bacillus anthracis Ames and Vollum 1B spores, with and without
changing the source water hardness and final ECASOL pH. METHODS AND RESULTS: Five
different ECASOL formulations were generated, in which the source water hardness
and final ECASOL pH were varied, resulting in cases where significant changes in
free available chlorine (FAC) and oxidative-reduction potential (ORP) were
observed. B. anthracis Ames and Vollum 1B spores were suspended in the various
ECASOL formulations for 30 min, and decontamination efficacy was determined;
calcium hypochlorite [5% high-test hypochlorite (HTH)] was used as a positive
control. The five different ECASOL formulations yielded mean FAC levels ranging
from 305 to 464 ppm, and mean ORP levels ranging from +826 to +1000 mV. Exposure
to all the ECASOL formulations and 5% HTH resulted in >or=7.0 log reductions in
both B. anthracis Ames and Vollum 1B spores. CONCLUSIONS: The present testing
demonstrated that ECASOL with a minimum of c. 300-ppm FAC levels and +800-mV ORP
inactivated the B. anthracis spores in suspension, similar to 5% HTH.
SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide information for
decontaminating B. anthracis Ames and Vollum 1B spores in suspension using
ECASOL.
PMID- 17032221
TI - Subinhibitory concentrations of cinnamaldehyde interfere with quorum sensing.
AB - AIMS: To investigate the effect of cinnamaldehyde (CA) on transcription from
selected quorum sensing (QS) promoters. METHODS AND RESULTS: The action of CA on
QS was assayed using three E. coli green fluorescent protein (GFP) based
bioreporters (two inducible and the other constitutive) and two Vibrio harveyi
bioluminescent reporter strains. LuxR-mediated transcription from the P(luxI)
promoter, which is induced by 3-oxo-C6-homoserine lactone (HSL), was reduced by
70 per cent following exposure to 200 micromol l(-1) CA (26 ppm). The
bioluminescence of Vibrio harveyi BB886, which is mediated by 3-hydroxy-C4-HSL,
was reduced by 55 per cent after exposure to 60 micromol l(-1) CA (8 ppm), and
100 micromol l(-1) CA (13 ppm) inhibited the bioluminescence of the autoinducer-2
(AI-2) responsive reporter strain V. harveyi BB170 by nearly 60 per cent. CA did
not inhibit the growth of the bioreporter strains at these concentrations. CA had
a minimal effect on LasR promoter activity, induced by 3-oxo-C12-HSL.
CONCLUSIONS: Low concentrations of CA were effective at inhibiting two types of
acyl homoserine lactone mediated QS, and also autoinducer-2 mediated QS.
SIGNIFICANCE AND IMPACT OF STUDY: Because CA is widely used in the food and
flavour industries, its potential to affect bacterial QS regulated processes
should be recognized.
PMID- 17032222
TI - Molecular identification of Bacillus thuringiensis var. israelensis to trace its
fate after application as a biological insecticide in wetland ecosystems.
AB - AIMS: To determine the fate of viable Bacillus thuringiensis var. israelensis
(Bti) spores dispersed in the environment, using a universally applicable
molecular detection methodology. METHODS AND RESULTS: Soil samples were spread on
growth medium, after a temperature selection of the spores. A PCR amplification
of the cry4Aa and cry4Ba insecticidal genes was applied on the colonies.
Ribotyping was performed subsequently. This combined molecular method proved to
be very specific for Bti, which was easily differentiated from the other B.
thuringiensis serovars. A site regularly treated with Vectobac-G was chosen
within the 'Bolle di Magadino' natural reserve, and monitored throughout 1 year
for the detection of Bti spores. The results showed that the numbers were
relatively high after insecticidal applications (1.4 x 10(5) CFU g(-1)), and
decreased approx. 10-fold after 220 days. A successive treatment induced a new
increase. CONCLUSIONS: The results show that yearly repeated use of Vectobac-G
does not seem to have a major ecological impact on the 'Bolle di Magadino'
natural reserve. Bti spores followed a trend leading to their eventual
disappearance from the ecosystem, despite the seasonal application of this
biological insecticide for more than a decade. SIGNIFICANCE AND IMPACT OF THE
STUDY: The molecular identification of Bti cells through the PCR analysis of the
delta-endotoxins genes coupled to ribotyping, is an innovative method, that has
enabled the identification of this organism into wetland environments.
PMID- 17032223
TI - Inhibitory effects of Lactobacillus acidophilus lysates on the cytotoxic activity
of shiga-like toxin 2 produced from Escherichia coli O157:H7.
AB - AIMS: The purpose of this study was to characterize the degree to which four cell
lysates obtained from Lactobacillus acidophilus strains affected the cytotoxic
activity of Escherichia coli O157:H7 in vitro and in vivo. METHODS AND RESULTS:
In a cytotoxic inhibition test that used 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide and toxin-binding ELISA assays, the activity of shiga
like toxin 2 (Stx-2) was inhibited profoundly by the cell lysates (10 mg ml(-1))
from two strains of L. acidophilus A4 and 30SC (>85% of survival rates compared
with the control) among the five strains tested. In particular, a significant
decline in the virulence level of E. coli O157:H7, under the presence of the cell
lysates of L. acidophilus A4, was observed by killing assay of Caenorhabditis
elegans in vivo model. CONCLUSIONS: According to our results, L. acidophilus
strains might be capable of attenuating the virulence of Stx-2 produced from E.
coli O157:H7. SIGNIFICANCE AND IMPACT OF THE STUDY: The cell lysates of L.
acidophilus can be applied to a variety of foods, and can be used as adjuncts for
the inhibition of Stx-2-mediated cytotoxicity.
PMID- 17032224
TI - In vitro growth inhibition of Helicobacter pylori by lactobacilli belonging to
the Lactobacillus plantarum group.
AB - AIMS: The aim of this study was to test and locate the in vitro anti-Helicobacter
activity of seven Lactobacillus strains belonging to Lactobacillus plantarum
group. METHODS AND RESULTS: Growth inhibition of H. pylori was tested using a
well-plate assay. Of the strains displaying the strongest growth inhibition, a L.
plantarum isolated from sauerkraut (MLBPL1) was chosen for further studies. The
detected anti-Helicobacter activity of MLBPL1 was mainly associated with cell
wall, and to a minor extent with the culture supernatant. The active component,
which was determined to be between 3 and 10 kDa in size, retained its activity
after 10 min treatment at 100 degrees C. The activity was present when MLBPL1 was
cultivated in rich laboratory cultivation medium MRS and in different food
matrices. CONCLUSIONS: The strains belonging to L. plantarum group showed anti
Helicobacter activity in vitro. The main activity seemed to be associated with
cell wall rather than culture supernatant or intracellular fraction. SIGNIFICANCE
AND IMPACT OF THE STUDY: In view of the rapid spread of resistant H. pylori
strains caused by antibiotic therapy, addition of a fermented food containing L.
plantarum to the conventional antibiotic treatment of Helicobacter infection
could establish a potential complementary means to suppress the infection.
PMID- 17032225
TI - Simple conjugation and outgrowth procedures for tagging vibrios with GFP, and
factors affecting the stable expression of the gfp tag.
AB - AIM: Our goal was to develop a simple system for tagging wild-type marine
bacteria with gfp. METHODS AND RESULTS: Escherichia coli strain CC118lambdapir
carrying the conjugative helper plasmid pEVS104 and the gfp-containing plasmid
pKV111 was used to transfer gfp to Vibrio recipients. Four different media were
tested for their ability to support the growth of recipients, but not the E. coli
donor, to allow powerful enrichment of gfp-tagged wild-type vibrios from mating
mixes. Forty-three vibrio strains, representing 39 different species, were
successfully tagged with gfp using the conjugative transfer from E. coli followed
by selective outgrowth at 15 degrees C on ZoBell 2216E agar containing 0.5%
sodium alginate. Using this outgrowth medium, colonies of GFP-expressing vibrio
clones were detectable within 4 days. The percentage of visibly fluorescent cells
in three representative GFP-tagged vibrios was higher at 15 degrees C than at 20
or 25 degrees C (c. 50% vs. 45% or 40%, respectively), and was also higher during
the aerobic rather than the anaerobic culturing (c. 50% vs. 35%, respectively).
CONCLUSIONS: We found a simple selective outgrowth technique that enabled us to
isolate a wide variety of GFP-tagged marine vibrios following the conjugative
transfer of gfp from E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: Tagging cells
with GFP and related fluorescent proteins is a powerful approach for
investigating the bacteria in situ, particularly during the colonization of
hosts. The simple and cost-effective outgrowth condition described in this study
could be applied to construct a wide variety gfp-tagged marine bacteria.
PMID- 17032226
TI - Effect of suspension media on nonthermal inactivation of Escherichia coli.
AB - AIMS: To investigate the influence of suspension media on the survival of
Escherichia coli M23 exposed to nonthermal, lethal stresses. METHODS AND RESULTS:
Populations of E. coli M23 suspended in minimal medium (MM) or in different
nutrient-rich broths were exposed to water activity 0.90 and/or pH 3.5 and
inactivation was determined by culture-based enumeration. In response to the
osmotic or acid challenges, E. coli M23 displayed enhanced survival in MM rather
than in complex broth. That trend was reversed when populations were exposed to
low water activity in combination with low pH. Comparison of microbial survival
in three complex media indicated that even relatively small differences in
composition influenced inactivation. In most media the combination of lethal
stresses resulted in a synergism, which enhanced bacterial inactivation; however,
an exception (tryptone soya broth) was observed. CONCLUSIONS: The suspension
medium strongly influences the inactivation of E. coli M23 by osmotic and/or acid
stresses. This should be considered when comparing studies of microbial survival
that use different media and when broth-derived data are intended to represent
specific environments (e.g. food matrices). SIGNIFICANCE AND IMPACT OF THE STUDY:
The specific effects of synthetic media need to be appreciated when studying
bacterial inactivation in conditions relevant to food-manufacturing regimes.
PMID- 17032227
TI - Use of repetitive DNA sequences to determine the persistence of enteropathogenic
Escherichia coli in vegetables and in soil grown in fields treated with
contaminated irrigation water.
AB - AIMS: Fresh fruits and vegetables are increasingly recognized as vectors for food
borne illness. On farm contamination through contaminated irrigation water is
considered likely source of the pathogen for several outbreaks. The purpose of
this study is to investigate the possible similarity of strains of Escherichia
coli isolated from the soil and vegetables irrigated by treated wastewater.
METHODS AND RESULTS: Seventy-five strains of enteropathogenic Escherichia coli
isolated from vegetables, soil and irrigation water were tested for sensitivity
to antibiotics and shown to be sensitive. The result of enterobacterial
repetitive intergenic consensus (ERIC)-PCR shows similarities between analysed
strains isolated from the three different samples. Moreover strains of E. coli
isolated from vegetables over different periods of time have the same ERIC-PCR
profile. CONCLUSIONS: The isolated strains of enteropathogenic E. coli can
persist in soil and in vegetables growing in fields treated with contaminated
irrigation water for an extended period of time. SIGNIFICANCE AND IMPACT OF THE
STUDY: Contaminated irrigation water can transport pathogenic bacteria, which
persists in the soil for a long period of time and contaminates the vegetables
growing in the field irrigated by this contaminated water.
PMID- 17032228
TI - Antibiotic resistance genes in multidrug-resistant Enterococcus spp. and
Streptococcus spp. recovered from the indoor air of a large-scale swine-feeding
operation.
AB - AIMS: In this study, multidrug-resistant bacteria previously recovered from the
indoor air of a large-scale swine-feeding operation were tested for the presence
of five macrolide, lincosamide and streptogramin (MLS) resistance genes and five
tetracycline (tet) resistance genes. METHODS AND RESULTS: Enterococcus spp. (n =
16) and Streptococcus spp. (n =16) were analysed using DNA-DNA hybridization,
polymerase chain reaction (PCR) and oligoprobing of PCR products. All isolates
carried multiple MLS resistance genes, while 50% of the Enterococcus spp. and 44%
of the Streptococcus spp. also carried multiple tet resistance genes. All
Enterococcus spp. carried erm(A) and erm(B), 69% carried erm(F), 44% carried
mef(A), 75% carried tet(M), 69% carried tet(L) and 19% carried tet(K). All
Streptococcus spp. carried erm(B), 94% carried erm(F), 75% carried erm(A), 38%
carried mef(A), 50% carried tet(M), 81% carried tet(L) and 13% carried tet(K).
CONCLUSIONS: Multidrug resistance among airborne bacteria recovered from a swine
operation is encoded by multiple MLS and tet resistance genes. These are the
first data regarding resistance gene carriage among airborne bacteria from swine
feeding operations. SIGNIFICANCE AND IMPACT OF THE STUDY: The high prevalence of
multiple resistance genes reported here suggests that airborne Gram-positive
bacteria from swine operations may be important contributors to environmental
reservoirs of resistance genes.
PMID- 17032229
TI - Evaluation of antimicrobial activity in Paenibacillus spp. strains isolated from
natural environment.
AB - AIMS: Paenibacillus isolates were selected to test antimicrobial activity against
bacteria, filamentous fungi and yeasts isolates, with the purpose of finding new
bacterium species for microbiological control. METHODS AND RESULTS: Fifty-five
strains belonging to 15 species of Paenibacillus were inoculated on trypticase
soya agar, potato dextrose agar and sabouraud agar plates in order to evaluate
their antimicrobial activity against 16 indicator bacteria, 14 filamentous fungi
and six yeasts isolates, both reference and field strains. After these screening,
culture supernatant of 17 isolates was prepared. Twenty-five Paenibacillus
isolates presented antimicrobial activity, where seven species (Paenibacillus
chibensis; P. koreensis; P. illinoiensis; P. validu; P. pabuli; P. brasilensis
and P. peoriae) stood out inhibiting at least 13 of the 16 indicator bacteria.
Only 14 of the 55 isolates exhibited antifungal activity. P. peoriae inhibited 13
among the 14 filamentous fungi and all yeasts indicator strains. Fourteen
isolates produced culture supernatant with antimicrobial activity. CONCLUSIONS:
Among the 55 isolates analysed, 25 exhibited a broad inhibition spectrum against
bacteria and pathogenic fungi. P. validus, P. chibensis, P. koreensis and P.
peoriae isolates proved to be the subject matter for studies on the production of
antimicrobial agents. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study
revealed other two species with antimicrobial activity: P. validus and P.
chibensis, and it contributed to enhance Paenibacillus biocontrolling potential,
proving that it exhibit a broad action spectrum.
PMID- 17032230
TI - Optimization of culture conditions for production of antimalarial menisporopsin A
by the seed fungus Menisporopsis theobromae BCC 4162.
AB - AIMS: The aim of this work was to optimize the production of a novel antimaralial
menisporopsin A by the seed fungus Menisporopsis theobromae BCC 4162. METHODS AND
RESULTS: Fungal cultures were grown in shake flasks at 25 degrees C in the basal
medium with varying carbon and nitrogen sources, aeration rates and initial pH
levels. The optimal carbon and nitrogen sources that improved the production of
menisporopsin A were 1% fructose and 2.5% meat extract respectively. The
production was further enhanced when the culture incubated on a shaker at 200 rev
min(-1) with an initial pH of 8. The yield of menisporopsin A cultured under the
optimized conditions was increased from 348.30 (obtained from basal medium) to
889.02 mg l(-1), and the cultivation time was reduced from 28 to only 4 days. As
a result, the productivity of menisporopsin A was greatly enhanced to 222.26 mg
l(-1) day(-1) which is 18-fold higher than that of basal conditions. Larger scale
production in a fermenter was also achieved, yielding menisporopsin A at a
maximal level of 594.32 mg l(-1) in 4 days. CONCLUSIONS: The optimized culture
conditions for menisporopsin A production by M. theobromae BCC 4162 was the
cultivation under shaking or agitation at 25 degrees C in fructose-meat extract
medium with an initial pH of 8. SIGNIFICANCE AND IMPACT OF THE STUDY: The
production of menisporopsin A in a fermenter with a relatively short incubation
period could be valuable for further utilization for chemical structure
modification and derivatization.
PMID- 17032231
TI - Prevalence and lineages of Listeria monocytogenes in Chinese food products.
AB - AIMS: This study was undertaken to investigate the prevalence and lineages of
Listeria monocytogenes in different kinds of food products in local Chinese
markets. METHODS AND RESULTS: A total of 2686 food samples and 645 water samples
were collected and L. monocytogenes was isolated from 2.28% (76 of 3331) of all
samples. The prevalence of L. monocytogenes (14 of 290, 4.83%) in raw meat
products was significantly higher than that in other raw food products (P <
0.05). Among 844 ready-to-eat (RTE) food samples, 21 samples were positive for L.
monocytogenes. RTE packaged food products from two supermarkets had a prevalence
ranging from 0.00% to 25.00%. The prevalence of L. monocytogenes in meat products
of freshly slaughtered hogs was 0.95% (four of 420), significantly lower than
that in raw meat products in the retail markets (P < 0.05). Ten isolates were
recovered from 645 water samples, which were collected after hands washing by
shopkeepers or waiters. A total of 38 isolates were randomly selected for lineage
classification based on the nucleotide variation of actA gene. Eighty percentage
of isolates from RTE food products belonged to Lineage II while only 20% belonged
to Lineage I. CONCLUSIONS: Food products in Chinese markets are contaminated with
L. monocytogenes. Raw meat products have the highest contamination rates among
all the raw food samples. RTE food products are more likely to be contaminated
with Lineage II strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The data presented
here show the main contamination sources of L. monocytogenes in Chinese food
products.
PMID- 17032232
TI - Antimicrobial resistance profiling and fla-typing of Irish thermophillic
Campylobacter spp. of human and poultry origin.
AB - AIMS: To determine the genetic relationship between a random collection of Irish
human and poultry Campylobacter isolates and to determine the frequency of
antibiotic resistance. METHODS AND RESULTS: Sixty-six Campylobacter isolates (34
human and 32 poultry) were typed by restriction fragment length polymorphism of
flagellin-A (flaA) PCR products (flaA-RFLP) and by sequencing of the short
variable region of flaA (flaA-SVR). FlaA-RFLP identified 58 distinct profiles,
while flaA-SVR identified 28 different alleles. The highest level of antibiotic
resistance was found for ampicillin (48.5%) followed by nalidixic acid (42.2%)
and ciprofloxacin (31.8%). In general, poultry isolates displayed a higher
incidence of resistance to the antimicrobials tested than the human isolates.
CONCLUSIONS: A high level of genetic diversity existed among the Campylobacter
strains confirming the weak clonality of this species. There was no relationship
between antimicrobial resistance and specific genotypes determined by flaA typing
suggesting that resistance was due to pressures of antimicrobial therapy.
SIGNIFICANCE AND IMPACT OF THE STUDY: This study emphasizes the need for
increased surveillance of antimicrobial susceptibility among Campylobacter
isolates in Ireland and the implementation of more stringent control policies
relating to the use of antimicrobials in the poultry industry.
PMID- 17032233
TI - Phenotypic and molecular typing of Vibrio harveyi isolates and their
pathogenicity to tiger shrimp larvae.
AB - AIMS: The objective of the present study was to identify the biotype(s) and
molecular type(s) of Vibrio harveyi associated with pathogenicity in tiger shrimp
(Penaeus monodon) larvae. METHODS AND RESULTS: Five luminescent and four
nonluminescent V. harveyi isolates were subjected to phenotyping and random
amplified polymorphic DNA (RAPD) fingerprinting, and pathogenicity testing to P.
monodon mysis. Four isolates induced 34-41% mortality of P. monodon mysis when
challenged at the rate of 10(6) CFU ml(-1) within 60 h. Sucrose-fermenting
biotypes of V. harveyi appeared to be associated with pathogenicity to larval
shrimp. Higher temperature and salinity appeared to play a role on the onset of
vibriosis and mortality in the challenged larval shrimp. Pathogenic isolates of
V. harveyi could be demarcated as revealed by their clustering in the dendrogram
constructed based on the RAPD fingerprints. CONCLUSIONS: Nonluminescent V.
harveyi also appear to be important aetiological agents of vibriosis of shrimp
larvae. Sucrose-fermenting biotypes are likely to be pathogenic. High temperature
may trigger onset of vibriosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Biotyping
of V. harveyi isolates and looking for traits, such as ability to ferment sucrose
may be helpful in identifying the pathogenic forms, and such approach requires to
be investigated further with larger number of isolates.
PMID- 17032234
TI - Isolation and characterization of exopolysaccharide produced by Vibrio harveyi
strain VB23.
AB - AIMS: The aim of the study was to isolate and characterize exopolysaccharide
(EPS) produced by Vibrio harveyi strain VB23. METHODS AND RESULTS: Growth and EPS
production by V. harveyi strain VB23, was studied in mineral salts medium
supplemented with NaCl (1.5%) and glucose (0.2%). The rate of EPS production in
batch cultures was highest during the late log phase of growth when compared with
stationary growth phase. The exopolymer was recovered from the culture
supernatant by using a cold ethanol precipitation-dialysis procedure. Chemical
analyses of EPS revealed that it is primarily composed of neutral sugars, uronic
acids, proteins and sulfates. The purified EPS revealed prominent functional
reactive groups, such as hydroxyl, carboxylic and amides, which correspond to a
typical heteropolymeric polysaccharide and the EPS, also possessed good
emulsification activity. The gas chromatographic analysis of an alditol acetate
derivatized sample of EPS revealed that it is composed primarily of galactose and
glucose. Minor components found were rhamnose, fucose, ribose, arabinose, xylose
and mannose. CONCLUSIONS: The EPS produced by V. harveyi strain VB23 is a
heteropolysaccharide possessing good emulsification activity. EPS was readily
isolated from culture supernatants, which suggests that the EPS was a slime-like
EPS. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of EPS
characterization in luminous V. harveyi bacteria, which describes the isolation
and characterization of an EPS expressed by V. harveyi. The results of the study
contributes significantly towards an understanding of the chemical composition
and applications of the EPS in environmental biotechnology and bioremediation.
PMID- 17032235
TI - Detection of Lactobacillus gasseri OLL2716 strain administered with yogurt drink
in gastric mucus layer in humans.
AB - In animal models and human trials, Lactobacillus gasseri OLL2716 (LG21) strain
suppressed Helicobacter pylori colonization in the stomach. The aim of the
present study was to clarify whether orally administered LG21 strain can enter
the gastric mucus layer. Biopsy samples were taken from the gastric antrum and
corpus of two healthy volunteers (H. pylori infected and non-infected) who drank
yogurt supplemented with LG21 strains. DNA of LG21 and H. pylori in the mucus
layer was detected using the laser-assisted microdissection and non-contact
pressure catapulting (LMPC) method and the semi-nested PCR method with primer
sets of RNA helicases of superfamily II gene-Insertion sequence for LG21 strain
and those of ureA gene for H. pylori. In the volunteer with H. pylori infection,
DNA fragments of LG21- and H. pylori-specific regions from both antrum and corpus
were amplified, whereas in a non-infected volunteer, only the LG21 DNA from the
antrum was amplified. The present study demonstrated that LG21 strains
administered through a yogurt drink can enter into the gastric mucus layer. Our
novel method may be useful in studying gastric probiotics for H. pylori
infection.
PMID- 17032237
TI - Influence of high-fat feeding on both naive and antigen-experienced T-cell immune
response in DO10.11 mice.
AB - Obesity is becoming one of the most serious public health problems in
industrialized societies, due to the profound changes in lifestyle, and notably
in nutrition. Beside diabetes, cardiovascular diseases or hypertension, increased
susceptibility to infection is one of the pathological consequences of being
overweight. In this paper, we have assessed the influence of a high-fat diet
(HFD) rich in saturated fatty acids on the immune system of DO11.10 mice, which
are transgenic for a T-cell receptor specifically recognizing a peptide of
ovalbumin. We showed that the specific T-cell immune response was impaired by
high-fat feeding, and that the expression of this defect is different depending
on whether T cells are naive or Ag experienced. Indeed, on in vitro ovalbumin
stimulation, spleen T cells from naive HFD-fed transgenic mice showed
proliferation similar to that of cells from standard diet (SD)-fed mice, but
exhibited a strong inflammatory profile as shown by the markedly increased IFN
gamma/IL-4 ratio. Inversely, spleen T cells from ovalbumin-immunized HFD mice
were impaired in their Ag-dependent proliferation compared to cells from SD mice.
By co-culture experiments, we showed that both T cells and antigen-presenting
cells were involved in this impairment. Moreover, in ovalbumin-immunized HFD
animals, a trend towards Th2 response was noted, compared to immunized SD mice.
This data implies that naive T cells could participate actively in the low-grade
systemic inflammation observed in overweight patients. Moreover, the impaired
activity of Ag-experienced T cells could have major consequences both in defence
against infection and/or in vaccination protocols.
PMID- 17032238
TI - Impact of influenza vaccine formulation with a detailed analysis of the cytokine
response.
AB - Vaccination provides the most effective method of limiting the impact of
influenza. Inactivated influenza vaccines are available in three formulations and
more information needs to be generated on how antigen presented in different
vaccine formulations influences the subsequent immune response. In the present
study, we have investigated the effect of two different influenza vaccine
formulations on the resulting antibody and cytokine responses and compared these
responses with influenza infection. Mice were vaccinated intramuscularly with one
or two doses of whole or split virus vaccine or alternatively intranasally
infected with influenza virus. Lymphocytes were isolated from spleen cells and
stimulated in vitro for 24 or 72 h for analysis of cytokine profile at the gene
expression and at the protein level. Additionally, whole blood was collected and
the serum antibody response investigated by haemagglutination inhibition (HI) and
enzyme-linked immunosorbent assay (ELISA). We found that one dose of whole virus
vaccine induced higher antibody and cytokine responses and thus was more
immunogenic in unprimed mice than split virus vaccine. Whole virus vaccine
induced a strong IFN-gamma (type 1) immune response after one dose of vaccine and
a more mixed cytokine response after the second dose. Split virus vaccine induced
a type 2 response, particularly after two vaccine doses. Our results show that
two doses of vaccine (both vaccine formulation) were more effective in induction
of Th2 type of cytokines and thus indicate that both the formulation and also the
number of vaccine doses substantially influences the magnitude and quality of the
immune response.
PMID- 17032239
TI - Chimaeric protein improved immunogenicity compared with fusion protein of Ag85B
and ESAT-6 antigens of Mycobacterium tuberculosis.
AB - Antigen 85B (Ag85B) and ESAT-6 are important immunodominant antigens of
Mycobacterium tuberculosis, and both are very promising vaccine candidate
molecules. In this study, we relied on the T-cell epitopes of Ag85B and ESAT-6 to
design a chimaeric protein by inserting ESAT-6 into Ag85B from the amino acids
167-182. We found the ratio of IgG2b/IgG1 and the secretion of interferon (IFN)
gamma in the mice vaccinated with the new protein with adjuvant MPL and TDM were
higher than the mice immunized with fusion protein Ag85B-ESAT-6, which have been
reported and could induce levels of protective immunity similar to BCG in the
mouse model of tuberculosis (TB) infection. These results suggest that the
chimaeric protein Ag85B(N)-ESAT-6-Ag85B(C) is a strong candidate for further
study and the T-cell epitopes of the antigens should be considered when we design
the subunit vaccine.
PMID- 17032240
TI - B-cell CD25 expression in murine primary and secondary lymphoid tissue.
AB - B cells are in analogy with T cells capable of expressing functional IL-2
receptors. IL-2R alpha-chain (CD25) positive T cells have been studied in detail
but not much is known about CD25 positive B cells. The aim of this study was to
examine the phenotypic properties of the CD25 expressing B cells collected from
different lymphoid organs in mice. Samples were stained for various cell surface
markers and analysed using flow cytometry. We found that approximately 49% of B
cells in bone marrow, 16% in peritoneal cavity, 2% in spleen and 1% in lymph
nodes express CD25. In contrast, CD25 expressing B cells were not found in the
blood or in Peyer's patches. Phenotypic characterization showed that CD25+ B
cells in spleen, lymph nodes and peritoneal cavity have higher expression of
AA4.1, CD5, CD69, CD80, CD86, CD122, CD132, IgA, IgG and IgM on their surface in
comparison with CD25- B cells. In contrast, expression of IgD and IA-IE was lower
on CD25+ B cells in spleen and lymph nodes. In bone marrow, the expression of
CD5, CD80, CD86, CD122, CD132, IgA, IgD and IgM was lower, while the expression
of AA4.1, IgG and IA-IE was increased on CD25+ B cells compared with CD25- B
cells. In conclusion, our results indicate that B cells expressing CD25 are
phenotypically distinctly different from those that are CD25 negative. Our
findings suggest that CD25+ B cells are more prone to efficient antigen
presentation and display a more mature phenotype.
PMID- 17032241
TI - Dendritic cells therapy confers a protective microenvironment in murine
pregnancy.
AB - The fetal-placental unit is a semi-allograft and immunological recognition of
pregnancy, together with the subsequent response of the maternal immune system,
is necessary for a successful pregnancy. Dendritic cells (DC) show a biological
plasticity that confers them special characteristics regulating both immunity and
tolerance. Therapy employing DC proved to diminish the abortion in the DBA/2J
mated CBA/J females; however, the underlying mechanisms remain unknown. Here, we
evaluated whether DC therapy influences the presence of immunoregulatory
populations of cells at the fetal-maternal interface. To address this hypothesis,
we analysed the pregnancy-protective CD8, gammadelta cell populations as well as
transforming growth factor (TGF)-beta1 and progesterone-induced blocking factor
(PIBF) expression at the fetal-maternal interface from abortion-prone female mice
that had previously received adoptive transfer of syngeneic DC. Syngeneic DC
therapy induced an increase in the number of CD8 and gammadelta cells.
Additionally, an upregulation of TGF-beta1 and PIBF expression could be detected
after DC transfer. We suggest that DC therapy differentially upregulates a
regulatory/protective population of cells at the fetal-maternal interface. It is
reasonable to assure that this mechanism would be responsible for the lower
abortion rate.
PMID- 17032242
TI - Regulatory activity of activated murine peripheral CD4+CD25- T cells: a possible
mechanism of feedback regulation on adaptive immunity.
AB - This study was undertaken to investigate the possibility that peripheral CD4+CD25
T cells, once fully activated, transiently obtain suppressive function against
other T cells. CD4+CD25- T cells, isolated from splenocytes of BALB/c mice, were
stimulated with anti-CD3 MoAb in the presence of feeder cells for 72 h. The
activated CD4+ T cells (T(act)) thus obtained were able to inhibit the activation
and proliferation of bystander CD4+ T cells in a non-MHC-restricted manner.
T(act)-mediated suppression was cell contact dependent, reversible by exogenous
IL-2 as well as anti-GITR antibody. Furthermore, adoptive transfer of T(act)
cells significantly downregulated humoral response of BALB/c mice to s.c.
immunization with ovalbumin. We argue that suppression mediated by activated
CD4+CD25- T cells may play an important role in maintaining homeostasis of the
immune system and preventing excessive T-cell responses in vivo.
PMID- 17032243
TI - Measurement and significance of 3-nitrotyrosine in systemic lupus erythematosus.
AB - Nitration of free and protein associated tyrosine represents, in vivo, a
mechanism that can severely compromise the cell function. The detection of 3
nitrotyrosine (3-NT) in pathological tissues is suggestive of the occurrence of
nitrating pathways and has been identified as a marker of inflammation and a
stable end product of increased reactive nitrogen intermediate production.
Protein nitration occurs in many disease conditions including systemic lupus
erythematosus (SLE). In this study we show that the level of both free and
protein bound 3-NT, which is produced by reactive nitrogen species (RNS)
dependent oxidative damage, is elevated in patients with SLE and that there is a
possible role of RNS-modified epitopes in the aetiology of the disease.
Commercially available poly L-tyrosine was exposed to nitrating species, inducing
nitration in tyrosine residues. Immunoglobulin-G (IgG) purified on Protein-A
Sepharose matrix from 24 SLE patients was studied for their recognition of native
and nitrated poly L-tyrosine by direct binding and competition enzyme-linked
immunosorbent assay (ELISA). The formation of immune complex between SLE IgG and
nitrated poly L-tyrosine was visualized by gel retardation assay. Free 3-NT in
patients' sera was detected and quantitated by high performance liquid
chromatography whereas protein-bound 3-NT was analysed by Western blotting and
the concentration was calculated by sandwich ELISA. The concentration of free 3
NT was found to be 1.4 +/- 0.09 microm whereas the concentration of protein bound
3-NT was 96.52 +/- 21.12 microm nitrated bovine serum albumin equivalents/mg
protein, which was significantly higher when compared with healthy controls.
Elevated level of 3-NT was observed in SLE patients using two different
techniques, when compared with healthy subjects confirms the overproduction of
RNS in the pathogenesis of human SLE.
PMID- 17032244
TI - Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion
in rheumatoid arthritis.
AB - Interleukin (IL)-21 is a CD4+ T-cell-derived cytokine, which is involved in
innate and adaptive immune response. In this study, we analysed IL-21 receptor
(IL-21R) expression in peripheral blood and synovial fluid mononuclear cells, and
investigated the role of IL-21 in the induction of proinflammatory cytokine
production by peripheral blood T cells (PB-T) and synovial fluid T cells (SF-T)
from patients with rheumatoid arthritis (RA). Immunohistochemical staining
demonstrated that IL-21R-positive cells were significantly increased in inflamed
synovial tissues of RA patients compared with osteoarthritis (OA) and healthy
controls. Flow cytometric analysis confirmed that IL-21R was mainly expressed in
freshly isolated CD4, CD8, B and NK cells from peripheral blood and synovial
fluid, but decreased gradually in T cells 24 h after anti-CD3 stimulation. PB-
and SF-T cells from RA patients were more responsive to IL-21 when compared with
controls. Importantly, isolated PB- or SF-T cells from RA patients, when
stimulated with IL-21 and anti-CD3 MoAb, secreted markedly higher levels of TNF
alpha and IFN-gamma than controls. These data indicate that IL-21R is
overexpressed in the inflamed synovial membrane and in peripheral blood or
synovial fluid leukocytes of RA patients, and that IL-21 enhances local T-cell
activation, proliferation and proinflammatory cytokine secretion. Thus, blockade
of IL-21R signalling pathway may have a therapeutic potential in acute RA
patients.
PMID- 17032245
TI - Dysregulation of TNF/TNFR superfamily members: a systemic link between intra- and
extrathyroidal manifestations in Graves' disease.
AB - Graves' disease (GD) coincides with the occurrence of disease-associated
intrathyroidal dendritic cells (DC) and intraorbital inflammatory macrophages
(Mphi). Physiologically, tumour necrosis factor-alpha (TNF-alpha) strongly
affects the differentiation of DC and Mphi from monocytic precursors; we thus
hypothesized that dysregulation of the TNF/TNFR superfamilies may provide a
systemic pathogenic link in GD. In patients without eye symptoms, percentages of
TNF-alpha-stimulated blood monocytes were highly significantly (P < 0.001)
elevated, corresponding to both intrathyroidal DC maturation as well as increases
in mature blood DC (MHC-II(hi)/CD40+/RFD1(hi)) and B cells (CD20(hi)/CD40+). GD
patients also displaying eye symptoms revealed a striking reduction in blood
monocytes, yet significantly (P < 0.05) increased CD40(hi) and TNF-alpha(hi)
leucocytes. These findings suggest for GD that excess TNF-alpha induces monocytes
to differentiate into hyperactivated thyroidal DC that, once emigrated, initiate
systemic humoral autoimmunity associated with CD40/TNF-alpha upregulation. Such
overexpression may instigate differentiation of periorbital inflammatory Mphi
from CD14(hi)/CD16+ monocytes as a likely precursor subset. These results
indicate that dysregulation of TNF/TNFR superfamily members provides a systemic
pathogenic link in GD in that hyperactivated circulating monocytic precursors
give rise to locally restricted, disease-associated DC and Mphi. Monocytes,
therefore, may serve as a suitable target to therapeutically address the common
precursor of key promoters of GD.
PMID- 17032246
TI - Immune regulatory T cells in siblings of children suffering from type 1 diabetes
mellitus.
AB - Patients with type 1 diabetes are suffering from defects in immune regulatory
cells. Their siblings may be at increased risk of type 1 diabetes especially if
they are carriers of certain human leucocyte antigen (HLA) alleles. In a
prospective non-randomized study, we intended to evaluate 31 healthy siblings of
paediatric patients with type 1 diabetes and explore immune regulatory
populations of CD4+CD25+ T cells and natural killer (NK) T cells. Tested siblings
of type 1 diabetes patients were stratified according to the HLA-associated risk
of possible diabetes development. Immune regulatory function of CD4+CD25+ T cells
was tested in vitro. Significant differences in CD4+CD25+ but not in NK T cells
have been identified. Siblings of type 1 diabetes patients carrying high risk HLA
alleles (DQA1*05, DQB1*0201, DQB1*0302) had significantly lower number of immune
regulatory CD4+CD25+ T cells than the age-matched healthy controls or siblings
carrying low-risk HLA alleles (DQB1*0301, DQB1*0603, DQB1*0602). Regulatory
function of CD4+CD25+ T cells demonstrated a dose-escalation effect. In siblings
of type 1 diabetes patients, the defect in immune regulatory CD4+CD25+ T cells
exists in association with genetic HLA-linked risk for type 1 diabetes.
PMID- 17032247
TI - Frequency analysis of HBsAg-specific B lymphocytes in high-responder individuals
to recombinant hepatitis B vaccine: comparison of LDA and ELISPOT assays.
AB - The determination of the frequency of antigen-specific lymphocytes may provide
invaluable information for the evaluation of the immune response to different
antigens and pathogens. Different methods are employed to determine the frequency
of specific B lymphocytes in peripheral blood. In this study, the frequency of
hepatitis B surface antigen (HBsAg)-specific B lymphocytes was determined by a
limiting dilution assay (LDA) and an enzyme-linked immunospot assay (ELISPOT) in
seven healthy adult high responders to recombinant HBsAg. Peripheral blood
mononuclear cells isolated at different time intervals (1, 2, 4, 8 and 16 weeks)
following administration of a booster dose were either transformed with Epstein
Barr virus (LDA) or stimulated with Pokeweed mitogen (ELISPOT). In an LDA, anti
HBs positive wells were screened by a sandwich ELISA and the frequency of
specific B lymphocytes was estimated based on the Poisson statistical analysis.
In an ELISPOT, coloured spots representing specific B lymphocytes were finally
enumerated by stereomicroscope. Our results showed a significant increase in the
number of specific B lymphocytes in the first week by an ELISPOT compared with an
LDA (1:190 versus 1:13,462) (P < 0.001). No significant differences were observed
at other time intervals. A significant correlation was observed between the serum
titer of anti-HBs antibody and frequency of HBsAg-specific B cells obtained by
LDA and ELISPOT methods at different time intervals. The highest correlation was
found at fourth week in LDA (r = 0.83, P < 0.01) and ELISPOT (r = 0.85, P < 0.01)
assays. Furthermore, a significant correlation was observed between an LDA and
ELISPOT at different time intervals (highest correlation in second week, r =
0.88, P < 0.008). These findings suggest that in addition to technical
advantages, such as speed and simplicity, an ELISPOT is a more sensitive assay,
compared with an LDA.
PMID- 17032248
TI - Anti-TNF effects on destructive fibroblasts depend on mechanical stress.
AB - Joint destruction in rheumatoid arthritis (RA) starts typically at sites of
mechanically stressed inserts of the synovial membrane near the cartilage/bone
border. In the therapy of RA, tumour necrosis factor (TNF) antagonists have
rapidly emerged as a valuable class of anti-rheumatic agents that reduce joint
destruction. The aim of this study was to investigate and profile genes involved
in the interaction between articular movement and anti-TNF therapy in an in vitro
model. Murine LS48 cells, an established substitute for invasive RA synovial
fibroblasts, were cultured, stretched and/or treated with anti-TNF-alpha antibody
for 24 h. RNA was isolated and gene transcript levels were determined using
U74Av2 Affymetrix GeneChips to identify transcriptional events. Positive findings
were verified by polymerase chain reaction (PCR). We identified 170
differentially regulated genes, including 44 of particular interest. Gene
expression fell into different functional groups that can be explained by RA
pathogenesis and experimental conditions. For 21 genes of the 44 of particular
interest, regulation could be confirmed by real-time PCR. Remarkably, we found
structural as well as functional genes differently regulated between stretched
cells, anti-TNF-treated cells, and stretched cells treated with anti-TNF
antibody. Additionally, we also found a large number of genes that are apparently
not related to the experimental conditions. Mechanical exertion modulates gene
expression and subsequently cellular response to anti-TNF therapy. Results in
exerted cells correspond to current knowledge regarding RA pathogenesis and
underline the relevance of our experimental approach. Finally, the central
function of the interleukin-18 system in joint destruction could be confirmed by
our findings.
PMID- 17032249
TI - Benznidazole treatment during early-indeterminate Chagas' disease shifted the
cytokine expression by innate and adaptive immunity cells toward a type 1
modulated immune profile.
AB - Trypanosoma cruzi-infected children was treated with benznidazole (Bz) during the
early-indeterminate disease (E-IND) and the cytokine pattern of innate and
adaptive immune compartments were evaluated prior to the treatment and 1 year
after it. At first, we observed that the ex vivo cytokine profile of circulating
leukocytes from E-IND (n = 6) resembled the one observed for healthy
schoolchildren (n = 7). Additionally, in vitro stimulation with T. cruzi antigens
drove the E-IND cytokine pattern toward a mixed immune profile with higher levels
of IFN-gamma+, TNF-alpha+ and IL-4+ NK cells, increased numbers of IFN-gamma+,
TNF-alpha+ and IL-10+ CD4+ T cells in addition to enhanced frequency of TNF
alpha+/IL-4+ CD19+ lymphocytes. Interestingly, upon T. cruzi antigen in vitro
stimulation, E-IND CD8+ lymphocytes displayed a selective enhancement of IFN
gamma expression, accounting for a global type 1-modulated cytokine
microenvironment. A shift toward a type 1-modulated profile was also the hallmark
of Bz-treated children (E-IND(T)). In this context, despite the mixed overall ex
vivo cytokine profile observed for NK and CD8+ T cells, increased ability of
these leukocytes to produce IFN-gamma in response to T. cruzi antigens was
reported. Most noteworthy was the IL-10 production evidenced at T lymphocytes,
mainly CD4+ cells, as well as B lymphocytes, both ex vivo and upon antigen
stimulation. Together, these findings gave evidence that NK cells and CD8+ T
lymphocytes are the major sources of IFN-gamma, a pivotal cytokine for successful
therapeutic response in human Chagas' disease. Moreover, our data have also
brought additional information, pointing out IL-10 production by CD4+ cells and B
lymphocytes, as the putative key element for parasite clearance in the absence of
deleterious tissue damage.
PMID- 17032250
TI - Preparation, characterization and epitope mapping of monoclonal antibodies
specific to human mast cell carboxypeptidase.
AB - Human mast cell carboxypeptidase (hMC-CP) is a unique product of mast cells.
Unlike tryptase and chymase, its potential function and expression in diseased
conditions remain largely unknown. To develop an assay for hMC-CP, the
recombinant fusion protein of hMC-CP and purified native skin hMC-CP was
prepared, and two novel monoclonal antibodies against hMC-CP named CCP1 (IgG1
isotype) and CCP2 (IgM isotype) were raised in the present study. Epitope
analysis shows that CCP1 and CCP2 antibodies recognize epitopes located in the
region of amino acids 112-202 of hMC-CP, and hydrophilicity analysis implies that
epitopes might be located in the amino acid residues 123-134 and 165-177.
Furthermore, using a competition enzyme-linked immunosorbent assay, it was shown
that the epitope recognized by CCP1 is close to that recognized by CCP2 or the
two antibodies partially share the same epitope. Flow cytometry analysis shows
that basophilic leukemia cell line KU812 reacts with both CCP1 and CCP2
antibodies, suggesting that this cell line expresses hMC-CP. In conclusion,
although the two antibodies possess different isotypes, they may partially share
the same epitope. These two antibodies will be valuable tools for the development
of an assay to detect the levels of hMC-CP in the biological fluids in man.
PMID- 17032251
TI - Modulation of chemokine gene expression in CD133+ cord blood-derived human mast
cells by cyclosporin A and dexamethasone.
AB - We have recently developed a protocol for generating huge numbers of mature and
functional mast cells from in vitro differentiated umbilical cord blood cells.
Using CD133 as a positive selection marker to isolate haematopoietic progenitors
we routinely expand the number of recovered cells at least 150-fold, which vastly
exceeds the yields of conventional protocols using CD34+ cells as a source of
progenitors. Taking advantage of the large quantities of in vitro differentiated
mast cells, here we assess at the levels of transcription and translation the
kinetics of chemokine gene induction following receptor mediated mast cell
activation or following pharmacological activation of specific signal
transduction cascades that become activated upon classical FcepsilonRI receptor
crosslinking. We demonstrate that chemokine genes encoding IL-8, MCP-1, MIP
1alpha, and MIP-1beta are induced with different kinetics and with different
amplitudes in a receptor activation dependent manner, and that these events can
be mimicked using pharmacological agents which activate distinct signal
transduction pathways. These findings were corroborated by adding
immunomodulators such as cyclosporin A and dexamethasone prior to mast cell
activation. Finally, we demonstrate that the same modulators added after mast
cell activation can differentially quench ongoing chemokine gene induction. Thus,
considering the vast yields of mast cells, our protocol is valuable not only for
studying regulation of gene expression in mast cells in general, but also as an
experimental tool to develop better and more balanced treatments of mast cell
related disorders.
PMID- 17032252
TI - Phytochrome-mediated development in land plants: red light sensing evolves to
meet the challenges of changing light environments.
AB - Phytochromes are photoreceptors that provide plants with circadian, seasonal, and
positional information critical for the control of germination, seedling
development, shade avoidance, reproduction, dormancy, and sleep movements.
Phytochromes are unique among photoreceptors in their capacity to interconvert
between a red-absorbing form (absorption maximum of approximately 660 nm) and a
far-red absorbing form (absorption maximum of approximately 730 nm), which occur
in a dynamic equilibrium within plant cells, corresponding to the proportions of
red and far-red energy in ambient light. Because pigments in stems and leaves
absorb wavelengths below about 700 nm, this provides plants with an elegant
system for detecting their position relative to other plants, with which the
plants compete for light. Certain aspects of phytochrome-mediated development
outside of flowering plants are strikingly similar to those that have been
characterized in Arabidopsis thaliana and other angiosperms. However, early
diverging land plants have fewer distinct phytochrome gene lineages, suggesting
that both diversification and subfunctionalization have been important in the
evolution of the phytochrome gene family. There is evidence that
subfunctionalization proceeded by the partitioning among paralogues of
photosensory specificity, physiological response modes, and light-regulated gene
expression and protein stability. Parallel events of duplication and functional
divergence may have coincided with the evolution of canopy shade and the
increasing complexity of the light environment. Within angiosperms, patterns of
functional divergence are clade-specific and the roles of phytochromes in A.
thaliana change across environments, attesting to the evolutionary flexibility
and contemporaneous plasticity of phytochrome signalling in the control of
development.
PMID- 17032253
TI - Blind population genetics survey of tropical rainforest trees.
AB - Rainforest tree species can be difficult to identify outside of their period of
reproduction. Vascular tissues from Carapa spp. individuals were collected during
a short field trip in French Guiana and analysed in the laboratory with nuclear
and chloroplast markers. Using a Bayesian approach, > 90% of the samples could be
assigned to one of two distinct clusters corresponding to previously described
species, making it possible to estimate the genetic structure of each species and
to identify cases of introgression. We argue that this blind procedure represents
a first-choice rather than a fallback option whenever related taxa are
investigated.
PMID- 17032254
TI - Genetic structure at range edge: low diversity and high inbreeding in Southeast
Asian mangrove (Avicennia marina) populations.
AB - Understanding the genetic composition and mating systems of edge populations
provides important insights into the environmental and demographic factors
shaping species' distribution ranges. We analysed samples of the mangrove
Avicennia marina from Vietnam, northern Philippines and Australia, with
microsatellite markers. We compared genetic diversity and structure in edge
(Southeast Asia, and Southern Australia) and core (North and Eastern Australia)
populations, and also compared our results with previously published data from
core and southern edge populations. Comparisons highlighted significantly reduced
gene diversity and higher genetic structure in both margins compared to core
populations, which can be attributed to very low effective population size,
pollinator scarcity and high environmental pressure at distribution margins. The
estimated level of inbreeding was significantly higher in northeastern
populations compared to core and southern populations. This suggests that despite
the high genetic load usually associated with inbreeding, inbreeding or even
selfing may be advantageous in margin habitats due to the possible advantages of
reproductive assurance, or local adaptation. The very high level of genetic
structure and inbreeding show that populations of A. marina are functioning as
independent evolutionary units more than as components of a metapopulation system
connected by gene flow. The combinations of those characteristics make these
peripheral populations likely to develop local adaptations and therefore to be of
particular interest for conservation strategies as well as for adaptation to
possible future environmental changes.
PMID- 17032255
TI - Population structure within and between subspecies of the Mediterranean triplefin
fish Tripterygion delaisi revealed by highly polymorphic microsatellite loci.
AB - Although F(ST) values are widely used to elucidate population relationships, in
some cases, when employing highly polymorphic loci, they should be regarded with
caution, particularly when subspecies are under consideration. Tripterygion
delaisi presents two subspecies that were investigated here, using 10
microsatellite loci. A Bayesian approach allowed us to clearly identify both
subspecies as two different evolutionary significant units. However, low F(ST)
values were found between subspecies as a consequence of the large number of
alleles per locus, while homoplasy could be disregarded as indicated by the
standardized genetic distance G'(ST). Heterozygosity saturation was observed in
highly polymorphic loci containing more than 15 alleles, and this threshold was
used to define two loci pools. The less variable loci pool revealed higher
genetic variance between subspecies, while the more variable pool showed higher
genetic variance between populations. Furthermore, higher differentiation was
also observed between populations using G'(ST) with the more variable loci.
Nonetheless, a more reliable population structure within subspecies was obtained
when all loci were included in the analyses. In T. d. xanthosoma, isolation by
distance was detected between the eight analysed populations, and six genetically
homogeneous clusters were inferred by Bayesian analyses that are in accordance
with F(ST) values. The neighbourhood-size method also indicated rather small
dispersal capabilities. In conclusion, in fish with limited adult and larval
dispersal capabilities, continuous rocky habitat seems to allow contact between
populations and prevent genetic differentiation, while large discontinuities of
sand or deep-water channels seems to reduce gene flow.
PMID- 17032256
TI - Evolutionary diversification of the bean beetle genus Callosobruchus (Coleoptera:
Bruchidae): traits associated with stored-product pest status.
AB - Despite the fact that many plant-feeding insects are pests, little effort has
been made to identify key evolutionary trait transitions that allow taxa to
acquire or lose pest status. A large proportion of species in the genus
Callosobruchus are economically important pests of stored, dry postharvest beans
of the tribe Phaseoleae. However, the evolution of this feeding habit is poorly
understood. Here, we present a reconstruction of the phylogeny of the Asian and
African Callosobruchus based on three mitochondrial genes, and assess which
traits have been associated with the evolutionary origin or loss of ability to
reproduce on dry beans. Our phylogenetic analysis showed that species group into
the chinensis and the maculatus clades, which are also supported by genital
morphology, and an additional paraphyletic group. Ancestral ability to use dry
beans has been lost in the chinensis clade but acquired again in C. chinensis.
Dry-bean use and host-plant use were both phylogenetically constrained and
transitions in the two were significantly correlated. Host shifts from the
subtribe Phaseolinae to Cajaninae were more common than the reverse and were more
likely in species using young beans. The ability to use dry beans was more likely
gained when using Phaseolinae hosts and promoted habitat shifts from tropical to
temperate regions. Adaptation to arid climate was also associated with the
ability to reproduce on dry beans and on Phaseolinae. Thus, our analysis suggests
that physiological adaptations to an arid climate and to Phaseolinae hosts both
render beetles predisposed to become pests of cultivated beans.
PMID- 17032257
TI - Spatial population genetic structure and limited dispersal in a Rocky Mountain
alpine stream insect.
AB - Using the mitochondrial cytochrome oxidase I (COI) gene, we assessed the
phylogeographic structure of Prosimulium neomacropyga, a black fly (Simuliidae)
whose distribution in the US Southern Rockies ecoregion is limited to alpine
tundra streams. Given high habitat specificity, lack of hydrological connection
between streams, and a terrestrial environment restrictive to insect flight, we
hypothesized limited gene flow. A spatially nested sampling design showed that
grouping populations according to high-elevation 'islands' of alpine tundra
(which typically include headwater streams of > 1 watershed) explained a
significant proportion of genetic variation while grouping streams according to
major watershed (across islands) did not. Nested clade analysis and isolation-by
distance (IBD) relationships further implicated limited ongoing gene flow within
but not among the isolated alpine islands. IBD was strong among five streams
within an individual island using each of four alternative models of pairwise
landscape connectivity for flying insects. Results of all landscape models were
positively correlated, suggesting that straight-line distance is an acceptable
surrogate for presumably more biologically meaningful connectivity measures in
this system. IBD was significantly weaker across the entire study area, comprised
of three separate islands. Overall, population structure was significant with
F(ST) = 0.38, suggesting limited dispersal across a small spatial extent.
PMID- 17032259
TI - Genetic admixture of burbot (Teleostei: Lota lota) in Lake Constance from two
European glacial refugia.
AB - The burbot, Lota lota, is the only freshwater species of the codfish family and
has a Holarctic distribution. Pleistocene glaciations caused significant
geographical differentiation in the past, but its life history characterized by
winter spawning migrations over large distances is likely to homogenize
populations by contemporary gene flow. We investigated the population genetic
structure of 541 burbots from Lake Constance and adjacent Rhine and Danube
tributaries in Europe using the entire mitochondrial DNA (mtDNA) control region
and 11 microsatellites. Microsatellites revealed considerable population
divergence (F(ST) = 0.26) and evidenced recent bottlenecks in two Central
European rivers. In accordance to previous evidence two main phylogeographic
lineages (Atlantic and Danubian) were found co-occurring at similar frequencies
in Lake Constance, where they currently undergo random mating as indicated by
microsatellites. The Danubian lineage contributed only a small proportion to the
lake's mtDNA diversity, and probably expanded within the lake shortly after its
formation approximately 10,000-15,000 BP. The larger Atlantic haplotype diversity
suggested a population expansion older than the lake itself. Levels of admixture
at microsatellite loci were less obvious due to their high variability, and
coalescence methods were used to estimate past admixture proportions. Our results
reinforce a model of a two-step colonization of Europe by burbot from an
ancestral Danubian refuge, and confirm the persistence of a secondary Atlantic
refuge, as proposed to exist for other freshwater fish. We conclude that the
present-day burbot population in Lake Constance bears the genetic signature of
both contemporary gene flow and historical separation events.
PMID- 17032260
TI - Genetics of recent habitat contraction and reduction in population size: does
isolation by distance matter?
AB - Fragmentation and loss of natural habitats are recognized as major threats to
contemporary flora and fauna. Detecting past or current reductions in population
size is therefore a major aim in conservation genetics. Statistical methods
developed to this purpose have tended to ignore the effects of spatial population
structure. However in many species, individual dispersal is restricted in space
and fine-scale spatial structure such as isolation by distance (IBD) is commonly
observed in continuous populations. Using a simulation-based approach, we
investigated how comparative and single-point methods, traditionally used in a
Wright-Fisher (WF) population context for detecting population size reduction,
behave for IBD populations. We found that a complex 'quartet' of factors was
acting that includes restricted dispersal, population size (i.e. habitat size),
demographic history, and sampling scale. After habitat reduction, IBD populations
were characterized by a stronger inertia in the loss of genetic diversity than WF
populations. This inertia increases with the strength of IBD, and decreases when
the sampling scale increases. Depending on the method used to detect a population
size reduction, a local sampling can be more informative than a sample scaled to
habitat size or vice versa. However, IBD structure led in numerous cases to
incorrect inferences on population demographic history. The reanalysis of a real
microsatellite data set of skink populations from fragmented and intact
rainforest habitats confirmed most of our simulation results.
PMID- 17032261
TI - Analysis of spatial genetic structure in an expanding Pinus halepensis population
reveals development of fine-scale genetic clustering over time.
AB - We analysed the change of spatial genetic structure (SGS) of reproductive
individuals over time in an expanding Pinus halepensis population. To our
knowledge, this is the first empirical study to analyse the temporal component of
SGS by following the dynamics of successive cohorts of the same population over
time, rather than analysing different age cohorts at a single time. SGS is
influenced by various factors including restricted gene dispersal,
microenvironmental selection, mating patterns and the spatial pattern of
reproductive individuals. Several factors that affect SGS are expected to vary
over time and as adult density increases. Using air photo analysis, tree-ring
dating and molecular marker analysis we reconstructed the spread of reproductive
individuals over 30 years beginning from five initial individuals. In the early
stages, genotypes were distributed randomly in space. Over time and with
increasing density, fine-scale (< 20 m) SGS developed and the magnitude of
genetic clustering increased. The SGS was strongly affected by the initial
spatial distribution and genetic variation of the founding individuals. The
development of SGS may be explained by fine-scale environmental heterogeneity and
possibly microenvironmental selection. Inbreeding and variation in reproductive
success may have enhanced SGS magnitude over time.
PMID- 17032258
TI - Assessment of the diversity and species specificity of the mutualistic
association between Epicephala moths and Glochidion trees.
AB - The obligate mutualisms between flowering plants and their seed-parasitic
pollinators constitute fascinating examples of interspecific mutualisms, which
are often characterized by high levels of species diversity and reciprocal
species specificity. The diversification in these mutualisms has been thought to
occur through simultaneous speciation of the partners, mediated by tight
reciprocal adaptation; however, recent studies cast doubt over this general view.
In this study, we examine the diversity and species specificity of Epicephala
moths (Gracillariidae) that pollinate Glochidion trees (Phyllanthaceae), using
analysis of mitochondrial and nuclear gene sequences. Phylogenetic analysis of
Epicephala moths associated with five Glochidion species in Japan and Taiwan
reveal six genetically isolated species that are also distinguishable by male
genital morphology: (i) two species specific to single host species (G.
acuminatum and G. zeylanicum, respectively); (ii) two species that coexist on G.
lanceolatum; and (iii) two species that share two, closely-related parapatric
hosts (G. obovatum and G. rubrum). Statistical analysis shows that the two
species associated with G. lanceolatum are not sister species, indicating the
colonization of novel Glochidion host in at least one lineage. Behavioural
observations suggest that all six species possess the actively-pollinating habit,
thus none of the studied species has become a nonmutualistic 'cheater' that
exploits the benefit resulting from pollination by other species. Our results
parallel recent findings in ecologically similar associations, namely the fig-fig
wasp and yucca-yucca moth mutualisms, and contribute to a more general
understanding of the factors that determine ecological and evolutionary outcomes
in these mutualisms.
PMID- 17032262
TI - Geological history and within-island diversity: a debris avalanche and the
Tenerife lizard Gallotia galloti.
AB - Several processes have been described that could explain geographical variation
and speciation within small islands, including fragmentation of populations
through volcanic eruptions. Massive landslides, or debris avalanches, could cause
similar effects. Here we analyse the potential impact of the 0.8 million-year-ago
(Ma) Guimar valley debris avalanche on the phylogeography of the lizard Gallotia
galloti on the Canary Island of Tenerife. Distributions of mitochondrial DNA
lineages (based on cytochrome b sequences) were analysed on a 60-km southeastern
coast transect centred on this area. Three main clades were detected, which can
be divided into northern (one clade) and southern (two clades) groups that
introgress across the valley. Maximum-likelihood estimates of migration rates
(scaled for mutation rate) revealed highly asymmetric patterns, indicating that
long-term gene flow into this region from both the northern and the southern
populations greatly exceeded that in the opposite directions, consistent with
recolonization of the area. The ancestral Tenerife node on the G. galloti tree is
estimated at 0.80 Ma, matching closely with the geological estimate for the
debris avalanche. Morphological variation (body dimensions and scalation) was
also analysed and indicated a stepped cline in female scalation across the
valley, although the patterns for male scalation and male and female body
dimensions were not as clear. Together these findings provide support for the
hypothesis that the debris avalanche has shaped the phylogeography of G. galloti
and may even have been a primary cause of the within-island cladogenesis through
population fragmentation and isolation. Current estimates of timing of island
unification mean that the original hypothesis that within-island diversity is
explained by the secondary contact of populations from the two ancient precursor
islands of Teno and Anaga is less plausible for this and some other Tenerife
species. Large-scale landslides have occurred on many volcanic islands, and so
may have been instrumental in shaping within-island diversities.
PMID- 17032263
TI - Contrasting patterns in genetic diversity following multiple invasions of fresh
and brackish waters.
AB - Biological invasions may combine the genetic effects of population bottlenecks
and selection and thus provide valuable insight into the role of such processes
during novel environmental colonizations. However, these processes are also
influenced by multiple invasions, the number of individuals introduced and the
degree of similarity between source and receiving habitats. The amphipod Gammarus
tigrinus provides a useful model to assess these factors, as its invasion history
has involved major environmental transitions. This species is native to the
northwest Atlantic Ocean, although it invaded both brackish and freshwater
habitats in the British Isles after introduction more than 65 years ago. It has
also spread to similar habitats in Western Europe and, most recently, to Eastern
Europe, the Baltic Sea, and the Laurentian Great Lakes. To examine sources of
invasion and patterns of genetic change, we sampled populations from 13 native
estuaries and 19 invaded sites and sequenced 542 bp of the mitochondrial COI
gene. Strong native phylogeographical structure allowed us to unambiguously
identify three allopatrically evolved clades (2.3-3.1% divergent) in invading
populations, indicative of multiple introductions. The most divergent clades
occurred in the British Isles and mainland Europe and were sourced from the St
Lawrence and Chesapeake/Delaware Bay estuaries. A third clade was found in the
Great Lakes and sourced to the Hudson River estuary. Despite extensive sampling,
G. tigrinus did not occur in freshwater at putative source sites. Some European
populations showed reduced genetic diversity consistent with bottlenecks,
although selection effects cannot be excluded. The habitat distribution of clades
in Europe was congruent with the known invasion history of secondary spread from
the British Isles. Differences in salinity tolerance among lineages were
suggested by patterns of habitat colonization by different native COI clades.
Populations consisting of admixtures of the two invading clades were found
principally at recently invaded fresh and brackish water sites in Eastern Europe,
and were characterized by higher genetic diversity than putative source
populations. Further studies are required to determine if these represent novel
genotypes. Our results confirm that biological invasions need not result in
diminished genetic diversity, particularly if multiple source populations, each
with distinctive genetic composition, contribute to the founding populations.
PMID- 17032264
TI - Temporal cline in a hybrid zone population between Fraxinus excelsior L. and
Fraxinus angustifolia Vahl.
AB - The two closely related ash species Fraxinus excelsior L. (common ash) and
Fraxinus angustifolia Vahl (narrow-leaved ash) have a broad contact zone in
France where they hybridize. However, little is known about the local structure
of hybrid zone populations and the isolation mechanisms. We assessed the
potential effect of floral phenology on the structure of a riparian ash hybrid
zone population in central France. The distribution of flowering times was
unimodal and lay between the flowering periods of the two species. Using
microsatellite markers, we detected isolation by time, which has possibly
originated from assortative mating. Multivariate analyses indicated that
morphological variation is not distributed at random with respect to flowering
times. Spatial autocorrelation analyses showed that temporal and spatial patterns
were tightly linked. Interestingly, despite the fact that the population shows
isolation by time, neighbourhood size and historical dispersal variance (sigma =
63 m) are similar to those detected in pure stands of F. excelsior where
individuals flower rather synchronously and hermaphrodites are not the most
frequent sexual type. Trees flowering at intermediate dates, which comprised the
majority of the population, produced on average more flowers and fruits. We
detected no significant differences in floral parasite infections relative to
reproductive timing, although there was a tendency for late flowering trees to
suffer from more gall attack. We discuss the impact of temporal variation in
fitness traits and their possible role in the maintenance of the hybrid zone.
PMID- 17032265
TI - Worldwide phylogeography of the blacktip shark (Carcharhinus limbatus) inferred
from mitochondrial DNA reveals isolation of western Atlantic populations coupled
with recent Pacific dispersal.
AB - Although many coastal shark species have widespread distributions, the genetic
relatedness of worldwide populations has been examined for few species. The
blacktip shark, (Carcharhinus limbatus), inhabits tropical and subtropical
coastal waters throughout the world. In this study, we examined the genetic
relationships of blacktip shark populations (n = 364 sharks) throughout the
majority of the species' range using the entire mitochondrial control region
(1067-1070 nucleotides). Two geographically distinct maternal lineages (western
Atlantic, Gulf of Mexico, and Caribbean Sea clades, and eastern Atlantic, Indian,
and Pacific Ocean clades) were identified and shallow population structure was
detected throughout their geographic ranges. These findings indicate that a major
population subdivision exists across the Atlantic Ocean, but not the Pacific
Ocean. The historical dispersal of this widespread, coastal species may have been
interrupted by the rise of the Isthmus of Panama. This scenario implies
historical dispersal across the Pacific Ocean (supported by the recovery of the
same common haplotype from the Philippines, Hawaii, and the Gulf of California
reflecting recent/contemporary dispersal abilities) and an oceanic barrier to
recent migration across the Atlantic. Genetic structure within the eastern
Atlantic/Indo-Pacific (Phi(ST) = 0.612, P < 0.001) supports maternal philopatry
throughout this area, expanding previous western Atlantic findings. Eastern
Atlantic/Indo-Pacific C. limbatus control region haplotypes were paraphyletic to
Carcharhinus tilstoni haplotypes in our maximum-parsimony analysis. The greater
divergence of western Atlantic C. limbatus than C. tilstoni from eastern
Atlantic/Indo-Pacific C. limbatus reflects the taxonomic uncertainty of western
Atlantic C. limbatus.
PMID- 17032266
TI - Menage a trois on Macquarie Island: hybridization among three species of fur seal
(Arctocephalus spp.) following historical population extinction.
AB - Human-induced changes to natural systems can cause major disturbances to
fundamental ecological and population processes and result in local extinctions
and secondary contacts between formerly isolated species. Extensive fur seal
harvesting during the nineteenth century on Macquarie Island (subantarctic)
resulted in extinction of the original population. Recolonization by three
species has been slow and complex, characterized by the establishment of breeding
groups of Antarctic and subantarctic fur seals (Arctocephalus gazella and
Arctocephalus tropicalis) and presumed nonbreeding (itinerant) male New Zealand
fur seals (Arctocephalus forsteri). One thousand and seven pups from eight annual
cohorts (1992-2003) were analysed using mitochondrial control region data (RFLP)
and 10 microsatellite loci to estimate species composition and hybridization.
Antarctic fur seals predominated, but hybridization occurred between all three
species (17-30% of all pups). Involvement of New Zealand fur seals was unexpected
as females are absent and males are not observed to hold territories during the
breeding season. The proportion of hybrids in the population has fallen over
time, apparently owing to substantial influxes of pure Antarctic and subantarctic
individuals and non-random mating. Over 50% of New Zealand hybrids and 43% of
Antarctic-subantarctic hybrids were not F(1), which indicates some degree of
hybrid reproductive success, and this may be underestimated: simulations showed
that hybrids become virtually undetectable by the third generation of
backcrossing. While human impacts seem to have driven novel hybridization in this
population, the present 'time slices' analysis suggests some biological
resistance to complete homogenization.
PMID- 17032267
TI - Phylogeography and population structure of thornback rays (Raja clavata L.,
Rajidae).
AB - The phylogeography of thornback rays (Raja clavata) was assessed from European
waters, using five nuclear microsatellite loci and mitochondrial cytochome b
sequences. Strong regional differentiation was found between the Mediterranean
basin, the Azores and the European continental shelf. Allelic and haplotype
diversities were high in Portuguese populations, consistent with the existence of
a refugium along the Iberian Peninsula. Unexpectedly, high diversity was also
found in the English Channel/North Sea area. The lowest genetic diversity was
found in the Black Sea. Populations sampled from the Mediterranean, Adriatic and
Black Seas were characterized by a single mitochondrial haplotype. This haplotype
was also the most ancestral and widespread outside of the Mediterranean basin
except for the Azores. Populations from the Azores were dominated by a second
ancestral haplotype which was shared with British populations. Results from
multidimensional scaling, amova and nested clade analysis indicate that British
waters are a secondary contact zone recolonized from at least two refugia--one
around the Iberian Peninsula and one possibly in the Azores. Links to a potential
refugium known as the Hurd Deep, between Cornwall and Brittany, are discussed.
Finally, a historical demographic analysis indicates that thornback ray
populations started to expand between 580,000 and 362,000 years ago, which
suggests that the Last Glacial Maximum (20,000 years ago) had mainly affected the
distribution of populations rather than population size.
PMID- 17032269
TI - Towards unbiased parentage assignment: combining genetic, behavioural and spatial
data in a Bayesian framework.
AB - Inferring the parentage of a sample of individuals is often a prerequisite for
many types of analysis in molecular ecology, evolutionary biology and
quantitative genetics. In all but a few cases, the method of parentage assignment
is divorced from the methods used to estimate the parameters of primary interest,
such as mate choice or heritability. Here we present a Bayesian approach that
simultaneously estimates the parentage of a sample of individuals and a wide
range of population-level parameters in which we are interested. We show that
joint estimation of parentage and population-level parameters increases the power
of parentage assignment, reduces bias in parameter estimation, and accurately
evaluates uncertainty in both. We illustrate the method by analysing a number of
simulated test data sets, and through a re-analysis of parentage in the
Seychelles warbler, Acrocephalus sechellensis. A combination of behavioural,
spatial and genetic data are used in the analyses and, importantly, the method
does not require strong prior information about the relationship between
nongenetic data and parentage.
PMID- 17032270
TI - Refugia of Potentilla matsumurae (Rosaceae) located at high mountains in the
Japanese archipelago.
AB - Molecular phylogeographic studies have revealed the genetic patterns and glacial
interglacial history of many plant and animal species. To infer the Quaternary
history of alpine plants in the Japanese archipelago, which is poorly known, we
investigated 203 individuals of Potentilla matsumurae and its varieties from 22
populations. We found 11 haplotypes based on approximately 1400 bp of two
intergenetic spacers in chloroplast DNA (trnT-L and rpl20-rps20). The
distribution of these haplotypes was geographically structured, which was
supported by haplotype composition, principal component analysis, and unweighted
pair group method with arithmetic mean (UPGMA), and N(ST) (0.71) was
significantly greater than G(ST) (0.68). In addition to the positive correlation
between genetic and geographic distance (Mantel test, r = 0.497, P < 0.001), an
abrupt genetic change was detected between mountains in central Honshu and the
Tohoku region. This genetic boundary was further supported by analysis of
molecular variance (AMOVA), and high variation (54.0%) was explained by
differences on either side of this boundary. Moreover, haplotypes in central
Honshu were thought to have diverged, based on an outgroup comparison. These
results suggest that mountains in central Honshu served as refugia during the
Quaternary climatic oscillation, although the results could not reveal the
history of most mountains in the Tohoku region and Hokkaido. Nevertheless,
following floristic studies, our results indicate that alpine plants in Japan
experienced a history different from that in Europe; i.e. they retreated into
refugia during warm periods to avoid forest development, rather than glaciers.
PMID- 17032268
TI - Multiple origins of cultivated grapevine (Vitis vinifera L. ssp. sativa) based on
chloroplast DNA polymorphisms.
AB - The domestication of the Eurasian grape (Vitis vinifera ssp. sativa) from its
wild ancestor (Vitis vinifera ssp. sylvestris) has long been claimed to have
occurred in Transcaucasia where its greatest genetic diversity is found and where
very early archaeological evidence, including grape pips and artefacts of a 'wine
culture', have been excavated. Whether from Transcaucasia or the nearby Taurus or
Zagros Mountains, it is hypothesized that this wine culture spread southwards and
eventually westwards around the Mediterranean basin, together with the
transplantation of cultivated grape cuttings. However, the existence of
morphological differentiation between cultivars from eastern and western ends of
the modern distribution of the Eurasian grape suggests the existence of different
genetic contribution from local sylvestris populations or multilocal selection
and domestication of sylvestris genotypes. To tackle this issue, we analysed
chlorotype variation and distribution in 1201 samples of sylvestris and sativa
genotypes from the whole area of the species' distribution and studied their
genetic relationships. The results suggest the existence of at least two
important origins for the cultivated germplasm, one in the Near East and another
in the western Mediterranean region, the latter of which gave rise to many of the
current Western European cultivars. Indeed, over 70% of the Iberian Peninsula
cultivars display chlorotypes that are only compatible with their having derived
from western sylvestris populations.
PMID- 17032271
TI - Genetic diversity and phylogeography of the Apennine yellow-bellied toad Bombina
pachypus, with implications for conservation.
AB - Genetic variation was investigated in 17 populations of the Italian endemic
Apennine yellow-bellied toad using both mitochondrial (598 bp of the cytochrome b
gene) and nuclear (21 allozyme loci) markers. Populations from central Calabria
(southern Italy) showed the highest levels of intrapopulation genetic variation,
whereas samples located north of this region were nearly lacking in variation.
This appears to be a typical pattern of 'southern richness and northern purity',
usually attributed to the prolonged population stability within southern refugia
coupled with the loss of variation during postglacial northward expansion.
However, the overall pattern of genetic variation observed has a strong
geographical component, suggesting two Calabrian plains, Catanzaro and Crati
Sibari, as historical barriers to dispersal separating three population groups.
These findings cannot be explained by the prolonged stability of southern
populations alone, and suggest that the southern richness has been at least in
part shaped by allopatric differentiation within the refugial range, followed by
intermixing of previously differentiated lineages. From a conservation
standpoint, Calabria is the major genetic diversity reservoir for this species,
thus deserving particular conservation efforts. Furthermore, although the low
intrapopulation genetic variation outside Calabria appears to be of clear
historical origin, evidence of a current reduction of gene flow suggests that
human disturbance has also played a part, particularly in the anthropogenic
impacted Volturno river drainage basin.
PMID- 17032272
TI - Hybridization between mtDNA-defined phylogeographic lineages of black ratsnakes
(Pantherophis sp.).
AB - Phylogeographic analyses using mitochondrial DNA (mtDNA) have revealed many
examples of apparently deep historical subdivisions ('phylogroups') within many
vertebrates. It remains unclear whether these phylogroups represent independently
evolving, adaptively differentiated lineages or groups that show little
functional differentiation and, hence, will merge on contact. Here, we use mtDNA
sequence data to evaluate the phylogeographic relationships between two of the
northernmost populations of black ratsnakes (Pantherophis obsoletus complex) in
Ontario, Canada and previously analysed populations in the United States. We then
use population-level analyses to evaluate the level of adaptive divergence
between previously established mtDNA phylogroups. Phylogenetic analyses show that
southern Ontario snakes have mtDNA haplotypes that fall within the Central mtDNA
phylogroup, as designated by Burbrink et al. (2000). In contrast, snakes in
eastern Ontario carry either Central or Eastern-specific haplotypes. Within the
hybrid region, we found highly variable frequencies of mtDNA haplotypes among
isolated sub-populations, no association between variation in cytonuclear (mtDNA)
and nuclear (microsatellite DNA) markers, no difference in survival or
reproductive success among snakes with different mtDNA haplotypes, and no effect
of mate similarity in mtDNA on female clutch size. These results argue that the
Eastern and Central phylogroups have merged in this region, likely due to a lack
of adaptive differentiation between individuals in each lineage. Hence, in these
snakes, phylogeographic structure in mtDNA is more a reflection of historical
isolation rather than adaptive divergence. The observed reticulation between
lineages and lack of evidence for hybrid disgenesis also bears on the
classification of these lineages as distinct species.
PMID- 17032273
TI - Immigration, species radiation and extinction in a highly diverse songbird
lineage: white-eyes on Indian Ocean islands.
AB - Molecular phylogenetic hypotheses of species-rich lineages in regions where
geological history can be reliably inferred may provide insights into the scale
of processes driving diversification. Here we sample all extant or recently
extinct white-eye (Zosterops) taxa of the southwest Indian Ocean, combined with
samples from all principal continental lineages. Results support a high dispersal
capability, with at least two independent continental sources for white-eyes of
the region. An early (within 1.8 million years ago) expansion into the Indian
Ocean may have originated either from Asia or Africa; the three resulting
lineages show a disparate distribution consistent with considerable extinction
following their arrival. Africa is supported as the origin of a later expansion
into the region (within 1.2 million years ago). On two islands, a pair of
Zosterops species derived from independent immigrations into the Indian Ocean co
occur or may have formerly co-occurred, providing strong support for their origin
by double-island colonization rather than within-island (sympatric or
microallopatric) speciation. On Mauritius and La Reunion, phylogenetic placement
of sympatric white-eyes allow us to rule out a scenario in which independent
within-island speciation occurred on both islands; one of the species pairs must
have arisen by double colonization, while the other pair is likely to have arisen
by the same mechanism. Long-distance immigration therefore appears to be
responsible for much of the region's white-eye diversity. Independent
immigrations into the region have resulted in lineages with mutually exclusive
distributions and it seems likely that competition with congeneric species,
rather than arrival frequency, may limit present-day diversity.
PMID- 17032274
TI - Hybridization between subspecies of waterbuck (Kobus ellipsiprymnus) in zones of
overlap with limited introgression.
AB - Two subspecies of waterbuck (Kobus ellipsiprymnus), common (Kobus ellipsiprymnus
ellipsiprymnus) and defassa (Kobus ellipsiprymnus defassa), are recognized based
on differences in rump pattern, coat colour and geographical distribution. These
forms are parapatrically distributed with an area of range overlap in East
Africa, where phenotypically intermediate populations occur. Variation in 478 bp
of the mitochondrial DNA control region and 14 polymorphic microsatellite loci
were used to describe the genetic structure and phylogeographical pattern of the
species, and to assess if the intermediate populations are the results of
hybridization. In total, 186 individuals from 11 localities were analysed. A high
degree of genetic differentiation was found between subspecies, although this was
most evident from the microsatellite data. Hybridization was suggested in the
phenotypically and geographically intermediate Nairobi NP population in Kenya. A
neighbour-joining (NJ) tree based on microsatellite population genetic distances
grouped Nairobi between the common and defassa populations, and a Bayesian
analysis clearly showed introgression. Individuals sampled in Samburu NP, Kenya,
had a common waterbuck phenotype, but introgression was suggested by both
markers. Although a high degree of maternal defassa input was indicated from the
sequence data, the Samburu population grouped with the common waterbuck in the
microsatellite population genetic distance tree, with high support. Analyses of
linkage disequilibrium and maximum-likelihood estimates of genetic drift
suggested that admixture between subspecies is a recent event. The fact that
introgression is limited between subspecies could be caused by chromosomal
differences, hindering gene flow between common and defassa waterbuck.
PMID- 17032275
TI - Temporal recruitment patterns and gene flow in kelp rockfish (Sebastes
atrovirens).
AB - Pelagic dispersal of marine organisms provides abundant opportunity for gene flow
and presumably inhibits population genetic divergence. However, ephemeral, fine
scale, temporal and spatial genetic heterogeneity is frequently observed in
settled propagules of marine species that otherwise exhibit broad-scale genetic
homogeneity. A large variance in reproductive success is one explanation for this
phenomenon. Here, genetic analyses of 16 microsatellite loci are used to examine
temporal patterns of variation in young-of-year kelp rockfish (Sebastes
atrovirens) recruiting to nearshore habitat in Monterey Bay, California, USA.
Population structure of adults from central California is also evaluated to
determine if spatial structure exists and might potentially contribute to
recruitment patterns. Genetic homogeneity was found among 414 young-of-year
sampled throughout the entire 1998 recruitment season. No substantial adult
population structure was found among seven populations spanning 800 km of
coastline that includes the Point Conception marine biogeographic boundary.
Comparison of young-of-year and adult samples revealed no genetic differentiation
and no measurable reduction in genetic variation of offspring, indicating little
variance in reproductive success and no reduction in effective population size
for this year class. Simulation analyses determined that the data set was
sufficiently powerful to detect both slight population structure among adults and
a small reduction in effective number of breeders contributing to this year
class. The findings of high gene flow and low genetic drift have important
implications for fisheries management and conservation efforts.
PMID- 17032276
TI - Postcopulatory inbreeding avoidance by female crickets only revealed by molecular
markers.
AB - Multiple mating is thought to provide an opportunity for females to avoid the
costs of genetic incompatibility by postcopulatory selection of compatible sperm
haplotypes. Few studies have tested the genetic incompatibility hypothesis
directly. Here we experimentally manipulated the compatibility of females with
their mates using the gryllid cricket Teleogryllus oceanicus. We recorded the
hatching success of eggs laid by females mated with two nonsibling males, two
siblings, or one nonsibling male and one sibling. In contrast with two previous
studies on crickets that have adopted this approach, the hatching success of eggs
did not differ between females mated with two full siblings and females mated
with two unrelated males, indicating that embryo viability was not a cost of
inbreeding in this species. We assigned paternity to offspring produced by
females mated to both a sibling and a nonsibling male using microsatellite
markers. As in previous studies of this species, we were unable to detect any
difference in the proportion of offspring sired by the 1st and the 2nd male to
mate with a female when females were unrelated to their mates. However, in our
experimental matings the proportion of offspring sired by the nonsibling male
depended on his sequence position. Paternity was biased toward the nonsibling
male when he mated first. Our data show that molecular analyses of paternity are
essential to detect subtle mechanisms of postcopulatory sexual selection.
PMID- 17032277
TI - Consequences of group fission for the patterns of relatedness among rhesus
macaques.
AB - When mammalian social groups exceed their optimal size, they often tend to split.
In view of the potential evolutionary benefits, it should be more advantageous
for animals to stay with kin, rather than nonkin, during such fission events. In
the present study, the spontaneous fission of two social groups, R and S, of
rhesus macaques living on Cayo Santiago, Puerto Rico, provided the opportunity to
compare the kinship structure of the corresponding parent and daughter groups,
using information on both maternal and paternal relatedness. In both instances,
maternal half-siblings and pairs of animals from the same family were
significantly more prevalent in the fission products than in the parent group.
During the split of group R, significantly more paternal half-siblings stayed in
the remnants of the parent group than joined the seceding group. Our findings are
compatible with previous behavioural studies demonstrating that female primates
bias their social behaviour more to maternal than to paternal kin, but that both
types of half-siblings prefer each other more than unrelated animals. It remains
to be clarified by future research, however, whether the observed co-segregation
of paternal half-sibs in our study reflects active choice or is a by-product of
the group-specific kin structures, prior to fission.
PMID- 17032278
TI - Immune response of nestling warblers varies with extra-pair paternity and
temperature.
AB - Extra-pair mating is widespread in birds, but its adaptive function remains
unclear. It is often suggested that females obtain superior genes for their
offspring as a consequence of extra-pair mating, but the evidence is limited. In
this study, we examined the hypothesis that extra-pair mating provides females
with offspring that have superior immune responses. We found that the T-cell
mediated immune response of extra-pair young was stronger than that of within
pair young in common yellowthroats (Geothlypis trichas). This paternity effect
occurred when we compared all nestlings in the population, as well as in
comparisons of both paternal and maternal half-siblings. Paternal half-siblings
had a stronger immune response when they were produced with extra-pair females
than with the male's social mate, which suggests that the greater immune response
of extra-pair young was caused by nonadditive (compatible) genetic effects.
However, these patterns were only significant in the colder of 2 years. Immune
response was related positively to air temperature and nestlings had a stronger
immune response in the warmer year. We suggest that such environmental variation
could obscure the genetic benefits of extra-pair mating.
PMID- 17032279
TI - Genetic tagging reveals extreme site fidelity in territorial male Antarctic fur
seals Arctocephalus gazella.
AB - Genetic tagging, the identification of individuals using their genotypes,
provides a powerful tool for studying animals that are difficult to observe or
identify using conventional techniques. However, despite being widely adopted by
conservation biologists, the full potential of this approach has yet to be
realized. Here we used genetic recapture data to quantify male site fidelity at a
colony of Antarctic fur seals where an aerial walkway provides unprecedented
access and individual positions are determined daily to 1 m accuracy. Because
males are too large and aggressive to be captured and fitted with conventional
tags, we remotely collected 770 tissue samples over eight consecutive seasons and
used nine-locus microsatellite genotypes to reveal 306 genetic recaptures among
464 unique individuals. Within seasons, males are highly site-faithful, with any
movements that occur tending to take place before the period when females come
into oestrus. Of those males that return to breed over successive seasons, almost
half return to within a body length of where they were before. The discovery of
such extreme site faithfulness has implications for the population structure and
mating system of fur seals and potentially other colonially breeding species.
PMID- 17032280
TI - Diversity of microcystin genotypes among populations of the filamentous
cyanobacteria Planktothrix rubescens and Planktothrix agardhii.
AB - Microcystins (MCs) are toxic heptapeptides that are produced by filamentous
cyanobacteria Planktothrix rubescens and Planktothrix agardhii via nonribosomal
peptide synthesis. MCs share a common structure cyclo (-D-Alanine(1)-L-X(2)- D
erythro-beta-iso-aspartic acid(3)-L-Z(4)-Adda(5)-D-Glutamate(6)- N-methyl
dehydroalanine(7)) where X(2) and Z(2) are variable L-amino acids in positions 2,
4 of the molecule. Part of the mcyB gene (1,451 bp) that is involved in the
activation of the X(2) amino acid during MC synthesis was sequenced in 49 strains
containing different proportions of arginine, homotyrosine, and leucine in
position 2 of the MC molecule. Twenty-five genotypes were found that consisted of
eight genotype groups (A-H, comprising 2-11 strains) and 17 unique genotypes. P.
rubescens and P. agardhii partly consisted of the same mcyB genotypes. The
occurrence of numerous putative recombination events that affected all of the
genotypes can explain the conflict between taxonomy and mcyB genotype
distribution. Genotypes B (homotyrosine and leucine in X(2)) and C (arginine in
X(2)) showed higher nonsynonymous/synonymous (d(N)/d(S)) substitution ratios
implying a relaxation of selective constraints. In contrast, other genotypes
(arginine, leucine, homotyrosine) showed lowest d(N)/d(S) ratios implying
purifying selection. Restriction fragment length polymorphism (RFLP) revealed the
unambiguous identification of mcyB genotypes, which are indicative of variable
X(2) amino acids in eight populations of P. rubescens in the Alps (Austria,
Germany, and Switzerland). The populations were found to differ significantly in
the proportion of specific genotypes and the number of genotypes that occurred
over several years. It is concluded that spatial isolation might favour the
genetic divergence of microcystin synthesis in Planktothrix spp.
PMID- 17032281
TI - Can quantification of faecal occult blood predetermine the need for colonoscopy
in patients at risk for non-syndromic familial colorectal cancer?
AB - BACKGROUND: Patients at risk for non-syndromic (Lynch or polyposis) familial
colorectal neoplasia undergo colonoscopic surveillance at intervals determined by
clinically ascertained protocols. The quantitative immunochemical faecal occult
blood test for human haemoglobin is specific and sensitive for significant
colorectal neoplasia (cancer or advanced adenomatous polyp). AIM: To determine
immunochemical faecal occult blood test efficacy for identifying significant
neoplasia in at-risk patients undergoing elective colonoscopy. METHODS: We
retrospectively identified consecutive at-risk patients who provided three
immunochemical faecal occult blood tests before colonoscopy. Quantitative
haemoglobin analysis was performed by the OC-MICRO automated instrument using the
100 ng Hb/mL threshold to determine positivity. RESULTS: In 252 at-risk patients
undergoing colonoscopy; five had cancer, 14 an advanced adenoma and 46 a non
advanced adenoma. The immunochemical faecal occult blood test was positive in 31
patients (12.3%). Sensitivity, specificity, positive and negative predictive
values for cancer were: 100%, 90%, 16% and 100%, and for all significant
neoplasia: 74%, 93%, 45% and 98%. With 88% fewer colonoscopies, all colorectal
cancers and 74% of all significant neoplasia would have been identified by this
one-time immunochemical faecal occult blood test screening. CONCLUSIONS: A
sensitive, non-invasive, interval screening test might be useful to predetermine
the need for colonoscopy in this at-risk population and minimize unnecessary
examinations. This favourable retrospective evaluation will be extended to a
prospective study.
PMID- 17032282
TI - Third-line rescue therapy with levofloxacin is more effective than rifabutin
rescue regimen after two Helicobacter pylori treatment failures.
AB - BACKGROUND: In patients with a first eradication failure, a second (rescue)
therapy still fails in > 20% of cases. AIM: To compare rifabutin and levofloxacin
rescue regimens in patients with two consecutive Helicobacter pylori eradication
failures. METHODS: Patients, in whom first treatment with omeprazole
clarithromycin-amoxicillin and a second trial with omeprazole-bismuth
tetracycline-metronidazole (or ranitidine bismuth citrate with these antibiotics)
had failed, received 10 days of treatment with either rifabutin (150 mg b.d.) or
levofloxacin (500 mg b.d.), plus amoxicillin (1 g b.d.) and omeprazole (20 mg
b.d.). Cure rates were evaluated by the (13)C-urea breath test. RESULTS: Twenty
patients received rifabutin, and 20 levofloxacin. All the patients returned for
follow-up. Compliance in the rifabutin group was 100%. Four patients in the
levofloxacin group did not take the medication correctly (in two cases due to
adverse effects: myalgia and rash). Side effects in the rifabutin and
levofloxacin groups were reported in 60% and 50% of the cases, respectively. Five
patients (25%) treated with rifabutin presented with leucopenia, and six (30%)
treated with levofloxacin presented with myalgias. Per-protocol cure rates were
45% (95% confidence interval, 26-66%) in the rifabutin group, and 81% (57-93%) in
the levofloxacin group (P < 0.05). Intention-to-treat cure rates were, 45% (26
66%) and 85% (64-95%), respectively (P < 0.01). CONCLUSIONS: After two previous
H. pylori eradication failures, a 10-day triple levofloxacin-based rescue regimen
is more effective than the same regimen with rifabutin.
PMID- 17032283
TI - Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter
pylori treatment in children: a randomized placebo controlled trial.
AB - BACKGROUND: Helicobacter pylori eradication fails in about 25-30% of children,
particularly because of the occurrence of resistance to antibiotics and side
effects. AIM: To determine whether adding the Lactobacillus reuteri to an anti-H.
pylori regimen could help to prevent or minimize the gastrointestinal side
effects burden in children. METHODS: Forty H. pylori-positive children (21 males;
median age: 12.3 years) were consecutively treated with 10-day sequential therapy
[omeprazole + amoxycillin for 5 days, and omeprazole + clarithromycin +
tinidazole for other 5 days] and blindly randomized to receive either L. reuteri
ATCC 55730 (10(8) CFU) or placebo. All children completed the Gastrointestinal
Symptom Rating Scale (GSRS) at entry, during and after treatment. H. pylori
status was assessed after 8 weeks by (13)C-urea breath test. RESULTS: Overall, in
all probiotic supplemented children when compared with those receiving placebo
there was a significant reduction of GSRS score during eradication therapy (4.1
+/- 2 vs. 6.2 +/- 3; P < 0.01) and at the end of follow-up (3.2 +/- 2 vs. 5.8 +/-
3.4; P < 0.009). Overall, children receiving L. reuteri report less symptoms than
those receiving placebo. CONCLUSION: L. reuteri is capable of reducing frequency
and intensity of antibiotic-associated side-effects during eradication therapy
for H. pylori.
PMID- 17032284
TI - Corpus-predominant gastritis as a risk factor for false-negative 13C-urea breath
test results.
AB - BACKGROUND: Urea breath test sensitivity seems affected by increased intragastric
acidity during therapy with antisecretory drugs. Intragastric pH is increased in
patients with corpus gastritis with/without atrophy. AIM: To test the hypothesis
that urea breath test results may also be affected by this gastritis phenotype.
METHODS: 123 untreated patients underwent gastroscopy plus biopsies and
intragastric pH measurement. The study included 82 endoscopically proven
Helicobacter pylori-positive patients who were offered urea breath test with an
acidic meal. Histological findings, urea breath test results and intragastric pH
were compared in 66 of the subjects. RESULTS: 21 of 66 (31.8%) patients had a
false-negative urea breath test. In these patients corpus-predominant gastritis
(85.7% vs. 37.7%; P = 0.0004) and fundic atrophy (66.6% vs. 17.7%; P = 0.0001)
were more frequent than in patients with true-positive urea breath test.
Intragastric pH was higher in false-negative patients (mean 6.3 vs. 4.4; P =
0.001). In a multivariate analysis, the only risk factor for a false-negative
urea breath test was the presence of corpus-predominant gastritis (OR = 5.6; 95%
CI: 1.1-27). There was a negative correlation between the intragastric pH and the
delta over baseline values (r = -0.378; P = 0.0023). CONCLUSIONS: Our results
support the hypothesis that the pattern of gastritis can affect the sensitivity
of urea breath test, and suggest that patients with corpus-predominant gastritis
have a high risk of false-negative urea breath test results.
PMID- 17032285
TI - A comparative study of intragastric acidity during post-breakfast and pre-dinner
administration of low-dose proton pump inhibitors: a randomized three-way
crossover study.
AB - BACKGROUND: The absorption and bioavailability of proton pump inhibitors is
influenced by food intake. Proton pump inhibitors bind to the parietal cell
active proton pump, which is maximally stimulated after dinner: usually the
largest meal of the day. However, it has not been fully clarified whether the
efficacy of proton pump inhibitors differs between post-breakfast and pre-dinner
dosing. AIM: To perform a pH-monitoring study to clarify this issue for two low
dose proton pump inhibitors. SUBJECTS AND METHODS: The subjects were 20 healthy
male volunteers (seven Helicobacter pylori-positive and 13 H. pylori-negative),
who were divided into two groups of 10 and administered 15 mg lansoprazole or 10
mg rabeprazole, respectively. All subjects underwent ambulatory intragastric 24-h
pH- monitoring under three conditions allocated randomly: (i) without medication,
(ii) seventh day of post-breakfast administration and (iii) eighth day of pre
dinner administration of each drug. RESULTS: There was no significant difference
in the percentage time during which pH > or =4.0 in the 24-h period between post
breakfast and pre-dinner administration of both drugs (56.6% vs. 55.8%; P =
0.557), although intragastric acidity during administration of both drugs was
significantly lower than that without medication. CONCLUSIONS: The timing of drug
administration does not significantly influence the efficacy of low-dose proton
pump inhibitors.
PMID- 17032286
TI - Outcome of peptic ulcer bleeding among users of traditional non-steroidal anti
inflammatory drugs and selective cyclo-oxygenase-2 inhibitors.
AB - BACKGROUND: Few data exist on the impact of non-steroidal anti-inflammatory drug
use on peptic ulcer outcome. AIM: To examine the 30-day mortality from peptic
ulcer bleeding associated with the use of traditional non-steroidal anti
inflammatory drugs and newer selective cyclo-oxygenase-2 inhibitors. METHODS:
Cohort study of patients with a first hospitalization for peptic ulcer bleeding
in three Danish counties between 1991 and 2003. Data on pre-admission non
steroidal anti-inflammatory drug use, use of other ulcer-related drugs and
comorbidities were obtained from population-based registries. Follow-up data on
mortality were obtained from the Danish Civil Registry System. RESULTS: Of 7,232
patients hospitalized for peptic ulcer bleeding, 28% were current non-steroidal
anti-inflammatory drug users. Thirty-day mortality was 11% overall, and 13% among
current non-steroidal anti-inflammatory drug users. Compared with never-use, the
adjusted 30-day mortality rate ratios were 1.4 (95% CI: 1.1-1.9) for current use
of non-steroidal anti-inflammatory drugs alone and 1.3 (95% CI: 1.0-1.7) for
current use combined with other ulcer-related drugs. For users of celecoxib,
alone and in combination, adjusted mortality rate ratios were 1.4 (95% CI: 0.5
3.9) and 2.0 (95% CI: 1.2-3.5), and for users of rofecoxib, 1.2 (95% CI: 0.4-3.9)
and 0.9 (95% CI: 0.5-1.6). CONCLUSION: Among patients hospitalized with peptic
ulcer bleeding, use of non-steroidal anti-inflammatory drugs, including some
newer cyclo-oxygenase-2 inhibitors, is associated with increased short-term
mortality.
PMID- 17032288
TI - Polymorphisms in the angiotensin converting enzyme gene and growth in the first
year of life.
AB - Abnormal patterns of fetal and infant growth have been associated with an
increased risk of cardiovascular disease in adulthood. Catch-up growth during the
first year of life has been associated with a higher prevalence of type 2
diabetes mellitus, whereas a lack of catch-up growth tracks with a risk of
hypertension. The role of genetic factors influencing both growth and blood
pressure have not been explored. We genotyped cord blood samples from 530
singleton, Caucasian, uncomplicated pregnancies, drawn from a larger cohort of
1650 pregnancies, and related polymorphism in the angiotensin converting enzyme
(ACE) gene (alleles insertion (I) or deletion (D)) with measures of size at birth
and at age of 1 year. ACE genotype did not significantly influence size at birth,
although there was a greater proportion of individuals with the D/D genotype born
with a birth weight less than the 10th centile (P=0.004). The ACE I/I genotype
was significantly associated with higher weight (p=0.001), body mass index
(p=0.001) and mid arm circumference (p=0.001) at 1 year of age compared to the
ACE D/D and I/D genotypes. Individuals with the I/I genotype displayed catch-up
(gain from birth size of >or=0.6 Standard Deviation Score) in weight (p=0.04),
body mass index (p=0.03) and mid arm circumference (p=0.03) compared to the D/D
group, the majority of which showed no change or catch-down. The I/D genotype was
distributed equally across the catch up/catch down/no change categories. The
effect was more marked in males, but ACE genotype and sex of the infant
contributed independently to mid arm circumference measurements and there was no
interaction between the two. There was no effect of maternal or paternal ACE
genotype on birth size. In a multiple linear regression model ACE genotype,
socioeconomic status and sex of the infant explained 10.9% of the variance in
body mass index SDS at 1 year of age. We conclude that the ACE I/I genotype is
associated with a higher weight and body mass index SDS at 1 year of age, along
with catch-up in terms of these measures from birth to 1 year. The D/D genotype
is associated with a greater proportion of babies, born at term, that at small
for gestational age. These results suggest that due consideration should be given
to the underlying genotype of an individual when evaluating the association of
early human growth with the development of risk factors for cardiovascular
disease. The observation of independent effects of genotype, sex of the
individual and socioeconomic status on postnatal growth suggests the need to
develop methodologies for the integration of genetic and environmental factors in
causality modelling.
PMID- 17032287
TI - Mixed-effects logistic approach for association following linkage scan for
complex disorders.
AB - An association study to identify possible causal single nucleotide polymorphisms
following linkage scanning is a popular approach for the genetic dissection of
complex disorders. However, in association studies cases and controls are assumed
to be independent, i.e., genetically unrelated. Choosing a single affected
individual per family is statistically inefficient and leads to a loss of power.
On the other hand, because of the relatedness of family members, using affected
family members and unrelated normal controls directly leads to false-positive
results in association studies. In this paper we propose a new approach using
mixed-model logistic regression, in which associations are performed using family
members and unrelated controls. Thus, the important genetic information can be
obtained from family members while retaining high statistical power. To examine
the properties of this new approach we developed an efficient algorithm, to
simulate environmental risk factors and the genotypes at both the disease locus
and a marker locus with and without linkage disequilibrium (LD) in families.
Extensive simulation studies showed that our approach can effectively control the
type-I error probability. Our approach is better than family-based designs such
as TDT, because it allows the use of unrelated cases and controls and uses all of
the affected members for whom DNA samples are possibly already available. Our
approach also allows the inclusion of covariates such as age and smoking status.
Power analysis showed that our method has higher statistical power than recent
likelihood ratio-based methods when environmental factors contribute to disease
susceptibility, which is true for most complex human disorders. Our method can be
further extended to accommodate more complex pedigree structures.
PMID- 17032289
TI - Computing power in case-control association studies through the use of quadratic
approximations: application to meta-statistics.
AB - In the framework of case-control studies many different test statistics are
available to measure the association of a marker with a given disease.
Nevertheless, choosing one particular statistic can lead to very different
conclusions. In the absence of a consensus for this choice, a tempting option is
to evaluate the power of these different statistics prior to make any decision.
We review the available methods dedicated to power computation and assess their
respective reliability in treating a wide range of tests on a wide range of
alternative models. Considering Monte-Carlo, non-central chi-square and Delta
Method estimates, we evaluate empirical, asymptotic and numerical approaches.
Additionally we introduce the use of the Delta-Method, extended to order 2,
intended to provide better results than the traditional order-1 Delta-Method.
Supplementary data can be found at: http://stat.genopole.cnrs.fr/software/dm2.
PMID- 17032290
TI - Training in rural practice: time for integration?
PMID- 17032291
TI - Training doctors in general practices: a review of the literature.
AB - OBJECTIVE: This study was undertaken to assess the evidence of whether new forms
of medical training, where substantial training takes place in general practice,
will be acceptable to GPs. In particular, we asked the questions: Are GPs willing
to act as trainers and supervisors in their practices? Do GPs have the
appropriate skills to be trainers? Do practices have the infrastructure and
resources to support placements? And, are patients happy to be seen by medical
students and General Practice Registrars? DESIGN: Key Australian and
international databases, key Australian journals and key Australian websites were
searched for literature on general practice-based training of medical students
and General Practice Registrars. RESULTS: In the international and Australian
literature, we found that many GPs consider training medical students and General
Practice Registrars to be intrinsically satisfying. They vary in their skills,
and most medical schools have made significant investments in training and
support activities. Many practices do not have the necessary infrastructure, and
investments need to be made if extended placements are to be successful. Many
patients are happy to be seen by students and Registrars, but careful thought
needs to be given to implementing appropriate models so that students have good
learning opportunities, patients are not disadvantaged and general practices can
operate efficiently. CONCLUSION: The success of this new model of clinical
placements is dependent on medical schools having a detailed understanding of the
needs and expectations of GPs.
PMID- 17032292
TI - Housing and health in Indigenous communities: key issues for housing and health
improvement in remote Aboriginal and Torres Strait Islander communities.
AB - Indigenous people living in remote communities face some particular difficulties
with regard to housing and its impact on their health. This paper reviews the
contemporary international understanding of the relationship between housing and
health, the history of settlement and housing conditions in remote Aboriginal and
Torres Strait Islander communities, and some of the recent initiatives to improve
housing in these communities.
PMID- 17032293
TI - Partnerships in specialty care: exploring rural haemophilia provider resource
needs.
AB - OBJECTIVE: The purpose of this study was to determine whether rural providers
have adequate preparation for safe and effective haemophilia care. DESIGN: This
qualitative study proceeded in two phases: focus group (phase I) and telephone
(phase II) interviews. SETTING: Five Canadian rural hospitals served by one urban
haemophilia treatment centre and providing service to at least one haemophilia
family. PARTICIPANTS: Phase I: focus groups of rural health professionals (site
1: n = 5; site 2: n = 6), including nursing, medicine and lab technology. Phase
II: telephone interviews with nine participants from nursing, medicine, lab
technology, social work and physiotherapy across three sites. MAIN OUTCOME
MEASURES: Qualitative content analysis yielded categorical themes for specialty
care resource requirements in a rural context. RESULTS: Resource needs reflected
five main categories: communication network, subjective knowledge, team roles,
objective knowledge and partnerships (C-STOP). CONCLUSIONS: The five C-STOP
categories require resources and alignment of urban specialist, rural provider
and family expertise. Specialty clinic efforts promoting self-care are incomplete
without matched resources for rural providers.
PMID- 17032294
TI - Motorcycle deployment and rider characteristics on Victorian farms.
AB - OBJECTIVE: To describe the motorcycle fleet and rider characteristics on
Victorian farms. DESIGN: Cross-sectional postal survey. SETTING: Victorian
agricultural industries. PARTICIPANTS: A total of 1382 randomly selected farmers
in 2001. MAIN OUTCOME MEASURES: Farm motorcycle characteristics, use and
maintenance schedule; motorcycle rider characteristics, respondent demographics
and property characteristics. RESULTS: A total of 70% of farms had motorcycles,
with an average of 1.7 per property. A total of 49% were four-wheel, and 44% were
two-wheel. The average engine size and age were 255 cc and 8.8 years,
respectively. The milk cattle sector owned the largest share of the motorcycle
fleet and cereal/grain farms the smallest share. Four-wheel motorcycles were
often used across the entire spectrum of agricultural tasks. Two-wheel motorcycle
use was concentrated more on mustering and transport. A total of 61% of farms
performed motorcycle maintenance every 1-6 months. Fifteen per cent of riders
were under 15 years of age, and the majority (71%) rode four-wheel motorcycles. A
total of 29% of all riders had received some form of motorcycle training.
CONCLUSIONS: This study provides useful information on state-level patterns of
farm motorcycle use, as well as the key safety behaviours of rider training and
motorcycle maintenance. This information might serve as baseline data for future
monitoring and surveillance, and might assist with planning of prevention
programs.
PMID- 17032295
TI - Impact of support initiatives on retaining rural general practitioners.
AB - OBJECTIVE: This study aimed to evaluate the impact of the Dr DOC program, a rural
doctor workforce support program, which consists of social and psychological
support and practical interventions, on the well-being and retention of rural
GPs. DESIGN: Rural GPs were assessed on different aspects of well-being and their
intentions to leave rural general practice, and these were compared with similar
data collected two years prior. SETTING: Rural general practices in South
Australia. PARTICIPANTS: Two hundred and twenty-one rural GPs (55% of South
Australian rural GP workforce). MAIN OUTCOME MEASURES: GPs completed a
questionnaire assessing their levels of support, intention to leave rural
practice, use of the dr doc program, and psychological health. RESULTS:
Improvements were found in the support networks and in the physical and emotional
health of rural GPs from time 1 to time 2. There was also a reduction in the
number of GPs wanting to leave rural general practice in the short to medium term
(from 30% to 25%). CONCLUSIONS: The initial study in this series suggested that
improving psychological well-being might influence rural GPs' intentions to leave
rural practice. The current study confirms these suggestions by demonstrating
that programs targeted at psychological and physical well-being do indeed impact
on rural GPs' intentions to leave. The results of this study highlight the role
of psychological well-being in retaining rural GPs and emphasise the value of
developing psychologically based programs to not only boost the physical and
mental health of GPs, but also to reduce departure from rural areas.
PMID- 17032296
TI - Orientation for general practice in remote Aboriginal communities: a program for
registrars in the Northern Territory.
AB - BACKGROUND: Remote general practice can be a highly rewarding career, but poses
many personal and professional challenges. It is characterised by significant
geographical, professional and social isolation and a requirement for
practitioners with public health, emergency and extended clinical skills. The
remote practitioner faces further challenges in the remote Aboriginal community
setting, including language and cultural barriers. OBJECTIVES: This paper
discusses the specific components of a remote Aboriginal community general
practice registrar orientation program in the Northern Territory, and their
particular importance and relevance to remote training and practice in this
context. DISCUSSION: Northern Territory General Practice Education, the regional
general practice training provider in the Northern Territory, has developed a
model for a comprehensive orientation program for general practice registrars
planning to work in remote Aboriginal community locations. This comprises a
number of core components, including communication and cultural safety training;
clinical and procedural skill development; population health; self-care and
personal/professional role delineation; and organisational issues. We believe it
is a program that is applicable to other disciplines undertaking work in remote
Aboriginal communities.
PMID- 17032297
TI - Small-area estimates of general practice workforce shortage in rural and remote
Western Australia.
AB - OBJECTIVE: To trial a measure of rural and remote GP access for small areas.
DESIGN: A cross-sectional study using geographical information systems software
to calculate GP to population rates with a floating catchment of 100 km radius
around census collection districts (CCDs). SETTING: Non-metropolitan Western
Australia. PARTICIPANTS: The locations and full-time equivalents of GPs and other
primary-care doctors were identified through a GP workforce survey. MAIN OUTCOME
MEASURES: GP to population ratios for each CCD were classified as being above or
below a benchmark of adequate GP access. CCDs with no GP sessions reported within
100 km were identified separately. These categories were investigated by
divisions of general practice and by indigenous status, age and employment
characteristics of the population. RESULTS: Small-area estimates detected greater
variation in access than depicted by conventional methods. Sixty-four per cent of
the non-metropolitan population live in CCDs with adequate GP access. Forty-five
per cent of indigenous people and 52% of people working in rural industries live
in CCDs with access below the benchmark. CONCLUSIONS: The floating catchment
method is a powerful tool to identify small areas of inadequate service. It can
be applied to measure access to other professionals, medical equipment or
facilities.
PMID- 17032298
TI - Factors affecting the recruitment and retention of pharmacists to practice sites
in rural and remote areas of New South Wales: a qualitative study.
AB - OBJECTIVE: To explore factors affecting recruitment and retention of pharmacists
in rural/remote areas of New South Wales (NSW). DESIGN: Qualitative
semistructured in-depth interviews. SETTING: Primary care--rural/remote community
pharmacies. PARTICIPANTS: Purposive sample of 12 community pharmacists. MAIN
OUTCOME MEASURES: Factors affecting recruitment and retention of pharmacists in
rural/remote areas of NSW. RESULTS: Respondents reported a variety of personal
and professional reasons for taking up rural practice, including previous rural
experience and a preference for working in rural over metropolitan areas. The
main factor affecting retention in rural areas was the high level of professional
satisfaction and interprofessional rapport. Perceived reasons for the current
under-supply of pharmacists to rural/remote areas of NSW included changing
demographics of the pharmacy undergraduate degree programs and pharmacy
workforce, and negative perceptions of rural pharmacy practice and rural
lifestyle. CONCLUSIONS: This study identified factors believed to affect
recruitment and retention of pharmacists in rural/remote areas. There appears to
be considerable overlap between the factors, with different weightings of
importance for different individuals. The lack of consensus for a proposed method
of resolving this problem highlights its complexity and the need for further
studies in this area.
PMID- 17032299
TI - Wagga Wagga specialist outreach palliative medicine service: a report on the
first 12 months of service.
AB - OBJECTIVE: This paper reports on and discusses the development of a visiting
palliative medicine specialist outreach service for Wagga Wagga New South Wales,
Australia, and presents initial data and three case vignettes for reflection. The
visiting doctor was flown from Sydney each fortnight for a day and integrated
with the local nursing based palliative care team. METHODS: Demographic data was
collected over the initial 12 months of service, which included the location of
the consult (hospital, home, nursing home), whom the consult was from
(specialist, GP), age of the patient, location of death, type of cancer, as well
as the complexity of consultation from the perspective of one of the authors.
RESULTS: The majority of referrals were for advice on cancer pain control (62.3%)
and other symptoms (26.7%) confirming the expectation. Those patients referred
were considered appropriate, with over 75% having a palliative care issue that
was considered appropriate for direct patient contact by the specialist in
palliative medicine. CONCLUSIONS: The provision of a visiting palliative medicine
specialist to rural areas has been developed over the last few years in New South
Wales and the reporting of the success of this particular service aims to provide
evidence for the need and the development of further services, as it is expected
that this service would continue but with an increasing number of referrals as
the service became increasingly known.
PMID- 17032300
TI - Preparing professionals from a wide range of disciplines for life and work in
rural and small communities.
AB - A new inter-professional subject has been offered at a Canadian university, which
examines issues related to professionals' integrating into rural practice;
understanding the history and geography of rural communities and important issues
affecting life in rural settings.
PMID- 17032301
TI - Rural women's referral journeys after myocardial infarction.
PMID- 17032302
TI - Career preferences of new medical students at four Australian universities: rural
family medicine versus the rest.
PMID- 17032303
TI - Limited wrist arthrodesis.
PMID- 17032304
TI - Walking the void: being a rural PhD candidate.
PMID- 17032305
TI - Managing staff turnover: orientation packs.
PMID- 17032308
TI - SARRAH: Looming crisis in undergraduate allied health professional clinical
placements.
PMID- 17032310
TI - Anti-tumor effect in an in vivo model by human-derived pancreatic RNase with
basic fibroblast growth factor insertional fusion protein through antiangiogenic
properties.
AB - It is thought that the export of angiogenic fibroblast growth factors (FGF) from
tumors may be involved in the onset of tumor angiogenesis. To create a new active
targeting drug that inhibits the tumor angiogenic process without toxicities to
normal cells, human basic FGF (h-bFGF) was inserted genetically into the Gly89
position of cross-linked RNase1 (the ribonuclease inhibitor protein [RI] binding
site of cross-linked human pancreatic RNase) to prevent stereospecific binding to
RI. The resultant insertional-fusion protein (CL-RFN89) was active both as h-bFGF
and as RNase1. Furthermore, it acquired an additional ability of evading RI
through steric blockade of RI binding caused by the fused h-bFGF domain. In the
present study, the effect of the resultant protein, CL-RFN89, on the antitumor
response though its antiangiogenic properties was investigated in an in vivo
model. Continuous systemic treatment with CL-RFN89 significantly inhibited the
growth of human A431 squamous cell carcinomas in vivo. Seven days of treatment
with CL-RFN89 resulted in a 58.2% inhibition of tumor growth compared with
control mice (P < 0.0001). Furthermore, immunohistochemistry using a rat
antimouse CD31 antibody showed that treatment with CL-RFN89 reduced tumor
vascularization. These findings identify CL-RFN89 as a potent systemic inhibitor
of tumor growth as a result of its antiangiogenic properties. This protein
appears to be a new systemic antitumor agent.
PMID- 17032311
TI - Inhibitory effect of c-Met mutants on the formation of branching tubules by a
porcine aortic endothelial cell line.
AB - The association of hepatocyte growth factor (HGF) with its high-affinity receptor
(c-Met) has been shown to induce mitogenesis, motogenesis and morphogenesis in a
variety of cell types. Various point mutations in c-Met have been identified in
hereditary and sporadic papillary renal carcinomas as well as in other
carcinomas. In the present study, we examined the effects of c-Met point
mutations on the morphology of a porcine aortic endothelial (PAE) cell line. When
cultured in three-dimensional collagen gel, PAE cells formed branching tubule
structures, and HGF treatment caused breakdown of the structures and induced a
scattered morphology. The exogenous expression of c-Met point mutants inhibited
the formation of tubules. HGF treatment induced the formation of tubules by PAE
cells expressing some c-Met mutants, but it induced the scattering of PAE cells
expressing other c-Met mutants. The presence of a low concentration of a mitogen
activated protein kinase/extracellular signal-regulated kinase kinase (MEK)
inhibitor cancelled the inhibitory effect of the c-Met point mutations on the
formation of tubules. These results suggest that c-Met point mutations affect the
extracellular signal-regulated kinase (ERK) signaling required for the formation
of tubules by PAE cells, and HGF binding changes the conformation of c-Met
mutants, leading to the different signals required for formation of tubules and
cell scattering.
PMID- 17032312
TI - Genetic instability on chromosome 17 in the epithelium of non-polypoid colorectal
carcinomas compared to polypoid lesions.
AB - Early colorectal carcinomas (submucosal invasive adenocarcinomas) can be
classified into polypoid growth carcinoma (PG-Ca) and non-polypoid growth
carcinoma (NPG-Ca) types, the latter transforming more rapidly to advanced
carcinoma. Previously, we indicated that stromal genetic instability might
contribute to tumorigenesis of both sporadic and ulcerative colitis-associated
colorectal adenocarcinomas. In the present study, we analyzed genetic instability
of both epithelial and surrounding stromal components in PG-Ca and NPG-Ca. In 99
colorectal submucosal invasive adenocarcinomas, epithelial and stromal genetic
instability was analyzed with National Cancer Institute standard microsatellite
markers, chromosome 17 (Chr.17) markers and tumor suppressor gene-related
markers, using a combination of the laser-captured microdissection and GeneScan
approaches. Immunohistochemical analysis was carried out for hMLH1, hMSH2, MGMT
and p53. In addition, we investigated methylation of the hMLH1 and MGMT
promoters. The frequencies of epithelial microsatellite instability (MSI) with
Chr.17 markers were significantly higher in NPG-Ca (33.3%) compared to PG-Ca
(10.4%), particularly with D17S579 and D17S796. For loss of heterozygosity, only
D17S786 showed a significant difference. The frequencies of stromal MSI with all
markers were 31.7% and 25.9% in NPG-Ca and PG-Ca, respectively, but D17S579 and
TP53 showed higher MSI in NPG-Ca than PG-Ca. Immunohistochemically, p53 protein
expression in PG-Ca was significantly higher in loss of heterozygosity-positive
cases with altered Chr.17 markers overall, especially the D17S796 marker,
compared to cases without genetic instability. These results suggest that
epithelial and stromal MSI of Chr.17 markers contributes more to carcinogenesis
in NPG-Ca, whereas stromal genetic instability might be necessary for the
development of both types of colorectal carcinoma.
PMID- 17032313
TI - Therapeutic targeting of the endothelin a receptor in human nasopharyngeal
carcinoma.
AB - The endothelin A receptor (ET(A)R) autocrine pathway is overexpressed in many
malignancies, including nasopharyngeal carcinoma (NPC). In this tumor, ET(A)R
expression is an independent determinant of survival and a robust independent
predictor of distant metastasis. To evaluate whether ET(A)R represents a new
target in NPC treatment, we tested the therapeutic role of ET(A)R in NPC. Cell
proliferation was inhibited by the ET(A)R-selective antagonist ABT-627 in two
ET(A)R-positive NPC cells in a dose-dependent manner. Proliferation of ET(A)R
negative NPC cells was not decreased. ET(A)R blockade also resulted in
sensitization to cisplatin and 5-fluorouracil-induced apoptosis. In nude mice,
ABT-627 inhibited the growth of NPC cell xenografts. Combined treatment of ABT
627 with the cytotoxic drug cisplatin or 5-fluorouracil produced additive
antitumor effects. The antitumor activity of ABT-627 was demonstrated finally on
an experimental lung metastasis by a reduction in the number of tumors. These
results support the rationale of combining ABT-627 with current standard
chemotherapy to further improve the therapeutic ratio in the treatment of NPC.
PMID- 17032315
TI - Er:YAG laser resurfacing for inoperable medium-sized facial congenital
melanocytic naevi in children.
AB - Congenital melanocytic naevi (CMN) can cause significant psychosocial morbidity,
especially if they are in visually exposed areas. The preferred treatment is
surgical excision, though not all lesions are amenable to this because anatomical
location may preclude aesthetic and functional reconstruction. Three children
with inoperable facial CMN were treated with Er:YAG resurfacing under general
anaesthetic. Two children were Fitzpatrick skin type II, and one child was skin
type VI. Treatment was performed at 4-9-monthly intervals. The procedure achieved
significant lightening and thinning in all three cases, without scarring or
dyspigmentation. One child developed herpes simplex infection in the treated area
on one occasion, which was managed with oral aciclovir, and did not lead to
scarring or preclude further treatment. We conclude that Er:YAG laser resurfacing
is effective for CMN, even in darker skin types. The incidence of side-effects is
low, although repeated treatment is necessary.
PMID- 17032316
TI - Effects of oral isotretinoin therapy on peripheral nerve functions: a preliminary
study.
AB - Accumulating evidence over the past decade indicates that synthetic retinoids may
be capable of affecting both growth and differentiation of nervous tissue. Our
aim was to substantiate possible side-effects of oral isotretinoin therapy on
peripheral nerve functions, both neurologically and neurophysiologically. We
performed neurological examination and electroneuromyographic studies on 18
patients with various skin diseases before, at the third month, and at the end of
isotretinoin treatment. Abnormal neurophysiological findings in this study point
towards a typical distal, length-dependent and predominantly sensory
polyneuropathy. Clinicians should be aware of possible neurological sensorial
symptoms during isotretinoin therapy. In our opinion, electroneuromyographic
investigation should be performed on all patients reporting symptoms (e.g.
paresthesia, numbness, sensory loss) before and during oral isotretinoin
treatment. The precise clinical significance of the isotretinoin-induced
neurophysiological alterations reported here remains to be determined in further
studies.
PMID- 17032317
TI - Transanal endoscopic microsurgery: the preferred technique in a small but
important group of rectal neoplasms.
PMID- 17032318
TI - Surgery for local recurrence of rectal cancer.
AB - OBJECTIVE: Despite improvement in management of primary rectal cancer, 2.6-32% of
patients develop local recurrence. A proportion of these patients can be amenable
to salvage surgery. The present article reviews the evidence for and against the
surgical management for local recurrence of rectal cancer, the role of adjuvant
and intraoperative radiotherapy (IORT), and evaluates short and long-term
outcomes. METHOD: A literature search was performed using Medline, Embase, Ovid
and Cochrane database for studies between 1980 and 2005 assessing surgical
management of local recurrence of rectal cancer and the evidence was critically
evaluated. RESULTS: Nearly 50% of rectal cancer recurrences are local and are
therefore potentially amenable to curative resection. Preoperative imaging is
important for appropriate selection of patients for surgery and preoperative
adjuvant therapy is essential. Five-year survival following resection ranges from
18% to 58% with 5-year survival following complete resection of over 35% though
morbidity ranges from 21% to 82%. Neoadjuvant radiotherapy is beneficial and IORT
may have a contributory role in treatment. Aggressive surgical treatment
favourably affects quality of life and is cost effective. Surgery for local
recurrence can result in significant long-term survival with acceptable morbidity
and improved quality of life in appropriately selected patients. Assessment in a
specialist centre familiar with these techniques is essential.
PMID- 17032319
TI - Life-threatening sepsis following treatment for haemorrhoids: a systematic
review.
AB - INTRODUCTION: Haemorrhoids are a common complaint with estimates suggesting a
prevalence of 4% of the adult population. Treatments such as rubber band ligation
(RBL), sclerotherapy and excisional surgery have been in use for many years, and
recently stapled haemorrhoidopexy, or procedure for prolapsing haemorrhoids (PPH)
has gained acceptance. However, there have been consistent reports of severe
sepsis, including a number of deaths. The purpose of this review was to assess
the scale of the problem, and identify any predisposing factors, common
presenting features, and treatment options in those who suffer these
complications. RESULTS: Twenty-nine papers were identified, reporting 38
patients. Of these, 17 had undergone RBL, three had sclerotherapy, one had
cryotherapy, 10 had excisional surgery and seven had PPH. Ten died as a result of
their sepsis. The cases included 16 with perineal sepsis, seven with
retroperitoneal gas and oedema, and six with liver abscesses. Common presenting
features were urinary difficulties, fever, severe pain, septic shock and
leucocytosis. Most were managed by means of surgery, although a minority survived
having received conservative therapy. With the exception of two patients (one of
whom was human immunodeficiency virus positive and the other had a drug-induced
agranulocytosis) all were well prior to surgery. CONCLUSIONS: Although extremely
uncommon, severe sepsis does occur post-treatment for haemorrhoids and all
surgeons who treat such patients should be aware of the potential complications
and alert to their presenting features. Early presentation without evidence of
tissue necrosis may be managed conservatively, although most cases are managed by
means of surgery.
PMID- 17032320
TI - Short course preoperative radiotherapy is the single most important risk factor
for perineal wound complications after abdominoperineal excision of the rectum.
AB - AIM: To determine factors associated with perineal wound complications following
abdominoperineal excision of the rectum (APER) for rectal adenocarcinoma and
their effects on time to healing. PATIENTS AND METHODS: We studied all cases of
APER performed in our unit by four consultants over 7 years. Seven out of nine
factors considered important in wound healing were analysed using logistic
regression and a multivariate model was built to examine interactions. Wound
persistence was calculated using the Kaplan-Meier method. RESULTS: Data were
available for 94 of 96 patients [male:female, 3:2, median age 72.5 (IQR: 64-78)].
Thirty-nine (41%) patients had 25 Gray, 3-portal, fractionated 5-day short course
preoperative radiotherapy (SCPRT). Dukes stages were A (34%), B (26%), C (40%).
Perineal wound complications occurred in 44 (47%), 16% of these requiring return
to theatre. Local recurrences occurred in 13 (15%). There was no evidence to
suggest that either patient gender, age, smoking status, preoperative albumin or
haemoglobin level, or T stage were associated with the development of wound
complications. The odds of wound complications for a patient who had SCPRT was
over 10 times that for a patient who did not have preoperative radiotherapy (odds
ratio 10.15, 95% CI: 3.80-27.05, n = 94). Seventy-four per cent of SCPRT and 96%
of non-SCPRT wounds had healed by 1 year. Estimated failed wound healing rates at
30 and 90 days were 64% (95% CI: 46-78) and 48% (95% CI: 30-64) in SCPRT patients
compared with 23% (95% CI: 12-35) and 9% (95% CI: 3-20) in non-SCPRT patients
(log rank test P < 0.0001). CONCLUSION: Patients who have an APER are over 10
times more likely to have a perineal wound complication if they have SCPRT than
not. Two-thirds of these will not have healed by 1 month, half by 3 months and
over a quarter will still remain unhealed at 1 year. This has important
implications for patient management decisions. Large prospective studies are
needed to evaluate the effects of a selective policy for radiotherapy
administered to patients requiring APER.
PMID- 17032321
TI - Long-term results of surgically treated traumatic rectourethral fistulas.
AB - OBJECTIVE: Rectourethral fistulas are uncommon, usually iatrogenic injuries that
are demanding to treat. We present the challenging problems involving the
treatment of rectourethral fistulas caused by war wounds. MATERIALS AND METHODS:
In the period 1991-1996, during the war in Croatia and Bosnia, six patients with
rectourethral fistulas caused by war injuries were operated in our institution by
the same surgeon. All patients were young males with a mean age of 24.6 years. In
all patients, double diversion (diversion colostomy and cystostomy) was performed
at the time of the injury in military hospitals. In three patients, multiple
unsuccessful operations were performed in other institutions to close
rectourethral fistula. We found urethrocystography and proctoscopy as the most
reliable diagnostic studies and performed them in all patients. In first three
patients, we performed transanal repair with anterior rectal wall advancement
flap. Because it failed in all three patients, we performed York-Mason trans
sphincteric approach and anterior rectal wall advancement flap after which
rectourethral fistula closed in all patients. Because of the satisfactory
results, we performed the same procedure in other three patients. RESULTS: In all
patients rectourethral fistula healed 2 months after the operation. Closure of
diverting colostomy was performed after urethrocystography and proctoscopy proved
that the rectourethral fistula has healed. There were no operative deaths and no
major complications. Urethral stenosis developed in one patient and was
successfully managed by dilatation. CONCLUSION: We believe that York-Mason trans
sphincteric approach offers straightforward access through healthy tissues and
good fistula visualization. Anterior rectal wall advancement flap can easily be
performed and offer good chances for definitive closure of the rectourethral
fistula.
PMID- 17032322
TI - A single common urgent pathway for all colorectal referrals reduces time to
diagnosis and treatment.
AB - OBJECTIVE: Guidelines for the urgent referral of patients with suspected
colorectal cancer were introduced in 2000. They aimed to facilitate the prompt
diagnosis and treatment of patients with symptoms suggestive of malignant
disease. Recent assessment of these guidelines has suggested that although they
identify 9-14% of patients with colorectal cancer, they may be used
inappropriately and may lead to delays in treatment for those patients with
cancers whose symptoms do not fit the guidelines. We aimed to assess the effect
of introducing a single pathway for all referrals irrespective of indicated
urgency. METHOD: All referral letters to a single consultant colorectal surgeon
over a 6-month period were coded 'urgent' irrespective of the indicated urgency
on the original referral letter. Data was collected prospectively on 47 patients
diagnosed with colorectal cancer identified over the trial period. Patient
demographics, the mode of presentation, urgency of referral and waiting times
were documented. RESULTS: Following the introduction of the common urgent
referral pathway, no patient waited longer than 62 days from referral to
treatment or 31 days from the decision to treat to first treatment, thus meeting
government targets introduced in 2005. CONCLUSION: The introduction of the urgent
referral guidelines has accelerated the referral pathway for patients with
symptoms suggestive of colorectal cancer, although this is at the expense of the
majority of patients who present via conventional pathways. The introduction of a
common urgent pathway allows prompt diagnosis and treatment and is of particular
benefit for the majority of patients not referred via the 2-week standard. Until
a more accurate method of identifying the highest risk patients is implemented,
we suggest that all patients are seen on an urgent basis.
PMID- 17032323
TI - Magnetic resonance imaging pelvimetry in 186 patients with rectal cancer confirms
an overlap in pelvic size between males and females.
AB - INTRODUCTION: It has generally been considered that open pelvic surgery is almost
always easier in female subjects because of anatomical differences facilitating
surgical access. In contrast, the male pelvis has been considered to be narrower
and deeper. The objective of this study was to assess magnetic resonance imaging
(MRI) pelvimetry in patients with rectal cancer in whom any difference in
pelvimetry may potentially affect operative management. Male and female pelvic
bony dimensions were compared. METHOD: A cohort of 186 patients (112 males and 74
females) with rectal cancer who had been recruited prospectively to the Magnetic
Resonance Imaging and Rectal Cancer European Equivalence Study (MERCURY Study)
were assessed. Complete digital images were available on these patients. A
comparison of the pelvic dimensions was made between the sexes using 16
dimensions measured on the MRI workstation using the mid-sagittal and axial
images. RESULTS: There was no significant difference and considerable overlap
between the sexes with respect to each of the 14 parameters measured from the
preoperative sagittal MRI scan. However, there was a highly significant
difference between the interspinous and intertuberous transverse diameter of the
pelvis (P < 0.0001). CONCLUSION: Outcome after surgery may be influenced by the
technical difficulty of the operation and this had been thought to be partly
affected by the pelvic size. In this cohort of 186 patients, the only difference
seen between the sexes, was in the transverse mid-inlet and pelvic outlet
diameter.
PMID- 17032324
TI - Management of intersphincteric abscesses.
AB - OBJECTIVE: Intersphincteric abscesses are relatively rare, and in some cases of
upward extensions in the supralevator plane, can be difficult to manage. The aim
of this study was to analyse the type of treatment used in these abscesses.
METHODS: Twenty-one intersphincteric abscesses treated by endoanal drainage in
our colorectal unit between 1992 and 2004 were reviewed from our database;
location and extension of the abscess, type of treatment and recurrence rates and
the use of endoanal ultrasound were studied. RESULTS: Ninety per cent of patients
were male; 10 had a previous history of surgery for perianal abscess and
suppuration (48%); 16 (76%) had a posterior location and five were anterolateral.
Twelve patients had low intersphincteric abscesses and were treated by laying
open the abscess and dividing the internal sphincter. Nine were found to have
high extensions into the intermuscular planes and were treated by staged
procedures: a temporary transanal mushroom catheter was used in seven patients.
Endoanal ultrasound was used initially in seven patients (33.3%) and for the
evaluation of definitive treatment in 11 (52%). CONCLUSIONS: Low intersphincteric
abscesses should be treated by de-roofing of the abscess and division of the
internal sphincter up to a level of the dentate line. High intersphincteric
abscesses are relatively frequent and mostly require staged surgery with a
temporary mushroom (de Pezzer) catheter. Accurate anatomical ultrasound
localization and proper drainage become important to avoid recurrences or
extrasphincteric fistulas.
PMID- 17032325
TI - Anxieties should not be forgotten when screening relatives of colorectal cancer
patients by colonoscopy.
AB - OBJECTIVE: Individuals with a strong family history have a high risk of
developing colorectal cancer. They could well benefit from targeted screening and
their increased risk warrants an invasive procedure such as colonoscopy. This
study aims to assess the anxieties of symptom-free relatives offered screening by
colonoscopy. METHOD: A simple questionnaire was sent to 50 consecutive people who
had colorectal cancer screening by colonoscopy because of a strong family
history. RESULTS: Forty-five questionnaires were answered. On assessing their
anxiety levels before and after colonoscopy, 56% noticed an improvement after the
test, 33% were still as anxious and 11% had raised anxiety levels despite
screening. Although most of the screening colonoscopies were normal, 44% of
asymptomatic relatives undergoing invasive screening had no improvement of their
cancer anxieties. CONCLUSION: Screening people with a strong family history of
colorectal cancer may be an efficient, cost-effective and focussed way of
detecting early neoplasms rather than screening the general population. Using
colonoscopy alone however, a large proportion of people still have cancer
anxieties after being screened. This small study suggests that in order to
attempt to alleviate anxieties, a colonoscopy alone is insufficient for some in
this high-risk group.
PMID- 17032326
TI - A prospective evaluation of occult disorders in obstructed defecation using the
'iceberg diagram'.
AB - OBJECTIVE: Surgical treatment of constipation and obstructed defecation (OD)
carries frequent recurrences, as OD is an 'iceberg syndrome' characterized by
'underwater rocks' or occult diseases which may affect the outcome of surgery.
The aim of this study was to evaluate occult disorders in order to alert the
clinician of these and minimize failures. METHOD: One hundred consecutive
constipated patients with OD symptoms, 81 female patients, median age 52 years,
underwent perineal examination, proctoscopy, anorectal manometry, and
anal/vaginal ultrasound. Anorectal physiology and imaging tests were also carried
out when indicated, as well as psychological and urogynaecological consultation.
Symptoms were graded using a modified 1-20 constipation score. Both evident (e.g.
rectocele) and occult (e.g. anismus) diseases were prospectively evaluated using
a novel 'iceberg diagram'. The type of treatment, whether conservative or
surgical, was also recorded. RESULTS: Fifty-four (54%) patients had both mucosal
prolapse and rectocele. All patients had at least two occult OD-related diseases,
66 patients had at least three: anxiety-depression, anismus and rectal
hyposensation were the most frequent (66%, 44% and 33% respectively). The median
constipation score was 11 (range 2-20), the median number of 'occult disorders'
was 5 (range 2-8). Conservative treatment was carried out in most patients.
Surgery was carried out in 14 (14%) patients. CONCLUSION: The novel 'iceberg
diagram' allowed the adequate evaluation of OD-related occult diseases and better
selection of patients for treatment. Most were managed conservatively, and only a
minority were treated by surgery.
PMID- 17032327
TI - Do supervised colorectal trainees differ from consultants in terms of quality of
TME surgery?
AB - OBJECTIVE: The quality of surgical excision is held to be a major determinant of
outcome following surgery for rectal cancer. Macroscopic examination of the
excised mesorectum allows for reproducible assessment of the quality of surgery.
We aimed to determine whether quality of excision undertaken by colorectal
trainees under supervision was comparable with that performed by consultants, as
measured using mesorectal grades. METHOD: A total of 130 consecutive patients
undergoing potentially curative resection for primary adenocarcinoma of the
rectum in our centre from 2001 to 2003 were included in the study. The
pathologists graded the excised mesorectum according to staged classification
proposed by Quirke. The outcome (quality of mesorectal excision and secondary
outcomes including local recurrence and overall recurrence) of operations
performed by consultants was compared with that of trainees. Statistical
significance was tested using Pearson chi(2) test. RESULTS: Eighty-nine
operations were performed by consultants and 41 by senior colorectal trainees
with consultant supervision. Forty-four patients (49%) had good mesorectum when
operated by consultants in comparison with 17 (41.5%) by the trainees. There was
no statistically significant difference (P = 0.717) between the two groups in
terms of quality of mesorectum excised after potentially curative resection.
Furthermore, there were seven local recurrences in patients operated by
consultants (7.8%) when compared with four in the trainee group (9.5%) and once
again there was no statistical significance between the two groups (P = 0.719).
CONCLUSION: We conclude that the quality of rectal cancer excision, as defined by
mesorectal grades, achieved by supervised colorectal trainees is comparable with
that achieved by consultants.
PMID- 17032328
TI - Transanal endoscopic microsurgery: risk factors for local recurrence of benign
rectal adenomas.
AB - OBJECTIVE: Transanal endoscopic microsurgery (TEM) is a minimally invasive
technique for excision of selected benign and malignant rectal neoplasms. It is
considered a safe and effective treatment but recurrence rates of 1-13% are
reported for benign lesions. The aim of this study was to assess risk factors for
local recurrence of benign rectal lesions and to evaluate mortality and morbidity
following TEM. METHOD: Data were prospectively collected from all patients
undergoing TEM for benign adenomas from January 1998 to March 2005. The procedure
was performed by a single surgeon and patients were regularly followed up.
RESULTS: One hundred and forty-six procedures were included, with a median
patient age of 74 years (range 22-92 years). The mean lesion area was 16 cm(2)
(range 0.3-150 cm(2)) and the median distance from the dentate line was 9 cm
(range 0-17 cm). Immediate complications included bleeding (six) and acute
urinary retention (six). There has been one (0.68%) procedure-related death.
After a median follow up of 39 months (range 4-89 months) there have been seven
recurrences (4.8%), recurring at a mean time of 23.3 months (range 5-48 months).
Only microscopic involvement of the circumferential resection margin was found to
be significantly associated with recurrence (P = 0.0059). Recurrence was not
associated with age, size of lesion, previous treatment, severity of dysplasia or
use of the harmonic scalpel. CONCLUSION: TEM is a safe and effective treatment
for benign rectal adenomas. Circumferential resection margin involvement is
associated with recurrence, which tends to occur late. Therefore extended follow
up is recommended.
PMID- 17032329
TI - The clinical significance of the circumferential resection margin following
preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common
language.
AB - OBJECTIVE: The presence of microscopic tumour cells within 1 mm of the
circumferential surgical resection margin (CRM) is the endpoint most strongly
associated with local recurrence in rectal cancer and doubles the risk of
developing distant metastases. Reporting on the CRM can monitor surgical quality
assurance and over the past two decades has driven advances in surgical technique
with the increasing use of total mesorectal excision. The aim of this review was
to use the evidence from both phase II and phase III randomized trials of
preoperative radiotherapy and chemoradiation in rectal cancer, to assess how
often CRM involvement is currently documented and examine its utility as an early
predictor of both disease-free and overall survival. METHOD: A literature search
identified both randomized and nonrandomized trials of preoperative radiation
therapy and chemoradiation therapy in rectal cancer since 1993. The aim was to
find those studies, which documented the distance from the periphery of the
tumour and the CRM. Small trials treating < 20 patients were excluded. RESULTS:
One hundred and eighty-seven phase II and 28 phase III trials of preoperative
radiotherapy or chemoradiation were identified. Most trials documented the degree
of response but only 10 of 187 phase II/retrospective studies and four of 28
phase III trials presented data on the achievement of a negative CRM. Few defined
this early pathological endpoint prospectively with accurate measurements.
However, the majority of studies did use the definition of 400 and in Sf 12-400 fractions were markedly increased at 6 h.
Postprandial cholesterol content of RLPs (RLP-C) correlated with respective
triglycerides in Sf > 400 (r = 0.737) and Sf 12-400 (r = 0.857), apoB-48 in Sf >
400 (r = 0.710) and Sf 12-400 (r = 0.664), apoB-100 in Sf > 400 (r = 0.812) and
Sf 12-400 (r = 0.533). RLP-C correlated with oxLDL both in fasting and in fed
state (r = 0.482 and r = 0.543, respectively) and inversely with LDL size (r =
0.459 and r = -0.442, respectively). (P < 0.001 for all). OxLDL was elevated
postprandially (P < 0.001). In multivariate analysis, oxLDL was a determinant of
severity and extent of CAD. CONCLUSION: Postprandial state is associated with
oxidative stress. The magnitude of oxLDL increases during alimentary lipaemia and
is associated with coronary atherosclerosis.
PMID- 17032344
TI - Copeptin, a fragment of the vasopressin precursor, as a novel predictor of
outcome in heart failure.
AB - BACKGROUND: Natriuretic peptides, particularly brain natriuretic peptide (BNP),
are elevated in heart failure and therefore considered to be excellent predictors
of outcome. Vasopressin is also known to be related to the severity of heart
disease. Copeptin--an inactive fragment of the vasopressin precursor--has not
been previously investigated in the context of heart failure. MATERIALS AND
METHODS: We prospectively studied 268 patients with advanced heart failure after
they had been discharged from the hospital. We investigated the ability of BNP
and copeptin to predict death, re-hospitalization due to heart failure, and a
combination of the two endpoints. RESULTS: Over a mean follow-up period of 15.8
months (up to 24 months), 83 patients died, 122 patients experienced worsening of
heart failure, and 145 patients achieved the combined endpoint. Univariate
predictors of death were copeptin, BNP, age and impaired kidney function. In
multivariate analysis, copeptin (chi(2) = 16, P < 0.0001) and age (chi(2) = 4, P
< 0.05) were independent predictors. Univariate predictors of re-hospitalization
due to heart failure were copeptin, BNP, age and impaired kidney function.
Furthermore, in multivariate analysis BNP (chi(2) = 18, P < 0.0001), age (chi(2)
= 11.8, P < 0.001) and copeptin (chi(2) = 4.2, P < 0.05) were found to be
independent predictors. CONCLUSION: Our study is the first to show that copeptin
is an excellent predictor of outcome in advanced heart failure patients. Its
value is superior to that of BNP in predicting death and a combined endpoint,
although BNP is still suitable for predicting chronic heart failure (CHF) re
hospitalization. Our data imply that vasopressin antagonism might be a new target
to improve outcome in this population.
PMID- 17032345
TI - Paraoxonase and arylesterase activities in coronary artery disease.
AB - BACKGROUND: Paraoxonase-1 is an enzyme with three activities which are inversely
related to cardiovascular diseases. Accordingly, the aim of the study was to
investigate the paraoxonase, arylesterase activities and oxidative/anti-oxidative
status in coronary artery disease (CAD) and their correlation with the extent of
CAD. MATERIALS AND METHODS: Study populations of 193 patients with
angiographically documented CAD, 83 patients with normal coronary angiograms
(NCAD) and 55 healthy volunteers were included in the study. The patients with
CAD were divided into three categories according to the number of diseased
coronaries. Also, a Gensini score was calculated for each patient. Serum
paraoxonase and arylesterase activities were measured spectrophotometrically.
Oxidative and anti-oxidative status was evaluated by measuring serum lipid
hydroperoxide (LOOH), total anti-oxidant status (TAS) and free sulfhydryl groups
(-SH = total thiol). Lipid parameters were determined by routine laboratory
methods. RESULTS: Serum paraoxonase and arylesterase activities, TAS and -SH
levels were lower in the CAD group compared with the NCAD group and control group
(P < 0.05, all). Serum LOOH levels of the CAD group were greater than those in
both the control and NCAD groups (P < 0.05). The major decreases in paraoxonase,
arylesterase activities, -SH and TAS levels and the major increase in LOOH levels
were observed in the 3-vessels disease group. In multiple linear regression
analysis, the Gensini score was independently correlated with paraoxonase
activity (beta = -0.469, P < 0.001), -SH levels (beta = -0.232, P < 0.001), HDL
levels and history of diabetes. CONCLUSIONS: Both paraoxonase activity and -SH
levels are independently associated with the presence and extent of CAD. Reduced
paraoxonase activity and -SH levels may play a role in the severity of coronary
atherosclerosis.
PMID- 17032346
TI - Hypercholesterolaemia alters the responses of the plasma lipid profile and
inflammatory markers to supplementation of the diet with n-3 polyunsaturated
fatty acids from fish oil.
AB - BACKGROUND: The influence of supplementing the diet with long-chain n-3
polyunsaturated fatty acids (PUFA) from fish oil on plasma lipids and lipid
peroxides and the production of pro-inflammatory mediators in normolipidaemic and
hypercholesterolaemic rats were studied. MATERIALS AND METHODS: Rats were divided
into four groups and fed one of the following diets: a control diet (containing
4% corn oil); an n-3 PUFA diet [containing 4% eicospentaenoic (EPA) +
docosahexaenoic (DHA)]; a hypercholesterolaemic diet (HCH); or a HCH + n-3 PUFA
diet over a 4-week period. Plasma lipids, lipid peroxides, cytokines [tumour
necrosis factor (TNF)alpha, interleukin (IL)-6, interferon (IFN)gamma] and mRNA
for hepatic nuclear factor-4alpha (HNF4alpha) were determined. RESULTS: Plasma
triglyceride (TG), but not cholesterol, levels were decreased by the n-3 PUFA as
compared with the control diet (P < 0.001), but the addition of n-3 PUFA to the
HCH diet decreased both the TG (P < 0.01) and cholesterol (P < 0.05)
concentrations. Plasma lipid peroxides and expression HNF4alpha mRNA were
increased by n-3 PUFA in the normolipidaemic (P < 0.05), but not in the
hyperlipidaemic rats. Compared with the control diet group, plasma concentrations
of TNFalpha and IL-6 were increased in the n-3 PUFA (P < 0.05) and HCH diet (P <
0.05, P < 0.01, respectively) groups, but not in animals given the HCH + n-3 PUFA
diet, whereas IFNgamma levels were increased in hypercholesterolaemia (P < 0.05),
but were unaffected by n-3 PUFA. CONCLUSION: These results demonstrate that the
major effect of fish oil n-3 PUFA is to lower the TG levels in both normo- and
hyperlipidaemia. Furthermore, in the hypercholesterolaemic state, fish oil n-3
PUFA induces additional beneficial changes in the immune and peroxidation
responses.
PMID- 17032347
TI - Assessing progression to impaired glucose tolerance and type 2 diabetes mellitus.
AB - BACKGROUND: A prospective evaluation of the relationship between insulin
secretion and insulin sensitivity, derived from the fasting state, is needed in
clinical practice in order to identify the worsening of glucose metabolism. In
this study the authors examine whether the product of insulin sensitivity and
insulin secretion, assessed from the fasting state, predicts progression from
normal glucose tolerance (NGT) to impaired fasting glucose (IFG) and from
impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM). MATERIALS
AND METHODS: A cohort of 300 subjects with NGT and 75 subjects with IGT were
followed up over a 5-year period. Insulin sensitivity was calculated using the
Belfiore index (B) and insulin secretion by the homeostasis model analysis beta
cell (HOMA-beta cell) index: the product of B-beta is expressed as: (40 x Ins(0)
pmol L(-1))/Glu(0) mmol L(-1){[(Glu(0) mmol L(-1)x Ins(0) pmol L(-1)) + 1] -
3.5[(Glu(0) mmol L(-1) x Ins(0) pmol L(-1)) - 1]}, where Glu(0) is fasting
glucose and Ins(0) is fasting insulin. RESULTS: From baseline at the end of the
follow-up period, the product B-beta decreased 10.7% and 52.2% in progressors to
IGT and T2DM, respectively. The product B-beta predicts the progression from NGT
to IGT [relative risk (RR) 2.7, CI(95%) 1.2-9.1] and from IGT to T2DM (RR 5.3,
CI(95%) 1.3-8.55). The cut-off point for the product B-beta that better predicts
progression from NGT to IGT is 0.25 (sensitivity 88%, specificity 92%) and from
IGT to T2DM 0.15 (sensitivity 92%, specificity 95%). CONCLUSIONS: Adaptation of
insulin secretion to compensate for decreased insulin sensitivity during
transition to IGT and T2DM can be successfully assessed with simple measures
derived from the fasting state. The product B-beta predicts the development to
IGT and T2DM.
PMID- 17032348
TI - Randomized comparison of two rescue therapies for Helicobacter pylori infection.
AB - BACKGROUND: Bismuth salts are not available worldwide. It remains unknown whether
clarithromycin can replace bismuth salts as an adjuvant agent in the rescue
regimens for Helicobacter pylori infection. We therefore designed the prospective
study to compare the efficacies of two rescue therapies for H. pylori infection
after standard triple therapies. PATIENTS AND METHODS: Ninety-three patients who
failed H. pylori eradication using proton pump inhibitor plus clarithromycin and
amoxicillin were randomly assigned to undergo rescue therapy with esomeprazole,
clarithromycin, tetracycline and metronidazole (ECTM group, n = 46) or
esomeprazole, bismuth subcitrate, tetracycline and metronidazole (EBTM group, n =
47). Follow-up endoscopy was performed at 8 weeks after the end of treatment to
assess the treatment response. RESULTS: Intention-to-treat analysis demonstrated
both groups had similar eradication rates (ECTM 74% vs. EBTM 77%; P = 0.76) and
drug compliance (ECTM 94% vs. EBTM 96%; P = 0.68). However, the frequency of
adverse events in the ECTM group was higher than that in EBTM group (ECTM 57% vs.
EBTM 36%, P = 0.05). In the EBTM group, eradication rate of metronidazole
resistant strains was lower than that of metronidazole-susceptible strains
(67%[8/12] vs. 100%[9/9], P = 0.05). However, eradication rates were similar
between metronidazole-susceptible and metronidazole-resistant strains in ECTM
group (69%[9/13] vs. 70%[7/10], P = 1.00). CONCLUSIONS: The new ECTM second-line
therapy can achieve similar eradication rate as standard EBTM therapy. It may be
very useful in countries where bismuth salts are not available.
PMID- 17032349
TI - Urodilatin and four cardiac hormones decrease human renal carcinoma cell numbers.
AB - BACKGROUND: Mortality from renal-cell cancer remains a significant problem with
an estimated 12,600 deaths in the United States in 2005 even with current
treatment(s) of surgery, chemotherapy, radiation and immunotherapy. Four cardiac
natriuretic peptides, that is, atrial natriuretic peptide, vessel dilator, long
acting natriuretic peptide and kaliuretic peptide have significant anti-cancer
effects in breast, pancreatic, prostate and colon adenocarcinomas. MATERIALS AND
METHODS: These four peptide hormones plus brain natriuretic peptide (BNP), C
natriuretic peptide (CNP) and urodilatin, a peptide hormone formed in the kidney
by a different post-translational processing of the atrial natriuretic peptide
prohormone, were evaluated for their anti-cancer effects in renal carcinomas.
RESULTS: Dose-response curves revealed a significant (P < 0.0001) decrease in
human renal carcinoma cells with each 10-fold increase in concentration from 1
microm to 100 microm of five of these peptide hormones. There was an 81%, 74%,
66%, 70% and 70% elimination within 24 h in renal carcinoma cells secondary to
vessel dilator, kaliuretic peptide, urodilatin, atrial natriuretic peptide and
long-acting natriuretic peptide, respectively (P < 0.0001 for each), whereas BNP
had no effect and CNP decreased renal cancer cell number by 10% (P = 0.04) at
their 100 microm concentrations. Three days after treatment with these peptide
hormones, the cancer cells began to proliferate again. The four cardiac hormones
and urodilatin decreased DNA synthesis from 65-84% (P < 0.00001), whereas BNP and
CNP decreased DNA synthesis 3% and 12% (both non-significant). Western blots
revealed for the first time natriuretic peptide receptors (NPR)-A, -B and -C were
present in the renal cancer cells. CONCLUSIONS: These results indicate that
urodilatin and the four cardiac hormones have potent anti-cancer effects by
eliminating up to 81% of renal carcinoma cells within 24 h of treatment.
PMID- 17032350
TI - Brain site-specific gene expression analysis in Alzheimer's disease patients.
AB - BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disorder
that is characterized by a progressive loss of higher cognitive functions. The
brain of an individual with AD exhibits extracellular senile plaques (SPs) of
aggregated amyloid-beta peptide (Abeta) and intracellular neurofibrillary tangles
(NFTs). Given the critical role of neuronal transport of both proteins and
organelles, it is not surprising that perturbation of microtubule-based transport
may play a major role in the pathogenesis of AD. MATERIALS AND METHODS: We used
the cDNA subtraction methodology and in vitro neural cell culture analyses to
study the meaning of the brain site-specific gene expression pattern in cerebral
tissue obtained from AD patients and also from control subjects at autopsy.
RESULTS: We observed that cytoskeleton-associated proteins were down-regulated in
AD subjects. We also noted an altered expression of the microtubule-associated
protein 1B (MAP1B), the heat-shock protein (HSP)-90 (a key chaperone molecule),
the tripartite motif-containing proteins (TRIM)-32/37 (an anti apoptotic enzyme
with ubiquitin-protein ligase activity) and the Reticulon-3 (a modulator of the
amyloid-precursor-protein (APP) cleavage) in AD brains. Additional molecular- and
cell-biological studies revealed that small interfering RNA (siRNA)-mediated down
regulation of MAP1B expression leads to neuronal cell death in vitro. CONCLUSION:
Altered expression of MAP1B, HSP90, TRIM32/37 and Reticulon-3 provides new clues
by which the ubiquitin-proteasome-, the protein-chaperon- and the APP-processing
systems are disturbed in AD, thus, leading to neuritic amyloid plaques and
neurofibrillary tangles.
PMID- 17032351
TI - Acute lung injury following pancreas ischaemia-reperfusion: role of xanthine
oxidase.
AB - BACKGROUND: Acute pancreatitis can lead to increased pulmonary vascular
permeability and respiratory failure. Oxidants (and their generator, xanthine
oxidase (XO)) play an important role in injuring the structural integrity of the
pulmonary epithelium and endothelium, but their importance in the induction of
acute lung injury following pancreas ischaemia-reperfusion (IR) has not been
defined. MATERIALS AND METHODS: Rats (n = 48) received a regular or a tungsten
(oxidoreductase inhibitor)-enriched diet for 14 days. Their isolated pancreases
were then either perfused (controls) or made ischaemic (IR) for 40 min (12
replicates/group). This was followed by in-series pancreas plus normal isolated
lung reperfusion for 15 min. Lungs only were subsequently perfused with the 15
min accumulated pancreas effluents for 45 min. RESULTS: Injury was induced in all
IR pancreases as expressed by reperfusion pressure, wet-to-dry ratio and amylase
and lipase concentrations. Tissue XO activity was high and reduced glutathione
pool was low in the tungsten-free IR pancreases. Pulmonary plateau pressure
increased by 46% and final PO(2)/FiO(2) decreased by 24%. Capillary pressure and
weight rose two- to fourfold in lungs paired with IR non-treated pancreases.
Twofold increases in bronchoalveolar lavage volume and contents, including XO,
were also recorded in this group of lungs. Lungs exposed to tungsten-treated
ischaemic pancreas effluents were minimally damaged and tissue XO content was low
compared to controls. CONCLUSIONS: Ex-vivo acute pancreatitis induces acute lung
injury via oxidants/antioxidants misbalance, which may be prevented by
attenuating pancreas oxidative stress.
PMID- 17032352
TI - Distinct but critical roles for integrin alphaIIbbeta3 in platelet lamellipodia
formation on fibrinogen, collagen-related peptide and thrombin.
AB - Integrins are the major receptor type known to facilitate cell adhesion and
lamellipodia formation on extracellular matrix proteins. However, collagen
related peptide and thrombin have recently been shown to mediate platelet
lamellipodia formation when presented as immobilized surfaces. The aims of this
study were to establish if there exists a role for the platelet integrin
alpha(IIb)beta(3) in this response; and if so, whether signalling from the
integrin is required for lamellipodia formation on these surfaces. Real-time
analysis was used to compare platelet morphological changes on surfaces of
fibrinogen, collagen-related peptide or thrombin in the presence of various
pharmacological inhibitors and platelets from 'knockout' mice. We demonstrate
that collagen-related peptide and thrombin stimulate distinct patterns of
platelet lamellipodia formation and elevation of intracellular Ca(2+) to that
induced by the integrin alpha(IIb)beta(3) ligand, fibrinogen. Nevertheless,
lamellipodia formation on collagen-related peptide and thrombin is dependent upon
engagement of alpha(IIb)beta(3), consistent with release of alpha(IIb)beta(3)
ligand(s) from platelet granules. However, the requirement for signalling by the
integrin on fibrinogen can be bypassed by the addition of thrombin to the
solution. These observations reveal a critical role for alpha(IIb)beta(3) in
forming lamellipodia on collagen-related peptide and thrombin which is dependent
on its ability to function as an adhesive receptor but not necessarily on its
ability to signal. These results suggest that integrins may play an important
role in lamellipodia formation triggered by nonintegrin ligands in platelets and
possibly in other cell types.
PMID- 17032353
TI - Leadzyme formed in vivo interferes with tobacco mosaic virus infection in
Nicotiana tabacum.
AB - We developed a new method for inhibiting tobacco mosaic virus infection in
tobacco plants based on specific RNA hydrolysis induced by a leadzyme. We
identified a leadzyme substrate target sequence in genomic tobacco mosaic virus
RNA and designed a 16-mer oligoribonucleotide capable of forming a specific
leadzyme motif with a five-nucleotide catalytic loop. The synthetic 16-mer RNA
was applied with nontoxic, catalytic amount of lead to infected tobacco leaves.
We observed inhibition of tobacco mosaic virus infection in tobacco leaves in
vivo due to specific tobacco mosaic virus RNA cleavage effected by leadzyme. A
significant reduction in tobacco mosaic virus accumulation was observed even when
the leadzyme was applied up to 2 h after inoculation of leaves with tobacco
mosaic virus. This process, called leadzyme interference, is determined by
specific recognition and cleavage of the target site by the RNA catalytic strand
in the presence of Pb(2+).
PMID- 17032354
TI - Isoquinoline-1,3,4-trione and its derivatives attenuate beta-amyloid-induced
apoptosis of neuronal cells.
AB - Caspase-3 is a programmed cell death protease involved in neuronal apoptosis
during physiological development and under pathological conditions. It is a
promising therapeutic target for treatment of neurodegenerative diseases. We
reported previously that isoquinoline-1,3,4-trione and its derivatives inhibit
caspase-3. In this report, we validate isoquinoline-1,3,4-trione and its
derivatives as potent, selective, irreversible, slow-binding and pan-caspase
inhibitors. Furthermore, we show that these inhibitors attenuated apoptosis
induced by beta-amyloid(25-35) in PC12 cells and primary neuronal cells.
PMID- 17032355
TI - The interaction of disturbances and small mammal community dynamics in a lowland
forest in Belize.
AB - 1. Three floods (July 2000, August 2002, September 2003) and a hurricane (October
2001) that occurred in a lowland forest in the southern Maya Mountains of Belize
presented an opportunity to evaluate the influence of these disturbances on the
structure of a small mammal assemblage. 2. Four terrestrial and four primarily
scansorial/arboreal species were trapped July 2000-March 2005 in six grids over
14 irregularly spaced trapping periods. 3. Community dynamics were characterized
more by changes in species composition than changes in diversity. The dynamics
were driven by species-specific variation in abundance, with changes in
composition generally, but not exclusively, due to the occurrence or
disappearance of species at low abundance. Despite the disturbances, species
richness remained relatively constant. Evenness within the assemblage was
consistently low, primarily as a result of dominance by one species, Heteromys
desmarestianus. 4. Effects of flooding on community structure were direct but
relatively brief (< 1 year), and varied with the duration and intensity of
flooding. Effects from the hurricane were indirect but long-lasting and strongly
related to severely reduced food resources. 5. This study suggests that long-term
dynamics in the structure of many animal communities in the tropics often results
from interactions between direct and indirect effects of disturbance. It also
suggests that community resistance will depend on variation in disturbance type
and regime, but resilience will be determined by the life-history characteristics
of each species.
PMID- 17032356
TI - Dynamics of mutualist populations that are demographically open.
AB - 1. Few theoretical studies have examined the impact of immigration and emigration
on mutualist population dynamics, but a recent empirical study (A.R. Thompson
Oecologia, 143, 61-69) on mutualistic fish and shrimp showed that immigration can
prevent population collapse, and that intraspecific competition for a mutualistic
partner can curb population expansion. To understand in a theoretical context the
implications of these results, and to assess their generality, we present a two
species model that accounts explicitly for immigration and emigration, as well as
distinguishing the impacts of mutualism on birth rates, death rates and habitat
acquisition. 2. The model confirms that immigration can stabilize mutualistic
populations, and predicts that high immigration, along with enhanced reproduction
and/or reduced mortality through mutualism, can cause population sizes to
increase until habitat availability curbs further expansion. 3. We explore in
detail the effects of different forms of habitat limitation on mutualistic
populations. Habitat availability commonly limits the density of both populations
if mutualists acquire shelter independently. If a mutualist depends on a partner
for habitat, densities of that mutualist are capped by the amount of space
provided by that partner. The density of the shelter-provider is limited by the
environment. 4. If a mutualism solely augments reproduction, and most locally
produced individuals leave the focal patch, then the mutualism will have a
minimal effect on local dynamics. If the mutualism operates by reducing rates of
death or enhancing habitat availability, and there is at least some immigration,
then mutualism will affect local dynamics. This finding may be particularly
relevant in marine systems, where there is high variability (among species and
locations) in the extent to which progeny disperse from natal locations. 5.
Overall, our results demonstrate that the consequences of immigration and
emigration for the dynamics of mutualists depend strongly on which demographic
rate is influenced by mutualism. 6. By relating our model to a variety of
terrestrial and aquatic systems, we provide a general framework to guide future
empirical studies of the dynamics of mutualistic populations.
PMID- 17032357
TI - Effect of emergent aquatic insects on bat foraging in a riparian forest.
AB - 1. Riparian zones serve several ecological functions for bats. They provide a
source of prey and likely provide favourable structural habitats and shelter from
predators. Many studies have shown that bats use the space above streams, ponds
or riparian vegetation as feeding habitat. These studies, however, have never
distinguished between the effects of habitat structure and prey availability on
the foraging activities of bats. Such effects can only be distinguished by an
experimental approach. We predicted that bat activity along a stream is
influenced by the number of emerged aquatic insects. 2. We evaluated the response
of terrestrial consumers, insectivorous bats, to changes in the abundance of
emergent aquatic insects by conducting a manipulative field experiment. In a
deciduous riparian forest in Japan, aquatic insect flux from the stream to the
riparian zone was controlled with an insect-proof cover over a 1.2 km stream
reach. 3. We estimated the abundance of emergent aquatic and flying terrestrial
arthropods near the treatment and control reaches using Malaise traps. The
foraging activity of bats was evaluated in both treatment and control reaches
using ultrasonic detectors. 4. The insect-proof cover effectively reduced the
flux of emergent aquatic insects to the riparian zone adjacent to the treatment
reach. Adjacent to the control reach, adult aquatic insect biomass was highest in
spring, and then decreased gradually. Terrestrial insect biomass increased
gradually during the summer at both treatment and control reaches. 5. Foraging
activity of bats was correlated with insect abundance. In spring, foraging
activity of bats at the control reach was significantly greater than at the
treatment reach, and increased at both sites with increasing terrestrial insect
abundance. 6. Our result suggests that the flux of aquatic insects emerging from
streams is one of the most important factors affecting the distribution of
riparian-foraging bats. As is the case with other riparian consumers, resource
subsidies from streams can directly enhance the performance or population density
of riparian-dependent bats. To conserve and manage bat populations, it is
important to protect not only forest ecosystems, but also adjacent aquatic
systems such as streams.
PMID- 17032358
TI - From plankton to top predators: bottom-up control of a marine food web across
four trophic levels.
AB - 1. Abundant mid-trophic pelagic fish often play a central role in marine
ecosystems, both as links between zooplankton and top predators and as important
fishery targets. In the North Sea, the lesser sandeel occupies this position,
being the main prey of many bird, mammal and fish predators and the target of a
major industrial fishery. However, since 2003, sandeel landings have decreased by
> 50%, and many sandeel-dependent seabirds experienced breeding failures in 2004.
2. Despite the major economic implications, current understanding of the
regulation of key constituents of this ecosystem is poor. Sandeel abundance may
be regulated 'bottom-up' by food abundance, often thought to be under climatic
control, or 'top-down' by natural or fishery predation. We tested predictions
from these two hypotheses by combining unique long-term data sets (1973-2003) on
seabird breeding productivity from the Isle of May, SE Scotland, and plankton and
fish larvae from the Continuous Plankton Recorder survey. We also tested whether
seabird breeding productivity was more tightly linked to sandeel biomass or
quality (size) of individual fish. 3. The biomass of larval sandeels increased
two- to threefold over the study period and was positively associated with
proxies of the abundance of their plankton prey. Breeding productivity of four
seabirds bringing multiple prey items to their offspring was positively related
to sandeel larval biomass with a 1-year lag, indicating dependence on 1-year-old
fish, but in one species bringing individual fish it was strongly associated with
the size of adult sandeels. 4. These links are consistent with bottom-up
ecosystem regulation and, with evidence from previous studies, indicate how
climate-driven changes in plankton communities can affect top predators and
potentially human fisheries through the dynamics of key mid-trophic fish.
However, the failing recruitment to adult sandeel stocks and the exceptionally
low seabird breeding productivity in 2004 were not associated with low sandeel
larval biomass in 2003, so other mechanisms (e.g. predation, lack of suitable
food after metamorphosis) must have been important in this case. Understanding
ecosystem regulation is extremely important for predicting the fate of keystone
species, such as sandeels, and their predators.
PMID- 17032359
TI - Population limitation of the northern red-backed vole in the boreal forests of
northern Canada.
AB - 1. Across the vast boreal forests of North America, no population cycles in
Clethrionomys species occur. In Eurasia, by contrast, some Clethrionomys
populations of the same species undergo regular 3-5-year cycles. We examined the
effects of nutrients, food, competitors, predators and climate on population
limitation in the northern red-backed vole (Clethrionomys rutilus Pallas) in the
south-western Yukon to determine why this difference occurs. 2. From 1986 to 1996
we added food, reduced large mammal predators and excluded snowshoe hares (Lepus
americanus Erxleben) from large plots and found that none of these manipulations
affected red-backed vole abundance. Adding nutrients as nitrogen, phosphorus and
potassium (NPK) fertilizer had a slight negative effect, probably acting through
a reduction in dwarf shrub productivity caused by competition from grasses. 3. We
monitored weasel populations directly through trapping and indirectly through
snow tracking. Predation by these vole specialists was irrelevant as a limiting
factor most of the time because voles in this area do not reach the densities
needed to sustain weasel populations. Other boreal forest mammal and bird
predators did not focus on red-backed voles. However, when red-backed vole
populations increased in the forest and Microtus voles also increased in the
meadows, weasel populations increased and may have temporarily depressed red
backed voles in winter. 4. We monitored one major potential food, white spruce
seeds, but seed fall was not related to population changes in red-backed voles,
even after mast years. 5. We assessed the impact of weather variables, and the
average depth of the snow pack during winter (October-March) was correlated
directly with vole demography, having both direct effects in that year and
delayed effects in the following year. 6. Our long-term trapping data (1973-96)
indicate that Clethrionomys populations fluctuated, with peaks following hare
peaks by 2-3 years. 7. We propose that the key variable limiting these vole
populations is overwinter survival, and this is a function of overwinter food
from berries produced during the previous summer by dwarf shrubs. These shrubs
may be stimulated by abundant moisture from winter snows or by periodic
fertilization from large quantities of pellets produced at snowshoe hare peaks.
PMID- 17032360
TI - Prediction of bird-day carrying capacity on a staging site: a test of depletion
models.
AB - 1. The carrying capacity of a site for migratory water birds, expressed in bird
days, can be of particular conservation value. Several attempts have been made to
model this carrying capacity using ideal free distribution models such as, for
instance, depletion models, in which the distribution is fully determined by
exploitative competition. 2. In the tests of depletion models carried out so far,
no alternative models were compared; rather, one specific model was tested. We
tested whether bird-days were more in accordance with birds depleting the food
resource (a1) until a critical food density which just enabled survival or (a2)
until a threshold food density which renders the site as profitable as an
alternative site; and birds (b1) satisfying their daily requirements or (b2)
maximizing daily intake. 3. We studied Bewick's swans feeding on below-ground
tubers of fennel pondweed in one part of an autumn staging site. In most years
between 1995 and 2005, we measured tuber biomass densities around September,
November and March, and counted swans daily during their stopover in October. 4.
The best fit between observed and predicted bird-days was obtained by assuming
that the swans were maximizing their daily intake and depleting the tubers until
a threshold biomass density (which yielded the same energetic return as the
alternative food source after accounting for a small part of the initial tuber
biomass being out of reach of the swans). Also in line with daily intake
maximization, the daily feeding time did not differ from 10 h day(-1), the value
predicted for Bewick's swans based on their feeding costs. 5. Our results
suggests that the applicable model to calculate carrying capacity may depend
strongly on whether birds use a site to stopover or to winter, because it
determines whether the birds are more likely to use a threshold or critical food
density, and to behave as energy maximizers or satisficers.
PMID- 17032361
TI - Why do female migratory birds arrive later than males?
AB - 1. In migratory birds males tend to arrive first on breeding grounds, except in
sex-role reversed species. The two most common explanations are the rank
advantage hypothesis, in which male-male competition for breeding sites drives
stronger selection for early arrival in males than females, and the mate
opportunity hypothesis, which relies on sexual selection, as early arrival
improves prospects of mate acquisition more for males than for females. 2. To
date, theoretical work has focused on selection for early arrival within a single
sex, usually male. However, if fitness depends on territory quality, selection
for early arrival should operate on both sexes. Here we use two independent
modelling approaches to explore the evolution of protandry (male-first arrival)
and protogyny (female-first arrival) under the rank advantage and mate
opportunity hypotheses. 3. The rank advantage hypothesis, when operating alone,
fails to produce consistent patterns of protandry, despite our assumption that
males must occupy territories before females. This is because an individual of
either sex benefits if it out-competes same-sex competitors. Rather than
promoting protandry, the rank advantage mechanism can sometimes result in
protogyny. Female-female competition is stronger than male-male competition early
in the season, if females compete for a resource (territories occupied by males)
that is initially less common than the resource of interest to males (unoccupied
territories). 4. Our results support the mate opportunity hypothesis as an
explanation of why protandry is the norm in migratory systems. Male-biased adult
sex ratios and high levels of sperm competition (modelled as extra-pair young:
EPY) both produce protandry as a result of sexual selection. Protogyny is only
observed in our models with female-biased sex ratios and low EPY production. 5.
We also show that the effects of sex ratio biases are much stronger than those of
EPY production, explore the evidence for sex ratio biases and extra-pair
paternity in migratory species and suggest future research directions.
PMID- 17032362
TI - Determinants of quality in a long-lived colonial species.
AB - 1. In many animal populations a small proportion of individuals produce the
majority of surviving offspring, but the underlying mechanisms are unclear.
Behaviour may be an important determinant of variation in fitness: 'high-quality'
individuals may have enhanced abilities in foraging or predator and parasite
avoidance. 2. The role of behaviour in determining variation in quality was
examined using the common guillemot Uria aalge, a monogamous seabird with
biparental care. Using a novel mixed model approach, we analysed binary data on
breeding success of each pair attempting to breed in each year with variables
critical to breeding success (timing of breeding; inferred age; breeding
experience and success; number of nest sites and partners) as fixed effects.
Random effects for year, male, female and each distinct pairing of a male and a
female were included in the model, allowing a quality estimate to be derived for
each individual and pair. A range of behaviours associated with breeding were
examined in relation to these quality estimates. 3. Breeding success declined
with timing of breeding, and increased initially with age before declining in old
age. It increased with previous successful experience, not breeding experience
per se, until senescence effects became apparent. For males, breeding success
declined with increasing numbers of mates. 4. The most important behavioural
determinants of quality operated at the level of the pair, with the time mates
spent together at the site and chick feeding rates both positively related to
quality. At the individual level, trip durations and feeding rates were
associated with female but not male quality, suggesting that pair quality was
operating principally through the female. However, removal of laying date, the
most important component in the binomial model, confirmed that the pair effect
was much larger than the female effect. 5. This study demonstrates the potential
of mixed modelling to determine quality estimates based on long-term breeding
histories. The probability of a successful reproductive attempt was explained by
the timing of breeding, age, successful breeding experience and number of mates.
Behaviour was an important proximate mechanism underlying quality, in particular
the foraging abilities of the pair, and the female's contribution to offspring
provisioning. In species with biparental care, behavioural correlates of quality
operate most strongly at the scale of the breeding pair, because contributions
from both individuals are required for a successful outcome.
PMID- 17032363
TI - Density dependence and the control of helminth parasites.
AB - 1. The transient dynamics and stability of a population are determined by the
interplay between species density, its spatial distribution and the positive and
negative density-dependent processes regulating population growth. 2. Using the
human-helminth parasite system as an example, we propose that the life-stage upon
which negative density dependence operates will influence the rate of host
reinfection following anthelmintic chemotherapy, and the likely success of
control programmes. 3. Simple deterministic models are developed which highlight
how a parasite species whose population size is down-regulated by density
dependent establishment will reinfect a host population at a faster rate than a
species with density-dependent parasite fecundity. 4. Different forms of density
dependence can produce the same equilibrium behaviour but different transient
dynamics. Under-representing the nature and magnitude of density-dependent
mechanisms, and in particular those operating upon establishing life-stages, may
cause the resilience of the parasite population to a control perturbation to be
underestimated.
PMID- 17032364
TI - The role of group size and environmental factors on survival in a cooperatively
breeding tropical passerine.
AB - 1. Variation in survival, a major determinant of fitness, may be caused by
individual or environmental characteristics. Furthermore, interactions between
individuals may influence survival through the negative feedback effects of
density dependence. Compared to species in temperate regions, we have little
knowledge about population processes and variation in fitness in tropical bird
species. 2. To investigate whether variation in survival could be explained by
population size or climatic variables we used capture-recapture models in
conjunction with a long-term data set from an island population of the
territorial, cooperatively breeding Seychelles warbler (Acrocephalus
sechellensis). The lack of migration out of the study population means that our
results are not confounded by dispersal. 3. Annual survival was high, both for
adults (84%) and juveniles (61%), and did not differ between the sexes. Although
there was significant variation in survival between years, this variation could
not be explained by overall population size or weather variables. 4. For
territorial species, resource competition will work mainly on a local scale. The
size of a territory and number of individuals living in it will therefore be a
more appropriate measure of density than overall population density.
Consequently, both an index of territory quality per individual (food
availability) and local density, measured as group size, were included as
individual covariates in our analyses. 5. Local density had a negative effect on
survival; birds living in larger groups had lower survival probabilities than
those living in small groups. Food availability did not affect survival. 6. Our
study shows that, in a territorial species, although density-dependent effects
might not be detectable at the population level they can be detected at the
individual territory level - the scale at which individuals compete. These
results will help to provide a better understanding of the small-scale processes
involved in the dynamics of a population in general, but in particular in
tropical species living in relatively stable environments.
PMID- 17032365
TI - Are ectoparasite communities structured? Species co-occurrence, temporal
variation and null models.
AB - 1. We studied temporal variation in the structure of flea communities on small
mammalian hosts from eastern Slovakia using null models. We asked (a) whether
flea co-occurrences in infracommunities (in the individual hosts) in different
hosts as well as in the component communities (in the host species) demonstrate a
non-random pattern; (b) whether this pattern is indicative of either positive or
negative flea species interactions; (c) whether this pattern varies temporally;
and (d) whether the expression of this pattern is related to population size of
either fleas or hosts or both. 2. We constructed a presence/absence matrix of
flea species for each temporal sample of a host species and calculated four
metrics of co-occurrence, namely the C-score, the number of checkerboard species
pairs, the number of species combinations and the variance ratio (V-ratio). Then
we compared these metrics with the respective indices calculated for 5000 null
matrices that were assembled randomly using two algorithms, namely fixed-fixed
(FF) and fixed-equiprobable (FE). 3. Most co-occurrence metrics calculated for
real data did not differ significantly from the metrics calculated for simulated
matrices using the FF algorithm. However, the indices observed for 42 of 75
presence/absence matrices differed significantly from the null expectations for
the FE models. Non-randomness was detected mainly by the C-score and V-ratio
metrics. In all cases, the direction of non-randomness was the same, namely the
aggregation, not competition, of flea species in host individuals and host
species. 4. The inclusion or exclusion of the uninfested hosts in the FE models
did not affect the results for individual host species. However, exclusion of the
uninfested host species led to the acceptance of the null hypothesis for only six
of 13 temporal samples of the component flea communities for which non-randomness
was detected when the uninfested hosts were included in the analysis. 5. In most
host species, the absolute values of the standardized size effect of both the C
score and V-ratio increased with an increase in host density and a concomitant
decrease in flea abundance and prevalence. 6. Results of this study demonstrated
that (a) flea assemblages on small mammalian hosts were structured at some times,
whereas they appeared to be randomly assembled at other times; (b) whenever non
randomness of flea co-occurrences was detected, it suggested aggregation but
never segregation of flea species in host individuals or populations; and (c) the
expression of structure in flea assemblages depended on the level of density of
both fleas and hosts.
PMID- 17032366
TI - Reproductive performance in grey seals: age-related improvement and senescence in
a capital breeder.
AB - 1. Three hypotheses have been advanced to account for age-related improvement in
performance: the selection hypothesis predicts improved due to the loss of lower
quality phenotypes, the constraint hypothesis predicts individuals improve
function, and the restraint hypothesis predicts younger individuals forego or
reduce effort because of mortality risks. A decline in age-related performance
(i.e. senescence) is predicted by mutation accumulation, antagonistic pleiotropy
and disposable soma (wear and tear) hypotheses. 2. Using five measures of
performance - birth rate, maternal and pup birth mass, pup weaning mass, weaning
success and lactation length - we tested these hypotheses concerning age-related
change in reproduction in 279 female grey seals (Halichoerus grypus), ages 4-42
years, over a 23-year period between 1983 and 2005 on Sable Island, Nova Scotia.
These females produced 2071 pups. 3. Although body mass of primiparous females
increased with age (4-7 years) birth mass of their pups did not, but pup weaning
mass did. Second- and third-parity females of the same age as primiparous females
gave birth to and weaned heavier pups. However, parity and age were dropped from
models when maternal body mass was included. 4. The proportion of females giving
birth varied significantly with maternal age, increasing in young females and
then declining late in life. Weaning success rate also increased rapidly to about
8 years and subsequently declined in females > 32 years. 5. Generalized additive
models indicated nonlinear changes in 3 day body mass (i.e. approximately birth
mass) and weaning mass of pups as a function of maternal age, after accounting
statistically for the effects of maternal body mass. Mixed-effects, repeated
measures models fitted to longitudinal data further supported the conclusion that
pup birth mass and weaning mass vary nonlinearly with maternal age and indicated
nonlinear changes in lactation duration. 6. We found some support for the
constraint hypothesis, but our findings were not consistent with the selection
hypothesis or the restraint hypothesis as the basis for improvement in
reproductive performance. 7. Senescence was evident in multiple female and
offspring traits, indicating the degeneration in function of several
physiological systems as predicted by the disposable soma hypothesis.
PMID- 17032367
TI - Income breeding allows an aquatic snake Seminatrix pygaea to reproduce normally
following prolonged drought-induced aestivation.
AB - 1. Capital breeding is an ideal reproductive strategy for many ectotherms because
it provides a disassociation between feeding and reproduction, a necessary
requirement for animals that become anorexic during pregnancy. Among ectotherms,
some viviparous snakes (e.g. Viperidae) exemplify the capital breeding strategy
because many species (i) do not feed during pregnancy due to behavioural
conflicts between reproduction and foraging, and (ii) take more than one season
to accumulate sufficient energetic stores for reproduction. 2. Isolated wetlands
often exhibit extreme annual fluctuations in environmental conditions with
prolonged droughts periodically leaving wetlands completely dry and devoid of
prey. Following droughts, however, wetlands can be extremely productive,
rendering prey resources virtually unlimited for some species. 3. This study
examines drought survival strategy and reproductive ecology of a small aquatic
snake Seminatrix pygaea (Cope) in an isolated wetland. Seminatrix pygaea are
atypical from most sympatric snake species in that (i) their small body size,
reliance on aquatic prey, and high rates of evaporative water loss make them ill
suited to overland movement, and (ii) they may not be subject to costs typically
associated with feeding during pregnancy. 4. We hypothesized that S. pygaea would
survive periodic multiyear droughts by aestivating within the dried wetland, a
survival strategy heretofore undocumented in snakes. Further, we hypothesized
that if S. pygaea rely on 'typical' snake reproductive strategies of 'adaptive
anorexia' and capital breeding, reproductive output would be reduced in the first
wet year following drought. 5. By encircling a 10-ha wetland with a continuous
drift fence before it refilled we were able to demonstrate that S. pygaea were
present within the dried wetland prior to the onset of spring rains that refilled
the wetland in 2003. Our results suggest that S. pygaea are capable of surviving
multiyear droughts by aestivating within the dried wetland. 6. Despite having
presumably depleted energy reserves during the drought, S. pygaea reproduced with
the same frequency and fecundity during the first season following refilling of
the wetland as in pre-drought years. 7. The ability of S. pygaea to rebound
rapidly from the stresses of prolonged drought is due in part to their
reproductive ecology. Seminatrix pygaea readily feed throughout pregnancy and
consequently can rapidly translate high prey abundances into reproductive output
through income breeding.
PMID- 17032368
TI - A test of the reproductive cost hypothesis for sexual size dimorphism in Yarrow's
spiny lizard Sceloporus jarrovii.
AB - 1. Trade-offs between reproduction and growth are central assumptions of life
history theory, but their implications for sexual size dimorphism (SSD) are
poorly understood. 2. Adult male Yarrow's spiny lizards Sceloporus jarrovii
average 10% larger than adult females. In a low-altitude (1700 m) population,
this SSD develops because males grow more quickly than females during the first
year of life, particularly during the first female reproductive season. This
study tests the hypothesis that SSD develops because female growth is constrained
by energetic costs of reproduction. 3. To test for a growth cost of reproduction,
I compared growth rates of free-living females that differed, either naturally or
experimentally, in reproductive status. Females that naturally delayed
reproduction until their second year grew more quickly than females that
reproduced as yearlings, and ovariectomized yearlings grew more quickly and to
larger sizes than reproductive controls. 4. To determine whether SSD develops in
the absence of this inferred reproductive cost, I also studied a high-altitude
(2500 m) population in which all females delay reproduction until their second
year. Sex differences in growth trajectories were similar to those observed at
low altitude, such that males averaged 10% larger than females even prior to
female reproduction. 5. Although female growth may be constrained by
reproduction, multiple lines of evidence indicate that this cost is insufficient
to explain the full magnitude of SSD in S. jarrovii. First, differences in growth
of reproductive and nonreproductive females are not observed until the final
month of gestation, by which time SSD is already well developed. Second, the
growth benefit accruing from experimental inhibition of reproduction accounts for
only 32% of the natural sex difference in body size. Finally, SSD develops well
in advance of female reproduction in a high-altitude population with delayed
maturation.
PMID- 17032369
TI - Experimental evidence that the introduced fire ant, Solenopsis invicta, does not
competitively suppress co-occurring ants in a disturbed habitat.
AB - 1. The fire ant, Solenopsis invicta, is a globally distributed invasive ant that
is largely restricted to disturbed habitats in its introduced range. For more
than half a century, biologists have believed its success results from superior
competitive abilities relative to native ant species, as well as an escape from
their natural enemies. 2. We used large volumes of hot water to kill fire ant
colonies, and only fire ant colonies, on experimental plots in pastures, and
found that populations and diversity of co-occurring ants did not subsequently
increase. 3. These results are contrary to classical predictions and indicate
that S. invicta is not a superior competitor that suppresses native ants, and
that the low diversity and abundance of native ants in degraded ecosystems does
not result from interaction with fire ants. Instead, other factors such as prior
disturbance and recruitment limitation may be the primary limiting factors for
native species in these habitats.
PMID- 17032370
TI - The contributions of age and sex to variation in common tern population growth
rate.
AB - 1. The decomposition of population growth rate into contributions from different
demographic rates has many applications, ranging from evolutionary biology to
conservation and management. Demographic rates with low variance may be pivotal
for population persistence, but variable rates can have a dramatic influence on
population growth rate. 2. In this study, the mean and variance in population
growth rate (lambda) is decomposed into contributions from different ages and
demographic rates using prospective and retrospective matrix analyses for male
and female components of an increasing common tern (Sterna hirundo) population.
3. Three main results emerged: (1) subadult return was highly influential in
prospective and retrospective analyses; (2) different age-classes made different
contributions to variation in lambda: older age classes consistently produced
offspring whereas young adults performed well only in high quality years; and (3)
demographic rate covariation explained a significant proportion of variation in
both sexes. A large contribution to lambda did not imply a large contribution to
its variation. 4. This decomposition strengthens the argument that the
relationship between variation in demographic rates and variation in lambda is
complex. Understanding this relationship and its consequences for population
persistence and evolutionary change demands closer examination of the lives, and
deaths, of the individuals within populations within species.
PMID- 17032371
TI - Distribution of a naturally fluctuating ungulate population among heterogeneous
plant communities: ideal and free?
AB - 1. Herbivore distribution is often assumed to follow the ideal free distribution
(IFD) model. This assumes that organisms are omniscient about forage quality and
availability within the area available to them and are free to move, with
negligible cost, throughout this environment. If this were the case we would
expect that, at lowest densities, all animals would be found in the best habitat
patches, with less desirable habitats being occupied stepwise as population
density increases. We test this using data from a naturally fluctuating
population of feral Soay sheep. 2. We show that, although the distribution of
individuals is correlated positively with food quality, in line with patterns
reported for hill sheep in Scotland, their distribution does not conform to the
predictions of the IFD model. We argue that it is the dynamic nature of their
food resource that causes this departure from the predictions of the IFD model
and make the case that the IFD model, in its unmodified form, is inappropriate
for use in modelling distribution among patches containing dynamic resources.
PMID- 17032372
TI - Effects of sampling regime on the mean and variance of home range size estimates.
AB - 1. Although the home range is a fundamental ecological concept, there is
considerable debate over how it is best measured. There is a substantial
literature concerning the precision and accuracy of all commonly used home range
estimation methods; however, there has been considerably less work concerning how
estimates vary with sampling regime, and how this affects statistical inferences.
2. We propose a new procedure, based on a variance components analysis using
generalized mixed effects models to examine how estimates vary with sampling
regime. 3. To demonstrate the method we analyse data from one study of 32
individually marked roe deer and another study of 21 individually marked
kestrels. We subsampled these data to simulate increasingly less intense sampling
regimes, and compared the performance of two kernel density estimation (KDE)
methods, of the minimum convex polygon (MCP) and of the bivariate ellipse
methods. 4. Variation between individuals and study areas contributed most to the
total variance in home range size. Contrary to recent concerns over reliability,
both KDE methods were remarkably efficient, robust and unbiased: 10 fixes per
month, if collected over a standardized number of days, were sufficient for
accurate estimates of home range size. However, the commonly used 95% isopleth
should be avoided; we recommend using isopleths between 90 and 50%. 5. Using the
same number of fixes does not guarantee unbiased home range estimates:
statistical inferences differ with the number of days sampled, even if using KDE
methods. 6. The MCP method was highly inefficient and results were subject to
considerable and unpredictable biases. The bivariate ellipse was not the most
reliable method at low sample sizes. 7. We conclude that effort should be
directed at marking more individuals monitored over long periods at the expense
of the sampling rate per individual. Statistical results are reliable only if the
whole sampling regime is standardized. We derive practical guidelines for field
studies and data analysis.
PMID- 17032373
TI - Interactive effects of environmental stress and inbreeding on reproductive traits
in a wild bird population.
AB - 1. Conservation biologists are concerned about the interactive effects of
environmental stress and inbreeding because such interactions could affect the
dynamics and extinction risk of small and isolated populations, but few studies
have tested for these interactions in nature. 2. We used data from the long-term
population study of song sparrows Melospiza melodia on Mandarte Island to examine
the joint effects of inbreeding and environmental stress on four fitness traits
that are known to be affected by the inbreeding level of adult birds: hatching
success, laying date, male mating success and fledgling survival. 3. We found
that inbreeding depression interacted with environmental stress to reduce
hatching success in the nests of inbred females during periods of rain. 4. For
laying date, we found equivocal support for an interaction between parental
inbreeding and environmental stress. In this case, however, inbred females
experienced less inbreeding depression in more stressful, cooler years. 5. For
two other traits, we found no evidence that the strength of inbreeding depression
varied with environmental stress. First, mated males fathered fewer nests per
season if inbred or if the ratio of males to females in the population was high,
but inbreeding depression did not depend on sex ratio. Second, fledglings
survived poorly during rainy periods and if their father was inbred, but the
effects of paternal inbreeding and rain did not interact. 6. Thus, even for a
single species, interactions between the inbreeding level and environmental
stress may not occur in all traits affected by inbreeding depression, and
interactions that do occur will not always act synergistically to further
decrease fitness.
PMID- 17032374
TI - Cowpox virus infection in natural field vole Microtus agrestis populations:
delayed density dependence and individual risk.
AB - 1. Little is known about the dynamics of pathogen (microparasite) infection in
wildlife populations, and less still about sources of variation in the risk of
infection. Here we present the first detailed analysis of such variation. 2.
Cowpox virus is an endemic sublethal pathogen circulating in populations of wild
rodents. Cowpox prevalence was monitored longitudinally for 2 years, in
populations of field voles exhibiting multiannual cycles of density in Kielder
Forest, UK. 3. The probability that available susceptible animals seroconverted
in a given trap session was significantly positively related to host density with
a 3-month time lag. 4. Males were significantly more likely to seroconvert than
females. 5. Despite most infection being found in young animals (because
transmission rates were generally high) mature individuals were more likely to
seroconvert than immature ones, suggesting that behavioural or physiological
changes associated with maturity contribute to variation in infection risk. 6.
Hence, these analyses confirm that there is a delayed numerical response of
cowpox infection to vole density, supporting the hypothesis that endemic
pathogens may play some part in shaping vole cycles.
PMID- 17032375
TI - Variations on a theme: sources of heterogeneity in the form of the interspecific
relationship between abundance and distribution.
AB - 1. A positive interspecific relationship between abundance and distribution is
widely considered to be one of the most general patterns in ecology. However, the
relationship appears to vary considerably across assemblages, from significant
positive to significant negative correlations and all shades in between. 2. This
variation has led to the suggestion that the abundance-distribution relationship
has multiple forms, with the corollary that different patterns may inform about,
or have different, causes. However, this variation has never been formally
quantified, nor has it been determined whether the observed variation is
indicative of sampling error in estimating a single effect or of real
heterogeneity in such relationships. Here, we use the meta-analytical approach to
assess variation in abundance-distribution relationships, and to test different
hypotheses for it. 3. Analysis of 279 relationships found a mean effect size of
0.655, which was both highly significantly different from zero and indicative of
a strong positive association between abundance and distribution. However, effect
sizes were highly heterogeneous, supporting the contention that this relationship
does indeed have multiple forms. 4. Most notably, relationships vary
significantly in strength across realms, with the strongest in the marine and
intertidal, intermediate relationships for terrestrial and parasitic assemblages,
and the weakest relationships in freshwater systems. Effect sizes in all of the
aquatic realms are homogeneous, suggesting that realm is an important source of
the heterogeneity observed across all studies. We posit that this may be because
the different spatial structure of the environment in each realm affects the
opportunity for the dispersal of individuals between sites. 5. Some of the
remaining heterogeneity in effect sizes for terrestrial assemblages could be
explained by partitioning assemblages by habitat, scale, biogeographical region
and taxon, but considerable heterogeneity in effect sizes for terrestrial and
parasitic assemblages remained unexplained.
PMID- 17032376
TI - Habitat exploration and use in dispersing juvenile flying squirrels.
AB - 1. Variation in behaviours involved in habitat selection is important for several
evolutionary and ecological processes. For example, habitat use during dispersal
may differ from breeding habitat use, and for dispersers the scale of habitat
familiarity is determined by exploratory behaviour. We studied habitat use and
exploration of 56 radio-collared juvenile flying squirrels Pteromys volans L.
within natal home range and during dispersal, and compared habitat use between
juveniles and 37 adults within breeding home range. 2. Before dispersal, young
flying squirrels actively moved around the natal site. Surprisingly, long
distance dispersers explored less than short-distance dispersers, but philopatric
individuals explored similar distances as dispersers. Females explored less than
males, although females are the more dispersive sex in flying squirrels. 3. For
most of the individuals the settlement area was unfamiliar due to long dispersal
distance. Consequently, direction and distance of exploration were not very
strong predictors of settlement location. However, individuals familiar with the
settlement area concentrated exploration to that area. Exploration did not
correlate with short-term survival. 4. Dispersers preferred breeding habitat
while dispersing, but were found more often in matrix habitat than juveniles
within natal, or adults within breeding, home ranges. 5. We conclude that
familiarity does not determine settlement as much as, for example, availability
of the habitat for flying squirrels. Based on our results, it also seems clear
that data on adult habitat use are not enough to predict habitat use of
dispersing individuals. In addition, our results support the recent view that
short- and long-distance dispersers may need to be analysed separately in
ecological and evolutionary analyses.
PMID- 17032377
TI - Functional imaging of carotid atheromatous plaques.
AB - Atherosclerotic plaque rupture within the internal carotid artery is an important
cause of transient ischemic attack (TIA) and stroke. Conventional imaging
techniques such as ultrasound and angiography provide information about the
structural consequences of such plaques in terms of luminal stenosis. Most
clinical trials of carotid surgery and stenting and based on these imaging
methods. Techniques aimed at imaging the biological 'functional' status of the
plaque are now emerging. Most of these are based on the premise that inflammatory
activity is an index of plaque stability. In this article we review potential
imaging targets from the known molecular biological pathways of atherosclerosis.
Both conventional imaging techniques and the newer methods are discussed. Recent
data from position emission tomography (PET) imaging and from the use of
superparamagnetic iron oxide particles with magnetic resonance (MR) imaging are
shown.
PMID- 17032378
TI - A magnetization transfer MRI study of deep gray matter involvement in multiple
sclerosis.
AB - BACKGROUND/PURPOSE: Gray matter involvement in multiple sclerosis (MS) is of
growing interest with respect to disease pathogenesis. Magnetization transfer
imaging (MTI), an advanced MRI technique, is sensitive to disease in normal
appearing white matter (NAWM) in patients with MS. DESIGN/METHODS: We tested if
MTI detected subcortical (deep) gray matter abnormalities in patients with MS (n=
60) vs. age-matched normal controls (NL, n= 20). Magnetization transfer ratio
(MTR) maps were produced from axial proton density, conventional spin-echo, 5 mm
gapless slices covering the whole brain. Region-of-interest-derived MTR
histograms for the caudate, putamen, globus pallidus, thalamus, and NAWM were
obtained. Whole brain MTR was also measured. RESULTS: Mean whole brain MTR and
the peak position of the NAWM MTR histogram were lower in patients with MS than
NL (P < .001) and mean whole brain MTR was lower in secondary progressive (SP, n=
10) than relapsing-remitting (RR, n= 50, P < .001) patients. However, none of the
subcortical gray matter nuclei showed MTR differences in MS vs. NL, RR vs. SP, or
SP vs. NL. CONCLUSIONS: The MTI technique used in this cohort was relatively
insensitive to disease in the deep gray matter nuclei despite showing sensitivity
for whole brain disease in MS. It remains to be determined if other MRI
techniques are more sensitive than MTI for detecting pathology in these areas.
PMID- 17032379
TI - Dynamic vascular analysis shows a hyperemic flow pattern in sickle cell disease.
AB - BACKGROUND: By the age of 20 years, 10% of sickle cell disease (SCD) patients
have experienced a stroke. It is unclear if SCD stroke is due primarily to
hemodynamic effects of intracranial stenosis, or metabolic failure from anemia.
Transcranial Doppler ultrasound (TCD) identifies a SCD subgroup with high stroke
risk, but high mean flow velocity (MFV) can be due to stenosis or high flow rate,
as with metabolic hyperemia of severe anemia. Dynamic Vascular Analysis (DVA; New
Health Sciences, Inc., Bethesda, MD) is a new way to analyze TCD data, with
potential to separate structural from metabolic causes of high MFV. METHODS:
Eighty SCD patients, regardless of hemoglobin genotypes, aged 2 to 22 years,
without clinical stroke or transient ischemic attack (TIA), who had TCD (1/1/02
to 1/1/04) as part of routine outpatient clinical follow-up, with both the TCD
report and study videotape available, were included. Waveforms were reviewed and
marked by protocol, and DVA indices calculated including MFV, pulsatility index
(PI), systolic acceleration (SA), dynamic flow index (DFI), dynamic pressure
index (DPI), and dynamic compliance index (DCI). Mean and standard deviation were
defined for the whole group, and for four subgroups, by age. RESULTS: MFV, DFI,
and DPI were highest at 6- to 9-year-olds, declining thereafter. The 14- to 22
year-old group was also compared to a group of healthy young athletes (15- to 22
years old). SCD patients had higher MFV, lnSA, DFI, DPI, and lower PI and DCI in
most segments, suggesting global hyperemia. CONCLUSION: This is the first report
of cross-sectional results of DVA in a cohort of SCD outpatients without prior
clinical stroke (TIA). These results suggest hyperemia without significant focal
intracranial stenosis. There were also differences between asymptomatic SCD and
young athletes, and the MFV, DFI, and DPI were highest at the age of 6 to 9
years, decreasing as age increased.
PMID- 17032380
TI - Diagnostic accuracy of MRI for middle cerebral artery stenosis: a postmortem
study.
AB - BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) has been widely applied
in detecting intracranial large artery stenosis, but there have been few
validation studies to compare with histopathology. The aim of the postmortem
study is to assess the accuracy of MRI in identifying middle cerebral artery
(MCA) stenosis. METHODS: We recruited, consecutively, Chinese postmortem
autopsies in our hospital during 19 months. MRI was performed in the postmortem
brains to scan the cross-sections of MCAs with barium expanding the artery lumen.
The MCAs were then removed for histopathologic studies. With histopathology as a
reference standard, the accuracy of MRI was evaluated, and the correlation
between MCA stenosis identified by MRI and radiologically or histopathologically
evident brain infarcts was investigated. RESULTS: Seventy-six consecutive
autopsies were recruited. The sensitivity and specificity of MRI in detecting
more than 30% MCA stenosis were 38.6% and 92.2%, with a positive predictive value
of 87.2% and negative predictive value of 52.2%, and the corresponding values of
MRI in identifying more than 50% MCA stenosis were 57.1%, 90.8%, 50%, and 83.0%,
respectively. Both more than 30% and more than 50% MCA stenosis identified by MRI
were found to be associated with infarctions in the corresponding MCA territory
(P= 0.001, odds ratio = 4.365, 95% CI: 1.684-11.313; and P= 0.039, odds ratio =
2.694, 95% CI: 1.139-6.377). CONCLUSIONS: Our study demonstrates the agreement
between ex vivo MRI and histopathology in identifying MCA stenosis, and the
correlation between the MCA stenosis identified by MRI and radiologically or
histopathologically evident brain infarcts.
PMID- 17032381
TI - Derivation of power M-mode transcranial Doppler criteria for angiographic proven
MCA occlusion.
AB - BACKGROUND: Stringent transcranial Doppler (TCD) criteria for diagnosing
occlusion are needed for more reliable TCD performance at bedside in the acute
stroke setting. SUBJECTS AND METHODS: At three academic stroke centers, we
performed TCD examination for patients with symptoms of cerebral ischemia who
underwent digital subtraction angiography (DSA). We used a standard insonation
protocol with power M-mode Doppler (PMD) TCD (TCD 100 M, Spencer Technologies
Inc., Seattle, WA). We collected mean flow velocity (MFV), pulsatility indices
(PI), and power M-mode resistance signature (absent, high, or low) in symptomatic
middle (MCA), anterior (ACA), posterior (PCA), and in affected (a), ipsilateral
(i), and contralateral (c-lat) cerebral arteries. Ratios of aMCA/c-lat MCA,
aMCA/iACA, and aMCA/iPCA MFV were subsequently calculated. PMD-TCD flow findings
were evaluated with a receiver-operating characteristic (ROC) analysis for
angiographically proven MCA occlusion. RESULTS: We studied 120 patients with
acute cerebral ischemia with PMD-TCD examinations prior to or immediately after
DSA. Lower aMCA velocities pointed to higher probability of occlusion (P= .055).
The aMCA/iPCA MFV ratio was superior to the aMCA/iACA ratio and strongly
predictive of occlusion at a threshold ratio of 0.5 (RR 2.31 CI(95) 2.13-2.51).
High resistance or absent M-mode flow signatures in the proximal MCA were present
in 87% of M1 and M2 MCA occlusions (probability 87%). In the presence of a low
resistance PMD signature, obtaining the aMCA/iPCA MFV ratio <0.5 increases
probability of occlusion to 87%. Normal MFV ratios and low-resistance M-mode
signatures are highly predictive of a negative angiogram for MCA occlusion.
CONCLUSION: In acute cerebral ischemia, reliable criteria for proximal MCA
occlusion have been developed based on combination of MFV ratios and M-mode flow
resistance signatures. Validation of these criteria will require multicenter
studies.
PMID- 17032382
TI - Patients with diffusion-perfusion mismatch on magnetic resonance imaging 48 hours
or more after stroke symptom onset: clinical and imaging features.
AB - BACKGROUND: Abnormalities in diffusion-weighted (DWI) and perfusion-weighted
(PWI) magnetic resonance imaging (MRI) are thought to reflect the presence of
brain tissue at risk for ischemic stroke. Many patients with acute ischemic
stroke have a mismatch pattern in which the PWI volume is larger than the DWI
lesion. This mismatch typically resolves over 24-48 hours. Little is known about
the presence of DWI-PWI mismatch in later stages of stroke. METHODS: This is a
retrospective study of 122 patients admitted with a diagnosis of acute ischemic
stroke who had DWI and PWI abnormalities on studies performed within 7 days of
onset of symptoms. Patients were divided into two groups: those with MRI
performed <48 hours and those with MRI performed >or=48 hours from onset of
symptoms. RESULTS: Among 42 patients with MRI performed >or=48 hours after onset
of stroke symptoms, 15 of 42 (36%) showed a mismatch pattern, compared to 45 of
80 (56%) in the <48 hours group (P < 0.05). Most of the patients in the >or=48
hours group with mismatch had large artery occlusive disease and many had
neurological fluctuations. A subset of these patients were treated with induced
hypertension and showed clinical improvement. CONCLUSIONS: Some patients have
persistent DWI-PWI mismatch up to several days after stroke onset. Further
studies are needed to determine if these patients should be candidates for
reperfusion therapy.
PMID- 17032383
TI - Stroke patients with cardiac atrial septal abnormalities: differential infarct
patterns on DWI.
AB - BACKGROUND: Stroke mechanism in patent foramen ovale (PFO) and/or atrioseptal
aneurysm (ASA) remains unclear. We aimed to study the stroke pattern on diffusion
weighted imaging (DWI), in cryptogenetic stroke according to septal
abnormalities. METHODS: We prospectively evaluated 314 cryptogenetic strokes.
Patients were categorized according to transesophageal echocardiography (TEE)
findings: PFO with ASA, PFO alone, and no abnormalities. The study group
consisted of 126 patients with acute DWI lesions within the first 7 days after
the stroke onset. We considered the presence of scattered lesions or a cortico
subcortical territorial lesion as highly suggestive of an embolic pattern.
RESULTS: PFO was identified in 77 patients (61%) and no alterations in 49
patients (39%). TEE revealed ASA in 42 patients (54.5% of PFO patients). An
"embolic" pattern was depicted in 84 (66.7%) and subcortical in 42 (33.3%). An
"embolic" pattern was significantly (P= .01) more frequently seen in PFO with ASA
patients (n= 37;44%) as compared to PFO without ASA (n= 22; 26.2%) or no
abnormalities (n= 25; 29.8%) on TEE. Univariate analysis revealed that age (P=
.06), hyperlipidemia (P= .04), degree of shunt on TEE (P= .002), and the presence
of an ASA (P= .008) were associated with an embolic pattern. After adjusting for
sex, age, and vascular risk factors, only the presence of PFO, with ASA (OR 7.27;
95% CI 1.5-35.22 P= .014) was independently associated with an embolic pattern.
CONCLUSION: In patients with cryptogenetic stroke, the presence of PFO with ASA,
but not isolated PFO, is associated with an embolic pattern on DWI. These
findings provide insights into the patho-mechanism of stroke in patients with
PFO.
PMID- 17032384
TI - Statin use is independently associated with smaller infarct volume in nonlacunar
MCA territory stroke.
AB - BACKGROUND: Studies have shown an association between HMG-CoA reductase
inhibitors (statins) and improved stroke outcomes, possibly secondary to
neuroprotective properties. OBJECTIVE: To assess whether patients taking statins
prior to ischemic stroke have smaller infarcts on magnetic resonance imaging
(MRI), adjusting for other relevant clinical factors. DESIGN: We retrospectively
reviewed the Cleveland Clinic Foundation (CCF) Neurology Inpatient Database from
June 2002 through June 2004. Demographics, medications, stroke subtype, diffusion
weighted imaging (DWI) infarct volume, admission NIHSS, and hours to MRI were
collected. Patients with a nonlacunar middle cerebral artery (MCA) territory
infarct and MRI less than 48 hours from symptom onset were included (n= 143). A
multivariable linear regression model was constructed to determine independent
predictors of smaller infarct volume. RESULTS: A total of 143 patients were
studied, including 38 patients taking statins at the time of their stroke. In
univariate analysis, patients using statins were significantly more likely to
have a history of hyperlipidemia, atrial fibrillation, and coronary artery
disease and to be using coumadin, antiplatelet drugs, and angiotensin-converting
enzyme inhibitors. Patients on statins had a tendency toward smaller infarcts in
univariate analysis (median 25.4 cm(3) vs. 15.5 cm(3), P= 0.054). In
multivariable linear regression analysis statin use, patient age, and TIA within
the prior 4 weeks were independently associated with smaller DWI volumes; vessel
occlusion on vascular imaging, and cardioembolic stroke subtype with larger
infarct size. CONCLUSIONS: Statin use prior to the onset of nonlacunar MCA
infarction was associated with a smaller infarct volume independent of other
factors. Further studies utilizing both clinical and radiologic outcomes will be
required to confirm these findings.
PMID- 17032385
TI - The thickness and texture of temporal bone in brain CT predict acoustic window
failure of transcranial Doppler.
AB - BACKGROUND AND PURPOSE: Although transcranial Doppler (TCD) is useful for
evaluation and treatment of ischemic stroke, temporal acoustic window failure
(TAWF) limits its application. We performed this study to reveal whether initial
brain CT of acute stroke patients predicted TAWF. METHODS: We performed TCD in 92
acute ischemic stroke patients (57 males, aged 38-84 years) with brain CT scans.
We measured the thickness (BTW) and evaluated the texture of the temporal bone in
acoustic windows shown in the CT scan with the use of picture archiving and
communication system. The bone mineral density (BMD) of the vertebral bodies,
femurs, and whole body was also measured. RESULTS: Doppler signals were
adequately obtained in 121 (65.8%) of the 184 middle cerebral arteries (MCA) from
both cerebral hemispheres. BTW and inhomogeneity of temporal bone, besides age,
sex, and hypercholesterolemia, was strongly correlated with TAWF. BMD was not
directly correlated with TAWF, but inhomogeneous temporal bone was correlated
with lower BMD scores. If the brain CT scan showed thick (BTW >or= 2.7 mm) and
inhomogeneous temporal bone, the possibility of TAWF was 93.5%, while if brain CT
scan showed thin (BTW < 2.7 mm) and homogenous temporal bone, it was only 5.4%.
CONCLUSIONS: The texture as well as the thickness of the temporal bone was the
most important determinant of TAWF. When acute stroke patients had thin and
homogeneous temporal bones in initial brain CT scan, TAWF was very rare, and loss
of MCA signals on TCD specifcally indicated the absence of blood flow in MCA.
PMID- 17032386
TI - Visualization of venous systems by time-of-flight magnetic resonance angiography.
AB - BACKGROUND AND PURPOSE: Time-of-flight (TOF) imaging technique depicts strong
signal from fresh unsaturated magnetization that moves fast into the imaging
region, and TOF magnetic resonance angiography (MRA) visualizes the arterial
system using saturation pulse and band. However, TOF MRA can visualize the venous
system when the flow direction is reversed. METHODS AND PATIENTS: We
consecutively enrolled patients between June 2002 and February 2003 with an
internal jugular vein (IJV) and sigmoid sinus (SS) visualized by TOF MRA. Carotid
Duplex ultrasonography was performed on all patients to check IJV flow
directions. Gadolinium (Gd)-enhanced MRA and conventional digital subtraction
angiography were performed in selected patients. RESULTS: The IJVs and SSs of
eight patients (left = 7, right = 1) were observed by TOF MRA. In these 8
patients, Duplex ultrasonography confirmed a reversed direction in IJVs. Four of
the patients underwent Gd-enhanced MRA, which showed proximal innominate vein
steno-occlusion. CONCLUSIONS: This is the first description of IJV and SS
visualization by TOF MRA. Clinical implications are discussed.
PMID- 17032387
TI - Lumbar dural ectasia secondary to spinal fusion: a report of two cases.
AB - Two cases of lumbar dural ectasia secondary to spinal fusion are presented.
Background history of dural ectasia is discussed; computed tomography (CT) and MR
imaging characteristics of dural ectasia are shown and possible causes are
discussed.
PMID- 17032388
TI - Cyberknife radiosurgery for basal skull plasmacytoma.
AB - The Cyberknife delivers frameless image-guided stereotactic radiosurgery to
intracranial and extracranial tumors. We report our use of Cyberknife
radiosurgery on a medullary plasmacytoma in the clivus extending into the foramen
magnum. No acute toxicity was seen during or within 24 hours of treatment, and
the subject had a complete and durable radiographic response on MRI 12+ months
after treatment. To our knowledge, this is a first case of successful Cyberknife
radiosurgery of a medullary plasmacytoma.
PMID- 17032389
TI - Ischemic stroke in the setting of tuberculous meningitis.
AB - The clinical syndrome of tuberculous (TB) meningitis leading to ischemic strokes
is rarely seen today in immunocompetent adults native to North America. This
entity is also notoriously difficult to diagnose because the presenting symptoms
are often nonspecific. The authors describe a case of a man with TB meningitis
which progressed to recurrent ischemic cerebral infarcts.
PMID- 17032390
TI - Differential expression of E-cadherin in metastatic lesions comparing to primary
oral squamous cell carcinoma.
AB - BACKGROUND: The main cause of treatment failure in resectable oral squamous cell
carcinoma (OSCC) is metastasis. E-cadherin (E-cad) plays a principal role in cell
adhesion and motility, and is associated with OSCC progression. The aim of this
study was to investigate the clinical significance of E-cad expression in OSCC
with lymph node metastasis which had radical neck dissection done. METHOD:
Immunohistochemistry was used to detect E-cad expression in normal oral mucosa
(NOM) (n = 10), oral precancerous lesions (OPLs) (n = 20), primary OSCC (n = 45),
and their paired metastatic lesions (n = 45). E-cad immunoreactivity correlated
with the clinicopathologic features. RESULTS: E-cadherin immunoreactivity was
progressively reduced in the NOM followed by OPLs and primary OSCC (58%). It
decreased significantly in the advanced stages of OSCC. However, the increase in
E-cad immunoreactivity was observed in the majority (60%) of metastatic lesions
in relation to primary OSCC. Patients with such increased or positive
immunoreactivity of E-cad in metastatic lesions exhibited worse prognosis.
CONCLUSION: The findings suggested a dynamic change in E-cad immunoreactivity
during tumorigenesis and metastasis of OSCC. In a multivariate analysis, E-cad
immunoreactivity in metastasis lesions (odds ratio 3.74, 95% CI 1.15-14.67; P =
0.040) implied the potential role of mortality predictors for OSCC cases with
nodal involvement.
PMID- 17032391
TI - Increased survivin expression in high-grade oral squamous cell carcinoma: a study
in Indian tobacco chewers.
AB - BACKGROUND: Oral cancer is one of the five leading sites of cancer in the Indian
population. In the present study we analyzed the expression of apoptosis
regulating genes, viz. survivin, Bcl-2, Bax and p53 in precancerous and cancerous
lesions of the buccal mucosa of Indian tobacco chewers. METHOD: Paraffin-embedded
tissue samples from 38 patients with primary oral squamous cell carcinoma (OSCC)
and 17 patients with leukoplakia were used. The expression of survivin, Bcl-2,
Bax, and p53 was evaluated using immunohistochemical staining method. RESULTS:
Thirty-six percent OSCC were found to be positive for nuclear p53 staining while
none of the precancerous lesions showed p53 positivity. Survivin, Bcl-2 and Bax
expression was found to increase with increased grade of malignancy. Increase in
survivin expression was statistically most significant (P < 0.001). CONCLUSION:
Increased expression of anti-apoptotic survivin in high-grade tumors suggests
that survivin is likely to contribute significantly to apoptosis resistance in
response to therapy.
PMID- 17032392
TI - Solitary fibrous tumor with atypical histological features occurring in the
palatine tonsil: an uncommon neoplasm in an uncommon site.
AB - Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that usually
arises in the pleura. Although this tumor has been described in other sites,
including the head and neck area, in the oropharynx it is extremely rare. We
report the first case of a SFT arising from the palatine tonsil of a 62-year-old
man. The tumor consisted of spindle-shaped cells distributed in a haphazard
pattern and presented atypical histological features such as hypercellular areas
and high mitotic count. Immunohistochemical studies showed strong positivity for
CD34 and bcl-2, and weak positivity for desmin. Smooth muscle actin, S-100
protein and cytokeratines were negative. The patient was well without disease 1
year after surgery.
PMID- 17032393
TI - Immunohistochemical detection of platelet-derived endothelial cell growth
factor/thymidine phosphorylase and angiopoietins in ameloblastic tumors.
AB - BACKGROUND: To evaluate the roles of angiogenic factors in the development and
progression of odontogenic tumors, expression of platelet-derived endothelial
cell growth factor/thymidine phosphorylase (PD-ECGF/TP) and of angiopoietins in
ameloblastic tumors as well as in tooth germs. METHODS: Tissue specimens of 11
tooth germs, 44 ameloblastomas, and five malignant ameloblastic tumors were
examined immunohistochemically with the use of antibodies against PD-ECGF/TP and
angiopoietin-1 and -2. RESULTS: Immunohistochemical reactivity for PD-ECGF/TP was
detected in mesenchymal cells in tooth germs and stromal cells in ameloblastic
tumors, and the level of immunoreactivity for PD-ECGF/TP was significantly higher
in ameloblastomas than in tooth germs. Granular cell ameloblastomas showed PD
ECGF/TP reactivity in granular neoplastic cells as well as in stromal cells.
Immunoreactivity for angiopoietin-1 and -2 was detected predominantly in
odontogenic epithelial cells near the basement membrane in tooth germs and in
benign and malignant ameloblastic tumors. Malignant ameloblastic tumors had
decreased angiopoietin-1 reactivity and ameloblastic carcinomas had increased
angiopoietin-2 reactivity as compared with the respective levels in tooth germs
and ameloblastomas. Immunohistochemical reactivity for angiopoietin-2 was
slightly higher in follicular ameloblastomas than in plexiform ameloblastomas.
CONCLUSION: Expression of PD-ECGF/TP and angiopoietin-1 and -2 in tooth germs and
ameloblastic tumors suggests that these angiogenic factors participate in tooth
development and odontogenic tumor progression by regulating angiogenesis. Altered
expression of PD-ECGF/TP and angiopoietins in ameloblastic tumors may be involved
in oncogenesis, malignant potential, and tumor cell differentiation.
PMID- 17032394
TI - Giant cell granuloma of the jawbones--a proliferative vascular lesion?
Immunohistochemical study with vascular endothelial growth factor and basic
fibroblast growth factor.
AB - AIM: To estimate the angiogenic activity in central giant cell granuloma (CGCG)
by immunohistochemical stains for vascular endothelial growth factor (VEGF) and
basic fibroblast growth factor (bFGF). VEGF and bFGF immunoreactivity of the
lesional mononuclear (MC) and giant (GC) cells was also investigated. METHOD: The
study consisted of 41 cases of CGCG. Vascularity was quantified by microvascular
volume (MVV) as determined by point counting. In five cases of CGCG, regions at
the surrounding border, which demonstrated reactive vascular-rich inflammatory
areas, served as control. Immunoreactivity of the MC and GC was assessed as the
percentage of VEGF- and bFGF-positive cells from the total number of the
respective cell type. RESULTS: Within CGCG lesions the extent of angiogenesis was
low; MVV did not exceed 5% for either VEGF (88% of lesions) or bFGF (78% of
lesions). The mean MVV of VEGF- and bFGF-positive blood vessels was 2.9% +/- 2.4%
and 3.46% +/- 2.35%, respectively, significantly lower than in the control areas
(27.5% +/- 7.3% and 28.08% +/- 5.5%, respectively) (P = 0.043). VEGF-positive and
bFGF-positive MC and GC were found in nearly all lesions and in less than half of
the lesions, respectively. CONCLUSION: The low mean MVV of VEGF- and bFGF
positive blood vessels implies low angiogenic activity, which does not support
the designation of CGCG as a true proliferative vascular lesion. MC and GC
immunoreactivity for the angiogenic factors is assumed to play an important role
in the osteoclastogenesis process, thus contributing to additional growth of the
CGCG lesions.
PMID- 17032395
TI - RANKL and cathepsin K in diffuse sclerosing osteomyelitis of the mandible.
AB - BACKGROUND: Diffuse sclerosing osteomyelitis (DSO) of the mandible is
characterized by mixed bone resorption and formation. METHODS:
Immunohistopathology of DSO in the clinically acute and subacute phases was
compared with healthy bone. RESULTS: Receptor activator of nuclear factor kappaB
ligand (RANKL) was found in DSO lesions. When it was used in vitro to stimulate
monocytes, cathepsin K expression was observed in mononuclear prefusion
precursors and in multinuclear giant cells. Similarly, exacerbations of DSO were
characterized by RANKL and induction of cathepsin K in mononuclear precursor
cells, which subsequently seem to differentiate into osteoclasts or foreign body
giant cells. The proportion of bone to soft tissue increased with the duration of
disease. CONCLUSIONS: RANKL-driven osteoclastogenesis and acidic cysteine
endoproteinase cathepsin K seem to play important roles in DSO as osteoclast
mediated bone resorption may represent the primary disease process later followed
by new bone formation.
PMID- 17032396
TI - No evidence of hepatitis C virus infection in Serbian patients with oral
leukoplakia.
AB - BACKGROUND: A review of the literature reveals controversy regarding the
relationship between hepatitis C virus (HCV) infection and oral leukoplakia (OL).
The aim of this study was to determine the frequency of HCV antibodies in
patients with OL and control subjects resident in Serbia. METHODS: In this cross
sectional study 73 consecutive patients with histologically proven OL and 90
control subjects, whose age and gender were matched, were examined for the
presence of serological evidence of chronic hepatic disease, hepatitis B surface
antigen (HBsAg) and anti-HCV seropositivity. RESULTS: None of the patients with
OL or control subjects had antibodies to HCV or HBsAg. All patients with OL and
control subjects had normal liver function. CONCLUSION: The present data indicate
that patients with OL resident in Serbia do not have evidence of HCV or HBV
infection.
PMID- 17032397
TI - Incidental Langerhans cell histiocytosis of the parotid gland resembling marginal
zone B-cell lymphoma: a case report.
AB - Langerhans cell histiocytosis (LCH) manifesting as a parotid gland mass is an
extremely rare clinical presentation. We report a case of LCH involving the
bilateral parotid glands in an 81-year-old Japanese female. Pathologically, the
lesion was characterized by numerous lymphoid follicles, dense lymphoplasmacytoid
infiltrate and cystic dilatation of the parotid gland duct in addition to nodular
and diffuse proliferation of LCs. Moreover, both LCs and small T-lymphocytes
invaded the ductal epithelium forming a lymphoepithelial lesion-like morphology.
The present case indicates that LCHs should be added to the different diagnosis
for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type
involving the salivary glands.
PMID- 17032398
TI - Verrucous carcinoma of the buccal mucosa: histopathological, cytological and DNA
cytometric features.
AB - We describe a patient with an exophytic oral lesion diagnosed as verrucous
carcinoma. The lesion existed without metastases, at least 5 years. Local
excisions led to recurrences and continuous expansion. Scalpel biopsies for
histopathological and polymerase chain reaction examination were obtained from
characteristic regions of the lesion. Brush biopsies for exfoliative cytology
(EC) were taken, in order to screen the mucosal area covered by the lesion. After
Feulgen restaining of the smears, nuclear DNA contents were measured using a TV
image analysis system. An exophytic lesion of the buccal mucosa was diagnosed as
low-grade malignant through histopathology and EC combined with DNA-image
cytometry (peritetraploid DNA-aneuploidy). Due to almost normal microscopic
appearance of the epithelium of verrucous carcinoma, thorough cytological/DNA
cytometric and histological examinations are needed. Brush biopsies of such
neoplastic oral lesions showing DNA-aneuploidy with peritetraploid stemlines
should be used for diagnosis and follow-up examination of these patients.
PMID- 17032399
TI - Ligneous alveolar gingivitis in the absence of plasminogen deficiency.
AB - A case of localized, longstanding, asymptomatic ligneous gingivitis affecting the
crest of the edentulous lower left posterior alveolar ridge (ligneous alveolar
gingivitis) of a middle-aged Caucasian woman is presented. This patient did not
have any associated ophthalmic lesions (ligneous conjunctivitis) and did not have
a plasminogen deficiency.
PMID- 17032400
TI - Seckel syndrome associated with oligodontia, microdontia, enamel hypoplasia,
delayed eruption, and dentin dysmineralization: a new variant?
AB - Seckel syndrome (SCKL) [OMIM Entry 210600] is a rare, autosomal recessive
syndrome, characterized by severe intrauterine and postnatal growth retardation,
microcephaly, mental retardation, and typical facial appearance with beaklike
protrusion of the midface (bird-headed). Associated findings may include limb
anomalies, dislocation of femoral heads, scoliosis, and gastrointestinal
malformation. A 14-year-old boy is presented with brain hypoplasia, pachygyria,
hydrocephaly, enamel hypoplasia and root dysplasia in the temporary dentition,
and oligodontia, severe microdontia, and delayed eruption of the permanent
dentition. The association of SCKL with the above unusual dental findings may
represent a new phenotype.
PMID- 17032401
TI - Genes or environment to determine alcoholic liver disease and non-alcoholic fatty
liver disease.
AB - While the vast majority of heavy drinkers and individuals with obesity, insulin
resistance, and the metabolic syndrome will have steatosis, only a minority will
ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental
risk factors for advanced alcoholic liver disease (ALD) and non-alcoholic fatty
liver disease (NAFLD) seem likely to include factors that influence the severity
of steatosis and oxidative stress, the cytokine milieu, the magnitude of the
immune response, and/or the severity of fibrosis. For ALD, the dose and pattern
of alcohol intake, along with obesity are the most important environmental
factors determining disease risk. For NAFLD, dietary saturated fat and
antioxidant intake and small bowel bacterial overgrowth may play a role. Family
studies and interethnic variations in susceptibility suggest that genetic factors
are important in determining disease risk. For ALD, functional polymorphisms in
the alcohol dehydrogenases and aldehyde dehydrogenase alcohol metabolising genes
play a role in determining susceptibility in Oriental populations. No genetic
associations with advanced NAFLD have been replicated in large studies.
Preliminary data suggest that polymorphisms in the genes encoding microsomal
triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin
receptor, TNF-alpha, transforming growth factor-beta, and angiotensinogen may be
associated with steatohepatitis and/or fibrosis.
PMID- 17032402
TI - How to modulate inflammatory cytokines in liver diseases.
AB - Most acute and chronic liver diseases are characterized by inflammatory processes
with enhanced expression of various pro- and anti-inflammatory cytokines in the
liver. These cytokines are the driving force of many inflammatory liver disorders
often resulting in fibrosis and cirrhosis. Severe alcoholic hepatitis is a
prototypic tumor necrosis factor-alpha (TNF-alpha)-associated disease. This
knowledge has recently led to pilot studies with promising results investigating
specific anti-TNF drugs such as infliximab or etanercept in the treatment of this
disease, although a recently performed controlled French study did show a
potential detrimental effect of this approach. Anti-TNF treatment strategies
might also improve chronic hepatitis C infection as shown by one controlled trial
using etanercept administered subcutaneously for 24 weeks. Furthermore, several
case reports suggest that TNF-alpha neutralization is not harmful to patients
chronically infected with this virus. In contrast, neutralization of TNF-alpha
worsens and might even be associated with fatalities in chronic hepatitis B
infection. Anti-inflammatory cytokines such as interleukin-10 (IL-10) have also
been tried in patients with chronic liver diseases. Whereas IL-10 administered to
patients with chronic hepatitis C virus infection shows indeed anti-inflammatory
effects in the liver, it seems to act as a proviral agent thereby limiting its
clinical utility. Another cytokine with major anti-inflammatory potential is the
adipokine adiponectin, as its administration is beneficial in many experimental
models of liver injury. Interference with cytokine pathways and/or administration
of anti-inflammatory cytokines will be of major interest in the future therapy of
many liver diseases.
PMID- 17032403
TI - Liver involvement in hereditary hemorrhagic telangiectasia: consensus
recommendations.
AB - STUDY PURPOSE: To formulate recommendations about clinical management of liver
involvement in hereditary hemorrhagic telangiectasia (HHT), using a formal
consensus development process. CONSENSUS PROCESS: A nominal group technique was
used. A list of main clinical, diagnostic and therapeutic issues about liver
involvement in HHT was generated by the organizing committee. Panel members then
scored their agreement with each statement; the median score, and standard
deviation for each statement were determined for each of the three successive
panel rounds. These consensus statements formed the basis for recommendations
graded with the strength and quality of supporting evidence. RECOMMENDATION
STATEMENTS: Doppler US is sufficiently accurate and suitable for first-line
imaging of the liver in the general HHT population. Liver biopsy in any patient
with proven or suspected HHT should be avoided. Liver involvement in HHT is
generally asymptomatic; in the minority of patients where it is symptomatic,
morbidity and mortality can be substantial. The prevalence of focal nodular
hyperplasia is much higher in patients with liver involvement by HHT than in the
general population. Invasive therapies for liver involvement by HHT (namely liver
transplantation) should be considered only in patients who have failed to respond
to intensive medical therapy.
PMID- 17032404
TI - Racial and ethnic variations in the epidemiology of intrahepatic
cholangiocarcinoma in the United States.
AB - BACKGROUND/AIMS: Despite the global increase in the incidence of intrahepatic
cholangiocarcinoma, regional variations occur. To assess the potential
contribution of racial/ethnic factors, we assessed the epidemiology of these
cancers in different racial and ethnic groups in the United States. METHODS:
Disease prevalence, mortality and survival rates for different racial and ethnic
groups were obtained from the surveillance, epidemiology and end results survey
database. RESULTS: The age-adjusted prevalence was highest for Hispanics (1.22
per 100 000) and lowest for Blacks (0.3 per 100 000). Age-adjusted mortality
rates were higher for American Indian/Alaska Natives and Asian/Pacific Islanders
compared with other groups. However, mortality rates increased by greater than
3.5% annual for all racial or ethnic groups except for American Indian/Pacific
Islanders in whom mortality rates decreased by 0.2% annually. The increase in
mortality rates was greatest for Hispanic women aged between 40 and 49 years.
Prevalence and survival were significantly higher in Hispanic women in contrast
to gender differences observed in other groups. CONCLUSIONS: Significant racial
and ethnic variations occur in the epidemiology of intrahepatic
cholangiocarcinoma within geographically defined regions in the United States
These may reflect genetic, socioeconomic or cultural predispositions to cancer.
PMID- 17032405
TI - Quantitative assessment of liver fibrosis: a novel automated image analysis
method.
AB - BACKGROUND: Semiquantitative staging of liver fibrosis is a highly subjective
procedure and may lead to an uncertainty in judgment regarding the degree of
severity and hence the progression of the disease. AIM: In this work, we present
an automated quantification system (AQS) for evaluating the degree of severity of
fibrosis in liver biopsies based on Ishak et al.'s classification. Accordingly,
liver fibrosis is classified into six classes depending on its severity and
progression. The described system is of special value in accurately assessing the
prognosis of chronic liver disease. METHODS: In our method, we tried to
approximate the architecture of the fibrosis in the subject sample using texture
features and shape representation of the fibrosis structural expansion with an
overall accuracy of about 98%. RESULTS AND CONCLUSION: The presented AQS is
considered to be a novel approach in the domain of automatic liver fibrosis
quantification. It is a true quantification and intelligent approach that
attempts to utilize the current semiquantitative methods of liver fibrosis
assessment to turn them into real quantitative ones with significant reduction in
variability and subjectivity. We propose that our method can be adopted by a
panel of expert liver pathologists and software to be developed and used on a
wide scale.
PMID- 17032406
TI - Increased expression of Ob-Rb and its relationship with the overexpression of TGF
beta1 and the stage of fibrosis in patients with nonalcoholic steatohepatitis.
AB - AIMS: The main aim of this study was to examine the relationship of the leptin
system in steatosis and nonalcoholic steatohepatitis (NASH). The study also
analysed the pathogenic role of the leptin system in the development of hepatic
fibrosis and its relation with the TGF-beta1 system. MATERIALS AND METHODS: The
study included 90 subjects, 55 with NASH and 35 with simple steatosis. Gene
expression of leptin, leptin receptor and TGF-beta mRNA was analysed by real-time
PCR on liver tissue. Leptin serum levels were determined by RIA. Leptin receptor
expression was also assessed by immunohistochemistry. RESULTS: Increased
expression was found for leptin receptor mRNA (P=0.0016) and its protein (P<0.05)
in patients with NASH, especially those with fibrosis. There was a marked
increase in gene expression of TGF-beta1 in patients with NASH (P=0.0002). A
strong correlation was demonstrated between leptin receptor gene expression and
TGF-beta1 gene expression (P=0.023). No leptin expression was found in the liver
tissue. All patients showed a marked hyperleptinemia, which was closely related
to the anthropometric characteristics analysed and independent of development or
not of NASH. CONCLUSIONS: The results of the study demonstrate for the first time
increased leptin receptor expression in liver tissue and its relationship with
overexpression of TGF-beta1 and the degree of hepatic fibrosis.
PMID- 17032407
TI - Pulmonary blood volume and transit time in cirrhosis: relation to lung function.
AB - BACKGROUND/AIMS: In cirrhosis a systemic vasodilatation leads to an abnormal
distribution of the blood volume with a contracted central blood volume. In
addition, the patients have a ventilation/perfusion imbalance with a low
diffusing capacity. As the size of the pulmonary blood volume (PBV) has not been
determined separately we assessed PBV and pulmonary transit time (PTT) in
relation to lung function in patients with cirrhosis and in controls. METHODS:
Pulmonary and cardiac haemodynamics and transit times were determined by
radionuclide techniques in 22 patients with alcoholic cirrhosis and in 12
controls. The lung function including diffusing capacity for carbon monoxide (DL,
CO) was determined by conventional single breath technique. RESULTS: In the
patients, PTT was shorter, 3.9+/-1.2 vs 5.7+/-1.0 s in the controls, P<0.001, and
the PBV was lower, 362+/-151 vs 587+/-263 ml, in the controls, P<0.005. Both PTT
and PBV were lowest in patients with advanced disease. DL, CO was reduced in the
patients and correlated significantly with PTT (r=0.58, P=0.007) and PBV (r=0.49,
P<0.03). CONCLUSIONS: The results suggest that the reduced PBV contributes to the
reduced effective blood volume in cirrhosis. The relation between PBV and PTT and
the low diffusing capacity suggests the pulmonary vascular compartment as an
important element in the pathophysiology of the lung dysfunction in cirrhosis.
PMID- 17032408
TI - Anemia associated with antiviral therapy in chronic hepatitis C: incidence, risk
factors, and impact on treatment response.
AB - BACKGROUND: One major side effect of combination antiviral therapy is the
development of anemia, which is more severe among the Asian population. We
conducted this large-scaled study to explore the incidence, risk factors, and
impact on treatment response of anemia in chronic hepatitis C patients receiving
combination antiviral therapy. METHODS: Four hundred and sixty-six chronic
hepatitis C patients were treated with interferon-alpha-2b (IFN-alpha-2b) three
or five million units thrice weekly, or pegylated-IFN-alpha-2b 1-1.5 microg/kg
weekly plus ribavirin (1000-1200 mg/day) for 24 weeks. Severe anemia was defined
as hemoglobin concentration <10 g/dl. RESULTS: The mean decrease of hemoglobin
was 3.9+/-1.3 g/dl. Thirty-nine percent of patients had developed severe anemia
during therapy. Stepwise logistic regression analysis revealed that old age (> or
=50 years) (odds ratio [OR]=1.935, P=0.001) and baseline hemoglobin level (> or
=14 g/dl) (OR=2.975, P<0.001) were significantly correlated with maximal
decreases in hemoglobin. Using Cox's regression analysis, pretreatment platelet
counts (<150 000/mm(3)) (OR=1.821, P<0.001), old age (> or =50 years) (OR=1.789,
P=0.001), female gender (OR=1.739, P<0.001), and low body weight (<65 kg)
(OR=1.493, P=0.027) were independent factors contributing to severe anemia. There
was a significant linear correlation between the sustained virological response
(SVR) rate and the time of severe anemia during therapy (r=0.774, P=0.003),
especially among genotype 1 patients (r=0.960, P<0.001). CONCLUSION: Careful
monitoring of hemoglobin level is necessary in patients who are old, female and
have low body weight and platelet counts. Development of severe anemia was
significantly correlated with the SVR.
PMID- 17032409
TI - Noninvasive tests for the prediction of significant hepatic fibrosis in hepatitis
C virus carriers with persistently normal alanine aminotransferases.
AB - BACKGROUND: The diagnostic value of Doppler and various noninvasive indices in
predicting significant hepatic fibrosis in hepatitis C virus (HCV) carriers with
persistently normal alanine aminotransferases (PNALT) is unknown. METHODS:
Seventy-nine treatment-naive HCV carriers with PNALT, who received Doppler
ultrasonography and percutaneous liver biopsies, were enrolled in the study.
Doppler indices, including portal vein velocity (PVV), hepatic arterial resistive
index (HARI), hepatic arterial pulsatility index (HAPI), splenic arterial
resistive index (SARI), and splenic arterial pulsatility index (SAPI), were
compared with known biochemical indices used in HCV carriers with elevated ALT
levels, including aspartate aminotransferase (AST) to platelet ratio index
(APRI), age-platelet index (API), and AST to ALT ratio (AAR), for the diagnostic
accuracy of significant hepatic fibrosis. RESULTS: SAPI was the most
discriminatory index among the Doppler indices (P<0.001). By comparing areas
under the receiver-operating characteristic (AUROC) of SAPI with various
biochemical indices, SAPI was superior to APRI, API, and AAR for predicting
significant fibrosis (> or =F2) (0.862 vs. 0.673, 0.639, 0.504). SAPI set at 0.85
and 1.10 had a sensitivity of 96.7% and 66.7%, a specificity of 44.6% and 96.0%,
a positive predictive value of 41.4% and 87.1%, and an negative predictive value
of 97% and 87.7% in predicting significant fibrosis. CONCLUSIONS: This study
indicates that SAPI is the most useful index among Doppler and biochemical
indices for the detection of significant hepatic fibrosis in HCV carriers with
PNALT levels.
PMID- 17032410
TI - Noninvasive serum markers in the diagnosis of structural liver damage in chronic
hepatitis C virus infection.
AB - AIM: Several noninvasive markers are being used to assess the structural liver
damage in patients with chronic hepatitis C (CHC). We evaluated the capacity of
serum hyaluronic acid (HA), aspartate aminotransferase (AST)/ALT ratio, the AST
to platelet ratio index (APRI) and gamma-glutamyltransferase (GGT) levels to
predict the intensity of hepatic fibrosis in patients with CHC. PATIENTS AND
METHODS: In a total of 206 hepatitis C virus RNA-positive biopsied patients, AST,
ALT, GGT levels, platelet count and serum HA concentration were determined. The
APRI was calculated as the ratio of AST to platelets. RESULTS: HA levels were
best correlated with disease stage (r=-0.694; P<0.001). In the diagnosis of
significant fibrosis (F2-F4), HA levels [AUC=0.879, 95% CI (0.832-0.927)] and
APRI [AUC=0.824 (0.772-0.903)] were the markers with the best diagnostic
accuracy. These parameters also best identified the presence of cirrhosis (F4),
with an AUC of 0.908 (0.868-0.949) for HA and of 0.837 (0.772-0.903) for APRI.
CONCLUSION: Serum HA was the parameter that alone presented the best diagnostic
accuracy in the assessment of hepatic fibrosis in CHC. The APRI showed a better
diagnostic sensitivity than GGT levels or the AST/ALT ratio. Its simple
determination and low cost make this index a valid alternative for the
noninvasive staging of CHC.
PMID- 17032411
TI - Differential expression of toll-like receptor mRNA in treatment non-responders
and sustained virologic responders at baseline in patients with chronic hepatitis
C.
AB - BACKGROUND/AIMS: The contribution of the host immune response to sustained
virologic response is not clear in patients with chronic hepatitis C (CHC). The
aim of this study was to explore the relationship of the toll-like receptor (TLR)
expression with the outcome of antiviral therapy in hepatitis C viral infection.
METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 15 CHC
patients before a 48-week treatment with pegylated interferon (PEG IFN) alpha-2a
and ribavirin. A multiplex semi-quantitative reverse-trancriptase polymerase
chain reaction (RT-PCR) was used to compare the relative abundance of TLR2-9
transcripts. RESULTS: mRNA levels of TLR2, 3 and 6 were significantly higher in
CHC subjects compared with normal controls (n=8). When patients were classified
into non-responders (n=8) and sustained virological responders (n=7) according to
the virological outcome of the treatment, there was a clear difference in
baseline mRNA expression of TLRs and T-helper (Th) 1/2 cytokines. In addition,
the mRNA expression of IFN-gamma and nuclear factor of activated T cells (NFAT),
which is exclusively expressed in activated T cells, was inversely correlated
with that of TLR4, 6 and 9 in non-responders. CONCLUSIONS: TLRs mRNA levels are
differentially expressed in baseline PBMC of chronic HCV-infected subjects with
or without responsiveness to antiviral therapy.
PMID- 17032412
TI - Zinc is a negative regulator of hepatitis C virus RNA replication.
AB - BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is a significant global public
health problem. In clinical studies, zinc has been closely related to the
pathogenesis of chronic hepatitis C. However, the role of zinc in both viral
replication and the expression of viral proteins remains unclear. We aimed to
clarify the effect of zinc on the replication of HCV in vitro. METHODS: We
incubated subgenomic HCV replicon cells (sO) and genome-length HCV RNA
replicating cells (O) treated with several chemicals including trace elements.
Total RNAs were collected and subjected to real-time reverse-transcriptase
polymerase chain reaction in order to examine the level of HCV RNA replication,
and Western blotting was performed to confirm the expression of viral proteins.
RESULTS: Iron salts and interferon-alpha suppressed HCV RNA replication and
protein expression in both sO and O cells. Zinc salts effectively reduced the
viral replication in the genome-length HCV RNA replication system but not in the
subgenomic HCV replicon system. CONCLUSIONS: We demonstrated that zinc may play
an important role as a negative regulator of HCV replication in genome-length HCV
RNA-replicating cells. Zinc supplementation thus appears to offer a novel
approach to the development of future strategies for the treatment of intractable
chronic hepatitis C.
PMID- 17032413
TI - Impact of liver steatosis on the antiviral response in the hepatitis C virus
associated chronic hepatitis.
AB - BACKGROUND/AIM: Liver steatosis (LS) has been variably associated with chronic
hepatitis C (CHC) but whether it affects sustained virological response to
antiviral treatment and by what mechanisms is a question still under debate, at
least for some genotypes. The aim of this work was to assess the frequency of LS,
its relationship with host and viral factors and to what extent it can influence
the response to antiviral combination therapy with pegylated interferon
(INF)+ribavirin in a group of patients with CHC from a single center. PATIENTS:
One hundred and twelve patients with histologically proven CHC were treated with
Peg INF-alpha 2a 180 microg a week subcutaneously for 48 weeks plus ribavirin
1000 or 1200 mg/day, according to the patient's body weight. Steatosis was graded
according to Brunt et al. RESULTS: Forty-six out of 112 patients (41.1%) were
sustained virological responders (SVR). Seventy-two out of 112 (64.3%) presented
with LS at histology; in this group, there were 24 patients (33.3%) with SVR
compared with 22 (55%) of the non-steatosis group (chi(2)=6.5, P<0.02). Variables
associated with the steatosis group were: higher serum levels of AST (P<0.04),
alanine aminotransferase (P<0.02), gamma-GT (P<0.004), genotype 3a (P<0.03) and
severity of histology (staging P<0.05) but at multiple linear regression analysis
only genotype 3a and staging were significantly associated with LS. In the SVR
group, age and body mass index (BMI) were significantly lower (P<0001 and P<0.03,
respectively) compared with non-responders; moreover, genotype 1 was more
frequent in the NR group, while genotype 3 was more frequent in the SVR group. At
histology, grading and staging were also lower in the SVR group. Multiple
logistic regression showed that only the grade of steatosis and genotype 3a were
the variables independently associated with SVR. CONCLUSIONS: This study showed a
frequency of LS on the higher side of the range so far reported in the literature
and confirmed that it negatively influences response to therapy. Genotype1 was
confirmed to be the most frequent type in our area. It is more frequent in
patients with mild-moderate steatosis and seems to condition therapeutic response
negatively, together with BMI and age. In contrast, genotype 3a is more frequent
in patients with severe steatosis, but is a favorable predictor of successful
therapy.
PMID- 17032414
TI - Differential expression genes analyzed by cDNA array in the regulation of rat
hepatic fibrogenesis.
AB - PURPOSE: To analyze the gene expression pattern in rat hepatic fibrogenesis and
further assess the role of some key genes during the pathological process.
METHODS: Hepatic fibrosis was induced by intraperitoneal injection of
dimethylnitrosamine or carbon tetrachloride (CCl(4)) injection subcutaneously in
rats, and identification of the hepatic fibrosis related genes with cDNA
microarray was performed. After some key genes up-regulated during the
development of hepatic fibrosis were screened and confirmed, their effects on the
function of the activated rat hepatic stellate cells (HSC) were assessed using
the small interfering RNA (siRNA) technique. RESULTS: Using an Atlas rat cDNA
array, a number of differentially expressed genes in fibrotic liver tissues were
identified compared with non-diseased control. A total of 15 genes predominantly
associated with the mitogen-activated protein kinase (MAPK) signal transduction
pathway were upregulated in the fibrotic liver. Immunohistochemical study
revealed that the expressions of both extracellular signal-regulated kinases
(ERK) and ribosomal protein S6 kinase (RSK), two of the key genes in the MAPK
pathway, were remarkably induced, which was closely correlated to that of
collagen types I and III during the development of hepatic fibrosis. Transfection
of siRNA targeting ERK1 mRNA (siERK1) into HSC led to a 66% and 72% reduction of
ERK1 mRNA and protein expression, respectively. Furthermore, siERK1 exerted the
inhibition of the proliferation of HSC, accompanied by the induction of HSC
apoptosis and reduction of collagen types I and III. In addition, siERK1
abolished the effect of platelet-derived growth factor-BB on the proliferation of
HSC. CONCLUSIONS: The present study provided strong evidence for the
participation of the MAPK pathway in the pathogenesis of hepatic fibrosis.
Selective targeting of ERK1 inhibitors to HSC might present as a novel strategy
for the treatment of hepatic fibrosis.
PMID- 17032415
TI - Systemic mediators induce fibrogenic effects in normal liver after partial bile
duct ligation.
AB - BACKGROUND/AIMS: Collagen production by activated hepatic stellate cells (HSCs)
is a key event in liver fibrosis, and a number of factors have been characterized
that trigger HSC activation and collagen production. However, it remains unclear
if these factors act locally at the site of injury or also affect HSCs distant to
the site of injury. METHODS: A model of partial bile duct ligation (PBDL) in
which fibrogenesis can be compared between the injured ligated lobe and the non
ligated lobe. RESULTS: After PBDL, HSCs showed an increased expression of
procollagen type I alpha1 mRNA and collagen-reporter gene activity not only in
the ligated lobe, but also in the non-ligated lobe, albeit at a lower level. In
contrast, an increase in the number of desmin- and alpha-smooth muscle actin
positive HSCs, and accumulation of inflammatory cells were observed only in the
ligated lobe. Although transforming growth factor-beta (TGF-beta) mRNA was
increased only in the ligated lobe, Smad2/3 were activated in the ligated and the
non-ligated lobe. These data suggest that the systemic increase in profibrogenic
mediators including TGF-beta induces collagen transcription in the uninjured
liver. CONCLUSION: Systemic profibrogenic mediators from the injury site affect
the residual non-injured liver.
PMID- 17032418
TI - Should children ever be living kidney donors?
PMID- 17032416
TI - Anti-Golgi complex antibodies during pegylated-interferon therapy for hepatitis
C.
AB - BACKGROUND/AIM: Pegylated interferon (Peg-IFN) plus ribavirin is the standard
therapy for hepatitis C. Peg-IFN has several antiviral mechanisms, but its role
in hepatitis C treatment seems to be related to its immunomodulatory effect.
Ribavirin, an antiviral agent, potentiates IFN activity when added to it. Both
drugs are associated with adverse reactions of different magnitudes. Autoimmune
phenomena have been reported with this treatment. In this paper, we describe
cases of ALT/GGT flares during Peg-IFN plus ribavirin treatment, which related to
the appearance of anti-Golgi antibody and disease progress. METHODS: We
investigated three patients with hepatitis C and severe ALT/GGT flares during Peg
IFN and ribavirin treatment coinciding with anti-Golgi complex antibody as the
only marker of autoimmunity. We then reviewed the medical files and tested anti
Golgi antibody in stored sera from 25 patients treated with conventional IFN and
in 14 patients treated with Peg-IFN. RESULTS: The three patients were male, over
45 years of age; all were relapsers and non-responders. Anti-Golgi antibody was
positive during treatment coinciding with ALT/GGT flares but with hepatitis C
virus (HCV)-RNA negativity, disappearing after stopping treatment, with
normalization of ALT/AST levels. One patient had progression of fibrosis from F2
to F3 despite negativity of HCV-RNA. In the last group, only two patients treated
with Peg-IFN experienced ALT/GGT flares but without anti-Golgi antibody
CONCLUSIONS: The presence of anti-Golgi complex antibody could be a marker of a
temporary autoimmune phenomenon and progressive disease.
PMID- 17032417
TI - Redefining reference limits needs more attention to the analytical aspects.
PMID- 17032419
TI - Protocol biopsies should be standard of care for pediatric renal allograft
recipients!
PMID- 17032420
TI - Protocol biopsies should not (yet) be the standard of care in pediatric renal
transplant recipients.
PMID- 17032421
TI - Anticoagulation post-renal transplant: is it indicated?
PMID- 17032422
TI - Evaluation and management of patients with propionic acidemia undergoing liver
transplantation: a comprehensive review.
AB - Propionic acidemia is a rare metabolic disorder that often results in episodic
hyperammonemia, basal ganglia infarction, mental retardation, and cardiomyopathy.
OLT has been used as a treatment for propionic acidemia, but its benefit in
patients with this disease is unclear. The current study was undertaken to
clarify the role of OLT in the management of this disease. The medical
literature, a national registry of US OLT recipients, and a single institution
liver transplant experience were reviewed for cases of OLT for propionic
acidemia. Accumulated cases demonstrate that OLT has resulted in clear evidence
of clinical improvement in several patients, often obviating the need for dietary
restriction or other forms of medical management. OLT appears to halt the decline
in neurocognitive function often associated with propionic acidemia. In total, 12
patients with propionic acidemia have undergone a total of 14 OLTs. A
quantitative analysis of outcomes shows an overall patient survival rate of 72.2%
at one year after OLT. In conclusion, OLT should be considered a treatment option
for patients with propionic acidemia who continue to experience episodes of
hyperammonemia in spite of maximal medical therapy. Early OLT may limit the
development of mental retardation and/or cardiomyopathy.
PMID- 17032423
TI - Orthotopic ovarian transplant--review and three surgical techniques.
AB - Transplantation of organs is a rapidly expanding faculty of medicine. While the
solid organ transplantation has grown by leaps and bounds, ovarian
transplantation is still in its infancy. Although recent interest has been
generated for preservation of fertility in cancer therapy patients, other
indications have emerged. Ovarian dysgenesis with missing normal ovarian
complement and premature ovarian failure has come in the forefront. Three cases
of orthotopic ovarian transplant with different surgical techniques have been
described along with a brief overview.
PMID- 17032424
TI - Outcome after kidney transplantation in children with thrombotic risk factors.
AB - BACKGROUND: According to the data from the North American Pediatric Renal
Transplant Cooperative Study (NAPRTCS), vascular thrombosis accounts for 11.6% of
graft losses in pediatric renal transplantation. In adults, inherited and
acquired thrombophilic risk factors, e.g. factor V Leiden mutation, have been
associated with early graft loss and increased rejection episodes. Data on the
impact of these factors on the outcome of children after renal transplantation
are rare. METHODS/PATIENTS: Sixty-six pediatric patients awaiting renal
transplantation (mean age 10.1 yr) were screened for inherited and acquired risk
factors for hypercoagulable disorders (protein C, S, and antithrombin III
deficiency, antiphospholipid antibodies, factor V Leiden, prothrombin, and MTHFR
mutation) in order to intensify anticoagulation in those with an increased risk
for thrombophilia: intravenous heparin was administered with a partial
prothrombin time (PTT) prolongation of 50 s for 14 days and switched to low
molecular-weight heparin for another 8 wk before aspirin was introduced for the
first year. Patients without hypercoagulable risk factors were treated with
heparin without PTT prolongation for 14 days and switched to aspirin immediately
afterwards. The results on graft survival, incidence of acute rejection episodes,
and long-term renal graft function were analyzed between recipients with and
without hypercoagulable risk factors. RESULTS: Thrombophilic risk factors were
identified in 27.3% of our patients. No thrombosis occurred. One serious bleeding
complication led to a second surgical intervention. The rate of acute rejection
episodes was not increased in patients with and without thrombotic risk factors
after 90 days (16.7 vs. 25%), 1 yr (22.2 vs. 33.3%), and 3 yr (38.9 vs. 41.7%) of
follow-up, respectively (p = n.s.). After a mean follow-up of 3 yr the kidney
function was comparable in both groups, with 63.1 in recipients with and 69.8
mL/min/1.73 m(2) in recipients without hypercoagulable risk (p = n.s.). At latest
follow-up, three graft losses were found not to be attributed to thrombotic risk
factors. INTERPRETATION: Children with thrombophilic risk factors were identified
and treated with an intensified anticoagulation regimen after renal
transplantation. An increased risk for graft failure, acute rejection episodes,
or impaired renal function for pediatric renal transplant recipients with
hypercoagulable status was not found.
PMID- 17032425
TI - Antibodies to 60, 65 and 70 kDa heat shock proteins in pediatric allogeneic stem
cell transplant recipients.
AB - Allogeneic SCT remains the only means of cure for many patients with various
malignant disorders as well as non-malignant diseases. Infection together with
severe aGvHD may result in a significant incidence of transplant-related
morbidity and mortality. Current evidence suggests that hSPS represent major
immunodominant antigens in many pathogens and therefore might play an important
role in the pathogenesis of GvHD. We investigated the levels of total Ig, IgG and
IgM isotype antibodies to rh-hsp60, recombinant Mycobacterium bovis hsp65 and
stress-inducible rh-hsp70 in sera of pediatric patients undergoing SCT by using
ELISA. We studied whether humoral immune responses to hSPS follow transplant
related complications, bacterial and fungal infection. Anti-hsp antibodies were
detected in patients' sera before conditioning, over the course of conditioning
and all the time post-transplant. We found no correlation between anti-hsp
antibodies and the occurrence and severity of GvHD and/or other transplant
related complications like graft failure, hemorrhagic cystitis and capillary
leakage syndrome. However, elevated anti-hsp antibodies involving IgM and IgG
isotypes were found to be associated with bacterial and fungal infection
depending on etiological agents. We demonstrated de novo humoral response to hSPS
in a cohort of patients with actual infection caused by Klebsiella pneumoniae
(anti-hsp60, anti-hsp65 and anti-hsp70), Pseudomonas aeruginosa (anti-hsp60, anti
hsp70) and Aspergillus fumigatus (anti-hsp65). We conclude that anti-hsp
antibodies might be produced after SCT in relation to infection depending on
etiological agents; however, transplant-related complications by themselves had a
little impact.
PMID- 17032426
TI - Five years' experience with thymoglobulin induction in a pediatric renal
transplant population.
AB - Antibody induction therapy is used in the majority of pediatric patients
undergoing renal transplantation. Our center has previously reported short-term
outcomes with TMG as induction therapy. We now present our experience over the
last five yr. Patients received TMG intra- and post-operatively at a dose of 1.5
mg/kg/day. The dose was decreased to 0.75 mg/kg/day or held dependent on the
patient's WBC and platelet counts. Post-transplant immunosuppression also
included corticosteroids, MMF, and either TAC or CSA. Patient and graft survival,
number of acute rejection episodes, creatinine clearance, incidence and type of
infections, and trough levels of calcineurin inhibitor drugs were monitored
during the follow-up period. Thirty-four renal transplants were performed in 33
pediatric patients ranging in age from 1.7 to 17.8 yr. Seventeen rejection
episodes occurred during the time of follow-up with three patients having more
than one episode, but only three episodes occurred within the first year after
transplantation. Three patients had graft loss in the first week after
transplantation from primary non-function (1) or technical failure/thrombosis
(2). Graft losses occurred in seven additional patients during the time of follow
up with the first loss occurring at 17.7 months. Among patients with functional
grafts at one wk after transplant, graft survival at one and three yr was 100%
and 73% respectively. There were no patient deaths. There were no cases of post
transplant lymphoproliferative disease or other malignancy. One patient had
symptomatic CMV disease. TMG is safe and effective as induction therapy in
pediatric renal transplant patients. Late graft loss remains a challenge in the
pediatric patient population, particularly in adolescents.
PMID- 17032427
TI - Left ventricular hypertrophy in pediatric kidney transplant recipients: long-term
follow-up study.
AB - Cross-sectional studies indicate that LVH, known cardiovascular risk factor, is
frequent in pediatric patients post-kidney transplant. We performed a
retrospective longitudinal analysis of echocardiographic data collected in
children and adolescents who received kidney transplant from 1998 to 2003. The
first echo was performed at a median time post-transplant of 14 months in 47
children; a second echo (echo 2) was carried out at a median time of 33 months in
31 and a third echo (echo 3) was performed at a median time of 49 months in 14
children. LVH was defined as LV mass index >/=95th percentile for children. LVH
was present in echo 1 in 25 (54%) subjects. Systolic blood pressure (p = 0.02)
and BMI (p = 0.02) independently predicted the LVH seen in echo1 in multivariate
logistic regression. In 14 subjects with three consecutive echocardiograms LVM
index significantly decreased from echo 1 to echo 2 and from echo 1 to echo3 (p <
0.05), but no significant changes were observed between echo 2 and echo 3. The
overall prevalence of LVH remained unchanged but its severity significantly
decreased during the follow-up. The results of the study suggest that despite
regression of LVM index overtime-pediatric patients post-kidney transplant are at
continuous risk for developing cardiovascular disease.
PMID- 17032428
TI - Rabbit antithymocyte globulin related decrease in platelet count reduced risk of
pediatric renal transplant graft thrombosis.
AB - Graft thrombosis is a serious complication in pediatric renal transplantation. We
assess a potential protective effect for the decrease in platelet count
associated with RATG therapy against pediatric renal transplant graft vascular
thrombosis. Between January 1986 and December 1998, 120 kidney transplants were
performed in 95 pediatric recipients. Patients were divided into two groups.
Group 1 (n = 61), non-RATG group received cyclosporine, azathioprine and
steroids, while group 2 (n = 59), RATG group, received in addition, RATG at day 1
and continued for 4-10 days postoperatively. Platelet count prior to transplant,
median change in absolute platelet count at 1 and 3 days post-transplant was
recorded. Graft thrombosis incidence was examined. Six grafts (5%) developed
thrombosis. All were in group 1 (p = 0.028). Median pretransplant platelet count
(x10(9)/L) in group 1 was 283 vs. 280 in group 2 (p = 0.921). Median decrease in
absolute platelet count (x10(9)/L) from pretransplant levels at one and three
days post-transplant for group 1 and 2 was 18 vs. 83 (p = 0.001) and 39 vs. 105
(p = 0.001), respectively. Graft thrombosis risk factors were similar in both
groups. RATG use was statistically significant (p = 0.044) for reduced risk of
graft thrombosis in multivariate analysis. Patients receiving RATG showed
significant decrease in both platelet count and graft thrombosis incidence. A
role for RATG related effect on platelet count is assumed.
PMID- 17032429
TI - Rapid progression of metastatic osteosarcoma after initiation of a reduced
intensity conditioning regimen with immunosuppressive fludarabine.
AB - Indications for RIST have not been established in patients with solid tumors. In
this study, we performed RIST as immunotherapy in a 13-yr-old girl with
intractable but not progressive osteosarcoma, which originated from the inter
costal region. Carcinomatous pleurisy suddenly developed after the start of a
conditioning regimen that included Flu and BUS. She died of respiratory failure
on day +19 without signs of engraftment. This case suggests that unexpected
acceleration of tumor growth may occur following RIST with immunosuppressive
drugs before the development of a beneficial GVT effect.
PMID- 17032430
TI - Significant morbidity associated with RSV infection in immunosuppressed children
following liver transplantation: case report and discussion regarding need of
routine prophylaxis.
AB - Respiratory syncytial virus (RSV) is an important cause of lower respiratory
tract infection in infants and young children. In immunocompromised children, RSV
infection poses a serious health threat with significantly increased and
prolonged virus shedding and the development of severe respiratory disease. We
report two patients, eight months and 20 months of age, who were admitted with
severe RSV infection two months and 10 months post-transplant respectively. Major
risk factors for severe infection is the degree of immunosuppression and the age
of the patient (<24 months). Based on the significant morbidity associated with
RSV infection in these patients, we recommend randomized trials in larger
pediatric solid organ transplant centers to evaluate the use of palivizumab
prophylaxis is efficacious to prevent morbidity in patients under the age of 24
months, while we emphasize good hygienic practices to prevent RSV nosocomial
infection.
PMID- 17032432
TI - Obstructive jaundice caused by biliary stone formation around the stent after
liver transplantation.
AB - We report an unusual case of obstructive jaundice caused by a biliary stone,
which developed in the stump of a Roux-en-Y hepaticojejunostomy after undergoing
LT. The patient was a 13-yr-old male. At 74 days after birth, a
hepaticojejunostomy (Kasai's procedure) was performed for the treatment of
biliary atresia. He underwent a reduced size deceased donor LT in the left
subphrenic space twice at the age of one and three years in Australia. Eleven
years after his second LT, he developed liver dysfunction and jaundice with a low
grade fever. Computed tomography showed a marked jejunal loop enlargement by a
rugby ball-shaped stone and the bile duct in the graft was thus dilated. A
surgical exploration revealed the jejunal loop to be bent sharply while its stump
side was dilated by stagnated bile including a biliary stone. The stone included
a stent that had been previously used for the hepaticojejunostomy. This case
suggests that a retained stent used for hepaticojejunostomy had thus caused
biliary stone formation because of a combination of various conditions in the
jejunal loop.
PMID- 17032431
TI - Autologous hematopoietic stem cell transplant with melphalan and thiotepa is safe
and feasible in pediatric patients with low normalized glomerular filtration
rate.
AB - Normalized glomerular filtration rate (nGFR) <60 mL/min/1.73 m(2) often precludes
hematopoietic stem cell transplant (HSCT) in pediatric patients. Three patients
with nGFR < 60 mL/min/1.73 m(2) enrolled on an institutional phase I trial of
HSCT preparative therapy for advanced and recurrent solid tumors with escalating
melphalan, ranging from 135 to 180 mg/m(2), thiotepa (600 mg/m(2)), and
vincristine (2 mg/m(2)). An additional patient with low nGFR was treated with the
same preparative therapy. None of the patients developed acute renal failure,
excess toxicities during HSCT or delayed engraftment. These cases demonstrate
that it is feasible and safe to perform HSCT in pediatric patients with low nGFR
using melphalan- and thiotepa-based preparative therapy.
PMID- 17032433
TI - Emerging viral infections in transplantation.
AB - Viral infections are an important complication of transplantation. The
introduction of more potent immunosuppressive agents over the past decade
correlates with an increase in the rate of hospitalizations of transplant
patients with infections. Specifically, viral infections have emerged as a major
source of morbidity and mortality in transplantation. There are several potential
intervention strategies in the face of emerging infections and it is likely that
the approach will differ depending on the virus in question. These include viral
surveillance and pre-emptive therapy, intervention of the transplant community,
and policy change at the level of government, blood bank and organ procurement
organizations. This review focuses on the emergence of the herpesviruses; HHV-6
and HHV-7. In addition, the issue of virus transmission through organ transplant
is addressed with a discussion of West Nile virus and the rabies virus.
PMID- 17032434
TI - Living donor kidney transplantation in pediatric recipients.
AB - Living donor kidney transplantation has increased in frequency in pediatric
patients, accounting for 43% of cases performed between 1987 and 1991, and 52% of
cases performed between 1987 and 2004 in North America. Patient survival has
remained excellent over the years, and is currently over 96% at five years. Graft
survival has improved over the years, and is currently over 95% at one year.
Rejection rates have fallen over the years, and are currently <25% overall, with
selected centers having very low rejection rates. The reasons for these improved
outcomes are likely related to improvements in maintenance immunosuppression,
which include a transition from cyclosporine to tacrolimus-based regimens, and
from azathioprine to mycophenolate mofetil or sirolimus as adjunctive agents.
Steroid withdrawal and steroid avoidance are beginning to be utilized by several
centers, with excellent early outcomes. Finally, while there may be center
effect/learning curve issues involved, the type of donor nephrectomy has recently
been shown to influence early outcomes, particularly in very young recipients.
PMID- 17032435
TI - Should children ever be living kidney donors?
AB - Living kidney donation by minors is an infrequently performed although highly
controversial procedure. This manuscript reports the frequency of this practice
in North America, Europe, Australia and New Zealand. The relevant laws and
professional guidelines are reviewed and the ethical considerations discussed.
PMID- 17032436
TI - Polyoma virus in pediatric renal transplantation.
AB - Renal transplantation is the treatment of choice for children with end-stage
renal disease. Patient survival and allograft survival have improved with better
immunosuppressant regimes to reduce acute allograft rejection but post-transplant
infections have been exacerbated. An emerging problematic virus in the past
decade is the polyoma virus BKV. The features of BKV including the clinical
features in the general and immune compromised population are reviewed and
correlated with pediatric studies in the post-transplant population. These
features are placed in context with lessons learned about BKV in relevant adult
studies.
PMID- 17032437
TI - Pediatric living donor lobar lung transplantation.
AB - Living donor lobar lung transplantation (LDLLT) was developed in order to
mitigate the growing competition for deceased donor (DD) lungs and resultant
increase in waiting list mortality. Because each of the two donor lobes serves as
an entire lung for the recipient, donors who are taller than the recipient are
preferred. Therefore LDLLT is particularly well suited for pediatric recipients
for whom adults serve as donors. Although long-term outcomes after LDLLT reported
by the Organ Procurement and Transplantation Network (OPTN) are worse compared
with DD recipients, overall pediatric outcomes as well as single center reports
from the most experienced programs are more promising. Particularly encouraging
are the findings that bronchiolitis obliterans (OB) is less frequent or less
severe in LDLLT recipients in comparison to DD recipients. Moreover, outcomes may
be improved by careful selection of donors to ensure adequately sized donor lobes
and minimization of infectious risks. Although no donor deaths have been
reported, there is a moderate risk of significant short-term complications. Long
term follow-up has not been reported. The use of LDLLT has decreased in recent
years, and the recent change by the OPTN to an urgency/benefit allocation system
for DD lungs in patients 12 yr and older may further reduce the demand.
Nonetheless, we anticipate that LDLLT will continue to be utilized in select
circumstances, particularly in children under 12 where access to DD organs
remains challenging.
PMID- 17032438
TI - Determination of bacteriocin activity with bioassays carried out on solid and
liquid substrates: assessing the factor "indicator microorganism".
AB - BACKGROUND: Successful application of growth inhibition techniques for
quantitative determination of bacteriocins relies on the sensitivity of the
applied indicator microorganism to the bacteriocin to which is exposed. However,
information on indicator microorganisms' performance and comparisons in
bacteriocin determination with bioassays is almost non-existing in the
literature. The aim of the present work was to evaluate the parameter "indicator
microorganism" in bioassays carried out on solid -agar diffusion assay- and
liquid -turbidometric assay- substrates, applied in the quantification of the
most studied bacteriocin nisin. RESULTS: The performance of characterized
microorganisms of known sources, belonging to the genera of Lactobacillus,
Pediococcus, Micrococcus and Leuconostoc, has been assessed in this work in the
assays of plate agar diffusion and turbidometry. Dose responses and sensitivities
were examined and compared over a range of assay variables in standard
bacteriocin solutions, fermentation broth filtrates and processed food samples.
Measurements on inhibition zones produced on agar plates were made by means of
digital image analysis. The data produced were analyzed statistically using the
ANOVA technique and pairwise comparisons tests. Sensitivity limits and linearity
of responses to bacteriocin varied significantly among different test
microorganisms in both applied methods, the lower sensitivity limits depending on
both the test-microorganism and the applied method. In both methods, however,
only two of the nine tested microorganisms (Lactobacillus curvatus ATCC 51436 and
Pediococcus acidilactici ATCC 25740) were sensitive to very low concentrations of
the bacteriocin and produced a linear-type of response in all kinds of samples
used in this work. In all cases, very low bacteriocin concentrations, e.g. 1
IU/ml nisin, were more accurately determined in the turbidometric assay.
CONCLUSION: The present work shows that in growth inhibition techniques used in
bacteriocin quantification, the choice of the indicator microorganism is
critical. Evaluation of sensitivity levels and type of produced responses showed
that they can vary widely among different test-microorganisms and different
applied methods, indicating that not all microorganisms can be used successfully
as indicators and that measurements of growth inhibition in liquid media produce
more reliable results.
PMID- 17032439
TI - Comparison between Long-Menu and Open-Ended Questions in computerized medical
assessments. A randomized controlled trial.
AB - BACKGROUND: Long-menu questions (LMQs) are viewed as an alternative method for
answering open-ended questions (OEQs) in computerized assessment. So far this
question type and its influence on examination scores have not been studied
sufficiently. However, the increasing use of computerized assessments will also
lead to an increasing use of this question type. Using a summative online key
feature (KF) examination we evaluated whether LMQs can be compared with OEQs in
regard to the level of difficulty, performance and response times. We also
evaluated the content for its suitability for LMQs. METHODS: We randomized 146
fourth year medical students into two groups. For the purpose of this study we
created 7 peer-reviewed KF-cases with a total of 25 questions. All questions had
the same content in both groups, but nine questions had a different answer type.
Group A answered 9 questions with an LM type, group B with an OE type. In
addition to the LM answer, group A could give an OE answer if the appropriate
answer was not included in the list. RESULTS: The average number of correct
answers for LMQs and OEQs showed no significant difference (p = 0.93). Among all
630 LM answers only one correct term (0.32%) was not included in the list of
answers. The response time for LMQs did not significantly differ from that of
OEQs (p = 0.65). CONCLUSION: LMQs and OEQs do not differ significantly. Compared
to standard multiple-choice questions (MCQs), the response time for LMQs and OEQs
is longer. This is probably due to the fact that they require active problem
solving skills and more practice. LMQs correspond more suitable to Short answer
questions (SAQ) then to OEQ and should only be used when the answers can be
clearly phrased, using only a few, precise synonyms.LMQs can decrease cueing
effects and significantly simplify the scoring in computerized assessment.
PMID- 17032440
TI - TreeDyn: towards dynamic graphics and annotations for analyses of trees.
AB - BACKGROUND: Analyses of biomolecules for biodiversity, phylogeny or
structure/function studies often use graphical tree representations. Many
powerful tree editors are now available, but existing tree visualization tools
make little use of meta-information related to the entities under study such as
taxonomic descriptions or gene functions that can hardly be encoded within the
tree itself (if using popular tree formats). Consequently, a tedious manual
analysis and post-processing of the tree graphics are required if one needs to
use external information for displaying or investigating trees. RESULTS: We have
developed TreeDyn, a tool using annotations and dynamic graphical methods for
editing and analyzing multiple trees. The main features of TreeDyn are 1) the
management of multiple windows and multiple trees per window, 2) the export of
graphics to several standard file formats with or without HTML encapsulation and
a new format called TGF, which enables saving and restoring graphical analysis,
3) the projection of texts or symbols facing leaf labels or linked to nodes,
through manual pasting or by using annotation files, 4) the highlight of
graphical elements after querying leaf labels (or annotations) or by selection of
graphical elements and information extraction, 5) the highlight of targeted trees
according to a source tree browsed by the user, 6) powerful scripts for
automating repetitive graphical tasks, 7) a command line interpreter enabling the
use of TreeDyn through CGI scripts for online building of trees, 8) the inclusion
of a library of packages dedicated to specific research fields involving trees.
CONCLUSION: TreeDyn is a tree visualization and annotation tool which includes
tools for tree manipulation and annotation and uses meta-information through
dynamic graphical operators or scripting to help analyses and annotations of
single trees or tree collections.
PMID- 17032441
TI - A graph-search framework for associating gene identifiers with documents.
AB - BACKGROUND: One step in the model organism database curation process is to find,
for each article, the identifier of every gene discussed in the article. We
consider a relaxation of this problem suitable for semi-automated systems, in
which each article is associated with a ranked list of possible gene identifiers,
and experimentally compare methods for solving this geneId ranking problem. In
addition to baseline approaches based on combining named entity recognition (NER)
systems with a "soft dictionary" of gene synonyms, we evaluate a graph-based
method which combines the outputs of multiple NER systems, as well as other
sources of information, and a learning method for reranking the output of the
graph-based method. RESULTS: We show that named entity recognition (NER) systems
with similar F-measure performance can have significantly different performance
when used with a soft dictionary for geneId-ranking. The graph-based approach can
outperform any of its component NER systems, even without learning, and learning
can further improve the performance of the graph-based ranking approach.
CONCLUSION: The utility of a named entity recognition (NER) system for geneId
finding may not be accurately predicted by its entity-level F1 performance, the
most common performance measure. GeneId-ranking systems are best implemented by
combining several NER systems. With appropriate combination methods, usefully
accurate geneId-ranking systems can be constructed based on easily-available
resources, without resorting to problem-specific, engineered components.
PMID- 17032442
TI - Molecular characterisation of Mycobacterium tuberculosis isolates in the First
National Survey of Anti-tuberculosis Drug Resistance from Venezuela.
AB - BACKGROUND: Molecular typing of Mycobacterium tuberculosis strains has become a
valuable tool in the epidemiology of tuberculosis (TB) by allowing detection of
outbreaks, tracking of epidemics, identification of genotypes and transmission
events among patients who would have remained undetected by conventional contact
investigation. This is the first genetic biodiversity study of M. tuberculosis in
Venezuela. Thus, we investigated the genetic patterns of strains isolated in the
first survey of anti-tuberculosis drug-resistance realised as part of the Global
Project of Anti-tuberculosis Drug Resistance Surveillance (WHO/IUATLD). RESULTS:
Clinical isolates (670/873) were genotyped by spoligotyping. The results were
compared with the international spoligotyping database (SpolDB4). Multidrug
resistant (MDR) strains (14/18) were also analysed by IS6110-RFLP assays, and
resistance to isoniazid and rifampicin was characterised. Spoligotyping grouped
82% (548/670) of the strains into 59 clusters. Twenty new spoligotypes (SITs)
specific to Venezuela were identified. Eight new inter-regional clusters were
created. The Beijing genotype was not found. The genetic network shows that the
Latin American and Mediterranean family constitutes the backbone of the genetic
TB population-structure in Venezuela, responsible of >60% of total TB cases
studied. MDR was 0.5% in never treated patients and 13.5% in previously treated
patients. Mutations in rpoB gene and katG genes were detected in 64% and 43% of
the MDR strains, respectively. Two clusters were found to be identical by the
four different analysis methods, presumably representing cases of recent
transmission of MDR tuberculosis. CONCLUSION: This study gives a first overview
of the M. tuberculosis strains circulating in Venezuela during the first survey
of anti-tuberculosis drug-resistance. It may aid in the creation of a national
database that will be a valuable support for further studies.
PMID- 17032443
TI - Dobutamine reverses the vasopressin-associated impairment in cardiac index and
systemic oxygen supply in ovine endotoxemia.
AB - INTRODUCTION: Arginine vasopressin (AVP) is increasingly used to treat sepsis
related vasodilation and to decrease catecholamine requirements. However, AVP
infusion may be associated with a marked decrease in systemic blood flow and
oxygen transport. The purpose of the present study was to evaluate whether
dobutamine may be titrated to reverse the AVP-related decrease in cardiac index
(CI) and systemic oxygen delivery index (DO2I) in an established model of ovine
endotoxemia. METHODS: Twenty-four adult ewes were chronically instrumented to
determine cardiopulmonary hemodynamics and global oxygen transport. All ewes
received a continuous endotoxin infusion that contributed to a hypotensive
hyperdynamic circulation and death of five sheep. After 16 hours of endotoxemia,
the surviving ewes (n = 19; weight 35.6 +/- 1.5 kg (mean +/- SEM)) were
randomized to receive either AVP (0.04 Umin-1) and dobutamine (n = 8) or the
vehicle (normal saline; n = 6) and compared with a third group treated with AVP
infusion alone (n = 5). Dobutamine infusion was started at an initial rate of 2
microg kg-1min-1 and was increased to 5 and 10 microg kg-1 min-1 after 30 and 60
minutes, respectively. RESULTS: AVP infusion increased mean arterial pressure
(MAP) and systemic vascular resistance index at the expense of a markedly
decreased CI (4.1 +/- 0.5 versus 8.2 +/- 0.3 l min-1 m-2), DO2I (577 +/- 68
versus 1,150 +/- 50 ml min-1 m-2) and mixed-venous oxygen saturation (SvO2; 54.5
+/- 1.8% versus 69.4 +/- 1.0%; all p < 0.001 versus control). Dobutamine dose
dependently reversed the decrease in CI (8.8 +/- 0.7 l min-1 m-2 versus 4.4 +/-
0.5 l min-1 m-2), DO2I (1323 +/- 102 versus 633 +/- 61 ml min-1 m-2) and SvO2
(72.2 +/- 1.7% versus 56.5 +/- 2.0%, all p < 0.001 at dobutamine 10 microg kg-1
min-1 versus AVP group) and further increased MAP. CONCLUSION: This study
provides evidence that dobutamine is a useful agent for reversing the AVP
associated impairment in systemic blood flow and global oxygen transport.
PMID- 17032444
TI - The relationship between facial skeletal class and expert-rated interpersonal
skill: an epidemiological survey on young Italian adults.
AB - BACKGROUND: The facial region plays a major role in determining physical
attractiveness, so we assessed the hypothesis that the capability of successfully
managing interpersonal relationships in young adults might be related to the
facial skeletal class. METHODS: 1,014 young subjects applying to the Military
Academy of Pozzuoli, Italy, were enrolled and the cephalometric evaluation was
performed by calculating the angular relationships between skeletal points
localized by the lateral cephalogram of the face, sorting the subjects in three
groups corresponding to each major facial skeletal class. Concurrently, the
subjects were evaluated by a team of psychiatrists administering the MMPI-2 test
followed by a brief colloquium with each candidate, in order to identify those
subjects characterized by low skills for managing interpersonal relationships.
RESULTS: According to the psychiatric evaluation about 20% of the subjects were
considered potentially unable to manage successfully interpersonal relationships
(NS). Males displayed an about two-fold increased risk of being NS. No
differences were shown in the distribution of the NS male subjects among the
three different facial skeletal classes. On the other hand, NS females displayed
a different distribution among the three facial skeletal classes, with a trend of
about two-fold and four-fold, respectively, for those subjects belonging to
classes II and III, respect to those belonging to class I. CONCLUSION: Females
may be more sensitive to physical factors determining beauty, such as the facial
morphology certainly is. This finding appears to be interesting especially when
thinking about possible orthodontic interventions, although further study is
certainly needed to confirm these results.
PMID- 17032445
TI - Foetal and neonatal alloimmune thrombocytopaenia.
AB - Foetal/neonatal alloimmune thrombocytopaenia (NAIT) results from maternal
alloimmunisation against foetal platelet antigens inherited from the father and
different from those present in the mother, and usually presents as a severe
isolated thrombocytopaenia in otherwise healthy newborns. The incidence has been
estimated at 1/800 to 1/1000 live births. NAIT has been considered to be the
platelet counterpart of Rh Haemolytic Disease of the Newborn (RHD). Unlike RHD,
NAIT can occur during a first pregnancy. The spectrum of the disease may range
from sub-clinical moderate thrombocytopaenia to life-threatening bleeding in the
neonatal period. Mildly affected infants may be asymptomatic. In those with
severe thrombocytopaenia, the most common presentations are petechiae, purpura or
cephalohaematoma at birth, associated with major risk of intracranial haemorrhage
(up to 20% of reported cases), which leads to death or neurological sequelae.
Alloimmune thrombocytopaenia is more often unexpected and is usually diagnosed
after birth. Once suspected, the diagnosis is confirmed by demonstration of
maternal antiplatelet alloantibodies directed against a paternal antigen
inherited by the foetus/neonate. Post-natal management involves transfusion of
platelets devoid of this antigen, and should not be delayed by biological
confirmation of the diagnosis (once the diagnosis is suspected), especially in
case of severe thrombocytopaenia. Prompt diagnosis and treatment are essential to
reduce the chances of death and disability due to haemorrhage. Due to the high
rate of recurrence and increased severity of the foetal thrombocytopaenia in
successive pregnancies, antenatal therapy should be offered. However, management
of high-risk pregnancies is still a matter of discussion.
PMID- 17032446
TI - Triglyceride associated polymorphisms of the APOA5 gene have very different
allele frequencies in Pune, India compared to Europeans.
AB - BACKGROUND: The APOA5 gene variants, -1131T>C and S19W, are associated with
altered triglyceride concentrations in studies of subjects of Caucasian and East
Asian descent. There are few studies of these variants in South Asians. We
investigated whether the two APOA5 variants also show similar association with
various lipid parameters in Indian population as in the UK white subjects.
METHODS: We genotyped 557 Indian adults from Pune, India, and 237 UK white adults
for -1131T>C and S19W variants in the APOA5 gene, compared their allelic and
genotype frequency and determined their association with fasting serum
triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate
general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune
Indian subjects for analysis of linkage disequilibrium with the APOA5 variants.
RESULTS: The APOA5 -1131C allele was more prevalent in Indians from Pune (Pune
Indians) compared to UK white subjects (allele frequency 20% vs. 4%, p =
0.00001), whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015).
Patterns of linkage disequilibrium between the two variants were similar between
the two populations and confirmed that they occur on two different haplotypes. In
Pune Indians, the presence of -1131C allele and the 19W allele was associated
with a 19% and 15% increase respectively in triglyceride concentrations although
only -1131C was significant (p = 0.0003). This effect size was similar to that
seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175
Pune Indian subjects showed that this variant is not in appreciable linkage
disequilibrium with the APOA5 -1131T>C variant (r2 = 0.07). CONCLUSION: This is
the first study to look at the role of APOA5 in Asian Indian subjects that reside
in India. The -1131C allele is more prevalent and the 19W allele is less
prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5
variants are associated with triglyceride levels independent of ethnicity and
that this association is similar in magnitude in Asian Indians and Caucasians.
The -1131C allele is present in 36% of the Pune Indian population making it a
powerful marker for looking at the role of elevated triglycerides in important
conditions such as pancreatitis, diabetes and coronary heart disease.
PMID- 17032447
TI - Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in
invasive breast carcinoma: relation to tumor phenotype and clinical outcome.
AB - INTRODUCTION: Our aim was to study the expression pattern of tissue inhibitor of
metalloproteinases (TIMP)-3 protein in invasive breast carcinoma, and its
clinicopathological and prognostic value as well as its relation to markers
indicative of the tumor phenotype. METHODS: Immunohistochemistry was performed on
paraffin-embedded tissue specimens from 173 invasive breast carcinomas to detect
the proteins TIMP-3, estrogen receptor (ER), progesterone receptor, p53, c-erbB
2, topoisomerase IIalpha and Bcl-2. RESULTS: TIMP-3 protein was immunodetected in
the cytoplasm of the malignant cells and the peritumoral stroma, as well as in in
situ carcinoma and normal epithelium. Reduced expression of TIMP-3 protein within
cancer cells was correlated with carcinomas of high nuclear and histological
grade (p = 0.032 and p = 0.015, respectively), and low ER expression (p = 0.053).
Moreover, TIMP-3 immunopositivity was inversely correlated with the expression of
p53 and topoIIalpha proteins (p = 0.002 and p = 0.008, respectively), whereas it
was positively associated with Bcl-2 expression (p = 0.020). Reduced expression
of TIMP-3 protein within cancer cells was found to have an unfavorable impact on
disease-free survival (p = 0.052) in the entirety of the patient population, as
well as in both subgroups of lymph-node-positive and mutant-p53-negative patients
(p = 0.007 and p = 0.037, respectively). Stromal localization of TIMP-3 protein
was found to have no clinicopathological or prognostic value. CONCLUSION: This is
the first immunohistochemical study to show that TIMP-3 protein within cancer
cells is associated with tumor phenotype. Reduced expression of TIMP-3 protein
within cancer cells was found to correlate with an aggressive tumor phenotype,
negatively affecting the disease-free survival of both subgroups of lymph node
positive and mutant-p53-negative patients.
PMID- 17032448
TI - Spatial confidentiality and GIS: re-engineering mortality locations from
published maps about Hurricane Katrina.
AB - BACKGROUND: Geographic Information Systems (GIS) can provide valuable insight
into patterns of human activity. Online spatial display applications, such as
Google Earth, can democratise this information by disseminating it to the general
public. Although this is a generally positive advance for society, there is a
legitimate concern involving the disclosure of confidential information through
spatial display. Although guidelines exist for aggregated data, little has been
written concerning the display of point level information. The concern is that a
map containing points representing cases of cancer or an infectious disease,
could be re-engineered back to identify an actual residence. This risk is
investigated using point mortality locations from Hurricane Katrina re-engineered
from a map published in the Baton Rouge Advocate newspaper, and a field team
validating these residences using search and rescue building markings. RESULTS:
We show that the residence of an individual, visualized as a generalized point
covering approximately one and half city blocks on a map, can be re-engineered
back to identify the actual house location, or at least a close neighbour, even
if the map contains little spatial reference information. The degree of re
engineering success is also shown to depend on the urban characteristic of the
neighborhood. CONCLUSION: The results in this paper suggest a need to re-evaluate
current guidelines for the display of point (address level) data. Examples of
other point maps displaying health data extracted from the academic literature
are presented where a similar re-engineering approach might cause concern with
respect to violating confidentiality. More research is also needed into the role
urban structure plays in the accuracy of re-engineering. We suggest that health
and spatial scientists should be proactive and suggest a series of point level
spatial confidentiality guidelines before governmental decisions are made which
may be reactionary toward the threat of revealing confidential information,
thereby imposing draconian limits on research using a GIS.
PMID- 17032449
TI - Analysis of normal and osteoarthritic canine cartilage mRNA expression by
quantitative polymerase chain reaction.
AB - The molecular basis to mammalian osteoarthritis (OA) is unknown. We hypothesised
that the expression of selected proteases, matrix molecules, and collagens
believed to have a role in the pathogenesis of OA would be changed in naturally
occurring canine OA cartilage when compared to normal articular cartilage.
Quantitative (real-time) reverse transcriptase-polymerase chain reaction assays
were designed measuring the expression of selected matrix molecules (collagens
and small leucine-rich proteoglycans), key mediators of the proteolytic
degradation of articular cartilage (metalloproteinases, cathepsins), and their
inhibitors (tissue inhibitors of matrix metalloproteinases). All data were
normalised using a geometric mean of three housekeeping genes, and the results
subjected to power calculations and corrections for multiple hypothesis testing.
We detected increases in the expression of BGN, COL1A2, COL2A1, COL3A1, COL5A1,
CSPG2, CTSB, CTSD, LUM, MMP13, TIMP1, and TNC in naturally occurring canine OA.
The expression of TIMP2 and TIMP4 was significantly reduced in canine OA
cartilage. The patterns of gene expression change observed in naturally occurring
canine OA were similar to those reported in naturally occurring human OA and
experimental canine OA. We conclude that the expression profiles of matrix
associated molecules in end-stage mammalian OA may be comparable but that the
precise aetiologies of OA affecting specific joints in different species are
presently unknown.
PMID- 17032450
TI - Traditional medicinal plant use in Loja province, Southern Ecuador.
AB - This paper examines the traditional use of medicinal plants in Loja province,
Southern Ecuador.Two hundred fifteen plant species were collected, identified and
their vernacular names and traditional uses recorded. This number of species
indicates that the healers, market vendors and members of the public interviewed
still have a very high knowledge of plants in their surroundings, which can be
seen as a reflection of the knowledge of the population in general. However, the
area represents only an outlier of the larger Northern Peruvian cultural area,
where more than 500 species of plants are used medicinally, indicating that in
Ecuador much of the original plant knowledge has already been lost.Most plant
species registered are only used medicinally, and only a few species have any
other use (construction, fodder, food). The highest number of species is used for
the treatment of "magical" (psychosomatic) ailments (39 species), followed by
respiratory disorders (34), problems of the urinary tract (28), Fever/Malaria
(25), Rheumatism (23) and nervous system problems (20).
PMID- 17032451
TI - The development of the larval nervous system, musculature and ciliary bands of
Pomatoceros lamarckii (Annelida): heterochrony in polychaetes.
AB - BACKGROUND: To understand the evolution of animals it is essential to have taxon
sampling across a representative spread of the animal kingdom. With the recent
rearrangement of most of the Bilateria into three major clades (Ecdysozoa,
Lophotrochozoa and Deuterostomia) it has become clear that the Lophotrochozoa are
relatively poorly represented in our knowledge of animal development, compared to
the Ecdysozoa and Deuterostomia. We aim to contribute towards redressing this
balance with data on the development of the muscular, nervous and ciliary systems
of the annelid Pomatoceros lamarckii (Serpulidae). We compare our data with other
lophotrochozoans. RESULTS: P. lamarckii develops locomotory and feeding
structures that enable it to become a swimming, planktotrophic larva within 24
hours. Formation of the trochophore includes development of a prototroch,
metatroch and neurotroch, development of apical and posterior nervous elements at
similar times, and development of musculature around the ciliary bands and
digestive tract prior to development of any body wall muscles. The adult nervous
and muscular systems are essentially preformed in the late larva. Interestingly,
the muscular systems of the larvae and juvenile worms do not include the circular
muscles of the body wall, which are considered to be plesiomorphic for annelids,
although the possibility that circular muscles develop after these stages cannot
be ruled out at this point. CONCLUSION: A comparison between polychaetes shows
variability in the timing (heterochrony) of development of body wall muscles and
elements of the nervous system. These heterochronies are one route for evolution
of different life history strategies, such as adaptations to feeding
requirements.
PMID- 17032452
TI - Exhaustive assignment of compositional bias reveals universally prevalent biased
regions: analysis of functional associations in human and Drosophila.
AB - BACKGROUND: Compositionally biased (CB) regions are stretches in protein
sequences made from mainly a distinct subset of amino acid residues; such regions
are frequently associated with a structural role in the cell, or with protein
disorder. RESULTS: We derived a procedure for the exhaustive assignment and
classification of CB regions, and have applied it to thirteen metazoan proteomes.
Sequences are initially scanned for the lowest-probability subsequences (LPSs)
for single amino-acid types; subsequently, an exhaustive search for lowest
probability subsequences (LPSs) for multiple residue types is performed
iteratively until convergence, to define CB region boundaries. We analysed >
40,000 CB regions with > 20 million residues; strikingly, nine single-/double-
residue biases are universally abundant, and are consistently highly ranked
across both vertebrates and invertebrates. To home in subpopulations of CB
regions of interest in human and D. melanogaster, we analysed CB region lengths,
conservation, inferred functional categories and predicted protein disorder, and
filtered for coiled coils and protein structures. In particular, we found that
some of the universally abundant CB regions have significant associations to
transcription and nuclear localization in Human and Drosophila, and are also
predicted to be moderately or highly disordered. Focussing on Q-based biased
regions, we found that these regions are typically only well conserved within
mammals (appearing in 60-80% of orthologs), with shorter human transcription
related CB regions being unconserved outside of mammals; they are also
preferentially linked to protein domains such as the homeodomain and
glucocorticoid-receptor DNA-binding domain. In general, only approximately 40-50%
of residues in these human and Drosophila CB regions have predicted protein
disorder. CONCLUSION: This data is of use for the further functional
characterization of genes, and for structural genomics initiatives.
PMID- 17032454
TI - Ciliated hepatic foregut cyst in a patient with renal cell carcinoma.
AB - BACKGROUND: Ciliated hepatic foregut cyst is a rare condition almost always found
incidentally on a computerized tomography scan or at autopsy. Rarely, portal vein
compression can be a presenting finding. The cysts are usually unilocular and
occur with greater frequency in males. There is a predilection for the left lobe.
The cysts average 3 cm in size. CASE PRESENTATION: We present in this case report
a ciliated hepatic foregut cyst found incidentally in the setting of renal
carcinoma. The patient was a man known to have a large renal mass, assumed to be
cancer, and a liver mass suspicious for metastatic disease. This liver mass was
cystic and upon further analysis showed ciliated epithelial lining. We describe
the gross and histological appearance, as well as a brief discussion of ciliated
hepatic foregut cysts. CONCLUSION: We report the first case of a patient with
coexisting renal cell carcinoma and a ciliated hepatic foregut cyst. While this
may represent a coincidental finding, a possibility of a neoplastic or non
neoplastic disorder associated with ciliated hepatic foregut cysts can not be
completely ruled out.
PMID- 17032453
TI - A preliminary study of mercury exposure and blood pressure in the Brazilian
Amazon.
AB - BACKGROUND: Fish is considered protective for coronary heart disease (CHD), but
mercury (Hg) intake from fish may counterbalance beneficial effects. Although
neurotoxic effects of methylmercury (MeHg) are well established, cardiovascular
effects are still debated. The objective of the present study was to evaluate
blood pressure in relation to Hg exposure and fish consumption among a non
indigenous fish-eating population in the Brazilian Amazon. METHODS: The study was
conducted among 251 persons from six communities along the Tapajos River, a major
tributary of the Amazon. Data was obtained for socio-demographic information,
fish consumption, height and weight to determine body mass index (BMI), systolic
and diastolic blood pressure, and Hg concentration in hair samples. RESULTS:
Results showed that overall, systolic and diastolic blood pressure, were
relatively low (mean: 113.9 mmHg +/- 14.6 and 73.7 mmHg +/- 11.0). Blood pressure
was significantly associated with hair total Hg (H-Hg), age, BMI and gender. No
association was observed between fish consumption and blood pressure, although
there were significant inter-community differences. Logistic regression analyses
showed that the Odds Ratio (OR) for elevated systolic blood pressure (> or = 130
mmHg) with H-Hg > or = 10 microg/g was 2.91 [1.26-7.28], taking into account age,
BMI, smoking, gender and community. CONCLUSION: The findings of this preliminary
study add further support for Hg cardiovascular toxicity.
PMID- 17032455
TI - A simple method to combine multiple molecular biomarkers for dichotomous
diagnostic classification.
AB - BACKGROUND: In spite of the recognized diagnostic potential of biomarkers, the
quest for squelching noise and wringing in information from a given set of
biomarkers continues. Here, we suggest a statistical algorithm that--assuming
each molecular biomarker to be a diagnostic test--enriches the diagnostic
performance of an optimized set of independent biomarkers employing established
statistical techniques. We validated the proposed algorithm using several
simulation datasets in addition to four publicly available real datasets that
compared i) subjects having cancer with those without; ii) subjects with two
different cancers; iii) subjects with two different types of one cancer; and iv)
subjects with same cancer resulting in differential time to metastasis. RESULTS:
Our algorithm comprises of three steps: estimating the area under the receiver
operating characteristic curve for each biomarker, identifying a subset of
biomarkers using linear regression and combining the chosen biomarkers using
linear discriminant function analysis. Combining these established statistical
methods that are available in most statistical packages, we observed that the
diagnostic accuracy of our approach was 100%, 99.94%, 96.67% and 93.92% for the
real datasets used in the study. These estimates were comparable to or better
than the ones previously reported using alternative methods. In a synthetic
dataset, we also observed that all the biomarkers chosen by our algorithm were
indeed truly differentially expressed. CONCLUSION: The proposed algorithm can be
used for accurate diagnosis in the setting of dichotomous classification of
disease states.
PMID- 17032456
TI - Comparison of vitrified and unvitrified Eocene woody tissues by TMAH
thermochemolysis - implications for the early stages of the formation of
vitrinite.
AB - Samples of vitrified and unvitrified Eocene woody plant tissues collected from
the Fossil Forest site, Geodetic Hills, Axel Heiberg Island, have been
characterized by TMAH thermochemolysis. All samples are gymnosperm-derived, are
of very low maturity and all share the same post-depositional geologic history.
Differences in the distributions of products observed from vitrified and
unvitrified samples suggest that vitrification of woody tissue is associated with
modification of the lignin C3 side chain, following loss of all or most of the
carbohydrate present in the precursor woody tissues. The key driver of
vitrification appears to be physical compression of the tissue following
biological removal of cellulosic materials.
PMID- 17032457
TI - GOLEM: an interactive graph-based gene-ontology navigation and analysis tool.
AB - BACKGROUND: The Gene Ontology has become an extremely useful tool for the
analysis of genomic data and structuring of biological knowledge. Several
excellent software tools for navigating the gene ontology have been developed.
However, no existing system provides an interactively expandable graph-based view
of the gene ontology hierarchy. Furthermore, most existing tools are web-based or
require an Internet connection, will not load local annotations files, and
provide either analysis or visualization functionality, but not both. RESULTS: To
address the above limitations, we have developed GOLEM (Gene Ontology Local
Exploration Map), a visualization and analysis tool for focused exploration of
the gene ontology graph. GOLEM allows the user to dynamically expand and focus
the local graph structure of the gene ontology hierarchy in the neighborhood of
any chosen term. It also supports rapid analysis of an input list of genes to
find enriched gene ontology terms. The GOLEM application permits the user either
to utilize local gene ontology and annotations files in the absence of an
Internet connection, or to access the most recent ontology and annotation
information from the gene ontology webpage. GOLEM supports global and organism
specific searches by gene ontology term name, gene ontology id and gene name.
CONCLUSION: GOLEM is a useful software tool for biologists interested in
visualizing the local directed acyclic graph structure of the gene ontology
hierarchy and searching for gene ontology terms enriched in genes of interest. It
is freely available both as an application and as an applet at
http://function.princeton.edu/GOLEM.
PMID- 17032458
TI - A case-control study of mastitis: nasal carriage of Staphylococcus aureus.
AB - BACKGROUND: Mastitis is a common problem for breastfeeding women. Researchers
have called for an investigation into the possible role of maternal nasal
carriage of S. aureus in the causation of mastitis in breastfeeding women.
METHODS: The aim of the study was to investigate the role of maternal S. aureus
nasal carriage in mastitis. Other factors such as infant nasal S. aureus
carriage, nipple damage, maternal fatigue and oversupply of milk were also
investigated. A case-control design was used. Women with mastitis (cases, n =
100) were recruited from two maternity hospitals in Melbourne, Australia
(emergency departments, breastfeeding clinics and postnatal wards). Breastfeeding
women without mastitis (controls, n = 99) were recruited from maternal and child
health (community) centres and the rooms of a private obstetrician. Women
completed a questionnaire and nasal specimens were collected from mother and baby
and placed in charcoal transport medium. Women also collected a small sample of
milk in a sterile jar. RESULTS: There was no difference between nasal carriage of
S. aureus in breastfeeding women with mastitis (42/98, 43%) and control women
(45/98, 46%). However, significantly more infants of mothers with mastitis were
nasal carriers of S. aureus (72/88, 82%) than controls (52/93, 56%). The
association was strong (adjusted OR 3.23, 95%CI 1.30, 8.27) after adjustment for
the following confounding factors: income, private health insurance, difficulty
with breastfeeding, nipple damage and tight bra. There was also a strong
association between nipple damage and mastitis (adjusted OR 9.34, 95%CI 2.99,
29.20). CONCLUSION: We found no association between maternal nasal carriage of S.
aureus and mastitis, but nasal carriage in the infant was associated with breast
infections. As in other studies of mastitis, we found a strong association
between nipple damage and mastitis. Prevention of nipple damage is likely to
reduce the incidence of infectious mastitis. Mothers need good advice about
optimal attachment of the baby to the breast and access to skilled help in the
early postpartum days and weeks.
PMID- 17032459
TI - Proximal genomic localization of STAT1 binding and regulated transcriptional
activity.
AB - BACKGROUND: Signal transducer and activator of transcription (STAT) proteins are
key regulators of gene expression in response to the interferon (IFN) family of
anti-viral and anti-microbial cytokines. We have examined the genomic
relationship between STAT1 binding and regulated transcription using multiple
tiling microarray and chromatin immunoprecipitation microarray (ChIP-chip)
experiments from public repositories. RESULTS: In response to IFN-gamma, STAT1
bound proximally to regions of the genome that exhibit regulated transcriptional
activity. This finding was consistent between different tiling microarray
platforms, and between different measures of transcriptional activity, including
differential binding of RNA polymerase II, and differential mRNA transcription.
Re-analysis of tiling microarray data from a recent study of IFN-gamma-induced
STAT1 ChIP-chip and mRNA expression revealed that STAT1 binding is tightly
associated with localized mRNA transcription in response to IFN-gamma. Close
relationships were also apparent between STAT1 binding, STAT2 binding, and mRNA
transcription in response to IFN-alpha. Furthermore, we found that sites of STAT1
binding within the Encyclopedia of DNA Elements (ENCODE) region are precisely
correlated with sites of either enhanced or diminished binding by the RNA
polymerase II complex. CONCLUSION: Together, our results indicate that STAT1
binds proximally to regions of the genome that exhibit regulated transcriptional
activity. This finding establishes a generalized basis for the positioning of
STAT1 binding sites within the genome, and supports a role for STAT1 in the
direct recruitment of the RNA polymerase II complex to the promoters of IFN-gamma
responsive genes.
PMID- 17032461
TI - Secondary penile tumours revisited.
AB - OBJECTIVE: To highlight the salient features of metastatic malignancies involving
the penis, with special reference to the primary tumour sites, metastatic
mechanisms, clinical features, differential diagnosis, treatment and prognosis.
METHODS: A comprehensive search of the literature was performed using MEDLINE and
EMBASE, using the keywords 'penis', 'secondary malignancy', 'metastasis' and
'malignant priapism' to identify reviews and case reports of secondary penile
malignancy. A case of rare clinical presentation of metastatic penile lesion is
presented along with the review of the literature. CONCLUSION: Secondary
malignancy of the penis is a rare clinical entity, despite the rich
vascularisation of this organ. The majority of metastatic lesions take their
origin from the neighbouring genito-urinary organs, mainly prostate and bladder.
These lesions are often associated with disseminated malignancy and hence have a
poor outcome. Nodular or ulcerative lesions involving the corpora cavernosa or
priapism are the main modes of clinical presentation. In most cases, only
palliative or supportive therapy is indicated.
PMID- 17032462
TI - Qualitative and quantitative characteristics of the extracellular DNA delivered
to the nucleus of a living cell.
AB - BACKGROUND: The blood plasma and other intertissue fluids usually contain a
certain amount of DNA, getting there due to a natural cell death in the organism.
Cells of this organism can capture the extracellular DNA, whereupon it is
delivered to various cell compartments. It is hypothesized that the extracellular
DNA is involved in the transfer of genetic information and its fixation in the
genome of recipient cell. RESULTS: The existence of an active flow of
extracellular DNA into the cell is demonstrated using human breast adenocarcinoma
(MCF-7) cells as a recipient culture. The qualitative state of the DNA fragments
delivered to the main cell compartments (cytoplasm and interchromosomal fraction)
was assessed. The extracellular DNA delivered to the cell is characterized
quantitatively. CONCLUSION: It is demonstrated that the extracellular DNA
fragments in several minutes reach the nuclear space, where they are processed so
that their linear size increases from about 500 bp to 10,000 bp. The amount of
free extracellular DNA fragments simultaneously present in the nuclear space may
reach up to 2% of the haploid genome. Using individual DNA fragments with a known
molecular weight and sequence as an extracellular DNA, it is found that these
fragments degrade instantly in the culture liquid in the absence of a competitor
DNA and are delivered into the cell as degradants. When adding a sufficient
amount of competitor DNA, the initial undegraded molecules of the DNA fragments
with the known molecular weight and sequence are detectable both in the cytoplasm
and nuclear space only at the zero point of experiments. The labeled precursor
alpha-dNTP*, added to culture medium, was undetectable inside the cell in all the
experiments.
PMID- 17032463
TI - Host-virus interaction: a new role for microRNAs.
AB - MicroRNAs (miRNAs) are a new class of 18-23 nucleotide long non-coding RNAs that
play critical roles in a wide spectrum of biological processes. Recent reports
also throw light into the role of microRNAs as critical effectors in the
intricate host-pathogen interaction networks. Evidence suggests that both virus
and hosts encode microRNAs. The exclusive dependence of viruses on the host
cellular machinery for their propagation and survival also make them highly
susceptible to the vagaries of the cellular environment like small RNA mediated
interference. It also gives the virus an opportunity to fight and/or modulate the
host to suite its needs. Thus the range of interactions possible through miRNA
mRNA cross-talk at the host-pathogen interface is large. These interactions can
be further fine-tuned in the host by changes in gene expression, mutations and
polymorphisms. In the pathogen, the high rate of mutations adds to the complexity
of the interaction network. Though evidence regarding microRNA mediated cross
talk in viral infections is just emerging, it offers an immense opportunity not
only to understand the intricacies of host-pathogen interactions, and possible
explanations to viral tropism, latency and oncogenesis, but also to develop novel
biomarkers and therapeutics.
PMID- 17032464
TI - Recent advances in the bcr-abl negative chronic myeloproliferative diseases.
AB - The chronic myeloproliferative disorders are clonal hematopoietic stem cell
disorders of unknown etiology. In one of these (chronic myeloid leukemia), there
is an associated pathognomonic chromosomal abnormality known as the Philadelphia
chromosome. This leads to constitutive tyrosine kinase activity which is
responsible for the disease and is used as a target for effective therapy. This
review concentrates on the search in the other conditions (polycythemia vera,
essential thrombocythemia and idiopathic mylofibrosis) for a similar biological
marker with therapeutic potential. There is no obvious chromosomal marker in
these conditions and yet evidence of clonality can be obtained in females by the
use of X-inactivation patterns. PRV-1mRNA over expression, raised vitamin B12
levels and raised neutrophil alkaline phosphatase scores are evidence that cells
in these conditions have received excessive signals for proliferation, maturation
and reduced apoptosis. The ability of erythroid colonies to grow spontaneously
without added external erythropoietin in some cases, provided a useful marker and
a clue to this abnormal signaling. In the past year several important discoveries
have been made which go a long way in elucidating the involved pathways. The
recently discovered JAK2 V617F mutation which occurs in the majority of cases of
polycythemia vera and in about half of the cases with the two other conditions,
enables constitutive tyrosine kinase activity without the need for ligand binding
to hematopoietic receptors. This mutation has become the biological marker for
these conditions and has spurred the development of a specific therapy to
neutralize its effects. The realization that inherited mutations in the
thrombopoietin receptor (c-Mpl) can cause a phenotype of thrombocytosis such as
in Mpl Baltimore (K39N) and in a Japanese family with S505A, has prompted the
search for acquired mutations in this receptor in chronic myeloproliferative
disease. Recently, two mutations have been found; W515L and W515K. These
mutations have been evident in patients with essential thrombocythemia and
idiopathic myelofibrosis but not in polycythemia vera. They presumably act by
causing constitutional, activating conformational changes in the receptor. The
discovery of JAK2 and Mpl mutations is leading to rapid advancements in
understanding the pathophysiology and in the treatment of these diseases.
PMID- 17032465
TI - Extent and structure of health insurance expenditures for complementary and
alternative medicine in Swiss primary care.
AB - BACKGROUND: The study is part of a nationwide evaluation of complementary and
alternative medicine (CAM) in primary care in Switzerland. The goal was to
evaluate the extent and structure of basic health insurance expenditures for
complementary and alternative medicine in Swiss primary care. METHODS: The study
was designed as a cross-sectional evaluation of Swiss primary care providers and
included 262 certified CAM physicians, 151 noncertified CAM physicians and 172
conventional physicians. The study was based on data from a mailed questionnaire
and on reimbursement information obtained from health insurers. It was therefore
purely observational, without interference into diagnostic and therapeutic
procedures applied or prescribed by physicians. Main outcome measures included
average reimbursed costs per patient, structured into consultation- and
medication-related costs, and referred costs. RESULTS: Total average reimbursed
cost per patient did not differ between CAM physicians and conventional
practitioners, but considerable differences were observed in cost structure. The
proportions of reimbursed costs for consultation time were 56% for certified CAM,
41% for noncertified CAM physicians and 40% for conventional physicians;
medication costs--including expenditures for prescriptions and directly dispensed
drugs--respectively accounted for 35%, 18%, and 51% of costs. CONCLUSION: The
results indicate no significant difference for overall treatment cost per patient
between CAM and COM primary care in Switzerland. However, CAM physicians treat
lower numbers of patients and a more cost-favourable patient population than
conventional physicians. Differences in cost structure reflect more patient
centred and individualized treatment modalities of CAM physicians.
PMID- 17032466
TI - Retinitis pigmentosa.
AB - Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of
photoreceptors and characterized by retinal pigment deposits visible on fundus
examination. Prevalence of non syndromic RP is approximately 1/4,000. The most
common form of RP is a rod-cone dystrophy, in which the first symptom is night
blindness, followed by the progressive loss in the peripheral visual field in
daylight, and eventually leading to blindness after several decades. Some extreme
cases may have a rapid evolution over two decades or a slow progression that
never leads to blindness. In some cases, the clinical presentation is a cone-rod
dystrophy, in which the decrease in visual acuity predominates over the visual
field loss. RP is usually non syndromic but there are also many syndromic forms,
the most frequent being Usher syndrome. To date, 45 causative genes/loci have
been identified in non syndromic RP (for the autosomal dominant, autosomal
recessive, X-linked, and digenic forms). Clinical diagnosis is based on the
presence of night blindness and peripheral visual field defects, lesions in the
fundus, hypovolted electroretinogram traces, and progressive worsening of these
signs. Molecular diagnosis can be made for some genes, but is not usually
performed due to the tremendous genetic heterogeneity of the disease. Genetic
counseling is always advised. Currently, there is no therapy that stops the
evolution of the disease or restores the vision, so the visual prognosis is poor.
The therapeutic approach is restricted to slowing down the degenerative process
by sunlight protection and vitaminotherapy, treating the complications (cataract
and macular edema), and helping patients to cope with the social and
psychological impact of blindness. However, new therapeutic strategies are
emerging from intensive research (gene therapy, neuroprotection, retinal
prosthesis).
PMID- 17032460
TI - Analysis of the dermatophyte Trichophyton rubrum expressed sequence tags.
AB - BACKGROUND: Dermatophytes are the primary causative agent of dermatophytoses, a
disease that affects billions of individuals worldwide. Trichophyton rubrum is
the most common of the superficial fungi. Although T. rubrum is a recognized
pathogen for humans, little is known about how its transcriptional pattern is
related to development of the fungus and establishment of disease. It is
therefore necessary to identify genes whose expression is relevant to growth,
metabolism and virulence of T. rubrum. RESULTS: We generated 10 cDNA libraries
covering nearly the entire growth phase and used them to isolate 11,085 unique
expressed sequence tags (ESTs), including 3,816 contigs and 7,269 singletons.
Comparisons with the GenBank non-redundant (NR) protein database revealed
putative functions or matched homologs from other organisms for 7,764 (70%) of
the ESTs. The remaining 3,321 (30%) of ESTs were only weakly similar or not
similar to known sequences, suggesting that these ESTs represent novel genes.
CONCLUSION: The present data provide a comprehensive view of fungal physiological
processes including metabolism, sexual and asexual growth cycles, signal
transduction and pathogenic mechanisms.
PMID- 17032468
TI - Anthelmintic action of plant cysteine proteinases against the rodent stomach
nematode, Protospirura muricola, in vitro and in vivo.
AB - Cysteine proteinases from the fruit and latex of plants, including papaya,
pineapple and fig, were previously shown to have a rapid detrimental effect, in
vitro, against the rodent gastrointestinal nematodes, Heligmosomoides polygyrus
(which is found in the anterior small intestine) and Trichuris muris (which
resides in the caecum). Proteinases in the crude latex of papaya also showed
anthelmintic efficacy against both nematodes in vivo. In this paper, we describe
the in vitro and in vivo effects of these plant extracts against the rodent
nematode, Protospirura muricola, which is found in the stomach. As in earlier
work, all the plant cysteine proteinases examined, with the exception of
actinidain from the juice of kiwi fruit, caused rapid loss of motility and
digestion of the cuticle, leading to death of the nematode in vitro. In vivo, in
contrast to the efficacy against H. polygyrus and T. muris, papaya latex only
showed efficacy against P. muricola adult female worms when the stomach acidity
had been neutralized prior to administration of papaya latex. Therefore,
collectively, our studies have demonstrated that, with the appropriate
formulation, plant cysteine proteinases have efficacy against nematodes residing
throughout the rodent gastrointestinal tract.
PMID- 17032467
TI - Domestic dogs and cats as sources of Trypanosoma cruzi infection in rural
northwestern Argentina.
AB - The reservoir capacity of domestic cats and dogs for Trypanosoma cruzi infection
and the host-feeding patterns of domestic Triatoma infestans were assessed
longitudinally in 2 infested rural villages in north-western Argentina. A total
of 86 dogs and 38 cats was repeatedly examined for T. cruzi infection by serology
and/or xenodiagnosis. The composite prevalence of infection in dogs (60%), but
not in cats, increased significantly with age and with the domiciliary density of
infected T. infestans. Dogs and cats had similarly high forces of infection,
prevalence of infectious hosts (41-42%), and infectiousness to bugs at a wide
range of infected bug densities. The infectiousness to bugs of seropositive dogs
declined significantly with increasing dog age and was highly aggregated.
Individual dog infectiousness to bugs was significantly autocorrelated over time.
Domestic T. infestans fed on dogs showed higher infection prevalence (49%) than
those fed on cats (39%), humans (38%) or chickens (29%) among 1085 bugs examined.
The basic reproduction number of T. cruzi in dogs was at least 8.2. Both cats and
dogs are epidemiologically important sources of infection for bugs and
householders, dogs nearly 3 times more than cats.
PMID- 17032469
TI - The use of chicory for parasite control in organic ewes and their lambs.
AB - The aim of the present study was to investigate the potential benefits of grazing
lactating ewes and their lambs on chicory (Cichorium intybus). Fifty-six
certified organic twin-rearing ewes were either drenched with an anthelmintic or
not, within 2 days after parturition and were grazed upon either grass/clover or
chicory pastures. Around 12 weeks after parturition a subset of 12 lambs per
treatment was slaughtered for worm number and parasite species determination. The
faecal egg counts of lambs from undrenched ewes grazing on chicory were
significantly lower than those of lambs from undrenched ewes grazing on grass.
Lambs grazing on chicory had similar abomasal worm counts as those grazing on
grass at 12 weeks of age; the predominant species was Teladorsagia circumcincta.
There was no difference between the intestinal worm counts in lambs grazing on
grass or chicory, with Trichostrongylus vitrinus being the predominant species.
Liveweight gains over the 126-day experimental period were significantly higher
in lambs from drenched than those from undrenched ewes. Lambs from undrenched
ewes grazing on chicory had higher liveweight gains compared to those from
undrenched ewes grazing on grass. Although chicory grazing did not affect ewe
nematode egg excretion, it resulted in lower egg counts in lambs and improved
their liveweight gains to the same level as those deriving from drenched ewes.
PMID- 17032470
TI - Proteomic analysis of Entamoeba histolytica.
AB - In this study, the proteome of axenically grown Entamoeba histolytica parasites
was explored by two-dimensional gel electrophoresis (2-DE), employing a practical
and effective procedure for the solubilization of E. histolytica proteins.
Approximately 900 protein species in the pH range between 4 and 7 were detected
by Coomassie Blue staining. Ninety-five spots were excised, trypsinated and
subjected to mass spectrometry. The resultant data from peptide mass fingerprints
were compared with those available in the E. histolytica genome and the (non
redundant) National Center for Biotechnology Information (NCBI) databases for the
identification and categorization of proteins. Sixty-three of the proteins
identified were predicted to relate to the cytoskeleton, surface, glycolysis,
RNA/DNA metabolism, the ubiquitin-proteasome system, vesicular trafficking and
signal transduction. The present study demonstrates, for the first time, that
corresponding genes are indeed expressed in E. histolytica and provides a
foundation for further proteomic studies of this parasite.
PMID- 17032471
TI - Antiparasitic effect of calcium and magnesium ion-free buffer treatments against
a common monogenean Neobenedenia girellae.
AB - This study investigated a new effective method for controlling the capsalid
monogenean Neobenedenia girellae. We examined in vitro and in vivo the effect on
the percentage survival of N. girellae in buffers containing different metallic
ions. Decreased survival was observed in buffer solutions lacking two ions. In
particular, the percentage survival of N. girellae was significantly decreased
after 10 min exposure to buffer containing neither Ca(2+) nor Mg(2+).
Transmission electron microscopic observations showed that treatment with this
buffer disrupted intercellular junctions. This significant effect on percentage
survival of N. girellae using Ca(2+)/Mg(2+)-free buffer was confirmed in an in
vivo assay. Ca(2+)/Mg(2+)-free buffer had no effect on the condition of the host,
spotted halibut Verasper variegates (Pleuronectidae). These results suggest that
treatment with Ca(2+)/Mg(2+)-free buffer is a new effective control method, which
could replace existing control methods.
PMID- 17032472
TI - The effect of inulin on new and on patent infections of Trichuris suis in growing
pigs.
AB - The objective of this experiment was to investigate the potential influence of
inulin on the establishment of new and patent infections of Trichuris suis in
growing pigs. Two experimental diets were formulated based on barley flour with
either added insoluble fibre from oat husk (Diet 1) or a pure inulin (16%)
supplementation (Diet 2). Twenty-eight 10-week-old pigs were divided randomly
into 4 groups (Groups 1-4) each of 7 pigs. After 3 weeks adaptation to the
experimental diets all pigs were infected with a single dose of 2000 infective T.
suis eggs. Group 1 was fed Diet 1 until 7 weeks post-infection (p.i.) and Group 3
until 9 weeks p.i., Group 2 was fed Diet 2 until 7 weeks p.i., Group 4 was fed
Diet 1 until week 7 p.i. and was switched-over from Diet 1 to Diet 2 until week 9
p.i. Seven weeks p.i. pigs in Groups 1 and 2 were slaughtered, and pigs in Groups
3 and 4 were slaughtered at 9 weeks p.i. Trichuris suis worm burdens were
determined for all pigs. Inulin-fed pigs (Group 2) exhibited an 87% reduction in
EPG, compared to the pigs on standard diet (Group 1) (P < 0.0001). The number of
worms recovered at week 7 p.i. from pigs on the inulin diet (Group 2) was
significantly reduced by 71%, compared to the pigs on standard diet (Group 1) (P
< 0.01). At week 9, worm recovery in pigs on the inulin diet switch protocol
(Group 4) was reduced by 47% compared to the control pigs in Group 3 (P < 0.01).
Further, the inulin-fed pigs exhibited a significant reduction in female worm
fecundity and worm large intestine location was more distal compared to those
from pigs on standard diet. These results demonstrate that inclusion of the
highly degradable fructose polymer inulin in the diet leads to significant
reductions in T. suis establishment, egg excretion, and female worm fecundity and
can be used as a treatment for patent infections.
PMID- 17032473
TI - Composition and diversity patterns in metazoan parasite communities and
anthropogenic disturbance in stream ecosystems.
AB - The composition and diversity of metazoan parasite communities in naturally
depauperate ecosystems are rarely studied. This study describes the composition
of helminth endoparasite communities infecting fish that are part of naturally
acidic stream ecosystems in the coastal-plains region of the State of New Jersey
(USA) known as the Pinelands, and compares the diversity of parasites between six
streams that differ in anthropogenic disturbance. A total of 514 fish were
examined representing 6 species native but restricted to the Pinelands region, 5
species native and widespread throughout the region and State, and 6 species
introduced to the Pinelands and State. Fish (prevalence: 78%) were infected with
18 helminth endoparasite species. In most streams, prevalence of infection, mean
abundance, and total number of individuals for the 5 most common parasites were
higher in pirate perch, a native fish species. The diversity of helminth
endoparasite communities measured as species richness and Shannon index was
higher in degraded streams, and especially in native or introduced fish at these
sites. Parasite diversity was positively correlated with anthropogenic
disturbance, which was measured by water pH, water conductance, and the
proportion of agricultural and developed land surrounding streams. Helminth
community composition included parasites intimately tied to trophic interactions
in food webs, and disturbance to these ecosystems results in changes to these
communities. Understanding structure and function of animal communities from
these naturally depauperate ecosystems is important before continued
anthropogenic changes result in the extirpation or extinction of their unique
fauna.
PMID- 17032474
TI - Evidence of an altered protective effect of metallothioneins after cadmium
exposure in the digenean parasite-infected cockle (Cerastoderma edule).
AB - The aim of the present study was to analyse the relation between parasitism and
subsequent metallothioneins (MT) in the case of metal contamination. Experimental
exposure of parasitized and unparasitized cockles (Cerastoderma edule) to cadmium
(Cd) was performed, with the cockle as first or second intermediate host of 2
digenean species. After 7 days of Cd exposure in microcosms, cockles infected as
first intermediate host by Labratrema minimus exhibited metal concentrations in
tissues double that in uninfected cockles. Jointly, MT concentrations of
parasitized cockles were not modified in comparison with uninfected individuals
in which concentrations were increased 4.3-fold compared with controls. In
cockles experimentally infected as the second intermediate host by Himasthla
elongata, cadmium concentrations significantly increased again in parasitized
cockles compared with uninfected individuals in contaminated conditions.
Simultaneously, MT concentrations in healthy cockles increased, whereas they
significantly decreased in parasitized individuals. Therefore, the presence of
digenean parasites in Cd-exposed cockles leads to a maintenance or a decrease in
MT concentrations compared with healthy individuals, whereas Cd accumulation in
tissues is significantly increased. These experiments indicate a significant
alteration of the protective effect of metallothioneins towards metals which
could consequently enhance cockle vulnerability. Moreover, these results
highlight the limit of the use of MT as a biomarker of metal pollution in field
monitoring if parasitism is not taken into account.
PMID- 17032475
TI - Mitochondrial genomes of parasitic arthropods: implications for studies of
population genetics and evolution.
AB - Over 39000 species of arthropods parasitize humans, domestic animals and
wildlife. Despite their medical, veterinary and economic importance, most aspects
of the population genetics and evolution of the vast majority of parasitic
arthropods are poorly understood. Mitochondrial genomes are a rich source of
markers for studies of population genetics and evolution. These markers include
(1) nucleotide sequences of each of the 37 mitochondrial genes and non-coding
regions; (2) concatenated nucleotide sequences of 2 or more genes; and (3)
genomic features, such as gene duplications, gene rearrangements, and changes in
gene content and secondary structures of RNAs. To date, the mitochondrial genomes
of over 700 species of multi-cellular animals have been sequenced entirely,
however, only 24 of these species are parasitic arthropods. Of the mitochondrial
genome markers, only the nucleotide sequences of 4 mitochondrial genes, cox1,
cob, rrnS and rrnL, have been well explored in population genetic and
evolutionary studies of parasitic arthropods whereas the sequences of the other
33 genes, and various genomic features have not. We review current knowledge of
the mitochondrial genomes of parasitic arthropods, summarize applications of
mitochondrial genes and genomic features in population genetic and evolutionary
studies, and highlight prospects for future research.
PMID- 17032476
TI - Vector seasonality, host infection dynamics and fitness of pathogens transmitted
by the tick Ixodes scapularis.
AB - Fitness of tick-borne pathogens may be determined by the degree to which their
infection dynamics in vertebrate hosts permits transmission cycles if infective
and uninfected tick stages are active at different times of the year. To
investigate this hypothesis we developed a simulation model that integrates the
transmission pattern imposed by seasonally asynchronous nymphal and larval Ixodes
scapularis ticks in northeastern North America, with a model of infection in
white-footed mice (Peromyscus leucopus) reservoir hosts, using the bacteria
Borrelia burgdorferi and Anaplasma phagocytophilum as examples. In simulations,
survival of microparasites, their sensitivity to reduced rodent and tick
abundance, and to 'dilution' by a reservoir-incompetent host depended on traits
that allowed (i) highly efficient transmission from acutely-infected hosts, (ii)
long-lived acute or 'carrier' host infections, and/or (iii) transmission amongst
co-feeding ticks. Minimum values for transmission efficiency to ticks, and
duration of host infectivity, necessary for microparasite persistence, were
always higher when nymphal and larval ticks were seasonally asynchronous than
when these instars were synchronous. Thus, traits influencing duration of host
infectivity, transmission efficiency to ticks and co-feeding transmission are
likely to be dominant determinants of fitness in I. scapularis-borne
microparasites in northeastern North America due to abiotic forcings influencing
I. scapularis seasonality.
PMID- 17032477
TI - Differential N-glycan- and protein-directed immune responses in Dictyocaulus
viviparus-infected and vaccinated calves.
AB - Calves with naturally acquired Dictyocaulus viviparus infection mount an
effective immune response. In the search for protection-inducing antigens, we
found that several D. viviparus third-stage larval (L3) and adult ES products
carry N-glycans. Deglycosylation of the worm antigens using PNGase F resulted in
reduced IgA, IgE, IgG1 and IgG2 (but not IgM) reactivities in sera of primary
infected animals, suggesting that the carbohydrate moieties contained
immunodominant epitopes. Challenge infection resulted in increased specific serum
antibody levels against ES and L3 in the re-infected and challenge control
groups. Testing of sera by enzyme-linked immunosorbent assay (ELISA) demonstrated
a significant increase in IgG1 and IgE (but not IgA or IgG2) reactivity against
the deglycosylated antigens in the re-infected group compared with the challenge
control group. Sera from calves vaccinated with irradiated larvae showed a strong
anti-N-glycan response, but no booster response against the protein backbone
after challenge infection, consistent with the absence of a memory response.
Together, our results suggest that D. viviparus proteins carry immunodominant N
glycan moieties that elicit a strong but short-lived immune response during
infection and after vaccination, whereas the protein backbones effectively induce
a memory response which results in a long-lasting, potentially protective immune
response in re-infected, but not in vaccinated calves.
PMID- 17032478
TI - Evaluation of an indirect fluorescence immunoassay for the detection of serum
antibodies against Babesia divergens in humans.
AB - Since an indirect fluorescence immunoassay (IFA) for the detection of specific
antibodies against Babesia divergens in human sera is not commercially available,
an in-house prepared B. divergens IFA for the examination of bovine sera was
established for serological studies in humans. To determine whether the described
IFA is appropriate for such studies, 2 B. divergens antigens (of human or bovine
origin) were tested using serum samples obtained from febrile human patients with
a history of 'tick bite'. Sera from other species of animals infected with B.
divergens, Babesia EU1, B. microti or B. canis were also included for comparative
purposes. All serum samples were also tested using a commercially available IFA
for the detection of antibodies against B. microti, and the results compared with
those obtained using blood smear and molecular techniques. This study showed that
the evaluation and standardization of a B. divergens IFA for testing human sera
is critical and that different B. divergens antigens provide different end-point
titres of antibodies, leading to false negative or positive results. Serological
cross-reactivity between B. divergens and Babesia EU1 needs to be taken into
account when interpreting IFA results.
PMID- 17032479
TI - The NcGRA7 gene encodes the immunodominant 17 kDa antigen of Neospora caninum.
AB - A Neospora caninum 17-19 kDa antigenic protein fraction (p17) in one-dimensional
polyacrylamide gel electrophoresis (SDS-PAGE) is the immunodominant antigen
recognized by sera from bovines naturally infected by N. caninum. To identify the
proteins making up the p17 fraction, we screened a new N. caninum tachyzoite cDNA
library with an affinity-purified antibody against p17 (APA17). We isolated
several cDNA clones with 100% sequence identity to the NcGRA7 gene. This
previously described gene encodes a dense granule protein with an apparent
molecular mass of 33 kDa. A second line of evidence emerged through a combined
proteomic approach associating two-dimensional PAGE (2D-PAGE) to Western blotting
and to mass spectrometry to characterize the p17 fraction. Two acidic
immunodominant but minority protein spots were recognized by APA17 and by bovine
sera. These antigens of 17 and 33 kDa are respectively composed of 4 and 2
isoforms. Furthermore, p17 isolation by 2D-PAGE and peptide sequencing by tandem
mass spectrometry yielded a partial sequence of 17 amino acids, which allowed the
putative amino terminal region of the NcGRA7 protein to be identified
unambiguously. The NcGRA7 protein, without the putative signal peptide at the NH2
terminus, was cloned and expressed in Escherichia coli and when the purified
recombinant protein (rNcGRA7) was analysed by SDS-PAGE and mass spectrometry, 2
bands of 24 and 33 kDa were resolved and identified as NcGRA7. These results
demonstrate that the immunodominant 17 kDa antigen of N. caninum is encoded by
the NcGRA7 gene.
PMID- 17032480
TI - Simple epidemiological model predicts the relationships between prevalence and
abundance in ixodid ticks.
AB - We tested whether the prevalence of ticks can be predicted reliably from a simple
epidemiological model that takes into account only mean abundance and its
variance. We used data on the abundance and distribution of larvae and nymphs of
2 ixodid ticks parasitic on small mammals (Apodemus agrarius, Apodemus
flavicollis, Apodemus uralensis, Clethrionomys glareolus and Microtus arvalis) in
central Europe. Ixodes trianguliceps is active all year round, occurs in the
study area in the mountain and sub-mountain habitats only and inhabits mainly
host burrows and nests, whereas Ixodes ricinus occurs mainly during the warmer
seasons, occupies a large variety of habitats and quests for hosts outside their
shelters. In I. ricinus, the models with k values calculated from Taylor's power
law overestimated prevalences. However, if moment estimates of k corrected for
host number were used instead, expected prevalences of both larvae and nymphs I.
ricinus in either host did not differ significantly from observed prevalences. In
contrast, prevalences of larvae and nymphs of I. trianguliceps predicted by
models using parameters of Taylor's power law did not differ significantly from
observed prevalences, whereas the models with moment estimates of k corrected for
host number in some cases under-estimated relatively lower larval prevalences and
over-estimated relatively higher larval prevalences, but predicted nymphal
prevalences well.
PMID- 17032481
TI - The interaction between the amoeba Balamuthia mandrillaris and extracellular
matrix glycoproteins in vitro.
AB - Balamuthia mandrillaris, a soil amoeba, is the causative agent of Balamuthia
granulomatous amoebic encephalitis, a life-threatening brain infection. This
amoeba is acquired from contaminated soil and may enter the host through
cutaneous lesions or through nasal passages, migrating to the lungs or brain.
During invasion, B. mandrillaris has access to components of the extracellular
matrix (ECM) of the host. Therefore, we investigated the interaction of B.
mandrillaris with 3 ECM glycoproteins (collagen-I, fibronectin and laminin-1)
that are encountered in host connective tissues and at the basal lamina. Using
optical microscopy, amoeba association on ECM-coated surfaces was examined.
Binding of amoebae on laminin was greater than that on collagen or fibronectin.
Laminin-adhered B. mandrillaris exhibited elongated and spread forms, distinctive
from those observed for amoebae on a plastic surface. Collagen and fibronectin
adhered B. mandrillaris presented elongated shapes with cellular expansions.
Binding to collagen, fibronectin, or laminin was inhibited when amoebae were pre
treated with sialic acid. Treatment with galactose resulted in diminished binding
of amoebae on laminin, while mannose increased binding in all coating conditions
tested. Dependence of divalent cations on amoeba binding was demonstrated for
laminin-amoeba interaction. Collectively, the results indicate that B.
mandrillaris recognizes specific glycoproteins of the mammalian extracellular
matrix.
PMID- 17032482
TI - Sustained peripheral arterial insufficiency durably impairs normal and
regenerating skeletal muscle function.
AB - Peripheral vascular occlusive diseases are frequently observed in humans, and
studies with animal models have been largely used. However the effects of
sustained lower limb ischemia on normal and regenerating hindlimb skeletal
muscles are not well known in the mouse model. Therefore prolonged unilateral
hindlimb ligation was generated by femoral artery ligation. Normal (myotoxic
untreated) and regenerating (myotoxic-reated) ischemic muscles were studied by
analyses of the in situ contractile properties and histological parameters.
Concerning normal mouse muscles, we found that femoral artery ligation reduced
hindlimb perfusion and altered muscle structure and function. Thus 7 days after
ligation, maximal tetanic force was reduced by about 70%, (p < 0.05). By 56 days
after ligation, muscle weights and cross-section areas of muscle fibers were
still reduced (p < 0.05). Concerning myotoxic treated muscles, we report that
ligation reduced the recovery of muscle weight and maximal tetanic force and
increased fatigue resistance at 56 days (p < 0.05). In conclusion, our results
demonstrate that sustained peripheral arterial insufficiency in mice induces long
term as well as acute detrimental effects in both normal and regenerating
muscles.
PMID- 17032483
TI - Information, social support and anxiety before gastrointestinal endoscopy.
AB - OBJECTIVES: To examine Lazarus and Folkman's (1984) stress theory regarding the
effects of the stress mediators information and perceived social support on
anxiety (as the stress response) regarding gastrointestinal (GI) endoscopy (as
the stressor) in male and female patients of various age groups. DESIGN: Non
experimental design. METHODS: Structured interviews were conducted with 113
hospital out-patients about to undergo GI endoscopy. Participants indicated their
perceptions of how much support and how much clear and useful information they
had received from both their general practitioner (GP) and a patient information
leaflet developed in collaboration with health psychologists as well as their
perceptions of how much social support they had obtained from other patients,
family and friends. Anxiety was measured with a population-specific trait and
state adaptation of the Hospital anxiety and depression scale (HADS-A). RESULTS:
Psychometric exploration of the HADS-A revealed a single general anxiety factor.
The reliability of this factor was high, with Cronbach's alpha=0.91. The majority
of the sample experienced high anxiety levels. Gender, but not age, differences
emerged, showing females to be more anxious than males, F(1, 84)=5.68, p<.05. A
regression model built on stress theory was tested, with anxiety as the dependent
variable and 11 predictor variables. The model was significant with R(2)=0.452,
F(11, 47)=3.522 and p=0.001. CONCLUSIONS: The clarity, but not the amount, of
information and social support from important others, but not GPs, were both
mediating the stress experience of the patients by reducing their perceived
anxiety.
PMID- 17032484
TI - Coping with ovarian cancer risk: the moderating effects of perceived control on
coping and adjustment.
AB - OBJECTIVE: Although perceived control and coping have been studied across various
health conditions, these relationships have been less well studied in the context
of coping with cancer risk over time. The present study was a longitudinal study
of the effects of perceived control and problem-focused coping on changes in
psychological adjustment and behavioural outcomes among women at increased risk
for ovarian cancer. DESIGN AND METHODS: Eighty women enrolled in a familial
cancer risk assessment programme participated in this study. Assessments of
problem-focused coping, perceived control and distress were collected upon entry
into the programme and again at 3-month follow-up. Behavioural adherence to
screening during the 12-month period following programme entry was obtained from
clinic records. RESULTS: Using hierarchical regression analysis, we observed a
significant interaction between perceived control and problem-focused coping for
psychological distress, beta=0.94, p<.05. Specifically, problem-focused coping
was associated with increasing distress over time among women who perceived high
control. A significant control by coping interaction was also observed for
behavioural adherence to pelvic ultrasound and CA125 screening, such that women
who perceived high control and utilized problem-focused coping were less likely
to undergo screening. CONCLUSIONS: Under conditions of high perceived control,
problem-focused coping was associated with increasing distress as well as poorer
behavioural adherence. Thus, perceived control and problem-focused coping may not
always yield positive psychological or behavioural health outcomes. These
findings contribute to a greater understanding of how problem-focused coping and
perceived control may influence the course of adjustment to cancer risk over
time.
PMID- 17032485
TI - Sample size for regression analyses of theory of planned behaviour studies: case
of prescribing in general practice.
AB - OBJECTIVES: Interest has been growing in the use of the theory of planned
behaviour (TBP) in health services research. The sample sizes range from less
than 50 to more than 750 in published TPB studies without sample size
calculations. We estimate the sample size for a multi-stage random survey of
prescribing intention and actual prescribing for asthma in British general
practice. To our knowledge, this is the first systematic attempt to determine
sample size for a TPB survey. METHODS: We use two different approaches: reported
values of regression models' goodness-of-fit (the lambda method) and zero-order
correlations (the variance inflation factor or VIF method). Intra-cluster
correlation coefficient (ICC) is estimated and a socioeconomic variable is used
for stratification. We perform sensitivity analysis to estimate the effects of
our decisions on final sample size. RESULTS: The VIF method is more sensitive to
the requirements of a TPB study. Given a correlation of .25 between intention and
behaviour, and of .4 between intention and perceived behavioural control, the
proposed sample size is 148. We estimate the ICC for asthma prescribing to be
around 0.07. If 10 general practitioners were sampled per cluster, the sample
size would be 242. CONCLUSIONS: It is feasible to perform sophisticated sample
size calculations for a TPB study. The VIF is the appropriate method. Our
approach can be used with adjustments in other settings and for other regression
models.
PMID- 17032486
TI - An electronic diary assessment of the effects of distraction and attentional
focusing on pain intensity in chronic low back pain patients.
AB - OBJECTIVE: The present study examined the effects of a manipulation of attention
to pain (i.e. attentional focusing vs. distraction) on pain intensity in daily
life of patients with chronic low back pain. It was hypothesized that attentional
focusing would lead to decreased pain intensity in high pain fearful individuals,
whereas distraction from pain would be associated with decreased pain intensity
in low pain fearful individuals. DESIGN: An experience sampling methodology was
used to examine the effects of a manipulation of attention to pain on pain
intensity in daily life of pain patients. METHODS: A total number of 38 patients
with chronic low back pain participated in this study and carried a palmtop
computer for 2 weeks. During this period, patients were 'beeped' 8 times a day to
complete diary questions. On certain days, instructions to either attend to or
distract from pain were given. RESULTS: Multi-level analyses showed that
attentional focusing was not associated with decreased pain intensity in high
pain fearful individuals and that distraction did not lead to decreased pain
intensity in low pain fearful individuals. The manipulations in isolation neither
influenced pain intensity. The manipulation check was generally weak. CONCLUSION:
A manipulation of attention to pain in daily life of patients with chronic low
back pain proved difficult to accomplish. As the manipulation check was generally
unsuccessful, no clear inferences about the underlying theory can be made. Future
research within the field of pain treatments (e.g. in vivo exposure) might
benefit greatly from electronic diary assessments studies.
PMID- 17032487
TI - Predicting perceived vulnerability for breast cancer among women with an average
breast cancer risk.
AB - OBJECTIVES: The purpose of the present study was to investigate predictors of
perceived vulnerability for breast cancer in women with an average risk for
breast cancer. On the basis of empirical findings that suggested which variables
might be associated with perceived vulnerability for breast cancer, we
investigated whether knowledge of breast cancer risk factors, cancer worry,
intrusions about breast cancer, optimism about not getting cancer and perceived
health status have a predictive value for perceived breast cancer vulnerability.
DESIGN: In a 3-step approach, we recruited 292 women from the general public in
Germany who had neither a family history of breast cancer nor breast cancer
themselves. After receiving an initial informational letter about study
objectives, the women were interviewed by telephone and then asked to fill in a
self-administered questionnaire. METHODS: We used structural equation modelling
and hypothesized that each of the included variables has a direct influence on
perceived vulnerability for breast cancer. RESULTS: We found a valid model with
acceptable fit indices. Optimism about not getting cancer, intrusions about
breast cancer and women's perceived health status explained 32% of the variance
of perceived vulnerability for breast cancer. Cancer worry and knowledge about
breast cancer did not influence perceived vulnerability for breast cancer.
CONCLUSION: Perceived vulnerability for breast cancer is associated with health
related variables more than with knowledge about breast cancer risk factors.
PMID- 17032488
TI - Mind the gap... in intelligence: re-examining the relationship between inequality
and health.
AB - Wilkinson contends that economic inequality reduces the health and life
expectancy of the whole population but his argument does not make sense within
its own evolutionary framework. Recent evolutionary psychological theory suggests
that the human brain, adapted to the ancestral environment, has difficulty
comprehending and dealing with entities and situations that did not exist in the
ancestral environment and that general intelligence evolved as a domain-specific
adaptation to solve evolutionarily novel problems. Since most dangers to health
in the contemporary society are evolutionarily novel, it follows that more
intelligent individuals are better able to recognize and deal with such dangers
and live longer. Consistent with the theory, the macro-level analyses show that
income inequality and economic development have no effect on life expectancy at
birth, infant mortality and age-specific mortality net of average intelligence
quotient (IQ) in 126 countries. They also show that an average IQ has a very
large and significant effect on population health but not in the evolutionarily
familiar sub-Saharan Africa. At the micro level, the General Social Survey data
show that, while both income and intelligence have independent positive effects
on self-reported health, intelligence has a stronger effect than income. The data
collectively suggest that individuals in wealthier and more egalitarian societies
live longer and stay healthier, not because they are wealthier or more
egalitarian but because they are more intelligent.
PMID- 17032489
TI - Predicting self-efficacy using illness perception components: a patient survey.
AB - OBJECTIVES: To assess the measures of illness representation components in
predicting measures of self-efficacy in patients with coronary heart disease.
DESIGN: A longitudinal design was adopted with predictor variables and dependent
variables (general self-efficacy, diet self-efficacy and exercise self-efficacy)
measured twice while participants were in hospital and 9 months following
discharge. Change scores of the predictor variables can be calculated and
dependent variables at baseline can be controlled. METHOD: A cohort sample of 300
patients admitted to hospital with coronary heart disease were given the
questionnaire measuring their illness perception (illness representation
components: identity, consequences, timeline and control/cure and outcome
expectation for diet and exercise); self-efficacy (general, diet and exercise
self-efficacy measures), demographic and illness characteristics and attendance
on a cardiac rehabilitation programme. The patients were asked to complete the
questionnaire in hospital before discharge following their cardiac diagnosis, and
again, 9 months later, when participants were expected to be functioning
independently of any rehabilitation programme. RESULTS: Demographic and illness
characteristics were found to have a more significant relationship with illness
representation components than with specific self-efficacy. The relationship
between illness representation components and specific self-efficacy changes
overtime, consequence and timeline were significantly related to self-efficacy
measures initially; however, symptom and control/cure were the variables that
were significantly related to self-efficacy measures 9 months later. After
statistically controlling individuals' baseline self-efficacy measures,
demographic and illness characteristic effects, symptom and control/cure were
found to make significant contributions to exercise and diet self-efficacy,
respectively, 9 months later. CONCLUSION: A significant relationship exists
between illness representation and self-efficacy. There is potential to integrate
both approaches to the assessment of psychosocial factors to provide effective
individualized care in cardiac rehabilitation.
PMID- 17032490
TI - Future-directed thinking and depression in relapsing-remitting multiple
sclerosis.
AB - BACKGROUND: Research has shown that depression is associated with a view of the
future characterized by reduced anticipation of future positive experiences, but
not necessarily increased anticipation of future negative experiences. The aim of
the present study was to investigate how participants with relapsing-remitting
multiple sclerosis (MS) anticipated their future in terms of positive and
negative events. DESIGN: A mixed design compared three groups of participants on
a measure of future thinking using an adapted verbal fluency paradigm. METHODS:
Depressed MS participants (N=14), non-depressed MS participants (N=28) and
healthy control participants (N=26) were assessed on their ability to generate
future positive and negative experiences. A content analysis was also conducted
on the responses generated by the MS depressed and MS non-depressed groups
according to whether or not they were related to MS. RESULTS: The MS depressed
group anticipated significantly fewer future positive events than the healthy
control group and the MS non-depressed group. The three groups did not differ in
the total numbers of anticipated future negative events, though the MS depressed
group did anticipate a significantly higher proportion of MS-related negative
events. CONCLUSIONS: Like depressed but physically healthy individuals, the MS
depressed group was characterized by a lack of positive thoughts about the
future, rather than an increased number of negative thoughts. The clinical
implications of these findings are discussed along with recommendations for
future research.
PMID- 17032491
TI - Targets and dimensions of social comparison among people with spinal cord injury
and other health problems.
AB - The present research examined comparison targets and comparison dimensions among
two Spanish samples of individuals facing serious illnesses and diseases. In
Study 1, 90 older patients (mean age 66.36) with various age-related diseases,
particularly cardiovascular diseases and diabetes, indicated that they compared
themselves most often with others with the same disease, next with others with
another disease and least with people without health problems. They compared
themselves more often on their mental state, symptoms and physical activities
than on their social activities. Social comparison orientation (SCO) as an
individual difference characteristic was associated with more frequent
comparisons with particularly similar targets, and with more frequent comparisons
of one's symptoms and physical activities. Neuroticism was correlated only with
more comparisons of one's symptoms. Study 2 was conducted in a sample of 70
relatively young patients (mean age 43.97) with spinal cord injury (SCI).
Overall, they compared themselves more often with others than the participants in
Study 1, and they compared themselves to a similar extent with people with SCI as
with people with another disease and with people without health problems. While
they felt on average better off than people with other diseases and other people
with SCI, people with SCI felt on average worse off than people without health
problems. They compared themselves more often on physical activities than on any
other dimension. Higher levels of stress and uncertainty were associated with
more frequent comparisons with people without SCI, and with more frequent
comparisons of one's mental state, one's symptoms and one's future perspectives.
The discussion focuses on the theoretical relevance of the results for social
comparison theory, and on the practical relevance of the findings for
interventions.
PMID- 17032492
TI - Psychological distress after the occupation: A community cross-sectional survey
from Lebanon.
AB - OBJECTIVES: Jezzine inhabitants were exposed to war stressors for 17 years. This
study aims at determining the prevalence of psychiatric distress (PD) among
Jezzine citizens who were exposed to war for 17 years and to identify associated
factors. DESIGN: Cross-sectional study. METHODS: A sample of 142 citizens was
randomly selected from a population of 5,000. A novel questionnaire was used to
collect data on war exposure, socioeconomic and demographic variables. PD was
assessed using GHQ-12. Data were analysed by logistic regression. RESULTS: PD was
found in 26% of Jezzine residents. PD was associated with age, marital status,
education, experience of war-related events, chronic illness and alcohol
drinking. After adjusting for all variables, PD remained significantly correlated
with older age and low education (odds ratios were 7.59 and 4.28, respectively).
CONCLUSIONS: The prevalence of PD among the residents of Jezzine after a year of
the Israeli withdrawal was similar to that reported in other communities whether
they were, or were not, exposed to war stress. Higher prevalence among older and
less educated individuals suggests the presence of a significant age cohort
effect and cognitive construal factors for PD among persons chronically exposed
to war-related stressors.
PMID- 17032493
TI - The meaning of self-perception of health in the UK armed forces.
AB - OBJECTIVES: We assessed the characteristics of self-perception of health (SPH) in
relation to psychological distress and physical symptoms, and willingness of
servicemen to see their Medical Officer (MO) by their SPH rating. DESIGN: We
randomly selected 4,500 servicemen to receive either a full or an abridged
screening questionnaire. MEASURES: The full questionnaire included 6 items from
the short-form 36 and the question on SPH, the General Health Questionnaire-12,
the post-traumatic stress disorder checklist and 15 symptoms. The abridged
questionnaire included a subset of items from the full questionnaire. All 'screen
positive' and a random 'screen-negative' sample were invited to see an MO.
RESULTS: 67.1% out of 4,500 servicemen completed the questionnaires. SPH was
strongly associated with a summary short form-36 (SF-36) measure. There was a
strong association between SPH and all assessment scales regardless of length of
the questionnaires (p<.001). Even among those with very good or excellent SPH,
high scores denoting psychological distress were prevalent (8.1%). Good SPH
provided the largest variations in symptoms and scores. Servicemen with a
poor/fair SPH were no more likely to accept a visit to the MO than the rest.
CONCLUSIONS: SPH is an excellent question for surveillance because it is highly
associated with psychological health but, at an individual level, it may convey
different meanings depending on the person's individual interpretation of the
term health. Symptomatic social avoidance may be high among servicemen who have a
poor/fair SPH and methods, such as buddy support, may be helpful in decreasing
isolation among those who may need professional support.
PMID- 17032494
TI - Longitudinal gains in self-regulation from regular physical exercise.
AB - OBJECTIVES: The purpose of the present study was to test whether the repeated
practice of self-regulation could improve regulatory strength over time. METHOD:
Regulatory performance was assessed at baseline, then at monthly intervals for a
period of 4 months using a visual tracking task. Perceived stress, emotional
distress, self-efficacy and general regulatory behaviour were assessed by
questionnaire. Following a 2-month control phase, participants entered a 2-month
self-regulation programme designed to increase regulatory strength: a programme
of regular physical exercise. RESULTS: Relative to the control phase,
participants who exercised showed significant improvement in self-regulatory
capacity as measured by an enhanced performance on the visual tracking task
following a thought-suppression task. During the regulatory exercise phase,
participants also reported significant decreases in perceived stress, emotional
distress, smoking, alcohol and caffeine consumption, and an increase in healthy
eating, emotional control, maintenance of household chores, attendance to
commitments, monitoring of spending and an improvement in study habits. The
control phase showed no systematic changes in performance on the visual tracking
task across sessions. Reports of perceived stress, emotional distress and
regulatory behaviours were also stable across sessions. CONCLUSIONS: The uptake
and maintenance of an exercise programme over a 2-month period produced
significant improvements in a wide range of regulatory behaviours. Nearly every
major personal and social problem has some degree of regulatory failure. The idea
that the capacity for self-regulation can be improved is therefore of vast
practical importance.
PMID- 17032495
TI - Effect of intratumoral injection on the biodistribution and the therapeutic
potential of HPMA copolymer-based drug delivery systems.
AB - The direct intratumoral (i.t.) injection of anticancer agents has been evaluated
extensively in the past few decades. Thus far, however, it has failed to become
established as an alternative route of administration in routine clinical
practice. In the present report, the impact of i.t. injection on the
biodistribution and the therapeutic potential of N-(2
hydroxypropyl)methacrylamide (HPMA) copolymer-based drug delivery systems was
investigated. It was found that, compared to intravenous injection, both the
tumor concentrations and the tumor-to-organ ratios of carriers improved
substantially. In addition, compared to intravenously and intratumorally applied
free doxorubicin and to intravenously applied poly(HPMA)
glycylphenylalanylleucylglycine-doxorubicin, intratumorally injected poly(HPMA)
glycylphenylalanylleucylglycine-doxorubicin presented a significantly increased
antitumor efficacy, as well as an improved therapeutic index. Based on these
findings, we propose intratumorally injected carrier-based chemotherapy as an
interesting alternative to routinely used chemotherapy regimens and routes of
administration.
PMID- 17032496
TI - Noninvasive optical tracking of red fluorescent protein-expressing cancer cells
in a model of metastatic breast cancer.
AB - We have evaluated the use of the Xenogen IVIS 200 imaging system for real-time
fluorescence protein-based optical imaging of metastatic progression in live
animals. We found that green fluorescent protein-expressing cells (100 x 10(6))
were not detectable in a mouse cadaver phantom experiment. However, a 10-fold
lower number of tdTomato-expressing cells were easily detected. Mammary fat pad
xenografts of stable MDA-MB-231-tdTomato cells were generated for the imaging of
metastatic progression. At 2 weeks postinjection, barely palpable tumor burdens
were easily detected at the sites of injection. At 8 weeks, a small contralateral
mammary fat pad metastasis was imaged and, by 13 weeks, metastases to lymph nodes
were detectable. Metastases with nodular composition were detectable within the
rib cage region at 15 weeks. 3-D image reconstructions indicated that the
detection of fluorescence extended to approximately 1 cm below the surface. A
combination of intense tdTomato fluorescence, imaging at > or = 620 nm (where
autofluorescence is minimized), and the sensitivity of the Xenogen imager made
this possible. This study demonstrates the utility of the noninvasive optical
tracking of cancer cells during metastatic progression with endogenously
expressed fluorescence protein reporters using detection wavelengths of > or =
620 nm.
PMID- 17032497
TI - Human cytomegalovirus infection alters PC3 prostate carcinoma cell adhesion to
endothelial cells and extracellular matrix.
AB - The genome and antigens of human cytomegalovirus (HCMV) are frequently found in
prostatic carcinoma. However, whether this infection is causative or is an
epiphenomenon is not clear. We therefore investigated the ability of HCMV to
promote metastatic processes, defined by tumor cell adhesion to the endothelium
and extracellular matrix proteins. Experiments were based on the human prostate
tumor cell line PC3, either infected with the HCMV strain Hi (HCMV(Hi)) or
transfected with cDNA encoding the HCMV-specific immediate early protein IEA1
(UL123) or IEA2 (UL122). HCMV(Hi) upregulated PC3 adhesion to the endothelium and
to the extracellular matrix proteins collagen, laminin, and fibronectin. The
process was accompanied by enhancement of beta(1)-integrin surface expression,
elevated levels of integrin-linked kinase, and phosphorylation of focal adhesion
kinase. IEA1 or IEA2 did not modulate PC3 adhesion or beta(1)-integrin
expression. Based on this in vitro model, we postulate a direct association
between HCMV infection and prostate tumor transmigration, which is not dependent
on IEA proteins. Integrin overexpression, combined with the modulation of
integrin-dependent signalling, seems to be, at least in part, responsible for a
more invasive PC3(Hi) tumor cell phenotype. Elevated levels of c-myc found in
IEA1-transfected or IEA2-transfected PC3 cell populations might promote further
carcinogenic processes through accelerated cell proliferation.
PMID- 17032498
TI - Overexpression of PIAS3 suppresses cell growth and restores the drug sensitivity
of human lung cancer cells in association with PI3-K/Akt inactivation.
AB - Constitutively activated signal transducers and activators of transcription
(STAT) are reported to cause uncontrolled transmission of growth signals. In this
study, we analyzed the roles of an inhibitor of STAT, protein inhibitor of
activated STAT (PIAS) 3, in the development of lung cancer. Treatment with an
inhibitor of phosphatidylinositol 3-kinase, LY294002, retarded the growth of
human lung cancer cells and rendered them more sensitive to chemotherapeutic
agents. However, the inhibition of JAK/STAT by AG490 significantly suppressed
cell growth but did not increase drug sensitivity at all. Overexpression of PIAS3
not only significantly inhibited cell growth but also rendered cancer cells up to
12.0-fold more sensitive to the above drugs, which was associated with the
suppression of Akt phosphorylation. Inhibition of PIAS3 with small interfering
RNA, nevertheless, led cancer cells to accelerate cell proliferation, deteriorate
chemosensitivity, and augment Akt phosphorylation. Although the overexpression of
suppressors of cytokine signaling 3 in cancer cells also inhibited cell growth
and STAT3 phosphorylation, it neither increased sensitivity to chemotherapeutic
drugs nor affected the phosphorylation of Akt. These results indicate that PIAS3
may be an attractive candidate for targeting the JAK/STAT and PI3-K/Akt signaling
pathways in cancer treatment.
PMID- 17032499
TI - TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy
number changes in prostate carcinomas and paired HGPIN lesions.
AB - TMPRSS2-ETS gene fusions have been found recurrently in prostate carcinomas, but
not in the presumed precursor lesion, high-grade prostatic intraepithelial
neoplasia (HGPIN). However, HGPIN lesions may share chromosomal changes with
prostate cancer. To determine the relative order of genetic events in prostate
carcinogenesis, we have analyzed 34 prostate carcinomas, 19 paired HGPIN lesions,
14 benign prostate hyperplasias, and 11 morphologically normal prostatic tissues
for TMPRSS2-ERG and TMPRSS2-ETV1 rearrangements and genomic imbalances. TMPRSS2
exon 1 was fused in-frame with ERG exon 4 in 17 of 34 (50%) prostate carcinomas
and in 4 of 19 (21%) HGPIN lesions, but in none of controls. The findings were
further validated by sequencing analysis and by the real-time polymerase chain
reaction quantification of TMPRSS2-ERG fusion transcript and the ERG exons
5/6:exons 1/2 expression ratio. Chromosome copy number changes were detected by
comparative genomic hybridization in 42% of clinically confined carcinomas and in
none of the 16 HGPIN lesions analyzed. We demonstrate for the first time that the
TMPRSS2-ERG fusion gene can be detected in a proportion of HGPIN lesions and that
this molecular rearrangement is an early event that may precede chromosome-level
alterations in prostate carcinogenesis.
PMID- 17032500
TI - Tumor mRNA-transfected dendritic cells stimulate the generation of CTL that
recognize neuroblastoma-associated antigens and kill tumor cells:
immunotherapeutic implications.
AB - Several observations suggest a potential role of T-cell-mediated immunity in the
control of neuroblastoma (NB). However, the generation of NB-specific cytotoxic T
lymphocytes (CTL) on T-cell priming with tumor mRNA-transfected dendritic cells
(DC) has never been investigated before. In the present study, the feasibility of
this strategy has been analyzed, both in healthy donors and in NB patients.
Monocyte-derived DC were raised from three human leukocyte antigen (HLA) A2+ NB
patients and seven HLA-A1+ or HLA-A2+ healthy donors transfected with mRNA from
four NB cell lines and cocultured with autologous CD8+ lymphocytes. Expanded CTL
expressed an effector/memory phenotype and a T cytotoxic 1-like profile of
cytokine secretion. CTL specificity was demonstrated by interferon-gamma release
on incubation with HLA-matched NB cell lines. The latter cell lines, but not
autologous T-cell blasts, were lysed by CTL in an HLA-restricted manner.
Cytotoxicity was found to involve the release of granzyme B. When tested for
reactivity against NB-associated antigens, CTL from normal individuals recognized
anaplastic lymphoma-associated kinase (ALK) and preferentially expressed antigen
of melanoma (PRAME) peptides only, whereas patients' CTL reacted also to
survivin, telomerase, and tyrosine hydroxylase peptides. This study demonstrates
that DC transfected with NB mRNA induce the generation of patients' CTL specific
for different NB-associated antigens, supporting the feasibility of NB T-cell
immunotherapy.
PMID- 17032501
TI - Expression of calcium-binding proteins S100A2 and S100A4 in Barrett's
adenocarcinomas.
AB - In this study, we investigated the mRNA and protein expression of S100A2 and
S100A4 in adenocarcinomas of the stomach and esophagus. Real-time reverse
transcription-polymerase reaction analysis on 72 tumors revealed frequent
overexpression of S100A2 and S100A4 in Barrett's adenocarcinomas (BAs) (P < .01).
Immunohistochemical analysis on tumor tissue microarrays that contained 187
tumors showed absent to weak staining for S100A2 in all normal gastric mucosa
samples, whereas normal esophageal mucosa samples demonstrated moderate to strong
nuclear staining. Contrary to the nuclear expression of S100A2 in normal
esophageal mucosa, two thirds of Barrett's dysplasia and BAs that overexpressed
S100A2 demonstrated stronger cytosolic staining than nuclear staining (P < .001).
Overexpression of S100A2 protein was more frequently seen in well-differentiated
tumors than in others (P = .02). Moderate to strong staining of S100A4 was
detected in two thirds of tumors and was frequently observed in the presence of
Barrett's esophagus (P = .02). Similar to S100A2, the expression of S100A4 was
predominantly cytosolic in two thirds of the tumors (P = .001). There was a
significant correlation between S100A4 overexpression and lymph node metastasis
(N(2)-N(4)) (P = .027). These results demonstrate frequent cytosolic
overexpression of S100A2 and S100A4 in BAs. Further studies are ongoing to
understand the biological significance of these S100A proteins in Barrett's
tumorigenesis.
PMID- 17032502
TI - Cellular and molecular consequences of peroxisome proliferator-activated receptor
gamma activation in ovarian cancer cells.
AB - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand
activated transcription factor. In addition to its canonical role in lipid and
glucose metabolism, PPAR-gamma controls cell proliferation, death, and
differentiation in several tissues. Here we have examined the expression of PPAR
gamma in ovarian tumors and the cellular and molecular consequences of its
activation in ovarian cancer cells. PPAR-gamma was expressed in a large number of
epithelial ovarian tumors and cell lines. The PPAR-gamma ligand ciglitazone
inhibited the growth and clonogenic survival of ovarian cancer cells, inducing
cell cycle arrest and cell death. Growth inhibition by ciglitazone was reversed
by the PPAR-gamma antagonist GW9662, indicating the involvement of PPAR-gamma
dependent mechanisms. Microarray-based gene profiling revealed complex changes in
the transcriptional program of ovarian cancer cells on treatment with ciglitazone
and identified multiple pathways that may contribute to PPAR-gamma ligands'
antitumor activity. Genes upregulated by ciglitazone were predominantly
associated with metabolic, differentiation, and tumor-suppressor pathways,
whereas downregulated genes were involved in cell proliferation, cell cycle, cell
organization, and steroid biosynthesis. Collectively, our data indicate that PPAR
gamma activation by selective agonists is a valid strategy for ovarian cancer
therapy and prevention, and should be tested alone and in combination with other
anticancer drugs.
PMID- 17032504
TI - Heparanase expression in malignant salivary gland tumors inversely correlates
with long-term survival.
AB - BACKGROUND: Upregulation of the endo-beta-D-glucuronidase, heparanase, was noted
in an increasing number of human malignancies. Heparanase expression correlated
with enhanced local and distant metastatic spread, increased vascular density,
and reduced postoperative survival. PATIENTS AND METHODS: We analyzed heparanase
expression in 60 patients (aged 59 +/- 17 years) with malignant salivary tumors
(39 males and 21 females) using immunohistochemistry. We applied antiheparanase
antibody 733, which has previously been shown to preferentially recognize a 50
kDa active heparanase subunit over a 65-kDa latent enzyme. Thus, immunostaining
can directly be correlated with enzymatic activity. RESULTS: Heparanase staining
was positive (> 0) in 70% of tumors (42 of 60 patients) and was negative (0) in
the remaining 30% (18 patients). The cumulative survival of patients diagnosed as
heparanase-negative (n = 18) at 300 months was 70% (95% confidence interval = 35
88). In contrast, the cumulative survival of patients diagnosed as heparanase
positive (n = 42) at 300 months was 0% (statistically significant difference, P =
.035). CONCLUSIONS: Heparanase expression levels inversely correlate with the
survival rates of salivary gland cancer patients, clearly indicating that
heparanase is a reliable prognostic factor for this malignancy and an attractive
target for anticancer drug development.
PMID- 17032503
TI - Inhibition of androgen-independent prostate cancer by estrogenic compounds is
associated with increased expression of immune-related genes.
AB - The clinical utility of estrogens for treating prostate cancer (CaP) was
established in the 1940s by Huggins. The classic model of the anti-CaP activity
of estrogens postulates an indirect mechanism involving the suppression of
androgen production. However, clinical and preclinical studies have shown that
estrogens exert growth-inhibitory effects on CaP under low-androgen conditions,
suggesting additional modes whereby estrogens affect CaP cells and/or the
microenvironment. Here we have investigated the activity of 17beta estradiol (E2)
against androgen-independent CaP and identified molecular alterations in tumors
exposed to E2. E2 treatment inhibited the growth of all four androgen-independent
CaP xenografts studied (LuCaP 35V, LuCaP 23.1AI, LuCaP 49, and LuCaP 58) in
castrated male mice. The molecular basis of growth suppression was studied by
cDNA microarray analysis, which indicated that multiple pathways are altered by
E2 treatment. Of particular interest are changes in transcripts encoding proteins
that mediate immune responses and regulate androgen receptor signaling. In
conclusion, our data show that estrogens have powerful inhibitory effects on CaP
in vivo in androgen-depleted environments and suggest novel mechanisms of
estrogen-mediated antitumor activity. These results indicate that incorporating
estrogens into CaP treatment protocols could enhance therapeutic efficacy even in
cases of advanced disease.
PMID- 17032505
TI - Contraception in crisis.
PMID- 17032506
TI - Tackling the unacceptable: Nigeria approves misoprostol for postpartum
haemorrhage.
PMID- 17032507
TI - Abortion law: campaign groups and the quest for change.
PMID- 17032508
TI - Accessibility of condoms to young people in Manchester, UK.
AB - BACKGROUND AND METHODOLOGY: Issues relevant to the accessibility of male condoms
for young people in the Greater Manchester area (UK) were investigated, using
semi-structured, in-depth interviews and a questionnaire survey. RESULTS: Family
planning clinics and condom vending machines (CVMs) were the most cited sources
for condom acquisition. Young people's knowledge of where and when they could
access condoms varied by age and gender. Suitable positioning of CVMs would need
to take such variations into account when targeting potential customers. Levels
of embarrassment about acquiring condoms also varied according to gender. The
lifestyles of young people indicated the sorts of places in which CVMs might
offer increased accessibility. For younger men and women this tended to involve
low-cost, semi-private places such as local parks, school toilets and shopping
malls/streets. Older men with higher spending power and increased confidence
could access condoms through pub and club toilets and chemist shops. CONCLUSIONS:
Accessible positioning of CVMs was related to the age, gender and lifestyle of
the participants, and programmes to enhance accessibility should reflect this.
Increased accessibility for younger groups, and especially women, needs to take
into account issues of cost, confidence and embarrassment. For older groups,
lifestyle choices indicated pubs and clubs as key locations for both men and
women.
PMID- 17032509
TI - The importance of contextualisation in giving a diagnosis of genital chlamydial
infection: findings from a qualitative study.
AB - OBJECTIVE: To explore the impact of diagnostic communication upon the way in
which people receive and respond to a diagnosis of chlamydial infection. METHODS:
A qualitative study examining the responses of individuals to a diagnosis of
chlamydial infection. The study was conducted in a genitourinary medicine clinic
and a family planning clinic in the Midlands region of the UK. The sample size
was 50 and included both males and females. Data collection was by means of
unstructured interviews, which were audio-taped and fully transcribed. The
principles of grounded theory were followed in the sampling, analysis and
exploration of the literature. RESULTS: A diagnosis of chlamydial infection was
commonly unexpected and associated with negative reactions, which derived from
the social construction of sexually transmitted infections as evidence of
breaching the moral code. The way in which the health professional communicated
the diagnosis contributed to the patient response, either negatively by
reinforcing feelings of self-recrimination or positively by the provision of key
information that appeared to be helpful in modifying that response. CONCLUSION:
Sensitive management and the provision of contextualised information serve an
important function for those diagnosed with chlamydial infection.
PMID- 17032511
TI - Low literacy: a hidden problem in family planning clinics.
AB - OBJECTIVES: Low literacy is highly prevalent among UK adults. This study assessed
functional health literacy among family planning clinic clients and whether this
was associated with sexual health knowledge and behaviours. It also assessed the
readability of patient leaflets. METHODS: 505 female family planning clinic
attendees aged 16-35 years were interviewed about their sexual behaviour and
knowledge. Their reading age was assessed using a validated test (REALM). The
readability of leaflets on contraception supplied to clinic users was measured.
RESULTS: All respondents had a reading age of 12 years and above, 221 (43.8%)
between 12 and 14 years and 284 (56.2%) greater than 14 years. Those in the lower
literacy group were significantly more likely to have been aged under 16 years at
time of first sexual intercourse, and significantly less likely to know the most
fertile time of the menstrual cycle, to identify sexually transmitted infections
and to know that sexual infections can be transmitted through oral and anal sex.
The reading age of information leaflets in the clinics ranged from 11 to 17
years. Thus, clients with a reading level of 12-14 years would have difficulty in
understanding some of the leaflets. CONCLUSIONS: Functional health literacy is
related to sexual behaviour and knowledge. Written information should be prepared
with this in mind and other routes of communication considered.
PMID- 17032512
TI - Consumer behaviour and contraceptive decisions: resolving a decades-long puzzle.
PMID- 17032510
TI - Quality of delivery of the Standard Days Method as compared with contraceptive
pills in Rwanda.
AB - BACKGROUND AND METHODOLOGY: Replicating a Peruvian study, this research
introduced the Standard Days Method (SDM) into Rwanda Ministry of Health clinics
and evaluated client counselling on the new method against that given for
contraceptive pills. Providers received technical reinforcement concerning
established methods in addition to SDM training. To evaluate their quality of
care, simulated clients implemented a service test in visits to 20 clinics.
RESULTS: As in Peru, providers exchanged significantly more relevant information
with clients who chose SDM than with those who chose pills. Also, a minority of
providers posed barriers to SDM access by refusing to give SDM tools to the
client until she brought her partner for consultation. CONCLUSIONS: The findings
of this study confirm that SDM counselling is generally satisfactory, although
SDM training needs adjustment, and that the rigour of providers' pill counselling
remains below capacity.
PMID- 17032517
TI - Reproductive health in domestic animals.
PMID- 17032518
TI - Delphi method and nominal group technique in family planning and reproductive
health research.
PMID- 17032519
TI - Primary ovarian pregnancy with a levonorgestrel intrauterine system.
PMID- 17032520
TI - Implanon and alopecia.
PMID- 17032521
TI - Premenstrual syndrome: a plea for greater understanding.
PMID- 17032522
TI - Are your patients' emotions blocking their understanding?
PMID- 17032523
TI - Obtaining valid consent.
PMID- 17032524
TI - "Clean-up consultant to aisle 69 please".
PMID- 17032525
TI - In condoms we trust: to each, one's own.
PMID- 17032527
TI - The French pox.
PMID- 17032528
TI - Liquid-based cytology.
PMID- 17032529
TI - Increase in IUD expulsions.
PMID- 17032530
TI - Oral contraceptives and diabetes mellitus: an update.
PMID- 17032532
TI - Full-term pregnancy with Implanon in situ.
PMID- 17032533
TI - Full-term pregnancy with Implanon in situ.
PMID- 17032534
TI - Full-term pregnancy with Implanon in situ.
PMID- 17032535
TI - Implanon insertion.
PMID- 17032538
TI - Pelvic actinomycosis.
PMID- 17032541
TI - Genetic influences on free and cued recall in long-term memory tasks.
AB - Long-term memory (LTM) problems are associated with many psychiatric and
neurological illnesses and are commonly measured using free and cued recall
tasks. Although LTM has been linked with biologic mechanisms, the etiology of
distinct LTM tasks is unknown. We studied LTM in 95 healthy female twin pairs
identified through birth records in the state of Missouri. Performance on tasks
of free recall of unrelated words, free and cued recall of categorized words, and
the vocabulary section of the Wechsler Adult Intelligence Scale (WAIS-R) were
examined using structural equation modeling. Additive genetic and unique
environmental factors influenced LTM and intelligence. Free recall of unrelated
and categorized words, and cued recall of categorized words, were moderately
heritable (55%, 38%, and 37%). WAIS-R vocabulary score was highly heritable
(77%). Controlling for verbal intelligence in multivariate analyses of recall,
two components of genetic influence on LTM were found; one for all three recall
scores and one for free and cued categorized word recall. Recall of unrelated and
categorized words is influenced by different genetic and environmental factors
indicating heterogeneity in LTM. Verbal intelligence is etiologically different
from LTM indicating that these two abilities utilize different brain functions.
PMID- 17032542
TI - Sex differences in symptoms of depression in unrelated individuals and opposite
sex twin and sibling pairs.
AB - Diagnosis of a major depressive episode by the Diagnostic and Statistical Manual
of Mental Disorders of the American Psychiatric Association requires 5 out of 9
symptoms to be present. Therefore, individuals may differ in the specific
symptoms they experience and reach a diagnosis of depression via different
pathways. It has been suggested that depressed women more often report symptoms
of sleep disturbance, appetite or weight disturbance, fatigue, feelings of
guilt/worthlessness and psychomotor retardation than depressed men. In the
current study, we investigate whether depressed men and women differ in the
symptoms they report. Two samples were selected from a sample of Dutch and
Australian twins and siblings. First, Dutch and Australian unrelated depressed
individuals were selected. Second, a matched epidemiological sample was created
consisting of opposite-sex twin and sibling pairs in which both members were
depressed. No sex differences in prevalence rates for symptoms were found, with
the exception of decreased weight in women in the sample of unrelated
individuals. In general, the similarities in symptoms seem to far out-weigh the
differences in symptoms between men and women. This signifies that men and women
are alike in their symptom profiles for major depression and genes for depression
are probably expressed in the same way in the two sexes.
PMID- 17032543
TI - Nonadditive genetic effects on hostility in South Korean adolescent and young
adult twins.
AB - Hostility has been shown to be a vulnerability marker for various health
problems. The present study examined genetic and environmental contributions to
individual differences in hostility in South Korean adolescent and young adult
twins. Seven hundred and nineteen same- and opposite-sex twin pairs aged from 13
to 23 years completed a hostility scale. The scalar sex-limitation model was
applied to the data. The best fitting model indicated that 34% of the total
variation of hostility was attributable to genetic factors operating in a
nonadditive manner. The remaining 66% of the variance was associated with
nonshared environmental influences and measurement error. These findings were
largely consistent with results from previous twin studies of personality based
on Caucasian twins, rendering support for the pervasive influence of genetic
nonadditivity on human personality traits and the generalization of the
heritability of personality across human populations.
PMID- 17032544
TI - Suicidal behavior in surviving co-twins.
AB - Recent research has provided strong support for the existence of a familial risk
for suicide, and efforts have been made to separate genetic from enviromental
risk factors. Twin studies have played a major role in the identification of
genetic factors, and the results indicate that the concordance rate for suicide
is higher in identical than in fraternal twins (Baldessarini & Hennen, 2004).
Moreover, Segal and Roy (1995) reported a significantly higher frequency of
nonfatal suicidal attempts by monozygotic (MZ) than by dyzygotic (DZ) twins whose
co-twins had committed suicide. However, doubts remain as to whether the
increased risk of suicide in MZ twins is a response to the intense grief over the
loss of a close relative, or whether a common genotype is associated with
suicidal behavior. Sudden loss, which may carry a stigma in the case of a
suicide, has been linked to increased persistent emotional stress and
physiological changes (Epstein, 1993; Martin & Dean, 1993). A number of
researchers have reported greater suicidal ideation among bereaved MZ twins as
compared to DZ twins, suggesting that a loss due to suicide may increase the risk
of suicidal behavior in the surviving co-twin (Segal & Bouchard, 1993; Segal &
Roy, 1995; Segal et al., 1995). The aim of the present article is to address the
issue of the intense grief experienced by twins after the co-twin suicide.
PMID- 17032545
TI - Body size in five-year-old twins: heritability and comparison to singleton
standards.
AB - The aim of this study is to examine causes of individual differences in height,
weight and body mass index (BMI) in 5-year-old children registered with the
Netherlands Twin Register. In addition, we examine whether the results of twin
studies can be expanded to the singleton population by comparing the data from
twins to Dutch reference growth data and by looking at the twins' target height,
which was derived from parental height. For 2996 5-year-old twin pairs,
information on height and weight and on parental height was available. Univariate
and bivariate genetic analyses of height and weight and univariate analyses of
BMI were conducted. In order to compare the twins to the singleton population,
standard deviation scores (SDS) for height, BMI and target height were calculated
based on Dutch reference growth charts for the general population from 1997.
Genetic influences were an important source of variation in height, weight and
BMI and the main source of covariation between height and weight. Additive
genetic factors accounted for 69% and 66% of the individual differences in height
in boys and girls, respectively. For weight, heritability estimates were 59% in
boys and 78% in girls and for BMI 34% and 74%. The influence of common
environment on height was 25% and 27%, on weight 24% and 10% and on BMI 44% and
12% in boys and girls. The bivariate model showed a large overlap between the
genes influencing height and weight. Genes explain 78% (in boys) and 76% (in
girls) of the covariance between weight and height. At the age of 5 years, female
twins were as tall as singleton children, while male twins were shorter than
singletons. For both boys and girls, however, mean height SDS was 0.6 standard
deviation scores below the mean target height. All twins had lower BMI than
singletons. Twins grow fairly well compared to singletons, but they grow below
their target height. This may be due to the above average height of twin parents.
PMID- 17032546
TI - Maternal dietary intake in twin pregnancies: does it diminish towards term?
AB - We tested the hypothesis that energy intake among women with twin pregnancies
decreases in late gestation, as the uterus enlarges and they become increasingly
uncomfortable. We asked women to recall dietary intake for the previous 24 hours,
every 2 weeks from around 29 weeks of gestation, using a photographic atlas and
other strategies to estimate portion size. Eighty women provided data at around
29, 31, 33 and 35 weeks of gestation. We calculated total energy intake, and
energy intake from carbohydrate, fat and protein. Data were log transformed to
reduce skewness. Using mixed effects linear regression models, we found minimal
evidence that total energy intake changed over this time period, either before or
after adjustment for potential confounding factors (95% confidence interval for
relative change per week: -1.4%, 0.6%). There was weak evidence of a small
decline in carbohydrate intake over time, both before and after controlling for
energy intake. We cannot exclude change in energy intake or diet composition
before 29 weeks or after 35 weeks of twin gestation.
PMID- 17032547
TI - Birthweight discordance in twins and the risk of being heavier for respiratory
distress syndrome.
AB - Twin pregnancies are becoming common as a result of increased assisted
reproduction. Studies have shown that the smaller twin of a pair is at greater
risk of morbidity and mortality. Our aim was to determine if there is a relation
between birth-weight discordancy and neonatal morbidity and mortality and to test
the occurrence of respiratory distress syndrome (RDS) in discordant twins. For 5
years all twins admitted to our intensive care unit were included in the study.
Discordance was calculated as the difference between twins' weights divided by
the heavier weight. Diagnosis of RDS was made by typical clinical and
radiographic methods. Multiple logistic regression was performed with gender,
weight order and birth order as the independent variables and RDS as the
dependent variable. Two hundred and sixty-six twin pairs with a mean gestation of
33 weeks and a mean birth-weight of 1890 g were evaluated. Multiple logistic
regression revealed that being the heavier twin was a more important risk factor
for RDS (odds ratio 4.5; 95% confidence interval 2.2-9.2) than being the male or
second-born twin. Based on neonatal outcomes a birth-weight discordance equal or
greater than 20% in twin pairs was accepted as the discordance criterion.
Discordant and concordant groups were statistically different in neonatal
mortality, necrotizing enterocolitis, polycytemia and hypoglycemia. Our data
demonstrated that being the heavier twin is a risk factor for RDS and a birth
weight difference of 20% or more in twin pairs should be accepted as discordance.
PMID- 17032548
TI - Curves of placental weights of live-born twins.
AB - The purpose of this study is to present curves of estimated placental growth in
twins and to evaluate the relative contribution of gestational age, zygosity,
chorionicity, fusion of the placentas, sex of the individual and of the twin
pair, site of the umbilical cord insertion, birth order, maternal age, and
parity. Perinatal data and placental data were obtained from 6315 live-born twin
pairs from the East Flanders Prospective Twin Survey. Of 4318 twin pairs, with no
missing values, the placental weights of different gestational ages were analyzed
using a nonlinear multivariate Gaussian regression. Two groups were
distinguished: (1) twins with two separate placentas, and (2) twins with only one
placental mass (one placenta in case of monochorionic twins or two fused
placentas in case of dichorionic placentas). Overall, placental weight was
influenced by gestational age, fusion of the placentas, and parity. In the case
of one placental mass, monozygotic dichorionic twins had the lowest weights. If
two separate placentas were present, birth order played a role in favor of the
first-born twin. For parity and zygosity, the differences were most pronounced
between 27 and 29 weeks, whereas the difference for birth order was most
pronounced between 33 and 37 weeks. In conclusion, basic physiological
characteristics, routinely examined at birth, influence placental weight. Taking
these covariates into account allows a better evaluation of the placental weight
given a gestational age, as an indicator of growth.
PMID- 17032549
TI - Twinning and risk of stillbirth subtypes in pediatric mothers.
AB - We sought to estimate levels of risk for stillbirth subtypes associated with twin
gestations among pediatric mothers (10-14 years). Analysis was on twin
pregnancies covering the period 1989 to 2000 in the United States. We classified
stillbirth as term, preterm, small-for-gestational-age (SGA) or preterm-SGA. We
then assessed the risks of these stillbirth subtypes in pediatric mothers using
two comparison groups consisting of women aged 15 to 19 years old (adolescent
mothers) and 20 to 24 years old (mature mothers). Adjusted risk estimates were by
means of hazard ratios generated from a Cox proportional hazards regression
model. We adjusted for dependence of observations within twin clusters using the
robust sandwich estimator. The rate of stillbirth was highest among pediatric
mothers (56/1000), followed by adolescent gravidas (29/1000) and lowest in mature
mothers (20/1000; p for trend < .01). Overall, preterm stillbirth was the most
frequent stillbirth phenotype while term stillbirth was the least frequent. Not a
single case of term stillbirth was recorded in pediatric mothers. Among pediatric
gravidas, the risk for preterm stillbirth was more than tripled (adjusted hazard
ratio [AHR] = 3.4; 95% confidence interval [CI] = 2.5-4.6), and that of preterm
SGA stillbirth more than doubled (AHR = 2.6; 95% CI = 1.8-3.7) that of mature
mothers respectively. The 30% risk elevation for SGA stillbirth among pediatric
mothers was not found to be statistically significant (AHR = 1.1; 95% CI = 0.3
4.3). Pediatric motherhood is a risk factor for stillbirth in twin gestation,
especially, preterm and preterm-SGA stillbirth phenotypes. Prevention of
stillbirth among this category of mothers should target the period preceding full
term.
PMID- 17032550
TI - Stillbirths in multiple births: test of independence.
AB - The stillbirth rate in twins is a more sensitive indicator of environmental
hazards than the stillbirth rate in singletons. Medical care or other
socioeconomic factors may be more influential for perinatal survival in twin than
in single deliveries. Studies have indicated that stillbirths among children in a
set of multiple maternities are not independent. Models were considered assuming
independent outcomes within a set of multiple maternities. Analyses of the
stillbirth rates confirm that the risk of stillbirth among males is almost
constantly higher than among females. Any model introduced should assume
different stillbirth rates for males and females. The models were tested with
both maximum likelihood and minimum chi2 methods. Data was analyzed from Sweden,
the Aland Islands, Saxony, England and Wales, and significant discrepancies
obtained from the independence models. The same-sexed twin data contain both
monozygotic and dizygotic twin sets with apparently different stillbirth rates.
Consequently, for same-sexed twins the proposed model could be considered too
simple. After improvement by splitting the same-sexed data into monozygotic and
dizygotic twin sets, the dependence still remains. The proportion of both same
sexed and opposite-sexed twin pairs that contain two stillborn is greater than
what the stillbirth rates and the independence should indicate. Consequently,
stillbirth rate estimates based on the relative frequency of twin sets with two
stillborn children have a positive bias. When the stillbirth rate decreases, the
number of sets with two stillborn children decreases more slowly than would be
indicated by independence.
PMID- 17032551
TI - Outcome of twins delivery; predictors for successful vaginal delivery: a single
center experience.
AB - The aim of this study was to compare maternal and neonatal outcome of twin births
according to mode of delivery and to isolate the factors predicting a successful
vaginal delivery and those predicting a failed trial of labor (TOL) leading to an
emergent cesarean section. We reviewed all twin deliveries during the years 1995
to 2004. Parameters studied include maternal age, parity, gestational age,
maternal antepartum complications and postpartum complications, fetal
presentations, birthweight, mode of delivery of each twin, Apgar scores and cord
pH. During the study period there were 40,710 deliveries of which 804 (1.9%) were
twin deliveries. Of the 804 twins, 398 (49.5%) had planned cesarean sections
(PCS) and 406 (50.5%) entered a TOL. Maternal age and parity were similar among
the groups. Neonatal outcomes and postpartum complications did not differ between
the groups. Of 406 women who had a TOL, 84.9% eventually delivered both twins
vaginally. A significantly higher percentage of antepartum complications were
noted among those who failed the TOL compared to those with successful TOL (8.2%
vs. 1.7%, p = .01). The number of neonates with pH of less than 7.0 did not
differ between the groups although more neonates (2.5% vs. 0.4%, p = .05) among
the failed TOL had an Apgar score of less than 7.0 at 5 minutes compared to
successful TOL. Vaginal delivery of both twins after TOL occurred in 91% of
vertex/vertex compared with 71.8% of vertex/nonvertex presenting twins (p < .01).
Neonatal outcomes did not differ between both groups. Our results indicate that
both vaginal and PCS are comparable options for vertex presenting first twin
regardless of second twin presentation.
PMID- 17032552
TI - Course of ovarian hyperstimulation syndrome in 19 intact twin pregnancies after
assisted reproduction techniques, with a case report of severe thromboembolism.
AB - Ovarian hyperstimulation syndrome (OHSS) is a serious complication of assisted
reproduction techniques using in vitro fertilization and intracytoplasmic sperm
injection (IVF/ICSI). Its etiology has still not yet been fully resolved. Human
chorionic gonadotrophin, administered exogenously as well as produced
endogenously during pregnancy, is responsible for the onset of OHSS, and high
levels of estradiol appear to worsen the condition. In this case series, the
course of mild to severe OHSS was evaluated in 19 intact twin pregnancies after
IVF/ICSI. Another serious complication associated with OHSS is thromboembolic
events. In these cases, the pregnancy can be protected through anticoagulation
treatment, but there may be exceptions to this. This series includes a case of
bilateral thrombosis of the internal and external jugular veins in the 7th
gestational week in a twin pregnancy after OHSS and ICSI, with termination of the
pregnancy in the 9th gestational week due to progressive thrombosis during
anticoagulation therapy.
PMID- 17032553
TI - An acephalus acardius amorphous fetus in a monochorionic pregnancy with sex
discrepancy.
AB - Acephalus acardia is among the most severe malformations described in fetuses,
with an incidence of about 1 in 35,000 births and is due to twin-to-twin
transfusion syndrome, frequently occurring in monochorionic twin pregnancies. The
severity of the syndrome depends upon the type of the anastomoses arising between
the vascular networks of the two fetuses, usually configuring the 'twin reverse
arterial perfusion syndrome'. No clear and univocal etiological explanation is
known, though few cases with chromosomal abnormalities have been reported so far.
In some cases the fusion of two or more separate placentae of dizygotic fetuses
occurs, leading to monochorionic twinning. Few cases of acardius amorphous with
complete autoptical examination have been described so far. We report a case of
acephalus acardius amorphus fetus, showing features of extremely severe sistemic
immaturity with very few structured organs. Defined external and autoptic
examinations have been performed on the dismorphic twin, along with the
histological examination of tissue samples. Kariotype analysis showed sex
discrepancy between the twins, as a normal female kariotype had been detected in
the acephalus acardius while the living co-twin was a normal healthy male. The
analysis of the placenta showed the vascular anomalies leading to the twin-to
twin transfusion syndrome.
PMID- 17032555
TI - Gastrointestinal stromal tumors: imatinib and beyond.
AB - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
the gastrointestinal tract. Clinicians previously classified GISTs as "benign" or
"malignant," but now place resected tumors in risk categories that are based on
size and mitotic rate. Historically, GIST patients were managed with surgery
alone, as chemotherapy and radiotherapy have minimal activity in this disease. In
the pre-imatinib era, patients with recurrent or metastatic disease generally did
very poorly. GIST therapy was revolutionized following the discovery of oncogenic
mutations in the c-kit gene, as well as in the platelet-derived growth factor
receptor. Subsequently, it has been confirmed that the KIT receptor tyrosine
kinase is both a diagnostic marker and a useful therapeutic target in GIST.
Imatinib, a potent inhibitor of KIT activity, is now standard front-line therapy
for advanced GIST. With the introduction of imatinib, there have been dramatic
improvements in response rates, time to progression, and survival. Imatinib is
now being investigated and shows promise in the neoadjuvant and adjuvant
settings. Unfortunately, many patients eventually recur or progress during
imatinib therapy. For these patients, imatinib dose escalation and/or surgical
evaluation are appropriate. Additionally, a novel tyrosine kinase inhibitor such
as SU11248 (sunitinib) is a reasonable option for progressive, imatinib-resistant
disease. With the identification of other downstream pathways, several other
promising therapies are under current investigation either alone or in
combination with imatinib and surgery.
PMID- 17032556
TI - The enigma of desmoid tumors.
AB - Desmoid tumors (aggressive fibromatosis) are rare neoplastic tumors that may
occur sporadically or in association with familial adenomatous polyposis (FAP).
The etiology of these tumors is unknown, but hormonal, genetic, and physical
factors play a role in their development and growth. A distinction is often made
between desmoids in patients with FAP and those in patients without FAP, but
clinically these tumors are treated the same; the only difference is the
preferential intra-abdominal location of FAP desmoids. The goal of desmoid
treatment is local control. Choosing the appropriate method for achieving local
control may be complex as the functional and cosmetic outcomes of each method
must be considered. In addition, because desmoids spontaneously regress, any
claim of successful intervention must be viewed skeptically. Local control is
mainly achieved by surgical intervention and may be improved with the addition of
radiation therapy (RT). For patients who cannot undergo surgery, the options for
local control include RT and systemic therapies such as hormones, nonsteroidal
anti-inflammatory drugs (NSAIDs), interferon, and chemotherapy. Patients with
symptomatic, progressive disease who can tolerate chemotherapy should be
presented with the option of low-dose or standard antisarcoma chemotherapy.
Although it is unclear which regimen is better, patients appear to have quicker
responses to the standard antisarcoma therapy. Hormone therapy, NSAIDs, and
interferon are used often, with varying success, and should be reserved for
minimally symptomatic patients or for patients who do not want or are not
candidates for chemotherapy. The treatment of desmoid tumors remains an enigma.
As more options become available, selecting the correct therapy becomes more
nuanced. Further clinical trials are needed to help the clinician navigate his or
her way through the morass of desmoid tumor therapies.
PMID- 17032557
TI - Management of osteosarcoma.
AB - Improving cure rates for osteosarcoma continues to be a major challenge. The
clinical management of individual patients is exacting and requires a skilled,
experienced team including a surgeon, pathologist, oncologist, and radiologist,
with support from specialist nurses and rehabilitation teams. Outcomes from
treatment have improved little in 20 years and remain disappointing. Chemotherapy
for osteosarcoma is among the most grueling of any given for solid tumors, and
treatment of the primary tumor is associated with permanent disability of some
degree in a significant proportion of patients. New systemic treatments remain
beyond the horizon. In recognition of these difficulties, an international
cooperation has begun with the opening of a randomized trial, European and
American Osteosarcoma (EURAMOS) 1, in Europe and the United States. This study
heralds a new era of clinical investigation into osteosarcoma, with the promise
of valuable biologic insights and rapid evaluation of investigational strategies.
Osteosarcoma should always be treated under the guidance of a specialist team,
and we recommend that whenever possible, patients be offered entry into EURAMOS 1
or other well-designed clinical trials.
PMID- 17032558
TI - Adjuvant therapy for extremity sarcomas.
AB - Extremity soft tissue sarcomas (STS) represent a rare, heterogeneous malignancy.
Surgery is the primary treatment for patients with no evidence of metastatic
disease, and for small low-grade superficial tumors in which adequate margins can
be obtained, it may be the only therapy indicated. For large, deep tumors or
tumors that are close to important neurovascular structures or bone, the addition
of radiotherapy to resection has improved local control and increased limb
salvage without affecting overall survival. Adjuvant chemotherapy has been an
issue of considerable debate. Because 50% of patients with high-risk tumors will
develop metastatic disease, effective systemic treatment with chemotherapy is
needed. Unfortunately, studies have shown minimal improvement in overall survival
when chemotherapy is added to the local treatment of high-risk extremity STS.
More recently, a few trials of neoadjuvant chemotherapy consisting of mesna,
doxorubicin, ifosfamide, and dacarbazine and high-dose doxorubicin and ifosfamide
have shown some early promising results, but at the price of increased toxicity.
Targeted therapy has shown some of its best results with gastrointestinal stromal
tumors, but so far there has been little success in treating extremity STS. At
this time, high-dose adjuvant or neoadjuvant chemotherapy should be given in the
setting of a clinical trial to patients with high-risk tumors who can tolerate a
potentially toxic chemotherapeutic regimen. The goal of these trials should be to
assess new combination therapies, possibly including targeted therapies, for the
management of large high-grade, high-risk soft tissue sarcomas.
PMID- 17032559
TI - Chemotherapeutic options for primary brain tumors.
AB - Malignant gliomas are the most common primary brain tumors. Despite intensive
clinical investigation and many novel therapeutic approaches, treatment for most
primary brain tumors remains inadequate. Most are associated with a high rate of
recurrence after primary therapy and a dismal outcome following recurrence.
Surgery and radiation remain the primary modalities of therapy for malignant
brain tumors. The role of chemotherapy in malignant gliomas, especially
glioblastoma multiforme, has been inconclusive. However, a recent trial by the
European Organisation for Research and Treatment of Cancer and the National
Cancer Institute of Canada combining radiation therapy with temozolomide for
newly diagnosed glioblastoma patients showed a significantly improved survival
benefit over radiation therapy alone. In addition to this encouraging progress,
recent experience has shown that selected malignant brain tumors--for example,
anaplastic oligodendrogliomas, primary central nervous system lymphomas,
medulloblastomas, and intracranial germ cell tumors--are often highly responsive
to chemotherapy. Molecular genetic studies are becoming indispensable aids in the
diagnosis and treatment of the malignant gliomas. For example, we have learned
that allelic loss of chromosome 1p is a significant predictor of
chemosensitivity, whereas combined loss of chromosomes 1p and 19q is a strong
predictor of chemosensitivity, progression-free survival, and overall survival in
patients with anaplastic oligodendroglioma. Similarly, MGMT promoter methylation
is associated with more frequent responses and longer survival in patients with
glioblastoma multiforme receiving temozolomide-based therapy. These and other
recent advances have led to the development and testing of several novel
chemotherapeutic and molecular-targeted agents. Several different approaches and
modalities to improve the efficacy of chemotherapy (eg, MGMT promoter
methylation) are currently under way. Clinical trials implementing angiogenesis
inhibitors, biologic modifiers, or molecular-targeted therapies are also actively
being investigated.
PMID- 17032560
TI - Current therapeutic approaches in patients with brain metastases.
AB - The development of brain metastases is often viewed as the end stage of a disease
course and engenders skepticism about the efficacy of treatment. Aggressive
management of brain metastases is effective in both symptom palliation and the
prolongation of life. The majority of patients with controlled intracranial
metastases will expire from systemic disease rather than from recurrence of these
metastases. Single brain metastases should be treated with surgical resection or
stereotactic radiosurgery, though it is unclear at this time if one modality is
more effective than the other. Surgical resection is preferred when a pathologic
diagnosis is needed, for tumors larger than 3.5 cm, or when immediate tumor mass
decompression is required. Stereotactic radiosurgery (SRS) should be applied for
single tumors less than 3.5 cm in surgically inaccessible areas and for patients
who are not surgical candidates. Small tumors (ie, < 3.5 cm) that cause minimal
edema and are surgically accessible may be treated with either surgery or SRS.
There is controversy over whether whole brain radiation therapy (WBRT) can be
omitted following surgical resection or SRS. Omission of WBRT increases
intracranial tumor recurrence; however, this has not been correlated with
decreased survival. Clinicians who choose to omit upfront WBRT are obligated to
monitor the patient closely for intracranial recurrence, at which time further
salvage therapy in the form of surgery, SRS, or WBRT may be considered. Histology
is of particular importance when considering WBRT for patients with
radioresistant tumors such as melanoma, renal cell carcinoma, or sarcoma. WBRT
may be of less clinical benefit in this setting. Chemotherapy has been
demonstrated to improve response rates when used as an adjunct to radiation
therapy. These improvements in response rates have not been correlated with an
improvement in median survival. Noncytotoxic radiosensitizing agents such as
motexafin and efaproxiral show promise. Phase III trials to assess the benefit of
motexafin in patients with metastatic lung cancer and efaproxiral in patients
with metastatic breast cancer are ongoing. Targeted therapies offer promise in
achieving therapeutic efficacy while minimizing side effects. Surgical adjuncts
such as BCNU (carmustine) wafers and the GliaSite Radiation System (Cytyc
Corporation, Marlborough, MA) may be useful in the future in achieving optimal
local tumor control.
PMID- 17032561
TI - Predictive and prognostic markers in human glioblastomas.
AB - Glioblastomas (GBMs) are among the most aggressive of all known human tumors. The
median survival times remain in the 12- to 15-month range despite aggressive
surgery, radiation, and chemotherapy. Through molecular and genetic profiling
efforts, underlying mechanisms of resistance to these therapies are becoming
better understood. The present standard of care has been shaped by the recently
reported phase III study by the European Organisation for Research and Treatment
of Cancer and the National Cancer Institute of Canada, which found that the
addition of temozolomide (TMZ) to radiation therapy significantly improved
outcome compared with radiation alone. However, careful examination of these data
reveals that not all GBM patients benefited from the addition of TMZ to radiation
therapy. A companion correlative study found that GBM patients with tumors with
MGMT promoter methylation appeared to derive the greatest benefit from the
addition of TMZ to radiation therapy. Although this finding is provocative, it
should be kept in mind that this study was performed retrospectively and that
prospective validation is required before MGMT methylation can be used for
clinical stratification purposes. However, this study does show promise for the
tailoring of future treatments according to the molecular and genetic profiles of
an individual's tumor rather than using the "one-glove-fits-all" approach that is
currently being followed. As more effective "smart drugs" are developed,
molecular and genetic profiling will assume even greater importance in this
regard.
PMID- 17032562
TI - Management of pineal region tumors.
AB - Tumors of the pineal region represent a diverse collection of tumors with a
variety of natural histories. This diversity necessitates accurate histologic
diagnosis to allow rational therapeutic planning. Evaluation of a pineal lesion
should begin with craniospinal MRI and analysis of the cerebrospinal fluid (CSF).
Whereas certainty of the histologic diagnosis is now a requirement for treatment
in Western nations, some Asian centers continue to recommend a test dose of
radiation therapy based on the high incidence of germinoma in those countries. If
there is high clinical suspicion of a germinoma or tectal glioma, stereotactic or
endoscopic biopsy may be pursued. All other lesions should be referred for open
biopsy with microsurgical techniques. This approach provides adequate tissue for
diagnosis, may be curative in low-grade tumors, and may substantially improve
survival in patients with malignant tumors. If open surgery is not desired by the
patient or practitioner, stereotactic or endoscopic biopsy may be followed by
radiosurgery for localized, well-demarcated tumors. Radiation therapy is the
first-line therapy for germinomas. Although the optimal radiation dosage and
volume have not been decided, the current Children's Oncology Group trial may
offer definitive evidence to address this dilemma in germ cell tumors. Evidence
of CSF seeding requires craniospinal radiation and adjuvant chemotherapy
regardless of tumor type. Diagnosis of any of the malignant tumors (non-germ cell
tumors, pineoblastomas, and parenchymal tumors of intermediate determination)
also requires craniospinal radiation (with local tumor doses of at least 50 Gy)
and adjuvant chemotherapy (generally platinum based). Patients with tectal
gliomas may undergo excision with or without postoperative radiation; however,
they also may be observed with vigilant follow-up alone.
PMID- 17032563
TI - Managing the cognitive effects of brain tumor radiation therapy.
AB - Postoperative radiation therapy (RT), either alone or in combination with
chemotherapy, is the mainstay of treatment for primary and/or metastatic brain
tumors. The majority of patients with brain tumors will have significant symptoms
of their disease and of RT that will have a negative impact on their quality of
life and neurocognitive function. The symptoms of brain tumors depend on tumor
location. Radiation-induced brain injury is a complex and dynamic process
involving all cells in the brain, including endothelial and oligodendroglial
cells, astrocytes, microglia, neurons, and neuronal stem cells. The symptoms of
radiation-induced brain injury may be acute, subacute, or chronic, occurring
hours, days, weeks, months, and even years after exposure to radiation, the
pathogenesis of which is oxidative stress and inflammation. At present, there are
no effective preventive approaches for radiation-induced brain injury. Rather,
the management of radiation-induced fatigue, changes in mood, and cognitive
dysfunction involves a multidisciplinary approach using pharmacologic,
behavioral, and rehabilitative therapies. Given the prevalence of brain neoplasms
and the high incidence of the radiation-induced symptom cluster and brain injury,
clinical research to address these important clinical problems is critical.
PMID- 17032564
TI - Diagnosis and treatment of neurotransmitter disorders.
AB - The neurotransmitter disorders represent an enigmatic and enlarging group of
neurometabolic conditions caused by abnormal neurotransmitter metabolism or
transport. A high index of clinical suspicion is important, given the
availability of therapeutic strategies. This article covers disorders of
monoamine (catecholamine and serotonin) synthesis, glycine catabolism, pyridoxine
dependency, and gamma-aminobutyric acid (GABA) metabolism. The technological
aspects of appropriate cerebrospinal fluid (CSF) collection, shipment, study, and
interpretation merit special consideration. Diagnosis of disorders of monoamines
requires analysis of CSF homovanillic acid, 5-hydroxyindoleacetic acid, ortho
methyldopa, BH4, and neopterin. The delineation of new disorders with important
therapeutic implications, such as cerebral folate deficiency and PNPO deficiency,
serves to highlight the value of measuring CSF neurotransmitter precursors and
metabolites. The impressive responsiveness of Segawa fluctuating dystonia to
levodopa is a hallmark feature of previously unrecognized neurologic morbidity
becoming treatable at any age. Aromatic amino acid decarboxylase and tyrosine
hydroxylase deficiency have more severe phenotypes and show variable
responsiveness to levodopa. Glycine encephalopathy usually has a poor outcome;
benzoate therapy may be helpful in less affected cases. Pyridoxine-dependent
seizures are a refractory but treatable group of neonatal and infantile seizures;
rare cases require pyridoxal-5-phosphate. Succinic semialdehyde dehydrogenase
deficiency is relatively common in comparison to the remainder of this group of
disorders. Treatment directed at the metabolic defect with vigabatrin has been
disappointing, and multiple therapies are targeted toward specific but protean
symptoms. Other disorders of GABA metabolism, as is true of the wide spectrum of
neurotransmitter disorders, will require increasing use of CSF analysis for
diagnosis, and ultimately, treatment.
PMID- 17032565
TI - Pediatric headache.
AB - Migraine is very treatable in children and adolescents. Principles of treatment
include early intervention, elimination of triggers, involvement of parents and
schools, and judicious use of medicines. Although there is no pediatric
indication in the United States, triptans are safe and effective in this age
group. Prophylactic drugs should be used when significant disability from
migraine exists. Choice of drug is based upon comorbidity. Nonpharmacologic
treatment has an important role.
PMID- 17032566
TI - Treatment of infantile spasms.
AB - Infantile spasms are associated with a diverse range of conditions, and treatment
options are available. However, outcomes remain generally poor, particularly for
those with symptomatic etiologies. First-line therapy is considered to be
hormonal (adrenocorticotropic hormone; ACTH), which some evidence suggests is
more effective when started early. However, side effects may place limits on its
use acutely and long-term. There is additional evidence for vigabatrin,
specifically for infantile spasms secondary to tuberous sclerosis complex. In
refractory cases, candidacy for surgical management should be explored, along
with new-generation anticonvulsants (eg, topiramate, zonisamide) and the
ketogenic diet. There is urgent need for further treatment trials comparing
anticonvulsants with ACTH and a satisfactory animal model for the study of
spasms.
PMID- 17032567
TI - New treatments for tic disorders.
AB - Tics vary in severity from infrequent and barely noticeable to nearly continuous
and highly disruptive. Treatment of tic disorders depends on the severity of the
tics, the distress they cause, and the effects they have on school, work, or
daily activities. Many tics do not interfere with school or everyday life and do
not require specific treatment. Comorbid disorders such as attention deficit
hyperactivity disorder, anxiety, and obsessive-compulsive disorder occur in more
than 50% of patients. The associated comorbidity can be more bothersome than the
tics themselves. Treatment should be aimed at the most troubling symptom.
Education and reassurance are often sufficient for mild and occasional tics. For
tics of moderate severity, clonidine and guanfacine have a reasonable safety
profile. They are considered as first-line medications. With clonidine, start
with 0.05 mg at bedtime. Increase as needed and as tolerated by 0.05 mg every 4
to 7 days to a maximum dosage of 0.3 to 0.4 mg/day divided three or four times a
day. With guanfacine, start with 0.5 mg at bedtime. The dosage may be increased
as needed and as tolerated by 0.5 mg every week to a maximum dosage of 3 to 4
mg/day, divided twice a day. There are emerging data that behavioral therapy is
effective for treatment of tics in some individuals. Dopamine receptor blockers
are the most potent medications for treating severe tics. The efficacy appears to
be proportionate to the affinity for dopamine D2 receptors. Thus, standard
antipsychotic medications such as haloperidol, pimozide, or fluphenazine are the
most potent. However, these medications commonly cause bothersome side effects.
Therefore, we recommend use of atypical neuroleptics before standard neuroleptics
in most patients. Risperidone is usually the first choice and may have efficacy
for behavior problems that often accompany tics. Start with 0.01 mg/kg/dose once
a day; dosage may be increased by 0.02 mg/kg/day at weekly intervals, up to 0.06
mg/kg/dose once a day. Ziprasidone and olanzapine are reasonable alternatives.
PMID- 17032568
TI - Management of arterial hypertension in patients with acute stroke.
AB - Management of arterial hypertension in the hyperacute period immediately after
stroke ictus remains controversial. Extremes of blood pressure (BP) are
associated with poor outcomes in all stroke subtypes. Severely hypertensive
patients likely benefit from modest BP reductions, but aggressive BP reduction
may worsen outcome. Although little evidence is currently available to
definitively establish guideline recommendations for optimal BP goals at stroke
presentation, recently published research is shedding some light on how to
approach management of BP after stroke. Antihypertensive treatment should
probably be deferred in ischemic stroke patients except in cases of severe
hypertension or when thrombolytic therapy is warranted and the patient's BP is
above acceptable levels. Hypertensive hemorrhagic stroke patients may benefit
from modest BP reductions. Relative hypotension causing regional hypoperfusion is
an increasingly understood concept immediately following ischemic or hemorrhagic
stroke, emphasizing the need for careful titration of appropriate medications to
minimize fluctuations in BP for treated patients. Ongoing trials will improve our
current knowledge regarding BP management after ischemic and hemorrhagic stroke.
PMID- 17032569
TI - Update on the management of hypertension to prevent stroke.
AB - Hypertension is the leading modifiable risk factor for stroke, including first
ever and recurrent stroke. The association between blood pressure (BP) and stroke
risk is continuous and may be documented as low as 115/75 mm Hg. Because of this
continuum of risk, and because most strokes occur in individuals with mild
hypertension or even normal BP values, we are now beginning to recognize
"prehypertension" as a stage in which early recognition and intervention may
confer benefit. In addition to increased risk for ischemic and hemorrhagic
stroke, hypertension may be associated with increased risk of cognitive
impairment. Reductions in BP are reliably associated with reduced stroke risk.
Some evidence suggests that certain agents, including angiotensin-converting
enzyme inhibitors and angiotensin receptor blockers, may have protective effects
beyond BP lowering. Overall, the degree of BP lowering is key, and therefore most
classes of BP-lowering agents may be recommended at this point. Many patients
with hypertension will require more than one BP-lowering agent to control BP.
Lifestyle modification is appropriate at all levels of intervention. Further
studies are needed to ascertain the mechanisms of benefit of different classes of
antihypertensive agents in the reduction of stroke and cardiovascular disease
risk.
PMID- 17032570
TI - Cholesterol lowering to prevent stroke: who, when, and how?
AB - The epidemiologic link between increased low-density-lipoprotein (LDL)
cholesterol and ischemic stroke is controversial. However, recent trials make it
clear that LDL reduction by statin agents in high-risk patients reduces the risk
of ischemic stroke. The risk of first stroke is reduced within 1 to 2 years of
statin therapy in patients at high risk for ischemic vascular disease. Patients
with any history of cerebrovascular disease who are treated with statins have a
reduced risk of coronary ischemic events and of all major vascular ischemic
events, independent of any history of coexisting coronary artery disease. In
particular, patients with recent transient ischemic attack or ischemic stroke
show significantly reduced risks of both recurrent stroke and coronary events
when they are treated with high-dose statin therapy. Most patients with ischemic
cerebrovascular disease should be placed on statin drugs. However, most stroke
patients are not currently treated to recommended levels with these agents,
providing ample room for improvement in physician performance.
PMID- 17032571
TI - Treatment and prevention of stroke in children with sickle cell disease.
AB - Stroke is one of the major complications in children with sickle cell disease
(SCD). Ischemic stroke is associated with small asymptomatic subcortical infarcts
to large territorial lesions causing major disability. Intracranial hemorrhages
may be caused by aneurysm rupture or by leakage from moyamoya vessels or venous
sources. There have been no acute stroke treatment studies in SCD, but hydration
and exchange transfusion are often recommended. However, there is an evidence
base for primary and to some extent secondary stroke prevention. Primary
prevention of stroke was demonstrated in the Stroke Prevention Trial in Sickle
Cell Anemia (STOP), in which children with transcranial Doppler (TCD) mean blood
flow velocities of 200 cm/second (previously shown to indicate high stroke risk)
or higher were randomized to either regular blood transfusions or no transfusion.
The study showed a very significant 90% reduction in first stroke with
transfusion. In STOP2, discontinuing transfusions after 30 months or more (even
with normal TCD) resulted in a high rate of reversion to abnormal TCD values and
stroke. TCD screening of all children with SCD, and initiation and maintenance of
chronic transfusion to maintain hemoglobin S below 30% in the high-risk group, is
the only proven prevention strategy for stroke in SCD. Hydroxyurea is being
studied as secondary stroke prevention at this time. No recommendation specific
to SCD regarding the use of antiplatelet agents or anticoagulants in ischemic
stroke can be made. Bone marrow transplantation can be curative for SCD, and
limited data support its use to prevent stroke in SCD.
PMID- 17032572
TI - Interactions between migraine and stroke.
AB - When a patient with migraine has a stroke, all other causes of stroke should be
ruled out before the stroke is attributed to migraine. Migraine mimics that
present with headaches and stroke, including arteriovenous malformation and
cervical carotid artery dissection, should be considered. Patent foramen ovale is
a risk factor for both migraine and stroke and should be ruled out with
transesophageal echocardiography. A patient with migraine with aura with
persistent focal neurologic deficits in the distribution of the typical aura can
be diagnosed with migrainous stroke. Patients with migraine with aura with
persistent focal neurologic deficits can be treated pharmacologically with
intravenous verapamil or magnesium sulfate to relieve the symptoms in familial
hemiplegic migraine and sporadic hemiplegic migraine. Prophylactic treatment
should be administered to patients with frequent attacks of migraine with aura to
prevent recurrence. Oral verapamil is recommended for patients with familial
hemiplegic migraine and may be effective in patients with sporadic hemiplegic
migraine. Endovascular closure of patent foramen ovale has been reported to
prevent recurrence of migraine with aura. The role of patent foramen ovale
closure remains controversial pending completion of controlled randomized trials.
PMID- 17032573
TI - Evolving trends in medical care-coordination for patients with HIV and AIDS.
AB - HIV/AIDS is a condition characterized by a variety of medical and social needs
that affect individuals over time. System-level problems of access, rising costs
of care, and varying quality of HIV/AIDS care in addition to the individual
barriers to care such as stigma, perceived discrimination, competing needs, and
co-morbid conditions have highlighted the importance of using comprehensive
approaches to care delivery. Several types of services have been proposed to
improve care coordination for various diseases, including case management,
community health workers, promotoras, and patient navigators. In this paper, we
will review the characteristics of care coordination interventions for persons
with HIV and the findings in the literature about their association with HIV
health outcomes. We will conclude with a discussion of the implications and
important areas for further investigations on this topic.
PMID- 17032574
TI - Contingency management interventions for HIV-related behaviors.
AB - Contingency management (CM) is a scientifically based treatment approach
typically employed in substance abuse treatment settings to reinforce drug
abstinence, counseling attendance, completion of activities, or other treatment
goals. Although the application of CM to HIV management has few published
studies, it shows promise as an intervention for HIV-related behaviors. CM
interventions such as voucher reinforcement, prize systems, and cash incentives
can be used to reduce HIV risk behaviors and to improve HIV medication adherence.
CM programs have wide applicability to HIV prevention and management in clinical
and community settings and can be implemented as stand-alone techniques or in
combination with other interventions.
PMID- 17032575
TI - Approaching "HIV elimination": interventions for acute HIV infection.
AB - Recent observations from several groups suggest that individuals with acute
(antibody negative) HIV infections (AHI) may present for "routine" HIV testing in
unanticipated numbers. Most of these papers have highlighted the use of group
testing strategies to screen antibody negative testing sera for HIV RNA using
nucleic acid amplification tests. At the same time, accumulating evidence
indicates that AHI is a time of briefly, but substantially elevated risk for
transmission of HIV. In this paper, we review these new data with attention to
their implications for HIV prevention strategies. By calling attention to a
subset of patients that are both recently infected and at transiently very high
risk of transmitting their new infection to partners, AHI detection makes it
possible to use traditional, network notification-based public health strategies
effectively in the fight against HIV.
PMID- 17032576
TI - Rapid HIV testing: a review of the literature and implications for the clinician.
AB - HIV counseling and testing services are critical for individuals to access HIV
prevention and treatment. Unfortunately, the standard HIV testing algorithm is
complex and includes the use of a sensitive enzyme immunoassay (EIA), followed by
a Western blot if the EIA is positive. This process can take 1 week or longer.
Therefore, innovative approaches that incorporate simpler diagnostic algorithms
are needed to reach the large number of individuals who are not aware that they
are HIV-infected. Currently available rapid HIV tests have demonstrated
sensitivities and specificities comparable to those of standard HIV testing
without the requirements of sophisticated laboratory resources or highly trained
personnel. These rapid HIV tests are increasingly being used in various clinical
scenarios to decrease the number of missed opportunities for detection of HIV
infection. Their use is particularly applicable in specific clinical and
nonclinical settings; public health settings; labor and delivery wards; in the
management of occupational exposures; and in resource-constrained settings. The
overarching goals of achieving wide implementation of rapid HIV tests are to
increase the number of individuals who are aware of their serostatus, to improve
entry of persons with HIV into prevention and care services, and to prevent
further HIV transmission.
PMID- 17032577
TI - Psychiatric behavioral aspects of comanagement of hepatitis C virus and HIV.
AB - Coinfection with HIV hastens the progression of liver disease in persons with
hepatitis C virus (HCV) infection. As mortality directly due to HIV continues to
decrease among persons who are HIV-positive, coinfection with HCV has emerged as
a leading cause of death. There is increasing attention to the need to actively
treat HCV infection in HIV/HCV coinfected patients. Current HCV treatment with
pegylated interferon and ribavirin achieves sustained viral response in up to 40%
of coinfected patients but has numerous neuropsychiatric side effects. Providers
are hesitant to begin HCV treatment in the coinfected population given the high
prevalence of existing psychiatric illness, cognitive impairment, and substance
use disorders. There is an urgent need for research into the psychiatric and
behavioral predictors of HCV treatment adherence and virologic outcome, as well
as into the optimal psychiatric management of the neuropsychiatric sequelae of
HCV therapy.
PMID- 17032578
TI - Extending HIV care in resource-limited settings.
AB - Despite the clear benefits of antiretroviral therapy (ART), only three countries
in sub-Saharan Africa have achieved the "3 by 5" goal of treating at least half
of the persons living with HIV/AIDS who need it. A major obstacle faced by many
lower income countries is the establishment of treatment programs in rural areas
where there is a scarcity of trained health care providers and infrastructure.
This paper reviews published data on rural ART programs in lower income countries
to identify necessary components of such a program. No clearly superior model for
rural ART delivery has emerged. All programs document the need for expanded
physical infrastructure, laboratory development, recruitment/training of
additional health care providers, and/or the introduction of new technologies in
order to effectively support the needs of ART roll-out.
PMID- 17032580
TI - Society for Reproductive Biology Founders' Lecture 2006 - life in the pouch: womb
with a view.
AB - Marsupials give birth to an undeveloped altricial young after a relatively short
gestation period, but have a long and sophisticated lactation with the young
usually developing in a pouch. Their viviparous mode of reproduction trades
placentation for lactation, exchanging the umbilical cord for the teat. The
special adaptations that marsupials have developed provide us with unique
insights into the evolution of all mammalian reproduction. Marsupials hold many
mammalian reproductive 'records', for example they have the shortest known
gestation but the longest embryonic diapause, the smallest neonate but the
longest sperm. They have contributed to our knowledge of many mammalian
reproductive events including embryonic diapause and development, birth
behaviour, sex determination, sexual differentiation, lactation and seasonal
breeding. Because marsupials have been genetically isolated from eutherian
mammals for over 125 million years, sequencing of the genome of two marsupial
species has made comparative genomic biology an exciting and important new area
of investigation. This review will show how the study of marsupials has widened
our understanding of mammalian reproduction and development, highlighting some
mechanisms that are so fundamental that they are shared by all today's marsupial
and eutherian mammals.
PMID- 17032581
TI - Reproduction in female swamp wallabies, Wallabia bicolor.
AB - The swamp wallaby (Wallabia bicolor) is a common, medium-sized, browsing
macropodid marsupial that is unique in many ways. Relatively little is known
about the reproductive biology of this species. Previous studies have proposed
that the swamp wallaby has a pre-partum oestrus because the gestation period (x =
35.5 days, n = 4) is on average longer than the oestrus period (x = 31.0 days, n
= 5) and the period from the removal of pouch young (RPY) to mating (x = 26.0
days, n = 3). In the current study, the period from RPY to birth was confirmed at
x = 31.25 days (n = 4) in captive animals, consistent with a pre-partum oestrus.
A growth curve for swamp wallaby pouch young was constructed from the progeny of
captive animals to estimate the age and date of birth of young in a wild, culled
population in South Gippsland, Victoria, and the reproduction of females in the
wild throughout the year was examined. Young were born in every month of the
year, with no statistically significant variation in the number of young born in
each month. Females did not have a period of seasonal anoestrus and conceived
throughout the year. Female swamp wallabies in South Gippsland bred continuously
throughout the period of this study.
PMID- 17032579
TI - The potential impact of antiretroviral therapy on fertility in sub-Saharan
Africa.
AB - Approximately 14 million women of child-bearing age are living with HIV/AIDS in
sub-Saharan Africa. Women with HIV infection have between 25% and 40% lower
fertility than noninfected women. As antiretroviral (ARV) therapy becomes
increasingly accessible in sub-Saharan Africa, it is important to understand
whether and how the associated clinical improvements correspond with changes in
the incidence of pregnancy and fertility. Accordingly, this paper reviews the
literature on the potential impact of ARV therapy on the fertility of women with
HIV infection in sub-Saharan Africa. We use Bongaarts' proximate determinants of
fertility framework (adapted for conditions of a generalized HIV epidemic) to
examine the underlying mechanisms through which use of ARV therapy may impact the
fertility of women with HIV infection. A conceptual framework is proposed to
guide future research aimed at understanding how widespread use of ARV therapy
may impact fertility in sub-Saharan Africa.
PMID- 17032582
TI - Oestrous behaviour and development of preovulatory follicles in goats induced to
ovulate using the male effect with and without progesterone priming.
AB - The objective of the current study was to examine follicular dynamics in goats
induced to ovulate by using the male effect with or without progesterone
pretreatment. Ten Murcian-Granadina goats were treated with a single dose of 25
mg of progesterone in olive oil on the day of male effect induction (Day 0),
whereas ten does remained untreated. Changes in the ovarian follicular population
and onset of oestrous behaviour were checked daily from Day 0 to the day on which
ovulation was detected by ultrasonography. All of the treated goats and only 20%
of control goats (P < 0.001) showed oestrous behaviour between 72 and 96 h after
the introduction of bucks. Differences in follicle growth were found between the
groups. The control goats exhibiting oestrous behaviour during the first 4 days
of ovarian screening and all of the goats treated with progesterone had their
preovulatory follicles in growing phase. However, the largest follicles in
control does not showing oestrus in these first 4 days were in regressing phase,
being necessary for the emergence of new preovulatory follicles from a new
follicular wave between Days 6 and 7, for exhibition of oestrous behaviour and
subsequent ovulation. In conclusion, the appearance of short luteal phases and
delayed ovulation in goats treated with the male effect during seasonal
anoestrous depends on the stage of follicle development at the time of buck
introduction. A single injection of progesterone stimulates the emergence of a
new follicular wave, able to grow and give adequate ovulation after induction of
the male effect.
PMID- 17032583
TI - Similarities between female meadow voles mating during post-partum oestrus and
raising two concurrent litters and females raising only one litter.
AB - In many species of small mammals, females undergo post-partum oestrus soon after
delivering a litter, becoming pregnant while suckling the previous litter.
Females raising two concurrent litters need to allocate many more resources to
reproduction than females raising only one litter. Consequently, there may be
differences between litters raised concurrently or singly. We investigated this
issue in the meadow vole, Microtus pennsylvanicus, a species in which most
females in the wild reproduce during post-partum oestrus. Specifically, we tested
the hypothesis that the development of pups in two concurrent litters differs
from that of pups in a single litter. To test this hypothesis, we measured the
following variables for concurrent and singly reared litters: gestation length;
litter size; sex ratio; bodyweight of males and females at different ages; total
litter weight at weaning; growth rates; and intra-litter variation in body mass.
Except for bodyweight of males at 60 days of age, which was higher in the first
of the concurrent litters, none of the variables differed among the litters.
These results indicate that females are able to adjust to differing loads of
maternal care to provide equivalent resources to concurrent litters and singly
reared litters.
PMID- 17032584
TI - Regulation of protein tyrosine phosphatase 4a1, B-cell translocation gene 2,
nuclear receptor subfamily 4a1 and diacylglycerol O-acyltransferase 1 by follicle
stimulating hormone in the rat ovary.
AB - Ovarian response to follicle stimulating hormone (FSH) and luteinising hormone
(LH) leads to the formation of a mature follicle that is eventually ovulated. FSH
and LH are essential for this process because they direct changes in somatic
cells associated with folliculogenesis by regulating the expression of multiple
genes. We hypothesised that genes induced by FSH in rat Sertoli cells would also
show hormonal regulation during rat folliculogenesis. The objective of this study
was to determine the expression patterns of diacylglycerol O-acyltransferase 1
(Dgat1), nuclear receptor subfamily 4a1 (Nr4a1), an anti-proliferative gene
(Btg2) and a protein tyrosine phosphatase (Ptp4a1) in the ovaries of pregnant
mare serum gonadotrophin (PMSG)-treated and human chorionic gonadotrophin (hCG)
treated rats. Expression of Dgat1, Nr4a1 and Ptp4a1 was induced in ovaries 4 h
post PMSG treatment. When rats were treated with hCG, Dgat1, Nr4a1 and Ptp4a1
expression was induced by 12 h. Expression of Nr4a1 protein increases 12-24 h
after induction of gene expression. Nr4a1 protein was observed in the granulosa,
theca and luteal cells post PMSG and hCG treatment. These findings should
increase our knowledge of mechanisms regulating folliculogenesis and
luteinisation and demonstrate the diverse proteins that are important in ovarian
function.
PMID- 17032585
TI - Giant panda (Ailuropoda melanoleuca) spermatozoon decondensation in vitro is not
compromised by cryopreservation.
AB - Natural breeding of giant pandas in captivity is compromised, making artificial
insemination and spermatozoa cryopreservation essential for genetic management.
This study examined the influence of freeze-thawing on traditional parameters
such as motility and spermatozoon functionality, specifically decondensation in
vitro. Giant panda spermatozoa were assessed before and after rapid
cryopreservation (4 degrees C to -130 degrees C over 2 min) in liquid nitrogen
vapour. Spermatozoa pre-incubated in medium for 6 h were co-incubated with cat
zonae (2 zonae microL(-1)) for 30 min to effect capacitation and an acrosome
reaction. Spermatozoa were then mixed with mature cat oocyte cytoplasm (2
cytoplasm microL(-1)) for 4 h and evaluated for decondensation. Frozen
spermatozoa were less motile (P < 0.05) than fresh counterparts immediately post
thawing, but not after 6 h incubation. There were more (P < 0.05) spermatozoa
with completely diffused chromatin post-thaw (10.4 +/- 1.3%; mean +/- s.e.m.)
compared to fresh counterparts (5.1 +/- 1.0%). However, there was no overall
difference (P > 0.05) in the incidence of decondensation between fresh (4 h, 69.8
+/- 5.9%) and thawed (4 h, 71.5 +/- 4.9%) spermatozoa after exposure to cat
oocyte cytoplasm. It is concluded that the 'rapid' method now used to
cryopreserve giant panda spermatozoa has little impact on spermatozoon
decondensation.
PMID- 17032586
TI - Comparison of protocols for cryopreservation of rhesus monkey spermatozoa by post
thaw motility recovery and hyperactivation.
AB - Cryopreservation of spermatozoa is useful for gene banking and for in vitro
fertilisation (IVF). This study compared several published cryopreservation
techniques to find the most efficient for rhesus macaques. Effectiveness was
assessed by sperm longevity (post-thaw motility % and duration) and ability to
hyperactivate in response to chemical activators (caffeine, dibutyryl cyclic
AMP). Each ejaculate from three males was treated with four published
cryopreservation protocols (Seier et al. 1993; Sanchez-Partida et al. 2000; Si et
al. 2000; Isachenko et al. 2005). Upon thawing, each sub-sample was incubated
either at 37 degrees C in 5% CO2 in air with or without activators or at
approximately 22 degrees C in atmospheric air without activators for 0-24 h.
Samples cryopreserved using one method showed zero motility and were not included
in the 2 ;2 G-test statistical analysis. The other methods all demonstrated good
immediate post-thaw motility rates (68%, 73% and 62% respectively) and underwent
capacitation after exposure to activators. Sperm motility in each treatment
decreased over time at both temperatures but overall, incubation at 22 degrees C
preserved motility better in all three methods. In summary, cryopreservation of
rhesus spermatozoa using the method published by Sanchez-Partida et al. or Seier
et al. appeared best, potentially supporting gene banking as well as allowing for
multiple IVF uses from the same sample.
PMID- 17032587
TI - Sperm DNA damage is related to field fertility of semen from young Norwegian Red
bulls.
AB - Flow cytometry was utilised for the first time to independently measure five
sperm parameters of individual spermatozoa of bull ejaculates to differentiate
between outcome successes after artificial insemination (AI). These parameters
included plasma membrane and acrosome integrity, mitochondrial functionality and
DNA damage measured by sperm chromatin structure assay (SCSA) and terminal
deoxynucleotide transferase-mediated dUTP nick end labelling (TUNEL) assays. For
each parameter, results of 142 ejaculates (30 bulls) were ranked into three
groups according to their flow cytometric measures: (1) ejaculates with the 25%
lowest measures; (2) the 50% middle measures; and (3) the 25% highest measures.
In total, 20 272 first-service inseminations (18 ;10(6) spermatozoa per AI dose)
were performed, where fertility was defined as non-return within 60 days after
first insemination. While plasma membrane and acrosome integrity, and
mitochondrial functionality were not significantly related to fertility, data
from SCSA and TUNEL assays were significantly associated with fertility.
Ejaculates in SCSA group 1 had higher odds of AI success (1.07, 95% CI = 1.02
1.12), whereas those in group 3 had lower odds of AI success (0.94, 95% CI = 0.89
0.99), compared with the average odds of all three groups. Ejaculates in group 2
did not have significantly higher odds of AI success compared with the average
odds. For TUNEL-positive spermatozoa, the odds of AI success was higher in group
1 compared with the average odds (1.10, 95% CI = 1.02-1.13), whereas odds of AI
success in groups 2 and 3 were not significant compared with the average odds. In
conclusion, despite the high number of spermatozoa per AI dose from high-quality
bulls, both SCSA and TUNEL assays were valuable measures in this study for
evaluating sperm quality in relation to fertility after AI.
PMID- 17032588
TI - Effects of amino acid supplements and replacement of polyvinyl alcohol with
bovine serum albumin in porcine zygote medium.
AB - The effects of glutamine, hypotaurine, taurine and premixed solutions of
essential amino acids (EAA) and non-essential amino acids (NEAA) on in vitro
development of porcine zygotes were evaluated. The effects of refreshing the
medium and replacing polyvinyl alcohol (PVA) with bovine serum albumin (BSA) on
embryonic development were also investigated. Porcine zygotes produced by in
vitro maturation (IVM) and in vitro fertilisation (IVF) were cultured in porcine
zygote medium (PZM), as the basal culture medium, for 5 days after IVF. The total
number of cells in blastocysts was significantly increased by the addition of 2
mm glutamine to PZM, as was blastocyst yields after supplementation with 0.25 to
4 mm glutamine. Addition of 1.25 to 10 mm hypotaurine to PZM significantly
increased blastocyst yields. Addition of 5 mm taurine to PZM significantly
increased blastocyst yield, whereas taurine had no effect on blastocyst yield in
cultures already containing 5 mm hypotaurine. Adding 1 x EAA significantly
increased the rate of blastocyst formation compared with no or 2 x EAA, whereas 2
x NEAA significantly increased the total cell numbers in blastocysts compared
with no NEAA. Refreshing the medium at Day 3 had no effect on blastocyst yields,
whereas medium change significantly reduced the total cell numbers in
blastocysts. Adjusting the amino acid concentrations of a chemically defined
medium can improve the developmental competence of porcine embryo.
PMID- 17032589
TI - Variation of sperm head shape and tail length in a species of Australian
hydromyine rodent: the spinifex hopping mouse, Notomys alexis.
AB - In Australia, there are around 60 species of murid rodents that occur in the
subfamily Hydromyinae, most of which produce highly complex, monomorphic,
spermatozoa in which the head has an apical hook together with two ventral
processes containing filamentous actin and a long tail of species-specific
length. One of the few exceptions to this is the spinifex hopping mouse, Notomys
alexis, whose spermatozoa have previously been shown to have pleiomorphic heads.
In this study, the structural organisation of the sperm head has been
investigated in more detail and the variability in length of the midpiece and
total length of the sperm tail has been determined for this species. The findings
confirm that pleiomorphic sperm heads are invariably present in these animals and
that this variability is associated with that of the nucleus, although nuclear
vacuoles were not evident. The total length of the sperm tail, as well as that of
the midpiece, was also highly variable both within, as well as between,
individual animals. The reason(s) for this high degree of variability in sperm
morphology is not known but it may relate to a relaxation of the genetic control
of sperm form owing to depressed levels of inter-male sperm competition.
PMID- 17032590
TI - [Not just another kinase. New knowledge about myeloproliferative disease].
PMID- 17032591
TI - [New molecular markers within the chronic myeloproliferative disorders. I: the
PRV-1 gene].
AB - PRV-1 is a new molecular marker within the Ph-negative chronic myeloproliferative
disorders. PRV-1 is a useful, highly sensitive and specific marker in the
differentiation between polycythaemia vera (PV) and secondary erythrocytosis
(ET), and seems to identify those PV patients presenting in the early phase of
the disease with dominating thrombocytosis and thus a clinical phenotype of ET.
These PRV-1 positive ET patients can be regarded as having "masked" PV or, more
accurately, as having early PV. Moreover, PRV-1 positivity may be associated with
a particular risk of thromboembolic complications. The biological role of PRV-1
and the significance of alterations in PRV-1 gene expression levels during
treatment remain to be clarified.
PMID- 17032592
TI - [New molecular markers within the chronic myeloproliferative disorders. II: the
JAK2 mutation].
AB - The Philadelphia-negative chronic myeloproliferative disorders feature autonomous
myeloid hyperproliferation and hypersensitivity to a number of growth factors,
which most recently have been shown to be explained by a guanine-to-thymidine
mutation in the Janus tyrosine kinase (JAK2) gene, implicating that phenylalanine
is substituted with valine in position 617 (V617F mutation). JAK2 is of
particular importance to haematopoiesis, since JAK2 proteins are activated mainly
by the haematopoietic growth factors. The JAK2 mutation is present in most
patients with polycythaemia vera and about 50% of patients with essential
thrombocytosis and idiopathic myelofibrosis. The identification of the JAK2
mutation is a major molecular breakthrough in the understanding of the
pathobiology of these disorders, and it is a new molecular marker to be used in
the future classification of the diseases as well as a simple and rapid
diagnostic test. The mutated JAK2 tyrosine kinase is an obvious potential target
for a small-molecule inhibitor of tyrosine kinase activity.
PMID- 17032593
TI - [Chronic inflammation increases the risk of cardiovascular disease in patients
with rheumatoid arthritis].
AB - Rheumatoid arthritis is associated with increased cardiovascular morbidity and
mortality due to atherosclerosis. This cannot be explained by an increased
presence of traditional risk factors but seems to depend on inflammatory
mechanisms. The association of inflammatory pathways with atherosclerosis is
complex, and more research is required to optimise preventative measures against
cardiovascular complications in inflammatory rheumatic diseases.
PMID- 17032594
TI - [Colorectal foreign bodies].
AB - A patient with a retained anally introduced colorectal foreign body or
complications hereof needs appropriate treatment. The patient may be in danger
and is certainly in discomfort. The problem is relatively rare; however, its
incidence may be expected to increase. Guidelines for handling of the situation
are lacking in many textbooks. Here, a suggestion for handling of a patient with
a retained colorectal foreign body or complications hereof is presented.
PMID- 17032595
TI - [Selenium and health].
AB - Selenium is an essential micronutrient. The average selenium intake in Danish
adults is close to the recommended level of 40-50 mg/day. There is no scientific
documentation showing that an increased selenium intake will result in disease
prevention. However, a preventive effect on some cancers and hearth disease
cannot be ruled out. Fortification of foods via increased selenium content in
fertilizers is a possible way of increasing selenium intake. The tolerable upper
intake level of 60 mg/day in children 1-3 years old must not be exceeded, which
makes fortification difficult.
PMID- 17032596
TI - [Tibialis posterior tendon dysfunction. An often neglected cause of painful adult
flatfoot].
AB - The posterior tibialis tendon is the most important dynamic stabilizer of the
medial longitudinal arch of the foot. Posterior tibial tendon dysfunction (PTTD)
may result from an acute trauma or a progressive degeneration of the tendon and
should be suspected in painful flatfoot. The diagnosis is largely clinical, based
on pain, tenderness and swelling along the tendon underneath the medial
malleolus, the too-many-toes sign and persistant hindfoot valgus during heel
rise. Untreated PTTD often results in total collapse of the longitudinal arch and
severe osteoarthritis of the ankle or hindfoot. In traumatic cases acute repair
of the tendon should be considered.
PMID- 17032597
TI - [Alcohol consumption by middle-aged and elderly Danes from 1987 to 2003].
AB - INTRODUCTION: The trend in alcohol consumption by middle-aged and elderly Danes
has received little attention, but earlier studies indicated increased
consumption. Social factors may influence the trend. Our objective was to
investigate the trend in alcohol consumption by the middle-aged and elderly and
inquire about significant trends among specific social subgroups. MATERIALS AND
METHODS: In the Danish Health and Morbidity Survey carried out in 1987, 1994,
2000 and 2003, a total of 11,754 people aged 50 and older were asked about their
alcohol consumption. The mean alcohol intake and the number of heavy drinkers
were compared from year to year. RESULTS: The mean intake per day increased from
1.5 drinks in 1987 to 2.1 drinks in 2003 for men and from 0.5 drink in 1987 to
1.0 drink in 2003 for women. The percentage of elderly drinking above the
sensible drinking limits increased from 15.2% to 20.4% for men and from 10.7% to
13.6% for women. The strongest increasing trend in the number of heavy drinkers
was in the lowest socio-economic groups and among those married or cohabiting.
CONCLUSION: The increased number of heavy drinkers among the middle-aged and
elderly is of great importance to their general state of health. The increase has
possibly been caused by a social and cultural development which has led to a
generation of elderly who used to drink alcohol earlier in their lives and
continue drinking in old age. More focus on alcohol consumption among the middle
aged and elderly in health policy initiatives is needed.
PMID- 17032598
TI - [Patients' satisfaction with the Mobile Emergency Care Unit in Copenhagen].
AB - INTRODUCTION: Patients' satisfaction with physician-staffed ambulances in
Copenhagen had not previously been investigated. We therefore conducted a survey
of patients' satisfaction with the Mobile Emergency Care Unit (MECU) in
Copenhagen. MATERIALS AND METHODS: The period of investigation was from 1
September 2003 to 31 December 2003. Patients with a diagnosis of COPD, asthma or
a cardiac disease were eligible for inclusion. Patients were excluded if they had
not yet been discharged from hospital, were registered as deceased, were under
the age of 18, were without a known address or had previously been included.
RESULTS: During the period of investigation, 282 questionnaires were sent out;
225 were returned, for a response rate of 80%. The patients' mean age was 71 (18
99 years). On the part of 96% of the patients, the general impression of the MECU
was very good or good, and 85% felt more confident when being treated by a
physician in addition to the regular ambulance crew. The majority (80%) felt that
the information given by the physician had been good, and 90% that the conduct of
the physician had been satisfactory or better. In 11 questionnaires the patients,
in their own words, described dissatisfaction with part of the MECU. In seven
cases this concerned the conduct of or the information given by the ambulance
crew. Most of the patients and physicians felt that the efforts of the MECU had
improved the patient's condition. CONCLUSION: We conclude that in general
patients are satisfied with the service provided by the MECU. They are aware of,
and feel more confident when being treated by, a physician in addition to the
regular ambulance crew. Reasons for dissatisfaction were the conduct of and the
information given by the physician.
PMID- 17032599
TI - [Fatal cases of poisoning in eastern Denmark during a five-year period (1998
2002)].
AB - INTRODUCTION: The goal of this investigation was to determine the pattern of
fatal poisonings in eastern Denmark from 1998 to 2002 and compare it with similar
investigations from 1979 to 1996. MATERIALS AND METHODS: The material included
2,996 autopsies from eastern Denmark in which extensive forensic chemical
investigations were performed. RESULTS: Of the 2,996 autopsies, 694 cases were
drug addicts, in whom 497 fatal overdoses were detected, while in the remaining
2,302 cases of nonaddicts, 443 fatal poisonings were determined. Morphine
(heroine) and methadone were the main causes of death among the fatal poisonings
of the drug addicts, accounting for 90% of the cases. The fatal poisonings among
the nonaddicts were due mainly to medicine (73% of the cases); 13% were due to
carbon monoxide and/or cyanide poisoning, and 12% were due to acute ethanol
poisoning. The medicine was a wide range of strong and weak analgesics,
antidepressants and antipsychotic drugs of older and newer origins. Comparison
with earlier investigations from 1979 to 1996 showed that the poisoning pattern
had changed, but similarities were also seen. The most frequently occurring drugs
involved in fatal poisonings in eastern Denmark from 1979 to 2002 were morphine,
methadone, ethanol and carbon monoxide/cyanide, of which methadone increased in
occurrence over the 23-year period. CONCLUSION: The investigation of fatal
poisonings is an important element in monitoring changes in drug abuse and
poisoning patterns and levels.
PMID- 17032600
TI - [Life-threatening liver failure and severe dyscrasias in blood and lymph nodes
caused by sulphasalazine].
AB - We report a case of sulphasalazine-related drug-induced hypersensitivity syndrome
(the "three-week sulphasalazine syndrome") in which periferal T-cell lymphoma was
a provisory diagnosis. A 40-year-old woman with seropositive rheumatoid arthritis
was admitted to a local hospital 26 days after initiation of sulphasalazine
treatment. She had fever, lymphadenopathy, dermatitis and facial oedema and
showed biochemical signs of progressive hepatitis. Peripheral blood counts showed
elevated leucocyte count with 15% atypical plasmacytes. Lymph node biopsy showed
altered follicular architecture, a diffuse CD 4 positive predominance and
histiocytes with erythrophagocytosis. Investigation by gene rearrangement for
clonality of B- and T-lymphocytes ruled out the suspicion of lymphoma.
Haematological and near-fatal hepatological changes resolved following
discontinuation of sulphasalazine and a three-week course of glucocorticoid
therapy. Early awareness of this syndrome via measuring liver function tests on,
e.g., days 14-35 in patients started on sulphasalazine is recommended.
PMID- 17032602
TI - [100 years with Alzheimer disease].
PMID- 17032603
TI - [Lifestyle-related risk factors for dementia].
AB - Emerging knowledge about modifiable risk factors for dementia has given rise to
interventions that can potentially prevent or delay the onset of dementia and the
possible target periods for intervention extend from prenatal period to old age.
Factors during early life such as nutrition, education, and parental
socioeconomic status can influence the development of dementia later in life.
From mid to late life, a physically, socially, and intellectually active
lifestyle is associated with reduced risk for dementia. Moreover, modification of
cardiovascular risk factors during this period can potentially reduce risk for
dementia.
PMID- 17032604
TI - [Dementia--genetic aspects].
AB - Several prevalent, sporadic neurodegenerative disorders also occur as rare
inherited variants. Mapping of the genes involved in rare variants of the
disorders has contributed to elucidating pathogenetic pathways for several
dementia disorders, and the increased knowledge creates a possibility for
development of new molecular genetic methods for diagnostics and for the
treatment of the different types of dementia. Although inherited dementia
disorders are generally rare, a genetic basis should always be considered when
facing a patient with a recently clinically diagnosed dementia disorder.
PMID- 17032605
TI - [Depression and the risk of Alzheimer's disease].
AB - A population based cohort study consisting of 3346 participants aged 65-84 years
was examined at baseline (1992-94) and after two and five years. The purpose was
to examine whether a history of depression increased the risk of Alzheimer's
disease (AD). History of depression was based on self-report and AD was diagnosed
according to NINCDS-ADRDA. Logistic regression was used to calculate the odds
ratio (OR (95% confidence interval)). Subjects with a history of depression had
an increased risk of AD: Baseline (OR = 1,7 (1,0-2,7)); after two years (1,9 (1,0
3,3)); after five years (1,6 (0,9-2,7)).
PMID- 17032606
TI - [Screening and case finding instruments for depression--results from a Cochrane
review].
PMID- 17032607
TI - [Diagnostic imaging in dementia evaluation].
AB - INTRODUCTION: The aim of the study was to evaluate the changes in diagnoses and
treatment by structural scanning in dementia evaluation. MATERIAL AND METHODS:
336 elderly, consecutively evaluated patients from two university memory clinics
(mean age 75 y, mean MMSE 21.7), were retrospectively diagnosed without and with
inclusion of scan results. These results were compared to prospective data
obtained from 137 patients scanned as part of a population based study (The
Odense Study, mean age 78.5, mean MMSE 23.3). CT and MRI were performed in 93%
and 7% of the patients, respectively. RESULTS: Potentially reversible structural
pathology was found in 3.5% of the memory clinic patients, and in 2% of the
population based patients. By applying international diagnostic criteria and
treatment recommendations to the retrospective memory clinic data, it was found
that adding a structural scan changed diagnoses and treatment in 37% and 33% of
the patients, primarily due to identification of cerebrovascular disease (CVD) in
patients with no clinical signs or symptoms of CVD. In comparison, the change in
diagnosis found in the prospective population data was lower (15%). It was not
possible to identify a group of patients that would not benefit from scanning.
CONCLUSION: Our data support recent guidelines that suggest CT scan as a routine
investigation in dementia evaluation.
PMID- 17032608
TI - [Memory problems among elderly patients in general practice: the importance of
caregiver information].
AB - INTRODUCTION: The aim was to describe and analyse signs that make caregivers
suspect memory problems among elderly patients in general practice. METHODS: This
prospective study was conducted in October and November 2002 among all patients
aged 65 or older who consulted a GP in a total of 17 practices in Copenhagen
inner city. The patients who agreed to participate were asked to complete a
questionnaire regarding memory, quality of life, etc. Their GP completed a
questionnaire independently, and a MMSE was subsequently given to the patient.
Where consent was obtained from a patient, a postal questionnaire regarding the
patient's memory was mailed to a caregiver chosen by the patient. RESULTS: Out of
775 patients 62% (483) gave consent to contact a caregiver. Among the caregivers
who received the questionnaire a total of 74% returned the questionnaire. A total
of 88 (26%) of the caregivers suspected that the patient had memory problems.
Predictors for caregiver suspicion of memory problems were: patient had
complained about memory problems to caregiver (OR 21.7), caregiver had received
information for other sources that the patient suffered from memory problems (OR
5.0), a MMSE in the interval between 0-24 (OR 4.5) and a low quality of life (OR
3.1). Furthermore, if the patient was male, caregivers were more likely to report
memory problems. CONCLUSION: Memory impairment is commonly observed by
caregivers, but is rarely discussed with a GP. The results indicate that more
focus on the possibility of memory impairment among elderly patients is important
in general practice.
PMID- 17032609
TI - [Medical treatment of Alzheimer's disease].
AB - In Denmark, Alzheimer drugs have been registered since 1997. Three cholinesterase
inhibitors (donepezil, rivastigmin og galantamin) are approved mild to moderate
Alzheimer's disease and one partial NMDA receptor antagonist (memantin) with the
indication moderate to severe Alzheimer's disease. The treatment is symptomatic
with a parallel shift of the course. The life expectancy does not seem to be
altered. There is documented effect on the cholinesterase inhibitors of up to two
years and for memantine for 6 months. New disease modifying agents are under
clinical development.
PMID- 17032610
TI - [Psychopharmacological treatment of behavioral and psychological symptoms in
dementia].
AB - Behavioural and psychological symptoms of dementia (BPSD) are common and can
dominate disease presentation. Antidepressions are commonly prescribed for
depressive symptoms, but the evidence to support this practice is weak. The
atypical antipsychotics risperidone and olanzepine have significant efficacy for
the treatment of aggression and risperidone is also efficacious in the treatment
of psychosis, but both with substantially increased risk of stroke. There are no
newer studies of benzodiazepines in the treatment of anxiety and in old studies
the efficacy are doubtful.
PMID- 17032611
TI - [The future economic burden of dementia on health and social services].
AB - INTRODUCTION: Demographic changes in Denmark over the next 15 years will result
in an increased number of elderly people and of individuals with dementia. As a
result this will increase the demand for health care and social services. The aim
of this study was to shed light on the likely economic consequences of this
development. MATERIALS AND METHODS: A simple static, comparative model based on
Danish incidence and cost data for different age groups and different levels of
dementia severity was developed. The model projected the costs of the health and
social services for treatment and care of people with dementia up to the year
2020. RESULTS: The future demographic changes and an increasing number of people
with dementia will result in a 30% increase in health and social service costs
due to dementia. This increase will be lower if individuals with dementia have a
higher mortality rate than other individuals. If annual productivity gains of 1
3% can be achieved, the future cost (in real prices) could be reduced.
CONCLUSION: The Danish health and social services will in the future be faced
with increased costs for the treatment and care of people with dementia. This
could be achieved through productivity gains, an increased level of financing or
prioritisation of services that provide good value for money.
PMID- 17032612
TI - [Communications in health care-- with a focus on adult patients' and
children's/adolescents' perspectives of quality].
AB - In this article communications problems in health care are illuminated from the
perspectives of both adult patients and children. Factors that promote successful
communication are described and studies about the effect of communication courses
reviewed. Lack of information and responsiveness are among the problems most
often reported. The perspective of children and adolescents is a relatively
unexplored area. Studies investigating the effects of communication courses from
patients' perspectives are required.
PMID- 17032613
TI - [Sun and cancer].
PMID- 17032614
TI - Genotypic variation of N2-fixing common bean (Phaseolus vulgaris L.) in response
to iron deficiency.
AB - In calcareous soils, the yield of grain legumes is often limited by the lower
availability of iron (Fe), especially when they depend upon symbiosis with root
nodule bacteria for their N nutrition. In order to explore the variability of
responses of N(2)-fixing common bean to Fe deficiency the common bean white
seeded lines Striker and Coco blanc, and coloured-seeded lines SVM-29-21 and
ARA14 were inoculated with Rhizobium tropici (CIAT 899) and cultivated
hydroaeroponically with a N-free nutrient solution supplied or not with 45microM
Fe. Differences among lines were observed: Fe-deficiency-induced-chlorosis on
young leaves was earlier and more severe in some lines than others. Nodule
development and N(2)-fixing capacity was less affected in line ARA14 which
preferentially allocated Fe towards nodules. Results suggest that Fe use
efficiency for symbiotic nitrogen fixation (FeUE SNF) could be used to screen
tolerant bean lines to Fe deficiency in condition of symbiotic nitrogen fixation.
PMID- 17032615
TI - Reactive oxygen metabolism in mycorrhizal and non-mycorrhizal citrus (Poncirus
trifoliata) seedlings subjected to water stress.
AB - The effect of the arbuscular mycorrhizal (AM) fungus, Glomus versiforme, on
growth and reactive oxygen metabolism of trifoliate orange (Poncirus trifoliata)
seedlings was studied in potted plants under well-watered (WW) and water stressed
(WS) conditions. Water stress significantly decreased root colonization. Shoot
dry weight, plant height and stem diameter were higher in AM than in non-AM
seedlings regardless of the water status. Inoculation with G. versiforme
increased root dry weight and leaf number per plant of WW seedlings. There was
less malondialdehyde (MDA) concentration in leaves and roots of AM seedlings, as
well as lower hydrogen peroxide (H(2)O(2)) and superoxide anion radical (O(2)(-))
concentrations in AM roots under WW and WS conditions. AM inoculation did not
affect the H(2)O(2) and O(2)(-) concentrations of WW leaves. Whether WS or not,
AM symbiosis notably increased the guaiacol peroxidase (G-POD) activity of
leaves, glutathione reductase (GR) activity of leaves and ascorbate peroxidase
(APX) activity of roots. AM infection also markedly increased the APX activity of
WS leaves. Soluble proteins and glutathione (GSH) in leaves and roots and
ascorbate (ASC) in leaves were higher in WW AM than in WW non-AM seedlings. AM
infection also enhanced the ASC and GSH contents of leaves and roots in WS
seedlings. Cross-tolerance might occur in AM plants and be enhanced by AM
symbiosis. Our results suggest that the increased concentrations of antioxidant
enzymes and non-enzymatic antioxidants found in AM plants may serve to protect
the organism against oxidative damage, enhancing drought tolerance.
PMID- 17032616
TI - Salicylic acid accumulates in the roots and hypocotyl after inoculation of
cucumber leaves with Colletotrichum lagenarium.
AB - Increased amounts of salicylic acid (SA) were detected in the roots and hypocotyl
of cucumber plants (Cucumis sativus) using high-performance liquid chromatography
following inoculation of the leaves with the anthracnose pathogen, Colletotrichum
lagenarium. The concentrations of SA in the internodes immediately below the
infected leaves increased to more than 1microg/g fresh weight. In contrast, the
concentrations of SA in stems distant from, or above the infected leaves
increased to 100-300ng/g. An increase in SA levels was observed in the upper stem
2d after inoculation, followed by the hypocotyl with an increase detected 4d
after inoculation. An initial increase in the SA levels was detected in the stem,
followed by an increase in SA levels in the root from a basal level of
approximately 300ng/g to more than 1microg/g. The increased level of SA in the
lower leaves was less than 100ng/g. These results indicate that the levels of SA
in the hypocotyl and root increased significantly following inoculation of the
leaves with a microorganism capable of inducing SAR.
PMID- 17032617
TI - The reactive oxygen species are involved in resistance responses of wheat to the
Russian wheat aphid.
AB - The effect of Russian wheat aphid (RWA), Diuraphis noxia (Mordvilko), infestation
on the hydrogen peroxide (H(2)O(2)) content and NADPH oxidase (EC 1.6.3.1)
activity was studied in the resistant (cv. Tugela DN) and near-isogenic
susceptible (cv. Tugela) wheat (Triticum aestivum L.). The objective of this
study was to investigate the involvement of the reactive oxygen species (ROS)
during the resistance responses against the RWA. Infestation significantly
induced an early accumulation of the H(2)O(2) and increase of NADPH oxidase
activity to higher levels in the resistant than susceptible plants. Results of
inhibitory studies using diphenylene iodonium (DPI), a suicide inhibitor of NADPH
oxidase, strongly suggested a possible signalling role for H(2)O(2) during RWA
resistance response by activation of downstream defence enzymes [intercellular
peroxidase (EC 1.11.1.7) and beta-1,3-glucanase (EC 3.2.1.39)].
PMID- 17032618
TI - Thidiazuron influences the endogenous levels of cytokinins and IAA during the
flowering of isolated shoots of Dendrobium.
AB - This study reports the effects of thidiazuron (TDZ) on the endogenous levels of
indoleacetic acid (IAA), zeatin, zeatin riboside ([9R]Z), isopentenyladenine and
isopentenyladenosine ([9R]iP) as well as structural changes in the apical
meristem of Dendrobium Second Love shoots during flower induction and initial
development in vitro. The results revealed that the presence of 1.8microM TDZ had
a profound effect on the endogenous cytokinins (CKs) and IAA levels of the
explants, when compared to those grown on a TDZ-free medium. A significant
increase in CKs (especially [9R]iP and [9R]Z) and IAA in the first samples (taken
at day 5) grown on TDZ-enriched medium was associated with flower induction,
while a second increase in the level of these hormones after 25d of culture was
related to flower development. The histological changes detected in the shoot
apical meristem of explants grown in the presence of 1.8microM TDZ during 30d of
culture are also described. Based on these findings, it is suggested that both
auxin and CKs seem to be involved with the floral transition of Dendrobium Second
Love in vitro. However, a possible direct effect of TDZ on flower formation is
not discarded.
PMID- 17032619
TI - Transgenic Arabidopsis plants expressing the rice dehydroascorbate reductase gene
are resistant to salt stress.
AB - Vitamin C (l-ascorbate) is important for antioxidative and metabolic functions in
both plants and humans. Ascorbate itself is oxidized to dehydroascorbate during
the process of antioxidation, and dehydroascorbate reductase (DHAR, EC 1.8.5.1)
re-reduces the oxidized ascorbate. Therefore, this enzyme is assumed to be
critical for ascorbate recycling. Here we show that the expression of rice DHAR
in transgenic Arabidopsis thaliana enhanced resistance to salt stress. Salt
tolerance was remarkably improved despite slight increases in DHAR activity and
total ascorbate. This study provides direct evidence for the importance of DHAR
in salt tolerance.
PMID- 17032620
TI - Isolation of microprotoplasts from a partially synchronized suspension culture of
Citrus unshiu.
AB - The effect of hydroxyurea (HU) and amiprophos-methyl (APM) on the synchronization
of suspension cultures of Satsuma mandarin (Citrus unshiu) and micronucleation of
the suspension cells sequentially treated with both, HU and APM, were
investigated. When suspension cultures in early-log phase were treated with 4 or
10mM HU for 24h, the number of cells in the S-phase and the mitotic index (MI)
increased significantly. Exposure of the early-log phase suspension culture to
32microM APM led to a marked increase in the MI 12 and 24h after treatment, while
higher as well as lower concentrations (16, 24 and 48microM) had no effect.
Suspension cultures subjected to sequential treatment, e.g. pretreatment with
10mM HU for 24h followed by treatment with 32microM APM for 24h, also showed a
considerably increased MI. Furthermore, 61.5% of the protoplasts isolated from
the sequentially treated suspension cells were micronucleated, whereas only 3.6%
of the control protoplasts, isolated from untreated cells, showed
micronucleation. Ultra-centrifugation of the micronucleated protoplasts generated
microprotoplasts of different sizes, most of them below 5microM in diameter, with
1 or few chromosomes. The potential application of microprotoplasts in citrus
genetic improvement is discussed.
PMID- 17032621
TI - Changes in content and fatty acid profiles of total lipids of two halophytes:
Sesuvium portulacastrum and Mesembryanthemum crystallinum under cadmium stress.
AB - Changes in lipid content and fatty acid composition were determined in leaves of
two halophytes: Sesuvium portulacastrum and Mesembryanthemum crystallinum exposed
to cadmium (Cd). Experiments were carried out using young small-sized plants
grown hydroponically (S. portulacastrum) or aseptically germinated seeds (M.
crystallinum). Cd treatment was applied at different concentrations (0, 50, 100
and 200microM) for 30 days. At high cadmium doses (200microM), contents of total
lipids (TL) and lipid fractions including galactolipids (GL), phospholipids (PL)
and neutral lipids (NL) decreased more in M. crystallinum leaves than in S.
portulacastrum leaves. Moreover, there were no significant changes in the total
fatty acid composition of S. portulacastrum leaves during metal treatment. In
contrast, M. crystallinum leaves showed a decrease in the percentage of the tri
unsaturated fatty acid (C18:3), and a corresponding increase in the percentage of
di-unsaturated fatty acid (C18:2). These different responses suggested that S.
portulacastrum seems to be more feasible for phytoremediation.
PMID- 17032622
TI - Proteins induced by cadmium in soybean cells.
AB - The cadmium (Cd)-induced changes in protein pattern and identification of metal
stimulated polypeptides were analyzed in soybean cell suspension culture. The
cell cultures were treated with various concentrations of Cd(2+) (3-10microM) for
24, 48 and 72h. The synthesis of [(35)S]-labeled proteins and their accumulation
were analyzed by SDS-PAGE, whereas the identification of selected protein bands
was performed by mass spectrometry. It is shown that Cd induced the appearance of
the following proteins in soybean cells: superoxide dismutase, histone H2B,
chalcone synthase and glutathione transferase.
PMID- 17032623
TI - Research in shared decision making is growing deeper roots and more branches.
PMID- 17032625
TI - Comparison of composition and antifungal activity of Artemisia argyi Levl. et
Vant inflorescence essential oil extracted by hydrodistillation and supercritical
carbon dioxide.
AB - Essential oil of Artemisia argyi Levl. et Vant inflorescence was obtained by
supercritical CO(2) extraction and hydrodistillation. The oil was analyzed by gas
chromatography/mass spectrometry to characterize its components and was also
tested for antifungal activity. A total of 61 compounds were identified in the
hydrodistilled oil. The major components were 1,8-cineole (4.46%), borneol
(3.58%), terpinol (10.18%), spathulenol (10.03%), caryophyllene oxide (6.51%),
juniper camphor (8.74%), Camazulene (2.05%), and camphor (3.49%). By using
supercritical CO(2) at 50 degrees C and 10 MPa, the concentrations of previous
main components were lower than oil obtained by hydrodistillation, while
miscellaneous compounds were higher. The essential oil extracted by these two
methods exhibited antifungal activity against Botrytis cinerea and Alternaria
alternate, two common storage pathogens of fruits and vegetables. The inhibition
of B. cinerea and A. alternate were 93.3 and 84.7% for oil extracted by
hydrodistillation when exposed to a concentration of 1,000 mg L(-1), while values
of 70.8 and 60.5% were observed from oil extracted by supercritical CO(2).
PMID- 17032626
TI - Vascular endothelial growth factor and nitric oxide serum levels in arterial
hypertension.
AB - Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial
cells and an inducer of the angiogenic procedure. Endothelial nitric oxide (NO)
is a potent vasodilator. Because both are implicated in vascular function, it is
possible that they would be significantly affected in arterial hypertension. The
aim of the study was the investigation of the levels of the two substances in
blood serum and their potential relation in patients with untreated essential
arterial hypertension compared to healthy individuals. VEGF levels were found
129.1 +/- 135.9 pg/mL in a group of 28 untreated hypertensive patients vs. 209.0
+/- 133.3 pg/mL in a group of 28 healthy individuals (p = 0.008). Nitrites and
nitrates levels (as an indirect index of calculating NO levels) were also lower
in hypertensive patients than in healthy individuals (19.8 +/- 9.7 micromol/L vs.
29.6 +/- 15.9 micromol/L, p = 0.014). A positive correlation between NOx
(nitrites and nitrates levels) and VEGF was found in healthy individuals (r =
0.55, p = 0.003), but there was no correlation in hypertensive patients. The
significant decrease of serum VEGF and NO in arterial hypertension and the
existence of a correlation between the two substances in healthy subjects that
did not exist in the hypertensive patients are findings that need evaluation.
PMID- 17032627
TI - Marital decision-making and the timing of first birth in rural China before the
1990s.
AB - Using a sample of couples drawn from the three provinces of Guangdong, Shandong,
and Shaanxi, we investigated whether couples' increasing freedom to choose whom
to marry influenced the timing of first birth in rural China during the four
decades before the 1990s. The shortening of first-birth intervals in the period
is found to be associated with the shift from arranged to free-choice marriages.
The association is attributed largely to increased intimacy and coital frequency
after marriage together with postponement of age at first marriage.
PMID- 17032631
TI - Effect of gamma radiation on cytokine expression and cytokine-receptor mediated
STAT activation.
AB - PURPOSE: The expression of cytokine mRNA and their related transcription factors
was examined in order to assess the effects of gamma radiation on the immune
function of murine splenocytes. MATERIALS AND METHODS: Splenocytes were collected
from seven-week-old female Balb/c mice, and then irradiated at a dose of 5 Gy of
60Co gamma-ray at a dose rate of 1.394 Gy/min. Total RNA was extracted from both
irradiated and non-irradiated splenocytes at 1/2, 1, 3, 6, and 24 h and analysed
by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The mRNA
level of interferon (IFN)-gamma, which is a Th1-type (T helper cell type 1)
cytokine, was reduced after 3 h post-irradiation, whereas the interleukin (IL)-2
mRNA in the naive splenocytes had no significant changes within the 24 h after
irradiation. Moreover, IFN-gamma and IL-2 mRNA expression in concanavalin A (Con
A, 2.5 mug/ml) activated-splenocytes was significantly reduced by gamma
irradiation. On the other hand, the mRNA level of the Th2 type (T helper cell
type 2) cytokines, such as IL-4, IL-5 and IL-10, was increased both in naive and
activated splenocytes, and pro-inflammatory cytokines were also rapidly induced
in response to irradiation in naive splenocytes. Interestingly, gamma irradiation
had no effect on transforming growth factor (TGF)-beta mRNA expression. Moreover,
the mRNA levels of the leucine zipper trqnscription factor c-Maf and GATA binding
protein-3 (GATA-3), which regulate IL-4 and IL-5 transcription, were found to
have been up-regulated. However, the mRNA coding for interferon regulatory factor
(IRF)-1, which is involved in IFN-gamma production, was reduced 6 h post
irradiation. The level of signal transducers and activators of transcription
(Stat)-1 and Stat-4 phosphorylation, which are activated by IFN-gamma and IL-12,
respectively, was significantly reduced by gamma irradiation, but IL-4 receptor
mediated Stat-6 activation remained unchanged. CONCLUSIONS: These results suggest
that gamma irradiation may play a role in Th1 and Th2 cytokine expression, via
regulation of the level of cytokine-mediators through transcriptional modulation
and Stat signaling. These results are helpful to understand general profile of
cytokine expression in response to gamma irradiation.
PMID- 17032632
TI - Responding rapidly to FDA drug withdrawals: design and application of a new
approach for a consumer health website.
AB - BACKGROUND: Information about drug withdrawals may not reach patients in a timely
manner, and this could result in adverse events. Increasingly, the public turns
to consumer health websites for health information, but such sites may not update
their content for days or weeks following important events like Food and Drug
Administration (FDA) drug withdrawal actions. There is no recognized standard for
how quickly consumer health websites should respond to such events, and reports
addressing this issue are lacking. OBJECTIVE: The objective of this study was to
develop and implement an approach to enhance the efficiency with which a consumer
health website (NetWellness.org) responds to FDA drug withdrawal actions.
METHODS: Evaluation of the current approach used by NetWellness staff to update
content affected by FDA action revealed a slow process driven by the goal of
performing thorough and comprehensive review and editing. To achieve our desired
goal of accurately updating affected content within 24 hours of FDA action, we
developed a strategy that included rapid updating of affected Web pages with
warning boxes and hyperlinks to the information about the withdrawal. With the
next FDA withdrawal event, that of valdecoxib (Bextra) on April 7, 2005, we
applied this new approach, observed the time and resource requirements, and
monitored the rate at which consumers viewed the updated information to gauge its
potential impact. RESULTS: Application of the new approach allowed one person to
modify the affected Web pages in less than 1 hour and within 18 hours of the FDA
announcement. Using the old strategy, response to a similar event, the withdrawal
of rofecoxib (Vioxx) 6 months earlier, had taken over 3 weeks and the efforts of
several personnel. Updated valdecoxib content received 188 hits within the first
month and 4285 hits within 1 year. CONCLUSIONS: Rapid updating of a consumer
health website's content in response to an FDA drug withdrawal event was easily
accomplished by applying the approach described. This allowed consumers to view
accurate information regarding the withdrawn drug much sooner than would
otherwise have been the case. Given that consumers increasingly turn to websites
for their health information, adoption of a rapid response standard for important
health events like FDA drug withdrawals should be considered by the consumer
health informatics community.
PMID- 17032633
TI - Characterizing Internet searchers of smoking cessation information.
AB - BACKGROUND: The Internet is a viable channel to deliver evidence-based smoking
cessation treatment that has the potential to make a large population impact on
reducing smoking prevalence. There is high demand for smoking cessation
information and support on the Internet. Approximately 7% (10.2 million) of adult
American Internet users have searched for information on quitting smoking. Little
is known about these individuals, their smoking status, what type of cessation
services they are seeking on the Internet, or how frequently these searches for
cessation information are conducted. OBJECTIVE: The primary goal of this study
was to characterize individuals who search for smoking cessation information on
the Internet to determine appropriate triage and treatment strategies. The
secondary goal was to estimate the incidence of searches for cessation
information using publicly available search engine data. METHODS: We recruited
individuals who clicked on a link to a leading smoking cessation website
(QuitNet) from within the results of a search engine query. Individuals were
"intercepted" before seeing the QuitNet home page and were invited to participate
in the study. Those accepting the invitation were routed to an online survey
about demographics, smoking characteristics, preferences for specific cessation
services, and Internet search patterns. To determine the generalizability of our
sample, national datasets on search engine usage patterns, market share, and
keyword rankings were examined. These datasets were then used to estimate the
number of queries for smoking cessation information each year. RESULTS: During
the 10-day study period, 2265 individuals were recruited and 29% (N = 655)
responded. Of these, 59% were female and overall tended to be younger than the
previously characterized general Internet population. Most (76%) respondents were
current smokers; 17% had quit within the last 7 days, and 7% had quit more than 7
days ago. Slightly more than half of active smokers (53%) indicated that they
were planning to quit in the next 30 days. Smokers were more likely to seek
information on how to quit and on medications; former smokers were more
interested in how to cope with withdrawal. All participants rated withdrawal
information and individually tailored information as being more useful, while
displaying little interest in telephone counseling, expert support, or peer
support. Publicly available data from large search engines suggest that 4 million
Americans search for resources on smoking cessation each year. CONCLUSIONS: This
study adds to the limited data available on individuals who search for smoking
cessation information on the Internet, supports the prior estimates of the size
of the population, and indicates that these individuals are in appropriate stages
for both active cessation interventions and aggressive relapse prevention
efforts. Continued development and evaluation of online interventions is
warranted, and organizations seeking to promote cessation should carefully
evaluate the Internet as a possible modality for treatment and as a gateway to
other traditional programs.
PMID- 17032634
TI - Internet interventions or patient education web sites?
PMID- 17032636
TI - The law of attrition revisited.
PMID- 17032638
TI - Are physicians ready for patients with Internet-based health information?
AB - BACKGROUND: An increasing number of patients bring Internet-based health
information to medical consultations. However, little is known about how
physicians experience, manage, and view these patients. OBJECTIVE: This study
aimed to advance the understanding of the effects of incorporating Internet-based
health information into routine medical consultations from physicians'
perspectives, using a qualitative approach. METHODS: Six focus groups were
conducted with 48 family physicians practising in Toronto. The data were analyzed
using qualitative methods of content analysis and constant comparison, derived
from grounded theory approach. RESULTS: Three overarching themes were identified:
(1) perceived reactions of patients, (2) physician burden, and (3) physician
interpretation and contextualization of information. Physicians in our study
generally perceived Internet-based health information as problematic when
introduced by patients during medical consultations. They believed that Internet
information often generated patient misinformation, leading to confusion,
distress, or an inclination towards detrimental self-diagnosis and/or self
treatment. Physicians felt these influences added a new interpretive role to
their clinical responsibilities. Although most of the physicians felt obliged to
carry out this new responsibility, the additional role was often unwelcome.
Despite identifying various reactions of patients to Internet-based health
information, physicians in our study were unprepared to handle these patients.
CONCLUSION: Effective initiatives at the level of the health care system are
needed. The potential of Internet-based health information to lead to better
physician-patient communication and patient outcomes could be facilitated by
promoting physician acknowledgment of increasing use of the Internet among
patients and by developing patient management guidelines and incentives for
physicians.
PMID- 17032639
TI - Directions for the International Society for Research on Internet Interventions
(ISRII).
AB - In 2004, the International Society for Research on Internet Interventions (ISRII)
was formed to encourage eHealth researchers to collaborate in their efforts to
further the science behind developing, testing, and disseminating Web-based
treatment programs. The group held its second meeting (April 2006) to clarify the
Society's direction and identify key issues that need addressing in the field.
These issues are identified and examined in the current paper. Given the success
of using the Internet to treat a range of medical and mental health problems, and
the growing need for better dissemination of health care, Internet interventions
will almost certainly play a prominent role in global health. ISRII plans to
provide the necessary venue to ensure the science driving this field is strong,
enabling researchers to conduct the highest quality research and permitting
meaningful conclusions from completed studies.
PMID- 17032640
TI - Is e-health progressing faster than e-health researchers?
AB - Formal Internet interventions exist in a broad context of diverse online health
resources, which share elements in common like information, advice and peer
support. However, most online health resources are not created by healthcare
professionals. Internet interventions need to be designed to "compete" in that
wider context. The democratization of production and distribution is central to
the transformative effect of the Internet on society, yet potentially conflicts
with healthcare's need for an evidence base and safe practice. This is a core
challenge for healthcare on the Internet.
PMID- 17032641
TI - Global roles of Ste11p, cell type, and pheromone in the control of gene
expression during early sexual differentiation in fission yeast.
AB - Fission yeast cells belong to one of two specialized cell types, M or P. Specific
environmental conditions trigger sexual differentiation, which leads to an
internal program starting with pheromone signaling between M and P cells,
followed by mating, meiosis, and sporulation. The initial steps of this process
are controlled by Ste11p, a master transcriptional regulator that activates the
expression of cell type-specific genes (only expressed in either M or P cells) as
well as genes expressed in both M and P cells. Pheromone signaling is activated
by Ste11p-dependent transcription and, in turn, enhances some of this
transcription in a positive feedback. To obtain a genomewide view of Ste11p
target genes, their cell-type specificity, and their dependence on pheromone, we
used DNA microarrays along with different genetic and environmental manipulations
of fission yeast cells. We identified 78 Ste11p-dependent genes, 12 and 4 of
which are only expressed in M and P cells, respectively. These genes show
differing grades of pheromone dependencies for Ste11p-activated transcription,
ranging from complete independence to complete dependence on pheromone. We
systematically deleted all novel cell type-specific genes and characterized their
phenotype during sexual differentiation. A comparison with a similar data set
from the distantly related budding yeast reveals striking conservation in both
number and types of the proteins that define cell types. Given the divergent
mechanisms regulating cell type-specific gene expression, our results highlight
the plasticity of regulatory circuits, which evolve to allow adaptation to
changing environments and lifestyles.
PMID- 17032642
TI - Enhanced amyloidogenic metabolism of the amyloid beta-protein precursor in the
X11L-deficient mouse brain.
AB - X11L, a neuronal adaptor protein, associates with the cytoplasmic domain of APP
and suppresses APP cellular metabolism. APP is the precursor of Abeta, whose
metabolism is strongly implicated in Alzheimer disease pathogenesis. To examine
the roles of X11L function in APP metabolism, including the generation of Abeta
in the brain, we produced X11L-deficient mutant mice on the C57BL/6 background.
The mutant mice did not exhibit histopathological alterations or compensatory
changes in the expression of other X11 family proteins, X11 and X11L2. The
expression level and distribution of APP in the brain of mutant mice were also
identical to those in wild-type mice. However, in the hippocampus, where
substantial levels of X11L and APP are expressed, the mutant mice exhibited a
significant increase in the level of the C-terminal fragments of APP produced by
cleavage with beta-secretase but not alpha-secretase. The levels of Abeta were
increased in the hippocampus of aged mutant mice as compared with age-matched
controls. These observations clearly indicate that X11L suppresses the
amyloidogenic but not amyloidolytic processing of APP in regions of the brain
such as the hippocampus, which express significant levels of X11L.
PMID- 17032643
TI - Regulation of catalysis by the smallpox virus topoisomerase.
AB - The poxvirus type IB topoisomerases catalyze relaxation of supercoiled DNA by
cleaving and rejoining DNA strands via a pathway involving a covalent
phosphotyrosine intermediate. Recently we determined structures of the smallpox
virus topoisomerase bound to DNA in covalent and non-covalent DNA complexes using
x-ray crystallography. Here we analyzed the effects of twenty-two amino acid
substitutions on the topoisomerase activity in vitro in assays of DNA relaxation,
single cycle cleavage, and equilibrium cleavage-religation. Alanine substitutions
at 14 positions impaired topoisomerase function, marking a channel of
functionally important contacts along the protein-DNA interface. Unexpectedly,
alanine substitutions at two positions (D168A and E124A) accelerated the forward
rate of cleavage. These findings and further analysis indicate that Asp(168) is a
key regulator of the active site that maintains an optimal balance among the DNA
cleavage, religation, and product release steps. Finally, we report that high
level expression of the D168A topoisomerase in Escherichia coli, but not other
alanine-substituted enzymes, prevented cell growth. These findings help elucidate
the amino acid side chains involved in DNA binding and catalysis and provide
guidance for designing topoisomerase poisons for use as smallpox antivirals.
PMID- 17032644
TI - Biochemical and genetic analysis of methylenetetrahydrofolate reductase in
Leishmania metabolism and virulence.
AB - Methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) is the sole enzyme
responsible for generation of 5-methyltetrahydrofolate, which is required for
methionine synthesis and provision of methyl groups via S-adenosylmethionine.
Genome analysis showed that Leishmania species, unlike Trypanosoma brucei and
Trypanosoma cruzi, contain genes encoding MTHFR and two distinct methionine
synthases. Leishmania MTHFR differed from those in other eukaryotes by the
absence of a C-terminal regulatory domain. L. major MTHFR was expressed in yeast
and recombinant enzyme was produced in Escherichia coli. MTHFR was not inhibited
by S-adenosylmethionine and, uniquely among folate-metabolizing enzymes, showed
dual-cofactor specificity with NADH and NADPH under physiological conditions.
MTHFR null mutants (mthfr(-)) lacked 5-methyltetrahydrofolate, the most abundant
intracellular folate, and could not utilize exogenous homocysteine for growth.
Under conditions of methionine limitation mthfr(-) mutant cells grew poorly,
whereas their growth was normal in standard culture media. Neither in vitro MTHFR
activity nor the growth of mthfr(-) mutants or MTHFR overexpressors were
differentially affected by antifolates known to inhibit parasite growth via
targets beyond dihydrofolate reductase and pteridine reductase 1. In a mouse
model of infection mthfr(-) mutants showed good infectivity and virulence,
indicating that sufficient methionine is available within the parasitophorous
vacuole to meet the needs of the parasite.
PMID- 17032645
TI - Pre-steady state electrogenic events of Ca2+/H+ exchange and transport by the
Ca2+-ATPase.
AB - Native or recombinant SERCA (sarco(endo)plasmic reticulum Ca(2+) ATPase) was
adsorbed on a solid supported membrane and then activated with Ca(2+) and ATP
concentration jumps through rapid solution exchange. The resulting electrogenic
events were recorded as electrical currents flowing along the external circuit.
Current transients were observed following Ca(2+) jumps in the absence of ATP and
following ATP jumps in the presence of Ca(2+). The related charge movements are
attributed to Ca(2+) reaching its binding sites in the ground state of the enzyme
(E(1)) and to its vectorial release from the enzyme phosphorylated by ATP
(E(2)P). The Ca(2+) concentration and pH dependence as well as the time frames of
the observed current transients are consistent with equilibrium and pre-steady
state biochemical measurements of sequential steps within a single enzymatic
cycle. Numerical integration of the current transients recorded at various pH
values reveal partial charge compensation by H(+) in exchange for Ca(2+) at
acidic (but not at alkaline) pH. Most interestingly, charge movements induced by
Ca(2+) and ATP vary over different pH ranges, as the protonation probability of
residues involved in Ca(2+)/H(+) exchange is lower in the E(1) than in the E(2)P
state. Our single cycle measurements demonstrate that this difference contributes
directly to the reduction of Ca(2+) affinity produced by ATP utilization and
results in the countertransport of two Ca(2+) and two H(+) within each ATPase
cycle at pH 7.0. The effects of site-directed mutations indicate that Glu-771 and
Asp-800, within the Ca(2+) binding domain, are involved in the observed
Ca(2+)/H(+) exchange.
PMID- 17032646
TI - Identification and characterization of abeta1,3-glucosyltransferase that
synthesizes the Glc-beta1,3-Fuc disaccharide on thrombospondin type 1 repeats.
AB - Thrombospondin type 1 repeats (TSRs) are biologically important domains of
extracellular proteins. They are modified with a unique Glcbeta1,3Fucalpha1-O
linked disaccharide on either serine or threonine residues. Here we identify the
putative glycosyltransferase, B3GTL, as the beta1,3-glucosyltransferase involved
in the biosynthesis of this disaccharide. This enzyme is conserved from
Caenorhabditis elegans to man and shares 28% sequence identity with Fringe, the
beta1,3-N-acetylglucosaminyltransferase that modifies O-linked fucosyl residues
in proteins containing epidermal growth factor-like domains, such as Notch.
beta1,3-Glucosyltransferase glucosylates properly folded TSR-fucose but not
fucosylated epidermal growth factor-like domain or the non-fucosylated modules.
Specifically, the glucose is added in a beta1,3-linkage to the fucose in TSR. The
activity profiles of beta1,3-glucosyltransferase and protein O-fucosyltransferase
2, the enzyme that carries out the first step in TSR O-fucosylation, superimpose
in endoplasmic reticulum subfractions obtained by density gradient
centrifugation. Both enzymes are soluble proteins that efficiently modify
properly folded TSR modules. The identification of the beta1,3
glucosyltransferase gene allows us to manipulate the formation of the rare
Glcbeta1,3Fucalpha1 structure to investigate its biological function.
PMID- 17032647
TI - Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal
growth factor receptor-dependent ERK1/2 activation.
AB - Catecholamine-stimulated lipolysis is primarily a beta-adrenergic and cAMP
dependent event. In previous studies we established that the beta(3)-adrenergic
receptor (beta(3)AR) in adipocytes utilizes a unique mechanism to stimulate
extracellular signal-regulated kinases 1 and 2 (ERK) by direct recruitment and
activation of Src kinase. Therefore, we investigated the role of the ERK pathway
in adipocyte metabolism and found that the beta(3)AR agonist CL316,243 regulates
lipolysis through both cAMP-dependent protein kinase (PKA) and ERK. Inhibition of
PKA activity completely eliminated lipolysis at low (subnanomolar) CL316,243
concentrations and by 75-80% at higher nanomolar concentrations. The remaining 20
25% of PKA-independent lipolysis, as well as ERK activation, was abolished by
inhibiting the activity of either Src (PP2 or small interfering RNA), epidermal
growth factor receptor (EGFR with AG1478 or small interfering RNA), or mitogen
activated protein kinase kinase 1 or 2 (MKK1/2 with PD098059). PD098059 inhibited
lipolysis by 53% in mice as well. Finally, the effect of estradiol, a reported
acute activator of ERK and lipolysis, was also totally prevented by PP2, AG1478,
and PD098059. These results suggest that ERK activation by beta(3)AR depends upon
Src and epidermal growth factor receptor kinase activities and is responsible for
the PKA-independent portion of the lipolytic response. Together these results
illustrate the distinct and complementary roles for PKA and ERK in catecholamine
stimulated lipolysis.
PMID- 17032648
TI - Cathepsin D, a lysosomal protease, regulates ABCA1-mediated lipid efflux.
AB - To identify genes involved in the regulation of plasma high density lipoprotein
(HDL) cholesterol (HDL-C) levels, patients with low HDL-C and age- and sex
matched controls (normal HDL-C) were extensively characterized. Comparative
transcriptome analysis was carried out in cholesterol-loaded monocyte-derived
macrophages from low HDL subjects segregated into groups with or without
cholesterol efflux defects or ABCA1 mutations. Clusters of differentially
regulated genes were evident in the low HDL groups as compared with controls. Of
particular note, expression of cathepsin D (CTSD), a lysosomal proteinase, was
reduced by approximately 50% in monocyte-derived macrophages of low HDL-C
subjects, most significantly those with cholesterol efflux defects but without
mutations in ABCA1 (p < 0.01). These results were verified by reverse
transcription-PCR and replicated in a second cohort. We show here that blocking
the activity or expression of CTSD, by pepstatin or CTSD small interfering RNA,
respectively, reduced ABCA1 expression and protein abundance in both macrophages
and CHO cells and apolipoprotein A-I-mediated lipid efflux by more than 70%.
Conversely, expression of CTSD increased both ABCA1 mRNA expression and cellular
ABCA1 protein. Consistent with its role in the proteolytic processing of
prosaposin, inactivation of CTSD function resulted in the accumulation of
glycosphingo-lipid and free cholesterol in late endosomes/lysosomes, a phenotype
similar to NPC1 deficiency. Inhibition of CTSD also caused retention of ABCA1 in
lysosomal compartments, reducing its trafficking to the plasma membrane. These
studies demonstrate a novel and potentially important role for CTSD in
intracellular cholesterol trafficking and ABCA1-mediated efflux. Therefore,
decreased CTSD expression may contribute to low plasma HDL-C levels.
PMID- 17032649
TI - Rac1 GTPase regulates cell genomic stability and senescence.
AB - The Rho family small GTPase Rac1 has been shown to play multiple roles in cell
regulation, including actin cytoskeleton organization, transcriptional
activation, microtubule dynamics, and endocytosis. Here, we report a novel role
of Rac1 in regulating genomic stability and cell senescence. We observed in
primary mouse embryonic fibroblasts that deletion of rac1 by gene targeting, as
well as expression of the constitutively active Rac1 mutant L61Rac1, led to
decreased cell growth that was associated with altered cell cycle progression at
both G(1)/S and G(2)/M phases, increased apoptosis, and premature senescence. The
senescence induction by either loss or gain of Rac1 activity was due at least in
part to an increase in cellular reactive oxygen species (ROS). rac1 gene deletion
caused a compensatory up-regulation of a closely related family member, Rac3, in
mouse embryonic fibroblasts, the activity of which induced ROS production
independently of Rac1. Furthermore, the Rac1-regulated ROS production and
senescence correlated with the extent of DNA damage in the Rac1(-/-) and L61Rac1
cells. Treatment of these cells with a ROS inhibitor inhibited phospho-H2AX
positive nuclear focus formation. Finally, phospho-Ser(15) p53 was significantly
increased in L61Rac1 and Rac1(-/-) cells, and genetic deletion of p53 from these
cells readily reversed the senescence phenotype, indicating that Rac1 is
functionally dependent on p53 in regulating cell senescence. Taken together, our
results show that Rac1 activity serves as a regulator of cell senescence through
modulation of cellular ROS, genomic stability, and p53 activity.
PMID- 17032650
TI - Secretory granule biogenesis in sympathoadrenal cells: identification of a
granulogenic determinant in the secretory prohormone chromogranin A.
AB - Chromogranin A (CgA) may be critical for secretory granule biogenesis in
sympathoadrenal cells. We found that silencing the expression of CgA reduced the
number of secretory granules in normal sympathoadrenal cells (PC12), and we
therefore questioned whether a discrete domain of CgA might promote the formation
of a regulated secretory pathway in variant sympathoadrenal cells (A35C) devoid
of such a phenotype. The secretory granule-forming activity of a series of human
CgA domains labeled with a hemagglutinin epitope, green fluorescent protein, or
embryonic alkaline phosphatase was assessed in A35C cells by deconvolution and
electron microscopy and by secretagogue-stimulated release assays. Expression of
CgA in A35C cells induced the formation of vesicular organelles throughout the
cytoplasm, whereas two constitutive secretory pathway markers accumulated in the
Golgi complex. The lysosome-associated membrane protein LGP110 did not co
localize with CgA, consistent with non-lysosomal targeting of the granin in A35C
cells. Thus, CgA-expressing A35C cells showed electron-dense granules
approximately 180-220 nm in diameter, and secretagogue-stimulated exocytosis of
CgA from A35C cells suggested that expression of the granin may be sufficient to
restore a regulated secretory pathway and thereby rescue the sorting of other
secretory proteins. We show that the formation of vesicular structures destined
for regulated exocytosis may be mediated by a determinant located within the CgA
N-terminal region (CgA-(1-115), with a necessary contribution of CgA-(40-115)),
but not the C-terminal region (CgA-(233-439)) of the protein. We propose that CgA
promotes the biogenesis of secretory granules by a mechanism involving a
granulogenic determinant located within CgA-(40-115) of the mature protein.
PMID- 17032651
TI - Negative constraints underlie the ErbB specificity of epidermal growth factor
like ligands.
AB - Epidermal growth factor (EGF)-like growth factors bind their ErbB receptors in a
highly selective manner, but the molecular basis for this specificity is poorly
understood. We have previously shown that certain residues in human EGF (Ser(2)
Asp(3)) and TGFalpha (Glu(26)) are not essential for their binding to ErbB1 but
prevent binding to ErbB3 and ErbB4. In the present study, we have used a phage
display approach to affinity-optimize the C-terminal linear region of EGF-like
growth factors for binding to each ErbB receptor and thereby shown that Arg(45)
in EGF impairs binding to both ErbB3 and ErbB4. By omitting all these so-called
negative constraints from EGF, we designed a ligand designated panerbin that
binds ErbB1, ErbB3, and ErbB4 with similarly high affinity as their wild-type
ligands. Homology models, based on the known crystal structure of TGFalpha-bound
ErbB1, showed that panerbin is able to bind ErbB1, ErbB3, and ErbB4 in a highly
similar manner with respect to position and number of interaction sites. Upon in
silico introduction of the experimentally known negative constraints into
panerbin, we found that Arg(45) induced local charge repulsion and Glu(26)
induced steric hindrance in a receptor-specific manner, whereas Ser(2)-Asp(3)
impaired binding due to a disordered conformation. Furthermore, radiolabeled
panerbin was used to quantify the level of all three receptors on human breast
cancer cells in a single radioreceptor assay. It is concluded that the ErbB
specificity of EGF-like growth factors primarily results from the presence of a
limited number of residues that impair the unintended interaction with other ErbB
receptors.
PMID- 17032652
TI - Identification of a lipase-linked cell membrane receptor for pigment epithelium
derived factor.
AB - Pigment epithelium-derived factor (PEDF) is an extracellular multifunctional
protein belonging to the serpin superfamily with demonstrable neurotrophic,
gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. We
have previously provided biochemical evidence for high affinity PEDF-binding
sites and proteins in plasma membranes of retina, retinoblastoma, and CNS cells.
This study was designed to reveal a receptor involved in the biological
activities of PEDF. Using a yeast two-hybrid screening, we identified a novel
gene from pigment epithelium of the human retina that codes for a PEDF-binding
partner, which we term PEDF-R. The derived polypeptide has putative
transmembrane, intracellular and extracellular regions, and a phospholipase
domain. Recently, PEDF-R (TTS-2.2/independent phospholipase A(2) (PLA(2))zeta and
mouse desnutrin/ATGL) has been described in adipose cells as a member of the new
calcium-independent PLA(2)/nutrin/patatin-like phospholipase domain-containing 2
(PNPLA2) family that possesses triglyceride lipase and acylglycerol transacylase
activities. Here we describe the PEDF-R gene expression in the retina and its
heterologous expression by bacterial and eukaryotic systems, and we demonstrate
that its protein product has specific and high binding affinity for PEDF, has a
potent phospholipase A(2) activity that liberates fatty acids, and is associated
with eukaryotic cell membranes. Most importantly, PEDF binding stimulates the
enzymatic phospholipase A(2) activity of PEDF-R. In conclusion, we have
identified a novel PEDF-R gene in the retina for a phospholipase-linked membrane
protein with high affinity for PEDF, suggesting a molecular pathway by which
ligand/receptor interaction on the cell surface could generate a cellular signal.
PMID- 17032653
TI - Retinol dehydrogenase (RDH12) protects photoreceptors from light-induced
degeneration in mice.
AB - RDH12 has been suggested to be one of the retinol dehydrogenases (RDH) involved
in the vitamin A recycling system (visual cycle) in the eye. Loss of function
mutations in the RDH12 gene were recently reported to be associated with
autosomal recessive childhood-onset severe retinal dystrophy. Here we show that
RDH12 localizes to the photoreceptor inner segments and that deletion of this
gene in mice slows the kinetics of all-trans-retinal reduction, delaying dark
adaptation. However, accelerated 11-cis-retinal production and increased
susceptibility to light-induced photoreceptor apoptosis were also observed in
Rdh12(-/-) mice, suggesting that RDH12 plays a unique, nonredundant role in the
photoreceptor inner segments to regulate the flow of retinoids in the eye. Thus,
severe visual impairments of individuals with null mutations in RDH12 may likely
be caused by light damage(1).
PMID- 17032654
TI - Discovery of a new prokaryotic type I GTP cyclohydrolase family.
AB - GTP cyclohydrolase I (GCYH-I) is the first enzyme of the de novo tetrahydrofolate
biosynthetic pathway present in bacteria, fungi, and plants, and encoded in
Escherichia coli by the folE gene. It is also the first enzyme of the biopterin
(BH4) pathway in Homo sapiens, where it is encoded by a homologous folE gene. A
homology-based search of GCYH-I orthologs in all sequenced bacteria revealed a
group of microbes, including several clinically important pathogens, that encoded
all of the enzymes of the tetrahydrofolate biosynthesis pathway but GCYH-I,
suggesting that an alternate family was present in these organisms. A prediction
based on phylogenetic occurrence and physical clustering identified the COG1469
family as a potential candidate for this missing enzyme family. The GCYH-I
activity of COG1469 family proteins from a variety of sources (Thermotoga
maritima, Bacillus subtilis, Acinetobacter baylyi, and Neisseria gonorrhoeae) was
experimentally verified in vivo and/or in vitro. Although there is no detectable
sequence homology with the canonical GCYH-I, protein fold recognition based on
sequence profiles, secondary structure, and solvation potential information
suggests that, like GCYH-I proteins, COG1469 proteins are members of the tunnel
fold (T-fold) structural superfamily. This new GCYH-I family is found in
approximately 20% of sequenced bacteria and is prevalent in Archaea, but the
family is to this date absent in Eukarya.
PMID- 17032655
TI - Activation of platelet alphaIIbbeta3 by an exogenous peptide corresponding to the
transmembrane domain of alphaIIb.
AB - A transmembrane domain heterodimer, acting in concert with a membrane-proximal
cytoplasmic domain clasp, is thought to maintain integrins in a low affinity
state. To test whether helix-helix interactions between the alphaIIb and beta3
transmembrane domains regulate the activity of integrin alphaIIbbeta3, we
synthesized a soluble peptide corresponding to the alphaIIb transmembrane domain,
designated alphaIIb-TM, and we studied its ability to affect alphaIIbbeta3
activity in human platelets. alphaIIb-TM was alpha-helical in detergent micelles
and phospholipid vesicles, readily inserted into membrane bilayers, bound to
intact purified alphaIIbbeta3, and specifically associated with the transmembrane
domain of alphaIIb, rather than the transmembrane domains of beta3, alpha2, and
beta1, other integrin subunits present in platelets. When added to suspensions of
gel-filtered platelets, alphaIIb-TM rapidly induced platelet aggregation that was
not inhibited by preincubating platelets with the prostaglandin E(1) or the ADP
scavenger apyrase but was prevented by the divalent cation chelator EDTA.
Furthermore, alphaIIb-TM induced fibrinogen binding to platelets but not the
binding of osteopontin, a specific ligand for platelet alphavbeta3. The peptide
also induced fibrinogen binding to recombinant alphaIIbbeta3 expressed by Chinese
hamster ovary cells, confirming that its effect was independent of platelet
signal transduction. Finally, transmission electron microscopy of purified
alphaIIbbeta3 revealed that alphaIIb-TM shifted the integrin from a closed
configuration with its stalks touching to an open configuration with separated
stalks. These observations demonstrate that transmembrane domain interactions
regulate integrin function in situ and that it is possible to target intra
membranous protein-protein interactions in a way that can have functional
consequences.
PMID- 17032656
TI - Evidence for the formation of a heptameric ion channel complex by the hepatitis C
virus p7 protein in vitro.
AB - The p7 protein of hepatitis C virus functions as an ion channel both in vitro and
in cell-based assays and is inhibited by amantadine, long alkyl chain imino-sugar
derivatives, and amiloride compounds. Future drug design will be greatly aided by
information on the stoichiometry and high resolution structure of p7 ion channel
complexes. Here, we have refined a bacterial expression system for p7 based on a
glutathione S-transferase fusion methodology that circumvents the inherent
problems of hydrophobic protein purification and the limitations of chemical
synthesis. Rotational averaging and harmonic analysis of transmission electron
micrographs of glutathione S-transferase-FLAG-p7 fusion proteins in liposomes
revealed a heptameric stoichiometry. The oligomerization of p7 protein was then
confirmed by SDS-PAGE and mass spectrometry analysis of pure, concentrated FLAG
p7. The same protein was also confirmed to function as an ion channel in
suspended lipid bilayers and was inhibited by amantadine. These data validate
this system as a means of generating high resolution structural information on
the p7 ion channel complex.
PMID- 17032657
TI - Single strand annealing and ATP-independent strand exchange activities of yeast
and human DNA2: possible role in Okazaki fragment maturation.
AB - The Dna2 protein is a multifunctional enzyme with 5'-3' DNA helicase, DNA
dependent ATPase, 3' exo/endonuclease, and 5' exo/endonuclease. The enzyme is
highly specific for structures containing single-stranded flaps adjacent to
duplex regions. We report here two novel activities of both the yeast and human
Dna2 helicase/nuclease protein: single strand annealing and ATP-independent
strand exchange on short duplexes. These activities are independent of
ATPase/helicase and nuclease activities in that mutations eliminating either
nuclease or ATPase/helicase do not inhibit strand annealing or strand exchange.
ATP inhibits strand exchange. A model rationalizing the multiple catalytic
functions of Dna2 and leading to its coordination with other enzymes in
processing single-stranded flaps during DNA replication and repair is presented.
PMID- 17032658
TI - Conditional Akt activation promotes androgen-independent progression of prostate
cancer.
AB - Aggressive androgen-independent (also termed as hormone-refractory) prostate
cancer is a major clinical obstacle because there is no means to cure. Previous
studies have shown that Akt activation is associated with prostate cancer
progression from androgen-dependent to androgen-independent stage. However, its
causative role in this process has not been established. One of the major
limitations is the lack of a well-controlled inducible system to study Akt
involvement. Recently, we developed a novel inducible Akt (iAKT) system based on
a chemically induced dimerization (CID) approach. This system allows for
conditional activation of Akt in a physiological setting. Utilizing this iAKT
system, we found that Akt activation prevented cell death after serum withdrawal
and promoted cell proliferation in the absence of androgen in vitro in human
prostate cancer LNCaP cells, which should stop growing after androgen withdrawal
or even die after serum starvation. The iAKT-induced death protection and growth
promotion were further demonstrated in vivo using a transgenic mouse model that
expresses the iAKT system conditionally in the prostate epithelium. Most
importantly, in a mouse xenograft model derived from LNCaP cells, iAKT activation
promoted tumor growth in castrated animals by enhancing cell proliferation and
inhibiting apoptosis. Taken together, our data suggest that Akt activation is
playing a causative role in androgen-independent progression of prostate cancer.
This study provides a significant relevance of Akt-targeted therapy for hormone
refractory prostate cancers.
PMID- 17032659
TI - Soy isoflavonoid effects on endogenous estrogen metabolism in postmenopausal
female monkeys.
AB - Endogenous estrogens are important determinants of breast cancer risk in
postmenopausal women. In this study we evaluated the effects of dietary soy
isoflavonoids on endogenous estrogen metabolism in a postmenopausal primate
model. Ovariectomized female cynomolgus monkeys were randomized to receive one of
three diets for 36 months: (i) isoflavonoid-depleted soy protein isolate (SPI-)
(n = 29); (ii) soy protein isolate with 129 mg isoflavonoids/1800 kcal diet (8.6
mg isoflavonoids/kg body weight (BW), expressed in aglycone units) (SPI+) (n =
29) or (iii) isoflavonoid-depleted soy protein isolate with conjugated equine
estrogens (CEE) at a dose of 0.625 mg/1800 kcal diet (0.042 mg CEE/kg BW) (n =
30). Mean plasma isoflavonoid concentrations in the SPI+ group were 946.9 +/-
135.9 nmol/l, and equol was the primary circulating isoflavonoid (549.7 +/- 61.6
nmol/l). The SPI+ diet resulted in lower serum estrone (E(1)) after 29 (-26%, P =
0.03) and 34 months (-21%, P = 0.04) compared to the SPI- diet, while urinary 2
hydroxyestrone (P = 0.005) and the 2 to 16alpha-hydroxyestrone ratio (P < 0.0001)
were markedly higher in the SPI+ group compared to SPI-. Isoflavonoid treatment
did not significantly alter gene markers of estrogen metabolism or estrogen
receptor agonist activity in breast tissue. Within the SPI+ group, higher
concentrations of serum equol (but not daidzein or genistein) corresponded to
significantly lower serum E(1), mammary gland epithelial area and uterine weight
(P < 0.01 for all). These findings suggest that long-term exposure to soy
isoflavonoids, equol in particular, may facilitate endogenous estrogen clearance
and catabolism to more benign 2-hydroxylated metabolites.
PMID- 17032660
TI - Effects of chronic angiotensin II receptor antagonist and angiotensin-converting
enzyme inhibitor treatments on neurohormonal levels and haemodynamics during
cardiopulmonary bypass.
AB - BACKGROUND: Chronic treatment with renin-angiotensin system (RAS) antagonists
frequently causes deleterious hypotension during anaesthesia. We compared the
effects of angiotensin II receptor antagonists (ARA) and angiotensin-converting
enzyme inhibitors (ACEI) on neurohormonal levels and haemodynamics during
cardiopulmonary bypass (CPB). METHODS: Forty-four patients undergoing mitral
valvular surgery who were treated with either ARA (ARA group, n=14) or ACEI (ACEI
group, n=15) over 12 weeks or who were not treated with any RAS antagonist
(control group, n=15) were enrolled. The plasma levels of epinephrine,
norepinephrine, arginine vasopressin (AVP) and angiotensin II, and haemodynamic
variables were measured before (T1) and 15 min after (T2) the start of CPB,
before aortic unclamping (T3) and at skin closure (T4). Mean arterial pressure
(MAP) was maintained above 60 mm Hg with phenylephrine administration during CPB.
RESULTS: The plasma epinephrine, norepinephrine, AVP and angiotensin II levels
increased during CPB in all groups. Compared with the control group, the AVP
level was lower at T1 in the ARA group and at T2 in the ARA and ACEI groups. The
angiotensin II level was higher at T1, T2 and T3 in ARA group compared with ACEI
and control groups. There were no significant differences in the epinephrine and
norepinephrine levels among the three groups. The amount of administered
phenylephrine during CPB was greater and MAP was lower in the ARA group compared
with the ACEI and control groups. CONCLUSIONS: Chronic ARA treatment resulted in
more profound hypotension than ACEI treatment during CPB, and this may be
associated with the blockade of angiotensin II receptors by ARA.
PMID- 17032661
TI - The effects of propofol on neutrophil function, lipid peroxidation and
inflammatory response during elective coronary artery bypass grafting in patients
with impaired ventricular function.
AB - BACKGROUND: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass
elicits a potent reperfusion injury and inflammatory response, more intense in
patients with impaired myocardial function. Propofol has antioxidant properties
which may attenuate such a response. METHODS: In total, 27 patients with impaired
left ventricular function undergoing CABG were randomly allocated to receive
either target-controlled infusion propofol (P) or saline (S) immediately before
aortic cross-clamp release until 4 h after reperfusion. Troponin-I, Urinary 8-epi
PGF-2alpha isoprostane, coronary sinus and systemic malondialdehyde
concentrations, Interleukin-6 (IL-6), -8 and -10 concentrations and leucocytes
function studies (neutrophil respiratory burst, phagocytosis, CD-11b and CD-18
expression) were measured. RESULTS: Propofol decreased MDA coronary sinus
concentration at 1, 3 and 5 min after reperfusion (P<0.01); 60 min after
reperfusion a significant difference between the two groups in systemic MDA
concentrations was also seen. IL-6 concentration increases were significantly
greater in Group S than Group P, 4 h after reperfusion [1118 (1333) pg ml(-1) vs
228 (105) pg ml(-1), P<0.01]. Serum IL-8 concentrations did not increase
significantly in either group. Compared with baseline values IL-10 concentrations
decreased after reperfusion but the values were higher in the propofol group than
in the control group [22 (16) vs 11 (4) pg ml(-1), P<0.05]. No difference in
leucocyte function or urinary isoprostane concentrations was demonstrated.
CONCLUSION: Propofol attenuates free-radical-mediated lipid peroxidation and
systemic inflammation in patients with impaired myocardial function undergoing
CABG.
PMID- 17032662
TI - Continuous peripheral nerve block in combat casualties receiving low-molecular
weight heparin.
AB - BACKGROUND: Continuous peripheral nerve block (CPNB) is an important therapeutic
tool in the anaesthetic and analgesic management of combat casualties at Walter
Reed Army Medical Center (WRAMC). We describe our experience using CPNB
techniques in combat trauma patients treated with low-molecular weight heparin
(LMWH). Guidelines used at our institution for managing CPNB catheters in
patients being treated with LMWH are introduced. METHODS: From March 2003 to
April 2005, 187 combat casualties treated by the WRAMC regional anaesthesia/acute
pain section using CPNB were evaluated retrospectively by electronic chart
review. Patient characteristic data, CPNB type, duration of CPNB, indication for
LMWH [enoxaparin sodium injection (Lovenox-Sanofi Aventis, Bridgewater, NJ,
USA)], enoxaparin dose (mg) before and after catheter insertion and removal, time
from CPNB placement and removal to enoxaparin dose, and complications were
recorded. RESULTS: Median enoxaparin dose and time given before catheter
insertion were 30 mg and 21 h, respectively. Median enoxaparin dose was also 30
mg given a median of 12 h after peripheral nerve catheter placement. Catheters
remained in situ for a median of 8 days (range 1-33 days). Catheter specific
complications were infrequent and identified in 7 (3.7%) patients (two catheter
malfunction-kinking, catheter tip dislodgement in situ, two superficial catheter
site infections and two catheter dislocations). There were no catheter-related
bleeding complications evident in this study. CONCLUSIONS: Information regarding
the safety of CPNB in patients treated with LMWH for perioperative venous
thromboembolism prevention is scarce. Our initial experience with CPNB and
concurrent LMWH has not been complicated by catheter-related bleeding.
PMID- 17032663
TI - Modelling: a core technique in anaesthesia and critical care research.
PMID- 17032665
TI - Factors in epidural haematoma.
PMID- 17032664
TI - Propofol and memory.
PMID- 17032666
TI - Useful ectopics.
PMID- 17032667
TI - Facilitated insertion of a nasogastric tube in tracheal intubated patients using
the GlideScope.
PMID- 17032668
TI - Epidural anaesthesia for laparoscopic cholecystectomy in a patient with
scleroderma.
PMID- 17032669
TI - Strong magnesium solution.
PMID- 17032670
TI - Life-threatening spontaneous intracranial hypotension responding to epidural
blood patch.
PMID- 17032671
TI - Abdominal surgery, morbid obesity, age, dexamethasone, diabetes mellitus and
glucose metabolism.
PMID- 17032672
TI - Mutagenic activities and physicochemical properties of selected
nitrobenzanthrones.
AB - Mutagenic activity of nine nitro derivatives of benzanthrone, namely 1-nitro-, 2
nitro-, 3-nitro-, 9-nitro-, 11-nitro-, 1,9-dinitro-, 3,9-dinitro-, 3,11-dinitro-
and 3,9,11-trinitrobenzanthrone were tested with Salmonella strains TA98, TA100,
YG1021 and YG1024 in both the presence and absence of an S9 mix. Each compound
exhibited mutagenic activity with all the strains. Among these nine isomers, 3
nitrobenzantrone exhibited the most mutagenic activity with all the strains
without the S9 mix. The mutagenic activities of the dinitro and trinitro
derivatives of benzanthrone were lower than that of the 3-nitro derivative; this
is evident from the mutagenic activity of nitrated polyaromatic hydrocarbons
(PAH), which is generally enhanced with an increase in nitration. The
physicochemical properties of nitrated benzanthrone (reduction potential,
hydrophobicity and orientation of nitro groups to the aromatic ring) demonstrated
that mononitrated benzanthrone exhibits a lower reduction potential than
mononitroPAHs such as 1-nitropyrene and 3-nitrofluoranthene, but was almost
equivalent to that of dinitroPAH. Moreover, the mutagenic activity of
mononitrobenzanthrones clearly depend on the reduction potential of each
compound; however, this tendency was not observed in polynitrobenzanthrones,
probably because the reduction of the nitro groups to amino groups of
polynitrated benzanthrone might be predominant without a sufficient formation of
corresponding hydroxyamines. These results suggest that aromatic compounds that
contain keto groups, when nitrated, may act as potentially powerful direct-acting
mutagens.
PMID- 17032673
TI - Evaluating the performance of microarray segmentation algorithms.
AB - MOTIVATION: Although numerous algorithms have been developed for microarray
segmentation, extensive comparisons between the algorithms have acquired far less
attention. In this study, we evaluate the performance of nine microarray
segmentation algorithms. Using both simulated and real microarray experiments, we
overcome the challenges in performance evaluation, arising from the lack of
ground-truth information. The usage of simulated experiments allows us to analyze
the segmentation accuracy on a single pixel level as is commonly done in
traditional image processing studies. With real experiments, we indirectly
measure the segmentation performance, identify significant differences between
the algorithms, and study the characteristics of the resulting gene expression
data. RESULTS: Overall, our results show clear differences between the
algorithms. The results demonstrate how the segmentation performance depends on
the image quality, which algorithms operate on significantly different
performance levels, and how the selection of a segmentation algorithm affects the
identification of differentially expressed genes. AVAILABILITY: Supplementary
results and the microarray images used in this study are available at the
companion web site http://www.cs.tut.fi/sgn/csb/spotseg/
PMID- 17032674
TI - Large scale data mining approach for gene-specific standardization of microarray
gene expression data.
AB - MOTIVATION: The identification of the change of gene expression in multifactorial
diseases, such as breast cancer is a major goal of DNA microarray experiments.
Here we present a new data mining strategy to better analyze the marginal
difference in gene expression between microarray samples. The idea is based on
the notion that the consideration of gene's behavior in a wide variety of
experiments can improve the statistical reliability on identifying genes with
moderate changes between samples. RESULTS: The availability of a large collection
of array samples sharing the same platform in public databases, such as NCBI GEO,
enabled us to re-standardize the expression intensity of a gene using its mean
and variation in the wide variety of experimental conditions. This approach was
evaluated via the re-identification of breast cancer-specific gene expression. It
successfully prioritized several genes associated with breast tumor, for which
the expression difference between normal and breast cancer cells was marginal and
thus would have been difficult to recognize using conventional analysis methods.
Maximizing the utility of microarray data in the public database, it provides a
valuable tool particularly for the identification of previously unrecognized
disease-related genes. AVAILABILITY: A user friendly web-interface
(http://compbio.sookmyung.ac.kr/~lage/) was constructed to provide the present
large-scale approach for the analysis of GEO microarray data (GS-LAGE server).
PMID- 17032675
TI - KGraph: a system for visualizing and evaluating complex genetic associations.
AB - The KGraph is a data visualization system that has been developed to display the
complex relationships between the univariate and bivariate associations among an
outcome of interest, a set of covariates, and a set of genetic factors, such as
single nucleotide polymorphisms (SNPs). It allows for easy viewing and
interpretation of genetic associations, correlations among covariates and SNPs,
and information about the replication and cross-validation of the associations.
The KGraph allows the user to more easily investigate multicollinearity and
confounding through visualization of the multidimensional correlation structure
underlying genetic associations. It emphasizes gene-environment and gene-gene
interaction, both important components of any genetic system that are often
overlooked in association frameworks. AVAILABILITY:
http://www.epidkardia.sph.umich.edu/software/kgrapher
PMID- 17032676
TI - Robust method for detecting differential gene expression in twin studies.
AB - MOTIVATION: A steadily increasing number of experiments with microarrays
stimulate the further development of the statistical methods of the analysis of
gene expression data. One of the central problems in this area is detecting
differential gene expression under two or more conditions. Unfortunately, up to
now it has not been studied how the correlations between related individuals,
such as twins influence the estimates of differential gene expression. RESULTS:
In this paper, we discuss this problem and propose a new method that is robust
with respect to correlations of gene expression data for twins.
PMID- 17032677
TI - ChromoScan: a scan statistic application for identifying chromosomal regions in
genomic studies.
AB - ChromoScan is an implementation of a genome-based scan statistic that detects
genomic regions, which are statistically significant for targeted measurements,
such as genetic associations with disease, gene expression profiles, DNA copy
number variations, as well as other genome-based measurements. A Java graphic
user interface (GUI) is provided to allow users to select appropriate data
transformations and thresholds for defining the significant events. AVAILABILITY:
ChromoScan is freely available from
http://www.epidkardia.sph.umich.edu/software/chromoscan/
PMID- 17032678
TI - DASS: efficient discovery and p-value calculation of substructures in unordered
data.
AB - MOTIVATION: Pattern identification in biological sequence data is one of the main
objectives of bioinformatics research. However, few methods are available for
detecting patterns (substructures) in unordered datasets. Data mining algorithms
mainly developed outside the realm of bioinformatics have been adapted for that
purpose, but typically do not determine the statistical significance of the
identified patterns. Moreover, these algorithms do not exploit the often modular
structure of biological data. RESULTS: We present the algorithm DASS (Discovery
of All Significant Substructures) that first identifies all substructures in
unordered data (DASS(Sub)) in a manner that is especially efficient for modular
data. In addition, DASS calculates the statistical significance of the identified
substructures, for sets with at most one element of each type (DASS(P(set))), or
for sets with multiple occurrence of elements (DASS(P(mset))). The power and
versatility of DASS is demonstrated by four examples: combinations of protein
domains in multi-domain proteins, combinations of proteins in protein complexes
(protein subcomplexes), combinations of transcription factor target sites in
promoter regions and evolutionarily conserved protein interaction subnetworks.
AVAILABILITY: The program code and additional data are available at
http://www.fli-leibniz.de/tsb/DASS
PMID- 17032679
TI - Integration of gel-based proteome data with pProRep.
AB - pProRep is a web application integrating electrophoretic and mass spectral data
from proteome analyses into a relational database. The graphical web-interface
allows users to upload, analyse and share experimental proteome data. It offers
researchers the possibility to query all previously analysed datasets and can
visualize selected features, such as the presence of a certain set of ions in a
peptide mass spectrum, on the level of the two-dimensional gel. AVAILABILITY: The
pProRep package and instructions for its use can be downloaded from
http://www.ptools.ua.ac.be/pProRep. The application requires a web server that
runs PHP 5 (http://www.php.net) and MySQL. Some (non-essential) extensions need
additional freely available libraries: details are described in the installation
instructions.
PMID- 17032680
TI - Survival analysis of longitudinal microarrays.
AB - MOTIVATION: The development of methods for linking gene expressions to various
clinical and phenotypic characteristics is an active area of genomic research.
Scientists hope that such analysis may, for example, describe relationships
between gene function and clinical events such as death or recovery. Methods are
available for relating gene expression to measurements that are categorized or
continuous, but there is less work in relating expressions to an observed event
time such as time to death, response or relapse. When gene expressions are
measured over time, there are methods for differentiating temporal patterns.
However, methods have not yet been proposed for the survival analysis of
longitudinally collected microarrays. RESULTS: We describe an approach for the
survival analysis of longitudinal gene expression data. We construct a measure of
association between the time to an event and gene expressions collected over
time. Statistical significance is addressed using permutations and control of the
false discovery rate. Our proposed method is illustrated on a dataset from a
multi-center research study of inflammation and response to injury that aims to
uncover the biological reasons why patients can have dramatically different
outcomes after suffering a traumatic injury (www.gluegrant.org).
PMID- 17032681
TI - Meisetz and the birth of the KRAB motif.
AB - The largest family of transcription factors in mammals is of Cys(2)His(2) zinc
finger-proteins, each with an NH(2)-terminal KRAB motif. Extensive expansions of
this family have occurred in separate mammalian lineages, with approximately 400
such genes known in the human genome. Despite their widespread occurrence, the
evolutionary provenance of the KRAB motif is unclear since previously it has not
been found outside of the tetrapod vertebrates. Here, we show that homologues of
the histone methyltransferase Meisetz are present within the sea urchin
(Strongylocentrotus purpuratus) genome. Sea urchin and mammalian Meisetz
sequences each contain an N-terminal KRAB motif, which thereby establishes an
early origin of the KRAB motif prior to the divergence of echinoderm and chordate
lineages. Finally, we present evidence that KRAB motifs derive from a novel
family of KRI (KRAB Interior) motifs that were present in the last common
ancestor of animals, plants and fungi.
PMID- 17032682
TI - Identifying cis-regulatory modules by combining comparative and compositional
analysis of DNA.
AB - MOTIVATION: Predicting cis-regulatory modules (CRMs) in higher eukaryotes is a
challenging computational task. Commonly used methods to predict CRMs based on
the signal of transcription factor binding sites (TFBS) are limited by prior
information about transcription factor specificity. More general methods that
bypass the reliance on TFBS models are needed for comprehensive CRM prediction.
RESULTS: We have developed a method to predict CRMs called CisPlusFinder that
identifies high density regions of perfect local ungapped sequences (PLUSs) based
on multiple species conservation. By assuming that PLUSs contain core TFBS motifs
that are locally overrepresented, the method attempts to capture the expected
features of CRM structure and evolution. Applied to a benchmark dataset of CRMs
involved in early Drosophila development, CisPlusFinder predicts more annotated
CRMs than all other methods tested. Using the REDfly database, we find that some
'false positive' predictions in the benchmark dataset correspond to recently
annotated CRMs. Our work demonstrates that CRM prediction methods that combine
comparative genomic data with statistical properties of DNA may achieve
reasonable performance when applied genome-wide in the absence of an a priori set
of known TFBS motifs. AVAILABILITY: The program CisPlusFinder can be downloaded
at http://jakob.genetik.uni-koeln.de/bioinformatik/people/nora/nora.html. All
software is licensed under the Lesser GNU Public License (LGPL).
PMID- 17032683
TI - COPASI--a COmplex PAthway SImulator.
AB - MOTIVATION: Simulation and modeling is becoming a standard approach to understand
complex biochemical processes. Therefore, there is a big need for software tools
that allow access to diverse simulation and modeling methods as well as support
for the usage of these methods. RESULTS: Here, we present COPASI, a platform
independent and user-friendly biochemical simulator that offers several unique
features. We discuss numerical issues with these features; in particular, the
criteria to switch between stochastic and deterministic simulation methods,
hybrid deterministic-stochastic methods, and the importance of random number
generator numerical resolution in stochastic simulation. AVAILABILITY: The
complete software is available in binary (executable) for MS Windows, OS X, Linux
(Intel) and Sun Solaris (SPARC), as well as the full source code under an open
source license from http://www.copasi.org.
PMID- 17032684
TI - Structural genomics meets computational biology.
PMID- 17032685
TI - APDB: a web server to evaluate the accuracy of sequence alignments using
structural information.
AB - The APDB webserver uses structural information to evaluate the alignment of
sequences with known structures. It returns a score correlated to the overall
alignment accuracy as well as a local evaluation. Any sequence alignment can be
analyzed with APDB provided it includes at least two proteins with known
structures. Sequences without a known structure are simply ignored and do not
contribute to the scoring procedure. AVAILABILITY: APDB is part of the T-Coffee
suite of tools for alignment analysis, it is available on www.tcoffee.org. A
stand-alone version of the package is also available as a freeware open source
from the same address.
PMID- 17032688
TI - Improvement of left ventricular diastolic function after alcohol septal ablation
for obstructive hypertrophic cardiomyopathy? Yes, of course, but...
PMID- 17032686
TI - Administration of efavirenz (600 mg/day) with rifampicin results in highly
variable levels but excellent clinical outcomes in patients treated for
tuberculosis and HIV.
AB - OBJECTIVES: Pharmacokinetic interactions between rifampicin and antiretroviral
therapy (ART), including efavirenz, are problematic and need to be better defined
to determine proper dose and to be correlated with short-term and long-term
clinical outcomes. PATIENTS AND METHODS: Consenting patients with smear-positive
pulmonary TB and HIV received once daily didanosine + lamivudine + efavirenz (600
mg), with rifampicin-containing TB regimen by directly observed therapy and self
administration at TB therapy completion. Trough efavirenz levels were measured by
HPLC at 1, 2, 4 and 6 months while on rifampicin and after discontinuation. HIV
and TB outcomes were monitored. RESULTS: Twenty African patients were enrolled
[15 female, mean age 31 years, baseline weight 59.4 kg (range 45-97), viral load
5.75 log10 copies/mL and CD4 230 cells/mm3]. Seventy-two efavirenz concentrations
were available from 19 patients (58 on, 14 after rifampicin). The geometric mean
efavirenz concentration was 1730 ng/mL (range 354-27,179) on and 1377 ng/mL
(range 572-3975) off rifampicin (P = 0.55). Inter-subject variability in
efavirenz concentrations was greater on rifampicin (CV 157% versus 58% off) with
relatively consistent intra-subject variation over time (median CV 24%). Over
half of patients had efavirenz concentrations above or below the expected
therapeutic range (1000-4000 ng/mL). Efavirenz levels were not predicted by
weight or gender and were not associated with HIV clinical outcomes. Overall 80%
of patients had non-detectable viral loads at 6 months and 65% at 21 months with
a cumulative CD4 cell increase of 196 cells/mm3. CONCLUSIONS: In this
longitudinal study, despite wide variability in plasma efavirenz concentrations
during rifampicin administration, excellent clinical outcomes were obtained. In
African patients treated for HIV and TB, our data support the routine use of
efavirenz at 600 mg/day when receiving rifampicin.
PMID- 17032687
TI - Evaluation of a regional disease management programme for patients with asthma or
chronic obstructive pulmonary disease.
AB - OBJECTIVE: To assess the impact of a population-based disease management
programme for adult patients with asthma or chronic obstructive pulmonary disease
(COPD) on process measures, intermediate outcomes, and endpoints of care. DESIGN:
Quasi-experimental design with 12-month follow-up. SETTING: Region of Maastricht
(the Netherlands) including university hospital and 16 general practices.
PARTICIPANTS: Nine hundred and seventy-five patients of whom 658 have asthma and
317 COPD. INTERVENTION: Disease management programme. MAIN OUTCOME MEASURE(S):
Endpoints of care are respiratory health, health utility, patient satisfaction,
and total health care costs related to asthma or COPD. RESULTS: Quality aspects
of care, disease control, self-care behaviour, smoking status, disease-specific
knowledge, and patients' satisfaction improved after implementation of the
programme. Lung function was not affected by implementation of the programme. For
COPD patients, a significant improvement in health utility was found. For
patients with asthma, significant cost savings were measured. CONCLUSIONS:
Organizing health care according to principles of disease management for adults
with asthma or COPD is associated with significant improvements in several
processes and outcomes of care, while costs of care do not exceed the existing
budget.
PMID- 17032689
TI - The high cost of implantable defibrillators.
AB - Increased use of ICDs in patients with cardiac disease has the potential to
strain national health care budgets because of the large numbers of eligible
patients and the high cost of the ICDs. Randomized trials show ICDs increase life
expectancy in some groups of patients and also increase total medical costs
significantly. ICDs exemplify the role of new technology as the main force behind
rising health care costs. ICDs have not been used in all eligible patients, in
part because of cost, but also because of patient resistance and a shortage of
specialists able to implant and manage complex ICDs. The cost-effectiveness of
ICDs would be improved by development of simpler and cheaper devices, and by
better tools to identify patients who benefit from an ICD.
PMID- 17032690
TI - Clinical and prognostic profile of patients with infective endocarditis who need
urgent surgery.
AB - AIMS: Surgery in patients with infective endocarditis (IE) can be elective (upon
completion of antibiotic treatment) or urgent (before antibiotic treatment has
ended) when the clinical course is unfavourable. However, urgent surgery for left
sided endocarditis is associated with high mortality. The aims of this study were
to describe the profile of patients with left-sided endocarditis who underwent
urgent surgery and to analyse the factors that predicted mortality. METHODS AND
RESULTS: Among 508 consecutive episodes of IE, 391 were left-sided and 89
required urgent surgery. The main reasons for urgent surgery were heart failure
that did not respond to medication (72%) and persistent infection despite
appropriate antibiotic treatment (31%). Thirty-two patients (36%) died during
their hospital stay. Univariate analysis identified renal failure, septic shock,
Gram-negative bacteria, persistent infection, and surgery for persistent
infection as factors associated with mortality. Multivariate analysis confirmed
only persistent infection and renal insufficiency as factors independently
associated with a poor prognosis. CONCLUSION: Patients with IE who need urgent
surgery have a poor clinical course. Heart failure, the main cause of urgent
surgery, was not associated with higher mortality. However, persistent infection
and renal failure were factors associated with higher post-surgical mortality.
PMID- 17032691
TI - Prediction of risk of death and myocardial infarction in the six months after
presentation with acute coronary syndrome: prospective multinational
observational study (GRACE).
AB - OBJECTIVE: To develop a clinical risk prediction tool for estimating the
cumulative six month risk of death and death or myocardial infarction to
facilitate triage and management of patients with acute coronary syndrome.
DESIGN: Prospective multinational observational study in which we used
multivariable regression to develop a final predictive model, with prospective
and external validation. SETTING: Ninety four hospitals in 14 countries in
Europe, North and South America, Australia, and New Zealand. POPULATION: 43,810
patients (21,688 in derivation set; 22,122 in validation set) presenting with
acute coronary syndrome with or without ST segment elevation enrolled in the
global registry of acute coronary events (GRACE) study between April 1999 and
September 2005. MAIN OUTCOME MEASURES: Death and myocardial infarction. RESULTS:
1989 patients died in hospital, 1466 died between discharge and six month follow
up, and 2793 sustained a new non-fatal myocardial infarction. Nine factors
independently predicted death and the combined end point of death or myocardial
infarction in the period from admission to six months after discharge: age,
development (or history) of heart failure, peripheral vascular disease, systolic
blood pressure, Killip class, initial serum creatinine concentration, elevated
initial cardiac markers, cardiac arrest on admission, and ST segment deviation.
The simplified model was robust, with prospectively validated C-statistics of
0.81 for predicting death and 0.73 for death or myocardial infarction from
admission to six months after discharge. The external applicability of the model
was validated in the dataset from GUSTO IIb (global use of strategies to open
occluded coronary arteries). CONCLUSIONS: This risk prediction tool uses readily
identifiable variables to provide robust prediction of the cumulative six month
risk of death or myocardial infarction. It is a rapid and widely applicable
method for assessing cardiovascular risk to complement clinical assessment and
can guide patient triage and management across the spectrum of patients with
acute coronary syndrome.
PMID- 17032692
TI - Classification of G-protein coupled receptors at four levels.
AB - G-protein coupled receptors (GPCRs) are transmembrane proteins which via G
proteins initiate some of the important signaling pathways in a cell and are
involved in various physiological processes. Thus, computational prediction and
classification of GPCRs can supply significant information for the development of
novel drugs in pharmaceutical industry. In this paper, a nearest neighbor method
has been introduced to discriminate GPCRs from non-GPCRs and subsequently
classify GPCRs at four levels on the basis of amino acid composition and
dipeptide composition of proteins. Its performance is evaluated on a non
redundant dataset consisted of 1406 GPCRs for six families and 1406 globular
proteins using the jackknife test. The present method based on amino acid
composition achieved an overall accuracy of 96.4% and Matthew's correlation
coefficient (MCC) of 0.930 for correctly picking out the GPCRs from globular
proteins. The overall accuracy and MCC were further enhanced to 99.8% and 0.996
by dipeptide composition-based method. On the other hand, the present method has
successfully classified 1406 GPCRs into six families with an overall accuracy of
89.6 and 98.8% using amino acid composition and dipeptide composition,
respectively. For the subfamily prediction of 1181 GPCRs of rhodopsin-like
family, the present method achieved an overall accuracy of 76.7 and 94.5% based
on the amino acid composition and dipeptide composition, respectively. Finally,
GPCRs belonging to the amine subfamily and olfactory subfamily of rhodopsin-like
family were further analyzed at the type level. The overall accuracy of dipeptide
composition-based method for the classification of amine type and olfactory type
of GPCRs reached 94.5 and 86.9%, respectively, while the overall accuracy of
amino acid composition-based method was very low for both subfamilies. In
comparison with existing methods in the literature, the present method also
displayed great competitiveness. These results demonstrate the effectiveness of
our method on identifying and classifying GPCRs correctly. GPCRsIdentifier, a
corresponding stand-alone executable program for GPCR identification and
classification was also developed, which can be acquired freely on request from
the authors for academic purposes.
PMID- 17032693
TI - Size-resolved sulfuric acid mist concentrations at phosphate fertilizer
manufacturing facilities in Florida.
AB - Strong inorganic acid mists containing sulfuric acid were identified as a 'known
human carcinogen' in a National Toxicology Program (NTP) report where phosphate
fertilizer manufacture was listed as one of many occupational exposures to strong
acids. To properly assess the occupational exposure to sulfuric acid mists in
modern facilities, approved National Institute for Occupational Safety and Health
(NIOSH) Method 7903 and a cascade impactor were used for measuring the total
sulfuric acid mist concentration and size-resolved sulfuric acid mist
concentration, respectively. Sampling was conducted at eight phosphate fertilizer
plants and two background sites in Florida and there were 24 sampling sites in
these plants. Samples were analyzed by ion chromatography (IC) to quantify the
water-soluble ion species. The highest sulfuric acid concentrations by the
cascade impactor were obtained at the sulfuric acid pump tank area. When high
aerosol mass concentrations (100 micro g m(-3)) were observed at this area, the
sulfuric acid mists were in the coarse mode. The geometric mean sulfuric acid
concentrations (+/-geometric standard deviation) of PM(23) (aerodynamic cut size
smaller than 23 micro m), PM(10) and PM(2.5) from the cascade impactor were 41.7
(+/-5.5), 37.9 (+/-5.8) and 22.1 (+/-4.5) micro g m(-3), respectively. The
geometric mean (+/-geometric standard deviation) for total sulfuric acid
concentration from the NIOSH method samples was 143 (+/-5.08) micro g m(-3).
Sulfuric acid mist concentrations varied significantly among the plants and even
at the same location. The measurements by the NIOSH method were 1.5-229 times
higher than those by the cascade impactor. Moreover, using the NIOSH method, the
sulfuric acid concentrations measured at the lower flow rate (0.30 Lpm) were
higher than those at the higher flow rate (0.45 Lpm). One possible reason for the
significant differences between the results from the cascade impactor and the
NIOSH method is the potential artifact resulting from the interaction of SO(2)
with silica gel and glass fiber used in the NIOSH method.
PMID- 17032694
TI - Living near main streets and respiratory symptoms in adults: the Swiss Cohort
Study on Air Pollution and Lung Diseases in Adults.
AB - The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA),
conducted in 1991 (SAPALDIA 1) in eight areas among 9,651 randomly selected
adults aged 18-60 years, reported associations among the prevalence of
respiratory symptoms, nitrogen dioxide, and particles with an aerodynamic
diameter of less than 10 microg/m3. Later, 8,047 subjects reenrolled in 2002
(SAPALDIA 2). The effects of individually assigned traffic exposures on reported
respiratory symptoms were estimated, while controlling for socioeconomic and
exposure- and health-related factors. The risk of attacks of breathlessness
increased for all subjects by 13% (95% confidence interval: 3, 24) per 500-m
increment in the length of main street segments within 200 m of the home and
decreased in never smokers by 12% (95% confidence interval: 0, 22) per 100-m
increment in distance from home to a main street. Living within 20 m of a main
street increased the risks of regular phlegm by 15% (95% confidence interval: 0,
31) and wheezing with breathing problems by 34% (95% confidence interval: 0, 79)
in never smokers. In 2002, the effects related to road distance were different
from those in 1991, which could be due to changes in the traffic pollution
mixture. These findings among a general population provide strong confirmation
that living near busy streets leads to adverse respiratory health effects.
PMID- 17032695
TI - Violence and psychiatric morbidity in a national household population--a report
from the British Household Survey.
AB - This study measured the prevalence of self-reported violence and associations
with psychiatric morbidity in a national household population, based on a cross
sectional survey in 2000 of 8,397 respondents in Great Britain. Diagnoses were
derived from computer-assisted interviews, with self-reported violent behavior
over the previous 5 years. The 5-year prevalence of nonlethal violence in Britain
was 12% (95% confidence interval: 11, 13). The risk of violence was substantially
increased by alcohol dependence (odds ratio=2.72, 95% confidence interval: 1.85,
3.98), drug dependence (odds ratio=2.63, 95% confidence interval: 1.45, 4.74),
and antisocial personality disorder (odds ratio=6.12, 95% confidence interval:
3.87, 9.66). Low prevalences of these conditions (7%, 4%, and 4%, respectively)
contrasted with their relatively high proportions of attributed risk of violence
(23%, 15%, and 15%). Hazardous drinking was associated with 56% of all reported
violent incidents. Screening positive for psychosis did not independently
increase risk (odds ratio=3.20, 95% confidence interval: 0.35, 29.6). The study
concluded that psychiatric morbidity makes a significant public health impact on
violence exerted primarily by persons with any personality disorder, substance
dependence, and hazardous drinking. Population interventions for violent behavior
are appropriate for hazardous drinking as are targeted interventions for
substance dependence and antisocial personality disorder. Despite public concern,
the risks of violence from persons with severe mental illness were very low.
PMID- 17032696
TI - High cumulative risk of lung cancer death among smokers and nonsmokers in Central
and Eastern Europe.
AB - The authors have calculated cumulative risks of lung cancer from a case-control
study conducted between 1998 and 2002 involving 2,633 lung cancer cases and 2,884
controls in Hungary, Poland, the Czech Republic, Slovakia, Romania, and Russia.
The odds ratios for smoking history were combined with national lung cancer
mortality rates to obtain the cumulative risk of lung cancer. The cumulative risk
of death from lung cancer by the age of 75 years among current male smokers was
14.6% in Romania and Russia and 15.8% in Poland, similar to levels reported in
Western Europe, although higher risks were found in the Czech Republic (19.8%),
Hungary (21.9%), and Slovakia (28.2%). Cumulative risks of lung cancer death
among never smokers of over 1% were observed in Hungary among both men and women
and among men in Poland. The effect of quitting smoking on the lifetime
cumulative risk was substantial, with between 67% and 83% of lung cancer risk
among men being avoided by quitting before the age of 50 years. This substantial
reduction in risk among former smokers confirms that lung cancer mortality in
Central Europe over the next three decades will be determined by the extent to
which current smokers can successfully quit smoking.
PMID- 17032697
TI - DAMPs, PAMPs and alarmins: all we need to know about danger.
AB - Multicellular animals detect pathogens via a set of receptors that recognize
pathogen-associated molecular patterns (PAMPs). However, pathogens are not the
only causative agents of tissue and cell damage: trauma is another one. Evidence
is accumulating that trauma and its associated tissue damage are recognized at
the cell level via receptor-mediated detection of intracellular proteins released
by the dead cells. The term "alarmin" is proposed to categorize such endogenous
molecules that signal tissue and cell damage. Intriguingly, effector cells of
innate and adaptive immunity can secrete alarmins via nonclassical pathways and
often do so when they are activated by PAMPs or other alarmins. Endogenous
alarmins and exogenous PAMPs therefore convey a similar message and elicit
similar responses; they can be considered subgroups of a larger set, the damage
associated molecular patterns (DAMPs).
PMID- 17032698
TI - Mining literature for systems biology.
AB - Currently, literature is integrated in systems biology studies in three ways.
Hand-curated pathways have been sufficient for assembling models in numerous
studies. Second, literature is frequently accessed in a derived form, such as the
concepts represented by the Medical Subject Headings (MeSH) and Gene Ontologies
(GO), or functional relationships captured in protein-protein interaction (PPI)
databases; both of these are convenient, consistent reductions of more complex
concepts expressed as free text in the literature. Moreover, their contents are
easily integrated into computational processes required for dealing with large
data sets. Last, mining text directly for specific types of information is on the
rise as text analytics methods become more accurate and accessible. These uses of
literature, specifically manual curation, derived concepts captured in ontologies
and databases, and indirect and direct application of text mining, will be
discussed as they pertain to systems biology.
PMID- 17032699
TI - An informative Bayesian structural equation model to assess source-specific
health effects of air pollution.
AB - A primary objective of current air pollution research is the assessment of health
effects related to specific sources of air particles or particulate matter (PM).
Quantifying source-specific risk is a challenge because most PM health studies do
not directly observe the contributions of the pollution sources themselves.
Instead, given knowledge of the chemical characteristics of known sources,
investigators infer pollution source contributions via a source apportionment or
multivariate receptor analysis applied to a large number of observed elemental
concentrations. Although source apportionment methods are well established for
exposure assessment, little work has been done to evaluate the appropriateness of
characterizing unobservable sources thus in health effects analyses. In this
article, we propose a structural equation framework to assess source-specific
health effects using speciated elemental data. This approach corresponds to
fitting a receptor model and the health outcome model jointly, such that
inferences on the health effects account for the fact that uncertainty is
associated with the source contributions. Since the structural equation model
(SEM) typically involves a large number of parameters, for small-sample settings,
we propose a fully Bayesian estimation approach that leverages historical
exposure data from previous related exposure studies. We compare via simulation
the performance of our approach in estimating source-specific health effects to
that of 2 existing approaches, a tracer approach and a 2-stage approach.
Simulation results suggest that the proposed informative Bayesian SEM is
effective in eliminating the bias incurred by the 2 existing approaches, even
when the number of exposures is limited. We employ the proposed methods in the
analysis of a concentrator study investigating the association between ST
segment, a cardiovascular outcome, and major sources of Boston PM and discuss the
implications of our findings with respect to the design of future PM concentrator
studies.
PMID- 17032700
TI - Association of CXCR4 and CCR7 chemokine receptor expression and lymph node
metastasis in human cervical cancer.
AB - BACKGROUND: The chemokine receptors CXCR4 and CCR7 have been suggested to play an
important role in cancer invasion and metastasis. The expression of these
receptors in human cervical cancer, however, has seldom been characterized.
PATIENTS AND METHODS: We investigated the expression of CXCR4 and CCR7 in
cervical cancer specimens and determined the association between their expression
and the clinicopathological features observed, including patient outcome.
RESULTS: CXCR4 expression was significantly higher in elderly patients (P=0.025);
it was also significantly increased in patients with cancers displaying large
tumor size (P=0.010), deep stromal invasion (P=0.0004), lymph-vascular space
involvement (P=0.0002), or lymph node metastasis (P<0.0001). CCR7 expression was
significantly higher in cases of squamous cell carcinomas (P=0.010) and in
patients with cancers showing large tumor size (P<0.0001), deep stromal invasion
(P<0.0001), vaginal invasion (P=0.047), lymph-vascular space involvement
(P=0.012), or lymph node metastasis (P<0.0001). Logistic regression analysis
revealed that deep stromal invasion (P=0.017) and CXCR4 (P=0.016) and CCR7
(P=0.022) expression were independent factors that influenced pelvic lymph node
metastasis. The disease-free survival and overall survival (OS) rates of patients
exhibiting both CXCR4 and CCR7 expression were significantly reduced (P<0.0001).
In addition, the expression of both CXCR4 and CCR7 was an independent prognostic
factor for OS (95% confidence interval=1.03-17.86; P=0.046). CONCLUSIONS: CXCR4
and CCR7 expression may be associated with lymph node metastasis; moreover, the
expression of these receptors can serve as an indicator of poor prognosis in
patients with cervical cancer.
PMID- 17032701
TI - Toxicokinetics of inhaled trichloroethylene and tetrachloroethylene in humans at
1 ppm: empirical results and comparisons with previous studies.
AB - Trichloroethylene (TRI) and tetrachloroethylene (TETRA) are solvents that have
been widely used in a variety of industries, and both are widespread
environmental contaminants. In order to provide a better basis for understanding
their toxicokinetics at environmental exposures, seven human volunteers were
exposed by inhalation to 1 ppm of TRI or TETRA for 6 h, with biological samples
collected for analysis during exposure and up to 6-days postexposure.
Concentrations of TRI, TETRA, free trichloroethanol (TCOH), total TCOH (free TCOH
plus glucuronidated TCOH), and trichloroacetic acid (TCA) were determined in
blood and urine; TRI and TETRA concentrations were measured in alveolar breath.
Toxicokinetic time courses and empirical analyses of classical toxicokinetic
parameters were compared with those reported in previous human volunteer studies,
most of which involved exposures that were at least 10-fold higher.
Qualitatively, TRI and TETRA toxicokinetics were consistent with previous human
studies. Quantitatively, alveolar retention and clearance by exhalation were
similar to those found previously but blood and urine data suggest a number of
possible toxicokinetic differences. For TRI, data from the current study support
lower apparent blood-air partition coefficients, greater apparent metabolic
clearance, less TCA production, and greater glucuronidation of TCOH as compared
to previous studies. For TETRA, the current data suggest TCA formation that is
similar or slightly lower than that of previous studies. Variability and
uncertainty in empirical estimates of total TETRA metabolism are substantial,
with confidence intervals among different studies substantially overlapping.
Relative contributions to observed differences from concentration-dependent
toxicokinetics and interindividual and interoccasion variability remain to be
determined.
PMID- 17032702
TI - Brain manganese accumulation is inversely related to gamma-amino butyric acid
uptake in male and female rats.
AB - Iron (Fe) is an essential trace metal involved in numerous cellular processes.
Iron deficiency (ID) is reported as the most prevalent nutritional problem
worldwide. Increasing evidence suggests that ID is associated with altered
neurotransmitter metabolism and a risk factor for manganese (Mn) neurotoxicity.
Though recent studies have established differences in which the female brain
responds to ID-related neurochemical alterations versus the male brain, little is
known about the interactions of dietary ID, Mn exposure, and sex on gamma-amino
butyric acid (GABA). Male and female Sprague-Dawley rats were randomly divided
into four dietary treatment groups: control (CN), control/Mn supplemented, ID,
and ID/Mn supplemented. After 6 weeks of treatment, both ID diets caused a highly
significant decrease in Fe concentrations across all brain regions compared to CN
in both sexes. Both ID and Mn supplementation led to significant accumulation of
Mn across all brain regions in both sexes. There was no main effect of sex on Fe
or Mn accumulation. Striatal synaptosomes were utilized to examine the effect of
dietary intervention on (3)H-GABA uptake. At 4 weeks, there was a significant
correlation between Fe concentration and (3)H-GABA uptake in male rats (p <
0.05). At 6 weeks, there was a significant inverse correlation between Mn
concentration and (3)H-GABA uptake in male and female rats and a postitive
correlation between Fe concentration and (3)H-GABA uptake in female rats (p <
0.05). In conclusion, ID-associated Mn accumulation is similar in both sexes,
with Mn levels affecting GABA uptake in both sexes in a comparable fashion.
PMID- 17032703
TI - Goal setting frequency and the use of behavioral strategies related to diet and
physical activity.
AB - Goal setting is an effective way to focus attention on behavior change.
Theoretically, frequency of goal setting may indicate the level of commitment to
diet and physical activity behavior change. Yet, little is known about the
association between goal setting frequency and use of specific diet or physical
activity-related strategies. This study examines whether changes in goal setting
frequency predict changes in use of behavioral strategies over time, controlling
for baseline strategy use, demographics and whether a person was trying to lose
weight. Data are from a baseline and 1-year follow-up survey of adults in rural
Iowa (n = 385). Overall, goal setting frequency was positively associated with
use of the strategies measured, at baseline and overtime. Frequent goal setting
that is focused specifically on diet or physical activity was more predictive of
using dietary or physical activity strategies, respectively, than goal setting
focused on weight loss overall. The study provides empirical support for what has
been assumed theoretically, that is, frequent goal setting for weight management
is an indicator of use of specific behavioral strategies. Significant challenges
remain in regard to maintenance of this activity and attainment of weight loss
goals.
PMID- 17032704
TI - Evaluation of a 2-year physical activity and healthy eating intervention in
middle school children.
AB - The aim of the present study was to evaluate the effects of a middle school
physical activity and healthy eating intervention, including an environmental and
computer-tailored component, and to investigate the effects of parental
involvement. A random sample of 15 schools with seventh and eight graders was
randomly assigned to one of three conditions: (i) intervention with parental
involvement, (ii) intervention alone and (iii) control group. In 10 schools, an
intervention, combining environmental changes with computer-tailored feedback,
was implemented over 2 school years. In five intervention schools, increased
parental support was added. Physical activity was measured with questionnaires in
the total sample and with accelerometers in a sub-sample of children. Fat intake,
fruit, water and soft drink consumption were measured using food-frequency
questionnaires. Results showed significant positive intervention effects on
physical activity in both genders and on fat intake in girls. Parental
involvement did not increase intervention effects. It can be concluded that
physical activity and eating behaviours of middle school children can be improved
by school-based strategies combining environmental and personal interventions.
The use of personalized computer-tailored interventions seems to be a promising
tool for targeting adolescents but needs to be further explored.
PMID- 17032705
TI - Effects of tailoring health messages on physical activity.
AB - Computer-tailored printed education can be a promising way of promoting physical
activity. The present study tested whether computer-tailored feedback on physical
activity is effective and whether there are differences between respondents with
low and high motivation to change. Respondents (n = 487) were randomly assigned
to a tailored intervention group or a no information control group. Physical
activity and determinants were measured at baseline and after 3 months. At post
test, the motivated respondents in the control group were more likely not to meet
the recommendation for physical activity than to meet it, and motivated
respondents in the experimental group were more likely to engage in transport
related activities and showed more improvement over time for the total activity
score than respondents in the control group (beta = 0.24, P = 0.02). Both groups
improved their behaviour over time. No group differences in physical activity
were found for the unmotivated respondents. The results showed that the effects
of the tailored feedback were restricted to respondents who had a positive
motivation to change at baseline. Possible explanations could be that unmotivated
respondents were unwilling to read and process the information because they felt
'no need to change'. Alternatively, one tailored feedback letter may not have
been sufficient for this unmotivated group.
PMID- 17032706
TI - Is parenting style related to children's healthy eating and physical activity in
Latino families?
AB - Parenting styles influence a child's risk for obesity. The goals of this study
are to evaluate the influence of (i) parenting style on children's health
behaviors (physical activity and dietary intake), (ii) children's
sociodemographic characteristics on parenting style and on children's health
behaviors and (iii) parents' sociodemographic characteristics on their use of
controlling styles to promote a healthy home environment. Survey and
anthropometric data were collected from a community sample of Latino parents (n =
812) and their children in kindergarten through second grade. Parental use of
positive reinforcement and monitoring was associated with children's healthy
eating and exercise. Also, parents' use of appropriate disciplining styles was
associated with healthier eating, while parental use of control styles was
associated with unhealthy eating. The daughters of parents who used controlling
styles ate more unhealthy foods than did the sons. Older, employed and more
acculturated parents used less controlling styles than their counterparts.
Parenting interventions targeting children's dietary intake and physical activity
should encourage parents to use more positive reinforcement and monitor their
children's health behaviors as these parenting styles are associated with
healthier behaviors. Moreover, intervention researchers may want to encourage
Latino parents to use less controlling styles with girls as this parenting style
increased girls' risk for unhealthy eating.
PMID- 17032707
TI - Evaluation of the training of Korean community health workers for chronic disease
management.
AB - The use of community health workers (CHWs) or lay health advisors has been
increasingly popular as an effective means of secondary prevention for
cardiovascular health in hard-to-reach, underserved populations. Yet, published
evaluations of the CHW training programs are rare. The purpose of this article is
to report the results of an evaluation of a CHW training program for hypertension
and diabetes management for Korean-American seniors. Forty-eight hours of
training was developed and delivered to 12 Korean CHWs. Evaluation of the
training program involved CHW surveys, trainer observation and debriefing and CHW
focus groups. Testing of CHW knowledge showed that all CHWs met the minimum
required knowledge level of 70%. Independent ratings by two trainer observations
revealed that the overall CHW performance was satisfactory. Both CHW ratings and
focus group data indicated that the training program met their expectation
(average 9.3 on a 10-point scale) and was successful in empowering them to assume
their role as a 'health initiator', 'health advertising agent' or 'health role
model'. While this course is judged to be effective in general, future research
is warranted to determine whether CHW provision of care and support will affect
health outcomes in the target population.
PMID- 17032708
TI - Health promotion for people with disabilities: development and evaluation of the
Living Well with a Disability program.
AB - People with disabilities can benefit from health promotion opportunities to
reduce the incidence and severity of secondary conditions that further limit
their participation in society. This paper describes participatory action
research (PAR) methods we used to develop, implement and evaluate the Living Well
with a Disability program. Community-based agencies that provide information and
referral services to people with disabilities (independent living centers funded
under Title VII, Rehabilitation Act) recruited a convenience sample of 246 people
with mobility impairments to participate in a randomly assigned, wait-list
control health promotion intervention study. Paper-and-pencil outcome measures
included the secondary conditions surveillance instrument, unhealthy days and
health care utilization. Logistic regression on outcomes controlling for
demographic variables and pre-test measures indicated reductions in all three
outcome variables. People with mobility impairments who participated in the
Living Well with a Disability program reported less limitation from secondary
conditions, fewer unhealthy days and less health care utilization. PAR methods
are particularly important to design useful interventions for this population.
PMID- 17032710
TI - The somatotopic organization of cytoarchitectonic areas on the human parietal
operculum.
AB - The secondary somatosensory cortex (SII) of nonhuman primates is located on the
parietal operculum. In the monkey, electrophysiological and connectivity tracing
studies as well as histological investigations provide converging evidence for 3
distinct cortical areas (SII, PV, and VS) within this region, each of which
contains a complete somatotopic map. Although the equivalency of the parietal
operculum as the location of SII between humans and nonhuman primates is
undisputed, the internal organization of the human SII region is still largely
unknown. Based on their topography, we have previously argued that the
cytoarchitectonic areas OP 1, OP 4, and OP 3 may constitute the human homologues
of areas SII, PV, and VS, respectively. To test this hypothesis, we here examined
(using functional magnetic resonance imaging) the somatotopic organization of the
human parietal operculum by applying tactile stimulation to the skin at 4
different locations on either side of the body (face, hands, trunk, and legs).
The locations of the resulting activation foci were then compared with the
cytoarchitectonic maps of this region. Data analysis revealed 2 somatotopic body
representations on the lateral operculum in areas OP 1 and OP 4. The functional
border between these 2 body maps was defined by a mirror reversal in the
somatotopic arrangement and coincided with the cytoarchitectonically defined
border between these 2 areas. This somatotopic arrangement closely matches that
described for SII and PV in nonhuman primates. The data also suggested a third
somatotopic map located deeper inside the Sylvian fissure in area OP 3. Based on
the observed topographic arrangement and their functional response
characteristics, we conclude that cytoarchitectonic areas OP1, OP 4, and OP 3 on
the human parietal operculum constitute the human homologues of primate areas
SII, PV, and VS, respectively.
PMID- 17032711
TI - Thyroid hormone signaling in human ovarian surface epithelial cells.
AB - CONTEXT: Ovarian surface epithelial (OSE) cells express multiple nuclear hormone
receptor genes, including those encoding thyroid hormone and estrogen receptors
(TR and ER, respectively). Ovarian cancer is hormone-dependent, and
epidemiological evidence links hyperthyroidism, inflammation of the ovarian
surface, and increased risk of ovarian cancer. OBJECTIVE: The objective of this
study was to assess T3 action on human OSE cells in vitro, asking 1) is there
evidence for (pre)receptor control, 2) is T3 inflammatory, and 3) does T3 affect
ER expression? DESIGN: Immunohistochemical analysis of fixed human ovaries and in
vitro analysis of human OSE primary cell cultures were performed. PATIENTS:
Twelve women aged 29-50 yr (median, 41 yr) undergoing elective gynecological
surgery for nonmalignant conditions were studied. RESULTS: Messenger RNA
transcripts for TRalpha1, TRalpha2, TRbeta1, and T3 activating deiodinase 2 and
inactivating deiodinase 3 were present in primary OSE cell cultures by RT-PCR.
TRalpha and TRbeta proteins were also localized to intact OSE by
immunohistochemistry. Treatment of OSE cell cultures for 24 h with T3 caused dose
dependent mRNA expression of inflammation-associated genes: cyclooxygenase-2,
matrix metalloproteinase-9, and 11betahydroxysteroid dehydrogenase type 1,
determined by quantitative RT-PCR. Finally, treatment with T3 dose dependently
stimulated ERalpha mRNA expression without affecting ERbeta1 or ERbeta2.
CONCLUSION: The ovarian surface is a potential T3 target. T3 exerts direct
inflammatory effects on OSE cell function in vitro. OSE cell responses to T3
include increased expression of ERalpha mRNA, which encodes the ER isoform most
strongly associated with ovarian cancer. This could help explain suggested
epidemiological links between hyperthyroidism and ovarian cancer.
PMID- 17032712
TI - An age-related decrease in creatinine clearance is associated with an increase in
number of falls in untreated women but not in women receiving calcitriol
treatment.
AB - CONTEXT: Decreased calcitriol production due to impaired renal function may be a
significant risk factor for falls in normal aging population. OBJECTIVE: The
objective of the study was to examine the association between creatinine
clearance (CrCl) and the incidence of falls and fallers in groups treated with
placebo, calcitriol, estrogen therapy (ET)/estrogen + progestin therapy (HT), and
calcitriol + ET/HT. DESIGN: This was a 3-yr, double-blind, placebo-controlled
study designed to test the efficacy of calcitriol and ET/HT on bone loss and
falls with analysis by intention to treat and post hoc. SETTING: The study was
conducted at an academic outpatient center. PARTICIPANTS: Four hundred eighty
nine normal elderly women aged 65-77 yr; 415 women completed the study.
INTERVENTION: Subjects were randomized to placebo, calcitriol 0.25 mug twice a
day, ET daily (conjugated equine estrogens 0.625 mg), HT (conjugated equine
estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg) and calcitriol + ET/HT.
MAIN OUTCOME MEASURES: Cumulative number of falls and fallers were compared
between groups with 24-h urine CrCl less than 60 and 60 ml/min or greater.
RESULTS: Calcitriol treatment decreased the number of fallers and falls. Low CrCl
less than 60 ml/min was a predictor of the number of falls per person but not
fallers in the placebo group (P = 0.007). In the low CrCl group (<60 ml/min), the
rate of falls decreased on calcitriol by 53% [95% confidence interval (CI) -71%
to -22%; P = 0.003], calcitriol + ET/HT by 61% (95% CI -76% to -37%; P = 0.001),
and ET/HT by 25% (95% CI: -55% to +24%; not significant). Calcitriol reduced the
rate of falls by 30% (95% CI -49% to -4%; P = 0.027) in the CrCl 60 ml/min or
greater group. CONCLUSION: Calcitriol treatment decreases falls in all subjects
but especially in elderly women with decreased renal function (<60 ml/min) and
frequent fallers.
PMID- 17032713
TI - Detection of thyroid dysfunction in early pregnancy: Universal screening or
targeted high-risk case finding?
AB - CONTEXT: Maternal subclinical hypothyroidism during pregnancy is associated with
various adverse outcomes. Recent consensus guidelines do not advocate universal
thyroid function screening during pregnancy but recommend testing high-risk
pregnant women with a personal history of thyroid or other autoimmune disorders
or with a family history of thyroid disorders. OBJECTIVE: The objective of the
study was to assess efficacy of the targeted high-risk case-finding approach in
identifying women with thyroid dysfunction during early pregnancy.
DESIGN/SETTING: This was a single-center cohort study. PATIENTS/OUTCOME MEASURES:
We prospectively analyzed TSH, free T4 and free T3 in 1560 consecutive pregnant
women during their first antenatal visit (median gestation 9 wk). We tested
thyroperoxidase antibodies in 1327 (85%). We classified 413 women (26.5%), who
had a personal history of thyroid or other autoimmune disorders or a family
history of thyroid disorders, as a high-risk group. We examined whether testing
only such a high-risk group would pick up most pregnant women with thyroid
dysfunction. RESULTS: Forty women (2.6%) had raised TSH (>4.2 mIU/liter). The
prevalence of raised TSH was higher in the high-risk group [6.8 vs. 1% in the low
risk group, relative risk (RR) 6.5, 95% confidence interval (CI) 3.3-12.6, P <
0.0001]. Presence of personal history of thyroid disease (RR 12.2, 95% CI 6.8-22,
P < 0.0001) or other autoimmune disorders (RR 4.8, 95% CI 1.3-18.2, P = 0.016),
thyroperoxidase antibodies (RR 8.4, 95% CI 4.6-15.3, P < 0.0001), and family
history of thyroid disorders (RR 3.4, 95% CI 1.8-6.2, P < 0.0001) increased the
risk of raised TSH. However, 12 of 40 women with raised TSH (30%) were in the low
risk group. CONCLUSION: Targeted thyroid function testing of only the high-risk
group would miss about one third of pregnant women with overt/subclinical
hypothyroidism.
PMID- 17032714
TI - The ghrelin response to exercise before and after growth hormone administration.
AB - CONTEXT: We have previously shown that exercise-induced GH release is not
mediated by ghrelin, but it remains to be studied whether the increase in GH may
suppress postexercise ghrelin levels. OBJECTIVE: The objective of this study was
to characterize systemic ghrelin levels after exercise with and without
concomitant GH administration. DESIGN, PARTICIPANTS, AND INTERVENTION: Group A:
Twenty-nine elite athletes (age, 18-37 yr) were studied after a maximal exercise
test. Group B: In a double blind, placebo-controlled, parallel study, 32 healthy
subjects (age, 18-33 yr) were randomized to placebo, GH 0.1 IU/kg per day, or GH
0.2 IU/kg per day for 4 wk. These subjects performed a multistage fitness test to
assess maximum oxygen uptake at baseline and after 4 wk. We measured total
circulating ghrelin levels before and immediately after exercise and at 15, 30,
60, 90, and 120 min after exercise. RESULTS: Group A: Serum ghrelin levels after
exercise decreased significantly (P < 0.01). Group B: Exercise at baseline was
associated with a significant lowering of ghrelin levels after exercise (P <
0.0001). In addition, 4 wk of high-dose GH were followed by a further
approximately 20% reduction in basal and after exercise serum ghrelin (micrograms
per liter): 0.78 (range 0.52-1.17) vs. 0.63 (range 0.50-0.91), P < 0.05.
CONCLUSIONS: 1) Ghrelin levels decrease significantly after exercise in elite
athletes and healthy subjects. 2) High-dose GH suppresses ghrelin levels. 3)
These data support the hypothesis that GH feedback inhibits ghrelin secretion.
PMID- 17032715
TI - Mild gestational diabetes as a risk factor for congenital cryptorchidism.
AB - CONTEXT: Cryptorchidism is the most common malformation in newborn boys. Maternal
diabetes has previously been suggested to be a risk factor for this disorder in
one epidemiological study. OBJECTIVE: Evaluation of the prevalence of maternal
glucose metabolism disorders during pregnancy in newborn boys having normal
testicular descent or congenital cryptorchidism. DESIGN: Postnatal analysis of
maternal history concerning glucose metabolism abnormalities during pregnancy
among cryptorchid and healthy Finnish boys. SETTING AND PARTICIPANTS: The
material of this case-control study comprises 1163 boys with normal testicular
descent at birth and 125 boys with congenital cryptorchidism. All these singleton
Finnish boys were born in Turku University Central Hospital (1997-2001) and were
examined at birth and/or at the expected date of delivery. MAIN OUTCOME MEASURES:
Information about maternal diabetes diagnosis and abnormality of the result of a
2-h 75-g oral glucose tolerance test during pregnancy were obtained from the
hospital records after delivery. RESULTS: After adjustment for possible
confounding factors, i.e. maternal smoking during pregnancy, maternal age at
delivery, and risk factors of cryptorchidism, e.g. prematurity and weight for
gestational age, abnormal maternal glucose metabolism was significantly more
common in the group of cryptorchid boys [diet-treated gestational diabetes, P =
0.0001; odds ratio, 3.98 (95% confidence interval, 1.97-8.05); diet-treated
gestational diabetes or only an abnormal result in oral glucose tolerance test, P
= 0.0016; odds ratio, 2.44 (95% confidence interval, 1.40-4.25)] when compared
with boys with normal testicular descent. CONCLUSIONS: Mildly abnormal glucose
metabolism during pregnancy was associated with an increased risk for congenital
cryptorchidism. The mechanism remains to be elucidated.
PMID- 17032716
TI - Effectiveness of bone density measurement for predicting osteoporotic fractures
in clinical practice.
AB - CONTEXT: Bone density measurement with dual-energy x-ray absorptiometry is widely
used for fracture risk assessment. It has not been established that published
gradients of fracture risk from study populations can be directly applied to
clinical populations. OBJECTIVE: The objective of the study was to assess
osteoporotic fracture prediction with dual-energy x-ray absorptiometry in a large
clinical cohort. DESIGN: This was a historical cohort study (mean observation
period 3.2 +/- 1.5 yr). PATIENTS: The study population was drawn from the
population-based database of the Manitoba Bone Density Program. Analyses were
limited to women aged 50 yr or older at baseline (n = 16,505). MAIN OUTCOME
MEASURE: Each subject's longitudinal health service record was assessed for the
presence of nontrauma fracture codes (hip, spine, wrist, and humerus) after bone
density testing. Age-adjusted hazard ratios for fracture were derived from Cox
proportional hazards models. RESULTS: Site-specific and overall fracture rates
were significantly associated with each site of bone density measurement (all P <
0.00001). The 95% confidence intervals overlapped those from a widely cited
metaanalysis of fracture prediction from different sites. Although fracture
prediction was not significantly different between the three hip measurement
sites, each hip site was better than the lumbar spine for predicting overall
fractures (nonoverlapping 95% confidence intervals). The manufacturer sd
(equivalent to a unit change in T-score) resulted in a significantly smaller
gradient of risk for the spine than when the population sd was used. CONCLUSIONS:
Bone density measurements are effective for predicting fractures in clinical
practice. However, hip measurements were superior to the spine in overall
osteoporotic fracture prediction.
PMID- 17032717
TI - Metabolic profile and body composition in adult women with congenital adrenal
hyperplasia due to 21-hydroxylase deficiency.
AB - CONTEXT: The chronic, often supraphysiological glucocorticoid doses used in
congenital adrenal hyperplasia (CAH) might increase morbidity in cardiovascular
disease and diabetes. OBJECTIVE: Our aim was to assess risk factors for
cardiovascular disease and diabetes in CAH women. SUBJECTS, METHODS, AND DESIGN:
We compared 61 women, 18-63 yr, with CAH due to 21-hydroxylase deficiency with 61
age- and sex- matched controls. Twenty-seven were younger than 30 yr, and 34 were
30 yr or older. Anthropometry, fat and lean mass measured by dual-energy x-ray
absorptiometry, serum lipids, insulin, and adrenocortical steroids were studied.
MAIN OUTCOME MEASURE: Body composition and cardiovascular risk factors were the
main outcome measures. RESULTS: Younger patients and controls had similar waist
to hip ratio, lean and fat mass, and insulin. Older patients had higher waist to
hip ratio, lean mass, and insulin than controls. Fat mass was similar to controls
but higher than in younger patients. Lipid profiles were slightly more favorable
in older patients than controls. Gestational diabetes was more common in patients
(21% of pregnancies vs. 0, P < 0.026). Few older patients had hypertension,
cardiovascular disease, or diabetes. Despite moderate glucocorticoid doses, most
patients had suppressed androgens. CONCLUSIONS: No clear evidence of unfavorable
cardiovascular risk factors were found. Increased fat mass and higher insulin
levels were, however, found in patients older than 30 yr. High frequency of
gestational diabetes is a risk marker for future diabetes. Lifelong follow-up,
lifestyle modifications, and attempts to adjust and reduce the glucocorticoid
doses seem important.
PMID- 17032718
TI - 131I activity for remnant ablation in patients with differentiated thyroid
cancer: A systematic review.
AB - CONTEXT: Radioiodine ablation of the thyroid remnant after thyroidectomy is
commonly performed in the management of patients with differentiated thyroid
cancer. Although many centers administer an activity of 100 mCi, there is
uncertainty over using a lower activity. OBJECTIVE: A systematic review of the
published literature was used to compare the success rates of remnant ablation
using approximately 30 mCi with approximately 100 mCi (1.1 vs. 3.7 GBq). DATA
SOURCES: Data were obtained from MEDLINE and EMBASE for the years 1966 to March
2006. STUDY SELECTION: All studies that reported rates of successful ablation
associated with approximately 30 or approximately 100 mCi of radioiodine were
reviewed. DATA EXTRACTION: Studies were based on reviews of patient case notes (n
= 41), prospective cohorts (n = 12), and randomized trials (n = 6). We obtained
the success of thyroid remnant ablation according to different administered
activities of radioiodine. Where a study reported on two or more activities, the
risk ratio of having a successful ablation (approximately 30 vs. approximately
100 mCi) was calculated and combined in a meta-analysis. DATA SYNTHESIS:
Observational studies confirmed the high ablation success rate ( approximately
80%) using approximately 100 mCi, although 22% of studies reported a rate of 90%
or greater. The pooled ablation success rate in these studies was 10% lower using
30 mCi compared with 100 mCi (95% confidence interval, 3-17%; P = 0.01). The meta
analysis of the randomized trials produced equivocal results. For example, the
rate of successful ablation in patients given 30 mCi was 8% lower compared with
100 mCi (95% confidence interval, 29% lower or up to 20% greater, P = 0.58),
consistent with there being no difference or that 30 mCi is much less effective.
CONCLUSIONS: From the published data, it is not possible to reliably determine
whether ablation success rates using 30 mCi are similar to using 100 mCi. Large
randomized trials are needed to resolve the issue and guide clinical practice.
PMID- 17032719
TI - Vascular endothelial cadherin regulates vascular permeability: Implications for
ovarian hyperstimulation syndrome.
AB - CONTEXT: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication
of treatment with fertility drugs. It is characterized by increased vascular
permeability and simultaneous overexpression of vascular endothelial growth
factor (VEGF) in ovarian cells. OBJECTIVE: We tested the hypothesis that the
endothelium and endothelial cell-to-cell junctions are downstream targets of VEGF
during OHSS pathogenesis. We investigated the potential involvement of vascular
endothelial (VE)-cadherin, an interendothelial adhesion molecule, in the
capillary hyperpermeability in OHSS. DESIGN: Human endothelial cells from
umbilical veins (HUVEC) were used as an in vitro model of OHSS. INTERVENTION:
Cell cultures were treated with varying doses of estradiol (E2), human chorionic
gonadotropin (hCG), VEGF, and antihuman VEGF antibodies, either alone or in
combination, and the effect on VE-cadherin release was evaluated at different
time points. Permeability assays were performed using fluoresceinisothiocyanate
labeled albumin, and actin filaments rearrangement was evaluated by fluorescent
microscopy. RESULTS: Culturing of HUVEC with high doses of E2 produced no
significant changes in VE-cadherin concentration, but hCG and VEGF produced a
significant increase in VE-cadherin release. Time-course experiments showed that
VE-cadherin was secreted 12 h after VEGF addition. Antihuman VEGF antibodies
prevented these changes. Permeability assays demonstrated that, although E2 did
not alter the arrangement of HUVEC in vitro, hCG and VEGF caused changes in the
actin fibers indicative of increased capillary permeability. VEGF also induced an
increase in paracellular permeability of HUVEC at the same doses used in the
previous experiments. CONCLUSIONS: Adhesion molecules like VE-cadherin may play a
role in the development and progression of increased capillary permeability in
severe OHSS.
PMID- 17032720
TI - Prematurity may be a risk factor for thyroid dysfunction in childhood.
AB - CONTEXT: Children born prematurely and/or small for gestational age (SGA)
frequently show disturbances in thyroid function. OBJECTIVE: The objective of the
study was to determine the role played either by size or gestational age on
subsequent thyroid function. DESIGN AND SETTING: This cross-sectional study was
conducted at a tertiary referral hospital. PATIENTS: A total of 117 children, 88
of whom were SGA (mean age 7.8 +/- 2.5 yr) and 29 appropriate for gestational age
(AGA) (mean age 8.1 +/- 1.9 yr), were selected for the study. MAIN OUTCOME
MEASURES: We evaluated TSH, free T(4), free T(3), urinary iodine, and antithyroid
antibodies, and all patients underwent a thyroid ultrasound. Insulin sensitivity
was assessed with the quantitative insulin sensitivity check index. RESULTS: TSH
and free T3 were not significantly different in the two groups, whereas free T4
was higher in the AGA group (P < 0.005). Interestingly, four AGA (13.8%) and 17
SGA (19.3%) patients had TSH levels above the upper limit of normality. Thyroid
volume was normal and thyroid autoimmunity was excluded. Urinary iodine was also
similar in the two groups (115 +/- 66 vs. 143 +/- 87); however, in both groups
there were some children [15 AGA (51%) and 13 SGA (14.7%) (P < 0.001)] with a
mild to moderate iodine deficiency. By multiple regression analysis, gestational
age was found to be the only determinant of TSH serum levels. Insulin sensitivity
was the same in both groups of children and similar to controls. CONCLUSIONS:
Some children born prematurely, independently from their birth size, frequently
have disturbances of the hypothalamus-pituitary-thyroid axis later in life.
PMID- 17032721
TI - Haplotypes in the lipoprotein lipase gene influence fasting insulin and discovery
of a new risk haplotype.
AB - CONTEXT: Prior studies of Mexican Americans described association of lipoprotein
lipase (LPL) gene haplotypes with insulin sensitivity/resistance and
atherosclerosis. The most common haplotype (haplotype 1) was protective, whereas
the fourth most common haplotype (haplotype 4) conferred risk for insulin
resistance and atherosclerosis. OBJECTIVE: In this study of Hispanics in the
Insulin Resistance Atherosclerosis Study Family Study, we sought to replicate LPL
haplotype association with insulin sensitivity/resistance. DESIGN: LPL haplotypes
based on 12 single nucleotide polymorphisms were analyzed for association with
indexes of insulin sensitivity and other metabolic and adiposity measures.
SETTING: This study was conducted in the general community of San Antonio, Texas,
and San Luis Valley, Colorado. PARTICIPANTS: Participants in this study were 978
members of 86 Hispanic families. MAIN OUTCOME MEASURES: LPL haplogenotype,
metabolic phenotypes, and adiposity were measured in this study. RESULTS: The
haplotype structure was identical with that observed in prior studies. Among 978
phenotyped subjects, haplotype 1 was associated with decreased fasting insulin (P
= 0.01), and haplotype 4 was associated with increased fasting insulin (P = 0.02)
and increased visceral fat mass (P = 0.002). Insulin sensitivity, derived from iv
glucose tolerance testing, tended (P > 0.1) to be higher with haplotype 1 (S(I) =
1.72) and lower with haplotype 4 (S(I)=1.38). Haplotype 2 was associated with
increases in fasting insulin, triglycerides (TGs), TG to high-density lipoprotein
cholesterol ratio, and apolipoprotein B (P = 0.01-0.04). CONCLUSIONS: This study
independently replicates our prior results of LPL haplotypes 1 and 4 as
associated with measures of insulin sensitivity and resistance, respectively.
Haplotype 4 may confer insulin resistance by increasing visceral fat. Haplotype 2
was identified as a new risk haplotype, suggesting the complex nature of LPL's
effect on features of the insulin resistance syndrome.
PMID- 17032722
TI - Association of weight gain in infancy and early childhood with metabolic risk in
young adults.
AB - CONTEXT: Early postnatal life has been suggested as an important window during
which risks for long-term health may be influenced. OBJECTIVE: The aim of this
study was to examine the independent associations between weight gain during
infancy (0-6 months) and early childhood (3-6 yr) with components of the
metabolic syndrome in young adults. DESIGN: This was a prospective cohort study
(The Stockholm Weight Development Study). SETTING: The study was conducted in a
general community. PARTICIPANTS: Subjects included 128 (54 males) singletons,
followed from birth to 17 yr. MAIN OUTCOME MEASURE: None of these young adults
met the full criteria for the metabolic syndrome. We therefore calculated a
continuous clustered metabolic risk score by averaging the standardized values of
the following components: waist circumference, blood pressure, fasting
triglycerides, high-density lipoprotein cholesterol, glucose, and insulin level.
RESULTS: Clustered metabolic risk at age 17 yr was predicted by weight gain
during infancy (standardized beta = 0.16; P < 0.0001) but not during early
childhood (standardized beta = 0.10; P = 0.23), adjusted for birth weight,
gestational age, current height, maternal fat mass, and socioeconomic status at
age 17 yr. Further adjustment for current fat mass and weight gain during
childhood did not alter the significant association between infancy weight gain
with the metabolic risk score (standardized beta = 0.20; P = 0.007). CONCLUSIONS:
Rapid weight gain during infancy (0-6 months) but not during early childhood (3-6
yr) predicted clustered metabolic risk at age 17 yr. Early interventions to
moderate rapid weight gain even at very young ages may help to reduce adult
cardiovascular disease risks.
PMID- 17032723
TI - Aldosterone-to-renin ratio as a marker for disease severity in 21-hydroxylase
deficiency congenital adrenal hyperplasia.
AB - CONTEXT: Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency
(21 OHD) is classified clinically in decreasing order of severity into salt
wasting, simple-virilizing, and nonclassical forms. Causative mutations in the
CYP21A2 gene dictate the degrees of adrenal enzyme defect. Salt-wasting crises
due to aldosterone deficiency are clinically apparent in the salt-wasting form
but not in other forms of 21 OHD. OBJECTIVES: This study examined the ratio of
serum aldosterone to plasma renin activity as an index of sodium wasting in
patients with 21 OHD CAH, heterozygotes, and normal individuals. DESIGN: This was
a cross-sectional, retrospective, noninterventional study. PATIENTS AND OTHER
PARTICIPANTS: A total of 402 individuals were included: 224 patients affected
with 21 OHD CAH and 178 unaffected subjects. Classification into each diagnostic
group was made primarily on the basis of clinical and hormonal features. Affected
or unaffected status was confirmed by genotype of CYP21A2. All subjects were on
ad lib diets without restrictions. Salt-wasting status was examined by sodium
deprivation testing in 32 salt-wasting subjects and 14 simple virilizing
subjects. RESULTS: The ratio of serum aldosterone to plasma renin activity was
found to discriminate well between the different groups of disease severity. The
lowest ratios, indicative of the least sodium conservation, were seen in the salt
wasting group with increasing ratios in the simple virilizing, nonclassical, and
unaffected groups. This ratio remained stable with age. CONCLUSION: The ratio of
serum aldosterone to plasma renin activity provides a simple index to compare
groups of patients with varying degrees of 21 OHD.
PMID- 17032725
TI - A common mitochondrial DNA variant and increased body mass index as associated
factors for development of type 2 diabetes: Additive effects of genetic and
environmental factors.
AB - OBJECTIVE: The suggested correlation between a T-to-C transition at the
nucleotide 16189 in mitochondrial DNA (mtDNA) with increasing insulin resistance
and adult-onset diabetes mellitus (DM) is debatable. METHODS: Our study examined
mtDNA from 462 subjects with type 2 diabetes (T2DM) and 592 normoglycemic
controls (non-DM). Each participant's body mass index (BMI), fasting plasma
glucose, fasting insulin concentration, insulin resistance index, and beta-cell
function were measured. Sequencing for mtDNA, focusing on exploration of the
hypervariable polycytosine tract within the control region, was also conducted in
all subjects. RESULTS: Prevalence of the mtDNA 16189 variant was significantly
different between DM and non-DM subjects (39.2% vs. 30.7% respectively; P =
0.004). Increased incidence of DM was noted in those harboring the 16189 variant
compared with those lacking the variant (multivariate odds ratio, 1.38; 95%
confidence interval, 1.07-1.80). Moreover, increased BMI was identified as an
aggravating factor for development of DM in subjects harboring the variant. Odds
ratio determinations yielded 2.14 in overweight and 4.63 in obese subjects
harboring the variant in comparison with subjects without (1.83 in overweight and
2.16 in obese subjects). This is consistent with a progressively increased
prevalence of the mtDNA 16189 variant in the non-DM groups with higher fasting
insulin concentration, insulin resistance index, and beta-cell function (all
P(trend) < 0.005). CONCLUSION: The mtDNA 16189 variant can influence development
of T2DM. The demonstrated dynamic between the 16189 variant and increased BMI
exemplify an additive effect of genetic and environmental factors on the
pathogenesis of T2DM.
PMID- 17032724
TI - Dopamine receptor expression and function in corticotroph ectopic tumors.
AB - BACKGROUND: Dopamine receptor (DR) expression and dopamine agonist (DA)
effectiveness have never been demonstrated in neuroendocrine tumors associated
with ectopic ACTH syndrome (EAS). AIM: The aim of the current study was to
evaluate DR and particularly D2 subtype expression in neuroendocrine tumors
associated with EAS and to evaluate the in vivo effectiveness of the DA
cabergoline in the treatment of EAS. PATIENTS AND METHODS: Six ACTH-secreting
neuroendocrine tumors, including four lung, one pancreatic, and one thymic
carcinoid, were used for the evaluation of D2 expression by immunohistochemistry.
DR subtypes and D2 isoforms and number were evaluated by RT-PCR in three cases of
persistent EAS after surgery. These patients were treated with cabergoline at the
dose of 3.5 mg/wk for 6 months. Clinical parameters, hormonal levels, and tumor
size were monitored during the treatment period. RESULTS: At
immunohistochemistry, D2 was expressed in five (83.3%) tumors. At RT-PCR, D2 was
confirmed in all three cases but at variable numbers, whereas D4 was expressed in
two cases. D(2long) was expressed in all three cases, together with D(2short) in
one case. A normalization of urinary cortisol levels was found in two patients
(66.7%) after 3 months of treatment. However, treatment escape was demonstrated
in one of these patients afterward. CONCLUSION: The results of this study
demonstrated that DR are expressed in neuroendocrine tumors associated with EAS
and that cabergoline treatment could be effective in controlling cortisol excess
in a subgroup of patients with EAS. Further studies on a larger number of
patients are mandatory to confirm the usefulness of DA in EAS.
PMID- 17032726
TI - Thyroid hormone increases mRNA and protein expression of Na+-K+-ATPase alpha2 and
beta1 subunits in human skeletal muscles.
AB - CONTEXT: Thyroid hormone regulates specific Na+-K+-ATPase isoforms in rodent
skeletal muscles. No study has examined this relationship in human tissues.
OBJECTIVE: This study investigated the effect of hyperthyroid status on the
expression of the alpha- and beta-subunits of the Na+-K+-ATPase. DESIGN: The
vastus lateralis muscles from eight hyperthyroid patients were biopsied before
and after treatment. Ten age-matched euthyroid subjects served as controls.
RESULTS: In hyperthyroid patients, the average T3 level was three times higher in
pretreatment compared with posttreatment (262 +/- 75 vs. 86 +/- 21 ng/dl, P =
0.001). The relative mRNA expression of the alpha2, but not alpha1 or alpha3,
subunit was increased approximately 3-fold in pretreatment (2.98 +/- 0.52 vs.
0.95 +/- 0.40, P < 0.01), whereas that of beta1, not beta2 or beta3, subunit was
increased approximately 2.8-fold in pretreatment (2.83 +/- 0.38 vs. 1.10 +/-
0.27, P < 0.01). The relative mRNA expression of the alpha2 and beta1 subunits
was positively correlated with the serum T3 (r = 0.75, P = 0.001 and r = 0.66, P
= 0.003, respectively). Immunohistochemistry studies revealed an increase in
protein abundance of the alpha2 and beta1, but not alpha1 or beta2, subunits in
the plasma membrane of muscle fibers of hyperthyroid patients, which decreased
after treatment. CONCLUSIONS: This provides the first evidence that, in human
skeletal muscles, thyroid hormone up-regulates the Na+-K+-ATPase protein
expression at least, in part, at mRNA level, and the alpha2 and beta1 subunits
play the important role in this regulation.
PMID- 17032727
TI - Genome-wide patterns of expression in Drosophila pure species and hybrid males.
II. Examination of multiple-species hybridizations, platforms, and life cycle
stages.
AB - Species often produce sterile hybrids early in their evolutionary divergence, and
some evidence suggests that hybrid sterility may be associated with deviations or
disruptions in gene expression. In support of this idea, many studies have shown
that a high proportion of male-biased genes are underexpressed, compared with non
sex-biased genes, in sterile F1 male hybrids of Drosophila species. In this
study, we examined and compared patterns of misexpression in sterile F1 male
hybrids of Drosophila simulans and 2 of its sibling species, Drosophila
mauritiana and Drosophila sechellia, at both the larval and adult life stages. We
analyzed hybrids using both commercial Drosophila melanogaster microarrays and
arrays we developed from reverse transcriptase-polymerase chain reactions of
spermatogenesis and reproduction-related transcripts from these species (sperm
array). Although the majority of misexpressed transcripts were underexpressed, a
disproportionate number of the overexpressed transcripts were located on the X
chromosome. We detected a high overlap in the genes misexpressed between the 2
species pairs, and our sperm array was better at detecting such misexpression
than the D. melanogaster array, suggesting possible weaknesses in the use of an
array designed from another species. We found only minimal misexpression in the
larval samples with the sperm array, suggesting that disruptions in
spermatogenesis occur after this life stage. Further study of these misexpressed
loci may allow us to identify precisely where disruptions in the spermatogenesis
pathway occur.
PMID- 17032728
TI - Characterization of FaRB7, a near root-specific gene from strawberry
(Fragariaxananassa Duch.) and promoter activity analysis in homologous and
heterologous hosts.
AB - Many insect and fungal pathogens posing agronomically important threats
specifically target the roots in strawberry. The use of a root-specific promoter
to confer expression of resistance genes in a targeted manner has the potential
appreciably to benefit the genetic improvement of commercial strawberry
varieties. A novel gene, FaRB7, was isolated from strawberry (Fragariaxananassa
Duch.) and found to contain motifs characteristic of tonoplast intrinsic proteins
(TIPs). Phylogenetic analysis revealed that FaRB7 represents an RB7-type TIP. In
strawberry, this gene is expressed predominantly in roots, with very low
expression in petioles. A 2.843 kb region representing the FaRB7 gene upstream
regulatory sequence was isolated and found to share a number of sequence motifs
with the promoter of the Nicotiana tabacum TobRB7 root-specific RB7-type TIP.
When cloned upstream of the gusA reporter gene and introduced into strawberry
plants, the FaRB7 promoter was shown to direct strong, near root-specific
expression with expression patterns very similar to that of the endogenous gene.
Furthermore, the FaRB7 promoter was found to confer constitutive expression,
comparable to that produced by the cauliflower mosaic virus (CaMV) 35S RNA
promoter, in tobacco. Thus, the FaRB7 promoter may be used to achieve near-root
specific transgene expression in strawberry and also represents an alternative to
the CaMV 35S promoter for producing constitutive foreign gene expression in
heterologous hosts. The FaRB7 full-length genomic sequence and 5' upstream
regulatory region have been submitted to the EMBL/GenBank database under
accession number DQ178022.
PMID- 17032729
TI - Exploring thermal imaging variables for the detection of stress responses in
grapevine under different irrigation regimes.
AB - Temperatures of leaves or canopies can be used as indicators of stomatal closure
in response to soil water deficit. In 2 years of field experiments with
grapevines (Vitis vinifera L., cvs Castelao and Aragones), it was found that
thermal imaging can distinguish between irrigated and non-irrigated canopies, and
even between deficit irrigation treatments. Average canopy temperature was
inversely correlated with stomatal conductance measured with a porometer.
Variation of the distribution of temperatures within canopies was not found to be
a reliable indicator of stress. A large degree of variation between images was
found in reference 'wet' and 'dry' leaves used in the first year for the
calculation of an index proportional to stomatal conductance. In the second year,
fully irrigated (FI) (100% Et(c)) and non-irrigated (NI) canopies were used as
alternatives to wet and dry leaves. A crop water stress index utilizing these FI
and NI 'references', where stressed canopies have the highest values and non
stressed canopies have the lowest values, was found to be a suitable measure for
detecting stress. It is suggested that the average temperatures of areas of
canopies containing several leaves may be more useful for distinguishing between
irrigation treatments than the temperatures of individual leaves. Average
temperatures over several leaves per canopy may be expected to reduce the impact
of variation in leaf angles. The results are discussed in relation to the
application of thermal imaging to irrigation scheduling and monitoring crop
performance.
PMID- 17032730
TI - Low copy number gene transfer and stable expression in a commercial wheat
cultivar via particle bombardment.
AB - Two groups of linear gene constructs (gus and bar, and 1Ax1 and bar) lacking
vector backbone sequences were independently transferred into the elite wheat
(Triticum aestivum L.) variety EM12, and genetically stable transgenic plants
with low copy number transgene integration were recovered. Co-transformation
experiments were carried out in parallel using either circular whole plasmid(s)
or linear gene cassettes which were purified from the same plasmid by restrictive
digestion, each cassette consisting of a promoter, an open reading frame, and a
terminator. Six transgenic wheat lines transformed with 1Ax1 plus bar gene
cassettes, five lines with gus plus bar gene cassettes, three lines with p1Ax1
plus pAHC20, and two lines with pAHC25 were regenerated with transformation
frequencies of 0.6, 0.5, 0.3, and 0.2%, respectively. Southern blotting analysis
showed that there were 1-4 hybridizing bands in transgenic lines carrying gene
cassettes, of which most lines displayed single-copy transgene insertion.
Expression analyses showed that 50.5% of the T1 lines carrying gus plus bar gene
cassettes have the expression signals of two genes. SDS-PAGE analysis of the T1
generation revealed that 71% of herbicide-resistant plants carrying 1Ax1 plus bar
gene cassettes expressed the high molecular weight subunit 1Ax1 in the endosperm.
Gene cassettes were transmitted and segregated in the subsequent generations, in
simple Mendelian ratios. In addition, reverse transcription-polymerase chain
reaction (RT-PCR) results confirmed that 1Ax1 gene cassettes were expressed
specifically in the endosperm of the transgenic wheat plant. It is proposed that
gene transfer using multiple gene cassettes offers an efficient and rapid method
to obtain the single-copy transgenic wheat.
PMID- 17032731
TI - Differential expression within the LOX gene family in ripening kiwifruit.
AB - Real-time quantitative PCR was used to study lipoxygenase (LOX) gene expression
patterns in kiwifruit (Actinidia deliciosa [A. Chev.] C.F. Liang et A.R. Ferguson
var. deliciosa cv. Hayward) during fruit ripening, and in response to ethylene
and low temperature during post-harvest storage. Six LOX genes were identified
and cloned from a kiwifruit EST database. All were expressed in vegetative
tissues and in the fruit. Expression of AdLox1 and AdLox5 increased markedly as
fruit developed to the climacteric stage and were up-regulated by ethylene
treatment, following a similar pattern to LOX enzyme activity. By contrast,
AdLox2, AdLox3, and AdLox4 transcripts were negatively associated with ethylene
accumulation, and ethylene application enhanced the decline in transcript levels.
Transcripts of AdLox6 declined with fruit ripening. The fruit showed no ripening
changes at low temperature, where transcripts of AdLox1 and AdLox6 were slightly
induced about 72 h after harvest, suggesting an adaptive response to low
temperature. Transient expression of the ethylene-responsive AdLox1 gene in
tobacco leaves led to significant degradation of chlorophyll and promoted tissue
senescence, whereas AdLox2 had no such effect. The results showed that the six
LOX genes were differentially regulated during kiwifruit ripening and senescence,
forming two groups, one active in ripening and responsive to ethylene and the
other more constitutively expressed. The possible roles of individual LOX
isoforms in kiwifruit are discussed.
PMID- 17032732
TI - GnRH antagonist-induced inhibition of the premature LH surge increases pregnancy
rates in IUI-stimulated cycles. A prospective randomized trial.
AB - BACKGROUND: Our prospective randomized controlled trial was designed to assess
whether the use of GnRH antagonists can improve the success rate of controlled
ovarian stimulation (COS)/intrauterine insemination (IUI) treatments, via
inhibition of the premature LH rise. METHODS: A total of 104 patients were
randomly divided, using a randomization list, into two groups: in group A (n =
52), recombinant FSH (rFSH) was given with GnRH antagonist Cetrorelix, and in
group B (n = 52), the patients received rFSH alone in a manner similar to that of
group A. The primary outcome measure was clinical pregnancy rate per couple.
RESULTS: The pregnancy rate per patient was 53.8% in group A and 30.8% in group B
(P = 0.017). The rate of premature LH surge was 7% in group A and 35% in group B
(P < 0.0001). A premature luteinization was observed in two cycles of 144 in
group A (1.4%) and in 16 cycles of 154 in group B (10.4%) (P = 0.001). The mean
values of LH and progesterone were significantly lower in patients receiving GnRH
antagonist than in those who did not (3.3 +/- 3.3 mIU/ml in group A versus 9.9 +/
7.9 mIU/ml in group B, P < 0.0001, for LH; 1.3 +/- 1.1 ng/ml versus 2.1 +/- 1.9
ng/ml for group A and B, respectively, P < 0.0001, for progesterone). CONCLUSION:
The use of GnRH antagonist in COS/IUI cycles improves pregnancy rate, preventing
the premature LH rise and luteinization.
PMID- 17032733
TI - S. pombe FEAR protein orthologs are not required for release of Clp1/Flp1
phosphatase from the nucleolus during mitosis.
AB - Cdc14 family phosphatases are highly conserved regulators of cell-cycle
progression. Two of the best studied members of this family are budding yeast
Cdc14p and its fission yeast homolog Clp1p/Flp1p. The function of both
Saccharomyces cerevisiae Cdc14p and Schizosaccharomyces pombe Clp1p/Flp1p are
controlled in part by their regulated sequestration and release from the
nucleolus. In the budding yeast S. cerevisiae a set of proteins collectively
termed the FEAR network promote nucleolar and telomeric DNA segregation by
triggering the release of the conserved Cdc14 phosphatase from the nucleolus.
Here we show that FEAR homologs in S. pombe do not promote release of the Cdc14
homolog Clp1p/Flp1p from the nucleolus, and that Clp1p/Flp1p is not required for
nucleolar and telomeric DNA segregation suggesting that this aspect of Cdc14
regulation and function may not be universally conserved.
PMID- 17032734
TI - 14-3-3gamma affects dynamics and integrity of glial filaments by binding to
phosphorylated GFAP.
AB - Recent findings indicated a protective role of GFAP in ischemic brain, injured
spinal cord, and in neurodegenerative disease. We previously demonstrated that 14
3-3gamma, once thought to be neuronal specific, was up-regulated by ischemia in
astrocytes and may play a specific protective role in astrocytes. Here we report
that 14-3-3gamma associates with both soluble and filamentous GFAP in a
phosphorylation- and cell-cycle-dependent manner in primary cultured astrocytes.
The amount of association increases during G2/M phase due to more phosphorylated
GFAP. Moreover, this interaction is independent of vimentin, another type III
intermediate filament protein in astrocytes which forms glial filaments with
GFAP. A series of domain deletion mutants and substitution mutations at
phosphorylation sites (from serine to alanine) on GFAP demonstrated that serine 8
in the head domain is essential for the direct association of GFAP to 14-3
3gamma. Overexpression of 14-3-3gamma destroyed the integrity and affected the
movement of GFAP intermediate filaments. This data demonstrates that 14-3-3gamma
contributes to the regulation of dynamics of GFAP filaments, which may contribute
to the stability of the cytoskeleton and the mechanisms of central nervous system
neurodegenerative disease.
PMID- 17032735
TI - Gliotactin and Discs large form a protein complex at the tricellular junction of
polarized epithelial cells in Drosophila.
AB - The tricellular junction (TCJ) forms at the convergence of pleated septate
junctions (SJs) from three adjacent cells in polarized epithelia and is necessary
for maintaining the transepithelial barrier. In Drosophila, the transmembrane
protein Gliotactin was the first identified marker of the TCJ, but little is
known about other molecular constituents. We now show that Gliotactin associates
with Discs large at the TCJ in a Ca(2+)-dependent manner. Discs large is
essential for the formation of the TCJ and the localization of Gliotactin.
Surprisingly, Gliotactin localization at the TCJ was independent of its PDZ
binding motif and Gliotactin did not bind directly to Discs large. Therefore
Gliotactin and Discs large association is through intermediary proteins at the
TCJ. Gliotactin can associate with other septate junction proteins but this was
detected only when Gliotactin was overexpressed and spread throughout the septate
junction domain. Gliotactin overexpression and spread also resulted in a
reduction of Discs large staining but not vice versa. These results suggest that
Discs large participates in different protein interactions in the SJ and the TCJ.
Finally this work supports a model where Gliotactin and Dlg are components of a
larger protein complex that links the converging SJs with the TCJ to create the
transepithelial barrier.
PMID- 17032736
TI - BMP-2-dependent integration of adult mouse subventricular stem cells into the
neural crest of chick and quail embryos.
AB - Central nervous system (CNS) stem cells isolated from the subventricular zone
(SVZ) show a remarkable differentiation potential into neural derivatives.
Surprisingly adult SVZ cells can also be induced in vitro to differentiate into
neural crest cell fates. This fate switch is dependent on the combination of
fibroblast growth factor 2 (FGF2) and bone morphogenetic proteins (BMPs). Here we
transplanted adult SVZ stem cells from GFP mice as neurospheres into the trunk
neural tube of chick and quail embryos. Only neurospheres pre-exposed to BMP-2
and FGF2 formed close contacts with the dorsal neuroepithelium corresponding to
the neural crest area. GFP-positive cells emigrated from the neurosphere and were
identified in the roof plate, the dorsal neuroepithelium and among emigrating
neural crest cells adjacent to the neural tube. Neurospheres not treated with BMP
2 did not integrate into the neuroepithelium. Our data demonstrate that adult CNS
stem cells can be efficiently prepared in vitro for integration into the
embryonic neural crest. BMP-2 treatment conveys the necessary morphogenetic
capabilities to adult stem cells for future clinical transplantation strategies.
PMID- 17032737
TI - The nucleoporin Nup214 sequesters CRM1 at the nuclear rim and modulates NFkappaB
activation in Drosophila.
AB - CRM1-mediated protein export is an important determinant of the nuclear
accumulation of many gene regulators. Here, we show that the NFkappaB
transcription factor Dorsal is a substrate of CRM1 and requires the nucleoporin
Nup214 for its nuclear translocation upon signaling. Nup214 bound to CRM1
directly and anchored it to the nuclear envelope. In nup214 mutants CRM1
accumulated in the nucleus and NES-protein export was enhanced. Nup214 formed
complexes with Nup88 and CRM1 in vivo and Nup214 protected Nup88 from degradation
at the nuclear rim. In turn, Nup88 was sufficient for targeting the complex to
the nuclear pores. Overexpression experiments indicated that Nup214 alone
attracts a fraction of CRM1 to the nuclear envelope but does not interfere with
NES-GFP export. By contrast, overexpression of the Nup214-Nup88 complex trapped
CRM1 and Dorsal to cytoplasmic foci and inhibited protein export and immune
response activation. We hypothesize that variation in levels of the Nup214-Nup88
complex at the pore changes the amount of NPC-bound CRM1 and influences the
relative strength and duration of NFkappaB signaling responses.
PMID- 17032738
TI - RacGAP50C is sufficient to signal cleavage furrow formation during cytokinesis.
AB - Several studies indicate that spindle microtubules determine the position of the
cleavage plane at the end of cell division, but their exact role in triggering
the formation and ingression of the cleavage furrow is still unclear. Here we
show that in Drosophila depletion of either the GAP (GTPase-activating protein)
or the kinesin-like subunit of the evolutionary conserved centralspindlin complex
prevents furrowing without affecting the association of astral microtubules with
the cell cortex. Moreover, time-lapse imaging indicates that astral microtubules
serve to deliver the centralspindlin complex to the equatorial cortex just before
furrow formation. However, when the GAP-signaling component was mislocalized
around the entire cortex using a membrane-tethering motif, this caused ectopic
furrowing even in the absence of its motor partner. Thus, the GAP component of
centralspindlin is both necessary and sufficient for furrow formation and
ingression and astral microtubules provide a route for its delivery to the
cleavage site.
PMID- 17032739
TI - Inhibition of RET tyrosine kinase by SU5416.
AB - Thyroid neoplasia is frequently associated with rearranged during transfection
(RET) proto-oncogene mutations that cause hyperactivation of RET kinase activity.
Selective inhibition of RET-mediated signaling should lead to an efficacious
therapy. SU5416 is a potent inhibitor of vascular endothelial cell growth factor
receptor, c-Kit, and FLT-3 receptor tyrosine kinases presently used in clinical
trials. We found that SU5416 inhibits RET with similar potency, both in cell-free
assays and in cells, thus causing proliferation arrest in oncogenic RET
transfected cells and in papillary thyroid carcinoma (PTC) cells expressing the
RET/PTC1 oncogene, but not in RET-negative control cells. SU5416 inhibited RET
mediated signaling through the extracellular signal regulated kinase (ERK) and
JNK pathways. In addition, we show that a naturally occurring MEN2 mutation at
codon 804 confers resistance to SU5416, but not to the related compound SU4984.
We provide a possible explanation to these results by using molecular docking.
Finally, SU5416 was also assessed against an array of 52 tyrosine and
serine/threonine kinases.
PMID- 17032740
TI - Corticotropin-releasing factor and its receptors in the brain of rats with
insulin and corticosterone deficits.
AB - The expression of genes encoding corticotropin-releasing factor (CRF) and its
receptor type-1 (CRF1R) and type-2alpha (CRF2R) has been studied in the brain of
rats with streptozotocin (STZ)-induced diabetes and adrenalectomy (ADX). Diabetic
rats had a lower body weight compared to control rats. Food and water intake were
increased in diabetic rats and decreased in ADX animals. The plasma
corticosterone levels measured at the nadir of the circadian rhythm were
significantly higher in diabetic rats compared to non-diabetic animals. STZ
diabetic rats demonstrated an induction of expression of CRF mRNA in the
magnocellular part of the paraventricular hypothalamic nucleus (PVN) and in the
supraoptic nucleus (SON), whereas the CRF transcript in the parvocellular PVN was
significantly lower in rats with insulin deficiency. ADX strongly triggered the
expression of CRF mRNA in the parvocellular neurons of the PVN in both non
diabetic and diabetic rats, and it decreased magnocellular CRF mRNA in diabetic
animals. The expression of the CRF1R in the parvocellular and magnocellular PVN
and in the SON was induced by diabetes and decreased after ADX. The levels of the
CRF2R mRNA in the ventromedial hypothalamic nucleus (VMH) were significantly
lower in diabetic rats without any noticeable effects of ADX. The present results
suggest opposite effects of insulin and corticosterone deficiency on the
hypophysiotropic CRF and the CRF1R mRNA contents, whereas the expression of CRF2R
was mostly related to insulin, but not to the corticosterone status.
PMID- 17032741
TI - A temporal switch in the insulin-signalling pathway that regulates hepatic IGF
binding protein-1 gene expression.
AB - Insulin regulation of hepatic gene transcription is a vital component of glucose
homeostasis. Understanding the molecular regulationof thisprocess aids the
searchfor the defect(s) that promotesinsulin-resistant states, such
asdiabetesmellitus. We havepreviously shownthat the insulin regulationof hepatic
IGF-binding protein-1 (IGFBP1) expression requiresthe signalling proteins
phosphatidylinositol 3-kinase (PI 3-kinase) and mammalian target of rapamycin
(mTOR). In this report, we demonstrate that activation of the mTOR pathway,
without activation of its upstream regulator PI 3-kinase, reduces IGFBP1
expression. Therefore, mTOR activation is sufficient to mimic insulin regulation
of this gene. However, longer exposure (>3 h) of cells to insulin reduces the
importance of this pathway in insulin regulation of the gene, suggesting a
temporal switch in signalling mechanisms linking insulin action to the IGFBP1
gene promoter. In contrast, the activation of PI 3-kinase is required for insulin
regulation of IGFBP1 under all conditions tested. Therefore, an mTOR-independent,
PI 3-kinase-dependent pathway becomes more important in IGFBP1 regulation after
long exposure to insulin. This is a novel concept in insulin regulation of gene
expression and demonstrates the importance of temporal analysis of signalling
processes.
PMID- 17032742
TI - Characterization of bovine early growth response factor-1 and its gonadotropin
dependent regulation in ovarian follicles prior to ovulation.
AB - Early growth response factor-1 (EGR-1) is a transcription factor that is involved
in the transactivation of several genes. The objective of this study was to
characterize gonadotropin-dependent regulation of bovine EGR-1 in preovulatory
follicles prior to ovulation. Bovine EGR-1 cDNA was obtained by RT-PCR, 5'- and
3'-RACE, its open reading frame composed of 1623 bp, and its coding region
encodes a 540-amino acid protein that displays 62-93% identity to known mammalian
homologs. The regulation of EGR-1 mRNA was studied in bovine preovulatory
follicles which were isolated 0-24 h post-hCG using semiquantitative RT
PCR/Southern blot. Results revealed that the levels of EGR-1 mRNA were very low
in follicles at 0 h, markedly increased at 6 h (P < 0.05) when compared to 0 h,
and decreased between 12 and 24 h post-hCG. High levels of the EGR-1 mRNA were
also observed in corpus luteum, uterus, kidney, pituitary, and spleen, moderate
and low in other bovine tissues tested. Analyses performed on isolated
preparations of granulosa and theca cells indicated that EGR-1 mRNA was regulated
in both cell types, with a predominant expression in granulosa cells.
Immunohistochemistry on sections of preovulatory follicles isolated before and
after hCG confirmed its protein expression in granulosa cells, 24 h post-hCG.
Studies of EGR-1 regulation in primary granulosa cells cultured with forskolin
showed that levels of EGR-1 mRNA were low at 0 h, highly increased at 6 h post
forskolin (P < 0.05), and declined to steady state thereafter. Immunoblotting
confirmed forskolin-induced EGR-1 protein in cultures. Interestingly,
overexpression of EGR-1 increased the levels of mRNA for prostaglandin (PG) G/H
synthase-2 (PGHS-2), PG E synthase (PGES), PG E2 receptor (EP2), LH receptor (LH
R), but not for cytochrome P450-side chain cleavage (P450scc), and cytochrome
P450 aromatase (P450arom) in granulosa cultures. Thus, this study reports for the
first time, a gonadotropin-dependent induction of follicular EGR-1 prior to
ovulation in large monoovulatory species and its stimulating effect on the
expression of genes known to be involved in prostaglandin biosynthesis pathway,
thereby suggesting its potential involvement in the regulation of preovulatory
events in cattle.
PMID- 17032743
TI - PGC-1alpha regulates the isoform mRNA ratio of the alternatively spliced thyroid
hormone receptor alpha transcript.
AB - Transcripts derived from the thyroid hormone receptor alpha (TRalpha) gene are
alternatively spliced resulting in a functional receptor TRalpha1 and a non-T3
binding variant TRalpha2 that can exert a dominant negative effect on the
transactivation functions of other TRs. There is evidence that the ratio of
TRalpha isoform transcripts can be modulated and here, we investigate whether the
PPARgamma co-activator alpha (PGC-1alpha) has an effect on this splicing process.
PGC-1alpha was discovered not only as a transcriptional co-activator, but also
has certain motifs characteristic of splicing factors. We demonstrate that PGC
1alpha alters the ratio of endogenously expressed TRalpha isoform transcripts in
HepG2 cells, by decreasing TRalpha1 mRNA levels twofold. This change in isoform
ratio is accompanied by a decrease in 5'-deiodinase expression, whereas no
differences were found in TRbeta1 expression. Deletion of the RNA-processing
domain of PGC-1alpha abrogated the effect on the TRalpha splicing, whereas
expression of only the RNA-processing domain favored TRalpha1 expression. PGC
1alpha showed a similar effect on the splicing of a TRalpha minigene containing
only the last four exons and introns of the TRalpha gene. These data suggest that
PGC-1alpha is involved in the RNA processing of TRalpha transcripts.
PMID- 17032744
TI - Multiple microarray platforms utilized for hepatic gene expression profiling of
GH transgenic coho salmon with and without ration restriction.
AB - The objectives of this study are to examine hepatic gene expression changes
caused by GH transgenesis and enhanced growth. This is the first use of cDNA
microarrays to study the influence of GH transgenesis on liver gene expression in
a non-mammalian vertebrate, and the first such study using sexually immature
animals. Three groups of coho salmon were examined: GH transgenic on full ration
(T), GH transgenic on restricted ration (R), and control non-transgenic (C).
Specific growth rates for weight in T were approximately eightfold higher than in
C, and fourfold higher than in R. Differential gene expression in T, R, and C
samples was determined using approximately 3500 and 16,000 gene microarrays, and
R and C samples were compared on a different approximately 4000 gene microarray.
The use of multiple microarray platforms increased the overall proportion of the
hepatic transcriptome considered in these studies. Cross-platform comparisons
identified genes behaving similarly between studies. For example, genes encoding
a precerebellin-like protein and complement component C3 were downregulated in R
relative to C (R < C) in two microarray studies, and hemoglobins alpha and beta
were R > C in all three studies. Comparisons of informative gene lists within and
between studies inferred causes of altered gene expression. For example, ten
genes, including 78 kDa glucose-regulated protein, glycerol-3-phosphate
dehydrogenase, hemoglobins alpha and beta, and a C-type lectin, were likely
induced by GH transgenesis due to their presence in both T > C and R > C gene
lists. Eleven genes, including hepcidin, nuclear protein p8, precerebellin-like,
transketolase, and fatty acid-binding protein, were present in both T < C and R <
C gene lists and were, therefore, likely suppressed by GH transgenesis. A large
number of salmonid genes identified in these studies are involved in iron
homeostasis, mitochondrial function, carbohydrate metabolism, cellular
proliferation, and innate immunity. Pentose phosphate pathway genes
phosphogluconate dehydrogenase, transaldolase, and transketolase, were
dysregulated in GH transgenic samples relative to control samples. Changes in the
expression of genes involved in maintaining hemoglobin levels (heme oxygenase,
hemoglobins alpha and beta, Kruppel-like globin gene activator, hepcidin) in R
and T fish indicate a need for additional hemoglobin in the transgenic fish,
perhaps due to higher metabolic rate required for enhanced growth.
PMID- 17032745
TI - Roles of the androgen receptor cofactor p44 in the growth of prostate epithelial
cells.
AB - Various cofactors have been shown to regulate androgen receptor (AR)
transactivation, but their physiological functions in the AR pathway and prostate
tumorigenesis are undefined. Here, we found that AR cofactor (p44) translocation
from the nucleus to the cytoplasm in prostate epithelial cells (ECs) is
associated with prostate tumorigenesis. The forced nuclear localization of p44
inhibited prostate cancer cell growth by G1 cell-cycle arrest. Consistently, mice
lacking one allele of the p44 gene developed prostatic hyperplasia. Therefore,
p44 is required for proper expression of AR-target genes to maintain the
differentiation of prostate ECs, and p44 translocation from the nucleus into the
cytoplasm in prostate cancer cells or loss of one allele in mouse results in
excessive prostate EC proliferation.
PMID- 17032746
TI - The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic
mice.
AB - To understand the molecular mechanisms regulating pancreatic endocrine
development and function, pancreatic gene expression was compared between Ngn3
deficient mice and littermate controls on embryonic days 13 and 15. Microarray
analysis identified 504 genes with significant differences in expression. Fifty
two of these showed at least twofold reduction in Ngn3 knockouts compared to
controls. Many of them were previously described to be involved in endocrine
development and function. Among the genes not previously characterized were
Rhomboid veinlet-like 4, genes involved in tetrahydrobiopterin biosynthesis and
the Iroquois-type homeobox gene Irx1, the latter was selected for further
investigation. In situ hybridisation demonstrated that two Iroquois genes, Irx1
and Irx2, were expressed in pancreatic endoderm of wild-type, but not Ngn3 mutant
embryos. Furthermore, ectopic Ngn3 induced prominent Irx2 expression in chicken
endoderm. Co-labelling established that Irx1 and Irx2 mRNA is located to glucagon
, but not insulin- or somatostatin-producing cells in mice and chicken. These
data suggest that Irx1 and Irx2 serve an evolutionary conserved role in the
regulation of alpha-cell-specific gene expression.
PMID- 17032747
TI - Characterization of the Nurr1 ligand-binding domain co-activator interaction
surface.
AB - The recently solved crystal structure of the orphan nuclear receptor (NR) Nurr1
ligand-binding domain (LBD) showed that Nurr1 lacks a cavity for ligand binding
and a canonical NR co-activator-binding site. Computer modeling of the Nurr1 LBD
structure identified a hydrophobic region on the surface of the Nurr1 LBD that
was positioned on the opposite side from the classical co-activator-binding site.
Site-directed mutagenesis demonstrated that this region is critical for the
activity of the Nurr1 LBD. Most mutations introduced in this region reduced or
abolished transcriptional activity of the Nurr1 LBD, but mutation at lysine
(K577) resulted in a drastically increased activity. Moreover, the activity of
the Nurr1 LBD was shown to correlate with a propensity for proteasome-dependent
degradation revealing a close association between activity and Nurr1 protein
turnover. These data provide novel insights into the mechanisms of transcription
via the Nurr1 LBD and identify an alternative co-activator-binding surface that
is unique to the NR4A family of NRs.
PMID- 17032748
TI - Expression profiling of 11beta-hydroxysteroid dehydrogenase type-1 and
glucocorticoid-target genes in subcutaneous and omental human preadipocytes.
AB - Obesity is associated with increased morbidity and mortality from cardiovascular
disease, diabetes and cancer. Although obesity is a multi-factorial heterogeneous
condition, fat accumulation in visceral depots is most highly associated with
these risks. Pathological glucocorticoid excess (i.e. in Cushing's syndrome) is a
recognised, reversible cause of visceral fat accumulation. The aim of this study
was to identify depot-specific glucocorticoid-target genes in adipocyte precursor
cells (preadipocytes) using Affymetrix microarray technique. Confluent
preadipocytes from subcutaneous (SC) and omental (OM) adipose tissue collected
from five female patients were treated for 24 h with 100 nM cortisol (F), RNA was
pooled and hybridised to the Affymetrix U133 microarray set. We identified 72
upregulated and 30 downregulated genes by F in SC cells. In OM preadipocytes, 56
genes were increased and 19 were decreased. Among the most interesting were
transcription factors, markers of adipocyte differentiation and glucose
metabolism, cell adhesion and growth arrest protein factors involved in G-coupled
and Wnt signalling. The Affymetrix data have been confirmed by quantitative real
time PCR for ten specific genes, including HSD11B1, GR, C/EBPalpha, C/EBPbeta, IL
6, FABP4, APOD, IRS2, AGTR1 and GHR. One of the most upregulated genes in OM but
not in SC cells was HSD11B1. The GR was similarly expressed and not regulated by
glucocorticoids in SC and OM human preadipocytes. C/EBPalpha was expressed in SC
preadipocytes and upregulated by F, but was below the detection level in OM
cells. C/EBPbeta was highly expressed both in SC and in OM preadipocytes, but was
not regulated by F. Our results provide insight into the genes involved in the
regulation of adipocyte differentiation by cortisol, highlighting the depot
specifically in human adipose tissue.
PMID- 17032749
TI - Pituitary transcription factor Prop-1 stimulates porcine pituitary glycoprotein
hormone alpha subunit gene expression.
AB - Recently, we have reported that a Prophet of Pit-1 homeodomain factor, Prop-1, is
a novel transcription factor for the porcine follicle-stimulating hormone beta
subunit (FSHbeta) gene. This study subsequently aimed to examine the role of Prop
1 in the gene expression of two other porcine gonadotropin subunits, pituitary
glycoprotein hormone alpha subunit (alphaGSU), and luteinizing hormone beta
subunit (LHbeta). A series of deletion mutants of the porcine alphaGSU (up to
1059 bp) and LHbeta (up to -1277 bp) promoters were constructed in the reporter
vector, fused with the secreted alkaline phosphatase gene (pSEAP2-Basic).
Transient transfection studies using GH3 cells were carried out to estimate the
activation of the porcine alphaGSU and LHbeta promoters by Prop-1, which was
found to activate the alphaGSU promoter of -1059/+12 bp up to 11.7-fold but not
the LHbeta promoter. Electrophoretic mobility shift assay and DNase I
footprinting analysis revealed that Prop-1 binds to six positions, -1038/-1026,
942/-928, -495/-479, -338/-326, -153/-146, and -131/-124 bp, that comprise the
A/T cluster. Oligonucleotides of six Prop-1 binding sites were directly connected
to the minimum promoter of alphaGSU, fused in the pSEAP2-Basic vector, followed
by transfecting GH3 cells to determine the cis-acting activity. Finally, we
concluded that at least five Prop-1 binding sites are the cis-acting elements for
alphaGSU gene expression. The present results revealed a notable feature of the
proximal region, where three Prop-1-binding sites are close to and/or overlap the
pituitary glycoprotein hormone basal element, GATA-binding element, and
junctional regulatory element. To our knowledge, this is the first demonstration
of the role of Prop-1 in the regulation of alphaGSU gene expression. These
results, taken together with our previous finding that Prop-1 is a transcription
factor for FSHbeta gene, confirm that Prop-1 modulates the synthesis of FSH at
the transcriptional level. On the other hand, the defects of Prop-1 are known to
cause dwarfism and combined pituitary hormone deficiency accompanying
hypogonadism. Accordingly, the present observations provide a novel view to
understand the hypogonadism caused by Prop-1 defects at the molecular level
through the regulatory mechanism of alphaGSU and FSHbeta gene expressions.
PMID- 17032750
TI - Cloning and differential expression of estrogen receptor and aromatase genes in
the self-fertilizing hermaphrodite and male mangrove rivulus, Kryptolebias
marmoratus.
AB - The mechanisms underlying sex determination and differentiation in fishes are
labile in response to environmental parameters. Sex-specific phenotypes are
largely regulated by sex steroids, and the inhibition or the stimulation of
aromatase can reverse sex as well as alter secondary sexual characteristics in
fishes. Among vertebrates, the mangrove rivulus is the only known self
fertilizing hermaphrodite. Throughout most of its range, rivulus appear to exist
as clonally reproducing hermaphrodites. However, outcrossing has been documented
in Belize, where up to 25% of rivulus collected are males. The direct development
of (primary) males occurs when embryos are incubated at 18 degrees C and
hermaphrodites develop into secondary males when held at 28 degrees C. Given the
importance of sex steroids, their receptors, and aromatase in sex determination
and differentiation of fishes, we cloned, sequenced, and quantified the
expression of estrogen receptors (ERalpha, ERbeta) and ovarian (AroA) and brain
(AroB) aromatase genes. Hermaphrodites had increased ERalpha, ERbeta, AroA, and
AroB gene expression in the liver, gonad, gonad, and brain respectively, compared
to males. These data are consistent with the gene expression data reported for
other species and are reflective of the presence of ovarian tissue in the
hermaphrodites. Interestingly, we show the elevated expression of brain aromatase
in the hermaphrodite brain. The role of the dimorphic expression of brain
aromatase in the regulation of sex-specific characteristics is intriguing and
requires further research. Because of the uniqueness of its reproductive biology,
rivulus is an excellent model for elucidating the mechanisms regulating
vertebrate sex determination and sexual differentiation.
PMID- 17032751
TI - Cyclosporin A inhibits apolipoprotein AI gene expression.
AB - Cyclosporin A (CsA), a calcineurin inhibitor, has been widely used as an
immunosuppressant, and is known to induce hyperlipidemia and dyslipoproteinemia
with low levels of high-density lipoprotein (HDL). Since apolipoprotein AI (apo
AI) is a major protein component of HDL particles and reduction of apo AI results
in low levels of HDL, we hypothesized that CsA inhibits apo AI gene expression
contributing to its lipid effects. Therefore, we first measured the serum apo AI
protein levels in rats with or without CsA treatment, and found that both serum
apo AI protein and liver apo AI mRNA levels were significantly reduced in
response to CsA treatment. In stably transfected Hep G2 cells harboring an apo AI
474-CAT reporter gene, we found that intracellular calcium mobilization by A23187
a calcium ionophore stimulated apo AI gene expression and the calcineurin
inhibitors, CsA and FK605, selectively inhibited this stimulation. Therefore, we
conclude that activation of the calcineurin pathway by intracellular calcium
mobilization stimulates apo AI gene expression and calcineurin inhibition by CsA
results in reduced apo AI gene expression.
PMID- 17032752
TI - GATA factors participate in tissue-specific immune responses in Drosophila
larvae.
AB - Drosophila responds to infection by producing a broad range of antimicrobial
agents in the fat body and more restricted responses in tissues such as the gut,
trachea, and malpighian tubules. The regulation of antimicrobial genes in larval
fat depends on linked Rel/NF-kappaB and GATA binding sites. Serpent functions as
the major GATA transcription factor in the larval fat body. However, the
transcriptional regulation of other tissue-specific responses is less well
understood. Here, we present evidence that dGATAe regulates antimicrobial gene
expression in the midgut. Regulatory regions for antimicrobial genes Diptericin
and Metchnikowin require GATA sites for activation in the midgut, where Grain
(dGATAc), dGATAd, and dGATAe are expressed in overlapping domains. Ectopic
expression of dGATAe in the larval fat body, where it is normally absent, causes
dramatic up-regulation of numerous innate immunity and gut genes, as judged by
microarray analysis and in situ hybridization. Ectopic dGATAe also causes a host
of symptoms reminiscent of hyperactive Toll (Toll(10b)) mutants, but without
apparent activation of Toll signaling. Based on this evidence we propose that
dGATAe mediates a Toll-independent immune response in the midgut, providing a
window into the first and perhaps most ancient line of animal defense.
PMID- 17032753
TI - FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces
scarring, and rescues function after myocardial infarction.
AB - Mammalian cardiomyocytes have limited proliferation potential, and acutely
injured mammalian hearts do not regenerate adequately. Instead, injured
myocardium develops fibrosis and scarring. Here we show that FGF1/p38 MAP kinase
inhibitor treatment after acute myocardial injury in 8- to 10-week-old rats
increases cardiomyocyte mitosis. At 3 months after injury, 4 weeks of FGF1/p38
MAP kinase inhibitor therapy results in reduced scarring and wall thinning, with
markedly improved cardiac function. In contrast, p38 MAP kinase inhibition alone
fails to rescue heart function despite increased cardiomyocyte mitosis. FGF1
improves angiogenesis, possibly contributing to the survival of newly generated
cardiomyocytes. Our data indicate that FGF1 and p38 MAP kinase, proteins involved
in cardiomyocyte proliferation and angiogenesis during development, may be
delivered therapeutically to enhance cardiac regeneration.
PMID- 17032754
TI - A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical
multidrug resistance.
AB - Hemiasterlin is a potent antimitotic peptide that interferes with microtubule
dynamics at picomolar concentrations in cell culture. The molecule largely eludes
P glycoprotein-mediated drug efflux, and an analog is currently being evaluated
in clinical trials as cancer chemotherapy. From a nonclonal genetic screen in
Caenorhabditis elegans we isolated eight independent mutants resistant to a
synthetic hemiasterlin analog. In one recessive mutant, phb-2(ad2154), a point
mutation in prohibitin 2 (E130K) protects worms from drug-induced injury. Data
indicate that direct binding of hemiasterlin to prohibitin 2 is unlikely. In
fact, C. elegans phb-2(ad2154) was also found to be resistant to numerous other
drugs that bind tubulin and to camptothecin, yet this mutant was sensitive to
nocodazole and phalloidin. Thus, prohibitin 2 is implicated in a previously
uncharacterized pathway of multidrug resistance.
PMID- 17032755
TI - Shape and oligomerization state of the cytoplasmic domain of the phototaxis
transducer II from Natronobacterium pharaonis.
AB - Phototaxis allows archaea to adjust flagellar motion in response to light. In the
photophobic response of Natronobacterium pharaonis, light-activated sensory
rhodopsin II causes conformational changes in the transducer II protein (pHtrII),
initiating the two-component signaling system analogous to bacterial chemotaxis.
pHtrII's cytoplasmic domain (pHtrII-cyt) is homologous to the cytoplasmic domains
of eubacterial chemotaxis receptors. Chemotaxis receptors require dimerization
for activity and are in vivo-organized in large clusters. In this study we
investigated the oligomerization and aggregation states of pHtrII-cyt by using
chemical cross-linking, analytical gel-filtration chromatography, and small-angle
neutron scattering. We show that pHtrII-cyt is monomeric in dilute buffers, but
forms dimers in 4 M KCl, the physiological salt concentration for halophilic
archaea. At high ammonium sulfate concentration, the protein forms higher-order
aggregates. The monomeric protein has a rod-like shape, 202 A in length and 14.4
A in diameter; upon dimerization the length increases to 248 A and the diameter
to 18.2 A. These results suggest that under high salt concentration the shape and
oligomerization state of pHtrII-cyt are comparable to those of chemotaxis
receptors.
PMID- 17032756
TI - Proton-proton Overhauser NMR spectroscopy with polypeptide chains in large
structures.
AB - The use of 1H-1H nuclear Overhauser effects (NOE) for structural studies of
uniformly deuterated polypeptide chains in large structures is investigated by
model calculations and NMR experiments. Detailed analysis of the evolution of the
magnetization during 1H-1H NOE experiments under slow-motion conditions shows
that the maximal 1H-1H NOE transfer is independent of the overall rotational
correlation time, even in the presence of chemical exchange with the bulk water,
provided that the mixing time is adjusted for the size of the structure studied.
1H-1H NOE buildup measurements were performed for the 472-kDa complex of the 72
kDa cochaperonin GroES with a 400-kDa single-ring variant of the chaperonin GroEL
(SR1). These experiments demonstrate that multidimensional NOESY experiments with
cross-correlated relaxation-enhanced polarization transfer and transverse
relaxation-optimized spectroscopy elements can be applied to structures of
molecular masses up to several hundred kilodaltabs, which opens new possibilities
for studying functional interactions in large maromolecular assemblies in
solution.
PMID- 17032757
TI - Hot-spot mimicry of a cytokine receptor by a small molecule.
AB - Protein-protein complexes remain enticing, but extremely challenging, targets for
small-molecule drug discovery. In a rare example described earlier, a high
affinity small molecule, SP4206 (Kd approximately 70 nM), was found to block
binding of the IL-2alpha receptor (IL-2Ralpha) to IL-2 (Kd approximately 10 nM).
Recently, the structure of the IL-2/IL-2Ralpha complex was solved [Rickert, M.,
Wang, X., Boulanger, M. J., Goriatcheva, N., Garcia, K. C. (2005) Science
308:1477-1480]. Using structural and functional analysis, we compare how SP4206
mimics the 83-fold larger IL-2Ralpha in binding IL-2. The binding free energy per
contact atom (ligand efficiency) for SP4206 is about twice that of the receptor
because of a smaller, but overlapping, contact epitope that insinuates into
grooves and cavities not accessed by the receptor. Despite its independent
design, the small molecule has a similar, but more localized, charge distribution
compared with IL-2Ralpha. Mutational studies show that SP4206 targets virtually
the same critical "hot-spot" residues on IL-2 that drive binding of IL-2Ralpha.
Moreover, a mutation that enhances binding to the IL-2Ralpha near these hot spots
also enhances binding to SP4206. Although the protein and small molecule do bind
the same hot spot, they trap very different conformations of IL-2 because of its
flexible nature. Our studies suggest that precise structural mimics of receptors
are not required for high-affinity binding of small molecules, and they show that
there are multiple solutions to tight binding at shared and adaptive hot spots.
PMID- 17032758
TI - Cell-specific expression and pathway analyses reveal alterations in trauma
related human T cell and monocyte pathways.
AB - Monitoring genome-wide, cell-specific responses to human disease, although
challenging, holds great promise for the future of medicine. Patients with
injuries severe enough to develop multiple organ dysfunction syndrome have
multiple immune derangements, including T cell apoptosis and anergy combined with
depressed monocyte antigen presentation. Genome-wide expression analysis of
highly enriched circulating leukocyte subpopulations, combined with cell-specific
pathway analyses, offers an opportunity to discover leukocyte regulatory networks
in critically injured patients. Severe injury induced significant changes in T
cell (5,693 genes), monocyte (2,801 genes), and total leukocyte (3,437 genes)
transcriptomes, with only 911 of these genes common to all three cell populations
(12%). T cell-specific pathway analyses identified increased gene expression of
several inhibitory receptors (PD-1, CD152, NRP-1, and Lag3) and concomitant
decreases in stimulatory receptors (CD28, CD4, and IL-2Ralpha). Functional
analysis of T cells and monocytes confirmed reduced T cell proliferation and
increased cell surface expression of negative signaling receptors paired with
decreased monocyte costimulation ligands. Thus, genome-wide expression from
highly enriched cell populations combined with knowledge-based pathway analyses
leads to the identification of regulatory networks differentially expressed in
injured patients. Importantly, application of cell separation, genome-wide
expression, and cell-specific pathway analyses can be used to discover pathway
alterations in human disease.
PMID- 17032759
TI - Coordinated effects of distal mutations on environmentally coupled tunneling in
dihydrofolate reductase.
AB - One of the most intriguing questions in modern enzymology is whether enzyme
dynamics evolved to enhance the catalyzed chemical transformation. In this study,
dihydrofolate reductase, a small monomeric protein that catalyzes a single C-H-C
transfer, is used as a model system to address this question. Experimental and
computational studies have proposed a dynamic network that includes two residues
remote from the active site (G121 and M42). The current study compares the nature
of the H-transfer step of the WT enzyme, two single mutants, and their double
mutant. The contribution of quantum mechanical tunneling and enzyme dynamics to
the H-transfer step was examined by determining intrinsic kinetic isotope
effects, their temperature dependence, and activation parameters. Different
patterns of environmentally coupled tunneling were found for these four enzymes.
The findings indicate that the naturally evolved WT dihydrofolate reductase
requires no donor-acceptor distance fluctuations (no gating). Both single
mutations affect the rearrangement of the system before tunneling, so some gating
is required, but the overall nature of the environmentally coupled tunneling
appears similar to that of the WT enzyme. The double mutation, on the other hand,
seems to cause a major change in the nature of H transfer, leading to poor
reorganization and substantial gating. These findings support the suggestion that
these distal residues synergistically affect the H transfer at the active site of
the enzyme. This observation is in accordance with the notion that these remote
residues are part of a dynamic network that is coupled to the catalyzed
chemistry.
PMID- 17032760
TI - Quantification and rationalization of the higher affinity of sodium over
potassium to protein surfaces.
AB - For a series of different proteins, including a structural protein, enzyme,
inhibitor, protein marker, and a charge-transfer system, we have quantified the
higher affinity of Na+ over K+ to the protein surface by means of molecular
dynamics simulations and conductivity measurements. Both approaches show that
sodium binds at least twice as strongly to the protein surface than potassium
does with this effect being present in all proteins under study. Different parts
of the protein exterior are responsible to a varying degree for the higher
surface affinity of sodium, with the charged carboxylic groups of aspartate and
glutamate playing the most important role. Therefore, local ion pairing is the
key to the surface preference of sodium over potassium, which is further
demonstrated and quantified by simulations of glutamate and aspartate in the form
of isolated amino acids as well as short oligopeptides. As a matter of fact, the
effect is already present at the level of preferential pairing of the smallest
carboxylate anions, formate or acetate, with Na+ versus K+, as shown by molecular
dynamics and ab initio quantum chemical calculations. By quantifying and
rationalizing the higher preference of sodium over potassium to protein surfaces,
the present study opens a way to molecular understanding of many ion-specific
(Hofmeister) phenomena involving protein interactions in salt solutions.
PMID- 17032762
TI - Introduction: polymerization.
PMID- 17032761
TI - Early-phase transmission of Yersinia pestis by unblocked fleas as a mechanism
explaining rapidly spreading plague epizootics.
AB - Plague is a highly virulent disease believed to have killed millions during three
historic human pandemics. Worldwide, it remains a threat to humans and is a
potential agent of bioterrorism. Dissemination of Yersinia pestis, the
etiological agent of plague, by blocked fleas has been the accepted paradigm for
flea-borne transmission. However, this mechanism, which requires a lengthy
extrinsic incubation period before a short infectious window often followed by
death of the flea, cannot sufficiently explain the rapid rate of spread that
typifies plague epidemics and epizootics. Inconsistencies between the expected
rate of spread by blocked rat fleas and that observed during the Black Death has
even caused speculation that plague was not the cause of this medieval pandemic.
We used the primary vector to humans in North America, Oropsylla montana, which
rarely becomes blocked, as a model for studying alternative flea-borne
transmission mechanisms. Our data revealed that, in contrast to the classical
blocked flea model, O. montana is immediately infectious, transmits efficiently
for at least 4 d postinfection (early phase) and may remain infectious for a long
time because the fleas do not suffer block-induced mortality. These factors match
the criteria required to drive plague epizootics as defined by recently published
mathematical models. The scenario of efficient early-phase transmission by
unblocked fleas described in our study calls for a paradigm shift in concepts of
how Y. pestis is transmitted during rapidly spreading epizootics and epidemics,
including, perhaps, the Black Death.
PMID- 17032763
TI - Comprehensive genetic selection revealed essential bases in the peptidyl
transferase center.
AB - During protein synthesis, the ribosome catalyzes peptide-bond formation.
Biochemical and structural studies revealed that conserved nucleotides in the
peptidyl-transferase center (PTC) and its proximity may play a key role in
peptide-bond formation; the exact mechanism involved remains unclear. To more
precisely define the functional importance of the highly conserved residues, we
used a systematic genetic method, which we named SSER (systematic selection of
functional sequences by enforced replacement), that allowed us to identify
essential nucleotides for ribosomal function from randomized rRNA libraries in
Escherichia coli cells. These libraries were constructed by complete
randomization of the critical regions in and around the PTC. The selected
variants contained natural rRNA sequences from other organisms and organelles as
well as unnatural functional sequences; hence providing insights into the
functional roles played by these essential bases and suggesting how the universal
catalytic mechanism of peptide-bond formation could evolve in all living
organisms. Our results highlight essential bases and interactions, which are
shaping the PTC architecture and guiding the motions of the tRNA terminus from
the A to the P site, found to be crucial not only for the formation of the
peptide bond but also for nascent chain elongation.
PMID- 17032764
TI - Subelliptic boundary conditions for SpinC-Dirac operators, gluing, relative
indices, and tame Fredholm pairs.
AB - Let X be a Spin manifold with boundary, such that the Spin structure is defined
near the boundary by an almost complex structure, which is either strictly
pseudoconvex or pseudoconcave (and hence contact). Using generalized Szego
projectors, we define modified partial differential-Neumann boundary conditions,
Reo, for spinors, which lead to subelliptic Fredholm boundary value problems for
the Spin-Dirac operator, eth(eo). To study the index of these boundary value
problems we introduce a generalization of Fredholm pairs to the "tame" category.
In this context, we show that the index of the graph closure of (eth(eo), Reo)
equals the tame relative index, on the boundary, between Reo and the Calderon
projector. Let X0 and X1 be strictly pseudoconvex, Spin manifolds, as above. Let
phi : bX1 --> bX0, be a contact diffeomorphism, S0, S1 denote generalized Szego
projectors on bX0, bX1, respectively, and R0(eo), R1(eo), the subelliptic
boundary conditions they define. If X1 is the manifold X1 with its orientation
reversed, then the glued manifold X = X0 coproduct operator(phi) X1 has a
canonical Spin structure and Dirac operator, ethX(eo). Applying these results we
obtain a formula for the relative index, R-Ind(S0, phi*S1), [formula: see text].
As a special case, this formula verifies a conjecture of Atiyah and Weinstein
[(1997) RIMS Kokyuroku 1014:1-14] for the index of the quantization of a contact
transformation between cosphere bundles.
PMID- 17032765
TI - Diversin regulates heart formation and gastrulation movements in development.
AB - Canonical and noncanonical Wnt signaling regulate crucial events in the
development of vertebrates and invertebrates. In this work we show that
vertebrate Diversin, a potential orthologue of Drosophila Diego, controls fusion
of heart precursors and gastrulation movements in zebrafish embryogenesis. These
events are regulated by noncanonical Wnt signaling, which is independent of beta
catenin. We found that Diversin directly interacts with Dishevelled and that this
interaction is necessary and sufficient to mediate signals of the noncanonical
Wnt pathway to downstream effectors like Rho family GTPases and Jun N-terminal
kinase. The ankyrin repeats of Diversin are required for the interaction with
Dishevelled, for the activation of noncanonical Wnt signaling, and for the
biological responses. The mutation K446M in the DEP domain of vertebrate
Dishevelled, which mimics a classical Drosophila loss of function mutation,
prevents functional interaction with Diversin's ankyrin repeats. Diversin also
affects planar cell polarity in Drosophila, which is controlled by the
noncanonical Wnt signaling pathway. Our data thus demonstrate that Diversin and
Dishevelled function together in a mutually dependent fashion in zebrafish
gastrulation and organ formation.
PMID- 17032766
TI - Nuclearity and cooperativity effects in binuclear catalysts and cocatalysts for
olefin polymerization.
AB - A series of bimetallic organo-group 4 "constrained geometry" catalysts and
binuclear bisborane and bisborate cocatalysts have been synthesized to probe
catalyst center-catalyst center cooperativity effects on olefin enchainment in
homogenous olefin polymerization and copolymerization processes. Significant
nuclearity effects are found versus mononuclear controls, and the effect can be
correlated with metal-metal approach distances and ion pairing effects. Novel
polymer structures can be obtained by using such binuclear catalyst/cocatalyst
systems.
PMID- 17032768
TI - Kinetic resolution of racemic alpha-olefins with ansa-zirconocene polymerization
catalysts: Enantiomorphic site vs. chain end control.
AB - Copolymerization of racemic alpha-olefins with ethylene and propylene was carried
out in the presence of enantiopure C1-symmetric ansa metallocene, {1,2
(SiMe2)2(eta5-C5H-3,5-(CHMe2)2)(eta5-C5H3)}ZrCl2 to probe the effect of the
polymer chain end on enantioselection for the R- or S-alpha-olefin during the
kinetic resolution by polymerization catalysis. Copolymerizations with ethylene
revealed that the polymer chain end is an important factor in the
enantioselection of the reaction and that for homopolymerization, chain end
control generally works cooperatively with enantiomorphic site control. Results
from propylene copolymerizations suggested that chain end control arising from a
methyl group at the beta carbon along the main chain can drastically affect
selectivity, but its importance as a stereo-directing element depends on the
identity of the olefin.
PMID- 17032767
TI - Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide
gated channels.
AB - Phosphatidylinositol-3,4,5-trisphosphate (PIP3) has been proposed to modulate the
odorant sensitivity of olfactory sensory neurons by inhibiting activation of
cyclic nucleotide-gated (CNG) channels in the cilia. When applied to the
intracellular face of excised patches, PIP3 has been shown to inhibit activation
of heteromeric olfactory CNG channels, composed of CNGA2, CNGA4, and CNGB1b
subunits, and homomeric CNGA2 channels. In contrast, we discovered that channels
formed by CNGA3 subunits from cone photoreceptors were unaffected by PIP3. Using
chimeric channels and a deletion mutant, we determined that residues 61-90 within
the N terminus of CNGA2 are necessary for PIP3 regulation, and a biochemical
"pulldown" assay suggests that PIP3 directly binds this region. The N terminus of
CNGA2 contains a previously identified calcium-calmodulin (Ca2+/CaM)-binding
domain (residues 68-81) that mediates Ca2+/CaM inhibition of homomeric CNGA2
channels but is functionally silent in heteromeric channels. We discovered,
however, that this region is required for PIP3 regulation of both homomeric and
heteromeric channels. Furthermore, PIP3 occluded the action of Ca2+/CaM on both
homomeric and heteromeric channels, in part by blocking Ca2+/CaM binding. Our
results establish the importance of the CNGA2 N terminus for PIP3 inhibition of
olfactory CNG channels and suggest that PIP3 inhibits channel activation by
disrupting an autoexcitatory interaction between the N and C termini of adjacent
subunits. By dramatically suppressing channel currents, PIP3 may generate a shift
in odorant sensitivity that does not require prior channel activity.
PMID- 17032769
TI - Semicrystalline thermoplastic elastomeric polyolefins: Advances through catalyst
development and macromolecular design.
AB - We report the design, synthesis, morphology, phase behavior, and mechanical
properties of semicrystalline, polyolefin-based block copolymers. By using
living, stereoselective insertion polymerization catalysts, syndiotactic
polypropylene-block-poly(ethylene-co-propylene)-block-syndiotactic polypropylene
and isotactic polypropylene-block-regioirregular polypropylene-block-isotactic
polypropylene triblock copolymers were synthesized. The volume fraction and
composition of the blocks, as well as the overall size of the macromolecules,
were controlled by sequential synthesis of each block of the polymers. These
triblock copolymers, with semicrystalline end-blocks and mid-segments with low
glass-transition temperatures, show significant potential as thermoplastic
elastomers. They have low Young's moduli, large strains at break, and better than
90% elastic recovery at strains of 100% or less. An isotactic polypropylene-block
regioirregular polypropylene-block-isotactic polypropylene-block-regioirregular
polypropylene-block-isotactic polypropylene pentablock copolymer was synthesized
that also shows exceptional elastomeric properties. Notably, microphase
separation is not necessary in the semicrystalline isotactic polypropylenes to
achieve good mechanical performance, unlike commercial styrenic thermoplastic
elastomers.
PMID- 17032770
TI - Design of stereoselective Ziegler-Natta propene polymerization catalysts.
AB - After five decades of largely serendipitous (albeit formidable) progress,
catalyst design in Ziegler-Natta olefin polymerization, i.e., the rational
implementation of new active species to target predetermined polyolefin
architectures, has ultimately become a realistic ambition, thanks to a much
deeper fundamental understanding and major advances in the tools of computational
chemistry. In this article, we discuss, as a case history, a unique class of
stereorigid C2-symmetric bis(phenoxy-amine)Zr(IV) catalysts with controlled
kinetic behavior. A large variety of polypropylene microstructures have been
obtained with these catalysts by modulating the steric demand of one key
substituent, without altering the nature and symmetry of the ancillary ligand
framework, under the guidance of computer modeling. This unusual achievement is
relevant per se and for the perspective implications in catalyst discovery.
PMID- 17032771
TI - Study of ligand substituent effects on the rate and stereoselectivity of lactide
polymerization using aluminum salen-type initiators.
AB - A series of aluminum salen-type complexes [where salen is N,N'
bis(salicylaldimine)-1,2-ethylenediamine] bearing ligands that differ in their
steric and electronic properties have been synthesized and investigated for the
polymerization of rac-lactide. X-ray crystal structures on key precatalysts
reveal metal coordination geometries intermediate between trigonal bipyramidal
and square-based pyramidal. Both the phenoxy substituents and the backbone linker
have a significant influence over the polymerization. Electron-withdrawing groups
attached to the phenoxy donor generally gave an increased polymerization rate,
whereas large ortho substituents generally slowed down the polymerization. The
vast majority of the initiators afforded polylactide with an isotactic bias; only
one exhibited a bias toward heteroselectivity. Isoselectivity generally increases
with increased flexibility of the backbone linker, which is presumed to be better
able to accommodate any potential steric clashes between the propagating polymer
chain, the inserting monomer unit, and the substituents on the phenoxy donor.
PMID- 17032772
TI - Metallocene-catalyzed alkene polymerization and the observation of Zr-allyls.
AB - Single-site polymerization catalysts enable exquisite control over alkene
polymerization reactions to produce new materials with unique properties.
Knowledge of catalyst speciation and fundamental kinetics are essential for full
mechanistic understanding of zirconocene-catalyzed alkene polymerization.
Currently the effect of activators on fundamental polymerization steps is not
understood. Progress in understanding activator effects requires determination of
fundamental kinetics for zirconocene catalysts with noncoordinating anions such
as [B(C6F5)4]-. Kinetic NMR studies at low temperature demonstrate a very fast
propagation rate for 1-hexene polymerization catalyzed by
[(SBI)Zr(CH2SiMe3)][B(C6F5)4] [where SBI is rac-Me2Si(indenyl)2] with complete
consumption of 1-hexene before the first NMR spectrum. Surprisingly, the first
NMR spectrum reveals, aside from uninitiated catalyst, Zr-allyls as the sole
catalyst-containing species. These Zr-allyls, which exist in two diastereomeric
forms, have been characterized by physical and chemical methods. The mechanism of
Zr-allyl formation was probed with a trapping experiment, leading us to favor a
mechanism in which Zr-polymeryl undergoes beta-H transfer to metal without
dissociation of coordinated alkene followed by sigma-bond metathesis to form H2
and Zr-allyl. Zr-allyl species undergo slow reactions with alkene but react
rapidly with H2 to form hydrogenation products.
PMID- 17032773
TI - Diminishing catalyst concentration in atom transfer radical polymerization with
reducing agents.
AB - The concept of initiators for continuous activator regeneration (ICAR) in atom
transfer radical polymerization (ATRP) is introduced, whereby a constant source
of organic free radicals works to regenerate the Cu(I) activator, which is
otherwise consumed in termination reactions when used at very low concentrations.
With this technique, controlled synthesis of polystyrene and poly(methyl
methacrylate) (Mw/Mn < 1.2) can be implemented with catalyst concentrations
between 10 and 50 ppm, where its removal or recycling would be unwarranted for
many applications. Additionally, various organic reducing agents (derivatives of
hydrazine and phenol) are used to continuously regenerate the Cu(I) activator in
activators regenerated by electron transfer (ARGET) ATRP. Controlled polymer
synthesis of acrylates (Mw/Mn < 1.2) is realized with catalyst concentrations as
low as 50 ppm. The rational selection of suitable Cu complexing ligands {tris[2
(dimethylamino)ethyl]amine (Me6TREN) and tris[(2-pyridyl)methyl]amine (TPMA)} is
discussed in regards to specific side reactions in each technique (i.e., complex
dissociation, acid evolution, and reducing agent complexation). Additionally,
mechanistic studies and kinetic modeling are used to optimize each system. The
performance of the selected catalysts/reducing agents in homo and block
(co)polymerizations is evaluated.
PMID- 17032774
TI - Cyclic esters and cyclodepsipeptides derived from lactide and 2,5
morpholinediones.
AB - The reaction between Bu(n)Li in benzene and the solid polystyrene support PS
C6H4CH2NH2 leads to a lithiated species that can be represented as PS
C6H4CH2NHLi(LiBu)x, where x approximately 4, which is active in the ring-opening
of the cyclic esters L-lactide, rac-lactide, and 2,5-morpholinediones. With
approximately 10 eq of these monomeric six-membered rings and with heating,
cyclic esters (MeCHC(O)O)n and [MeCHC(O)OCHRC(NH)O]n are reversibly released to
the solution. These have been characterized by electrospray ionization MS, and
some small rings have been separated by gel-permeation chromatography. Addition
of NaBPh4 to a heated benzene solution containing these rings preferentially
removes the 18-membered rings from solution. For lactide this is shown to form
the basis for chemical amplification from a dynamic combinatorial library and
lactide can be converted to (MeCHC(O)O)6 in >80% yield. Metallated supports
derived from Me2Mg and Et2Zn are less reactive but do show some ability for
lactide ring-enlarging. The 18-membered ring (R,R,R,S,S,S)- and meso
(R,S,R,S,R,S)-(MeCHC(O)O)6 and the 24-membered ring (MeCHC(O)OCHPr(i)C(NH)O)4
have been characterized by single-crystal x-ray diffraction studies, together
with the complex Na[eta3-S,S,S,S,S,S-(MeCHC(O)O)6]2BPh4.
PMID- 17032775
TI - Ansa-metallocene polymerization catalysts derived from [2+2]cycloaddition
reactions of bis(1-methylethenyl-cyclopentadienyl)zirconium systems.
AB - Bis(1-methylethenyl-cyclopentadienyl)zirconium dichloride (7a) was prepared by a
fulvene route. Photolysis at 0 degrees C with Pyrex-filtered UV light resulted in
a rapid and complete intramolecular [2+2]cycloaddition reaction to yield the
corresponding cyclobutylene-bridged ansa-zirconocene dichloride isomer (8a). This
is one of the rare examples of an organic functional group chemistry that leads
to carbon-carbon coupling at the framework of an intact sensitive group 4 bent
metallocene complex. More sterically hindered open metallocenes that bear bulky
isopropyl or tert-butyl substituents at their Cp rings in addition to the active
1-methylethenyl functional group undergo the photochemical ansa-metallocene ring
closure reaction equally facile. The metallocene systems used and obtained in
this study have served as transition metal components for the generation of
active metallocene propene polymerization catalysts.
PMID- 17032776
TI - Surface science of single-site heterogeneous olefin polymerization catalysts.
AB - This article reviews the surface science of the heterogeneous olefin
polymerization catalysts. The specific focus is on how to prepare and
characterize stereochemically specific heterogeneous model catalysts for the
Ziegler-Natta polymerization. Under clean, ultra-high vacuum conditions, low
energy electron irradiation during the chemical vapor deposition of model Ziegler
Natta catalysts can be used to create a "single-site" catalyst film with a
surface structure that produces only isotactic polypropylene. The polymerization
activities of the ultra-high vacuum-prepared model heterogeneous catalysts
compare well with those of conventional Ziegler-Natta catalysts. X-ray
photoelectron spectroscopic analyses identify the oxidation states of the Ti ions
at the active sites. Temperature-programmed desorption distinguishes the binding
strength of a probe molecule to the active sites that produce polypropylenes
having different tacticities. These findings demonstrate that a surface science
approach to the preparation and characterization of model heterogeneous catalysts
can improve the catalyst design and provide fundamental understanding of the
single-site olefin polymerization process.
PMID- 17032777
TI - "Dormant" secondary metal-alkyl complexes are not omnipresent.
AB - This theoretical study was inspired by the perpetual debate over the so-called
"dormancy" of the active sites in propylene polymerization, i.e., a drop in their
activity after a regioerror (2,1-insertion), which was reported to occur in many
(although not all) catalytic systems. To explore the range of possible
situations, we have selected two homogeneous systems of fundamentally different
structure: an octahedral system of C2 symmetry with a tetradentate -O-N-N-O-
ligand and a bridged indenyl catalyst. This choice was not accidental; it is in
these two systems where the experimentalists cannot reach a consensus about
dormancy. Our density-functional theory calculations explain why in certain
catalytic systems both primary and secondary alkyl complexes can be equally
reactive toward propylene polymerization, despite the intuitive concept of
dormancy. To understand such a behavior, it was imperative to build an extensive
model, including the counteranion and solvent effects. The discussion is also
supplemented by our latest calculations on the classical second-generation
Ziegler-Natta system.
PMID- 17032779
TI - Running over rough terrain reveals limb control for intrinsic stability.
AB - Legged animals routinely negotiate rough, unpredictable terrain with agility and
stability that outmatches any human-built machine. Yet, we know surprisingly
little about how animals accomplish this. Current knowledge is largely limited to
studies of steady movement. These studies have revealed fundamental mechanisms
used by terrestrial animals for steady locomotion. However, it is unclear whether
these models provide an appropriate framework for the neuromuscular and
mechanical strategies used to achieve dynamic stability over rough terrain.
Perturbation experiments shed light on this issue, revealing the interplay
between mechanics and neuromuscular control. We measured limb mechanics of
helmeted guinea fowl (Numida meleagris) running over an unexpected drop in
terrain, comparing their response to predictions of the mass-spring running
model. Adjustment of limb contact angle explains 80% of the variation in stance
phase limb loading following the perturbation. Surprisingly, although limb
stiffness varies dramatically, it does not influence the response. This result
agrees with a mass-spring model, although it differs from previous findings on
humans running over surfaces of varying compliance. However, guinea fowl
sometimes deviate from mass-spring dynamics through posture-dependent work
performance of the limb, leading to substantial energy absorption following the
perturbation. This posture-dependent actuation allows the animal to absorb energy
and maintain desired velocity on a sudden substrate drop. Thus, posture-dependent
work performance of the limb provides inherent velocity control over rough
terrain. These findings highlight how simple mechanical models extend to unsteady
conditions, providing fundamental insights into neuromuscular control of movement
and the design of dynamically stable legged robots and prosthetic devices.
PMID- 17032780
TI - Identification of the bovine cholesterol efflux regulatory protein ABCA1 and its
expression in various tissues.
AB - The ATP-binding cassette transporter A1 (ABCA1) is known to play a significant
role in cellular export of phospholipids and cholesterol in humans. The ABCA1
transporter might also play a crucial role in cellular cholesterol homeostasis in
the cow or in the transfer of cholesterol into the milk, but its presence and
tissue distribution in the bovine is unknown. Therefore, we studied the
expression and distribution of the bovine ABCA1 transporter using quantitative
PCR and sequenced the entire ABCA1 coding region. In addition, the proximal
promoter was identified and screened for regulatory elements. Concordant with
data from other mammalian species, bovine ABCA1 mRNA was expressed and detected
in all tissues tested. The highest expression levels were detected in lung,
esophagus, uterus, spleen, and muscle. Sequence analysis revealed that the open
reading frame of this gene consists of 6,786 bases and encodes for a protein of
2,261 AA with a predicted molecular weight of 254 kDa. The deduced bovine ABCA1
protein shows the highest AA sequence homology with human (94%), mouse (93%), rat
(92%), and chicken (85%). Analysis of the putative ABCA1 promoter region revealed
potential transcription factor binding sites associated with ABCA1 transcription
and lipid metabolism. This work could open new avenues for elucidating a
potential role of ABCA1 in sterol homeostasis in the bovine organism.
PMID- 17032778
TI - Neural correlates of epigenesis.
AB - The effect of life stress on depression is moderated by a repeat length variation
in the transcriptional control region of the serotonin transporter gene, which
renders carriers of the short variant vulnerable for depression. We investigated
the underlying neural mechanisms of these epigenetic processes in individuals
with no history of psychopathology by using multimodal magnetic resonance-based
imaging (functional, perfusion, and structural), genotyping, and self-reported
life stress and rumination. Based on functional MRI and perfusion data, we found
support for a model by which life stress interacts with the effect of serotonin
transporter genotype on amygdala and hippocampal resting activation, two regions
involved in depression and stress. Life stress also differentially affected, as a
function of serotonin transporter genotype, functional connectivity of the
amygdala and hippocampus with a wide network of other regions, as well as gray
matter structural features, and affected individuals' level of rumination. These
interactions may constitute a neural mechanism for epigenetic vulnerability
toward, or protection against, depression.
PMID- 17032781
TI - Identification of quantitative trait loci affecting corpora lutea and number of
teats in a Meishan x Duroc F2 resource population.
AB - Understanding of the genetic control of female reproductive performance in pigs
would offer the opportunity to utilize natural variation and improve selective
breeding programs through marker-assisted selection. The Chinese Meishan is one
of the most prolific pig breeds known, farrowing 3 to 5 more viable piglets per
litter than Western breeds. This difference in prolificacy is attributed to the
Meishan's superior prenatal survival. Our study utilized a 3-generation resource
population, in which the founder grandparental animals were purebred Meishan and
Duroc pigs, in a genome scan for QTL. Grandparent, F1, and F2 animals were
genotyped for 180 microsatellite markers. Reproductive traits, including number
of corpora lutea (number of animals = 234), number of fetuses per animal (n =
226), number of teats (n = 801), and total number born (n = 288), were recorded
for F2 females. Genome-wide significance level thresholds of 1, 5, and 10% were
calculated using a permutation approach. We identified 9 QTL for 3 traits at a
10% genome-wise significance level. Parametric interval mapping analysis
indicated evidence of a 1% genome-wise significant QTL for corpora lutea on SSC
3. Nonparametric interval mapping for number of teats found 4 significant QTL on
chromosomes SSC3 (P < 0.01), SSC7 (P < 0.01), SSC8 (P < 0.01), and SSC12 (P <
0.05). Partial imprinting of a QTL affecting teat number (P < 0.10) was detected
on SSC8. Using the likelihood-ratio test for a categorical trait, 2 QTL for pin
nipples were detected on SSC2 and SSC16 (P < 0.01). Fine mapping of the QTL
regions will be required for their application to introgression programs and gene
cloning.
PMID- 17032782
TI - Identification of a single nucleotide polymorphism of the insulin-like growth
factor binding protein 2 gene and its association with growth and body
composition traits in the chicken.
AB - Insulin-like growth factor binding protein 2 regulates a broad spectrum of
biological activities involved in growth, development, and differentiation. The
current study was designed to investigate the associations of IGFBP2 gene
polymorphisms with chicken growth and body composition traits. The Northeast
Agricultural University Resource Population (NEAURP) was established by crossing
broiler sires, derived from lines at Northeast Agricultural University, that were
divergently selected for abdominal fat, with Baier layer dams, a Chinese local
breed. The F1 birds were inter-crossed to produce an F2 population. Body weight
and body composition traits were measured in the NEAURP. The PCR primers for the
intron 2 region of IGFBP2 were designed based on chicken genomic sequence.
Nucleotide polymorphisms between parental lines were detected by DNA sequencing.
A C/T SNP in intron 2 was detected, and PCR-RFLP methods were then developed to
genotype the F2 individuals. The results showed that the IGFBP2 SNP was
associated with multiple traits, including BW, metatarsus length, shank length,
femur length, shank weight, femur weight, metatarsus claw weight, and abdominal
fat weight in the 1,028 NEAURP F2 individuals. This research suggests that IGFBP2
or a tightly linked gene has broad effects on growth and development in the
chicken.
PMID- 17032783
TI - Adipocyte fatty-acid binding protein is closely associated to the porcine FAT1
locus on chromosome 4.
AB - We identified 22 polymorphisms in the adipocyte fatty-acid binding protein
(FABP4) gene, a strong positional candidate gene for the FAT1 locus in porcine
chromosome 4. The most informative polymorphism, an insertion/deletion in intron
1, together with a single nucleotide polymorphism in intron 3, was genotyped in a
cross between Iberian and Landrace pigs. After performing QTL, single marker, and
haplotype analyses, we showed that there were at least 2 quantitative trait genes
in the FAT1 region and that the FABP4 polymorphism was tightly associated to
fatness. A comparison of allelic frequencies in a panel of pig breeds suggested
that the Del2634C polymorphism was under indirect selection. We also showed that
FABP4 is tightly associated to fatness but not growth. Furthermore, a haplotype
analysis suggests that there is genetic heterogeneity at the FAT1 locus within
the Landrace breed.
PMID- 17032784
TI - Analysis of longevity and exterior traits on Large White sows in Switzerland.
AB - Records of length of productive life, from first farrowing to culling, of 16,464
Large White purebred sows from SUISAG were studied using survival analysis. The
major aims of the study were to model the risk of culling within parity and to
assess the influence of exterior traits, such as the number of teats or feet and
leg scores, on culling. Culling was concentrated at the first day after each
farrowing or at the first day after weaning. Weaning itself was mostly between 21
and 49 d after farrowing, with an average weaning age of 35 d. Because of the
definition of culling date used, there was practically no risk of culling from
these periods. The culling rates at different periods suggested a modeling of the
baseline hazard function within parity instead of over the entire productive life
of the animals. A piecewise Weibull function and a simple graphical method to
validate its adequacy were proposed for sow longevity analysis. The risk of
culling increased with older parities (P < 0.001) and with decreasing litter size
at weaning (P < 0.001). The exterior traits analyzed (number of teats, and feet
and leg scores, on a scale from 1 to 7) had a moderate effect on the risk of
culling compared with other factors but were still influential on survival,
productive life expectancy, and annual replacement rate. Sows with less than 13
good teats had 1.35 times greater risk of being culled than sows with more good
teats (P < 0.05). Sows with an X-O rear leg score of 2 had 1.4 times greater risk
of being culled than sows with an intermediate score of 4 (P < 0.05). Sows at the
optimum score of 4 for the size of inner claws of the rear leg had 0.83 times
less risk of being culled (P < 0.01) than sows with scores of 2 and 3.
Furthermore, when a phenotypic index for feet and legs was used to group these
variables, the effect was highly significant (P < 0.001). Therefore, a means to
improve longevity is through phenotypic selection of replacement gilts based on
exterior traits: gilts with 13 or less good teats or with extreme feet and leg
scores should be culled. From a genetic point of view, sows with the best value
in the current index for exterior traits had a lower risk of culling (P < 0.01),
and therefore, it is possible to obtain a response for sow longevity via indirect
selection for exterior traits. From 1999 to 2003, the trend has been to eliminate
extreme animals on exterior traits. This may partly explain the improvement of
sow length of productive life longevity from 560 d in 2000 to nearly 710 d in
2003 observed in the data set.
PMID- 17032785
TI - Genetic effects on preweaning weight gain of Nelore-Hereford calves according to
different models and estimation methods.
AB - Additive and nonadditive genetic effects on preweaning weight gain (PWG) of a
commercial crossbred population were estimated using different genetic models and
estimation methods. The data set consisted of 103,445 records on purebred and
crossbred Nelore-Hereford calves raised under pasture conditions on farms located
in south, southeast, and middle west Brazilian regions. In addition to breed
additive and dominance effects, the models including different epistasis
covariables were tested. Models considering joint additive and environment
(latitude) by genetic effects interactions were also applied. In a first step,
analyses were carried out under animal models. In a second step, preadjusted
records were analyzed using ordinary least squares (OLS) and ridge regression
(RR). The results reinforced evidence that breed additive and dominance effects
are not sufficient to explain the observed variability in preweaning traits of
Bos taurus x Bos indicus calves, and that genotype x environment interaction
plays an important role in the evaluation of crossbred calves. Data were ill
conditioned to estimate the effects of genotype x environment interactions.
Models including these effects presented multicolinearity problems. In this case,
RR seemed to be a powerful tool for obtaining more plausible and stable
estimates. Estimated prediction error variances and variance inflation factors
were drastically reduced, and many effects that were not significant under
ordinary least squares became significant under RR. Predictions of PWG based on
RR estimates were more acceptable from a biological perspective. In temperate and
subtropical regions, calves with intermediate genetic compositions (close to 1/2
Nelore) exhibited greater predicted PWG. In the tropics, predicted PWG increased
linearly as genotype got closer to Nelore.
PMID- 17032786
TI - A structural equation model for describing relationships between somatic cell
score and milk yield in dairy goats.
AB - The relationship between milk yield and somatic cell score (log-transformed
somatic cell count) in dairy goats may involve complex pathways with recursive or
simultaneous effects. Structural equation models were fitted to longitudinal data
on milk yield and on somatic cell scores. Data consisted of 4 repeated records of
milk production and of somatic cell score from left and right halves of the udder
in each of 47 dairy goats; infection status of each of the halves at each test
day was also available. Results strongly suggest the existence of a within-half,
first-order autoregressive process and of simultaneity of effects between somatic
cell scores from the left and right halves of the udder. This indicates that the
immune response to an infection is not restricted to the half of the udder in
which the infection takes place and that it tends to propagate over time. The
existence of a negative effect of somatic cell score on milk yield was also
supported by the results; however, evidence in favor of an effect in the opposite
direction, a dilution effect, was not strong.
PMID- 17032787
TI - Enhanced skeletal growth of sheep heterozygous for an inactivated fibroblast
growth factor receptor 3.
AB - Normal fibroblast growth factor receptor 3 (FGFR3) acts as a negative bone growth
regulator by restricting chondrocyte proliferation and endochondral bone
elongation. In sheep, a heritable mutation that inactivates FGFR3 produces
skeletal overgrowth when homozygous, this condition is commonly referred to as
spider lamb syndrome (SLS). We hypothesized that sheep heterozygous for the
inactivated FGFR3 mutation (FGFR3(SLS/+)) would exhibit enhanced long bone growth
and greater frame size; additionally, the isolated effects of increased bone
growth would translate into greater BW and larger LM area relative to normal
lambs at harvest. The current study investigated bone length and LM area of
FGFR3(SLS/+) sheep at maturity and during growth. At maturity, FGFR3(SLS/+) ewes
exhibited a larger frame size and longer bones than normal FGFR3(+/+) ewes (P <
0.05). Similarly, FGFR3(SLS/+) lambs had greater frame sizes than normal
FGFR3(+/+) lambs, as indicated by increased metacarpal III length and height at
withers (P < 0.05). The FGFR3(SLS/+) lambs took longer than the normal FGFR3(+/+)
lambs to reach the 60-kg common BW harvest end point (P < 0.05). The FGFR3(SLS/+)
lambs showed no difference in BW, ADG, or LM area at any age compared with normal
FGFR3(+/+) lambs (P > 0.2). A similar LM area produced in the context of a
greater frame size and skeletal length produces a greater muscle volume, thereby
potentially increasing meat yield. The results of this study suggest that
FGFR3(SLS/+) animals exhibit a relaxation of the normal inhibition of chondrocyte
proliferation, resulting in an increase in the overall frame size. The sheep
industry could utilize the naturally occurring genetic mutation in FGFR3 to
potentially increase meat yields with enhanced skeletal growth as an alternative
to exogenous growth promotants.
PMID- 17032788
TI - Melengestrol acetate alters muscle cell proliferation in heifers and steers.
AB - In vitro experiments were performed to investigate the effects of melengestrol
acetate (MGA) or progesterone (P4) on bovine muscle satellite cells and C2C12
myoblasts. Addition of MGA at physiological and supraphysiological concentrations
resulted in a dose-dependent decrease (P < 0.05) in DNA synthesis as measured by
[3H]-thymidine incorporation (TI). Similarly, P4 addition (0.01 nM) reduced (P <
0.05) TI. Addition of MGA (10 nM) increased (P < 0.05) IGF-I mRNA abundance but
did not affect myogenin mRNA. Progesterone addition (10 nM) increased myogenin
mRNA abundance (P < 0.05). In C2C12 cultures, P4 addition resulted in a dose
dependent decrease in TI. The antiprogestin RU486, in combination with MGA or P4,
also resulted in reduced (P < 0.05) TI. Treatment with RU486 alone had a negative
effect (P < 0.05) on TI that was similar to the progestins. Treatment of C2C12
myoblasts with MGA (100 nM) resulted in an increase (P < 0.05) in myogenin mRNA.
These studies suggest that progestins may reduce satellite cell proliferation,
ultimately affecting carcass composition.
PMID- 17032789
TI - Growth- and breed-related changes of muscle bundle structure in cattle.
AB - The objective of this study was to investigate the changes in muscle fiber
bundles of cattle of different breeds during growth. Different numbers of muscle
fibers are surrounded by connective tissue to form bundles macroscopically
visible as meat fibers or meat grain, a common meat quality trait. To determine
the influence of breed and age on morphological characteristics of muscle fiber
bundles, 4 cattle breeds with different growth impetus and muscularity were
reared and slaughtered under experimental conditions. German Angus, a typical
beef cattle; Galloway, a smaller beef type; Holstein Friesian, a dairy type; and
double-muscled Belgian Blue, an extreme type for muscle growth, were used.
Between 5 and 15 bulls of each breed were slaughtered at 2, 4, 6, 12, or 24 mo of
age, and slices of semitendinosus muscle were removed. Muscle structure
characteristics were determined by computerized image analysis. During growth,
the muscle cross-sectional area enlarged (P < 0.001) about 5-fold in double
muscled Belgian Blue bulls and about 4-fold in the other breeds. This was a
result of the enlargement (P < 0.001) of primary bundles and muscle fibers. The
bundle size was similar (P > or = 0.15) in bulls of German Angus and Galloway in
all age groups and was doubled (P < 0.001) in double-muscled Belgian Blue animals
from 4 mo of age on. The Holstein Friesian bulls had the smallest (P < 0.001)
muscle fiber bundles at 24 mo of age. The number of muscle fibers per bundle and
the number of bundles per muscle remained nearly constant (P > 0.05) during
growth. This supports the existing view that the structure of the muscle is
already fixed in prenatal life. The double-muscled Belgian Blue bulls showed a
more than 2.5-fold greater (P < 0.001) number of muscle fibers per primary bundle
compared with the other breeds investigated. The larger muscle fiber bundles led
to a smaller amount of connective tissue per muscle area in double-muscled
cattle. The coarser grain of meat in double-muscled Belgian Blue bulls and in
older animals was not related to greater shear force values.
PMID- 17032790
TI - Effects of level of feed intake on pancreatic exocrine secretions during the
early postweaning period in piglets.
AB - The objective of this study was to determine the influence of the level of feed
intake and a 2-d feed restriction period on the postweaning adaptation of
pancreatic exocrine secretions. At 33 d of age, 18 piglets fitted with 2
permanent catheters (for pancreatic juice collection and reintroduction) were
weaned and allocated to 1 of the following 2 dietary treatments for 5 d:
restricted feed allocation (restricted) or gradually increasing feed allocation
(control). Pancreatic juice was collected daily during both basal and prandial
periods. The basal period was defined as the period from 1400 to 1700 h (i.e., 5
to 8 h after the morning meal), whereas the prandial period was defined as the
period from 30 min before to 60 min after the morning meal (given at 0900).
Digestive enzyme activities and antibacterial activity were determined.
Pancreatic protein secretion was 44% less (P < 0.05) in restricted piglets than
in control piglets during the basal period. Trypsin secretion was affected by
feed-restriction of piglets. The meal did not affect protein and trypsin
secretions in restricted piglets, whereas at d 3 postweaning, protein and trypsin
secretions and trypsin specific activity in control piglets were 9-, 105-, and 25
fold greater (P < 0.001) during the first 30 min after the meal than before the
meal. Lipase and amylase secretions were not affected by variations in feed
intake. The secretion of antibacterial activity in restricted piglets was greater
(P < 0.05) than that of control piglets only at d 5. The extended feed
restriction period increased the basal secretion of antibacterial activity (P =
0.09) and postprandial secretion of amylase (P = 0.05). In conclusion, a low
level of feed intake during the early postweaning period decreased pancreatic
protein and trypsin secretions, whereas a 2-d feed restriction period enhanced
secretions of amylase and antibacterial activity. In addition, our results
indicate that during periods of dietary adaptation, such as at weaning,
measurements of enzyme activities in the tissue do not accurately reflect the
enzyme secretion.
PMID- 17032792
TI - Gene expression of myostatin during development and regeneration of skeletal
muscle in Japanese Black Cattle.
AB - Myostatin is a specific negative regulator of skeletal muscle growth and is
regarded as one of the most important factors for myogenesis. The aim of the
current study was to analyze the developmental change in the gene expression of
myostatin and an adipogenic transcription factor (peroxisome proliferator
activated receptor lambda2) in the semitendinosus muscle of Japanese Black Cattle
throughout the whole life cycle. An additional aim was to compare the temporal
expression patterns of myostatin and relevant myogenic regulatory factors (MRF)
mRNA during muscle regeneration after frostbite injury at 16 mo of age. The
developmental pattern of myostatin gene expression exhibited 2 peaks: the
greatest expression occurred in utero (P <0.05) and the second greatest occurred
at 16 mo of age (P <0.05). The greatest level of peroxisome proliferator
activated receptor lambda2 expression was observed at 16 mo of age (P <0.05),
which paralleled myostatin expression. During frostbite-induced muscle
regeneration, gene expression for myostatin and 4 MRF; i.e., Myf5, MyoD, myogenin
and MRF4, showed contrasting responses. Myostatin mRNA dramatically declined by
68.1 and 82.6% at 3 and 5 d after injury (P <0.05), respectively, which
paralleled its protein expression, and was restored at 10 d. In contrast, the
expressions of all 4 MRF mRNA were low initially but increased by 5 d after
injury (P <0.05) and then remained constant or decreased slightly. These results
suggest that myostatin may play a role in muscle marbling in the fattening period
by decreasing myogenesis and increasing adipogenesis, and that the interaction
between myostatin and MRF genes may take place at an early stage of skeletal
muscle regeneration.
PMID- 17032791
TI - Effect of anabolic agents on calpastatin promoters in porcine skeletal muscle and
their responsiveness to cyclic adenosine monophosphate- and calcium-related
stimuli.
AB - The calpain proteinases and their specific inhibitor calpastatin have been
proposed to influence both the rates of myofibrillar protein turnover in vivo and
meat tenderization postmortem. Elevated calpastatin concentrations in particular
are associated with certain forms of hypertrophic growth and meat toughness. In
the 5'region of the porcine calpastatin gene, there are 3 calpastatin promoters
upstream of exons 1xa, 1xb, and 1u, respectively, each of which contain
transcription factor-binding motifs, suggesting sensitivity to a variety of
growth-promoting stimuli. This study examined the effect of the beta-adrenergic
agonist clenbuterol and porcine ST (pST) treatment on calpastatin promoter usage
in porcine LM in vivo using real-time PCR and also the responsiveness of
transfected calpastatin promoter sequences to cyclic adenosine monophosphate
(cAMP) and calcium (Ca2+)-related stimuli in reporter gene systems in cell
studies. The effect of clenbuterol and pST on potential signaling pathways in
vivo was also assessed by monitoring protein phosphatase 2B (calcineurin),
NFATc3, calpain 3, IkappaB alpha, and NFkappaB by quantitative immunoblotting.
Total calpastatin mRNA was increased by 52% (P < 0.05) after treatment with
clenbuterol for 1 d and reduced by 35% (P < 0.01) after pST treatment for 7 d.
Whereas clenbuterol had no significant differential effects on individual mRNA
transcripts (types 1 to 3) derived from the 3 upstream promoters, pST
significantly reduced all of these by 51, 39, and 40% (P < 0.001, 0.05, and
0.05), respectively. Promoter activity was increased in rat L6G8 cells
transfected with a construct derived from exon 1u after treatment with dibutyryl
cAMP (68%, P < 0.05) or forskolin (43%, P < 0.05), whereas 1xa activity was
reduced by both of these agents (47 and 33%, respectively, P < 0.05). Treatment
of cells with the calcium ionophore calcimycin reduced the activity of the 1u
promoter by 40% (P < 0.01), with no effect on the other promoter constructs.
Cyclosporin A had no effect on any promoter construct. The only signaling pathway
component to be significantly altered by the in vivo treatments was calcineurin,
which was decreased by 24% (P < 0.05) in clenbuterol-treated animals. In
conclusion, 2 types of growth promoter in pigs had contrasting effects on
calpastatin expression in LM. Transfected calpastatin promoters were
differentially sensitive to cAMP- and Ca2+-related stimuli, in agreement with the
proposed mode of action of the 2 growth promoters.
PMID- 17032793
TI - Immunization of pigs against chicken gonadotropin-releasing hormone-II and
lamprey gonadotropin-releasing hormone-III: effects on gonadotropin secretion and
testicular function.
AB - The objective of this experiment was to evaluate the effects of active
immunization against 2 GnRH isoforms on gonadotropin secretion and testicular
function in pigs. Synthetic chicken (c) GnRH-II and lamprey (l) GnRH-III
peptides, with the common pGlu-His-Trp-Ser sequence at the N-terminal omitted,
were conjugated to BSA. Forty-eight male piglets were randomly assigned to 1 of 4
treatments. Pigs on treatment 1 were actively immunized against cGnRH-II, whereas
pigs on treatment 2 were actively immunized against lGnRH-III. Control pigs on
treatment 3 were actively immunized against the carrier protein (BSA), and pigs
on treatment 4 were castrated and actively immunized against BSA. The BSA
conjugate was emulsified in Freund's Incomplete Adjuvant and
diethylaminoethyldextran. Primary immunization was given at 13 wk of age (WOA)
with booster immunizations given at 16 and 19 WOA. Body weight and plasma samples
were collected weekly beginning at 11 WOA. Treatments did not affect BW during
the experimental period. Antibody titers were increased in animals immunized
against cGnRH-II and lGnRH-III (P < 0.001). Cross-reactivity of the antibodies to
mammalian GnRH or between cGnRH-II and lGnRH-III was minimal. Concentrations of
testosterone were maximal in control boars (treatment 3) and minimal in control
barrows (treatment 4) and immunized pigs (treatment x week; P < 0.01). Immunized
animals had concentrations of LH (P < 0.001) and FSH (treatment x week; P < 0.03)
that were less than control barrows and similar to control boars. At the end of
the experiment, intact (noncastrated) pigs were exsanguinated. Testes were
removed immediately; Leydig cells were isolated and treated with 0, 1, or 10
ng/mL of LH. There was an LH x GnRH treatment effect on testosterone
concentrations (P < 0.03), indicating that Leydig cells were sensitive to the
immunization protocol and doses of LH. Taken together, these data suggest that
immunization against GnRH isoforms decreased gonadotropin secretion compared with
control barrows. Additionally, immunization against cGnRH-II and lGnRH-III
reduced the ability of Leydig cells to respond to LH challenges.
PMID- 17032795
TI - Muscle growth and plasma concentrations of amino acids, insulin-like growth
factor-I, and insulin in growing pigs fed reduced-protein diets.
AB - Twenty barrows were used to determine if partial replacement of protein-bound AA
with crystalline AA (CAA) reduces AA use for muscle tissue and whole-body growth.
Barrows (44.2 +/- 1.3 kg of BW) were assigned to 4 diets in a randomized complete
block design. Diets consisted of 16.1% CP with no CAA, and 12.8, 10.1, and 7.8%
CP containing CAA. As the CP concentration decreased, CAA were gradually
increased to meet requirements on a true ileal digestibility basis. Barrows were
weighed on d 0 and 13. Blood samples were collected before the morning feeding on
d 0, 6, and 12 (prefeeding), and 2 h after the morning feeding on d 13
(postfeeding). Pigs were euthanized on d 13, and liver and right LM were removed
and weighed. The reduction in the dietary CP concentration linearly decreased (P
< 0.01) ADG, G:F, LM weight, and the CP content of LM. Reducing the CP
concentration decreased pre- and postfeeding plasma concentrations of IGF-I
(linear, P < 0.01) and insulin (linear, P < 0.10). The reduction in the dietary
CP concentration increased prefeeding plasma concentrations of Ala, Gln, Gly, and
total AA but decreased Arg, Asn, His, Ile, Phe, Trp, and Tyr (linear, P < 0.05).
Plasma concentration of total indispensable AA decreased initially and increased
thereafter as the dietary CP concentration decreased from 16.1 to 7.8%
(quadratic, P < 0.01). The reduction in the dietary CP concentration increased
postfeeding plasma concentrations of Ala, Lys, Met (linear, P < 0.01), and Gly
(linear, P = 0.073) and decreased Asn, Ser, Tyr, Arg, His, and Leu (linear, P <
0.05). Plasma concentrations of Ile, Phe, Thr, Trp, and Val decreased initially
and increased thereafter as the dietary CP concentration decreased from 16.1 to
7.8% (quadratic, P < 0.05). In muscle tissue, concentrations of free Ala, Asp,
Glu, Gln, Gly, and Lys increased (linear, P < 0.05) as the dietary CP
concentration decreased. Concentrations of free His, Ile, Phe, Thr, Trp, and Val
in muscle tissue decreased initially and increased thereafter as the dietary CP
concentration decreased from 16.1 to 7.8% (quadratic, P < 0.05). In summary, the
reduction in the dietary protein-bound AA decreased whole-body and LM growth,
altered the free AA pool profile in muscle tissue, and decreased plasma insulin
and IGF-I. As the replacement of protein-bound AA with CAA increased, 1) free Ala
and Gln in muscle tissue increased, indicating an increase of muscle tissue
protein breakdown; and 2) utilization of indispensable AA in muscle tissue
decreased.
PMID- 17032794
TI - Synchronization of estrus and artificial insemination in replacement beef heifers
using gonadotropin-releasing hormone, prostaglandin F2alpha, and progesterone.
AB - We evaluated whether a fixed-time AI (TAI) protocol could yield pregnancy rates
similar to a protocol requiring detection of estrus, or detection of estrus and
AI plus a clean-up TAI for heifers not detected in estrus, and whether adding an
injection of GnRH at controlled internal drug release (CIDR) insertion would
enhance fertility in CIDR-based protocols. Estrus in 2,075 replacement beef
heifers at 12 locations was synchronized, and AI was preceded by 1 of 4
treatments arranged as a 2 x 2 factorial design: 1) Estrus detection + TAI (ETAI)
(n = 516): CIDR for 7 d plus 25 mg of prostaglandin F2alpha (PG) at CIDR insert
removal, followed by detection of estrus for 72 h and AI for 84 h after PG
(heifers not detected in estrus by 84 h received 100 microg of GnRH and TAI); 2)
G+ETAI (n = 503): ETAI plus 100 microg GnRH at CIDR insertion; 3) Fixed-time AI
(FTAI) (n = 525): CIDR for 7 d plus 25 mg of PG at CIDR removal, followed in 60 h
by a second injection of GnRH and TAI; 4) G+FTAI (n = 531): FTAI plus 100 microg
of GnRH at CIDR insertion. Blood samples were collected (d -17 and -7, relative
to PG) to determine ovarian status. For heifers in ETAI and G+ETAI treatments, a
minimum of twice daily observations for estrus began on d 0 and continued for at
least 72 h. Inseminations were performed according to the a.m.-p.m. rule.
Pregnancy was diagnosed by transrectal ultrasonography. The percentage of heifers
exhibiting ovarian cyclic activity at the initiation of treatments was 89%.
Pregnancy rates among locations across treatments ranged from 38 to 74%.
Pregnancy rates were 54.7, 57.5, 49.3, and 53.1% for ETAI, G+ETAI, FTAI, and
G+FTAI treatments, respectively. Although pregnancy rates were similar among
treatments, a tendency (P = 0.065) occurred for pregnancy rates in the G+ETAI
treatment to be greater than in the FTAI treatment. We concluded that the G+FTAI
protocol yielded pregnancy rates similar to protocols that combine estrus
detection and TAI. Further, the G+FTAI protocol produced the most consistent
pregnancy rates among locations and eliminated the necessity for detection of
estrus when inseminating replacement beef heifers.
PMID- 17032796
TI - Impact of corn vitreousness and processing on site and extent of digestion by
feedlot cattle.
AB - Eight cannulated Holstein steers (average BW: 251 kg) were used in 2 simultaneous
4 x 4 Latin squares in a split-plot arrangement to test the effects of processing
method [dry-rolled (DR) vs. steam-flaked (SF); main plot] and vitreousness (V, %;
subplot) of yellow dent corn (V55, V61, V63, and V65) on site of digestion of
diets containing 73.2% corn grain. No vitreousness x processing method
interactions were detected for ruminal digestion, but ruminal starch digestion
was 14.4% lower (P < 0.01) for DR than for SF corn. Interactions were detected
between vitreousness and processing method for postruminal (P < 0.10) and total
tract digestion (P < 0.05). With DR, vitreousness tended to decrease (linear
effect, P < 0.10) postruminal OM and starch digestion. With SF, vitreousness did
not affect (P > or = 0.15) postruminal digestion of OM and starch. Postruminal N
digestion tended to decrease (linear effect, P = 0.12) as vitreousness increased.
Postruminal digestion was greater for SF than for DR corn OM (25.7%, P < 0.05),
starch (94.3%, P < 0.10), and N (10.7%, P < 0.01). Steam flaking increased total
tract digestion of OM (11%, P < 0.05), starch (16%, P < 0.01), and N (8.4%, P <
0.05) but decreased total tract ADF digestion (26.7%, P < 0.01). With DR, total
tract starch digestion was lower for V65 (cubic effect, P < 0.10) than for the
other hybrids. With SF, total tract starch digestion was not affected (P > or =
0.15) by vitreousness. Fecal starch and total tract starch digestion were
inversely related (starch digestion, % = 101 - 0.65 x fecal starch, %; r2 = 0.94,
P < 0.01). Ruminal pH was greater for steers fed DR than for steers fed SF corn
(6.03 vs. 5.62, P < 0.05). Steam flaking decreased (P < 0.01) the ruminal molar
proportion of acetate (24%), acetate:propionate molar ratio (55%), estimated
methane production (37.5%), and butyrate (11.3%, P < 0.05). There was a
vitreousness x processing interaction (P < 0.01) for acetate:propionate. For DR,
acetate:propionate tended to increase (linear effect; P < 0.10) with increasing
vitreousness. With SF, acetate:propionate was greater (cubic effect, P < 0.01)
for V65. Starch from more vitreous corn grain was less digested when corn grain
was DR, but this adverse effect of vitreousness on digestion was negated when the
corn grain was SF. Of the 19% advantage in energetic efficiency associated with
flaked over rolled corn grain, about 3/4 can be attributed to increased OM
digestibility, with the remaining 1/4 ascribed to reduced methane loss.
PMID- 17032797
TI - Effects of phase feeding of protein on performance, blood urea nitrogen
concentration, manure nitrogen:phosphorus ratio, and carcass characteristics of
feedlot cattle.
AB - Two experiments with a randomized complete block design were conducted to
determine the effects of phase feeding of CP on performance, blood urea nitrogen
(BUN), manure N:P ratio, and carcass characteristics of steers fed in a feedlot.
In Exp. 1, 45 crossbred steers (initial BW = 423 +/- 3.3 kg) were individually
fed a diet formulated to contain 13.0% CP (DM basis) for 62 d. On d 63, the
dietary CP was maintained at 13.0% or formulated to contain 11.5 or 10.0% CP
until slaughter. Actual CP values were 12.8, 11.8, and 9.9%, respectively.
Reducing the CP concentration of the diet did not affect ADG of steers from d 62
to 109 (P = 0.54) or over the 109-d feeding period (1.45, 1.50, and 1.49 kg/d for
13.0, 11.5, and 10.0% CP, respectively; P = 0.85). No differences (P > 0.12)
among treatments were detected for BUN concentrations on d 0, 62, or 109.
Gain:feed, DMI, and carcass characteristics did not differ among treatments (P >
0.10). In Exp. 2, 2 trials were conducted using 184 (initial BW = 406 +/- 2.6 kg)
and 162 (initial BW = 342 +/- 1.9 kg) crossbred steers. Data from the 2 trials
were pooled for statistical analysis, and trial effect was added to the
statistical model. Steers were fed a diet formulated to contain 13.0% CP until
reaching approximately 477 kg. When the average BW of the pen was 477 kg, diets
were maintained at 13.0% CP or reduced to contain 11.5 or 10.0% CP. Actual CP
values were 12.4, 11.5, and 9.3% CP for treatments 13.0, 11.5, and 10.0% CP,
respectively. Reducing the CP content of the diet did not affect ADG after the
diet changed (P = 0.16) or throughout the finishing period (P = 0.14).
Immediately before slaughter, steers fed the 13.0% CP diet had greater (P <
0.001) BUN concentrations than steers fed the 11.5 and 10.0% CP diets. Carcasses
from cattle fed the 11.5% CP diet had greater (P = 0.02) fat thickness than the
13.0 and 10.0% CP treatments, whereas carcasses from cattle fed 13.0% CP had
greater (P = 0.004) marbling scores than steers fed the 11.5 or 10.0% CP diets.
Other carcass characteristics, DMI, and G:F did not differ (P > 0.10) among
treatments. The N:P ratio was increased with the 10.0% CP diet (P = 0.02)
compared with the 11.5 or 13.5% CP treatments; however, manure composition did
not differ (P > 0.10) among treatments. These results indicate that reduced CP
concentration during the finishing period does not affect feedlot performance but
can improve the N and P relationship in the manure.
PMID- 17032798
TI - Increasing the amount of n-3 fatty acid in meat from young Holstein bulls through
nutrition.
AB - Fifty-four Holstein bulls were blocked by initial BW (301 +/- 7.4 kg) and
randomly assigned to 6 treatments following a 3 x 2 factorial arrangement, with 3
concentrate lipid levels (5, 8, and 11% of DM) and 2 lipid sources (whole canola
seed and whole linseed), with the objective of evaluating the possibility of
increasing the content of n-3 fatty acids in meat. Concentrates (mostly corn
meal) were isonitrogenous and isocaloric. Concentrate and straw were both fed ad
libitum. Animal BW was recorded every 2 wk, and feed consumption was recorded
weekly. Ruminal pH and VFA concentrations were determined monthly. Bulls were
transported to the slaughterhouse when they achieved the target slaughter weight
of 443 kg (after 105 +/- 4 d of fattening). After slaughter, a sample of LM from
the sixth to the eighth ribs was dissected and analyzed for intramuscular fat
content and fatty acid profile. Dietary lipid source did not affect overall
animal performance, rumen fermentation, or carcass quality. Rumen pH was >6.0
despite consumption by the bulls of large amounts of concentrate. In bulls fed
linseed, the percentage of n-3 fatty acids in LM increased linearly with lipid
level, whereas in bulls fed canola seed it remained constant. The ratio of n-6:n
3 fatty acids was lower (P < 0.01) in the LM of bulls fed linseed (10.0) than in
those fed canola seed (26.0). The content of cis-9, trans-11-CLA in the LM tended
(P = 0.06) to be greater in the bulls fed linseed than in those fed canola seed
(62.9 vs. 49.2 mg/kg of LM, respectively). Concentration of n-3 fatty acids in
meat of bulls fed high-concentrate diets can be enhanced by whole linseed
supplementation without affecting animal performance, ruminal fermentation, or
carcass quality.
PMID- 17032799
TI - Effects of high-sugar ryegrass silage and mixtures with red clover silage on
ruminant digestion. 1. In vitro and in vivo studies of nitrogen utilization.
AB - Two experiments were carried out to determine the effects of feeding grass
silages differing in their water-soluble carbohydrate content, with or without
red clover silage, on the efficiency of nutrient use. High-sugar grass, control
grass, and red clover were ensiled in laboratory silos for use in an in vitro
experiment (Exp. 1). For an in vivo experiment (Exp. 2), the same forage types
were baled and ensiled. All silages were well preserved; within experiments the
grass silages had similar composition, except for greater (P < 0.05) water
soluble carbohydrate concentrations in the high-sugar than the control grass
silage. In Exp. 1, high-sugar grass, control grass, and red clover silages were
fed alone or as mixtures (30:70, 50:50, or 70:30 on a DM basis, respectively) of
each grass with the red clover silage to a simulated rumen culture system. There
were no significant differences in microbial N flow or efficiency of microbial
protein synthesis between individual forages. However, the corresponding values
for the 70:30 ratio of high-sugar grass:red clover silage were greater (P < 0.05)
than for the red clover silage. The value for the efficiency of N use (g of
microbial N/g of feed N) was greater (0.86; P < 0.05) for high-sugar grass silage
than the control grass silage. In addition, the high-sugar grass:red clover
silage mixtures all gave greater (P < 0.05) values for the efficiency of N use
than red clover silage alone; this difference was not achieved with the control
grass mixture. Experiment 2 was an incomplete Latin square design conducted with
6 Here-ford x Friesian steers (163 +/- 5.9 kg of BW) with rumen and duodenal
cannulas fed the following 5 silage diets: high-sugar grass silage; control grass
silage; high-sugar grass and red clover silage (50:50 DM basis); control grass
and red clover silage (50:50 DM basis); and red clover silage. Rumen NH3-N
concentration was lowest (P < 0.05) with the high-sugar grass silage. Microbial N
flows to the duodenum and efficiency of microbial protein synthesis were greater
(P < 0.05) for steers fed the high-sugar grass silage than for control grass and
red clover silages, and mixing red clover with grass silages increased (P < 0.05)
these values compared with red clover silage alone. In both experiments, the
efficiency of incorporation of silage N into microbial N was more than 20%
greater (P < 0.05) for high-sugar grass than for control grass silage. These data
suggest that grass silage with high-sugar content provides a forage-based
strategy for balancing N and energy supply and improving the efficiency of use of
grass silage N in the rumen.
PMID- 17032800
TI - Effects of high-sugar ryegrass silage and mixtures with red clover silage on
ruminant digestion. 2. Lipids.
AB - The experiment investigated the digestion of lipids from different forage silages
in beef steers. Six Hereford x Friesian steers prepared with rumen and duodenal
cannulas were given ad libitum access to a high-sugar grass silage, control grass
silage, red clover silage, or mixtures of the red clover and each of the grass
silages (50:50, DM basis). The experiment was conducted as an incomplete 5 x 5
Latin square, with an additional randomly repeated sequence. Total fatty acid and
C18:3n-3 concentrations were greater (P < 0.05) for the high-sugar grass silage
than the control grass silage or the red clover silage. Dry matter and total
fatty acid intake were less (P < 0.05) for steers fed the control grass silage
than for steers fed the other diets. Duodenal flow of C18:3n-3 was greater (P <
0.05), and flows of C18:0 and total C18:1 trans were less (P < 0.05), for the red
clover silage compared with the 2 grass silage diets, with the mixtures
intermediate. These results were supported by a reduction (P < 0.05) in
biohydrogenation of C18:3n-3 for the red clover silage, with the mixtures again
being intermediate. Flows of total branched- and odd-chain fatty acids were
greater (P < 0.05) for the high-sugar grass silage diet, possibly as a result of
greater microbial flow, because these fatty acids are associated with bacterial
lipid. Duodenal flows of the chlorophyll metabolite, phytanic acid, were greater
(P < 0.05) for animals fed the high-sugar grass silage treatments compared with
the other treatments. These results confirm the potential for modifying the fatty
acid composition of ruminant products by feeding red clover silage.
PMID- 17032801
TI - Effect of dietary vitamin E supplementation and feeding period on pork quality.
AB - Feeding increased levels of dietary vitamin E can inhibit lipid oxidation. The
aim of this study was to investigate the effect of levels of dietary alpha
tocopherol acetate (VE) and feeding duration on meat quality and lipid oxidation.
Eighty-one pigs were allocated to 1 of 3 diets containing 40, 200, or 400 IU of
VE/kg of feed, and each diet group was divided into 3 feeding periods (3, 6, or 9
wk). Carcass characteristics and meat quality were evaluated. Oxidative stability
of fresh and cooked pork patties and pork chops was determined after chilled or
frozen storage. Increasing dietary concentrations of VE did not affect any growth
performance parameter. Drip loss, however, decreased (P < 0.05) with increased
dietary VE levels. Moreover, an increased duration of VE feeding improved (P <
0.05) pH and drip loss. Less lipid oxidation (P < 0.05) was detected in fresh
ground pork from pigs fed greater concentrations of VE after 4 d of storage. A
greater (P < 0.05) resistance to oxidation in cooked ground pork was observed in
pigs fed 200 or 400 IU of VE/kg at 2 and 6 d of storage. Fresh and cooked pork
patty oxidation decreased (P < 0.05) linearly as feeding duration increased from
3 to 9 wk. After 6 mo of freezer storage, lipid oxidation of pork chops from pigs
fed 200 or 400 IU of VE/kg was lower (P < 0.05) than for pigs fed 40 IU of VE/kg.
Likewise, lipid oxidation of pork chops of pigs fed VE for an extended period of
time (6 wk) was lower (P < 0.05) after 9 mo of storage. Fatty acid profiles of
neutral lipid fraction of the LM became more unsaturated (P < 0.05) with added VE
to the feed. These results indicate an increased intake of dietary VE
concentration, and prolonged feeding of VE can improve drip loss and reduce lipid
oxidation in ground pork and pork chops. This study suggests that supplementation
with 200 IU of VE/kg of feed for 6 wk before market is beneficial in improving
lipid stability and pork quality.
PMID- 17032802
TI - Treadmill exercise is not an effective methodology for producing the dark-cutting
condition in young cattle.
AB - Holstein steer calves (n = 25) were used to evaluate the effects of treadmill
exercise (TME) on blood metabolite status and formation of dark-cutting beef.
Calves were blocked by BW (156 +/- 33.2 kg) and assigned randomly within blocks
to 1 of 5 TME treatments arranged in a 2 x 2 factorial design (4 or 8 km/h for a
duration of 10 or 15 min) with a nonexercised control. Venous blood was collected
via indwelling jugular catheters at 10, 2, and 0 min before TME and at 2-min
intervals during exercise. Nonexercised steers were placed on the treadmill but
stood still for 15 min. Serum cortisol levels, as well as plasma concentrations
of glucose, lactate, and NEFA, were similar (P > 0.05) before TME. Serum cortisol
concentrations were unaffected (P > 0.05) during the first 6 min of TME, but
between 8 and 15 min of TME, cortisol concentrations were greater (P < 0.05) in
steers exercised at 8 km/h than those exercised at 4 km/h or controls (speed x
time, P < 0.001). Although TME did not affect (P > 0.05) plasma glucose levels,
plasma lactate concentrations in steers exercised at 8 km/h increased (P < 0.05)
sharply with the onset of the TME treatment and remained elevated compared with
steers exercised at 4 km/h or unexercised controls (speed x time, P < 0.001).
Exercised steers had the lowest (P < 0.05) plasma NEFA concentrations during the
first 6 min of TME compared with unexercised steers; however, NEFA concentrations
were similar after 10 and 12 min of TME, and by the end of TME, steers exercised
at 8 km/h had greater (P < 0.05) NEFA levels than nonexercised controls or steers
exercised at 4 km/h (speed x time, P < 0.001). Even though muscle glycogen levels
and pH decreased (P < 0.001) and muscle lactate concentrations increased (P <
0.001) with increasing time postmortem, neither treadmill speed nor TME duration
altered postmortem LM metabolism. Consequently, there were no (P > 0.05)
differences in the color, water-holding capacity, shear force, or incidences of
dark-cutting carcasses associated with preslaughter TME. It is apparent that
preslaughter TME, at the speeds and durations employed in this study, failed to
alter antemortem or postmortem muscle metabolism and would not be a suitable
animal model for studying the formation of the dark-cutting condition in
ruminants.
PMID- 17032803
TI - Effects of dietary vitamin E and fat supplementation on pork quality.
AB - The effects of dietary vitamin E (VE, alpha-tocopherol acetate) and fat
supplementation on growth and carcass quality characteristics, oxidative
stability of fresh and cooked pork patty in storage, fatty acid profiles of
muscle and adipose tissue, and VE concentrations of plasma, muscle, and adipose
tissue were studied. Six hundred pigs were allocated to 1 of 6 diets and fed for
63 d in a 3 x 2 factorial design. The dietary treatments included 3 fat levels
(normal corn, high oil corn, high oil corn plus added beef tallow) and 2 levels
of VE supplementation (40 IU/kg, normal VE supplementation; and 200 IU/kg, high
VE supplementation). At 113 kg of BW, 54 pigs were slaughtered as a subsample to
evaluate dietary effects on pork quality. Growth performance and meat quality
characteristics did not differ (P > 0.05) among treatment groups. The high level
of VE supplementation had a beneficial effect on the oxidative stability of pork
as indicated by thiobarbituric acid reactive substance (TBARS) values. Lean
tissue had lower (P < 0.05) TBARS in the group fed the high VE than in those fed
the normal VE level. The TBARS values differed among storage periods (0 to 6 d)
and also between fresh and cooked ground ham. Fat type did not significantly
affect total saturated and unsaturated fatty acids proportions in the neutral and
polar fraction of muscle. Adding VE acetate led to greater (P < 0.05)
monounsaturated and total unsaturated fatty acid proportions in neutral lipids of
muscle and adipose tissues. Increasing dietary levels of VE acetate increased the
concentration of VE in plasma and muscle. These results indicate that dietary VE
acetate supplementation increased (P < 0.05) lipid stability and the VE
concentration of muscle.
PMID- 17032804
TI - Technical note: Exit velocity as a measure of cattle temperament is repeatable
and associated with serum concentration of cortisol in Brahman bulls.
AB - The objectives of this study were 1) to compare temperament assessments, using
multiple techniques and over repeated observations, to gauge temperament over the
long-term and 2) to evaluate the relationship of the temperament appraisals with
serum concentrations of cortisol (CS). Measures of temperament were gathered over
3 repeated observations (60-d interval) of yearling, fall-born Brahman bulls
(initial BW = 320 +/- 4 kg; n = 66). Temperament assessments included exit
velocity (EV), which was the rate at which the bulls exited the squeeze chute and
traversed a fixed distance (1.83 m); pen scores (PEN; 1 = quiet to 5 = excited),
ascertained from animal behavior while penned in small groups (n = 5); and chute
scores (CHUTE; 1 = quiet to 5 = excited), determined from behavioral responses to
restraint on the weigh scale. Temperament measures obtained during the initial
data collection (d 0) were all positively correlated (r > or = 0.35, P < 0.005)
with one another. Additionally, PEN (r = 0.29, P < 0.05) and EV (r = 0.26, P <
0.05) were positively correlated with CS, whereas CHUTE was not (r = 0.09, P =
0.46). All serial EV measures were positively correlated (r > 0.31, P < 0.02).
All PEN were positively correlated (r > 0.31, P < 0.01), whereas serial measures
of CHUTE were not (P > 0.3). Exit velocity was positively correlated with CS
within d 0 (r = 0.26, P = 0.04) and 120 (r = 0.44, P < 0.01). The EV data
obtained at d 0 were transformed into a discrete variable, EV ranking (EV RANK; 1
to 3 scale), in which 1 equated to <1 SD below the mean and 3 equated to >1 SD
above the mean. Mean EV (P < 0.01) decreased from d 0 (2.82 +/- 0.07 m/sec) to
120 (2.11 +/- 0.10 m/sec). Time also influenced (P < 0.01) CS; mean CS decreased
between d 0 (14.6 +/- 0.7 ng/mL) and 120 (11.1 +/- 0.8 ng/mL). Measures of EV can
be a valuable tool for the assessment of cattle temperament and a possible
predictor of temperament and stress responsiveness to future animal handling
events.
PMID- 17032805
TI - Voluntary intake and digestibility of reed canarygrass and timothy hay fed to
horses.
AB - Thousands of hectares of timothy (Phleum pretense L.) grown in the Mid-Atlantic
region are infected by cereal rust mite (Abacarus hysterix) that causes
discoloration and curling of leaves, decreased nutritional quality, and
substantial decreases in yield. A decline in production of timothy hay can lower
income for hay producers and cause horse owners to search for alternative hays.
Low alkaloid reed canarygrass (Phalaris arundinacea L.) hay has potential as an
alternative to timothy hay because it grows well in the Mid-Atlantic region, is
believed to have a similar nutrient quality to timothy, and is not as susceptible
to cereal rust mite. Eleven mature, stalled Thoroughbred geldings (549 +/- 12.1
kg) that were exercised daily were used to compare voluntary DMI and apparent
nutrient DM digestibility of timothy and low-alkaloid Chiefton variety reed
canarygrass hay. Horses were paired by age and BW and randomly assigned to
timothy or reed canarygrass hay during a 14-d period to measure voluntary DMI
followed by a 4-d period to measure apparent DM digestibility. Both hays met the
minimum requirements for DE, CP, Ca, P, K, Fe, and Mn, but they did not meet the
minimum requirements for Cu, Zn, and Na for horses at maintenance and averaging
550 kg of BW. Timothy hay seemed to have a lower CP concentration (14.4%)
compared with reed canarygrass hay (17.1%) and a more desirable Ca:P ratio at
1.6:1 compared with 0.8:1 for reed canarygrass hay. Horses fed timothy consumed
more hay (P <0.001) during the voluntary DMI period compared with horses fed reed
canarygrass. Greater voluntary DMI of timothy occurred on d 1, 3, and 5 (P
<0.05), but DMI was similar for other days. Apparent DM digestibility was greater
in horses fed timothy hay by 9.6% compared with horses fed reed canarygrass hay
(P <0.05). Horses fed timothy had greater DM digestibility of ADF (P = 0.001),
NDF (P = 0.001), sugar (P = 0.05), and Ca (P = 0.001) but lower apparent DM
digestibility of CP (P = 0.012) and crude fat (P = 0.004). Timothy hay was
superior in voluntary DMI and apparent DM digestibility compared with low
alkaloid reed canarygrass hay fed to horses.
PMID- 17032806
TI - The influence of dietary field peas (Pisum sativum L.) on pig performance,
carcass quality, and the palatability of pork.
AB - An experiment was conducted to test the hypothesis that field peas may replace
soybean meal in diets fed to growing and finishing pigs without negatively
influencing pig performance, carcass quality, or pork palatability. Forty-eight
pigs (initial average BW 22.7 +/- 1.21 kg) were allotted to 1 of 3 treatments
with 2 pigs per pen. There were 8 replications per treatment, 4 with barrows and
4 with gilts. The treatments were control, medium field peas, and maximum field
peas. Pigs were fed grower diets for 35 d, early finisher diets for 35 d, and
late finisher diets for 45 d. Pigs receiving the control treatment were fed corn
soybean meal diets. All diets fed to pigs receiving the medium field peas
treatment contained 36% field peas and varying amounts of corn; soybean meal was
also included in the grower and the early finisher diets fed to pigs on this
treatment. In contrast, no soybean meal was included in diets fed to pigs on the
maximum field peas treatment, and field peas were included at concentrations of
66, 48, and 36% in the grower, early finisher, and late finisher diets,
respectively. Pig performance was monitored within each phase and for the entire
experimental period. At the conclusion of the experiment, carcass composition,
carcass quality, and the palatability of pork chops and pork patties were
measured. Results showed that there were no effects of dietary treatments on
ADFI, ADG, or G:F. Likewise, there were no differences in carcass composition
among the treatment groups, but gilts had larger (P = 0.001) and deeper (P =
0.003) LM, less backfat (P = 0.007), and a greater (P = 0.002) lean meat
percentage than barrows. The pH and marbling of the LM, and the 10th rib backfat
were not influenced by treatment, but there was a trend (P = 0.10) for more
marbling in barrows than in gilts. The subjective color scores (P = 0.003) and
the objective color score (P = 0.06) indicated that dietary field peas made the
LM darker and more desirable. Pork chops from pigs fed field peas also had less
(P = 0.02) moisture loss compared with chops from pigs fed the control diet.
Treatment or sex did not influence palatability of pork chops or pork patties. In
conclusion, field peas may replace all of the soybean meal in diets fed to
growing and finishing pigs without negatively influencing pig performance,
carcass composition, carcass quality, or pork palatability.
PMID- 17032807
TI - Effect of timing of feeding a high-concentrate diet on growth and attainment of
puberty in early-weaned heifers.
AB - Precocious puberty (<300 d of age) can be successfully induced in a majority of
heifers with early weaning and continuous feeding of a high-concentrate diet. The
objective of this experiment was to determine the relative effects of timing of
feeding a high-concentrate diet on age at puberty in early-weaned heifers. Sixty
crossbred Angus and Simmental heifer calves were weaned at 112 +/- 2 d of age and
155 +/- 3 kg of BW and were fed a receiving diet for 2 wk. Heifers were blocked
by age and BW, and assigned randomly to receive a high-concentrate (60% corn; H)
or control (30% corn; C) diet during phase 1 (mean age 126 to 196 d) and H or C
during phase 2 (mean age 196 to 402 d), resulting in 4 treatments (HH, n = 15;
HC, n = 15; CH, n = 15; and CC, n = 15). Blood samples were collected weekly
beginning at a mean age of 175 d and assayed for progesterone concentration to
determine age at puberty. After 56 d on the experimental diets, BW of heifers fed
the H diet during phase 1 were greater (P < 0.05) than those of heifers fed the C
diet (mean age of 182 d; treatment x mean age, P < 0.01). After 70 d on the new
diets (mean age of 266 d), heifers fed the H diet during phase 2 reached heavier
BW (P < 0.05) than heifers fed the C diet, when compared within phase 1 diet
groups (HH > HC; CH > CC). Body weights in HC and CH treatments differed from a
mean age of 169 through 238 d, after which BW did not differ between these
treatments. The ADG over the entire experimental period was greatest for the HH
treatment (1.2 +/- 0.04 kg/d; P < 0.05), followed by the HC and CH treatments
(1.0 +/- 0.03 and 1.0 +/- 0.02 kg/d, respectively), which were not different, and
the CC treatment gained the least (0.7 +/- 0.04 kg/d; P < 0.05). Precocious
puberty occurred in 67, 47, 47, and 20% of heifers in the HH, HC, CH, and CC
treatments, respectively (HH > CC; P < 0.05). Mean age at puberty for the HH and
HC treatments (271 +/- 17 and 283 +/- 17 d of age, respectively) was earlier (P <
0.05) than for the CC treatment (331 +/- 11 d of age). Age at puberty in the CH
treatment (304 +/- 13 d of age) was intermediate to and not different from the
other treatments. Heifers fed the H diet during phase 1 attained puberty earlier
(P < 0.05) than heifers fed the C diet during phase 1. In conclusion, increasing
dietary energy intake in early-weaned heifers, through feeding a high-concentrate
diet from 126 to 196 d of age, decreased age at puberty regardless of the diet
fed after 196 d of age.
PMID- 17032808
TI - Effect of diet composition on water consumption in growing pigs.
AB - Concerns relating to use of water resources by the livestock industry, combined
with the rising cost of manure management, have resulted in greater interest in
identifying ways to reduce drinking water utilization by pigs while maintaining
animal well-being and achieving satisfactory growth performance. The objective of
this experiment was to determine if increasing the dietary CP or mineral
concentrations increases water intake and excretion and, conversely, if reducing
the dietary CP content reduces water intake and excretion. Forty-eight barrows
(34.3 +/- 4.6 kg of BW; 12/treatment) were given free access to diets containing
a low protein (16.9% CP), high protein (20.9% CP), or excess protein (25.7% CP)
level, or a diet with excess levels of Ca, P, Na, and Cl. Water was available to
each pig on an ad libitum basis via dish drinkers that were determined to waste
less than 3% of total water flow. The excess CP diet tended to increase average
daily water intake (ADWI) and urinary excretion (P < 0.10) and increased the
water:feed ratio (P < 0.05); lowering dietary CP did not lower water intake or
excretion. The excess mineral diet did not increase ADWI or urinary excretion but
did increase water excretion via the feces. Daily nutrient intake and dietary
nutrient concentration were poor predictors of ADWI; only daily intake of N and K
were significantly correlated with ADWI (P < 0.05), and the r-values were low
(0.39 and 0.32, respectively). There was no relationship between ADFI and ADWI.
The average water:feed ratio was 2.6:1. Any study of water utilization is
complicated by behavioral as well as nutritional and physiological influences,
and isolating physiological need from so-called luxury intake is a significant
experimental challenge. Because the impact of dietary treatment on water
utilization was small, we conclude that factors other than dietary protein and
mineral concentration and daily protein and mineral intake have a relatively
large effect on water intake and excretion. Consequently, strategies to reduce
water intake must recognize, understand, and manage these additional behavioral
and physiological factors. Diet composition may be a part of strategies designed
to reduce excessive water utilization by the pig industry but may have a limited
effect if other important factors are ignored.
PMID- 17032809
TI - In vivo mechanical and in vitro electromagnetic side-effects of a ruminal
transponder in cattle.
AB - This work was undertaken to assess the long-term impacts of a ruminal
transponder, used for electronic identification, on ruminal motility and on
health and performance of cattle, as well as to study the electromagnetic effects
on ruminal bacteria in vitro. A passive transponder (51.4 g, 67 x 17 mm) was
delivered into the forestomachs of 8 calves, 32 bulls, 10 heifers, and 40 dairy
cows. Final readability was 87.5% in calves, 96.9% in bulls, 90% in heifers, and
100% in cows at 481, 360, 650, and 601 d, respectively, after transponder
administration. The transponder did not affect production or reproduction of cows
over a 2-yr period, or performance of bulls, or mortality compared with control
animals. Chewing movements per bolus were lower (P <0.01) in treated animals than
in controls (49.6 vs. 52.2, 51.2 vs. 63.6, and 57.0 vs. 59.7 for bulls, heifers,
and cows, respectively). Regurgitation frequency (number of boluses/10 min)
tended to be greater in treated cattle: 12.4 vs. 11.3 (P = 0.07), 11.3 vs. 10.6,
and 11.3 vs. 10.7 (P = 0.08) for bulls, heifers, and cows, respectively.
Rumination patterns of calves fitted with transponders within the first weeks of
life were similar to controls. During the experiment, 43 treated animals (8
calves, 29 bulls, and 6 cows) were slaughtered. Thirty transponders were
localized in the reticulum (3 calves, 24 bulls, and 3 cows), 11 in the rumen (4
calves, 4 bulls, and 3 cows), and 2 were not recovered (1 calf and 1 bull).
Within the calves, 57% of the boluses were found in the rumen. In 8 reticula (2
calves and 6 bulls) and 1 rumen (1 cow), an impression left by physical contact
of the transponder was observed, although histological examination did not reveal
specific lesions in the mucosa of the dystrophic areas. In strained, whole
ruminal contents incubated in vitro, pH values were lower after 24 and 48 h (P
<0.001) of continuous exposure to an electromagnetic field induced by the
transponder-reading system. After 48 h of incubation, total bacterial numbers and
NH3-N concentration were greater (P <0.001) in exposed flasks than in controls.
These data indicate that the transponder may alter, via mechanical action, the
reticuloruminal mucosa and rumination patterns. Furthermore, the transponder may
increase, via its electromagnetic action, the growth rate and metabolic activity
of ruminal bacteria.
PMID- 17032810
TI - Meta-analysis of factors affecting carcass characteristics of feedlot steers.
AB - A meta-analysis was conducted to assess the effects of biological type (early
moderate or late maturity) and implant status (estrogenic, combination, or
nonimplanted; repeats included) on HCW (kg); LM area (cm2); 12th-rib fat
thickness (fat thickness, cm); KPH (%), and intramuscular fat (%) at harvest, to
provide inputs to an ongoing program for modeling beef cattle growth and carcass
quality. Forty-three publications from 1982 to 2004 with consistent intramuscular
fat data were evaluated. Two studies were undertaken: 1) with fat thickness as a
covariate and 2) with BW as a covariate. The intercept-slope covariance estimate
was not statistically different from 0 for LM area (P = 0.11), KPH (P = 0.19),
and intramuscular fat (P = 0.74) in study 1, and for LM area (P = 0.44), fat
thickness (P = 0.11), KPH (P = 0.19), and intramuscular fat (P = 0.74) in study
2; therefore, a reduced model without a covariance component was fitted for these
carcass characteristics. A covariance component was fitted for HCW (P = 0.01,
study 1 and P = 0.05, study 2) and for intramuscular fat (P = 0.05, study 2). In
study 1, the results for maturity indicated differences between early-moderate
and late maturity for HCW (P < 0.01) and LM area (P < 0.01) but no differences
for KPH (P = 0.26) and intramuscular fat (P = 0.50); for implant status, an
estrogenic or combination implant increased HCW by 2.9% (P = 0.27) or 4.8% (P <
0.01), increased LM area by 3.2% (P = 0.23) or 6.3% (P < 0.01), decreased
intramuscular fat by 8.1% (P < 0.01) or 5.4% (P < 0.01), respectively, and
decreased KPH by 7.6% (P = 0.34) for estrogenic implants but increased KPH by
1.1% (P = 0.36) for combination implants, compared with nonimplanted steers. In
study 2, the results at 600 kg of BW for implant status (implant or nonimplant)
indicated no differences for HCW (P = 0.63) and LM area (P = 0.73), but there
were differences for fat thickness (P < 0.01), KPH (P < 0.01), and intramuscular
fat (P < 0.01); the results for maturity (early-moderate or late maturity)
indicated no differences for HCW (P = 0.94), but there were differences for LM
area (P < 0.01), fat thickness (P < 0.01), KPH (P < 0.01), and intramuscular fat
(P < 0.01). The difference between early-moderate and late maturity (studies 1
and 2) confirmed that frame size accounts for a substantial portion of the
variation in carcass composition. Studies 1 and 2 also indicate that implant
status had significant effects on carcass quality.
PMID- 17032811
TI - Interindividual variability in plasma concentrations after systemic exposure of
swine to dietary doxycycline supplied with and without paracetamol: a population
pharmacokinetic approach.
AB - Anorexigenic substances released during infection may hinder the therapeutic
efficacy of in-feed antibiotics. Paracetamol (acetaminophen; PARA) inhibits the
anorexia of infection and seems to improve the clinical efficacy of doxycycline
(DOX) against bacterial respiratory disease in swine herds. In order to verify
whether PARA selectively stimulates intake of DOX-medicated feed in diseased
pigs, we documented the pharmacokinetics (PK) of DOX when coadministered with
PARA and examined the effect of in-feed PARA on the interindividual variability
in plasma concentrations after systemic exposure to in-feed DOX in swine herds
with respiratory disease. Systemic exposure to DOX was measured with the area
under the curve (AUC) of its plasma concentrations over time. First, a rich
sampling PK study of in-feed and i.v. DOX (10 mg/kg of BW) and PARA (30 and 10
mg/kg of BW, respectively) was performed on 5 pigs. The PK profiles of in-feed
DOX were used in mathematical simulations to determine 5 optimal sampling times
for the farm-based population PK study. A randomized, blind, parallel PK study
was performed in 2 herds with bacterial respiratory disease, where liquid feed
was fortified with DOX alone (5 mg x kg of BW(-1) x meal(-1)) or combined with
PARA (15 mg x kg of BW(-1) x meal(-1)). Medicated meals were given twice, 12 h
apart, to group-housed growing pigs (n > 50 pigs x treatment(-1) x herd(-1),
totaling 215 pigs). Plasma concentrations of DOX and PARA were measured with
HPLC. At variance with our expectations, PARA decreased (P = 0.069) mean AUC of
in-feed DOX and did not decrease its variability (P > 0.34). Mean AUC of DOX
increased with feed intake and with initial exposure to DOX, and was greater in
sick animals. Therefore, symptomatic PARA-induced improvement in bacterial
respiratory disease control with DOX is more likely caused by its
analgesic/antipyretic effects than by its orexigenic effect. Interindividual
variation in the AUC of DOX was large in pigs given group medication, even when
sufficient feeding space was allowed and the amount of feed offered was greater
than their requirements. Therefore, future studies to improve the efficacy of
group antibiotic therapy should focus on feeding behavior characteristics as well
as biopharmaceutical properties of medicated feeds.
PMID- 17032813
TI - Fundamental questions about genes, inactivity, and chronic diseases.
AB - Currently our society is faced with the challenge of understanding the biological
basis for the epidemics of obesity and many chronic diseases, including Type 2
diabetes. Physical inactivity increases the relative risk of coronary artery
disease by 45%, stroke by 60%, hypertension by 30%, and osteoporosis by 59%.
Moreover, physical inactivity is cited as an actual cause of chronic disease by
the US Centers of Disease Control. Physical activity was obligatory for survival
for the Homo genus for hundreds of thousands of years. This review will present
evidence that suggests that metabolic pathways selected during the evolution of
the human genome are inevitably linked to physical activity. Furthermore, as with
many other environmental interactions, cycles of physical activity and inactivity
interact with genes resulting in a functional outcome appropriate for the
environment. However, as humans are less physically active, there is a
maladaptive response that leads to metabolic dysfunction and many chronic
diseases. How and why these interactions occur are fundamental questions in
biology. Finally, a perspective to future research in physical inactivity-gene
interaction is presented. This information is necessary to provide the molecular
evidence required to further promote the primary prevention of chronic diseases
through physical activity, identify those molecules that will allow early disease
detection, and provide society with the molecular information needed to counter
the current strategy of adding physical inactivity into our lives.
PMID- 17032812
TI - Assessment of vasoconstrictive potential of D-lysergic acid using an isolated
bovine lateral saphenous vein bioassay.
AB - Vasoconstriction has been associated with several symptoms of fescue toxicosis
thought to be alkaloid induced. Lysergic acid, an ergot alkaloid, has been
proposed as a toxic component of endophyte-infected tall fescue. The objective of
this study was to examine the vasoconstrictive potential of D-lysergic acid using
a bovine lateral (cranial branch) saphenous vein bioassay. Before testing
lysergic acid, validation of the bovine lateral saphenous vein bioassay for use
with a multimyograph apparatus was conducted using a dose-response to
norepinephrine to evaluate the effects of limb of origin (right vs. left) and
overnight storage on vessel contractile response. Segments (2 to 3 cm) of the
cranial branch of the lateral saphenous vein were collected from healthy mixed
breed cattle (n = 12 and n = 7 for the lysergic acid and norepinephrine
experiments, respectively) at local abattoirs. Tissue was placed in modified
Krebs-Henseleit, oxygenated buffer and kept on ice or stored at 2 to 8 degrees C
until used. Veins were trimmed of excess fat and connective tissue, sliced into 2
to 3-mm sections, and suspended in a myograph chamber containing 5 mL of
oxygenated Krebs-Henseleit buffer (95% O2, 5% CO2; pH = 7.4; 37 degrees C).
Tissue was allowed to equilibrate at 1 g of tension for 90 min before initiation
of treatment additions. Increasing doses of norepinephrine (1 x 10(-8) to 5 x 10(
4) M) or lysergic acid (1 x 10(-11) to 1 x 10(-4) M) were administered every 15
min after buffer replacement. Data were normalized as a percentage of the
contractile response induced by a reference dose of norepinephrine. Veins from
both left and right limbs demonstrated contractions in a dose-dependent manner (P
< 0.01) but did not differ between limbs. There were no differences in dose
response to norepinephrine between tissue tested the day of dissection and tissue
tested 24 h later. Exposure of vein segments to increasing concentrations of
lysergic acid did not result in an appreciable contractile response until the
addition of 1 x 10(-4) M lysergic acid (15.6 +/- 2.3% of the 1 x 10(-4) M
norepinephrine response). These data indicate that only highly elevated
concentrations of lysergic acid result in vasoconstriction. Thus, in relation to
the symptoms associated with vasoconstriction, lysergic acid may only play a
minor role in the manifestation of fescue toxicosis.
PMID- 17032814
TI - Genome-wide analysis of SPAK/OSR1 binding motifs.
AB - Based on the alignment of 12 sequences of protein motifs that interact with the
kinases SPAK (Ste20-related proline alanine-rich kinase) and OSR1 (oxidative
stress response 1), we performed genome-wide searches of the sequence
[S/G/V]RFx[V/I]xx[V/I/T/S]xx, where x represents any amino acid. The "Mus
musculus" search resulted in the identification of 131 mouse proteins containing
137 SPAK/OSR1 putative binding motifs. Similar numbers were found for human,
zebrafish, fruit fly, and worm. A little more than half of the mouse proteins
containing SPAK/OSR1 binding domains (53%) were also identified in the human
search, whereas approximately 17-18% of these common hits were identified in the
zebrafish search. The mouse proteins could be divided into two broad categories:
2/3 had an identified function, whereas 1/3 were either predicted or of unknown
function. The known proteins were grouped as transport proteins, other membrane
proteins, kinases, phosphatases, cytoskeletal, ribosomal, nuclear, enzymes, and
others. Analysis of the location of the SPAK/OSR1 binding motif within the
protein sequence revealed distribution throughout the entire length, but with
preference to the extreme amino- or carboxyl termini for a large number of
proteins. Analysis of the amino acid composition of the motifs revealed a
preponderance of serine residues at positions 5, 6, 7, and 8. In summary, our new
search found and thus confirms the 12 proteins previously shown to interact with
the kinases and identifies 119 potential new targets for SPAK and OSR1 in the
mouse proteome.
PMID- 17032815
TI - Effects of temperature during rearing and crating on stress parameters and meat
quality of broilers.
AB - Two trials were conducted to study the effects of heat stress during rearing
(trial 1) and crating (trial 2) on broiler stress parameters and fear, breast
meat quality, and nutrient composition. The relationships between stress
parameters and meat quality traits were also determined. Trial 1 consisted of 3
temperature treatments from 3 to 7 wk: control (temperature was 22 degrees C);
diurnal cyclic temperature (temperature was 28 degrees C from 1000 to 1700 h and
22 degrees C from 1700 to 1000 h); and constant high temperature (34 degrees C;
temperature was 34 degrees C). In trial 2, broilers from the control and 34
degrees C groups in trial 1 were used. Broilers in each group were placed in
transport cages. The 9 cages from the control group were divided into 3 groups
and placed into 3 rooms at 15, 22, or 34 degrees C for 2 h. The 3 cages from the
34 degrees C group were also held in the room at 34 degrees C (34-34 degrees C).
Diurnal cyclic temperature had no effect on BW up to 5 wk of age. The effect of
34 degrees C constant temperature on BW of broilers increased with age. Plasma
levels of glucose and albumin increased by 34 degrees C, but no dramatic change
in levels occurred when those broilers were crated at 34 degrees C. The
heterophil:lymphocyte (H:L) was higher for the 34-34 degrees C broilers and the
control broilers in the 34 degrees C room than those from the 22 and 15 degrees C
room. Breast muscle glycogen level decreased in broilers reared under diurnal
cyclic or high temperatures. A lower pH and higher lightness (L*) and redness
values and redness:yellowness were found in meat for broilers from both 34
degrees C and 34-34 degrees C groups. Higher H:L was associated with breast
muscle pH according to first-order polynomial regression. The H:L had a
significant effect on L* values, which were described by a second-order
polynomial regression. Blood glucose level was positively correlated with L* and
redness values. Duration of tonic immobility was neither influenced by rearing
and crating temperatures nor associated with meat quality parameters.
PMID- 17032816
TI - Evolution of the environmental contamination by thermophilic fungi in a turkey
confinement house in France.
AB - Fungal species constitute a major part of environmental contaminants in
facilities where animals are housed. The present investigation was aimed at
describing the relative abundances of fungal species and their concentrations in
a turkey confinement house in France. Fungal cultures from poultry feed, litter,
and air were undertaken every week throughout the 16-wk period of breeding. The
incubation temperature of 40 degrees C was selected to isolate thermophilic
fungal species (especially Aspergillus spp. and Candida albicans) that are
potentially pathogenic for birds. The 2 species Aspergillus fumigatus and
Aspergillus flavus were recovered at a mean of 10.5 and 37.0 cfu/m(3) of air
sampled, respectively. Individual samplings yielded concentrations of up to 150.0
cfu/m(3) for A. flavus in the first weeks of the investigation. Other fungal
species were recovered at a mean of 18.9 cfu/m(3) (maximum 36.3 cfu/m(3)) in the
air. The yeast C. albicans was first detected at wk 4 from litter samples and at
wk 7 from poultry feed. Densities of C. albicans remained very high in litter
samples (63.2 cfu/g) even after new litter was added at wk 10. To analyze the
genetic polymorphism of A. fumigatus, the most pathogenic mold in birds, a total
number of 198 isolates (134 from air, 34 from litter, and 30 from feed samples)
were genotyped using 2 polymorphic microsatellite markers. More than half (42 out
of 73, 57.5%) of the genotypes were detected only once. This finding suggests
that the contamination of the breeding environment is not due to a single source
and confirms the very high genetic diversity of environmental A. fumigatus
isolates. As during the study period, no outbreak of fungal infections occurred;
the levels of fungal contaminations reported here do not seem sufficient, at
least alone, to trigger fungal infections.
PMID- 17032817
TI - Effects of travel distance and the season of the year on death rates of broilers
transported to poultry processing plants.
AB - Death losses among broilers transported to processing plants are caused by poor
welfare. The number of birds dying during transport and in processing plants
shortly after arrival there may serve as an indicator of the quality of welfare
during loading and transport. In the Czech Republic, shipments of broilers to
processing plants were monitored from 1997 to 2004. It was found that the
mortality of broilers during transport was 0.247%, but it varied according to the
transport distance to the processing plant from 0.146% (50 km maximum) to 0.862%
(>300 km). The broiler mortality in transit was also influenced by the season of
the year. The highest mortality was found in summer months, especially in June,
July, and August, and in winter months, especially in December, January, and
February. A comparison between period 1 (1997 to 2000) and period 2 (2001 to
2004) showed a long-term adverse trend in the number of broilers dying during
transport to processing plants for all of the distances monitored (except
transport distances <50 km), because the overall number of dead birds on arrival
to processing plants increased from 0.224 to 0.265% (index of 1.18). This
difference is statistically significant (P = 0.000). The stress caused to
broilers by transport to processing plants is reflected in higher transport
related mortality of the birds. Long-term trends point to an increase in death
losses of broilers. Longer transport distances and transportation in summer and
winter months have led to an increase in death losses among broilers transported
to processing plants.
PMID- 17032818
TI - Lack of estrogenic or antiestrogenic actions of soy isoflavones in an avian
model: the Japanese quail.
AB - Isoflavones are soy compounds that possess weak estrogenic and antiestrogenic
activities. In addition, phytochemicals, including isoflavones, may play a role
in regulating seasonal reproductive cycles. As soy is a common constituent in
poultry diets, the effect of these compounds on the reproductive system of
production birds may be of concern. The present study examined the putative
effects of soy isoflavones supplemented into the diet at 1 and 5% using endpoints
of growth and reproduction in the Japanese quail. Isoflavones did not exert an
effect on growth, feed intake, growth:feed, or the weight of the estrogen
sensitive immature oviduct in female quail. Furthermore, isoflavones did not
influence the growth of the oviduct stimulated by exogenous estradiol. Similarly,
isoflavones did not influence growth, feed intake, or growth:feed in male quail.
However, isoflavones at 1%, but not 5%, in the diet reduced photoperiod-induced
testis development 40% vs. control. In contrast, isoflavones did not influence
testis regression stimulated by exogenous estradiol in sexually maturing male
quail. The present results suggest that isoflavones may exert modest endocrine
disruptor-like effects on reproduction in male, but not female, quail.
PMID- 17032819
TI - Tissue expression and association with fatness traits of liver fatty acid-binding
protein gene in chicken.
AB - Fatty acid-binding proteins belong to a superfamily of lipid-binding proteins
that exhibit a high affinity for long-chain fatty acids and appear to function in
metabolism and intracellular transportation of lipids. The current study was
designed to investigate expression characterization and association with growth
and composition traits of the liver fatty acid-binding protein (L-FABP) gene in
the chicken. Northern blot analysis indicated that the gene, similar to the
mammal L-FABP gene, was expressed only in liver and intestinal tissues. The mRNA
levels of the chicken L-FABP gene in liver and intestine had significant
differences between the broilers and Baier layers. The China Agricultural
University F(2) population was used in the present study. Body weight and body
composition traits were measured in the populations. Primers for the coding
region and 5' upstream region of the L-FABP gene were designed according to
chicken genomic and cDNA sequence. Polymorphisms were detected by DNA sequencing,
and the PCR single-strand conformation polymorphisms method was developed to
genotype the F(2) population. The results indicated that the L-FABP gene
polymorphisms were associated with abdominal fat weight and percentage of
abdominal fat, and the L-FABP gene could be a candidate locus or linked to a
major gene(s) that affects fatness traits in the chicken. The results of the
current study provided basic molecular information for studying the role of the L
FABP gene in the regulation of lipid metabolism in avian species.
PMID- 17032820
TI - A potential molecular marker for selection against abdominal fatness in chickens.
AB - The peroxisome proliferators-activated receptor-gamma coactivator-1alpha (PGC
1alpha) was investigated as a candidate gene for growth and fatness traits in
chicken because of its prominent role in muscle fiber specialization and
adipogenesis. A single nucleotide polymorphism (SNP) from G to A at position 646
of the open reading frame of chicken PGC-1alpha gene causing an Asp216Asn amino
acid substitution was identified. The frequencies of alleles and genotypes were
significantly different among 6 chicken breeds (P < 0.01). The White Plymouth
Rock had the highest frequency (0.67) of allele G, whereas the White Leghorn had
the lowest (0.18). The associations of the SNP with the growth and fatness traits
were evaluated in 332 F(2) birds from an experimental cross of White Plymouth
Rock x Silkies. No association was found between the SNP and growth-related
traits. However, abdominal fat weight at 12 wk of age for birds with genotype GG
was 34.26 and 28.71% higher than those with genotypes AA and AG, respectively (P
< 0.01), indicating that the Asp216Asn polymorphism of the PGC-1alpha gene could
be used as a novel potential molecular marker for selection against abdominal
fatness without interfering in regular breeding for growth rate of chickens.
PMID- 17032821
TI - Upregulation of oxidative burst and degranulation in chicken heterophils
stimulated with probiotic bacteria.
AB - The immune system of neonatal chicks is functionally immature during the first
week of life. Researchers have previously demonstrated that the avian humoral
response can be increased with probiotics. Although the humoral response provides
the chick with an effective mechanism to combat pathogens, sufficient antibody
titers are not attained until 7 to 10 d postinfection. However, the innate immune
system (i.e., heterophils) can respond much more quickly to pathogens. The
objective of this study was to determine whether probiotic bacteria can also
upregulate heterophil function. Heterophils were isolated from the peripheral
blood of neonatal chickens by using a discontinuous density gradient. Oxidative
burst and degranulation are bactericidal mechanisms used by heterophils to kill
pathogens and were used in this study as indicators of heterophil function. We
found that each of the 10 "generally recognized as safe" probiotic isolates
(designated G1 to G11) tested in vitro were capable of increasing (P < 0.05)
heterophil oxidative burst and degranulation when compared with unstimulated
controls. Bacillus subtilis (G3), Lactococcus lactis lactis (G6), and
Lactobacillus acidophilus (G8) isolates were determined to elicit the greatest
heterophil response in vitro and were subsequently fed to chicks. Phosphate
buffered saline or 1 of these 3 probiotic isolates (approximately 2.5 x 10(8)
cfu/chick; 50 chicks/treatment) resuspended in PBS was administered by oral
gavage on the day of hatch. Heterophils were isolated from chicks from each of
these 4 treatment groups 24 h posttreatment. Significant increases in heterophil
degranulation and oxidative burst were observed with the G3-, G6-, and G8-treated
chicks when compared with heterophils isolated from birds with no probiotic
treatment. These data suggest that probiotic bacteria can significantly improve
heterophil oxidative burst and degranulation in broilers. To our knowledge, this
is the first study demonstrating a relationship between probiotics and avian
heterophil function.
PMID- 17032822
TI - Cytokine expression in chicken peripheral blood mononuclear cells after in vitro
exposure to Salmonella enterica serovar Enteritidis.
AB - Cytokines are secreted proteins involved with cell recruitment and regulation of
both innate and adaptive immune responses. They are essential for an effective
host immune response to pathogens. The objective of this study was to determine
the effect of Salmonella enterica serovar Enteritidis (S. Enteritidis) exposure
and genetic line on cytokine mRNA expression level of cultured chicken peripheral
blood mononuclear cells (PBMC). Interleukin-2, interleukin-6 (IL-6), CXCLi2, and
transforming growth factor-beta4 (TGF-B4) messenger ribonucleic acid expression
was measured by quantitative reverse transcription-PCR assays in PBMC from 3
chicken lines (broiler, Leghorn, Fayoumi) after in vitro exposure to S.
Enteritidis. The PBMC were isolated from uninfected birds and cultured overnight.
The next day, live pathogenic S. Enteritidis was added to half of the cultures.
All cultures were harvested after 2 or 4 h of exposure. Exposure to S.
Enteritidis downregulated IL-6, CXCLi2, and TGF-beta4 but not interleukin-2 mRNA
expression. No significant genetic line or exposure time effects were detected.
These findings demonstrate that exposure of chicken PBMC to S. Enteritidis can
induce a rapid change in both proinflammatory (IL-6, CXCLi2) and antiinflammatory
(TGF-beta4) cytokine gene expression.
PMID- 17032823
TI - Effects of cysteamine on growth performance, digestive enzyme activities, and
metabolic hormones in broilers.
AB - A total of 600 avian male broilers at the age of 1 d were used to investigate the
effects of cysteamine (CSH) on growth performance, digestive enzyme activities,
and concentrations of serum hormones. The broilers received the same basal diets,
with CSH added at 0 (control), 60, 90, 120, or 150 mg/kg. The feeding program
consisted of a starter diet until 21 d and a grower diet until 42 d. The broilers
with addition of CSH at 60 or 90 mg/kg had significantly higher growth rates
during d 1 to 21 or d 21 to 42 compared with the control, respectively. However,
adding 150 mg of CSH/kg significantly suppressed the growth of broilers. Adding
60 mg of CSH/kg significantly increased the activities of protease, amylase, and
lipase in the pancreas and small intestinal contents during d 1 to 21, and the
activities of protease and amylase in the small intestinal contents during d 21
to 42. Adding 90 mg of CSH/kg significantly increased the activities of lipase
during d 1 to 21 and protease, amylase, and lipase during d 21 to 42 in small
intestines. The activities of digestive enzymes during the whole period were
suppressed by adding 150 mg of CSH/kg. The concentration of serum thyroxine was
higher in the CSH-added birds during the whole period, whereas serum
triiodothyronine was higher only during d 1 to 21 compared with the control.
These findings indicate that low doses of dietary CSH may improve the growth
performance and the activities of the digestive enzyme, but high doses of CSH
appear to be detrimental to growth and digestion.
PMID- 17032824
TI - Relationship between bicarbonate retention and bone characteristics in broiler
chickens.
AB - Determination of the bicarbonate retention factor (BRF) is an important step
during development of the indicator amino acid oxidation technique for use in a
new model. A series of 4-h oxidation experiments were performed to determine the
BRF of broilers aged 7, 14, 21, 28, 35, and 42 d using 4 birds per age group. A
priming dose of 1.2 microCi of NaH(14)CO(3), followed by eight half-hourly doses
of 1 microCi of NaH(14)CO(3) were given orally to each of 4 birds per age. The
percentage of (14)C dose expired by the bird at a steady state was measured.
These birds, as well as 12 additional birds matched for age and BW, were killed,
and femur bone mineral density was measured by quantitative computed tomography
to determine the relationship between bone development and bicarbonate retention
at each age. There was a correlation (r = 0.50; P < 0.05) between total cross
sectional femur bone mineral density and bicarbonate retention at each age. A
prediction equation (Y = 6.95 x 10(-2)X - 3.51 x 10(-5)X(2) + 27.58; P < 0.0001,
R(2) = 0.79) where Y = bicarbonate retention and X = BW was generated to predict
Y as a function of X. Bicarbonate retention values peaked at 28 d, during the
stage of the most rapid bone deposition and the highest growth rate. A constant
BRF was found from 1,900 to 2,700 g of BW of 35.15 +/- 1.095% (mean +/- SEM).
This retention factor will allow the accurate correction of oxidation of (14)C
labeled substrates in broilers of different ages and BW in future indicator amino
acid oxidation studies.
PMID- 17032825
TI - Response of broilers to feeding low-calcium and phosphorus diets plus phytase
under different environmental conditions: body weight and tibiotarsus
mineralization.
AB - Three experiments on Ross broiler chickens were conducted in 3 locations: cages
(Experiment 1), floor pens (Experiment 2), and commercial farms (Experiment 3).
The effect of low-total P (TP) wheat-soybean based diets plus microbial phytase
(Natuphos) was evaluated. Four experimental starter and finisher diets were used
in a 2-phase feeding program, as follows: control diet (SC until 21 d, FC from 22
to 42 d); 2 diets (SL400 and SL600 until 21 d, FL400 and FL600 from 22 to 42 d)
with low TP (0.61% for starter and 0.54% for finisher), including 400 and 600
U/kg of phytase, respectively; and a very low-TP (0.52% for starter and 0.44% for
finisher) diet (SVL600 until 21 d, FVL600 from 22 to 42 d) with 600 U/kg of
phytase. In Experiment 1 (broilers in cages had movement limitation and no access
to litter), no differences in BW, tibiotarsus mineralization, or mineral
metabolism were observed among diets. In Experiment 2 (broilers in floor pens had
movement limitation and access to litter), at 21 d of age, the lowest tibiotarsus
ash percentage and BW were shown by birds fed the SVL600 diet. At 42 d of age,
broilers fed the FC diet were the lightest. For the rest of the parameters of
tibiotarsus mineralization and mineral metabolism measured in Experiment 2, no
differences were shown. In Experiment 3 (broilers in commercial farms had access
to litter without movement limitation), the BW of broilers fed the SC diet was
the highest at 21 d of age. At 42 d of age, the broilers fed FL400 and FL600
diets were the heaviest. At the end of Experiment 3, broilers fed the FC diet had
the highest dry litter Ca and P, whereas broilers fed the FVL600 diet had the
lowest values. In conclusion, the very low-TP wheat-soybean based diet
supplemented with 600 U/kg of phytase was sufficient to optimize all the
parameters measured in Experiment 1 but not in Experiments 2 and 3. Therefore,
when evaluating Ca and P in phytase-supplemented diets for broilers, it is
necessary to bear in mind the environmental conditions of experimentation.
PMID- 17032826
TI - Conversion of the methionine hydroxy analogue DL-2-hydroxy-(4-methylthio)
butanoic acid to sulfur-containing amino acids in the chicken small intestine.
AB - dl-Methionine or its corresponding hydroxy analogue, DL-2-hydroxy-(4-methylthio)
butanoic acid (DLHMB), are commonly added to commercial animal diets to satisfy
the TSAA requirement. The utilization of DLHMB as a supplementary source of Met
begins with its conversion to L-Met via a 2-step mediated process. L-Methionine
can then be transsulfurated to L-Cys, which, in turn, can be catabolized to
taurine (TAU). In the present study, the capacity of the chicken small intestine
to convert DLHMB to L-Met and to use this amino acid as a source for L-Cys and
TAU production was evaluated. The appearance of Met in the serosal compartment of
everted sacs incubated with DLHMB is higher in the presence of an H(+) gradient
(mucosal pH 5.5 vs. 7.4). Serosal Cys and TAU concentration was compared in
everted sacs incubated at a mucosal pH of 5.5 with DLHMB or L-Met, and the
results show significantly higher values after incubation with the hydroxy
analogue. Regional comparisons indicate no significant differences in the
appearance of serosal Met and Cys, although lower values were obtained for TAU in
the duodenum than in the jejunum and ileum. The profile of non-S amino acids was
also determined and revealed no significant differences between DLHMB- and L-Met
incubated sacs. In conclusion, Cys and TAU content in chicken enterocytes is
higher when DLHMB is used as a Met source.
PMID- 17032827
TI - The effect of feeding calcium- and phosphorus-deficient diets to broiler chickens
during the starting and growing-finishing phases on carcass quality.
AB - There is considerable data on the effect of reducing inorganic Ca and P in
broiler finisher diets on carcass quality. However, there is limited information
on the effect of reducing dietary Ca and P during the different phases of
growout. Two experiments were conducted from 0 to 35 d in floor pens. In both
experiments, at least 4 replicates per treatment (50 chicks per replicate) were
used. Corn-soybean meal and soybean oil-based diets deficient in Ca and P were
fed. During the starter phase (ST), from 0 to 18 d, chicks were fed a 23% CP diet
containing 0.60% Ca and 0.47% total P (tP). During the grower-finisher phase
(GF), from 19 to 35 d, birds were fed a 19% CP diet containing 0.30% Ca and 0.37%
tP. A combination of 1,000 phytase units/kg of Natuphos phytase and 5 microg/kg
of 1alpha-hydroxycholecalciferol (P + 1alpha) was supplemented to some of the
feed during the ST and GF. Diets containing adequate Ca and P were also fed
during the ST (0.90% Ca and 0.68% tP) and GF (0.80% Ca and 0.67% tP). The level
of tibia ash and the incidence of bone disease were measured at 18 and 35 d. At
the end of the experiments, birds were processed and evaluated for muscle
hemorrhages and broken bones. In both experiments, broilers fed diets that were
not P + 1alpha supplemented demonstrated poor bone mineralization, considerable
leg problems, and a high incidence of broken bones after processing. Broilers fed
P + 1alpha throughout had more broken clavicles and femurs compared with birds
fed the adequate diets. Day-18 tibia ash was significantly correlated to broken
tibias and femurs during processing. Day-35 tibia ash was better correlated to
bloody breast meat than to broken bones. It is concluded that carcass quality
depends on the levels of Ca and P fed and the age of the bird. Tibia ash,
traditionally used as an indication of bone strength, was better correlated to
the incidence of bloody breasts.
PMID- 17032828
TI - Effect of manganese source on manganese absorption by the intestine of broilers.
AB - Two experiments were conducted to investigate the effect of Mn source on Mn
absorption by the intestine of broilers. In Experiment 1, the effect of Mn
source, including MnSO(4), 2 Mn-amino acid chelates (Mn-Gly and Mn-Met)
synthesized in our laboratory, 3 Mn-amino acid complexes with different complex
strengths (Mn-Met E, Mn-AA A, and Mn-AA B), and 2 mixtures of MnSO(4) with Gly or
Met, on Mn absorption was assessed with ligated loops of different small
intestinal segments of broilers. In Experiment 2, the absorption of Mn from
MnSO(4), Mn-AA A, and Mn-AA B was compared with intact broilers fed ad libitum.
The criterion used for comparison was the Mn content of hepatic portal vein
plasma. The absorption of Mn was higher (P < 0.0002) by ligated ileal loops than
by duodenal and jejunal ones. Met supplementation increased (P < 0.03) the
absorption of Mn as MnSO(4). The absorption of Mn as Mn-AA A and Mn-AA B with
moderate and strong complex strengths, respectively, were higher (P < 0.05) than
those of Mn as MnSO(4) and Mn-Met E with weak complex strength. On d 7 and 9 of
Experiment 2, the Mn content of portal vein plasma was higher (P < 0.03) for Mn
AA B with strong complex strength than for MnSO(4). On d 9, Mn content in plasma
was higher (P < 0.01) for Mn-AA B with strong complex strength than for Mn-AA A
with a moderate one. The results from this study confirm that the ileum was the
main site of Mn absorption for broilers, and Met was more effective in
facilitating Mn absorption than Gly as a ligand. Organic Mn was more efficiently
absorbed than inorganic Mn (MnSO(4)); the absorption of organic Mn with moderate
and strong complex strengths was greater than that of the organic Mn, which was
weak, and the absorption of organic Mn with strong complex strength was greater
than that of the organic Mn with a moderate strength.
PMID- 17032829
TI - Comparison of amino acid digestibility in broiler chickens, turkeys, and Pekin
ducks.
AB - The objective of this study was to compare prececal amino acid (AA)
digestibilities in broilers, turkeys, and Pekin ducks that were 3 wk old. Five
diets were used: a basal diet and diets that contained either soybean meal (SBM)
or rapeseed meal (RSM) at the expense of starch each at either 150 or 300 g/kg.
The differences in dietary CP and AA concentrations resulted only from the
inclusion of SBM or RSM. Titanium dioxide was used as an indigestible marker.
Each diet was allocated to 6 pens of 12 birds from each species and provided ad
libitum for 1 wk starting at 14 d of age. Digesta were sampled on a pen basis
from the distal two-thirds of the section between Meckel's diverticulum and 2 cm
anterior to the ileocecocolonic junction. Ingested and digested amounts of AA
were determined for each pen. Digestibilities for the 2 meals were then
determined by a multiple linear regression analysis, which makes a correction for
basal endogenous AA losses unnecessary. Digestibilities for essential AA from the
meals varied between 92% (Met, RSM, broilers) and 62% (Val, RSM, ducks).
Digestibilities were not significantly different between SBM and RSM for broilers
and turkeys, but the average digestibility across all AA was slightly higher for
SBM and lower for RSM in turkeys than in broilers. Digestibilities were lower in
ducks than in the 2 other species, and significant differences between SBM and
RSM were detected for some AA in ducks. Amino acid digestibility ranking was very
similar between broilers and turkeys but different for the 2 meals. It was
concluded that differences among species cannot be explained by differences in
basal endogenous AA losses among species. Amino acid digestibilities determined
with broilers should not be used in formulating feed for ducks.
PMID- 17032830
TI - Modeling of threonine requirement in fast-growing chickens, depending on age,
sex, protein deposition, and dietary threonine efficiency.
AB - In addition to dose-response studies, modeling of N utilization, depending on
intake of the first limiting amino acid in the diet, is one of the tools for
assessing amino acid requirements in growing animals. Based on a verified
nonlinear N-utilization model and following the principles of the diet dilution
technique, N-balance experiments were conducted to estimate the Thr requirement
of fast-growing chickens (genotype Cobb), depending on age, sex, CP deposition.
and efficiency of dietary Thr utilization. Different predictions were made for
the feed intake to conclude the optimal Thr concentration in the feed. The
results are based on N-balance experiments with a total of 144 male and 144
female growing chickens within 4 age periods (I: 10 to 25 d; II: 30 to 45 d; III:
50 to 65 d; IV: 70 to 85 d), using diets with graded protein supply (6.6, 13,
19.6, 25.1, 31.8, and 37.6% CP in DM) from high-protein soybean meal with a
constant amino acid ratio and Thr as the first limiting amino acid (3.87 g of
Thr/100 g of CP; dietary Lys:Thr = 1:0.54). The observed optimal Thr
concentration (% of feed) was influenced by age, sex, level of CP deposition,
dietary efficiency of Thr utilization, and predicted feed intake. For male
chickens, assuming an average CP deposition (60% of the potential) and average
efficiency of Thr utilization, 0.78% (10 to 25 d), 0.73% (30 to 45 d), 0.65% (50
to 65 d), and 0.55% (70 to 85 d) total dietary Thr were observed as optimal total
Thr concentration in the diet (corresponding to 60, 135, 160, and 180 g of daily
feed intake, respectively). Data are discussed in context with the main factors
of influence like age, sex, level of daily CP deposition, efficiency of dietary
Thr utilization, and predicted feed intake.
PMID- 17032831
TI - Spontaneously occurring fibroid tumors of the laying hen oviduct.
AB - Spontaneously occurring benign uterine leiomyomas (fibroids) are the most common
tumors of reproductive-age women. It is estimated that more than 70% of all women
will develop uterine fibroids, and the presence of these tumors is a primary
cause of hysterectomies. Research into the causes and treatment of uterine
fibroids is hampered by a lack of reliable animal models for the disease.
Leiomyomas that appear to be outwardly similar to human uterine fibroid tumors
are known to occur on the oviducts of laying hens over 2 yr of age. The objective
of this study was to characterize these tumors and compare them to human uterine
fibroids to determine the suitability of the aging hen as a model system for the
study of the disease. In this study, hens at 5 yr of age were examined for the
presence of oviduct-associated fibroid tumors. Tumors were found attached to the
internal surface of the oviduct, embedded in the oviduct wall, or attached to the
exterior of the magnum and isthmus. Tumor and normal oviduct samples were frozen
or fixed in formalin for histological analyses or immunohistochemistry for
estrogen and progesterone receptors, proliferating cell nuclear antigen and Bcl-2
protein expression. Human uterine fibroid samples were acquired and evaluated
compared with hen oviduct fibroids. The results indicate that laying hen fibroid
tumors are similar to human fibroid tumors with respect to estrogen and
progesterone receptors, localized cellular proliferation, and expression of the
Bcl-2 protein.
PMID- 17032832
TI - Effects of caponization and different exogenous androgen on the bone
characteristics of male chickens.
AB - The effects of caponization and androgen implantation on the bone characteristics
of male chickens were evaluated. Healthy Single Comb White Leghorn cockerels were
caponized or sham operated (sham) at 12 wk old. Sixteen birds from each group
were selected for a 14-wk experiment in trial 1. Sixteen birds from the sham
group and 64 from the caponized group (randomly allocated into 4 treatments) were
implanted with 10.4 +/- 0.4 mg (1.62-mm i.d., 3.6-mm o.d.) of cholesterol,
testosterone (TES), 5alpha-dihydrotestosterone (5alpha-DHT), or 19
nortestosterone (19-NorT) and were assigned to trial 2 for a 14-wk experiment.
The results from trial 1 showed that caponization increased BW (P < 0.05) and
decreased tibia stress, ash content, and P content with higher blood P
concentration (P < 0.05) as compared with the sham group. In trial 2, the
cholesterol implantation group showed the lowest tibia breaking strength, bending
moment, stress, and ash content (P < 0.05). The 19-NorT implantation group showed
decreased (P < 0.05) blood Ca and P concentration but increased tibia ash and P
content, reaching the same level as the sham group (P > 0.05). The adverse
effects of caponization on bone characteristics could be improved using androgen
implantation. Among the implantation groups, the 19-NorT implantation group
showed the best improvement in tibia breaking strength and bending moment,
followed by the TES and 5alpha-DHT groups. The TES group showed the best
improvement in tibia stress, followed by the 19-NorT and 5alpha-DHT groups.
PMID- 17032833
TI - Adaptation of epithelial sodium-dependent phosphate transport in jejunum and
kidney of hens to variations in dietary phosphorus intake.
AB - The objective of this study was to explore the homeostatic response of jejunal
and renal epithelia regarding the inorganic phosphate (P(i)) transport capacities
to variations in dietary total phosphorus (tP) supply in hens. Adaptive processes
were determined by quantitative measures of intake and excretion, P(i) transport
studies across brush border membranes, and semiquantitative detection of sodium
dependent phosphate transporters (NaPi II) based on mRNA expression in the
jejunum and kidney. Twelve hens (4/group) were adapted to 3 tP feeding levels in
a pair-fed manner (60 g/d): low P diet with 0.073% tP, medium P diet with 0.204%
tP, and high P diet with 0.343% tP. Excretion was measured during the last 5 d of
a 16-d feeding period. After slaughtering, jejunal mucosa and renal cortex were
removed. Tissues were used for (32)P uptake studies in brush-border membrane
vesicles by rapid filtration technique and NaPi II mRNA expression studies by
northern analyses. Plasma P(i) concentrations were additionally measured. The
NaPi II transporter mRNA could specifically be detected in chicken jejunum and
kidney. Functional parameters of Na(+)-dependent P(i) transport indicated that
these transporters were involved in chicken P(i) transport across the apical
membranes of jejunal and renal epithelia. Increased tP intake resulted in an
increased overall tP excretion. Correlating individual data from all animals by
linear regression highlighted that the adaptive decrease of renal P(i) transport
capacity and NaPi IIa mRNA expression was associated with an increase in plasma
P(i) levels and resulted in a higher tP excretion. Jejunal P(i) transport
capacity and NaPi IIb mRNA expression did not react to variations in dietary tP
supply. In conclusion, the homeostatic response was mainly based on the adaptive
capacity of the kidney in hens.
PMID- 17032834
TI - Age-related changes in the distribution of lean fat with skin and bones in goose
carcasses.
AB - The experimental materials comprised White Italian geese (128 males and 128
females) reared to 14 wk of age. The birds were fed standard diets ad libitum.
Starting from 2 wk of age, 14 males and 14 females were killed at 2-wk intervals.
The carcasses were divided into neck, wings, legs, breast, and back, which were
then dissected into muscle, skin with fat, and bones. Before slaughter, the BW of
males and females were 6,814 and 5,736 g, respectively. At 2 wk of age, more than
half of total muscle content was in the legs (60.98%), and the rest was in the
back (17.84%), neck (9.43%), breast (8.78%), and wings (2.97%). To 10 wk of age,
the rate of muscle deposition was relatively slow in the legs (a decrease to
31.29%) and fast in the breast and wings (an increase to 34.12 and 12.90%,
respectively). Age-related changes in the distribution of skin with fat in the
carcass were smaller, compared with changes in muscle distribution. A rising
tendency was observed in the muscle content of wings and breast and in the
content of skin with fat in the wings and neck, whereas a falling tendency was
observed in the other carcass parts. Over the first 8 wk, the proportion of bones
decreased in the legs, back, and neck and increased in the wings and breast, as
compared with the total bone weight in the carcass.
PMID- 17032835
TI - Incidence of pectoralis major turkey muscles with light and dark color in a
Portuguese slaughterhouse.
AB - Turkey meat and processed products are very popular in Portugal. However, no
studies have been made to assess turkey meat quality. The main objective of this
study was to evaluate the quality of turkey breast meat in a Portuguese
slaughterhouse, differentiating it to obtain better industrial management,
performance, and consumer contentment. Nine hundred and seventy-seven male
turkeys (from 16 to 20 wk old) from different flocks (BUT 9 and BIG 6) were
evaluated to assess meat quality. Turkeys were slaughtered on different days,
electrically stunned (225 V/3 s), and scalded in a vertical water bath at 81
degrees C/5 min. On the slaughter line, the pH and temperature were measured on
the pectoralis muscle 15 min postmortem. The carcasses were fast-cooled in a
tunnel (-2 degrees C/2 m.s(-1)/90% RH) for 2 h and kept in a refrigeration
chamber (0 degree C/85% RH) until deboning (approximately 24 h postmortem). Color
and pH 24 h postmortem (pH(24)) were measured on the pectoralis major muscle
after carcass deboning. Pectoralis major muscles were selected according to
criteria used by Barbut (1996) and drip loss, cooking loss, and total pigments
analysis were performed on 67 different sliced meat samples. Muscles classified
by pH decline rate, called rapid glycolytic, did not present final quality
characteristics that could relate them with pale, soft, and exudative- (PSE) like
meat, because there was no relationship between pH 15 h postmortem and lightness
(L*), drip loss, or cooking loss. The differences, founded on physicochemical
characteristics within pectoralis major muscles, allowed us to establish a
criteria of turkey meat quality for dark and PSE-like meat, with L* < or = 44 and
pH(24) > or = 5.8 and L* > or = 50 and pH(24) < 5.8, respectively. Based on
criteria, the studied population presented 8.1% of carcasses with PSE-like
muscles and 12.1% with dark muscles. The association of pH(24) and L* as criteria
classification can be useful to classify turkey meat quality.
PMID- 17032836
TI - Microcracks in eggs.
AB - An experimental program of mechanical testing has shown that microcracks initiate
in hens' eggs at loads less than that necessary to cause total structural
failure. In contact loading, computational modeling and numerical analysis show
that very high stress levels develop on the inner surface of the eggshell as it
conforms to a hard contact surface. This causes a series of microcracks to
initiate at the inner surface of the shell and radiate out from the load site. A
series of concentric circumferential microcracks also develop beneath the cuticle
from the edge of the contact zone. Calculations relating to the eggshells'
dynamic response indicate that microcracks have a little effect on the structural
stiffness and resonant frequencies of the egg. As a result, microcracks are
unlikely to be detected by online crack detection systems, which rely on
mechanical excitation. Eggs in retail outlets are likely to contain microcracks
as a result of insults experienced during the collection, grading, and packing
processes. Because the eggshell forms the first line of defense against
potentially pathogenic microorganisms entering the egg contents, microcracks
could potentially compromise egg safety.
PMID- 17032837
TI - Effect of oral administration of bismuth compounds on Campylobacter colonization
in broilers.
AB - Bismuth compounds have been used since the 18th century to treat gastrointestinal
ailments in man. Colloidal bismuth subcitrate (De-Nol) is currently used in
combination with antibiotics to reduce enteric Helicobacter pylori colonization
as a treatment of stomach ulcers. We investigated whether bismuth citrate or its
parent compound, colloidal bismuth subcitrate, would reduce colonization of the
closely related foodborne pathogen, Campylobacter jejuni in chickens. In 2
studies, birds were either fed 0, 50, or 200 ppm bismuth citrate or bismuth
subcitrate (De-Nol) for 10 or 21 d and were orally challenged with 7 combined
strains of C. jejuni (n = 6 birds/treatment). For both treatment groups, cecal
Campylobacter colonization was reduced when birds were fed 200 ppm for 10 d but
not 21 d. For the 50 ppm treatment group, only birds dosed with bismuth citrate
for 21 d demonstrated any reduction in cecal Campylobacter concentrations when
compared with controls. These data suggest that bismuth citrate and colloidal
bismuth subcitrate may reduce cecal colonization by Campylobacter in broilers,
but these effects are inconsistent.
PMID- 17032838
TI - Effects of S6-strain Mycoplasma gallisepticum inoculation at ten, twenty-two, or
forty-five weeks of age on the blood characteristics of commercial egg-laying
hens.
AB - In 2 consecutive trials of the current study, the effect of the age of
application of S6-strain Mycoplasma gallisepticum (S6MG) inoculation on the blood
characteristics of commercial layers housed and maintained under controlled
conditions was determined. The ages of inoculation compared were those before lay
at 10 wk of age, during onset of lay at 22 wk of age, and during postpeak lay at
45 wk of age. In each trial, hematocrit, plasma protein, and serum cholesterol,
triglycerides, and Ca were determined at 20, 24, 32, 43, 47, and 58 wk of age.
The data from both trials were pooled then analyzed together, whereas, data from
wk 20 (effect of 10-wk S6MG inoculation); data from wk 24, 32, and 43 (effects of
10- and 22-wk S6MG inoculations); and data from wk 47 and 58 (effects of 10-, 22
, and 45-wk S6MG inoculations) were analyzed separately. At wk 20, hematocrit was
higher in birds inoculated with S6MG at 10 wk compared with sham-inoculated
birds, and across wk 24, 32, and 43, serum Ca was higher in birds inoculated with
S6MG at 10 or 22 wk compared with those that were sham-inoculated. Serum Ca level
across wk 47 and 58 was higher in birds inoculated with S6MG at 10 wk compared
with sham-inoculated controls and birds inoculated with S6MG at 22 wk, with 45-wk
S6MG-inoculated birds being intermediate. The response of serum cholesterol level
at 47 wk to S6MG inoculation at either 10, 22, or 45 wk compared with controls
was nearly opposite to that of the response observed at 58 wk. However, serum
triglycerides were depressed only at wk 47 due to the 45-wk S6MG inoculation
compared with all other treatments. Variable post-peak alterations in serum Ca
and lipids occur in response to the timing of S6MG inoculation in layers housed
under controlled conditions.
PMID- 17032839
TI - Consumers' preferences toward techniques for improving manual catching of
poultry.
AB - Growing interest in ameliorating animal welfare has prompted numerous studies
that compare various aspects of manual and mechanical catching. In general,
mechanical catching has been adopted as a realistic alternative for manual
catching. The success of a catching machine as an alternative for manual catching
does not only depend on its practical applicability, but also on its acceptance
by "the general public." In the history of technological change, public
perception of new technologies has often been ambivalent. Against this
background, it is important to know how consumers perceive the production
methods. This paper provides an evaluation of the preferences for catching
methods by "society" to investigate whether there is a shift in preference due to
the confrontation with video segments and the potential effect of awareness and
importance attached to animal welfare on preference. Data were gathered through a
questionnaire-based survey, including 450 respondents, performed in Belgium. For
this study, the data indicated that when subjects were provided information
concerning catching methods of broilers, they liked the technology much more.
However, for those respondents without prior awareness of both catching methods
or with high importance attached to animal welfare, giving information could not
convince them of the advantage of using a mechanical catching machine. It is
obvious that preference varies with the awareness and experience of the
respondents. Future research should move forward from simple assessments of
consumer concerns about the technologies and focus more directly on questions and
issues related to the consumer's expected bottlenecks of these technologies. In
this way, working at a better understanding can directly influence the acceptance
of these technologies.
PMID- 17032840
TI - Fine-mapping of coccidia-resistant quantitative trait loci in chickens.
AB - Two commercial, pure broiler lines with different susceptibility to coccidiosis
were used to fine-map QTL associated with the previously identified marker
LEI0101, located at 259 cM on chromosome 1 and shown to be significantly
associated with disease resistance. Eight additional microsatellite markers
linked to LEI0101 were used for genotyping of F(1) parents and F(2) offspring (n
= 314), and their associations with oocyst shedding, as a marker of disease
resistance, were determined in birds experimentally infected with Eimeria maxima.
Single-point analysis of 4 families showed that logarithm of odds (LOD) scores at
all marker loci were > 0.5, with the exception of marker LEI0071, located at 242
cM (LOD score = 2.45). Multipoint analysis showed a maximum LOD score between
LEI0071 and LEI0101 at 254 cM (LOD score = 3.74). Although the LEI0071 marker was
mapped near LEI0101 by linkage analysis, the physical location of LEI0071 was not
identified. Further studies to determine the physical locations of these and
other markers will allow additional application association mapping techniques
using single nucleotide polymorphism markers.
PMID- 17032841
TI - Molecular cloning, genomic organization, and expression of three chicken 5'-AMP
activated protein kinase gamma subunit genes.
AB - The 5'-AMP-activated protein kinase (AMPK) plays a key role in regulating
cellular energy homeostasis. The AMPK is a heterotrimeric enzyme complex that
consists of 1 catalytic (alpha) and 2 regulatory (beta and gamma) subunits.
Mutations of the gamma subunit genes are known to affect AMPK functioning. In
this study, we characterized the genomic organization and expression of 3 chicken
AMPK gamma subunit genes (cPRKAG). Alternative splicing of the second exon of the
cPRKAG1 gene resulted in 2 transcript variants that code for predicted proteins
of 298 and 276 amino acids. Use of an alternate promoter and alternative splicing
of the cPRKAG2 gene resulted in 4 transcript variants that code for predicted
proteins of 567, 452, 328, and 158 amino acids. Alternative splicing of exon 3 of
the cPRKAG3 gene resulted in the production of "long" and "short" transcript
variants that code for predicted proteins of 382 and 378 amino acids,
respectively. We found evidence for differential expression of individual gamma
subunit gene transcript variants and, in some cases, tissue-specific expression
was observed. The cPRKAG subunit genes displayed similar structural features and
high sequence homology compared with corresponding mammalian gamma subunit gene
homologues.
PMID- 17032842
TI - The three and one-half year radiology residency.
PMID- 17032843
TI - Dural tail: another face of facial nerve schwannoma?
PMID- 17032844
TI - A case meeting clinical brain death criteria with residual cerebral perfusion.
PMID- 17032845
TI - Radiation worker mortality: intersociety call for survey participation.
PMID- 17032846
TI - Magnetic resonance imaging of the fetal brain and spine: an increasingly
important tool in prenatal diagnosis: part 2.
AB - Fetal MR imaging is an increasingly available technique used to evaluate the
fetal brain and spine. This is made possible by recent advances in technology,
such as rapid pulse sequences, parallel imaging, and advances in coil design.
This provides a unique opportunity to evaluate processes that cannot be
approached by any other current imaging technique, and it affords a unique
opportunity for studying in vivo brain development and early diagnosis of
congenital abnormalities inadequately visualized or undetectable by prenatal
sonography. This 2-part review summarizes some of the latest developments in MR
imaging of the fetal brain and spine and its application to prenatal diagnosis.
The first part discussed the utility, safety, and technical aspects of fetal MR
imaging; the appearance of normal fetal brain development; and the role of fetal
MR imaging in the evaluation of fetal ventriculomegaly. In this second part, we
focus on additional clinical applications of fetal MR imaging, including
suspected abnormalities of the corpus callosum, malformations of cortical
development, and spine abnormalities.
PMID- 17032847
TI - Restricted diffusion in bilateral optic nerves and retinas as an indicator of
venous ischemia caused by cavernous sinus thrombophlebitis.
AB - A 44-year-old man developed bilateral blindness following severe periorbital
cellulitis and pansinusitis. CT and MR imaging demonstrated bilateral cavernous
sinus thrombosis. Diffusion-weighted imaging revealed reduced apparent diffusion
coefficient in bilateral optic nerves, suggesting optic nerve ischemia caused by
the cavernous sinus thrombophlebitis (CST). Following surgical debridement of
pansinusitis, antimicrobial therapy, and anticoagulation, the patient recovered
from the infectious episode but sustained permanent bilateral blindness. This
case shows that both retinal and optic nerve ischemia can be the cause of
blindness after CST. Arguments supporting an arterial-versus-venous origin for
the ischemia are discussed.
PMID- 17032848
TI - Fluoroscopic and CT fistulography of the first branchial cleft.
AB - We present an unusual case of a complete first branchial cleft fistula
communicating between the external auditory canal and the skin near the angle of
the mandible. CT and fluoroscopic fistulography were used to establish the
presence and course of the tract and to assist in surgical planning. The
embryology and classification of first branchial cleft anomalies are discussed,
with emphasis on the impact of imaging.
PMID- 17032849
TI - Nasopharyngeal extension of glomus tympanicum: an unusual clinical and imaging
manifestation.
AB - Nasopharyngeal extension of the glomus tympanicum is rare. Only 2 cases have been
reported in the literature to date. We present a reported case of a large
nasopharyngeal extension of recurrent glomus tympanicum, with various kinds of
imaging and histopathology and a review of the literature.
PMID- 17032850
TI - Neurothekeoma of the tongue: CT, MR, and FDG PET imaging findings.
AB - We report CT, MR, and fluorodeoxyglucose-positron-emission tomography (FDG-PET)
imaging findings of a case of cellular neurothekeoma of the tongue, a rare benign
soft-tissue tumor with neural differentiation, occurring in a 15-year-old girl.
CT and MR imaging showed a well-defined, well-enhancing submucosal soft-tissue
mass in the midline dorsal tongue. There was high FDG uptake on PET scans.
Although imaging findings are rather nonspecific, neurothekeoma may be one of
diagnostic inclusions of soft-tissue masses of the tongue in a young female
patient.
PMID- 17032851
TI - Spheric mass beneath the alar base: MR images of nasolabial cyst and schwannoma.
AB - We report 2 cases of nasolabial cyst and a case of schwannoma beneath the alar
base that required a differential diagnosis because of clinical features and MR
images that resembled the nasolabial cyst. The morphologic analysis on MR images
revealed the characteristic appearance of the nasolabial cyst, and the sagittal
MR image may be most helpful for diagnosing this rare disease.
PMID- 17032852
TI - Cerebral ischemia after filter-protected carotid artery stenting is common and
cannot be predicted by the presence of substantial amount of debris captured by
the filter device.
AB - PURPOSE: Protected carotid artery stent placement is currently under clinical
evaluation as a potential alternative to carotid endarterectomy. The current
study was undertaken to determine the incidence of new ischemic lesions found on
diffusion-weighted MR imaging (DWI) in nonselected patients after protected
carotid artery stent placement using a filter device and to determine the
potential relationship between these new ischemic lesions and the presence or
absence of a clear amount of debris captured by the neuroprotection filter
device. MATERIALS AND METHODS: A nonrandomized cohort of 52 patients (40 men, 12
women) presenting with carotid occlusive disease underwent protected carotid
artery stent placement using a filter device. DWI obtained 1 day before stent
placement was compared with that obtained 1 day after stent placement. In
addition, the macroscopic and microscopic analysis of debris captured by the
filter device during the carotid stent placement procedure was assessed. RESULTS:
Neuroprotected carotid stent placement was technically successful in all 53
procedures but was complicated by a transient ischemic attack in 3 patients
(5.6%). In 22 patients (41.5%), new ischemic lesions were found on DWI, and in 21
filter devices (39.6%), a substantial amount of atheromatous plaque and/or fibrin
was found. No clear relationship between the presence of debris captured by the
filter device and new lesions detected by DWI was found (P = .087; odds ratio
3.067). CONCLUSION: Neuroprotected carotid artery stent placement will not avoid
silent cerebral ischemia. Systematic microscopic analysis of debris captured by
the filter device has no predictive value for potential cerebral ischemia after
carotid artery stent placement.
PMID- 17032853
TI - Treatment of cerebral aneurysms with hydrogel-coated platinum coils (HydroCoil):
early single-center experience.
AB - PURPOSE: The authors report their experience using HydroCoils in the treatment of
cerebral aneurysms. METHODS: We performed a retrospective review of the first 100
nonrandomized patients (104 coiled saccular cerebral aneurysms) treated with
HydroCoils during a 27-month period. RESULTS: The average percentage of HydroCoil
by length detached in treated aneurysms was 45.5% (range, 9.9-100%). Immediate
postprocedure angiography demonstrated complete aneurysm occlusion in 34%, neck
remnant in 35%, and incomplete occlusion in 32%. Immediate procedure-related
morbidity and mortality rates were 5.8% and 0%, respectively. Angiographic follow
up was obtained in 51% (51/100 patients; 53/104 aneurysms; average, 10.3 months;
range, 0-31 months). In these 53 angiographically followed aneurysms, the overall
recanalization rate was 21%: no recanalization occurred in 23 aneurysms with
small size (<10 mm)/small neck (<4 mm) (S/S); 4 recanalizations occurred in 7
aneurysms with small size/wide neck (>4 mm) (S/W); 6 recanalizations (27%)
occurred in 22 large (L) aneurysms (>10-25 mm, 70% angiographic follow-up); and 1
giant (G) (>25 mm) aneurysm recanalized. A large proportion of aneurysms that
were not initially completely occluded were completely occluded on follow-up
(15/43 [35%]). Clinical follow-up was obtained in 73 patients (73%; average, 5.3
months; range, 0-24 months): 93% of these patients were neurologically improved
or unchanged. Three patients rehemorrhaged and 3 patients with unruptured
aneurysms developed delayed hydrocephalus. CONCLUSIONS: The overall safety
profile of HydroCoils appears acceptable. Preliminary midterm observations
suggest less coil compaction/aneurysm recanalization in large aneurysms. However,
HydroCoil-related delayed hydrocephalus is a concern.
PMID- 17032854
TI - Guglielmi detachable coils versus matrix coils: a comparison of the immediate
posttreatment results of the embolization of 364 cerebral aneurysms in 307
patients: a single-center, single-surgeon experience.
AB - BACKGROUND: Matrix coils are based on Gugliemi detachable coils (GDC) but are
covered with polyglycolic/polylactic acid. We present our experience regarding
the immediate posttreatment results of aneurysm embolization using the 2 coil
systems. PATIENTS: We embolized 219 aneurysms in 187 patients with the use of
GDCs and 145 aneurysms in 120 patients with the use of Matrix coils. Age, sex
distribution, unruptured aneurysm cases, and multiple aneurysm cases were similar
in the 2 groups. The percentage of patients in severe clinical condition was
significantly higher in the Matrix group. The mean aneurysm size was slightly
larger in the GDC group but the mean neck size was larger in the Matrix group.
RESULTS: Satisfactory occlusion (at least 90%) was achieved in 95.9% of GDC
treated aneurysms and in 98.6% of Matrix-treated aneurysms. Procedure-related
complications occurred in 19.6% of GDC procedures and in 15.6% of the Matrix ones
resulting in procedure-related mortality and morbidity of 3.7% and 2.7% for the
GDC group and 2.5% and 1.7% for the Matrix group. In the GDC group, outcome was
good (modified Rankin Scale 0-2) in 92.6% of patients with unruptured aneurysms,
in 82.6% of patients with Hunt and Hess grade I-III, and in 20.5% of those with
Hunt and Hess grade of IV-V. The respective figures were 95%, 85.7%, and 22.7% in
the Matrix group. CONCLUSION: In our series, Matrix coils have yielded slightly
better results regarding satisfactory occlusion rate and clinical outcome but
these differences are not statistically significant and probably reflect our
increased experience in aneurysm embolization during the period we used Matrix
coils.
PMID- 17032855
TI - Embolization of experimental wide-necked aneurysms with iodine-containing
polyvinyl alcohol solubilized in a low-angiotoxicity solvent.
AB - BACKGROUND AND PURPOSE: To evaluate the ready-to-use iodine-containing polyvinyl
alcohol (I-PVA) dissolved in the low angiotoxic solvent N-methyl pyrrolidone
(NMP) for embolization of porcine wide-necked aneurysms. METHODS: Fourteen broad
based carotid sidewall aneurysms were surgically constructed in 7 swine. I-PVA
(40%) in NMP was injected under temporary balloon occlusion bridging the aneurysm
neck. After 4 weeks, follow-up angiography, multisection CT angiography (MSCTA),
and 3T MR imaging including MR angiography (MRA) sequences were performed.
Afterward, harvested aneurysms were investigated histopathologically. RESULTS:
The liquid embolic was well visible under fluoroscopy and displayed a favorable
precipitation pattern, allowing for controlled polymer delivery. Ten aneurysms
(71%) were initially completely occluded, whereas in 1 aneurysm, a minimal
polymer leakage was observed. The other 4 aneurysms (29%) were almost completely
occluded. One animal suffered a lethal rebleeding from the anastomosis after
uneventful embolization. Aneurysms embolized with I-PVA could be discriminated
well from the parent artery without beam-hardening artifacts on MSCTA, and no
susceptibility artifacts were encountered on MR imaging. Histologic examination
revealed all aneurysms covered with a membrane of fibroblasts and an endothelial
cell layer while a moderate intraaneurysmal inflammatory response to the polymer
was observed. CONCLUSION: I-PVA dissolved in NMP has proved its effectiveness for
the embolization of experimental wide-necked aneurysms. This precipitating liquid
embolic offers several interesting features in that it needs no preparation
before use and no radiopaque admixtures, the latter allowing for artifact-free
evaluation of treated aneurysms with MSCTA and MRA. Moreover, it uses NMP as a
solvent, which has only a low angiotoxicity.
PMID- 17032856
TI - Initial experience with the use of intravenous eptifibatide bolus during
endovascular treatment of intracranial aneurysms.
AB - BACKGROUND AND PURPOSE: Despite systemic heparinization, thromboembolic
complications remain a major concern related to endovascular treatment of
intracranial aneurysms. We assessed the safety of intravenous eptifibatide
administered during aneurysm coiling procedures to prevent such complications.
METHODS: From August 2001 to November 2004, 298 coil embolization procedures were
performed to treat intracranial aneurysms; eptifibatide was used in 84
endovascular coil embolization procedures to treat 79 aneurysms in 74 patients.
We retrospectively reviewed medical charts, radiographic images, and procedure
notes to evaluate periprocedural complications related to eptifibatide. RESULTS:
The mean age of the 74 patients in our cohort was 55 +/- 9 years (range, 31-84)
harboring 79 aneurysms (32 ruptured/47 unruptured). Eptifibatide was given
prophylactically in 77 procedures, whereas in 7 procedures, it was given for
treatment of a thromboembolic event (visualization of an arterial branch
occlusion). A total of 5 (5.9% [total cohort]) bleeding complications related to
eptifibatide occurred during 84 procedures. Two patients (2.4% [total
cohort]/6.3% [ruptured group]) developed intracerebral hemorrhagic complications
exacerbated by eptifibatide. The other 3 (3.6% [total cohort]) patients had groin
hematomas requiring blood transfusions but had no surgical intervention. One
thromboembolic event occurred in the 77 patients receiving eptifibatide
prophylactically. CONCLUSIONS: Intravenous infusion of eptifibatide seems to be
safe to administer in patients undergoing endovascular repair of an unruptured
cerebral aneurysm. Caution must be used in patients harboring ruptured aneurysms
as intracranial bleeding complications may occur. Further study is required to
delineate the group of patients most likely to benefit from this therapy.
PMID- 17032857
TI - Saccular aneurysms on straight and curved vessels are subject to different
hemodynamics: implications of intravascular stenting.
AB - Our aim was to examine hemodynamic implications of intravascular stenting in the
canine venous pouch (sidewall or straight-vessel) and rabbit elastase (curved
vessel) aneurysm models. Flow dynamics in stented (Wallstent) and nonstented
versions were studied by using computational fluid dynamics simulations and in
vitro flow visualization, with a focus on stent placement effects on aneurysmal
flow stagnancy and flow impingement. Results show that sidewall and curved
aneurysm models have fundamentally different hemodynamics (shear-driven versus
inertia-driven) and thus stent placement outcomes.
PMID- 17032858
TI - Focal increased cortical density in immediate postembolization CT scans of
patients with intracranial aneurysms.
AB - BACKGROUND AND PURPOSE: Cortical hyperdensity was observed in the immediate
postembolization CT scans of some patients with intracranial aneurysms following
uneventful endovascular treatments. The clinical significance and possible
underlying mechanism were evaluated. MATERIAL AND METHODS: Ninety-three
consecutive patients with a total of 100 intracranial aneurysms, treated by
endosaccular packing, were studied. Seventy-four aneurysms were treated with
balloon assistance, and the remaining aneurysms were treated without balloon
assistance. All patients underwent cranial CT just before and immediately after
the endovascular treatment. If the post-treatment CT showed any new finding, an
immediate MR imaging and a repeat CT 4-6 hours after the initial posttreatment CT
were performed. Several parameters were investigated related to the presence of
cortical hyperdensity. RESULTS: Cranial CT showed focal cortical hyperdensity
following the treatment of 40/74 aneurysms (54%) with balloon remodeling and 9/26
aneurysms (34.6%) without balloon assistance. None of these patients were
symptomatic, and cortical hyperdensity resolved in the repeat CT scans. A
statistically significant relationship was observed between the presence of this
finding and the total amount of contrast material, microcatheter time, number of
balloon inflations, and total balloon inflation time. CONCLUSION: Immediate
postembolization CT may show focal cortical hyperdensity following uneventful
endovascular aneurysm treatment, most likely caused by blood-brain barrier
disruption resulting in accumulation of contrast medium. The hyperdensity was
more frequent when balloon assistance was used but was also seen in the patients
with no balloon use. It is important to differentiate this clinically
insignificant finding from possible hemorrhage, which would affect patients'
immediate postprocedural medical management.
PMID- 17032859
TI - Dynamic CT perfusion imaging with acetazolamide challenge for evaluation of
patients with unilateral cerebrovascular steno-occlusive disease.
AB - BACKGROUND AND PURPOSE: Perfusion CT (PCT) has the ability to measure
quantitative values and produce maps of cerebral blood flow (CBF), cerebral blood
volume (CBV), and mean transit time (MTT). We assessed cerebral hemodynamics by
using these parameters and acetazolamide challenge in patients with
cerebrovascular steno-occlusive disease. METHODS: Fifteen patients underwent PCT
with acetazolamide challenge. Comparison of mean CBF, CBV, and MTT was determined
between hemispheres and before and after acetazolamide challenge. Hemispheric
ratio and percent change due to acetazolamide administration were also
calculated. Absolute values and percent changes 2 SDs outside the mean from the
nonstenotic hemispheres were defined as abnormal. RESULTS: Significant decreases
in CBF (-25.1%, P = .003) and significant increases in MTT (47.1%, P < .001) were
found in stenotic hemispheres. After acetazolamide challenge, significant changes
in CBF (-39.5%, P < .001) and MTT (92.9%, P < .001) were also seen. The
acetazolamide test significantly decreased CBF hemispheric ratio (-20.3%, P <
.001) and increased MTT hemispheric ratio (30.8%, P = .002), making both maps
more asymmetric. Significance in CBF and MTT percent changes (P < .001 and P =
.005, respectively) was found between hemispheres. When CBF percent changes were
assumed to represent the true determinant of hemodynamic impairment, normal
ranges of baseline MTT value and MTT percent changes demonstrated sensitivities
of 66.7% and 100% and specificities of 58.3% and 75%, respectively, for detecting
patients with hemodynamic impairment. CONCLUSION: Parameters obtained from PCT
with acetazolamide are promising for the evaluation of cerebral hemodynamics in
patients with cerebrovascular steno-occlusive disease.
PMID- 17032860
TI - Intracranial angioplasty and stenting: long-term results from a single center.
AB - BACKGROUND AND PURPOSE: Large-vessel intracranial atherosclerotic stenosis
carries a proved stroke risk of 8%-22% per year with "best medical therapy." The
long-term clinical neurologic and angiographic outcomes of angioplasty and/or
stent placement for intracranial atherosclerosis in a consecutive series of
patients are presented. METHODS: The demographics, procedural details, procedural
outcome, and long-term neurologic follow-up in 60 consecutive patients with 71
lesions, undergoing a total of 84 procedures, were analyzed. RESULTS: Angioplasty
alone was performed in 62 procedures; 22 procedures involved stent placement. The
periprocedural stroke+death rate was 4.8%. The overall complication-free success
rate was 90.5%. Restenosis occurred in 23 lesions at a mean of 4.6 months; 13
were re-treated without complication. There were 4 strokes and 4 non-neurologic
deaths during 224 patient-years of follow-up. The annualized stroke rate was
1.8%, and the annualized stroke+all-cause death rate was 3.0%. CONCLUSIONS: The
stroke and death rates in this consecutive series of patients with severe
intracranial atherosclerotic stenosis treated with optimal endovascular therapy
are considerably less than those associated with the natural history of
intracranial atherosclerosis treated with maximal medical therapy. Intracranial
angioplasty with conditional stent placement is technically feasible and
clinically effective with a substantial reduction in long-term stroke and death.
PMID- 17032861
TI - Swine model of carotid artery atherosclerosis: experimental induction by surgical
partial ligation and dietary hypercholesterolemia.
AB - INTRODUCTION: Limited availability of a large animal model of carotid
atherosclerosis has limited preclinical evaluation of endovascular therapeutic
devices. The present study is aimed at developing such animal models with a novel
approach, emphasizing the role of hemodynamics. METHODS: Using 18 carotid
arteries from 9 miniswine, surgical partial ligation (approximately 80% stenosis)
was carried out in untreated (group I; n = 6) and balloon-injured arteries (group
II; n = 9). Three arteries were subjected to sham-operation for control (group
III; n = 3). All animals were fed with a high-fat diet until sacrifice.
Angiograms and histologic sections of the vessels were analyzed to evaluate both
models. RESULTS: Atherosclerotic changes were confirmed in 6 of 6 in group I and
6 of 9 arteries in group II, whereas all in group III remained intact. Three
arteries in group II resulted in thrombotic occlusion. Advanced plaques with
intraplaque hemorrhage and/or calcification were seen in 4 of 6 arteries in group
I but none in group II. The cross-sectional area stenosis and atherosclerotic
stage for plaques in group I were both significantly higher than that in groups
II and III. CONCLUSION: In this series, surgical partial ligation with
concomitant dietary hyperlipidemia is an appropriate experimental technique to
develop advanced atherosclerotic plaques with minimal technical complications.
This model showed no evidence of such benefits when applied in balloon-injured
arteries.
PMID- 17032862
TI - Organic solvents as vehicles for precipitating liquid embolics: a comparative
angiotoxicity study with superselective injections of swine rete mirabile.
AB - BACKGROUND AND PURPOSE: The organic solvent dimethyl-sulfoxide (DMSO), as a
commonly used vehicle for nonadhesive liquid embolics, is not devoid of local
angiotoxic effects. We compared microvascular toxicities of superselective
infusions of DMSO with potentially more compatible solvents in swine rete
mirabile. METHODS: Fourteen swine underwent angiography for superselective
catheterization of 28 arteries of the rete while electrocardiography and intra
arterial pressure were continuously monitored. The investigated solvents were
DMSO, dimethyl isosorbide (DMI), ethyl lactate, glycofurol 75, N-methyl
pyrrolidone (NMP), and solketal. Control infusion of saline ruled out catheter
induced vasospasm in all cases. Each artery of the rete was infused only once
with 0.8 mL of one of the solvents over 60 seconds. Acute angiographic and
hemodynamic consequences were evaluated. Blood samples were assessed for signs of
intravascular hemolysis. Brains and retia were harvested for gross and
histopathologic investigation. RESULTS: On the basis of the angiographic data,
DMSO induced the most pronounced vasospasm with the longest recovery period of
all solvents investigated. Ethyl lactate, glycofurol 75, and solketal elicited
less severe vasospasms and accordingly resolved much more quickly. DMI and NMP
induced only minimal vasospasms with comparably short duration. No solvent caused
significant hemodynamic alterations or hemolysis. Gross inspection of brains
showed no abnormalities, whereas histopathologic examination revealed mostly
nonspecific findings. One rete exposed to solketal displayed possible causal
histotoxic changes. CONCLUSION: DMI and NMP produced far less vasospasm than
DMSO. No changes in hemodynamic or hemolytic parameters and no histopathologic
findings were observed with infusion of these solvents.
PMID- 17032863
TI - Preoperative embolization of a cervicodorsal paraganglioma by direct percutaneous
injection of onyx and endovascular delivery of particles.
AB - We report the feasibility and efficacy of percutaneous injection of Onyx (Micro
Therapeutics, Irvine, Calif.), a nonadhesive liquid embolic agent, into an
unusually located paraganglioma, followed by endovascular embolization with
particles before surgery.
PMID- 17032864
TI - Preoperative embolization of cervical spine osteoblastomas: report of three
cases.
AB - Our aim was to describe the technique and clinical results of preoperative
embolization of cervical spine osteoblastomas. We treated 3 patients with these
tumors with transarterial embolization and subsequent surgical excision. In all 3
patients, distal access to the tumor-supplying vessels was gained with a
microcatheter and embolization was performed with polyvinyl alcohol particles. No
complications occurred. Surgical resection was performed in all patients without
relevant bleeding. The postoperative course was uneventful in all patients.
Preoperative embolization is a valuable adjunct to the surgical treatment of
osteoblastomas of the cervical spine.
PMID- 17032865
TI - 2D time-of-flight MR venography in neonates: anatomy and pitfalls.
AB - BACKGROUND AND PURPOSE: The dural venous sinuses in neonates differ from those in
adults or older children in that the caliber of venous sinuses is smaller and
there is skull molding. The aim of this retrospective study is to evaluate the
presence of flow gaps in venous sinuses in neonates on 2D time-of-flight (TOF) MR
venography (MRV). METHODS: Fifty-one neonates underwent coronal 2D TOF MRV. Nine
also had CT venography (CTV) for comparison. In 1 neonate, a further 2D TOF MRV
was performed in the sagittal plane; in another neonate, images were captured in
the axial plane; and in another, a further coronal TOF MRV with shorter echo time
was performed. RESULTS: Flow gap was seen in the posterior aspect of the superior
sagittal sinus in 35 of 51 (69%). Focal narrowing of the superior sagittal sinus,
in the region of convergence of lambdoid sutures, was detected in 7 of 51 (14%).
The right and left transverse sinuses demonstrated flow gap in 13 of 51 (25%) and
32 of 51 (63%) respectively. There was normal filling of contrast on CTV in the
superior sagittal sinus, transverse sinus and sigmoid sinus in those cases with
flow gap detected on coronal 2D TOF MRV. Right, left, and codominance of the
transverse sinuses are as follows: 32 of 51 (63%), 5 of 51 (10%), and 14 of 51
(27%), respectively. The right and left sigmoid sinuses demonstrated flow gap in
7 of 51 (14%) and 8 of 51 (16%), respectively, and the left sigmoid sinus was
absent in 1 of 51 (2%). CONCLUSION: The high proportion of flow gap in the venous
sinuses of neonates, particularly of the superior sagittal sinus, could be
attributed to the smaller caliber venous sinuses, slower venous flow, and skull
molding.
PMID- 17032866
TI - Acute necrotizing encephalopathy of childhood: correlation of MR findings and
clinical outcome.
AB - BACKGROUND AND PURPOSE: The clinical outcome of acute necrotizing encephalopathy
of childhood (ANEC), an encephalopathy characterized by symmetrical involvement
of the thalami, has historically been poor, but recent studies have reported
better outcomes. By devising a MR imaging scoring system, we determined the
relationship between characteristic MR findings and clinical outcome of patients
with ANEC. METHODS: MR studies of 12 patients with ANEC were retrospectively
reviewed. A MR imaging score was calculated for each patient according to the
presence of hemorrhage, cavitation, and location of lesions. Clinical outcome of
the patients was assessed, yielding outcome categories based on health state
utility value. Spearman rank test was used to correlate the MR imaging score with
clinical outcome of the patients. RESULTS: Statistically significant correlation
(r = 0.76, P = .001) was found between the MR score and the outcome category. The
thalami were involved in all 12 patients, brain stem in 10, cerebral white matter
in 8, and cerebellar white matter in 4. Hemorrhage was present in 5 patients and
cavitation in 4. Clinical outcome category was 1 in 2 patients, 2 in 8 patients,
and 3 in 2 patients. No patients were in category 4. CONCLUSION: There is a
significant and positive correlation between the clinical outcome and the MR
imaging score in patients with ANEC. The relation between clinical outcome and
each individual MR feature remains to be determined. Patients with ANEC may have
a better clinical outcome than has been previously reported.
PMID- 17032867
TI - Persistent diffusion abnormalities in the brain stem of three children with
mitochondrial diseases.
AB - We report 2 children (patients 1 and 2) with Kearns-Sayre syndrome and 1 (patient
3) with Leigh syndrome, who underwent serial diffusion-weighted MR imaging (DWI)
studies for 2.8 (patient 1), 4.2 (patient 2), and 1.0 years (patient 3). The DWI
revealed the persistent hyperintense signals in the pontine and mesencephalic
tegmenta. The apparent diffusion coefficient in the affected regions remained
constantly low, suggesting that cytotoxic edema and spongiform degenerations may
compose these brain stem lesions.
PMID- 17032868
TI - Dural arteriovenous malformation in a child with Bannayan-Riley-Ruvalcaba
Syndrome.
AB - Intracranial arteriovenous malformations (AVM) are a rare feature of Bannayan
Riley-Ruvalcaba syndrome (BRRS). Palencia et al reported a case of intracranial
arteriovenous malformation in a child with BRRS in a Spanish journal in 1986.
However, the occurrence of dural AVM in a patient with BRRS has not since been
addressed in the literature. Advancements in imaging and therapeutic
embolization, and the ability now to screen for phosphatase and tensin homologue
(PTEN) mutations allow us to detect and manage these patients sooner. Early
detection of intracranial AVMs is necessary because of the risk for progression
to venous ischemia and resultant neurologic damage. We present the case of a
child with headaches and periorbital venous congestion due to a dural AVM with
bilateral venous outflow occlusion who was treated with multiple embolizations,
now with interval remission of headache symptoms.
PMID- 17032869
TI - Diskography: infectious complications from a series of 12,634 cases.
AB - BACKGROUND AND PURPOSE: Diskography is commonly performed to investigate pain of
suspected diskogenic origin. Although uncommon, diskitis is a feared complication
of this procedure. We reviewed the incidence of diskitis and other infectious
complications following diskography in a large busy outpatient practice and
discuss technical aspects that may contribute to infection prevention. METHODS:
We reviewed the electronic records of all diskograms obtained at our institution
during a 12.25-year period, looking for all cases of procedure-related infection.
All diskograms had been obtained by skilled and experienced procedural
radiologists in dedicated spine-injection suites with specialized technical
staff. RESULTS: There were 12,634 examinations performed on 10,663 patients for a
total of 37,135 disk levels. Of the disk levels, 5981 were cervical; 3083,
thoracic; and 28,071, lumbar. Two cases of confirmed lumbar diskitis and no cases
of either cervical or thoracic diskitis were seen in our series. No other
infectious complications were found. The incidence of diskitis was 0.016% per
examination and 0.0054% per disk level. CONCLUSION: In skilled and experienced
hands using proper technique, diskography is a safe outpatient procedure with an
extremely low incidence of diskitis and other procedure-related infections.
PMID- 17032870
TI - The effects of cement volume on clinical outcomes of percutaneous vertebroplasty.
AB - BACKGROUND AND PURPOSE: There exists significant variability in the volume of
polymethylmethacrylate cement injected during percutaneous vertebroplasty. Larger
cement volumes injected may be associated with better clinical outcomes, but
larger volumes may also be associated with greater risk of complications related
to cement leakage. We describe an analysis of the association between clinical
and procedural variables, including cement volume injected, and the clinical
outcomes of patients treated with single-level vertebroplasty. METHODS:
Retrospective analysis of 158 patients treated with single-level vertebroplasty
was performed. Relationships among patient and procedural variables and
relationships between these variables and ordinal clinical outcome scores of pain
and medication use at postprocedure time points from 1 week to 2 years were
evaluated with bivariate and multivariable analyses. RESULTS: There was no
significant association between the volume of cement injected and the clinical
outcomes of postprocedure pain (P = .159-.871) and medication use (P = .223
.875). CONCLUSION: Vertebroplasty operators need not feel compelled to achieve
particular cement volumes injected in the pursuit of better clinical outcomes but
should strive to achieve the maximal safe filling of individual vertebral bodies.
PMID- 17032871
TI - Symptomatic refractures after vertebroplasty in patients with steroid-induced
osteoporosis.
AB - BACKGROUND AND PURPOSE: Refracture after percutaneous vertebroplasty in patients
receiving oral glucocorticoid therapy has caused some patients and referring
physicians to have negative perceptions concerning the efficacy of the initial
vertebroplasty treatment. The purpose of this study was to analyze symptomatic
refractures after vertebroplasty in patients on oral steroid therapy. We
hypothesized that the higher refracture rate of patients on oral glucocorticoid
therapy after percutaneous vertebroplasty is due not to an inadequacy of the
procedure but rather to a naturally higher predisposition of these patients to
refracture compared with patients with primary osteoporosis. METHODS: A
retrospective analysis was performed on all osteoporosis patients having initial
vertebroplasty from August 1999 to August 2003. The follow-up period was limited
to 1 year after initial vertebroplasty session, with the last follow-up date
ending in August 2004. Data were collected on 387 osteoporosis patients. RESULTS:
Of the patients with primary osteoporosis, 20.6% patients refractured whereas
37.8% of the patients with steroid-induced osteoporosis had symptomatic
refractures within 1 year of initial vertebroplasty. Relative risk of refracture
within 1 year for the patients with steroid-induced osteoporosis was 1.84
compared with the patients with primary osteoporosis. In addition, the patients
with steroid-induced osteoporosis were more likely to refracture after their
second treatment session (within 1 year of initial vertebroplasty) than those
with primary osteoporosis. CONCLUSION: Patients presenting on oral steroid
therapy at their initial vertebroplasty are almost twice more likely to have
symptomatic refractures than primary osteoporosis patients within 1 year of
initial vertebroplasty.
PMID- 17032872
TI - Lumbosacral nerve root avulsions: MR imaging demonstration of acute
abnormalities.
AB - Most of the previously reported lumbosacral nerve root avulsions presented with
pseudomeningoceles at the time of delayed initial imaging. We report a case of
traumatic lumbosacral nerve root injury associated with an isolated femur
fracture and demonstrate the evolution of pseudomeningoceles following nerve root
avulsions and edema in the perineural fat identified on the initial MR imaging.
PMID- 17032873
TI - MR diffusion tensor imaging and fiber tracking in inflammatory diseases of the
spinal cord.
AB - PURPOSE: Our aim was to study the fractional anisotropy (FA) variations and the
fiber tracking (FT) patterns observed in patients with myelitis. MATERIAL AND
METHODS: Fifteen patients with symptomatic myelitis and 11 healthy subjects were
prospectively selected. We performed T2-weighted and diffusion tensor imaging on
a 1.5T MR scanner. FA and apparent diffusion coefficient maps were computed in
both healthy subjects and patients. In each patient, we performed FT to study
pathologic aspects on this imaging method. FA data were analyzed by using z
scores. RESULTS: For the healthy subjects, averaged FA values ranged from 0.745
to 0.751. All abnormal areas seen on T2-weighted imaging had a significantly
decreased FA value. In 9 patients (60%), FA maps showed decreased FA areas,
whereas T2-weighted imaging findings were normal. These areas matched the
neurologic deficit in 33%. Eighty percent of patients had multiple decreased FA
areas. Five patients (33%) had increased FA values in normal T2-weighted areas.
CONCLUSION: We observed specific FA and FT pattern variations in patients with
myelitis.
PMID- 17032874
TI - A preliminary study of the effects of trigger timing on diffusion tensor imaging
of the human spinal cord.
AB - BACKGROUND AND PURPOSE: Diffusion tensor and diffusion-weighted spinal cord
imaging remain relatively unexplored techniques despite demonstrations that such
images can be obtained and may yield clinically relevant findings. In this study,
we examined the temporal dynamics of spinal cord motion and their impact on
diffusion tensor image quality. METHODS: Four healthy volunteers underwent phase
contrast-based velocity mapping and segmented echo-planar diffusion tensor scans
of the cervical spinal cord. Regions of interest in the cord were used to
identify the temporal patterns of motion. The delay of data acquisition after the
cardiac trigger was varied to correspond to either quiescence or motion of the
cord. RESULTS: The cervical spinal cord consistently displayed maximal velocities
in the range of 0.5 cm/s and accelerations of up to 25 cm/s(2). In both these
respects, the cervical cord values were greater than those of the medulla.
Despite this pronounced motion, approximately 40% of the cardiac cycle can be
described as relatively calm, with absolute velocities and accelerations less
than 20% of the maximum values. Confining image acquisition to this window
reduced ghosting artifacts and increased the consistency with which the dominant
direction of diffusion was along the rostral-caudal axis in both gray and white
matter of the spine. Preliminary clinical application and fiber tracking in
pathologic cases was feasible, and alterations of the diffusion properties by
multiple sclerosis lesions, tumor, and syringomyelia were seen. CONCLUSIONS:
Acquiring DTI data during the quiescent phase of spinal cord motion can reduce
ghosting artifacts and improve fiber tracking.
PMID- 17032875
TI - A nodular calcification of the alar ligament simulating a fracture in the
craniovertebral junction.
AB - We report a case of an incidental nodular calcification of the alar ligament
simulating a fracture in the craniovertebral junction of a previously healthy 24
year-old man. Three-dimensional CT and MR imaging revealed a 7.2 x 7.6 x 4.0 mm
nodular calcification in the right alar ligament with normal adjacent bony
structures. Serial cervical dynamic radiographs and open-mouth views showed that
the cervical spine was stable without any change in the calcification.
PMID- 17032876
TI - Not all age-related white matter hyperintensities are the same: a magnetization
transfer imaging study.
AB - PURPOSE: Our aim was to assess whether presumed histologic heterogeneity of age
related white matter hyperintensities (WMH) is reflected in quantitative
magnetization transfer imaging measures. MATERIALS AND METHODS: From a group of
patients participating in a double-blind placebo-controlled multicenter study on
the effect of pravastatin (PROSPER), we selected 56 subjects with WMH. WMH were
classified as periventricular WMH (PVWMH) and deep WMH (DWMH). PVWMH were
subclassified as irregular or smooth, depending on the aspect of their border.
Signal intensity of WMH on T1-weighted images was scored as iso- or hypointense.
The mean magnetization transfer ratio (MTR) value of different types of WMH was
assessed and compared. As a control group, we selected 19 subjects with no or
limited WMH. RESULTS: Mean (SE) MTR of PVWMH (frontal, 31.2% [0.2%]; occipital,
32.2% [0.2%]) was lower than that of DWMH (33.7% [0.5%]). The mean MTR of frontal
PVWMH (31.2% [0.2%]) was lower than that of occipital PVWMH (32.2% [0.2%]).
Compared with occipital PVWMH, frontal PVWMH more often had a smooth lining (72%
frontal versus 8% occipital) and an area with low signal intensity on T1-weighted
images (76% frontal versus 35% occipital). MTR did not differ between smooth
(31.1% [0.3%]) and irregular (31.6% [0.5%]) PVWMH. CONCLUSION: Age-related WMH
are heterogeneous, despite their similar appearance on T2-weighted images. By
taking into account heterogeneity of age-related WMH, both in terms of etiology
and in terms of severity of tissue destruction, one may obtain better
understanding on the causes and consequences of these lesions.
PMID- 17032877
TI - Improved delineation of glioma margins and regions of infiltration with the use
of diffusion tensor imaging: an image-guided biopsy study.
AB - BACKGROUND AND PURPOSE: The efficacy of radiation therapy, the mainstay of
treatment for malignant gliomas, is limited by our inability to accurately
determine tumor margins. As a result, despite recent advances, the prognosis
remains appalling. Because gliomas preferentially infiltrate along white matter
tracks, methods that show white matter disruption should improve this
delineation. In this study, results of histologic examination from samples
obtained from image-guided brain biopsies were correlated with diffusion tensor
images. METHODS: Twenty patients requiring image-guided biopsies for presumed
gliomas were imaged preoperatively. Patients underwent image-guided biopsies with
multiple biopsies taken along a single track that went into normal-appearing
brain. Regions of interest were determined from the sites of the biopsies, and
diffusion tensor imaging findings were compared with glioma histology. RESULTS:
Using diffusion tissue signatures, it was possible to differentiate gross tumor
(reduction of the anisotropic component, q > 12% from contralateral region), from
tumor infiltration (increase in the isotropic component, p > 10% from
contralateral region). This technique has a sensitivity of 98% and specificity of
81%. T2-weighted abnormalities failed to identify the margin in half of all
specimens. CONCLUSION: Diffusion tensor imaging can better delineate the tumor
margin in gliomas. Such techniques can improve the delineation of the radiation
therapy target volume for gliomas and potentially can direct local therapies for
tumor infiltration.
PMID- 17032878
TI - Comparing perfusion metrics obtained from a single compartment versus
pharmacokinetic modeling methods using dynamic susceptibility contrast-enhanced
perfusion MR imaging with glioma grade.
AB - BACKGROUND AND PURPOSE: Numerous different parameters measured by perfusion MR
imaging can be used for characterizing gliomas. Parameters derived from 3
different analyses were correlated with histopathologically confirmed grade in
gliomas to determine which parameters best predict tumor grade. METHODS: Seventy
four patients with gliomas underwent dynamic susceptibility contrast-enhanced MR
imaging (DSC MR imaging). Data were analyzed by 3 different algorithms. Analysis
1 estimated relative cerebral blood volume (rCBV) by using a single compartment
model. Analysis 2 estimated fractional plasma volume (V(p)) and vascular transfer
constant (K(trans)) by using a 2-compartment pharmacokinetic model. Analysis 3
estimated absolute cerebral blood flow (CBF), cerebral blood volume (CBV), and
mean transit time (MTT) by using a single compartment model and an automated
arterial input function. The Mann-Whitney U test was used make pairwise
comparisons. Binary logistic regression was used to assess whether rCBV, V(p),
K(trans), CBV, CBF, and MTT can discriminate high- from low-grade tumors.
RESULTS: rCBV was the best discriminator of tumor grade ype, followed by CBF,
CBV, and K(trans). Spearman rank correlation factors were the following: rCBV =
0.812 (P < .0001), CBF = 0.677 (P < .0001), CBV = 0.604 (P < .0001), K(trans) =
0.457 (P < .0001), V(p) = 0.301 (P =.009), and MTT = 0.089 (P = .448). rCBV was
the best single predictor, and K(trans) with rCBV was the best set of predictors
of high-grade glioma. CONCLUSION: rCBV, CBF, CBV K(trans), and V(p) measurements
correlated well with histopathologic grade. rCBV was the best predictor of glioma
grade, and the combination of rCBV with K(trans) was the best set of metrics to
predict glioma grade.
PMID- 17032879
TI - Transient splenial lesion of the corpus callosum in clinically mild influenza
associated encephalitis/encephalopathy.
AB - BACKGROUND: Reversible lesions in the splenium of the corpus callosum (SCC),
caused by various agents such as influenza, rotavirus, Escherichia coli, mumps,
and adenovirus, were previously defined in a handful of cases. We present 5 cases
with transient diffusion restriction of the SCC associated with influenza A virus
infection. MATERIALS AND METHODS: Five patients with influenza-associated
encephalitis/encephalopathy and sudden-onset neurologic symptoms following a
prodromal flulike episode were examined by MR and diffusion-weighted imaging
(DWI). RESULTS: Three patients, who had drowsiness and new-onset convulsions,
recovered spontaneously without any medication. In the other 2 seizure-free
patients, 1 had trigeminal neuralgia and headache and the other had facial
numbness and left upper monoparesis. All patients had round well-defined ovoid
hyperintense splenial lesions (14.94 +/- 1.87 mm) on DWI with a significantly low
apparent diffusion coefficient (ADC) of 0.41 +/- 0.05 x 10(-3) mm(2)/s compared
with 0.84 +/- 0.01 x 10(-3) mm(2)/s of normal-appearing white matter. In the
patient with a motor deficit, additional lesions were found in the cerebral deep
white matter. The high signal intensity of the splenial and deep white matter
lesions on DWI completely disappeared on follow-up studies, and ADC values also
improved, returning to those of normal-appearing white matter on days 8-11.
Clinically, all patients completely recovered on days 4-9. CONCLUSION: A
transient lesion of the SCC is a significant but nonspecific finding. It is
probably due to edematous and/or inflammatory changes of the SCC. It may be the
only detectable change in patients with good prognosis, indicating a clinically
mild form of encephalitis/encephalopathy.
PMID- 17032880
TI - Higher prevalence of cortical lesions observed in patients with acute stroke
using high-resolution diffusion-weighted imaging.
AB - Ischemic lesion conspicuity on routine diffusion-weighted imaging (DWI, 30
seconds) was compared with an improved sequence (high-resolution DWI [DWI-HR],
256 seconds) having increased spatial resolution and signal to noise and
decreased eddy current artifact in 42 patients with acute ischemic stroke. Total
lesion volumes were similar; however, twice as many lesions were identified on
DWI-HR, predominately in cortical gray matter. Modest improvements to imaging
resulted in increased conspicuity, potentially affecting diagnosis, suspected
pathogenic mechanism, and therapeutic decision.
PMID- 17032881
TI - Reversed discrepancy between CT and diffusion-weighted MR imaging in acute
ischemic stroke.
AB - PURPOSE: We sought to determine whether an early CT ischemic lesion showing
parenchymal hypoattenuation might be undetectable on diffusion-weighted imaging
(DWI) in acute cerebral ischemia. MATERIALS AND METHODS: We retrospectively
evaluated CT and MR images of 70 consecutive patients with acute middle cerebral
artery (MCA) infarction. All patients underwent CT and MR imaging within 6 hours
of symptom onset. We determined the presence of reversed discrepancy (RD),
defined as an early ischemic lesion showing parenchymal hypoattenuation on CT but
no hyperintensity on DWI. CT Hounsfield units (HU), apparent diffusion
coefficients (ADCs), and perfusion parameters were calculated for RD lesions.
RESULTS: RD was found in 9 (12.9%) patients and at basal ganglia (89%). The mean
HU of RD lesion was lower than that of normal tissue (DeltaHU, 2.33 +/- 0.74, P <
.001). RD lesions showed no significant decrease of ADC (ADC ratio, 0.97 +/-
0.07, P = .059) and cerebral blood flow (relative CBF, 0.87 +/- 0.20, P > 0.05).
Delayed DWI hyperintensity occurred in 8 (88.8%) RD lesions, and all lesions
progressed to infarction. In 6 (66%) of 9 patients with RD, Alberto Stroke
Program Early CT scores of ischemic lesions were lower on CT than those on DWI.
CONCLUSION: RD was uncommonly found mainly in basal ganglia, and all RD lesions
progressed to infarction at follow-up. Early CT ischemic lesion showing
parenchymal hypoattenuation may be undetectable on DWI, and DWI may underestimate
extent of severe ischemic tissue in patients with acute MCA infarction.
PMID- 17032882
TI - Calcified cerebral emboli.
AB - Intracranial calcifications may represent calcified cerebral emboli. Calcified
emboli may be overlooked even though cerebral CT is widely used as a stroke
assessment. We report 4 cases of calcified cerebral emboli and demonstrate the
value of CT in the diagnosis and temporal evaluation of such emboli.
PMID- 17032884
TI - Normal-appearing white matter changes vary with distance to lesions in multiple
sclerosis.
AB - BACKGROUND AND PURPOSE: Multiple sclerosis (MS) disease processes in normal
appearing white matter (NAWM) may be different close to MR-visible lesions than
farther from these lesions. We aimed to investigate the relationship of NAWM
changes to the distance to the lesions. METHODS: We measured B(1)-corrected T1
and magnetization transfer ratio (MTR) maps in 63 patients with MS (11 primary
progressive, 34 relapsing-remitting, 18 secondary progressive). We used histogram
analyses to assess the global properties of lesions, of 4 consecutive 1-mm pixel
layers of NAWM around the lesions, and of distant NAWM located at least 4-mm from
lesions in all directions. In 22 healthy controls, we measured white matter MTR
and T1 histograms. Histogram parameters were statistically analyzed by using a
linear mixed model. RESULTS: The first and second NAWM pixel layers around the
lesions had a significantly lower MTR histogram peak position than distant NAWM,
whereas T1 histogram peak position was similar between all types of NAWM.
Furthermore, MTR histograms of distant NAWM were statistically indistinguishable
from those of control white matter, whereas T1 histograms of distant NAWM had
significantly decreased peak height for relapsing-remitting MS and secondary
progressive MS and significantly increased peak position for secondary
progressive MS. CONCLUSION: Our results may suggest that axonal damage and
demyelination in NAWM mainly arise as a secondary result of visible lesions, with
the largest effect close to these lesions. NAWM disease farther from the lesions
may be mainly characterized by subtle blood-brain barrier damage, with leakage of
fibrinogen into the parenchyma and microplaque formation, processes that are
detected with T1 but not with MTR.
PMID- 17032883
TI - Diffusion anisotropy changes in the brains of professional boxers.
AB - BACKGROUND AND PURPOSE: Professional boxing may result in brain injury. We
hypothesize that quantitative MR diffusion imaging may be useful in determining
early white matter changes. METHODS: Forty-nine professional boxers (age 30 +/-
4.5 years) and 19 healthy control subjects (age 32 +/- 9.5 years) were imaged on
a clinical 1.5T scanner. None of the subjects had neurologic disorder or deficit.
The average diffusion constant (D(av)) and diffusion anisotropy (FA) were
determined pixel by pixel. Regional diffusion measurements were done in the
corpus callosum (CC) and internal capsule (IC). The whole brain diffusion
constant (BD(av)) was also determined. Student t test was used to analyze the
diffusion difference between boxers and the healthy control subjects. P < .05 was
considered statistically significant. RESULTS: Of the 49 professional boxers, 42
had normal conventional MRIs. The remaining 7 boxers had abnormal MR imaging
findings dominated by nonspecific white matter disease. There was a significant
difference in diffusion and anisotropy measurements in all the boxers compared
with the healthy control subjects. In the boxer group, BD(av) increased and FA
decreased significantly in the CC and posterior limb of IC. The measured FA and
D(av) inversely correlated in regions of CC and IC in boxers but not in healthy
control subjects. BD(av) also robustly correlated with both FA and D(av) in the
splenium of CC in boxers. CONCLUSION: Increased BD(av) and the decreased FA in
the CC and IC may represent preclinical signs of subtle brain injury in
professional boxers.
PMID- 17032885
TI - A rare anatomic variant of a solitary internal carotid artery associated with
moyamoya phenomenon of the middle cerebral artery.
AB - A case of a congenital solitary internal carotid artery with complicated
anastomosis is presented. This rare anomaly was an incidental finding at cerebral
angiography in a patient with a poor-grade subarachnoid hemorrhage and a ruptured
anterior communicating artery aneurysm.
PMID- 17032887
TI - Modeling the impact of adjuvant therapy and screening mammography on U.S. breast
cancer mortality between 1975 and 2000: introduction to the problem.
PMID- 17032888
TI - Dissemination of adjuvant multiagent chemotherapy and tamoxifen for breast cancer
in the United States using estrogen receptor information: 1975-1999.
AB - BACKGROUND: Clinical trials have shown tamoxifen to be effective only in women
with estrogen receptor (ER)-positive tumors. In a previous model, trends in the
utilization of adjuvant therapy were modeled only as a function of age and stage
of the disease and not ER status. In this paper, we integrate this previous
estimate on the use of adjuvant systemic therapy for breast cancer in the United
States with information on ER status from the Patterns of Care (POC) data to
estimate the dissemination of adjuvant therapy for women with different ER-status
tumors. We also summarize efficacy of adjuvant systemic therapy reported in the
overviews of early breast cancer clinical trials. These two inputs, dissemination
and efficacy, are key pieces for models that investigate the effect of breast
cancer adjuvant therapy on the decline of U.S. breast cancer mortality. METHODS:
The adjustments to the previous models are calculated using the POC data on 7116
women with breast cancer diagnosed from 1987 to 1991 and in 1995 who were
randomly selected from the Surveillance, and Epidemiology, and End Results (SEER)
program registries. The POC data provide more accurate information on treatment
and clinical variables (e.g., ER status) than the SEER data because medical
records are reabstracted and further verified with treating physicians. RESULTS:
Use of multiagent chemotherapy is higher for younger women (<50 years) and for
women whose tumors were shown to be ER negative or borderline. The use of
tamoxifen is higher among older women and women with ER-positive tumors. After
1980 the combined use of multiagent chemotherapy and tamoxifen for women
diagnosed with breast cancer at ages 69 or younger increased more for women whose
tumors were ER status positive or unknown than ER status negative. Older women
(>69 years) seem to receive almost exclusively tamoxifen irrespective of ER
status, except for a small percentage of those with more advanced stages (II- and
II+/IIIA) who also receive multiagent chemotherapy. DISCUSSION: The estimated
dissemination trends by ER status, based on modeling the POC data, reveal that
treatment strategies with demonstrated efficacy in clinical trials have been
adopted into practice. The dissemination and efficacy are the two factors
necessary to input into models to determine the population impact of these
therapies on U.S. breast cancer mortality. The largest decline in mortality would
be expected for younger women (<60 years) with ER-positive tumors or whose tumors
are of unknown status because of the largest efficacy and dissemination of
adjuvant therapy in this group.
PMID- 17032889
TI - Competing risks to breast cancer mortality.
AB - BACKGROUND: Simulation models analyzing the impact of treatment interventions and
screening on the level of breast cancer mortality require an input of mortality
from causes other than breast cancer, or competing risks. METHODS: This chapter
presents an actuarial method of creating cohort life tables using published data
that removes breast cancer as a cause of death. RESULTS: Mortality from causes
other than breast cancer as a percentage of all-cause mortality is smallest for
women in their forties and fifties, as small as 85% of the all-cause rate,
although the level and percentage of the impact varies by birth cohort.
CONCLUSION: This method produces life tables by birth cohort and by age that are
easily included as a common input by the various CISNET modeling groups to
predict mortality from other causes. Attention to removing breast cancer
mortality from all-cause mortality is worthwhile, because breast cancer mortality
can be as high as 15% at some ages.
PMID- 17032890
TI - Changing patterns in breast cancer incidence trends.
AB - Incidence rates for breast cancer in U.S. women have steadily increased for
decades, but the reasons are not well understood. A recent upturn in these trends
suggests that one component may be the effect of more aggressive screening in the
population. The age-period-cohort framework, in which the temporal components
associated with year of diagnosis and generation are evaluated, can assist in
interpreting the elements associated with these trends. A unique approach for
exploring other ways of partitioning the contribution of the different temporal
components is described and applied to breast cancer incidence data (ICDO 174.0
174.9) from the Surveillance, Epidemiology and End Results (SEER) registries.
Single-year intervals for age and year of diagnosis were used to fit models that
provide estimates of the trends associated with the individual temporal elements.
A log-linear model for age, period, and cohort was fitted using Poisson
regression, and estimates of the separate time trends were calculated. The trends
with period increased after 1982, when more aggressive screening began, and the
trend is steeper for women older than 40 years. Cohort trends have increased
steadily, although recent cohorts appear to be somewhat flat for women aged 50
years or younger, whereas the trend for those older than 50 years have continued
to increase. Estimates of cohort trends in rates are also provided by
extrapolating what would have occurred had there been no period trend before or
after 1982, thus providing an estimate of the magnitude of the upturn that
occurred after the recent emphasis on screening.
PMID- 17032891
TI - Additional common inputs for analyzing impact of adjuvant therapy and mammography
on U.S. mortality.
AB - In estimating the impact of mammography and adjuvant treatment on U.S. breast
cancer mortality rates, several parameters were common to all the Cancer
Intervention and Surveillance Modeling Network (CISNET) models participating in
the breast cancer base case. Models either used the parameters directly as input
or calibrated their models to reproduce the common set of parameters. This
chapter describes the common input parameters that are not specifically discussed
elsewhere in the monograph.
PMID- 17032892
TI - Modeling the impact of treatment and screening on U.S. breast cancer mortality: a
Bayesian approach.
AB - BACKGROUND: Breast cancer mortality (BCM) in the United States declined from 33.1
per 100,000 women in 1990 to 26.6 per 100,000 women in 2000, yielding a 19.6%
relative decline in BCM since 1990. Our goal is to apportion this decline between
screening and therapy and to be able to state with some certainty that these
interventions affected this decline. METHODS: We started with an age-appropriate
population of 2,000,000 women in 1975 and monitored these women through 2000. On
the basis of population data each year, we assigned screening and breast cancer
to women. If a woman was diagnosed with breast cancer, we simulated a lifetime
for her with death from breast cancer, and we modified this lifetime depending on
the use of adjuvant therapy and whether the cancer was screen-detected. A woman's
lifetime was taken as the minimum of her lifetime with death from breast cancer
and her simulated natural lifetime. We used Bayesian simulation modeling, which
allows for associating probability distributions with our estimates. RESULTS: We
calculated the probabilities that screening mammography and adjuvant therapy
contributed to the observed decline in BCM to be 90% and 99%, respectively. The
posterior mean reduction in BCM due to screening is 10.6% +/- 5.7% and due to
therapy is 19.5% +/- 5.4%. The decrease in the hazard of BCM due to tamoxifen use
for ER-positive tumors is 37% +/- 14% and that due to adjuvant (nontaxane)
chemotherapy is 15% +/- 14%. DISCUSSION: The spread in our posterior
distributions reflect the uncertainty present in the data sources available to
us. However, despite this uncertainty we conclude a high probability that both
screening and improvements in therapy contributed to the reduction in BCM
observed in the United States from 1990 to 2000.
PMID- 17032893
TI - The Wisconsin Breast Cancer Epidemiology Simulation Model.
AB - The Wisconsin Breast Cancer Epidemiology Simulation Model is a discrete-event,
stochastic simulation model using a systems-science modeling approach to
replicate breast cancer incidence and mortality in the U.S. population from 1975
to 2000. Four interacting processes are modeled over time: (1) natural history of
breast cancer, (2) breast cancer detection, (3) breast cancer treatment, and (4)
competing cause mortality. These components form a complex interacting system
simulating the lives of 2.95 million women (approximately 1/50 the U.S.
population) from 1950 to 2000 in 6-month cycles. After a "burn in" of 25 years to
stabilize prevalent occult cancers, the model outputs age-specific incidence
rates by stage and age-specific mortality rates from 1975 to 2000. The model
simulates occult as well as detected disease at the individual level and can be
used to address "What if?" questions about effectiveness of screening and
treatment protocols, as well as to estimate benefits to women of specific ages
and screening histories.
PMID- 17032894
TI - The SPECTRUM population model of the impact of screening and treatment on U.S.
breast cancer trends from 1975 to 2000: principles and practice of the model
methods.
AB - OBJECTIVE: This stochastic simulation model was developed to estimate the impact
of screening and treatment diffusion on U.S. breast cancer mortality between 1975
and 2000. MODELING APPROACH: We use an event-driven continuous-time state
transition model. Women who are destined to develop breast cancer may be screen
detected, present with symptoms, or die of other causes before cancer is
diagnosed. At presentation, the cancer has a stage assigned on the basis of mode
of detection. Cancers are assumed to be estrogen receptor (ER) positive or
negative. Data on screening and treatment diffusion are based on national
datasets; other parameters are based on a synthesis of the evidence available in
the literature. MODEL METHODS: The model is calibrated to predict incidence and
stage distribution (in situ, local, regional, and distant). Other than screening
or treatment, background events that affect mortality are not explicitly modeled
but are captured in the deviation between model projections of mortality trends
and actual trends. We assume that: 1) tumors progress more slowly in older age
groups, 2) screen- and clinically detected disease have the same survival
conditional on age and stage, 3) women do not die of breast cancer within the
"lead time" period, 4) screening benefits are captured by shifts in stage at
diagnosis, 4) tamoxifen benefits only ER-positive women, and 5) preclinical
sojourn time and dwell times in each of the clinical stages are stochastically
independent. MODEL RESULTS: Dissemination of screening and therapeutic advances
had a substantial impact on mortality trends. We estimate that, by the year 2000,
diffusion of screening lowered mortality by 12.4% and treatment improvements and
dissemination lowered mortality by 14.6%. CONCLUSIONS: Models such as this one
can be useful to translate clinical trial findings to general populations. This
model can also be used inform policy debates about how to best achieve targeted
reductions in breast cancer morbidity and mortality.
PMID- 17032895
TI - The MISCAN-Fadia continuous tumor growth model for breast cancer.
AB - The MISCAN-Fadia model was used to analyze the impact of screening and adjuvant
treatment on U.S. breast cancer mortality between 1975 and 2000. MISCAN-Fadia
uses the concept of "fatal diameter" to model survival and screening benefit and
is based on continuous tumor growth. It consists of four major components:
population, natural history, screening, and treatment. Population parameters were
quantified using U.S. population data. Most natural history and screening
parameters were fitted to the Swedish Two County screening trial data; some were
based on Surveillance, Epidemiology, and End Results data. Adjuvant treatment
parameters were quantified using data from the Early Breast Cancer Trialists'
Collaborative Group's meta-analysis. The simulated trend in incidence matches the
observed trend reasonably well; the simulated mortality is equal to the observed
in 1975 but becomes increasingly too high in 2000. We estimate that screening
leads to a 15% and adjuvant treatment to a 21% mortality reduction in the year
2000.
PMID- 17032896
TI - The University of Rochester model of breast cancer detection and survival.
AB - This paper presents a biologically motivated model of breast cancer development
and detection allowing for arbitrary screening schedules and the effects of
clinical covariates recorded at the time of diagnosis on posttreatment survival.
Biologically meaningful parameters of the model are estimated by the method of
maximum likelihood from the data on age and tumor size at detection that resulted
from two randomized trials known as the Canadian National Breast Screening
Studies. When properly calibrated, the model provides a good description of the
U.S. national trends in breast cancer incidence and mortality. The model was
validated by predicting some quantitative characteristics obtained from the
Surveillance, Epidemiology, and End Results data. In particular, the model
provides an excellent prediction of the size-specific age-adjusted incidence of
invasive breast cancer as a function of calendar time for 1975-1999. Predictive
properties of the model are also illustrated with an application to the dynamics
of age-specific incidence and stage-specific age-adjusted incidence over 1975
1999.
PMID- 17032897
TI - A stochastic model for predicting the mortality of breast cancer.
AB - Consider a cohort of women, identified by year of birth, some of whom will
eventually be diagnosed with breast cancer. A stochastic model is developed for
predicting the U.S. breast cancer mortality that depends on advances in therapy
and dissemination of mammographic screening. The predicted mortality can be
compared with the same cohort having usual care with no screening program and
absence of modern therapy, or a cohort in which only a proportion participate in
a screening program and have modern therapy. The model envisions that a woman may
be in four health states: i.e., 1) no disease or breast cancer that cannot be
diagnosed (S0), 2) preclinical state (Sp), 3) clinical state (Sc), and 4) disease
specific death (Sd). The preclinical disease refers to breast cancer that is
asymptomatic but that may be diagnosed with a special exam. The clinical state
refers to symptomatic disease diagnosed under usual care. One of the basic
assumptions of the model is that the disease is progressive; i.e., the
transitions for the first three states are S0-->Sp-->Sc. The other basic
assumption is that any reduction in mortality associated with earlier diagnosis
is due to a stage shift in diagnosis; i.e., early diagnosis results in a larger
proportion of earlier stage patients. The model is used to predict changes in
female breast cancer mortality in the U.S. women for 1975-2000. The model is
general and may predict mortality for other chronic diseases that satisfy the two
basic assumptions.
PMID- 17032899
TI - A comparative review of CISNET breast models used to analyze U.S. breast cancer
incidence and mortality trends.
AB - The CISNET Breast Cancer program is a National Cancer Institute-sponsored
collaboration composed of seven research groups that have modeled the impact of
screening and adjuvant treatment on trends in breast cancer incidence and
mortality over the period 1975-2000 (base case). This collaboration created a
unique opportunity to make direct comparison of results from different models of
population-based cancer screening produced in response to the same question.
Comparing results in all but the most cursory way necessitates comparison of the
models themselves. Previous chapters have discussed the models individual in
detail. This chapter will aid the reader in understanding key areas of difference
between the models. A focused analysis of differences and similarities between
the models is presented with special attention paid to areas deemed most likely
to contribute substantially to the results of the target analysis.
PMID- 17032898
TI - A stochastic simulation model of U.S. breast cancer mortality trends from 1975 to
2000.
AB - BACKGROUND: We present a simulation model that predicts U.S. breast cancer
mortality trends from 1975 to 2000 and quantifies the impact of screening
mammography and adjuvant therapy on these trends. This model was developed within
the Cancer Intervention and Surveillance Network (CISNET) consortium. METHOD: A
Monte Carlo simulation is developed to generate the life history of individual
breast cancer patients by using CISNET base case inputs that describe the secular
trend in breast cancer risk, dissemination patterns for screening mammography and
adjuvant treatment, and death from causes other than breast cancer. The model
generates the patient's age, tumor size and stage at detection, mode of
detection, age at death, and cause of death (breast cancer versus other) based in
part on assumptions on the natural history of breast cancer. Outcomes from
multiple birth cohorts are summarized in terms of breast cancer mortality rates
by calendar year. RESULT: Predicted breast cancer mortality rates follow the
general shape of U.S. breast cancer mortality rates from 1975 to 1995 but level
off after 1995 as opposed to following an observed decline. Sensitivity analysis
revealed that the impact adjuvant treatment may be underestimated given the lack
of data on temporal variation in treatment efficacy. CONCLUSION: We developed a
simulation model that uses CISNET base case inputs and closely, but not exactly,
reproduces U.S. breast cancer mortality rates. Screening mammography and adjuvant
therapy are shown to have both contributed to a decline in U.S. breast cancer
mortality.
PMID- 17032900
TI - Impact of mammography on U.S. breast cancer mortality, 1975-2000: are
intermediate outcome measures informative?
AB - Seven models have estimated the contribution of screening to the decrease in U.S.
breast cancer mortality between 1975 and 2000. We will investigate whether the
model estimates of the mortality reduction due to screening are associated with
intermediate outcome measures (IOMs). Detection rates at screening, 1- and 2-year
sensitivity, program sensitivity, and incidence of advanced tumors are used as
IOMs. Moreover, the model parameters preclinical duration and sensitivity are
analyzed. The correlation of IOMs with mortality is assessed for actual U.S.
screening and for an intensive screening scenario, with annual screening at ages
40-79 years with 100% participation. Also, 12 alternative screening scenarios are
run for one of the models, and within-model correlation between IOMs and
mortality reduction is described. Resulting correlations between IOMs and
mortality reduction are mostly weak. For 2-year sensitivity and the incidence of
advanced tumors, correlations are high in the intensive screening scenario.
Within-model correlations are strong for incidence of advanced tumors and program
sensitivity. Intermediate outcome measures have limited potential in predicting
the impact of mammographic screening on mortality. Incidence of advanced tumors
and program sensitivity are measures that merit further consideration as
surrogates for mortality reduction.
PMID- 17032901
TI - Impact of adjuvant therapy and mammography on U.S. mortality from 1975 to 2000:
comparison of mortality results from the cisnet breast cancer base case analysis.
AB - The CISNET breast cancer program is a consortium of seven research groups
modeling the impact of various cancer interventions on the national trends of
breast cancer incidence and mortality. Each of the modeling groups participated
in a CISNET breast cancer base case analysis with the objective of assessing the
impact of mammography and adjuvant therapy on breast cancer mortality between
1975 and 2000. The comparative modeling approach used to address this question
allowed for a unique view into the process of modeling. Results shown here expand
on those recently reported in the New England Journal of Medicine (Berry et al.,
N Engl J Med 2005;353:1784-92) by presenting mortality impact in several
different ways to facilitate comparisons between models. Comparisons of each
group's results in the context of modeling assumptions made during the process
gave insight into how specific model assumptions may have affected the results.
The median estimate for the percent decline in breast cancer mortality due to
mammography was 15% (range of 8%-23%), and the median estimate for the percent
decline in mortality due to adjuvant treatment was 19% (range of 12%-21%). A
detailed discussion of the differences in modeling approaches and how those
differences may have influenced the mortality results concludes the chapter.
PMID- 17032902
TI - Modeling cancer natural history, epidemiology, and control: reflections on the
CISNET breast group experience.
PMID- 17032903
TI - Amino acid residues in the P2X7 receptor that mediate differential sensitivity to
ATP and BzATP.
AB - Agonist properties of the P2X7 receptor (P2X7R) differ strikingly from other P2X
receptors in two main ways: high concentrations of ATP (> 100 microM) are
required to activate the receptor, and the ATP analog 2',3'-O-(4-benzoyl
benzoyl)ATP (BzATP) is both more potent than ATP and evokes a higher maximum
current. However, there are striking species differences in these properties. We
sought to exploit the large differences in ATP and BzATP responses between rat
and mouse P2X7R to delineate regions or specific residues that may be responsible
for the unique actions of these agonists at the P2X7R. We measured membrane
currents in response to ATP and BzATP at wild-type rat and mouse P2X7R, at
chimeric P2X7Rs, and at mouse P2X7Rs bearing point mutations. Wild-type rat P2X7R
was 10 times more sensitive to ATP and 100 times more sensitive to BzATP than
wild-type mouse P2X7R. We found that agonist EC50 values were determined solely
by the ectodomain of the P2X7R. Two segments (residues 115-136 and 282-288), when
transposed together, converted mouse sensitivities to those of rat. Point
mutations through these regions revealed a single residue, asparagine284, in the
rat P2X7R that fully accounted for the 10-fold difference in ATP sensitivity,
whereas the 100-fold difference in BzATP sensitivity required the transfer of
both Lys127 and Asn284 from rat to mouse. Thus, single amino acid differences
between species can account for large changes in agonist effectiveness and
differentiate between the two widely used agonists at P2X7 receptors.
PMID- 17032904
TI - The effect of low pH on breast cancer resistance protein (ABCG2)-mediated
transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic
acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models.
AB - Some cellular uptake systems for (anti)folates function optimally at acidic pH.
We have tested whether this also applies to efflux from cells by breast cancer
resistance protein (BCRP; ABCG2), which has been reported to transport folic
acid, methotrexate, and methotrexate di- and triglutamate at physiological pH.
Using Spodoptera frugiperda-BCRP membrane vesicles, we showed that the ATP
dependent vesicular transport of 1 muM methotrexate by BCRP is 5-fold higher at
pH 5.5 than at physiological pH. The transport of methotrexate was saturable at
pH 5.5, with apparent Km and Vmax values of 1.3 +/- 0.2 mM and 44 +/- 2.5 nmol/mg
of protein/min, respectively, but was linear with drug concentration at pH 7.3 up
to 6 mM methotrexate. In contrast to recent reports, we did not detect transport
of methotrexate diglutamate at physiological pH, but we did find transport at pH
5.5. We also found that 7-hydroxy-methotrexate, the major metabolite of
methotrexate, is transported by BCRP both at physiological pH and (more
efficiently) at low pH. The pH effect was also observed in intact BCRP
overexpressing cells: we found a 3-fold higher level of resistance to both
methotrexate and the prototypical BCRP substrate mitoxantrone at pH 6.5 as at
physiological pH. Furthermore, with MDCKII-BCRP monolayers, we found that
resveratrol, which is a neutral compound at pH < or = 7.4, is efficiently
transported by BCRP at pH 6.0, whereas we did not detect active transport at pH
7.4. We conclude that BCRP transports substrate drugs more efficiently at low pH,
independent of the dissociation status of the substrate.
PMID- 17032905
TI - Amphetamine induces a calcium/calmodulin-dependent protein kinase II-dependent
reduction in norepinephrine transporter surface expression linked to changes in
syntaxin 1A/transporter complexes.
AB - Norepinephrine (NE) transporters (NETs) are high-affinity transport proteins that
mediate the synaptic clearance of NE after vesicular release. NETs represent a
major therapeutic target for antidepressants and are targets of multiple
psychostimulants including amphetamine (AMPH) and cocaine. Recently, we
demonstrated that syntaxin 1A (SYN1A) regulates NET surface expression and,
through binding to the transporter's NH(2) terminus, regulates transporter
catalytic function. AMPH induces NE efflux and may also regulate transporter
trafficking. We monitored NET distribution and function in catecholaminergic cell
lines (CAD) stably transfected with either full-length human NET (CAD-hNET) or
with an hNET N-terminal deletion (CAD-hNETDelta(28-47) cells). In hNET-CAD cells,
AMPH causes a slow and small reduction of surface hNET with a modest increase in
hNET/SYN1A associations at the plasma membrane. In contrast, in CAD-hNETDelta(28
47) cells, AMPH induces a rapid and substantial reduction in surface hNETDelta(28
47) accompanied by a large increase in plasma membrane hNETDelta(28-47)/SYN1A
complexes. We also found that AMPH in CAD-hNETDelta(28-47) cells induces a robust
increase in cytosolic Ca2+ and concomitant activation of calcium/calmodulin
dependent protein kinase II (CaMKII). Inhibition of either the increase in
intracellular Ca2+ or CaMKII activity blocks AMPH-stimulated hNETDelta(28-47)
trafficking and the formation of hNETDelta(28-47)/SYN1A complexes. Here, we
demonstrate that AMPH stimulation of CAMKII stabilizes an hNET/SYN1A complex.
This hNET/SYN1A complex rapidly redistributes, upon AMPH treatment, when
mechanisms supported by the transporter's NH2 terminus are eliminated.
PMID- 17032906
TI - Impact of residence on prevalence and intensity of prescription drug use among
older adults.
AB - BACKGROUND: Higher levels of morbidity among older adults result in greater need
for pharmaceutical products and pharmacy services compared with the need in the
general population. Rural residents reportedly have reduced access to healthcare
services secondary to transportation difficulties, a limited supply of healthcare
workers and facilities, and financial constraints. OBJECTIVE: To examine
differences in the prevalence and intensity of prescription pharmaceutical use
among urban and rural older adults in Manitoba, Canada. METHODS: Participant data
from the 1996/1997 Manitoba Study of Health and Aging were linked to
pharmaceutical claims data recorded in Manitoba Health's Drug Program Information
Network. The effect of residence on the prevalence and intensity of drug use was
determined, in addition to the effects of other sociodemographic characteristics,
measures of health, and health service utilization. RESULTS: The prevalence of
prescription pharmaceutical use did not differ between urban and rural residents
(90.6% vs 89.5%, respectively; p = 0.60). Users of home-care services (OR 1.93;
95% CI 1.09 to 3.39), those who perceived their income as adequate (2.38; 95% CI
1.09 to 5.17), and those with a higher number of chronic health problems (1.42;
95% CI 1.26 to 1.62) were significantly more likely to access prescription
medications. Rural and urban residents were equally likely to be high users of
prescription drugs (21.3% vs 20.0%, respectively; p = 0.64). CONCLUSIONS: Poor
health status is associated with a higher prevalence and intensity of use of
prescription drugs among older Manitobans. Rural residence is not a barrier to
receipt of prescription pharmaceuticals.
PMID- 17032907
TI - Acute renal failure associated with vancomycin- and tobramycin-laden cement in
total hip arthroplasty.
AB - OBJECTIVE: To describe 2 cases of acute renal failure (ARF) associated with the
use of antibiotic-laden cement incorporated in total hip arthroplasties (THA).
CASE SUMMARIES: An 82-year-old female received a right THA with antibiotic-laden
cement spacers. She developed ARF 5 months following implantation, concurrent
with an elevated serum tobramycin concentration of 5.5 microg/mL. After
explantation of the prosthesis and spacers, serum creatinine and antibiotic
concentrations decreased to within normal limits. A 79-year-old male received
antibiotic-laden cement spacers in a revision of his right THA due to infection.
ARF developed 1 1/2 months after the revision; a serum tobramycin concentration
was 2.9 microg/mL. Serum creatinine and antibiotic serum concentrations decreased
to within normal limits with explantation. DISCUSSION: More than 250 000 joint
replacements are performed yearly in the US. A common complication is infection,
which occurs in 1-2% of primary replacements and 3-4% of revisions of previously
infected prostheses. Antibiotic-laden cement is used for prosthesis placement to
prevent or treat infection, while minimizing systemic drug exposure. Both
patients described here received antibiotic-laden spacers during THA and
subsequently developed ARF in conjunction with elevated serum tobramycin
concentrations. Use of the Naranjo probability scale and consideration of
possible contributing factors suggest a probable association of the antibiotic
laden cement and the development of ARF in these patients. CONCLUSIONS:
Antibiotic-laden cement with aminoglycosides and/or vancomycin has the potential
for systemic toxicity and should be used according to guidelines and with
increased vigilance and prudent monitoring in patients at increased risk for
nephrotoxicity.
PMID- 17032908
TI - Pulmonary abnormalities in immunocompromised patients: comparative detection with
parallel acquisition MR imaging and thin-section helical CT.
AB - PURPOSE: To compare parallel acquisition magnetic resonance (MR) imaging with
thin-section helical computed tomography (CT) for depiction of pulmonary
abnormalities suggestive of pneumonia in immunocompromised patients. MATERIALS
AND METHODS: The institutional review board approved this study; prior consent
was obtained. Thirty consecutive neutropenic patients (10 women, 20 men; mean
age, 51 years +/- 15 [standard deviation]; range, 25-75 years) with fever of
unknown origin or clinical signs and symptoms of lung infection were examined
with breath-hold single-shot half-Fourier turbo spin-echo MR imaging. To reduce
image blurring and increase MR signal in the lungs, the echo time was shortened
with generalized autocalibrating partially parallel acquisition (GRAPPA).
Patients underwent thoracic CT (four detector rows and 1-mm section thickness [4
x 1 mm]; pitch, 6) as reference standard. Pulmonary abnormalities (ill-defined
nodules, ground-glass opacity areas, and consolidation), their location and
distribution, and lesion characteristics were analyzed at MR imaging by three
readers, blinded to results of CT, in consensus. Frequencies were calculated for
each feature; paired Wilcoxon rank sum test was used to examine whether
differences between CT and MR imaging features were statistically significant
(alpha < .05). Bonferroni adjustments were performed. Overall sensitivity,
specificity, and positive and negative predictive values were determined.
RESULTS: Twenty-two patients had pulmonary abnormalities at CT. In 21 (95%)
patients, pneumonia was correctly diagnosed with MR imaging. One false-negative
finding occurred in a patient with ill-defined nodules smaller than 1 cm at CT.
One false-positive finding with MR imaging was the result of blurring and
respiratory artifacts (sensitivity, 95%; specificity, 88%; positive predictive
value, 95%; negative predictive value, 88%). There was no significant difference
in lesion location and distribution. CONCLUSION: With parallel imaging (GRAPPA
technique) and fast MR imaging, detection of pulmonary abnormalities is almost as
good as with CT. MR imaging has a slight disadvantage in its lower capability to
assist in characterization of specific internal features, such as cavitations.
PMID- 17032909
TI - Multidetector CT in abdominal aortic aneurysm treated with endovascular repair:
are unenhanced and delayed phase enhanced images effective for endoleak
detection?
AB - PURPOSE: To retrospectively determine the sensitivity and specificity of
unenhanced, delayed enhanced phase (DEP), and arterial enhanced phase (AEP) multi
detector row computed tomography (CT) for depicting endoleaks during follow-up of
endovascular aneurysm repair. MATERIALS AND METHODS: Fifty patients (two women,
48 men; mean age, 72 years) underwent follow-up multi-detector row CT 1, 6, and
12 months after endovascular aneurysm repair. Unenhanced CT was performed with
2.5-mm collimation; 1-mm collimation was used with AEP and DEP examinations. Two
independent readers assessed the presence of endoleak in three reading sessions:
AEP (session A), unenhanced and AEP (session B), and AEP and DEP (session C). At
6- and 12-month follow-up, a fourth set was included: 1-month unenhanced and AEP
(session D). Sensitivity, specificity, and positive predictive value of each
session were calculated. Triple-phase multi-detector row CT was the reference
standard. RESULTS: At 1 month, sensitivity, specificity, and positive predictive
value, respectively, were 79%, 75%, and 55% for session A; 93%, 97%, and 93% for
session B; and 93%, 78%, and 62% for session C. At 6 months, sensitivity,
specificity, and positive predictive value, respectively, were 92%, 68%, and 48%
for session A; 92%, 100%, and 100% for session B; and 100%, 84%, and 67% for
session C. At 12 months, sensitivity, specificity, and positive predictive value,
respectively, were 80%, 80%, and 50% for session A; 90%, 98%, and 90% for session
B; and 100%, 80%, and 56% for session C. Sensitivity did not significantly differ
(P > .05) among reading sessions A, B, and C, whereas specificity and positive
predictive values in session B were significantly higher (P < .001). For 6- and
12-month follow-up, no significant differences (P > .05) were found between
sessions D and B. CONCLUSION: The combination of AEP and unenhanced imaging
performed at 1-month follow-up offers improved specificity and positive
predictive values compared with AEP alone. DEP imaging does not significantly
increase sensitivity for detection of endoleaks, but it does depict low-flow
endoleaks not seen at AEP.
PMID- 17032910
TI - Malignant astrocytic tumors: clinical importance of apparent diffusion
coefficient in prediction of grade and prognosis.
AB - PURPOSE: To retrospectively assess the apparent diffusion coefficient (ADC) for
prediction of malignancy and prognosis of malignant astrocytic tumors. MATERIALS
AND METHODS: The institutional review board approved this study and did not
require patient informed consent. Findings from 37 consecutive patients (21 men,
16 women; mean age, 43 years) with pathologically proved malignant astrocytic
tumors that included 22 glioblastomas (GBMs) and 15 anaplastic astrocytomas (AAs)
were retrospectively evaluated. The minimum ADC value of each tumor was
preoperatively determined from several regions of interest defined in the tumor,
preferably with avoidance of cystic or necrotic components, on ADC maps derived
from isotropic diffusion-weighted images. Surgical intervention, followed by
radiation therapy, was undertaken in all cases according to hospital protocol.
Immunohistologically, Ki-67 labeling index (LI), indicating cell proliferation,
was also determined. The patients were classified into two groups, progressive
and stable, according to the 2-year observation after the initial treatment.
Correlation analysis (Pearson product moment correlation), Student t test, Welch
test, receiver operating characteristic analysis, and Kaplan-Meier method with
log-rank test were used for statistical evaluation. RESULTS: There was a
significant negative correlation between minimum ADC and Ki-67 LI (r = -0.562, P
< .001). The mean minimum ADC (0.834 x 10(-3) mm2 x sec(-1)) of GBM was
significantly lower than that (1.06 x 10(-3) mm2 x sec(-1)) of AA (P < .001,
Student t test). The mean minimum ADC (0.80 x 10(-3) mm2 x sec(-1)) of the
progressive group was significantly lower than that (1.037 x 10(-3) mm2 x sec(
1)) of the stable group (P < .001). The cutoff value of 0.90 x 10(-3) mm2 x sec(
1) for minimum ADC for differentiation of patients with a favorable prognosis
from those with a poor prognosis provided the best combination of sensitivity
(79%) and specificity (81%) (receiver operating characteristic analysis). The
significant difference in the prognosis between two groups classified by using
this cutoff value of minimum ADC was noted (P = .002, log-rank test). CONCLUSION:
The minimum ADC of malignant astrocytomas can provide additional information
about their clinical malignancy related to posttreatment prognosis.
PMID- 17032911
TI - Active Crohn disease: CT findings and interobserver agreement for enteric phase
CT enterography.
AB - PURPOSE: To retrospectively evaluate small-bowel enhancement characteristics and
the sensitivity, specificity, and interobserver agreement of computed tomographic
(CT) findings by using histologic and endoscopic results as a reference standard
in patients undergoing enteric phase CT enterography. MATERIALS AND METHODS: The
institutional review board approved this retrospective HIPAA-compliant study,
which included patients who consented to having their medical records used for
research purposes. Enteric phase CT enterographic and ileoscopic findings with or
without ileal histologic results were examined in 42 patients (24 women, 18 men).
Enteric phase CT enterography was performed after 150 mL of intravenous contrast
material was administered at 4 mL/sec, with a 45-second delay. Mural attenuation
was measured in the distended and collapsed jejunal and ileal loops and in the
terminal ileum. Two radiologists examined CT images for findings of Crohn
disease. Mural attenuation for different bowel loops was compared by using a
Student t test, with kappa statistics used to measure interobserver agreement and
Pearson correleation coefficients used to compare visual and quantitative
measures. RESULTS: Distended jejunal loops had significantly greater attenuation
than distended ileal loops (113 HU vs 72 HU; P < .001). Attenuation of collapsed
jejunal (134 HU) and ileal (108 HU) loops was greater than that of distended
jejunal and ileal loops (P < .001). Terminal ileal enhancement was the most
sensitive visual CT finding of Crohn disease for both radiologists. Mural
thickening demonstrated the greatest interobserver agreement (kappa = 0.83).
Visual enhancement and quantitative mural attenuation were significantly
correlated (P < .003). CONCLUSION: At enteric phase CT enterography, jejunal
attenuation is greater than ileal attenuation and collapsed bowel loops
demonstrate greater attenuation than distended bowel loops. Mural
hyperenhancement and increased mural thickness are the most sensitive CT findings
of active Crohn disease.
PMID- 17032912
TI - Phyllodes tumor of the breast: correlation between MR findings and histologic
grade.
AB - PURPOSE: To retrospectively evaluate the magnetic resonance (MR) imaging findings
of phyllodes tumor of the breast and to compare these findings with the
histologic grade. MATERIALS AND METHODS: Institutional review board approval and
informed consent were obtained. The authors reviewed the MR findings in 30 female
patients aged 16-73 years (mean, 40.2 years) with surgically confirmed phyllodes
tumors. Analyzed MR findings included tumor shape, margin, internal enhancement,
and size; signal intensity (SI) of tumor higher than that of normal breast tissue
on T1-weighted images; SI of tumor lower than or equal to that of normal tissue
on T2-weighted images; cyst wall appearance; kinetic curve assessment; and
apparent diffusion coefficient (ADC). The MR findings and histologic grade were
statistically analyzed to determine whether any correlations existed. Significant
MR findings were compared with histopathologic findings. RESULTS: Nineteen
benign, six intermediate (characterized by five to nine cell reproductions at 10
high-power fields, pushing or infiltrative margins, moderate stromal cellularity,
and atypia and overgrowth), and five malignant phyllodes tumors were assessed.
Irregular cyst wall (P = .003), tumor SI lower than or equal to normal tissue SI
on T2-weighted images (P = .005), and low ADC (P = .001) correlated significantly
with histologic grade. Tumor SI higher than normal tissue SI on T1-weighted
images was more frequent in the malignant (in three of five tumors) and
intermediate (in three of six tumors) groups than in the benign group (in two of
19 tumors); however, it was not a significant finding (P = .024). Tumor SI higher
than normal tissue SI on T1-weighted images and irregular cyst wall corresponded
histopathologically to hemorrhagic infarction and necrosis, respectively. Tumor
SI lower than or equal to normal tissue SI on T2-weighted images and low ADC
corresponded histopathologically to stromal hypercellularity. Other findings were
not significant. CONCLUSION: Several MR findings can be used to help determine
the histologic grade of phyllodes breast tumors.
PMID- 17032913
TI - Cervical lymph node metastases: MR imaging of gadofluorine M and monocrystalline
iron oxide nanoparticle-47 in a rabbit model of head and neck cancer.
AB - PURPOSE: To prospectively compare the accuracy of gadofluorine M with that of
monocrystalline iron oxide nanoparticle (MION)-47 for the depiction of cervical
lymph node metastases at magnetic resonance (MR) imaging in a rabbit model of
head and neck cancer by using histologic analysis as the reference standard.
MATERIALS AND METHODS: Experiments were approved by the animal care committee.
VX2 carcinomas were implanted in both ears of 11 rabbits 4 weeks before MR
imaging. T2-weighted, T2*-weighted, and T1-weighted MR images were acquired, and
sequential T1-weighted MR imaging was performed immediately and 30 minutes after
administration of gadofluorine M (0.05 mmol gadolinium per kilogram body weight).
T2-weighted and T2*-weighted MR imaging were performed 24 hours after
administration of MION-47 (2.6 mg iron per kilogram body weight). Gadofluorine M-
and MION-47-enhanced MR imaging were performed separately and independently by
two radiologists who had no knowledge of histopathologic results, and the
presence of metastases in lymph nodes was evaluated. A receiver operating
characteristic analysis was conducted to compare the diagnostic value of
gadofluorine M- and MION-47-enhanced MR imaging. RESULTS: Metastases were
confirmed in 20 of 77 lymph nodes at histopathologic analysis. The area under the
curve was significantly greater for gadofluorine M-enhanced MR imaging (0.997 and
0.981 for readers 1 and 2, respectively) than for MION-47-enhanced MR imaging
(0.889 and 0.846 for readers 1 and 2, respectively). For gadofluorine M-enhanced
MR imaging, sensitivity was 100% for both readers and specificity was 89.5% for
reader 1 and 87.7% for reader 2. For MION-47-enhanced MR imaging, sensitivity was
80.0% for both readers and specificity was 75.4% for reader 1 and 71.9% for
reader 2. CONCLUSION: Gadofluorine M-enhanced MR imaging has higher accuracy for
depicting lymph node metastases than does MION-47-enhanced MR imaging.
PMID- 17032914
TI - High-spatial-resolution multistation MR angiography with parallel imaging and
blood pool contrast agent: initial experience.
AB - The purpose of this study was to prospectively evaluate the diagnostic accuracy
of reader detection of 75% or greater stenosis at high-spatial-resolution
multistation magnetic resonance (MR) angiography performed with matrix coils and
a blood pool contrast agent. Ten healthy volunteers and 10 patients were
examined. All participants provided informed consent to participate in this
institutional review board-approved study. For contrast agent-enhanced
multistation MR angiography, an albumin-binding gadolinium chelate, gadofosveset
trisodium, was used. Imaging was performed during the first-pass and steady-state
phases of the contrast agent. Vessel conspicuity on the first-pass MR angiograms
obtained in both volunteers and patients was rated as excellent for 93% of
vessels. At steady-state imaging, vessel conspicuity was rated as excellent or
good for 89% of vessels. Gadofosveset trisodium-enhanced MR angiography yielded
sensitivities of 100% and 97% and specificities of 96% and 97% for detection of
significant disease in the carotid and lower extremity arteries, respectively.
PMID- 17032915
TI - Donor-derived thymic-dependent T cells cause chronic graft-versus-host disease.
AB - Chronic graft-versus-host disease (GVHD) is the most common cause of poor long
term outcomes after allogeneic bone marrow transplantation (BMT), but the
pathophysiology of chronic GVHD still remains poorly understood. We tested the
hypothesis that the impaired thymic negative selection of the recipients will
permit the emergence of pathogenic T cells that cause chronic GVHD. Lethally
irradiated C3H/HeN (H-2k) recipients were reconstituted with T-cell-depleted bone
marrow cells from major histocompatibility complex [MHC] class II-deficient (H2
Ab1-/-) B6 (H-2b) mice. These mice developed diseases that showed all of the
clinical and histopathological features of human chronic GVHD. Thymectomy
prevented chronic GVHD, thus confirming the causal association of the thymus.
CD4+ T cells isolated from chronic GVHD mice were primarily donor reactive, and
adoptive transfer of CD4+ T cells generated in these mice caused chronic GVHD in
C3H/HeN mice in the presence of B6-derived antigen-presenting cells. Our results
demonstrate for the first time that T cells that escape from negative thymic
selection could cause chronic GVHD after allogeneic BMT. These results also
suggest that self-reactivity of donor T cells plays a role in this chronic GVHD,
and improvement in the thymic function may have a potential to decrease chronic
GVHD.
PMID- 17032916
TI - New agents that stimulate erythropoiesis.
AB - Recombinant human erythropoietin (rhEpo) has proven to be remarkably safe and
effective for treatment of anemias, primarily those secondary to renal disease
and malignancy. Despite the worldwide use of rhEpo, concerns about its cost, the
need for frequent parenteral administration, and the development of anti-Epo
antibodies have prompted development of improved agents to stimulate
erythropoiesis. Three strategies appear to be particularly promising. The half
life of Epo in the circulation can be prolonged by the addition of N-linked
carbohydrate groups, by formation of adducts with polyethylene glycol, and by
preparation of Epo multimers. Second, mimetic peptides can effectively trigger
signal transduction at the Epo receptor, thereby boosting red-cell production.
Finally, the hypoxia inducible transcription factor (HIF) can be
pharmacologically induced by oral agents, resulting in enhanced expression not
only of endogenous Epo but also of other genes important in the regulation of
erythropoiesis.
PMID- 17032917
TI - MCP-1 mediates TGF-beta-induced angiogenesis by stimulating vascular smooth
muscle cell migration.
AB - Transforming growth factor-beta (TGF-beta) and its signaling mediators play
crucial roles in vascular formation. Our previous microarray analysis identified
monocyte chemoattractant protein-1 (MCP-1) as a TGF-beta target gene in
endothelial cells (ECs). Here, we report that MCP-1 mediates the angiogenic
effect of TGF-beta by recruiting vascular smooth muscle cells (VSMCs) and
mesenchymal cells toward ECs. By using a chick chorioallantoic membrane assay, we
show that TGF-beta promotes the formation of new blood vessels and this promotion
is attenuated when MCP-1 activity is blocked by its neutralizing antibody. Wound
healing and transwell assays established that MCP-1 functions as a
chemoattractant to stimulate migration of VSMCs and mesenchymal 10T1/2 cells
toward ECs. Furthermore, the conditioned media from TGF-beta-treated ECs
stimulate VSMC migration, and inhibition of MCP-1 activity attenuates TGF-beta
induced VSMC migration toward ECs. Finally, we found that MCP-1 is a direct gene
target of TGF-beta via Smad3/4. Taken together, our findings suggest that MCP-1
mediates TGF-beta-stimulated angiogenesis by enhancing migration of mural cells
toward ECs and thus promoting the maturation of new blood vessels.
PMID- 17032918
TI - GSK-3 mediates differentiation and activation of proinflammatory dendritic cells.
AB - The key components of the intracellular molecular network required for the
expression of a specific function of dendritic cells (DCs) are as yet undefined.
Using an in vitro model of human monocyte-derived DC differentiation, this study
investigates the role of glycogen synthase kinase 3 (GSK-3), a multifunctional
enzyme critical for cellular differentiation, apoptosis, self-renewal, and
motility, in this context. We demonstrate that GSK-3 (1) inhibits macrophage
development during differentiation of DCs, (2) is constitutively active in
immature DCs and suppresses spontaneous maturation, and (3) acquires a
proinflammatory functional status mediating high levels of IL-12, IL-6, and TNF
alpha secretion, and partially inhibits IL-10 in the context of DC activation. In
particular, GSK-3 enhances IL-12p35 mRNA expression and thus the production of
the proinflammatory cytokine IL-12p70 by integrating the activities of other
kinases priming GSK-3 targets and the inhibitory effects of Akt-1. GSK-3 may
therefore act as a key integrator of activating and inhibitory pathways involved
in proinflammatory DC differentiation and activation.
PMID- 17032919
TI - Plasminogen activator inhibitor type 1 is protective during severe Gram-negative
pneumonia.
AB - Plasminogen activator inhibitor type-1 (PAI-1) levels are consistently elevated
in patients with severe pneumonia and sepsis and highly predictive for an
unfavorable outcome. In addition, pneumonia is associated with strongly elevated
PAI-1 levels in the pulmonary compartment. However, whether PAI-1 causally
affects antibacterial host defense in vivo remains unknown. We report here that
pneumonia caused by the common respiratory pathogen Klebsiella pneumoniae is
associated with local production of PAI-1 in the lungs of wild-type mice. PAI-1
deficiency impaired host defense as reflected by enhanced lethality and increased
bacterial growth and dissemination in mice with a targeted deletion of the PAI-1
gene. Conversely, transgenic overexpression of PAI-1 in the lung using a
replication-defective adenoviral vector markedly improved host defense against
Klebsiella pneumonia and sepsis. PAI-1 deficiency reduced accumulation of
neutrophils in the lungs during pneumonia, whereas PAI-1 overexpression in
healthy lungs resulted in neutrophil influx, suggesting that PAI-1 protects the
host against Klebsiella pneumonia by promoting neutrophil recruitment to the
pulmonary compartment. These data demonstrate for the first time that PAI-1 is
essential for host defense against severe Gram-negative pneumonia.
PMID- 17032920
TI - VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor
metastasis to distant sites.
AB - The mechanisms by which tumors metastasize to sentinel and distant lymph nodes,
and beyond, are poorly understood. We developed transgenic mice that overexpress
vascular endothelial growth factor-C (VEGF-C) and green fluorescent protein
specifically in the skin and studied the effects of chemically-induced skin
carcinogenesis in this model. We found that in contrast to VEGF-A, VEGF-C does
not increase the growth of primary tumors, but instead induces expansion of
lymphatic networks within sentinel lymph nodes, even before the onset of
metastasis. Once the metastatic cells arrived at the sentinel lymph nodes, the
extent of lymphangiogenesis at these sites increased. Of importance, in mice with
metastasis-containing sentinel lymph nodes, tumors that expressed VEGF-C were
more likely to metastasize to additional organs, such as distal lymph nodes and
lungs. No metastases were observed in distant organs in the absence of lymph node
metastases. These findings indicate an important role of VEGF-C-induced lymph
node lymphangiogenesis in the promotion of cancer metastasis beyond the sentinel
lymph nodes. VEGF-C is therefore a good target to slow or even prevent the onset
of metastasis.
PMID- 17032921
TI - Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC
UKALL12/ECOG 2993 study.
AB - Most adults with acute lymphoblastic leukemia (ALL) who achieve complete
remission (CR) will relapse. We examined the outcome of 609 adults with recurring
ALL, all of whom were previously treated on the Medical Research Council (MRC)
UKALL12/ECOG2993 study, where the overall survival (OS) of newly diagnosed
patients is 38% (95% confidence interval [CI]=36%-41%) at 5 years. By contrast,
OS at 5 years after relapse was 7% (95% CI=4%-9%). Factors predicting a good
outcome after salvage therapy were young age (OS of 12% in patients younger than
20 years vs OS of 3% in patients older than 50 years; 2P<.001) and short duration
of first remission (CR1) (OS of 11% in those with a CR1 of more than 2 years
versus OS of 5% in those with a CR1 of less than 2 years; 2P<.001). Treatment
received in CR1 did not influence outcome after relapse. In a very highly
selected subgroup of patients who were able to receive HSCT after relapse, some
were long-term survivors. We conclude from a large, unselected series with mature
follow-up that most adults with recurring ALL, whatever their prior treatment,
cannot be rescued using currently available therapies. Prevention of recurrence
is the best strategy for long-term survival in this disease.
PMID- 17032922
TI - PKC412 demonstrates JNK-dependent activity against human multiple myeloma cells.
AB - The effect and mode of action of the protein kinase C (PKC) inhibitor PKC412 on
human multiple myeloma (MM) cell lines (HMCLs) and primary MM cells was explored.
We found that PKC412 induced apoptosis of HMCLs and primary MM cells with
variable efficacy; however, some activity was seen against all HMCLs and primary
MM cells with at least 0.5 microM PKC412. PARP cleavage and decreased PKC
activity was observed in all HMCLs tested. Furthermore, PKC412 inhibited C-FOS
transcription and nuclear protein expression, induced reactive oxygen species
(ROS) production, and induced both sustained C-JUN expression and
phosphorylation. The latter was inhibited by cotreatment with the JNK inhibitor
SP600125, which similarly abrogated PKC412-induced apoptosis, suggesting that
PKC412-induced apoptosis is a JNK-dependent event. PKC412 treatment secondarily
induced prosurvival stress responses as evidenced by activation of NFkappaB and
increased expression of the heat shock proteins HSP70 and HSP90. Consistent with
the former, sequential inhibition of NFkappaB activation with bortezomib or SN50
synergistically enhanced cell killing. Our results demonstrate that PKC412
induces JNK-dependent apoptosis of HMCLs and primary MM cells and that this
effect is enhanced by NFkappaB inhibition. The further evaluation of PKC412 in
the treatment of MM is justified.
PMID- 17032923
TI - Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts
for studying megakaryocyte and platelet function in vivo.
AB - To generate transgenic mice that express Cre-recombinase exclusively in the
megakaryocytic lineage, we modified a mouse bacterial artificial chromosome (BAC)
clone by homologous recombination and replaced the first exon of the platelet
factor 4 (Pf4), also called CXCL4, with a codon-improved Cre cDNA. Several
strains expressing the transgene were obtained and one strain, Q3, was studied in
detail. Crossing Q3 mice with the ROSA26-lacZ reporter strain showed that Cre
recombinase activity was confined to megakaryocytes. These results were further
verified by crossing the Q3 mice with a strain containing loxP-flanked integrin
beta1. Excision of this conditional allele in megakaryocytes was complete at the
DNA level, and platelets were virtually devoid of the integrin beta1 protein. The
Pf4-Cre transgenic strain will be a valuable tool to study megakaryopoiesis,
platelet formation, and platelet function.
PMID- 17032925
TI - Humoral immune response and immunoglobulin G Fc receptor genotype are associated
with better clinical outcome following idiotype vaccination in follicular
lymphoma patients regardless of their response to induction chemotherapy.
AB - We have reported that anti-idiotype antibody response and FcgammaRIIIa 158
valine/valine (V/V) genotype both correlate with better outcome in a group of 136
follicular lymphoma patients receiving idiotype vaccination after induction
chemotherapy. Here, we examined whether this correlation is related in any way to
the chemotherapy response. In patients with complete response (CR), the 5-year
progression-free survival (PFS) was 69% for patients with antibody response
and/or V/V genotype, while the PFS was only 40% for patients with neither; the
median time to progression (TTP) was 10.47 versus 3.46 years (P=.012). In
patients with partial response (PR), the 5-year PFS was 57% for patients with
antibody response and/or V/V genotype, and 17% for patients with neither; the
median TTP was not reached versus 1.31 years (P=.001). This study further
confirms the strong association of clinical outcome with antibody response and
with the functionally more active form of the Fc receptor in patients receiving
idiotype vaccination regardless of their response to induction chemotherapy.
PMID- 17032924
TI - Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM).
AB - Second mitochondria-derived activator of caspases (Smac) promotes apoptosis via
activation of caspases. Here we show that a low-molecular-weight Smac mimetic
LBW242 induces apoptosis in multiple myeloma (MM) cells resistant to conventional
and bortezomib therapies. Examination of purified patient MM cells demonstrated
similar results, without significant cytotoxicity against normal lymphocytes and
bone marrow stromal cells (BMSCs). Importantly, LBW242 abrogates paracrine MM
cell growth triggered by their adherence to BMSCs and overcomes MM cell growth
and drug-resistance conferred by interleukin-6 or insulinlike growth factor-1.
Overexpression of Bcl-2 similarly does not affect LBW242-induced cytotoxicity.
Mechanistic studies show that LBW242-induced apoptosis in MM cells is associated
with activation of caspase-8, caspase-9, and caspase-3, followed by PARP
cleavage. In human MM xenograft mouse models, LBW242 is well tolerated, inhibits
tumor growth, and prolongs survival. Importantly, combining LBW242 with novel
agents, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
or the proteasome inhibitors bortezomib and NPI-0052, as well as with the
conventional anti-MM agent melphalan, induces additive/synergistic anti-MM
activity. Our study therefore provides the rationale for clinical protocols
evaluating LBW242, alone and together with other anti-MM agents, to improve
patient outcome in MM.
PMID- 17032926
TI - The impact of altered p53 dosage on hematopoietic stem cell dynamics during
aging.
AB - A temporal decline in tissue stem cell functionality may be a key component of
mammalian aging. The tumor suppressor p53 has recently been implicated as a
potential regulator of aging. We examined age-associated hematopoietic stem cell
(HSC) dynamics in mice with varying p53 activities. Reduced p53 activity in p53+/
mice was associated with higher numbers of proliferating hematopoietic stem and
progenitor cells in old age compared with aged wild-type (p53+/+) mice. We also
assessed HSC dynamics in a p53 mutant mouse model (p53+/m) with higher apparent
p53 activity than wild-type mice. The p53 hypermorphic (p53+/m) mice display
phenotypes of premature aging. Many aged p53+/m organs exhibit reduced
cellularity and atrophy, suggesting defects in stem-cell regenerative capacity.
HSC numbers from old p53+/m mice fail to increase with age, unlike those of their
p53+/+ and p53+/- counterparts. Moreover, transplantation of 500 HSCs from old
p53+/m mice into lethally irradiated recipients resulted in reduced engraftment
compared with old wild-type p53+/+ and p53+/- HSCs. Thus, alteration of p53
activity affects stem-cell numbers, proliferation potential, and hematopoiesis in
older organisms, supporting a model in which aging is caused in part by a decline
in tissue stem cell regenerative function.
PMID- 17032927
TI - CpG DNA activation and plasma-cell differentiation of CD27- naive human B cells.
AB - Unmethylated CpG DNA activation of naive CD27- B cells has been reported to
require B-cell-receptor (BCR) cross-linking. We describe a culture system using
CpG DNA with sequential steps for T-cell-independent activation of naive
CD19+CD27- human peripheral blood B cells that induces efficient CD138+ plasma
cell differentiation. CD27+ and CD27- B cells were cultured in a 3-step system:
(1) days 0 to 4: CpG, IL-2/10/15; (2) days 4 to 7: IL-2/6/10/15 and anti-CD40L;
(3) days 7 to 10: IL-6/15, IFN-alpha, hepatocyte growth factor, and hyaluronic
acid. Both CD27+ and CD27- B cells up-regulated intracytoplasmic TLR-9 following
CpG DNA activation. CD27- B-cell activation required cell-cell contact. Both
naive and memory B cells progressed to a plasma-cell phenotype:
CD19lowCD20lowCD27+CD38+HLA-DRlow. Seventy percent of the CD27--derived CD138+
cells demonstrated productive V chain rearrangements without somatic mutations,
confirming their origin from naive precursors. Plasma cells derived from CD27+ B
cells were primarily IgG+, while those from CD27- B cells were IgM+. Our results
indicate that under certain conditions, naive B cells increase TLR-9 expression
and proliferate to CpG DNA stimulation without BCR signaling. In addition to its
immunologic significance, this system should be a valuable method to interrogate
the antigenic specificity of naive B cells.
PMID- 17032928
TI - Testosterone production in mice lacking inducible nitric oxide synthase
expression is sensitive to restraint stress.
AB - Immobilization stress (IMO) induces a rapid increase in glucocorticoid secretion
[in rodents, corticosterone CORT)] and this is associated with decreased
circulating testosterone (T) levels. Nitric oxide (NO), a reactive free radical
and neurotransmitter, has been reported to be produced at higher rates in tissues
such as brain during stress. The biosynthesis of T is also known to be
dramatically suppressed by NO. Specifically, the inducible isoform of nitric
oxide synthase (iNOS) was directly implicated in this suppression. To assess the
respective roles of CORT and NO in stress-mediated inhibition of T production,
adult wild-type (WT) and inducible nitric oxide synthase knockout (iNOS(-/-))
male mice were evaluated. Animals of each genotype were assigned to either basal
control or 3-h IMO groups. Basal plasma and testicular T levels were equivalent
in both genotypes, whereas testicular weights of mutant mice were significantly
higher compared with WT animals. Exposure to 3-h IMO increased plasma CORT and
decreased T concentrations in mice of both genotypes. Testicular T levels were
also affected by stress in WT and mutant males, being sharply reduced in both
genotypes. However, the concentrations of nitrite and nitrate, the stable
metabolites of NO measured in testicular extracts, did not differ between control
and stressed WT and iNOS(-/-) mice. These results support the hypothesis that
CORT, but not NO, is a plausible candidate to mediate rapid stress-induced
suppression of Leydig cell steroidogenesis.
PMID- 17032929
TI - Effects of transient PTH on early proliferation, apoptosis, and subsequent
differentiation of osteoblast in primary osteoblast cultures.
AB - In primary calvarial osteoblast cultures derived from transgenic mice expressing
green fluorescent protein (GFP) under the control of 3.6-kb Col1a1 promoter, the
emergence of GFP signal marks the transition of multipotential osteoprogenitors
into preosteoblasts. Early transient treatment (days 1-7) of these cultures with
parathyroid hormone (PTH) has an anabolic effect that is not associated with an
increase in total DNA content or cell number in day 21 cultures. In the present
study, the effect of early PTH treatment on cell proliferation and apoptosis was
examined in greater detail in GFP(+) and GFP(-) cells using flow cytometry. In
preconfluent cultures, PTH significantly reduced the proportion of cells in S
phase but increased those in G(0)/G(1) and G(2)+M phases in both GFP(+) and GFP(
) subpopulations. PTH decreased apoptosis only in GFP(-) but not GFP(+) cells,
indicating an increased survival of GFP(-) cells. In contrast, PTH did not change
the amounts of cell proliferation and apoptosis seen in either compartment after
these cultures reached confluence. To further assess the effect of early PTH
treatment on osteogenic differentiation, secondary cultures of sorted GFP(+) or
GFP(-) cells were obtained from day 7 primary cultures that had been treated for
1 wk with PTH. This treatment resulted in larger areas of GFP expression
accompanied by increased xylenol orange/von Kossa staining in the secondary
cultures of GFP fractions. Early transient PTH treatment appears to enhance the
commitment of progenitor cells to an osteogenic fate and results in a higher
proportion of cells that achieve full osteoblast differentiation.
PMID- 17032930
TI - Risk of venous thromboembolism among hospitalized medically ill patients.
AB - PURPOSE: The 90-day risk of venous thromboembolism (VTE) among medically ill
patients admitted to a hospital was estimated and is discussed. SUMMARY: Patients
aged > or =40 years who were hospitalized between January 1, 1998, and June 30,
2002, for reasons other than traumatic injury, labor and delivery, mental
disorder, or VTE and who did not undergo surgery were identified in a large U.S.
healthcare claims database. Patients receiving anticoagulants in the 90-day
period preceding hospital admission were excluded. We estimated the percentage of
study subjects who developed clinical deep-vein thrombosis (DVT) or pulmonary
embolism (PE) within 90 days of hospital admission using Kaplan-Meier methods. We
also estimated hazard ratios (HRs) for potential risk factors for VTE using
univariate and stepwise multivariate Cox proportional hazards regression models.
Among 92,162 study subjects, 1468 (1.59%) developed clinical DVT or PE within 90
days of hospital admission; 18% of these events occurred postdischarge. In
multivariate analyses, significant risk factors for clinical VTE included: 1)
history of cancer (HR, 1.67; 95% confidence interval [CI], 1.45-1.93); 2) history
of VTE within six months of index admission (HR, 6.14; 95% CI, 4.74-7.96); 3)
operating room procedure within 30 days of index admission (HR, 1.81; 95% CI,
1.47-2.24); 4) peripheral artery disease during index admission (HR, 1.68; 95%
CI, 1.28-2.21); and 5) heart failure during index admission (HR, 1.72; 95% CI,
1.52-1.95). CONCLUSION: The risk of clinical VTE among medically ill patients
admitted to a hospital, although less than that of patients undergoing major
surgery, is not negligible. Patients with a history of recent VTE or surgery,
those who are admitted to the intensive care unit, those with an admitting
diagnosis of heart failure, and those with active cancer are at especially high
risk of VTE and deserve increased consideration for prophylaxis.
PMID- 17032931
TI - Thromboprophylaxis in medically ill patients at risk for venous thromboembolism.
AB - PURPOSE: According to guidelines from the American College of Chest Physicians,
low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) should be
prescribed to medical (nonsurgical) patients at high risk of venous
thromboembolism. Thromboprophylaxis and mortality rates were determined in
medical inpatients with indications for thromboprophylaxis. Cost differences
between patient groups were investigated and are discussed. SUMMARY: Using
Solucient's ACTracker Inpatient Database, medical discharges between January 2001
and December 2004 were extracted and patients who had indications for
thromboprophylaxis (acute myocardial infarction, ischemic stroke, cancer, heart
failure, or severe lung disease) were identified. Patients < 40 years or with
deep-vein thrombosis or pulmonary embolism, active peptic ulcer, malignant
hypertension, blood disease, HIV infection, or intubation of gastrointestinal or
respiratory tract were excluded. Rates of thromboprophylaxis and mortality were
compared between groups. Mean total drug costs and hospital costs per patient
discharge were compared between patient groups. Of 12,887,080 medical discharges
extracted from 330 hospitals, there were 2,367,362 patients with indications for
thromboprophylaxis. Patients were subdivided on the basis of whether they
received thromboprophylaxis (n = 717,850) or not (n = 1,649,512). The
thromboprophylaxis rate was low, despite increasing from 26% to 33% over the
study period. Patients receiving thromboprophylaxis had significantly lower risk
adjusted mortality rates than those who did not (p < 0.001), except those with
ischemic stroke. The mean total drug cost per patient receiving LMWH and UFH
($791 and $569, respectively) was higher than for patients not receiving
thromboprophylaxis ($372) (p < 0.001). The mean total hospital cost per patient
receiving UFH ($7615) was higher than for LMWH ($6866, p < 0.001). CONCLUSION:
The thromboprophylaxis rate among medical patients was low, with no significant
improvement between 2001 and 2004. Thromboprophylaxis can impact patient
mortality rates. Economic evaluation revealed that the use of LMWH for
thromboprophylaxis in at-risk medical patients was associated with higher total
drug costs but lower total hospital costs than UFH. Efforts should be made to
increase clinicians' awareness of clinical guidelines.
PMID- 17032932
TI - Prevention of venous thromboembolism: clinical and economic implications.
Introduction.
PMID- 17032933
TI - Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic
syndrome.
AB - PURPOSE: Deep-vein thrombosis (DVT) and pulmonary embolism (PE) are associated
with major morbidity and mortality, with their burden often extending to longer
term complications such as event recurrence and post-thrombotic syndrome (PTS).
Few data exist on the overall economic burden of DVT and PE and their sequelae. A
retrospective observational cohort study was conducted to determine the direct
medical costs of a DVT or PE patient across the entire continuum of care.
SUMMARY: Administrative claims data for patients with a DVT or PE diagnosis (ICD
9-CM code) and patients with possible evidence of PTS between January 1, 1997,
and March 31, 2004, were extracted from the PharMetrics Patient-Centric Database,
which comprises fully adjudicated medical and pharmaceutical claims for U.S.
health care-plan enrollees. Resource utilization and annualized direct medical
costs of care for patients with DVT and/or PE were calculated and compared with
matched controls. A total of 26,958 patients met the study inclusion criteria. Of
the 17,634 patients evaluable for the PTS cohort, 663 (3.8%) patients experienced
PTS. Patients with DVT, PE, or DVT and PE had higher annualized direct medical
costs before the index (initial) DVT and/or PE event (median: $7227, $6381, and
$6771, respectively) than controls (median: $1045). During and after the DVT/PE
event, annualized median costs rose to $17,512, $18,901, and $25,554,
respectively, compared with $680 in the control group. Annualized median total
costs for the PTS group were $20,569 compared with $15,843 in matched controls
with DVT and/or PE and no PTS. CONCLUSION: These data suggest that the initial
acute DVT or PE event is associated with high total health care costs and that
these costs are further increased by subsequent events such as recurrent DVT or
PE and PTS. Early detection and appropriate treatment of this high-risk
population have the potential for both clinical and economic benefits.
PMID- 17032934
TI - A model of nitric oxide tubulovascular cross talk in a renal outer medullary
cross section.
AB - We developed a two-dimensional model of NO transport in a cross section of the
inner stripe (IS) of the rat outer medulla to determine whether tubular and
vascular generation of NO result in significant NO concentration (C(NO))
differences between the periphery and the center of vascular bundles and thereby
affect medullary blood flow distribution. Following the approach of Layton and
Layton (Layton AT, Layton HE. Am J Physiol Renal Physiol 289: F1346-F1366, 2006),
the structural heterogeneity of the IS was incorporated in a representative unit
consisting of four concentric regions centered on a vascular bundle. Our model
suggests that the diffusion distance of NO in the interstitium is limited to a
few micrometers. We predict that, under basal conditions, epithelial NO
generation raises the average C(NO) in pericytes surrounding peripheral
descending vasa recta (DVR) by a few nanomoles relative to that in pericytes
surrounding central DVR. The short descending limbs and long ascending limbs are
found to exert the greatest effect on C(NO) in pericytes; long descending limbs
and short ascending limbs only have a moderate effect, whereas outer medullary
collecting ducts, which are situated far from the vascular bundle center, do not
affect pericyte C(NO). Our results suggest that selective stimulation of
epithelial NO production should significantly raise the periphery-to-center DVR
diameter ratio, thereby increasing the outer medulla-to-inner medulla blood flow
ratio. However, concomitant increases in epithelial superoxide (O(2)(-))
production would counteract this effect. This model confirms the importance of NO
and O(2)(-) interactions in mediating tubulovascular cross talk.
PMID- 17032935
TI - New insights into the regulation of V-ATPase-dependent proton secretion.
AB - The vacuolar H(+)-ATPase (V-ATPase) is a key player in several aspects of
cellular function, including acidification of intracellular organelles and
regulation of extracellular pH. In specialized cells of the kidney, male
reproductive tract and osteoclasts, proton secretion via the V-ATPase represents
a major process for the regulation of systemic acid/base status, sperm maturation
and bone resorption, respectively. These processes are regulated via modulation
of the plasma membrane expression and activity of the V-ATPase. The present
review describes selected aspects of V-ATPase regulation, including recycling of
V-ATPase-containing vesicles to and from the plasma membrane,
assembly/disassembly of the two domains (V(0) and V(1)) of the holoenzyme, and
the coupling ratio between ATP hydrolysis and proton pumping. Modulation of the V
ATPase-rich cell phenotype and the pathophysiology of the V-ATPase in humans and
experimental animals are also discussed.
PMID- 17032936
TI - Endotoxin and cisplatin synergistically stimulate TNF-alpha production by renal
epithelial cells.
AB - Acute renal failure often occurs in the clinical setting of multiple renal
insults. Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the
pathogenesis of cisplatin nephrotoxicity, ischemia-reperfusion injury, and
endotoxin-induced acute renal failure. The current studies examined the
interactions between cisplatin and endotoxin with particular emphasis on TNF
alpha production. Treatment of cultured murine proximal tubule cells (TKPTS
cells) with cisplatin resulted in a modest production of TNF-alpha, while
treatment with endotoxin did not result in any TNF-alpha production. However, the
combination of cisplatin and endotoxin resulted in large amounts of TNF-alpha
synthesis and secretion. The stimulation of TNF-alpha production was dependent on
cisplatin-induced activation of p38 MAPK and was associated with phosphorylation
of the translation initiation factor eIF4E and its upstream kinase Mnk1.
Inhibition of p38 MAPK and, to a lesser extent, ERK, reduced cisplatin+endotoxin
stimulated TNF-alpha production and phosphorylation of Mnk1 and eIF4E. Synergy
between cisplatin and endotoxin was also observed in certain tumor cell lines,
but not in macrophages. In macrophages, in contrast to TKPTS cells, endotoxin
alone activated p38 MAPK and stimulated TNF-alpha production with no added impact
by cisplatin. The combination of cisplatin and endotoxin did not result in
synergistic production of other cytokines, e.g., MCP-1 and MIP2, by TKPTS cells.
In summary, these studies indicate that cisplatin sensitizes renal epithelial
cells to endotoxin and dramatically increases the translation of TNF-alpha mRNA
in a p38 MAPK-dependent manner. These interactions between cisplatin and
endotoxin may be relevant to the pathogenesis of cisplatin nephrotoxicity in
humans.
PMID- 17032937
TI - Statin-sensitive endocytosis of albumin by glomerular podocytes.
AB - Glomerular podocytes are critical regulators of glomerular permeability via the
slit diaphragm and may play a role in cleaning the glomerular filter. Whether
podocytes are able to endocytose proteins is uncertain. We studied protein
endocytosis in conditionally immortalized mouse and human podocytes using FITC
albumin by direct quantitative assay and by fluorescence microscopy and electron
microscopy in mouse podocytes. Furthermore, in vivo uptake was studied in human,
rat, and mouse podocytes. Both mouse and human podocytes displayed specific one
site binding for FITC-albumin with K(d) of 0.91 or 0.44 mg/ml and B(max) of 3.15
or 0.81 microg/mg cell protein, respectively. In addition, they showed avid
endocytosis of FITC-albumin with K(m) of 9.48 or 4.5 mg/ml and V(max) of 474.3 or
97.4 microg.mg cell protein(-1).h(-1), respectively. Immunoglobulin and
transferrin were inefficient competitors of this process, indicating some
specificity for albumin. Accumulation of endocytosed albumin could be
demonstrated in intracellular vesicles by fluorescence confocal microscopy and
electron microscopy. Endocytosis was sensitive to pretreatment with simvastatin.
In vivo accumulation of albumin was found in all three species but was most
pronounced in the rat. We conclude that podocytes are able to endocytose protein
in a statin-sensitive manner. This function is likely to be highly significant in
health and disease. In addition, protein endocytosis by podocytes may represent a
useful, measurable phenotypic characteristic against which potentially injurious
or beneficial interventions can be assessed.
PMID- 17032938
TI - Regulation of renal glucose transporters during severe inflammation.
AB - Severe sepsis is accompanied by acute renal failure (ARF) with renal tubular
dysfunction and glucosuria. In this study, we aimed to determine the regulation
of renal tubular glucose transporters during severe experimental inflammation.
Male C57BL/6J mice were injected with LPS or proinflammatory cytokines, and renal
perfusion, glomerular filtration rate (GFR), fractional glucose excretion, and
expression of tubular glucose transporters were determined. We found a decreased
plasma glucose concentration with impaired renal tissue perfusion and GFR and
increased fractional glucose excretion associated with decreased expression of
SGLT2, SGLT3, and GLUT2 after LPS injection. Similar alterations were observed
after application of TNF-alpha, IL-1beta, IL-6, or IFN-gamma. To clarify the role
of proinflammatory cytokines, we performed LPS injections in knockout mice with
deficiencies for TNF-alpha, IL-1 receptor type 1, IFN-gamma, or IL-6 as well as
LPS injections in glucocorticoid-treated wild-type mice. LPS-induced alterations
of glucose transporters also were present in single-cytokine knockout mice. In
contrast, glucocorticoid treatment clearly attenuated LPS-induced changes in
renal glucose transporter expression and improved GFR and fractional glucose
excretion. LPS-induced decrease of renal perfusion was not improved by
glucocorticoids, indicating a minor role of ischemia in the development of septic
renal dysfunction. Our results demonstrate modifications of tubular glucose
transporters during severe inflammation that are probably mediated by
proinflammatory cytokines and account for the development of ARF with increased
fractional glucose excretion. In addition, our findings provide an explanation
why single anti-cytokine strategies fail in the therapy of septic patients and
contribute to an understanding of the beneficial effects of glucocorticoids on
septic renal dysfunction.
PMID- 17032939
TI - Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat.
AB - TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with
subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal
tubule cell (PTC) is responsible for the reabsorption of 5-8 g of glomerular
filtered albumin each day. Excess filtered albumin may contribute to PTC damage
and tubulointerstitial disease. This investigation examined the role of ANG II
induced oxidative stress in PTC structural remodeling: whether such changes could
be modified with in vivo treatment with ANG type 1 receptor (AT(1)R) blockade
(valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6-7 wk old) and age
matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1
mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-beta
D-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and
x60,000 transmission electron microscopy images were used to assess PTC
microvilli structure. There were significant differences in systolic blood
pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and
PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean
diameter of PTC microvilli in the placebo-treated Ren2 rats (P < 0.05) correlated
strongly with albuminuria (r(2) = 0.83) and moderately with MDA (r(2) = 0.49),
and there was an increase in the ratio of abnormal forms of microvilli in placebo
treated Ren2 rats compared with Sprague-Dawley control rats (P < 0.05). AT(1)R
blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-beta-d
glucosaminidase; both therapies corrected abnormalities in oxidative stress and
PTC microvilli remodeling. These data indicate that PTC structural damage in the
Ren2 rat is related to the oxidative stress response to ANG II and/or
albuminuria.
PMID- 17032940
TI - Candesartan prevents long-term impairment of renal function in response to
neonatal partial unilateral ureteral obstruction.
AB - Angiotensin II (ANG II) plays an important role in the development of obstructive
nephropathy. Here, we examined the effects of the ANG II receptor type 1 (AT1R)
blockade using candesartan on long-term renal molecular and functional changes in
response to partial unilateral ureteral obstruction (PUUO). Newborn rats were
subjected to severe PUUO or sham operation (Sham) within the first 48 h of life.
Candesartan was provided in the drinking water (10 mg.kg(-1).day(-1)) from day 21
of life until 10 wk of age. Renal blood flow (RBF) was evaluated by MRI,
glomerular filtration rate (GFR) was measured using the renal clearance of (51)Cr
EDTA, and the renal expression of Na-K-ATPase and the collecting duct water
channel aquaporin-2 (AQP2) was examined by immunoblotting and
immunocytochemistry. At 10 wk of age, PUUO significantly reduced RBF (0.8 +/- 0.1
vs. 1.6 +/- 0.1 ml.min(-1).100 g body wt(-1); P < 0.05) and GFR (37 +/- 16 vs.
448 +/- 111 microl.min(-1).100 g body wt(-1); P < 0.05) compared with Sham.
Candesartan prevented the RBF reduction (PUUO+CAN: 1.6 +/- 0.2 vs. PUUO: 0.8 +/-
0.1 ml.min(-1).100 g body wt(-1); P < 0.05) and attenuated the GFR reduction
(PUUO+CAN: 265 +/- 68 vs. PUUO: 37 +/- 16 microl.min(-1).100 g body wt(-1); P <
0.05). PUUO was also associated with a significant downregulation in the
expression of Na-K-ATPase (75 +/- 12 vs. 100 +/- 5%, P < 0.05) and AQP2 (52 +/-
15 vs. 100 +/- 4%, P < 0.05), which were also prevented by candesartan (Na-K
ATPase: 103 +/- 8 vs. 100 +/- 5% and AQP2: 74 +/- 13 vs. 100 +/- 4%). These
findings were confirmed by immunocytochemistry. Consistent with this, candesartan
treatment partly prevented the reduction in solute free water reabsorption and
attenuated fractional sodium excretion in rats with PUUO. In conclusion,
candesartan prevents or attenuates the reduction in RBF, GFR and dysregulation of
AQP2 and Na-K-ATPase in response to congenital PUUO in rats, suggesting that AT1R
blockade may protect the neonatally obstructed kidney against development of
obstructive nephropathy.
PMID- 17032941
TI - Stanniocalcin-1 regulates endothelial gene expression and modulates
transendothelial migration of leukocytes.
AB - The mammalian counterpart of the fish calcium-regulating hormone stanniocalcin-1
(STC1) inhibits monocyte chemotactic protein-1- and stromal-derived factor-1alpha
(SDF-1alpha)-mediated chemotaxis and diminishes chemokinesis in macrophage-like
RAW264.7 and U937 cells in a manner that may involve attenuation of the
intracellular calcium signal. STC1 is strongly induced in the kidney following
obstructive injury. We hypothesized that STC1 may serve to attenuate the influx
of inflammatory cells to the site of tissue injury. In this study, we examined
the effect of STC1 on the migration of freshly isolated human macrophages,
neutrophils, and T and B lymphocytes through quiescent or IL-1beta-treated human
umbilical vein endothelial cell (HUVEC) monolayers. STC1 inhibited transmigration
of macrophages and T lymphocytes through quiescent or IL-1beta-activated HUVECs
but did not attenuate the transmigration of neutrophils and B lymphocytes. STC1
regulates gene expression in cultured endothelial cells and is detected on the
apical surface of endothelial cells in vivo. The data suggest that STC1 plays a
critical role in transendothelial migration of inflammatory cells and is involved
in the regulation of numerous aspects of endothelial function.
PMID- 17032942
TI - Intravenous bilirubin provides incomplete protection against renal ischemia
reperfusion injury in vivo.
AB - Exogenous bilirubin (BR) substitutes for the protective effects of heme oxygenase
(HO) in several organ systems. Our objective was to investigate the effects of
exogenous BR in an in vivo model of ischemia-reperfusion injury (IRI) in the rat
kidney. Four groups of male Sprague-Dawley rats were anesthetized using
isoflurane in oxygen and treated with 1) 5 mg/kg intravenous (iv) BR, 1 h before
ischemia and 6-h reperfusion; 2) vehicle 1 h before ischemia and 6-h reperfusion;
3) 20 mg/kg iv BR, 1 h before and during ischemia; and 4) vehicle 1 h before and
during ischemia. Bilateral renal clamping (30 min) was followed by 6-h
reperfusion. Infusion of 5 mg/kg iv BR achieved target levels in the serum at 6 h
postischemia (31 +/- 9 micromol/l). Infusion of 20 mg/kg BR reached 50 +/- 22
micromol/l at the end of ischemia, and a significant improvement was seen in
serum creatinine at 6 h (1.07 +/- 28 vs. 1.38 +/- 0.18 mg/dl, P = 0.043).
Glomerular filtration rate, estimated renal plasma flow, fractional excretion of
electrolytes, and renal vascular resistance were not significantly improved in BR
treated groups. Histological grading demonstrated a trend toward preservation of
cortical proximal tubules in rats receiving 20 mg/kg iv BR compared with control;
however, neither BR dose provided protection against injury to the renal medulla.
At the doses administered, iv BR did not provide complete protection against IRI
in vivo. Combined supplementation of both BR and carbon monoxide may be required
to preserve renal blood flow and adequately substitute for the protective effects
of HO in vivo.
PMID- 17032943
TI - Proceedings of the Consensus Conference "The Science of Surge", May 17, 2006, San
Francisco, California, USA.
PMID- 17032944
TI - Current status of surge research.
AB - The dramatic escalation of bioterrorism and public health emergencies in the
United States in recent years unfortunately has coincided with an equally
dramatic decline in the institutions and services we rely on for emergency
preparedness. Hospitals in nearly every metropolitan area in the country have
closed; those that remain open have reduced the number of available beds. "Just
in time" supplies and health professional shortages have further compromised the
nation's overall surge capacity. Emergency departments routinely operate at
capacity. These circumstances make evidence-based research on emergency
preparedness and surge capacity both more urgently needed and more complex. The
Agency for Healthcare Research and Quality and other government and private
agencies have been rapidly widening the field of knowledge in this area in recent
months and years. This report focuses primarily on the work of the Agency for
Healthcare Research and Quality.
PMID- 17032945
TI - Metrics in the science of surge.
AB - Metrics are the driver to positive change toward better patient care. However,
the research into the metrics of the science of surge is incomplete, research
funding is inadequate, and we lack a criterion standard metric for identifying
and quantifying surge capacity. Therefore, a consensus working group was formed
through a "viral invitation" process. With a combination of online discussion
through a group e-mail list and in-person discussion at a breakout session of the
Academic Emergency Medicine 2006 Consensus Conference, "The Science of Surge,"
seven consensus statements were generated. These statements emphasize the
importance of funded research in the area of surge capacity metrics; the utility
of an emergency medicine research registry; the need to make the data available
to clinicians, administrators, public health officials, and internal and external
systems; the importance of real-time data, data standards, and electronic
transmission; seamless integration of data capture into the care process; the
value of having data available from a single point of access through which data
mining, forecasting, and modeling can be performed; and the basic necessity of a
criterion standard metric for quantifying surge capacity. Further consensus work
is needed to select a criterion standard metric for quantifying surge capacity.
These consensus statements cover the future research needs, the infrastructure
needs, and the data that are needed for a state-of-the-art approach to surge and
surge capacity.
PMID- 17032946
TI - The measurement of daily surge and its relevance to disaster preparedness.
AB - This article reviews what is known about daily emergency department (ED) surge
and ED surge capacity and illustrates its potential relevance during a
catastrophic event. Daily ED surge is a sudden increase in the demand for ED
services. There is no well-accepted, objective measure of daily ED surge. The
authors propose that daily and catastrophic ED surge can be measured by the
magnitude of the surge, as well as by the nature and severity of the illnesses
and injuries that patients present with during the surge. The magnitude of an ED
surge can be measured by the patient arrival rate per hour. The nature and
severity of the surge can be measured by the type (e.g., trauma vs. infection vs.
biohazard) and acuity (e.g., triage level) of the surge. Surge capacity is
defined as the extent to which a system can respond to a rapid and sizeable
increase in the demand for resources. ED surge capacity includes multiple
dimensions, such as systems, space, staffing, and supplies. A multidimensional
measure is needed that reflects both the core components and their relative
contribution to ED surge capacity. Although many types of factors may influence
ED surge capacity, relatively little formal research has been conducted in this
area. A better understanding of daily ED surge capacity and influencing factors
will improve our ability to simulate the potential impact that different types of
catastrophic events may have on the surge capacity of hospital EDs nationwide.
PMID- 17032947
TI - Research priorities for surge capacity.
AB - The 2006 Academic Emergency Medicine Consensus Conference discussed key concepts
within the field of surge capacity. Within the breakout session on research
priorities, experts in disaster medicine and other related fields used a
structured nominal-group process to delineate five critical areas of research. Of
the 14 potential areas of discovery identified by the group, the top five were
the following: 1) defining criteria and methods for decision making regarding
allocation of scarce resources, 2) determining effective triage protocols, 3)
determining key decision makers for surge-capacity planning and means to evaluate
response efficacy (e.g., incident command), 4) developing effective communication
and information-sharing strategies (situational awareness) for public-health
decision support, and 5) developing methods and evaluations for meeting workforce
needs. Five working groups were formed to consider the above areas and to devise
sample research questions that were refined further by the entire group of
participants.
PMID- 17032948
TI - Caveat usare: actuarial schemes in real life.
PMID- 17032949
TI - Suicide risk assessment: is clinical experience enough?
PMID- 17032950
TI - Diversion to the mental health system: emergency psychiatric evaluations.
AB - In Maryland, any citizen may petition to have individuals brought against their
will for an examination by a physician. In this retrospective chart review, we
evaluated the characteristics of 300 persons referred to the Johns Hopkins
Hospital on emergency petitions. Sixty-one percent of petitions described
individuals who made verbal or physical threats of self-harm. Forty-seven percent
of the petitions described individuals who could have been arrested based on
dangerousness to others or property, but were instead diverted to the emergency
room for psychiatric evaluation. Although not promoted as a jail diversion
program, this process has the potential to direct mentally ill citizens
appropriately from the criminal justice system into the mental health system.
Greater involvement of mental health professionals at all stages, including
police training and participation in crisis response teams in the community, may
improve this process.
PMID- 17032951
TI - Use of the criminal justice system to leverage mental health treatment: effects
on treatment adherence and satisfaction.
AB - In efforts to divert persons with mental illness from jails and prisons, the
option of community mental health treatment in lieu of incarceration is sometimes
offered. In addition, community treatment can be mandated, or "leveraged," as a
condition of probation or parole. However, little is known about the
characteristics and attitudes of persons who are and who are not leveraged into
community mental health treatment via the criminal justice (CJ) system. In the
present study, over 1,000 outpatients with mental disorders were queried about
their experiences with CJ leverages, as well as their clinical and treatment
histories. Persons who had experienced at least one form of CJ leverage were more
likely to be younger and male and to have more hospitalizations than persons who
had never experienced a CJ leverage. However, leverage experience was not
associated with treatment compliance and satisfaction, or perceptions of coercion
and mandate efficacy, particularly when demographic characteristics were
considered.
PMID- 17032952
TI - Commentary: coerced community mental health treatment--an added burden on an
overstretched system.
AB - The sudden and massive depopulation of psychiatric institutions that occurred in
the 60s and 70s overwhelmed a fragmented and undersourced community mental health
system, leading, in part, to the high number of chronically mentally ill
individuals currently residing in jails and prisons, a situation that has been
described as reinstitutionalization or transinstitutionalization. Any process
that forces more people out of jails into mental health treatment in the
community without a sound, effective, available, and accessible community mental
health system of care is potentially catastrophic.
PMID- 17032953
TI - Cultural stereotypes die hard: the case of transracial adoption.
AB - Transracial adoption (commonly understood as the adoption of black children by
white families) has been the subject of a persistent debate among adoption
specialists, legal advocates, mental health professionals, and even civil rights
advocates in this country for a long time. This has been so despite cumulative
research evidence indicating that transracial adoptees can thrive and develop
into confident adults with strong senses of identity and self-esteem. We contend
that the evidence undergirding transracial adoption has not been effectively
persuasive because of the tenacious and ubiquitous cultural belief that children
and their potential adoptive parents should be matched along racial lines.
However, the cultural principle of racial matching has also been diluted by
judicial decisions that have narrowly allowed the use of race as one factor
rather than as the controlling factor in adoption decisions. This article focuses
on the use of a third element--federal statutory attempts intended to remove race
as a controlling factor in child placement decisions. We will show how as a
matter of public policy, the statutory efforts were meant to promote race-neutral
approaches to adoption and to support transracial adoptions. However, in
practice, the statutory attempts may still leave the door open to continued race
matching, which suggests that the cultural preference for race-matching in the
construction of families remains powerfully ingrained and difficult to eradicate.
As a consequence, transracial adoption appears to maintain its status as a
culturally suspect phenomenon.
PMID- 17032954
TI - Commentary: cultural stereotypes can and do die: it's time to move on with
transracial adoption.
AB - This commentary argues that the Multiethnic Placement Act, designed to combat
common cultural stereotypes, provides clear guidance to state child welfare
agencies and the mental health professionals that serve them, eliminating any
regular consideration of race in the foster and adoptive placement of children.
Given recent enforcement action by the U.S. Department of Health and Human
Services, those who ignore this guidance act at peril of subjecting state
agencies to the significant financial penalties mandated for any violation of the
law.
PMID- 17032955
TI - Commentary: transracial adoption--changing trends and attitudes.
AB - Legislating adoption practices is a stop-gap measure to protect the interests of
potential adoptees and their would-be parents. As our society becomes better able
to govern itself in these matters and reaches a consensus on humanitarian values,
it is hoped that the need for legislation will diminish. In the meantime, we
still have the best-interests test to guide us through new and sometimes troubled
waters. We need to instill respect for all minority cultures while also
incorporating them into the larger culture that one day will appreciate the
values of tolerance and diversity.
PMID- 17032956
TI - A study of geriatric forensic evaluees: who are the violent elderly?
AB - The objective of this study was to examine a sample (n = 99) of elderly forensic
evaluees to describe the psychiatric, medical, legal, and demographic
characteristics of the sample and to examine which of these factors is associated
with violent charges. Clinical data were gathered through retrospective chart
review of patients aged 60 and over who were referred for criminal
responsibility/competency-to-stand-trial evaluations from 1991 to 1998 at William
S. Hall Psychiatric Institute in Columbia, South Carolina. Most (67.7%) of the
sample was alcohol dependent, nearly one half (44.4%) had dementia, and close to
one third (32.3%) had antisocial personality disorder. The majority of patients
(60.6%) were facing violent charges and most (80.8%) were recidivists. In
multivariate analysis, race, outpatient treatment status, crime location, and
paranoia were all associated with violent charges. The implications and
limitations of these data as applied to forensic treatment settings are
discussed.
PMID- 17032958
TI - Warning a potential victim of a person's dangerousness: clinician's duty or
victim's right?
AB - The legal duty of a psychiatrist or psychotherapist to warn an identifiable
victim of a patient's serious threat of harm has been well recognized in U.S.
jurisprudence and clinical practice since the Tarasoff decision of the Supreme
Court of California in 1976. Warning practices vary over a spectrum ranging from
those that are essentially legally required duties of clinicians to those based
on rights of actual or potential victims to be warned of a specific event. These
practices can be categorized as follows: (1) warning of the risk of violence; (2)
warning of the threat of violence; (3) requested warning; and (4) criminal
victims' warning mandated by statute. As legal requirements and clinical
standards for Tarasoff-type warnings continue to evolve, it behooves mental
health professionals to recognize these four different types of warnings.
Although not all are equally supported in law, all four practices can appear to
carry some measure of legal obligation.
PMID- 17032957
TI - Commentary: older offenders--no place to go?
AB - For offender groups, difficulties in definition of 'elderly' and 'older' are
considerable. Adoption of chronological age cutoffs gives little indication of
service need. Contrary to popular belief, there has been no upsurge of offending
among people of 60 and over, but there has been an increase in their
representation in the prison population. Older prisoners tend to have more mental
and physical health care needs than younger prisoners and than their similarly
aged peers in the community. Their needs may be more appropriately met in health
care rather than criminal justice services. Neither health care nor criminal
justice services, however, have yet made adequate specific provision for this
group. Our commentary reviews current evidence for more appropriate and safer
service responses.
PMID- 17032959
TI - Long-term follow-up of exhibitionists: psychological, phallometric, and offense
characteristics.
AB - Exhibitionism has historically been viewed as more of a nuisance than a serious
criminal justice matter. Research has demonstrated that the number of
exhibitionists who are detected re-offending is a significant under
representation of the number who actually re-offend. The objective of this study
was to extend a previous study conducted on exhibitionists, while attempting to
solve the limitations described in that study. Two hundred eight exhibitionists
were assessed at a university teaching hospital between 1983 and 1996. Archival
data were derived from police and medical files. Results indicated that, over a
mean follow-up period of 13.24 years, 23.6, 31.3, and 38.9 percent of
exhibitionists were charged with or convicted of sexual, violent, or criminal
offenses, respectively. Undoubtedly, this is an under-representation of the true
rate, as we have no way of knowing how many exhibitionists re-offended and did
not get caught. Nevertheless, in the present investigation, sexual recidivists
compared with non-recidivists were less educated, scored higher on the Michigan
Alcohol Screening Test (MAST), the Psychopathy Checklist, Revised (PCL-R), and
the Pedophile Index. Violent recidivists were also less educated and scored
higher on the MAST, PCL-R, and the Pedophile Index, and had accumulated a greater
number of prior violent or criminal charges and/or convictions. Criminal
recidivists were less educated; scored higher on the MAST, Buss-Durkee Hostility
Inventory (BDHI), PCL-R, and Pedophile Index; and had accumulated a greater
number of prior sexual, violent, and criminal offenses. Finally, the hands-on
sexual recidivists accumulated a greater number of prior violent and criminal
charges and or convictions than did the hands-off sexual recidivists.
PMID- 17032960
TI - The performance of incarcerated juveniles on the MacArthur Competence Assessment
Tool-Criminal Adjudication (MacCAT-CA).
AB - The MacArthur Competency Assessment Tool-Criminal Adjudication (MacCAT-CA) is a
structured interview that assesses abilities related to an individual's
competency to stand trial (CST). In the present study, we examined the
performance of 247 juvenile offenders on the scales of the MacCAT-CA
(Understanding, Reasoning, and Appreciation), along with several other variables
(age, IQ, achievement level, experience with the juvenile justice system, and a
screen for psychopathology) that may be related to CST. In general, results
suggest that performance on the MacCAT-CA varied with age, with younger
participants performing significantly worse than older juveniles. When compared
with the normative data, the juveniles in the present sample demonstrated
deficits in court-related skills measured by the MacCAT-CA across all age ranges.
In addition, several other variables, including achievement level, intelligence
level, and psychopathology, were differentially related to the three scales of
the MacCAT-CA.
PMID- 17032961
TI - Asperger's disorder and criminal behavior: forensic-psychiatric considerations.
AB - Asperger's Disorder remains an under-diagnosed condition because of clinical
unfamiliarity with its adult presentation. As forensic clinicians become familiar
with the presentation of Asperger's disorder, it appears that affected
individuals are over-represented in forensic criminal settings. Unique features
of such persons may heighten their risks for engaging in criminal behavior. Both
Theory of Mind deficits and a predilection for intense narrow interests, when
coupled with deficient social awareness of salient interpersonal and social
constraints on behavior, can result in criminal acts. We discuss comorbidities of
forensic relevance. We present several cases that highlight these issues and
review the relevant forensic literature. Furthermore, there may be valid
questions as to degree of criminal responsibility in such persons. From a
neuropsychiatric perspective, these disorders appear to have a biological
underpinning for deficits in empathy, a finding that may have important
repercussions when assessing remorse in criminal proceedings.
PMID- 17032963
TI - Commentary: psychiatric advance directives at a crossroads--when can PADs be
overridden?
AB - Current statutes enabling psychiatric advance directives (PADs) typically include
provisions allowing override of patients' choices by treatment staff. Lest the
purpose of the PAD be vitiated by too broad an application of the override
mechanism, its use should be carefully limited. In inpatient settings, voluntary
patients should have the right to decline treatments in advance, although not an
absolute right to demand treatments of their choosing. The situation of
involuntary patients is more complex. Permitting PADs to trump commitment
statutes would undercut the combined parens patriae/police power rationale for
commitment, a path taken currently by no U.S. jurisdiction. Moreover, PADs should
not be permitted to negate the usual mechanisms for involuntary treatment of
committed patients; to do otherwise risks forcing facilities to confine
indefinitely persons they cannot treat. Even in those circumstances, however,
where PADs provide evidence of reasonable patient preferences (e.g., for one
medication over another), the choices they embody should be respected.
PMID- 17032962
TI - Superseding psychiatric advance directives: ethical and legal considerations.
AB - Psychiatric advance directives (PADs) were introduced in the 1980s as legal
instruments for psychiatric patients to retain some choice over their own mental
health treatment during periods of decisional incapacity. However, PADs are
nested in larger structures of mental health law and policy that protect the
interests of parties other than the patient, and which, in situations of conflict
involving the treatment of incapacitated patients, tend to favor the clinician's
professional judgment over the patient's manifest wishes to avoid standard
treatment. Thus, PADs are trumped by civil commitment law and may also be legally
overridden by clinicians who, acting in good faith, consider PAD instructions to
be inconsistent with accepted clinical standards of care. We discuss
philosophical-ethical and legal issues surrounding overriding PADs and offer
analysis of the possible future of legal cases in which the question of
overriding PADs and fiscal concerns may collide.
PMID- 17032964
TI - Commentary: toward resolving some dilemmas concerning psychiatric advance
directives.
AB - Dilemmas about when psychiatric advance directives (PADs) should be overridden
are complicated by conflicting legal frameworks that may nonetheless operate
concurrently-a legal scheme based on decision-making capacity (or competency) set
against a legal scheme based on civil commitment, in which the latter may "trump"
the former. A single statute in which the strengths of both schemes are "fused"
may be possible. There is evidence that the promise of PADs in enhancing
patients' control over their treatment can be achieved without legislation for
PADs and where civil commitment is given legal precedence. An example is the
"joint crisis plan" in which, through a negotiation facilitated by an independent
third party, a joint agreement is reached between patient and service provider
about what treatment should be given when, as a result of a relapse of mental
illness, the patient loses the ability to make treatment decisions. This clinical
instrument may significantly reduce later involuntary treatment.
PMID- 17032965
TI - Commentary: the climate for physician adherence to psychiatric advance
directives.
AB - Factors that may be significant in rationalizing physician overrides of
psychiatric advance directives (PADs) are not only features of individual
clinical scenarios, but also are artifacts of the faltering mental health system
being navigated by both provider and patient. This system, frequently viewed as
hostile to consumer choice and increasingly focused on reacting to recurrent
crises, is not predisposed to accepting proactive, person-centered measures such
as PADs. In fact, PADs may hold great promise in improving clinical outcomes and
even reducing system costs. But to realize the full potentials of PADs requires
that providers understand their roles in challenging or perpetuating problems in
the larger mental health system.
PMID- 17032966
TI - Electroconvulsive therapy: administrative codes, legislation, and professional
recommendations.
AB - Government regulatory involvement in electroconvulsive therapy (ECT) is due to
several factors, including patient advocate groups, prior abuse by psychiatrists,
and a general trend of state authority to move into areas traditionally governed
by medical authorities. Regardless of the specific reasons, ECT is both highly
effective in the treatment of many psychiatric disorders and heavily regulated by
state administrative codes and legislation. The purpose of this article is to
conduct a systematic review of the state administrative codes and legislation for
the 50 states, the District of Columbia, and Puerto Rico and to compare the
findings with professional recommendations for the administration of ECT.
PMID- 17032974
TI - The cover. An October Day.
PMID- 17032975
TI - A piece of my mind. The imaginary safety net.
PMID- 17032976
TI - Genetic link found for premature birth risk.
PMID- 17032977
TI - High suicide risk found for patients with head and neck cancer.
PMID- 17032978
TI - Insulin effects weigh heavy on the brain.
PMID- 17032979
TI - Aging brings new challenges for polio survivors.
PMID- 17032980
TI - Pharmacotherapy and behavioral intervention for alcohol dependence.
PMID- 17032981
TI - Pharmacotherapy and behavioral intervention for alcohol dependence.
PMID- 17032982
TI - Inside baseball.
PMID- 17032983
TI - Inside baseball.
PMID- 17032984
TI - Glucose fluctuations and oxidative stress.
PMID- 17032985
TI - Translation of research evidence from animals to humans.
PMID- 17032986
TI - Risk of myocardial infarction in patients with psoriasis.
AB - CONTEXT: Psoriasis is the most common T-helper cell type 1 (T(H)1) immunological
disease. Evidence has linked T(H)1 diseases to myocardial infarction (MI).
Psoriasis has been associated with cardiovascular diseases, but has only been
investigated in hospital-based studies that did not control for major
cardiovascular risk factors. OBJECTIVE: To determine if within a population-based
cohort psoriasis is an independent risk factor for MI when controlling for major
cardiovascular risk factors. DESIGN, SETTING, AND PATIENTS: A prospective,
population-based cohort study in the United Kingdom of patients with psoriasis
aged 20 to 90 years, comparing outcomes among patients with and without a
diagnosis of psoriasis. Data were collected by general practitioners as part of
the patient's medical record and stored in the General Practice Research Database
between 1987 and 2002, with a mean follow-up of 5.4 years. Adjustments were made
for hypertension, diabetes, history of myocardial infarction, hyperlipidemia,
age, sex, smoking, and body mass index. Patients with psoriasis were classified
as severe if they ever received a systemic therapy. Up to 5 controls without
psoriasis were randomly selected from the same practices and start dates as the
patients with psoriasis. A total of 556,995 control patients and patients with
mild (n = 127,139) and severe psoriasis (n = 3837) were identified. MAIN OUTCOME
MEASURE: Incident MI. RESULTS: There were 11,194 MIs (2.0%) within the control
population and 2319 (1.8%) and 112 (2.9%) MIs within the mild and severe
psoriasis groups, respectively. The incidences per 1000 person-years for control
patients and patients with mild and severe psoriasis were 3.58 (95% confidence
interval [CI], 3.52-3.65), 4.04 (95% CI, 3.88-4.21), and 5.13 (95% CI, 4.22
6.17), respectively. Patients with psoriasis had an increased adjusted relative
risk (RR) for MI that varied by age. For example, for a 30-year-old patient with
mild or severe psoriasis, the adjusted RR of having an MI is 1.29 (95% CI, 1.14
1.46) and 3.10 (95% CI, 1.98-4.86), respectively. For a 60-year-old patient with
mild or severe psoriasis, the adjusted RR of having an MI is 1.08 (95% CI, 1.03
1.13) and 1.36 (95% CI, 1.13-1.64), respectively. CONCLUSIONS: Psoriasis may
confer an independent risk of MI. The RR was greatest in young patients with
severe psoriasis.
PMID- 17032987
TI - Respiratory symptoms, pulmonary function, and markers of inflammation among bar
workers before and after a legislative ban on smoking in public places.
AB - CONTEXT: Scotland prohibited smoking in confined public places on March 26, 2006.
OBJECTIVE: To investigate the association of smoke-free legislation with
symptoms, pulmonary function, and markers of inflammation of bar workers. DESIGN,
SETTING, AND PARTICIPANTS: This prospective observational study was conducted in
Tayside, Scotland from February-June 2006. One hundred five nonasthmatic and
asthmatic nonsmoking bar workers were initially enrolled, of whom 77 completed
the study per protocol. MAIN OUTCOME MEASURES: Respiratory and sensory symptoms,
spirometry measurements, serum cotinine levels, peripheral inflammatory cell
count, asthma quality-of-life scores, and exhaled nitric oxide levels were
evaluated before and after introduction of the smoking ban. RESULTS: For the per
protocol analysis, the percentage of bar workers with respiratory and sensory
symptoms decreased from 79.2% (n = 61) before the smoke-free policy to 53.2% (n =
41) (total change, -26%; 95% confidence interval [CI], -13.8% to -38.1%; P<.001)
and 46.8% (n = 38) (-32.5%; 95% CI, -19.8% to -45.2%; P<.001) 1 and 2 months
afterward. Forced expiratory volume in the first second increased from 96.6%
predicted to 104.8% (change, 8.2%; 95% CI, 3.9% to 12.4%; P<.001) and then 101.7%
(change, 5.1%; 95% CI, 2.1% to 8.0%; P = .002), and serum cotinine levels
decreased from 5.15 ng/mL to 3.22 ng/mL (change, -1.93 ng/mL; 95% CI, -2.83 to
1.03 ng/mL; P<.001) and then 2.93 ng/mL (-2.22 ng/mL; 95% CI, -3.10 to -1.34
ng/mL; P<.001). The total white blood cell and neutrophil count was reduced from
7610 to 6980 cells/microL at 2 months (-630 cells/muL; 95% CI, -1010 to -260
cells/microL; P = .002) and from 4440 to 4030 cells/microL (-410 cells/microL;
95% CI, -740 to -90 cells/microL; P = .03), respectively. Asthmatic bar workers
also had less airway inflammation, with a reduction in exhaled nitric oxide from
34.3 parts per billion (ppb) to 27.4 ppb 1 month after the ban (0.8-fold change;
95% CI, 0.67 to 0.96 ppb; P = .04), and Juniper quality-of-life scores increased
from 80.2 to 87.5 points (7.3 points; 95% CI, 0.1 to 14.6 points; P = .049).
CONCLUSIONS: Smoke-free legislation was associated with significant early
improvements in symptoms, spirometry measurements, and systemic inflammation of
bar workers. Asthmatic bar workers also had reduced airway inflammation and
improved quality of life.
PMID- 17032988
TI - Long-term outcome of primary percutaneous coronary intervention vs prehospital
and in-hospital thrombolysis for patients with ST-elevation myocardial
infarction.
AB - CONTEXT: Whether the superior results of percutaneous coronary intervention (PCI)
reported in clinical trials in which patients with ST-segment elevation
myocardial infarction (STEMI) received reperfusion treatment can be replicated in
daily practice has been questioned, especially whether it is superior to
prehospital thrombolysis (PHT). OBJECTIVE: To evaluate the outcome of different
reperfusion strategies in consecutive STEMI patients. DESIGN, SETTING, AND
PATIENTS: A prospective observational cohort study of 26 205 consecutive STEMI
patients in the Register of Information and Knowledge about Swedish Heart
Intensive Care Admissions (RIKS-HIA) who received reperfusion therapy within 15
hours of symptom onset. The registry includes more than 95% of all Swedish
patients, of all ages, who were treated in a coronary intensive care unit between
1999 and 2004. INTERVENTIONS: Seven thousand eighty-four patients underwent
primary PCI; 3078, PHT; and 16 043, in-hospital thrombolysis (IHT). MAIN OUTCOME
MEASURES: Mortality, reinfarction, and readmissions as reported in the National
Health Registries through December 31, 2005. RESULTS: After adjusting for younger
age and less comorbidity, primary PCI was associated with lower mortality than
IHT at 30 days (344 [4.9%] vs 1834 [11.4%]; hazard ratio [HR], 0.61; 95%
confidence interval [CI], 0.53-0.71) and at 1 year (541 [7.6%] vs 2555 [15.9%];
HR, 0.68; 95% CI, 0.60-0.76). Also primary PCI correlated with lower mortality
than PHT at 30 days (344 [4.9%] vs 234 [7.6%]; HR, 0.70; 95% CI, 0.58-0.85) and 1
year (541 [7.6%] vs 317 [10.3%]; HR, 0.81; 95% CI, 0.69-0.94). Prehospital
thrombolysis predicted a lower mortality than IHT at 30 days (HR, 0.87; 95% CI,
0.76-1.01) and at 1 year (HR, 0.84; CI 0.74-0.95). Beyond 2 hours' treatment
delay, the observed mortality reductions with PHT tended to decrease while the
benefits with primary PCI seemed to remain regardless of time delay. Primary PCI
was also associated with shorter hospital stay and less reinfarction than either
PHT or IHT. CONCLUSIONS: In unselected patients with STEMI, primary PCI, which
compared favorably with IHT and PHT, was associated with reduced duration of
hospital stay, readmission, reinfarction, and mortality.
PMID- 17032989
TI - Nonmedical exemptions to school immunization requirements: secular trends and
association of state policies with pertussis incidence.
AB - CONTEXT: School immunization requirements have played a major role in controlling
vaccine-preventable diseases in the United States. Most states offer nonmedical
exemptions to school requirements (religious or personal belief). Exemptors are
at increased risk of acquiring and transmitting disease. The role of exemption
policies may be especially important for pertussis, which is endemic in the
United States. OBJECTIVE: To determine if (1) the rates of nonmedical exemptions
differ and have been increasing in states that offer only religious vs personal
belief exemptions; (2) the rates of nonmedical exemptions differ and have been
increasing in states that have easy vs medium and easy vs difficult processes for
obtaining exemptions; and (3) pertussis incidence is associated with policies of
granting personal belief exemptions, ease of obtaining exemptions, and acceptance
of parental signature as sufficient proof of compliance with school immunization
requirements. DESIGN, SETTING, AND PARTICIPANTS: We analyzed 1991 through 2004
state-level rates of nonmedical exemptions at school entry and 1986 through 2004
pertussis incidence data for individuals aged 18 years or younger. MAIN OUTCOME
MEASURES: State-level exemption rates and pertussis incidence. RESULTS: From 2001
through 2004, states that permitted personal belief exemptions had higher
nonmedical exemption rates than states that offered only religious exemptions,
and states that easily granted exemptions had higher nonmedical exemption rates
in 2002 through 2003 compared with states with medium and difficult exemption
processes. The mean exemption rate increased an average of 6% per year, from
0.99% in 1991 to 2.54% in 2004, among states that offered personal belief
exemptions. In states that easily granted exemptions, the rate increased 5% per
year, from 1.26% in 1991 to 2.51% in 2004. No statistically significant change
was seen in states that offered only religious exemptions or that had medium and
difficult exemption processes. In multivariate analyses adjusting for
demographics, easier granting of exemptions (incidence rate ratio = 1.53; 95%
confidence interval, 1.10-2.14) and availability of personal belief exemptions
(incidence rate ratio = 1.48; 95% confidence interval, 1.03-2.13) were associated
with increased pertussis incidence. CONCLUSIONS: Permitting personal belief
exemptions and easily granting exemptions are associated with higher and
increasing nonmedical US exemption rates. State policies granting personal belief
exemptions and states that easily grant exemptions are associated with increased
pertussis incidence. States should examine their exemption policies to ensure
control of pertussis and other vaccine-preventable diseases.
PMID- 17032990
TI - Do opiates affect the clinical evaluation of patients with acute abdominal pain?
AB - CONTEXT: Clinicians have traditionally withheld opiate analgesia from patients
with acute abdominal pain until after evaluation by a surgeon, out of concern
that analgesia may alter the physical findings and interfere with diagnosis.
OBJECTIVE: To determine the impact of opiate analgesics on the rational clinical
examination and operative decision for patients with acute abdominal pain. DATA
SOURCES AND STUDY SELECTION: MEDLINE (through May 2006), EMBASE, and hand
searches of article bibliographies to identify placebo-controlled randomized
trials of opiate analgesia reporting changes in the history, physical examination
findings, or diagnostic errors (those resulting in "management errors," defined
as the performance of unnecessary surgery or failure to perform necessary surgery
in a timely fashion). DATA EXTRACTION: Two authors independently reviewed each
study, abstracted data, and classified study quality. A third reviewer
independently resolved discrepancies. DATA SYNTHESIS: Studies both in adults (9
trials) and in children (3 trials) showed trends toward increased risks of
altered findings on the abdominal examination due to opiate administration, with
risk ratios for changes in the examination of 1.51 (95% confidence interval [CI],
0.85 to 2.69) and 2.11 (95% CI, 0.60 to 7.35), respectively. When the analysis
was restricted to the 8 adult and pediatric trials that reported significantly
greater analgesia for patients who received opiates compared with those who
received placebo, the risk of physical examination changes became significant
(risk ratio, 2.13; 95% CI, 1.14 to 3.98). These trials exhibited significant
heterogeneity (I2 = 68.6%; P = .002), and only 2 trials distinguished clinically
significant changes such as loss of peritoneal signs from all other changes;
consequently, we analyzed risk of management errors as a marker for important
changes in the physical examination. Opiate administration had no significant
association with management errors (+0.3% absolute increase; 95% CI, -4.1% to
+4.7%). The 3 pediatric trials showed a nonsignificant absolute decrease in
management errors (-0.8%; 95% CI, -8.6% to +6.9%). Across adult and pediatric
trials with adequate analgesia, opiate administration was associated with a
nonsignificant absolute decrease in the risk of management errors (-0.2%; 95% CI,
-4.0% to +3.6%). CONCLUSIONS: Opiate administration may alter the physical
examination findings, but these changes result in no significant increase in
management errors. The existing literature does not rule out a small increase in
errors, but this error rate reflects a conservative definition in which surgeries
labeled as either delayed or unnecessary may have met appropriate standards of
care. In published research reports, no patient experienced major morbidity or
mortality attributable to opiate administration.
PMID- 17032991
TI - Plan B and the politics of doubt.
PMID- 17032992
TI - Banning smoking in public places: time to clear the air.
PMID- 17032994
TI - JAMA patient page. Acute abdominal pain.
PMID- 17032995
TI - Letter to the editor: The suckling-micturition reflex in cows.
PMID- 17032996
TI - Modeling high-intensity pulsed electric field inactivation of a lipase from
Pseudomonas fluorescens.
AB - The inactivation kinetics of a lipase from Pseudomonas fluorescens (EC 3.1.1.3.)
were studied in a simulated skim milk ultrafiltrate treated with high-intensity
pulsed electric fields. Samples were subjected to electric field intensities
ranging from 16.4 to 27.4 kV/cm for up to 314.5 micros, thus achieving a maximum
inactivation of 62.1%. The suitability of describing experimental data using
mechanistic first-order kinetics and an empirical model based on the Weibull
distribution function is discussed. In addition, different mathematical
expressions relating the residual activity values to field strength and treatment
time are supplied. A first-order fractional conversion model predicted residual
activity with good accuracy (A(f) = 1.018). A mechanistic insight of the model
kinetics was that experimental values were the consequence of different
structural organizations of the enzyme, with uneven resistance to the pulsed
electric field treatments. The Weibull model was also useful in predicting the
energy density necessary to achieve lipase inactivation.
PMID- 17032997
TI - Ionic calcium determination in skim milk with molecular probes and front-face
fluorescence spectroscopy: simple linear regression.
AB - The purpose of this study was to determine if the ionic calcium content of skim
milk could be determined using molecular probes and front-face fluorescence
spectroscopy. Current methods for determining ionic calcium are not sensitive,
overestimate ionic calcium, or require complex procedures. Molecular probes
designed specifically for measuring ionic calcium could potentially be used to
determine the ionic calcium content of skim milk. The goal of the current study
was to develop foundation methods for future studies to determine ionic calcium
directly in skim milk and other dairy products with molecular probes and
fluorescence spectroscopy. In this study, the effect of pH on calcium-sensitive
fluorescent probe (Rhod-5N and Fluo-5N) performance using various concentrations
of skim milk was determined. The pH of diluted skim milk (1.9 to 8.9% skim milk),
was adjusted to either 6.2 or 7.0, after which the samples were analyzed with
fluorescent probes (1 microM) and front-face fluorescence spectroscopy. The ionic
calcium content of each sample was also determined using a calcium ion-selective
electrode. The results demonstrated that the ionic calcium content of each sample
was highly correlated (R2 > 0.989) with the fluorescence intensities of the probe
calcium adduct using simple linear regression. Higher than suggested ionic
calcium contents of 1,207 and 1,973 microM were determined with the probes (Fluo
5N and Rhod-5N) in diluted skim milk with pH 7.0 and 6.2, respectively. The
fluorescence intensity of the probe-calcium adduct decreased with a decrease in
pH for the same ionic calcium concentration. This study demonstrates that Fluo-5N
and Rhod-5N can be used to determine the ionic-calcium content of diluted milk
with front-face fluorescence spectroscopy. Furthermore, these probes may also
have the potential to determine the ionic calcium content of undiluted skim milk.
PMID- 17032998
TI - Improving the yield of Mozzarella cheese by phospholipase treatment of milk.
AB - Part-skim Mozzarella cheese was manufactured from milk hydrolyzed with fungal
phospholipase A1 prior to renneting. The phospholipase treatment reduced fat
losses in whey and cooking water and increased cheese yield as a result of
improved fat and moisture retention in the cheese curd. The amount of
phospholipids in the whey was reduced because of improved retention of
lysophospholipids in the cheese curd. Water binding in the fresh curds and young
cheeses up to 3 wk of storage was investigated by a 1H nuclear magnetic resonance
spin-spin relaxation technique. In the fresh curds, 2 dominant water fractions
were present, characterized by average spin-spin relaxation times (T2) of 14 and
86 to 89 ms, respectively. These 2 fractions of low- and high-molecular-mobility
water were similar in all cheeses and presumed to represent water associated with
the casein matrix and water present in the pores. A few hours after manufacture,
cheeses made with phospholipase showed decreased T2 of the high-mobility
fraction, indicating improved water-holding capacity. It is suggested that
lysophospholipids released from the fat globule membranes act as surface-active
agents in the cheese curd, helping emulsification of water and fat during
processing and reducing syneresis. During 3 wk of storage after manufacture, the
mobility of both water fractions increased in all cheeses, but was highest in the
cheeses made with phospholipase. The increase in mobility during the first weeks
of storage has earlier been ascribed to structural changes in the protein matrix,
which in principle could be accelerated because of the higher moisture content.
However, the microstructure of phospholipase-treated cheese was investigated by
confocal laser scanning microscopy and found to be very similar to the control
cheese during processing and up to 28 d of storage. In addition, flowability,
stretchability, and browning were acceptable and similar in all the manufactured
cheeses. Thus, phospholipase hydrolysis of cheese milk improved the cheese yield
without changing the cheese microstructure, and resulted in cheese with
functional properties that were identical to traditional Mozzarella cheese.
PMID- 17032999
TI - Comparison of the compositional, microbiological, biochemical, and volatile
profile characteristics of nine Italian ewes' milk cheeses.
AB - Nine Italian ewes' milk cheeses were compared for compositional, microbiological,
biochemical, and volatile profile characteristics. Mean values for the gross
composition were rather similar among cheeses. The lowest pH values were found
for cheeses that used primary starters. At the end of ripening, cheeses made from
raw milk contained >6.0 log10 cfu/g of nonstarter lactic acid bacteria. Several
species of lactobacilli were identified, but Lactobacillus plantarum and
Lactobacillus paracasei were dominant. Random amplified polymorphic DNA-PCR
analysis showed the biodiversity among the strains, and in several cases a
relationship with the cheese of provenance. Cheeses differed mainly for secondary
proteolysis, as shown by the principal component analysis applied to reversed
phase fast protein liquid chromatography data of the pH 4.6-soluble fractions and
by determination of the free AA. A total of 113 volatile components were
identified in the Italian Pecorino cheeses by solid-phase microextraction coupled
with gas chromatography-mass spectrometry analysis. The volatile profiles of the
9 cheeses differed significantly. Quantitatively, alcohols were the most abundant
chemical class for some cheeses, whereas ketones were the most abundant for other
cheeses. Esters and carboxylic acids were largely found. Specific volatile
components seemed to distinguish specific cheeses.
PMID- 17033000
TI - Cheese pH, protein concentration, and formation of calcium lactate crystals.
AB - The occurrence of calcium lactate crystals (CLC) in hard cheeses is a continual
expense to the cheese industry, as consumers fail to purchase cheeses with this
quality defect. This research investigates the effects of the protein
concentration of cheese milk and the pH of cheese on the occurrence of CLC.
Atomic absorption spectroscopy was used to determine total and soluble calcium
concentrations in skim milk (SM1, 8.7% total solids), and skim milk supplemented
with nonfat dry milk (CSM1, 13.5% total solids). Calcium, phosphorus, lactic
acid, and citrate were determined in cheeses made with skim milk (SM2, 3.14%
protein), skim milk supplemented with ultrafiltered milk (CSM2, 6.80% protein),
and nonfat dry milk (CSM3, 6.80% protein). Supplementation with nonfat dry milk
increased the initial total calcium in CSM1 (210 mg/100 g of milk) by 52%
compared with the total calcium in SM1 (138 mg/100 g of milk). At pH 5.4, soluble
calcium concentrations in CSM1 were 68% greater than soluble calcium in SM1. In
cheeses made from CSM2 and CSM3, total calcium was 26% greater than in cheeses
made from SM2. As the pH of cheeses made from SM2 decreased from 5.4 to 5.1, the
concentration of soluble calcium increased by 61.6%. In cheeses made from CSM2
and CSM3, the concentrations of soluble calcium increased by 41.4 and 45.5%,
respectively. Calcium lactate crystals were observed in cheeses made from SM2 at
and below pH 5.1, whereas CLC were observed in cheeses from CSM2 and CSM3 at and
below pH 5.3. The increased presence of soluble calcium can potentially cause CLC
to occur in cheese manufactured with increased concentrations of milk solids,
particularly at and below pH 5.1.
PMID- 17033001
TI - Detection and quantification of capsular exopolysaccharides from Streptococcus
thermophilus using lectin probes.
AB - The aim of this work was to use fluorescently labeled lectins to develop a
convenient and reliable method to determine the relative abundance of capsular
polysaccharides (CPS) at the surface of Streptococcus thermophilus MR-1C cells.
Fluorescein isothiocyanate-labeled peanut agglutinin isolated from Arachis
hypogaea was found to interact specifically with the CPS of Strep. thermophilus
MR-1C. This labeled lectin was then used as an effective probe to detect and
quantify CPS. A fluorescence-based lectin-binding assay was successfully applied
to follow the accumulation of CPS during the growth of Strep. thermophilus MR-1C
in milk and in M17 broth supplemented with lactose. Our results showed that in
both media, CPS production by Strep. thermophilus MR-1C began during the
exponential phase of growth and continued for several hours after the culture
reached the stationary growth phase.
PMID- 17033002
TI - Evaluation of environmental sampling and culture to determine Mycobacterium avium
subspecies paratuberculosis distribution and herd infection status on US dairy
operations.
AB - The objectives of this study were to determine the distribution of Mycobacterium
avium subspecies paratuberculosis (MAP) in the environment and assess the
relationship between the culture status of MAP in the farm environment and herd
infection status. The National Animal Health Monitoring System's Dairy 2002 study
surveyed dairy operations in 21 states. One component of the study involved
collection and culturing of environmental samples for MAP from areas on farms
where manure accumulated from a majority of a herd's cows. Operations were
selected for inclusion based on perceived risk factors for MAP infection
identified in a previously administered questionnaire. Individual animal and
environmental samples were collected and used to determine the efficiency of
environmental sampling for determination of herd infection status. Individual
animal fecal, serum, and milk samples were used to classify herds as infected or
not infected based on the presence of at least one test-positive animal in the
herd. A total of 483 environmental samples (approximately 5 per farm) were
collected, and 218 (45.1%) were culture-positive for MAP. A similar percentage of
environmental cultures collected from all designated areas were positive [parlor
exits (52.3%), floors of holding pens (49.1%), common alleyways (48.8%), lagoons
(47.4%), manure spreaders (42.3%), and manure pits (41.5%)]. Of the 98 operations
tested with the environmental sample culture, 97 had individual serum ELISA
results, 60 had individual fecal culture results, and 34 had individual milk
ELISA results. Sixty-nine of the 98 operations (70.4%) had at least one
environmental sample that was culture-positive. Of the 50 herds classified as
infected by fecal culture, 38 (76.0%) were identified by environmental culture.
Two of the 10 operations classified as not infected based on individual animal
fecal culture were environmental culture-positive. Of the 80 operations
classified as infected based on serum ELISA-positive results, 61 (76.3%) were
identified as environmental-positive, whereas 20 of the 28 (71.4%) operations
identified as infected based on milk ELISA were detected by environmental
sampling. Environmental sample culturing is less costly than individual animal
sampling, does not require animal restraint, and identified more than 70% of
infected operations. Environmental sampling is another diagnostic tool that
veterinarians and dairy producers can use to determine herd infection status for
MAP.
PMID- 17033003
TI - Short communication: Regulation of milk fat yield and fatty acid composition by
insulin.
AB - Diet-induced milk fat depression in dairy cows has been known for many years and
several theories have been proposed. One that continues to receive support is the
glucogenic-insulin theory. Previous studies testing this theory using a
hyperinsulinemic-euglycemic clamp have had variable results attributable to
variability in the use of body fat reserves as a source of milk fatty acids. Our
objective was to test the glucogenic-insulin theory using cows immediately
postpartum, a period when the use of body fat for milk fat synthesis is greatest.
During wk 2 postpartum, 5 cows were given a 2-d baseline period and then clamped
for 4 d. Insulin was increased more than 2-fold during the clamp while the blood
glucose concentration was maintained. Milk yield was not altered by
administration of the clamp (38.7 vs. 39.0 +/- 1.4 kg/d); however, the milk fat
percentage and yield were reduced by 27% and plasma nonesterified fatty acids
were reduced by 68%. Analysis of the milk fatty acid composition revealed that
the decrease in milk fat yield during use of the clamp was almost exclusively due
to reductions in preformed fatty acids; this is the exact opposite of what is
observed with diet-induced milk fat depression. Therefore, our results do not
support the glucogenic-insulin theory of diet-induced milk fat depression. The
results further indicated that reductions in milk fat observed previously with
hyperinsulinemic-euglycemic clamps or with glucose or propionate infusions were
most likely consequences of the ability of insulin to inhibit lipolysis, thereby
limiting the mammary availability of preformed fatty acids mobilized from body
reserves.
PMID- 17033004
TI - Milking frequency, estradiol cypionate, and somatotropin influence lactation and
reproduction in dairy cows.
AB - Our objectives were to determine lactational and reproductive outcomes in
response to increased milking frequency (MF), injection of estradiol cypionate
(ECP), and treatment with bovine somatotropin (bST). Lactating dairy cows (n =
144) were blocked by lactation number (1 vs. 2+) and assigned randomly to a 2 x 2
x 2 factorial experiment consisting of 8 treatment combinations: 1) MF consisting
of 4x daily milking (4x) for the first 30 d in milk (DIM) vs. 2x daily milking
(2x), with all cows milked 2x after 30 DIM; 2) 10 mg of ECP given postpartum at 8
+/- 3 DIM versus controls that received ECP diluent (oil); and 3) biweekly bovine
somatotropin (bST), starting sometime after 60 DIM, versus no bST. Ovulation
before the first artificial insemination was synchronized by using Heatsynch
(GnRH injection 7 d before PGF2alpha followed in 24 h by ECP), and cows were
artificially inseminated after detected estrus or at 48 h after ECP, whichever
came first. Pregnancy was assessed by transrectal ultrasonography 28 to 30 d
after artificial insemination. Daily yield and weekly components of milk were
measured during the first 90 DIM. Intervals to first and second postpartum
ovulation were unaffected by treatment, but cows were in estrus earlier after 2x
(24 +/- 4 d) than 4x (41 +/- 4 d) daily MF, and sooner after ECP (25 +/- 3 d)
than after oil (39 +/- 4 d) treatment. Pregnancy rates among 4x cows increased
for ECP versus oil (52.8 vs. 27.8%) more than for cows with 2x MF treated with
ECP versus oil (50.0 vs. 39.4%). Increased MF increased daily milk yields and
energy-corrected milk yields during the first 30 DIM. Although milk yields were
increased acutely by ECP during the 10 d after its injection, subsequent milk
yields were decreased for ECP-treated cows previously milked 4x daily. Treatment
with bST increased overall daily milk yields most in cows previously milked 2x
daily and treated with oil and those milked 4x daily and treated with ECP. We
concluded that early postpartum ECP injection increased pregnancy rates, but
generally had detrimental effects on milk yields after 30 DIM for ECP-treated
cows previously milked 4x daily, unless those cows also were treated with bST.
PMID- 17033005
TI - Effect of cis-urocanic acid on bovine neutrophil generation of reactive oxygen
species.
AB - Neutrophils play a fundamental role in the host innate immune response during
mastitis and other bacterial-mediated diseases of cattle. One of the critical
mechanisms by which neutrophils contribute to host innate immune defenses is
through their ability to phagocytose and kill bacteria. The ability of
neutrophils to kill bacteria is mediated through the generation of reactive
oxygen species (ROS). However, the extracellular release of ROS can be
deleterious to the host because ROS induce tissue injury. Thus, in diseases such
as mastitis that are accompanied by the influx of neutrophils, the generation of
large quantities of ROS may result in significant injury to the mammary
epithelium. cis-Urocanic acid (cis-UCA), which is formed from the UV
photoisomerization of the trans isoform found naturally in human and animal skin,
is an immunosuppressive molecule with anti-inflammatory properties. Little is
known about the effect of cis-UCA on neutrophils, although one report
demonstrated that it inhibits human neutrophil respiratory burst activity.
However, the nature of this inhibition remains unknown. Because of the potential
therapeutic use that a molecule such as cis-UCA may have in blocking excessive
respiratory burst activity that may be deleterious to the host, the ability of
cis-UCA to inhibit bovine neutrophil production of ROS was studied. Further,
because neutrophil generation of ROS is necessary for optimal neutrophil
bactericidal activity, a response which is critical for the host innate immune
defense against infection, the effects of cis-UCA on bovine neutrophil
phagocytosis and bacterial killing were assayed. cis-Urocanic acid dose
dependently inhibited the respiratory burst activity of bovine neutrophils as
measured by luminol chemiluminescence. Subsequently, the effect of cis-UCA on the
production of specific oxygen radicals was investigated using more selective
assays. Using 2 distinct assays, we established that cis-UCA inhibited the
generation of extracellular superoxide. In contrast, cis-UCA had no effect on the
generation of intracellular levels of superoxide or other ROS. At concentrations
that inhibited generation of extracellular superoxide, bovine neutrophil
phagocytosis and bacterial activity remained intact. Together, these data suggest
that cis-UCA inhibits the tissue-damaging generation of extracellular ROS while
preserving neutrophil bactericidal activity.
PMID- 17033006
TI - Short communication: In vitro antimicrobial susceptibility of Prototheca
wickerhamii and Prototheca zopfii isolated from bovine mastitis.
AB - Bovine mastitis caused by Prototheca spp. can assume high significance because of
economic losses and the potential risk to public health. Studies on the
susceptibility of Prototheca spp. to antimicrobials have demonstrated its high
level of resistance. We report the susceptibility of bovine isolates of
Prototheca wickerhamii and Prototheca zopfii to amphotericin B and nystatin, 2
antifungal agents commonly used in the control of protothecosis, and discuss the
results. After subculture, minimum inhibitory concentrations of both antifungal
drugs were determined using macrodilution and agar diffusion methods. The
inoculum concentration was standardized by determination of colony-forming units
per milliliter. Nystatin showed more efficacy than amphotericin B in inhibiting
P. wickerhamii growth. In contrast, growth inhibition of P. zopfii was similar
for both antifungal agents. This study demonstrates different in vitro
susceptibility patterns of P. wickerhamii and P. zopfii, reinforcing the
necessity for more investigation into drugs that can be used with clinical
efficacy.
PMID- 17033008
TI - Omitting the dry-off period negatively affects colostrum and milk yield in dairy
goats.
AB - Seventeen pregnant multiparous Murciano-Granadina dairy goats, kept in a semi
intensive exploitation system with once daily milking throughout lactation and 1
kidding per year (milk yield, 577 L/300 d), were used to study the effects of dry
off period length on performance during the subsequent lactation. Goats were
mated at wk 29 of lactation and were assigned to 2 experimental groups according
to dry-off treatment: goats that were dried off 56 d before expected kidding
(D56; n = 9) and goats without dry-off (D0; n = 8). After parturition, kids were
removed from their mothers and weighed before suckling. Goats were hand milked to
obtain colostrum and were machine milked thereafter. Colostrum was sampled for
composition and IgG analysis. Milk yield was recorded weekly during the preceding
and subsequent lactations. Udders were biopsied in a sample of goats at d -65
(late lactation), d -49 (during dry-off), and d 48 (early lactation) to kidding
(d 0). Apoptotic and proliferating cells in mammary tissues were detected
immunohistochemically. Five goats (63%) in the D0 group dried off spontaneously
at 27 +/- 4 d before kidding and were considered separately (D27). The rest of
the D0 goats yielded 0.86 L/d from d -56 to kidding. Goats kidded 2.25 kids/goat,
but the D0 kids had smaller birth weights (1.7 kg) than the D27 (2.2 kg) and D56
(2.1 kg) kids. Colostrum of the D0 goats contained less IgG (5.6 mg/mL) than the
D27 (32.9 mg/mL) and the D56 (42.4 mg/mL) goats. In the subsequent lactation (210
d), the D0 goats produced less milk (1.78 L/d) than the D27 (2.51 L/d) and D56
(2.24 L/d) goats, with no detectable difference between the D27 and D56 goats.
Apoptosis and proliferation indices increased from 0.51 and 2.09%, at d -65, to
1.75 and 7.12% at d -49 (d 7 of dry-off) in D56 goats. Despite differences in
daily milk yield during early lactation (d 48) between the D0, D27, and D56
treatments (1.73, 2.68, and 2.53 L/d, respectively), no differences in apoptosis
or proliferation indices were detected (D0: 0.65 and 2.48%; D27: 0.68 and 1.37%;
and D56: 0.71 and 2.95%), indicating that duration of the dry period did not
affect mammary cell turnover during the subsequent lactation. Omitting the dry
period between lactations reduced the quality of colostrum and had negative
effects on milk yield in dairy goats. Goats dried off spontaneously for 27 d were
as productive as goats dried off for 56 d, indicating that less than 2 mo of dry
off may be sufficient in practice.
PMID- 17033007
TI - Reproduction in dairy cows following progesterone insert presynchronization and
resynchronization protocols.
AB - The objectives of this study were to evaluate the effects of an intravaginal
insert containing progesterone (CIDR, controlled internal drug releasing)
administered in presynchronization and resynchronization protocols on cyclicity,
detection of estrus, pregnancy rate, and pregnancy loss to first AI;
reinsemination patterns; and pregnancy rates to second postpartum AI before and
after the time of first-service pregnancy diagnosis in dairy cows. Holstein cows
(n = 1,052) were blocked by parity and BCS at 3 +/- 3 d in milk (study d 0 = day
of calving) and assigned randomly to 1 of 3 presynchronization treatments. During
the presynchronization programs, all cows received 2 injections of PGF2alpha, on
study d 35 and 49. Cows enrolled in the control presynchronization treatment
received AI after detected estrus from study d 49 to 62. Cows enrolled in the
CIDR estrus-detection (CED) presynchronization treatment received a CIDR insert
from study d 42 to 49 and AI on detection of estrus from d 49 to 62. Cows
enrolled in the CIDR timed AI (CTAI) presynchronization treatment received the
same treatment as CED, but were subjected to timed AI on study d 72 after the
Ovsynch (GnRH, 7 d PGF2alpha, 2 d GnRH, 24 h timed AI) protocol. The control and
CED cows not inseminated by study d 62 were enrolled in the Ovsynch protocol on
the same day and received timed AI on study d 72. After first AI, cows were
assigned to no resynchronization (RCON) or resynchronization with a CIDR insert
(RCIDR) between 14 and 21 d after AI. Blood samples collected on study d 35, 49,
and 62 were analyzed for concentrations of progesterone and cows were classified
as anestrous when progesterone was < 1.0 ng/mL in the first 2 samples. On study d
62, anestrous cows with progesterone > or = 1.0 ng/mL were classified as having
resumed cyclicity. Pregnancy was diagnosed at 31 and 60 d after first AI and at
42 d after second AI. A greater proportion of anestrous cows in CED and CTAI
became cyclic by d 62 postpartum than control cows. Resynchronization with the
CIDR insert increased the pregnancy rate at 31 d after first AI in CED and CTAI,
and at 60 d after AI in all cows because of reduced pregnancy loss. These results
indicate that presynchronization with the CIDR insert increased induction of
cyclicity in anestrous cows and that resynchronization with the CIDR insert did
not affect the reinsemination rate but did reduce pregnancy loss and increased
the pregnancy rate at 60 d after first AI.
PMID- 17033009
TI - Risk factors associated with Cryptosporidium infection on dairy farms in a New
York State watershed.
AB - A cross-sectional study was carried out to determine the prevalence of
Cryptosporidium parvum-like oocyst shedding on dairy farms in a watershed in New
York State and to identify the factors that put animals at risk. A proportional
sample of dairy herds in the targeted area was obtained, and animals were
selected using a stratified sampling design to ensure representation of the
population at risk. Fecal samples were collected per rectum and analyzed for the
presence of C. parvum-like oocysts using the quantitative centrifugation
concentration flotation technique and a proprietary enzyme-linked immunoassay.
Additionally, isolates of Cryptosporidium were examined via bidirectional DNA
sequencing. Data on putative risk factors were collected at the time of sampling
and analyzed for association using logistic regression. The herd prevalence was
42% and the overall animal prevalence was 3.2%. The prevalence among animals less
than 60 d of age was 20%. The likelihood of shedding Cryptosporidium decreased
with the age of the animal and varied with the type of barn water source. Both
the number of unweaned calves present at the time of the study, and whether the
calves were tied vs. not tied increased the risk of infection. There was
significant agreement between the flotation and PCR techniques. Sequencing
revealed that 50% of the isolates were Cryptosporidium bovis, an isolate thought
to be nonzoonotic.
PMID- 17033010
TI - Treatment with gonadotropin-releasing hormone after first timed artificial
insemination improves fertility in noncycling lactating dairy cows.
AB - Lactating Holstein cows were assigned randomly to treatments to improve fertility
after first postpartum timed artificial insemination (TAI). In Experiment 1, cows
received no treatment (control; n = 9), a controlled internal drug releasing
(CIDR) insert from 5 to 12 d after TAI (CIDR; n = 9), or 100 microg of GnRH 5 d
after TAI (G5; n = 7). Although treatments did not affect circulating
progesterone (P4) concentrations from 5 to 19 d after TAI, there was a tendency
for CIDR cows to have greater P4 compared with control or G5 cows within 24 h
after treatment. In 2 field trials, cows received either control (n = 223), CIDR
(n = 218), or G5 (n = 227) treatments (Experiment 2), or control (n = 160), G5 (n
= 159), or treatment with 100 microg of GnRH 7 d after TAI (G7; n = 163;
Experiment 3). Treatment did not affect pregnancies per AI (P/AI) in Experiments
2 or 3; however, when data were combined to compare control (n = 383) and G5 (n =
386) treatments, P/AI tended to be greater for G5 (49.1%) than for control
(45.8%) cows. This effect resulted from a GnRH treatment x cyclicity status
interaction in which P/AI for noncycling cows receiving G5 was greater than for
noncycling control cows (45.5 vs. 31.1%). In conclusion, treatment with CIDR
inserts after TAI had no effect on P/AI, whereas treatment with GnRH 5 d after
TAI improved P/AI for noncycling, but not for cycling cows.
PMID- 17033011
TI - Importance of the sampled milk fraction for the prediction of total quarter
somatic cell count.
AB - This study investigated the changes in somatic cell counts (SCC) in different
fractions of milk, with special emphasis on the foremilk and cisternal milk
fractions. Therefore, in Experiment 1, quarter milk samples were defined as
strict foremilk (F), cisternal milk (C), first 400 g of alveolar milk (A1), and
the remaining alveolar milk (A2). Experiment 2 included 6 foremilk fractions (F1
to F6), consisting of one hand-stripped milk jet each, and the remaining
cisternal milk plus the entire alveolar milk (RM). In Experiment 1, changes
during milking indicated the importance of the sampled milk fraction for
measuring SCC because the decrease in the first 3 fractions (F, C, and A1) was
enormous in milk with high total quarter SCC. The decline in SCC from F to C was
50% and was 80% from C to A1. Total quarter SCC presented a value of
approximately 20% of SCC in F or 35% of SCC in C. Changes in milk with low or
very low SCC were marginal during milking. Fractions F and C showed significant
differences in SCC among different total SCC concentrations. These differences
disappeared with the alveolar fractions A1 and A2. In Experiment 2, a more
detailed investigation of foremilk fractions supported the findings of Experiment
1. A significant decline in the foremilk fractions even of F1 to F6 was observed
in high-SCC milk at concentrations >350 x 10(3) cells/mL. Although one of these
foremilk fractions presented only 0.1 to 0.2% of the total milk, the SCC was 2-
to 3-fold greater than the total quarter milk SCC. Because the trait of interest
(SCC) was measured directly by using the DeLaval cell counter (DCC), the quality
of measurement was tested. Statistically interesting factors (repeatability,
recovery rate, and potential matrix effects of milk) proved that the DCC is a
useful tool for identifying the SCC of milk samples, and thus of grading udder
health status. Generally, the DCC provides reliable results, but one must
consider that SCC even in strict foremilk can differ dramatically from SCC in the
total cisternal fraction, and thus also from SCC in the alveolar fraction.
PMID- 17033012
TI - Effect of rubber flooring on claw health in lactating dairy cows housed in free
stall barns.
AB - Multiparous dairy cows between 10 to 30 d in milk (DIM) were enrolled in a
clinical trial to evaluate the effects of rubber flooring on the development of
claw lesions, locomotion scores, clinical lameness, and rates of hoof growth and
wear. Two groups of cows were housed in identical free-stall facilities, except
that 1 pen (rubber, n = 84) had rubber alley mats covering the entire concrete
floor of the pen, whereas cows in the second pen were exposed to concrete
flooring (concrete, n = 82) without rubber alley mats. All cows were evaluated 3
times between 10 and 30, 74 and 94, and 110 and 130 DIM for 1) the presence of
claw lesions on their rear feet, 2) the occurrence of clinical lameness based on
a locomotion score, and 3) rates of claw growth and wear as observed on the
dorsal wall of the right lateral claw. No differences between flooring groups at
the time of enrollment were detected for lactation number, mean DIM at first
examination, body condition score, and proportion of cows with claw lesions at
the first examination. Odds of developing claw lesions between examinations were
not different for cows exposed to the rubber surface compared with those exposed
to concrete. Cows on concrete, however, had greater odds of developing or
exacerbating existing heel erosion than cows on rubber flooring. Regardless of
the flooring surface, the lateral claw was more likely to develop lesions than
the medial claw. Odds of becoming lame by the third examination and the
proportion of cows requiring therapeutic hoof trimming because of lameness were
greater for concrete-exposed cows than those on rubber. Cows on rubber flooring
had decreased claw growth and wear between the first and last examination
compared with cows on concrete. Regardless of flooring surface, second-lactation
cows had greater wear rates than those in third or greater parities. Results of
our study suggest that a soft flooring surface, such as interlocking rubber, is
beneficial for hoof health.
PMID- 17033013
TI - Housing system, milk production, and zero-grazing effects on lameness and leg
injury in dairy cows.
AB - The aim of this study was to assess the effect of grazing (G) vs. zero-grazing
(ZG), level of milk production, and quality and type of housing system [free
stalls (FS) and straw yards (SY)] on the prevalence of lameness and leg injuries
in dairy cows. Observations were made on 37 commercial dairy farms across Great
Britain. A single visit of 5 d duration was made to each farm. During this visit,
lameness scores and the incidence of swellings, rubs, and injuries to hocks and
knees were recorded on all the peak- or mid-lactation cows. Aspects of the
quality of housing and management that were likely to affect foot and leg health
were recorded. There were more lame cows on ZG farms (39 +/- 0.02%) than on
grazing (G) farms (15 +/- 0.01%), and lameness scores were higher on FS farms
compared with SY farms (0.25 +/- 0.01 vs. 0.05 +/- 0.01). Cows on SY farms had
fewer hock and knee injuries compared with FS farms. The frequency of knee
swellings was higher on ZG farms (0.31 +/- 0.02) than on G farms (0.15 +/- 0.01).
Aspects of the free-stall design affected foot and leg health. The number of hock
swellings increased with increasing stall gradient (0.16 +/- 0.01 with no slope
vs. 0.39 +/- 0.02 at a 0 to 1.5% slope). There was an interaction between the
length of the free-stall lunging space and the hip width of the cow, indicating
that the incidence of lameness is generally highest on farms with small free
stalls and heavy cows. High levels of milk production did not affect lameness or
leg injury. The results indicate that housing cows throughout the year
potentially has a detrimental effect on foot and leg health. However, good free
stall design may reduce lameness and leg lesions.
PMID- 17033014
TI - Comparison of models to identify lame cows based on gait and lesion scores, and
limb movement variables.
AB - Bovine lameness results in pain and suffering in cattle and economic loss for
producers. A system for automatically detecting lame cows was developed recently
that measures vertical force components attributable to individual limbs. These
measurements can be used to calculate a number of limb movement variables. The
objective of this investigation was to explore whether gait scores, lesion
scores, or combined gait and lesion scores were more effectively captured by a
set of 5 limb movement variables. A set of 700 hind limb examinations was used to
create gait-based, lesion-based, and combined (gait- and lesion-based) models.
Logistic regression models were constructed using 1, 2, or 3 d of measurements.
Resulting models were tested on cows not used in modeling. The accuracy of lesion
score models was superior to that of gait-score models; lesion-based models
generated greater values of areas under the receiving operating characteristic
curves (range 0.75 to 0.84) and lower mean-squared errors (0.13 to 0.16) compared
with corresponding values for the gait-based models (0.63 to 0.73 and 0.26 to
0.31 for receiving operating characteristic and mean-squared errors,
respectively). These results indicate that further model development and
investigation could generate automated and objective methods of lameness
detection in dairy cattle.
PMID- 17033015
TI - Effects of body weight and nutrition on mammary protein expression profiles in
Holstein heifers.
AB - A proteomics approach was used to characterize biochemical and cellular
mechanisms governing effects of peripubertal feeding on heifer mammary
development. Mammary parenchymal tissue from 24 Holstein heifers randomly
assigned to treatments arranged in a 2 x 2 factorial design was used to generate
2-dimensional protein maps of mammary tissue extracts. Heifers were reared on 1
of 2 dietary treatments, restricted (650 g/ d of daily gain) or elevated (950 g/d
of daily gain) and killed at 1 of 2 body weights (BW, 200 or 350 kg). Cytosolic
mammary gland extracts were prepared from frozen mammary parenchyma. Proteome
maps of extracts were constructed using PDQuest software. Densities of 820
protein spots were analyzed using the MIXED procedure of SAS. Protein spots were
characterized by changes in profiles of expression in response to increased BW,
dietary treatment, or both. Dietary treatment influenced the expression of 131
protein spots, whereas heifer BW influenced the expression of 108 spots. The 22
most highly influenced (statistically) spots were excised and submitted for mass
spectrometric analyses. Returned protein names and accession numbers were used in
National Center for Biotechnology Information database searches to obtain
information on the identified proteins. For example, one of the proteins that
differed by dietary treatment, transferrin, a binding protein of insulin-like
growth factor binding protein-3, was identified via these methods. Possible roles
of this and other proteins in mammary development are described. We concluded
that a proteomic approach is an effective tool for identifying the proteins
involved in bovine mammary development.
PMID- 17033016
TI - Developmental and nutritional regulation of the prepubertal heifer mammary gland:
I. Parenchyma and fat pad mass and composition.
AB - Prior to puberty, elevated nutrient intake has been shown to negatively affect
prepubertal mammary development in the heifer. The objective of this study was to
evaluate the effects of increased nutrient intake on mammary development in
Holstein heifers at multiple body weights from birth through puberty.
Specifically, this study evaluated the effects of nutrient intake and body weight
at harvest on 1) total weight and DNA content of the parenchyma (PAR) and mammary
fat pad (MFP) and 2) PAR and MFP composition. Starting at 45 kg of body weight,
heifers (n = 78) were assigned to either a restricted (R) or elevated (E) level
of nutrient intake supporting 650 (R) or 950 (E) g/d of body weight gain. Heifers
were harvested at 50-kg increments from 100 to 350 kg of body weight. Mammary fat
pad weight and DNA content were greater in E- than in R-heifers. Additionally, E
heifers had a greater fraction of lipids and a smaller fraction of protein in
their MFP than did R-heifers. Parenchyma weight and DNA were lower in E- than in
R-heifers; however, when analyzed with age as a covariate term, treatment was no
longer a significant term in the model. Level of nutrient intake had no effect on
the lipid, protein, or hydroxyproline composition of the PAR. Collectively, these
data demonstrate that PAR is refractory to the level of nutrient intake whereas
MFP is not. Furthermore, the covariate analysis demonstrated that age at harvest,
not the level of nutrient intake, was the single greatest determinant of total
PAR DNA content.
PMID- 17033017
TI - Developmental and nutritional regulation of the prepubertal bovine mammary gland:
II. Epithelial cell proliferation, parenchymal accretion rate, and allometric
growth.
AB - It is well documented that elevated nutrient intake prior to puberty reduces
prepubertal mammary development in the bovine. The companion paper demonstrated
that age at harvest is a primary determinant of parenchymal (PAR) mass and that
any effects of elevated energy intake on mechanisms regulating mammary
development are dwarfed by this effect of time. Therefore, it is hypothesized
that while causing a decrease in prepubertal PAR mass, elevated nutrient intake
will have no effect on growth characteristics of the mammary gland. The
objectives of this experiment were to evaluate the effects of increased nutrient
intake from early in life on 1) mammary epithelial cell proliferation, 2) mammary
PAR DNA accretion rates, and 3) the dynamics of prepubertal allometric PAR
growth. Holstein heifers (n = 78) were fed from 45 kg of body weight either
elevated (E) or restricted (R) levels of nutrients to support 950 (E) or 650 (R)
g/d of body weight gain. Six heifers per treatment were harvested at 50-kg
increments from 100 to 350 kg of body weight. Heifers on the E plane of nutrition
had higher plasma leptin and less PAR DNA than their body weight-matched R-intake
cohorts. Despite this reduction in PAR DNA, treatment did not negatively
influence mammary epithelial cell proliferation or the PAR DNA accretion rate.
Dynamics of allometric and isometric mammary growth were also unaffected by the
level of nutrient intake, as was exit from allometric growth. This work
represents the first demonstrating that the level of nutrient intake and the
concomitant increase in plasma leptin have no measurable influence on 1) the rate
of PAR DNA accretion, 2) mammary epithelial cell proliferation, or 3) total PAR
mass and, by default, the local or systemic controls that coordinate these
processes.
PMID- 17033018
TI - Feeding a low manganese diet to heifers during gestation impairs fetal growth and
development.
AB - A study was conducted to examine the effects of low dietary Mn on growth
performance of pregnant heifers and fetal development of their offspring. Twenty
pregnant Angus (n = 9) and Simmental (n = 11) heifers averaging 17 mo of age and
447.6 kg of initial body weight were used in the 267-d study. Heifers were
selected from a previous study examining the effects of supplemental Mn on growth
and reproductive performance of heifers. Ten pregnant heifers per treatment from
the control (analyzed at 15.8 mg of Mn/kg of DM) and supplemental Mn (50 mg/kg of
DM) treatments were randomly selected at the conclusion of the previous study to
continue on their respective dietary treatments through gestation and early
lactation. Serum cholesterol for the 267-d period was not affected by treatment.
Whole-blood Mn concentration of heifers on d 267 was not affected by treatment.
Whole-blood Mn concentration at birth was lower in calves born to control heifers
than in those born to supplemented heifers. Calves born to control heifers
weighed less at birth than those born to heifers receiving supplemental Mn.
Calves born to control heifers suffered from varying signs of Mn deficiency,
including superior brachygnathism, unsteadiness, disproportionate dwarfism, and
swollen joints. Results suggest that feeding gestating heifers a diet containing
16.6 mg of Mn/kg of DM is not adequate for proper fetal development.
Supplementation of 50 mg of Mn/kg of DM to the control diet was sufficient to
overcome any signs of Mn deficiency in calves.
PMID- 17033019
TI - Effect of feeding frequency of a total mixed ration on the performance of high
yielding dairy cows.
AB - Forty Finnish Ayrshire cows, 16 primiparous and 24 multiparous, were randomly
assigned to 1 of 2 treatments (FF1 or FF5). Total mixed ration (TMR) was fed once
a day on the FF1 treatment and 5 times a day on the FF5 treatment. The experiment
began at calving and continued to wk 28 of lactation. The TMR consisted of a
grass silage and concentrate mix. The amount of concentrate in the TMR was 51% on
a DM basis. The feeding frequency had no effect on milk or energy-corrected milk
yields or on milk composition. The average energy-corrected milk yield was 32.8
kg/d on the FF1 treatment and 32.5 kg/d on the FF5 treatment. The less frequent
feeding increased the dry matter intake (DMI) of cows. The average DMI during the
experiment was 20.9 kg/d on the FF1 treatment and 19.9 kg/d on the FF5 treatment.
The difference in DMI was due to the differences in DMI of the mature cows.
Energy and protein conversion tended to be lower with feeding once a day compared
with feeding 5 times a day. The cows' feeding behavior was also observed. Cows
fed 5 times a day tended to eat quite evenly after each delivery, whereas on the
FF1 treatment there were 2 clear feeding peaks in the evening after the feed
delivery. The time spent eating during the observation period was longer on FF5
than on FF1. The cows fed once a day spent more time lying than the cows fed 5
times a day. Based on the observations of feeding behavior, feeding a TMR 5 times
a day seemed to be too frequent based on the increased restlessness and decreased
lying time of the cows.
PMID- 17033020
TI - Effect of barley and its amylopectin content on ruminal fermentation and nitrogen
utilization in lactating dairy cows.
AB - The effect of type of grain (corn vs. barley) and amylopectin content of barley
grain (normal vs. waxy) on ruminal fermentation, digestibility, and utilization
of ruminal ammonia nitrogen for milk protein synthesis was studied in a
replicated 3 x 3 Latin square design trial with 6 lactating dairy cows. The
experimental treatments were (proportion of dietary dry matter): CORN, 40% corn
grain, NBAR, 30% normal Baronesse barley:10% corn grain, and WBAR, 30% high
amylopectin (waxy) Baronesse barley:10% corn grain. All grains were steam-rolled
and fed as part of a total mixed ration. The NBAR and WBAR diets resulted in
increased ruminal ammonia concentrations compared with CORN (8.2, 7.4, and 5.6
mM, respectively), but other ruminal fermentation parameters were not affected.
Ruminal digestibility of dietary nutrients and microbial protein synthesis in the
rumen were also not affected by diet. Corn grain had greater in situ effective
ruminal dry matter degradability (62.8%) than the barley grains (58.2 and 50.7%,
respectively), and degradability of the normal barley starch was greater than
that of the waxy barley (69.3 and 58.9%, respectively). A greater percentage of
relative starch crystallinity was observed for the waxy compared with the normal
barley grain. Total tract apparent digestibility of dry matter and organic matter
were decreased by WBAR compared with CORN and NBAR. Total tract starch
digestibility was greater and milk urea nitrogen content was lower for CORN
compared with the 2 barley diets. In this study, the extent of processing of the
grain component of the diet was most likely the factor that determined the diet
responses. Minimal processing of barley grain (processing indexes of 79.2 to
87.9%) reduced its total tract digestibility of starch compared with steam-rolled
corn (processing index of 58.8%). As a result of the increased ammonia
concentration and reduced degradability of barley dry matter in the rumen, the
utilization of ruminal ammonia nitrogen for microbial protein synthesis was
decreased with the barley diets compared with the corn-based diet. In this study,
waxy Baronesse barley was less degradable in the rumen and the total digestive
tract than its normal counterpart. The most likely reasons for these effects were
the differences in starch characteristics and chemical composition, and perhaps
the different response to processing between the 2 barleys.
PMID- 17033021
TI - Short communication: Eicosatrienoic acid and docosatrienoic acid do not promote
vaccenic acid accumulation in mixed ruminal cultures.
AB - Previous research found that docosahexaenoic acid (C22:6n-3) was a component of
fish oil that promotes trans-C18:1 accumulation in ruminal cultures when
incubated with linoleic acid. The objective of this study was to determine if
eicosatrienoic acid (C20:3n-3) and docosatrienoic acid (C22:3n-3), n-3 fatty
acids in fish oil, promote accumulation of trans-C18:1, vaccenic acid (VA) in
particular, using cultures of mixed ruminal microorganisms. Treatments consisted
of control, control plus 5 mg of C20:3n-3 (ETA), control plus 5 mg of C22:3n-3
(DTA), control plus 15 mg of linoleic acid (LA), control plus 5 mg of C20:3n-3
and 15 mg of linoleic acid (ETALA), and control plus 5 mg of C22:3n-3 and 15 mg
of linoleic acid (DTALA). Treatments were incubated in triplicate in 125-mL
flasks, and 5 mL of culture contents was taken at 0 and 24 h for fatty acid
analysis by gas-liquid chromatography. After 24 h of incubation, the
concentrations of trans-C18:1 (0.87, 0.88, and 0.99 mg/culture), and VA (0.52,
0.56, and 0.62 mg/culture) were similar for the control, ETA, and DTA cultures,
respectively. The concentrations of trans-C18:1 (5.51, 5.41, and 5.36
mg/culture), and VA (4.78, 4.62, and 4.59 mg/culture) were also similar between
LA, ETALA, and DTALA cultures, respectively. These data suggest that C20:3n-3 and
C22:3n-3 are not the active components in fish oil that promote VA accumulation
when incubated with linoleic acid.
PMID- 17033022
TI - Effect of casein and propionate supply on mammary protein metabolism in lactating
dairy cows.
AB - The effects of casein (CN) and propionate (C3) on mammary AA metabolism were
determined in 3 multiparous Holstein cows fitted with both duodenal and ruminal
cannulas and used in a replicated Youden square with six 14-d periods. Casein
(743 g/d in the duodenum) and C3 (1,041 g/d in the rumen) infusions were tested
in a factorial arrangement. For each period, L-[1-(13)C]Leu (d 11) and NaH[13C]O3
(d 13) were infused into a jugular vein, and blood samples were taken from the
carotid artery and the mammary vein to determine Leu kinetics and net uptake of
AA. Both CN and C3 treatments separately increased milk protein concentration and
yield. With CN there was a general response in mammary protein metabolism,
involving increases in Leu net uptake (30%), the uptake:output ratio (8%),
protein synthesis (11%), secretion in milk protein (21%), and oxidation (259%).
In contrast, C3 treatments tended to increase only Leu in milk protein (7%) and,
when in combination with CN, to reduce Leu used for protein synthesis (5%).
Across all treatments, most Leu uptake by the mammary gland was accounted for as
Leu in milk or oxidized, and the Leu balance was therefore achieved without
involvement of either net peptide use or production. Mammary uptake of group 1 AA
increased to match milk output with all infusions. In contrast, mammary uptake of
group 2 AA exceeded output to a greater extent with CN than with C3 infusions,
whereas the increment in uptake of group 3 AA increased with C3 treatments.
Overall, these data suggest that different mechanisms operate to improve milk
protein production when either protein or energy is supplied.
PMID- 17033023
TI - Effects of addition of essential oils and monensin premix on digestion, ruminal
fermentation, milk production, and milk composition in dairy cows.
AB - Four ruminally cannulated, lactating Holstein cows were used in a 4 x 4 Latin
square design (28-d periods) with a 2 x 2 factorial arrangement of treatments to
study the effects of dietary addition of essential oils (0 vs. 2 g/d; EO) and
monensin (0 vs. 350 mg/d; MO) on digestion, ruminal fermentation characteristics,
milk production, and milk composition. Intake of dry matter averaged 22.7 kg/d
and was not significantly affected by dietary additives. Apparent digestibilities
of dry matter, organic matter, neutral detergent fiber, and starch were similar
among treatments. Apparent digestibility of acid detergent fiber was increased
when diets were supplemented with EO (48.9 vs. 46.0%). Apparent digestibility of
crude protein was higher for cows fed MO compared with those fed no MO (65.0 vs.
63.6%). Nitrogen retention was not changed by additive treatments and averaged
27.1 g/d across treatments. Ruminal pH was increased with the addition of EO
(6.50 vs. 6.39). Ruminal ammonia nitrogen (NH3-N) concentration was lower with MO
supplemented diets compared with diets without MO (12.7 vs. 14.3 mg/100 mL). No
effect of EO and MO was observed on total volatile fatty acid concentrations and
molar proportions of individual volatile fatty acids. Protozoa counts were not
affected by EO and MO addition. Production of milk and 4% fat-corrected milk was
similar among treatments (33.6 and 33.4 kg/d, respectively). Milk fat content was
lower for cows fed MO than for cows fed diets without MO (3.8 vs. 4.1%). The
reduced milk fat concentration in cows fed MO was associated with a higher level
of trans-10 18:1, a potent inhibitor of milk fat synthesis. Milk urea nitrogen
concentration was increased by MO supplementation, but this effect was not
apparent when MO was fed in combination with EO (interaction EO x MO). Results
from this study suggest that feeding EO (2 g/d) and MO (350 mg/d) to lactating
dairy cows had limited effects on digestion, ruminal fermentation
characteristics, milk production, and milk composition.
PMID- 17033024
TI - Effects of supplementing concentrates differing in carbohydrate composition in
veal calf diets: I. Animal performance and rumen fermentation characteristics.
AB - The aim of this experiment was to examine the effects of concentrates in feed,
differing in carbohydrate source, on the growth performance and rumen
fermentation characteristics of veal calves. For this purpose, 160 Holstein
Friesian x Dutch Friesian crossbred male calves were used in a complete
randomized block design with a 5 x 2 factorial arrangement. Dietary treatments
consisted of 1) milk replacer control, 2) pectin-based concentrate, 3) neutral
detergent fiber-based concentrate, 4) starch-based concentrate, and 5) mixed
concentrate (equal amounts of concentrates of treatments 2, 3, and 4).
Concentrate diets were provided as pellets in addition to a commercial milk
replacer. Calves were euthanized either at the end of 8 or 12 wk of age. The
overall dry matter intake of the concentrate diets varied between 0.37 and 0.52
kg/d. Among the concentrate diets, the dry matter intake was lower in the starch
diet (0.37 kg/d of dry matter) and differed between the NDF and pectin diets. The
average daily gain for all the dietary treatments varied between 0.70 and 0.78
kg/d. The mixed- and NDF-fed calves had an increased average daily gain (0.78 and
0.77 kg/d, respectively) compared with the starch- and pectin-fed calves (0.70
and 0.71 kg/d, respectively). Rumen fermentation in the calves fed concentrates
was characterized by a low pH (4.9 to 5.2), volatile fatty acid concentrations
between 100 and 121 mmol/L, and high concentrations of reducing sugars (33 to 66
g/kg of dry matter). The volatile fatty acid concentrations of calves fed
concentrates were higher than those of the control calves. All concentrate
treatments showed a low acetate-to-propionate ratio in rumen fluid (between 1.3
and 1.9). Among the concentrates, the NDF diet had the highest (55.5%) and starch
the lowest (45.5%) molar proportions of acetate. Calves fed the mixed, pectin,
and starch diets had significantly higher molar proportions of butyrate (13.1 to
15.8%) than the NDF- and control-fed groups (9.9 and 9.6%, respectively). Calves
fed the control diet had a higher lactate concentration (21 mmol/L) than the
concentrate-fed calves (between 5 and 11 mmol/L). With the exception of the NDF
diet, polysaccharide-degrading enzyme activities in the rumen contents generally
showed an adaptation of the microorganisms to the carbohydrate source in the
diet. The mixed diet exhibited the least variation in rumen polysaccharide
degrading enzyme activities among the enzymes systems tested. Results indicated
that the carbohydrate source can influence intake, growth rate, and rumen
fermentation in young veal calves.
PMID- 17033025
TI - Effects of supplementing concentrates differing in carbohydrate composition in
veal calf diets: II. Rumen development.
AB - The objective of this experiment was to examine the effects of concentrates in
feed, differing in carbohydrate source, on the rumen development of veal calves.
For this purpose, 160 male Holstein Friesian x Dutch Friesian crossbred calves
were used in a complete randomized block design with a 5 x 2 factorial
arrangement. Dietary treatments consisted of 1) a milk replacer control, 2) a
pectin-based concentrate, 3) a neutral detergent fiber-based concentrate, 4) a
starch-based concentrate, and 5) a mixed concentrate (equal amounts of the
concentrates in treatments 2, 3, and 4). Concentrate diets were provided as
pellets in addition to a commercial milk replacer. Calves were euthanized at
either 8 or 12 wk of age. Plasma acetate and beta-hydroxybutyrate (BHBA) were
measured as indicators of rumen development. Empty rumen weight was determined,
and wall samples were taken at slaughter. In most calves, a poorly developed
rumen mucosa was observed. Coalescing rumen papillae with embedded hair, feed
particles, and cell debris were found in all calves fed the concentrate diets.
Calves fed concentrates had significantly heavier rumens than calves fed the
control diet. In the dorsal location of the rumen, calves fed concentrate diets
showed an increased ratio of mucosa to serosa length compared with calves fed the
control diet, whereas in the ventral location only, calves fed the pectin and
mixed diets showed larger ratios of mucosa to serosa length. Mucosa thickness and
muscle thickness were greater in the ventral and dorsal locations of the rumen,
respectively. In both locations, the NDF diet resulted numerically in the lowest
mucosa thickness and highest muscle thickness among the concentrate treatments.
At 8 wk, calves fed the concentrate diets had higher plasma acetate
concentrations than calves on the control treatment. However, at 12 wk, only NDF
fed calves showed significantly higher plasma acetate concentrations. The plasma
BHBA concentrations of calves at 8 wk of age fed the pectin and mixed diets were
higher than those of the control diet-fed calves. At 12 wk, no differences in
BHBA concentrations were observed among treatments. Results of a principal
component analysis indicated that, in addition to rumen volatile fatty acid
concentrations, other factors were likely to affect rumen development, and that
the relationships between rumen development and individual types of volatile
fatty acids present in the rumen liquor were similar. Also, variations in rumen
development coincided with variations in plasma acetate and BHBA concentrations.
PMID- 17033026
TI - Effect of different forms of methionine on lactational performance of dairy cows.
AB - Methionine is one of the first limiting AA in dairy cows. The use of rumen
protected Met to correct deficient diets is limited by the lack of a product that
could be incorporated into a pelleted concentrate. The main objective of this
trial was to test, at practical doses (approximately 10 g of absorbable Met), the
efficacy of 2 forms of pelletable Met hydroxy analogs, D,L-2-hydroxy-4
(methylthio)-butanoic acid (HMB) and the isopropyl ester of HMB (HMBi), to
provide Met to cows, especially for milk protein synthesis, compared with a
negative control and to Smartamine M (SmM). These treatments were tested
according to a 4 x 4 Latin square in 16 Holstein cows. Plasma Met concentrations
were increased by 110 and 65% that of the control value after HMBi and SmM
treatments, respectively. Milk protein yield increased by 32 and 41 g/d for HMBi
and SmM, respectively. D,L-2-hydroxy-4-(methylthio)-butanoic acid supplementation
did not improve Met availability to the cows for milk protein synthesis. The HMBi
treatment induced an increase in 15:0 in milk at the expense of a general
reduction in even-numbered short-and medium-chain fatty acids. Moreover, HMBi and
SmM supplements led to an increase in the saturation level of C18 fatty acids
consistent with the improvement of Met supply. It was concluded that HMBi is a
new "rumen-protected" form of Met that can be supplied to cows integrated into
pellets.
PMID- 17033027
TI - Slow-release urea and highly fermentable sugars in diets fed to lactating dairy
cows.
AB - This experiment was designed to test the inclusion of highly fermentable sugars
(FS) in dairy rations and their interactions with a slow-release urea (SU)
product. The FS are a blend of liquid coproducts from the corn milling and cheese
industries, and the SU is calcium chloride urea. Eight multiparous and 4
primiparous Brown Swiss cows (117 +/- 46 d in milk) were blocked by parity and
utilized in a multiple Latin square design. Basal diets were formulated for 16.6%
crude protein and 1.55 Mcal/kg of net energy for lactation and contained 35% of
dietary dry matter as corn silage, 15% alfalfa hay, 34% of a concentrate mix
containing varying proportions of ground shelled corn and soybean meal, and 16%
of a constant concentrate premix. The premix consisted of equal proportions of
corn distillers grains, soybean hulls, expeller soybean meal, vitamins, and
minerals across all diets. Diets contained either no supplemental FS (NFS) or FS
(8.64% RationMate) and either no SU (NSU) or SU (0.61% Ruma Pro) in a 2 x 2
factorial arrangement of treatments. Feeding FS tended to decrease milk
production compared with feeding NFS. Milk fat percentage was increased for cows
fed FS compared with NFS. Feeding SU decreased dry matter intake and increased
feed efficiency compared with cows fed NSU. Dietary treatment had no effect on
energy-corrected milk, milk fat yield, milk protein percentage, or milk urea N.
Feeding FS increased the molar proportion of ruminal butyrate and decreased the
molar proportion of propionate; however, no other effects were observed on
ruminal fermentation. No interactions between FS and SU were observed. It was
concluded that the replacement of corn and soybean meal with dietary FS increased
milk fat percentage and that the replacement of soybean meal with SU
significantly improved feed efficiency.
PMID- 17033028
TI - Rumen lipopolysaccharide and inflammation during grain adaptation and subacute
ruminal acidosis in steers.
AB - Three rumen-fistulated Jersey steers were gradually adapted to a wheat-barley
concentrate over a 4-wk period. Adaptation steps consisted of four 1-wk periods
during which steers were fed diets with forage-to-concentrate (F:C) ratios of
100:0, 79:21, 59:41, and 39:61. The forage consisted of chopped hay (CH), and the
concentrate consisted of pelleted concentrate containing 50% ground wheat and 50%
ground barley. Steers were fed the all-forage diet ad libitum during wk 1. Feed
offered in wk 2 to 4 was kept constant at the ad libitum intake during wk 1. On 2
d that were set 3 d apart during wk 5, subacute ruminal acidosis (SARA) was
induced in the steers by feeding a diet with an F:C ratio of 24:76 by offering
them 0.9 kg of CH at 0900 h followed by 2 meals of 3.0 kg each of wheat-barley
pellets (WBP) at 1100 h and 1300 h and 0.9 kg of CH at 1700 h, to depress rumen
pH for at least 3 h/d below 5.6. The average concentrate inclusion for the SARA
induction diet was 76 +/- 10% DM. During stepwise adaptation, time with pH below
5.6 increased to an average of 121 min/d when the steers were consuming a diet
containing 61% DM as WBP. Dietary inclusion of WBP at the rate of 76% DM induced
SARA because the steers spent an average of 219 min/d with pH below 5.6. The free
ruminal lipopolysaccharide (LPS) concentration increased from 6,310 endotoxin
units (EU)/mL with the all-forage diet to 18,197 EU/mL with the 61% concentrate
diet. The ruminal LPS concentration increased to 26,915 EU/mL when SARA was
induced. Serum haptoglobin increased from 0.53 mg/mL when steers were on the all
forage diet to 1.90 mg/mL with the 61% concentrate diet and were not increased
further by inducing SARA. The serum amyloid-A concentration was not affected by
increasing dietary concentrate during stepwise adaptation to the concentrate, but
increased from 71 to 163 microg/mL when SARA was induced. A gradual increase in
dietary concentrate so that the F:C ratio decreased to 39:61 resulted in
increased ruminal LPS concentrations. Subsequent induction of SARA further
increased ruminal LPS and activated an inflammatory response.
PMID- 17033029
TI - Aberrant low expression level of bovine beta-lactoglobulin is associated with a C
to A transversion in the BLG promoter region.
AB - Beta-lactoglobulin (beta-LG) is the major whey protein in cow's milk. It is well
established that the predominant 2 genetic variants, beta-LG A and B, are
differentially expressed. Extensive investigation of the genetic variation in the
promoter region of the BLG gene revealed the existence of specific haplotypes
associated with the A and B variants, respectively. However, the genetic basis
for the differential expression of BLG A and B alleles is still elusive. We have
previously reported a quantitative beta-LG B variant, characterized by a very low
beta-LG protein expression level. Here, we report that the corresponding BLG
allele (BLG B*) shows a correspondingly low mRNA expression level. Comparative
DNA sequencing of 7,670 bp of the BLG B* allele and the established BLG B allele
revealed a unique difference of a C to A transversion at position 215 bp upstream
of the translation initiation site (g.-215C>A). This mutation segregated
perfectly with the differential phenotypic expression in a paternal half-sib
family and could be confirmed in 2 independent cases. The sequence of the BLG B
allele in the region of the mutation is highly conserved among 4 related ruminant
species. The site of the mutation corresponds to a putative consensus-binding
sequence for the transcription factors c-Rel and Elk-1 as predicted by searching
the TRANSFAC database. The beta-LG B* site might be relevant in the natural
production of milk of low beta-LG content.
PMID- 17033030
TI - Short communication: Genetic analysis of nonreturn rate and mastitis in first
lactation Norwegian Red cows.
AB - Associations between clinical mastitis (CM) and nonreturn rate within 56 d after
first insemination (NR56) were examined in Norwegian Red (NRF) cows. Records on
absence or presence of CM within each of the intervals, -30 to 30, 31 to 150, and
151 to 300 d after first calving, and records on NR56 for 620,492 first-lactation
daughters of 3,064 NRF sires were analyzed with a Bayesian multivariate threshold
liability model. Point estimates of genetic correlations between NR56 and the 3
CM traits were between -0.05 and -0.02. Residual correlations were close to zero,
and correlations between herd-5-yr effects on NR56 and CM in the 3 lactation
intervals ranged from -0.15 to -0.17. It appears that CM and NR56 in first
lactation are independent traits.
PMID- 17033031
TI - Genetics of body condition score in New Zealand dairy cows.
AB - Body condition score (BCS) data were collected on 169,661 first-parity cows from
herds participating in progeny testing schemes and linear type assessment.
Genetic and residual variances for BCS estimated across time using a quadratic
random regression model were found to be largest at the start of lactation.
Heritability estimates ranged from 0.32 to 0.23 from d 1 to 200 of lactation,
with a mean of 0.26. Genetic correlations between BCS and other traits were
estimated using 2 approaches: 1) a multivariate analysis that included BCS and
live weight, both adjusted for stage of lactation; 270-d cumulative yields of
milk, fat, and protein; average somatic cell score; and 2 measures of fertility;
and 2) a bivariate random regression analysis in which BCS was considered to be a
longitudinal trait across time, with the same measurements as in approach 1 for
all other traits. Genetic correlations of BCS with the 2 fertility traits were
0.43 and 0.50 using the multivariate analysis; the corresponding random
regression estimates between BCS as a longitudinal trait across time and 2
measures of fertility were 0.35 to 0.44 and 0.40 to 0.49, and tended to increase
with stage of lactation. Genetic correlations estimated using the random
regression model fluctuated around the multivariate estimates for live weight and
somatic cell score, which were 0.50 and -0.12, respectively. Genetic correlations
estimated using the multivariate analysis of BCS with fat and protein yields were
close to zero. With the random regression model, genetic correlations between BCS
and fat and protein yields were positive at d 1 of lactation (0.16 and 0.08,
respectively) and were negative by d 200 of lactation (-0.25 and -0.20,
respectively). In pastoral production systems, such as those typical in New
Zealand, there appears to be an advantage in the total lactation yields of fat
and protein for cows of higher BCS in early lactation, which is likely to be
because these cows have body reserves that are available to be mobilized in later
lactation, when feed resources are sometimes limited.
PMID- 17033032
TI - Effects of the signal transducer and activator of transcription 1 (STAT1) gene on
milk production traits in Holstein dairy cattle.
AB - A functional candidate gene approach was used to search for genes affecting milk
production traits in Holstein dairy cattle. Signal transducer and activator of
transcription 1 (STAT1) was chosen because of its involvement in the development
of the mammary gland. Using the pooled genomic DNA sequencing approach, we
identified a single nucleotide polymorphism. Genomic DNA was extracted from 1,292
sons obtained from the Cooperative Dairy DNA Repository and from 715 blood
samples of daughters of 12 bulls obtained from the University of Wisconsin
resource population. Daughter yield deviation data for the sons and yield
deviation for the daughters were obtained for milk production traits from the
USDA Animal Improvement Programs Laboratory. For the Repository population,
allele C was associated with significant increases in milk fat and protein
percentages. For the University of Wisconsin population, genotypes CC and CT were
associated with significant increases in milk, fat, and protein yields. Results
from this study are consistent with previous studies on the role of STAT1 in
regulating the transcription of genes involved in milk protein synthesis and fat
metabolism.
PMID- 17033033
TI - Selection for female fertility using censored fertility traits and investigation
of the relationship with milk production.
AB - Bivariate models (censored linear-linear and censored threshold-linear) were used
to estimate genetic parameters for production and fertility traits in the Spanish
Holstein population. Records on 71,217 lactations from 41,515 cows were used: 30
and 36% of lactations were censored for days open (DO) and number of
inseminations to conception (INS), respectively. Heritability estimates for
production traits (milk, fat, protein) ranged between 0.18 and 0.25. Heritability
of days to first service (DFS) and DO was 0.05; heritability of INS on the
liability scale was 0.04. Genetic correlations between fertility traits were
0.41, 0.71, and 0.87 for DFS-INS, DO-INS, and DO-DFS, respectively. Days open had
a larger genetic correlation (ranging from 0.63 to 0.76) with production traits
than did DFS (0.47 to 0.59) or INS (0.16 to 0.23). Greater antagonism between
production and DO may be due to voluntary management decisions for high-yielding
cows, resulting in longer lactation lengths. Inseminations to conception appeared
to be less correlated with milk production than were the other 2 female fertility
traits. Including INS in a total merit index would be expected to increase
genetic gain in terms of profit, but profit would decrease if either DO or DO and
DFS were included in the index. Thus, INS is the trait to be preferred when
selecting for female fertility. The genetic correlation between actual milk yield
and 305-d standardized milk yield was 0.96 in the present study, suggesting that
some reranking of sires could occur. Because the target of attaining a 12-mo
calving interval, as implied by a 305-d standardized lactation length, is
changing in the dairy industry, routine genetic evaluation of actual total
lactation milk yield should be considered.
PMID- 17033034
TI - A structural equation model for describing relationships between somatic cell
score and milk yield in first-lactation dairy cows.
AB - Relationships between production and diseases may involve recursive or
simultaneous effects between traits. Four structural equation models (SEqM) for
somatic cell score and milk yield, with varying specifications for the effects
relating the 2 traits, were compared. Data consisted of repeated records of milk
yield and somatic cell score of 33,453 first-lactation daughters of 245 Norwegian
Red sires that had their first progeny test in 1991 and 1992. All models included
random effects of the sire and of the cow and were fitted using the LISREL
software. The Bayesian information criterion clearly favored a model with a
recursive effect from somatic cell score on milk yield over the 3 other models
fitted (absence of recursive effects; an effect from milk yield on somatic cell
score; simultaneity of effects between the 2 traits). This provides evidence that
the negative association between milk yield and somatic cell score is more likely
due to an effect of infection (measured indirectly by the somatic cell score) on
production than to a dilution effect. Estimates indicated that a mastitis event
would reduce milk yield in the following 15 d by about 900 g/d. The estimated
genetic (co)variances did not change sizably when the specification of recursive
or simultaneous effects was varied. However, estimates of the phenotypic
covariance were altered when a recursive effect from somatic cell score on milk
yield was included in the model.
PMID- 17033035
TI - Detection and characterization of Listeria monocytogenes in Sao Jorge (Portugal)
cheese production.
AB - Listeria monocytogenes is a foodborne pathogen that can cause serious invasive
disease in humans. Because human listeriosis cases have previously been linked to
consumption of contaminated cheese, control of this pathogen throughout the
cheese production chain is of particular concern. To understand the potential for
L. monocytogenes transmission via Sao Jorge cheese, a Portuguese artisanal cheese
variety that bears a Protected Denomination of Origin classification, 357 raw
milk, curd, natural whey starter, and cheese samples representative of the
production chain of this cheese were collected over one year and tested for the
presence of L. monocytogenes and selected physicochemical parameters. Although
neither L. monocytogenes nor other Listeria spp. were detected in whey, curd, or
cheese samples, 2 of the 105 raw milk samples analyzed were positive for L.
monocytogenes. These 2 raw milk isolates represented a ribotype that has
previously been linked to multiple human listeriosis outbreaks and cases
elsewhere, indicating the potential of these isolates to cause human listeriosis.
On average, physicochemical parameters of Sao Jorge cheese ripened for 4 mo
presented values that likely minimize the risk of L. monocytogenes outgrowth
during ripening and storage (mean pH = 5.48; mean moisture = 37.79%; mean NaCl
concentration = 4.73%). However, some cheese samples evaluated in this study were
characterized by physicochemical parameters that may allow growth and survival of
L. monocytogenes. Even though our results indicate that raw milk used for Sao
Jorge cheese manufacture as well as finished products is rarely contaminated with
L. monocytogenes, continued efforts to control the presence of this pathogen in
the Sao Jorge cheese production chain are urged and are critical to ensure the
safety of this product.
PMID- 17033036
TI - Stochastic models for simulating parallel, rotary, and side-opening milking
parlors.
AB - Simulation models of parallel, rotary, and side-opening milking parlors were
built that could predict milking parlor performance according to herd size,
number of milking stalls, labor quality, and cow characteristics. The models were
validated by statistically comparing the duration of the simulated milking
process with actual data collected at 3 dairy farms during 12 mo. Various
scenarios were generated to study parlor performance, and the results indicated
that for a parlor with up to 14 milking stalls, a side-opening design provided
greater capacity than parallel or rotary parlors. Performance of a side-opening
parlor was reduced by enlargement up to 20 milking stalls. For 10 to 40 milking
stalls, a rotary design gave better performance than a double parallel design in
terms of milking process duration and stall utilization. The presented models can
serve as a practical tool in designing new parlors or changing operations of
existing ones.
PMID- 17033037
TI - American Society of Clinical Oncology 2006 update of the breast cancer follow-up
and management guidelines in the adjuvant setting.
AB - PURPOSE: To update the 1999 American Society of Clinical Oncology (ASCO)
guideline on breast cancer follow-up and management in the adjuvant setting.
METHODS: An ASCO Expert Panel reviewed pertinent information from the literature
through March 2006. More weight was given to studies that tested a hypothesis
directly relating testing to one of the primary outcomes in a randomized design.
RESULTS: The evidence supports regular history, physical examination, and
mammography as the cornerstone of appropriate breast cancer follow-up. All
patients should have a careful history and physical examination performed by a
physician experienced in the surveillance of cancer patients and in breast
examination. Examinations should be performed every 3 to 6 months for the first 3
years, every 6 to 12 months for years 4 and 5, and annually thereafter. For those
who have undergone breast-conserving surgery, a post-treatment mammogram should
be obtained 1 year after the initial mammogram and at least 6 months after
completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly
mammographic evaluation should be performed. Patients at high risk for familial
breast cancer syndromes should be referred for genetic counseling. The use of
CBCs, chemistry panels, bone scans, chest radiographs, liver ultrasounds,
computed tomography scans, [18F]fluorodeoxyglucose-positron emission tomography
scanning, magnetic resonance imaging, or tumor markers (carcinoembryonic antigen,
CA 15-3, and CA 27.29) is not recommended for routine breast cancer follow-up in
an otherwise asymptomatic patient with no specific findings on clinical
examination. CONCLUSION: Careful history taking, physical examination, and
regular mammography are recommended for appropriate detection of breast cancer
recurrence.
PMID- 17033038
TI - Number of CD4+ cells and location of forkhead box protein P3-positive cells in
diagnostic follicular lymphoma tissue microarrays correlates with outcome.
AB - PURPOSE: To examine the immune microenvironment in diagnostic follicular lymphoma
(FL) biopsies and evaluate its prognostic significance. PATIENTS AND METHODS:
Immunohistochemistry was used to study numbers and location of cells staining
positive for immune cell markers CD4, CD7, CD8, CD25, CD68, forkhead box protein
P3 (FOXP3), T-cell intracellular antigen-1, and Granzyme B in tissue microarrays
of paraffin-embedded, diagnostic lymph node biopsies taken from 59 FL patients
who lived less than 5 years (short-survival group; n = 34) and more than 15 years
(long-survival group; n = 25). RESULTS: CD4 and FOXP3 expression were
significantly different between the two groups. Samples from the long-survival
group were more likely than those from the short-survival group to have CD4+
staining cells and to have FOXP3-positive cells in a perifollicular location.
CONCLUSION: This study has identified differences in immune cell composition of
the diagnostic FL lymph node immune microenvironment and these have the potential
for use as prognostic biomarkers in a routine histopathology setting.
PMID- 17033039
TI - Phase III trial comparing three doses of docetaxel for second-line treatment of
advanced breast cancer.
AB - PURPOSE: To evaluate whether a relationship exists between docetaxel dose and
clinical response in the treatment of patients with advanced breast cancer.
PATIENTS AND METHODS: Patients whose cancer had progressed after one prior
chemotherapy regimen for advanced breast cancer or had recurred during or within
6 months of adjuvant chemotherapy were randomly assigned to docetaxel 60, 75, or
100 mg/m2 intravenously every 3 weeks. RESULTS: Five hundred twenty-seven
patients were randomly assigned (intent to treat [ITT]), and 524 were assessable
for toxicity. In the population assessable for efficacy (n = 407), logistic
regression analysis showed that increasing docetaxel dose was significantly
associated with higher response rate (P = .007) and improved time to progression
(TTP; P = .014). In the ITT analysis, a significant dose-response relationship
was observed for tumor response (P = .026) but not for TTP (P = .067). The
incidences of most hematologic and nonhematologic toxicities were related to
increasing dose, with grade 3 to 4 neutropenia occurring in 76.4%, 83.7%, and
93.4% and febrile neutropenia occurring in 4.7%, 7.4%, and 14.1% of patients
administered the 60, 75, and 100 mg/m2 doses, respectively. One death was
considered treatment related. CONCLUSION: A relationship between increasing dose
of docetaxel and increased tumor response was observed across the dose range of
60 to 100 mg/m2 every 3 weeks. Toxicities were related to increasing dose.
Depending on the therapy goal, any of the doses studied may be appropriate for
second-line treatment of advanced breast cancer.
PMID- 17033040
TI - A new evaluation method for lumbar spinal instability: passive lumbar extension
test.
AB - BACKGROUND AND PURPOSE: Although many studies have described clinical examination
measures for the diagnosis of lumbar spinal instability, few of them have
investigated the sensitivity and specificity of the measures that were used. The
authors devised a passive lumbar extension (PLE) test for assessing lumbar spinal
instability. The purpose of this study was to investigate the sensitivity,
specificity, and positive likelihood ratio of this test. SUBJECTS AND METHODS:
The PLE test as well as the instability catch sign, painful catch sign, and
apprehension sign tests were done for 122 subjects with lumbar degenerative
diseases. The subjects were divided into 2 groups-instability positive and
instability negative-on the basis of findings on flexion-extension films of the
lumbar spine. The sensitivity, specificity, predictive values, and positive
likelihood ratio of each test were investigated. RESULTS: The sensitivity and
specificity of the PLE test were 84.2% and 90.4%, respectively. These values were
higher than those of other signs. The positive likelihood ratio of the PLE test
was 8.84 (95% confidence interval=4.51-17.33). DISCUSSION AND CONCLUSION: The PLE
test is an effective method for examining patients for lumbar spinal instability
and can be performed easily in an outpatient clinic.
PMID- 17033041
TI - Lengthening the hamstring muscles without stretching using "awareness through
movement".
AB - BACKGROUND AND PURPOSE: Passive stretching is widely used to increase muscle
flexibility, but it has been shown that this process does not produce long-term
changes in the viscoelastic properties of muscle as originally thought. The
authors tested a method of lengthening hamstring muscles called "Awareness
Through Movement" (ATM) that does not use passive stretching. SUBJECTS: Thirty
three subjects who were randomly assigned to ATM and control groups met the
screening criteria and completed the intervention phase of the study. METHODS:
The ATM group went through a process of learning complex active movements
designed to increase length in the hamstring muscles. Hamstring muscle length was
measured before and after intervention using the Active Knee Extension Test.
RESULTS: The ATM group gained significantly more hamstring muscle length (+7.04
degrees ) compared with the control group (+1.15 degrees ). DISCUSSION AND
CONCLUSION: The results suggest that muscle length can be increased through a
process of active movement that does not involve stretching. Further research is
needed to investigate this finding.
PMID- 17033043
TI - D-serine regulation of NMDA receptor activity.
AB - The N-Methyl-D-aspartate-type glutamate receptor (NMDAR) plays a key role in
several important processes involving the nervous system, including brain
development, synaptic plasticity, and learning. Unlike other neurotransmitter
receptors, which are activated by individual neurotransmitters, activation of
NMDARs requires the binding of a coagonist (D-serine or glycine) in addition to
glutamate. Although previously considered an "unnatural" amino acid, D-serine is
a key regulator of NMDAR activity and may be the main physiological ligand at the
coagonist site. D-Serine is synthesized in the mammalian brain and is enriched in
astrocytes, a class of glial cells that ensheath synapses in the brain.
Astrocytes physiologically affect NMDAR neurotransmission by releasing D-serine,
suggesting that D-serine acts as a gliotransmitter. However, recent findings
indicate that D-serine signaling does not depend solely on glia, because D-serine
and its biosynthetic enzyme are also present in substantial amounts in neurons.
Here, we discuss these new findings, which begin to shed light on the relative
roles of glia and neurons in D-serine signaling.
PMID- 17033044
TI - A unified model of the presynaptic and postsynaptic changes during LTP at CA1
synapses.
AB - Long-term potentiation (LTP) has been studied extensively at CA1 synapses of the
hippocampus, and there is evidence implicating both postsynaptic and presynaptic
changes in this process. These changes include (i) addition of AMPA channels to
the extrasynaptic membrane and diffusional equilibrium of extrasynaptic receptors
with synaptic receptors, (ii) sudden addition of AMPA channels to the synapse in
large groups, (iii) a change in the mode of glutamate release (presumably from
kiss-and-run to full fusion), and (iv) a delayed increase in the number of
vesicles released. However, it remains unclear whether (or how) these changes
work together. We have incorporated all of these processes into a structural
model of the synapse. We propose that the synapse is composed of transsynaptic
modules that function quasi-independently in AMPA-mediated transmission. Under
basal conditions, synapses are partially silent; some modules are AMPA-silent
(but contribute to NMDA-mediated transmission), whereas others are functional
(and contribute to both AMPA- and NMDA-mediated transmission). During LTP, there
is both a rapid change in the mode of vesicle fusion and a rapid insertion of a
postsynaptic complex (a hyperslot) containing many proteins (slots) capable of
binding AMPA channels. The combined effect of these pre- and postsynaptic changes
is to convert AMPA-silent modules into functional modules. Slot filling is
transiently enhanced by a rapid increase in extrasynaptic GluR1, a form of the
AMPA-type receptor. A slower transsynaptic growth process adds AMPA-silent
modules to the synapse, enhancing the number of vesicles released and thereby
enhancing the NMDA response. This model accounts for a broad range of data,
including the LTP-induced changes in quantal parameters. The model also provides
a coherent explanation for the diverse effects of GluR1 knockout on basal
transmission, LTP, and distance-dependent scaling.
PMID- 17033045
TI - Molecular signaling mechanisms underlying epileptogenesis.
AB - Epilepsy, a disorder of recurrent seizures, is a common and frequently
devastating neurological condition. Available therapy is only symptomatic and
often ineffective. Understanding epileptogenesis, the process by which a normal
brain becomes epileptic, may help identify molecular targets for drugs that could
prevent epilepsy. A number of acquired and genetic causes of this disorder have
been identified, and various in vivo and in vitro models of epileptogenesis have
been established. Here, we review current insights into the molecular signaling
mechanisms underlying epileptogenesis, focusing on limbic epileptogenesis. Study
of different models reveals that activation of various receptors on the surface
of neurons can promote epileptogenesis; these receptors include ionotropic and
metabotropic glutamate receptors as well as the TrkB neurotrophin receptor. These
receptors are all found in the membrane of a discrete signaling domain within a
particular type of cortical neuron--the dendritic spine of principal neurons.
Activation of any of these receptors results in an increase Ca2+ concentration
within the spine. Various Ca2+-regulated enzymes found in spines have been
implicated in epileptogenesis; these include the nonreceptor protein tyrosine
kinases Src and Fyn and a serine-threonine kinase [Ca2+-calmodulin-dependent
protein kinase II (CaMKII)] and phosphatase (calcineurin). Cross-talk between
astrocytes and neurons promotes increased dendritic Ca2+ and synchronous firing
of neurons, a hallmark of epileptiform activity. The hypothesis is proposed that
limbic epilepsy is a maladaptive consequence of homeostatic responses to
increases of Ca2+ concentration within dendritic spines induced by abnormal
neuronal activity.
PMID- 17033046
TI - Carrot (Daucus carota L.).
AB - Plants are susceptible to infection by a broad range of fungal pathogens. Many
horticulturally important crop species lack adequate genetic resistance to
disease. Studies on potential mechanisms of disease resistance in plants have
revealed the importance of a range of pathogenesis-related (PR) proteins with
antifungal activity in reducing colonization of plant tissues by pathogens. We
are evaluating a range of PR-proteins, through heterologous expression in
transgenic carrot tissues, for their effects on fungal disease development. The
protocols for carrot transformation with a thaumatin-like protein are described.
In addition, the use of herbicide resistance as a selectable marker in carrot
transformation is illustrated. In this protocol, petiole segments from carrot
seedlings are exposed to Agrobacterium for 10-30 min and co-cultivated for 3 d,
after which herbicide selection is imposed until embryogenic calli are produced
after 8-12 wk. The transfer of the embryogenic calli to hormone-free medium
yields transgenic plantlets. This genetic transformation protocol has supported
the generation of transgenic carrot plants with defined T-DNA inserts at the rate
of between 1 and 3 Southern positive independent events out of 100.
PMID- 17033048
TI - Potato (Solanum tuberosum L.).
AB - Potato (Solanum tuberosum L.) is a globally important crop plant producing high
yields of nutritionally valuable food in the form of tubers. It has been the
focus of substantial study because of its use both as a staple food crop and as a
potentially significant source of compounds of interest. This has included the
development and application of transgenic technology for introducing novel traits
of fundamental and applied interest. This chapter describes a rapid, efficient,
and cost-effective system for the routine transformation of this crop plant at
rates above 40% efficiency, calculated as the mean number of Southern blot-
confirmed independent transgenics per number of internodal explants originally
plated. Internodal sections are co-cultivated with Agrobacterium tumefaciens and
subjected to a two-stage callus induction/shoot outgrowth system under kanamycin
selection. Shoot regeneration rates are high using the described method, and
excised independent shoots rooting from the cut end of the stem after two further
subcultures on kanamycin are 95% certain to be transformed. The transgenic status
can be confirmed by molecular analysis and the plants grown on for tuber
production enabling a wide spectrum of further studies.
PMID- 17033047
TI - Cassava (Manihot esculenta Crantz).
AB - During the last three years the generation of stably transformed cassava plants
having value-added traits has become a reality. Currently, two Agrobacterium
mediated transformation systems are routinely used to engineer cassava. These
systems use either somatic embryos or friable embryogenic calli. This paper
presents detailed protocols for the transformation of cassava using primary
somatic embryos. The effects of explant types, tissue culture conditions, and
bacterial and plasmid related factors on transformation efficiency are discussed.
PMID- 17033049
TI - Sweet Potato [Ipomoea batatas (L.) Lam].
AB - Among the available transformation methods reported on sweet potato,
Agrobacterium tumefaciens-mediated transformation is more successful and
desirable. Stem explants have shown to be ideal for the transformation of sweet
potato because of their ready availability as explants, the simple transformation
process, and high-frequency-regeneration via somatic embryogenesis. Under the two
step kanamycin-hygromycin selection method and using the appropriate explants
type (stem explants), the efficiency of transformation can be considerably
improved in cv. Beniazuma. The high efficiency in the transformation of stem
explants suggests that the transformation protocol described in this chapter
warrants testing for routine stable transformation of diverse varieties of sweet
potato.
PMID- 17033050
TI - Bermudagrass (Cynodon spp.).
AB - Bermudagrass is an important warm-season forage and turf species widely grown in
the southern United States. This chapter describes a rapid and efficient protocol
that allows for the generation of a large number of transgenic bermudagrass
plants, bypassing the callus formation phase. Stolon nodes are infected and co
cultivated with Agrobacterium tumefaciens harboring pCAMBIA binary vectors.
Hygromycin phosphotransferase gene (hph) is used as the selectable marker and
hygromycin is used as the selection agent. Green shoots are directly produced
from infected stolon nodes 4 to 5 wk after hygromycin selection. Without callus
formation and with minimum tissue culture, this procedure allowed us to obtain
well-rooted transgenic plantlets in only 7 wk and greenhouse-grown plants in only
9 wk.
PMID- 17033051
TI - Perennial Ryegrass (Lolium perenne L.).
AB - A protocol that facilitates rapid establishment of Agrobacterium-mediated
transformation for perennial ryegrass is described. The synthetic green
fluorescent protein (sgfpS65T) reporter gene is introduced in combination with
the nptII selectable marker gene into axillary bud derived embryogenic calli of
perennial ryegrass (Lolium perenne L.) by co-cultivation with Agrobacterium
tumefaciens strain AGL0 harboring binary vector pYF132. Following the co
cultivation calli are cultured for 48 h in liquid callus medium containing
timentin at 10 degrees C and 70 rpm, which reduces Agrobacterium overgrowth.
Using green fluorescent protein (GFP) as a nondestructive visual marker allows
identification of responsive genotypes and transgenic cell clusters at an early
stage. GFP screening is combined with paromomycin selection to suppress wild type
cells. Transgenic plantlets ready to transfer to soil are obtained within 4 mo of
explant culture. Between 8 and 16% of the Agrobacterium-inoculated calli
regenerate independent, Southern positive transgenic plants. Reproducibility and
efficiency in this perennial ryegrass transformation protocols is controlled by
multiple factors including genotype dependent tissue culture and gene transfer
response, a short tissue culture-and-selection period and the efficient
suppression of Agrobacterium following Agrobacterium-mediated gene transfer.
PMID- 17033052
TI - Switchgrass (Panicum virgatum L.).
AB - During the last decade, Agrobacterium-mediated transformation of more than a
dozen monocotyledonous plants, including forage and turf grasses, has been
achieved. So far, switchgrass is the only warm season grass that has been
transformed with A. tumefaciens. We have developed a highly efficient system for
transformation of different switchgrass explants utilizing the A. tumefaciens
strain AGL1 carrying the binary vector pDM805, containing the phosphinotricin
acetyltransferase (bar) and beta-glucoronidase (GUS) (uidA or gus) genes.
Transformed cultures were selected in the presence of 10 mg/L bialaphos and the
resultant plantlets were treated with the herbicide Basta. The T-DNA delivery
frequency was affected by the genotype, explant used, and the presence or absence
of acetosyringone during inoculation and cocultivation. The total time required
from inoculation to the establishment of plants in soil was 3-4 mo. Stable
integration, expression, and inheritance of both transgenes were confirmed by
molecular and genetic analyses. Approximately 90% of the tested plants appeared
to have only one or two copies of the T-DNA inserts. The transgenes were sexually
transmitted through both male and female gametes to the progeny obtained from
controlled crosses in the expected segregation ratio of 1:1 according to a chi(2)
test at p = 0.05.
PMID- 17033053
TI - Tall Fescue (Festuca arundinacea Schreb.).
AB - Tall fescue (Festuca arundinacea Schreb.) is the predominant cool-season
perennial grass in the United States. It is widely used for both forage and turf
purposes. This chapter describes a protocol that allows for the generation of
large number of transgenic tall fescue plants by Agrobacterium-mediated
transformation. Embryogenic calli induced from caryopsis are used as explants for
inoculation with A. tumefaciens. The Agrobacterium strain used is EHA105.
Hygromycin phosphotransferase gene (hph) is used as the selectable marker and
hygromycin is used as the selection agent. Calli resistant to hygromycin are
obtained after 4-6 wk of selection. Soil-grown tall fescue plants can be
regenerated 4-5 mo after Agrobacterium-mediated transformation.
PMID- 17033054
TI - Turf Grasses.
AB - A reliable and efficient genetic transformation protocol for various turfgrass
species and elite cultivars has been achieved using Agrobacterium tumefaciens. We
describe a general protocol for the establishment of embryogenic cell cultures,
Agrobacterium tumefaciens-mediated transformation, selection, and regeneration of
transgenic turfgrass plants. Embryogenic callus is initiated from mature seeds,
maintained by visual selection, and infected with an Agrobacterium tumefaciens
strain (LBA4404) that contains either an herbicide-resistant bar gene or an
antibiotic-resistant hyg gene driven either by a rice ubiquitin or CaMV35S
promoter. Stable transformation efficiencies up to 43.3% were achieved. Southern
blot and genetic analysis was used to confirm transgene integration in the
turfgrass genomes and normal transmission and stable expression of the transgene
in the T1 generation. We demonstrate herein that five elite cultivars of
bentgrass can be genetically transformed using this single tissue culture media
regime. Additionally, we report the successful Agrobacterium-mediated
transformation of an elite tall fescue variety using minor variations in the same
transformation protocol.
PMID- 17033055
TI - American Elm (Ulmus americana).
AB - American elm (Ulmus americana) is a valuable and sentimental tree species that
was decimated by Dutch elm disease in the mid-20th century. Therefore, any
methods for modifying American elm or enhancing disease resistance are
significant. This protocol describes transformation and tissue culture techniques
used on American elm. Leaf pieces containing the midvein and petiole are used for
explants. Agrobacterium tumefaciens strain EHA105 is used for transformation,
with the binary vector pSE39, containing CaMV35S/nptII as a selectable marker,
ACS2/ESF39A as a putative resistance enhancing gene, and CaMV35S/GUS as a
reporter.
PMID- 17033056
TI - Cork Oak Trees (Quercus suber L.).
AB - A transformation system for selected mature Quercus suber L. trees using
Agrobacterium tumefaciens has been established. Embryos obtained from recurrent
proliferating embryogenic masses are inoculated with AGL1 strain harbouring the
plasmid pBINUbiGUSint, which carries the nptII and uidA genes. Evidence of stable
transgene integration is obtained by polymerase chain reaction for nptII and uidA
genes, Southern blotting and expression of the uidA gene. The transgenic embryos
are germinated and successfully transferred to soil.
PMID- 17033057
TI - Eucalyptus.
AB - Using Eucalyptus camaldulensis as a model system, we describe here a basic
Agrobacterium-mediated genetic transformation protocol through organogenesis for
the production of transgenic plants. Hypocotyl segments or cotyledon pieces from
in vitro seedlings are used as starting materials. The explants are inoculated
and cocultivated with a disarmed, binary strain of A. tumefaciens CIB542
harboring a mini Ti plasmid, pBI121. A modified Gamborg's B5 medium is used as
the basal culture medium throughout stages of co-cultivation, callus induction
and shoot regeneration. The incorporation of neomycin phosphotransferase II
(nptII) and beta-glucuronidase (gus) genes into the plant nuclear genome are
primarily verified by histochemical analysis and polymerase chain reaction (PCR).
Modifications of this protocol to use in mature tissues derived from elite trees
and other Eucalyptus species are also described.
PMID- 17033058
TI - Pine (Pinus radiata).
AB - This chapter describes the transformation of Pinus radiata using organogenic
cotyledon explants rather than the more common somatic embryogenesis methods for
conifers. The advantages of our method are the year round availability of seed
and that over 80% of genotypes can be easily regenerated from the mature
cotyledon explants. The transformation efficiency (i.e., the number of
transformed shoots regenerated from excised cotyledons) is 1.7% and, as with
other Agrobacterium tumefaciens transformation methods, the majority of transgene
integrations are single copy. Critical factors for success are survival of the
cotyledons, Agrobacterium strain, and selection pressure after cocultivation.
PMID- 17033059
TI - Poplar (Populus spp.).
AB - Although species within the genus Populus are, in general, easier to transform
and regenerate in vitro than most other trees, many poplar species are very
recalcitrant. Many protocols that previously have been reported were developed
for a specific genotype or species. Thus, it has often been necessary to re
optimize a protocol each time research is initiated with a new genotype. The
method presented in this chapter has been effective for a wide variety of poplar
genotypes.
PMID- 17033061
TI - Banana (Musa sp.).
AB - Cultivated bananas are vegetatively propagating herbs, which are difficult to
breed because of widespread male and female sterility. As a complementary gene
transfer method in banana, the described Agrobacterium protocol relies on highly
regenerable embryogenic cell cultures. Embryogenic cells are infected and co
cultivated in the presence of acetosyringone with Agrobacterium tumefaciens
harboring a binary plasmid vector to obtain a mixed population of transformed and
untransformed plant cells. Transformed plant cells are promoted to grow for 2 to
3 mo on a cell colony induction medium containing the antibiotics geneticin or
hygromycin as selective agents, while agrobacteria are counterselected by
timentin. The whole procedure, including plant regeneration, takes approx 6 mo
and results in an average frequency of 25 to 50 independent transgenic plants per
plate, which equals 50 mg of embryogenic cells. This method has been applied to a
wide range of cultivars and to generate large populations of transgenic colonies
and plants for tagging genes and promoters in banana.
PMID- 17033060
TI - Rubber Tree (Hevea brasiliensis Muell. Arg).
AB - Rubber tree (Hevea brasiliensis Muell. Arg.) is an important industrial crop for
natural rubber production. At present, more than 9.5 million hectares in about 40
countries are devoted to rubber tree cultivation with a production about 6.5
million tons of dry rubber each year. The world supply of natural rubber is
barely keeping up with a global demand for 12 million tons of natural rubber in
2020. Tapping panel dryness (TPD) is a complex physiological syndrome widely
found in rubber tree plantations, which causes severe yield and crop losses in
natural rubber producing countries. Currently, there is no effective prevention
or treatment for this serious malady. As it is a perennial tree crop, the
integration of specific desired traits through conventional breeding is both time
consuming and labour-intensive. Genetic transformation with conventional breeding
is certainly a more promising tool for incorporation of agronomically important
genes that could improve existing Hevea genotype. This chapter provides an
Agrobacterium-mediated transformation protocol for rubber tree using immature
anther-derived calli as initial explants. We have applied this protocol to
generate genetically engineered plants from a high yielding Indian clone RRII 105
of Hevea brasiliensis (Hb). Calli were co-cultured with Agrobacterium tumefaciens
harboring a plasmid vector containing the Hb superoxide dismutase (SOD) gene and
the reporter gene used was beta-glucuronidase (GUS) gene (uidA). The selectable
marker gene used was neomycin phosphotransferase (nptII) and kanamycin was used
as selection agent. We found that a suitable transformation protocol for Hevea
consists of a 3-d co-cultivation with Agrobacterium in the presence of 20 mM
acetosyringone, 15 mM betaine HCl, and 11.55 mM proline followed by selection on
medium containing 300 mg/L kanamycin. Transformed calli surviving on medium
containing 300 mg/L kanamycin showed a strong GUS-positive reaction. Upon
subsequent subculture into fresh media, we obtained somatic embryogenesis and
germinated plantlets, which were found to be GUS positive. The integration of
uidA, nptII, and HbSOD transgenes into Hevea genome was confirmed by polymerase
chain reaction (PCR) as well as Southern blot analysis.
PMID- 17033062
TI - Citrus.
AB - Since the initial reports on production of transgenic Citrus via Agrobacterium
mediated transformation, significant progress has been made, and many steps of
this procedure using the juvenile tissue explants have been improved. Abundant
availability of starting material and relative simplicity make this procedure an
attractive choice for many researchers despite transformation efficiency that is
in the low range of about 1%. Variety of available Agrobacterium strains and
reporter/selection genes further facilitate the work by allowing careful planning
of experiments in which many steps can be adjusted towards a particular Citrus
cultivar. With the use of this procedure, genetically transformed grapefruit,
oranges, lime, and rootstock cultivars are routinely produced while some
difficulties persist in efforts to transform lemon and especially mandarin
cultivars.
PMID- 17033063
TI - Coffee (Coffea sp.).
AB - Coffee (Coffea sp.) is a perennial plant widely cultivated in many tropical
countries. It is a cash crop for millions of small farmers in these areas. As
compared with other tree species, coffee has long breeding cycles that make
conventional breeding programs time consuming. For that matter, genetic
transformation can be an effective technique to introduce a desired trait in an
already "elite" variety, or to study a gene function and expression. In this
chapter, we describe two Agrobacterium-mediated transformation techniques; the
first with A. tumefaciens to introduce an insect resistance gene and the second
with A. rhizogenes to study candidate gene expression for nematode resistance in
transformed roots.
PMID- 17033064
TI - Papaya (Carica papaya L.).
AB - Transgenic papaya plants were initially obtained using particle bombardment, a
method having poor efficiency in producing intact, single-copy insertion of
transgenes. Single-copy gene insertion was improved using Agrobacterium
tumefaciens. With progress being made in genome sequencing and gene discovery,
there is a need for more efficient methods of transformation in order to study
the function of these genes. We describe a protocol for Agrobacterium-mediated
transformation using carborundum-wounded papaya embryogenic calli. This method
should lead to high-throughput transformation, which on average produced at least
one plant that was positive in polymerase chain reaction (PCR), histochemical
staining, or by Southern blot hybridization from 10 to 20% of the callus clusters
that had been co-cultivated with Agrobacterium. Plants regenerated from the
callus clusters in 9 to 13 mo.
PMID- 17033065
TI - Pineapple [Ananas comosus (L.) Merr].
AB - A procedure for pineapple [Ananas comosus (L.) Merr.] genetic transformation is
described, which involves temporary immersion bioreactors (TIB) for selection of
transgenic plants. Success in the production of transgenic pineapple plants
combines tissue culture factors. Firstly, the use of regenerable pineapple callus
as starting material for transformation whose cells shown to be competent for
Agrobacterium infection. Secondly, the used of filtered callus, resulting in
homogeneously sized clusters, thereby increasing the contact between the cell
surfaces and A. tumefaciens and releasing phenolic compounds which induce
Agrobacterium virulence. Thirdly, regeneration of primary plants without
selection pressure, that allowing a massive production of putative transgenic
pineapples. Finally, we support that TIB technology is a powerful system to
recover nonchimera transgenic plants by micropropagation with the use of an
adequate selection agent.
PMID- 17033066
TI - Sugarcane (Saccharum spp.).
AB - We describe the procedures for recovering transgenic sugarcane from co
cultivation of both calli and in vitro plants with Agrobacterium tumefaciens. The
correct tissue culture strategies and the use of super-binary vector or super
virulent strain are crucial for the successful sugarcane transformation. Both
plant regeneration via calli culture and micropropagation strategies can be
optimized to a wide spectrum of sugarcane genotypes, thus the procedures
presented here could be applied to genetic engineering of Saccharum spp. after
minor modifications. For the case of sugarcane transformation using in vitro
plants, four selective micropropagation steps must be sufficient to eliminate
chimera plants.
PMID- 17033067
TI - American Chestnut [Castanea dentata (Marsh.) Borkh].
AB - The key to successful transformation of American chestnut is having the correct
combination of explant tissue, selectable and scorable markers, and a reliable
regeneration system. Rapidly dividing somatic embryos, growing as proembryogenic
masses, are a suitable tissue; the bar gene is a suitable selectable marker in
conjunction with 1.0 to 10 mg/L phosphirothricin (PPT); and the mgfp5-ER gene is
an effective nondestructive scorable marker. We have also found that the more
gently the somatic embryos are treated during the inoculation and co-cultivation
steps, the higher the transformation efficiency. The average transformation
efficiency that can be expected using the described protocol is approx 20 stable
and embryogenic transformation events/g of somatic embryo tissue. Cell line and
batch-to-batch deviations both upward and downward should be expected. Finally,
somatic embryos can be induced to form shoots, which can then be micropropagated
and acclimatized.
PMID- 17033068
TI - Apple (Malus x domestica).
AB - Apple (Malus x domestica) is one of the most consumed fruit crops in the world.
The major production areas are the temperate regions, however, because of its
excellent storage capacity it is transported to distant markets covering the four
corners of the earth. Transformation is a key to sustaining this demand -
permitting the potential enhancement of existing cultivars as well as to
investigate the development of new cultivars resistant to pest, disease, and
storage problems that occur in the major production areas. In this paper we
describe an efficient Agrobacterium tumefaciens-mediated transformation protocol
that utilizes leaf tissues from in vitro grown plants. Shoot regeneration is
selected with kanamycin using the selectable kanamycin phosphotransferase
(APH(3)II) gene and the resulting transformants confirmed using the scorable uidA
gene encoding the bacterial beta-glucuronidase (GUS) enzyme via histochemical
staining. Transformed shoots are propagated, rooted to create transgenic plants
that are then introduced into soil, acclimatized and transferred to the
greenhouse from where they are taken out into the orchard for field-testing.
PMID- 17033069
TI - Blueberry (Vaccinium corymbosum L.).
AB - Recent advances in plant biotechnology have led to a reliable and reproductive
method for genetic transformation of blueberry. These efforts built on previous
attempts at transient and stable transformation of blueberry that demonstrated
the potential of Agrobacterium tumefaciens-mediated transformation, and as well,
the difficulties of selecting and regenerating transgenic plants. As a
prerequisite for successful stable transformation, efficient regeneration systems
were required despite many reports on factors controlling shoot regeneration from
leaf explants. The A. tumefaciens-mediated transformation protocol described in
this chapter is based on combining efficient regeneration methods and the results
of A. tumefaciens-mediated transient transformation studies to optimize selected
parameters for gene transfer. The protocol has led to successful regeneration of
transgenic plants of four commercially important highbush blueberry cultivars.
PMID- 17033070
TI - Grapevine (Vitis vinifera L.).
AB - Grapevine (Vitis) is considered to be one of the major fruit crops in the world
based on hectares cultivated and economic value. Grapes are used not only for
wine but also for fresh fruit, dried fruit, and juice production. Wine is by far
the major product of grapes and the focus of this chapter is on wine grape
cultivars. Grapevine cultivars of Vitis vinifera L. have a reputation for
producing premium quality wines. These premium quality wines are produced from a
small number of cultivars that enjoy a high level of consumer acceptance and are
firmly entrenched in the market place because of varietal name branding and the
association of certain wine styles and regions with specific cultivars. In light
of this situation, grapevine improvement by a transgenic approach is attractive
when compared to a classical breeding approach. The transfer of individual traits
as single genes with a minimum disruption to the original genome would leave the
traditional characteristics of the cultivar intact. However, a reliable
transformation system is required for a successful transgenic approach to
grapevine improvement. There are three criteria for achieving an efficient
Agrobacterium-mediated transformation system: (1) the production of highly
regenerative transformable tissue, (2) optimal co-cultivation conditions for both
grapevine tissue and Agrobacterium, and (3) an efficient selection regime for
transgenic plant regeneration. In this chapter, we describe a grapevine
transformation system which meets the above mentioned criteria.
PMID- 17033071
TI - Strawberry (Fragaria x ananassa).
AB - Genetic transformation in strawberry (Fragaria spp.) can be achieved by using the
Agrobacterium-mediated procedure on leaves from in vitro proliferated shoots.
Regardless of the sufficient regeneration levels achieved from leaf explants of
some commercial strawberry genotypes, the regeneration of transformed strawberry
plants remains difficult and seems to be strongly genotype dependent. In fact,
the main factors that play an important role in the success of strawberry genetic
transformation are the availability of both an efficient regeneration protocol
and an appropriate selection procedure of the putative transgenic shoots. The
strawberry genetic transformation protocol herein described relates to two
genotypes resulting from our experience with the highest regeneration and
transformation efficiency. The study includes an octoploid Fragaria x ananassa
cultivar (Sveva) and a diploid F. vesca cultivar (Alpina W.O.). All the different
steps related to the leaf tissue Agrobacterium infection, co-culture, and
selection of regenerating adventitious shoots, as well as the following
identification of selected lines able to proliferate and root on the selective
agent (kanamycin), will be described.
PMID- 17033072
TI - Walnut (Juglans).
AB - Walnut species are important nut and timber producers in temperate regions of
Europe, Asia, South America, and North America. Trees can be impacted by
Phytophthora, crown gall, nematodes, and cherry leaf roll virus; nuts can be
severely damaged by codling moth and Xanthomonas blight. The long-generation time
of walnuts and an absence of identified natural resistance for most of these
problems suggest biotechnological approaches to crop improvement. Described here
is a somatic embryo based transformation protocol that has been used to
successfully insert horticulturally useful traits into walnut. Selection is based
on the combined use of the selectable neomycin phosphotransferase (nptII) gene
and the scorable uidA gene. Transformed embryos can be germinated or
micropropagated and rooted for plant production. The method described has been
used to establish field trials of mature trees.
PMID- 17033073
TI - Carnation (Dianthus caryophylus L.).
AB - Carnation is a valuable crop for the cut flower industry and demand for new and
improved varieties is growing. However, genetic transformation of carnations is
currently limited because of a lack of efficient routine technique. In this
chapter, we present an easy and effective protocol for gene transfer to carnation
node explants and subsequent adventitious shoot regeneration. For high
adventitious shoot regeneration, node explants from first to third node of 5- to
8-cm long shoots were cultured on Murashige and Skoog (MS) medium, containing 1.0
mg/Lthidiazuron (TDZ), 0.1 mg/L alpha-napthalenoacetic acid (NAA), 20 g/L
sucrose, and 2 g/L Gellan gum for 10 d. Then the explants were cut into 8 radial
segments and subcultured onto MS medium, containing 1.0 mg/L BA, 0.1 mg/L NAA, 20
g/L sucrose and 2 g/L Gellan Gum. For effective genetic transformation, 3- to 5-d
precultured node explants were submerged in an Agrobacerium suspension for 10
min, then cocultivated on filter paper soaked with water and 50 microM
acetosyringone (AS). After cocultivation, the explants were cut into eight radial
segments and subcultured onto selection medium until transformed shoots
regenerated from the explants.
PMID- 17033074
TI - Chrysanthemum (Dendranthema x grandiflora).
AB - This chapter provides reproducible methods for the transformation of Dendranthema
x grandiflora 'Shuhou-no-chikara' (standard) and 'Lineker' (spray) stem internode
thin cell layers (TCLs) and conventional stem internode explants using
Agrobacterium strains carrying a binary vector with beta-glucoronidase (GUS)
reporter and nptII selector genes. Transformation efficiencies are reported at
the kanamycin selection (callus formation and plantlet rooting), GUS assay,
polymerase chain reaction (PCR), and Southern analysis levels. Notes on
regeneration improvement through the use of TCLs, as well as the effective use of
sonication for both regeneration and generation of transformants, stimulation of
Agro-infection and elimination of Agrobacterium, are included.
PMID- 17033075
TI - Orchids (Cymbidium spp., Oncidium, and Phalaenopsis).
AB - Recent advances in genetic engineering have made the transformation and
regeneration of plants into a powerful tool for orchid improvement. This chapter
presents a simple and reproducible Agrobacterium tumefaciens-mediated
transformation protocol and molecular screening technique of transgenics for two
orchid species, Oncidium and Phalaenopsis. The target tissues for gene transfer
were protocorm-like bodies (PLBs) derived from protocorms, into which constructed
foreign genes were successfully introduced. To establish stable transformants,
two stages of selection were applied on the PLBs co-cultivated with A.
tumefaciens. About 10% transformation efficiency was achieved in Oncidium orchid,
as 108 antibiotic resistant independent PLBs were proliferated from 1000 infected
PLBs. In Phalaenopsis orchid about 11 to 12% of transformation efficiency was
achieved by using the present protocol. Different molecular methods and GUS
staining used to screen putative transgenic plants to confirm the integration of
foreign DNA into the orchid genome were also described in detail. The methods
described would also be useful for transformation of desired genes into other
orchid species.
PMID- 17033076
TI - Petunia (Petunia hybrida).
AB - Petunia hybrida genetic transformation continues to be a valuable tool for
genetic research into biochemical pathways and gene expression, as well as
generating commercial products with varying floral colors. In this chapter, we
describe a simple and reproducible genetic transformation protocol for generating
transgenic petunia plants harboring a gene of interest and selectable marker. The
system utilizes Agrobacterium tumefaciens for transgene integration with plant
recovery via shoot organogenesis from leaf explant material. Selection for
transgenic plants is achieved using the bar gene conferring resistance to
glufosinate or nptII gene for resistance to kanamycin. Transformation
efficiencies of around 10% are achievable with shoots being recovered about 8 wk
after transgene insertion and rooted plants transferred to the greenhouse about
twelve weeks after inoculation.
PMID- 17033077
TI - Rose (Rosa hybrida L.).
AB - Although rose transformation is successful, it remains difficult to transform
myriad rose species as well as different rose genotypes. In this protocol, a
detailed description of rose transformation is presented. This protocol relied on
Agrobacterium-mediated transfer of embryogenic callus cultures. There are many
critical steps that must be followed to achieve successful transformation;
however, it is important to keep in mind that these apply to a selected number of
genotypes, and as a different genotype is subjected to transformation,
modifications of this protocol must be made to achieve successful transformation.
PMID- 17033078
TI - Ginseng (Panax ginseng).
AB - Genetic transformation is an attractive way to improve Panax ginseng C. A. Meyer
by introducing new genetic materials and altering metabolic pathways that
regulating the production of secondary compounds. In P. ginseng, production of
transgenic plants via Agrobacterium tumefaciens is performed via somatic
embryogenesis using cotyledon or embryogenic callus as explants. This chapter
introduces the protocol of A. tumefaciens mediated-genetic transformation in P.
ginseng.
PMID- 17033079
TI - Hemp (Cannabis sativa L.).
AB - Hemp (Cannabis sativa L.) suspension culture cells were transformed with
Agrobacterium tumefaciens strain EHA101 carrying the binary plasmid pNOV3635. The
plasmid contains a phosphomannose isomerase (PMI) selectable marker gene. Cells
transformed with PMI are capable of metabolizing the selective agent, mannose,
whereas cells not expressing the gene are incapable of using the carbon source
and will stop growing. Callus masses proliferating on selection were screened for
PMI expression using a chlorophenol red assay. Genomic DNA was extracted from
putatively transformed callus lines and the presence of the PMI gene was
confirmed using polymerase chain reaction and Southern hybridization. Using this
method, an average transformation frequency of 31.23% +/- 0.14 was obtained for
all transformation experiments, with a range of 15.1 to 55.3%.
PMID- 17033080
TI - Opium Poppy (Papaver somniferum).
AB - The genetic transformation of opium poppy, Papaver somniferum, offers the
opportunity to study the mechanisms involved in the regulation of
benzylisoquinoline and morphinan alkaloid biosynthesis. The development of an
efficient transformation protocol for opium poppy has allowed us to transform a
range of genotypes from all around the world, including previously recalcitrant
high-yielding commercial Australian cultivars. The method involves Agrobacterium
tumefaciens infection of hypocotyl explants, followed by the production of
antibiotic or herbicide resistant embryogenic callus, the subsequent induction of
somatic embryos and development into normal plants. The use of different
selective agents, binary vectors, and poppy genotypes has demonstrated the
robustness and reliability of this protocol in the production of many hundreds of
confirmed transgenic poppies.
PMID- 17033081
TI - Actinomycetes (Streptomyces lividans).
AB - Agrobacterium tumefaciens is best known for its ability to transform plants by
delivering the T-DNA that is processed and transferred from the resident Ti
plasmid to the recipient plant cells. Less well known is the capacity of this
Gram-negative bacterium to transfer its T-DNA into fungi and actinomycetes.
Procedures are described on the use of the promiscuous T-DNA transfer system of
A. tumefaciens to transform members of the actinomycetes. Integration of the T
DNA derivatives into the Streptomyces chromosome provides opportunities of
obtaining valuable mutants of this antibiotic producing soil organism.
PMID- 17033082
TI - Filamentous Fungi (Magnaporthe grisea and Fusarium oxysporum).
AB - A better understanding of fungal biology will facilitate judicious use of
beneficial fungi and will also advance our efforts to control pathogenic fungi.
Molecular studies of fungal biology have been greatly aided by transformation
mediated mutagenesis techniques. Transformation via nonhomologous integration of
plasmid DNA bearing a selectable marker (e.g., antibiotic resistance gene) has
been widely used for the random insertional mutagenesis of fungi - as an
alternative to chemical and radiation mutagens - mainly because the integration
of plasmid into the genome provides a convenient tag for subsequent
identification and isolation of the mutated gene. Homologous recombination
between a target gene on the chromosome and the introduced DNA carrying its
mutant allele results in targeted gene knock-out. An important advance in fungal
transformation methodology is the development of Agrobacterium tumefaciens
mediated transformation (ATMT) protocols for fungi. ATMT has been successfully
applied to a phylogenetically diverse group of fungi and offers a number of
advantages over conventional transformation techniques in both the random
insertional mutagenesis and targeted gene knock-out. In this chapter, we describe
ATMT protocols and vectors for fungal gene manipulation using two plant
pathogenic fungi, Magnaporthe grisea and Fusarium oxysporum, as target organisms.
PMID- 17033083
TI - Green Alga (Chlamydomonas reinhardtii).
AB - This protocol describes the Agrobacterium tumefaciens-mediated nuclear
transformation of a microalgae Chlamydomonas reinhardtii, using a gene construct
carrying the genes coding for beta-glucuronidase (gus), green fluorescent protein
(gfp), and hygromycin phosphotransferase (hpt). The transformation frequency with
this protocol as revealed by hygromycin resistance was many fold higher (about 50
fold) than that of the commonly used glass bead method of transformation. The
simplicity of Agrobacterium-mediated gene transfer and the high transformation
frequency as well as the precision of T-DNA integration will enable further
molecular dissection of this important model organism as well as other algal
systems to understand basic plant metabolic processes as well as to exploit the
systems for biotechnological applications.
PMID- 17033084
TI - Mammalian cells.
AB - Agrobacterium most likely can transform virtually all known plant species, and
experimental protocols for Agrobacterium-mediated genetic transformation of yet
more plant species, ecotypes, and cultivars are published almost on a daily
basis. Interestingly, the Agrobacterium host range is not limited to the plant
kingdom, and it has been shown to transform many species of fungi and even
prokaryotes. The ability of Agrobacterium to genetically transform HeLa cells
further widens the range of potential hosts of Agrobacterium to include humans
and perhaps other animal species. Furthermore, because mammalian cells
significantly differ from plant cells, they provide a useful experimental system
for identification and functional characterization of plant-specific factors
involved in the transformation process. Here, we present basic procedures for
transfection and Agrobacterium-mediated genetic transformation of mammalian
cells. We also demonstrate the use of mammalian cells for studies of the cellular
components of the genetic transformation pathway.
PMID- 17033085
TI - Mushroom (Agaricus bisporus).
AB - We have devised an easy and effective genetic transformation method for the
preeminent edible mushroom, Agaricus bisporus. Our method exploits the T-DNA
transfer mechanism in Agrobacterium tumefaciens and relies on the reproductive
fruiting body as the recipient tissue. The use of fruiting body explants,
particularly the gill, provided high-frequency transformation, overcoming the
inefficacy of Agrobacterium-based methods targeting fungal spores or vegetative
mycelium. The protocol entails incubation of A. tumefaciens for 3 h with
acetosyringone, a signaling molecule that launches the gene transfer mechanism,
co-cultivation of the induced bacterium and gill explants for 3 d, and selection
for transformants based on an inherited resistance to the antibiotic hygromycin.
Between 7 and 28 d on the selection medium, upwards of 95% of the gill explants
generate hygromycin-resistant colonies. About 75% of the mushroom transformants
show a single-copy of the hygromycin-resistant gene integrated at random sites in
the genome.
PMID- 17033086
TI - Yeast (Saccharomyces cerevisiae).
AB - The yeast Saccharomyces cerevisiae is one of the best characterized eukaryotic
organisms. This species has enabled a detailed study of the (genetic)
requirements for Agrobacterium-mediated DNA transformation. For instance research
with this yeast has led to the recognition that the transforming DNA molecules
integrate into the eukaryotic chromosomes either by homologous recombination,
which is the preferred pathway in S. cerevisiae, or by nonhomologous end-joining.
Based on the protocol for Agrobacterium-mediated transformation of S. cerevisiae
methodology has been developed for the transformation of many other yeast and
fungal species.
PMID- 17033087
TI - Potential involvement of a propranolol-insensitive atypical beta-adrenoceptor the
vasodilator effect of cyanopindolol in the human pulmonary artery.
AB - The aim of our study was to examine whether non beta(1)-/beta(2)-adrenoceptors
participate in the relaxation of the human pulmonary artery. For this purpose the
vasodilatory effect of the non-conventional partial beta-adrenoceptor agonist
cyanopindolol was examined. Cyanopindolol (1-300 microM), studied in the presence
of the beta(1)-/beta(2)-adrenoceptor antagonist propranolol, relaxed the human
pulmonary artery preconstricted with serotonin 1 microM in a concentration
dependent manner (maximally by about 80%). This effect was diminished by
bupranolol 10 microM (an antagonist of beta(1)-beta(3)-adrenoceptors and the low
affinity state of the beta(1)-adrenoceptor) and CGP 20712 10 microM (known to
antagonize the low-affinity state of the beta(1)-adrenoceptor at high
concentrations). In further experiments, the effect of beta-adrenoceptor ligands
on the serotonin-induced vasoconstriction was examined. The concentration
response curve for serotonin was not affected by cyanopindolol 30 microM,
bupranolol 10 microM and CGP 20712 10 microM but shifted to the right by
cyanopindolol 100 and 300 microM; the serotonin 5-HT(2A) receptor antagonist
ketanserin 0.3 microM abolished the maximum contraction elicited by serotonin. In
conclusion, the present study reveals that the vasodilatory effect of
cyanopindolol in the human pulmonary artery consists of two components, i.e.
activation of a propranolol-insensitive atypical beta-adrenoceptor and antagonism
against 5-HT(2A) receptors.
PMID- 17033088
TI - Cerebroprotective effect of angiotensin IV in experimental ischemic stroke in the
rat mediated by AT(4) receptors.
AB - Recent studies have reported potential roles of angiotensins in an adaptative
physiological mechanism of protection against cerebral ischemia-induced
neurological damages. In the present study, we examined the protective role of
angiotensin IV (AngIV) in a rat model of embolic stroke induced by intracarotid
injection of calibrated microspheres (50 microm). Internal carotid infusions of
increasing doses of AngIV (0.01, 0.1 and 1 nmol/0.1 mL saline) dose dependently
decreased mortality, neurological deficit and cerebral infarct size at 24 hours.
With the highest dose of AngIV, mortality was reduced from 55 % in saline infused
controls to 10 % (p=0.003), neurological deficit was reduced from 3.8 +/- 0.3 to
1.4 +/- 0.3 , (p<0.0001) and cerebral infarct size at 24 hours was decreased from
432 +/- 26 mm(3) to 185 +/- 19, (p=0.0001). The AT(4) antagonist divalinal-AngIV
(10(-9) mol/0.1 mL), or pretreatment with L-NAME (10(-7) mol/0.1 mL), both
completely abolished the protective effect of AngIV (1 nmol). The AT(2)
antagonist PD123319 (10(-7) mol/0.1 mL) partially prevented the protective effect
of AngIV on the neurological score. Sequential cerebral arteriographies revealed
that AngIV induced a redistribution of blood flow to the ischemic areas within
minutes. These results suggest that pharmacological doses of AngIV are protective
against acute cerebral ischemia by triggering an AT(4)-mediated, NO-dependent
intracerebral hemodynamic mechanism.
PMID- 17033089
TI - Increased reactive oxygen species contributes to kidney injury in
mineralocorticoid hypertensive rats.
AB - Hypertension is associated with increased reactive oxygen species (ROS). Renal
ROS production and their effects on renal function have never been investigated
in mineralocorticoid hypertensive rats. In this study we hypothesized that
increased ROS production in kidneys from deoxycorticosterone (DOCA)-salt rats
contributes to adverse renal morphological changes and impaired renal function in
DOCA-salt hypertensive rats. We also determined whether ROS-induced renal injury
was dependent on blood pressure. DOCA-salt hypertensive rats exhibited a marked
increase in blood pressure, renal ROS production, glomerular and tubular lesions,
and microalbuminuria compared to sham rats. Treatment of DOCA-salt hypertensive
rats with apocynin for 28 days resulted in attenuation of systolic blood pressure
and improvement of renal morphology. Renal superoxide level in DOCA-salt rats was
215% of sham-operated rats and it was significantly decreased to 140% with
apocynin treatment. Urinary protein level was decreased from 27 +/- 3 mg/day in
DOCA-salt hypertensive rats to 9 +/- 2 mg/day. 28 days of Vitamin E treatment
also reduced renal injury in regard to urinary protein level and renal morphology
but had no effect on blood pressure in DOCA-salt rats. Increased urinary 8
isoprostane, a marker for oxidative stress, in DOCA-salt hypertensive rats (55 +/
8 ng/day) was diminished by vitamin E treatment (24 +/- 6 ng/day). These data
suggest that renal injury characteristic of mineralocorticoid hypertension is
associated with oxidative stress and is partly independent of blood pressure.
PMID- 17033090
TI - Inhibitory effect of Ca(2+) on ATP-mediated stimulation of NPR-A-coupled guanylyl
cyclase in renal glomeruli from spontaneously hypertensive and normotensive rats.
AB - Atrial natriuretic peptide (ANP) regulates blood pressure mainly through the
occupation of the guanylyl cyclase-coupled receptor NPR-A, which requires ATP
interaction for maximal activation. This study investigates the effect of
extracellular Ca(2+) on ATP-mediated regulation of NPR-A-coupled guanylyl cyclase
activity in glomerular membranes from Wistar Kyoto (WKY) and spontaneously
hypertensive rats (SHR). ATP induced a significant increase in basal and ANP(1
28)-stimulated guanylyl cyclase activity that was greater in SHR than in WKY.
Extracellular Ca(2+) inhibited ATP-stimulated guanylyl cyclase activity in a
concentration-dependent manner, but did not modify basal and ANP(1-28)-stimulated
guanylyl cyclase activity. In the presence of ATP, NPR-A showed higher affinity
for ANP(1-28) and lower Bmax. Ca(2+) did not modify NPR-A-ANP(1-28) binding
properties. The different effects of extracellular Ca(2+) on ANP(1-28)- or ATP
mediated guanylyl cyclase activation suggest that these events are differentially
regulated. Addition of extracellular Ca(2+) induced similar effects in
hypertensive and normotensive rats, suggesting that it is not responsible for the
elevated cGMP production observed in SHR.
PMID- 17033091
TI - Upregulation of angiotensin AT1a receptors mRNA in the heart and renal medulla
after myocardial infarction in rats.
AB - The myocardial infarct causes prolonged activation of the renin-angiotensin
system and profoundly influences cardiac performance and renal excretory
capabilities. The aim of the present study was to determine whether the
myocardial infarct is also associated with an altered expression of AT1a
receptors (AT1aR) mRNA in the heart and the kidney. To this end male Sprague
Dawley rats were subjected either to the left coronary artery ligation or to the
sham surgery. Four weeks after the surgery the animals were sacrificed. In 11
infarcted and 10 sham-operated rats expression of AT1aR mRNA in the walls of the
left and right ventricle of the heart, and in the renal cortex and renal medulla
was determined by semiquantitative PCR method. In another group of 10 infarcted
and 14 sham-operated rats the diameter of cardiomyocytes in the left and right
cardiac ventricle was determined. The size of the infarct in the rats used for
mRNA determination and for morphometric measurements was equal to 29.4 +/- 1.8%
and to 31.0 +/- 1.2 % of the left ventricular wall, respectively. Expression of
AT1aR mRNA was significantly greater in the left (P< 0.01) and right ventricle
(P<0.03) of the heart in the infarcted than in the sham operated rats. AT1aR mRNA
expression was also significantly greater (P<0.02) in the renal medulla of the
infarcted rats than in the renal medulla of the sham operated rats whereas no
significant difference was found in the renal cortex. The myocardial infarct was
associated with a significant increase of diameter of cardiomyocytes of the left
ventricle of the heart (P< 0.0001), however there was no significant correlation
between changes in AT1aR mRNA expression and diameter of cardiomyocytes. The
results provide evidence that the myocardial infarct results in significant and
prolonged upregulation of AT1a receptors mRNA expression in the heart and in the
medullary region of the kidney.
PMID- 17033092
TI - Imipramine and citalopram reverse corticosterone-induced alterations in the
effects of the activation of 5-HT(1A) and 5-HT(2) receptors in rat frontal
cortex.
AB - Using extracellular recording we studied changes in the reactivity of rat frontal
cortical slices to the 5-HT(1A), 5-HT(2) and 5-HT(4) receptor agonists, (+/-)-2
dipropyloamino-8-hydroxy-1,2,3,4-tetrahydronaphtalene hydrobromide (8-OH-DPAT),
(+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and zacopride,
respectively, induced by an earlier treatment of animals with corticosterone
lasting 1 or 3 weeks. Spontaneous bursting activity was recorded in ex vivo
slices incubated in a medium devoid of Mg(2+) ions and containing picrotoxin (30
microM). Repetitive, but not single, corticosterone administration resulted in an
attenuation of the effect of the activation of 5-HT(1A) receptors and in an
enhancement of the effect related to 5-HT(2) receptors. The effect of 5-HT(4)
receptor activation remained unchanged. In separate two sets of experiments rats
were treated with corticosterone for 3 weeks and additionally with imipramine or
citalopram, beginning on the eighth day of corticosterone administration. In the
corticosterone plus imipramine as well as corticosterone plus citalopram groups
the effects of 8-OH-DPAT and DOI were not different from control indicating that
corticosterone-induced functional modifications in the reactivity of 5-HT(1A) and
5-HT(2) receptors were reversed by antidepressant treatments.
PMID- 17033094
TI - Effects of tyrosine kinase inhibitors on voltage-dependent Ba(2+) currents in the
guinea-pig gastric antrum.
AB - We have investigated whether tyrosine kinases modify the activity of voltage
dependent Ba(2+) currents (I(Ba)) recorded from guinea-pig gastric myocytes by
use of patch-clamp techniques. All experiments were carried on single smooth
muscle cells, dispersed from the circular layer of the guinea-pig gastric antrum.
Genistein ( > or = 10 microM), a specific tyrosine kinase inhibitor, reduced the
peak amplitude of I(Ba) in a voltage- and concentration-dependent manner.
Daidzein ( > or = 30 microM), an inactive analog of genistein, also inhibited
I(Ba) in a concentration-dependent manner. Similarly, other types of tyrosine
kinase inhibitors (lavendustin A and tyrphostin 23) suppressed the peak amplitude
of I(Ba) in a concentration-dependent manner. These results indicate that
tyrosine kinases may be essential to regulate Ca(2+) mobilization through voltage
dependent Ca(2+) channels in gastric myocytes.
PMID- 17033093
TI - Comparison of gene expression profiles in neuropathic and inflammatory pain.
AB - Molecular mechanisms underlying the differences between chronic neuropathic and
inflammatory pain are still poorly understood. Identifying those differences
should provide insight into the molecular mechanism underlying features unique
for neuropathic pain, such as allodynia. We have performed screening for
differentially expressed genes in the spinal cord in the rat models of
neuropathic and inflammatory pain. Using BD Atlas Rat 4K arrays we found several
differences in expression of secretion-related genes between inflammatory and
neuropathic pain. Development of the latter was characterized by up-regulated
expression of genes associated with immune response and microglia activation and
also, to a lesser extent, with cytoskeleton rearrangement. The relative increase
in abundance of four genes, intercellular adhesion molecule 1 (ICAM-1),
calcitonin gene related peptide (CGRP), tissue inhibitor of metalloproteinase 1
(TIMP-1), chemokine-like receptor 1 was confirmed by reverse transcription Real
Time PCR (qPCR) validation in the spinal cord in neuropathic pain. Levels of
transcripts corresponding to ICAM-1 and TIMP-1 were also increased in the dorsal
root ganglia (DRG) of neuropathic rats. Our data point at the importance of
immune response- and microglia activation-related genes in the development of
chronic neuropathic pain, and suggest that expression of CGRP gene in the dorsal
horn of the spinal cord could be involved in persistence of its symptoms.
PMID- 17033095
TI - Influence of ghrelin on gastric and duodenal growth and expression of digestive
enzymes in young mature rats.
AB - Ghrelin, a nature ligand for the growth hormone secretagogue receptor (GHS-R),
stimulates a release of growth hormone, prolactin and adrenocorticotropic
hormone. Also, ghrelin increases food intake in adult rats and humans and
exhibits gastroprotective effect against experimental ulcers induced by ethanol
or stress. The aim of present study was to examine the influence of ghrelin
administration on gastric and duodenal growth and expression of pepsin and
enterokinase in young mature rats with intact or removed pituitary. METHODS: Two
week after sham operation or hypophysectomy, eight week old Wistar male rats were
treated with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose) i.p. twice a
day for 4 days. Expression of pepsin in the stomach and enterokinase in the
duodenum was evaluated by real-time PCR. RESULTS: In animals with intact
pituitary, treatment with ghrelin increased food intake, body weight gain and
serum level of growth hormone and insulin-like growth factor-1 (IGF-1). These
effects were accompanied with stimulation of gastric and duodenal growth. It was
recognized as the significant increase in gastric and duodenal weight and mucosal
DNA synthesis. In both organs, ghrelin administered at the dose of 8 nmol/kg
caused maximal growth-promoting effect. In contrast to these growth-promoting
effects, administration of ghrelin reduced expression of mRNA for pepsin in the
stomach and was without effect on expression of mRNA for enterokinase in the
duodenum. Hypophysectomy alone lowered serum concentration of growth hormone
under the detection limit and reduced serum level of IGF-1 by 90%. These effects
were associated with reduction in daily food intake, body weight gain and
gastroduodenal growth. In hypophysectomized rats, administration of ghrelin was
without significant effect on food intake, body weight gain or growth of
gastroduodenal mucosa. Also, serum concentration of growth hormone or IGF-1 was
not affected by ghrelin administration in rats with removed pituitary.
CONCLUSION: Administration of ghrelin stimulates gastric and duodenal growth in
young mature rats with intact pituitary, but inhibits expression of mRNA for
pepsin in the stomach. Growth hormone and insulin-like growth factor-1 play an
essential role in growth-promoting effects of ghrelin in the stomach and
duodenum.
PMID- 17033096
TI - Opioid agonist/antagonist effect of naloxone in modulating rabbit jejunum
contractility in vitro.
AB - Opioid peptides are the most effective drugs in controlling pain; their action is
elicited by binding to specific membrane receptors. The gastrointestinal tract
represents, after the nervous system, the site in which the opioid receptors are
expressed at high levels. The opioid agonist morphine has a significant
inhibitory effect on intestinal motility, this action is blocked by naloxone an
opioid antagonist mainly active at mu and kappa receptors. In this study the
presence of mu opioid receptor on rabbit jejunum was investigated by western
blot. The effects of beta-endorphin, the endogenous opioid peptide with the
highest affinity to the mu opioid receptor and those of naloxone on spontaneous
rabbit jejunum contractions were evaluated. Beta-endorphin (10(-6) M) showed a
relaxant effect on jejunum contractility while naloxone showed a dual effect
inducing an increase of spontaneous contractility at low concentrations (10(-6)
M, 10(-7) M, 10(-8) M) and a decrease when high concentrations (10(-3) M, 10(-4)
M, 10(-5) M) were utilized. The obtained results demonstrate that mu opioid
receptor is expressed in rabbit jejunum and suggest that this receptor may be
involved in mediating the effects of both opioid agonist and antagonist on
jejunum contractions.
PMID- 17033097
TI - Angiotensins II and IV modulate adrenocortical cell proliferation in
ovariectomized rats.
AB - Effects of angiotensins II (AngII), angiotensin IV (AngIV, 3-8 fragment of
angiotensin II) and losartan (an antagonist of angiotensin receptor type 1) on
the proliferation of adrenocortical cells in ovariectomized rats have been
studied. The incorporation of bromodeoxyuridine (BrdU) into cell nuclei was used
as an index of cell proliferation. AngIV decreased BrdU labeling index mainly in
the reticularis zone and losartan (Los) was able to partially reverse this
inhibitory effect of AngIV. AngII had no effect on the adrenocortical cell
proliferation when given alone, however Los given simultaneously diminished BrdU
incorporation into nuclei of glomerulosa and reticularis zones as compared with
AngII. These findings suggest that AngII and AngIV modulate adrenocortical cell
proliferation in ovariectomized rats.
PMID- 17033098
TI - The involvement of nitric oxide and prostaglandins in the cholinergic stimulation
of hypothalamie-pituitary-adrenal response during crowding stress.
AB - The aim of the present study was to determine the effect of social crowding
stress and significance of nitric oxide (NO) and prostaglandins (PG) generated by
constitutive and inducible nitric oxide synthase (NOS) and cyclooxygenase (COX)
in the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic
muscarinic receptor agonist carbachol. Inhibitors of neuronal NOS (nNOS) L-NNA,
general NOS L-NAME and inducible NOS (iNOS) aminoguanidine, as well as inhibitors
of COX-1, piroxicam, and COX-2, compound NS-398 were administered 15 min prior to
carbachol to control or crowded rats (24 rats in cage for 7, during 3 and 7
days). In stressed rats L-NAME, L-NNA and aminoguanidine significantly
intensified the carbachol-induced ACTH and corticosterone secretion, like in
control rats. Piroxicam, markedly decreased the carbachol-induced ACTH and
corticosterone response under either basal or stress conditions. Compound NS-398
did not markedly alter the carbachol-induced HPA response in control and stressed
rats. Crowding stress (3 days) significantly impaired the i.c.v. prostaglandin
E(2)-induced ACTH response. Corticotropin releasing hormone (CRH) receptor
antagonists, alpha-helical CRH [9-14], given i.c.v. did not alter the PGE(2)
evoked corticosterone response in either control or stressed rats, indicating
that hypothalamic CRH is not involved in the PGE(2)-induced central stimulation
of HPA axis. In control rats L-NAME considerably enhanced, while L-arginine, a
physiological NOS substrate, abolished the PGE(2)-induced ACTH and corticosterone
response. In stressed rats this NOS blocker significantly increased and L-Arg
reduced the stimulatory effect of PGE(2) on ACTH and corticosterone secretion.
The carbachol-induced corticosterone response was significantly increased by
pretreatment with nNOS inhibitor L-NNA and was considerably reduced by
indomethacin, a general COX inhibitor. Pretreatment with both antagonists left
the carbachol-induced corticosterone level unchanged, suggesting an independent
and reciprocal effect of NO and PG in the cholinergic stimulation of pituitary
adrenocortical response. These results indicate that in the stimulatory action of
muscarinic agonist, carbachol, NO is an inhibitory transmitter under basal and
crowding stress conditions. This psychosocial stress does not functionally affect
the NOS/NO systems. Prostaglandins are involved in the cholinergic muscarinic
induced stimulation of HPA response to a significant extent in non-stressed rats.
PGE(2) may be involved in the carbachol-elicited HPA response under basal and
stress conditions. Prostaglandins released in response to muscarinic stimulation
did not evoke the hypothalamic CRH mediation. NO significantly impairs and PG
stimulates the carbachol-induced HPA response in rats under basal and social
stress conditions.
PMID- 17033099
TI - The expression of short from of leptin receptor gene during early pregnancy in
the pig examined by quantitative real time RT-PCR.
AB - The study was conducted to determine gene expression of short form of leptin
receptor (OB-Rs) using real time RT-PCR in distinct tissues of the central
nervous system (medial basal hypothalamus, preoptic area, stalk median eminence),
pituitary and reproductive tract (corpus luteum, ovarian stroma, endometrium,
myometrium, and trophoblast) in pigs during luteal phase of the cycle and early
gestation. The expression of OB-Rs mRNA in SME did not differ between analyzed
stages of the cycle and pregnancy. In anterior pituitary, transcript levels were
almost identical in mid- and late-luteal periods, but significantly decreased on
30-32 day of gestation when compared with day 14-16. In posterior pituitary,
significantly higher expression was observed in two periods of pregnancy when
compared with two stages of luteal phase. In corpus luteum the lowest expression
was observed during days 10-12 of the cycle, whereas markedly higher levels were
detected in late-luteal stage and gestation. In ovarian stroma the expression of
Ob-Rs mRNA was markedly diminished during days 14-16 of the cycle when compared
with days: 10-12 of the cycle and 30-32 of pregnancy. The expression of Ob-Rs
mRNA in endometrium and myometrium reached the lowest levels on 30-32 day of
pregnancy in comparison with earlier stage, 14-16 day. Summarizing, the
expression of the short form of leptin receptor mRNA was found in majority of
tested tissues including hypothalamus, pituitary and reproductive tract and their
levels fluctuated depending on the phase (mid- and late-luteal) of the cycle and
the day of pregnancy (early and late stage of implantation).
PMID- 17033100
TI - Interspecies differences in the force-frequency relationship of the medial
gastrocnemius motor units.
AB - Single, functionally isolated motor units were studied in the medial
gastrocnemius (MG) muscle of cats and rats. Axons of their motoneurons were
stimulated with trains of pulses at frequencies increasing from 1 to 150 Hz and
forces developed by muscle fibers were measured and force-frequency curves were
compared between species. The following observations were made: (1) the most
steep parts of curves (related to unfused tetani of motor units) begun at lower
frequencies of stimulations in all types of feline motor units, (2) for fast
motor units, the same relative values of force of unfused tetani were achieved at
significantly lower frequencies of stimulations in the cat than in the rat.
Twitch time parameters of both species influenced the course of force-frequency
curves. It was showed that the contraction times of feline units varied in the
wide range (21-81 ms), and these units reached 60% of the maximum force at
stimulation frequencies between 10 and 38 Hz. On the other hand, contraction
times of rat units ranged from 10 to 34 ms, whereas stimulation frequencies
necessary to reach 60% of the maximum force varied considerably, from 12 to 65
Hz. The correlations between the above parameters were found for motor units of
each species. However, the regression lines drown for the collected population of
cat and rat units did not form linear continuity. Thus it seems that interspecies
differences in the twitch contraction times do not fully explain different force
frequency relationships in mammalian skeletal muscles.
PMID- 17033102
TI - Helicobacter pylori: microbiology and interactions with gastrointestinal
microflora.
AB - Helicobacter pylori causes substantial morbidity and mortality, and the course of
infection results from complex interactions between host, environmental and
bacterial factors. It is generally accepted that H. pylori eradication is the
best method of treatment for peptic ulcer disease and prevention of its
complications. However, the antimicrobial agents used in eradication regimens
cause various alterations in gastrointestinal microflora, which can lead to side
effects affecting the patient's compliance. Moreover, antimicrobial therapy is
responsible for increasing resistance not only in H. pylori but also in
colonising microflora, and, therefore, alternative approaches to the treatment
and prevention of H. pylori infection have been investigated.
PMID- 17033103
TI - Interplay between Helicobacter pylori and the immune system. Clinical
implications.
AB - Helicobacter pylori (H. pylori) is a gram-negative bacteria infecting more than
50% of human population. H. pylori selectively colonizes gastric mucosa and
represents the major cause of gastroduodenal pathologies, such as gastric ulcer,
autoimmune gastritis, gastric cancer and B cell lymphoma of mucosa associated
lymphoid tissue (MALT). In this review interplay between H. pylori and both
innate and adaptive immune responses is discussed. The second part of this
article presents current knowledge about the relationship between H. pylori
infection and neoplasia.
PMID- 17033104
TI - Helicobacter pylori and its involvement in gastritis and peptic ulcer formation.
AB - Modern gastroenterology started in early 19(th) century with the identification
by W. Prout of the inorganic (hydrochloric) acid in the stomach and continued
through 20(th) century with the discoveries by I.P. Pavlov of neuro-reflex
stimulation of gastric secretion for which he was awarded first Nobel Prize in
1904. When concept of nervism or complete neural control of all digestive
functions reached apogeum in Eastern Europe, on the other side of Europe (in
United Kingdom), E. Edkins discovered in 1906 that a hormone, gastrin, may serve
as chemical messenger in stimulation of gastric acid secretion, while L.
Popielski revealed in 1916 that histamine is the most potent gastric
secretagogue. K. Schwartz, without considering neural or hormonal nature of
gastric secretory stimulation, enunciated in 1910 famous dictum; "no acid no
ulcer"; and suggested gastrectomy as the best medication for excessive gastric
acid secretion and peptic ulcer. In early 70s, J.W. Black, basing on earlier L.
Popielski's histamine concept, identified histamine-H(2) receptors (H(2)-R) and
obtained their antagonists, which were found very useful in the control of
gastric acid secretion and ulcer therapy for which he was awarded in 1972 second
Nobel Prize in gastrology. With discovery by G. Sachs in 1973 of proton pumps and
their inhibitors (PPI), even more effective in gastric acid inhibition and ulcer
therapy than H(2)-R antagonists, gastric surgery, namely gastrectomy, practiced
since first gastric resection in 1881 by L. Rydygier, has been considered
obsolete for ulcer treatment. Despite of the progress in gastric pharmacology,
the ulcer disease remained essentially "undefeated" and showed periodic
exacerbation and relapses. The discovery of spiral bacteria in the stomach in
1983 by B.J. Marshall and R.J. Warren, Australian, clinical researches, awarded
in 2005 the Nobel Prize for the third time in gastrology, has been widely
considered as a major breakthrough in pathophysiology of gastritis and peptic
ulcer, which for the first time can be definitively cured by merely eradication
of germ infecting stomach. This overview presents the mechanism of induction of
gastritis and peptic ulcer by the H. pylori infection and describes accompanying
changes in gastric acid and endocrine secretion as well as the effects of germ
eradication on gastric secretory functions and gastroduodenal mucosal integrity.
PMID- 17033105
TI - Gastric cancer and Helicobacter pylori infection.
AB - The Nobel prize in Physiology and Medicine in 2005 was presented to Barry
Marshall and Robin Warren for their discovery of Helicobacter pylori (Hp), but
only the involvement of this germ in gastritis and peptic ulcer has been
mentioned in the award sentence, while numerous epidemiological, clinical and
experimental studies and reports emphasized the crucial role of Hp in
pathogenesis of gastric cancer (GC). This review is based on the old concept
proposed by P. Correa much before the discovery of spiral bacteria in the
stomach, postulating the cascade of mucosal changes from acute/chronic gastritis
into the atrophic gastritis with intestinal metaplasia and finally to dysplasia
and GC. It is now widely accepted view that Hp infection is the major initiator
of the inflammatory and atrophic changes in gastric mucosa accompanied by an over
expression of certain growth factors such as gastrin as well as of cyclooxygenase
2 (COX-2) and anti-apoptotic proteins including survivin and B-cl(2), leading to
proliferation of mutated atrophic cells, excessive angiogenesis, inhibition of
apoptosis and formation of gastric tumour. All the morphological and biochemical
changes associated with the transformation of mucosal cells into the cancer cells
can be traced in excellent experimental model of gastric cancerogenesis induced
by infection of Hp in Mongolian gerbils. Since the eradication therapy was proved
in several prospective clinical trials to greatly reduce the incidence of GC and
this was confirmed on the gerbil model of Hp-induced GC, it has been postulated;
a) that Hp is the major causal factor in pathogenesis of GC and b) that the only
rational approach in attempt to reduce the occurrence of GC is the global
eradication of Hp.
PMID- 17033106
TI - Interaction of nonsteroidal anti-inflammatory drugs (NSAID) with Helicobacter
pylori in the stomach of humans and experimental animals.
AB - Helicobacter pylori (H. pylori) and non-steroidal anti-inflammatory drugs (NSAID)
are major pathogenic factors in peptic ulcer disease but whether these two
factors exert synergistic or antagonistic action on the gastric mucosa has been a
subject of controversy. The classic concept states that there is an increased
ulcer occurrence and bleeding in patients with both H. pylori infection and NSAID
use. However, the question whether the H. pylori eradication therapy in NSAID
users reduces the occurrence of peptic ulcer has not been fully addressed.
Studies on secondary prevention of NSAID-associated ulcers in H. pylori patients
have indicated that H. pylori eradication results in impaired ulcer healing with
an effect on the rate of peptic ulcer occurrence. On the other hand, the
treatment of H. pylori in patients with no prior history of chronic NSAID therapy
has been shown to decrease the risk of peptic ulcer. Studies in experimental
animals revealed for instance, that the H. pylori infection augments the gastric
mucosal damage induced by NSAID in Mongolian gerbils. In rats with preexisting
chromic gastric ulcers, H. pylori infection attenuated significantly the aspirin
induced inhibition of ulcer healing and accompanying fall in the gastric blood
flow at the margin of these ulcers, suggesting negative interaction between
aspirin and H. pylori on ulcerogenesis. Accumulated evidence in humans and
animals shows that both aspirin and H. pylori upregulate the expression of
cyclooxygenase (COX)-2 both at mRNA and protein levels at the ulcer margin, but
failed to influence significantly that of COX-1. It was, therefore, proposed that
H. pylori may in fact, antagonize, aspirin-induced delay of ulcer healing due to
suppression of acid secretion by the enhancement in PGE(2) possibly derived from
COX-2 expression and activity and to the overexpression of growth factors such as
TGF alpha and VEGF. The present review summarizes and further addresses the issue
of the interaction between these two major ulcer risk factors determined in the
stomach of humans and experimental animals.
PMID- 17033107
TI - Helicobacter pylori infection in pathogenesis of gastroesophageal reflux disease.
AB - Gastroesophageal reflux disease (GERD) refers to the very common and constantly
increasing conditions where reflux of gastric contents into the esophagus leads
to development of characteristic symptoms. The esophagus, LES and stomach can be
envisioned as single functional unit controlled by neuro-hormonal factors. The
abnormalities that contribute to GERD can start in any component of this unit,
resulting particularly from disturbances in their control system. It is extremely
important to identify factors and mechanisms leading to functional failure of
this system so that causative therapy can be effectively applied. The key-role
has been attributed to parasympathetic dysfunction, which may adversely affect
motor activity of this area by increasing transient LES relaxation number and
impairing LES pressure, esophageal acid clearance and motility of the proximal
stomach. Recently, numerous investigations have been performed to elucidate the
role of Helicobacter pylori (Hp) infection in GERD pathogenesis with the most
concern given to its potency to increase gastric acid secretion. However, it
appeared that this infection leads to much more complex changes in gastric mucosa
including modification of afferent neural signals and specific gastric hormones
release. Plasma ghrelin level is low in subjects infected and increases
significantly after eradication. Since ghrelin, beside potency to increase
gastric secretion has strong prokinetic action on LES functional unit, this
phenomenon together with impaired vagal control may contribute to the Hp
infection or eradication - related GERD development. Thus, ghrelin and vagal
activity could be the missing links that partially explains relationship between
GERD and Hp infection.
PMID- 17033108
TI - The relationship between the presence of Helicobacter pylori in the oral cavity
and gastric in the stomach.
AB - There are numerous studies suggesting that inflammation of the oral cavity caused
by bacteria or fungi is accompanied by gastric inflammation. This is particularly
relevant in patients using complete dentures. Since the presence of H. pylori in
the oral cavity can be easily discovered by bacteria culture and that in the
stomach by (13)C urea breath test (UBT) and histology of gastric endoscopic
biopsy samples it is reasonably to state that the majority of the patients show
the presence of bacterium in oral cavity and active gastric H. pylori infection.
When comparing, however, the bacteria culture originating from the oral mucosa to
those from the gastric mucosa, employing molecular biology examination, such as
polymerase chain reaction (PCR), we found that the oral bacteria and those
originating from stomach are completely different, suggesting that H. pylori may
be present only transiently in oral cavity and does not play major role in
gastric H. pylori infection. Thus, oral cavity does not serve as bacterial
reservoir to infect gastric mucosa. Most important finding of our study is that
patients with recognized inflammation in the oral cavity in the form of
stomatitis prothetica hyperplasica both fibrosa as well as papillaris showed in
nearly 100% gastric H. pylori infection, usually without the presence of the same
bacterium in the oral cavity, suggesting that gastric H. pylori infection affects
oral mucosa at distance by some, as yet, unknown mechanism.
PMID- 17033109
TI - Helicobacter pylori infection in coronary artery disease.
AB - The role of inflammation in the pathogenesis and progression of coronary artery
disease (CAD) has been increasingly discussed, but still remains unclear.
Inflammatory changes in the vessel wall play an important role in the
pathogenesis of atherosclerosis. Systemic inflammatory reaction can be detected
by showing increased plasma levels of different proinflammatory cytokines and
acute-phase proteins. Infectious agents have been linked to coronary heart
disease on epidemiological and pathogenetic grounds. The prevalent condition and
the exact mechanism of initiation of atherosclerotic vascular disease remain
unclear. Nevertheless, many similarities exist between the processes of
inflammation and atherogenesis, and the evidence is growing for the role of an
active inflammation in the atherosclerosis in the coronary circulation and
elsewhere. Although the seroepidemiological and eradication studies have
suggested a causal relationship between Helicobacter pylori (Hp) infection and
coronary heart disease; the issue is still controversial. The detection of Hp
specific DNA in atheromatous plaque material from coronary arteries, but more
important, the reduction in restenosis of coronary vessels after Hp eradication
could be interpreted as an evidence for the involvement of a Hp infection in the
progression of CAD induced by a local inflammatory process.
PMID- 17033110
TI - Frequency of Helicobacter pylori infection in children under 4 years of age.
AB - The work aimed at establishment of frequency of Helicobacter pylori (Hp)
infection in children under 4 years of age. One hundred ninety-eight children (6
month to 4 year) were tested using urea breath test (UBT) with the non
radioactive isotope (13)C (50 mg of urea). The air was collected before and in
the 20(th) and 30(th) minute after standard meal. The results of measurements
(mass spectrometry IRMS) were given as a quotient (13)CO(2)/CO(2) (delta), and a
positive value was set at delta>3,5%. Parents of tested children were asked to
fill in a questionnaire on a somatic development, the digestive tract symptoms of
a child and family members as well as socioeconomic conditions. The data were
analyzed to establish the risk factors in Hp infection in children. Hp infection
was found in 18,38% of children. It was not related to child's sex nor age. The
statistical significance was found in the occurrence of Hp infection among
children whose family members had infection and among those attending creches or
kindergartens. Non-radioactive (13)C UBT is very useful and easy method to use in
epidemiological studies even in youngest children. The course of infection was
asymptomatic and had no impact on their somatic development. Factors increasing
the risk of Hp infection were occurrence of Hp among other family members and
contact with other children in educational facilities.
PMID- 17033112
TI - Guidelines in the medical treatment of Helicobacter pylori infection.
AB - Scientific evidence based on controlled clinical research confirm substantial
benefits resulting from the eradication of H. pylori infection in such
pathologies of the alimentary tract as: gastric peptic and duodenal ulcer (active
or confirmed in the future and ulcer disease complications), MALT (Mucosa
Associated Limphoid Tissue) lymphoma, atrophic gastritis, past stomach resection,
gastric cancer in the family. The above group of indications is strongly
recommended for eradicative treatment. During the last several years there have
been many guidelines made by international and national specialist groups. "Test
and treat" strategy of undiagnosed dyspepsia treatment is based on possibility to
carry out non-invasive tests confirming H. pylori infection. First symptoms of
dyspepsia in people over 45 years of age constitute recommendation for endoscopy,
as well as symptoms assumed to be "alarming" (loss of weight, anaemia, bloody
vomiting, tarry stool, dysphagia) regardless of patient age. An individual
approach to eradication is proposed in gastroesophageal reflux disease, and use
of non-steroid anti-inflammatory drugs. Antibacterial activity towards H. pylori
is shown by many antibiotics (amoxicillin, macrolides, tetracyclines) and some
other chemotherapeutic agents (nitroimidazoles) and bismuth. PPIs are
recommended, because through increase of pH in stomach they create conditions to
act for antibiotics. During the stage of first line triple therapy, it is advised
to apply PPI and two antibacterial medicines at the same time (PPI +
amoxicillin+metronidazole or clarithromycin). Such therapeutic action ensures
achievement of eradication of H. pylori infection in 80-90% of cases. In case of
lack of treatment efficiency in the first-line therapy, 7-14 day treatment may be
repeated using triple therapies (PPI + 2 antibiotics) substituting the antibiotic
with the metronidazole or tetracycline, or quadruple therapies (PPI + bismuth
citrate + 2 antibiotics). Side effects during eradicative treatments occur quite
rarely (from 15 to 30%).
PMID- 17033111
TI - Efficacy of Helicobacter pylori eradication taking into account its resistance to
antibiotics.
AB - The discovery of Helicobacter pylori (H. pylori) provided a possibility to cure
effectively patients with peptic ulcers. Recent studies have shown varying
susceptibility of H. pylori strains to antibiotics and increasing resistance to
some of the recommended drugs. The purpose of the present study was to evaluate
the efficacy of the currently recommended eradication schemes and to assess the
increasing resistance of H. pylori strains to recommended antibiotics.
Furthermore, the effect of probiotics (Lacidofil) on the efficacy of first-line
treatment with amoxicillin and clarithromycin was analyzed. The study population
consisted of 641 patients: 192 received amoxicillin with clarithromycin and
proton pump inhibitor (PPI), 241 - tetracycline, tinidazole, bismuth and PPI, 53
amoxicillin with clarithromycin and PPI supplemented with Lacidofil. The
efficacy of eradication treatment was evaluated by the (13)C-urease breath test.
The microbiological examination included 111 samples of H. pylori. The present
study demonstrated low efficacy of the tetracycline, tinidazole, bismuth and PPI
scheme i.e. 71.4%, moderate efficacy of the amoxicillin with clarithromycin and
PPI scheme i.e. 85.9%, whereas the supplementation with Lacidofil significantly
increased the efficacy of eradication to 94.3%. The microbiological examination
revealed a relatively high level of primary resistance to clarithromycin (22.2%)
and a high level to metronidazole (46.7%), with no resistance to amoxicillin.
However, the most important finding is the high level of secondary resistance to
clarithromycin and metronidazole (more than 66% in both cases). The present
findings suggest the need for modification of the recommended eradication
schemes.
PMID- 17033113
TI - Helicobacter pylori in liver diseases.
AB - At the present stage of knowledge, the participation of the Helicobacter bacteria
in the pathology of liver and the bile tract in humans has not been univocally
documented. However, apparent are the premises so as to go on performing the
examinations under discussion since the said participation cannot be excluded. If
the more direct evidence of the etiologic role of the Helicobacter in the
pathology of liver were available, it would create the chances for the more
effective treatment of patients than the case has been so far. Cancer commonly
derives from the chronic inflammation and infection and in case of hepatocellular
carcinoma (HCC), may arise either from local liver derived progenitor cells
(LPCs) or bone marrow originated stem cells (BMSCs) and future studies should
disclose the role of either type of cells and of inflammatory factors such as
generated by Helicobacter infection in the liver pathophysiology.
PMID- 17033114
TI - Indian Academy of Pediatrics and polio eradication in India.
PMID- 17033115
TI - Hypertonic saline treatment in children with cerebral edema.
AB - OBJECTIVE: To compare the efficacy and side effects of hypertronic saline and
mannitol use in cerebral edema. DESIGN: Retrospective study. SETTING: Pediatric
intensive care unit. SUBJECTS: 67 patients with cerebral edema. METHODS: Patients
with cerebral edema treated with either mannitol or hypertronic saline (HS)
(Group II: n = 25), and both mannitol and HS (Group III: n = 20) were evaluated
retrospectively. Cerebral edema and increased intracranial pressure were based on
the clinical and/or radiological (CT, MR) findings. When treating with both
mannitol and HS (Group IIIA), if patients serum osmality was greater than 325
mosmol/L, mannitol was stopped and patients were treated with only HS (Group
IIIB). All patients were closely monitored for fever, pulse, blood pressure,
central venous pressure (CVP), oxygen saturation, volume of fluid intake and
urine output. Mannitol was given at a dose of 0.25-0.5 g/kg while the hypertonic
saline was given as 3% saline to maintain the serum-Na within the range of 155
165 mEq/L. RESULTS: There was no statistically significant difference in terms of
Glasgow coma scale, age, gender, and etiologic distribution between the groups.
And also distribution of the other treatments given for cerebral edema is not
significiant. Mannitol was given for a total dose of 9.3 +/-5.0 (2-16) doses in
Group I, and 6.5 +/-2.8 (2-10) doses in Group III. Hypertonic saline was infused
for 4-25 times in Group II. Although there was no statistically significant
difference in the highest serum Na and osmolarity levels of the groups, duration
of comatose state and mortality rate were significantly lower in Group II and
Group III A B. Patients who received only HS were subdivided according to their
serum Na concentrations into 2 groups as those between 150-160 mEqL and those
between 160-170 mEqL. The duration of comatose state and mortality was not
different in patients with serum-Na of 150-160 mEqL and in patients with 160-170
mEqL in the hypertonic saline receiving patients. Four patients in the group II
developed hyperchloremic metabolic acidosis and 2 patients in the group I had
hypotension. As two patients in group II had diabetes insipidus and one patient
had renal failure in group I, the treatment was terminated. The causes of death
were septic shock, ventilator associated pneumonia with acute respiratory
distress syndrome, progressive cerebral edema and cerebral edema with pulmonary
edema. Multivariate analysis showed that age, gender, cause of cerebral edema,
electrolyte imbalance, hyperglycemia and hyper-ventilation had no significant
impact on outcome. CONCLUSION: Hypertonic saline seems to be more effective than
mannitol in the cerebral edema.
PMID- 17033116
TI - Efficacy and safety of montelukast as monotherapy in children with mild
persistent asthma.
AB - OBJECTIVE: To study the efficacy and tolerability of montelukast as monotherapy
in the treatment of mild persistent bronchial asthma. DESIGN: Open, non
comparative, prospective, 12-month study. SETTING: Asthma clinic in urban multi
speciality trust hospital. METHODS: Children (age 3-11 yrs) with mild persistent
asthma, not on any prophylactic drugs were enrolled consecutively (from January
to December 2003) and started on 4 mg (2-4 yrs) or 5mg (<4 yrs) montelukast for a
period of 12 weeks. Efficacy was assessed by improvements in clinical score, peak
expiratory flow rates (PEFR), spirometry measurements and reduction in reliever
drug requirement after 4 and 12 weeks of therapy. Side effects were also judged
after 12 weeks of therapy. RESULTS: 50 children (mean age 5.41 +/-2.11 years)
completed the study. There was association with positive family history (92%),
allergic rhinitis (64%), exercise induced asthma (40%), cough variant asthma
(24%), seasonal asthma (80%) and high IgE (12%) levels. Clinical scores, viz,
activity, wheeze and cough, improved effectively from (1.64 +/-0.5253) at
baseline to (0.7 +/-0.7071) and (1.72 +/-0.701) to (0.92 +/-0.6952) and (1.5 +/
0.6145) to (0.88 +/-0.8241) respectively after 12 weeks of therapy. Significant
clinical improvement (p >0.001) was also noted after 4 weeks of therapy. Peak
expiratory flow rates (done in 19 cases) documented improvement from (120.21 +/
12.23) at baseline to (135.41 +/-23.34) after 12 weeks. FEV1 / FVC (done in 11
cases) improved from (71.44 +/-1.35%) to (87.10 +/-8.34%) after 12 weeks. Mean
improvement in all the parameters demonstrated P value less than >.001. A total
of 19 of 50 cases showed mild side-effects as anorexia (16%), elevated liver
function tests (18%) and headache (10%). CONCLUSION: The clinical outcome showed
significant improvement (p < 0.01) after 4 and 12 weeks.
PMID- 17033117
TI - Epilepsy, antiepileptic drugs and educational problems.
AB - Epilepsy is a chronic disorder that significantly affects learning and behavior.
Children with epilepsy are particularly vulnerable to educational problems and
resultant academic underachievement. Co-morbidities like cognitive and behavioral
problems contribute significantly for the problems at school. Both epilepsy and
neuropsychological deficits may occur as different clinical manifestations of a
common etiological process. Ongoing seizures themselves adversely affect the
developing brain. Furthermore, psychosocial issues also contribute significantly
to the problems at school. The effect of antiepileptic drugs is double edged in
this setting. They may reduce the seizure burden and thus improve the cognitive
function. However, these drugs also significantly affect the learning process.
The treating pediatrician should be equipped to comprehensively address all these
factors for an optimal outcome. Recent onset of educational problems in a child
with epilepsy deserves immediate and aggressive evaluation and management.
PMID- 17033118
TI - The recurring coma epidemic in children in India: what is it?
PMID- 17033119
TI - Clinical profile and morbidity pattern of infants born to HIV infected mothers in
Durban South Africa.
AB - This study describes the clinical characteristics and co-infections in infants
born to HIV infected women being followed up in a high risk clinic of South
Africa Sixty three percent (302 out of 476) of mothers attended clinic for
varying periods during follow-up. Sixty four per cent of babies had physical
clinical signs suggestive of HIV infection. In the majority of babies, persistent
signs resolved by 9 months of age. In those with persistent signs, 20 percent
tested positive for HIV infection. Among the HIV exposed infants, co-infections
with TB, CMV, syphilis and Herpes zoster were diagnosed which appeared
independent of their ultimate seroconversion status.
PMID- 17033120
TI - Serum zinc levels in newborns with neural tube defects.
AB - Neural tube defects (NTD) comprise of a group of congenital malformations that
include spina bifida, anencephaly and encephalocele. Reports have implicated zinc
deficiency as one of the causative factors of NTDs. We compared the serum zinc
level of 23 newborns having neural tube defects with 35 healthy controls by
spectrophotometery during 2003-2004. Zinc deficiency was documented in 43.5% of
the cases and 8.6% of the controls (P = 0.002). Multivariate logistic regression
analysis revealed a significant association between the presence of NTDs and zinc
deficiency (OR = 8.2, 95% Cl: 1.9-34.7).
PMID- 17033121
TI - Detection of parvovirus B19 in a case of erythema infectiosum with myositis.
AB - A well documented case of erythema infectiosum is being reported here for the
first time from India which was associated with myositis that has not been
reported globally. A 9-year-old child presented with moderate to high grade
fever, mild anemia, and erythematous rash involving face, trunks and limbs
associated with arthralgia, myalgia and myositis. Parvovirus B19 infection was
confirmed by detection of IgM antibodies (inhouse ELISA) and DNA (nested PCR) in
patient's serum.
PMID- 17033122
TI - Isolated left lung aplasia with bronchial asthma.
AB - Congenital lung anomalies are categorised as pulmonary agenesis, aplasia and
hypoplasia with distinct clinical implications. An 8-year-old boy was referred
for an opaque left hemithorax for which he had received antituberculous therapy.
A detailed evaluation including flowing contrast computed tomography of the
thorax and fiberoptic bronchoscopy led to a diagnosis of left lung aplasia. He
also had wheezing dyspnea, which was confirmed as bronchial asthma. Congenital
lung defects with associated asthma was reported only twice till date. A high
index of suspicion is required to recognise such a patient.
PMID- 17033123
TI - Multiple familial trichoepitheliomas.
PMID- 17033124
TI - Management of traumatic hemobilia with embolization.
PMID- 17033125
TI - Non-albicans Candida in neonatal candidemia.
PMID- 17033126
TI - Intravenous breast milk administration--a rare accident.
PMID- 17033127
TI - Post concussion ataxia following minor head injury.
PMID- 17033128
TI - Procedural sedation and analgesia by non-anesthesiologists.
PMID- 17033130
TI - Role of experimental and epidemiological evidence of carcinogenicity in the
primary prevention of cancer.
AB - Experimental chemical carcinogenesis, which included long-term tests in
experimental animals,had a dominating role in cancer research between the 1920s
and the late 1960s. Two events marked a certain decline of confidence in the
ability of experimental results to predict human risks: the incapacity of
developing methods to identify agents acting on the different steps of the
carcinogenesis process, and the incapacity to reproduce experimentally the strong
evidence of carcinogenicity of tobacco smoke provided by epidemiological studies.
It was at that time that epidemiologists and biostatisticians developed criteria
for assessing the causation of chronic-degenerative diseases relying primarily on
epidemiological evidence. In 1969 the International Agency for Research on Cancer
(IARC) did initiate a programme for identifying the cause of cancer with the aim
of promoting the primary prevention of cancer. The programme is focused on the
evaluation of the carcinogenicity of environmental agents on the basis of both
the experimental and epidemiological evidence and, since the 1990s, a balanced
use of the new tools provided by advances in toxicology, molecular biology and
genetics. A strong point of the IARC programme is that in the absence of adequate
human data it is reasonable and prudent to regard agents for which there is
sufficient experimental evidence of carcinogenicity as if they were carcinogenic
to humans.
PMID- 17033131
TI - Structure-activity models of chemical carcinogens: state of the art, and new
directions.
AB - Chemical carcinogenicity has been the target of numerous attempts to create
predictive models alternative to the animal ones, ranging from short-term
biological assays (e.g. mutagenicity tests) to theoretical models. Among the
theoretical models, the application of the science of structure-activity
relationships (SAR) has earned special prominence. The qualitative approach to
SAR has lead to the identification of a large number of reactive chemical
substructures that are both mutagenic and carcinogenic. More sophisticated
developments are the quantitative structure-activity relationship (QSAR) models,
that link the physical chemical or structural properties of the molecules to the
toxicological endpoints. Both approaches provide strong support to the process of
risk assessment of the chemicals, especially in the phase of priority setting.
Among the areas potentially able to contribute to further developments of (Q)SAR,
the novel chemical relational databases are presented and discussed. The freely
downloadable ISSCAN database on chemical carcinogens is presented.
PMID- 17033132
TI - Towards a harmonized approach for risk assessment of genotoxic carcinogens in the
European Union.
AB - The EU Scientific Committees have considered in the past the use of matematical
models for human cancer risk estimation not adequately supported by the available
scientific knowledge. Therefore, the advice given to risk managers was to reduce
the exposure as far as possible, following the as low as reasonably achievable
(ALARA) principle. However, ALARA does not allow to set priorities for risk
management, as it does not take into consideration carcinogenic potency and level
of human exposure. For this reason the European Food Safety Authority (EFSA) has
identified as a priority task the development of a transparent, scientically
justifiable and harmonized approach for risk assessment of genotoxic carcinogens.
This approach, proposed at the end of 2005, is based on the definition of the
(MOE), i.e. the relationship between a given point of the dose reponse curve in
the animal and human exposure. As point of comparison EFSA recommends the BMDL10,
i.e. the lower limit of the confidence interval of the Benchmark Dose associated
with an incidence of 10% of induced tumors. Based on current scientific
knowkedge, EFSA concluded that a MOE of 10000 or greater is associated with a low
risk and low priority for risk management actions. The approach proposed does not
replace the ALARA. It should find application on food contaminants, process by
product, and other substances unintentionally present in food. On the other hand,
it is not intended to provide a tool for the definition of tolerable intake
levels for genotoxic carcinogens deliberately added to food.
PMID- 17033133
TI - Development of carcinogenicity classifications and evaluations: the case of
formaldehyde.
AB - In this paper carcinogenicity classification and evaluations case of formaldehyde
made by national and international agencies and organizations (such as European
Union, International Agency for Research on Cancer, World Health Organization)
both in occupational (such as American Conference of Government Industrial
Hygienists, National Institute of Occupational Safety and Health and Occupational
Health and Safety Administration) and non occupational environment (such as
United States Environmental Protection Agency) are proposed. The differences in
the database and consequently in the conclusion are described in a short
historical review since formaldehyde was considered for the first time as regard
as health effects.
PMID- 17033134
TI - Genotoxicity and carcinogenicity of acrylamide: a critical review.
AB - In 2002, public health concerns were raised by Swedish studies showing that
relatively high levels of acrylamide were formed during the frying, roasting, or
baking of a variety of foods, including potatoes, cereal products and coffee at
temperatures above 120 degrees C. Acrylamide possesses a range of hazardous
properties, the key effects being carcinogenicity, genotoxicity, neurotoxicity
and reproductive toxicity. Acrylamide is clearly carcinogenic in studies in
animals, in which it causes increased tumour incidence at a variety of sites.
Although the mechanisms for tumour induction in experimental animals have not yet
fully elucidated, the in vivo genotoxicity at gene and chromosome level in
somatic and germ cells in rodents cannot be discounted from contributing to it.
At this time, there is no information to indicate any significant difference
between rodents and humans in sensitivity to cancer formation from acrylamide.
The present available epidemiological studies of human industrial and accidental
exposures have to be considered not suitable for use in the cancer risk
assessment of acrylamide in food, due to several limitations. In reviewing the
genotoxicity and carcinogenicity of acrylamide, the author has taken into account
also the evaluations made by the IARC in 1994, the FAO/WHO in 2002 by the
European Commission Scientific Committee on Food (SCF) in 2002 and by the Joint
FAO/WHO Expert Committee on Food Additive (JECFA) in 2005.
PMID- 17033135
TI - Mortality study of employees in a factory of recovery and refining of catalytic
converters in Rome, Italy.
AB - The study objective is to describe cause specific mortality of employees in a
plant engaged in production, recovery and refining of catalytic converters
located in Rome. Previous epidemiological studies conducted in similar plants are
not available. A total of 828 workers (642 males and 186 females) were followed
up between 1956 and 31-12-2003. Cause specific standardized mortality ratio (SMR)
and 90% confidence intervals (CI) were computed using regional rates for
comparison. Among males hired between 1956 and 1993, followed up until
31/12/2003, mortality for all causes (SMR 0,8; 90% CI 0,7-1,0; 85 observed) and
all neoplasms (SMR 0,6; 90% CI 0,42-0,87; 20 observed) is below expected; an
increase is present for liver cirrhosis (SMR 2,74; 90% CI 1,47-5,1; 7 observed)
and brain cancer (SMR 5,24; 90% CI 2,3-11,90; 4 observed). The present
investigation complies with the proposed scientific standards for occupational
cohort studies. The study was not prompted by well defined a priori hypotheses
but it is included in a process intended to typify a potentially polluted site;
the absence of a priori hypotheses and of previous epidemiological evidence,
prevent from a causal interpretation of the increased mortality from liver
cirrhosis and brain cancer. The implementation of cohort studies in industrial
sites where industrial activities similar to the one here examined are present,
are highly recommended.
PMID- 17033136
TI - Molecular mechanisms of carcinogenesis by vinyl chloride.
AB - In 1974 vinyl chloride (VC), a gas used in the plastics industry, was shown to be
a human carcinogen, inducing a very rare type of tumor, angiosarcoma of the
liver. The same type of tumor was induced in rodents exposed to VC thus providing
an excellent model for mechanistic studies. Here, we review the numerous studies
on the mechanism of action of VC with particular emphasis on the DNA products
induced by this strong alkylating agent. In particular, the genotoxicity, repair
mechanisms, in vivo formation and tumor mutation spectra by etheno-adducts will
be analysed and possible approaches for future research suggested.
PMID- 17033137
TI - Tamoxifen (TAM): the dispute goes on.
AB - Tamoxifen (TAM) has been used since early '70s as antitumor agent in the adjuvant
therapy of breast carcinoma. The aim was (and is) to reduce the incidence of
contralateral breast cancer in primary breast cancer bearing patients. Its
efficacy was about 30% when estrogen and progesterone receptors were present in
the malignant breast tumor and its use in antitumor therapy is, at the present
time, rather correct. Viceversa, the employment of TAM in chemoprevention of
breast tumor in healthy and/or at-risk women by more than a decade has been
contrasting by many scientists and supporting by others. Indeed, TAM produces not
only beneficial effects but also detrimental effects (mainly induction of
endometrial cancer). According to the Author of this manuscript, TAM would not be
used for primary or secondary mammary tumor chemoprevention. For such purposes
the right way is to wait for conclusion of ongoing clinical trials on other pure
antiestrogenic agents. Indeed, good candidates to act as an antiestrogen both in
breast and in endometrial tissue are under validation. In the meanwhile, the
scientific dispute goes on.
PMID- 17033138
TI - Additional features of the worldwide double standards in the prevention of
asbestos-related diseases.
AB - A search has been made through Pubmed-Medline in order to quantify the production
of epidemiological studies on the consequences of asbestos in different
countries. Worldwide, very little epidemiological knowledge on the consequences
of occupational and environmental exposure to asbestos has been gathered in
countries known to be the major producers and/or consumers of asbestos. The only
exception is Canada, which ranks third among asbestos producers and exports most
of its production. A handful of papers carried out in Brazil are briefly
commented in order to highlight the difficulties that epidemiological
investigations face in developing countries.
PMID- 17033139
TI - Some non neoplastic effects of ELF magnetic fields in experimental animals.
AB - This study has been addressed to the non neoplastic effects observed in
experimental animals exposed to the ELF magnetic fields exposure, giving
particular attention to the large and comprehensive data of the two-year NTP
(National Toxicology Program) studies. The statistical analysis of non neoplastic
incidences, whenever not presented by the study authors, has been carried out in
the present study. Only the effects coherently emerging for both the animal
genders have been considered; gender specific effects have obviously been
separately analysed. The trend analysis has been carried out over the 4 exposure
levels (0, 2, 200 microT, and 1000 microT -microTesla) and on the first 3 ones.
For 28 dose-response relationships, non neoplastic effects significantly emerged
(6 for hyperplasia, 4 for cyst, 4 for inflammation, 3 for focus, 3 for atrophy, 2
for cellular infiltration, and 1 for each of other 6 effects). This number is
much higher than the one of neoplastic effects indicated by the NTP as
significant. For many of these dose-response relationships, the trend was
significant only over the first 3 treatment levels (excluding the highest one,
1000 microT/1 mT), in agreement with the results of some other studies indicating
a response reduction, or even a possible anticarcinogenic effects, at
considerably high exposures (mT range). The obtained results suggest a complex
effect modulation pattern.
PMID- 17033140
TI - Carcinogen-modified DNA and specific humoral immunity toward carcinogen-DNA
adducts. A review.
AB - Carcinogenesis is a complex and multistep process starting from initiation to
tumor progression. Damage to DNA, induced by the covalent binding of chemical
carcinogens on critical DNA segments, reflects exposure and is directly related
to tumor formation. For this reason it's very important detect and quantify DNA
adducts by using highly sensitive methods. During the last 30 years sophisticated
methods have been developed, in particular immunoassays that have a widespread
application in monitoring animal models and human tissues for evidence of
carcinogen exposure. In this paper we describe the work done in our laboratory,
from the production of antibodies specific for two different carcinogens, 2
Acetylaminofluorene and Benzo[a]pyrene, to their application in chemical
carcinogenesis studies. Moreover, we describe as immunological methods can be
used for detecting the presence of specific antibodies in sera of exposed
individuals.
PMID- 17033141
TI - [The HIV/AIDS epidemic in the Province of Sassari in the combination
antiretroviral therapy era].
AB - Combined antiretroviral therapy has reduced both AIDS mortality and morbidity. An
unknown proportion of patients is identified early and starts therapy before
developing AIDS, thus escaping epidemiological surveillance. For this reason it
is important to monitor the trend of new diagnoses of HIV infection. From the
comparison of patients living in the Province of Sassari with new diagnoses of
HIV infection or AIDS in the period 1997-2003 some differences emerge. Males are
the most affected, but the difference tends to decrease among new HIV cases.
Sexual contact is the most common route of transmission among new HIV diagnoses,
whereas the parenteral route prevails among AIDS cases. An increase in the
percentage of foreigners has been found only among new HIV cases. The difference
found between new AIDS and HIV cases emphasises the importance to implement HIV
infection based surveillance systems, in order to better guide informative
campaigns and other interventions.
PMID- 17033142
TI - [Molecular epidemiology of imported malaria in Italy: the use of genetic markers
and in vitro sensitivity test in a study of chloroquine resistance in Plasmodium
falciparum].
AB - The emergence of Plasmodium falciparum drug-resistance, especially chloroquine
resistance, represents one of the main obstacles to the control of malaria.
Several studies have shown that in P. falciparum the mechanism of chloroquine
resistance is linked to specific point mutations in the pfcrt gene of the
parasite. In the present study we have analyzed 120 Italian imported malaria
cases to evaluate the prevalence of 76T and 220S mutantions in the pfcrt gene.
Moreover, the correlation between the presence of pfcrt point mutations and in
vitro chloroquine resistance has been evaluated on 25 plasmodial isolates. The
results showed a high prevalence of the pfcrt point mutations in isolates
analyzed and a significant association between point mutations and in vitro
chloroquine resistance. Molecular screening on imported malaria cases can be a
useful tool to be employed in surveillance activity and also in monitoring the
development and spread of drug resistance in endemic areas.
PMID- 17033143
TI - [DNA-microarray: new technological approaches on twin studies].
AB - The completion of the Human Genome Project, and the innovations introduced in
biotechnology are changing how to study twins. Here, we summarize some molecular
studies performed on populations of discordant monozygotic twins (MZ) applying
microarrays. Microarrays are an orderly arrangement of high numbers of probes
(DNA, RNA or proteins), immobilized onto a matrix. The microarray approach allows
a global analysis of gene expression, and therefore might point out the molecular
mechanisms of MZ twins' discordance, such as epigenetic mechanisms. The
application of microarray to twin studies will help better define, through
bioinformatics, the role of genes and environment in the development of human
diseases, thus suggesting new diagnostic and therapeutic approaches.
PMID- 17033144
TI - Animal welfare and protection during transport: the current legislative framework
in European Union.
AB - The Protocol on the protection and welfare of animals annexed to the Amsterdam
Treaty (1997) establishing the European Community requires that in formulating
and implementing agriculture and transport policies, the Community and the Member
States shall pay full regard to the welfare requirements of animals. In the field
of animal welfare, transport has been, and still is today, cause of much
controversy. Council Directive 91/628/EEC, amended by Directive 95/29/EC,
constitutes the current Community legislative framework. In the light of
experience gained under Directive 91/628/EEC at harmonising Community legislation
on the transport of animals, and the difficulties encountered due to the diverse
transposition of that Directive at national level, it was more appropriate to set
out Community rules in this field in a regulation. In fact Council Regulations
(EC) no. 97/1255, no 98/411 and no. 2005/1 were adopted subsequently to provide
more detailed rules. This paper is aimed to review the current EU legislation
affecting the animal transport.
PMID- 17033145
TI - [ADHD and multimodal intervention].
AB - During the year 2003, the National Register of the Attention deficit
hyperactivity disorder (ADHD) has been implemented in Italy. It was commissioned
by the Ministry of Health to the Istituto Superiore di Sanita, which is its
leading technical and scientific body, with the aim to set up a sound database
gathering detailed information on the prescription of Ritalin at the national
level. The latter represents the most diffused elective drug treatment for such
an early-onset neuropsychiatric syndrome. To this aim, the more prevalent
theories on the pathogenesis of ADHD and the debate on therapy are reviewed and
discussed. This paper is aimed at emphasizing that this kind of systematic data
gathering of such a Register has not to be meant an unconditional approval of a
therapeutical approach based on drug therapy only. Pharmacological therapies may
or may not be included within the frame of a multimodal complex treatment plan
which should also rely on psychological intervention.
PMID- 17033146
TI - Evidence-based medicine for neurosurgeons: introduction and methodology.
AB - Evidence-based medicine is a tool of considerable value for medicine and
neurosurgery that provides a secure base for clinical practice and practice
improvement, but is not without inherent drawbacks, weaknesses and limitations.
EBM finds answers to only those questions open to its techniques, and the best
available evidence can be a far cry from scientific truth. With the support and
backing of governmental agencies, professional medical societies, the AAMC, the
ACGME, and the ABMS, EBM is likely here to stay. The fact that: (1) EBM
philosophy and critical appraisal techniques have become fully integrated into
the training and culture of our younger colleagues, (2) that maintenance of
certification will require individuals to demonstrate personal evidence based
practice based on tracking and critical analysis of personal practice outcomes as
part of the performance-based learning and improvement competency, and (3) that
the progressively growing national healthcare expenditures will necessitate
increasing basis of reimbursement and funding based on evidence-based
effectiveness and guidelines, all point to the likelihood that complete immersion
of neurosurgical practice in EBM is inevitable. This article thoroughly explores
the history of EBM in medicine in general and in neurosurgery in particular.
Emphasis is placed on identifying the legislative and regulatory motive forces at
work behind its promulgation and the role that organized medicine has taken to
facilitate and foster its acceptance and implementation. An accounting of
resources open to neurosurgeons, and a detailed description EBM clinical decision
making methodology is presented. Special emphasis is placed on outlining the
methodology as well as the limitations of meta-analyses, randomized clinic
trials, and clinical practice parameter guidelines. Commonly perceived
objections, as well as substantive problems and limitations of EBM assumptions,
tools, and approaches both for individual clinical practice and health policy
design and implementation are explored in detail.
PMID- 17033147
TI - Evaluation of epidemiologic evidence for primary adult brain tumor risk factors
using evidence-based medicine.
AB - We evaluate genetic, behavioral, developmental and experiential risk factors for
primary adult brain tumors (primarily, astrocytoma and meningioma) using a
systematic set of principles adapted from evidence-based medicine standards. In
addition to ionizing radiation, rare mutations in highly penetrant genes
associated with certain diseases/syndromes, and epilepsy and seizures (which
probably result from, rather than cause, adult brain tumors), only the
unexplained observation of familial aggregation of astrocytoma has been
consistently shown. There is promising renewed interest in associations between
infections, allergic conditions and adult brain tumor risk. Our knowledge of the
causes of adult brain tumors is limited and should be expanded by results from
large, well-designed studies of novel potential risk factors and potential
interactions between known and suspected risk factors.
PMID- 17033149
TI - Pediatric neurosurgery.
AB - Randomized controlled trials of neurosurgical procedures involving children have
been organized infrequently; as a consequence, the majority of pediatric
neurosurgical practice is not supported by class I data. Furthermore, many trials
that have been reported suffer from serious methodological shortcomings such as
insufficient power and poor statistical analysis. Finally, several trials of
neurosurgical techniques that are frequently performed on children have either
excluded children from participation or include an insufficient number of
children to draw strong conclusions. Despite these shortcomings, pediatric
neurosurgery, like all fields in medicine, is gradually moving towards a more
stringent evidence-based medicine standard. This chapter will attempt to
summarize the recent progress that has been made in this area.
PMID- 17033148
TI - Benign adult brain tumors: an evidence-based medicine review.
AB - BACKGROUND: Benign adult brain tumors can be managed conservatively or using
surgery, radiation, or medicines. While randomized comparisons assessing tumor
recurrence, quality of life, or survival are the ideal means of comparing
treatments, it can be difficult to recruit patients to such trials and lengthy
follow-up periods are needed because of the slowly progressive natural history of
these tumors. METHODS: Review of the literature on benign adult brain tumors
using evidence-based standards and focusing on meningiomas, pituitary adenomas,
and vestibular schwannomas, which together represent the majority of WHO grade 1
adult brain tumors. RESULTS: Nearly all studies of benign adult brain tumors were
of relatively poor quality (level 3 or poorer). These studies enable grade C
recommendations. The safety of meningioma surgery in the elderly varies with
institution, radiosurgery is a reliable alternative to surgery in small to medium
sized meningiomas, and the efficacy of drugs in therapy of meningiomas recurring
after surgery is difficult to interpret due to a lack of uniform criteria in the
studies. Radiosurgery is effective in nonfunctional pituitary adenomas recurring
after surgery, while phototherapy is a newer treatment modality with potential
benefits in pituitary adenomas that fail surgery or radiation. Vestibular
schwannomas can be conservatively managed, but there are no reliable predictors
of growth, so serial imaging is important. Radiosurgery has proven to be a
reliable alternative to surgery for small to medium-sized vestibular schwannomas,
but followup has been relatively short in most studies to date. CONCLUSIONS:
While randomized clinical trials comparing conservative management, surgery,
radiation, and medical management of benign adult benign tumors are unlikely to
occur, there is some level 3 evidence that can assist in their treatment.
PMID- 17033150
TI - Cerebrovascular-endovascular.
AB - This chapter will review the current status of scientific knowledge to support
evidence-based medicine guidelines for the endovascular treatment of
cerebrovascular disease. Three major areas of cerebrovascular disease will be
examined, (1) occlusive cerebrovascular disease, (2) vascular malformations and
(3) intracranial aneurysms. Levels of evidence vary in each area and the reasons
for this variation as well as the challenges that may limit further
investigations are discussed.
PMID- 17033151
TI - Evidence-based guidelines in lumbar spine surgery.
AB - Lumbar fusion is a commonly performed procedure for the treatment of painful
instability of the spine, usually manifest as chronic low back pain. The safety,
efficacy, and cost of these procedures have been questioned in the professional
and lay press. Recently, evidence based medicine techniques have been used to
investigate the role of lumbar fusion for the treatment of a variety of spinal
disorders. This chapter describes the general principles and procedures used for
the development of evidence based guidelines for the performance of lumbar
fusion.
PMID- 17033152
TI - Spine: minimally invasive techniques.
AB - Minimally invasive spine surgery decompression, arthrodesis, and instrumentation
techniques are now being applied in a wide variety of percutaneous, laparoscopic
and minimal access procedures. There is currently little longitudinal long-term
data on these procedures to document their efficacy, indications, limitations or
complications as compared to standard open techniques. Further complicating such
direct comparisons is that widely used spine outcomes instruments often do not
capture the relative benefits of these new procedures. It is only through
randomized trials that the potential benefits of these procedures be
substantiated in order to justify the sometimes significant increased costs
associated with them.
PMID- 17033153
TI - An evidence-based medicine review of stereotactic radiosurgery.
AB - BACKGROUND: Stereotactic radiosurgery has been increasingly utilized to manage a
wide variety of indications including vascular malformations, benign and
malignant tumors, and functional disorders. METHODS: Review of the recent
literature on stereotactic radiosurgery by evidence-based standards. RESULTS: The
vast majority of published papers on stereotactic radiosurgery is of rather poor
quality (level 3 or below). Two studies provide level 1 evidence showing an
improvement in local tumor control or survival for patients with 1-3 brain
metastases having radiosurgery in conjunction with whole brain radiation therapy
when compared to patients having whole brain radiation therapy alone. One
randomized trial found no improvement in facial pain outcomes for trigeminal
neuralgia patients having a longer segment of the nerve irradiated. CONCLUSION:
For a variety of reasons it is unlikely that randomized clinical trials will be
performed to evaluate the clinical usefulness of stereotactic radiosurgery.
Nonetheless, the preponderance of level 3 information supports the role of
radiosurgery as either an adjunct or alternative to surgical resection or
fractionated radiation therapy.
PMID- 17033154
TI - Evidenced-based guidelines for traumatic brain injuries.
AB - An enormous amount of clinical and basic science brain injury research has been
undertaken during the last several decades in an effort to improve outcomes
following severe traumatic brain injury, but to date there still are no new
therapies that have been clearly shown to be beneficial. There is, however,
increasing evidence to suggest that evidence-based, protocol-driven, acute care
can lead to improved outcomes. Evidence based guidelines for the medical and
surgical management of severe brain injury, and for penetrating and pediatric
brain injury, as well as for the pre-hospital management of brain injury, have
all been published. In this chapter the conclusions of those guidelines is
reviewed. In addition, the studies that demonstrate improved outcomes as a result
of implementation of the guidelines are summarized.
PMID- 17033155
TI - Treatment of chronic pain with neurostimulation.
AB - Chronic pain conditions are a complex and multifactorial problem generally
requiring a multidisciplinary-type approach. The central nervous system at some
point clearly becomes involved in the processing of these painful conditions with
an integration of complex changes in neurophysiology and behavior. Many ablative
techniques have been employed in the past to interrupt these signals. However,
the results were often temporary and symptoms tended to recur. The more modern
approach has suggested that modulation of the nervous elements may be a more
resilient approach for treating such chronic pain disorders. We are realizing
that many of these pain conditions are also dynamic and evolving, and as such
need a similar treatment modality. Neurostimulation, thus, provides the ability
of therapeutically dosing electrical current in a variety of pulse forms,
amplitudes, pulse widths, and frequencies, to affect that system. Furthermore, it
is not destructive, it is reversible, and it can be remotely adjusted and
programmed over time; clear advantages to previous surgical therapies. This
chapter reports on the current evidence for the use of neurostimulation (i.e.
spinal cord stimulation, motor cortex stimulation and deep brain stimulation) in
the treatment of chronic pain conditions.
PMID- 17033156
TI - Academic skills: I got my own laboratory! And now what?
PMID- 17033158
TI - Effects of p-nonylphenol and 4-tert-octylphenol on the anterior pituitary
functions in adult ovariectomized rats.
AB - p-Nonylphenol (NP) and 4-tert-octylphenol (OP) are known to mimic the action of
estrogens as endocrine disruptors. However, their acute effects on the pituitary
and the hypothalamus functions in vivo have been uncertain. We therefore
determined their effects on the anterior pituitary, in particular, gonadotropin
secretion. Two weeks after ovariectomy, the rats were given a subcutaneous
injection of 10 mg NP, 10 mg OP, 10 mg bisphenol A, 1 microg 17beta-estradiol, or
sesame oil alone as control. Twenty-four hours after the treatment, the
expression of progesterone receptor mRNA in the anterior pituitary and the level
of luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were
determined. The expression of progesterone receptor mRNA in the anterior
pituitary was significantly increased by either NP, OP, bisphenol A, or
estradiol, but bisphenol A was less effective. The level of LH was significantly
decreased by either NP or OP, but not by bisphenol A and estradiol. Only
estradiol significantly increased the level of prolactin. The level of follicle
stimulating hormone was unchanged by any of the treatments. To check the effects
of NP and OP on pulsatile LH secretion, blood samplings were done at 6-min
intervals for 3 h. Twenty-four hours after treatment in ovariectomized adult
rats, we found that the injection of NP significantly decreased the amplitude of
LH pulses and the mean LH concentrations, but not the frequency of LH pulses. The
injection of OP significantly decreased the mean LH concentrations without
affecting the frequency and amplitude of the LH pulses. Finally, the rats given
an injection of NP or sesame oil were intravenously injected with 50 ng of
gonadotropin-releasing hormone (GnRH) to check whether NP affected the LH
secretory responsiveness of the anterior pituitary to GnRH. We found that the
responsiveness to GnRH in NP-injected rats was significantly attenuated compared
to the sesame oil-injected rats. The present study suggests that NP, even with a
single injection, suppresses the pulsatile LH secretion in adult ovariectomized
rats, probably by affecting the anterior pituitary level.
PMID- 17033159
TI - Hearing in patients with intracanalicular vestibular schwannomas.
AB - This paper reports data on the spontaneous course of hearing in 156 patients with
purely intracanalicular vestibular schwannomas. The mean pure tone average (PTA)
was 51 dB HL and the mean speech discrimination score (SDS) 60% at diagnosis. The
risk of a significant subsequent hearing loss (>or=10 dB PTA or >or=10% SDS) was
54% during 4.6 years of observation. Patients with normal speech discrimination
at diagnosis had a significantly smaller risk of loosing hearing. The hearing
loss at diagnosis and during observation was not related to age, gender,
diagnostic tumor size, tumor- induced expansion of the internal auditory canal or
tumor sublocalization (fundus, central or porus). However, the loss of PTA was
smaller in shrinking tumors and the PTA deterioration rate correlated with the
volumetric tumor growth rate. After 4.6 years observation, the PTA had increased
by 14 dB to 65 dB HL, and the SDS reduced by 17% to 43%. The proportion of
patients eligible for hearing preservation treatment as determined by word
recognition score class I (70-100% SDS) was reduced to 28% (a 44% reduction), and
by AAO-HNS class A to 9% (a 53% reduction).
PMID- 17033160
TI - Effect of age and cognition on childhood speech in noise perception abilities.
AB - This research on children's speech in noise and cognitive abilities aimed to
determine the age-related trends in speech in noise perception abilities and the
relationship between speech in noise perception and cognitive abilities.
Monosyllabic distinguishable (consonant-vowel-consonant) words was the most
recognisable word category, followed by monosyllabic confusable words (consonant
vowel-consonant), disyllabic non-words (/aCa/) and monosyllabic syllables (/Ca/),
demonstrating that phoneme distinctiveness and a reduction in word confusability
contribute to their recognition. Older children outperformed younger children on
all speech in noise tasks, indicating that there are age-related trends in speech
in noise abilities. Children with higher cognitive abilities did not outperform
children with lower cognitive abilities on speech in noise tasks, indicating that
the ability to hear speech in noise may be an intrinsic feature of the auditory
system that matures with age.
PMID- 17033161
TI - Identification of novel mutations in the KCNQ4 gene of patients with nonsyndromic
deafness from Taiwan.
AB - Ion channels play important roles in signal transduction and in the regulation of
the ionic composition of intra- and extracellular fluids. Mutations in ion
channels have long been thought to be responsible for some forms of hearing loss.
Defects in KCNQ4, a voltage-gated potassium channel, are a cause of nonsyndromic
sensorineural deafness type 2, an autosomal dominant form of progressive hearing
loss. We present data of mutation analysis of KCNQ4 from 185 unrelated Taiwanese
probands with nonsyndromic hearing loss. The analysis revealed three novel KCNQ4
mutations and many polymorphisms. The prevalence of KCNQ4 gene mutations in this
study was 1.62% (3/185). The mutations include a missense mutation (F182L) and
two silent mutations (R216R and T501T). The F182L missense mutation was located
in the S3 domain of KCNQ4. The F182 residue of KCNQ4 is highly conserved in KCNQ4
among various species and is less conserved in all members of the KCNQ family. In
addition, although R216R is a silent mutation and does not alter the content of
amino acid residue, the neural network prediction system revealed that it can
potentially create a novel splice donor site during transcription. This mutation
might affect the protein structure of KCNQ4 and consequently the normal function
of the K+ channel. Our data provide the first comprehensive analysis of the KCNQ4
gene in Taiwanese patients with nonsyndromic deafness.
PMID- 17033162
TI - Auditory brainstem implantation to rehabilitate profound hearing loss with
totally ossified cochleae induced by pneumococcal meningitis.
AB - Hearing rehabilitation by cochlear implantation is not always possible in case of
total ossification after pneumococcal meningitis. We report 3 cases of
postmeningitis profound hearing loss with total cochlear ossification in adults
who underwent auditory brainstem implantation (Nucleus 22, Cochlear Inc., Lane
Cove, Australia) between 1999 and 2004. The postoperative follow-up period ranged
from 1 to 6 years. Eleven to 15 out of 22 electrodes were activated. All patients
had significant speech discrimination in the sound-only mode and an enhanced lip
reading performance with the implant. Auditory brainstem implants are an
efficient means of auditory rehabilitation and may be considered in selected
cases of bilateral profound hearing loss with the impossibility of cochlear
implantation.
PMID- 17033164
TI - It's time to distinguish the sign 'creeping eruption' from the syndrome
'cutaneous larva migrans'.
PMID- 17033163
TI - Audiological outcome of infants with congenital cytomegalovirus infection in a
prospective study.
AB - The aim of this study was to evaluate the audiological outcome of long-term
follow-up of infants with asymptomatic congenital cytomegalovirus (CMV) infection
as defined by the presence of CMV DNA in neonatal urine. 12599 pregnant women
underwent screening for CMV IgG and IgM antibodies between 1996 and 2003.
Eighteen infants with congenital CMV infection were identified. These infants
underwent the newborn hearing screening test or auditory brainstem response test.
Follow-up hearing assessments were performed with the auditory brainstem response
and behavioral audiometry. The seropositive rate of CMV IgG antibody among the
pregnant women was 75.3%, and the yearly seropositive rate decreased over the
study period. One hundred and forty-six pregnant women were positive for IgM
antibody, and 18 neonates (12.3%) had congenital CMV infection. Sensorineural
hearing loss (SNHL) was detected in 4 (25%) of the 16 infants with asymptomatic
infection and 1 (50%) of the 2 infants with symptomatic infection during the
first 6 months of life. Two infants who passed the newborn hearing screening had
a delayed-onset SNHL in follow-up examinations up to 4 years of age. Two had
progressive hearing loss and 2 had improvement of hearing loss. Screening of
pregnant women for CMV infection and repeated audiological examinations of
infants are necessary because there are infants with delayed-onset SNHL or
improved SNHL caused by asymptomatic congenital CMV infection.
PMID- 17033165
TI - Anti-tumor necrosis factor alpha-induced psoriasiform eruptions: three further
cases and current overview.
AB - The increasing use of anti-TNF-alpha agents led to a better knowledge of their
side effects. Among the cutaneous reactions, psoriasiform eruptions are
increasingly described. We encountered 3 further psoriasiform eruptions during
anti-TNF-alpha treatment for rheumatologic conditions and review the literature
in order to identify the common characteristics of these cases. We found 30 case
reports by using a comprehensive search of the 1966-2005 Medline database with a
wild variety concerning the psoriasis type of eruption, the anti-TNF-alpha agent,
the treatment duration and the presence or absence of a personal or familial
history of psoriasis. We conclude that a psoriasiform eruption during anti-TNF
alpha treatment seems to be a class effect, without any as yet known identified
predisposing factors, but it is more often self-limited and does not require
treatment discontinuation.
PMID- 17033166
TI - Detection of melanoma relapse: first comparative analysis on imaging techniques
versus S100 protein.
AB - BACKGROUND: Early detection of melanoma recurrence is essential for the patient's
prognosis. The serum S100 level may be a useful tool to detect relapse early.
OBJECTIVE: To compare the efficacy of imaging techniques and serum S100 in the
early detection of melanoma progression. This is the first report of a comparison
of a serum marker with an imaging tool in the follow-up of melanoma patients.
METHODS: From 1992 to 2003, we screened 192 patients suffering from melanoma
recurrence after a disease-free interval. Of those, 127 patients were identified
whose S100 levels had been assessed parallel to imaging procedures. RESULTS:
Serum S100 was elevated in 37% of patients at the time of relapse. In stage III,
32% of the patients had elevated S100 levels whereas in case of progression to
stage IV, 48% of the patients presented with increased S100. In 5.5% of patients,
S100 was the first indicator of disease progression. Imaging procedures lead to
detection of melanoma recurrence in 26.8%. CONCLUSION: A rising level of serum
S100 is a specific and sensitive marker of melanoma progression.
PMID- 17033167
TI - Aberrant DNA methylation silences the novel heat shock protein H11 in melanoma
but not benign melanocytic lesions.
AB - BACKGROUND: The heat shock protein H11 is silenced in melanoma cell lines, where
its forced expression by demethylation with Aza-C triggers apoptosis. OBJECTIVE:
To examine whether H11 is silenced by aberrant DNA methylation in melanoma as
compared to nevi and normal skin tissues. METHODS: Cell suspensions from benign
intradermal nevi, atypical nevi and malignant melanoma tissues were used in
reverse-transcriptase PCR and methylation-specific PCR. Paraffin-embedded tissues
were stained with H11 antibody. RESULTS: H11 is methylated in 60-75% of melanoma
and atypical nevi, but not in normal skin or most benign nevi. Methylation is
inversely correlated with H11 expression. CONCLUSION: The heat shock protein H11
is silenced by aberrant DNA methylation in melanoma, but not benign melanocytic
lesions or normal skin melanocytes. The data suggest that H11 is a promising
target for the molecular therapy of melanoma.
PMID- 17033168
TI - A new mutation of the double-stranded RNA-specific adenosine deaminase gene in a
family with dyschromatosis symmetrica hereditaria.
AB - BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary
genodermatosis characterized by a mixture of hyperpigmented and hypopigmented
macules localized on the back of the extremities and caused by mutations in the
double-stranded RNA-specific adenosine deaminase (DSRAD) gene. OBJECTIVE: To
identify gene mutations of DSRAD in patients with DSH. METHODS: A Chinese
pedigree of typical DSH was subjected to mutation detection in DSRAD. Direct
sequencing of all PCR products of the whole coding regions of DSRAD was performed
to identify the mutation. RESULTS: A missense mutation 2747G-->T in the DSRAD
gene was found in the affected members but not in the healthy individuals in this
family and in 50 unrelated controls. CONCLUSION: Our study found a novel missense
mutation in exon 9 of the DSRAD gene. We add new variants to the knowledge of
DSRAD mutations in DSH.
PMID- 17033169
TI - A review of malignancies observed during efalizumab (Raptiva) clinical trials for
plaque psoriasis.
AB - BACKGROUND: Psoriasis is a chronic, incurable immune-mediated disease. Most
therapies used for moderate to severe psoriasis are immunosuppressive. Agents
that depress immune function, including traditional psoriasis therapies, have
been associated with an increased incidence of malignancies. Efalizumab is a
recombinant monoclonal immunoglobulin G1 (IgG1) antibody approved for use in
psoriasis patients. OBJECTIVES: To evaluate the incidence of malignancy in
patients receiving efalizumab during clinical trials compared with placebo
treated patients, psoriasis patients from external cohorts and the general US
population. METHODS: Patient data were pooled from multiple phase III placebo
controlled, open-label efalizumab clinical trials, and the incidence rate of
reported malignancies was calculated as a function of patient years of
observation. The results for the efalizumab-treated patients were compared with
the data on psoriasis patients from insurance claims databases and a registry of
events in the general population. RESULTS: The efalizumab- and placebo-treated
patients had similar incidence rates of malignancy, including lymphoproliferative
disease, solid tumor, malignant melanoma and nonmelanoma skin cancer. The
incidence of nonmelanoma skin cancers, including basal cell carcinoma and
squamous cell carcinoma, in patients receiving efalizumab or placebo was elevated
relative to the external databases. CONCLUSIONS: These results suggest that
efalizumab treatment does not increase a patient's risk for malignancy. The
difference observed with nonmelanoma skin cancer may be due to biases introduced
by the clinical trial methodology. Additional patient observation is necessary to
ascertain whether a link exists between efalizumab therapy and nonmelanoma skin
cancer above that normally observed in psoriasis patients.
PMID- 17033170
TI - Tumescent suction curettage in the treatment of axillary hyperhidrosis:
experience in 63 patients.
AB - BACKGROUND: Axillary hyperhidrosis is a common and most distressing problem,
which can be addressed by a variety of treatment modalities. OBJECTIVE: To assess
the value of tumescent suction curettage in the treatment of axillary
hyperhidrosis. METHODS: 63 patients (39 female, 25 male; mean age 30.3 +/- 7.6
years) with axillary hyperhidrosis were enrolled in the study. All patients were
treated in an outpatient setting with tumescent suction curettage of the axillary
cavity, using two entry sites. The results were evaluated with the iodine-starch
test after 4 weeks and after 6 months. Two years after the procedure, patient
satisfaction was evaluated as 'satisfied', 'partially satisfied' or
'dissatisfied'. RESULTS: None of the patients had early postoperative
complications of infection or seroma. All patients had a marked reduction of
hyperhidrosis after 4 weeks, confirmed by the iodine-starch test. After 6 months,
15 patients had high sweat rates and asked for repeat surgery. Two years after
the procedure, 49 patients were satisfied, 11 patients were partially satisfied
and 3 patients were dissatisfied. CONCLUSION: Tumescent suction curettage is a
safe and effective treatment of axillary hyperhidrosis resulting in a high level
of patient satisfaction. Some patients will need repeat surgery. Suction
curettage, however, should not be used as the first line of treatment in axillary
hyperhidrosis.
PMID- 17033171
TI - Meta-analysis of 5% imiquimod and 0.5% podophyllotoxin in the treatment of
condylomata acuminata.
AB - BACKGROUND: Genital warts are a common sexually transmitted disease caused by
human papillomaviruses. Podophyllotoxin 0.5%, approved for patient self
administration, has been used most extensively in the treatment of genital warts.
Imiquimod, a novel immune response modifier capable of inducing interferon-alpha
and a variety of cytokines, has been examined as a potential treatment for
genital warts. But 0.5% podophyllotoxin and 5% imiquimod have not been compared
in any extensive and formal studies, although they are the common topical agents
for genital warts. OBJECTIVE: To evaluate the efficacy and safety of topical 5%
imiquimod and 0.5% podophyllotoxin in the treatment of genital warts. METHODS: We
searched Medline (1966 to June 2005), Embase (1974 to June 2005) and the Cochrane
Controlled Trials Register (issue 3, 2005). Randomized controlled trials of 5%
imiquimod or 0.5% podophyllotoxin in the treatment of genital warts were
collected. Two reviewers extracted the data and independently assessed the
quality of the included medical literature. Then, meta-analysis was conducted.
RESULTS: Twelve studies including 3 placebo-controlled trials of imiquimod and 9
placebo-controlled trials of podophyllotoxin were included. The clinical cure
rates of imiquimod and podophyllotoxin were 50.34 and 56.41%, respectively,
without statistically significant differences between the two (p > 0.05). A
combined analysis of the 3 studies on imiquimod showed a statistically
significant difference to the placebo group [pooled odds ratio (OR) 11.65, 95%
confidence interval (CI) 6.05-22.44], as did a combined analysis of the 9 studies
on podophyllotoxin (pooled OR 16.70, 95% CI 7.06-39.48). The most common adverse
events of imiquimod were erythema, erosion, excoriation, itching and burning;
those of podophyllotoxin were burning, pain, erosion, itching and inflammation.
CONCLUSION: Imiquimod and podophyllotoxin possess similar curative effects on
condylomata acuminata but podophyllotoxin has more serious adverse effects.
PMID- 17033172
TI - Evaluation of the antibacterial activity of a special silk textile in the
treatment of atopic dermatitis.
AB - BACKGROUND: Increased skin Staphylococcus aureus colonization is frequently found
in atopic patients. The reduction of local overinfection decreases skin
inflammation and improves the flares. OBJECTIVE: To evaluate the effectiveness of
the antimicrobial activity of a silk fabric (MICROAIR DermaSilk) coated with
alkoxysilane quaternary ammonium with durable antimicrobial properties (AEGIS AEM
5572/5) in children affected by atopic dermatitis (AD). METHODS: Sixteen
children, 12 affected by AD with symmetric eczematous lesions on the antecubital
areas and 4 without any cutaneous disease, used, for 7 days, tubular arm covers
made of this special silk fabric but only one of each pair was coated with AEGIS
AEM 5572/5. Microbiological examinations were done with standard cultural swabs
and by means of quantification of bacterial agents using agar plates at baseline,
after 1 h and after 7 days. RESULTS: After 7 days a significant improvement in
the mean value of the 'local SCORAD' index was observed in both the covered areas
compared to the values obtained at baseline. The reduction in the mean number of
colony forming units per square centimetre was similar in both areas.
CONCLUSIONS: Although this special silk fabric seems to be able to improve skin
lesions in AD, we were unable to demonstrate that such silk fabrics coated with
AEGIS AEM 5572/5 have an antibacterial activity in vivo, as shown in vitro.
PMID- 17033173
TI - Antimicrobial silk clothing in the treatment of atopic dermatitis proves
comparable to topical corticosteroid treatment.
AB - BACKGROUND: Atopic dermatitis (AD) is aggravated by mechanical irritation and
bacterial colonization. OBJECTIVE: This study compared the efficacy of an
antimicrobial silk fabric (DermaSilk) with that of a topical corticosteroid in
the treatment of AD. METHODS: Fifteen children were enrolled and wore a dress,
where the left side was made of DermaSilk and the right side was made of cotton.
The right arm and leg were treated daily with the corticosteroid mometasone for 7
days. The treatment efficacy was measured with a modified EASI (Eczema Area and
Severity Index) and with an assessment by the patients/parents and by a
physician. All patients were evaluated at baseline, as well as 7 and 21 days
after the initial examination. RESULTS: All parameters showed that, irrespective
of the treatment, there was a significant decrease of eczema after 7 days. No
significant difference between DermaSilk-treated and corticosteroid-treated skin
could be observed. CONCLUSION: DermaSilk showed potential to become an effective
treatment of AD.
PMID- 17033174
TI - A case of vulvar pyoderma gangrenosum associated with collagenous colitis.
AB - Pyoderma gangrenosum is a reactive inflammatory dermatosis which belongs to the
spectrum of neutrophilic dermatoses. Due to a lack of diagnostic criteria,
pyoderma gangrenosum is mainly a diagnosis of exclusion. It is rarely observed on
the perineum, and vulvar involvement is even less frequent. Collagenous colitis
is an idiopathic inflammatory colonic disease that is included in the microscopic
colitides. The colonic mucosa and the crypt architecture are preserved but
histologic alterations are found. We describe a case of collagenous colitis
associated with vulvar pyoderma gangrenosum that improved spectacularly with
cyclosporine 3 mg/kg/day and the twice-daily application of topical tacrolimus
0.1%.
PMID- 17033175
TI - Angioma serpiginosum arranged in a systematized segmental pattern suggesting
mosaicism.
AB - In a 15-year-old Taiwanese girl, multiple purple punctate lesions arranged in a
systematized, segmental pattern had developed since childhood, beginning from the
right thigh and gradually progressing upwards to the right buttock, the left side
of the abdomen, circumventing to the left side of the back, and extending to the
right arm as well as to the posterolateral aspect of the left leg.
Histopathological examination showed dilated capillaries in the uppermost part of
the dermal papillae characteristic of angioma serpiginosum. The systematized,
segmental and asymmetric arrangement of lesions as noted in the present case
suggest that angioma serpiginosum reflects genetic mosaicism.
PMID- 17033176
TI - Aggressive CD30 large cell lymphoma after cyclosporine given for putative atopic
dermatitis.
AB - Atopic dermatitis (AD) is not regarded as a predisposing condition for cutaneous
T cell lymphoma. Cyclosporine (CsA) is an efficient therapy in AD, and its side
effects, including lymphocytic proliferation, are rare at the low dose used in
such cases. So far 3 cases of patients who developed cutaneous T cell lymphoma
under CsA treatment for atopy have been described. An adult patient with a
history of AD received CsA therapy because of an atypical flare-up of his
eruption. He rapidly developed papular atypical lesions, then followed by the
onset of a voluminous cutaneous tumor leading to the diagnosis of mycosis
fungoides (MF) transformed in CD30+ large cell lymphoma with nodal and blood
involvement. No improvement occurred after withdrawing of CsA, and he required a
polychemotherapy and an allograft. This case illustrates the dramatic evolution
of an MF under CsA given in the hypothesis of AD. It stresses the fact that skin
biopsies should be taken in case of atypical AD to rule out MF and avoid such an
aggressive evolution under immunosuppressive therapy.
PMID- 17033177
TI - Creeping hair: an isolated hair burrowing in the uppermost dermis resembling
larva migrans.
AB - A 55-year-old Japanese male presented with a slowly moving linear erythema that
looked like an eruption of creeping disease, or cutaneous larva migrans. The
eruption extended linearly along Langer's line of the lateral side of the abdomen
to the lower back, leaving wave-like erythema. In the top third of the
erythematous eruption, close examination demonstrated a black thin line, which
was revealed to be a hair shaft by a shallow incision of the skin. After removal
of the hair, the eruption diminished immediately, leaving a slight pigmentation.
An ingrown pubic hair seemed to have migrated with the lower end forward along
Langer's line, because of the arrangement of hair cuticle and the force of body
motion. Linearly moving erythematous eruptions that look like that of larva
migrans should be differentiated from creeping hair by close examination
detecting burrowing hair.
PMID- 17033178
TI - Pseudonits in dreadlocked hair: a louse-y case of nits.
AB - We report a case of pseudonits in dreadlocked hair, with prominent hair roots of
shed hair closely resembling Pediculosis humanus capitis infestation.
PMID- 17033179
TI - Multiple myeloma associated with porphyria cutanea tarda: a possible role of
bortezomib?
PMID- 17033180
TI - Generalized interstitial granuloma annulare induced by pegylated interferon
alpha.
PMID- 17033181
TI - Koebner phenomenon in dermatomyositis.
PMID- 17033182
TI - Regressive lichenoid eruption during an acute episode of Q fever.
PMID- 17033183
TI - Unilateral accentuation of X-linked ichthyosis following thoracotomy for lung
cancer.
PMID- 17033184
TI - Verruca vulgaris following treatment with tacrolimus ointment.
PMID- 17033185
TI - Angioma serpiginosum with extensive lesions associated with retinal vein
occlusion.
PMID- 17033187
TI - Human sebaceous glands: how studies of skin surface lipids have provided
knowledge of their function and control.
PMID- 17033188
TI - Aging of human sebocytes in vitro induced by exposure to a defined hormone
environment.
PMID- 17033189
TI - Potent corticosteroids inhibit lipogenesis in sebaceous glands.
PMID- 17033190
TI - Differential regulation of Toll-like receptor and CD14 pathways by retinoids and
corticosteroids in human sebocytes.
PMID- 17033191
TI - TLR2 and TLR4 polymorphisms are not associated with acne vulgaris.
PMID- 17033192
TI - Psoriasin and follicular hyperkeratinization in acne comedones.
PMID- 17033193
TI - Morphological changes in the rat sublingual gland parenchyma with aging.
AB - BACKGROUND: The characteristics of mucous cells in the aging rat sublingual gland
were investigated in this study. Particular attention was paid to accumulated
amyloid protein and changes of the properties of the secretory granules at the
histochemical and ultrastructural level. OBJECTIVE: This study was designed to
examine age-related morphological changes in the sublingual gland of male Wistar
rats from 12 to 27 months. METHODS: For light microscopy, the sublingual glands
were fixed with 10% neutral-buffered formalin, embedded in paraffin, and
processed for Alcian blue, Congo red, and TUNEL staining. For transmission
electron microscopy, some of the samples were fixed with Karnovsky solution,
postfixed with 2% osmium tetroxide, and embedded in epoxy resin for pronase
treatment. RESULTS: The sublingual gland showed slight shrinkage after 21 months.
After 24 months, Congo red staining showed positive reaction to the intralobular
connective tissue surrounding the terminal portions and to the interlobular
connective tissue around the blood vessels and the excretory ducts. At 27 months,
some of the granules in the serous demilunes had difficulty in digesting with
pronase treatment. The appearance rate of TUNEL-positive cells was low in both
mucous and serous portions during the observation period, though the positive
cell number was higher in the serous than in the mucous portion. CONCLUSIONS:
These findings indicate that the rat sublingual gland accumulates amyloid protein
in the parenchyma and changes the properties of secretory granules of the acinar
cells in the serous demilune with aging, though apoptosis of the parenchymal
cells and the decrease of the gland weight are slight.
PMID- 17033194
TI - Highlights in cellular and molecular mechanisms of allergic diseases. XXVth
Congress of the European Academy of Allergology and Clinical Immunology in
Vienna.
AB - This year, the annual congress of the European Academy of Allergology and
Clinical Immunology was held on 10-14 June in Vienna. More than 6,000 delegates,
practicing bench or bedside work or both, gathered from over 50 countries
throughout the world. Health professionals, basic scientists and fellows in
training could choose between a variety of activities in plenary, main,
educational and workshop sessions, highlights of the past year, pros and cons,
and oral abstract and poster sessions, and met with experts. A total of 1,713
abstracts, 31 symposia, and 54 workshops were presented, ranging from basic
science to clinical trials and modern treatment of allergic diseases. Here, we
summarize the highlights of cellular and molecular mechanisms of allergic
disease.
PMID- 17033195
TI - The role of protein glycosylation in allergy.
AB - The asparagine-linked carbohydrate moieties of plant and insect glycoproteins are
the most abundant environmental immune determinants. They are the structural
basis of what is known as cross-reactive carbohydrate determinants (CCDs).
Despite some structural variation, the two main motifs are the xylose and the
core-3-linked fucose, which form the essential part of two independent epitopes.
Plants contain both epitopes, insect glycoproteins only fucose. These epitopes
and other fucosylated determinants are also found in helminth parasites where
they exert remarkable immunomodulatory effects. About 20% or more of allergic
patients generate specific anti-glycan IgE, which is often accompanied by IgG.
Even though antibody-binding glycoproteins are widespread in pollens, foods and
insect venoms, CCDs do not appear to cause clinical symptoms in most, if not all
patients. When IgE binding is solely due to CCDs, a glycoprotein allergen thus
can be rated as clinical irrelevant allergen. Low binding affinity between IgE
and plant N-glycans now drops out as a plausible explanation for the benign
nature of CCDs. This rather may result from blocking antibodies induced by an
incidental 'immune therapy' ('glyco-specific immune therapy') exerted by everyday
contact with plant materials, e.g. fruits or vegetables. The need to detect and
suppress anti-CCD IgE without interference from peptide epitopes can be best met
by artificial glycoprotein allergens. Hydroxyproline-linked arabinose (single
beta-arabinofuranosyl residues) has been identified as a new IgE-binding
carbohydrate epitope in the major mugwort allergen. However, currently the
occurrence of this O-glycan determinant appears to be rather restricted.
PMID- 17033196
TI - Tensile residual strains on the elastic lamellae along the porcine thoracic
aorta.
AB - AIMS: This study determines the residual strains on the elastic lamellae in the
porcine thoracic aorta to understand the distribution of strains amongst the
components of the vascular wall. METHODS: Residual strains in aortic rings were
released by cutting and purifying the elastin. Strains were calculated from
lamellar contour lengths based on lamellar waviness and from mechanical tests.
RESULTS: On the release of residual strains, waviness decreased 2-7%, the inner
lamellae shortened 2.1 +/- 0.6% and the outer lamellae shortened 7.1 +/- 0.4% (p
< 0.001), indicating that all lamellar elastin was under tension in fresh aortic
tissue. Lamellar shortening was 3% greater in the distal than in the proximal
tissue. Mechanical tests confirmed the morphological results and showed that the
residual strains in fresh tissue required both the elastic tissue and the
vascular smooth muscle. Tensile residual strains averaging 1.0% remained in the
uncut elastin rings. CONCLUSION: When waviness is considered, the residual
strains on the individual wall components can differ from the surface residual
strains based only on the ring perimeter. The residual strains on the inner
elastic lamellae are tensile, not compressive. The strain distribution amongst
the individual components is non-uniform and not adequately understood to
determine the physiological strains in the aortic wall.
PMID- 17033197
TI - Gestational stress leads to depressive-like behavioural and immunological changes
in the rat.
AB - Stress during pregnancy, gestational stress, can increase the chance of
developing postpartum depression, which is estimated to occur in 10% of women.
Since major depression is accompanied by an activation of the inflammatory
response system, the aim of this study was to investigate if stress during
pregnancy induces postpartum depressive-like behaviour, and if so, is it
accompanied by activation of the inflammatory response system in female Fisher
rats. We investigated the effect of gestational stress on the production of
depressive-like behaviour in the rats. The pregnant dams underwent daily
restraint stress (for 1 week, 3 times/day) or were left undisturbed (control). On
postpartum day 22, the rats were introduced to the forced swim test (pre-test).
On postpartum days 23 and 24 (test days), the immobility time was measured.
Gestational stress significantly elevated immobility scores by 35-40% above the
control values on both test days, which suggests that the stressed group
displayed postpartum depressive-like behaviour. The concentrations of the pro
inflammatory cytokines interleukin-1beta, tumour necrosis factor-alpha and the
anti-inflammatory cytokine interleukin-10 in stimulated whole-blood culture were
also analysed. The stressed group showed higher levels of all three cytokines. No
significant differences in the cytokine concentrations were detected in the
hypothalamus, hippocampus or pre-frontal cortex.
PMID- 17033198
TI - Intrathecal immunoglobulin G synthesis and brain injury by quantitative MRI in
multiple sclerosis.
AB - OBJECTIVES: It was the aim of this study to evaluate if the quantitative
intrathecal immunoglobulin G (IgG) synthesis correlates with the brain atrophy
and the total lesion volume (TLV) in brain magnetic resonance imaging (MRI) of
multiple sclerosis (MS) patients. METHODS: A total of 50 patients with relapsing
remitting MS were included in this study. MRIs were performed and cerebrospinal
fluid samples were collected during the diagnostic determination when patients
were in remission without treatment. RESULTS: At study baseline, IgG index values
were elevated in 36 patients (72%), and oligoclonal IgG bands were positive in 42
of 50 patients (84%). Brain MRI was abnormal in 94% of patients, and, compared
with healthy controls, brain atrophy was observed in MS patients. A positive
correlation among IgG index, cerebrospinal fluid leukocyte count and TLV was
observed; the Expanded Disability Status Scale correlated positively with TLV and
the number of lesions, although a significant relationship between disability and
brain atrophy was not demonstrated. CONCLUSIONS: Although new parameters will be
necessary in longitudinal studies to characterize the axonal injury in various
stages of the disease, the data suggest that the high intrathecal IgG synthesis
may predict a greater brain lesion burden.
PMID- 17033199
TI - DNA aptamers that bind to MUC1 tumour marker: design and characterization of MUC1
binding single-stranded DNA aptamers.
AB - Agents able to bind tightly and selectively to disease markers can greatly
benefit disease diagnosis and therapy. Aptamers are functional molecules, usually
DNA or RNA oligonucleotides, with the appropriate sequence and structure to form
a complex with a target molecule. MUC1 is a well-known tumour marker present in a
variety of malignant tumours and it has been a target of interest for many years.
In this work we report the selection of DNA aptamers that bind with high affinity
and selectivity to the MUC1 peptides. Combinatorial chemistry techniques based on
the SELEX methodology were used for the identification of the specific aptamers.
These were selected from an initial library containing a 25-base-long variable
region, resulting in 4(25) random sequences of single-stranded DNA molecules, for
their ability to bind to synthetic forms of MUC1. Ten rounds of in vitro
selection were performed enriching for MUC1 binding. By round ten more than 90%
of the pool of sequences consisted of MUC1-binding molecules. Selected aptamer
families were cloned, sequenced and found to be unique, sharing no sequence
consensus. The binding properties of these aptamers were quantitated by enzyme
linked immunosorbent assay and surface plasmon resonance, whereas their
specificity for MUC1-expressing cancer cells has been validated using fluorescent
microscopy. Aptamers offer significant advantages over existing antibody-based
recognition procedures in that they offer higher binding affinity (higher
retention/reduced dissociation) and specificity to the target (ability to
determine variations on the protein target down to single amino acid changes),
higher selectivity against mutated protein epitopes and potentially reduced
immunogenicity and increased tumour penetration associated with their size.
PMID- 17033200
TI - Multidrug resistance in locally advanced breast cancer.
AB - BACKGROUND: Advanced breast cancer cases can still be encountered resulting in
poor prognosis. The primary treatment for these patients is chemotherapy, and
multidrug resistance (MDR) is a serious obstacle in the treatment. Detecting drug
resistance before first-line chemotherapy may increase the patient's survival. In
this study, the role of MDR is evaluated in locally advanced breast cancer
patients. METHODS: Reverse transcriptase polymerase chain reaction was used for
the detection of MDR genes, ABCB1 and ABCC1. Immunohistochemistry was used for
the detection of MDR proteins, P-glycoprotein (Pgp) and MDR-associated protein 1.
RESULTS: Breast tissues from 25 patients both before and after chemotherapy were
examined. Five patients were unresponsive to chemotherapy. Four had ABCB1 gene
expression induced by chemotherapy, and Pgp positivity was detected in 9 patients
after chemotherapy. Both the induction of ABCB1 gene expression (p < 0.001) and
Pgp positivity (p < 0.001) during chemotherapy were significantly related with
clinical response. Although 80% of the clinically unresponsive patients had ABCC1
gene expression, the relation between ABCC1 expression and clinical drug response
was not significant. CONCLUSION: In locally advanced breast cancer, ABCB1 gene
expression during chemotherapy contributes to clinical unresponsiveness. However,
ABCC1 gene expression did not correlate strongly with the clinical response.
PMID- 17033201
TI - Evaluation of an improved tissue inhibitor of metalloproteinase 1 dual monoclonal
sandwich immunoassay.
AB - BACKGROUND: It has previously been shown that increased levels of plasma tissue
inhibitor of metalloproteinase 1 (TIMP-1) is associated with shorter survival for
patients with colorectal cancer (CRC). Furthermore, plasma TIMP-1 levels have
been found to be elevated in patients with early-stage CRC. OBJECTIVE: It was the
aim of this study to develop a new dual monoclonal antibody (mAb) sandwich
immunoassay for TIMP-1 in order to achieve better resolution of non-cancer and
cancer plasma specimens. METHODS: Chemiluminescence immunoassay techniques were
used to screen 240 combinations of TIMP-1 mAbs for their ability to interact with
each other and to allow for further characterization of the sandwiching antibody
pairs. Five mAb pair combinations were selected for assessment of their ability
to resolve non-cancerous and cancerous plasma specimens by TIMP-1 measurement.
Based on this testing, a final assay format was chosen for further validation.
The results for the final assay were compared with measurements obtained in a
TIMP-1 ELISA that had previously demonstrated the ability to resolve healthy
blood donors and CRC specimens. RESULTS: The clinical results support that the
new dual monoclonal immunoassay has statistical discrimination equivalent to the
ELISA. Additionally, the immunoassay had a high reproducibility and specificity.
CONCLUSION: The clinical evaluation of five TIMP-1 immunoassays resulted in the
development of a new immunoassay. The new TIMP-1 immunoassay showed superior
analytical performance to our previously used ELISA.
PMID- 17033202
TI - ALDH2 1510 G/A (Glu487Lys) polymorphism interaction with age in head and neck
squamous cell carcinoma.
AB - Recent molecular epidemiological studies have revealed a possible association of
the acetaldehyde dehydrogenase-2 (ALDH2) 1510 G/A (Glu487Lys) polymorphism with
various cancers including head and neck squamous cell carcinoma (HNSCC). To
further elucidate the significance of this polymorphism in HNSCC development, the
relationship between ALDH2 1510 G/A and clinicopathological parameters, cigarette
smoking or alcohol intake was evaluated in patients with HNSCC. DNA samples from
192 patients with primary HNSCC and 192 age- and gender-matched healthy controls
were genotyped and statistically evaluated. Although there was no significant
difference in the genotype distribution of ALDH2 1510 G/A between cases and
controls, we found that the frequency of the ALDH2 genotypes with the mutated A
(Lys) allele was greater in patients aged <66 years than in those aged > or = 66
years (p = 0.034). This tendency became more evident in patients with the habit
of drinking (n = 143; p = 0.009). The association of ALDH2 1510 G/A with age
remained significant after multivariate logistic regression analysis was
performed for the patients (odds ratio for an age interval for 1 year, 0.970; 95%
confidence interval, 0.943-0.998). The present data suggest a possible
interaction between the ALDH2 1510 G/A polymorphism and age in HNSCC.
PMID- 17033203
TI - Classical Hodgkin's lymphoma: molecular evidence for specific alterations in
circulating T lymphocytes.
AB - OBJECTIVE: Impairment in cell-mediated immunity has long been recognized in
classical Hodgkin's lymphoma (cHL). The immunosuppressive environment at the
tumor site and/or a primary T-cell defect may contribute to an ineffective immune
clearance of Hodgkin/Reed-Sternberg (H/R-S) cells. Here, we analyzed whether
circulating T lymphocytes of cHL patients show specific alterations in gene
expression with possible impact on anti-tumor immunity. MATERIAL AND METHODS:
Gene expression profiles were performed from CD3+ T cells isolated from
peripheral blood samples of untreated patients with cHL versus two control groups
consisting of healthy donors and patients with sarcoidosis. The regulation of
gene expression was confirmed in additional patients for selected genes by real
time RT-PCR. RESULTS AND CONCLUSION: Circulating T cells of cHL show a Th1 immune
response likely supporting anti-tumor immunity. However, the molecular profile
reveals an association between cell cycle transition/proliferation and induction
of immune regulatory genes which may limit an effective anti-tumor immune
response of differentiated Th1 cells.
PMID- 17033204
TI - Treatment of locally advanced prostate cancer--the case for radical
prostatectomy.
AB - The treatment of clinically locally advanced prostate carcinoma (stage cT3)
remains controversial. One of the main reasons for this controversy results from
the substantial staging error attached to the clinical diagnosis cT3 with
overstaged T2 tumors and understaged node-positive cases. Treatment options in
this situation include radical prostatectomy, external beam radiotherapy,
immediate or delayed androgen deprivation treatment and the so-called 'watchful
waiting'. Acceptable and often surprisingly good tumor-specific survival rates
have been reported for radical prostatectomy in pT3 series--based on good
clinical case selection--approaching those of pT2 series. In lymph node-positive
pT3 cases, adjuvant hormone deprivation seems to prolong survival which it does
not in lymph node-negative pT3 disease. A benefit of adjuvant external beam
radiotherapy after radical prostatectomy for pT3 cases in prolonging overall
survival has not been shown, despite the fact that it can prevent or delay
biochemical and local recurrence. External beam radiotherapy as the only
treatment for cT3 disease results in unfavorable tumor-specific survival rates,
which can be significantly improved with adjuvant hormonal treatment with LHRH
agonists. If, in case of advanced age and/or significant comorbidity, primary
hormonal treatment is chosen, early hormonal deprivation therapy seems to offer
marginal benefits in survival compared to delayed treatment.
PMID- 17033205
TI - Clinicopathological features of patients with biochemical recurrence after
radical prostatectomy without progressive rise in serum prostate-specific
antigen.
AB - INTRODUCTION: The objective of this study was to characterize clinicopathological
features of patients with biochemical recurrence after radical prostatectomy who
did not exhibit a progressive rise in serum prostate-specific antigen (PSA)
during the follow-up period. MATERIALS AND METHODS: We analyzed data from 162
consecutive patients who underwent radical prostatectomy for clinically organ
confined prostate cancer without neoadjuvant hormonal therapy and were followed
postoperatively for at least 1 year. The serum PSA value was measured using an
ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and
biochemical recurrence was defined as a serum PSA of >or=0.1 ng/ml. RESULTS: A
total of 32 patients (19.8%) were diagnosed as having biochemical recurrence.
Among these patients, we identified 10 (31.3%) with a serum PSA>0.1 ng/ml who had
not shown PSA or clinical progression during a median follow-up of 34 months
after radical prostatectomy. In these 10 patients, the median time to biochemical
recurrence was 17 months, the median PSA velocity after biochemical recurrence
was 0.034 ng/ml/year, and there was no patient whose serum PSA value became >0.4
ng/ml. There were no clinicopathological parameters except for PSA velocity that
were significantly associated with the features of these 10 patients. CONCLUSION:
Because of the presence of a subset of patients with biochemical recurrence after
radical prostatectomy who will not show a progressive increase in serum PSA
value, the indication for adjuvant therapy for such patients should be cautiously
determined considering several factors, such as PSA kinetics.
PMID- 17033206
TI - Variables which might predict the response to salvage radiotherapy in chinese
patients with biochemical failure after radical prostatectomy.
AB - BACKGROUND/AIMS: To evaluate the relationship between the variables and the
outcomes of salvage radiotherapy (sRT) to find some predictors of sRT. METHODS:
The medical records of 56 patients receiving sRT for biochemical failure after
radical prostatectomy (RP) were available for retrospective review. sRT was
defined as external beam radiotherapy for patients with a continuous increase in
the prostate-specific antigen (PSA) level of >or=0.2 ng/ml after RP. Response was
defined as achievement of a PSA nadir of 6 months were all responders. The response rate in
patients with seminal vesicle invasion was 42.9% (6/14) versus 76.2% (32/42) in
patients without seminal vesicle invasion (OR=0.119, p=0.015). CONCLUSION: PSADT
and the state of seminal vesicle invasion were good predictors of response to
sRT. sRT was especially effective when the PSADT was >6 months and in patients
without seminal vesicle invasion.
PMID- 17033207
TI - The use of erythropoietin in patients undergoing radical prostatectomy: effects
on hematocrit, transfusion rates and quality of life.
AB - OBJECTIVE: It was the aim of this study to prospectively study the effects on
hematocrit levels, transfusion rates and quality of life (QOL) indices in men
preoperatively supplemented with recombinant erythropoietin (rEPO) undergoing
radical prostatectomy for clinically localized prostate cancer. METHODS: Thirty
men undergoing radical prostatectomy were randomized either to receive rEPO
(n=25) or to serve as controls (n=25). Outcome measurements obtained
preoperatively, as well as 10 days and 6 weeks postoperatively included serum
hematocrit levels, transfusion rates and QOL indices (using SF-12 validated
questionnaires). RESULTS: The rEPO group had a significant increase in
preoperative hematocrit (median increase=4 points; p=0.002). Although there were
no significant differences in hematocrit at 10 days, the rEPO had a significantly
higher hematocrit value at 6 weeks (p=0.0086). No differences were observed in
transfusions rates between groups (4% in each group). SF-12 mental and SF-12
physical scores were not different between the two groups at any time point.
CONCLUSION: Preoperative administration of rEPO significantly increases
preoperative and postoperative hematocrit levels. However, no differences were
observed with regard to transfusion rates or postoperative QOL indices despite
these higher hematocrit values.
PMID- 17033208
TI - Laparoscopic radical prostatectomy in patients following transurethral resection
of the prostate.
AB - OBJECTIVES: Previous transurethral resection of the prostate (TURP) was reported
to impose difficulties during open radical prostatectomy. We describe our
experience in laparoscopic radical prostatectomy (LRP) following transurethral
resection of the prostate. PATIENTS AND METHODS: The series included 35 patients:
22 patients underwent transperitoneal LRP (tpLRP) and 13 underwent
extraperitoneal LRP (epLRP). The minimal interval between TURP and laparoscopy
was 3 months. Patients' charts were reviewed for their preoperative
characteristics, intraoperative difficulties and complications, and outcome.
RESULTS: Patients' mean age was 67.5+/-4.4 years. 12 patients were cT1a,b and 23
patients were cT1c/T2. Twenty-two patients underwent tpLRP and 13 underwent
epLRP. No statistical difference was found between the preoperative
characteristics and the pathological results of cT1a,b vs. T1c/cT2 patients, or
tpLRP vs. epLRP patients. Thirty-three procedures were completed laparoscopically
and 2 were converted to open surgery. Perioperative complications included two
leaking anastomoses, prolonged lymph drainage in 1 case, atelectasis (n=1) and
duodenal ulcer (n=1). Twelve positive margins were noted, half of them in pT2
tumors. The mean follow-up was 28.5 months. Twenty-five of 35 patients had more
than 12 months of follow-up. Among them 19 patients were completely continent
(76%) and 6 (24%), reported mild stress incontinence. CONCLUSIONS: Although LRP
following TURP is sometimes more technically difficult, simple modifications in
the operative strategy help facilitate surgery. LRP following TURP favorably
compares to open radical prostatectomy after TURP and laparoscopy in non-TURP
patients.
PMID- 17033209
TI - How far is the preoperative Kattan nomogram applicable for the prediction of
recurrence after prostatectomy in patients presenting with PSA levels of more
than 20 ng/ml? A validation study.
AB - OBJECTIVE: We present an external validation study investigating the
applicability of the preoperative Kattan nomogram for predicting recurrence after
prostatectomy in a population of patients with serum prostate-specific antigen
(PSA) levels exceeding 20 ng/ml. MATERIALS: In the evaluation of clinical
parameters pooled from a total of 191 patients presenting with PSA levels ranging
between 20.1 and 100 ng/ml, the PSA-free survival rate 60 months after surgery
was calculated according to Kattan nomograms. Subsequently, the results were
statistically compared with the corresponding actual survival rates obtained from
Kaplan-Meier analysis. For this purpose, the patients were assigned to one of
four different risk groups according to predictions derived from the Kattan
nomograms, enabling a direct comparison of expected (as predicted by Kattan
nomogram) versus actual survival of each patient investigated in our study.
RESULTS: Predicted PSA-free survival rates were determined to be as follows: 83%
(low risk group); 66% (intermediate risk group); 39% (intermediate-high risk
group), and 10% (high risk group) in comparison with the actual survival rates
determined to be 63, 62, 40 and 21%, respectively. For PSA levels ranging between
20.1 and 30 ng/ml, 30.1 and 50 ng/ml, and 50.1 and 100 ng/dl, PSA-free survival
rates were found to be 57, 37, and 27% (p=0.0017), respectively, during a 5-year
post-prostatectomy follow-up. CONCLUSIONS: The Kattan nomogram shows good
statistical concordance with actual survival rates in the mean risk quadrants,
but considerable differences were demonstrated concerning individuals with either
a high or with a low risk of cancer progression.
PMID- 17033210
TI - Validity and reliability of the arabic version of the National Institutes of
Health Chronic Prostatitis Symptom Index.
AB - INTRODUCTION: In order to accurately assess the extent of chronic pelvic pain
syndrome (CPPS) and to objectively measure symptoms for natural history studies
and to assess the outcome parameters for clinical trials, the National Institutes
of Health (NIH) Chronic Prostatitis Collaborative Research Network developed and
validated the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). The aim of the
current study was to develop and validate a fluent and comprehensive Arabic
version of the NIH-CPSI. METHODS: This study consisted of 80 consecutive male
patients affected by CPPS and 80 healthy controls who were asked to complete the
Arabic version of the NIH-CPSI. The translation was performed by a group
consisting of an andrologist and professional translators. Psychometric data were
collected. RESULTS: Of the 160 subjects enrolled, 82 (50 patients and 32
controls) completed the study. The total Arabic NIH-CPSI scores and the scores of
each subscale differed significantly between the two groups with good
discriminant validity. The questionnaire had also a high internal consistency.
CONCLUSION: The present study provides the Arabic version of the NIH-CPSI and
recognizes it as a valid and reliable tool in the assessment of local patients
with CPPS.
PMID- 17033211
TI - Is the determination of the soluble interleukin-2 receptor after application of
interleukin-2 receptor antibodies still appropriate for immunological monitoring
after renal transplantation?
AB - INTRODUCTION: The use of monoclonal antibodies against the alpha-chain of the
membrane-bound interleukin-2 receptor (IL-2Ralpha) as immune suppressants causes
characteristic changes in the levels of soluble interleukin-2 receptor (sIL-2R)
in serum and urine. METHODS: 38 kidney transplant patients were included in this
study. 28 of them received an induction therapy with the IL-2R antibody
basiliximax (Simulect) in addition to standard immunosuppression, 10 patients
constituted the control group. RESULTS: Time courses of sIL-2R levels of Simulect
patients with and without complications after transplantation have been compared.
It turned out that of a total of 18 cases with complications 15 cases could be
identified by their elevated sIL-2R levels, which corresponds to a sensitivity of
83%. CONCLUSION: Acute rejection, CMV infection, extrarenal bacterial infection
and pyelonephritis in the transplant all cause a significant increase of the sIL
2R level even after application of Simulect.
PMID- 17033212
TI - Upper urothelial tumors in emigrants from Balkan endemic nephropathy areas in
Serbia.
AB - AIM: The aim of the study was to investigate upper urothelial tumors (UUT) in
emigrants from Balkan endemic nephropathy (BEN) areas in Serbia and compare them
with UUT from both endemic and nonendemic areas. MATERIALS AND METHODS: A total
of 1,121 patients from the state cancer database, between 1960 and 1998, were
investigated. Sixty of them were emigrants from BEN areas. RESULTS: UUT in
emigrants from BEN areas occurred after 21.7+/-9.9 years (median 20) spent in a
rural environment. The time spent outside of the BEN regions was 33.2+/-12.8
years (median 31, range 10-72). Age at surgery was 55 years (range 31-89). In
emigrants from BEN areas, there was a significant association of other diseases
with UUT: renal failure in 63%, bladder tumors in 23.3% and bilateralism in 6.7%
of the patients. Bilateralism was statistically more frequent in emigrants from
BEN areas (p=0.04), as were low-grade tumors (p=0.03). There was no statistical
difference in tumor stage between patients from BEN areas and from outside of
them. Relatives of the emigrants from BEN areas were also affected by BEN, UUT
and both of them (33%). CONCLUSIONS: It is concluded that hereditary as well as
environmental factors are important for the expression and evolution of the
disease. An early period of life spent in the endemic region seems important for
the later development of UUT in emigrants from BEN regions. Different time spans
spent in the endemic region have no effect on the age of appearance of UUT.
PMID- 17033213
TI - Comparison of ileal conduit and transureteroureterostomy with ureterocutaneostomy
urinary diversion.
AB - INTRODUCTION: We compare the postoperative early and late complications of
patients who had undergone ileal conduit (IC) urinary diversion and
transureteroureterostomy (TUU) with ureterocutaneostomy (UC) urinary diversion
during the same interval and by the same surgeons. MATERIALS AND METHODS: Between
1992 and 2004, we performed TUU with UC urinary diversion in 27 men and 7 women
(group I) and ileal conduit urinary diversion in 57 men and 10 women (group II).
The mean age of the TUU with UC diversion and the ileal conduit patients was 57+/
11.2 (range 51-76) and 64+/-12.6 (range 54-76) years, and the mean follow-up was
37 (range 14-52) and 56 (range 14-72) months, respectively. The 6F or 8F stents
were used routinely. RESULTS: Of 34 TUU with UC cases 8 (23.52%) had early
postoperative complications and 2 (5.88%) had early reoperation rates, whereas 11
(16.42%) of 67 ileal conduit cases had early postoperative complications and 4
(5.97%) had early reoperation. The mean hospital stay was 7 (range 5-25 day) and
11 (range 7-34 day) days for each group, respectively. Of the TUU and UC cases, 6
(17.64%) had late complications and 3 had (8.82%) late reoperation, whereas 14
conduit cases (20.89%) had late complications and 6 had (8.9%) late reoperation.
Early postoperative complications were defined as those that occurred before
hospital discharge or within 30 days from the date of surgery and late
complications were defined as those occurring greater than 30 days from the date
of surgery as previously described. In group I, the mean operative time was 170
min (range 120-325) compared with 260 min (range 170-473) in group II. The mean
blood loss in group I was 474 ml (range 250-1,400) and 589 ml (range 300-1,700)
in group II (p>0.05). CONCLUSIONS: Our results suggest that patients undergoing a
TUU and UC diversion have no additional risk of reoperation and the TUU with UC
urinary diversion is a safe procedure with postoperative early and late
complications.
PMID- 17033214
TI - Are lower urinary tract symptoms associated with erectile dysfunction in aging
males of Taiwan?
AB - INTRODUCTION: This study was conducted to evaluate the relationship between lower
urinary tract symptoms (LUTS) and erectile dysfunction (ED) in aging males of
Taiwan. PATIENTS AND METHODS: A free health screening for aging males (>or=45
years old) was conducted in Kaohsiung Medical University Chung-Ho Memorial
Hospital in August 2004. LUTS and ED were assessed by validated symptom scales:
the International Prostate Symptom Score (IPSS) and the International Index of
Erectile Function-5 (IIEF-5). The subjects also completed a health and
demographics questionnaire and underwent detailed physical examination, serum
prostate-specific antigen level determination, and transrectal ultrasonography.
RESULTS: The final study population consisted of 141 patients with a mean age of
59.8 years. The severity of LUTS and ED increased with age. After controlling for
comorbidities, age (p<0.001) and IPSS score (p<0.001) were significantly
associated with the IIEF-5 score. Furthermore, men with moderate to high IPSS
scores were more likely to have ED as compared with those with mild symptoms
after age adjustment (age-adjusted odds ratio 3.27, p=0.002). CONCLUSIONS: ED and
LUTS are highly prevalent in our study population, and this prevalence increases
with age. ED is significantly associated with the severity of LUTS after
controlling for age and comorbidities. These results highlight the clinical
importance of evaluating LUTS in patients with ED and the need to consider sexual
issues in the management of patients with benign prostatic hyperplasia.
PMID- 17033215
TI - Hypoxia-inducible factors HIF-1alpha and HIF-2alpha expression in bladder cancer
and their associations with other angiogenesis-related proteins.
AB - Hypoxia-inducible factors (HIF-1alpha and HIF-2alpha) are closely related protein
complexes that activate transcription of target genes in response to hypoxia. The
immunohistochemical expression of these two proteins was investigated in 144
bladder cancer tissue samples and correlated with standard clinicopathological
features, in order to elucidate their prognostic significance. We also evaluated
their possible associations with other angiogenesis related markers such as
microvessel density (MVD), vascular endothelial growth factor, thymidine
phosphorylase, tenascin, fibronectin, p53 and bcl-2 to further clarify their
implication in tumor stroma vascularization. Nuclear HIF-1alpha expression in
tumor cells was detected in 57.1% of the cases. A trend of correlation of this
expression with poorly differentiated tumors was observed. In addition, HIF
1alpha expression was positively correlated with stromal cells thymidine
phosphorylase expression. Tumors that were progressed in muscle-infiltrating
disease showed a higher HIF-1alpha expression. A higher HIF-1alpha expression was
also observed in tumors with an in situ component. In tumor cells, low HIF-2alpha
expression was observed in 6.3%, moderate in 31.9% and high in 61.8% of the
cases. A trend of correlation of this expression with MVD was observed. In
addition, HIF-2alpha expression was positively correlated with thymidine
phosphorylase and fibronectin expression. A lower HIF-2alpha expression was
detected in tumors that recurred earlier in univariate methods of analysis. HIF
2alpha was expressed in tumor stroma associated cells in 53.5% of specimens and
was correlated with advance tumor stage, thymidine phosphorylase and tenascin
expression. There was no statistically significant difference in the expression
of both HIF-1alpha and HIF-2alpha between primary and recurrent tumors. In
multivariate analysis including T stage, T grade, multifocality and T size, both
HIF-1alpha and HIF-2alpha expression were not considered dependent in the
prediction of recurrence or progression. In conclusion, the results of the
present study indicate that HIF-1alpha and HIF-2alpha expression may help to
predict recurrence or progression to muscle invasive disease but not as
independent prognostic factors. In addition, the expression of HIF-1alpha and HIF
2alpha, appear to play a role in bladder cancer, vascularization possibly and in
cooperation with other angiogenic factors.
PMID- 17033216
TI - Effects of propylthiouracil on testicular tissue in undescended testes of newborn
rats.
AB - AIM: The most important goal in the treatment of cryptorchidism is to preserve
the potential for fertility. This experimental study was performed to investigate
the effect of propylthiouracil (PTU) on the undescended testes (UTs) of newborn
rats. MATERIALS AND METHODS: The experimental cryptorchidism model in newborn
male rats consisted of 4 groups. The groups A (control) and B (PTU) underwent no
surgical intervention, whereas in groups C (UT only) and D (treatment) UTs were
produced by dissecting and suturing the future right scrotal area. In groups D
and B, 0.1% (w/v) PTU was added to the drinking water of mother rats between 2
and 24 days. At the end of the 90th day rat body weights, testicular weights,
Johnsen tubular biopsy scores (JTBSs), seminiferous tubule diameters (STDs),
testosterone, and thyroid hormone levels were measured. Mann-Whitney U test was
used for statistical analysis. RESULTS: Mean testicular weight was similar
between groups A, B and D, and statistically lowest in group C. Mean body weight
was statistically higher in groups A and C compared with groups B and D. Mean
testosterone levels showed no statistical difference between the groups. Mean
JTBSs were statistically higher in groups A and B compared with groups C and D.
The value in treatment group D was statistically higher compared to group C
(p<0.05). Mean STDs were statistically lowest in group C compared to other groups
(p<0.05). No difference was found between groups A, B, and D (p>0.05). Both the
mean free triiodothyronine and free thyroxine values between groups A and C and
between groups B and D were similar. The values in groups A and C were
statistically higher than those of groups B and D (p<0.05). CONCLUSION: PTU
induced transient hypothyroidism in the newborn rat UT model shows protective
effects on testicular growth parameters.
PMID- 17033217
TI - Pumpkin seed oil and phytosterol-F can block testosterone/prazosin-induced
prostate growth in rats.
AB - INTRODUCTION: This study was undertaken to investigate the effects of pumpkin
seed oil alone or combined with Phytosterol-F on testosterone/prazosin-induced (T
P) prostate growth in rats. MATERIALS AND METHODS: Forty adult Wistar rats were
divided into five groups, including: one control group, rats treated with vehicle
only, one group treated with T-P, and two groups of T-P-treated rats, one
receiving orally pumpkin seed oil alone and one group receiving orally pumpkin
seed oil combined with Phytosterol-F. Two weeks later, the prostatic weight-to
body weight ratio was determined after sacrifice. The total protein concentration
was measured by using a protein assay. Some ventral prostatic tissues were
histologically examined after hematoxylin-eosin staining. RESULTS: Histological
sections of the ventral prostate showed that the architecture of the prostate
glands became hyperplastic in the T-P rats, but not in the control or vehicle
treated animals. As compared with the control or vehicle group, T-P rats had a
significantly higher prostatic weight-to-body weight ratio for the ventral
prostate (p=0.05 and p=0.007, respectively), but not for the dorsolateral
prostate (p=0.53 and p=0.73, respectively). The T-P rats had significantly higher
protein levels within both lobes (ventral lobe, p=0.02 and p<0.0001,
respectively; dorsolateral lobe, p=0.06 and p=0.005, respectively). As compared
with the T-P-alone rats, the TP rats treated with pumpkin seed oil alone or
pumpkin seed oil combined with Phytosterol-F had a significantly lower weight
ratio for the ventral prostate (p=0.01 and p=0.004, respectively) and
significantly lower protein levels within both lobes (p=0.03 and p=0.003,
respectively; p=0.007 and p=0.002, respectively). In addition, Phytosterol-F had
some additive effect on the total protein synthesis within the ventral prostate
(p=0.02). CONCLUSION: Pumpkin seed oil alone or combined with Phytosterol-F can
block the T-P-induced increases in prostatic weight-to-body weight ratio and
protein synthesis.
PMID- 17033218
TI - Long-term influence of prepubertal testicular torsion on spermatogenesis.
AB - PURPOSE: To study the influence of prepubertal unilateral testicular torsion on
spermatogenesis postpubertally. METHODS: Sixty prepubertal SD male rats were
divided into 6 groups. In each group, animal suffered different courses of
unilateral testicular torsion including sham operation, 2- and 6-hour-long
torsion, and permanent torsion. Salvia miltiorrhiza was injected as a remedy to
release the I/R injury in the 2- and 6-hour-long torted groups. Postpubertally,
the percentage of DNA content of haploid cells in the testes was determined
individually. RESULTS: The percentage of haploid cells in the sham operation
group was 76.5+/-1.9%. The number decreased in every other group (p<0.01).
Comparing with the same course of torsion, Salvia miltiorrhiza injection could
improve the percentage of haploid cells (p<0.01). In the permanent unilateral
testicular torted group, the percentage was nearly zero (0.4+/-0.2%).
CONCLUSIONS: Prepubertal unilateral testicular torsion induces decreased
spermatogenesis postpubertally. The result takes place in the bilateral testes.
Salvia miltiorrhiza, as an antioxidant remedy, could relieve the injury which
manifests improved spermatogenesis.
PMID- 17033219
TI - Primary bladder dermoid: a case report and review of the literature.
AB - Bladder dermoid is a rare presentation. Diagnosis of this case was made
cystoscopically and confirmed histopathologically. Complete excision was possible
endoscopically. This is the 3rd case report from the Indian and Asian
subcontinent.
PMID- 17033220
TI - A 7-year history of an intratesticular mass: patient description and review of
the literature about dermoid cysts of the testis.
AB - A dermoid cyst is a particular form of a cystic teratoma. In the testis, it is
very rare, with only a few cases reported in world literature. A 19-year-old
patient come to our attention with a 7-year history of an intratesticular cystic
mass. Sonography showed a large hypoechoic solid mass. The tumour markers alpha
fetoprotein, beta-human chorionic gondatotrophin, and lactate dehydrogenase were
negative. Chest X-ray was negative. He underwent surgical exploration of the
right testis and enucleation of the mass with testis preservation. At 14 month of
follow-up, the patient had no complications and no recurrence of the lesion.
Surgical enucleation is the treatment of choice in consideration of hormonal,
psychological, and reproductive aspects. Orchiectomy should have been the
treatment of choice, if the mass had substituted all testicular parenchyma and if
there had been some malignant transformations.
PMID- 17033221
TI - The unbreakable bladder stone--Munchhausen's tale.
AB - A wide range of intra-vesical foreign bodies have been described in the
literature. Causes include iatrogenic, migration from adjacent organs,
penetrating injuries and self-insertion, either due to eroticism, inquisitiveness
or as a result of a psychiatric illness. We present an unusual case of fictitious
bladder stones that proved unbreakable using all standard endourological
techniques.
PMID- 17033222
TI - Intermittent ureteral herniation--rare cause of flank pain.
AB - Ureteral herniation is rare and difficult to diagnose, especially when
intermittent, and ureterocystoneostomy using the psoas hitch or boari flap
techniques have so far been used as therapeutic options. We describe ureterolysis
in two cases as a successful alternative approach.
PMID- 17033223
TI - [Problems associated with molecular targeted drugs for cancer].
AB - Molecular targeted drugs have been developed and have come to play a part in the
standard treatment of cancers. However, issues such as the optimum dose,
selection of patients, and verification of the molecular targets remain to be
discussed, because unexpected clinical problems related to the clinical efficacy,
adverse events, and development of resistance have appeared. Therefore, proof of
principle (POP) studies and pharmacodynamic or pharmacogenomic research to
explore new bio-markers for the drugs are essential for clinical progress. On the
other hand, the higher cost of development and care must also be discussed as new
problems.
PMID- 17033224
TI - [Reasons for the increased incidence of skin cancer].
AB - The cutaneous malignancies with an increasing incidence in Japan are squamous
cell carcinoma, basal cell carcinoma, and malignant melanoma. As a precancerous
state or early lesion, actinic keratoses also deserve attention. According to a
nationwide questionnaire survey (responses from 94 centers), basal cell carcinoma
has the highest incidence and accounts for nearly 50% of all skin malignancies,
followed by squamous cell carcinoma (31%) and malignant melanoma (21%). The
number of cases of each tumor has grown annually, and comparison of the percent
increases between 1987 and 2001 shows an increase of about 1.5-fold for basal
cell carcinoma or 1.7-fold for squamous cell carcinoma or malignant melanoma.
Supported by a Grant-in-Aid for Cancer Research from the Ministry of Health,
Labor and Welfare, the Malignant Skin Tumor Research Group has been investigating
the factors behind these increases by detailed statistical analysis of data
obtained from 1987 onwards from designated centers (19-22 centers). Numerous
factors have been suggested by this research, but the most important was
concluded to be ultraviolet radiation.
PMID- 17033225
TI - [Melanoma].
AB - The definition of the TNM classification and staging system of malignant melanoma
have been fundamentally revised. Moreover, several clinical guidelines for the
management of this neoplasm were recently proposed. Advances in surgical
procedures are excision of primary lesions with narrow margin and introduction of
sentinel node biopsy, which contribute to maintain the good quality of life of
patients. The significance of high-dose interferon-alpha as adjuvant therapy is
still controversial. No effective chemotherapy or biotherapy has been established
to date, however, interesting new findings were recently reported in the fields
of immunotherapy and molecular targeting therapy.
PMID- 17033226
TI - [Squamous cell carcinoma].
AB - Squamous cell carcinoma of the skin is common skin malignancy arising from
malignant proliferation of the keratinocytes of the epidermis. Chronic exposure
to ultraviolet radiation in sunlight is the most important risk factor for
squamous cell carcinoma. Early diagnosis and appropriate treatment provide the
best opportunity to cure cutaneous squamous cell carcinomas. Although it is
locally invasive, squamous cell carcinomas usually remain localized and can be
cured by a variety of techniques. Surgical excision is the most broadly used
treatment for high-risk squamous cell carcinoma. It is well-tolerated, extremely
effective, and the completeness of the procedure can be evaluated through
histologic assessment of the specimen's margins. About 10 percent of squamous
cell carcinomas in Japan spread to regional lymph nodes or more distant sites
with a relatively poor outcome. Five-year cure rates are reported to be 85 to 80
percent for Japanese patients with squamous cell carcinomas, respectively.
Recommendations for surgical margins vary depending upon the risk of local
recurrence, especially; squamous cell carcinomas with perineural extension also
need more extensive procedures. Patients with clinically enlarged lymph nodes may
require radiographic imaging, fine needle aspiration, or lymph node biopsy.
Depending upon the results of these tests, regional lymph node dissection may be
done. Recently the sentinel lymph node biopsy technique is being evaluated for
its ability to detect microscopic involvement in patients with high-risk patients
who have no clinical evidence of lymph node metastasis. The occurrence of
regional lymph node metastases places the patient at increased risk for the
subsequent development of distant metastases. Distant metastases are associated
with a markedly increased risk of disease-related mortality. Systemic
chemotherapy has been to limited benefit in patients with disseminated squamous
cell carcinoma patients. In Japanese patients with distant metastases, the five
year survival rate is about 10 percent. The ability of current chemotherapy
protocols to increase the cure ratio in squamous cell carcinoma is still
controversial.
PMID- 17033227
TI - [Basal cell carcinoma].
AB - Basal cell carcinoma (BCC) is the most common skin cancer. It tends to be locally
invasive but rarely metastasizes. Dermoscopy has been reported as a useful in
vivo method for the accurate clinical diagnosis of BCC. The first-line treatment
for BCC is surgical excision, however, clinical trials of non-surgical treatment
modalities such as topical imiquimod and photodynamic therapy have recently been
published in the English literature, and are gradually being introduced into
Japan. Although clinical practice guidelines for the management of BCC have been
already published in several countries, original guidelines for Japan are
required in light of clinical and ethnic differences.
PMID- 17033228
TI - [Extramammary Paget's disease].
AB - The treatment strategy for extramammary Paget's disease depends on the presence
of metastasis. For the group of patients with primary tumor limited to the
epidermis, the aim of treatment is local control by precise detection of the
tumor margin. For patients without indications for surgery, radiotherapy or
photodynamic therapy would be the treatment of choice. On the other hand, the
prognosis of patients with distant metastases is desperate. Although a limited
response to combination chemotherapy was observed, no survival benefit has been
proven yet. New modalities of treatment such as molecular targeting drugs and
hormonal therapy are expected.
PMID- 17033229
TI - [Multicenter phase II trial of thrice-weekly docetaxel and weekly trastuzumab as
preoperative chemotherapy in patients with HER 2-overexpressing breast cancer-
Japan East Cancer Center Breast Cancer Consortium (JECBC) 02 Trial].
AB - The efficacy and safety of combination therapy of 4 cycles with docetaxel 70
mg/m(2)every 3 weeks and trastuzumab as primary chemotherapy for operable breast
cancer was determined in 21 patients (pts) by assessing the pathological complete
response (pCR) rate, clinical response rate (RR), breast conservation surgery
(BCS) rate and toxicities. To date, 19 pts have completed surgery. The pCR rate
was 21% [95% CI 6%-46%] . The overall RR was 90% [95% CI 67%-99%] , with 5 CR, 12
PR, 2 SD and 0 PD. Grade 3 or 4 adverse events were leukopenia 48%, neutropenia
67%, hemoglobin 5%, and febrile neutropenia 10%. All non-hematological toxicities
were mild and manageable. The pCR rate is not as low as that achieved in previous
international studies. The combination of docetaxel and trastuzumab was a well
tolerated and very active regimen for the treatment of patients with HER 2
overexpressing operable breast cancer. This regimen promises to be one of the
leading future treatments for progressive breast cancer.
PMID- 17033230
TI - [Adjuvant doxorubicin and cyclophosphamide followed by weekly paclitaxel for
Japanese women with node-positive breast cancer: a multi-institutional
feasibility study in a variety of practice settings in Kyushu].
AB - We evaluated the feasibility of doxorubicin plus cyclophosphamide (AC) followed
by weekly paclitaxel (wT) as adjuvant therapy for node-positive breast cancer in
a variety of practice settings. Forty-seven patients received AC at either doses
of 40 mg/m(2)+400 mg/m(2) (A(40)C(400), 33 patients) or 50 mg/m(2)+500 mg/m(2)
(A(50)C(500), 14 patients) every 3 weeks for 4 cycles followed by wT at a dose of
80 mg/m(2)for 12 cycles with a week pause after 3 consecutive weekly
administrations. Mean relative dose-intensities were 98.8% for A(40)C(400), 90.7%
for wT after A(40)C(400), 91.3% for A(50)C(500), and 89.2% for wT after
A(50)C(500). Grade 4 toxicity included neutropenia (3.0% for A(40)C(400), 14.3%
for A(50)C(500)). Grade 3 toxicity included neutropenia (18.2% for A(40)C(400),
28.6% for A(50)C(500), 6.7% for wT), thrombocytopenia (2.2% for wT),
nausea/vomiting (6.1% for A(40)C(400)), anorexia (3.0% for A(40)C(400), 2.2% for
wT), fatigue (3.0% for A(40)C(400)), AST/ALT elevation (7.1% for A(50)C(500)),
allergic reaction (4.4% for wT). There were six (12.8%) treatment
discontinuations, including two allergic reactions to paclitaxel. AC followed by
wT can be administered safely in the community at doses of 50 mg/m(2), 500
mg/m(2), and 80 mg/m(2), respectively,with minimal toxicity.
PMID- 17033232
TI - [Therapeutic efficacy of capecitabine on advanced and recurrent breast cancer
with special reference to time to progression].
AB - We investigated 29 patients with advanced and recurrent breast cancers who
underwent capecitabine therapy in the department. Patients'backgrounds: 41-89
years of age (median, 57 years of age). Advanced breast cancers, 5; recurrent
breast cancers, 24. PS< or =2 in 18 cases and PS 3< or =in 11 cases. Eighty-six
percent of patients were positive for ER and/or PgR. Multiorgan metastases
occurred in 22 cases; bone metastases, 22 cases; lymph node metastases, 12 cases;
skin metastases, 11 cases; lung metastases, 10 cases. The rate of patients who
received chemotherapy was 93%, and the rate of those who received
endocrinotherapy was 90%. Therapeutic response rate was CR in 1 case, PR in 5
cases, long SD in 5 cases, SD in 10 cases and PD in 8 cases, indicating a
response rate of 20.7% and a clinical benefit rate of 37.9%. Time to progression
(TTP) was 1-15 months (the median time, 4 months). Overall survival time (OS) was
2-23 months (median length, 12 months). OS was significantly longer in patients
who had therapeutic effects than in patients with no such effects. TTP was
significantly longer in patients who had therapeutic effects and in those who had
longer SD than in patients with no such effects. OS was significantly longer in
patients who had TTP of 6 months or longer. Clinical benefit (presence vs.
absence) and PS (< or =2 vs. 3< or =) were independent factors affecting TTP.
Capecitabine is expected to prolong the length of survival in patients who are
able to continue treatment for 6 months or longer.
PMID- 17033231
TI - [A randomized controlled study comparing uracil-tegafur (UFT)+tamoxifen (UFT+TAM
therapy) with cyclophosphamide+adriamycin+5-fluorouracil (CAF therapy) for women
with stage I , II, or IIIa breast cancer with four or more involved nodes in the
adjuvant setting].
AB - We performed a controlled study to compare the response to cyclophosphamide
(CPA), adriamycin (ADM), and fluorouracil (5-FU) (CAF therapy) with that to
uracil-tegafur (UFT) plus tamoxifen (TAM) (UFT+TAM therapy), when given as
postoperative adjuvant therapy to women with breast cancer. The patients were
registered from September 1991 through February 1995 at 51 institutions in the
Kinki district of Japan. All patients had stage I, II, or IIIa breast cancer with
four or more lymph-node metastases and underwent mastectomy. CAF therapy and
UFT+TAM therapy were started within 4 weeks after surgery. CAF therapy consisted
of CPA (100 mg/day) on days 1 to 14, followed by 2 weeks of rest, plus ADM (20
mg/m(2)/day) on days 1 and 8 and 5-FU (300 mg/m(2)/day) on days 1 and 8. A total
of 6 courses were delivered. UFT+TAM therapy consisted of 3 years of UFT (400
mg/day) plus TAM (20 mg/day), given daily. CAF therapy and UFT+TAM therapy were
each assigned to 82 patients. The 5-year survival rate was significantly higher
in the UFT+TAM group (82.1%) than in the CAF group (66.2%; p=0.04, logrank test).
The 5-year relapse-free survival rate was higher in the UFT+TAM group (61.8%)
than in the CAF group (46.3%; p=0.07, logrank test). As for adverse events, the
rates of leukopenia, anorexia, nausea and vomiting, general malaise, and hair
loss were lower in the UFT+TAM group than in the CAF group. These results suggest
that long-term treatment with UFT+TAM may be a useful alternative adjuvant
therapy for the management of breast cancer, especially in elderly patients.
PMID- 17033233
TI - [Prolonged survival of gefitinib treatment in patients with advanced and
previously treated non-small cell lung cancer].
AB - The purpose of this study was to evaluate the survival outcome in patients with
advanced and previously treated non-small cell lung cancer given gefitinib (GEF)
at our institution. We reviewed the clinical records of 70 Japanese
patients,among whom 33 received several chemotherapy treatment modalities
including GEF monotherapy (GEF group), and the other 37 were given several
chemotherapy treatment modalities without GEF monotherapy (non-GEF group). The
median survival time (MST) after second-line chemotherapy in the GEF group was
527 days with 1-year and 2-year survival rates of 59% and 26%, respectively. The
MST in the non-GEF group was 175 days with 1-year and 2-year survival rates of
21% and 16%, respectively. Overall survival after second-line chemotherapy in the
GEF group was significantly longer than in the non-GEF group (hazard ratio 1.93;
95% confidence interval 1.15-3.53, p=0.014). In our limited clinical experience,
chemotherapy treatment including GEF monotherapy appeared to have longer survival
than non-GEF treatment.
PMID- 17033234
TI - [Effectiveness of preoperative chemoradiotherapy for advanced rectal cancer].
AB - To determine the pathologic effectiveness of preoperative chemoradiotherapy (CRT)
in patients with advanced rectal carcinoma, we reviewed clinical records of 76
patients who received preoperative pelvic radiation +/- chemotherapy. Since 2
patients refused operation and 2 died before surgery, 72 patients underwent
operation with a mean delay of 19.9 days after completion of irradiation.
Pathologic tumor regression grade (Grade 0-3) was determined by the amount of
viable tumor versus necrosis and fibrosis. Grade 0, 1 a, 1 b, 2, and 3 (pCR) were
observed in 0%, 25.0%, 38.9%, 27.8% and 2.8% of patients, respectively. The
pathologic response (PR) rate was 75.0% when PR was defined as greater than grade
1 b (tumor regression more than 1/3). Downstaging was observed in 35.8% of
patients, in which 5-year overall survival was significantly better than in
patients without downstaging (90.0% vs. 50.1%, p<0.05). No correlation could be
observed between PR and downstaging. CRT is a useful tool with a high PR rate in
patients with advanced rectal cancer. More accurate and careful clinical staging
is important to select adequate candidates for CRT. Multi-institutional clinical
trials as well as standardizing the surgical procedure including LN dissection
are required to validate the advantages of CRT for Japanese patients.
PMID- 17033235
TI - [Combined chemotherapy with weekly paclitaxel and carboplatin for recurrent and
refractory epithelial ovarian cancer--phase I study].
AB - The current initial standard chemotherapy for advanced ovarian cancer is a
regimen with a combination of platinum and taxane. However, the 5-year survival
rate remains at 40% or lower, and the recurrence rate is as high as 70-80%.
Second-line chemotherapy for recurrent cases has not yet been established. We
conducted a phase I study of combined chemotherapy with paclitaxel (TXL) and
carboplatin (CBDCA) administered weekly for recurrent and refractory ovarian
cancer. The subjects were patients with a histopathologically confirmed diagnosis
of malignant epithelial ovarian cancer, with recurrent or refractory disease
after the initial chemotherapy. TXL was administered at escalating concentrations
up to 60-100 mg/m(2), while the dose of CBDCA was fixed at an AUC of 2. In regard
to the dosing schedule, premedication was performed as defined before TXL
administration, and TXL and CBDCA were administered, in that order, by
intravenous infusion for over at least 1 hour. The 4-week period, including the
administration of both drugs on Day 1, 8, and 15, was regarded as one course of
treatment. No cases developed grade 4 hematoxicity, but leukopenia and
neutropenia occurred. All cases of leukopenia of step 4 and step 5 developed
grade 3 leukopenia. Grade 2 thrombocytopenia was one example at a low rate. Non
hematological toxicity included neuropathy, arthralgia and muscle pain, but none
of the patients developed grade 3 or 4. The response rate was 41.7% (5/12). The
response rate of cases administered over TXL 80 mg was 66.7% (4/6). Based on
these results,the following dose schedule was recommended for planning and
designing a phase II study in the future: CBDCA AUC 2+TXL 80 mg/m(2) (Days 1, 8,
and 15 q 4 weeks).
PMID- 17033236
TI - [Case report of advanced breast cancer responding to capecitabine and trastuzumab
combination therapy].
AB - We conducted a concomitant administration of capecitabine (2,400 mg/day for 21
days followed by a 7-day interval) and trastuzumab (2 mg/kg weekly) to a 73-year
old female patient with impaired lower limb function diagnosed with bilateral
breast cancer. The patient had a complete response (CR) to pulmonary metastases,
and carcinoembryonic antigen (CEA) level had normalized from 46.4 ng/ml to 0.6
ng/ml. Left mastectomy was performed in order to control bleeding from tumors. No
adverse events attributable to medication were observed. The concomitant
administration of capecitabine and trastuzumab is a promising therapy with the
potential to greatly improve patient quality of life (QOL).
PMID- 17033237
TI - [A case of advanced gastric cancer with long-term survival treated by
chemotherapy and surgical cytoreduction].
AB - A 74-year-old man was revealed to have type 3 gastric cancer with lymph-node
metastasis in the third group (N 3) and liver metastasis (H 1). Since we regarded
a curative operation as impossible, we started preoperative chemotherapy using TS
1 plus irinotecan hydrochloride (CPT-11) on the premise that we would perform
surgical cytoreduction after the chemotherapy. After two courses of chemotherapy,
both the primary lesion and the liver metastasis were reduced in size, and the
paraaortic lymph-nodes disappeared. Subsequently, a distal gastrectomy (D 0,
curability C) was performed. The patient has been receiving postoperative
chemotherapy using TS-1 and paclitaxel as an outpatient for 2.3 years. Although
there is not enough evidence to support the benefit of surgical cytoreduction,
chemotherapy combined with surgical cytoreduction would improve the survival time
without deterioration of quality of life (QOL) in patients with advanced gastric
cancer. This combined therapy should be considered as one of the promising
strategies for advanced gastric cancer.
PMID- 17033238
TI - [A case of advanced gastric cancer--efficacy of combination therapy of
doxifluridine and weekly paclitaxel].
AB - A 65-year-old man underwent distal gastrectomy for advanced gastric cancer.
Histological examination revealed that a lymph node metastasis extended to the
para-aortic nodes. After operation, he was treated with TS-1 as first-line
chemotherapy. After 10 months of the first-line chemotherapy, the lymph node
swelling increased in size, and new lesions were detected. Then, the patient was
treated by combination therapy of doxifluridine and weekly paclitaxel. Weekly
paclitaxel administration (PTX 80 mg/m(2), 2 consecutive weeks, 1 week break) and
oral administration of doxifluridine (600 mg/m(2), 14 consecutive days) were
performed as the second-line chemotherapy. After 2 courses, abdominal CT scan
showed a remarkable reduction of the para-aortic lymph nodes. The second-line
chemotherapy was continued until the 7th course, then stopped without progression
of the disease, and the patient maintained good quality of life. PTX/5'-DFUR
combination therapy was thought to be an effective chemotherapy for advanced
gastric cancer.
PMID- 17033239
TI - [A resected case of advanced gastric cancer with multiple liver metastasis
responding to preoperative TS-1/CDDP chemotherapy].
AB - CASE: A 75-year-old man was admitted to our hospital with hematoemesis.
Gastrofiber-scopy revealed that type 3 gastric cancer was widespread in the
lesser curvature. Multiple liver metastases 5 cm in diameter were shown on CT. We
thought that the case was unresectable, and TS-1/CDDP chemotherapy was performed.
TS-1 (80 mg/body/day) was orally administered and CDDP at 20 mg/body/day by
intravenous drip infusion a week for 3 weeks followed by a drug-free 2 week
period as the first course. After the third course, the primary lesion and the
liver metastasis showed a partial response in terms of size. No serious drug
adverse reaction was observed. Since there was no longer any reduction of the
tumor, gastrectomy and coagulation therapy for liver metastasis were performed,
and he has been alive for 15 months without recurrence. Combined use of TS-1 and
CDDP is effective as neoadjuvant chemotherapy for advanced gastric cancer.
PMID- 17033240
TI - [Two metastatic colonic cancer patients successfully treated by combination
therapy of tegafur/uracil (UFT) and oral Leucovorin].
AB - Two metastatic colonic cancer patients were successfully treated by the
combination therapy of UFT plus oral Leucovorin (UFT/LV). UFT was administered
orally every eight hours at a dose of 300 mg/day in case of less than 1.20 m(2),
400 mg/day in case of between 1.20 and 1.70 m(2), 500 mg/day in case of over 1.70
m(2), and Leucovorin (75 mg/day) was simultaneously given for 28 consecutive days
and stopped for seven days. This cycle was repeated until the patients requested
the therapy be discontinued or a severe adverse reaction was observed. Case 1: A
79-year-old male had undergone sigmoidectomy for colonic cancer in 2001 and was
diagnosed with pulmonary metastases in August, 2005. His performance status (PS)
was grade 3. Case 2: A 61-year-old male with liver metastasis whose primary
colonic lesion was surgically resected. After 2 cycles of UFT/LV therapy, a good
partial response was achieved in both cases. Adverse effects were very mild,
indicating that this therapy was very safe and recommendable for the treatment of
metastatic colonic cancer patients with poor PS.
PMID- 17033241
TI - [A case of effective multidisciplinary treatment with hepatic resection for
synchronous multiple liver metastases from rectal cancer].
AB - A 56-year-old-man complained of abdominal pain, and was diagnosed as having
advanced rectal cancer with synchronous multiple metastatic liver cancer (H 3) in
July 1999. He underwent low anterior resection and hepatic partial resection (S
1, S 2+S 3, S 5, S 6, S 8) in August 1999. In addition, he underwent hepatic
arterial infusion chemotherapy (HAI) 6 times at ADM 30 mg+5-FU 1,000 mg+MMC 16 mg
between October 1999 and July 2000 for recurrent metastatic liver cancer. He has
survived more than 6 years after the initial surgery. Multidisciplinary treatment
with hepatic resection may well be a strategy for patients with multiple
colorectal liver cancer, even though H 3 type of metastasis.
PMID- 17033242
TI - [A case of advanced rectal cancer responding to oral UFT and Leucovorin-based
preoperative chemoradiation therapy].
AB - We report a case of a 44-year-old male with advanced lower rectal cancer that
showed a significant effect after preoperative chemoradiation therapy.
Preoperative radiation and chemotherapy included whole pelvis irradiation (30 Gy
in total), oral UFT (500 mg/day), and Leucovorin (75 mg/day) was administered
daily for 4 weeks. Consequently, the patient underwent a total pelvic
exenteration with lymph node dissection (D 3). Histopathological findings showed:
invasion to peritoneum(Ai); stage IIIa with n(-); and histological grading, Grade
2. Preoperative chemoradiation therapy appears to be effective for locally
advanced lower rectal cancer.
PMID- 17033243
TI - [Case report of a liver metastasis from rectal cancer achieving complete response
(CR) by a combination of intra-hepatic arterial infusion of irinotecan (CPT-11)
with degradable starch microspheres (DSM) and weekly high-dose intra-hepatic
arterial chemotherapy with 5-FU].
AB - A 67-year-old woman, who was diagnosed with rectal cancer and liver metastasis,
underwent a low anterior resection of the rectum in May 2004. Two months later,
the level of tumor markers increased and a CT scan revealed a 45 x 35 mm liver
metastasis in the S(8) segment. She was referred to our hospital for treatment of
the liver tumor. Intra-hepatic arterial infusion of irinotecan (CPT-11) and
mitomycin C (MMC) with degradable starch microspheres (DSM) was given in July
2004. Following this, a 34-week course of weekly high-dose intra-hepatic arterial
5-FU infusion (5-FU 1,000 mg/m(2)) was performed. In April 2005, the size of the
liver metastasis decreased, and the level of serum tumor marker normalized. A CT
and echo scan revealed a calcified tumor, and therefore all chemotherapy was
stopped. She was followed in the outpatient clinic, with no evidence of
recurrence for 12 months. This case suggests that the use of intra-hepatic
arterial infusion of CPT-11 and MMC with DSM is useful for the treatment of liver
metastases in colorectal cancer.
PMID- 17033244
TI - [A case of adenocarcinoma of unknown primary site successfully treated with
gemcitabine monotherapy].
AB - A 68-year-old female diagnosed with adenocarcinoma of unknown primary site (ACUP)
by biopsy of supraclavicular lymph node was admitted to our department because of
progressive dyspnea with cough. The diagnosis of multiple lung metastases and
malignant pleural effusion was made. Marked elevation of serum CA 19-9 and DUPAN
2 urged us to treat her as a case of pancreatic carcinoma. Gemcitabine
monotherapy yielded resolution of symptoms, decline in the level of tumor
markers, shrinkage of lung metastases, and disappearance of pleural effusion.
After 10 cycles, the chemotherapy was terminated. However, clinical deterioration
was observed two months later. The re-treatment with gemcitabine was started, and
a good response was obtained again. Gemcitabine monotherapy can be one of the
treatment options for ACUP.
PMID- 17033245
TI - [A case of squamous cell carcinoma of unknown primary site with involvement of
cervico-mediastinal lymph nodes successfully treated by chemoradiotherapy].
AB - A 70-year-old woman was admitted with cervicomediastinal lymph node metastases
from squamous cell carcinoma of unknown primary site (Sq-CUPS). The patient was
treated with 4 cycles of chemotherapy combining carboplatin and paclitaxel with
subsequent radiation therapy. After serial treatment, a partial response was
obtained, and the disease has not recurred for over 2 years. Chemotherapy with
carboplatin and paclitaxel followed by sequential radiation therapy was suggested
to be potentially useful for Sq-CUPS with involvement of cervicomediastinal lymph
nodes, although this group of patients is generally regarded to have a poor
prognosis.
PMID- 17033246
TI - [Colonic perforation in a patient treated with combination chemotherapy for
recurrent ovarian clear cell adenocarcinoma].
AB - BACKGROUND: Colonic perforation due to colitis is a known and reported side
effect of chemotherapy. CASE REPORT: A 53-year-old woman was treated with
combination chemotherapy of irinotecan plus cisplatin for a recurrent ovarian
clear cell adenocarcinoma. Steroid was also used for suspected interstitial
pneumonia. After two cycles of treatment, she developed a colonic perforation.
Emergency laparotomy was not performed because of poor performance status with
multiple lung metastases, pleural effusion and pericardial effusion. Colonoscopy
showed a perforated wall at the cecum, and a long tube with balloon was inserted
for occlusion. In addition, a peritoneal drainage tube was inserted. Oral intake
could be restarted for a while, but she died from tumor progression one and a
half months after the diagnosis of perforation. CONCLUSION: Non-surgical
management with peritoneal drainage and ileus tube was useful in this case of
colonic perforation for preserving oral intake and quality of life.
PMID- 17033247
TI - [A case of stage IVA intrahepatic biliary tract cancer successfully treated with
gemcitabine].
AB - We reported a case of non-resectable intrahepatic biliary tract cancer, treated
with Gemcitabine and oral anticancer drugs. A 45-year-old man was admitted to the
hospital due to abdominal distension and fatigue. CT scan revealed intrahepatic
biliary tract cancer in the left lobe, which had metastasized to both lobes.
Based on the diagnosis of non-resectable intrahepatic biliary tract cancer,
systemic chemotherapy using gemcitabine (GEM) was employed. One course of the
treatment consisted of 4 weeks. GEM 1,000 mg was administered once a week for 3
weeks followed by a week of no treatment. At the same time, the oral anti-cancer
drug (5'-DFUR 600 mg/day) was administered every day. After 4 courses of
chemotherapy, both the primary tumor and the hepatic metastasis were diminished,
and the serum level of CA19-9 was reduced to the normal value. Relief from the
abdominal distension allowed the patient to return to work. The chemotherapy was
continued by outpatient-clinic treatment, preserving the quality of life for 13
months. The present case shows that gemcitabine/5'-DFUR combination is well
supported in advanced unresectable biliary tract cancer.
PMID- 17033248
TI - [Two cases of advanced pancreatic cancer with cervical lymph node or liver
metastasis responding well to S-1 monotherapy].
AB - In two patients with advanced pancreatic cancer with cervical lymph node or liver
metastasis and no indication of pancreatic resection and radiotherapy, oral
treatment with S-1 (an anti-cancer agent of fluoropyrimidine derivative) exerted
high anti-tumor activity on the metastatic lesions. Both cases responded well to
this therapy in the late phase II study of S-1 in patients with advanced
pancreatic cancer designed to evaluate efficacy and safety. In Case 1 (with
cervical lymph node metastasis), the anti-tumor efficacy of this therapy was
evaluated as a partial response (PR) after the first four courses of treatment.
In Case 2 (with liver metastasis), the efficacy was evaluated as PR for overall
response. Thus, the therapy indicated excellent efficacy in both cases. No grade
3 or severe adverse event was noted in either of the two cases. In Case 1, grade
2 anemia, stomatitis, vomiting and fatigue, and some other mild events were
noted. When used as a systemic chemotherapy for metastatic pancreatic cancer,
oral treatment of S-1 is highly effective, tolerable and convenient in an
outpatient clinic. This drug is a promising way to improve and preserve the QOL
essential to long-term home care.
PMID- 17033249
TI - [Resolution of liver metastases in response to S-1 monotherapy in advanced
pancreatic cancer--a case report].
AB - We report a case in a late phase II clinical study investigating the efficacy and
safety of the oral fluoropyrimidine anticancer drug S-1. The drug proved
effective in a patient with inoperable advanced pancreatic cancer in whom
radiation therapy was not indicated. The antitumor effect after 4 courses was
rated excellent, with a target site (liver) evaluation of CR and overall
evaluation of PR. In particular, two liver metastases, measuring 18.7 x 15.4 mm
and 16.2 x 14.6 mm, respectively, both resolved, and S-1 was found to exert a
potent antitumor effect against metastases. Assessment of adverse events revealed
no grade 3 or 4 adverse reactions, and other adverse events were all mild. Based
on the above results, S-1 appeared to be effective against advanced pancreatic
cancer and showed excellent tolerability.
PMID- 17033250
TI - [Two patients effectively treated by S-1 monotherapy for metastatic pancreatic
cancer].
AB - We report two metastatic pancreatic cancer patients who showed marked tumor
shrinkage following administration of the oral fluorinated pyrimidine anticancer
drug, S-1. In the early phase II trial of S-1 for metastatic pancreatic cancer,
both patients showed a partial response (Japan Society for Cancer Therapy
Criteria): the reduction ratio of the tumor volume was 81.4% in the patient with
liver metastasis (Case 1) and 86.9% in the patient with lung metastasis (Case 2).
Case 1 showed grade 3 anorexia and decrease of the serum hemoglobin as severe
adverse effects, but the other adverse reactions were mild. Both patients could
be treated as outpatients. S-1 showed a promising antitumor effect and
tolerability in patients with metastatic pancreatic cancer, and it was also
considered to be beneficial for patients in terms of convenience of
administration, that is, by the oral route.
PMID- 17033251
TI - [Chemotherapy-naive advanced pancreatic cancer with multiple liver metastases
successfully treated by S-1 monotherapy--a case report].
AB - We report a patient with chemotherapy-naive advanced pancreatic cancer having
multiple liver metastases which dramatically responded to S-1, an oral
fluoropyrimidine. The patient was enrolled in the "Late Phase II Clinical Study
of S-1 in Patients with Advanced Pancreatic Cancer." Anti-tumor efficacy after
the first four courses of S-1 monotherapy was confirmed to be partial response
(PR) in overall response by Response Evaluation Criteria in Solid Tumors
(RECIST). Grade 3 neutropenia was observed, but no other severe toxicities were
noted. On the basis of the results of the late phase II clinical study, S-1 is a
promising agent for systemic chemotherapy against advanced pancreatic cancers
because of its excellent efficacy, high tolerability, and convenient route of
oral administration.
PMID- 17033252
TI - [Examination of the safety of docetaxel/cyclophosphamide combination therapy for
advanced recurrent breast cancer].
AB - In the treatment of recurrent breast cancer in patients previously treated with
anthracycline drugs, taxane drugs are generally used. This time, we
retrospectively studied the safety of docetaxel/cyclophosphamide combination
therapy (hereinafter referred to as TC therapy). Ten patients (mean age: 52.8
years old) were included in the study. Metastatic/recurrent sites included 3
skin, 2 each of contralateral breast, lung and bone, and 1 each of liver,
carcinomatous pleurisy and supraclavicular lymph node. Seven patients had a
history of anthracycline treatment. The patients received TC at doses of 60
mg/m(2) and 500 mg/m(2), respectively, every 3 weeks. With regard to adverse
events, non-hematotoxic events included alopecia in all the patients, generalized
malaise in 5, and abnormal nail in 1. Hematotoxic events were grades 2 and 3
decreased neutrophil count in 5 patients. One patient had grade 4 pyrexia
associated with oral candida. The patient was admitted and treated with fluid
replacement and granulocyte colony-stimulating factor (G-CSF). There were no
other patients in whom the treatment was prolonged or dosage was reduced due to
adverse reactions. TC therapy is considered to be a beneficial treatment method
in terms of safety since it can be instituted on an outpatient basis.
PMID- 17033253
TI - Central obestatin administration does not modify either spontaneous or ghrelin
induced food intake in rats.
AB - The isolation of ghrelin unveiled a new system implicated in food intake
regulation. The recently isolated hormone obestatin derives from the same
precursor of ghrelin and seems to perform opposite actions. It could be part of a
dual system connecting gut and brain to regulate energy homeostasis. The ability
of intracerebroventricular administration of obestatin to modify food intake was
evaluated. Obestatin had no effect on spontaneous food intake in both ad libitum
and food restricted rats. The obestatin injection was not able to antagonize the
ghrelin-stimulated increase in food intake either. In conclusion, the present
work does not support a role for obestatin on the regulation of food intake in
any model studied.
PMID- 17033254
TI - Obestatin inhibits feeding but does not modulate GH and corticosterone secretion
in the rat.
AB - Obestatin is a recently discovered 23 amino acids peptide derived from the
ghrelin gene. As opposed to ghrelin, obestatin was shown to inhibit food intake
in mice. The aims of this research were to study the effects of acute obestatin
treatment on feeding behavior in the rat and its effects on GH and corticosterone
secretion. Our results demonstrate that in young-adult male rats, obestatin
effectively blunts the hunger caused by short-term starvation. Obestatin did not
modify GH secretion in 10-day-old rats and did not antagonize the GH-releasing
effects of hexarelin. Moreover, obestatin administration had no effects on
spontaneous corticosterone secretion. In conclusion, these data demonstrate that
in young-adult male rats the newly discovered obestatin can inhibit feeding but
does not modify GH and corticosterone release in infant rats.
PMID- 17033255
TI - Endogenous hyperinsulinemic hypoglycemia: diagnostic strategies, predictive
features of malignancy and long-term survival.
AB - Diagnostic strategies, malignancy predictors and long-term survival were
retrospectively evaluated in patients with hyperinsulinemic hypoglycemia (64
insulinomas). Lower median glycemia was 30 (range 20-53) mg/dl [1.6 (1.1-2.9)
mmol/l] with concurrent insulin of 48 (13.2-217) microU/ml and 15 (2-46)
microU/ml measured by radioimmunoassay (RIA) and immunofluorimetric assay (IFMA),
respectively. All patients with insulinomas had a positive prolonged fast within
48 h. Sensitivity of localization methods was: ultrasonography (US) 23%, computed
tomography (CT) 28%, magnetic resonance imaging (MRI) 65%, endoscopic US 75%,
arteriography 38%, portal venous sampling 67%, selective arterial calcium
stimulation 67%, intraoperative US 94% and palpation 92%. Nine patients (14%) had
malignant insulinomas. Age at diagnosis (mean+/-SD, 53.8+/-19 vs 39.4+/-16.3 yr;
p=0.03), insulin (1372+/-730 vs 785+/-659% (percentage of the method's diagnostic
cut-off; 6 and 3 microU/ml for RIA and IFMA, respectively; p=0.007) and C-peptide
levels (9.8+/-2.9 vs 3.9+/-2.8 ng/ml (3.2+/-0.9 vs 1.3+/-0.9 nmol/l; p=0.006),
and tumor size (6.2+/-4.1 vs 1.5+/-0.6 cm; p=0.0002) were increased in malignant
insulinomas. C-peptide level above 6.1 ng/ml (2.0 nmol/l) had a 100% sensitivity
and 96% specificity, and tumor size above 2.6 cm yielded a sensitivity of 88% and
specificity of 100% in predicting malignancy. Survival of patients with malignant
insulinomas was significantly impaired (16 vs 100% at 5 yr; p=0.0000001). The
diagnosis of insulinoma can be made within 48 h of fasting. The association
between intraoperative US and palpation evidenced the tumor in 95% of the
patients. C-peptide and tumor size were reliable malignancy predictors.
PMID- 17033256
TI - Endogenous coenzyme A glutathione disulfide in human myocardial tissue.
AB - Besides its role as a mechanical pump, the human heart serves as an endocrine
organ, where known and as yet unknown hormones are produced. It is very likely
that these hormones play an important role in cardiovascular regulation. In this
study, a new endogenous vasoactive substance, coenzyme A glutathione disulfide
(CoASSG), was isolated and identified in myocardial tissue. Human myocardial
tissue was extracted with perchloric acid and fractionated by size exclusion-,
displacement-, anion-exchange- and reversed-phase chromatography. In one fraction
purified to homogeneity, CoASSG was identified by matrix assisted laser
desorption/ionization (MALDI) mass-spectrometry, post-source decay MALDI-mass
spectrometry and enzymatic structure analysis. Furthermore, CoASSG was also
isolated from human cardiac specific granules. CoASSG has potent vasoconstrictive
and proliferative effects. Therefore, CoASSG may affect myocardial function as an
endocrine or autocrine substance after being released from myocardial specific
granules.
PMID- 17033257
TI - Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as
compared to subacute thyroiditis.
AB - BACKGROUND: Two main forms of amiodarone- induced thyrotoxicosis (AIT) exist:
type 1 AIT is a condition of true hyperthyroidism developing in patients with pre
existing thyroid disorders, and usually requires thyroid ablative treatment. On
the other hand, type 2 AIT is a form of destructive thyroiditis occurring in
normal thyroids, the management of which usually consists in glucocorticoid
treatment. AIM: To assess the long-term outcome of thyroid function in a
prospective study of type 2 AIT patients, as compared to patients with De
Quervain's subacute thyroiditis (SAT). PATIENTS AND METHODS: Sixty consecutive
patients with type 2 AIT were evaluated during oral glucocorticoid treatment
(oral prednisone 30 mg/day, gradually tapered and withdrawn over a 3-month
period) and followed for 38+/-4 months (range 6-72) thereafter. Sixty consecutive
patients with SAT, referred to our Institutes during the same period and treated
with the same therapeutic schedule, served as controls. RESULTS: Type 2 AIT
patients were older (p<0.0001) and showed a larger male preponderance (M:F 3.6:1
vs 0.5:1, p<0.0001) than SAT patients. Mean serum free T4 (FT4) and free T3 (FT3)
concentrations at diagnosis were increased in both conditions, but higher in type
2 AIT than in SAT (FT4 47.6+/-18.8 and 29.6+/-8.3 pmol/l, respectively, p<0.0001;
FT3 15.4+/-7.0 and 11.2+/-3.0 pmol/l, respectively, p<0.001). Correction of
thyrotoxicosis was obtained in all patients in both groups, but restoration of
euthyroidism occurred earlier in SAT than in type 2 AIT (p=0.006). Ten type 2 AIT
patients (17%) and 3 SAT patients (5%, p<0.03) became permanently hypothyroid
after glucocorticoid withdrawal and required levothyroxine replacement.
CONCLUSIONS: A relevant proportion of type 2 AIT patients develop permanent
hypothyroidism after correction of thyrotoxicosis. Thus, periodic surveillance of
thyroid status is required after type 2 AIT.
PMID- 17033258
TI - Reduced levels of adiponectin in sleep apnea syndrome.
AB - BACKGROUND: To investigate adiponectin levels in an obese population with and
without obstructive sleep apnea syndrome (OSAS) and the acute modifications in
adiponectin after a whole-night control by auto continuous positive air pressure
(CPAP). METHODS: 46 obese subjects [22 males, 24 females, age 55.1+/-11.4 yr,
body mass index (BMI) 38.9+/-6.5 kg/m2]: 11 OSAS with apnea/hypopnea index (AHI)
from 10/h to 30/h, 14 OSAS with AHI >30/h and 21 without OSAS. Thirty-seven
normal weight healthy subjects (20 males, 17 females, age 31.3+/-9.5 yr, BMI
21.5+/-1.8 kg/m2). Serum adiponectin levels, biochemical parameters,
anthropometric measurements, pulmonary function, pulse-oxymetry and
polisomnography. RESULTS: The 3 groups of obese patients were comparable for
gender, BMI, age, fat mass, fat free mass, hip and waist circumference, waist-to
hip ratio (WHR), systolic and diastolic blood pressure and glycometabolic
parameters. Adiponectin levels were significantly reduced in obese patients
compared to healthy normal weight subjects (8.1+/-3.5 vs 11.3+/-4.8 microg/ml
p<0.001) In particular, adiponectin showed a trend to decrease according to the
severity of OSAS. No differences in adiponectin levels were found after a whole
night control by Auto CPAP. CONCLUSIONS: OSAS is associated with reduced levels
of adiponectin independently of insulin-resistance and BMI. These low adiponectin
levels may contribute to the increased mortality seen in such patients.
PMID- 17033259
TI - Hormonal control of inhibin B in men.
AB - Serum inhibin B (IB) and testosterone (T) levels, secreted by Sertoli cells (SC)
and Leydig cells (LC), respectively, are parameters of the functional state of
these cells. Whereas LC activity and, consequently, T secretion are regulated by
serum LH, factors regulating IB secretion by SC are still partially unknown.
There is evidence that under certain conditions such as puberty, aging or some
spermatogenesis defects, LH levels or Gn-independent factors might contribute to
regulating SC activity and IB secretion. Among these factors, GH and IGF-I as
well as PRL might have a role. Therefore, in order to explore the possible
effects of either LH alone and FSH alone or a combination of both Gn,
respectively, on SC function, IB plasma levels and spermatogenesis, we studied
their effects in 6 patients with hypogonadotropic hypogonadism (HH), whereas the
effects of GH on these parameters were studied in 6 men with panhypopituitarism
(PH). Finally, the possible effects of PRL on SC function and spermatogenesis
were studied in 6 patients with hyperprolactinemia (HPRL); 24 normal, fertile
adults served as control group. In men with HH, neither human chorionic Gn (hCG)
nor FSH, respectively, were able to increase serum IB after 3 months of therapy,
whereas combined Gn therapy for 24 months increased IB plasma levels and
stimulated spermatogenesis in 4 out of 6 hypogonadal men. In panhypopituitaric
men, GH added to the classical Gn therapy did not have an additional effect on
serum IB levels or spermatogenesis. Surprisingly, in our hyperprolactemic men, IB
plasma levels were increased and positively correlated (p<0.01) with serum PRL
levels, whereas normalization of the latter by cabergoline treatment caused a
decrease of IB levels and a moderate increase in T, LH and FSH. In conclusion,
the lack of SC response to FSH therapy alone, as opposed to the response to
combined Gn therapy, might indicate that normalization of serum T by hCG is
required to obtain IB secretion by SC. Addition of GH did not affect SC function,
serum IB levels or spermatogenesis. Finally, our data suggest that PRL plasma
levels might have a direct role on IB secretion, suggesting that the hypogonadism
found in patients with HPRL might be a consequence of both central (inhibition of
Gn secretion) and peripheral (stimulation of IB secretion) origin.
PMID- 17033260
TI - Iodine deficiency and goiter prevalence in Turkey after mandatory iodization.
AB - OBJECTIVE: The determination of (a) iodine deficiency, and (b) the relation
between the iodized salt consumption in the Isparta province of Turkey. METHODS:
Five hundred students between 6-11 yr of age were evaluated. With a
questionnaire, the subjects were asked whether they were using iodine-containing
salt or not. After their body weight and height were measured, thyroid glands
were examined with palpation, thyroid volumes were determined with
ultrasonography (USG), and urinary iodine concentration was analyzed. RESULTS:
The median urinary iodine concentration (UIC) of children was 7.00 microg/dl.
This value reveals that Isparta is a region with mild iodine deficiency. The
total goiter prevalence was 30.4% with palpation and 26% with USG. The goiter
prevalence by ultrasonography was 14.2% for the urban and 36.2% for the rural
areas. This difference was statistically significant (p<0.05). The rate of total
iodized salt consumption was 68%, which was not a satisfactory level. The
consumption of iodized salt in the urban areas was significantly higher than that
in rural areas (74 vs 62%, p<0.05). The median UIC value was 10.00 microg/dl in
urban areas compared to 5.00 microg/dl in rural areas. CONCLUSIONS: Our results
indicate that although Isparta is a region with mild iodine deficiency, goiter
prevalence remains a serious problem.
PMID- 17033261
TI - Intra-follicular leptin concentration as a predictive factor for in vitro oocyte
fertilization in assisted reproductive techniques.
AB - BACKGROUND: Granulosa-cells are able to produce and store leptin, suggesting that
this hormone is locally involved in the regulation of follicular growth. In this
study, the role of follicular fluid (FF) leptin concentration in predicting
oocyte fertilization and embryo quality was evaluated in 35 normogonadotrophic
women undergoing controlled ovarian stimulation (COS) for assisted reproductive
techniques. MATERIALS AND METHODS: Leptin concentration was measured in 47
consecutively collected FF in which a mature oocyte had been found during the
ovum pick-up. Embryos deriving from fertilized oocytes were submitted to quality
scoring systems. RESULTS: Mean leptin concentration was significantly higher in
FF whose oocytes showed 2 pronuclei (no. 25) when compared with those with no
evidence of fertilization (no. 22) at the 16-18 h check (26.0+/-6.1 vs 15.3+/
10.6 ng/ml, respectively, p<0.01). Follicular mean diameters were similar in the
two groups (21.4+/-3.4 and 21.0+/-5.1 mm, respectively). Logistic regression
analysis identified FF leptin levels as the best predictive parameter for oocyte
fertilization (p<0.001). When receiving operating characteristics curve was
employed, a FF leptin concentration of 20.25 ng/ml was the most reliable cut-off
in predicting fertilization of oocytes. FF with leptin concentrations higher than
this value (no. 27) had an oocyte fertilization rate of 85.7%. In contrast, FF
levels < or =20.25 ng/ml (no. 20) were associated with a rate of 16.7% (p<0.05).
No correlation emerged between FF leptin and the score attributed to 15 valuable
embryos at the zygote stage (r=-0.01) and at 48 h after insemination (r=0.1).
CONCLUSIONS: FF leptin levels are a better predictor of oocyte fertilization
success rates than follicular diameter. These results underline the relevance of
FF variables in developing methods for oocyte selection.
PMID- 17033262
TI - Saliva cortisol measurement: simple and reliable assessment of the glucocorticoid
replacement therapy in Addison's disease.
AB - No ideal parameter is available for assessment of the glucocorticoid replacement
therapy in Addison's disease. Serum cortisol day-curves can be used to monitor
the therapy, but this technique is cumbersome and expensive. We evaluated the
potential for saliva cortisol measurement in this setting. We found excellent
correlation between serum and saliva cortisol after oral intake of cortisone
acetate (no. 7) or iv administration of hydrocortisone (no. 4) (Pearson's R=0.83
0.98, p<0.002). A morning dose of 12.5 mg cortisone acetate yielded wide
interindividual variations in cortisol levels in saliva. Saliva cortisol
measurements were successfully adopted to evaluate and adjust doses in
outpatients. We conclude that cortisol measurement in saliva is practical and
reliable, and is preferable to serum cortisol measurement in the assessment of
the glucocorticoid replacement therapy. Our results confirm that only a minority
of patients require more than 12.5 mg of cortisone acetate (equivalent to 10 mg
hydrocortisone) in the morning to have sufficient cortisol levels during the
first part of the day.
PMID- 17033264
TI - Unusual association of adrenal pheochromocytoma and para-aortic neurofibroma in
pregnancy.
AB - The association of pheochromocytoma (PHEO) and pregnancy is uncommon and life
threatening for both the fetus and the mother. Early diagnosis and treatment is
essential to decrease maternal and fetal mortality and to differentiate the
disease from the more common pre-eclampsia. While medical treatment should be
started immediately after diagnosis, the timing of surgical treatment is still
debated. We describe the case of a 27-yr-old woman in the 18th week of pregnancy
who showed a biochemical pattern typical of PHEO and, by imaging studies, 2
tumors with the same characteristics: the first localized on the right adrenal
gland, the second at the right renal hilum. The patient underwent surgery because
of suspicion of malignant PHEO with local metastasis, while histology revealed a
rare association of a solitary PHEO and para-aortic neurofibroma, both tumors
embryologically deriving from a common cell precursor.
PMID- 17033263
TI - Assessment of serum IGF-I concentrations in the diagnosis of isolated childhood
onset GH deficiency: a proposal of the Italian Society for Pediatric
Endocrinology and Diabetes (SIEDP/ISPED).
AB - The diagnosis of GH deficiency (GHD) is based on the measurement of peak GH
responses to pharmacological stimuli. Pharmacological stimuli, however, lack
precision, accuracy, are not reproducible, are invasive, non-physiological and
some may even be hazardous. Furthermore, different GH commercial assays used to
measure GH in serum yield results that may differ considerably. In contrast to
GH, IGF-I can be measured on a single, randomly-obtained blood sample. A review
of the available data indicates that IGF-I measurement in the diagnosis of
childhood-onset isolated GHD has a specificity of up to 100%, with a sensitivity
ranging from about 70 to 90%. We suggest an algorithm in which circulating levels
of IGF-I together with the evaluation of auxological data, such as growth rate
and growth, may be used to assess the likelihood of GHD in pre-pubertal children.
PMID- 17033265
TI - Polycythemia as the first manifestation of Cushing's disease.
AB - A 39-yr-old man presented to our hospital with unexplained erythrocytosis and
hypertension. His follow-up for erythrocytosis had begun 2 yr earlier in another
hospital and he had been diagnosed with polycythemia rubra vera. On admission to
our hospital he was hypertensive (165/95 mmHg) and, except for the presence of
moon-like face and facial plethora, his physical examination was normal. His
hemoglobin concentration was 19.2 g/dl, and hematocrit was 58.9% with an
increased red blood cell mass of 58 ml/kg as measured by radioisotope (Cr51).
Blood film, other hematological indices except for elevated leukocyte alkaline
phosphatase score, arterial gas analysis, and examination of aspirated bone
marrow were all normal. An abdominal ultrasonography showed no evidence of
splenomegaly. A diagnosis of probable secondary erythrocytosis was made. Early
morning serum cortisol and 24-h urinary free cortisol concentration as well as
serum ACTH were high. Serum cortisol was not suppressed by low-dose
dexamethasone, but suppressed by high-dose dexamethasone. Pituitary magnetic
resonance imaging showed no lesion. After inferior petrosal sinus sampling
suggesting right-central ACTH secretion, the patient underwent transnasal
transsphenoidal pituitary adenomectomy. Both hypercortisolemia and erythrocytosis
regressed completely after the adenomectomy. After the operation, the patient's
hemoglobin concentration and hematocrit decreased steadily, and 1 month post
adenomectomy his hemoglobin is 14.9 g/dl and hematocrit 44.8%. Thus, Cushing's
syndrome should be a routine part of evaluation of unexplained polycythemia.
PMID- 17033266
TI - Acromegaly and end-stage renal disease: a diagnostic challenge.
AB - Chronic renal failure is associated with an impairment of the GH/IGF-I axis. We
report the diagnostic challenges in a 72-yr-old female suffering from end-stage
renal disease and presenting with clinical findings suggestive of acromegaly. GH
was not suppressed during an oral glucose tolerance test, but rose paradoxically.
However, serum IGF-I levels were within the normal range. IGF-binding proteins
(IGFBP)-2 and -3 were markedly elevated and GH-binding protein (GHBP) was
diminished. Clinical findings suspicious of acromegaly could be ascribed to pre
existing characteristics and consequences of end-stage renal disease. This
suggested that the disturbances of the GH/IGF-I axis in our patient were due to
chronic renal disease, rather than acromegaly. In the work-up for acromegaly,
clinicians should be alerted to GH resistance in chronic renal failure.
PMID- 17033267
TI - Hyponatremia and pituitary adenoma: think twice about the etiopathogenesis.
AB - Pituitary adenomas may be the cause of the syndrome of inappropriate secretion of
antidiuretic hormone (SIADH), although few cases have so far been reported. We
described a case of hypotonic hyponatremia in a 76-yr-old man with a pituitary
macroadenoma. He had a recent history of two syncopal attacks which had occurred
in the last two months. Baseline assessment demonstrated a sodium serum level of
114 mEq/l. Clinically, the patient appeared euvolemic. Thyroid and adrenal
function testing did not show any abnormality. Plasma and urinary osmolality (238
and 186 mOsm/kg, respectively) were in agreement with the diagnosis of SIADH.
Accordingly, 3% hypertonic saline solution was started, followed by water intake
restriction when natremia reached 126 mEq/l. A computed tomography (CT) scan of
the chest revealed the presence of a 2-cm lesion in the azygos-esophageal recess.
Because the nature of the lesion appeared uncertain, antibiotic therapy was
initiated. After one month, a new CT scan did not show any evidence of the
mediastinic mass. Sodium serum level was within the normal range (141 mEq/l) and
remained stable thereafter, without fluid restriction. This case very well
demonstrates that, in the presence of hyponatremia due to SIADH, more frequently
associated co-morbidities (ie mediastinic diseases) have to be searched, even in
the presence of a possible, yet rare, cause of this syndrome (ie pituitary
adenoma).
PMID- 17033269
TI - The importance of investigation of pituitary function in children and adolescents
following traumatic brain injury.
AB - It is now widely accepted that brain injuries are often the cause of acquired
hypopituitarism in adulthood. The information about the pituitary function in
brain-injured children and adolescence is however scanty. An international
workshop entitled "Traumatic brain injury and hypopituitarism" was held on 9-10
April 2006 in Granada, Spain, in order to explore the relatively unknown but
potentially important field of investigation, diagnosis and treatment of
pituitary deficiency in children and adolescents following traumatic brain injury
(TBI). The following conclusions were reached: 1) a prospective pediatric and
adolescent study of pituitary function was indicated; 2) close collaboration
among neurosurgeons, neurologists, rehabilitation specialists and pediatric
endocrinologists, with support from adult endocrinologists, is essential to
achieve a coordinated approach to the care of children after TBI; 3) a model of
interaction, similar to that now existing with oncologists, needs to be
established; 4) a "pediatric TBI late-effects" service should be created,
preferably led by endocrinologists, so that knowledge of growth and puberty can
be included, in order to optimize identification, investigation and treatment of
this important group of patients.
PMID- 17033268
TI - Diabetic microangiopathy: IGFBP control endothelial cell growth by a common
mechanism in spite of their species specificity and tissue peculiarity.
AB - Endothelial cells (EC) play a role in many diseases including diabetes mellitus.
EC share common functions, such as angiogenesis and vascular remodeling both
regulated by proliferation and apoptosis, anti-thrombotic properties, regulation
of vascular tone, control in the passage of nutrients and secretion of peptides
and growth factors. However, EC are characterized by site-specificity so their
characteristics depend on the organs and tissues where they are. The IGF system
induces important growth factors that control cell growth in different
microvascular EC (mEC). This family includes IGF-I and IGF-II peptides, their
receptors and regulatory proteins IGF-binding proteins (IGFBP-1 to IGFBP-6). The
IGFBP modulate their interaction with the IGF membrane receptors and might be
regulated at a transcriptional and post-transcriptional level, thus determining
the biological IGF-dependent effects on target cells. The IGF system is also a
mediator of vascular diseases, and its altered balance might contribute to
endothelial dysfunction with the development and evolution of diabetic
microangiopathy. We reported here the reviewed literature of IGFBP production
from various sources of mEC, showing that they predominantly express IGFBP-2
through IGFBP-5 mRNA. The different pattern of IGFBP secretion depends on the
anatomical district and on the species of the tissues. Nevertheless, based on our
and other experimental observations, we suggested that a common mechanism of
IGFBP regulation in mEC could be hypothized. In retinal and glomerular EC the
IGFBP4/IGFBP5 ratio controls the response of these cells to IGF-I and high levels
of glucose, in terms of cellular growth.
PMID- 17033270
TI - Assessing the relationship between antigenicity and immunogenicity of human
rabies vaccines. Results of a meta-analysis.
AB - A meta-analysis was done to study the relationship between antigenecity and
immunogenecity of human rabies vaccines. The data of ten cell culture human
rabies vaccine studies conducted at a single centre during 1993-2004 were used in
the study. The vaccines studied included Purified Chick Embryo Cell Vaccine
(Kaketsuken, Japan and Rabipur, India), Purified Vero cell Rabies Vaccine
(Verorab, France), Human Diploid Cell Vaccine (MIRV, France and Rabivax, Adsorbed
and Lyophilized, India) and Rhesus Diploid Rabies Vaccine (adsorbed, USA).
Interestingly, it was revealed that an higher antigenecity of rabies vaccines
viz. potency of > or = 5 IU per single intramuscular dose did not result in
significantly higher immunogenecity, as measured by rabies virus neutralizing
antibody (RVNA) titers in the vaccinees, both on day 14 (t = 0.42, p > 0.66, GMR
= 1.06, 95% CI of GMR = 0.82, 1.37) and day 90 (t = 0.80, p > 0.43, GMR = 1.15,
95% CI of GMR = 0.74, 1.14). However, as there are no reports of meta-analysis of
cell culture human rabies vaccine trials, to confirm this observation the authors
recommend further studies in this regard.
PMID- 17033271
TI - Validation and clinical utility of a simple in-home testing tool for sleep
disordered breathing and arrhythmias in heart failure: results of the Sleep
Events, Arrhythmias, and Respiratory Analysis in Congestive Heart Failure
(SEARCH) study.
AB - Fifty patients with New York Heart Association class III systolic heart failure
were enrolled in this prospective multicenter study that compared the diagnostic
accuracy of a home-based cardiorespiratory testing system with standard attended
polysomnography. Patients underwent at least 2 nights of evaluation and were
scored by blinded observers. At diagnostic cutoff points of > or =5, > or =10,
and > or =15 events per hour for respiratory disturbance severity,
polysomnography demonstrated a sleep-disordered breathing prevalence of 69%, 59%,
and 49%, respectively. Compared with polysomnography, the cardiorespiratory
testing system demonstrated predictive accuracies of 73%, 73%, and 75%, which
improved to 87%, 87%, and 83%, respectively, when analysis of covariance
suggested reanalysis omitting one site's data. The system accurately identified
both suspected and unsuspected arrhythmias. The device was judged by 80% of
patients to be easy or very easy to use, and 74% of patients expressed a
preference for the in-home system. Therefore, this system represents a reasonable
home testing device in these patients.
PMID- 17033272
TI - Brain natriuretic peptide levels and response to cardiac resynchronization
therapy in heart failure patients.
AB - The authors used brain natriuretic peptide (BNP) as a reliable marker to identify
nonresponders to cardiac resynchronization therapy (CRT) in patients with
advanced heart failure. The study included 70 patients with left ventricular
dysfunction (mean ejection fraction, 21+/-4%) and left bundle branch block (QRS
duration, 164+/-25 milliseconds) treated with CRT. The authors reviewed data on
New York Heart Association functional class, baseline ejection fraction, sodium,
creatinine, QRS duration, and BNP levels 3 months before and after CRT therapy.
The authors compared results of 42 patients who survived (973+/-192 days) after
CRT implantation (responders) to those of 28 patients (nonresponders) who either
expired (n=21) or underwent heart transplantation (n=5) or left ventricular
assist device implantation (n=2) after an average of 371+/-220 days. Mean BNP
levels after 3 months of CRT decreased in responders from 758+/-611 pg/mL to
479+/-451 pg/mL (P=.044), while in nonresponders there was increase in BNP levels
from 1191+/-466 pg/mL to 1611+/-1583; P=.046. A rise in BNP levels was associated
with poor response (death or need for transplantation or left ventricular assist
device and impaired long-term outcome), which makes it a good predictor to
identify such patients.
PMID- 17033273
TI - Randomized, double-blind comparison of acute beta1-blockade with 50 mg metoprolol
tartrate vs 25 mg carvedilol in normal subjects.
AB - Differential efficacy of immediate-release metoprolol tartrate and carvedilol in
the treatment of congestive heart failure remains a subject of ongoing debate.
The degree of beta1-blockade can be assessed by percentage reduction of exercise
heart rate. Twelve healthy subjects underwent symptom-limited cardiopulmonary
exercise testing repeated weekly and 2 hours after randomized, double-blind
administration of 50 mg metoprolol tartrate vs 25 mg carvedilol. Baseline heart
rate, heart rate at 40% and 70% peak O2 consumption, and maximal exercise were
significantly blunted more by metoprolol tartrate than by carvedilol (P<.05 for
all). Peak O2 consumption was significantly reduced by metoprolol tartrate
(P<.03) but not by carvedilol (P=.054). The change in O2 consumption was
significantly correlated with the degree of beta1-blockade (r =0.45; P<.05). In
healthy subjects, a higher degree of beta1-blockade is achieved with 50 mg
metoprolol tartrate compared with 25 mg carvedilol.
PMID- 17033274
TI - Prevalence and clinical implications of anemia in congestive heart failure
patients followed at a specialized heart function clinic.
AB - The objective of this study was to assess the prevalence of anemia and to
investigate its association with comorbidities and its impact on clinical
outcomes in patients with heart failure. The association of predefined anemia, as
well as the correlation of serum hemoglobin level as a continuous variable, with
outcomes of emergency department visits, hospitalization, and mortality was
investigated. There were fewer anemic patients in New York Heart Association
classes I and II than in classes III and IV. Anemia was associated with higher
rates of emergency department visits, hospital admissions, and all-cause
mortality. Multivariable analysis showed that anemia is independently associated
with mortality. When hemoglobin level was considered as a continuous variable,
the authors noted that the mortality risk correlated with hemoglobin level
disappears when hemoglobin level exceeds 140 g/L. The authors conclude that
anemia has strong impacts on functional class and other clinical outcomes in
patients with heart failure.
PMID- 17033275
TI - Increase in the QRS duration after amelioration of peripheral edema and after
hemodialysis.
AB - Association among weights, amplitude of QRS complexes, and QRS duration in
patients with peripheral edema has been described. This study explored whether
increase in QRS duration occurs with amelioration of peripheral edema or after
hemodialysis. Sums of the amplitudes of the 12 electrocardiographic leads and
corresponding QRS duration were measured in 12 patients with peripheral edema
before and after loss of weight, in 28 patients with a critical illness but
without change in their weight ("controls"), and in 1 patient before and after
hemodialysis. QRS duration increased from 90.1+/-25.0 milliseconds to 101.7+/
25.8 milliseconds (P=.001) in patients with peripheral edema, was unchanged in
the controls, and increased from 87.8+/-5.9 milliseconds before to 92.7+/-6.7
milliseconds after hemodialysis (P=.007). It is proposed that these increases in
QRS duration are only apparent (not electrophysiologically real), representing an
extracardiac phenomenon mediated by alterations in the composite impedance of the
passive body volume conductor, resulting in measurement of augmented QRS
complexes after fluid removal. The clinical implications for patients with
congestive heart failure are discussed.
PMID- 17033276
TI - Improving the accuracy of impedance cardiac output in the intensive care unit:
comparison with thermodilution cardiac output.
AB - This study examined the effect of impedance algorithm adjustment to reflect
abnormalities found in cardiac output estimation in the intensive care unit.
Impedance (Kubicek and Sramek equations) and thermodilution were measured
concurrently in 61 patients. The mean difference between Kubicek and
thermodilution (n=40) was 1.47 L/min (95% confidence interval [CI], 0.47-2.47)
and between Sramek and thermodilution (n=54) was 2.68 L/min (95% CI, 1.93-3.44).
Exclusion of patients with valve regurgitation improved agreement between Kubicek
and thermodilution (n=32), with a mean difference of 2.02 L/min (95% CI, 1.10
2.94). Multiple regression determined the role of skinfold thickness, pH,
hematocrit, sodium, chloride, albumin, protein, and urea within impedance.
Kubicek was recalculated using the new algorithm and recompared with
thermodilution. The mean difference was -0.38 L/min (95% CI, -1.92 to 1.16). This
study found poor agreement between impedance and thermodilution in critically ill
patients, but exclusion of those with valve regurgitation and adjustment for
hematocrit and skinfold thickness improved agreement.
PMID- 17033277
TI - ECG changes in response to diuresis in an ambulatory patient with congestive
heart failure.
AB - This case report describes an ambulatory patient with congestive heart failure
and peripheral edema who lost 18 lb in response to enhanced diuresis over the
course of 1 week. The ECG showed increases in the amplitude of P waves, QRS
complexes, and T waves; the duration of P waves, QRS complexes, and QT intervals;
and the dispersion of P and QT. The clinical implications of these ECG changes
are discussed.
PMID- 17033278
TI - History of heart failure.
PMID- 17033281
TI - New advances in the molecular and cellular biology of the small intestine.
AB - Research into the structure and function of the small intestinal mucosa is
becoming increasingly focused on the molecular and cellular biology of this
fascinating tissue. There is a growing understanding of the factors determining
the expression of specific genes at different stages of development and
differentiation in the multiple cell types, and several important transcription
factors have emerged. Recent publications have included studies of the effects of
commensal bacteria on gene expression and the molecules producing apoptosis.
Mechanisms of the intestinal adaptation to injury or surgery involve a number of
hormones; current research has shown a major role for glucagon-like peptide 2.
PMID- 17033282
TI - Nutrient absorption.
AB - Many advances in the study of nutrient absorption have been made with the use of
molecular and genetic techniques; however, standard in vivo studies have provided
interesting and important new information. Omega-3 long-chain fatty acids have
unexpected effects on lipoprotein formation and secretion in neonatal intestinal
cells; this needs to be considered in the modification of infant formulas.
Rexinoids affect intestinal cholesterol homeostasis via two receptors: retinoic
acid receptor/liver X receptor (cholesterol efflux to lumen) and retinoic acid
receptor/farnesoid X receptor (cholesterol catabolism). Absorption of the
antioxidant plant polyphenol quercetin involves interaction with the glucose
transporter and deglycolsylation and conjugation reactions. Cells of the
polarized human colon cancer cell line, CaCo-2, take up phenylalanine by two
mechanisms: passive uptake across the basolateral membrane, and temperature
dependent transcellular movement from apical to basolateral media. Absorption of
vitamins A and E is markedly enhanced in normal and damaged intestine by the
administration of restructured triacylglycerols derived from fish oil and medium
chain fatty acids. Surprisingly, dietary protein and phosphorus apparently have
no significant effect on the efficiency of calcium absorption in adult women.
Finally, many studies examined a variety of genes that regulate iron absorption
and homeostasis.
PMID- 17033283
TI - Fluid and electrolyte transport in the small intestine.
AB - The small intestine is in a dynamic state of secretion and absorption, the sum of
which results in net absorption. Secretion is principally the result of chloride
and bicarbonate extrusion through apical chloride channels after the activation
of the second messengers cAMP, cGMP, and calcium. In addition to the cystic
fibrosis transmembrane conductance regulator, several other candidate chloride
channels have been identified and proposed to play a role in intestinal
secretion, including the calcium-dependent chloride channel hCLCA1. Pathways
leading to the negative control of secretion have been described that use
cellular messengers, including inositol (3,4,5,6) tetrakisphosphate and
phosphatidylinositol 3-kinase, which may act via basolateral potassium channels.
The control of ion transport can also be viewed in terms of the enteric nervous
system. The reflex neural pathways involved in enterotoxin-induced secretion have
been substantiated and shown to involve 5-hydroxytryptamine, substance P, and the
neurokinin 1 and 2 receptors in the sensory arm, and vasoactive intestinal
peptide in the secretomotor efferents. Absorption of glucose in addition to
active cotransport with sodium via the Na/glucose cotransporter protein has also
been shown to occur passively through a carrier-mediated mechanism, using the
membrane protein glucose transporter protein 2.
PMID- 17033284
TI - Recent developments in celiac disease.
AB - Celiac disease is a common disorder associated with a substantially increased
standardized mortality ratio if it is left untreated or if the diagnosis is
delayed. Diagnostic sensitivity of serologic testing is improved by the addition
of IgG-based testing to standard IgA-based serologic testing for endomysial or
transglutaminase autoantibodies. The role of intestinal permeability testing as
an additional tool for screening and for monitoring the response to a gluten-free
diet is discussed. The importance of diagnosing celiac disease in two clinical
situations is considered: first, before immune-stimulating therapy with
interferon for viral hepatitis is begun and second, in pregnancy when not only
maternal but also paternal celiac disease may affect fetal outcome. The strong
genetic component of the etiology of celiac disease is illustrated by a
monozygotic twin concordance of nearly 90%, with susceptibility conveyed by human
leukocyte antigen (HLA) genotypes DQ2 or DQ8 and one or more non-HLA genes.
Progress toward identifying these genes from large linkage and association
studies is reviewed.
PMID- 17033285
TI - Small bowel motility.
AB - The publications relevant to small bowel motility have been concentrated during
the past year in several main areas: further characterization of normal patterns
of small bowel motor activity and transit, physiologic control mechanisms,
visceral hypersensitivity, inflammation and motility, disease processes and
dysmotility, and novel pharmacologic approaches to altered sensorimotor activity.
PMID- 17033286
TI - Surgery of the small intestine.
AB - The small intestine is the portal of entry of virtually all nutrients and is also
the site of diverse inflammatory and neoplastic diseases. This field has recently
attracted intense excitement as a result of novel clinical and experimental
techniques, combined modality therapies, and basic science applications. This
review will highlight important clinical advances in surgery for Crohn disease,
short bowel syndrome, transplantation, trauma, and polyposis. Promising
experimental approaches, novel methods of clinical assessment, and multimodality
treatment will also be considered.
PMID- 17033287
TI - Small bowel infections.
AB - Infections of the human gastrointestinal tract with enteric pathogens are among
the leading causes of disease, suffering, and death worldwide. Enteric pathogens
are ingested from contaminated food and water and pass through the entire
gastrointestinal tract during establishment in the host and subsequent shedding
and spread to new hosts. Nonetheless, each pathogen exploits a unique niche
within the intestinal tract and has developed unique strategies to interact with
different host cells and functions. The most important and prevalent infections
of the small intestine are caused by diarrheagenic Escherichia coli, particularly
enterotoxigenic and enteropathogenic E. coli, rotavirus, Giardia lamblia, and
Cryptosporidium parvum. This review focuses on recent insights into the
pathogenesis of infections with these pathogens and host defenses against them.
PMID- 17033288
TI - The role of nutritional deficiency in the osteopenia and osteoporosis of
gastrointestinal diseases.
PMID- 17033289
TI - Enteral feeding.
AB - In this review, topics with scientific strength, topical interest, and
controversy were selected. Over the past 50 years, malnutrition has become
increasingly recognized as a cause of increased morbidity and mortality in
hospital patients. From 1970 to 1980, parenteral nutrition was advocated as the
most appropriate form of nutritional therapy for hospital patients. Since then,
parenteral nutrition has been replaced by enteral nutrition as the best way of
delivering nutrients to hospital patients. The timing of enteral nutrition has
been debated. Should it be instituted early, within the first 24 hours? In
addition, enteral nutrition containing immune-enhancing nutrients such as
arginine, omega-3 fatty acids, glutamine, and nucleotides has been advocated for
critically ill patients. The relative merits of enteral versus total parenteral
nutrition continue to be debated. Questions about possible complications related
to enteral nutrition have been raised. Patients are at risk of nosocomial
pneumonia from aspiration and at risk of bowel ischemia because enteral nutrition
increases intestinal oxygen consumption. Steroids are often used to treat Crohn
disease, but because of undesirable side effects, various techniques have been
used to reduce steroid dependency. Enteral nutrition has been advocated as a way
of reducing steroid dependency. Finally, enteral nutrition is routinely used to
feed demented patients and those in a vegetative state. It is not clear whether
this practice alters outcome or quality of life.
PMID- 17033290
TI - Obesity pharmacology: past, present, and future.
AB - Over the past several years, the pharmacologic treatment of obesity has undergone
changes in safety, efficacy, and therapeutic targeting. The prevalence of cardiac
valvulopathy associated with treatment with phentermine, fenfluramine, and
dexfenfluramine is now becoming clarified with the publication of longer-term
studies. Phenylpropanolamine, a well-known over-the-counter appetite suppressant,
was recently removed from the market in the United States because of an increased
risk of hemorrhagic stroke in women. In contrast, two currently approved
medications, sibutramine and orlistat, have been shown to be safe and moderately
effective for weight loss with documented beneficial effects on cardiovascular
risk factors. Three other drugs, bupropion, topiramate, and ciliary neurotrophic
factor, are undergoing clinical trials for obesity based on empirical
observations. Most promising are the advances in genetics and molecular biology
that are beginning to elucidate new targets for controlling appetite and energy
utilization. These therapeutic agents will likely herald a second generation of
anti-obesity medications over the next decade.
PMID- 17033291
TI - Malnutrition and gastrointestinal disease.
AB - The recognition of several disease processes that cause or are associated with
gastrointestinal malabsorption has led to extensive investigation into their
pathogenesis, diagnosis, and treatment. This review of selected articles covers a
range of subjects related to some of the more common malabsorptive disease.
Selected topics including celiac disease, disaccharidase deficiencies, short
bowel syndrome, and Crohn disease are discussed.
PMID- 17033292
TI - Diet, folate, and colon cancer.
AB - Evidence emerging from many different types of experimental designs continues to
support the concept that dietary habits and nutritional status play important
roles in determining the risk of colorectal cancer. This field of investigation
is nevertheless very confusing, particularly because longstanding hypotheses,
such as the presumed protective effects of fruits, vegetables, and fiber, have
recently been challenged by well-designed prospective trials. The search for
individual components in the diet that convey protection continues: calcium,
folate, selenium, and omega-3 fatty acids are the leading candidates in this
regard. There is also growing interest in other plant-based compounds, so-called
phytochemicals, although our understanding of their effects is quite rudimentary
at present. Although the inconsistencies in this field make it tempting to
minimize its import, there is little question that diet has a major impact on
colorectal cancer risk; diligent attention to the rigorous conduct of studies and
their interpretation will likely clarify these relationships over the next
decade, much to the benefit of public health.
PMID- 17033293
TI - Probiotics in gastroenterology.
AB - Recent evidence has suggested the potential therapeutic role for probiotics in
the prevention or treatment of gastrointestinal diseases. Several studies have
shown that probiotics are of benefit in gastrointestinal infections, including
viral diarrhea, Clostridium difficile-associated diarrhea, traveler's diarrhea,
and antibiotic-associated diarrhea. Recent data support the potential beneficial
therapeutic effect in inflammatory bowel disease as well. Other possible
indications for probiotic treatment include Helicobacter pylori infection,
irritable bowel syndrome, and radiotherapy-associated diarrhea. It is important
to select well-characterized preparations; in fact, the viability and survival of
many available preparations are unproven. More precise information on the
mechanisms by which probiotic strains exert their beneficial effects in vivo is
needed. This may provide the scientific rationale for the selection of the best
probiotic strains to use in the performance of large, double-blind, controlled
clinical trials.
PMID- 17033294
TI - Nutrition in the elderly.
AB - It is now well accepted that older persons experience a physiologic anorexia, the
anorexia of aging, which is caused by alterations in hedonic qualities of food,
fundal compliance, and increased leptin levels. Depression is the most common
pathologic cause of weight loss in older persons. Older persons fail to recognize
thirst and as such have an increased risk of dehydration. Alterations in brain
membrane fatty acids can lead to cognitive impairment in older persons.
PMID- 17033295
TI - Current nutrition in liver disease.
AB - Malnutrition is common in severe liver disease. Assessment of malnutrition
usually requires a subjective global assessment of the patient with a few
additional tests that often include handgrip strength and arm-muscle
circumference. The severity of liver disease correlates well with the severity of
malnutrition, which has prognostic value. Malnutrition is multifactorial, is
difficult to correct, and occurs in liver disease independently of the etiology
of hepatic injury. Patients who have severe protein-calorie malnutrition require
diets with high calorie and protein intake, even in the presence of hepatic
encephalopathy. Some forms of complementary and alternative medicine are
frequently used in patients with advanced liver disease, but supporting
scientific data is needed. Obesity is detrimental to patients with advanced liver
disease and is of greater concern in liver transplant candidates because it
increases transplant-related morbidity. Data detailing the effects of aggressive
nutritional support before transplantation are scarce, and more studies are
needed.
PMID- 17033297
TI - Bibliography current world literature.
PMID- 17033296
TI - Cholesterol absorption.
AB - Cholesterol absorption is a key regulatory point in human lipid metabolism
because it determines the amount of endogenous biliary as well as dietary
cholesterol that is retained, thereby influencing whole body cholesterol balance.
Plant sterols (phytosterols) and the drug ezetimibe reduce cholesterol absorption
and low-density lipoprotein cholesterol in clinical trials, complementing the
statin drugs, which inhibit cholesterol biosynthesis. The mechanism of
cholesterol absorption is not completely known but involves the genes ABC1,
ABCG5, and ABCG8, which are members of the ATP-binding cassette protein family
and appear to remove unwanted cholesterol and phytosterols from the enterocyte.
ABC1 is upregulated by the liver X (LXR) and retinoid X (RXR) nuclear receptors.
Acylcholesterol acytransferase-2 is an intestinal enzyme that esterifies absorbed
cholesterol and increases cholesterol absorption when dietary intake is high. New
clinical treatments based on better understanding of absorption physiology are
likely to substantially improve clinical cholesterol management in the future.
PMID- 17033299
TI - Hepatobiliary pathology.
AB - Technologic advances using cDNA microarray hybridization, liver diseases
characterized by mitochondrial DNA depletion, and new work characterizing bile
salt transport problems in familial intrahepatic cholestasis syndromes were some
of the major highlights of this past year. Analysis of normal livers by cDNA
microarrays disclosed 2418 unique gene transcripts encoding a host of cellular
structural and functional proteins. This technique was also applied to
hepatocellular carcinoma, where enhanced expression of a number of genes involved
in antiapoptosis and cell transformation may shed additional light on the process
of hepatocarcinogenesis. Mitochondrial DNA depletion seen in Navajo
neurohepatopathy and in respiratory chain disorders of infancy was associated
with cholestasis and cirrhosis in the former and microvesicular steatosis and
oncocytic transformation (mitochondrial hyperplasia) in the latter. Pathologists
who routinely examine liver biopsies after liver or bone marrow transplantation
should be aware of unusual biopsy features that mimic other diseases, such as the
autoimmune hepatitis-like syndrome that may follow liver transplantation and
chronic graft-versus-host disease that clinically and pathologically resembles
acute hepatitis.
PMID- 17033300
TI - Inherited metabolic disease.
AB - The elucidation of metabolic pathways and the genetic basis for diseases of the
liver continues to increase our understanding of disease pathogenesis and advance
treatment options. This selective review covers a wide range of subjects, from
the identification of novel proteins and the importance of specific transport
pathways to phenotypic expression of disease and management of acute liver
failure. Three selected disorders--Wilson disease, genetic hemochromatosis and
other hereditary iron overload disorders, and alpha(1)-antitrypsin disease--are
the focus of this review.
PMID- 17033301
TI - Drug-induced liver disease.
AB - Although the year 2001 did not see any prescription drugs withdrawn because of
drug-induced liver disease, the US Food and Drug Administration requested that
dietary supplements containing comfrey be taken off the market because of the
danger of hepatic injury. The Food and Drug Administration remains very involved
in the process by which drug-induced liver disease can be detected early in drug
development and in the determination of how best to prevent hepatotoxicity after
drug approval. A workshop on drug-induced liver disease cosponsored by the Food
and Drug Administration, the Pharmaceutical Research and Manufacturers
Association, and the American Association for the Study of Liver Diseases was
held in Washington, DC, in February 2001, and the resulting white paper outlined
several areas for research. A number of agents were newly described as causing
various forms of liver injury, and several others had drug-induced liver disease
confirmed by additional reports. Several investigators dealt with the
difficulties inherent in establishing causality of drug-induced liver disease and
the potential negative consequences of wrongly attributing hepatotoxicity to a
particular agent. In one recent series, more than half the instances of alleged
drug-induced liver disease were found to have other causes, often leading to a
delay in the actual diagnosis and appropriate management. Case reports in
particular were often misleading. Although several drug assessment scales have
been developed, none appears to be foolproof.
PMID- 17033302
TI - Cholestatic syndromes.
AB - Further insights into the molecular regulation of bile acid transport and
metabolism have provided the basis for a better understanding of the pathogenesis
of cholestatic liver diseases. Novel insights into the mechanisms of action of
ursodeoxycholic acid should advance our understanding of the treatment of
cholestatic liver diseases. Mutations of transporter genes can cause hereditary
cholestatic syndromes in both infants and adults as well as cholesterol gallstone
disease. Important studies have been published on the pathogenesis, clinical
features, and treatment of primary biliary cirrhosis, drug-induced cholestasis,
and cholestasis of pregnancy.
PMID- 17033303
TI - Viral hepatitis.
AB - Viral hepatitis affects millions of people worldwide, making it one of the most
important diseases in the field of hepatology. The response to the hepatitis A
vaccine is optimal when targeted to patients with chronic hepatitis before
development of hepatic decompensation. A new triple antigen vaccine for hepatitis
B virus produces a greater degree of protection. Lamivudine can achieve a 3-to 4
log reduction in serum viral levels in patients with chronic hepatitis B
infection. Lamivudine-resistant mutants appear in more than 50% of patients after
prolonged treatment. Entecavir can be given safely for a short time and causes a
pronounced reduction in hepatitis B viral DNA levels with slower rebound after
stopping therapy than has been reported with lamivudine. Pegylated interferon has
sustained absorption, a slower rate of clearance and a longer half-life than
unmodified interferon alfa. Pegylated interferon alfa-2a administered once weekly
is more effective than standard interferon alfa-2a administered three times
weekly. In patients with chronic hepatitis C infection, the most effective
therapy is the combination of pegylated interferon plus ribavirin. Other major
advances in the field of viral hepatitis during the past year are highlighted.
PMID- 17033304
TI - Autoimmune liver disease.
AB - Autoimmune hepatitis is as virulent in the elderly as in the young, and initial
treatment should be similar. Antiphospholipid antibodies should be sought in all
patients with a history of fetal loss or arterial or venous thrombosis. The C282Y
mutation in the HFE hemochromatosis gene occurs more commonly in autoimmune
hepatitis than in normal subjects, but it is not associated with distinctive
features. Children with autoimmune hepatitis may have abnormal cholangiogram
results, but the syndrome of autoimmune sclerosing cholangitis does not affect
immediate prognosis. Bile duct changes, including destructive cholangitis, can be
incidental findings that have no clinical expression or therapeutic consequence.
In South America, DRB1*1301 is associated with protracted hepatitis A virus
infection which may enhance exposure to hepatic self-antigens in children.
Interferon gamma-inducible protein 10 may be an important chemokine that promotes
liver damage by attracting activated T cells. Transcripts of Fas ligand are
abnormally increased in autoimmune hepatitis, and apoptotic dysfunction may
contribute to disease progression. Pregnancy is not contraindicated in autoimmune
hepatitis, and cyclosporine may be effective as first-line therapy.
PMID- 17033305
TI - Hepatocellular carcinoma.
AB - The number of papers published regarding hepatocellular carcinoma increased
remarkably over the previous year. The 1-year survival for hepatocellular
carcinoma has only improved slightly over the past 20 years, while the overall
survival has remained unchanged. Hepatitis B genotypes, specifically genotype B,
correlate with better response and survival in patients with hepatocellular
carcinoma caused by this chronic infection. A consensus conference recommended
that patients with Child-Turcotte-Pugh class A or B cirrhosis should be screened
with ultrasound and alpha-fetoprotein measurement every 6 months. Using
microarray technology, several groups established the gene expression for human
hepatocellular carcinoma including the identification of potential genes involved
in hepatic carcinogenesis. Dynamic gadolinium MRI is the preferred imaging of
choice for the evaluation of hepatocellular carcinoma, but contrast-enhanced
power Doppler ultrasound is a new imaging technique able to differentiate
neoplastic from nonneoplastic liver lesions. Overall, transplantation is the best
long-term therapeutic option, but in patients without portal hypertension and
well-preserved liver function, resection may be preferable.
PMID- 17033306
TI - Portal hypertension.
AB - Portal hypertension is the main complication of cirrhosis and is responsible for
its most common complications: variceal hemorrhage, ascites, and portosystemic
encephalopathy. Portal hypertension is the result of increased intrahepatic
resistance and increased portal venous inflow. Vasodilatation (splanchnic and
systemic) and the hyperdynamic circulation are hemodynamic abnormalities typical
of cirrhosis and portal hypertension. Gastroesophageal varices result almost
solely from portal hypertension, although the hyperdynamic circulation
contributes to variceal growth and hemorrhage. Ascites results from sinusoidal
hypertension and sodium retention, which is in turn secondary to vasodilatation
and activation of neurohumoral systems. Hepatic hydrothorax results from the
passage of ascites across the diaphragm and into the pleural space. The
hepatorenal syndrome represents the result of extreme vasodilatation with an
extreme decrease in effective blood volume that leads to maximal activation of
vasoconstrictive systems, renal vasoconstriction, and renal failure. Spontaneous
bacterial peritonitis is a potentially lethal infection of ascites that occurs in
the absence of a local source of infection. Portosystemic encephalopathy is a
consequence of both portal hypertension (shunting of blood through portosystemic
collaterals) and hepatic insufficiency resulting in the accumulation of
neurotoxins in the brain.
PMID- 17033307
TI - Cholangiocyte biology.
AB - Due in part to the recent development of new experimental models, cholangiocytes-
the epithelial cells that line the bile ducts--are increasingly recognized as
important transporting epithelia actively involved in the absorption and
secretion of water, ions, and solutes. New biologic concepts have emerged
including the identification and topography of receptors and flux proteins
involved in the molecular mechanisms of ductal bile secretion. Individually
isolated or perfused bile duct units from livers of rats and mice serve as new,
physiologically relevant in vitro models to study cholangiocyte transport.
Biliary tree dimensions and novel insights into anatomic remodeling of
proliferating bile ducts have emerged from three-dimensional reconstruction using
computed tomographic scanning and sophisticated software. Moreover, new
pathologic concepts have arisen regarding the interaction of cholangiocytes with
pathogens. These concepts may provide the framework for new therapies for the
cholangiopathies, a group of important hepatobiliary diseases in which
cholangiocytes are the target cell.
PMID- 17033308
TI - Cholesterol gallstones.
AB - Cholesterol cholelithiasis is common in Western populations and represents a
consequence of altered cholesterol homeostasis. Gallstones form because of a
complex and incompletely understood series of metabolic and physicochemical
events that promote cholesterol crystallization in bile. In the context of
current paradigms, this article reviews recent progress in research on biliary
lipid metabolism and the pathogenesis of cholesterol gallstones.
PMID- 17033309
TI - Sclerosing cholangitis.
AB - Primary sclerosing cholangitis in children can mimic autoimmune hepatitis in the
absence of inflammatory bowel disease. Most adult patients have been identified
with human leukocyte antigens that either predispose or protect against disease.
Novel class I alleles and cytokine polymorphisms may also contribute to disease
susceptibility. Primary alpha-hemolytic streptococci infection does not appear to
directly cause primary sclerosing cholangitis. Promising diagnostic modalities
such as single photon emission tomography require further study in comparison
with cholangiographic techniques. Positron-emission tomography and DNA cytometry
appear promising for confirming occult cholangiocarcinoma when present. The
chemoprevention effects of ursodeoxycholic acid on colorectal dysplasia await
further investigation. Initial results from high-dose ursodeoxycholic acid in
halting disease progression, however, suggest a beneficial effect. In contrast,
the impact of endoscopic therapy on natural history remains unresolved. Although
liver transplantation continues to be effective for end-stage liver disease,
disease recurrence in the allograft is a controversial topic.
PMID- 17033310
TI - Endoscopic management of biliary disease.
AB - Therapeutic biliary endoscopy continues to evolve. Key articles this year
primarily involve biliary stenting and biliary stone removal, the two important
maneuvers available to the biliary endoscopist. The issues addressed in this
review include follow-up after the use of multiple stents for benign strictures,
unilateral versus bilateral stenting for Klatskin tumors, stent types and
placement positions, the timing and approach to choledocholithiasis in the
context of anticipated cholecystectomy, and resistant biliary duct stones.
PMID- 17033311
TI - Bibliography current world literature.
PMID- 17033312
TI - Professor Dame Sheila Sherlock (1918-2001).
PMID- 17033313
TI - Inflammatory bowel disease: genetics and much more.
PMID- 17033314
TI - Update on genetics of inflammatory bowel disease.
AB - Complex genetic disorders such as inflammatory bowel disease (IBD) result from
the interplay between multiple genetic and environmental risk factors. The recent
identification of variants of the CARD15/NOD2 protein as contributing to Crohn
disease represents a major advance in defining disease pathogenesis. CARD15/NOD2
is expressed in monocytes and is capable of activating nuclear factor kappa B (NF
kappaB). Crohn disease-associated mutations in CARD15/NOD2 predominate in its C
terminus leucine-rich repeat domain, which is required for bacterial
lipopolysaccharide-dependent induction of NF-kappaB activity. The relative risk
of developing Crohn disease is estimated to be in the range of 2 to 3 in people
carrying one mutation and 20 to 40 in people carrying two mutations in
CARD15/NOD2. Homozygote and compound heterozygote carriers of CARD15/NOD2
mutations are characterized by an earlier age of onset, less involvement of the
left colon, and positive association with stricturing disease. However, even
carriers of two CARD15/NOD2 mutations have limited disease penetrance (ie, only a
minority will develop the disease), suggesting that additional interacting genes
and environmental triggers are required for disease expression. Several
additional genetic regions have been implicated through genetic linkage and
association studies.
PMID- 17033315
TI - Epidemiology of inflammatory bowel disease.
AB - Despite the apparent continuous increase of the incidence of inflammatory bowel
disease (IBD) in some populations, or some sections of populations such as
British children, the origin of these conditions remains obscure. Epidemiological
studies of specific risk factors continue to yield contradictory and inconclusive
results. However, studies of exposure and comorbidity, coupled with genetic and
molecular studies, expand our knowledge and will facilitate more sophisticated
research in the near future. Our understanding of the genetic basis of IBD is
improving, but genetic anticipation as an explanation for increasing incidence
rates appears less probable. The benefit of giving up smoking has been
demonstrated in Crohn's disease patients, because smoking influences disease
activity. The increased cancer risk in IBD is a concern, but despite this, the
overall mortality in IBD is no higher than that of the general population.
PMID- 17033316
TI - Immunopathogenesis of inflammatory bowel disease.
AB - Inflammatory bowel disease (IBD) is characterized by inflammation that results
from the interaction between the various components of the mucosal immune system
and the microenvironment. These components-lu}inal antigens, intestinal
epithelial cells (IEC), lymphocytes, and cells of the innate and adaptive immune
system and their secreted mediators (cytokines and chemokines)-contribute to the
cascade of events that ends in intestinal and systemic damage in a genetically
predisposed host. The origin of IBD is as yet unknown, but the beginning of the
third millennium has brought several new insights into the immune aberrations in
IBD. The progress achieved last year in each component of IBD pathogenesis will
be reviewed. In each section, an attempt to develop correlations between
experimental findings and human disease is made.
PMID- 17033317
TI - Osteoporosis and other complications of inflammatory bowel disease.
AB - Osteoporosis has received increasing attention as a potential complication of
inflammatory bowel disease (IBD). The first population-based data on incidence of
fractures in an IBD population were published this past year. The incidence of
fractures was one per 100 patient years. Compared with the general population,
the fracture rate was increased; however, the relative risk was 1.4 and,
therefore, not as high as might be expected from the myriad of studies reporting
high rates of osteopenia measured by dual energy x-ray absorptiometry (DXA).
Another area receiving increasing attention is that of the enhanced risk of
venous thrombosis in patients with IBD. The first population-based incidence
rates of venous thrombosis in IBD were also published this past year and showed
that IBD patients are affected by venous thrombosis at a rate of approximately
one per 200 patient years. The relative risk for venous thrombosis compared with
the general population was 3.5. Several studies have reported on associated risk
markers or genetic clotting abnormalities, but no clear paradigm has emerged to
account for those patients who will suffer a clot. Finally, the first North
American population-based study was published, quantifying the prevalence rates
of extraintestinal manifestations in patients with IBD for at least 10 years.
Some gender- and disease-specific findings emerged. This study found that iritis
and uveitis were more common in female patients with ulcerative colitis (3.2%),
primary sclerosing cholangitis (PSC) was most common in male patients with
ulcerative colitis (3%), ankylosing spondylitis was most common in male patients
with Crohn disease (2.7%), and erythema nodosum was most likely to occur in
female patients with Crohn disease (1.9%).
PMID- 17033318
TI - Advances in the medical therapy of inflammatory bowel disease.
AB - The medical therapy of inflammatory bowel disease (IBD) has advanced
significantly over the past year. Serologic markers of IBD have been further
investigated and better defined, showing some discriminatory power with potential
therapeutic implications. Studies of azathioprine and 6-mercaptopurine
metabolites will make it easier and safer to use these effective drugs. Clinical
data using other immunomodulators, including 6-thioguanine, mycophenolate
mofetil, cyclosporine, and tacrolimus, continue to accrue with positive results.
Infliximab has become even more firmly established as a reliable and effective
therapy for active and fistulizing Crohn disease and may even be helpful in some
patients with resistant ulcerative colitis. However, the recognition of potential
complications of infliximab therapy has increased with the accumulated clinical
experience. Results from trials of other biologic therapies directed at tumor
necrosis factor alpha have been disappointing so far, although preliminary
studies with biologics directed at adhesion molecules are encouraging. Growing
appreciation of the importance of the enteric microflora in IBD has led to a
considerable interest in manipulating intestinal bacteria for therapeutic
benefit, and trials of both probiotics and prebiotics show promise.
PMID- 17033319
TI - Surgical treatment of inflammatory bowel disease.
AB - Appropriate surgical management of Crohn disease is predicated on multiple
variables, but stricturoplasty is generally reserved for small bowel disease,
whereas resection is utilized in ileocolonic inflammation and favored for large
bowel disease. Laparoscopic resection is becoming increasingly useful and
justified for ileocolic resections, and segmental resection should be strongly
considered for limited large bowel inflammation. Some centers are also using a
laparoscopic approach for the surgical treatment of acute or chronic ulcerative
colitis, although the benefits are less apparent. Proctocolectomy with ileostomy
or ileal pouch-anal anastomosis returns the patient's quality of life to a level
comparable to that enjoyed by the general population. Creation of a pouch is
performed in most instances, but early complications may warrant pouch revision
and later complications, such as pouchitis, can mandate pouch excision.
PMID- 17033320
TI - Gastroesophageal reflux disease.
AB - Gastroesophageal reflux disease (GERD) affects many patients and has a negative
effect on quality of life. Along with the increasing prevalence of GERD is an
increase in GERD-related complications, including Barrett esophagus and
esophageal adenocarcinoma. The past year has yielded new insights into the
pathophysiology of GERD that can help us to better understand the relationship
between reflux episodes and symptoms of mucosal damage and to provide a tailored
treatment targeting individual pathophysiologic defects. The issues addressed in
this report include gastric secretory and motor dysfunction; failure of the
antireflux barrier caused by hiatal hernia and transient lower esophageal
sphincter relaxations; characterization of the refluxate, particularly of nonacid
reflux; prevalence and prognostic value of esophageal dysmotility in GERD;
presence and eradication of Helicobacter pylori; Barrett esophagus and
extraesophageal manifestations of GERD; and, finally, advances in medical,
endoscopic, and surgical treatments of GERD.
PMID- 17033321
TI - Esophageal motor disorders.
AB - Refinements continue in the measurement, display, and interpretation of pressure
events that serve as signatures of esophageal motor disorders, and esophageal
manometry retains its position as the diagnostic gold standard. The focus of
attention remains with achalasia, not because of pathophysiologic developments or
changing prevalence, but in response to the growing interest in minimally
invasive surgery and its success. Some controversy remains regarding the role of
preoperative motility assessments in patients undergoing antireflux surgery, as
peristaltic features do not solely predict outcome. The disconnect between motor
dysfunction and symptoms continues to promote careful consideration of sensory
dysfunction as a component of esophageal motor disorders.
PMID- 17033322
TI - Chest pain of esophageal origin.
AB - Chest pain of esophageal origin is the most common atypical/extraesophageal
manifestation of gastroesophageal reflux disease (GERD). We are increasingly
recognizing the important role of the cardiologist in making the diagnosis.
Studies continue to focus on the mechanisms of pain in this challenging group of
patients. Factors that determine the development and persistence of visceral
hypersensitivity are currently under investigation. Invasive diagnostic studies
have been replaced by therapeutic trials or empirical therapies. Proton pump
inhibitors have been demonstrated to be the most effective treatment for GERD
related noncardiac chest pain (NCCP). Pain modulators remain the primary therapy
for non-GERD-related NCCP. Sertraline is the first selective serotonin reuptake
inhibitor to demonstrate a significant improvement in chest pain symptoms.
PMID- 17033323
TI - Barrett esophagus.
AB - A number of publications have provided valuable insight into and data on the
epidemiology, pathogenesis, diagnosis, risk factor evaluation, and treatment of
patients with Barrett esophagus. Although the incidence of esophageal
adenocarcinoma has rapidly increased over the past two decades, it is not clear
whether there has been a parallel increase in the frequency of Barrett esophagus.
The issue of surveillance endoscopy in patients with Barrett esophagus remains
controversial; prospective data are still lacking. Bile reflux plays an important
role in the pathogenesis of Barrett esophagus; however, this usually occurs in
the presence of acid. Newer technology and techniques, including chromoendoscopy,
magnification endoscopy, optical coherence tomography, and spectroscopy, have
opened the field by providing a more accurate and "nonbiopsy" diagnosis of
intestinal metaplasia and dysplasia. The field of biomarkers remains continues to
expand and is providing insight into risk stratification of patients with Barrett
esophagus. The exact role of acid suppression in patients with this premalignant
disease remains controversial, and endoscopic therapies appear promising.
PMID- 17033324
TI - Endoscopic therapeutic esophageal interventions.
AB - In Western countries, many esophageal diseases result from uncontrolled
gastroesophageal reflux. Treatments for Barrett esophagus, peptic strictures, and
esophageal adenocarcinoma still account for a large portion of the esophageal
interventions performed by therapeutic endoscopists. In addition to continued
refinements in the treatment of these sequelae, new endoscopic therapies have
emerged to treat gastroesophageal reflux disease itself. This article reviews the
available literature on new endoscopic antireflux procedures along with other
advances that give the endoscopist unprecedented options in the treatment of
esophageal diseases.
PMID- 17033325
TI - Esophageal cancer.
AB - Despite advances in our knowledge of esophageal cancer, 50% of patients present
with incurable disease, and the overall survival after diagnosis is poor. The
incidence of esophageal adenocarcinoma of the distal esophagus is rising at a
rapid rate in developed countries. Recent advances in the epidemiology of
esophageal cancer offer insights into preventive strategies in patients who are
at risk. New developments in diagnosis may help detect the disease at an early
stage. New diagnostic modalities permit more accurate staging procedures and
allow appropriate selection of therapy. New studies provide more information on
multimodality therapy for esophageal cancer, and new endoscopic techniques allow
resection of small lesions without surgery. New stent designs provide better
palliation by providing tumor ingrowth. These developments in the treatment of
esophageal cancer are the focus of this review.
PMID- 17033327
TI - Bibliography current world literature. Inflammatory bowel disease.
PMID- 17033326
TI - Esophageal carcinoma: surgery, radiotherapy, and chemotherapy.
AB - Several new developments in the potentially curative therapy of esophageal cancer
have drawn attention over the past year. There is a potential benefit of
centralization of esophagectomies in dedicated centers. Early mucosal lesions are
increasingly treated by local ablative therapy. Tumors invading the submucosa are
preferably treated by surgical resection. There is ongoing controversy about the
optimal surgical approach. Positron emission tomography scanning is a promising
tool in the preoperative work-up but needs critical evaluation. The question of
whether chemoradiation with voice preservation (followed by salvage surgery in
case of tumor recurrence) can replace pharyngolaryngectomy in patients with
cervical esophageal cancer is still unanswered. A review of eight randomized
trials demonstrated that chemoradiation as primary treatment of esophageal cancer
provides an absolute reduction of mortality. The addition of new drugs like
paclitaxel and irinotecan into induction regimens for the treatment of advanced
disease results in higher response rates but also in increased toxicity.
Preoperative radiotherapy as single modality treatment does not improve overall
survival, whereas the benefit of preoperative chemotherapy and chemoradiation has
not been proven unequivocally. Several retrospective studies with a small number
of patients suggest that local response parameters like pathologic complete
response and downstaging of regional lymph node (N) status are correlated with
longer survival.
PMID- 17033328
TI - Pancreas.
PMID- 17033329
TI - Receptor biology and intracellular regulatory mechanisms in pancreatic acinar
cells.
AB - Continuing progress is being made in understanding the regulation of pancreatic
acinar cell function by receptor-activated intracellular signaling mechanisms.
Knowledge of how ligands interact at the molecular level with their receptors and
activate heterotrimeric G proteins is increasing. In addition to inositol
trisphosphate, intracellular messengers include cyclic ADP ribose, nicotinic acid
adenine dinucleotide phosphate, arachidonic acid, and diacylglycerol. Ca
signaling involves the interaction of inositol trisphosphate, cyclic ADP ribose,
and nicotinic acid adenine dinucleotide phosphate with distinct subcellular Ca
stores. Ca signals ultimately induce exocytosis of zymogen granules and
identification of the proteins involved on the granule and plasma membrane, and
understanding of their roles is continuing. Other receptor-activated signaling
pathways primarily regulate nonsecretory events. Considerable progress has been
made in understanding how the mammalian target of rapamycin pathway regulates
protein synthesis through translation factors and ribosomal proteins. Other
pathways in acinar cells include the mitogen-activated protein kinases, the
tyrosine kinases, and the transforming growth factor-beta-Smad pathways.
PMID- 17033330
TI - Neurohormonal control of pancreatic exocrine secretion.
AB - The neurohormonal control of pancreatic exocrine secretion is a complex
interaction of multiple pathways involving a large number of gut hormones,
neurotransmitters, and neuropeptides. Recent studies have elucidated a role for
cholecystokinin in the regulation of bicarbonate and fluid secretion from
pancreatic duct cells and suggested that cholecystokinin stimulation of human
pancreatic acinar cells is likely regulated by an indirect mechanism of
stimulation of afferent neurons. Evidence supports the regulation of potassium
channels in rat pancreatic acinar cells by the cyclic AMP-mediated agonist
secretin. Mechanisms for the regulation of cholecystokinin and secretin release
by releasing factors have also been elucidated. The area postrema has been
implicated in the mediation of inhibition of pancreatic secretion by the gut
hormones peptide YY and pancreatic polypeptide. The neurotransmitter serotonin
has been demonstrated to play a role in acid-induced secretin release and in
pancreatic secretion stimulated by luminal factors. The regulation of pancreatic
exocrine secretion by purines, nitric oxide, and gamma-aminobutyric acid as well
as by the neuropeptides pituitary adenylate cyclase-activating peptide, gastrin
releasing peptide, and substance P is reviewed. The role of the central nervous
system in modulating pancreatic secretion is also described. This review
highlights the recent advances in knowledge of the neurohormonal regulation of
pancreatic exocrine secretion.
PMID- 17033331
TI - Genetics and pancreatic disease.
AB - The recognition that variations in the DNA sequence of key genes predispose
individuals to acute pancreatitis, chronic pancreatitis, and pancreatic cancer
represents one of the greatest breakthroughs in pancreas research. This review
highlights recent progress in understanding mutations in the cationic trypsinogen
gene, the pancreatic secretory trypsin inhibitor gene, and the cystic fibrosis
transmembrane conductance regulator gene with respect to pancreatitis. It also
notes progress in the use of microarray technology, classification of chronic
pancreatitis, and predisposition to pancreatic cancer.
PMID- 17033332
TI - Acute pancreatitis.
AB - Acute pancreatitis begins as acute pancreatic injury and may generate a systemic
inflammatory response that evolves into multiorgan failure, leading to death.
Multiple inciting factors such as toxins (alcohol), gallstones, or endoscopic
retrograde cholangiopancreatography result in a cascade of events beginning with
the intra-acinar activation of zymogens and the release of cytokines and other
proinflammatory mediators. Their release is a major determinant of the systemic
inflammatory response and distant organ failure. Attempts to attenuate the
severity of acute pancreatitis by blocking specific inflammatory mediators have
had limited success. This review is divided into experimental acute pancreatitis
and clinical acute pancreatitis. The distinction is maintained because although
animal models of disease have helped define the pathogenesis of acute
pancreatitis, they do not completely reproduce the clinical syndrome of human
acute pancreatitis or guarantee equal success of therapies in humans.
PMID- 17033333
TI - Chronic pancreatitis.
AB - The pathogenesis of idiopathic chronic pancreatitis remains poorly understood
despite the high expectations for ascribing the pancreatic damage in affected
patients to genetic defects. Neither mutations in the cationic trypsinogen gene
nor mutations of the cystic fibrosis conductance regulator gene account for the
chronic pancreatitis noted in most patients with idiopathic chronic pancreatitis.
Attempts to find an autoimmune basis for the pancreatitis in these patients have
not been very successful. The diagnosis of small duct idiopathic chronic
pancreatitis remains a great source of frustration for clinicians. Such patients
with negative results of radiographic studies often cannot be diagnosed unless a
hormone stimulation test such as a secretin test is performed. Although the
porcine biologic form of secretin, which has been used to diagnose chronic
pancreatitis, became unavailable because of widespread use in the treatment of
children with autism, a synthetic form of porcine secretin has now been approved
by the US Food and Drug Administration and is available. The true value of
endoscopic ultrasonography in diagnosing small duct chronic pancreatitis remains
to be fully defined. Endoscopic ultrasonography is becoming the test of choice in
detecting radiographic abnormalities in both the parenchyma and ducts of the
pancreas. Endoscopic ultrasonography-guided celiac plexus block can be performed
relatively easily and very safely. It can provide excellent short-term pain
relief in some patients, but reliable predictors of which patients will be
successful with this therapy are not yet available. Because long-term follow-up
data on the use of endoscopic ultrasonography in this respect are not available,
and because the pain of chronic pancreatitis is, indeed, chronic, the role of
endoscopic ultrasonography-guided celiac plexus block should be limited to
treating those patients with chronic pancreatitis whose pain has not responded to
other modalities.
PMID- 17033334
TI - Pancreatic cancer research: challenges, opportunities, and recent developments.
AB - Advances in the scientific knowledge and medical management of pancreatic cancer
are lagging behind significant discoveries in other tumors. From 2001 to 2002,
the period covered by this review, few but yet important findings have continued
to push this field of medicine ahead. However, the most promising advance made in
pancreatic cancer is the increased awareness of this disease by private and
federal agencies as well as the population at large. In addition, there has been
a remarkable increase in scientific communication among different research groups
around the country. National cooperation among government, philanthropic
organizations, advocacy groups, and scientists offers for the first time a
framework of hope regarding the establishment of a comprehensive plan to fight
this dismal disease. Scientists have responded with renewed enthusiasm, which has
resulted in significant advances in two exciting areas of wide interest in the
field-genetic animal models and postgenomic mechanisms of pancreatic
carcinogenesis. The questions that these studies address and their potential
impact on this field of research are highlighted here.
PMID- 17033335
TI - Pancreatic surgery.
AB - Over the past year considerable progress has been made in the field of pancreatic
surgery. Innovative diagnostic techniques continue to improve the preoperative
staging of pancreatic cancer. For patients with cancer and biliary obstruction,
preoperative biliary stenting appears to increase the incidence of wound
infection after pancreatoduodenectomy but has no effect on other perioperative
complications. New information about the molecular biology of pancreatic cancer
may begin to influence the surgical approach to the disease. More cases of
intraductal papillary mucinous neoplasms are being diagnosed and studied. The
impact of adjuvant chemotherapy and chemoradiation on survival has been more
clearly defined in a large, randomized trial. In patients with sterile acute
necrotizing pancreatitis, conservative nonsurgical management has continued to
produce favorable results. For chronic pancreatitis, surgery appears to diminish
both chronic pain and recurrent episodes of acute pain.
PMID- 17033336
TI - Endoscopic ultrasound of the pancreas: tissue acquisition and intervention.
AB - Endoscopic ultrasound is an established modality for staging gastrointestinal and
pancreatic malignancies. Since the development of the linear array echoendoscope,
the field of interventional endoscopy has continued to evolve as an adjunctive
method to standard endosonography. The ability to sample extraluminal lesions or
lymph nodes has overcome the initial limitations of endoscopic ultrasound and
provided a list of attractive endoscopic ultrasound-guided therapeutic
applications.This review focuses on recent advancements in the field of
interventional endosonography related to the diagnosis and therapy of pancreatic
diseases. In particular, the article reviews the role of endoscopic ultrasound
guided fine-needle aspiration in diagnosing various pancreatic diseases; the role
of endoscopic ultrasound-guided fine-needle injection in delivering neurolytic,
chemotherapeutic, or biologic agents; and emerging procedures like endoscopic
ultrasound-assisted biliary bypass in the setting of malignant biliary
obstruction.
PMID- 17033337
TI - Gastrointestinal epithelial dysplasia: detection with new endoscopic techniques.
AB - Endoscopic detection of dysplasia currently requires either the presence of a
visible lesion (such as a polyp) or the serendipitous sampling of a dysplastic
focus during "blind" surveillance biopsies. To accurately and efficiently examine
large areas of mucosa during surveillance endoscopy, new methods are required to
render dysplasia visible. Spectroscopy and optical coherence tomography are two
technologies under active investigation for this purpose. This review presents
the basic concepts behind these technologies and discusses their utility in the
detection of gastrointestinal dysplasia.
PMID- 17033338
TI - Endoscopic treatment of early gastroesophageal malignancy.
AB - With the routine use of endoscopy, gastroesophageal cancers, which were often
diagnosed in the symptomatic and incurable state, are now being diagnosed at
earlier stages. Treatment of early-stage upper gastrointestinal cancers has
evolved tremendously. Endoscopic therapy has been employed for early-stage
lesions in an attempt to avoid the high morbidity and mortality associated with
current curative procedures such as esophagectomy. These new endoscopic
techniques include endoscopic mucosal resection, photodynamic therapy,
electrocoagulation, and laser therapy. Exciting and novel endoscopic therapeutic
options in diagnosing and treating early gastroesophageal cancers are the focus
of this review.
PMID- 17033340
TI - Bibliography current world literature. Pancreas.
PMID- 17033339
TI - Colon cancer screening strategies.
AB - Screening has been shown to reduce morbidity and mortality related to colorectal
cancer. However, the optimal strategy for population screening for colorectal
cancer has been a topic of heated debate. Recent studies have challenged the
efficacy and cost-effectiveness of current population screening practices. Novel
approaches to improve the assessment of an individual's colorectal cancer risk
and advances in technology are changing our approach to colorectal screening.
This review covers current guidelines for screening for colorectal cancer, recent
advances in cancer risk assessment, and the role of endoscopy, virtual
colonoscopy, and fecal DNA testing in colorectal cancer screening.
PMID- 17033341
TI - Stomach and duodenum.
PMID- 17033342
TI - Gastric secretion.
AB - Overlapping neural, hormonal, and paracrine pathways finely regulate gastric acid
secretion. In rats and guinea pigs, most of the intrinsic neural innervation to
the gastric mucosa originates in the myenteric plexus. In contrast, human
stomachs have a clearly defined submucosal plexus that contains a variety of
transmitters including nitric oxide, vasoactive intestinal peptide (VIP), gastrin
releasing peptide (GRP), substance P, and calcitonin gene-related peptide (CGRP).
Although GRP is known to participate in meal-stimulated acid secretion by
releasing gastrin in a variety of laboratory animals, recent studies were unable
to demonstrate a role for endogenous GRP in meal-stimulated gastrin secretion in
humans. Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of
the secretin-glucagon-VIP family, has been localized to gastric mucosal neurons
and may participate in vagally mediated acid secretion. Two novel peptides,
ghrelin and leptin, have been localized to the stomach. Peripheral administration
of ghrelin stimulates and of leptin inhibits acid secretion. The binding of
secretagogues to parietal cells generates changes in second messengers that
regulate the translocation and activation of the proton pump, HK-ATPase. In
resting cells, HK-ATPase is contained within cytoplasmic tubulovesicles in an
inactive form. At stimulation, the tubulovesicles fuse with the apical canaliculi
and the HK-ATPase is incorporated into the apical membrane where it actively
pumps H ions in exchange for K. Acute infection with Helicobacter pylori results
in hypochlorhydria, whereas chronic infection can cause either hypo- or
hyperchlorhydria, depending on the distribution of the infection and the degree
of corpus gastritis. Recent studies suggest that inflammatory cytokines, produced
in response to the organism, can play a role in the perturbations in acid and
gastrin secretion induced by H. pylori.
PMID- 17033343
TI - Gastroduodenal mucosal defense: an integrated protective response.
AB - The mechanisms by which the gastroduodenal mucosa maintains viability and normal
functioning despite its intensely caustic environment have puzzled clinicians and
investigators alike for at least 150 years. Protective mechanisms have been
divided into three main categories: preepithelial (mucus and bicarbonate
secretion), epithelial (cellular buffering, mucosal architecture and
permeability), and postepithelial mechanisms (mucosal blood flow). Within each
category are many other factors that bear on the ability of the mucosa to
withstand constant changes of luminal pH. We will summarize some of the recent
findings that pertain to the nature and regulation of these defense mechanisms in
the context of a historical overview. Therapeutic implications of these findings
will also be presented in the discussion of novel antiinflammatory compounds
designed to upregulate simultaneously several defensive mechanisms, with the
expectation that gastroduodenal damage will be minimized.
PMID- 17033344
TI - Nonsteroidal antiinflammatory drugs and the stomach.
AB - We review papers on nonsteroidal antiinflammatory drugs (NSAID) and the stomach
published in the 12 months ending April 2002. During this period, some further
developments occurred in the ongoing search for safer antiinflammatory drugs. The
highly selective COX-2 inhibitors (COX-2i) have again exhibited some toxicity in
animal models of repair, but continue to seem a safer alternative than
nonselective inhibitors from the standpoint of the production of human ulcers.
Some data on the gastrointestinal safety of valdecoxib and parecoxib are
available, while co-therapies with acid suppressants to reduce the risk of
conventional NSAID also remain an option (a study comparing lansoprazole with
misoprostol is now published). Whether co-prescribing a proton pump inhibitor
with a COX-2i in patients at higher risk is effective or justified awaits the
results of yet to be completed studies. The nitric oxide (NO)-donating NSAID and
NO-donating aspirin show some distinct promise in animal studies and early-phase
clinical trials.
PMID- 17033345
TI - Peptic ulcer disease.
AB - The introduction of the "Maastricht 2-2000" document provides some guidance with
regard to the management of Helicobacter pylori infection in both primary and
specialist practice settings, albeit primarily in the European setting. The
putative role of H. pylori in gastric carcinogenesis was supported by a further
study. Studies on the natural history of peptic ulcer disease (PUD) highlight the
particular vulnerability of the elderly patient to PUD and its complications, and
focus attention on targeted intervention in this group, particularly the
avoidance of nonsteroidal antiinflammatory drugs (NSAID). Little has evolved with
regard to the introduction of new NSAID, but reports indicate the potential
association of cyclooxygenase-2 (COX 2)-selective agent use with an increased
risk of cardiovascular events. The role of H. pylori and NSAID as risk factors
for peptic ulcer disease and its complications is again explored, and both meta
analysis and clinical studies provide some evidence of their synergistic effect.
The introduction of esomeprazole, the S-isomer of omeprazole, has widened the
clinician's therapeutic choice; the true value of this agent remains to be
determined.
PMID- 17033346
TI - Interventional endoscopy.
AB - Technologic milestones have been achieved in the field of interventional
endoscopy. These have resulted in improved hemostasis, more accurate cancer
staging, safer and less invasive methods of removing gastric neoplasms, and
endoscopic palliation of malignant gastric outlet obstruction via stenting.
However, just as these milestones are achieved, new challenges emerge: (1) How
much sedation can one use safely? (2) What is the risk of transmitting infection
and how can that be prevented? (3) Can scopes be made smaller and more
comfortable? (4) Can optics be improved? (5) Can endoscopic repair of gastric
perforations be safely performed? In this section, we review some of these
issues. First, we will provide an update on the most recent concepts in the field
of light sedation and infection control. Then, a review of the most commonly used
interventional endoscopy procedures, including hemostasis, endosonography,
endoscopic mucosal resection, stenting, and percutaneous gastrostomy tube
placements. Finally, an overview of the ongoing research and development in the
field of interventional endoscopy and how it can improve patient comfort,
diagnostic accuracy, therapeutic efficacy, and training in the future.
PMID- 17033347
TI - Gastric surgery.
AB - Most significant research relating to gastric surgery in the past year has
centered on surgery for gastroesophageal reflux disease (GERD). Antireflux
surgery has become more popular with advanced laparoscopic technology. Two
previously accepted surgical principles have been challenged by current studies:
the importance of division of the short gastrics and the dictum that partial
fundoplication is preferred for patients at risk for dysphagia. Additionally,
risk factors for postoperative dysphagia have been identified, allowing for
better patient selection and education. Further study on the cause of GERD has
shown a positive correlation between pathologic gastroesophageal reflux and those
with hiatal hernia or disordered esophageal peristalsis, although cause or effect
has not yet been established. Literature relating to bariatric surgery has
confirmed the safety and efficacy of the laparoscopic Roux-en-Y gastric bypass,
and several papers address the appropriateness of prophylactic cholecystectomy in
these patients. The role of laparoscopic surgery for treatment of perforated
peptic ulcer disease has now been validated, with subsequent eradication of
Helicobacter pylori infection. The relationship of H. pylori infection to acutely
bleeding ulcers is less clear. Indications for ulcer surgery are predominantly
limited now to perforation and bleeding because of the availability of effective
acid-reducing medications and recognition of the role of H. pylori infection.
PMID- 17033348
TI - Pediatric disorders of the stomach.
AB - Disorders of the stomach represent a significant portion of the practice of
pediatric gastroenterology. Controversy still exists in the appropriate
management of children with abdominal pain and vomiting and large gaps remain in
our understanding of the physiology and pathophysiology of the stomach in
children. Nevertheless, we have made significant progress in understanding
Helicobacter pylori infection and gastric motility in the pediatric population.
PMID- 17033349
TI - Immunology.
PMID- 17033350
TI - Immunologic basis for diarrhea.
AB - Diarrhea is a common sequela of deregulated immune pathways underlying the wide
range of intestinal acute and chronic diseases. The ongoing investigation of
novel immune components and susceptibility factors allows better understanding of
these pathologic mechanisms and continues to advance therapeutic options.
PMID- 17033351
TI - Toll-like receptors and gastrointestinal diseases: from bench to bedside?
AB - The family of Toll-like receptors (TLRs) plays a key role in mediating innate
immune responses to numerous luminal commensal- and pathogen-derived pattern
molecules by the intestinal mucosa. Recent findings have identified several
ligands recognized by TLRs as well as the complex downstream signaling effects
resulting from activation of these receptors. Understanding is emerging of the
importance of TLRs in mucosal host defense-potentially triggering
gastrointestinal diseases.
PMID- 17033352
TI - Revisiting the "hygiene hypothesis" in gastrointestinal allergy.
AB - The "hygiene hypothesis" in its original form hypothesized that infection in
early childhood acquired through unhygienic contact with siblings or the mother
may prevent the development of allergic disease. Several recent epidemiologic
surveys showing an inverse relationship between the frequency of infectious
disease and the incidence of allergic diseases lend support to this hypothesis.
Allergen sensitization of the immune system can occur early in utero against a
background of neonatal commitment to a Th2 immune response involving the
production of Th2 cytokines (eg, interleukin (IL)-4, IL-5, IL-13) that are the
principal mediators of allergic inflammation. Continued allergen exposure is
associated with predominantly CD4+ Th2 cell proliferation but does not exclude a
minor Th1 allergen-specific subpopulation that can be further expanded
nonspecifically and polyclonally by microbial superantigens or as bystanders, by
interferon-gamma (IFN-gamma) and IL-2 released from Th1 effectors responding to
antigens associated with infectious pathogens. Th1 cytokines can also subvert
allergen-specific Th2 lymphocytes to become allergen-specific Th1 cells-a process
reminiscent of the increased tendency of the maturing immune system of growing
adults to mount a Th1 response to some environmental and dietary antigens. Unlike
Th2 cytokines, IFN-gamma and IL-2 inhibit B-cell production of IgE and, hence,
delimit the capacity of mast cells to degranulate and release allergenic
mediators. The ability of infectious agents through their danger signals to
initiate a Th1 response that deviates the Th2 allergenic bias is the basis of the
hygiene hypothesis.
PMID- 17033353
TI - T helper cell subclasses and clinical disease states.
AB - The functionally different CD4 T helper cell subsets known as T helper 1 (Th1)
and T helper 2 (Th2) display a unique and different cytokine profile. Abnormal
skewing toward Th1 or Th2 cells has been suggested to play an important role in
the pathogenesis of autoimmune disorders and in inflammatory and allergic
diseases. The Th1/Th2 paradigm continues to serve as a model to understand the
pathogenesis of several pathologic conditions and provides the rationale for the
development of new strategies for treating and preventing these diseases. Over
the past year, efforts have continued to increase our understanding of the
mechanisms underlying the development and regulation of Th cells and their
pathogenic role and therapeutic potential in the induction and treatment of
clinic diseases. Several teams of researchers have further examined the
association of Th1/Th2 inducing factors and allergic disease and intestinal
inflammatory diseases. The protective effect of helminth infection on allergy and
the role of regulatory T cells in both Th1- and Th2-mediated diseases have been
further examined.
PMID- 17033354
TI - Protective nutrients.
AB - Recognition that specific nutrients can be beneficial when consumed in amounts
above the accepted daily requirements has provided a major impetus for the
critical examination of dietary approaches with single or multiple nutrient
supplements chosen to modulate the inflammatory response, enhance immune
function, or improve the blood-gut barrier. Patients suffering the effects of
hypercatabolism caused by surgery, cancer, or extensive burns are prime
candidates for immunonutrition, as the intervention has come to be known, as are
immunosuppressed patients with the human immunodeficiency virus or other
overwhelming infections. This review focuses on key nutrients used in clinical
trials for which a body of information on the mode of action and metabolic
pathways is available. The topics covered include the amino acids, glutamine and
arginine; omega-3 fatty acids, eicosapentaenoic acid and docosahexanoic acid;
vitamin A; and zinc. Lastly, we address the area of pre- and probiotics and how
"friendly" microorganisms are being incorporated into therapeutic regimens aimed
at sustaining health. The use of immunonutrition requires judicious consideration
of the potential undesirable effects of certain additives in clinical settings
where enhanced immune responsiveness can translate into tissue damage and altered
mucosal defenses.
PMID- 17033356
TI - Bibliography current world literature. Stomach and duodenum.
PMID- 17033355
TI - Update on cancer vaccines.
AB - The development of vaccines to induce tumor-specific immunity in patients with
cancer has as emerged as a major area of investigation. The identification of
antigens uniquely expressed by tumor cells and a heightened understanding of
tumor immunology have resulted in efforts to activate host immunity to recognize
and reject tumor cells. Tumor-associated antigens and peptides, genes encoding
tumor antigens, and modified whole tumor cells have been used in preclinical
studies with provocative results. Potent antigen-presenting cells, known as
dendritic cells, have also been modified using peptides, genetic material, or
whole tumor cells to present tumor antigens in the context of co-stimulation to
overcome tolerance and induce tumor-specific cell killing. Promising data
generated from the preclinical evaluation of cancer vaccines have resulted in the
initiation of clinical trials to define the associated toxicity profile,
immunologic response, and clinical impact of this treatment approach. We
summarize the preclinical and clinical experience in this expanding area of
investigation. Cancer vaccines hold much promise; however, many unresolved
questions remain in the effort to generate a clinically meaningful treatment
strategy.
PMID- 17033357
TI - HIV infection and AIDS.
PMID- 17033358
TI - The role of behavioral research in HIV/AIDS prevention.
AB - Behavioral and social research has been at the core of HIV/AIDS prevention
efforts, by identifying the factors that contribute to the risk of transmission
and by developing effective behavioral interventions to modify that risk. The
historical focus of behavior-change strategies on decision-making processes
within the individual has evolved to include more attention to the dynamics of
interpersonal relationships and the sociocultural contexts in which HIV-related
risk behaviors occur.
PMID- 17033359
TI - Recent findings about the heterosexual transmission of HIV and AIDS.
AB - Study of the heterosexual transmission of HIV has shifted focus from the
behavioral and demographic risk factors associated with HIV to the biological and
molecular factors. Although factors such as genetic predisposition may be
immutable, others such as co-infection with sexually transmitted diseases are
modifiable by the use of treatment. The effect of antiretroviral treatment is
also promising but deserves more study, as does the use of contraception and
microbicides (chemical barriers meant for intravaginal use).
PMID- 17033360
TI - The HIV epidemic in Italy.
AB - The implementation of surveillance systems for HIV and of large cohort studies
have allowed for the construction of models that more accurately describe the HIV
epidemic. This review focuses on changes in the epidemiological pattern, and the
effect of changes in behaviour and of antiretroviral therapy.
PMID- 17033361
TI - Immunizations during HIV infection.
AB - The safety and efficacy of immunizing HIV-infected persons for other diseases has
been controversial. Transient increases in HIV viral load have been reported in
some but not all studies of immunization, and are unlikely to have adverse
clinical consequences, particularly in the era of more active antiretroviral
therapy. Although the serological response to immunization is reduced in the HIV
infected host, recent data suggest that it has some clinical efficacy.
PMID- 17033362
TI - AIDS oncology.
AB - New diagnostic approaches to primary central nervous system lymphoma have been
developed that may make brain biopsy unnecessary in many instances. Reduced-dose
chemotherapy for non-Hodgkin's lymphoma has been shown to be advantageous in a
randomized controlled trial. New agents for the treatment of Kaposi's sarcoma are
available. Adoptive cellular immunotherapy has been shown to be effective in the
treatment and prevention of Epstein-Barr virus-associated B-cell lymphomas in
bone marrow transplant recipients, and may have promise in AIDS patients.
PMID- 17033363
TI - Sexually transmitted diseases and urinary tract infections.
PMID- 17033364
TI - Subclinical herpes virus reactivation and latency.
AB - Although there has been considerable refinement in our understanding of the
processes underlying the establishment and maintenance of latency, important
research questions remain. Results from various workers imply that the
establishment of latency may be a dynamic process and may offer possible
therapeutic targets. The role played by the latency-associated transcripts appear
to be important in both establishing latency and in aiding reactivation. Recent
work has shown that reactivation in vivo is much more frequent than previously
thought and leads principally to subclinical viral shedding. Factors influencing
subclinical shedding for most patient groups and the response and limitation of
therapy have been clearly determined.
PMID- 17033365
TI - Chlamydia immunology.
AB - Chlamydia trachomatis infection elicits both antibody and cell-mediated immune
responses. Neutralizing antibody is serovar-specific and dependent upon
conformational epitopes. CD4 lymphocytes (predominantly type 1 helper T cells)
function in protection, but the role played by CD8 lymphocytes in protection or
pathology is less well defined. Local cytokine induction is correlated with
inflammation and effector influx, and may direct the acquired immune response.
PMID- 17033366
TI - Genotyping of Neisseria gonorrhoeae.
AB - Genotyping of Neisseria gonorrhoeae has proved highly discriminatory. It has been
used to differentiate between isolates of the same serovar, to determine the
genetic relatedness of antibiotic resistant isolates and to identify isolates
from sexual contacts. This level of resolution has been possible because
Neisseria gonorrhoeae exhibits a high degree of genetic variability. The validity
of using any typing technique to study temporal or geographical differences of an
organism known to be non-clonal should, however, be carefully considered.
PMID- 17033367
TI - Ethnicity and sexually transmitted infections.
AB - Public health workers have long recognized that sexually transmitted diseases are
differentially distributed within the population, with the highest rates observed
in ethnic minorities. Incidence rates for bacterial diseases, such as gonorrhea
and chlamydia, may be five to 10 times higher than in the general population, and
two to three times higher for prevalent viral infections such as genital herpes.
Unless ethnic group-specific analyses are performed, however, the elevated rates
may not be discernible. These groups are also often at highest risk for
heterosexual HIV transmission. Understanding the differential risks faced by
ethnic groups is a critical component of developing appropriate behavioral and
healthcare access interventions.
PMID- 17033368
TI - Epidemic syphilis in the newly independent states of the former Soviet Union.
AB - Major syphilis epidemics are occurring in the former Soviet Union as a result of
the effects of rapid political, economic and social reform on clinical services
and sexual behaviour. Together with epidemics of injecting drug use-associated
HIV infection, they pose a major threat of large sexually transmitted HIV
epidemics. Economic realism demands that control efforts address the market and
ideological forces driving the development of interventions, as well as technical
aspects of their design.
PMID- 17033369
TI - Prospects for human papillomavirus vaccine development: emerging HPV vaccines.
AB - This review concentrates on recent advances in human papillomavirus vaccine
development. Strategies for prophylactic HPV subunit vaccines utilizing
recombinantly synthesized, immunogenic virus-like particles are discussed.
Therapeutic strategies focusing on the induction of cell-mediated immunity and
gene manipulation for the treatment of established HPV-associated disease are
also reviewed.
PMID- 17033370
TI - Complicated urinary tract infection.
AB - Urinary tract infection is the second commonest infection encountered in both the
community and the hospital setting. In order to avoid complications and to
minimize the unnecessary use of antibiotics, it is essential to have a useful and
rapid screening test to identify urinary tract infection. The presence of nitrite
and leukocyte esterase on urinalysis is such a test. Symptomatic bacteriuria
requires prompt treatment and pyelonephritis should be treated for 10-14 days,
whereas asymptomatic catheter and non-catheter bacteriuria should not be treated,
except in the setting of pregnancy and in childhood.
PMID- 17033371
TI - Skin and soft tissue infections.
PMID- 17033372
TI - Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, cytokines, growth
factors and HIV in pathogenesis of Kaposi's sarcoma.
AB - Epidemiological studies have strengthened the case for Kaposi sarcoma-associated
herpesvirus/human herpesvirus 8 being the long-sought Kaposi sarcoma agent, but
have also pointed to a role for other co-factors. Like other tumour viruses,
Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 establishes a latent
(persistent) infection in Kaposi sarcoma-spindle (tumorous) cells, but can also
undergo lytic replication in these and other cell types. Several latent and lytic
viral genes may play a role in the pathogenesis of Kaposi's sarcoma. Although
Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 contains at least two
genes with transforming properties, it has not yet been shown to be oncogenic in
animals. This, and other studies on inflammatory/angiogenic cellular and viral
cytokines as well as HIV-Tat, emphasizes the multifactorial complexity of the
pathogenesis of Kaposi's sarcoma.
PMID- 17033373
TI - Cutaneous parasites.
AB - Recent developments in leishmanial research include better survey procedures to
determine risk factors in the community. Community-based scabies control is seen
as the only way to reduce the morbidity caused by this infection in developing
countries. The diagnosis of both infections, and of head lice, however, continues
to provide problems for the physician.
PMID- 17033374
TI - Skin, hair and nail fungal infections.
AB - Fungal infections of the skin, hair and nails are among the most common skin
diseases. The increased incidence of these infections in recent years has been
attributed to the large number of immunocompromised patients, life-style changes
(greater attendance at gymnasiums, public baths, etc.), the use of
chemotherapeutic agents, and the greater presence of elderly people in the
general population. Superficial fungal infections were also the most frequent and
troublesome dermatological condition occurring among US forces during the war in
Vietnam.
PMID- 17033375
TI - Dermatological infections in the immunocompromised host.
AB - The data from the most recent studies concerning infection with human herpes
virus 8 strongly support a pathogenic role for this virus in the tumoral
hyperplasia which is a feature of Kaposi's sarcoma. The results from the first
studies of the sensitivity of human herpes virus 8 to antiviral drugs were also
published last year. This review also concerns bacterial and mycobacterial
infections showing unusual presentation, important trials in the prevention of
infection with varicella zoster virus by using vaccination in children with
leukemia, and a controlled therapeutic study in HIV-infected patients presenting
with early syphilis.
PMID- 17033376
TI - Skin and soft tissue infection: necrotizing fasciitis.
AB - The incidence of necrotizing fasciitis has increased in the past decade as a
result of the resurgence severe group A streptococcal infection. Mortality has
remained unchanged over the past 60 years, supporting the notion that immune
modulators, such as intravenous immunoglobulin, are required to alter the
physiological process during the early stages of infection.
PMID- 17033377
TI - Respiratory infections.
PMID- 17033378
TI - New polymerase chain reaction-based diagnostic techniques for bacterial
respiratory infection.
AB - Polymerase chain reaction protocols are now available for the diagnosis of all of
the major bacterial respiratory tract pathogens. Molecular techniques are also
being used to determine the susceptibility of Streptococcus pneumoniae and
Mycobacterium tuberculosis. In addition, polymerase chain reaction-based
diagnosis will find a place in the investigation of the epidemiology of some
pathogens such as Bordetella pertussis and Chlamydia pneumoniae. The added
sensitivity will allow the detection of mild or asymptomatic cases or carriers
who may play a role in sustaining the pathogen in the community.
PMID- 17033379
TI - Antibiotic resistance in respiratory pathogens.
AB - Antibiotic resistance in respiratory pathogens has dramatically increased during
recent years. Resistance to penicillin and multiple antimicrobial agents in
pneumococci and resistance to ampicillin in Moraxella catarrhalis and Haemophilus
influenzae, as a result of betalactamase production, have become highly prevalent
worldwide. The emergence of multiple drug-resistant tuberculosis in different
countries is of concern, and has become a therapeutic challenge.
PMID- 17033380
TI - Community-acquired pneumonia in adults.
AB - Efforts to reduce hospitalization or the length of stay are common topics in
papers published last year. Chlamydia pneumoniae is now recognized worldwide as a
common pathogen in community-acquired pneumonia. A great variation in the
frequency of various pathogens is found in different countries, stressing the
importance of ascertaining the aetiological and epidemiological situation in each
respective country.
PMID- 17033381
TI - Hospital-acquired pneumonia: recent advances in diagnosis, microbiology and
treatment.
AB - Nosocomial or hospital-acquired pneumonia occurs frequently, despite preventative
measures and advances in diagnostic procedures and treatment of this severe
infection. This article will highlight the recent literature with emphasis on
significant publications and advances in the area of pneumonia pathogenesis,
microbiology, diagnosis, and response to antimicrobial therapy.
PMID- 17033382
TI - Treatment for mycobacterial infections.
AB - Mycobacterium tuberculosis remains the most important global cause of
mycobacterial disease in humans. The central roles of consistent delivery,
adherence to therapy, and built-in audit of practice have recently received heavy
emphasis in the treatment of M. tuberculosis, particularly in new guidelines from
the World Health Organization. The management of mycobacterial disease in the
context of HIV infection continues to pose problems, particularly in resource
poor settings. The most significant development for the clinical management of
HIV-associated M. tuberculosis infection in the past year has been the
establishment of the efficacy of isoniazid monotherapy as preventive therapy,
after the publication of three new randomized, placebo-controlled trials.
PMID- 17033383
TI - The diagnosis and management of pleural empyema.
AB - The diagnosis and management of pleural infection continues to improve steadily.
Recent advances include: newer, smaller, and more comfortable chest drainage
catheters; improved pleural pus drainage with the aid of intrapleural
fibrinolytics; and improved surgical procedures including thoracoscopic surgery.
The optimal size of chest drainage tube remains a matter of debate, with no large
data sets available to clarify the optimal tube size. In contrast, there are now
small controlled trials of sound basic methodology which suggest a therapeutic
role for both fibrinolytics and thoracoscopy. Studies large enough to establish
clearly the efficacy and safety of these approaches are now at the planning and
recruitment stage.
PMID- 17033384
TI - Generalized infections.
PMID- 17033385
TI - Escherichia coli O157 and human disease.
AB - In the 15 years since its discovery, Escherichia coli O157 infection has become
an important public health problem of the developed world, causing concern not
only because of its rise in incidence, but also because of the severity of its
complications. Research is still at an evolutionary phase, often providing more
questions than answers. The most recent developments in human infection are
presented in this review.
PMID- 17033386
TI - Human microsporidioses.
AB - Recent developments in microsporidiosis research include the increased
utilization of molecular techniques for the investigation of clinical specimens
as well as for epidemiological and phylogenetic studies. Special attention is
given to studies reporting severe disseminated microsporidioses involving most
organs in AIDS patients, and the increased number of HIV-seronegative and
immunocompetent individuals with microsporidiosis. The potential efficacy of
fumagillin (Sanofi Recherche, Gentilly, France) in infections caused by
Enterocytozoon bieneusi, and the remission of intestinal microsporidiosis in HIV
infected patients with antiretroviral therapy are also highlighted.
PMID- 17033387
TI - Ehrlichioses: emerging infections.
AB - Human monocytic and granulocytic ehrlichioses are emerging tick-borne infections.
Each is caused by different, but related, obligate intracellular bacteria. Recent
advances have clarified the classification of these species and progress in
understanding their pathogenesis has begun. There is, however, still much to
learn about the clinical spectrum, diagnosis, management, and treatment of these
unusual infections.
PMID- 17033388
TI - Bartonella infections: diagnostic and management issues.
AB - Bartonella species are emerging pathogens. Renewed interest in this group of
bacteria has been highlighted by the recent description of new species, which are
pathogenic for humans (Bartonella elizabethae and Bartonella clarridgeae), and
their association with an increasing number of clinical manifestations, the more
prevalent being cat scratch disease, bacillary angiomatosis, and culture-negative
endocarditis.
PMID- 17033390
TI - Immunity and host response.
PMID- 17033389
TI - Human T-cell lymphotrophic virus type 1: infections and pathogenesis.
AB - The number of clinical manifestations associated with human T-cell lymphotrophic
virus type 1 infection continues to expand, as does the number of regulatory
genes that human T-cell lymphotrophic virus 1 either transactivates or binds to
directly. The relationship with the immunogenetics of the host is becoming more
crucial with specific human leukocyte antigen types determining the risk of
developing tropical spastic paraparesis/human T-cell lymphotrophic virus 1
associated myelopathy or adult T-cell leukaemia and lymphoma. Perhaps
surprisingly, given the complexity of the virus-host interaction and the poor
response to treatment of human T-cell lymphotrophic virus 1 associated conditions
so far, a really remarkable response to azathioprine and alpha-interferon is
reported for patients with adult T-cell leukaemia. Other reverse transcriptase
inhibitors may also be effective in adult T-cell leukaemia and lymphoma and
tropical spastic paraparesis/human T-cell lymphotrophic virus 1 associated
myelopathy, although the fact that adult T-cell leukaemia is a monoclonal
expansion disease that no longer requires virus replication per se, raises the
question as to whether or not azathioprine is acting as an anti-cancer agent,
which was its original role before the anti-HIV screening programme.
PMID- 17033391
TI - Fc receptor and complement receptor-mediated phagocytosis in host defence.
AB - In the past few years significant progress in the area of phagocyte biology has
been made in unravelling the mechanism of phagocytosis. In this review we discuss
the characteristics and functions of complement and Fc receptors and the role
they play as bridges between humoral and cellular immunity. We focus on the
function of these receptors in a comprehensive way and propose a novel model to
explain the integration of various signals for the optimal functioning of
phagocytic cells.
PMID- 17033392
TI - Monocyte deactivation in septic shock.
AB - Septic shock is a complicated syndrome in which pro-inflammatory and anti
inflammatory processes are dynamically interconnected and regulated. Central to
these processes is the monocyte, which produces large quantities of pro
inflammatory cytokines in the presence of bacterial products. During the course
of sepsis, the production of compensatory anti-inflammatory mechanisms may
deactivate monocytes and lead to a state of paralysis. This situation is in fact
similar but not identical to that known as tolerance, in which normal monocytes
prechallenged with lipopolysaccharide do not respond to a second challenge of
lipopolysaccharide. Here, we review some of the cellular mechanisms that may lead
to monocyte deactivation and discuss the clinical implications they may have.
PMID- 17033393
TI - Novel therapies in streptococcal toxic shock syndrome: attenuation of virulence
factor expression and modulation of the host response.
AB - The systemic manifestations of severe invasive group A streptococcal infections,
such as streptococcal toxic shock syndrome, are mediated by an overwhelming
inflammatory response induced by streptococcal superantigens and other virulence
factors. The high mortality rates associated with streptococcal toxic shock
syndrome demonstrate a need for better therapy in these diseases. Novel
strategies to attenuate or prevent streptococcal toxic shock syndrome at
different stages of illness have been proposed. The most promising therapies
include agents that by various mechanisms attenuate the inflammatory response or
the action of streptococcal toxins/superantigens, or both.
PMID- 17033394
TI - Hepatitis C.
AB - Hepatitis C virus commonly causes chronic liver disease. Chronicity as a result
of the failure of T-cell-mediated immunity, liver damage caused by cytotoxic T
lymphocytes, and the evolution of genetic diversity characterize hepatitis C
infection. Progression, typically silent, is determined by sex, age, alcohol and
immune status. Interferon and ribavirin are effective in the substantial minority
of patients with less advanced fibrosis and lower hepatitis C viral loads.
PMID- 17033395
TI - Does Chlamydia pneumoniae cause coronary heart disease?
AB - Evidence continues to accumulate to support a role for Chlamydia pneumoniae in
the pathogenesis of atherosclerosis, and in particular, coronary heart disease.
In an analysis of 18 seroepidemiological studies, individuals with high-titer
antibodies to Chlamydia pneumoniae have at least a twofold or larger odds ratio
for coronary heart disease compared with seronegative individuals. In addition,
viable Chlamydia pneumoniae has been cultured directly from atherosclerotic
tissue, and has been demonstrated by polymerase chain reaction,
immunocytochemistry, and electron microscopy in nearly 50% of atheromatous
lesions, but in only 5% of control samples. Chlamydia pneumoniae has been shown
to infect and reproduce in vitro in human smooth muscle cells, coronary artery
endothelial cells, and macrophages, and has been shown to induce procoagulant
activity and platelet adhesion factors known to contribute to the pathogenesis of
atherosclerosis. Furthermore, Chlamydia pneumoniae has been identified in
atherosclerotic tissue in two experimental animal models. Finally, two pilot
antibiotic trials of post-myocardial infarction patients receiving antibiotics
effective against Chlamydia pneumoniae have demonstrated a fivefold reduction in
cardiovascular events compared with those patients receiving placebo. Although a
causal effect has not been proved, the relationship between Chlamydia pneumoniae
and atherosclerosis continues to grow and to stimulate more definitive studies.
PMID- 17033396
TI - Experimental treatments of meningococcal sepsis.
PMID- 17033397
TI - The emerging spectrum of tickborne infections.
AB - Recent advances in tickborne infections have generally served to reiterate
existing clinical truisms: most tickborne infections must be diagnosed on
clinical grounds alone, because laboratory testing is rarely useful in early
illness; the usual presumptive therapy for treatable tickborne infections is
doxycycline, which may be used even in childhood; except in very young infants,
most tickborne infections are tolerated by children, whose outcome is generally
benign.
PMID- 17033398
TI - Dengue: a continuing challenge for molecular biology.
AB - Ten years ago Scott Halstead published a seminal review outlining the challenge
to science provided by dengue. Our review summarizes recent efforts to meet this
challenge and discusses the potential practical implications of basic research.
One major long-term goal is the development of a vaccine, and several different
strategies are currently being advanced. Clinical studies on dengue continue to
help physicians make rational choices in disease management.
PMID- 17033399
TI - Prevention of group B streptococcal infection in neonates.
AB - Most publications on the subject of group B streptococcus since December 1996
have concentrated on supporting and to some degree extending our existing
knowledge of the epidemiology of group B streptococcus and of intrapartum
antimicrobial prophylaxis, which is the only approach available for reducing the
incidence of group B streptococcal infection. Of greatest importance clinically
are the reviews and studies on intrapartum antimicrobial prophylaxis, which
continue to show that this is a worthwhile intervention as it significantly
reduces the incidence of early onset group B streptococcal sepsis. The best
approach to the detection of carriage is also covered, as is the changing
epidemiology as a result of the implementation of intrapartum antimicrobial
prophylaxis in some centres. Finally, the prospect of a vaccine is discussed.
PMID- 17033400
TI - Childhood tuberculosis: advances in immunopathogenesis, treatment and prevention.
AB - Tuberculosis in childhood is an important cause of mortality worldwide. The
disease is difficult to diagnose and the underlying immune mechanisms are poorly
understood. Advances in the application of molecular genetic tools, as
illustrated by the recent completion of the genome sequence of Mycobacterium
tuberculosis, provide opportunities for the development of improved diagnostic
tools and vaccines for tuberculosis. It is important that research efforts in
this area should include consideration of the unique problems and possibilities
related to the control of tuberculosis in children.
PMID- 17033401
TI - A reappraisal of current approaches to the management of fungal infections in
neutropenic patients.
PMID- 17033402
TI - Fever associated with chemotherapy-induced neutropenia: a review of current
therapeutic approaches.
AB - The numbers of cancer patients subjected to chemotherapy-induced neutropenia
steadily grows as the new indications for systemic treatment expand. When these
patients develop fever, or other signs of infection, they must receive immediate
medical attention. This paper discusses the current therapeutic strategy for
febrile neutropenia in cancer patients and reviews some of the newer approaches,
which include empirical monotherapy, outpatient protocols, antibiotic prophylaxis
and the use of haematopoietic growth factors.
PMID- 17033403
TI - Infections in solid organ transplant recipients.
AB - Delineation of the pathogenic potential and assessment of the efficacy of newer
therapeutic modalities for a number of viruses have been among the more notable
developments in solid organ transplant infections within the past year. Infection
caused by the novel herpesvirus, human herpesvirus-6, was proposed to be a
significant cause of fever of unknown origin and a predictor of subsequent
cytomegalovirus infection. Interleukin-2-primed isologous T lymphocytes led to
the complete regression of Epstein-Barr virus-positive post-transplant
lymphoproliferative disorder. Although interferon-alpha alone was shown to be
largely ineffective as prophylaxis and treatment for hepatitis C virus hepatitis,
the combination of interferon-alpha and ribavirin appeared promising.
Documentation within the past year, however, of lamivudine and famciclovir
resistance in hepatitis B virus, ganciclovir resistance in cytomegalovirus, and
azole resistance in Candida, is a sobering reminder that antimicrobial
prophylaxis must be utilized rationally and selectively.
PMID- 17033404
TI - Infection in patients with congenital immune deficiencies.
AB - We review recent developments in the pathogenesis of the major
immunodeficiencies, the pathogens involved, and new diagnostic and treatment
options. Early diagnosis and prophylaxis are the mainstays in the current
management of these immunological disorders. New advances, including the use of
cytokines and growth factors, molecular diagnosis and a better understanding of
the immunopathogenesis of infections, are discussed.
PMID- 17033405
TI - Infections due to the herpesvirus group in immunocompromised patients.
AB - Herpesvirus infections remain a significant cause of morbidity and mortality in
iatrogenically immunosuppressed individuals despite the considerable progress
achieved in recent years by the use of anti-viral drugs. Human cytomegalovirus is
particularly important in this context and major advances have been made towards
understanding the basis of cytomegalovirus latency and persistence. At the same
time efforts continue to develop optimal virus detection in immunosuppressed
individuals with a view to improving current therapeutic policies, and to define
the emerging problem of anti-viral drug resistance. Finally, the evidence is
gathering that the newest additions to the human herpesvirus family, i.e. human
herpesviruses-6, -7 and -8, are significant pathogens in the immunosuppressed.
PMID- 17033406
TI - Imaging in the diagnosis of infections in immunocompromised patients.
AB - Early use of CT and MRI helps to diagnose infection in immuno-compromised
patients earlier and more precisely. Anti-fungal therapy can now be instituted in
the knowledge that there is scan proven fungal disease and withheld when scans
indicate other pathology. The optimal way to utilise these tests is described.
PMID- 17033407
TI - Unusual infections and new diagnostic methods in the immunocompromised host.
AB - Over the past year, considerable progress has been made in the understanding of
the pathogenesis of a variety of infections found in the immunocompromised host.
Some interesting organisms not previously described in this setting have been
implicated as being causative of disease. Molecular methods for the detection of
many organisms increase our ability to diagnose infection in these patients, and
also make the accurate monitoring of infection during treatment possible.
PMID- 17033408
TI - Antibiotic resistance--the combat zone.
PMID- 17033409
TI - Guidelines, policies and the Internet.
AB - The Internet may become a powerful tool in the implementation of medical
guidelines, but experience with this new technology is rather limited. Scientific
assessments of how the Internet may cover the needs of healthcare professionals
are still not available, but concerns about data reliability and the management
of information abundance are already being raised.
PMID- 17033410
TI - Infection control in countries with limited resources.
AB - Considerable progress has been made in the development of effective hospital
infection control programs in countries with limited resources, most notably in
Asia and Latin America. National nosocomial infection surveillance methods are
now used in a variety of countries, particularly in Brazil, and offer a better
measure for evaluating the rates of common nosocomial infections and gauging the
effect of prevention efforts. Extending these achievements to other hospitals
that presently lack effective programs is an organizational and logistic
challenge for the future. Newer, daunting problems are the prevention and control
of antimicrobial resistance and nosocomial transmission of tuberculosis.
Improvements in the protection of healthcare workers from exposure to bloodborne
pathogens, research regarding the safety and efficacy of the reuse of single-use
items, and more practical and affordable methods for sterilization and
disinfection are needed.
PMID- 17033411
TI - Semmelweis' sesquicentennial: a little-noted anniversary of handwashing.
AB - This review describes Semmelweis' achievement 150 years ago. User acceptability
of hand disinfectants has been improved, but Semmelweis' observation that
handwashing, in contrast to hygienic hand disinfection, is not always
sufficiently effective, is not yet generally acknowledged, and the compliance of
medical personnel to the rules of hand hygiene still remains an educational
problem to be solved.
PMID- 17033412
TI - Approaches to the diagnosis and prevention of intravascular catheter-related
infection.
AB - Intravascular catheter-related infections remain a significant cause of morbidity
and mortality despite clear guidelines on insertion and care, which should aid in
their prevention. New approaches in the diagnosis of these infections, which do
not require removal of the catheter, and novel technologies, including the
application of antimicrobial agents to the catheter, have demonstrated some
degree of success in prevention.
PMID- 17033413
TI - Surgical site infections: the cutting edge.
AB - Surgical site infections are common and many are preventable. It is critical to
understand the factors that influence these infections in order to create
appropriate strategies to reduce this risk. Recent developments in this area and
recommendations are presented.
PMID- 17033414
TI - Novel strategies for the use of antibiotics.
AB - Recent data have suggested an extension of the use of nasal mupirocin into the
area of infection prevention in cardiac surgery. Randomized placebo-controlled
studies of preoperative mupirocin are now required to confirm these results. Two
randomized controlled studies of either antiseptics or antibiotics impregnated or
coating central catheters have shown advantages in terms of preventing infection
compared with placebo. The role played by chlorhexidine-coated peripheral
catheters is less clear.
PMID- 17033415
TI - Occupationally acquired infections and the healthcare worker.
AB - Much of the recent research related to occupational infections in healthcare
workers has focused on the evaluation of the effectiveness of preventive
measures, the cost-effectiveness of such measures, and alternative approaches to
preventing common occupational infections. This article reviews recent
information on healthcare workers about occupationally acquired diseases and
considers the risks from unusual or re-emerging pathogens. Among recent advances
of note are effective post-exposure prophylaxis for HIV, approaches to achieving
immunity to hepatitis B in vaccine non-responders, better diagnostic tests for
hepatitis C and improved equipment for preventing blood exposure and
tuberculosis.
PMID- 17033417
TI - Malaria in 1998: advances in diagnosis, drugs and vaccine development.
AB - Malaria threatens almost half the world's population. Although a concerted
worldwide effort might control this disease, the reality is that inadequate and
ineffective laboratory diagnosis and treatment conspire in the yearly deaths of
2,000,000 children from malaria. The failure to institute and implement
safeguards to maintain the efficacy of new antimalarial drugs is likely to
accelerate the emergence of untreatable malaria, creating an ominous parallel to
tuberculosis. There is hope. Field expedient, simple and affordable malaria
diagnostics are at hand. Artemisinin derivatives remain surprisingly effective
against the multiply drug-resistant falciparum malaria of southeast Asia, despite
the widespread and unregulated use of these agents. Human trials have begun of
WR238605, a promising primaquine replacement that has prophylactic, treatment and
transmission-blocking potential. After demonstrating unprecedented protection
against homologous challenge, RTS,S, a new sporozite-based malaria vaccine
candidate, is now in field trials.
PMID- 17033418
TI - Sequencing the genome of Plasmodium falciparum.
AB - Advances in microbial genomic sequencing have the potential to revolutionize the
control of infectious diseases. Recently, a consortium of researchers and funding
agencies from the United States and Great Britain have embarked on a project to
sequence the genome from Plasmodium falciparum, the most important cause of human
malaria. The Malaria Genome Sequencing Project has reached an important milestone
with the completion of the entire DNA sequence and annotation of chromosome 2, a
950 kilobase chromosome of Plasmodium falciparum. This review article will
provide an overview of the malaria genome sequencing project, highlight progress
in the field of microbial sequencing, and suggest new directions for future
malaria research.
PMID- 17033419
TI - Recent advances in leishmaniasis.
AB - There has been a rapid increase in the understanding of the mechanisms whereby
Leishmania infects mammalian hosts and evades the immune response. This, in turn,
is driving the search for vaccines against leishmaniasis. Leishmaniasis is an
infection in which the dichotomy between cellular (T-helper cell type 1) and
humoral (T-helper cell type 2) responses is clearly characterized in murine
models, but is unclear in humans. The diagnosis of infection may be improved by
use of the polymerase chain reaction and by serology using a recombinant antigen,
K39. The therapeutic choice in visceral leishmaniasis is aided by recent studies
of the lipid-associated amphotericin B drugs and aminosidine (paromomycin).
Unfortunately, interferon-gamma, allopurinol, and topical aminosidine are all
less effective treatments than was originally thought.
PMID- 17033420
TI - Advances in schistosomiasis research.
AB - This review reports on recent developments in the areas of diagnosis,
chemotherapy and pathology, where female genital schistosomiasis was recently
identified as a common cause of morbidity in Schistosoma haematobium-endemic
areas. As a profound understanding of processes underlying resistance and
susceptibility to infection as well as pathology is central to schistosomiasis
control, detailed immunological studies of immunity and granuloma formation
dominate the discussion. Studies on host genetics, on T-helper cell type 1 or 2
cytokines as well as on cell types influencing immunity and granuloma formation
have provided precise information that could be of relevance not only to helminth
but also to microbial infections involving granulomatous reactions.
PMID- 17033421
TI - Tropical viral infections.
AB - This section should be of particular interest to the travel medicine physician as
it reports many new manifestations of exotic viral infections, both in terms of
new clinical expression or extension to new geographical territory. Included are
descriptions of improved diagnostic methodologies for arboviral diseases, a
discussion of safety issues involving a licensed travel medicine vaccine and a
randomized placebo-controlled trial of a drug widely prescribed to reduce
vascular permeability in dengue hemorrhagic fever.
PMID- 17033422
TI - Molecular and therapeutic advances in the management of chronic hepatitis B and
C.
AB - Three hundred million individuals worldwide have persistent hepatitis B virus
infection with 1-2 million hepatitis B virus-associated deaths per year, and an
estimated 1% of the world's population are infected with hepatitis C virus.
Recent advances in molecular biology and host responses have led to an increased
understanding of hepatitis B and C virus disease and new potential targets for
therapy.
PMID- 17033423
TI - Viral gastroenteritis.
AB - There are many viruses infecting the human gut: some are found to cause acute
gastroenteritis regularly (although not always) like rotaviruses, enteric
adenoviruses, small round structured viruses and astroviruses; others enter the
host via the gut and most often cause systemic infection (entero-viruses,
parvoviruses); and others are not regularly associated with human disease
(reoviruses, viruses of the Coronaviridae family). The human gut can also be
infected directly by HIV and, as a consequence of immuno-suppression, by viruses
of the Herpesviridae family. Most remarkable during the last one to two years
were the following results: increasing evidence that a tetravalent rhesus
rotavirus-based vaccine can prevent severe disease after natural human rotavirus
infection bringing this vaccine candidate close to approval by the Food and Drug
Administration, USA; better, although not complete, understanding of correlates
of protection from rotavirus infection; and fuller comprehension of the genomic
and antigenic diversity of viruses of the Caliciviridae family infecting man.
There is still no proficient tissue culture system for the human small round
structured viruses, hindering the acquisition of basic knowledge of the
replication of these viruses in the human gut. Except against rotaviruses, there
are no vaccine candidates against human enteric viruses.
PMID- 17033424
TI - Bacterial infections of the gut (excluding enteric fever).
AB - Bacterial enteric infections are still a major cause of morbidity and mortality,
and many challenges lie ahead in understanding and managing these conditions.
Clostridium difficile remains the most important nosocomial infection. Antibiotic
resistance makes the treatment of shigella infections increasingly difficult.
Molecular and cellular techniques are, however, rapidly expanding our
understanding of the complexity of the pathogenesis of established and newly
recognized pathogens.
PMID- 17033425
TI - Epidemiology, diagnosis and treatment of enteric fever.
AB - Enteric fever continues to be a common and serious problem worldwide, and the
need for reliable and cheap alternatives to culture methods for diagnosis
remains. Epidemics of different strains may coexist in the same geographical area
and the rapid emergence of resistance to fluoroquinolones, independent of plasmid
mediated multidrug resistance, means that alternative drugs for chemotherapy are
also needed.
PMID- 17033426
TI - Vaccination against bacterial gut infections.
AB - Recent developments in the field of vaccination against gut-borne bacterial
illness are reviewed, including the major pathogens such as salmonella, shigella,
cholera and Escherichia coli. The approaches covered range from immunization with
killed and live attenuated organisms to genetically detoxified toxin molecules
and DNA vaccination and transgenic foods. Both homologous and heterologous
responses to various organisms and vector technologies are discussed in murine,
bovine and human models, and conclusions are drawn regarding their potential use
in the development of safe, effective and economically viable vaccines.
PMID- 17033427
TI - Parasitic gut infections.
AB - Emerging spore-forming protozoa such as cryptosporidia and microsporidia are
becoming major public health problems in developing countries as well as in the
developed world. They are a new addition to an already long list of intestinal
parasites, but their diagnosis is much more difficult than for well-known
protozoa and helminths. Fortunately, enzyme immunoassay and polymerase chain
reaction techniques are becoming available not only for the detection of
Cryptosporidium parvum and the microsporidia, but also for Entamoeba histolytica
and Giardia lamblia. These assays are not only increasing the sensitivity of
detection but are also allowing, for the first time, species differentiation such
as Entamoeba histolytica/dispar or Encephalitozoon intestinalis/Enterocytozoon
bieneusi.
PMID- 17033430
TI - Transjugular intrahepatic portosystemic stent-shunt: technical factors and new
developments.
AB - The introduction of expandable metal stents in the mid 1980s led to the
development of transjugular intrahepatic portosystemic stent-shunt (TIPSS) as we
know it today. Short-lived detrimental effects on the hyperdynamic circulation in
cirrhosis accompany the acute reduction in portal pressure following TIPSS
creation. Caution is needed in patients with cardiac dysfunction or pulmonary
hypertension. With increasing expertise and careful patient selection, fatal
procedural complications are rare and TIPSS can even be safely used as a bridge
to liver transplantation. Shunt insufficiency and hepatic encephalopathy are more
common following TIPSS. Currently, however, novel approaches to tackling both
these limitations exist. These include the combination of uncovered TIPSS with
variceal band ligation, and the introduction of polytetrafluoroethylene covered
stents. Despite the lack of controlled studies, covered stents are now widely
used and have the potential to drastically reduce shunt insufficiency, the need
for long-term shunt surveillance and even hepatic encephalopathy.
PMID- 17033431
TI - The use of transjugular intrahepatic portosystemic stent shunt in the management
of acute oesophageal variceal haemorrhage.
AB - Variceal haemorrhage is a common and serious complication of portal hypertension.
Endoscopic therapy is successful in the majority in controlling bleeding but in
those who continue to bleed transjugular intrahepatic portosystemic stent shunt
is highly effective in achieving haemostasis, although the evidence base that
this is associated with improved survival is limited. This review discusses
initial management and then the particular role of transjugular intrahepatic
portosystemic stent shunt. A management algorithm is proposed. The timing of
intervention is emphasized and the importance of admission to specialized
centres. Regional protocols are probably essential for the latter to be organized
effectively.
PMID- 17033432
TI - Transjugular intrahepatic portosystemic shunt in the management of ascites and
hepatorenal syndrome.
AB - Ascites is the most common complication of liver cirrhosis and when it develops
mortality is 50% at 5 years, apart from liver transplantation. Large volume
paracentesis has been the only option for ascites refractory to medical
treatment. The role of transjugular intrahepatic portosystemic shunt in the
management of diuretic-resistant ascites has been evaluated in many cohort
studies and five randomized trials up to now, clearly showing improvement in
natriuresis and clinical efficacy. It, however, remains unclear how transjugular
intrahepatic portosystemic shunt affects survival and quality of life, because
hospital admissions owing to worsening encephalopathy may counterbalance the
reduced need of paracentesis. What is clear is that the patient selection is
critical. About 30% of patients with ascites develop hepatorenal syndrome at 5
years, leading to high mortality in its severe and progressive form. As its main
pathogenetic factor is derangement of circulatory function owing to portal
hypertension, these patients may benefit from transjugular intrahepatic
portosystemic shunt, but this has been shown only in small series, in which
mortality remains very high, owing to the underlying poor liver function.
PMID- 17033433
TI - Transjugular intrahepatic portosystemic shunt in the management of Budd Chiari
syndrome.
AB - Budd Chiari syndrome presents with a wide range of severity and duration of
symptoms. Transjugular intrahepatic portosystemic shunt has been used to treat
selected Budd Chiari syndrome patients for several years. The technique of
transjugular intrahepatic portosystemic shunt may be more challenging than in
cirrhosis because of hepatic vein occlusion. Covered transjugular intrahepatic
portosystemic shunt stents have reduced the requirement for follow-up
interventions. Transjugular intrahepatic portosystemic shunt has been a
successful bridge to liver transplant for Budd Chiari syndrome but is the
definitive treatment in many cases. Patient selection is important to determine
who will benefit from transjugular intrahepatic portosystemic shunt or other
treatments such as hepatic vein recanalization or liver transplant.
PMID- 17033434
TI - Transjugular intrahepatic portosystemic stent-shunt in the management of gastric
and ectopic varices.
AB - Uncertainty exists about the ideal therapy for gastric and ectopic varices owing
to relatively few controlled studies. Endoscopic therapy with tissue adhesives
and thrombin appear promising. Transjugular intrahepatic portosystemic stent
shunt has a role in patients with refractory gastric variceal bleeding in the
presence of a patent portal vein. The addition of coil embolization may be
particularly useful for ectopic varices, as these can continue to bleed despite
successful portal pressure reduction. The high efficacy of transjugular
intrahepatic portosystemic stent-shunt has to be balanced against the potential
for increased encephalopathy. Balloon occluded retrograde transvenous
obliteration is a recent technique for patients with gastro-renal shunts and
large gastric varices. Early results are promising, and balloon occluded
retrograde transvenous obliteration may be valuable in patients who bleed at
lower portal pressures, in the encephalopathic patient, or where the portal vein
is not patent. Its use may be limited by availability or lack of technical
expertise, and caution is required in patients with large oesophageal varices.
PMID- 17033435
TI - Miscellaneous indications for transjugular intrahepatic portosystemic stent
shunt.
AB - This review will discuss the use of transjugular intrahepatic portosystemic stent
shunt in a number of relatively uncommon clinical situations. In particular, we
will focus our paper on the use of transjugular intrahepatic portosystemic stent
shunt for hepatic hydrothorax, hepatopulmonary syndrome, veno-occlusive disease,
portal hypertensive gastropathy and gastric antral vascular ectasia, before
surgery and after liver transplantation.
PMID- 17033436
TI - Transjugular intrahepatic portosystemic shunt in the prevention of rebleeding in
oesophageal varices.
AB - Variceal bleeding is a common complication of cirrhosis and has a high in-patient
mortality (30-50%). Rebleeding is a major cause of death and occurs in 35% of
patients at 6 weeks after the initial bleeding episode and 75% at 1 year.
Therefore, strategies that improve survival by preventing rebleeding in the early
period are crucial to improve long-term survival. This review concentrates on the
evidence for transjugular intrahepatic portosystemic shunt in the prevention of
rebleeding. Transjugular intrahepatic portosystemic shunt in comparison with
endoscopic and pharmacological therapies is clearly superior at reducing the rate
of rebleeding in those patients who had an oesophageal variceal haemorrhage. It,
however, does not improve mortality and is associated with a greater risk of
encephalopathy and is more costly than endoscopic procedures. It is therefore
generally used when endoscopic therapy has failed but may be useful in patients
who would tolerate a rebleed poorly such as Child's C patients. Randomized
controlled trials are required to evaluate the role of polytetrafluoroethylene
shunts in the prevention of rebleeding as their improved patency and suggested
reduced incidence of encephalopathy make them a very attractive potential
treatment for rebleeding.
PMID- 17033437
TI - Adult population screening for coeliac disease: comparison of tissue
transglutaminase antibody and anti-endomysial antibody tests.
AB - Serological screening tests for coeliac disease have significantly advanced the
diagnosis of this condition. The very high specificity (almost 100%) of anti
endomysial antibody detection has been repeatedly confirmed, whereas a lower
specificity (90-95%) is found with anti-tissue transglutaminase antibody assays.
In the study by Malekzadeh and colleagues, a group of study participants were
identified with raised anti-tissue transglutaminase antibodies, but the
endomysial antibody test was negative in 86%. Although many of these participants
were found to have raised intra-epithelial lymphocytes in their small intestinal
mucosa, there is currently insufficient evidence to confidently diagnose gluten
sensitive disease in these patients. Hence, their report that a minimum
prevalence of 1:104 of gluten sensitivity is found in the general population of
Iran is likely to be an over-estimate and requires confirmation.
PMID- 17033438
TI - Self-expanding stents in oesophageal cancer.
AB - The main therapeutic concern in patients with inoperable oesophageal cancer is
palliation of dysphagia. Self-expandable metal stents are widely used because
they are safer than conventional plastic stents, offer rapid relief from
dysphagia and may seal off tracheo-oesophageal fistulae. Self-expanding metal
stents, particularly when uncovered, are, however, associated with the
disadvantage of tumour ingrowth. Self-expandable plastic stents are entirely
covered and easy to reposition in case of migration and usually induce less
inflammatory proliferation at their flanges when compared with metal stents. The
major disadvantage of the current version of plastic stents is the large diameter
and stiffness of the stent delivery system when compared with metal stents.
Therefore, plastic stents are more difficult to place in patients with angulated
strictures or with tumours located in the cervical oesophagus near the upper
sphincter.
PMID- 17033439
TI - Screening of the adult population in Iran for coeliac disease: comparison of the
tissue-transglutaminase antibody and anti-endomysial antibody tests.
AB - BACKGROUND AND AIMS: Population-based studies for the prevalence of coeliac
disease (CD) in west-Asian countries are scarce. We aimed to determine the
prevalence of gluten-sensitive enteropathy (GSE) in the general population of
northern and southern Iran, and evaluate the sensitivity and specificity of the
anti-endomysial antibody (EMA) immunofluorescent test and the enzyme-linked
immunosorbent assay-based test for determination of the IgA anti-tissue
transglutaminase antibody (tTG-Ab) using the human recombinant transglutaminase
antigen for the detection of CD in screening the asymptomatic adult population.
MATERIAL AND METHODS: Using a stratified random sampling method we enrolled a
total of 2799 individuals (1438 from Sari and 1361 from Kerman). The mean age was
33.7 years (range 18-66), with 1398 men. IgA anti-tissue transglutaminase (tTG)
and IgA anti-EMA were determined in the serum of all subjects. Those participants
with a positive serology for any of the two tests underwent small intestinal
biopsy, and were classified according to revised Marsh criteria histologically. A
diagnosis of GSE was based on positive serology and a compatible
histopathological finding. The maximum likelihood latent class model was used to
estimate the sensitivity and specificity of the two tests. RESULTS: Twenty-nine
cases showed positive IgA tTG-Ab (15 men and 14 women, mean age 35.4 years, range
18-59), whereas only five were simultaneously positive for EMA. Except for two
subjects with normal small bowel histology (Marsh 0), all other subjects were
found to have biopsy findings compatible with GSE: 18 Marsh I, five Marsh II,
three Marsh IIIa and one Marsh IIIc lesions. he prevalence of GSE was 0.96% or
1:104. The sensitivity and specificity of the human-recombinant IgA tTG-Ab assay
were 100 and 99%, respectively, whereas the results for IgA EMA were 19 and 100%,
respectively. The IgA EMA was positive in cases with advanced mucosal lesions of
the small bowel. The mean serum value of IgA tTG-Ab was higher in patients with
severe enteropathy compared with those showing slight mucosal changes (P<0.05).
CONCLUSION: The minimum prevalence of gluten sensitivity among the general
population of northern and southern Iran is 1:104. The best screening test for
the detection of GSE in the general population is IgA tTG-Ab.
PMID- 17033440
TI - Consumption of gluten-free products: should the threshold value for trace amounts
of gluten be at 20, 100 or 200 p.p.m.?
AB - OBJECTIVE: The threshold of gluten contamination in gluten-free products of both
dietary and normal consumption is under debate. The objective of this study was
to gather information on consumption of gluten-free products intended for dietary
use of people under a gluten-free diet. This information is essential to
ascertain the exposure of coeliac patients to gluten through their diet and
deduce the maximum gluten content that these products should contain to guarantee
a safe diet. METHODS: A diet diary of consumption of gluten-free products
intended for dietary use was distributed to the coeliac societies of two typical
Mediterranean countries (Italy and Spain) and two Northern countries (Norway and
Germany). The diet diary included a self-weigh table of the selected food items
and a 10-day consumption table. Results were reported in percentiles as
distributions were clearly right skewed. RESULTS: The respondents included in the
study accounted for 1359 in Italy, 273 in Spain, 226 in Norway and 56 in Germany.
Gluten-free products intended for dietary use contributed significantly to the
diet of coeliac patients in Italy, Germany and Norway and to a lesser degree in
Spain. The most consumed gluten-free product in all countries was bread, and it
was double consumed in the Northern countries (P<0.001). Mediterranean countries
showed consumption of a wider variety of gluten-free foods and pasta was eaten to
a large degree in Italy. CONCLUSIONS: The differences between Northern and
Mediterranean countries were not in the total amount of gluten-free products but
in the type of products consumed. The observed daily consumption of gluten-free
products results in the exposure to rather large amounts of gluten, thus the
limit of 200 p.p.m. should be revised. A limit of 20 p.p.m. for products
naturally gluten-free and of 100 p.p.m. for products rendered gluten-free is
proposed to guarantee a safe diet and to enable coeliac patients to make an
informed choice. These limits should be revised as new data become available.
PMID- 17033441
TI - Palliative treatment of esophageal carcinoma with self-expanding plastic stents:
a report on 69 cases.
AB - OBJECTIVES: The use of self-expandable plastic stents has offered a reasonable
alternative of self-expandable metal stents in palliative treatment of esophageal
malignancies, in the recent years. Studies and clinical data on the use of self
expandable plastic stents in esophageal cancer are, however, available in a very
limited number. Here, we present the results of our 3-year study designed to
evaluate the efficacy of self-expandable plastic stents in palliation of advanced
esophageal carcinoma. PATIENTS AND METHODS: Between January 2001 and February
2004, 69 patients with advanced nonoperable esophageal cancer were enrolled in
the study and followed up until their death, after insertion of Polyflex self
expandable plastic stents. Dysphagia scores, Karnofsky indices and body weights
were determined and compared in order to evaluate the effect of the stent
insertion on general status and well-being of the patients. RESULTS: Insertion of
Polyflex self-expandable plastic stents and covered self-expandable metal stents
was performed in 66 cases and in eight cases, respectively; in certain patients,
owing to complications, more than one stent had to be inserted. In all cases, the
insertion of stents has been performed without major complication and it has led
to an instant improvement in swallowing and dysphagia scores. The rates of
tumoral overgrowth and of stent migration were low. The mean follow-up time of
our patients was 129 days (10-312 days). CONCLUSION: In concordance with previous
studies, according to our results, the use of self-expandable plastic stents in
palliation of esophageal cancer seems to be safe and effective in improving the
quality of life of these patients.
PMID- 17033442
TI - Surface area: a better predictor of disease severity than the height and volume
of the barium column in patients with primary achalasia.
AB - OBJECTIVE: Subjective assessment of primary achalasia is not accurate. We aimed
to study the utility of surface area of barium retention in the objective
assessment of these patients. METHODS: Subjective and objective esophageal
functions of 99 patients with primary achalasia were evaluated initially and 43
of them were reevaluated 1 month after balloon dilation. RESULTS: Before
dilation: Ninety-nine patients were enrolled. Forty-one of them were male. The
mean age was 37.5+/-15.3 years. The mean score, resting lower esophageal
sphincter pressure, height, surface and volume of barium retention at 5 min were
8.03+/-3.1, 59.1+/-20 mmHg, 9.9+/-4.9 cm, and 23.6+/-13.9 cm and 53.2+/-47.7 cm,
respectively. Surface area at 5 min had best correlation and predictive value for
resting lower esophageal sphincter pressure. After dilation: Forty-three of 99
patients were reevaluated after balloon dilation. The mean age was 36.8+/-13.6
years. Seventeen of them were male. Mean score, resting lower esophageal
sphincter pressure, height, surface area and volume of barium retention at 5 min
dropped significantly after dilation. Surface area at 5 min had best correlation
and predictive value for lower esophageal sphincter pressure. CONCLUSIONS:
Surface area of barium retention at 5 min is an accurate objective tool to assess
patients with primary achalasia. It is cheap and easy to perform; therefore, it
could be used more frequently in postdilation follow-up.
PMID- 17033443
TI - The pathogenesis of idiopathic megacolon.
AB - BACKGROUND: Even today, the pathogenesis of idiopathic megacolon is still a
subject of controversy. Anomalies of the gastrointestinal autonomous nervous
system or of the smooth muscle of the muscularis propria are being considered.
METHODS: Sixty-three idiopathic megacolon resections between 1997 and June 2004
were investigated. The native specimens were coiled caudo-cranially and cryostat
cut. Connective tissue was stained with picric acid/Sirius red after Delauney
fixation. Immunohistochemistry was performed for collagen types I, II, III and
IV, as well as smooth muscle actin, vimentin, desmin fibronectin and CD117 for
interstitial cells of Cajal. The enteric nervous system was examined by enzyme
histochemistry for acetylcholine-esterase, lactate dehydrogenase, succinic
dehydrogenase and nitroxide synthase. RESULTS: Histologically, idiopathic
megacolon was characterized by a total atrophy of the collagenous tendinous
connective tissue membrane of the myenteric plexus and the tendinous collagen
fibre net of the muscularis propria. Immunohistochemically, mainly collagen type
III was missing in the muscularis propria. Interestingly, the incidence of
idiopathic megacolon in those of the female sex was seven times more frequent
than in the male sex. The myenteric plexus was normal in the majority of
patients. Interstitial cells of Cajal, collagen II and IV, as well as smooth
muscle actin, desmin and fibronectin showed no consistent alteration. CONCLUSION:
A normally structured tendinous fibre net of muscularis propria is an essential
prerequisite for effective gut peristalsis. Atrophy of the tendinous fibre net
abolishes peristalsis and allows for unlimited distension of the colon. A
diagnosis of idiopathic megacolon can reliably be made on a collagen stain. The
normal findings of myenteric plexus support the hypothesis that a primary
metabolic defect of muscularis propria may be the underlying cause of idiopathic
megacolon.
PMID- 17033445
TI - Changing serological status and low vaccination-induced protection rates against
hepatitis B characterize chronic hepatitis C virus-infected injecting drug users
in Greece: need for immunization policy.
AB - OBJECTIVE: To evaluate the serological status of hepatitis B virus infection
among Greek injecting drug users with chronic hepatitis C virus infection; to
correlate hepatitis B virus infection status with the possible time of infection
and the principal genotype of hepatitis C virus infection. METHODS: Two hundred
and thirty consecutive injecting drug users with chronic hepatitis C virus
infection were evaluated for serological markers of hepatitis B virus infection.
One hundred and three of them (44.8%) reported intravenous drug use beginning
before 1992 (group A) and 127/230 (55.2%) after 1992 (group B). Statistical
analysis of data was based on Student's t-test and chi analyses. RESULTS: Eighty
five of 103 patients from group A (82.5%) and 28/127 (22%) from group B had
serological markers of previous hepatitis B virus infection (P<0.001). Eleven
patients from group A (10.6%) and 78 (61.4%) from group B were seronegative for
all hepatitis B virus markers (P<0.001). Only 3.8% (4/103) of group A patients
and 16.5% (21/127) of group B had vaccination-induced protective antibody levels
(anti-HBs) against hepatitis B (P=0.02). The majority of patients were infected
with hepatitis C virus genotype-3 (64.7% from group A vs 56.7% from group B,
P=0.42). The percentages of patients infected with genotype-1 were also
comparable in both groups (15.5% from group A vs 30.8% from group B, P=0.09). A
significantly higher percentage of group A patients were infected with genotype-4
(19.7%) than those in group B (4.9%, P=0.02). CONCLUSION: The serological profile
of hepatitis B virus infection among Greek hepatitis C virus-infected injecting
drug users is changing. The proportion of successfully vaccinated hepatitis B
virus injecting drug users, although significantly higher than the previous
decades, is still relatively low. Vaccination policy in this high-risk group for
viral hepatitis is urgently needed.
PMID- 17033444
TI - The complementary Erlangen active simulator for interventional endoscopy training
is superior to solely clinical education in endoscopic hemostasis--the French
training project: a prospective trial.
AB - BACKGROUND: The Erlangen Active Simulator for Interventional Endoscopy (EASIE)
using ex-vivo porcine organs was introduced in 1997. The present study should
analyze whether repeated EASIE simulator training in endoscopic hemostasis led to
superior performance compared with a traditionally educated group. The results
were compared with a similar project in New York. METHODS: Thirty-five French GI
fellows were enrolled. Baseline skills evaluation was performed in four
disciplines (manual skills, injection/coagulation, clip application and variceal
ligation) using the compactEASIE-simulator equipped with an upper
gastrointestinal organ package for bleeding simulation. The same, translated
evaluation forms (from the prior New York project) were used. Subsequently,
fellows were randomized into group A (n=17, only clinical education) and group B
(n=18, additional three simulator trainings). Group B was trained the next day
and after 4 and 7 months by experts of the French Society of Gastrointestinal
Endoscopy. Both groups performed routine and emergency endoscopies at their home
hospitals during the study period. Both groups were re-evaluated blindly after 9
months. RESULTS: The learning curve for group B showed a significant improvement
in all disciplines (P<0.004) whereas group A improved significantly in only two
of four disciplines at blinded final evaluation (manual skills P=0.02,
injection/coagulation P=0.013). The direct comparison of groups B and A at
blinded final evaluation showed significantly superior ratings for group B in all
disciplines (P<0.006) and significantly shorter performance times in two
disciplines (P=0.016 each). The comparison with the similar 'New York project'
revealed that preexisting differences in skills were adjusted by the training.
CONCLUSION: Complementary trainings (three workshops in 7 months) in endoscopic
hemostasis using the compactEASIE improved skills compared with a solely clinical
education. The results of the 'New York project' were confirmed and benefits were
independent from the medical educational system.
PMID- 17033446
TI - Anastrozole-induced hepatotoxicity.
AB - We present a case of hepatotoxicity induced by an aromatase-inhibiting hormonal
antineoplastic drug (anastrazol) in an elderly woman. This is the first reported
case in the literature.
PMID- 17033447
TI - Imatinib mesylate-induced acute hepatitis with autoimmune features.
AB - Autoimmune hepatitis is a disorder of unknown aetiology. Imatinib belongs to a
new class of anticancer agents with high selectivity toward a specific molecular
target. Its main indications are chronic myeloid leukaemia and gastrointestinal
tumours. We report here, for the first time to our knowledge, imatinib mesylate
induced hepatitis with autoimmune features.
PMID- 17033448
TI - Olive oil for symptomatic relief of duodeno-gastro-oesophageal reflux after
gastrectomy.
PMID- 17033450
TI - Introduction of the 29th Lauriston S. Taylor Lecturer, John B. Little.
PMID- 17033451
TI - Lauriston S. Taylor lecture: nontargeted effects of radiation: implications for
low-dose exposures.
AB - Traditional thinking has been that the biological effects of ionizing radiation
occur in irradiated cells as a consequence of the DNA damage they incur. This
implies that (1) biological effects occur only in irradiated cells, (2) radiation
traversal through the nucleus of the cell is a prerequisite to produce a
biological response, and (3) DNA is the target molecule in the cell. Evidence has
been emerging, however, for non-DNA targeted effects of radiation; that is,
effects including mutations, chromosomal aberrations, and changes in gene
expression that occur in cells that in themselves receive no radiation exposure.
Two of these phenomena will be described in this paper. The first is radiation
induced genomic instability whereby biological effects, including elevated
frequencies of mutations and chromosomal aberrations, arise in the distant
descendants of irradiated cells. The second phenomenon has been termed the
"bystander effect," whereby in a mixed population of irradiated and nonirradiated
cells, biological effects arise in those cells that receive no radiation
exposure. The damage signals are transmitted from cell to cell through gap
junction channels, and the genetic effects observed in bystander cells appear to
result from an upregulation of oxidative stress. The possible influence of these
nontargeted effects of radiation on the response to low-dose exposures is
discussed.
PMID- 17033452
TI - Managing the disposition of low-activity radioactive materials. Proceedings of
the 41st Annual Meeting of the National Council on Radiation Protection and
Measurements. 2005. Bethesda, Maryland, USA.
PMID- 17033453
TI - Warren K. Sinclair keynote address: contemporary issues in risk-informed decision
making on the disposition of radioactive waste.
AB - A consistent and transparent risk-informed approach to managing nuclear waste is
plagued with different regulators, different rules and regulations for different
waste types, different compliance requirements, and indecisions about
probabilistic vs. deterministic models. Low-activity waste management is
particularly void of a path forward with respect to being risk-informed. Risk
assessment is not referenced in the statutes on low-activity waste even though
both the U.S. Environmental Protection Agency and U.S. Nuclear Regulatory
Commission (U.S. NRC) have policies to apply consistent risk management
approaches to all of their programs. The U.S. NRC has developed guidance on the
preparation of probabilistic performance assessments for low-activity waste
facilities, but there have been no serious takers and a lack of initiative on the
part of licensees. Thus, little to no experience exists on risk-informing low
activity waste. The missed opportunities include establishing a risk basis that
would allow for simpler, safer, and much less costly alternatives for low
activity waste disposal while enabling society to have the full benefit of
radiation technologies. There is hope that congressional action or regulatory
rule making will address some of these issues with the result being the adoption
of a more general and unified approach to risk-informed regulation of all types
of waste. Just as much of the initiative for risk-informed nuclear power came
from industry, it must also be the case for nuclear waste. A start would be the
adoption of a basic framework of risk assessment in waste management applicable
to all types of waste--radioactive and nonradioactive. The "set of triplets" risk
assessment framework that is applicable to any kind of risk is an established
alternative. It is believed that such a framework with the support of a
regulatory structure made compatible through appropriate rulemaking or
congressional action, and the experience of the probabilistic performance
assessments for the Waste Isolation Pilot Plant and the proposed Yucca Mountain
high-level waste repository, could result in the right path forward for the
regulation and management of low-activity waste.
PMID- 17033454
TI - Improving the regulation and management of low-activity radioactive wastes.
AB - This paper summarizes the first phase of a study in progress by a committee of
the National Research Council's Board on Radioactive Waste Management. The Board
initiated the study after observing that statutes and regulations administered by
the federal and state agencies that control low-activity radioactive wastes have
developed as a patchwork over almost 60 y. These controls usually reflect the
enterprise or process that produced the waste rather than the waste's
radiological hazard. Inconsistencies in the regulatory patchwork or its
application may have led to overly restrictive controls for some low-activity
wastes while others were neglected in comparison. In the first phase of this
study, the committee reviewed current low-activity waste inventories,
regulations, and management practices. This led the committee to develop five
categories that encompass the spectrum of low-activity wastes and serve to
illustrate gaps and inconsistencies in current regulations and management
practices. The committee completed its first phase with four findings that will
lead into the final phase of the study. This paper is excerpted from the
committee's interim report that was issued in October 2003.
PMID- 17033455
TI - Risk-informed radioactive waste classification and reclassification.
AB - Radioactive waste classification systems have been developed to allow wastes
having similar hazards to be grouped for purposes of storage, treatment,
packaging, transportation, and/or disposal. As recommended in the National
Council on Radiation Protection and Measurements' Report No. 139, Risk-Based
Classification of Radioactive and Hazardous Chemical Wastes, a preferred
classification system would be based primarily on the health risks to the public
that arise from waste disposal and secondarily on other attributes such as the
near-term practicalities of managing a waste, i.e., the waste classification
system would be risk informed. The current U.S. radioactive waste classification
system is not risk informed because key definitions--especially that of high
level waste--are based on the source of the waste instead of its inherent
characteristics related to risk. A second important reason for concluding the
existing U.S. radioactive waste classification system is not risk informed is
there are no general principles or provisions for exempting materials from being
classified as radioactive waste which would then allow management without regard
to its radioactivity. This paper elaborates the current system for classifying
and reclassifying radioactive wastes in the United States, analyzes the extent to
which the system is risk informed and the ramifications of its not being so, and
provides observations on potential future direction of efforts to address
shortcomings in the U.S. radioactive waste classification system as of 2004.
PMID- 17033456
TI - Managing the disposition of potentially radioactive scrap metal.
AB - In 2002, the National Council on Radiation Protection and Measurements (NCRP)
issued Report No. 141, Managing Potentially Radioactive Scrap Metal. The report
evaluates management policy and related issues regarding scrap metal generated in
regulated facilities that have been under radiological control or have
radiological concerns. It has been estimated that more than 9 million metric tons
of scrap metal of all types that have been associated with the production or use
of radioactive materials will be generated during the coming decades at various
facilities across the United States. Currently, disposition of such metal has
encountered particular obstacles, primarily because of the lack of a consistent
disposition policy, systematic regulatory provisions, and, above all, public
understanding. Without clarity in the regulatory passage, much of the scrap
metal, including metal that has not been contaminated, could be mischaracterized
as low-level radioactive waste, resulting in a costly disposition operation. NCRP
Report No. 141 identifies this general category of metal as "potentially
radioactive scrap metal" (PRSM) and discusses the viable disposition options for
facilitating its management. Because much of the PRSM has been found to contain
very low residual radioactivity or even none at all, one consideration is to
release such metal outside of the radiological control framework. This would
require the development and implementation of a set of strict release standards
in the United States that would necessarily be risk-based and supported by a
comprehensive management scheme. Developing a policy of this kind, however, would
entail the resolution of many issues, not the least of which would be public
acceptance, including that of the metal industry, of the possible recycling of
PRSM in the general commerce.
PMID- 17033457
TI - International standards related to the classification and deregulation of
radioactive waste.
AB - Although solid radioactive waste management is mainly a national concern, there
are some aspects that have international implications. One important example is
the decommissioning of nuclear facilities, which results in the release of
materials that could be reused and recycled. It is possible that these materials
could enter international trade, especially if the material is a metal. It is
clearly desirable, therefore, to have appropriate international standards to help
regulate trade. This paper describes recent international developments relating
to the establishment of radiological criteria for the release of materials from
regulatory control (clearance). There have already been some experiences of
clearance and the transfer of recycled materials within Europe, and this paper
reviews that experience. It also discusses recent developments in relation to the
international classification of radioactive waste.
PMID- 17033458
TI - The Spanish Protocol for radiological surveillance of metal recycling: a
collaboration of government and industry.
AB - The presence of radioactive materials in scrap metal has been detected relatively
often in recent years. As a result of an accidental melting of a 137Cs source in
a Spanish steel mill (Acerinox) in 1998, the national authorities, the involved
private companies, and the main trade unions drafted a protocol for prevention of
and responding to such events ("Spanish Protocol"). The Protocol was signed in
1999. The number of subscribing companies is 90. The Protocol is a voluntary
agreement defining the radiological surveillance of scrap metal and its products
and the duties and rights of the signatories. From the effective date of the
Protocol to December 2004, 461 pieces of ferric scrap were detected including
sources of radiation and contaminated metal. Four melting incidents have happened
in different companies.
PMID- 17033459
TI - An industry perspective on commercial radioactive waste disposal conditions and
trends.
AB - The United States is presently served by Class-A, -B and -C low-level radioactive
waste and naturally-occurring and accelerator-produced radioactive material
disposal sites in Washington and South Carolina; a Class-A and mixed waste
disposal site in Utah that also accepts naturally-occurring radioactive material;
and hazardous and solid waste facilities and uranium mill tailings sites that
accept certain radioactive materials on a site-specific basis. The Washington
site only accepts low-level radioactive waste from 11 western states due to
interstate Compact restrictions on waste importation. The South Carolina site
will be subject to geographic service area restrictions beginning 1 July 2008,
after which only three states will have continued access. The Utah site dominates
the commercial Class-A and mixed waste disposal market due to generally lower
state fees than apply in South Carolina. To expand existing commercial services,
an existing hazardous waste site in western Texas is seeking a Class-A, -B and -C
and mixed waste disposal license. With that exception, no new Compact facilities
are proposed. This fluid, uncertain situation has inspired national level
rulemaking initiatives and policy studies, as well as alternative disposal
practices for certain low-activity materials.
PMID- 17033460
TI - Scrap metals industry perspective on radioactive materials.
AB - With more than 80 reported/confirmed accidental melts worldwide since 1983 and
still counting, potential contamination by radioactive materials remains as a
major concern among recycled scrap and steel companies. Some of these events were
catastrophic and have cost the industry millions of dollars in business and, at
the same time, resulted in declining consumer confidence. It is also known that
more events with confirmed radioactive contamination have occurred that involve
mining of old steel slag and skull dumps. Consequently, the steel industry has
since undergone massive changes that incurred unprecedented expenses through the
installation of radiation monitoring systems in hopes of preventing another
accidental melt. Despite such extraordinary efforts, accidental melts continue to
occur and plague the industry. One recent reported/confirmed event occurred in
the Republic of China in 2004, causing the usual lengthy shutdown for expensive
decontamination efforts before the steel mill could resume operations. With this
perspective in mind, the metal industry has a long-standing opposition to the
release of radioactive materials of any kind to commerce for fear of
contamination and the potential consequences.
PMID- 17033461
TI - A radioactive metal processing industry perspective source.
AB - The current U.S. economic environment for the disposition of radioactive waste,
including very-low-activity metals, is currently experiencing relatively low
radioactive disposal costs and readily available disposal space. Despite the
recent market increase in demand for recycled scrap metal commodities, there is
still little change in the behavior of the nuclear industry (including
radioactive waste processors and radioactive scrap metal recyclers) to pursue the
recycling of potentially contaminated scrap metal. The relatively low cost of
traditional radioactive waste disposal combined with the perceived risks
associated with recycling of previously contaminated metals means that most U.S.
radioactive facility managers and stakeholders will elect not to recycle. Current
technology exists and precedence has been set for prescreening (by means of bulk
radioactive assay techniques) scrap metal that is not contaminated and diverting
it to industrial landfills for disposal. Other processes also allow some
radiologically contaminated metals to be melted and recast into products with
low, but acceptable, activity levels for restricted use in the nuclear industry.
A new concept is being considered that would create a centralized licensed
facility for the process and disposition of "very-low-activity" metals for
"directed first use." The advantages to this type of approach would include a
standardized method for licensing the clearance process.
PMID- 17033462
TI - Low-activity radioactive materials management at the U.S. Department of Energy.
AB - The U.S. Department of Energy (U.S. DOE) is making significant progress with the
cleanup of its legacy radioactively-contaminated facilities and sites left from
research and development and production of nuclear materials and weapons. Sites
like Rocky Flats, Battelle Columbus Laboratories, Fernald, Mound, Brookhaven
National Laboratory, Hanford, and Oak Ridge are faced daily with decisions
related to disposition of waste and radioactive material. One key to this success
is the disposition of waste arising from cleanup. Most of the generated waste
volume has very low levels of radioactive contamination. The waste includes
contaminated soil, debris from demolition, or scrap metal and equipment. The cost
of disposing of large volumes of waste can be prohibitive, so there is incentive
to find innovative ways to disposition wastes. This paper describes the current
status of policy development in this area, such as development of a draft
programmatic environmental impact statement and monitoring of related rulemaking
at the U.S. Nuclear Regulatory Commission. The paper also provides an overview of
draft U.S. DOE guidance on control and release of property with residual
radioactive material, and site-specific applications of DOE guidance.
PMID- 17033463
TI - Political life and half-life: the future formulation of nuclear waste public
policy in the United States.
AB - The United States continues to need forward-thinking and revised public policy to
assure safe nuclear waste disposal. Both the high- and low-level disposal plans
enacted by Congress in the 1980's have been frustrated by practical and political
interventions. In the interim, ad hoc solutions and temporary fixes have emerged
as de facto policy. Future statutory, regulatory, and administrative guidance
will likely be less bold, more narrowly focused, and adopted at lower levels of
government, more informally, in contrast to the top-down, statutory policies of
the 1980's.
PMID- 17033464
TI - An analysis of public-interest group positions on radiation protection.
AB - The history of radiation risk management is replete with contentious public
debate between public interest groups and the technical community of radiation
protection professionals. To promote a deeper understanding of this phenomenon,
this paper describes the rationales and values underlying public-interest group
positions in one radiation risk domain (low-level waste) and contrasts them with
those of the technical community. Public interest group objections to recycling
of radioactivity-contaminated materials and to discarding of other low-level
wastes are made on fairness, risk assessment, and energy-policy grounds. Concerns
about procedural fairness stem from the continuing use of top-down expert-driven,
rather than deliberative, systems for low-level waste policy-making. Concerns
about distributional fairness arise because the benefits and risks of alterative
low-level waste policies accrue to different stakeholders. Risk assessment is
faulted for failure to acknowledge hidden subjective assumptions (e.g., on
screening vigilance in materials recycling, on integrity of disposal facilities
in the far future). Skepticism of technological risk management arises from a
history peppered with unexpected untoward events that lay outside the design
bases of protection systems. Finally, public interest groups view low-level waste
issues as part of a larger debate on wise and legitimate energy policy, and are
reluctant to support measures that provide relief to a nuclear industry that, in
their view, established itself outside the democratic process.
PMID- 17033465
TI - Policy development from the industry perspective.
AB - The responsibility and burden for implementation of any option for the
disposition of low-activity radioactive waste will primarily reside with the
industries that generate the waste and those that provide the necessary waste
management and disposal services. Unfortunately, there is no general consensus
among these industries on the multiple policy issues that are critical to the
application of an effective management and disposal program. This paper discusses
the various policy issues that affect these industries and the problems that will
likely occur during the course of their activities. These policy issues include
public and political concern, opposition, and reaction; multiple and sometimes
conflicting government agency jurisdiction, regulation, and policy; issues
relating to the transition to a new comprehensive system; conflicts between the
interests of the various industry groups; and operational, radiation safety, and
regulatory implementation issues. For these reasons, the acceptable options may
be limited. Case studies of various waste streams are included to show the
specific impact and problems that these issues can create.
PMID- 17033466
TI - Improving radioactive waste management: an overview of the Environmental
Protection Agency's low-activity waste effort.
AB - Radioactive waste disposal in the United States is marked by a fragmented
regulatory system, with requirements that often focus on the origin or statutory
definition of the waste, rather than the hazard of the material in question. It
may be possible to enhance public protection by moving toward a system that
provides disposal options appropriate for the hazard presented by the waste in
question. This paper summarizes aspects of an approach focusing on the potential
use, with appropriate conditions, of Resource Conservation and Recovery Act
Subtitle-C hazardous waste landfills for disposal of "low-activity" wastes and
public comments on the suggested approach.
PMID- 17033467
TI - Current status of U.S. Nuclear Regulatory Commission regulatory efforts
controlling the disposition of solid materials.
AB - Current efforts of the U.S. Nuclear Regulatory Commission (U.S. NRC) to develop
rules for the disposition of low-activity solid materials and the outcome of U.S.
NRC rulemaking activities in this area since the late 1990's are described.
International efforts on the disposition of low-activity solid materials and
future plans of the U.S. NRC on this subject are also described.
PMID- 17033468
TI - U.S. Department of Energy policies, directives, and guidance for radiological
control and release of property.
AB - U.S. Department of Energy (U.S. DOE) regulates its operations with a system of
rules, directives, and guidance under the Atomic Energy Act. U.S. DOE's policy is
to conduct its radiological operations in a manner that ensures the health and
safety of its employees, contractors, and the public. U.S. DOE uses an annual
dose limit of 100 mrem (1 mSv) with an "as low as reasonably achievable" (ALARA)
process to achieve radiological protection. The primary directive for radiation
protection of the public and the environment is DOE Order 5400.5. It contains
requirements for the protection of the public and the environment from routine
operations, including controlling and releasing property. Since the publication
of Order 5400.5 in 1990, U.S. DOE has issued guidance for meeting requirements
under it; Guide G 441.1-xx consolidates this guidance. DOE applies a dose
constraint of 25 mrem y (0.25 mSy y(-1)), plus ALARA, for the release of real
property, and 1 mrem y(-1), plus ALARA, for release of personal property. Models
and guidance to develop the needed documentation for release of property are
easily available and user-friendly. While achieving protection of human health
and the environment, U.S. DOE's dose-based release process has resulted in
significant cost savings. U.S. DOE has recently adopted a management systems
approach for general environmental and public protection programs. The
integration of the radiation protection program into this new approach is a high
priority.
PMID- 17033469
TI - Role of state regulatory agencies in the disposition of low-activity radioactive
materials.
AB - Since the opening of the first disposal site for commercially generated low-level
radioactive waste at Beatty, Nevada, in September 1962, the states have been
explicitly involved in the process. The states have been involved as landowners,
regulators, environmental monitors, and sometimes promoters of the sites and/or
the businesses operating the sites.
PMID- 17033470
TI - Rapporteur's summary of presentations at the 2005 NCRP Annual Meeting.
PMID- 17033476
TI - Critical care issues in liver transplantation.
PMID- 17033477
TI - Coagulation and liver transplantation.
PMID- 17033478
TI - Perioperative concerns in acute liver failure.
PMID- 17033479
TI - 6/2/06 Perioperative assessment of the cardiovascular system in ESLD and
transplantation.
PMID- 17033480
TI - Perioperative management of the recipient of the extended criteria cadaveric
donor liver (ECDL): a metabolic approach.
PMID- 17033481
TI - An international look at liver transplantation and anesthesia care.
PMID- 17033482
TI - Status and perspectives of liver transplantation in Argentina.
PMID- 17033483
TI - Perioperative care of liver transplant patients in Brazil.
PMID- 17033484
TI - An experience from China of perioperative care in 1510 liver transplant
recipients.
PMID- 17033485
TI - Perioperative management in adult and pediatric living related liver
transplantation: an Egyptian experience.
PMID- 17033486
TI - Liver transplantation in India.
PMID- 17033487
TI - Liver transplantation in Poland: past, present, and future.
PMID- 17033488
TI - Living donor liver transplantation: perioperative experience from Saudi Arabia.
PMID- 17033493
TI - Methemoglobinemia: a novel way to noninvasively measure it by pulse oximetry.
PMID- 17033494
TI - Lung cancer mortality in the German chromate industry, 1958 to 1998.
PMID- 17033496
TI - The beryllium occupational exposure limit: historical origin and current
inadequacy.
PMID- 17033498
TI - Arsenic exposure and diabetes mellitus risk.
PMID- 17033500
TI - Depression and pesticide exposures in female spouses of licensed pesticide
applicators in the agricultural health study cohort.
AB - OBJECTIVE: This nested case-control study evaluated the association between
depression and pesticide exposure among women. METHODS: The study population
included 29,074 female spouses of private pesticide applicators enrolled in the
Agricultural Health Study between 1993 and 1997. Cases were women who had
physician-diagnosed depression requiring medication. Lifetime pesticide use was
categorized as never mixed/applied pesticides, low exposure (up to 225 days),
high exposure (>225 days), and a history of diagnosed pesticide poisoning.
RESULTS: After adjustment for state, age, race, off-farm work, alcohol, cigarette
smoking, physician visits, and solvent exposure, depression was significantly
associated with a history of pesticide poisoning (odds ratio [OR] = 3.26; 95%
confidence interval [CI] = 1.72-6.19) but not low (OR = 1.09; CI = 0.91-1.31) or
high (OR = 1.09; 95% CI = 0.91-1.31) cumulative pesticide exposure. CONCLUSION:
Pesticide poisoning may contribute to risk of depression.
PMID- 17033501
TI - A projection of the impact of lipid-lowering therapy on high-risk employee
disability and medical costs.
AB - OBJECTIVE: The objective of this study was to examine the impact of introducing
rosuvastatin calcium on direct and indirect costs among patients at high risk for
coronary heart disease. METHODS: An economic simulation model was developed to
project the number of cardiovascular events and associated direct and indirect
costs under varying treatment scenarios. RESULTS: In an average-sized commercial
health plan with 210,000 covered lives and 9,336 high-risk patients, an uptake of
rosuvastatin by 11% of high-risk patients would result in eight fewer
cardiovascular events, a net savings of 0.85 million dollars in direct medical
costs and a net savings of 36,404 dollars in productivity loss over a period of 5
years. The overall reduction in total costs is equivalent to 1735 dollars per
rosuvastatin-treated patient. CONCLUSIONS: At current statin prices, the use of
rosuvastatin could lead to fewer cardiovascular events and lower direct and
indirect costs.
PMID- 17033502
TI - Contribution of burnout to the association between job strain and depression: the
health 2000 study.
AB - OBJECTIVE: The objective of this study was to investigate the contribution of
burnout to the association between job strain and depression. METHODS: A
representative sample of 3270 Finnish employees aged 30 to 64 years responded to
the Maslach Burnout Inventory-General Survey and the Beck Depression Inventory
and participated in the Composite International Diagnostic Interview. RESULTS:
High strain compared with low strain was associated with 7.4 (95% confidence
interval [CI] = 5.6-9.7) times higher odds of burnout, 3.8 (95% CI = 2.8-5.1)
times higher odds of depressive symptoms, and 1.7 (95% CI = 1.1-2.6) times higher
odds of depressive disorders. The risk for depressive symptoms and for depressive
disorders of high strain was reduced by 69% or more after adjusting for burnout.
CONCLUSION: Burnout is strongly related to job strain and may in part mediate the
association between job strain and depression.
PMID- 17033503
TI - Employment as a welder and Parkinson disease among heavy equipment manufacturing
workers.
AB - OBJECTIVE: We investigated whether employment as a welder with potential exposure
to manganese and other substances is associated with Parkinson disease (PD),
parkinsonism or related neurological disorders, or accelerates the age of onset
of PD. METHODS: We selected cases and controls from 12,595 persons ever employed
at three Caterpillar Inc. (CAT) plants between 1976 and 2004 with potential to
make a medical insurance claim between 1998 and 2004. Cases had filed a claim for
1) PD, 2) "secondary parkinsonism", 3) "other degenerative diseases of the basal
ganglia" or 4) "essential and other specific forms of tremor". Cases were grouped
by claims: Group 1-claims 1 and 2 and Group 2-claims 1 to 4, and as study period
incident (SPI) or prevalent. Each case was matched to two series of 10 controls
each on date of case's first claim, year of birth, race and sex. Series I was
also matched on plant. RESULTS: Odds ratios (OR) and 95% confidence intervals
(CI) for the variable, "ever welder in any CAT plant" were: Group 1-SPI Cases:
Series I (OR = .76, CI = .26-2.19), Series II (OR = .81, CI = .29-2.25); Group 1-
Prevalent Cases: Series I (OR = .82, CI = .36-1.86), Series II (OR = .97, CI =
.42-2.23); Group 2- SPI Cases: Series I (OR = 1.03, CI = .57-1.87), Series II (OR
= 1.21, CI = .67-2.20) Group 2-Prevalent Cases: Series I (OR = 1.02, CI = .62
1.71), Series II (OR = .86, CI = .51-1.43). Our finding of no statistically
significant associations for welding employment was maintained following
adjustment for potential confounding and evaluation of possible effect
modification. Employment as a welder did not accelerate the age of onset of PD.
CONCLUSIONS: Our study supported the conclusion that employment as a welder is
not associated with Parkinson disease, parkinsonism or a related neurological
disorder.
PMID- 17033504
TI - Firefighter heart presumption retirements in Massachusetts 1997-2004.
AB - OBJECTIVE: "Heart Presumption" legislation is common throughout North America. We
sought to study Massachusetts firefighters retiring with heart disability awards.
METHODS: The authors conducted a retrospective review of Massachusetts
firefighters: 362 receiving Heart Presumption pensions (1997-2004) and a
comparison group of 310 professionally active firefighters. RESULTS: Of
retirements, 77% were due to coronary heart disease and 23% for other
cardiovascular conditions. Only 42% of the retirements were related to discrete
on-duty events. Fire suppression (odds ratio = 51, 95% confidence interval = 12
223) and alarm response (odds ratio = 6.4, 95% confidence interval = 2.5-17) were
associated with markedly higher risks of duty-related heart retirement events
than nonemergency activities. Cardiovascular risk factor prevalence was high
among all retiree subgroups and significantly greater than among control
firefighters in almost all cases. CONCLUSIONS: Our study supports calls for
improved cardiovascular prevention and risk reduction strategies among
firefighters.
PMID- 17033505
TI - Use of medical insurance claims data for occupational health research.
AB - OBJECTIVE: The objective of this study was to demonstrate that health claims
data, widely available due to the unique nature of the U.S. healthcare system,
can be linked to other relevant databases such as personnel files and exposure
data maintained by large employers. These data offer great potential for
occupational health research. METHODS: In this article, we describe the process
for linking claims data to industrial hygiene exposure data and personnel files
of a single large employer to conduct epidemiologic research. RESULTS: Our
results demonstrate the ability to replicate previously published findings using
commonly maintained data sets and illustrate methodological issues that may arise
as newer hypotheses are tested in this way. CONCLUSIONS: Health claims files
offer potential for epidemiologic research in the United States, although the
full extent and guidelines for successful application await further clarification
through empiric research.
PMID- 17033506
TI - Risk factors for asthma among cosmetology professionals in Colorado.
AB - PROBLEM: After receiving several reports of occupational asthma among cosmetology
professionals, we studied the prevalence, work-attributable risk, and tasks
associated with asthma in this industry. METHODS: We selected a stratified random
sample of cosmeticians, manicurists, barbers, and cosmetologists holding licenses
in Colorado for a mail survey instrument. RESULTS: The prevalence of physician
diagnosed asthma among the 1883 respondents (68% response rate) was 9.3%; of
these, 67 (38%) developed asthma after entering the cosmetology profession.
Multivariate analyses showed that hairstyling, application of artificial nails,
and shaving and honing were significantly associated with asthma arising in the
course of employment (P < 0.005) with relative risks of 2.6-2.9. CONCLUSIONS: The
increased risk of asthma with onset during employment among cosmetologists is
probably attributable to their exposure to sensitizers and irritants in tasks
demonstrated to be associated with asthma.
PMID- 17033507
TI - Mortality among Rocketdyne workers who tested rocket engines, 1948-1999.
AB - OBJECTIVE: The objective of this study was to evaluate potential health risks
associated with testing rocket engines. METHODS: A retrospective cohort mortality
study was conducted of 8372 Rocketdyne workers employed 1948 to 1999 at the Santa
Susana Field Laboratory (SSFL). Standardized mortality ratios (SMRs) and 95%
confidence intervals (CIs) were calculated for all workers, including those
employed at specific test areas where particular fuels, solvents, and chemicals
were used. Dose-response trends were evaluated using Cox proportional hazards
models. RESULTS: SMRs for all cancers were close to population expectations among
SSFL workers overall (SMR = 0.89; CI = 0.82-0.96) and test stand mechanics in
particular (n = 1651; SMR = 1.00; CI = 0.86-1.16), including those likely exposed
to hydrazines (n = 315; SMR = 1.09; CI = 0.75-1.52) or trichloroethylene (TCE) (n
= 1111; SMR = 1.00; CI = 0.83-1.19). Nonsignificant associations were seen
between kidney cancer and TCE, lung cancer and hydrazines, and stomach cancer and
years worked as a test stand mechanic. No trends over exposure categories were
statistically significant. CONCLUSION: Work at the SSFL rocket engine test
facility or as a test stand mechanic was not associated with a significant
increase in cancer mortality overall or for any specific cancer.
PMID- 17033508
TI - Impairment in workers with isocyanate-induced occupational asthma and removed
from exposure in the province of Quebec between 1985 and 2002.
AB - OBJECTIVE: The objective of this project was to assess both the outcome for
patients diagnosed with proven isocyanate-induced occupational asthma (IIOA) by
specific inhalation challenge (SIC) and the functional impairment, 2 years after
cessation of exposure to isocyanates, using the compensation insurance scale
proposed in the province of Quebec. METHODS: We used a retrospective cohort of
233 patients diagnosed in the province of Quebec between 1985 and 2002 and
randomly chose 105 of those patients. We kept 89 subjects with complete data at
T0 (the time of diagnosis) and 79 were reevaluated at T2, approximately 2 years
after their removal from exposure, for final impairment-disability assessment. At
each evaluation (T0 and T2), a clinical examination and lung function tests,
including spirometry and methacholine challenge, were performed. RESULTS: At T2,
79 of 89 patients were reassessed (89%). The remaining patients were lost to
follow up (8) or too unstable to be reassessed for final impairment-disability
settlement (2). No statistical difference was observed for spirometry data and
antiasthmatic medication use between T0 and T2 (P = 0.11). At T2, 73% of patients
were still using short-acting beta2 agonists and 39% inhaled glucocorticoids. A
forced expiratory volume in 1 second variation of +/-10% from T0 to T2 occurred
in 31 subjects (40%). Forced expiratory volume in 1 second worsened in 14 (18%),
remained significantly unchanged in 51 (64%), and improved in 14 (18%).
Nonspecific bronchial hyperresponsiveness (BHR) improved in significantly in 19
(24%); the others remained unchanged. Both were not associated with smoking
status (P > 0.05). Nonspecific BHR was normalized in nine of 79 (11%) patients.
Clinical remission occurred in only four (5%) subjects. The mean impairment
disability score was 21% +/- 13% at 2 years according to the scale used by the
Workers' Compensation Board. CONCLUSIONS: These results show the generally poor
medical outcome of IIOA and suggest the importance of early detection and
withdrawal of the workers from exposure to isocyanates. They also emphasize the
need for medical surveillance program and adequate treatment of patients with
IIOA.
PMID- 17033509
TI - Effect of smoking status on productivity loss.
AB - OBJECTIVE: The objective of this study was to describe health-related
productivity losses in nonsmokers, former smokers, and current smokers using a
large, cross-sectional database of U.S. employees. METHODS: Volunteers completed
the Wellness Inventory, an instrument measuring productivity losses related to 11
health conditions affecting employee health. Results are aggregated, dollarized,
and reported by smoking group. RESULTS: Current smokers missed more days of work
and experienced more unproductive time at work compared with former smokers and
nonsmokers. The average annual cost for lost productivity for nonsmokers was 2623
dollars/year compared with 3246 dollars/year for former smokers and 4430
dollars/year for current smokers. More than half the costs were due to
unproductive time at work. CONCLUSION: Current smokers incurred the highest
productivity losses, which translated into higher costs to employers for current
smokers. Costs were lower for former smokers and nonsmokers.
PMID- 17033512
TI - Hereditary colonic varices--image of the month.
PMID- 17033513
TI - The match for US pediatric gastroenterology and nutrition fellowships.
PMID- 17033514
TI - Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data
and implications for future research.
AB - Although population prevalence is very difficult to establish, nonalcoholic fatty
liver disease (NAFLD) is probably the most common cause of liver disease in the
preadolescent and adolescent age groups. There seems to be an increase in the
prevalence of NAFLD, likely related to the dramatic rise in the incidence of
obesity during the past 3 decades. Despite an increase in public awareness,
overweight/obesity and related conditions, such as NAFLD, remain underdiagnosed
by health care providers. Accurate diagnosis and staging of nonalcoholic
steatohepatitis (NASH) requires liver biopsy. The development of noninvasive
surrogate markers and the advancements in imaging technology will aid in the
screening of large populations at risk for NAFLD. Two distinct histological
patterns of NASH have been identified in the pediatric population, and discrete
clinical and demographic features are observed in children with these 2 patterns.
The propensity for NASH to develop in obese, insulin-resistant pubertal boys of
Hispanic ethnicity or a non-Hispanic white race may provide clues to the
pathogenesis of NAFLD in children. The natural history of pediatric NASH has yet
to be defined, but most biopsies in this age group demonstrate some degree of
fibrosis. In addition, cirrhosis can be observed in children as young as 10
years. While the optimal treatment of pediatric NAFLD has yet to be determined,
lifestyle modification through diet and exercise should be attempted in children
diagnosed with NAFLD. A large, multicenter trial of vitamin E and metformin is
underway as part of the NASH clinical research network.
PMID- 17033515
TI - Rapid growth in infancy: balancing the interests of the child.
AB - Low birth weight is associated with a number of immediate adverse consequences,
and it has been assumed that "catch-up" growth is a "good thing" because "better"
nutritional status is associated with greater childhood health and survival. The
same thinking applies to infants who suffer malnutrition and growth faltering
during weaning. Recent studies suggest that the rapid postnatal growth of babies
is associated with an enhanced risk for obesity, diabetes, hypertension,
cardiovascular disease and osteopenia in later life. If this is true, it has
implications for our recommendations for infant feeding. Insights from
evolutionary biology, life cycle theory, animal husbandry, epidemiology and
comparative zoology suggest that the energetic feeding of underweight infants
should be considered in the context of the whole life cycle and balance the
interests of the child with its likely fortunes in adulthood. Before we revise
our current recommendations, we must consider the meaning of catch-up growth,
what it involves in terms of tissues gained (fat, muscle and bone) and to what
degree association represents causation. In the meantime, it will be prudent to
balance the short- and long-term interests of the child by endeavoring to (1)
optimize maternal nutrition and health, to avoid low birth weight, (2) breast
feed ideally, (3) consider birth weight, gestation and future "nutritional
environment" when making decisions about infant feeding, (4) use appropriate
growth charts, (5) avoid excessive postnatal weight gain, (6) think about the
whole life span and (7) extrapolate from animal studies cautiously.
PMID- 17033516
TI - Interventions to improve cardiovascular risk factors in obese children.
PMID- 17033517
TI - Appropriate management of severe malnutrition greatly contributes to the
reduction of child mortality rate.
PMID- 17033518
TI - Cytokine expression in rat colon during postnatal development: regulation by
glucocorticoids.
AB - OBJECTIVES: Cytokine expression and regulation by glucocorticoids and retinoic
acid were investigated in the colon during postnatal development. MATERIALS AND
METHODS: Gene expression of the transforming growth factors (TGFs) TGF-beta1, TGF
beta2 and TGF-alpha and the proinflammatory cytokines tumor necrosis factor-alpha
(TNF-alpha) and interleukin-1beta (IL-1beta) was evaluated by reverse
transcription-polymerase chain reaction (RT-PCR) in rat colon mucosa during
weaning and in adult rats. Protein expression and distribution of TGF-betas was
analysed in the colon from 14- and 60-day-old animals. The effect of
hydrocortisone administration on mucosal cytokine transcripts (RT-PCR) and of
dexamethasone on the expression of cytokines by the epithelial cell line IEC-18
and 2 subepithelial myofibroblasts (MIC 307-1 and 316) was examined. RESULTS: TGF
beta1 and TGF-beta2 messenger RNAs and proteins decreased in the entire colon
from weaning to adult stages, whereas the amount of TGF-alpha messenger RNA
increased in the proximal colon and decreased in the distal part of the colon in
adult rats in comparison with weanlings. However, proinflammatory cytokines
showed no postnatal changes in the proximal colon but decreased in the distal
part in comparison with weaning rats. Hydrocortisone treatment did not affect
growth factor expression but decreased proinflammatory cytokines. Likewise,
dexamethasone decreased TNF-alpha and IL-1beta gene expression but did not affect
TGF-betas in either epithelial or myofibroblast cells. CONCLUSIONS: During
postnatal maturation, the expression of growth factors and proinflammatory
cytokines decreased in the distal colon, whereas in the proximal colon, a
differential maturation occurs with no changes in proinflammatory cytokines, an
increase in TGF-alpha and a decrease in TGF-beta. Glucocorticoids may control the
developmental profile of proinflammatory cytokines.
PMID- 17033519
TI - Stimulation of immunity without alteration of oral tolerance in mice fed with
heat-treated fermented infant formula.
AB - OBJECTIVES: Little information is available on the properties of fermented milk
formula intended to healthy infants. This study analyzes the effect of long-term
ingestion of a heat-treated, fermented milk formula on the development of oral
tolerance or systemic immune response to soluble antigens in mice. MATERIALS AND
METHODS: The C3H/HeN mice, fed with a heat-treated fermented (Bifidobacterium
breve C50 and Streptococcus thermophilus 065) infant formula (htFF) or a matched
control diet (control), were immunized with ovalbumin (OVA) with or without
gavage of 20 mg OVA to induce tolerance or immunity, respectively. Systemic and
local anti-OVA immune responses and intestinal barrier function were measured
after 5 to 6 weeks. RESULTS: Oral tolerance to OVA developed similarly in htFF-
and control-fed mice, attested to by the downregulation of OVA-specific
immunoglobulin (Ig) G and IgE after oral OVA administration. In contrast,
immunization with OVA led to significantly higher titers in htFF-fed mice than in
control-fed mice (log2 IgG titers, 16.45 +/- 1.24 and 15.46 +/- 0.79,
respectively; P = 0.012). Jejunal interferon gamma, interleukin 12p40 and
interleukin 10 expressions were significantly higher in tolerized mice fed with
htFF compared with those fed with the control diet. Mucosal to serosal intact
horseradish peroxidase fluxes were lower in htFF-fed mice than in control-fed
mice (39 +/- 8 and 118 +/- 38 ng/h x cm2, respectively; P < 0.0001), indicating
that the htFF diet reinforces intestinal barrier capacity to macromolecules.
CONCLUSIONS: In mice, htFF strengthens intestinal barrier and enhances systemic
immune responses to antigens without interfering with the development of oral
tolerance, suggesting a potential beneficial effect in host defence and
vaccination.
PMID- 17033520
TI - In vivo and in vitro effects of tea extracts on enterotoxigenic Escherichia coli
induced intestinal fluid loss in animal models.
AB - OBJECTIVES: Enterotoxigenic Escherichia coli (ETEC) infection is a major cause of
dehydrating diarrhoea in infants and early-weaned piglets living under
subhygienic conditions. We studied the effect of different tea types and
subfractions on the intestinal fluid and electrolyte losses involved in ETEC
diarrhoea. MATERIALS AND METHODS: Jejunal segments of anaesthetised piglets were
infected with ETEC or ETEC heat-labile toxin (LT) and subsequently perfused for 8
hours with control or tea solutions containing green or black tea extract (BTE)
or 3 different BTE subfractions containing small-size, large-size or no
phenolics. Changes in intestinal fluid and electrolyte net absorption were
measured. To assess the antisecretory effects of tea, BTE was incubated before or
after administration of the secretagogue forskolin in rat jejunal tissue placed
in Ussing chambers and Cl- secretion measured as changes in short-circuit current
(I(SC)). RESULTS: Enterotoxigenic E. coli infection of piglet jejunal segments
significantly reduced net absorption of fluid, Na+ and Cl- and increased net
secretion of K+ compared with controls. Perfusion of the ETEC-infected segments
with both 3 g/L green tea extract and BTE significantly inhibited these
disturbances in fluid and electrolyte balance. The BTE subfraction rich in
polymeric phenolics but not the other subfractions improved the fluid and
electrolyte balance. Addition of forskolin to rat jejunal tissue induced a
significant increase in I(SC). Pretreating but not posttreating the jejunal
tissue with BTE inhibited the forskolin-induced increase in I(SC). CONCLUSIONS:
Tea may inhibit net fluid and electrolyte losses involved in secretory diarrhoea
from ETEC.
PMID- 17033521
TI - Intestinal cytokine mRNA expression in delayed-type cow's milk allergy.
AB - OBJECTIVES: The aim of the study was to investigate the characteristics of
intestinal immune activation (ie, a chemokine receptor and cytokine expression
profile) in delayed-type cow's milk allergy (CMA) appearing in the form of
gastrointestinal symptoms. PATIENTS AND METHODS: In all biopsy samples taken from
the duodenum and/or the terminal ileum, 30 were studied for the expression of
interferon-gamma, transforming growth factor-beta, chemokine receptor (CCR)-4,
CCR-5, IL-2, IL-6, IL-10, IL-12p35, IL-12p40 and IL-18 specific mRNA by real-time
quantitative reverse transcriptase-polymerase chain reaction in 26 children ages
3 to 15 years: 10 with untreated delayed-type CMA, 6 with celiac disease (CD) and
10 controls. RESULTS: The children with delayed-type CMA showed lower IL-2 and IL
18 mRNA expression in the duodenum (both P = 0.055) and higher CCR-4 and IL-6
mRNA expression in the terminal ileum (P = 0.055, P = 0.016) compared with the
controls. The children with CD exhibited slightly higher expression of interferon
gamma and CCR-4 mRNA (P = 0.054, P = 0.053) and lower expression of IL-18 mRNA (P
= 0.004) in the duodenal samples compared with the controls. The mRNA expression
levels of regulatory cytokines, transforming growth factor-beta and IL-10
remained similar in all 3 groups. CONCLUSIONS: The children with delayed-type
gastrointestinal CMA showed a unique pattern of local intestinal hypersensitivity
with Th2 response-related characteristics, a profile differing clearly from the
children with CD.
PMID- 17033522
TI - A prospective community-based study of gastroenterological symptoms in school-age
children.
AB - INTRODUCTION: Current knowledge on the prevalence of common gastrointestinal (GI)
problems is based on office-based samples or retrospective questionnaires,
leading to possible bias and inaccurate estimates. AIMS: To examine the
prevalence of GI symptoms in school-age children. IMPORTANCE: This is the first
American prospective community study intended to assess the prevalence of common
GI symptoms in children. PATIENTS AND METHODS: All fourth- and fifth-grade
students from a middle-size urban school were invited to participate in a
prospective cohort pilot study by completing confidential weekly surveys. The
survey included a set of 8 age-appropriate, validated questions assessing the
presence and severity of abdominal pain, constipation, diarrhea, nausea,
vomiting, chest pain, headaches and limb pain. RESULTS: A total of 48 children
(32 boys and 16 girls) participated in the study. Data were obtained for 16 weeks
on 690 (90.5%) of 768 possible children per week. Children reported at least 1
symptom in 544 (70%) children per week. Headaches were the most common complaint
(55% [range, 40%-72%] children per week). Sixty percent of children (range, 46%
89%) reported at least 1 GI symptom weekly. The overall prevalence of GI symptoms
was the following: abdominal pain 46% (range, 28%-72%), nausea 28% (range, 17%
59%), constipation 18% (range, 7%-39%), diarrhea 17% (range, 11%-24%) and
vomiting 5% (range, 0%-13%). None of the children missed school because of
persistent GI symptoms during the study. DISCUSSION: The investigation
demonstrates the feasibility of prospective school studies in children. The high
prevalence of GI symptoms not interfering with school attendance in children
underscores the benign nature of such symptoms in most children. CONCLUSION:
Gastrointestinal symptoms are common somatic complaints among school-age
children.
PMID- 17033523
TI - Patient-reported symptoms after pediatric outpatient colonoscopy or flexible
sigmoidoscopy under general anesthesia.
AB - OBJECTIVES: Endoscopic examination of the colon is indicated in children with
diarrhea, hematochezia and suspected inflammatory bowel disease. The aim of this
study was to determine the rate of patient-reported symptoms after colonoscopy
and flexible sigmoidoscopy under general anesthesia in children. PATIENTS AND
METHODS: This prospective study included patients 18 years of age and younger who
underwent colonoscopy or flexible sigmoidoscopy during a 1-year period. At least
30 days after the endoscopy, an interview was conducted regarding symptoms after
colonoscopy or flexible sigmoidoscopy. RESULTS: Eighty-eight children were
eligible, and 68 (77%) were available for follow-up. Ten (15%) reported symptoms
after their endoscopy. The most common symptoms reported were diarrhea, excessive
gas and sore throat. The frequency of reported symptoms was similar between
colonoscopy and flexible sigmoidoscopy. The frequency of symptoms was not
affected by intubation of terminal ileum, polypectomy or the number of prior
colonoscopies or flexible sigmoidoscopies. CONCLUSIONS: Outpatient colonoscopy
and flexible sigmoidoscopy under general anesthesia are well tolerated by
children. A minority of children reports mild symptoms that spontaneously
resolve.
PMID- 17033524
TI - Liver transplantation and chemotherapy in children with unresectable primary
hepatic malignancies: development of a management algorithm.
AB - OBJECTIVES: Total surgical excision and adjunctive chemotherapy are cornerstones
of treatment of primary hepatic malignancies in children. Recent studies suggest
that transplantation is a viable option for unresectable tumors, but there are
questions concerning decision making regarding resectability and timing of
transplantation in relation to chemotherapy. We developed a management algorithm
based on our experience, with reference to recently published multicenter
transplantation outcomes. RESULTS: Nine patients underwent transplantation
(median age, 38 months; 7 hepatoblastoma, 2 undifferentiated mesenchymal
sarcoma). All were assessed unresectable at presentation. After chemotherapy, 7
remained unresectable and had primary transplantation, 1 developed chemotherapy
related liver failure, necessitating emergent transplantation, and 1 was deemed
resectable, requiring rescue transplantation after local recurrence. Using a
timely living/cadaver donor graft acquisition strategy relative to chemotherapy,
median waiting time from listing was 8 days. After transplantation, 3 of 9 had
chemotherapy, with side effects dictating discontinuation in 2; 6 of 9 had no
chemotherapy, with 2 developing distant metastases, 1 of whom died 12 months
posttransplantation. Median follow-up was 3.08 years. Overall survival was 89%.
CONCLUSIONS: Primary transplantation can be highly successful in children with
hepatic tumors. These outcomes compare favorably with multicenter studies, where
waiting-list deaths are reported and survival after rescue transplantation is
poor. We encourage timely transplantation in the setting of questionably
resectable tumors or evidence of chemotherapy resistance. The necessity of
posttransplantation chemotherapy is questioned. Consultation with a
transplantation program before chemotherapy should avoid inappropriate attempts
at resection and allow appropriate planning of transplantation in relation to
chemotherapy.
PMID- 17033525
TI - Long-term lamivudine therapy for chronic hepatitis B infection in children
unresponsive to interferon.
AB - OBJECTIVES: Prolonged lamivudine treatment in adults has been shown to improve
hepatitis B e (HBe) seroconversion rates in patients with chronic hepatitis B.
This prospective open study reports the results of prolonged lamivudine treatment
in a group of children with chronic hepatitis B. PATIENTS AND METHODS: Twenty-two
children and adolescents age 13.2 years (range, 9.5-18 years), who have been
treated with lamivudine for 1 year, continued treatment with lamivudine (3
mg/kg/day, up to 100 mg/d) as long as there was evidence of continued biochemical
and virological benefit compared with baseline. We evaluated virological and
biochemical responses, the occurrence of YMDD mutants and adverse effects during
4 years of follow-up. RESULTS: After 4 years on lamivudine, only 4 patients (18%)
underwent HBe seroconversion. In addition, in 3 patients (13%), the treatment was
stopped when lamivudine's lack of efficacy became evident. During the 4-year
study period, we recorded a continuing decline in the participants' number,
mostly because of lack of compliance with treatment (9/22, 41%). Only 5 children
were still receiving lamivudine and showing benefit after 4 years. In 2 children,
treatment termination and YMDD mutant emergence were associated with hepatitis
flare. Besides subclinical elevation of creatine phosphokinase, no other adverse
events were recorded during the study period. CONCLUSIONS: Four years after
starting lamivudine treatment, most children from this study were off lamivudine,
mainly because of lack of compliance and poor HBe seroconversion. These findings
suggest that continuing treatment with lamivudine for undefined periods is hard
to implement and does not improve HBe seroconversion.
PMID- 17033526
TI - Safety, efficacy and pharmacokinetics of peginterferon alpha2a (40 kd) in
children with chronic hepatitis C.
AB - Chronic hepatitis C virus (HCV) infection in children is a problem affecting
thousands of children worldwide. Although standard interferon (INF) has better
efficacy in pediatric patients than in adults, results in children with genotype
1 are poor; response rates to combination treatment with standard INF and
ribavirin are better but the treatment requires thrice-weekly injections. The
improved antiviral efficacy of weekly pegylated interferons relative to standard
interferons in adults with chronic HCV infection suggests that pegylated
interferons may also improve antiviral efficacy in children. We therefore
investigated the pharmacokinetics, efficacy and safety of peginterferon alpha2a
(pegINF-alpha2a) (40 kd) in 14 children ages 2 to 8 years with chronic hepatitis
C (13 genotype 1, 1 non-1 genotype). Drug dose was calculated from each patient's
body surface area (BSA) according to the formula BSA (m2)/(1.73 m2) x 180 microg,
and patients were administered once-weekly subcutaneous injections for 48 weeks.
Viral load and pharmacokinetic parameters were determined from blood drawn
throughout the study and during follow-up. At week 24, the mean trough
concentration was about 20% below values obtained from adults treated with pegINF
alpha2a, and the area under the curve from 0 to 168 hours was about 20% above
adult values, suggesting that drug doses calculated from BSA achieved
therapeutically adequate concentrations. Six of 14 patients (43%), all infected
with genotype 1, achieved a sustained virological response. Adverse events were
those commonly associated with INF-based treatment, and none was deemed serious.
In conclusion, our findings provide a basis for larger studies evaluating the
efficacy and safety of pegINF-alpha2a as monotherapy as well as in combination
with ribavirin in pediatric patients with chronic hepatitis C.
PMID- 17033527
TI - Changes of cardiovascular risk factors in obese children effects of inpatient and
outpatient interventions.
AB - OBJECTIVE: The aim of the study was to compare the benefits of 2 different
therapeutic approaches on cardiovascular risk factors (CVRF) in obese children
and adolescents. METHODS: We analyzed the changes of weight status (as standard
deviation score-body mass index [SDS-BMI]), blood pressure, lipids, and insulin
levels in obese children (age range, 10-14 years) during a 1-year outpatient
intervention based on lifestyle changes (group A, n = 124) and during a 6-week
inpatient intervention program with dietary restriction and exercise therapy
(group B, n = 119). In addition, we studied these parameters in 65 obese children
without intervention for 1 year (control group). RESULTS: Age, degree of
overweight, sex, and CVRF did not differ significantly between the control group
and the intervention groups at baseline. During the observation period, CVRF did
not change in the control group, whereas SDS-BMI slightly increased (+0.1 SDS
BMI). The SDS-BMI decreased significantly (P < 0.001) in group A (SDS-BMI, -0.40)
and comparably in group B (SDS-BMI, -0.43). The decreases of total (P < 0.001)
and low-density lipoprotein-cholesterol levels (P = 0.049) were significantly
greater in group B, whereas triglyceride (P = 0.040) and insulin (P = 0.006)
levels decreased significantly and were more pronounced in group A. High-density
lipoprotein-cholesterol level increased significantly (P < 0.001) only in group
A. Blood pressure decreased significantly (P < 0.01) and comparably in both
intervention groups (A and B). CONCLUSIONS: In contrast to obese children without
intervention, CVRF improved in obese children with intervention. The 6-week
inpatient intervention led to a significant greater decrease of total and low
density lipoprotein-cholesterol levels as compared with the 1-year outpatient
intervention, although the outpatient intervention yielded a significantly
greater improvement in insulin, triglycerides, and high-density lipoprotein
cholesterol levels.
PMID- 17033528
TI - Effect of a low-cost food on the recovery and death rate of malnourished
children.
AB - OBJECTIVES: Nutritional rehabilitation in Africa relies mainly on imported skim
milk enriched with a sugar and salt mixture. We evaluated whether milk plus
porridge made from local ingredients improves the outcome of childhood
nutritional rehabilitation versus milk alone. PATIENTS AND METHODS: This study
was conducted in a nutritional unit in Lacor (Northern Uganda). The porridge,
made from cheap locally available ingredients (maize flour, dried fish or meat,
peanut butter and oil) supplemented with proteins and fats, provides 1.1 energy
units, 4.4 kJ/g. We randomly sampled the files of 100 cases discharged in
October, November and December 2001 (preintervention), in 2002 (soon after
intervention onset) and in 2003 (more than 1 year after intervention onset). We
recorded the average hospital days and average oedema-free weight gain at
discharge in the 3 groups. RESULTS: Average oedema-free weight gain increased
from 21 g/d (95% confidence interval [CI], 12-29) in 2001 to 35 g/d (95% CI, 25
45) in 2002 and reached 59 g/d (95% CI, 51-65) in 2003. Mortality decreased from
22% to 7.8%, and nutritional failures (insufficient weight gain) decreased by
greater than 50%. CONCLUSIONS: The low-cost porridge supplement (2640 euros/yr
per 100 children) was effective in treating malnutrition. Widespread use of the
porridge, which resulted in better outcomes than milk alone, could produce a
savings in the medium- to long-term, thereby releasing resources for other uses.
A high-energy porridge that is made from locally available ingredients and does
not require imported foods seems to be appropriate for supplementary feeding
after mother's milk in this setting.
PMID- 17033529
TI - Effects of age and time on energy and macronutrient intake in German infants and
young children: results of the DONALD study.
AB - OBJECTIVES: To describe effects of age and time on the intake of energy and
macronutrients in infants and young children. PATIENTS AND METHODS: The energy
and macronutrient intake of 720 DONALD study participants between 1989 and 2003
was evaluated by analysing 3027 three-day weighed dietary records (including test
weighing of breast milk consumption) at 3, 6, 9, 12, 18, 24 and 36 months. Mixed
models and logistic regression analyses were used to investigate the effects of
age and time on intake. RESULTS: Age affected macronutrient patterns (percentage
of energy intake, E%) more often in infants than in young children. The
percentage of full and partial breast-fed infants increased between 1989 and
2003. Almost no time trends were found for energy intake. Macronutrient patterns
changed with time; for example, protein intake decreased throughout infancy
(between -0.05 and -0.17 E%/y). An increase in fat intake (0.23 and 0.40 E%/y)
was compensated by a decrease in carbohydrates (-0.18 and -0.29 E%/y) in young
infants (3 and 6 months). Opposite trends in macronutrient patterns were observed
in infants and young children. CONCLUSIONS: Increasing breast milk consumption
over time was the most obvious factor influencing long-term trends in
macronutrient patterns. In all of the age groups examined here, macronutrient
patterns have come closer to the references over time.
PMID- 17033530
TI - Growth and change in blood haemoglobin concentration among underweight Malawian
infants receiving fortified spreads for 12 weeks: a preliminary trial.
AB - OBJECTIVE: Fortified spreads (FSs) have proven effective in the rehabilitation of
severely malnourished children. We examined acceptability, growth and change in
blood haemoglobin (Hb) concentration among moderately underweight ambulatory
infants given FS. METHODS: This was a randomised, controlled, parallel-group,
investigator-blind clinical trial in rural Malawi. Six- to 17-month-old
underweight infants (weight for age < -2), whose weight was greater than 5.5 kg
and weight-for-height z score greater than -3 received for 12 weeks at home 1 of
8 food supplementation schemes: nothing, 5, 25, 50, or 75 g/day milk-based FS or
25, 50, or 75 g/day soy-based FS. Outcome measures included change in weight,
length and blood Hb concentration. RESULTS: A total of 126 infants started and
125 completed the intervention. All infants accepted the spread well, and no
intolerance was recorded. Average weight and length gains were higher among
infants receiving daily 25 to 75 g FS than among those receiving only 0 to 5 g
FS. Mean Hb concentration remained unchanged among unsupplemented controls but
increased by 10 to 17 g/L among infants receiving any FS. All average gains were
largest among infants receiving 50 g of FS daily: mean difference (95% confidence
interval) in the 12-week gain between infants in 50 g milk-based FS group and the
unsupplemented group was 290 g (range, -130 to 700 g), 0.9 cm (range, -0.3 to 2.2
cm), and 17 g/L (range, 0 to 34 g/L) for weight, length and blood Hb
concentration, respectively. In soy- vs milk-based FS groups, average outcomes
were comparable. CONCLUSIONS: Supplementation with 25 to 75 g/day of highly
fortified spread is feasible and may promote growth and alleviate anaemia among
moderately malnourished infants. Further trials should test this hypothesis.
PMID- 17033531
TI - Vertebral fractures and increased sensitivity to corticosteroids in a child with
ulcerative colitis: successful use of pamidronate.
PMID- 17033532
TI - Acute hepatitis and liver failure associated with influenza A infection in
children.
PMID- 17033533
TI - Gastric pneumatosis intestinalis: an indicator of intestinal perforation in
preterm infants with necrotizing enterocolitis?
PMID- 17033534
TI - A child with Kabuki syndrome and primary sclerosing cholangitis successfully
treated with ursodiol and cholestryamine.
PMID- 17033535
TI - Therapy with gastric acidity inhibitors increases the risk of acute
gastroenteritis and community-acquired pneumonia in children.
PMID- 17033536
TI - Antiemetics for acute gastroenteritis: a never ending story.
PMID- 17033537
TI - The adipokine visfatin is markedly elevated in obese children.
AB - OBJECTIVE: The insulin-mimetic adipocytokine visfatin has been linked to
adiposity and the metabolic syndrome. DESIGN: Cross-sectional study. SUBJECTS:
Eighty-three nondiabetic obese children and 40 healthy controls. MEASUREMENTS: We
analyzed plasma visfatin concentrations to assess whether this adipokine is
associated with adiposity. RESULTS: Plasma visfatin concentrations were nearly 2
fold higher in obese children (mean, 1.1 ng/mL; 95% CI, 0.2-6.6) than in controls
(0.6 ng/mL, 95% CI, 0.6 to 0.6; P < 0.001). No relationship was detectable
between visfatin and other subject characteristics, hsCRP or the lipid profile.
CONCLUSIONS: Visfatin may be involved in the development of metabolic
derangements in obese children.
PMID- 17033538
TI - Clinical efficacy of probiotics: review of the evidence with focus on children.
AB - Probiotics are marketed in several countries and widely used by pediatric health
care providers. Although probiotics can be helpful for specific disorders, they
have been broadly prescribed for disorders without clear evidence to support
their use. Furthermore, in certain specific conditions, probiotics cause clinical
deterioration. This report is a review and evaluation of the evidence or lack
thereof to support a beneficial effect of probiotic agents in a variety of
pediatric conditions and to review the safety and potential adverse events that
may be encountered when using probiotics. It is also important to emphasize that
probiotics are highly heterogeneous with differences in composition, biological
activity, and dose among the different probiotic preparations.
PMID- 17033539
TI - The future of emergency care for America: in crisis, at peril and in need of
resuscitation!
PMID- 17033540
TI - Do early ionized calcium levels really matter in trauma patients?
AB - BACKGROUND: Age, injury severity, and base deficit are commonly used prognostic
indicators in trauma. This study investigates the relationship between ionized
calcium (iCa) levels drawn on arrival to the emergency department, with injury
severity, acidosis, hypotension, and mortality. METHODS: Adult trauma team
activations requiring the highest level of response were identified
retrospectively from January 2000 to December 2002. Patients were stratified into
two groups: iCa < or = 1 and iCa > 1 mmol/L. The relationship between iCa and
injury severity (Trauma Injury Severity Score, Injury Severity Score [ISS],
Revised Trauma Scale, Glasgow Coma Scale), age, sampling time, shock (systolic
blood pressure [SBP] < 90 at the scene, transport, and admission; base deficit),
resource utilization (hospital and intensive care unit length of stay, ventilator
days) and mortality was examined. Statistical analysis included chi2 tests,
Wilcoxon rank sum tests, p < 0.05 versus iCa > 1, median (25th-75th percentile),
and odds ratio (OR). RESULTS: In all, 396 out of 2,367 patients were identified.
Mortality was significantly increased in the iCa < or = 1 group (26.4% versus
16.7%, p < 0.05; OR 1.92). Time to death in iCa < or = 1 was significantly
shorter, 0.50 (0-1) versus 1.0 (0-6) days. Mortality was predicted using iCa < or
= 1 alone (p < 0.02, OR 3.28), iCa < or = 1 + base deficit (p < 0.02, OR 2.00),
and base deficit alone (p = 0.06, OR 1.5). Low iCa was associated with SBP < 90
at the scene and transport (p < 0.01). The incidence of base deficit was higher
in the iCa < or = 1 group (p < 0.05). CONCLUSIONS: Low iCa is associated with
prehospital hypotension regardless of age, ISS, or sampling time and is a better
predictor of mortality than base deficit. Since acidosis reduces calcium binding
to serum protein and actually increases iCa, the association between base deficit
and iCa in this study requires further investigation.
PMID- 17033541
TI - Continuous muscle tissue oxygenation in critically injured patients: a
prospective observational study.
AB - BACKGROUND: Despite normalization of vital signs, critically injured patients may
remain in a state of occult underresuscitation that sets the stage for sepsis,
organ failure, and death. A continuous, sensitive, and accurate measure of
resuscitation after injury remains elusive. METHODS: In this pilot study, we
evaluated the ability of two continuous measures of peripheral tissue oxygenation
in their ability to detect hypoperfusion: the Licox polarographic tissue oxygen
monitor (PmO2) and the InSpectra near-infrared spectrometer (StO2). We
hypothesized that deltoid muscle tissue oxygenation measurements could detect
patients in "occult shock" who are at increased risk for post-injury
complications. The study was designed to (1) define values for PmO2 and StO2 in
patients who by all standard measures appeared to be clinically resuscitated; (2)
evaluate the relationship between PmO2, StO2 and other physiologic variables
including mean arterial pressure (MAP), lactate and base deficit (BD); and (3)
examine the relationship between early low tissue oxygen values and the
subsequent development of infections and organ dysfunction. Licox probes were
inserted into the deltoid muscle of critically injured patients after initial
surgical and radiologic interventions, and transcutaneous StO2 monitors were
applied over the same muscle bed. PmO2, StO2, and standard physiologic data were
collected continuously using a multimodal bioinformatics system. RESULTS: Twenty
eight critically injured patients were enrolled in this study at admission to the
intensive care unit (ICU). For patients who appeared to be well resuscitated
(defined as MAP > or = 70 mm Hg, heart rate [HR] < or = 110 bpm, BD > or = -2,
and partial pressure of arterial oxygen (PaO2) = 80 and 150 mm Hg), the mean PmO2
was 34 +/- 11 mm Hg and StO2 was 63 +/- 27%. There was a strong relationship
between PmO2 and BD (p < 0.001) but no significant relationship between StO2 and
BD. The relationship between PmO2 and StO2 was weak but statistically
significant. Early low values of both PmO2 and StO2 identified patients at risk
for infectious complications or multiple organ failure (MOF). In patients who
were well resuscitated by standard continuous parameters (HR and MAP), low PmO2
during the first 24 hours after admission (PmO2 < or = 25 for at least 2 hours)
was strongly associated with the development of infectious complications (Odds
Ratio = 16.5, 95% CI 1.49 to 183, p = 0.02). CONCLUSIONS: PmO2 is a responsive,
reliable and continuous monitor of changes in base deficit. Initial low values
for either PmO2 or StO2 were associated with post-injury complications. PmO2
monitoring may be useful in identifying patients in the state of occult
underresuscitation who remain at risk for developing infection and MOF.
PMID- 17033542
TI - Predicting quality of life six months after traumatic injury.
AB - BACKGROUND: Many factors are known to impact quality of life (QoL) after injury,
but predictors of diminished QoL and the time course of recovery remain
incompletely understood. This study examines predictors and correlates of QoL
measured by the Short Form-36 (SF-36) one and six months postinjury. METHODS:
Adults with nonneurologic blunt injury were prospectively enrolled. Demographic,
injury, and socioeconomic data were collected. Patients were assessed with
functional and psychologic measures. In all, 196 patients had 1-month data and
123 had 6-month data available. Scores were compared at each time point and also
to population norms using t-tests. Multiple regression techniques were used to
identify associations between the physical and mental component scores (PCS &
MCS) of the SF-36 and patient characteristics. RESULTS: PCS scores improved
significantly (32.8 +/- 0.9 versus 41.3 +/- 1.0, p < 0.05) whereas MCS scores
(47.5 +/- 1.1 versus 47.2 +/- 1.1, p = NS) did not. Both remained significantly
below population norms. Functional Independence Measure (FIM) at one month was
predictive of PCS at 6 months. Posttraumatic stress disorder (PTSD) was
predictive of lower MCS, and depression was associated with poor MCS. Injury
Severity Score was not associated with PCS or MCS. CONCLUSIONS: Overall physical
and mental QoL measured by the SF-36 remains significantly below population norms
6 months after traumatic injury. It is possible to identify patients at risk for
diminished QoL early during recovery by screening for functional status, PTSD,
social support, and depression. Interventions to address these areas should be
further studied with respect to their impact on long-term QoL.
PMID- 17033543
TI - Longitudinal study of suicide after traumatic injury.
AB - BACKGROUND: Suicide risk after discharge among trauma patients could be
influenced by multiple factors. The aim of this study is to establish whether
patients discharged from a trauma center experience an increased suicide rate and
whether this can be explained by defined demographic, injury, or alcohol abuse
risk factors. METHODS: Patients admitted between July 1, 1983, and June 30, 1995,
and discharged alive from a Level I trauma center (n = 27,399) were followed for
1.5 to 14.5 years to determine whether they had died. Death determination was
made by an epidemiologic support service, which had created a repository of death
certificates. Variables used in the analyses included age, gender, race, Injury
Severity Score, discharge disposition, mechanism of injury, and alcohol
toxicology. General and trauma populations were compared using standard mortality
rates. Risk factors for suicide within the trauma population were explored using
Pearson's chi2, Mantel-Haenszel chi2, Cox proportional hazards, and Mantel-Cox
log-rank methodology. RESULTS: Suicide was more common in the trauma than in the
general population (standard mortality rate = 1.71). This difference may be
attributed primarily to alcohol use problems. Suicide risk in the trauma
population increased with age from 25 to 44 years, male gender, Caucasian race,
and positive alcohol toxicology. Disability (as measured by discharge
disposition), but not injury severity, also seemed to have an influence on
suicide rates. CONCLUSION: Interventions that address modifiable risk factors for
suicide (substance abuse, psychiatric disorders, hopelessness, and social
isolation) could benefit trauma patients known to be at higher risk for suicide,
particularly those abusing alcohol.
PMID- 17033544
TI - The effect of computerized tailored brief advice on at-risk drinking in
subcritically injured trauma patients.
AB - BACKGROUND: One-third of injured patients treated in the emergency department
(ED) have an alcohol use disorder (AUD). Few are screened and receive counseling
because ED staff have little time for additional tasks. We hypothesized that
computer technology can screen and provide an intervention that reduces at-risk
drinking (British Medical Association criteria) in injured ED patients. METHODS:
In all, 3,026 subcritically injured patients admitted to an ED were screened for
an AUD using a laptop computer that administered the AUD Identification Test
(AUDIT) and assessed motivation to reduce drinking. Patients with a positive
AUDIT (n = 1,139) were randomized to an intervention (n = 563) or control (n =
576) condition. The computer generated a customized printout based on the
patient's own alcohol use pattern, level of motivation, and personal factors,
which was provided in the form of feedback and advice. RESULTS: Most patients
(85%) used the computer with minimal assistance. At study entry, a similar
proportion in each group met criteria for at-risk drinking (49.6% versus 46.8%, p
= 0.355). At 6 months, 21.7% of intervention and 30.4% of control patients met
criteria for at-risk drinking (p = 0.008). Intervention patients also had a 35.7%
decrease in alcohol intake, compared with a 20.5% decrease in controls (p =
0.006). At 12 months, alcohol intake decreased by 22.8% in the intervention group
versus 10.9% in controls (p = 0.023), but the proportion of at-risk drinkers did
not significantly differ (37.3% versus 42.6%, p = 0.168). CONCLUSIONS: The
computer-generated intervention was associated with a significant decrease in
alcohol use and at-risk drinking. Research is needed to further evaluate and
adapt information technology to provide preventive clinical services in the ED.
PMID- 17033545
TI - Is fecal diversion necessary for nondestructive penetrating extraperitoneal
rectal injuries?
AB - BACKGROUND: Current management of penetrating extraperitoneal rectal injury
includes diversion of the fecal stream. The purpose of this study is to assess
whether nondestructive penetrating extraperitoneal rectal injuries can be managed
successfully without diversion of the fecal stream. METHODS: This study was
performed at an urban Level I trauma center during a 28-month period from
February 2003 through June 2005. All patients who suffered nondestructive
penetrating extraperitoneal rectal injuries were managed with a diagnosis and
treatment protocol that excluded fecal stream diversion. Patients were placed in
one of two management arms based upon clinical suspicion for intraperitoneal
injury. In the first arm, patients with suspicion for rectal injury and a
positive clinical examination for intraperitoneal injuries were delivered to the
operating room for exploratory laparotomy. Proctoscopy was performed before
exploratory laparotomy. Extraperitoneal rectal injuries were left to heal by
secondary intention. Intraperitoneal rectal injuries were repaired primarily.
Patients did not receive fecal diversion or perineal drainage. In the second
management arm, patients with a negative clinical examination for intraperitoneal
injury and wounding agent trajectory suspicious for rectal injury underwent
diagnostic peritoneal lavage (DPL), cystography, and proctoscopy in the emergency
room. Positive DPL or cystography warranted laparotomy as above. Patients with
positive proctoscopy alone were admitted and placed on a clear liquid diet.
Barium enema was performed 5 to 7 days postinjury for all rectal injuries with
diets advanced accordingly.A matched historic control group of rectal injury
patients who underwent fecal diversion was compared with the nondiversion
protocol group. Patients from both groups were matched for penetrating abdominal
trauma index (PATI), age and mechanism of injury. RESULTS: There were 14
consecutive patients diagnosed with penetrating rectal injury placed in the
nondiversion management protocol. Of these, 9 (64%) patients in the nondiversion
group required laparotomy. The average age in the diversion historical control
group was 30.5 years and 29.3 years in the nondiversion group. The average PATI
in the diversion group was 15.3 and 16.1 in the nondiversion protocol group. The
average length of stay for the diversion and nondiversion groups was 9.8 days
(range, 7-15) and 7.2 days (range, 4-10), respectively. There were no
complications associated with rectal injuries in either group. CONCLUSIONS:
Nondestructive penetrating rectal injuries can be managed successfully without
fecal diversion. Randomized prospective study will be necessary to assess this
management method.
PMID- 17033546
TI - Admission physiology criteria after injury on the battlefield predict medical
resource utilization and patient mortality.
AB - BACKGROUND: Medical resources and resource allocation including operating room
and blood utilization are of prime importance in the modern combat environment.
We hypothesized that easily measurable admission physiologic criteria and injury
site as well as injury severity calculated after diagnostic evaluation or
surgical intervention, would be strongly correlated with resource utilization and
in theater mortality outcomes. METHODS: We retrospectively reviewed the Joint
Theater Trauma Registry for all battlefield casualties presenting to surgical
component facilities during Operation Iraqi Freedom from January to July 2004.
Data were collected from the composite population of 1,127 battlefield casualty
patients with respect to demographics, mechanism, presentation physiology (blood
pressure, heart rate, temperature), base deficit, admission hematocrit, Glasgow
Coma Score (GCS), Injury Severity Score (ISS), operating room utilization, blood
transfusion, and mortality. Univariate and multivariate analyses were conducted
to determine the degree to which admission physiology and injury severity
correlated with blood utilization, necessity for operation, and acute mortality.
RESULTS: Univariate analysis demonstrated a significant (p < 0.05) association
between hypothermia (T < 34 degrees C) and the subsequent requirement for
operation and mortality. In addition, the outcome variable total blood product
utilization was significantly correlated with base deficit (r = 0.61), admission
hematocrit (r = 0.51), temperature (r = 0.47), and ISS (r = 0.54). Using multiple
logistic regression techniques, blood pressure, GCS, and ISS together
demonstrated a significant association (p < 0.05) with mortality (area under ROC
curve = 95%). Multiple linear regression established that blood pressure, heart
rate, temperature, hematocrit, and ISS had a collective significant effect (p <
0.05) on total blood product utilization explaining 67% of the variance in this
outcome variable. CONCLUSION: Admission physiology and injury characteristics
demonstrate a strong capacity to predict resource utilization in the contemporary
battlefield environment. In the future, such predictive yield could potentially
have significant implications for triage and medical logistics in the resource
constrained environment of war and potentially in mass casualty and disaster
incidents in the civilian trauma setting which will likely have mechanistic
similarity with war related injury.
PMID- 17033547
TI - Tactical surgical intervention with temporary shunting of peripheral vascular
trauma sustained during Operation Iraqi Freedom: one unit's experience.
AB - BACKGROUND: Rapidly restoring perfusion to injured extremities is one of the
primary missions of forward military surgical teams. The austere setting, limited
resources, and grossly contaminated nature of wounds encountered complicates
early definitive repair of complex combat vascular injuries. Temporary vascular
shunting of these injuries in the forward area facilitates rapid restoration of
perfusion while allowing for deferment of definitive repair until after transport
to units with greater resources and expertise. METHODS: Standard Javid or Sundt
shunts were placed to temporarily bypass complex peripheral vascular injuries
encountered by a forward US Navy surgical unit during a six month interval of
Operation Iraqi Freedom. Data from the time of injury through transfer out of
Iraq were prospectively recorded. Each patient's subsequent course at Continental
US medical centers was retrospectively reviewed once the operating surgeons had
returned from deployment. RESULTS: Twenty-seven vascular shunts were used to
bypass complex vascular injuries in twenty combat casualties with a mean injury
severity score of 18 (range 9-34) and mean mangled extremity severity score of 9
(range 6-11). All patients survived although three (15%) ultimately required
amputation for nonvascular complications. Six (22%) shunts clotted during
transport but an effective perfusion window was provided even in these cases.
CONCLUSION: Temporary vascular shunting appears to provide simple and effective
means of restoring limb perfusion to combat casualties at the forward level.
PMID- 17033548
TI - Long term impact of damage control surgery: a preliminary prospective study.
AB - BACKGROUND: To evaluate the impact of damage control laparotomy on long term
morbidity and survival. METHODS: Prospective data were collected on 56
consecutive trauma patients over a 20-month period (May 2000-January 2002).
Patients were stratified by mechanism of injury, age, Injury Severity Score, and
type of injury, temperature at admission, initial blood transfusion volume and
pH. Initial outcome data included major complications, intensive care unit and
hospital length of stay, and mortality. Readmission data including number of
admissions, surgical procedures, and hospital length of stay were then analyzed
over the subsequent follow-up years (2001-2003). RESULTS: The mean age of the
study group was 31 +/- 11 years with a mean Injury Severity Score of 33 +/- 13.
The majority of the patients were male (73%) with a relatively equal number of
blunt (n = 30) and penetrating injuries (n = 26). Liver injuries (34 [61%]) were
the most common solid organ injury followed by 22 bowel (39%), 19 spleen (34%),
11 major vessel (20%), and 7 pancreas (13%) injuries. The mean number of initial
abdominal surgical procedures was 4.4 +/- 2.2 per patient. The overall mortality
during the first admission was 27%. Time spent in the intensive care unit and
hospital length of stay was 17 +/- 13 and 30 +/- 19 days, respectively. There
were a total of 74 readmissions and 58 subsequent surgical procedures in the 41
patients who were readmitted. Thirty-one (76%) patients were re-admitted at least
one time. Infection (n = 19) was the most common reason for readmission followed
by ventral hernia repair (n = 17) and fistula management (n = 14). There was 0%
mortality for patients who survived the preliminary hospitalization but required
readmission. CONCLUSION: Although damage control laparotomy is associated with a
significant complication and readmission rate, its long term survival and benefit
is indisputable.
PMID- 17033549
TI - High frequency oscillatory ventilation for surgical patients with acute
respiratory distress syndrome.
AB - BACKGROUND: Numerous studies have suggested that high-frequency oscillatory
ventilation (HFOV) used as rescue therapy may improve oxygenation in acute
respiratory distress syndrome (ARDS) patients. The purpose of this study is to
analyze the efficacy and safety of HFOV in surgical patients with ARDS. METHODS:
A total of 16 surgical ARDS patients with severe oxygenation failure received
HFOV, despite aggressive conventional mechanical ventilatory support. Mean airway
pressure was initially set 3 to 5 cm H2O higher than that for conventional
ventilation and was subsequently adjusted to maintain oxygen saturation > or =
90% and FiO2 < or =0.6. Oxygenation, ventilation, and hemodynamic parameters were
measured during conventional ventilation before initiating HFOV and during HFOV
support for a total of 40 hours. Other outcome measures included duration of
HFOV, successful weaning rate, cause of failure, complications, survival rate,
and cause of death. RESULTS: There was a considerable increase in Pao2/FiO2 ratio
after 30 minutes, and this increase was maintained after 12 hours of HFOV
throughout the study. There was a significant decrease in oxygenation index after
24 hours of HFOV support. There was no significant change in blood pressure
associated with initiation and administration of HFOV. The successful weaning
rate from HFOV to conventional ventilation was 75%. The intensive care unit
survival rate was 43.8% and hospital survival rate was 37.5%. CONCLUSION: High
frequency oscillatory ventilation was effective and safe in correcting
oxygenation failure associated with ARDS in surgical patients. Future research is
warranted to identify the suitable patients, timing, and optimal strategy for
applying HFOV.
PMID- 17033550
TI - Evaluation of invasive and noninvasive hemodynamic monitoring in trauma patients.
AB - OBJECTIVES: The aim of this study was to compare a recently developed and
improved noninvasive hemodynamic monitoring system with the conventional invasive
monitoring by pulmonary artery catheterization (PAC) in acute emergency trauma
patients. METHODS: In a large, university-run, inner city public hospital, we
monitored 993 trauma patients noninvasively; 262 of these were simultaneously
monitored with both noninvasive hemodynamic and invasive PAC monitoring. The
noninvasive monitoring was begun shortly after admission to the emergency
department and the invasive PAC monitoring was started in the operating room, or
as soon as the patient arrived in the intensive care unit. Noninvasive monitoring
included cardiac index (CI) by the IQ or Physio Flow bioimpedance device,
together with mean arterial blood pressure, heart rate, pulse oximetry (SapO2),
transcutaneous oxygen (PtcO2), and carbon dioxide (PtcCO2) tensions. We compared
CI by simultaneous measurements with both invasive and noninvasive methods 907
times in 262 patients. RESULTS: The CI by thermodilution (CItd) correlated well
with simultaneous measurements with the bioimpedance (CIbi), r2 = 0.915, r2 =
0.84, p < 0.001. The bias and precision of simultaneous measurements was -0.070
+/- 0.47 L/min/m2; agreement was considered satisfactory. In the initial
resuscitation period of both monitoring systems, the CI, mean arterial blood
pressure, SapO2, and tissue perfusion (reflected by invasive DO2 and VO2, and by
noninvasive PtcO2/FiO2 ratio) were higher in survivors than in nonsurvivors,
whereas heart rate values were higher in the nonsurvivors. We concluded that
noninvasive hemodynamic monitoring provided a feasible, safe, inexpensive,
accurate, continuous, on-line real-time graphic displays that are equivalent to
the essential features of invasive pulmonary artery catheter monitoring.
PMID- 17033551
TI - Biomechanic study of the human liver during a frontal deceleration.
AB - BACKGROUND: Mechanisms of hepatic injury remain poorly understood. Surgical
literature reports some speculative theories that have never been proved. The aim
of this study was to examine the behavior of the liver during brutal frontal
deceleration. METHODS: Six trunks, removed from human cadavers, underwent free
falls at 4, 6, and 8 meters per second (mps). Accelerometers were positioned in
the two lobes of the liver, in front of the vertebra L2, and in the retro hepatic
inferior vena cava. Relative motions of the lobes of the liver and of the two
other anatomic marks were observed. In parallel, numerical simulations of this
experiment have been performed using a finite element model. RESULTS: In the
direction of impact, the vertebra L2 had no considerable displacement with the
inferior vena cava. There was a noteworthy displacement between the two hepatic
lobes. The left hepatic lobe had a large relative displacement with the vertebra
L2 and the inferior vena cava. The right hepatic lobe was more stable with the
vertebra L2 and the inferior vena cava. Numerical simulation of the same protocol
underlined a rotation effect of the liver to the left around the axis of the
inferior vena cava. CONCLUSIONS: These results support the surgical data. They
highlight a crucial zone and explain how dramatic lacerations between the two
lobes of the liver can occur.
PMID- 17033552
TI - A prospective evaluation of the value of repeat cranial computed tomography in
patients with minimal head injury and an intracranial bleed.
AB - BACKGROUND: Patients with minimal head injury (MHI) and intracranial bleed (ICB)
detected on cranial computed tomography (CT) scan routinely undergo a repeat
cranial CT within 24 hours after injury to assess for progression of intracranial
injuries. While this is clearly beneficial in patients with a deteriorating
neurologic status, it is of questionable value in patients with a normal
neurologic examination. The goal of this study was to prospectively assess the
value of a repeat cranial CT in patients with a MHI and an ICB who have a normal
neurologic examination. METHODS: A prospective analysis of all adult patients
admitted to a Level I trauma center after blunt trauma causing a MHI (defined as
the loss of consciousness or posttraumatic amnesia with a Glasgow Coma Scale
(GCS) score of greater or equal to 13) and an ICB on the initial cranial CT
during a 12-month period (July 2002 through July 2003) was performed. All
patients with MHI were prospectively evaluated and followed until discharge. Data
collected included demographics, neurologic examination and findings on the
initial and repeat cranial CT scan. Outcome data included neurologic
deterioration, neurosurgical intervention, and Glasgow Outcome Scale (GOS) on
discharge. RESULTS: In all, 161 consecutive patients with MHI and a positive
cranial CT scan were identified. The initial cranial CT lead to a neurosurgical
intervention (1 craniotomy, 4 intracranial pressure monitors) in 4% of cases. The
remaining 130 patients who met inclusion criteria, underwent a repeat cranial CT
scan within 24 hours postadmission. Ninety nine (76%) patients had a normal
neurologic examination at the time of their repeat cranial CT. After the repeat
cranial CT none required immediate neurosurgical intervention or had delayed
neurologic deterioration related to their head injury. Fifteen patients underwent
additional neuroradiologic studies but none showed further progression of their
ICB or lead to a change in management. One patient died from non-traumatic brain
injury related causes and of the remaining 26 patients, 98% had an overall
favorable GOS score (> 3) on discharge. In this group of patients with MHI and
ICB, the negative predictive value of a normal neurologic examination was 100%.
CONCLUSIONS: Repeat cranial CT, in patients with a MHI and a normal neurologic
examination, resulted in no change in management or neurosurgical intervention
and is therefore not indicated. A multicenter prospective study would further
validate these conclusions, reduce unnecessary CT scans, and likely improve our
current standard of care in these patients.
PMID- 17033553
TI - Early prediction of mortality in isolated head injury patients: a new predictive
model.
AB - BACKGROUND: To construct a predictive model of survival in isolated head injury
patients, on the basis of easily available parameters that are independent risk
factors for survival outcome. METHODS: Trauma registry-based study of head injury
patients who had no other major extracranial injuries and were not hypotensive at
admission. A predictive model of probability of death was constructed using
discriminant analysis, on the basis of admission Glasgow Coma Scale (GCS) score,
head Abbreviated Injury Score (AIS), age, and mechanism of injury. RESULTS: The
study included 7,191 patients with head trauma. The overall correct
classification rate of the proposed predictive model was 94.2% as compared with
89.0% of the admission GCS score (p < 0.05) and 92.8% of the head AIS (p < 0.05).
The correct classification rate of the predictive model developed for the severe
head trauma (GCS score 4-8) patients was 79.9%, as compared with 72.6% using the
admission GCS score alone or 75.1% (p < 0.05). A one-page, easy to use table
summarizing the predicted mortality on the basis of GCS score, head AIS,
mechanism of injury, and age was developed. CONCLUSIONS: The proposed model has a
significantly better predictive power, especially in severe head trauma, than the
extensively used GCS and head AIS. A simple table on the probability of death of
a particular patient based on admission GCS score, head AIS, mechanism of injury
and age of patient can provide instant information.
PMID- 17033554
TI - Endothelin-1, inducible nitric oxide synthase and macrophage inflammatory protein
1alpha in the pathogenesis of stress ulcer in neurotraumatic patients.
AB - BACKGROUND: To prospectively identify histologically and endoscopically the
effect of omeprazole on the expression of endothelin-1 (ET-1), inducible nitric
oxide synthase (iNOS) and macrophage inflammatory protein-1alpha (MIP-1alpha) in
the gastric mucosa of neurosurgical patients with stress ulcer. METHODS: Twenty
five patients with severe acute intracranial lesions caused by trauma were
enrolled in this study. A 40 mg intravenous bolus of omeprazole (OME) was given
daily for 7 days. The intragastric pH was continuously recorded for 24 hours on
day 1 and 8. Endoscopic evaluation of the gastric corpus, antrum, and duodenal
bulb was performed in the ICU, within 24 hours after brain injury, and at follow
up on the 7th day after admission. Paired biopsies were obtained for histologic
examinations and immunohistochemical analysis was performed using a LSAB method
for MIP-1alpha, ET-1, and iNOS. RESULTS: There were 72% and 70% of gastroduodenal
mucosal lesions at the initial and follow-up endoscopies, respectively. However,
the severity of mucosal lesions showed significant improvement in most patients
at follow-up (p < 0.05). Mean percentages of time intragastric pH were greater
than or equal to 4.0 were 20 +/- 11% and 70 +/- 17% on day 1 and 8, respectively
(p < 0.05). The incidences of ET-1, iNOS and MIP-1alpha expression were not
significantly different between the patients before and after OME prophylaxis.
CONCLUSIONS: Prophylactic OME is effective in reducing the severity of stress
ulcerations in severe neurotraumatic patients. High incidence of tissue ET-1
expression combined with increased activity of iNOS and MIP-1alpha may be
responsible for the gastric mucosal injury. We also show that OME fails to
counter the enhancement in the mucosal expression of ET-1, iNOS, and MIP-1alpha
caused by severe brain damage.
PMID- 17033555
TI - Bradykinin B2 receptor antagonism with LF 18-1505T reduces brain edema and
improves neurological outcome after closed head trauma in rats.
AB - BACKGROUND: We evaluated the effect of LF 18-1505T, a novel nonpeptide bradykinin
type-2 receptor antagonist, on brain edema and neurologic severity score (NSS)
after closed head trauma (CHT). METHODS: There were 132 rats anesthetized and
assigned for sham or CHT; infusion of saline or LF 18-1505T (0.3, 1, 3, 10, or 30
microg x kg x min); and determination of neurologic outcome (brain water content
and NSS) or physiologic variables (blood pressure, glucose concentration, etc.).
RESULTS: Post-CHT brain water content was less with LF 18-1505T doses of 3 and 10
microg x kg x min (80.1 +/- 3.8 through 81.6 +/- 2.6%, mean +/- SD) than in the
untreated group (84.6 +/- 1.9%, p < 0.01). Post-CHT NSS improved with doses of 3,
10, and 30 microg x kg x min (median, 7; range, 0-12 through median, 10; range, 8
18) as compared with that in the untreated group (median, 17; range, 14-23; p <
0.05). LF 18-1505T with or without CHT did not significantly alter physiologic
variables. CONCLUSIONS: LF 18-1505T decreased brain edema and improved neurologic
status after CTH in rats without significantly altering physiologic values.
PMID- 17033556
TI - Long-term follow-up of Iranian veteran upper extremity amputees from the Iran
Iraq war (1980-1988).
AB - BACKGROUND: Despite their frequency, there are limited reports concerning long
term follow up of upper limb amputation among battle-injured patients, which
occurred at a young age. The purpose of this study was to evaluate how well these
patients function years after their injury. METHODS: The study consisted of a
thorough assessment and examination and review of the history and war time
medical records of 25 Iranian veteran amputees from imposed Iran-Iraq war with a
comprehensive survey including a detailed questionnaire. Information was analyzed
and compared with limited similar reports in the literature. RESULTS: Out of 200
war amputees there were 25 unilateral upper limb amputees; all others were lower
limb amputees. The average age at the time of injury was 23.06 years, average age
at follow-up was 41.55 years, and the average time between injury and follow-up
was 17.5 years. The most common level of amputation was below elbow (40%), and
the most common cause of war injury was artillery shells, mortar or rocket
shells. The prevalence of clinical symptoms of phantom sensation, phantom pain,
phantom movement and stump pain were; 64%, 32%, 20%, 24%, respectively. All
patients were married (100%) and had children except one case (96%). Sixty
percent of patients were employed. Thirty-six percent had a documented
psychiatric history ranging from minor depression to posttraumatic stress
disorders. CONCLUSION: The study showed-despite long period of time between war,
amputation, and follow-up-there is a significant rate of amputation symptoms, but
on the other hand good family and social function of the patients.
PMID- 17033557
TI - Results of total elbow arthroplasty in the treatment of distal humerus fractures
in elderly Asian patients.
AB - BACKGROUND: Distal humerus fractures in elderly patients are difficult to treat
as these fractures are often complicated by varying degrees of comminution intra
articular involvement and osteoporosis. We retrospectively reviewed the results
of primary total elbow arthroplasty in the treatment of distal humerus fractures
in seven patients followed for a minimum of 1 year. METHODS: Between July 2000
and June 2002, seven patients with distal humerus fractures were treated
electively with total elbow arthroplasty using the semiconstrained Coonrad-Moorey
elbow replacement prostheses. The Mayo Elbow Performance Score was used to assess
the outcomes. RESULTS: The mean age of our patients was 72.9 years. The mean
duration of postoperative hospitalization stay was 7.6 days. The average length
of follow up was 24.9 months. Six of these patients had no pain, and one patient
had mild pain. The mean arc of flexion was 88.6 degrees. Six elbows had excellent
results, while 1 elbow had good result. The mean Mayo score was 94.3 points. One
elbow developed blisters postoperatively but resolved with dressings and
antibiotics. CONCLUSIONS: Our review suggests that total elbow arthroplasty can
give good to excellent short term results when used in the treatment of distal
humerus fractures in elderly Asian patients.
PMID- 17033558
TI - Effectiveness of completely round nails with both-ends-threaded locking screws
for tibial shaft fractures.
AB - BACKGROUND: Completely round nails, in contrast to conventional locked nails with
surface grooves, for postoperative endosteal revascularization may increase the
nail rigidity and decrease the manufacture cost. Both-ends-threaded screws with
higher fatigue strength require smaller nail holes and can further increase the
mechanical strength of the nails. METHODS: In this study, both-ends-threaded
locking screws were used to treat 68 tibial fractures, including 56 acute
fractures in 54 patients and 12 nonunions in 12 patients. There were 41 men and
25 women with a mean age of 39.6 years, and the average follow-up was 24 months.
For acute fractures, there were 11 type I, 9 type II, 5 type IIIA, and 3 type
IIIB open fractures. Acute fractures were treated with closed nailing. Five
hypertrophic nonunions were treated with closed exchanged nailing, and seven
oligotrophic nonunions were treated with open nailing and iliac bone grafting.
RESULTS: With a single nailing procedure, 53 acute fractures and all nonunions
achieved union with mean times of 17.4 weeks and 18.4 weeks, respectively. Three
patients underwent exchange nailing and bone grafting and had eventual fracture
union. Three fractures with compartment syndrome were treated with fasciotomy.
Deep infection occurred in two open fractures but was successfully treated. Nail
breakage occurred in one distal fracture and screw backout occurred in another,
but fracture union was not affected. Recovery of joint motion was essentially
normal in patients without knee or ankle injury. CONCLUSIONS: This study showed
that completely round nails with both-ends-threaded locking screws could
effectively treat tibial fractures. Completely round nails have the advantages of
high mechanical strength and low manufacturing cost.
PMID- 17033559
TI - Overdistraction of the fracture eases reduction in delayed femoral nailing:
results of intraoperative force measurements.
AB - BACKGROUND: (Initial) primary external fixation of femoral shaft fractures
followed by secondary intramedullary nailing is a concept of damage control
orthopedics. We hypothesized that external fixation with overdistraction of the
fracture might reduce reduction forces and shorten reduction time during the
secondary nailing. METHODS: An experimental study on seven patients with eight
fractures of the femoral shaft was conducted. Intraoperative reduction forces
were determined in all patients using a load cell. The amount of distraction was
measured on the latest radiographs before nailing. The reduction time was
recorded as an indirect indicator of the intricacy of reposition. Reduction
forces and reduction times were compared between those fractures fixed with
shortening (Group A) and those fixed in distraction (Group B). RESULTS: Three
femurs showed some shortening and five femurs showed some distraction within the
fracture. The maximum measured distraction force along the shaft axis was 396 N.
On average the maximal force was 336 N (+/- 51.9 N) in Group A and 200 N (+/-
43.1 N) in Group B. This difference is statistically significant (p = 0.007). The
average reduction time was 28.3 minutes (+/- 21.8 minutes) in Group A and 5.8
minutes (+/- 4.0 minutes) in Group B. This difference shows a trend toward
significance (p = 0.056). CONCLUSION: Fracture shortening leads to higher
restraining forces and consequently prolonged reduction time in delayed nailing.
Overdistraction should be performed as soon as possible under careful soft-tissue
monitoring.
PMID- 17033560
TI - Three-dimensional analysis of pelvic volume in an unstable pelvic fracture.
AB - BACKGROUND: A model was developed to predict changes in pelvic volume associated
with increasing pubic diastasis in unstable pelvic fractures. METHODS: Intact and
postfracture pelvic volumes were calculated in 10 cadavers using computerized
axial tomography (CT). The true pelvis was assumed to be either a sphere, a
cylinder, or a hemi-elliptical sphere. Using the appropriate equations for
calculating the volume of each of these shapes, pelvic volume was predicted and
then compared with the measured values. RESULTS: The observed volume changes
associated with increasing pubic diastasis were much smaller than previously
reported. The mean difference between the measured and predicted volume was 20.0
+/- 9.9% for the sphere, 10.7 +/- 6.5% for the cylinder, and 4.5 +/- 5.9% for the
hemi-elliptical sphere. The differences between these means were statistically
significant (p < 0.001). CONCLUSIONS: This data suggests that the hemi-elliptical
sphere best describes the geometric shape of the true pelvis and better predicts
quantitative changes in pelvic volume relative to an increasing pubic diastasis
as the radius has little effect on the change in volume. Due to the small changes
in volume observed with increasing diastasis, factors other than the absolute
change in volume must account for the clinically observed effects of emergent
pelvic stabilization.
PMID- 17033561
TI - Compartment pressures, limb length changes and the ideal spherical shape: a case
report and in vitro study.
AB - BACKGROUND: Changes in compartment pressures have been noted during traction,
reduction, and intramedullary fixation of fractures. Changes in limb length and
compartment volumes are suspected contributing factors. Pressure and volume
changes are known to be related in animal models. If an acute increase in limb
length can adversely affect compartment pressures, reversal or delay of such an
increase in length may be of value in the treatment and prevention of compartment
syndromes. METHODS: A clinical example is presented in which a documented
anterior compartment syndrome was successfully treated by deliberate loss of
fracture reduction, without fasciotomy. Fracture reduction was later restored
when swelling subsided. Anterior compartment pressures were recorded in response
to limb length changes in osteotomized cadaver limbs stabilized with external
fixation. RESULTS: The pressure in the anterior compartment varies directly with
acute changes in the length of the leg, in an experimental model. Mathematical
analysis indicates that available volume within a compartment varies inversely
with acute changes in its length. CONCLUSIONS: Fracture reduction that restores
the length of an acutely injured extremity may increase pressure in the
compartments by decreasing available volume. Deliberate loss of reduction can
decrease pressure in the compartments, offering a potential alternative to
fasciotomy in the care of compartment syndrome in cautiously selected, monitored
patients. Early stabilization without reduction, followed by delayed reduction,
may be preferable during treatment of fractures prone to compartment syndrome.
Decreased available compartment volume may contribute to compartment syndrome
after distraction with intramedullary rods or skeletal traction.
PMID- 17033562
TI - Hyperbaric oxygen therapy in orthopedic conditions: an evaluation of safety.
AB - BACKGROUND: Because of the documented cellular and biochemical benefits of
hyperbaric oxygen (HBO), HBO therapy is applied now with increasing frequency to
various orthopedic conditions. Many traumatologists and orthopedic surgeons might
refer their patients for adjuvant HBO therapy. However, the potential risks and
risk-benefit ratio have often been underemphasized in therapeutic trials.
METHODS: From October 2002 to September 2004, 240 patients with a total of 4,638
treatments received HBO therapy at the hyperbaric medicine center of our
institution on an identical treatment protocol. HBO therapy patient treatment
logs were reviewed to analyze the incidence of complications during HBO
treatment. RESULTS: The overall incidence of complications was 1.83%. Over 94% of
treatment complications were mild to moderate and designated as minor
complications; fewer than 6% were severe or life threatening and designated as
major complications. The incidence of major complications (central nervous system
[CNS] oxygen toxicity in this series) was 0.109%. There was no mortality. Two
patients with unusual presentation of CNS oxygen toxicity were observed during
the study period. CONCLUSIONS: HBO therapy in orthopedic conditions is considered
as a safe treatment because of a very low complication rate; however, analysis of
patients with CNS oxygen toxicity revealed its unpredictability and
inevitability. Although it is common sense that patients who develop a seizure in
the hospital need help from the medical staff, it cannot be done in a monoplace
hyperbaric chamber because of pressure unequalization. Therefore, a multiplace
chamber equipped with an antechamber for medical contingency is possibly the
better facility in consideration of safety.
PMID- 17033563
TI - The effect of hypoxemic resuscitation of hemorrhagic shock on hemodynamic
stabilization and inflammatory response: a pilot study in a rat experimental
model.
AB - BACKGROUND: Resuscitation of hemorrhagic shock is associated with tissue injury.
The effect of hypoxemia during resuscitation was investigated. METHODS: Shock was
induced by withdrawing blood to mean arterial pressure (MAP) 40 mm Hg and
maintained for 60 minutes in 25 Wistar rats. Animals were randomly divided to
receive either normoxemic (controls, FiO2 = 21%, n = 14) or hypoxemic (HypRes,
FiO2 = 12%, n = 11) resuscitation by re-infusing their shed blood. Outcome was
assessed through hemodynamic and inflammatory parameters. Another nine rats
served to correlate different FiO2 to the corresponding PaO2. RESULTS: At 60
minutes of resuscitation HypRes had higher MAP than control animals (p = 0.008).
The respective median (range) malondialdehyde and TNF-alpha levels was 1.7 (1
2.1) versus 3.1 (2.4-4.3) micromol/L, (p = 0.02) and 0 versus 5.8 (0-5.8) pg/mL,
(p = 0.025). Glutathione, endotoxin, interferon-gamma, and nitric oxide values
were similar between groups. FiO2 of 12% induced only a mild hypoxemia (PaO2
approximately 80 mm Hg). CONCLUSIONS: Even mild hypoxemia during resuscitation of
shock leads to effective hemodynamic stabilization.
PMID- 17033564
TI - Impact of severity of local soft-tissue trauma on long-term manifestation of
microcirculatory and microlymphatic dysfunctions.
AB - BACKGROUND: The present study aimed at quantitatively evaluating the impact of
severity of local trauma on manifestation of soft-tissue injury-associated
microcirculatory and microlymphatic dysfunctions in a chronic model that allowed
repeated analyses by intravital fluorescence microscopy. METHODS: C57BL/6 mice
were chronically instrumented with dorsal skinfold chambers and subjected to mild
(180 J/m2, n = 6), moderate (270 J/m2, n = 6), or severe trauma (450 J/m2, n = 6;
540 J/m2, n = 6). Nontraumatized animals served as controls (sham; n = 8).
Intravital microscopy was performed before and at 5 minutes, 1 hour, 8 hours, 24
hours, 3 days, and 5 days after trauma, and included the analysis of (1) blood
and lymph microvessel rupture, (2) hematoma formation and lymph leakage, (3)
arteriolar and venular constriction, (4) capillary perfusion failure, (5)
arteriolar and venular leukocyte adhesion, and (6) interstitial edema formation.
RESULTS: Mild trauma did not induce any changes of microcirculatory and
microlymphatic functions. Moderate trauma did not affect lymphatics but provoked
arteriolar constriction, capillary perfusion failure, leukocyte-endothelial cell
interactions, and minor blood vessel ruptures with hematoma formation. These
alterations, however, recovered within the first 24 hours after trauma. Severe
trauma also did not affect the lymphatic microvasculature, but resulted in
massive hematoma formation, arteriolar constriction, and capillary perfusion
failure, which was associated with marked arteriolar and venular leukocyte
recruitment and edema formation, and which did not recover to normal over a 5-day
observation period. CONCLUSION: Only severe trauma of > 450 J/m2 provokes
irreversible microcirculatory dysfunction in soft tissue, however, without
affecting the integrity of lymphatic microvessels. Of interest, trauma-induced
microcirculatory alterations are neither dominated solely by microcirculatory
dysfunction nor by leukocytic inflammation. Instead, both pathologies develop in
parallel, generating a vicious circle, which may be responsible for the
compromised healing of severely traumatized soft tissue frequently observed in
clinical practice.
PMID- 17033565
TI - Lung injury and recovery after exposure to blast overpressure.
AB - BACKGROUND: A critical immediate determinant of survival after exposure to blast
overpressure (BOP) is pulmonary damage, but mechanisms of injury and the course
of recovery are not well understood. The objective of this study was to
characterize the progression of oxidative and inflammatory responses in lungs as
well as the activation of consequent protective mechanisms after exposure to
medium intensity BOP. METHODS: Rats were exposed to a moderate (approximately 120
kPa) level of BOP in a pneumatically driven shock tube. At different times (2-192
hours) after exposure, lungs were examined for pathologic signs of injury,
markers of inflammatory responses, and indicators of oxidative and nitrative
damage. RESULTS: The results showed a postblast activation of inflammatory
response (increase of myeloperoxidase activity, CINC-1, ICAM-1, and iNOS),
increase in protein oxidation and nitration, and development of gross diffused
hemorrhage in lungs. The initial phase of lung damage that peaked at 24 to 48
hours after exposure to BOP was followed by gradual dissolution of inflammation
and oxidation that were complete by 192 hours. Resolution of morphologic damage
and inflammation in lungs concurred with activation of expression of antioxidant
enzymes heme oxygenase-1 (HO-1) and manganese superoxide dismutase (MnSOD).
Plasma level of gelsolin, a marker of acute lung damage was decreased at 24 hours
postblast and later returned to the control level. CONCLUSIONS: The study shows
the role of adaptive anti-oxidant and anti- inflammatory mechanisms in lung
recovery after injury caused by exposure to BOP.
PMID- 17033566
TI - Simulation training for a mass casualty incident: two-year experience at the Army
Trauma Training Center.
AB - BACKGROUND: Civilian and military mass casualty incidents (MCI) are an
unfortunate reality in the 21st century, but there are few situational training
exercises (STX) to prepare for them. To fill this gap, we developed a MCI STX for
U.S. Army Forward Surgical Teams (FST) in conjunction with the U.S. Army Trauma
Training Center. METHODS: After a standardized briefing, each FST has 60 minutes
to unpack, setup, and organize a standard equipment cache into an emergency room,
operating room, and intensive care unit. In an adjacent room, five anesthetized
swine are prepared with standardized, combat-relevant injuries. The number and
acuity of the total casualties are unknown to the FST and arrive in waves and
without warning. A realistic combat environment is simulated by creating resource
limitations, power outages, security breaches, and other stressors. The STX
concludes when all casualties have died or are successfully treated. FSTs
complete a teamwork self-assessment card, while staff and FST surgeons evaluate
organization, resource allocation, communication, treatment, and overall
performance. Feedback from each FST can be incorporated into an updated design
for the next STX. RESULTS: From 2003-2005, 16 FSTs have completed the STX. All
FSTs have had collapses in situational triage, primary/ secondary surveys, and/or
ATLS principles (basic ABCs), resulting in approximately 20% preventable deaths.
CONCLUSIONS: We concluded (1) a MCI can overwhelm even combat- experienced FSTs;
(2) adherence to basic principles of emergency trauma care by all FST members is
essential to effectively and efficiently respond to this MCI; (3) by
prospectively identifying deficiencies, future military or civilian performance
during an actual MCI may be improved; and (4) this MCI STX could provide a
template for similar programs to develop, train, and evaluate civilian surgical
disaster response teams.
PMID- 17033567
TI - Do trauma centers have the capacity to respond to disasters?
AB - BACKGROUND: Concern has been raised about the capacity of trauma centers to
absorb large numbers of additional patients from mass casualty events. Our
objective was to examine the capacity of current centers to handle an increased
load from a mass casualty disaster. METHODS: This was a cross-sectional study of
Level I and II trauma centers. They were contacted by mail and asked to respond
to questions about their surge capacity as of July 4, 2005. RESULTS: Data were
obtained from 133 centers. On July 4, 2005 there were a median of 77 beds
available in Level I and 84 in Level II trauma centers. Fifteen percent of the
Level I and 12.2% of the Level II centers had a census at 95% capacity or
greater. In the first 6 hours, each Level I center would be able to operate on 38
patients, while each Level II center would be able to operate on 22 patients.
Based on available data, there are 10 trauma centers available to an average
American within 60 minutes. Given the available bed capacity, a total of 812 beds
would be available within a 60-minute transport distance in a mass casualty
event. CONCLUSIONS: There is capacity to care for the number of serious non
fatally injured patients resulting from the types of mass casualties recently
experienced. If there is a further continued shift of uninsured patients to and
fiscally driven closure of trauma centers, the surge capacity could be severely
compromised.
PMID- 17033568
TI - Primary trauma diversion: initial experience in Hong Kong.
AB - BACKGROUND: Trauma is a leading cause of death and loss of workdays in Hong Kong.
Reports have suggested that timely provision of care in dedicated trauma centers
can improve outcomes. Until recently, ambulances were required to take trauma
patients to the nearest hospital's emergency department. This paper reports on
the initial experience of primary trauma diversion from scene to a dedicated
trauma center in Hong Kong. METHODS: This prospective study involved the
establishment of primary trauma diversion in the area served by Alice Ho
Nethersole Hospital (AHNH), a general hospital in the New Territories. Trauma
patients who fulfilled diversion criteria were taken directly to the Prince of
Wales Hospital (PWH) in Shatin, a university teaching hospital and trauma center
for the area. Data were collected to determine the change in time to definitive
care for trauma patients and an impact analysis on PWH services was performed.
RESULTS: There were 60 patients who underwent primary trauma diversion and 35
patients underwent secondary diversion after initial treatment at AHNH. This
represented two extra trauma patients per week at PWH. Median Injury Severity
Score (ISS) was 9 and 52% of patients had been involved in a traffic crash. Of
eligible patients, 76% (69 out of 91) diverted correctly according to protocol.
Primary trauma diversion patients reached definitive care 97 minutes faster than
patients undergoing secondary diversion. CONCLUSION: Primary trauma diversion is
feasible in Hong Kong and means that patients reach definitive care 97 minutes
faster than going to the nearest hospital. Primary trauma diversion protocols
should be extended throughout Hong Kong.
PMID- 17033569
TI - Impaired generic health status but perception of good quality of life in
survivors of burn injury.
AB - BACKGROUND: Although it is recognized that burn survivors face a variety of
challenges related to physical, psychologic and social late-effects of their
injury, the impact of thermal injury on the lives of patients is not fully
understood. To learn more about burn patient needs and to obtain information
relevant to the design of clinical programs for treatment and aftercare, self
reports on how burn patients perceive their health and quality of life may be of
significant value. METHODS: The generic health status (evaluated by SF-36) and
overall quality of life (evaluated by the Quality of Life Scale [QOLS]) of 95
adult burn patients (total body surface area burned = 18.5 +/- 14.2% [mean +/-
SD]; 82.1% men) were assessed 47.0 +/- 23.8 months postburn and compared with
population norms. RESULTS: The burn patient generic health status was
significantly poorer than expected from general population scores, with reduced
scores in the Physical Function (p < 0.001), Role Physical (p < 0.01), General
Health (p < 0.001), Social Function (p < 0.001), and Role Emotional (p < 0.001)
domains of the SF-36. Despite their reduced health status, overall quality of
life was perceived as good, with QOLS scores similar to those of the general
population. Patients living alone, unemployed, having nonburn physical illness,
psychologic disorders, chronic pain, or having sustained full thickness injuries
were found to be at particular risk. CONCLUSIONS: Forty-seven months postinjury,
burn patients still experienced a significant reduction of generic health,
reporting limitations related to both physical and psychosocial SF-36 domains. On
the other hand, the patients as a group reported overall quality of life similar
to that of the norm population, suggesting that they were able to feel
satisfaction with their new situation of life. Identification of several risk
factors for reduced generic health status and overall quality of life support the
need for specialized multidisciplinary aftercare for burn patients.
PMID- 17033570
TI - Chirurgica Taurina: a 10-year experience of bullfight injuries.
AB - BACKGROUND: Despite recent efforts to improve medical treatment for injured
bullfighters, including the foundation of a scientific society for bullfight
injuries, serious injuries, in particular in villages and smaller arenas, still
do occur. We are not aware of any series in the English literature that aimed to
study the specific mechanisms, types, and outcomes of these injuries. METHODS: A
review of the trauma registry of injured bullfighters who suffered any type of
trauma during bullfighting and received emergency therapy by the Surgical Trauma
Services between 1994 and 2004 at the Plaza de Toros Nuevo Progreso, Guadalajara,
Mexico. RESULTS: In all, 68 out of 750 bullfighters (9.06%) required emergency
assistance during bullfighting. Trauma to the upper and lower extremity was most
common (66%), followed by injuries to the inguinal (8%) and perineal area (7%).
Extremity injuries included penetrating wounds requiring operative debridement in
64% of cases, articular dislocations in 4%, closed fractures in 4%, and open
fractures in 1% of cases. Major vascular injuries occurred in 5% of the cases.
Penetrating inguinal and penetrating perineal injuries were associated with major
vascular injuries to the femoral vessels, necessitating operative repair in 33%
of the cases. CONCLUSION: A considerable risk of serious, life-threatening
injuries is inherent to bullfighting. Penetrating inguinal and perineal trauma
with injury to the femoral vessels represents a specific, potentially fatal
injury. A low threshold for exploration of these penetrating injuries in injured
bullfighters is associated with a favorable outcome. Appreciation of the unique
mechanisms and types of injuries related to bullfighting should lead to target
intervention and help the evolvement of improved emergency treatment in organized
bullfighting.
PMID- 17033571
TI - Accidental foot burns in children from contact with naturally heated surfaces
during summer months: experience from a regional burn center.
AB - BACKGROUND: Foot burns in children often result from contact with heated surfaces
due to high ambient temperatures during summer in the southwestern United States.
The objective of this study was to describe the unique cause and clinical
characteristics of this type of injury. METHODS: A retrospective review of
medical records of pediatric patients presenting with contact burns of the foot
in Arizona Burn Center, which is the third largest burn center in the United
States. Participants included children 5 years and under who were treated for
pedal burns during a 5-year period between January 2000 and August 2005. RESULTS:
Seventy-four children with contact burns of the foot were treated of which 34
(46%) were from naturally heated surfaces. When compared with those who sustained
pedal burns as a result of contact with other hot objects, children with burns
from naturally heated surface more commonly had bilateral (82.4%), second degree
(82.4%) burns involving primarily the plantar surface (94.1%) of the foot and the
injury usually occurred in the peak of the summer. Also, physical abuse was more
commonly suspected in this group. CONCLUSION: Contact with a hot surface during
summer months is a dominant cause of foot burns in small children in the
southwestern United States with characteristic clinical presentation and calls
for preventive educational interventions.
PMID- 17033572
TI - Aortic rupture in high-speed skiing crashes.
AB - BACKGROUND: New equipment and techniques in winter sports, such as carving skis
and snowboards, have brought up new trauma patterns into the spectrum of leisure
trauma. The injuries resemble high-energy trauma known from road crashes. The aim
of the present study was to assess the incidence of acute traumatic descending
aortic rupture in recreational skiing-crashes. MATERIAL: Between January 1995 and
December 2004, 22 patients were admitted to our hospital for aortic rupture. Four
patients had skiing crashes (18.2%). Mean age was 31 years, all patients were
male. In two cases, aortic rupture was associated with fractures of the upper and
lower extremities. One patient additionally had a cerebral contusion with an
initial Glasgow Coma Scale score of 13. In two patients, isolated aortic rupture
was diagnosed. RESULTS: Two patients were treated by graft interposition, and one
by endograft. One patient arrived under mechanical resuscitation without blood
pressure. He died at admission. He had been observed for 5 hours in another
hospital, complaining of severe intrascapular back pain, before transport to our
trauma unit for unknown bleeding. In the other three cases, treatment was
successful. CONCLUSION: Rescue services and paramedics should be aware of this
new type of injury. Acute aortic rupture has to be considered as possible injury
in high velocity skiing crashes.
PMID- 17033573
TI - Damage control surgery prior to organ harvesting.
PMID- 17033574
TI - Cause of post-traumatic hydrocephalus because of traumatic aqueduct obstruction
in two cases.
PMID- 17033575
TI - Relapsing altered mental status secondary to a meprobamate bezoar.
PMID- 17033576
TI - Hemorrhage into a pancreatic lymphangioma after blunt trauma mimicking a post
traumatic pancreatic pseudocyst.
PMID- 17033577
TI - Massive traumatic extrapleural hematoma mimicking hemothorax: a potential pitfall
of penetrating chest trauma.
PMID- 17033578
TI - Laryngeal injuries from a full face helmet: a report of two cases.
PMID- 17033579
TI - Safety belt use by law enforcement officers on reality television: a missed
opportunity for injury prevention?
AB - BACKGROUND: Although safety belt usage rates are increasing nationwide, motor
vehicle crashes (MVCs) remain a leading cause of death for young people and are
emerging as a leading cause for police officers specifically. A content analysis
was performed on the television show, COPS, to determine on-air safety belt usage
rates. METHODS: A sample of 63 unique episodes of the reality-based television
series, COPS, was viewed during a 4-month period (September 1, 2005 to January 1,
2006). Episodes had original airing dates ranging from 1990 to 2004. Safety belt
usage status was determined per police officer per driving scene (N = 250). A
driving scene represented a continuous trip (start to finish) with a total on
camera time exceeding 5 seconds. Scenes with indeterminate safety belt status
were excluded. High-speed driving, officer gender, and officer race were also
recorded. RESULTS: Of the 203 scenes included, 77 (38%) demonstrated safety belt
usage. High-speed driving scenes had higher safety belt usage rates compared with
low-speed (48% versus 29%, p = 0.005). More contemporary episodes (1999 to 2004)
had higher safety belt usage rates as well (51% versus 28%, p = 0.001). Officer
gender and race revealed no significant differences in safety belt usage rates (p
= 0.930 and p = 0.900, respectively). CONCLUSIONS: In this popular, reality-based
television series, safety belt usage by police officers is extremely low. These
findings suggest the need to increase safety belt usage by police officers,
especially those filmed for television.
PMID- 17033580
TI - Surgical management of lower cervical spine fracture in ankylosing spondylitis.
PMID- 17033581
TI - Fixation of mesh in large flank hernias as a result of extensive muscular
avulsion from seatbelt injuries.
PMID- 17033582
TI - Blunt injury to the thyroid gland: proposed classification and treatment
algorithm.
AB - BACKGROUND: Traumatic hemorrhage of the thyroid gland is a rare injury with few
published case reports. Surgical and nonsurgical management have been advocated
but there is no consensus of opinion. METHODS: This study is a retrospective
review of published case reports including two own cases. A classification and an
algorithm for diagnosis and treatment of thyroid gland injuries is proposed.
RESULTS: A literature review reveals 16 case reports. Of these, 11 patients
underwent neck exploration for control of hemorrhage and resection of the
associated thyroid abnormality while 5 patients were conservatively managed. Of
note is the fact that 10 of the 16 patients (63%) had pre-existing thyroid
disease. These 10 patients constituted (91%) of the group requiring surgical
treatment. CONCLUSION: Our proposed classification and algorithm offers
management guidelines for this rather rare injury. Conservative treatment may be
successful in selected patients with lower grade injuries and without concomitant
thyroid disease.
PMID- 17033583
TI - Rescue treatment with recombinant factor VIIa is effective in patients with life
threatening bleedings secondary to major wound excision: a report of four cases.
AB - Major burn wound excision is associated with excessive perioperative blood loss.
Treatment of massive microvascular bleeding represents a special problem in the
burn setting, characterized by extensive damage at the capillary level, and
resulting in a profound blood loss; which together with the consumptive states
makes adequate replacement therapy with coagulation factors and platelets
difficult. We described our experience with rescue treatment with rFVIIa in four
patients undergoing major wound excision, developing life-threatening
perioperative bleeding, and not responding to conventional therapy. Hemostasis
was achieved within 15 minutes of intravenous rFVIIa administration, at a dose of
100 microg/kg, in all patients. No treatment-related adverse events, in
particular, no thromboembolic events were observed. We conclude that rFVIIa may
be an effective hemostatic treatment for patients undergoing major wound excision
developing life-threatening bleedings.
PMID- 17033584
TI - Isolated gastric injury after blunt abdominal trauma.
PMID- 17033585
TI - Hepatic artery avulsion secondary to blunt abdominal trauma.
PMID- 17033587
TI - Abdominal computed tomography and the placement of inferior vena caval filters.
PMID- 17033588
TI - Silver-coated dressing acticoat caused raised liver enzymes and argyria-like
symptoms in burn patient.
PMID- 17033589
TI - Improper use of the term "shrapnel".
PMID- 17033591
TI - Development and initial psychometric evaluation of the participation measure for
post-acute care (PM-PAC).
AB - OBJECTIVE: To evaluate a patient-reported participation measure constructed
within the framework of the International Classification of Functioning,
Disability, and Health. DESIGN: The Participation Measure for Post-Acute Care (PM
PAC) contains 51 items that assess participation in nine domains: mobility; role
functioning; community, social, and civic life; domestic life/self-care; economic
life; interpersonal relationships; communication; work; and education. Self
reported data were collected by interview with 395 noninstitutionalized
rehabilitation patients. Psychometric analyses were conducted to test assumptions
underlying the scaling and scoring of PM-PAC scales and to evaluate reliability
and validity. RESULTS: In general, analyses supported assignment of items to
hypothesized scales. However, the community, social, and civic life,
interpersonal relationships, and communication domains were highly correlated.
Item response theory models indicated that items were directed primarily at
people with worse than average limitations in participation than the average
patient in this rehabilitation sample. Test and retest scale scores did not
differ significantly (intraclass correlation coefficient range, 0.61-0.86).
Groups with more severe conditions scored worse on PM-PAC scales, as
hypothesized. CONCLUSIONS: PM-PAC is a promising new measure of patient-reported
participation as defined by the International Classification of Functioning,
Disability, and Health. Information about PM-PAC items from this study will be
useful in developing a computerized, adaptive measure of participation.
PMID- 17033592
TI - Prognostic factors of activity limitation and discharge destination after stroke
rehabilitation.
AB - OBJECTIVE: The aim of this study was to identify predictive variables related to
activity limitation and home destination of a large sample of first-time stroke
patients at discharge from a rehabilitation hospital. DESIGN: A multicenter
observational study was conducted among 1023 first-time stroke patients who were
admitted to 18 different Italian inpatient rehabilitation centers between
February 1999 and November 2000. Only 997 patients were considered eligible. At
admission, sociodemographic and clinical data were considered as independent
variables. The outcome measures evaluated the ability to become functionally
independent (independence gain [Barthel Index score > or =18]) at discharge and
home return. RESULTS: The study data suggest that independence gain is associated
with an earlier rehabilitation intervention, being male, and low or absent
cognitive deficit. Home return is associated with no indwelling bladder
catheterization, no dysphagia, and living with a companion (roommate or family
member) before the stroke. CONCLUSIONS: In postacute stroke rehabilitation, level
of cognitive impairment, bladder dysfunction and dysphagia, early diagnosis and
treatment, early rehabilitation intervention, and living status (whether the
person was residing with a companion before the stroke) are important criteria
for outcome measurement at the time of admission. These previous characteristics
will most certainly provide clinicians with useful information during the acute
phase.
PMID- 17033593
TI - Toward benchmarks for stroke rehabilitation in Ontario, Canada.
AB - OBJECTIVE: Canadian benchmarking data do not exist for stroke rehabilitation
services. This study used the FIM-function-related group (FIM-FRG) classification
system to group patients and to describe the outcomes within each group. The
intent was to begin to develop benchmarks for persons recovering from stroke in
Canadian rehabilitation facilities. DESIGN: 561 patients were stratified into the
nine categories of the FIM-FRG system. Length of stay (LOS), total FIM gain,
total FIM at discharge, and discharge location were described for each category.
RESULTS: Mean waiting time to rehabilitation admission was 29.7 days. Mean LOS
was 49.2 days. Mean admission and discharge total FIM ratings were 78.1 and
103.1, respectively. FIM gain ranged from 8 to 37. Seventeen percent of patients
were discharged to nursing homes, with rates ranging from a low of 0% (FRG 8 and
9) to a high of 60% (FRG 2). CONCLUSIONS: For the nine FIM-FRG groups, LOS was
considerably longer in the Canadian facility than in the United States, and total
FIM score at discharge was higher in Canada. This is likely related to
differences in the healthcare systems of the two countries and confirms the need
to develop benchmarks based on Canadian data.
PMID- 17033594
TI - Severe Dysphagia after botulinum toxin B injection to the lower limbs and lumbar
paraspinal muscles.
AB - We report a case of severe dysphagia in a 29-yr-old woman with cerebral palsy
after she was injected with botulinum toxin B to her lower limbs and lumbar
paraspinal muscles. Four days after the treatment, she developed difficulty
swallowing, more severe for solid foods than for liquids, accompanied by dry
mouth, blurred vision, and voice hoarseness. Fifteen days after the injection,
with worsening of her dysphagia, she was hospitalized. A laryngoscopic evaluation
revealed bilateral vocal cord paresis, and a modified barium swallow test
demonstrated delayed oral initiation, upper airway penetration, and no reflexive
cough. In the following days, she improved spontaneously and was discharged 12
days later when she re-acquired the ability to swallow solid foods. Her symptoms
resolved completely only 75 days after the injection. Although dysphagia is a
common side effect of botulinum injection in the neck, to our knowledge, this is
the first reported case of severe dysphagia after injection in a distant anatomic
site.
PMID- 17033595
TI - Adding challenge to performance-based tests of walking: The Walking InCHIANTI
Toolkit (WIT).
AB - OBJECTIVE: In this report, we provide a detailed description of and
reproducibility data on the 14 performance-based tests of lower limb function
included in the Walking InCHIANTI Toolkit, which were designed to mimic
challenging situations that are encountered while walking in daily life. DESIGN:
Five women and five men were randomly selected from each of the age strata, 65
74, 75-84, and > or =85 yrs, among those who received a functional evaluation in
the Greve site at the second InCHIANTI study follow-up (total n = 30). Walking
tests were administered twice at 2-wk intervals. Analyses were aimed at assessing
reproducibility of the Walking InCHIANTI Toolkit components and the existence of
a learning effect. RESULTS: Performance remained stable for eight walking tests
and slightly but significantly improved for the 25-cm narrow-path walk, 7-m usual
pace, 7-m obstacle normal light, 7-m holding a package, and 7-m talking while
walking tests. Test-retest reliability was in general very high, with 11 of 14
(79%) of the intraclass correlation coefficient values >0.80 and all except one
(7-m holding a package) >0.75. CONCLUSION: The walking tests included in the
Walking InCHIANTI Toolkit show very good medium-term reproducibility and modest
learning effect. Administering components of the Walking InCHIANTI Toolkit may
help in the understanding of the effect of challenges encountered in daily life
on walking performance.
PMID- 17033596
TI - Thoracic endovascular repair--this is just the beginning.
PMID- 17033597
TI - Interventional strategies for treatment of aortic dissection.
AB - Endovascular treatment of chronic aneurysmatic diseases of the thoracic aorta has
demonstrated encouraging peri-interventional mortality and morbidity and is
accepted as a preferred strategy. The emerging of endovascular strategies for
acute thoracic aortic dissection is an even more exciting new territory for
nonsurgical interventions considering the sobering results of open surgery.
Although it is apparent that patients at high risk for open surgery will benefit
from endovascular strategies, the exact role of stent-graft placement remains to
be defined at present as the community awaits solid long-term data and as devices
and techniques continue to improve. While some indications and scenarios such as
acute type B dissection with associated malperfusion syndrome or imminent aortic
rupture have shown to benefit from stent-graft treatment, others are less
settled. The current paper discusses both the established and emerging
indications, as well as all technical aspects of this fascinating new therapeutic
alternative. Moreover, the currently available data from small studies and
registries are commented and analysed. Based on the available information the
cardiovascular community is in the early phase of integrating a new rapidly
evolving interventional concept into the care of patients with type B aortic
dissection that so far lacked a reasonable therapeutic option other than blood
pressure lowering medication. With the use and interpretation of current
information the reader will understand the potential of interventional stent
graft induced thoracic aortic repair in type B aortic dissection.
PMID- 17033598
TI - Novel technique: staged hybrid surgical and endovascular treatment of acute Type
A aortic dissections with aortic arch involvement.
AB - AIM: The standard approach for treating acute Type A aortic dissections (TAD) is
replacement of the ascending aorta utilizing hypothermic circulatory arrest
(HCA), which is associated with significant morbidity and frequently leaves a
residual aortic arch dissection. We describe a staged surgical and endovascular
technique of ascending aorta replacement and simultaneous aorto-innominate artery
bypass without HCA, followed 4 weeks later by carotid-carotid bypass and
endovascular exclusion of the remaining arch dissection with a thoracic
endograft. METHODS: From December 2004 to December 2005, 5 consecutive patients
(mean age 58 +/- 6.9 years) with TADs underwent the staged procedure. All
patients underwent replacement of the ascending aorta and aorto-innominate
bypass. Two patients subsequently underwent the second endovascular stage. In one
patient the aortic false lumen completely thrombosed following the first surgical
stage and two patients are currently awaiting the endovascular stage. RESULTS:
There were no major adverse events (death, cerebrovascular accident or
paraplegia) following the first surgical stage. One patient suffered a transient
minor stroke. The 2 patients who underwent the second endovascular stage showed
no immediate adverse events. Postoperative CT scans have demonstrated that the
false channel was excluded from the aortic arch down to the distal end of the
endograft in the descending aorta in each case, but became patent further
downstream. CONCLUSIONS: This procedure appears safe and feasible. It may allow
for a more definitive treatment of TADs than the standard surgical approach. It
can be adapted by low volume centers, surgeons untrained in aortic arch repair,
and in high risk patients.
PMID- 17033599
TI - Remodeling of the thoracic aorta after stent grafting of type B dissection: a
Swedish multicenter study.
AB - AIM: Endovascular repair of complicated type B dissections has evolved as a
promising alternative to open repair. Previous studies have indicated that
continued false lumen flow is a predictor of continued aortic dilatation and risk
of rupture during follow-up. This multicenter study was conducted to analyze the
postoperative changes of the false lumen after endografting of complicated type B
dissections. METHODS: All patients treated with endovascular stent grafts for
thoracic type B dissections at 5 major Vascular Centers in Sweden were identified
through local databases. Review of charts and all available pre- and
postoperative CT scans were performed to identify demographics, indications for
repair as well as postoperative changes of the aorta and false lumen. RESULTS: A
total of 129 patients treated for type B dissections between 1994 and December
2005 were identified. Median radiological follow-up was 14 months. Fourteen
patients died perioperatively leaving 115 patients available for analysis.
Seventy-four of these had CT imaging of sufficient quality for morphological
analysis. The vast majority of acute patients were treated for rupture or end
organ ischemia whereas most chronic patients were treated for asymptomatic
aneurysms. In 80% of patients, the false lumen thrombosed along the stent graft
but it remained perfused distal to the stent graft fixation in 50% of patients.
Only 5% of patients presented with aortic enlargement of the stent grafted area
when adequate proximal sealing was achieved. The distal, uncovered aorta
displayed expansion in 16% of patients. CONCLUSIONS: The stent grafted thoracic
aorta after type B dissection appears to be stabilized by covering the primary
entry site with a stent graft in the majority of both acute and chronic
dissections. The uncovered portion of the aorta distal to the stent graft,
however, remains at risk of continuous dilatation. Stent grafting for complicated
type B thoracic dissections seems to be a treatment option with reasonable
morbidity and mortality even though the incidence of severe complications is
still significant.
PMID- 17033600
TI - Hybrid aortic procedures for endoluminal arch replacement in thoracic aneurysms
and type B dissections.
AB - The aim of this study was to report our clinical experience with and review
current literature on endoluminal aortic hybrid techniques and to evaluate
outcome in high-risk patients treated for complex aortic arch lesions combining
conventional supra-aortic debranching bypasses with subsequent or staged thoracic
endovascular grafting. Of 172 patients treated with thoracic endografts for
different thoracic aortic pathologies within the last 8 years, the mid-aortic
arch was involved in 25, i.e. at least the left common carotid artery had to be
overstented and revascularized to provide a proper proximal landing zone. These
debranching bypasses were performed as a simultaneous or a staged procedure. All
patients were at high-risk and were excluded by cardiac surgeons as ineligible
for conventional arch repair. After partial (n=16) or complete (n=9) supra-aortic
transposition, 4 different commercially available endografts (80% TAG, WL Gore)
were implanted transfemorally or via iliac conduit. Deployment success was 100%
in 25 patients after simultaneous or staged supra-aortic transposition; in 32% an
emergency procedure was performed due to contained rupture; in 36% more than 1
endograft system was implanted (2 in 20%, 3 in 8% und 4 in 8%). The overall
perioperative thirty-day mortality was 5 of 25 (20%) due to interoperative
proximal bare stent perforation (n=1), transfusion related acute lung injury
(TRALI n=1), cardiac failure (n=1), embolic stroke (n=1) and pneumonia (n=1). The
mean follow-up was 21 months. All endoleaks type I (n=3) were corrected with
another endograft; the 2 endoleaks type II sealed spontaneously. The major
adverse events were: prolonged ventilation in 5 (20%), temporary renal
insufficiency with hemodialysis (n=2), bypass infection (n=1), without any
complications (n=9). No cases of paraplegia were recorded. Hybrid aortic arch
repair is technically challenging but feasible. This novel approach may be an
alternative to standard open procedures in high-risk patients and emergency
cases. However, the promising early results need to be confirmed by longer follow
up and larger series.
PMID- 17033602
TI - Laparoscopic assisted aortic surgery. A review.
AB - We give an overview of different laparoscopic assisted techniques to perform
aortic surgery. In a meta-analysis the paper describes the combined experience of
two vascular surgical centers who together have performed more than 524
laparoscopic assisted aortic procedures. Basically the following techniques can
be used to perform a laparoscopic assisted procedure: 1) transperitoneal approach
(the Alimi procedure); 2) hand assisted laparoscopy (the Ferrari technique); 3)
left retrocolic laparoscopic assisted; 4) combining laparoscopic assisted and
total laparoscopy techniques. In all cases a transperitoneal approach was chosen
to dissect the aorta. This was either accomplished directly or using a left
retrocolic access originally described by Dion as the apron technique. In some
cases a hand assist device was used, which permits the surgeon to introduce the
non dominant hand while maintaining the pneumoperitoneum. The mortality in
abdominal aortic aneurysm (AAA) patients in either center did not exceed 1.8%.
ICU stay, postoperative ileus and length of stay were significantly shorter
compared to patients with a full length incision. The Pisa group showed that
there is still a significant reduction of operating time as well as aortic cross
clamping time beyond the learning curve of the first 30 patients. The analysis of
the pooled data shows that even in AAA patients the laparoscopic assisted
procedure can be performed with operating times of less than 3 h and hospital
stays up to 4 days, which we only know from endovascular aneurysm exclusion. This
is the first publication of hand assisted laparoscopic endoaneurysm repair
involving a large number of patients. The operations can be performed with
expediency and safety. We can use these laparoscopic procedures to perform even
complex aortic operations including suprarenal aneurysms with revascularization
of the renal and visceral arteries. An outlook of future developments including
stapling technology is given.
PMID- 17033601
TI - Carotid angioplasty and stenting under protection. Techniques, results and
limitations.
AB - A carotid stenosis is responsible for about 30% of strokes occurring. Carotid
endarterectomy (CEA) is considered to be the gold standard treatment of a carotid
stenosis. Carotid angioplasty and stenting (CAS) is emerging as a new alternative
treatment for a carotid artery stenosis, but the risk of neurological
complications and brain embolism remains the major drawback to this procedure.
Therefore, in order to reduce the risks, we need: 1) good indications, good
patient and lesion selection; 2) correct techniques; 3) brain protection devices
(cerebral protection devices should be routinely used and are mandatory for any
procedure); 4) 3 types of protection devices are available, but filters are the
most commonly used (all protection devices have limitations and cannot prevent
from all embolic events; however, neurological complications can be reduced by
60%); 5) a good choice of the stent and correct implantation (all stents are not
equivalent and have different geometrical effects); 6) pharmacological adjuncts;
7) a good team. Recent studies have shown that CAS has superior short-term
outcomes than CEA in high surgical risk patients, but there are enough reported
data to conclude that CAS is also not inferior to CEA in low-risk patients. CAS
under protection is the standard of care and is maybe becoming the gold standard
treatment of a carotid stenosis at least in some subgroups of patients.
PMID- 17033603
TI - Shrinkage of abdominal aortic aneurysm after successful endovascular repair:
results from single center study.
AB - AIM: In the literature, the behavior of the aneurysm sac after endovascular
grafting has been the subject of significant speculation. It has been suggested
that shrinkage of the abdominal aortic aneurysm (AAA) is different for various
endografts. This study was undertaken to evaluate endograft-specific differences
in aneurysm sac shrinkage and to evaluate other factors that may influence AAA
shrinkage. METHODS: Forty patients with an AAA treated with endovascular grafts
with a complete 18 months follow-up and complete CT angiography (CTA) follow-up
were available for analysis. All patients with a persistent endoleak, endograft
migration or any other reason for intervention or conversion were excluded from
this analysis. Shrinkage was defined as a reduction in the AAA diameter of 5 mm
or more. Chi-squared tests were used to test whether shrinkage was different for
the kind of stent graft used (Gore Excluder vs Cook-Zenith), preexistent AAA
diameter (<65 mm vs =or>65 mm), and AAA status (ruptured vs non-ruptured) (two
sided; a= 0.05). RESULTS: At 18 months after treatment, shrinkage was observed in
14 patients (52%) of the 27 patients treated with a Gore Excluder endograft and
in 8 patients (62%) of the 13 patients treated with a Cook Zenith endograft
(P=0.74). In 31 patients with a diameter <65 mm, shrinkage was observed in 19
patients (61%) whereas of the 9 patients with a diameter =or>65 mm, shrinkage was
observed in 3 patients (33%) (P=0.253). Of the 34 patients with a non-ruptured
AAA, shrinkage was observed in 18 patients (53%) versus of the 6 patients with a
ruptured AAA shrinkage was observed in 4 patients (66%) (P=0.673). CONCLUSIONS:
From this study can be concluded that the influence of the endograft on shrinkage
of the AAA sac might be less prominent than suggested in the literature.
Furthermore, our study shows that other factors such as preexistent AAA diameter
may influence AAA shrinkage after endovascular repair.
PMID- 17033605
TI - Clinical outcome after composite grafting of calcified left anterior descending
arteries.
AB - AIM: The treatment of a severely calcified left anterior descending coronary
artery (LAD) remains a challenge in cardiac surgery. The objective of this
retrospective study was to assess the early clinical outcome obtained from LAD
reconstruction, which was performed using a combination of both, saphenous vein
and the left internal thoracic artery (LITA) as a composite graft, in order to
achieve complete revascularization. METHODS: Between January 1998 and December
2003, 71 patients, 13 female and 58 male, with a mean age of 67+/-9.12 years were
retrospectively analyzed. All patients suffered from a severe 3-vessel disease
with a diffusely calcified LAD. The design of the reconstruction consisted in a
long arteriotomy of the LAD grafted with a matched segment of the saphenous vein
using the plaque exclusion technique to avoid endarterectomy. The LITA was then
anastomosed to the saphenous vein in an end-to-end configuration. With this
design, the saphenous vein was used first as a ''patch'' reconstruction of the
LAD and second as an elongation for the LITA. The clinical outcome was assessed
by mailed questionnaires or by telephone interview with the responsible
cardiologist or general practitioner. RESULTS: The follow-up was 100%, comprising
a mean follow-up time of 17+/-11.8 months. Overall mortality was 7% (N=5/71).
Four cardiac deaths and 1 non cardiac-related death were registered. The in
hospital mortality was 2.8% (2/71); 2 cardiac-related deaths and one non cardiac
related death were observed after 30 days (4.2%). Postoperative myocardial
infarction without heart failure was seen in 4 patients (5.4%). In addition, an
episode of transitory cerebral ischemia was observed in 1 patient (1.4%). No
further postoperative complications occurred. At the time of evaluation, 67% of
the patients were in functional class CCS 0 and 33% in functional class CCS I to
II. CONCLUSIONS: Composite graft reconstruction without endarterectomy is an
alternative treatment option for severely calcified LADs with a good early
clinical outcome.
PMID- 17033604
TI - The role of N-acetylcysteine in lower extremity ischemia/reperfusions.
AB - AIM: To evaluate the efficacy of N-acetyl cysteine (NAC) in lower extremity
ischemia/reperfusion. METHODS: A total of 23 patients who underwent surgical
intervention due to acute femoral artery occlusion were assigned into 2 groups:
control group (group 1, n=12); and NAC group (group 2, n=11). Patients in NAC
group received NAC before reperfusion, and 8 and 16 h after reperfusion (3x300
mg), while patients in control group received only NaCl 0.9% (3x100 mL).
Catalase, malondialdehyde (MDA) and thiol concentrations were determined in
femoral vein samples collected at 6 different time points: before reperfusion
(t1), and 30 min (t2), 2 h (t3), 6 h (t4), 12 h (t5) and 24 h (t6) after
reperfusion. Alveolar-arterial oxygen gradient (A-aO2) was calculated in radial
artery blood samples simultaneously collected at the same time points. RESULTS:
No significant differences between the two groups with regard to age (control
group 61+/-13 and NAC group 64+/-11 years), gender (control group M/F: 7/5, NAC
6/5) and the average time from onset of symptoms (control group 9.6+/-3.5 h, and
NAC group 10.2+/-3.1 h) were present. Catalase enzyme activity increased with
reperfusion in both groups and there were no differences between the two groups.
MDA levels did not change significantly with reperfusion in NAC group, whereas
they were significantly higher in control group at t2 and t3 compared to NAC
group (P<0.05). Thiol concentrations decreased with reperfusion in control group,
and in NAC group increases that started with reperfusion returned back to
baseline levels after 24 hours. Although the A-aO2 gradient increased in both
groups with the beginning of reperfusion, the most prominent increase occurred in
control group (P<0.05). CONCLUSIONS: In control group, the significant increase
in MDA levels and A-aO2 gradient in reperfusion phase were considered a sign of
local and end organ injury. We did not observe these changes in NAC performed
group thus showing the efficacy of NAC.
PMID- 17033606
TI - Beating heart mitral valve replacement with retrograde coronary sinus perfusion
technique.
AB - AIM: The aim of this study was to assess the efficacy and applicability of on
pump beating heart mitral valve replacement with Sorin Bicarbon prosthesis using
retrograde coronary sinus perfusion. METHODS: The prospective study included 17
consecutive patients who underwent mitral valve replacement with Sorin Bicarbon
prosthesis using retrograde coronary sinus perfusion. The operative variables and
early outcome of this procedure are presented. RESULTS: Retrograde coronary sinus
perfusion and venting the heart from the aorta and from the pulmonary vein
provided good visualization of the operative field and performance of the
operations without any difficulty. Partial oxygen pressures of coronary sinus
perfusion blood and the returning blood from the coronary ostia were 299.7+/-30.7
and 37.6+/-6.2 mmHg respectively. Postoperative peak creatine kinase-MB and
troponin T values were 58+/-28.5 IU/L and 1.5+/-0.4 ng/mL, respectively. No
mortality or major complication was observed and all the patients were discharged
from the hospital in good condition. CONCLUSIONS: On-pump beating heart mitral
valve replacement with Sorin Bicarbon is a good surgical option, and it has the
advantage of maintaining physiologic condition of the heart throughout the
procedure.
PMID- 17033607
TI - ''BioGlue'' as a possible cause of acute blocked mechanical mitral valve leaflet.
AB - A young patient with aortic and mitral valve infective endocarditis and advanced
destruction of the surrounding tissues underwent a complex reconstructive
surgery, including double valve replacement, reconstruction of aortic-mitral
continuity and ascending aorta. Intraoperative transesophageal echocardiography
revealed a blocked mitral leaflet, which was released by valve cleaning and
reorientation. The application of biological glue may be a key point for this
complication.
PMID- 17033608
TI - Perioperative optic neuropathy following off-pump coronary artery bypass
grafting.
AB - Visual loss from ischemic perioperative optic neuropathy (PON) rarely occurs
during the postoperative period of patients undergoing cardiac surgery. Since the
first description, PON has been associated with cardiopulmonary bypass (CPB),
being some CPB-related complications and epiphenomena considered the causes of
such terrible complication. In particular, the risk for micro-embolization during
aortic cannulation and clamping, the CPB-related inflammatory response, the
hemodilution and the hypothermia during CPB could be responsible of PON. However,
some cases of PON still remain idiopathic. We report here a very rare case of PON
following off-pump surgery in a patient with severe coronary disease and
multiorgan comorbidities. The case reported opens the debate on the potential
mechanisms underlying PON, other than cardiopulmonary bypass.
PMID- 17033609
TI - Aortic root replacement in cardiac dextroversion.
AB - Adult cardiac surgery in patients with malrotation of the heart is rare. A 60
year-old lady, with known cardiac dextroversion, presented with dyspnoea and pre
syncopal attacks. Echocardiographical and radiological investigation confirmed
the dextroversion, with clockwise rotation of the heart through its longitudinal
axis. This resulted in the right ventricular outflow tract and pulmonary artery
being wrapped anteriorly around the aorta, with posterior displacement of the
right atrium. The presence of a heavily calcified, bicuspid aortic valve and
dilated ascending aorta was also demonstrated. At surgery, venous cannulation was
established by rotating the heart anticlockwise and access to the aortic valve
gained with a more superior oblique aortotomy. In the presence of a dilated
ascending aorta with a calcified, bicuspid aortic valve, the aortic root was
replaced with a valved conduit. To the authors' knowledge, this is the first
report of an aortic root replacement in a patient with cardiac dextroversion.
PMID- 17033610
TI - The use of cardio-pulmonary double stage venous cannula as right inflow cannula
for bi-ventricular assist device.
PMID- 17033611
TI - 5-year prospective results of trimodality treatment for malignant pleural
mesothelioma.
AB - AIM: Even though followed by a prolonged survival in highly selected patients,
the promising results of Sugarbaker's trimodality treatment for malignant pleural
mesothelioma (MPM) are debated and not yet uniformly replicated. The purpose of
this study is to evaluate prospectively the reproducibility of the trimodality
treatment results in a patient population with mesothelioma staged by the IMIG
classification. METHODS: Fifty-four patients with MPM have been judged candidable
to extended pleuropneumonectomy (EPP), to be followed by chemotherapy
(paclitaxel+carboplatin) and radiotherapy (50 Gy). RESULTS: At thoracotomy, 44 of
the 54 surgical candidates (81%) underwent EPP; 73% of the operated patients
completed the entire adjuvant chemo-radiotherapy with no major toxicity. The 30
day or in-hospital operative mortality rate was 4.5% (2 deaths), the major
morbidity 36%, and the overall complication rate 50%. At 5 years the projected
survival of the 42 surgical survivors submitted to EPP is 19%; median survival is
20 months. The restricted group of patients with epithelial, N0-1, completely
resected MPM (microscopic negative margins) exhibits a projected 50% 5-year
survival. Clinical understaging has shown up to be noticeable both at the
thoracotomy exploration and pathology examination. Most of the disease
recurrences are loco-regional and the current insufficiency of intraoperative or
postsurgical radicality needs improvement, along with earlier diagnosis, more
accurate staging, and preoperative induction for the multimodality treatment of
pleural mesothelioma to become an established curative option. CONCLUSIONS: This
series confirms the reproducibility of the trimodality treatment for MPM,which is
associated with prolonged survival for early-stage tumors at the cost of a not
prohibitive treatment-related mortality rate.
PMID- 17033612
TI - Predictors of long-term survival with pulmonary metastasectomy for osteosarcomas
and soft tissue sarcomas.
AB - AIM: The control of pulmonary metastases is important for long-term survival of
the patients with osteosarcomas and soft tissue sarcomas. METHODS: To evaluate
the efficacy of aggressive pulmonary metastasectomy for those patients, we
reviewed 105 cases (44 osteosarcomas, and 61 soft tissue sarcomas) treated in our
hospital. RESULTS: The number of metastases was only the significant risk factor
for the curability of the metastasectomy (logistic regression analysis,
P=0.0274). The 5-year and 10-year survival rate were 43.6% and 32%. The
curability was only independent prognostic factor on multivariate analysis
(P=0.0008). CONCLUSIONS: Early detection of pulmonary metastasis, multimodal
perioperative treatment, and design for minimizing the volume of resected lung
tissues will enable complete and repeat resections for the achievement of long
term survival.
PMID- 17033613
TI - Pulmonary vein thrombosis after lower lobectomy of the left lung.
AB - Pulmonary vein thrombosis is a known complication after lung transplantation but
has rarely been reported after lobectomy or bilobectomy. We report the case of a
left upper pulmonary vein thrombosis following an uneventful left lower lobectomy
for bronchial carcinoma. Postoperative arterial blood gas values and chest
radiographs were normal. On postoperative day 5, the patient became progressively
dyspneic, developed hemoptysis and showed total opacification of the left lung
without mediastinal shift on chest radiography. The patient remained dyspneic
despite intravenous antibiotic therapy for suspected pneumonia and absence of
obstruction at bronchoscopy. Diagnosis of left upper pulmonary vein thrombosis
was finally made by contrast-enhanced multislice computed tomography followed by
pulmonary angiography. Further clinical deterioration under conservative
treatment forced us to remove the remnant left upper lobe that already showed
gangrenous alterations. Pulmonary vein thrombosis following lobectomy or
bilobectomy is very rare. Only 7 cases have been reported in the literature so
far. Conservative treatment with antibiotics and anticoagulants may be successful
but in case of clinical deterioration the affected lobe has to be resected. The
mechanism of thrombosis remains unclear although intraoperative torsion and
injury of vessels seem to be most likely since pulmonary vein thrombosis occurred
in the operated hemithorax only.
PMID- 17033614
TI - Pharmacogenetics and ethical considerations: why care?
PMID- 17033615
TI - Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent
functional genomics approach.
AB - We describe a comprehensive translational approach for identifying candidate
genes for alcoholism. The approach relies on the cross-matching of animal model
brain gene expression data with human genetic linkage data, as well as human
tissue data and biological roles data, an approach termed convergent functional
genomics. An analysis of three animal model paradigms, based on inbred alcohol
preferring (iP) and alcohol-non-preferring (iNP) rats, and their response to
treatments with alcohol, was used. A comprehensive analysis of microarray gene
expression data from five key brain regions (frontal cortex, amygdala, caudate
putamen, nucleus accumbens and hippocampus) was carried out. The Bayesian-like
integration of multiple independent lines of evidence, each by itself lacking
sufficient discriminatory power, led to the identification of high probability
candidate genes, pathways and mechanisms for alcoholism. These data reveal that
alcohol has pleiotropic effects on multiple systems, which may explain the
diverse neuropsychiatric and medical pathology in alcoholism. Some of the
pathways identified suggest avenues for pharmacotherapy of alcoholism with
existing agents, such as angiotensin-converting enzyme (ACE) inhibitors.
Experiments we carried out in alcohol-preferring rats with an ACE inhibitor show
a marked modulation of alcohol intake. Other pathways are new potential targets
for drug development. The emergent overall picture is that physical and
physiological robustness may permit alcohol-preferring individuals to withstand
the aversive effects of alcohol. In conjunction with a higher reactivity to its
rewarding effects, they may able to ingest enough of this nonspecific drug for a
strong hedonic and addictive effect to occur.
PMID- 17033616
TI - Evaluation of ideal irrigation fluid in 'Greenlight' photoselective vapourization
of the prostate.
AB - Although many anecdotal opinions are available that water gives a better visual
quality, no studies have analysed the differences in the visual quality of the
operative field with the use of either saline or sterile water. As part of a
prospective audit we wished to assess the effect of differing irrigant fluids on
intraoperative visibility during Greenlight photoselective vapourization of
prostate (PVP). Twenty-nine consecutive patients with prostates less than 100
cm(3) who underwent PVP were studied. The irrigation fluid used was randomly
connected on a bag-by-bag basis, with the surgeon blinded to the bag's contents.
Towards the end of each bag the surgeon gave a score to the quality of vision.
All surgeons were familiarized with the vision scoring system in advance. The
scores were analysed in two ways. The mean scores for water and saline were
compared. In addition, a mean score for each fluid in each patient where both
fluids were used (n=24) was separately calculated and the means for each fluid
compared. One hundred and twenty-four bags of fluid in 29 operative cases were
analysed. The mean overall vision scores were 3.94% for saline and 4.01% for
water (P=0.62). The paired data were analysed using the Student's t-test and
there was no statistically significant difference (P=0.34). We showed no
significant difference in visual quality between water and saline during PVP.
Although fluid absorption is almost unknown with PVP, there seems to be no
justification for using water irrigation if saline is available, particularly
with a theoretical risk of absorption.
PMID- 17033617
TI - Diabetes and the risk of prostate cancer: the role of diabetes treatment and
complications.
AB - Epidemiologic evidence suggests diabetic men have a slightly lower prostate
cancer risk than non-diabetic men. We examined this association in a prospective
cohort study of 35 239 men, 50-76 years old, in Washington State who completed a
baseline questionnaire between 2000 and 2002. Incident prostate cancers as of 31
December 2004 were identified through the SEER registry. Diabetic men had a
slightly lower risk of prostate cancer than non-diabetic men (hazard ratio (HR)
0.83, 95% confidence interval (CI) 0.64-1.07). Insulin users overall and insulin
users with diabetic complications had decreased risks, compared to non-diabetic
men (HR 0.49, 95% CI 0.26-0.92) and (HR 0.36, 95% CI 0.15-0.87), respectively.
Oral medication use for diabetes was not associated with prostate cancer. Insulin
is likely a marker of severity of diabetes. Future studies of this association
should consider diabetes type, treatment, severity, complications and biomarkers.
PMID- 17033618
TI - Salt wasting, hypotension, polydipsia, and hyponatremia and the level of spinal
cord injury.
AB - STUDY DESIGN: Case control. OBJECTIVE: To test the reported correlation of
hypotension, polydipsia, and hyponatremia with higher levels of spinal cord
injury (SCI). SETTING: A Veterans Administration Hospital, USA. METHODS: The
records of men who were paralyzed owing to trauma at any spinal cord level with
motor complete lesions (ASIA A or B) and who received an annual physical and
laboratory examination were reviewed for age, duration of paralysis, level of
paralysis, blood pressure (BP), serum sodium, and 24 h urinary volume,
creatinine, and sodium. Creatinine clearance and fractional excretion of sodium
(FcNa) were calculated. Spearman rank-order correlations (r (s)) were carried
out. RESULTS: Patients were aged 25 to 88 years, median 56 years, paralyzed 2-61
years, median 26 years, with levels of paralysis ranging from C2 to L4, median
T4, n=111. From lower to higher levels of paralysis FcNa increased (0.4-7.3%),
mean BP diminished (132-66 mmHg), urine volume increased (600-5400 ml), and serum
sodium was reduced (148-129 mEq/l) - r (s)=0.29, 0.49, -0.22, and 0.23,
respectively. Increasing 24 h urinary volumes correlated with lower serum sodium
concentrations but higher creatinine clearance, r (s)=-0.28, 0.24. Increasing 24
h urinary sodium improved creatinine clearance, r (s)=0.37. P-values ranged from
<0.05 to <0.001. CONCLUSION: Higher levels of SCI correlate with reduced sodium
conservation, hypotension, polydipsia, and hyponatremia. Greater water intake
raises creatinine clearance but lowers serum sodium. Greater salt intake
increases creatinine clearance.
PMID- 17033619
TI - Spinal cord injury influences psychogenic as well as physical components of
female sexual ability.
AB - STUDY DESIGN: Secure, web-based survey. OBJECTIVES: Elicit specific information
about sexual function from women with spinal cord injuries (SCI). SETTING: World
wide web. METHODS: Individuals 18 years or older living with SCI obtained a pass
code to enter a secure website and then answered survey questions. RESULTS:
Bladder and/or bowel incontinence during sexual activity and/or sexual
intercourse were significant concerns and prevented some women from seeking
sexual activity. Autonomic dysreflexia (AD) during sexual activity was
interpreted negatively by many and was found to interfere with sexual activity.
Most subjects reported difficulty becoming psychologically aroused as well as
physically aroused, which were both correlated with feeling that their SCI had
altered their sexual sense of self. An inverse relationship existed between
developing new areas of arousal above the level of lesion and not having
sensation or movement below the lesion. The most commonly reported sexual
stimulation leading to the best arousal involved stimulation of the head/neck and
torso areas. The majority of subjects reported having experienced intercourse
postinjury. Most participants reported difficulty with positioning during
foreplay and intercourse, vaginal lubrication, and spasticity during intercourse.
Almost half reported experiencing orgasm postinjury and this was positively
associated with the presence of genital sensation. CONCLUSION: SCI significantly
impairs psychological and physical aspects of female sexual arousal. In addition,
bladder and bowel incontinence as well as AD negatively impact sexual activity
and intercourse.
PMID- 17033620
TI - The impact of spinal cord injury on sexual function: concerns of the general
population.
AB - STUDY DESIGN: Secure, web-based survey. OBJECTIVES: Obtain information from the
spinal cord injured (SCI) population regarding sexual dysfunctions, with the aim
of developing new basic science and clinical research and eventual therapies
targeting these issues. SETTING: Worldwide web. METHODS: Individuals 18 years or
older living with SCI. Participants obtained a pass-code to enter a secure
website and answered survey questions. A total of 286 subjects completed the
survey. RESULTS: The majority of participants stated that their SCI altered their
sexual sense of self and that improving their sexual function would improve their
quality of life (QoL). The primary reason for pursuing sexual activity was for
intimacy need, not fertility. Bladder and bowel concerns during sexual activity
were not strong enough to deter the majority of the population from engaging in
sexual activity. However, in the subset of individuals concerned about bladder
and/or bowel incontinence during sexual activity, this was a highly significant
issue. In addition, the occurrence of autonomic dysreflexia (AD) during typical
bladder or bowel care was a significant variable predicting the occurrence and
distress of AD during sexual activity. CONCLUSION: Sexual function and its
resultant impact on QoL is a major issue to an overwhelming majority of people
living with SCI. This certainly constitutes the need for expanding research in
multiple aspects to develop future therapeutic interventions for sexual health
and SCI.
PMID- 17033621
TI - Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes
in mineral metabolism.
AB - The osteocyte, a terminally differentiated cell comprising 90%-95% of all bone
cells, may have multiple functions, including acting as a mechanosensor in bone
(re)modeling. Dentin matrix protein 1 (encoded by DMP1) is highly expressed in
osteocytes and, when deleted in mice, results in a hypomineralized bone
phenotype. We investigated the potential for this gene not only to direct
skeletal mineralization but also to regulate phosphate (P(i)) homeostasis. Both
Dmp1-null mice and individuals with a newly identified disorder, autosomal
recessive hypophosphatemic rickets, manifest rickets and osteomalacia with
isolated renal phosphate-wasting associated with elevated fibroblast growth
factor 23 (FGF23) levels and normocalciuria. Mutational analyses showed that
autosomal recessive hypophosphatemic rickets family carried a mutation affecting
the DMP1 start codon, and a second family carried a 7-bp deletion disrupting the
highly conserved DMP1 C terminus. Mechanistic studies using Dmp1-null mice
demonstrated that absence of DMP1 results in defective osteocyte maturation and
increased FGF23 expression, leading to pathological changes in bone
mineralization. Our findings suggest a bone-renal axis that is central to guiding
proper mineral metabolism.
PMID- 17033622
TI - Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast
cancer susceptibility alleles.
AB - We identified constitutional truncating mutations of the BRCA1-interacting
helicase BRIP1 in 9/1,212 individuals with breast cancer from BRCA1/BRCA2
mutation-negative families but in only 2/2,081 controls (P = 0.0030), and we
estimate that BRIP1 mutations confer a relative risk of breast cancer of 2.0 (95%
confidence interval = 1.2-3.2, P = 0.012). Biallelic BRIP1 mutations were
recently shown to cause Fanconi anemia complementation group J. Thus,
inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause
Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer
in monoallelic carriers.
PMID- 17033623
TI - Nuclear organization of active and inactive chromatin domains uncovered by
chromosome conformation capture-on-chip (4C).
AB - The spatial organization of DNA in the cell nucleus is an emerging key
contributor to genomic function. We developed 4C technology (chromosome
conformation capture (3C)-on-chip), which allows for an unbiased genome-wide
search for DNA loci that contact a given locus in the nuclear space. We
demonstrate here that active and inactive genes are engaged in many long-range
intrachromosomal interactions and can also form interchromosomal contacts. The
active beta-globin locus in fetal liver preferentially contacts transcribed, but
not necessarily tissue-specific, loci elsewhere on chromosome 7, whereas the
inactive locus in fetal brain contacts different transcriptionally silent loci. A
housekeeping gene in a gene-dense region on chromosome 8 forms long-range
contacts predominantly with other active gene clusters, both in cis and in trans,
and many of these intra- and interchromosomal interactions are conserved between
the tissues analyzed. Our data demonstrate that chromosomes fold into areas of
active chromatin and areas of inactive chromatin and establish 4C technology as a
powerful tool to study nuclear architecture.
PMID- 17033624
TI - Circular chromosome conformation capture (4C) uncovers extensive networks of
epigenetically regulated intra- and interchromosomal interactions.
AB - Accumulating evidence converges on the possibility that chromosomes interact with
each other to regulate transcription in trans. To systematically explore the
epigenetic dimension of such interactions, we devised a strategy termed circular
chromosome conformation capture (4C). This approach involves a circularization
step that enables high-throughput screening of physical interactions between
chromosomes without a preconceived idea of the interacting partners. Here we
identify 114 unique sequences from all autosomes, several of which interact
primarily with the maternally inherited H19 imprinting control region. Imprinted
domains were strongly overrepresented in the library of 4C sequences, further
highlighting the epigenetic nature of these interactions. Moreover, we found that
the direct interaction between differentially methylated regions was linked to
epigenetic regulation of transcription in trans. Finally, the patterns of
interactions specific to the maternal H19 imprinting control region underwent
reprogramming during in vitro maturation of embryonic stem cells. These
observations shed new light on development, cancer epigenetics and the evolution
of imprinting.
PMID- 17033625
TI - DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix
protein in the regulation of phosphate homeostasis.
AB - Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an
autosomal recessive form (designated ARHP) to chromosome 4q21 and identified
homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non
collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact
plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of
four affected individuals, providing a possible explanation for the phosphaturia
and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may
regulate FGF23 expression.
PMID- 17033626
TI - Speciation genetics: evolving approaches.
AB - Much progress has been made in the past two decades in understanding Darwin's
mystery of the origins of species. Applying genomic techniques to the analysis of
laboratory crosses and natural populations has helped to determine the genetic
basis of barriers to gene flow which create new species. Although new
methodologies have not changed the prevailing hypotheses about how species form,
they have accelerated the pace of data collection. By facilitating the
compilation of case studies, advances in genetic techniques will help to provide
answers to the next generation of questions concerning the relative frequency and
importance of different processes that cause speciation.
PMID- 17033627
TI - The genetic dissection of essential hypertension.
AB - QTL mapping in humans and rats has identified hundreds of blood-pressure-related
phenotypes and genomic regions; the next daunting task is gene identification and
validation. The development of novel rat model systems that mimic many elements
of the human disease, coupled with advances in the genomic and informatic
infrastructure for rats, promise to revolutionize the hunt for genes that
determine susceptibility to hypertension. Furthermore, methods are evolving that
should enable the identification of candidate genes in human populations.
Together with the computational reconstruction of regulatory networks, these
methods provide opportunities to significantly advance our understanding of the
underlying aetiology of hypertension.
PMID- 17033628
TI - Brain morphological changes associated with exposure to HSV1 in first-episode
schizophrenia.
AB - Infectious agents have been proposed as one of the risk factors for
schizophrenia. However, the data on the association of infectious agents with in
vivo brain changes are scant. We evaluated the association of serological
evidence of exposure to herpes simplex virus 1 (HSV1) with in vivo brain
structural variations among first-episode antipsychotic-naive
schizophrenia/schizoaffective disorder patients and control subjects. We assayed
HSV1 immunoglobulin G (IgG) antibody in serum samples from 30 patients and 44
healthy subjects and obtained structural magnetic resonance imaging scans from
the same individuals. There were proportionately more patients with elevated HSV1
antibody ratios than healthy comparison subjects (chi2=3.98, 1 df, P=0.046) and
patients had significantly higher HSV1 IgG antibody ratios compared with healthy
subjects. Using optimized voxel-based morphometry, we examined diagnosis by HSV1
serological status interaction followed by within- and between-group comparison
across the serological status. We observed a diagnosis by HSV1 serological status
interaction and a significant main effect of HSV1 serological status in the
prefrontal gray matter. Patients exposed to HSV1 had decreased gray matter in
Brodmann area 9 (dorsolateral prefrontal cortex) and 32 (anterior cingulate
cortex) compared with patients without serological evidence of exposure to HSV1.
HSV1-associated differences in brain structure were not detected among healthy
subjects. These findings suggest that HSV1 exposure in schizophrenia is
associated with specific regional gray matter differences that may not be
attributable to medications, illness chronicity or comorbid substance use. This
study provides suggestive evidence for a link between HSV1 exposure and some of
the cerebral morphological changes often reported in schizophrenia.
PMID- 17033629
TI - Decreased circulating CD34+ stem cells in early Alzheimer's disease: Evidence for
a deficient hematopoietic brain support?
AB - Hematopoietic stem cells contribute to mammalian brain tissue regeneration by
transdifferentiation processes. We found decreased counts of circulating CD34+
cells in early Alzheimer's dementia (AD; P = 0.01), which significantly
correlated with age (r = -0.661; P = 0.001), cerebrospinal fluid beta-amyloid
(Abeta)1-42 (r = -0.467; P = 0.025) and most pronounced the Abeta42/40 ratio (r =
-0.688; P = 0.005). Our data suggest a deficient regenerative hematopoietic
support for the central nervous system in early AD.
PMID- 17033630
TI - Serotonin transporter gene variation impacts innate fear processing: Acoustic
startle response and emotional startle.
AB - Anxiety-related behaviors are closely linked to neural circuits relaying fear
specific information to the amygdala. Many of these circuits, like those
underlying processing of innate fear, are remarkably well understood. Recent
imaging studies have contributed to this knowledge by discriminating more
detailed corticoamygdalar associations mediating processing fear and anxiety.
However, little is known about the underlying molecular mechanisms. We used the
acoustic startle paradigm to investigate the impact of molecular genetic
variation of serotonergic function on the acoustic startle response and its fear
potentiation. Startle magnitudes to noise bursts as measured with the eye blink
response were recorded in 66 healthy volunteers under four conditions: presenting
unpleasant and pleasant affective pictures as well as neutral pictures, and
presenting the startle stimulus without additional stimuli as a baseline.
Subjects were genotyped for functional polymorphism in the transcriptional
control region of the serotonin transporter gene (5-hydroxytryptamine transporter
gene-linked region: 5-HTTLPR). Analyses of variance revealed a significant effect
of 5-HTTLPR on overall startle responses across conditions. Carriers of the short
(s) allele exhibited stronger startle responses than l/l homozygotes. However, we
could not confirm our hypothesis of enhanced fear potentiation of the startle in
s allele carriers. In conclusion, the results provide first evidence that the
startle response is sensitive to genetic variation in the serotonin pathway.
Despite some issues remaining to be resolved, the startle paradigm may provide a
valuable endophenotype of fear processing and underlying serotonergic influences.
PMID- 17033631
TI - Improvement of cognitive functions in chronic schizophrenic patients by
recombinant human erythropoietin.
AB - Schizophrenia is increasingly recognized as a neurodevelopmental disease with an
additional degenerative component, comprising cognitive decline and loss of
cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on
strategy, recombinant human erythropoietin (rhEPO) in addition to stable
antipsychotic medication, may be able to improve cognitive function even in
chronic schizophrenic patients. Therefore, we designed a double-blind, placebo
controlled, randomized, multicenter, proof-of-principle (phase II) study. This
study had a total duration of 2 years and an individual duration of 12 weeks with
an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with
defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for
the Assessment of Neuropsychological Status (RBANS)), stable medication and
disease state, were treated for 3 months with a weekly short (15 min) intravenous
infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was
schizophrenia-relevant cognitive function at week 12. The neuropsychological test
set (RBANS subtests delayed memory, language-semantic fluency, attention and
Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2
days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both
placebo and rhEPO patients improved in all evaluated categories. Patients
receiving rhEPO showed a significant improvement over placebo patients in
schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no
effects on psychopathology or social functioning. Also, a significant decline in
serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that
rhEPO is the first compound to exert a selective and lasting beneficial effect on
cognition should encourage new treatment strategies for schizophrenia.
PMID- 17033632
TI - Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes
for diagnosis and brain developmental trajectories.
AB - Childhood-onset schizophrenia (COS), defined as onset of psychosis by the age of
12, is a rare and malignant form of the illness, which may have more salient
genetic influence. Since the initial report of association between neuregulin 1
(NRG1) and schizophrenia in 2002, numerous independent replications have been
reported. In the current study, we genotyped 56 markers (54 single-nucleotide
polymorphisms (SNPs) and two microsatellites) spanning the NRG1 locus on 78 COS
patients and their parents. We used family-based association analysis for both
diagnostic (extended transmission disequilibrium test) and quantitative
phenotypes (quantitative transmission disequilibrium test) and mixed-model
regression. Most subjects had prospective anatomic brain magnetic resonance
imaging (MRI) scans at 2-year intervals. Further, we genotyped a sample of 165
healthy controls in the MRI study to examine genetic risk effects on normal brain
development. Individual markers showed overtransmission of alleles to affecteds
(P=0.009-0.05). Further, several novel four-marker haplotypes demonstrated
significant transmission distortion. There was no evidence of epistasis with SNPs
in erbB4. The risk allele (0) at 420M9-1395 was associated with poorer premorbid
social functioning. Further, possession of the risk allele was associated with
different trajectories of change in lobar volumes. In the COS group, risk allele
carriers had greater total gray and white matter volume in childhood and a
steeper rate of subsequent decline in volume into adolescence. By contrast, in
healthy children, possession of the risk allele was associated with different
trajectories in gray matter only and was confined to frontotemporal regions,
reflecting epistatic or other illness-specific effects mediating NRG1 influence
on brain development in COS. This replication further documents the role of NRG1
in the abnormal brain development in schizophrenia. This is the first
demonstration of a disease-specific pattern of gene action in schizophrenia.
PMID- 17033633
TI - Further evidence that the KIAA0319 gene confers susceptibility to developmental
dyslexia.
AB - The DYX2 locus on chromosome 6p22.2 is the most replicated region of linkage to
developmental dyslexia (DD). Two candidate genes within this region have recently
been implicated in the disorder: KIAA0319 and DCDC2. Variants within DCDC2 have
shown association with DD in a US and a German sample. However, when we genotyped
these specific variants in two large, independent UK samples, we obtained only
weak, inconsistent evidence for their involvement in DD. Having previously found
evidence that variation in the KIAA0319 gene confers susceptibility to DD, we
sought to refine this genetic association by genotyping 36 additional SNPs in the
gene. Nine SNPs, predominantly clustered around the first exon, showed the most
significant association with DD in one or both UK samples, including rs3212236 in
the 5' flanking region (P = 0.00003) and rs761100 in intron 1 (P = 0.0004). We
have thus refined the region of association with developmental dyslexia to
putative regulatory sequences around the first exon of the KIAA0319 gene,
supporting the presence of functional mutations that could affect gene
expression. Our data also suggests a possible interaction between KIAA0319 and
DCDC2, which requires further testing.
PMID- 17033634
TI - Plexin B3 is genetically associated with verbal performance and white matter
volume in human brain.
AB - The presence of genetic influences on cognitive performance and brain volume is
well established. However, specific genetic determinants of the variance of these
quantitative traits are not yet known. Plexins act as receptors for semaphorins
and are implicated in axon guidance, which is a key process in brain development.
We have previously shown that plexin B3 is a highly potent stimulator of neurite
outgrowth, which makes its gene PLXNB3 an intriguing candidate gene for traits
related to human brain development and cerebral connectivity. We identified
several polymorphisms in PLXNB3 predicting changes of amino acids (V598I, E1156D
and V1596E) conserved at the corresponding positions of the orthologs in mouse
and chimpanzee. PLXNB3 was genotyped in 303 healthy volunteers and 42 male
patients with schizophrenia. Cognitive performance was measured with the
vocabulary test (Wortschatztest (WST)), a method to estimate roughly general
intelligence (g). Brain morphology was characterized by magnetic resonance
imaging. Compared to subjects not carrying the modern, human-specific haplotype
A, carriers of A scored higher in vocabulary test (WST) irrespective of diagnosis
(P=0.0004). This effect could be observed in three independent groups (healthy
males: P=0.048; schizophrenic males: P=0.034 and healthy females: P=0.037).
Additionally, the haplotype A was associated with increased volume of brain white
matter that in turn correlated with performance in the vocabulary test. These
findings suggest that plexin B3 may influence cognitive performance, and the
development of white matter in vivo in a way similar to its known stimulating
effect on neurite outgrowth in vitro. These novel observations warrant further
replication in independent samples.
PMID- 17033636
TI - The genetics of autistic disorders and its clinical relevance: a review of the
literature.
AB - Twin and family studies in autistic disorders (AD) have elucidated a high
heritability of the narrow and broad phenotype of AD. In this review on the
genetics of AD, we will initially delineate the phenotype of AD and discuss
aspects of differential diagnosis, which are particularly relevant with regard to
the genetics of autism. Cytogenetic and molecular genetic studies will be
presented in detail, and the possibly involved aetiopathological pathways will be
described. Implications of the different genetic findings for genetic counselling
will be mentioned.
PMID- 17033635
TI - Region-specific transcriptional changes following the three antidepressant
treatments electro convulsive therapy, sleep deprivation and fluoxetine.
AB - The significant proportion of depressed patients that are resistant to
monoaminergic drug therapy and the slow onset of therapeutic effects of the
selective serotonin reuptake inhibitors (SSRIs)/serotonin/noradrenaline reuptake
inhibitors (SNRIs) are two major reasons for the sustained search for new
antidepressants. In an attempt to identify common underlying mechanisms for fast-
and slow-acting antidepressant modalities, we have examined the transcriptional
changes in seven different brain regions of the rat brain induced by three
clinically effective antidepressant treatments: electro convulsive therapy (ECT),
sleep deprivation (SD), and fluoxetine (FLX), the most commonly used slow-onset
antidepressant. Each of these antidepressant treatments was applied with the same
regimen known to have clinical efficacy: 2 days of ECT (four sessions per day),
24 h of SD, and 14 days of daily treatment of FLX, respectively. Transcriptional
changes were evaluated on RNA extracted from seven different brain regions using
the Affymetrix rat genome microarray 230 2.0. The gene chip data were validated
using in situ hybridization or autoradiography for selected genes. The major
findings of the study are: 1. The transcriptional changes induced by SD, ECT and
SSRI display a regionally specific distribution distinct to each treatment. 2.
The fast-onset, short-lived antidepressant treatments ECT and SD evoked
transcriptional changes primarily in the catecholaminergic system, whereas the
slow-onset antidepressant FLX treatment evoked transcriptional changes in the
serotonergic system. 3. ECT and SD affect in a similar manner the same brain
regions, primarily the locus coeruleus, whereas the effects of FLX were primarily
in the dorsal raphe and hypothalamus, suggesting that both different regions and
pathways account for fast onset but short lasting effects as compared to slow
onset but long-lasting effects. However, the similarity between effects of ECT
and SD is somewhat confounded by the fact that the two treatments appear to
regulate a number of transcripts in an opposite manner. 4. Multiple transcripts
(e.g. brain-derived neurotrophic factor (BDNF), serum/glucocorticoid-regulated
kinase (Sgk1)), whose level was reported to be affected by antidepressants or
behavioral manipulations, were also found to be regulated by the treatments used
in the present study. Several novel findings of transcriptional regulation upon
one, two or all three treatments were made, for the latter we highlight homer,
erg2, HSP27, the proto oncogene ret, sulfotransferase family 1A (Sult1a1),
glycerol 3-phosphate dehydrogenase (GPD3), the orphan receptor G protein-coupled
receptor 88 (GPR88) and a large number of expressed sequence tags (ESTs). 5.
Transcripts encoding proteins involved in synaptic plasticity in the hippocampus
were strongly affected by ECT and SD, but not by FLX. The novel transcripts,
concomitantly regulated by several antidepressant treatments, may represent novel
targets for fast onset, long-duration antidepressants.
PMID- 17033637
TI - Why silence is not an option.
AB - GM products will continue to be marginalized in Europe as long as industry
remains silent.
PMID- 17033638
TI - Partnering with a difference.
AB - This month marks the inaugural EuroBiO meeting, a new type of biotech partnering
event.
PMID- 17033639
TI - Parallel universes?
AB - An EU Commissioner has a meeting of minds with an antibiotech agitator.
PMID- 17033640
TI - Genentech raises stakes on PARP inhibitors.
PMID- 17033641
TI - Polyclonal antibodies step out of the shadows.
PMID- 17033642
TI - Poor enforcement could jeopardize China's drug innovation policy.
PMID- 17033643
TI - Brazil next biotech trailblazer in Latin America?
PMID- 17033645
TI - Profile. Michael Fernandez.
PMID- 17033646
TI - Biotech patenting upturn.
PMID- 17033647
TI - Turning plants into protein factories.
PMID- 17033648
TI - Reactions to Eprex's adverse reactions.
PMID- 17033649
TI - Potential impact and cost-effectiveness of Golden Rice.
PMID- 17033651
TI - The imitation game--a computational chemical approach to recognizing life.
PMID- 17033652
TI - Biotech buybacks--good or bad?
PMID- 17033654
TI - The emerging nanomedicine landscape.
PMID- 17033655
TI - Biotech patents and the inequitable conduct doctrine.
PMID- 17033656
TI - Recent patent applications in protein purification.
PMID- 17033657
TI - Putting proteins on the map.
PMID- 17033658
TI - Complementary therapies for inflammation.
PMID- 17033659
TI - Automated phosphorylation site mapping.
PMID- 17033660
TI - Deciphering bioplastic production.
PMID- 17033661
TI - Wastewater genomics.
PMID- 17033662
TI - A sugar switch for anti-inflammatory antibodies.
PMID- 17033664
TI - Deviant effects in molecular reaction pathways.
AB - In biological networks, any manifestations of behaviors substantially 'deviant'
from the predictions of continuous-deterministic classical chemical kinetics
(CCK) are typically ascribed to systems with complex dynamics and/or a small
number of molecules. Here we show that in certain cases such restrictions are not
obligatory for CCK to be largely incorrect. By systematically identifying
properties that may cause significant divergences between CCK and the more
accurate discrete-stochastic chemical master equation (CME) system descriptions,
we comprehensively characterize potential CCK failure patterns in biological
settings, including consequences of the assertion that CCK is closer to the
'mode' rather than the 'average' of stochastic reaction dynamics, as generally
perceived. We demonstrate that mechanisms underlying such nonclassical effects
can be very simple, are common in cellular networks and result in often
unintuitive system behaviors. This highlights the importance of deviant effects
in biotechnologically or biomedically relevant applications, and suggests some
approaches to diagnosing them in situ.
PMID- 17033665
TI - Post-translational modifications in the context of therapeutic proteins.
AB - The majority of protein-based biopharmaceuticals approved or in clinical trials
bear some form of post-translational modification (PTM), which can profoundly
affect protein properties relevant to their therapeutic application. Whereas
glycosylation represents the most common modification, additional PTMs, including
carboxylation, hydroxylation, sulfation and amidation, are characteristic of some
products. The relationship between structure and function is understood for many
PTMs but remains incomplete for others, particularly in the case of complex PTMs,
such as glycosylation. A better understanding of such structural-functional
relationships will facilitate the development of second-generation products
displaying a PTM profile engineered to optimize therapeutic usefulness.
PMID- 17033669
TI - The hardest hire: today's chief medical officer.
PMID- 17033678
TI - Indoor ultrafine particle exposures and home heating systems: a cross-sectional
survey of Canadian homes during the winter months.
AB - Exposure to airborne particulate matter has a negative effect on respiratory
health in both children and adults. Ultrafine particle (UFP) exposures are of
particular concern owing to their enhanced ability to cause oxidative stress and
inflammation in the lungs. In this investigation, our objective was to examine
the contribution of home heating systems (electric baseboard heaters, wood
stoves, forced-air oil/natural gas furnace) to indoor UFP exposures. We conducted
a cross-sectional survey in 36 homes in the cities of Montreal, Quebec, and
Pembroke, Ontario. Real-time measures of indoor UFP concentrations were collected
in each home for approximately 14 h, and an outdoor UFP measurement was collected
outside each home before indoor sampling. A home-characteristic questionnaire was
also administered, and air exchange rates were estimated using carbon dioxide as
a tracer gas. Average UFP exposures of 21,594 cm(-3) (95% confidence interval
(CI): 14,014, 29,174) and 6660 cm(-3) (95% CI: 4339, 8982) were observed for the
evening (1600-2400) and overnight (2400-0800) hours, respectively. In an
unadjusted comparison, overnight baseline UFP exposures were significantly
greater in homes with electric baseboard heaters as compared to homes using
forced-air oil or natural gas furnaces, and homes using wood stoves had
significantly greater overnight baseline UFP exposures than homes using forced
air natural gas furnaces. However, in multivariate models, electric oven use
(beta=12,253 cm(-3), 95% CI: 3524, 20,982), indoor relative humidity (beta=1136
cm(-3) %, 95% CI: 372, 1899), and indoor smoking (beta=18,192 cm(-3), 95% CI:
2073, 34,311) were the only significant determinants of mean indoor UFP exposure,
whereas air exchange rate (beta=4351 cm(-3) h(-1), 95% CI: 1507, 7195) and each
10,000 cm(-3) increase in outdoor UFPs (beta=811 cm(-3), 95% CI: 244,1377) were
the only significant determinants of overnight baseline UFP exposures. In
general, our findings suggest that home heating systems are not important
determinants of indoor UFP exposures.
PMID- 17033679
TI - On ecological fallacy, assessment errors stemming from misguided variable
selection, and the effect of aggregation on the outcome of epidemiological study.
AB - In social and environmental sciences, ecological fallacy is an incorrect
assumption about an individual based on aggregate data for a group. In the
present study, the validity of this assumption was tested using both individual
estimates of exposure to air pollution and aggregate data for 1,492
schoolchildren living in the in vicinity of a major coal-fired power station in
the Hadera region of Israel. In 1996 and 1999, the children underwent subsequent
pulmonary function tests (PFT), and their parents completed a detailed
questionnaire on their health status and housing conditions. The association
between children's PFT results and their exposure to air pollution was
investigated in two phases. During the first phase, PFT averages were compared
with average levels of air pollution detected in townships, and small census
areas in which the children reside. During the second phase, individual pollution
estimates were compared with individual PFT results, and pattern detection
techniques (Getis-Ord statistic) were used to investigate the spatial data
structure. While different levels of areal data aggregation changed the results
only marginally, the choice of indices measuring the children's PFT performance
had a significant influence on the outcome of the analysis. As argued,
differences between individual-level and group-level effects of exposure (i.e.,
ecological or cross-level bias) are not necessary outcomes of data aggregation,
and that seemingly unexpected results may often stem from a misguided selection
of variables chosen to measure health effects. The implications of the results of
the analysis for epidemiological studies are discussed, and recommendations for
public health policy are formulated.
PMID- 17033680
TI - Relative moldiness index as predictor of childhood respiratory illness.
AB - The results of a traditional visual mold inspection were compared to a mold
evaluation based on the Relative Moldiness Index (RMI). The RMI is calculated
from mold-specific quantitative PCR (MSQPCR) measurements of the concentration of
36 species of molds in floor dust samples. These two prospective mold evaluations
were used to classify the mold condition in 271 homes of infants. Later, the
development of respiratory illness was measured in the infants living in these
homes and the predictive value of each classification system was evaluated. The
binary classification of homes as either moldy or non-moldy by on-site visual
home inspection was not predictive of the development of respiratory illness
(wheeze and/or rhinitis) (P=0.27). Conversely, a method developed and validated
in this paper, using the RMI index fit to a logistic function, can be used to
predict the occurrence of illness in homes and allows stake-holders the choice
among various levels of risk.
PMID- 17033681
TI - Factors predicting organochlorine pesticide levels in pregnant Latina women
living in a United States agricultural area.
AB - Organochlorine (OC) pesticide use was restricted starting in the 1970s in
developed countries and the 1980s and 1990s in developing countries. Current
exposure to OC pesticides - dichlorodiphenyltrichloroethane (DDT), lindane (99%
pure gamma-hexachlorocyclohexane (gamma-HCH)), hexachlorobenzene (HCB) - occurs
on a limited basis. We measured para, para' (p,p')-DDE, p,p'-DDT, ortho, para'
(o,p')-DDT, HCB, beta (beta)-HCH (the most persistent isomer of technical-grade
HCH) and gamma-HCH in serum from 426 low-income pregnant Latina women living in
an agricultural community in California. Detection frequencies were 94% to 100%.
Median levels (ng/g lipid) of p,p'-DDE (1,052), p,p'-DDT (13), beta-HCH (37) and
HCB (65) were significantly higher than United States population levels.
Multivariate analyses of p,p'-DDE, p,p'-DDT, o,p'-DDT, beta-HCH and HCB indicate
that time spent living outside the United States and birthplace in an area of
Mexico with recent use of OC pesticides were significant predictors of exposure.
Time spent living in the United States was associated with increased serum levels
of p,p'-DDE and beta-HCH, but the increase for each year lived in the United
States was lower than for each year lived outside the United States. There was no
difference between the increase of HCB levels over time spent in or outside the
United States, suggesting current and thus preventable exposure routes. However,
we observed no associations between serum levels of any OC compound and current
intake of saturated fat or agricultural take-home exposure risk factors.
Lactation history and recent weight gain were negatively associated with serum
levels of some, but not all OC compounds studied. Smoking history was borderline
associated with elevated HCB levels. We observed no significant associations with
body mass index. Although the weight of evidence from this study indicates that
most exposure occurred before moving to the United States, the results for HCB
indicate the possibility of ongoing exposure in this country.
PMID- 17033682
TI - Macular degeneration: recent advances and therapeutic opportunities.
AB - The central retina mediates high acuity vision, and its progressive dysfunction
due to macular degeneration is the leading cause of visual disability among
adults in industrialized societies. Here, we summarize recent progress in
understanding the pathophysiology of macular degeneration and the implications of
this new knowledge for treatment and prevention. The past decade has witnessed
remarkable advances in this field, including the development of new, non-invasive
retinal imaging technologies, the development of animal models for macular
disease, and the isolation of many of the genes responsible for both early- and
late-onset macular diseases. These advances have set the stage for the
development of effective mechanism-based therapies.
PMID- 17033683
TI - Patterns of neural stem and progenitor cell division may underlie evolutionary
cortical expansion.
AB - The dramatic evolutionary expansion of the cerebral cortex of Homo sapiens
underlies our unique higher cortical functions, and therefore bears on the
ultimate issue of what makes us human. Recent insights into developmental events
during early proliferative stages of cortical development indicate how neural
stem and progenitor cells might interact to produce cortical expansion during
development, and could shed light on evolutionary changes in cortical structure.
PMID- 17033684
TI - Association analysis of the ACTN3 R577X polymorphism and complex quantitative
body composition and performance phenotypes in adolescent Greeks.
AB - The functional allele (577R) of ACTN3, which encodes human alpha-actinin-3, has
been reported to be associated with elite athletic status and with response to
resistance training, while the nonfunctional allele (577X) has been proposed as a
candidate metabolically thrifty allele. In a study of 992 adolescent Greeks, we
show that there is a significant association (P=0.003) between the ACTN3 R577X
polymorphism and 40 m sprint time in males that accounts for 2.3% of phenotypic
variance, with the 577R allele contributing to faster times in an additive
manner. The R577X polymorphism is not associated with other power phenotypes
related to 40 m sprint, nor with an endurance phenotype. Furthermore, the
polymorphism is not associated with obesity-related phenotypes in our population,
suggesting that the 577X allele is not a thrifty allele, and thus the persistence
of this null allele must be explained in other terms.
PMID- 17033685
TI - Repeat expansion in spinocerebellar ataxia type 17 alleles of the TATA-box
binding protein gene: an evolutionary approach.
AB - The variability and mutational changes of the CAG microsatellite in the TATA-box
binding protein gene (TBP) were studied. We sequenced the microsatellite of the
TBP gene of 25 unrelated individuals from northern Germany (10 SCA17 patients and
15 unaffected control individuals). In addition, the microsatellites were
sequenced from individuals of 10 northern German families with at least one
family member affected by SCA17. To study also the evolutionary history of this
CAG/CAA microsatellite in nonhuman primates, the homologous regions were analysed
from Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, P. abellii, Hylobates lar,
Nomascus leucogenys, Symphalangus syndactylus, Macaca mulatta, Papio hamadryas,
Colobus polykomos and Callithrix jacchus. Three major conclusions were drawn: (i)
Patterns of synonymous CAA interruptions in the microsatellite are characteristic
and likely to result from selection for stabilizing the repetitive region; (ii)
Interspecific comparisons indicate that SCA17 is likely to be a human trait. The
most common allele in humans (37 repeats) is close to the threshold value upon
which neurodegenerative changes can occur and may act as a repository for
expanded, pathogenic alleles; (iii) The cassette-like structure of five out of 17
expanded alleles can be attributed to unequal crossing over. This can explain the
rare and sporadic de novo generation of SCA17 alleles.
PMID- 17033686
TI - A two base pair deletion in the PQBP1 gene is associated with microphthalmia,
microcephaly, and mental retardation.
AB - X-linked mental retardation has been traditionally divided into syndromic (S
XLMR) and non-syndromic forms (NS-XLMR), although the borderlines between these
phenotypes begin to vanish and mutations in a single gene, for example PQBP1, can
cause S-XLMR as well as NS-XLMR. Here, we report two maternal cousins with an
apparently X-linked phenotype of mental retardation (MR), microphthalmia, choroid
coloboma, microcephaly, renal hypoplasia, and spastic paraplegia. By multipoint
linkage analysis with markers spanning the entire X-chromosome we mapped the
disease locus to a 28-Mb interval between Xp11.4 and Xq12, including the BCOR
gene. A missense mutation in BCOR was described in a family with Lenz
microphthalmia syndrome, a phenotype showing substantial overlapping features
with that described in the two cousins. However, no mutation in the BCOR gene was
found in both patients. Subsequent mutation analysis of PQBP1, located within the
delineated linkage interval in Xp11.23, revealed a 2-bp deletion, c.461_462delAG,
that cosegregated with the disease. Notably, the same mutation is associated with
the Hamel cerebropalatocardiac syndrome, another form of S-XLMR. Haplotype
analysis suggests a germline mosaicism of the 2-bp deletion in the maternal
grandmother of both affected individuals. In summary, our findings demonstrate
for the first time that mutations in PQBP1 are associated with an S-XLMR
phenotype including microphthalmia, thereby further extending the clinical
spectrum of phenotypes associated with PQBP1 mutations.
PMID- 17033687
TI - Positron emission tomography quantification of [11C]-(+)-PHNO binding in the
human brain.
AB - The kinetic modeling of [11C]-(+)-PHNO binding to the dopamine D2/3 receptors in
six human volunteers using positron emission tomography (PET) is described. [11C]
(+)-PHNO is the first agonist radioligand for the D2/3 in humans and as expected
showed high uptake in caudate, putamen, globus pallidus (GP) and ventral
striatum, and low uptake in cerebellum. A two-tissue compartment model (2CM) with
four parameters was necessary to adequately fit time-activity data in all
regions. Although a 2CM provided an excellent estimation of total distribution
volumes, which were highly correlated with those obtained with the invasive Logan
approach, it provided a poor identification of the k3/k4 ratios. Coupling K1/k2
between brain regions (Method C) or fixing K1/k2 to the value obtained in
cerebellum (Method D) enabled more stable estimates of k3/k4 as compared with an
unconstrained 2CM. The k3/k4 obtained with Method D ranged from 0.12+/-0.03 in
cerebellum to 3.93+/-0.77 in GP and were similar to those obtained when coupling
K1/k2. Binding potentials (BPs) obtained using the simplified reference tissue
model (BP(SRTM)) ranged from 2.08+/-0.34 in caudate to 3.55+/-0.78 in GP and were
highly correlated with k3/k4 estimates obtained with Method D (r=0.98). However,
BP(SRTM) were 11%+/-5% lower than values obtained with Method D. BPs derived
using the noninvasive Logan approach were slightly lower but not significantly
different than BP(SRTM). This study demonstrates that [11C]-(+)-PHNO can be used
for the quantitative measurement of D2/3 densities and should enable further
studies of potential D2/3 dysregulation in several important psychiatric and
neurologic illnesses.
PMID- 17033688
TI - Dynamics of changes in blood flow, volume, and oxygenation: implications for
dynamic functional magnetic resonance imaging calibration.
AB - Changes in cerebral blood flow (CBF), volume (CBV), and oxygenation (blood
oxygenation level dependent (BOLD)) during functional activation are important
for calculating changes in cerebral metabolic rate of oxygen consumption (CMRo2)
from calibrated functional MRI (fMRI). An important part of this process is the
CBF/CBV relationship, which is signified by a power-law parameter: gamma=ln
(1+DeltaCBV/CBV)/ln (1+DeltaCBF/CBF). Because of difficulty in measuring CBF and
CBV with MRI, the value of gamma is therefore assumed to be approximately 0.4
from a prior primate study under hypercapnia. For dynamic fMRI calibration, it is
important to know if the value of gamma varies after stimulation onset. We
measured transient relationships between DeltaCBF, DeltaCBV, and DeltaBOLD by
multimodal MRI with temporal resolution of 500 ms (at 7.0 T) from the rat
somatosensory cortex during forepaw stimulation, where the stimulus duration
ranged from 4 to 32 secs. Changes in CBF and BOLD were measured before the
administration of the contrast agent for CBV measurements in the same subjects.
We observed that the relationship between DeltaCBF and DeltaCBV varied
dynamically from stimulation onset for all stimulus durations. Typically after
stimulation onset and at the peak or plateau of the DeltaCBF, the value of gamma
ranged between 0.1 and 0.2. However, after stimulation offset, the value of gamma
increased to 0.4 primarily because of rapid and slow decays in DeltaCBF and
DeltaCBV, respectively. These results suggest caution in using dynamic
measurements of DeltaCBF and DeltaBOLD required for calculating DeltaCMRo2 for
functional stimulation, when either DeltaCBV has not been accurately measured or
a fixed value of gamma during hypercapnia perturbation is used.
PMID- 17033689
TI - Vascular response to hypoxic preconditioning in the immature brain.
AB - We hypothesized that hypoxic preconditioning (PC) modifies the microvasculature
in the immature brain and thereby affects the cerebral blood flow (CBF) during a
subsequent hypoxic-ischemic (HI) insult. On postnatal day 6 rats were exposed to
hypoxia (36 degrees C, 8.0% O2) or normoxia for 3 h. Unilateral HI (unilateral
carotid ligation and 8% hypoxia) was induced 24 h later. Cortical CBF was
measured with the 14C-iodoantipyrine technique (at the end of HI) or with laser
Doppler flowmetry (Perimed PF5001) before and during HI. At 0, 2, 8, and 24 h
cerebral cortex was sampled and analyzed with gene arrays (Affymetrix 230 2.0). L
nitroarginine or vehicle was administrated before hypoxic PC or 30 mins before HI
followed by CBF measurement (laser Doppler) during subsequent HI. Twenty-four
hours after PC animals were perfusion-fixed and brains immunolabeled for von
Willebrand factor and vascular density was determined by stereological
quantification. The decrease in CBF during HI was attenuated significantly in PC
versus control animals (P<0.01), as detected by both techniques. Several vascular
genes (Angpt2, Adm, Apln, Vegf, Flt1, Kdr, Pdgfra, Agtrap, Adora2a, Ednra,
serpine1, caveolin, Id1, Prrx1, Ero1l, Acvrl1, Egfl7, Nudt6, Angptl4, Anxa2, and
NOS3) were upregulated and a few (Csrp2, Adora2b) were downregulated after PC. A
significant increase in vascular density (P<0.05) was seen after PC. Nitric oxide
synthase inhibition did not affect CBF during HI after PC. In conclusion, hypoxic
PC upregulates vascular genes, increases vascular density and attenuates the
decrease of CBF during a subsequent HI, which could contribute to tolerance.
PMID- 17033690
TI - Myelin-associated inhibitory signaling and strategies to overcome inhibition.
AB - Numerous studies in the last two decades have resulted in significant progress in
our understanding of the role of inhibitors on axonal regeneration and conditions
that influence mature neurons to regrow in an inhibitory environment. These
studies have revealed putative therapeutic targets and strategies to interfere in
the inhibitory signaling cascade and promote axonal regeneration. Some agents
that were successful in animal models are now being tested in human patients. All
of these advances have raised hope of a cure for an injury that was once thought
to be 'an ailment for which nothing is done' (Quote from Edwin Smith surgical
papyrus, 1600BC).
PMID- 17033691
TI - Rho-kinase inhibition acutely augments blood flow in focal cerebral ischemia via
endothelial mechanisms.
AB - Rho-kinase is a serine threonine kinase that increases vasomotor tone via its
effects on both endothelium and smooth muscle. Rho-kinase inhibition reduces
cerebral infarct size in wild type, but not endothelial nitric oxide synthase
deficient (eNOS-/-) mice. The mechanism may be related to Rho-kinase activation
under hypoxic/ischemic conditions and impaired vasodilation because of
downregulation of eNOS activity. To further implicate Rho-kinase in impaired
vascular relaxation during hypoxia/ischemia, we exposed isolated vessels from rat
and mouse to 60 mins of hypoxia, and showed that hypoxia reversibly abolished
acetylcholine-induced eNOS-dependent relaxation, and that Rho-kinase inhibitor
hydroxyfasudil partially preserved this relaxation during hypoxia. We, therefore,
hypothesized that if hypoxia-induced Rho-kinase activation acutely impairs
vasodilation in ischemic cortex, in vivo, then Rho-kinase inhibitors would
acutely augment cerebral blood flow (CBF) as a mechanism by which they reduce
infarct size. To test this, we studied the acute cerebral hemodynamic effects of
Rho-kinase inhibitors in ischemic core and penumbra during distal middle cerebral
artery occlusion (dMCAO) in wild-type and eNOS-/- mice using laser speckle
flowmetry. When administered 60 mins before or immediately after dMCAO, Rho
kinase inhibitors hydroxyfasudil and Y-27632 reduced the area of severely
ischemic cortex. However, hydroxyfasudil did not reduce the area of CBF deficit
in eNOS-/- mice, suggesting that its effect on CBF within the ischemic cortex is
primarily endothelium-dependent, and not mediated by its direct vasodilator
effect on vascular smooth muscle. Our results suggest that Rho-kinase negatively
regulates eNOS activity in acutely ischemic brain, thereby worsening the CBF
deficit. Therefore, rapid nontranscriptional upregulation of eNOS activity by
small molecule inhibitors of Rho-kinase may be a viable therapeutic approach in
acute stroke.
PMID- 17033692
TI - Imaging of brain hypoxia in permanent and temporary middle cerebral artery
occlusion in the rat using 18F-fluoromisonidazole and positron emission
tomography: a pilot study.
AB - In acute stroke, the target of therapy is the severely hypoxic but salvageable
tissue. Previous human studies using 18F-fluoromisonidazole and positron emission
tomography (18F-FMISO PET) have shown high tracer retention indicative of tissue
hypoxia, which had normalized at repeat scan >48 h later. In the only validation
study of 18F-FMISO, using ex vivo autoradiography in thread middle cerebral
artery occluded (MCAo) rats, there was unexpected high uptake as late as 22 h
after reperfusion, raising questions about the use of 18F-FMISO as a hypoxia
tracer. Here we report a pilot study of 18F-FMISO PET in experimental stroke.
Spontaneous hypertensive rats were subjected to distal clip MCAo. Three-hour
dynamic PET was performed in 7 rats: 3 normals, 1 with permanent MCAo (two
sessions: 30 mins and 48 h after clip), and 3 with temporary MCAo (45 mins, n=1;
120 mins, n=2; scanning started 30 mins after clip removal). Experiments were
terminated by perfusion-fixation for standard histopathology. Late tracer
retention was assessed by both compartmental modelling and simple side-to-side
ratios. In the initial PET session of the permanent MCAo rat, striking trapping
of 18F-FMISO was observed in the affected cortex, which had normalized 48 h
later; histopathology revealed pannecrosis. In contrast, there was no
demonstrable tracer retention in either temporary MCAo models, and histopathology
showed ischemic changes only. These results document elevated 18F-FMISO uptake in
the stroke area only in the early phase of MCAo, but not after early reperfusion
nor when tissue necrosis has developed. These findings strongly support the
validity of 18F-FMISO as a marker of viable hypoxic tissue/penumbra after stroke.
PMID- 17033693
TI - Inflammation after intracerebral hemorrhage.
AB - Intracerebral hemorrhage (ICH) is a devastating clinical event without effective
therapies. Increasing evidence suggests that inflammatory mechanisms are involved
in the progression of ICH-induced brain injury. Inflammation is mediated by
cellular components, such as leukocytes and microglia, and molecular components,
including prostaglandins, chemokines, cytokines, extracellular proteases, and
reactive oxygen species. Better understanding of the role of the ICH-induced
inflammatory response and its potential for modulation might have profound
implications for patient treatment. In this review, a summary of the available
literature on the inflammatory responses after ICH is presented along with
discussion of some of the emerging opportunities for potential therapeutic
strategies. In the near future, additional strategies that target inflammation
could offer exciting new promise in the therapeutic approach to ICH.
PMID- 17033694
TI - Sustained neuronal activation raises oxidative metabolism to a new steady-state
level: evidence from 1H NMR spectroscopy in the human visual cortex.
AB - To date, functional 1H NMR spectroscopy has been utilized to report the time
courses of few metabolites, primarily lactate. Benefiting from the sensitivity
offered by ultra-high magnetic field (7 T), the concentrations of 17 metabolites
were measured in the human visual cortex during two paradigms of visual
stimulation lasting 5.3 and 10.6 mins. Significant concentration changes of
approximately 0.2 micromol/g were observed for several metabolites: lactate
increased by 23%+/-5% (P<0.0005), glutamate increased by 3%+/-1% (P<0.01),
whereas aspartate decreased by 15%+/-6% (P<0.05). Glucose concentration also
manifested a tendency to decrease during activation periods. The lactate
concentration reached the new steady-state level within the first minute of
activation and came back to baseline only after the stimulus ended. The changes
of the concentration of metabolites implied a rise in oxidative metabolism to a
new steady-state level during activation and indicated that amino-acid
homeostasis is affected by physiological stimulation, likely because of an
increased flux through the malate-aspartate shuttle.
PMID- 17033695
TI - Glutamate is preferred over glutamine for intermediary metabolism in cultured
cerebellar neurons.
AB - The glutamate-glutamine cycle is thought to be of paramount importance in the
mature brain; however, its significance is likely to vary with regional
differences in distance between astrocyte and synapse. The present study is aimed
at evaluating the role of this cycle in cultures of cerebellar neurons, mainly
consisting of glutamatergic granule cells. Cells were incubated in medium
containing [U-13C]glutamate or [U-13C]glutamine in the presence and absence of
unlabeled glutamine and glutamate, respectively. Cell extracts and media were
analyzed using high-performance liquid chromatography (HPLC) and gas
chromatography combined with mass spectrometry (GC/MS). Both [U-13C]glutamate and
[U-13C]glutamine were shown to be excellent precursors for synthesis of
neuroactive amino acids and tricarboxylic acid (TCA) cycle intermediates.
Labeling from [U-13C]glutamate was higher than that from [U-13C]glutamine in all
metabolites measured. The presence of [U-13C]glutamate plus unlabeled glutamine
in the experimental medium led to labeling very similar to that from [U
13C]glutamate alone. However, incubation in medium containing [U-13C]glutamine in
the presence of unlabeled glutamate almost abolished labeling of metabolites.
Thus, it could be shown that glutamate is the preferred substrate for
intermediary metabolism in cerebellar neurons. Label distribution indicating TCA
cycle activity showed more prominent cycling from [U-13C]glutamine than from [U
13C]glutamate. Labeling of succinate was lower than that of the other TCA cycle
intermediates, indicating an active role of the gamma-amino butyric acid shunt in
these cultures. It can be concluded that the cerebellar neurons rely more on
reuptake of glutamate than supply of glutamine from astrocytes for glutamate
homeostasis.
PMID- 17033696
TI - Generation of gene deletions and gene replacements in Escherichia coli O157:H7
using a temperature sensitive allelic exchange system.
AB - In this work we describe protocols for the generation of gene deletions and gene
replacements using a temperature sensitive plasmid in Escherichia coli O157:H7.
This technology requires flanking DNA to be cloned into a temperature sensitive
vector but the resulting clone allows great flexibility for further modification
of the target sequence. It is therefore highly suited to the study of genes in
which several rounds of changes are envisaged. A number of examples are used to
illustrate the flexibility of the system which has been used to create novel gene
replacements including fusions for protein localisation work and reporters for
transcriptional analyses. In this paper we describe protocols which can be used
with a high degree of success when applied to E. coli O157. The deletion and
replacement of the LEE4 operon of E. coli O157 is detailed to show the advantages
and limitations of the technology.
PMID- 17033697
TI - Chromatin immunoprecipitation assay detects ERalpha recruitment to gene specific
promoters in uterus.
AB - Chromatin immunoprecipitation (ChIP) technique allows detection of proteins that
bind to chromatin. While this technique has been applied extensively in cell
based studies, its tissue-based application remains poorly explored. We are
specifically interested in examining estrogen-dependent transcriptional mechanism
in respect of recruitment of estrogen receptor-alpha (ERalpha), a ligand
activated transcription factor, to uterine gene promoters in mice. Recent gene
array studies, utilizing ERalpha knock-out vs. wild-type mice, have revealed that
estrogen regulates numerous uterine genes temporally and most importantly via
ERalpha during the phase-II response, including three well characterized genes
viz., lactoferrin (Ltf), progesterone receptor (Pgr) and cyclinD1 (Ccnd1). Here,
utilizing systematic ChIP studies, we demonstrate endogenous recruitment of
ERalpha to above uterine gene promoters following estradiol-17beta (E(2))
injection in mice.
PMID- 17033698
TI - Combining genetic and biochemical approaches to identify functional molecular
contact points.
AB - Protein-protein interactions are required for many viral and cellular functions
and are potential targets for novel therapies. Here we detail a series of genetic
and biochemical techniques used in combination to find an essential molecular
contact point on the duck hepatitis B virus polymerase. These techniques include
differential immunoprecipitation, mutagenesis and peptide competition. The
strength of these techniques is their ability to identify contact points on
intact proteins or protein complexes employing functional assays. This approach
can be used to aid identification of putative binding sites on proteins and
protein complexes which are resistant to characterization by other methods.
PMID- 17033700
TI - Recent developments in the field of organic heterobimetallic compounds of the
alkaline-earth metals.
AB - Heterobimetallic compounds of the alkaline-earth metals show a wide structural
variety with strongly differing reactivity patterns. The combination of magnesium
and alkali metal amides yields cyclic molecules with an extreme high reactivity
which often are considered as "inverse crowns" with the metal atoms as
coordination sites for Lewis bases. In other metallates of the alkaline-earth
metals an activation of alkyl groups succeeds. In alkaline-earth metal zincates
an inverse coordination of the type M(2)[(mu-R)(2)ZnR](2) is observed and the
alkyl groups are in bridging positions between zinc and the s-block metals thus
forming a very reactive M-C-Zn three-center-two-electron bond. Furthermore, the
metals of the carbon group form alkaline-earth metal-silicon, -germanium and -tin
bonds or, in the presence of very strong Lewis bases, even solvent-separated ion
pairs. For electronegative substituents at tin an inverse coordination mode such
as M[(mu-R)(2)SnR](2) is observed.
PMID- 17033701
TI - Red-shifted luminescence from naphthalene-containing ligands due to pi-stacking
in self-assembled coordination cages.
AB - Incorporation of ligands containing substituted naphthalene cores into
coordination cages results in extensive aromatic pi-stacking between ligands;
this results in a red-shifted 'excimer-like' luminescence component from the
naphthyl groups compared to the free ligands, which is diagnostic of, and can be
used to monitor, cage assembly.
PMID- 17033699
TI - Addressing fluorogenic real-time qPCR inhibition using the novel custom Excel
file system 'FocusField2-6GallupqPCRSet-upTool-001' to attain consistently high
fidelity qPCR reactions.
AB - The purpose of this manuscript is to discuss fluorogenic real-time quantitative
polymerase chain reaction (qPCR) inhibition and to introduce/define a novel
Microsoft Excel-based file system which provides a way to detect and avoid
inhibition, and enables investigators to consistently design dynamically-sound,
truly LOG-linear qPCR reactions very quickly. The qPCR problems this invention
solves are universal to all qPCR reactions, and it performs all necessary qPCR
set-up calculations in about 52 seconds (using a pentium 4 processor) for up to
seven qPCR targets and seventy-two samples at a time - calculations that commonly
take capable investigators days to finish. We have named this custom Excel-based
file system "FocusField2-6GallupqPCRSet-upTool-001" (FF2-6-001 qPCR set-up tool),
and are in the process of transforming it into professional qPCR set-up software
to be made available in 2007. The current prototype is already fully functional.
PMID- 17033702
TI - Can an ancillary ligand lead to a thermodynamically stable end-on 1 : 1 Cu-O2
adduct supported by a beta-diketiminate ligand?
AB - The finding that dioxygen binds end-on to the Cu(B) site in the crystal structure
of a precatalytic complex of peptidylglycine alpha-hydroxylating monooxygenase
has spurred the search for biomimetic model complexes exhibiting the same
dioxygen coordination. Recent work has not only indicated that sterically
hindered beta-diketiminate ligands (L(1)) could support side-on 1 : 1 Cu-O(2)
adducts, but also that an end-on L(1)Cu(THF)O(2) structure occurs as an unstable
intermediate in the oxygenation mechanism of the Cu(I) complex. In this work,
density functional theory and multireference methods are used to determine the
potential of ancillary ligands, X, other than THF to yield thermodynamically
stable end-on L(1)CuXO(2) species. A diverse set of ligands X, comprising
phosphines, thiophene, cyclic ethers, acetonitrile, para-substituted pyridines, N
heterocyclic carbenes, and ligands bearing hydrogen bond donors, has been
considered in order to identify ligand characteristics which energetically favor
end-on L(1)CuXO(2) over: a) reversion to the Cu(I) complex and dioxygen, b)
isomerization to side-on L(1)CuXO(2), and c) decay to L(1)CuO(2) and X. Ancillary
ligands with judiciously chosen degrees and orientation of steric bulk and which
bear potential hydrogen bond donors to an end-on bound dioxygen moiety most favor
oxygenation of L(1)CuX to yield end-on L(1)CuXO(2). Conversion to the side-on
isomer can be deterred through the use of a sufficiently bulky ligand X, such as
one that is at least the size of a 5-membered ring. Loss of X to give L(1)CuO(2)
can be made prohibitively endergonic by employing ligands X which are highly
electron donating and which backbond strongly with and sigma-donate significantly
to copper.
PMID- 17033703
TI - Silver(I) complexation of linked 2,2'-dipyridylamine derivatives. Synthetic,
solvent extraction, membrane transport and X-ray structural studies.
AB - Synthesis of the 2,2'-dipyridylamine derivatives di-2-pyridylaminomethylbenzene
1, 1,2-bis(di-2-pyridylaminomethyl)benzene 2, 1,3-bis(di-2
pyridylaminomethyl)benzene 3, 2,6-bis(di-2-pyridylaminomethyl)pyridine 4, 1,4
bis(di-2-pyridylaminomethyl)benzene 5, and 1,3,5-tris(di-2
pyridylaminomethyl)benzene 6 are reported together with the single-crystal X-ray
structures of 2, 3, and 5. Reaction of individual salts of the type AgX (where X
= NO(3)(-), PF(6)(-), ClO(4)(-), or BF(4)(-)) with the above ligands has led to
the isolation of thirteen Ag(I) complexes, nine of which have also been
characterised by X-ray diffraction. In part, the inherent flexibility of the
respective ligands has resulted in the adoption of a range of coordination
arrangements. A series of liquid-liquid (H(2)O/CHCl(3)) extraction experiments of
Ag(I) with varying concentrations of 1-6 in the organic phase have been
undertaken, with the counter ion in the aqueous phase being respectively picrate,
perchlorate and nitrate. In general, extraction efficiencies for a given
ionophore followed the Hofmeister order of picrate > perchlorate > nitrate; in
each case the tris-dpa derivative 6 acting as the most efficient extractant of
the six systems investigated. Competitive seven-metal bulk membrane transport
experiments (H(2)O/CHCl(3)/H(2)O) employing the above ligands as the ionophore in
the organic phase and equimolar concentrations of Co(II), Ni(II), Zn(II), Cu(II),
Cd(II), Pb(II) and Ag(I) in the aqueous source phase were also undertaken, with
transport occurring against a pH gradient. Under the conditions employed 1 and 5
yielded negligible transport of any of the metals present in the source phase
while sole transport selectivity for Ag(I) was observed for 2-4 and 6.
PMID- 17033704
TI - The reaction of tertiary phosphines with (Ph2Se2I2)2--the influence of steric and
electronic effects.
AB - The reaction of (Ph(2)Se(2)I(2))(2) with a wide variety of tertiary phosphines
possessing different steric and electronic properties has been studied, leading
in most cases to R(3)PSe(Ph)I adducts; [R(3)P = (p-CH(3)C(6)H(4))(3)P (1), (m
CH(3)C(6)H(4))(3)P (2), (o-OCH(3)C(6)H(4))(3)P (4), Ph(2)MeP (6), Me(2)PhP (7),
Me(3)P (8), Cy(3)P (9)]. All of the products formed were characterised by
elemental analysis, Raman and multinuclear NMR spectroscopy. Both steric and
electronic factors are important in determining the structural motif (CT vs.
ionic) observed in the solid-state. In general, highly basic phosphines result in
a lengthening of the Se-I interaction, and a preference for an ionic structure.
The reaction with (o-CH(3)C(6)H(4))(3)P does not yield a stable R(3)PSe(Ph)I
adduct, and instead (o-CH(3)C(6)H(4))(3)PI(2) (3) is formed. The unusually long P
I bond, [2.5523(12) A], and short I-I bond, [3.0724(4) A], exhibited by is a
result of the high steric requirements of this phosphine. The similarly bulky (o
SCH(3)C(6)H(4))(3)P yields a mixture of (o-SCH(3)C(6)H(4))(3)PSe(Ph)I (5a) and
[(o-SCH(3)C(6)H(4))(3)PSePh]I(3) (5b). The crystal structures of (m
CH(3)C(6)H(4))(3)PSe(Ph)I, 2, (o-CH(3)C(6)H(4))(3)PI(2), 3, [(o
OCH(3)C(6)H(4))(3)PSePh]I.CH(2)Cl(2), 4, [(o-SCH(3)C(6)H(4))(3)PSePh]I(3), 5b,
two pseudo-polymorphs of Ph(2)MePSe(Ph)I, 6a/6b, and
[Me(3)PSe(Ph)I](2).CH(2)Cl(2), 8, are reported. The R(3)PSe(Ph)I adducts formed
exhibit one of four types of behaviour. Type I products, (such as 2) are CT in
the solid-state and display fluxionality in solution. Type II products (such as
6a/6b) lie close to the CT/ionic structural borderline, displaying long Se-I
bonds, and are more appropriately classified as [R(3)PSePh] (acceptor)/I(-)
(donor) CT complexes. Type II complexes ionise in solution to [R(3)PSePh]I. Type
III products, such as 8, are ionic in solution, but frequently show cation-anion,
or cation-solvent interactions in the solid-state, although these interactions
are weak and the linear P-Se-I motif is lost. Type IV products (such as 4) are
ionic and feature bulky phosphines. They display no short cation-anion
interactions in the solid-state.
PMID- 17033705
TI - Spectroelectrochemical evidence for communication within a laterally-bridged
dimanganese(III) bis-porphyrin.
AB - Electronic coupling between the porphyrin units of a laterally-bridged
dimanganese(III) bis-porphyrin 2 is explored using electrochemistry,
spectroelectrochemistry and resonance-Raman spectroscopy. It is found that strong
electronic interactions between the manganese(III) ion and the porphyrin
macrocycle enhance the perturbations experienced by these bis-porphyrin systems
when compared to related monomer porphyrin systems. In turn this leads to
effective electronic communication between the manganese ions in the bis
porphyrin. This finding has importance in the design of molecular wires based on
laterally-bridged oligo-metallo-porphyrins.
PMID- 17033706
TI - Synthesis and structures of acyclic monoanionic tetradentate aza beta
diketiminate complexes of magnesium, zinc, and cadmium.
AB - An acyclic monoanionic tetradentate nitrogen ligand was prepared through the
condensation of 2-(4-tolyl)-malondialdehyde and 8-aminoquinoline to give
(BDI(QQ))H where (BDI(QQ))H = (8-quinolyl)-NCHC(4-tolyl)CHNH-(8-quinolyl). Metal
complexes, (BDI(QQ))MX, were prepared where MX = MgBr 2, ZnCl 3, and CdOAc 4. The
spectroscopic and crystallographic properties of compounds 2, 3, and 4 were
explored. Structures of complexes 2, 3, 4, and the tridentate ligand, (BDI(Q))OH,
5, are reported.
PMID- 17033707
TI - Allosteric effects in asymmetric hydrogenation catalysis? Asymmetric induction as
a function of the substrate and the backbone flexibility of C1-symmetric
diphosphines in rhodium-catalysed hydrogenations.
AB - The new unsymmetrical, optically active ligands 1,2-C(2)H(4)(PPh(2))(2'R,5'R
2',5'-dimethylphospholanyl) (L(a)) and 1,3-C(3)H(6)(PPh(2))(2'R,5'R-2',5'
dimethylphospholanyl) (L(b)) form complexes of the type
[Rh(L)(cyclooctadiene)][BF(4)] where L = L(a) (1a) or L(b) (1b), [PtCl(2)(L)]
where L = L(a) (2a) or L(b) (2b) and [PdCl(2)(L)] where L = L(a) (3a) or Lb (3b).
The crystal structures of 2a and 2b show the chelate ligand backbones adopt delta
twist and flattened chair conformations respectively. Asymmetric hydrogenation of
enamides and dehydroaminoesters using 1a and 1b as catalysts show that the
ethylene-backboned diphosphine L(a) gives a more efficient catalyst in terms of
asymmetric induction than the propylene-backboned analogue L(b). The greatest
enantioselectivities were obtained with 1a and enamide substrates with ees up to
91%. Substrate-induced conformational changes in the Rh-diphosphine chelates are
proposed to explain some of the ees observed in the hydrogenation of enamides.
PMID- 17033708
TI - Thermodynamics and the structural aspects of the ternary complexes of Am(III),
Cm(III) and Eu(III) with Ox and EDTA + Ox.
AB - The stability constants and the associated thermodynamic parameters of formation
of the binary and the ternary complexes of Am(3+), Cm(3+) and Eu(3+) were
determined by a solvent extraction to measure the variation in the distribution
coefficient with temperature (0-60 degrees C) for aqueous solutions of I = 6.60 m
(NaClO(4)). The formation of ternary complexes is favored by both the enthalpy
(exothermic) and the entropy (endothermic) values. (13) C NMR, TRLFS and EXAFS
spectral data was used to study the coordination modes of the ternary complexes.
In the formation of the complex M(EDTA)(Ox)(3-), the EDTA retained all its
coordination sites with Ox binding via two carboxylates and with one water of
hydration remaining attached to the M(3+). In the complex M(EDTA)(Ox)(2)(5-), one
carboxylate, either from EDTA or Ox, is not bounded to M(3+) and there were no
water of hydration attached to these cations.
PMID- 17033709
TI - Complexes of 1,2-bis(aryl-imino)acenaphthene (Ar-BIAN) ligands with some heavy p
block elements.
AB - The new Ar-BIAN complexes [(mes-BIAN)InCl(3)(THF)] (1), [(mes-BIAN)(2)Tl][PF(6)]
(2), [(dipp-BIAN)SnCl(4)] (3), [(dipp-BIAN)SbCl(3)] (4), [(dipp-BIAN)BiCl(3)] (5)
and [(mes-BIAN)BiCl(3)] (6) have been prepared by treatment of the neutral mes-
and dipp-substituted BIAN ligands with the p-block reagents InCl(3), TlPF(6),
SnCl(4), SbCl(3), and BiCl(3). The molecular structures of complexes 1-6 have
been determined by single-crystal X-ray diffraction methods. However, only the
atom connectivity was established for 5.
PMID- 17033710
TI - Alkene cyclopropanation catalyzed by Halterman iron porphyrin: participation of
organic bases as axial ligands.
AB - With the iron(III) complex of the Halterman iron porphyrin [P*Fe(Cl)] and ethyl
diazoacetate (EDA) as catalyst and carbene source, respectively, styrene-type
substrates were converted to cyclopropyl esters with high trans/cis ratio (not
less than 12) and high enantioselectivity for the trans-isomers (74-86% ee). The
isomeric distribution of the cyclopropyl esters so obtained is akin to that
obtained from the previously reported Ru(II) counterpart [P*Ru(CO)]. A linear
Hammett correlation log(k(X)/k(H)) = sigma(+)rho was observed with rho = -0.57
suggesting the involvement of an electrophilic cyclopropanating species derived
from the iron(II) center as the reactive intermediate in the catalytic cycle.
This is further supported by a dramatic decrease in the enantioselectivity and
trans/cis ratio observed in an experiment of styrene cyclopropanation when the
reaction mixture was deliberately exposed to air. Axial ligand effects on the
selectivities was also investigated. Substantial improvement in trans/cis ratios
could be achieved by addition of organic bases such as pyridine (py) and 1
methylimidazole (MeIm) to the catalytic reaction. The existence of axially
ligated iron carbene moieties, [P*Fe(CHCO(2)Et)(py)] and [P*Fe(CHCO(2)Et)(MeIm)],
was established by electrospray mass spectrometry. Study of secondary kinetic
isotope effect indicated that a more product-like transition state was generated
by addition of MeIm.
PMID- 17033711
TI - Synthetic and structural comparisons of bismuth(III) carboxylates synthesised
under solvent-free and reflux conditions.
AB - Two synthetic approaches to the formation of bismuth(III) carboxylates have been
explored and compared. Ph(3)Bi was reacted with a series of carboxylic acids
(RCO(2)H) of varying pK(a) and functionality (R = PhCH[double bond, length as m
dash]CH, o-MeOC(6)H(4), m-MeOC(6)H(4), o-H(2)NC(6)H, o-O(2)NC(6)H(4), p
O(2)NC(6)H(4), 2-(C(5)H(4)N)) under reflux conditions in toluene and solvent
free. The thermochemical profiles of the solvent-free reactions were also studied
by DSC-TGA. All reactions produced the tri-substituted bismuth carboxylates in
comparable yields and purity with the exceptions of picolinic acid and p
nitrobenzoic acid. 2-Picolinic acid exclusively formed the di-substituted
complex, [PhBi(2-(C(5)H(4)N)CO(2))(2)](4), by both methods, while p-nitrobenzoic
acid gave the tri-substituted complex through reflux and the di-substituted
complex under solvent-free conditions. Two of the complexes were structurally
authenticated by single crystal X-ray diffraction: [PhBi(2
(C(5)H(4)N)CO(2))(2)](4) is tetrameric formed through five membered chelate rings
involving the pyridyl N and O(-C) rather than the less stable carboxylate (
CO(2)) chelates, while [Bi(o-MeOC(6)H(4)CO(2))(3)](infinity), is a polymer in
which dimeric units, constructed around two chelating and one unsymmetrical
bridging carboxylate on each Bi centre, are then joined together through longer
intermolecular Bi-O bridging bonds.
PMID- 17033712
TI - Quantitative determination of cucumber mosaic virus genome RNAs in virions by
real-time reverse transcription-polymerase chain reaction.
AB - A real-time RT-PCR procedure using the green fluorescent dye SYBR Green I was
developed for determining the absolute and relative copies of cucumber mosaic
virus (CMV) genomic RNAs contained in purified virions. Primers specific to each
CMV ORF were designed and selected. Sequences were then amplified with length
varying from 61 to 153 bp. Using dilution series of CMV genome RNAs prepared by
in vitro transcription as the standard samples, a good linear correlation was
observed between their threshold cycle (Ct) values and the logarithms of the
initial template amounts. The copies of genomic RNA 1, RNA 2, RNA 3 and the
subgenomic RNA 4 in CMV virions were quantified by this method, and the ratios
were about 1.00:1.17:3.58:5.81. These results were confirmed by Lab-on-a-chip and
northern blot hybridization assays. Our work is the first report concerning the
relative amounts of different RNA fragments in CMV virions as a virus with
tripartite genome.
PMID- 17033713
TI - Up-regulation of cartilage oligomeric matrix protein gene expression by insulin
like growth factor-I revealed by real-time reverse transcription-polymerase chain
reaction.
AB - Cartilage oligomeric matrix protein (COMP) strengthens cartilage by binding to
type II and type IX collagen-forming bridges between collagen fibrils. It was
hypothesized that perhaps one or more anabolic growth factors such as insulin
like growth factor-I (IGF-I), fibroblast growth factor-1 (FGF-1) or platelet
derived growth factor-BB (PDGF-BB) increase COMP gene expression. Their effects
on primary human chondrocytes and the chondrogenic cell line ATDC5 were studied
using real time reverse transcript-polymerase chain reaction (RT-PCR) for
quantification. IGF-I, but not the FGF-1 or PDGF-BB, up-regulated COMP gene
expression by approximate 5-fold in human adult chondrocytes in a dose- and time
dependent manner. IGF-I exerted similar effects on ATDC5 cells. Results from
these real time RT-PCR experiments were confirmed by transfecting into ATDC5
cells a full-length mouse COMP promoter cloned upstream of a luciferase reporter
gene. On stimulation with IGF-I, the luciferase reporter activity increased by
about eight times. In conclusion, IGF-I seems to be an important positive
regulator of COMP, which may play an important role in an attempted repair of
either traumatized or degenerated cartilage.
PMID- 17033714
TI - Immunological properties of recombinant Mycobacterium bovis bacillus Calmette
Guerin strain expressing fusion protein IL-2-ESAT-6.
AB - The live vaccine Mycobacterium bovis bacillus Calmette-Guerin (BCG) provides
variable efficacy against adult pulmonary tuberculosis (TB). Recombinant BCG,
expressing either immunodominant antigens or Th1 cytokines, is a promising
strategy for developing a new TB vaccine. However, not much is known about
whether the introduction of cytokine and specific antigen genes concurrently into
the BCG strain could improve the immunogenicity of BCG. In this study, a
recombinant BCG strain (rBCG) expressing the fusion protein human interleukin
(IL)-2 and ESAT-6 (early secreted antigenic target-6 kDa) antigen of
Mycobacterium tuberculosis was constructed. Six weeks after BALB/c mice (H-2d)
were immunized with 106 colony forming units (CFUs) BCG or rBCG, splenocyte
proliferation was determined with MTT [3-(4,5-dimethylthiazolyl-2)-2, 5
diphenyltetrazolium bromide] assay, IL-4 and interferon (IFN)-gamma produced by
splenocytes were tested by enzyme linked immunosorbent assay (ELISA,) and the
cytotoxicity of splenocytes from immunized mice to P815 cells (H-2d) expressing
ESAT-6 protein was measured using CytoTox 96 Non-Radioactive Cytotoxicity Assay.
Compared with native BCG-vaccinated mice, rBCG induced stronger Th1 responses
that were confirmed by high lymphoproliferative responses and IFN-gamma
production to culture filtrate protein (CFP) or ESAT-6 protein. Moreover, rBCG
induced significant enhanced CTL responses against P815-ESAT-6 cells. Results
from rBCG-immunized mice demonstrated that introducing the il-2 and esat-6 genes
into BCG could enhance Th1 type immune responses to ESAT-6. Further investigation
is needed by introducing other Th1 cytokines and antigens into BCG to optimize
the protective efficacy against TB.
PMID- 17033715
TI - Studies on the temperature effect on bacteriorhodopsin of purple and blue
membrane by fluorescence and absorption spectroscopy.
AB - Fluorescence and absorption spectra were used to study the temperature effect on
the conformation of bacteriorhodopsin (bR) in the blue and purple membranes
(termed as bRb and bRp respectively). The maximum emission wavelengths of
tryptophan fluorescence in both proteins at room temperature are 340 nm, and the
fluorescence quantum yield of bRb is about 1.4 fold higher than that of bRp. As
temperature increases, the tryptophan fluorescence of bRb decreases, while the
tryptophan fluorescence of bRp increases. The binding study of extrinsic
fluorescent probe bis-ANS indicated that the probe can bind only to bRb, but not
to bRp. These results suggest that significant structural difference existed
between bRb and bRp. It was also found that both kinds of bR are highly thermal
stable. The maximum wavelength of the protein fluorescence emission only shifted
from 340 nm to 346 nm at 100 degrees C. More interestingly, as temperature
increased, the characteristic absorption peak of bRb at 605 nm decreased and a
new absorption peak at 380 nm formed. The transition occurred at a narrow
temperature range (65 degrees C-70 degrees C). These facts indicated that an
intermediate can be induced by high temperature. This phenomenon has not been
reported before.
PMID- 17033716
TI - Expression of basic fibroblast growth factor results in the decrease of myostatin
mRNA in murine C2C12 myoblasts.
AB - During the development and regeneration of skeletal muscle, many growth factors,
such as basic fibroblast growth factor (bFGF, FGF-2) and myostatin, have been
shown to play regulating roles. bFGF contributes to promote proliferation and to
inhibit differentiation of skeletal muscle, whereas myostatin plays a series of
contrasting roles. In order to elucidate whether the expression of bFGF has any
relationship with the expression of myostatin in skeletal muscle cells, we
constructed a eukaryotic expression vector for the expression of exogenous bFGF
in murine C2C12 myoblasts. Quantitative RT-PCR assays indicated that with the
increase of the expression of exogenous bFGF gene, the expression of endogenous
myostatin gene was suppressed at mRNA level and protein level.
PMID- 17033717
TI - Bcl-XL small interfering RNA enhances sensitivity of Hepg2 hepatocellular
carcinoma cells to 5-fluorouracil and hydroxycamptothecin.
AB - Changes in drug sensitivity in Bcl-XL small interfering RNA (siRNA) transfected
Hepg2 hepatocellular carcinoma cells were investigated in this study. Bcl-XL
siRNA and negative siRNA expression vector were constructed and stably
transfected into Hepg2 cells. Reverse transcription (RT)-PCR, western blot and
immunofluorescence were used to detect the target gene expression at mRNA and
protein levels. Drug sensitivity of the cells to 5-fluorouracil (5-FU) and
hydroxycamptothecin (HCPT) were evaluated with MTT. The Bcl-XL mRNA and protein
expression levels in Bcl-XL siRNA transfectants were reduced compared with
negative siRNA transfectants or mock cells. MTT results showed that Bcl-XL siRNA
transfected cells have a higher cell inhibition rate than negative vector
transfected cells or untreated cells after treatment with 13, 130, 1300 and
13,000 mg/L of 5-FU. Bcl-XL siRNA transfected cells also showed increased drug
sensitivity compared with negative vector transfected cells or untreated cells
after treatment with 0.18, 0.36, 0.72 and 1.44 mg/L HCPT. Flow cytometry (FCM)
results demonstrated that the sub-G1 population increased in the Bcl-XL siRNA
group, compared with the negative siRNA group and untreated control group, after
the addition of 5-FU (1300 mg/L) and HCPT (0.72 mg/L). siRNA targeting Bcl-XL
gene can specifically down-regulate Bcl-XL expression in Hepg2 cells, and can
increase spontaneous cell apoptosis and sensitize cells to 5-FU or HCPT.
PMID- 17033718
TI - Model for unidirectional movement of axonemal and cytoplasmic dynein molecules.
AB - A model for the unidirectional movement of dynein is presented based on the
structural observations and biochemical experimental results available. In this
model, the binding affinity of dynein for microtubule (MT) is independent of its
nucleotide state and the change between strong and weak MT-binding is determined
naturally by the variation of relative orientation between the stalk and MT, as
the stalk rotates following nucleotide-state transition. Thus the enigmatic
communication from the adenosine triphosphate (ATP)-binding site in the globular
domain to the far MT-binding site in the tip of the stalk, which is a
prerequisite in conventional models, is not required. Using the present model,
the previous experimental results such as the effect of ATP and adenosine
diphosphate (ADP) bindings on dissociation of dynein from MT, the movement of
single-headed axonemal dyneins at saturating ATP concentration, the load
dependence of step-size for the movement of two-headed cytoplasmic dyneins and
the dependence of stall force on ATP concentration can be well explained.
PMID- 17033719
TI - Ubiquinone (coenzyme Q) biosynthesis in Chlamydophila pneumoniae AR39:
identification of the ubiD gene.
AB - Ubiquinone is an essential electron carrier in prokaryotes. Ubiquinone
biosynthesis involves at least nine reactions in Escherichia coli. 3-octaprenyl-4
hydroxybenzoate decarboxylase (UbiD) is an important enzyme on the pathway and
deletion of the ubiD gene in E. coli gives rise to ubiquinone deficiency in vivo.
A protein from Chlamydophila pneumoniae AR39 had significant similarity compared
with protein ubiD from E. coli. Based on this information, the protein-encoding
gene was used to swap its counterpart in E. coli, and gene expression in
resultant strain DYC was confirmed by RT-PCR. Strain DYC grew using succinate as
carbon source and rescued ubiquinone content in vivo, while ubiD deletion strain
DYD did not. Results suggest that the chlamydial protein exerts the function of
UbiD.
PMID- 17033720
TI - Establishment and application of a TaqMan real-time quantitative reverse
transcription-polymerase chain reaction assay for rubella virus RNA.
AB - The aim of this study was to establish and apply a real-time quantitative reverse
transcription-polymerase chain reaction (RT-PCR) for rubella virus (RV) RNA.
First, the primer and TaqMan probe concentrations, as well as reaction
temperatures were optimized to establish an efficient real-time quantitative RT
PCR assay for RV RNA. Next, an RV-specific PCR amplicon was made as an external
standard to estimate the linearity, amplification efficiency, analytical
sensitivity and reproducibility of the real time quantitative assay. Finally, the
assay was applied to quantify RV RNA in clinical samples for rubella diagnosis.
The RV-specific PCR amplicon was prepared for evaluation of the assay at 503 bp,
and its original concentration was 2.75x109 copies/mul. The real time
quantitative assay was shown to have good linearity (R2=0.9920), high
amplification efficiency (E=1.91), high sensitivity (275 copies/ml), and high
reproducibility (variation coefficient range, from 1.25% to 3.58%). Compared with
the gold standard, the specificity and sensitivity of the assay in clinical
samples was 96.4% and 86.4%, respectively. Therefore, the established
quantitative RT-PCR method is a simple, rapid, less-labored, quantitative, highly
specific and sensitive assay for RV RNA.
PMID- 17033721
TI - In vitro reassembly of tobacco ribulose-1,5-bisphosphate carboxylase/oxygenase
from fully denatured subunits.
AB - It has been generally proved impossible to reassemble ribulose-1,5-bisphosphate
carboxylase/oxygenase (Rubisco) from fully denatured subunits in vitro in higher
plant, because large subunit of fully denatured Rubisco is liable to precipitate
when the denaturant is removed by common methods of direct dilution and one-step
dialysis. In our experiment, the problem of precipitation was resolved by an
improved gradual dialysis method, which gradually decreased the concentration of
denaturant. However, fully denatured Rubisco subunits still could not be
reassembled into holoenzyme using gradual dialysis unless chaperonin 60 was
added. The restored activity of reassembled Rubisco was approximately 8% of
natural enzyme. The quantity of reassembled Rubisco increased greatly when heat
shock protein 70 was present in the reassembly process. ATP and Mg2+ were
unnecessary for in vitro reassembly of Rubisco, and Mg2+ inhibited the reassembly
process. The reassembly was weakened when ATP, Mg2+ and K+ existed together in
the reassembly process.
PMID- 17033722
TI - Self-reported lifetime physical activity and areal bone mineral density in
healthy postmenopausal women: the importance of teenage activity.
AB - Girls who exercise athletically have higher bone mass than their sedentary
counterparts, and this difference may be sustained in adulthood. However, whether
moderate physical activity during youth confers lasting benefits for bone is
unclear. We explored lifetime physical activity and current areal bone mineral
density (aBMD) in 78 postmenopausal women with no known history of osteoporosis.
Subjects reported physical activity for four age periods (12-18, 19-34, 35-49, >
or = 50 years) using the Historical Leisure Activity Questionnaire, completed two
3-day food records, had measurements of height and weight, and aBMD assessed
using dual-energy X-ray absorptiometry at the lumbar spine (L1-4) and proximal
femora. Low aBMD was detected at the lumbar spine in 43 (56%) women and at the
proximal femora in 38 (49%) women. Teenage physical activity, but not activity
during other age periods, was associated with current aBMD at both sites (lumbar
spine r = 0.31, P < 0.01; mean proximal femora r = 0.33, P < 0.01). Weight
bearing physical activity (WBPA) at age 12-18 years was the only predictor of
current lumbar spine aBMD (R (2) = 0.110, P = 0.004). Current proximal femoral
aBMD was positively predicted by physical activity at age 12-18 years and
negatively predicted by current age (R (2) = 0.175, P = 0.001). Subjects above
the median of teen WBPA had 5-8% higher current aBMD than those reporting less
teen WBPA and were less likely to be classified with osteopenia or osteoporosis.
Moderate physical activity during years of peak bone acquisition appears to have
lasting benefits for lumbar spine and proximal femoral aBMD in postmenopausal
women.
PMID- 17033723
TI - Ovine periodontal ligament stem cells: isolation, characterization, and
differentiation potential.
AB - Periodontal disease leads to destruction of the connective tissues responsible
for restraining teeth within the jaw. To date, various conventional therapies for
periodontal regeneration have shown limited and variable clinical outcomes.
Recent studies have suggested that newly identified human periodontal ligament
stem cells (PDLSCs) may offer an alternate and more reliable strategy for the
treatment of periodontal disease using a cell-based tissue engineering approach.
In the present study, we generated enriched preparations of PDLSCs derived from
ovine periodontal ligament using immunomagnetic bead selection, based on
expression of the mesenchymal stem cell-associated antigen CD106 (vascular cell
adhesion molecule 1). These CD106+ ovine PDLSCs demonstrated the capacity to form
adherent clonogenic clusters of fibroblast-like cells when plated at low
densities in vitro. Ex vivo-expanded ovine PDLSCs exhibited a high proliferation
rate in vitro and expressed a phenotype (CD44+, CD166+, CBFA-1+, collagen-I+,
bone sialoprotein+) consistent with human-derived PDLSCs. Furthermore, cultured
ovine PDLSCs expressed high transcript levels of the ligament/tendon-specific
early transcription factor scleraxis. Importantly, ex vivo-expanded ovine PDLSCs
demonstrated the capacity to regenerate both cementum-like mineral and
periodontal ligament when transplanted into NOD/SCID mice. The results from the
present study suggest that ovine PDLSCs may potentially be used as a novel
cellular therapy to facilitate successful and more predictable regeneration of
periodontal tissue using an ovine preclinical model of periodontal disease as a
prelude to human clinical studies.
PMID- 17033724
TI - Antiremodeling agents influence osteoblast activity differently in modeling and
remodeling sites of canine rib.
AB - Antiremodeling agents reduce bone loss in part through direct actions on
osteoclasts. Their effects on osteoblasts and bone formation activity are less
clear and may differ at sites undergoing modeling vs. remodeling. Skeletally
mature intact beagles, 1-2 years old at the start of the study, were treated
daily with clinically relevant doses of alendronate (0.10 or 0.20 mg/kg),
risedronate (0.05 or 0.10 mg/kg), raloxifene (0.50 mg/kg), or vehicle (1 mL/kg).
Dynamic bone formation parameters were histologically assessed on periosteal,
endocortical/trabecular, and intracortical bone envelopes of the rib. Raloxifene
significantly increased periosteal surface mineral apposition rate (MAR), a
measure of osteoblast activity, compared to all other treatments (+108 to +175%,
P < 0.02), while having no significant effect on MAR at either the
endocortical/trabecular or intracortical envelope. Alendronate (both 0.10 and
0.20 doses) and risedronate (only the 0.10 dose) significantly (P < or = 0.05)
suppressed MAR on the endocortical/trabecular envelope, while none of the
bisphosphonate doses significantly altered MAR at either the periosteal or
intracortical envelopes compared to vehicle. Based on these results, we conclude
that (1) at clinically relevant doses the two classes of antiremodeling agents,
bisphosphonates and selective estrogen receptor modulators, exert differential
effects on osteoblast activity in the canine rib and (2) this effect depends on
whether modeling or remodeling is the predominant mechanism of bone formation.
PMID- 17033725
TI - Identification of a promoter element within the zebrafish colXalpha1 gene
responsive to runx2 isoforms Osf2/Cbfa1 and til-1 but not to pebp2alphaA2.
AB - Type X collagen is a short chain collagen specifically expressed by hypertrophic
chondrocytes during endochondral ossification. We report here the functional
analysis of the zebrafish (Danio rerio) collagen Xalpha1 gene (colXalpha1)
promoter with the identification of a region responsive to two isoforms of the
runt domain transcription factor runx2. Furthermore, we provide evidence for the
presence of dual promoter usage in zebrafish, a finding that should be important
to further understanding of the regulation of its restricted tissue distribution
and spatial-temporal expression during early development. The zebrafish
colXalpha1 gene structure is comparable to that recently identified by
comparative genomics in takifugu and shows homology with corresponding mammalian
genes, indicating that its general architecture has been maintained throughout
vertebrate evolution. Our data suggest that, as in mammals, runx2 plays a role in
the development of the osteogenic lineage, supporting zebrafish as a model for
studies of bone and cartilage development.
PMID- 17033726
TI - Calvarial osteoclasts express a higher level of tartrate-resistant acid
phosphatase than long bone osteoclasts and activation does not depend on
cathepsin K or L activity.
AB - Bone resorption by osteoclasts depends on the activity of various proteolytic
enzymes, in particular those belonging to the group of cysteine proteinases. Next
to these enzymes, tartrate-resistant acid phosphatase (TRAP) is considered to
participate in this process. TRAP is synthesized as an inactive proenzyme, and in
vitro studies have shown its activation by cysteine proteinases. In the present
study, the possible involvement of the latter enzyme class in the in vivo
modulation of TRAP was investigated using mice deficient for cathepsin K and/or L
and in bones that express a high (long bone) or low (calvaria) level of cysteine
proteinase activity. The results demonstrated, in mice lacking cathepsin K but
not in those deficient for cathepsin L, significantly higher levels of TRAP
activity in long bone. This higher activity was due to a higher number of
osteoclasts. Next, we found considerable differences in TRAP activity between
calvarial and long bones. Calvarial bones contained a 25-fold higher level of
activity than long bones. This difference was seen in all mice, irrespective of
genotype. Osteoclasts isolated from the two types of bone revealed that calvarial
osteoclasts expressed higher enzyme activity as well as a higher level of mRNA
for the enzyme. Analysis of TRAP-deficient mice revealed higher levels of
nondigested bone matrix components in and around calvarial osteoclasts than in
long bone osteoclasts. Finally, inhibition of cysteine proteinase activity by
specific inhibitors resulted in increased TRAP activity. Our data suggest that
neither cathepsin K nor L is essential in activating TRAP. The findings also
point to functional differences between osteoclasts from different bone sites in
terms of participation of TRAP in degradation of bone matrix. We propose that the
higher level of TRAP activity in calvarial osteoclasts compared to that in long
bone cells may partially compensate for the lower cysteine proteinase activity
found in calvarial osteoclasts and TRAP may contribute to the degradation of
noncollagenous proteins during the digestion of this type of bone.
PMID- 17033727
TI - Desorption of arsenic from drinking water distribution system solids.
AB - Previous work has shown that arsenic can accumulate in drinking water
distribution system (DWDS) solids (Lytle et al., 2004) when arsenic is present in
the water. The release of arsenic back into the water through particulate
transport and/or chemical release (e.g. desorption, dissolution) could result in
elevated arsenic levels at the consumers' tap. The primary objective of this work
was to examine the impact of pH and orthophosphate on the chemical release (i.e.
desorption) of arsenic from nine DWDS solids collected from utilities located in
the Midwest. Arsenic release comparisons were based on the examination of arsenic
and other water quality parameters in leach water after contact with the solids
over the course of 168~hours. Results showed that arsenic was released from
solids and suggested that arsenic release was a result of desorption rather than
dissolution. Arsenic release generally increased with increasing initial arsenic
concentration in the solid and increasing pH levels (in the test range of 7 to
9). Finally, orthophosphate (3 and 5 mg PO(4)/L) increased arsenic release at all
pH values examined. Based on the study results, utilities with measurable levels
of arsenic present in their water should be aware that some water quality changes
can cause arsenic release in the DWDS potentially resulting in elevated levels at
the consumer's tap.
PMID- 17033728
TI - Multislice computed tomographic findings of the anomalous origins of the right
coronary artery: evaluation of possible causes of myocardial ischemia.
AB - BACKGROUND: Anomalous right coronary arteries (RCA) arising from the left sinus
of Valsalva may cause myocardial ischemia. OBJECTIVE: We evaluated morphological
features of anomalous RCA by using multislice computed tomography (MSCT) in
relation to myocardial ischemia provoked by myocardial perfusion single-photon
emission computed tomography. METHODS: MSCT was performed in a total of 3, 212
patients by using an Aquillion 16 and a Light Speed Ultra. Retrospective ECG
gated image reconstruction was performed. Volume rendering, axial and curved
multiplanar reformatted images were analyzed for the determination of the origin
and course of the RCA, the take-off angle of the RCA from the aorta, and size of
the RCA orifice. Furthermore, virtual angioscopic images were also used for the
evaluation of the RCA orifice structure. RESULTS: Anomalous origins of the RCA
were found in 15 patients. In 13 patients, the RCA arose from the left sinus of
Valsalva, and in 2 patients it arose from the left main coronary artery as a
single coronary artery. The RCA coursed anteriorly between the ascending aorta
and pulmonary artery in 14 patients, whereas it had a retroaortic course in 1
patient. Acute angle take-off (<30 degrees ) of the RCA from the aorta and the
left main coronary artery was observed in 8 patients, intramural course of the
RCA within the aortic wall was observed in 6 patients and a small RCA orifice was
observed in 4 patients. Exercise-induced myocardial ischemia was present in 5
patients. CONCLUSION: Coursing between the aorta and pulmonary artery, acute
angle take-off and intramural course were thought to be major causes of exercise
induced ischemia in patients with anomalous origins of the RCA.
PMID- 17033729
TI - Sustainability in the cardiac cath lab.
AB - Use of radiation for medical examinations and test is the largest man-made source
of radiation exposure. Interventional procedures are only 2% of all radiological
procedures, but contribute to about 20% of the total collective dose per head per
year. On average, a left ventriculography and coronary angiography corresponds to
a radiation exposure for the patient of about 300, a coronary stent to 1,000, a
peripheral artery intervention to 1,500 to 2,500, and a cardiac radiofrequency
ablation to 900-1,500 chest x-rays. Invasive cardiology procedures increased
tenfold in the last ten years and growth in the field has been accompanied by
concern for the safety of the staff. Interventional cardiologists have an
exposure per-head per year two- to three times higher than that of radiologists,
with an annual exposure equivalent to around 250 chest x-rays per head. A
reduction of occupational doses by a factor of ten can be achieved simply by and
intensive training program. The awareness of radiation effects may be suboptimal
in the medical community. It is recommended by professional guidelines and
reinforced by the European law that the responsibility of all physicians is to
minimize the radiation injury hazard to their patients, to their professional
staff and to themselves.
PMID- 17033730
TI - Thoracoabdominal aorta coarctation with bilateral renal artery involvement:
diagnosis with multidetector CT angiography (MDCTA).
AB - Atypical coarctation of the descending thoracic and abdominal aorta is a very
uncommon vascular disease. Congenital, acquired, inflammatory, and infectious
etiologies have been proposed. Patients typically presents with uncontrolled
secondary hypertension in the upper half of the body or hypotension in the lower
extremities in the first three decades of their lives. We report the case of a 20
year-old man with severe hypertension. Diffuse coarctation of thoracoabdominal
aorta associated with bilateral renal artery stenosis was demonstrated clearly by
multidetector CT angiography. This is the first case of atypical aortic
coarctation diagnosed by MDCTA.
PMID- 17033731
TI - DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a
single-nucleotide polymorphism microarray: standardization of molecular
investigations of genetic diseases due to consanguinity.
AB - Malignant osteopetrosis, a severe disease causing early infantile death in
humans, is caused by mutations in the TCIRG1, CLCN7, or OSTM1 genes. We have
established the molecular basis of malignant osteopetrosis in a Chinese family by
means of whole-genome scans based on high-density single-nucleotide polymorphism
(SNP) microarrays. Because the parents were consanguineous, the disease-causing
locus should be located in an autozygous chromosomal region. Mapping revealed
that among the three possible causal loci, only the CLCN7 gene was located in an
autozygous region. Mutational analysis of the CLCN7 gene showed that the proband
was homozygous for a novel missense mutation, p.I261F. p.I261 is located in helix
F of the chloride channel, near a critical site for gating of the channel. This
mapping study prepares the ground for future mutation studies by decreasing the
burden of completely sequencing all possible loci for this disease. This approach
can be used to standardize molecular investigations of genetic diseases due to
consanguinity to a whole-genome scan and subsequent sequencing of the mapped
disease gene.
PMID- 17033732
TI - Ankyrin G overexpression in Hutchinson-Gilford progeria syndrome fibroblasts
identified through biological filtering of expression profiles.
AB - Hutchinson-Gilford progeria syndrome (HGPS; MIM 176670) is a rare disease
characterized by accelerated aging. In this study, light and immunofluorescence
microscopy were used to assess morphological changes, measures of cell growth
kinetics and gene expression profiles in HGPS cells and normal fibroblasts in
culture. A filtering strategy was developed based on differentially expressed
transcripts seen consistently across three culture stages based on cell passage
number. This filtering strategy produced a list of 66 unique differentially
expressed genes, of which approximately 40% were upregulated in HGPS cells
compared to normal fibroblasts. The increased mRNA expression in HGPS cells that
was seen for one gene defined using this strategy--namely ANK3--was validated
using quantitative reverse-transcriptase amplification, Western analysis and
immunofluorescence microscopy, all of which showed significantly increased
ankyrin G expression. These findings demonstrate differences in morphology,
growth kinetics and mRNA expression profiles in HGPS cells compared to normal
fibroblasts in culture, including increased expression of ANK3/ankyrin G.
Furthermore, other genes that co-clustered with ANK3 might provide mechanistic
clues regarding senescence in cultured HGPS cells.
PMID- 17033733
TI - Gene cloning and expression in Escherichia coli of a bi-functional beta-D
xylosidase/alpha-L-arabinosidase from Sulfolobus solfataricus involved in xylan
degradation.
AB - An open reading frame encoding a putative bi-functional beta-D-xylosidase/alpha-L
arabinosidase (Sso3032) was identified on the genome sequence of Sulfolobus
solfataricus P2, the predicted gene product showing high amino-acid sequence
similarity to bacterial and eukaryal individual beta-D-xylosidases and alpha-L
arabinosidases as well as bi-functional enzymes such as the protein from
Thermoanaerobacter ethanolicus and barley. The sequence was PCR amplified from
genomic DNA of S. solfataricus P2 and heterologous gene expression obtained in
Escherichia coli, under optimal conditions for overproduction. Specific assays
performed at 75 degrees C revealed the presence in the transformed E. coli cell
extracts of this archaeal activity involved in sugar hydrolysis and specific for
both substrates. The recombinant protein was purified by thermal precipitation of
the host proteins and ethanol fractionation and other properties, such as high
thermal activity and thermostability could be determined. The protein showed a
homo-tetrameric structure with a subunit of molecular mass of 82.0 kDa which was
in perfect agreement with that deduced from the cloned gene. Northern blot
analysis of the xarS gene indicates that it is specifically induced by xylan and
repressed by monosaccharides like D-glucose and L-arabinose.
PMID- 17033735
TI - Radiologic anatomy of the superior mesenteric vein and branching patterns of the
first jejunal trunk: evaluation using multi-detector row CT venography.
AB - The purpose of this study was to describe radiologic anatomy of the superior
mesenteric vein (SMV) and to evaluate branching patterns of the first jejunal
trunk on axial CT images and multi-detector row CT (MDCT) venography in adults.
Two hundred and twenty consecutive patients who underwent abdominal CT
examinations were enrolled in this study. Appearance of the SMV, branching
patterns of the first jejunal trunk, and drainage site of the inferior mesenteric
vein (IMV) were assessed on axial CT images and MDCT venography. The SMV and
first jejunal trunk were identified in all patients. A single trunk of the SMV
was present in 95% (210/220) and absent in 5% (10/220). First jejunal trunk
crossed dorsal to the superior mesenteric artery (SMA) towards the left abdomen
in 64% (141/220) and first jejunal trunk crossed ventral to the SMA in 19%
(41/220). First jejunal trunk crossed dorsal to the SMA and abruptly turned
towards the right abdomen in 17% (38/220). Among these 38 patients, biliary
enteric bypass surgery (n = 9) and large hematoma in left abdomen (n = 1) were
present. The IMV was identified in 213 patients and was observed to drain into
splenic vein in 112 patients (53%), SMV in 67 (31%), splenoportal confluence in
26 (12%), and first jejunal trunk in 8 (4%). In conclusion, the first jejunal
trunk, abruptly turning toward the right abdomen, may be an anatomic variant or
indirect finding of biliary-enteric anastomosis. The IMV may drain into the first
jejunal trunk as well as splenic vein, splenoportal confluence, and SMV.
PMID- 17033734
TI - Human pelvic extramural ganglion cells: a semiquantitative and
immunohistochemical study.
AB - In pelvic surgery, much attention is paid to nerve bundles but not to ganglion
cells. Using serial section histology of 14 postmortem-treated hemipelvis (eight
males, six females; mean, 79 years old), we examined the population number,
distribution, and tyrosine hydroxylase-immunoreactivity (TH-IR; suggesting
sympathetic neurons) of extramural pelvic ganglion cells. All pelvic ganglion
cells were uniformly sized (25-30 microm) contrasting with small intramural
rectal neurons. Abundant ganglion cells (30,000-140,000 unilaterally) existed not
only along the pelvic viscera except for the rectum, but also along the
hypogastric nerve, pelvic splanchnic nerve, pelvic plexus, and associated
branches excluding those within the mesorectum. The intrapelvic ganglion cells
outside the sympathetic trunk did not form macroscopically identifiable ganglia,
but made small clusters (0.1-2.0 mm of maximum diameter) or were diffusely
scattered within nerve bundles. More than half of these cells appeared TH-IR
positive, although the positive/negative proportion differed between nerves and
specimens. Greater numbers of ganglion cells were found in dorsosuperior sites
(e.g., around the seminal vesicle) rather than in ventroinferior sites (e.g.,
along the urethra) in males, and vice versa in females. However, in total cell
numbers, interindividual variations were evident rather than intergender
difference. Due to significant interindividual variations in cell number,
differences are likely to exist between patients in "resistance" to surgical
stresses. We hypothesized that pelvic ganglion cells are liable to be damaged due
to drying along the surgical margin, hypoxia in venous bleeding, pressure from
surgical retractors, extension stress with taping and excess traction and/or
direct injury with electrical scalpels.
PMID- 17033736
TI - CT differentiation of distal pancreas fat replacement and distal pancreas
agenesis.
AB - We aimed to describe CT signs useful for differentiation of distal agenesis from
distal or dorsal pancreas lipomatosis. Multidetector CT (MDCT) studies of five
patients with distal pancreas agenesis (n = 2), distal lipomatosis (n = 1),
distal short pancreas (n = 1), and distal pancreatectomy (n = 1) were
retrospectively reviewed. Agenesis of dorsal pancreas can be diagnosed by the
absence of body and tail of pancreas. In the absence of distal pancreas, distal
pancreatic bed can be filled by stomach or intestine (dependent stomach or
dependent intestine signs), which abut splenic vein. Same findings can be seen in
patients with distal pancreatectomy, however, splenic vein is absent in these
patients. In case of distal lipomatosis abundant fat tissue is observed anterior
to splenic vein. Dependent stomach and/or dependent intestine signs on MDCT
imaging can allow differentiation of distal pancreas agenesis from distal
lipomatosis obviating further diagnostic studies.
PMID- 17033737
TI - Anxiety disorders among Nigerian women in late pregnancy: a controlled study.
AB - This study aimed to investigate the rate and type of anxiety disorders among
Nigerian women in late pregnancy. Women in late pregnancy (n = 172) and a non
pregnant control group were assessed for DSM-IV anxiety disorders. The rate of
any anxiety disorder in the pregnant women was 39.0% compared with 16.3% in the
non-pregnant population (p < 0.001). Although all the anxiety disorders were more
common, only the rate of social anxiety disorder was significantly higher among
the pregnant than non-pregnant population. Correlates of anxiety disorder in the
pregnant population include age less than 25 years (OR 4.62, 95% CI 2.39-8.92),
primiparity (OR 3.90, 95% CI 2.00-7.59) and presence of medical conditions (OR
3.60, 95% CI 1.28-10.12). More research is needed in this field to ascertain the
specific association between pregnancy and anxiety disorders.
PMID- 17033738
TI - Intimate partner violence and health outcomes in mid-life women: a population
based cohort study.
AB - AIM: To investigate the association between experience of intimate partner
violence (IPV) and health outcomes measured prospectively. METHOD: Eleven-year
prospective study of a population-based cohort of 438 Australian-born women aged
45-55 years at baseline (in 1991). Annual face-to-face interviews measured health
status and quality of life; questionnaires on intimate partner physical,
emotional and sexual violence and on experiences of childhood abuse completed in
year 6 of follow-up. RESULTS: In year 11 of follow-up 233 women (mean age 59.9 SD
2.5 years) were interviewed of whom 62 (27%) reported experiencing physical
and/or emotional and/or sexual IPV prior to the 6(th) year of follow-up. In bi
variate analysis a history of IPV was significantly associated with mental and
sexual health variables and marital status at baseline and follow-up.
Multivariate analysis found that at follow-up after allowing for baseline
measures and other co-variates: Frequency of Sexual Activities was lower in women
who had experienced IPV (p < 0.05); and negative mood was higher in women with
the experience of IPV during the 12 months prior to completing the violence
questionnaire (p < 0.05). CONCLUSION: IPV was a significant contributor to mental
and sexual health status measured prospectively in this cohort of mid-aged
Australian-born women.
PMID- 17033739
TI - Prevalence and psychosocial correlates of depressed mood during pregnancy and
after childbirth in a Moroccan sample.
AB - The objective of the current study was to determine the prevalence of depression
among 100 women followed from the first trimester of pregnancy to 9 months after
delivery. Mini International Neuropsychiatric Interview, Edinburgh Postnatal
Depression Scale and Paykel Life Events Inventory were used. Seventeen per cent
of the subjects experienced depression during postpartum, 19.2% started their
episode during pregnancy. Psychosocial variables were positively correlated to
depression during pregnancy.
PMID- 17033740
TI - Does maternal psychopathology discriminate between children with DSM-IV
generalised anxiety disorder or oppositional defiant disorder? The predictive
validity of maternal axis I and axis II psychopathology.
AB - What dimensions of maternal psychopathology predict internalising or
externalising disorder in children? We conducted a study of maternal axis I and
axis II psychopathology in a group of children 8-12 years of age with Generalised
Anxiety Disorder (GAD), Oppositional Defiant Disorder (ODD) and non-patient
controls (NC). By using Multigroup Discriminant Analyses (MDA) on three groups of
children (N = 85) and measures of axis I and axis II psychopathology of their
mothers, we attempted to discriminate between these groups on a data driven
basis. Two separate MDA were computed, one based on maternal axis I disorders,
and one based on maternal axis II disorders. The results demonstrated that
maternal symptomatic and personality psychopathology was differentially related
to childhood anxiety or behavioural disorders. Mothers of children with ODD were
characterised by more negative emotions and detached personality styles, whereas
mothers of children with GAD seemed to be more somatic preoccupied, controlling
and over-protective.
PMID- 17033741
TI - Cellular and matrix mechanics of bioartificial tissues during continuous cyclic
stretch.
AB - Bioartificial tissues are useful model systems for studying cell and extra
cellular matrix mechanics. These tissues provide a 3D environment for cells and
allow tissue components to be easily modified and quantified. In this study, we
fabricated bioartificial tissue rings from a 1 ml solution containing one million
cardiac fibroblasts and 1 mg collagen. After 8 days, rings compacted to <1% of
original volume and cell number increased 2.4 fold. We initiated continuous
cyclic stretching of the rings after 2, 4, or 8 days of incubation, while
monitoring the tissue forces. Peak tissue force during each cycle decreased
rapidly after initiating stretch, followed by further slow decline. We added 2
microM Cytochalasin-D to some rings prior to initiation of stretch to determine
the force contributed by the matrix. Cell force was estimated by subtracting
matrix force from tissue force. After 12 h, matrix force-strain curves were
highly nonlinear. Cell force-strain curves were linear during loading and showed
hysteresis indicating viscoelastic behavior. Cell stiffness increased with
stretching frequency from 0.001-0.25 Hz. Cell stiffness decreased with stretch
amplitude (5-25%) at 0.1 Hz. The trends in cell stiffness do not fit simple
viscoelastic models previously proposed, and suggest possible strain-amplitude
related changes during cyclic stretch.
PMID- 17033742
TI - Low-level laser therapy can reduce lipopolysaccharide-induced contractile force
dysfunction and TNF-alpha levels in rat diaphragm muscle.
AB - Our objective was to investigate if low-level laser therapy (LLLT) could improve
respiratory function and inhibit tumor necrosis factor (TNF-alpha) release into
the diaphragm muscle of rats after an intravenous injection of lipopolysaccharide
(LPS) (5 mg/kg). We randomly divided Wistar rats in a control group without LPS
injection, and LPS groups receiving either (a) no therapy, (b) four sessions in
24 h with diode Ga-AsI-Al laser of 650 nm and a total dose of 5.2 J/cm2, or (c)
an intravenous injection (1.25 mg/kg) of the TNF-alpha inhibitor chlorpromazine
(CPZ). LPS injection reduced maximal force by electrical stimulation of diaphragm
muscle from 24.15+/-0.87 N in controls, but the addition of LLLT partly inhibited
this reduction (LPS only: 15.01+/-1.1 N vs LPS+LLLT: 18.84+/-0.73 N, P<0.05). In
addition, this dose of LLLT and CPZ significantly (P<0.05 and P<0.01,
respectively) reduced TNF-alpha concentrations in diaphragm muscle when compared
to the untreated control group.
PMID- 17033743
TI - An evaluation of the effect of a gastric ischemia-reperfusion model with laser
Doppler blood perfusion imaging.
AB - The objectives of this study are to establish a gastric ischemia-reperfusion
model and test it using the laser Doppler blood perfusion imaging (LDPI) method
and to evaluate the role of the LDPI technique in the measure of gastric blood
circulation. The right gastric artery of the rat was clamped for 30 min and then
reperfused. The LDPI was used to display the blood circulation of the whole
gastric surface during this process. The blood flow perfusion image of the
gastric surface was displayed clearly. After the right gastric artery was
clamped, the blood flow perfusion on the gastric surface decreased very
significantly until the clamp was loosened. Following reperfusion, the blood flow
suddenly increased. Within the first 10 min, the blood-flow perfusion exceeded
the level before the clamping and then gradually became smooth and steady. The
right gastric artery is a main pathway for gastric blood supply. LDPI can display
successfully the blood circulation state of the stomach and the course of
ischemia-reperfusion of a large area with an image.
PMID- 17033745
TI - Five years after 9/11-fearing smallpox, ... and the vaccine against it.
PMID- 17033746
TI - Estimation of the duration of vaccine-induced residual protection against severe
and fatal smallpox based on secondary vaccination failure.
AB - BACKGROUND: Understanding the loss of vaccine-induced immunity against smallpox
is essential in determining the fraction of those who are still protected in the
present population and in constructing effective countermeasures against
bioterrorist attacks. METHOD: Three small Australian outbreaks from the 1880s to
early 1900s were investigated. Each documented individual age at infection. The
case records for Launceston, 1903, further documented the age at vaccination and
disease severity, enabling estimates of the duration of protection against severe
and fatal smallpox. RESULTS: A significant association between vaccination and
death was observed in the outbreak in Sydney, 1881 (odds ratio of death among
vaccinated individuals = 0.3; 95% confidence interval (CI): 0.1, 0.8; p = 0.02),
where the time since last vaccination was similar for all vaccinated cases. In
Launceston, 1903, where the age at vaccination varied widely, the median duration
of partial protection against severe and fatal smallpox was estimated to be 31.7
(95% CI: 13.2, 116.2) and 53.9 (95% CI: 25.6, 123.5) years after vaccination,
respectively. Whereas those in their 20s are expected to have the highest
frequency of vulnerability to smallpox death in the present population,
infections among those in their 30s or 40s are expected to be much less fatal.
CONCLUSION: Long lasting partial protection was suggested from the outbreak
records, the estimated durations of which were roughly consistent with those
reported previously. In the event of a bioterrorist attack, those involved in
emergency tasks before emergency vaccination practices are re-established should
ideally be previously vaccinated individuals in their 30s or 40s.
PMID- 17033747
TI - Postneurosurgical nosocomial bacterial brain abscess in adults.
AB - BACKGROUND: Bacterial brain abscess after a neurosurgical procedure has become an
important occurrence in the hospital setting. However, no information about the
frequency, clinical relevance, and the outcome has been reported. PATIENTS AND
METHODS: Over a period of 19 years (1986- 2004), a total of 31 patients were
retrospectively identified as having brain abscesses after neurosurgical
procedures and were enrolled in this study. RESULTS: Those included in this study
accounted for 0.17% (31/18600) of all neurosurgical procedures in the same
period. There was an increased percentage of adult postneurological nosocomial
brain abscess compared to all adult bacterial brain abscesses in recent years.
The majority of cases were due to Gram-negative bacilli and polymicrobial
infections, including both Gram-negative bacilli and Staphylococcus species.
Furthermore, the appearance of multi-antibiotic resistant strains was also noted
during the study period. The overall fatality rate was 16%. CONCLUSION: Post
neurosurgical states have become important predisposing factor for bacterial
brain abscess. In patients that undergo neurosurgical procedures and develop
smoldering fever, progressively disturbed consciousness, headache, and new onset
focal neurologic signs, immediate neuro-imaging studies should be undertaken to
determine whether bacterial brain abscess is present. Although mortality may be
related to the primary brain pathology, early diagnosis and timely use of
appropriate antibiotics based on antimicrobial susceptibility testing are also
essential for survival.
PMID- 17033748
TI - Enterobacter bacteremia: Clinical features, risk factors for multiresistance and
mortality in a Chinese University Hospital.
AB - BACKGROUND: This study was performed to characterize the clinical features and to
identify the risk factors for multiresistance and mortality in patients with
Enterobacter bacteremia. PATIENTS AND METHODS: A number of 126 patients with
Enterobacter bacteremia in 1995-2004 at the Medical university-affiliated
Hospital of Anhui, China were retrospectively analyzed. RESULTS: Of the 126 cases
of bacteremia, 81 (64.3%) patients were identified as nosocomial infection. The
overall multiresistance rate was 45.2% (57/126). Multiresistance was associated
with nosocomial infection, recent invasive procedure, previous third-generation
cephalosporins therapy, prolonged perioperative prophylaxis, the species of
Enterobacter (E. cloacae) and polymicrobial bacteremia in univariate analysis. In
multivariate analysis, previous third-generation cephalosporins therapy (OR =
13.6, p = 0.007) and prolonged perioperative prophylaxis (OR = 6.4, p = 0.029)
were the strong, independent risk factors for the multiresistance. The crude 30
day mortality rate was 39.7% (50/126). Mortality directly attributed to
Enterobacter spp. was 32.5% (41/126), which was significantly associated with
multiresistance, nosocomial infection, recent invasive procedure, and
inadequately empirical therapy in univariate analysis. Multivariate analysis
revealed that only nosocomial infection (OR = 3.292, p = 0.049) was independently
associated with mortality. The survival curve showed that the inappropriate
initial therapy group had a lower probability of survival than the appropriate
therapy group in infection-related mortality (Log Rank, p = 0.0142). CONCLUSION:
Enterobacter is becoming increasingly important nosocomial pathogens. Nosocomial
infection is a clinical risk factor tightly associated with multiresistance and
worse outcome. More judicious use of third-generation cephalosporins may decrease
the incidence of nosocomial multiresistant Enterobacter spp. in China.
PMID- 17033749
TI - Influence of prolonged use of intravenous administration sets in paediatric
cancer patients on CVAD-related bloodstream infection rates and hospital
resources.
AB - BACKGROUND: To assess the effects of extending the routine intravenous
administration set (IVAS) change-interval from 72 h (group 1) to 7 days (group 2)
on the incidence density for central venous access device (CVAD)-related
bloodstream infections (BSIs) and on resource expenditures in a singlecentre
pilot study. PROCEDURE: Prospective pre-/post-intervention comparison of two
consecutive 12-month surveillance periods (2001-2003) in a 17-bed paediatric
oncology tertiary care unit. IVAS changes and nosocomial infections (NIs) were
prospectively analysed using a standardized unit-based surveillance system
(Oncopaed NI). RESULTS: All 175 eligible patients were enrolled, 96 in group 1
and 79 in group 2. Both groups had similar distributions of primary diagnoses and
risk factors. The proportion of IVAS changes performed after 3 days increased
from 5.6% to 22.5%, but only 8% of IVASs in group 2 were changed after 7 days.
Most IVAS changes (64.8% in group 1 and 92.9% in group 2) were done because of
therapeutic interventions (blood products, parenteral nutrition [TNP]) before the
scheduled endpoint. Overall, the rates and incidence densities of NIs were
significantly lower during the second period. The corresponding results for CVAD
related BSIs did not show significant differences. No death attributable to a NI
occurred. The '7-day' strategy resulted in cost savings for devices (3,300
dollars/year) and of nursing time (23 working days/year). CONCLUSIONS: Extending
the routine IVAS change-interval from 3 days to 7 days appears to be safe and
cost-effective in a paediatric oncology unit with high infection control
standards and continuous surveillance for NIs. These results do not prove that 7
day intervals prevent infections, but they do suggest that this policy probably
is not harmful and that a prospectively randomized study with sufficient power is
needed.
PMID- 17033750
TI - Detection of legionella species in clinical samples: Comparison of polymerase
chain reaction and urinary antigen detection kits.
AB - BACKGROUND: Recently, two excellent methods have been used for the diagnosis of
Legionnaires' disease: urinary antigen detection and PCR. The purpose of the
present study is to analyze and evaluate the sensitivity and specificity of three
different urinary antigen detection kits as well as PCR. MATERIALS AND METHODS: A
total of 148 samples were collected from 33 patients between 1993 and 2004. These
consisted of 73 urine samples obtained from 33 patients, 57 serum samples
provided by 29 patients, and 18 respiratory tract specimens from 13 patients.
Three commercially available kits were used to detect urinary antigen. For the 5S
PCR reaction, primers L5SL2 and L5SR84 were used. RESULTS: Positive results were
shown in all patients' urine (representing 79.5% of total samples) using the
Binax EIA kit, in 93.9% patients (representing 75.3% samples) using the Binax NOW
immunochromatographic kit, and in 90.9% (representing 72.6% samples) using the
Biotest EIA kit. Urine samples from 12.1% patients (representing 6.8% of total
samples), serum samples from 41.4% patients (representing 35.1% of total
samples), and respiratory samples from 84.6% patients (representing 88.9% of
total samples) showed positive results with PCR. CONCLUSION: In testing urine of
legionellosis patients, it was suggested that three kits were all valuable tools
for diagnosis of legionellosis. Since over one-third of patients' serum samples
and most respiratory specimens showed positive results with PCR, the addition of
PCR for testing of these samples might be useful, particularly in cases of
culture negative and serum antibody negative patients.
PMID- 17033751
TI - Regional variation in outpatient antibiotic prescribing in Germany.
AB - OBJECTIVE: According to recent surveys, outpatient antibiotic prescribing in
Germany has been comparatively low among European countries. We assessed regional
variation in outpatient antibiotic use within Germany both for overall use as
well as for specific antibiotic drug classes. METHODS: Prescription data for the
year 2003 covering approximately 90% of the total population were analysed using
the ATC/WHO defined daily dose (DDD) methodology. Data were expressed in DDD per
1,000 persons covered by the insurance and day (DID). RESULTS: Outpatient
antibiotic prescribing in 2003 was 13.6 DID and ranged between 9.2 and 17.9 DID
in the different regions examined. Low consumption regions were eastern and
southern states. High consumption areas were in the west near the French and
Belgian border. This regional prescribing pattern was similar for children and
adults. Penicillins were the most frequent prescribed drugs, but their use
density showed a relatively large regional variation (factor 3.5), with
relatively low prescription frequency in the eastern states. In almost all
regions quinolones were used more often than trimethoprim-sulfamethoxazole.
CONCLUSION: The regional variation in recent outpatient antibiotic prescribing in
Germany is substantial. The relatively high antibiotic use in the western part of
the country is remarkable, remains unexplained and requires further study.
PMID- 17033752
TI - Is there significant regional variation in hospital antibiotic consumption in
Germany?
AB - OBJECTIVE: Outpatient antibiotic use in Germany differs substantially between
eastern and southern parts of the country (low use) and the western part (high
use). Whether similar regional variation exists in hospital antibiotic
consumption is not known. We investigated this issue using a convenience sample
of 145 hospitals providing data for the year 2003. METHODS: Data on hospital
consumption of systemic antibiotics in Anatomical Therapeutic Chemical (ATC)
class J01 were obtained from acute care hospitals that participated in an IMS
survey and had complete data (dispensed drugs and patient-days per year) for at
least one non-pediatric, non-psychiatric department or ward. A total of 275 non
ICU surgical departments/wards, 229 non-ICU non-surgical (general medicine,
haematology-oncology, neurology/stroke) departments/wards, and 184 ICUs were
analysed. Data were expressed in DDD (WHO/ATC definition version 2003) or daily
doses adapted for recommendations in hospitalized patients (RDD) per 100 patient
days (DDD/100 and RDD/100). FINDINGS: The weighted mean over all
departments/wards was 49.6 DDD/100 or 31.3 RDD/100, respectively. As expected,
ICU antibiotic use density was much higher than use in non-ICU areas, and use in
haematology-oncology was higher than in other non-surgical departments/wards. In
univariate analyses, region, hospital bed-size category, university affiliation
and haematology-oncology as specialty were associated with use density, but these
associations were only partly confirmed in multivariate logistic regression
analyses of factors associated with excess (> or = 75%) use density which showed
university affiliation and haematology-oncology but not hospital location to be
independently associated with comparatively high use. CONCLUSIONS: Antibiotic use
density in German acute care hospitals does not appear to differ significantly
between regions. Overall hospital consumption of antibiotics in this country
appears to be similar to what has been described from other parts of Europe. In
comparative analyses of hospital antibiotic consumption, data need to be adjusted
at least for university affiliation and haematology-oncology.
PMID- 17033753
TI - Epidemiology and clinical characteristics of patients with Staphylococcus
saprophyticus bacteriuria in Israel.
AB - BACKGROUND: Staphylococcus saprophyticus is a leading cause of lower urinary
tract infections (UTI) in young women in the USA, Canada and Scandinavian
countries, but seems to be very rare in other countries like Israel. The goal of
this study was to investigate the incidence of S. saprophyticus in Northern
Israel and to compare demographic and clinical characteristics of patients with
S. saprophyticus and Escherichia coli bacteriuria. PATIENTS AND METHODS: Data
from all patients with S. saprophyticus bacteriuria isolated in two major
laboratories in northern Israel during a 1-year period were analyzed and clinical
and epidemiological findings from 129 patients with S. saprophyticus bacteriuria
were compared to that of 129 patients with E. coli bacteriuria. RESULTS: The
incidence of S. saprophyticus in our region was 0.09% among all urine cultures
requested. Patients with S. saprophyticus bacteriuria are mainly young women,
more likely suffering asymptomatic bacteriuria, complain less of dysuria and
burning and are less hospitalized than those infected with E. coli. Reported risk
factors associated to S. saprophyticus bacteriuria such us seasonal variation,
occupation in meat products industry, use of contraceptives, or sexual activity
were not found by us. No nasal, vaginal, or rectal carriage was demonstrated.
CONCLUSION: S. saprophyticus is a very uncommon urinary pathogen in Northern
Israel. The natural reservoir of this uropathogen in our region remains unknown.
PMID- 17033754
TI - Severe reactivation of hepatitis B virus infection in a patient with hairy cell
leukemia: Should lamivudine prophylaxis be recommended to HBsAg-negative, anti
HBc-positive patients?
AB - The reverse seroconversion to hepatitis B virus infection has been sporadically
described in onco-haematological patients receiving cytotoxic therapy or
allogeneic bone marrow transplantation and can be associated with the development
of acute icteric hepatitis. We present a male HBsAg-negative, anti-HBc-positive
patient with Hairy Cell Leukemia who developed acute B hepatitis more than 1 year
after the last course of 2-CdA and 6 months after splenectomy, while the patient
was receiving therapy with alphaIFNr. The acute B hepatitis promptly responded to
lamivudine therapy followed by viral clearance.
PMID- 17033755
TI - Endogenous endophthalmitis with azole-resistant Candida albicans--Case report and
review of the literature.
AB - Candida endophthalmitis accounts for the majority of fungal endophthalmitis.
Despite its clinical relevance there are no controlled trials on different
treatment regimens. We report a case of endogenous endophthalmitis caused by
azole-resistant Candida albicans following abdominal surgery in an otherwise
healthy woman, and review the literature concerning treatment recommendations. In
consideration of the serious outcome with loss of sight in insufficiently treated
endophthalmitis we like to increase awareness to this disease entity and the
possibility of azole-resistance, even in treatment-naive patients.
PMID- 17033756
TI - Evidence of coinfection with distinct strains of Burkholderia multivorans in a
cystic fibrosis patient.
AB - We report a Cystic Fibrosis patient with chronic Burkholderia multivorans
infection involving persistency of one strain and temporary, consecutive
coinfection with two different strains. Comparison of the colony morphology with
the genotype revealed no correlation. These data are important for interpretation
of clinical outcome and transmission studies in CF patients.
PMID- 17033757
TI - Linezolid therapy of bloodborne teicoplanin-resistant Staphylococcus
haemolyticus.
PMID- 17033758
TI - Clinical news from the XVI International AIDS Conference: The attempt of a
summing up.
AB - Topics highlighted at the XVI International AIDS Conference in Toronto included
HIV/AIDS vaccine research, entry inhibitors, integrase inhibitors, new NNRTIs and
PIs, single-agent therapies, pre-exposure prophylaxis and microbicides. Beside
the large scientific part, policy and funding were of great concern. Within this
article we are trying to focus on topics with direct clinical relevance. This
includes new epidemiological and resistance data, results from current studies
investigating established and novel antiretroviral drugs and drug classes as well
as new findings in therapy management and strategies.
PMID- 17033759
TI - Is ACL reconstruction only for athletes? A study of the incidence of meniscal and
cartilage injuries in an ACL-deficient athlete and non-athlete population: an
Indian experience.
AB - While anterior cruciate ligament (ACL) reconstruction is readily offered to
athletes, non-athletes are often treated conservatively. We carried out a
retrospective, cross-sectional analysis study to compare the incidence of
meniscal and cartilage injuries in an athlete and non-athlete population in
relation to time of presentation since injury. The results were used to assess
the need and relevance of ACL reconstruction in the non-athlete population. The
study included 1375 patients who underwent ACL reconstruction between 1998 and
2004. These patients were initially broadly divided into two categories: athletes
(575) and non-athletes (800). Each category was then sub-divided into four
subgroups based on time elapsed between the injury and presentation at our clinic
(Group A, 3 months; Group B, 3-12 months; Group C, 1-3 years; Group D, more than
3 years). Arthroscopic findings were documented for medial and lateral meniscus
and cartilage injuries, and comparisons were made between the incidence of
associated injuries in the corresponding groups. There was a statistically
significant increase in the incidence of meniscal injuries and cartilage injuries
after 1 year in both the groups. There was no difference in the incidence of
meniscal and cartilage injuries in athletes and non-athletes among the
corresponding groups. (chi-square test, p = 0.05). These results demonstrate that
both athletes and non-athletes are equally susceptible for long-term meniscal and
cartilage injuries if ACL reconstruction is not carried out early.
PMID- 17033761
TI - Incidence of hip fracture in southeastern Norway: a study of 1,730 cervical and
trochanteric fractures.
AB - The incidence of hip fracture has been studied extensively, but there is still
some doubt whether the age-specific incidence is increasing. The proportion of
trochanteric fractures has varied and has also been said to be increasing. We
studied data on 1,730 prospectively registered cases from 1998-2003 and computed
age- and gender-specific incidence rates for intracapsular and trochanteric
fractures. The incidence of hip fracture for women over 50 years was 1,263 and
for men 452 per 100,000. The proportion of trochanteric fractures was 38% for
women and 41% for men. There was no significant difference in the proportion of
trochanteric fractures either between or within the genders, and the proportion
did not exceed 50% in any age group. These findings confirm the high incidence of
hip fracture in Norway but do not indicate any increase. The proportion of
trochanteric fractures also seems to be stable.
PMID- 17033762
TI - Evaluation of complications of three different types of proximal extra-articular
femur fractures: differences in complications, age, sex and surviving rates.
AB - The comparability of studies of extra-articular proximal femur fractures is
compromised by the lack of a widely accepted, simple classification system with
clinical and prognostic relevance. The aim of the study is to define the
complication profile as well as differences relating to age, gender and survival
rate of simple trochanteric fractures, intertrochanteric comminuted and
subtrochanteric fractures. Records of 335 consecutive patients were analysed.
Patients had a median follow-up of 10 (1-56) months, and were treated operatively
with three intramedullary nailing systems. Simple trochanteric fractures (n=67)
show wound healing problems (1.5%). Median age is m/f 77(45-98) years/ 85(39
101), and two-year survival rate is m/f 50.3%/ 84.9%. Intertrochanteric
comminuted fractures (n=204) show the highest complications (25%), 9.7%
femoralhead perforations, 3.5% hardware related problems and 11.8% wound healing
problems. Median age is m/f 75(41-94) years/ 85(54-100), survival rate is m/f
92.7%/ 66.5%. Complication rate is 17.0% in subtrochanteric fractures (n=64), no
femoralhead perforation but 9.1% other hardware problems and 7.8% wound healing
problems. Median age is m/f 72(24-91) years/ 83(38-99), survival rate is m/f
92.3%/ 67.9%. Females show higher complication rates compared to males (19%
versus 10%). The three types of fractures show different patterns of
complications, survival rates, age, and sex distribution.
PMID- 17033763
TI - Are drains required following a routine primary total joint arthroplasty?
AB - The purpose of this study was to evaluate the benefits of suction drainage
following primary total joint arthroplasty. We reviewed primary total hip and
knee replacements separately and together in 126 consecutive patients. There were
63 patients each in the drainage and no drainage groups. Sex distribution and
anticoagulant use were similar in the two groups. All patients underwent the same
operative technique and method of closure. The mean postoperative fall in
haemoglobin was 3.2 and 3.3 gm/dl in the drainage and no drainage groups
respectively. There was no statistically significant difference between the two
groups with regard to blood transfusion requirements, rehabilitation time,
postoperative complications such as hypotension and wound infections (p>0.05).
The average rehabilitation time in both groups was 8-9 days. The routine use of a
suction drain is unnecessary after an uncomplicated total joint arthroplasty.
PMID- 17033764
TI - Surgical treatment of undisplaced femoral neck fractures in the elderly.
AB - The study was a retrospective evaluation and comparison. Eighty-four elderly
patients (> 60 years) with undisplaced intracapsular femoral neck fractures were
treated with osteosynthesis with either dynamic hip screws (DHS) or multiple
cannulated screws (MCS). The Singh index was used to evaluate bone quality. All
patients were followed up retrospectively for at least 12 months. The clinical
results were compared between the DHS and MCS groups. Both groups were similar in
respect of injury mechanisms, mean Singh index, injury-surgery interval, gender
and age (all p values > or = 0.29). The MCS group had significantly smaller wound
incisions, less haemoglobin level drops, lower blood transfusion rates and
shorter hospital stays than the DHS group (all p values < or = 0.008). However,
the DHS group had a higher rate of overall success when compared to the MCS group
(97.5% versus 84.1%, p=0.04). In conclusion, although DHS fixation requires a
larger skin incision and more soft tissue dissection, its use in elderly patients
with osteoporosis is recommended due to simple, efficacy and high overall success
rate.
PMID- 17033765
TI - Minimally invasive plate osteosynthesis in the treatment of proximal humeral
fracture.
AB - The management of fractures of the proximal shaft of the humerus has been
evolving since the development of new techniques and new implants in recent
years. It seems that this kind of fracture has an increasing incidence in the
older, osteoporotic population. In the last 2 years, we have operated on 17
patients, with an average age of 65, who had proximal humeral shaft fractures
treated by minimally invasive percutaneous osteosynthesis (MIPO) technique using
the metaphyseal locking compression plate. Our study evaluated the surgical
technique used and the outcome for these patients with regards to their range of
movement and shoulder function. Our results showed that all the patients could
achieve at least 140 masculine of shoulder abduction in the first 6 months after
the operation, except for three patients who had shoulder impingement. These
patients had an average Constant score of 76.8. All fractures had bony union at 6
months, except one, which was probably due to poor reduction in the initial
operation. Another complication that we encountered was radial nerve neuropraxia.
The ways to prevent these complications are discussed. In conclusion, MIPO
fixation using the metaphyseal locking compression plate is a good option for the
management of proximal humeral shaft fractures. It provides early functional
recovery, but we had to pay special attention to some of the surgical details in
order to minimise complications.
PMID- 17033766
TI - Tension-band wiring of transverse fractures of patella. The effect of site of
wire twists and orientation of stainless steel wire loop: a biomechanical
investigation.
AB - Tension-band wiring is commonly used to treat transverse patella fractures. The
most common configuration has parallel Kirschner (K) wires and a stainless steel
wire loop placed in a vertically oriented figure of eight. Early mobilisation is
important but can cause detrimental displacement at the fracture site. A wooden
model of a transversely fractured patella was used to compare different fixation
constructs. The fracture was fixed using two K wires and a stainless steel wire
loop. One or two wire twists were used, placed either arbitrarily or at corners
of the loop. The loop was oriented either vertically or horizontally.
Interfragmentary compression at the point of wire breakage and permanent
displacement on cyclic loading was measured for each construct. Placement of the
figure of eight in a horizontal orientation with two wire twists at the corner
improved interfragmentary compression by 63% (p<0.05, Tukey post hoc test). On
cyclic loading, all constructs with vertical figure of eight but none with a
horizontal construct failed (p=0.01; Fisher's exact test). Permanent fracture
displacement after cyclic loading was 67% lower with horizontal figure of eight
constructs (p<0.05; t test). Placing wire twists at the corner and a horizontal
placement of figure of eight improves stability of the construct.
PMID- 17033768
TI - Near-infrared reflectance spectroscopy as a fast and non-destructive tool to
predict foliar organic constituents of several woody species.
AB - Near-infrared reflectance spectroscopy (NIRS) was used to estimate N, neutral
detergent fibre (NDF), acid detergent fibre (ADF), lignin and cellulose contents
in leaves of a heterogeneous group of 17 woody species from the Central Western
region of the Iberian Peninsula. The sample set consisted of 182 samples of
leaves of deciduous and evergreen species, showing a wide range of concentrations
determined by reference methods: 6.60-35.2 g kg-1 (N), 15.5-66.0% (NDF), 10.2
57.3% (ADF), 3.45-27.4% (lignin) and 5.79-31.3% (cellulose). Reflectance spectra,
obtained for samples of dried and ground leaves, were recorded as log1/R
(R=reflectance) from 1,100 to 2,500 nm. NIRS calibrations were developed using
multiple linear (MLR) and partial least-squares (PLSR) regressions, and tested by
external validation. Spectral data were transformed to the first and second
derivative (1D, 2D). The PLSR method and derivative transformations provided the
best statistics and showed lower standard errors of calibration (SEC) and higher
coefficients of multiple determination (R2). In the external validation the
standard errors of prediction (SEP) were 0.76 g kg-1 (N), 2.11% (NDF), 1.47%
(ADF), 0.85% (lignin) and 0.86% (cellulose). The results obtained show that NIRS
is very effective for the estimation of these organic constituents in leaf tissue
of woody species. This technique can be used in ecological or ecophysiological
studies as an alternative to the more time-consuming standard methods.
PMID- 17033769
TI - Tagging of avidin immobilized beads with biotinylated YAG:Ce3+ nanocrystal
phosphor.
AB - YAG:Ce3+ nanoparticles 9.5+/-1.2 nm in diameter have been synthesized from
aluminium isopropoxide and acetates of yttrium and cerium in 1,4-butanediol (1,4
BD) by autoclave treatment at 300 degrees C for 2 h. After replacing 1,4-BD by
ultrapure water, NH2 groups were introduced on the surface of YAG:Ce3+
nanoparticles by addition of 3-aminopropyltrimethoxysilane then biotinylation
with sulfo-NHS-LC-biotin. We demonstrated that avidin immobilized beads are
tagged by biotinylated YAG:Ce3+ nanoparticles by the selective avidin-biotin
interaction, furnishing a green fluorescent image on excitation with blue light.
This result indicates that YAG:Ce3+ nanoparticle phosphors have much potential in
biological applications.
PMID- 17033770
TI - Characterization of the coupling of quantum dots and immunoglobulin antibodies.
AB - Water-soluble quantum dots (QDs) were used to label goat anti-human
immunoglobulin antibodies (Abs), and the labeling process was characterized by
column purification. The QDs obtained in organic solvent were modified with
mercaptoacetic acid (MAA) and became water-soluble. These water-soluble QDs were
linked to the antibodies using the coupling reagents ethyl-3-(dimethyl
aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The linking
process was shown to be effective by ultra-filter centrifugation and column
purification. After comparing the quantities of Abs and water-soluble QDs
involved in the linking reaction via column purification, it was found that a
molar Abs:QD ratio of >1.2 resulted in most of the water-soluble QDs becoming
covalently linked to the Abs. The circular dichroism (CD) spectra of Abs and QD
Ab conjugates were very similar to each other, indicating that the secondary
structure of Abs remained largely intact after the conjugation. Finally, antigen
(Ag)-antibody (Ab) recognition reactions perfomed on the surface of a glass slide
showed that the conjugate retained the activity of Abs. This work lends support
to the idea of linking biomolecules to QDs, and thus should aid the application
of QDs to the life sciences.
PMID- 17033771
TI - Labeling the human skeleton with 41Ca to assess changes in bone calcium
metabolism.
AB - Bone research is limited by the methods available for detecting changes in bone
metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical
markers are subject to significant intra-individual variation. In the study
presented here, we evaluated the isotopic labeling of bone using 41Ca, a long
lived radiotracer, as an alternative approach. After successful labeling of the
skeleton, changes in the systematics of urinary 41Ca excretion are expected to
directly reflect changes in bone Ca metabolism. A minute amount of 41Ca (100 nCi)
was administered orally to 22 postmenopausal women. Kinetics of tracer excretion
were assessed by monitoring changes in urinary 41Ca/40Ca isotope ratios up to 700
days post-dosing using accelerator mass spectrometry and resonance ionization
mass spectrometry. Isotopic labeling of the skeleton was evaluated by two
different approaches: (i) urinary 41Ca data were fitted to an established
function consisting of an exponential term and a power law term for each
individual; (ii) 41Ca data were analyzed by population pharmacokinetic (NONMEM)
analysis to identify a compartmental model that describes urinary 41Ca tracer
kinetics. A linear three-compartment model with a central compartment and two
sequential peripheral compartments was found to best fit the 41Ca data. Fits
based on the use of the combined exponential/power law function describing
urinary tracer excretion showed substantially higher deviations between predicted
and measured values than fits based on the compartmental modeling approach. By
establishing the urinary 41Ca excretion pattern using data points up to day 500
and extrapolating these curves up to day 700, it was found that the calculated
41Ca/40Ca isotope ratios in urine were significantly lower than the observed
41Ca/40Ca isotope ratios for both techniques. Compartmental analysis can overcome
this limitation. By identifying relative changes in transfer rates between
compartments in response to an intervention, inaccuracies in the underlying model
cancel out. Changes in tracer distribution between compartments were modeled
based on identified kinetic parameters. While changes in bone formation and
resorption can, in principle, be assessed by monitoring urinary 41Ca excretion
over the first few weeks post-dosing, assessment of an intervention effect is
more reliable approximately 150 days post-dosing when excreted tracer originates
mainly from bone.
PMID- 17033772
TI - Single-molecule tracking in eukaryotic cell nuclei.
PMID- 17033773
TI - A screening system for active and enantioselective amidase based on its acyl
transfer activity.
AB - A novel enantioselective amidase screening system was developed and proved to be
efficient and accurate. This screening system employed acyl transfer activity of
amidase in the presence of hydroxylamine, leading to the formation of hydroxamic
acids, followed by spectrophotometric quantification of hydroxamic acid/iron(III)
complexes. The enantioselectivities of amidase were evaluated by employing (R, S)
2, 2-dimethyl cyclopropanecarboxamide (1), (S)-2, 2-dimethyl
cyclopropanecarboxamide and their mixture as substrates concurrently under the
same conditions. To prove the accuracy of the screening system,
enantioselectivity of acyl transfer reaction (E (T)) and that of hydrolytic
reaction (E (H)) was compared. With this method, we obtained eight microorganism
strains with enantioselective amidase from 523 isolates, two of which showed R
stereospecific avtivity for (R, S)-1.
PMID- 17033774
TI - Early attack and subsequent changes produced in an industrial lignin by a fungal
laccase and a laccase-mediator system: an analytical approach.
AB - An industrial kraft pine lignin (Indulin AT, KL) was characterized and treated in
both aqueous-buffered media and dioxane to water, either with a partially
purified laccase from Fusarium proliferatum or with the laccase plus 2,2'-azino
bis-3-ethylbenzothiazoline-6-sulfonic-acid (ABTS) as mediator. The changes in the
lignin after different incubation periods were analyzed through the application
of high performance liquid chromatography (HPLC), UV-visible (Vis) spectroscopy
and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). At the onset of
incubation, laccase-treated samples showed a slight polymerization and strong
modifications in UV-Vis spectra. Through Py-GC/MS, a decrease in phenolic and
methoxy-bearing pyrolysis products was observed, in contrast to an increase in
the more oxidized products. After longer incubation periods (48 h) a substantial
polymerization was detected by HPLC, along with a decrease in the guaiacyl (G)
units. In contrast, the analysis by HPLC of the samples recovered from the
laccase-ABTS system (LMS) showed an intense depolymerization, accompanied by a
sizeable loss in G units and a decrease in the methyl and ethyl side-chain
phenolic compounds. These results provide conclusive evidence of a rapid initial
attack of the industrial lignin by laccase and notable modifications in the KL
after longer incubation periods with laccase or LMS.
PMID- 17033775
TI - Outdoor cultivation of lutein-rich cells of Muriellopsis sp. in open ponds.
AB - The growth performance of the chlorophycean microalga Muriellopsis sp. outdoors
in open tanks agitated with a paddlewheel and its ability to accumulate
carotenoids have been evaluated throughout the year. The cells grown in the open
system had free lutein as the main carotenoid, with violaxanthin, beta-carotene,
and neoxanthin also present. Lutein content of the dry biomass ranged from 0.4 to
0.6%, depending on the growth and environmental conditions. In addition, the
biomass of Muriellopsis sp. had a high content in both protein and lipids with
about half of the fatty acids being of the polyunsaturated type, with alpha
linolenic acid accounting for almost 30% of the total fatty acids. The effect of
determinant parameters on the performance of the cultures in open tanks was
evaluated. Operating conditions that allow the maintenance of productive cultures
were established under semicontinuous regime for 9 months throughout the year.
Biomass and lutein yields in the open system were not far from those in closed
tubular photobioreactors, and reached productivity values of 20 g dry biomass,
containing around 100 mg lutein m(-2) day(-1) in summer. The outdoor culture of
Muriellopsis sp. in open ponds thus represents a real alternative to established
systems for the production of lutein.
PMID- 17033776
TI - [Rational minimally invasive treatment of pAOD: when should a conservative
approach, PTA, or stent be chosen?].
AB - In order to obtain optimal results and satisfied patients, rational therapy of
pAOD should strictly follow national and international society guidelines. In
particular cases an individual therapeutic concept seems justified beyond these
guidelines. Based on clinical data and driven by costs, aortic and iliac lesions
may be treated by PTA or selective stent placement with equal results; however,
long-term data justify also primary, direct stenting. For treatment of
infrainguinal and popliteal stenotic lesions primary stenting should be
restricted to PTA failure (dissection, recoil, occlusion); except for treatment
of extended lesions, primary stenting compared to PTA alone seems beneficial in
terms of midterm patency. Endovascular procedures below the knee and at the toe
should be limited to existing limb-threatening ischemia in order to save the
extremity; whether PTA or stenting is advantageous has not yet determined.
PMID- 17033777
TI - Solid-state NMR characterization of the putative membrane anchor of TWD1 from
Arabidopsis thaliana.
AB - Structure and membrane interaction of a 31 amino acid residue fragment of the
membrane bound FKBP-like protein twisted dwarf 1 (TWD1) from Arabidopsis thaliana
was investigated by solid-state NMR spectroscopy. The studied peptide TWD1(335
365) contained the putative membrane anchor of the protein (residues 339-357)
that was previously predicted by sequence hydrophobicity analysis. The TWD1
peptide was synthesized by standard solid phase peptide synthesis and contained
three uniformly (13)C- and (15)N-labelled residues (Phe 340, Val 350, Ala 364).
The peptide was incorporated into either multilamellar vesicles or oriented
planar membranes composed of an equimolar ternary phospholipid mixture (POPC,
POPE, POPG), where the POPC was sn-1 chain-deuterated. (31)P NMR spectra of the
membrane in the absence and in the presence of the peptide showed axially
symmetric powder patterns indicative of a lamellar bilayer phase. Further, the
addition of peptide caused a decrease in the lipid hydrocarbon chain order as
indicated by reduced quadrupolar splittings in the (2)H NMR spectra of the POPC
in the membrane. The conformation of TWD1(335-365) was investigated by (13)C
cross-polarization magic-angle spinning NMR spectroscopy. At a temperature of -30
degrees C all peptide signals were resolved and could be fully assigned in two
dimensional proton-driven (13)C spin diffusion and (13)C single quantum/double
quantum correlation experiments. The isotropic chemical shift values for Phe 340
and Val 350 exhibited the signature of a regular alpha-helix. Chemical shifts
typical for a random coil conformation were observed for Ala 364 located close to
the C-terminus of the peptide. Static (15)N NMR spectra of TWD1(335-365) in
mechanically aligned lipid bilayers demonstrated that the helical segment of
TWD1(335-365) adopts an orientation perpendicular to the membrane normal. At 30
degrees C, the peptide undergoes intermediate time scale motions.
PMID- 17033779
TI - [New study results in cardiology].
PMID- 17033778
TI - Spectrally resolved time-correlated single photon counting: a novel approach for
characterization of endogenous fluorescence in isolated cardiac myocytes.
AB - A new setup for time-resolved fluorescence micro-spectroscopy of cells, based on
multi-dimensional time-correlated single photon counting, was designed and
tested. Here we demonstrate that the spectrometer allows fast and reproducible
measurements of endogenous flavin fluorescence measured directly in living
cardiac cells after excitation with visible picosecond laser diodes. Two
complementary approaches for the analysis of spectrally- and time-resolved
autofluorescence data are presented, comprising the fluorescence decay fitting by
exponential series and the time-resolved emission spectroscopy analysis. In
isolated cardiac myocytes, we observed three distinct lifetime pools with
characteristic lifetime values spanning from picosecond to nanosecond range and
the time-dependent red shift of the autofluorescence emission spectra. We
compared obtained results to in vitro recordings of free flavin adenine
dinucleotide (FAD) and FAD in lipoamide dehydrogenase (LipDH). The developed
setup combines the strength of both spectral and fluorescence lifetime analysis
and provides a solid base for the study of complex systems with intrinsic
fluorescence, such as identification of the individual flavinoprotein components
in living cardiac cells. This approach therefore constitutes an important
instrumental advancement towards redox fluorimetry of living cardiomyocytes, with
the perspective of its applications in the investigation of oxidative metabolic
state under pathophysiological conditions, such as ischemia and/or metabolic
disorders.
PMID- 17033780
TI - [Hypercalcemia in dialysis-dependent renal insufficiency].
PMID- 17033781
TI - [Treatment of pituitary gland hyperfunction: from acromegaly to prolactinoma].
AB - Evidence based drug therapy is currently available for the treatment of
prolactinomas and growth hormone secreting adenomas (acromegaly). Dopamine
agonists such as bromocriptine, quinagolide or cabergoline represent the standard
therapy for the treatment of micro- and macro-prolaktinomas. In pregnancy, more
differentiated, individual and patient-adapted therapeutic procedures have to be
considered. Transsphenoidal adenomectomy is the treatment of choice for patients
suffering from acromegaly. If biochemical cure (defined by normalized IGF-1 serum
levels or by a GH nadir <1 microg/l during a 3-h oral glucose tolerance test)
cannot be achieved, somatostatin analogues such as octreotide and lanreotide are
effective. In some cases, dopamine agonists can be added. In therapy-resistant
cases, growth hormone receptor antagonists can be used.
PMID- 17033782
TI - [Water and electrolyte disturbances in critical care].
AB - Management of critically ill patients regularly involves the treatment of water
and electrolyte disturbances. Moreover, critical care itself may contribute to
volume overload and electrolyte abnormalities. Initial therapy should be followed
by consequent diagnostic evaluation. The shift of volume and potassium in severe
pancreatitis, for example, may lead to a life-threatening situation. In brain
dead patients, successful organ donation is facilitated by careful maintenance of
water and electrolyte homeostasis.
PMID- 17033783
TI - Monte Carlo simulation of intercalated carbon nanotubes.
AB - Monte Carlo simulations of the single- and double-walled carbon nanotubes (CNT)
intercalated with different metals have been carried out. The interrelation
between the length of a CNT, the number and type of metal atoms has also been
established. This research is aimed at studying intercalated systems based on
CNTs and d-metals such as Fe and Co. Factors influencing the stability of these
composites have been determined theoretically by the Monte Carlo method with the
Tersoff potential. The modeling of CNTs intercalated with metals by the Monte
Carlo method has proved that there is a correlation between the length of a CNT
and the number of endo-atoms of specific type. Thus, in the case of a metallic
CNT (9,0) with length 17 bands (3.60 nm), in contrast to Co atoms, Fe atoms are
extruded out of the CNT if the number of atoms in the CNT is not less than eight.
Thus, this paper shows that a CNT of a certain size can be intercalated with no
more than eight Fe atoms. The systems investigated are stabilized by coordination
of 3d-atoms close to the CNT wall with a radius-vector of (0.18-0.20) nm. Another
characteristic feature is that, within the temperature range of (400-700) K,
small systems exhibit ground-state stabilization which is not characteristic of
the higher ones. The behavior of Fe and Co endo-atoms between the walls of a
double-walled carbon nanotube (DW CNT) is explained by a dominating van der Waals
interaction between the Co atoms themselves, which is not true for the Fe atoms.
PMID- 17033784
TI - Precursor-directed biosynthesis of 6-deoxyerythronolide B analogues is improved
by removal of the initial catalytic sites of the polyketide synthase.
AB - Precursor-directed biosynthesis has been shown to be a powerful tool for the
production of polyketide analogues that would be difficult or cost prohibitive to
produce from medicinal chemistry efforts alone. It has been most extensively
demonstrated using a KS1 null mutation (KS1(0)) to block the first round of
condensation in the biosynthesis of the erythromycin polyketide synthase (DEBS)
for the production of analogues of its aglycone, 6-deoxyerythronolide B (6-dEB).
Here we show that removing the DEBS loading domain and first module (mod1Delta),
rather than using the KS1(0) system, can lead to an increase in the utilization
of some chemical precursors and production of 6-dEB analogues (R-6dEB) in both
Streptomyces coelicolor and Saccharopolyspora erythraea. While the difference in
utilization of the precursor was diketide specific, in strains fed (2R*, 3S*)-5
fluoro-3-hydroxy-2-methylpentanoate N-propionylcysteamine thioester, twofold
increases in both utilization of the diketide and 15-fluoro-6dEB (15F-6dEB)
production were observed in S. coelicolor, and S. erythraea exhibited a tenfold
increase in production of 15-fluoro-erythromycin when utilizing the mod1Delta
rather than the KS1(0) system.
PMID- 17033785
TI - A comparative linkage map of oilseed rape and its use for QTL analysis of seed
oil and erucic acid content.
AB - We have developed a new DH mapping population for oilseed rape, named TNDH, using
genetically and phenotypically diverse parental lines. We used the population in
the construction of a high stringency genetic linkage map, consisting of 277
loci, for use in quantitative genetic analysis. A proportion of the markers had
been used previously in the construction of linkage maps for Brassica species,
thus permitting the alignment of maps. The map includes 68 newly developed
Sequence Tagged Site (STS) markers targeted to the homologues of defined genes of
A. thaliana. The use of these markers permits the alignment of our linkage map
with the A. thaliana genome sequence. An additional 74 loci (31 newly developed
STS markers and 43 loci defined by SSR and RFLP markers that had previously been
used in published linkage maps) were added to the map. These markers increased
the resolution of alignment of the newly constructed linkage map with existing
Brassica linkage maps and the A. thaliana genome sequence. We conducted field
trials with the TNDH population at two sites, and over 2 years, and identified
reproducible QTL for seed oil content and erucic acid content. The results
provide new insights into the genetic control of seed oil and erucic acid content
in oilseed rape, and demonstrate the utility of the linkage map and population.
PMID- 17033786
TI - Diversity arrays technology (DArT) for high-throughput profiling of the hexaploid
wheat genome.
AB - Despite a substantial investment in the development of panels of single
nucleotide polymorphism (SNP) markers, the simple sequence repeat (SSR)
technology with a limited multiplexing capability remains a standard, even for
applications requiring whole-genome information. Diversity arrays technology
(DArT) types hundreds to thousands of genomic loci in parallel, as previously
demonstrated in a number diploid plant species. Here we show that DArT performs
similarly well for the hexaploid genome of bread wheat (Triticum aestivum L.).
The methodology previously used to generate DArT fingerprints of barley also
generated a large number of high-quality markers in wheat (99.8% allele-calling
concordance and approximately 95% call rate). The genetic relationships among
bread wheat cultivars revealed by DArT coincided with knowledge generated with
other methods, and even closely related cultivars could be distinguished. To
verify the Mendelian behaviour of DArT markers, we typed a set of 90 Cranbrook x
Halberd doubled haploid lines for which a framework (FW) map comprising a total
of 339 SSR, restriction fragment length polymorphism (RFLP) and amplified
fragment length polymorphism (AFLP) markers was available. We added an equal
number of DArT markers to this data set and also incorporated 71 sequence tagged
microsatellite (STM) markers. A comparison of logarithm of the odds (LOD) scores,
call rates and the degree of genome coverage indicated that the quality and
information content of the DArT data set was comparable to that of the combined
SSR/RFLP/AFLP data set of the FW map.
PMID- 17033787
TI - [Hyperplastic scars and keloids: part II: Surgical and non-surgical treatment
modalities].
AB - Aberrant wound healing results in unsightly scarring, hypertrophic scarring, and
keloid formation, causing functional and cosmetic deformities, discomfort,
psychological stress, and patient dissatisfaction. Scar management, both surgical
and non-surgical, continue to be important issues for the facial plastic surgeon.
Many techniques for the management of hypertrophic scars and keloids have been
proven through extensive use, but few are supported by prospective studies with
adequate control groups. Several new therapies showed good results in small-scale
trials, but these have not been repeated in larger trials with long-term follow
up. This article presents an overview of the available therapies and provides
recommendations for the treatment of abnormal scarring. The recommendations focus
on the management of hypertrophic scars and keloids. Strategies for the
management of keloids and hypertrophic scars are of continuing interest and
studies are necessary to understand the basic mechanisms causing aberrant wound
healing. In addition, an overview of new developments in molecular wound
management and gene therapy, as they relate to facial plastic surgery, is
provided.
PMID- 17033788
TI - Mycoplasma hominis osteitis in an immunocompetent man.
AB - Mycoplasma hominis has been associated with pelvic inflammatory illness,
postpartum and neonatal infections and respiratory tract diseases. It is rarely
isolated from patients with other infections. Reported here is a case of tibial
osteitis that occurred in a 16-year-old immunocompetent man. Clinical and
laboratory findings improved under treatment with clindamycin and
fluoroquinolones.
PMID- 17033789
TI - Prevalence of Borrelia burgdorferi s.l. and Anaplasma phagocytophilum in the wood
tick Ixodes ricinus in the Province of Trento, Italy.
PMID- 17033790
TI - Catheter-associated fungemia due to Exophiala oligosperma in a leukemic child and
review of fungemia cases caused by Exophiala species.
AB - A case of catheter-associated fungemia due to Exophiala oligosperma in a 3-year
old leukemic child is presented. The etiologic agent was isolated from blood
specimens and the catheter tip. The isolate was identified by its morphological
characteristics and DNA sequencing of the internal transcribed spacer region of
rDNA. Despite initial amphotericin B and itraconazole therapy, the child's fever
subsided only after removal of the catheter. A review of the medical literature
revealed 29 cases of infection due to Exophiala species. Twenty-three of these 29
patients had a CVC in place when they developed fever or other manifestations of
fungemia. Withdrawal of the CVC together with amphotericin B and/or itraconazole
therapy generally resulted in a good prognosis.
PMID- 17033792
TI - Metabolic response during intermittent graded sprint running in moderate
hypobaric hypoxia in competitive middle-distance runners.
AB - The purpose of this study was to determine whether the metabolic response and
running performance during intermittent graded sprint running were affected by
moderate hypobaric hypoxia (H; 2,500 m above sea level) in competitive middle
distance runners. Nine male runners performed intermittent graded sprint running
until exhaustion, to evaluate the metabolic response and running performance in H
and normobaric normoxia (N). The test constructed of incremental (25 m min(-1))
20 s running bouts (4 degrees inclination) interspaced with 100 s recovery
periods. Maximal running speed was not different between conditions [453 (7) m
min(-1) vs. 458 (4) m min(-1) in N vs. H]. V(O2) at each speed was lower in H
than N (ANOVA; P < 0.05). Although, oxygen deficit (D(O2)) at each speed was not
different between N and H (ANOVA; P = 0.1), total accumulated D(O2) in all bouts
was significantly higher in H than N [165 (10) ml kg(-1) in N and 173 (10) ml kg(
1) in H]. The ratio of D(O2).V(O2)(-1) was similar in all bouts, but higher in H
than N. These results suggest that intermittent graded sprint running performance
is not affected by moderate hypobaria despite a reduction in the energy supplied
by aerobic metabolism due to a compensatory increase in the energy supplied by
the anaerobic metabolism in competitive middle-distance runners.
PMID- 17033791
TI - Effect of gravity in long-term vitreous tamponade: in vivo investigation using
perfluorocarbon liquids and semi-fluorinated alkanes.
AB - PURPOSE: In order to investigate whether gravity is the reason for retinal
degeneration in long-term vitreous tamponade, perfluorohexyloctane (F6H8),
perfluorodecalin (PFD), and a mixture of F6H8/PFD were compared. MATERIALS AND
METHODS: Each group of 5 rabbits received a 3-month tamponade with either PFD
(pure) (1.93 g/cm(3)), F6H8 (pure) (1.33 g/cm(3)), or a 1:1 mixture of F6H8/PFD
(1.62 g/cm(3)). Electroretinograms (ERG) were performed pre- and postoperatively.
Lower and upper retinal areas were compared using immunohistochemical methods.
Transmission electron microscopy was performed to investigate alterations in the
photoreceptors. RESULTS: All three substances were tolerated well in rabbit eyes
for up to 3 months. Dispersion was seen earliest with PFD and latest with pure
F6H8. None of the substances demonstrated inflammatory reactions or vascular
alterations. ERGs were not considerably altered with any of the substances.
Histology of the retina showed alterations in the cell counts within the inner
and outer nuclear layer that were not attributable to the gravity of the
tamponading agent. CONCLUSION: In contrast to previously published work, this
study did not detect any tamponade-related structural damage of the retina after
a 3-months tamponade in the rabbit model. Based upon this study, we conclude that
gravity might not be causally linked to retinal damage.
PMID- 17033794
TI - [Left hemifacial flushing and sweating].
PMID- 17033793
TI - Effects of two types of inactivity on the number of white blood cells in rats.
AB - Prolonged inactivity is known to induce changes in responses of many
physiological defense systems such as the hypothalamo-hypophyseal-adrenocortical
axis, the sympathetic nervous system, and immuno-responsive systems. However,
effects of various types of inactivity on immuno-responsive systems are still
unknown. Therefore, the effects of two types of inactivity (immobilization: IMM
and whole body suspension: WBS) on the number of white blood cells were studied
in rats. Rats were divided into the control group and each inactivity group to
compare the number of total white blood cells, lymphocytes, monocyte, neutrophil,
eosinophil, and basophil during the experimental periods. Both IMM and WBS were
maintained for 11 days. IMM markedly increased the number of total white blood
cells, monocyte, neutrophil, and eosinophil in the 1st to 10th day. However, the
number of total white blood cells, monocyte, neutrophil, and eosinophil during
the experiment of WBS were characterized by the presence of a lag phase followed
by the significant increased actions. IMM did not change the number of basophil
during the experimental period. However, WBS increased the number of basophil in
the 1st to 8th day to 2.8-4.8 times, compared with the values of the control.
Both IMM and WBS did not change the number of lymphocytes. From these results,
WBS increases the number of natural immunity cells without changing acquired
immunity cells, and there are different responses in the number of total white
blood cells, monocyte, neutrophil, eosinophil, and basophil between IMM and WBS.
PMID- 17033795
TI - The radiologist assistant: the solution to radiology workforce needs.
AB - Since 2003 the radiologist assistant (RA) was introduced in response to the
severe shortage of radiologists and the increased demand for medical imaging
services. Other non-physician clinicians, such as PAs, currently play an
important role in the medical imaging environment. The article discusses the
reasons physician assistants have found favor with interventional radiologists,
and advocates an increased role for physician extenders in Radiology. It refutes
the skeptics who question whether the new profession will alleviate the manpower
crisis in Radiology. The authors suggest that RAs are the ideal complement to
radiologists; and based on their radiologic technology background, have a vested
interest in the field.
PMID- 17033797
TI - The grey zone between pure (neuro)endocrine and non-(neuro)endocrine tumours: a
comment on concepts and classification of mixed exocrine-endocrine neoplasms.
AB - Terms such as "mixed endocrine-exocrine carcinoma" (MEEC) and "adenocarcinoma
with neuroendocrine (NE) differentiation" (ADC-NE) identify tumours belonging to
the spectrum of neoplasms with divergent exocrine and (neuro)endocrine
differentiation. These tumours display variable quantitative extent of the two
components, potentially ranging from 1 to 99%, and variable structural patterns,
ranging from single scattered NE cells to a well-defined NE tumour cell
population organized in organoid, trabecular or solid growth patterns. In the
present report, the grey zone of tumours/carcinomas with mixed NE and non-NE
features is explored for various organs. From a practical point of view, MEECs
differ from carcinomas with focal NE differentiation by (1) the extension of each
component (more than 30%) and (2) the structural pattern of the NE component,
either organoid for well-differentiated or solid/diffuse for poorly
differentiated cases. In MEECs, the most aggressive cell population drives the
clinical behaviour. Conversely, ADC-NE generally do not show a different clinical
outcome, compared to the corresponding conventional forms, except for prostatic
adenocarcinoma, in which NE cells are a negative prognostic factor. The
recognition of MEECs may be of relevance for a targeted therapeutic strategy,
foreseeing the use of biotherapies similar to those proposed for pure NE tumours.
PMID- 17033796
TI - Disease modifying genes in cystic fibrosis: therapeutic option or one-way road?
AB - Cystic fibrosis (CF) is the most common genetic disease among Caucasians and is
caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF
affects multiple organs but lung disease is the major determinant for morbidity
and mortality. Many studies have focussed on the correlation between CFTR
genotype and severity of disease. Since patients with identical CFTR mutations
often show considerable variability in disease progression, genes other than CFTR
are thought to have the potential to modify the course of lung disease in CF
patients. Therefore, identification of CF-modifying genes has become the goal of
several studies over the last 15 years. Pharmaceutical approaches for CF lung
disease have been developed regardless of the underlying genetic defect and in
general target symptoms such as airway obstruction and treatment of bacterial
infection. Analysing the pathophysiological processes of modifiers may lead to
the discovery of pathways involved in CF pathophysiology and possibly to the
design of new therapeutics. The purpose of this review is not only to list
potential CFTR modifier genes, but also to discuss new therapeutic strategies
that could be derived from knowledge of these CF modifiers.
PMID- 17033798
TI - Expression of Epstein-Barr virus (EBV)-encoded latent membrane proteins and STAT3
activation in nasopharyngeal carcinoma.
AB - The Epstein-Barr virus (EBV) is associated with virtually all cases of
undifferentiated nasopharyngeal carcinoma (NPC), and it was proposed that the EBV
encoded transforming protein, latent membrane protein (LMP) 1, may play a role in
the neoplastic process. It was proposed recently that LMP1 expression in
epithelial cells may be regulated through a loop involving activated signal
transducer and activator of transcription 3 (STAT3), LMP1, LMP1-mediated
induction of interleukin (IL)-6 expression and STAT3 activation through the IL-6
receptor. This autoregulatory loop may be suppressed by another viral protein,
LMP2A, an effect which in turn can be overcome by exogenous IL-6. Here we show
that, as expected, expression of LMP1 and LMP2A tend to be exclusive in NPC
tumours. Rare cases showing a co-expression of both proteins can be explained by
STAT3 activation via the receptors for IL-6 or epidermal growth factor. STAT3
activation was a consistent feature of NPC tumour cells. However, in most cases,
this was not accompanied by detectable expression of LMP1, suggesting either that
LMP2A expression may suffice to suppress LMP1 expression or that additional
factors may be operational. This study emphasises the need to correlate in vitro
results with observational studies of ex vivo tumour tissues.
PMID- 17033799
TI - Intrahepatic sarcomatoid cholangiocarcinoma of round cell variant: a case report
and immunohistochemical studies.
AB - Sarcomatoid transformation was observed in 4.5% of autopsied cases of
intrahepatic cholangiocarcinoma. Here, we report a case of intrahepatic
sarcomatoid cholangiocarcinoma with round cell feature, extremely rare variant.
An 87-year-old man was incidentally found to have a tumor in the left lobe of the
liver by abdominal computed tomography scans. The patient was clinically
diagnosed to have intrahepatic cholangiocarcinoma and received palliative care
without specific treatment. He died of hepatic insufficiency 3 months after the
diagnosis. The autopsied liver specimens showed a reddish gray tumor of 4.0x2.8
cm in size. Histologically, the tumor was centrally hemorrhagic and necrotic and
was composed of tubular adenocarcinoma and a round cell component, which has an
eccentrically located nucleus and eosinophilic cytoplasm without mucin
production. Immunohistochemically, the adenocarcinoma cells expressed cytokeratin
19 and beta-catenin in their cytoplasm, with E-cadherin and CD44s at the plasma
membrane. In the round cells, cytokeratin 19 and vimentin was detected in their
cytoplasm and CD44s at the plasma membrane. E-cadherin immunoreactivity was
weakly present in their cytoplasm and beta-catenin was negative. Loss or
reduction of the E-cadherin and beta-catenin expressions and overexpression of
CD44s in the round cells are suggested to be contributed to the high propensity
for lymphatic permeation and poor prognosis.
PMID- 17033800
TI - Utilization of low-dose multidetector CT and virtual bronchoscopy in children
with suspected foreign body aspiration.
AB - BACKGROUND: Foreign body aspiration is common in children, especially those under
3 years of age. Chest radiography and CT are the main imaging modalities for the
evaluation of these children. Management of children with suspected foreign body
aspiration (SFBA) mainly depends on radiological findings. OBJECTIVE: To
investigate the potential use of low-dose multidetector CT (MDCT) and virtual
bronchoscopy (VB) in the evaluation and management of SFBA in children. MATERIALS
AND METHODS: Included in the study were 37 children (17 girls, 20 boys; age 4
months to 10 years, mean 32 months) with SFBA. Chest radiographs were obtained
prior to MDCT in all patients. MDCT was performed using a low-dose technique. VB
images were obtained in the same session. Conventional bronchoscopy (CB) was
performed within 24 h on patients in whom an obstructive abnormality had been
found by MDCT and VB. RESULTS: Obstructive pathology was found in 16 (43.25%) of
the 37 patients using MDCT and VB. In 13 of these patients, foreign bodies were
detected and removed via CB. The foreign bodies were located in the right main
bronchus (n = 5), in the bronchus intermedius (n = 6), in the medial segment of
the middle lobe bronchus (n = 1), and in the left main bronchus (n = 1). In the
remaining three patients, the diagnosis was false-positive for an obstructive
pathology by MDCT and VB; the final diagnoses were secretions (n = 2) and
schwannoma (n = 1), as demonstrated by CB. In 21 patients in whom no obstructive
pathology was detected by MDCT and VB, CB was not performed. These patients were
followed for 5-20 months without any recurrent obstructive symptomatology.
CONCLUSIONS: Low-dose MDCT and VB are non-invasive radiological modalities that
can be used easily in the investigation of SFBA in children. MDCT and VB provide
the exact location of the obstructive pathology prior to CB. If obstructive
pathology is depicted with MDCT and VB, CB should be performed either for
confirmation of the diagnosis or for the diagnosis of an alternative cause for
the obstruction. In cases where no obstructive pathology is detected by MDCT and
VB, CB may not be clinically useful.
PMID- 17033801
TI - Savanna fires increase rates and distances of seed dispersal by ants.
AB - Myrmecochory (seed dispersal by ants) is a prominent dispersal mechanism in many
environments, and can play a key role in local vegetation dynamics. Here we
investigate its interaction with another key process in vegetation dynamics-fire.
We examine ant dispersal of seeds immediately before and after experimental
burning in an Australian tropical savanna, one of the world's most fire-prone
ecosystems. Specifically, our study addressed the effects of burning on: (1) the
composition of ants removing seeds, (2) number of seed removals, and (3) distance
of seed dispersal. Fire led to higher rates of seed removal post-fire when
compared with unburnt habitat, and markedly altered dispersal distance, with mean
dispersal distance increasing more than twofold (from 1.6 to 3.8 m), and many
distance dispersal events greater than the pre-fire maximum (7.55 m) being
recorded. These changes were due primarily to longer foraging ranges of species
of Iridomyrmex, most likely in response to the simplification of their foraging
landscape. The significance of enhanced seed-removal rates and distance dispersal
for seedling establishment is unclear because the benefits to plants in having
their seeds dispersed by ants in northern Australia are poorly known. However, an
enhanced removal rate would enhance any benefit of reduced predation by rodents.
Similarly, the broader range of dispersal distances would appear to benefit
plants in terms of reduced parent-offspring conflict and sibling competition, and
the location of favourable seedling microsites. Given the high frequency of fire
in Australian tropical savannas, enhanced benefits of seed dispersal by ants
would apply for much of the year.
PMID- 17033802
TI - Is microbial community composition in boreal forest soils determined by pH, C-to
N ratio, the trees, or all three?
AB - In Fennoscandian boreal forests, soil pH and N supply generally increase downhill
as a result of water transport of base cations and N, respectively.
Simultaneously, forest productivity increases, the understory changes from
ericaceous dwarf shrubs to tall herbs; in the soil, fungi decrease whereas
bacteria increase. The composition of the soil microbial community is mainly
thought to be controlled by the pH and C-to-N ratio of the substrate. However,
the latter also determines the N supply to plants, the plant community
composition, and should also affect plant allocation of C below ground to roots
and a major functional group of microbes, mycorrhizal fungi. We used phospholipid
fatty acids (PLFAs) to analyze the potential importance of mycorrhizal fungi by
comparing the microbial community composition in a tree-girdling experiment,
where tree belowground C allocation was terminated, and in a long-term (34 years)
N loading experiment, with the shifts across a natural pH and N supply gradient.
Both tree girdling and N loading caused a decline of ca. 45% of the fungal
biomarker PLFA 18:2omega6,9, suggesting a common mechanism, i.e., that N loading
caused a decrease in the C supply to ectomycorrhizal fungi just as tree girdling
did. The total abundance of bacterial PLFAs did not respond to tree girdling or
to N loading, in which cases the pH (of the mor layer) did not change
appreciably, but bacterial PLFAs increased considerably when pH increased across
the natural gradient. Fungal biomass was high only in acid soil (pH < 4.1) with a
high C-to-N ratio (>38). According to a principal component analysis, the soil C
to-N ratio was as good as predictor of microbial community structure as pH. Our
study thus indicated the soil C-to-N ratio, and the response of trees to this
ratio, as important factors that together with soil pH influence soil microbial
community composition.
PMID- 17033804
TI - Successful treatment of Wolman disease by unrelated umbilical cord blood
transplantation.
AB - Wolman disease is a rapidly fatal lysosomal storage disease caused by the
complete absence of lysosomal acid lipase activity. We report the cure of an
infant with Wolman disease following transplantation of unrelated HLA-mismatched
umbilical cord blood-derived stem cells. Umbilical cord blood was chosen as the
stem-cell source because of its immediate availability and reduced tendency to
cause graft-versus-host disease. The transplantation resulted in restoration of
normal acid lipase levels before the onset of permanent end-organ damage. Four
years after transplantation, the patient is thriving and has normal levels of
acid lipase in peripheral blood cells. To our knowledge, this is the first report
of a successful unrelated cord blood transplant in a patient with Wolman disease.
Umbilical cord stem cells transplantation can restore acid lipase levels in
Wolman disease, and if performed early, can cure the disease.
PMID- 17033803
TI - Variations in prevalence of attention deficit hyperactivity disorder worldwide.
AB - Attention deficit hyperactivity disorder (ADHD) is among the most common,
intensely investigated, and yet diagnostically controversial neurobehavioral
conditions of childhood. The prevalence of ADHD has been reported with great
variations among different studies, ranging from 2.2% to 17.8%. The aim of this
review was to investigate the variables that influence the prevalence of ADHD and
to derive a best estimate for the prevalence of the disorder. We reviewed all the
39 studies on ADHD prevalence appearing in the Pubmed and published since 1992.
These studies indicate that ADHD is more common in boys than girls, in younger
than older children and adolescents, in one-setting rather than two-setting
screening studies, in studies based on DSM-IV rather than DSM-III-R criteria.
Additional factors that may well influence prevalence rates include source of
information and assessment of clinical impairment. In conclusion, our findings
suggest that population characteristics, methodology features, ethnic and
cultural differences and diagnostic criteria involved in studies affect the
prevalence of ADHD. Standardized designs may lead to firm conclusions on the true
prevalence of ADHD, the estimation of which seems impossible to be achieved by
reviewing the already existing literature.
PMID- 17033805
TI - Slow-growing lambdoid melanotic neuroectodermal tumor of infancy.
AB - Melanotic neuroectodermal tumors of infancy are rare neoplasms that occasionally
may involve the skull. Usually such lesions present as an anterior fontanelle
mass that grows rapidly. Very rarely, skull lesions are located at different
sites and have an indolent course, thus making the diagnosis more difficult. To
illustrate this latter presentation, we present a case of a slowly growing
melanotic neuroectodermal tumor of infancy located on the right lambdoid suture.
PMID- 17033806
TI - Impact of amoxicillin, associated or not with clavulanic acid, on pharyngeal
colonization and selection of Streptococcus pneumoniae resistance in children
under 5 years of age.
AB - Among young children, pneumococcal nasopharyngeal colonization (NPC) rates of
>90% have been described. The aim of our study was to assess the effect of
amoxicillin exposure on the NPC. From Dec 2001 to Feb 2004, less than 5 years old
children with respiratory symptoms and fever who were prescribed amoxicillin were
eligible. Three nasopharyngeal swabs were taken: at the time of the initial visit
(IV), 60 hours after amoxicillin discontinuation (end of treatment visit, ETV),
and 4 weeks later (follow-up visit, FUV). One hundred and thirty four children
were included. NPC was detected in 58.5%, 42.9% and 51% of <1, 1-2 and >2 years
old children respectively (NS). Vaccine serotypes (VS) or vaccine-related
serotypes (VRS) were identified in 80%, 40% and 55% of <1-year-old, 1-2 year-old
and >2-year-old children respectively (NS). The proportion of PNSSP was 60% in <1
year-old children, 43% in 1-2 year-old children and 40% in >2-year-old children
(NS). 49 out of 134 (36.5%) children completed the three study visits. 51%, 22.4%
and 46.9% of those were colonized at IV, ETV and FUV, respectively (p=0.007). The
percentage of resistant SP was 28%, 45.5% and 8.7% (p=0.05) for penicillin. In
children <1 year of age, a higher proportion of SP colonization, presence of VS
and PNSSP was found. A downfall of NPC at the end of therapy was observed. NPC
returned to baseline levels thanks to "de novo" colonization in half of the
cases, a few weeks after.
PMID- 17033807
TI - Predictive risk factors for coronary artery abnormalities in Kawasaki disease.
AB - Clinical characteristics to predict the development of coronary artery
abnormalities (CAA) in Kawasaki disease (KD) were assessed by reviewing medical
records of patients diagnosed with KD at Korea University Medical Center from
March 2001 to February 2005. Of the 285 patients diagnosed with KD, 19 developed
CAA (6.7%). Compared with the CAA(-) group, the CAA(+) group had a longer
duration of fever after intravenous gamma-globulin (IVGG) injection (2.4+/-2.9
vs. 1.5+/-1.2 days, p=0.008) and higher C-reactive protein (CRP)(12.3+/-7.8 vs.
8.7+/-7.1 mg/dL, p=0.038). In particular, the CAA(+) group tended to have more
than 7 days of fever before IVGG and more than 3 days of fever after IVGG (26.3
vs. 5.3%, p<0.001; 26.3 vs. 6.4%, p=0.002). When the IVGG responsiveness was
defined by the presence of defervescence within 3 days after IVGG, IVGG-non
responders showed a higher incidence of CAA (22.7 vs. 5.3%, p=0.002). Non
responders had a longer duration of fever after IVGG (5.5+/-1.9 vs. 1.2+/-0.6
days, p<0.001) and a significantly increased CRP, AST, ALT and total bilirubin.
Multivariate regression analysis for CAA showed that the only factor
significantly associated with the development of CAA was total fever that lasted
for longer than 8 days (OR=4.052, 95% CI=1.151-14.263, p=0.0293). Conclusively,
the most important predictor of CAA in KD is total duration of fever longer than
8 days. Early identification of IVGG non-responders and active therapeutic
intervention for fever in KD cases might decrease the incidence of CAA.
PMID- 17033808
TI - Ecotype-specific and chromosome-specific expansion of variant centromeric
satellites in Arabidopsis thaliana.
AB - Despite the conserved roles and conserved protein machineries of centromeres,
their nucleotide sequences can be highly diverse even among related species. The
diversity reflects rapid evolution, but the underlying mechanism is largely
unknown. One approach to monitor rapid evolution is examination of intra-specific
variation. Here we report variant centromeric satellites of Arabidopsis thaliana
found through survey of 103 natural accessions (ecotypes). Among them, a cluster
of variant centromeric satellites was detected in one ecotype, Cape Verde Islands
(Cvi). Recombinant inbred mapping revealed that the variant satellites are
distributed in centromeric region of the chromosome 5 (CEN5) of this ecotype.
This apparently recent variant accumulation is associated with large deletion of
a pericentromeric region and the expansion of satellite region. The variant
satellite was bound to HTR12 (centromeric variant histone H3), although expansion
of the satellite was not associated with comparable increase in the HTR12
binding. The results suggest that variant satellites with centromere function can
rapidly accumulate in one centromere, supporting the model that the satellite
repeats in the array are homogenized by occasional unequal crossing-over, which
has a potential to generate an expansion of local sequence variants within a
centromere cluster.
PMID- 17033809
TI - Structure and transcriptional impact of divergent repetitive elements inserted
within Phanerochaete chrysosporium strain RP-78 genes.
AB - We describe the structure, organization, and transcriptional impact of repetitive
elements within the lignin-degrading basidiomycete, Phanerochaete chrysosporium.
Searches of the P. chrysosporium genome revealed five copies of pce1, a ~1,750-nt
non-autonomous, class II element. Alleles encoding a putative glucosyltransferase
and a cytochrome P450 harbor pce insertions and produce incomplete transcripts.
Class I elements included pcret1, an intact 8.14-kb gypsy-like retrotransposon
inserted within a member of the multicopper oxidase gene family. Additionally, we
describe a complex insertion of nested transposons within another putative
cytochrome P450 gene. The disrupted allele lies within a cluster of >14 genes,
all of which encode family 64 cytochrome P450s. Components of the insertion
include a disjoint copia-like element, pcret3, the pol domain of a second
retroelement, pcret2, and a duplication of an extended ORF of unknown function.
As in the case of the pce elements, pcret1 and pcret2/3 insertions are confined
to single alleles, transcripts of which are truncated. The corresponding wild
type alleles are apparently unaffected. In aggregate, P. chrysosporium harbors a
complex array of repetitive elements, at least five of which directly influence
expression of genes within families of structurally related sequences.
PMID- 17033810
TI - Molecular genetic analysis of five spike-related traits in wheat using RIL and
immortalized F2 populations.
AB - Kernel number per spike is one of the most important yield components of wheat.
To map QTLs related to kernel number including spike length (SPL), spikelet
number per spike (SPN), fertile spikelet number (FSPN), sterile spikelet number
(SSPN) and compactness, and to characterize the inheritance modes of the QTLs and
two-locus interactions, 136 recombinant inbred lines (RILs) derived from
'Nanda2419' x 'Wangshuibai' and an immortalized F(2 )population (IF(2)) generated
by randomly permutated intermating of these RILs were investigated. QTL mapping
made use of the previously constructed over 3300 cM linkage map of the RIL
population. Three, five, two, two and six chromosome regions were identified,
respectively, for their association with SPL, SPN, FSPN, SSPN, and compactness in
at least two of the three environments examined. All compactness QTLs but one
shared the respective intervals of QSpn.nau-5A and the SPL QTLs. Xcfd46-Xwmc702
interval on chromosome 7D was related to all traits but SSPN and had consistently
the largest effects. The fact that not all the compactness QTL intervals were
related to both SPL and SPN indicates that compactness is regulated by different
mechanisms. Interval coincidence between QTLs of SPL and SPN and between QTLs of
FSPN and SSPN was minimal. For all the traits, favorable alleles exist in both
parents. Inheritance modes from additiveness to overdominance of the QTLs were
revealed and two-locus interactions were detected, implying that the traits
studied are under complex genetic control. The results could contribute to wheat
yield improvement and better use of Wangshuibai and Nanda2419 the two special
germplasms in wheat breeding program.
PMID- 17033811
TI - Genome-wide analysis of the stress associated protein (SAP) gene family
containing A20/AN1 zinc-finger(s) in rice and their phylogenetic relationship
with Arabidopsis.
AB - Proteins with the A20/AN1 zinc-finger domain are present in all eukaryotes and
are well characterized in animals, but little is known about their function in
plants. Earlier, we have identified an A20/AN1 zinc-finger containing stress
associated protein 1 gene (SAP1) in rice and validated its function in abiotic
stress tolerance. In this study, genome-wide survey of genes encoding proteins
possessing A20/AN1 zinc-finger, named SAP gene family, has been carried out in
rice and Arabidopsis. The genomic distribution and gene architecture as well as
domain structure and phylogenetic relationship of encoded proteins numbering 18
and 14 in rice and Arabidopsis, respectively, have been studied. Expression
analysis of the rice SAP family was done to investigate their response under
abiotic stress conditions. All the genes were inducible by one or the other
abiotic stresses indicating that the OsSAP gene family is an important component
of stress response in rice. Manipulation of their expression and identification
of their superior alleles should help confer stress tolerance in target crops.
PMID- 17033812
TI - Phosphate starvation responses are mediated by sugar signaling in Arabidopsis.
AB - Phosphate (Pi) is one of the least available plant nutrients in soils. It is
associated with dynamic changes in carbon fluxes and several crucial processes
that regulate plant growth and development. Pi levels regulate the expression of
large number of genes including those involved in photosynthesis and carbon
metabolism. Herein we show that sugar is required for Pi starvation responses
including changes in root architecture and expression of phosphate starvation
induced (PSI) genes in Arabidopsis. Active photosynthesis or the supplementation
of sugar in the medium was essential for the expression of PSI genes under Pi
limiting conditions. Expression of these genes was not only induced by sucrose
but also detected, albeit at reduced levels, with other metabolizable sugars. Non
metabolizable sugar analogs did not induce the expression of PSI genes. Although
sugar input appears to be down-stream of initial Pi sensing, it is absolutely
required for the completion of the PSI signaling pathway. Altered expression of
PSI genes in the hexokinase signaling mutant gin2 indicates that hexokinase
dependent signaling is involved in this process. The study provides evidence for
requirement of sugars in PSI signaling and evokes a role for hexokinase in some
components of Pi response mechanism.
PMID- 17033813
TI - Sustained beneficial effect of intravenous bisphosphonates after their
discontinuation in children.
AB - We studied if the beneficial effects of bisphosphonates are maintained after
their discontinuation, and whether adverse effects may develop. Seventeen
children in whom I.V. bisphosphonates were discontinued for at least 12 months
were included. Fracture rate (FR), skeletal pain, bone mineral density of total
body (TB) and spine L(2-4), skeletal radiographs, bone markers and kidney
functions were compared between: (a) before treatment, (b) end of treatment, and
(c) last follow-up. Mean treatment duration was 22+/-2 months (6-43) and follow
up 26+/-2 months (18-44). FR (mean +/- SD) decreased from 0.74+/-0.21/year before
treatment to 0.35+/-0.11/year after treatment and 0.20+/-0.09/year at follow-up
(p<0.05). Three children had bone pain before treatment, six during treatment and
none at end of follow-up (p<0.05). TB Z-score increased from -1.24+/-0.50 at
baseline to -0.37+/-0.44 at end of treatment and -0.39+/-0.37 at follow-up
(p<0.05). Spinal Z-score increased from -1.65+/-0.57 to -0.34+/-0.56 and 0.19+/
0.49, respectively (p<0.05). Bone turnover markers showed sustained effect of
bisphosphonates. No adverse effects on kidney functions or skeletal radiographs
were noted. We conclude that I.V. bisphosphonates continue to exert their
beneficial effect for a mean of 26+/-2 months after their discontinuation;
therefore, once therapeutic goals are achieved, the medication can be withheld,
followed by periodic re-evaluation.
PMID- 17033814
TI - Optical mapping of V(m) and Ca(i)(2+) in a model of arrhythmias induced by local
catecholamine application in patterned cell cultures.
AB - Catecholamines are known to provoke cardiac arrhythmias, but important aspects
such as localization of the arrhythmia source in multicellular tissue and exact
ionic mechanisms are not well-known. In this work, a multicellular model of
arrhythmias caused by local epinephrine application was developed; V (m) and
Ca(i)(2+) changes at the arrhythmia source were measured using fluorescent dyes
and high-resolution optical mapping. Cultured strands of neonatal rat myocytes
(width approximately 0.4 mm) were produced by patterned growth. Epinephrine (1
micromol/l) was applied over an area of 0.3-0.6 mm via two micropipettes, and
strands were stimulated by burst pacing. Local epinephrine application caused
triggered arrhythmias with cycle lengths of 202-379 ms and duration of >10 s in 9
out of 16 preparations. Optical V(m) mapping demonstrated that in 78% of cases,
the source of arrhythmia was located at the boundary of the locally perfused
area. Staining with Ca(i)(2+)-sensitive dye Fluo-4 prevented arrhythmia induction
in most cases (85%) likely due to Ca(2+) buffering by the dye. Optical Ca(i)(2+)
mapping revealed non-propagated Ca(i)(2+) oscillations at the boundary of the
locally perfused area in 45% cases. In conclusion, we developed a new model of
catecholamine-dependent arrhythmias allowing mapping of V(m) and Ca(i)(2+) at the
arrhythmia source with microscopic resolution. The arrhythmias typically
originated from the boundary of the epinephrine-perfused area. The location of
the arrhythmia source correlated with localized Ca(i)(2+) oscillations suggesting
that arrhythmias were caused by Ca(i)(2+) overload at these locations.
PMID- 17033815
TI - Rooting and vitality of poinsettia cuttings was increased by arbuscular
mycorrhiza in the donor plants.
AB - In this paper, we provide evidence that the rooting performance of cuttings can
be improved by the arbuscular mycorrhizal (AM) symbiosis of donor plants.
Poinsettia stock plants were inoculated with the Glomus intraradices isolate H510
and grown in three different cultivation systems (two organic and one
conventional). AM colonization was not related to P availability in the
substrate. Decay of the excised cuttings in response to unfavorable postharvest
storage conditions was significantly reduced by AM colonization of the stock
plants. In most cases, AM significantly promoted the formation of adventitious
roots in the stored cuttings. The strongest effect of AM was found when donor
plants were grown in a modified organic substrate; then AM-conditioned cuttings
showed higher leaf sugar levels and a changed kinetic of carbohydrates during
storage. Analyses of N, P, and K in cuttings did not indicate a nutritional
effect. The results support the idea that an altered carbohydrate metabolism and
plant hormones can contribute to improved rooting performance of cuttings excised
from mycorrhizal donor plants.
PMID- 17033816
TI - The ectomycorrhizal fungus Scleroderma bermudense alleviates salt stress in
seagrape (Coccoloba uvifera L.) seedlings.
AB - The purpose of this study was to test the capacity of the ectomycorrhizal (ECM)
fungus, Scleroderma bermudense, to alleviate saline stress in seagrape (Coccoloba
uvifera L.) seedlings. Plants were grown over a range (0, 200, 350 and 500 mM) of
NaCl levels for 12 weeks, after 4 weeks of non-saline pre-treatment under
greenhouse conditions. Growth and mineral nutrition of the seagrape seedlings
were stimulated by S. bermudense regardless of salt stress. Although ECM
colonization was reduced with increasing NaCl levels, ECM dependency of seagrape
seedlings increased. Tissues of ECM plants had significantly increased
concentrations of P and K but lower Na and Cl concentrations than those of non
ECM plants. Higher K concentrations in the leaves of ECM plants suggested a
higher osmoregulating capacity of these plants. Moreover, the water status of ECM
plants was improved despite their higher evaporative leaf surface. The results
suggest that the reduction in Na and Cl uptake together with a concomitant
increase in P and K absorption and a higher water status in ECM plants may be
important salt-alleviating mechanisms for seagrape seedlings growing in saline
soils.
PMID- 17033817
TI - Zinc-tolerant Suillus bovinus improves growth of Zn-exposed Pinus sylvestris
seedlings.
AB - Scots pine (Pinus sylvestris L.) seedlings inoculated or not (NM) by a Zn
sensitive or a Zn-tolerant isolate of the ectomycorrhizal fungus Suillus bovinus
(L. Fr.) Roussel were exposed to 0.1 or 150 muM Zn(2+) for 9 months. We
hypothesized that inoculation with a Zn-tolerant S. bovinus isolate should result
in added Zn resistance of the host plant. Plant and fungal growth as well as
nutrient profiles and photosynthetic pigments in pine needles were quantified. In
NM plants and in plants colonized by the Zn-sensitive isolate, plant growth, N,
P, Mg and Fe assimilation were strongly inhibited under Zn stress and concurred
with significantly reduced chlorophyll concentrations. In contrast, plants
colonized by the Zn-tolerant isolate grew much better and remained
physiologically healthier when exposed to elevated Zn. These results provide
further evidence for the important role metal-adapted mycorrhizal fungi play as
an effective biological barrier against metal toxicity in trees.
PMID- 17033818
TI - Cytoplasmic Clb2 is required for timely inactivation of the mitotic inhibitor
Swe1 and normal bud morphogenesis in Saccharomyces cerevisiae.
AB - Subcellular localization is an important determinant of substrate and functional
specificity for cyclin-cyclin dependent kinase (CDK) complexes. This work
addresses the cytoplasmic function of the budding yeast mitotic cyclin Clb2,
which is mostly nuclear but is also present in the bulk cytoplasm and at the
mother-bud neck. Clb2 contains two leucine-rich nuclear export signals (NESs)-
one of which we newly describe here--that maintain its presence in the cytoplasm.
Yeast strains bearing mutations in one or both of these NESs have elongated buds,
indicative of a G2/M cell cycle delay. A small number of these cells exhibit a
filamentous-like morphology under conditions that do not normally induce
filamentous growth. These phenotypes are enhanced by deletion of the other three
mitotic cyclins (CLB1,3,4) and are dependent on expression of Swe1, the yeast
Cdk1 inhibitory kinase. Deltaclb1,3,4 Deltabud3 cells, which fail to localize
Clb2 to the bud neck, also exhibit a Swe1-dependent elongated bud phenotype. Our
results support a model in which cytoplasmic Clb2-Cdk1 is required for timely
inactivation of Swe1 at the G2/M transition and bud neck targeting of Clb2
contributes to the efficiency of this process. Cytoplasmic Clb2 may also be
important for repression of filamentous growth.
PMID- 17033819
TI - RNA editing site recognition in heterologous plant mitochondria.
AB - RNA editing is a process that modifies the information content of mitochondrial
messenger RNAs in flowering plants changing specific cytosine residues into
uridine. To gain insight into editing site recognition, we used electroporation
to introduce engineered wheat (Triticum aestivum) or potato (Solanum tuberosum)
mitochondrial cox2 genes, and an atp9-containing chimeric gene, into non-cognate
mitochondria, and observed the efficiency of editing in these contexts. Both
wheat and potato mitochondria were able to express "foreign" constructs, and
their products were properly spliced. Seventeen and twelve editing sites are
present in the coding regions of wheat and potato cox2 transcripts, respectively.
Eight are common to both plants, whereas nine are specific to wheat, and four to
potato. An analogous situation is found for the atp9 mRNA coding regions from
these species. We found that both mitochondria were able to recognize sites that
are already present as T at the genomic level, making RNA editing unnecessary for
that specific residue in the cognate organelle. Our results demonstrate that non
cognate mitochondria are able to edit residues that are not edited in their own
transcripts, and support the hypothesis that the same trans-acting factor may
recognize several editing sites.
PMID- 17033820
TI - Mitochondrial haplogroup N9b is protective against myocardial infarction in
Japanese males.
AB - Superoxide, which mitochondria mainly produce in vascular endothelial cells,
plays an important role in the pathogenesis of atherosclerosis and coronary
artery disease. Accordingly, mitochondrial functional differences are thought to
be one of the most important factors for the risk of myocardial infarction among
various individuals. In the present study, we surveyed mitochondrial haplogroups
associated with myocardial infarction in Japanese subjects. The study population
comprised 2,137 unrelated Japanese individuals, including 1,181 subjects with a
first myocardial infarction (920 males, 261 females) and the control subjects
(522 males, 434 females). Twenty-eight mitochondrial single nucleotide
polymorphisms of 12 major mitochondrial haplogroups (A, B, D4, D5, F, G1, G2,
M7a, M7b, M7c, N9a, and N9b) were determined by use of 28-plex PCR and
fluorescent beads combined with sequence-specific oligonucleotide probes. After
adjustment for age, sex, body mass index, and prevalence of smoking,
hypertension, hypercholesterolemia, and type 2 diabetes, a significantly (P =
0.0019) lower prevalence of haplogroup N9b was detected in subjects with
myocardial infarction than in the controls. Especially, the prevalence of this
haplogroup was significantly lower (P = 0.0007) in the male subjects with the
disease than in the male controls. In contrast, there were trends towards higher
prevalence of the disease in haplogroup G1 for males (P < 0.05). No significant
haplogroup-related associations were detected for females. Our data suggest that
haplogroup N9b confers resistance against myocardial infarction in Japanese
males.
PMID- 17033821
TI - An improved RT-PCR method for the detection of killer-cell immunoglobulin-like
receptor (KIR) transcripts.
AB - Killer cell immunoglobulin-like receptors (KIRs) are expressed on human natural
killer (NK) cells and a proportion of T cells. As the specificity of these NK and
T cells is, at least in part, determined by the combination of KIRs they express,
it is important to be able to determine the KIR expression pattern of NK and T
cell clones to understand their function. However, for most KIR genes, specific
reagents to detect expression are currently either unavailable or sensitive to
allelic variations. In this study, a reverse transcriptase-polymerase chain
reaction (RT-PCR) that uses new primer sets for the gene-specific detection of
KIR transcripts is presented and validated. The key advantage of this RT-PCR
method over previously published ones is that it was designed to detect
transcripts of all confirmed allelic variants of the KIR genes, while remaining
gene-specific.
PMID- 17033822
TI - Association of interferon-gamma gene haplotype in the Chinese population with
hepatitis B virus infection.
AB - In general, cytokines encoded by different genes of human genome might strongly
influence host cell-mediated immune responses, which play an important role in
the clearance of virus by the infected host. Interferon gamma (IFN-gamma)
produced by T lymphocytes and natural killer cells plays an essential role in
affecting cellular immune responses. A functional study demonstrated that two
single nucleotide polymorphisms located in the IFN-gamma gene intron (at
positions +874 and +2109) were involved in its transcriptional regulation. The
aim of this study was to evaluate whether IFN-gamma gene polymorphisms or its
haplotypes might be associated with predisposition to hepatitis B virus (HBV)
infection in the Chinese population. The study included 181 cases with HBV
infection and 272 gender, age-matched healthy controls. All genotyping were
identified by polymerase chain reaction in association with the measurement of
amplification refractory mutation system. A significant difference was observed
between case and control groups. The frequency of +874A allele was significantly
higher in patients than in controls (OR = 2.25, 95%CI = 1.69-2.99, P < 0.0001).
However, no significant difference was found in the allelic frequencies of IFN
gamma +2109A/G between cases and controls (P > 0.05). By haplotype analysis, the
frequency of haplotype AG (+874A and +2109G) revealed a significant difference in
the cases in comparison to controls (P < 0.0001). Multiple logistic regression
analysis showed that individuals possessing haplotype AG had an increased
likelihood of HBV infection (OR = 8.14, 95%CI = 4.98-13.30). Our results suggest
that haplotype AG containing +874A and +2109G may be a crucial risk factor of
genetic susceptibility to HBV infection in the Chinese population.
PMID- 17033823
TI - Genetic variants of the IgA Fc receptor (FcalphaR, CD89) promoter in chronic
hepatitis C patients.
AB - Fc receptor for IgA (FcalphaR, CD89) is capable of triggering IgA-mediated immune
responses to pathogens and has been proposed to function in circulating IgA
clearance. Because inheritable variations modifying individual immune responses
or immunoglobulin catabolism may affect the chronicity of viral infection, we
investigated whether promoter polymorphisms of the FcalphaR gene (FCAR) affect
chronic hepatitis C virus (HCV) infection and its disease progression. The two
311T/C and -142T/C single-nucleotide polymorphisms (SNPs) were studied by direct
DNA sequencing in 177 Japanese patients with chronic hepatitis C (CHC). Both
311CC and -142CC genotypes were more frequent in CHC patients (15.9 and 18.6%)
compared with 210 healthy controls (5.7 and 10.0%) [p = 0.001, odds ratio (OR) =
3.10, 95% confidence interval CI) = 1.53-6.30 and p = 0.014, OR = 2.06, 95% CI =
1.14-3.72, respectively], and were associated with infection with HCV genotype
2a/2b (p = 0.019 and p = 0.005, respectively). Conversely, -311CC and -142CC were
decreased in 59 patients at advanced stages of disease as assessed on the basis
of hepatic fibrosis markers such as decreased platelet count (PLT) (<
150,000/microl) (5.1 and 8.5%) compared with 91 patients with normal PLT (> or =
150,000/microl) (24.2 and 26.4%) (p = 0.006 and p = 0.005, respectively).
Moreover, among the patients with normal PLT (but not with decreased PLT), -311CC
or -142CC was significantly associated with decreased serum IgA levels (p = 0.023
or p = 0.007, respectively). These results suggest that the FCAR promoter SNPs
may be related to chronic HCV infection and disease progression in Japanese CHC,
which might be explained by altered FcalphaR expression affecting IgA-mediated
immune responses and/or IgA catabolism.
PMID- 17033824
TI - Mhc class I genes of the cichlid fish Oreochromis niloticus.
AB - In terms of number of species, perciform (perch-like) fishes are one of the most
diversified groups of modern vertebrates. Within this group, the family Cichlidae
is best known for its spectacular adaptive radiation in the great lakes of East
Africa. The molecular tool kit used in the study of this radiation includes the
major histocompatibility complex (Mhc) genes. To refine this tool, information
about the organization of the Mhc regions is badly needed. In this study, the
first step was taken toward providing such information for the Mhc class one
regions of Oreochromis niloticus, a representative species of the tilapiine
branch of the Cichlidae, for which good bacterial artificial chromosome library
is available. Screening of the library with class I gene probes led to the
identification and isolation of 31 class-I-positive clones. Sequencing of one of
these clones and partial characterization of the remaining clones for the
presence of class I exons resulted in the construction of two contigs
representing the class I region of this species as well as identification of
seven additional class-I-positive singleton clones. The O. niloticus genome was
shown to contain at least 28 class I genes or gene fragments. The shorter of the
two contigs was approximately 330 kb long and contained eight class I genes/gene
fragments; the longer contig encompassed 1,200 kb of sequence and contained
minimally 17 class I genes/gene fragments; three additional class I genes were
found to be borne by a clone that might be part of the shorter contig.
PMID- 17033825
TI - Production of soft rot resistant calla lily by expressing a ferredoxin-like
protein gene (pflp) in transgenic plants.
AB - An efficient protocol for the Agrobacterium tumefaciens-mediated transformation
of calla lily (Zantedeschia elliottiana (W. Wats.) Engl. cultivar 'Florex Gold')
is described. Shoot basal discs were co-cultivated with A. tumefaciens C58C1
carrying a plasmid containing neomycin phosphotransferase (nptII) and plant
ferredoxin-like protein (pflp) genes. After Agrobacterium co-cultivation, the
shoot basal discs were exposed to 100 mg l(-1) kanamycin for selection. Twenty
eight out of 260 discs (10.8%) were found to have survived and produced shoot
clusters. Twenty-six of these were confirmed to contain the pflp transgene by
PCR, ending up in 10% transformation efficiency. The disease resistance
investigation revealed that 18 transgenic plants exhibited resistance to soft rot
disease caused by Erwinia carotovora subsp. carotovora. The presence of pflp gene
was demonstrated by PCR, and its accumulation and activity was confirmed by
Western blot and disease resistance assay. This was the first report to show the
successful transformation and resistance to a bacterial pathogen in Zantedeschia.
The protocol is useful for the quality improvement of calla lily through genetic
transformation.
PMID- 17033826
TI - The effects of dietary phosphorus deficiency on surface pH and membrane
composition of the mucosa epithelium in caprine jejunum.
AB - In ruminants, the uptake of inorganic phosphate (P(i)) across the intestinal
mucosa epithelium by Na-dependent and Na-independent mechanisms is a main
regulatory factor in P homeostasis. The aim of the study was to elucidate to
which extent Na-independent mechanisms, including pH effects or composition of
mucosal brush-border membranes, could be involved in positive stimulation of P(i)
absorptive processes seen under the P deficient condition. Therefore, luminal,
surface and intracellular pH of the jejunal epithelial cells in control and P
depleted goats were compared and biochemical analyses of membrane phospholipids
in the apical membrane of the jejunal epithelium were performed. Dietary P
depletion resulted in decreased plasma P(i) levels. While pH in jejunal ingesta
was not significantly changed, P depletion resulted in a significantly lower
surface pH in the crypt region compared to control animals (7.62 +/- 0.02 vs.
7.77 +/- 0.04, n = 4, P < 0.01). Inhibition of apical Na(+)/H(+)-exchange
resulted in an increase of the jejunal surface pH in P depleted animals by 0.07
+/- 0.01 (n = 6, P < 0.01) and 0.05 +/- 0.01 (n = 6, P < 0.01) for the villus and
the crypt region, respectively. This increase were inversely correlated with the
initial surface pH prior to inhibition. In contrast to surface pH, intracellular
pH of the jejunal epithelium and the phospholipid composition of the apical
jejunal membrane were not affected by P depletion. Although the data suggest the
existence of a Na(+)/H(+)-exchange mechanism at the luminal surface of goat
jejunum they do not support the hypothesis that adaptational processes of active
P(i) absorption from goat jejunum in response to low dietary P could be based on
"non P(i) transporter events".
PMID- 17033827
TI - Interactions of human tenascin-X domains with dermal extracellular matrix
molecules.
AB - Tenascin-X (TNX) is a large 450 kDa extracellular matrix protein expressed in a
variety of tissues including skin, joints and blood vessels. Deficiency of TNX
causes a recessive form of Ehlers-Danlos syndrome characterized by joint
hypermobility, skin fragility and hyperextensible skin. Skin of TNX deficient
patients shows abnormal elastic fibers and reduced collagen deposition. The
mechanism by which TNX deficiency leads to connective tissue alterations is
unknown. Here we report that C-terminal domains of human TNX bind to major dermal
fibrillar collagens and tropoelastin. We have mapped these interactions to the
fibronectin type III repeat 29 (FNIII29) and the C-terminal fibrinogen domain
(FbgX) of TNX. In addition we found that FNIII29 of TNX accelerates collagen
fibrillogenesis in vitro. We hypothesize that TNX contributes to matrix stability
and is possibly involved in collagen fibril formation.
PMID- 17033828
TI - Effects of unilateral vocal cord paralysis on objective voice measures obtained
by Praat.
AB - Unilateral vocal cord paralysis (VCP) affects the objective properties of voice
by diminished neurologic control and degenerative changes in laryngeal tissue.
The goal of this study was to compare the acoustic parameters of VCP patients
with control volunteers using the software Praat. Acoustic analysis results of 18
unilateral VCP patients were compared with age and sex matched 72 normal adult
volunteers. Comparison of acoustic analysis results of male and female VCP
patients with their age and sex matched control groups revealed statistically
significant difference in jitter, shimmer, and noise-to-harmonics ratio values (P
< 0.01) in both groups. There were no differences in mean fundamental frequency
and intensity values. We conclude that these differences were in accordance with
the results obtained by commercially available voice analysis programs. This
study reflects the first results obtained with Praat software in VCP patients.
Using the software Praat, is free and easy, that supports the clinician to rely
on objective scientific data.
PMID- 17033829
TI - Idiopathic laryngeal spasm: management and long-term outcome.
AB - Idiopathic laryngeal spasm (ILS) is an uncommon disorder characterised by brief
episodes of stridor, occurring at any time. Subsequent outpatient ENT examination
is normal. These episodes cause considerable anxiety for both patient and
physician. Little is known about the initiating event(s) in this condition or the
long-term outcome. Using a combination of telephone and postal questionnaires
with case note review, we have reviewed a cohort of 21 patients with this
diagnosis managed by the senior author over the last 15 years. None of the 19
patients who responded were worse; 13 (68%) described improvement or complete
resolution of symptoms. ILS is difficult to classify in the spectrum of vocal
cord disorders, but appears distinct to those previously described. The condition
responds well to a conservative management approach of reassurance and
counselling.
PMID- 17033830
TI - Lymphoscintigraphy and radioguided sentinel node biopsy in oral cavity squamous
cell carcinoma: same day protocol.
AB - The routine use of a sentinel node biopsy (SNB) protocol in oral cavity squamous
cell carcinomas (SCC) has been challenged on the basis of the elevated number of
sentinel nodes (SNs) detected (>2.5) and on the multiply neck level involvement
reported in several studies. These data limit the practical application of the
protocol, because in such cases, it seems easier and safer to perform a selective
neck dissection. The aim of our study is to perform radioguided surgery 1-3 h
after lymphoscintigraphy (same day protocol) to detect the lymph nodes closest to
the tumour site. In our study, 12 patients affected by cT1-2 N0 SCC of the oral
cavity were submitted to a same day protocol of a lymphoscintigraphic examination
(1-3 h before surgery) and a radioguided SNB. We used a hand-held gamma probe and
performed an elective neck dissection on all patients. The SNs were found in all
cases with 83% localised in the ipsilateral neck in only levels I-II. The mean
number of SN detected was 2.1, with a mean pathological size of 13.8 mm measured
on pathological specimen. Metastases were found in 5/12 cases (41.6%), on levels
I, II and III and all were identified by step serial sectioning and routine H&E
staining. This study confirms the accuracy of SNB in predicting the presence of
occult metastases. This protocol is designed to detect SNs, which are almost
always on neck level I and II, thereby limiting the number of nodes examined and
the extension of the surgical approach.
PMID- 17033831
TI - Non-specific immunological determinations in Meniere's disease: any role in
clinical practice?
AB - Several studies supported the hypothesis that an autoimmune response may be a
pathogenetic factor in Meniere's disease occurrence. It has been demonstrated
that the endo-lymphatic sac has an important role in the immuno-mediated reaction
and it has also become evident that an immunological mechanism may be involved in
the development of endo-lymphatic hydrops. The present study was carried out in
order to analyse the validity of serological non-specific immune tests in
determining the possible role of immune pathology in 200 Meniere's suffering
patients. The immune activity was investigated determining the erythrocyte
sedimentation rate (ESR), the C-reactive protein levels, the rheumatoid factor,
the serum immunoglobulin levels by group, the complement levels, the lymphocyte
sub-populations, the cryoglobulines, the circulating immune complexes (CIC),
organ and non-organ auto-antibodies. Levels of Ig, ESR, C-reactive protein,
rheumatoid factor, complement fractions and cryoglobulines were either negative
or non-significant in the considered cohort of Meniere's disease suffering
patients. On the other hand, in more than half of the sample group high values of
CIC were found. Data concerning T-lymphocyte sub-population indicates a clear
increase in T-helper compared to T-cytotoxic cells, with an increase in the
CD4/CD8 ratio. The datum of particular interest concerns analysis of T-cells
activation complexes. Our present findings show that early activated T
lymphocytes change and in particular changes occur in the expression of the
interleukin-2 receptor. Moreover, it seems to be possible to correlate the
alteration of the immunological tests and the phase of the disease. Present data
showed that the immunological factor should be considered a relevant element in
most of the cases of Meniere's disease.
PMID- 17033832
TI - Skin damage occurs early in systemic lupus erythematosus and independently of
disease duration in Brazilian patients.
AB - To determine if skin damage is related to disease duration in Brazilian patients
with SLE followed in a tertiary reference center through the application of
standardized damage index (SLICC/ACR-DI). Sixty SLE patients were enrolled in
this study. Relevant data were obtained through patients' interview, physical and
laboratory examinations and review of the hospital records. The frequency and the
different types of organ damage were determined using de SLICC/ACR-DI. Statistics
were performed through chi-square and Student's t tests. Multivariate regression
was used to correlate damage with disease duration. Forty-one (68.3%) patients
presented any type of cumulative organ damage. The skin (35%), renal (23.3%) and
neuropsychiatric (18.3%) systems were the most frequently involved, followed by
peripheric vascular, ocular and cardiovascular systems. Non-Caucasoid patients
and patients with longer disease duration had a slight tendency for greater organ
damage (P = 0.05). Skin damage occurred independently of disease duration,
whereas cardiovascular (P = 0.051), peripheral vascular (P = 0.057) and pulmonary
damage (P = 0.06) had a tendency to occur more frequently in patients with longer
disease duration. In this study, 68.3% of permanent damage was observed. An
elevated frequency of skin damage was observed in this population which occurred
independently of disease duration. Non-Caucasian patients had a tendency to
present higher scores, but more studies are necessary to determine if ethnic or
economic factors are involved.
PMID- 17033833
TI - Pregnancy outcome in idiopathic inflammatory myopathy.
AB - The aim of our study was to assess the prevalence and outcome of pregnancy in
idiopathic inflammatory myopathy patients who became pregnant after the onset of
the disease. Female idiopathic inflammatory myopathy patients (173) were included
in our study. The patients' charts and clinical data were retrospectively
analyzed. One hundred and four female idiopathic inflammatory myopathy patients
had 186 pregnancies, but only nine of these patients (4 polymyositis-PM, 5
dermatomyositis-DM) became pregnant after the onset of the disease. Nine patients
with pregnancies after the disease onset had 14 gravidities. Six pregnancies
resulted in normal deliveries, two ended in prematurity, six ended in abortions
(two induced abortions). Regarding the four patients (3 PM, 1 DM) with active
disease at the time of pregnancy, two pregnancies ended in prematurity, four
ended in spontaneous abortion and one healthy baby delivered. The other five
patients (2 PM, 3 DM) with the disease in remission had uneventful pregnancies
and healthy babies were delivered. Treatment was not required during pregnancy in
case of two dermatomyositis patients with long lasting remission. New onset
dermatomyositis developed in one patient in her pregnancy's third trimester. The
mean weight of newborns in the active myositis cases was 2,193 (1,680-2,700) g;
while in patients with remission was 3,167 (2,800-3,800) g. The active maternal
disease in idiopathic inflammatory myopathy (IIM) might result intrauterin
retardation and death. Disease activity in active and new-onset cases could be
controlled by increasing the dose of corticosteroid.
PMID- 17033834
TI - Effect of dehydroepiandrosterone on cartilage and synovium of knee joints with
osteoarthritis in rabbits.
AB - The aim of this study was to investigate the effects of intra-articular injection
of dehydroepiandrosterone (DHEA) on cartilage and synovium of knee joints with
osteoarthritis (OA) in rabbits and the underlying mechanism. Forty rabbits
underwent unilateral anterior cruciate ligament transaction and were divided into
two groups. Rabbits were injected with 100 mumol/l DHEA dissolved in the
dimethylsulphoxide (DMSO) in the knee joints 5 weeks after transaction, once a
week for 5 weeks. Rabbits injected with DMSO under the same condition were served
as a control. All rabbits were killed 1 week after the last injection. The knee
joints were evaluated by gross morphology, histology, and gene expression
analysis. Gross morphologic inspection and histological evaluation showed that
the DHEA group appeared less damage in cartilage and synovium as compared with
the control. Gene expression analysis revealed that the mRNA expression of matrix
metalloproteinase-3 (MMP-3) in cartilage and synovium decreased significantly in
the DHEA group and that of tissue inhibitor of metalloproteinase-1 (TIMP-1)
increased. No significant difference of interleukin-1 beta (IL-1beta) mRNA
expression was found in the cartilage between two groups while the mRNA
expression of IL-1beta in the synovium was largely suppressed in the DHEA group.
The study suggests that DHEA plays a protective role against cartilage
degradation and synovium inflammation in rabbits with OA. This role may be
achieved through the regulation of the MMP-3, TIMP-1, and IL-1beta gene
expression in the cartilage and synovium.
PMID- 17033835
TI - Effects of balneotherapy on serum IL-1, PGE2 and LTB4 levels in fibromyalgia
patients.
AB - The purpose of this study was to investigate the clinical effects of
balneotherapy in the treatment of Fibromyalgia Syndrome (FMS) and to determine if
balneotherapy influences serum levels of inflammation markers, IL-1, PGE2 and
LTB4. 24 primary fibromyalgia female patients diagnosed according to American
College of Rheumatology criteria were included to the study. Their ages ranged
between 33 and 55 years. FMS patients were randomly assigned in two groups as,
group 1 (n = 12) and group 2 (n = 12). Group 1 received 20-min bathing, once in a
day for five days per week. Patients participated in the study for 3 weeks (total
of 15 sessions) in Denizli. Group 2 did not receive balneotherapy. FMS patients
were evaluated by tenderness measurements (tender point count and algometry),
Visual Analogue Scale, Beck's Depression Index, Fibromyalgia Impact
Questionnaire. Ten healthy women recruited group three as the controls. Serum
PGE2, LTB4 and IL1-alpha levels were measured in all three groups. The
biochemical measurements and clinical assessments were performed before and at
the end of general period of therapy. Statistically significant alterations in
algometric score, Visual Analogue score, Beck's Depression Index and PGE2 levels
(P < 0.001), numbers of tender points (P < 0.01) and Fibromyalgia Impact
Questionnaire score (P < 0.05) were found after the balneotherapy between group 1
and 2. Mean PGE2 level of FMS patients were higher compared to healthy control
group (P < 0.0001) and decreased after the treatment period, only in group 1 (P <
0.05). As in the group 2 and 3, detectable IL-1 and LTB4 measurements were
insufficient, statistical analysis was performed, only in group 1. After
balneotherapy IL-1 and LTB4 significantly decreased in group 1 (P < 0.05). In
conclusion, balneotherapy is an effective choice of treatment in patients with
FMS relieving the clinical symptoms, and possibly influencing the inflammatory
mediators.
PMID- 17033836
TI - Comment on: Schmidt MI, Duncan BB, Vigo A et al (2006) Leptin and incident type 2
diabetes: risk or protection? Diabetologia 49:2086-2096.
PMID- 17033837
TI - Common variants in HNF-1 alpha and risk of type 2 diabetes.
AB - AIMS/HYPOTHESIS: Mutations in the hepatocyte nuclear factor 1-alpha gene (HNF
1alpha, now known as the transcription factor 1 gene [TCF1]) cause the most
common monogenic form of diabetes, MODY3, but it is not known if common variants
in HNF-1a are associated with decreased transcriptional activity or phenotypes
related to type 2 diabetes, or whether they predict future type 2 diabetes.
SUBJECTS AND METHODS: We studied the effect of four common polymorphisms
(rs1920792, I27L, A98V and S487N) in and upstream of the HNF-1alpha gene on
transcriptional activity in vitro, and their possible association with type 2
diabetes and insulin secretion in vivo. RESULTS: Certain combinations of the I27L
and A98V polymorphisms in the HNF-1alpha gene showed decreased transcriptional
activity on the target promoters glucose transporter 2 (now known as solute
carrier family 2 [facilitated glucose transporter], member 2) and albumin in both
HeLa and INS-1 cells. In vivo, these polymorphisms were associated with a modest
but significant impairment in insulin secretion in response to oral glucose.
Insulin secretion deteriorated over time in individuals carrying the V allele of
the A98V polymorphism (n = 2,293; p = 0.003). In a new case-control (n = 1,511
and n = 2,225 respectively) data set, the I27L polymorphism was associated with
increased risk of type 2 diabetes, odds ratio (OR) = 1.5 (p = 0.002; multiple
logistic regression), particularly in elderly (age > 60 years) and overweight
(BMI > 25 kg/m(2)) patients (OR = 2.3, p = 0.002). CONCLUSIONS/INTERPRETATION:
This study provides in vitro and in vivo evidence that common variants in the
MODY3 gene, HNF-1alpha, influence transcriptional activity and insulin secretion
in vivo. These variants are associated with a modestly increased risk of late
onset type 2 diabetes in subsets of elderly overweight individuals.
PMID- 17033838
TI - Prostaglandin E2 regulates Foxo activity via the Akt pathway: implications for
pancreatic islet beta cell dysfunction.
AB - AIMS/HYPOTHESIS: Prostaglandin E(2) (PGE(2)) is a well-recognised inhibitor of
glucose-stimulated insulin secretion (GSIS). The aim of this study was to
investigate the signalling pathway of PGE(2) in beta cell function regulation in
HIT-T15 cells and isolated rat islets. MATERIALS AND METHODS: mRNA levels of the
prostaglandin E receptor 3 (Ptger3) were measured by real-time PCR. Western blot
analysis was used to detect changes in the levels of PTGER3, phosphorylated and
total Akt, phosphorylated and total forkhead box 'Other' (Foxo). Transient
transfection and reporter assays were used to measure Foxo transcriptional
activity. The biological significance of PGE(2) in beta cell function was
analysed using MTT, flow cytometry and GSIS assays. RESULTS: We found that
treating HIT-T15 cells with exogenous PGE(2) stimulated Ptger3 gene expression
specifically, and diminished cAMP generation. These were accompanied by the
downregulation of Akt and Foxo phosphorylation in HIT-T15 cells and isolated rat
islets. Moreover, PGE(2) upregulated basal and partially reversed constitutively
active Akt-inactivated Foxo transcriptional activity. Furthermore, GSIS was
impaired in PGE(2)-treated HIT-T15 cells and isolated islets. However, the dosage
used in the above experiments did not affect beta cell viability and apoptosis.
In addition, insulin-like growth factor 1 (IGF-1) pretreatment reversed the
effects of PGE(2), and wortmannin treatment abolished the preventive effects of
IGF-1. CONCLUSIONS/INTERPRETATION: Our observations strongly suggest that PGE(2)
can induce pancreatic beta cell dysfunction through the induction of Ptger3 gene
expression and inhibition of Akt/Foxo phosphorylation without impacting beta cell
viability. These results shed light on the mechanisms of PGE(2) actions in
pancreatic beta cell dysfunction.
PMID- 17033839
TI - Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid
induced skeletal muscle insulin resistance in vitro.
AB - AIMS/HYPOTHESIS: Stearoyl CoA desaturase 1 (SCD1) is implicated in mediating
obesity and insulin resistance. Paradoxically, SCD1 converts saturated fatty
acids, the lipid species implicated in mediating insulin resistance, to
monounsaturated fatty acids. The aim of the present study was to assess the
molecular mechanisms that implicate SCD1 in the aetiology of fatty acid-induced
insulin resistance. METHODS: SCD1 protein was transiently decreased or increased
in rat L6 skeletal muscle myotubes using SCD1 short interfering RNA (siRNA) or
liposome-mediated transfection of pcDNA3.1/Hygro-mSCD1, respectively. RESULTS:
Reducing SCD1 protein resulted in marked esterification of exogenous fatty acids
into diacylglycerol (DAG) and ceramide. Insulin-stimulated Akt activity and
phosphorylation and 2-deoxyglucose uptake were reduced with SCD1 siRNA. Exposure
of L6 myotubes to palmitate abolished insulin-stimulated glucose uptake in both
control and SCD1 siRNA myotubes. Overexpression of SCD1 resulted in
triacylglycerol esterification but attenuated ceramide and DAG accumulation and
protected myotubes from fatty acid-induced insulin resistance.
CONCLUSIONS/INTERPRETATION: SCD1 protects from cellular toxicity in L6 myotubes
by preventing excessive accumulation of bioactive lipid metabolites.
PMID- 17033841
TI - Splenogonadal fusion: a rare cause of testicular enlargement.
AB - Splenogonadal fusion is a rare congenital abnormality found in boys and girls.
There is fusion of the developing splenic anlage and the gonadal mesoderm at
approximately week 5 of intrauterine life. It commonly presents as a testicular
mass treated with an unnecessary orchidectomy. We report two cases of the
discontinuous type presenting with testicular swelling and review the literature.
PMID- 17033842
TI - Multifocal Balamuthia mandrillaris infection in a dog in Australia.
AB - A 6-year-old male golden retriever, with an 8-month history of seizures and a
clinical diagnosis of lymphoma in the central nervous system, was (at the owner's
request) euthanized after signs of respiratory distress and shock developed. Upon
postmortem examination, the diagnoses of meningoencephalitis and pneumonia were
made. A histological examination of selected tissues from both the lung and
central nervous system revealed a severe, acute, multifocal, amoebic, embolic
pneumonia and a severe, chronic, multifocal, nonsuppurative, amoebic
meningoencephalitis. Indirect immunofluorescence analysis confirmed the presence
of trophozoite and cyst stages of Balamuthia mandrillaris. This is the first
report of B. mandrillaris (which is a free-living amoeba) causing fatal,
multifocal granulomatous amoebiasis in a dog in Australia.
PMID- 17033843
TI - The role of gastrin-releasing peptide on conditioned fear: differential cortical
and amygdaloid responses in the rat.
AB - RATIONALE: Bombesin (BB), an amphibian peptide, was shown to affect the
expression of the stress response. However, the physiological role of the
mammalian counterparts of BB in mediating anxiety and fear responses remain to be
characterized. OBJECTIVE: This study examined the effects of gastrin-releasing
peptide (GRP), a mammalian analogue of BB, and its receptor antagonist,
BW2258U89, on conditioned emotional response (CER), using fear conditioning.
MATERIALS AND METHODS: The effects of these compounds on contextual and cued fear
conditioning were assessed after direct bilateral infusions into the prelimbic
(PrL) cortex, infralimbic (IL) cortex or central nucleus of the amygdala (CeA).
RESULTS: GRP (300 ng) microinjected into each of the three target nuclei
significantly reduced freezing to contextual cues. Similarly, in the cued portion
of CER, GRP administered to the IL cortex significantly reduced freezing.
Administration of BW2258U89 resulted in dose-dependent and site-specific effects.
At the IL cortex, the 50 ng dose decreased freezing to both contextual and cued
fear conditioning. At the CeA, the 300 ng dose also decreased freezing, but at
the 50 ng dose, it increased contextual freezing. At the PrL cortex, BW2258U89
did not affect freezing. CONCLUSIONS: These results illustrate that (1) GRP
system(s) can significantly affect the expression of learned fear, (2) some of
the relevant brain sites mediating these effects include the PrL, IL and the CeA,
and (3) such effects may be dependent upon whether responses were evoked by
environmental contextual fear cues or by specific auditory cues that were
explicitly paired with an aversive stimulus.
PMID- 17033844
TI - Serotonin transporter occupancy induced by paroxetine in patients with major
depression disorder: a 123I-ADAM SPECT study.
AB - RATIONALE: To assess the paroxetine-induced serotonin transporter (SERT)
occupancy (SERTocc) using in vivo (123)I-ADAM SPECT. OBJECTIVES: (123)I-ADAM
SPECT was used to investigate the SERTocc induced by paroxetine in major
depression disorder (MDD) patients, to compare the SERT availability in drug-free
MDD patients and healthy volunteers, and to study the relationship between
paroxetine plasma concentrations (Cp) and SERTocc. MATERIALS AND METHODS:
Measures of SERT availability by means of (123)I-ADAM SPECT were obtained in ten
MDD patients before and after 4- to 6-week treatment with paroxetine 20 mg/day.
(123)I-ADAM SPECT measures of SERT availability from a group of ten previously
studied age-matched healthy volunteers were used for comparison. The relationship
between percentages of SERTocc and paroxetine Cp was studied using an E (max)
model. RESULTS: Mean SERTocc values were 66.4 +/- 9.5% in midbrain, 63.0 +/- 9.6%
in thalamus, and 61.3 +/- 10.9% in striatum. No significant differences in
SERTocc were found among these three regions. No significant differences in mean
SERT availability were found in any region between drug-free MDD patients
(midbrain = 1.14 +/- 0.15; thalamus = 0.85 +/- 0.13; striatum = 0.70 +/- 0.07)
and healthy volunteers (midbrain = 1.19 +/- 0.22; thalamus = 0.96 +/- 0.14;
striatum = 0.67 +/- 0.15). The E (max) model returned a SERTocc(max) = 70.5% and
a Cp(50) = 2.7 ng/ml. CONCLUSIONS: Using (123)I-ADAM SPECT, treatment with
paroxetine 20 mg/day leads to more than 60% SERTocc on average in cerebral
regions with known high SERT density. Data from this study do not support the
existence of SERT availability differences between drug-free MDD patients and
healthy volunteers. Finally, the E (max) model is suitable for the study of
paroxetine Cp relationship to (123)I-ADAM SPECT-measured SERTocc. This approach
may be useful for pharmacokinetic-pharmacodynamic relationships in drug
development.
PMID- 17033845
TI - Hand-held gamma probe or hand-held miniature gamma camera for minimally invasive
parathyroidectomy: competition, evolution or synergy?
PMID- 17033846
TI - MIBG-SPECT/CT-angiography with 3-D reconstruction of an extra-adrenal
phaeochromocytoma with dissection of an aortic aneurysm.
PMID- 17033847
TI - Potential role of a new hand-held miniature gamma camera in performing minimally
invasive parathyroidectomy.
AB - PURPOSE: Sestamibi scans have increased the use of minimally invasive
parathyroidectomy (MIP) to treat primary hyperparathyroidism (PHPT) when caused
by a parathyroid single adenoma. The greatest concern for surgeons remains the
proper identification of pathological glands in a limited surgical field. We have
studied the usefulness of a new hand-held miniature gamma camera (MGC) when used
intraoperatively to locate parathyroid adenomas. To our knowledge this is the
first report published on this subject in the scientific literature. METHODS:
Five patients with PHPT secondary to a single adenoma, positively diagnosed by
preoperative sestamibi scans, underwent a MIP. A gamma probe for radioguided
surgery and the new hand-held MGC were used consecutively to locate the
pathological glands. This new MGC has a module composed of a high-resolution
interchangeable collimator and a CsI(Na) scintillating crystal. It has dimensions
of around 15 cmx8 cmx9 cm and weighs 1 kg. The intraoperative assay of PTH
(ioPTH) was used to confirm the complete resection of pathological tissue.
RESULTS: All cases were operated on successfully by a MIP. The ioPTH confirmed
the excision of all pathological tissues. The MGC proved its usefulness in all
patients, even in a difficult case in which the first attempt with the gamma
probe failed. In all cases it offered real-time accurate intraoperative images.
CONCLUSION: The hand-held MGC is a useful instrument in MIP for PHPT. It may be
used to complement the standard tools used to date, or may even replace them, at
least in selected cases of single adenomas.
PMID- 17033848
TI - Quantification of FDG PET studies using standardised uptake values in multi
centre trials: effects of image reconstruction, resolution and ROI definition
parameters.
AB - PURPOSE: Standardised uptake values (SUVs) depend on acquisition, reconstruction
and region of interest (ROI) parameters. SUV quantification in multi-centre
trials therefore requires standardisation of acquisition and analysis protocols.
However, standardisation is difficult owing to the use of different scanners,
image reconstruction and data analysis software. In this study we evaluated
whether SUVs, obtained at three different institutes, may be directly compared
after calibration and correction for inter-institute differences. METHODS: First,
an anthropomorphic thorax phantom containing variously sized spheres and
activities, simulating tumours, was scanned and processed in each institute to
evaluate differences in scanner calibration. Secondly, effects of image
reconstruction and ROI method on recovery coefficients were studied. Next, SUVs
were derived for tumours in 23 subjects. Of these 23 patients, four and ten were
scanned in two institutes on an HR+ PET scanner and nine were scanned in one
institute on an ECAT EXACT PET scanner. All phantom and clinical data were
reconstructed using iterative reconstruction with various iterations, with both
measured (MAC) and segmented attenuation correction (SAC) and at various image
resolutions. Activity concentrations (AC) or SUVs were derived using various ROI
isocontours. RESULTS: Phantom data revealed differences in SUV quantification of
up to 30%. After application-specific calibration, recovery coefficients obtained
in each institute were equal to within 15%. Varying the ROI isocontour value
resulted in a predictable change in SUV (or AC) for both phantom and clinical
data. Variation of image resolution resulted in a predictable change in SUV
quantification for large spheres/tumours (>5 cc) only. For smaller tumours (<2
cc), differences of up to 40% were found between high (7 mm) and low (10 mm)
resolution images. Similar differences occurred when data were reconstructed with
a small number of iterations. Finally, no significant differences between MAC and
SAC reconstructed data were observed, except for tumours near the diaphragm.
CONCLUSION: Standardisation of acquisition, reconstruction and ROI methods is
preferred for SUV quantification in multi-centre trials. Small unavoidable
differences in methodology can be accommodated by performing a phantom study to
assess inter-institute correction factors.
PMID- 17033849
TI - Multimodal fusion imaging ensemble for targeted sentinel lymph node management:
initial results of an innovative promising approach for anatomically difficult
lymphatic drainage in different tumour entities.
AB - PURPOSE: There are situations where exact identification and localisation of
sentinel lymph nodes (SLNs) are very difficult using lymphoscintigraphy, a hand
held gamma probe and vital dye, either a priori or a posteriori. We developed a
new method using a simultaneous injection of two lymphotropic agents for exact
topographical tomographic localisation and biopsy of draining SLNs. The purpose
of this prospective pilot study was to investigate the feasibility and efficacy
of this method ensemble. METHODS: Fourteen patients with different tumour
entities were enrolled. A mixture of (99m)Tc-nanocolloid and a dissolved
superparamagnetic iron oxide was injected interstitially. Dynamic, sequential
static lymphoscintigraphy and SPECT served as pathfinders. MR imaging was
performed 2 h after injection. SPECT, contrast MRI and, if necessary, CT scan
data sets were fused and evaluated with special regard to the topographical
location of SLNs. The day after injection, nine patients underwent SLN biopsy
and, in the presence of SLN metastasis, an elective lymph node dissection.
RESULTS: Twenty-five SLNs were localised in the 14 patients examined. A 100%
fusion correlation was achieved in all patients. The anatomical sites of SLNs
detected during surgery showed 100% agreement with those localised on the
multimodal fusion images. SLNs could be excised in 11/14 patients, six of whom
had nodal metastasis. CONCLUSION: Our novel approach of multimodal fusion imaging
for targeted SLN management in primary tumours with lymphatic drainage to
anatomically difficult regions enables SLN biopsy even in patients with lymphatic
drainage to obscure regions. Currently, we are testing its validity in larger
patient groups and other tumour entities.
PMID- 17033850
TI - Evaluation of iterative reconstruction (OSEM) versus filtered back-projection for
the assessment of myocardial glucose uptake and myocardial perfusion using
dynamic PET.
AB - PURPOSE: Iterative reconstruction methods based on ordered-subset expectation
maximisation (OSEM) has replaced filtered backprojection (FBP) in many clinical
settings owing to the superior image quality. Whether OSEM is as accurate as FBP
in quantitative positron emission tomography (PET) is uncertain. We compared the
accuracy of OSEM and FBP for regional myocardial (18)F-FDG uptake and (13)NH(3)
perfusion measurements in cardiac PET. METHODS: Ten healthy volunteers were
studied. Five underwent dynamic (18)F-FDG PET during hyperinsulinaemic
euglycaemic clamp, and five underwent (13)NH(3) perfusion measurement during rest
and adenosine-induced hyperaemia. Images were reconstructed using FBP and OSEM +/
an 8-mm Gaussian post-reconstruction filter. RESULTS: Filtered and unfiltered
images showed agreement between the reconstruction methods within +/-2SD in Bland
Altman plots of K (i) values. The use of a Gaussian filter resulted in a
systematic underestimation of K (i) in the filtered images of 11%. The mean
deviation between the reconstruction methods for both unfiltered and filtered
images was 1.3%. Agreement within +/-2SD between the methods was demonstrated for
perfusion rate constants up to 2.5 min(-1), corresponding to a perfusion of 3.4
ml g(-1) min(-1). The mean deviation between the two methods for unfiltered data
was 2.7%, and for filtered data, 5.3%. CONCLUSION: The (18)F-FDG uptake rate
constants showed excellent agreement between the two reconstruction methods. In
the perfusion range up to 3.4 ml g(-1) min(-1), agreement between (13)NH(3)
perfusion obtained with OSEM and FBP was acceptable. The use of OSEM for
measurement of perfusion values higher than 3.4 ml g(-1) min(-1) requires further
evaluation.
PMID- 17033851
TI - Tendons in the plantar aspect of the foot: MR imaging and anatomic correlation in
cadavers.
AB - OBJECTIVE: The purpose of this anatomic imaging study was to illustrate the
normal complex anatomy of tendons of the plantar aspect of the ankle and foot
using magnetic resonance (MR) imaging with anatomic correlation in cadavers.
DESIGN: Seven fresh cadaveric feet (obtained and used according to institutional
guidelines, with informed consent from relatives of the deceased) were studied
with intermediate-weighted fast-spin-echo MR imaging. For anatomic analysis,
cadaveric specimens were sectioned in 3-mm-thick slices in the coronal and axial
planes that approximated the sections acquired at MR imaging. RESULTS: The entire
courses of the tendons into the plantar aspect of the foot were analyzed. The
tibialis posterior tendon has a complex distal insertion. The insertions in the
navicular, second, and third cuneiforms bones were identify in all cases using
axial and coronal planes. A tendinous connection between the flexor hallucis
longus and the flexor digitorum longus tendons was identified in five of our
specimens (71%). The coronal plane provided the best evaluation. The peroneus
longus tendon changes its direction at three points then obliquely crosses the
sole and inserts in the base of the first metatarsal bone and the plantar aspect
of the first cuneiform. CONCLUSIONS: MR imaging provides detailed information
about the anatomy of tendons in the plantar aspect of the ankle and foot. It
allows analysis of their insertions and the intertendinous connection between the
flexor hallucis longus and the flexor digitorum longus tendons.
PMID- 17033852
TI - Ultrasound detects rapid progression of erosive disease in early rheumatoid
arthritis: a prospective longitudinal study.
AB - OBJECTIVE: To evaluate and compare sequential ultrasound exams (US) with power
Doppler (PD) to radiography for the detection of synovitis and erosions in
patients with early RA. METHODS: Radiographs and US with PD of the hands and feet
were performed at baseline and 6+/- 2 months afterwards in 21 early RA patients.
Their mean (range) age was 42.6 (21-81) years and the female/male ratio was 4:3;
mean disease duration was 9 (1-28) months. Joints assessed were bilateral 2nd and
5th MCPs, 5th MTPs and the most swollen PIP in each hand, for a total of eight
joints per patient. Radiographs (PA, lateral and pronated oblique) were read for
erosions using the method of Sharp/van der Heijde. On US, erosions were defined
as cortical defects greater than 2 mm in diameter with an irregular floor.
Synovitis was rated as +1 (increase in joint fluid without synovial hyperemia),
+2 (mild blood flow), +3 (moderate blood flow), and +4 (severe blood flow). Two
blinded trained assessors read all images. RESULTS: US detected 15 erosions in 10
patients at baseline and 31 erosions in 12 patients on follow-up; radiographs
could detect only one erosion at baseline and five erosions in three patients on
follow-up. PD detected synovitis in all patients at baseline and on follow-up. Of
the joints found to have synovitis, 64% were identified as such at baseline and
38% on follow-up. CONCLUSIONS: Sequential US can determine disease progression in
patients with early RA. Such data may allow the clinician to treat RA patients
earlier in the hope of preventing joint damage.
PMID- 17033853
TI - Comment regarding "Is anterior release effective to increase flexibility in
idiopathic thoracic scoliosis? Assessment by traction films" (A. Hempfing et
al.).
PMID- 17033854
TI - Is anterior release effective to increase flexibility in idiopathic thoracic
scoliosis? Assessment by traction films.
AB - With the advent of thoracoscopy, anterior release procedures in adolescent
idiopathic scoliosis (AIS) have come into more frequent use, however, the
indication criteria for an anterior release in thoracic AIS are still
controversial in the literature. To date, few studies have assessed the influence
on spinal flexibility and no study has so far been able to show a beneficial
effect on the correction rate as compared to a single posterior procedure. The
objective of this study was to evaluate the influence of thoracic disc excision
on coronal spinal flexibility. Six patients (5 females, 1 male) with AIS and a
mean age of 15.6 years (range 13-20 years) underwent an open anterior thoracic
release prior to posterior instrumentation. Cotrel dynamic traction along with
radiographs of the whole spine including traction films were conducted pre- and
postoperatively and were evaluated retrospectively. The mean preoperative
thoracic curve was 89.7 degrees +/- 15.4 degrees (range 65 degrees-110 degrees).
The flexibility rate in Cotrel traction was 22.8 +/- 8.1%. After performance of
the anterior release the thoracic curve showed a mean increase of coronal
correction by 5.5 degrees +/- 5.0 degrees as assessed by traction radiographs.
The flexibility index changed by 6.2 +/- 5.6%. After posterior instrumentation
the thoracic curve was corrected to a mean of 36.5 degrees +/- 10.1 degrees
(correction rate 59.6%). Disc excision in idiopathic thoracic scoliosis only
slightly increased spinal flexibility as assessed by traction films. In our view
a posterior release with osteotomy of the concave ribs (concave thoracoplasty,
CTP) is more effective in increasing spinal flexibility. According to our
clinical experience, an anterior release prior to posterior instrumentation in
AIS should only be considered in hyperkyphosis, coronal imbalance or massive
curves.
PMID- 17033855
TI - Presence of white bile in malignant biliary obstruction is associated with poor
prognosis: personal preliminary observations.
AB - OBJECTIVE: The chemical composition and clinical significance of white bile in
patients with malignant obstructive jaundice were evaluated in a prospective
study. MATERIALS AND METHODS: 115 consecutive patients with inoperable malignant
biliary obstruction underwent endoscopic placement of 10 Fr straight, plastic
biliary stents, Amsterdam-type. Bile was aspirated during the endoscopic
procedure and a blood sample was taken. Patients were divided into two groups:
those with white bile and those with yellow bile. The groups were compared for
decremental fall in bilirubin, cholangitis after stent insertion, and survival.
RESULTS: Thirty-five patients (15 men, 20 women; mean age 54 years) underwent
endoscopic drainage for malignant obstruction (29 hilar, 6 distal bile duct).
Eighteen patients had white bile. Refractory jaundice (p > -0.025) was seen in
nine (50%) patients with white bile compared with three (17.6%) patients with
yellow bile; mean difference -42.2 (95% CI [-62.4, -22.0]) and -45.7 (95% CI [
72.0, -19.4]), respectively. The bilirubin (0.49 mg/L) and bile acid (14.6
mmol/L) concentrations in white bile were significantly less than bilirubin (41.9
mg/L) and bile acid (62.2 mmol/L) concentrations in yellow/black bile.
Cholangitis developed in 66.6% of patients with white bile compared with 35% of
those with yellow/black bile (OR 3.67: 95% CI [0.74, 19.25]). Kaplan-Meier curves
showed that median survival was shorter in patients with white bile (36 [23-60]
vs 75 [35-220] days) (p = 0.004, log rank test), which was significant even after
adjusting for potential confounders with Cox proportional hazards regression.
CONCLUSION: White bile is largely devoid of bilirubin and bile acids. The
presence of white bile was associated with significantly worse survival in
patients with malignant biliary obstruction.
PMID- 17033857
TI - Use of a home water filter in the reduction of trihalomethanes and total organic
halogen in tap water: forty-one samples from Osaka City and surrounding cities of
Japan in 1999, 2000, and 2004.
PMID- 17033856
TI - Microbial communities in the world's largest acidic volcanic lake, Kawah Ijen in
Indonesia, and in the Banyupahit river originating from it.
AB - A first study was made on the microbial community composition of the Indonesian
crater lake Kawah Ijen (pH < 0.3) and the Banyupahit-Banyuputih river (pH 0.4
3.5) originating from it. Culture-independent, rRNA gene-based denaturing
gradient gel electrophoresis was used to profile microbial communities in this
natural and ancient, extremely acidic environment. Similarity in community
profiles of the different sampling locations was low, indicating heterogeneity in
community composition. Archaea were present at all sampling locations; archaeal
diversity was low at the most acidic locations and increased at pH >2.6. Bacteria
were not detected in the water column of the crater lake, but were found at all
locations along the acidic river. Bacterial diversity increased with increasing
pH. Eukarya were only present at pH >2.6. Retrieved rRNA gene sequences of
Bacteria and Archaea were not closely related to known acidophilic species. It is
concluded that tolerance to extreme acidity in this system is developed most
extensively among Archaea. The acidity gradient of the Banyupahit-Banyuputih
river has a clear effect on microbial community composition and biodiversity.
PMID- 17033858
TI - Serum levels of volatile organic compounds in patients with sick building
syndrome.
PMID- 17033859
TI - Smoking and alcohol use in asbestos abatement workers.
PMID- 17033860
TI - Dechlorination of DDT by electrocatalytic hydrogenolysis.
PMID- 17033861
TI - Mercury and organomercurial resistance in Rhodotorula rubra: activation of
glutathione reductase.
PMID- 17033862
TI - Use of the Nile monitor, Varanus niloticus L (Reptilia: Varanidae), as a
bioindicator of organochlorine pollution in African wetlands.
PMID- 17033863
TI - Seasonal variation of microcystin concentration in Lake Chaohu, a shallow
subtropical lake in the People's Republic of China.
PMID- 17033864
TI - Alternative water management for controlling simetryn and thiobencarb runoff from
paddy fields.
PMID- 17033865
TI - Monitoring phenolic compounds during biological treatment of Kraft pulp mill
effluent using bacterial biosensors.
PMID- 17033866
TI - Variation in pesticide concentrations during composting of food waste and fowl
droppings.
PMID- 17033867
TI - Pesticide residues in commercial egg samples in Sao Paulo City, Brazil, 2003
2005.
PMID- 17033868
TI - Polychlorinated dibenzo-p-dioxins and dibenzofurans in mussels and Gammarus spp.
from Dongting Lake in People's Republic of China.
PMID- 17033869
TI - Accumulation of phthalic acid esters in water spinach (Ipomoea aquatica) and in
paddy soil.
PMID- 17033870
TI - Comparison of trace metals concentration in PM10 of different locations of
Lucknow City, India.
PMID- 17033871
TI - Dominance of algae in Ganga water polluted through fly-ash leaching: metal
bioaccumulation potential of selected algal species.
PMID- 17033872
TI - EDTA influences time and concentration dependent cadmium uptake characteristics
of Indian mustard.
PMID- 17033873
TI - Heavy metals in urban roadside plants from Amman, Jordan.
PMID- 17033874
TI - Organotin species in fish and bivalves samples collected from the Egyptian
Mediterranean coast of Alexandria, Egypt.
PMID- 17033875
TI - Heavy metals in water and surface sediments in Winam Gulf of Lake Victoria,
Kenya.
PMID- 17033876
TI - Uptake of heavy metals by a ciliate, Tachysoma pellionella, isolated from
industrial effluents and its potential use in bioremediation of toxic wastewater.
PMID- 17033877
TI - Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte
chemotactic protein 1 and 3.
AB - Acyclic nucleoside phosphonates are potent antiviral agents effective against
replication of DNA viruses and retroviruses including human immunodeficiency
virus (HIV). In addition to their antimetabolic mode of antiviral action, acyclic
nucleoside phosphonates also possess immunomodulatory properties. We have shown
recently that a number of them stimulate secretion of cytokines including
chemokines RANTES/CCL5 ("regulated upon activation, normal T cell expressed and
secreted") and MIP-1 alpha/CCL3 (macrophage inflammatory protein-1 alpha) that
may inhibit entry of HIV in cells. In present experiments we analyzed effects of
acyclic nucleoside phosphonates on gene expression of other members of the beta
family of chemokines, monocyte chemotactic proteins (MCPs), which have also been
implicated in the control of HIV infection. The following compounds differing at
the type of heterocyclic base, i.e. adenine (A), or 2,6-diaminopurine (DAP), at
the 6-amino group of the base, and at the N ( 9 )-side chain represented by 9-[2
(phosphonomethoxy)ethyl] (PME) and 9-[2-(phosphonomethoxy)propyl] (PMP) moieties
were included in the study: (1) (R)-PMPA, ie. tenofovir, (2) N ( 6 )-cyclopropyl
(R)-PMPDAP, (3) N ( 6 )-cyclopentyl-(R)-PMPDAP, (4) N ( 6 )-dimethylaminoethyl
(R)-PMPDAP, (5) N ( 6 )-cyclopentyl-PMEDAP, (6) N ( 6 )-isobutyl-PMEDAP, (7) N (
6 ) -cyclohexylmetyl-PMEDAP, and (8) N ( 6 ) -cyclooctyl-PMEDAP. These compounds
are able to activate production of MCP-1 and MCP-3, and none of them influences
gene expression of MCP-2, and MCP-5. Enhancement of monocyte chemotactic protein
expression was found to be mediated by transcriptional factor nuclear factor
kappaB (NF-kappaB).
PMID- 17033878
TI - Age and gender do not influence the ability to detect respiration by
photoplethysmography.
AB - OBJECTIVE: The non-invasive technique photoplethysmography (PPG) can detect
changes in blood volume and perfusion in a tissue. Respiration causes variations
in the peripheral circulation, making it possible to monitor breaths using an
optical sensor attached to the skin. The respiratory-synchronous part of the PPG
signal (PPGr) has been used to monitor respiration during anaesthesia, and in
postoperative and neonatal care. Studies addressing possible differences in PPGr
signal characteristics depending on gender or age are lacking. METHODS: We
studied three groups of 16 healthy subjects each during normal breathing; young
males, old males and young females, and calculated the concordance between PPGr,
derived from a reflection mode PPG sensor on the forearm, and a reference CO(2
)signal. The concordance was quantified by using a squared coherence analysis.
Time delay between the two signals was calculated. In this process, we compared
three different methods for calculating time delay. RESULTS: Coherence values
>or=0.92 were seen for all three groups without any significant differences
depending on age or gender (p = 0.67). Comparison between the three different
methods for calculating time delay showed a correlation r = 0.93. CONCLUSIONS:
These results demonstrate clinically important information implying the
possibility to register qualitative PPGr signals for respiration monitoring,
regardless of age and gender.
PMID- 17033879
TI - Research in medical education: balancing service and science.
AB - Since the latter part of the 1990's, the English-speaking medical education
community has been engaged in a debate concerning the types of research that
should have priority. To shed light on this debate and to better understand its
implications for the practice of research, 23 semi-structured interviews were
conducted with "influential figures" from the community. The results were
analyzed using the concept of "field" developed by the sociologist Pierre
Bourdieu. The results reveal that a large majority of these influential figures
believe that research in medical education continues to be of insufficient
quality despite the progress that has taken place over the past 2 decades.
According to this group, studies tend to be both redundant and opportunistic, and
researchers tend to have limited understanding of both theory and methodological
practice from the social sciences. Three factors were identified by the
participants to explain the current problems in research: the working conditions
of researchers, budgetary restraints in financing research in medical education,
and the conception of research in the medical environment. Two principal means
for improving research are presented: intensifying collaboration between PhD's
and clinicians, and encouraging the diversification of perspectives brought to
bear on research in medical education.
PMID- 17033880
TI - Biological control of the size and reactivity of catalytic Pd(0) produced by
Shewanella oneidensis.
AB - The interaction between Shewanella oneidensis MR-1 and the soluble metal Pd(II)
during the reductive precipitation of Pd(0) determined the size and properties of
the precipitated Pd(0) nanoparticles. Assessment of cell viability indicated that
the bioreduction of Pd(II) was a detoxification mechanism depending on the Pd(II)
concentration and on the presence and properties of the electron donor. The
addition of H(2) in the headspace allowed S. oneidensis to resist the toxic
effects of Pd(II). Interestingly, 25 mM formate was a less effective electron
donor for bioreductive detoxification of Pd(II), since there was a 2 log
reduction of culturable cells and a 20% decrease of viable cells within 60 min,
followed by a slow recovery. When the ratio of Pd:cell dry weight (CDW) was below
5:2 at a concentration of 50 mg l(-1) Pd(II), most of the cells remained viable.
These viable cells precipitated Pd(0) crystals over a relatively larger bacterial
surface area and had a particle area that was up to 100 times smaller when
compared to Pd(0) crystals formed on non-viable biomass (Pd:CDW ratio of 5:2).
The relatively large and densely covering Pd(0) crystals on non-viable biomass
exhibited high catalytic reactivity towards hydrophobic molecules such as
polychlorinated biphenyls, while the smaller and more dispersed nanocrystals on a
viable bacterial carrier exhibited high catalytic reactivity towards the
reductive degradation of the anionic pollutant perchlorate.
PMID- 17033881
TI - Nitrogen transformations in stratified aquatic microbial ecosystems.
AB - New analytical methods such as advanced molecular techniques and microsensors
have resulted in new insights about how nitrogen transformations in stratified
microbial systems such as sediments and biofilms are regulated at a microm-mm
scale. A large and ever-expanding knowledge base about nitrogen fixation,
nitrification, denitrification, and dissimilatory reduction of nitrate to
ammonium, and about the microorganisms performing the processes, has been
produced by use of these techniques. During the last decade the discovery of
anammmox bacteria and migrating, nitrate accumulating bacteria performing
dissimilatory reduction of nitrate to ammonium have given new dimensions to the
understanding of nitrogen cycling in nature, and the occurrence of these
organisms and processes in stratified microbial communities will be described in
detail.
PMID- 17033882
TI - Alcoholic fermentation of carbon sources in biomass hydrolysates by Saccharomyces
cerevisiae: current status.
AB - Fuel ethanol production from plant biomass hydrolysates by Saccharomyces
cerevisiae is of great economic and environmental significance. This paper
reviews the current status with respect to alcoholic fermentation of the main
plant biomass-derived monosaccharides by this yeast. Wild-type S. cerevisiae
strains readily ferment glucose, mannose and fructose via the Embden-Meyerhof
pathway of glycolysis, while galactose is fermented via the Leloir pathway.
Construction of yeast strains that efficiently convert other potentially
fermentable substrates in plant biomass hydrolysates into ethanol is a major
challenge in metabolic engineering. The most abundant of these compounds is
xylose. Recent metabolic and evolutionary engineering studies on S. cerevisiae
strains that express a fungal xylose isomerase have enabled the rapid and
efficient anaerobic fermentation of this pentose. L: -Arabinose fermentation,
based on the expression of a prokaryotic pathway in S. cerevisiae, has also been
established, but needs further optimization before it can be considered for
industrial implementation. In addition to these already investigated strategies,
possible approaches for metabolic engineering of galacturonic acid and rhamnose
fermentation by S. cerevisiae are discussed. An emerging and major challenge is
to achieve the rapid transition from proof-of-principle experiments under
'academic' conditions (synthetic media, single substrates or simple substrate
mixtures, absence of toxic inhibitors) towards efficient conversion of complex
industrial substrate mixtures that contain synergistically acting inhibitors.
PMID- 17033883
TI - The value of autonomy in medical ethics.
AB - This articles assesses the arguments that bioethicists have presented for the
view that patients' autonomy has value over and beyond its instrumental value in
promoting the patients' wellbeing. It argues that this view should be rejected
and concludes that patients' autonomy should be taken to have only instrumental
value in medicine.
PMID- 17033884
TI - Primary splenic marginal zone lymphoma with bladder metastases mimicking
interstitial cystitis.
AB - We report the case of a 76-year-old patient with a past medical history of low
grade chronic lymphocytic leukaemia who presented with severe chronic bladder
symptoms attributed to interstitial cystitis. She underwent cystectomy and ileal
conduit formation after the failure of all conventional treatment. Bladder
histopathology revealed primary splenic marginal zone lymphoma. Literature review
shows the rarity of such non-hematopoietic visceral metastases. This may
represent the first reported splenic marginal zone lymphoma with bladder
involvement and highlights the clinical and histological similarities with
interstitial cystitis.
PMID- 17033885
TI - Giant unilateral abdominoscrotal hydrocele in an adult: case report.
AB - Abdominoscrotal hydrocele (ASH) is an apparently highly uncommon clinical entity
especially in childhood. While hydrocele is among the commonest inguinal anomaly
in adult, its extreme form ASH is infrequently reported form. ASH consists of two
large sacs, both abdominal and scrotal, connecting with the inguinal canal.
Surgical correction is mandatory. We present a 34-year-old man with giant ASH. He
was treated with excision of hydrocele sac through an inguinal approach.
PMID- 17033886
TI - Capillary haemangioma of verumontanum: case report and review of the literature.
AB - A case of 24-year-old male patient with persisting microscopic haematuria is
described. The endoscopic diagnosis revealed polyp lesion protruding from the
origin of verumontanum. The histopathologic examination showed capillary
haemangioma with fibroepitel component containing no prostatic glandular
structure. The literature was reviewed, the histogenesis and nomenclature was
discussed.
PMID- 17033887
TI - Renal angiomyolipoma with malignant transformation, simultaneous occurrence with
malignity and other complex clinical situations.
AB - Renal angiomyolipoma is a benign kidney tumor, which is characterized by the
presence of mature or immature fat tissue, thick-walled blood vessels, and smooth
muscles. However, there is a rare possibility of transformation to a malignancy.
This transformation could be toward sarcoma. And also angiomyolipoma could be
associated with renal adenocarcinoma in the same kidney. The aim of this study is
to show the association of angiomyolipoma with complex clinical situations such
as malign transformation, simultaneous occurrence with adenocarcinoma, bilateral
tumors with tuberous sclerosis or Wunderlich Syndrome. Findings of clinical
presentation, pathological evaluation, urography, ultrasonography, and
computerized tomography of 19 patients who were diagnosed angiomyolipoma in our
clinic during 1994-2003 were examined retrospectively. Our records indicated that
radical nephrectomy was performed in three cases of angiomyolipoma in which the
differential diagnosis from adenocarcinoma could not be made and in another case
of angiomyolipoma, which was associated with adenocarcinoma. Simple nephrectomy
was performed in four symptomatic angiomyolipoma cases with tumor size larger
than 4 cm and partial nephrectomy in another case. In one case, renal
angiomyolipoma was associated with adenocarcinoma in the same kidney. In one
case, post-operative recurrence of angiomyolipoma developed 7 months after
nephrectomy. This patient was diagnosed low-grade leiomyosarcoma. Angiomyolipoma
is regarded as a benign tumor of the kidney; however, it may also show aggressive
behaviors and rarely transform to sarcoma. It may also exist in the same kidney
along with adenocarcinoma or sarcoma.
PMID- 17033888
TI - Digital subtraction angiography and computer assisted image analysis for the
evaluation of the antiangiogenetic effect of ionizing radiation on tumor
angiogenesis.
AB - PURPOSE: The aim of the present study was to evaluate and quantify the
antiangiogenetic effect of ionizing radiation on tumor angiogenesis using digital
subtraction angiography (DSA) in conjunction with computer assisted image
analysis (CAIA). METHODS: Walker 256 carcinosarcoma was inoculated in both glutei
of 12 Wistar rats. When the tumors reached a diameter of 1.5 cm, local
irradiation of the right gluteus was performed. The left gluteus of each animal
served as a control. After 24 hours of irradiation, angiography was performed,
and images where digitized and subsequently processed. The effect of irradiation
was observed both in big and small vessels (smaller or greater than 200 microm).
RESULTS: Irradiated areas of both small and big vessels showed a statistically
significant reduction in both total vessel area and length. Small vessels showed
a greater trend toward suppression by irradiation (not statistically
significant). CONCLUSION: Irradiation had a deleterious effect in both macro- and
micro-blood supply of a tumor. The use of CAIA enhanced the efficacy of DSA and
enabled the in vivo identification of the effect of irradiation on various
caliber vessels as well as the ratios of total length and total area of small and
big vessels.
PMID- 17033889
TI - Window technique on circumcision.
AB - OBJECTIVE: To remove the preputium by using a simple, quick and safe method
without damaging glans, frenulum and urethra as well as with a good cosmetic
result. PATIENTS AND METHODS: The procedure, remind the guillotine technique at
first, but completely different from it. Basically, a long haemostat is applied
onto preputium and skin and subdermal tissue were incised; a small window is
opened at dorsal of preputial mucosa and it is excised, while observing glans and
frenulum. RESULTS: The circumcisions were performed in a quick, safe and pretty
bloodless way. There was no case with glans amputation, frenulum short cut or
urethral damage, even if a clamp includes the foreskin with a part of glans or
excess frenulum unnoticedly. CONCLUSION: This technique is simple, quick,
relatively bloodless operation with cosmetically good result. Morever it is quite
safe against to amputation of glans, frenular short cut or urethral fistula
formation.
PMID- 17033890
TI - Maintenance DNA methyltransferase (Met1) and silencing of CpG-methylated foreign
DNA in Volvox carteri.
AB - DNA methylation plays an important role in the gene-silencing network of higher
eukaryotes. We have analyzed the 21.5-kb maintenance methyltransferase (M-MTase)
gene, met1, of the multicellular green alga Volvox carteri. The met1 transcript
was detected only during the period when DNA replication and cell division are
taking place. It encodes a 238 kDa protein containing eight C-terminal activity
domains typical of M-MTases, plus upstream DNA-binding domains including the
ProDom domain PD003757, which experimental analyses in animal systems have
indicated is required for targeting the enzyme to DNA-replication foci. Several
insertions of unknown function make Volvox Met1 the largest known member of the
Met1/Dnmt1 family. Here we also show that several endogenous transposon families
are CpG-methylated in Volvox, which we think causes them to be inactive. This
view is supported by the observation that an in vitro CpG-methylated gene
introduced into Volvox was maintained in the methylated and silent state over
>100 generations. Thus, we believe that Met1 recognizes and perpetuates the in
vitro methylation signal, and that the silencing machinery is then able to
transduce such a methylation-only signal into a stable heterochromatic (and
silent) state.
PMID- 17033891
TI - Functional status in the elderly with insomnia.
AB - BACKGROUND: Insomnia causes psychological distress in the elderly. Besides
primary insomnia (PI), illness, medications and psychosocial factors contribute
to development of sleep disorders. Although elderly insomniacs usually complain
of poorer daytime functioning, it is unknown whether the disorder affects
capacity to carry out activities. OBJECTIVE: To assess the relationship in the
elderly between PI, level of physical functioning, depression and anxiety
symptoms, state of psychological well-being and consumption of
psychopharmaceuticals. DESIGN: Cross-sectional, observational study. SETTING:
Populational. SUBJECTS: About 424 non-institutionalized elderly patients.
METHODS: Subjects were interviewed at public Health Centres or at home. They were
considered to have PI if DSM-IV criteria were met. The remaining variables
measured were: depression and anxiety symptoms (The Goldberg's Depression and
Anxiety Scale), cognitive state (Short Portable Mental Status Questionnaire),
physical functioning (The Katz Index and the Instrumental Activities of Daily
Living Scale), life satisfaction (The Philadelphia Geriatric Center Morale
Scale), health problems, consumption of pharmaceuticals and sociodemographic
variables. RESULTS: About 34.2% of the elderly admitted to having problems with
sleep, but only 20.3% (CI: 95%: 16.5-24.1) fulfilled the criteria for PI. The
existence of an anxiety disorder, a score below the 50th percentile on The
Philadelphia Geriatric Center Morale Scale (lower life satisfaction) and
consumption of psychopharmaceuticals were variables associated with insomnia.
Amongst the most common illnesses reported, only diabetes appeared with
significantly higher frequency in the elderly with insomnia (24.4% vs. 14.7%) (p
< 0.05). No statistically significant association was found between insomnia and
level of dependence in carrying out basic or instrumental activities.
CONCLUSIONS: Approximately one fifth of the non-institutionalized elderly meet
the criteria for PI. Those affected present a poorer state of psychological and
social well-being, although level of autonomy for conducting basic and
instrumental activities does not appear to be modified by the disorder. The
existence of an anxiety disorder, low life satisfaction and consumption of
psychopharmaceuticals constitute variables associated with PI in the population
we studied.
PMID- 17033892
TI - Personality traits and health-related quality of life in patients with mood and
anxiety disorders.
AB - BACKGROUND: Health-related quality of life (HRQL) is an accepted outcome measure
in patients with mood and anxiety disorders. Yet, surprisingly little attention
has been paid to the determinants. In this paper we test the hypothesis that it
is associated with personality traits while controlling for mental disorders.
METHODS: A large sample of outpatients (n = 640) with mood and anxiety disorders
was studied. The empirically supported five factor model of normal personality
traits was assessed using the NEO-FFI and includes: neuroticism, extraversion,
openness to experience, agreeableness, and conscientiousness. Mental disorders
were assessed with the CIDI, and HRQL with the SF-36. RESULTS: Regression
analyses revealed that the NEO-FFI scores, with the exception of
conscientiousness, were significantly associated with SF-36 subscales and summary
scores, independently from the mental disorders. The percentage of explained
variance due to the personality traits was highest for the subscales Vitality
(10.0%), Mental Health (13.3%) and the Mental Health Summary Score (9.5%).
Furthermore, specific personality traits were related to specific SF-36
subscales. CONCLUSIONS: A low HRQL of patients with mood or anxiety disorders is
not only determined by the disease or the current health but is also shaped by
personality traits that are relatively stable throughout an individual's life
time.
PMID- 17033894
TI - What does quality of life mean to older frail and non-frail community-dwelling
adults in the Netherlands?
AB - Quality of life is a commonly used but seldom defined concept and there is no
consensus on how to define it. The aim of this study was to explore the meaning
of quality of life to older frail and non-frail persons living in the community.
Qualitative interviews were conducted with 25 older men and women. The audio
taped interviews were transcribed and coded for content and analyzed using the
grounded-theory approach. Five themes emerged: (physical) health, psychological
well-being, social contacts, activities, and home and neighborhood. Factors that
influenced quality of life were having good medical care, finances and a car.
Respondents compared themselves mostly to others whose situation was worse than
their own, which resulted in a satisfactory perceived quality of life. However,
the priorities of the domains of quality of life were observed to change.
Moreover, the health of the frail limited the amount and scope of activities that
they performed. This led to a lower quality of life perceived by the frail
compared to the non-frail.
PMID- 17033893
TI - Health-related quality of life after laparoscopically assisted vaginal
hysterectomy: is uterine weight a major factor?
AB - OBJECTIVE: To assess uterine size, symptom severity, and hemoglobin level as
determinants of health-related quality of life (HRQOL) in women subsequently
undergoing laparoscopically assisted vaginal hysterectomy (LAVH). METHODS: Sixty
one consecutive women with uterine leiomyoma or adenomyosis undergoing LAVH were
studied using a prospective cohort design. The Chinese version of the Uterine
Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire was assessed
preoperatively. The Taiwan brief version of the World Health Organization Quality
of Life (WHOQOL-BREF) questionnaire and a self-assessment of the perceived health
status were assessed preoperatively and 1 day, 1 week, 12 weeks, and 18 months
postoperatively. RESULTS: Women with a greater uterine weight did not report a
greater severity of symptoms than those with lower uterine weight. Women with
more severe symptoms had lower preoperative hemoglobin levels and were usually
younger. Their perceived health status and their scores in physical domain of
WHOQOL-BREF were also significantly lower, indicating a poorer HRQOL. The mixed
effects model found that a normal (higher) baseline hemoglobin level and a
greater symptom severity were associated with a significant improvement of HRQOL
in the physical domain of WHOQOL-BREF following LAVH. CONCLUSIONS: Preoperative
symptom severity, but not uterine weight, was associated with long-term
improvement in HRQOL after LAVH. Women with severe symptoms could be considered
for LAVH before development of anemia.
PMID- 17033895
TI - Are factors associated with subjective quality of life in people with severe
mental illness consistent over time?--A 6-year follow-up study.
AB - OBJECTIVE: To investigate the cross-sectional relationship between subjective
quality of life and sociodemographic clinical and social factors over three
points of assessment during a 6-year follow-up, and to investigate longitudinal
predictors of subjective quality of life. METHOD: We investigated a sample of
people with severe mental illness (n = 92), mainly with a psychosis diagnosis, at
baseline and at an 18-month and 6-year follow-up. Measures included the
Lancashire quality of life profile, Manchester short assessment of quality of
life, Symptom Check List 90, Camberwell Assessment of Needs and the Interview
Schedule for Social Interaction. RESULTS: Cross-sectionally subjective quality of
life was associated to self-reported symptoms, social network and unmet needs.
However, these determinants varied in importance between points of assessment.
Longitudinal predictors of subjective quality of life were changes in self
reported symptoms and social network. CONCLUSION: There was a rather consistent
set of determinants of subjective quality of life over time. Social network seems
to be an important factor with relevance for improvements in subjective quality
of life, however largely overlooked in earlier studies within the field.
PMID- 17033896
TI - Recovered? Association between self-perceived recovery and the SF-36 after minor
musculoskeletal injuries.
AB - OBJECTIVE: Recovery after minor musculoskeletal injuries is often
disproportionately protracted. Our aim was to relate Short Form-36 (SF-36), to
self-perceived recovery assessed with the question" Do you feel recovered". We
hypothesized that restitution of physical factors would be reported at least as
often as improvement of symptoms or impairments and that social and mental
factors would dominate over physical as determinants for recovery. We followed
318 patients with minor traffic-related injuries for up to 6 months. RESULTS: For
all SF-36 subscores more than 60% of the recovered patients had returned to their
pre-injury levels. The subscores with the highest proportions (> 80%) were all
mainly reflecting disability. For no subscore, however, was the proportion 100%.
Normalizations in the SF-36 subscores for "Bodily Pain" (BP) (Odds Ratio, OR =
7.2), "Role limitations due to physical function" (OR = 5.3) were associated with
self-perceived recovery. CONCLUSION: Abolition of pain appears to be paramount
for the self-perceived recovery, but it is neither a sufficient nor a necessary
prerequisite. Contrary to our expectation, physical aspects of functional health
status were more strongly associated with recovery than were emotional or social
aspects.
PMID- 17033897
TI - Negative mood and quality of life in patients with asthma.
PMID- 17033898
TI - Black-white differences in health-related quality of life among older adults.
AB - Very little information exists on racial differences in quality of life among
older adults. In this paper, we examine black-white differences in health-related
quality of life (HRQOL) and identify factors that may account for these
differences. The participants were 5,986 community-dwelling persons age 65+ (62%
black at baseline) from the Chicago Health and Aging Project. Poor HRQOL was
defined as having 14 or more self-reported physically or mentally unhealthy days
over the past 30 days. A higher proportion of blacks (11.0%) than whites (9.7%)
reported poor HRQOL. After adjusting for age and sex, blacks had increased odds
of reporting poor HRQOL compared with whites (odds ratio [OR] = 1.72; 95% CI:
1.50-1.98). The black-white differences in HRQOL tended to increase with age (p <
0.05) and were greater among females (p < 0.05). Lifetime socioeconomic status,
summary measures of medical conditions, and cognitive function accounted for most
of the black-white difference (OR = 1.06; 95% CI: 0.89-1.27). Our results suggest
that racial differences in HRQOL are associated with the combined effects of
social disadvantage, poor physical health, and lower cognitive function.
PMID- 17033899
TI - Quality of life of nasopharyngeal carcinoma survivors in Mainland China.
AB - The aim of this study is to evaluate the quality of life (QoL) of nasopharyngeal
carcinoma (NPC) survivors. 192 NPC survivors treated in 1999 and 2000 were
enrolled in this study. Median follow up was 3.6 years (range 2.4-4.6 years). The
Chinese SF-36 questionnaire and a self-reported symptom checklist consisting of
14 items were completed at clinics. Sociodemographic factors and clinical
information were also collected. Most functional domains of the Chinese SF-36
were significantly worse in NPC survivors compared to the normal population.
Xerostomia, hearing loss, hypomnesia, dysphagia, and trismus were frequently
reported symptoms. Sociodemographic variables including gender, age, dialect,
educational level, monthly income, economic status, and number of comorbidities
were univariate predictors of different SF-36 domains and symptoms. Patients with
earlier T and N stage, irradiated by linear accelerator, with lower dose and
weekly dose to nasopharynx and neck, and those who had anterior nasal radiation
field reported better QoL. Multiple stepwise regression analysis showed that the
number of comorbidities, monthly income, age, and T stage were independent
factors affecting global QoL. We concluded that NPC survivors had worse QoL than
the normal population and improving radiotherapy might increase physical and
functional domain of QoL.
PMID- 17033900
TI - Once-daily sublingual allergen-specific immunotherapy improves quality of life in
patients with grass pollen-induced allergic rhinoconjunctivitis: a double-blind,
randomised study.
AB - The effect of sublingual immunotherapy on quality of life (QoL) was examined in
patients with grass pollen-induced rhinoconjunctivitis. Patients (n = 855) were
randomised to once-daily grass allergen tablets (2,500; 25,000; or 75,000 SQ-T
Phleum pratense extract; GRAZAX or placebo. Treatment was initiated 8 weeks
before the start of the grass pollen season and continued throughout. If symptoms
were present, patients received loratadine or placebo rescue medication. There
were three major findings: in patients using loratadine, grass allergen tablets
provided QOL benefits over placebo; Rhinoconjunctivitis Quality of Life
Questionnaire (RQLQ) score was 17% (p = 0.006) and 20% (p = 0.020) greater with
75,000 SQ-T tablet than with placebo at first and second seasonal visit,
respectively; in patients not using loratadine, grass allergen tablets improved
QoL more than placebo; RQLQ score was 21% greater (p = 0.021) with 75,000 SQ-T
tablet at second seasonal visit; grass tablets (without loratadine) had a greater
effect on QoL than loratadine alone. RQLQ score was 26% (p = 0.014) greater with
75,000 SQ-T tablets than loratadine at second seasonal visit. These data show
that sublingual immunotherapy with grass allergen tablets improves QOL in
allergic rhinoconjunctivitis, reduces symptoms, and that this effect is greater
than rescue antihistamine alone.
PMID- 17033901
TI - Minimally important change determined by a visual method integrating an anchor
based and a distribution-based approach.
AB - BACKGROUND: Minimally important changes (MIC) in scores help interpret results
from health status instruments. Various distribution-based and anchor-based
approaches have been proposed to assess MIC. OBJECTIVES: To describe and apply a
visual method, called the anchor-based MIC distribution method, which integrates
both approaches. METHOD: Using an anchor, patients are categorized as persons
with an important improvement, an important deterioration, or without important
change. For these three groups the distribution of the change scores on the
health status instrument are depicted in a graph. We present two cut-off points
for an MIC: the ROC cut-off point and the 95% limit cut-off point. RESULTS: We
illustrate our anchor-based MIC distribution method determining the MIC for the
Pain Intensity Numerical Rating Scale in patients with low back pain, using two
conceivable definitions of minimal important change on the anchor. The graph
shows the distribution of the scores of the health status instrument for the
relevant categories on the anchor, and also the consequences of choosing the ROC
cut-off point or the 95% limit cut-off point. DISCUSSION: The anchor-based MIC
distribution method provides a general framework, applicable to all kind of
anchors. This method forces researchers to choose and justify their choice of an
appropriate anchor and to define minimal importance on that anchor. The MIC is
not an invariable characteristic of a measurement instrument, but may depend,
among other things, on the perspective from which minimal importance is
considered and the baseline values on the measurement instrument under study. A
balance needs to be struck between the practicality of a single MIC value and the
validity of a range of MIC values.
PMID- 17033902
TI - Testing relationships between clinical and non-clinical variables in xerostomia:
a structural equation model of oral health-related quality of life.
AB - OBJECTIVES: The aim of the study was to systematically test Wilson and Cleary's
[Wilson IB, Cleary PD. JAMA 1995; 273: 59-65] conceptual model of the direct and
mediated pathways between clinical and non-clinical variables in relation to the
oral health-related quality of life (OHRQoL) of patients with xerostomia.
METHODS: We collected measures of clinical variables, self-reported symptoms,
OHRQoL, global oral health perceptions and subjective well-being from 85 patients
attending outpatient clinics. RESULTS: Structural equation modelling indicated
support for the dominant direct pathways between the main levels of the model;
more severe clinical signs predicted worse patient reported symptoms; worse
symptom perception was associated with a lower functional status as measured by
OHRQoL; and lower OHRQoL predicted worse global oral health perceptions. There
was no relationship between the final two levels of the model; global oral health
perceptions and subjective well-being. Subjective well-being was associated
instead with earlier non-adjacent levels; biological variables, symptoms and
functional status. These pathways were both direct (salivary flow-well-being,
functioning-well-being) and indirect (clinical signs-well being, symptom status
well-being). There were also indirect pathways; most notably, the impact of
clinical variables on OHRQoL was mediated by patient reported symptom status.
CONCLUSIONS: The results support Wilson and Cleary's conceptual model of patient
outcomes as applied to a chronic oral health condition and highlight the
complexity of (inter)relationships between key clinical and non-clinical
variables. Further conceptual development of the model is discussed, particularly
the role of individual difference factors, and theoretical and methodological
issues in OHRQoL research are highlighted.
PMID- 17033903
TI - Quality of life, health status and clinical outcomes in Type 2 diabetes patients.
AB - This study examines relationships between patient reported outcomes (PROs) and
clinical outcomes in Type 2 diabetes mellitus (T2DM). Patients at the outpatient
clinics of a university hospital completed measures of generic health status (SF
12), diabetes-specific quality of life (Audit of Diabetes Dependent Quality of
Life - ADDQoL), and depressive symptoms (Center for Epidemiologic Studies
Depression - CES-D). Patient reported data were merged with a retrospective
collection of clinical and utilization data, including HbA1C, from electronic
medical records. A Charlson comorbidity score, diabetes complications score, BMI,
and total number of ER and hospital visits were calculated. Usable response rate
was 44.3% (n = 385). Patients were dichotomized into glycemic control levels
based on the ADA recommended A1C level < 7.0, vs. >or= 7.0. The ADDQoL, PCS-12,
and MCS-12 scores were separately examined as dependent variables using
hierarchical regression models, with glycemic control as the primary explanatory
variable, and controlling for demographics and clinical variables including
comorbidities and complications. Glycemic control was not a significant predictor
in any regression model. Obesity was a significant predictor leading to poorer
PCS-12 and MCS-12 scores, while depressive symptoms significantly resulted in
lower PCS-12, MCS-12 and ADDQoL scores. These and other factors related to self
management behaviors may contribute to a greater understanding of how to
intervene with patients with T2DM. The use of such PROs alongside biomedical
measures such as A1C is recommended.
PMID- 17033904
TI - Quality of life of mental health consumers in Hong Kong: Analysis of service
perceptions.
AB - OBJECTIVES: Successful psychiatric rehabilitation entails fostering overall
quality of life of individuals recovering from severe mental illnesses.
Understanding how service-related perceptions may be related to quality of life
can be useful in improving the effectiveness of community-based care. This study
investigated the quality of life of mental health consumers using a service
oriented paradigm. METHODS: 162 mental health consumers from community-based
psychiatric rehabilitation centers were interviewed. Analyses were conducted to
investigate the relationships between service perceptions (perceived treatment
coercion, rehabilitation needs, and continuity of care) and quality of life.
RESULTS: Physical health quality was negatively related to rehabilitation needs.
Mental health quality was negatively related to both rehabilitation needs and
poorer continuity of service. Life satisfaction was negatively related to poorer
continuity of service and higher perceived treatment coercion. CONCLUSIONS: This
study highlighted the significance of service perceptions in the well-being of
individuals with severe mental illness.
PMID- 17033905
TI - Validation of the asthma impact survey, a brief asthma-specific quality of life
tool.
AB - BACKGROUND: The Asthma Impact Survey (AIS-6) is a new six question asthma outcome
tool for which information on validity has not been published. OBJECTIVE: To
provide validation for the AIS-6 as a brief asthma-specific quality of life tool.
METHODS: Surveys were sent to a random sample of members of a large managed care
organization who were at least 35 years of age and in the two-year period
preceding the survey had either (1) at least one documented asthma-related
medical encounter, or (2) at least a 6 months supply of asthma medication
dispensed. In addition to the AIS-6, the survey included a validated quality of
life tool [the mini-Asthma Quality of Life Questionnaire (AQLQ)]; a validated
asthma control questionnaire [the Asthma Therapy Assessment Questionnaire
(ATAQ)]; a validated symptom severity scale (AOMS); and information regarding
demographics, co-morbidities, asthma severity, and asthma management. The results
of the AIS-6 were compared to the results of the other tools by means of
correlation and factor analysis. Independent predictors of AIS-6 and AQLQ scores
were determined by multiple stepwise linear regression analyses. RESULTS: AIS-6
scores were significantly related to female sex, educational level, income,
smoking, body mass index (BMI), COPD, steroid use, and hospitalization history in
bivariate analyses. The AIS-6 score significantly correlated (r = - 0.84, p <
0.0001) with the AQLQ total score and loaded on the three factors (activity,
symptoms, and concern/bother) reflected by the survey information and on which
the AQLQ also loaded. Significant but somewhat smaller correlations were found
between the AIS-6 and the ATAQ (r = 0.70, p < 0.0001) and the AOMS (r = 0.55, p <
0.0001). Independent predictors were the same for the AIS-6 and AQLQ and included
oral steroid use, COPD history, BMI, female sex, educational level, and
hospitalization in the past year. CONCLUSION: These data support the validity of
the short six-question AIS-6 as an asthma-specific quality of life tool.
PMID- 17033906
TI - Health status and quality of life after acute exacerbations of chronic
obstructive pulmonary disease.
PMID- 17033907
TI - The development of a new measure of quality of life in the management of gastro
oesophageal reflux disease: the Reflux questionnaire.
AB - INTRODUCTION: This paper reports on the development of a new measure of health
related quality of life for use among patients with gastro-oesophageal reflux
disease (GORD), funded as part of the REFLUX trial. This is a large UK multi
centre trial that aims to compare the clinical and cost effectiveness of minimal
access surgery with best medical treatment for patients with GORD within the NHS.
METHOD: Potential items were identified via a series of interviews and focus
groups carried out with patients who were receiving/had received medical or
surgical treatment for GORD. The final measure consisted of 31 items covering 7
categories (Heartburn; Acid reflux; Wind; Eating and swallowing; Bowel movements;
Sleep; Work, physical and social activities). The measure produced two outputs: a
quality of life score (RQLS) and five Reflux symptom scores. Reliability
(internal consistency), criterion validity with the SF-36 and, sensitivity to
change in terms of relationship with reported change in prescribed medication
were assessed amongst a sample of 794 patients recruited into the trial. RESULTS:
The measure was shown to be internally consistent, to show criterion validity
with the SF-36 and sensitive to changes in patients use of prescribed medication
at baseline and 3 month follow-up. DISCUSSION: The Reflux questionnaire is a new
self-administered questionnaire for use amongst patients with GORD. Initial
findings suggest that the new measure is valid, reliable, acceptable to
respondents and simple to administer in both a clinical and research context.
PMID- 17033908
TI - Responsiveness of the EuroQol (EQ-5D) and the Nottingham Health Profile (NHP) in
elderly patients with femoral neck fractures.
AB - INTRODUCTION: The objective of this study was to evaluate the internal and
external responsiveness of the EuroQol (EQ-5D) and the Nottingham Health Profile
(NHP) and to evaluate the overlap of change scores from the two instruments.
METHODS: Sixty patients with femoral neck fractures treated with internal
fixation at a university hospital participated. Internal responsiveness was
assessed using a paired t-test and the standardised response mean (SRM) for
patients with displaced fractures hypothesised to deteriorate between baseline
and the 6-month follow-up. In the analyses of external responsiveness, receiver
operator characteristics (ROC) and logistic regression were employed to assess
the correspondence between the chosen external criterion (EC) defining fracture
displacement, i.e. displaced vs. undisplaced fractures, and the change scores
from the EQ-5D and the NHP. The overlap in change scores for the overall scores
and comparable subdimensions of the two instruments was evaluated by
correlational analyses. RESULTS: The SRM were large and the change in HRQoL over
time was statistically significant for both instruments in patients with
displaced fractures. A correspondence was found between the EC and change scores
for both questionnaires. The correlation coefficients between the change scores
for the overall scores and comparable subdimensions of the two instruments ranged
from relatively small to moderate. CONCLUSIONS: The results yielded support for
the internal and external responsiveness of the EQ-5D and the NHP and indicated
an advantage for the EQ-5D. The empirical overlap between change scores from the
two instruments was limited.
PMID- 17033909
TI - Randomized trial results of quality of life comparing whole abdominal irradiation
and combination chemotherapy in advanced endometrial carcinoma: A gynecologic
oncology group study.
AB - OBJECTIVE: To prospectively compare quality of life (QOL) outcomes in patients
with advanced endometrial cancer treated with whole abdominal irradiation (WAI)
or doxorubicin-cisplatin (AP) chemotherapy. METHODS: Using the Fatigue Scale
(FS), Assessment of Peripheral Neuropathy (APN), Functional Alterations due to
Changes in Elimination (FACE), and Functional Assessment of Cancer Therapy
General (FACT-G), QOL was measured at: pre-treatment, end of treatment (EOT), and
3 and 6 months post-treatment. RESULTS: 317 of 396 eligible patients provided a
baseline QOL assessment. The AP arm produced a statistically significant survival
benefit along with greater toxicities, including peripheral neuropathy persisting
up to 6 months. WAI patients reported worse FS (p < 0.001) and FACE (p < 0.001)
scores at EOT and poorer FACE scores 3 months post-treatment (p = 0.004) compared
to AP patients. APN scores were significantly worse among AP patients at EOT, and
3 and 6 months post-treatment (p < 0.001 for all). There is no indication that
FACT-G scores differed between the two arms at any assessment point. CONCLUSIONS:
The trade-off for increased survival with AP is its potential for clinically
significant peripheral neuropathy. This should be discussed with patients,
particularly those who work with their hands or on their feet, in weighing
therapeutic choices. Further research is needed to manage side effects having an
enduring impact on QOL.
PMID- 17033910
TI - Quality of life in HIV subtype C infection among asymptomatic subjects and its
association with CD4 counts and viral loads--a study from South India.
AB - OBJECTIVE: To study the association between quality of life (QOL) domains and
biological markers of disease progression of HIV infection, i.e. viral load (VL)
and CD4 counts among asymptomatic subjects with HIV subtype C infection in South
India. DESIGN: Quality of life was measured using the locally validated version
of the WHOQOL HIV-BREF. The subjects were neurologically asymptomatic, non
psychiatrically ill HIV infected men and women participating in a cohort study.
RESULTS: The results indicated mixed findings, with some QOL dimensions being
associated with high VLs and low CD4 counts while several others did not show any
associations. Significant associations were seen between low CD4 counts and the
psychological and social relationships domain, with lower mean scores in these
domains being reported by subjects having CD4 counts <200/mm. However, there were
no significant differences between the CD4 subgroups for the domains related to
physical health, level of independence, environment, and spirituality domains.
Significant lower mean QOL scores were found in the highest VL subgroup compared
to other groups for the following WHOQOL HIV-BREF domains: physical,
psychological, level of independence, and environmental. CONCLUSIONS: In this
sample of HAART naive asymptomatic HIV infected subjects, some QOL dimensions
were associated with the biological markers of disease progression i.e. VL and
CD4 counts, while several were not. The associations were significant only in the
high VL and low CD4 groups.
PMID- 17033911
TI - Girls growing through adolescence have a higher risk of poor health.
AB - INTRODUCTION: Self rated health, in adult population, is strongly associated with
mortality and life expectancy. In younger people this association is less
evident, but it may anticipate a similar risk in adult life. Our research, based
on the HBSC (Health Behaviour in School-Aged Children) International
collaboration, contributes to deepen the knowledge in this field by monitoring
adolescents' health through a multi-national survey involving 29 European
countries, plus North America (Canada and USA) and Israel. METHODS: Following an
established methodology, the HBSC survey has elaborated a questionnaire on health
and health behaviour, filled in by a representative national sample of 11-, 13-
and 15-year-old boys and girls. The sample is constituted of more than 160,000
subjects interviewed during the 2001/2002 survey. Reported symptoms and self
rated health have been analysed by sex and age and through the different
countries. RESULTS: Girls resulted to have a poorer perception of their health,
with respect to males, at all ages and in all countries (Overall OR = 1.70, 95%
CI: 1.66-1.76). Age increases this risk both for males and females, with an
average increase of 32% (95% CI: 29-34%) per year in the age-range 11-15. The
situation is similar for reported symptoms, with an overall OR of 1.81 (95% CI:
1.77-1.85) for females of reporting three or more symptoms at least once a week;
also this risk increases of 26% (95% CI: 24-27%) per year during the pre
adolescence phase. In both cases it could be shown a significant interaction
effect between age and gender: OR = 1.19 (CI: 1.15-1.23) for perceived health and
OR = 1.26 (CI: 1.23-1.29) for reported symptoms in females with respect to males.
CONCLUSIONS: Even if adolescence is described as the healthiest period of life, a
consistent minority of young people perceive and report a poor health and a high
number of symptoms. Females are constantly in a worse position than males and
older age groups are worse than younger ones.
PMID- 17033912
TI - Health-related quality of life and mental health problems after a disaster: are
chronically ill survivors more vulnerable to health problems?
AB - Studies have shown that the chronically ill are at higher risk for reduced health
related quality of life (HRQL) and for mental health problems. A combination with
traumatic events might increase this risk. This longitudinal study among 1216
survivors of a disaster examines whether chronically ill survivors had a
different course of HRQL and mental health problems compared to survivors without
chronic diseases. HRQL and mental health problems were measured 3 weeks, 18
months and 4 years post-disaster. Data on pre-disaster chronic diseases was
obtained from the electronic medical records of general practitioners. Random
coefficient analyses showed significant interaction effects for social
functioning, bodily pain and emotional role limitations at T2 only. Chronically
ill survivors did not consistently have a different course of general health,
physical role limitations, and mental health problems. In conclusion, chronic
diseases were not an important risk factor for impaired HRQL and mental health
problems among survivors.
PMID- 17033913
TI - Quality of life and continence in patients with spina bifida.
AB - PURPOSE: Spina bifida (SB) is the most common congenital cause of incontinence in
childhood. This study attempts to determine the relationships between
urinary/faecal incontinence, methods of management, and Health Related Quality of
Life (HRQoL) in people with SB. PATIENTS AND METHOD: A total of 460 patients (300
adults and 160 adolescents) from six centres in France have taken part in this
cross-sectional study. Clinical outcome measures included walking ability,
urinary/faecal continence, and medical management. HRQoL was assessed using the
SF36 in adults and the VSP in adolescents and their parents. Univariate and
multivariate analysis was used to determine the relationships between clinical
parameters and HRQoL. RESULTS: HRQoL were significantly lower than in the general
population. Adult women had significantly lower scores than men, and adolescent
females had significantly lower scores for psychological well being. We did not
found strong relationship between incontinence and HRQoL in this population.
Moreover patients surgically managed for urinary/fecal incontinence did not show
significantly higher scores of HRQoL. CONCLUSION: Using generic HRQoL measures,
urinary/faecal incontinence and their medical management may not play a
determinant role in HRQoL of persons with SB. However many other factors affect
HRQoL in these patients. A longitudinal study design is recommended to assess
whether incontinence management is associated with improved HRQoL.
PMID- 17033914
TI - [Abstracts of the 50th Austrian Ear Nose and Throat Congress, September 2006,
Klagenfurt].
PMID- 17033915
TI - Psychopathological characteristics and treatment response of first episode
compared with multiple episode schizophrenic disorders.
AB - OBJECTIVE: The aim was to investigate the hypothesis that patients with first
episode schizophrenic disorders have a more favorable treatment response than
those with multiple episodes. METHOD: A total of 400 inpatients from an ongoing
multi-centre, follow-up program who fulfilled ICD-10 criteria for schizophrenic
disorders (F2) were assessed at admission to and discharge from hospital using
the Positive and Negative Syndrome Scale (PANSS). RESULTS: At admission, first
episode patients (n = 121) showed higher levels of positive symptoms (PANSS
positive subscore) and lower ones of negative symptoms (PANSS negative subscore)
than multiple episode patients (n = 279), whereas the global disease severity
(PANSS total score) was comparable. Analyses of covariance revealed that
treatment response (adjusted symptom levels at discharge) was more favorable in
first-episode patients, with respect to both positive and negative symptoms.
CONCLUSION: The results are compatible with the hypothesis that treatment
response becomes less favorable during the course of schizophrenic illness. This
finding might be associated with progressive neurobiological alterations.
PMID- 17033916
TI - Case report: Cerebral air embolization in the electrophysiology laboratory during
transseptal catheterization: curative treatment of acute left hemiparesis with
prompt hyperbaric oxygen therapy.
AB - We present a case of a 44 year-old man with medically refractory symptomatic
paroxysmal atrial fibrillation in whom the initial attempt at left atrial
catheter ablation was complicated by coronary and cerebral arterial air
embolization during transseptal catheter exchange. The manifestations,
management, and long term outcomes are detailed. Following the case report is a
review of published reports and contemporary management strategies for treatment
of acute air embolization. Dramatic clinical consequences can be aborted by
prompt intervention including volume loading, oxygenation, lidocaine, and
hyperbaric oxygen therapy.
PMID- 17033917
TI - Success rate of catheter ablation in atrial flutter: comparison of a 4- or 5-mm
tip electrode catheter with an 8-mm tip electrode catheter.
AB - BACKGROUND: Radio frequency (RF) energy is capable of interrupting the reentrant
circuit of atrial flutter and curing the arrhythmia. The development of 8-mm tip
catheter provides more tissue damage and has offered the promise of improved
success. The purpose of our study was to determine if the acute and long-term
success with the 8-mm tips were superior to the 4- or 5-mm tips. MATERIALS AND
METHODS: The outcomes of the first 20 patients in whom an 8-mm tip catheter was
used were compared with the previous 20 patients in whom a 4-or 5-mm tip catheter
was used. Procedural (acute) ablation success was defined by creation of bi
directional isthmus block. Long-term success was defined as the prevention of
clinically evident atrial flutter (AFl) as determined by the absence of symptoms
or maintenance of sinus rhythm on electrocardiogram, six months to one year after
the procedure. RESULTS: Compared to the 4- or 5-mm tip, the 8-mm catheter tip was
associated with a reduced ablation duration {22.3 +/- 16 versus 11.5 +/- 5 min (p
= 0.0078)}, a lower mean number of ablations {13.5 +/- 9.9 versus 6.8 +/- 2.9 (p
= 0.0065)} and a reduced procedure time {1.8 +/- 0.7 versus 1.1 +/- 0.5 h (p =
0.0032)}. Acute success was 95% in the 4- or 5-mm group versus 80% in the 8-mm
group (p = NS), but long-term success was higher in the 8-mm group than the 4- or
5-mm group (87.5 versus 63.2%, p = 0.0436). CONCLUSIONS: Eight-millimeter tip
catheters for AFl shorten procedure time, reduce the duration and number of
ablations and accomplish bi-directional block when compared with smaller tipped
catheters. The long-term success rate is better with the 8-mm tips and should be
the preferred catheter for RF ablation of AFl.
PMID- 17033918
TI - Breast cancer incidence trends in deprived and affluent Scottish women.
AB - OBJECTIVE: Breast cancer is commoner in the affluent and breast cancer rates in
many countries are rising; it remains unclear whether this incidence rise is
consistent across the different socio-economic groups. The rising incidence of
breast cancer may be related to changes in population risk factor profiles. This
study aimed to determine breast cancer incidence trends in women of different
socio-economic categories and whether these trends were related to breast cancer
risk factor trends. DESIGN: Data on breast cancer incidence rates by deprivation
quintile in Scotland 1991-2000 were analysed using linear regression. Data on
first births at late maternal age, BMI trends (based on the Scottish Health
Surveys) and breast screening uptake trends in the different categories were also
analysed and their relation to breast cancer incidence trends explored.
POPULATION AND SETTING: Breast cancer incidence data was based on all women in
Scotland. BMI data was based on representative cross-sectional survey data from
the Scottish Health Surveys-women in the 1995, 1998 and 2003 surveys were 16-64,
16-74 and aged 16 and over, respectively. First birth data was based on all women
aged 35-39 in Scotland. Breast screening uptake data was studied in women of
screening age, that is, aged 50-64. RESULTS: Breast cancer incidence rates in
Scottish women are rising in parallel across all socio-economic categories and
the incidence gap between deprived and affluent still remains. Since the late
1980s, numbers of first birth in Scottish women aged 35-39 have risen
dramatically, especially in the affluent, but numbers were stable before this.
The prevalence of obesity and mean BMI has increased over time in all socio
economic classes but BMI continues to be higher in the deprived. Uptake of
screening invitations has increased in all socio-economic groups. CONCLUSIONS:
Breast cancer is rising in women of all socio-economic status in Scotland and the
deprived-affluent gap remains. Trends in late age at first pregnancy, prevalence
of obesity and screening uptake do not fully explain the observed trends.
PMID- 17033919
TI - Male breast cancer: a review of clinical management.
AB - AIMS: Male breast cancer incidence is 1% of all breast cancers and is increasing.
We aim to present an overview of male breast cancer with particular emphasis on
clinical management. METHODS: Studies were identified by an online search of
literature in the MEDLINE database till June 2006 followed by an extensive review
of bibliographies. RESULTS: Increased risk factors include genetic predisposition
as in BRCA2 families; testicular dysfunction due to chromosomal abnormality such
as Klinefelter's syndrome or environmental factors such as chronic heat exposure
and radiation. Clinical assessment with biopsy is the hallmark of diagnosis.
Earlier presentations are becoming commoner but there are wide geographical
differences. Surgical treatment involves simple or modified radical mastectomy
along with surgical assessment of the axilla, either via sentinel node biopsy in
clinically node-negative disease or axillary sampling/clearance in node-positive
disease. Reconstructions for restoring body image have been recently reported.
Indications for adjuvant therapies are similar to that in women. For metastatic
disease, tamoxifen is still the mainstay for oestrogen receptor positive disease.
For oestrogen receptor negative disease, doxorubicin based chemotherapy regimens
are used. In addition, the oft neglected psychological aspects of men having a
"cancer of women" are increasingly being recognised. CONCLUSIONS: There is, thus,
need for further increasing awareness among men to reduce stigma associated with
presentation of symptoms related to breast. This should be in addition to
stressing to clinicians the ways of earlier detection and tailor-made "gender
oriented" treatment of breast cancer in men.
PMID- 17033920
TI - Accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes as a
triage test in breast cancer staging.
AB - INTRODUCTION: Axillary node fine needle aspiration cytology (FNAC) has the
potential to triage women with operable breast cancer to initial nodal surgical
procedure. Because of variability in the reported accuracy of this test its role
and clinical utility in pre-operative staging remains controversial. METHODS: We
retrospectively evaluated the accuracy of ultrasound-guided axillary FNAC in all
consecutive clinically T1-2 N0-1 breast cancers that had undergone this test (491
biopsies). We included subjects with clinically or sonographically indeterminate
or suspicious nodes. Pathological node status was used as the reference standard
(based on axillary dissection or sentinel node biopsy). RESULTS: Sensitivity of
node FNAC was 72.6% (67.3-77.9) and specificity was 95.7% (92.5-98.8) for all
cases, sensitivity was lower at 64.6% (59.3-70.0) if inadequate cytology was
included as a negative result. FNAC sensitivity was highest in women with
clinically suspicious nodes [92.5% (88.2-96.7)] and lowest in women with
sonographically abnormal and clinically negative nodes [50.0% (41.3-58.7)].
Specificity was high in both groups, 81.2% (54.5-96.0) and 97.2% (94.6-99.9),
respectively. The false-negative rate was 15.3% (12.1-18.5), the false-positive
rate was 1.4% (0.4-2.5), and the inadequacy rate was 10.8% (8.0-13.5). The
likelihood of node FNAC being positive was significantly associated with tumour
grade and stage, and the number of nodes involved with metastases. DISCUSSION:
Our data show that axillary FNAC has moderate sensitivity (which varies according
to selection criteria for the test) and consistently high specificity, is
associated with low inadequacy and very few false positives. We estimate that its
use would have improved triage to initial nodal procedure in about one quarter of
our cases. If one accepts the premise that initial surgical staging of the axilla
should be based on all information available through pre-operative diagnosis,
then axillary FNAC should be adopted routinely into clinical practice.
PMID- 17033921
TI - The effects of radiotherapy for the treatment of contralateral breast cancer.
AB - Radiotherapy following breast-conserving surgery for the treatment of first
primary breast cancer is the standard of care and is widely used despite its
small survival benefit. The effects of radiotherapy in metachronous contralateral
breast cancer are unknown. We examined the use of radiotherapy and its effect on
cause-specific and all-cause mortality among women with metachronous
contralateral breast cancer treated with breast-conserving surgery in community
settings. Using data from the 1985-2000 Surveillance, Epidemiology, and End
Results program, we identified women with stage 0-III metachronous contralateral
breast cancer that occurred at least six months after stage 0-III first primary
breast cancer. Cause-specific and all-cause mortality of women age 40-69 who did
and who did not receive radiotherapy following breast-conserving surgery for
metachronous contralateral breast cancer were compared in proportional hazard
models using propensity scores to balance covariates by radiotherapy use. We
adjusted for misclassification of radiotherapy use. Based on misclassification
corrected analyses, 43.2 percent of 1,083 women with metachronous contralateral
breast cancer did not receive radiotherapy after BCS. After adjustment for
propensity scores and radiotherapy misclassification, women who did not receive
radiotherapy had 2.2 times greater risk of cause-specific and 1.7 times greater
risk of all-cause mortality. In community settings, a high percentage of women
with stage 0-III metachronous contralateral breast cancer did not receive
radiotherapy following breast-conserving surgery. Unlike the small survival
benefit of radiotherapy after first primary breast cancer, omission of
radiotherapy after metachronous contralateral breast cancer significantly
increased the risk of cause-specific and all-cause mortality.
PMID- 17033922
TI - Characterization of molecular and structural determinants of selective estrogen
receptor downregulators.
AB - Antiestrogens used for breast cancer therapy can be categorized into two classes
that differ in their effect on estrogen receptor (ER) alpha stability. The
selective estrogen receptor modulators (SERMs) stabilize ER alpha and the
selective estrogen receptor downregulators (SERDs) cause a decrease in cellular
ER alpha levels. A clinically relevant antiestrogen, GW7604, appears to work
through a SERD-like mechanism, despite sharing the same molecular scaffold as 4
hydroxytamoxifen, a SERM. In order to investigate potential structural features
of GW7604 responsible for SERD activity, GW7604 and two analogs were synthesized
using a new, improved synthetic route and tested for their effects on ER alpha
function and cell proliferation. The two analogs, which have an acrylamide or a
methyl vinyl ketone replacing the acrylic acid group of GW7604, display lower
binding affinity for ER alpha than GW7604, but show similar antagonism of
estradiol-induced activation of ER alpha-mediated transcription as GW7604 and
inhibit estradiol-induced proliferation of the MCF-7 cell line with a similar
potency as GW7604. Unlike GW7604, neither analog has a significant effect on
cellular ER alpha levels, suggesting that the carboxylate is a key determinant in
GW7604 action and, for the first time, showing that this group is responsible for
inducing ER alpha degradation in breast cancer cells.
PMID- 17033923
TI - Magnetic resonance imaging of breast lesions--a pathologic correlation.
AB - Magnetic resonance imaging of the breast is useful in assessing breast lesions.
An understanding of the pathologic characteristics of the tumors may help to
understand these magnetic resonance imaging observations.Large lesional size (>10
mm), ill-defined margin, and irregular outlines are associated with malignancy.
These correlate with the pathological features of breast tumor, characterized by
rapid growth rate, large size, and infiltrative growth pattern, invasion into
stroma resulting in desmoplasia, and hence irregular outline and margin. The
detection and estimation of tumor extent of invasive lobular carcinoma is
problematic, even with magnetic resonance imaging, which is considered the most
sensitivity. This inaccuracy likely derives from the characteristic linear,
single cells infiltration growth pattern of the tumor, which is also often
underestimated by clinical examination. Estimation of tumor extent after
neoadjuvant chemotherapy is also essential but problematic by imaging, as the
shrunken tumor becomes fibrotic, with stromal hyalinization, diminished
microvasculature and tumor break up causing size underestimation. Non-enhancement
of breast tumors occurs in about 8% of cases correlates with diffuse growth
pattern, particularly of infiltrative lobular carcinoma. The observation of
disproportionately high non-enhancing ductal carcinoma in situ remains an enigma.
Finally, early rim enhancement correlates with small cancer nests, low ratio of
peripheral to central fibrosis and high ratio of peripheral to central
microvessel density. These may be related to increased vascular endothelial
growth factor mediated increased microvessel density as well as increased
permeability, which manifest as increased rapid contrast uptake and dissipation.
PMID- 17033924
TI - Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few
associations with breast cancer susceptibility and progression.
AB - The importance of matrix metalloproteinases and their inhibitors in tumor
progression is well documented. We wanted to investigate if single nucleotide
polymorphisms (SNPs) in the promoter regions of these genes are associated with
susceptibility to or progression of breast cancer. In this, so far largest case
control study, we genotyped eight SNPs in the MMP1, MMP2, MMP3, MMP9, MMP13, RECK
and TIMP3 genes in a well-characterized breast cancer series of 959 cases and 952
controls from Sweden. Even though we did not correct for multiple comparisons,
only a few associations were noted. We observed a moderately increased risk for
the TT homozygotes of the MMP9-1562 C/T SNP (OR 1.88, 95% CI 0.97-3.63) and for
the C allele carriers of the TIMP3-1296 T/C SNP (OR 1.25, 95% CI 1.05-1.50). In
the survival analysis, only the TC heterozygotes of the RECK-420 T/C SNP showed a
better survival compared to the TT homozygotes (P = 0.02 in all cases and P =
0.03 in lymph node negative cases). None of the other SNPs conferred an increased
breast cancer risk, nor did they correlate with survival. A combination of the
585 TT homozygosity in the RECK gene and the -1296 TT homozygosity in the TIMP3
gene correlated with estrogen and progesterone receptor status (OR 1.81, 95% CI
1.03-3.21 and OR 2.10, 95% CI 1.18-3.86, respectively), and a combination of the
1306 TT homozygosity in the MMP2 gene and the -1562 CC homozygosity in the MMP9
gene with progesterone receptor status (OR 2.34, 95% CI 1.08-5.08). Although our
study suggests some correlations between the studied SNPs and the progression of
breast cancer, the rarity of the risk genotypes limits their usefulness in the
clinic.
PMID- 17033925
TI - Reproductive factors and breast cancer risk among older women.
AB - Reproductive factors have been shown to affect pre- and postmenopausal breast
cancer risk differently, but whether there are additional age-specific
differences among menopausal women as they age has not been clarified. We
analyzed data from a large population-based case-control study that included
1,508 breast cancer cases and 1,556 controls, aged 20-98 years, who completed an
in-home interviewer-administered questionnaire. The following subgroups were
created to examine if the associations between reproductive factors and breast
cancer risk varied by age- and menopausal-status: premenopausal (n=968),
postmenopausal <65 years (n=1,045), postmenopausal >or=65 years (n=958). Among
postmenopausal women >or=65 years, ever having breastfed decreased risk (odds
ratio (OR)=0.67, 95% confidence interval (CI)=0.48, 0.92), and a strong dose
response relationship was observed for longer durations of breastfeeding (P
trend=0.02), with the most pronounced protective effect observed for >or=14
months of breastfeeding (OR=0.40, 95% CI=0.21,0.76). Late age at first birth
(AFB) and older age at last birth (ALB) were associated with non-statistically
significant increases in breast cancer risk in this older group, while late age
at menarche and surgical menopause decreased risk. ORs for multiparity were close
to the null. Among premenopausal women and postmenopausal women <65 years,
multiparity significantly decreased risk, and older AFB nonsignificantly
increased risk. Our findings suggest that the well-known protective effect of
multiparity attenuates with older age. Moreover, breastfeeding, one of the few
potentially modifiable risk factors for breast cancer, was an important factor in
decreasing risk among older parous postmenopausal women.
PMID- 17033926
TI - Thirty-year follow-up of chemo/hormonal therapy in node-positive breast cancer.
AB - Results of a thirty-year follow-up of a clinical trial of chemo-hormonal therapy
are reported. Eligible patients had recently diagnosed operable breast cancer,
positive lymph nodes, no previous history of cancer, age less than 76 years, and
no evidence of metastatic disease. A total of 311 patients were stratified by
estrogen receptor (ER) status and number of axillary nodes involved with tumor.
After stratification, patients were randomly assigned to one of three treatment
regimens: cyclophosphamide, methotrexate and 5-fluorouracil (CMF) for 1 year; CMF
chemotherapy combined with anti-estrogen therapy (tamoxifen) for 1 year; or CMF
plus tamoxifen with BCG during the second year. The endpoint of the trial was a
first recurrence. Factors measured at diagnosis and used in the analyses were
age, body mass index, ER status, menopausal status, number of positive nodes,
tumor diameter, Charlson comorbidity index, socioeconomic status, and race.
Causes of death and incidence of other cancer primaries were obtained from death
certificates and medical records. Patients treated with tamoxifen had a
marginally longer disease-free survival (hazard ratio (HR)=0.83, 95% CI identical
with [0.66, 1.04]) and statistically significant longer overall survival
(HR=0.77, 95% CI identical with [0.63, 0.96]) that decreased with time. Incidence
of other primary cancers and causes of death were similar for the two treatment
groups. The addition of 1 year of tamoxifen to CMF therapy provides an early
disease-free and overall survival advantage; however long-term effects are
negligible. Similarly, the survival advantage of patients diagnosed with ER+
tumors persists for the first two decades after diagnosis.
PMID- 17033927
TI - Cost-effectiveness of exemestane versus tamoxifen as adjuvant therapy for early
stage breast cancer after 2-3 years treatment with tamoxifen in Sweden.
AB - Aromatase inhibitors are rapidly becoming the cornerstone of endocrine treatment
for advanced disease and are now also used as adjuvant treatment in early-stage
disease. The objective of this study was to assess the cost-effectiveness of
adjuvant treatment with exemestane versus tamoxifen for early-stage breast cancer
after 2-3 years treatment with tamoxifen in Sweden. The results are based on
findings in the Intergroup Exemestane Study (IES). IES was a randomized
controlled trial in which postmenopausal women who had received 2-3 years of
tamoxifen therapy following primary treatment of early-stage breast cancer, were
randomized to either continue on tamoxifen therapy or be switched to exemestane
therapy. The results showed a disease-free survival hazard ratio of exemestane
relative to tamoxifen in IES of 0.69. A Markov state-transition model was
developed to simulate consequences after the end of the clinical trial, and to
integrate the trial data with external data on mortality, costs and quality of
life specific for Swedish women. The cost per QALY gained was about euro 20,000
in the base case analysis without inclusion of consequences of coronary heart
disease. Inclusion of these events increased the cost-effectiveness ratio to
about euro 31,000. This means that, based on our assumption, sequential
exemestane treatment in early breast cancer is a cost-effective option compared
with tamoxifen alone, although more long-term data on overall survival and
consequences of adverse events would be valuable to increase the validity of the
analysis further.
PMID- 17033928
TI - The impact of breast cancer awareness and socioeconomic status on willingness to
receive breast cancer prevention drugs.
AB - PURPOSE: To find associations between knowledge about risk factors for breast
cancer and the socioeconomic status of healthy women, as well as their attitude
toward taking chemopreventive drugs. PATIENTS AND METHODS: Between April and
September 1999, 7135 healthy women completed questionnaires providing information
about their willingness to take chemopreventive drugs. Items in the questionnaire
included the sources of the information they had, their estimates of the
population and personal lifetime risk, and risk factors for breast cancer.
RESULTS: A total of 6597 questionnaires were evaluable. The responders' median
age was 44. Fifty-five percent of the women were willing to consider receiving
chemopreventive drugs to lower their risk for breast cancer. Participants who
estimated the population risk as being very high were more disposed to receive
chemoprevention (65.3%), as were women who estimated their own breast cancer risk
as being high (74.1%). A family history of breast cancer only had a low impact on
willingness to receive chemoprevention. Women with a family history of breast
cancer were willing to take chemopreventive agents in 57.2% of cases. The
multivariate analysis showed that knowing about risk factors and having a lower
educational level were factors positively correlated with willingness to consider
chemoprevention. CONCLUSION: These findings emphasize the role of estimations of
the risk of breast cancer for patients considering whether to accept
chemoprevention treatment. To date, only a few modern models of risk estimation
have been evaluated in relation to chemoprevention. There is a need for better
integration of professional risk estimations into clinical practice.
PMID- 17033929
TI - Computed tomography in suspected local breast cancer recurrence.
AB - PURPOSE: The purpose of this prospective study was to test computed tomography
(CT) in the evaluation of local breast cancer recurrence. MATERIALS AND METHODS:
Our study population included 103 women referred for mamma CT examination for
reasons of suspicious findings in a conservatively treated breast. In these
patients, both clinical and conventional imaging studies (mammography,
ultrasonography) features of local recurrences were non specific or suspicious.
The patients underwent breast CT before and 90 s after intra-venous contrast
medium administration. Criterion for cancer recurrence was detection of a lesion
with an enhancement of 20 UH or more. The final diagnosis was based on operative
histopathological findings or follow-up for over two years. RESULTS: Local
recurrence was confirmed on histology in 52 patients. CT identified 47 breast
recurrent cancers. False-positive contrast enhancement was seen in five patients.
CT showed 90% sensitivity, 90% specificity and 90% accuracy. CONCLUSION: Although
mamma CT examination proved to have a high diagnostic efficacy in evaluating
breast cancer recurrence, routine computed tomography is unnecessary for most
patients.
PMID- 17033930
TI - Teaching the imitation and spontaneous use of descriptive gestures in young
children with autism using a naturalistic behavioral intervention.
AB - Children with autism exhibit deficits in the imitation and spontaneous use of
descriptive gestures. Reciprocal Imitation Training (RIT), a naturalistic
imitation intervention, has ben shown to increase object imitation skills in
young children with autism. A single-subject, multiple-baseline design across
five young children with autism was used to determine whether RIT could be
adapted to target the imitation of descriptive gestures. All participants
increased their imitation of gestures in the treatment setting and on a
structured imitation assessment. Gains generalized to a novel therapist, setting,
and materials and maintained at a 1-month follow-up. Three participants also
increased their spontaneous use of descriptive gestures. These results provide
support for the effectiveness of a naturalistic intervention for teaching gesture
imitation.
PMID- 17033931
TI - Microbiological characteristics of a sandy loam soil exposed to tebuconazole and
lambda-cyhalothrin under laboratory conditions.
AB - Changes in microbiological properties of a sandy loam soil in response to the
addition of different concentrations of fungicide tebuconazole and pyrethroid
insecticide lambda-cyhalothrin were assessed under laboratory conditions. To
ascertain these changes, the potentially active soil microbial biomass,
concentrations of ammonium and nitrate ions, numbers of total culturable
bacteria, fungi, nitrogen-fixing bacteria, nitrifying and denitrifying bacteria
were determined. Substrate-induced respiration (SIR) increased with time in both
control (ranged from 13.7 to 23.7 mg/O(2)/kg(-1)/dry soil/h(-1)) and pesticide
treated soil portions. For both pesticides, SIR values ranged from 12-13 to 23-25
mg/O(2)/kg(-1)/dry soil/h(-1) on days 1 and 28, respectively. Also,
concentrations of nitrate and ammonium ions, numbers of total culturable
bacteria, denitrifying bacteria, nitrogen-fixing bacteria (for the insecticide)
and fungi (for the insecticide) were either unaffected or even stimulated by the
pesticide treatments. The adverse impacts of the pesticides were observed for
nitrate concentrations (on days 1 or 7), numbers of nitrifying bacteria (on day
1), denitrifying bacteria (for the insecticide on days 1 and 14), nitrogen-fixing
bacteria (for tebuconazole on day 1) as well as numbers of fungi in tebuconazole
treated soil (on days 1 and 14).
PMID- 17033932
TI - Do access experiences affect parents' decisions to enroll their children in
Medicaid and SCHIP? Findings from focus groups with parents.
AB - OBJECTIVE: The Covering Kids and Families (CKF) program seeks to expand health
insurance coverage for children by supporting community-based outreach and
enrollment. For the evaluation of CKF, researchers conducted focus groups to
explore parents' experiences accessing health care for their children, and to
assess whether these experiences affected decisions to enroll their children in
Medicaid or the State Children's Health Insurance Program (SCHIP). METHODS: In
May and June 2003, 13 focus groups were conducted in 5 cities--Everett, MA;
Denver, CO; Los Angeles, CA; Mena, AR; and San Antonio, TX. In each community,
groups were conducted with parents of children insured under Medicaid or SCHIP
and parents of uninsured children. Three groups were conducted with Spanish
speaking parents in two communities--Denver and Los Angeles. RESULTS: Access to
primary care was considered good by most parents with children in Medicaid and
SCHIP. Among parents of uninsured children, there was more variation in
perceptions of access to care. For parents of both uninsured and insured
children, access to dentists and specialists was more problematic. Spanish
speaking families reported numerous barriers to care due to language differences
and perceived discrimination. All focus group participants said that they placed
great value on health insurance. CONCLUSION: Even when parents encountered
problems accessing care, very few indicated that this discouraged them from
enrolling their children into Medicaid or SCHIP, or from renewing their
children's public coverage.
PMID- 17033933
TI - Doing the difficult and dangerous: the community program practice scale.
AB - The CPPS uses staff respondents to portray practices and program climate of
nonresidential mental health programs. We report psychometric analyses of 1,533
respondents in 165 programs. Confirmatory factor and partial credit analyses
identified eight practice and five climate subscales, all of which show adequate
psychometric properties. Program types are distinguished better by practices (R
(2) values .37 to .52) than by climate (R (2) values .09 to .23), as expected.
Multiple discriminant analysis and K-means cluster analysis illustrate how well
the CPPS distinguishes program differences. The CPPS offers a promising,
economical approach to measuring program practices in clinical trials comparing
service programs.
PMID- 17033934
TI - Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with
impaired spatial learning and reduced control of exploratory behavior.
AB - Coffin-Lowry Syndrome (CLS) is an X-linked syndromic form of mental retardation
associated with skeletal abnormalities. It is caused by mutations of the Rsk2
gene, which encodes a growth factor regulated kinase. Gene deletion studies in
mice have shown an essential role for the Rsk2 gene in osteoblast differentiation
and function, establishing a causal link between Rsk2 deficiency and skeletal
abnormalities of CLS. Although analyses in mice have revealed prominent
expression of Rsk2 in brain structures that are essential for learning and
memory, evidence at the behavioral level for an involvement of Rsk2 in cognitive
function is still lacking. Here, we have examined Rsk2-deficient mice in two
extensive batteries of behavioral tests, which were conducted independently in
two laboratories in Zurich (Switzerland) and Orsay (France). Despite the known
reduction of bone mass, all parameters of motor function were normal, confirming
the suitability of Rsk2-deficient mice for behavioral testing. Rsk2-deficient
mice showed a mild impairment of spatial working memory, delayed acquisition of a
spatial reference memory task and long-term spatial memory deficits. In contrast,
associative and recognition memory, as well as the habituation of exploratory
activity were normal. Our studies also revealed mild signs of disinhibition in
exploratory activity, as well as a difficulty to adapt to new test environments,
which likely contributed to the learning impairments displayed by Rsk2-deficient
mice. The observed behavioral changes are in line with observations made in other
mouse models of human mental retardation and support a role of Rsk2 in cognitive
functions.
PMID- 17033935
TI - Testing descriptive hypotheses regarding sex differences in the development of
conduct problems and delinquency.
AB - Accurate descriptions of sex differences in the development of childhood conduct
problems and adolescent delinquency will inform theories of their causes in
fundamentally important ways. Using data on 4,572 offspring of a national sample
of women, we tested descriptive hypotheses regarding sex differences. As
predicted, the magnitude of sex differences varied with age, suggesting that
multiple processes differentially influence levels of these behaviors in females
and males across development. During childhood, boys scored lower on measures of
cognitive ability and exhibited lower sociability and compliance and greater
hyperactivity, oppositional behavior, and conduct problems. Most of these
variables were associated with childhood conduct problems and adolescent
delinquency equally in females and males, but maternal delinquency and early
childhood sociability were correlated more strongly with childhood conduct
problems in males and childhood compliance predicted adolescent delinquency more
strongly in females. Both sexes exhibited both childhood-onset and adolescent
onset trajectories of delinquency. Although more males followed a childhood-onset
trajectory, there were few sex differences in the early childhood risk correlates
of either delinquency trajectory.
PMID- 17033936
TI - Power doppler ultrasound assessment of the relationship between age and ovarian
perifollicular blood flow in women undergoing in vitro fertilization treatment.
AB - PURPOSE: To examine the relationship between age and ovarian perifollicular blood
flow (PFBF) in women undergoing IVF. METHODS: Serial transvaginal power Doppler
ultrasound (PDU) scans to assess ovarian PFBF were performed prospectively
throughout the follicular phase of ovarian stimulation in women undergoing IVF.
The ultrasound assessment days were categorized according to day of hCG trigger.
RESULTS: A total of 1050 ovarian follicles from 34 women undergoing one IVF
treatment cycle were used for data analysis. The median age of the women was 38.5
years, ranging from 28 years to 44 years. There was a significant negative
correlation between age and ovarian PFBF on the day of hCG trigger or trigger day
minus 1, but not beforehand during the follicular phase. CONCLUSIONS: There was a
significant negative correlation between age and ovarian PFBF in women undergoing
IVF which was only observed very late in the follicular phase of ovarian
stimulation.
PMID- 17033937
TI - Genotyping of congenital adrenal hyperplasia due to 21-hydroxylase deficiency
presenting as male infertility: case report and literature review.
AB - We describe here two infertile male patients who were referred to our hospital
with azoospermia at the ages of 33 and 30 years, respectively. Hormonal
examinations led to a diagnosis of congenital adrenal hyperplasia (CAH) due to 21
hydroxylase deficiency in both patients. Genotyping revealed that the patients
had a homozygous I172N and a heterozygous compound I172N/IVS2-13A/C>G mutation,
respectively. Glucocorticoid replacement therapy succeeded in improving the
seminal status of one patient, but not the other. For the latter patient and his
wife, a pregnancy was achieved by testicular sperm extraction (TESE) and
intracytoplasmic sperm injection (ICSI) following genetic counseling. It is
important to investigate genotyping and to classify patients on the basis of
genotypic information in order to arrive at better treatment strategies for male
infertility; especially in counseling of TESE-ICSI.
PMID- 17033938
TI - Adaptations to oxidative stress induced by vitamin E deficiency in rat liver.
AB - Vitamin E deficiency in rats led to a sequence of antioxidant defense adaptations
in the liver. After three weeks, alpha-tocopherol concentration was 5% of
control, but ascorbate and ubiquinol concentrations were 2- to 3-fold greater
than control. During the early phase of adaptation no differences in markers of
lipid peroxidation were observed, but the activities of both cytochrome b5
reductase and glucose-6-phosphate dehydrogenase were significantly greater in
deficient livers. By nine weeks, accumulation of lipid peroxidation end products
began to occur along with declining concentrations of ascorbate, and higher NQO1
activities. At twelve weeks, rat growth ceased, and both lipid peroxidation
products and cytosolic calcium-independent phospholipase A2 reached maximum
concentrations. Thus, in growing rats the changes progressed from increases in
both ubiquinol and quinone reductases through accumulation of lipid peroxidation
products and loss of endogenous antioxidants to finally induction of lipid
metabolizing enzymes and cessation of rat growth.
PMID- 17033939
TI - PRUNE and NM23-M1 expression in embryonic and adult mouse brain.
AB - A genetic interaction between PRUNE and NM23/NDPK has been postulated in
Drosophila melanogaster. Many have focused on Drosophila for the genetic
combination between PRUNE "knock down" and AWD/NM23 fly mutants bearing the P97S
mutation (K-pn, Killer of PRUNE mutation). We postulated a role for PRUNE-NM23
interactions in vertebrate development, demonstrating a physical interaction
between the human PRUNE and NM23-H1 proteins, and partially characterizing their
functional significance in cancer progression. Here, we present an initial
analysis towards the functional characterization of the PRUNE-NM23 interaction
during mammalian embryogenesis. Our working hypothesis is that PRUNE, NM23-H1 and
their protein-protein interaction partners have important roles in mammalian
brain development and adult brain function. Detailed expression analyses from
early mouse brain development to adulthood show significant co-expression of
these two genes during embryonic stages of brain development, especially focusing
on the cortex, hippocampus, midbrain and cerebellum. We hypothesize that their
abnormal expression results in an altered pathway of activation, influencing
protein complex formation and its protein partner interactions in early
embryogenesis. In the adult brain, their function appears concentrated towards
their enzyme activities, wherein biochemical variations can result in brain
dysfunction.
PMID- 17033940
TI - Telephone-delivered interventions for people living with HIV/AIDS: guest
editorial.
PMID- 17033942
TI - Acute scrotum in a neonate.
PMID- 17033943
TI - Acute appendicitis: sonographic evaluation.
PMID- 17033944
TI - How European has "Ultrasound in Medicine" become?
PMID- 17033945
TI - Transcutaneous contrast enhanced sonography of the chest for evaluation of
pleural based pulmonary lesions: experience in 137 patients.
AB - PURPOSE: Transcutaneous ultrasound enables visualization of pleural based lesions
but with a poor correlation to specific pathology. Ultrasound contrast agents in
conjunction with contrast specific imaging techniques are increasingly accepted
in clinical use. Up to date there are no data about the use of contrast enhanced
sonography (CES) in a large series of pleural based pulmonary lesions. MATERIALS
AND METHODS: From August 2004 to August 2005, 137 consecutive patients with
pleural based pulmonary lesions on B-mode sonography were studied by CES using a
transcapillary second-generation contrast agent (SonoVue(R)). The following CES
parameters were retrospectively evaluated. Time to enhancement (TE) of contrast
agent after i. v. application was determined and classified as short TE (< = 6
sec) vs. delayed TE (> 6 sec). Extent of enhancement (EE) was evaluated during
the arterial phase (2 - 30 sec) and the parenchymal phase (1 - 5 minutes) by
using the normal splenic tissue as an in vivo reference, and classified in
reduced EE (anechoic/hypoechoic) vs. marked EE (isoechoic/hyperechoic) during
both phases. Homogeneity of enhancement (HE) was classified as homogeneous vs.
inhomogeneous. 60 patients had histologically confirmed malignant lesions due to
central lung cancer (n = 31), and peripheral malignant lesions (n = 29). 77
patients had benign pleural based lesions including pneumonia (n = 32), pulmonary
embolism (n = 20), compression atelectasis (17), and other benign pleural based
lesions (n = 8). RESULTS: Malignant and benign lesions did not vary significantly
regarding TE, EE, and HE. However, there were highly significant differences in
the ratio of short vs. delayed TE and reduced vs. marked EE between the six
disease groups. Characteristic patterns were short TE with marked EE in all
compression atelectasis cases and in 62 % of patients with pneumonia. Delayed TE
and reduced EE was seen in all patients with pulmonary embolism and in 62 % of
patients with peripheral malignant lesions. Central lung cancer and benign
nodules did not present with such specific patterns. No significant differences
in HE were seen between subgroups. CONCLUSION: Pulmonary lesions are
characterized by different CES-patterns of arterial supply as evidenced by TE and
EE which depends on underlying causes, but CES does not allow to distinguish
benign from malignant pleural based lesions in general.
PMID- 17033946
TI - [Low-MI-sonography with the contrast-agent SonoVue in the diagnosis of infarction
of the spleen, kidney, liver and pancreas].
AB - PURPOSE: The diagnosis of ischemic injury by B-mode-sonography is difficult in
many cases. Aim of the pilot-study was to evaluate whether additional examination
with the ultrasound contrast agent SonoVue could improve the sonographic
diagnosis of ischemic injury. MATERIALS AND METHODS: In a prospective study,
intra-abdominal organs (n = 12) with ischemic lesions found by CT-scan were
examined. All ischemic organs were examined by native B-mode-sonography and after
injection of 1.2 ml SonoVue i. v. The SonoVue-examinations were performed using
the CPS-software (Siemens, Erlangen). RESULTS: Native B-mode-sonography detected
demarcation of ischemic lesions in only 7 of the 12 organs. In contrast, SonoVue
enhanced sonography diagnosed ischemic lesions in all organs. In one patient with
renal infarction, however, the ischemic lesion found by SonoVue-enhanced
sonography was smaller compared with the CT-scan. The diagnosis "compatible with
ischemia" as cause for the abnormalities in B-mode sonography was described in
only 3 out of 12 organs, and none of the organs were classified as "definite
diagnosis of ischemia". In contrast, the diagnosis "definite diagnosis of
ischemia" was made in 10 of the 12 organs when examined with SonoVue-enhanced
sonography. In two further patients, the lesion was classified as "compatible
with ischemia". In these patients, the diagnosis of ischemia was verified by CT
scan, due to the accompanying subtotal splenic infarction and a partial
thrombosis of the coeliac trunc. CONCLUSION: It became evident that SonoVue
enhanced sonography was more sensitive in the diagnosis of ischemic injury than
native B-mode sonography.
PMID- 17033947
TI - 3D ultrasound examination of the superficial lymph nodes--does it provide
additional information?
AB - PURPOSE: To compare the appearance of superficial lymph nodes on standard two
dimensional (2D) ultrasound examination and on three-dimensional (3D) ultrasound
examination. MATERIALS AND METHODS: Fifty two lymph nodes (35 cervical, 16
axillary, 1 inguinal) in 52 patients were examined with ultrasound in 3D mode. In
standard 2D grey-scale examination and on a C-plane of 3D mode (parallel to the
surface of the probe), the shape of a lymph node and its hilum were assessed.
Final histopathological diagnoses included 36 lymphomas, 11 reactive or
inflammatory lymph nodes, 3 metastases and 2 plasmocytoma infiltrations. RESULTS:
The appearance of hilums and lymph nodes as a whole changed on a C-plane of 3D
mode (as compared with 2D presentation) in 28 % and 37 %, respectively. The
differences in lymph node shape on 2D and 3D ultrasound were apparent in a
comparable percentage of reactive lymph nodes (45 %) and lymphomatous lymph nodes
(39 %). The differences in lymph node hilum shape on 2D and 3D ultrasound applied
to 56 % of reactive lymph nodes and 20 % of lymphomatous lymph nodes. CONCLUSION:
Three-dimensional imaging on a C-plane (parallel to the surface of the probe) may
supply the examiner with different information concerning the shape of the lymph
node and its hilum in comparison to standard 2D ultrasound. Changes in the shapes
of hilum and lymph node occurred in reactive or inflamed lymph nodes as well as
in lymphomas. Clinical significance of this fact demands further investigation.
PMID- 17033956
TI - Nucleotide-resolution mapping of topoisomerase-mediated and apoptotic DNA strand
scissions at or near an MLL translocation hotspot.
AB - The emergence of therapy-related acute myeloid leukemia (t-AML) has been
associated with DNA topoisomerase II (TOP2)-targeted drug treatments and
chromosomal translocations frequently involving the MLL, or ALL-1, gene. Two
distinct mechanisms have been implicated as potential triggers of t-AML
translocations: TOP2-mediated DNA cleavage and apoptotic higher-order chromatin
fragmentation. Assessment of the role of TOP2 in this process has been hampered
by a lack of techniques allowing in vivo mapping of TOP2-mediated DNA cleavage at
nucleotide resolution in single-copy genes. A novel method, extension ligation
mediated polymerase chain reaction (ELMPCR), was used here for mapping
topoisomerase-mediated DNA strand breaks and apoptotic DNA cleavage across a
translocation-prone region of MLL in human cells. We report the first genomic map
integrating translocation breakpoints and topoisomerase I, TOP2, and apoptotic
DNA cleavage sites at nucleotide resolution across an MLL region harboring a t
AML translocation hotspot. This hotspot is flanked by a TOP2 cleavage site and is
localized at one extremity of a minor apoptotic cleavage region, where multiple
single- and double-strand breaks were induced by caspase-activated apoptotic
nucleases. This cleavage pattern was in sharp contrast to that observed
approximately 200 bp downstream in the exon 12 region, which displayed much
stronger apoptotic cleavage but where no double-strand breaks were detected and
no t-AML-associated breakpoints were reported. The localization and remarkable
clustering of the t-AML breakpoints cannot be explained simply by the DNA
cleavage patterns but might result from potential interactions between TOP2
poisoning, apoptotic DNA cleavage, and DNA repair attempts at specific sites of
higher-order chromatin structure in apoptosis-evading cells. ELMPCR provides a
new tool for investigating the role of DNA topoisomerases in fundamental genetic
processes and translocations associated with cancer treatments involving
topoisomerase-targeted drugs.
PMID- 17033957
TI - Generalized genomic distance-based regression methodology for multilocus
association analysis.
AB - Large-scale, multilocus genetic association studies require powerful and
appropriate statistical-analysis tools that are designed to relate genotype and
haplotype information to phenotypes of interest. Many analysis approaches
consider relating allelic, haplotypic, or genotypic information to a trait
through use of extensions of traditional analysis techniques, such as contingency
table analysis, regression methods, and analysis-of-variance techniques. In this
work, we consider a complementary approach that involves the characterization and
measurement of the similarity and dissimilarity of the allelic composition of a
set of individuals' diploid genomes at multiple loci in the regions of interest.
We describe a regression method that can be used to relate variation in the
measure of genomic dissimilarity (or "distance") among a set of individuals to
variation in their trait values. Weighting factors associated with functional or
evolutionary conservation information of the loci can be used in the assessment
of similarity. The proposed method is very flexible and is easily extended to
complex multilocus-analysis settings involving covariates. In addition, the
proposed method actually encompasses both single-locus and haplotype-phylogeny
analysis methods, which are two of the most widely used approaches in genetic
association analysis. We showcase the method with data described in the
literature. Ultimately, our method is appropriate for high-dimensional genomic
data and anticipates an era when cost-effective exhaustive DNA sequence data can
be obtained for a large number of individuals, over and above genotype
information focused on a few well-chosen loci.
PMID- 17033958
TI - Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).
AB - Mucopolysaccharidosis IIIC (MPS IIIC, or Sanfilippo C syndrome) is a lysosomal
storage disorder caused by the inherited deficiency of the lysosomal membrane
enzyme acetyl-coenzyme A: alpha -glucosaminide N-acetyltransferase (N
acetyltransferase), which leads to impaired degradation of heparan sulfate. We
report the narrowing of the candidate region to a 2.6-cM interval between D8S1051
and D8S1831 and the identification of the transmembrane protein 76 gene (TMEM76),
which encodes a 73-kDa protein with predicted multiple transmembrane domains and
glycosylation sites, as the gene that causes MPS IIIC when it is mutated. Four
nonsense mutations, 3 frameshift mutations due to deletions or a duplication, 6
splice-site mutations, and 14 missense mutations were identified among 30
probands with MPS IIIC. Functional expression of human TMEM76 and the mouse
ortholog demonstrates that it is the gene that encodes the lysosomal N
acetyltransferase and suggests that this enzyme belongs to a new structural class
of proteins that transport the activated acetyl residues across the cell
membrane.
PMID- 17033960
TI - Test for interaction between two unlinked loci.
AB - Despite the growing consensus on the importance of testing gene-gene interactions
in genetic studies of complex diseases, the effect of gene-gene interactions has
often been defined as a deviance from genetic additive effects, which is
essentially treated as a residual term in genetic analysis and leads to low power
in detecting the presence of interacting effects. To what extent the definition
of gene-gene interaction at population level reflects the genes' biochemical or
physiological interaction remains a mystery. In this article, we introduce a
novel definition and a new measure of gene-gene interaction between two unlinked
loci (or genes). We developed a general theory for studying linkage
disequilibrium (LD) patterns in disease population under two-locus disease
models. The properties of using the LD measure in a disease population as a
function of the measure of gene-gene interaction between two unlinked loci were
also investigated. We examined how interaction between two loci creates LD in a
disease population and showed that the mathematical formulation of the new
definition for gene-gene interaction between two loci was similar to that of the
LD between two loci. This finding motived us to develop an LD-based statistic to
detect gene-gene interaction between two unlinked loci. The null distribution and
type I error rates of the LD-based statistic for testing gene-gene interaction
were validated using extensive simulation studies. We found that the new test
statistic was more powerful than the traditional logistic regression under three
two-locus disease models and demonstrated that the power of the test statistic
depends on the measure of gene-gene interaction. We also investigated the impact
of using tagging SNPs for testing interaction on the power to detect interaction
between two unlinked loci. Finally, to evaluate the performance of our new
method, we applied the LD-based statistic to two published data sets. Our results
showed that the P values of the LD-based statistic were smaller than those
obtained by other approaches, including logistic regression models.
PMID- 17033959
TI - Molecular population genetics of the gene encoding the human fertilization
protein zonadhesin reveals rapid adaptive evolution.
AB - A hallmark of positive selection (adaptive evolution) in protein-coding regions
is a d(N)/d(S) ratio >1, where d(N) is the number of nonsynonymous
substitutions/nonsynonymous sites and d(S) is the number of synonymous
substitutions/synonymous sites. Zonadhesin is a male reproductive protein
localized on the sperm head, comprising many domains known to be involved in cell
cell interaction or cell adhesion. Previous studies have shown that VWD domains
(homologous to the D domains of the von Willebrand factor) are involved directly
in binding to the female zona pellucida (ZP) in a species-specific manner. In
this study, we sequenced 47 coding exons in 12 primate species and, by using
maximum-likelihood methods to determine sites under positive selection, we show
that VWD2, membrane/A5 antigen mu receptor, and mucin-like domains in zonadhesin
are rapidly evolving and, thus, may be involved in binding to the ZP in a species
specific manner in primates. In addition, polymorphism data from 48 human
individuals revealed significant polymorphism-to-divergence heterogeneity and a
significant departure from equilibrium-neutral expectations in the frequency
spectrum, suggesting balancing selection and positive selection occurring in
zonadhesin (ZAN) within human populations. Finally, we observe adaptive evolution
in haplotypes segregating for a frameshift mutation that was previously thought
to indicate that ZAN was a potential pseudogene.
PMID- 17033961
TI - Multipoint linkage analysis with many multiallelic or dense diallelic markers:
Markov chain-Monte Carlo provides practical approaches for genome scans on
general pedigrees.
AB - Computations for genome scans need to adapt to the increasing use of dense
diallelic markers as well as of full-chromosome multipoint linkage analysis with
either diallelic or multiallelic markers. Whereas suitable exact-computation
tools are available for use with small pedigrees, equivalent exact computation
for larger pedigrees remains infeasible. Markov chain-Monte Carlo (MCMC)-based
methods currently provide the only computationally practical option. To date, no
systematic comparison of the performance of MCMC-based programs is available, nor
have these programs been systematically evaluated for use with dense diallelic
markers. Using simulated data, we evaluate the performance of two MCMC-based
linkage-analysis programs--lm_markers from the MORGAN package and SimWalk2--under
a variety of analysis conditions. Pedigrees consisted of 14, 52, or 98
individuals in 3, 5, or 6 generations, respectively, with increasing amounts of
missing data in larger pedigrees. One hundred replicates of markers and trait
data were simulated on a 100-cM chromosome, with up to 10 multiallelic and up to
200 diallelic markers used simultaneously for computation of multipoint LOD
scores. Exact computation was available for comparison in most situations, and
comparison with a perfectly informative marker or interprogram comparison was
available in the remaining situations. Our results confirm the accuracy of both
programs in multipoint analysis with multiallelic markers on pedigrees of varied
sizes and missing-data patterns, but there are some computational differences. In
contrast, for large numbers of dense diallelic markers, only the lm_markers
program was able to provide accurate results within a computationally practical
time. Thus, programs in the MORGAN package are the first available to provide a
computationally practical option for accurate linkage analyses in genome scans
with both large numbers of diallelic markers and large pedigrees.
PMID- 17033962
TI - Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies.
AB - Epigenetic regulation of gene expression is a source of genetic variation, which
can mimic recessive mutations by creating transcriptional haploinsufficiency.
Germline epimutations and genomic imprinting are typical examples, although their
existence can be difficult to reveal. Genomic imprinting can be tissue specific,
with biallelic expression in some tissues and monoallelic expression in others or
with polymorphic expression in the general population. Mutations in the skeletal
muscle ryanodine-receptor gene (RYR1) are associated with malignant hyperthermia
susceptibility and the congenital myopathies central core disease and
multiminicore disease. RYR1 has never been thought to be affected by epigenetic
regulation. However, during the RYR1-mutation analysis of a cohort of patients
with recessive core myopathies, we discovered that 6 (55%) of 11 patients had
monoallelic RYR1 transcription in skeletal muscle, despite being heterozygous at
the genomic level. In families for which parental DNA was available, segregation
studies showed that the nonexpressed allele was maternally inherited.
Transcription analysis in patients' fibroblasts and lymphoblastoid cell lines
indicated biallelic expression, which suggests tissue-specific silencing.
Transcription analysis of normal human fetal tissues showed that RYR1 was
monoallelically expressed in skeletal and smooth muscles, brain, and eye in 10%
of cases. In contrast, 25 normal adult human skeletal-muscle samples displayed
only biallelic expression. Finally, the administration of the DNA
methyltransferase inhibitor 5-aza-deoxycytidine to cultured patient skeletal
muscle myoblasts reactivated the transcription of the silenced allele, which
suggests hypermethylation as a mechanism for RYR1 silencing. Our data indicate
that RYR1 undergoes polymorphic, tissue-specific, and developmentally regulated
allele silencing and that this unveils recessive mutations in patients with core
myopathies. Furthermore, our data suggest that imprinting is a likely mechanism
for this phenomenon and that similar mechanisms could play a role in human
phenotypic heterogeneity.
PMID- 17033963
TI - Distinct clinical phenotypes associated with a mutation in the mitochondrial
translation elongation factor EFTs.
AB - The 13 polypeptides encoded in mitochondrial DNA (mtDNA) are synthesized in the
mitochondrial matrix on a dedicated protein-translation apparatus that resembles
that found in prokaryotes. Here, we have investigated the genetic basis for a
mitochondrial protein-synthesis defect associated with a combined oxidative
phosphorylation enzyme deficiency in two patients, one of whom presented with
encephalomyopathy and the other with hypertrophic cardiomyopathy. Sequencing of
candidate genes revealed the same homozygous mutation (C997T) in both patients in
TSFM, a gene coding for the mitochondrial translation elongation factor EFTs.
EFTs functions as a guanine nucleotide exchange factor for EFTu, another
translation elongation factor that brings aminoacylated transfer RNAs to the
ribosomal A site as a ternary complex with guanosine triphosphate. The mutation
predicts an Arg333Trp substitution at an evolutionarily conserved site in a
subdomain of EFTs that interacts with EFTu. Molecular modeling showed that the
substitution disrupts local subdomain structure and the dimerization interface.
The steady-state levels of EFTs and EFTu in patient fibroblasts were reduced by
75% and 60%, respectively, and the amounts of assembled complexes I, IV, and V
were reduced by 35%-91% compared with the amounts in controls. These phenotypes
and the translation defect were rescued by retroviral expression of either EFTs
or EFTu. These data clearly establish mutant EFTs as the cause of disease in
these patients. The fact that the same mutation is associated with distinct
clinical phenotypes suggests the presence of genetic modifiers of the
mitochondrial translation apparatus.
PMID- 17033964
TI - Mutations of the mitochondrial holocytochrome c-type synthase in X-linked
dominant microphthalmia with linear skin defects syndrome.
AB - The microphthalmia with linear skin defects syndrome (MLS, or MIDAS) is an X
linked dominant male-lethal disorder almost invariably associated with segmental
monosomy of the Xp22 region. In two female patients, from two families, with MLS
and a normal karyotype, we identified heterozygous de novo point mutations--a
missense mutation (p.R217C) and a nonsense mutation (p.R197X)--in the HCCS gene.
HCCS encodes the mitochondrial holocytochrome c-type synthase that functions as
heme lyase by covalently adding the prosthetic heme group to both apocytochrome c
and c(1). We investigated a third family, displaying phenotypic variability, in
which the mother and two of her daughters carry an 8.6-kb submicroscopic deletion
encompassing part of the HCCS gene. Functional analysis demonstrates that both
mutant proteins (R217C and Delta 197-268) were unable to complement a
Saccharomyces cerevisiae mutant deficient for the HCCS orthologue Cyc3p, in
contrast to wild-type HCCS. Moreover, ectopically expressed HCCS wild-type and
the R217C mutant protein are targeted to mitochondria in CHO-K1 cells, whereas
the C-terminal-truncated Delta 197-268 mutant failed to be sorted to
mitochondria. Cytochrome c, the final product of holocytochrome c-type synthase
activity, is implicated in both oxidative phosphorylation (OXPHOS) and apoptosis.
We hypothesize that the inability of HCCS-deficient cells to undergo cytochrome c
mediated apoptosis may push cell death toward necrosis that gives rise to severe
deterioration of the affected tissues. In summary, we suggest that disturbance of
both OXPHOS and the balance between apoptosis and necrosis, as well as the X
inactivation pattern, may contribute to the variable phenotype observed in
patients with MLS.
PMID- 17033965
TI - A chromosomal rearrangement hotspot can be identified from population genetic
variation and is coincident with a hotspot for allelic recombination.
AB - Insights into the origins of structural variation and the mutational mechanisms
underlying genomic disorders would be greatly improved by a genomewide map of
hotspots of nonallelic homologous recombination (NAHR). Moreover, our
understanding of sequence variation within the duplicated sequences that are
substrates for NAHR lags far behind that of sequence variation within the single
copy portion of the genome. Perhaps the best-characterized NAHR hotspot lies
within the 24-kb-long Charcot-Marie-Tooth disease type 1A (CMT1A)-repeats (REPs)
that sponsor deletions and duplications that cause peripheral neuropathies. We
investigated structural and sequence diversity within the CMT1A-REPs, both within
and between species. We discovered a high frequency of retroelement insertions,
accelerated sequence evolution after duplication, extensive paralogous gene
conversion, and a greater than twofold enrichment of SNPs in humans relative to
the genome average. We identified an allelic recombination hotspot underlying the
known NAHR hotspot, which suggests that the two processes are intimately related.
Finally, we used our data to develop a novel method for inferring the location of
an NAHR hotspot from sequence variation within segmental duplications and applied
it to identify a putative NAHR hotspot within the LCR22 repeats that sponsor
velocardiofacial syndrome deletions. We propose that a large-scale project to map
sequence variation within segmental duplications would reveal a wealth of novel
chromosomal-rearrangement hotspots.
PMID- 17033966
TI - Analysis of high-resolution HapMap of DTNBP1 (Dysbindin) suggests no consistency
between reported common variant associations and schizophrenia.
AB - DTNBP1 was first identified as a putative schizophrenia-susceptibility gene in
Irish pedigrees, with a report of association to common genetic variation.
Several replication studies have reported confirmation of an association to
DTNBP1 in independent European samples; however, reported risk alleles and
haplotypes appear to differ between studies, and comparison among studies has
been confounded because different marker sets were employed by each group. To
facilitate evaluation of existing evidence of association and further work, we
supplemented the extensive genotype data, available through the International
HapMap Project (HapMap), about DTNBP1 by specifically typing all associated
single-nucleotide polymorphisms reported in each of the studies of the Centre
d'Etude du Polymorphisme Humain (CEPH)-derived HapMap sample (CEU). Using this
high-density reference map, we compared the putative disease-associated haplotype
from each study and found that the association studies are inconsistent with
regard to the identity of the disease-associated haplotype at DTNBP1.
Specifically, all five "replication" studies define a positively associated
haplotype that is different from the association originally reported. We further
demonstrate that, in all six studies, the European-derived populations studied
have haplotype patterns and frequencies that are consistent with HapMap CEU
samples (and each other). Thus, it is unlikely that population differences are
creating the inconsistency of the association studies. Evidence of association
is, at present, equivocal and unsatisfactory. The new dense map of the region may
be valuable in more-comprehensive follow-up studies.
PMID- 17033967
TI - Mapping trait loci by use of inferred ancestral recombination graphs.
AB - Large-scale association studies are being undertaken with the hope of uncovering
the genetic determinants of complex disease. We describe a computationally
efficient method for inferring genealogies from population genotype data and show
how these genealogies can be used to fine map disease loci and interpret
association signals. These genealogies take the form of the ancestral
recombination graph (ARG). The ARG defines a genealogical tree for each locus,
and, as one moves along the chromosome, the topologies of consecutive trees shift
according to the impact of historical recombination events. There are two stages
to our analysis. First, we infer plausible ARGs, using a heuristic algorithm,
which can handle unphased and missing data and is fast enough to be applied to
large-scale studies. Second, we test the genealogical tree at each locus for a
clustering of the disease cases beneath a branch, suggesting that a causative
mutation occurred on that branch. Since the true ARG is unknown, we average this
analysis over an ensemble of inferred ARGs. We have characterized the performance
of our method across a wide range of simulated disease models. Compared with
simpler tests, our method gives increased accuracy in positioning untyped
causative loci and can also be used to estimate the frequencies of untyped
causative alleles. We have applied our method to Ueda et al.'s association study
of CTLA4 and Graves disease, showing how it can be used to dissect the
association signal, giving potentially interesting results of allelic
heterogeneity and interaction. Similar approaches analyzing an ensemble of ARGs
inferred using our method may be applicable to many other problems of inference
from population genotype data.
PMID- 17033968
TI - Mutation-positive and mutation-negative patients with Cowden and Bannayan-Riley
Ruvalcaba syndromes associated with distinct 10q haplotypes.
AB - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) encodes a tumor
suppressor phosphatase frequently mutated in both sporadic and heritable forms of
human cancer. Germline mutations are associated with a number of heritable cancer
syndromes that are jointly referred to as the "PTEN hamartoma tumor syndrome"
(PHTS) and include Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus
syndrome, and Proteus-like syndrome. Germline PTEN mutations have been identified
in a significant proportion of patients with PHTS; however, there are still many
individuals with classic diagnostic features for whom mutations have yet to be
identified. To address this, we took a haplotype-based approach and investigated
the association of specific genomic regions of the PTEN locus with PHTS. We found
this locus to be characterized by three distinct haplotype blocks 33 kb, 65 kb,
and 43 kb in length. Comparisons of the haplotype distributions for all three
blocks differed significantly among patients with PHTS and controls (P=.0098,
P<.0001, and P<.0001 for blocks 1, 2, and 3, respectively). "Rare" haplotype
blocks and extended haplotypes account for two-to-threefold more PHTS chromosomes
than control chromosomes. PTEN mutation-negative patients are strongly associated
with a haplotype block spanning a region upstream of PTEN and the gene's first
intron (P=.0027). Furthermore, allelic combinations contribute to the phenotypic
complexity of this syndrome. Taken together, these data suggest that specific
haplotypes and rare alleles underlie the disease etiology in these sample
populations; constitute low-penetrance, modifying loci; and, specifically in the
case of patients with PHTS for whom traditional mutations have yet to be
identified, may harbor pathogenic variant(s) that have escaped detection by
standard PTEN mutation-scanning methodologies.
PMID- 17033969
TI - A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss
(CATSHL) syndrome.
AB - Activating mutations of FGFR3, a negative regulator of bone growth, are well
known to cause a variety of short-limbed bone dysplasias and craniosynostosis
syndromes. We mapped the locus causing a novel disorder characterized by
camptodactyly, tall stature, scoliosis, and hearing loss (CATSHL syndrome) to
chromosome 4p. Because this syndrome recapitulated the phenotype of the Fgfr3
knockout mouse, we screened FGFR3 and subsequently identified a heterozygous
missense mutation that is predicted to cause a p.R621H substitution in the
tyrosine kinase domain and partial loss of FGFR3 function. These findings
indicate that abnormal FGFR3 signaling can cause human anomalies by promoting as
well as inhibiting endochondral bone growth.
PMID- 17033970
TI - PLA2G6 mutation underlies infantile neuroaxonal dystrophy.
AB - Infantile neuroaxonal dystrophy (INAD) is an autosomal recessive progressive
neurodegenerative disease that presents within the first 2 years of life and
culminates in death by age 10 years. Affected individuals from two unrelated
Bedouin Israeli kindreds were studied. Brain imaging demonstrated diffuse
cerebellar atrophy and abnormal iron deposition in the medial and lateral globus
pallidum. Progressive white-matter disease and reduction of the N-acetyl
aspartate : chromium ratio were evident on magnetic resonance spectroscopy,
suggesting loss of myelination. The clinical and radiological diagnosis of INAD
was verified by sural nerve biopsy. The disease gene was mapped to a 1.17-Mb
locus on chromosome 22q13.1 (LOD score 4.7 at recombination fraction 0 for SNP
rs139897), and an underlying mutation common to both affected families was
identified in PLA2G6, the gene encoding phospholipase A2 group VI (cytosolic,
calcium-independent). These findings highlight a role of phospholipase in
neurodegenerative disorders.
PMID- 17033971
TI - Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with
renal magnesium wasting, renal failure, and severe ocular involvement.
AB - Claudins are major components of tight junctions and contribute to the epithelial
barrier function by restricting free diffusion of solutes through the
paracellular pathway. We have mapped a new locus for recessive renal magnesium
loss on chromosome 1p34.2 and have identified mutations in CLDN19, a member of
the claudin multigene family, in patients affected by hypomagnesemia, renal
failure, and severe ocular abnormalities. CLDN19 encodes the tight-junction
protein claudin-19, and we demonstrate high expression of CLDN19 in renal tubules
and the retina. The identified mutations interfere severely with either cell
membrane trafficking or the assembly of the claudin-19 protein. The
identification of CLDN19 mutations in patients with chronic renal failure and
severe visual impairment supports the fundamental role of claudin-19 for normal
renal tubular function and undisturbed organization and development of the
retina.
PMID- 17033972
TI - Detecting disease-causing mutations in the human genome by haplotype matching.
AB - Comparisons between haplotypes from affected patients and the human reference
genome are frequently used to identify candidates for disease-causing mutations,
even though these alignments are expected to reveal a high level of background
neutral polymorphism. This limits the scope of genetic studies to relatively
small genomic intervals, because current methods for distinguishing potential
causal mutations from neutral variation are inefficient. Here we describe a new
strategy for detecting mutations that is based on comparing affected haplotypes
with closely matched control sequences from healthy individuals, rather than with
the human reference genome. We use theory, simulation, and a real data set to
show that this approach is expected to reduce the number of sequence variants
that must be subjected to follow-up analysis by at least a factor of 20 when
closely matched control sequences are selected from a reference panel with as few
as 100 control genomes. We also define a reference data resource that would allow
efficient application of this strategy to large critical intervals across the
genome.
PMID- 17033973
TI - Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia.
AB - Mutations in FOXP2 cause developmental verbal dyspraxia (DVD), but only a few
cases have been described. We characterize 13 patients with DVD--5 with
hemizygous paternal deletions spanning the FOXP2 gene, 1 with a translocation
interrupting FOXP2, and the remaining 7 with maternal uniparental disomy of
chromosome 7 (UPD7), who were also given a diagnosis of Silver-Russell Syndrome
(SRS). Of these individuals with DVD, all 12 for whom parental DNA was available
showed absence of a paternal copy of FOXP2. Five other individuals with deletions
of paternally inherited FOXP2 but with incomplete clinical information or
phenotypes too complex to properly assess are also described. Four of the
patients with DVD also meet criteria for autism spectrum disorder. Individuals
with paternal UPD7 or with partial maternal UPD7 or deletion starting downstream
of FOXP2 do not have DVD. Using quantitative real-time polymerase chain reaction,
we show the maternally inherited FOXP2 to be comparatively underexpressed. Our
results indicate that absence of paternal FOXP2 is the cause of DVD in patients
with SRS with maternal UPD7. The data also point to a role for differential
parent-of-origin expression of FOXP2 in human speech development.
PMID- 17033974
TI - Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal
recessive cone dystrophy.
AB - Retinal signal transmission depends on the activity of high voltage-gated l-type
calcium channels in photoreceptor ribbon synapses. We recently identified a
truncating frameshift mutation in the Cacna2d4 gene in a spontaneous mouse mutant
with profound loss of retinal signaling and an abnormal morphology of ribbon
synapses in rods and cones. The Cacna2d4 gene encodes an l-type calcium-channel
auxiliary subunit of the alpha (2) delta type. Mutations in its human orthologue,
CACNA2D4, were not yet known to be associated with a disease. We performed
mutation analyses of 34 patients who received an initial diagnosis of night
blindness, and, in two affected siblings, we detected a homozygous nucleotide
substitution (c.2406C-->A) in CACNA2D4. The mutation introduces a premature stop
codon that truncates one-third of the corresponding open reading frame. Both
patients share symptoms of slowly progressing cone dystrophy. These findings
represent the first report of a mutation in the human CACNA2D4 gene and define a
novel gene defect that causes autosomal recessive cone dystrophy.
PMID- 17033976
TI - [Retrospective comparative analysis of antidementia medication persistence
patterns in Spanish Alzheimer's disease patients treated with donepezil,
rivastigmine, galantamine and memantine].
AB - INTRODUCTION AND AIM: Dementia of Alzheimer type has become the most frequent
type of dementia in our environment. Treatment persistence is a crucial factor to
delay patient functional and cognitive impairment. The aim of the present study
was to determine treatment persistence in usual care settings with four different
antidementia drugs: donepezil, rivastigmine, galantamine and memantine in a
cohort of patients with Alzheimer's dementia in Spain. PATIENTS AND METHODS: An
Alzheimer type dementia retrospective cohort study was performed in 13 Primary
Care Health Centers in Spain. The study included patients treated between January
2000 and March 2005. RESULTS: A total of 299 patients (44.8% female), mean age
77.9 years, were included: 101 donepezil (33.8.%), 105 rivastigmine (35.1%), 51
galantamine (17.1%) and 42 memantine (14.0%). Mean treatment duration was
significantly different depending on therapy type, showing higher values for
donepezil patients (mean: 83.3 weeks; 95% CI: 72.7-93.9) than for the other
cholinesterase inhibitors: rivastigmine (mean: 76.6 weeks; 95% CI: 66.0-87.3),
galantamine (mean: 65.8 weeks; 95% CI: 55.3-76.3) and memantine (60.9 weeks; 95%
CI: 48.8-73.1), p = 0.049. Overall treatment persistence was significantly
different between drugs, with again donepezil showing higher persistence (median
time: 70.3 weeks; 95% CI: 49.8-90.7) than with the others drugs: rivastigmine
(median time: 56.1 weeks; 95% CI: 36.1-76.2), galantamine (median time: 56.7
weeks; 95% CI: 41.1-72.3) and memantine (median time: 52.1 weeks; 95% CI: 35.2
69.1), log-rank = 10.16; p = 0.017. CONCLUSION: This study showed significative
differences in the global treatment persistence among the considered drug
cholinesterase inhibitors, showing higher persistence resulting in patients
treated with donepezil compared to those who received rivastigmine, galantamine
or memantine.
PMID- 17033975
TI - Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with
mutations in the desmosomal gene desmocollin-2.
AB - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an
inherited myocardial disorder associated with arrhythmias, heart failure, and
sudden death. To date, mutations in four genes encoding major desmosomal proteins
(plakoglobin, desmoplakin, plakophilin-2, and desmoglein-2) have been implicated
in the pathogenesis of ARVD/C. We screened 77 probands with ARVD/C for mutations
in desmocollin-2 (DSC2), a gene coding for a desmosomal cadherin. Two
heterozygous mutations--a deletion and an insertion--were identified in four
probands. Both mutations result in frameshifts and premature truncation of the
desmocollin-2 protein. For the first time, we have identified mutations in
desmocollin-2 in patients with ARVD/C, a finding that is consistent with the
hypothesis that ARVD/C is a disease of the desmosome.
PMID- 17033977
TI - [Internal structure of Dysfunctional Beliefs and Attitudes about Sleep Scale in a
Spanish shift workers sample].
AB - INTRODUCTION: Dysfunctional beliefs are some of the psychological factors that
explains the origin and maintenance of insomnia. Morin developed a five
theoretical dimension scale, the Dysfunctional Beliefs and Attitudes about Sleep
Scale (DBAS), to assess them. AIMS: To analyze the internal structure of the
Spanish version of DBAS, and to establish the differences on DBAS scores between
two groups above described. SUBJECTS AND METHODS: The sample was 237 workers of
those 197 were shift workers and the rest had a stable timetable (mean age =
43.07; standard deviation = 9.39). The DBAS and the Pittsburgh Sleep Quality
Index was administrated to them. RESULTS: The results of the items analysis and
reliability of each five dimensions were moderate, except for the first and
second dimension of Morin's proposal. Confirmatory factorial analysis isolated
four factors: consequences of the insomnia on the diurnal yield/functioning
(alpha = 0.75); control and prediction of the sleep (alpha = 0.70); consequences
of the insomnia on the physical and mental health (alpha = 0.69), and
expectations on the association sleep-age (alpha = 0.60). It was corroborated
that either first, second or third factor allowed differentiating one group of
another. CONCLUSIONS: All these results allowed us to consider Spanish version of
DBAS as an appropriated 18 items adapted version. The structure of four factors
is theoretically coherent, and it shows an adequate internal consistency and high
capacity to differentiate well from bad sleepers.
PMID- 17033978
TI - [Evaluation of autonomic cardiovascular functioning in patients with syncope].
AB - INTRODUCTION: According to the current literature on the subject, patients with
syncope suffer a dysfunction of the autonomic nervous system (ANS). Yet few
studies offer a clear explanation of this dysfunction. Moreover, the evaluation
of cardiovascular reflexes is a simple, useful method of studying the functional
status of the ANS. This work was designed to evaluate the existence of
dysautonomia in syncope patients by means of the autonomic cardiovascular
stimulation tests; it has been the most comprehensive of those published to date.
SUBJECTS AND METHODS: We studied 170 healthy volunteers and 188 patients with
syncopes in the previous months, paired by age and sex. Cardiovascular
stimulation tests were conducted, in accordance with Ewing and Clark's
methodology, together with the cold test. A rating scale was included to evaluate
the symptoms related to ANS involvement. RESULTS: Syncope patients display lower
reactivity in tests involving cardiovascular stimulation of the ANS, regardless
of whether they are taken individually or as a whole (67% in patients and 39% in
controls) (p = 0.0001), except in the cold test. They also show an increase in
the clinical symptoms of an autonomic origin (2.82 +/- 0.17) with respect to
control subjects (0.78 +/- 0.09) (p = 0.0001). CONCLUSIONS: Our syncope patients
have a dysautonomia that appears as a sympathetic and parasympathetic
hypofunction. These findings confirm the value of autonomic cardiovascular
stimulation tests in the study of these patients. Moreover, the search for other
symptoms of autonomic involvement can be a great aid in evaluating this
pathology.
PMID- 17033979
TI - [Parkinsonism and Camptocormia with focal spinal myopathy: case report and
responsiveness to treatment].
AB - INTRODUCTION: Camptocormia is characterised by extreme flexion of the
thoracolumbar spine. It suffered an increase during walking and it is relieved in
supine position. Camptocormia has been described in psychogenic disorders, but in
other diseases, including Parkinson's disease as well. It has been recently
described several cases with focal spinal myopathy, and we present a patient with
this clinical association. CASE REPORT: This 82-year-old man had a 6-year history
of parkinsonian symptoms, mostly of rigid-akinetic type. He was in stage 4 on
Hoehn & Yahr scale, and he had reached 62 points on Unified Parkinson Disease
Rating Scale. Over the past 6-8 months, he developed progressive forward flexion
of the trunk with clinical features of camptocormia. He suffered flogotic
symptoms and signs on her lower back, and there were no dystonic posture or
clinical features. Lumbar computerised tomography showed fat replacement of the
paravertebral L3 muscles. A surgical paravertebral muscle examination and biopsy
were performed, showing diffuse fat replacement and only a marginal myopathic
focus. It was made several therapeutic approaches, with levodopa dose increase,
reduction, fractioning, and addition of dopa-agonists. All of these strategies
failed. It was determined to try a steroid course, but there were no improvement,
so physiotherapy and rehabilitation measures did. He finally was confined to
wheelchair. CONCLUSIONS: Physiopathologic and therapeutic aspects of camptocormia
in Parkinson's disease are unclear. Their relationship could be casual or causal.
Patients with clear inflammatory myopathy could benefit from steroid therapy, but
patients with end-stage myopathy probably do not so.
PMID- 17033980
TI - [Hypertrophic cranial and spinal pachymeningitis. A description of four new cases
and a review of the literature].
AB - INTRODUCTION: Hypertrophic pachymeningitis is an infrequent disease that is
characterised by inflammatory hypertrophy of the dura mater. There are cranial,
spinal and craniospinal forms of the disease. They may be due to underlying
infectious, autoimmune or neoplastic processes, although most of the cases
reported in recent years have no base pathology and are known as idiopathic
hypertrophic pachymeningitis. The ideal treatment is unknown, but most cases
usually respond well to therapy with corticoids. CASE REPORTS: We report two
cases of cranial forms, one idiopathic with typical clinical features consisting
in cranial polyneuropathy and good response to corticoids, and another case
secondary to rheumatoid arthritis that began with epileptic seizures. Both had a
parenchymatous oedema. The two forms of spinal pachymeningitis presented as
progressive paraparesis that evolved well after surgical removal of the lesion.
CONCLUSIONS: On observing pachymeningitis in neuroimaging tests it becomes
necessary to conduct a comprehensive aetiological study in search of infectious,
autoimmune and neoplastic diseases. In the cranial forms there may be
parenchymatous oedema, which would explain the epileptic seizures and the
cognitive deterioration of our patients. Response to corticoids is spectacular,
although it is often necessary to continue to administer them for prolonged
periods of time.
PMID- 17033981
TI - [Imidazoline I(2) receptors as a possible marker for malignancy in human glial
cell tumours].
AB - AIM: To present the experimental data that support the hypothesis that the
imidazoline I(2) receptors may be assessed as a biological marker to establish
diagnosis and grade of human gliomas. DEVELOPMENT: Gliomas constitute the most
important group of brain neoplasm in humans. In these tumours accurate
histopathologic diagnosis is a first crucial prerequisite for patient treatment.
However, current grading schemes are still limited by subjective histologic
criteria. Therefore, the search for new molecular and biological markers of
gliomas represents a crucial step. In this context, it has been reported a
significant increase in I(2) density in human gliomas when compared with normal
brain tissue and other intracranial non-glial tumours. Moreover, this increase
seems to fit well with the degree of malignancy in human gliomas. Thus, in
glioblastomas multiformes the I(2) density is 1.4 times higher than in anaplastic
astrocytomas and 2.2 higher than in low-grade astrocytomas. CONCLUSIONS: The
present results demonstrate that the measurement of the I(2) density by positron
emission tomography techniques could be used in the future for grading and
prognosis of human gliomas. This could avoid the current need for tumour biopsies
in order to obtain a histopathologic diagnosis.
PMID- 17033982
TI - [The pathophysiology of migraine. Reflections on the glutamatergic hypothesis].
AB - INTRODUCTION AND DEVELOPMENT: Migraine is an episodic primary headache defined by
its clinical characteristics. Several pathophysiological hypotheses have been put
forward in an attempt to explain the mechanism by which headaches develop in
patients suffering from migraine. We believe that there are enough data available
to consider that in the cerebral cortex, and in certain situations, there may be
either an alteration in the balance of glutamate in the extracellular space or
generation of excitatory post-synaptic potentials at rest based on the activation
of slightly increased AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid) and kainate receptors, which would account for the cortical
hyperexcitability and the interictal changes observed in patients with migraine.
CONCLUSIONS: Further knowledge about the mechanisms that start and trigger
migraines is essential for the development of new therapeutic approaches.
PMID- 17033984
TI - [Effects of bromazepam on motor learning: an electroencephalogram analysis based
on the beta rhythm].
PMID- 17033985
TI - [Fatal massive hemoptysis during thrombolysis of acute ischemic stroke].
PMID- 17033986
TI - [Asymptomatic polymicrogyria].
PMID- 17033987
TI - Sorbents: from bench to bedside. Can we combine membrane separation processes and
adsorbent based solute removal?
PMID- 17033989
TI - Biomaterials surface characterization and modification.
AB - This paper presents several examples of recent work in the field of surface
modification and characterization of biomaterials. Due to the explosion of
techniques and approaches in this area, a complete review would be unmanageable
in a single paper. Rather selected examples taken from such different areas as
bone-contacting devices, drug eluting stents, and immobilization of novel
biomolecules are presented. The aim is to place the existing and quickly
developing background of analytical and synthetic biomaterial surface science
into the current perspective of this rapidly evolving discipline.
PMID- 17033990
TI - Novel membrane for guided bone regeneration.
AB - Membranes have been clinically used for guided tissue and bone regeneration for
decades, but their use in every day clinical practice is rather limited. We
developed a biodegradable membrane (InionGTR) composed of polylactide,
polyglycolide and trimethylene carbonate aiming to improve the properties of
membrane. Before application the membrane is treated with N-methyl-pyrrolidone
(NMP) to achieve a rubber like consistency, to allow easy handling and
manageability in the clinical setting. After placing the membrane NMP diffuses
out from the polymer phase into the water phase. The loss of NMP in the polymer
stiffens the membrane up and allows space maintenance in the defect area. In
addition the influx and efflux of NMP creates a porous surface on the membrane
leading to an improved integration of tissues into the porous surface layers of
the InionGTR membrane. Therefore, the use of NMP improves the handling in the
clinical setting, and allows tissue integration and space maintenance, both
important for the outcome of the treatment.
PMID- 17033991
TI - 3D bone tissue growth in hollow fibre membrane bioreactor: implications of
various process parameters on tissue nutrition.
AB - New experimental evidence shows that hollow fibre membrane bioreactor (HFMB) may
be applied to grow bulky bone tissues which may then be implanted into patients
to repair skeletal defects. To design effective bone tissue engineering
protocols, it is necessary to determine the quantitative relationships between
the cell environment and tissue behaviour in HFMBs and their relationship with
nutrient supply. It is also necessary to determine under what conditions
nutritional limitations may occur and, hence, may cause cell death. These require
that the appropriate bioreactor conditions for generating neotissues, and the
nutrient transfer behaviour and chemical reaction during cell growth and
extracellular matrix formation are studied thoroughly. In this paper, we aim to
use an existing mathematical framework to analyse the influence of various
relevant parameters on nutrient supply for bone tissue growth in HFMB. We adopt
the well-known Krogh cylinder approximation of the HFMB. The model parameters
(e.g., cell metabolic rates) and operating conditions for the mathematical model
have been obtained from, or correspond to, in-house experiments with the
exception of a few variables which have been taken from the literature. The
framework is then used to study oxygen and glucose transport behaviour in the
HFMB. Influence of a number of important process parameters, e.g., reaction
kinetics, cell density, inlet concentration of nutrients, etc, on the nutrient
distributions have been systematically analysed. The work presented in this paper
provides insights on unfavourable system designs and specifications which may be
avoided to prevent mass transfer limitations for growing bone tissues in HFMB.
PMID- 17033992
TI - Quantitative constitutive behaviour and viscoelastic properties of fresh flexor
tendons.
AB - The objective of this study was to obtain detailed high quality experimental data
under well-controlled test conditions in order to quantify tendon viscoelastic
behaviour and provide an experimental basis for large deformation mathematical
modelling. Eighty-six fresh chicken flexor digitorum profundus (FDP) tendons were
mechanically tested using an Instron 5565 universal testing machine and a Bioplus
bath containing physiological saline solution. At low strain rates ( G SNP (rs2236418) and AD (allele P = 0.038, genotype P = 0.008). An
additional sample of 138 Russian males with AD were genotyped for the GAD2 -243 A
> G. These analyses supported an association of this polymorphism with AD
(combined sample allele P = 0.038, genotype P = 0.0009). We extended these
findings to additional populations: a sample of 538 college students assessed
using the AUDIT and a sample of European-American (EA) AD subjects (n = 235) and
controls (n = 310). Analyses in these populations did not support a role for GAD2
in alcoholism. In summary, the results of an extensive search for an association
of GAD2 with AD suggest that variation in GAD2 is not a major risk factor for AD
in EAs. The functional promoter GAD2 -243 A > G variant may influence risk for AD
in some populations, or its role may be limited to susceptibility to severe AD.
PMID- 17034010
TI - Effect of oxygen inhibition on composite repair strength over time.
AB - The study was aimed at examining whether an oxygen inhibition layer is required
for bonding a repairing to a pre-existing composite, and to determine the time
required for free radicals within a composite substrate to decay to the extent
that the composite repair strength drops significantly. Ten slabs of Gradia
Direct Anterior (GC Corp.) were divided into (1) control group: an interfacial
oxygen inhibition layer was created by applying and light-curing two layers of
bonding resin (D/E Resin, Bisco) to the slabs surface in atmospheric air; (2)
experimental group: the absence of an interfacial oxygen inhibition layer was
obtained by light-curing the second bonding resin layer in a nitrogen atmosphere.
After 1 and 2 h, 1, 14, and 30 days of air storage, a composite repair was
layered over the bonding resin. Microtensile bond strengths were measured and
statistically analyzed. The curing atmosphere was not a significant factor for
bond strength (p = 0.82), and time and curing atmosphere-time interaction were
significant (p < 0.001). The 30 day-strengths were the lowest (p < 0.05). An
oxygen-inhibited layer is not initially required for bonding to resin composite,
and it takes more than 14 days before the bond strength between a pre-existing
and a fresh composite drops.
PMID- 17034011
TI - CO2 laser-induced zonation in dental enamel: a Raman and IR microspectroscopic
study.
AB - The gradient of structural alteration and molecular exchange across CO(2) laser
irradiated areas in dental enamel was analyzed by Raman and attenuated total
reflectance infrared microspectroscopy. The type and the degree of structural
changes in morphologically distinguishable zones within the laser spot vary
depending on the laser-irradiation parameters--power (1 and 3 W), treatment time
(5 and 10 s), and operational mode (super pulse and continuous wave). Using
higher power, irrespective of the operation mode, the enamel tissue ablates and a
crater is formed. The prevalent phase at the bottom of the crater is dehydrated
O(2) (2-)-bearing apatite, that is, the fundamental framework topology is
preserved. Additional nonapatite calcium phosphate phases are located mainly at
the slope of the laser crater. No structural transformation of mineral component
was detected aside the crater rim, only a CO(3)-CO(2) exchange, which decays with
the radial distance. A lower-power laser irradiation slightly roughens the enamel
surface and the structural modification of enamel apatite is considerably weaker
for continuous wave than for super pulse mode. Prolonged low-power laser
treatment results in recrystallization, and thus structural recovering of apatite
might be of clinical relevance for enamel surface treatments.
PMID- 17034012
TI - Evaluation of bone regeneration at critical-sized calvarial defect by DBM/AM
composite.
AB - This study investigated the bone-regenerative potential of a demineralized bone
and acellular matrix (DBM/AM) composite (AlloCraft DBM) in comparison with
autologous bone using an in vivo model. Critical-sized calvarial defects (5 mm)
were created in athymic rats. The defects were grafted with either the DBM/AM
composite or the acellular human dermal matrix (AM), and compared with the
defects filled with autologous bone (positive control) and the empty defect
(negative control). Histological and radiographic assessments were carried out at
4 and 8 weeks after surgery to determine the biological healing, the amount and
type of new bone formation and the percentage of new bone filled in the critical
defects. At 4 weeks, DBM/AM composite group had the highest percentage of the
defect filled with new bone (84%), which was significantly greater than
autologous bone (62%), AM (41%), and untreated control (32%) groups. At 8 weeks,
the DBM/AM continued to have the highest percentage of the defect filled with new
bone (91%). The autologous bone group increased the percentage of bone fill to
83%. The defects either filled with AM or left untreated still had less of the
defect filled with new bone, 57% and 33%, respectively. The total healing of
defects grafted with DBM/AM was comparable with autologous bone group at 8 weeks.
The results demonstrated that the DBM/AM composite promoted new bone formation
more rapidly than autologous bone at calvarial defect in athymic rats. The study
supports that DBM/AM is a potential substitute of autologous bone for bone
repair.
PMID- 17034013
TI - Influence of changes in the composition of an acrylic bone cement on its
polymerization kinetics.
AB - It has been suggested in the literature that a lower polymerization rate of an
acrylic bone cement is favorable for the in vivo longevity of a cemented
arthroplasty. The present work was a study of the influence of three changes in
the composition of an acrylic bone cement (when taken separately) on the cement
polymerization rate at 37 degrees C (assumed to be the temperature in the bone
bed during a cemented arthroplasty) [k']. The changes were the amount of
copolymer as a proportion of the total powder weight (in cements in which there
is a copolymer in the powder), the amount of DMPT as a proportion of the total
volume of the liquid monomer, and the accelerator. k' was calculated using values
of the activation energy and the frequency factor (assuming the polymerization
reaction is Arrhenius in nature) that were computed from measurements made using
the nonisothermal mode of differential scanning calorimetry. Statistical analysis
(one-way ANOVA, with Bonferroni correction, and factorial ANOVA) of the k' values
showed that the change in accelerator had a significant influence on k'. The
importance of this finding, together with results from two relevant literature
reports, is discussed within the context of the use of modified bone cements in
cemented arthroplasties.
PMID- 17034014
TI - Environmental degradation of glass-ionomer cements: a depth-sensing
microindentation study.
AB - This study investigated the effects of various environmental conditions on the
hardness and elastic modulus of restorative glass-ionomer cements (GICs). Two
resin-modified GICs (RMGICs) (Fuji II LC [FL]; Photac-Fil Quick [PQ]) and three
highly viscous GICs (HVGICs) (Fuji IX Fast [FN]; KetacMolar [KM]; KetacMolar
Quick [KQ]) were evaluated in this study. Specimens were fabricated according to
the manufacturers' instructions and stored under a variety of conditions (n = 7):
100% humidity, distilled water, pH 5 demineralization solution, and pH 7
remineralization solution. The hardness and elastic modulus were measured using a
depth-sensing microindentation test after 4 weeks. The results were analyzed
using the independent samples T-test and ANOVA/Scheffe's post hoc test (p <
0.05). HVGICs showed significantly higher hardness and elastic modulus than
RMGICs under all storage conditions. Storage in distilled water significantly
increased the hardness and elastic modulus of FN, but decreased that of PQ. All
HVGICs and RMGICs stored in remineralization solution had hardness values and
elastic moduli comparable to those stored in water. Compared to remineralization
solution, demineralization solution had no significant effects on the modified
GICs with the exception of KQ. The results suggest that the mechanical properties
of glass-ionomer restoratives are material-type and storage condition dependent.
Therefore, the clinical selection of a glass-ionomer material should be based on
the oral environment to which it will be subjected.
PMID- 17034015
TI - Growing tissue-like constructs with Hep3B/HepG2 liver cells on PHBV microspheres
of different sizes.
AB - In this study, an oil-in-water emulsion solvent evaporation technique was used to
fabricate poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV, 8% PHV),
microspheres as scaffold, to guide liver cell growth. Human hepatoma cell lines,
HepG2 and Hep3B, were cultured in vitro on both the microspheres and polymer
films. SEM and optical microscope images showed that multilayer cells were formed
among the microspheres to bridge them together and developed into cell-construct
aggregates after 1 week of culture. MTT results showed that the cell
proliferation on the microspheres was more than two times higher than that on the
films after 12 days of culture. The cells seeded on microspheres secreted albumin
2-4 times more than that on the positive control after 1 week of culture, which
indicated that this hepatic function was greatly improved by the aggregation of
cells on microspheres. Although HepG2 failed to express P-450 activity, this
hepatic function was preserved when Hep3B cultured on microspheres. All the
results indicated that PHBV microspheres are appropriate scaffolds for liver
tissue engineering.
PMID- 17034016
TI - Safety evaluation of large external fixation clamps and frames in a magnetic
resonance environment.
AB - Large orthopedic external fixation clamps and related components were evaluated
for force, torque, and heating response when subjected to the strong
electromagnetic fields of magnetic-resonance (MR) imaging devices. Forces induced
by a 3-Tesla (T) MR scanner were compiled for newly designed nonmagnetic clamps
and older clamps that contained ferromagnetic components. Heating trials were
performed in a 1.5 and in a 3 T MR scanner with two assembled external fixation
frames. Forces of the newly designed clamps were more than a factor 2 lower as
the gravitational force on the device whereas, magnetic forces on the older
devices showed over 10 times the force induced by earth acceleration of gravity.
No torque effects could be found for the newly designed clamps. Temperature
measurements at the tips of Schanz screws in the 1.5 T MR scanner showed a rise
of 0.7 degrees C for a pelvic frame and of 2.1 degrees C for a diamond knee
bridge frame when normalized to a specific absorption rate (SAR) of 2 W/kg. The
normalized temperature increases in the 3 T MR scanner were 0.9 degrees C for the
pelvic frame and 1.1 degrees C for the knee bridge frame. Large external fixation
frames assembled with the newly designed clamps (390 Series Clamps), carbon fiber
reinforced rods, and implant quality 316L stainless steel Schanz screws met
prevailing force and torque limits when tested in a 3-T field, and demonstrated
temperature increase that met IEC-60601 guidelines for extremities. The influence
of frame-induced eddy currents on the risk of peripheral nerve stimulation was
not investigated.
PMID- 17034017
TI - Adolescent girls and criminal activity: role of MAOA-LPR genotype and
psychosocial factors.
AB - Recent findings among boys show that interactions between a polymorphism in the
monoamine oxidase A gene promoter region (MAOA-LPR) and psychosocial factors
predict criminal activity. The objective of this study was to investigate whether
this finding could be extended to adolescent girls. One hundred nineteen female
adolescents were recruited among respondents to a cross-sectional study of the
total population of 16- and 19-year old girls. These girls constituted a randomly
selected sub-sample from groups representing different degrees of risk behavior.
The subjects filled in a questionnaire and were interviewed and genotyped with
regard to MAOA-LPR. The results indicate that the long, (4-repeat) allele confer
an increased risk for criminal behavior in the presence of psychosocial risk.
Among girls without social risk, MAOA-LPR genotype was of no importance for
criminal behavior. The present results suggest that previous observations on
adolescent males, which demonstrate that the short MAOA-LPR genotype and
psychosocial adversity interact to predict criminal activity, may not be
applicable to females.
PMID- 17034018
TI - Schizotypal dimensions: an intermediate phenotype associated with the COMT high
activity allele.
AB - BACKGROUND: Although catechol-O-methyltransferase (COMT) has long been suggested
to be implicated in the pathogenesis of schizophrenia, association studies have
generated discrepant results concerning the involvement of the COMT gene in
schizophrenia. As several studies have suggested that schizotypal traits might be
genetically related to schizophrenia, increased statistical power to detect gene
effects could be obtained by using dimensional personality traits in unaffected
relatives. METHODS: We tested the hypothesis that the functional Val158Met COMT
polymorphism might contribute to the variance of self-reported schizotypal scores
in a sample of 106 unaffected subjects, composed of controls (N = 57), first
degree relatives of schizophrenic (N = 27) and of bipolar (N = 22) probands. We
also looked for specific associations between COMT polymorphisms and the three
dimensions of schizotypy (positive, negative, disorganized) assessed by the
Schizotypal Personality Questionnaire (SPQ). RESULTS: We found that self-reported
SPQ scores are related to COMT genotype (P = 0.01), with individuals homozygous
for the high activity allele having the highest scores. This association is
primarily due to specific associations with the positive (P = 0.001) and negative
(P = 0.04) dimensions. CONCLUSIONS: Our data support the hypothesis that the
functional COMT polymorphism could be involved in different psychotic dimensions.
This confirms that studying specific schizotypal dimensions can help to identify
the genes involved in the pathogenesis of psychosis.
PMID- 17034019
TI - The Palau Early Psychosis Study: distribution of cases by level of genetic risk.
AB - The Palau Early Psychosis Study (PEPS) was designed to examine the pathogenesis
of early psychosis in a high-risk population isolate. This paper describes the
characteristics of our community-based, non-help seeking sample of 404 Palauan
adolescents and quantifies the presence of early psychosis by level of genetic
risk. The sample included 53 offspring of a schizophrenic parent designated as
"Genetically Highest Risk" (GHR+) and 68 nieces/nephews of sib-pairs/trios,
designated as "Genetically High Risk" (GHR). The remaining subjects were
recruited through a high school survey that identified 62 "Genetically Moderate
Risk" (GMR) adolescents with an affected second or third degree relative and 221
"Genetically Low Risk" (GLR) subjects with no close affected relatives. The GLR
adolescents included 117 symptomatic or "Clinically High Risk" (CHR) adolescents
and 104 asymptomatic normal controls. Based on a modified K-SADS-PL assessment,
we identified 221 adolescents with early psychosis, 62 or 28% of whom had already
transitioned to a psychotic disorder. Together, the two highest risk groups
contributed 31% of the adolescent-onset psychosis cases and 27% of the
prodromals. More than half of the early psychosis cases (53%) were GLR
adolescents. The mean age of onset for DSM-IV psychosis was 12.9 years, and males
transitioned at an earlier age than females. Our results indicate that Palauan
adolescents, even GLR adolescents with no close affected relatives, have elevated
rates of early psychosis. These young subjects can contribute valuable
information about the familial transmission of schizophrenia, the developmental
course of the illness, and rates of transition to frank psychosis.
PMID- 17034020
TI - No association between ADRA2A polymorphisms and schizophrenia.
AB - There is evidence to suggest that the alpha(2A)-adrenergic receptor may be
involved in schizophrenia. With attention directed at the upstream regulatory
region of the gene which codes for this receptor (ADRA2A), we proposed that
single nucleotide polymorphisms (SNPs) within this region influences
susceptibility to schizophrenia by altering the expression of this receptor. We
opted to test for an influence on susceptibility by association study using 112
schizophrenic/schizoaffective disorder patients and 159 controls. The region of
interest was screened for SNPs using a combination of bioinformatic searches and
sequencing. A total of nine SNPs were discovered, of which four (-5972-G/A, -2211
A/T, -1291-C/G and -261-G/A) were genotyped in the entire clinical sample. No
associations were evident, suggesting no influence for these SNPs in
susceptibility to schizophrenia.
PMID- 17034021
TI - Schizophrenic-like neurocognitive deficits in children and adolescents with 22q11
deletion syndrome.
AB - 22q11.2 Deletion Syndrome (22q11DS) is the most common genetic microdeletion
syndrome affecting humans. The syndrome is associated with general cognitive
impairments and specific deficits in visual-spatial ability, non-verbal
reasoning, and planning skills. 22q11DS is also associated with behavioral and
psychiatric abnormalities, including a markedly elevated risk for schizophrenia.
Research findings indicate that people with schizophrenia, as well as those
identified as schizoptypic, show specific cognitive deficits in the areas of
sustained attention, executive functioning, and verbal working memory. The
present study examined such schizophrenic-like cognitive deficits in children and
adolescents with 22q11DS (n = 26) and controls (n = 25) using a cross-sectional
design. As hypothesized, 22q11DS participants exhibited deficits in intelligence,
achievement, sustained attention, executive functioning, and verbal working
memory compared to controls. Furthermore, deficits in attention and executive
functioning were more pronounced in the 22q11DS sample relative to general
cognitive impairment. These findings suggest that the same pattern of
neuropsychological impairment seen in patients with schizophrenia is present in
non-psychotic children identified as at-risk for the development of schizophrenia
based on a known genetic risk marker.
PMID- 17034022
TI - Adjudicating neurocognitive endophenotypes for schizophrenia.
AB - Although genetic influences on schizophrenia are well established, localization
of the genes responsible for this illness has proven extremely difficult. Given
evidence that genes predisposing to schizophrenia may be transmitted without
expression of the clinical phenotype, efforts have focused on developing
endophenotypes. While several neuropsychological measures have been proposed to
be endophenotypes, few studies have systematically assessed batteries of
neurocognitive tests to determine which tests are most sensitive to liability for
the illness. Two hundred sixty-nine Latino individuals were administered a
standard neuropsychological battery. Two hundred fourteen of these were members
of families with at least two siblings diagnosed with schizophrenia or
schizoaffective disorder. The remaining were community controls without history
of major psychiatric illness. Neurocognitive measures found to be heritable were
entered into analyses designed to determine which tests covary with the degree of
genetic relationship to affected individuals. Although five measures were found
to uniquely model genetic liability for schizophrenia, digit symbol coding was
the most sensitive. To assess the specificity of these endophenotypes,
performance on these measures were compared to family members with bipolar and
unipolar affective disorders. These markers clearly distinguished between
individuals with psychotic illnesses and those with major depression. As measures
contributed uniquely to discriminate individuals at varying risk for
schizophrenia, our findings imply multiple independently inherited elements to
the liability for the illness. We present a practical model for adjudicating
endophenotypes and determining which measures are best suited for use in linkage
analyses.
PMID- 17034023
TI - PTPN22 620W allele is not associated with aplastic anemia.
AB - The 1858C/T variant in PTPN22 imparts a gain of function mutation dysregulating T
cell stimulation and is associated with an array of autoimmune diseases. Using a
case-control design, we compared the frequency of this polymorphism in 91
patients with acquired aplastic anemia to 132 ethnically matched controls.
Representation of the PTPN22 variant was not significantly different between the
two populations, suggesting that this gene polymorphism does not contribute to
the etiology of aplastic anemia. Aplastic anemia thus joins a list of autoimmune
diseases that commonly lack a major humoral disease component and do not
associate with the PTPN22 variant.
PMID- 17034024
TI - Profound thrombocytopenia related to G-CSF.
AB - Severe thrombocytopenia in association with G-CSF therapy is extremely rare. Here
we report a case of profound thrombocytopenia in a 57-year-old male with
refractory cardiac ischemia, who received G-CSF during an angiogenesis trial.
After 5 days of G-CSF therapy (10 microg/kg/day) the platelet count fell
progressively to a nadir of 5x10(9)/L. The patient received steroid,
immunoglobulin and platelet support and recovered without sequelae. Subsequent
investigations suggested an underlying immune-mediated thrombocytopenia, which we
hypothesize was exacerbated by G-CSF therapy.
PMID- 17034025
TI - Post-appendectomy thrombotic thrombocytopenic purpura: a case report and review
of the literature.
AB - Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by
microangiopathic hemolytic anemia and thrombocytopenia with varying degrees of
renal dysfunction, neurologic signs and symptoms, and fever. Evidence has
supported that a large proportion of cases of acquired TTP are due to the
accumulation of ultralarge von Willebrand factor (vWF) multimers due to an
acquired deficiency in the vWF cleaving protease, ADAMTS-13. TTP is rare in the
post-surgical setting but is best described after cardiothoracic and vascular
surgeries. We present a case of postoperative TTP first presenting with
microangiopathic hemolytic anemia and thrombocytopenia 9 days after emergent
appendectomy for a ruptured appendix. ADAMTS-13 and factor H levels returned
normal and an ADAMTS-13 inhibitor was not identified. To our knowledge, this is
the first case report of postoperative TTP after an appendectomy and the first
report with correlative ADAMTS-13 data. Plasma exchange with fresh frozen plasma
followed by cryopoor plasma, along with steroids resulted in eventual remission
of TTP in our patient. Early postoperative diagnosis and aggressive management
with consideration of initiation of plasma exchange is imperative to decrease the
morbidity and morality associated with TTP.
PMID- 17034026
TI - Retrochorionic hematoma in congenital afibrinogenemia: resolution with fibrinogen
concentrate infusions.
AB - Without treatment, pregnancies in patients with congenital afibrinogenemia
terminate in miscarriage at 5-6 weeks of gestation. Animal model studies have
suggested that implantation site bleeding contributes to miscarriage in
afibrinogenemia; however, retrochorionic hematoma in human congenital
afibrinogenemia has not been previously observed. A patient with congenital
afibrinogenemia receiving fibrinogen prophylaxis developed a retrochorionic
hematoma in the first trimester. With continuous intensified fibrinogen
concentrate replacement the hematoma resolved over 6 weeks, and the patient
delivered a healthy infant. Median fibrinogen levels in the first trimester were
48 mg/dL and in second and third trimester 44 mg/dL. Median fibrinogen levels
under 60 mg/dL may be adequate to maintain pregnancy in patients with congenital
afibrinogenemia, although it is possible that higher levels might reduce the risk
of hemorrhagic events.
PMID- 17034027
TI - Estimated glomerular filtration rate in sickle cell anemia is associated with
polymorphisms of bone morphogenetic protein receptor 1B.
AB - Renal disease is common in sickle cell anemia. In this exploratory work, we used
data from a longitudinal study of the natural history of sickle cell disease to
examine the hypothesis that polymorphisms (SNPs) in selected candidate genes are
associated with glomerular filtration rate (GFR). DNA samples and clinical and
laboratory data were available for 1,140 patients with sickle cell anemia. GFR
was estimated using the Cockcroft-Gault and Schwartz formulas for adults and
children, respectively. We examined approximately 175 haplotype tagging (ht) SNPs
in about 70 genes of the TGFbeta/BMP pathway for their association with GFR using
linear regression. Four SNPs in BMPR1B, a bone morphogenetic protein (BMP)
receptor gene, yielded statistically significant associations (P values ranging
from 0.015 to 0.046). Three haplotypes in this gene were also associated with
GFR. The TGF-beta/BMP pathway has been associated with the development of
diabetic nephropathy, which has some features in common with sickle cell
nephropathy. Our results suggest that, as with other subphenotypes of sickle cell
disease, renal function may be genetically modulated.
PMID- 17034028
TI - Characterization of a novel deletion causing (deltabeta)0-thalassemia in a Thai
family.
AB - A novel deletion of the human beta-globin gene cluster associated with the
increased level of fetal hemoglobin (Hb F) in adult life has been demonstrated in
a Thai family. A Thai girl who was mistakenly diagnosed as beta-thalassemia/HbE
is found to be the compound heterozygote of this mutation and Hb E. The
heterozygous father had mild hypochromic and microcytic red blood cells and a
high level of Hb F (23.2%). Polymorphic restriction sites in the beta-globin gene
cluster identified the homozygous alleles, which localized the deletion region
between the psibeta-globin and the 3' beta-globin genes. DNA polymerase that can
amplify a long DNA template was employed to examine DNA fragment encompassing
this deletion. A 11.3 kilobases (kb) of DNA deletion, beginning approximately 3.1
kb 5' to the delta-globin gene and end in the intron 2 of the beta-globin gene
was detected. DNA analysis revealed that this is a case of (deltabeta)(0)
thalassemia with a novel mutation, which can lead to a mild form of beta
thalassemia upon interaction with Hb E.
PMID- 17034029
TI - Congenital amegakaryocytic thrombocytopenia--report of a new c-mpl gene missense
mutation.
AB - A 44-month old girl with congenital amegakaryocytic thrombocytopenia, already
with pancytopenia, underwent an unrelated allogeneic cord blood transplantation
with recovery of normal blood cell counts. The patient was a compound
heterozygote for two c-mpl missense mutations inherited from both parents, one of
them, a G578A exon 4 mutation leading to a cysteine to tyrosine replacement of
codon 193, previously unreported.
PMID- 17034030
TI - Management of cancer-associated thrombotic microangiopathy: what is the right
approach?
AB - A 49-year-old Caucasian woman presented with features suggestive of thrombotic
microangiopathy (TMA). She did not respond to treatment with repeated plasma
exchange and corticosteroids. A bone marrow biopsy revealed presence of
metastatic carcinoma. A limited autopsy revealed presence of breast cancer with
rib metastases. Though severe deficiency of von Willebrand factor-cleaving
protease was initially proposed as a key pathogenetic factor for thrombotic
thrombocytopenic purpura, subsequent studies involving patients with cancer
associated TMA did not find as severe a deficiency of von Willebrand factor
cleaving protease as is seen in idiopathic cases of thrombotic thrombocytopenic
purpura. Here we address one approach of management of these patients with cancer
associated TMA.
PMID- 17034031
TI - Microrough titanium surface affects biologic response in MG63 osteoblast-like
cells.
AB - The purpose of this study was to define the surface properties of prepared
titanium (Ti) disks, which served as a model system, and to contrast the biologic
response of MG63 cells exposed to Ti disks with different levels of surface
roughness. The surface properties interact with each other, resulting in a change
of other surface qualities in addition to roughness due to the surface roughening
procedure. The machined Ti disks were roughened by sandblasting and electric glow
discharging. The surface properties of the Ti specimens were inspected through a
comprehensive surface analysis. MG63 cell behaviors were compared along with cell
number, alkaline phosphatase (ALP) activity, Runx2 gene expression, and type I
collagen production. Statistics were evaluated, using analysis of variance
(ANOVA). The sandblasted Ti disks demonstrated well-controlled surface roughness
features and meaningful average roughness ranges, including the surface roughness
of the "modern" microrough implant, used clinically. With increasing Ti surface
roughness, the cell number decreased, while the ALP activity, type I collagen
production, and Runx2 gene expression increased significantly. The rougher the Ti
surface was, the sooner the Runx2 gene was expressed. Based on these results, we
suggest that the microrough Ti surfaces of the 1-3 mum range may contribute
effectively to osteogenic differentiation and proliferation in MG63 cells.
PMID- 17034032
TI - Timing of radiation in children with medulloblastoma/PNET.
AB - BACKGROUND: To evaluate the importance of timing of radiation therapy in children
with PNET/medulloblastoma, treated at the Brazilian National Cancer Institute
(INCA). PROCEDURE: The records of 101 children with confirmed diagnosis of
medulloblastoma were retrospectively reviewed. Patients had a median follow-up of
48 months (0.5-241 months). The age varied from 0.8 to 17.5 years (median: 7.6
years) and 21.7% were 3 years old or younger. RESULTS: According to the data
collected from patients that received treatment for medulloblastoma from 1983 to
2001, the overall survival (OS) rate was 53% and the Disease Free Survival (DFS)
rate was 40%. Multivariate analysis showed that under age 3 years, presence of
neoplasic cells in the cerebrospinal fluid (CSF) at presentation or subtotal
tumor resection resulted in a worse OS. The patients that received a biological
effective dose (BED) greater than 44 Gy10 had better prognosis. Two-thirds of the
patients had complete response after the initial treatment. Among them, 50% (34
patients) recurred, and of those 34 patients, 42% of them (14 patients) had
recurrence in the posterior fossa. CONCLUSION: Surgery with total resection of
the tumor and absence of neoplasic cells in the CSF are effective predictors of
better OS. Radiotherapy was more effective when a BED was greater than 44 Gy10.
PMID- 17034033
TI - Expression and activation of alpha v beta 3 integrins by SDF-1/CXC12 increases
the aggressiveness of prostate cancer cells.
AB - BACKGROUND: Stromal cell-derived factor-1 (SDF-1 or CXCL12) and CXCR4 are key
elements in the metastasis of prostate cancer cells to bone--but the mechanisms
as to how it localizes to the marrow remains unclear. METHODS: Prostate cancer
cell lines were stimulated with SDF-1 and evaluated for alterations in the
expression of adhesion molecules using microarrays, FACs, and Western blotting to
identify alpha(v)beta(3) receptors. Cell-cell adhesion and invasion assays were
used to verify that activation of the receptor is responsive to SDF-1. RESULTS:
We demonstrate that SDF-1 transiently regulates the number and affinity of
alpha(v)beta(3) receptors by prostate cancer cells to enhance their metastatic
behavior by increasing adhesiveness and invasiveness. SDF-1 transiently increased
the expression of beta(3) receptor subunit and increased its phosphorylation in
metastatic but not nonmetastatic cells. CONCLUSIONS: The transition from a
locally invasive phenotype to a metastatic phenotype may be primed by the
elevated expression of alpha(v)beta(3) receptors. Activation and increased
expression of alpha(v)beta(3) within SDF-1-rich organs may participate in
metastatic localization.
PMID- 17034034
TI - Imaging brain activity during natural vision using CASL perfusion fMRI.
AB - Functional MRI (fMRI) has begun to be used to explore human brain activity during
ecological and natural conditions. Arterial spin labeling (ASL) perfusion fMRI
provides an appealing approach for imaging sustained brain activity during
natural conditions because of its long-term temporal stability and ability to
noninvasively quantify absolute cerebral blood flow (CBF). The present study used
ASL perfusion fMRI to measure brain activation patterns associated with natural
vision by concurrently recording CBF and blood oxygen level-dependent (BOLD)
contrasts while subjects were freely viewing a cartoon movie. Reliable
quantitative whole-brain CBF values ( approximately 60 mL/100g/min) as well as
regional CBF values (45 approximately 80 mL/100g/min) were measured during movie
viewing and resting states. The perfusion contrast revealed CBF increases in
multiple visual pathway areas and frontal areas, and CBF decreases in
ventromedial frontal cortex and superior temporal cortex during movie viewing
compared to resting states. Concurrent BOLD contrast revealed similar but weaker
activation and deactivation patterns. Regression analyses of both CBF data and
BOLD data showed significant associations between activation in the middle
temporal (MT) region and subjects' perception of motion. Region of interest
analysis based on a priori literature-defined MT demonstrated significant
monotonic stepwise associations between the intensity of motion perception and
the CBF and BOLD signal changes. These results demonstrate the feasibility of
using ASL perfusion fMRI for imaging both sustained and dynamic effects in neural
activation during natural and ecologically valid situations, and support the
notion of maintained functional segregation and specialization during natural
vision.
PMID- 17034035
TI - Thermodynamic effects of proline introduction on protein stability.
AB - The amino acid Pro is more rigid than other naturally occurring amino acids and,
in proteins, lacks an amide hydrogen. To understand the structural and
thermodynamic effects of Pro substitutions, it was introduced at 13 different
positions in four different proteins, leucine-isoleucine-valine binding protein,
maltose binding protein, ribose binding protein, and thioredoxin. Three of the
maltose binding protein mutants were characterized by X-ray crystallography to
confirm that no structural changes had occurred upon mutation. In the remaining
cases, fluorescence and CD spectroscopy were used to show the absence of
structural change. Stabilities of wild type and mutant proteins were
characterized by chemical denaturation at neutral pH and by differential scanning
calorimetry as a function of pH. The mutants did not show enhanced stability with
respect to chemical denaturation at room temperature. However, 6 of the 13 single
mutants showed a small but significant increase in the free energy of thermal
unfolding in the range of 0.3-2.4 kcal/mol, 2 mutants showed no change, and 5
were destabilized. In five of the six cases, the stabilization was because of
reduced entropy of unfolding. However, the magnitude of the reduction in entropy
of unfolding was typically several fold larger than the theoretical estimate of
4 cal K(-1) mol(-1) derived from the relative areas in the Ramachandran map
accessible to Pro and Ala residues, respectively. Two double mutants were
constructed. In both cases, the effects of the single mutations on the free
energy of thermal unfolding were nonadditive.
PMID- 17034036
TI - Complexity of free energy landscapes of peptides revealed by nonlinear principal
component analysis.
AB - Employing the recently developed hierarchical nonlinear principal component
analysis (NLPCA) method of Saegusa et al. (Neurocomputing 2004;61:57-70 and IEICE
Trans Inf Syst 2005;E88-D:2242-2248), the complexities of the free energy
landscapes of several peptides, including triglycine, hexaalanine, and the C
terminal beta-hairpin of protein G, were studied. First, the performance of this
NLPCA method was compared with the standard linear principal component analysis
(PCA). In particular, we compared two methods according to (1) the ability of the
dimensionality reduction and (2) the efficient representation of peptide
conformations in low-dimensional spaces spanned by the first few principal
components. The study revealed that NLPCA reduces the dimensionality of the
considered systems much better, than did PCA. For example, in order to get the
similar error, which is due to representation of the original data of beta
hairpin in low dimensional space, one needs 4 and 21 principal components of
NLPCA and PCA, respectively. Second, by representing the free energy landscapes
of the considered systems as a function of the first two principal components
obtained from PCA, we obtained the relatively well-structured free energy
landscapes. In contrast, the free energy landscapes of NLPCA are much more
complicated, exhibiting many states which are hidden in the PCA maps, especially
in the unfolded regions. Furthermore, the study also showed that many states in
the PCA maps are mixed up by several peptide conformations, while those of the
NLPCA maps are more pure. This finding suggests that the NLPCA should be used to
capture the essential features of the systems.
PMID- 17034037
TI - Stress urinary incontinence as the presenting symptom of primary male urethral
diverticulum-A case report and literature review.
AB - Primary male urethral diverticulum is quite uncommon. It is even more unusual for
urinary incontinence to be a presenting symptom of primary male urethral
diverticulum. Herein, we report on a 32-year-old male presenting with urine
leakage on coughing or abdominal strain beginning from his early twenties. A
congenital type bulbar urethral diverticulum is diagnosed by voiding
cystourethrography and cystourethroscopy. Endoscopic unroofing of the
diverticulum freed the patient from stress urinary incontinence after the
surgery.
PMID- 17034038
TI - Dynamics and assembly of the cytolethal distending toxin.
AB - The cytolethal distending toxin (CDT) is a widespread bacterial toxin that
consists of an active subunit CdtB with nuclease activity and two ricin-like
lectin domains, CdtA and CdtC, that are involved in the delivery of CdtB into the
host cell. The three subunits form a tripartite complex that is required to
achieve the fully active holotoxin. In the present study we investigate the
assembly and dynamic properties of the CDT holotoxin using molecular dynamics
simulations and binding free energy calculations. The results have revealed that
CdtB likely adopts a different conformation in the unbound state with a closed
DNA binding site. The two characterized structural elements of the aromatic patch
and groove on the CdtA and CdtC protein surfaces exhibit high mobility, and free
energy calculations show that the heterodimeric complex CdtA-CdtC, as well as the
CdtA-CdtB and CdtB-CdtC sub-complexes are less energetically stable as compared
to the binding in the tripartite complex. Analysis of the dynamical cross
correlation map reveals information on the correlated motions and long-range
interplay among the CDT subunits associated with complex formation. Finally, the
estimated binding free energies of subunit interactions are presented, together
with the free energy decomposition to determine the contributions of residues for
both binding partners, providing insight into the protein-protein interactions in
the CDT holotoxin.
PMID- 17034039
TI - Needle electromyography of the rectus abdominis in patients with amyotrophic
lateral sclerosis.
AB - We examined the role of needle electromyography (EMG) of the rectus abdominis
(RA) in assessing thoracic involvement in amyotrophic lateral sclerosis (ALS).
Needle EMG of the RA was performed in 67 patients with sporadic ALS and 110
healthy controls. The presence of abnormal spontaneous activity, configuration of
motor unit action potentials (MUAPs), and recruitment pattern of motor unit
potentials were examined. In ALS patients, MUAPs in the RA were of prolonged
duration, large amplitude, and showed increased prevalence of polyphasic
waveforms compared to controls. Significant differences in MUAP parameters,
presence of abnormal spontaneous potentials, and interference patterns were noted
between ALS patients and controls. Additionally, we found that active denervation
was more frequent in the RA of ALS patients with dyspnea than those without
dyspnea. Thus, conventional needle EMG of the RA is a valuable
electrophysiological method to assess clinical and subclinical involvement of
thoracic lower motor neurons in patients with suspected ALS.
PMID- 17034040
TI - Electrical stimulation based on chronaxie reduces atrogin-1 and myoD gene
expressions in denervated rat muscle.
AB - Denervation induces muscle fiber atrophy and changes in the gene expression rates
of skeletal muscle. Electrical stimulation (ES) is a procedure generally used to
treat denervated muscles in humans. This study evaluated the effect of ES based
on chronaxie and rheobase on the expression of the myoD and atrogin-1 genes in
denervated tibialis anterior (TA) muscle of Wistar rats. Five groups were
examined: (1) denervated (D); (2) D+ES; (3) sham denervation; (4) normal (N); and
(5) N+ES. Twenty muscle contractions were stimulated every 48 h using surface
electrodes. After 28 days, ES significantly decreased the expression of myoD and
atrogin-1 in D+ES compared to the D group. However, ES did not prevent muscle
fiber atrophy after denervation. Thus, ES based on chronaxie values and applied
to denervated muscles using surface electrodes, as normally used in human
rehabilitation, was able to reduce the myoD and atrogin-1 gene expressions, which
are related to muscular growth and atrophy, respectively. The results of this
study provide new information for the treatment of denervated skeletal muscle
using surface ES.
PMID- 17034041
TI - Ligand-supported homology modeling of the human angiotensin II type 1 (AT(1))
receptor: insights into the molecular determinants of telmisartan binding.
AB - Angiotensin II type 1 (AT(1)) receptor belongs to the super-family of G-protein
coupled receptors, and antagonists of the AT(1) receptor are effectively used in
the treatment of hypertension. To understand the molecular interactions of these
antagonists, such as losartan and telmisartan, with the AT(1) receptor, a
homology model of the human AT(1) (hAT(1)) receptor with all connecting loops was
constructed from the 2.6 A resolution crystal structure (PDB i.d., 1L9H) of
bovine rhodopsin. The initial model generated by MODELLER was subjected to a
stepwise ligand-supported model refinement. This protocol involved initial
docking of non-peptide AT(1) antagonists in the putative binding site, followed
by several rounds of iterative energy minimizations and molecular dynamics
simulations. The final model was validated based on its correlation with several
structure-activity relationships and site-directed mutagenesis data. The final
model was also found to be in agreement with a previously reported AT(1)
antagonist pharmacophore model. Docking studies were performed for a series of
non-peptide AT(1) receptor antagonists in the active site of the final hAT(1)
receptor model. The docking was able to identify key molecular interactions for
all the AT(1) antagonists studied. Reasonable correlation was observed between
the interaction energy values and the corresponding binding affinities of these
ligands, providing further validation for the model. In addition, an extensive
unrestrained molecular dynamics simulation showed that the docking-derived bound
pose of telmisartan is energetically stable. Knowledge gained from the present
studies can be used in structure-based drug design for developing novel ligands
for the AT(1) receptor.
PMID- 17034042
TI - Osteoactivin acts as downstream mediator of BMP-2 effects on osteoblast function.
AB - Our laboratory previously showed that osteoactivin (OA) is a novel, osteoblast
related glycoprotein that plays a role in osteoblast differentiation and
function. The purpose of this study was to examine the regulation of OA
expression by BMP-2 and the role OA plays as a downstream mediator of BMP-2
effects in osteoblast function. Using primary osteoblast cultures, we tested
different doses of BMP-2 on the regulation of OA expression during osteoblast
development. To test whether Smad-1 signaling is responsible for BMP-2 regulation
of OA expression, osteoblast cultures were transfected with Smad1 siRNA, treated
with 50 ng/ml of BMP-2 and analyzed by Western blot. BMP-2 treatment increased OA
mRNA and protein expression in a dose-dependent manner and this upregulation was
blocked in Smad1 siRNA transfected cultures. We next examined whether the role of
OA as a downstream mediator of BMP-2 effects on osteoblast differentiation and
matrix mineralization. Osteoblast cultures were transfected with OA antisense
oligonucleotides and treated with 50 ng/ml of BMP-2. Cultures transfected with OA
antisense oligonucleotides and treated with BMP-2 showed a reduction of OA
expression associated with a significant reduction in early and late
differentiation markers induced by BMP-2. Therefore, OA acts, at least in part,
as a downstream mediator of BMP-2 effects on osteoblast differentiation and
matrix mineralization. Our findings suggest that BMP-2 regulates OA expression
through the Smad1 signaling pathway. Our data also emphasize that OA protein acts
as a downstream mediator of BMP-2 effects on osteoblast differentiation and
function.
PMID- 17034043
TI - Identification of OORP-T, a novel oocyte-specific gene encoding a protein with a
conserved oxysterol binding protein domain in rainbow trout.
AB - Genes specifically expressed in oocytes are important for the development of
oocytes and early embryos. By analyzing expressed sequence tags (ESTs) from a
rainbow trout oocyte cDNA library, we identified a novel EST sequence that does
not show homology to any sequences in the GenBank. Analysis of tissue
distribution by RT-PCR revealed that this gene was only expressed in unfertilized
oocytes. Sequencing of the EST clone identified a cDNA of 3,163 bp. Northern blot
analysis showed the novel gene has a single transcript of 3.4 kb. Additional 5'
sequence was obtained by 5' RACE, extending the novel cDNA to 3,333 bp. Analysis
of the full-length cDNA identified an open reading frame (ORF) encoding a protein
of 564 amino acids. The novel protein contains a conserved oxysterol binding
protein (OSBP) domain at the C terminus that is characteristic of OSBP-related
proteins (ORPs) implicated in lipid metabolism. Therefore, we named the novel
gene as Oocyte-specific Oxysterol binding protein Related-Protein of Trout (OORP
T). In situ hybridization showed that the OORP-T mRNA appears to be confined to
the cytoplasm of vitellogenic oocytes. Transcription of OORP-T appears to start
during pre-vitellogenesis and increases steadily, reaching its peak in the late
vitellogenic stage. OORP-T transcript is abundantly present in unfertilized eggs
but the level drops significantly in day 2 embryos and continues to decline in
day 7 embryos after which it remains low. We propose that OORP-T may play an
important role in the utilization of yolk-derived lipid products during oocyte
development and early stages of embryonic development in rainbow trout.
PMID- 17034044
TI - Interspecies nuclear transfer of Tibetan antelope using caprine oocyte as
recipient.
AB - Interspecies nuclear transfer is an invalulable tool for studying nucleus
cytoplasm interactions; and at the same time, it provides a possible alternative
to clone endangered animals whose oocytes are difficult to obtain. In the present
study, we investigated the possibility of cloning Tibetan antelope embryos using
abattoir-derived caprine oocytes as recipients. Effects of culture conditions,
enucleation timing, and donor cell passages on the in vitro development of
Tibetan antelope-goat cloned embryos were studied. Maternal to zygotic transition
timing of interspecies Tibetan antelope embryos was also investigated using two
types of cloned embryos, Tibetan antelope-rabbit and Tibetan antelope-goat
embryos. Our results indicate that: (1) goat oocyte is able to reprogram somatic
cells of different genus and supports development to blastocyst in vitro. (2)
Coculture system supported the development of Tibetan antelope-goat embryos to
blastocyst rate stage (4.0%), while CR1aa alone did not. (3) When MII phase
enucleated caprine cytoplast and TII phase enucleated caprine cytoplast were used
as recipients, the fusion rate and blastocyst rate of hybrid embryos were not
statistically different (73.9% vs. 67.4%; 4.0% vs. 1.1%). (4) When donor cells at
3-8 passages were used, 2.9% hybrid embryos developed to blastocysts, while none
developed to blastocysts when cells at 10-17 passages were used. (5) There may be
a morula-to-blastocyst block for Tibetan antelope-goat, while there may be an 8-
to 16-cell block for Tibetan antelope-rabbit embryos.
PMID- 17034045
TI - Improved beta-protein structure prediction by multilevel optimization of nonlocal
strand pairings and local backbone conformation.
AB - Proteins with complex, nonlocal beta-sheets are challenging for de novo structure
prediction, due in part to the difficulty of efficiently sampling long-range
strand pairings. We present a new, multilevel approach to beta-sheet structure
prediction that circumvents this difficulty by reformulating structure generation
in terms of a folding tree. Nonlocal connections in this tree allow us to
explicitly sample alternative beta-strand pairings while simultaneously exploring
local conformational space using backbone torsion-space moves. An iterative,
energy-biased resampling strategy is used to explore the space of beta-strand
pairings; we expect that such a strategy will be generally useful for searching
large conformational spaces with a high degree of combinatorial complexity.
PMID- 17034046
TI - Serial nuclear transfer improves the developmental potential of mouse embryos
cloned from oocytes matured in a protein-free medium.
AB - Germinal vesicle (GV) oocytes matured in vitro are an alternative source for
cytoplasmic recipients of nuclear transfer (NT). However, the developmental
potential of oocytes matured in vitro is limited. In this study, we developed a
protein-free maturation medium for mouse GV oocytes. Following parthenogenetic
activation, the oocytes matured in the protein-free medium develop to blastocyst
stage with a high efficiency, even up to the rate obtained from in vivo MII
oocytes (90.6% vs. 92.8%). Using the oocytes matured in the protein-free medium
as the recipient, NT embryos develop to the blastocyst stage (17.6%). To further
improve the developmental potential of NT embryos, we performed serial NT and
compared the effect of three different activated cytoplasm samples derived from
in vitro matured oocytes as the second recipient, that is, the effect of in vitro
fertilized (IVF) zygote, the preactivated cytoplast and the IVF cytoplast, on the
development of NT embryos. We found that when the pronucleus of NT zygote was
transferred into the cytoplasm of the IVF zygote, the blastocyst formation
increased to 39.4%. This is the first report to demonstrate the IVF zygote from
oocytes matured in protein-free medium can be used successfully as the recipient
for serial NT to enhance the developmental potential of mouse NT embryos from
oocytes matured in the protein-free medium.
PMID- 17034047
TI - Digital image analysis of the flagellar beat of activated and hyperactivated
suncus spermatozoa.
AB - The flagellar beat of hyperactivated Suncus spermatozoa was analyzed by digital
imaging and was compared to that of the nonhyperactivated (activated) spermatozoa
in order to examine the function of the accessory fibers during the flagellar
beat and the sliding filament mechanism inducing the motility of the
hyperactivated spermatozoa. Unusual large and long characteristics of the
accessory fibers were involved in generating the gently curved bends and a low
beat frequency. Examination of the motility parameters of the flagellar beat of
the activated and hyperactivated spermatozoa attached to a slide glass by their
heads revealed that there were two beating modes: a frequency-curvature dependent
mode in the activated flagellar beat and a nearly constant frequency mode in the
hyperactivated flagellar beat. The hyperactivated flagellar beat was
characterized by sharp bends in the proximal midpiece and a low beat frequency.
The sharp bends in the proximal midpiece were induced by the increase in the
total length of the microtubule sliding at the flagellar base. The rate of
microtubule sliding (sliding velocity) in the axoneme remained almost constant in
the flagellar beat of both the activated and hyperactivated spermatozoa.
Comparison of the sliding velocity in Suncus, golden hamster, monkey, and sea
urchin sperm flagella with their stiffness suggests that the sliding velocity is
determined by the stiffness at the flagellar base and that the same sliding
microtubule system functions in both mammalian and echinoderm spermatozoa.
PMID- 17034048
TI - Meiotic competence and acetylation pattern of UV light classified mouse antral
oocytes after meiotic arrest with isobutylmethylxanthine.
AB - Chromatin transformation from a diffused or NSN configuration to a compacted or
SN shape that forms a ring around the nucleolus is regarded as one of the
modifications necessary for successful embryonic development. But the process of
the transformation is poorly understood. In this study we cultured mouse antral
oocytes under meiotic arrest with IBMX for periods between 3 and 24 hr. We
observed the chromatin status of the oocytes before and after culture under UV
illumination. We reported here that the NSN configured oocytes transformed
temporally through an intermediate form into the SN configuration while under
meiotic arrest in vitro. Meiotic rate was improved in the NSN oocytes after the
meiotic arrest but decreased in the SN oocytes. We also reported that chromatin
of both the NSN and SN oocytes was acetylated and the two groups underwent the
same pattern of H4/K5 deacetylation during meiotic maturation. We hypothesized
that the transformation of mouse oocyte from the NSN to SN type may be time
rather than oocyte size specific and the abrupt deacetylation of NSN oocyte
during spontaneous maturation may explain its poor meiotic and developmental
competence.
PMID- 17034049
TI - Glycoproteins of the vitelline envelope of Amphibian oocyte: biological and
molecular characterization of ZPC component (gp41) in Bufo arenarum.
AB - The vitelline envelope (VE) participates in sperm-egg interactions during the
first steps of fertilization. In Bufo arenarum, this envelope is composed of at
least four glycoproteins, with molecular masses of 120, 75, 41, and 38 kDa and
molar ratio of 1:1.3:7.4:4.8, respectively. These components were isolated and
covalently coupled to silanized glass slides in order to study their sperm
binding capacity. When considering the molar ratio of the glycoproteins in the
egg-envelope and assuming that each protein is monovalent for sperm, the assay
showed that gp41 and gp38 possess 55 and 25% of total sperm-binding activity. We
obtained a full-length cDNA of gp41 (ZPC), comprising a sequence for 486 amino
acids, with 43.3% homology with Xenopus laevis ZPC. As in the case of mammalian
ZP3 and Xenopus ZPC, Bufo ZPC presented a furin-like (convertase) and a C
terminal transmembrane domain (TMD) reflecting common biosynthetic and secretory
pathways. As it was reported for some fishes, we obtained evidence that suggests
the presence of more than one zpc gene in Bufo genome, based on different partial
cDNA sequences of zpc, Southern blots and two-dimensional SDS-PAGE of
deglycosylated egg-envelope components. As far as we are aware, this is the first
observation of the presence of different zpc genes in an Amphibian species.
PMID- 17034050
TI - Heat stress-induced apoptosis in porcine in vitro fertilized and parthenogenetic
preimplantation-stage embryos.
AB - Decades worth of research have consistently shown the adverse effects of elevated
temperatures on reproductive parameters of livestock species. The objective of
this study was to evaluate the developmental and apoptotic responses of porcine
in vitro fertilized (IVF) and parthenogenetically activated (PA) embryos heat
stressed at the late 1-cell stage. Embryos were heat stressed (HS) at 42 degrees
C for 9 hr starting 22 hr after insemination or artificial activation stimulus.
Non heat-stressed (NHS) control embryos were maintained at 39 degrees C for the
duration of the experiments. TUNEL staining on Day 5 of development demonstrated
that heat stress elicited a significant apoptotic response in IVF embryos (45.6%
of HS embryos and 26.7% of NHS embryos were apoptotic; P<0.05), but not in PA
embryos (51.1% and 39.9% for HS and NHS embryos, respectively; P>0.1). And, while
IVF embryos were highly susceptible to heat-induced developmental perturbations
(20.6% and 8.8% development to blastocyst for NHS and HS embryos, respectively;
P<0.05), elevated temperatures did not affect blastocyst rates in PA embryos
(22.2% for NHS PA embryos and 21.2% for HS PA embryos; P>0.1). These findings
indicate that, as in other systems studied, IVF pig embryos are directly affected
adversely by heat stress conditions. Parthenogenetic embryos, though, appear to
be surprisingly tolerant of the elevated temperatures. The differences between
IVF and PA embryos in their response to heat stress warrants further
investigation.
PMID- 17034051
TI - Estimation of melting points of organic compounds-II.
AB - A model for calculation of melting points of organic compounds from structure is
described. The model utilizes additive, constitutive and nonadditive,
constitutive molecular properties to calculate the enthalpy of melting and the
entropy of melting, respectively. Application of the model to over 2200
compounds, including a number of drugs with complex structures, gives an average
absolute error of 30.1 degrees.
PMID- 17034052
TI - Release of gentamicin from a tricalcium phosphate bone implant.
AB - The impregnation and elution of gentamicin antibiotic from a commercially
available porous beta-tricalcium phosphate (TCP) bone implant material (Vitoss,
Orthovita, Inc.) was investigated in vitro. Sustained local antibiotic release is
an attractive method for the prevention of infection following surgery. The
purpose of this study was to evaluate the use of the naturally forming clot that
occurs within a porous tissue scaffold when combined with autologous blood or
bone marrow aspirate (BMA) as a method for achieving controlled drug delivery.
The diffusion of antibiotic from porous TCP scaffolds was studied using water,
clotted blood, or BMA as impregnating fluids. Incorporation of the drug into the
porous scaffold using clotted blood or BMA as a binder produced slowed release
relative to aqueous impregnated and dried samples. Modifications were made to the
elution method to simulate restricted diffusion due to surrounding clotted blood,
tissue, or bone that would occur in vivo. These modified methods simulated
release in a surgical site and showed long release profiles, with significant
amounts of antibiotic being released for up to 2 weeks. We concluded that adding
gentamicin with autologous BMA is a promising method of controlling drug release.
PMID- 17034053
TI - Novel epididymis-specific mRNAs downregulated by HE6/Gpr64 receptor gene
disruption.
AB - Targeted disruption of the epididymis-specific HE6/Gpr64 receptor gene in mice
led to male infertility. In order to characterize the phenotype at a molecular
level, we compared the gene expression patterns of wild type (wt) versus knockout
(KO) caput epididymides. The caput region of KO males, although morphologically
normal, nevertheless showed an aberrant expression pattern. Combining micro array
analysis, differential library screening, Northern blot analysis and quantitative
RT-PCR, we found that the knockout of the HE6/Gpr64 receptor was mainly
associated with the downregulation of genes specific to the initial segment. The
list of KO downregulated transcripts comprised Enpp2/autotaxin, the lipocalins 8
and 9, the beta-defensin Defb42, cystatins 8 and 12, as well as the membrane
proteins Adam (A Disintegrin And Metalloprotease) 28, claudin-10, EAAC1, and the
novel Me9. Clusterin/ApoJ and osteopontin/Spp1 mRNAs, on the other hand, were
upregulated in the KO tissues. The Me9 transcript was studied in further detail,
and we report here a cluster of related epididymis-specific genes. Me9 is
specifically expressed in the initial segment and is representative of a novel
and highly conserved mammalian gene family. The family consists of single-exon
genes only; intron-containing paralogs have not yet been ascertained. The cloned
cDNA sequences predicted hydrophobic polytopic membrane proteins containing the
DUF716 motif. Protein expression was shown in the rodent caput epididymidis but
remained uncertain in primates.
PMID- 17034054
TI - Isolation and characterization of embryonic stem cell-like cells from in vitro
produced buffalo (Bubalus bubalis) embryos.
AB - This study was carried out to isolate and characterize buffalo embryonic stem
(ES) cell-like cells from in vitro-produced embryos. Inner cell mass (ICM) cells
were isolated either mechanically or by enzymatic digestion from 120 blastocysts
whereas 28 morulae were used for the isolation of blastomeres mechanically. The
ICM cells/ blastomeres were cultured on mitomycin-C-treated feeder layer. Primary
cell colony formation was higher (P < 0.05) for hatched blastocysts (73.1%,
30/41) than that for early/expanded blastocysts (25.3%, 20/79). However, no
primary cell colonies were formed when blastomeres obtained from morulae were
cultured. Primary colonies were formed in 14.1% (12/85) of intact blastocyst
culture, which was significantly lower (P < 0.05) than that of 41.6% for ICM
culture. These colonies were separated by enzymatic or mechanical disaggregation.
Using mechanical disaggregation method, the cells remained undifferentiated and
two buffalo ES cell-like cell lines (bES1, bES2) continued to grow in culture up
to eight passages. However, disassociation through enzymatic method resulted in
differentiation. Undifferentiated cells exhibited stem cell morphological
features, normal chromosomal morphology, and expressed specific markers such as
alkaline phosphatase (AP) and Oct-4. Cells formed embryoid bodies (EBs) in
suspension culture; extended culture of EBs resulted in formation of cystic EBs.
Following prolonged in vitro culture, these cells differentiated into several
types of cells including neuron-like and epithelium-like cells. Furthermore, the
vitrified-thawed ES cell-like cells also exhibited typical stem cell
characteristics. In conclusion, buffalo ES cell-like cells could be isolated from
in vitro-produced blastocysts and maintained in vitro for prolonged periods of
time.
PMID- 17034055
TI - Supracondylar process with a high origin of the radial artery.
PMID- 17034056
TI - C3, C4, C5, keep you alive, or do they?
PMID- 17034057
TI - The iliacus minimus muscle.
PMID- 17034058
TI - Caroticoclinoid foramen with interclinoid osseous bar.
PMID- 17034059
TI - Bilateral lateral bipartite levator palpebrae superioris muscles.
PMID- 17034060
TI - The association between birth season and future development of childhood asthma.
AB - The aim of this study was to examine a possible association between birth season
(date of birth) and future development of asthma in children. A case-control
study was designed to include asthmatic children aged 2-7 years, living in the
city of Beer-Sheva, in southern Israel, registered in one pediatric center.
Controls were healthy children matched for age and registered at the same clinic.
Demographic data, past medical history, and asthma history and severity were
collected using the computerized medical charts and asthma registry. A structured
telephone questionnaire was used to complete the data. Children with a history of
prematurity or chronic significant illness were excluded from the study. Sixty
six children and 69 controls were enrolled in the study. There were significantly
more males in the asthmatic group compared to controls (P = 0.003). History of
bronchiolitis or recurrent wheezing episodes in the first year, family history of
asthma, and Middle-Eastern origin were significantly more common among asthmatic
children than controls (P < 0.001). Asthmatic children were more likely to be
born between March and June and least likely to be born between October and
December, compared to controls (P < 0.05). Multivariate logistic regression
analysis revealed three variables to be independent significant risk factors for
development of asthma: birth season between March and June, acute bronchiolitis
or recurrent wheezing episodes during first year of life, and male gender. Birth
season during late winter and spring is associated with asthma during childhood.
PMID- 17034061
TI - Insulin and obstructive sleep apnea in obese Chinese children.
AB - OBJECTIVE: In adults, obstructive sleep apnea (OSA) is associated with insulin
resistance and dyslipidemia. We aimed to establish correlation between OSA, serum
lipid profile, and insulin levels in obese snoring children. METHODS: Consecutive
obese children with habitual snoring were recruited. They underwent physical
examination, overnight polysomnography (PSG), and metabolic studies. OSA was
diagnosed if apnea hypopnea index (AHI) > 1.0, and cases were considered to have
moderate to severe OSA if AHI > 10. RESULTS: Ninety-four obese subjects with
habitual snoring were studied. Seventy-three subjects were male and the median
age of the studied group was 12.0 years (IQR 9.7-13.9). None of the subjects had
active cardiopulmonary disease, and the BMI values of our subjects were >95th
percentile using local reference charts. Sixty subjects had OSA, 47 being mild,
and 13 being moderate to severe OSA. Multiple logistic regression analysis
revealed that saturation nadir and insulin levels were significantly associated
with OSA. CONCLUSION: OSA is prevalent among obese children with habitual snoring
and insulin is independently associated with the condition. Its role in the
cardiovascular complications of childhood sleep apnea is worthy of further
exploration.
PMID- 17034063
TI - Outcome in the real-world of coronary high-risk intervention with drug-eluting
stents (ORCHID) -- a single-center study comparing Cypher sirolimus-eluting with
Taxus paclitaxel-eluting stents.
AB - OBJECTIVE: We present real world experience from a single center registry
comparing the 6-month outcome of percutaneous coronary intervention (PCI) in
unselected high-risk individuals using either sirolimus-eluting (SES) or
paclitaxel-eluting stents (PES). METHODS/RESULTS: We compared clinical outcome at
6 months follow-up in two cohorts of 156 consecutive patients (total n = 312) who
underwent SES (June 2002-February 2003) and PES (march 2003-July 2003)
implantation. The primary endpoint was a composite of major adverse cardiac
events (MACE). Baseline clinical characteristics were well matched. The 6-month
target vessel revascularization (TVR) rates were 1.9% (SES) and 2.6% (PES) and
MACE rates were similar in the two groups (SES 4.5% vs. PES 3.2%, P = NS). In the
PES group, intervention for multivessel disease, bifurcation lesions and in small
vessels was more common, and for in-stent restenosis less common, reflecting the
impact of drug eluting stents on indications for PCI. The incidence of sub-acute
stent thrombosis, related to inadequate antiplatelet therapy in 3 of the 6 cases,
was 0.95% with no difference between the two groups. CONCLUSION: This study
confirms the safety and efficacy of SES and PES in unselected high risk patients
undergoing PCI. Clinical outcomes of both stents are equivalent at 6 months with
low rates of MACE and TVR. These data provide important complementary information
to forthcoming randomized studies.
PMID- 17034065
TI - Survivin expression levels as independent predictors of survival for osteosarcoma
patients.
AB - Survivin expression has been detected in various cancers and correlations have
been recognized between the level of expression of this gene in tumors and
prognosis. However, the aforementioned authors did not evaluate correlations
between prognosis and survivin expression levels using surgically resected
samples. In this study, we retrospectively investigated outcomes by examining the
correlations between expression of this gene and clinicopathological parameters.
Biopsy and resected specimens from which paraffin-embedded tissues could be
extracted, were available from 16 patients in our hospital. We used the RT-PCR
method and conducted a densitometric analysis to determine the ratio of survivin
relative to h-GAPDH as an internal marker. Expression of survivin mRNA was
detected in all samples. There was a significant negative correlation between
survivin expression levels and duration of follow up, in months, using the
Spearman's rank for the initial biopsy samples (rho=-0.775, p<0.01) and those
obtained after chemotherapy (rho=-0.687, p<0.01). Moreover, Cox multivariate
regression identified the survivin expression levels in both biopsy and post
chemotherapy samples as independent predictors of survival. We conclude that
survivin levels in both initial biopsy and post-chemotherapy samples are useful
prognostic indicators.
PMID- 17034064
TI - Efficacy of intracoronary nicardipine in the treatment of no-reflow during
percutaneous coronary intervention.
AB - OBJECTIVES: The goal of this study was to evaluate the safety and efficacy of
nicardipine in reversing no-reflow during percutaneous coronary intervention
(PCI). BACKGROUND: No-reflow is a common complication of PCI in patients with
acute coronary syndromes or venous bypass graft disease. Although nicardipine has
an attractive pharmacological profile and has been used clinically to treat no
reflow, there is a paucity of published data regarding its effectiveness in this
setting. METHODS: We conducted a retrospective analysis of 72 consecutive
patients who received intracoronary nicardipine to reverse no-reflow during
coronary intervention. Qualitative TIMI flow grade and quantitative TIMI frame
count methods were used to assess the efficacy of nicardipine. RESULTS: A mean of
460 +/- 360 mcg of intracoronary nicardipine was used. No-reflow was successfully
reversed with complete restoration of TIMI 3 flow in 71 of 72 patients (98.6%).
TIMI flow grade improved from 1.65 +/- 0.53 prior to nicardipine to 2.97 +/- 0.24
after treatment (P < 0.001). TIMI frame count decreased from 57 +/- 40 at the
time of no-reflow to 15 +/- 12 after nicardipine administration (P < 0.001).
Nicardipine therapy was well tolerated without adverse hemodynamic or
chronotropic effects. CONCLUSIONS: In this largest series to date, intracoronary
nicardipine was demonstrated to be a safe and highly effective pharmacological
agent to reverse no-reflow during PCI.
PMID- 17034066
TI - Proceedings of the 2nd International Workshop on Vaccine Adjuvants and
Glycoconjugates, Varadero, Cuba, 11-15 April 2004.
PMID- 17034067
TI - Influences on advancement of nursing knowledge.
PMID- 17034068
TI - Nursing and medicine: continuing challenges.
PMID- 17034069
TI - Evaluation of diagnostic tests for infectious diseases: general principles.
PMID- 17034070
TI - Evaluation of rapid diagnostic tests: malaria.
PMID- 17034071
TI - The dialogue within nursing theory-guided practice: a frontier of knowledge and
development.
PMID- 17034072
TI - Readers' responses and author's reply to "cultural awareness: a prescription for
more effective medicine".
PMID- 17034073
TI - Centres of excellence in cardiology: the Hammersmith Hospital.
PMID- 17034074
TI - Commentary: vitamin A supplementation for reducing the risk of mother-to-child
transmission of HIV infection.
PMID- 17034075
TI - Commentary: vitamin A supplementation for reducing the risk of mother-to-child
transmission of HIV infection.
PMID- 17034076
TI - Mensuration, Mendel, and a 19th century public health justification for US
imperialism.
PMID- 17034077
TI - Legacy: inside the Chernobyl exclusion zone.
PMID- 17034078
TI - Visualization of localized intense optical fields in single gold-nanoparticle
assemblies and ultrasensitive Raman active sites.
AB - We demonstrate visualization of localized intense electromagnetic fields in real
space in well-tailored dimeric and trimeric gold nanospheres by using near-field
optical techniques. With two-photon induced luminescence and Raman measurements,
we show that the electric field is confined at an interstitial site in the
aggregate. We also demonstrate optical switching operations for the electric
field localized sites in the trimer structure.
PMID- 17034079
TI - Biotemplated nanopatterning of planar surfaces with molecular motors.
AB - We report on the generation of nanometer-wide, non-topographical patterns of
proteins on planar surfaces. In particular, we used the regular lattice of
reconstituted microtubules as template structures to specifically bind and
transfer kinesin-1 and nonclaret disjunctional motor proteins. The generated
tracks, which comprise dense and structurally oriented arrays of functional motor
proteins, proved to be highly efficient for the guiding of microtubule
transporters.
PMID- 17034080
TI - Electron transfer dynamics of bistable single-molecule junctions.
AB - We present transport measurements of single-molecule junctions bridged by a
molecule with three benzene rings connected by two double bonds and with thiol
end-groups that allow chemical binding to gold electrodes. The I-V curves show
switching behavior between two distinct states. By statistical analysis of the
switching events, we show that a 300 meV mode mediates the transition between the
two states. We propose that breaking and reformation of a S-H bond in the contact
zone between molecule and electrode explains the observed bistability.
PMID- 17034081
TI - Impact ionization can explain carrier multiplication in PbSe quantum dots.
AB - The efficiency of conventional solar cells is limited because the excess energy
of absorbed photons converts to heat instead of producing electron-hole pairs.
Recently, efficient carrier multiplication has been observed in semiconductor
quantum dots. In this process, a single, high-energy photon generates multiple
electron-hole pairs. Rather exotic mechanisms have been proposed to explain the
efficiency of carrier multiplication in PbSe quantum dots. Using atomistic
pseudopotential calculations, we show here that the more conventional impact
ionization mechanism, whereby a photogenerated electron-hole pair decays into a
biexciton in a process driven by Coulomb interactions between the carriers, can
explain both the rate (<<1 ps) and the energy threshold ( approximately 2.2 times
the band gap) of carrier multiplication, without the need to invoke alternative
mechanisms.
PMID- 17034082
TI - Bundle-shaped cyclodextrin-Tb nano-supramolecular assembly mediated by C60:
intramolecular energy transfer.
AB - A bundle-shaped nano-supramolecular assembly possessing numerous luminescent
cyclodextrin-Tb polyads and photosensitizing C(60) units has been constructed
through the end-to-end inclusion complexation of cyclodextrin cavities with
C(60)s, and its properties have been comprehensively characterized. Further
investigations on the luminescence properties of the cyclodextrin-Tb polyad and
the bundle-shaped assembly demonstrate that a pyridine --> Tb --> C(60)
intramolecular energy transfer process is operative when a solution of the
assembly is exposed to UV light.
PMID- 17034083
TI - Level structure of InAs quantum dots in two-dimensional assemblies.
AB - The electronic level structure of colloidal InAs quantum dots (QDs) in two
dimensional arrays, forming a QD-solid system, was probed using scanning
tunneling spectroscopy. The band gap is found to reduce compared to that of the
corresponding isolated QDs. Typically, the electron (conduction-band) ground
state red shifts more than the hole (valence-band) ground state. This is assigned
to the much smaller effective mass of the electrons, resulting in stronger
electron delocalization and larger coupling between electron states of
neighboring QDs compared to the holes. This is corroborated by comparing these
results with those for InAs and CdSe nanorod assemblies, manifesting the effects
of the electron effective mass and arrangement of nearest neighbors on the band
gap reduction. In addition, in InAs QD arrays, the levels are broadened, and in
some cases their discrete level structure was nearly washed out completely and
the tunneling spectra exhibited a signature of two-dimensional density of states.
PMID- 17034084
TI - Scanned gate microscopy of a one-dimensional quantum dot.
AB - We analyze electrostatic interaction between a sharp conducting tip and a thin
one-dimensional wire, e.g., a carbon nanotube, in a scanned gate microscopy (SGM)
experiment. The problem is analytically tractable if the wire resides on a thin
dielectric substrate above a metallic backgate. The characteristic spatial scale
of the electrostatic coupling to the tip is equal to its height above the
substrate. Numerical simulations indicate that imaging of individual electrons by
SGM is possible once the mean electron separation exceeds this scale (typically,
a few tens of nm). Differences between weakly and strongly invasive SGM regimes
are pointed out.
PMID- 17034085
TI - Optically pumped surface-emitting lasing using self-assembled block-copolymer
distributed Bragg reflectors.
AB - A thin-film organic laser cavity using a block-copolymer-based one-dimensional
(1D) photonic crystal was fabricated. Polymeric distributed Bragg reflectors
(DBRs) were prepared through the self-assembly of a lamellar-forming poly(styrene
b-isoprene) (PS-b-PI) diblock copolymer having a 1D photonic stop band
overlapping with the fluorescence spectrum of a gain medium. Optically pumped
surface-emitting lasing was obtained using poly(methyl methacrylate) (PMMA) doped
with 1,4-di-(2-methylstyryl)benzene (Bis-MSB) as an organic gain medium and the
polymeric self-assembled DBR as a spectral-band selective feedback element.
PMID- 17034086
TI - Early use of PbS nanotechnology for an ancient hair dyeing formula.
AB - Lead-based chemistry was initiated in ancient Egypt for cosmetic preparation more
than 4000 years ago. Here, we study a hair-dyeing recipe using lead salts
described in text since Greco-Roman times. We report direct evidence about the
shape and distribution of PbS nanocrystals that form within the hair during
blackening. It is remarkable that the composition and supramolecular organization
of keratins can control PbS nanocrystal growth inside a hair.
PMID- 17034087
TI - Properties of a versatile nanoparticle platform contrast agent to image and
characterize atherosclerotic plaques by magnetic resonance imaging.
AB - The need for more specific and selective contrast agents for magnetic resonance
imaging motivated us to prepare a new nanoparticle agent based on high-density
lipoproteins (HDL). This second generation contrast agent can be prepared in
three different ways. The HDL nanoparticles (rHDL) were fully characterized by
FPLC and gel electrophoresis. The flexibility of the platform also allows us to
incorporate optical probes into rHDL for localization ex vivo by confocal
fluorescence microscopy. The contrast-agent-containing nanoparticles were
injected into mice that develop atherosclerotic lesions. Magnetic resonance
imaging of the animals showed clear enhancement of the atherosclerotic plaques.
PMID- 17034088
TI - In vivo molecular probing of cellular compartments with gold nanoparticles and
nanoaggregates.
AB - Surface-enhanced Raman (SERS) signatures were measured from single living cells
at different times after the uptake of gold nanoparticles. The spectra are
indicative of chemical changes in the environment of the nanostructures over
time. The increase of the SERS signal strength and parallel TEM studies indicate
the formation of nanoaggregates providing optimum SERS enhancement for
ultrasensitive probing inside the endosomal compartment. The results have
implications for medical and biotechnology applications of SERS nanosensors in
cells.
PMID- 17034089
TI - Electrokinetic energy conversion efficiency in nanofluidic channels.
AB - We theoretically evaluate the prospect of using electrokinetic phenomena to
convert hydrostatic energy to electrical power. An expression is derived for the
energy conversion efficiency of a two-terminal fluidic device in terms of its
linear electrokinetic response properties. For a slitlike nanochannel of constant
surface charge density, we predict that the maximum energy conversion efficiency
occurs at low salt concentrations. An analytic expression for the regime of
strong double-layer overlap reveals that the efficiency depends only on the ratio
of the channel height to the Gouy-Chapman length, and the product of the
viscosity and the counterion mobility. We estimate that an electrokinetic energy
conversion device could achieve a maximum efficiency of 12% for simple monovalent
ions in aqueous solution.
PMID- 17034090
TI - Electrical conductance of molecular junctions by a robust statistical analysis.
AB - We propose an objective and robust method to extract the electrical conductance
of single molecules connected to metal electrodes from a set of measured
conductance data. Our method roots in the physics of tunneling and is tested on
octanedithiol using mechanically controllable break junctions. The single
molecule conductance values can be deduced without the need for data selection.
PMID- 17034091
TI - Tailoring the interfaces between nematic liquid crystal emulsions and aqueous
phases via layer-by-layer assembly.
AB - We report the assembly of polyelectrolyte multilayer (PEM) films at the
interfaces of thermotropic liquid crystal (LC) droplets dispersed in an aqueous
phase. Exposure of PEM-coated droplets to surfactant slowed the bipolar-to-radial
ordering transition of the LCs by 2 orders of magnitude relative to naked
droplets. This shows that PEMs can be used to influence the interactions of
analytes with the LC cores of the droplets, allowing tuning of the LC emulsion
sensing properties.
PMID- 17034093
TI - Complex buckling instability patterns of nanomembranes with encapsulated gold
nanoparticle arrays.
AB - The nanomechanical properties of micropatterned nanomembranes containing gold
nanoparticle microarrays were investigated with the buckling instability method.
An unusual, complex pattern of buckling instability was observed for the
nanoscale polymeric films under compressive stresses. An intriguing two-stage
wrinkling was observed for these nanoscale films with spatially correlated
instabilities. Two concurrent strain-dependent buckling modes were observed above
a certain critical strain. Transformation from conventional transversal buckling
mode to zigzag buckling is attributed to the development of the biaxial stress
along the boundary lines for micropatterned areas. The binary buckling pattern
observed here allowed the "one-shot" evaluation of the elastic moduli of two
compositionally different regions (with and without gold nanoparticles).
PMID- 17034092
TI - The role of thickness transitions in convective assembly.
AB - Here we examine the microscopic details of convective assembly, a process in
which thin colloidal crystals are deposited on a substrate from suspensions of
nearly monodisperse spheres. Previously, such crystals have been shown to exhibit
a strong tendency toward the face-centered cubic structure, which is difficult to
explain on thermodynamic grounds. Using real-time microscopic visualization,
electron microscopy, and scanning confocal microscopy, we obtain clues about the
crystallization mechanism. Our results indicate that the regions at which a
growing crystal transitions from n to n + 1 layers can play an important and
previously unrecognized role in the crystallization. For thin crystals, we show
both from experiment and through simple modeling that these transition regions
can generate specific crystal structures. In thicker crystals, the
crystallization is more complicated, but the transition regions must still be
considered before a complete understanding of convective assembly can be
obtained.
PMID- 17034094
TI - Shock-induced localized amorphization in metallic nanorods with strain-rate
dependent characteristics.
AB - Classical force-field simulations were used to study the tensile shock-induced
response of metallic nanorods. The nanorods were found to amorphize at strain
rate amorphization limits of 1.6% ps(-1) for a 4.0-nm-diameter platinum (Pt)
nanorod and 1.2% ps(-1) for a 4.0-nm-diameter gold (Au) nanorod, with a length-to
diameter ratio of 3. Highly localized necking was observed at mid-depth of the
nanorods at about 2.0% ps(-1). As the strain rates were increased further, the
neck bifurcated away from the mid-depth toward the nanorod ends, resulting in
multiple necks at 4.0% ps(-1) and 3.0% ps(-1) for Pt and Au, respectively. At
strain rates of above 6.0% ps(-1), end delamination took place. The longitudinal
wave propagation equation was adequate to explain and predict the location of the
appearance of necks along the nanorod.
PMID- 17034095
TI - Catalytic membranes prepared using layer-by-layer adsorption of
polyelectrolyte/metal nanoparticle films in porous supports.
AB - Layer-by-layer adsorption of polyelectrolytes and gold nanoparticles within
porous supports provides a convenient method for forming catalytic membranes. The
polyelectrolyte film effectively immobilizes the gold nanoparticles without
inhibiting access to catalytic sites, as shown by the similar rate constants for
nanoparticle-catalyzed 4-nitrophenol reduction in solution and in membranes.
Modified alumina membranes reduce >99% of 0.4 mM 4-nitrophenol at linear flow
rates of 0.98 cm/s, and the modification process is also applicable to track
etched polycarbonate supports.
PMID- 17034096
TI - Synthesis and electrical characterization of silver nanobeams.
AB - By slowing the rate of atomic addition to singly twinned seeds, we have grown
silver nanobeams with lengths of 3-30 mum, widths ranging from 17 to 70 nm, and a
width to thickness ratio of 1.4. The well-defined dimensions, smooth surface, and
crystallinity of nanobeams make them promising candidates for studying the
effects of size on electron transport. With a simple method that allows rapid
characterization of single nanobeams, we find that even the thinnest nanobeams
largely retain the low resistivity of bulk silver. Nanobeams can support
remarkably high current densities of up to 2.6 x 10(8) A cm(-2) before the
conduction path is broken by the formation of a nanogap.
PMID- 17034097
TI - Direct patterning of three-dimensional periodic nanostructures by surface-plasmon
assisted nanolithography.
AB - The technical applications of three-dimensional (3D) nanostructures demand a
fabrication technique that is convenient and yet offers design flexibility. We
describe here a nanofabrication technique called surface-plasmon-assisted three
dimensional nanolithography (3D-SPAN). By utilizing optical near-field
interference patterns generated by surface plasmons (SPs), we have fabricated
different 2D/3D periodic polymeric nanostructures in a typical photolithography
setup. We have also shown here that the nanostructures fabricated by 3D-SPAN can
be controlled easily in terms of size, layout, and defects by designing the SPAN
mask. Because of its design flexibility and fabrication convenience, 3D-SPAN
could be used to develop "photonics on a chip", where signal processing is
carried out by photons instead of electrons and be extended to other applications
of direct-writing 3D functional nanostructures.
PMID- 17034098
TI - Nucleation and melting from nanovoids.
AB - Melting in solids containing nanovoids is studied via molecular dynamics
simulation, and the finite size effects are treated with different size systems.
For the first time, we have found four typical stages in void melting that are
different from the melting of bulk materials and nanoparticles. Melting in each
of the stages is governed by the interplay among different thermodynamic
mechanisms arising from the changes in the interfacial free energies, the
curvature of the interface, and the elastic energy induced by the density change
at melting. As a result, the local melting temperatures show a strong dependence
on the void size, which is the root cause of the observed complex hierarchical
melting sequence.
PMID- 17034099
TI - Formation of rectangularly shaped Pd/Au bimetallic nanorods: evidence for
competing growth of the Pd shell between the 110 and 100 side facets of Au
nanorods.
AB - In this letter, we report the competing growth of a Pd shell on the {110} and
{100} facets of Au nanorods (Au NRs). This results in the disappearance of
unstable {110} facets and the formation of rectangularly shaped Pd/Au bimetallic
nanorods that show only four stable {100} side surfaces. The energy minimization
to a more stable morphology is believed to be the driving force for the formation
of the rectangular shape of the Pd shell.
PMID- 17034100
TI - Ultrafast vibrationally-induced dephasing of electronic excitations in PbSe
quantum dots.
AB - Vibrationally induced pure-dephasing of electronic states in PbSe quantum dots
(QDs) at room temperature is investigated using two independent theoretical
approaches based on the optical response function and semiclassical formalisms.
Both approaches predict dephasing times of around 10 fs and reproduce the
recently measured homogeneous linewidths of optical absorption well. Because
dephasing slows down with increasing cluster size, the dephasing times calculated
for the small clusters correspond to the lower end of the experimental data. The
dephasing is almost independent of the electronic excitation energy and occurs
faster for biexcitons than single excitons. The dephasing time is roughly
proportional to the square root of the mass of the lighter atom (Se), suggesting
that dephasing should be faster in PbS and slower in PbTe relative to PbSe. Core
atoms produce stronger dephasing than surface atoms. In the collective
description, pure-dephasing occurs via low-frequency acoustic modes, in support
of the elastic QD model of dephasing. Because the electron-phonon coupling in
PbSe QDs is relatively weak compared to other semiconductor nanocrystals, fast
vibrationally induced dephasing can be expected in semiconductor QDs in general.
PMID- 17034101
TI - In situ observation of nanograin rotation and deformation in nacre.
AB - Nacre is a natural nanocomposite material with superior mechanical strength and
toughness. What roles do the nanoscale structures play in the inelasticity and
toughening of nacre? Can we learn from this to produce nacre-like nanocomposites?
Here we report in situ dynamic atomic force microscope observations of nacre with
aragonite nanograins (nanoparticles) of an average grain size of 32 nm, which
show that nanograin rotation and deformation are the two prominent mechanisms
contributing to energy dissipation in nacre. The biopolymer spacing between the
nanograins facilitates the grain rotation process. The aragonite nanograins in
nacre are not brittle but deformable.
PMID- 17034102
TI - All-nanoparticle thin-film coatings.
AB - All-nanoparticle thin-film coatings that exhibit antireflection, antifogging
(superhydrophilicity), and self-cleaning properties have been prepared via layer
by-layer deposition of TiO(2) and SiO(2) nanoparticles. The porosity and chemical
composition of the coatings were determined using a simple method that is based
on ellipsometry and does not require any assumptions about the refractive indices
of the constituent nanoparticles. The presence of nanopores in the TiO(2)/SiO(2)
nanoparticle coatings results in superhydrophilicity as well as antireflection
properties. The superhydrophilicity of contaminated coatings could also be
readily recovered and retained after ultraviolet irradiation.
PMID- 17034103
TI - Strain-induced self organization of metal-insulator domains in single-crystalline
VO2 nanobeams.
AB - We investigated the effect of substrate-induced strain on the metal-insulator
transition (MIT) in single-crystalline VO(2) nanobeams. A simple nanobeam
substrate adhesion leads to uniaxial strain along the nanobeam length because of
the nanobeam's unique morphology. The strain changes the relative stability of
the metal (M) and insulator (I) phases and leads to spontaneous formation of
periodic, alternating M-I domain patterns during the MIT. The spatial periodicity
of the M-I domains can be modified by changing the nanobeam thickness and the
Young's modulus of the substrate.
PMID- 17034104
TI - Bulk quantities of single-crystal silicon micro-/nanoribbons generated from bulk
wafers.
AB - This Letter demonstrates a strategy for producing bulk quantities of high
quality, dimensionally uniform single-crystal silicon micro- and nanoribbons from
bulk silicon (111) wafers. The process uses etched trenches with controlled
rippled structures defined on the sidewalls, together with angled evaporation of
masking materials and anisotropic wet etching of the silicon, to produce
multilayer stacks of ribbons with uniform thicknesses and lithographically
defined lengths and widths, across the entire surface of the wafer. Ribbons with
thicknesses between tens and hundreds of nanometers, widths in the micrometer
range, and lengths of up to several centimeters, can be produced, in bulk
quantities, using this approach. Printing processes enable the layer by layer
transfer of organized arrays of such ribbons to a range of other substrates. Good
electrical properties (mobilities approximately 190 cm(2)V(-1)s(-1), on/off
>10(4)) can be achieved with these ribbons in thin film type transistors formed
on plastic substrates, thereby demonstrating one potential area of application.
PMID- 17034105
TI - Controlled replication of butterfly wings for achieving tunable photonic
properties.
AB - The fine structure of the wing scale of a Morpho Peleides butterfly was examined
carefully, and the entire configuration was completely replicated by a uniform
Al(2)O(3) coating through a low-temperature ALD process. An inverted structure
was achieved by removing the butterfly wing template at high temperature, forming
a polycrystalline Al(2)O(3) shell structure with precisely controlled thickness.
Other than the copy of the morphology of the structure, the optical property,
such as the existence of PBG, was also inherited by the alumina replica.
Reflection peaks at the violet/blue range were detected on both original wings
and their replica, while a simple alumina coating shifted the reflection peak to
longer wavelength because of the change of periodicity and refraction index. The
alumina replicas also exhibited similar functional structures as waveguide and
beam splitter, which may be used as the building blocks for photonic ICs with
high reproducibility and lower fabrication cost compared to traditional
lithography techniques.
PMID- 17034106
TI - Three-dimensional self-assembly of spherical block copolymer domains into V
shaped grooves.
AB - The self-assembly of a spherical-morphology block copolymer into V-shaped grooves
has been investigated. Although spherical morphology block copolymers typically
form a bcc sphere array in bulk, the V groove promotes the formation of a well
ordered fcc close-packed sphere array with the (111) planes of the array parallel
to the groove walls. The sphere size in the block copolymer adjusts depending on
the commensurability between the periodicity of the block copolymer and the film
thickness within the V groove. The top surface of the close-packed array,
parallel to the substrate, shows a square symmetry, unlike the hexagonal symmetry
seen in monolayers of spherical domains, which may provide a useful geometry for
block copolymer lithography.
PMID- 17034107
TI - Profiling the near field of a plasmonic nanoparticle with Raman-based molecular
rulers.
AB - The enhanced local optical fields at the surface of illuminated metallic
nanoparticles and nanostructures are of intense fundamental and technological
interest. Here we report a self-consistent measurement of the spatial extent of
the fringing field above a plasmonic nanoparticle surface. Bifunctional DNA-based
adsorbate molecules are used as nanoscale optical rulers, providing two distinct
surface enhanced Raman scattering signals that vary independently in intensity as
a function of distance from the nanoparticle surface. While the measurement
technique is calibrated on gold nanoshell surfaces with controlled and
predictable electromagnetic nanoenvironments, this approach is broadly adaptable
to a wide range of plasmonic geometries.
PMID- 17034108
TI - Site-specific fabrication and epitaxial conversion of functional oxide nanodisk
arrays.
AB - Nanodisk arrays of technologically important magnetic (CoFe(2)O(4)) and
ferroelectric (BaTiO(3)) oxides are fabricated on diverse substrates with well
defined size and separation using the soft-eBL approach. We demonstrate that
below a certain pattern size, the as-deposited amorphous nanodisks can be readily
converted into dense, single-crystal form that exhibit cube-on-cube heteroepitaxy
with respect to the underlying single-crystal substrate. Such single-crystal
disks show well-defined truncated-pyramid morphology that is consistent with
Wulff construction. The mechanism of morphology development with the pattern size
change is discussed. Localized characterization of the crystallinity, chemical
composition, and magnetic behavior of the CFO nanodisk patterns are carried out
using analytical transmission electron microscopy and magnetic force microscopy.
Such solution-based epitaxial conversion of patterned arrays of multifunctional
oxides has potential for viable cost-effective technological applications.
PMID- 17034109
TI - Toward intelligent nanosize bioreactors: a pH-switchable, channel-equipped,
functional polymer nanocontainer.
AB - To develop an intelligent sensor-effector functionality on the nanoscale, a pH
switchable, controlled nanoreactor based on amphiphilic copolymer membranes was
built. The nanovesicles were equipped with bacterial transmembrane ompF pore
proteins and the pH-sensitive enzyme acid phosphatase, resulting in a switchable
substrate processing at pH 4-6.5. Ideal pH and substrate concentrations for the
reaction were determined experimentally. In future, the reactor might be used for
self-regulating targeted diagnostic and therapeutic applications in medicine.
PMID- 17034110
TI - Mesoporous membrane templated by a polymeric bicontinuous microemulsion.
AB - We demonstrate a facile method for preparing a novel nanoporous material with an
isotropic, three-dimensionally continuous pore structure from a polymeric
bicontinuous microemulsion precursor, which consists of two immiscible
homopolymers and the corresponding diblock copolymer. The protocol for the
generation of nanopores is selective cross-linking of one domain with the
subsequent removal of the other domain by solvent dissolution.
PMID- 17034111
TI - 1D nanofabrication with a micrometer-sized laser spot.
AB - A simple laser-assisted procedure for the fabrication of functional organic
nanostructures is demonstrated. Native silicon samples are coated with
alkylsiloxane monolayers and patterned with a focused beam of an Ar(+) laser
(lambda = 514 nm). After patterning, the coating is chemically functionalized
following a robust preparation scheme. Despite a laser spot diameter of about 2.5
mum, this routine allows for the fabrication of well-confined organosiloxane
stripes with widths below 100 nm. As shown, these structures provide a versatile
means for building ordered surface architectures of nanoscopic components. In
particular, gold nanoparticles (d = 16 nm) self-assemble into one-dimensional
arrangements, such as single chains.
PMID- 17034112
TI - Interpretation of stochastic events in single molecule conductance measurements.
AB - The electrical conductance of a series of thiol-terminated alkanes, (1,6
hexanedithiol (HDT), 1,8-octanedithiol (ODT), and 1,10-decanedithol (DDT)) was
measured using a modified scanning tunneling microscope break junction technique.
The interpretation of data obtained in this technique is complicated due to
multiple effects such as microscopic details of the metal-molecule junctions,
superposition of tunneling currents, and conformational changes in the molecules.
A new method called the last-step analysis (LSA) is introduced here to clarify
the contribution of these effects. In direct contrast to previous work, LSA does
not require any data preselection, making the results less subjective and more
reproducible. Finally, LSA was used to obtain the conductance of single molecules
(HDT, (3.6 x 10(-4))G(o); ODT, (4.4 x 10(-5))G(o); DDT, (5.7 x 10(-6))G(o)). The
tunneling decay parameter (beta) was calculated, and it was found to be
approximately 1.0 per carbon atom.
PMID- 17034113
TI - Control of droplet size in liquid nanodispensing.
AB - In this Letter, the phenomena and parameters governing the nanoscale dispensing
of liquid through an apertured atomic force microscope probe milled by focused
ion beam lithography are characterized in detail. We show that the size of
deposited droplets can be reproducibly defined by controlling the aperture size
on the probe and the surface energies of both tip outer wall and substrate
surface. On the basis of these findings, tips with aperture diameter as small as
35 nm enabled the deposition of regular arrays of nanodroplets with diameter down
to 70 nm on an alkylamine-modified surface. The fine control of droplet volumes
down to a few tens of zeptoliters (10(-21)L) provides a unique tool for creating
devices and probing the fundamentals of wetting at the nanometer scale.
PMID- 17034114
TI - Periodic ZnO nanorod arrays defined by polystyrene microsphere self-assembled
monolayers.
AB - We demonstrate a low-cost and effective method to fabricate hexagonally
patterned, vertically aligned ZnO nanorod arrays. Selective wet-etching is used
to develop the catalyzing gold particle hexagonal pattern with the aid of a
polystyrene microsphere self-assembled monolayer. The gold particles have tunable
sizes independent of the polystyrene microsphere's diameter and are inherently
round in shape. Each ZnO rod is grown individually from a catalyzing site via
catalyst-initiated epitaxy, and the original hexagonal periodicity is well
preserved. The rods have flat ends, and the diameters of the rods can be
controlled well by the amount of source materials. This method provides a
promising way to create ZnO one-dimensional nanostructures for applications as
two-dimensional photonic crystal, sensor arrays, nanolaser arrays, and
optoelectronic devices.
PMID- 17034115
TI - Size effects on the mechanical behavior of nanoporous Au.
AB - Recent nanomechanical tests on submicron metal columns and wires have revealed a
dramatic increase in yield strength with decreasing sample size. Here, we
demonstrate that nanoporous metal foams can be envisioned as a three-dimensional
network of ultrahigh-strength nanowires, thus bringing together two seemingly
conflicting properties: high strength and high porosity. Specifically, we
characterized the size-dependent mechanical properties of nanoporous gold using a
combination of nanoindentation, column microcompression, and molecular dynamics
simulations. We find that nanoporous gold can be as strong as bulk Au, despite
being a highly porous material, and that the ligaments in nanoporous gold
approach the theoretical yield strength of Au.
PMID- 17034116
TI - Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl
2 proteins.
AB - A structure-based approach was employed to design a new class of small-molecule
inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a
K(i) value of 290 nM and also to Bcl-xL and Mcl-1 with high affinities. Compound
5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC(50)
value of 200 nM and effectively induces apoptosis in a dose-dependent manner.
PMID- 17034117
TI - Discovery of 6-N,N-bis(2,2,2-trifluoroethyl)amino- 4-trifluoromethylquinolin
2(1H)-one as a novel selective androgen receptor modulator.
AB - The androgen receptor is a member of the extended family of nuclear receptors and
is widely distributed throughout the body. Androgen therapy is used to compensate
for low levels of the natural hormones testosterone (T) and dihydrotestosterone
and consists of administration of T, prodrugs thereof, or synthetic androgens.
However, currently available androgens have many drawbacks. We identified 6
dialkylamino-4-trifluoromethylquinolin-2(1H)-ones as orally available tissue
selective androgen receptor modulators.
PMID- 17034118
TI - Macrocyclic inhibitors of beta-secretase: functional activity in an animal model.
AB - A macrocyclic inhibitor of beta-secretase was designed by covalently cross
linking the P1 and P3 side chains of an isophthalamide-based inhibitor.
Macrocyclization resulted in significantly improved potency and physical
properties when compared to the initial lead structures. More importantly, these
macrocyclic inhibitors also displayed in vivo amyloid lowering when dosed in a
murine model.
PMID- 17034119
TI - Discovery of phenyl acetic acid substituted quinolines as novel liver X receptor
agonists for the treatment of atherosclerosis.
AB - A structure-based approach was used to optimize our new class of quinoline LXR
modulators leading to phenyl acetic acid substituted quinolines 15 and 16. Both
compounds displayed good binding affinity for LXRbeta and LXRalpha and were
potent activators in LBD transactivation assays. The compounds also increased
expression of ABCA1 and stimulated cholesterol efflux in THP-1 cells. Quinoline
16 showed good oral bioavailability and in vivo efficacy in a LDLr knockout mouse
model for lesions.
PMID- 17034120
TI - Benzopyrans are selective estrogen receptor beta agonists with novel activity in
models of benign prostatic hyperplasia.
AB - Benzopyran selective estrogen receptor beta agonist-1 (SERBA-1) shows potent,
selective binding and agonist function in estrogen receptor beta (ERbeta) in
vitro assays. X-ray crystal structures of SERBA-1 in ERalpha and beta help
explain observed beta-selectivity of this ligand. SERBA-1 in vivo demonstrates
involution of the ventral prostate in CD-1 mice (ERbeta effect), while having no
effect on gonadal hormone levels (ERalpha effect) at 10x the efficacious dose,
consistent with in vitro properties of this molecule.
PMID- 17034121
TI - Acylguanidines as small-molecule beta-secretase inhibitors.
AB - BACE1 is an aspartyl protease responsible for cleaving amyloid precursor protein
to liberate Abeta, which aggregates leading to plaque deposits implicated in
Alzheimer's disease. We have identified small-molecule acylguanidine inhibitors
of BACE1. Crystallographic studies show that these compounds form unique hydrogen
bonding interactions with the catalytic site aspartic acids and stabilize the
protein in a flap-open conformation. Structure-based optimization led to the
identification of potent analogs, such as 10d (BACE1 IC(50) = 110 nM).
PMID- 17034122
TI - Configurationally restricted bismacrocyclic CXCR4 receptor antagonists.
AB - A zinc(II) containing configurationally restricted analogue of bismacrocyclic
cyclam-type CXCR4 chemokine receptor antagonists has been synthesized and shown
to adopt only one configuration in solution. The single crystal X-ray structure
reveals favorable binding to acetate via a bidentate chelation that can be
related to the proposed interaction with aspartate on the receptor protein
surface. The zinc(II) complex is highly active against HIV infection in vitro.
PMID- 17034123
TI - Synthesis and antiviral activity of 5-substituted cytidine analogues:
identification of a potent inhibitor of viral RNA-dependent RNA polymerases.
AB - As part of our studies of lethal viral mutagens, a series of 5-substituted
cytidine analogues were synthesized and evaluated for antiviral activity. Among
the compounds examined, 5-nitrocytidine was effective against poliovirus (PV) and
coxsackievirus B3 (CVB3) and exhibited greater activity than the clinically
employed drug ribavirin. Instead of promoting viral mutagenesis, 5-nitrocytidine
triphosphate inhibited PV RNA-dependent RNA polymerase (K(d) = 1.1 +/- 0.1
microM), and this inhibition is sufficient to explain the observed antiviral
activity.
PMID- 17034124
TI - Determination of the binding mode of thienopyrimidinedione antagonists to the
human gonadotropin releasing hormone receptor using structure-activity
relationships, site-directed mutagenesis, and homology modeling.
AB - We have investigated the specific interactions of a series thienopyrimidinediones
with the gonadotropin-releasing hormone receptor (GnRH-R). Competitive
radioligand binding assays were used to determine the effect of several mutants
on nonpeptide binding. Distinct interactions were observed in two separate
regions: the N-terminal end of TM7 and the C-terminal end of TM6. The effects of
mutants at D302((7.32)) and H306((7.36)) suggest that these residues are part of
a hydrogen-bond network important for anchoring the nonpeptides. Structure
activity relationships indicated urea substituents on the 6-(4-aminophenyl) group
with a trans conformational preference bind with high affinity and are sensitive
to D302((7.32)) mutations. Another interaction area was found between the N
benzyl-N-methylamino substituent and L300((6.68)) and Y290((6.58)). These
interaction sites facilitated the derivation of a model in which a representative
member of the series was docked into GnRH-R. The model is consistent with known
SAR and illuminates inconsistencies with previous hypotheses regarding how this
series interacts with the receptor.
PMID- 17034125
TI - Extra precision glide: docking and scoring incorporating a model of hydrophobic
enclosure for protein-ligand complexes.
AB - A novel scoring function to estimate protein-ligand binding affinities has been
developed and implemented as the Glide 4.0 XP scoring function and docking
protocol. In addition to unique water desolvation energy terms, protein-ligand
structural motifs leading to enhanced binding affinity are included: (1)
hydrophobic enclosure where groups of lipophilic ligand atoms are enclosed on
opposite faces by lipophilic protein atoms, (2) neutral-neutral single or
correlated hydrogen bonds in a hydrophobically enclosed environment, and (3) five
categories of charged-charged hydrogen bonds. The XP scoring function and docking
protocol have been developed to reproduce experimental binding affinities for a
set of 198 complexes (RMSDs of 2.26 and 1.73 kcal/mol over all and well-docked
ligands, respectively) and to yield quality enrichments for a set of fifteen
screens of pharmaceutical importance. Enrichment results demonstrate the
importance of the novel XP molecular recognition and water scoring in separating
active and inactive ligands and avoiding false positives.
PMID- 17034126
TI - New efficient substrates for semicarbazide-sensitive amine oxidase/VAP-1 enzyme:
analysis by SARs and computational docking.
AB - Structure activity relationships for semicarbazide-sensitive amine
oxidase/vascular adhesion protein-1 (SSAO/VAP-1) were studied using a library of
arylalkylamine substrates, with the aim of contributing to the discovery of more
efficient SSAO substrates. Experimental data were contrasted with computational
docking studies, thereby allowing us to examine the mechanism and substrate
binding affinity of SSAO and thus contribute to the discovery of more efficient
SSAO substrates and provide a structural basis for their interactions. We also
built a model of the mouse SSAO structure, which provides several structural
rationales for interspecies differences in SSAO substrate selectivity and reveals
new trends in SSAO substrate recognition. In this context, we identified novel
efficient substrates for human SSAO that can be used as a lead for the discovery
of antidiabetic agents.
PMID- 17034127
TI - Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an
isoindolinone scaffold.
AB - From a set of weakly potent lead compounds, using in silico screening and small
library synthesis, a series of 2-alkyl-3-aryl-3-alkoxyisoindolinones has been
identified as inhibitors of the MDM2-p53 interaction. Two of the most potent
compounds, 2-benzyl-3-(4-chlorophenyl)-3-(3-hydroxypropoxy)-2,3-dihydroisoindol-1
one (76; IC(50) = 15.9 +/- 0.8 microM) and 3-(4-chlorophenyl)-3-(4-hydroxy-3,5
dimethoxybenzyloxy)-2-propyl-2,3-dihydroisoindol-1-one (79; IC(50) = 5.3 +/- 0.9
microM), induced p53-dependent gene transcription, in a dose-dependent manner, in
the MDM2 amplified, SJSA human sarcoma cell line.
PMID- 17034128
TI - In-situ synthesis of a tacrine-triazole-based inhibitor of acetylcholinesterase:
configurational selection imposed by steric interactions.
AB - Recently, researchers have used acetylcholinesterase (AChE) as a reaction vessel
to synthesize its own inhibitors. Thus, 1 (syn-TZ2PA6), a femtomolar AChE
inhibitor, which is formed in a 1:1 mixture with its anti-isomer by solution
phase reaction from 3 (TZ2) and 4 (PA6), can be synthesized exclusively inside
the AChE gorge. Our computational approach based on quantum mechanical/molecular
mechanical (QM/MM) calculations, molecular dynamics (MD), and targeted molecular
dynamics (TMD) studies answers why 1 is the sole product in the AChE environment.
Ab initio QM/MM results show that the reaction in the AChE gorge occurs when
3/azide and 4/acetylene are extended in a parallel orientation. An MD simulation
started from the final structure of QM/MM calculations keeps the azide's and
acetylene's parallel orientations intact for 10 ns of simulation time. A TMD
simulation applied on an antiparallel azide-acetylene conformation flips the
acetylene easily to bring it to a position that is parallel to azide. A second
set of QM/MM calculations performed on this flipped structure generates a similar
minimum-energy path as obtained previously. Even a TMD simulation carried out on
a parallel azide-acetylene conformation could not deform their parallel
arrangement. All of these results, thus, imply that inside the AChE gorge, the
azide group of 3 and the acetylene group of 4 always remain parallel, with the
consequence that 1 is the only product. The architecture of the gorge plays an
important role in this selective formation of 1.
PMID- 17034129
TI - Recursive partitioning for the prediction of cytochromes P450 2D6 and 1A2
inhibition: importance of the quality of the dataset.
AB - The purpose of this study was to explore the use of detailed biological data in
combination with a statistical learning method for predicting the CYP1A2 and
CYP2D6 inhibition. Data were extracted from the Aureus-Pharma highly structured
databases which contain precise measures and detailed experimental protocol
concerning the inhibition of the two cytochromes. The methodology used was
Recursive Partitioning, an easy and quick method to implement. The building of
models was preceded by the evaluation of the chemical space covered by the
datasets. The descriptors used are available in the MOE software suite. The
models reached at least 80% of Accuracy and often exceeded this percentage for
the Sensitivity (Recall), Specificity, and Precision parameters. CYP2D6 datasets
provided 11 models with Accuracy over 80%, while CYP1A2 datasets counted 5 high
accuracy models. Our models can be useful to predict the ADME properties during
the drug discovery process and are indicated for high-throughput screening.
PMID- 17034130
TI - Comparative binding energy analysis considering multiple receptors: a step toward
3D-QSAR models for multiple targets.
AB - Comparative binding energy analysis, a technique to derive receptor-based three
dimensional quantitative structure-activity relationships (3D-QSAR), is herein
extended to consider both affinity and selectivity in the derivation of the QSAR
model. The extension is based on allowing multiple structurally related receptors
to enter the X-matrix employed in the derivation of the structure-activity model.
As a result, a single model common to all of them is obtained that considers both
intra- and inter-receptor affinity differences for a given congeneric series. We
applied the technique to a series of 88 3-amidinophenylalanines, binding to
thrombin, trypsin, and factor Xa (fXa). A single predictive regression model for
the three receptors involving 202 complexes, with a leave-one out (LOO) cross
validated Q(2) of 0.689, was obtained, and selectivity requirements were
investigated. We find that total or partial occupancy of any of the three main
pockets in the binding site (D-site, P-site, and the rim of the S1-site) leads to
higher affinity across the family. However, the fact that thrombin can make
stronger interactions in the P-site, as a result of its exclusive 60-loop, makes
of this site a specificity pocket for this thrombin. Occupancy of the D-site
leads to more active inhibitors toward fXa for the same reason, but the model
does not highlight strongly the D-box because inhibitors are too short to fully
occupy it. Negative charge density in the neighborhood of position 88 (a Lys
insertion in thrombin) is found to be a determinant for thrombin recognition.
These results were consistent with previous studies on selectivity in the
thrombin/trypsin/fXa system.
PMID- 17034131
TI - Conformationally restricted dipeptide amides as potent and selective neuronal
nitric oxide synthase inhibitors.
AB - Four new conformationally restricted analogues of a potent and selective neuronal
nitric oxide synthase inhibitor, l-nitroargininyl-l-2,4-diaminobutyramide (1),
have been synthesized. N(alpha)-Methyl and N(alpha)-benzyl derivatives (3 and 4,
respectively) of 4-N-(l-Arg(NO(2))-trans-4-amino-l-prolineamide (2) are also
selective inhibitors, but the potency and selectivity of 3 are weak. Analogue 4
has only one-third the potency and one-half to one-third the selectivity of 2
against iNOS (inducible nitric oxide synthase) and eNOS (endothelial nitric oxide
synthase), respectively. 3-N-(l-Arg(NO)(2))-trans-3-amino-l-prolineamide (6) is
as potent an inhibitor of nNOS (neuronal nitric oxide synthase) as 2; selectivity
for nNOS over iNOS is half of that for 2, but the selectivity for nNOS over eNOS
is almost double that for 2. The corresponding cis-isomer (5) is a weak inhibitor
of nNOS. These results are supported by computer modeling.
PMID- 17034132
TI - Impact of species-dependent differences on screening, design, and development of
MAO B inhibitors.
AB - The impact of species-dependent differences between human and rat MAO B on
inhibitor screening was evidenced for two classes of compounds, coumarin and 5H
indeno[1,2-c]pyridazin-5-one derivatives. All examined compounds have shown a
greater inhibitor potency toward human MAO B than toward rat MAO B. Moreover, no
correlation was found between human and rat pIC(50) values. These divergences
have important implications for the design and development of drugs involved in
the MAO B metabolic pathway, suggesting that results obtained using rat enzyme
cannot be extrapolated to human CNS, a priori. Indeed, the selection of a hit
compound for lead generation could be different using human rather than rat
enzyme. Moreover, the influence of substituents on the in vitro inhibition of
human MAO B was markedly different between homogeneous series of coumarin and 5H
indeno[1,2-c]pyridazin-5-one derivatives, suggesting different binding modes, a
hypothesis clearly supported by molecular docking simulations of inhibitors into
the active site of human MAO B.
PMID- 17034133
TI - Synthesis and structure-activity relationships of carbazole sulfonamides as a
novel class of antimitotic agents against solid tumors.
AB - Two series of carbazole sulfonamides related to Combretastatin A4 (1) were
synthesized and evaluated for antiproliferative activity. Thirteen of the 26 new
sulfonamides exhibited IC(50) values of <1 muM against CEM leukemia cells. Five
compounds were evaluated against a panel of eight human tumor cell lines. 9-Ethyl
N-(3,4,5-trimethoxyphenyl)-carbazole-3-sulfonamide (11a) showed significant
antitumor activity in two human xenograft models (MCF-7 and Bel-7402).
Preliminary studies with 11a showed that the mode of action involves arrest of M
phase cell cycle and induction of apoptosis by increasing expression of p53 and
promoting bcl-2 phosphorylation. Unexpectedly, 11a only weakly inhibits tubulin
polymerization, which suggests that the mode of action of 11a differs from 1 and
involves an unidentified target(s). Also, the SAR information gleaned from ring A
substituted analogues varies significantly from that of 1. Carbazole sulfonamides
are a novel promising class of antimitotic agents with clinical development
potential.
PMID- 17034134
TI - Synthesis and evaluation of indenoisoquinoline topoisomerase I inhibitors
substituted with nitrogen heterocycles.
AB - In connection with an ongoing investigation of indenoisoquinoline topoisomerase I
(Top1) inhibitors as potential therapeutic agents, the pharmacophore possessing
di(methoxy) and methylenedioxy substituents was held constant, and new
derivatives were synthesized with nitrogen heterocycles appended to the lactam
side chain. Compounds were evaluated for Top1 inhibition and for cytotoxicity in
the National Cancer Institute's human cancer cell screen. Some of the more potent
derivatives were also screened for in vivo activity in a hollow fiber assay. The
results of these studies indicate that lactam substituents possessing nitrogen
heterocycles can provide highly cytotoxic compounds with potent Top1 inhibition.
Molecular modeling of these compounds in complex with DNA and Top1 suggests that
some of the lactam substituents are capable of interacting with the DNA base
pairs above and below the site of intercalation and/or with Top1 amino acid
residues, resulting in increased biological activity.
PMID- 17034136
TI - Identification of selective, nonpeptidic nitrile inhibitors of cathepsin s using
the substrate activity screening method.
AB - The substrate activity screening method, a substrate-based fragment
identification and optimization method for the development of enzyme inhibitors,
was previously applied to cathepsin S to obtain low nanomolar 1,4-disubstituted
1,2,3-triazole-based aldehyde inhibitors (Wood, W. J. L.; Patterson, A. W.;
Tsuruoka, H.; Jain, R. K.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 15521
15527). Replacement of the metabolically labile aldehyde pharmacophore with the
nitrile pharmacophore provided inhibitors with moderate potency for cathepsin S.
The inhibitors showed good selectivity over cathepsins B and L but no selectivity
over cathepsin K. X-ray structures of two crystal forms (1.5 and 1.9 A) of a
complex between cathepsin S and a triazole inhibitor incorporating a chloromethyl
ketone pharmacophore guided the design of triazole substrates with increased
cleavage efficiency and selectivity for cathepsin S over cathepsins B, L, and K.
Conversion of select substrates to nitrile inhibitors yielded a low molecular
weight (414 Da) and potent (15 nM) cathepsin S inhibitor that showed >1000-fold
selectivity over cathepsins B, L, and K.
PMID- 17034135
TI - Enzyme specific activation of benzoquinone ansamycin prodrugs using
HuCC49DeltaCH2-beta-galactosidase conjugates.
AB - To activate prodrugs for cancer treatment, an anti-TAG-72 antibody
(HuCC49DeltaCH2) was used for delivery of an activation enzyme (beta
galactosidase) to specifically activate a geldanamycin prodrug (17-AG-C2-Gal)
against colon cancer. The geldanamycin prodrug 17-AG-C2-Gal was synthesized by
coupling a galactose-amine derivative with geldanamycin at the C-17 position.
Molecular docking with two different programs (Affinity and Autodock) showed that
the prodrug (17-AG-C2-Gal) was unable to bind to Hsp90; however, the product (17
AG-C2), enzymatically cleaved by beta-galactosidase conjugate, bound to Hsp90 in
a similar way as geldanamycin and 17-AG. The computational docking results were
further confirmed in experimental testing by the tetrazolium [3-(4,5
dimethythiazol-2-yl)]-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
assay and mass spectrometry. HuCC49DeltaCH2 was chemically conjugated to beta
galactosidase. The antibody-enzyme conjugate was able to target tumor antigen TAG
72 with the well-preserved enzymatic activity to activate 17-AG-C2-Gal prodrug.
The released active drug 17-AG-C2 was demonstrated to induce up to 70% AKT
degradation and enhance anticancer activity by more than 25-fold compared to the
prodrug.
PMID- 17034137
TI - Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier
protein reductase from Mycobacterium tuberculosis.
AB - In view of the worldwide spread of multidrug resistance of Mycobacterium
tuberculosis, there is an urgent need to discover antituberculosis agent with
novel structures. InhA, the enoyl acyl carrier protein reductase (ENR) from M.
tuberculosis, is one of the key enzymes involved in the mycobacterial fatty acid
elongation cycle and has been validated as an effective antimicrobial target. We
report here the discovery, through high-throughput screening, of a series of
pyrrolidine carboxamides as a novel class of potent InhA inhibitors. Crystal
structures of InhA complexed with three inhibitors have been used to elucidate
the inhibitor binding mode. The potency of the lead compound was improved over
160-fold by subsequent optimization through iterative microtiter library
synthesis followed by in situ activity screening without purification. Resolution
of racemic mixtures of several inhibitors indicate that only one enantiomer is
active as an inhibitor of InhA.
PMID- 17034138
TI - Conformational analysis of an alpha3beta1 integrin-binding peptide from
thrombospondin-1: implications for antiangiogenic drug design.
AB - The integrin alpha3beta1 plays important roles in development, angiogenesis, and
the pathogenesis of cancer, suggesting potential therapeutic uses for antagonists
of this receptor. Recently, an alpha3beta1 integrin-binding site was mapped to
residues 190-201 (FQGVLQNVRFVF) of the N-terminal domain of the secreted protein
thrombospondin-1 (TSP1). This sequence displays diverse biological activities in
vitro and inhibits angiogenesis in vivo. Herein we describe the NMR solution
conformation of this segment in both water and dodecylphosphocholine micelles.
While essentially unstructured in water, a more well-defined conformation is
populated in micelles, particularly in the C-terminal half of the peptide and
correlated with increased biological activity of the micellar peptide. The data
suggested that the residues that are critical for biological activity are
contained in a structurally well-defined segment of the peptide. These data
support the role of the NVR motif as a required element of full-length TSP1 for
specific molecular recognition by the alpha3beta1 integrin.
PMID- 17034139
TI - Pediatric erythromycins: a comparison of the properties of erythromycins A and B
2'-ethyl succinates.
AB - The antibiotic erythromycin A is generally administered to children as a
suspension of the pro-drug erythromycin A 2'-ethyl succinate. The success of the
pro-drug depends on (a) elimination of the unacceptably bitter taste of free
erythromycin, (b) its stability against stomach acid, and (c) its smooth (base
catalyzed) hydrolysis in the body to yield active erythromycin. We have
investigated the rates and pathways of acid-catalyzed degradation and base
catalyzed hydrolysis of the 2'-ethyl succinates of erythromycins A and B.
Esterification does not protect the drugs against acid-catalyzed degradation in
solution; however, erythromycin B 2'-ethyl succinate is much more stable than the
corresponding erythromycin A ester, degrading nearly 40 times more slowly. The
rates of base-catalyzed hydrolysis in conditions mimicking the blood stream are
similar for the two pro-drugs. We conclude that erythromycin B 2'-ethyl succinate
is an attractive prospect as a pediatric erythromycin pro-drug.
PMID- 17034140
TI - Synthesis, structure-activity relationships, and antitumor studies of 2
benzoxazolyl hydrazones derived from alpha-(N)-acyl heteroaromatics.
AB - Recently we have described the antitumor activities of 2-benzoxazolylhydrazones
derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious
analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2
acylpyridine and alpha-(N)-acetyldiazine/quinoline groups have been synthesized.
The 2-acylpyridyl hydrazones inhibited in vitro cell proliferation in the nM
range, whereas the hydrazones derived from the alpha-(N)
acetyldiazines/quinolines inhibited cell growth in the muM range. Compounds
tested in the NCI-60 cell assay were effective inhibitors of leukemia, colon, and
ovarian cancer cells. E-13k [N-benzoxazol-2-yl-N'-(1-isoquinolin-3-yl-ethylidene)
hydrazine] inhibited the proliferation of MCF-7 breast carcinoma cells more
efficiently than nontransformed MCF-10A cells. It is not transported by P
glycoprotein and a weak MRP substrate. Increased concentrations of serum or
alpha(1)-acid glycoprotein did not reduce the antiproliferative activity of the
compound. In the in vivo hollow fiber assay, E-13k achieved a score of 24, with a
net cell kill of OVCAR-3 (ovarian) and SF2-95 (CNS) tumor cells.
PMID- 17034141
TI - Structure-activity relationship of quinoline derivatives as potent and selective
alpha(2C)-adrenoceptor antagonists.
AB - Starting from two acridine compounds identified in a high-throughput screening
campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and
tested for their properties on the human alpha(2)-adrenoceptor subtypes
(alpha(2A), alpha(2B), and alpha(2C)). A number of compounds with good antagonist
potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities
over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4
dimethylpiperazin-1-yl)phenylamino]quinolin-3-yl}methanol 6j had an antagonist
potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for,
the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship
identified a number of structural features, the most critical of which was an
absolute need for a substituent in the 3-position of the quinoline ring. The 3
position on the piperazine ring was also found to play an appreciable role, as
substitutions in that position exerted a significant and stereospecific
beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing
the piperazine ring proved difficult, with 1,4-diazepanes representing the only
viable alternative.
PMID- 17034142
TI - Synthesis of a highly pure lipid core peptide based self-adjuvanting triepitopic
group A streptococcal vaccine, and subsequent immunological evaluation.
AB - We have developed a highly pure, self-adjuvanting, triepitopic Group A
Streptococcal vaccine based on the lipid core peptide system, a vaccine delivery
system incorporating lipidic adjuvant, carrier, and peptide epitopes into a
single molecular entity. Vaccine synthesis was performed using native chemical
ligation. Due to the attachment of a highly lipophilic adjuvant, addition of 1%
(w/v) sodium dodecyl sulfate was necessary to enhance peptide solubility in order
to enable ligation. The vaccine was synthesized in three steps to yield a highly
pure product (97.7% purity) with an excellent overall yield. Subcutaneous
immunization of B10.BR (H-2(k)) mice with the synthesized vaccine, with or
without the addition of complete Freund's adjuvant, elicited high serum IgG
antibody titers against each of the incorporated peptide epitopes.
PMID- 17034143
TI - Identification and optimization of anthranilic sulfonamides as novel, selective
cholecystokinin-2 receptor antagonists.
AB - A high throughput screening approach to the identification of selective
cholecystokinin-2 receptor (CCK-2R) ligands resulted in the discovery of a novel
series of antagonists, represented by 1-[2-[(2,1,3-benzothiadiazol-4
ylsulfonyl)amino]-5-chlorobenzoyl]-piperidine (1; CCK-2R, pK(I) = 6.4).
Preliminary exploration of the structure-activity relationships around the
anthranilic ring and the amide and sulfonamide moieties led to a nearly 50-fold
improvement of receptor affinity and showed a greater than 1000-fold selectivity
over the related cholecystokinin-1 receptor. Pharmacokinetic evaluation led to
the identification of 4-[4-iodo-2-[(5-quinoxalinylsulfonyl)amino]benzoyl]
morpholine, 26d, a compound that demonstrates promising pharmacokinetic
properties in the rat and dog with respect to plasma clearance and oral
bioavailability and is a potent inhibitor in vivo of pentagastrin-stimulated acid
secretion in the rat when dosed orally.
PMID- 17034144
TI - Structure-activity relationship studies on a novel series of (S)-2beta
substituted 3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogues for
in vivo investigation.
AB - In general, 3alpha-(diphenylmethoxy)tropane (benztropine)-based dopamine uptake
inhibitors do not demonstrate cocaine-like pharmacological activity in models of
psychostimulant abuse and have been proposed as potential medications for the
treatment of cocaine addiction. However, several (S)-2-carboalkoxy-substituted
3alpha-[bis(4-fluorophenyl)methoxy]tropane analogues were discovered to stimulate
locomotor activity and substitute in subjects trained to discriminate cocaine,
suggesting a role of the 2-position substituent in mediating these cocaine-like
actions. Herein, we describe the synthesis of a series of novel N- and 2
substituted-3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogues.
Most of these analogues demonstrated high affinity binding to the dopamine
transporter (DAT; K(i) = 1.8-40 nM), and selectivity over the other monoamine
transporters and muscarinic M(1) receptors. When the (S)-2-carboalkoxy
substituent was replaced with (S)-2-ethenyl, the resulting analogue 11
demonstrated the highest DAT binding affinity in the series (K(i) = 1.81 nM) with
DAT selectivity over serotonin transporters (SERT; 989-fold), norepinephrine
transporters (NET; 261-fold) and muscarinic receptors (90-fold). When the 4'-F
groups of compounds 5 (K(i) = 2.94 nM) and 8 (K(i) = 6.87 nM) were replaced with
4'-Cl in the (S)-2-carboalkoxy series, DAT binding affinities were slightly
reduced (K(i) = 12.6 and 14.6 nM for 6 and 7, respectively), yet inhibition of
dopamine uptake potency remained comparably high (IC(50) range = 1.5-2.5 nM).
Interestingly, the 4'-Cl analogue (+/-)-6 substituted less in rats trained to
discriminate cocaine than the 4'-F analogue (+/-)-5. These studies demonstrate
that manipulation of the 2-, N-, and 3-position substituents in the 3alpha
(diphenylmethoxy)tropane class of dopamine uptake inhibitors can result in
ligands with high affinity and selectivity for the DAT, and distinctive in vivo
pharmacological profiles that cannot be predicted by their effects in vitro.
PMID- 17034145
TI - Comblike dendrimers containing Tn antigen modulate natural killing and induce the
production of Tn specific antibodies.
AB - Comblike glycodendrimers were prepared by the chemoselective ligation of cysteine
modified glycopeptides (1-7) with a 3-maleimidopropionate-modified linear
synthetic carrier (8). Glycodendrimers bearing mono-, di-, or tri-Tn clusters (9
11) were tested as inhibitors using plant and mammalian lectins. In the former
group, the Codium fragile lectin showed moderate discrimination among 9, 10, and
11. In the latter group, A and B isoforms of rat NKR-P1 lectin strongly
discriminated between 9 and 10. 10 caused a 4-fold increase in killing of the NK
resistant tumor cell lines at concentrations as low as 10(-8) M. Surprisingly, 11
interacted exclusively with the rat NKR-P1B isoform and inhibited efficiently
natural killing in both rats and humans, even in the presence of the activating
compounds 9 and 10. Dinitrophenol haptenization or influenza virus hemagglutinin
T-cell epitope conjugation increased the immunogenicity of the parent compounds
and resulted in the production of Tn specific antibodies.
PMID- 17034146
TI - Dopamine/serotonin receptor ligands. 13: Homologization of a benzindoloazecine
type dopamine receptor antagonist modulates the affinities for dopamine D(1)-D(5)
receptors.
AB - Enlarging the 10-membered ring of 7-methyl-6,7,8,9,14,15-hexahydro-5H-indolo[3,2
f][3]benzazecine (1, LE 300) yielded two homologue antagonists. Their affinities
and inhibitory activities at D(1)-D(5) receptors were measured by radioligand
binding experiments and a functional Ca(2+) assay. Compared to 1, phenylpropyl
homologue 3 was superior in selectivity and affinity for the D(5) subtype (K(i) =
0.6 nM), whereas the affinity of the indolylpropyl homologue 2 for all subtypes
decreased. Compounds 2, 3, 10, 11, 17, and 18 are derivatives of novel
heterocyclic ring systems.
PMID- 17034147
TI - 2-amino and 2'-aminocombretastatin derivatives as potent antimitotic agents.
AB - A novel series of 2-amino and 2'-aminocombretastatin derivatives were synthesized
and evaluated for antitumor activity. Several compounds had excellent
antiproliferative activity as inhibitors of tubulin polymerization. Compounds 11,
20, and 21 with IC(50) values of 1.6, 1.7, and 1.8 microM, respectively,
exhibited more potent inhibition of tubulin polymerization than colchicine and
approximately as active as combretastatin A-4. They also displayed
antiproliferative activity with an IC(50) values ranging from 11 to 44 nM in a
variety of human cell lines from different organs. Structure activity
relationship information suggests that the NH(2) substituent at the 2-position of
either ring A or ring B in combretastatin molecular skeleton may play an
important role in the bioactivity of this series of compounds.
PMID- 17034148
TI - Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]
4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent,
selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV,
useful for the treatment of diabetes.
AB - Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug
class for the treatment of type 2 diabetes. Structure-activity studies of
substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the
discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and
DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM)
and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate,
ABT-279, that is orally available, efficacious, and remarkably safe in
preclinical safety studies.
PMID- 17034149
TI - Structural basis for the structure-activity relationships of peroxisome
proliferator-activated receptor agonists.
AB - Type 2 diabetes has rapidly reached an epidemic proportion becoming a major
threat to global public health. PPAR agonists have emerged as a leading class of
oral antidiabetic drugs. We report a structure biology analysis of novel indole
based PPAR agonists to explain the structure-activity relationships and present a
critical analysis of reasons for change in selectivity with change in the
orientation of the same scaffolds. The results would be helpful in designing
novel PPAR agonists.
PMID- 17034150
TI - Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-amino 5
aryl thiophenes as a new class of tubulin inhibitors.
AB - 2-(3',4',5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives
were synthesized and evaluated for antiproliferative activity, inhibition of
tubulin polymerization, and cell cycle effects. SARs were elucidated with various
substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at
the para-position of the 5-phenyl group showed antiproliferative activity in the
order of F=CH(3) > OCH(3)=Br=NO(2) > CF(3)=I > OEt. Several of these compounds
led to arrest of HL-60 cells in the G2/M phase of the cell cycle and induction of
apoptosis.
PMID- 17034151
TI - Much improved upper limit for the rate constant for the reaction of O2+ with N2.
AB - The rate constant for the reaction of O2+ with N2 to produce NO+ plus NO has been
measured at 423, 523, and 623 K in a turbulent ion flow tube. Much improved upper
limits for this reaction at the three temperatures are 2, 4, and 10x10(-21) cm3 s
1, respectively. These results should render this reaction irrelevant when
modeling all plasmas involving atmospheric gases.
PMID- 17034152
TI - The kinetics of thermal decomposition of 1-butyl-3-methylimidazolium
hexafluorophosphate.
AB - It is demonstrated that 1-butyl-3-methylimidazolium hexafluorophosphate
decomposes in a vacuum in the temperature interval of T=(410 to 505) K according
to zero-order kinetics with the activation energy EA=68.0+/-2.8 kJ.mol-1.
PMID- 17034153
TI - Respective contributions of polar vs enthalpy effects in the
addition/fragmentation of mercaptobenzoxazole-derived thiyl radicals and
analogues to double bonds.
AB - The formation and the reactivity of three selected sulfur-centered radicals
formed from mercaptobenzoxazole, mercaptobenzimidazole, and mercaptobenzothiazole
toward four double bonds (methyl acrylate, acrylonitrile, vinyl ether, and vinyl
acetate) are investigated. The reversibility of the addition/fragmentation
reaction in these widely used photoinitiating systems of radical polymerization
was studied, for the first time, through the measurement of the corresponding
rate constants by time-resolved laser spectroscopy. The combination of these
results with quantum mechanical calculations clearly evidences that, contrary to
previous studies on other aryl thiyl radicals, the addition rate constants (ka)
are governed here by the polar effects associated with the very high
electrophilic character of these radicals. However, interestingly, the back
fragmentation reaction (k-a) is mainly influenced by the enthalpy effects as
supported by the relationship between the rate constants and the addition
reaction enthalpy DeltaHR. The addition and fragmentation rate constants
calculated from the transition state theory (TST) are in satisfactory agreement
with the experimental ones. Therefore, molecular orbital (MO) calculations
offered new opportunities for a better understanding of the sulfur-centered
radical reactivity.
PMID- 17034154
TI - Activation of electron-transfer reduction of oxygen by hydrogen bond formation of
superoxide anion with ammonium ion.
AB - A hydrogen bond formed between the superoxide anion and the ammonium ion (NH4+)
accelerates electron transfer from the C60 radical anion to oxygen significantly,
whereas the tetra-n-butylammonium ion has no ability to form a hydrogen bond with
the superoxidie anion, exhibiting no acceleration of the electron-transfer
reduction of oxygen. The second-order rate constant of electron transfer from
C60*- to O2 increases linearly with increasing concentration of NH4+. This
indicates that O2*- produced in the electron transfer from C60 to O2 is
stabilized by 1:1 complex formation between O2*- and NH4+. The 1:1 complex formed
between O2*- and NH4+ was detected by ESR. The binding of O2*- with NH4+ results
in a positive shift of the reduction potential of O2 with increasing
concentration of NH4+, leading to the acceleration of electron transfer from C60*
to O2.
PMID- 17034155
TI - Vibrational spectra and structures of H2O-NO, HDO-NO, and D2O-NO complexes. An IR
matrix isolation and DFT study.
AB - The IR spectra of H2O+NO, HDO+NO, and D2O+NO, isolated in solid neon at low
temperature have been investigated. Concentration effects and detailed
vibrational analysis of deuterated and partially deuterated species allowed
identification of three 1:1 HDO-NO species, two 1:1 D2O-NO species, and only one
1:1 H2O-NO complex. From comparison between the experimental spectra and the
results of DFT calculations, it appeared that two different types of weakly bound
complexes between water and nitric oxide can be formed in a neon matrix. The
first species is a 1:1 complex where bonding occurs between water hydrogen and
nitric oxide nitrogen, in which OH-N and OD-N intermolecular bonds are engaged.
For this complex only DOD-NO, HOD-NO, and DOH-NO isotopic species have been
experimentally detected and no IR bands of HOH-NO were observed. This result
could be explained by the fact that the dissociation energy of HOH-NO is lower
than those of DOD-NO, HOD-NO and DOH-NO. For the second detected 1:1 H2O-NO
complex and its isotopic variants, the H2O-NO potential surface was explored
systematically at the B3LYP level, but no stable species corresponding to the
complex could be calculated. The structure of the second observed 1:1 H2O-NO
complex results from columbic attractions between water and nitric oxide and
could be stabilized only in matrix, probably by interaction between NO, water and
(Ne)n.
PMID- 17034156
TI - Generation of gas-phase VO2+, VOOH+, and VO2+-nitrile complex ions by
electrospray ionization and collision-induced dissociation.
AB - Cationic metal species normally function as Lewis acids, accepting electron
density from bound electron-donating ligands, but they can be induced to function
as electron donors relative to dioxygen by careful control of the oxidation state
and ligand field. In this study, cationic vanadium(IV) oxohydroxy complexes were
induced to function as Lewis bases, as demonstrated by addition of O2 to an
undercoordinated metal center. Gas-phase complex ions containing the vanadyl
(VO2+), vanadyl hydroxide (VOOH+), or vanadium(V) dioxo (VO2+) cation and nitrile
(acetonitrile, propionitrile, butyronitrile, or benzonitrile) ligands were
generated by electrospray ionization (ESI) for study by multiple-stage tandem
mass spectrometry. The principal species generated by ESI were complexes with the
formula [VO(L)n]2+, where L represents the respective nitrile ligands and n=4 and
5. Collision-induced dissociation (CID) of [VO(L)5]2+ eliminated a single nitrile
ligand to produce [VO(L)4]2+. Two distinct fragmentation pathways were observed
for the subsequent dissociation of [VO(L)4]2+. The first involved the elimination
of a second nitrile ligand to generate [VO(L)3]2+, which then added neutral H2O
via an association reaction that occurred for all undercoordinated vanadium
complexes. The second [UO(L)4]2+ fragmentation pathway led instead to the
formation of [VOOH(L)2]+ through collisions with gas-phase H2O and concomitant
losses of L and [L+H]+. CID of [VOOH(L)2]+ caused the elimination of a single
nitrile ligand to generate [VOOH(L)]+, which rapidly added O2 (in addition to
H2O) by a gas-phase association reaction. CID of [VONO3(L)2]+, generated from
spray solutions created by mixing VOSO4 and Ba(NO3)2 (and precipitation of
BaSO4), caused elimination of NO2 to produce [VO2(L)2]+. CID of [VO2(L)2]+
produced elimination of a single nitrile ligand to form [VO2(L)]+, a V(V)
analogue to the O2-reactive V(IV) species [VOOH(L)]+; however, this V(V) complex
was unreactive with O2, which indicates the requirement for an unpaired electron
in the metal valence shell for O2 addition. In general, the [VO2(L)2]+ species
required higher collisions energies to liberate the nitrile ligand, suggesting
that they are more strongly bound than the [VOOH(L)2]+ counterparts.
PMID- 17034157
TI - Direct dynamics study on the reaction of N2H4 with F atom: a hydrogen abstraction
reaction?
AB - We present a systematic direct ab initio dynamics investigation of the reaction
between N2H4 and F atom, which is predicted to have three possible reaction
channels. The structures and frequencies at the stationary points and the points
along the minimum energy paths (MEPs) of all reaction channels were calculated at
the UB3LYP/6-31+G(d,p) level of theory. Energetic information of stationary
points and the points along the MEPs was further refined by means of the
CCSD(T)/aug-cc-pVTZ method. The calculated results revealed that the first two
primary channels (N2H4+F-->N2H3+HF) are equivalent and occur synchronously via
the formation of a pre-reaction complex with Cs symmetry rather than via the
direct H abstraction. The pre-reaction complex then evolves into a hydrogen
bonding intermediate through a transition state with nearly no barrier and a high
exothermicity, which finally makes the intermediate further decompose into N2H3
and HF. Another reaction channel of minor role (N2H4+F-->NH2F+NH2) was also found
during the calculations, which has the same Cs pre-reaction complex but forms
NH2F and NH2 via another transition state with high-energy barrier and low
exothermicity. The rate constants of these channels were calculated using the
improved canonical variational transition state theory with the small-curvature
tunneling correction (ICVT/SCT) method. The three-parameter ICVT/SCT rate
constant expressions of k(ICVT/SCT) at the CCSD(T)/aug-cc-pVTZ//UB3LYP/6
31+G(d,p) level of theory within 220-3000 K were fitted as (7.64x10(-9))T (-0.87)
exp(1180/T) cm3 mole-1 s-1 for N2H4+F-->N2H3+HF and 1.45x10(-12)(T/298)(2.17)
exp(-1710/T) cm3 mole-1 s-1 for N2H4+F-->NH2F+NH2.
PMID- 17034158
TI - Absorption cross sections of formaldehyde at wavelengths from 300 to 340 nm at
294 and 245 K.
AB - Absorption cross sections for the A1A2-X1A1 electronic transition of formaldehyde
have been measured by ultraviolet (UV) laser absorption spectroscopy in the
tropospherically significant wavelength range 300-340 nm, over which HCHO is
photochemically active. Absorption cross sections are reported at two
temperatures, 294 and 245 K and at a spectral resolution of 0.0035 nm (0.35 cm
1). At this resolution, greater peak absorption cross sections are obtained for
many of the sharp spectral features than were previously reported. To simulate
atmospheric conditions in the troposphere, the effects of adding a pressure of
nitrogen of up to 500 Torr and of reduced sample temperature were investigated.
The overall magnitudes of peak absorption cross sections are largely unaffected
by the added pressure of nitrogen, but a modest degree of pressure broadening
(0.2-0.3 cm-1 atm-1) is evident in the line shapes. Computer simulations of
spectra have been optimized by comparison with wavelength-dependent formaldehyde
absorption cross sections for each major vibronic band in the chosen wavelength
range. Experimental and computer simulated spectra at 294 and 245 K are compared
to test the reliability of the computer simulations for quantification of the
effects of temperature on absorption cross sections. All experimental absorption
cross section data and tables of input parameters for spectral simulations are
available as Supporting Information.
PMID- 17034159
TI - Diffusion kinetics for methanol in polycrystalline ice.
AB - Quantitative analyses of the isothermal desorption kinetics from methanol-doped
H2O films on Pt(111) reveal that transport kinetics for CH3OH in polycrystalline
ice are much slower than previously reported. They also indicate that MeOH
displays first-order desorption kinetics with respect to its instantaneous
surface concentration below 0.1 mole fraction in ice. These observations allow
isothermal desorption rate measurements to be interpreted in terms of a depth
profiling analysis providing one-dimensional concentration depth profiles from
methanol-doped polycrystalline ice films. Using a straightforward approach to
inhibit ice sublimation, transport properties are extracted from the evolution of
concentration depth profiles obtained after thermal annealing of binary ice films
at high temperature. Heterodiffusion coefficients for methanol in polycrystalline
(cubic) ice Ic films are reported for temperatures between 145 and 195 K and for
concentrations below 10(-3) mole fraction. Finally, diffusion kinetics for
methanol in ice are shown to display a very strong concentration dependence that
may contribute, in addition to variations in laboratory samples microstructure,
to the disagreements reported in the literature regarding the transport
properties of ice.
PMID- 17034160
TI - Estimation of electronic coupling for intermolecular electron transfer from cross
reaction data.
AB - Sixty-five electron-transfer reactions including 27 new 0, +1 couples have been
added to our data set of cross-reactions between 0 and +1 couples, bringing it to
206 reactions involving 72 couples that have been studied by stopped-flow
kinetics in acetonitrile containing supporting electrolyte at 25 degrees C,
formal potentials determined by cyclic voltammetry, and analyzed using Marcus
cross-rate theory. Perhaps surprisingly, a least-squares analysis demonstrates
that intrinsic rate constants exist that predict the cross-rate constants to
within a factor of 2 of the observed ones for 93% of the reactions studied, and
only three of the reactions have a cross-rate constant that lies outside of the
factor of 3, that corresponds to a factor of 10 uncertainty in the rate constant
for an unknown couple. Many triarylamines, which have very high intrinsic
reactivity, are included among the newly studied couples. The enthalpy
contribution to the Marcus reorganization energy, lambda'v, has been calculated
for 46 of the couples studied, at the (U)B3LYP/6-31+G (or for the larger and
lower barrier compounds, at the less time-consuming (U)B3LYP/6-31G) level. In
combination with a modified Levich and Dogodnadze treatment that assumes that the
rate constant is proportional to (KeHab2/lambda1/2) exp[-DeltaG/RT], this allows
estimation of the electronic coupling (Hab) at the transition state for
intermolecular electron transfer, (more properly H'ab, the product of the square
root of the encounter complex formation constant times Hab) for these couples.
Although the principal factor affecting intermolecular electron-transfer rate
constants is clearly lambda, H'ab effects are easily detectable, and the dynamic
range in our estimates of them is over a factor of 600.
PMID- 17034161
TI - Decomposition and isomerization of 1,2-benzisoxazole: single-pulse shock-tube
experiments, quantum chemical and transition-state theory calculations.
AB - Isomerization and decomposition of 1,2-benzisoxazole were studied behind
reflected shock waves in a pressurized driver, single-pulse shock tube. It
isomerizes to o-hydroxybenzonitrile, and no fragmentation is observed up to a
temperature where the isomerization is almost complete (approximately 1040 K at 2
ms reaction time). The isomerization experiments in this investigation covered
the temperature range 900-1040 K. The lack of fragmentation is in complete
contrast to the thermal behavior of isoxazole, where no isomerization was
observed and the main decomposition products over the same temperature range were
carbon monoxide and acetonitrile. In a series of experiments covering the
temperature range 1190-1350 K, a plethora of fragmentation products appear in the
post shock samples of 1,2-benzisoxazole. The product distribution is exactly the
same regardless of whether the starting material is 1,2-benzisoxazole or o
hydroxybenzonitrile, indicating that over this temperature range the 1,2
benzisoxazole has completely isomerized to o-hydroxybenzonitrile prior to
fragmentation. Two potential energy surfaces that lead to the isomerization were
evaluated by quantum chemical calculations. One surface with one intermediate and
two transition states has a high barrier and does not contribute to the process.
The second surface is more complex. It has three intermediates and four
transition states, but it has a lower overall barrier and yields the
isomerization product o-hydroxybenzonitrile at a much higher rate. The
unimolecular isomerization rate constants kinfinity at a number of temperatures
in the range of 900-1040 K were calculated from the potential energy surface
using transition-state theory and then expressed in an Arrhenius form. The value
obtained is kfirst=4.15x10(14) exp(-51.7x10(3)/RT) s-1, where R is expressed in
units of cal/(K mol). The calculated value is somewhat higher than the one
obtained from the experimental results. When it is expressed in terms of energy
difference it corresponds of ca. 2 kcal/mol.
PMID- 17034162
TI - Proton transfers induced by lead(II) in a uracil nucleobase: a study based on
quantum chemistry calculations.
AB - Within the context of metal biotoxicity, electrospray ionization mass
spectrometry experiments (ESIMS) have recently been performed by us on the
pyrimidine nucleobases (B) uracil and thymine complexed with lead(II) [Int. J.
Mass. Spectrom. 2005, 243, 279]. Among the ions detected, [Pb(B)-H]+ complexes,
where the base has been deprotonated, have been identified as producing intense
signals. In the same study, quantum calculations based on density functional
theory (DFT) have assessed the complexation sites and energies of [Pb(B)-H]+
ions. The present DFT investigations aim at giving an understanding on the
energetics and mechanisms associated with uracil's loss of a proton. We
specifically assess and quantify the role of lead binding in this process. For
that purpose, intra- and intermolecular proton transfers have been considered. We
have found that uracil (U) 1,3-tautomerization can be exergonic when uracil is
complexed with Pb2+, in opposition to the situation without lead. The
corresponding intramolecular processes were nonetheless found to occur at
geological time scales. In contrast, the addition of a second body to [Pb(U)]2+
complexes, namely OH- or H2O (as found in the initial water droplet of ESIMS
experiments), gives exergonic and fast uracil 1,3-proton transfers. Finally, we
have shown that intermolecular proton transfers in uracil-H2O, uracil-OH-, or
uracil-uracil complexes are able to explain the experimentally detected [Pb(U)
H]+ ions.
PMID- 17034163
TI - Molecular motion in crystalline naphthalene: analysis of multi-temperature X-ray
and neutron diffraction data.
AB - Single crystals of h8-naphthalene have been examined by both X-ray and neutron
diffraction over a range of temperatures from 5 to 295 K. The aim of this case
study was to measure the anisotropic displacement parameters (ADPs) of carbons
and hydrogens and to interpret them using the model of thermal motion proposed by
Burgi and Capelli (Acta Cryst. 2000, A56, 403). The traditional rigid-body
analysis expresses the low-frequency motions in terms of molecular translations
and librations only, whereas the Burgi-Capelli treatment also includes the high
frequency internal modes. We show that a considerable improvement occurs by
representing the internal modes by a single second-rank tensor and that a further
improvement follows by including a Gruneisen parameter to account for volume
thermal expansion. By applying the treatment to multi-temperature diffraction
data, there is a considerable reduction in the ratio of number of adjustable
parameters/number of independent observations.
PMID- 17034164
TI - Solvent effects on the photodissociation of formic acid: a theoretical study.
AB - Photodissociation of aqueous formic acid has been investigated with the CASSCF,
DFT, and MR-CI methods. Solvent effects are considered as a combination of the
hydrogen-bonding interaction from explicit H2O molecules and the effects from the
bulk surrounding H2O molecules using the polarizable continuum model. It is found
that the hydrogen-bonding effect from the explicit water in the complex is the
major factor to influence properties of aqueous formic acid, while the bulk
surrounding H2O molecules has a noticeable influence on the structures of the
complex. The direct C-O bond fission along the S1 pathway is predicted to be an
important channel upon photolysis of aqueous formic acid at 200 nm, which is
consistent with experimental observation that aqueous formic acid dissociates
predominantly into fragments of HCO and OH. The existence of a dark channel upon
photolysis of aqueous formic acid at 200 nm is assigned as fast relaxation from
the S1 Franck-Condon geometry to the T1/S1 intersection and subsequent S1-->T1
intersystem crossing process. S1-->S0 internal conversion followed by molecular
elimination to CO+H2O is the most probable primary process for formation of
carbon monoxide, which was observed with considerable yield upon photolysis of
aqueous formic acid at 253.7 nm.
PMID- 17034165
TI - Structure and stability of networked metallofullerenes of the transition metals.
AB - A DFT investigation of substitutionally doped fullerenes MC59 of second- and
third-row transition metals shows that their stability increases toward the right
hand side of the d-block. Whereas the structural deviation from that of C60
depends on the size of the metal atom, stability is governed by electronic
properties of the transition metal atom. A range of MC59 compounds of group 6-8
metals are predicted to have sufficient stability for experimental observation.
PMID- 17034166
TI - Structure, bonding, and lowest energy transitions in unsymmetrical squaraines: a
computational study.
AB - Natural resonance theory (NRT) and natural bond orbital (NBO) analysis have been
carried out on a simple symmetrical and an unsymmetrical substituted squaraine
with a view of understanding the structure of the latter type of squaraines. It
is found that there are some fundamental differences in the structure and bonding
between these two types of squaraines particularly in the resonance weights and
delocalization energies. These differences are expected to reflect in the low
energy transitions and charge transfer in these squaraines. To investigate this,
the nature of the lowest energy transitions occurring on excitation in
unsymmetrical squaraines has been studied using high-level symmetry adapted
cluster-configuration interaction method (SAC/SAC-CI) and compared with reported
experimental observations. In general the agreement with the experimental data is
very good. The transition dipole moment always lies on the pi-backbone and is
quite large in magnitude. The ground state dipole moment in some cases does not
change in the excited state upon excitation while in some other cases there is a
large reduction/enhancement in the magnitude indicative of some charge
rearrangement in this direction. Inclusion of the solvent using the IEFPCM model,
a slightly better agreement with the experiment is found in some cases. Studies
are carried out with a different basis set and it is found that the change in
basis set has very little effect on the transition energies. In the case of weak
side donor groups attached to the central ring the larger charge transfer to the
central acceptor ring in general takes place from the O- atoms of the squarylium
moiety while in the case of strong donors the charge transfer from the O- atoms
to the central rings drop down. We have not observed any correlation between the
charge transfer in the excited state to the central ring from the side donor
groups and the lowest energy excitation in the molecules. Reduction of the HOMO
LUMO gap (an indication of increase of the diradicaloid character) always leads
to a bathochromic shift.
PMID- 17034167
TI - Preferential site of attack on fullerene cations: frontier orbitals and rate
coefficients.
AB - An analysis of reaction efficiency is presented for reactions of carbonaceous
ions and molecules. Our results show that the combination of experimental rate
coefficient measurements and computations of the condensed Fukui functions of
frontier molecular orbitals and pyramidal angles of pi orbitals is very useful
for elucidating the reactive sites on fullerene carbon clusters in the gas phase.
PMID- 17034168
TI - A new perspective in the Lewis acid catalyzed ring opening of epoxides.
Theoretical study of some complexes of methanol, acetic acid, dimethyl ether,
diethyl ether, and ethylene oxide with boron trifluoride.
AB - Several 1:1, 1:2, and 2:2 complexes between BF3 and CH3OH (Met), CH3COOH (AcA),
(CH3)2O (DME), (CH3CH2)2O (DEE), and (CH2)2O (EOX) have been studied using ab
initio (MP2) and density functional theory (DFT) (PBE, B3LYP) methods and the 6
311++G(3df,2pd) basis set. Geometrical structures and vibrational frequencies are
reported, in most cases, for the first time. A detailed comparison of the
vibrational frequencies for the O...BF3 vibrational modes, as well as for the
nu(OH) band in the methanol and acetic acid complexes with BF3, is performed, and
the theoretical frequency shifts are compared with the available experimental
information. Thermochemical properties are calculated by employing counterpoise
correction to alleviate the basis set superposition error. The DFT enthalpy of
complexation of the 1:1 complexes results in the order of stability
(AcA)2>AcA:BF3>DEE:BF3>DME:BF3>Met:BF3>EOX:BF3>(Met)2; in contrast, MP2 shows the
noticeable difference that the AcA:BF3 complex is much less stable (similar to
Met:BF3). The order of stability shows that, even though acetic acid prefers
dimerization to complexation with BF3, the case is exactly the opposite for
methanol. In both cases, the interaction of BF3 with the dimer gives rise to very
stable trimers. However, in contrast to the interaction of BF3 with the methanol
dimer being stronger than that with the monomer, the interaction of BF3 with the
acetic acid dimer is weaker than that with the monomer. The relative strength of
the complexes, discussed in the context of BF3-catalyzed ring opening of
epoxides, suggests that the effect of the catalyst in a nonprotogenic solvent
should be more properly ascribed to activation of the nucleophile instead of
activation of the epoxide.
PMID- 17034169
TI - On the electronic origin of strain energy: QTAIM study of perfluorocycloalkanes.
AB - The strain energies (SE) of the five smallest perfluorocycloalkanes (c-CnF2n;
n=3, 4, 5, 6, and 7) were calculated by means of several homodesmotic processes
using B3LYP/6-31++G(d,p) optimized molecular energies. These values were compared
with the energy difference between the linear and cyclic CF2 groups calculated by
means of the quantum theory of atoms in molecules (QTAIM) applied on charge
densities obtained at the same computational level. The differences between the
values computed with both methods vary from 255 (n=3) to 629 (n=7) kJ mol-1.
These differences arise because QTAIM-computed SE contain the energy involved in
opening the ring to give rise to nearly transferable central CF2 fragments of
linear perfluoroalkanes, whereas homodesmotic energies contain energy terms
corresponding to transformation of nontransferable linear CF2 fragments and a
ring-opening energy, which depending on the process, transforms CF2 cyclic
compounds into nearly transferable or nontransferable linear CF2 groups.
PMID- 17034170
TI - Theoretical study of hydrogen bonding interaction in nitroxyl (HNO) dimer:
interrelationship of the two N-H...O blue-shifting hydrogen bonds.
AB - The hydrogen bonding interactions of the HNO dimer have been investigated using
ab initio molecular orbital and density functional theory (DFT) with the 6
311++G(2d,2p) basis set. The natural bond orbital (NBO) analysis and atom in
molecules (AIM) theory were applied to understand the nature of the interactions.
The interrelationship between one N-H...O hydrogen bond and the other N-H...O
hydrogen bond has been established by performing partial optimizations. The dimer
is stabilized by the N-H...O hydrogen bonding interactions, which lead to the
contractions of N-H bonds as well as the characteristic blue-shifts of the
stretching vibrational frequencies nu(N-H). The NBO analysis shows that both
rehybridization and electron density redistribution contribute to the large blue
shifts of the N-H stretching frequencies. A quantitative correlations of the
intermolecular distance H...O (r(H...O)) with the parameters: rho at bond
critical points (BCPs), s-characters of N atoms in N-H bonds, electron densities
in the sigma*(N-H), the blue-shift degrees of nu(N-H) are presented. The
relationship between the difference of rho (|Deltarho|) for the one hydrogen bond
compared with the other one and the difference of interaction energy (DeltaE) are
also illustrated. It indicates that for r(H...O) ranging from 2.05 to 2.3528 A,
with increasing r(H...O), there is the descending tendency for one rho(H...O) and
the ascending tendency for the other rho(H...O). r(H...O) ranging from 2.3528 to
2.85 A, there are descending tendencies for the two rho(H...O) with increasing
r(H...O). On the potential energy surface of the dimer, the smaller the
difference between one rho(H...O) and the other rho(H...O) is, the more stable
the structure is. As r(H...O) increases, the blue-shift degrees of nu(N-H)
decrease. The cooperative descending tendencies in s-characters of two N atoms
with increasing r(H...O) contribute to the decreases in blue-shift degrees of
nu(N-H). Ranging from 2.05 to 2.55 A, the increase of the electron density in one
sigma*(N-H) with elongating r(H...O) weakens the blue-shift degrees of nu(N-H),
simultaneously, the decrease of the electron density in the other sigma*(N-H)
with elongating r(H...O) strengthens the blue-shift degrees of nu(N-H). Ranging
from 2.55 to 2.85 A, the cooperative ascending tendencies of the electron
densities in two sigma*(N-H) with increasing r(H...O) contribute to the decreases
in blue-shift degrees of nu(N-H).
PMID- 17034171
TI - The singlet-triplet gap in trimethylenmethane and the ring-opening of
methylenecyclopropane: a multireference Brillouin-Wigner coupled cluster study.
AB - We performed an ab initio study of the singlet-triplet gap in trimethylenmethane
(TMM) and of the ring-opening of methylenecyclopropane by the multireference BWCC
method. Since the singlet states of TMM and intermediates between TMM and
methylenecyclopropane have a strong multiconfigurational character, it is
necessary to use a multireference method. The cc-pVDZ and cc-pVTZ basis sets were
used. We compared our results with experiments, where available, and with
previous calculations performed by MCSCF and spin-flip coupled-cluster-type
methods.
PMID- 17034172
TI - Experimental and molecular dynamics studies of dysprosium(III) salt solutions for
a better representation of the microscopic features used within the binding mean
spherical approximation theory.
AB - This work is aimed at a predictive description of the thermodynamic properties of
actinide(III) salt solutions at high concentration and 25 degrees C. A new
solution of the binding mean spherical approximation (BIMSA) theory, based on the
Wertheim formalism, for taking into account 1:1 and also 1:2 complex formation,
is used to reproduce, from a simple procedure, experimental osmotic coefficient
variation with concentration for three binary salt solutions of the same
lanthanide(III) cation: dysprosium(III) perchlorate, nitrate, and chloride. The
relevance of the fitted parameters is discussed, and their values are compared
with available literature values. UV-vis/near-IR, time-resolved laser-induced
fluorescence spectroscopy experiments, and molecular dynamics (MD) calculations
were conducted for dilute to concentrated solutions (ca. 3 mol.kg-1) for a study
of the microscopic behavior of DyCl3 binary solutions. Coupling MD calculations
and extended X-ray absorption fine structure led to the determination of reliable
distances. The MD results were used for a discussion of the parameters used in
the BIMSA.
PMID- 17034173
TI - Transient oxygen clathrate-like hydrate and water networks induced by magnetic
fields.
AB - Recently, careful experiments of oxygen-dissolved pure water treated by high
magnetic fields showed indirectly the existence of magnetic field-affecting water
(MFA water), which brought about a decrease in the contact angle of water on
metals, an increase in the electrolytic potential of water, inhibition of metal
corrosion, and changes in the crystal structure of calcium carbonate due to
magnetic treatment. Here we report the infrared and Raman spectroscopic evidence
indicating quasi-stable structures in the MFA water; oxygen clathrate-like
hydrate and developed water networks, which were induced by magnetic interactions
while a vacuum-distilled water, followed by oxygen exposure, crossed a steady
magnetic field. The mechanism of MFA water formation and survival under thermal
fluctuation is a challenging problem for the science community.
PMID- 17034174
TI - Comparison of intra- vs intermolecular long-range electron transfer in crystals
of ruthenium-modified azurin.
AB - Selective metal-ion incorporation and ligand substitution are employed to control
whether electrons tunnel over intra- or intermolecular separations in crystals of
P. aeruginosa azurin modified with Ru-polypyridine complexes. Cu(1+)-to-Ru3+
electron transfer (ET) across a specific protein-protein interface in the crystal
lattice has a time constant 5-10 times longer than ET between the same donor and
acceptor within a single protein (tauET = 5 vs 0.5-1.0 micros). Slower
intermolecular ET agrees well with a longer distance between redox centers across
the inter-protein (18.9 A) compared to the intra-protein separation (17.0 A) and
indicates that the closest donor/acceptor pair dominates crystal ET. Lowering the
crystal pH accelerates inter-protein ET (tauET = 1.0 micros) but not intra
protein ET. Faster inter-protein ET likely results from a pH-induced peptide bond
flip that perturbs hydrogen bonding in the path between Ru and Cu centers on
adjacent molecules.
PMID- 17034175
TI - Assembly of linear clusters of iodobenzene dimers on Cu(110).
AB - Low-temperature STM observations of the low-coverage chemisorption behavior of
iodobenzene on Cu(110) are presented at two annealing temperatures. When a random
distribution of isolated iodobenzene molecules deposited at T < 100 K is annealed
to approximately 170 K, the undissociated molecules assemble into chainlike
clusters composed of identical subunits. An STM tip-induced dissociation reaction
is used to determine that the individual units in the chains are composed of
pairs of iodobenzene molecules. A model is proposed in which iodine atoms on each
member of the pair are directed toward one another. The driving force for the
formation of such clusters is suggested to be the dispersion interactions between
the polarizable iodobenzene molecules.
PMID- 17034176
TI - Acoustic multibubble cavitation in water: A new aspect of the effect of a rare
gas atmosphere on bubble temperature and its relevance to sonochemistry.
AB - Acoustic cavitation generates transient microbubbles with extremely high
temperatures and high pressures, which can provide unique reaction routes. The
maximum bubble temperature attained is widely known to be dependent on the
polytropic index and thermal conductivity of the dissolved gas. Here, we show for
the first time experimental evidence that the bubble temperature induced by a
high frequency ultrasound is almost the same among different rare gases and the
chemical efficiency is in proportion to the gas solubility of rare gases, which
would be closely related to the number of active bubbles.
PMID- 17034178
TI - Spontaneous formation of triptycene supramolecules on surfaces.
AB - In the limit of weak molecular interaction with an inorganic surface, noncovalent
interactions between molecules dominate the nucleation and thin-film growth.
Here, we report on the formation of three-dimensional triptycene clusters with a
particularly stable structure. Once formed at the early stage of molecular
adsorption, the clusters are stable for all temperatures until desorption.
Furthermore, the clusters diffuse and nucleate as individual entities, therefore
constituting building blocks for the later thin-film formation. High resolution
scanning tunneling microscopy images indicate that the cluster is stabilized by C
H-pi interactions. The formation of such molecular structures at a surface is
possible because the three-dimensional structure of the triptycene molecule leads
to a very weak and mobile adsorption state. These results show that it is
possible to investigate complex pathways in the formation of three-dimensional
supramolecules at surfaces using a scanning tunneling microscope.
PMID- 17034177
TI - trans-cis Photoisomerization of a photoactive yellow protein model chromophore in
crystalline phase.
AB - We have studied the photoinduced trans/cis isomerization of the protonated form
of p-hydroxycinnamic thiophenyl ester, a model chromophore of the photoactive
yellow protein (PYP), in crystalline phase, by both fluorescence and infrared
spectroscopies. The conversion from trans to cis configuration is revealed by a
shift of the fluorescence peak and by inspection of the infrared maker bands. The
crystal packing apparently stabilizes the cis photoproduct, suggesting different
environmental effects from the solvent molecules for this model chromophore in
liquid solutions or from the amino acid residues for the PYP chromophore.
PMID- 17034179
TI - When does the Michaelis-Menten equation hold for fluctuating enzymes?
AB - Enzymes are dynamic entities: both their conformation and catalytic activity
fluctuate over time. When such fluctuations are relatively fast, it is not
surprising that the classical Michaelis-Menten (MM) relationship between the
steady-state enzymatic velocity and the substrate concentration still holds.
However, recent single-molecule experiments have shown that this is the case even
for an enzyme whose catalytic activity fluctuates on the 10(-4)-10 s range. The
purpose of this paper is to examine various scenarios in which slowly fluctuating
enzymes would still obey the MM relationship. Specifically, we consider (1) the
quasi-static condition (e.g., the conformational fluctuation of the enzyme
substrate complex is much slower than binding, catalysis, and the conformational
fluctuations of the free enzyme), (2) the quasi-equilibrium condition (when the
substrate dissociation is much faster than catalysis, irrespective of the time
scales or amplitudes of conformational fluctuations), and (3) the conformational
equilibrium condition (when the dissociation and catalytic rates depend on the
conformational coordinate in the same way). For each of these scenarios, the
physical meaning of the apparent Michaelis constant and catalytic rate constant
is provided. Finally, as an example, the theoretical analysis of a recent single
molecule enzyme assay is considered in light of the perspectives presented in
this paper.
PMID- 17034180
TI - Aromatic superclusters from all-metal aromatic and antiaromatic monomers, [Al4]2-
and [Al4]4-.
AB - Calculations on the structures of dimers of all-metal aromatic and anti-aromatic
molecules such as (Al4(2-)) and (Al4(4-)) reveal that, unlike their organic
counterparts such as benzene and cyclobutadiene which form pi-stacked complexes,
these molecules form new clusters with no reminiscence of the original units.
These clusters have a very large binding energy and can be further stabilized
through charge-balance by counterions and solvents.
PMID- 17034181
TI - Vertically aligned dense carbon nanotube growth with diameter control by block
copolymer micelle catalyst templates.
AB - We have grown a dense array of vertically aligned carbon nanotubes (CNTs) with a
controlled distribution of diameters by using block copolymer micelles to form
and pattern catalyst particles. The block copolymer poly(styrene-block-acrylic
acid) (PS16500-PAA4500) was dissolved in toluene to form micelles and then loaded
with FeCl3. The metal-loaded micelles were spin-coated on Si and then thermally
treated to remove the polymer. Using this process, we produced surfaces patterned
with iron oxide catalyst particles with particle densities ranging from 1400
microm(-2) to 3800 microm(-2) and a size distribution of (6.9 +/- 0.8) nm. CNT
growth by thermal chemical vapor deposition was then performed on these samples.
The low-density catalyst sample produced unaligned, low-density CNTs, whereas the
high-density catalyst sample produced vertically aligned, dense CNTs about 10
microm in length. Transmission electron microscopy revealed that the CNTs
typically had double and triple graphitic layers with normally distributed
diameters of (4.5 +/- 1.1) nm. For comparison, CNTs grown from the standard
approach of blanket Fe films had a wide distribution of diameters between 6 and
21 nm. This catalyst preparation approach dramatically sharpens the size
distribution of CNTs, compared to standard approaches, and provides a simple
means of controlling the areal density of CNTs.
PMID- 17034182
TI - Ultrafast vibrational spectroscopy of the flavin chromophore.
AB - Ultrafast time-resolved infrared (TRIR) spectra of flavin adenine dinucleotide
(FAD) and the anion of lumiflavin (Lf-) are described. Ground-state recovery and
excited-state decay of FAD reveal a common dominant ultrafast relaxation and a
minor slower component. The Lf- transient lacks a fast component. No intermediate
species are observed, suggesting that the quenching mechanism is internal
conversion promoted by interaction of the adenine and isoalloxazine rings in FAD.
Modes are assigned, and the potential for extension of the TRIR method to
photoactive proteins is discussed.
PMID- 17034183
TI - Photoinduced molecular transport in biological environments based on dipole
moment fluctuations.
AB - Consideration is given to the possibility of a molecule moving unidirectionally
in an electric field of a polar periodic substrate as a result of the
fluctuations of molecular dipole moment occurring on the photoexcitation of the
molecule. As estimated for such motion, molecules with sufficiently long
fluorescence and strongly differing dipole moments in the ground and excited
states can move with an average velocity of the same order as that typical of
protein motors such as kinesin. This effect results from the mutual compensation
of two opposite factors acting in dipole photomotors, namely, a lower energy of
interaction with the substrate relative to that for protein motors and a shorter
excited-state lifetime as compared with the duration of the hydrolytic splitting
of adenosinetriphosphate in protein motors.
PMID- 17034184
TI - Long-lived interfacial vibrations of water.
AB - We have observed long-lived OH-stretch (nu(OH)) excitations (v = 1) in water
during ultrafast laser ablation by a mid-infrared pulse tuned to the nu(OH)
absorption maximum. The spectrum of excitations is measured using incoherent anti
Stokes Raman spectroscopy. Relative to the equilibrium water spectrum, these
excitations evidence a narrowed (100 cm(-1) fwhm) and blue-shifted (3600 cm(-1)
peak) transition. The excited-state lifetime is T1 > 200 ps, compared to 0.2 ps
in bulk water. In the early stages of the ablation process, the water mean
density decreases rapidly, which breaks up the hydrogen bonding. The long-lived
species is attributed to nu(OH) excitations on water molecules associated with
interfaces, having broken hydrogen bonds which cannot be rapidly reformed as in
the liquid state.
PMID- 17034185
TI - Chemical functionalization of magnetic carbon-encapsulated nanoparticles based on
acid oxidation.
AB - Carbon-encapsulated nickel nanoparticles were used as the representative magnetic
carbon-encapsulated nanoparticles for chemical functionalization. After oxidation
with the mixed acid of H2SO4/HNO3 under a moderate ultrasonic bath, carboxylic
acid groups (-COOH) were effectively generated on the fullerene-like carbon
shells, which in turn were utilized to covalently link octadecylamine through an
amide reaction. The whole chemical process is well characterized by many methods
such as Fourier transform infrared spectroscopy, X-ray photoelectron
spectroscopy, thermogravimetry-differential scanning calorimetry, transmission
electron microscopy, and so on, and the self-consistent experimental results were
obtained. The results suggested that the magnetic nanoparticles could be well
protected, while their magnetic properties could be utilized to guide the
transfer of the grafted functional species on the particle surface. This provides
many possibilities for potential applications in chemical and biochemical fields.
PMID- 17034186
TI - A neutron scattering and nuclear magnetic resonance study of the structure of
GeO2-P2O5 glasses.
AB - Germanophosphate (GeO2-P2O5) glasses were studied with neutron diffraction,
phosphorus, and oxygen nuclear magnetic resonance, calorimetry, viscosity
measurements, and first-principles calculations. These data sets were combined to
propose a structural model of GeO2-P2O5 glasses, which includes tetrahedrally
coordinated phosphorus, formation of octahedrally coordinated germanium as P2O5
content increases, an absence of trigonally coordinated oxygen, and hence an
absence of rutile-like GeO2 domains. The structural model was then used to
propose explanations for both the observed composition dependence of the glass
transition temperature and the fragility of the GeO2-P2O5 liquids.
PMID- 17034187
TI - Unconventional zigzag indium phosphide single-crystalline and twinned nanowires.
AB - Unconventional zigzag indium phosphide (InP) single-crystalline and twinned
nanowires were produced via thermal evaporation of indium phosphide in the
presence of zinc selenide. The structure and morphology of the as-synthesized
products were characterized by X-ray diffraction, scanning electron microscopy,
and transmission electron microscopy. Studies found that two type of nanowires
exist in the products, namely, the periodic-rhombus-decorated single-crystalline
InP (type I) nanowires and jagged twinned InP (type II) nanowires. Both of them
have preferential 111 growth directions. The optical properties were also
investigated at room temperature, and they show that the nanowires display a
strong emission at approximately 750 nm, which is quite different from that
observed in all previous reports related to the InP nanostructures.
PMID- 17034188
TI - Combining small angle neutron scattering (SANS) and fluorescence correlation
spectroscopy (FCS) measurements to relate diffusion in agarose gels to structure.
AB - Small angle neutron scattering (SANS) and fluorescence correlation spectroscopy
(FCS) measurements were carried out on agarose hydrogels to link their
microscopic structure to the diffusivity of solutes at different scales. SANS
allowed for the determination of the distribution of void volumes within the
gels. They were shown to be compatible with a random network of cylindrical
fibers as described by the Ogston model. FCS measured solute diffusivity in
spaces similar in size to the void volumes, and thus, the results reflected the
gel heterogeneity. Solute diffusivity was predicted by modeling the gel as
microscopic geometrical cells. Variations in the diffusivity of solutes of
different sizes could be predicted from the structural parameters of the gel
using theory, taking into account obstruction by cylindrical cells and solute
hydrodynamics. Prediction of the FCS autocorrelation functions for solutes from a
cell model demonstrated a lack of sensitivity of this technique for
multicomponent analysis.
PMID- 17034189
TI - Dynamics of alkyl ammonium intercalants within organically modified
montmorillonite: Dielectric relaxation and ionic conductivity.
AB - The low-frequency (0.01 Hz-10 MHz) dynamic characteristics of alkyl quaternary
ammonium exchanged montmorillonite (SC20A) were investigated to determine the
correlation between temperature-dependent changes in the interlayer structure and
collective mobility of the surfactant. From 25 to 165 degrees C, SC20A exhibits
two interlayer transitions, one ascribed to the melting of the intercalated alkyl
chains of the surfactant (20-40 degrees C) and another associated with an abrupt
decrease in the interlayer's coefficient of thermal expansion (100 degrees C).
For this temperature range, the excess surfactant and residual electrolytes
present in commercially manufactured SC20A enhance the direct current
conductivity and increase low-frequency space-charge polarization, which is
believed to occur across percolation paths established by the surfaces of the
SC20A crystallites. In contrast, a higher-frequency relaxation, which was less
sensitive to process history and impurity content, is ascribed to relaxation
within the interlayer at the surfactant-aluminosilicate interface electrostatic
couple. The temperature dependence of these dielectric relaxations indicated a
drastic increase in mobility as the interlayer organic phase transitions from
static and glasslike into molten and mobile. Overall, SC20A displayed features of
alternating current universality, including time-temperature superposition,
common in other types of disordered ion-conducting media. The presence of long
range transport and its sensitivity to low amounts of impurities imply that from
a dynamic perspective the local environment of the surfactants are substantially
diverse and a minority fraction, such as at the edge of the crystallite (gallery
and aluminosilicate layer), may dominate the lower-frequency dielectric response.
PMID- 17034190
TI - Structural, magnetic, and magnetoresistive properties of electrodeposited Ni5Zn21
alloy nanowires.
AB - Ni5Zn21 alloy nanowires were fabricated through template-assisted electrochemical
deposition method. The morphology and microstructures of as-deposited nanowires
were determined by field-emission scanning electron microscope (FE-SEM), X-ray
diffraction (XRD), high-resolution transmission electron microscope (HRTEM),
electron diffraction (ED), and electron probe microanalysis (EPMA). The accurate
composition was measured via induced coupling plasma atomic emission
spectroscopy. SEM results show that Ni5Zn21 nanowires are deposited in most of
the nanopores of the template, and they are continuous and dense throughout the
whole length. The XRD result demonstrates that the nanowires are mainly composed
of a cubic gamma phase Ni5Zn21 alloy, but there also exists a trace of Zn-rich
eta phase. HRTEM and ED reveal that the alloy nanowires are polycrystalline with
the crystallite size of several tens of nanometers. EPMA of a single nanowire
illustrates that there exist Ni-rich microzones in as-deposited nanowires.
Subsequent magnetic measurements of the array also confirmed the existence of
them. In addition, it can be further inferred that the shape of Ni-rich
microzones is probably barlike or disklike, from the anisotropy of zero field
cooling/field cooling (ZFC/FC) curves as well as the vortex magnetization
behavior of the Ni5Zn21 nanowire array. The low-temperature magnetoresistance of
the Ni5Zn21 nanowire array was also measured. Giant magnetoresistance instead of
anisotropic magnetoresistance is suggested to be responsible for contributing to
the magnetoresistance.
PMID- 17034191
TI - Evaluation of a new force field for describing the adsorption behavior of alkanes
in various pure silica zeolites.
AB - The recently proposed united atom force field by Dubbeldam et al. (Phys. Rev.
Lett. 2004, 93, 088302) for the adsorption of alkanes in MFI-type zeolites was
extended to other zeolites in this work. Its applicability to FER-type zeolites
was evaluated in detail, for which the Henry coefficients, the isosteric heat of
adsorption, the adsorption isotherms, as well as the locations of alkanes in the
FER-type zeolites were computed and compared to experimental values. The results
show that the new force field works well for FER zeolites. Furthermore, its
applicability to MWW-, MTW-, CFI-, LTA-, and STF-type zeolites was investigated,
and we found that the experimental isotherms could be accurately predicted except
for STF-type zeolites. This work shows that the new united atom force field
proposed by Dubbeldam et al. is applicable to most pure silica zeolites.
PMID- 17034192
TI - Porogen approach for the fabrication of plasma-polymerized nanoporous
polysiloxane films.
AB - Nanoporous polysiloxane films were fabricated by plasma polymerization of
hexamethyldisiloxane mixed with cyclohexane under different conditions. The pores
were generated through the elimination of carbonaceous aggregates (porogen) by
annealing at 600 degrees C. Results of spectroscopic ellipsometry, Fourier
transform infrared spectroscopy, and positron annihilation lifetime spectroscopy
suggest that not only film porosity but also average pore size depends on the
amount of the decomposable porogen. The pore size was controllable in a range
between 0.6 and 1.0 nm in radius by proper selection of the substrate temperature
and precursor composition.
PMID- 17034193
TI - Characterization of the metal-organic framework compound Cu3(benzene 1,3,5
tricarboxylate)2 by means of 129Xe nuclear magnetic and electron paramagnetic
resonance spectroscopy.
AB - 129Xe NMR measurements of adsorbed xenon are shown for the first time to be a
suitable tool to characterize the porosity and the properties of the metal
organic framework Cu3(BTC)2(H2O)3 (BTC = benzene 1,3,5-tricarboxylate). The NMR
experiments are performed at room temperature and over a wide range of xenon
pressure and on two different synthesized Cu3(BTC)2 samples. 129Xe NMR results
reveal that in dependence on the kind of the synthesis pathway either one or two
signals are observed which can be attributed to two kinds of fast exchange of
xenon atoms in two pores with different pore sizes. Coadsorption experiments of
xenon and ethylene demonstrate that the xenon atoms prefer to fill the greater
pores of the material because the smaller pores are occupied with residual
molecules from the synthesis procedure and additionally adsorbed ethylene.
Besides the NMR experiments a series of electron paramagnetic resonance (EPR)
measurements are performed to estimate the state of copper having a strong
influence on the chemical shift of the adsorbed xenon. The EPR experiments
demonstrate that spin exchange between the interconnected copper dimers is taking
place across the BTC linker molecules in the Cu3(BTC)2 framework.
PMID- 17034194
TI - Polymer-assisted growth of molybdenum oxide whiskers via a sonochemical process.
AB - Whiskers of molybdenum oxides with high aspect ratios were synthesized from
peroxomolybdate precursor solutions in the presence of small amounts of
poly(ethylene glycol) (PEG) via a sonochemical process at temperatures of 25-70
degrees C. Irradiation with ultrasound reduces the time needed for the growth of
micrometer-sized whiskers from weeks to a few hours. The simplicity of the
sonochemical approach also compares favorably to a hydrothermal/solvothermal
process. The morphology, crystal structure, and other characteristics of the
whiskers were characterized by scanning electron microscopy, transmission
electron microscopy, selective area electron diffraction, energy-dispersive X-ray
spectroscopy, wide-angle X-ray diffraction, Raman spectroscopy, thermogravimetric
analysis, differential scanning calorimetry, and the Brunauer-Emmett-Teller
method. The surface area of the calcified molybdenum oxide whiskers (55.4 m2/g)
was found to be much higher than those of molybdenum oxide nanofibers (35 m2/g)
or nanorods (13.4 m2/g) The growth rate of various crystal faces could be
postulated to be controlled by the binding of peroxomolybdate ions to pseudo
crown ether cavities formed by PEG. The reduction of molybdenum oxide to produce
mixed-valent oxides and their growth could also be controlled by the reducing
ability of PEG. The aspect ratio of the molybdenum oxide whiskers increased with
decreasing concentration in the initial peroxomolybdate precursor solution.
Whether the precursor solution species was H2Mo2O3(O2)4(H2O)2, H2MoO2(O2)2, or
MoO2(OH)(OOH), the peroxide group in all the species disproportionates to give
the final product MoO3 by a catalytic process. On the basis of experimental
evidence of the dual role of glycols, a mechanism for the growth of the
molybdenum oxide whiskers is proposed.
PMID- 17034195
TI - Photoelectrochemistry of conducting polymers modified with electron-acceptor
moieties.
AB - The photoelectrochemical behavior of two polymers of the polythiophene series
containing electron-acceptor groups in the main chain was studied and compared to
that of the nonmodified polymer, poly(2,2'-bithiophene), PBT. The acceptor groups
were 2,2'-bipyridine and biphenyl, which are electron-deficient as compared to
the bithiophene unit. All three polymers demonstrated a pronounced photovoltaic
effect, which for PBT was consistent with data reported earlier. The introduction
of the electron-acceptor moieties was found to significantly enhance the
magnitude of the steady-state photocurrent as well as to drastically alter the
dependencies of the photocurrent on the polymer film thickness and the external
bias. These observations indicated that the mechanism of photocurrent generation
in the modified polymers differs from that in nonmodified polymer and involves
the electron transfer to the electron-acceptor moieties in the polymer main
chain. The values of the external quantum efficiency were estimated in a liquid
cell arrangement to be 0.27 and 0.19% for modified and nonmodified polymers,
respectively.
PMID- 17034196
TI - Dendritic aggregation of oligothiophene during desorption of 2,5-diiodothiophene
multilayer and topography-induced alignment of oligothiophene nanofibers.
AB - The multilayer desorption behavior of 2,5-diidothiophene and the dendritic
aggregation of photochemical reaction products during the desorption of 2,5
diiodothiophene multilayers have been studied. Like many other aromatic
compounds, 2,5-diiodothiophene shows a multilayer desorption behavior different
from the typical zeroth-order kinetics, a metastable desorption peak growth at
approximately 220 K followed by a thick multilayer peak growth at approximately
235 K. Traditionally, these desorption behaviors have been attributed to the
formation of three-dimensional clusters. This paper provides the direct evidence
of this clustering process by producing nondesorbing photoreaction products in
the multilayer and by imaging their clusters after the multilayer desorption.
Oligothiophene species are produced via photochemical reactions of 2,5
diiodothiophene during the multilayer deposition at approximately 180 K in
ultrahigh vacuum (UHV). Upon heating the multilayer to room temperature, the
oligothiophene species forms into fibrous aggregates with a fractal dimension
varying from 1.37 to 1.81 depending on their surface concentration. Using a
topographical alteration of the substrate with a repeating pattern, these
oligothiophene fibers can be aligned to a certain direction. This may allow in
situ fabrication of aligned conjugated polymer fibers directly on a target
substrate.
PMID- 17034197
TI - Synthesis of large-pore micelle-templated silico-aluminas at different alumina
contents.
AB - The EPR spectra of radical surfactant probes embedded in cetyltrimethylammonium
bromide (CTAB) and trimethylbenzene (TMB) stable water emulsions (TMB/CTAB = 13)
were analyzed to provide information on the kinetics of formation of micelle
templated silicoaluminas (MTSA) at 343 K, obtained by means of silica and
alumina, solved in alkaline solutions, at different Si/Al ratios. Textural
(surface area, pore volume, pore size, surfactant content) and structural
characterization of both as-synthesized and calcined MTSA were performed by means
of nitrogen sorption isotherms, TEM, and chemical analysis. This analysis showed
that TMB worked as a swelling agent of the CTAB micelles, providing large-pore
homogeneous and stable MTSA at TMB/CTAB = 13 for Si/Al from infinity to 10. A
demixing of the emulsion occurs at Si/Al < 10: at Si/Al = 7, a double wide-and
narrow pore structure was formed; then, at Si/Al = 5, an amorphous material was
obtained. At Si/Al > or = 10, the computer-aided analysis of the EPR spectra as a
function of the synthesis time indicated the distribution of the probes in two
different environments: "micellar" probes inserted in the surfactant aggregates,
whose mobility decreases over the synthesis time, thus reporting on the
progressive modification of the surfactant aggregates structure and the solid
condensation, and "interacting" probes due to probe-surfactant heads
electrostatically interacting with the charged surface sites induced by alumina
incorporation in the silica network. This last fraction increases its relative
amount over the synthesis time, informing about the condensation and
structuration of the MTSA. Without alumina, the "interacting" component is absent
in the EPR spectra because TMB preferentially interacts with the surfactant
headgroups by cation-pi interactions, thus preventing the interactions of these
headgroups with silanols. When alumina is added, the negatively charged
silicoaluminate at the surface promotes the interaction of the ammonium
headgroups with the surface, and some Na+ cations also interact with TMB by
cation-pi interaction and contribute to decreasing the interaction of the
headgroups with TMB. Therefore, increasing alumina contents promote electrostatic
interactions between the positively charged surfactant heads and the negatively
charged silicoaluminate groups. The strong interaction of the surfactants with
the silicoaluminate surface allows the formation of a monolayerlike structure of
surfactant, which is not observed in the absence of alumina. The synthesis is
slowed by increasing alumina contents due to a destructuration effect of alumina
in the MTSA formation.
PMID- 17034198
TI - Efficient photocatalytic degradation of phenol over Co3O4/BiVO4 composite under
visible light irradiation.
AB - Co3O4/BiVO4 composite photocatalyst with a p-n heterojunction semiconductor
structure has been synthesized by the impregnation method. The physical and
photophysical properties of the composite photocatalyst have been characterized
by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transimission
electron microscopy (TEM), BET surface area, and UV-visible diffuse reflectance
spectra. Co is present as p-type Co3O4 and disperses on the surface of n-type
BiVO4 to constitute a heterojunction composite. The photocatalyst exhibits
enhanced photocatalytic activity for phenol degradation under visible light
irradiation. The highest efficiency is observed when calcined at 300 degrees C
with 0.8 wt % cobalt content. On the basis of the calculated energy band
positions and PL spectra, the mechanism of enhanced photocatalytic activity has
been discussed.
PMID- 17034199
TI - Giant reduction in dynamic modulus of kappa-carrageenan magnetic gels.
AB - Effects of magnetization on the complex modulus of kappa-carrageenan magnetic
gels have been investigated. The magnetic gel was made of a natural polymer,
kappa-carrageenan, and a ferrimagnetic particle, barium ferrite. The complex
modulus was measured before and after magnetization of the gel by dynamic
viscoelastic measurements with a compressional strain. The gels showed a giant
reduction in the storage modulus of approximately 10(7) Pa and also in the loss
modulus of approximately 10(6) Pa due to magnetization. The reduction increased
with increasing volume fraction of ferrite, and it was nearly independent of the
frequency. It was also found that the change in the modulus was nearly
independent of the magnetization direction and irradiation time of the magnetic
fields to the gel. The magnetic gels demonstrating the giant reduction in the
dynamic modulus showed a large nonlinear viscoelastic response. It was observed
that the magnetic gel was deformed slightly due to magnetization. The observed
giant complex modulus reduction could be attributed to the nonlinear
viscoelasticity and deformation caused by magnetization. Magnetism, nonlinear
viscoelasticity, and effects of magnetization on the morphological and shape
changes were discussed.
PMID- 17034200
TI - Viscoelastic micellar solutions in nonionic fluorinated surfactant systems.
AB - The formation and rheological behavior of a viscoelastic wormlike micellar
solution in an aqueous solution of a nonionic fluorinated surfactant,
perfluoroalkyl sulfonamide ethoxylate, of structure C8F17SO2N(C3H7)(CH2CH2O)10H
was studied. Temperature-induced viscosity growth is observed even at low
surfactant concentration (approximately 1 wt %), and viscosity reaches the
maximum at a temperature T(eta)-max. Upon successive increases in the
temperature, the viscosity decreases, and ultimately a phase separation occurs.
Small-angle X-ray scattering (SAXS) measurements confirm the presence of
cylindrical aggregates at low temperature, which undergo continuous one
dimensional growth with increasing temperature, and ultimately, an indication of
a slight lamellarlike structural pattern is observed, which probably comes from
the formation of micellar joints or branching. Such changes in the microstructure
result in a decrease in the viscosity and stress-relaxation time, while the
network structure is retained; the trends in the evolution of shear modulus (Go)
and relaxation time (tauR) with temperature are in agreement with this. With
increased surfactant concentration, the temperature corresponding to the
viscosity maximum (T eta-max) in the temperature-viscosity curve shifts to lower
values, and the viscosity at temperatures below or around T eta-max increases
sharply. A viscoelastic solution with Maxwellian-type dynamic rheological
behavior at low-shear frequency is formed, which is typical of entangled wormlike
micelles. Rheological parameters, eta(o) and Go, show scaling relationships with
the surfactant concentrations with exponents slightly greater than the values
predicted by the living-polymer model, but the exponent of tauR is in agreement
with the theory. Dynamic light-scattering measurements indicate the presence of
fast relaxation modes, associated with micelles, and medium and slow modes,
associated with transient networks. The disappearance of the slow mode and the
predominance of the medium mode as the temperature increases support the
conclusions derived from SAXS and rheometry.
PMID- 17034201
TI - Structural characteristics of a 0.23 mole fraction aqueous solution of
tetrahydrofuran at 20 degrees C.
AB - Hydrogen/deuterium isotopic substitution neutron diffraction techniques were used
to measure the structural correlation functions in a 0.23 mole fraction solution
of tetrahydrofuran in water at room temperature. Empirical potential structure
refinement (EPSR) was used to build a three-dimensional model of the liquid
structure that is consistent with the experimental data. Detailed analysis shows
a preference for nonpolar interactions between the cyclic ether molecules plus
polar interactions between the ether and solvent water and hydrophobic hydration
of the nonpolar regions of the solute. The increase in the number of hydrogen
bond-acceptor sites relative to the number of hydrogen-bond-donor sites in this
system, compared to the balanced situation that would be found in pure water, has
a marked compressive effect on the structure of the solvent. Despite the small
size of the solvent water molecules, the 0.23 mole fraction aqueous solution is
still found to contain small voids akin to those in pure liquid tetrahydrofuran.
In contrast to the positive surface charge of the voids in the pure system, the
average void in this aqueous solution is found to have a net negative charge.
This is due to contributions from the water oxygen atoms that are negatively
polarized by their intramolecular bonding.
PMID- 17034202
TI - Balance of hydrophobic and electrostatic forces in the pH response of weak
polyelectrolyte capsules.
AB - A detailed study of the role of solution pH and ionic strength on the swelling
behavior of capsules composed of the weak polyelectrolytes poly(4-vinylpyridine)
(P4VP) and poly(methacrylic acid) (PMA) with different numbers of layers was
carried out. The polyelectrolyte layers were assembled onto silicon oxide
particles and multilayer formation was followed by zeta-potential measurements.
Hollow capsules were investigated by scanning electron microscopy and atomic
force microscopy. The pH-dependent behavior of P4VP/PMA capsules was probed in
aqueous media using confocal laser scanning microscopy. All systems exhibited a
pronounced swelling at the edges of stability, at pHs of 2 and 8.1. The swelling
degree increased when more polymer material was adsorbed. The swollen state can
be attributed to uncompensated positive and negative charges within the
multilayers, and it is stabilized by counteracting hydrophobic interactions. The
swelling was related to the electrostatic interactions by infrared spectroscopy
and zeta-potential measurements. The stability of the capsules as well as the
swelling degree at a given pH could be tuned, when the ionic strength of the
medium was altered.
PMID- 17034203
TI - Controlling the diameter of carbon nanotubes in chemical vapor deposition method
by carbon feeding.
AB - It was found that the diameter distribution of single-walled carbon nanotubes
(SWNTs) grown by the chemical vapor deposition (CVD) method could be controlled
by the carbon feeding rate at the growth stage. A unified hypothesis on the
relationship between nanoparticle size, growth condition, growth temperature, and
diameter of the resulting nanotubes was developed and used to explain the
relationship. It was shown that the diameters of SWNTs can be controlled even
when highly polydisperse nanoparticles were used as catalyst. Such control
enabled us to synthesize uniform small-diameter SWNTs at low carbon feeding
rates. Additionally, understanding of the important role of the carbon feeding
rate can be used to explain the cause of low growth efficiency in most CVD
processes. It would also help us to design methods to improve the growth
efficiency of CVD growth of nanotubes.
PMID- 17034204
TI - Electron transfer in multiply bridged donor-acceptor molecules: Dephasing and
quantum coherence.
AB - We present a simple theoretical treatment of nonadiabatic electron transfer in
multiply bridged donor-bridge-acceptor molecules using the density matrix
formalism. Destructive interference can result from different signed couplings
between bridge sites, with the simplest system being a four-site Joachim-type
molecular interferometer. Previous work has shown that deposition of energy on
the bridge sites erases the interference and recovers transport. We show that
pure local dephasing, a completely elastic process, is also capable of
eliminating destructive interference and regaining transport. Destructive
interference as a result of system connectivity can explain the familiar ortho
meta-para reactivity of benzene bridges. We also show that pure dephasing can
yield a coalescence of ortho, meta, and para effective coupling strengths and
suggest a system to observe this effect experimentally.
PMID- 17034205
TI - Growth of ZnO nanostructures with different morphologies by using hydrothermal
technique.
AB - ZnO nanostructures, including nanotowers, nanovolcanoes, nanorods, nanotubes, and
nanoflowers, have been grown by using the hydrothermal technique. Most of the ZnO
nanostructures show the perfect hexagonal cross section and well-faceted top and
side surfaces. The basic chemistry and growth mechanism are discussed. By
increasing the reaction time, the volcano-like and tube-like ZnO structures were
formed due to the Ostwald ripening process and the selective adsorption of the
complexes. By using the seed layer, the dense-arrayed, regular oriented ZnO
nanorods were obtained due to the decreased nucleation barrier and the abundant
interfaces as well as the increasing surface roughness.
PMID- 17034206
TI - Temperature-dependent relaxation of excitons in tubular molecular aggregates:
Fluorescence decay and stokes shift.
AB - We report temperature-dependent steady-state and time-resolved fluorescence
studies to probe the exciton dynamics in double-wall tubular J-aggregates formed
by self-assembly of the dye 3,3'-bis(3-sulfopropyl)-5,5',6,6'-tetrachloro-1,1'
dioctylbenzimidacarbocyanine. We focus on the lowest energy fluorescence band,
originating from the inner cylindrical wall. At low temperatures, the experiments
reveal a nonexponential decay of the fluorescence, with a typical time scale that
depends on the emission wavelength. At these temperatures we also find a dynamic
Stokes shift of the fluorescence spectrum and its nonmonotonic dependence on
temperature under steady-state conditions. All these data indicate that below
about 20 K the excitons in the lowest fluorescence band do not reach thermal
equilibrium before emission occurs, while above about 60 K thermalization on this
time scale is complete. By comparing the two lowest fluorescence bands, we also
find indications for fast energy transfer from the outer to the inner wall. We
show that the Frenkel exciton model with diagonal disorder, which previously has
been proposed to explain the absorption and linear dichroism spectra of these
aggregates, yields a quantitative explanation to the observed dynamics. To this
end, we extend the model to account for weak phonon-induced scattering of the
localized exciton states; the spectral dynamics are then described by solving a
Pauli master equation for the exciton populations.
PMID- 17034207
TI - Judd-Ofelt intensity parameters and spectral properties of Gd2O3:Eu3+
nanocrystals.
AB - Three nonequivalent centers of Cs (A, B, and C) in monoclinic phase and C2 and S6
centers in cubic phase were identified in the Gd2O3:Eu3+ nanocrystals with
spectral techniques. Size dependence in the spectra indicated that the
excitations from both host and charge-transfer band (CTB) for the 5D0 --> 7F2
transition of Eu3+ ions were nearly equal for a larger size of 135 nm of the
cubic phase; however, with decreasing the size to or less than 23 nm, the
excitations by the CTB dominated. The variation of excitation leading to the
symmetry and energy change in the C2 and S6 sites was also observed for larger
particle sizes. The Judd-Ofelt intensity parameters Omega(lambda) (lambda = 2, 4)
for Gd2O3:Eu3+ nanoparticles were experimentally determined. The parameters
Omega(lambda) were found to significantly change with the sizes of Gd2O3:Eu3+
from nanoparticles to bulk material. With decreasing the size from 135 to 15 nm,
the quantum efficiencies for 5D0 reduced from 23.6% to 4.6% due to the increasing
ratio of surface to volume.
PMID- 17034208
TI - NIR luminescence intensities increase linearly with proportion of polar thiolate
ligands in protecting monolayers of Au38 and Au140 quantum dots.
AB - The near-infrared photoluminescence of monolayer-protected Au38 and Au140
clusters (MPCs) is intensified with exchange of nonpolar ligands by more polar
thiolate ligands. The effect is general and includes as more polar in-coming
ligands: thiophenolates with a variety of p-substituents; alkanethiolates omega
terminated by alcohol, acid, or quaternary ammonium groups; and thio-amino acids.
Remarkably, place exchanges of the initial phenylethanethiolates on Au38 MPCs by
p-substituted thiophenolates and thio-amino acids and of hexanethiolates on Au140
MPCs by omega-quaternary ammonium terminated undecylthiolates result in increases
in the near-infrared (NIR) luminescence intensities that are linear with the
number of new polar ligands. The increased intensities are systematically larger
for thiophenolate ligands having more electron-withdrawing substituents.
Analogous effects on intensities are observed in the NIR emission of Au140 MPCs
upon place exchange of alkanethiolates with thiolates having short connecting
alkanethiolate chains to quaternary ammonium and to omega-carboxylic acid
termini, and with oxidative charging of the Au cores. The observations are
consistent with sensitivity of the luminescence mechanism to any factor that
enhances the electronic polarization of the bonds between the Au core atoms and
their thiolate ligands. The luminescence is discussed in terms of a surface
electronic excitation, as opposed to a core volume excitation.
PMID- 17034209
TI - A tight-binding method for predicting magnetic ordering in Gd-containing solids:
Application to GdB2C2.
AB - Herein we present a method to compute d-f mediated exchange coupling in Gd
containing systems with a spin-dependent extended Huckel-tight binding (EHTB)
method. EHTB parameters were chosen to exactly reproduce the spin density
functional calculation (SDFT) energy gap of the S = 45/2 and 39/2 spin patterns
for a model compound, Gd6CoI12(OPH3)6. Comparison between SDFT and EHTB results
shows a good match between the spin-pattern energy distribution for the two
methods. We applied our EHTB method to the solid-state compound GdB2C2 by
considering 6 different variations in the ordering of the 4f7 moments.
Calculations indicate that this metallic system should exhibit antiferromagnetic
ordering of the 4f7 moments with a magnetic structure consistent with published
neutron diffraction results.
PMID- 17034210
TI - Pulsating pH-responsive nanogels.
AB - A novel method is presented for the design of robust, sustained
nanochemomechanical oscillators. The approach is based on the switching of
chemoresponsive nanogel beads between their collapsed and swollen state by
coupling them to an appropriately chosen nonlinear reaction. The presented system
utilizes a proton activated oscillatory reaction and pH-sensitive nanobeads of
gel that provide more than an order of magnitude volume change. A key point of
our approach is the control of the colloid stability of the nanobeads of gel in a
wide range of experimental parameters (pH, ionic strength, temperature) without
interfering with the swelling characteristics of the nanogel particles. This was
achieved by utilizing the interaction of nanogels with ionic surfactants.
PMID- 17034211
TI - Enhanced electrical percolation due to interconnection of three-dimensional
pentacene islands in thin films on low surface energy polyimide gate dielectrics.
AB - The role of lateral interconnections between three-dimensional pentacene islands
on low surface energy polyimide gate dielectrics was investigated by the
measurement of the surface coverage dependence of the charge mobility and the use
of conducting-probe atomic force microscopy (CP-AFM). From the correlation
between the electrical characteristics and the morphological evolution of the
three-dimensionally grown pentacene films-based field-effect transistors, we
found that during film growth, the formation of interconnections between the
three-dimensional pentacene islands that are isolated at the early stage
contributes significantly to the enhancement process of charge mobility. The CP
AFM current mapping images of the pentacene films also indicate that the lateral
interconnections play an important role in the formation of good electrical
percolation pathways between the three-dimensional pentacene islands.
PMID- 17034212
TI - Hydrodynamic dimensions, electrophoretic mobility, and stability of hydrophilic
quantum dots.
AB - Luminescent semiconductor quantum dots (QDs) have great potential for use in
biological assays and imaging. These nanocrystals are capped with surface ligands
(bifunctional molecules, amphiphilic polymers, phospholipids, etc.) that render
them hydrophilic and provide them with functional properties. These coatings
alters their hydrodynamic radii and surface charge, which can drastically affect
properties such as diffusion within the cell cytoplasm. Heavy atom techniques
such as transmission electron microscopy and X-ray scattering probe the inorganic
core and do not take into account the ligand coating. Herein we use dynamic light
scattering to characterize the hydrodynamic radius (R(H)) of CdSe-ZnS QDs capped
with various hydrophilic surface coatings (including dihydrolipoic acid and
amphiphilic polymers) and self-assembled QD-protein bioconjugates. Experiments
were complemented with measurements of the geometric size and zeta potential
using agarose gel electrophoresis and laser Doppler velocimetry. We find that the
effects of surface ligands on the hydrodynamic radius and on the nanoparticle
mobility are complex and strongly depend on a combination of the inorganic core
size and nature and lateral extension of the hydrophilic surface coating. These
properties are critical for the design of QD-based biosensing assays as well as
QD bioconjugate diffusion in live cells.
PMID- 17034213
TI - Synthesis and photophysical characteristics of 2,7-fluorenevinylene-based trimers
and their electroluminescence.
AB - Three new 2,7-fluorenevinylene-based trimers were synthesized and characterized.
The synthesis was carried out by the Heck coupling reaction of 9,9-dihexyl-2,7
divinylfluorene with 2-(4-bromophenyl)-5-phenyl-1,3,4-oxadiazole, N,N-diphenyl-4
bromoaniline, or 3-bromopyrene to afford the trimers OXD, TPA, and PYR,
respectively. All the trimers were readily soluble in common organic solvents
such as tetrahydrofuran, dichloromethane, chloroform, and toluene. Their glass
transition temperatures ranged from 33 to 60 degrees C. The UV-vis spectra showed
an absorption maximum at lambda(a,max) = 379-417 nm with optical band gap of Eg =
2.47-2.66 eV. In solution, they emitted strong blue-green photoluminescence (PL)
with PL maximum at lambda(f,max) = 455-565 nm and fluorescence quantum yield of
Phi(f) = 0.65-0.74. On the other hand, in their spin-coated films, the PL
efficiencies significantly decreased due to the presence of concentration
quenching. All samples showed nanosecond transient lifetime containing two
components, suggesting excimer formation. The organic light-emitting diodes
(OLEDs) with OXD and TPA showed green emission with electroluminescence (EL)
quantum efficiencies of eta(EL) approximately 10(-2)%, while very weak EL
efficiency of eta(EL) approximately 10(-5)% was observed with PYR. The highest
occupied molecular orbital (HOMO) levels of the films were found to be 5.05-5.75
eV.
PMID- 17034214
TI - Kinetic prediction of functional group distributions in thermosensitive
microgels.
AB - A kinetic model accounting for the copolymerization of up to four comonomers is
applied to predict both chain and radial functional group distributions in
carboxylic-acid-functionalized poly(N-isopropylacrylamide) (NIPAM)-based
microgels. The model can accurately predict the experimentally observed radial
distributions of functional monomers in microgels prepared using a variety of
different carboxylic-acid-functionalized monomers with significantly different
hydrophobicities, copolymerization kinetics, and reactivities, without requiring
the use of adjustable parameters. Multimodal distributions can both be predicted
and experimentally generated by copolymerizing two -COOH-containing monomers with
widely different reactivities. Chain distributions and monomer block formation
can also be probed using the kinetic model, allowing for qualitative predictions
of the potentiometric titration behavior of the microgels. The kinetic model
reported herein therefore provides the first available analytical method for
semiquantitatively predicting and controlling functional group distributions in
bulk-polymerized microgel systems.
PMID- 17034215
TI - Reactivity of molecularly chemisorbed oxygen on a Au/TiO2 model catalyst.
AB - We present results of an investigation into the reactivity of molecularly
chemisorbed oxygen with CO on a Au/TiO2 model catalyst at 77 K. We previously
discovered that exposing the model catalyst sample to a radio-frequency-generated
plasma jet of oxygen results in co-population of both atomically and molecularly
chemisorbed oxygen species on the sample. We tested the reactivity of the
molecularly chemisorbed oxygen by comparing the CO2 produced from a sample
populated with both species to the CO2 produced from a sample that has been
cleared of molecularly chemisorbed oxygen employing collision-induced desorption.
Samples that are populated with both species consistently result in greater CO2
produced than samples with only atomic oxygen. We interpret this result to
indicate that molecularly chemisorbed oxygen on the sample can directly
participate in the CO oxidation reaction. The reactivity of molecularly
chemisorbed oxygen has been investigated for five different gold coverages (0.5,
0.75, 1, 1.25, and 2 ML), and we observe that there is a greater fractional
difference in the CO2 produced (difference between sample populated with both
molecularly and atomically adsorbed oxygen and sample populated solely with
atomically adsorbed oxygen) for the 1 ML Au coverage than for the other coverages
for equivalent oxygen plasma-jet exposures. However, it is not possible to
unambiguously conclude that this observation is directly related to a particle
size effect on the chemistry since the absolute O(2,a) and O(a) content on the
various surfaces is different for all the coverages studied because of the plasma
jet technique that we employed for populating the surfaces with oxygen.
Unfortunately, this precludes a direct comparison of the reactivity of molecular
oxygen in the carbon monoxide oxidation reaction as a function of gold coverage
and hence particle size.
PMID- 17034216
TI - Single molecule observations of the adsorption sites of methyl isocyanide on
Pt(111) by low-temperature scanning tunneling microscopy.
AB - Scanning tunneling microscopy (STM) has been used to directly investigate the
local structure of methyl isocyanide (CNCH3) adsorbed on Pt(111). At low
coverages, CNCH3 is preferentially adsorbed at on-top sites, in agreement with
earlier deductions based on vibrational spectroscopy. When dosed at low coverages
at 50 K, the molecules tend to adsorb near other CNCH3 molecules with preferred
distances of a and a, where a = 2.78 A is the lattice constant of Pt. Annealing
the surface to 120 K, however, results in a more uniform separation of the
molecules. At higher coverages, the CNCH3 molecules are observed to occupy both
on-top and two-fold bridge sites. On the basis of STM image analysis, CNCH3 forms
an ordered layer of (2 x 3) periodicity at 0.33 ML. Additional details on the
structures of CNCH3 adsorbed at the on-top and two-fold bridge sites are provided
by density functional theory (DFT) calculations. At a coverage that saturates the
first layer (0.33 ML), the occupation ratio for the on-top and two-fold bridge
bonded CNCH3 is 1:1, which is consistent with the results obtained from the
combined use of experimental reflection absorption infrared spectroscopy (RAIRS)
data and DFT calculations.
PMID- 17034217
TI - The impact of the layer thickness on the thermodynamic properties of pd hydride
thin film electrodes.
AB - Recently, a lattice gas model was presented and successfully applied to simulate
the absorption/desorption isotherms of various hydride-forming materials. The
simulation results are expressed by parameters corresponding to several energy
contributions, e.g., interaction energies. However, the use of a model system is
indispensable in order to show the strength of the simulations. The palladium
hydrogen system is one of the most thoroughly described metal hydrides found in
the literature and is therefore ideal for this purpose. The effects of decreasing
the thickness of Pd thin films on the isotherms have been monitored
experimentally and subsequently simulated. An excellent fit of the lattice gas
model to the experimental data is found, and the corresponding parameters are
used to describe several thermodynamic properties. It is analyzed that the
contribution of H-H interaction energies to the total energy and the influence of
the host lattice energy are significantly and systematically changing as a
function of Pd thickness. Conclusively, it has been verified that the lattice gas
model is a useful tool to analyze thermodynamic properties of hydrogen storage
materials.
PMID- 17034218
TI - External electric field effects on absorption and fluorescence spectra of a
fullerene derivative and its mixture with zinc-tetraphenylporphyrin doped in a
PMMA film.
AB - Electroabsorption and electrofluorescence spectra of a fullerene derivative,
C60(C18)2, and its mixture with zinc-tetraphenylporphyrin (ZnTPP) have been
measured by using electric field modulation spectroscopy. The change in dipole
moment is significant in the electroabsorption spectra both of C60(C18)2 and of a
complex composed of C60(C18)2 and ZnTPP, indicating that the excited states both
of C60(C18)2 and of a complex between C60(C18)2 and ZnTPP have a large charge
transfer character. The fluorescence quantum yield of C60(C18)2 decreases in the
presence of an electric field, which probably arises from the field-induced
acceleration of the intramolecular nonradiative process of C60(C18)2 in the
fluorescent state. In a mixture between ZnTPP and C60(C18)2, electrofluorescence
spectra show the field-induced enhancement for the fluorescence of ZnTPP and the
field-induced de-enhancement for the fluorescence both of C60(C18)2 and of the
complex between ZnTPP and C60(C18)2. A theoretical analysis clearly shows that
the field-induced enhancement of the ZnTPP fluorescence in a mixture results from
the field-induced deceleration of the rate of the electron transfer from the
excited ZnTPP to C60(C18)2. The standard free energy gap for the photoinduced
electron-transfer process is estimated based on the theoretical simulation of the
field-dependent fluorescence intensity.
PMID- 17034219
TI - Seed-mediated growth of palladium nanocrystals on indium tin oxide surfaces and
their applicability as modified electrodes.
AB - Palladium nanoparticles (PdNPs) were successfully attached and grown on an indium
tin oxide (ITO) surface using a seed-mediated growth method, i.e., via a simple
two-step immersion of the ITO substrate into the seed and growth solutions. After
the growth treatment for 24 h, PdNPs grew up to 60-80 nm, exhibiting crystal-like
appearances and accompanying the formation of short rodlike nanocrystals as a
minor product. Thus prepared PdNPs tend to stick each other, so that the dense
gathering of PdNPs was observed on the ITO surfaces. Due to the dense attachment,
the PdNPs directly attached to the ITO (PdNP/ITO) electrode had a significantly
lowered charge-transfer resistivity compared with that of a bare ITO, and the
redox reaction of [Fe(CN)6]3-/[Fe(CN)6]4- was observed as reversible in 0.1 M
phosphate buffer solution. The electrocatalytic property of PdNPs was confirmed
for the reduction of oxygen. In addition, some typical responses were observed in
0.5 M H2SO4 with the PdNP/ITO electrode, reflecting both the characteristics of
NPs and the thin layer in nanoscale. The present preparation method of PdNP
attached surfaces would be promising for catalytic applications as well as
electrochemical uses.
PMID- 17034220
TI - Alkaline treatment of iron-containing MFI zeolites. Influence on mesoporosity
development and iron speciation.
AB - The effects of alkaline treatment on the mesoporosity development and iron
speciation in Fe-MFI zeolites have been investigated. To this end, a variety of
samples derived from different synthetic routes and having distinct Si/Al ratios
and Fe content were treated in NaOH solutions and characterized by N2 adsorption,
SEM, TEM, UV/vis spectroscopy, and EPR. The alkaline treatment induces a
significant intracrystalline mesoporosity development by framework silicon
extraction and promotes disintegration of oligomeric iron species. Iron in
framework positions has shown to provoke mesopore formation, whereas nonframework
iron species suppresses silicon leaching and lowers the extent of extra porosity.
PMID- 17034221
TI - Surface-enhanced Raman scattering at the silver electrode/ionic liquid (BMIPF6)
interface.
AB - This is the first report of in situ SER spectra of chemical species adsorbed on a
Ag/room temperature ionic liquid (RTIL) interface. We have investigated the
dependence of the SERS intensity of the RTIL derived from 1-n-butyl-3
methylimidazolium hexafluorophosfate (BMIPF6) adsorbed on a silver electrode. It
has been shown that the BMI+ adsorbs on the silver electrode for potentials more
negative than -0.4 V vs a Pt quasireference electrode (PQRE). In the -0.4 to -1.0
V potential range the SER spectra are similar to the Raman spectrum of the RTIL
BMIPF6. At potentials more negative than -1.0 V some imidazolium ring vibrational
modes and N-CH3 vibrations are enhanced, suggesting that the imidazolium ring is
parallel to the surface and for potentials <-2.8 V the BMI+ is reduced to the BMI
carbene. The potential dependence of the SERS intensities of Py adsorbed on a
silver electrode in BMIPF6 has also been investigated. The results have shown
that at potentials less negative than -0.8 V (vs PQRE) Py adsorbs at an end-on
configuration forming an Ag-N bond. In the -0.9 to -1.4 V potential range Py
molecules lie flat on the electrode surface and at potentials <-1.4 V Py is
replaced by the BMI+. The electrochemical and SERS results have shown that Py has
the effect of changing the oxidation of silver in that medium as well as the
reduction of BMI+ to the BMI carbene. In the presence of Py the BMI+ reduction is
observed at potentials near -2.4 V. The Ag electrode has presented SERS activity
from 0.0 to -3.0 V.
PMID- 17034222
TI - Electrochemically partitioned assembly of organosulfur monolayers and
nanoparticles.
AB - Partitionally assembled organosulfur monolayers were prepared by using an
electrochemically assisted assembly method on gold films that were preseparated
into two regions insulated from each other. Cyclic voltammetry (CV) and X-ray
photoelectron spectroscopy (XPS) were employed to characterize the n
dodecanethiol (DDT) and the 11-mercaptoundecanoic acid (MUA) monolayers, which
were separately assembled on different substrate regions. CV results indicated
that both the DDT- and MUA-coated gold electrodes showed a blocking property
toward the negatively charged redox probe Fe(CN)6(3-). However, when positively
charged Ru(NH3)6(3+) was used as the redox probe, the MUA- and DDT-modified
electrodes showed quasireversible and blocking CV features, respectively. These
phenomena were attributed to different interactions between the negatively
charged MUA surface and the negatively or positively charged redox probes. XPS
spectra obtained on the MUA modified region exhibited an O(1s) peak and a small
discrete C(1s) peak, which arose from the oxygen and the carbon atoms in the
carboxylic acid groups, respectively. For the DDT-modified region, these two
peaks were absent. CV and XPS experimental results provided strong evidence that
different SAMs were selectively deposited onto different regions of the
preexisting patterns of the substrate by electrochemically partitioned assembly.
The partitionally assembled sulfur-based monolayers with different terminal
groups were used to form location-selective nanoparticle assemblies. This
electrochemically partitioned assembly technique has great potential in
controllable constructions of molecular layers and nanostructures on different
surface microarchitectures that are closely integrated on one substrate but
insulated from each other.
PMID- 17034223
TI - Solvent effects on AOT reverse micelles in liquid and compressed alkanes
investigated by neutron spin-echo spectroscopy.
AB - Neutron Spin-Echo (NSE) spectroscopy has been employed to study the interfacial
properties of reverse micelles formed with the common surfactant sodium bis-2
ethylhexyl-sulfosuccinate (AOT) in liquid alkane solvents and compressed propane.
NSE spectroscopy provides a means to measure small energy transfers for incident
neutrons that correspond to thermal fluctuations on the nanosecond time scale and
has been applied to the study of colloidal systems. NSE offers the unique ability
to perform dynamic measurements of thermally induced shape fluctuation in the AOT
surfactant monolayer. This study investigates the effects of the bulk solvent
properties, water content, and the addition of octanol cosurfactant on the
bending elasticity of AOT reverse micelles and the reverse micelle dynamics. By
altering these solvent properties, specific trends in the bending elasticity
constant, k, are observed where increasing k corresponds to an increase in
micelle rigidity and a decrease in intermicellar exchange rate, k(ex). The
observed corresponding trends in k and k(ex) are significant in relating the
dynamics of microemulsions and their application as a reaction media. Compressed
propane was also examined for the first time with a high-pressure, compressible
bulk solvent where variations in temperature and pressure are used to tune the
properties of the bulk phase. A decrease in the bending elasticity is observed
for the d-propane/AOT/W = 8 reverse micelle system by simultaneously increasing
the temperature and pressure, maintaining constant density. With isopycnic
conditions, a constant translational diffusion of the reverse micelles through
the bulk phase is observed, conforming to the Stokes-Einstein relationship.
PMID- 17034224
TI - Dynamic and collective electrochemical responses of tetrathiafulvalene derivative
self-assembled monolayers.
AB - Electroactive tetrathiafulvalene (TTF)-containing alkanethiol self-assembled
monolayers (SAMs) were designed and synthesized to elucidate the relationship
between electrochemical responses and film structures. Two TTF derivative
molecules having one alkanethiol chain (1) and two alkanethiol chains (2) were
utilized to modulate the molecular packing arrangements in the SAMs, and the
formation and structure of the SAMs were characterized by surface plasmon
resonance spectroscopy (SPR). SPR measurements in various contacting media
demonstrated loose packing of SAM 1 and close packing of SAM 2 due to the
different space fillings of the molecules. Two successive one-electron redox
waves were observed for both SAMs by cyclic voltammetry. The peak widths of the
redox waves were strongly dependent on the oxidation states of the TTF moieties,
the packing arrangement of the SAMs, and the contacting medium. We found that TTF
based SAMs exhibited collective electrochemical responses induced by dynamic
structural changes, depending on the degree of freedom for the component
molecules in the SAMs. These results imply that the molecular design, taking into
account the electrochemical responses, extends the available range of molecular
based functionalities in TTF-based SAMs.
PMID- 17034225
TI - Sr(II) in water: A labile hydrate with a highly mobile structure.
AB - Despite the large number of experimental as well as theoretical investigations
available in the literature, some properties of the hydration structure of
Sr(II), for example, the coordination number, are still ambiguous. The presented
molecular dynamics study based on a most suitable ab initio QM/MM protocol
allowed a detailed investigation of structural and dynamical properties of this
hydrate, which shows a considerable degree of internal flexebility as well as
ligand mobility within the first shell. Despite the high computational effort an
exceptionally long QM/MM simulation had to be carried out to obtain sufficient
information to investigate first shell ligand exchange reactions.
PMID- 17034226
TI - Structure and identity of 4,4'-thiobisbenzenethiol self-assembled monolayers.
AB - Self-assembled monolayers (SAMs) of 4,4'-thiobisbenzenethiol (TBBT) can be formed
on Au surface spontaneously. The structural characteristics and adsorption
behavior of TBBT SAMs on Au have been investigated by surface enhanced Raman
scattering (SERS), electrochemical cyclic voltammetry (CV), ac impedance
spectroscopy (EIS), and atomic force microscopy (AFM). It is demonstrated that
TBBT adsorbed on Au by losing a H atom, forming one Au-S bond, and the other
mercapto group is free at the surface of the monolayer owing to the presence of
the nu(S-H) at 2513 cm(-1) and the delta(C-S-H) at 910 cm(-1) in SERS. The
enhancement of the vibration of C-S (1064 cm(-1)), the aromatic C-H vibration
(3044 cm(-1)), and the absence of the vibration of S-S illustrate TBBT adsorbed
on Au forming a monolayer with one benzene ring tilted with respect to the Au
surface. The interpretation of the observed frequencies is aided by ab initio
molecular orbital (MO) calculations at the HF/6-31G level of theory.
Electrochemical CV and EIS indicate TBBT monolayers can passivate the Au
effectively for its low ratio of pinhole defects (theta = 99.6%). AFM studies
give details about the surface morphology. The applications of TBBT SAMs have
been extensively investigated by exposure of Cu2+ ion to TBBT SAMs on Au and
covalent adsorption of metal nanoparticles. Electrochemical, X-ray photoelectron
spectroscopic, and SERS results indicate that Cu2+ can react with TBBT SAMs and
present on TBBT SAMs as Cu(I). A scanning electron microscopic image of Ag
nanoparticles on TBBT/Au and the Raman spectrum of TBBT in smooth macroscopic
Au/TBBT SAMs/Ag nanoparticle sandwich structure indicate that metal nanoparticles
can be adsorbed on TBBT SAMs effectively through covalent linkage.
PMID- 17034227
TI - Infrared spectroscopic investigation of the reaction of hydrogen-terminated,
(111)-oriented, silicon surfaces with liquid methanol.
AB - Fourier transform infrared spectroscopy and first principles calculations have
been used to investigate the reaction of atomically smooth, hydrogen-terminated
Si(111) (H-Si) surfaces with anhydrous liquid methanol. After 10 min of reaction
at room temperature, a sharp absorbance feature was apparent at approximately
1080 cm(-1) that was polarized normal to the surface plane. Previous reports have
identified this mode as a Si-O-C stretch; however, the first principles
calculations, presented in this work, indicate that this mode is a combination of
an O-C stretch with a CH3 rock. At longer reaction times, the intensity of the Si
H stretching mode decreased, while peaks attributable to the O-C coupled stretch
and the CH3 stretching modes, respectively, increased in intensity. Spectra of H
Si(111) surfaces that had reacted with CD3OD showed the appearance of Si-D
signals polarized normal to the surface as well as the appearance of vibrations
indicative of Si-OCD3 surface species. The data are consistent with two surface
reactions occurring in parallel, involving (a) chemical attack of hydrogen
terminated Si(111) terraces by CH3OH, forming Si-OCH3 moieties having their Si-O
bond oriented normal to the Si(111) surface and (b) transfer of the acidic
hydrogen of the methanol to the silicon surface, either through a direct H-to-D
exchange mechanism or through a mechanism involving chemical step-flow etching of
Si-H step sites.
PMID- 17034228
TI - Effect of model potential of adsorptive bond on the thermodynamic properties of
adsorbed CO molecules on Ni(111) surface.
AB - The effect of anharmonicity on the adsorption of CO molecules on the Ni(111)
surface has been investigated. The DFT calculations are used to obtain the
effective adsorption potential of the CO molecule on the Ni(111) surface. First,
using an appropriate slab model, the geometry of adsorption system corresponding
to hcp, fcc, bridge, and on-top sites with p(2 x 2) arrangement and coverage of
0.25 ML is optimized by the DFT calculations using a plane wave basis set and
ultrasoft pseudopotentials; this gives the hcp site as the most stable site with
De = 185 kJ/mol, for which the equilibrium distance of CO from the surface and C
O bond length on the surface are found to be 1.31 and 1.192 A, respectively.
Then, the potential function of adsorption versus adsorptive bond distance was
plotted, which is significantly different from that of a harmonic oscillator,
i.e., the anharmonicity for the adsorptive bond is significant. Also the harmonic
and anharmonic shifts of vibrational frequencies of adsorptive and C-O bonds are
calculated to be -22.6 and 7.8 cm(-1), respectively. Hence, two potential models
are selected for which their Schrodinger equations are solved analytically,
namely the hard repulsion-soft attraction (HS) and Morse potential (MP) models.
The adsorption isotherms, internal energy, isochoric heat capacity, and entropy
of adsorbed CO molecules have been calculated for the mentioned model potentials
and compared with those of the harmonic oscillator (H). As a result, the
adsorption isotherms are not considerably sensitive to the model potential. The
anharmonicity of CO-Ni bond, which is included in HS and MP models, gives an
average deviation in pressure as much as 1.4% for HS and 5.8% for MP, compared to
6.1% for the H model. However, isochoric heat capacity and entropy depend on the
model potential significantly, and the differences may be as high as 69% and 55%
for isochoric heat capacity and entropy, respectively.
PMID- 17034229
TI - Diffusion dynamics of the li atom on amorphous carbon: A direct molecular orbital
molecular dynamics study.
AB - Direct molecular orbital-molecular dynamics (MO-MD) calculation was applied to
diffusion processes of the Li atom on a model surface of amorphous carbon and
compared with the diffusion mechanism of Li+ ion. A carbon sheet composed of
C96H24 was used as the model surface. The total energy and energy gradient on the
full dimensional potential energy surface of the LiC96H24 system were calculated
at each time step in the trajectory calculation. The optimized structure, where
the Li atom is located at the center of mass of the model surface, was used as
the initial structure at time zero. Simulation temperatures were chosen in the
range of 200-1250 K. The dynamics calculations showed that the Li atom vibrates
around the initial position below 250 K, and it moves above 300 K. At middle
temperature, the Li atom translates freely on the surface. At higher temperature
(1000 K), the Li atom moves from the center to edge region of the model surface
and is trapped in the edge. The activation energy calculated for the Li atom is
larger than that for the Li+ ion. This difference is due to the fact that the Li
atom diffuses together with an unpaired electron on the carbon surface. The
diffusion mechanism of the Li atom was discussed on the basis of the theoretical
results.
PMID- 17034230
TI - Understanding the population, coordination, and orientation of water species
contributing to the nonlinear optical spectroscopy of the vapor-water interface
through molecular dynamics simulations.
AB - Molecular dynamics simulations are used to deconvolve the vibrational spectral
features of the vapor-water interface based on molecular environment. A simple
geometric description of hydrogen bonding is deployed to identify the OH stretch
modes that comprise the vibrational sum-frequency spectrum of the vapor-water
interface with direct comparison to our experimental results. The population
densities of different species of water molecules are presented as functions of
interfacial depth and orientation. It is found that surface water molecules that
possess one proton donor bond and one proton acceptor bond make the dominant
contribution to both the SSP- and SPS-polarized spectral responses and are
located within an angstrom of the Gibbs dividing surface.
PMID- 17034231
TI - Computational studies on polymer adhesion at the surface of gamma-Al2O3. I. The
adsorption of adhesive component molecules from the gas phase.
AB - We calculate the minimum energy paths and reaction energies of the adsorption of
the epoxide adhesive components diglycidylesterbisphenol A (DGEBA),
diethyltriamine (DETA), and the adhesion promoter 3-aminopropylmethoxysilane
(AMEO) at two different sites on a model of the native Al2O3 surface, using the
nudged elastic band algorithm in conjunction with self-consistent charge-density
functional based tight binding. Our results show that the chosen combination of
methods is well suited to obtain an overview of the reaction mechanisms and
kinetics of the adsorption of organic molecules on inorganic surfaces. The
obtained MEP-s show that there is preference for the adsorption of the adhesion
promoter, AMEO, over the resin, DGEBA, while the adsorption of the curing agent,
DETA, is unfavorable. Our approach also gives an insight into the ranges of the
mechanical and electronic influences of the adsorption process on the interface,
which neither full ab initio methods nor force field approaches can provide.
These results will help to develop a quantum mechanics-molecular mechanics
multiscale embedding scheme for more detailed studies of organic/inorganic hybrid
interface reactions.
PMID- 17034232
TI - Hydrated arrays of acidic surface groups as model systems for interfacial
structure and mechanisms in PEMs.
AB - We utilize ab initio quantum mechanical calculations in order to explore
structural conformations and cooperative mechanisms at a minimally hydrated 2D
array of flexible acidic surface groups. This system serves as a model for
rationalizing interactions and correlations of protons and water with ionized
side chains that are affixed to hydrophobic polymer aggregates in polymer
electrolyte membranes (PEMs). The model exhibits two basic minimum energy
configurations upon varying the separation of surface groups from 5 to 12 A. In
the "upright" structure at small separation, surface groups are fully dissociated
and oriented perpendicular to the basal plane. Together with hydronium ions
(H3O+) they form a highly ordered network with long-range correlations. At larger
separations we found the transition to a "tilted" structure with cluster-like
conformation of surface groups. This structure retains only short-range
correlations. Moreover, we investigated the strength of water binding to the
minimally hydrated structures. At small separations between surface groups, an
additional water molecule interacts only weakly with the minimally hydrated array
(binding energy < 0.1 eV) while the energy needed to remove one water molecule
exceeds 1 eV. This shows that the minimally hydrated systems are very stable.
Ideally, these studies would expedite the design of cheap, highly performing PEMs
for fuel cells, with a major focus on membranes that could operate stably at
minimal hydration and elevated temperatures (>120 degrees C).
PMID- 17034233
TI - Electrochemical impedance spectroscopy investigations of a microelectrode
behavior in a thin-layer cell: Experimental and theoretical studies.
AB - Electrochemical impedance spectroscopy experiments were performed on a microdisk
electrode in a thin-layer cell using a scanning electrochemical microscope for
controlling the cell geometry. Experimental data showed that when the thin-layer
thickness diminished, an additional low-frequency response appeared. It was
ascribed to the radial diffusion of the electroactive species and was strongly
dependent on the thin-layer dimensions (both thickness and diameter). Moreover,
the numerical simulation of the impedance diagrams by finite element method
calculations confirmed this behavior. An equivalent circuit based on a Randles
type circuit was proposed. Thus, the diffusion was described by introducing two
electrical elements: one for the spherical diffusion and the other for the radial
contribution. A nonlinear Simplex algorithm was used, and this circuit was shown
to fit the impedance diagrams with a good accuracy.
PMID- 17034234
TI - Heteropolyacid-encapsulated self-assembled materials for anhydrous proton
conducting electrolytes.
AB - The composite material of heteropolyacid (12-phosphotungstic acid; PWA) and
polystyrene sulfonic acid (PSS) construct the PWA-encapsulated material by the
self-assembly of -SO3H onto the PWA surface; as a result, the fast proton
transfer occurred at the interface between the PWA and -SO3H, and the
encapsulated material indicated the high anhydrous proton conductivity of 1 x 10(
2) S cm(-1) at 180 degrees C. These anhydrous proton-conducting materials without
the existence of water molecules are quite different from customary ion-exchange
membrane, such as Nafion, and may have advantages as an electrolyte membrane for
polymer electrolyte membrane fuel cells operating at intermediate temperatures
under anhydrous conditions but also for electrochemical devices including
electrochromic displays, chemical sensors, and others.
PMID- 17034235
TI - Molecular dynamics simulations of electrolyte solutions at the (100) goethite
surface.
AB - Molecular dynamics simulations of electrolyte solutions in contact with a neutral
(100) goethite (alpha-FeOOH) surface were used to probe the structure of the
mineral-water interface and gain insight into the adsorption properties of
monovalent ions. Three electrolyte solutions were considered: NaCl, CsCl, and
CsF. The electrolyte ions were chosen to cover a range of ionic sizes and
affinities for the aqueous phase. The molecular dynamics simulations indicate the
presence of a structured interfacial region resulting from the strong interaction
of water with the mineral surface. The specific arrangement and preferred
orientation of water that arise from this interaction create adsorption sites in
the interfacial region, i.e., as far as 15 A away from the surface, and hence
give rise to a strong correlation between the water and ion distributions. The
structure of the hydrated ion, its effect on the water arrangement at the
interface, and the strength of the ion-water bond are found to be key factors
that determine the location and extent of ion adsorption at the interface.
Additionally, in all simulations, we find a build up of positive charges near the
surface due to cation adsorption, which is compensated by an accumulation of
anions in the next few angstroms. This creates an excess of negative charges,
which is in turn compensated by an excess of positive charges, and so on. As we
modeled a neutral surface, the structure of the electrolyte distribution arises
from the complex interplay of the interactions between the surface, water, and
the electrolyte ions rather than from the need to neutralize a surface charge. In
addition, our simulations indicate that the electrolyte distribution does not
resemble that of a classical electrical double layer. Indeed, our calculations
predict the presence of several condensed layers and oscillations in the net
charge away from the surface.
PMID- 17034236
TI - Conductivity percolation in loosely compacted microcrystalline cellulose: An in
situ study by dielectric spectroscopy during densification.
AB - The present study aims at contributing to a complete understanding of the water
induced ionic charge transport in cellulose. The behavior of this transport in
loosely compacted microcrystalline cellulose (MCC) powder was investigated as a
function of density utilizing a new type of measurement setup, allowing for
dielectric spectroscopy measurement in situ during compaction. The ionic
conductivity in MCC was found to increase with increasing density until a
leveling-out was observed for densities above approximately 0.7 g/cm3. Further,
it was shown that the ionic conductivity vs density followed a percolation type
behavior signifying the percolation of conductive paths in a 3D conducting
network. The density percolation threshold was found to be between approximately
0.2 and 0.4 g/cm3, depending strongly on the cellulose moisture content. The
observed percolation behavior was attributed to the forming of interparticulate
bonds in the MCC and the percolation threshold dependence on moisture was linked
to the moisture dependence of particle rearrangement and plastic deformation in
MCC during compaction. The obtained results add to the understanding of the
density-dependent water-induced ionic transport in cellulose showing that, at
given moisture content, the two major parameters determining the magnitude of the
conductivity are the connectedness of the interparticluate bonds and the
connectedness of pores with a diameter in the 5-20 nm size range. At densities
between approximately 0.7 and 1.2 g/cm3 both the bond and the pore networks have
percolated, facilitating charge transport through the MCC compact.
PMID- 17034237
TI - Structural study of NO adsorbed on the reconstructed Pt(110)-(1 x 2) surface with
X-ray photoelectron diffraction and near-edge X-ray absorption fine structure
spectroscopy.
AB - The adsorption structure of NO on the reconstructed Pt(110)-(1 x 2) surface was
studied with X-ray photoelectron spectroscopy (XPS), X-ray photoelectron
diffraction (XPD), low-energy scanned-angle photoelectron diffraction (LESA-PD),
and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. The
experiments were performed at 180 K, where no surface lifting from (1 x 2) to (1
x 1) takes place after NO adsorption. XPS indicates that the (1 x 2) unit cell of
the Pt(110) surface contains 1.5 NO molecules at the saturated coverage. XPD and
LESA-PD analyses allow us to propose a structural model for the NO adlayer, where
two-thirds of the NO molecules in the (1 x 2) unit cell are adsorbed on the atop
site of the close-packed Pt rows (ridges) along the [10] direction with an
inclined geometry and one-third of the NO molecules adsorb on the bridge site
between the Pt ridges with an upright configuration. This model is supported by
the N K-edge NEXAFS experiments and is consistent with the recently reported
model based on the density functional theory (Orita, H.; Nakamura, I.; Fujitani,
T. J. Phys. Chem. B 2005, 109, 10312).
PMID- 17034238
TI - Spacer and anchor effects on the electronic coupling in ruthenium-bis-terpyridine
dye-sensitized TiO2 nanocrystals studied by DFT.
AB - Structural and electronic properties of TiO2 nanoparticles sensitized with a set
of Ru(II)(tpy)2 based dyes have been investigated using density functional theory
(DFT) calculations combined with time-dependent (TD) DFT calculations. The
effects of carboxylic and phosphonic acid anchor groups, as well as a phenylene
spacer group, on the optical properties of the dyes and the electronic
interactions in the dye-sensitized TiO2 nanoparticles have been investigated.
Inclusion of explicit counterions in the modeling shows that the description of
the environment is important in order to obtain a realistic interfacial energy
level alignment. A comparison of calculated electronic coupling strengths
suggests that both the nature of the anchor group and the inclusion of the
phenylene spacer group are capable of significantly influencing electron-transfer
rates across the dye-metal oxide interface.
PMID- 17034239
TI - Enhancement of topographic images obtained in liquid media by atomic force
microscopy.
AB - The open liquid-cell atomic force microscope (AFM) has potential for studies of
biomaterials and surface morphology in liquid media, and a variety of fluids can
be used as buffer solutions. The dependence of image distortion on fluid
properties (kinematic viscosity) has been studied with edge friction force
obtained in lateral images and will shortly appear elsewhere [Appl. Phys. Lett.
2006, 88, 173121]. Previous studies indicate that the scan rate should be slower
for obtaining a nondistorted image. However, the time required for the scan is
greatly increased. Therefore, we introduced the vector concept to evaluate the
net force for scanning in the y-direction and found two solutions to achieve a
zero force difference introduced by the cantilever-fluid and the tip-surface.
When the scan rate approaches zero or a specific velocity (30 microm/s in this
study), the force of the interaction induced by the cantilever-fluid and tip
surface is reduced to a considerable extent. Among the two solutions, a scan with
a specific velocity is an easy, rapid method for obtaining a nondistorted image,
compared to the previously proposed method (scan rate approaches zero). This
proposed model was confirmed in a proof-of-concept test using 2-propanol.
PMID- 17034240
TI - Structuring effects and hydration phenomena in poly(ethylene glycol)/water
mixtures investigated by brillouin scattering.
AB - Aqueous solutions of poly(ethylene glycol) (PEG) of mean molecular mass of 600
g/mol (PEG600) are investigated by Brillouin scattering technique. At high PEG
content, a relaxation phenomenon is observed, which is related to a local
rearrangement of the polymer structure where the interaction, via hydrogen
bonding, with the solvent molecules plays a role. The obtained values of the
relaxation times match the literature data very well for a fast relaxation time
revealed by dielectric relaxation measurements in very similar mixtures. The
calculated concentration behaviors of the excess adiabatic compressibility turns
out in good agreement with the previous findings from ultrasonic measurements at
3 MHz. The observed minimum in the adiabatic compressibility is interpreted as
the result of the interaction between water and the EO units of the PEG chain,
which results in a structure tighter then that typical of bulk water and of pure
PEG600. Such a hypothesis is supported by the observation that volume fraction
value of about 0.3 coincides with the concentration value at which full hydration
of EO units takes place. The observation that at the same concentration, the
polymer coils start to overlap each other further supports the idea that the
adiabatic compressibility behavior is monitoring the structural evolution of the
mixture. However, similar results are obtained for largely different binary
mixture which suggests caution in taking this conclusion too literally. In
particular, the hypothesis that the occurrence of an extreme in the excess
adiabatic compressibility could be simply originated by statistical effects and
that further work is required for disentangling entropic contribution from
effects of hetero-association and self-aggregation of one or both the components.
PMID- 17034241
TI - Critical endpoint and analytical phase diagram of attractive hard-core Yukawa
spheres.
AB - We analytically calculate the gas-liquid critical endpoint (cep) for hard spheres
with a Yukawa attraction. This cep is a boundary condition for the existence of a
liquid. We use an analytical Helmholtz energy expression for the attractive
Yukawa (hard) spheres based on the first-order mean spherical approximation to
the attractive Yukawa potential by Tang and Lu (J. Chem. Phys. 1993, 99, 9828).
This theory and our analytical simplification of it predict the gas-liquid and
fluid-solid phase behavior, as found from computer simulations, very accurately
as long as the range 1/kappa of attraction is not too short. We find that the cep
is situated at kappasigma approximately 6 and at a contact potential around 2 kT.
It follows that a liquid state is only possible when the attraction range is
longer than (1/6) of the particle diameter sigma, and the attraction strength is
smaller than 2 kT. The liquid region does not span more than 0.6 kT in strength,
and there is also a relatively narrow window for the attraction range.
PMID- 17034242
TI - Computational determination of aqueous pKa values of protonated benzimidazoles
(Part 2).
AB - Our aim is to develop an effective computational procedure for predicting the
aqueous acid equilibrium constants of protonated benzimidazoles at 298.15 K. The
experimental determination of these values, apart from been laborious, is a
challenge because of the low water solubility of these compounds. Using a variety
of descriptors, quantitative structure-property relationships (QSPR) are explored
between the experimental aqueous pKa values of a group of fifteen benzimidazoles
and descriptors calculated at the B3LYP/6-31+G(d,p) level of theory. Solvent
effects are taken into account with the PCM solvation model through both single
point energy calculations (PCM(sp)), and in the geometry optimizations and
frequency calculations (PCM(opt)). Descriptors considered are the Gibbs free
energy change of the acid equilibrium in water, the charges on the acidic
hydrogen, and on the basic nitrogen, several orbital energies of the protonated
and neutral species, and the volume of the solvent cavity. Multiple linear
regressions are used to correlate descriptors to the experimental pKa values.
Several QSPR equations reproduce the experimental data more accurately, and show
stronger correlations than previously attempted methodologies. The predictive
capabilities of the QSPR methodologies are tested with four compounds that were
not included in the set of benzimidazoles initially investigated. In addition, a
correlation between experimental pKa values in water and in a 50% ethanol-water
solution is used to estimate aqueous pKa values.
PMID- 17034243
TI - Modeling of folding and unfolding mechanisms in alanine-based alpha-helical
polypeptides.
AB - alpha-Helix formation is known to be opposed by the entropy loss due to the
folding and favored by the energy of molecular interactions. However, the
underlying mechanism of these factors is still being discussed. Here we have used
the experimental and calculation data for short alanine-based peptides embedded
in water to model the mechanism of helix folding and unfolding and to calculate
microscopically the free energy factors of alanine in the frame of helix coil
conformational integrals. Classical helix-coil transition theories take into
account the interactions in a peptide chain only if the i, i + 3 peptide bond
participates in hydrogen bonding. But quantum mechanical calculations showed that
interactions of the i, i + 2 peptide bond play an important role in helix folding
too. We also included the short-range repulsive interactions due to molecular
steric clashes and the end effects due to polar/hydrogen-bonding interactions at
the N and C termini. The helix and coil regions of peptide conformational space
were defined using an experimental steric criterion for hydrogen bonding.
Arginine helix propensity was discussed and estimated. Monte Carlo numerical
simulations of thermodynamics and kinetics for the 21 amino acid alpha-helical
polypeptide Ac-A5(AAARA)3A-NMe were carried out and found to be in an agreement
with the experimental results.
PMID- 17034244
TI - Aggregation of antifreeze protein and impact on antifreeze activity.
AB - Antifreeze protein type III aggregates once the concentration exceeds a critical
value, the so-called critical aggregation concentration (CAC). It was found for
the first time that the aggregation of antifreeze protein exerts a direct impact
on the antifreeze efficiency. It follows from our measurements that the AFP III
above CAC will enhance the antifreeze activity because of the increase of the
kink kinetics barrier of surface integration. This is attributed to the optimal
packing of AFP III molecules on the surface of the ice nucleus as well as ice
crystals above CAC. This study will extend our understanding of the antifreeze
mechanism of antifreeze protein monomers as well as antifreeze aggregates on ice
nucleation and shed light on the selection of antifreeze agents.
PMID- 17034245
TI - Multiple DNA binding modes of a metallointercalator revealed by DNA film
voltammetry.
AB - Binding and the redox reaction of the metallointercalator Ru(bpy)2(dppz)2+ (bpy =
2,2'-bipyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine) with DNA was
investigated by DNA film voltammetry. Calf-thymus DNA (CT-DNA) was assembled on a
tin-doped indium oxide electrode by layer-by-layer electrostatic adsorption.
Voltammetry of Ru(bpy)2(dppz)2+ (Ru-dppz) bound to the DNA film was measured in a
redox-free electrolyte and showed strong dependence on the concentration of the
metallointercalator. At low Ru-dppz concentrations, a single oxidation peak was
observed, the potential of which shifted from 1.25 to 1.1 V with increasing Ru
dppz concentration (peak 1). At high metal chelate concentrations, an additional
oxidation peak emerged with a potential of 1.25 V which was unaffected by the Ru
dppz concentration (peak 2). Three experiments were performed to investigate the
mechanism and structural basis of the multiple peaks. First, voltammetry of
Os(bpy)2(dppz)2+ bound to the CT-DNA film displayed only one peak at its
oxidation potential of about 0.75 V. Second, the concentration dependence of Ru
dppz bound to a poly-(AU) film (which does not contain any guanine bases)
exhibited only one oxidation peak at about 1.22 V that was independent of the Ru
dppz concentration. Third, when the guanine concentration in a mixed film of CT
DNA and poly-(AU) was changed and the bound Ru-dppz was kept constant, a pre-peak
emerged and shifted to 1.1 V with increasing guanines. Based on these results,
the appearance of two peaks in the voltammetric measurements of CT-DNA was
rationalized by invoking two different DNA binding modes for the Ru-dppz complex:
intercalation and electrostatic association. Peak 2 arises from slow oxidation of
guanines catalyzed by Ru-dppz electrostatically associated with the DNA film,
since the addition of Mg2+ decreases the magnitude of peak 2. Peak 1 was not
affected by Mg2+ ions, leading us to conclude that it is due to intercalated Ru
dppz. The intercalation positions the metal complex in close contact with the
guanines inside DNA resulting in fast electrocatalytic reaction, giving rise to a
catalytic pre-peak.
PMID- 17034247
TI - 15N MAS NMR studies of cph1 phytochrome: Chromophore dynamics and intramolecular
signal transduction.
AB - Solid-state nuclear magnetic resonance (NMR) is applied for the first time to the
photoreceptor phytochrome. The two stable states, Pr and Pfr, of the 59-kDa N
terminal module of the cyanobacterial phytochrome Cph1 from Synechocystis sp. PCC
6803 containing a uniformly 15N-labeled phycocyanobilin cofactor are explored by
15N cross-polarization (CP) magic-angle spinning (MAS) NMR. As recently shown by
15N solution-state NMR using chemical shifts [Strauss, H. M.; Hughes, J.;
Schmieder, P. Biochemistry 2005, 44, 8244], all four nitrogens are protonated in
both states. CP/MAS NMR provides two additional independent lines of evidence for
the protonation of the nitrogens. Apparent loss of mobility during
photoactivation, indicated by the decrease of line width, demonstrates strong
tension of the entire chromophore in the Pfr state, which is in clear contrast to
a more relaxed Pr state. The outer rings (A and D) of the chromophore are
significantly affected by the phototransformation, as indicated by both change of
chemical shift and line width. On the other hand, on the inner rings (B and C)
only minor changes of chemical shifts are detected, providing evidence for a
conserved environment during phototransformation. In a mechanical model, the
phototransformation is understood in terms of rotations between the A-B and C-D
methine bridges, allowing for intramolecular signal transduction to the protein
surface by a unit composed of the central rings B and C and its tightly linked
protein surroundings during the highly energetic Pfr state.
PMID- 17034246
TI - Quantification of surface-bound proteins by fluorometric assay: Comparison with
quartz crystal microbalance and amido black assay.
AB - Protein adsorption is of major and widespread interest, being useful in the
fundamental understanding of biological processes at interfaces through to the
development of new materials. A number of techniques are commonly used to study
protein adhesion, but few are directly quantitative. Here we describe the use of
Nano Orange, a fluorometric assay, to quantitatively assess the adsorption of
bovine fibrinogen and albumin onto model hydrophilic (OH terminated) and
hydrophobic (CH3 terminated) surfaces. Results obtained using this method allowed
the calibration of previously unquantifiable data obtained on the same surfaces
using quartz crystal microbalance measurements and an amido black protein assay.
Both proteins were found to adsorb with higher affinity but with lower saturation
levels onto hydrophobic surfaces. All three analytical techniques showed similar
trends in binding strength and relative amounts adsorbed over a range of protein
concentrations, although the fluorometric analysis was the only method to give
absolute quantities of surface-bound protein. The versatility of the fluorometric
assay was also probed by analyzing protein adsorption onto porous
superhydrophobic and superhydrophilic surfaces. Results obtained using the assay
in conjunction with these surfaces were surface chemistry dependent. Imbibition
of water into the superhydrophilic coatings provided greater surface area for
protein adsorption, although the protein surface density was less than that found
on a comparable flat hydrophilic surface. Superhydrophobic surfaces prevented
protein solution penetration. This paper demonstrates the potential of a
fluorometric assay to be used as an external calibration for other techniques
following protein adsorption processes or as a supplemental method to study
protein adsorption. Differences in protein adsorption onto hydrophilic vs
superhydrophilic and hydrophobic vs superhydrophobic surfaces are highlighted.
PMID- 17034248
TI - Intermolecular vibrational coherence in bacteriochlorophyll a with clustered
polar solvent molecules.
AB - We show that resonant impulsive excitation of the Qy absorption band of
bacteriochlorophyll a (BChl) launches a rapidly damped (gamma < 200 fs) ground
state coherent wave-packet motion that arises from intermolecular modes with
clustered solvent molecules. Femtosecond pump-probe, dynamic-absorption signals
were obtained at room temperature with BChl solutions in pyridine, acetone, and 1
propanol. The vibrational coherence observed in the 0-800-fs regime is modeled in
the time domain by two (or three, in the case of 1-propanol) modulation
components with asymmetric, inhomogeneously broadened line shapes and frequencies
in the 100-200-cm(-1) range. The mean frequency of the vibrational coherence
exhibits at least a quadratic dependence on the dipole moment of the solvent
molecules and a y-intercept in the 100-cm(-1) regime. This trend is modeled by an
expression for the natural frequency of a "6-12" potential composed of attractive
terms from van der Waals forces and a repulsive term from the exchange (Pauli
exclusion) force. The model suggests that comparable contributions to the
potential are provided by the dipole-dipole and London dispersion interactions.
These results support the hypothesis that the low-frequency vibrational modes in
the 100-cm(-1) regime that are coupled to the light-driven charge-separation
reactions in the reaction center from purple bacteria are derived from
intermolecular vibrational modes between the chromophores and the surrounding
protein medium.
PMID- 17034249
TI - Assessing induced folding of an intrinsically disordered protein by site-directed
spin-labeling electron paramagnetic resonance spectroscopy.
AB - We used site-directed spin-labeling electron paramagnetic resonance (EPR)
spectroscopy to study the induced folding of the intrinsically disordered C
terminal domain of measles virus nucleoprotein (N(TAIL)). Four single-site
N(TAIL) mutants (S407C, S488C, L496C, and V517C), located in three conserved
regions, were prepared and labeled with a nitroxide paramagnetic probe. We could
monitor the gain of rigidity that N(TAIL) undergoes in the presence of either the
secondary structure stabilizer 2,2,2-trifluoroethanol (TFE) or one of its
physiological partners, namely, the C-terminal domain (XD) of the viral
phosphoprotein. The mobility of the spin label grafted at positions 488, 496, and
517 was significantly reduced upon addition of XD, contrary to that of the spin
label bound to position 407, which was unaffected. Furthermore, the EPR spectra
of spin-labeled S488C and L496C bound to XD in the presence of 30% sucrose are
indicative of the formation of an alpha-helix in the proximity of the spin
labels. Such an alpha-helix had been already identified by previous biochemical
and structural studies. Using TFE we unveiled a previously undetected structural
propensity within the N-terminal region of N(TAIL) and showed that its C-terminal
region "resists" gaining structure even at high TFE concentrations. Finally, we
for the first time showed the reversibility of the induced folding process that
N(TAIL) undergoes in the presence of XD. These results highlight the suitability
of site-directed spin-labeling EPR spectroscopy to identify protein regions
involved in binding and folding events, while providing insights at the residue
level.
PMID- 17034250
TI - Dielectric studies of water clusters in cyclodextrins: Relevance to the
transition between slow and fast forms of thrombin.
AB - Cyclodextrins are useful models in the study of hydrogen bonded water clusters.
In alpha-cyclodextrin hexahydrate (alpha-CD.6H2O), water molecules are ordered
and occupy well-defined positions whereas in the larger beta-cyclodextrin
dodecahydrate (beta-CD.12H2O), there is considerable disorder with water
molecules freely arranged over several possible sites. Here it is shown that beta
CD exhibits substantial structural flexibility and proton mobility compared with
alpha-CD which is relatively very rigid and exhibits negligible short-range
protonic conduction. These properties are directly controlled by the effective
dielectric constant of the molecule, which is determined by the rotational
freedom of water molecules in the hydrogen bond network. This model may be
relevant to proteins where water clusters of this kind are found on the protein
surface and occasionally in the protein interior. The case of thrombin, an
allosteric enzyme incorporating a network of 20 internal hydrogen bonded water
molecules, is discussed.
PMID- 17034251
TI - Methyl dynamics in proteins from NMR slowly relaxing local structure spin
relaxation analysis: A new perspective.
AB - NMR spin relaxation of (2)H nuclei in (13)CH(2)D groups is a powerful method for
studying side-chain motion in proteins. The analysis is typically carried out
with the original model-free (MF) approach adapted to methyl dynamics. The latter
is described in terms of axial local motions around, and of, the methyl averaging
axis, mutually decoupled and independent of the global motion of the protein.
Methyl motion is characterized primarily by the axial squared order parameter,
S(axis)2, associated with fluctuations of the methyl averaging axis. This view is
shown to be oversimplified by applying to typical experimental data the slowly
relaxing local structure (SRLS) approach of Polimeno and Freed (Adv. Chem. Phys.
1993, 83, 89) which can be considered the generalization of the MF approach.
Neglecting mode coupling and the asymmetry of the local ordering and treating
approximately features of local geometry imply inaccurate values of S(axis)2,
hence of the residual configurational entropy derived from it. S(axis)2,
interpreted as amplitude of motion, was found to range from near disorder to
almost complete order. Contrary to this picture, we find with the SRLS approach a
moderate distribution in the magnitude of asymmetric local ordering and
significant variation in its symmetry. The latter important property can be
associated implicitly with the contribution of side-chain rotamer jumps. This is
consistent with experimental residual dipolar coupling studies and theoretical
work based on molecular dynamics simulations and molecular mechanics
considerations. Configurational entropy is obtained in the SRLS approach directly
from experimentally determined asymmetric potentials. Inconsistency between order
parameters from 2H relaxation and from eta(HC-HH) cross-correlation and increase
in order parameters with increasing temperature were observed with the MF
approach. These discrepancies are reconciled, and physically tenable temperature
dependence is obtained with the SRLS approach.
PMID- 17034252
TI - Exploration of the secondary structure specific differential solvation dynamics
between the native and molten globule states of the protein HP-36.
AB - Recent experiments have shown that the time dependence of fluorescence Stokes
shift of a chromophore is substantially different when the chromophore is located
in a molten globule (MG) state and in the native state of the same protein. To
understand the origin of this difference, particularly the role of water in the
differential solvation of the protein in the native and the MG states, we have
carried out fully atomistic molecular dynamics simulations with explicit water of
a partially unfolded MG state of the protein HP-36 and compared the results with
the solvation dynamics of the protein in the folded native state. It is observed
that the polar solvation dynamics of the three helical segments of the protein is
influenced in a nonuniform heterogeneous manner in the MG state. While the
equilibrium solvation time correlation function for helix-3 has been found to
relax faster in the MG state as compared to that in the native state, the decay
of the corresponding function for the other two helices slows down in the MG
state. A careful analysis shows that the origin of such heterogeneous relative
solvation behavior lies in the differential location of the polar probe residues
and their exposure to bulk solvent. We find a significant negative cross
correlation between the contribution (to the solvation energy of a tagged amino
acid residue) of water and the other groups of the protein, indicating a
competing role in solvation. The sensitivity of solvation dynamics to the
secondary structure and the immediate environment can be used to discriminate the
partially unfolded and folded states. These results therefore should be useful in
explaining recent solvation dynamics experiments on native and MG states of
proteins.
PMID- 17034253
TI - Temperature-controlled release of diols from N-isopropylacrylamide-co
acrylamidophenylboronic acid microgels.
AB - N-Isopropylacrylamide-co-acrylamidophenylboronic acid (NIPAM-co-PBA) microgels
were prepared by free radical polymerization in water. The release of glucose and
Alizarin Red S (ARS) from the microgels as a function of temperature has been
investigated by using laser light scattering (LLS) and ultrasensitive
differential scanning calorimetry (US-DSC). Such microgels can bind glucose and
ARS via boronic acids at a lower temperature. As the temperature increases, the
microgels shrink, and the diols are released. The release could be controlled by
temperature. The effect of the structure of the microgels on the release is also
discussed.
PMID- 17034254
TI - Blocking of the nicotinic acetylcholine receptor ion channel by chlorpromazine, a
noncompetitive inhibitor: A molecular dynamics simulation study.
AB - A large series of pharmacological agents, distinct from the typical competitive
antagonists, block in a noncompetitive manner the permeability response of the
nicotinic acetylcholine receptor (nAChR) to the neurotransmitter acetylcholine.
Taking the neuroleptic chlorpromazine (CPZ) as an example of such agents, the
blocking mechanism of noncompetitive inhibitors to the ion channel pore of the
nAChR has been explored at the atomic level using both conventional and steered
molecular dynamics (MD) simulations. Repeated steered MD simulations have
permitted calculation of the free energy (approximately 36 kJ/mol) of CPZ binding
and identification of the optimal site in the region of the serine and leucine
rings, at approximately 4 A from the pore entrance. Coulomb and the Lennard-Jones
interactions between CPZ and the ion channel as well as the conformational
fluctuations of CPZ were examined to assess the contribution of each to the
binding of CPZ to the nAChR. The MD simulations disclose a dynamic interaction of
CPZ binding to the nAChR ionic channel. The cationic ammonium head of CPZ forms
strong hydrogen bonds with Glu262 (alpha), Asp268 (beta), Glu272 (beta), Ser276
(beta), Glu280 (delta), Gln271 (gamma), Glu275 (gamma), and Asn279 (gamma) nAChR
residues. Finally, the conventional MD simulation of CPZ at its identified
binding site demonstrates that the binding of CPZ not only blocks ion transport
through the channel but also markedly inhibits the conformational transitions of
the channel, necessary for nAChR to carry out its biological function.
PMID- 17034255
TI - Monitoring interfacial bioelectrochemistry using a FRET switch.
AB - Generation of functionally active biomolecular monolayers is important in both
analytical science and biophysical analyses. Our ability to monitor the redox
active state of immobilized proteins or enzymes at a molecular level, from which
stochastic and surface-induced variations would be apparent, is impeded by
comparatively slow electron-transfer kinetics and associated signal:noise
difficulties. We demonstrate herein that by covalently tethering an appropriate
dye to the copper protein azurin a highly oxidation-state-sensitive FRET process
can be established which enables redox switching to be optically monitored at
protein levels down to the zeptomolar limit. The surface-potential-induced
cycling of emission enables the redox potential of clusters of a few hundred
molecules to be determined.
PMID- 17034256
TI - Complexation of copper(II)-Chelidamate: A multifrequency-pulsed electron
paramagnetic resonance and electron nuclear double resonance analysis.
AB - Multifrequency electron paramagnetic resonance (EPR) and electron nuclear double
resonance (ENDOR) techniques were used to obtain structural information about the
copper(II)-chelidamate complex. Well-resolved nitrogen ENDOR spectra could be
recorded from solid solution samples by using selective excitation of spin
packets. Evaluation of nuclear quadrupole and dipolar hyperfine interaction of
the directly ligated nitrogen allowed for an identification of the bond direction
to the copper ion within the eigen frame of the copper g-matrix. Invoking two
dimensional EPR techniques, additional hyperfine interaction with a "distant"
nitrogen spin, identified as resulting from the solvent dimethylformamide (DMF),
was observed. The experimental data are only consistent with formation of a
stable pseudoplanar copper complex with single solvent ligation via its oxygen
atom.
PMID- 17034257
TI - Analysis and parametric optimization of 1H off-resonance relaxation NMR
experiments designed to map polypeptide self-recognition and other noncovalent
interactions.
AB - The measurement of 1H off-resonance nonselective relaxation rates (R(theta,ns))
has been recently proposed as an effective method to probe peptide self
recognition, opening new perspectives in the understanding of the
prefibrillization oligomerization processes in amylodogenesis. However, a full
analysis and parametric optimization of the NMR experiments designed to measure
R(theta,ns) relaxation rates is still missing. Here we analyze the dependence of
the R(theta,ns) rates upon three critical parameters: the tilt angle of the
effective field during the spin lock, the static magnetic field, and finally the
repetition delay. Our analysis reveals that the tilt angle theta = 35.5 degrees
not only minimizes spin-diffusion, but also avoids experimental artifacts such as
J-transfer and poor adiabaticity. In addition, we found that when the dominant
relaxation mechanism is caused by uncorrelated pairwise 1H dipole-1H dipole
interactions the R(35.5 degrees,ns) rate is not significantly affected by static
field variations, suggesting a wide applicability of the 1H off-resonance
nonselective relaxation experiment. Finally, we show that the self-recognition
maps based on the comparative analysis of the R(35.5 degrees,ns) rates can
tolerate decreases in the interscan delays without significantly compromising the
identification of critical self-association loci. These considerations not only
provide a better understanding of the 1H off-resonance nonselective relaxation,
but they also serve as guidelines for the optimal setup of this experiment.
PMID- 17034258
TI - Mechanism of ion permeation in a model channel: Free energy surface and dynamics
of K+ ion transport in an anion-doped carbon nanotube.
AB - The mechanism of the ion permeation is investigated for an anion-doped carbon
nanotube, as a model of the K+ channel, by analyzing the free energy surface and
the dynamics of the ion permeation through the model channel. It is found that
the main rate-determining step is how an ion enters the channel. The entrance of
the ion is mostly blocked by a water molecule located at this entrance. Only
about 10% of K+ ions which reach the mouth of the channel can really enter the
channel. The rejection rate sensitively depends on the location of this water
molecule, which is easily controlled by the charge of the carbon nanotube; for
example, the maximum permeation is obtained when the anion charge is at a certain
value, -5.4e in the present model. At this charge, the facile translocation of
the ion inside the channel is also induced due to the number of fluctuations of
the ions inside the channel. Therefore, the so-called "Newton's balls", a toy
model, combined with a simple ion diffusion model for explaining the fast ion
permeation should be modified. The present analysis thus suggests that there
exists an optimum combination of the length and the charge of the carbon nanotube
for the most efficient ion permeation.
PMID- 17034260
TI - Comparative computational analysis of different active site conformations and
substrates in a chalcone isomerase catalyzed reaction.
AB - Chalcone isomerase catalyzes the transformation of chalcones to flavanones. We
present a computational study of the rate-limiting chemical step, an
intramolecular Michael addition of a 2'-oxyanion to the alpha,beta-double bound.
By using quantum mechanical/molecular mechanical hybrid methods we traced the
free-energy profiles associated with the reaction of two different substrates
(chalcone and 6'-deoxychalcone) in two different conformations of the active site
that are described in the different crystallographic structures available. We
have obtained significant differences (about 4 kcal/mol) in the free-energy
barriers calculated for the two active sites. According to our results, the
active site conformation with larger catalytic power presents a positively
charged lysine residue much closer to the substrate than the other. Complementary
electronic and electrostatic analysis shows that the charge is transferred from
the 2'-oxyanion to the beta-carbon atom. Interactions of the environment with
these two atoms are essential to understand the differences between both active
sites and also the origin of catalysis in this enzyme.
PMID- 17034259
TI - Role of aspartic acid in collagen structure and stability: A molecular dynamics
investigation.
AB - A molecular dynamics (MD) simulation study has been carried out to understand the
stability of the triple helical collagen models. The calculations show that the
presence of the aspartic acid residue in different positions leads to the local
variation in the structure. Analyses of root-mean-square deviation (RMSD), radial
distribution function (RDF), puckering effect, dihedral angle variation, hydrogen
bond (H-bond), and conformational changes during molecular dynamics simulation
reveal that the local perturbation in the sequences, increase in chain
flexibility due to removal of five membered rings in the collagen by aspartic
acid, change of intermolecular H-bonding pattern, and differences in the
association of water are mainly influencing the nature of stabilization of
collagen by aspartic acid.
PMID- 17034261
TI - Contributions of hydroxyethyl groups to the DNA binding affinities of anthracene
probes.
AB - Contributions of hydroxyethyl functions to the DNA binding affinities of
substituted anthracenes are evaluated by calorimetry and spectroscopy. Isothermal
titration calorimetry indicated that binding of the ligands to calf thymus DNA (5
mM Tris buffer, 50 mM NaCl, pH 7.2, 25 degrees C) is exothermic. The binding
constants increased from 1.5 x 10(4) to 1.7 x 10(6) M(-1) as a function of
increase in the number of hydroxyethyl functions (0-4). DNA binding was
accompanied by red-shifted absorption (approximately 630 cm(-1)), strong
hypochromism (>65%), positive induced-circular dichroism bands, and negative
linear dichroism signals. DNA binding, in general, increased the helix
stabilities to a significant extent (DeltaT(m) approximately 7 degrees C,
DeltaDeltaH approximately 3 kcal/mol, DeltaDeltaS approximately 6-20 cal/K.mol).
The binding constants showed a strong correlation with the number of hydroxyethyl
groups present on the anthracene ring system. Analysis of the binding data using
the hydrophobicity parameter (Log P) showed a poor correlation between the
binding affinity and hydrophobicity. This observation was also supported by a
comparison of the affinities of probes carrying N-ethyl (Kb = 0.8 x 10(5) M(-1))
versus N-hydroxyethyl side chains (Kb = 5.5 x 10(5) M(-1)). These are the very
first examples of a strong quantitative correlation between the DNA binding
affinity of a probe and the number of hydroxyethyl groups present on the probe.
These quantitative findings are useful in the rational design of new ligands for
high-affinity binding to DNA.
PMID- 17034263
TI - Enhancement of lithium amide to lithium imide transition via mechanical
activation.
AB - The decomposition of lithium amide (LiNH2) to lithium imide (Li2NH) and ammonia
(NH3) with and without high-energy ball milling is investigated to lay a
foundation for identifying methods to enhance the hydrogen uptake/release of the
lithium amide and lithium hydride mixture. A wide range of analytical instruments
are utilized to provide unambiguous evidence of the effect of mechanical
activation. It is shown that ball milling reduces the onset temperature for the
decomposition of LiNH2 from 120 degrees C to room temperature. The enhanced
decomposition via ball milling is attributed to mechanical activation related to
the formation of nanocrystallites, the reduced particle size, the increased
surface area, and the decreased activation energy. The more mechanical activation
there is, then the more improvement there is in enhancing the decomposition of
LiNH2. It also is found that the activation energy for the decomposition of LiNH2
without ball milling is 243.98 kJ/mol, which is reduced to 222.20 kJ/mol after
ball milling at room temperature for 45 min and is further reduced to 138.05
kJ/mol after ball milling for 180 min. The rate of the isothermal decomposition
at the later phase of the LiNH2 decomposition is controlled by diffusion of NH3
through the Li2NH layer.
PMID- 17034262
TI - Cryogenic photolysis of activated bleomycin to ferric bleomycin.
AB - Activated bleomycin (ABLM) is a drug--Fe(III)-hydroperoxide complex kinetically
competent in DNA attack (via H4' abstraction). This intermediate is relatively
stable, but its spontaneous conversion to ferric bleomycin (Fe(III).BLM) is
poorly characterized because no observable intermediate product accumulates.
Light was shown to trigger ABLM attack on DNA in liquid at -30 degrees C, so ABLM
was irradiated (at its 350 nm ligand-to-metal charge-transfer transition) at 77 K
to stabilize possible intermediates. ABLM photolysis (quantum yield, Phi = 0.005)
generates two kinds of product: Fe(III).BLM (with no detectable intermediate) and
one or more minor (1-2%) radical O-Fe-BLM byproduct, photostable at 77 K. Adding
DNA, even without its target H4', increases the quantum yield of ABLM conversion
>10-fold while suppressing the observed radical yield. Since cryogenic solid
phase reactions can entail only constrained local rearrangement, the reaction(s)
converting ABLM to Fe(III).BLM must be similarly constrained.
PMID- 17034264
TI - Comment on "Examination of spinel and nonspinel structural models for gamma-Al2O3
by DFT and Rietveld refinement simulations".
PMID- 17034265
TI - Comment on "Examination of spinel and nonspinel structural models for gamma-Al2O3
by DFT and Rietveld refinement simulations".
PMID- 17034267
TI - Driving: the ultimate IADL.
PMID- 17034268
TI - Driver safety in older adults. The physician's role in assessing driving skills
of older patients.
AB - Physicians play an important role in addressing driving safety issues with their
patients. This is especially true when age-associated changes, medical conditions
and medications are likely to increase crash risk. Unfortunately, physicians have
little or no training in determining crash risk. Furthermore they are reluctant
to alienate their patients by raising concerns about driving. In response to a
growing need, the American Medical Association (AMA), with support from the
National Highway Traffic Safety Administration (NHTSA), has produced materials to
help physicians approach this issue. This article provides background about the
aging and medical influences on driving, a summary of selected information from
the AMA guide, and additional resources.
PMID- 17034269
TI - Patient reports six-month history of minimally pruritic purple dots on legs. Non
blanching macules developed over six months.
PMID- 17034270
TI - Alcohol use in the elderly: beyond the CAGE. Part 1 of 2: prevalence and patterns
of problem drinking.
AB - It has been estimated that 33% of adults age 65 and older have consumed alcohol
during the preceding month; 25% of these drinkers (31% of men, 19% of women)
drink daily and approximately 10% drink five drinks on one occasion. Alcohol
misuse, with or without dependence, increases an older patient's risks of
physical and mental problems. Yet hazardous drinking often is not identified in
the elderly because ageism, denial, coexisting disabilities, and the unique
pattern of late-onset drinking frequently mask its presence and complicate the
diagnosis.
PMID- 17034271
TI - Chemiluminescence associated with singlet oxygen reactions with amino acids,
peptides and proteins.
AB - Low level chemiluminescence (CL) is observed after protein oxidation mediated by
singlet oxygen produced in Rose Bengal (RB) irradiation. This CL lasts for
several minutes after the end of the photolysis. In this work, the mechanism of
the process was assessed from the spectral characteristics of the CL and the
effect of antioxidants (Trolox or ascorbate), Ebselen (a compound with peroxidase
like activity), azide (a singlet oxygen scavenger) and D2O, added prior to or
after RB irradiation. It is concluded that most of the light emission is due to
formation of excited states generated in the decomposition of peroxides and/or
hydroperoxides accumulated during the photolysis. Experiments carried out in the
presence of several amino acids (Cys, Met, His, Tyr and Trp) and di- and
tripeptides suggest that peroxides (and/or hydroperoxides) of Trp residues are
mainly responsible for the CL observed after singlet oxygen-mediated protein
oxidation. The much weaker CL observed after the oxidation of proteins without
Trp residues supports this conclusion. A comparison of the results obtained
employing free Trp, Ala-Trp and Trp-Ala dipeptides, Ala-Trp-Ala tripeptide and
Trp-containing proteins supports the conclusion that blocking the amino group of
the Trp moiety strongly increases the efficiency of the chemiluminescent process,
producing approximately 2.5x10(-8) photons per oxidized Trp group in Ala-Trp. A
mechanism comprising two chemiluminescent oxidation pathways of Trp residues is
proposed to explain the results.
PMID- 17034273
TI - Exploring the other side of acupuncture.
PMID- 17034274
TI - A perspective on the emergence of meditation techniques for medical disorders.
PMID- 17034275
TI - Physicians' personal and practice use of cam therapies in a rural community in
the southeast United States.
PMID- 17034276
TI - Developing a reliable nematode assay.
PMID- 17034277
TI - Women's reasons for complementary and alternative medicine use: racial/ethnic
differences.
AB - OBJECTIVES: Although racial/ethnic differences in the prevalence of complementary
and alternative medicine (CAM) utilization have been documented, differences in
the reasons for using CAM have not been empirically assessed. In an increasingly
diverse society, understanding differences in rates of and reasons for CAM use
could elucidate cultural and social factors of health behaviors and inform health
care improvements. The current study examines reasons for CAM use among women in
four racial/ethnic groups. DESIGN: A national telephone survey of 3172 women aged
18 years and older was conducted in four languages. Respondents were asked about
their use of remedies or treatments not typically prescribed by a medical doctor.
This study focuses on those women who used CAM in the previous year and their
reasons for using CAM. RESULTS: Non-Hispanic white women were most likely to cite
personal beliefs for CAM use. Cost of conventional medicine was most prevalent
among Mexican-American women CAM users. Physician referral, family and friends,
and media sources were all equally likely to lead to CAM use in non-Hispanic
white women. In contrast, informal networks of family and friends were the most
important social influences of CAM use among African-, Mexican-, and Chinese
American women. CONCLUSIONS: Racial/ethnic differences in reasons for CAM use
highlight cultural and social factors that are important to consider in public
evaluation of the risks and benefits of CAM remedies and treatments.
PMID- 17034278
TI - Homeopathic combination remedy in the treatment of acute childhood diarrhea in
Honduras.
AB - BACKGROUND: Despite the widespread availability of oral rehydration therapy,
diarrheal illness remains a major cause of morbidity and mortality around the
world. Previous studies have shown individualized homeopathic therapy to be
effective in treating childhood diarrhea, but this approach requires specialized
training. OBJECTIVE: A homeopathic combination medicine, if effective, could be
used by health personnel on a widespread basis. METHODS: A double-blind
randomized controlled trial was conducted in Honduras to evaluate the
effectiveness of a homeopathic combination therapy to treat acute diarrhea in
children. A total of 292 children with acute diarrhea was recruited; 145 were
randomized to the experimental group and 147 to the placebo group. Tablets
containing a combined preparation of the five most common single homeopathic
remedies used to treat diarrhea or placebo were administered by a parent after
each unformed stool. Children were followed up daily for 7 days or until symptoms
resolved, whichever occurred first. Time until resolution of symptoms, daily rate
of unformed stools, and total number of unformed stools were compared between the
two groups. RESULTS: There was no significant difference in the likelihood of
resolution of diarrheal symptoms between the treatment and placebo groups (hazard
ratio = 1.02, 95% confidence interval: 0.79-1.32), with a median time until
resolution of 3 days for both groups. Children in the treatment group had an
average of 2.6 unformed stools per day compared to 2.8 among those in the placebo
group; this difference was not significant (p = 0.43). The median number of
unformed stools was 7 among children in the treatment group and 8 among those in
the placebo group (p = 0.41). DISCUSSION: The homeopathic combination therapy
tested in this study did not significantly reduce the duration or severity of
acute diarrhea in Honduran children. Further study is needed to develop
affordable and effective methods of using homeopathy to reduce the global burden
of childhood diarrhea.
PMID- 17034279
TI - Designing an acupuncture study: II. The nationwide, randomized, controlled German
acupuncture trials on low-back pain and gonarthrosis.
AB - BACKGROUND: In the nationwide German Acupuncture Trials (GERAC), verum
acupuncture, mirroring the Traditional Chinese Medicine (TCM) acupuncture style,
was tested against sham acupuncture and guideline standard therapy for the
entities classified in the West as chronic low back pain (LBP) and gonarthrosis
(GON). OBJECTIVE: The objective was to develop broadly consensual acupuncture and
control protocols for the treatment of LBP and GON in the GERAC trials.
METHODOLOGY: Extensive literature study and consultation with acupuncture experts
were consulted. Personal interviews, both free and structured, e-mail
discussions, and phone conferences were used as well. RESULTS: Broadly consensual
acupuncture protocols for LBP and GON for verum and invasive sham acupuncture
were developed. They included semistandardized point combinations with clearly
described point selection rules based on TCM acupuncture diagnosis. A procedure
was developed to help ensure homogenous treatment quality in a large multicenter
trial. CONCLUSIONS: With 1162 randomized patients for LBP and 1039 patients for
GON, the GERAC study design allowed acupuncture to be tested in a naturalistic
environment. The rigorous study design and large number of physician
investigators guaranteed a high external validity for the results. The results
will help determine the significance of Chinese acupuncture in the context of
Western medicine for the treatment of LBP and GON.
PMID- 17034280
TI - The electrophysiology of de qi sensations.
AB - OBJECTIVE: The objective was to investigate the effect of three different modes
of stimulation on: (1) the electrical conductance of a known acupuncture point
(AP) and a point with no known acupuncture function (NP); and (2) the
corresponding characteristics of de qi sensations. DESIGN: The design was
prospective. SETTINGS AND LOCATIONS: Healthy subjects were recruited for the
study at the University of California, San Diego Medical Center. Subjects and
Study Interventions: Fifteen subjects were enrolled. Two locations of the
subjects' nondominant hand were marked: (1) AP (Li4); and (2) NP, a control
location with no known acupuncture function. The following different stimulation
paradigms were applied to the testing sites in a randomized fashion: (1)
transcutaneous electrical stimulation via an ECG electrode; (2) manual
stimulation via an acupuncture needle; and (3) electrical stimulation via an
acupuncture needle. All electrical stimulation was provided at 12 V and 5 Hz for
30 seconds. OUTCOME MEASURES: The conductance before and after each stimulation
were measured. The subjects were asked to choose four most predominant
descriptors of the de qi sensation after the stimulation and to rate the
corresponding intensity on a linear VAS. RESULTS: The conductance values at the
AP site are generally a bit higher than conductance values at the NP site for
each given stimulation type. The de qi VAS score increased significantly after
needle electrical stimulation (EA) in comparison to electrode or manual
stimulation at both sites. The most predominant (incidence >30%) de qi sensation
with electrical stimulation in either electrode or needle electrical stimulation
was tingling, whereas in the manual stimulation, aching was the most predominant
sensation of de qi. CONCLUSIONS: The de qi sensation appears to be qualitatively
and quantitatively different between manual and electrical stimulation. The
observed difference in transcutaneous electrical conductance between.
PMID- 17034281
TI - Establishment of a discriminant mathematical model for diagnosis of deficiency
cold syndrome using gene expression profiling.
AB - OBJECTIVE: To screen diagnostic markers of Deficiency-Cold syndrome by gene
expression profile and to establish a discriminant mathematical milliliters model
for the clinical diagnosis of this syndrome based on a support vector machine
(SVM). METHODS: A family suffering from Deficiency-Cold syndrome is chosen for
this study. This family has 5 patients with Deficiency-Cold syndrome and 10
normal members. The peripheral blood samples for these 5 patients and 5 normal
members are tested by using cDNA microarray with 18,816 clones to get their
differential expression genes. These genes are further explored to understand
their biological functions and pathways through existing databases. A SVM model
for clinical diagnosis is then developed based on these differential expression
genes. RESULTS: A total of 83 differential expression genes were identified
between patients and normal members, in which 21 genes were recorded in the
FATIGO database and 16 genes were related to metabolism. Eight (8) pathways were
sorted out in the KEGG database, and half pathways were associated with human
metabolism. A discriminant mathematical model based on a support vector machine
successfully predicted a normal person and a patient with heavy Deficiency-Cold
syndrome based on their gene differential expression profiles. Thus, this model
may classify the Deficiency-Cold syndrome. CONCLUSION: This work demonstrates
that the differential expression genes can be used to identify normal persons and
patients with Deficiency-Cold syndrome. Deficiency-Cold syndrome is mainly
associated with the metabolism-related gene regulations. In addition, the
discriminant mathematical model based on a support vector machine is applicable
to the clinical diagnosis for Deficiency-Cold syndrome.
PMID- 17034282
TI - Traditional chinese medicine for the treatment of chronic prostatitis in China: a
systematic review and meta-analysis.
AB - OBJECTIVE: To systematically evaluate the effectiveness of Chinese herbal
medicine for treating chronic prostatitis (CPT) in China. DESIGN: Electronic
medical database from China National Knowledge Infrastructure (CNKI) was
searched, language is Chinese; date is from January 1, 1994 to December 31, 2003.
A total of 108 trials were found, and all studies with words like "randomization"
or "quasi-randomization" in their abstracts were included, whether they used
blinding or not. Nineteen theses that met the entry criteria were downloaded and
fully printed. Four groups were divided: Chinese herbs orally treated group
(based on syndrome differentiation), Chinese herbs externally treated group,
Chinese herbs orally and externally treated group, and integrated Western with
Chinese herbs treated group. RESULTS: All 19 articles that met the entry criteria
were clinical trial studies with low quality (Jadad Score <3). The results showed
that Traditional Chinese Medicine (TCM) may benefit the patients who had CPT.
However, from the results of the funnel plots analysis of all four groups of
clinical trials that met the inclusion criteria in this systematic review are
distant asymmetrical and irregular plots, which indicate that a positive
publication bias may exist. There was no obvious evidence indicating that the
efficacy of the therapy in the treated groups using TCM was superior to that of
the control group (Western medicine treatment group). CONCLUSIONS: All of the
four groups in the clinical trials have not provided evidence of evidence-based
medicine (EBM) A class (including 1a, 1b, 1c level), failed to prove that the TCM
may have beneficial effects for patients with CPT, because of low quality in all
the trials and a positive publication bias. Therefore, in light of some positive
outcomes, a good design of multicentered, randomized, parallel-controlled and
blinding trials is needed in order to make further studies, and deserve further
examination for the treatment of CPT with TCM.
PMID- 17034283
TI - Clinical studies of immunomodulatory activities of Yunzhi-Danshen in patients
with nasopharyngeal carcinoma.
AB - OBJECTIVES: Nasopharyngeal carcinoma (NPC) is a prevalent tumor in Hong Kong. The
immune system of such patients could be adversely affected during the course of
conventional chemotherapy or radiotherapy. We investigated the immunomodulatory
effects of Traditional Chinese Medicine (TCM) Yunzhi-Danshen capsules in NPC
patients treated with radiotherapy. DESIGN: Randomized, double-blind, placebo
controlled 16-week study. SETTING/LOCATION: The Prince of Wales Hospital, the
Chinese University of Hong Kong, Hong Kong. SUBJECTS: Twenty-seven (27) patients
with histologically proven NPC, at least 18 years of age. METHODS: Twenty-seven
patients with histologically proven NPC were recruited to take Yunzhi (3.6 g
daily) and Dangshem (1.4 g daily) in the form of 12 combination capsules (TCM
group) or placebo (12 capsules) daily for 16 weeks, respectively. Flow cytometry
was used to assess the percentages and absolute counts of human lymphocyte
subsets in whole blood. Plasma concentration of soluble interleukin-2 receptor
and soluble tumor necrosis factor receptor 2 was measured by enzyme-linked
immunosorbent assay (ELISA). Ex vivo production of tumor necrosis factor-alpha,
interleukin (IL)-6, and IL-10 in the whole blood assay culture supernatant was
measured by ELISA. RESULTS: The decreases in percentage and absolute count of T
lymphocytes in the TCM group were less than those in the placebo group after they
took the capsules for 16 weeks (both p < 0.05). Furthermore, the decreases in
absolute count of T suppressor cells plus cytotoxic T lymphocytes, and T helper
cells in the TCM group were significantly lower than those in the placebo group
after they took the capsules for 16 weeks (both p < 0.05). CONCLUSION: These
results suggest that Yunzhi-Danshen can exert an immunomodulating effect in
alleviating lymphopenia during radiotherapy in NPC patients.
PMID- 17034284
TI - Comparative studies of various ganoderma species and their different parts with
regard to their antitumor and immunomodulating activities in vitro.
AB - OBJECTIVES: Ganoderma lucidum (Lingzhi or Reishi) has been commonly suggested in
East Asia as a potential candidate for prevention and treatment of different
diseases, including cancer. Ganoderma extracts, in particular Ganoderma lucidum
(extracts or isolated components), have previously been shown to possess
antitumor activities. The present study aimed at comparing three different
species of Ganoderma, wildly grown versus cultivated, as well as the different
parts of the fruiting body (whole fruiting body, pileus, and stipe), with regard
to their antitumor effects in human breast cancer cells and immunomodulatory
activities in mouse splenic lymphocytes in vitro. METHODS: The aqueous extracts
(12.5-400 microg/mL) of G. lucidum, G. sinense, and G. tsugae were examined for
their antiproliferative activities in human breast cancer cell lines, MCF-7 and
MDA-MB-231, as well as in normal human mammary epithelial cells (primary
culture). The immunomodulatory effects of the extracts were evaluated in mouse
splenic lymphocytes. The proliferative responses of the mentioned cell types were
determined by MTT [3-(4,5-dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide]
assay. RESULTS: The present results demonstrated that the extracts of all tested
Ganoderma samples could significantly inhibit cell proliferation in human breast
cancer cell lines MCF-7 and MDA-MB-231, with G. tsugae being the most potent. The
extracts, however, did not exert any significant cytotoxic effect on human normal
mammary epithelial cells. Within the species G. sinense, the inhibitory effects
of wildly grown samples were not significantly different from those of the
cultivated samples, except at 400 microg/mL. Most of the tested extracts of
Ganoderma stimulated mouse splenic lymphocytes proliferation. The extracts from
the stipes of the G. tsugae and wildly grown G. sinense showed much stronger
inhibitory effects than the other parts of the fruiting body in both cancer cell
lines, whereas the extracts from the stipes of G. lucidum and wildly grown G.
sinense showed stronger immunopotentiating activities in mouse splenic
lymphocytes. CONCLUSIONS: These results indicate that the aqueous extracts of
these commonly available Ganoderma fruiting bodies, G. lucidum, G. sinense, and
G. tsugae have antitumor activities in human breast cancer cells and
immunomodulatory activities in murine lymphocytes. In addition, the present
findings also suggest that the stipes of fruiting bodies of Ganoderma species
should be included in the preparation of extract of these fungi in order to
obtain the most comprehensive active ingredients. To the best of the authors'
knowledge, this is the first detailed comparison among the different parts of the
fruiting bodies of Ganoderma.
PMID- 17034285
TI - Consulting a complementary and alternative medical practitioner: a systematic
inventory of motives among French patients.
AB - OBJECTIVES: To classify people's motives for seeking care from complementary and
alternative medicine practitioners. Participants were asked about a wide variety
of motives representing all eight motivational states described in Reversal
Theory (RT): telic, paratelic, conformist, negativist, mastery, sympathy, autic,
and alloic. DESIGN: Data from a convenience sample of 256 participants was
examined using factorial techniques. RESULTS: Six factors were evidenced that
were easily interpretable in the RT framework. Participants perceived their
motives largely in terms of goals and means, and within this domain they focused
more on the goals (i.e., telic motives were more important than paratelic ones).
Paratelic motives were, however, not unimportant: they ranked third. Participants
also perceived their motives in terms of rules and constraints, and within this
domain they focused more on rules (i.e., conformist motives were more important
than negativist ones). Participants, finally, perceived their motives in terms of
the combined domains of relationships and exchanges with others, namely, acting
out of concern for others (alloic sympathy) as well as for themselves (autic
mastery). CONCLUSIONS: If the six-factor structure is proved applicable, the six
corresponding subscales could be used for systematically comparing motives among
different types of patients, regarding different types of therapies, and among
patients from different cultures.
PMID- 17034286
TI - Quality of life in patients treated with Kampo medicine: a complementary
alternative to modern medicine.
AB - OBJECTIVE: Kampo (Japanese traditional herbal medicine) is widely used as a
complementary medicine for improving the quality of life (QOL) of patients in
Japan. We investigated the efficacy of kampo therapy in improving QOL of patients
with various diseases and disorders, using the World Health Organization Quality
of Life Brief Scale (WHOQOL-BREF). DESIGN, SETTING, AND PARTICIPANTS: One hundred
and sixty-seven outpatients with various diseases or disorders wishing to receive
kampo therapy and who had already been treated with modern medicines were
recruited into the study. Patients were offered kampo formulas and modern
medicines for 3 months. MAIN OUTCOME MEASURES: Scores of WHOQOL-BREF and Clinical
Global Impression (CGI) Global Improvement scale, and adverse events. RESULTS:
Eleven patients were "very much improved," 46 were "much improved," 59 were
"minimally improved," 42 showed "no change," 7 were "minimally worse," and one
was "much worse" in the CGI Global Improvement scale. The mean WHOQOL-BREF score
improved significantly from 3.05 +/- 0.54 at baseline to 3.14 +/- 0.53 after 3
months (p = 0.002). CONCLUSION: Patients presenting with various diseases and
disorders were successfully treated with kampo therapy. Our results suggest that
kampo therapy as a complementary medicine may improve the QOL of patients with
various diseases and disorders.
PMID- 17034287
TI - Use of complementary and alternative medicine among adults with chronic diseases:
United States 2002.
AB - BACKGROUND: Use of Complementary and Alternative Medicine (CAM) has increased in
recent years. OBJECTIVE: The aim of this study was to determine the use of CAM
among people with diagnosed chronic diseases. DESIGN: Cross-sectional analysis
was used. SETTING: The 2002 National Health Interview Survey was the setting.
PATIENTS: Participants were representative of the noninstitutionalized U.S.
population 18 years and older. MEASUREMENTS: Respondents answered questions about
use of CAM and physician-diagnosed arthritis, cancer, cardiovascular disease,
diabetes, and lung disease. RESULTS: Adults with diagnosed chronic diseases are
more likely to use CAM compared to adults with none of the reported chronic
diseases. Adults with arthritis alone were most likely to report ever use of CAM
(59.6%) followed by adults with cancer or lung disease alone or two or more
chronic diseases (55%), adults with cardiovascular disease (46.4%), and adults
with no chronic diseases (43.6%) and diabetes alone (41.4%). Adults with chronic
diseases were also more likely to report use of CAM in the past 12 months (32% to
43.3%), followed by adults with none of these chronic diseases (32%), and adults
with diabetes alone (26.2%). Less than 30% of CAM users in the past 12 months
reported talking to their healthcare professional about CAM use. LIMITATIONS:
Information about CAM use is based on self-report. CONCLUSIONS: Use of CAM,
particularly biologically based CAM therapies, is common and is more likely to be
used by those with chronic diseases.
PMID- 17034288
TI - Effects of contralateral electroacupuncture on brain function: a double-blind,
randomized, pilot clinical trial.
AB - OBJECTIVES: The aim of this study was to ascertain the effects of contralateral
acupuncture on brain function using blind-spot mapping. DESIGN AND PARTICIPANTS:
Forty (40) healthy volunteers in whom the right-side blind spot was larger than
the left-side one-which indicates lower left-brain function-were randomly
assigned into the following two groups in which electroacupuncture was applied
to: (1) the contralateral ST36 acupuncture point (right side), and (2) the
ipsilateral ST36 acupuncture point (left side). OUTCOME MEASURE: Blind-spot
perimetry length was the outcome measure. RESULTS: Electroacupuncture to the
contralateral side decreased the blind-spot perimetry length by 5.0 (-9.3 to 0.9)
[median (interquartile range, IQR)], whereas that to the ipsilateral side
increased the length by 4.5 (-3.7 to 7.8) [median, IQR]. There was significant
difference in this length between the two groups (p < 0.05). CONCLUSIONS: These
results suggest that electroacupuncture application increased or decreased the
brain function- as assessed by changes to the blind spot-depending on the
treatment side: Contralateral-side treatment has a better effect than ipsilateral
side treatment on brain function. However, further randomized studies that
include both right- and left-side-enlarged subjects with a sham needle are needed
to convincingly show the effects of contralateral acupuncture on brain function.
PMID- 17034289
TI - Systematic review of the efficacy of meditation techniques as treatments for
medical illness.
AB - BACKGROUND: Meditative techniques are sought frequently by patients coping with
medical and psychological problems. Because of their increasingly widespread
appeal and use, and the potential for use as medical therapies, a concise and
thorough review of the current state of scientific knowledge of these practices
as medical interventions was conducted. PURPOSE: To systematically review the
evidence supporting efficacy and safety of meditative practices in treating
illnesses, and examine areas warranting further study. Studies on normal healthy
populations are not included. METHODS: Searches were performed using PubMed,
PsycInfo, and the Cochrane Database. Keywords were Meditation, Meditative Prayer,
Yoga, Relaxation Response. Qualifying studies were reviewed and independently
rated based on quality by two reviewers. Mid-to-high-quality studies (those
scoring above 0.65 or 65% on a validated research quality scale) were included.
RESULTS: From a total of 82 identified studies, 20 randomized controlled trials
met our criteria. The studies included 958 subjects total (397 experimentally
treated, 561 controls). No serious adverse events were reported in any of the
included or excluded clinical trials. Serious adverse events are reported in the
medical literature, though rare. The strongest evidence for efficacy was found
for epilepsy, symptoms of the premenstrual syndrome and menopausal symptoms.
Benefit was also demonstrated for mood and anxiety disorders, autoimmune illness,
and emotional disturbance in neoplastic disease. CONCLUSIONS: The results support
the safety and potential efficacy of meditative practices for treating certain
illnesses, particularly in nonpsychotic mood and anxiety disorders. Clear and
reproducible evidence supporting efficacy from large, methodologically sound
studies is lacking.
PMID- 17034294
TI - Vascular endothelial growth factor-D is increased in serum of patients with
lymphangioleiomyomatosis.
AB - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease
characterized by an abnormal proliferation of smooth muscle-like cells (LAM
cells) in the lung and along the axial lymphatics. LAM demonstrates a
heterogeneous clinical course, but there is no serum surrogate marker available
for assessing the disease severity or predicting the disease progression. Since
the authors have recently demonstrated the extensive LAM-associated
lymphangiogenesis and its potential role in progression and metastasis of LAM
cells, they hypothesized that serum levels of lymphangiogenic growth factors
might be increased in LAM and become a surrogate marker for disease severity.
METHODS AND RESULTS: VEGF-A, VEGF-C, and VEGF-D in serum of 44 patients with LAM
were measured by enzyme-linked immunosorbant assay. Only VEGF-D was significantly
increased in LAM patients as compared with age- and gender-matched healthy
volunteers (n=24) (LAM vs. control, geometric mean 95% CI; 1069.3 pg/mL (809.4
approximately 1412.6) vs. 295.9 pg/mL (262.6 approximately 333.5), p<0.0001).
Serum VEGF-D levels negatively correlated with variables of pulmonary function
tests, FEV1/FVC (forced expiratory volume in one second/forced vital capacity)
(r=-0.365, p<0.05) and %DLco/VA (the percentage of diffusing capacity for carbon
monoxide/alveolar volume to the predicted value) (r=-0.560, p<0.001). As
expected, the group who received hormone therapy showed more deteriorated
pulmonary function with higher serum VEGF-D levels than the group who was just
observed without hormone therapy. Immunohistochemical examination of lung
specimens demonstrated the positive immunoreactivity of LAM cells for VEGF-D.
CONCLUSION: Serum VEGF-D levels may be a valuable surrogate marker for evaluating
the disease severity in LAM.
PMID- 17034293
TI - Molecular profile and proliferative responses of rat lymphatic endothelial cells
in culture.
AB - BACKGROUND: Lymphangiogenesis plays an important role in metastasis of many solid
tumors. To study lymphangiogenesis under controlled conditions, an in vitro model
is needed. The goal of this work was to establish such an in vitro model by
determining a molecular profile of rat mesenteric lymphatic endothelial cells
(RMLEC) and characterizing their proliferative responses to angiogenic and
lymphangiogenic factors, such as vascular endothelial growth factor A and C (VEGF
A and VEGF-C). METHODS AND RESULTS: RMLEC strongly expressed most lymphatic
specific markers, including Prox-1, LYVE-1, and VEGFR-3. Proliferation of RMLEC
was serum and heparin dependent. In the presence of low (2%) serum concentration,
exogenously added VEGF-A and VEGFC stimulated RMLEC in a linear and dose
dependent manner. This effect was abrogated by anti-VEGF-A and VEGF-C antibodies,
as well as by soluble Tie-2 and Flt-4 fusion proteins. Abrogation was reversed by
VEGF-A, suggesting that this factor as an important regulator of
lymphangiogenesis. CONCLUSIONS: Cultured RMLEC preserved a molecular profile
consistent with the phenotype of lymphatic endothelium in vivo and respond to
either VEGF-A or VEGF-C factors. VEGFA was able to rescue RMLEC proliferation
inhibited by a neutralizing VEGF-C antibody or soluble Tie-2 fusion protein.
These results support the existence of cross-talk among angiogenic and
lymphangiogenic factors. This work established experimental conditions that allow
in vitro modeling of lymphatic endothelial responses to lymphangiogenic
regulators. Preliminary results using this model suggest that VEGF-A, VEGF-C, and
angiopoietins work in concert to promote lymphangiogenesis in vivo.
PMID- 17034295
TI - Validation of a new technique for the quantitation of edema in the experimental
setting.
AB - BACKGROUND: An inherent limitation to the study of in vivo animal models of
lymphedema is the potential inaccuracy or unreliability of existing methods for
the quantification of edema volume as a surrogate functional measure of lymphatic
transport capacity. Circumference-based techniques have been proposed and
validated as a suitable alternative to volume displacement measurements in human
clinical studies; accordingly, we have elaborated a new application of this
approach that can be applied to small animal studies. METHODS: Acute postsurgical
lymphedema was created experimentally in the murine tail. Both normal and
lymphedematous murine tails were examined. Tail volume was quantitated both by
water displacement and by a digital photographic technique. In selected mice,
after sacrificed on postsurgical day 7, a 6 cm segment was resected from the
midportion of the tail and cauterized to create a closed space. Known incremental
volumes of saline (20-100 microL) were injected for subsequent digital
photographic volumetry. RESULTS: The coefficients of variation for volume
assessment by water displacement and by digital imaging were 0.08+/-0.09 and
0.01+/-0.009, respectively. The two techniques were poorly correlated: while
serial water displacement analysis yielded highly variable measurements within
the same tail, concurrent digital imaging of the tail circumference was quite
reproducible. Furthermore, after parenteral injection of known incremental
volumes of saline, the correlation between the injectate volumes and the
digitally measured increases in volume was high, both in the normal and the
lymphedematous tail. CONCLUSION: In the murine tail, when compared to water
displacement volumetry, digital photography yields highly reproducible data. We
can conclude that the lack of correlation between the two methods, with the
relatively flat slope of the linear regression relationship, reflects inherent
inaccuracies of the water displacement method.
PMID- 17034296
TI - Lymphoscintigraphy to evaluate the effect of high versus low intensity upper body
dynamic exercise on lymphatic function in healthy females.
AB - BACKGROUND: Little is known about the acute effects of exercise on the lymphatic
system. Thus, the purpose was to determine the effect of low versus high
intensity upper body exercise on lymphatic function in healthy females. METHODS
AND RESULTS: On separate days, eight females performed either HI: 12 repeated
sets of arm cranking for 2.5 min at 0.6 W.kg-1, followed by 2.5 min of rest; or
LO: 12 repeated sets of arm cranking for 2.5 min at 0.3 W.kg-1, followed by 2.5
min of rest. One min spot views were taken with a gamma-radiation camera
immediately after injection of 99mTc-antimony colloid and every 10 min thereafter
to measure the clearance rate (CR) from the first and fourth finger-web of each
hand. Radiopharmaceutical uptake in the axillary regions (AX) at 65 min
postinjection was also measured. Clearance from the injection sites was linear
and expressed as a slope (% administered activity.min-1). HI resulted in
significantly greater CR (-0.24%.min-1+/-0.06) than LO (-0.19%.min-1+/-0.05;
p=0.003). A similar trend was seen in AX (HI: 6.3%+/-1.6, LO: 4.8%+/-1.1,
p=0.004). CONCLUSIONS: The results indicate that an arm cranking protocol of
higher intensity is more effective in promoting lymphatic clearance from the
hand. Further, the high intensity protocol may be useful in the functional
evaluation of the lymphatic system in breast cancer survivors and warrants
further investigation.
PMID- 17034297
TI - Literature watch. Emerging roles of the Angiopoietin-Tie and the ephrin-Eph
systems as regulators of cell trafficking.
PMID- 17034300
TI - Generating monodisperse pharmacological aerosols using the spinning-top aerosol
generator.
AB - Pharmacological aerosols of precisely controlled particle size and narrow
dispersity can be generated using the spinning-top aerosol generator (STAG). The
ability of the STAG to generate monodisperse aerosols from solutions of raw drug
compounds makes it a valuable research instrument. In this paper, the versatility
of this instrument has been further demonstrated by aerosolizing a range of
commercially available nebulized pulmonary therapy preparations. Nebules of
Flixotide (fluticasone propionate), Pulmicort (budesonide), Combivent (salbutamol
sulphate and ipratropium bromide), Bricanyl (terbutaline sulphate),
Atrovent(ipratropium bromide), and Salamol (salbutamol sulphate) were each mixed
with ethanol and delivered to the STAG. Monodisperse drug aerosol distributions
were generated with MMADs of 0.95-6.7 microm. To achieve larger particle sizes
from the nebulizer drug suspensions, the STAG formed compound particle
agglomerates derived from the smaller insoluble drug particles. These compound
agglomerates behaved aerodynamically as a single particle, and this was verified
using an aerodynamic particle sizer and an Andersen Cascade Impactor. Scanning
electron microscope images demonstrated their physical structure. On the other
hand using the nebulizer drug solutions, spherical particles proportional to the
original droplet diameter were generated. The aerosols generated by the STAG can
allow investigators to study the scientific principles of inhaled drug deposition
and lung physiology for a range of therapeutic agents.
PMID- 17034301
TI - In vitro validation of 99mTc-HFA-FP delivered via pMDI-spacer.
AB - The purpose of the study was to label Flixotide (fluticasone propionate [FP] with
HFA propellant), with technetium-99m and validate that (99m)Tc acts as a suitable
marker for FP when delivered via pMDI-spacer. Sodium pertechnetate was mixed with
5 mL of butanone. (99m)Tc was extracted into butanone and transferred into an
empty canister. The (99m)Tc lined canister was heated, and the butanone
evaporated to dryness. A supercooled commercial Flixotide canister was decrimped,
and the contents transferred to the (99m)Tc lined canister and recrimped. The
particle size distribution of FP and (99m)Tc from 10 radiolabeled canisters was
measured using an Anderson cascade impactor calibrated to 28.3 L/min, and
compared to commercial FP. The drug (FP) content of each particle size fraction
was measured using ultraviolet spectrophotometry and the (99m)Tc level in each
fraction was measured using an ionization chamber. The percentage of particles in
the fine particle fraction (<;4.7 microm) and the percentage of (99m)Tc from
commercial and radiolabeled canisters were compared. The mean (SD) % FP in the
fine particle fraction, before and after label was 43.2 (1.8) % and 43.9 (2.6) %,
respectively. The mean (SD) % (99m)Tc in the fine particle fraction was 42.1
(5.1) %. The mean %FP exiting spacer at (<4.7 microm) before labeling was not
significantly different from the mean % FP exiting spacer at (<4.7 microm) after
labeling (p > 0.05). The mean % (99m)Tc attached to particles at (<4.7 microm)
after radiolabeling was not significantly different from the mean % FP levels (p
> 0.05). The validation in this study indicates that (99m)Tc can act as a
suitable marker for HFAFP, delivered via pMDI-spacer.
PMID- 17034302
TI - Comparison of SPECT aerosol deposition data with twenty-four-hour clearance
measurements.
AB - Three-dimensional (3D) radionuclide imaging provides detailed information on the
distribution of inhaled aerosol material within the body. Analysis of the data
can provide estimates of the deposition per airway generation. Information on
regional distribution of deposited aerosol can also be obtained from 24-hour
clearance measurements. In this study, a nebulizer was used to deliver a
radiolabeled aerosol to nine human subjects. Single photon emission computed
tomography (SPECT) has been used to assess the distribution of aerosol deposition
per airway generation. The deposition pattern was also estimated using
measurements of the aerosol remaining in the lung 24 h after inhalation. The
error in the SPECT value was assessed by simulation and that in the 24-h
clearance value by repeat analysis. The mean fraction of lung deposition in the
conducting airway (CADF) from SPECT was 0.21. The corresponding 24-h clearance
value was 0.23. These values were not significantly different. There was a weak
but non-significant correlation between the SPECT and 24-h measurements (r =
0.49). The standard error of the difference was 0.11. The corresponding errors on
the SPECT and 24-h clearance measurements were 0.04 and 0.05, respectively. There
was no systematic difference between the values of conducting airways deposition
obtained from 24-h measurements and SPECT. However, there were random differences
on individual subjects, which were larger than the estimated measurement errors.
PMID- 17034303
TI - Comparison of SPECT aerosol deposition data with a human respiratory tract model.
AB - Three-dimensional (3D) radionuclide imaging provides detailed information on the
distribution of inhaled aerosol material within the body. Analysis of the data
can provide estimates of the deposition per airway generation. In this study, two
different nebulizers have been used to deliver radiolabeled aerosols of different
particle size to 12 human subjects. Medical imaging has been used to assess the
deposition in the body. The deposition pattern has also been estimated using the
International Commission on Radiological Protection (ICRP) empirical model and
compared to values obtained by experiment. The results showed generally good
agreement between model and experiment for both aerosols for the deposition in
the extrathoracic and conducting airways. However, there were significant
differences in the fate of the remainder of the aerosol between the amount
deposited in the alveolar region and that exhaled. The inter-subject variability
of deposition predicted by the model was significantly less than that measured,
for all regions of the body. The model predicted quite well the differences in
deposition distribution pattern between the two aerosols. In conclusion, this
study has shown that the ICPR model of inhaled aerosol deposition shows areas of
good agreement with results from experiment. However, there are also areas of
disagreement, which may be explained by hygroscopic particle growth and
individual variation in airway anatomy.
PMID- 17034304
TI - Aerosol deposition in the upper airways of a child.
AB - In a small child, normally only a small amount of inhaled aerosol particles
reaches the lungs because the majority deposits in the upper airways. In this
study, the upper airways of a 9- month-old child, based on computed tomography
(CT) data, are modeled to serve as input for a computational fluid dynamics
package (CFX). Verification of the validity of aerosol deposition calculations by
this package is accomplished by evaluating two test cases, which also can be
solved analytically. The numerically found sedimentation fraction in a
horizontally placed straight pipe shows deviations from the exact solution for
small particle sizes (less than 3 micron) due to small velocities generated by
the use of an unstructured mesh. Although these velocities are small compared to
the mainstream velocity, they are comparable with the terminal settling velocity
of such a particle. Also the test case for inertial impaction in a bend pipe
demonstrated the same problem. With this in mind, the aerosol deposition of 3.7
micron particles in the upper airway model of the child (SAINT-model) was
calculated. Results were compared with experimentally found results in the
literature. For small tidal volumes and flow rates, the computational results
matched the experimentally measured results. However, large deviations were found
for higher flow rates and small particle sizes. Most probably the incompletely
modeled entrance at the nose and inertial effects due to turbulence might be
responsible.
PMID- 17034305
TI - Improving prediction of aerosol deposition in an idealized mouth using large-Eddy
simulation.
AB - Monodisperse aerosol deposition in an idealized mouth geometry with a relatively
small inlet diameter (D (in) = 3.0 mm) was studied numerically using a standard
Large Eddy Simulation (LES). A steady inhalation flow rate of Q = 32.2 L/min was
used. Thousands of particles (2.5, 3.7, and 5.0 microm in diameter and rho (f) =
912.0 kg/m(3) density) were released separately in the computational domain and
aerosol deposition was determined. The total aerosol deposition results in this
idealized mouth were in relatively good agreement when compared with measured
data obtained in separate experiments, showing considerable improvement over the
standard RANS/EIM (Reynolds Averaged Navier-Stokes/Eddy Interaction Model)
approach.
PMID- 17034306
TI - Analysis of particle deposition in the turbinate and olfactory regions using a
human nasal computational fluid dynamics model.
AB - The human nasal passages effectively filter particles from inhaled air. This
prevents harmful pollutants from reaching susceptible pulmonary airways, but may
leave the nasal mucosa vulnerable to potentially injurious effects from inhaled
toxicants. This filtering property may also be strategically used for aerosolized
nasal drug delivery. The nasal route has recently been considered as a means of
delivering systemically acting drugs due to the large absorptive surface area
available in close proximity to the nostrils. In this study, a computational
fluid dynamics (CFD) model of nasal airflow was used with a particle transport
and deposition code to predict localized deposition of inhaled particles in human
nasal passages. The model geometry was formed from MRI scan tracings of the nasal
passages of a healthy adult male. Spherical particles ranging in size from 5 to
50 microm were released from the nostrils. Particle trajectories and deposition
sites were calculated in the presence of steady-state inspiratory airflow at
volumetric flow rates of 7.5, 15, and 30 L/min. The nasal valve, turbinates, and
olfactory region were defined in the CFD model so that particles depositing in
these regions could be identified and correlated with their release positions on
the nostril surfaces. When plotted against impaction parameter, deposition
efficiencies in these regions exhibited maximum values of 53%, 20%, and 3%,
respectively. Analysis of preferential deposition patterns and nostril release
positions under natural breathing scenarios can be used to determine optimal
particle size and flow rate combinations to selectively target drug particles to
specific regions of the nose.
PMID- 17034307
TI - Inhaled particle deposition in unsteady-state respiratory flow at a numerically
constructed model of the human larynx.
AB - To evaluate the clinical effectiveness of aerosol therapy for the lower and upper
respiratory airways, particle deposition at the human laryngeal region has been
analyzed with various unsteady-state respiratory flow-patterns. The flow profiles
and trajectory of aerosol particles were calculated by 3-D thermo-fluid analysis
of a finite volume method (FVM) with 8-CPUs parallel computational system. A
reconstructed physical model of the real laryngeal airways was modified from 3-D
CAM modeling function of Rhinoceros based on the images of Magnetic Resonance
Imaging (MRI). By using 104 MRI images taken vertically and horizontally at
intervals of 2 mm on the oral cavity and the pharynx-larynx respectively, 3-D
physical model of the laryngeal airways was obtained. The numerical results of
flow profile analyzed by the unsteady-state respiration model showed that vortex
flow was occurred with time at near larynx, showing uniform flow profile in both
the oral cavity and upper side of pharynx. The vortex was appeared at the
anterior part of the epiglottis and downward of the vocal cord. However, it was
confirmed that few particles deposit in the vocal cord. In these cases, the
particle deposition was taken place mostly at the oral cavity and the oropharynx.
On the other hand, the relationship between the particle deposition efficiency
and the impaction in the laryngeal region was well agreement with the data sets
of ICRP task group (1993) for the larynx deposition.
PMID- 17034308
TI - Characterization of regional and local deposition of inhaled aerosol drugs in the
respiratory system by computational fluid and particle dynamics methods.
AB - The present work describes the local deposition patterns of therapeutic aerosols
in the oropharyngeal airways, healthy and diseased bronchi and alveoli using
computational fluid and particle dynamics techniques. A user-enhanced
computational fluid dynamics commercial finite- volume software package was used
to compute airflow fields, deposition efficiencies, and deposition patterns of
therapeutic aerosols along the airways. Adequate numerical meshes, generated in
different airway sections, enabled us to more precisely define trajectories and
local deposition patterns of inhaled particles than before. Deposition patterns
show a high degree of heterogeneity of deposition along the airways, being more
uniform for nanoparticles compared to micro-particles in the whole respiratory
system at all inspiratory flow rates. Extrathoracic and tracheobronchial
deposition fractions of nanoparticles decrease with increasing flow rates.
However, vice versa happens to the micron-size particles, that is, the deposition
fraction is higher at high flow rates. Both airway constrictions and the presence
of tumors significantly increased the deposition efficiencies compared to the
deposition efficiencies in healthy airways by a factor ranging from 1.2 to 4.4.
In alveoli, the deposition patterns are strongly influenced by particle size and
direction of gravity. This study demonstrated that numerical modeling can be a
powerful tool in the aerosol drug delivery optimization. Present results may be
integrated in future aerosol drug therapy protocols.
PMID- 17034309
TI - Three-dimensional computational fluid dynamics simulations of particle deposition
in the tracheobronchial tree.
AB - Simulation of the dynamics and disposition of inhaled particles within human
lungs is an invaluable tool in both the development of inhaled pharmacologic
drugs and the risk assessment of environmental particulate matter (PM). The goal
of the present focused study was to assess the utility of three-dimensional
computational fluid dynamics (CFD) models in studying the local deposition
patterns of PM in respiratory airways. CFD models were validated using data from
published experimental studies in human lung casts. The ability of CFD to
appropriately simulate trends in deposition patterns due to changing ventilatory
conditions was specifically addressed. CFD simulations of airflow and particle
motion were performed in a model of the trachea and main bronchi using Fluent
Inc.'s FIDAP CFD software. Particle diameters of 8 microm were considered for
input flow rates of 15 and 60 L/min. CFD was able to reproduce the observed
spatial heterogeneities of deposition within the modeled bifurcations, and
correctly predicted the "hot-spots" of particle deposition on carinal ridges. The
CFD methods also predicted observed differences in deposition for high-versus-low
flow rates. CFD models may provide an efficient means of studying the complex
effects of airway geometry, particle characteristics, and ventilatory parameters
on particle deposition and therefore aid in the design of human subject
experiments.
PMID- 17034310
TI - Comparison of pharmacokinetics and vasodilatory effect of nebulized and infused
iloprost in experimental pulmonary hypertension: rapid tolerance development.
AB - Aerosolized iloprost has been suggested for selective pulmonary vasodilatation in
severe pulmonary hypertension, but its pharmacokinetic profile is largely
unknown. In perfused rabbit lungs, continuous infusion of the thromboxane mimetic
U46619 was employed for establishing stable pulmonary hypertension. Delivery of a
total amount of 75, 300, and 900 ng of iloprost to the bronchoalveolar space by a
10 min-aerosolization maneuver caused a dose-dependent pulmonary vasodilatation.
Similarly, dose-dependent appearance of iloprost in the recirculating perfusate
was noted, with maximum intravascular concentrations of iloprost ranging at 140,
510, and 1163 pg/mL at the same time period. Comparing pharmacokinetics and
pharmacodynamics in a more detailed fashion, the following aspects were of
interest. (i) The bioavailability (i.e., the percentage of aerosolized iloprost
appearing intravascularly) decreased from 76% at the lowest to 33% at the highest
iloprost dosage. (ii) The pulmonary vasodilatory response commenced already
during the nebulization maneuver and preceded the perfusate entry of iloprost.
(iii) After 3-3.5 h, the pulmonary vasodilatory response to aerosolized iloprost
had virtually completely leveled off, whereas approximately two-thirds of the
maximum iloprost perfusate levels were still detectable. A corresponding loss of
vasodilatory response was also noted in experiments with continuous iloprost
perfusion for clamping of the intravascular concentration of this prostanoid. We
conclude that aerosolized iloprost causes dose-dependent vasodilatation and
iloprost entry into the vascular space in a pulmonary hypertension model. Limited
bioavailability in the higher dose range may suggest active prostanoid transport
processes, and the early pulmonary vasodilatory response appears to be
independent of prostanoid entry into the vessel lumen. Surprisingly, rapid
tolerance development to the vasodilatory effect of iloprost is noted, occurring
even with fully maintained perfusate levels of this agent.
PMID- 17034311
TI - Peak inspiratory flow rate after methacholine challenge in asthmatic patients and
its impact on the effect of formoterol via different inhalers.
AB - The goal of the present study was to investigate the bronchodilating effects of 6
and 12 microg formoterol delivered by the Turbuhaler, in comparison to salbutamol
200 microg (metered dose inhaler) and to controls without treatment. After
inducing acute and severe bronchial obstruction by means of methacholine
challenge, peak inspiratory mouth flow (PIMF) was measured through a stenosis,
simulating the internal resistance of the Turbuhaler, with the in-check device.
In addition the relationship was studied between PIMF and clinical response in
the 3 treatment groups. In the 176 patients methacholine caused a mean fall in
FEV(1) of 37.1 +/- 6.9% compared to baseline. Ten minutes after bronchodilator
inhalation, FEV(1) improved significantly in all three treatment groups. At 30
minutes after bronchodilator administration, only the salbutamol 200 microg and
the formoterol 12 microg groups had a significantly greater increase in FEV1 than
controls (0.69 +/- 0.43 l and 0.66 +/- 0.37 l vs 0.38 +/- 0.32 l, p < 0.0005),
whereas the formoterol 6 microg group showed no significant improvement (0.41 +/-
0.38 l, p = 0.74). Thirteen patients (7.4%) did not reach a minimal PIMF of 30
l/min through the in-check device after challenge. In the four patients in the
formoterol 6 microg group with a PIMF below 30 l/min inhalation did not cause
bronchodilation. In conclusion, the results demonstrate that 6 microg formoterol
via Turbuhaler leads to less and slower onset of bronchodilation compared to the
other groups in our setting. If patients fail to generate a PIMF of 30 l/min, 6
microg formoterol via Turbuhaler may provide inadequate relief in a severe asthma
attack.
PMID- 17034312
TI - Rationale for the selection of an aerosol delivery system for gene delivery.
AB - Genetic therapeutics show great promise toward the treatment of illnesses
associated with the lungs; however, current methods of delivery such as jet and
ultrasonic nebulization decrease the activity and effectiveness of these
treatments. Extremely low transfection rates exhibited by non-complexed plasmid
DNA in these nebulizers have been primarily attributed to poor translocation and
loss of molecular integrity as a consequence of shear-induced degradation.
Current research focusing on methods to increase transfection rates via the
pulmonary delivery route has largely concentrated on the incorporation of carbon
dioxide in the air stream to increase breath depth as well as the addition of
cationic agents that condense DNA into compact, ordered complexes. The purpose of
this study was to examine the impact of several classic as well as the latest
atomization devices on the structure of non-complexed DNA. Various sizes of
plasmid and cosmid DNA were processed through an electrostatic spray, ultrasonic
nebulizer, vibrating mesh nebulizer, and jet nebulizer. Results varied
dramatically based upon atomization device as well as DNA size. This may explain
the inefficiency experienced by genetic therapeutics during pulmonary delivery.
More importantly, this suggests that the selection of an atomization device
should consider DNA size in order to achieve optimal gene delivery to the lungs.
PMID- 17034313
TI - Assessing a system to capture stray aerosol during inhalation of nebulized
liposomal cisplatin.
AB - The aim of this study was to determine the efficacy of using a high-efficiency
particulate air (HEPA) filter air cleaning system, a demistifier, to reduce the
potential risk of fugitive aerosol contact in health care personnel working with
patients inhaling nebulized liposomal encapsulated SLIT (Sustained-release Lipid
Inhalation Targeting) Cisplatin. Filters were used to sample platinum in the air
outside the tent and from the tent's exhaust stream. Air collection was performed
under three conditions: (1) during patient dosing (14 h of air collection); (2)
immediately after the patient has left the demistifier tent (4 h of air
collection); and (3) when 7 mL of drug product was nebulized to dryness in the
tent without a patient being present. Filters were collected, and placed in an
extraction solvent. Subsequently, the solvent was assayed for platinum content by
inductively coupled plasma-mass spectrometry (ICP-MS). Platinum levels in the
extraction solvent were indistinguishable from the blank controls for all
conditions. Measured levels were below workplace exposure limits established for
cisplatin by the Occupational Safety and Health Administration (i.e., 2 ng .
(L(1)). In addition, the demistifier was able to effectively capture aerosolized
SLIT Cisplatin following nebulization of 7 mL of drug product to dryness in the
tent. The demistifier tent is effective at containing any nebulized liposomal
encapsulated cisplatin during patient treatment. Importantly, because the tent's
HEPA filtration system is effective at removing any nebulized liposomal
cisplatin, the exhausted air, which is free of platinum, can be returned into the
room with no additional ventilation precautions.
PMID- 17034314
TI - An optimized in vitro model of the respiratory tract wall to study particle cell
interactions.
AB - As a part of the respiratory tissue barrier, lung epithelial cells play an
important role against the penetration of the body by inhaled particulate foreign
materials. In most cell culture models, which are designed to study particle-cell
interactions, the cells are immersed in medium. This does not reflect the
physiological condition of lung epithelial cells which are exposed to air,
separated from it only by a very thin liquid lining layer with a surfactant film
at the air-liquid interface. In this study, A549 epithelial cells were grown on
microporous membranes in a two chamber system. After the formation of a confluent
monolayer the cells were exposed to air. The morphology of the cells and the
expression of tight junction proteins were studied with confocal laser scanning
and transmission electron microscopy. Air-exposed cells maintained monolayer
structure for 2 days, expressed tight junctions and developed transepithelial
electrical resistance. Surfactant was produced and released at the apical side of
the air-exposed epithelial cells. In order to study particle-cell interactions
fluorescent 1 microm polystyrene particles were sprayed over the epithelial
surface. After 4 h, 8.8% of particles were found inside the epithelium. This
fraction increased to 38% after 24 h. During all observations, particles were
always found in the cells but never between them. In this study, we present an in
vitro model of the respiratory tract wall consisting of air-exposed lung
epithelial cells covered by a liquid lining layer with a surfactant film to study
particle-cell interactions.
PMID- 17034315
TI - Advances in our understanding of aerosolized iloprost for pulmonary hypertension.
PMID- 17034316
TI - Assessment of emotional reactivity produced by exposure to virtual environments
in patients with eating disorders.
AB - The aim of this study was to assess the usefulness of virtual environments
representing situations that are emotionally significant to subjects with eating
disorders (ED). These environments may be applied with both evaluative and
therapeutic aims and in simulation procedures to carry out a range of
experimental studies. This paper is part of a wider research project analyzing
the influence of the situation to which subjects are exposed on their performance
on body image estimation tasks. Thirty female patients with eating disorders were
exposed to six virtual environments: a living-room (neutral situation), a kitchen
with high-calorie food, a kitchen with low-calorie food, a restaurant with high
calorie food, a restaurant with low-calorie food, and a swimming-pool. After
exposure to each environment the STAI-S (a measurement of state anxiety) and the
CDB (a measurement of depression) were administered to all subjects. The results
show that virtual reality instruments are particularly useful for simulating
everyday situations that may provoke emotional reactions such as anxiety and
depression, in patients with ED. Virtual environments in which subjects are
obliged to ingest high-calorie food provoke the highest levels of state anxiety
and depression.
PMID- 17034317
TI - Demographic, habitual, and socioeconomic determinants of Internet addiction
disorder: an empirical study of Korean teenagers.
AB - The objective of this study was to analyze the demographic, socioeconomic, and
habitual causes of juvenile Internet addiction. All do not agree that Internet
addiction disorder (IAD) is a new type of addiction, but they agree that the IAD
phenomenon has widely spread over recent years. This is also true in Korea. For
this study, six schools in Korea were selected to collect data: two from Seoul,
two from suburban areas, and two from rural areas. Two hundred and forty copies
were collected out of some 700 copies distributed. Multiple regression models
were employed to explore significant predictors of IAD. This study showed that at
least two out of 100 teenagers in Korea are seriously suffering from IAD and that
approximately one out of two is exposed to a kind of IAD. The causes of IAD are
not only associated with habitual backgrounds for use of the Internet, but also
demographic and socioeconomic backgrounds. Therefore, it can be said that the
development of IAD is an interactive process between juveniles' habits of using
Internet, and their demographic and socioeconomic backgrounds. As IAD progresses,
a single type of intervention such as parent interventions or school
interventions does not work effectively. Multimodal interventions are required to
provide counseling services for individuals suffering from IAD.
PMID- 17034318
TI - Characteristics and motives of adolescents talking with strangers on the
internet.
AB - Despite widespread concerns about the dangers of adolescents' online
communication with strangers, we know little about (a) which types of adolescents
talk with strangers and (b) what motivates them to do so. Drawing on a survey
among 412 Dutch adolescents, we found that early adolescents (12-14-year-olds)
were most prone to talk with strangers on the internet. If adolescents
communicated online more frequently, they less often talked with strangers on the
internet. However, if adolescents engaged in long chat sessions, they tended to
talk with strangers on the internet more often. In contrast to earlier research,
introversion was not related to adolescents' tendency to talk with strangers. The
motives of entertainment, meeting new people, and social compensation increased
adolescents' online communication with strangers.
PMID- 17034319
TI - Pilot study for assessing the behaviors of patients with schizophrenia towards a
virtual avatar.
AB - This study examined whether a virtual avatar could be perceived as a real human
by patients with mental disease, especially schizophrenia, as well as whether a
virtual avatar could be applied to acquiring patients' behavior characteristics
in a short conversation situation. The virtual avatar has been used for various
applications which need to communicate with other person or to train or educate
by showing humanlike behavior. Recently, many researches have shown that the
virtual avatar technology has been enhanced and the avatar could be perceived
like real human. A virtual avatar, standing in a virtual room, was designed for
this study. Tasks to approach, initiate a talk, and answer to avatar's questions
was assigned to the 11 patients with schizophrenia. As behavioral parameters in
the virtual environment, the interpersonal distance and the verbal response time
were acquired. In addition, the Positive and Negative Syndrome Scale (PANSS) for
patients was administered in order to investigate the relationship between
patients' symptomatic characteristics and behavior parameters. The interpersonal
distance was negatively correlated with the negative syndrome scale, a subscale
of PANSS, which is consistent with previous research reporting the relationship
between interpersonal distance and a real person's image. The verbal response
time, however, was not correlated with any other subscale of PANSS. After
analyzing subitems of the negative syndrome of PANSS, two positive correlations
were found: one was with blunted affect and the other was with poor rapport. We
concluded that the virtual avatar could be perceived as a real human by
schizophrenic patients and the avatar could draw the schizophrenic patients'
behavior characteristics.
PMID- 17034320
TI - Understanding behavioral intention to participate in virtual communities.
AB - Virtual communities are formed on the Internet and are expected to serve the
needs of members for communication, information, and entertainment. Online
businesses should consider virtual communities as a new market place since their
members are current or future customers. Thus, there is a need to understand the
determinants of member intentions to participate in virtual communities. Based on
the extended theory of planned behavior (TPB), this study develop a research
model to identify the attitudinal, social, and perceived behavioral control
factors that would influence members intentions to participate in virtual
communities. Specifically, the research model decomposes the attitude component
into perceived usefulness, perceived ease of use and perceived trust, and the
perceived behavioral control component into Internet self-efficacy and
facilitating conditions. Based on a survey of 165 community members, this study
uses structural equation modeling (SEM) approach to investigate the research
model. The results indicate that attitude and perceived behavioral control
significantly influence member behavioral intentions, while subjective norms do
not. Finally, this study discusses the implications of these findings and offer
directions for future research.
PMID- 17034321
TI - Internet access and use among homeless and indigent drug users in Long Beach,
California.
AB - There has been a growing interest in using the Internet to access a variety of
populations for prevention education and health care. It is not clear that this
is viable for homeless and other marginalized populations. The purpose of this
study was to describe Internet access and use among a sample of homeless and
indigent drug users. A brief questionnaire was developed to assess computer
ownership, use, email, and Internet access and use. Participants were recruited
through a community-based human immunodeficiency virus (HIV) prevention program.
265 participants completed the questionnaire. While 55% had ever used a computer
in their lifetime, only 25% had ever owned a computer, 24% had ever had their own
email account, 33% had access to a working computer in the last 30 days, 10% had
sent or received email in the last 30 days, and 19% had surfed or accessed
information on the Internet in the last 30 days. Logistic regression predicting
lifetime use of a computer showed predictive factors of having completed high
school (Odds Ratio [OR] = 4.5; 95% Confidence Interval [CI] = 2.41, 8.38) and
number of days used amphetamines in the last 30 days, per 5 days of use (OR =
1.64; 95% CI = 1.18, 2.27). Inversely related were age, per 5 years of age (OR =
0.78; 95% CI = 0.65, 0.93) and number of days used marijuana in the last 30 days,
per 5 days of use (OR = 0.97; 95% CI = 0.76, 0.99). Very low access and usage
suggest that Internet-based public health education models be reexamined for this
population. The association with amphetamine use may indicate a facilitating
effect of amphetamine by heightening awareness and increasing wakefulness.
PMID- 17034322
TI - Using instant messaging for Internet-based interviews.
AB - One method of data collection that has rarely been applied online is the one-on
one interview. Because of its widespread use, the Internet-based service instant
messaging (IM) seems to be suitable to conduct scientific online interviews. A
unique benefit of IM is the existence of public address books. These can be used
both as a sampling frame and as a cross-reference to validate respondents'
demographic data. The feasibility of IM interviews was examined in a WWW survey
as well as in actual IM interviews that were combined with an experimental
manipulation of the request for participation. On the basis of self-reports,
respondent behavior, and data in the address books, the studies have demonstrated
that the risk of receiving false data in IM interviews is small. Not only is the
quality of the obtainable data satisfying but the contact rate, response rate,
and retention rate as well. Moreover, the experimental test demonstrated that the
response rate is influenced by the information provided in the chat request. On
the basis of the study results, recommendations are given as to when and how IM
interviews should be used as a data collection method.
PMID- 17034323
TI - Sharing tips with strangers: exploiting gift culture in computer gaming.
AB - The aim of this study was to look at motivations behind altruistic behavior in
virtual communities by studying the sharing of game tips by experienced gamers.
We examine several possible motivations (pure altruism, generalized reciprocity,
and reputation) and qualitatively analyze tip types in terms of usefulness,
visibility, and skill level. We found that in games that do not support a
"performance stage" for skill demonstration, players often share game tips as a
strategy to attract attention. To a certain degree, reciprocity can be used to
explain small favor exchanges, but earning social reputation is often a much
stronger motivating factor.
PMID- 17034324
TI - Identity and intimacy crises and their relationship to internet dependence among
college students.
AB - In an attempt to test Kandell's proposition that internet dependents used the
internet as a coping mechanism against underlying psychological issues, this
study investigated the extent to which the fifth and sixth Eriksonian crises
(identity, intimacy), were related to internet dependence (online chatting,
gaming) among college students. Students spending more than 10 hours per week on
chatting/gaming were classified as dependents. On the basis of a national sample
of freshmen in Taiwan, this study found that the dependents scored significantly
lower on most of the measures that reflected the successful resolution of the
crises, and higher on the measures that reflected unsuccessful resolution of the
crises. Kandell's proposition was supported.
PMID- 17034325
TI - Personality traits as predictors of intentions to seek online information about
STDs and HIV/AIDS among junior and senior college students in Taiwan.
AB - The purpose of this cross-sectional study is to examine how personality traits
such as sensation- seeking and impulsive decision-making affect Taiwanese college
students' intentions to seek online information about sexually transmitted
diseases (STDs) and human immunodeficiency virus/acquired immune deficiency
syndrome (HIV/AIDS). Five hundred thirty-five (n = 535) junior and senior college
students in Taiwan were recruited and completed self-report questionnaires. This
study found high sensation-seekers were more likely to seek information about
STDs and HIV/AIDS on the Internet than low sensation-seekers. Impulsive decision
makers were less likely than rational decision-makers to seek information about
STDs and HIV/AIDS on the Internet. These findings suggest that personality needs
to be considered as an exploratory factor which potentially influences intentions
to seek STD and HIV/AIDS information on the Internet among Taiwanese college
students.
PMID- 17034326
TI - Friend networking sites and their relationship to adolescents' well-being and
social self-esteem.
AB - The aim of this study was to investigate the consequences of friend networking
sites (e.g., Friendster, MySpace) for adolescents' self-esteem and well-being. We
conducted a survey among 881 adolescents (10-19-year-olds) who had an online
profile on a Dutch friend networking site. Using structural equation modeling, we
found that the frequency with which adolescents used the site had an indirect
effect on their social self-esteem and well-being. The use of the friend
networking site stimulated the number of relationships formed on the site, the
frequency with which adolescents received feedback on their profiles, and the
tone (i.e., positive vs. negative) of this feedback. Positive feedback on the
profiles enhanced adolescents' social self-esteem and well-being, whereas
negative feedback decreased their self-esteem and well-being.
PMID- 17034327
TI - Head-mounted displays for clinical virtual reality applications: pitfalls in
understanding user behavior while using technology.
AB - The use of virtual environments with head-mounted displays (HMDs) offers unique
assets to the evaluation and therapy of clinical populations. However, research
examining the effects of this technology on clinical populations is sparse.
Understanding how wearers interact with the HMD is vital. Discomfort leads to
altered use of the HMD that could confound performance measures; the very
measures which might be used as tools for clinical decision making. The current
study is a post-hoc analysis of the relationship between HMD use and HMD comfort.
The analysis was conducted to examine contributing factors for a high incidence
of simulator sickness observed in an HMD-based driving simulator. Pearson
correlation analysis was used to evaluate objective and subjective measures of
HMD performance and self-reported user comfort ratings. The results indicated
weak correlations between these variables, indicating the complexity of
quantifying user discomfort and HMD performance. Comparison of two case studies
detailing user behavior in the virtual environment demonstrates that selected
variables may not capture how individuals use the HMD. The validity and
usefulness of the HMD-based virtual environments must be understood to fully reap
the benefits of virtual reality (VR) in rehabilitation medicine.
PMID- 17034328
TI - Effects of a personified guide on adherence to an online program for alcohol
abusers.
AB - The quality of the therapeutic alliance has robust effects on the outcome of
psychotherapy and psychopharmacologic interventions. Automated behavioral health
programs that are being developed to increase access to mental health treatment
are administered in the absence of direct human participation, thereby precluding
the development of a traditional therapeutic relationship. The aim of this study
was to develop a personified guide designed to stimulate reactions similar to
those experienced in a therapeutic relationship, and evaluate the effect of the
guide on adherence to and satisfaction with an online alcohol use evaluation
program. After completing a battery of four standard questionnaires used to
evaluate problem drinking, 288 subjects were randomized to receive feedback on
their results in text form or via a multimedia condition involving a personified
guide. Those who received feedback via the guide demonstrated greater levels of
program adherence by completing more modules. Reported satisfactions levels did
not differ between the two conditions. Encouraging the personification of an
automated behavioral health intervention may lead to greater levels of engagement
with the program.
PMID- 17034329
TI - Systematic evaluation of current control devices used by people with intellectual
disabilities in non-immersive virtual environments.
AB - Virtual environments have a role to play in facilitating the acquisition of
living skills in people with intellectual disabilities, improving their cognitive
skills and providing them with entertainment. However, the currently recommended
devices to allow navigation in and interaction with the environments are
difficult to use. Using a methodology established in an earlier study, the study
aims to systematically document the performance of users with the currently
recommended devices in order to (i) inform the design of a usable control device
or devices and (ii) act as a baseline against which they can be evaluated. 40
people with severe intellectual disabilities aged 21-67 years used four
environments with an equal number of sessions with the different devices being
evaluated. Results indicate that when forward movement is provided by the
software using the mouse for both navigation and interaction allows better
performance both initially and after exposure than using the fire button on the
joystick. When the user had to initiate forward movement with the navigation
device, the joystick allowed better performance than the arrows on the keyboard.
Preventing slippage of the joystick base would make its use much easier and it is
suggested that separate devices are retained for navigation and interaction.
PMID- 17034330
TI - Sexual strategies theory and Internet personal advertisements.
AB - Sexual Strategies Theory supposes that certain characteristics--namely, physical
attractiveness in women and dominance and the ability to provide material
resources in men--are highly desirable to potential mates because they are
evolutionarily advantageous. However, socially based characteristics (e.g.,
positive personality traits, common interests) are also desirable in potential
mates. It was predicted that people who are weaker on evolutionarily advantageous
traits (i.e., less attractive women, less wealthy men) would emphasize
alternative, socially desirable traits to compensate for these perceived
deficiencies. One hundred fifty-one Internet personal advertisements were
analyzed for attractiveness, income, mention of physical attributes, and mention
of other positive personal characteristics. Results were generally consistent
with predictions. In males, both wealth and attractiveness were related to
decreased emphasis on other positive personal characteristics, while in women,
emphasis on physical attributes (but not objectively rated physical
attractiveness) was negatively related to emphasis on other positive personal
characteristics.
PMID- 17034331
TI - Internet communication: an activity that appeals to shy and socially phobic
people?
AB - Shyness (or social anxiety) and social phobia can be viewed as two distinct
conditions, and this study investigates whether they are related to use of the
Internet generally, and for communication purposes. 362 participants from two
schools, a college and a university in the Teesside area in England were asked to
complete Mattick and Clarke's (1998) Social Phobia (SPS) and Social Interaction
Anxiety (SIAS) scales and also answer a questionnaire which asked them about
their use of the Internet generally and for communication purposes. The findings
from these suggested that social anxiety and social phobia are not highly
associated with use of the Internet either in general, or for communication
purposes, although minor associations with certain aspects of Internet use are
discussed.
PMID- 17034332
TI - Success factors in internet-based psychological counseling.
AB - A number of special effectiveness factors of internet counseling are described,
which represent advantages over face-to-face counseling. These factors were
explored in a large-scale internet counseling project that ran for several years.
PMID- 17034333
TI - An experimental study on fear of public speaking using a virtual environment.
AB - This paper examines a necessary condition for successful exploitation of a
virtual environment (VE) in therapeutic intervention for fear of public speaking.
The condition is that clients experience a degree of anxiety in the VE that is
similar to what they would have been expected to experience in a similar real
world setting. We refer to this as a "presence" response. The experimental study
involved 20 people who were confident public speakers and 16 who were phobic,
assessed on a standard psychological scale. Half of each group spoke within a VE
depicting an empty seminar room, and the other half within the same room but
populated by a neutrally behaving virtual audience of five people. Three
responses were measured--a questionnaire-based measure of anxiety, a measure of
self-focused attention on somatic responses, and actual heart rate. On all
responses, the people with phobia showed a significant increase in signs of
anxiety when speaking to the virtual audience compared to the empty room, whereas
the confident people did not. The result was strong in spite of the relatively
low representational and behavioral fidelity of the virtual characters.
PMID- 17034334
TI - Impulsive nonconformity in female chat room users.
AB - Heavy chat room use has been associated with social isolation, introversion,
impulse control problems, and risk taking. Such characteristics form part of the
cluster of traits associated with schizotypy. This study used multiple regression
to examine the relationship between age, sex, four dimensions of schizotypy, and
frequency of reported chat room use. The only significant association with
schizotypy was between frequency of chat room use and impulsive nonconformity
(IN) in females. These findings may be explained by the increased risk associated
with female chat room use.
PMID- 17034335
TI - The appeal of violent video games to lower educated aggressive adolescent boys
from two countries.
AB - The objective of this study was to test the effect of individual differences on
appeal and use of video games. Participants were 299 adolescent boys from lower
and higher secondary schools in the Netherlands and Belgium. In general, boys
were most attracted to violent video games. Boys that scored higher in trait
aggressiveness and lower in empathy were especially attracted to violent games
and spent more time playing video games than did boys lower in trait
aggressiveness. Lower educated boys showed more appreciation for both violent and
nonviolent games and spent more time playing them than did higher educated boys.
The present study showed that aggressive and less empathic boys were most
attracted to violent games. The fact that heavy users of violent games show less
empathy and higher aggressiveness suggests the possibility of desensitization.
Other studies have shown that playing violent games increases aggressiveness and
decreases empathy. These results combined suggest the possibility of a violence
cycle. Aggressive individuals are attracted to violent games. Playing violent
games increases aggressiveness and decreases empathy, which in turn leads to
increased appreciation and use of violent games.
PMID- 17034338
TI - Protein-folding dynamics: overview of molecular simulation techniques.
AB - Molecular dynamics (MD) is an invaluable tool with which to study protein folding
in silico. Although just a few years ago the dynamic behavior of a protein
molecule could be simulated only in the neighborhood of the experimental
conformation (or protein unfolding could be simulated at high temperature), the
advent of distributed computing, new techniques such as replica-exchange MD, new
approaches (based on, e.g., the stochastic difference equation), and physics
based reduced models of proteins now make it possible to study protein-folding
pathways from completely unfolded structures. In this review, we present
algorithms for MD and their extensions and applications to protein-folding
studies, using all-atom models with explicit and implicit solvent as well as
reduced models of polypeptide chains.
PMID- 17034339
TI - A spectroscopist's view of energy states, energy transfers, and chemical
reactions.
AB - This chapter describes a research career beginning at Berkeley in 1960, shortly
after Sputnik and the invention of the laser. Following thesis work on
vibrational spectroscopy and the chemical reactivity of small molecules, we
studied vibrational energy transfers in my own lab. Collision-induced transfers
among vibrations of a single molecule, from one molecule to another, and from
vibration to rotation and translation were elucidated. My research group also
studied the competition between vibrational relaxation and chemical reaction for
potentially reactive collisions with one molecule vibrationally excited. Lasers
were used to enrich isotopes by the excitation of a predissociative transition of
a selected isotopomer. We also tested the hypotheses of transition-state theory
for unimolecular reactions of ketene, formaldehyde, and formyl fluoride by (a)
resolving individual molecular eigenstates above a dissociation threshold, (b)
locating vibrational levels at the transition state, (c) observing quantum
resonances in the barrier region for motion along a reaction coordinate, and (d)
studying energy release to fragments.
PMID- 17034340
TI - The mechanistic basis of infarct healing.
AB - Myocardial infarction triggers an inflammatory cascade that results in healing
and replacement of the damaged tissue with scar. Cardiomyocyte necrosis triggers
innate immune mechanisms eliciting Toll-like receptor- mediated responses,
activating the complement cascade and generating reactive oxygen species.
Subsequent activation of NF-kappaB is a critical element in the regulation of
cytokine, chemokine, and adhesion molecule expression in the ischemic myocardium.
Chemokine induction mediates leukocyte recruitment in the myocardium. Pleiotropic
proinflammatory cytokines, such as TNF-alpha, IL-1, and IL-6, are also
upregulated in the infarct and exert a wide range of effects on a variety of cell
types. Timely repression of proinflammatory gene synthesis is crucial for optimal
healing; IL-10 and TGF-beta-mediated pathways may be important for suppression of
chemokine and cytokine expression and for resolution of the leukocytic
infiltrate. In addition, TGF-beta may be critically involved in inducing
myofibroblast differentiation and activation, promoting extracellular matrix
protein deposition in the infarcted area. The composition of the extracellular
matrix plays an important role in regulating cell behavior. Both structural and
matricellular proteins modulate cell signaling through interactions with specific
surface receptors. The molecular and cellular changes associated with infarct
healing directly influence ventricular remodeling and affect prognosis in
patients with myocardial infarction.
PMID- 17034341
TI - Redox control of neural function: background, mechanisms, and significance.
AB - The redox environment within neural cells is dependent on a series of redox
couples. The glutathione disulfide/ glutathione (GSSG/GSH) redox pair forms the
major redox couple in cells and as such plays a critical role in regulating redox
dependent cellular functions. Not only does GSH act as an antioxidant but it also
can modulate the activity of a variety of different proteins via S
glutathionylation of cysteine sulfhydryl groups. The thioredoxin system also
makes a significant contribution to the redox environment by reducing inter- and
intrachain protein disulfide bonds as well as maintaining the activity of
important antioxidant enzymes such as peroxiredoxins and methionine sulfoxide
reductases. The redox environment affects the activity and function of a number
of different protein phosphatases, protein kinases, and transcription factors.
The sum of these effects will determine how changes in the redox environment
alter overall cellular function, thereby playing a fundamental role in regulating
neural cell fate and physiology.
PMID- 17034342
TI - Oxidative stress in neurodegenerative disorders.
PMID- 17034343
TI - Nitrosative stress, cellular stress response, and thiol homeostasis in patients
with Alzheimer's disease.
AB - Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive and
memory decline, personality changes, and synapse loss. Increasing evidence
indicates that factors such as oxidative and nitrosative stress, glutathione
depletion, and impaired protein metabolism can interact in a vicious cycle, which
is central to AD pathogenesis. In the present study, we demonstrate that brains
of AD patients undergo oxidative changes classically associated with a strong
induction of the so-called vitagenes, including the heat shock proteins (HSPs)
heme oxygenase-1 (HO-1), HSP60, and HSP72, as well as thioredoxin reductase
(TRXr). In inferior parietal brain of AD patients, a significant increase in the
expression of HO-1 and TRXr was observed, whereas HO-2 expression was decreased,
compared with controls. TRHr was not increased in AD cerebellum. Plasma GSH was
decreased in AD patients, compared with the control group, and was associated
with a significant increase in oxidative stress markers (i.e., GSSG,
hydroxynonenal, protein carbonyl content, and nitrotyrosine). In AD lymphocytes,
we observed an increased expression of inducible nitric oxide synthase, HO-1,
Hsp72, HSP60, and TRXr. Our data support a role for nitrative stress in the
pathogenesis of AD and indicate that the stress-responsive genes, such as HO-1
and TRXr, may represent important targets for novel cytoprotective strategies.
PMID- 17034344
TI - Experimental encephalomyelitis induces changes in DJ-1: implications for
oxidative stress in multiple sclerosis.
AB - DJ-1 plays an important role in oxidative stress, and is involved in various
neurodegenerative diseases. Accumulating evidence suggests a central role for
oxidative stress in multiple sclerosis (MS). The aim of this study was to examine
whether changes occur in DJ-1 expression in an animal model of MS, experimental
autoimmune encephalomyelitis (EAE). We found upregulation of DJ-1 mRNA and
protein expression levels in EAE and a correlation between disease severity and
increased DJ-1 levels. Although DJ-1 isoforms were more alkaline in controls, in
EAE, a shift was noted toward acidic isoforms. ROS induced by SIN-I exposure led
to an increase in DJ-1 mRNA and protein levels in human glioma U-87 cells.
Immunocytochemical staining demonstrated that DJ-1 is present both in the
cytoplasm and the nuclei of these cells. This is the first report of modulation
of DJ-1 expression in EAE. Upregulation of DJ-1 was noted in EAE, and similar
results were observed in glioma cells exposed to ROS. In view of the accumulating
evidence on the central role of oxidative stress in MS, and the importance of DJ
1 in oxidative stress management by the CNS, we believe that DJ-1 will be found
to have a central role in MS.
PMID- 17034345
TI - Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders.
AB - When subjected to excessive oxidative stress, neurons may respond adaptively to
overcome the stress, or they may activate a programmed cell death pathway called
apoptosis. Apoptosis is characterized by alterations in mitochondria and the
endoplasmic reticulum and activation of cysteine proteases called caspases.
Increasing evidence suggests that apoptotic biochemical cascades are involved in
the dysfunction and death of neurons in neurodegenerative disorders such as
Alzheimer's, Parkinson, and Huntington's diseases. Studies of normal aging, of
genetic mutations that cause disease, and of environmental factors that affect
disease risk are revealing cellular and molecular alterations that may cause
excessive oxidative stress and trigger neuronal apoptosis. Accumulation of self
aggregating proteins such as amyloid beta-peptide, tau, alpha-synuclein, and
huntingtin may be involved in apoptosis both upstream and downstream of oxidative
stress. Membrane-associated oxidative stress resulting in perturbed lipid
metabolism and disruption of cellular calcium homeostasis may trigger apoptosis
in several different neurodegenerative disorders. Counteracting neurodegenerative
processes are an array of mechanisms including neurotrophic factor signaling,
antioxidant enzymes, protein chaperones, antiapoptotic proteins, and ionostatic
systems. Emerging findings suggest that the resistance of neurons to death during
aging can be enhanced by modifications of diet and lifestyle.
PMID- 17034346
TI - Proteasomal dysfunction: a common feature of neurodegenerative diseases?
Implications for the environmental origins of neurodegeneration.
AB - The neurodegenerative diseases that afflict humans affect different part of the
nervous system and have different symptoms and prognoses, yet they have certain
things in common. One of them is defects in the clearance of abnormal or other
"unwanted" proteins, particularly affecting the proteasome system. In this
review, I advance two concepts: (a) that defects in protein clearance can be a
fundamental cause of neurodegeneration, and (b) that because proteasome
inhibitors are widespread in nature, their ingestion may contribute to
"spontaneous" neurodegeneration.
PMID- 17034347
TI - Protein oxidation and lipid peroxidation in brain of subjects with Alzheimer's
disease: insights into mechanism of neurodegeneration from redox proteomics.
AB - Alzheimer's disease (AD), the leading cause of dementia, involves regionalized
neuronal death, synaptic loss, and an accumulation of intraneuronal,
neurofibrillary tangles and extracellular senile plaques. Although the initiating
causes leading to AD are unknown, a number of previous studies reported the role
of oxidative stress in AD brain. Postmortem analysis of AD brain showed elevated
markers of oxidative stress including protein nitrotyrosine, carbonyls in
proteins, lipid oxidation products, and oxidized DNA bases. In this review, we
focus our attention on the role of protein oxidation and lipid peroxidation in
the pathogenesis of AD. Particular attention is given to the current knowledge
about the redox proteomics identification of oxidatively modified proteins in AD
brain.
PMID- 17034348
TI - DNA oxidation in Alzheimer's disease.
AB - Oxidative damage to DNA may play an important role in aging and neurodegenerative
diseases such as Alzheimer's disease (AD). Attack on DNA by reactive oxygen
species, particularly hydroxyl radicals, can lead to strand breaks, DNA-DNA and
DNA-protein cross-linking, sister chromatid exchange and translocation, and
formation of at least 20 oxidized base adducts. Modification of DNA bases can
lead to mutation and altered protein synthesis. In late-stage AD brain, several
studies have shown an elevation of the base adducts 8 hydroxyguanine (8-OHG), 8
hydroxyadenine (8-OHA), 5-hydroxycytosine (5-OHC), and 5-hydroxyuracil, a
chemical degradation product of cytosine. Several studies have shown a decline in
repair of 8-OHG in AD. Most recently, our studies have shown elevated 8-OHG, 8
OHA, and 5,6-diamino-5-formamidopyrimidine in nuclear and mitochondrial DNA in
mild cognitive impairment, the earliest detectable form of AD, suggesting that
oxidative damage to DNA is an early event in AD and not a secondary phenomenon.
PMID- 17034349
TI - Reproductive hormones modulate oxidative stress in Alzheimer's disease.
AB - Alzheimer's disease (AD) is a neurodegenerative disease characterized by gradual
cognitive decline, impairments in speech and language, and dysfunction in the
sensorimotor systems, culminating in complete reliance on nursing care. Oxidative
stress, caused by an imbalance in the pro-oxidant/antioxidant mechanisms in the
body, has been implicated in AD pathogenesis, as in many other age-associated
diseases such as atherosclerosis, Parkinson disease, and amyotrophic lateral
sclerosis. Although the hormones estrogen, progesterone, testosterone, and
luteinizing hormone are best known for their roles in reproduction, many studies
show these hormones have other roles, including neuroprotection. Changes in the
levels of these hormones that occur in reproductive senescence are hypothesized
to increase risk of AD, as a result of reduced protection against oxidative
insults. The Abeta peptide, overproduction of which is thought to be a key
pathogenic event in the development of AD, is neurotoxic, most likely due to its
ability to promote oxidative stress. The reproductive hormones are known to
influence Abeta metabolism, and this review discusses the beneficial and
detrimental effects these hormones have on Abeta production and oxidative stress,
and their relevance in potential AD therapies.
PMID- 17034350
TI - Oxidative damage in Huntington's disease pathogenesis.
AB - Huntington's disease (HD) is a devastating neurodegenerative disorder
characterized by the progressive development of involuntary choreiform movements,
cognitive impairment, neuropsychiatric symptoms, and premature death. These
phenotypes reflect neuronal dysfunction and ultimately death in selected brain
regions, the striatum and cerebral cortex being principal targets. The genetic
mutation responsible for the HD phenotype is known, and its protein product,
mutant huntingtin (mhtt), identified. HD is one of several "triplet repeat"
diseases, in which abnormal expansions in trinucleotide repeat domains lead to
elongated polyglutamine stretches in the affected gene's protein product. Mutant
htt-mediated toxicity in the brain disrupts a number of vital cellular processes
in the course of disease progression, including energy metabolism, gene
transcription, clathrin-dependent endocytosis, intraneuronal trafficking, and
postsynaptic signaling, but the crucial initiation mechanism induced by mhtt is
still unclear. A large body of evidence, however, supports an early and critical
involvement of defects in mitochondrial function and CNS energy metabolism in the
disease trigger. Thus, downstream death-effector mechanisms, including
excitotoxicity, apoptosis, and oxidative damage, have been implicated in the
mechanism of selective neuronal damage in HD. Here we review the current evidence
supporting a role for oxidative damage in the etiology of neuronal damage and
degeneration in HD.
PMID- 17034351
TI - On the relation of oxidative stress to neuroinflammation: lessons learned from
the G93A-SOD1 mouse model of amyotrophic lateral sclerosis.
AB - The central nervous system (CNS) presents both challenges and opportunities to
researchers of redox biochemistry. The CNS is sensitive to oxidative damage
during aging or disease; excellent transgenic models of specific
neurodegenerative diseases have been created that reproduce oxidative stress
components of the corresponding human disorder. Mouse models of familial
amyotrophic lateral sclerosis (ALS) based on overexpressed mutant human Cu, Zn
superoxide dismutase (SOD1) are cases in point. These animals experience
predictably staged, age-dependent motor neuron degeneration with profound
cellular and biochemical damage to nerve fibers and spinal cord tissue. Severe
protein and lipid oxidation occurs in these animals, apparently as an indirect
consequence of protein aggregation or cytopathic protein-protein interactions, as
opposed to aberrant redox catalysis by the mutant enzyme. Recent studies of G93A
SOD1 mice and rats suggest that oxidative damage is part of an unmitigated
neuroinflammatory reaction, possibly arising in combination from mitochondrial
dysfunction plus pathophysiologic activation of both astrocytes and microglia.
Lesions to redox signal-transduction pathways in mutant SOD1+ glial cells may
stimulate broad-spectrum upregulation of proinflammatory genes, including
arachidonic acid-metabolizing enzymes [e.g., cyclooxygenase-II (COX-II) and 5
lipoxygenase (5LOX)]; nitric oxide synthase (NOS) isoforms; cytokines
(particularly tumor necrosis factor alpha, TNF-alpha); chemokines; and
immunoglobulin Fc receptors (FcgammaRs). The integration of these processes
creates a paracrine milieu inconsistent with healthy neural function. This review
summarizes what has been learned to date from studies of mutant SOD1 transgenic
animals and demonstrates that the G93A-SOD1 mouse in particular is a robust
laboratory for the study of neuroinflammation and redox biochemistry.
PMID- 17034352
TI - Oxidative stress and therapeutic approaches in HIV dementia.
AB - Despite the rapidly increasing incidence of HIV infection worldwide and the
increasing prevalence of HIVassociated cognitive impairment, even in patients
adequately treated with antiretroviral therapy, currently no effective treatment
exists for HIV dementia. A broad range of studies using either brain or
cerebrospinal fluid (CSF) tissues from well-characterized patients with HIV
dementia, animal models, and in vitro studies from several laboratories using HIV
infected cells or HIV proteins provide overwhelming evidence for oxidative stress
in mediating neuronal injury in this patient population. These studies also
suggest that patients with apolipoprotein E (ApoE) 4 allele are more susceptible
to such oxidative damage. In this review, we provide a critical analysis of these
studies, including the few clinical trials that have used antioxidants to treat
HIV dementia. We also discuss several novel agents with potent antioxidative
properties and provide a rationale for combination antioxidant and
neuroprotective therapy.
PMID- 17034353
TI - Ischemic preconditioning triggers nuclear translocation of thioredoxin and its
interaction with Ref-1 potentiating a survival signal through the PI-3-kinase-Akt
pathway.
AB - Thioredoxin (Trx-1), a key mediator of cellular redox homeostasis and cell
survival, is implicated in redox signaling in the ischemic myocardium. To
investigate further its mechanism of action, Trx expression in rat heart was
suppressed by direct injection of small hairpin RNA against Trx-1 (shRNA-Trx-1).
Forty-eight hours after treatment, hearts were excised for isolated working-heart
preparation. A group of hearts was preconditioned (PC) by subjecting them to four
cyclic episodes of 5-min ischemia, each followed by 10 min of reperfusion. All
the hearts, PC or non-PC, were subjected to 30-min ischemia followed by 2 h of
reperfusion. As expected, the PC hearts exhibited improved ventricular function,
reduced infarct size, and cardiomyocyte apoptosis. Also in PC hearts, an increase
was noted in Trx-1 and other cardioprotective and redox-regulated proteins like
Ref-1, phospho-Akt, and NF-kappaB DNA-binding activity. PC also caused nuclear
translocation of Trx-1 and Ref-1 followed by their association. However, in
hearts treated with shRNA-Trx 1, the cardioprotective effects of PC were
abolished along with a concomitant decrease in nuclear localized Trx-1 and Ref-1,
along with a decrease in phospho-Akt and NF-kappaB. These results demonstrate
that PC triggers translocation of Trx-1 into the nucleus, where it becomes
associated with Ref-1 and performs redox signaling through the activation of NF
kappaB and an increase in prosurvival signal inducer phospho-Akt.
PMID- 17034354
TI - Oxidative stress and growth-regulating intracellular signaling pathways in
cardiac myocytes.
AB - The toxic effects of oxidative stress on cells (including cardiac myocytes, the
contractile cells of the heart) are well known. However, an increasing body of
evidence has suggested that increased production of reactive oxygen species (ROS)
promotes cardiac myocyte growth. Thus, ROS may be 'second messenger' molecules in
their own right, and growth-promoting neurohumoral agonists might exert their
effects by stimulating production of ROS. The authors review the principal growth
promoting intracellular signaling pathways that are activated by ROS in cardiac
myocytes, namely the mitogen-activated protein kinase cascades (extracellular
signal-regulated kinases 1/2, c-Jun N-terminal kinases, and p38-mitogen-activated
protein kinases) and the phosphoinositide 3-kinase/protein kinase B (Akt)
pathway. Possible mechanisms are discussed by which these pathways are activated
by ROS, including the oxidation of active site cysteinyl residues of protein and
lipid phosphatases with their consequent inactivation, the potential involvement
of protein kinase C or the apoptosis signal-regulating kinase 1, and the current
models for the activation of the guanine nucleotide binding protein Ras.
PMID- 17034355
TI - The telomere-telomerase axis and the heart.
AB - The preservation of myocyte number and cardiac mass throughout life is dependent
on the balance between cell death and cell division. Rapidly emerging evidence
indicates that new myocytes can be formed through the activation and
differentiation of resident cardiac progenitor cells. The critical issue is the
identification of mechanisms that define the aging of cardiac progenitor cells
and, ultimately, their inability to replace dying myocytes. The most reliable
marker of cellular senescence is the modification of the telomere-telomerase
axis, together with the expression of the cell cycle inhibitors p16INK4a and p53.
Cellular senescence is characterized by biochemical events that occur within the
cell. In this regard, one of the most relevant processes is represented by
repeated oxidative stress that may evolve into the activation of the cell death
program or result in the development of a senescent phenotype. Thus, the
modulation of telomerase activity and the control of telomeric length, together
with the attenuation of the formation of reactive oxygen species, may represent
important therapeutic tools in regenerative medicine and in prevention of aging
and diabetic cardiomyopathies.
PMID- 17034356
TI - Role of thioredoxin in cell growth through interactions with signaling molecules.
AB - The thioredoxin system helps maintain a reducing environment in cells, but
thioredoxin functions as more than simply an antioxidant. Thioredoxin functions
depend on the protein's redox state, as determined by two conserved cysteines.
Key biologic activities of thioredoxin include antioxidant, growth control, and
antiapoptotic properties, resulting from interaction with target molecules
including transcription factors. Mechanisms by which thioredoxin regulates cell
growth include binding to signaling molecules such as apoptosis signal-regulating
kinase-1 (ASK-1) and thioredoxin-interacting protein (Txnip). The molecular
interplay between thioredoxin, ASK-1, and Txnip potentially influences cell
growth and survival in diverse human diseases such as cancer, diabetes, and heart
disease. In this review, we focus on the structure of thioredoxin and its
functional regulation of cell growth through the interactions with signaling
molecules.
PMID- 17034357
TI - Role of reversible, thioredoxin-sensitive oxidative protein modifications in
cardiac myocytes.
AB - Reactive oxygen species (ROS) are important mediators of myocardial remodeling.
However, the precise molecular mechanisms by which ROS exert their effects are
incompletely understood. ROS induce oxidative posttranslational protein
modifications that can regulate the function of structural, functional, and
signaling proteins. For example, oxidative modification of free reactive thiols
(S-thiolation) on the small G protein Ras increases Ras activity and thereby
promotes ROS-dependent hypertrophic signaling in cardiac myocytes. By reducing
thiols and restoring reversible thiol modifications, thioredoxin and glutaredoxin
can act as regulators of ROS-mediated protein function. Understanding the
regulation and functional relevance of oxidative protein modifications in
myocardial remodeling may lead to new therapeutic strategies.
PMID- 17034358
TI - Reactive oxygen species drives myocardial angiogenesis?
AB - Neovascularization, the natural physiological process of formation of new blood
vessels, is extremely important for ameliorating the function of the heart that
undergoes ischemic stress. This process is potentially important for the
treatment of ischemic heart and limb diseases, which includes formation of
capillaries (angiogenesis) and collateral arteries. Ischemia or coronary artery
occlusion induces vascular endothelial growth factor (VEGF) in the experimental
rat myocardial infarction model, and this molecule encourages development of
coronary collateral circulation and retention of the blood supply to the ischemic
area. Restoration of the blood supply to the ischemic area prevents cardiomyocyte
death and cardiac remodeling. Among the various triggers and enhancers of
angiogenesis, hypoxic or ischemic preconditioning, as well as pharmacologic
agents such as statin and resveratrol, have been identified as important stimuli
for the induction of new vessel growth. It has already been demonstrated that the
VEGF family and its receptor system is the fundamental regulator in the redox
cell signaling of angiogenesis. This review article will focus on the role of
reactive oxygen species in the process of myocardial angiogenesis.
PMID- 17034359
TI - Elevated serum 8-oxo-dG in hemodialysis patients: a marker of systemic
inflammation?
AB - Does inflammation, as assessed by high sensitivity C-reactive protein (hs-CRP),
in patients with end-stage renal disease (ESRD) tightly associate with increased
serum levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8- oxo-dG)? Increased
oxidative stress and inflammation have both been highlighted among several
nontraditional risk factors for cardiovascular disease, which is the main cause
of mortality in ESRD patients. In contrast to oxidative stress effects on
proteins and lipids, DNA base damage has not been well demonstrated in ESRD. Two
groups of hemodialysis patients were studied, one group with persistent
inflammation (n = 13, with constant elevation of CRP > 10 mg/L for 6 months) and
one group of noninflamed patients (n = 19, with constant CRP < 10 mg/L for 6
months). Serum 8-oxo-dG was significantly elevated in persistent inflammation in
comparison to noninflamed patients. At an individual level, a significant
correlation was found between serum 8-oxo-dG and hsCRP. Extracellular 8-oxo-dG
leads to intracellular oxidative damage on the nucleotide pool, thus providing a
sensitive marker for inflammatory response. Serum levels of 8-oxo-dG, in
combination with other inflammatory markers, serve as useful diagnostic tools for
identification of patients in risk for inflammatory complications.
PMID- 17034360
TI - 6th COSTAM/SFRR (ASEAN/Malaysia) International Workshop on Micronutrients,
Oxidative Stress, and the Environment.
AB - The 6(th) COSTAM/SFRR (ASEAN/Malaysia) workshop, "Micronutrients, Oxidative
Stress, and the Environment," was held from June 29 to July 2 at Holiday Inn
Damai Beach Resort in Kuching, Sarawak. Two hundred twenty participants from 17
countries presented recent advances on natural antioxidants in the area of
oxidative stress and molecular aspects of nutrition. Natural products and
research are an important program in academic institutions and are experiencing
unprecedented interest and growth by the scientific community and public health
authorities. Progress is being driven by better understanding of the molecular
mechanisms of the relation between oxidative stress and micronutrient action. The
gathering of scientists from around the world was fruitful, and we hope that
future work will be developed by the formal and informal interactions that took
place in this beautiful tropical setting.
PMID- 17034361
TI - Adiponectin inhibits superoxide generation by human neutrophils.
AB - Adiponectin (Ad), a member of the adipocytokine family, has been reported to
possess antiinflammatory properties. We investigated the effects of full-length
human Ad (hAd) on phorbol 12-myristate 13-acetate (PMA)-induced O2-* generation
by human neutrophils. hAd, even at the lowest tested concentration of 0.001
microg/ml, after 30-min pretreatment of cells, significantly inhibited O2-*
generation by neutrophils stimulated with PMA (100 nM). However, no relation
between the dose of hAd and extent of inhibition of PMA-induced O2-* generation
was observed with increasing the concentration of hAd up to 1 microg/ml. hAd also
significantly inhibited neutrophil O2-* generation stimulated by N-formyl
methionyl-leucyl-phenylalanine (100 microM) and diacylglycerol (500 nM), as well
as the PMA-induced neutrophil nitroblue tetrazolium reduction and H2O2 formation.
Pretreatment of neutrophils with pronase-digested hAd failed to inhibit the PMA
induced O2-* generation. For the first time, this study revealed that Ad
inhibited O2-* generation by neutrophils, possibly through regulation of NADPH
oxidase.
PMID- 17034362
TI - Redox control of apoptosis: an update.
AB - The redox environment of the cell is currently thought to be extremely important
to control cell growth, differentiation, and apoptosis as many redox-sensitive
proteins characterize these networks. A recent, widely accepted theory is that
free radicals are not only dangerous species but, at low concentration, they have
been designed by evolution to participate in the maintenance of cellular redox
(reduction/oxidation) homeostasis. This notion derives from the evidence that
cells constantly generate free radicals both as waste products of aerobic
metabolism and in response to a large variety of stimuli. Free radicals, once
produced, provoked cellular responses (redox regulation) against oxidative stress
transducing the signals to maintain the cellular redox balance. Growing evidence
suggests that in many instances the production of radical species is tightly
regulated and their downstream targets are very specific, indicating that
reactive oxygen species and reactive nitrogen species actively participate in
several cell-signalling pathways as physiological "second messengers." In this
review, we provide a general overview and novel insights into the redox-dependent
pathways involved in programmed cell death.
PMID- 17034364
TI - The lipidation status of acute-phase protein serum amyloid A determines
cholesterol mobilization via scavenger receptor class B, type I.
AB - During the acute-phase reaction, SAA (serum amyloid A) replaces apoA-I
(apolipoprotein A-I) as the major HDL (high-density lipoprotein)-associated
apolipoprotein. A remarkable portion of SAA exists in a lipid-free/lipid-poor
form and promotes ABCA1 (ATP-binding cassette transporter A1)-dependent cellular
cholesterol efflux. In contrast with lipid-free apoA-I and apoE, lipid-free SAA
was recently reported to mobilize SR-BI (scavenger receptor class B, type I)
dependent cellular cholesterol efflux [Van der Westhuyzen, Cai, de Beer and de
Beer (2005) J. Biol. Chem. 280, 35890-35895]. This unique property could strongly
affect cellular cholesterol mobilization during inflammation. However, in the
present study, we show that overexpression of SR-BI in HEK-293 cells (human
embryonic kidney cells) (devoid of ABCA1) failed to mobilize cholesterol to lipid
free or lipid-poor SAA. Only reconstituted vesicles containing phospholipids and
SAA promoted SR-BI-mediated cholesterol efflux. Cholesterol efflux from HEK-293
and HEK-293[SR-BI] cells to lipid-free and lipid-poor SAA was minimal, while
efficient efflux was observed from fibroblasts and CHO cells (Chinese-hamster
ovary cells) both expressing functional ABCA1. Overexpression of SR-BI in CHO
cells strongly attenuated cholesterol efflux to lipid-free SAA even in the
presence of an SR-BI-blocking IgG. This implies that SR-BI attenuates ABCA1
mediated cholesterol efflux in a way that is not dependent on SR-BI-mediated re
uptake of cholesterol. The present in vitro experiments demonstrate that the
lipidation status of SAA is a critical factor governing cholesterol acceptor
properties of this amphipathic apolipoprotein. In addition, we demonstrate that
SAA mediates cellular cholesterol efflux via the ABCA1 and/or SR-BI pathway in a
similar way to apoA-I.
PMID- 17034366
TI - Developmental windows and environment as important factors in the expression of
genetic information: a cardiovascular physiologist's view.
AB - Genetic studies in humans and rodent models should help to identify altered genes
important in the development of cardiovascular diseases, such as hypertension.
Despite the considerable research effort, it is still difficult to identify all
of the genes involved in altered blood pressure regulation thereby leading to
essential hypertension. We should keep in mind that genetic hypertension and
other cardiovascular diseases might develop as a consequence of early errors in
well-co-ordinated systems regulating cardiovascular homoeostasis. If these early
abnormalities in the ontogenetic cascade of expression of genetic information
occur in critical periods of development (developmental windows), they can
adversely modify subsequent development of the cardiovascular system. The
consideration that hypertension and/or other cardiovascular diseases are late
consequences of abnormal ontogeny of the cardiovascular system could explain why
so many complex interactions among genes and environmental factors play such a
significant role in the pathogenesis of these diseases. The detailed description
and precise time resolution of major developmental events occurring during
particular stages of ontogeny in healthy individuals (including advanced
knowledge of gene expression) could facilitate the detection of abnormalities
crucial for the development of cardiovascular alterations characteristic of the
respective diseases. Transient gene switch-on or switch-off in specific
developmental windows might be a useful approach for in vivo modelling of
pathological processes. This should help to elucidate the mechanisms underlying
cardiovascular diseases (including hypertension) and to develop strategies to
prevent the development of such diseases.
PMID- 17034367
TI - A phase I radioimmunolocalization trial of humanized monoclonal antibody huA33 in
patients with gastric carcinoma.
AB - In order to determine the in vivo characteristics of huA33, an open label dose
escalation biopsy-based phase I clinical trial and radioimmunolocalization study
were conducted with a complement determinant region-grafted humanized monoclonal
antibody against the A33 antigen in patients with gastric carcinoma. Thirteen
patients were entered onto one of four dose levels (1.0, 2.0, 5.0 or 10.0
mg/m(2)). Patients with locally advanced (UICC-TNM [International Union Against
Cancer-tumor, node, metastasis] stage over 2 but resectable at clinical
diagnosis) gastric carcinoma received a single infusion of (131)I-huA33 1 week
prior to surgery. Adverse events were monitored, and imaging studies with gamma
camera plus ex vivo scintigraphy of the resected specimen, biodistribution study
by dosimetry analysis of the biopsied and resected tissues, and
immunohistochemical analysis were carried out and evaluated. No dose-limiting
toxicity was observed during the trial. Therefore, the maximum tolerated dose was
not reached. Although cancer tissues with + intensity and <25% extent by
immunostaining in biopsied frozen sections did not show positive imaging or
postoperative dosimetry findings, cancers with ++ or +++ intensity or wide (>25%)
extent by frozen and paraffin sections in the biopsied specimen showed positive
ex vivo tumor images and positive antigen expression in resected gastric cancer
specimens, and the biodistribution analysis showed tumor uptake of (131)I-huA33.
In conclusion, humanized monoclonal antibody huA33 demonstrated selective
localization to gastric cancer that expressed A33 antigen strongly. These
excellent targeting characteristics of huA33 indicate potential for targeted
therapy of advanced gastric cancer that is refractory to cytotoxic therapy, and
could also be exploitable for curatively resected early gastric cancer in an
adjuvant setting.
PMID- 17034365
TI - Ubiquitin-binding domains.
AB - The covalent modification of proteins by ubiquitination is a major regulatory
mechanism of protein degradation and quality control, endocytosis, vesicular
trafficking, cell-cycle control, stress response, DNA repair, growth-factor
signalling, transcription, gene silencing and other areas of biology. A class of
specific ubiquitin-binding domains mediates most of the effects of protein
ubiquitination. The known membership of this group has expanded rapidly and now
includes at least sixteen domains: UBA, UIM, MIU, DUIM, CUE, GAT, NZF, A20 ZnF,
UBP ZnF, UBZ, Ubc, UEV, UBM, GLUE, Jab1/MPN and PFU. The structures of many of
the complexes with mono-ubiquitin have been determined, revealing interactions
with multiple surfaces on ubiquitin. Inroads into understanding polyubiquitin
specificity have been made for two UBA domains, whose structures have been
characterized in complex with Lys48-linked di-ubiquitin. Several ubiquitin
binding domains, including the UIM, CUE and A20 ZnF (zinc finger) domains,
promote auto-ubiquitination, which regulates the activity of proteins that
contain them. At least one of these domains, the A20 ZnF, acts as a ubiquitin
ligase by recruiting a ubiquitin-ubiquitin-conjugating enzyme thiolester adduct
in a process that depends on the ubiquitin-binding activity of the A20 ZnF. The
affinities of the mono-ubiquitin-binding interactions of these domains span a
wide range, but are most commonly weak, with Kd>100 microM. The weak interactions
between individual domains and mono-ubiquitin are leveraged into physiologically
relevant high-affinity interactions via several mechanisms: ubiquitin
polymerization, modification multiplicity, oligomerization of ubiquitinated
proteins and binding domain proteins, tandem-binding domains, binding domains
with multiple ubiquitin-binding sites and co-operativity between ubiquitin
binding and binding through other domains to phospholipids and small G-proteins.
PMID- 17034368
TI - A new, simple method for quantifying gemcitabine triphosphate in cancer cells
using isocratic high-performance liquid chromatography.
AB - A deoxycytidine analog, gemcitabine (dFdC), is effective for treating solid
tumors and hematological malignancies. After being transported into cancer cells,
dFdC is phosphorylated to dFdC triphosphate (dFdCTP), which is subsequently
incorporated into the DNA strand, thereby inhibiting DNA synthesis. Intracellular
dFdCTP is the critical determinant for dFdC cytotoxicity, so therapeutic drug
monitoring or in vitro testing of the capability of cancer cells to accumulate
dFdCTP may be informative for optimizing dFdC administration. We have developed a
new isocratic-elution high-performance liquid chromatography method for
quantifying dFdCTP in cancer cells. Samples (500 microL) were eluted
isocratically using 0.06 M Na(2)HPO(4) (pH 6.9) containing 20% acetonitrile, at a
constant flow rate of 0.7 mL/min and at ambient temperature. Separation was
carried out using an anion-exchange column (TSK gel DEAE-2SW; 250 mm x 4.6 mm
inside diameter, particle size 5 microL) and monitored at 254 nm. The standard
curve was linear with low within-day and interday variability. The lower
detection limit (20 pmol) was as sensitive as that of the previous gradient
elution method. dFdCTP was well separated from other nucleoside triphosphates.
The method could measure dFdCTP in cultured or primary leukemic cells treated in
vitro with dFdC. The method was also applicable to simultaneous determination of
dFdCTP and cytarabine triphosphate, the results of which demonstrated ara-CTP
production augmented by dFdC pretreatment. Thus, our isocratic high-performance
liquid chromatography assay method will be of great use because of its
sensitivity and simplicity as well as its applicability to biological materials.
PMID- 17034370
TI - Retinoids and wound healing.
AB - BACKGROUND: Retinoids are widely used in dermatology and may play a role in wound
healing. The exact role of retinoids in wounds is confusing and controversial,
however. Systemic retinoids are presumed to be detrimental to wound healing;
however, this standard is based on isolated reports. OBJECTIVE: The objective was
to provide a critical review of the available literature regarding the role of
both topical and systemic retinoids in various aspects of wound healing.
CONCLUSIONS: Pretreatment with retinoids likely promotes wound healing after
facial resurfacing procedures and full- or partial-thickness wounds. While the
evidence is mixed regarding the effects of retinoids applied to fresh and healing
wounds, the majority of the evidence available shows favorable wound-healing
properties in this setting. The medical-legal standard regarding the avoidance of
facial resurfacing and surgical procedures in patients on or recently completing
a course of systemic retinoids was likely prematurely established.
PMID- 17034371
TI - Histometric and histochemical analysis of the effect of trichloroacetic acid
concentration in the chemical reconstruction of skin scars method.
AB - BACKGROUND: Atrophic scars can be induced by various causes, including severely
inflamed acne, chicken pox, and trauma. Many treatment modalities are used for
reconstructing and improving the appearance of scars with various treatment
results. OBJECTIVE: A recent report shows the clinical efficacy of the chemical
reconstruction of skin scars (CROSS) method, which consists of the focal
application of trichloroacetic acid (TCA) in a higher concentration. Histometric
analysis of the CROSS method, however, has not yet been established. METHODS: In
this study, five hairless mice were used to evaluate the effect of the CROSS
method and to analyze the difference between the CROSS method and simple TCA
application. RESULTS: Similar histologic changes were observed in the two
methods, including epidermal and dermal rejuvenation with new collagen
deposition. These changes, however, were more prominent in the CROSS method
treated areas, particularly when 100% TCA was used. CONCLUSION: The results of
this study suggest that treatment of atrophic scars using the CROSS method is
more effective than simple application of TCA in activating fibroblasts in the
dermis and increasing the amount of collagen.
PMID- 17034373
TI - Periorbital syringoma: a pilot study of the efficacy of low-voltage
electrocoagulation.
AB - BACKGROUND: Management of periorbital syringomas is problematic and avoided by
many inexperienced physicians. The medical literature presently prefers CO(2)
laser resurfacing to many other modalities, but the subject of electrosurgery has
not been well explored. OBJECTIVES: To evaluate the clinical efficacy of
electrocoagulation at low voltages in treating periorbital syringomas. MATERIALS
AND METHODS: Twenty cases were collected during the period of 2002 through 2005.
All cases were photographed before treatment with a dual-frequency 4-MHz
radiofrequency device (Surgitron, Ellman International, Inc., Hewlett, NY) at a
power of 1 to 2 in electrocoagulation mode. Six-week follow-up visits were
scheduled to discuss occurrences and expectations, observe treatment effects, and
apply further electrosurgery if needed. RESULTS: Clinical improvement increased
with each subsequent treatment session. All patients scored either moderate or
marked clinical improvement by their final visits, with 60% (11/18) revealing a
marked clinical improvement (i.e., >70% clearance). The most common encountered
adverse effects consisted of periorbital burning, swelling, redness, and
pigmentary changes. CONCLUSION: Low-voltage electrocoagulation is an effective
therapy for periorbital syringoma and should be considered when treating this
difficult condition. To our knowledge, this is the first study utilizing
electrocoagulation for removal of syringomas.
PMID- 17034372
TI - Eflornithine cream combined with laser therapy in the management of unwanted
facial hair growth in women: a randomized trial.
AB - BACKGROUND: Eflornithine cream is approved for the reduction of unwanted facial
hair in women. The mechanism of action for eflornithine is reduction in
follicular cell growth rate, while laser photoepilation heats hair and adjacent
tissues to suspend growth. OBJECTIVE: The objective was to assess the efficacy
and safety of eflornithine or vehicle with laser therapy in the treatment of
unwanted facial hair in women. METHODS: Subjects were randomized to treatment
with eflornithine on one side of the face and vehicle on the contralateral side
for 34 weeks. Subjects received Nd:YAG or alexandrite laser therapy to both sides
of the face at Weeks 2 and 10. Blinded evaluations included left to right
comparisons and appearance relative to baseline. RESULTS: Fifty-four women
completed the trial. From Weeks 6 through 22, eflornithine-treated sides showed
significant reduction in hair growth. By Week 34, no significant differences were
seen. Subject grading showed significant and persistent hair reduction through
Week 34 for eflornithine-treated sides. The safety profile for combination
therapy is similar to eflornithine alone. CONCLUSION: Eflornithine is safely used
in conjunction with laser hair removal treatments and promotes more rapid hair
removal when combined with laser treatment. Patients demonstrate a clear
preference for treatment with laser and eflornithine.
PMID- 17034374
TI - Treatment of osmidrosis with the Cavitron ultrasonic surgical aspirator.
AB - BACKGROUND: Axillary osmidrosis is an uncomfortable condition that can be a
personal or social handicap. OBJECTIVE: The objective was to present the
treatment of osmidrosis with the Cavitron ultrasonic surgical aspirator (CUSA).
MATERIALS AND METHODS: Fifteen patients (3 males and 12 females) underwent
surgery for bilateral axillary osmidrosis with the CUSA. RESULTS: The outcome of
this operation with the CUSA was evaluated by the patients themselves according
to the following criteria. Postoperative improvement was evaluated as good when
the odor was decreased by >75%, fair when it was decreased by > or =50 and < or
=75%, and poor when it was decreased by <50%. A total of 15 patients (3 males and
12 females) were evaluated. Eight patients (53.3%) had a good result, 6 patients
(40%) had a fairly good result, and 1 patient (6.7%) had a poor result. None of
the patients experienced any complications, such as skin necrosis, infection, or
serous cyst. One dissatisfied patient underwent reoperation and achieved a good
result after the second procedure. CONCLUSIONS: This treatment of osmidrosis with
the CUSA achieves satisfactory therapeutic efficacy.
PMID- 17034375
TI - Reproducibility of two four-point clinical severity scores for lateral canthal
lines (crow's feet).
AB - BACKGROUND: Several clinical scoring systems have been used to evaluate the
efficacy of botulinum toxin A in the treatment of hyperkinetic wrinkles. So far
very few have been investigated for their reproducibility. OBJECTIVE: The aim of
this study was to investigate the reproducibility of two clinical four-point
scales for lateral canthal lines (crow's feet), at rest and at maximum smile.
MATERIAL AND METHODS: Based on standardized photographs, a consensus atlas
depicting the different severity grades [from 0 (none) to 3 (severe)] was
developed. After training based on the atlas, 49 photographs at rest and 48 at
maximum smile were graded by the same group of investigators on 2 consecutive
days (n=9 on Day 1; n=8 on Day 2). The scores were compared for reproducibility
using kappa statistics. RESULTS: Overall, reproducibility was good for both
scales. Interobserver reproducibility showed an agreement of 0.6 at rest and 0.58
at maximum smile (unweighted kappa). Intraobserver reproducibility showed an
agreement between 0.47 and 0.86 at rest and between 0.62 and 0.81 at maximum
smile (unweighted kappa). Using weighted kappa analysis, the agreement ranged
between 0.63 and 0.91 at rest and between 0.71 and 0.85 at maximum smile.
CONCLUSION: The clinical scales using scores of 0 to 3 for crow's feet, both at
rest and at maximum smile, show a good inter- and intraobserver reproducibility.
The use of these scores in clinical trials can be recommended.
PMID- 17034376
TI - Actinic keratoses and the incidence of occult squamous cell carcinoma: a clinical
histopathologic correlation.
AB - BACKGROUND: The ability to clinically diagnose actinic keratoses (AKs) lesions
has been taken for granted for some time. The importance of the malignant
potential of these lesions is well known. However, a recent Phase IV, multicenter
study assessing the long-term benefit of aminolevulinic acid-based photodynamic
therapy provided a unique opportunity to prospectively examine the clinical
histopathologic correlation of AKs. OBJECTIVE: The objective was to characterize
the histopathology of clinically diagnosed AK lesions in the study population.
METHODS: Punch biopsies of 220 clinically diagnosed untreated AKs were performed
at baseline plus 51 lesions unresponsive to treatment (total, 271). RESULTS:
Clinical diagnosis and histopathologic findings agreed in 91% (246/271) of the
lesions biopsied. The balance of the biopsied lesions were: (1) benign changes 4%
(11/271) and (2) occult cutaneous malignancy in 5% (14/271) of the cases, 12
squamous cell carcinomas and 2 basal cell carcinomas. CONCLUSIONS: In this study,
about 1 in 25 clinically diagnosed AK lesions identified by board-certified
dermatologist investigator(s) were occult early-stage squamous cell carcinomas on
histologic assessment, a fact surmised by the medical community that until now
had not been well quantified. These findings should be considered when clinicians
decide how to treat and manage AK patients.
PMID- 17034377
TI - Treatment patterns and cost of nonmelanoma skin cancer management.
AB - INTRODUCTION: Nonmelanoma skin cancer (NMSC) is the most common form of cancer in
the United States, more common than all other cancers combined. The factors that
affect the cost of skin cancer management are not well defined. OBJECTIVE: The
objective was to estimate cost of episodes of NMSC care and the factors that
impact those costs. DESIGN: Medicare Current Beneficiary Survey (MCBS) data from
1999 to 2000 were used to assess costs of episodes of NMSC care. MCBS estimates
of the number of episodes occurring in three service settings (physician's
office, outpatient/ambulatory surgical center, or hospital) and demographics were
obtained. RESULTS: There were 497 episodes of care in 372 patients. Half the
episodes were treated by dermatologists, and two-thirds were managed in
physicians' offices. The mean episode cost for management in the office setting
was 500 dollars (SD, +/- 487 dollars), and costs were higher when the episodes
were treated in either the ambulatory surgical center or the hospital settings,
935 dollars (SD, +/- 456 dollars) and 4,345 dollars (SD, +/- 4939 dollars),
respectively. CONCLUSION: With the rising incidence and cost of NMSC to Medicare,
it is increasingly important to preserve the low-cost management of this disease.
Maintaining care of NMSC in the office-based setting is more cost-efficient than
utilizing ambulatory surgical centers or hospital operating rooms.
PMID- 17034378
TI - Use of intraoperative traction sutures in dermatologic surgery as an aid in
visualization and stabilization in the operative field.
PMID- 17034379
TI - Regression of atypical nevus: an anecdotal dermoscopic observation.
AB - BACKGROUND: Clark nevi (atypical melanocytic nevi) can be considered as risk
markers and potential precursors of melanoma. The authors report on the
morphologic changes of an atypical nevus by dermoscopic follow-up examination
over a 7-year period. CASE REPORT: A 43-year-old man had a brown macule on his
back, sized 5 mm, with an irregular shape, clinically and dermoscopically
diagnosed as an equivocal melanocytic lesion. Dermoscopically during the initial
examination, a predominant reticular pattern with peripheral eccentric
hyperpigmentation in the lower portion of the lesion could be seen. After 7
months, the area of peripheral eccentric hyperpigmentation had regressed, and
after 4.5 years the atypical pigment network had almost disappeared. After 7
years of follow-up, a diffuse area of hypopigmentation and a residual light brown
pigmentation were detectable. The histopathologic diagnosis was consistent with
an atypical junctional nevus with regression with features of a Clark nevus.
CONCLUSION: Based on our observation, even a dermoscopically atypical nevus may
undergo regression as documented by long-term dermoscopic follow-up.
PMID- 17034380
TI - Bilateral hatchet flaps.
PMID- 17034381
TI - Aggressive extraocular sebaceous carcinoma in a 52-year-old man.
PMID- 17034382
TI - Ultralate metastasis of cutaneous melanoma.
PMID- 17034383
TI - Sebaceous carcinoma on the scalp.
PMID- 17034385
TI - Who is still using lip implants?
PMID- 17034384
TI - Mohs micrographic surgery, sentinel lymph node mapping, and estrogen receptor
analysis for the treatment of malignant nodular hidradenoma.
PMID- 17034386
TI - The effect of epidermal graft on a suction blistered donor wound.
PMID- 17034387
TI - Protective positioning of the surgeon's fingers.
PMID- 17034389
TI - Psychological assessment of the headache patient.
AB - Most clinicians agree that psychological factors are important considerations in
the evaluation and treatment of headache patients. There has been a lack of
systematic research, however, that has examined the relationship between these
variables. Attention to such factors may become a greater concern as the
frequency of a patient's headaches increases, there is increased disability
secondary to headaches, and/or there is an inadequate response to usually
effective treatment. In addition, there is no consensus as to the proper method
to assess psychopathology in headache patients.
PMID- 17034390
TI - Basic principles and techniques of cognitive-behavioral therapies for comorbid
psychiatric symptoms among headache patients.
AB - Recent research on headache has focused on identifying the prevalence of
psychiatric disorders in headache patients and discerning the impact of
psychiatric comorbidity on treatment of headache. The presence of comorbid
psychiatric disorders, especially anxiety and depression, in headache patients is
now a well-documented phenomenon. Existing but limited empirical data suggest
that psychiatric comorbidity exacerbates headache and negatively impacts
treatment of headache. Problematically, these findings have not yet eventuated in
improved treatments for individuals suffering from both headache and a
psychiatric disorder(s). The present article is an attempt to describe the
application of cognitive-behavioral therapies (CBT) for depressive and anxiety
disorders to headache patients who present with psychiatric comorbidity. We
discuss the origins of the chronic care model in relation to CBT, review basic
cognitive-behavioral principles in treating depression and anxiety, and offer
clinical recommendations for integrating CBT into existing headache treatment
protocols. Directions for future research are outlined, including the need for
treatment outcome studies that examine the effects of treating comorbid
psychiatric disorders on headache (and vice versa) and the feasibility of
developing an integrated CBT protocol that addresses both conditions
simultaneously.
PMID- 17034391
TI - Pharmacological management of mood and anxiety disorders in headache patients.
AB - There is emerging evidence that treatment of comorbid mood and anxiety disorders
can improve headache treatment outcome when implemented within a comprehensive
program. Effective treatment for comorbid mood and anxiety disorders requires
screening headache patients and accurately diagnosing specific psychiatric
disorders when present. Specific dual-action antidepressant, anticonvulsant, and
atypical antipsychotic medications can serve as dual agents that simultaneously
treat both headaches and a mood or anxiety disorder. Serotonin reuptake
inhibitors and most other antidepressant, anxiolytic, and mood-stabilizing
medications are generally ineffective for headache prophylaxis. However, they can
be safely added to a headache regimen for treatment of a comorbid psychiatric
disorder. Treatment of comorbid psychiatric disorders in headache patients
requires patient education about the psychiatric disorder, its treatment,
possible side-effects, and expected benefits. Clinicians need to be sensitive to
possible stigma that some patients fear from a psychiatric diagnosis or its
treatment.
PMID- 17034392
TI - Behavioral facilitation of medical treatment of headache: implications of
noncompliance and strategies for improving adherence.
AB - Clinical recommendations were gleaned from a review of treatment adherence
published in the regular issue of Headache (released in tandem with this
supplement). The recommendations include: (1) Nonadherence is prevalent among
headache patients, undermines treatment efficacy, and should be considered as a
treatment variable; (2) Calling patients to remind them of appointments and
recalling those who miss a scheduled appointment are fundamentally the most cost
effective adherence-enhancing strategies, insofar as failed appointment-keeping
acts as a ceiling on all future treatment and adherence efforts; (3) Simplified
and tailored medication regimens improve adherence (eg, minimized number of
medications and dosings, fixed-dose combinations, cue-dose training, stimulus
control); (4) Screening and management of psychiatric comorbidities, especially
depression and anxiety, is encouraged; (5) The concept of self-efficacy as a
modifiable psychological process often can be employed to predict and improve
adherence.
PMID- 17034393
TI - Modifiable risk factors for migraine progression (or for chronic daily headaches)
-clinical lessons.
AB - Herein we summarize clinical issues gleaned from a full peer-reviewed article on
modifiable risk factors for migraine. Since migraine is progressive in some but
not in most individuals, identifying patients at risk for progression is crucial.
Key interventions include: (1) Decrease headache frequency with behavioral and
pharmacologic interventions; (2) Monitor the body mass index and encourage
maintenance of normal weight; (3) Avoid medication overuse; (4) Avoid caffeine
overuse; (5) Investigate and treat sleep problems and snoring; (6) Screen and
treat depression and other psychiatric comorbidities. These recommendations have
not been demonstrated to improve outcomes in longitudinal studies.
PMID- 17034394
TI - Sleep and headache disorders: clinical recommendations for headache management.
AB - Clinical practice points were drawn from a review of sleep and headache disorders
published in the regular issue of Headache (released in tandem with this
supplement). The recommendations include: (1) Sleep as well as psychiatric
disorders tend to become prevalent in more complex and severe headache patterns
and regulation of sleep and mood may favorably impact headache threshold; (2)
Specific headache patterns, irrespective of headache diagnosis, are suggestive of
a potential sleep disorder (eg, "awakening" or morning headache, chronic daily
headache); (3) Sleep disorders most implicated with headache include obstructive
sleep apnea, primary insomnia, and circadian phase abnormalities, and treatment
of such sleep disorders may improve or resolve headache; (4) Inexpensive
screening tools (eg, sleep history interview, headache/sleep diary, validated
questionnaires, prediction equations) aid identification of patients warranting
polysomnography; and (5) Pharmacologic and behavioral therapies are effective in
the regulation of sleep and are compatible with usual headache care.
PMID- 17034395
TI - Suggestions for a biopsychosocial approach to treating children and adolescents
who present with headache.
AB - An evidence-based, biopsychosocial approach to the care of pediatric patients who
present with the complaint of headache is recommended. This approach informs
diagnosis and management decisions, is critical for maximizing adherence to the
prescribed headache treatment regimen, and incorporates assessment of the impact
of headache on a child/adolescent's quality of life, disability, and emotional
functioning. Very often, successful treatment of headache leads to improvements
in disability and emotional functioning. When this is not the case, or when the
work-up shows that comorbid headache and psychiatric disorders are present for a
patient, a more comprehensive treatment approach that includes the active
collaboration of pediatric specialists in headache care and mental health care is
warranted.
PMID- 17034396
TI - "Are you talking to me?" confronting behavioral disturbances in patients with
headache.
AB - The famous question, "Are you talking to me?," was coined by Robert DeNiro in his
lead role as Travis Bickle in the Martin Scorsese classic, Taxi Driver. The
phrase also characterizes the troubling encounters that many headache-treating
professionals confront as they attempt to discuss serious matters of care and
compliance with some of their headache patients. Although most headache patients
are eager to take professional advice and guidance, there exists a minority of
patients whose behavior undermines a collaborative relationship between doctor
and patient. In these cases, the physician may need to directly confront this
behavior in order to overcome behavioral barriers that interfere with desirable
treatment outcomes. This article offers explicit means and strategies to engage
difficult patients, increase the likelihood of program adherence and improvement,
and develop a more satisfying doctor-patient relationship, based on clinical
experience in a national referral center for difficult-to-manage headache
patients.
PMID- 17034397
TI - Understanding the patient with complex psychiatric comorbidities: a
psychologist's perspective.
PMID- 17034398
TI - Understanding the headache patient with complex comorbidities: a primary care
physician's perspective.
PMID- 17034399
TI - Understanding the headache patient with complex psychiatric comorbidities: a
neurologist's perspective.
PMID- 17034400
TI - Understanding the headache patient with complex psychiatric comorbidities: a
headache specialist's perspective.
PMID- 17034401
TI - Psychiatric comorbidity with chronic headache: evidence-based clinical
implications--introduction to the supplement.
PMID- 17034402
TI - Mood and anxiety disorders in chronic headache.
AB - Although most individuals with recurrent headache disorders in the general
population do not experience severe psychopathology, population-based studies and
clinical investigations find high rates of comorbidity between headache and mood
and anxiety disorders. When present, psychiatric disorders may complicate
headache treatment and portend a poorer treatment response. The negative
prognosis associated with psychiatric comorbidity emphasizes the importance of
the identification of psychopathology among those with headache beginning at an
early age, and suggests that the treatment of psychiatric comorbidity is
warranted to improve the outcome of headache management. In this article we
describe the mood and anxiety disorders most commonly associated with migraine,
tension-type headache, and chronic daily headache. We provide recommendations for
the assessment of comorbid mood and anxiety disorders as well as a brief overview
of treatment options. Last, we discuss the clinical implications of mood and
anxiety disorders on the treatment and outcome of headache.
PMID- 17034403
TI - Medication overuse headache: biobehavioral issues and solutions.
AB - This article reviews current research on medication-overuse headache (MOH), and
provides clinical suggestions for effective treatment programs. Epidemiological
research has identified reliance on analgesics as a predictive factor in headache
chronicity. MOH can be distinguished as simple (Type I) or complex (Type II).
Simple cases involve relatively short-term drug overuse, relatively modest
amounts of overused medications, minimal psychiatric contribution, and no history
of relapse after drug withdrawal. In contrast, complex cases often present with
multiple psychiatric comorbidities and a history of relapse. Although limited,
current research suggests that comorbid psychiatric disorders are more prevalent
in MOH than in control headache conditions, and may precede the onset of MOH.
There appears to be an elevated risk of family history of substance use disorders
in MOH patients, and an increased risk of MOH in patients with diagnosed
personality disorders. Current studies suggest a high rate of relapse at 3 to 4
years after drug withdrawal and pharmacological treatment, with most relapse
occurring during the first year of treatment. Relapse is a greater problem with
analgesics than ergots or triptans. The addition of behavioral treatment to
prophylactic medication may significantly reduce the risk of relapse over a
period of several years. Clinical recommendations include assessment and
modification of psychological factors that may underlie MOH, provision of
detailed educational information, and combining behavioral treatment with the
current standard of drug withdrawal and use of prophylactic pharmacotherapy.
PMID- 17034404
TI - A review of screening tools for psychiatric comorbidity in headache patients.
AB - Psychiatric comorbidity, especially depression and anxiety, has been well
documented in patients with primary headache disorders. The presence of
psychiatric comorbidity in headache patients is associated with decreased quality
of-life, poorer prognosis, chronification of disease, poorer response to
treatment, and increased medical costs. Despite the prevalence and impact,
screening for psychiatric disorders in headache patients is not systematically
performed, either clinically or in research studies, and there are no guidelines
to suggest which patients should be screened or in what manner. We review a
variety of screening methods and instruments, focusing primarily on self-report
measures and those available in the public domain. Informal verbal screening may
be sufficient in a primary care setting, but should include screening for both
anxiety and depression. Explicit screening for anxiety is important, as anxiety
may have a more significant impact on headache than does depression and may occur
in the absence of clinical depression. Formal screening with instruments that can
identify a variety of psychiatric disorders is appropriate for patients with
daily headache syndromes, patients who are refractory to usual care, and patients
referred for specialty evaluation. Limitations of screening instruments include
the influence of transdiagnostic symptoms and the need for confirmatory
diagnostic interview. The following instruments appear most suitable for use in
headache patients: for depression, the Patient Health Questionnaire Depression
Module, the Beck Depression Inventory-II, or the Beck Depression Inventory
Primary Care; for anxiety, the Beck Anxiety Inventory and the Generalized Anxiety
Disorder 7-item Scale; and for multidimensional psychiatric screening, the
Patient Health Questionnaire or Primary Care Evaluation of Mental Disorders.
PMID- 17034405
TI - The role of intrinsic and induced vulnerability in electrically induced cardiac
arrhythmias.
PMID- 17034406
TI - A beat is born: embryonic development of arrhythmogenesis.
PMID- 17034407
TI - Clustering of ventricular arrhythmias: a therapeutic opportunity or strictly a
marker of poor prognosis?
PMID- 17034408
TI - Dual-chamber pacemakers as long-term telemetry devices: ready for prime-time in
diagnosing unsuspected atrial fibrillation?
PMID- 17034409
TI - Sexual function in women with urinary incontinence treated by pelvic floor
transvaginal electrical stimulation.
AB - INTRODUCTION: Women's sexual dysfunctions (WSD) have been commonly associated
with urinary incontinence (UI). Women with UI and who scored low on the Female
Sexual Function Index (FSFI) showed an improvement in urinary leakage and also in
their sexual life following treatment by transvaginal electrical stimulation
(TES). AIMS: To determine the effects of TES in 37 women complaining of UI, of
whom 23 also had WSD, and to compare the FSFI scores of women with UI and 43
women not affected by UI who underwent routine urologic evaluation. METHODS:
Thirty-seven women complaining of UI were evaluated by voiding diary and with
FSFI before and after 3 months of TES. All had a urogynecologic evaluation and
urodynamic study. MAIN OUTCOME MEASURES: In the voiding diary the women reported
the types of liquid they ingested, urinary frequency, and episodes of urgency and
urine leakage. The domain scores of the FSFI, including desire, arousal,
lubrication, orgasm, satisfaction, and pain, were calculated. TES was conducted
for 15-30 minutes, twice a week for 3 months, using biphasic intermittent current
with a frequency of 50 Hz for stress UI (SUI) and 20 Hz for urge UI (UUI), and
the most tolerable intensity of stimulation. RESULTS: After TES, only two of the
10 women with UUI experienced a few leakage incidents; patients with SUI were
completely dry during TES; and only three reported a few episodes of UI during
intense activities. The five patients with mixed UI improved mainly as regards
urgency. The FSFI scores of patients complaining of UI showed significantly lower
desire and sexual satisfaction, and higher sexual pain than controls. After 3
months, the 23 women affected by WSD, of the 37 participants with UI, reported a
remarkable improvement in their sexual life. CONCLUSIONS: TES was found to be a
safe and effective therapy for selected patients affected by mild to moderate UI.
Because women with UI also complain of WSD compared with the general female
population, an investigation of female sexuality is suggested for these patients.
PMID- 17034410
TI - Nonpalpable scarring of the penile septum as a cause of erectile dysfunction: an
atypical form of Peyronie's disease.
AB - INTRODUCTION: Men with nonpalpable isolated septal scars (ISS) identified with
color duplex ultrasonography (CDU) comprise a group of previously unrecognized
patients with wide-ranging sexual concerns. AIM: We aim to identify the clinical
characteristics of patients presenting with this atypical form of Peyronie's
disease characterized by the absence of palpable deformity. MATERIALS AND
METHODS: Of 482 consecutive patients who presented to a tertiary care erectile
dysfunction (ED) clinic and underwent CDU after satisfying inclusion criteria, 27
(5.6%) men with nonpalpable ISS and no dorsal or ventral plaque were identified.
MAIN OUTCOME MEASURES: International Index of Erectile Function (IIEF), CDU, and
clinical characteristics. RESULTS: The median age of the men with nonpalpable ISS
was 49 years. The length of time from onset of symptoms to presentation was 22
months, and the pretreatment IIEF score was 14. The remaining 455 men who
underwent CDU were of similar age (48 years) but had a markedly lower IIEF score
of 9.5 (statistical median). ISS patients presented with decreased penile
rigidity (20), penile shortening (13), chronic pain with erection (13; mean 33
months), and the inability to maintain an erection (7). Fourteen men had failed
phosphodiesterase-5 inhibitor therapy, and four reported unsatisfactory results.
Management options included retrial with oral agents, intracavernous
pharmacotherapy, verapamil injections, and surgery. CONCLUSIONS: The clinician
should be suspicious for nonpalpable ISS in men with sexual concerns who present
with decreased penile rigidity, length loss, and chronic pain with erection. Our
findings support the use of CDU for this patient group, particularly when
previous treatment has failed, because men with ISS had a greater likelihood of
having no palpable deformity or curvature and ongoing penile pain.
PMID- 17034411
TI - Evaluating the impact of overactive bladder on sexual health in women: what is
relevant?
AB - INTRODUCTION: To assess sexual health, relevant, valid, and reliable
questionnaires need to be used. AIM: To assess the relevance and content validity
of three sexual health questionnaires in women with overactive bladder (OAB) and
urinary incontinence. MAIN OUTCOME MEASURES: Sexual Quality of Life Questionnaire
-Female (SQoL-F), Sexual Function Questionnaire (SFQ), and Pelvic Organ Prolapse
Incontinence Sexual Function Questionnaire (PISQ). METHODS: Women with OAB and
urinary incontinence were recruited from five urology clinics in the United
States; those who were interested in participating were mailed questionnaire
packets with instructions. Each questionnaire item was followed by three
questions regarding the understandability, relevance, and impact of bladder
condition when responding to the question. Patients returned the completed
questionnaires by mail; clinical information was obtained from chart review.
RESULTS: A total of 129 patients (74% response) returned the questionnaires. The
mean age was 56 years; 78% were white; 64% were married. In this sample, 64% had
urge incontinence; 32% had mixed incontinence; and 4% had stress incontinence.
Participants experienced bladder symptoms for a mean of 12.2 years with the
following treatments: surgery (43%), bladder training (26%), exercise/biofeedback
(42%), and medications (67%). SQoL-F items were understood by more than 97% of
the respondents, more than 89% for SFQ, and more than 82% for PISQ. There were
two SQoL-F items, one SFQ item, and 11 PISQ items that less than 60% of the
respondents deemed relevant to their bladder condition. Correlations among
questionnaire items and relevance to bladder condition ranged from 0.04 to 0.64
for the SQoL-F, 0.04 to 0.47 for the SFQ, and 0.01 to 0.58 for the PISQ.
CONCLUSION: Women with OAB found the majority of items on all three
questionnaires to be relevant to their bladder condition. Of these
questionnaires, the SQoL-F had the highest understandability, fewest questions
considered irrelevant, and correlated well with OAB symptoms.
PMID- 17034412
TI - Comparison of colonization dynamics and pathology of mice infected with
enteropathogenic Escherichia coli, enterohaemorrhagic E. coli and Citrobacter
rodentium.
AB - Enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC) and
Citrobacter rodentium (CR) colonize the gastrointestinal tract epithelium via
attaching and effacing lesions. While humans are believed to be the only living
reservoir of typical EPEC and EHEC to have border host specificity, CR is a
restricted mouse pathogen. Recently, conflicting conclusions were reported
concerning the utility of a murine model to study mechanisms of EPEC and EHEC
colonization and infection. We therefore aimed to compare colonization dynamics
of EPEC, EHEC and CR, together with a commensal E. coli (Nissle) as a control, in
the murine. We show that all strains are equally shed in stools over the first 48
h post inoculation. However, while the CR population then rapidly expanded the
EPEC, EHEC and Nissle populations quickly declined to a level just above
detection. We conclude that following oral inoculation EPEC and EHEC develop a
commensal, rather than pathogenic, interaction within the mouse host.
PMID- 17034413
TI - Identification and characterization of ENA ATPases HwENA1 and HwENA2 from the
halophilic black yeast Hortaea werneckii.
AB - Two genes, HwENA1 and HwENA2, which encode ENA-like ATPases in the extremely
halotolerant black yeast Hortaea werneckii, were cloned and sequenced. Although
the expression of both genes is responsive to salt, the transcription of the
HwENA1 gene was induced at a higher level when the cells were exposed to salt
stress, and the expression of HwENA2 gene was higher in the adapted cells,
suggesting their different roles in maintaining alkali cation homeostasis.
According to the phylogenetic tree based on the amino acid sequences, they
represent a new group of fungal P-type ATPases. The comparison of both amino acid
sequences with other fungal ENA ATPases, together with salt- and pH-responsive
gene expression, suggests that newly identified ENA genes could be involved in
maintaining low Na(+)/K(+) content in H. werneckii.
PMID- 17034415
TI - Differential effect of auxotrophies on the release of macromolecules by
Salmonella enterica vaccine strains.
AB - Attenuated Salmonella enterica strains have been widely used as live carriers for
vaccines and therapeutic molecules. Appropriate attenuation has been introduced
into such bacteria for safety reasons and the improvement of strain properties.
Here, we compared two strains that were rendered auxotroph for diaminopimelic
acid or thymidine monophosphate precursors by deletion of the genes asd or thyA,
respectively. Upon removal of the complementing compound from bacterial cultures,
both strains quickly lose their property to form colonies. However, while the
Deltaasd bacteria lysed almost immediately under such conditions, DeltathyA
bacteria remained physically intact during the observation period. As a
consequence, the Deltaasd bacteria released their intracellular content such as
proteins or plasmids into the supernatant. In contrast, no intracellular
component, either proteins or plasmids, could be recovered from the supernatants
of DeltathyA bacteria upon depletion of thymidine. Thus, the release of
macromolecules from the bacterial carrier occurs as a consequence of appropriate
lethal attenuation. This might substitute for sophisticated secretion systems.
PMID- 17034414
TI - Phenotypic characteristics, virulence profile and genetic relatedness of O157
Shiga toxin-producing Escherichia coli isolated in Brazil and other Latin
American countries.
AB - Thirty-eight Shiga toxin-producing Escherichia coli (STEC) O157:H7/H(-) strains
isolated from human infections, cattle and foods in Brazil and in some other
Latin American countries were compared with regard to several phenotypic and
genotypic characteristics. The genetic relatedness of the strains was also
determined by pulsed-field gel electrophoresis (PFGE). Similar biochemical
behaviour was identified, regardless of the origin and country of the strains.
Most (89.5%) strains were sensitive to the antimicrobial agents tested, but
resistance to at least one drug was observed among bovine strains. Although a
diversity of stx genotypes was identified, most (77.8%) of the human strains
harboured stx(2) or stx(2)stx(2c(2vha)), whereas stx(2c(2vha)) prevailed (64.2%)
among strains isolated from cattle. stx(1) and stx(1)stx(2c(2vha)) were the
genotypes identified less frequently, and occurred exclusively among strains
isolated from food and cattle, respectively. Despite differences in the stx
genotypes, all strains carried eae-gamma, efa1, ehx, iha, lpf(O157) and toxB
sequences. Many closely related subgroups (more than 80% of similarity) were
identified by PFGE, and the presence of a particular O157:H7 STEC clone more
related to human infections in Brazil, as well as a common origin for some
strains isolated from different sources and countries in Latin America can be
suggested.
PMID- 17034416
TI - Aryloxoalcanoic compounds induce resistance to antibiotic therapy in urinary
tract infection caused by Escherichia coli.
AB - Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and
ethacrynic acid (ET) is administered to enhance diuresis. These compounds are
structurally analogous to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D),
as they have a chlorinated phenoxy moiety. As these agents are mainly excreted by
the renal route, they could potentially coexist with Escherichia coli in the
urinary tract of infected patients. Induction of the in vitro resistance of E.
coli to hydrophilic antibiotics was determined by increasing the values of the
minimum inhibitory concentration (2-40-fold). These results correlated with
drastically inhibited expression of the hydrophilic bacterial channel OmpF. In
vivo assays were performed in ascending urinary tract infection in female BALB/c
mice. Treatment with the hydrophilic antibiotic cephalexin 25 mg kg(-1) day(-1)
by the oral route diminished renal infection. The CFU mean values in the kidneys
were between 75% and 89% lower than those in animals without treatment.
Simultaneous exposure to CL (at a therapeutic dose, 28.6 mg kg(-1) day(-1)) did
not change the effect of the treatment. In contrast, ET at 2.9 mg kg(-1) day(-1)
or 2,4-D at 70 mg kg(-1) day(-1) inhibited the antibiotic therapeutic effect.
Moreover, 2,4-D dramatically increased bacterial infection after 9 days of
exposure.
PMID- 17034417
TI - Whey-derived free fatty acids suppress the germination of Candida albicans in
vitro.
AB - Bovine whey from the cheese-making industry contains several bioactive factors
that promote health and prevent disease. Although many efforts have been made
over the years to show that immunoglobulins, lactoperoxidase, lactoferrin,
lysosyme and small peptides present in whey have antimicrobial activities against
several pathogenic microorganisms, such activities have not been investigated so
far for the lipid fraction of whey. Here, we have used an in vitro assay-based
fractionation procedure to show that free fatty acids derived from whey cream
specifically inhibit the germination of Candida albicans, a morphologic change
associated with pathogenicity. Further fractionation by HPLC demonstrated that
this activity can be mainly attributed to lauric acid, myristoleic acid, linoleic
acid and arachidonic acid.
PMID- 17034418
TI - Effect of treatment with a colloidal oatmeal lotion on the acneform eruption
induced by epidermal growth factor receptor and multiple tyrosine-kinase
inhibitors.
AB - Current treatment modalities for epidermal growth factor (EGFR)-positive cancers
have recently included the use of antibodies and small-molecule tyrosine-kinase
inhibitors (TKI). A significant limiting step in the use of these agents is
dermatological toxicity, frequently in the form of an acneiform eruption. Present
management modalities for this toxicity are largely ineffective. Colloidal
oatmeal lotion demonstrates multiple anti-inflammatory properties with known
effects on arachidonic acid, cytosolic phospholipase A2 and tumour necrosis
factor-alpha pathways, along with an excellent side-effect profile. Treatment
with colloidal oatmeal was applied to 11 patients with a rash induced by
cetuximab, erlotinib, panitumumab and sorafenib. Of the 10 assessable patients, 6
had complete response and 4 partial response, giving a response rate of 100% with
no associated toxicities. Treatment with colloidal oatmeal lotion is efficient in
controlling the rash associated with EGFR and multiple TKI, and allows
continuation of the antineoplastic treatment.
PMID- 17034419
TI - Erythema elevatum diutinum manifesting as a penile ulcer.
PMID- 17034420
TI - Solar urticaria as a manifestation of Churg-Strauss syndrome.
PMID- 17034421
TI - Anomalies in dermal ridge arrangement in Down's syndrome.
PMID- 17034422
TI - Thorium X and skin cancer: still a problem in the 21st century.
PMID- 17034423
TI - Peripheral neuropathy associated with nodular prurigo.
AB - Nodular prurigo is characterized by nodules and papules that are intensely
pruritic. Thalidomide is used to treat patients with recalcitrant disease.
Because thalidomide may cause peripheral neuropathy, it is current practice to
perform nerve conduction studies to exclude subclinical neuropathy before
treatment. The clinical record of eight patients with nodular prurigo, in whom
thalidomide treatment was proposed, were looked at. Five of them showed evidence
of subclinical neuropathy, thereby contraindicating the use of thalidomide. None
of the patients had any symptoms of a peripheral neuropathy and none was taking
any medications with a recognized potential to cause peripheral neuropathy. We
propose that nodular prurigo may be associated with an underlying peripheral
neuropathy in a subset of patients. In patients with nodular prurigo and
demonstrable peripheral neuropathy, there may be a role for treatment with agents
such as amitryptiline and gabapentin, which are normally used for neuropathic
pain.
PMID- 17034424
TI - Toll-like receptor interactions: tolerance of MyD88-dependent cytokines but
enhancement of MyD88-independent interferon-beta production.
AB - Toll-like receptors (TLRs) signal through two main pathways: a myeloid
differentiation factor (MyD)88-dependent pathway that acts via nuclear factor
kappaB (NF-kappaB) to induce proinflammatory cytokines such as tumour necrosis
factor-alpha (TNF-alpha) and a MyD88-independent pathway that acts via type I
interferons to increase the expression of interferon-inducible genes. Repeated
signalling through TLR4 and a number of other TLRs has been reported to result in
a reduction in the subsequent proinflammatory cytokine response, a phenomenon
known as TLR tolerance. In this study we have shown that, whilst NF-kappaB
activation and production of TNF-alpha and interleukin-12 by murine RAW264.7 and
J774.2 cells in response to stimulation by TLR4, -5, -7 or -9, was reduced by
prior stimulation with TLR4, -5, -7 or -9 ligands, the primary stimulation of
TLR3, which does not use the MyD88 pathway, did not reduce the TNF-alpha or
interleukin-12 responses to subsequent TLR stimulation. The response to TLR3
stimulation was not diminished by prior TLR ligand exposure. Furthermore, the
production of interferon-beta (IFN-beta) following stimulation of TLR3 or -4,
which is MyD88-independent, was increased by prior activation of TLR4, -5, -7 or
9. In contrast, TLR9 ligand-induced IFN-beta production, which is MyD88
dependent, was tolerized by prior TLR stimulation. These results are consistent
with differential regulation of MyD88-dependent and MyD88-independent cytokine
production following serial activation of TLRs.
PMID- 17034426
TI - Involvement of IL-10 in exhaustion of myeloid dendritic cells and rescue by CD40
stimulation.
AB - It has recently been shown that immature dendritic cells (DCs) stimulated by a
danger signal undergo transient maturation followed by exhaustion. However, the
exact mechanism for this has not been elucidated. In this study, we show that
interleukin-10 (IL-10) secreted from transiently matured DCs stimulated by danger
signals is responsible for this rapid DC exhaustion. Blocking of the autocrine IL
10 enabled transient mature DCs to maintain the mature phenotype for several
days. However, these DCs remained phenotypically unstable because the addition of
IL-10 altered the transient mature DCs to exhausted DCs. More importantly,
stimulation of DCs by CD40 protected transient mature DCs from IL-10-dependent
exhaustion, with the result that mature DCs remained stable in the presence of IL
10. Furthermore, in vivo administration of stable mature DCs pulsed with
ovalbumin protein induced antigen-specific cytotoxic T lymphocytes (CTLs)
effectively, whereas neither exhausted DCs nor transient mature DCs were able to
prime a strong antigen-specific CTL response. These results indicate that DC-T
cell engagement via CD40-CD154 is required for stable DC maturation leading to
effective CTL induction. Otherwise, DCs stimulated solely by a danger signal are
temporarily activated, but then rapidly lose their immune-activating capacity
under the influence of autocrine IL-10.
PMID- 17034425
TI - Workshop cluster 1+ gammadelta T-cell receptor T cells from calves express high
levels of interferon-gamma in response to stimulation with interleukin-12 and
18.
AB - Gammadelta T-cell receptor(+) T lymphocytes are an important element of the
innate immune system. Early production of interferon (IFN)-gamma by gammadelta T
cells may have a role in linking innate and adaptive immune responses and
contribute to T helper-1 bias. We investigated the role of cytokines in the
activation and induction of IFN-gamma secretion by bovine workshop cluster 1(+)
(WC1(+)) gammadelta T cells. The effects of culture with interleukin (IL)-12, IL
18, IL-15 and IL-2 were investigated; these cytokines are known to influence
murine and human gammadelta T cells. We report that bovine WC1(+)gammadelta T
cells are synergistically stimulated by IL-12 and IL-18 to secrete large
quantities of IFN-gamma. Neonatal calves were shown to have significantly higher
numbers of circulating WC1(+)gammadelta T cells than adult animals. In addition,
the response of peripheral blood WC1(+)gammadelta T cells was significantly
higher in neonatal calves compared with adult animals. However, in adult animals
the response of lymph node WC1(+)gammadelta T cells to IL-12/IL-18 was more
pronounced than that of peripheral blood WC1(+)gammadelta T cells. We hypothesize
that the induction of IFN-gamma secretion from WC1(+)gammadelta T cells by IL-12
and IL-18 is likely to be an important element of the innate response to
pathogens such as Mycobacterium bovis. The high numbers of WC1(+)gammadelta T
cells in neonatal calves, and their inherent ability to respond to inflammatory
cytokines, could be a key factor in the enhanced responses seen in calves to BCG
vaccination.
PMID- 17034428
TI - Avoiding potential misuses of addiction brain science.
PMID- 17034427
TI - Major histocompatibility complex class II (DR) antigen and costimulatory
molecules on in vitro and in vivo activated human polymorphonuclear neutrophils.
AB - We have previously shown that normal human peripheral blood polymorphonuclear
neutrophils (PMNs) contain cytoplasmic 'stores' of three key molecules normally
associated with antigen presentation and T-cell costimulation, i.e. major
histocompatibility complex class II (DR) antigen, CD80 (B7-1) and CD86 (B7-2).
These cytoplasmic molecules were found to translocate to the cell surface within
a few minutes following cross-linking (X-L) of Mac-1: an early neutrophil
activation signal. In this study we have compared X-L of Mac -1 in parallel with
four other well documented in vitro neutrophil activators: phorbol myristate
acetate, N-formyl methionyl leucyl phenylalanine, lipopolysaccharide, and
phagocytosis of immunoglobulin G-Latex particles. In addition, we have used
paired samples of neutrophils obtained from peripheral blood (as a control) and
synovial fluid from patients with rheumatoid arthritis as a source of in vivo
activated cells. With the exception of phagocytosis, all activators resulted in
the rapid (within 30 min) generation of two populations of activated neutrophils
(designated P1 and P2) based on flow-cytometry measurements of size, granularity
and phenotype. Significant up-regulation of DR and costimulatory molecules was
observed, predominantly on P2 cells, with all activators except phagocytosis.
CD80 and CD86 were noted to respond to the various activation signals in a
different pattern suggesting that their intracellular granule location may be
different. Dual-staining confocal laser microscopy studies showed that CD80 is
largely confined to secretory vesicles (SVs) while CD86 appears to have a much
wider distribution being found in SVs and within secondary (specific) and primary
(azurophilic) granules. Increased surface expression of these antigens was also
observed on P2 synovial fluid neutrophils appearing as large heterogeneous
clusters on the cell surface when visualized by confocal laser microscopy.
PMID- 17034429
TI - Digitizing and democratizing historical research.
PMID- 17034430
TI - Contingency management and the addictions.
PMID- 17034431
TI - Hypothalamic-pituitary-adrenal axis and substance use: so many questions--and we
can answer them.
PMID- 17034432
TI - Matching clients' treatment goals with treatment oriented towards abstinence,
moderation or harm reduction.
PMID- 17034433
TI - Sweden--is alcohol becoming an ordinary commodity?
PMID- 17034434
TI - Contingency management for treatment of substance use disorders: a meta-analysis.
AB - AIMS: To examine the effectiveness of contingency management (CM) techniques in
treating substance use disorders (i.e. illicit drugs, alcohol, tobacco). DESIGN:
Meta-analysis was used to determine the average effect size and potential
moderators in 47 comparisons of the effectiveness of CM from studies based on a
treatment-control group design and published between 1970 and 2002. FINDINGS: The
mean effect size (ES) of CM was positive, with a magnitude of d = 0.42 using a
fixed effects model. The magnitude of the ES declined over time, following
treatment. CM was more effective in treating opiate use (d = 0.65) and cocaine
use (d = 0.66), compared with tobacco (d = 0.31) or multiple drugs (d = 0.42).
Larger effect sizes were associated with higher researcher involvement, earlier
studies and shorter treatment duration. CONCLUSIONS: Study findings suggest that
CM is among the more effective approaches to promoting abstinence during the
treatment of substance use disorders. CM improves the ability of clients to
remain abstinent, thereby allowing them to take fuller advantage of other
clinical treatment components.
PMID- 17034435
TI - Topiramate reduces the harm of excessive drinking: implications for public health
and primary care.
AB - AIMS: Having demonstrated previously the efficacy of topiramate--a sulfamate
substituted fructopyranose derivative-as pharmacotherapy for treating alcohol
dependence, promoting abstinence and reducing the harmful psychosocial
consequences of drinking, we investigated whether topiramate also promoted 'safe'
levels of drinking: < or = 1 and < or = 2 standard drinks/day for women and men,
respectively, among alcohol-dependent individuals. DESIGN, SETTING AND
PARTICIPANTS: In a double-blind, randomized, controlled, 12-week clinical trial
conducted in San Antonio, Texas, 75 alcohol-dependent adults received topiramate
and 75 received placebo as an adjunct to weekly standardized medication
compliance management. MEASUREMENTS: For this secondary analysis of data from
that trial, we calculated, based on self-reports, specific intervals of up to 30
days of continuous 'safe' drinking for each subject. FINDINGS: The average
longest 'safe' drinking period was 16.7 days for topiramate recipients versus 8.9
days for placebo recipients. By day 50 of treatment, 44% versus 26.4% had
achieved > or = 7 and 30.8% versus 10% had achieved > or = 14 continuous 'safe'
drinking days. Similarly, topiramate increased the relative likelihood of
continuous 'safe' drinking from 77% for > or = 7 days [relative risk (RR) for
achieving continuous 'safe' drinking = 1.77] to threefold for > or = 14 days (RR
= 3.37) and fourfold for > or = 28 days (RR = 4.07). Thus, participants who
received topiramate were more likely to achieve longer periods of 'safe' drinking
compared with those who received placebo. CONCLUSIONS: For alcohol-dependent
individuals who drank within an abstinence-oriented treatment program, topiramate
promoted 'safe' drinking. Topiramate's potential to decrease the public health
consequences of hazardous drinking needs to be established in future long-term
studies.
PMID- 17034436
TI - Bad nights or bad bars? Multi-level analysis of environmental predictors of
aggression in late-night large-capacity bars and clubs.
AB - AIMS: To clarify environmental predictors of bar-room aggression by
differentiating relationships due to nightly variations versus across bar
variations, frequency versus severity of aggression and patron versus staff
aggression. DESIGN, SETTING AND PARTICIPANTS: Male-female pairs of researcher
observers conducted 1334 observations in 118 large capacity (> 300) bars and
clubs in Toronto, Canada. MEASUREMENTS: Observers independently rated aspects of
the environment (e.g. crowding) at every visit and wrote detailed narratives of
each incident of aggression that occurred. Measures of severity of aggression for
the visit were calculated by aggregating ratings for each person in aggressive
incidents. FINDINGS: Although bivariate analyses confirmed the significance of
most environmental predictors of aggression identified in previous research,
multivariate analyses identified the following key visit-level predictors
(controlling for bar-level relationships): rowdiness/permissive environment and
people hanging around after closing predicted both frequency and severity of
aggression; sexual activity, contact and competition and people with two or more
drinks at closing predicted frequency but not severity of aggression; lack of
staff monitoring predicted more severe patron aggression, while having more and
better coordinated staff predicted more severe staff aggression. Intoxication of
patrons was significantly associated with more frequent and severe patron
aggression at the bar level (but not at the visit level) in the multivariate
analyses and negatively associated with severity of staff aggression at the visit
level. CONCLUSIONS: The results demonstrate clearly the importance of the
immediate environment (not just the type of bar or characteristics of usual
patrons) and the importance of specific environmental factors, including staff
behaviour, in predicting both frequency and severity of aggression.
PMID- 17034437
TI - Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use.
AB - AIMS: To identify early onset cannabis users by measuring basal hypothalamic
pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset
substance use when showing low activity. DESIGN: In a prospective cohort study,
adolescents who initiated cannabis use at an early age (9-12 years), those who
initiated at a later age (13-14 years) and those who did not use cannabis by the
age of 14 were compared with respect to HPA axis activity. SETTING AND
PARTICIPANTS: Data were used from the first and second assessment wave of the
TRacking Adolescents' Individual Lives Survey (TRAILS), that included 1768 Dutch
young adolescents aged 10-12 years who were followed-up across a period of 2
years. MEASUREMENTS: Cortisol was measured in saliva samples at awakening, 30
minutes later and at 8 p.m. at age 10-12. Self-reported age at first cannabis use
was used. FINDINGS: The early onset group had lower cortisol levels 30 minutes
after awakening than the late onset group (OR = 0.93, 95% CI: 0.86-0.99).
Furthermore, compared to non-users, the early and late onset cannabis users had
higher levels of cortisol at 8 p.m. (OR = 1.25, 95% CI: 1.03-1.53 and OR = 1.21,
95% CI: 1.01-1.45, respectively). CONCLUSIONS: Some evidence was found for HPA
axis hypo-activity at awakening in adolescents with early onset of cannabis use
compared to late onset users, which might indicate an increased risk for early
onset users of seeking stimulation to restore arousal levels by using substances.
PMID- 17034438
TI - Abstinence and moderate use goals in the treatment of marijuana dependence.
AB - AIMS: The purpose of this study was to examine the influence of personal goals
(abstinence or moderation) on treatment outcomes for marijuana use. Hypotheses
regarding self-efficacy for goal attainment were tested. DESIGN: Adult marijuana
users seeking treatment were assigned randomly to three treatment conditions: (1)
cognitive-behavioral relapse prevention support group; (2) individualized brief
motivational enhancement; and (3) delayed treatment control group. Follow-up
assessments were conducted at 4, 7, 13 and 16 months. SETTING: University
research offices. PARTICIPANTS: Participants were 291 adult marijuana users.
Measurements Marijuana use, personal treatment goals and self-efficacy for
achieving one's goal were assessed across the 16-month follow-up. FINDINGS:
Greater marijuana related problems and dependence symptoms were associated with
an initial goal of abstinence. Participants were more likely to achieve outcomes
consistent with their personal goals. Participants with abstinence goals reported
greater self-efficacy for goal achievement than those with moderation goals after
participating in the abstinence oriented treatment; self-efficacy for goal
success predicted goal achievement for both moderate use and abstinence goals.
CONCLUSIONS: Marijuana users approaching an abstinence-oriented treatment varied
in the extent to which they were actively seeking abstinence as the outcome.
Differences in goals were predictable from severity of problems related to use.
Goal preference and self-efficacy for achieving goals predicted outcomes. Future
research should incorporate personal goals into treatment and assess their
effects on outcomes.
PMID- 17034439
TI - Enhanced recognition of facial expressions of disgust in opiate users receiving
maintenance treatment.
AB - AIMS: Accurate recognition of facial expressions of emotion is critical in
interpersonal interaction but is impaired in alcoholics, even after a period of
abstinence. Little is known of whether other drug-dependent populations also show
these impairments. This study aimed to investigate facial expression recognition
by chronic opiate users. DESIGN: An independent group design was used to compare
20 participants receiving opiate substitution treatment, 20 ex-opiate users in
rehabilitation (average abstinence of 6 months) and 21 unemployed healthy
controls. MEASUREMENTS: The accuracy and speed of recognizing morphed emotional
facial expressions were assessed using an emotional hexagon task. FINDINGS:
Current opiate users were significantly more accurate than ex-users at
recognizing expressions of disgust. They were also generally slower than controls
in recognizing all expressions, and slower than ex-opiate users in recognizing
surprise, happy and fearful expressions. CONCLUSIONS: Opiate users in maintenance
treatment show a heightened ability to recognize facial expressions of disgust.
We suggest that this may reflect increased exposure to other people's expressions
of disgust and/or priming by the physical and social environments encountered by
opiate-dependent individuals. Further, opiate maintained individuals' global
slowness in processing emotional expressions may reflect the sedative effects of
methadone.
PMID- 17034440
TI - Cessation of injection drug use and change in injection frequency: the Chicago
Needle Exchange Evaluation Study.
AB - AIMS: To examine the effect of a needle exchange program (NEP) on incidence of
injection cessation and change in injection frequency; to explore predictors for
injection cessation and change in injection frequency; and to assess whether
injection quitters transitioned to non-injected drug use. DESIGN AND SETTING:
Between 1997 and 2002, 901 injection drug users (IDUs) were recruited from an NEP
program or an area with no NEP in Chicago, Illinois, interviewed for drug use
behaviors, tested for HIV and followed for three annual visits. All participants
were exposed to prevention services targeting HIV and drug abuse. MEASUREMENTS:
Injection cessation was defined as no injection drug use since the last
interview, and changes in the number of injections in a typical month were
examined. FINDINGS: Sixteen per cent of study participants reported stopping
injection for a median duration of 16 months, and most of them also ceased rather
than initiated the use of non-injected drugs. Those who continued injecting
reduced their injection frequency by 12% per year, on average. Independent
predictors of injection cessation were infrequent injection at baseline, younger
age and injecting with others. NEP use was not associated with injection
cessation and change in injection frequency. CONCLUSION: These results did not
support the hypothesis that NEP use influences the frequency of injection over
time. One-sixth of IDUs stopped injection for more than 1 year, providing a
substantial window for relapse prevention interventions.
PMID- 17034441
TI - Stimulant effects of 3,4-methylenedioxymethamphetamine (MDMA) 75 mg and
methylphenidate 20 mg on actual driving during intoxication and withdrawal.
AB - BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA) is currently one of the most
popular drugs of abuse in Europe. Its increasing use over the last decade has led
to concern regarding possible adverse effects on driving. The aims of the present
study were to investigate the acute effects of MDMA on actual driving performance
during the intoxication and withdrawal phase. METHODS: Eighteen recreational MDMA
users (nine males, nine females) aged 21-39 years participated in a double-blind,
placebo-controlled, three-way cross-over study. MDMA 75 mg, methylphenidate 20 mg
and placebo were administered on day 1 of treatment (intoxication phase). Driving
tests were conducted between 3 and 5 hours post-drug. Subjects returned the
following day for a repetition of the driving tests between 27 and 29 hours post
drug (withdrawal phase). On-the-road driving tests consisted of a road-tracking
test and a car-following test. Its main parameters were standard deviation of
lateral position (SDLP), time to speed adaptation (TSA), brake reaction time
(BRT) and gain. FINDINGS: MDMA and methylphenidate significantly decreased SDLP
in the road-tracking tests by about 2 cm relative to placebo on day 1
(intoxication phase). In addition, MDMA intoxication decreased performance in the
car-following test as indicated by a significant rise in the 'overshoot' of the
subjects' response to speed decelerations of the leading vehicle. Driving
performance was not affected by treatments during withdrawal on day 2.
CONCLUSION: Collectively, these data indicate that MDMA is a stimulant drug that
may improve certain aspects of the driving task, such as road-tracking
performance, but may reduce performance in other aspects of the driving task,
such as accuracy of speed adaptation during car-following performance.
PMID- 17034442
TI - Use of crystal methamphetamine among gay men in London.
AB - AIM: To examine the use of crystal methamphetamine (crystal meth) and its
association with high-risk sexual behaviour among gay men in London. DESIGN:
Cross-sectional surveys using self-administered questionnaires. SETTINGS:
National Health Service (NHS) out-patient human immunodeficiency virus (HIV)
treatment clinic in London; NHS HIV testing/sexual health clinics in London;
central London gyms. PARTICIPANTS: HIV-positive gay men attending the HIV
treatment clinic in 2002-03 (n = 388); HIV-negative gay men attending the HIV
testing/sexual health clinics in 2002-03 (n = 266); gay men using the gyms
between January and March 2003 (n = 445), 2004 (n = 653) and 2005 (n = 494).
MEASUREMENTS: Percentage of gay men who reported: (i) using crystal meth in the
previous 12 months; (ii) using other recreational drugs (e.g. cocaine, ecstasy,
ketamine); (iii) high-risk sexual behaviour in the previous 3 months. FINDINGS:
The percentage of gay men who had used crystal meth in the previous year varied
by sample (HIV treatment clinic, 12.6%; HIV testing/sexual health clinics, 8.3%;
gyms, 19.5%; P < 0.001) but did not change over time in the gyms (19.8%, 20.7%,
17.8%; P = 0.5). In all samples, the majority of men used crystal meth only once
or twice a year. Most crystal meth users (> 80%) had taken other recreational
drugs. Crystal meth and other drug users were more likely to report high-risk
sexual behaviour than other men, e.g. HIV treatment clinic sample: crystal meth
users, 34.7%; other drug users, 18.9%, non-users, 10.6%, P < 0.001. Cause and
effect could not be established. CONCLUSION: Among gay men in London surveyed in
clinics, approximately one in 10 reported using crystal meth in the previous 12
months (HIV-positive men 12.6%; HIV-negative men 8.3%). Most men used it
infrequently--only once or twice a year. There was no evidence of increasing use
of crystal meth between 2003 and 2005.
PMID- 17034443
TI - A prospective cohort study on orally administered heroin substitution for
severely addicted opioid users.
AB - AIMS: To assess the efficacy and safety of orally administered heroin
[diacetylmorphine (DAM)] tablets in substitution treatment of severely addicted
opioid users. DESIGN: An open-label, prospective cohort study with two non
randomly assigned treatment arms and historical controls: DAM tablets only versus
DAM tablets combined with injected DAM and/or other opioids, with an observation
period of 1 year. SETTING: Twenty-one out-patient treatment centres of the Swiss
heroin-assisted treatment programme. PARTICIPANTS: A total of 128 patients
received DAM tablets only, and 237 patients received a combination of orally and
intravenously applied DAM and other opioids. MEASUREMENTS: Retention rate after 1
year; number of serious adverse events; dosage of DAM over time; subjective
tolerance of study medication. FINDINGS: In the intention-to-treat analysis, 1
year retention rates after 1 year in the DAM tablets-only group [0.804, 95%
confidence interval (CI) = 0.735-0.873] as well as in the subgroup combining oral
application of DAM with intravenous application or other opioids (0.843, 95% CI =
0.797-0.889) were higher compared to historical controls (Swiss cohort of
patients who had been substituted intravenously with DAM; 1-year retention rate =
0.70). Rates of serious adverse events under study medication (tablets only =
0.038 per application year; tablets in combination = 0.028 per application year)
were comparable to the historical rate of the Swiss heroin-assisted treatment
(0.043). CONCLUSIONS: DAM tablets seem to be an effective and safe application
mode of heroin-assisted substitution treatment. Randomized clinical trials to
compare its relative efficacy to other substances are necessary.
PMID- 17034444
TI - Doping in fitness sports: estimated number of unreported cases and individual
probability of doping.
AB - AIMS: Recent studies have suggested that the use of doping substances and
particularly of anabolic androgenic steroids (AAS) is often practised by fitness
centre visitors. These studies employed direct interview techniques and
questionnaires to assess the estimated number of unreported cases of doping.
Because people hesitate to provide compromising information about themselves,
these techniques are subject to response errors. In this study we applied an
alternative interview technique to assess more accurately unreported cases of
doping in fitness centres. DESIGN AND PARTICIPANTS: The present investigation
employed the randomized response technique (RRT) to reduce response errors. A
cohort of 500 people from 49 fitness centres participated in this study. FINDING:
The RRT revealed a high prevalence of doping (12.5%). In addition, and most
importantly, the present RRT study revealed an alarmingly high prevalence of
illicit drug use, specifically of cocaine use, that has been severely
underestimated by previous studies. CONCLUSIONS: The RRT confirmed previously
estimated rates of AAS use assessed by direct interview techniques and voluntary
questionnaires, but uncovered a much higher usage rate of illicit drugs among
fitness centre visitors. This outcome enabled us to construct a 'probability'
rating for the use of doping substances in fitness centre visitors. Given its
high prevalence and the predominant use of AAS, doping among fitness centre
visitors is an issue of extreme relevance for the health care system. Our study
may help to characterize further doping substance users and to develop and apply
prevention and intervention programmes specifically to individuals at high risk.
PMID- 17034445
TI - Social influences and self-efficacy as predictors of youth smoking initiation and
cessation: a 3-year longitudinal study of vocational high school students in
Taiwan.
AB - AIMS: This 3-year longitudinal study examined changes in patterns of risk factors
and protective factors of smoking initiation and cessation among vocational high
school students in Taipei, Taiwan. DESIGN AND SETTING: In 2000, a total of 2151
10th grade students from 16 vocational high schools were assessed and followed up
in the 11th and 12th grades. Self-administered questionnaires were collected in
each year to assess the pattern of changes in smoking behaviors, and risk and
protective factors. FINDINGS: Of the 1654 non-smokers in the 10th grade, 227
students initiated smoking by the 12th grade. Higher risk factors such as peer
smoking, peers offering cigarettes, alcohol use and lower protective factors,
such as refusal self-efficacy, antismoking attitude and belief in the 10th grade
predicted youth initiation by grade 12. Increases in risk factors and decreases
in protective factors during the years from 10th to 12th grades were associated
significantly with youth smoking initiation. Of the 494 smokers in the 10th
grade, 76 students quit smoking by the 12th grade. Lower risk factors and higher
protective factors in 10th grade smokers predict youth smoking cessation by grade
12. Decreases in risk factors and increases in protective factors were associated
significantly with youth smoking cessation. CONCLUSIONS: The risk factors (i.e.
social influences) and protective factors (i.e. self-efficacy) examined in this
study predict both youth smoking initiation and youth smoking cessation.
PMID- 17034446
TI - A randomized controlled trial to assess the effects of reimbursing the costs of
smoking cessation therapy on sustained abstinence.
AB - AIMS: We studied whether reimbursement for smoking cessation treatment (SCT) can
increase prolonged abstinence from smoking up to 2 years. SETTING, PARTICIPANTS
AND DESIGN: From the general population, we recruited smokers and assigned them
randomly to a control group (n = 634) or an intervention group (n = 632). For 6
months, participants in the intervention group could apply for reimbursement and
received information regarding the reimbursed SCT. Participants in the control
group received no reimbursement or information. MEASUREMENTS: In this follow-up
study, prolonged abstinence from smoking was defined as reported being abstinent
from at least 7 days before the end of reimbursement until the follow-up
assessment 6 months or 2 years later. FINDINGS: At 6 months after the end of
reimbursement, 18 participants in the control group (2.8%) and 35 participants
(5.5%) in the intervention group reported sustained abstinence for at least 6
months [odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.1-3.6]. Two years
after the reimbursement period, 10 participants in the control group (1.6%) and
27 participants in the intervention group (4.3%) still reported sustained
abstinence (OR = 4.1, 95% CI 1.7-10.2). The overall effectiveness of SCT
increased with reimbursement and was 22% in the intervention group and 8% in the
control group after 2 years. CONCLUSIONS: Reimbursement may be an effective
strategy to increase the prolonged abstinence rate even after 2 years.
PMID- 17034447
TI - Addiction to apomorphine: a clinical case-centred discussion.
AB - AIM: To report the case of a patient, who in the context of an anti-Parkinsonian
therapy, developed addiction to apomorphine. METHODS: Clinical case description.
RESULTS: Apomorphine is a dopaminergic agonist that acts directly on D2
receptors. It has been used in alcoholism, male sexual dysfunction and with
diagnostic and therapeutic purposes in Parkinson's disease (PD). CONCLUSIONS: The
present work describes the case of a woman with PD who developed a loss of
control over the consumption of apomorphine that resulted in a significant
impairment of her functioning. PD patients with high frequency develop different
psychiatric symptoms. Conversely, anti-Parkinsonian drugs also generate
psychiatric symptoms that can be experienced by the patient as pleasant
sensations ('alerting', 'awakening', 'activating', hypomania and hypersexuality).
In spite of this, addiction to these drugs in patients with PD is a very rare
phenomenon. Currently, the prescription of apomorphine has been extended to
patients with erectile dysfunction, which may increase the prevalence of
addiction cases or of severe psychiatric symptoms.
PMID- 17034448
TI - Designer drugs as a cause of homicide.
PMID- 17034449
TI - Canadian heroin supply and the Australian 'heroin shortage'.
PMID- 17034462
TI - Biologic agents in psoriasis.
AB - This paper reviews the new biologic agents that selectively block the immunologic
steps implicated in the pathogenesis of psoriasis. Four strategies have been
targeted: reduction of the number of pathogenic T cells; inhibition of T-cell
activation and migration; modulation of the immune system; and blockage of the
activity of inflammatory cytokines. There are three classes: monoclonal
antibodies, fusion proteins and recombinant cytokines or growth factors. The
actions, efficacy and side-effect profile of the biologic agents, alefacept,
efalizumab, etanercept and infliximab, are reviewed.
PMID- 17034463
TI - Non-Hodgkin lymphoma and skin cancer: A dangerous combination.
AB - There is a significant association between non-Hodgkin lymphoma, including
chronic lymphocytic leukaemia, and both melanoma and non-melanoma skin cancer.
This review highlights the existing data on the phenomenon of accelerated skin
cancer in patients with non-Hodgkin lymphoma and specifically chronic lymphocytic
leukaemia. The outcomes of patients with non-Hodgkin lymphoma (including chronic
lymphocytic leukaemia) and non-melanoma skin cancer are worse than in patients
without concomitant lymphoreticular malignancy, as shown by increased rates of
local recurrence, regional metastasis and death. Pathogenic factors may be common
between non-Hodgkin lymphoma and chronic lymphocytic leukaemia and skin cancer.
The treatment of skin cancer in patients with non-Hodgkin lymphoma must factor in
the worse prognosis and adapt standard therapeutic approaches to minimize the
risk of metastasis and death. Preventive strategies and early detection are
paramount in this high-risk population.
PMID- 17034464
TI - Development of a psychological treatment service for pruritic skin conditions.
AB - The role of psychological contributions to common dermatological disease is
increasingly recognized. It is often a challenge to find suitable psychological
services to complement dermatological treatment. This paper describes the
development of a psychological treatment service to reduce scratching behaviour
found in common pruritic skin conditions. Our Department of Dermatology together
with a consultation-liaison psychiatrist designed a four-session outpatient
treatment programme incorporating psychiatric assessment, psychoeducation about
the itch-scratch cycle, behavioural analysis, habit reversal techniques and
between-session tasks for the patient to complete. This programme is actively
modified in consultation with patients and their therapists to suit each
patient's individual needs. Formal investigation is required to determine if this
psychological treatment adds benefit in overall symptom control beyond
dermatological treatment alone.
PMID- 17034465
TI - Segmental haemangiomas of infancy: A review of 14 cases.
AB - Haemangiomas of infancy are the commonest benign tumour in childhood, with the
majority being a localized subtype, only requiring therapy in specific locations.
The segmental subtype, however, confers a higher complication rate, an
association with the PHACE syndrome and poorer prognosis. This retrospective case
series of 14 infants with segmental haemangiomas aimed to further define the
variety of clinical presentations, complication rates, and response to treatment
in this subset of patients. We found in our series that 71% of infants with
segmental haemangiomas develop at least one complication related to the lesion.
Systemic corticosteroids prevented the further growth as well as reduced the pain
and ulceration of the segmental haemangiomas in all of those treated. Early
recognition and early treatment to arrest the growth of segmental haemangiomas
will reduce morbidity and complications associated with these haemangiomas.
Corticosteroid use, however, needs to be considered against the high incidence of
side-effects such as secondary hypertension (40%), cushingoid features (40%) and
growth suppression (67%). In our experience, these infants benefit from
multidisciplinary team involvement for the assessment of associated syndromes,
and to follow up and avoid complications associated with systemic therapy.
PMID- 17034466
TI - Retrospective 5-year review of 131 patients with mycosis fungoides and Sezary
syndrome seen at the National Skin Centre, Singapore.
AB - A total of 131 new cases of mycosis fungoides and Sezary syndrome were diagnosed
clinically and histopathologically at our centre over a 5-year period. There were
87 males and 44 females with a mean age of 36.3 years (range 3-87 years) and no
racial predilection. Of the 62 patients (47.3%) with classical mycosis fungoides,
the majority were male (male : female = 4.2:1). There was one patient with Sezary
syndrome. Patients aged older than 50 years were more likely to present with a
longer duration of symptoms and advanced disease. In contrast to classical
mycosis fungoides, the 47 patients diagnosed with hypopigmented mycosis fungoides
had early stage disease, were younger, and no gender predilection was noted. The
mean duration of follow up was 19.7 months (range 0.2-54.8 months). Complete
remission was achieved in 24.7% and 53.8% of patients followed up at 1 and 3
years, respectively, using skin-directed and systemic treatment modalities
appropriate for the stage of disease. There were five patients with progressive
disease and three patients with advanced disease who died from disease-related
complications. The most significant prognostic factors for 1-year and 3-year
outcomes were the patient's duration of symptoms and stage of disease at
presentation.
PMID- 17034467
TI - Leg crossers' dimple: A form of localized lipoatrophy.
AB - We report eight individuals with localized lipoatrophy of the lateral lower leg
that were seen by a single dermatologist in a 1-year period. All were
asymptomatic and half had mild epidermal changes consistent with lichenification.
Seven were an incidental finding during a general skin examination. All had a
long-standing history of frequent leg crossing. The sites correlated with the
area resting on the patella of the opposing knee. The depressions were larger on
sides of leg-crossing preference. Only one had a significant rise in antinuclear
antibodies, but this patient had no other clinical or serological abnormalities.
This appears to be an extremely common yet previously unreported form of
localized lipoatrophy.
PMID- 17034468
TI - Two-year interim results from a 5-year study evaluating clinical recurrence of
superficial basal cell carcinoma after treatment with imiquimod 5% cream daily
for 6 weeks.
AB - Imiquimod 5% cream is approved in the USA, Europe and Australia to treat
superficial basal cell carcinoma, using a regimen of once daily, 5 times per week
for 6 weeks. Vehicle-controlled, phase III clinical trials show that imiquimod is
safe and effective for treating superficial basal cell carcinoma with dosing 5 or
7 times per week for 6 weeks. This phase III, open-label study evaluates the long
term (5 years) clinical efficacy and safety of dosing once daily, for which this
manuscript reports the 2-year time point in the follow-up period. For the 169
enrolled subjects, the tumour selected for treatment was assessed clinically to
determine initial clearance at the 12-week post-treatment visit. If clinically
clear of superficial basal cell carcinoma, subjects entered a 5-year, long-term
follow-up period. Subjects were evaluated for recurrence at the 3-, 6-, 12- and
24-month follow-up visits. The initial clearance rate at 12 weeks post treatment
was 94.1%. The proportion of subjects who were clinically clear at the 2-year
follow-up visit was estimated to be 82.0%. Imiquimod was tolerated when applied
daily, with erythema reported for all subjects participating in the study. The
recurrence rate observed suggests that once daily dosing and 5x/week dosing yield
similar clearance rates, but daily dosing increases local skin reactions.
PMID- 17034469
TI - Muir-Torre syndrome: Diagnostic and screening guidelines.
AB - A 65-year-old man presented with a history of multiple skin coloured papules on
his face that were asymptomatic. He had an adenocarcinoma resected from his
proximal colon 12 years prior to presentation as well as a family history of
colon cancer on the maternal side. Diagnostic biopsies showed the lesions to be
sebaceous adenomas and epitheliomas and the diagnosis of Muir-Torre syndrome was
made. The sebaceous tumour tissue showed microsatellite instability and
immunohistochemical staining indicated diminished expression in the DNA mismatch
repair protein complex MSH2/MSH6. Genetic analysis showed a germline mutation in
the MSH2 gene confirming the diagnosis of Muir-Torre syndrome. The patient and
his first-degree relatives have been referred for genetic counselling and
screening. We review the diagnostic criteria in this syndrome and review the
recommended screening guidelines.
PMID- 17034470
TI - Allopurinol induced generalized eosinophilic pustular folliculitis.
AB - A 71-year-old Cambodian man who was commenced on allopurinol for the treatment of
gout developed a generalized papulopustular follicular eruption 8 weeks following
introduction of the drug. The skin biopsy findings were consistent with that of
eosinophilic pustular folliculitis. Resolution of the rash took place during the
8 weeks following cessation of allopurinol and treatment with oral and topical
corticosteroids.
PMID- 17034471
TI - The syndrome of hereditary leiomyomatosis and renal cell cancer (HLRCC): The
clinical features of an individual with a fumarate hydratase gene mutation.
AB - A 55-year-old woman presented with multiple cutaneous leiomyomas and multiple
uterine leiomyomas (fibroids). The clinical diagnosis of the autosomal dominant
hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome was confirmed by
identification of a fumarate hydratase gene mutation. This case highlights the
need to consider the possibility of renal and uterine cancer in members of
cutaneous leiomyomatosis families.
PMID- 17034472
TI - Metastatic Bowen carcinoma.
AB - A 72-year-old man presented with basaloid squamous cell carcinoma metastatic to
both lungs that was morphologically similar to recurrent, invasive moderately to
poorly differentiated carcinoma arising from persistent Bowen's disease of the
right cheek. The original lesion of invasive moderately differentiated squamous
cell carcinoma arising in Bowen's disease had been excised 11 years previously.
Mohs' surgery was performed for the recurrent lesion on the cheek 12 months prior
to detection of lung metastases. He died of respiratory failure 19 months
following diagnosis of his metastatic disease. Our case reflects the potentially
aggressive nature of invasive squamous cell carcinoma arising from Bowen's
disease and highlights the importance of approaching this entity with a view to
complete surgical excision with adequate margins.
PMID- 17034473
TI - Successful treatment of recalcitrant necrotizing eosinophilic folliculitis using
indomethacin and cephalexin.
AB - A 56-year-old man presented with a 4-month history of a painful and pruritic
eruption consisting of crusted plaques and blisters on his face, scalp and chest.
The patient suffered from headaches and malaise but was afebrile. Two skin
biopsies revealed an epidermis which was eroded and covered by locules of serum
and neutrophils. In the underlying dermis, there was a marked mixed inflammatory
reaction including lymphocytes, neutrophils and numerous eosinophils. There was
exocytosis of eosinophils into several follicles with areas of follicular
mucinosis. A diagnosis of necrotizing eosinophilic folliculitis was made based
upon the clinical and histopathological findings. The diagnosis was supported by
the rapid response to a combination of indomethacin and cephalexin. The patient
has taken continuous indomethacin (with rabeprazole and misoprostol cover) and
cephalexin for 2 years. If treatment is withdrawn he experiences a flare of his
disease within 2 weeks. This case highlights the potentially chronic nature of
this disease.
PMID- 17034474
TI - Parvovirus B19 infection presenting as 'bathing trunk' erythema with pustules.
AB - A 7-year-old girl presented with acute vulval erythema and pustules, associated
with a petechial eruption in her flexures and over her feet. There was a mild
prodromal illness and the patient was afebrile. There were minimal symptoms
associated with the rash. Skin and throat swabs were negative and blood
examination showed mild neutrophilia and lymphopaenia. Parvovirus B19 IgM was
detected on serology and cutaneous features resolved within 4 days. This is a
further case of parvovirus B19 infection presenting as a 'bathing trunk' exanthem
that has unique dermatologic features, including the presence of pustules and
distant petechiae.
PMID- 17034475
TI - Prurigo pigmentosa.
AB - A 22-year-old Chinese woman presented with a 5-year history of an intensely
pruritic eruption on her posterior neck, mid back and sacrum leaving reticulate
pigmentation. The diagnosis of prurigo pigmentosa was made on the basis of the
clinico-histological features and a response to minocycline. Although prurigo
pigmentosa is uncommon, it has characteristic clinical and histological features.
Early diagnosis and appropriate treatment result in a rapid response and prevents
a progression of pigmentation.
PMID- 17034476
TI - Primary cutaneous diffuse leiomyosarcoma with desmoplasia.
AB - A 65-year-old man presented with an indurated plaque over his left cheek and left
neck. An initial punch biopsy of skin showing increased smooth muscle bundles was
consistent with a diagnosis of smooth muscle hamartoma. A second incisional skin
biopsy revealed a well-differentiated smooth muscle proliferation invading into
the dermis and subcutaneous fat in a diffusely infiltrative pattern and with a
desmoplastic component, suggesting a diagnosis of desmoplastic leiomyosarcoma.
Resection of the tumour confirmed the presence of a cytologically low grade
leiomyosarcoma with an insidious infiltrative growth pattern. This rare pattern
of diffuse leiomyosarcoma is important to recognize as the histological features
are subtle and may potentially constitute a pitfall in histological diagnosis in
a small biopsy specimen. In addition, our case illustrates overlapping morphology
between diffuse and desmoplastic types of leiomyosarcoma.
PMID- 17034477
TI - Chondrocutaneous advancement flap for reconstruction of helical rim defects in
dermatologic surgery.
AB - The helical rim is often affected with cutaneous malignancies and requires
special attention in the repair, owing to the complex cartilaginous contour,
preservation of the aesthetic contour and restoration of its supportive function
for eyeglasses and hearing aids. We review the surgical technique of
chondrocutaneous advancement flap described by Antia and Buch as one of the most
cosmetically appealing and versatile approaches for the repair of small defects
of the ear helix.
PMID- 17034478
TI - Cheilitis caused by contact allergy to anethole in spearmint flavoured
toothpaste.
AB - A 63-year-old woman presented with a 6-year history of persistent cheilitis.
Minimal improvement was achieved with therapeutic measures. Patch testing was
positive to anethole, a flavouring used in her toothpaste. Her cheilitis resolved
after cessation of the flavoured toothpaste. This case demonstrates the
importance of considering contact allergy to toothpaste flavours in patients with
cheilitis.
PMID- 17034489
TI - Development of a cell-isolation method for human prostatic smooth muscle cells
based on cell type-specific activation of the SM22 gene promoter.
AB - OBJECTIVE: To separate smooth muscle cells (SMCs) from fibroblasts in cultured
human prostatic stromal cells (PrSCs) by characterizing the SM22 promoter as a
prostatic SMC-specific gene promoter, and to investigate its use for a promoter
based cell-sorting method, as SMCs are critical for stromal function and the
pathological changes in the development of benign prostatic hyperplasia.
MATERIALS AND METHODS: Human PrSCs were cultured in SMC-selective medium or
standard medium, respectively, to obtain typical cultures of SMCs and
fibroblasts. SM22 promoter activity and specificity were analysed by luciferase
reporter-gene assay. A dual-colour vector was constructed with the expression of
the red fluorescent protein (RFP) under the control of the 1.4 kb SMC-specific
SM22 promoter, and the expression of the green fluorescent protein (GFP) under
cytomegalovirus promoter. Fluorescence-activated cell sorting (FACS) was used to
isolate and enrich GFP+/RFP+ and GFP+/RFP- cells. Cell phenotype was confirmed by
reverse transcription-polymerase chain reaction and immunofluorescence. RESULTS:
The 1.4 kb SM22 promoter activity was much higher in PrSCs cultured in SMC
selective medium. Immunofluorescence staining and merged fluorescence microscopy
ensured that SM22 promoter-driven GFP positive cells were SMCs. After
transfection of the dual-colour vector into PrSCs, GFP+/RFP+ cells (SMCs) and
GFP+/RFP- cells (fibroblasts) were isolated by FACS. The phenotype of FACS
enriched SMCs and fibroblasts was confirmed. CONCLUSION: These results indicate
that the 1.4 kb SM22 promoter is specific for prostatic SMCs. This dual-colour
vector could be a useful tool for separating living SMCs from fibroblasts using
FACS.
PMID- 17034490
TI - Sigmoid orthotopic neobladder after radical cystectomy for bladder tumour: an
Indian experience.
AB - OBJECTIVE: To determine the long-term results of constructing a sigmoid
neobladder after radical cystectomy for transitional cell carcinoma (TCC) of the
urinary bladder. PATIENTS AND METHODS: The study included 170 patients with TCC
of the bladder and a normal sigmoid colon. After radical cystectomy the
neobladder was formed by completely detubularizing an isolated sigmoid colon
segment. Subsequently patients were followed by clinical, biochemical,
radiological and urodynamic assessments. RESULTS: Four patients died soon after
surgery; the neobladder-related delayed complications were death in three
patients, loss of five renal units, and electrolyte imbalance in five patients.
Uretero-intestinal anastomotic narrowing was another frequent delayed
complication. Most (97%) patients had nocturnal incontinence, and most voided
with a good stream with a minimal postvoid residual urine volume. CONCLUSION: The
sigmoid neobladder, despite some limitations, is the best option for diverting
urine after radical cystectomy.
PMID- 17034491
TI - Could a rural lifestyle decrease the prevalence of erectile dysfunction?
AB - OBJECTIVE: To determine the prevalence of erectile dysfunction (ED) in a specific
population and explore potential correlates with lifestyle. SUBJECTS AND METHODS:
This prospective observational study, covering a population of a very small rural
town, included 2000 men aged > or = 20 years from a total population of 121 831
(51% female and 49% male). The International Index of Erectile Function was
completed by each of the 2000 men at their homes over a 1-year period. Another
questionnaire assessing socio-economic status and health-related determinants of
ED were also completed. RESULTS: All 2000 men completed the questionnaires;
overall, only 34 reported ED (1.7%). The frequency of mild, mild to moderate,
moderate and severe ED was 12%, 29%, 20% and 38%, respectively. Significantly
more men aged > 51 years had ED than those aged <41 years (0.05% and 0.45%,
respectively; P < 0.001). There was no difference in ED with salary levels.
CONCLUSION: The prevalence of ED in this particular rural population of Brazil
was very low, at only 1.7%. Although ED increases with age, this association was
not apparent for all age groups. It seems that several others factors, e.g.
lifestyle, culture and diet, could be important for the onset of ED.
PMID- 17034492
TI - Sperm banking: use and outcomes in patients treated for testicular cancer.
AB - OBJECTIVE: To identify the frequency that sperm banking was used by men being
treated for testicular cancer at our institution, and to characterize the
differences between men choosing to bank sperm or not, and outcomes in terms of
after-treatment pregnancies. PATIENTS AND METHODS: A questionnaire addressing
sperm banking and fertility was administered to men treated for testicular cancer
at our institution between 1994 and 2004; the results were evaluated
statistically. RESULTS: Overall, 31 of 129 (24%) respondents had banked sperm. Of
these, two had used their banked sperm to father a child, and 12 had had children
naturally. Men who banked sperm were a mean of 10.3 years younger (P < 0.001) and
less likely to have children at the time of diagnosis (P < 0.025) than men
choosing not to bank sperm. The cost of banking sperm was reported to include a
mean fee of US dollars 358 (median 300, range 0-1000), and a mean annual
maintenance fee of US dollars 243.86 (median 300, range 0-1200). CONCLUSIONS:
Only a minority of men in this study chose to bank sperm (24%). Among those who
did, the use of banked sperm was low (<10%), and many men could have children
without using banked sperm. Given the relatively high costs of sperm banking and
the low rate of sample use, patients should be counselled on the costs and
benefits of sperm banking before treatment for testicular cancer.
PMID- 17034493
TI - Three-dimensional ultrasonography of the urinary bladder: preliminary experience
of assessment in patients with haematuria.
AB - OBJECTIVE: To assess the value of three-dimensional (3D) vs two-dimensional (2D)
ultrasonography (US) in the diagnostic evaluation of the urinary bladder in
patients with haematuria. PATIENTS AND METHODS: In all, 42 patients with painless
haematuria and/or irritative voiding symptoms were examined with 2D- and 3D-US.
US was done with an Acuson Sequoia unit (Siemens Medical Sol. Mountain View, CA,
USA) and the Perspective(R) 3D technique, to assess the presence of bladder
lesions, including bladder cancer, bladder wall hypertrophy with trabeculation
and diverticula, mucosal bladder folds or re-growth of the prostate mimicking a
bladder tumour. The imaging findings were compared with cystoscopy and/or bladder
biopsy. RESULTS: In 21 of the 42 patients (50%) cystoscopy with bladder biopsy
revealed bladder cancer. Overall, 3D-US gave a correct diagnosis for 36 of 42
patients (86%). All 21 bladder cancers were correctly diagnosed, and 15 (71%) of
the 21 benign bladder lesions were correctly identified. By contrast, 2D-US
findings gave suspected bladder cancer in all patients. CONCLUSIONS: 3D-US is
significantly more accurate than standard 2D-US in the diagnostic evaluation of
patients with haematuria. Thus, this diagnostic technique might be useful for
routine evaluation of the urinary bladder.
PMID- 17034494
TI - Melatonin rhythm in children with enuresis.
AB - OBJECTIVE: To study the circadian rhythm of melatonin in children with enuresis.
PATIENTS AND METHODS: Twenty-five children, divided into two groups (enuretic
patients and controls) were assessed; salivary samples were collected to measure
melatonin by radioimmunoassay using commercial kits. Friedman two-way anova and
Wilcoxon tests were used to assess the circadian rhythm of melatonin, and anova
with between-patient factors and Mann-Whitney tests to compare melatonin values
and groups. RESULTS: Both groups had statistically significant differences in
melatonin concentration during the 24-h period (both P < 0.001), with a circadian
rhythm; the highest values were always at approximately 04.00 hours. There were
no significant differences overall in melatonin values between cases and
controls, but patients had lower peak values than controls at 04.00 hours, and
higher melatonin levels at 24.00 hours, but with no significant differences.
CONCLUSION: There was some evidence for minor disturbances in the circadian
rhythm of melatonin as a cause of enuresis, but the rhythm was not grossly
disrupted.
PMID- 17034495
TI - Effect of chronic lithium administration on endothelium-dependent relaxation of
rat corpus cavernosum: the role of nitric oxide and cyclooxygenase pathways.
AB - OBJECTIVE: To verify the effect of chronic lithium administration on the
endothelium-dependent relaxation of rat corpus cavernosum, as lithium is a major
drug for treating bipolar disorder and some studies showed that lithium might
cause erectile dysfunction in such patients, by a mechanism as yet unknown.
MATERIALS AND METHODS: LiCl (600 mg/L) was dissolved in drinking water and
Sprague-Dawley rats received the solution for 30 days; control rats received tap
water. After 30 days corporeal strips were prepared from both groups, mounted
under tension in oxygenated organ baths, and pre-contracted with phenylephrine
(7.5 microm). After equilibration, the strips were relaxed by acetylcholine (10
nm to 1 mm) in the presence or absence of indomethacin (a cyclooxygenase
inhibitor; 20 microm). Furthermore, the relaxant responses to sodium
nitroprusside (1 nm to 1 mm), a nitric oxide (NO) donor, were investigated in
both groups. NADPH-diaphorase histochemistry was used to identify NO synthase
within cavernosal tissue strips of both groups. RESULTS: The acetylcholine
dependent relaxation was significantly lower in lithium-treated rats than in
controls. Although indomethacin decreased significantly the relaxant responses to
acetylcholine in controls, it increased the relaxant responses in lithium-treated
rats. NADPH-diaphorase staining was greater in the chronic lithium-treated than
in control preparations. Sodium nitroprusside produced similar relaxation in both
groups. CONCLUSION: Chronic lithium administration can impair the endothelium
dependent relaxation of rat corpus cavernosum; NO availability might decrease
after lithium administration and the cyclooxygenase pathways might have a role in
this effect.
PMID- 17034496
TI - Palliative transurethral resection of the prostate: functional outcome and impact
on survival.
AB - OBJECTIVE: To assess the long-term functional and oncological outcome in a
consecutive series of patients undergoing palliative transurethral resection of
the prostate (pTURP). PATIENTS AND METHODS: We retrospectively assessed all
patients who had a pTURP between 1992 and 2004 at our institution. Patients with
incidental prostate cancer (pT1a/pT1b) were excluded. In all, 89 patients (mean
age 75.9 years, sd 0.9, at diagnosis) entered the study. RESULTS: The median
(range) prostate-specific antigen level at diagnosis was 25.7 (0.7-5000) ng/mL
and the mean Gleason score was 7. The mean (sd, range) interval between the
diagnosis of prostate cancer and pTURP was 1.5 (0.3, 0.5-10.9) years. The
indications for pTURP were refractory urinary retention in 30%, severe bladder
outlet obstruction with a postvoid residual urine volume of > 100 mL in 43%, and
bladder stones, haematuria and hydronephrosis in 9% each. The mean (sd, range)
follow-up after pTURP was 2.6 (0.2, 0.1-7.3) years. The peri-operative mortality
(<30 days) was 2%, and 22 patients (25%) died during the follow-up. As estimated
by Kaplan-Meier analysis, the 1-, 2- and 5-year survival rates were 83%, 70% and
61%, respectively. Patients with prostate cancer in the pTURP specimen had a
shorter 3-year survival (52%) than those with a negative histology (89%, P =
0.03). At the last follow-up, 79% of men voided spontaneously and were continent.
A repeat pTURP was necessary in 25% of patients, 11% required permanent
catheterization and 10% were incontinent. CONCLUSION: Despite greater peri
operative mortality and morbidity than conventional TURP, pTURP is a fairly safe
and effective procedure. Although a potential negative impact of pTURP on
survival cannot be excluded, the estimated 5-year survival of 61% in this series
seems to justify this intervention.
PMID- 17034497
TI - Functional urinary and fecal incontinence in neurologically normal children:
symptoms of one 'functional elimination disorder'?
AB - OBJECTIVE: To clarify the relationship between disordered defecation and non
neuropathic bladder-sphincter dysfunction (NNBSD) by comparing the prevalence of
symptoms of disordered defecation in children with NNBSD before and after
treatment for urinary incontinence (UI), and assessing the effect of such
symptoms on the cure rate for UI. PATIENTS AND METHODS: In the European Bladder
Dysfunction Study, a prospective multicentre study comparing treatment plans for
children with NNBSD, 202 children completed questionnaires on voiding and on
defecation, at entry and after treatment for UI. Four symptoms of disordered
defecation were evaluated; low defecation frequency, painful defecation, fecal
soiling, and encopresis. RESULTS: At entry, 17 of the 179 children with complete
data sets had low defecation frequency and/or painful defecation (9%), classified
as functional constipation (FC). Of the 179 children, 57 had either isolated
fecal soiling or soiling with encopresis (32%), classified as functional fecal
incontinence (FFI). After treatment for UI, FFI decreased to 38/179 (21%)
(statistically significant, P = 0.035); for FC there were too few children for
analysis. After treatment for UI, 19 of the 179 children (11%) reported de novo
FFI. Symptoms of disordered defecation did not influence the cure rate of
treatment for UI. CONCLUSIONS: FFI improved significantly after treatment for UI
only, but not in relation to the outcome of such treatment. FFI did not influence
the cure rate for UI. There was little to support a causal relation between
disordered defecation and NNBDS ('functional elimination syndrome').
PMID- 17034498
TI - Prevalence and correlations of lower urinary tract symptoms, erectile dysfunction
and incontinence in men from a multiethnic Asian population: Results of a
regional population-based survey and comparison with industrialized nations.
AB - OBJECTIVE: To determine, in a population-based survey, the prevalence of lower
urinary tract symptoms (LUTS), erectile dysfunction (ED) and incontinence in
community-dwelling men in multiethnic Malaysia, as currently available Western
demographic data might not be applicable in the Asian population. SUBJECTS AND
METHODS: A cross-sectional population-based survey was carried out in the State
of Penang, Malaysia, with a target population of men aged > or = 40 years. Using
a multistage study design, random systematic sampling was used to represent the
target population, who were weighted based on ethnicity and rural-urban ratios so
as to represent the general population distribution. Trained field-workers
conducted direct interviews and administered the American Urological Association
Symptom Index (AUA-SI), the International Index of Erectile Function (IIEF-5)
questionnaire and questions on incontinence based on the International Continence
Society 2002 definition. RESULTS: In all, 418 men aged > or = 40 years were
interviewed, of whom 353 completed the AUA-SI questionnaire (84.5% response
rate). The prevalence of mild, moderate and severe LUTS was 80.6%, 6% and 0.3%,
respectively. The prevalent symptoms were frequency and nocturia. There was
moderate and severe ED in 45.9% of men, whereas incontinence was reported by
8.2%. The AUA-SI correlated strongly with age (R = 0.291, P < 0.001), IIEF-5 (R =
- 0.265, P < 0.001) and diabetes mellitus. CONCLUSION: The prevalence and
severity of LUTS, ED and incontinence increased with age in this multiethnic
Asian population, in which ED correlated strongly with LUTS. Compared to the
Western population, the prevalence of LUTS was significantly lower, while the
prevalence of ED and incontinence were comparable.
PMID- 17034499
TI - High-intensity focused ultrasound for treating prostate cancer.
PMID- 17034500
TI - Different brain effects during chronic and acute sacral neuromodulation in urge
incontinent patients with implanted neurostimulators.
AB - OBJECTIVE: To compare changes in regional cerebral blood flow (rCBF), using
positron emission tomography (PET), during chronic and acute sacral
neuromodulation (SN). SN is an effective long-term treatment for chronic urge
incontinence due to urinary bladder hyperactivity, as sensory nerves, spinal and
supraspinal structures are probably responsible for the action of SN. It is not
known which brain areas are involved, and the optimum benefit of SN is not
immediate, suggesting that induced plasticity of the brain is necessary. PATIENTS
AND METHODS: Brain activity was measured in two groups: 12 urge incontinent
patients (11 women and one man; mean age 52 years) in whom an implanted
unilateral S3 nerve neurostimulator had been effective for >6 months (mean time
after implantation 4.5 years); and eight urge incontinent patients (seven women
and one man; mean age 49 years) in whom the neurostimulator was activated for the
first time in the PET scanner. RESULTS: During SN in chronically implanted
patients, there were significant decreases in rCBF in the middle part of the
cingulate gyrus, the ventromedial orbitofrontal cortex, midbrain and adjacent
midline thalamus, and rCBF increases in the dorsolateral prefrontal cortex.
During acute SN in newly implanted patients, there were significant decreases in
rCBF the medial cerebellum, and increases in the right postcentral gyrus cortex,
the right insular cortex and the ventromedial orbitofrontal cortex. Group
analysis between chronic and newly implanted patients showed significant
differences in the associative sensory cortex, premotor cortex and the
cerebellum, all three involved in learning behaviour. CONCLUSIONS: These findings
suggests that chronic SN influences, presumably via the spinal cord, brain areas
previously implicated in detrusor hyperactivity, awareness of bladder filling,
the urge to void and the timing of micturition. Furthermore, SN affects areas
involved in alertness and awareness. Acute SN modulates predominantly areas
involved in sensorimotor learning, which might become less active during the
course of chronic SN.
PMID- 17034501
TI - Biochemical (prostate-specific antigen) relapse-free survival and toxicity after
125I low-dose-rate prostate brachytherapy.
AB - OBJECTIVE: To report our clinical experience and 5-year prostate-specific antigen
(PSA) relapse-free survival rate for early-stage prostate cancer after (125)I low
dose-rate prostate brachytherapy. PATIENTS AND METHODS: In all, 300 patients were
treated between March 1999 and April 2003, and followed prospectively. Patients
were stratified into low-, intermediate- and high-risk groups, and those
receiving neoadjuvant androgen deprivation (NAAD) or not. Kaplan-Meier estimates
of PSA relapse-free survival and PSA nadirs were obtained for all patients and
for the risk groups. Toxicity, as urinary and erectile dysfunction (ED), were
reported from a prospective database. RESULTS: The median (range) follow-up was
45 (33-82) months. The actuarial PSA relapse-free survival was 93% at 5 years; 21
(7%) of patients had evidence of biochemical failure as defined by the American
Society of Therapeutic Radiation Oncology criteria. There was no significant
difference in actuarial survival for patients in the different risk groups, or
between those receiving NAAD or not (low-risk 96%, intermediate 89%, high 93%, P
= 0.12; NAAD 92%, no NAAD 95%, P = 0.30). Overall the 3-year median PSA level was
0.3 ng/mL (192 men). There was no significant difference in median 3-year PSA
levels for different risk groups, or for those treated with or with no NAAD. The
3- and 4-year PSA nadir of <0.5 ng/mL was achieved by 71% and 86% of men,
respectively. The acute urinary retention rate was 7%; 5.6% of men developed
urethral strictures requiring dilatation, while 2.7% required a transurethral
resection of the prostate after implantation, for obstructive symptoms. Of
patients with no ED before treatment, 62% had no ED at 2 years, and of these 60%
used a phosphodiesterase inhibitor. CONCLUSION: This prospective series confirms
the excellent overall biochemical survival after (125)I brachytherapy; the
treatment was tolerated well, with early and late urinary toxicity and ED similar
to other published results.
PMID- 17034502
TI - Growth curves of the fetal prostate based on three-dimensional reconstructions: a
correlation with gestational age and maternal testosterone levels.
AB - OBJECTIVE: To create a nomogram of the fetal growth of the human prostate
corresponding to gestational age, and to investigate the relationship between the
expansive growth of the fetal prostate and the maternal testosterone surge during
pregnancy. MATERIALS AND METHODS: In all, 27 fetal prostates at 11-40 weeks of
gestation, and seven neonatal specimens at 1-20 weeks after birth, were analysed.
Serial sections of prostates were immunostained and examined using light
microscopy. After modular image acquisition the volumes were calculated using
three-dimensional reconstruction. The prostate volumes were correlated with
gestational age, and related to reference testosterone levels during pregnancy.
RESULTS: There was exponential growth of the fetal prostate with gestational age.
The increasing volume of the prostate during the fetal period corresponded with
maternal testosterone levels. In the second trimester there was a significant
increase in prostate volume in relation to the bladder. In infants,
macroscopically there was an inverse proportion between bladder size and prostate
volume. CONCLUSIONS: Starting from the second trimester there is distinct growth
of the fetal prostate, obviously triggered by the maternal testosterone surge. In
neonates there is an inversion of the dimensions between bladder and prostate.
These results indicating exponential growth of the fetal prostate provide
evidence of a gender-related transient infravesical obstruction in human fetuses.
PMID- 17034503
TI - The use of prostate-specific antigen testing in men presenting with haematuria.
AB - OBJECTIVES: To analyse prostate-specific antigen (PSA) levels and clinical
outcome in men presenting with haematuria, to develop an evidence-base for the
use of PSA testing in this setting, as haematuria is a known complication of
locally invasive prostate cancer, and so PSA levels are often measured in
patients presenting with haematuria. PATIENTS AND METHODS: We reviewed the
records of 637 men presenting with haematuria to our urology department between
April 2002 and June 2005. RESULTS: Of 373 men aged 50-79 years, 278 (75%) had
their PSA level measured, and 50 were abnormal. Prostate biopsies were taken in
27 men with an abnormal PSA level (54%) and one man with a normal PSA level but
an abnormal digital rectal examination. Prostate cancer was detected in 22
patients (8% of those tested, and 71% of those biopsied); 4.7% of all men
presenting with macroscopic haematuria and aged 50-79 years were found to have
prostate cancer, vs 8.5% of those with microscopic haematuria. CONCLUSIONS: We
report a higher proportion of prostate cancers in men presenting with haematuria
and aged 50-79 years than reported in previous screening studies, and a cancer
detection rate of 71% of those biopsied, which is at least double the detection
rates seen in screening studies. In the absence of a prospective controlled
trial, PSA testing will remain part of our protocol for both macroscopic and
microscopic haematuria.
PMID- 17034504
TI - An immunohistochemical study of chromogranin A and human epidermal growth factor
2 expression using initial prostate biopsy specimens from patients with bone
metastatic prostate cancer.
AB - OBJECTIVES: To investigate, using prostate needle-biopsy specimens at diagnosis
from patients with bone metastatic prostate cancer, whether the relationship
between neuroendocrine (NE) cell differentiation and human epidermal growth
factor-2 (HER-2) expression is a prognostic factor for outcome. PATIENTS AND
METHODS: The study included 50 patients diagnosed as having bone metastatic
prostate cancer between January 1998 and December 2001. We tested for NE cell
differentiation by using immunohistochemical (IHC) staining for chromogranin A
(CgA), and for HER-2, using a commercial test for IHC staining. RESULTS: Eleven
patients (22%) were positive for CgA; there was a significant difference in the
time to recurrence (P = 0.025) but no significant differences in cause-specific
survival rate or survival rate after recurrence. In all, 21 patients (42%) were
positive for HER-2; the cause-specific survival rate, time to recurrence and
survival rate after recurrence were all significantly more favourable in the HER
2-negative group (P = 0.008, 0.049 and 0.025, respectively). In the 49 patients
for whom both factors could be determined, there was no significant correlation
between CgA and HER-2 positivity. CONCLUSIONS: NE cell differentiation of the
primary tumour in patients with bone metastatic prostate cancer does not reflect
the prognosis, whereas HER-2 overexpression is a prognostic factor for an
unfavourable outcome. These results suggest that NE cell differentiation is not
induced by HER-2.
PMID- 17034505
TI - Complications and neobladder function of the Hautmann orthotopic ileal
neobladder.
AB - OBJECTIVE: To report the complications and function of the Hautmann orthotopic
ileal neobladder . PATIENTS AND METHODS: In a 6.5-year period, 67 patients had an
ileal neobladder constructed after radical cystectomy as treatment for invasive
carcinoma of the bladder. All complications were reported systematically.
Neobladder function was assessed by patient interviews, uroflowmetry and
cystometric analyses. RESULTS: There were early complications in 41 patients
(61%), and late complications in 32 (48%); 23 (34%) had both early and late
complications and 17 (25%) had none. Eighteen of the patients (27%) required a re
operation for complications. At the 4-month follow-up, 90% were continent during
the day and 65% during the night; at 1 year after surgery 95% were continent
during the day and 73% during the night. The functional bladder capacity and
maximum cystometric capacity were close to the natural bladder volume (median 450
and 480 mL, respectively). CONCLUSIONS: Despite the high rate of complications in
this study, most were considered as minor and could be treated by conservative or
minimally invasive methods. The neobladder had an acceptable resemblance to the
native bladder in capacity and function. Consequently the ileal neobladder might
be preferred as a urinary diversion after radical cystectomy, if no
contraindications are present.
PMID- 17034506
TI - Surgical volume is related to the rate of positive surgical margins at radical
prostatectomy in European patients.
AB - OBJECTIVE: To assess the association between surgical volume (SV) and the rate of
positive surgical margins (PSM) after radical prostatectomy (RP) in a large
single-institution European cohort of patients. PATIENTS AND METHODS: In all,
2402 men had a RP by a group of 11 surgeons, all of whom were trained by the
surgeon with the highest SV; all surgeons used the same surgical technique.
Variables assessed before RP were prostate-specific antigen (PSA) level, clinical
stage and biopsy Gleason sum; variables assessed after RP were PSA level,
extracapsular extension, seminal vesicle invasion, lymph node invasion and
pathological Gleason sum. These were used to predict the rate of PSM in models
before or after RP. Multivariate models were complemented with SV to test its
independent and multivariate statistical significance and to quantify its impact
on the model's overall (and 200 bootstrap-corrected) predictive accuracy.
RESULTS: The mean (range) SV was 201 (1-1293) RPs; the mean (median, range) rate
of PSM was 20.2 (21.4, 0-32.9)%. In multivariate models, SV was a highly
statistically significant independent predictor of PSM (P < 0.001) and increased
the predictive accuracy in multivariate models both before (2.0%) and after RP
(1.5%, both P < 0.001). However, when the surgeon with the highest SV, who
contributed to 1293 cases, was removed from the analyses, the multivariate
independent prediction and the gains in predictive accuracy related to adding SV,
disappeared in the models both before (P = 0.9, accuracy gain 0.1%) and after (P
= 0.4, accuracy gain - 0.3%) RP. CONCLUSIONS: These results indicate that
patients treated by surgeons with a very high volume can expect to have a
significantly lower rate of PSM, after accounting for clinical and pathological
case-mix differences. However, SV is not a predictor of PSM when analyses are
restricted to intermediate- and low-volume surgeons.
PMID- 17034507
TI - Androgen receptor mutations are associated with Gleason score in localized
prostate cancer.
AB - OBJECTIVE: To study human androgen receptor (hAR) mutations and their
relationship to the clinical and pathological characteristics of patients with
prostate cancer, as the mechanisms by which tumour cells escape androgen control
and grow independently of hormone stimulation are unclear. PATIENTS AND METHODS:
In all, 67 radical prostatectomy specimens were sequenced genomically (mean age
of the patients, 64 years; median prostate-specific antigen level 15 ng/mL; 34%
T1 and 66% T2). Of the 66 patients who had a valid follow-up, 28 (43%) had
biochemical progression during the follow-up. RESULTS: There was mutation in the
hAR in 11 patients (16%); nine types of different mutations were identified, only
one of which was described previously in patients with prostate cancer. Patients
with mutated hAR had statistically lower Gleason scores (P = 0.004) than had
patients with native hAR. CONCLUSION: hAR mutations have a different effect on
the disease course in patients with localized than in those with metastatic
prostatic cancer.
PMID- 17034508
TI - Prognostic significance of common preoperative laboratory variables in clear cell
renal cell carcinoma.
AB - OBJECTIVE: To investigate the prognostic significance of common preoperative
laboratory variables evaluated before surgery for clear cell renal cell carcinoma
(RCC). PATIENTS AND METHODS: We retrospectively analysed the records of 355
patients who had surgery for clear cell RCC, assessing: clinical factors,
including preoperative laboratory measurements, i.e. haemoglobin level, leukocyte
count, platelet count, erythrocyte sedimentation rate (ESR), serum calcium,
alkaline phosphatase (ALP), albumin, bilirubin, alanine aminotransferase,
aspartate aminotransferase, and red blood cells in urine; and pathological
factors, with the survival rates after surgery. RESULTS: The presence of
metastasis, tumour stage and tumour size, with the ESR and ALP before surgery,
were identified as significant prognostic factors for progression-free survival
in a multivariate analysis. The same factors were significant independent factors
for disease-specific survival, except for ESR and ALP, which were nearly
statistically significant. When limited to non-metastatic tumours only, the
multivariate analysis showed that ESR and ALP, with tumour stage, grade, size and
necrosis, were independent prognostic factors for disease-specific survival.
CONCLUSIONS: Along with traditionally accepted prognostic factors, these results
suggest that common laboratory variables assessed before surgery, e.g. ESR and
ALP, might also be useful in assessing the prognosis for patients with non
metastatic clear cell RCC. Including various laboratory variables in prognostic
algorithms for RCC should be considered after further validation in RCCs of
various histological subtypes and stages.
PMID- 17034509
TI - Hot and cold technologies for tissue ablation in urology.
PMID- 17034510
TI - Is it possible to use urodynamic variables to predict upper urinary tract
dilatation in children with neurogenic bladder-sphincter dysfunction?
AB - OBJECTIVE: To investigate the possibility of using urodynamic variables to
predict upper urinary tract dilatation (UUTD) in children with neurogenic bladder
sphincter dysfunction (NBSD). PATIENTS AND METHODS: The study included 200
children with NBSD, of whom 103 had UUTD and 97 did not; they were examined using
routine urological, neurological and urodynamic methods. The group with UUTD was
divided into three subgroups (group 1-3, from mild to severe hydronephrosis). A
urodynamic risk score (URS) was calculated, including a detrusor leak-point
pressure (DLPP) of >40 cmH2O, a bladder compliance (BC) of <9 mL/cmH2O and
evidence of acontractile detrusor (ACD). RESULTS: The postvoid residual urine
volume (PVR), DLPP, incidences of ACD and DLPP of >40 cmH2O were greater and the
BC significantly less in groups 1-3 than in the control group. Moreover, the BC
decreased, while the PVR, DLPP and the incidence of DLPP of >40 cmH2O were
significantly higher in group 3 than in group 2. The relative safe cystometric
capacity of groups 2 and 3 were lower, respectively, than that of the control and
group 1, and the relative unsafe cystometric capacity (RUCC) and relative risk
rate of cystometric capacity (RRRCC) were significantly greater with the severity
of UUTD. The maximum detrusor pressure on voiding or at maximum flow rate, and
the Abrams-Griffiths number for voluntary contractile bladders, of the UUTD group
were significantly higher than those of the control group. There was a positive
correlation between URS and UUTD. CONCLUSIONS: The selective use of urodynamic
variables might be valuable for predicting the risk of UUTD in children with
NBSD. Decreased BC, and increased DLPP and ACD are the main urodynamic risk
factors, and they reciprocally increase the occurrence and grades of UUTD. The
grades of UUTD are compatible with increases in RUCC, RRRCC and URS.
PMID- 17034512
TI - Bleomycin and the skin.
AB - Bleomycin is frequently used as a chemotherapeutic agent to treat various kinds
of malignancy. However, the cytotoxic effects of bleomycin cause a number of
adverse responses, in particular in the lung and the skin. Bleomycin is used by
dermatologists as a treatment for various skin cancers, recalcitrant warts,
keloid and hypertrophic scars. This article discusses the use of bleomycin for
various skin disorders, as well as the risk factors and cutaneous side-effects
resulting from its use.
PMID- 17034513
TI - The role of neuropeptides in psoriasis.
AB - The pathogenesis of psoriasis is incompletely understood but cutaneous neurogenic
inflammation is probably involved. This involvement is suggested by a number of
clinical and histological observations. Reports about the distribution of
cutaneous nerves and the quantification of nerve growth factor and neuropeptides,
including calcitonin gene-related peptide and vasoactive intestinal peptide, in
lesional and nonlesional psoriatic skin suggest that sensory neuropeptides
contribute to the development of psoriasis. This review summarizes what is known
about the role of neurogenic markers in psoriasis.
PMID- 17034514
TI - Changes in the number of Merkel cells with the hair cycle in hair discs on rat
back skin.
AB - BACKGROUND: Hair discs are known to contain a large number of Merkel cells and
are ideal for investigating Merkel cell biology. Hair follicles, which are
important elements of hair discs, undergo unique cyclical morphological and
biological changes. OBJECTIVES: To define the relationships between the number
and the morphology of Merkel cells within the hair disc in association with the
hair cycle on rat back skin. METHODS: Merkel cells in hair discs were observed
three-dimensionally using immunohistochemistry. Epidermal sheets were incubated
with monoclonal murine antibody to CK20. As a result, Merkel cells in hair discs
were clearly demonstrated as whole shapes and were counted under a light
microscope. RESULTS: Merkel cells in hair discs increased during the early to
middle phase of anagen and decreased during the middle phase of anagen to catagen
and telogen in perinatal and postnatal rat back skin. We observed the
morphological variation of Merkel cells in hair discs of rat back skin, and
consequently divided them into two subtypes at the light microscopic level: the
oval type and the dendritic type. The number of oval-type Merkel cells was not
markedly affected by the hair cycle. In contrast, the number of dendritic-type
Merkel cells markedly changed with the hair cycle. CONCLUSIONS: This difference
of the hair cycle dependency between oval and dendritic-type Merkel cells
suggests some functional differences, such as a secretory function, related to
the hair cycle.
PMID- 17034515
TI - Sebum output as a factor contributing to the size of facial pores.
AB - BACKGROUND: Many endogenous and exogenous factors are known to cause enlarged
pilosebaceous pores. Such factors include sex, genetic predisposition, ageing,
chronic ultraviolet light exposure, comedogenic xenobiotics, acne and seborrhoea.
This study was an attempt to determine the factors related to enlarged pores.
OBJECTIVES: To assess the relationship of sebum output, age, sex, hormonal
factors and severity of acne with pore size. METHODS: A prospective, randomized,
controlled study was designed. A total of 60 volunteers, 30 males and 30 females,
were recruited for this study. Magnified images of pores were taken using a
dermoscopic video camera and measured using an image analysis program. The sebum
output level was measured with a Sebumeter. RESULTS: Using multiple linear
regression analysis, increased pore size was significantly associated with
increased sebum output level, sex and age. Among the variables, sebum output
level correlated most with the pore size followed by male sex. In comparing male
and female participants, males had higher correlation between the sebum output
level and the pore size (male: r = 0.47, female: r = 0.38). Thus, additional
factors seem to influence pore size in females. Pore size was significantly
increased during the ovulation phase (P = 0.008), but severity of acne was not
significantly associated with the pore size. CONCLUSIONS: Enlarged pore sizes are
associated with increased sebum output level, age and male sex. In female
patients, additional hormonal factors, such as those of the menstrual cycle,
affect the pore size.
PMID- 17034516
TI - Comedolytic effect of topically applied active vitamin D3 analogue on
pseudocomedones in the rhino mouse.
AB - BACKGROUND: Retinoids and active vitamin D(3) analogues regulate the
proliferation and differentiation of keratinocytes and are effective in the
treatment of psoriasis. Retinoids are known to be effective against acne vulgaris
through comedolysis. However, the comedolytic effect of active vitamin D(3)
analogues has not been reported. OBJECTIVES: To investigate whether maxacalcitol,
one of the active vitamin D(3) analogues, has a comedolytic effect by using
spontaneously comedogenic rhino mice. METHODS: Rhino mice were treated topically
with tretinoin and maxacalcitol once daily for 2 and 4 weeks, respectively. The
dermal side of the epidermal sheet was observed to determine the size of the
utricle. Haematoxylin and eosin-stained vertical sections were used to measure
utricle diameter and density and to evaluate histological changes. RESULTS:
Maxacalcitol (25 microg g(-1)) and tretinoin (0.1%) significantly decreased the
size and the diameter of the utricle after 1 week of treatment. However,
maxacalcitol did not affect the density while tretinoin did have an effect.
Histopathologically, maxacalcitol and tretinoin markedly induced epidermal
hyperplasia accompanied by a minor accumulation of inflammatory cells in the
dermis, with and without hypercornification, respectively. CONCLUSIONS: These
results indicate that maxacalcitol has a prominent effect on comedolysis and that
its mechanism of action may be different from that of retinoids.
PMID- 17034517
TI - Isolation and characterization of outer root sheath melanocytes of human hair
follicles.
AB - BACKGROUND: Outer root sheath melanocytes (ORSM) are not yet routinely cultured
and their biology is not known in detail because of their relatively low numbers
in the hair follicle and their limited proliferative capacity in in vitro culture
in routine media. OBJECTIVES: To develop a method for culturing ORSM more easily
and to investigate the length of telomeres and antigenic characteristics of ORSM
compared with epidermal melanocytes (EM). METHODS: Hair follicles were obtained
from three Korean individuals during hair transplantation surgery. Single-cell
suspensions of the outer root sheath were made and cultured in melanocyte growth
medium with stem cell factor. After 21 days, second-passage outer root sheath
keratinocytes (ORSK) (2 x 10(4) mL(-1) MGM) were added into the culture plates.
We studied the proliferation pattern, morphological and antigenic characteristics
of ORSM for each passage of cultured cells, and observed ORSM telomere length.
RESULTS: We established an ORSM culture method using ORSK. Two morphologically
different ORSM types were obtained in the primary cultures. At the end of primary
culture, ORSM appeared as whitish-cream pellets. The proliferation pattern of
ORSM showed a sigmoidal shape, the accumulated numbers of population doublings
showed a plateau after approximately 5 months, and senescence occurred at
approximately 33 +/- 5 accumulated population doublings. The length of ORSM
telomeres continued to shorten as the cells proliferated. In contrast, EM showed
a marked proliferation from the early proliferation period which formed a plateau
pattern towards the later period, and the number of accumulated population
doublings was estimated to be 18 +/- 5 after 2 months. ORSM in the primary
culture reacted variably with l-dihydroxyphenylalanine (DOPA): some cells were
DOPA negative, some DOPA positive. There were some different antigenic
expressions of microphthalmia-associated transcription factor (MITF) showing
cytoplasmic expression in ORSM and nuclear expression in EM. By nuclear
extraction and Western blotting, we showed that MITF expression of ORSM was
marked in the cytoplasm and minimal in the nucleus. Antigenic expression of MITF
and Bcl-2 gradually decreased with increasing passage number, whereas tyrosinase
related protein-1 expression did not change. CONCLUSIONS: Culture of ORSM
requires ORSK or ORSK-related factors; ORSM have greater proliferation potential
and show different MITF antigenic expression compared with EM; and the length of
ORSM telomeres shortens with repeated proliferation.
PMID- 17034518
TI - Investigation of the corticotropin-releasing hormone-proopiomelanocortin axis in
various skin tumours.
AB - BACKGROUND: Various types of external stress cause the skin and central
neuroendocrine system to express corticotropin-releasing hormone (CRH)
proopiomelanocortin (POMC) axis-related hormones. However, the precise role of
the CRH-POMC axis-related hormones in various skin tumours is unclear.
OBJECTIVES: This study examined expression patterns of the CRH-POMC axis-related
hormones in skin tumours. METHODS: The production of CRH, adrenocorticotropic
hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in various
tumour cell lines including HaCaT and primary keratinocytes was examined using an
enzyme-linked immunosorbent assay. Immunohistochemical analysis of the skin
tumours was also performed. RESULTS: CRH, ACTH and alpha-MSH were strongly
expressed in malignant skin tumour cell lines such as G-361 and DX-3 (both
malignant melanoma, MM). However, normal and haematological malignancy cell lines
did not express the CRH-POMC axis-related hormones. Immunohistochemical analysis
of the skin tumours showed that MM (80%), squamous cell carcinoma (SCC, 70%) and
basal cell carcinoma (BCC, 10%) had strong immunoreactivity (++/+++) for CRH.
Strong ACTH and alpha-MSH expression was observed in MM (70% and 50%,
respectively), SCC (80% and 60%, respectively) and BCC (70% and 50%,
respectively). CONCLUSIONS: We report that an increase in the level of the CRH
POMC axis-related hormones is associated with malignant skin tumours such as MM.
These results highlight the importance of the CRH-POMC axis-related hormones in
the malignant tendency of skin tumours.
PMID- 17034519
TI - Specialist dermatology clinics for organ transplant recipients significantly
improve compliance with photoprotection and levels of skin cancer awareness.
AB - BACKGROUND: Organ transplant recipients (OTRs) have 100-fold increased risk of
developing squamous cell carcinomas. Cumulative exposure to ultraviolet radiation
is the main risk factor and there is evidence that lack of dermatological
surveillance may be responsible for poor levels of knowledge and photoprotection
among OTRs. OBJECTIVES: This study evaluated whether routine consultation in a
specialist OTR dermatology clinic improves understanding of skin cancer risk and
compliance with photoprotection measures. METHODS: A cross-sectional
questionnaire-based study was performed in a specialist OTR dermatology clinic at
Bart's and the London NHS Trust, London, U.K. The subjects were 399 white-skinned
patients under surveillance in a renal transplant clinic, who were sent a postal
questionnaire from the renal transplant clinic. The main outcome measures were
responses to the questionnaire regarding photoprotective practices and skin
cancer risk awareness. RESULTS: Two hundred and ninety-two of 399 (73%)
responded, of whom 89% had previously attended the specialist dermatology clinic.
Ninety-six per cent recalled receiving photoprotection advice at least once (85%
from dermatologists); 92% reported use of sunscreen; 88% specifically dressed to
photoprotect themselves; 96% directly avoided sun exposure during summer; 68%
were aware that an increased risk of skin cancer was the reason that extra
photoprotective measures were important after a transplant. Photoprotective
measures and level of skin cancer awareness were significantly lower in those
responders who had never attended the specialist clinic. No obvious bias was
identified among nonresponders. CONCLUSIONS: Skin cancer awareness and compliance
with photoprotective measures in our patient population is generally greater than
previously reported, suggesting that delivery of educational messages regarding
skin cancer may be improved if provided in a specialist dermatological setting.
PMID- 17034520
TI - Follicular miniaturization in female pattern hair loss: clinicopathological
correlations.
AB - BACKGROUND: The pathology of female pattern hair loss (FPHL) is characterized by
an increase in the proportion of vellus follicles, manifest as a low
terminal/vellus ratio. This is conventionally thought to be due to a progressive
miniaturization of terminal hair follicles. There is also a prolongation of the
latent period of the hair cycle (kenogen) in both male pattern hair loss and FPHL
and follicles in kenogen may be difficult to classify histologically. Therefore,
a low terminal/vellus ratio could be due to a preferential increase in the number
of terminal follicles in kenogen rather than to a true increase in the number of
vellus follicles. OBJECTIVES: To establish whether there is an increase in the
absolute number of vellus follicles during the progression of FPHL, indicating a
process of follicular miniaturization. METHODS: We studied 42 women complaining
of hair loss. The severity of the hair loss was graded clinically on a five-point
scale from 1 (no obvious hair loss) to 5 (severe hair loss). Three 4-mm punch
biopsies were taken from the frontal scalp of each patient, sectioned
horizontally and stained with haematoxylin and eosin. Two levels were studied on
each biopsy: through the mid-infundibular region and through the mid-isthmus. The
following were counted: total follicles, terminal follicles, vellus follicles,
anagen and telogen/catagen follicles. The results from the three biopsies from
each subject were averaged and statistical evaluations performed on the mean
values. RESULTS: There was a progressive decline in mean total follicle count
with increasing grade of hair loss (grade 1, 317 cm(-2); grade 5, 243 cm(-2)) and
a more pronounced reduction in terminal follicle counts (grade 1, 263 cm(-2);
grade 5, 96 cm(-2)). The absolute number of vellus follicles increased from 33
cm(-2) (grade 1) to 71 cm(-2) (grade 4), declining to 51 cm(-2) at grade 5. The
terminal/vellus ratio fell from 12.8 (grade 1) to 2.3 (grade 4) and remained at
this level thereafter. The proportion of follicles in telogen increased from
13.7% (grade 1) to 31.4% (grade 5). CONCLUSIONS: Our results show that there is
an increase in vellus follicle numbers with increasing severity of hair loss in
women with FPHL, suggesting that terminal follicles do indeed miniaturize. It is
possible that there is also an increase in the number of follicles in a latent
stage of telogen but this was difficult to assess from our data. The fall in
total follicle counts with stabilizing of the terminal/vellus ratio in severe
hair loss suggests that miniaturization does not stop with a vellus follicle but
progresses to follicular deletion.
PMID- 17034521
TI - Cytokine alterations in lichen sclerosus: an immunohistochemical study.
AB - BACKGROUND: Although the histology of lichen sclerosus is characteristic, the
precise nature of the inflammatory changes and the signals provoking them is
uncertain. OBJECTIVES: To delineate the inflammatory changes in lichen sclerosus
more accurately by studying cytokine changes. METHODS: An immunohistochemical
study of 12 specimens of genital lichen sclerosus and one specimen of
extragenital lichen sclerosus was undertaken using monoclonal antibodies to
interferon (IFN)-gamma, IFN-gamma receptor, tumour necrosis factor (TNF)-alpha,
interleukin (IL)-1alpha, IL-2 receptor (CD25), intercellular adhesion molecule-1
(ICAM-1) and its ligand CD11a. Control specimens were seven specimens of normal
vulva obtained during gynaecological procedures, three specimens of normal skin,
adjacent uninvolved thigh from three of the patients with lichen sclerosus, five
specimens of nonvulval psoriasis, four specimens of nonvulval lichen planus and
two specimens from chronic wounds. RESULTS: The lichen sclerosus specimens
demonstrated slightly increased staining for IFN-gamma within the epidermis
compared with the normal vulva and nonvulval skin. There was increased dermal
staining for IFN-gamma both within the pale zone of the upper dermis and within
the inflammatory zone below this. We confirmed our previous demonstration that in
lichen sclerosus HLA-DR immunostaining is increased in association with vascular
endothelium, the inflammatory cell infiltrate and around the keratinocytes. The
areas of the epidermis with the strongest immunostaining for HLA-DR generally
also had the strongest staining for IFN-gamma. In the lichen sclerosus specimens
the zone of inflammation also demonstrated increased immunostaining for TNF
alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 while the zone of
sclerosus demonstrated a smaller increase in immunostaining for IFN-gamma
receptor, TNF-alpha, CD11a and ICAM-1, and the epidermis demonstrated increased
staining for ICAM-1. CONCLUSIONS: The increased staining for IFN-gamma, TNF
alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 suggest that the
cytokine response in lichen sclerosus shares characteristics of the cytokine
response in lichen planus and chronic wounds.
PMID- 17034522
TI - Prospective aetiological study of diaper dermatitis in the elderly.
AB - BACKGROUND: The different causes of diaper dermatitis (DD) in the elderly are not
well known and the treatment is often empirical. OBJECTIVES: To determine the
causes of DD in the elderly and to evaluate the efficacy of antifungal treatments
in this indication. METHODS: Consecutive patients presenting with DD were
included. Clinical evaluation, skin swabs for bacterial and mycological cultures,
patch testing and skin biopsy were performed at inclusion. This was followed by 1
month of topical antifungal cream and, if needed, by oral fluconazole for the
second month. RESULTS: Forty-six patients were included (mean age 85 years).
Causes of DD were established for 38 patients: 24 had candidiasis (63%), six
irritant dermatitis (16%), four eczema (11%) and four psoriasis (11%). After 2
months of treatment, 27 of 37 (73%) patients were cured and five of 37 were
improved. CONCLUSIONS: Mycoses and irritant dermatitis are the main causes of DD
in the elderly, and emollient skin care and topical antifungal treatment can be
considered a first-line therapy for this indication.
PMID- 17034523
TI - Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the
lower leg: a series with community follow-up.
AB - BACKGROUND: Cellulitis of the lower leg is a common problem with considerable
morbidity. Risk factors are well identified but the relationship between
consequences of cellulitis and further episodes is less well understood.
OBJECTIVES: To review risk factors, treatment and complications in patients with
lower leg cellulitis, to determine the frequency of long-term complications and
of further episodes, and any relationship between them, and to consider the
likely impact of preventive strategies based on these results. METHODS: Patients
with ascending, presumed streptococcal, cellulitis of the lower leg were
identified retrospectively from hospital coding. Hospital records, together with
questionnaires to both general practitioners and patients, were used to record
subsequent complications and identifiable risk factors for further episodes.
RESULTS: Of 171 patients, 81 (47%) had recurrent episodes and 79 (46%) had
chronic oedema. The concurrence of these two factors was strongly correlated (P <
0.0002). Based on 143 completed questionnaires, oedema was apparently due to or
persistently asymmetrical after the cellulitic episode in 52 (37%), and 19 (13%)
had ulceration attributed to, rather than causing, cellulitis. Of those with
three or more episodes, half did not lead to hospital admission. Toeweb
maceration was reported in only 15% of questionnaires. Use of antibiotic
treatment for more than 28 days was associated with a reduced risk of leg
ulceration or of prolonged oedema compared with shorter courses, but neither
difference was statistically significant. CONCLUSIONS: This study demonstrates
that the true frequency of postcellulitic oedema, as well as that of further
episodes, is probably underestimated. Furthermore, there is a strong association
between these factors, each of which is both a risk factor for, and a consequence
of, each other, and for which intervention (reduction of oedema or more prolonged
antibiotic therapy) may reduce the risk of recurrent infection. By contrast, self
reporting of toeweb maceration is low, so attempts to reduce the risk of
recurrent cellulitis by treatment of tinea pedis or bacterial intertrigo may
fail.
PMID- 17034524
TI - Dermoscopy of facial nonpigmented actinic keratosis.
AB - BACKGROUND: The accuracy of clinical diagnosis of nonpigmented, facial actinic
keratosis (AK) is often suboptimal, even for experienced clinicians. OBJECTIVES:
To investigate the dermoscopic features of nonpigmented AK located on the
head/neck that may assist the clinical diagnosis. METHODS: Forty-one nonpigmented
AKs on facial sites were examined by dermoscopy for any consistent underlying
features. Lesions were gathered from skin cancer centres in Australia, Austria,
Italy and the U.S.A. All cases were diagnosed histopathologically. RESULTS: Four
essential dermoscopic features were observed in facial AK: (i) erythema,
revealing a marked pink-to-red 'pseudonetwork' surrounding the hair follicles
(95%); (ii) white-to-yellow surface scale (85%); (iii) fine, linear-wavy vessels
surrounding the hair follicles (81%); and (vi) hair follicle openings filled with
yellowish keratotic plugs (66%) and/or surrounded by a white halo (100%). These
features combined, in 95% of cases, to produce a peculiar 'strawberry'
appearance. CONCLUSIONS: A dermoscopic model of 'strawberry' pattern is
presented, which may prove helpful in the in vivo diagnosis of nonpigmented,
facial AK. A limitation of this study is the lack of testing of the specificity
of the described dermoscopic criteria in differentiating nonpigmented AKs from
other nonpigmented skin lesions at this site.
PMID- 17034525
TI - Pruritus as a leading symptom: clinical characteristics and quality of life in
German and Ugandan patients.
AB - BACKGROUND: Pruritus is the most frequent and distressing symptom associated with
dermatoses and various internal and neurological diseases. OBJECTIVES: To
investigate two different populations of patients with pruritus, one in Germany
and one in Uganda, with a particular focus on clinical characteristics, aetiology
and quality of life. METHODS: We investigated by questionnaire 132 patients (59
men, 73 women, mean age 54.5 years) who were referred to the Department of
Dermatology at the University Hospital of Magdeburg, Germany, with the diagnosis
of pruritus as a leading symptom. The questionnaire was also applied in 84
patients who consulted the Dermatology Clinic at Mbarara, Uganda for pruritus.
The questions referred to personal data and disease history of the individual,
history and present occurrence of concomitant diseases, present and past therapy,
quality, frequency and triggers of itching and scratching, other disorders and
complaints, quality of life and impact on work and disability. RESULTS: Seventy
five (57%) of the German patients had pruritus due to dermatoses, 47 patients
(36%) had pruritus due to a systemic disease and in 10 patients (8%) pruritus was
of unknown origin. Most had a history of pruritus of several months up to years.
Pruritus associated with dermatoses mostly affected the whole body and was
permanent with an undulatory character. Affective reactions such as aggression
and depression occurred more frequently in dermatological patients compared with
those with systemic pruritus. The former group felt that pruritus had a greater
impact on their lives. Almost all Ugandan patients had pruritus due to dermatoses
except for three patients with pruritus of unknown origin. Eczema and prurigo
were the most frequently observed dermatoses in both German and Ugandan patients.
Patients with pruritus in both populations showed an impaired quality of life.
There was no pronounced difference between the populations with regard to
feelings of depression and suicidal thoughts. CONCLUSIONS: A great deal of
helpful information in this complex group of patients can be obtained using this
questionnaire. Pruritus has a major impact on quality of life and especially
impairs those patients with pruritus associated with dermatoses and pruritus of
unknown origin.
PMID- 17034526
TI - Striae gravidarum in primiparae.
AB - BACKGROUND: Striae distensae are widely known to occur in pregnancy and
aesthetically they can be a cause of great concern for many women. Various
factors have been reported to be associated with the development of striae but
the results are conflicting. OBJECTIVES: To observe the prevalence of striae
gravidarum in primiparae and identify independent associated risk factors.
METHODS: An observational analysis of 324 primiparae was conducted within 48 h of
delivery. Data was collected in the form of a questionnaire and physical
examination. Seventy-two primiparae participated in a pilot study in 1999 and the
remaining were assessed over a 4-month period in 2000. Seventeen variables were
recorded, and striae graded according to quantity and severity. Fifteen
primiparae were excluded prior to analysis. RESULTS: Fifty-two per cent (161 of
309) of primiparous white women had striae of which 12% (20 of 161) were
classified as severe. The most significant risk factor was low maternal age (P <
0.0001). Twenty per cent (14 of 71) of teenagers had severe striae, a finding not
seen in women over 30 years of age. Other significant risk factors included
maternal body mass index greater than 26 (P = 0.0003), maternal weight gain of
more than 15 kg (P = 0.0121) and high neonatal birth weight (P = 0.0135).
CONCLUSIONS: Logistic regression analysis demonstrated that maternal age, body
mass index, weight gain and neonatal birth weight were independently associated
with the occurrence of striae. It appears that the group at highest risk of
developing severe striae are teenagers. This finding is important and may provide
impetus to explore the pathomechanisms of striae.
PMID- 17034527
TI - Cutaneous innervation before and after one treatment period of acupuncture.
AB - BACKGROUND: The effect of acupuncture on nociceptive pain is well documented, but
effects on nociceptive itch have been contradictory. OBJECTIVES: To evaluate
possible effects of acupuncture on the occurrence, distribution and function of
sensory nerve fibres in human skin. METHODS: Ten subjects were treated by
inserting 10 acupuncture needles subcutaneously at the upper lateral aspect of
one buttock. The subjects were recruited from an acupuncture clinic and were
undergoing specific acupuncture treatment for their disorders. The needles were
stimulated (rotated to and fro) twice during the twice-weekly 25-min sessions
over 5 weeks. Skin biopsies, diameter 3 mm, were taken before and 3-6 days after
local acupuncture. Antibodies to the pan-neuronal marker protein gene product 9.5
(PGP 9.5), calcitonin gene-related peptide (CGRP), vanilloid receptor 1 (VR1) and
mu- and delta-opioid receptors were employed to study sensory unmyelinated nerve
fibres that transmit nociceptive pain and itch. A histamine prick test using
planimetry was used to record experimental itch after acupuncture on the treated
area and on the corresponding control skin, and a visual analogue scale was used
to evaluate itch. RESULTS: The mean +/- SEM number of CGRP-immunoreactive nerve
fibres per biopsy section was reduced from 36.0 +/- 3.3 to 21.3 +/- 4.0 (P =
0.05) after the treatment. PGP 9.5-immunoreactive nerve fibres were found both in
the epidermis and in the subpapillary dermis. The mean +/- SEM total number of
PGP 9.5-immunoreactive nerve fibres decreased from 249.8 +/- 16.7 to 211.8 +/-
12.0 (P = 0.03). The PGP 9.5-immunoreactive nerve fibres occurring in the dermis
appeared more fragmented after the acupuncture compared with pretreatment. VR1
immunoreactivity was found both in the free nerve fibres and in kite-like
formations, possibly mast cells, throughout the dermis, sometimes occurring
around hair follicles. The mean +/- SEM number of VR1-immunoreactive elements was
not significantly influenced by acupuncture, at 33.5 +/- 4.6 vs. 43.0 +/- 4.4 (P
= 0.09). No immunoreactivity was found in the skin against mu- and delta-opioid
receptors with the antibodies used in this study. Neither histamine-induced itch
nor cutaneous responses were influenced by acupuncture. CONCLUSIONS: The present
data indicate an effect of acupuncture on neuropathic itch but not histamine
mediated itch. Our findings support the opinion that the pain-relieving effects
of acupuncture partly depend on its effect on the peripheral innervation.
PMID- 17034528
TI - Characteristics of cutaneous cytomegalovirus infection in non-acquired immune
deficiency syndrome, immunocompromised patients.
AB - BACKGROUND: Although cytomegalovirus (CMV) disease is a severe complication among
immunocompromised patients, its cutaneous features have not been frequently
reported. As herpes simple virus (HSV) infection commonly develops in CMV skin
lesions, a study is needed on the pathogenetic role of CMV in cutaneous lesion
formation. OBJECTIVES: The purpose of this study is to characterize the clinical
and histopathological features of cutaneous CMV infection and to determine
whether CMV plays a true pathogenetic role in cutaneous lesions, or if it is just
an innocent bystander during HSV infection among non-AIDS (acquired immune
deficiency syndrome), immunocompromised patients. PATIENTS AND METHODS: A total
of nine human immunodeficiency virus-negative patients diagnosed with cutaneous
CMV infection from July 1999 to February 2005 at Samsung Medical Center were
analysed in terms of their clinical and histopathological characteristics. In
addition, we examined for the co-presence of HSV by performing
immunohistochemical analysis and polymerase chain reaction. RESULTS: All the
patients were immunocompromised; five had haematological diseases and four were
organ transplant recipients. The clinical and histopathological features were
similar to those of previous studies of patients with AIDS. Multiple anogenital
ulcerations were the most frequent cutaneous presentation (66.7%). Most
cytopathic changes were found in the dermis, particularly within the vascular
endothelial cells (77.8%) and macrophages (66.7%). However, the association of
CMV with concurrent HSV infection was even lower than that seen in patients with
AIDS. Only one patient revealed a co-existing cutaneous HSV infection.
CONCLUSIONS: In non-AIDS individuals, the cutaneous lesions from CMV infection
showed similar clinical and histopathological features to those of patients with
AIDS. However, skin lesions may not be highly associated with HSV, and CMV does
seem to contribute to lesion development as a cutaneous manifestation among the
CMV infected, non-AIDS, immunocompromised patients.
PMID- 17034529
TI - Elevated serum IgA anticardiolipin antibody levels in adult Henoch-Schonlein
purpura.
AB - BACKGROUND: Henoch-Schonlein purpura (HSP) is a small-vessel vasculitis
characterized by palpable purpura on the lower extremities and IgA-dominant
immune complex deposition within the wall and lumen of dermal vessels in the
lesions. This disorder is associated, to varying degrees, with joint,
gastrointestinal and renal involvement. Antiphospholipid antibodies, including
anticardiolipin antibodies (aCL Abs), are a heterogeneous group of circulating
autoantibodies found in patients with autoimmune and infectious diseases.
OBJECTIVES: To investigate the possible role of aCL Abs in adult HSP, we measured
levels of serum IgA, C-reactive protein (CRP), aCL Abs of the IgG, IgM and IgA
isotypes and anti-beta(2)-glycoprotein I (beta(2)GPI)-dependent aCL Abs in adult
patients with HSP. We evaluated the correlation between these biological
parameters and the clinical manifestations. METHODS: Adult patients with HSP with
an initial cutaneous manifestation of palpable purpura on their lower extremities
seen between 2001 and 2005 in our department were retrospectively reviewed.
Patients with known connective tissue diseases were not included in the study.
Histological examination of all patient skin biopsy specimens revealed
leucocytoclastic vasculitis in the upper and mid-dermis. Direct
immunofluorescence analysis showed prominent deposits of IgA in the capillary
walls of all patients. Blood samples were taken at the time that the patient
presented. Serum levels of aCL Abs and anti-beta(2)GPI-dependent aCL Abs were
measured by enzyme-linked immunosorbent assay. RESULTS: Twenty adult patients
with HSP (12 men and eight women), mean age 62.2 years (range 23-81) were
enrolled. IgA aCL Abs were found in 15 of the 20 patients (75%). All were
negative for IgG aCL Abs, IgM aCL Abs and anti-beta(2)GPI-dependent aCL Abs. The
elevation of serum IgA aCL Abs in the 15 patients showed a significant
correlation with serum IgA and CRP levels (r(s) = 0.91, P = 0.0007; r(s) = 0.80,
P = 0.0026, respectively). Levels of serum IgA aCL Abs were also significantly
associated with arthralgia (P = 0.022) and proteinuria according to urinalysis (P
= 0.013). CONCLUSIONS: Serum levels of IgA aCL Abs are elevated in the initial
active stage of adult HSP, suggesting that serum IgA aCL Abs may play some role
in the onset of adult HSP. We believe that serum IgA aCL Abs might be an
indicator of adult HSP activity.
PMID- 17034530
TI - Dysplastic naevi with moderate to severe histological dysplasia: a risk factor
for melanoma.
AB - BACKGROUND: The risk of malignant melanoma associated with histologically
dysplastic naevi (HDN) has not been defined. While clinically atypical naevi
appear to confer an independent risk of melanoma, no study has evaluated the
extent to which HDN are predictive of melanoma. OBJECTIVES: To estimate the risk
of melanoma associated with HDN. Secondarily, the risk associated with number of
naevi and large naevi is estimated. METHODS: We enrolled 80 patients with newly
diagnosed melanoma along with 80 spousal controls. After obtaining information on
melanoma risk factors and performing a complete cutaneous examination, the most
clinically atypical naevus was biopsied in both cases and controls. Histological
dysplasia was then assessed independently by 13 dermatopathologists (0, no
dysplasia; 1, mild dysplasia; 2, moderate dysplasia; 3, severe dysplasia). The
dermatopathologists were blinded as to whether the naevi were from melanoma
subjects or controls. Multivariate analyses were performed to determine if there
was an independent association between the degree of histological dysplasia in
naevi and a personal history of melanoma. RESULTS: In persons with naevi
receiving an average score of > 1 (i.e. naevi considered to have greater than
mild histological dysplasia), there was an increased risk of melanoma [odds ratio
(OR) 2.60, 95% confidence interval (CI) 0.99-6.86] which persisted after
adjustment for confounders (OR 3.99, 95% CI 1.02-15.71). Very few
dermatopathologists reliably graded naevi of subjects with melanoma as being more
dysplastic than naevi of control subjects. Among the entire group, the
interobserver reliability associated with grading histological dysplasia in naevi
was poor (weighted kappa 0.28). CONCLUSIONS: HDN do appear to confer an
independent risk of melanoma. However, this result may add more to our biological
understanding of melanoma risk than to clinical assessment of risk, because HDN
assessed by a single pathologist generally cannot be used to assess risk of
melanoma. Future studies should be directed at establishing reproducible,
predictive criteria for grading naevi.
PMID- 17034531
TI - Prevalence of vulval lichen planus in a cohort of women with oral lichen planus:
an interdisciplinary study.
AB - BACKGROUND: Lichen planus (LP) is a mucocutaneous inflammatory dermatosis that
frequently involves the oral and genital mucosae. Patients with LP affecting
these sites are often seen by oral medicine specialists or gynaecologists who
work in isolation and depend heavily on histopathologists to help them in
confirming the diagnosis. There are few studies in the literature combining the
experiences of these specialists who share the care of patients with both oral
and genital LP. OBJECTIVES: To estimate the prevalence of vulval LP (VLP) in a
cohort of patients with histologically confirmed oral LP (OLP). METHODS: The
study group consisted of 42 women histologically diagnosed with OLP. The mean age
was 60.5 years (range 27-81). They underwent genital examination, colposcopy and
vulvoscopy. For the histological confirmation of clinical VLP biopsies were
performed whenever a clinical lesion was found. Oral and genital biopsy specimens
were processed through histological and immunohistochemical staining.
Histological diagnoses of LP were made according to the modified World Health
Organization histopathological criteria proposed by van der Meij and van der Waal
for the diagnosis of OLP, and extended to VLP. Patients with clinical evidence,
but without the histological confirmation of OLP and VLP, were excluded from the
study group. RESULTS: Thirty-two vulval and one vaginal biopsy specimens were
obtained. Histological diagnoses were confirmed in 24 of 32 (75%) patients who
underwent a vulval biopsy: these represent 57% (24 of 42) of the study group. Of
the 12 patients free of symptoms such as itching, burning and dyspareunia, but
with clinical vulval lesions, 11 (92%) had histological confirmation of VLP.
Vulval lichen sclerosus was ascertained in five of 32 (16%) cases. CONCLUSIONS:
This study showed a 57% prevalence of VLP in selected patients with OLP. The high
prevalence of VLP of 92% in the women who were free of vulval symptoms confirmed
the usefulness of this careful integrated approach.
PMID- 17034532
TI - Epigenetic abnormalities in cutaneous squamous cell carcinomas: frequent
inactivation of the RB1/p16 and p53 pathways.
AB - BACKGROUND: Aberrant methylation of CpG islands in the promoter regions of cancer
related genes has been demonstrated in many human tumours. However, the
methylation profile of these regions in cutaneous squamous cell carcinomas (SCCs)
has not been well studied. OBJECTIVES: To examine epigenetic abnormalities of a
wide range of cancer-related genes in SCCs. METHODS: We investigated the
methylation status of 11 candidate cancer-related genes (CDH1, p16(INK4a),
p14(ARF), DAPK1, MGMT, RB1, RASSF1, p15(INK4b), PTEN, PRDM2 and p53) in 20 cases
of SCC by methylation-specific polymerase chain reaction, and comparatively
examined the protein production of E-cadherin (CDH1), p16, RB1, p14, BMI1 and
cyclin A by immunohistochemical analysis. RESULTS: The frequency of cancer
related gene methylation in SCCs was: CDH1 (95%), p16 (20%), p14 (15%), DAPK1
(15%), MGMT (15%), RB1 (5%), RASSF1 (5%), p15 (0%), PTEN (0%), PRDM2 (0%) and p53
(0%). Almost all cases with hypermethylation of CDH1, p16, RB1 and p14 showed no
obvious production of each protein, suggesting that promoter hypermethylation of
these genes contributes to the loss of protein production. The results of
methylation analysis, in combination with the results of our previous mutation
analysis of CDKN2A locus and p53, revealed that 70% of SCCs have alterations in
the RB1/p16 or p53 pathway. CONCLUSIONS: Our findings indicate that the promoter
hypermethylation of cancer-related genes, especially CDH1, is frequently shown in
SCCs, and dysregulation of the RB1/p16 and/or p53 pathway through either genetic
or epigenetic mechanisms, except for epigenetic abnormalities of p53 itself,
should contribute to the carcinogenesis of SCCs.
PMID- 17034533
TI - Poor agreement between self-reported and dermatologists' diagnoses for five
common dermatoses.
AB - BACKGROUND: Few epidemiological studies assessing the prevalence of chronic
dermatosis are available in France and most of these studies have used biased
samples drawn from specific subpopulations. As several recent studies have
mentioned that self-reported diagnosis either underestimates or overestimates
disease prevalence, the validity of such data is questionable. OBJECTIVES: To
evaluate the agreement between self-reported and dermatologists' diagnoses for
five chronic dermatoses: acne, eczema, fungal infection, psoriasis and
seborrhoeic dermatitis, and to analyse the factors associated with patients'
diagnosis knowledge. PATIENTS/METHODS: A cross-sectional study was conducted on
the national day of skin tumour screening in April 2003. A self-administered
questionnaire was completed by patients and a standard form was completed by
dermatologists after clinical examination. A total of 4,622 adults were examined
by a dermatologist in 134 screening centres across France. The agreement between
self-reported and dermatologists' diagnoses was analysed using the kappa index.
Characteristics of patients who were aware of their diagnosis were compared with
those of patients who were not, by using multivariate logistic regression models.
RESULTS: The demographic characteristics of the sample differed from those of the
French population. The self-reported prevalence was significantly lower than the
actual prevalence for all diseases except eczema. Underestimations ranging from
23% to 35% were observed in nearly all subgroups of our population. The agreement
between self-reported and dermatologists' diagnoses was low to moderate. Many
cases of chronic skin diseases were diagnosed in patients who did not report
them. Diagnosis knowledge was poorer in those above 54 years of age and better
for patients treated for the condition and those with impairment of social life.
CONCLUSIONS: We observed a low agreement between self-reported and
dermatologists' diagnoses for five chronic diseases. Self-reports underestimated
the actual prevalence of four of five common diseases.
PMID- 17034534
TI - Evaluation of methotrexate and corticosteroids for the treatment of localized
scleroderma (morphoea) in children.
AB - BACKGROUND: Localized scleroderma (LS) or morphoea is often considered to be a
benign self-limiting condition confined to the skin and subcutaneous tissue.
However, the course of the disease is unpredictable and severe functional and
cosmetic disability may result. Drug treatment with systemic corticosteroids in
combination with methotrexate has been reported to be beneficial in LS, but data
in children is limited. OBJECTIVES: To evaluate the efficacy and tolerability of
systemic corticosteroids in combination with methotrexate in children with LS.
METHODS: Treatment and outcome of 34 patients with LS were retrospectively
analysed. Pulsed intravenous methylprednisolone was given, followed by oral
prednisolone on a reducing regimen and maintenance treatment with methotrexate.
We assessed treatment outcome clinically and by thermography and monitored
adverse events. RESULTS: From the onset of treatment, the disease stopped
progressing in 94% of the patients. All patients demonstrated significant
clinical improvement within a mean time of 5.7 +/- 3.9 months. Mean duration of
follow-up over the treatment period and beyond was 2.9 +/- 2.0 years. In 16 (47%)
patients therapy was discontinued when the disease was considered to be inactive
clinically; however, seven (44%) of the 16 developed a relapse, necessitating
repeat treatment. At last follow-up (range 0.2-7.0 years), 24 (71%) of the 34
patients had completely inactive disease. Observed adverse events were moderate
and transient and no patient had to stop therapy. CONCLUSIONS: These data suggest
that systemic corticosteroids and methotrexate in combination are beneficial and
well tolerated in the treatment of children with LS. Because of the risk of
relapse after discontinuing therapy, long-term monitoring is mandatory.
PMID- 17034535
TI - Multicentre, phase II trial on the safety and efficacy of topical tacrolimus
ointment for the treatment of lichen sclerosus.
AB - BACKGROUND: Lichen sclerosus is a chronic inflammatory autoimmune disease causing
significant sclerosis, atrophy and pruritus. Treatment remains unsatisfactory,
with potent corticosteroids being the most effective therapy. OBJECTIVES: To
conduct a multicentre, phase II trial to assess the safety and efficacy of
tacrolimus ointment 0.1% for the treatment of lichen sclerosus with a follow-up
period of 18 months at 10 university and teaching hospitals in Germany and
Austria. METHODS: Eighty-four patients (49 women, 32 men and three girls) aged
between 5 and 85 years with long-standing, active lichen sclerosus (79 with
anogenital and five with extragenital localization) were treated with topical
tacrolimus ointment 0.1% twice daily for 16 weeks. Computerized analysis of the
lesional area was performed. The primary endpoint was clearance of active lichen
sclerosus. Secondary endpoints were time to optimal response, reduction of
sclerosis and duration of remission. RESULTS: The primary endpoint (clearance of
active lichen sclerosus) was reached by 43% of patients at 24 weeks of treatment.
Partial resolution was reached in 34% of patients. Maximal effects occurred
between week 10 and 24 of therapy. Treatment led to a significant reduction of
the total lesional area (P < 0.01) and to a significant decline in the total
symptom score (P < 0.005). Symptoms (e.g. itching) and findings (erythema,
erosions and induration) showed significant improvement. No serious adverse
events were observed. There were three (9%) recurrences during the follow-up
period. CONCLUSIONS: Topical tacrolimus ointment 0.1% was safe and effective for
the treatment of long-standing active lichen sclerosus.
PMID- 17034536
TI - Intraindividual, right-left comparison of topical methyl aminolaevulinate
photodynamic therapy and cryotherapy in subjects with actinic keratoses: a
multicentre, randomized controlled study.
AB - BACKGROUND: Actinic keratosis (AK), the most common premalignant skin condition,
can represent a management challenge. Treatment should not only be effective, but
also well tolerated and allow for good cosmesis on typical sun-exposed highly
visible body sites. OBJECTIVES: The primary objective was to compare the lesion
response and subject preference for topical methyl aminolaevulinate (MAL)
photodynamic therapy (PDT) vs. cryotherapy for the treatment of AK. METHODS: In
this 24-week, multicentre, randomized, intraindividual (right-left) study,
subjects received both one treatment session of MAL-PDT and a double freeze-thaw
cryotherapy; the treatments were randomly allocated to either side of the
face/scalp. Lesions with a noncomplete response were retreated after 12 weeks.
The primary assessments were the subject's overall preference and lesion response
at week 24. Secondary assessments included lesion response at week 12, cosmetic
outcome, subject and investigator cosmetic outcome preference at week 24, and
investigator overall preference at week 24. Skin discomfort and adverse events
were also evaluated. RESULTS: In total, 119 subjects with 1,501 lesions were
included in the study. At week 12, treatment with MAL-PDT resulted in a
significantly larger rate of cured lesions relative to cryotherapy (percentage
lesion reduction from baseline: 86.9% vs. 76.2%; P < 0.001). At week 24, both
treatment groups showed a high rate of cured lesions (89.1% for MAL-PDT vs. 86.1%
for cryotherapy; P = 0.20; 95% confidence interval: -1.62 to 7.67). Results for
subject and investigator preferences as well as cosmetic outcome favoured MAL
PDT. Both treatment regimens were safe and well tolerated. CONCLUSIONS: The
present study shows that, when treated with both MAL-PDT and cryotherapy,
subjects significantly prefer MAL-PDT treatment for AK. MAL-PDT is an attractive
treatment option for AK, with comparable efficacy and superior cosmetic outcomes
compared with double freeze-thaw cryotherapy.
PMID- 17034537
TI - FK506 increases pigmentation and migration of human melanocytes.
AB - BACKGROUND: Topical tacrolimus (FK506) is a potential therapeutic option for
vitiligo management. Despite its clinical efficacy, the underlying mechanism of
how topical tacrolimus induces repigmentation in vitiligo has scarcely been
investigated. OBJECTIVES: To investigate the direct effects of FK506 on
pigmentation and migration of human melanocytes. METHODS: Cell proliferation was
measured using a Coulter counter. The effects on pigmentation were investigated
by measuring melanin contents, tyrosinase activity and tyrosinase expression. To
determine the effects of FK506 on cell migration, we performed scratch assays and
Boyden chamber assays. RESULTS: FK506 treatment increased melanin contents,
although there was an inhibitory effect on growth of melanocytes. The increase of
pigmentation was due to the result of the stimulatory action of FK506 on
tyrosinase activity and its expression, which eventually led to melanin
biosynthesis. Furthermore, cell migration was enhanced by FK506 treatment.
CONCLUSIONS: These findings provide in vitro evidence demonstrating direct
effects of FK506 on pigmentation and melanocyte migration and may provide a
possible mechanism for the effect of tacrolimus in vitiligo.
PMID- 17034538
TI - Absent/reduced glucose transporter-1 protein expression in infantile subglottic
haemangiomas.
AB - BACKGROUND: Positive immunohistochemical staining for glucose transporter-1
protein (GLUT1) is a characteristic of cutaneous infantile haemangiomas.
OBJECTIVES: To examine GLUT1 expression in subglottic haemangiomas. METHODS:
Review of clinical notes and biopsy tissue with immunostaining for GLUT1 in 14
patients with subglottic haemangiomas. RESULTS: GLUT1 immunostaining was negative
in 11 cases, and focally positive in three. No subglottic haemangiomas
demonstrated the intense diffuse positive GLUT1 staining seen in cutaneous
infantile haemangiomas. Five patients had cutaneous as well as subglottic
haemangiomas, one of whom had a GLUT1-negative subglottic haemangioma and a GLUT1
positive cutaneous haemangioma of the lip. CONCLUSIONS: Subglottic haemangiomas
appear immunohistochemically different from cutaneous infantile haemangiomas,
which may reflect differences in endothelial cell differentiation or underlying
aetiology.
PMID- 17034539
TI - Efalizumab-induced autoimmune pancytopenia.
AB - Efalizumab is a recombinant, humanized monoclonal anti-CD11a antibody used for
the treatment of moderate to severe plaque psoriasis. Immune-mediated
thrombocytopenia and anaemia have previously been reported with this therapy. We
describe the first case of immune-mediated pancytopenia in a patient treated with
efalizumab. Close monitoring of all blood cell counts is warranted in light of
this case.
PMID- 17034540
TI - Childhood epidermolysis bullosa acquisita with autoantibodies against the
noncollagenous 1 and 2 domains of type VII collagen: case report and review of
the literature.
AB - Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disease
characterized by IgG autoantibodies to type VII collagen, a major component of
anchoring fibrils. Most patients with EBA are adult and develop autoantibodies to
the noncollagenous (NC) 1 domain of type VII collagen. We describe a 4-year-old
Japanese boy presenting pruritic vesicles and tense blisters over his whole body.
Immunofluorescence studies revealed linear IgG/C3 deposits along the dermal
epidermal junction of the patient's skin, and circulating IgG autoantibodies
mapping to the dermal side of 1 M NaCl-split skin. By immunoblotting analysis
using dermal extracts as a substrate, the patient's IgG antibodies labelled a 290
kDa protein corresponding to type VII collagen. Immunoblotting studies using
recombinant proteins demonstrated that the patient's circulating autoantibodies
recognized not only the NC1 but also the NC2 domain of type VII procollagen.
Review of the previously reported cases and the present case suggested that
patients with EBA with autoantibodies to regions other than the NC1 domain are
all children younger than 10 years of age with clinical features of an
inflammatory phenotype.
PMID- 17034541
TI - Late lethal hepatitis B virus reactivation after rituximab treatment of low-grade
cutaneous B-cell lymphoma.
AB - The chimeric anti-CD20 monoclonal antibody, rituximab, is a promising treatment
for cutaneous B-cell lymphomas. Classically used in combination with a multiagent
chemotherapy regimen, it can sometimes give excellent results alone. Because of
its selective action on B lymphocytes, it is considered a moderate
immunosuppressant in terms of infection. We describe a woman with relapsed
cutaneous follicular centre B-cell lymphoma and secondary lymph-node involvement
treated with rituximab alone, which induced a complete remission. One year later,
she experienced a fatal hepatitis B virus (HBV) reactivation. Several such HBV
reactivations were reported after combined rituximab and multiagent chemotherapy
for B-cell lymphomas. This is the first case of HBV reactivation occurring during
the year following rituximab monotherapy in the absence of any other
immunosuppressive factor.
PMID- 17034542
TI - Poikiloderma, tendon contracture and pulmonary fibrosis: a new autosomal dominant
syndrome?
AB - Members of two generations of a South African family have a unique syndrome
comprising poikiloderma, tendon contractures and progressive pulmonary fibrosis.
The condition is clinically important as the skin changes, which involve the
face, have considerable cosmetic impact, while lung involvement is potentially
lethal in adulthood. Skin manifestations which facilitate diagnosis include
facial telangiectasia, mottled hypo- and hyperpigmentation, papules and epidermal
atrophy. The scalp, facial and body hair are fine and scanty. The tendon
contractures lead to progressive digital flexion deformities and abnormalities of
the ankles and feet, with disturbance of gait. Pulmonary involvement manifests as
progressive dyspnoea. Pedigree data are compatible with an autosomal dominant
mode of transmission. Poikiloderma of Weary is characterized by linear sclerotic
and fibrous bands and not tendon contractures and is not associated with
potentially lethal pulmonary fibrosis. Rather than name this disorder a variant
of Weary syndrome, it might be prudent to use as an umbrella title one composed
by Weary himself: 'hereditary sclerosing poikiloderma' (HSP), under which
variants such as HSP Weary type, HSP with cardiac involvement (aortic stenosis
described as inconsistently associated with Weary syndrome) and HSP with
tendon/pulmonary involvement (current family) may be classified. The
manifestations in this family differ from other poikilodermata and, to the best
of our knowledge, have not been previously documented.
PMID- 17034543
TI - A case of epidermolysis bullosa simplex with a newly found missense mutation and
polymorphism in the highly conserved helix termination motif among type I
keratins, which was previously reported as a pathogenic missense mutation.
PMID- 17034544
TI - A novel ABCA12 mutation 3270delT causes harlequin ichthyosis.
PMID- 17034545
TI - A novel familial germline mutation in the initiator codon of the BHD gene in a
patient with Birt-Hogg-Dube syndrome.
PMID- 17034546
TI - Two novel TSC2 mutations in Chinese patients with tuberous sclerosis complex and
a literature review of 20 patients reported in China.
PMID- 17034547
TI - Penile argyria.
PMID- 17034548
TI - Fatal erosive lichen planus.
PMID- 17034549
TI - Two cases of delayed granulomatous reactions to the cosmetic filler Dermalive, a
hyaluronic acid and acrylic hydrogel.
PMID- 17034550
TI - Highly active antiretroviral therapy-induced regression of basal cell carcinomas
in a patient with acquired immunodeficiency and Gorlin syndrome.
PMID- 17034551
TI - Management of onychomycosis and awareness of guidelines among dermatologists.
PMID- 17034552
TI - Phaeohyphomycosis caused by Exophiala salmonis.
PMID- 17034553
TI - Presence of herpes simplex virus DNA in erythema multiforme but not polymorphic
light eruption.
PMID- 17034554
TI - Successful treatment of stucco keratosis with maxacalcitol.
PMID- 17034555
TI - Eosinophilic cellulitis as a presenting feature of chronic eosinophilic
leukaemia, secondary to a deletion on chromosome 4q12 creating the FIP1L1-PDGFRA
fusion gene.
PMID- 17034556
TI - Neutrophilic dermatosis of the dorsal hands treated with indomethacin.
PMID- 17034557
TI - Alopecia areata associated with basal cell carcinoma developing within a naevus
sebaceus.
PMID- 17034558
TI - Low-resolution teledermatology.
PMID- 17034559
TI - Filaggrin loss-of-function variant contributes to atopic dermatitis risk in the
population of Northern Germany.
PMID- 17034561
TI - Proteus syndrome with agenesis of the rectus abdominis.
PMID- 17034562
TI - Ustilago species infection in humans.
PMID- 17034563
TI - Mycobacterium chelonae infection complicating cosmetic facial surgery.
PMID- 17034564
TI - Sweet syndrome: vasculitis or not?
PMID- 17034565
TI - Gefitinib-induced acute generalized exanthematous pustulosis in two patients with
advanced non-small-cell lung cancer.
PMID- 17034566
TI - Sweet syndrome associated with intrahepatic cholangiocarcinoma producing
granulocyte colony-stimulating factor.
PMID- 17034567
TI - Long-term infliximab for severe hidradenitis suppurativa.
PMID- 17034569
TI - Functional roles of immature dendritic cells in impaired immunity of solid tumour
and their targeted strategies for provoking tumour immunity.
AB - Dendritic cells play a crucial role in initiating tumour immunity as well as in
the immune response for invading foreign pathogens such as bacteria and viruses.
For bacterial and viral infections, the immature dendritic cells (iDCs) residing
in peripheral tissues are efficiently activated and matured by pathogen signals
for performing the immune response. In contrast, for self-antigens, the naive T
cells are not activated by iDCs but proceed to anergy/deletion, and the
generation of regulatory T cells for immune tolerance. The induction of immune
response and tolerance is regulated strictly by iDCs as the sensor for
homeostasis of immune response in the host. Despite the identification of some
tumour antigens, tumour immunity is not provoked successfully. Even though there
are some critical obstacles to inhibit effective tumour immunity, tumour cells
are able to exploit the functional roles of iDCs for tumour progression, which
are induced by tumour-derived soluble factors such as vascular endothelial growth
factor (VEGF) and functionally modulated in the microenvironment. The iDCs still
remain as the critical target for provoking tumour immunity. In this review, the
functional roles of tumour-associated iDCs and the strategy for targeting iDCs in
effective tumour immunity for the cancer patient are discussed.
PMID- 17034570
TI - Chronic Chlamydia pneumoniae infection may promote coronary artery disease in
humans through enhancing secretion of interleukin-4.
AB - Atherosclerosis is an inflammatory response, probably to a range of initiating
causes. Chronic infection with Chlamydia pneumoniae (C.pn) has been suggested as
one cause, but the nature of the association is controversial, in large part due
to lack of an identified mechanism to link infection with the atherosclerotic
process in man. This study examined 139 consecutive subjects with stable chest
pain, with the aim of correlating the serological status of C.pn infection with
the pattern of secretion of cytokines from CD4(+) T lymphocytes. C.pn
seropositive subjects secreted significantly more interleukin (IL)-4 than did
those who were C.pn seronegative (P = 0.02). No significant difference was noted
for secreted interferon (IFN)-gamma. The amount of secreted IL-4, but not of
secreted IFN-gamma, correlated positively with the extent of coronary artery
disease (P = 0.006). A similar correlation with secreted IL-4 was not identified
with Helicobacter pylori infection. These results support the hypothesis that
C.pn infection contributes to the inflammatory process responsible for coronary
artery atherosclerosis. The method used to detect cytokine secretion involves
ligation of CD40L on blood CD4(+) T cells, which may have relevance to tissue
events.
PMID- 17034571
TI - Identification of key peptide-specific CD4+ T cell responses to human
cytomegalovirus: implications for tracking antiviral populations.
AB - Human cytomegalovirus (CMV) infection is normally controlled effectively by the
immune response, including CD4(+) T cells. Large numbers of these cells are
present in healthy seropositive individuals but their loss in immunosuppression
leads to reactivation and disease. Tracking such responses in vivo is hampered by
poor definition of their peptide targets. In this study, we defined the key
targets of the peptide-specific CD4(+) T cell responses to the CMV pp65 protein
using functional assays and a peptide library. Despite a good deal of
interindividual variation in the numbers of peptides recognized, responses to CMV
pp65 were strikingly targeted at three key epitopes. A response to one or more of
these three key peptides was seen in all individuals tested (P < 0.0001) and this
finding was tested and reproduced in a second independent population. The most
common response identified was that to a DR53 restricted epitope, aa281-295. HLA
DR1 restricted CMV pp65-specific populations, although reproducibly detected,
were of low frequency ex vivo. However, it was possible to detect and phenotype
these cells using an enrichment protocol and this revealed them to have 'effector
memory' status although, in contrast to CD8(+) T cell responses, these were
CD45RA(-). These data suggest that CD4(+) T cell responses to CMV can be
identified reliably using a pool of just three peptides. This simple approach
will provide a robust and reliable as well as economic method for tracking
peptide specific populations in health and disease.
PMID- 17034572
TI - Quantitative measurement of hepatitis C virus core antigen is affected by the
presence of cryoglobulins.
AB - Mixed cryoglobulinaemia is associated strikingly with HCV infection. The aim of
this study was to assess whether the adherence to proper methods of collecting
samples for cryoglobulin detection was critical or not on virological parameters
in hepatitis C virus (HCV) patients. We studied 56 consecutive patients. Blood
samples were collected using a conventional method and a blood collection method
at 37 degrees C adapted to cryoglobulin detection. HCV core antigen and HCV RNA
were measured in sera and cryoglobulins issued from both blood collection
methods. In cryoglobulin-positive patients, serum concentrations of HCV core
antigen, but not that of HCV RNA, were significantly higher when a conventional
method was used, compared to a blood collection method at 37 degrees C (P =
0.001). In the cryoprecipitates, concentration of HCV core antigen was optimum
when the blood collection method at 37 degrees C, rather than the conventional
method, was applied for cryoglobulin detection (P < 10(-4)). The recovery of HCV
core antigen in the cryoprecipitate was improved when cryoglobulins were isolated
using the blood collection method at 37 degrees C rather than the conventional
method (P < 0.001). HCV parameter measurements and cryoglobulin study should not
be performed on the same serum samples due to the potential impact of blood
collection methods on results.
PMID- 17034573
TI - Innate immune peptide LL-37 displays distinct expression pattern from beta
defensins in inflamed gingival tissue.
AB - Anti-microbial peptides produced from mucosal epithelium appear to play pivotal
roles in the host innate immune defence system in the oral cavity. In particular,
human beta-defensins (hBDs) and the cathelicidin-type anti-microbial peptide, LL
37, were reported to kill periodontal disease-associated bacteria. In contrast to
well-studied hBDs, little is known about the expression profiles of LL-37 in
gingival tissue. In this study, the anti-microbial peptides expressed in gingival
tissue were analysed using immunohistochemistry and enxyme-linked immunosorbent
assay (ELISA). Immunohistochemistry revealed that neutrophils expressed only LL
37, but not hBD-2 or hBD-3, and that such expression was prominent in the
inflammatory lesions when compared to healthy gingivae which showed very few or
no LL-37 expressing neutrophils. Gingival epithelial cells (GEC), however,
expressed all three examined anti-microbial peptides, irrespective of the
presence or absence of inflammation. Moreover, as determined by ELISA, the
concentration of LL-37 in the gingival tissue homogenates determined was
correlated positively with the depth of the gingival crevice. Stimulation with
periodontal bacteria in vitro induced both hBD-2 and LL-37 expressions by GEC,
whereas peripheral blood neutrophils produced only LL-37 production, but not hBD
2, in response to the bacterial stimulation. These findings suggest that LL-37
displays distinct expression patterns from those of hBDs in gingival tissue.
PMID- 17034574
TI - Proviral load and immune markers associated with human T-lymphotropic virus type
1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Peru.
AB - Human T-lymphotropic virus type 1 (HTLV-1) is the aetiological agent of HTLV-1
associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of
this study is to identify which ex vivo and in vivo markers are associated
independently with HAM/TSP in a Peruvian population. Eighty-one subjects (33
men/48 women) were enrolled: 35 presented with HAM/TSP, 33 were asymptomatic HTLV
1 carriers (ACs) and 13 were HTLV-1-seronegative controls (SCs). Ex vivo markers
included T cell proliferation and Th1 [interferon (IFN)-gamma], Th2 [interleukin
(IL)-4, IL-5], proinflammatory [tumour necrosis factor (TNF)-alpha] and anti
inflammatory (IL-10) cytokine production in non-stimulated peripheral blood
mononuclear cell (PBMC) cultures. In vivo CD4(+) T cell count, markers of Th1
[interferon-inducible protein (IP)-10] and Th2 (sCD30) activity in plasma and
HTLV-1 proviral load in PBMCs were also evaluated. In univariate analysis,
several markers, including T cell proliferation, IFN-gamma, IP-10, sCD30 and
proviral load were associated with HAM/TSP, but in a multiple logistic regression
analysis only the proviral load remained associated significantly with disease
manifestation [adjusted OR 9.10 (1.24-66.91)]. Our findings suggest that HAM/TSP
is associated primarily with proviral load, whereas the observed association with
some immune markers seems secondary.
PMID- 17034575
TI - The T cell response to persistent herpes virus infections in common variable
immunodeficiency.
AB - We show that at least half of patients with common variable immunodeficiency
(CVID) have circulating CD8(+) T cells specific for epitopes derived from
cytomegalovirus (CMV) and/or the Epstein-Barr virus (EBV). Compared to healthy
age-matched subjects, more CD8(+) T cells in CVID patients were committed to CMV.
Despite previous reports of defects in antigen presentation and cellular immunity
in CVID, specific CD4(+) and CD8(+) T cells produced interferon (IFN)-gamma after
stimulation with CMV peptides, and peripheral blood mononuclear cells secreted
perforin in response to these antigens. In CVID patients we found an association
between a high percentage of circulating CD8(+) CD57(+) T cells containing
perforin, CMV infection and a low CD4/CD8 ratio, suggesting that CMV may have a
major role in the T cell abnormalities described previously in this disease. We
also show preliminary evidence that CMV contributes to the previously unexplained
severe enteropathy that occurs in about 5% of patients.
PMID- 17034576
TI - Immune markers measured before treatment predict outcome of intensive phase
tuberculosis therapy.
AB - The development of a statistical model based on simple immunological markers
which could predict the response to tuberculosis treatment would facilitate
clinical trials of new anti-tuberculosis drugs. We have examined the ability of
immunological biomarkers, measured at diagnosis and after 4 weeks of treatment,
to predict sputum smear status at week 8. Eighteen tuberculosis patients with
positive Ziehl-Nielsen (ZN)-stained sputum smears 8 weeks after initiation of
treatment (slow response) were matched for age, gender, sputum smear grade and
extent of disease on chest radiograph to 18 patients with negative sputum smears
at week 8 (fast response). In addition to total white blood cell (WBC) counts and
absolute lymphocyte, monocyte and neutrophil numbers, concentrations of six serum
markers were measured by enzyme-linked immunosorbent assay (ELISA) in all
patients (soluble interleukin-2 receptor alpha (sIL-2Ralpha), granzyme B, soluble
tumour necrosis factor alpha receptors 1 and 2 (sTNF-R1 and -2), nitrotyrosine
and interferon-gamma (IFN-gamma). At diagnosis, 4 biomarkers (sTNF-R1, total WBC,
absolute monocyte and absolute neutrophil numbers) were significantly higher in
slow response patients. At week 4, total WBC count and absolute monocyte and
neutrophil numbers remained significantly higher in slow responders. Discriminant
analysis of the diagnosis and week 4 data provided models for classification of
slow response patients with 67% and 83% predictive accuracy. We suggest that
treatment response phenotypes can be determined before the start of treatment.
Reliable predictive models would allow targeted interventions for patients at
risk for slow treatment response to standard tuberculosis therapy.
PMID- 17034577
TI - Expression and function of the purinergic receptor P2X7 in patients with
pulmonary tuberculosis.
AB - P2X(7) is a channel receptor gated by adenosine triphosphate (ATP) that is
involved in the killing of intracellular mycobacteria. To explore further the
role of P2X(7) in immunity against Mycobacterium tuberculosis, we studied its
expression and function in 19 patients with pulmonary tuberculosis (TB) and 19
healthy contacts. Flow cytometry analysis showed a similar and variable
expression of P2X(7) in TB patients and healthy subjects. In contrast, P2X(7)
mARN levels were significantly higher in TB patients. When the function of the
P2X(7) receptor in peripheral blood mononuclear cells (PBMC) was assessed by the
effect of exogenous ATP on apoptosis, the uptake of the fluorescent marker
Lucifer yellow or extracellular signal regulated kinase (ERK) phosphorylation, no
significant differences were detected in patients and controls. However, mRNA
macroarray analysis showed that upon stimulation with ATP, the PBMC from TB
patients showed a significant induction of a higher number of cytokine genes (27
of 96), and a lower number of apoptosis genes (20 of 96) compared to healthy
controls (17 and 76 genes, respectively). These results suggest that although the
PBMC from TB patients do not show apparent abnormalities in the expression of
P2X(7), and the intracellular signals generated through it, the pattern of gene
expression induced by ATP in these cells is different from that found in healthy
contacts. This phenomenon suggests a defective function of P2X(7) in the immune
cells from TB patients, a condition that may contribute to the inability of these
patients to eliminate the mycobacteria.
PMID- 17034578
TI - Autoantibodies against CD28 are associated with atopic diseases.
AB - The B7-1/B7-2-CD28/CTLA-4 pathway is crucial in regulating T cell activation and
tolerance. Autoantibodies to surface molecules on lymphocytes have already been
described in various immune conditions, such as autoimmune diseases, infections
and blood transfusions. The objective of this study was to test sera from healthy
individuals and from patients for association of CD28 autoantibodies with
inflammatory and non-inflammatory diseases. First, CD28 was obtained by digestion
of CD28-Ig fusion protein with trypsin. The cleavage products were separated by
sodium dodecyl sulphate-page gel electrophoresis. Additionally, a CD28/GST fusion
protein was expressed in Escherichia coli and was used to establish an enzyme
linked immunosorbent assay for detection of autoantibodies against CD28. Sera
from healthy individuals (n = 72) and patients with different inflammatory and
non-inflammatory skin diseases (n = 196) were tested for the presence of
autoantibodies against CD28. Using mixed lymphocyte reaction (MLR), purified
autoantibodies against CD28 were tested for their effects on CTLA-4-Ig-induced T
cell anergy. In this study, for the first time, we describe the existence of
autoantibodies against CD28 in humans which are associated with atopic diseases,
e.g. allergic rhinitis and asthma. These antibodies stimulate T cells and
overcome the CTLA-4-Ig-induced anergy of T cells in an MLR. The existence of
autoantibodies against CD28, which may have a T cell-stimulating function, has
been shown. The data indicate that autoantibodies against CD28 could be a new
immunological mechanism in allergic inflammation. Additionally, autoantibodies
against CD28 could be an important new marker to discriminate between atopic
diseases and other inflammatory skin diseases.
PMID- 17034579
TI - T cell receptor excision circles (TRECs), CD4+, CD8+, and their CD45RO+, and
CD45RA+, subpopulations in hepatitis C virus (HCV)-HIV-co-infected patients
during treatment with interferon alpha plus ribavirin: analysis in a population
on effective antiretroviral therapy.
AB - Interferon (IFN)-alpha induced CD4(+) T lymphopenia is a toxic effect of the
treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus
(HIV)-co-infected patients. To increase the knowledge about this secondary
effect, we performed an analysis of the evolution of the T cell receptor excision
circles (TRECs), CD4(+) and CD8(+) T cells and of their CD45RO(+) and CD45RA(+)
subpopulations during the treatment of chronic hepatitis HCV with peginterferon
alpha (pegIFN-alpha) + ribavirin. Twenty HCV/HIV-co-infected patients, with
undetectable HIV load after highly active antiretroviral therapy (HAART), were
treated with pegIFN-alpha + ribavirin. TRECs were determined using real-time
polymerase chain reaction. CD4(+) and CD8(+) T cells and their CD45RO(+) and
CD45RA(+) subpopulations were analysed by two-colour flow cytometry. Median
baseline CD4(+) and CD8(+) T cells were 592 mm(3) and 874 mm(3), respectively.
Median baseline CD45RO(+) subpopulation was 48% for CD4(+) T and 57% for CD8(+) T
lymphocytes. A progressive decrease in both T cell populations, as well as of
their CD45RO(+) and CD45RA(+) subpopulations, was detected, with a difference
between the baseline and nadir levels approaching 50%. The evolution of T cell
populations and TRECs was independent of the response to the treatment. T
lymphocytes and their subpopulations returned to baseline levels at 24 weeks
after the end of treatment, with the exception of the T CD4(+) CD45RA(+)
subpopulation. The ratio of CD4(+) CD45RO(+)/CD4(+) CD45RA(+) increased from 0.89
(baseline) to 1.44 (24 weeks after the end of the therapy). TRECs/ml did not
return to the basal values. In conclusion, a significant reduction of CD4(+) and
CD8(+) T cells, and of their CD45RA(+) and CD45RO(+) subpopulations, in HIV/HCV
co-infected patients treated with pegIFN-alpha was observed. Both subpopulations
increased after the suppression of treatment, but the CD4(+) CD45RA subpopulation
did not reach the basal levels as a consequence, at least in part, of a decrease
in thymic production.
PMID- 17034580
TI - Complement membrane attack is required for endplate damage and clinical disease
in passive experimental myasthenia gravis in Lewis rats.
AB - Myasthenia gravis (MG) is a debilitating and potentially fatal neuromuscular
disease characterized by the generation of autoantibodies reactive with nicotinic
acetylcholine receptors (AChR) that cause loss of AChR from the neuromuscular
endplate with resultant failure of neuromuscular transmission. A role for
complement (C) in the pathology of human MG has been suggested based upon
identification of C activation products in plasma and deposited at the endplate
in MG. In the rat model, experimental autoimmune MG (EAMG), C depletion or
inhibition restricts clinical disease, further implicating C in pathology. The
mechanisms by which C activation drives pathology in MG and EAMG are unclear.
Here we provide further evidence implicating C and specifically the membrane
attack complex (MAC) in the Lewis rat passive EAMG model of MG. Rats deficient in
C6, an essential component of the MAC, were resistant to disease induction and
endplate destruction was reduced markedly compared to C6-sufficient controls.
After reconstitution with C6, disease severity and endplate destruction in the C6
deficient rats was equivalent to that in controls. The data confirm the essential
role of the MAC in the destruction of the endplate in EAMG and raise the prospect
of specific MAC inhibition as an alternative therapy in MG patients resistant to
conventional treatments.
PMID- 17034581
TI - Remission of collagen-induced arthritis is associated with high levels of
transforming growth factor-beta expression in the joint.
AB - Immunization of genetically susceptible strains of mice with heterologous type II
collagen leads to the induction of a self-limiting polyarthritis that begins to
subside around 10 days after onset of clinical disease. The aims of this study
were to compare pro- and anti-inflammatory cytokine expression in the joints
during the course of arthritis in order to identify cytokines involved in
spontaneous remission of arthritis. DBA/1 mice were immunized with type II
collagen and an immunohistochemical analysis of expression of proinflammatory
cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6]
and anti-inflammatory cytokines [IL-10, IL-1ra, transforming growth factor (TGF)
beta1, TGF-beta2 and TGF-beta3] in joints was carried out over the course of the
disease. Both pro- and anti-inflammatory cytokines were found to be expressed in
early arthritis. However, around 10 days after onset of arthritis, the level of
expression of proinflammatory cytokines declined while the level of expression of
anti-inflammatory cytokines, particularly TGF-beta1 and TGF-beta2, increased.
Surprisingly, TNF-alpha continued to be expressed at low levels during the period
of disease remission (30 days after onset). Blockade of TNF-alpha during the
period of disease remission had no effect on TGF-beta expression. This study
confirms that the level of inflammation in arthritis correlates strongly with the
balance of pro- and anti-inflammatory cytokine expression in the joints. Of the
anti-inflammatory cytokines studied, TGF-beta1 and TGF-beta2 predominate during
the time of disease remission, suggesting that these cytokines are involved in
regulating disease activity.
PMID- 17034583
TI - Phenotypic features of circulating leucocytes as immunological markers for
clinical status and bone marrow parasite density in dogs naturally infected by
Leishmania chagasi.
AB - Canine visceral leishmaniasis (CVL) manifests itself as a broad clinical spectrum
ranging from asymptomatic infection to patent severe disease. Despite relevant
findings suggesting changes on lymphocytes subsets regarding the CVL clinical
forms, it still remains to be elucidated whether a distinct phenotypic profile
would be correlated with degree of tissue parasite density. Herein, we have
assessed the correlation between the clinical status as well as the impact of
bone marrow parasite density on the phenotypic profile of peripheral blood
leucocytes in 40 Brazilian dogs naturally infected by Leishmania chagasi. Our
major findings describe the lower frequency of B cells and monocytes as the most
important markers of severe CVL. Our main statistically significant findings
reveal that the CD8(+) T cell subset reflects most accurately both the clinical
status and the overall bone marrow parasite density, as increased levels of
CD8(+) lymphocytes appeared as the major phenotypic feature of asymptomatic
disease and dogs bearing a low parasite load. Moreover, enhanced major
histocompatibility complex (MHC)-II density as well as a higher CD45RB/CD45RA
expression index seems to represent a key element to control disease morbidity.
The association between clinical status, bone marrow parasitism and CD8(+) T
cells re-emphasizes the role of the T cell-mediated immune response in the
resistance mechanisms during ongoing CVL. Higher levels of circulating T
lymphocytes (both CD4(+) and CD8(+) T cells) and lower MHC-II expression by
peripheral blood lymphocytes seem to be the key for the effective immunological
response, a hallmark of asymptomatic CVL.
PMID- 17034582
TI - The membrane attack pathway of complement drives pathology in passively induced
experimental autoimmune myasthenia gravis in mice.
AB - The human neuromuscular disease myasthenia gravis (MG) is characterized by the
generation of autoantibodies reactive with nicotinic acetylcholine receptors
(AChR) that cause loss of AChR from the neuromuscular end-plate with resultant
failure of neuromuscular transmission. A role for complement (C) in AChR loss has
been suggested based upon morphological identification of C at the end-plate in
MG and from the effects of C inhibition in murine models. Here we provide further
evidence implicating C, and specifically the membrane attack complex (MAC), in a
mouse model of MG. Mice deficient in the C regulators Daf1 and/or Cd59a were
tested in the model. Wild-type mice were resistant to disease while mice
deficient in Daf1 had mild disease symptoms with evidence of C activation and
AChR loss at end-plates. Cd59a-deficient mice had very mild disease with some
muscle inflammation and essentially undamaged end-plates. In contrast, mice
deficient in both C regulators developed a severe paralytic disease with marked
muscle inflammation and loss of end-plates. Inhibition of MAC assembly abrogated
clinical disease in these double-deficient mice, demonstrating conclusively that
MAC formation was driving pathology in the model. These findings provoke us to
suggest that current anti-C therapeutics targeting MAC assembly will be
beneficial in MG patients resistant to conventional therapies.
PMID- 17034584
TI - Alcohol-induced gastritis prevents oral tolerance induction in mice.
AB - Despite several reports on the immunological relationship between inflammatory
bowel diseases and immunoregulatory mechanisms in the gut, systematic studies
addressing the impact of inflammatory processes in the gastric mucosa on events,
such as oral tolerance, are still limited. Herein, we report the establishment of
a novel murine model of gastritis induced by short-term administration of
ethanol. The major immumological features of this clinical entity are
characterized, as well as its impact on the induction of oral tolerance. Our data
demonstrate that ethanol ingestion during 4 consecutive days triggered an acute
inflammatory reaction in the stomach referred as ethanol-induced gastritis and
characterized by hyperaemia, oedema and mixed mononuclear/polymorphonuclear cell
infiltrate. Besides local immunological changes, such as high levels of gastric
interleukin (IL)-4 and interferon (IFN)-gamma, systemic alterations are also
observed, including increased IL-4 synthesis, enhanced levels of serum IgE and
absence of IL-10 production by spleen cells. Moreover, ethanol-induced gastritis
prevents oral tolerance induction to ovalbumin (OVA) as demonstrated by unaltered
anti-OVA humoral and cellular immune responses in treated animals. Tissue
eosinophilia after footpad immunization with OVA suggests that oral treatment
with ethanol induced an allergic-type reaction. Taken together, our findings
indicate that short-term ethanol ingestion is associated with gastric
inflammatory events able to break immunoregulatory mechanisms that maintain
mucosal homeostasis and oral tolerance.
PMID- 17034585
TI - The myeloid differentiation factor 88 is dispensable for the development of a
delayed host response to Pseudomonas aeruginosa lung infection in mice.
AB - Because MyD88 transduces a core set of Toll-like receptor (TLR)-induced signals,
microbial-induced host responses can be divided broadly into the MyD88-dependent
and MyD88-independent pathways. A specific pathogen induces a distinct pattern of
host response dependent upon the signalling pathways employed. Recently, we
demonstrated that a MyD88-dependent pathway is essential for the development of
early (4-8 h) host response to Pseudomonas aeruginosa lung infection. Here, we
show that the development of a delayed (24-48 h) host response to P. aeruginosa
is independent of MyD88. Using MyD88-deficient mice, the production of macrophage
inflammatory protein 2, tumour necrosis factor and interleukin 1alpha in the
airway was observed following P. aeruginosa lung infection for 24 or 48 h.
Moreover, the MyD88-deficient mice recruited sufficient neutrophils in the lung
and cleared the bacteria efficiently from the lung after 48 h. Thus, the full
development of host responses to P. aeruginosa lung infection involves, in a
sequential, stepwise fashion, a MyD88-dependent early response and a MyD88
independent delayed mechanism.
PMID- 17034586
TI - Interferon-gamma is causatively involved in experimental inflammatory bowel
disease in mice.
AB - Cytokines may be crucially involved in the pathogenesis of inflammatory bowel
diseases (IBD), but it remains controversial whether interferon (IFN)-gamma, a
typical proinflammatory cytokine, is an essential mediator to cause the
disorders. In the present study, IFN-gamma(-/-) and wild-type (WT) C57BL/6 mice
were fed 2.5% dextran sodium sulphate (DSS) in drinking water for 7 days, in
order to investigate DSS-induced intestinal inflammation. The DSS-treated WT mice
exhibited a robust production of IFN-gamma in the gut, a remarkable loss of body
weight, as well as high rate of mortality (60%). In striking contrast, IFN-gamma
deficient mice did not develop DSS-induced colitis, as indicated by the
maintenance of body weight and survival rate of 100%. Severe intestinal
inflammation was demonstrated exclusively in WT animals in terms of the
shortening of the bowel as well as the elevation of the disease activity index,
myeloperoxidase (MPO) activity and serum haptoglobin level. Histological study of
DSS-treated WT intestine revealed disruption of mucosal epithelium and massive
infiltration of inflammatory cells, while the organ from IFN-gamma(-/-) mice
remained virtually normal in appearance. Enzyme-linked immunosorbent assay
(ELISA) analyses indicated abundant production of three chemokines, i.e. monokine
induced by interferon-gamma (MIG), interferon-inducible protein 10 (IP-10) and
monocyte chemoattractant protein-1 (MCP-1), in the DSS-irritated intestine of WT
but not of IFN-gamma(-/-) mice. The present results demonstrate clearly that IFN
gamma plays indispensable roles in the initiation of DSS colitis, and some
chemokines are produced in an IFN-gamma-dependent fashion.
PMID- 17034587
TI - Glomerular expression and elevated serum Bcl-2 and Fas proteins in lupus
nephritis: preliminary findings.
AB - Programmed cell death (apoptosis) is involved in glomerular injuries leading to
glomerulonephritis. Bcl-2 and Fas are proteins that promote cell survival and
death, respectively. This study tests the hypothesis that lupus nephritis is
associated with alterations of Bcl-2 and Fas protein expression. Thirty-six
patients with lupus nephritis and 10 controls (normal individuals) were included
in this study. Bcl-2 and Fas positive cells were examined in kidney biopsies by
immunohistochemistry. Bcl-2 and Fas serum levels were evaluated by enzyme-linked
immunosorbent assay (ELISA). In the glomeruli of normal kidneys, Bcl-2 and Fas
proteins were completely absent. In lupus nephritis patients, glomerular
expression of Bcl-2 and Fas was seen in mesangial cells (1.3 +/- 0.1 and 2.0 +/-
0.1 for Bcl-2 and Fas, respectively). Similarly, a statistically significantly
higher Bcl-2 (217.1 +/- 85.9) and Fas (767.9 +/- 271) serum levels were found in
lupus patients compared to controls (148.6 +/- 87, 550.3 +/- 91 for Bcl-2 and
Fas, P < 0.05). A direct correlation between serum Bcl-2 and Fas and chronicity
index was also found. Compared to normal controls, lupus nephritis is associated
with glomerular expression and elevated serum levels of Bcl-2 and Fas proteins.
These findings suggest possible roles for Bcl-2 and Fas in glomerular injury
during evolution of lupus nephritis. The diagnostic, prognostic and therapeutic
ramifications of our findings are open to further investigation.
PMID- 17034588
TI - The highly attenuated vaccinia virus strain modified virus Ankara induces
apoptosis in melanoma cells and allows bystander dendritic cells to generate a
potent anti-tumoral immunity.
AB - Vaccinia virus (VV) has been tested as oncolytic virus against malignant melanoma
in clinical trials for more than 40 years. Until now, mainly strains comparable
to viral strains used for smallpox vaccination have been probed for anti-tumoral
therapy. We have shown recently that the wild-type strain Western Reserve (WR)
can interfere with crucial functions of monocyte-derived dendritic cells (DCs).
Our aim was to examine whether viral immune evasion mechanisms might be
responsible for the ineffectiveness of WR-based vaccination strategies and
whether the highly attenuated strain modified virus Ankara (MVA) differs from WR
with respect to its possible immunostimulatory capacity after intratumoral
injection. Using in vitro experiments, we compared the effect of both strains on
melanoma cells and on local bystander DCs. We found that both VV-strains infected
melanoma cells efficiently and caused disintegration of the actin cytoskeleton,
as shown by fluorescence microscopy. In addition, both VV-strains caused
apoptotic cell death in melanoma cells after infection. In contrast to MVA, WR
underwent a complete viral replication cycle in melanoma cells. Bystander DCs
were consecutively infected by newly generated WR virions and lost their capacity
to induce allogeneic T cell proliferation. DCs in contact with MVA-infected
melanoma cells retained their capacity to induce T cell proliferation. Immature
DCs were capable of phagocytosing MVA-infected melanoma cells. Priming of
autologous CD8(+) T cells by DCs that had phagocytosed MVA-infected, MelanA
positive melanoma cells resulted in the induction of T cell clones specifically
reactive against the model antigen MelanA as shown by enzyme-linked immunospot
(ELISPOT) analysis. We conclude that the clinical trials with oncolytic wild-type
VV failed probably because of suppression of bystander DCs and consecutive
suppression of T cell-mediated anti-melanoma immunity. The attenuated VV-strain
MVA facilitates the generation of tumour associated antigen (TAA)-specific T cell
response as it is oncolytic for melanoma cells, but non-toxic for DC, and should
be a promising candidate for intralesional metastatic melanoma therapy.
PMID- 17034589
TI - Effect of serotonin on the differentiation of human monocytes into dendritic
cells.
AB - The local cytokine environment and presence of stimulatory signals determine
whether monocytes acquire dendritic cell (DC) or macrophage characteristics and
functions. Because enhanced platelet activation is reported in patients with many
allergic disorders, such as atopic dermatitis, platelet-derived factors may
influence monocytic differentiation into DC. In this study we examined the effect
of serotonin, a prototypic mediator of allergic inflammation released mainly by
activated platelets at the inflammatory site, on the granulocyte-macrophage
colony-stimulating factor (GM-CSF) and interleukin (IL)-4-driven differentiation
of monocytes into monocyte-derived DC. Monocytes from healthy adult donors were
cultured with GM-CSF and IL-4 in the presence or absence of serotonin, and the
phenotypes and function of these cells were analysed. In the presence of
serotonin, monocytes differentiated into DC with reduced expression of co
stimulatory molecules and CD1a, whereas expression of CD14 was increased. These
serotonin-treated DC exhibited significantly reduced stimulatory activity toward
allogeneic T cells. However, these cells showed enhanced cytokine-producing
capacity, including IL-10 but not IL-12. There was no significant difference
between both types of DC in phagocytic activity. Experiments using agonists and
antagonists indicated that serotonin 5-hydroxytryptamine (5-HT) induced the
alteration of their phenotype and reduction in antigen-presenting capacity were
mediated via 5-HTR(1/7). It is therefore suggested that serotonin-driven DC may
have a regulatory function in the inflammatory process.
PMID- 17034591
TI - Can prostate cancer targets be achieved?
PMID- 17034590
TI - Hypoxia induces expression of connective tissue growth factor in scleroderma skin
fibroblasts.
AB - Connective tissue growth factor (CTGF) plays a role in the fibrotic process of
systemic sclerosis (SSc). Because hypoxia is associated with fibrosis in several
profibrogenic conditions, we investigated whether CTGF expression in SSc
fibroblasts is regulated by hypoxia. Dermal fibroblasts from patients with SSc
and healthy controls were cultured in the presence of hypoxia or cobalt chloride
(CoCl(2)), a chemical inducer of hypoxia-inducible factor (HIF)-1alpha.
Expression of CTGF was evaluated by Northern and Western blot analyses. Dermal
fibroblasts exposed to hypoxia (1% O(2)) or CoCl(2) (1-100 microM) enhanced
expression of CTGF mRNA. Skin fibroblasts transfected with HIF-1alpha showed the
increased levels of CTGF protein and mRNA, as well as nuclear staining of HIF
1alpha, which was enhanced further by treatment of CoCl(2). Simultaneous
treatment of CoCl(2) and transforming growth factor (TGF)-beta additively
increased CTGF mRNA in dermal fibroblasts. Interferon-gamma inhibited the TGF
beta-induced CTGF mRNA expression dose-dependently in dermal fibroblasts, but
they failed to hamper the CoCl(2)-induced CTGF mRNA expression. In addition,
CoCl(2) treatment increased nuclear factor (NF)-kappaB binding activity for CTGF
mRNA, while decreasing IkappaBalpha expression in dermal fibroblasts. Our data
suggest that hypoxia, caused possibly by microvascular alterations, up-regulates
CTGF expression through the activation of HIF-1alpha in dermal fibroblasts of SSc
patients, and thereby contributes to the progression of skin fibrosis.
PMID- 17034592
TI - Urological cancer guidelines: are there any differences?
PMID- 17034593
TI - WWW; the wild, wild web: internet usage in patients with urological cancer.
PMID- 17034594
TI - Urological management of 'page kidney'.
PMID- 17034595
TI - Results of a definitive study are needed to provide guidance on the treatment of
patients with screen-detected, 'low-grade' prostate cancer.
PMID- 17034596
TI - The enlarged prostate: a brief history of its surgical treatment.
PMID- 17034597
TI - Congenital urethral obstruction: the video-endoscopic perspective.
PMID- 17034598
TI - Risk factors and prevention of rhabdomyolysis after laparoscopic nephrectomy.
PMID- 17034599
TI - Urinary symptom flare after brachytherapy for prostate cancer is associated with
erectile dysfunction and more urinary symptoms before implantation.
AB - OBJECTIVE: To examine the relationship of 'symptom flare' with sexual function
and lower urinary tract symptoms (LUTS) before brachytherapy, as we noted that
after brachytherapy for prostate cancer, some patients had recurrent LUTS after
an asymptomatic period; this secondary exacerbation of symptoms ('symptom flare')
occurred at approximately 2 years after implantation and was transient in most
patients. PATIENTS AND METHODS: In all, 854 patients with organ-confined prostate
carcinoma had transrectal ultrasonography-guided transperineal 125I interstitial
brachytherapy of the prostate gland between June 1991 and September 2002, and
were considered candidates for this study. Detailed information on urinary
function was self-administered and prospectively collected before treatment and
at intervals using the International Prostate Symptom Score (IPSS). Sexual
function was evaluated with the Sexual Health Inventory for Men (SHIM), a five
question, self-administered diagnostic test that can help to indicate the
presence or absence of erectile dysfunction (ED). We used previously established
criteria to estimate the risk of prostate-specific antigen (PSA) failure by
dividing the men into three risk groups, i.e. low-risk, with a PSA level of < or
= 10 ng/mL, stage < or = T2a, Gleason < or = 6; medium-risk, with a PSA level of
< or = 15 ng/mL, Gleason 7 or stage T2b; and high-risk, with a PSA level of > 15
ng/mL, stage > T2b, or Gleason > or = 8. RESULTS: There was a significant
association of flare with ED; men with flare reported significantly more ED than
men without (P = 0.020). Men with high-risk disease reported more ED because they
received more intensive treatment (hormones and increased radiation dose) than
men with medium- or low-risk disease. To correct for this confounding factor,
multivariate linear regression was used; the regression was significant overall
(P < 0.001), and the effects of risk group (P < 0.001) and flare (P < 0.026) on
SHIM score were significant and independent of each other. Flare was also
significantly associated with a higher pre-implant IPSS; the probability of flare
was 62% for a pre-implant IPSS of zero, to 94% for an IPSS of 30. CONCLUSIONS:
Radiation reaction and radiation sensitivity contribute to ED and greater LUTS in
men who have had brachytherapy for prostate cancer. This contribution is evident,
e.g. in men with ataxia-telangiectasia (ATM) gene mutations. Sequence variants in
the ATM gene, particularly those that encode for an amino-acid substitution, are
associated with adverse radiotherapy responses among patients treated with 125I
prostate brachytherapy. Our finding of the association of urinary symptom flare
with ED suggests it would be worthwhile to determine whether sildenafil is as
effective in men with flare, and if not, whether higher sildenafil doses would be
of value. Alternatively, alpha1-selective adrenoceptor-blocking agents, e.g.
terazosin, combined with sildenafil, might be of benefit. Also, patients with a
high IPSS before brachytherapy can be warned that they have a greater risk of
flare and ED.
PMID- 17034600
TI - Predictive value of prostatic adenocarcinoma after a negative prostate biopsy.
AB - OBJECTIVE: To investigate the predictive value (PV) for all prostate cancers and
for clinically significant cancer undiagnosed after a 10-core biopsy protocol, as
the 10-core transrectal ultrasonography-guided biopsy is considered the standard
technique of prostatic biopsy due to its high rate of detection of prostatic
adenocarcinoma. PATIENTS AND METHODS: In all, 132 consecutive radical
prostatectomy (RP) specimens, with their corresponding 10-core biopsies, were
reviewed. Cases with unilateral core involvement by prostate cancer were retained
for study. Morphometric analysis was conducted on the biopsy-negative hemi
prostates to determine the PV of the biopsy protocol with respect to the size,
position and clinical significance of the lesion. RESULTS: In all, 70 resected
prostates (RP) had unilateral core involvement by prostate cancer. In 38 cases,
there was cancer in the biopsy-negative hemi-prostates (group 1); in the
remaining 32 the hemi-prostates were free of cancer (group 2). Group 1 was
categorized by morphometric criteria. Specifically, 23 cases had one to eight
foci of prostate cancer in the posterior nontransitional zone (NTZ) (group 1a),
while 15 had two to six foci of prostate cancer in the transitional zone (TZ), or
the anterior horn (AH) of the peripheral zone or the TZ and AH (group 1b). There
were two cases with clinically significant prostate cancer in group 1a, and six
in group 1b. CONCLUSIONS: The PV of a negative five-core biopsy protocol on a
hemi-prostate is 54% for prostate cancer and 11% for clinically significant
prostate cancer. Most clinically significant prostate cancers were in the AH/TZ
of the prostate.
PMID- 17034601
TI - Prostate-specific antigen testing: uncovering primary care influences.
AB - OBJECTIVES: To examine influences on the behaviour of General Practitioner (GP)
in relation to prostate-specific antigen (PSA) testing. SUBJECTS AND METHODS: In
Northern Ireland in 2003-2004, all GPs (1067) were invited to complete a self
administered postal questionnaire survey that was then matched with a regional
PSA-testing database. The main outcome measures were individual GP responses for
demographic, practice and training characteristics, PSA testing behaviour and
perceived influences, matched against GP-initiated first PSA tests performed in
2003 and 2004 (22 207 tests). RESULTS: In all, 704 GPs (66%) responded and 49% of
these reported awareness of the national guidelines, which was highest among
those attending postgraduate meetings. PSA tests were more likely to be ordered
by full-time male GPs who had attended a local postgraduate urology meeting; ran
a 'well-man' clinic; tested men with unrelated complaints; and were not in a
training practice. Testing levels were highest among GPs who had been practising
for 21-30 years and those in rural practices. Awareness of national guidelines or
having had a postgraduate post in urology did not affect testing behaviour. After
adjusting for gender, working hours, duration in practice and urban/rural
setting, independent influences increasing testing behaviour were: testing men
with a positive family history or unrelated complaints; testing any man who
requests it; and previous experience of prostate cancer being detected in an
asymptomatic patient by PSA testing. Working in an accredited training practice
was associated with lower testing levels. CONCLUSION: There are complex
influences on the PSA testing behaviour of GPs; addressing these influences could
contribute to the rationalization of testing. A low awareness of national
guidelines indicates a need for new strategies to disseminate and implement
guidelines. The influence of local educational meetings on PSA testing is an
unharnessed force.
PMID- 17034602
TI - Carefully selected intratesticular lesions can be safely managed with serial
ultrasonography.
AB - OBJECTIVE: To evaluate a policy of conservative non-operative management for
incidental, impalpable, < 1 cm, intratesticular pathology. PATIENTS AND METHODS:
We retrospectively reviewed all scrotal ultrasonograms within an 8-year period to
identify all radiological lesions of < 1 cm within the testis. All palpable
lesions and those accompanied by elevated tumour markers or disseminated
malignancy were managed surgically. The remaining incidentally detected lesions
were followed with a protocol of serial ultrasonography (US). RESULTS: Of 1544
scans reviewed, 12 (0.8%) lesions suitable for observational management were
identified. The mean (range) age of the patients was 54 (34-76) years. The
indication for US was suspected epididymitis in five, contralateral epididymal
cyst in five and infertility in two patients. The mean (range) size of the lesion
was 4.9 (1.5-9.8) mm. Three anechoic lesions were consistent with intratesticular
cysts, and each was followed with no change to a mean (range) follow-up of 26 (12
48) months. Eight hypoechoic lesions were followed to a mean of 34 (4-72) months,
and only one showed growth on repeat US after an interval of 4 months, and was
diagnosed as a 1.0-cm seminoma after orchidectomy. One hyperechoic lesion remains
unchanged at 6 months of follow-up. CONCLUSION: Supported by previous reports
suggesting that most testis lesions of < 1 cm are benign, we managed a series of
carefully selected intratesticular lesions conservatively, the behaviour in most
being in keeping with benign pathology.
PMID- 17034603
TI - Surgical treatment for urethral recurrence after ileal neobladder reconstruction
in patients with bladder cancer.
AB - OBJECTIVE: To report a retrospective study evaluating the management of
superficial urethral recurrence after ileal neobladder construction in patients
with bladder cancer. PATIENTS AND METHODS: In 77 consecutive patients with ileal
neobladder after radical cystectomy for invasive bladder cancer, urethral
recurrence was evaluated and transurethral resection (TUR) used as an initial
treatment for superficial urethral recurrence. Urethrectomy with urinary re
diversion was performed when further recurrence developed. RESULTS: Four patients
(5%) presented with a superficial urethral recurrence and all four were treated
by TUR as initial therapy. One patient has had no evidence of recurrence after
initial TUR, although the other three patients were later treated with salvage
urethrectomy due to repeated urethral recurrence. As a result, the stage of
urethral recurrence advanced from pTa to pT1-pT2 in two of the three patients.
For urinary re-diversion, one patient had a conversion from a Studer pouch to an
ileal conduit, using the afferent limb, and the other two were converted from a
Hautmann pouch to a continent reservoir using the Appe-Mainz procedure. There was
no evidence of metastasis or local recurrence in any of the four patients.
CONCLUSION: Urethral preservation at initial therapy for superficial recurrence
might be reasonable, and sequential urethrectomy after attempted urethral
preservation might be strategically feasible. Urinary re-diversion from a
neobladder to a catheterizable continent reservoir using the appendix would be a
good choice and maintains the quality of life.
PMID- 17034604
TI - Adjuvant intravesical therapy based on an in vitro cytotoxicity assay in the
management of superficial transitional cell cancer of the urinary bladder.
AB - OBJECTIVE: To investigate the utility of an individualized chemo/immunotherapy
regimen of intravesical therapy based on the results of an assessment of in vitro
cytotoxicity. PATIENTS AND METHODS: Intravesical adjuvant chemo/immunotherapy was
given to 47 patients based on the results of in vitro cytotoxicity assay of the
responses of cultured autologous tumour cells to various cytotoxic drugs
(mitomycin-C, doxorubicin and cisplatin) and immunomodulating agents (bacillus
Calmette-Guerin, BCG and interferon-alpha2b). Intravesical therapy was given as
single- or double-drug regimens according to the assay results: 16 (34%) patients
showed cytotoxicity to a single drug and 31 (66%) showed maximum cytotoxicity to
a combination of immunomodulators and cytotoxic agents. The efficacy of treatment
in terms of tumour-free survival and recurrence rate was compared with 40
patients receiving intravesical BCG according to International Protocol (control
group). RESULTS: In the in vitro assay group, seven patients (15%) had tumour
recurrence, compared to 15 (38%) in the control group (P = 0.02). In the in vitro
group, one of 16 patients on a single drug and six on the double-drug regimen had
a recurrence. The patients given BCG with cytotoxic drugs had no recurrences, but
29% of patients given interferon-alpha2b combinations had recurrences. Kaplan
Meier analysis showed a longer recurrence-free survival in the in vitro group
(75%) than in the control group (49%) at 48 months of follow-up. CONCLUSION:
Intravesical therapy based on an in vitro cytotoxicity assay is an attempt to
give individualized therapy, and to increase tumour-free survival in these
patients, with no side-effects. Recurrences in seven patients in the in vitro
group might be due to a defective host immune response, or to expansion of a
subclone of tumour cells resistant to all treatment.
PMID- 17034605
TI - A randomized controlled trial of the effectiveness of pelvic floor therapies for
urodynamic stress and mixed incontinence.
AB - OBJECTIVES: To assess the efficacy and cost-effectiveness of pelvic floor muscle
therapies (PFMT) in women aged > or = 40 years with urodynamic stress
incontinence (USI) and mixed UI. PATIENTS AND METHODS: In a three-arm randomized
controlled trial in Leicestershire and Rutland UK, 238 community-dwelling women
aged > or = 40 years with USI in whom previous primary behavioural intervention
had failed were randomized to receive either intensive PFMT (79), vaginal cone
therapy (80) or to continue with primary behavioural intervention (79) for 3
months. The main outcome measure was the frequency of primary UI episodes, and
secondary measures were pad-test urine loss, patient perception of problem,
assessment of PF function, voiding frequency, and pad usage. Validated scales for
urinary dysfunction, and impact on quality of life and satisfaction were
collected at an independent interview. RESULTS: All three groups had a moderate
reduction in UI episodes after intervention but there was no statistically
significant difference among the groups. There were marginal improvements in
voiding frequency for all groups, with no statistically significant difference
among them. CONCLUSIONS: In women who have already had simple behavioural
therapies (including advice on PFM exercises) for urinary dysfunction, the
continuation of these behavioural therapies can lead to further improvement. The
addition of vaginal cone therapy or intensive PFMT does not seem to contribute to
further improvement. The improvement in pelvic floor function was significantly
greater in the PFMT arm than in the control arm although this did not translate
into changes in urinary symptoms.
PMID- 17034606
TI - Does the clinical efficacy of vardenafil correlate with its effect on the
endothelial function of cavernosal arteries? A pilot study.
AB - OBJECTIVE: To investigate whether the results of the ultrasonographic (US)
measurement of post-occlusive changes in the diameters of cavernosal arteries
after administering phosphodiesterase type 5 (PDE-5) inhibitor vardenafil could
be associated with the response to vardenafil in patients with erectile
dysfunction (ED), as currently there are no reliable methods for predicting the
success rate of oral PDE-5 inhibitors. PATIENTS AND METHODS: The study included
122 men with ED; after a complex evaluation, the endothelial function of the
cavernosal arteries was assessed in all patients before and 1 h after oral
ingestion of vardenafil (20 mg), using our modification of the US assessment of
post-occlusive changes in the diameter of cavernosal arteries. After the
evaluation, all patients received vardenafil 20 mg on demand for 4 weeks. A
successful response was defined using two endpoints, i.e. the normalization of
the International Index of Erectile Function Erectile Function domain score (> or
= 26) and positive answers to both Sexual Encounter Profile questions 2 and 3 on
> or = 75% of occasions, based on the diary data collected. RESULTS: In all
patients the mean (sd) initial percentage increase in the cavernosal artery
diameter (PICAD) in responders and nonresponders was not statistically different,
at 49 (24) and 43 (26), respectively (P = 0.168), but PICAD values after
vardenafil were significantly greater in responders, at 73 (16) vs 55 (23) (P <
0.001). Analysis of data from patients with different causes of ED showed
statistically significant differences in PICAD between responders and
nonresponders only in those with arteriogenic ED. The sensitivity and specificity
of a PICAD of > or = 50% after taking vardenafil 20 mg for predicting a positive
response to the same dose of the drug in patients with arteriogenic ED were 94.9%
and 91.3%, respectively. CONCLUSION: The results of the US assessment of post
occlusive changes in the diameter of cavernosal arteries after vardenafil
administration are significantly associated with the clinical efficacy of the
drug in patients with arteriogenic ED.
PMID- 17034607
TI - Minimally invasive radical cystectomy.
PMID- 17034608
TI - One week of ciprofloxacin before percutaneous nephrolithotomy significantly
reduces upper tract infection and urosepsis: a prospective controlled study.
AB - OBJECTIVE: To evaluate whether 1 week of ciprofloxacin before percutaneous
nephrolithotomy (PCNL) in patients with stones of > or = 20 mm or pelvicalyceal
dilatation, reduces urosepsis, as we previously reported that such patients have
four times the risk of urosepsis after PCNL. PATIENTS AND METHODS: Patients
undergoing PCNL, and who fulfilled strict selection criteria, were recruited
prospectively into a study which was conducted in two phases. The study methods
were similar to those previously described; patients with dilated pelvicalyceal
systems and/or stones of > or = 20 mm from phase 1 (previously published) acted
as controls. In the subsequent phase, the same selection criteria applied and
only those with stones of > or = 20 mm and/or dilated pelvicalyceal systems were
given ciprofloxacin 250 mg twice daily for 1 week before PCNL and comprised the
treatment arm. Midstream urine samples, renal pelvic urine and fragmented stones
were collected to assess culture and sensitivity. Systemic inflammatory response
syndrome (SIRS) was used to define urosepsis after PCNL. The urologists
monitoring the patients after PCNL and conducting the analysis were all unaware
of the characteristics of the stones or intravenous urography findings before
PCNL. In all, 115 patients (54 in phase 1 and 61 in phase 2) were recruited, of
whom 46 in phase 1 and 52 in phase 2 had stones of > or = 20 mm and/or a dilated
pelvicalyceal system, and became the control and treatment arms, respectively.
RESULTS: The patient demographics were similar in both arms. There was three
times less risk of upper tract infection (relative risk 3.4, 95% confidence
interval 1.0-11.8, P = 0.04) and SIRS (2.9, 1.3-6.3, P = 0.004) in the patients
receiving ciprofloxacin (treatment arm). CONCLUSIONS: The administration of oral
ciprofloxacin for 1 week before PCNL in patients with stones of > or = 20 mm or
dilated pelvicalyceal systems significantly reduced the risk of urosepsis.
PMID- 17034609
TI - Vascular endothelial growth factor-C expression in bladder transitional cell
cancer and its relationship to lymph node metastasis.
AB - OBJECTIVE: To elucidate the role of vascular endothelial growth factor-C (VEGF-C)
in bladder transitional cell carcinoma (TCC), examining VEGF-C expression in
bladder TCC tissue and the association of VEGF-C with clinicopathological
features, as the expression of VEGF-C in several carcinomas is significantly
associated with angiogenesis, lymphangiogenesis and regional lymph node
metastasis, but there are few reports of VEGF-C expression in bladder TCC.
PATIENTS AND METHODS: The study included 45 patients with bladder TCC; VEGF-C
expression was assessed by immunohistochemistry and the association between VEGF
C expression and angiogenesis, as evaluated by microvessel density (MVD), was
examined. RESULTS: There was VEGF-C expression in the cytoplasm of tumour cells,
but very little in the normal transitional epithelium. VEGF-C expression was
significantly associated with tumour size, pathological T stage, pathological
grade, lymphatic-venous involvement and pelvic lymph node metastasis (all P <
0.05). Multivariate analysis showed that VEGF-C expression was an exclusive
independent factor influencing pelvic lymph node metastasis. Moreover, the
patients with high VEGF-C expression had a markedly poorer prognosis than those
with no or low VEGF-C expression (P = 0.014). A multivariate analysis based on
the Cox proportional hazard model showed that lymph node metastasis was only an
independent prognostic factor in the multivariate analysis using the Cox
regression model (P = 0.010). CONCLUSION: The present study provides evidence
supporting the involvement of VEGF-C expression in the promotion of lymph node
metastasis in bladder TCC. Examination of VEGF-C expression in biopsy specimens
might be beneficial in predicting pelvic lymph node metastasis.
PMID- 17034610
TI - Heat-shock protein 25 ameliorates calcium oxalate crystal-mediated oxidative
stress in renal epithelial cells.
AB - OBJECTIVE: To investigate whether the antioxidant protection attributed to small
heat-shock proteins (sHSPs) affects calcium oxalate stone formation, a pro
oxidant disease. MATERIALS AND METHODS: Canine distal tubular epithelial cells
(Madin-Darby canine kidney, MDCK cells) were grown as confluent monolayers.
Treatment regimens included control and HS-treated cells (37 degrees C and 42
degrees C for 1 h) with or without calcium oxalate monohydrate (COM) or free
oxalate treatment (28 microg/cm2) 16 h later. In digitonin-permeabilized cells,
O2- was measured by lucigenin-enhanced chemiluminescence over a 5-min period, to
measure mitochondrial O2- production. Protein expression was assessed by sodium
dodecyl sulphate-polyacrylamide gel electrophoresis Western blot analysis using
specific antibodies. RESULTS: COM significantly increased O2- production in MDCK
cells. HS treatment, which up-regulated HSP25 expression, significantly decreased
this O2- production (P < 0.05) but had no effect in control cells. In COM-treated
cells (20 h) there was a marked and significant down-regulation of both HSP 25,
HSP 70 and heme oxygenase-1 expression compared to cells treated with HS alone (P
< 0.05). Free oxalate had no effect on HSP 25 expression. CONCLUSIONS: The
results suggest that the COM-induced increase in mitochondrial O2- production in
MDCK cells is ameliorated by HSP 25 up-regulation via HS. Specific COM inhibition
of HSP 25, HSP 70 and heme oxygenase-1 up-regulation suggests that COM-induced
reactive oxygen species damage is unable to benefit from HSP-associated
physiological resistance.
PMID- 17034611
TI - Challenges in a larger bladder replacement with cell-seeded and unseeded small
intestinal submucosa grafts in a subtotal cystectomy model.
AB - OBJECTIVE: To evaluate small intestinal submucosa (SIS), unseeded or seeded, as a
possible augmentation material in a canine model of subtotal cystectomy.
MATERIALS AND METHODS: In all, 22 male dogs had a 90% partial cystectomy and were
then divided into three groups. At 1 month after the initial cystectomy, dogs in
group 1 (unseeded, six) and group 2 (seeded, six) received a bladder augmentation
with a corresponding SIS graft. The dogs in group 3 (ten) received no further
surgery and were considered the surgical control group. All dogs were evaluated
before and after surgery with blood chemistry, urine culture, intravenous
urography, cystograms and cystometrograms. After surgery (at 1, 5 and 9 months),
the bladders were examined using routine histology and immunohistochemistry.
RESULTS: All 22 dogs survived the subtotal cystectomy, and 18 survived their
intended survival period. One dog, in group 2 (seeded), was killed at 1 month
after augmentation due to bladder perforation caused by a large piece of
incompletely absorbed SIS. Three other dogs (group 1, two; and group 2, one) were
killed within 2 months after augmentation due to bladder obstruction by stones.
Group 1 and group 2 SIS grafts had moderate to heavy adhesion, graft shrinkage,
and some had bone and calcification at the graft site. Histologically, there was
limited bladder regeneration in both groups. Interestingly, dogs in group 3 at 1
month after cystectomy (when group 1 and 2 received their augmentations) had
severely shrunken bladders and histologically had severe inflammation, fibroblast
infiltration and muscle hypertrophy. These results verify the subtotal cystectomy
model. CONCLUSIONS: The use of seeded or unseeded SIS in a subtotal cystectomy
model does not induce the same quality and quantity of bladder regeneration that
is seen in the 40% non-inflammatory cystectomy model. This study provides
important insights into the process of regeneration in a severely damaged
bladder. The results led us to re-evaluate the critical elements required for a
complete bladder replacement using tissue-engineering techniques.
PMID- 17034612
TI - Pygeum africanum extract inhibits proliferation of human cultured prostatic
fibroblasts and myofibroblasts.
AB - OBJECTIVE: To investigate the effect of Pygeum africanum (PA) extract on the
proliferation of cultured human prostatic myofibroblasts and fibroblasts; this
extract is used for treating urinary disorders associated with benign prostatic
hyperplasia (BPH). MATERIALS AND METHODS: Primary cultures of prostatic stromal
cells were obtained from histologically confirmed human BPH by enzymatic
digestion. Cell proliferation was measured by 5-bromo2'-deoxy-uridine (BrdU)
incorporation assays, and cytotoxicity by luminescent quantification of adenylate
kinase activity. RESULTS: Cultured cells were labelled by an anti-vimentin
antibody, and most of them by an alpha-smooth-muscle-actin antibody, revealing
the presence of fibroblasts and myofibroblasts. BrdU incorporation tests showed
that proliferation of cultured human stromal cells, stimulated by fetal calf
serum, by basic fibroblast growth factor and by epidermal growth factor, was dose
dependently inhibited by PA extract (5-100 microg/mL). Except at 100 microg/mL,
no acute cytotoxicity of the extract was detected after 24 h of culture.
Similarly, the extract dose-dependently inhibited the proliferation of Madin
Darby canine kidney epithelial cells, but to a lesser extent; whatever the dose
of extract, no acute toxicity was evident on this cell line. CONCLUSION: PA
extract inhibits the proliferation of cultured human prostatic myofibroblasts and
fibroblasts. We propose that cultured human prostatic cells offer a reliable
model for preclinical screening of therapeutic agents, and to study the
mechanisms underlying the inhibition of proliferation.
PMID- 17034613
TI - Effects of ovariectomy and oestrogen replacement on the function and expression
of Rho-kinase in rat bladder smooth muscle.
AB - OBJECTIVE: To investigate the effects of ovariectomy and oestrogen replacement on
the function and expression of Rho-kinase in rat bladder smooth muscle, as the
actual effects of oestrogen deprivation on bladder smooth muscle are unclear.
MATERIALS AND METHODS: Female Sprague-Dawley rats were placed into one of three
groups: sham-operated, bilateral ovariectomy-only, and bilateral ovariectomy plus
oestrogen replacement groups. In the last group, oestrogen was replaced by weekly
injection of beta-estradiol 17-cypionate (250 microg/kg subcutaneously for 6
weeks) beginning at 1 week after ovariectomy, whereas the other groups received
vehicle-only injections for 6 weeks. After treatment, the bladder was removed for
muscle strip studies to evaluate the effects of Y-27632, a specific inhibitor of
Rho-kinase, on baseline tension and carbachol-induced tonic contractions. Also,
the protein expression of RhoA and Rho-kinase isoenzymes was assessed by Western
blot analysis. RESULTS: Of the three groups, incubation with 10 microm Y-27632
resulted in the largest decrease in baseline tension of strips from the bilateral
ovariectomy-only group, but this was not statistically significant (P > 0.05).
For carbachol-induced tonic contractions, strips from the bilateral ovariectomy
only group were attenuated the most among the three groups after adding Y-27632
(P < 0.05). However, there were no significant differences in the levels of RhoA
and the two Rho-kinase isoenzymes in bladder tissues from the three groups.
CONCLUSION: Our data show that oestrogen might inhibit the function of Rho-kinase
in bladder smooth muscle, while having no significant effect on its expression.
This finding might help to explain the greater incidence of urinary tract
symptoms suggestive of overactive bladder after the menopause in women.
PMID- 17034614
TI - Have the wheels come off the Asian-Pacific revolution?
PMID- 17034615
TI - Laparoscopic live-donor nephrectomy.
PMID- 17034616
TI - Using routine data to define clinical case-mix and compare hospital outcomes in
urology.
PMID- 17034617
TI - BJU international is really international.
PMID- 17034618
TI - Idiopathic retroperitoneal fibrosis: the case for nonsurgical treatment.
PMID- 17034619
TI - Nurse-led flexible cystoscopy: experience from one UK centre.
PMID- 17034620
TI - Hypoandrogen-metabolic syndrome: a significant issue for men's health.
PMID- 17034621
TI - Surgical atlas. A continent cutaneous ileal neobladder using the serous-lined
extramural valves.
PMID- 17034622
TI - N-terminal region of Saccharomyces cerevisiae eRF3 is essential for the
functioning of the eRF1/eRF3 complex beyond translation termination.
AB - BACKGROUND: Termination of translation in eukaryotes requires two release
factors, eRF1, which recognizes all three nonsense codons and facilitates release
of the nascent polypeptide chain, and eRF3 stimulating translation termination in
a GTP-depended manner. eRF3 from different organisms possess a highly
conservative C region (eRF3C), which is responsible for the function in
translation termination, and almost always contain the N-terminal extension,
which is inessential and vary both in structure and length. In the yeast
Saccharomyces cerevisiae the N-terminal region of eRF3 is responsible for
conversion of this protein into the aggregated and functionally inactive prion
form. RESULTS: Here, we examined functional importance of the N-terminal region
of a non-prion form of yeast eRF3. The screen for mutations which are lethal in
combination with the SUP35-C allele encoding eRF3C revealed the sup45 mutations
which alter the N-terminal domain of eRF1 and increase nonsense codon
readthrough. However, further analysis showed that synthetic lethality was not
caused by the increased levels of nonsense codon readthrough. Dominant mutations
in SUP35-C were obtained and characterized, which remove its synthetic lethality
with the identified sup45 mutations, thus indicating that synthetic lethality was
not due to a disruption of interaction with proteins that bind to this eRF3
region. CONCLUSION: These and other data demonstrate that the N-terminal region
of eRF3 is involved both in modulation of the efficiency of translation
termination and functioning of the eRF1/eRF3 complex outside of translation
termination.
PMID- 17034623
TI - A relationship between oxytocin and anxiety of romantic attachment.
AB - The formation of social bonding is fundamental for several animals, including
humans, for its relevant and obvious impact upon reproduction and, thus, survival
of the species. Recent data would suggest that oxytocin might be one of the
mediators of this process. Given the paucity of data on the possible involvement
of oxytocin in human attachment, the present study was aimed to explore the
possible relationships between the plasma levels of this neuropeptide and
romantic attachment in healthy subjects. Forty-five healthy subjects who
volunteered for the study, were included in the study. The romantic attachment
was assessed using the Italian version of the so-called "Experiences in Close
Relationships" (ECR), a self-report questionnaire for measuring this parameter in
adults. The results showed that attachment anxiety and oxytocin are positively
linked in romantic attachment to a statistically significant degree (r = 0.30, p
= 0.04), that is, the higher the oxytocin levels the higher the score on the
anxiety scale of the ECR. The authors suggest the hypothesis that this link
represents one of the biological processes resulting in those rewarding emotions
related to romantic attachment.
PMID- 17034624
TI - Determination of the genetic structure of remnant Morus boninensis Koidz. trees
to establish a conservation program on the Bonin Islands, Japan.
AB - BACKGROUND: Morus boninensis, is an endemic plant of the Bonin (Ogasawara)
Islands of Japan and is categorized as "critically endangered" in the Japanese
red data book. However, little information is available about its ecological,
evolutionary and genetic status, despite the urgent need for guidelines for the
conservation of the species. Therefore, we adopted Moritz's MU concept, based on
the species' current genetic structure, to define management units and to select
mother tree candidates for seed orchards. RESULTS: Nearly all individuals of the
species were genotyped on the basis of seven microsatellite markers. Genetic
diversity levels in putative natural populations were higher than in putative man
made populations with the exception of those on Otouto-jima Island. This is
because a limited number of maternal trees are likely to have been used for seed
collection to establish the man-made populations. A model-based clustering
analysis clearly distinguished individuals into nine clusters, with a large
difference in genetic composition between the population on Otouto-jima Island,
the putative natural populations and the putative man-made populations. The
Otouto-jima population appeared to be genetically differentiated from the others;
a finding that was also supported by pairwise FST and RST analysis. Although
multiple clusters were detected in the putative man-made populations, the pattern
of genetic diversity was monotonous in comparison to the natural populations.
CONCLUSION: The genotyping by microsatellite markers revealed strong genetic
structures. Typically, artificial propagation of this species has ignored the
genetic structure, relying only on seeds from Otouto-jima for replanting on other
islands, because of a problem with inter-specific hybridization on Chichi-jima
and Haha-jima Islands. However, this study demonstrates that we should be taking
into consideration the genetic structure of the species when designing a
propagation program for the conservation of this species.
PMID- 17034625
TI - Cross-sectional survey of older peoples' views related to influenza vaccine
uptake.
AB - BACKGROUND: The population's views concerning influenza vaccine are important in
maintaining high uptake of a vaccine that is required yearly to be effective.
Little is also known about the views of the more vulnerable older population over
the age of 74 years. METHODS: A cross-sectional survey of community dwelling
people aged 75 years and over wh, previous participant was conducted using a
postal questionnaire. Responses were analysed by vaccine uptake records and by
socio-demographic and medical factors. RESULTS: 85% of men and 75% of women were
vaccinated against influenza in the previous year. Over 80% reported being
influenced by a recommendation by a health care worker. The most common reason
reported for non uptake was good health (44%), or illness considered to be due to
the vaccine (25%). An exploration of the crude associations with socio-economic
status suggested there may be some differences in the population with these two
main reasons. 81% of people reporting good health lived in owner occupied housing
with central heating vs. 63% who did not state this as a reason (p = 0.04),
whereas people reporting ill health due to the vaccine was associated with poorer
social circumstances. 11% lived in the least deprived neighbourhood compared to
36% who did not state this as a reason (p = 0.05) and were less likely to be
currently married than those who did not state this as a reason (25% vs 48% p =
0.05). CONCLUSION: Vaccine uptake was high, but non uptake was still noted in 1
in 4 women and 1 in 7 men aged over 74 years. Around 70% reported they would not
have the vaccine in the following year. The divergent reasons for non-uptake, and
the positive influence from a health care worker, suggests further uptake will
require education and encouragement from a health care worker tailored towards
the different views for not having influenza vaccination. Non-uptake of influenza
vaccine because people viewed themselves as in good health may explain the modest
socio-economic differentials in influenza vaccine uptake in elderly people noted
elsewhere. Reporting of ill-health due to the vaccine may be associated with a
different, poorer background.
PMID- 17034626
TI - Functional dissection of the Drosophila Kallmann's syndrome protein DmKal-1.
AB - BACKGROUND: Anosmin-1, the protein implicated in the X-linked Kallmann's
syndrome, plays a role in axon outgrowth and branching but also in epithelial
morphogenesis. The molecular mechanism of its action is, however, widely unknown.
Anosmin-1 is an extracellular protein which contains a cysteine-rich region, a
whey acidic protein (WAP) domain homologous to some serine protease inhibitors,
and four fibronectin-like type III (FnIII) repeats. Drosophila melanogaster Kal-1
(DmKal-1) has the same protein structure with minor differences, the most
important of which is the presence of only two FnIII repeats and a C-terminal
region showing a low similarity with the third and the fourth human FnIII
repeats. We present a structure-function analysis of the different DmKal-1
domains, including a predicted heparan-sulfate binding site. RESULTS: This study
was performed overexpressing wild type DmKal-1 and a series of deletion and point
mutation proteins in two different tissues: the cephalopharyngeal skeleton of the
embryo and the wing disc. The overexpression of DmKal-1 in the cephalopharyngeal
skeleton induced dosage-sensitive structural defects, and we used these
phenotypes to perform a structure-function dissection of the protein domains. The
reproduction of two deletions found in Kallmann's Syndrome patients determined a
complete loss of function, whereas point mutations induced only minor alterations
in the activity of the protein. Overexpression of the mutant proteins in the wing
disc reveals that the functional relevance of the different DmKal-1 domains is
dependent on the extracellular context. CONCLUSION: We suggest that the role
played by the various protein domains differs in different extracellular
contexts. This might explain why the same mutation analyzed in different tissues
or in different cell culture lines often gives opposite phenotypes. These
analyses also suggest that the FnIII repeats have a main and specific role, while
the WAP domain might have only a modulator role, strictly connected to that of
the fibronectins.
PMID- 17034627
TI - Tumour risk associated with use of cellular telephones or cordless desktop
telephones.
AB - BACKGROUND: The use of cellular and cordless telephones has increased
dramatically during the last decade. There is concern of health problems such as
malignant diseases due to microwave exposure during the use of these devices. The
brain is the main target organ. METHODS: Since the second part of the 1990's we
have performed six case-control studies on this topic encompassing use of both
cellular and cordless phones as well as other exposures. Three of the studies
concerned brain tumours, one salivary gland tumours, one non-Hodgkin lymphoma
(NHL) and one testicular cancer. Exposure was assessed by self-administered
questionnaires. RESULTS: Regarding acoustic neuroma analogue cellular phones
yielded odds ratio (OR) = 2.9, 95 % confidence interval (CI) = 2.0-4.3, digital
cellular phones OR = 1.5, 95 % CI = 1.1-2.1 and cordless phones OR = 1.5, 95 % CI
= 1.04-2.0. The corresponding results were for astrocytoma grade III-IV OR = 1.7,
95 % CI = 1.3-2.3; OR = 1.5, 95 % CI = 1.2-1.9 and OR = 1.5, 95 % CI = 1.1-1.9,
respectively. The ORs increased with latency period with highest estimates using
> 10 years time period from first use of these phone types. Lower ORs were
calculated for astrocytoma grade I-II. No association was found with salivary
gland tumours, NHL or testicular cancer although an association with NHL of T
cell type could not be ruled out. CONCLUSION: We found for all studied phone
types an increased risk for brain tumours, mainly acoustic neuroma and malignant
brain tumours. OR increased with latency period, especially for astrocytoma grade
III-IV. No consistent pattern of an increased risk was found for salivary gland
tumours, NHL, or testicular cancer.
PMID- 17034628
TI - Understanding and meeting the needs of those using growth hormone injection
devices.
AB - BACKGROUND: Recombinant human growth hormone (r-hGH) is used to treat: growth
hormone deficiency in children and adults; children born small for gestational
age; Turner's syndrome; and chronic renal failure. r-hGH is administered by daily
subcutaneous injection and may be given using a number of different
administration devices. The aim of this survey was, firstly, to identify which
attributes of an r-hGH administration device are considered most important to
physicians, teenage patients, parents of young children requiring GH and nurses
who have experience of r-hGH administration, and, secondly, to determine how they
rate existing devices in each of these key attributes. METHODS: The opinions of
67 individuals with experience in r-hGH administration were captured in
discussion sessions. Parents, physicians and nurses were asked to rate 19 device
attributes by completing a questionnaire, and to rank four different r-hGH
administration devices (including a conceptual electronic device) in order of
preference. RESULTS: Reliability, ease of use, lack of pain during injection,
safety in use, storage, and number of steps in preparation before use, during use
and after were considered to be the five most desirable attributes of an r-hGH
administration device. An electronic device was preferred to an automatic, multi
dose injection device, a needle-free injection device or a manual, ready-to-use,
disposable injection device. CONCLUSION: In the opinion of physicians, nurses and
parents using r-hGH injection devices, an ideal device must combine reliability
with simplicity, while delivering treatment with minimal pain. An electronic
device, which combines many of the most useful features of existing devices with
novel functions, was the preferred option for r-hGH administration.
PMID- 17034629
TI - Langerhans cell histiocytosis on the penis: a case report.
AB - BACKGROUND: Langerhans cell histiocytosis affects mainly young children and
features an accumulation of CD1a+ dendritic Langerhans cells in the bone, skin,
and other organs. A few cases of Langerhans cell histiocytosis on the penis have
been reported in the literature. We present a case of Langerhans cell
histiocytosis on the penis and review the similar cases in the literature. CASE
PRESENTATION: The patient was a 13-year-old boy who had a history of lymph node,
femur bone, and pituitary-thalmic axis lesions from Langerhans cell histiocytosis
who noticed a painful nodule on the prepuce of his penis. The histological and
immunohistochemical examination fulfilled the criteria of Langerhans cell
histiocytosis. CONCLUSION: We herein describe the case reported of Langerhans
cell histiocytosis on the penis.
PMID- 17034630
TI - Bilateral ischemic optic neuropathy after transurethral prostatic resection: a
case report.
AB - BACKGROUND: Nonarteritic ischemic optic neuropathy affects the anterior portion
of the optic nerve and is characterized by sudden, painless visual loss. The
affected eye has a relative afferent pupillary defect. The typical funduscopic
appearance includes optic disc edema, with associated nerve fiber layer
hemorrhage. Risk factors include advanced age, systemic hypertension, nocturnal
hypotension, diabetes mellitus, and a small cup-to-disc ratio. Bilateral
presentation is rare. Postoperative optic neuropathy has been associated with
nonocular surgery; risk factors include a combination of prolonged surgical
times, acute systemic hypotension, anemia due to blood loss, or prone
positioning. We report for the first time a patient with bilateral, simultaneous
anterior ischemic optic neuropathy after elective transurethral prostatic
resection. CASE PRESENTATION: A 66-year old man underwent surgery for benign
prostatic hyperplasia. The preoperative blood pressure was 140/85 mmHg,
hemoglobin 15.9 g/dL, and hematocrit 48.6%. Two hours postoperatively, the blood
pressure, hemoglobin, and hematocrit dropped dramatically. One day later,
transient horizontal diplopia developed. Funduscopy showed a congenitally small
cup-to-disc ratio without papillary edema. Other ocular findings were
unremarkable. By 4 days postoperatively, sudden and painless amaurosis
bilaterally developed when the patient awoke with nausea and vomiting. Visual
acuity was no light perception bilaterally. The optic discs were swollen with
small hemorrhages. Scans of the head and orbits and electrolyte levels were
normal. There were no responses on visual evoked potentials bilaterally. The
blood pressure was 90/50 mm Hg, the hemoglobin 7.0 g/dL, and the hematocrit
22.9%, necessitating infusion of three units of packed red blood cells. The blood
pressure, hematocrit, and hemoglobin increased to normal levels. Three months
later the visual acuity remained no light perception. The pupils were unreactive
and there was marked optic disc atrophy bilaterally. CONCLUSION: Bilateral and
simultaneous acute ischemic optic neuropathy may be a rare but devastating
surgical complication. The combination of anemia and hypotension may increase the
risk of anterior ischemic optic neuropathy postoperatively after transurethral
prostatic resection.
PMID- 17034631
TI - Spontaneous intra-peritoneal bleeding secondary to warfarin, presenting as an
acute appendicitis: a case report and review of literature.
AB - BACKGROUND: Warfarin is a coumarin anti-coagulant, used widely for the
therapeutic and prophylactic anticoagulation. Although, it is considered as a
life saving medicine, it is associated with the significant adverse effects
including intra-abdominal bleeding, which have been very well documented in
literature. However, the presentation of warfarin induced intra-peritoneal
bleeding as an acute appendicitis has not been reported in English literature. We
report this rare, spontaneous intra-peritoneal bleeding secondary to warfarin
therapy, mimicking the signs and symptoms of an acute appendicitis for the first
time in English literature. CASE PRESENTATION: A 41 year-old female patient who
was on warfarin for prophylaxis following the previous episode of pulmonary
embolism, presented to the Casualty with the typical symptoms of an acute
appendicitis. During operative intervention, we found it to be the spontaneous
intra-peritoneal bleeding secondary to warfarin. The patient recovered well
following the operation. CONCLUSION: We recommend the use of the radiological
investigations in all the cases of acute abdomen who are on warfarin even if the
INR is within the therapeutic range.
PMID- 17034633
TI - Guidance for industry: patient-reported outcome measures: use in medical product
development to support labeling claims: draft guidance.
AB - This guidance describes how the FDA evaluates patient-reported outcome (PRO)
instruments used as effectiveness endpoints in clinical trials. It also describes
our current thinking on how sponsors can develop and use study results measured
by PRO instruments to support claims in approved product labeling (see appendix
point 1). It does not address the use of PRO instruments for purposes beyond
evaluation of claims made about a drug or medical product in its labeling. By
explicitly addressing the review issues identified in this guidance, sponsors can
increase the efficiency of their endpoint discussions with the FDA during the
product development process, streamline the FDA's review of PRO endpoint
adequacy, and provide optimal information about the patient's perspective of
treatment benefit at the time of product approval. A PRO is a measurement of any
aspect of a patient's health status that comes directly from the patient (i.e.,
without the interpretation of the patient's responses by a physician or anyone
else). In clinical trials, a PRO instrument can be used to measure the impact of
an intervention on one or more aspects of patients' health status, hereafter
referred to as PRO concepts, ranging from the purely symptomatic (response of a
headache) to more complex concepts (e.g., ability to carry out activities of
daily living), to extremely complex concepts such as quality of life, which is
widely understood to be a multidomain concept with physical, psychological, and
social components. Data generated by a PRO instrument can provide evidence of a
treatment benefit from the patient perspective. For this data to be meaningful,
however, there should be evidence that the PRO instrument effectively measures
the particular concept that is studied. Generally, findings measured by PRO
instruments may be used to support claims in approved product labeling if the
claims are derived from adequate and well-controlled investigations that use PRO
instruments that reliably and validly measure the specific concepts at issue. The
glossary defines many of the terms used in this guidance. In particular, the term
instrument refers to the actual questions or items contained in a questionnaire
or interview schedule along with all the additional information and documentation
that supports the use of these items in producing a PRO measure (e.g.,
interviewer training and instructions, scoring and interpretation manual). The
term conceptual framework refers to how items are grouped according to
subconcepts or domains (e.g., the item walking without help may be grouped with
another item, walking with difficulty, within the domain of ambulation, and
ambulation may be further grouped into the concept of physical ability). FDA's
guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidance documents describe the Agency's current
thinking on a topic and should be viewed only as recommendations, unless specific
regulatory or statutory requirements are cited. The use of the word should in
Agency guidance documents means that something is suggested or recommended but
not required. First publication of the Draft Guidance by the Food and Drug
Administration--February 2006.
PMID- 17034634
TI - Simultaneous alcohol and cannabis expectancies predict simultaneous use.
AB - BACKGROUND: Simultaneous use of alcohol and cannabis predicts increased negative
consequences for users beyond individual or even concurrent use of the two drugs.
Given the widespread use of the drugs and common simultaneous consumption,
problems unique to simultaneous use may bear important implications for many
substance users. Cognitive expectancies offer a template for future drug use
behavior based on previous drug experiences, accurately predicting future use and
problems. Studies reveal similar mechanisms underlying both alcohol and cannabis
expectancies, but little research examines simultaneous expectancies for alcohol
and cannabis use. Whereas research has demonstrated unique outcomes associated
with simultaneous alcohol and cannabis use, this study hypothesized that unique
cognitive expectancies may underlie simultaneous alcohol and cannabis use.
RESULTS: This study examined a sample of 2600 (66% male; 34% female) Internet
survey respondents solicited through advertisements with online cannabis-related
organizations. The study employed known measures of drug use and expectancies, as
well as a new measure of simultaneous drug use expectancies. Expectancies for
simultaneous use of alcohol and cannabis predicted simultaneous use over and
above expectancies for each drug individually. DISCUSSION: Simultaneous
expectancies may provide meaningful information not available with individual
drug expectancies. These findings bear potential implications on the assessment
and treatment of substance abuse problems, as well as researcher
conceptualizations of drug expectancies. Policies directing the treatment of
substance abuse and its funding ought to give unique consideration to
simultaneous drug use and its cognitive underlying factors.
PMID- 17034632
TI - Acute ischemic heart disease and interventional cardiology: a time for pause.
AB - BACKGROUND: A major change has occurred in the last few years in the therapeutic
approach to patients presenting with all forms of acute coronary syndromes.
Whether or not these patients present initially to tertiary cardiac care centers,
they are now routinely referred for early coronary angiography and increasingly
undergo percutaneous revascularization. This practice is driven primarily by the
angiographic image and technical feasibility. Concomitantly, there has been a
decline in expectant or ischemia-guided medical management based on specific
clinical presentation, response to initial treatment, and results of noninvasive
stratification. This 'tertiarization' of acute coronary care has been fueled by
the increasing sophistication of the cardiac armamentarium, the peer-reviewed
publication of clinical studies purporting to show the superiority of invasive
cardiac interventions, and predominantly supporting (non-peer-reviewed)
editorials, newsletters, and opinion pieces. DISCUSSION: This review presents
another perspective, based on a critical reexamination of the evidence. The
topics addressed are: reperfusion treatment of ST-elevation myocardial
infarction; the indications for invasive intervention following thrombolysis; the
role of invasive management in non-ST-elevation myocardial infarction and
unstable angina; and cost-effectiveness and real world considerations. A few
cases encountered in recent practice in community and tertiary hospitals are
presented for illustrative purposes The numerous and far-reaching scientific,
economic, and philosophical implications that are a consequence of this marked
change in clinical practice as well as healthcare, decisional and conflict of
interest issues are explored. SUMMARY: The weight of evidence does not support
the contemporary unfocused broad use of invasive interventional procedures across
the spectrum of acute coronary clinical presentations. Excessive and unselective
recourse to these procedures has deleterious implications for the organization of
cardiac health care and undesirable economic, scientific and intellectual
consequences. It is suggested that there is need for a new equilibrium based on
more refined clinical risk stratification in the treatment of patients who
present with acute coronary syndromes.
PMID- 17034635
TI - A web-based system for tissue microarray data management.
AB - BACKGROUND: Tissue Microarray is a novel technique for analysing large amounts of
immunohistochemically stained specimens. However, those large amounts make it
difficult to design, prepare and analyze a tissue microarray, so that software
support is almost inevitable. METHODS: We designed a tissue microarray data
management system starting from specifications obtained by pathologists, and
arranged for a preliminary validation in thyroid pathology. RESULTS: A web-based
system has been developed, basing on open-source software and principles, that
was well accepted by pathologists and allowed to carry out a study on 52 thyroid
pathology cases. CONCLUSION: Though limited in functionalities, the developed
system is effective and can be downloaded at the address
http://mitel.dimi.uniud.it/timan/.
PMID- 17034636
TI - Harm reduction services for British Columbia's First Nation population: a
qualitative inquiry into opportunities and barriers for injection drug users.
AB - BACKGROUND: Aboriginal injection drug users are the fastest growing group of new
Human Immunodeficiency Virus cases in Canada. However, there remains a lack of
comprehensive harm reduction services available to First Nation persons,
particularly for First Nation people dwelling in rural and reserve communities.
This paper reports findings from an exploratory study of current harm reduction
practices in First Nation communities. The purpose of this study was to provide
an overview of the availability and content of current harm reduction practices,
as well as to identify barriers and opportunities for implementing these services
in First Nation communities. METHODS: Key informant interviews were conducted
with 13 addictions service providers from the province of British Columbia,
Canada. RESULTS: Participants identified barriers to these services such as
community size and limited service infrastructure, lack of financial resources,
attitudes towards harm reduction services and cultural differences. CONCLUSION:
It was recommended that community education efforts be directed broadly within
the community before establishing harm reduction services and that the readiness
of communities be assessed.
PMID- 17034637
TI - Dynamics of immune response and drug resistance in malaria infection.
AB - BACKGROUND: Malaria parasites that concurrently infect a host compete on the
basis of their intrinsic growth rates and by stimulating cross-reactive immune
responses that inhibit each others' growth. If the phenotypes also show different
drug sensitivities ('sensitive' vs. 'resistant' strains), drug treatment can
change their joint dynamics and the long-term outcome of the infection: most
obviously, persistent drug pressure can permit the more resistant, but otherwise
competitively-inferior, strains to dominate. METHODS: Here a mathematical model
is developed to analyse how these and more subtle effects of antimalarial drug
use are modulated by immune response, repeated re-inoculation of parasites, drug
pharmacokinetic parameters, dose and treatment frequency. RESULTS: The model
quantifies possible effects of single and multiple (periodic) treatment on the
outcome of parasite competition. In the absence of further inoculation, the
dosage and/or treatment frequency required for complete clearance can be
estimated. With persistent superinfection, time-average parasite densities can be
derived in terms of the basic immune-regulating parameters, the drug efficacy and
treatment regimen. CONCLUSION: The functional relations in the model are
applicable to a wide range of conditions and transmission environments, allowing
predictions to be made on both the individual and the community levels, and, in
particular, transitions from drug-sensitive to drug-resistant parasite dominance
to be projected on both levels.
PMID- 17034638
TI - An overabundance of phase 0 introns immediately after the start codon in
eukaryotic genes.
AB - BACKGROUND: A knowledge of the positions of introns in eukaryotic genes is
important for understanding the evolution of introns. Despite this, there has
been relatively little focus on the distribution of intron positions in genes.
RESULTS: In proteins with signal peptides, there is an overabundance of phase 1
introns around the region of the signal peptide cleavage site. This has been
described before. But in proteins without signal peptides, a novel phenomenon is
observed: There is a sharp peak of phase 0 intron positions immediately following
the start codon, i.e. between codons 1 and 2. This effect is seen in a wide range
of eukaryotes: Vertebrates, arthropods, fungi, and flowering plants. Proteins
carrying this start codon intron are found to comprise a special class of
relatively short, lysine-rich and conserved proteins with an overrepresentation
of ribosomal proteins. In addition, there is a peak of phase 0 introns at
position 5 in Drosophila genes with signal peptides, predominantly representing
cuticle proteins. CONCLUSION: There is an overabundance of phase 0 introns
immediately after the start codon in eukaryotic genes, which has been described
before only for human ribosomal proteins. We give a detailed description of these
start codon introns and the proteins that contain them.
PMID- 17034639
TI - Role of TNFalpha in pulmonary pathophysiology.
AB - Tumor necrosis factor alpha (TNFalpha) is the most widely studied pleiotropic
cytokine of the TNF superfamily. In pathophysiological conditions, generation of
TNFalpha at high levels leads to the development of inflammatory responses that
are hallmarks of many diseases. Of the various pulmonary diseases, TNFalpha is
implicated in asthma, chronic bronchitis (CB), chronic obstructive pulmonary
disease (COPD), acute lung injury (ALI) and acute respiratory distress syndrome
(ARDS). In addition to its underlying role in the inflammatory events, there is
increasing evidence for involvement of TNFalpha in the cytotoxicity. Thus,
pharmacological agents that can either suppress the production of TNFalpha or
block its biological actions may have potential therapeutic value against a wide
variety of diseases. Despite some immunological side effects, anti-TNFalpha
therapeutic strategies represent an important breakthrough in the treatment of
inflammatory diseases and may have a role in pulmonary diseases characterized by
inflammation and cell death.
PMID- 17034640
TI - Patient-reported outcomes in a trial of exenatide and insulin glargine for the
treatment of type 2 diabetes.
AB - BACKGROUND: Patient-reported measures can be used to examine whether drug
differences other than clinical efficacy have an impact on outcomes that may be
important to patients. Although exenatide and insulin glargine appear to have
similar efficacy for treatment of type 2 diabetes, there are several differences
between the two treatments that could influence outcomes from the patient's
perspective. The purpose of the current study was to examine whether the two
drugs were comparable as assessed by patient-reported outcomes using data from a
clinical trial in which these injectable medications were added to pre-existing
oral treatment regimens. METHODS: Patients were randomized to either twice daily
exenatide or once daily insulin glargine during a 26-week international trial. At
baseline and endpoint, five patient-reported outcome measures were administered:
the Vitality Scale of the SF-36, The Diabetes Symptom Checklist - Revised (DSC
R), the EuroQol EQ-5D, the Treatment Flexibility Scale (TFS), and the Diabetes
Treatment Satisfaction Questionnaire (DTSQ). Change from baseline to endpoint was
analyzed within each treatment group. Group differences were examined with
General linear models (GLMs), controlling for country and baseline scores.
RESULTS: A total of 549 patients with type 2 diabetes were enrolled in the trial,
and current analyses were conducted with data from the 455 per protocol patients
(228 exenatide and 227 insulin glargine). The sample was primarily Caucasian
(79.6%), with slightly more men (55.2%) than women, and with a mean age of 58.5
years. Paired t-tests found that both treatment groups demonstrated statistically
significant baseline to endpoint change on several of the health outcomes
instruments including the DSC-R, DTSQ, and the SF-36 Vitality subscale. GLMs
found no statistically significant differences between groups in change on the
health outcomes instruments. CONCLUSION: This analysis found that both exenatide
and insulin glargine were associated with significant improvements in patient
reported outcomes when added to oral medications among patients with type 2
diabetes. Despite an additional daily injection and a higher rate of
gastrointestinal adverse events, treatment satisfaction in the exenatide group
was comparable to that of the glargine group, possibly because of weight
reduction observed in patients treated with exenatide.
PMID- 17034641
TI - Development of a Health-Related Quality of Life Questionnaire (HRQL) for patients
with Extremity Soft Tissue Infections (ESTI).
AB - BACKGROUND: Past clinical trials of antimicrobial treatment in soft tissue
infections have focused on non-standardized clinical and physiological outcome
variables, and have not considered the subjective experience of patients. The
objective of this study was to develop a health-related quality of life
questionnaire (HRQL) for patients with extremity soft tissue infections (ESTI)
for future use in clinical trials. METHODS: The design of this study followed
published guidelines and included item generation, item reduction, and
questionnaire preparation. Study subjects were consenting English-speaking adults
with acute ESTI requiring prescription of at least two days of outpatient
intravenous antibiotic therapy. RESULTS: A list of 49 items that adversely impact
the quality of life of patients with ESTI was generated by literature review,
informal health professional feedback, and semi-structured interviews with twenty
patients. A listing of these items was then administered to 95 patients to
determine their relative importance on quality of life. A questionnaire was
prepared that included the twenty most important items with a 5-point Likert
scale response. Questionnaire domains included physical symptoms, problems
performing their activities of daily living, impairment of their emotional
functioning, and difficulties in their social interactions as related to their
ESTI. The final questionnaire was pre-tested on a further ten patients and was
named the ESTI-Score. CONCLUSION: The ESTI-Score is a novel instrument designed
to quantify the impact of ESTI on quality of life. Future study is required to
determine its validity and responsiveness before use as an outcome measure in
clinical trials.
PMID- 17034642
TI - Identification of biomolecule mass transport and binding rate parameters in
living cells by inverse modeling.
AB - BACKGROUND: Quantification of in-vivo biomolecule mass transport and reaction
rate parameters from experimental data obtained by Fluorescence Recovery after
Photobleaching (FRAP) is becoming more important. METHODS AND RESULTS: The
Osborne-More extended version of the Levenberg-Marquardt optimization algorithm
was coupled with the experimental data obtained by the Fluorescence Recovery
after Photobleaching (FRAP) protocol, and the numerical solution of a set of two
partial differential equations governing macromolecule mass transport and
reaction in living cells, to inversely estimate optimized values of the molecular
diffusion coefficient and binding rate parameters of GFP-tagged glucocorticoid
receptor. The results indicate that the FRAP protocol provides enough information
to estimate one parameter uniquely using a nonlinear optimization technique.
Coupling FRAP experimental data with the inverse modeling strategy, one can also
uniquely estimate the individual values of the binding rate coefficients if the
molecular diffusion coefficient is known. One can also simultaneously estimate
the dissociation rate parameter and molecular diffusion coefficient given the
pseudo-association rate parameter is known. However, the protocol provides
insufficient information for unique simultaneous estimation of three parameters
(diffusion coefficient and binding rate parameters) owing to the high
intercorrelation between the molecular diffusion coefficient and pseudo
association rate parameter. Attempts to estimate macromolecule mass transport and
binding rate parameters simultaneously from FRAP data result in misleading
conclusions regarding concentrations of free macromolecule and bound complex
inside the cell, average binding time per vacant site, average time for diffusion
of macromolecules from one site to the next, and slow or rapid mobility of
biomolecules in cells. CONCLUSION: To obtain unique values for molecular
diffusion coefficient and binding rate parameters from FRAP data, we propose
conducting two FRAP experiments on the same class of macromolecule and cell. One
experiment should be used to measure the molecular diffusion coefficient
independently of binding in an effective diffusion regime and the other should be
conducted in a reaction dominant or reaction-diffusion regime to quantify binding
rate parameters. The method described in this paper is likely to be widely used
to estimate in-vivo biomolecule mass transport and binding rate parameters.
PMID- 17034643
TI - Signal stability of Cy3 and Cy5 on antibody microarrays.
AB - BACKGROUND: The antibody microarray technique is a newly emerging proteomics tool
for differential protein expression analyses that uses fluorescent dyes Cy 3 and
Cy 5. Environmental factors, such as light exposure, can affect the signal
intensity of fluorescent dyes on microarray slides thus, it is logical to scan
microarray slides immediately after the final wash and drying processes. However,
no research data are available concerning time-dependent changes of fluorescent
signals on antibody microarray slides to this date. In the present study,
microarray slides were preserved at -20 degrees C after regular microarray
experiments and were rescanned at day 10, 20 and 30 to evaluate change in signal
intensity. RESULTS: Fluorescent intensities of microarray spots were detected
using a confocal laser scanner after the experiment at day 0, and re-examined at
day 10, 20 and 30, respectively. Fluorescent intensities of rescanned microarray
spots did not show significant changes when compared with those scanned
immediately after standard microarray experiments. CONCLUSION: Microarray slides
can be preserved and rescanned multiple times using a confocal laser scanner over
a period of days or weeks.
PMID- 17034644
TI - In vitro activity effects of combinations of cephalothin, dicloxacillin,
imipenem, vancomycin and amikacin against methicillin-resistant Staphylococcus
spp. strains.
AB - BACKGROUND: combinations of drugs has been proposed as an alternative for
oxacillin-resistant staphylococci infections, however, limited information about
in vitro combinations are available for multi-resistant strains. The objective of
this study was to describe the interaction of beta-lactams in combination with
vancomycin or amikacin against 26 oxacillin and amikacin-resistant nosocomial
Staphylococcus spp. isolates. METHODS: activity of dicloxacillin plus amikacin,
cephalothin plus amikacin, cephalothin plus vancomycin, imipenem plus vancomycin
and vancomycin plus amikacin was evaluated by checkerboard synergy tests and the
fractional inhibitory concentration index (FIC) was calculated. RESULTS:
dicloxacillin plus amikacin, and cephalothin plus amikacin were synergistic or
partially synergistic in 84.6% and 100% respectively. For nearly half of the
isolates the mean concentrations of dicloxacillin, cephalothin and amikacin at
which FIC indexes were calculated were achievable therapeutically. Vancomycin
plus amikacin had synergistic effect only against two isolates, and partially
synergistic in 38.6%. For the combinations vancomycin plus cephalothin and
vancomycin plus imipenem the effect was additive in 76.9% and 80.7% respectively.
CONCLUSION: in this study the checkerboard analysis showed that amikacin in
combination with cephalothin or dicloxacillin was synergistic against most of the
resistant strains of S. aureus and coagulase-negative Staphylococcus. Vancomycin
in combination with a beta-lactam (cephalothin or imipenem) showed additivity. An
indifferent effect predominated for the combination vancomycin plus amikacin.
Even though a synergistic effect is expected when using a beta-lactam plus
amikacin combination, it is possible that the effect cannot be clinically
achievable. Careful selection of antimicrobial combinations and initial MICs are
mandatory for future evaluations.
PMID- 17034645
TI - Factors associated with breastfeeding at six months postpartum in a group of
Australian women.
AB - BACKGROUND: Despite high levels of breastfeeding initiation in Australia, only 47
percent of women are breastfeeding (exclusively or partially) six months later,
with marked differences between social groups. It is important to identify women
who are at increased risk of early cessation of breastfeeding. METHODS: Data from
the three arms of a randomised controlled trial were pooled and analysed as a
cohort using logistic regression to identify which factors predicted women
continuing to feed any breast milk at six months postpartum. The original trial
included 981 primiparous women attending a public, tertiary, women's hospital in
Melbourne, Australia in 1999-2001. The trial evaluated the effect of two mid
pregnancy educational interventions on breastfeeding initiation and duration. In
the 889 women with six month outcomes available, neither intervention increased
breastfeeding initiation nor duration compared to standard care. Independent
variables were included in the predictive model based on the literature and
discussion with peers and were each tested individually against the dependent
variable (any breastfeeding at six months). RESULTS: Thirty-three independent
variables of interest were identified, of which 25 qualified for inclusion in the
preliminary regression model; 764 observations had complete data available.
Factors remaining in the final model that were positively associated with
breastfeeding any breast milk at six months were: a very strong desire to
breastfeed; having been breastfed oneself as a baby; being born in an Asian
country; and older maternal age. There was an increasing association with
increasing age. Factors negatively associated with feeding any breast milk at six
months were: a woman having no intention to breastfeed six months or more;
smoking 20 or more cigarettes per day pre-pregnancy; not attending childbirth
education; maternal obesity; having self-reported depression in the six months
after birth; and the baby receiving infant formula while in hospital. CONCLUSION:
In addition to the factors commonly reported as being associated with
breastfeeding in previous work, this study found a negative association between
breastfeeding outcomes and giving babies infant formula in hospital, a high
maternal body mass index, and self-reported maternal depression or anxiety in the
six months after the baby was born. Interventions that seek to increase
breastfeeding should consider focusing on women who wish to breastfeed but are at
high risk of early discontinuation.
PMID- 17034646
TI - Alveolar proteinosis in a patient recovering from Pneumocystis carinii infection:
a case report with a review of literature.
AB - BACKGROUND: Pulmonary alveolar proteinosis is a rare lung disorder, which was
first reported as idiopathic condition in 1958. The prevalence of acquired
pulmonary alveolar proteinosis has been estimated to be 0.37 per 100,000
population. The cause of this condition is not entirely clear. We present
alveolar proteinosis in a case recently treated for pulmonary Pneumocystis
carinii infection. CASE PRESENTATION: A 25-year-old Caucasian female presented
with shortness of breath during management of acute pancreatitis. She had a heart
transplant six years ago, a distal pancreatectomy secondary to pancreatitis two
years ago, chronic renal failure secondary to Prograft taken for six years to
suppress transplant rejection, and a more recent history of Pneumocystis carinii
infection treated in the preceding 21 days with augmented doses of Bactrim
(Trimethoprim, Sulfamethoxazole). She had bilateral pleural effusions with
radiological and clinical features suspicious for interstitial lung disease.
Cytopathologic evaluation of broncho-alveolar lavage (BAL) showed hyaline
alveolar casts admixed with amorphous debris and scant chronic inflammatory
cells, consistent with alveolar proteinosis. GMS and PAS stains were negative for
P. carinii. Direct Fluorescent Antibody (DFA) test for P. carinii performed on
the BAL specimen in our Microbiology Lab had been repeatedly negative.
CONCLUSION: Cytopathological findings in bronchoalveolar lavage, with clinical
differential diagnosis of interstitial lung disease, were diagnostic. Pulmonary
alveolar proteinosis after recent treatment for P. carinii infection suggests a
relationship of pulmonary alveolar proteinosis with P. carinii infection in the
immunocompromised patient.
PMID- 17034647
TI - 5' long terminal repeat (LTR)-selective methylation of latently infected HIV-1
provirus that is demethylated by reactivation signals.
AB - We previously described selective hypermethylation of the 5'-long terminal repeat
(LTR) of HTLV-1 provirus in vivo and in vitro. This prompted us to analyze CpG
methylation of the two LTRs of the HIV provirus in chronically infected cell
lines. The results demonstrate selective hypermethylation of the 5' LTR of the
HIV provirus in ACH-2 cells. Moreover, induction of viral gene expression by TNF
alpha resulted in demethylation of the 5'-LTR. These results suggest that
selective epigenetic modification of the 5'LTR of the HIV-1 provirus may be an
important mechanism by which proviral activity is suppressed.
PMID- 17034648
TI - Crimean-Congo haemorrhagic fever in Kosova : a fatal case report.
AB - Crimean-Congo haemorrhagic fever (CCHF) is an often fatal viral infection
described in about 30 countries around the world. The authors report a fatal case
of Crimean-Congo hemorrhagic fever (CCHF) observed in a patient from Kosova. The
diagnosis of CCHF was confirmed by reverse transcription-PCR. Late diagnosis
decreased the efficacy of treatment and patient died due to severe complications
of infection.
PMID- 17034649
TI - Creating a medical English-Swedish dictionary using interactive word alignment.
AB - BACKGROUND: This paper reports on a parallel collection of rubrics from the
medical terminology systems ICD-10, ICF, MeSH, NCSP and KSH97-P and its use for
semi-automatic creation of an English-Swedish dictionary of medical terminology.
The methods presented are relevant for many other West European language pairs
than English-Swedish. METHODS: The medical terminology systems were collected in
electronic format in both English and Swedish and the rubrics were extracted in
parallel language pairs. Initially, interactive word alignment was used to create
training data from a sample. Then the training data were utilised in automatic
word alignment in order to generate candidate term pairs. The last step was
manual verification of the term pair candidates. RESULTS: A dictionary of 31,000
verified entries has been created in less than three man weeks, thus with
considerably less time and effort needed compared to a manual approach, and
without compromising quality. As a side effect of our work we found 40 different
translation problems in the terminology systems and these results indicate the
power of the method for finding inconsistencies in terminology translations. We
also report on some factors that may contribute to making the process of
dictionary creation with similar tools even more expedient. Finally, the
contribution is discussed in relation to other ongoing efforts in constructing
medical lexicons for non-English languages. CONCLUSION: In three man weeks we
were able to produce a medical English-Swedish dictionary consisting of 31,000
entries and also found hidden translation errors in the utilized medical
terminology systems.
PMID- 17034650
TI - Studies on cell-cycle synchronization in the asexual erythrocytic stages of
Plasmodium falciparum.
AB - Multiplication of Plasmodium parasites within human erythrocytes is essential to
malarial disease. The cell-division cycle of this organism, however, is still
poorly understood. In other eukaryotes, various techniques for (apparent) cell
cycle synchronization have been used to shed light on the mechanisms involved in
cell division and its control. Thus far there is no technique for cell-cycle
synchronization (as opposed to selection of parasites of a limited age-range) in
Plasmodium. We therefore investigated the possibility that inhibitors of DNA
synthesis, the mitotic spindle, or cell-cycle control elements (such as cyclin
dependent kinases) could be used to synchronize P. falciparum cultures to a
particular cell-cycle phase. Surprisingly, most of these compounds did not cause
a block at a specific phase. Three compounds, Hoechst 33342, roscovitine and L
mimosine, did block development at the trophozoite-schizont transition (S or G2
phase). The block caused by the latter 2 inhibitors was reversible, suggesting
that they might be used as synchronizing agents. However, a consideration of the
perturbing effects of inhibitors and problems with 'batch' synchronization
techniques in general lead us to believe that any results obtained using
roscovitine- or L-mimosine-treated parasites may not be reflective of the normal
cell cycle.
PMID- 17034651
TI - Assessment and prevention of gastrointestinal toxicity of non-steroidal anti
inflammatory drugs.
AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for analgesic,
anti-inflammatory and, in the case of aspirin, for anti-thrombotic actions. The
serious gastrointestinal side-effects associated with these drugs are of concern
and pose a significant obstacle to their use. This review discusses the
pathogenic mechanisms by which the conventional acidic NSAIDs induce
gastrointestinal toxicity, with particular emphasis on non-prostaglandin effects.
Methods of assessment of NSAID-induced enteropathy are reviewed, with particular
emphasis on the use of functional measurement of NSAID-induced changes in the
gastrointestinal tract. The advances in our knowledge of the pathogenesis of
these effects have resulted in the development of a range of novel NSAIDs. Where
functional assessment of the effects of NSAIDs has been employed, it appears to
be more useful as an indicator of early-stage changes rather than a predictor of
the effects of long-term NSAID exposure. Successful pharmaceutical strategies now
offer considerable promise for reducing the severity of NSAID damage to the
gastrointestinal tract. The utility of intestinal permeability measurements for
selection and assessment of these strategies is discussed.
PMID- 17034652
TI - Factorial designed experiment to study the effects of excipients on the
mechanical properties of pellets.
AB - The aim of this work was to determine the effects of formulation factors on the
mechanical properties of pellets produced by the process of extrusion and
spheronisation. A range of properties from a simple fracture load to detailed
load/displacement curves were used to study the effects of the levels of lactose
monohydrate and glyceryl monostearate on the mechanical properties of pellets in
terms of their surface tensile strength, pellet deformability and linear strain.
A series of independent 2(2)-factorial designs were employed to establish the
relationships between composition of the formulations and pellet properties,
whereby the concept of an excess variable was explored. It was found that the
spheronisation aid used, microcrystalline cellulose, is the domineering factor in
most mechanical properties studied, except for the surface tensile strength,
which decreased significantly with an increase in glyceryl monostearate
concentration. The change in binder liquid from water to a water/ethanol mixture
further changed the behaviour of the systems significantly. The assumption of an
excess variable being less critical for the statistical outcome of a factorial
experiment has not been found feasible for the systems studied.
PMID- 17034653
TI - Intranasal midazolam: a comparison of two delivery devices in human volunteers.
AB - Bidirectional nasal drug delivery is a new administration principle with improved
deposition pattern that may increase nasal drug uptake. Twelve healthy subjects
were included in this open, non-randomized 3-way crossover study: midazolam (3.4
mg) intravenously (1 mg mL (-1)), or nasally by bidirectional or traditional
spray (2 x100 microL of a 17 mg mL(-1) nasal midazolam formulation). The primary
outcome was bioavailability. Blood samples were drawn for 6 h for determination
(gas-chromatography-mass-spectrometry) of midazolam and 1-OH-midazolam.
Pharmacokinetic calculations were based on non-compartmental modelling, sedation
assessed by a subjective 0-10 NRS-scale, and nasal dimensions by non-invasive
acoustic rhinometry. Mean bioavailabilities were 0.68-0.71, and Tmax 15 min for
the sprays, which also were bioequivalent (ratio geometric means (90%) CI: 97.6%
(90% CI 83.5; 113.9)). Sedation after bidirectional spray followed intravenous
sedation closely, while sedation after the traditional spray was less pronounced.
A negative correlation between Cmax and smallest cross-sectional area was seen.
Adverse effects such as local irritation did not differ significantly between the
sprays. Apparently bidirectional delivery did not increase systemic
bioavailability of midazolam. We cannot disregard that only the traditional spray
caused less sedation than intravenous administration. This finding needs to be
confirmed in trials designed for this purpose.
PMID- 17034654
TI - Fast-dissolving microparticles fail to show improved oral bioavailability.
AB - Oral dosage forms are the preferred means of delivering drugs for systemic
absorption. However, development problems occur for drugs with poor water
solubility and/or gastrointestinal permeability. It is generally believed that
the in-vivo bioavailability of poorly water-soluble drugs from Class II of the
Biopharmaceutics Classification System can be improved by increasing the
dissolution rate. We have attempted to increase the in-vivo oral bioavailability
of a model Class II drug (griseofulvin) by preparing rapidly-dissolving
particles. The solvent-diffusion method was used to prepare particles with
hydrophilic surfactants (Brij 76/Tween 80 surfactant blend) and in-vivo studies
were conducted in rats. The griseofulvin particles produced were bipyramidal in
habit with a particle size of 2.18 +/- 0.12 microm; they contained crystalline
drug and a relatively large proportion (12% w/w) of hydrophilic surfactant. The
latter and the small particle size ensured rapid particle dispersion and
dissolution in-vitro. Thus, within 30 min of the in-vitro dissolution test, the
bipyramidal particles had released approximately 70% of drug compared with
approximately 10% from the starting material (particle size 12.61 +/- 1.11
microm). However, the rapid and increased drug dissolution in-vitro was not
translated to rapid and enhanced absorption in-vivo, and the oral bioavailability
of the model drug was found to be the same from the control and from the
bipyramidal particles. The poor in-vivo performance of the bipyramidal particles
showed that although the dissolution rate of a Class II drug is thought to be a
good indicator of its in-vivo bioavailability, this is not always the case.
PMID- 17034655
TI - Histological evaluation of buccal penetration enhancement properties of chitosan
and trimethyl chitosan.
AB - The aim of the present work was to compare the penetration enhancement properties
of chitosan hydrochloride (HCS) both as a polymeric solution and as a
nanoparticulate system with that of trimethyl chitosan hydrochloride (TMC) on
buccal mucosa. The hydrophilic high molecular weight fluorescein isothiocyanate
dextran (FD4; 4400 Da) was used as a macromolecule model. The mechanism involved
in the HCS (solution and nanoparticles) and TMC solution penetration enhancement
was investigated on pig buccal mucosa, characterized by having stratified
epithelium and lacking in tight junctions. The permeation/penetration of FD4 and
the change in morphology and histology of the mucosa after contact with the
polymers were assessed: the experiments were performed ex-vivo by applying the
formulations on excised porcine buccal tissue. For the morphology and the
histology studies, the epithelial cell layers from freshly excised pig buccal
mucosa were analysed with light microscopy by means of routine histopathology
analysis (haematoxylin and eosin staining and Toluidine blue staining) and
immunohistochemistry reactions. The organization of desmosomal junctions was
assessed by means of an immunochemical reaction on desmosomes and transmission
electron microscopy. Confocal laser scanning microscopy (CLSM) was used to find
evidence of the location of FD4 in the tissue. Furthermore, the increase of the
FD4 apparent permeability coefficient was quantified by means of Franz diffusion
cells using isolated buccal epithelium to demonstrate the penetration enhancement
properties of the polymer systems. Morphological analysis, performed by light
microscopy, transmission electron microscopy and CLSM, suggests a similar
mechanism of penetration enhancement for both HCS and TMC solutions and for HCS
nanoparticles. Such a mechanism probably involves a repackaging of the epithelial
cells up to the basal membrane and a partial disarrangement of desmosomes. The
cell viability and the nuclear integrity indicated on the semi-thin section
stained with Toluidine blue and by CLSM analysis, respectively, suggest that HCS
as a polymer solution and a nanoparticulate system, and TMC polymer solution, do
not cause cell damage. Trimethyl chitosan and chitosan nanoparticulate systems
were able to increase FD4 permeation across buccal epithelium to a greater extent
than the chitosan solution.
PMID- 17034656
TI - Receptor dependent cellular uptake of synthetic low density lipoprotein by
mammalian cells in serum-free tissue culture.
AB - Low density lipoprotein (LDL) is a normal plasma component, which is of interest
in a number of research areas such as hypercholesterolaemia, drug targeting in
cancer chemotherapy and as a lipid supplement in tissue culture systems.
Currently, however, it can only be obtained by extraction from fresh plasma
samples, which yields only small quantities. Synthetic LDL (sLDL) has been
prepared using readily available lipid components coupled with a synthetic
amphiphatic peptide molecule containing the apoprotein B receptor sequence. sLDL
was capable of supporting the growth of Chinese Hamster Ovary (CHO) and
fibroblast cells in serum-free culture media in a cholesterol-dependent manner
that was related to the presence of the receptor peptide molecule. sLDL could be
fluorescently labelled with 3,3'-dioctadecyloxalocarbocyanine perchlorate (DiO),
and once labelled was assimilated by CHO and fibroblast cells in a time- and
temperature-dependent manner that was dependent upon the presence of the receptor
peptide. In addition, assimilation was reduced by an excess of unlabelled native
LDL. The results indicated that the interaction of sLDL with CHO and fibroblast
cells occurred via a receptor dependent system, most likely the LDL cellular
receptor. sLDL is therefore a useful, easily obtained substitute for native LDL
with potential applications in the areas of drug targeting to cells and serum
free tissue culture systems.
PMID- 17034657
TI - Hypolipidaemic and antiplatelet activity of phenoxyacetic acid derivatives
related to alpha-asarone.
AB - The phenoxyacetic acid derivatives 1-6 [2-methoxy-4-(2-propenyl)phenoxyacetic
acid (1); 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid (2); methyl 2
methoxy-4-(2-propenyl)phenoxyacetate (3); ethyl 2-methoxy-4-(2
propenyl)phenoxyacetate (4); methyl 2-methoxy-5-nitro-4-(2
propenyl)phenoxyacetate (5); ethyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate
(6)] related to alpha-asarone have been reported previously as hypolipidaemic
agents in diet-induced hyperlipidaemic mice. We have aimed to expand the
pharmacological profile of these derivatives by investigating their
hypolipidaemic activity in rats and mice under different experimental conditions.
The antiplatelet activity was tested also in-vitro from blood derived from
consenting healthy volunteers. In normolipidaemic rats, compounds 2, 3 and 5 at
oral doses of 40 and 80 mg kg(-1) significantly decreased total cholesterol and
LDL-cholesterol levels. Moreover, analogues 3 and 5 administered to
hypercholesterolaemic rats at the same doses for seven days also produced a
reduction in the content of these same lipoproteins. In neither case were the
high-density lipoprotein cholesterol and triglyceride concentrations affected.
However, practically all tested compounds were found to be hypocholesterolaemic
agents, and were shown to effectively lower low-density lipoprotein cholesterol
and triglyceride levels in Triton-induced hyperlipidaemic mice at oral doses of
50 and 100 mg kg(-1). In all tests, all animals appeared to be healthy throughout
the experimental period in their therapeutic ranges. Triton-induced
hypercholesterolaemic mice appeared to be a desirable model for this class of
hypolipidaemic drugs. On the other hand, compounds 1, 2, 4 and 5 significantly
inhibited ADP-induced aggregation in-vitro. These findings indicated that all of
these compounds appeared to be promising for the treatment of human
hyperlipidaemia and thrombotic diseases.
PMID- 17034658
TI - Decreased B16F10 melanoma growth and impaired tumour vascularization in BDF1 mice
with quercetin-cyclodextrin binary system.
AB - The aim of this work was to study the inclusion behaviour of a poorly water
soluble bioflavonoid, quercetin, towards sulfobutyl ether-7beta-cyclodextrin. It
also involves angiogenesis inhibition in-vivo in addition to in-vitro human
cancer cell growth inhibition study of quercetin and its cyclodextrin complex.
Drug-cyclodextrin solid inclusion complexes were prepared and characterized in
solution and in the solid state. An in-vitro anti-proliferation study using plain
drug and its solubilized form was carried out on human cancer cell lines of
different origin. Further, an in-vivo tumour growth inhibition study was carried
out using a mouse melanoma model. Histological sections of tumours were examined
for the evaluation of tumour microvessel density. Significant enhancement of the
solubility and dissolution rate of the quercetin, which occurred after
complexation, might be attributed to the decrease in crystallinity of drug.
SBE7betaCD complex of quercetin was more potent for inhibiting cell proliferation
in human erythroleukaemia and cervix cancer cells. Decreased tumour microvessel
density in mouse melanoma after oral quercetin administration led to diminished
tumour cell proliferation. Quercetin-SBE7betaCD complex showed significantly
improved anti-cancer activity at much lower concentration than the plain drug,
providing evidence for dose reduction without affecting therapeutic efficacy when
using cyclodextrin carriers.
PMID- 17034659
TI - Metabolism of troglitazone in hepatocytes isolated from experimentally induced
diabetic rats.
AB - Troglitazone (TGZ), the prototype 2,4-thiazolidinedione antidiabetic agent, is
associated with hepatotoxicity in patients with Type 2 diabetes. Although the
mechanism of toxicity has not been established, alterations in the clearance of
TGZ from in-vitro hepatocyte cultures through metabolic conjugation reactions are
believed to modulate the toxicity of the compound. In this study, the metabolism
of TGZ in freshly isolated hepatocytes from the fat-fed streptozotocin-treated
rat model of Type 2 diabetes is described. Biochemical parameters such as
cellular reduced glutathione content, content of cytochromes P450 and b5, and the
expression of glutathione-S-transferase alpha (subunits Ya and Yc2) were not
affected by the induced diabetes. TGZ was metabolized primarily to a sulfonate, a
quinone and a glucuronide in both control and experimentally diabetic animals.
However, metabolism after induction of diabetes was characterized by a moderate
increase in sulfation, a decrease in the elimination half-life of TGZ and the
absence of the minor metabolites of TGZ, notably the glutathione adduct of the
putative reactive intermediate (m/z = 747 (M + H)+; m/z = 745 (M - H)-).
PMID- 17034660
TI - Effect of the administration of tiagabine and gabapentin on rabbit
electroencephalogram activity.
AB - New generation antiepileptic drugs, including gabapentin and tiagabine, are used
in monotherapy or in combination with other drugs for specific seizure types. The
multidirectional mechanism of activity and varied pharmacological properties of
these drugs suggest that they could also be used in the therapy of other
diseases. A possible limitation of new generation antiepileptic drugs is the
incidence of CNS-related adverse effects. Few studies have assessed the effect of
new antiepileptic drugs on electroencephalogram (EEG) recordings in subjects
using these drugs for diseases other than epilepsy. The aim of this study was to
determine the effects of tiagabine and gabapentin on EEG recordings from the
midbrain reticular formation, dorsal hippocampus and frontal cortex in rabbits.
Tiagabine was administered orally at a single dose of 5 and 20 mg kg(-1), or
repeatedly at a dose of 5 mg kg(-1) (twice a day) for 14 days. Gabapentin was
administered orally at a single dose of 25 and 100 mg kg(-1), or repeatedly at a
dose of 25 mg kg(-1) (twice a day) for 14 days. Both tiagabine and gabapentin
caused changes indicative of CNS inhibitory properties, which may be associated
with the adverse effects of the drugs. After repeated doses of the drugs, the
changes in EEG recordings were less pronounced than after single doses, which may
indicate adaptive changes. The hippocampus was found to be the least sensitive to
the effect of gabapentin.
PMID- 17034662
TI - Relaxant effect of Crocus sativus (saffron) on guinea-pig tracheal chains and its
possible mechanisms.
AB - As indicated in ancient Iranian medical books, Crocus sativus has therapeutic
effects on respiratory diseases. The relaxant effect of this plant has been
observed also on smooth muscles in previous studies. Therefore, in this study the
relaxant effects of aqueous-ethanolic extracts of C. sativus and one of its main
constituents, safranal, were examined on guinea-pig tracheal chains. The relaxant
effects of four cumulative concentrations of aqueous-ethanolic extract (0.15,
0.3, 0.45, and 0.60 g %) and safranal (0.15, 0.30, 0.45, and 0.60 mL 0.2 mg mL(
1) solution) in comparison with saline, as negative control, and four cumulative
concentrations of theophylline (0.15, 0.30, 0.45, and 0.60 mM), as positive
control, were examined using guinea-pig precontracted tracheal chains. The
tracheal chains had been precontracted by three different methods. Group 1 had
been precontracted using 10 microM methacholine. The other two groups had been
precontracted using 60 mM KCl at two different conditions: non-incubated tissues
(group 2) and tissues incubated with 1 microM propranolol, 1 microM
chlorpheniramine and 1 microM atropine (group 3) (for each group, n = 6). In
group 1 all concentrations of theophylline, extract and safranal showed
significant relaxant effects compared with saline (P < 0.05 to P < 0.001). In
group 2 theophylline, extract and safranal showed concentration-dependent
relaxant effects also compared with saline (P < 0.05 to P < 0.001 for different
concentrations except two low concentrations of safranal). However, in group 3
the extracts of C. sativus showed a weak relaxant effect (P < 0.05 only for the
highest concentration). The effects of the last concentration of safranal (0.60
mL 0.2 mg mL(-1) solution) in group 1, and all its concentrations in group 2 were
significantly lower than those of theophylline (P < 0.05 to P < 0.001). In
addition, the effects of safranal 0.45 and 0.60 mL 0.2 mg mL(-1) solution in
groups 1 and 2 were significantly lower than that of C. sativus extract. There
were significant correlations between the relaxant effects and concentrations for
extract, safranal and theophylline in all experimental groups (P < 0.001 for all
cases). These results showed a potent relaxant effect of C. sativus on tracheal
chains of guinea-pigs that was comparable to or even higher than that of
theophylline at the concentrations used. The results indicated that safranal was,
at least in part, responsible for the relaxant effect of C. sativus.
PMID- 17034661
TI - Protective effect of rutin on lipids, lipoproteins, lipid metabolizing enzymes
and glycoproteins in streptozotocin-induced diabetic rats.
AB - The protective role of rutin on lipids, lipoproteins, lipid metabolizing enzymes
and glycoproteins in streptozotocin-induced diabetic rats has been studied. A
single intraperitoneal injection of streptozotocin (50 mg kg(-1)) to rats led to
a significant (P < 0.05) increase in the levels of lipids (cholesterol,
triglycerides, free fatty acids and phospholipids) in plasma and tissues (liver,
kidney, heart and brain). The levels of low density and very low density
lipoprotein (LDL and VLDL, respectively) cholesterol were increased, whereas the
levels of high density lipoprotein (HDL) cholesterol were decreased significantly
(P < 0.05) in plasma. The activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG
CoA) reductase increased significantly (P < 0.05) in liver, kidney and heart, and
the activity of lipoprotein lipase (LPL) and lecithin cholesterol acyltransferase
(LCAT) decreased significantly (P < 0.05) in the plasma of diabetic rats.
Streptozotocin injection also increased the levels of glycoproteins such as
hexose, hexosamine, fucose and sialic acid in plasma, liver and kidney. Oral
administration of rutin to streptozotocin-induced diabetic rats significantly (P
< 0.05) decreased the levels of lipids in plasma and tissues. The levels of
plasma HDL-cholesterol increased and the levels of LDL- and VLDL-cholesterol
decreased significantly (P < 0.05). The activity of HMG CoA reductase decreased
in the tissues and the activity of plasma LPL and LCAT increased significantly (P
< 0.05). The levels of glycoproteins were found to be significantly (P < 0.05)
decreased in plasma, liver and kidney of rutin-treated diabetic rats. Rutin
administration to normal rats did not exhibit any significant (P < 0.05) changes
in any of the parameters studied. In conclusion, the beneficial effect of rutin
on lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins could be
due to its antioxidant property.
PMID- 17034663
TI - Protective effects of the Alisma orientalis extract on the experimental
nonalcoholic fatty liver disease.
AB - The aim of this investigation was to evaluate the efficacy of Alisma orientalis
methanolic extract (AOME) on the experimental nonalcoholic fatty liver disease
(NAFLD) induced by high-fat diet. Rats were fed with high-fat diet for six weeks
and then gavaged the AOME for another six weeks. Typical pathological symptoms of
NAFLD occurred in the high-fat diet rats. Administration with the AOME (150,300
and 600 mg kg (-1)) markedly decreased the serum and liver lipids; the high level
of fasting serum glucose was reduced and insulin resistance was improved. The
AOME treatment was also helpful in preventing the oxidative stress by lessening
lipid peroxidation and activating antioxidant enzymes. Markers of the liver
injury, aminotransferase abnormalities and hepatomegaly were improved and
morphological changes, such as liver steatosis, mixed inflammation and collagen
deposition, were lessened in rats treated with the AOME. These results suggested
that the AOME showed hepatoprotective effects on NAFLD and may be a potential
clinical application for treatment of this chronic liver disease.
PMID- 17034664
TI - Novel selective cytotoxicity of wild sarsaparilla rhizome extract.
AB - Among six fractions, including total extract and fractions of hexane, ethyl
acetate, butanol, water and boiling water extracted and separated from wild
sarsaparilla rhizome, the hexane fraction (HRW) was the most effective in
eliminating four different human cancer cell lines with cellular viability less
than 6.8%. HRW exhibited the highest potency against human leukaemia cells with
an IC50 (concentration that inhibited the growth rate of cells by 50%) of 3.3 +/-
0.3 microg mL(-1), which was 17.6-fold smaller than that against normal human
umbilical vein endothelial cells (IC50, 58.0 +/- 1.5 microg mL(-1)). For its rich
natural resources, simple extraction procedure and high yield (3.2%), HRW has the
potential to be developed as a selective anti-cancer nutraceutical or
pharmaceutical natural health product with low side effects and high economical
return.
PMID- 17034665
TI - The inhibition of paw oedema formation caused by the oil of Copaifera multijuga
Hayne and its fractions.
AB - Two oils exuded from a Copaifera multijuga Hayne tree (Leguminosae
Caesalpinoideae), collected from the same plant, but in different periods of the
year, and the hexanic, dichloromethanic and methanolic fractions of one of these
oils were analysed by high-resolution gas chromatography (HRGC) and HRGC coupled
with mass spectrometry (HRGC-MS). In addition, the in-vivo preliminary anti
oedematogenic actions of the oil and some fractions of it were assessed against
carrageenan- and bradykinin-induced oedema formation in the rat paw. Twenty-seven
sesquiterpenes and six diterpenes were identified, beta-caryophyllene, alpha
copaene and copalic acid being the main components. The dichloromethanic and
methanolic fractions obtained from C. multijuga oil given by the intraperitoneal
route caused a significant inhibition of paw oedema caused by carrageenan with
inhibition of 49 +/- 13% and 64 +/- 9 %, respectively. Likewise, dexamethasone
(the positive control drug) also greatly inhibited carrageenan-induced paw oedema
formation (60 +/- 4% at 2 h). The hexanic fraction also significantly inhibited
(50 +/- 6%) the paw oedema formation caused by bradykinin. These results suggest
the presence of still non-identified active terpene compounds in the oil of C.
multijuga that exhibit anti-oedematogenic properties. Of note, the yield of these
compounds and the pharmacological actions of the oil, exhibited great seasonal
variations, a relevant aspect that should be carefully observed for the correct
medicinal use of this plant by the population.
PMID- 17034666
TI - Protective effect of Mediterranean fish oil extracts on heat-induced denaturation
of albumin.
AB - Three oily extracts, obtained by acetone extraction from the entrails of
different varieties of Mediterranean fishes, such as mackerel (Scomber scombrus),
sardine (Sardina pilchardus) and horse mackerel (Trachurus mediterraneus), were
characterized to determine their unsaturated fatty acid content. In an in-vitro
model, their inhibitory effect was then evaluated against protein aggregation and
their protective efficacy against heat-induced albumin denaturation assessed. The
fish oil extracts tested in this study presented a significant amount of
unsaturated fatty acids; in particular the extract obtained from the entrails of
horse mackerel proved to have higher concentrations of DHA (docosahexaenoic acid)
and oleic acid compared with the other two oils. The in-vitro study revealed an
interesting protective effect of the oil extracts (particularly the horse
mackerel extract) against heat-induced denaturation of albumin.
PMID- 17034667
TI - N, N' (4,5-dihydro-1h-imidazol-2-yl)3-aza-1,10-decane-diamine and N, N'(4,5
dihydro-1H-imidazol-2-yl)3-aza-1, 10-dodecane-diamine antagonize cell
proliferation as selective ligands towards topoisomerase II.
AB - New alkyl imidazoline derivatives have been synthesized as potential anti-cancer
agents. The anti-proliferative activity of these compounds, evaluated against
representative human haematological and solid neoplastic cell lines, showed that
N, N'-di (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-decane-diamine (8) and N, N'-di
(4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-dodecane-diamine (9) were the most
active compounds; in fact, they inhibited the cell proliferation at submicromolar
concentrations. In enzyme assays, compound 9 turned out to be an inhibitor of
topoisomerase II at concentrations comparable with those of the reference
topoisomerase II inhibitor, etoposide.
PMID- 17034669
TI - Difficult pain syndromes: bone pain, visceral pain, and neuropathic pain.
AB - Cancer pain is prevalent in approximately two thirds of all cancer patients and
can undermine the quality of life in this patient population. Uncontrolled pain
can cause physical as well as psychological distress in cancer patients. As the
disease progresses in cancer, pain and suffering increase. Knowledge about pain
management is paramount in the comprehensive treatment of cancer patients.
Difficult cancer pain syndromes may arise from interruption of bone, viscera, and
neural structures by malignant spread of the disease. Familiarity with opioids,
adjuvants, and procedures that can abate pain in cancer patients is discussed in
a practical manner for clinical application in this text.
PMID- 17034670
TI - New approaches to chemotherapy-induced nausea and vomiting: from
neuropharmacology to clinical investigations.
AB - Nausea and vomiting are considered to be among the most distressing consequences
of cytotoxic chemotherapies. Currently, there are several novel 5-HT(3) receptor
antagonists for the treatment of chemotherapy-induced nausea and vomiting (CINV),
including ondansetron, granisetron, and dolasetron. These agents provide
significant improvement in the management of acute emesis but are ineffective at
preventing delayed emesis. In 2003, a new 5-HT(3) receptor antagonist,
palonosetron HCL (Aloxi), was introduced to the U.S. market. Palonosetron was
found to be effective in preventing delayed CINV. Indeed, palonosetron was the
first and only 5-HT(3) receptor antagonist approved by the FDA for the prevention
of both acute and delayed CINV. More recently, studies on the role of substance P
in the emetic process led to the development of aprepitant (Emend) for the
prevention of delayed emesis in combination with 5-HT(3) receptor antagonists.
Despite these major advances, CINV remains uncontrolled in some patients. Current
efforts are focused on treating refractory emesis and include both the clinical
evaluation of compounds marketed for other indications and the preclinical
evaluation of novel molecules targeting other transmitters in the emetic pathway.
Ongoing work in pharmacogenomics has postulated several candidate genes that
could be involved in emetic sensitivity and responsiveness to antiemetic therapy.
Investigations into the pharmacogenomics of CINV may someday be able to aid in
the identification of high risk patients and patients unlikely to respond to
conventional therapies.
PMID- 17034671
TI - Treatment of mucositis, including new medications.
AB - Mucositis is a clinically important and sometimes dose-limiting complication of
cancer therapy. Mucositis lesions can be painful, affect nutrition and quality of
life, lead to sepsis, and have significant economic impact. Recent modeling of
the toxicity has been based on the continuum of clinical signs and symptoms of
mucositis involving the alimentary tract, including both oral and
gastrointestinal sites. The pathogenesis of oral and gastrointestinal mucositis
is multifactorial and complex. In recent years, there has been a substantial
increase in both basic and clinical research related to mucosal injury in cancer
patients. Since most of this research has been directed to oral mucositis, the
present review principally addresses this component of the toxicity. Morbidity,
economic impact, pathogenesis and clinical course of mucositis are discussed. In
addition, several agents in clinical development for mucositis are discussed in
the context of the current pathobiologic model as well as the recently updated
evidence-based clinical management guidelines.
PMID- 17034672
TI - Constipation and diarrhea in patients with cancer.
AB - Constipation and diarrhea are both common problems in patients with advanced
cancer. They are source of major morbidity and distress. Constipation is,
overall, more common that diarrhea. Diarrhea may be severe and, in some cases,
associated with life-threatening dehydration and electrolyte abnormalities.
Indeed, with some of the newer chemotherapy agents, this is a problem seen with
increasing frequency. Oncologists must be familiar with the common causes of
constipation and diarrhea in cancer patients and the strategies to evaluate and
manage these common and distressing symptoms. Both with constipation and
diarrhea, there is a differential diagnosis. In many cases, management can be
complex and challenging. Approaches to diagnosis, evaluation, and management are
reviewed.
PMID- 17034673
TI - Dyspnea.
AB - Dyspnea, defined as uncomfortable or labored breathing, is a common and often
devastating cause of distress for patients and their caregivers with advanced
cancer and other life-threatening illnesses. The mechanism by which dyspnea
develops is not fully understood, but it involves integration of the central
respiratory complex with the sensory (perceptual) cortex. The gold standard of
diagnosis is patient self-report. Careful assessment should be undertaken to
identify reversible existing causes. Systemic opioids are the first-line therapy
for symptomatic management, along with other general comfort measures
(positioning, cool air, calming environment). Medical or surgical management can
be directed toward underlying causes. Advanced care planning should include
discussions concerning the burdens and benefits of medical/surgical management of
underlying causes of dyspnea to more effectively direct goals of care. This
article reviews current literature on dyspnea, with a focus on items published
since 2000.
PMID- 17034674
TI - Cancer-related fatigue: the evidence base for assessment and management.
AB - PURPOSE: Cancer-related fatigue contributes to negative outcomes relative to
psychosocial and symptom distress, functional status, and quality of life, and
yet it is often underdiagnosed and management is frequently suboptimal. DESIGN:
Systematic database searches were conducted, and primary research reports and
meta-analyses of quantitative studies of interventions for fatigue published in
English were identified and critically examined. RESULTS: This paper reviews the
etiology and evaluation of cancer-related fatigue and analyzes current empirical
evidence supporting pharmacologic and nonpharmacologic techniques for its
management. DISCUSSION: A variety of pharmacologic and nonpharmacologic
techniques to manage cancer-related fatigue have been studied, although most of
the evidence is from single-arm pilot studies with small sample sizes, rather
than from adequately powered, multicenter, randomized controlled trials.
Continued research in ethnically and racially diverse samples is needed to
identify the interventions that are most effective in specific cancer
subpopulations and to develop and test interventions for fatigue at each phase in
the illness trajectory.
PMID- 17034675
TI - Depression and anxiety.
AB - Anxiety and depression are common in patients with cancer and in palliative care
settings. These symptoms can be reactive to the illness or can be related to the
direct physiologic effects of the disease or to drug therapies. Effective
treatment of these symptoms includes both psychopharmacologic and
psychotherapeutic approaches. The newer antidepressants, anxiolytics, and
hypnotics are better tolerated and can be continued safely if necessary, or they
can be reduced and discontinued as symptoms improve.
PMID- 17034676
TI - Interdisciplinary spiritual care for seriously ill and dying patients: a
collaborative model.
AB - Spirituality is essential to healthcare. It is that part of human beings that
seeks meaning and purpose in life. Spirituality in the clinical setting can be
manifested as spiritual distress or as resources of strength. Patients' spiritual
beliefs can impact diagnosis and treatment. Spiritual care involves an intrinsic
aspect of care, which underlies compassionate and altruistic caregiving and is an
important element of professionalism amongst the various healthcare
professionals. It also involves an extrinsic element, which includes spiritual
history, assessment of spiritual issues, as well as resources of strength and
incorporation of patients' spiritual beliefs and practices into the treatment or
care plan. Spiritual care is interdisciplinary care-each member of the
interdisciplinary team has responsibilities to provide spiritual care. The
chaplain is the trained spiritual care expert on the team. Optimally, all
healthcare professionals, including the chaplain, on the team interact with each
other to develop and implement the spiritual care plan for the patient in a fully
collaborative model.
PMID- 17034677
TI - Communication at times of transitions: how to help patients cope with loss and re
define hope.
AB - Patients undergo multiple transitions during the course of their cancer care.
Oncologists are uniquely positioned to help patients through these transitions.
When patients' situations change, they must cope with loss and associated
negative emotions. They then are able to redefine hope. During transitions,
patients want their oncologists to provide biomedical information, show that they
care about and understand them as individuals, and balance hope and realism.
Eliciting concerns and expressing empathy shows patients that their oncologist
cares about and understands them and also helps patients to cope with the loss
and negative emotions that transitions create. Oncologists can maintain hope by
being sensitive to what patients are ready to hear when, and by helping them
discover and identify realistic hopes. This is accomplished with the Ask-Tell-Ask
and Hope for the Best, Prepare for the Worst techniques, and most importantly by
being curious about patients' hopes and fears.
PMID- 17034678
TI - Complementary medicine in palliative care and cancer symptom management.
AB - Complementary and alternative medicine (CAM) use among cancer patients varies
according to geographical area, gender, and disease diagnosis. The prevalence of
CAM use among cancer patients in the United States has been estimated to be
between 7% and 54%. Most cancer patients use CAM with the hope of boosting the
immune system, relieving pain, and controlling side effects related to disease or
treatment. Only a minority of patients include CAM in the treatment plan with
curative intent. This review article focuses on practices belonging to the CAM
domains of mind-body medicine, CAM botanicals, manipulative practices, and energy
medicine, because they are widely used as complementary approaches to palliative
cancer care and cancer symptom management. In the area of cancer symptom
management, auricular acupuncture, therapeutic touch, and hypnosis may help to
manage cancer pain. Music therapy, massage, and hypnosis may have an effect on
anxiety, and both acupuncture and massage may have a therapeutic role in cancer
fatigue. Acupuncture and selected botanicals may reduce chemotherapy-induced
nausea and emesis, and hypnosis and guided imagery may be beneficial in
anticipatory nausea and vomiting. Transcendental meditation and the mindfulness
based stress reduction can play a role in the management of depressed mood and
anxiety. Black cohosh and phytoestrogen-rich foods may reduce vasomotor symptoms
in postmenopausal women. Most CAM approaches to the treatment of cancer are safe
when used by a CAM practitioner experienced in the treatment of cancer patients.
The potential for many commonly used botanical to interact with prescription
drugs continues to be a concern. Botanicals should be used with caution by cancer
patients and only under the guidance of an oncologist knowledgeable in their use.
PMID- 17034679
TI - Recovery issues in cancer survivorship: a new challenge for supportive care.
AB - The growing population of cancer survivors represents a clear challenge to
clinicians and researchers to look beyond the search for a cure and to address
the multifaceted needs of those living with and beyond a cancer diagnosis. Common
sequelae that disrupt the psychosocial aspects of life for adult cancer survivors
after primary treatment include: fatigue; cognitive changes; body image; sexual
health and functioning; infertility; fear of recurrence; PTSD and stress
syndromes; family/caregiver distress; socioeconomic issues; and distress,
anxiety, and depression. Psychosocial interventions, particularly group-based
interventions and physical activity programs, have shown great promise in
improving these outcomes. Future research will identify even better targeted,
more efficacious, and more cost effective programs and disseminate them into
cancer care settings. Healthcare providers must realize that they serve as vital
gatekeepers to services that will help optimize cancer survivors' psychosocial as
well as physical outcomes. Addressing these issues in the post-treatment period
represents the new challenge to supportive care.
PMID- 17034680
TI - New tools to fight disease should be celebrated, but we also need the systems and
the people to deliver them.
PMID- 17034682
TI - Surgical collaboration between rich and poor - what does the future hold?
PMID- 17034683
TI - College of Surgeons of East, Central and Southern Africa.
PMID- 17034684
TI - Management of hydrocephalus.
PMID- 17034685
TI - The acute abdomen and HIV.
AB - HIV-related disease continues to increase and presents the greatest single
challenge to the medical practitioner seeking to alleviate suffering in the
developing world. As a result, the practice of surgery cannot ignore the impact
of HIV and must assess the implications of this new disease. Although much has
been written of HIV-related surgical pathology, the preponderance of the
literature reflects the experience of surgeons working in well-equipped hospitals
in the First World where HIV prevalence is low and where there is ready access to
a multiplicity of drug therapies and nursing backup.
PMID- 17034686
TI - Sickle cell disease in surgery.
PMID- 17034687
TI - Fournier gangrene.
AB - Fournier gangrene is a necrotizing infection involving the soft tissues of the
male genitalia. It was first described in 1764 by Baurienne and given its
eponymous name after Jean-Alfred Fournier in 1883 presented a case of perineal
gangrene in an otherwise healthy young man. While only 600 cases of Fournier
gangrene have been reported in the world literature since 1996, it is a common
and serious disease in Africa. In Maputo Central Hospital alone, between 12 and
16 cases are admitted every year and treated with a 20% mortality. The typical
patient is an elderly male in his sixth or seventh decade with co-morbid
diseases. While considered to affect males only, a similar condition may
occasionally affect the female genitalia.
PMID- 17034688
TI - Postpartum care attendance at a rural district hospital in Zambia.
AB - Postpartum care is an important tool in both preventive and promotive maternal
health care. We studied the postpartum care attendance rate in 540 women who
delivered at a district hospital in Zambia. Forty-two percent of the women
attended postpartum care within six weeks of delivery. Women who did not come for
postpartum care were older and had to travel more hours to the hospital than
women who attended postpartum care. The low postpartum care attendance rate could
be increased if health workers provided mother and child health care in an
integrated way and were aware that recently delivered women also visit the
hospital for reasons other than postpartum care. Health workers need to inform
pregnant women about the benefits of postpartum care and make them feel welcome
to attend this health service, also when women decide to deliver at home.
PMID- 17034689
TI - HIV awareness and traditional birth practice in the Niger delta area of Nigeria.
PMID- 17034690
TI - The neurodevelopmental abilities of very-low-birthweight children in Trinidad,
West Indies.
AB - Neurodevelopmental abilities of 33 very-low-birthweight (VLBW) Trinidadian
children and randomly selected matched pairs of classmates who were of normal
birth weight were tested in 1998 at ages 68-88 months, using the McCarthy Scales
of Children's Abilities. The 1 min Apgar score was significantly lower in the
VLBW children, 6.5 (SD 1.0) versus 7.7 (SD 1.27), P 0.05).
CONCLUSION: IL-1alpha (-889) gene polymorphism is related to pneumoconiosis.
Workers with IL-1alpha (-889) allele 2 are susceptible to the pneumoconiosis. The
relationship between IL-1beta (-511), IL-1Ra (+2018), IL-1Ra VNTR genes
polymorphisms and pneumoconiosis are not found.
PMID- 17034725
TI - [Application of double-level non-invasive positive ventilation in rehabilitation
of patients with coal workers' pneumoconiosis].
PMID- 17034726
TI - [Relationship between single nucleotide polymorphisms of NRAMP1 gene and
susceptibility to pulmonary tuberculosis in workers exposed to silica dusts].
AB - OBJECTIVE: To explore the relationship between polymorphisms of natural
resistance-associated macrophage protein 1 (NRAMP1) gene and genetic
susceptibility of pulmonary tuberculosis (PTB) in workers exposed to silica
dusts. METHODS: A 1:2 case control study of 61 male workers with PTB (50
silicosis patients and 11 unsilicosis workers) as the case group and 122 male PTB
free workers (100 silicosis patients and 22 unsilicosis workers) as the control
group was conducted with the frequency matched for age of +/- 5 years, the job,
the silica exposure, and the condition of cigarette smoking and alcohol drinking.
The polymerase chain reaction-restrained fragment length polymorphism technique
(PCR-RFLP) was used to detect the single nucleotide polymorphisms (SNPs) of
NRAMP1 INT4 and D543N. RESULTS: There was a 2.73 times (95% CI: 1.32
approximately 5.64) increased risk of silicosis for individuals with C allele of
NRAMP1 INT4 compared with individuals carrying homozygote (G/G), while SNPs of
NRAMP1 D543N was not associated with PTB (P > 0.05). CONCLUSION: The G > C
mutation of intron 4 of NRAMP1 gene might be a susceptible factor of silica for
the workers exposed to PTB.
PMID- 17034727
TI - [Relationship between genetic polymorphism of interleukin-6 and pneumoconiosis].
AB - OBJECTIVE: To explore the relationship between interleukin-6 (IL-6) (-634C/G)
genetic polymorphisms and the pneumoconiosis. METHODS: A total of 104 male stage
I pneumoconiosis patients diagnosed by the Pneumoconiosis Diagnosis Expert Panel
according to the Chinese National Diagnosis Criteria of Pneumoconiosis (GBZ 70 -
2002) were selected. The pneumoconiosis comprised 66 silicosis and 38 coal
worker' pneumoconiosis (CWP). A total of 122 workers exposed to same dusts as the
patients but without pneumoconiosis including 77 exposed to silica dusts and 45
to coal dusts were selected. The patients and the controls had the same dust
exposure history. The peripheral venous blood was drawn from each subject. The IL
6 (-634C/G) genetic polymorphisms were detected by polymerase chain reaction
restriction fragment length polymorphisms (PCR-RFLP) techniques. RESULTS: The
frequencies of IL-6 (-634C/G) (CC, CG and GG) genotypes were 66.7%, 19.7% and
13.6% in silicosis group, 42.9%, 42.9% and 14.2% in silica dust exposure group,
73.7%, 18.4% and 7.9% in CWP group, 51.1%, 35.6% and 13.3% in coal dust exposure
group respectively. The statistical analysis indicated that there was significant
difference in the frequencies of IL-6 (-634C/G) (CC, CG and GG) genotypes between
silicosis patients and workers exposed to silica dusts (P < 0.05). CONCLUSION: IL
6 (-634 C/G) genetic polymorphisms might play a role in the occurrence of
silicosis.
PMID- 17034728
TI - [Determination and analysis of silica particles surface alumino-silicate
occlusion].
AB - OBJECTIVE: To investigate the methods of determining aluminum silicate coated on
the surface of silica particles and analyze the role of surface occlusion on
development of silicosis. METHODS: Respirable dust samples were collected on
filters using 2 L/min flow in tungsten mines and pottery factories of Jiangxi
province, and tin mines of Guanxi province. Dust particles were analyzed by a
multiple-voltage scanning electron microscopy-energy dispersive X-ray
spectroscopy (MVSEM-EDS) using 20 KeV and 5 KeV electron beam accelerating
voltages. Changes in the silicon to aluminum X-ray line intensity ratio between
the two voltages are compared particle by particle. This provided an index that
distinguishes a silica particle that was homogeneously aluminum-contaminated from
a clay coated silica particle. RESULTS: The total of 3,982 dust particles from 47
dust samples of seven pottery factories, three tin mines and three tungsten mines
were analyzed in this study. Significant difference of aluminum silicate coated
on the surface of silica particle was shown between particles from pottery
factories and tin mines. The average sample percentage of respirbale-sized silica
particles alumino-silicate occlusion in the pottery factories (45%) was higher
than that in the tin mines (18%) and tungsten mines (13%). CONCLUSION: Higher
percentages silica particles alumino-silicate occlusion is observed in the
pottery factories than that in metal mines. These surface analysis results help
to understand differences in risk of silicosis when exposure is normalized to
cumulative respirable surface silica dust.
PMID- 17034729
TI - [Relationship between dust exposure and chronic obstructive pulmonary diseases
and heat shock protein 72 and 73 in lymphocytes among coal miners].
AB - OBJECTIVE: To assess the expression of Hsp72 and Hsp73 in chronic obstructive
pulmonary disease (COPD) and to evaluate their roles in damage from coal dust
exposure. METHODS: A case control study of 50 coal miners suffering from COPD and
50 healthy coal miners were selected from one coal mine. The levels of Hsp72 and
Hsp73 in peripheral blood lymphocytes were determined by flow cytometry for all
subjects. RESULTS: (1) The expression of basic Hsp72 of peripheral blood
lymphocytes for patients and controls was not different from that inducible
expressed Hsp72 by 42 degrees C heat stress or by BPDE exposure. (2) The
expression of Hsp72 in COPD patients (17.7 +/- 4.9) was significantly lower than
that in healthy coal miners (22.6 +/- 10.0) (P < 0.01). On the other hand, the
expression of Hsp73 in COPD patients (33.5 +/- 11.7) was higher than that in
healthy coal miners (19.6 +/- 5.9) (P < 0.01). (3) A-positive relationship
between the expression of Hsp72 and cumulative inhaling coal dust exposure was
observed. No relationship was found between Hsp73 and cumulative inhaling coal
dust exposure. CONCLUSION: The decreased expressions of Hsp72 in peripheral blood
lymphocytes of COPD coal miners.
PMID- 17034730
TI - [Effects of taurine on type I and III collagen expression in rats lung exposed to
silica].
AB - OBJECTIVE: To evaluate the effects of taurine in diet on the expression of type I
and III collagen and collagen ratio at different time points in rats lung by
image process technology. METHODS: Wistar rats were randomly divided into three
groups: the saline instilled with a control diet (the saline treated group);
silica instilled with a control diet (the silica treated group); and silica
instilled with a diet containing 2.5% taurine (the taurine treated group). Animal
models were established by the direct tracheal instillation of silica into rat
lungs exposed surgically. The taurine concentration of serum was analyzed by
means of HPLC. Paraffin embedded lung sections were stained with Sirius red.
Polarization microscopy and Image Pro Plus Version 4.5 for windows were used for
detecting type I and III collagen. RESULTS: The concentration of taurine in serum
of the taurine treated group was significantly elevated compared to the saline
treated and silica treated group (P < 0.05 or P < 0.01). Sirius red polarization
microscopy showed that type I and III collagen positive area percentage were
elevated in the silica treated rats compared with the saline treated group. On
the 7th, 14th, 21st, 28th day after silica instillation type I collagen positive
area percentage was increased by 3.84, 3.77, 3.73, 9.83 respectively (P < 0.01),
and type III collagen positive area percentage were elevated by a little in the
silica treated rats compared with saline treated group. The taurine treatment
significantly decreased elevation of silica type I collagen positive area
percentage of lung by 2.39, 1.62, 7.13 at the 7th, 21st, 28th day respectively (P
< 0.05 or P < 0.01), and type III collagen positive area percentage of lung by
2.62 at the 28th day (P < 0.05) compared with the silica treated group. The ratio
of type I to III collagen was increased from the 7th day to 28th day after silica
instillation, and reached 1.87 at the 28th day with the maximal ratio in the
silica-treated group. CONCLUSION: Treatment with taurine can effectively
attenuate type I and III collagen expression in the rat lung induced by silica
particles at different time points in our study.
PMID- 17034731
TI - [Effects of dusts on workers' health in enzyme production plants].
AB - OBJECTIVE: To assess the health effects of dusts in enzyme production plants.
METHODS: The concentration of enzyme-containing dusts, the enzyme and the wheat
containing dusts and their health effects on workers were investigated in three
enzyme production plants. Air samples were collected by high volume sampler and
personal sampler. Total dust was weighed and its content of enzyme was analyzed
by enzyme activity method. Health effects were assessed by the questionnaire, the
pulmonary function and the skin prick test. RESULTS: It was found that the
geometric mean of enzyme-containing dust was 8.91 mg/m(3), the industrial enzyme
was 1.68 mg/m(3), and the wheat-containing dust was 6.93 mg/m(3). The enzyme
containing dust higher than 20 mg/m(3) caused eye symptoms. The wheat-containing
dust at 6.93 mg/m(3) might result in skin and nose symptoms. The sensitization
could be observed in enzyme and wheat exposed workers. CONCLUSION: Adverse
effects may arise for the health of the workers if the concentration of enzyme
containing dusts and the wheat-containing dusts is up to a certain limit and it
is necessary to make the limit of these indexes.
PMID- 17034732
TI - [Investigation on psychological health of workers in a steel factory].
PMID- 17034733
TI - [Dynamic analysis of dusts in Rush-mat industries].
PMID- 17034734
TI - [Effects of professional exposure to medicinal chemicals on women's health].
PMID- 17034735
TI - [Preliminary research on effects of subchronic exposure to hydroxylammonium
nitrate on tests germ cells of male rats].
PMID- 17034736
TI - [Expression of lysozyme of macrophages of alveolus in rats exposed to quartz].
PMID- 17034737
TI - [Research on detection of nodules in lungs with low-dosage multiple-layer CT
maximal intensity projection].
PMID- 17034738
TI - [Spiral CT in diagnosis of pneumoconiosis pulmonary heart disease in coal
workers].
PMID- 17034739
TI - [Relationship between pulmonary ventilation of patients with molybdenum silicosis
and manifestation in chest X-ray].
PMID- 17034740
TI - [Determination of sixteen types of polycyclic aromatic hydrocarbon in
atmosphere].
PMID- 17034741
TI - [Influential factors for determination of free silicon dioxide in dusts and
improvement].
PMID- 17034742
TI - [Advance of research on p53 gene and regulation of DNA injury signals].
PMID- 17034743
TI - [Health proclamation of workers].
PMID- 17034744
TI - [Occupational health and medical surveillance principles for workers exposed to
silicon dusts in metal industry of Germany].
PMID- 17034745
TI - [Discussion on revision of exposure limits of quartz dusts in mining and
quarrying industries in Spain].
PMID- 17034746
TI - [Quality control for evaluation of effect of control over occupational hazards in
construction projects].
PMID- 17034747
TI - Errors and violations in relation to motorcyclists' crash risk.
AB - This study was conducted to: (a) develop a questionnaire that reliably measures
the behaviour of motorcyclists and (b) test which types of behaviour predict
motorcyclists' crash risk. A Motorcycle Rider Behaviour Questionnaire (MRBQ),
consisting of 43 items to measure the self-reported frequency of specific riding
behaviours, was developed and administered to a sample of motorcyclists (N=8666).
Principal components analysis revealed a 5-factor solution (traffic errors,
control errors, speed violations, performance of stunts and use of safety
equipment). Generalised linear modelling showed that, while controlling for the
effects of age, experience and annual mileage, traffic errors were the main
predictors of crash risk. For crashes in which respondents accepted some degree
of blame, control errors and speed violations were also significant predictors of
crash risk. Implications of the findings are discussed in relation to deciding
which countermeasures may be most effective at reducing motorcycle casualty
rates.
PMID- 17034748
TI - The prevalence of, and factors associated with, serious crashes involving a
distracting activity.
AB - The study's objectives were to determine the prevalence and types of distracting
activities involved in serious crashes, and to explore the factors associated
with such crashes. We interviewed 1367 drivers who attended hospital in Perth,
Western Australia between April 2002 and July 2004 following a crash. A
structured questionnaire was administered to each driver and supplementary data
were collected from ambulance and medical records. Over 30% of drivers (433,
31.7%) cited at least one distracting activity at the time of crashing and driver
distraction was reported to have contributed to 13.6% of all crashes. The major
distracting activities were conversing with passengers (155, 11.3%), lack of
concentration (148, 10.8%) and outside factors (121, 8.9%). Using logistic
regression, a distracting activity at the time of a crash was significantly more
likely among drivers with shorter driving experience (0-9 years, 38.3% versus
>or=30 years, 21.0%, p<0.001). Distracting activities at the time of serious
crashes are common and can cause crashes, and the types of activities reported
are varied. Increased driver awareness of the adverse consequences of distracted
driving with a focus on novice drivers, enforcement of existing laws (e.g. those
requiring a driver to maintain proper control of a vehicle), and progress on
engineering initiatives (such as collision warning systems) are needed to reduce
injury.
PMID- 17034749
TI - Mobile phone use while driving in a sample of Spanish university workers.
AB - A number of epidemiological studies have reported drivers who use a mobile phone
while driving have an elevated risk of being involved in a crash. This is
particularly concerning as a survey of drivers in the Spanish region of Catalunya
found that approximately 87% own mobile phones. The present study investigated
the reported frequency of mobile phone use on Spanish roads (for talking and
using SMS), the characteristics of the drivers who use mobile phones while
driving and whether they altered their driving behaviour when using a mobile
phone. The research found that more than 60% use a mobile phone while driving and
that the phone is mostly used for making calls, rather than using SMS. In
general, males and females use mobile phones about the same reported frequency,
although males were more likely to use a mobile phone to talk on the highway. The
pattern for age was the same for both male and female participants, with the
younger drivers using SMS more frequently than older drivers. On urban roads
almost half of the drivers reported changing their driving behaviour when using a
mobile phone, while on the highway this figure was slightly over 41%. The
reported frequency of using a mobile phone to talk on urban roads was
significantly correlated with crash involvement. However, this affect disappeared
once the contributions of the demographic and descriptive variables had been
partialled out.
PMID- 17034750
TI - Magazine information on safety belt use for pregnant women and young children.
AB - To assess the information on safety belt use for pregnant women and infants in
maternity and baby magazines, we reviewed 2003 issues of the three top-selling
monthly baby and maternity magazines. Articles on safety belt use during
pregnancy and child safety seat (CSS) use for infants, and advertisements of the
CSS, automobiles, or CSS-related products were examined for their informational
content. Of the 9418 pages in the maternity magazines, 46 pages were on infants,
16 pages on pregnant women and 162 pages displayed advertisements. Of the 9750
pages in the baby magazines, 34 pages of articles addressed CSS use; no articles
addressed the issue of pregnant women; 83 pages were advertisements. Although the
magazines showed accurate information in general; its amount was not sufficient,
and little specific information on appropriate use and selection of a CSS was
seen. Some information was misleading and even incorrect: specifically related to
when to start using a forward-facing seat, what products are attachable to the
CSS, and the reuse of a CSS. Greater amounts and accuracy of safety information
in these magazines would help pregnant women and parents acquire important safety
knowledge that healthcare providers are falling short of providing in Japan.
PMID- 17034751
TI - Protein array staining methods for undefined protein content, manufacturing
quality control, and performance validation.
AB - Methods to assess the quality and performance of protein microarrays fabricated
from undefined protein content are required to elucidate slide-to-slide
variability and interpolate resulting signal intensity values after an
interaction assay. We therefore developed several simple total- and
posttranslational modification-specific, on-chip staining methods to
quantitatively assess the quality of gel element protein arrays manufactured with
whole-cell lysate in vitro protein fractions derived from two-dimensional liquid
phase fractionation (PF2D) technology. A linear dynamic range of at least 3 logs
was observed for protein stains and immobilized protein content, with a lower
limit of detection at 8 pg of protein per gel element with Deep Purple protein
stain and a field-portable microarray imager. Data demonstrate the successful
isolation, separation, transfer, and immobilization of putative transmembrane
proteins from Yersinia pestis KIM D27 with the combined PF2D and gel element
array method. Internal bovine serum albumin standard curves provided a method to
assess on-chip PF2D transfer and quantify total protein immobilized per gel
element. The basic PF2D array fabrication and quality assurance/quality control
methods described here therefore provide a standard operating procedure and basis
for developing whole-proteome arrays for interrogating host-pathogen
interactions, independent of sequenced genomes, affinity tags, or a priori
knowledge of target cell composition.
PMID- 17034752
TI - Single DNA molecule stretching measures the activity of chemicals that target the
HIV-1 nucleocapsid protein.
AB - We develop a biophysical method for investigating chemical compounds that target
the nucleic acid chaperone activity of HIV-1 nucleocapsid protein (NCp7). We used
an optical tweezers instrument to stretch single lambda-DNA molecules through the
helix-coil transition in the presence of NCp7 and various chemical compounds. The
change in the helix-coil transition width induced by wild-type NCp7 and its zinc
finger variants correlates with in vitro nucleic acid chaperone activity
measurements and in vivo assays. The compound-NC interaction measured here
reduces NCp7's capability to alter the transition width. Purified compounds from
the NCI Diversity set, 119889, 119911, and 119913 reduce the chaperone activity
of 5 nM NC in aqueous solution at 10, 25, and 100 nM concentrations respectively.
Similarly, gallein reduced the activity of 4 nM NC at 100 nM concentration.
Further analysis allows us to dissect the impact of each compound on both
sequence-specific and non-sequence-specific DNA binding of NC, two of the main
components of NC's nucleic acid chaperone activity. These results suggest that
DNA stretching experiments can be used to screen chemical compounds targeting NC
proteins and to further explore the mechanisms by which these compounds interact
with NC and alter its nucleic acid chaperone activity.
PMID- 17034753
TI - Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human
bronchioepithelial cells.
AB - High dose beta-carotene supplementation of smokers was associated with increased
lung cancer risk in two intervention trials. It was proposed that generation of
apocarotenals in smoke-exposed lungs impaired retinoic acid (RA) signaling,
leading to squamous metaplasia and cell proliferation. To test this, we compared
RA target gene regulation by retinoids, apocarotenals or beta-carotene by
transcriptomics in BEAS-2B cells cultured to promote squamous differentiation.
Retinoids, beta-carotene as well as apocarotenals induced known RA target genes.
Retinoids upregulated involucrin, indicating that retinoids did not rescue BEAS
2B cells from squamous differentiation. Muc5AC, a marker for mucous
differentiation, was transiently induced. beta-Carotene and apocarotenals less
strongly induced involucrin and did not induce muc5AC. In summary, apocarotenals
or beta-carotene upregulated RA target genes suggesting promotion, not
inhibition, of RA signaling in BEAS-2B cells. Furthermore, apocarotenals and beta
carotene regulated gene expression independently of RA signaling. Squamous
differentiation is not unequivocally linked to RA deficiency in BEAS-2B cells.
PMID- 17034754
TI - Acclimation of mesophyll and bundle sheath chloroplasts of maize to different
irradiances during growth.
AB - The regulation by light of the photosynthetic apparatus, and composition of light
harvesting complexes in mesophyll and bundle sheath chloroplasts was investigated
in maize. Leaf chlorophyll content, level of plastoquinone, PSI and PSII
activities and Lhc polypeptide compositions were determined in plants grown under
high, moderate and low irradiances. Photochemical efficiency of PSII,
photochemical fluorescence quenching and non-photochemical fluorescence quenching
over a range of actinic irradiances were also determined, using chlorophyll a
fluorescence analysis. Acclimation of plants to different light conditions caused
marked changes in light-harvesting complexes, LHCI and LHCII, and antenna
complexes were also reorganized in these types of chloroplasts. The level of
LHCII increased in plants grown in low light, even in agranal bundle sheath
chloroplasts where the amount of PSII was strongly reduced. Irradiance also
affected LHCI complex and the number of structural polypeptides, in this complex,
generally decreased in chloroplasts from plants grown under lower light.
Surprisingly moderate and low irradiances during growth do not affect the light
reaction and fluorescence parameters of plants but generated differences in
composition of light-harvesting complexes in chloroplasts. On the other hand, the
changes in photosynthetic apparatus in plants acclimated to high light, resulted
in a higher efficiency of photosynthesis. Based on these observations we propose
that light acclimation to high light in maize is tightly coordinated adjustment
of light reaction components/activity in both mesophyll and bundle sheath
chloroplasts. Acclimation is concerned with balancing light utilization and level
of the content of LHC complexes differently in both types of chloroplasts.
PMID- 17034755
TI - Spatial and temporal Ca2+, Mg2+, and ATP2- dynamics in cardiac dyads during
calcium release.
AB - We have constructed a three-dimensional reaction-diffusion model of the mammalian
cardiac calcium release unit. We analyzed effects of diffusion coefficients,
single channel current amplitude, density of RyR channels, and reaction kinetics
of ATP(2-) with Ca(2+) and Mg(2+) ions on spatiotemporal concentration profiles
of Ca(2+), Mg(2+), and ATP(2-) in the dyadic cleft during Ca(2+) release. The
model revealed that Ca(2+) concentration gradients persist near RyRs in the
steady state. Even with low number of open RyRs, peak [Ca(2+)] in the dyadic
space reached values similar to estimates of luminal [Ca(2+)] in approximately 1
ms, suggesting that during calcium release the Ca(2+) gradient moves from the
cisternal membrane towards the boundary of the dyadic space with the cytosol. The
released Ca(2+) bound to ATP(2-), and thus substantially decreased ATP(2-)
concentration in the dyadic space. The released Ca(2+) could also replace Mg(2+)
in its complex with ATP(2-) during first milliseconds of release if dissociation
of MgATP was fast. The results suggest that concentration changes of Ca(2+),
Mg(2+), and ATP(2-) might be large and fast enough to reduce dyadic RyR activity.
Thus, under physiological conditions, termination of calcium release may be
facilitated by the synergic effect of the construction and chemistry of mammalian
cardiac dyads.
PMID- 17034756
TI - Coexistence of two domains in intercellular lipid matrix of stratum corneum.
AB - The outermost layer of the skin, the stratum corneum (SC), is composed of
corneocytes and an intercellular lipid matrix. The matrix acts as both the main
barrier and also as the pathway of water, drugs, etc. across the SC. In the
mammalian SC, the longitudinal arrangement of the lipid molecules, consisting of
long and short lamellar structures with repeat distances of about 13 nm and 6 nm,
respectively, has been observed by small-angle X-ray diffraction. In the lateral
arrangement of the lipid molecules, hexagonal and orthorhombic hydrocarbon-chain
packing has been observed by wide-angle X-ray diffraction. From the systematic
study of the temperature dependence of simultaneous small- and wide-angle X-ray
diffraction patterns, we demonstrate that the intercellular lipid matrix forms
two domains, which consist at room temperature of a long lamellar structure with
hexagonal hydrocarbon-chain packing and a short lamellar structure with
orthorhombic hydrocarbon-chain packing.
PMID- 17034757
TI - Molecular interaction between fukutin and POMGnT1 in the glycosylation pathway of
alpha-dystroglycan.
AB - The recent identification of mutations in genes encoding demonstrated or putative
glycosyltransferases has revealed a novel mechanism for congenital muscular
dystrophy. Hypoglycosylated alpha-dystroglycan (alpha-DG) is commonly seen in
Fukuyama-type congenital muscular dystrophy (FCMD), muscle-eye-brain disease
(MEB), Walker-Warburg syndrome (WWS), and Large(myd) mice. POMGnT1 and POMTs, the
gene products responsible for MEB and WWS, respectively, synthesize unique O
mannose sugar chains on alpha-DG. The function of fukutin, the gene product
responsible for FCMD, remains undetermined. Here we show that fukutin co
localizes with POMGnT1 in the Golgi apparatus. Direct interaction between fukutin
and POMGnT1 was confirmed by co-immunoprecipitation and two-hybrid analyses. The
transmembrane region of fukutin mediates its localization to the Golgi and
participates in the interaction with POMGnT1. Y371C, a missense mutation found in
FCMD, retains fukutin in the ER and also redirects POMGnT1 to the ER. Finally, we
demonstrate reduced POMGnT1 enzymatic activity in transgenic knock-in mice
carrying the retrotransposal insertion in the fukutin gene, the prevalent
mutation in FCMD. From these findings, we propose that fukutin forms a complex
with POMGnT1 and may modulate its enzymatic activity.
PMID- 17034758
TI - A novel phytase with preferable characteristics from Yersinia intermedia.
AB - A Yersinia intermedia strain producing phytase was isolated from glacier soil.
The phytase gene, appA, was isolated by degenerate PCR and TAIL-PCR. The full
length fragment contained 2354bp with a 1326-bp open reading frame encoding 441
amino acids. APPA contained the active site RHGXRXP and HD sequence motifs that
are typical of histidine acid phosphatases. To our knowledge, this is the first
report of the detection of phytase activity and cloning of the relevant gene from
Y. intermedia. The gene was overexpressed in Pichia pastoris, and the purified
recombinant APPA had a specific activity for sodium phytate of 3960U/mg, which is
higher than that of the Citrobacter braakii phytase (previously the highest
specific activity known). Recombinant APPA had high activity from pH 2 to 6
(optimum 4.5) and optimal temperature of 55 degrees C; the enzyme was resistant
to pepsin and trypsin. These characteristics suggest that APPA may be highly
suitable for use in the feed industry.
PMID- 17034759
TI - Oxidative stress-induced intestinal epithelial cell apoptosis is mediated by p38
MAPK.
AB - Free oxygen radicals are involved in the pathogenesis of necrotizing
enterocolitis (NEC) in premature infants. The stress-activated p38 mitogen
activated protein kinase (MAPK) has been implicated in gut injury. Here, we found
that phosphorylated p38 was detected primarily in the villus tips of normal
intestine, whereas it was expressed in the entire mucosa in NEC. H(2)O(2)
treatment resulted in a rapid phosphorylation of p38 MAPK and subsequent
apoptosis of rat intestinal epithelial (RIE)-1 cells; this induction was
attenuated by treatment with SB203580, a selective p38 MAPK inhibitor, or
transfection with p38alpha siRNA. Moreover, SB203580 also blocked H(2)O(2)
induced PKC activation. In contrast, the PKC inhibitor (GF109203x) did not affect
p38 activation, indicating that p38 MAPK activation occurs upstream of PKC
activation in H(2)O(2)-induced apoptosis. H(2)O(2) treatment also decreased
mitochondrial membrane potential; pretreatment with SB203580 attenuated this
response. Our study demonstrates that the p38 MAPK/PKC pathway plays an important
role as a pro-apoptotic cellular signaling during oxidative stress-induced
intestinal epithelial cell injury.
PMID- 17034760
TI - A threonine synthase homolog from a mammalian genome.
AB - The genomes of several vertebrates contain two genes encoding proteins highly
similar to threonine synthase (TS), even though the biosynthesis of l-threonine
(l-Thr) is not known to occur in these animals. We report a bioinformatic
analysis of the two TS-like genes, the recombinant expression of one murine TS
homolog (mTSH2) and its initial biochemical characterization. Recombinant mTSH2
contained bound pyridoxal-5'-phosphate (PLP), but did not synthesize l-Thr. The
enzyme did, however, bind O-phospho-homoserine (PHS; the actual TS substrate) and
degraded it to alpha-ketobutyrate, phosphate, and ammonia-a known side reaction
of microbial TSs. mTSH2 also degraded O-phospho-threonine (PThr) to alpha
ketobutyrate, showing that it can act as a catabolic phospho-lyase on both gamma-
and beta-phosphorylated substrates. These findings suggest an unusual
evolutionary origin for mTSH2, whereby an original TS enzyme became 'recycled'
into a phospho-lyase upon dismissal, in metazoa, of the l-Thr biosynthetic
pathway.
PMID- 17034762
TI - Amiloride attenuates glycine-induced currents in cultured neurons of rat inferior
colliculus.
AB - Amiloride, a potassium sparing diuretic, is well known to interact with many ion
transport systems and modulate the activity of several membrane receptors.
However, relatively little information is available as to how amiloride affects
membrane receptors of neurons in the brain areas. In the present study, we
investigated the effects of amiloride on glycine-induced currents (I(Gly)) in
cultured neurons of rat inferior colliculus with whole-cell patch-clamp
recordings. Amiloride itself did not activate any current across the neuronal
membrane but it reversibly inhibited the amplitude of the I(Gly) in a reversible
and concentration-dependent manner, with an IC(50) of 487.4+/-25.3microM (n=5).
Amiloride shifted the concentration-response relationship to the right without
changing Hill coefficient and without changing the maximum response of the
I(Gly). The pre-perfusion of amiloride produced an inhibitory effect on the
I(Gly). In addition, amiloride was shown with a voltage ramp protocol to
significantly reduce the conductance induced by glycine but not to change the
reversal potential of the I(Gly). These results demonstrate that amiloride
competitively inhibits the I(Gly) in rat inferior colliculus neurons by
decreasing the affinity of glycine to its receptor. Our finding suggests that
attention should be paid to the possible side effects of amiloride used as a drug
on brain functions in the case of a defective blood-brain barrier and in the case
of direct application of this drug into the cerebrospinal fluid for treatment of
brain tumors.
PMID- 17034761
TI - Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced
homodimerization of TLR4.
AB - Toll-like receptors (TLRs), which are activated by invading microorganisms or
endogenous molecules, evoke immune and inflammatory responses. TLR activation is
closely linked to the development of many chronic inflammatory diseases including
rheumatoid arthritis. Auranofin, an Au(I) compound, is a well-known and long-used
anti-rheumatic drug. However, the mechanism as to how auranofin relieves the
symptom of rheumatoid arthritis has not been fully clarified. Our results
demonstrated that auranofin suppressed TLR4-mediated activation of transcription
factors, NF-kappaB and IRF3, and expression of COX-2, a pro-inflammatory enzyme.
This suppression was well correlated with the inhibitory effect of auranofin on
the homodimerization of TLR4 induced by an agonist. Furthermore, auranofin
inhibited NF-kappaB activation induced by MyD88-dependent downstream signaling
components of TLR4, MyD88, IKKbeta, and p65. IRF3 activation induced by MyD88
independent signaling components, TRIF and TBK1, was also downregulated by
auranofin. Our results first demonstrate that auranofin suppresses the multiple
steps in TLR4 signaling, especially the homodimerization of TLR4. The results
suggest that the suppression of TLR4 activity by auranofin may be the molecular
mechanism through which auranofin exerts anti-rheumatic activity.
PMID- 17034763
TI - Transcriptional targeting of small interfering RNAs into cancer cells.
AB - Small interfering RNAs (siRNAs) are widely used for analyzing gene function and
have the potential to be developed into human therapeutics. However, persistent
siRNA expression in normal cells may cause toxic side effects. Therefore, the
therapeutic applications of RNAi in cancer require either the specific delivery
of synthetic siRNAs into cancer cells or the control of siRNA expression.
Accordingly, we have developed a cancer-specific vector that expresses siRNAs
from the human survivin promoter. A plasmid vector expressing siRNAs under this
promoter enabled efficient gene silencing of gene expression in different cancer
cell lines. The levels of inhibition were comparable to that obtained with the
constitutively active U6 promoter. By contrast to U6 promoter, no significant
gene silencing was obtained with the Survivin promoter in normal mammary
epithelial cells. Collectively, these data indicate that the survivin promoter is
suitable for directing siRNA expression in cancer cells, but not normal cells.
PMID- 17034764
TI - Identification of two biologically crucial hydroxyl groups of (-)
epigallocatechin gallate in osteoclast culture.
AB - (-)-Epigallocatechin gallate (EGCG) induces cell death of osteoclasts in an
Fe(2+)- and H(2)O(2)-dependent manner. In the present study, we further explore
the cytotoxic mechanism of EGCG using four EGCG analogues. Molecules methylated
at position 4' in the B ring (EGCG-4'-O-Me) or at position 4'' in the D-ring
(EGCG-4''-O-Me) showed markedly decreased cytotoxicity to osteoclasts, indicating
that hydroxyl groups at these two positions of EGCG are crucial for inducing cell
death of osteoclasts. EGCG-4'-O-Me also showed the lowest Fe(3+)-reducing
activity among five EGCGs. The Fe(3+)-reducing activity of EGCG was enhanced
under conditions whereby protonated EGCG levels were increased, indicating that
the protonated status of EGCG was involved in the Fe(3+)-reducing activity. The
hydroxyl group at position 4'' in the D-ring was shown by quantum chemical
calculation to be preferentially deprotonated among all of the hydroxyl groups in
EGCGs. It was also shown that the highest occupied molecular orbital (HOMO) was
localized to the B-ring of EGCGs, except for EGCG-4'-O-Me. We report here that
the HOMO on the B-ring plays crucial roles in both the Fe(3+)-reducing activity
of EGCG and the cytotoxicity of EGCG to osteoclasts, while deprotonation of the
hydroxyl group at position 4'' in the D-ring plays a supplementary role.
PMID- 17034765
TI - "Non-serotonergic" lateral superior olivary neurons of the neonatal mouse contain
serotonin.
AB - In mutant mice which have high serotonin (5-HT) levels perinatally, neurons in
the lateral superior olive (LSO, which are not serotonergic), contain 5-HT
transiently in the neonatal period of development. We determined that the same
phenomenon occurs in non-genetically altered mice: LSO neurons were 5-HT
immunoreactive at postnatal days 1 and 8. These findings suggest accumulation of
5-HT in by LSO neurons during postnatal development.
PMID- 17034767
TI - Effect of gravity on human spontaneous 10-Hz electroencephalographic oscillations
during the arrest reaction.
AB - Electroencephalographic oscillations at 10 Hz (alpha and mu rhythms) are the most
prominent rhythms observed in awake, relaxed (eye-closed) subjects. These
oscillations may be considered as a marker of cortical inactivity or an index of
the active inhibition of the sensory information. Different cortical sources may
participate in the 10-Hz oscillation and appear to be modulated by the sensory
context and functional demands. In microgravity, the marked reduction in
multimodal graviceptive inputs to cortical networks participating in the
representation of space could be expected to affect the 10-Hz activity. The
effect of microgravity on this basic oscillation has heretofore not been studied
quantitatively. Because the alpha rhythm has a functional role in the regulation
of network properties of the visual areas, we hypothesised that the absence of
gravity would affect its strength. Here, we report the results of an experiment
conducted over the course of 3 space flights, in which we quantified the power of
the 10-Hz activity in relation to the arrest reaction (i.e., in 2 distinct
physiological states: eyes open and eyes closed). We observed that the power of
the spontaneous 10-Hz oscillation recorded in the eyes-closed state in the
parieto-occipital (alpha rhythm) and sensorimotor areas (mu rhythm) increased in
the absence of gravity. The suppression coefficient during the arrest reaction
and the related spectral perturbations produced by eye-opening/closure state
transition also increased in on orbit. These results are discussed in terms of
current theories on the source and the importance of the alpha rhythm for
cognitive function.
PMID- 17034766
TI - Proteomic analysis of the effects of cocaine on the enhancement of HIV-1
replication in normal human astrocytes (NHA).
AB - The US is experiencing an epidemic of cocaine use entangled with HIV-1 infection.
Normal human astrocytes (NHA) are susceptible to HIV-1 infection. We utilized LTR
R/U5 amplification, p24 antigen assay and the proteomic method of difference gel
electrophoresis (DIGE) combined with protein identification through HPLC-MS/MS to
investigate the effect of cocaine on HIV-1 infectivity and the proteomic profile
of NHA, respectively. Data demonstrate that cocaine significantly upregulates HIV
1 infection in NHA as measured by LTR-R/U5 amplification and p24 antigen assay.
Further, our results show for the first time that cocaine differentially
regulates the expression of a number of proteins by NHA that may play a role in
the neuropathogenesis of HIV-1 disease.
PMID- 17034768
TI - An ERP investigation of emotional processing in European and Japanese
individuals.
AB - This article examined neural time course differences in the processing of
emotional pictures in European and Asian individuals. Event-related potentials
(ERPs) were recorded in 15 French and 15 Japanese volunteers during the
presentation of neutral and emotional pictures in their own country. ERPs were
analyzed by means of spatio-temporal Principal Component Analysis (PCA) and allow
to evaluate cultural influences on emotional processing along three temporal
windows: 105 to 140 ms, 176 to 230 ms and 255 to 455 ms. Main results highlight
that (1) early ERP components coded emotional charge but were not modulated by
cultural background, (2) later components showed a significant decrease of
amplitudes at parieto-occipital areas for Japanese participants compared to
French ones in emotional condition. These findings suggest that, in both
populations, similar neurocognitive processes are involved in the early stage of
the emotional stimuli processing and effects observed on later components may
reflect a poorer engagement of parietal areas, known to be involved in emotional
arousal dimension. Considering that cognitive judgments were similar in both
populations, electrophysiological findings suggest that cultural influences on
later stage of emotional processing could be related to the known lower level of
emotionally expressive behavior in Japanese than in Caucasians.
PMID- 17034769
TI - PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes.
AB - 5-aminolevulinic acid (ALA) and carnosine have important physiological and
pathophysiological roles in the CNS. Both are substrates for the proton-coupled
oligopeptide transporter PEPT2. The purpose of the current study was to determine
the importance of PEPT2 in the uptake of ALA and carnosine in rat and mouse
(PEPT2+/+ and PEPT2-/-) cultured neonatal astrocytes. Although neonatal
astrocytes are known to express PEPT2, its quantitative importance in the
transport of these compounds is not known. [14C]ALA uptake in neonatal rat
astrocytes was inhibited by dipeptides, an alpha-amino containing cephalosporin
(which is a PEPT2 substrate) but was not affected by a non-amino containing
cephalosporin (which is not a PEPT2 substrate). Uptake was pH sensitive as
expected from a proton-coupled transporter and was saturable (Vmax=715+/-29
pmol/mg/min, Km=606+/-14 microM). [3H]Carnosine uptake in neonatal rat astrocytes
was inhibited by dipeptides but not by histidine (a substrate for the
peptide/histidine transporters PHT1 and PHT2) and also showed saturable transport
(Vmax=447+/-23 pmol/mg/min, Km=43+/-5.5 microM). Neonatal astrocytes from PEPT2-/
mice had a 62% reduction in [14C]ALA uptake and a 92% reduction in [3H]carnosine
uptake compared to PEPT2+/+ mice. These results demonstrate that PEPT2 is the
primary transporter responsible for the astrocytic uptake of ALA and carnosine.
PMID- 17034770
TI - Cyclomaltooligosaccharide-assisted spectroscopic discrimination of phthalimido
derived amino acids through the formation of molecular aggregates.
AB - Spectroscopic evidence was used to demonstrate the formation of molecular
associates in an aqueous solution of phthalimido tryptophan. These molecular
associates are loosely formed through pi-pi aromatic stacking, properties that
are not sufficient to cause NMR spectroscopic enantiomeric discrimination. A
cyclomaltooligosaccharide with a larger cavity, such as cyclomaltooctaose (gamma
cyclodextrin), is capable of forming a ternary complex with these molecular
associates and enhances pi-pi aromatic stacking interactions, resulting in NMR
enantiomeric discrimination. Electrospray-ionization mass spectroscopy (ESIMS)
and NOESY two-dimensional NMR spectroscopic methods were used to study these
complexes. Association constants and thermodynamic data for these
cyclomaltooligosaccharide complexes were also estimated.
PMID- 17034771
TI - Fatty acid transporter levels and palmitate oxidation rate correlate with
ejection fraction in the infarcted rat heart.
AB - OBJECTIVES: Cardiac fatty acid uptake occurs predominantly via sarcolemmal
transporter proteins; fatty acid translocase (FAT/CD36), plasma membrane fatty
acid binding protein (FABPpm) and fatty acid transporter proteins (FATP) 1 and 6.
We hypothesised that levels of the fatty acid transporters would be reduced in
the chronically infarcted rat heart, in parallel with reduced dependence on fatty
acid utilisation. METHODS AND RESULTS: In vivo left ventricular ejection
fractions, measured using echocardiography, were 36% lower in rats six months
after coronary artery ligation than in sham-operated control rats. In isolated,
perfused, infarcted hearts, 3H-palmitate oxidation was 30% lower, and correlated
with in vivo ejection fractions. As myocardial lipid incorporation was also
reduced by 25%, total palmitate utilisation was 29% lower in the infarcted rat
heart. The protein levels of the cardiac fatty acid transporters were reduced in
the infarcted rat heart; FAT/CD36 by 36%, FABPpm by 12%, FATP6 by 21% and FATP1
by 26%, and the cytosolic fatty acid binding protein (cFABP) was 47% lower than
in sham-operated rat hearts. Fatty acid transporter levels correlated with both
palmitate oxidation rates and cardiac ejection fractions. CONCLUSIONS: Reductions
in fatty acid oxidation and lipid incorporation rates were accompanied by
downregulation of the cardiac fatty acid transporters. The metabolic shift away
from fatty acid utilisation was proportional to the degree of functional
impairment in the chronically infarcted rat heart.
PMID- 17034772
TI - Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic
heart failure.
AB - Chronic heart failure is a complex catabolic state that carries a devastating
prognosis. The transition from stable disease to cardiac cachexia is not well
understood. Mechanisms that maintain the wasting process involve neurohormones
and pro-inflammatory cytokines, which contribute to an imbalance in anabolic and
catabolic pathways. A decrease in food intake alone rarely triggers the
development of a wasting process, but dietary deficiencies in micronutrients and
macronutrients contribute to the progression of the disease. Malabsorption from
the gut as a result of bowel wall edema and decreased bowel perfusion also plays
an important role. This article describes the complex interplay of hormonal
systems in energy balance in patients with chronic heart failure as well as other
factors such as malabsorption and dietary deficiencies that contribute to the
wasting process. Finally, therapeutic approaches are discussed. These include
dietary advice, ongoing studies, and future possibilities.
PMID- 17034773
TI - Phosphodiesterase 7A1 is expressed in human CD4+ naive T cells at higher levels
than in CD4+ memory cells and is not required during their CD3/CD28-dependent
activation.
AB - PDE7A1 is a cAMP-hydrolyzing phosphodiesterase expressed in lymphoid tissue,
where its possible role during T cell activation remains unclear. We have
characterized the functional relevance of PDE7A1 in the naive (CD4+CD45RA+) and
memory (CD4+CD45RO+) subsets of human peripheral CD4+ T cells during CD3/CD28
dependent stimulation. Our results indicate that PDE7A1 is expressed in resting
naive CD4+ T cells at higher levels than in the corresponding memory cells and
that levels of PDE7A1 mRNA are not upregulated upon CD3/CD28 mediated stimulation
of these T cell subsets. Treatment with a selective inhibitor of PDE7A1 does not
impair CD3/CD28 induced activation of naive or memory CD4+ T cells, nor does it
increase intracellular cAMP in CD4+ T cells. We conclude that PDE7A1 is not
required during CD3/CD28-dependent activation of naive and memory CD4+ T cells,
but cannot rule out other regulatory roles of PDE7A1 during maturation of CD4+ T
cells.
PMID- 17034774
TI - Lactoferrin activates macrophages via TLR4-dependent and -independent signaling
pathways.
AB - Lactoferrin (LF) is a component of innate immunity and is known to interact with
accessory molecules involved in the TLR4 pathway, including CD14 and LPS binding
protein, suggesting that LF may activate components of the TLR4 pathway. In the
present study, we have asked whether bovine LF (bLF)-induced macrophage
activation is TLR4-dependent. Both bLF and LPS stimulated IL-6 production and
CD40 expression in RAW 264.7 macrophages and in BALB/cJ peritoneal exudate
macrophages. However, in macrophages from congenic TLR4(-/-) C.C3-Tlr4(lps-d)
mice, CD40 was not expressed while IL-6 secretion was increased relative to wild
type cells. The signaling components NF-kappaB, p38, ERK and JNK were activated
in RAW 264.7 cells and BALB/cJ macrophages after bLF or LPS stimulation,
demonstrating that the TLR4-dependent bLF activation pathway utilizes signaling
components common to LPS activation. In TLR4 deficient macrophages, bLF-induced
activation of NF-kappaB, p38, ERK and JNK whereas LPS-induced cell signaling was
absent. We conclude from these studies that bLF induces limited and defined
macrophage activation and cell signaling events via TLR4-dependent and
independent mechanisms. bLF-induced CD40 expression was TLR4-dependent whereas
bLF-induced IL-6 secretion was TLR4-independent, indicating potentially separate
pathways for bLF mediated macrophage activation events in innate immunity.
PMID- 17034775
TI - Antiangiogenic effect of Lygodium flexuosum against N-nitrosodiethylamine-induced
hepatotoxicity in rats.
AB - The antiangiogenic effect of Lygodium flexuosum extract was evaluated in Wistar
rats intoxicated with N-nitrosodiethylamine (NDEA) in preventive and curative
models. In preventive groups, NDEA was administered for 20 weeks. Daily doses of
L. flexuosumn-hexane extract (200mg/kg) started 1 week before the onset of NDEA
intoxication and continued for 20 weeks. In curative animals, NDEA was
administered for 20 weeks followed by treatment with the n-hexane extract of L.
flexuosum for 28 days. Rats intoxicated with NDEA had elevated levels of serum
gamma-GT, AST, ALT, LDH levels and hepatic MDA and decreased levels of hepatic
GSH. When treated with L. flexuosum extract had normal levels of gamma-GT, AST,
ALT, LDH levels, hepatic MDA and GSH. NDEA administered rat liver showed an
overexpressed levels of angiopoietins 1 (Ang-1) and 2 (Ang-2) and its receptor
Tie-2 mRNA. L. flexuosum extract treatment significantly (p680ppm (odds ratio (OR)=3.37, 95% confidence interval (CI)=1.20
9.46). The effect was significant at the middle tertile TVOCs level of 114-360ppb
(OR=2.62, 95% CI=1.43-4.79), but not at the highest tertile. Inadequate
ventilation in office increases the risk of building-related oxidative stress in
non-smoking employees.
PMID- 17034785
TI - Absorption of folate by Caco-2 cells is not affected by high glucose
concentration.
AB - The aim of this work was to investigate the effect of high glucose exposure on
the absorption of folate by Caco-2 cells. We verified that apical high glucose
did not affect the apical uptake of [(3)H]folate. Both different concentrations
of glucose (10-45 mM) and different exposure times (10 min-24 h) were tested.
Furthermore, apical high glucose (30 mM) did not affect the intracellular steady
state levels of [(3)H]folate, and simultaneous apical and basolateral high
glucose (30 mM) did not change the apical-to-basolateral apparent permeability
(P(app)) to [(3)H]folate. Both the apical uptake and the steady-state
intracellular levels of [(3)H]folate were strongly reduced by 5
methyltetrahydrofolate, methotrexate, SITS (4-acetamido-4'-isothiocyanato-2,2'
stilbenedisulfonic acid), DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic
acid) and indomethacin, but were not affected or only hardly affected by p
aminohippuric acid and fumitremorgin C. Moreover, DIDS and indomethacin
significantly reduced (by 50-60%) the apical-to-basolateral P(app) to
[(3)H]folate, but [(3)H]folate present in the cells at the end of the experiment
was higher in the case of indomethacin. Fumitremorgin C had no effect. The effect
of the drugs tested was not changed or only hardly changed by high glucose. In
conclusion, absorption of [(3)H]folate is not modulated by either apical or
basolateral high glucose exposure in Caco-2 cells. Moreover, our results suggest
that the apical uptake of [(3)H]folate by Caco-2 cells involves the Reduced
Folate Transporter (but not the Organic Anion Transporter), and that Multidrug
Resistance Protein and/or Organic Anion Transporter (but not Breast Cancer
Resistance Protein) may mediate apical efflux of [(3)H]folate.
PMID- 17034786
TI - Baclofen and potential therapeutic use: studies of neuronal survival.
AB - Up to now, baclofen (a GABA(B) receptor agonist) has been used for the treatment
of severe spasticity unresponsive to oral antispasmodics. Although in humans it
is usually administered at 2 mg/ml, the dosage to be used in the treatment of
other diseases is unknown. For this reason, it is important to determine the safe
maximum dosage and toxicity at the clinically used concentration. Primary
cortical neurons represent a useful model to test the safety of baclofen. We
performed a colorimetric assay (MTT test) as well as electron microscopy
investigations, to determine neuronal survival after the treatment with baclofen
at a concentration of 2 and 4 mg/ml. Our results demonstrated that, in our
experimental model, neither concentration affected neuronal survival. Considering
the above results, we can conclude that at the used concentrations, this drug is
safe and its clinical use should be encouraged.
PMID- 17034787
TI - The selective effect of cystathionine on doxorubicin hepatotoxicity in tumor
bearing mice.
AB - The aim of the present study was to examine the protective effect of
cystathionine as a cysteine precursor on doxorubicin toxicity in the liver of
Ehrlich ascites tumor (EAT)-bearing mice and in the EAT cells. Both compounds
were injected intraperitoneally alone or in combination at the following doses:
cystathionine at 10 mg and doxorubicin at 5 mg per kg of body weight. In the
liver of EAT-bearing mice, glutathione (GSH), cysteine and sulfane sulfur levels
as well as the activities of: glutathione S-transferase, gamma-glutamyl
transpeptidase, rhodanese and gamma-cystathionase significantly dropped in
comparison with healthy animals. Administration of cystathionine elevated GSH and
cysteine levels in the livers of EAT-bearing mice and reduced lipid peroxidation.
Furthermore, cystathionine increased gamma-glutamyl transpeptidase activity,
thereby activating gamma-glutamyl cycle, responsible for proper glutathione
metabolism in the cells. Cystationine did not influence sulfane sulfur level and
rhodanese and gamma-cystathionase activity in the livers of EAT-bearing mice. It
was next shown that cystathionine administered in combination with doxorubicin
protected against the drug toxicity since it elevated thiol level, lowering
reactive oxygen species content and suppressing lipid peroxidation. This means
that, cystathionine in the liver of EAT-bearing mice can both correct harmful
effects of carcinogenesis, and protect the liver from doxorubicin cytotoxicity.
In contrast, in EAT cells, cystathionine lowered GSH and cysteine levels and did
not alter reactive oxygen species level, lipid peroxidation, and gamma-glutamyl
transpeptidase activity. All these data indicate that cystathionine action is
selectively beneficial for normal cells because it corrects harmful effects
induced by EAT development and protects the organism against doxorubicin
cytotoxicity without impairing cytotoxicity of this drug to tumor cells.
PMID- 17034788
TI - CYP2E1 induced by ethanol causes oxidative stress, proteasome inhibition and
cytokeratin aggresome (Mallory body-like) formation.
AB - The role of oxidative stress in alcoholic liver disease and cytokeratin aggresome
formation is the focus of this in vitro study. HepG2 cells transduced to over
express CYP2E1 (E47) and control HepG2 cells (C34) were first treated with
arachidonic acid, then Fe-NAT, and finally with ethanol. In the E47 ethanol
treated cells, CYP2E1 was induced and a higher level of reactive oxygen species
and carbonyl proteins were generated. The proteasome activity decreased
significantly in the E47 ethanol-treated cells. This inhibition was prevented
when CYP2E1 was inhibited by DAS. Microarray analysis showed gene expression down
regulation of the proteasome subunit, as well as ubiquitin pathway proteins in
the E47 ethanol-treated cells. 4-Hydroxynonenal (4-HNE) adducts were increased in
the E47 cells treated with ethanol. Furthermore, the immunoprecipitated 4-HNE
modified proteins from these cells stained positive with antibodies to the
proteasome subunit alpha 6. These results indicate that the ethanol induced
CYP2E1 generates oxidative stress that is responsible for the decrease in
proteasome activity. Cytokeratin 8 and 18 were induced by ethanol treatment of
E47 cells and polyubiquitinated forms of these proteins were found in the
polyubiquitin smear upon Western blots analysis. Cytokeratin aggresomes and
Mallory body-like inclusions formed in the ethanol-treated E47 cells, indicating
that the ubiquitinated cytokeratins accumulated as a result of the inhibition of
the proteasome by ethanol treatment when oxidation of ethanol induced oxidative
stress. This is the first report where ethanol caused Mallory body-like
cytokeratin inclusions in transformed human liver cells in vitro.
PMID- 17034789
TI - Alpha-complementation as a probe for dual localization of mitochondrial proteins.
AB - There are a growing number of proteins which are reported to reside in multiple
compartments within the eukaryotic cell. However, lack of appropriate methods
limits our knowledge on the true extent of this phenomenon. In this study, we
demonstrate a novel application of beta-galactosidase alpha-complementation to
study dual distribution of proteins in yeast cells. Using a simple colony color
phenotype, we show that alpha-complementation depends on co-compartmentalization
of alpha and omega fragments and exploit this to probe dual localization of
proteins between the cytosol and mitochondria in yeast. The quality of our assay
was assessed by analysis of the known dual targeted enzyme fumarase and several
mutant derivatives, which are exclusively localized to one or the other of these
subcellular compartments. Addition of the alpha fragment did not abolish the
enzymatic activity of the tagged proteins nor did it affect their localization.
By examining 10 yeast gene products for distribution between the cytosol and the
mitochondria, we demonstrate the potential of alpha-complementation to screen the
mitochondrial proteome for dual distribution. Our data indicate the distribution
of two uncharacterized proteins--Bna3 and Nif3--between the cytosol and the
mitochondria.
PMID- 17034790
TI - Muscle-derived but not centrally derived transgene GDNF is neuroprotective in
G93A-SOD1 mouse model of ALS.
AB - Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor
for motoneurons (MNs), and is considered a potential agent for the treatment of
amyotrophic lateral sclerosis (ALS) and other MN diseases. The effectiveness of
GDNF may depend significantly upon its route of delivery to MNs. In this study we
tested the neuroprotective effects of target-derived and centrally derived GDNF
in the G93A-SOD1 mouse model of ALS using a transgenic approach. We found that
overexpression of GDNF in the skeletal muscle (Myo-GDNF mice) significantly
delayed the onset of disease and increased the life span of G93A-SOD1 mice by 17
days. The duration of disease also increased by 8.5 days, indicating that GDNF
slowed down the progression of disease. Locomotor performance in Myo-GDNF/G93A
SOD1 mice was also significantly improved. The behavioral improvement correlated
well with anatomical and histological data. We demonstrated that muscle-derived
GDNF resulted in increased survival of spinal MNs, and twice as many MNs survived
in end-stage double transgenic mice compared to end-stage G93A-SOD1 mice. Muscle
derived GDNF also had profound effects on muscle innervation and axonal
degeneration. Significantly higher numbers of completely or partially innervated
NMJs and large caliber myelinated axons were found in double transgenic mice. In
contrast, we demonstrated that overexpression of GDNF in astrocytes in the CNS
(GFAP-GDNF mice) failed to demonstrate any neuroprotective effects in G93A-SOD1
mice both on behavioral and histological levels. These data indicate that
retrograde transport and signaling of GDNF is more physiological and effective
for ALS treatment than anterogradely transported GDNF.
PMID- 17034791
TI - Control of neurogenesis and tyrosine hydroxylase expression in neural progenitor
cells through bHLH proteins and Nurr1.
AB - The production of dopamine (DA) neurons from neural progenitor cells (NPC) is of
particular interest as these neurons degenerate in Parkinson's disease. Here, we
report that the characteristics of NPC from the ventral midbrain (NPC(VM)) and
the striatum (NPC(STR)) are intrinsically determined. A detailed analysis of the
VM during development revealed Ngn2 and Mash1 expression in a DA progenitor
domain. Interestingly, over-expression of either Ngn2 or Mash1 induced
neurogenesis from expanded NPC(VM). Whereas Ngn2 inhibited cell division and the
production of neurons even in the presence of mitogens, Mash1 allowed the
progenitors to divide while retaining neurogenic potential. However, none of the
new neurons derived by over-expressing Ngn2 or Mash1 were positive for DA
neuronal markers such as tyrosine hydroxylase. Nurr1 over-expression increased TH
levels in a dose-dependant manner within both neurons and glia, suggesting a non
neuronal-specific activation of this enzyme by Nurr1. Double infection with Nurr1
and either Ngn2 or Mash1 resulted in the production of small numbers of TH+
neurons, which were larger in size when derived from NPC(VM) compared to
NPC(STR). These data provide proof of concept that over-expression of multiple
transcription factors can drive the fate of NPC first towards neurons, and then
towards the DA phenotype. However, further factors may be required to generate
fully functional DA neurons.
PMID- 17034792
TI - PCR detection of Anaplasma platys in blood and tissue of dogs during acute phase
of experimental infection.
AB - Four dogs were experimentally infected with Anaplasma platys to determine changes
in real-time TaqMan PCR detection in blood and tissue, microscopically detectable
parasitemia, and platelet concentrations during the first 28 days of infection.
Buffy-coat blood cells were PCR positive for A. platys DNA at 4 days after
inoculation and remained positive in all dogs until day 14. Marked
thrombocytopenia and low parasitemia occurred in dogs during that initial period.
During 17 and 28 days post-inoculation, the PCR results on buffy-coat blood cells
were intermittently negative in each dog with marked thrombocytopenia and no
microscopic evidence of parasitemia. Bone marrow and splenic aspirates collected
from the A. platys-infected dogs were tested by real-time TaqMan PCR. Two dogs
were PCR positive in spleen and marrow at 28 days post-inoculation, when PCR
results for buffy-coat blood cells were negative. Spleen and/or bone marrow
samples should be considered as additional samples for PCR testing of dogs,
particularly when blood samples are PCR negative during the acute phase of A.
platys infection.
PMID- 17034794
TI - Psychological stressors as a model of maternal adversity: diurnal modulation of
corticosterone responses and changes in maternal behavior.
AB - Maternal adversity is associated with long-lasting consequences on cognitive
development, behavior and physiological responses in rat offspring. Few studies
have examined whether repeated maternal stress produces repeated activation of
the hypothalamus-pituitary-adrenal (HPA) axis in mothers and whether it modifies
maternal behavior. Here, we tested a novel model of perinatal stress using
repeated exposure to "purely" psychological stressors throughout the gestation
and lactation periods in rats. We first tested the diurnal influences of repeated
1-h strobe light exposure on maternal corticosterone secretion. Despite the
hyporesponsiveness to stress documented in late pregnant and lactating mothers,
we observed an enhanced response to strobe light in the afternoon compared to the
morning in stressed mothers during lactation. Next, dams were exposed to 24-h
forced foraging followed by 10-h wet bedding during the diurnal peak of
corticosterone secretion. Although no corticosterone responses to forced foraging
and wet bedding were observed, the combination of both stressors had a
significant effect on maternal behavior. Mother-pup interactions were
significantly altered during the first 8 days of lactation. Taken together, these
findings suggest that lactating mothers maintain responsiveness to specific and
repeated psychological stressors, in particular at the time of the diurnal peak
in corticosterone secretion. Depending on the stressor applied, either
neuroendocrine activation or changes in maternal behavior might be important
determinants of the long-term consequences in the offspring. The combination of
forced foraging, wet bedding and strobe light might represent a novel model of
mild maternal adversity using "purely" psychological stressors.
PMID- 17034793
TI - A novel analytical method for in vivo phosphate tracking.
AB - Genetically-encoded fluorescence resonance energy transfer (FRET) sensors for
phosphate (P(i)) (FLIPPi) were engineered by fusing a predicted Synechococcus
phosphate-binding protein (PiBP) to eCFP and Venus. Purified fluorescent
indicator protein for inorganic phosphate (FLIPPi), in which the fluorophores are
attached to the same PiBP lobe, shows P(i)-dependent increases in FRET
efficiency. FLIPPi affinity mutants cover P(i) changes over eight orders of
magnitude. COS-7 cells co-expressing a low-affinity FLIPPi and a Na(+)/P(i) co
transporter exhibited FRET changes when perfused with 100 microM P(i),
demonstrating concentrative P(i) uptake by PiT2. FLIPPi sensors are suitable for
real-time monitoring of P(i) metabolism in living cells, providing a new tool for
fluxomics, analysis of pathophysiology or changes of P(i) during cell migration.
PMID- 17034795
TI - gamma-Glutamyltransferase predicts cardiovascular death among Japanese women.
AB - The clinical importance of gamma-glutamyltransferase (GGT) has recently been
debated. Although some studies have suggested that the relationship between GGT
and cardiovascular disease (CVD) mortality is independent of alcohol consumption,
to our knowledge no studies have reported the relationship between GGT and CVD
mortality in never-drinker subgroups. Since Japanese women are known to have a
lower prevalence of alcohol consumption, we examined whether GGT predicts CVD
mortality in never-drinkers. We followed 2724 Japanese men and 4122 Japanese
women without prior CVD or liver dysfunction for 9.6 years and observed 83 and 82
CVD deaths, respectively. Current alcohol drinkers comprised 59% of men and 7% of
women. Among women, the multiple adjusted hazard ratio (HR) for CVD mortality
compared with the reference group (GGT: 1-12 U/L) was 2.88 (95% confidence
interval (CI), 1.14-7.28) for the elevated group (GGT>or=50 U/L). This positive
relationship was unchanged in the never-drinkers subgroup (HR for log-transformed
continuous GGT, 1.62 (95% CI, 1.11-2.37)). No significant relationships were
observed in men. GGT displays a strong positive association with CVD mortality
among Japanese women, for whom the prevalence of ever-drinkers is very low.
Exploring the significance and biological mechanisms of GGT might provide useful
insights into CVD prevention.
PMID- 17034796
TI - Suprascapular nerve block results in a compensatory increase in deltoid muscle
activity.
AB - A balance exists between the deltoid and rotator cuff contribution to arm
elevation. Both cadaver and computer models have predicted an increase in deltoid
muscle force with dysfunction of the rotator cuff. The goal of the present study
was to verify this phenomenon in vivo by examining the effects of paralysis of
the supraspinatus and infraspinatus muscles with a suprascapular nerve block on
the electrical activity of seven shoulder muscles. Electromyographic data were
collected before and after the administration of the block. The block resulted in
a significant increase in muscle activity for all heads of the deltoid, with a
higher percentage increase noted at lower elevation angles. Although the deltoid
activity was reduced as the subjects recovered from the block, even low levels of
cuff dysfunction were found to result in increased deltoid activity. These
results suggest that even small disruptions in the normal function of some
rotator cuff muscles (e.g., due to fatigue or impingement syndrome), may result
in an increase in deltoid activity. It is possible that such compensation may
result in higher superior loads at the glenohumeral joint, possibly increasing
the risk of tendon damage.
PMID- 17034797
TI - Three-dimensional computer simulation of radiostereometric analysis (RSA) in
distal radius fractures.
AB - Physical phantom models have conventionally been used to determine the accuracy
and precision of radiostereometric analysis (RSA) in various orthopaedic
applications. Using a phantom model of a fracture of the distal radius it has
previously been shown that RSA is a highly accurate and precise method for
measuring both translation and rotation in three-dimensions (3-D). The main
shortcoming of a physical phantom model is its inability to mimic complex 3-D
motion. The goal of this study was to create a realistic computer model for
preoperative planning of RSA studies and to test the accuracy of RSA in measuring
complex movements in fractures of the distal radius using this new model. The 3-D
computer model was created from a set of tomographic scans. The simulation of the
radiographic imaging was performed using ray-tracing software (POV-Ray). RSA
measurements were performed according to standard protocol. Using a two-part
fracture model (AO/ASIF type A2), it was found that for simple movements in one
axis, translations in the range of 25microm-2mm could be measured with an
accuracy of +/-2microm. Rotations ranging from 16 degrees to 2 degrees could be
measured with an accuracy of +/-0.015 degrees . Using a three-part fracture model
the corresponding values of accuracy were found to be +/-4microm and +/-0.031
degrees for translation and rotation, respectively. For complex 3-D motion in a
three-part fracture model (AO/ASIF type C1) the accuracy was +/-6microm for
translation and +/-0.120 degrees for rotation. The use of 3-D computer modelling
can provide a method for preoperative planning of RSA studies in complex
fractures of the distal radius and in other clinical situations in which the RSA
method is applicable.
PMID- 17034798
TI - Prediction of strength and strain of the proximal femur by a CT-based finite
element method.
AB - Hip fractures are the most serious complication of osteoporosis and have been
recognized as a major public health problem. In elderly persons, hip fractures
occur as a result of increased fragility of the proximal femur due to
osteoporosis. It is essential to precisely quantify the strength of the proximal
femur in order to estimate the fracture risk and plan preventive interventions.
CT-based finite element analysis could possibly achieve precise assessment of the
strength of the proximal femur. The purpose of this study was to create a
simulation model that could accurately predict the strength and surface strains
of the proximal femur using a CT-based finite element method and to verify the
accuracy of our model by load testing using fresh frozen cadaver specimens.
Eleven right femora were collected. The axial CT scans of the proximal femora
were obtained with a calibration phantom, from which the 3D finite element models
were constructed. Materially nonlinear finite element analyses were performed.
The yield and fracture loads were calculated, while the sites where elements
failed and the distributions of the principal strains were determined. The strain
gauges were attached to the proximal femoral surfaces. A quasi-static compression
test of each femur was conducted. The yield loads, fracture loads and principal
strains of the prediction significantly correlated with those measured (r=0.941,
0.979, 0.963). Finite element analysis showed that the solid elements and shell
elements in undergoing compressive failure were at the same subcapital region as
the experimental fracture site.
PMID- 17034799
TI - Mechanics of arterial subfailure with increasing loading rate.
AB - Arterial subfailure leads to delayed symptomatology and high morbidity and
mortality rates, particularly for the thoracic aorta and carotid arteries.
Although arterial injuries occur during high-velocity automotive collisions,
previous studies of arterial subfailure focused on quasi-static loading. This
investigation subjected aortic segments to increasing loading rates to quantify
effects on elastic, subfailure, and ultimate vessel mechanics. Sixty-two
specimens were axially distracted, and 92% demonstrated subfailure before
ultimate failure. With increasing loading rate, stress at initial subfailure and
ultimate failure significantly increased, and strain at initial subfailure and
ultimate failure significantly decreased. Present results indicate increased
susceptibility for arterial subfailure and/or dissection under higher-rate
extension. According to the present results, automotive occupants are at greater
risk of arterial injury under higher velocity impacts due to greater body segment
motions in addition to decreased strain tolerance to subfailure and catastrophic
failure.
PMID- 17034800
TI - Preparation of dye-ligand affinity chromatographic packings based on monodisperse
poly(glycidylmethacrylate-co-ethylenedimethacrylate) beads and their
chromatographic properties.
AB - Monodisperse porous particles, poly(glycidylmethacrylate-co
ethylenedimethacrylate), P(GMA-EDMA) beads with diameter of 7 microm were
prepared by a single-step swelling and polymerization method. The polymer
particles were advantaged through immobilization of Procion Bule MX-R, which was
incubated by epichlorohydrin via the epoxide groups on the particles surface. The
Procion Bule MX-R-immobilized P(GMA-EDMA) beads were mechanically stable and
acted as the rigid matrix for column chromatography in HPLC mode. The
chromatographic properties of the dye-ligand affinity chromatographic stationary
phase for biopolymers separation are discussed. This affinity column has
advantages of enabling biopolymer separation, high efficiency and low
backpressure. Lysozyme and BSA were fast separated within 10min using this
affinity column. The column was also used for the purification of lysozyme from
chicken egg white.
PMID- 17034801
TI - On-line derivatization gas chromatography with furan chemical ionization tandem
mass spectrometry for screening of amphetamines in urine.
AB - A simple alternative method with minimal sample pretreatment is investigated for
screening of amphetamines in small volume (using only 20 microL) of urine sample.
The method is sensitive and selective. The method uses gas chromatography (GC)
direct sample introduction (DSI) for on-line derivatization (acylation) of
amphetamines to improve sensitivity. Furan as chemical ionization (CI) reagent in
conjunction with tandem mass spectrometry (MS/MS) is used to improve selectivity.
Low background with sharp protonated molecular ion peaks of analytes is the
evidence of improvement in sensitivity and selectivity. Blank urine samples
spiked with known amounts of amphetamine, methamphetamine, 3,4
methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine and 3,4
methylenedioxyethylamphetamine is analyzed. Selected ion monitoring of the
characteristic product ions (m/z 119+136+150+163) using furan CI-MS/MS in
positive ion mode is used for quantification. Limits of detection (LOD) between
0.4 and 1.0 ng mL(-1) and limits of quantitation (LOQ) between 1.0 and 2.0 ng mL(
1) are established. Linear response over the range of 1-1000 ng mL(-1)
(r(2)>0.997) is observed for all analytes, except for methamphetamine (2.0-1000
ng mL(-1)). Good accuracy between 86 and 113% and precision ranging from 4 to 18%
is obtained. The method is also tested on real samples of urine from suspected
drug abusers. This method could be used for screening and determination of
amphetamines in urine samples, however needs additional work for full validation.
PMID- 17034802
TI - New findings for in-gel digestion accelerated by high-intensity focused
ultrasound for protein identification by matrix-assisted laser desorption
ionization time-of-flight mass spectrometry.
AB - New findings in sample treatment based on high-intensity focused ultrasound
(HIFU) for protein digestion after polyacrylamide gel electrophoresis separation
are presented. The following variables were studied: (i) sample volume; (ii)
sonotrode diameter; (iii) previous protein denaturation; (iv) cooling; (v) enzyme
concentration; and (vi) protein concentration. Results showed that positive
protein identification could be done after protein separation by gel
electrophoresis through peptide mass fingerprint (PMF) in a volume as low as 25
microL. The time needed was less than 2 min and no cooling was necessary. The
importance of the sonotrode diameter was negligible. On the other hand, protein
denaturation before sonication was a trade-off for the success of procedure here
described. The protein coverage was raised from 5 to 30%, and the number of
peptides matching the proteins was also increased in a percentage ranging 10-100%
when the classical overnight treatment is compared with the proposed HIFU
procedure. The minimum amount of protein that can be identified using the HIFU
sample treatment by matrix-assisted laser desorption ionization time-of-flight
mass spectrometry (MALDI-TOF-MS) was 0.06 microg. The lower concentration of
trypsin successfully used to obtain an adequate protein digestion was 3.6
microg/mL.
PMID- 17034803
TI - Modeling and simulation of protein uptake in cation exchanger visualized by
confocal laser scanning microscopy.
AB - Confocal laser scanning microscopy (CLSM) has been extensively applied in the
area of protein chromatography to investigate the uptake mechanism of protein in
adsorbents. However, due to the light attenuation in the deeper layers of a
specimen, quantitative analysis using CLSM data is still far from reality. In
this work, an attenuation equation for describing the darkening of the CLSM image
in the deeper scanning layers was developed. Bovine serum albumin (BSA)
adsorption to SP Sepharose FF was performed by batch adsorption and micro-column
chromatography on which protein concentration in single absorbents were
visualized by CLSM. The parameters in the equation were estimated by fitting it
to the fluorescence intensity profiles obtained at adsorption equilibrium, and
then the equation was used to simulate the effect caused by the light scattering
and absorption. CLSM analysis demonstrated that BSA adsorption to SP Sepharose FF
followed the shrinking core pattern and was predicted reasonably well by the pore
diffusion model in combination with the attenuation equation. By comparison of
the CLSM data with the simulations, it shows that the attenuation equation was
useful to demonstrate the validity of an intraparticle mass transport model for
the estimation of intraparticle protein concentration profiles.
PMID- 17034804
TI - Aromatic resin characterisation by gas chromatography-mass spectrometry. Raw and
archaeological materials.
AB - An analytical procedure based on alkaline hydrolysis, solvent extraction and
trimethyl-silylation followed by gas chromatography-mass spectrometry (GC-MS)
analysis was used to study the chemical composition of benzoe and storax resins,
water-insoluble exudates of trees of the Styrax and Liquidambar genus. They are
chemically characterised by having aromatic acids, alcohols and esters as their
main components and are thus known as aromatic and/or balsamic resins. This
analytical procedure allowed us to characterise the main components of the two
resins and, even though cinnamic acid is the main component of both the resins,
the presence of other characteristic aromatic compounds and triterpenes permitted
us to distinguish between the two materials. All the compounds identified in
benzoe resin were detected in an archaeological organic residue from an Egyptian
ceramic censer (fifth to seventh centuries a.d.), thus proving that this resin
was used as one of the components of the mixture of organic materials burned as
incense. These results provide the first chemical evidence of the presence of
benzoe resin in an archaeological material from Mediterranean area.
PMID- 17034805
TI - High sensitivity separation and detection of heparan sulfate disaccharides.
AB - Eight Delta-disaccharide standards from heparan sulfate/heparin were derivatized
with the fluorophore 4,4-difluoro-5,7- dimethyl-4-bora-3a,4a-diaza-s-indacene-3
propionic acid, hydrazide (BODIPY) via formation of a Schiff's base and separated
using HPAEC on a Propac PA1 column with a linear salt gradient and isocratic 150
mM NaOH. Detection was with an in-line fluorescence detector. The standard
deviation (sigma(n-1)) in retention times were 0.7-2% over nine runs. The limit
of detection, was 100 fmol (100 x 10(-15)mol) of BODIPY labeled Delta
disaccharides, representing considerably improved detection compared to other
fluorophore labeled derivatives and, unlike these, required no further
purification steps. Separation and improved detection of BODIPY-Delta
disaccharide conjugates will assist the structural analysis of HS and the
development of improved sequencing methodologies.
PMID- 17034806
TI - Equilibrium and dynamic aspects of dodecyltrimethylammonium bromide adsorption at
the air/water interface in the presence of lambda-carrageenan.
AB - In this work we present equilibrium and dynamic surface tension together with
dilational elasticity data for dodecyltrimethylammonium bromide in the presence
of lambda-carrageenan, a sulfated polysaccharide extracted from algae. The
critical aggregation concentration and (CAC) and critical micellar concentration
CMC of the mixed system were determined and shown to have a direct influence on
the elasticity modulus. The behavior of the adsorption kinetics was shown to be
dependent on the surfactant to polyelectrolyte charge ratio or excess species in
the bulk solution.
PMID- 17034807
TI - Aggregation and gelation kinetics of fumed silica-ethanol suspensions.
AB - The kinetics of aggregation and gelation of fumed silica suspended in ethanol
were investigated as a function of volume fraction. At low particle
concentrations, gelation is well described by aggregation into a primary minimum
arising from hydrogen bonding and dispersion forces. The gelation is extremely
slow due to an energetic barrier (approximately 25 kT) in the interparticle
potential associated with solvation forces. The solvation forces also contribute
to the formation of a secondary minimum in the interparticle potential. The depth
of this minimum (approximately 3 kT) is sufficient that, at a critical particle
concentration, long-range diffusion is arrested due to the short-range
attractions and the cooperative nature of particle interactions, as described by
mode coupling theory. The presence of the secondary minimum is also observed in
the microstructure of the gels studied using X-ray scattering. These observations
reinforce the importance of understanding the role of solvent-particle
interactions in manipulating suspension properties.
PMID- 17034808
TI - Lysozyme binding onto cat-anionic vesicles.
AB - Mixing aqueous sodium dodecylsulfate with cetyltrimethylammonium bromide
solutions in mole ratios close to (1.7/1.0) allows the formation of cat-anionic
vesicles with an excess of negative charges on the outer surface. The vesicular
dispersions are mixed with lysozyme, and interact electrostatically with the
positive charges on the protein, forming lipo-plexes. Dielectric relaxation, zeta
potential, and light scattering indicate the occurrence of interactions between
vesicles and the protein. According to CD, the vesicle-adsorbed protein retains
its native conformation. Binding and surface saturation, inferred by dielectric
relaxation and zeta-potential, fulfil a charge neutralisation stoichiometry.
Adsorbed lysozyme promotes the vesicle clustering and is concomitant with the
lipo-plexes flocculation. Above the charge neutralisation threshold, lysozyme in
excess remains dispersed in molecular form. Attempts were made to determine in
what conditions protein release from the vesicles occurs. Accordingly, the full
neutralisation of sodium dodecylsulfate in excess by cetyltrimethylammonium
bromide ensures the lipo-plexes break-up, the precipitation of the mixed
surfactants and the protein release in native form.
PMID- 17034809
TI - The adsorption behavior of crystal violet in functionalized sporopollenin
mediated column arrangements.
AB - The adsorption behavior of Crystal Violet (CV) on a sporopollenin-based solid
phase, carboxylated diaminoethane sporopollenin (CDAE-S), was investigated under
column conditions, and the obtained breakthrough profiles were used in
evaluations and quantifications. The adsorption capacity of the CDAE-S was
observed to be considerably higher than that of diaminoethane sporopollenin (DAE
S), revealing the importance of electrostatic interactions and carboxyl groups in
the adsorption of CV on the CDAE-S. The binding of CV on the DAE-S was found to
be a typical nonspecific adsorption, whilst cation-exchange was proposed as the
main mechanism for monolayer adsorption of CV on the CDAE-S. Hence in the present
study, the cation-exchange is suggested as an effective process for removal and
recovery of CV from aqueous effluents, and in view of the pH point of zero charge
matter, multifunctionality of the CDAE-S is discussed in detail, and various
application possibilities based on "aminocarboxylic acid" functionality are also
drawn.
PMID- 17034810
TI - Otarine Herpesvirus-1, not papillomavirus, is associated with endemic tumours in
California sea lions (Zalophus californianus).
AB - The purpose of this study was to determine if Otarine Herpesvirus-1 (OtHV-1) is
associated with the presence of urogenital carcinomas in California sea lions.
Polymerase chain reaction (PCR) analysis with primers specific for OtHV-1 was
used to compare the prevalence of OtHV-1 infection in 15 sea lions affected by
urogenital carcinoma with that of age-matched and juvenile tumour-free animals,
and animals with tumours of non-urogenital origin. The herpesvirus was more
prevalent (100%) and more widespread in the 15 animals with urogenital carcinoma
than in 25 control animals, and was most often found in the urogenital tissue
(vagina and prostate) and in the draining lymph nodes. Moreover, OtHV-1 DNA was
not found in any juvenile animal, or in the neoplastic tissues of animals with
non-urogenital tumours. Papillomavirus-specific PCR analysis of urogenital
carcinoma tissues detected papillomavirus sequences in only one carcinomatous
tissue. Further studies are needed to determine if OtHV-1 contributes to
oncogenesis in the California sea lion; these data show, however, that OtHV-1 is
associated with urogenital carcinomas, is preferentially present in urogenital
tissues, and may be sexually transmitted. Papillomaviruses, which are known to
contribute to urogenital tumours in other species, did not appear to be
associated with the sea lion carcinomas.
PMID- 17034811
TI - The thyroid gland in bottlenose dolphins (Tursiops truncatus) from the Texas
coast of the Gulf of Mexico: normal structure and pathological changes.
AB - Fresh thyroid glands (n=60) from Atlantic bottlenose dolphins that died after
stranding along the Texas coast between 1991 and 2005 were examined. Organ weight
ranged from 11 g in a neonate (length 109 cm) to 58 g in a large (249 cm) male.
More typical weights were 25-45 g (mean=30.6 g). Glands tended to be larger in
pregnant and lactating females (mean 37.4 g; n=5) than in non-pregnant animals of
comparable size. In infancy, the gland tended to be compact, relatively
homogeneous, and sometimes partly lobular, but with advancing age it became more
lobular, the lobules being defined by fibrous bands. In one 8-year-old female
(233 cm), and in a large male (295 cm) aged>25 years the gland was represented by
a cluster of lobules. Lobulation was not necessarily accompanied by increased
weight, distinguishing it from hyperplasia. With age, variation in follicle size
and colloid density tended to increase. Two animals (3%) had adenomas and five
(8%) had discrete hyperplastic nodules, not to be confused with lobulation. Five
(8%) had macroscopically identifiable colloid-filled cysts (1-4 mm in diameter).
Nine animals (15%) had squamous cysts (4-15 mm) containing creamy white fluid.
Other abnormalities included patchy or diffuse interstitial fibrosis (six cases,
10%) amyloidosis (two cases), thyroiditis (one case) and vasculitis (one case).
No malignant neoplasms were found. Cells presumed to be C cells (light cells,
parafollicular cells) were identified immunohistochemically with synaptophysin
antibody.
PMID- 17034812
TI - Word acquisition, retention, and transfer: findings from contextual and isolated
word training.
AB - Successful reading instruction entails not only acquiring new words but also
remembering them after training has finished and accessing their word-specific
representations when they are encountered in new text. We report two studies
demonstrating that acquisition, retention, and transfer of unfamiliar words were
affected differentially by isolated word and context training. Materials were
individualized to include only those words that average readers in second grade
were unable to name in context. Different words were trained in each condition;
context training presented words in stories, and isolated word training presented
words on flashcards. Together, the studies show that context training promotes
word acquisition beyond that experienced from reading words in isolation.
Contrary to the prevailing opinion, memory performance for words trained in
context and in isolation did not differ; children demonstrated excellent
retention over an 8-day interval in both conditions. Finally, transfer was
maximized when the congruency between training and testing was high. Therefore,
when reading trained words in novel circumstances, the best method of training
was mediated by the transfer task employed at test.
PMID- 17034813
TI - Simultaneous detection of a cell surface antigen and apoptosis by microwave
sensitized TUNEL assay on paraffin sections.
AB - The TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)
technique has been described as a sensitive method for detection of apoptotic
nuclei in tissues and preferential staining of apoptotic strand breaks. Short
term microwave pre-treatment, a non-enzymatic pre-treatment technique of antigen
retrieval, has been demonstrated to optimize the TUNEL method for in situ
detection of apoptotic cells in formalin-fixed paraffin-embedded tissue sections.
In the present study, we sensitized internal mammary artery sections by short
term microwave pre-treatment and used a two-step indirect enzymatic method to
gain as an end product differentially stained cells, namely TUNEL-positive cells
and these positive for the surface marker von Willebrand factor (vWF). This
technique enables to clearly distinguish between apoptotic, non-apoptotic and vWF
positive cells that are phenotypic for endothelial cells. Phenotypic
identification of cells is simplified by double staining with cell surface
markers. This rapid, sensitive and reproducible technique allows simultaneous
detection of DNA fragmentation and phenotypic markers in the same paraffin
embedded human tissue section.
PMID- 17034814
TI - Primary culture of hemocytes from the Caribbean spiny lobster, Panulirus argus,
and their susceptibility to Panulirus argus Virus 1 (PaV1).
AB - Primary cultures of hemocytes from the Caribbean spiny lobster Panulirus argus
were developed for studies on the in vitro propagation of Panulirus argus Virus 1
(PaV1). A modified Leibovitz L-15 medium supported the best survival of hemocytes
in in vitro primary cultures. However, degradation of the cultures occurred
rapidly in the presence of granulocytes. A Percoll step gradient was used to
separate hemocytes into three subpopulations enriched in hyalinocytes,
semigranulocytes, and granulocytes, respectively. When cultured separately,
hyalinocytes and semigranulocytes maintained higher viability ( approximately
80%) after 18 days incubation compared with granulocytes, which degraded over 2-3
days. Susceptibility of the cell types was investigated in challenge studies with
PaV1. Hyalinocytes and semigranulocytes were susceptible to PaV1. Cytopathic
effects (CPE) were observed as early as 12h post-inoculation, and as the
infection progressed, CPE became more apparent, with cell debris and cellular
exudates present in inoculated cultures. Cell lysis was noticeable within 24h of
infection. The presence of virus within cells was further confirmed by in situ
hybridization using a specific DNA probe. The probe gave a unique staining
pattern to cells infected with PaV1 24-h post-inoculation. Cells in the control
treatment were intact and negative to hybridization. This assay was further
applied to the quantification of infectious virus in hemolymph using a 50% tissue
culture infectious dose assay (TCID(50)) based on CPE. These tools will now allow
the quantification of PaV1 using established culture-based methods.
PMID- 17034815
TI - Cognate ligand domain mapping for enzymes.
AB - Here, we present an automatic assignment of potential cognate ligands to domains
of enzymes in the CATH and SCOP protein domain classifications on the basis of
structural data available in the wwPDB. This procedure involves two steps;
firstly, we assign the binding of particular ligands to particular domains;
secondly, we compare the chemical similarity of the PDB ligands to ligands in
KEGG in order to assign cognate ligands. We find that use of the Enzyme
Commission (EC) numbers is necessary to enable efficient and accurate cognate
ligand assignment. The PROCOGNATE database currently has cognate ligand mapping
for 3277 (4118) protein structures and 351 (302) superfamilies, as described by
the CATH and (SCOP) databases, respectively. We find that just under half of all
ligands are only and always bound by a single domain, with 16% bound by more than
one domain and the remainder of the ligands showing a variety of binding modes.
This finding has implications for domain recombination and the evolution of new
protein functions. Domain architecture or context is also found to affect
substrate specificity of particular domains, and we discuss example cases. The
most popular PDB ligands are all found to be generic components of
crystallisation buffers, highlighting the non-cognate ligand problem inherent in
the PDB. In contrast, the most popular cognate ligands are all found to be
universal cellular currencies of reducing power and energy such as NADH, FADH2
and ATP, respectively, reflecting the fact that the vast majority of enzymatic
reactions utilise one of these popular co-factors. These ligands all share a
common adenine ribonucleotide moiety, suggesting that many different domain
superfamilies have converged to bind this chemical framework.
PMID- 17034816
TI - A novel lysine-rich domain and GTP binding motifs regulate the nucleolar
retention of human guanine nucleotide binding protein, GNL3L.
AB - A variety of G-proteins and GTPases are known to be involved in nucleolar
function. We describe here a new evolutionarily conserved putative human GTPase,
guanine nucleotide binding protein-like 3-like (GNL3L). Genes encoding proteins
related to GNL3L are present in bacteria and yeast to metazoa and suggests its
critical role in development. Conserved domain search analysis revealed that the
GNL3L contains a circularly permuted G-motif described by a G5-G4-G1-G2-G3
pattern similar to the HSR1/MMR1 GTP-binding protein subfamily. Highly conserved
and critical residues were identified from a three-dimensional structural model
obtained for GNL3L using the crystal structure of an Ylqf GTPase from Bacillus
subtilis. We demonstrate here that GNL3L is transported into the nucleolus by a
novel lysine-rich nucleolar localization signal (NoLS) residing within 1-50 amino
acid residues. NoLS identified here is necessary and sufficient to target the
heterologous proteins to the nucleolus. We show for the first time that the
lysine-rich targeting signal interacts with the nuclear transport receptor,
importin-beta and transports GNL3L into the nucleolus. Interestingly, depletion
of intracellular GTP blocks GNL3L accumulation into the nucleolar compartment.
Furthermore, mutations within the G-domains alter the GTP binding ability of
GNL3L and abrogate wild-type nucleolar retention even in the presence of
functional NoLS, suggesting that the efficient nucleolar retention of GNL3L
involves activities of both basic NoLS and GTP-binding domains. Collectively,
these data suggest that GNL3L is composed of distinct modules, each of which
plays a specific role in molecular interactions for its nucleolar retention and
subsequent function(s) within the nucleolus.
PMID- 17034817
TI - Crystal structures of mouse 17alpha-hydroxysteroid dehydrogenase (apoenzyme and
enzyme-NADP(H) binary complex): identification of molecular determinants
responsible for the unique 17alpha-reductive activity of this enzyme.
AB - Very recently, the mouse 17alpha-hydroxysteroid dehydrogenase (m17alpha-HSD), a
member of the aldo-keto reductase (AKR) superfamily, has been characterized and
identified as the unique enzyme able to catalyze efficiently and in a
stereospecific manner the conversion of androstenedione (Delta4) into
epitestosterone (epi-T), the 17alpha-epimer of testosterone. Indeed, the other
AKR enzymes that significantly reduce keto groups situated at position C17 of the
steroid nucleus, the human type 3 3alpha-HSD (h3alpha-HSD3), the human and mouse
type 5 17beta-HSD, and the rabbit 20alpha-HSD, produce only 17beta-hydroxy
derivatives, although they possess more than 70% amino acid identity with
m17alpha-HSD. Structural comparisons of these highly homologous enzymes thus
offer an excellent opportunity of identifying the molecular determinants
responsible for their 17alpha/17beta-stereospecificity. Here, we report the
crystal structure of the m17alpha-HSD enzyme in its apo-form (1.9 A resolution)
as well as those of two different forms of this enzyme in binary complex with
NADP(H) (2.9 A and 1.35 A resolution). Interestingly, one of these binary complex
structures could represent a conformational intermediate between the apoenzyme
and the active binary complex. These structures provide a complete picture of the
NADP(H)-enzyme interactions involving the flexible loop B, which can adopt two
different conformations upon cofactor binding. Structural comparison with binary
complexes of other AKR1C enzymes has also revealed particularities of the
interaction between m17alpha-HSD and NADP(H), which explain why it has been
possible to crystallize this enzyme in its apo form. Close inspection of the
m17alpha-HSD steroid-binding cavity formed upon cofactor binding leads us to
hypothesize that the residue at position 24 is of paramount importance for the
stereospecificity of the reduction reaction. Mutagenic studies have showed that
the m17alpha-HSD(A24Y) mutant exhibited a completely reversed stereospecificity,
producing testosterone only from Delta4, whereas the h3alpha-HSD3(Y24A) mutant
acquires the capacity to metabolize Delta4 into epi-T.
PMID- 17034818
TI - Dementia with Lewy bodies.
AB - Advanced Parkinson's disease (PD) is frequently associated with dementia. The
pathogenesis of this dementia is complex, related to deficiency of several
biogenic amines and cortical Lewy body deposition, as well as co-existent age
related brain changes, both of the Alzheimer type and vascular. However,
degeneration of the cholinergic neurons in the nucleus basalis of Meynert may
have an important contribution to the cognitive decline. The dementia of PD has a
grave effect on the quality of life of the patients and their caregivers, as well
as a negative effect on their survival. The treatment of dementia associated with
PD with cholinesterase inhibitors produced gratifying (although limited) results.
Future studies should define the exact role of these agents in the treatment of
the dementia of PD. Another major problem presented by demented PD patients is
the occurrence of delusions and hallucinations, which make the life of patients
and caregivers miserable. Classical neuroleptics are of course contra-indicated
in these patients but recent data increase concern about the safety of novel
derivatives, leaving a void in the pharmacological armamentarium available when
these manifestations appear.
PMID- 17034819
TI - Plantainoside D protects adriamycin-induced apoptosis in H9c2 cardiac muscle
cells via the inhibition of ROS generation and NF-kappaB activation.
AB - Plantainoside D (PD), was isolated from the leaves of Picrorhiza
scrophulariiflora (Scrophulariaceae). The anti-oxidative activity of PD was
evaluated based on scavenging effects on hydroxyl radicals and superoxide anion
radicals. Adriamycin (ADR) is a potent anti-tumor drug known to cause severe
cardiotoxicity. Although ADR generates free radicals, the role of free radicals
in the development of cardiac toxicity has not been understood. This study was
undertaken to investigate the protective effect of PD against ADR-induced
apoptosis. In vitro, ADR caused dose-dependent toxicity in H9c2 cardiac muscle
cells. Pre-treatment of the cardiac muscle cells with PD significantly reduced
ADR-induced apoptosis of cardiac muscle cells. PD inhibited the ROS produced by
ADR in the cardiac muscle cells. As well, PD increased GSH(glutathione), compared
with ADR. In response to ADR, NF-kappaB was activated in H9c2 cells. However the
treatment of PD reduced the activation of NF-kappaB. We also observed that the NF
kappaB inhibitor, PDTC, inhibited the cytotoxic effect on ADR-induced apoptosis
in cardiac muscle cells. In parallel, IkappaBalpha-dominant negative plasmid
overexpression abrogated ADR-induced apoptosis in H9c2 cardiac muscle cells. In
conclusion, these results suggest that Plantaionoside D can inhibit ADR-induced
apoptosis in H9C2 cardiac muscle cells via inhibition of ROS generation and NF
kappaB activation. The pure compound PD can be a potential candidate agent which
protects cardiotoxicity in ADR-exposed patients.
PMID- 17034820
TI - Anthropogenic effects on the smalltooth sawfish (Pristis pectinata) in the United
States.
AB - Bycatch mortality in net fisheries was the major reason for the decline of the
endangered smalltooth sawfish, Pristis pectinata, in the United States. These
fisheries have been reduced or eliminated in some states including Florida--where
most smalltooth sawfish are currently found in the United States. To determine
whether other factors are still affecting this species, we obtained non-net
fishery entanglement, injury, and mortality data by soliciting information from
anyone who may have encountered this species. Smalltooth sawfish were damaged by
marine pollution (e.g., polyvinyl chloride pipe, monofilament line, non
monofilament line) and injured by humans. Examples of injuries caused directly by
humans include removal of rostra, shooting an individual with a powerhead, and
shooting another with arrows. Many people are aware that the smalltooth sawfish
is protected by state and federal laws, but some are still not aware of (or
willing to accept) this status. The impacts of marine pollution and injuries
directly caused by humans on this endangered species can be ameliorated by
incorporating fisher education into the conservation and management processes.
PMID- 17034821
TI - Evidence for a dissociation of structural and semantic knowledge in dementia of
the Alzheimer type (DAT).
AB - Object recognition and naming deficits in dementia of the Alzheimer type (DAT)
have typically been attributed to deficits in semantic processing, with only a
few studies proposing loci of deficits other than semantic. One possible cause of
DAT object recognition impairments could involve deficits in processing
structural aspects of visually presented items. In this paper, we assess the
performance of a group of mild DAT patients on two tasks of structural access,
object decision, and the complete/incomplete task (based on part-whole matching
task), as well as on a semantic probes task, designed to assess the patients'
semantic knowledge of the same items for which structural knowledge had earlier
been assessed. The DAT patients were substantially impaired in their performance
on tasks of structural access. Further, no evidence for item-to-item consistency
in the DAT patients' errors for the structural and semantic tasks was found,
raising the possibility that structural and semantic knowledge may become
differentially impaired in DAT.
PMID- 17034824
TI - Better than a cure.
AB - A brief glance through the national papers and medical press shows the depth of
concern with the cost of delivering high quality, free at the point of access
healthcare to the population. However, at a time of increasingly greater demands
being placed on public health systems across the globe, the question of how we
can make health and healthcare both accessible to everyone and sustainable in the
long term is being posed. In this paper we provide an insight into how England is
responding to these challenges.
PMID- 17034823
TI - Assessment of microbiological water quality and its relation to human health in
Gaza Governorate, Gaza Strip.
AB - OBJECTIVE: To assess the contamination level of total and faecal coliforms in
water wells and distribution networks, and their association with human health in
Gaza Governorate, Gaza Strip. METHODS: Data were obtained from the Palestinian
Ministry of Health on contamination of total and faecal coliforms in water wells
and distribution networks, and on the incidence of water-related diseases in Gaza
Governorate. An interview questionnaire was conducted with 150 residents of Gaza.
RESULTS: The contamination level of total and faecal coliforms exceeded that of
the World Health Organization (WHO) limit for water wells and networks. However,
the contamination percentages in networks were higher than that in wells.
Giardiasis was strongly correlated with faecal coliform contamination in water
networks (r=0.7) compared with diarrhoeal diseases and hepatitis A (r=0.3 and
0.1, respectively). Diarrhoeal diseases were the highest self-reported diseases
among interviewees in Gaza city. Such diseases were more prevalent among people
using municipal water than people using desalinated water and water filtered at
home for drinking (OR=1.6). Intermittent water supply and sewage flooding seemed
to contribute largely to self-reported diseases. People in Gaza Strip have good
knowledge on drinking water contamination, and this is reflected in good
practice. CONCLUSIONS: Water quality has deteriorated in Gaza Strip. This may
contribute to the prevalence of water-related diseases. Self-reported diseases
among interviewees in Gaza City were associated with source of drinking water,
intermittent water supply, sewage flooding and age of water, and wastewater
networks.
PMID- 17034825
TI - Purinergic control of the quail rectum: modulation of adenosine 5'-triphosphate
mediated contraction with acetylcholine.
AB - Electrical field stimulation (EFS) induces frequency-dependent contractions of
the longitudinal muscle of isolated quail rectum which were sensitive to
tetrodotoxin. The aim of the present study was to investigate whether purinergic
neurons are implicated in the response to nerve stimulation. The shape of the EFS
induced contractile response was different depending on stimulus frequency; low
frequencies (0.5-2 Hz) induced fast monophasic contractions with a small
subsequent relaxation; whereas higher frequencies (5-50 Hz) induced biphasic
contractile response that comprised fast initial component (as in case of low
frequency) and a slow delayed contractile component in addition to the relaxation
that follows the fast contractile component. Prior application of atropine (10
microM) completely abolished the slow delayed component but significantly
enhanced the fast initial contractile component. Physostigmine (1-10 microM)
significantly enhanced the slow delayed component with an inhibitory effect on
the initial fast component. The nonspecific purinergic receptor antagonist,
suramin (100-500 microM) significantly inhibited the fast initial contractile
component with no significant effect on the slow delayed one. Complete blockade
of the fast component was achieved by prior application of a combination
consisted of suramin (50 microM) and pyridoxicalphosphate-6-azophenyl 2',4'
disulphonic acid tetrasodium (PPADS; 10 microM). Exogenous applications of
adenosine 5'-triphosphate and acetylcholine (10 microM each), produced
contractile responses that mimicked those induced by EFS. These data suggest that
ATP is the main noncholinergic excitatory transmitter controlling the contractile
activity of the quail rectum; and that its action could be modulated by
acetylcholine.
PMID- 17034826
TI - An epidermotropic canine papillomavirus with malignant potential contains an E5
gene and establishes a unique genus.
AB - A novel canine papillomavirus, CfPV-2, was cloned from a footpad lesion of a
golden retriever. Unlike the known canine oral papillomavirus (COPV), which has a
double-stranded DNA genome size of 8607 bps, the genome of CfPV-2 is 8101 bps.
Some of this size difference is due to an abbreviated early-late region (ELR),
which is 1200 bps shorter than that of COPV. However, CfPV-2 has other
differences from COPV, including the presence of an E5 ORF between the E2 gene
and the ELR and an enlarged E4 ORF (one of the largest PV E4 open reading
frames). The genome of CfPV-2 shares low homology with all the other
papillomaviruses and, even in the most highly conserved ORF of L1, the nucleotide
sequence shares only 57% homology with COPV. Due to this highly divergent DNA
sequence, CfPV-2 establishes a new PV genus, with its closest phylogenetic
relatives being amongst the Xi and Gamma genuses. CfPV-2 also has unique
biological features; it induces papillomas on footpads and interdigital regions
which, if infection is persistent, can progress to highly metastatic squamous
cell carcinoma. CfPV-2 does not induce oral papillomas in immunocompetent animals
and antibodies generated against COPV and CfPV-2 are type-specific. The
availability of a new canine papillomavirus with differing genetic and biological
properties now makes it possible to study type-specific host immune responses,
tissue tropism and the comparative analysis of viral gene functions in the dog.
PMID- 17034827
TI - Default assembly of early adenovirus chromatin.
AB - In adenovirus particles, the viral nucleoprotein is organized into a highly
compacted core structure. Upon delivery to the nucleus, the viral nucleoprotein
is very likely to be remodeled to a form accessible to the transcription and
replication machinery. Viral protein VII binds to intra-nuclear viral DNA, as do
at least two cellular proteins, SET/TAF-Ibeta and pp32, components of a chromatin
assembly complex that is implicated in template remodeling. We showed previously
that viral DNA-protein complexes released from infecting particles were sensitive
to shearing after cross-linking with formaldehyde, presumably after transport of
the genome into the nucleus. We report here the application of equilibrium
density gradient centrifugation to the analysis of the fate of these complexes.
Most of the incoming protein VII was recovered in a form that was not cross
linked to viral DNA. This release of protein VII, as well as the binding of
SET/TAF-Ibeta and cellular transcription factors to the viral chromatin, did not
require de novo viral gene expression. The distinct density profiles of viral DNA
complexes containing protein VII, compared to those containing SET/TAF-Ibeta or
transcription factors, were consistent with the notion that the assembly of early
viral chromatin requires both the association of SET/TAF-1beta and the release of
protein VII.
PMID- 17034828
TI - Microplitis demolitor bracovirus genome segments vary in abundance and are
individually packaged in virions.
AB - Polydnaviruses (PDVs) are distinguished by their unique association with
parasitoid wasps and their segmented, double-stranded (ds) DNA genomes that are
non-equimolar in abundance. Relatively little is actually known, however, about
genome packaging or segment abundance of these viruses. Here, we conducted
electron microscopy (EM) and real-time polymerase chain reaction (PCR) studies to
characterize packaging and segment abundance of Microplitis demolitor bracovirus
(MdBV). Like other PDVs, MdBV replicates in the ovaries of females where virions
accumulate to form a suspension called calyx fluid. Wasps then inject a quantity
of calyx fluid when ovipositing into hosts. The MdBV genome consists of 15
segments that range from 3.6 (segment A) to 34.3 kb (segment O). EM analysis
indicated that MdBV virions contain a single nucleocapsid that encapsidates one
circular DNA of variable size. We developed a semi-quantitative real-time PCR
assay using SYBR Green I. This assay indicated that five (J, O, H, N and B)
segments of the MdBV genome accounted for more than 60% of the viral DNAs in
calyx fluid. Estimates of relative segment abundance using our real-time PCR
assay were also very similar to DNA size distributions determined from
micrographs. Analysis of parasitized Pseudoplusia includens larvae indicated that
copy number of MdBV segments C, B and J varied between hosts but their relative
abundance within a host was virtually identical to their abundance in calyx
fluid. Among-tissue assays indicated that each viral segment was most abundant in
hemocytes and least abundant in salivary glands. However, the relative abundance
of each segment to one another was similar in all tissues. We also found no clear
relationship between MdBV segment and transcript abundance in hemocytes and fat
body.
PMID- 17034829
TI - Deployment of visual attention before sequences of goal-directed hand movements.
AB - We examined the allocation of attention during the preparation of sequences of
manual pointing movements in a dual task paradigm. As the primary task, the
participants had to perform a sequence of two or three reaching movements to
targets arranged on a clock face. The secondary task was a 2AFC discrimination
task in which a discrimination target (digital 'E' or '3') was presented among
distractors either at one of the movement goals or at any other position. The
data show that discrimination performance is superior at the location of all
movement targets while it is close to chance at the positions that were not
relevant for the movement. Moreover, our findings demonstrate that all movement
relevant locations are selected in parallel rather than serially in time, and
that selection involves spatially distinct, non-contiguous foci of visual
attention. We conclude that during movement preparation--well before the actual
execution of the hand movement--attention is allocated in parallel to each of the
individual movement targets.
PMID- 17034830
TI - Cellular pattern formation during retinal regeneration: a role for homotypic
control of cell fate acquisition.
AB - A dominant mechanism of cellular patterning in the growing fish retina is control
of cell fate acquisition by negative feedback signals arising from differentiated
cells. We tested the ability of a computational model of this pattern formation
mechanism to simulate cellular patterns in regenerated goldfish retina. The model
successfully simulated quantitative features of in vivo regenerated patterns,
indicating that regenerating retina has access to and utilizes patterning
mechanisms that are operational during normal growth. The atypical patterns of
regenerated retina could arise in part from regenerative progenitors that,
compared to normal growth progenitors, are less responsive to the feedback
patterning signals.
PMID- 17034831
TI - The direction aftereffect is driven by adaptation of local motion detectors.
AB - The processing of motion information by the visual system can be decomposed into
two general stages; point-by-point local motion extraction, followed by global
motion extraction through the pooling of the local motion signals. The direction
aftereffect (DAE) is a well known phenomenon in which prior adaptation to a
unidirectional moving pattern results in an exaggerated perceived direction
difference between the adapted direction and a subsequently viewed stimulus
moving in a different direction. The experiments in this paper sought to identify
where the adaptation underlying the DAE occurs within the motion processing
hierarchy. We found that the DAE exhibits interocular transfer, thus
demonstrating that the underlying adapted neural mechanisms are binocularly
driven and must, therefore, reside in the visual cortex. The remaining
experiments measured the speed tuning of the DAE, and used the derived function
to test a number of local and global models of the phenomenon. Our data provide
compelling evidence that the DAE is driven by the adaptation of motion-sensitive
neurons at the local-processing stage of motion encoding. This is in contrast to
earlier research showing that direction repulsion, which can be viewed as a
simultaneous presentation counterpart to the DAE, is a global motion process.
This leads us to conclude that the DAE and direction repulsion reflect
interactions between motion-sensitive neural mechanisms at different levels of
the motion-processing hierarchy.
PMID- 17034832
TI - Exclusion failure does not demonstrate unconscious perception II: evidence from a
forced-choice exclusion task.
AB - Systematic failure to perform exclusion (making a response that opposes the
participant's natural inclinations) for briefly displayed, masked words has been
interpreted as evidence of unconscious perception. The present study required
participants to make a forced-choice exclusion after viewing masked word targets.
The forced-choice exclusion task was properly performed in all experiments, in
contrast to previous studies that have utilized stem-completion as a dependent
variable. The exclusion failure effects interpreted as unconscious perception in
earlier studies appear to be caused by an insensitive dependent variable (stem
completion) rather than unconscious perception.
PMID- 17034833
TI - Perceptual filling-in from the edge of the blind spot.
AB - Looking at the world with one eye, we do not notice a scotoma in the receptor
free area of the visual field where the optic nerve leaves the eye. Rather we
perceive the brightness, color, and texture of the adjacent area as if they were
actually there. The mechanisms underlying this kind of perceptual filling-in
remain controversial. To better understand these processes, we determined the
minimum region around the blind spot that needs to be stimulated for filling-in
by carefully mapping the blind spot and presenting individually fitted stimulus
frames of different width around it. Uniform filling-in was observed with frame
widths as narrow as 0.05 degrees visual angle for color and 0.2 degrees for
texture. Filling-in was incomplete, when the frame was no longer contiguous with
the blind spot border due to an eye movement. These results are consistent with
the idea that perceptual filling-in of the blind spot depends on local processes
generated at the physiological edge of the cortical representation.
PMID- 17034834
TI - Arsenic in soils and plants of woodland regenerated on an arsenic-contaminated
substrate: a sustainable natural remediation?
AB - Plant As accumulation at three As-polluted sites where spontaneous re-vegetation
has taken place is examined. Each site had a different source of soil As (coal
fly ash, LeBlanc process waste, canal dredging). Plant analysis indicates that
soil-plant As transfer is poor at each site. Any mobile As is retained in root
tissues, with little transfer to shoots. Bryophytes, pteridophytes, herbaceous
and woody plants sampled at each site predominantly showed As concentrations of
<3 mg kg(-1) dry wt, whilst total soil As ranged between 50 and 220 mg kg(-1) dry
wt. Risk associated with food chain transfer at these sites is low when compared
to other routes such as direct ingestion/inhalation of As-contaminated
particulates re-entrained from an unvegetated or unstable substrate.
PMID- 17034835
TI - Evidence of hypercoagulability and inflammation in young patients long after
acute cerebral ischaemia.
AB - INTRODUCTION: Young subjects with acute cerebral ischaemia - stroke or transient
ischaemic attack - form an etiologically heterogeneous and often not clearly
explained group of patients. The aim was to investigate possible disturbances in
haemostasis and inflammation long after an acute cerebral ischaemic event.
MATERIALS AND METHODS: Forty-four consecutive patients referred after having
suffered from acute cerebral ischaemia before the age of 45 participated 1 to 9
years (median value 5 years) after the event. At the time of blood sampling 33
(75%) patients were receiving antithrombotic treatment. Forty-six apparently
healthy subjects of the same age group served as controls. In all subjects global
haemostasis parameters (overall haemostasis, coagulation and fibrinolytic
potential), thrombophilia, several markers of haemostasis activation and
inflammation were determined. RESULTS: Patients did not differ from controls in
most of the conventional risk factors and the presence of most forms of
thrombophilia, although in seven (17.5%) patients the weak presence of lupus
anticoagulants was observed. Patients had significantly increased overall
haemostasis and coagulation potential, increased soluble P-selectin and D-dimer,
decreased overall fibrinolysis potential and increased fibrinogen and C-reactive
protein compared to controls. The subgroups of patients receiving antiplatelet
treatment, with thrombophilia and recurrent acute cerebral ischaemia, did not
differ significantly from the other patients. CONCLUSIONS: In young patients long
after acute cerebral ischaemia an imbalance in the haemostatic system and a
minor, but significant degree of inflammation was detected. The mechanisms behind
haemostatic imbalance seem to be enhanced thrombin generation, platelet
activation and depressed fibrinolysis.
PMID- 17034836
TI - Caspase 9 is decreased in psoriatic epidermis.
AB - Psoriasis is a proliferative and inflammatory disease of the skin. Caspase 9 is
responsible for initiating the caspase activation cascade during apoptosis.
Apoptosis is a physiological mechanism of homeostasis and development, and
caspases are the executioners of apoptosis. This study reports the
immunohistochemical localisation of caspase 9 in psoriatic skin and compares it
with that seen in normal, healthy control skin. Skin biopsy specimens of lesions
were obtained from 15 patients with plaque type psoriasis vulgaris. The specimens
were labelled immunohistochemically for binding of an anti-caspase 9 primary
antibody. Biopsies of healthy skin from 10 age-matched and sex-matched healthy
control individuals were also analysed. The caspase 9 positive cell fraction was
calculated for both epidermal and dermal cells in psoriatic lesions and healthy
control skin. Counts of caspase 9 positive cells from the epidermis of psoriatic
skin lesions were significantly lower than those seen in healthy skin (p<0.05).
The caspase 9 immunolabelled perivascular cell counts in the dermis were not
statistically significantly different in psoriatic lesions versus normal skin
(p>0.05). Psoriatic epidermis contains little of the apoptotic marker, caspase 9.
The results of this study are indicative of decreased apoptosis in psoriatic
epidermis, and no change in the perivascular area in psoriatic lesions. These
findings support the idea that decreased apoptosis is seen in psoriatic epidermal
cells. Greater understanding of the nature of the disease may open new avenues
for further therapeutic modalities.
PMID- 17034837
TI - Synchronous ovarian granulosa cell tumor and uterine serous carcinoma: a rare
association of a high-risk endometrial cancer with anestrogenic ovarian tumor.
AB - BACKGROUND: Ovarian granulosa cell tumors are often associated with endometrial
hyperplasia or carcinoma. The endometrial carcinoma is thought to occur under the
influence of the estrogen receptor pathway and is typically a low-grade, low
stage endometrioid adenocarcinoma. CASE: We present a case of a woman with a
granulosa cell tumor of the ovary and a synchronous serous carcinoma of the
endometrium. Immunohistochemical stains for estrogen receptors, progesterone
receptors, and p53 protein were performed on both tumors. CONCLUSIONS: Not all
uterine tumors associated with ovarian granulosa cell tumors have low-risk
histology. Preoperative evaluation of the uterus with attention to tumor
subtyping is important for optimum staging and therapy.
PMID- 17034838
TI - Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial
ovarian cancer.
AB - OBJECTIVE: We investigated the expression of matrix metalloproteinase-9 (MMP-9)
and its relation to clinicopathologic factors and survival and also to previously
analyzed expressions of CD44 and hyaluronan in epithelial ovarian cancer.
METHODS: The expression of MMP-9 was analyzed immunohistochemically in 292
primary tumors and their 31 metastases. RESULTS: A low proportion of strong MMP-9
expression in cancer cells and high stromal MMP-9 expression correlated with
advanced stage of the tumor (p=0.003, p=0.02, respectively). Stromal MMP-9
expression significantly correlated with hyaluronan positivity (p<0.0005),
whereas MMP-9 did not correlate with CD44. In univariate analysis, a longer 10
year disease-related survival (DRS) was found in patients with a high proportion
of MMP-9 or strong MMP-9 expression in cancer cells (p=0.02, p=0.05,
respectively). However, high stromal expression of MMP-9 indicated short DRS
(p=0.01). In multivariate analysis of all patients, MMP-9 expressing cancer or
stromal cells were not independent prognostic factors, while in FIGO stage I
patients a high percentage of MMP-9 positive cancer cells was associated with
long DRS (p=0.008). CONCLUSION: These data suggest that MMP-9 has a dual role in
tumor progression, acting against tumor advancement when in tumor epithelium and
promoting tumor progression while in the stroma.
PMID- 17034839
TI - Relevant molecular markers and targets.
AB - Ovarian cancer is a heterogeneous disease with extensive cytogenetic and
molecular heterogeneity including aneuploidy, chromosomal alterations, mutations
and overexpression as well as a natural propensity to disseminate and spread,
making it difficult to diagnose at an early stage. Insights into the molecular
mechanisms operative in cancer development, progression and metastasis have
uncovered a wide array of targets for therapeutic intervention. In the absence of
a common driving oncogene in ovarian cancer, single targeted therapy for this
disease is unlikely to yield significant clinical benefit. Tailored approaches
that combine molecular targeting agents with cytotoxic regimens hold great
promise when used in primary treatment, during consolidation and maintenance
therapy, and in the treatment of persistent or recurrent disease. The most
promising treatment strategies are those that target the drivers of tumorigenesis
and enhance the activity of cytotoxic agents. Receptor tyrosine kinases, non
receptor tyrosine kinases, serine/threonine kinases, transferases, proteases and
deacetylases are among the relevant molecular markers and targets for ovarian
cancer that are discussed. Collaboration, coordination, creativity and aggressive
outreach to patients and their advocates are essential for success in running the
concurrent trials with multiple clinical end points and embedded translational
research that are needed to evaluate the array of promising targeted therapeutics
and combinations. Validated biomarkers, surrogate specimens and end points, and
additional clinically relevant in vitro and in vivo models for ovarian cancer are
needed to facilitate the drug development and evaluation process, and ultimately
to make meaningful improvements in the diagnosis, prevention and management of
ovarian cancer.
PMID- 17034840
TI - The effects of chronic valproate and diazepam in a mouse model of posttraumatic
stress disorder.
AB - To better understand neurochemical and psychopharmacological aspects of post
traumatic stress disorder (PTSD), it is necessary establish an animal model of
PTSD in which behavioral changes persist for a long time after the initial
traumatization. The present study aimed to characterize long-term behavioral
alterations in male ICR mice as an animal model of PTSD consisting of a 2-day
foot shock (0.8 mA, 10 s) followed by 3 weekly situational reminders (SR), and to
evaluate the effects of repeated administration of valproate and diazepam on
behavioral deficits of this animal model. The results showed that the aversive
procedure induced several long-term behavioral deficiencies: increased freezing
behavior and anxiety level, reduced time spent in an aversive like context.
Repeated treatment with valproate (100-400 mg/kg, i.p.) induced a dose-dependent
reduction of these behavioral changes. In contrast, diazepam at a low dose (0.25
mg/kg) but not at a high dose (4 mg/kg) reduced the behavioral deficiencies.
These results demonstrate that exposure to intense foot shock associated with
repeated situational reminders elicits long-term disturbances that last about 4
weeks after the foot shock exposure. These behavioral deficits can be ameliorated
by repeated administration of valproate or diazepam at some special dose ranges.
PMID- 17034841
TI - Effect of sperm numbers and concentration on sperm transport and uterine
inflammatory response in the mare.
AB - Our objective was to determine whether the concentration of cooled sperm
inseminated influenced sperm transport and intensity of the uterine inflammatory
reaction 2, 4 and 24h after insemination. Experimental subjects were 189 estrous
mares with a dominant follicle > or =35 mm in diameter and no bacterial growth or
neutrophils detected in uterine smears. Each mare was randomly assigned to
receive one of the following intrauterine treatments (volume, 20 mL):
insemination with 5x10(6) mL(-1) or 25x10(6) mL(-1) or 50x10(6) mL(-1) sperm
diluted in 3 mL seminal plasma (SP) and 17 mL skim milk; seminal plasma or skim
milk extender. Mares in a control group received no intrauterine treatment. Mares
were slaughtered 2, 4 or 24h after insemination or infusion. Oviducts were
separated from the uterus, and uterus and oviducts were then flushed with
phosphate-buffered saline (PBS). After flushing, an endometrial sample was
collected for further histopathological examination. The grade of uterine
fibrosis and the amount of neutrophils in the stratum compactum were evaluated. A
sample of each tubal flushing was examined for sperm count, and a sample of each
uterine flushing was examined for PMN count. It was concluded that compounds in
the insemination dose provoked a uterine inflammatory response, which was more
rapid and intense as sperm concentration increased. In contrast, sperm transport
through 4h after insemination was not influenced by sperm concentration.
PMID- 17034842
TI - Birth of offspring of pre-determined sex after artificial insemination of frozen
thawed, sex-sorted and re-frozen-thawed ram spermatozoa.
AB - The fertility of ram spermatozoa cryopreserved prior to, and following, sex
sorting by flow cytometry was assessed after insemination of mature Merino ewes
at a synchronised estrus. Ewes were inseminated with spermatozoa from three rams,
split into four treatment groups: 50 x 10(6) motile non-sorted, frozen-thawed
(Control50), 15 x 10(6) motile non-sorted, frozen-thawed (Control15), 15 x 10(6)
motile sex-sorted, frozen-thawed (SF15) or 15 x 10(6) motile frozen-thawed, sex
sorted, re-frozen-thawed (FSF15) ram spermatozoa. Separation of SF15 and FSF15
treatments into X- and Y-chromosome-bearing populations was achieved using a high
speed sperm sorter. The percentage of ewes lambing after insemination was similar
for Control15 (36/74; 48.6%), SF15 (35/76; 46.1%) and FSF15 (26/72; 36.1%) groups
(P>0.05). A higher percentage of ewes produced lambs in the Control50 (38/70;
54.3%) than the FSF15 group (P<0.05). Fifty-one of the 55 (92.7%) lambs derived
from fresh, sex-sorted frozen-thawed spermatozoa were of the predicted sex, as
were 41/43 (95.3%) lambs derived from frozen-thawed, sex-sorted, re-frozen-thawed
spermatozoa. This study demonstrated for the first time in any species that
frozen-thawed spermatozoa, after sex-sorting and a second cryopreservation step,
are capable of producing offspring of the predicted sex following artificial
insemination.
PMID- 17034843
TI - Relationships among predatory fish, sea urchins and barrens in Mediterranean
rocky reefs across a latitudinal gradient.
AB - Previous studies conducted on a local scale emphasised the potential of trophic
cascades in Mediterranean rocky reefs (involving predatory fish, sea urchins and
macroalgae) in affecting the transition between benthic communities dominated by
erected macroalgae and barrens (i.e., bare rock with partial cover of encrusting
algae). Distribution patterns of fish predators of sea urchins (Diplodus sargus
sargus, Diplodus vulgaris, Coris julis and Thalassoma pavo), sea urchins
(Paracentrotus lividus and Arbacia lixula) and barrens, and fish predation rates
upon sea urchins, were assessed in shallow (3-6m depth) sublittoral rocky reefs
in the northern, central and southern sectors of the eastern Adriatic Sea, i.e.,
on a large spatial scale of hundreds of kilometres. No dramatic differences were
observed in predatory fish density across latitude, except for a lower density of
small D. sargus sargus in the northern Adriatic and an increasing density of T.
pavo from north to south. P. lividus did not show any significant difference
across latitude, whereas A. lixula was more abundant in the southern than in the
central Adriatic. Barrens were more extended in the southern than in the central
and northern sectors, and were related with sea urchin density. Fish predation
upon adult sea urchins did not change on a large scale, whereas it was slightly
higher in the southern sector for juveniles when predation rates of both urchins
were pooled. Results show that: (1) assemblages of predatory fish and sea
urchins, and barren extent change across latitude in the eastern Adriatic Sea,
(2) the weak relations between predatory fish density and predation rates on
urchins reveal that factors other than top-down control can be important over
large scale (with the caveat that the study was conducted in fished areas) and
(3) patterns of interaction among strongly interacting taxa could change on large
spatial scales and the number of species involved.
PMID- 17034844
TI - A biodegradable poly(ester amine) based on polycaprolactone and polyethylenimine
as a gene carrier.
AB - The aim of research was to develop and optimize delivery systems for plasmid DNA
(pDNA) based on biodegradable polymers, in particular, poly(ester amine)s (PEAs),
suitable for non-viral gene therapy. Poly(ester amine)s were successfully
synthesized by Michael addition reaction between polycaprolactone (PCL)
diacrylate and low molecular weight polyethylenimine (PEI). PEA/DNA complexes
showed effective and stable DNA condensation with the particle sizes below 200nm,
implicating its potential for intracellular delivery. PEAs showed controlled
degradation and were essentially non-toxic in all three cells (293T: Human kidney
carcinoma, HepG2: Human hepatoblastoma and HeLa: Human cervix epithelial
carcinoma cell lines) at higher doses in contrast to PEI 25K. PEAs also revealed
much higher transfection efficiencies in three cell lines as compared to PEI 25K.
The highest reporter gene expression was observed for PCL/PEI-1.2 (MW 1200)
complex having transfection efficiency 15-25 folds higher than PEI 25K in vitro.
Also PEA/DNA complexes successfully transfected cells in vivo after aerosol
administration than PEI 25K. These PEAs can be used as most efficient polymeric
vectors which provide a versatile platform for further investigation of structure
property relationship along with the controlled degradation, significant low
cytotoxicity and high transfection efficiency.
PMID- 17034845
TI - In vitro fatigue-crack growth and fracture toughness behavior of thin-walled
superelastic Nitinol tube for endovascular stents: A basis for defining the
effect of crack-like defects.
AB - Endovascular stents made of the superelastic nickel-titanium alloy Nitinol are
subjected in service to tens of millions of loading cycles and even "single
event" overloads, both of which can potentially result in fracture and/or
complete failure of the device. A fracture-mechanics-based methodology can
provide a means to quantify relevant material parameters critical to the design
against such failures. However, there is a dearth of relevant experimental data
in the literature on such fracture-mechanics-based approaches to fatigue in
Nitinol; furthermore, that which does exist invariably pertains to product forms
that are not appropriate for stent manufacture, e.g., bulk Nitinol bar and strip.
Consequently, the current work is focused on characterizing in vitro both
subcritical and critical crack growth (fatigue-crack growth and R-curve fracture
toughness) behavior in thin-walled ( approximately 400microm thick) Nitinol
tubing similar to that used for medical device manufacture (following shape
setting procedures to flatten the material), with a resultant austenite finish
temperature of A(f) approximately 25-30 degrees C, identical to self-expanding
Nitinol stents. Fatigue-crack growth behavior, measured in Hanks' Balanced Saline
Solution over a wide spectrum of growth rates (down to 10(-10)m/cycle) and at a
range of positive load ratios (R=0.1-0.7), revealed significantly higher fatigue
thresholds than had been previously reported for bulk Nitinol material. In
addition, we examine the critical effect of test frequency, as most fatigue
experiments on Nitinol have been performed at 30Hz or above, despite the fact
that this is far in excess of the frequency of physiological loading. Finally,
the fracture toughness properties are characterized in thin-section Nitinol and
show marked crack-resistance (R-curve) behavior with a dependence on crack-growth
angle (with respect to the tube drawing axis); additionally, measured toughnesses
are found to be lower than has been previously reported for bulk Nitinol.
PMID- 17034846
TI - Engineered matrix coatings to modulate the adhesion of CD133+ human hematopoietic
progenitor cells.
AB - Interactions of hematopoietic progenitor cells (HPC) with their local
microenvironments in the bone marrow are thought to control homing,
differentiation, and self-renewal of the cells. To dissect the role of
extracellular matrix (ECM) components of the niche microenvironment, a set of
well-defined ECM coatings including fibronectin, heparin, heparan sulphate,
hyaluronic acid, tropocollagen I, and co-fibrils of collagen I with heparin or
hyaluronic acid was prepared and analysed with respect to the attachment of human
CD133+ HPC in vitro. The extension of the adhesion areas of individual cells as
well as the fraction of adherent cells were assessed by reflection interference
contrast microscopy (RICM). Intense cell-matrix interactions were found on
surfaces coated with fibronectin, heparin, heparan sulphate, and on the collagen
I based co-fibrils. Insignificant adhesion was found for tropocollagen I and
hyaluronic acid. The strongest adhesion of HPC was observed on fibronectin with
contact areas of about 7 microm(2). Interaction of HPC with coatings consisting
of heparin, heparan sulphate, and co-fibrils result in small circular shaped
contact zones of 3 microm(2) pointing to another, less efficient, adhesion
mechanism. Analysing the specificity of cell-matrix interaction by antibody
blocking experiments suggests an integrin(alpha(5)beta(1))-specific adhesion on
fibronectin, while adhesion on heparin was shown to be mediated by selectins
(CD62L). Taken together, our data provide a basis for the design of advanced
culture carriers supporting site-specific proliferation or differentiation of
HPC.
PMID- 17034847
TI - The effect of gradually graded shear stress on the morphological integrity of a
huvec-seeded compliant small-diameter vascular graft.
AB - The premature endothelialization of tissue-engineered grafts had often induced
cellular detachment at an early period of implantation in arterial circulation,
resulting in occlusion at an early period of implantation. This study was aimed
to determine whether gradually increased shear stress applied ex vivo improves
cell retention and tissue morphological integrity including cell shape and
alignment, actin fiber alignment and expression of vascular endothelial (VE)
cadherin. Tissue-engineered grafts used for this study were human umbilical vein
endothelial cell (HUVEC)-seeded compliant small-diameter grafts made of poly(L
lactide-co-epsilon-caprolactone) fiber meshes fabricated by electrospinning. The
shear stresses applied to grafts, generated using a custom-designed mock
circulatory apparatus, were 3.2, 8.7 and 19.6 dyn/cm(2). The grafts completely
monolayered prior to shear stress exposure exhibited a polygonal cobblestone
morphology with randomly distributed actin fibers and VE cadherin at the
continuous peripheral region of adjacent cells. The 24-h-loading of high shear
stresses (8.7 and 19.6 dyn/cm(2)) equivalent to those of the arterial circulatory
system resulted in severe cellular damage resulting in the complete loss of
cells. However, a gradually increased graded exposure from a low (3.2 dyn/cm(2))
to a high shear stress (19.6 dyn/cm(2)) resulted in a markedly reduced cell
detachment, a highly elongated cell shape, and orientation or alignment of both
cells and actin fibers, which were parallel to the direction of flow. Although VE
cadherin expression was not detected yet, a higher degree of tissue integrity was
achieved, which may greatly improve the performance particularly at an early
period of implantation.
PMID- 17034848
TI - Absolute quantification of gene expression in biomaterials research using real
time PCR.
AB - One major measurement of tissue-engineered constructs efficacy and performance is
determining expression levels of genes of interest at the molecular level. This
measurement is commonly carried out with reverse transcription-polymerase chain
reaction (RT-PCR). In this study, we described a novel method in achieving
absolute quantification of gene expression using real-time PCR (aqPCR). This
novel method did not require molecular cloning steps to prepare the standards for
quantification comparison. Standards were linear double-stranded DNA molecules
instead of the typical gene-in-plasmid format. aqPCR could also be used to give
relative quantification comparisons between samples simply by dividing the copy
numbers readings of the gene of interest with that of the normalization gene. RNA
was extracted from monolayer and from polycaprolactone scaffold cultures and
assayed for beta-actin and osteocalcin genes. We compared our aqPCR method with
end-point PCR since end-point PCR is still a common means of measuring gene
expression in the biomaterials field. This study showed that aqPCR was a better
method to quantify gene expression than end-point PCR. With our described linear
DNA standards method, we were able to obtain not only relative quantification of
osteocalcin and beta-actin expression level but also actual copy numbers of
osteocalcin and beta-actin for the monolayer culture and to be 1.34 x 10(4) and
1.45 x 10(7) copies, respectively and for the scaffold cultures to be 772 and
2.83 x 10(5) copies, respectively per starting total RNA mass of 10 ng. The
standards curves made from these linear DNA standards showed good linearity
(R(2)=0.9964 and 0.9902 for osteocalcin and beta-actin standards graphs), ranged
from 10 to 10(9) copies and of comparable accuracy to current absolute
quantification real-time PCR methods (which used plasmid standards obtained
through molecular cloning methods). Our method might be a viable and more user
friendly alternative to current absolute quantification real-time PCR protocols.
PMID- 17034849
TI - Calcium signaling complexes in microdomains of polarized secretory cells.
AB - The highly polarized nature of epithelial cells in exocrine glands necessitates
targeting, assembly into complexes and confinement of the molecules comprising
the Ca(2+) signaling apparatus, to cellular microdomains. Such high degree of
polarized localization has been shown for all Ca(2+) signaling molecules tested,
including G protein coupled receptors and their associated proteins, Ca(2+)
pumps, Ca(2+) influx channels at the plasma membrane and Ca(2+) release channels
in the endoplasmic reticulum. Although the physiological significance of
polarized Ca(2+) signaling is clear, little is known about the mechanism of
targeting, assembly and retention of Ca(2+) signaling complexes in cellular
microdomains. The present review attempts to summarize the evidence in favor of
polarized expression of Ca(2+) signaling proteins at the apical pole of secretory
cells with emphasis on the role of scaffolding proteins in the assembly and
function of the Ca(2+) signaling complexes. The consequence of polarized
enrichment of Ca(2+) signaling complexes at the apical pole is generation of an
apical to basal pole gradient of cell responsiveness that, at low physiological
agonist concentrations, limits Ca(2+) spikes to the apical pole, and when a
Ca(2+) wave occurs, it always propagates from the apical to the basal pole. Our
understanding of Ca(2+) signaling in microdomains is likely to increase rapidly
with the application of techniques to controllably and selectively disrupt
components of the complexes and apply high resolution recording techniques, such
as TIRF microscopy to this problem.
PMID- 17034850
TI - Calcium microdomains and gene expression in neurons and skeletal muscle cells.
AB - Neurons generate particular calcium microdomains in response to different
stimuli. Calcium microdomains have a central role in a variety of neuronal
functions. In particular, calcium microdomains participate in long-lasting
synaptic plasticity--a neuronal response presumably correlated with cognitive
brain functions that requires expression of new gene products. Stimulation of
skeletal muscle generates - with few milliseconds delay - calcium microdomains
that have a central role in the ensuing muscle contraction. In addition, recent
evidence indicates that sustained stimulation of skeletal muscle cells in culture
generates calcium microdomains, which stimulate gene expression but not muscle
contraction. The mechanisms whereby calcium microdomains activate signaling
cascades that lead to the transcription of genes known to participate in specific
cellular responses are the central topic of this review. Thus, we will discuss
here the signaling pathways and molecular mechanisms, which via activation of
particular calcium-dependent transcription factors regulate the expression of
specific genes or set of genes in neurons or skeletal muscle cells.
PMID- 17034851
TI - Vector-based RNAi approach to isoform-specific downregulation of vascular
endothelial growth factor (VEGF)165 expression in human leukemia cells.
AB - Vascular endothelial growth factor (VEGF) plays a critical role during normal
embryonic angiogenesis and also in the pathological angiogenesis that occurs in a
number of diseases, including cancer. K562 human leukemia cells overexpress VEGF,
with a shift in isoform production from membrane-bound VEGF189 to the more
soluble VEGF165. In the present study, three 19 bp reverse repeated motifs
targeting exons 5 and 7 boundary of VEGF165 gene sequence with 9 bp spacer were
synthesized and cloned into eukaryotic expression plasmid pGenesil-1 containing
U6 shRNA promoter and termination signal of RNA polymerase. The recombinant
plasmids pGenesil-VR1, pGenesil-VR2, pGenesil-VR3 and pGenesil-con (plasmid
containing random DNA fragment) were transfected into K562 cells, respectively,
through lipofectamine reagent. A vector-based small interfering RNA(SiRNA)
inhibited VEGF165 mRNA expression by 72% and protein production by 67% in K562
cells. Human microvascular endothelial cell migration induced by conditioned
medium from VEGFsi-transfected K562 cells was significantly less than that
induced by conditioned medium from K562 cells and control vector-transfected K562
cells. Furthermore, the VEGF shRNA dramatically suppressed tumor angiogenesis and
tumor growth in a K562 s.c. xenograft model. Vessel density as assessed by vWF
immunohistochemical analysis was also decreased. This strategy provides a novel
tool to study the function of various VEGF isoforms and may contribute to VEGF
specific treatment in cancer.
PMID- 17034852
TI - [Evaluation of a group intervention using a feminist approach for women
experiencing sexual abuse].
AB - OBJECTIVE: The present study evaluates a group intervention using a feminist
approach for women experiencing sexual abuse in childhood or adulthood in order
to measure changes associated with participation in a group intervention and
verifies whether effects are maintained over time. The present study relates
effects of the group intervention in terms of psychological distress, depression
symptoms, post-traumatic stress symptoms and feelings of guilt and helplessness.
METHOD: The sample consists of 26 women participating in a group intervention
offered by sexual assault centers in Quebec (CALACS - Centre d'aide et de lutte
contre les agressions a caractere sexuel). RESULTS: Results show significant
differences between pretest and post-test scores obtained one week following the
end of the group intervention and gains are maintained at follow-up 3 months
later. CONCLUSION: The findings suggest that participation in the group
intervention is associated with a reduction of psychological distress, depression
symptoms, post-traumatic stress symptoms and feelings of guilt and helplessness
in adult women reporting sexual abuse.
PMID- 17034853
TI - Real-time gene expression analysis in carp (Cyprinus carpio L.) skin:
inflammatory responses to injury mimicking infection with ectoparasites.
AB - We studied a predictive model of gene expression induced by mechanical injury of
fish skin, to resolve the confounding effects on the immune system induced by
injury and skin parasite-specific molecules. We applied real time quantitative
PCR (RQ-PCR) to measure the expression of the pro-inflammatory cytokines CXCa,
CXCb, interleukin (IL)1-beta, tumor necrosis factor alpha (TNFalpha), and the
receptors IL1R1, CXCR1 and CXCR2 in skin of Cyprinus carpio after mechanical
injury. We also studied the expression of the anti-inflammatory cytokine IL-10.
Most obvious, specific up-regulation of the chemokine CXCa, the chemokine
receptor CXCR1 and the pro-inflammatory cytokine IL-beta was detected at 2-3h
after injury. In order to correlate gene expression patterns after injury with
cell migration, we studied chemotaxis of head kidney leukocytes towards lysates
of epithelioma papulosum cyprini (EPC) cells. Neutrophilic granulocytes were
shown to migrate towards epithelial lysates. Using immunohistochemistry we
observed that the early inflammatory response after injury involved an influx of
cells, most probably neutrophilic granulocytes, into the injured area. This
suggests that the increased expression of pro-inflammatory genes is related to a
rapid influx of neutrophilic granulocytes.
PMID- 17034854
TI - Lipophilicity parameters for ionic liquid cations and their correlation to in
vitro cytotoxicity.
AB - Regarding the great structural variability of the currently expanding group of
ionic liquids, it is highly desirable to understand the basic factors affecting
their toxicity in different biological systems. The present study of a set of 74
ionic liquids with imidazolium, pyrrolidinium, pyridinium, quinolinium,
quaternary phosphonium and quaternary ammonium cations and the comparatively
small anions Cl(-), Br(-), BF(4)(-), or PF(6)(-) demonstrates the influence of
the cation lipophilicity on the cytotoxicity in IPC-81 leukemia cells from rats.
The scope of this correlation is limited to ionic liquids with these or similarly
small anions that are sufficiently nonreactive under physiological and
chromatographic conditions and whose cation lipophilicity does not exceed a
certain threshold.
PMID- 17034855
TI - Occurrence of Bifidobacterium in the intestine of newborns by fluorescence in
situ hybridization.
AB - Colonization by Bifidobacterium occurs generally within 4 days of life. The new
method FISH has been applied for molecular detection of Bifidobacteria. The study
was carried out on 26 healthy newborns delivered by vaginal delivery. Breast-fed
infants harbor a gastrointestinal flora characterized by an increased
concentration of Bifidobacterium cells (by a factor of 1.75). In artificial
alimentation, some infants either did not harbor any Bifidobacterium or showed
lower numbers of Bifidobacterium. Moreover, male newborns show higher numbers of
Bifidobacterium, but in both sexes the predominance of Bifidobacterium is evident
after maternal alimentation.
PMID- 17034856
TI - Seroepidemiological survey of Rhodoccocus equi infection in asymptomatic horses
from Bursa, Izmir and Istanbul provinces, Turkey.
AB - In order to assess the Rhodococcus equi infection in three provinces of Turkey
(Bursa, Izmir and Istanbul), 696 sera from healthy foals and adult horses were
tested by indirect ELISA using a R. equi reference strain (ATCC 6939) as antigen.
103 sera (14.80%) with titres >0.646 resulted positive. Seroprevalence was
significantly higher (P=0.0053) in male than in female horses of Istanbul
province, although higher antibody titres (mean value) were observed in the
female group of Bursa and Izmir provinces with differences estimated between
provinces (P=0.0002). Seroprevalence was correlated with age: foals aged less
than 1 year (P<10(-4)) and horses from 5 to 10 years old (P=0.018) resulted more
infected in Bursa and Izmir provinces. Our findings indicate that R. equi
infection actually occurs in all investigated provinces, suggesting the
importance of serological survey to diagnose the infection and to prevent the
zoonotic risk.
PMID- 17034857
TI - Immune modulation by probiotic strains: quantification of phagocytosis of
Aeromonas salmonicida by leukocytes isolated from gut of rainbow trout
(Oncorhynchus mykiss) using a radiolabelling assay.
AB - A method is described for the rapid and sensitive assay of phagocytosis that
utilizes radioactively labelled bacteria. With this method, we observed that
phagocytosis of heat-inactivated Aeromonas salmonicida by leukocytes isolated
from gut of rainbow trout fed with different viable probiotics (Lactococcus
lactis subsp. lactis, Lactobacillus sakei, and Leuconostoc mesenteroides) was
significantly higher (P<0.05) after 2 weeks of probiotic-feeding than the control
group. However, only phagocytosis of live A. salmonicida by the leukocytes
isolated from gut of rainbow trout fed with L. lactis subsp. lactis was
significantly higher (P<0.05) than the control group.
PMID- 17034858
TI - Histological studies on the ontogeny of bovine palatine and pharyngeal tonsil:
germinal center formation, IgG, and IgA mRNA expression.
AB - The development and distribution of lymphocyte subsets in calf palatine and
pharyngeal tonsil were examined. During prenatal development, B cells were
distributed in the subepithelial area, and T cells and MHC class II(+) cells were
found in the deep layer of B-cell area, respectively, in both tonsils. At
neonatal stage, lymphoid follicle containing a few CD4(+) cells have been formed
in both tonsils. IgG(+) and IgA(+) cells were found in the parafollicular and
epithelial area. At 3 months old, many germinal centers were recognized in both
tonsils. CD4(+) cells and IgG mRNA expression were detected in light zone of
germinal centers. Many IgG, and IgA mRNA expressions also could be detected in
the parafollicular and subepithelial area of both tonsils. The data suggest that
both tonsils have an important role of local immune defense against invading
antigen after birth. The comparison of the histological characteristics of tonsil
and Peyer's patch during ontogeny is also discussed.
PMID- 17034859
TI - Porcine interleukin-2 gene encapsulated in chitosan nanoparticles enhances immune
response of mice to piglet paratyphoid vaccine.
AB - Interleukin-2 (IL-2) is vital to elicit and amplify the cellular and humoral
immune responses to foreign antigens, which is extensively utilized in the
control of infectious disease and treatment of various cancers. Porcine and
murine IL-2 genes were, respectively, subcloned into VR1020, designated as VPIL-2
and VMIL-2, and then encapsulated in chitosan nanoparticles (CNP) prepared by
ionic linkage. The BALB/c mice were intramuscularly co-administrated with
chitosan-IL-2 nanoparticles (CNP-IL2) and paratyphoid vaccine to test the
adjuvant effect of CNP-IL2. On day 35, the immunized mice were orally challenged
with virulent Salmonella. The content of IgG, IgA, IgM, IL-2, IL-4, IL-6 and
specific antibody titer as well as the number of immunocompetent cells were
systematically analyzed in the vaccinated mice. The results revealed that the
levels of immunoglobulins, cytokines, the specific antibodies, together with the
numbers of lymphocytes significantly increased in vaccinated mice inoculated with
CNP-VPIL2 in contrast with those with naked IL-2 plasmids and blank plasmids. The
CNP-VPIL2 immunized mice exhibited higher humoral and cellular immune responses,
less severe clinical signs and lesions of disease caused by the bacteria than the
other groups after challenge. These findings suggest that CNP-VPIL2 has a
significant enhancement effect on immune responses of mice, which results in
better immunoprotection against Salmonella infection, indicating that CNP-VPIL2
could be employed as an effective immunoadjuvant to elevate immunity of animals
to conventional vaccines.
PMID- 17034860
TI - Isolation of pathogenic Listeria monocytogenes in faeces of wild animals in
captivity.
AB - The isolation of pathogenic Listeria spp. in faecal samples of captive wild
animals was studied. Isolation of the pathogen was attempted from the samples by
selective enrichment in University of Vermont Medium and plating onto Dominguez
Rodriguez isolation agar, PALCAM agar and modified McBride Listeria agar.
Pathogenicity of the isolates was tested by Christie, Atkins, Munch Petersen
test, phosphotidylinositol-specific phospholipase C assay, mice inoculation test
and chick embryo bioassay. Listeria monocytogenes was isolated from eight (16%)
of 50 faecal samples from six different mammals and one bird. Out of eight
isolates, one isolate from jackal proved to be pathogenic by all the
pathogenicity testing assays. PCR amplification of virulence genes suggested that
the isolate was potentially pathogenic.
PMID- 17034861
TI - Effect of soil properties on arsenic fractionation and bioaccessibility in cattle
and sheep dipping vat sites.
AB - Historical use of high arsenic (As) concentrations in cattle/sheep dipping vat
sites to treat ticks has resulted in severe contamination of soil and groundwater
with this Group-A human carcinogen. In the absence of a universally applicable
soil As bioaccessibility model, baseline risk assessment studies have
traditionally used the extremely conservative estimate of 100% soil As
bioaccessibility. Several in-vitro, as well as, in-vivo animal studies suggest
that As bioaccessibility in soil can be lower than that in water. Arsenic in
soils exists in several geochemical forms with varying degree of dissolution in
the human digestive system, and thus, with highly varying As bioaccessibility.
Earlier batch incubation studies with As-spiked soils have shown that As
bioaccessibility is a function of soil physicochemical properties. We selected 12
dipping vat soils collected from USA and Australia to test the hypothesis that
soil properties exert a significant effect on As bioaccessibility in As
contaminated sites. The 12 soils varied widely in terms of soil physico-chemical
properties. They were subject to an As sequential fractionation scheme and two in
vitro tests (IVGS and IVGIA) to simulate soil As bioavailability in the human
gastrointestinal system. Sequential As fractionation results showed that the
majority of the As measured in the dipping vat soils resided either in the Fe/Al
hydroxide fraction, or the Ca/Mg fractions, or in the residual fraction. Water
extractable As fraction of the 12 soils was typically <10% of the total, reaching
values up to 23%, indicating minimal leaching potential, and hence, lower risk of
As-contamination from exposure to groundwater, typically used as drinking water
in many parts of the world. Partial individual correlations and subsequent
multiple regression analyses suggested that the most significant soil factors
influencing As bioaccessibility were total Ca+Mg, total P, clay content and EC.
Collectively, these soil properties were able to explain 85 and 86% of the
variability associated with the prediction of bioaccessible As, using IVGS and
IVGIA in-vitro tests, respectively. This study showed that specific soil
properties influenced the magnitude of soil As bioaccessibility, which was
typically much lower than total soil-As concentrations, challenging the
traditional risk assessment guideline, which assumes that soil As is 100%
bioaccessible. Our study showed that total soil As concentration is unlikely to
provide an accurate estimate of human health risk from exposure to dipping vat
site soils.
PMID- 17034862
TI - Induction of interferon-gamma by Taenia crassiceps glycans and Lewis sugars in
naive BALB/c spleen and peritoneal exudate cells.
AB - Helminth parasites are known to alter host immune responses and the responsible
molecules are a potential source of biological immunoadjuvants. Previously, we
have reported strong Th-2 type immunomodulatory properties of Taenia crassiceps
glycans. In this study, we report interferon-gamma (IFN-gamma) stimulatory
activity of fractionated Taenia glycans and Lewis sugars with comparable glycan
composition. Our data show that Taenia glycans and Lewis X pentasaccharide are
potent stimulators of the Th-1 type cytokine IFN-gamma. We postulate that the
terminal beta-(1-4)-galactose residue in Lewis X is associated with IFN-gamma
stimulation from naive BALB/c mouse spleen and peritoneal exudate cells.
Antibodies to toll-like receptors (TLRs) inhibited the Lewis X-induced IFN-gamma
secretion. Lewis X up-regulated the expression of NF-kappaB p65 from naive spleen
cells and IFN-gamma transcription in peritoneal exudate cells. These data
demonstrate the ability of Lewis type helminth glycans to modulate host responses
in a Th-1 direction via NF-kappaB p65, IFN-gamma and macrophage TLRs.
PMID- 17034863
TI - An in vitro study of interactions between insulin-mimetic zinc(II) complexes and
selected plasma components.
AB - The speciations of some potent insulin-mimetic zinc(II) complexes of bidentate
ligands: maltol and 1,2-dimethyl-3-hydroxypyridinone with (O,O) and picolinic
acid with (N,O) coordination modes, were studied via solution equilibrium
investigations of the ternary complex formation in the presence of small relevant
bioligands of the blood serum such as cysteine, histidine and citric acid.
Results show that formation of the ternary complexes, especially with cysteine,
is favoured at physiological pH range in almost all systems studied. Besides
these low molecular mass binders, serum proteins among others albumin and
transferrin can bind zinc(II) or its complexes. Accordingly, the distribution of
zinc(II) between the small and high molecular mass fractions of the serum was
also studied by ultrafiltration. Modelling calculations relating to the
distribution of zinc(II), using the stability constants of the ternary complexes
studied and those of the serum proteins reported in the literature, confirmed the
ultrafiltration results, namely, the primary role of albumin in zinc(II) binding
among the low and high molecular mass components of the serum.
PMID- 17034864
TI - Reduced expression of IL-6 and IL-1alpha mRNAs in secretory phase endometrium of
women with recurrent miscarriage.
AB - A diverse array of cytokines is implicated in regulating the immune adaptation
and endometrial tissue remodelling events that facilitate successful embryo
implantation and early placental development. The aim of this study was to
evaluate expression of mRNAs encoding a panel of immunoregulatory cytokines in
the endometrium of fertile women and women experiencing recurrent miscarriage
using highly sensitive, quantitative RT-PCR assays. Endometrial biopsies were
collected during the mid-secretory phase of the menstrual cycle from women
classified as proven fertile (control; n=12) and women experiencing unexplained
recurrent miscarriage (RM; n=9). Reduced IL-6 mRNA and reduced IL-1alpha mRNA
were independently associated with recurrent miscarriage. Altered expression was
evident after accounting for variation in the composition of endometrial biopsies
by normalization of data to epithelial and mesenchymal cell-specific transcripts,
cytokeratin-18 mRNA and vimentin mRNA, respectively. The relative abundance of
mRNAs encoding LIF, GM-CSF, IFNgamma, IL-1beta, IL-4, IL-5, IL-10, IL-12p40,
TNFalpha, TGFbeta1, TGFbeta2 and TGFbeta3 were not altered in recurrent
miscarriage tissue. Associations between expression of IL-10, LIF, GM-CSF and
TGFbeta2 suggest that regulatory circuits link the transcription of these
cytokine genes. Inadequate expression of IL-6 and IL-1alpha mRNAs in endometrial
tissue may predispose to recurrent miscarriage through a perturbed maternal
immune response, effects on decidual tissue remodeling and angiogenesis, or
dysregulated trophoblast differentiation and invasion. Quantitative RT-PCR assays
for these cytokines in endometrial biopsies may be a realistic strategy for
development of novel diagnostics for predisposition to recurrent miscarriage.
PMID- 17034865
TI - Re: the role of topical nasal steroids in the treatment of children with otitis
media with effusion and/or adenoid hypertrophy.
PMID- 17034866
TI - The presentation and management of vascular rings: an otolaryngology perspective.
AB - OBJECTIVE: To review the presentation and natural history of children with
vascular rings and present management guidelines. METHODS: Retrospective study of
tertiary care pediatric medical center charts from 1991 to 2002. RESULTS: There
were 37 males and 27 females with a diagnosis of vascular rings. At presentation,
91% of patients had airway symptoms and 47% had esophageal symptoms. Airway
symptoms included stridor (63%), recurrent respiratory infections (47%),
respiratory distress (19%), and cough (17%). The most common esophageal symptom
was dysphagia (27%). Pre-operative studies included: echocardiography (96%),
chest X-ray (93%), barium swallow (75%), magnetic resonance imaging (MRI) (60%),
and computerized tomography (CT) scan of the chest (59%). Surgical management
included open (n=25) and thoracoscopic (n=39) approach. Complications included
recurrent laryngeal nerve injury in five patients (8%). CONCLUSION: Children with
vascular rings present with respiratory and/or feeding difficulty. The evaluation
should include chest X-ray, echocardiography, and barium swallow. Direct
laryngoscopy and bronchoscopy are recommended to assess the degree of compression
of the airway and/or esophagus, tracheomalacia, and vocal fold motion prior to
intervention. Indication for surgical release is given when the diagnosis is made
and can be assisted by advanced radiology studies. Surgical options include
minimally invasive techniques involving either thoracoscopic or robotic-assisted
repairs, as well as open procedures involving thoracotomy.
PMID- 17034867
TI - Purification and immunogenicity study of human papillomavirus type 16 L1 protein
in Saccharomyces cerevisiae.
AB - Human papillomavirus 16 virus-like particle (HPV16 VLP) vaccines expressed in
Saccharomyces cerevisiae are under Phase III trial and are expected to be on the
market in the near future. We have established a convenient and economical system
for the prophylactic study of vaccines derived from HPV16 VLPs, and
neutralization tests to standardize HPV serological methodology as a measure of
validation. To purify HPV16 VLPs, yeast cells expressing HPV16 L1 protein were
cultured and purified on a small scale by ultracentrifugation and size-exclusion
and cation-exchange chromatography using open columns. The highly purified HPV16
L1 protein was identified by SDS-PAGE and Western blotting, and electron
microscopic analysis confirmed that they self-assembled into VLPs. To test the
efficacy of the purified VLPs as a vaccine and their ability to induce humoral
immunity, we performed ELISA assays and observed a significant increase in the
titer of anti-HPV16 VLPs antibodies in the sera of immunized mice. High anti
HPV16 neutralizing titers were found in the sera of vaccinated mice, as measured
by a SEAP-based pseudovirus neutralization assay. These results would be useful
in the evaluation of the immunogenicity of HPV vaccine candidates, and provide an
international reference standard for HPV serological methods.
PMID- 17034868
TI - Binding kinetics, uptake and intracellular accumulation of F105, an anti-gp120
human IgG1kappa monoclonal antibody, in HIV-1 infected cells.
AB - The use of targeting moieties is a new and exciting field of scientific research
for facilitating the specific delivery of therapeutic agents in HIV-infected
patients. The interaction of a potential targeting moiety with its ligand is a
crucial factor in the evaluation of a targeted approach for chemotherapeutic
intervention. Therefore, we have further characterized the interaction between a
potential targeting agent, the monoclonal human antibody F105, and its ligand
gp120, a glycoprotein expressed on the surface of HIV-1 infected cells. We
demonstrate the specificity of binding and entry of F105 to infected cells. F105
was rapidly taken up into the cell and accumulated in the Golgi apparatus.
Kinetic analysis of the F105-gp120 interaction revealed an equilibrium
dissociation constant (K(D)) of 0.62 nM, compared with the gp120-CD4 interaction
where the K(D) was determined at 35 nM. Consequently, F105 displayed a higher
gp120 affinity. This was due to a slower dissociation as compared with the
natural ligand. These data further underline the potential of monoclonal
antibodies as targeting agents, and offer new insights into the possibility of
F105 as a targeting moiety for the delivery of antiretroviral drugs to HIV-1
infected cells.
PMID- 17034869
TI - Expression of the nucleoprotein gene of rabies virus for use as a diagnostic
reagent.
AB - The nucleoprotein (N) gene of rabies virus CTN strain, was cloned, sequenced and
expressed in Escherichia coli as a fusion with maltose binding protein (MBP). The
antigenicity of this recombinant MBP-N fusion protein was examined by Western
blotting and enzyme linked immunosorbent assay (ELISA). Subsequently, an indirect
ELISA was developed to detect rabies specific antibody levels. Using sera from
naive and vaccinated animals the ELISA results were compared with virus
neutralizing antibodies detected by a rapid fluorescent focus inhibition test
(RFFIT). Neutralizing titres by RFFIT were found to correlate well with the OD
values in the ELISA (r=0.9436) and the sensitivity and specificity of the ELISA
were shown to be 93.4 and 100%, respectively. The data indicate that the
recombinant MBP-N fusion protein can be expressed and isolated straightforwardly
and may be useful as a safe and abundant source of antigen to monitor
seropositivity in vaccinated canines.
PMID- 17034870
TI - Control of antigen mass transfer via capture substrate rotation: an absolute
method for the determination of viral pathogen concentration and reduction of
heterogeneous immunoassay incubation times.
AB - Immunosorbent assays are commonly employed as diagnostic tests in human
healthcare, veterinary medicine and bioterrorism prevention. These assays,
however, often require long incubation times, limiting sample throughput. As an
approach to overcome this weakness, this paper examines the use of rotating
capture substrates to increase the flux of antigen to the surface, thereby
reducing the incubation time. To assess the capability of this approach, porcine
parvovirus (PPV) was selectively extracted from solution by systematically
varying the rotation rate of a gold substrate modified with a layer of anti-PPV
monoclonal antibodies. The captured PPV were then directly imaged and quantified
by atomic force microscopy. The benefits of substrate rotation are demonstrated
by comparing an assay performed under stagnant conditions to one carried out with
substrate rotation at 800 rpm, both for 10 min incubations at 25 degrees C. The
use of rotation lowered the limit of detection to 3.4x10(4)TCID50/mL
(approximately 80 fM) from 3.2x10(5)TCID50/mL (approximately 800 fM) under
stagnant conditions. Results are also presented that show this strategy can be
used: (1) to determine antigen concentrations without standards and (2) to
establish the numerical relationship between quantal concentration units (e.g.,
50% tissue culture infective dose (TCID50)) and quantitative concentration units
(e.g., viruses/mL) The potential to broadly apply this technique to heterogeneous
immunoassays is also briefly discussed.
PMID- 17034871
TI - Multiplex PCR for the simultaneous detection of pseudorabies virus, porcine
cytomegalovirus, and porcine circovirus in pigs.
AB - The use of porcine organs is being developed as a means to alleviate the shortage
of human organs for transplantation. Recommendations have been published for the
microbiological specifications of organ-source pigs to reduce the possibility of
a microorganism from pigs being inadvertently transferred to the recipient of the
xenograft. The pseudorabies virus (PRV), porcine cytomegalovirus (PCMV), and
porcine circovirus (PCV) are infectious agents in pigs that are considered to be
of significance for the microbiological safety of xenotransplantation. A
multiplex polymerase chain reaction (mPCR) was developed to detect and
differentiate among PRV, PCMV, and PCV. The sensitivities of the multiplex PCR
were 10(2.5) TCID(50)/ml for PRV, 10(1.8) TCID(50)/ml for PCMV, and 10(1.8)
TCID(50)/ml for PCV. The lowest viral concentrations detected by single PCR were
10(1.5) TCID(50)/ml for PRV, 10(1.0) TCID(50)/ml for PCMV, and 10(1.4)
TCID(50)/ml for PCV2. Non-specific reactions were not observed when other
viruses, bacteria, and Vero cells were used to assess the multiplex PCR. The
multiplex PCR was effective in detecting various combinations of one or more of
these viruses in pig specimens collected for xenotransplantation.
PMID- 17034872
TI - Differential proinflammatory and angiogenesis-specific cytokine production in
human pulmonary endothelial cells, HPMEC-ST1.6R infected with dengue-2 and dengue
3 virus.
AB - In this study, the ability of dengue virus serotypes 2 (DENV-2) and 3 (DENV-3) to
infect and induce increased production of proinflammatory cytokines in a
pulmonary endothelial cell line (HPMEC-ST1.6R) was investigated. This cell line
exhibits the major constitutive and inducible endothelial cell characteristics,
as well as angiogenic response. DENV-2 and DENV-3 infection was confirmed by an
observed cytopathic effect (CPE), as well as RT-PCR and immunofluorescence
assays. Increases in Th-1 and Th-2 cytokines IL-4, IL-8, IL-6, IL-10, GM-CSF, INF
gamma, and tumor necrosis factor (TNF-alpha) within DENV-2- and DENV-3-infected
cells were demonstrated using a microbead-based Bio-plex assay. Proinflammatory
cytokine increases and the expression of a potent angiogenic inducer protein,
VEGF were confirmed by dot-blot analysis using the TranSignal Human Angiogenesis
Antibody Array. Dengue virus-infected HPMEC-ST1.6R cells exhibited an elongated
cytoplasmic morphology, possibly representing a response to VEGF and activation
of angiogenesis. The increased levels of Th-1 cytokines and VEGF in DENV-2 virus
infected-HPMEC-ST1.6R could be distinguished from those infected by DENV-3. This
suggests that cytokine patterns associated with DENV infections may be serotype
and strain-specific. The experimental approaches described here could be
developed further into a useful diagnostic tool for the characterization of
dengue hemorrhagic fever cases, leading to enhancement of treatment therapy.
PMID- 17034873
TI - Controlling hippocampal output: the central role of subiculum in hippocampal
information processing.
AB - The subiculum has a central position between the hippocampus proper and
entorhinal and other cortices, as well as a range of subcortical structures. The
functional role of subiculum within the hippocampal formation circuit remains
largely unexplored and a theoretical and experimental consensus on its functions
has yet to emerge. Presented here is a simple and speculative model of the
functions of the subiculum, based partly on anatomical, behavioural and
neurophysiological considerations. The model suggests, firstly, that the
subiculum acts to amplify hippocampal output, given the prominent bursting
behaviour of its neurons and, secondly, that there is a dorso-ventral segregation
of function within the subiculum. The dorsal component appears principally
concerned with the processing of information about space, movement and memory,
whereas the ventral component appears to play a major regulatory role in the
inhibition of the HPA axis.
PMID- 17034874
TI - Response acquisition with delayed reinforcement in a rodent model of attention
deficit/hyperactivity disorder (ADHD).
AB - The spontaneously hypertensive rat (SHR) has been shown to exhibit behavioral
characteristics analogous to those exhibited by humans diagnosed with attention
deficit/hyperactivity disorder (ADHD). The present study was conducted to further
evaluate the validity of the SHR model of ADHD by characterizing learning of a
novel response under conditions of delayed reinforcement. Seven experimentally
naive SHRs and a control group of seven normotensive Wistar-Kyoto (WKY) rats were
exposed to a contingency where one lever press initiated pellet delivery after a
15-s, resetting delay. Rats in both groups acquired lever pressing, and the
pattern of acquisition was well described with a three-parameter, sigmoidal
equation. Response acquisition was retarded in the SHRs; they took longer to
acquire the behavior, exhibited lower response rates and earned fewer reinforcers
over the course of the experiment. When reinforcer delivery was made immediate in
a subsequent condition, the SHRs exhibited higher response rates than the WKY,
suggesting that the lower rates of responding seen in the SHRs were due to the
reinforcer delay. The results replicate previous research on response acquisition
with delayed reinforcement and provide further validation of the SHR strain as a
model of ADHD. Like humans diagnosed with ADHD, the SHRs appear to be
hypersensitive to delayed consequences, which in the present context, interfered
with learning a novel behavior.
PMID- 17034876
TI - Characterization of the rabbit HKalpha2 gene promoter.
AB - The HKalpha2 gene directs synthesis of the HKalpha2 subunit of the H(+), K(+)
ATPase. In the kidney and colon, the gene is highly expressed and is thought to
play a role in potassium (K(+)) conservation. The rabbit has been an important
experimental system for physiological studies of ion transport in the kidney, so
the rabbit HKalpha2 gene has been cloned and characterized. The genomic clones
and the previously reported HKalpha2a and HKalpha2c subunit cDNAs provided a
means to address several issues regarding the structure and expression of the
HKalpha2 gene. First, the genomic organization established that the rabbit
HKalpha2 gene was unambiguously homologous to the mouse HKalpha2 gene and the
human ATP1AL1 gene. Second, the mapping of the transcription start site for the
alternate transcript, HKalpha2c, confirmed that it was an authentic rabbit
transcript. Finally, isolation of DNA from the 5' end of the HKalpha2 gene
enabled us to initiate studies on its regulation in the rabbit cortical
collecting duct. The promoter and two putative negative regulatory regions were
identified and the effect of cell confluency on gene expression was studied.
PMID- 17034877
TI - Peroxisomes and oxidative stress.
AB - The discovery of the colocalization of catalase with H2O2-generating oxidases in
peroxisomes was the first indication of their involvement in the metabolism of
oxygen metabolites. In past decades it has been revealed that peroxisomes
participate not only in the generation of reactive oxygen species (ROS) with
grave consequences for cell fate such as malignant degeneration but also in cell
rescue from the damaging effects of such radicals. In this review the role of
peroxisomes in a variety of physiological and pathological processes involving
ROS mainly in animal cells is presented. At the outset the enzymes generating and
scavenging H2O2 and other oxygen metabolites are reviewed. The exposure of
cultured cells to UV light and different oxidizing agents induces peroxisome
proliferation with formation of tubular peroxisomes and apparent upregulation of
PEX genes. Significant reduction of peroxisomal volume density and several of
their enzymes is observed in inflammatory processes such as infections, ischemia
reperfusion injury and hepatic allograft rejection. The latter response is
related to the suppressive effects of TNFalpha on peroxisomal function and on
PPARalpha. Their massive proliferation induced by a variety of xenobiotics and
the subsequent tumor formation in rodents is evidently due to an imbalance in the
formation and scavenging of ROS, and is mediated by PPARalpha. In PEX5-/- mice
with the absence of functional peroxisomes severe abnormalities of mitochondria
in different organs are observed which resemble closely those in respiratory
chain disorders associated with oxidative stress. Interestingly, no evidence of
oxidative damage to proteins or lipids, nor of increased peroxide production has
been found in that mouse model. In this respect the role of PPARalpha, which is
highly activated in those mice, in prevention of oxidative stress deserves
further investigation.
PMID- 17034875
TI - Modeling early cortical serotonergic deficits in autism.
AB - Autism is a developmental brain disorder characterized by deficits in social
interaction, language and behavior. Brain imaging studies demonstrate increased
cerebral cortical volumes and micro- and macro-scopic neuroanatomic changes in
children with this disorder. Alterations in forebrain serotonergic function may
underlie the neuroanatomic and behavioral features of autism. Serotonin is
involved in neuronal growth and plasticity and these actions are likely mediated
via serotonergic and glutamatergic receptors. Few animal models of autism have
been described that replicate both etiology and pathophysiology. We report here
on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice
that mimics neurochemical and structural changes in cortex and, in addition,
displays a behavioral phenotype consistent with autism. Newborn male and female
mice were depleted of forebrain 5-HT with injections of the serotonergic
neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial
forebrain bundle (mfb). Behavioral testing of these animals as adults revealed
alterations in social, sensory and stereotypic behaviors. Lesioned mice showed
significantly increased cortical width. Serotonin immunocytochemistry showed a
dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex
until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT
transporters was significantly but transiently reduced in cerebral cortex of 5,7
DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We
hypothesize that increased cerebral cortical volume and sensorimotor, cognitive
and social deficits observed in both 5-HT-depleted animals and in individuals
with autism, may be the result of deficiencies in timely axonal pruning to key
cerebral cortical areas.
PMID- 17034878
TI - Peroxisomes and bile acid biosynthesis.
AB - Peroxisomes play an important role in the biosynthesis of bile acids because a
peroxisomal beta-oxidation step is required for the formation of the mature C24
bile acids from C27-bile acid intermediates. In addition, de novo synthesized
bile acids are conjugated within the peroxisome. In this review, we describe the
current state of knowledge about all aspects of peroxisomal function in bile acid
biosynthesis in health and disease. The peroxisomal enzymes involved in the
synthesis of bile acids have been identified, and the metabolic and pathologic
consequences of a deficiency of one of these enzymes are discussed, including the
potential role of nuclear receptors therein.
PMID- 17034879
TI - Voltage-gated calcium channels in genetic diseases.
AB - Voltage-gated calcium channels (VGCCs) mediate calcium entry into excitable cells
in response to membrane depolarization. During the past decade, our understanding
of the gating and functions of VGCCs has been illuminated by the analysis of
mutations linked to a heterogeneous group of genetic diseases called "calcium
channelopathies". Calcium channelopathies include muscular, neurological, cardiac
and vision syndromes. Recent data suggest that calcium channelopathies result not
only from electrophysiological defects but also from altered alpha(1)/Ca(V)
subunit protein processing, including folding, posttranslational modifications,
quality control and trafficking abnormalities. Overall, functional analyses of
VGCC mutations provide a more comprehensive view of the corresponding human
disorders and offer important new insights into VGCC function. Ultimately, the
understanding of these pathogenic channel mutations should lead to improved
treatments of such hereditary diseases in humans.
PMID- 17034880
TI - Exocytosis in neuroendocrine cells: new tasks for actin.
AB - Most secretory cells undergoing calcium-regulated exocytosis in response to cell
surface receptor stimulation display a dense subplasmalemmal actin network, which
is remodeled during the exocytotic process. This review summarizes new insights
into the role of the cortical actin cytoskeleton in exocytosis. Many earlier
findings support the actin-physical-barrier model whereby transient
depolymerization of cortical actin filaments permits vesicles to gain access to
their appropriate docking and fusion sites at the plasma membrane. On the other
hand, data from our laboratory and others now indicate that actin polymerization
also plays a positive role in the exocytotic process. Here, we discuss the
potential functions attributed to the actin cytoskeleton at each major step of
the exocytotic process, including recruitment, docking and fusion of secretory
granules with the plasma membrane. Moreover, we present actin-binding proteins,
which are likely to link actin organization to calcium signals along the
exocytotic pathway. The results cited in this review are derived primarily from
investigations of the adrenal medullary chromaffin cell, a cell model that is
since many years a source of information concerning the molecular machinery
underlying exocytosis.
PMID- 17034881
TI - Cysteine-string protein isoform beta (Cspbeta) is targeted to the trans-Golgi
network as a non-palmitoylated CSP in clonal beta-cells.
AB - Cysteine string proteins (CSPs) belong to the DnaJ-like chaperone family and play
an important role in regulated exocytosis in neurons and endocrine cells. The
palmitoylation of several residues in a cysteine string domain may anchor CSPs to
the exocytotic vesicle surface and in pancreatic beta-cells, Cspalpha is
localized on insulin containing large dense core vesicles (LDCVs). An isoform
closely related to Cspalpha, Cspbeta, has been obtained from testis cell cDNA
libraries. To gain insights on this isoform and more generally on the properties
of CSPs, we compared Cspalpha and Cspbeta. In pull-down experiments, Cspbeta was
able to interact to the same extent with two of the known Cspalpha chaperone
partners, Hsc70 and SGT. Upon transient overexpression in clonal beta-cells,
Cspbeta but not Cspalpha was mainly produced as a non-palmitoylated protein and
mutational analysis indicated that domains distinct from the cysteine string are
responsible for this difference. As Cspbeta remained tightly bound to membranes,
intrinsic properties of CSPs are sufficient for interactions with membranes.
Indeed, recombinant Cspalpha and Cspbeta were capable to interact with membranes
even in their non-palmitoylated forms. Furthermore, overexpressed Cspbeta was not
associated with LDCVs, but was localized at the trans-Golgi network. Our results
suggest a possible correlation between the specific membrane targeting and the
palmitoylation level of CSPs.
PMID- 17034882
TI - Emerging perspectives in store-operated Ca2+ entry: roles of Orai, Stim and TRP.
AB - Depletion of intracellular Ca2+ stores induces Ca2+ influx across the plasma
membrane through store-operated channels (SOCs). This store-operated Ca2+ influx
is important for the replenishment of the Ca2+ stores, and is also involved in
many signaling processes by virtue of the ability of intracellular Ca2+ to act as
a second messenger. For many years, the molecular identities of particular SOCs,
as well as the signaling mechanisms by which these channels are activated, have
been elusive. Recently, however, the mammalian proteins STIM1 and Orai1 were
shown to be necessary for the activation of store-operated Ca2+ entry in a
variety of mammalian cells. Here we present molecular, pharmacological, and
electrophysiological properties of SOCs, with particular focus on the roles that
STIM1 and Orai1 may play in the signaling processes that regulate various
pathways of store-operated entry.
PMID- 17034883
TI - Left ventricular noncompaction and mid-caviter narrowing associated with
Ebstein's anomaly: three-dimensional transthoracic echocardiographic image.
AB - An 50 year-old asymptomatic female was admitted to preoperative cardiovascular
evaluation for noncardiac surgery. Two-dimensional transthoracic echocardiography
demonstrated that left ventricular dimensions and ejection fraction were normal.
The mitral valve was normal both in morphology and function. The attached margin
of septal and anterior leaflet of the tricuspid valve was apically displaced. But
right ventricle and right atrium dimensions were normal, and Doppler
interrogation showed a slight tricuspid regurgitation. Two and three-dimensional
transthoracic echocardiography showed prominent numerous trabeculations in the
left ventricular apex. Colour flow Doppler studies confirmed the presence of
blood flow within the trabeculations. Multi-plane three-dimensional transthoracic
echocardiography showed a muscular band leading to left ventricular mid-caviter
narrowing. Pulse wave Doppler echocardiography demonstrated that no
intraventricular gradient existed. Ventricular noncompaction associated with
Ebstein's malformation has been reported. But left ventricular noncompaction and
mid-caviter narrowing associated with Ebstein's anomaly have not been reported so
far.
PMID- 17034884
TI - Effects of oxytocin on cardiomyocyte differentiation from mouse embryonic stem
cells.
AB - This study sought to investigate the presence of oxytocin receptors and the
possible biological role of oxytocin as an effective factor in the
differentiation of embryonic stem cells (ESCs) into cardiomyocytes. Mouse ESCs
were cultivated in hanging drops to form embryoid bodies (EBs). The EBs were then
treated with and without oxytocin (experimental and control groups). Up to 30
days after plating, contraction and beating frequency were monitored and
evaluated daily. The growth characteristics of the ESC-derived cardiomyocytes
were assessed by cardioactive drugs, immunocytochemistry, transmission electron
microscopy (TEM) and reverse transcription-polymerase chain reaction (RT-PCR). In
the experimental group, the percentage of the EBs with spontaneous contraction
was significantly increased from 17th day onward. The spontaneous beating
frequency of each EB in both groups was also changed with cardioactive drugs such
as Bay K, carbachol, isopernaline and phenylephrine. However, in the experimental
group, changes with isopernaline were more pronounced at the early and
intermediate stages of cardiomyocyte development. The beating cells of both
groups, stained positive with anti alpha-actinin, desmin, cardiac troponin I and
connexin antibodies, and revealed similar ultrastructural features. Oxytocin
receptors were detected on the ESCs and derived-differentiated cells. In
addition, cardiac-specific genes such as cardiac alpha- and beta-myosin heavy
chain, myosin light chain-2v, and atrial natriuretic factor were also detected in
the ESC-derived differentiated cells of both groups. In the experimental group,
all the specific genes, with the exception of alpha-myosin heavy chain, were more
pronounced at the early stage of cardiomyocyte development. In conclusion,
oxytocin has receptors on undifferentiated ESCs and derived differentiated cells,
and in spite of better improvement of the EBs with spontaneous contraction, it
can only promote the early maturation of ESC-derived cardiomyocytes in terms of
chronotropic responses and expression of cardiac-specific genes, and have no
effect on ultrastructural characteristics of cardiomyocytes in any stage of
development.
PMID- 17034885
TI - The impact of inflammation on the development, successful cardioversion,
recurrence and/or perpetuation of atrial fibrillation.
PMID- 17034886
TI - Subclinical carditis in rheumatic fever: a systematic review.
AB - OBJECTIVE: Subclinical carditis (SCC)--pathological valvular regurgitation
detected on echocardiography that is not evident clinically--has been reported in
acute rheumatic fever (ARF), but its significance is unknown. We aimed to review
the existing literature on the prevalence and outcome of SCC in ARF. METHODS: We
conducted a systematic literature review using MEDLINE. RESULTS: Prevalences of
SCC in ARF ranged from 0% (in one study only) to 53% in 23 articles. The weighted
pooled prevalence of SCC in ARF was 16.8% (95%CI 11.9 to 21.6). This increased
slightly to 18.1% (95%CI 11.1 to 25.2) by analysing only the 10 studies that
applied full World Health Organization criteria for SCC diagnosis. The weighted
pooled prevalence of persistence or deterioration of SCC 3 to 23 months after ARF
diagnosis was 44.7% (95%CI 19.3 to 70.2) from 11 articles. CONCLUSION: SCC is
relatively common in ARF. Although some studies suggest that SCC lesions may
persist or deteriorate, the available data are insufficient and of poor quality,
so no confident conclusions can be drawn about the prognosis of SCC. Until better
studies are conducted, clinicians will have to make management decisions that are
not evidence-based. These decisions will have important practical implications
for the use of echocardiography acutely and during follow-up, diagnosis of ARF,
and duration of secondary prophylaxis in patients with SCC.
PMID- 17034887
TI - Management of feral domestic cats in the urban environment of Rome (Italy).
AB - In Italy, which is rabies-free, the national Law No. 281 [Legge Nazionale 14
agosto 1991. No. 281: Legge Quadro in materia di animali di affezione e
prevenzione del randagismo. Gazz. Uff. Rep. Ital. no 203 del 30 agosto 1991: p.
3] on the management of pets and on the control of feral cats has introduced the
no-kill policy for this species. Thus, "trap-neuter-release" (TNR) programs have
been carried out for >10 years. In this paper we present data on registered
colonies and censused cats in Rome from 1991 to 2000; the results of the
neutering campaign from 1991 to 2000; and a survey, on 103 cat colonies, on the
effects of demographic control of urban feral-cat colonies in the city of Rome,
carried out by the local Veterinary Public Services (VPS) in collaboration with
the associations of cat care-takers. In 10 years almost 8000 were neutered and
reintroduced in their original colony. The spay/neuter campaigns brought about a
general decrease in cat number but the percentage of cat immigration (due to
abandonment and spontaneous arrival) is around 21%. This suggests that all these
efforts without an effective education of people to control the reproduction of
house cats (as a prevention for abandonment) are a waste of money, time and
energy.
PMID- 17034888
TI - Medicare balance billing restrictions: impacts on physicians and beneficiaries.
AB - Beginning in the late 1980s, states and the federal government restricted the
ability of physicians to "balance bill" Medicare beneficiaries for charges in
excess of the copayment and reimbursement amounts approved by Medicare. In this
paper, I provide empirical evidence that this policy change resulted in a 9%
reduction in out-of-pocket medical expenditures by elderly households. In spite
of the change in marginal reimbursement to physicians, however, I find little
evidence that the restrictions affected patterns of care. Thus, this restriction
on the prices charged by physicians amounted to a transfer from affected
physicians to affected patients.
PMID- 17034889
TI - Use of a real time PCR assay for detection of the ctxA gene of Vibrio cholerae in
an environmental survey of Mobile Bay.
AB - Toxigenic Vibrio cholerae, the etiological agent of cholera, is a natural
inhabitant of the marine environment and causes severe diarrheal disease
affecting thousands of people each year in developing countries. It is the
subject of extensive testing of shrimp produced and exported from these
countries. We report the development of a real time PCR (qPCR) assay to detect
the gene encoding cholera toxin, ctxA, found in toxigenic V. cholerae strains.
This assay was tested against DNA isolated from soil samples collected from
diverse locations in the US, a panel of eukaryotic DNA from various sources, and
prokaryotic DNA from closely related and unrelated bacterial sources. Only Vibrio
strains known to contain ctxA generated a fluorescent signal with the 5' nuclease
probe targeting the ctxA gene, thus confirming the specificity of the assay. In
addition, the assay was quantitative in pure culture across a six-log dynamic
range down to <10 CFU per reaction. To test the robustness of this assay,
oysters, aquatic sediments, and seawaters from Mobile Bay, AL, were analyzed by
qPCR and traditional culture methods. The assay was applied to overnight alkaline
peptone water enrichments of these matrices after boiling the enrichments for 10
min. Toxigenic V. cholerae strains were not detected by either qPCR or
conventional methods in the 16 environmental samples examined. A novel exogenous
internal amplification control developed by us to prevent false negatives
identified the samples that were inhibitory to the PCR. This assay, with the
incorporated internal control, provides a highly specific, sensitive, and rapid
detection method for the detection of toxigenic strains of V. cholerae.
PMID- 17034890
TI - Ethical considerations of neuroscience research: the perspectives on neuroethics
in Japan.
AB - Recent technologies and developments in neuroscience have contributed to
remarkable scientific discoveries, and have also raised many new philosophical,
ethical, legal, and social issues. Research in "neuroethics" has identified
various ethical issues, which will be difficult for current biomedical ethics to
resolve from both an experimental and a social perspective, such as criminal
applications of brain scans, incidental findings during non-clinical brain
imaging, and cognitive enhancement. Although American and European neuroscience
societies have demonstrated immediate, concrete reactions to these ethical
issues, including academic conferences, study programs, and publications,
Japanese neuroscientists have so far produced little response. Ethics is tightly
linked with one's religion, nationality, culture, and social background, whereas
science is tightly linked with the demand, economics, and politics of the society
to which individuals belong. Taken together, it is important and necessary for
Japanese neuroscientists to consider the ethical problems in Japanese
neuroscience. In this paper, we first review the history of neuroethics in the
world, and then report the less-developed ethical issues in the Japanese
neuroscience community, focusing on neuroimaging and manipulative neuroscience as
a first step in discussing how to apply principles in neuroethics to this rapidly
progressing field of research.
PMID- 17034891
TI - Cervical cancer treatment with a locally insertable controlled release delivery
system.
AB - Local delivery of cancer chemotherapeutics enables sustained drug levels at the
site of action thereby reducing systemic side effects. A novel insertable
polymeric drug delivery system for cervical cancer treatment is presented.
Cisplatin, the first line of therapy employed for cervical cancers, was
incorporated in a poly(ethylene-co-vinyl acetate) (EVAc) device that is similar
to those currently used for vaginal contraceptive delivery. Cisplatin crystals
were uniformly dispersed in the polymeric system without undergoing significant
dissolution in the polymer matrix. Cisplatin dissolution from the devices was
biphasic, consistent with a matrix-type controlled-release system with an initial
rapid release phase followed by a slower, near linear release phase. Depending on
the drug loading in the polymeric devices, the near-linear release phase varied
in rate according to both empirical, linear curve-fitting (0.38+/-0.15 microg/day
to 46.9+/-10.0 microg/day) and mechanistic, diffusion analysis based upon
diffusion through a porous structure (D(app) from 1.3+/-0.5 x 10(-9) cm2/s to
5.8+/-0.3 x 10(-12) cm2/s). The devices were tested for in vitro activity and
found to be effective against both HPV positive and HPV negative cervical cancer
cell lines. Preliminary studies indicate that this delivery system would be a
good candidate for investigation as a choice of treatment in cervical cancers.
PMID- 17034892
TI - Silk sericin-insulin bioconjugates: synthesis, characterization and biological
activity.
AB - When silk fiber derived from Bombyx mori was subjected to degumming treatments
twice in water and subsequent degraded processing in slightly alkaline aqueous
solution under high-temperature and high-pressure, the water-soluble silk sericin
peptides (SS) with different molecular mass from 10 to 70 kDa were obtained. The
sericin peptides could be conjugated covalently with insulin alone with cross
linking reagent glutaraldehyde. The physicochemical properties of the silk
sericin-insulin (SS-Ins) conjugates were determined by Enzyme-Linked
Immunosorbent Assay (ELISA). The biological activities of SS-Ins bioconjugates
were investigated in vitro and in vivo. The results in human serum in vitro
indicated that the half-life of the synthesized SS-Ins derivatives was 2.3 and
2.7 times more than that of bovine serum albumin-insulin (BSA-Ins) conjugates and
intact insulin, respectively. The pharmacological activity of SS-Ins
bioconjugates lengthened to 21 h in mice in vivo, which was over 4 times longer
than that of the native insulin. The immunogenicity of silk sericin and the
antigenicity of SS-Ins derivatives were not observed in both rabbits and mice.
The bioconjugation of insulin with silk sericin protein evidently improved both
physicochemical and biological stability of the polypeptide.
PMID- 17034893
TI - Carotid atherosclerosis associated to metabolic syndrome but not BMI in healthy
menopausal women.
AB - BACKGROUND: Obesity and the metabolic syndrome (MS) frequently coexist. Both are
apparently associated to cardiovascular disease. However, the contribution of
obesity to cardiovascular risk, independent of the presence of the metabolic
syndrome, remains controversial. The purpose of this study was to investigate
whether the subclinical carotid atherosclerosis prevalence is different in obese
postmenopausal women with and without the metabolic syndrome. METHODS: On the
basis of consecutive recruitment, 313 postmenopausal women underwent a clinical,
biochemical and ultrasound characterization. Women affected by cardiovascular
disease or diabetes were excluded from the study. RESULTS: Among enrolled women
the metabolic syndrome and body mass index (BMI) resulted strongly associated,
but only metabolic syndrome was associated with carotid atherosclerosis, a well
known marker of cardiovascular disease. Similarly, increases in BMI unit (normal
to overweight to obese) were not associated with carotid atherosclerosis whereas
metabolic status (normal to metabolic syndrome) conferred an approximate three
fold adjusted odds of carotid atherosclerosis. CONCLUSIONS: The metabolic
syndrome but not obesity is associated to carotid atherosclerosis in
postmenopausal women. Although it remains prudent to recommend weight loss in
overweight and obese women, evaluation and control of metabolic risk factors
should be considered the main goal to prevent cardiovascular and cerebrovascular
disease.
PMID- 17034894
TI - Work stress and low emotional support is associated with increased risk of future
type 2 diabetes in women.
AB - A case-referent study nested within a population-based health survey investigated
the associations between psychosocial stress, such as work stress and low
emotional support, and future development of type 2 diabetes among occupationally
working middle-aged men and women. All participants in a health survey conducted
during 1989-2000 (n=33,336) in Umea in northern Sweden, were included. We
identified 191 cases, who were not diabetic initially but were diagnosed with
type 2 diabetes after 5.4+/-2.6 years. Two age- and sex-matched referents were
selected for each case. Multivariate logistic regression analyses and interaction
effects between variables were evaluated. In women, passive or tense working
situations were associated with future type 2 diabetes with odds ratios 3.6 (95%
confidence interval 1.1-11.7) and 3.6 (1.0-13.3), respectively, and also low
emotional support 3.0 (1.3-7.0). These associations were not seen in men. In
women, they remained after adjustment for BMI, civil status and educational
level, and there were also tendencies for interactions between work stress and
low emotional support. In conclusion, work stress and low emotional support may
increase the risk of type 2 diabetes in women, but not in men. These findings
contribute to our understanding of psychosocial stress as potential risk factors
for type 2 diabetes in a Swedish population.
PMID- 17034895
TI - Hepatitis A virus infection suppresses hepatitis C virus replication and may lead
to clearance of HCV.
AB - BACKGROUND/AIMS: The significance of hepatitis A virus (HAV) super-infection in
patients with chronic hepatitis C had been a matter of debate. While some studies
suggested an incidence of fulminant hepatitis A of up to 35%, this could not be
confirmed by others. METHODS: We identified 17 anti-HCV-positive patients with
acute hepatitis A from a cohort of 3170 anti-HCV-positive patients recruited at a
single center over a period of 12 years. RESULTS: Importantly, none of the anti
HCV-positive patients had a fulminant course of hepatitis A. HCV-RNA was detected
by PCR in 84% of the anti-HCV-positive/anti-HAV-IgM-negative patients but only in
65% of anti-HCV-positive patients with acute hepatitis A (p=0.03), indicating
suppression of HCV replication during hepatitis A. Previous HAV infection had no
effect on HCV replication. After recovery from hepatitis A, an increased HCV
replication could be demonstrated for 6 out of 9 patients with serial
quantitative HCV-RNA values available while 2 patients remained HCV-RNA negative
after clearance of HAV throughout follow-up of at least 2 years. CONCLUSIONS: HAV
super-infection is associated with decreased HCV-RNA replication which may lead
to recovery from HCV in some individuals. Fulminant hepatitis A is not frequent
in patients with chronic hepatitis C recruited at a tertiary referral center.
PMID- 17034896
TI - Genetic mutation in hepatic adenoma: seeing is believing.
PMID- 17034897
TI - Juvenile hemochromatosis.
PMID- 17034898
TI - Priority setting at the micro-, meso- and macro-levels in Canada, Norway and
Uganda.
AB - The objectives of this study were (1) to describe the process of healthcare
priority setting in Ontario-Canada, Norway and Uganda at the three levels of
decision-making; (2) to evaluate the description using the framework for fair
priority setting, accountability for reasonableness; so as to identify lessons of
good practices. METHODS: We carried out case studies involving key informant
interviews, with 184 health practitioners and health planners from the macro
level, meso-level and micro-level from Canada-Ontario, Norway and Uganda
(selected by virtue of their varying experiences in priority setting). Interviews
were audio-recorded, transcribed and analyzed using a modified thematic approach.
The descriptions were evaluated against the four conditions of "accountability
for reasonableness", relevance, publicity, revisions and enforcement. Areas of
adherence to these conditions were identified as lessons of good practices; areas
of non-adherence were identified as opportunities for improvement. RESULTS: (i)
DESCRIPTION: at the macro-level, in all three countries, cabinet makes most of
the macro-level resource allocation decisions and they are influenced by
politics, public pressure, and advocacy. Decisions within the ministries of
health are based on objective formulae and evidence. International priorities
influenced decisions in Uganda. Some priority-setting reasons are publicized
through circulars, printed documents and the Internet in Canada and Norway. At
the meso-level, hospital priority-setting decisions were made by the hospital
managers and were based on national priorities, guidelines, and evidence.
Hospital departments that handle emergencies, such as surgery, were prioritized.
Some of the reasons are available on the hospital intranet or presented at
meetings. Micro-level practitioners considered medical and social worth criteria.
These reasons are not publicized. Many practitioners lacked knowledge of the
macro- and meso-level priority-setting processes. (ii) Evaluation-relevance:
medical evidence and economic criteria were thought to be relevant, but lobbying
was thought to be irrelevant. Publicity: all cases lacked clear and effective
mechanisms for publicity. REVISIONS: formal mechanisms, following the planning
hierarchy, were considered less effective, informal political mechanisms were
considered more effective. Canada and Norway had patients' relations officers to
deal with patients' dissensions; however, revisions were more difficult in
Uganda. Enforcement: leadership for ensuring decision-making fairness was not
apparent. CONCLUSIONS: The different levels of priority setting in the three
countries fulfilled varying conditions of accountability for reasonableness, none
satisfied all the four conditions. To improve, decision makers at the three
levels in all three cases should engage frontline practitioners, develop more
effectively publicized reasons, and develop formal mechanisms for challenging and
revising decisions.
PMID- 17034899
TI - Functionality of unspliced XBP1 is required to explain evolution of overlapping
reading frames.
AB - Eukaryotic genes with overlapping reading frames exemplify some of the most
striking biological phenomena. Transcript of one such gene, the gene encoding X
box protein (XBP1), has evolved a mechanism for "on-demand" switching of
translation between two overlapping reading frames. Despite the existence of this
elaborate system, only one reading frame was believed to be functional. Here, we
show that XBP1 evolves in a fashion that is only consistent with functionality of
both reading frames. Our study provides a novel evolutionary framework for the
analysis of loci with overlapping reading frames, which can be used for
identification and analyses of novel dual-coding genes.
PMID- 17034900
TI - From Mendelian to molecular genetics: the Xiphophorus melanoma model.
AB - In human tumor biopsies it is almost impossible to pinpoint the particular
molecular abnormalities that determine neoplasia. In animal models where
tumorigenesis is initiated by clearly defined genetic events, it is possible to
study the genes and their functions that make a normal cell become a fully
malignant cancer cell. In the fish Xiphophorus, melanoma can be initiated by
simple crossings, and the signaling pathways that govern tumor growth and
progression can be delineated. This model offers the prospect of obtaining a
complete picture of the molecular changes and regulatory networks underlying
tumor formation, which should contribute to a better understanding of some
general principles of cancer biology, and identify new targets for melanoma
research in particular.
PMID- 17034901
TI - Polymorphisms in the DNA repair genes XRCC1, APEX1, XRCC3 and NBS1, and the risk
for lung cancer in never- and ever-smokers.
AB - This case-control study examines the association between lung cancer and genetic
polymorphisms in two base excision repair (BER) genes, XRCC1 and APEX1 and two
genes involved in homologous recombination repair (HR), XRCC3 and NBS1. Never
smoking lung cancer patients were recruited, and also the next diagnosed ever
smoking case of the same gender and age group. Controls were recruited from the
regional population register, frequency matched to cases by hospital catchment
area, gender, age group and smoking category. As a result more than 70% of the
study population were women. A total of 331 individuals were analysed. Presence
of the XRCC1 399Gln allele was associated with a significantly decreased risk for
lung cancer among non-smoking women (odds ratio (OR) 0.4, 95% confidence interval
(CI) 0.2-0.9). No significant effect was seen with the APEX1 polymorphism. Women
smokers carrying the XRCC3 241Met allele showed a significantly decreased risk
for lung cancer (OR 0.3, CI 0.2-0.7). The NBS1 185Gln allele was significantly
associated with an increased risk for lung cancer among non-smoking women (OR
2.2, CI 1.0-4.8) and low-dose smoking women (OR 4.8, CI 1.5-15.7). The protective
effect of the variant XRCC3 241Met allele was strengthened when combined with the
low-risk Glu185 allele of the NBS1 gene. Smokers (OR 0.38, CI 0.16-0.90) and
women (OR 0.42, CI 0.21-0.85) with at least three low-risk alleles in these two
HR genes showed a significantly decreased risk for lung cancer. Thus, in spite of
a relatively small study population, this study, including a comparatively large
number of never-smokers and women, presents several novel aspects on genetic
susceptibility to lung cancer. Our results show that the genetic variation in
XRCC1, XRCC3 and NBS1 influence lung cancer susceptibility among women, and that
combinations of risk alleles in the two HR genes can enhance the effects.
PMID- 17034902
TI - Motivational state modulates the hedonic value of food images differently in men
and women.
AB - We investigated visual alimentary alliesthesia in non-fasted (N = 369) and fasted
participants (N = 257) viewing photographs of food. Fasted participants were
asked to not eat for 12 h before the session. Each participant was shown food and
non-food images and rated each image on valence (i.e., pleasantness). The
strongest evidence of alliesthesia was found in women. Fasting enhanced the
pleasantness of food images for each of the food categories in women, although
this alliesthesia effect was smaller in response to dessert foods compared to the
less-pleasantly-rated food categories. In addition, non-fasting women exhibited
significant positive correlations between hunger ratings and valence ratings of
three of the five food categories. There was no significant difference in valence
ratings of food between fasting vs. non-fasting men, but non-fasting men showed
correlations between hunger and valence that were similar to those observed among
the women. No evidence was found of hunger- or fasting-induced enhancement of
hedonic ratings of non-foods in women or men, indicating the specificity of the
alliesthesia effect for the food images only.
PMID- 17034903
TI - Attitudes towards disability in an undergraduate nursing curriculum: the effects
of a curriculum change.
AB - Through improved technology and treatment and ongoing de-institutionalisation,
nurses will encounter growing numbers of people with disabilities in the New
Zealand community and hospitals. Quality of nursing care is influenced by
attitude and this study was to evaluate the effect of a curriculum change on the
attitudes of two different streams of student nurses towards people with
disabilities. During the year 2002 a focused disability unit was introduced to
the revised undergraduate nursing curriculum of a major educational institution
in New Zealand. The opportunity arose to consider student nurses' attitudes
toward disabled people, comparing two streams of students undertaking two
different curricula. A convenience sample of students completed the attitudes
toward disabled persons questionnaire form B (Yuker, H.E., Block, J.R., Younng,
J.H., 1970. The Measurement of Attitudes Toward Disabled Persons. INA Mend
Institute, New York), prior to and on completion of their relevant disability
unit. No statistically significant difference in scores was demonstrated. A
number of possible reasons for this are suggested.
PMID- 17034904
TI - Nursing students' mathematic calculation skills.
AB - This mixed method study used a pre-test/post-test design to evaluate the efficacy
of a teaching strategy in improving beginning nursing student learning outcomes.
During a 4-week student teaching period, a convenience sample of 54 sophomore
level nursing students were required to complete calculation assignments, taught
one calculation method, and mandated to attend medication calculation classes.
These students completed pre- and post-math tests and a major medication
mathematic exam. Scores from the intervention student group were compared to
those achieved by the previous sophomore class. Results demonstrated a
statistically significant improvement from pre- to post-test and the students who
received the intervention had statistically significantly higher scores on the
major medication calculation exam than did the students in the control group. The
evaluation completed by the intervention group showed that the students were
satisfied with the method and outcome.
PMID- 17034905
TI - Energy requirements in frail elderly people: a review of the literature.
AB - This review collates studies of healthy, sick, underweight (BMI < or = 21 kg/m2)
and very elderly people (> or = 90 yr), in whom resting energy expenditure (REE)
was measured using indirect calorimetry. We have observed the following: (1) REE,
when adjusted for differences in both body weight and fat-free mass (FFM), is
similar in healthy and in sick elderly people being 20 and 28 kcal/kg of FFM per
day, respectively, (2) their nutritional status influences their energy
requirements given that weight-adjusted REE increases in line with a decrease in
BMI, (3) total energy expenditure is lower in sick elderly people given that
their physical activity level, i.e. the ratio of total energy expenditure to REE,
is reduced during disease averaging at 1.36, (4) energy intake (EI) being only
1.23 x REE is insufficient to cover energy requirements in sick elderly patients,
whereas the EI of healthy elderly people appears sufficient to cover
requirements, and finally, (5) gender ceases to be a determinant of REE in people
aged 60 yr or over, with the Harris & Benedict equation capable of accurately
predicting mean REE in this population, whether healthy or sick.
PMID- 17034906
TI - Increased risk of chronic suppurative lung disease after measles or pertussis in
non-vaccinated children.
AB - We retrospectively analysed 23 children originating from Campania--Southern Italy
-with recurrent pneumonia and chest high-resolution computed tomography (HRCT)
proven bronchiectasis. In six patients (26%) who had not undergone measles or
pertussis vaccination, recurrent pneumonia started after an episode of lower
respiratory tract infection complicating pertussis (n=2) or measles (n=4),
contracted at a mean age of 3.6 years. Thirty-three percent (2/6) and 67% (4/6)
of the patients had bilateral or monolobar disease, respectively, while in two
subjects (33%) bronchiectasis were found in all lobes. These findings indicate an
increased risk of developing bronchiectasis after measles or pertussis.
PMID- 17034907
TI - Validation of a routine opsonophagocytosis assay to predict invasive pneumococcal
disease efficacy of conjugate vaccine in children.
AB - Immunological evaluation of the clinical impact of vaccines designed to protect
against infection by Streptococcus pneumoniae requires measurement of serotype
specific functional antibodies. We describe the development and validation of a
viable pneumococcal opsonophagocytosis assay (OPA) that can be used for routine
serological analysis of paediatric immune responses after immunization. OPA
seropositivity (%> or =8 threshold) reflected well invasive pneumococcal disease
(IPD) effectiveness. In contrast, the 22F inhibition ELISA seropositivity (%> or
=0.20microg/ml threshold) overestimated (19F) or underestimated (6B, 23F, 6A) IPD
effectiveness for several serotypes. The seropositivity as estimated by a
standardized and highly reproducible OPA was predictive for the serotype-specific
IPD efficacy of pneumococcal conjugate vaccines.
PMID- 17034908
TI - Animal models for protein pneumococcal vaccine evaluation: a summary.
AB - This paper summarizes the discussion and viewpoints from a recent meeting
regarding the use of animal models for pneumococcal protein vaccines. A wide
spectrum of workers in this field met to discuss the animal species to be used in
models, the approach of passive and active protection, the characteristics of
challenge pneumococcal strains, inducing disease syndromes by a variety of routes
of challenge, the determination of specific endpoints to assess effectiveness,
the correlates of protection and other details of experimental design and
analysis. Vaccine regulatory aspects were discussed. The document concludes with
a series of questions that remain to be investigated.
PMID- 17034909
TI - Establishing the health and economic impact of influenza vaccination within the
European Union 25 countries.
AB - BACKGROUND: In 2003, the World Health Assembly (WHA) issued a resolution for
prevention and control of influenza pandemics and annual epidemics, which urges
the European Union 25 (EU-25) Member States to (1) establish and implement
strategies to increase vaccination coverage of all people at high risk, including
the elderly and people with underlying disease, with the goal of attaining
vaccination coverage of the elderly population of at least 50% by 2006 and 75% by
2010; (2) to assess the disease burden and economic impact of annual influenza
epidemics as a basis for framing and implementing influenza prevention policies.
This resolution was reinforced by the European Union (EU), where Member States
agreed to make additional efforts to improve uptake on their territory in
accordance with their own recommendations and to achieve the World Health
Organisation (WHO) target of 75% in high risk groups before 2010. It was also
noted that the changing demographic profile of the EU population would result in
an increasing number of elderly people falling within the current target groups.
OBJECTIVES: To establish the number of people who may be eligible for influenza
vaccination in the EU, and estimate the costs and consequences of not vaccinating
this population for five EU Member States, France, Germany, Italy, Spain, and the
UK. METHODS: A mathematical model has previously been developed, in which vaccine
distribution data are combined with demographic and health economics data to
model the public health consequences of influenza and possible intervention
strategies. We have extended that model using specific EU-25 demographic data on
populations at risk of influenza during the inter-pandemic period. For each
country, the total population and age breakdown was calculated to estimate the
percentage of the population that falls under the WHA recommendations. Other
target groups for influenza vaccination were identified by analysing estimating
the proportion of the population with respiratory or cardiovascular related
diseases, diabetes, AIDS or transplantation, as well as health care
professionals. Target population size and possible vaccination coverage rates
across the EU-25 Member States, along with the potential cost and health
consequence impact is estimated. RESULTS: For the EU-25, it was estimated that up
to 49.1% of the population (or 223.4 million people) should be vaccinated against
influenza. This ranged from 41.6% in Cyprus to 56.4% in the UK. There were, on
average, 174 vaccine doses distributed per 1000 population within the EU-25,
which leads to an average vaccination rate of the target population of 35.4%
based on current supply constraints. As a consequence, up to 144.4 million people
who could be considered "at risk" may not currently be vaccinated. Implementing a
100% vaccination rate programme for all risk groups across the EU-25 would lead
to an estimated reduction of number of influenza cases of 7.22 million, 1.96
million reduced PCP visits for influenza treatment, 796,743 less hospital
admissions and 68,537 fewer influenza related deaths for all EU-25 countries. The
implementation of a 100% vaccination rate programme for all risk groups in
France, Germany, Italy, Spain and UK would require an additional 1.52 billion
Euro. This would result in estimated savings of 39.45 million Euro of reduced
primary care visits and further savings of 1.59 billion Euro in reduced
hospitalisations respectively in these countries. CONCLUSIONS: There is a gap
between current vaccination coverage and the EU recommendations. The public
health consequences of low vaccination coverage include increased morbidity,
hospitalisations and mortality associated with influenza-related complications.
This model is a powerful tool to: (1) support EU public health officials in
implementing recommendations; (2) to visualize the need for increased vaccination
rates for better influenza control; (3) the consequences of low vaccine coverage.
PMID- 17034910
TI - Reverse radial artery bone flap reconstruction of segmental metacarpal losses.
AB - A vascularised bone segment of the distal radius was harvested as a distally
based flap to treat segmental metacarpal bone loss in three patients. One
reconstruction followed resection of a giant cell tumour excision and the other
two were to replace traumatic bone loss. The bone defects were in the second
metacarpal in two cases and in the second and third metacarpal in one case and
included three shaft and one distal metacarpal reconstruction. The mean length of
the metacarpal defects was 6 cm. All of the flaps survived and no complications
occurred at the donor site. Clinical and radiological union was established in
all cases after an average of 3 months.
PMID- 17034911
TI - Diaphyseal non-union in the distal phalanx of a child.
AB - Non-union after finger fracture is an infrequent complication. Although well
described in adults, there are few reported cases in children. We describe a 6
year-old boy who presented with a non-union of the diaphysis of the distal
phalanx three years after a finger tip crush injury.
PMID- 17034912
TI - The effect of short-term dependency and immobility on skin temperature and colour
in the hand.
AB - The effects of short-term dependency and immobility on skin temperature were
assessed in two experiments. In the first study, ten volunteers hung their left
arm dependent and motionless while using their right hand for light office work.
After 30 minutes, the dependent left hands were cooler (mean=0.9 degrees C: 95%
CI=0.7-1.1) than the active right hands and exhibited a deeper colour with
significantly increased green intensity (P=0.03) as assessed on digital images.
In the second study, seven volunteers submerged both their hands in water at 15
degrees C for 15 minutes. The left arm was then left dependent and motionless
while the right hand was placed on the table and its fingers were flexed and
extended every 10 seconds. The left hands remained cooler than the right and were
a median of 3.6 (range 2.9-4.5) degrees C cooler after 60 minutes. These studies
demonstrate that skin temperature and colour differences between the hands, which
are sometimes used to support the diagnosis of CRPS-1, can be produced and
maintained by short-term immobility and dependency of the hand.
PMID- 17034913
TI - The trapezium: a new location for an aneurysmal bone cyst.
PMID- 17034914
TI - Halogenated organic compounds in archived whale oil: a pre-industrial record.
AB - To provide additional evidence that several halogenated organic compounds (HOCs)
found in environmental samples are natural and not industrially produced, we
analyzed an archived whale oil sample collected in 1921 from the last voyage of
the whaling ship Charles W. Morgan. This sample, which pre-dates large-scale
industrial manufacture of HOCs, contained two methoxylated polybrominated
diphenyl ethers (MeO-PBDEs), five halogenated methyl bipyrroles (MBPs), one
halogenated dimethyl bipyrrole (DMBP), and tentatively one dimethoxylated
polybrominated biphenyl (diMeO-PBB). This result indicates, at least in part, a
natural source of the latter compounds.
PMID- 17034915
TI - Integrated effects of air pollution and climate change on forests: a northern
hemisphere perspective.
AB - Many air pollutants and greenhouse gases have common sources, contribute to
radiative balance, interact in the atmosphere, and affect ecosystems. The impacts
on forest ecosystems have been traditionally treated separately for air pollution
and climate change. However, the combined effects may significantly differ from a
sum of separate effects. We review the links between air pollution and climate
change and their interactive effects on northern hemisphere forests. A
simultaneous addressing of the air pollution and climate change effects on
forests may result in more effective research, management and monitoring as well
as better integration of local, national and global environmental policies.
PMID- 17034916
TI - Smoking, traumatic event exposure, and post-traumatic stress: a critical review
of the empirical literature.
AB - The current review critically examines the extant empirical literature focused on
the associations among cigarette smoking, trauma, and post-traumatic stress.
Inspection of the extant literature suggests that smoking rates are significantly
higher among persons exposed to a traumatic event relative to those without such
exposure. Moreover, smoking rates appear particularly high among persons with
post-traumatic stress disorder (PTSD). In terms of the direction of this
relation, evidence most clearly suggests that post-traumatic stress is involved
in the development of smoking. Significantly less is known about the role of
trauma and PTSD in terms of cessation outcome. Limitations of extant work,
clinical implications, and key directions for future study are delineated.
PMID- 17034917
TI - Relationship between machine-derived smoke yields and biomarkers in cigarette
smokers in Germany.
AB - In order to determine whether smokers of cigarettes in the contemporary yield
ranges of the German market (0.1-1.0mg nicotine, 1-10mg tar) differ in their
actual exposure to various smoke constituents, we performed a field study with
274 smokers and 100 non-smokers. The following biomarkers were determined: In 24
h urine: Nicotine equivalents (molar sum of nicotine, cotinine, trans-3'
hydroxycotinine and their respective glucuronides), 4-(methylnitrosamino)-1-(3
pyridyl)-1-butanol (NNAL, metabolite of the tobacco-specific nitrosamine 4
(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NNK), 3-hydroxypropylmercapturic
acid (metabolite of acrolein), trans,trans-muconic acid, S-phenylmercapturic acid
(metabolites of benzene), 1-hydroxypyrene (metabolite of pyrene); in saliva:
Cotinine and trans-3'-hydroxycotinine; in exhaled air: Carbon monoxide; in blood:
Methyl-, hydroxyethyl-, cyanoethyl- (biomarker of acrylonitrile) and
carbamoylethylvaline (biomarker of acrylamide) hemoglobin adducts. All biomarkers
were found to be significantly higher in smokers compared to non-smokers and
showed strong correlations with the daily cigarette consumption. Biomarker levels
and per cigarette increases in smokers were at most weakly related to the machine
derived smoke yields. It is concluded that machine-derived yields of cigarettes
from the contemporary German cigarette market have little or no impact on the
actual smoking-related exposure determined by suitable biomarkers.
PMID- 17034918
TI - Dignity and health: a review.
AB - Attention to dignity is thriving in health. However, much of this recent
discourse ignores the broader scholarship pertaining to dignity. The purpose of
this review is to synthesize a wide range of multidisciplinary writing in order
to put recent discussions of dignity and health into a broader context. The
review explicates two main meanings of dignity-human dignity and social dignity,
and looks at how these two ideas are used in the arenas of human rights, law,
social justice, bioethics, and clinical care, and suggests some implications of
these meanings and uses for health research and advocacy.
PMID- 17034919
TI - Some issues in the provision of adult bereavement support by UK hospices.
AB - This paper considers some issues in the provision of adult bereavement support in
UK hospices. The paper is based on the findings of a multi-method study conducted
in two phases over 30 months (2003-2005) to examine the nature and quality of
adult bereavement support in UK hospices from the perspectives of bereaved people
and professional and volunteer bereavement workers [Field, Reid, Payne, & Relf
(2005). Adult Bereavement Support in Five Hospices in England. Sheffield, UK:
Palliative and End-of-Life Care Research Group, University of Sheffield.
(Available from Professor Payne)]. It discusses the importance of continuity
between pre-bereavement and bereavement support, the integration of bereavement
services within hospices and the involvement of volunteers in bereavement
support. It then discusses the engagement of UK hospices in the broader
development of bereavement support. Although hospices have developed expertise in
supporting bereaved people, our research suggests that they have not had a major
impact on other health service providers, such as general practitioners and
distinct nurses and staff in acute hospital trusts, in this area.
PMID- 17034920
TI - Why psychosis needed something more than just the evolution of language.
PMID- 17034921
TI - Radiological impact of dietary intakes of naturally occurring radionuclides on
Pakistani adults.
AB - Daily dietary intakes of three naturally occurring long-lived radionuclides
(232)Th, (238)U and (40)K were estimated for the adult population of Pakistan
using neutron activation analysis (NAA), inductively coupled plasma mass
spectrometry (ICP-MS) and atomic absorption spectrometry (AAS), respectively. The
daily intakes of (232)Th ranged from 4 to 29 mBq, (238)U ranged from 17 to 82 mBq
and (40)K ranged from 51 to 128 Bq. The geometric means of these intakes were 10
mBqd(-1) for (232)Th, 33 mBqd(-1) for (238)U and 78.5 Bqd(-1) for (40)K. The
measured values give annual committed effective doses of 0.80, 0.53 and 178.75
microSvyr(-1) for (232)Th, (238)U and (40)K, respectively to Pakistani
population. The net radiological impact of these radionuclides is 180.08
microSvyr(-1). This value gives cancer risk factor of 4.5 x 10(-4) and loss of
life expectancy of 0.87 days only. Whereas ICRP cancer risk factor for general
public is 2.5 x 10(-3) and total risk involve from the all natural radiation
sources based on global average annual radiation dose of 2.4 mSvyr(-1) is 6.0 x
10(-3). The estimated cancer risk shows that probability of increase of cancer
risk from daily Pakistani diet is only a minor fraction of ICRP values.
Therefore, the diet does not pose any significant health hazard and is considered
radiologically safe for human consumption.
PMID- 17034922
TI - Detection of micronucleus and abnormal nucleus in erythrocytes from the gill and
kidney of Labeo bata cultivated in sewage-fed fish farms.
AB - Determination of genotoxic effect in fish, micronucleus test as well as the study
of the abnormal shape of nuclei is a suitable measure, in which the presence or
absence of genotoxins can be detected in water. In the present study, micronuclei
and abnormal nuclei frequencies were scored in the gill and kidney erythrocytes
of the fish Labeo bata grown in the sewage-fed fish farms of East Calcutta
wetlands. Three experimental sites were chosen, namely, Bantala, Chowbaga and
Chingrihata (basically these sites have sewage-fed fishponds), which were
compared with fishponds of no sewage influence as the control area. Highly
significant differences (P<0.001) were noticed for micronucleus frequencies in
the gill and kidney erythrocytes of experimental fishes, where kidney
erythrocytes showed an increased value than gill erythrocytes without any
statistical differences. The frequencies of nuclear abnormalities such as
necrotic cells, apoptotic cells, notch nucleated cells and binucleated cells were
also counted separately for gill and kidney erythrocytes, in which significantly
(P<0.001, P<0.01, P<0.05) increased values were obtained in comparison to control
populations. These genotoxicity results confirmed that the sewage-fed ponds
contain genotoxic metals such as Cr, Zn, Cu, Pb, Mn, Fe through wastewater and
sludge because of the direct use of sewage water without pretreatment which may
lead to health risks among humans through chronic consumption of fish from these
experimental fish ponds. Other vertebrates grown in sewage-fed ponds may also
suffer a certain amount of genotoxic substances.
PMID- 17034923
TI - Effects of diabetes on rabbit kidney and lung CYP2E1 and CYP2B4 expression and
drug metabolism and potentiation of carcinogenic activity of N
nitrosodimethylamine in kidney and lung.
AB - There are limited number of studies regarding the influence of diabetes on the
regulation of cytochrome P450s and associated drug metabolizing enzyme activities
especially in extrahepatic tissues such as kidney. However, there is almost no
such study in lung. Alloxan-induced diabetes did not change CYP2B4 expression as
measured with immunoblot analysis and associated enzyme, benzphetamine N
demethylase, activity in rabbit kidney and lung. Induction of cytochrome P4502E1
by diabetes was identified by immunochemical detection on Western blots in the
lung and kidney microsomes of rabbits. In parallel to CYP2E1 induction, aniline 4
hydroxylase and p-nitrophenol hydroxylase activities were markedly increased in
diabetic rabbit lung and kidney. CYP2B4 and CYP2E1 dependent drug metabolism did
not show any tissue variation in diabetic rabbit. These findings are in contrast
to those of rats, mice and hamster. The results of the present work, in
combination with those of the previous work [Arinc, E., Arslan, S., Adali, O.,
2005. Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and
associated drug metabolizing enzyme activities in rabbit liver. Arch. Toxicol.
79, 427-433], indicate the existence of species-dependent response of CYP
dependent drug metabolizing enzymes to diabetes. A procarcinogen and food
contaminant, N-nitrosodimethylamine (NDMA), is converted to its carcinogenic form
after it is activated with NDMA N-demethylase. In the current study, a
statistically significant increase of liver, kidney and lung NDMA N-demethylase
activity associated with CYP2E1 was shown in diabetic rabbit. Thus, it is
expected that, the risk of nitrosamine induced carcinogenesis will be greater in
liver, kidney and lung of the diabetic subjects.
PMID- 17034925
TI - Protection against nonylphenol-induced cell death by DJ-1 in cultured Japanese
medaka (Oryzias latipes) cells.
AB - The Japanese medaka (Oryzias latipes) has been used to investigate diverse
aspects of toxicology, genetics and developmental biology and to monitor
biological changes caused by endocrine disruptors. In this study, we analyzed a
medaka homolog of human DJ-1 (meDJ-1) in cultured medaka cells into which
nonylphenol (NP) was added. Like human DJ-1, meDJ-1 was found to be oxidized by
treatment with H(2)O(2) and its pI was shifted to acidic points. NP was found to
induce cell death with kinetics similar to that of H(2)O(2) in cultured medaka
OLHE-13 cells. After OLHE-13 cells had been treated with sub-lethal
concentrations of H(2)O(2) and NP, production of reactive oxygen species and
oxidation of meDJ-1 were observed. meDJ-1 knockdown by short interfering RNA
rendered OLHE-13 cells susceptible to H(2)O(2) and NP-induced cell death,
suggesting a protective role of DJ-1 against oxidative stress-induced cell death
in medaka cells. These results suggest that meDJ-1 is a suitable biomarker for
oxidative stress reactions in medaka.
PMID- 17034924
TI - A 90-day dietary study on kappa carrageenan with emphasis on the gastrointestinal
tract.
AB - Groups of Fischer 344 rats (20/sex/group) received control or treated diets at
levels of 0, 25,000 or 50,000 ppm kappa carrageenan with a molecular weight range
(Mw) of 196,000-257,000 Da for 90 days. The Low Molecular Weight Tail (LMT)
ranged between 1.9% and 12.0%<50 kDa (mean 7%) based on the results of a program
initiated to develop a validated analytical method to measure the LMT. This is
the first GLP dietary study in which carrageenan is characterized by percentage
LMT. Clinical examinations were performed daily. Individual food consumption/body
weight measurements were made weekly. Ophthalmic exam was conducted prior to and
at the end of treatment. Hematology/serum chemistry and urinalysis evaluations
were done at necropsy, as were organ weight determinations for adrenals, brain,
heart, kidneys, liver, ovaries, spleen, testes and thyroid with parathyroids.
Full histopathological evaluation of organs was conducted on the control and
50,000 ppm groups, including hematoxylin-eosin-stained cross sections of paraffin
embedded rolled colon. Clinical signs were limited to soft feces in high dose
rats and to a lesser extent in low dose rats. There were no treatment-related
effects on body weights, urinalysis, hematology or clinical chemistry parameters,
or on organ weights or ophthalmic, macroscopic or microscopic findings. The
gastrointestinal tract appeared normal in detailed histopathological evaluation
using the Swiss roll technique. The NOAEL is 50,000 ppm in the diet (mean
calculated test material consumption of 3394+/-706 mg/kg/day in males, 3867+/-647
mg/kg/day in females). The results of the study provide evidence that it is not
necessary to characterize carrageenan by a specification for LMT (less than 5%
below 50 kDa) as has been done in Commission Directive 2004/45/EC of 16 April
2004 (Commission Directive, 2004/45/EC of 16 April 2004 amending Directive
96/77/EC laying down specific purity criteria on food additives other than colors
and sweeteners. Official Journal of European Union 20 April, 2004, L113/19
L113/21).
PMID- 17034927
TI - His164 regulates accessibility to the active site in fungal 17beta-hydroxysteroid
dehydrogenase.
AB - 17beta-Hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17beta
HSDcl) is an NADPH-dependent member of the short-chain dehydrogenase/ reductase
superfamily. To study the catalytic properties of this enzyme, we prepared
several specific mutations of 17beta-HSDcl (Tyr167Phe, His164Trp/Gly, Tyr212Ala).
Wild-type 17beta-HSDcl and the 17beta-HSDcl mutants were evaluated by
chromatographic, kinetic and thermodynamic means. The Tyr167Phe mutation resulted
in a complete loss of enzyme activity, while substitution of His164 with Trp and
Gly both resulted in higher specificity number (V/K) for the steroid substrates,
which are mainly a consequence of easier accessibility of steroid substrates to
the active-site hollow under optimized conditions. The Tyr212Ala mutant showed
increased activity in the oxidative direction, which appears to be a consequence
of increased NADPH dissociation. The kinetic characterizations and thermodynamic
analyses also suggest that His164 and Tyr212 in 17beta-HSDcl have a role in the
opening and closing of the active site of this enzyme and in the discrimination
between oxidized and reduced coenzyme.
PMID- 17034926
TI - Class II composite restorations with metallic and translucent matrices: 2-year
follow-up findings.
AB - OBJECTIVE: The aim of this randomized, clinical study was to evaluate the
performance of composite restorations placed with two matrix and wedge systems
after a 2-year follow-up. METHODS: Twenty-three patients were selected, and
received at least two Class II restorations, one with metallic matrix and wooden
wedge and other with polyester matrix and reflective wedge. One dentist placed
all the 109 restorations. All cavities were restored using Single Bond and P-60
(3M ESPE), according to manufacturer's instructions. In the metal matrix group,
polymerization was performed from occlusal, and in the polyester group, through
the reflective wedge. Restorations were evaluated at baseline and after 12 and 24
months by the modified USPHS criteria, and data were analyzed with Mann-Whitney
and Wilcoxon Signed Rank tests (alpha=0.05). RESULTS: Fifteen subjects and 78
restorations were re-evaluated after 24 months. A significant decrease in the
quality of cervical adaptation and proximal contacts by radiographic evaluation
was evidenced (p<0.05), but no differences between the two matrix systems were
detected (p>0.05). In the clinical evaluation there were no significant
differences between matrices after 2 years (p>0.05). A compromising of marginal
adaptation, marginal staining and proximal contacts aspects for both matrix
systems was evidenced, and restorations placed with translucent matrices showed
loss of color stability (p<0.05). CONCLUSIONS: Whereas restorations presented
some clinical aspects somewhat compromised after 2 years, the matrix and wedge
systems evaluated showed similar clinical performance.
PMID- 17034929
TI - Comment on "Human papillomavirus in the oral mucosa of women with genital human
papillomavirus lesions" [Eur. J. Obstet. Gynecol. Reprod. Biol. 126 (2006) 104
106].
PMID- 17034928
TI - Respiratory sinus arrhythmia and diseases of aging: obesity, diabetes mellitus,
and hypertension.
AB - Associations between respiratory sinus arrhythmia (RSA) and several chronic
diseases, including obesity, diabetes mellitus, and hypertension, have been
documented in recent years. Although most evidence suggests reduced RSA is the
result of chronic disease rather than the cause, some studies have documented
reduced RSA among at-risk individuals prior to disease onset. These results raise
the possibility that decreased vagal tone may play a role in the pathogenesis of
certain chronic diseases. Presented here is a brief overview of studies which
examine the relationship between vagal tone, as measured by RSA and baroreflex
gain, and diseases of aging, including obesity, diabetes mellitus, and
hypertension. Mechanisms by which vagal tone may be related to disease processes
are discussed. In addition, we present results from a population-based study of
RSA and hypertension in older adults. Consistent with previous studies, we found
an inverse relationship between RSA and age, cigarette use, and diabetes. In
logistic regression models which control for age, cigarette use, and diabetes, we
found RSA was a significant negative predictor of hypertension. We conclude that
the relationship between RSA and hypertension is somewhat independent of the age
related decline in parasympathetic activity.
PMID- 17034930
TI - An integrated approach to modeling resource utilization for rural communities in
developing countries.
AB - Resource consumption in developing countries has been the focus of a considerable
amount of research. What has been understudied however, has been the feedback
affects of resource consumption on resource availability to both households and
communities. Heavy reliance on natural resources and intensive smallholder
agriculture common to many rural communities in developing countries has forced
people to fulfill short-term needs to the detriment of long-term ecological and
livelihood sustainability. This paper introduces a conceptual framework to
examine how individuals and households fulfill daily caloric needs and the
aggregate effects on resource availability and consumption. Data were collected
from a large number of published case studies of rural land-use dynamics, growth
and yield models, and human livelihoods were reviewed from scientific journals,
reports published by NGOs, and government reports. Using inputs defined by the
user, the model tracks annual fuelwood and agricultural land use based on meeting
individual energy demands. A case-study-based analysis was patterned after
smallholder agriculturalists at the family and community level. Three scenarios
are presented in this paper using data from Uganda to illustrate the application
of this model.
PMID- 17034931
TI - Testosterone and prostate cancer.
PMID- 17034932
TI - Relationship between vascular damage degrees and endothelial progenitor cells in
patients with erectile dysfunction: effect of vardenafil administration and PDE5
expression in the bone marrow.
AB - OBJECTIVES: To evaluate the levels of circulating progenitor cells (PCs) and the
effect of a single dose of vardenafil 20mg on the number of these cells in men
with erectile dysfunction (ED) and various degree of vascular injury at the
carotid artery level. METHODS: Sixty-eight patients with ED and various degree of
carotid damage, and 25 controls were enrolled. Patients were divided into three
groups according to their intima media thickness (IMT) status (normal, mild
increase, or plaque). All subjects received vardenafil 20mg, and evaluation of
the number of circulating PCs was performed at baseline and 4h after vardenafil
administration. An RNA expression analysis of phosphodiesterase type 5 (PDE5) on
bone marrow was also performed. RESULTS: We found a significant reduction of
circulating PCs in ED patients with respect to controls and a reduction in PC
counts in patients with mild IMT increase or plaque, but not in those with normal
IMT. Four hours after vardenafil administration we observed an increase in the
number of PCs in all patients and controls. Reverse transcriptase-polymerase
chain reaction analysis showed that human bone marrow expresses PDE5 messenger
RNA. CONCLUSIONS: Patients with ED and a low number of circulating PCs may be
considered at increased risk for an endothelial dysfunction. An impaired response
to vardenafil stimulus may be proposed as a surrogate marker of a patient's
endothelial regenerative ability.
PMID- 17034933
TI - The prostate cancer prevention trial and its messages.
PMID- 17034934
TI - From membranes to systems: self-configuration and self-replication in membrane
systems.
AB - Membrane systems are purely abstract computational models afar inspired by
biological cells, their membranes, and their biochemistry. The inherently
parallel nature of membrane systems makes them obviously highly inefficient to
execute on a sequential von Neumann computer architecture and in addition,
programming a membrane system is often a painstakingly difficult undertaking. The
main goal of this paper is to provide some key elements for bringing membrane
systems from the abstract model closer to a genuine, novel, and unconventional in
silico computer architecture. In particular, we will address the mechanisms of
self-configuration and self-replication on a macroscopic level and will discuss
some general issues related to genuine hardware realizations on the microscopic
level.
PMID- 17034935
TI - Directional hearing in a silicon cricket.
AB - Phonotaxis is the ability to orient towards or away from sound sources. Crickets
can locate conspecifics by phonotaxis to the calling (mating) song they produce,
and can evade bats by negative phonotaxis from echolocation calls. The behaviour
and underlying physiology have been studied in some depth, and the auditory
system solves this complex problem in a unique manner. Experiments conducted on a
simulation model of the system indicated that the mechanism output a directional
signal to sounds ahead at calling song frequency and to sounds behind at
echolocation frequencies. We suggest that this combination of responses helps
simplify later processing in the cricket. To further explore this result, an
analogue, very large scale integrated (aVLSI) circuit model of the mechanism was
designed and built; results from testing this agreed with the simulation. The
aVLSI circuit was used to test a further hypothesis about the potential
advantages of the positioning of the acoustic inputs for sound localisation
during walking. There was no clear advantage to the directionality of the system
in their location. The aVLSI circuitry is now being extended to use on a robot
along with previously modelled neural circuitry to better understand the complete
sensorimotor pathway.
PMID- 17034936
TI - Landfill leachate treatment with ozone and ozone/hydrogen peroxide systems.
AB - In the search for an efficient and economical method to treat a leachate
generated from a controlled municipal solid waste landfill site (Jebel Chakir) in
the region of greater Tunis in Tunisia, ozone alone and ozone combined with
hydrogen peroxide were studied. The leachate was characterised by high COD, low
biodegradability and intense dark colour. A purpose-built reactor, to avoid
foaming, was used for the study. It was found that ozone efficacy was almost
doubled when combined with hydrogen peroxide at 2g/L but higher H(2)O(2)
concentrations gave lower performances. Enhancement in the leachate
biodegradability from about 0.1 to about 0.7 was achieved by the O(3)/H(2)O(2)
system. Insignificant changes in pH that may due to buffering effect of
bicarbonate was found. A small decrease in sulphate concentrations were also
observed. In contrast, chloride concentration declined at the beginning of the
experiment then increased to reach its initial value. Estimates of the operating
costs were made for comparison purposes and it was found that the O(3)/H(2)O(2)
system at 2g/L H(2)O(2) gave the lowest cost of about 3.1TND( approximately
2.3USD)/kgCOD removed.
PMID- 17034937
TI - Application of Fenton oxidation to cosmetic wastewaters treatment.
AB - The removal of organic matter (TOC and COD) from a cosmetic wastewater by Fenton
oxidation treatment has been evaluated. The operating conditions (temperature as
well as ferrous ion and hydrogen peroxide dosage) have been optimized. Working at
an initial pH equal to 3.0, a Fe(2+) concentration of 200 mg/L and a H(2)O(2)
concentration to COD initial weight ratio corresponding to the theoretical
stoichiometric value (2.12), a TOC conversion higher than 45% at 25 degrees C and
60% at 50 degrees C was achieved. Application of the Fenton oxidation process
allows to reach the COD regional limit for industrial wastewaters discharges to
the municipal sewer system. A simple kinetic analysis based on TOC was carried
out. A second-order equation describes well the overall kinetics of the process
within a wide TOC conversion range covering up to the 80-90% of the maximum
achievable conversion.
PMID- 17034938
TI - The effect of Fe0/Fe2+/Fe3+ on nitrobenzene degradation in the anaerobic sludge.
AB - The influence of Fe(0)/Fe(2+)/Fe(3+) on the nitrobenzene (NB) degradation in the
anaerobic granular sludge was studied and the results demonstrated that: adding
iron powder into the anaerobic sludge could exert an accelerative effect on the
NB degradation and the degradation rate was faster than that by using iron or the
anaerobic sludge alone. The external addition of Fe(2+)/Fe(3+) exhibited
different influences on the NB degradation depending on the concentrations of
Fe(2+)/Fe(3+) and the solution's pH. When Fe(2+)/Fe(3+) are less than 100 mg/L at
pH 6, Fe(2+)/Fe(3+) inhibited the NB degradation slightly, and when Fe(2+)/Fe(3+)
was 100-200 mg/L, the NB degradation was enhanced. When pH was shifted to 9,
Fe(2+) of lower than 100 mg/L promoted the NB degradation, and 200 mg/L Fe(2+)
inhibit the NB degradation. The synergism of combined use of iron and the
anaerobic sludge in treating NB wastewater was proposed, and adjusting the
concentrations of Fe(2+)/Fe(3+) in the anaerobic sludge according to the pH of
the wastewater could be an effective method to obtain a high removal rate of NB.
PMID- 17034939
TI - Mathematical modelling of 4-chlorophenol inhibition on COD and 4-chlorophenol
removals in an activated sludge unit.
AB - A mathematical model was developed for an activated sludge unit treating 4
chlorophenol (4-CP) containing synthetic wastewater composed of diluted molasses,
urea, KH(2)PO(4) and MgSO(4) with COD and 4-CP contents of 2500 and 500 mg l(-1),
respectively. The model included 4-CP inhibition on COD and 4-CP removals.
Experimental data obtained at different hydraulic residence times (HRT=5-30h) and
sludge ages (SRT, 3-30 days) were used to estimate the kinetic and inhibition
constants for COD and 4-CP removal rates. 4-CP inhibition on COD removal was
negligible while the inhibition on 4-CP removal was significant. The specific
rate constant (k), saturation constant (K(s)) for COD oxidation were found to be
2.64 day(-1) and 559 mg l(-1), respectively. A similar model was used for 4-CP
oxidation in the activated sludge unit and the constants were found to be k'=1.44
day(-1), K'(s)=25.7 mgl(-1), K"(CP)=559 mg l(-1),and K(I,CP)=17 mg l(-1).
Increases in death rate constant because of 4-CP inhibition was also quantified
and the inhibition constants were determined for both COD and 4-CP removals.
Model predictions with the estimated kinetic constants were in good agreement
with the experimental data. Developed model can be used to estimate the
performance of an activated sludge unit treating 4-CP containing wastewater under
the specified experimental conditions.
PMID- 17034940
TI - Studies on the sorption of praseodymium (III), holmium (III) and cobalt (II) from
nitrate medium using TVEX-PHOR resin.
AB - The use of TVEX-PHOR resin for the sorption of praseodymium (III), holmium (III)
and cobalt (II) from nitrate medium was carried out using batch and column
techniques. Various parameters affecting the uptake of these metal ions such as
v/m ratio, pH and the metal ion concentration were separately studied. Effect of
temperature on the equilibrium distribution values has been studied to evaluate
the changes in standard thermodynamic quantities. Experimental results of the
investigated metal ions were found to fit to Freundlich isotherm model over the
entire studied concentration range. Selectivity sequence of the resin for these
metals is Ho>Pr>Co. The recovery of the investigated metals from the loaded resin
is preformed with 0.1M sulphuric acid.
PMID- 17034941
TI - Development of a miniature calorimeter for identification and detection of
explosives and other energetic compounds.
AB - The development of versatile systems capable of providing rapid, portable, and
inexpensive detection of explosives and energetic compounds are critically needed
to offer enhanced levels of protection against current and future threats to
homeland security, as well as satisfying a wide range of applications in the
fields of forensic analysis, emergency response, and industrial hazards analysis.
Calorimetric techniques have been largely overlooked in efforts to develop
advanced chemical analysis technology, largely because of limitations associated
with the physical size of the instruments and the relatively long timescales (>30
min) required to obtain a result. This miniaturized calorimeter circumvents these
limitations, thereby creating a first-of-its-kind system allowing thermal
analysis to be performed in a portable format that can be configured for use in a
variety of field operations with a significantly reduced response time
(approximately 2 min). Unlike current explosives detectors, this system is based
on calorimetric techniques that are inherently capable of providing direct
measurements of energy release potential and therefore do not depend on prior
knowledge of familiar compounds.
PMID- 17034942
TI - Occurrence of disinfection by-products in low DOC surface waters in Turkey.
AB - A total of 29 surface waters from different regions of Turkey were sampled once a
month during 2004. Filtered raw water samples were characterized, chlorinated and
the concentrations of disinfection by-products (DBPs) were measured. All waters
were low in DOC ranging from 0.91 to 4.42 mg/L. The range of annual average
trihalomethanes (THMs) and haloacetic acids (HAAs) concentrations in all waters
was 21-189 and 18-149mug/L, respectively. Total mass contributions of halides in
THMs and HAAs to absorbable organic halides (AOX) ranged between 10 and 56% in
all waters on annual average basis, indicating that significant amounts of other
DBPs are being formed in the majority of the tested waters. A strong linear
correlation was obtained between the concentrations of THMs and HAAs. Rather poor
correlations were found for THMs-AOX and HAAs-AOX levels. For both THMs and HAAs,
chlorinated species dominated over brominated ones since the majority of water
sources had very low bromide levels. While chloroform and trichloroacetic acid
were the major THM and HAA compounds, respectively; the extent of formation and
speciation of DBPs varied greatly by season and water source. No consistent
general trends were observed in terms of seasonal variations in DBP levels,
suggesting that the characteristics of NOM moieties and their chlorine reactivity
vary by season in almost all waters tested.
PMID- 17034943
TI - Synthesis and heavy metal immobilization behaviors of slag based geopolymer.
AB - In this paper, two aspects of studies are carried out: (1) synthesis of
geopolymer by using slag and metakaolin; (2) immobilization behaviors of slag
based geopolymer in a presence of Pb and Cu ions. As for the synthesis of slag
based geopolymer, four different slag content (10%, 30%, 50%, 70%) and three
types of curing regimes (standard curing, steam curing and autoclave curing) are
investigated to obtain the optimum synthesis condition based on the compressive
and flexural strength. The testing results showed that geopolymer mortar
containing 50% slag that is synthesized at steam curing (80 degrees C for 8h),
exhibits higher mechanical strengths. The compressive and flexural strengths of
slag based geopolymer mortar are 75.2 MPa and 10.1 MPa, respectively.
Additionally, Infrared (IR), X-ray diffraction (XRD) and scanning electron
microscopy (SEM) techniques are used to characterize the microstructure of the
slag based geopolymer paste. IR spectra show that the absorptive band at 1086 cm(
1) shifts to lower wave number around 1007 cm(-1), and some six-coordinated Als
transforms into four-coordination during the synthesis of slag based geopolymer
paste. The resulting slag based geopolymeric products are X-ray amorphous
materials. SEM observation shows that it is possible to have geopolymeric gel and
calcium silicate hydrate (C-S-H) gel forming simultaneously within slag based
geopolymer paste. As for immobilization of heavy metals, the leaching tests are
employed to investigate the immobilization behaviors of the slag based geopolymer
mortar synthesized under the above optimum condition. The leaching tests show
that slag based geopolymer mortar can effectively immobilize Cu and Pb heavy
metal ions, and the immobilization efficiency reach 98.5% greater when heavy
metals are incorporated in the slag geopolymeric matrix in the range of 0.1-0.3%.
The Pb exhibits better immobilization efficiency than the Cu in the case of large
dosages of heavy metals.
PMID- 17034944
TI - Biosorption of Reactive Black 5 dye by Penicillium restrictum: the kinetic study.
AB - Biosorption of Reactive Black 5 (RB 5) dye onto dried Penicillium restrictum
biomass was studied with respect to pH, contact time, biosorbent and dye
concentrations. The effect of temperature on the biosorption efficiency was also
carried out and the kinetic parameters were determined. Optimum initial pH,
equilibrium time and biomass concentration for RB 5 dye were found to be 1.0, 75
min and 0.4 g dm(-3) at 20 degrees C, respectively. The maximum biosorption
capacities (q(max)) of RB 5 dye onto dried P. restrictum biomass were 98.33 and
112.50mg (g biomass)(-1) at 175 mg dm(-3) initial dye concentration at 20 and 50
degrees C, respectively, and it was 142.04 mg (g biomass)(-1) at 200 mg dm(-3)
initial dye concentration at 35 degrees C. The results indicate that the
biosorption process obeys a pseudo-second-order kinetic model.
PMID- 17034945
TI - A distinct group of non-cholinergic neurons along the mid-line of the septum and
within the rat medial septal nucleus.
AB - The septum is a critical and integral component of the limbic brain that serves
as a link between diverse brain structures while being necessary for human
cognition and emotionality. A major anatomical component of the septum is
designated as the medial septum/diagonal band of Broca complex (MS/DB). A primary
focus of much research has been to investigate cholinergic neurons within the
MS/DB, as these are the rodent brain's main source of acetylcholine to the cortex
and hippocampus. On the other hand, we have chosen to investigate a specific
group of neurons that lie on the midline of the MS/DB in an area distinguished
anatomically as the medial septal nucleus (MSN). Based on somatic morphology and
electrophysiological characteristics we conclude that these neurons,
characterized into three different types, are non-cholinergic.
PMID- 17034946
TI - High frequency of neurexin 1beta signal peptide structural variants in patients
with autism.
AB - Neuroligins are postsynaptic membrane cell-adhesion molecules which bind to beta
neurexins, a family of proteins that act as neuronal cell surface receptors. To
explore the possibility that structural variants in the beta-neurexin genes
predispose to autism, the coding regions and associated splice junctions of three
beta-neurexin genes were scanned with detection of virtually all mutations-SSCP
(DOVAM-S) in 72 Caucasian patients with autism. In addition, segments of the
neurexin 1beta gene were sequenced in 131 additional Caucasian and 61 Afro
American patients with autism from South Carolina and the Midwest. Two putative
missense structural variants were identified in the neurexin 1beta gene in four
Caucasian patients with autism and not in 535 healthy Caucasian controls (4/203
vs. 0/535, P=0.0056). Initial family data suggest that incomplete penetrance may
occur. In addition, no structural variant was found in the neurexin 2beta gene
and the neurexin 3beta gene. In the context of all available data, we conclude
that mutations of the neurexin 1beta gene may contribute to autism
susceptibility.
PMID- 17034947
TI - Expression analyses of 27 DNA repair genes in astrocytoma by TaqMan low-density
array.
AB - DNA repair systems act to maintain genome integrity in the face of replication
errors, environmental insults, and the cumulative effects of age. The mRNA
expressions of 27 genes of the DNA repair system as well as their correlation
with the clinical characteristics were studied in human astrocytoma. We applied
TaqMan low-density array to investigate the mRNA expressions of 27 DNA repair
genes in 40 astrocytoma tissues (10 of grade II, 10 of grade III, and 20 of grade
IV, according to the WHO Grading System). And the normal brain tissues from 10
non-astrocytoma patients were collected as the control. In addition, correlation
of their mRNA levels with clinical characteristics was also analyzed. We found
that the expression of the 13 genes were significantly (P<0.01) down-regulated in
grade II, III, IV of astrocytoma compared to normal brain tissues, including
ERCC1, ERCC2, ERCC3, ERCC4, MGMT, MLH1, MLH3, NTHL1, OGG1, RAD50, SMUG1, XRCC4
and XRCC5. Meanwhile, we found that the expression of MSH2, MSH6, NUDT1 and XRCC3
were only significantly lower in grade II and III of astrocytoma, and the
expression of MRE11A and MUS81 were only significantly lower in grade III and IV.
But the expression of MPG, MSH3, MUTHY and RAD51 were not changed in any grade of
astrocytoma. Furthermore, we found that the decrease expression of eight genes
was significantly (P<0.05) associated with a poor prognosis, including ERCC3,
ERCC4, MLH3, MRE11A, NTHL1, RAD50, XRCC4 and XRCC5. We suggest that TaqMan low
density array is an effective multivariate technique to examine the expression of
DNA repair genes in astrocytomas, which can be applied to identify tumor-specific
genes. We also suggest that the down-regulation of some DNA repair genes may be
associated with pathogenesis and poor prognosis of astrocytoma.
PMID- 17034948
TI - Interhemispheric transfer time and structural properties of the corpus callosum.
AB - The present study examined how interhemispheric transfer time (IHTT) is affected
by interindividual differences in corpus callosum (CC) architecture. For this
purpose the CC of 42 healthy male subjects was assessed by applying a combination
of morphological and diffusion-tensor magnetic resonance imaging to characterize
the CC on macro- (midsagittal area) and microstructural level (mean diffusion,
fractional anisotropy). Following the so-called Poffenberger paradigm, IHTT was
determined with both reaction time measures and event-related potentials recorded
in response to stimuli briefly presented to either left or right visual
hemifield. Statistical analysis revealed significant negative correlations
between mean diffusion and IHTT estimates derived from the P100 component (at
O1/O2 electrode pair), particularly in the posterior CC subregion. Interpreting
mean diffusion as an index of microstructural tissue properties, IHTT appears to
be directly related to the structural integrity of the posterior CC.
PMID- 17034949
TI - Fluorescence imaging and investigations of directly labelled chromosomes using
scanning near-field optical microscopy.
AB - Scanning near-field optical microscopy (SNOM) has been successfully employed to
generate high resolution (<100nm) fluorescence images of directly tagged human
chromosomes. Direct tagging, fluorescence in-situ hybridisation processes (with
and without amplification) are investigated and their fluorescence response to
near-field excitation are compared. Using the simultaneous topography mode of
SNOM, chromosome morphology was seen to differ as a result of the two processes;
with chromatin collapse more extensive when the amplified direct tagging
procedure was used. The results are discussed in the context of developing locus
specific direct tags together with high resolution SNOM imaging for the
observation of chromosome aberrations.
PMID- 17034950
TI - Comparison of the activity of selamectin, imidacloprid and fipronil for the
treatment of cats infested experimentally with Ctenocephalides felis felis and
Ctenocephalides felis strongylus.
AB - Twenty adult, domestic short hair cats were randomly allocated into four groups
of five cats and housed in separated cages. Each cat was infested with 25 fleas
Ctenocephalides felis felis and 25 Ctenocephalides felis strongylus and 2 days
later (day 0) the cats in group 1, 2 and 3 received a spot on application of
selamectin, imidacloprid or fipronil, respectively, while the cats in group four
were not treated. The cats were combed 48 h later, the fleas were removed,
counted and their subspecies were determined. All the cats were reinfested with
the same number of the two subspecies of fleas on days 7, 14, 21, 29 and 35. The
efficacy of each treatment was calculated 48 h after each infestation. The mean
number of fleas on the control cats was 16.4 C. f. felis and 13.4 C. f.
strongylus. The three treatments were effective for the first 31 days for C. f.
felis and for the full 37 days for C. f. strongylus. Over the first 31 days, the
efficacy of selamectin ranged from 89 to 100% and 85 to 100% against C. f. felis
and C. f. strongylus, respectively, the efficacy of imidacloprid ranged from 76
to 100% and 92 to 100% and the efficacy of fipronil ranged from 98 to 100% and 97
to 100% against C. f. felis and C. f. strongylus. There were no significant
differences between the control of C. f. felis and C. f. strongylus by the three
products.
PMID- 17034951
TI - Biochemical characterization and molecular cloning of a plasminogen activator
proteinase (LV-PA) from bushmaster snake venom.
AB - The protein (LV-PA) from bushmaster (Lachesis muta muta) venom is a serine
proteinase which specifically activates the inactive proenzyme plasminogen. LV-PA
is a single chain glycoprotein with an apparent molecular mass of 33 kDa that
fell to 28 kDa after treatment with N-Glycosidase F (PNGase F). Approximately 93%
of its protein sequence was determined by automated Edman degradation of various
fragments derived from a digestion with trypsin. A cDNA library of L. m. muta was
constructed to generate expressed sequence tags (ESTs) and the plasminogen
activator precursor cDNA was sequenced. The complete amino acid sequence of the
enzyme was deduced from the cDNA sequence. LV-PA is composed of 234 residues and
contains a single asparagine-linked glycosylation site, Asn-X-Ser, bearing sugars
that account for approximately 10% of the enzyme's total molecular mass of 33
kDa. The sequence of LV-PA is highly similar to the plasminogen activators (PAs)
TSV-PA from Trimeresurus stejnegeri venom and Haly-PA from Agkistrodon halys.
Furthermore, the mature protein sequence of LV-PA exhibits significant similarity
with other viperidae venom serine proteinases which affect many steps of
hemostasis, ranging from the blood coagulation cascade to platelet function. The
Michaelis constant (Km) and the catalytic rate constant (kcat) of LV-PA on four
chromogenic substrates were obtained from Lineweaver-Burk plots. In addition, we
used an indirect enzyme-linked immunoabsorbent assay (ELISA) to explore the
phylogenetic range of immunological cross-reactivity (using antibodies raised
against LV-PA) with analogous serine proteinases from two viperidae venoms and
mammals.
PMID- 17034952
TI - Surgical treatment of oral burn contractures with assistance of external
distractors: report of two cases.
PMID- 17034953
TI - Targeted therapy in advanced non-small cell lung cancer (NSCLC): where do we
stand?
AB - Cytotoxic chemotherapy has helped improve the outcomes in patients with advanced
non-small cell lung cancer (NSCLC), but we seem to have reached a plateau with
respect to the benefit obtained. Also, a large subset of elderly patients and
those with a poor performance status cannot tolerate these drugs at recommended
doses. There is a growing need to incorporate newer drugs with different
mechanisms of action and better safety profile. The epidermal growth factor
receptor family (EGFR) and vascular endothelial growth factor (VEGF) have been
identified as potential targets and agents acting specifically against these
targets have been developed with the hope of improving outcomes. Although recent
data with the small molecule EGFR tyrosine kinase inhibitors have been
disappointing, there have been instances of dramatic responses thereby raising
questions about the ideal patient to whom these drugs should be administered.
Cetuximab, the anti-EGFR antibody has shown promising results. Bevacizumab, the
anti-VEGF antibody was the first drug to demonstrate a survival benefit in first
line treatment when added to chemotherapy. This review will briefly discuss the
important trials using these targeted agents in advanced NSCLC.
PMID- 17034954
TI - Oral progesterone decreases saccadic eye velocity and increases sedation in
women.
AB - The aim of this study was to investigate the neurophysiological and behavioural
effects of a single dose of progesterone in women. Allopregnanolone is a
metabolite of progesterone and a potent positive modulator of the GABA(A)
receptor and produces sedative and anxiolytic effects. This study was designed to
examine the effect of oral progesterone and the metabolite allopregnanolone in
women. Women (n=15) in their follicular phase received oral progesterone (400mg)
or placebo. Dependent measures included plasma levels of progesterone and
allopregnanolone, saccadic eye velocity (SEV), subjective ratings (visual
analogue scales), and reaction time. Administration of progesterone decreased SEV
and increased sedation. This effect is probably due to enhanced GABA activity.
PMID- 17034956
TI - Laser iridotomy for intraoperative floppy iris syndrome.
PMID- 17034955
TI - Prediction of treatment response by HPA-axis and glucocorticoid receptor
polymorphisms in major depression.
AB - OBJECTIVE: We investigated whether treatment response is predicted by
hypothalamus-pituitary-adrenal (HPA) axis parameters, or by genetic polymorphisms
in the glucocorticoid receptor (GR), that regulates its feedback. METHODS: Ninety
eight outpatients completed 8 weeks of paroxetine treatment. Treatment response
was defined as a 50% decrease in Hamilton Rating Scale for depression (HRSD)
ratings. At baseline, 24h urinary cortisol excretion, and cortisol and ACTH
concentrations in a DEX/CRH test were measured. The presence of polymorphisms in
the GR DNA sequence (BclI, ER22/23EK, N363S) was determined. Prediction of
treatment response was analysed by calculating response rates per tertile of an
HPA-axis parameter and per GR genotype. RESULTS: The response rate in the high
ACTH tertile was significantly lower as compared to the intermediate tertile, but
not compared to the low tertile (response rates from high to low tertile: 33%,
67% and 42%). Carriers of the BclI polymorphism had higher ACTH values than non
carriers (baseline ACTH: 3 versus 5ng/l, p=0.02) and showed a trend towards lower
decrease of HRSD rates than non-carriers (HRSD decrease: 8 versus 11,
respectively, p=0.07). In a subgroup of BclI carriers, patients in the high ACTH
tertile had a lower decrease in HRSD and lower response rates than patients in
the low ACTH tertiles (HRSD decrease from high to low tertile: 5, 9 and 11,
p<0.01). CONCLUSION: The results suggest that hyperactivity of the HPA-axis
predict worse treatment outcome. The BclI polymorphism explains, in part, DEX/CRH
test results and tends to be associated with worse treatment outcome.
PMID- 17034957
TI - Cytohistopathologic hybrid renal cell carcinoma with papillary and clear cell
features.
AB - Clear cell (CRCC) and papillary (PRCC) renal cell carcinomas (RCC) are the two
most frequent subtypes of RCC. In this study, we studied RCC which displayed a
hybrid morphology with areas of PRCC and CRCC or which contained papillary
structures with clear cell changes (CCC). Consecutive cases of RCC collected over
a 12-year period were reviewed to identify RCC with papillary structures and a
possible admixture between CRCC and non-oncocytic PRCC. Special stains for
glycogen and immunostaining for cytokeratin 7 were applied to sections containing
both areas of classical PRCC and PRCC with CCC. Of the total of 541 RCC
retrieved, there were 68 non-oncocytic RCC having papillary structures that could
be grouped into: (a) group 1 (15 cases), CRCC with areas of papillary formation;
(b) group 2a (9 cases), PRCC with extensive CCC with areas of foamy epithelial
cells or macrophages; (c) group 2b (18 cases), RCC with areas of classical PRCC
with focal CCC; and (d) group 3 (26 cases), RCC with features of groups 2a and 2b
and containing areas of classical CRCC. There was a high rate (12/68) of
sarcomatous transformation in the study cases. Groups 2 and 3 were associated
with a higher rate of vascular invasion, distant metastasis, and mortality than
classical PRCC and a higher rate of lymph node metastasis than CRCC. Our study
identifies two groups of RCC (referred to as groups 2 and 3) that exhibit
characteristic cytohistopathologic hybrid features that set them apart from
classical RCC. This type of hybrid tumor seems to be associated with a more
aggressive biologic behavior, and its recognition may facilitate the
classification of RCC with ambiguous morphology.
PMID- 17034958
TI - The behavioral economics of will in recovery from addiction.
AB - Behavioral economic studies demonstrate that rewards are discounted
proportionally with their delay (hyperbolic discounting). Hyperbolic discounting
implies temporary preference for smaller rewards when they are imminent, and this
concept has been widely considered by researchers interested in the causes of
addictive behavior. Far less consideration has been given to the fact that
systematic preference reversal also predicts various self-control phenomena,
which may also be analyzed from a behavioral economic perspective. Here we
summarize self-control phenomena predicted by hyperbolic discounting,
particularly with application to the field of addiction. Of greatest interest is
the phenomenon of choice bundling, an increase in motivation to wait for delayed
rewards that can be expected to result from making choices in whole categories.
Specifically, when a person's expectations about her own future behavior are
conditional upon her current behavior, the value of these expectations is added
to the contingencies for the current behavior, resulting in reduced impulsivity.
Hyperbolic discounting provides a bottom-up basis for the intuitive learning of
choice bundling, the properties of which match common descriptions of willpower.
We suggest that the bundling effect can also be discerned in the advice of 12
step programs.
PMID- 17034959
TI - Newly established in vitro system with fluorescent proteins shows that abnormal
expression of downstream prion protein-like protein in mice is probably due to
functional disconnection between splicing and 3' formation of prion protein pre
mRNA.
AB - We and others previously showed that, in some lines of prion protein (PrP)
knockout mice, the downstream PrP-like protein (PrPLP/Dpl) was abnormally
expressed in brains partly due to impaired cleavage/polyadenylation of the
residual PrP promoter-driven pre-mRNA despite the presence of a poly(A) signal.
In this study, we newly established an in vitro transient transfection system in
which abnormal expression of PrPLP/Dpl can be visualized by expression of the
green fluorescence protein, EGFP, in cultured cells. No EGFP was detected in
cells transfected by a vector carrying a PrP genomic fragment including the
region targeted in the knockout mice intact upstream of the PrPLP/Dpl gene. In
contrast, deletion of the targeted region from the vector caused expression of
EGFP. By employing this system with other vectors carrying various deletions or
point mutations in the targeted region, we identified that disruption of the
splicing elements in the PrP terminal intron caused the expression of EGFP.
Recent lines of evidence indicate that terminal intron splicing and
cleavage/polyadenylation of pre-mRNA are functionally linked to each other. Taken
together, our newly established system shows that the abnormal expression of
PrPLP/Dpl in PrP-knockout mice caused by the impaired cleavage/polyadenylation of
the PrP promoter-driven pre-mRNA is due to the functional dissociation between
the pre-mRNA machineries, in particular those of cleavage/polyadenylation and
splicing. Our newly established in vitro system, in which the functional
dissociation between the pre-mRNA machineries can be visualized by EGFP green
fluorescence, may be useful for studies of the functional connection of pre-mRNA
machineries.
PMID- 17034960
TI - Mavericks, a novel class of giant transposable elements widespread in eukaryotes
and related to DNA viruses.
AB - We previously identified a group of atypical mobile elements designated Mavericks
from the nematodes Caenorhabditis elegans and C. briggsae and the zebrafish Danio
rerio. Here we present the results of comprehensive database searches of the
genome sequences available, which reveal that Mavericks are widespread in
invertebrates and non-mammalian vertebrates but show a patchy distribution in non
animal species, being present in the fungi Glomus intraradices and Phakopsora
pachyrhizi and in several single-celled eukaryotes such as the ciliate
Tetrahymena thermophila, the stramenopile Phytophthora infestans and the
trichomonad Trichomonas vaginalis, but not detectable in plants. This
distribution, together with comparative and phylogenetic analyses of Maverick
encoded proteins, is suggestive of an ancient origin of these elements in
eukaryotes followed by lineage-specific losses and/or recurrent episodes of
horizontal transmission. In addition, we report that Maverick elements have
amplified recently to high copy numbers in T. vaginalis where they now occupy as
much as 30% of the genome. Sequence analysis confirms that most Mavericks encode
a retroviral-like integrase, but lack other open reading frames typically found
in retroelements. Nevertheless, the length and conservation of the target site
duplication created upon Maverick insertion (5- or 6-bp) is consistent with a
role of the integrase-like protein in the integration of a double-stranded DNA
transposition intermediate. Mavericks also display long terminal-inverted repeats
but do not contain ORFs similar to proteins encoded by DNA transposons. Instead,
Mavericks encode a conserved set of 5 to 9 genes (in addition to the integrase)
that are predicted to encode proteins with homology to replication and packaging
proteins of some bacteriophages and diverse eukaryotic double-stranded DNA
viruses, including a DNA polymerase B homolog and putative capsid proteins. Based
on these and other structural similarities, we speculate that Mavericks represent
an evolutionary missing link between seemingly disparate invasive DNA elements
that include bacteriophages, adenoviruses and eukaryotic linear plasmids.
PMID- 17034961
TI - Identification and characterization of novel polymorphic LINE-1 insertions
through comparison of two human genome sequence assemblies.
AB - Mobile elements represent a relatively new class of markers for the study of
human evolution. Long interspersed elements (LINEs) belong to a group of
retrotransposons comprising approximately 21% of the human genome. Young LINE-1
(L1) elements that have integrated recently into the human genome can be
polymorphic for insertion presence/absence in different human populations at
particular chromosomal locations. To identify putative novel L1 insertion
polymorphisms, we computationally compared two draft assemblies of the whole
human genome (Public and Celera Human Genome assemblies). We identified a total
of 148 potential polymorphic L1 insertion loci, among which 73 were candidates
for novel polymorphic loci. Based on additional analyses we selected 34 loci for
further experimental studies. PCR-based assays and DNA sequence analysis were
performed for these 34 loci in 80 unrelated individuals from four diverse human
populations: African-American, Asian, Caucasian, and South American. All but two
of the selected loci were confirmed as polymorphic in our human population panel.
Approximately 47% of the analyzed loci integrated into other repetitive elements,
most commonly older L1s. One of the insertions was accompanied by a BC200
sequence. Collectively, these mobile elements represent a valuable source of
genomic polymorphism for the study of human population genetics. Our results also
suggest that the exhaustive identification of L1 insertion polymorphisms is far
from complete, and new whole genome sequences are valuable sources for finding
novel retrotransposon insertion polymorphisms.
PMID- 17034962
TI - A systematic analysis of lineage-specific evolution in metabolic pathways.
AB - In a search for the lineage-specific evolution of pathways between human,
chimpanzee, mouse, and rat, orthologous gene families were generated from genome
sequences. For each family, a model-based ratio of nonsynonymous to synonymous
nucleotide substitution rates was calculated. Where the free-ratio model of
individual ratios on each branch was supported, these families were mapped to two
databases of metabolic pathways (KEGG and BioCyc) and the lineage-specific
evolution of pathways was evaluated. The most similar pathway evolution was seen
between mouse and rat, while the evolutionary pattern between human and
chimpanzee was less correlated. Individual pathways in the human lineage were
observed to evolve in a faster, lineage-specific manner, including the pathway
involving arachidonic acid metabolism (identified through the KEGG analysis) and
pyrimidine metabolism (identified through both analyses).
PMID- 17034963
TI - Antimicrobial resistance in Salmonella enterica serovar Dublin isolates from beef
and dairy sources.
AB - Salmonella enterica serovar Dublin (S. Dublin) is a cattle-adapted Salmonella
serovar, so if antimicrobial resistance in S. Dublin arises as a result of
antimicrobial use this most likely occurs within the cattle reservoir without
impact from antimicrobial use in humans. We tested the antimicrobial resistance
of bovine-origin S. Dublin isolates from 1986 through 2004 using a standard disk
diffusion method. High proportions of isolates throughout the time period were
resistant to one or more antimicrobials, and a marked increase in resistance to
ceftazidime occurred between 2000 and 2004. Dairy-origin isolates were more
likely to be resistant to several antibiotics than were isolates from beef
operations where exposure to antimicrobials is likely to be less frequent.
Plasmid analysis of a subset of isolates also supported the hypothesis that
antimicrobial resistance traits in the cattle-adapted serovar Dublin were
acquired within the bovine host environment.
PMID- 17034964
TI - Differentially expressed transcripts in shell glands from low and high egg
production strains of chickens using cDNA microarrays.
AB - We have constructed a tissue-specific in-house cDNA microarray to identify
differentially expressed transcripts in shell glands from low (B) and high (L2)
egg production strains of Taiwanese country chickens during their egg-laying
period. The shell gland cDNA library was constructed from the high egg production
strain. cDNA clones (7680) were randomly selected and their 5'-end sequences
characterized. After excluding overlapping sequences, an in-house cDNA
microarray, representing 2743 non-redundant transcripts, was generated for
functional genomic studies. Using our microarray, we have successfully identified
85 differentially expressed transcripts from the two different strains of chicken
shell glands. In this study, 34 of these transcripts were associated with signal
transduction, protein biosynthesis, cell adhesion, cellular metabolism, skeletal
development, cell organization and biogenesis. We selected a number of the
differentially expressed transcripts for further validation using semi
quantitative RT-PCR. These included elongation factor 2 (EEF2), ovocalyxin-32
(OCX-32) and annexin A2 (ANXA2) which were expressed at high levels in the
chicken shell glands of the B strain and, in contrast, the coactosin-like protein
(COTL1), transcription factor SOX18 and MX protein were more highly expressed in
the L2 strain. Our results suggest that these differentially expressed
transcripts may be suitable to use as molecular markers for high rates of egg
production, and now need to be investigated further to assess whether they can be
applied for use in breeding selection programs in Taiwanese country chickens.
PMID- 17034965
TI - Characterization of galactose-binding proteins in equine testis and spermatozoa.
AB - Carbohydrate-binding proteins are thought to be involved in a myriad of sperm
functions including sperm-oviductal and sperm-zona interactions. Recent studies
in our laboratory have characterized galactose-binding proteins on equine
spermatozoa as possible candidate molecules for sperm adhesion to oviduct
epithelial cells. In the current study, equine sperm membrane proteins were
subjected to galactose-affinity chromatography, and bound proteins were eluted
with excess galactose in a calcium-free buffer. The eluted fraction recovered
after galactose-affinity chromatography was used for generation of a polyclonal
antibody which was immobilized on an affinity column to recover a purified
protein from equine sperm extracts. Several protein bands of approximately 70,
25, and 20-18 kDa were detected with a major band at 25k Da on immunoblots which
was subjected to N-terminal amino acid sequencing. These galactose binding
proteins (GBP) were specific to sperm and testis and were absent in all the
somatic tissues tested. Based upon immunocytochemistry, GBP were localized over
the sperm head. In noncapacitated sperm, fluorescent labeling was observed over
the rostral sperm head as well as the postacrosomal area; whereas in capacitated
sperm, the labeling was localized primarily in the equatorial segment.
Immunohistochemistry of equine testis demonstrated abundant staining in the
adluminal region of the seminiferous tubules corresponding to round spermatids.
In summary, this study demonstrates the presence of testis- and sperm-specific
galactose binding proteins in the horse. The function of these proteins remains
to be determined.
PMID- 17034966
TI - Benefits and risks of long-term low-dose oral continuous combined hormone
therapy.
AB - OBJECTIVES: Current recommendations for hormone therapy (HT) are mainly based on
findings from studies using standard dose regimens in older women who had a
different health profile from those who start HT soon after the onset of
menopause. METHODS: We, therefore, reviewed controlled trials assessing the
efficacy, safety and tolerability of low-dose oral continuous combined HT (cc-HT)
started for treatment of climacteric symptoms. This review is limited to oral cc
HT regimens over sequential regimens as most postmenopausal women prefer not to
have a return of uterine bleeding, and to studies of at least 2 years in
duration. RESULTS: Low-dose cc-HT is effective in alleviating climacteric
symptoms and in maintaining bone density over prolonged periods, although no data
were available regarding fracture risk. No increased risk of coronary heart
disease, venous thrombo-embolism or stroke during the use of low-dose cc-HT was
reported in the long-term studies and no definitive evidence for an increased
risk of breast cancer was found. Breakthrough bleeding during the first months of
use is less common than with standard dose HT and amenorrhoea is achieved in most
women over time. These regimens are safe for the endometrium and are well
tolerated, with a low incidence of adverse events compared with standard doses.
CONCLUSIONS: Current evidence from controlled trials indicates that low-dose oral
cc-HT appears effective and safe. This makes it a good choice for the alleviation
of climacteric symptoms, and for this purpose long-term administration of low
dose cc-HT does not seem to impose serious health risks. However, more long-term
study data and direct head-to-head comparisons between various low-dose
preparations are needed to support or rectify the safety aspects.
PMID- 17034967
TI - Evaluation of the USP dissolution test method A for enteric-coated articles by
planar laser-induced fluorescence.
AB - The USP drug release standard for delayed-release articles method A was evaluated
using planar laser-induced fluorescence (PLIF). Prior authors have suggested that
high pH "hot spots" could develop during the buffer medium addition of the method
A enteric test. Additionally, previous studies have shown heterogeneous flow
patterns and low-shear regions in the USP Apparatus II dissolution vessel, which
may result in poor mixing of the buffer and acid media during the pH
neutralization step of the method A enteric test. In this study, PLIF was used to
evaluate the mixing patterns and evolution of pH neutralization during the buffer
medium addition with rhodamine-B dye and the pH-sensitive dye fluorescein,
respectively. Additionally, a comparison of the methods A and B enteric tests was
performed with enteric-coated tablets containing rhodamine-B in the film so as to
image the dissolution rate of the coating polymer with PLIF in order to determine
if rapid buffer addition for the method A procedure accelerates the rate of film
coat dissolution. Rapid addition of the 250 mL of buffer medium over 5 s to the
750 mL of acidic medium shows efficient mixing and pH neutralization due to the
generation of large-scale stirring and enhanced turbulence resulting from the
descending buffer medium. Slow addition near the paddle shaft over 5 min showed
segregation in the recirculating region around the paddle shaft. In contrast,
slow addition near the vessel wall introduces the medium into fluid outside of
the recirculation region and enables transport over the entire vessel. Enteric
coated tablets tested according to method A with rapid medium addition and method
B enteric tests performed identically, indicating no difference in polymer
dissolution rate between the two tests. From the results of the PLIF imaging
studies with rhodamine-B, fluorescein, and enteric-coated tablets, it was seen
that "hot spots" affecting the dissolution performance of enteric dosage forms
are not generated during the neutralization step of the method A enteric test
namely when the media is added rapidly or outside of the recirculating region
that surrounds the paddle shaft.
PMID- 17034968
TI - Bioavailability of riboflavin from a gastric retention formulation.
AB - A gastric retention formulation (GRF) made of naturally occurring carbohydrate
polymers and containing riboflavin was tested in vitro for swelling and
dissolution characteristics as well as in fasting dogs for gastric retention. The
bioavailability of riboflavin, a drug with a limited absorption site in the upper
small intestine, from the GRF was studied in fasted healthy humans and compared
to an immediate release formulation. It was found that when the GRF is dried and
immersed in gastric juice it swells rapidly and releases its drug content in a
zero-order fashion for a period of 24 h. In vivo studies in dogs showed that a
rectangular shaped GRF stayed in the stomach of fasted dogs for more than 9 h,
then disintegrated and reached the colon in 24 h. Endoscopic studies in dogs
showed that the GRF hydrates and swells back to about 75% of its original size in
30 min. These in vivo results correlated with in vitro results. Pharmacokinetic
parameters determined from urinary excretion data from six human subjects under
fasting conditions showed that bioavailability depended on the size of the GRF.
The biostudy indicated that bioavailability of riboflavin from a large size GRF
was more than triple that measured after administration of an immediate release
formulation. Deconvolved input functions from biostudy data suggest that the
large size GRF stayed in the stomach for about 15 h.
PMID- 17034970
TI - Wound healing activity of embelin isolated from the ethanol extract of leaves of
Embelia ribes Burm.
AB - Ethanol extract of the leaves of Embelia ribes Burm. (Myrsinaceae) and its
isolated quinone compound embelin were screened for wound healing activity by
excision, incision and dead space wound models on Swiss Albino Rats. Significant
wound healing activity was observed in both ethanol crude extract (30 mg/ml) and
the constituent treated groups. In embelin treated groups (4 mg/ml of 0.2% sodium
alginate gel), epithelialization of the incision wound was faster with a high
rate of wound contraction. The tensile strength of the incision wound was
significantly increased than the ethanol extract. In dead space wound model also
the weight of the granulation was increased indicating increase in collagenation.
The histological examination of the granulation tissue of embelin treated group
showed increased cross-linking of collagen fibers and absence of monocytes. The
wound healing effect was comparatively evaluated with the standard skin ointment
Framycetin.
PMID- 17034969
TI - Antimicrobial and anti-inflammatory activity of four known and one new
triterpenoid from Combretum imberbe (Combretaceae).
AB - Combretum imberbe is used widely in Africa inter alia for treating bacterial
infections. In addition to four known triterpenoids, 1alpha,3beta-dihydroxy-12
oleanen-29-oic (1), 1-hydroxy-12-olean-30-oic acid (2), 3,30-dihydroxyl-12
oleanen-22-one (3), and 1,3,24-trihydroxyl-12-olean-29-oic acid (4), a new
pentacyclic triterpenoid (1alpha,23-dihydroxy-12-oleanen-29-oic acid-3beta-O-2,4
di-acetyl-L-rhamnopyranoside) 5 has been isolated through a bioassay-guided
procedure from the leaves of Combretum imberbe. The structures of the compounds
were elucidated on the basis of 1D and 2D NMR experiments, as well as mass
spectrometric data. All compounds isolated had moderate (62 microg/ml) to strong
(16 microg/ml) antibacterial activity (MIC values) against Staphylococcus aureus
and Escherichia coli, with 1 and 5 being most active. Compounds 1 and 5 also
showed very strong inhibition of 3alpha-hydroxysteroid dehydrogenase with an
IC(50) of 0.3 microg/ml. Compound 5 indicated a moderate anti-proliferative
(GI(50)=16.5 and 13.2 microg/ml) and cytotoxic activity (CC(50)=17.6 micro/ml)
against K-562, L-929 and HeLa cell lines, respectively. The results of this study
give credence to the ethnomedicinal use of Combretum imberbe and expand our
knowledge on the biological activity of its metabolites.
PMID- 17034971
TI - Effects of Orthosiphon stamineus aqueous extract on plasma glucose concentration
and lipid profile in normal and streptozotocin-induced diabetic rats.
AB - The objective of this study was to investigate the effects of Orthosiphon
stamineus Benth. aqueous extract on plasma glucose concentration and lipid
profile in normal and streptozotocin-induced diabetic rats. The chemical
screening of the extract showed phenolic compound and flavonoid content were
13.24+/-0.33 mg/g and 1.73+/-0.14 microg/g, respectively. In oral glucose
tolerance test, the extract (0.2-1.0 g/kg) significantly decreased plasma glucose
concentration in a dose-dependent manner in both normal and diabetic rats. The
extract at 1.0 g/kg was most effective in decreasing plasma glucose
concentrations and the response was closed to the result of glibenclamide (5
mg/kg). After repeated daily oral administrations of the extract (0.5 g/kg) for
14 days, the extract significantly reduced plasma glucose concentration in
diabetic rats at days 7 and 14. By the end of the study, plasma triglyceride
concentration was lower in the extract-treated diabetic rats than untreated ones.
Furthermore, plasma HDL-cholesterol concentration was significantly increased in
diabetic rats treated with the extract. In perfused rat pancreas, the extract did
not increase insulin secretion in the presence of 5.5 mM glucose, but 100
microg/ml extract potentiated glucose-induced insulin secretion. Our findings
suggested that Orthosiphon stamineus aqueous extract is effective for alleviating
hyperglycemia and improving lipid profile in diabetic rats.
PMID- 17034973
TI - Identification of novel genes expressed in hypoxic brain condition by
fluorescence differential display.
AB - Fluorescence differential display (FDD) and comparative RT-PCR have been used
extensively to detect differentially expressed genes. We investigated hypoxia
induced gene expression in the brain by FDD-PCR and comparative RT-PCR. Mice were
anaesthetized after which hypoxia was induced by neck ligation for 1 min or 25
min, then were killed by decapitation, and the brains were dissected either
immediately or 30 min after death (Group A1-0, Group A25-0, Group A1-30 and Group
A25-30). Control mice without ligation of the neck were killed by decapitation
under anaesthesia immediately (Group C-0) or 30 min after death (Group C-30). FDD
PCR, sequence analysis and comparative RT-PCR revealed that mitochondrial
thymidine kinase 2, Rab6, selenoprotein T and two novel cDNAs were enhanced in
Group A25-0 and Group A25-30 compared with the other groups. In Group A25-30,
only RAP2 interacting protein and another novel cDNA were induced. In Group A25
0, one novel gene was detected. These findings were consistent with the results
of statistical analysis by ANOVA. No differences of band pattern were observed
among Groups A1-0, A1-30, C-0 and C-30. The genes exhibiting altered expression
were associated with vital cellular functions, e.g., intracellular signaling and
mitochondrial metabolism. In addition, we identified four novel genes, expressed
after extended hypoxic conditions in mouse brain with suffocation. These results
may contribute to clarify the pathophysiology of asphyxia in the brain and aid in
the diagnosis of suffocation.
PMID- 17034974
TI - Transient abducens nerve palsy during endoscopic sinus surgery: report of three
cases.
AB - Dysfunction of one or more of the ocular motor nerves or extraocular muscle
injury commonly results in diplopia. Diplopia during endoscopic sinus surgery is
caused by surgical trauma or local anesthetics. Transient abducens nerve palsy
rarely occurs after an intranasal sphenopalatine nerve block. We report three
cases of transient abducens nerve palsy during endoscopic sinus surgery and
possible explanations are proposed with a review of literature.
PMID- 17034975
TI - Initial experience with lung-MRI at 3.0T: Comparison with CT and clinical data in
the evaluation of interstitial lung disease activity.
AB - OBJECTIVES: We evaluated the feasibility of highfield lung-MRI at 3.0T. A
comparison with Computed Tomography (CT) and clinical data regarding the
assessment of inflammatory activity in patients with diffuse lung disease was
performed. MATERIAL AND METHODS: Prospective evaluation of 21 patients (15 males,
6 females, 43-80 y) with diffuse lung diseases who underwent clinical work-up
inclusive laboratory tests, lung-function tests and transbronchial biopsy. After
routine helical CT (additional 12 HRCT) a lung-MRI (3.0 Intera, Philips Medical
Systems, Best, The Netherlands) using a T2-weighted, cardiac and respiratory
triggered Fast-Spinecho-Sequence (TE/TR=80/1500-2500 ms, 22 transverse slices,
7/2mm slice-thickness/-gap) was performed. A pneumologist classified the cases
into two groups: A=temporary acute interstitial disease or chronic interstitial
lung disease with acute episode or superimposed infection/B=burned out
interstitial lung disease without activity. Two blinded CT-radiologists graded
the cases in active/inactive disease on the basis of nine morphological criteria
each. A third radiologist rated the MRI-cases as active/inactive, depending on
the signal-intensities of lung tissues. RESULTS: The pneumologist classified 14
patients into group A and 7 patients into group B. Using CT, 6 cases were
classified as active, 15 cases as inactive disease. With MRI 12 cases were
classified as active and 9 cases as inactive. In the complete group of 21
patients MRI decisions and CT decisions respectively were false positive/false
negative/correct in 2/4/15 respectively 0/8/13 cases. Correct diagnoses were
obtained in 72% (MRI) respectively 62% (CT). In the subgroup of 12 cases
including HRCT, MRI respectively CT were false positive/false negative/correct in
2/1/9 respectively 0/5/7 cases. Correct diagnoses were obtained in 75% (MRI)
respectively 58% (CT). CONCLUSION: Highfield MRI of the lung is feasible and
performed slightly better compared to CT in the determination of activity in
patients with interstitial lung diseases.
PMID- 17034976
TI - Determination of ganciclovir in different matrices from solid organ transplanted
patients treated with a wide range of concomitant drugs.
AB - The aim of the present study was to develop a time-efficient chromatographic
method for the analysis of therapeutic concentrations of ganciclovir (GCV) in
plasma, urine as well as dialysate (from continuous renal replacement therapy)
from solid organ transplant recipient treated with either GCV or its prodrug
valganciclovir (VGCV) in combination with a wide variety of other concomitant
drugs. Sample preparation was performed by reversed phase solid phase extraction
and was followed by separation of the analytes on a reversed phase column using
isocratic elution with a mobile phase consisting of acetonitrile-a counter ion
(50 mM 1-heptanesulfonic acid) in an aqueous sodium dihydrogen phosphate buffer
(pH 2.1; 10 mM) (10:90 v/v) and a fluorescence detector. Validation of the method
showed linearity within the concentration range of 0.1-40 microg/mL for plasma
and 0.1-120 microg/mL for urine and dialysate (R(2)>0.99, n> or =5). Accuracy and
precision (evaluated at 0.1, 5 and 40 microg/mL) were both satisfactory. The LLOQ
was determined to be 0.1 microg/mL. The method was successfully applied on
clinical samples from renal transplant recipients treated with VGCV in
combination with a variety of usually used concomitant drugs for solid organ
transplant recipients.
PMID- 17034977
TI - Rapid and simultaneous determination of sulfamethoxazole and trimethoprim in
human plasma by high-performance liquid chromatography.
AB - A simple and reproducible high-performance liquid chromatographic method was
developed for simultaneous determination of sulfamethoxazole (SMX) and
trimethoprim (TMP) in human plasma. The method entailed injection of the samples
after deproteination with perchloric acid and subsequent neutralizing. Primidone
was used as internal standard. Chromatography was performed on a C(18) column
(250 mm x 4.6 mm, 5 microm) under isocratic elution with 50 mM aqueous sodium
dihydrogen phosphate-acetonitrile-triethylamine (100:25:0.5, v/v), pH 5.9.
Detection was made at 240 nm and analyses were run at a flow-rate of 1.5 ml/min
at a temperature of 35 degrees C. The recovery was 83.4, 88.5 and 98.2% for TMP,
SMX and internal standard, respectively. The precision of the method was 2.6-9.8%
over the concentration range of 0.125-2 microg/ml for TMP and 0.39-50 microg/ml
for SMX. The limit of quantification (LOQ) in plasma was 0.125 and 0.39 microg/ml
for TMP and SMX, respectively. The method was used for a bioequivalence study.
PMID- 17034978
TI - Evaluation of an International Pharmacopoeia method for the analysis of
saquinavir (mesilate) bulk drugs by liquid chromatography.
AB - A single gradient LC method for the determination of related substances in both
saquinavir (SQV), saquinavir mesilate (SQVM) has been published in a consultation
document of the International Pharmacopoeia, WHO Drug Information. The method
uses a base deactivated reversed phase C18 column (25 cm x 4.6 mm i.d.), 5 microm
kept at a temperature of 30 degrees C. The mobile phases consist of acetonitrile,
methanol, phosphate buffer pH 3.4 and water. The flow rate is 1.0 ml/min. UV
detection is performed at 220 nm. A system suitability test (SST) is described to
govern the quality of the separation. The separation towards SQV(M) components
was investigated on 18 C18 columns and correlation was made with the column
classification system developed in our laboratory. The method was evaluated using
a Hypersil BDS C18 column (25 cm x 4.6 mm i.d.), 5 microm. A central composite
design was applied to examine the robustness of the method. The method shows good
precision, linearity, sensitivity and robustness. SQV(M) commercial samples of
bulk drugs were examined using this method.
PMID- 17034979
TI - Quantification of olanzapine polymorphs using powder X-ray diffraction technique.
AB - Accurate quantification of crystalline phases present in drug materials is
becoming increasingly important, due to stringent regulatory concerns about
polymorph characterization and control in drug substances and products. In the
present study, a quantification method for polymorphic forms of olanzapine (OLZ)
has been developed using powder X-ray diffraction (PXRD). Preferred orientation
has been reported to be the major source of error in PXRD analysis, therefore,
prior to development of a quantification method, pure polymorphic forms (I and
II) of different size ranges were analyzed. Preferred orientation effect was
found to decrease on using sieve fraction BSS # 120/240 for form I. In order to
obtain good peak resolution in optimum time, the step time and step size were
varied so as to optimize the scan rate. Among the five combinations selected,
step size of 0.05 degrees with step time of 5s demonstrated identification of
four characteristic peaks of form I in form II in 62 min. A calibration curve was
constructed in the range of 0-100% (w/w) using the characteristic peak of form I
at 18.48 degrees 2theta (I/I(0) 78.8%). The PXRD assay was reproducible and
precise and displayed a LOD of 0.40% (w/w) and LOQ of 1.22% (w/w). Validation
results showed excellent correlation between actual and predicted concentrations
with R(2) 0.9999.
PMID- 17034980
TI - Determination of kava lactones and flavonoid glycoside in Scorzonera austriaca by
capillary zone electrophoresis.
AB - A capillary zone electrophoretic method has been developed for the quantitative
analysis of three active comppounds, 12-hydroxy-desmethoxyyangonin (HD), 12-beta
d-glucopyranoside-desmethoxyyangonin (GD) and luteolin 3'-(6-E-p-coumaroyl-beta-d
glucopyranoside) (LG) in Scorzonera austriaca with UV detection at 254 nm. The
applied voltage was 25 kV and the capillary temperature was kept constant at 25
degrees C. The effect of buffer pH, the concentration of electrolyte and organic
modifier on migration were studied systematically. Optimum separation was
achieved with 20 mM borate buffer at pH 10.00 containing 10% (v/v) methanol.
Daphnetin was used as internal standard for quantification. Regression equations
revealed good linear relationship between the ratios of the peak area of each
compound and its the ratios of concentration. All the correlation coefficients
were higher than 0.9990. The relative standard deviations of migration time and
the peak area were <1.46% and 5.13% (inter-day), and <1.65% and 5.16% (intra
day), respectively. The contents of the three compounds in S. austriaca were
successfully determined with satisfactory repeatability and recovery.
PMID- 17034981
TI - Packed-bed bioreactors for mammalian cell culture: bioprocess and biomedical
applications.
AB - This article describes the development history of packed-bed bioreactors (PBRs)
used for the culture of mammalian cells. It further reviews the current
applications of PBRs and discusses the steps forward in the development of these
systems for bioprocess and biomedical applications. The latest generation of PBRs
used in bioprocess applications achieve very high cell densities (>10(8) cells
ml(-1)) leading to outstandingly high volumetric productivity. However, a major
bottleneck of such PBRs is their relatively small volume. The current maximal
volume appears to be in the range of 10 to 30 l. A scale-up of more than 10-fold
would be necessary for these PBRs to be used in production processes. In
biomedical applications, PBRs have proved themselves as compact bioartificial
organs, but their metabolic activity declines frequently within 1 to 2 weeks of
operation. A main challenge in this field is to develop cell lines that grow
consistently to high cell density in vitro and maintain a stable phenotype for a
minimum of 1 to 2 months. Achieving this will greatly enhance the usefulness of
PBR technology in clinical practice.
PMID- 17034982
TI - Age-dependent loss of insulin-like growth factor-1 receptor immunoreactive cells
in the supraoptic hypothalamus is reduced in calorically restricted mice.
AB - Both life-long caloric restriction (CR) and the suppression of insulin-like
growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The
neuroendocrine system, regulated by the hypothalamus, remains the most convincing
site of action for both these modes of life extension. Yet, determining whether
CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling
remains unclear. Of the hypothalamic nuclei that express the IGF-1 receptor (IGF
1R), the cells of the supraoptic nucleus (SON) display some of the most robust
IGF-1R expression. Taking IGF-1R immunoreactivity as an index of sensitivity to
IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the SON
of young-ad-libitum fed (young-Al, 6 weeks), old-ad-libitum fed (Old-Al, 22
months), and old-calorie-restricted (Old-CR, 22 months) female B6D2F1 mice. An
automated imaging microscopy system (AIMS) was used to generate cell counts for
each section of supraoptic hypothalamus. Results show that while the total number
of cells in the SON of ad-libitum fed mice does not change significantly with
aging, a significant reduction in IGF-1R immunoreactive cells does occur in ad
libitum fed mice with aging. In contrast to this, calorie restricted mice show
both a decline in the total number of cells and IGF-1R immunoreactive cells in
the SON with age, but with the decrease in the latter being notably attenuated
when compared to the degree of loss seen in ad-libitum fed mice. Thus, while CR
induces greater loss in the total number of cells in the SON with age, it reduces
the degree of age-dependent loss seen in IGF-1R expressing cells. As a result,
when compared to Old-AL mice, the SON of Old-CR mice displays a greater
proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with
aging.
PMID- 17034983
TI - Differential activities in adhesion and neurite growth of fibronectin type III
repeats in the PTP-delta extracellular domain.
AB - The full-length extracellular domain (ECD) of protein tyrosine phosphatase delta
(PTP-delta) functions as a ligand to promote cell adhesion and neurite outgrowth;
this ECD contains three immunoglobulin (Ig) repeats and eight fibronectin type
III (FN III) repeats. However, it is not known which regions of the ECD regulate
its ligand functions. Therefore, we constructed and expressed a fusion protein of
the PTP-delta ECD lacking FN III repeats 4-8, and tested this protein for
neuronal adhesion and neurite-promoting ability. Compared to the full-length
isoform, the truncated ECD was poorer at promoting adhesion, but a more potent
promoter of neurite growth. The results suggest that distal FN III repeats of PTP
delta are important in adhesive functions, but dispensable for neurite outgrowth
promotion. As the predominant isoform of PTP-delta during neural development
(type D) also lacks distal FN III repeats, the functional properties we observe
may be relevant to periods of axon extension, suggesting that splice variants of
receptor PTPs play distinct roles in neural development.
PMID- 17034984
TI - Intrastriatal hypoxanthine administration affects Na+,K+-ATPase,
acetylcholinesterase and catalase activities in striatum, hippocampus and
cerebral cortex of rats.
AB - The aim of this study was to investigate the effects of a single intrastriatal
injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan
disease, on Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities in
striatum, cerebral cortex and hippocampus of rats at different post-infusion
periods. Adult Wistar rats were divided in two groups: (1) vehicle-injected group
(control) and (2) hypoxanthine-injected group. For Na(+),K(+)-ATPase activity
determination, the animals were sacrificed 3h, 24h and 7 days after drug
infusion. For the evaluation of acetylcholinesterase and catalase activities, the
animals were sacrificed 30min, 3h, 24h and 7 days after hypoxanthine infusion.
Results show regional and time dependent effects of hypoxanthine on Na(+),K(+)
ATPase, acetylcholinesterase and catalase activities. The in vitro effect of
hypoxanthine on the same enzymes in striatum was also investigated. Results
showed that hypoxanthine inhibited Na(+),K(+)-ATPase, but not the activities of
acetylcholinesterase and catalase in rat striatum. We suggest that these
modification on cerebral biochemical parameters (Na(+),K(+)-ATPase,
acetylcholinesterase and catalase activities) induced by intrastriatal
administration of hypoxanthine in all cerebral structures studied, striatum,
hippocampus and cerebral cortex, could be involved in the pathophysiology of
Lesch-Nyhan disease.
PMID- 17034985
TI - Estrogen and androgen receptor expression in relation to steroid concentrations
in the adult boar epididymis.
AB - The steroid hormone regulation of the epididymis in a high estrogen producing
animal like the boar is not currently understood. To test the hypothesis that the
boar epididymis is an estrogen and androgen responsive tissue, the presence of
estrogen and androgen receptors, in conjunction with steroid hormone
concentrations were investigated in the boar epididymis. Epididymal (caput,
corpus, cauda) and testicular samples of boars (1-2.5 years; n=5) were collected
for immunolocalization of estrogen receptor alpha (ERalpha), estrogen receptor
beta (ERbeta) and androgen receptor (AR). Concentrations of testosterone,
estradiol and estrogen conjugates (EC) in the tissue were also determined. AR and
ERbeta were localized in the principal and basal cells of all three epididymal
regions. ERalpha was localized in the principal cells of the caput, some cells of
the corpus and was not present in the cauda. Testosterone (p<0.0001), estradiol
(p<0.0001) and EC (p<0.005) were significantly lower in the epididymis compared
with the testis. The epididymal regions were not significantly different from
each other for testosterone (p>0.15) or estradiol (p>0.09). EC were significantly
higher in the corpus than either the caput (p=0.003) or cauda (p=0.002). These
results suggest that the boar epididymis is responsive to both estrogens and
androgens and that both steroid hormones are important for proper epididymal
function. Since testosterone and estradiol concentrations are similar throughout
the epididymis, regional differences in steroid hormone regulation are likely due
to differences in receptor expression.
PMID- 17034986
TI - [Heparin-induced thrombocytopenia: report of four cases in severely burned
patients].
AB - Heparin-induced thrombocytopenia (HIT) is a dangerous complication of heparin
therapy caused by an antibody against heparin/Platelet Factor 4 (PF4) complex.
HIT complicates about 2% of treatment with unfractionated heparin (UFH). The aim
of the study was to determine the incidence of HIT in a burn center and to report
four cases in severely burned patients. HIT was documented in 2.8% of burns
treated with UFH administered for antithrombotic prophylaxis and in none of burns
receiving low molecular weight heparin (LMWH). All HIT cases occurred after
extensive deep burns (mean total body surface area or TBSA was 60+/-21%) and
three cases had above 75% of burn. We suggest that systemic platelet activation
after thermal injury and local production of PF4 in the burn wound could
participate to development of HIT. The risk is a late diagnosis since thrombosis
clinical detection under burned skin is difficult. HIT appears during the first
week of UHF treatment at the same time as a unstable period of fluctuating
platelets.
PMID- 17034987
TI - Maternal diabetes in vivo and high glucose concentration in vitro increases
apoptosis in rat embryos.
AB - Apoptosis may be involved in diabetes-induced embryonic dysmorphogenesis. We
estimated the occurrence of apoptosis in embryos of a rat model for diabetic
pregnancy. We found decreased Bcl-2, increased Bax and cleaved Caspase 3 proteins
in embryos from diabetic rats. Moreover, we found increased activation of Caspase
3 in cells from embryos previously exposed to a diabetes-like environment (in
vivo, in vitro) compared to cells from control embryos, which was normalized by
supplementation of N-acetylcysteine or apoptosis inhibitor. We detected increased
propidium iodide uptake in embryonic cells exposed to maternal diabetes, a
finding confirmed by vital staining. Additionally, we found increased
dysmorphogenesis in embryos exposed to a diabetic environment in vivo and in
vitro. Exposure to a diabetic milieu during organogenesis increases apoptosis in
embryonic cells and dysmorphogenesis in embryos. Enhanced apoptotic rate may have
a role in diabetic embryopathy by inducing disturbed embryonic maturation,
increased rates of resorptions and congenital malformations.
PMID- 17034988
TI - Glycine reduces cadmium-induced teratogenic damage in mice.
AB - The effect of glycine in preventing cadmium (Cd) teratogenicity in mice was
studied. Cadmium chloride (CdCl2) was administered subcutaneously at 1, 2 or 4
mg/kg doses on gestation days (GD) 7, 8 and 9. Glycine was given ad libitum (in
the drinking water) from GD0 through GD18 (the day when animals were killed), as
a 1% and 2% drinking water solution. Cd and nucleic acid concentrations in
embryos were determined. The most common finding seen after CdCl2 4 mg/kg
exposure was exencephaly. The incidence of this malformation was significantly
reduced in mice receiving 2% glycine while fetal Cd significantly decreased as
compared to cadmium-treated positive control animals. Increased nucleic acid
levels were seen in the same embryos. In glycine non-supplemented mice given
CdCl2 4 mg/kg, embryonic lipid peroxidation proved to be increased. In
conclusion, lipid peroxidation was associated with cadmium-induced
teratogenicity, and glycine inhibited the cadmium-induced effect by inhibiting
placental transport of cadmium. However, further detailed studies are needed to
establish the mechanism(s) of action.
PMID- 17034989
TI - Nonverbal social interaction skills of children with learning disabilities.
AB - Many children with learning disabilities (LD) face problems in their nonverbal
communication, which constitutes an important component of their social skills.
This study explores the frequency of nonverbal initiations and responses of 36
children with LD and 36 children without LD matched for age and gender, who were
observed for 40 min during the break. Younger and older children with and without
LD did not differ significantly in their nonverbal responses, but there was a
statistically significant difference in terms of younger children's nonverbal
initiations. Younger children with LD exhibited significantly fewer nonverbal
initiations than younger children without LD. Findings are discussed and
suggestions are made for further research.
PMID- 17034990
TI - Brief review of current research in FXS: implications for treatment with
psychotropic medication.
AB - The purpose of this paper is to provide a brief review of current research in
fragile X syndrome (FXS) with regards to the morphology and behavioral phenotype
associated with FXS and the use of psychotropic medication for the treatment of
behavior problems (e.g., aggression) often seen in FXS (full mutation). The lack
of production of the fragile X mental retardation protein (FMRP) is associated
with FXS and has been found to result in various neuronal changes such as altered
dendritic morphology and function as well as altered neurotransmitter functions.
A review of the basic literature on animal models and the relevance of these
findings for the use of psychotropic treatment of problem behaviors in FXS will
be discussed. Future research directions will be presented.
PMID- 17034991
TI - Robust rigid registration of retinal angiograms through optimization.
AB - Retinal fundus photographs are employed as standard diagnostic tools in
ophthalmology. Serial photographs of the flow of fluorescein and indocyanine
green (ICG) dye are used to determine the areas of the retinal lesions. For
objective measurements of features, the registration of the images is a
necessity. In this paper, we employ optimization techniques for registration with
the help of 2-parameter translational motion model of retinal angiograms, based
on non-linear pre-processing (Wiener filtering and morphological gradient) and
computation of the similarity criteria for the alignment of the two gradient
images for any given rigid transformation. The optimization methods are
effectively employed to minimize the similarity criterion. The presence of noise,
the variations in the background and the temporal variation of the fluorescence
level pose serious problems in obtaining a robust registration of the retinal
images. Moreover, local search strategies are not robust in the case of ICG
angiograms, even if one uses a multiresolution approach. The present work makes a
systematic comparison of different optimization techniques, namely the
minimization method derived from the optical flow formulation, the Nelder-Mead
local search and the HCIAC ant colony metaheuristic, each optimizing a similarity
criterion for the gradient images. The impact of the resolution and median
filtering of gradient image is studied and the robustness of the approaches is
tested through experimental studies, performed on macular fluorescein and ICG
angiographies. Our proposed optimization techniques have shown interesting
results especially for high resolution difficult registration problems. Moreover,
this approach seems promising for affine (6-parameter motion model) or elastical
registrations.
PMID- 17034992
TI - Penetration of moxifloxacin into sternal bone of patients undergoing routine
cardiopulmonary bypass surgery.
AB - This study investigated plasma and bone concentrations of moxifloxacin following
a single intravenous dose of 400mg to consider its potential role in the
treatment of osteomyelitis. Eight patients who underwent routine cardiopulmonary
bypass surgery were enrolled in the study. Plasma and bone samples were collected
2h and 5h after the end of infusion. High performance liquid chromatography was
used for the determination of moxifloxacin concentrations. Mean plasma
concentrations were 3.36 microg/mL and 2.93 microg/mL at 2h and 5h after the end
of infusion. The concentrations in the body and manubrium of the sternal bone
were 1.65 microg/g and 1.64 microg/g at 2h and 1.4 microg/g and 1.45 microg/g at
5h, respectively. Moxifloxacin showed good penetration into bone and could be
considered for the treatment of osteomyelitis.
PMID- 17034993
TI - Multi-azole resistance in Aspergillus fumigatus.
AB - Azole resistance in Aspergillus spp. is unusual. We report a patient who received
long-term treatment with itraconazole and voriconazole for bilateral chronic
cavitary aspergillosis with aspergillomas whose isolates of Aspergillus fumigatus
developed simultaneous resistance to itraconazole and voriconazole. A novel
mutation (G138C) in the target gene (cyp51A) encoding 14alpha-demethylase was
detected. The patient had some response to intravenous caspofungin, which he
received six times weekly, without the development of resistance over 9 months.
PMID- 17034994
TI - Stem cell based therapies to treat muscular dystrophy.
AB - Muscular dystrophies comprise a heterogeneous group of neuromuscular disorders,
characterized by progressive muscle wasting, for which no satisfactory treatment
exists. Multiple stem cell populations, both of adult or embryonic origin,
display myogenic potential and have been assayed for their ability to correct the
dystrophic phenotype. To date, many of these described methods have failed,
underlying the need to identify the mechanisms controlling myogenic potential,
homing of donor populations to the musculature, and avoidance of the immune
response. Recent results focus on the fresh isolation of satellite cells and the
use of multiple growth factors to promote mesangioblast migration, both of which
promote muscle regeneration. Throughout this chapter, various stem cell based
therapies will be introduced and evaluated based on their potential to treat
muscular dystrophy in an effective and efficient manner.
PMID- 17034995
TI - Xenopus cadherin-6 regulates growth and epithelial development of the retina.
AB - Cadherins are crucial for tissue cohesion, separation of cell layers and cell
migration during embryogenesis. To investigate the role of classical type II
Xcadherin-6 (Xcad-6), we performed loss-of-function studies by morpholino
oligonucleotide injections. This resulted in severe eye defects which could be
rescued with murine cadherin-6. In the absence of Xcadherin-6, morphological
alterations and a decrease in cell proliferation were observed with eye cup
formation. Eye field transplantations of Xcadherin-6 depleted donors yielded
grafts that failed to form a proper neuroepithelium in a wildtype environment. At
later developmental stages Xcadherin-6 deficient eyes showed lamination defects
in the outer neural retina, a reduced thickness of the ganglion cell layer (GCL)
and a fragmented retina pigment epithelium (RPE). Thus, Xcadherin-6 is essential
early in eye development for structural organization and growth of the
neuroepithelium before it differentiates into neural retina and RPE.
PMID- 17034996
TI - Conformational analysis of protein secondary structure during spray-drying of
antibody/mannitol formulations.
AB - Inhalation of spray-dried particles is a promising delivery route for proteins as
an alternative to injection. Changes in the protein structure and aggregation
have to be avoided. The effect of mannitol, a stabilizing agent typically used in
both liquid and lyophilized protein formulations, on an antibody (IgG1) in a
spray-dried powder was studied using different biophysical and chromatographic
techniques. At first, different solutions composed of antibody (IgG1) and
mannitol at a ratio between 20/80 and 100/0 IgG1/mannitol (100 mg/ml total solid)
were investigated for their stability. Protein solutions containing the IgG1
showed mannitol-dependent aggregation. High amounts of mannitol (50-80%) exerted
a destabilizing effect on the antibody and the aggregate 9 level increased to 2.6
4.2%. In contrast, solutions with only 20-40% mannitol showed the same amount of
aggregates as the pure antibody solution. The antibody mannitol solutions were
investigated by circular dichroism (CD) and Fourier transform infrared
spectroscopy (FTIR) to evaluate whether changes in the protein secondary
structure can be correlated with aggregation. Considering the sensitivity of the
used methods and data evaluation, FTIR spectra did not reveal structural changes
in the IgG1/mannitol solutions compared to the pure antibody, despite varying
aggregate levels. Thermal stress was reflected in perturbations of the secondary
structure, but mannitol-dependent aggregation could not be correlated to
detectable alterations in the FTIR spectra. Analyzing the CD spectra revealed no
distinctive change in the shape of the CD curve, indicating that the protein
secondary structure is mainly retained. This is in agreement with the infrared
data. Subsequently, the IgG1/mannitol solutions were spray-dried at Tin/Tout of
90/50 degrees C. Using ATR-FTIR for the investigation of the protein amide I band
in the spray-dried powder revealed changes in the sub-components of the amide I
band. This indicates that the peptide groups (CO and NH) of the protein are found
in a different environment in the solid state, compared to the liquid protein
formulation. After redissolution of the powders, the native structure of the pure
antibody solution was found identical to the protein secondary structure before
spray-drying, indicating that the protein secondary structure is not strongly
altered in the dry state, and not affected by the spray-drying process. Thus,
from the presented study it can be concluded that the formation of antibody
aggregates in mannitol formulations cannot be correlated with significant
perturbations of the protein secondary structure elements.
PMID- 17034997
TI - Matrix metalloproteinase inhibitor RO 28-2653 decreases liver metastasis by
reduction of MMP-2 and MMP-9 concentration in BOP-induced ductal pancreatic
cancer in Syrian Hamsters: inhibition of matrix metalloproteinases in pancreatic
cancer.
AB - BACKGROUND: Matrix metalloproteinases (MMP) are proteolytic enzymes which degrade
the extracellular matrix and therefore play an important role in metastasis.
However, the impact of MMP inhibitors (MMPI) on pancreatic cancer is still
unclear. Thus we evaluated the influence of selective MMPI Ro 28-2653 on the
incidence of liver metastases and the concentration of MMP-2 and MMP-9 in ductal
pancreatic adenocarcinoma in Syrian hamster. MATERIAL AND METHODS: One hundred
and thirty male Syrian hamsters were randomised into 8 groups (Gr.1-3: n=15, Gr.4
8: n=17). Pancreatic cancer was induced by weekly subcutaneous injection of 10mg
N-nitrosobis-2-oxopropylamin (BOP)/kg body weight (Gr.4-8) while healthy control
Gr. 1-3 received 0.5 ml sodium chloride 0.9%. Gr.1 and 4 had free access to a
standard diet, Gr. 2, 3 and 5-8 received a diet rich in polyunsaturated fatty
acids, which increases liver metastasis in this model. In week 17 oral therapy
started: Gr.3 and 6: 60 mg Eudragit/kg body weight/d (vehicle of MMPI), Gr.7 and
8: 40 mg, respectively, 120 mg RO 28-2653/kg body weight/d; Gr.1, 2, 4, 5: no
therapy. After 30 weeks all hamsters were sacrificed and histopathologically
examined. Additionally concentrations of MMP-2 and MMP-9 were measured in non
metastatic liver and liver metastases. RESULTS: Concentrations of MMP-2 and MMP-9
in liver metastases were decreased by high- and low-dose therapy with MMPI.
Furthermore, the incidence of liver metastases was significantly reduced by low
dose therapy with Ro 28-2653. CONCLUSION: Low-dose therapy with Ro 28-2653
decreased liver metastasis due to an inhibition of MMP-2 and MMP-9 concentration
in ductal pancreatic cancer.
PMID- 17034998
TI - Eosinophil cationic protein: is it useful in asthma? A systematic review.
AB - INTRODUCTION: Eosinophil cationic protein (ECP) has been widely investigated as a
potential biomarker of airway inflammation. METHOD: A systematic review was
performed using Medline with key terms eosinophil cationic protein and asthma,
limiting the search to titles or abstracts. Out of 688 potential papers found,
abstracts were reviewed based on the following criteria: (1) ECP was used as a
biological marker, (2) asthma was the index disease studied, (3) it was a
controlled clinical study and (4) ECP was assessed as a diagnostic, assessment or
management tool. One hundred and sixty-nine articles satisfied the selection
criteria and their full-text versions were reviewed. Only 53 papers were found to
provide clinically useful information. RESULTS: ECP has been measured in serum,
plasma, sputum, saliva and broncho-alveolar lavage fluids but serum and sputum
are the most established. Levels of ECP in normal and asthmatic subjects in
various body fluids were identified. ECP correlates well with airway inflammation
but not airway hyper-responsiveness. It is raised in other atopic diseases and
hence is not diagnostic for asthma. However, it has been shown to be useful in
assessing asthma severity, compliance with anti-inflammatory asthma therapy and
as a guide to tailing down inhaled corticosteroid therapy. Although there is some
evidence that ECP levels are affected by age, smoking, circadian rhythm and
seasonal variation, only smoking appears to be of clinical significance.
DISCUSSION: Despite its limitations, ECP remains potentially useful in asthma
management. Future research on ECP should focus on using serial measurements and
combining it with other markers of asthma which may increase its clinical
usefulness.
PMID- 17034999
TI - Transcription factors and hormones: new insights into plant cell differentiation.
AB - Plant development is a continuous process, mainly due to the presence of stem
cell niches within the root and shoot. The interplay between a host of
transcription factors determines whether the cells within the meristem maintain
their stem cell state, differentiate into leaves or form secondary meristems,
which develop into shoots and flowers. Several recent studies provide new insight
into how transcription factors and phytohormones interact within meristems to
control cell proliferation and differentiation.
PMID- 17035000
TI - A novel dry method for surface modification of SU-8 for immobilization of
biomolecules in Bio-MEMS.
AB - SU-8 has been primarily used for structural elements and microfludics components
in MEMS. Microsystems for biological applications require immobilization of
biomolecules on the MEMS structures. In order to functionalize SU-8 for such
purposes, the surface needs to be modified. In this paper, we report a novel dry
method of surface modification of SU-8 which is compatible with standard
microfabrication techniques. The surface obtained by spin coating SU-8 (2002) on
silicon wafer was modified by grafting amine groups using pyrolytic dissociation
of ammonia in a hotwire CVD setup. To demonstrate the presence of amine groups on
modified SU-8 surface, the surface characteristic after modification was assessed
using Fourier transform infrared spectroscopy. The change in SU-8 surface
morphology before and after surface modification was investigated using atomic
force microscopy. To show the utility of this process for application in Bio
MEMS, SU-8 microcantilevers were fabricated and subjected to the same surface
modification protocol. Following this, the cantilevers were incubated first in a
suspension of human immunoglobulin (HIgG) and then in FITC tagged goat anti-human
IgG in order to demonstrate the utility of the surface modification performed.
The efficacy of the process was assessed by observing the cantilevers under a
fluorescence microscope.
PMID- 17035001
TI - Transforming-growth factor beta1 Leu10Pro polymorphism and breast cancer
morbidity.
AB - TGF-beta1 has a dual role in carcinogenesis. In this gene, a leucine to proline
substitution in codon 10 leads to higher circulating levels of TGF-beta1. This
variant has been studied in relationship to the risk for breast cancer yielding
contradicting results. We aim to unravel the relationship of this polymorphism
and the risk of breast cancer. Women participating in the Rotterdam Study
including 143 patients with incident breast cancer were genotyped for this
polymorphism. We carried out a logistic regression and a survival analysis using
age as the time variable. The logistic regression analysis showed an increased
risk of breast cancer for Proline carriers (OR=1.4; 95% confidence interval
(CI)=1.1-2.0) versus non-carriers. The survival analysis showed that carriers of
the same allele had an increased risk of breast cancer (HR=1.4, 95% CI=1.1-2.0)
against non-carriers. Our data suggest that the TGF-beta1 Leu10Pro polymorphism
might play a role in breast cancer risk.
PMID- 17035002
TI - Retroperitoneal lymph node resection in patients with cervical cancer.
AB - OBJECTIVE: To determine predictive factors precluding complete resection of
metastatic lymph nodes identified by pre-operative imaging in patients with
cervical cancer. METHODS: Retrospective clinical review of patients with cervical
cancer with suspected metastases to pelvic and/or periaortic lymph nodes who
underwent lymph node dissection by laparotomy at The University of Texas M.D.
Anderson Cancer Center from September 1990-December 2004. RESULTS: A total of 104
patients were the subject of this analysis. Post-operatively, 25 patients (24%)
had negative lymph nodes, 62 patients (60%) had macroscopically positive lymph
nodes, one patient had microscopically positive (1%) and 16 patients (15%) had
unresectable lymph nodes. Body mass index did not have any impact on successful
resection of lymph nodes. On univariate analysis age (p=0.049) and size and
location of the largest lymph node were associated with resection status (p=0.001
and 0.020). Logistic regression confirmed that chance of achieving a successful
resection decreases with increasing age (p=0.046) and size of largest lymph node
(0.002). CONCLUSIONS: The ability to completely resect suspected metastatic lymph
nodes at the time of extraperitoneal lymph node dissection in patients with
cervical cancer is associated with size and location of largest lymph node.
PMID- 17035003
TI - Decolorization and partial degradation of monoazo dyes in sequential fixed-film
anaerobic batch reactor (SFABR).
AB - Decolorization of two monoazo dyes, acid orange 6 (AO6) and acid orange 7 (AO7),
were studied in sequential fixed-film anaerobic batch reactor (SFABR) with
varying dye concentrations and 500 mg/L glucose as the co-substrate. More than
90% dye decolorization could be achieved, even at 300 mg/L, with both AO6 and AO7
and dye decolorization rates were 168 mg/L/d and 176 mg/L/d, respectively. COD
removals with these two monoazo dyes were significantly different, as 75% and 35%
decrease were observed with AO6 and AO7, respectively. UV-visible spectral as
well as HPLC analysis of SFABR treated effluent showed the accumulation of 4
aminobenzenesulfonate (4-ABS) from AO6 and AO7. Aminoresorcinol (AR) formed from
AO6 decolorization could not be detected at the end of SFABR cycle. This along
with high COD removal indicated its further degradation. Formation of pink
coloration on exposure to air indicated the presence of 1-amino-2-naphthol (AN)
in AO7 fed reactor effluent. Thus both 4-ABS and AN were resistant to further
degradation under anaerobic conditions. Presence of nitrate did not decrease the
observed decolorization at the end of 24h SFABR cycle, although initial rate was
decreased. This indicates the suitability of SFABR configuration for the
treatment of azo-dye containing wastewaters in the presence of nitrate.
PMID- 17035004
TI - Enhanced productivity of Chaetoceros calcitrans in airlift photobioreactors.
AB - The various modes of cultivation of Chaetoceros calcitrans in airlift
photobioreactors (ALPBRs) were examined. The batch system illustrated that the
airlift configuration was superior to the bubble column as the airlift supported
the circulation of the cell within the system, leading to a better light
utilization. The cultivations in both semi-continuous and continuous systems
resulted in a high cell productivity, although the steady state cell
concentrations in both systems were lower than that obtained from the batch
system. The behavior of the large-scale airlift system was not significantly
different from the conventional bubble column where the diatom could only be
produced at low cell density. Despite this, among all of the systems investigated
in this work, the large-scale system gave the highest productivity. The main
limiting factor for the large-scale airlift culture was the availability of
light. Based on economical analysis, the continuous cultivation in the 2.8L ALPBR
with a medium feed rate of 3 mL min(-1) was most attractive where the operation
cost could be maintained at a minimum of approx. 7.95 x 10(-4)THBL(-1)h(-1).
However, this continuous small-scale system still suffered from relatively low
cell productivity (8.10 x 10(4)cellss(-1)).
PMID- 17035005
TI - Efficiency of Penicillium chrysogenum PTCC 5037 in reducing low concentration of
chromium hexavalent in a chromium electroplating plant wastewater.
AB - The effectiveness of Penicillium chrysogenum was evaluated for reducing Cr(VI)
from the wastewater of a chromium electroplating plant. Statistically-based
experimental designs were applied to optimize the condition for reducing Cr(VI)
to Cr(III). By applying Plackett-Burman factorial design and central composite
design as the optimization step, attempts were made to identify optimal values of
the three factors that bringing about maximum microorganism activity and
therefore maximum hexavalent chromium(VI) bioreduction. It was found that each
gram of P. chrysogenum of dry biomass condition could reduce 66 mg of Cr(VI) to
Cr(III) in the wastewater of the chromium electroplating plant.
PMID- 17035006
TI - The implication of Dichomitus squalens laccase isoenzymes in dye decolorization
by immobilized fungal cultures.
AB - The study focuses on the production of ligninolytic enzymes and dye degradation
capacity of Dichomitus squalens immobilized on polyurethane foam (PUF) or pine
wood (PW) in a fixed bed reactor at a laboratory scale (working volume of 0.6l).
Immobilization of fungal cultures on pine wood improved eminently laccase
production in comparison to the liquid cultures. Immobilized D. squalens was able
to decolorize an anthraquinone dye Remazol Brilliant Blue R and an azo dye
Reactive Orange 16, however, only a limited decolorization of
Copper(II)phthalocyanine dye was observed in both types of reactor cultures. The
involvement of a laccase activity in dye decolorization was suggested. Further,
two different chromatographical forms of laccases, Lc1 and Lc2, were isolated
from PW cultures of D. squalens using a fast, two step FPLC method. Enzymes
revealed identical molecular masses of 68 kDa (estimated by SDS-PAGE) and similar
pI's, however, they differed in their catalytic properties such as pH dependence
of the activity and ABTS oxidation rates. In this study, we demonstrated
different dye decolorization capacities of Lc1 and Lc2 as well.
PMID- 17035007
TI - DNA sequence recognition in the minor groove by hairpin microgonotropens.
AB - Two novel microgonotropens (MGTs) comprised of hairpin N-propylaminepyrrole
polyamides linked to a Hoechst 33258 (Ht) analogue (3 and 4) were synthesized on
solid phase by adopting an Fmoc technique using a series of HOBt mediated
coupling reactions. The dsDNA-binding properties of MGTs 3 and 4 were determined
by thermal denaturation experiments. Both MGTs were found to be selective for
their nine-bp match dsDNA sequence 9 and were less tolerant of G/C bp
substitutions in the binding region than linear progenitor MGT 1. MGT 3 was
intolerant of a G/C substitution located in the middle of the binding region and
did not bind to sequences 13 and 14. MGT 4 also did not bind to sequence 13, and
its linker-bound Ht moiety was found to be more sensitive to a G/C substitution
in the Ht-binding target, as demonstrated by the lack of binding to sequence 16.
PMID- 17035008
TI - Synthesis of bisdesmosidic kryptogenyl saponins using the 'random glycosylation'
strategy and evaluation of their antitumor activity.
AB - A bisdesmosidic steroidal saponins library, composed of 16 novel kryptogenin
glycosides, was set up via six random glycosylation procedures, wherein two
compounds showed their antitumor activity against HeLa cell in the preliminary
pharmacological research.
PMID- 17035010
TI - N-Substituted carbazolyloxyacetic acids modulate Alzheimer associated gamma
secretase.
AB - N-Sulfonylated and N-alkylated carbazolyloxyacetic acids were investigated for
the inhibition and modulation of the Alzheimer's disease associated gamma
secretase. The introduction of a lipophilic substituent, which may vary from
arylsulfone to alkyl, turned 2-carbazolyloxyacetic acids into potent gamma
secretase modulators. This resulted in the selective reduction of Abeta(42) and
an increase of the less aggregatory Abeta(38) fragment by several compounds
(e.g., 7d and 8c). Introduction of an electron donating group at position 6 and 8
of N-substituted carbazolyloxyacetic acids either decreased the activity or
inversed modulation. The most active compounds displayed activity on amyloid
precursor protein (APP) overexpressing cell lines in the low micromolar range and
little or no effect on the gamma-secretase cleavage at the epsilon-site.
PMID- 17035009
TI - Identification of a series of highly potent activators of the Nurr1 signaling
pathway.
AB - The nuclear receptor Nurr1 (NR4A2) is critically involved in the development and
maintenance of midbrain dopaminergic neurons and is believed to function
independently of endogenous activation. The hit identification and SAR studies
leading to isoxazolo-pyridinone 7e, a highly potent, brain penetrable activator
of the Nurr1 signaling pathway, are described.
PMID- 17035011
TI - Screening of alpha-helical peptide ligands controlling a calcineurin-phosphatase
activity.
AB - In this paper, we describe an application of 202-membered fluorescently labeled
peptide library designed to take an alpha-helix secondary structure. As a proof
of-concept experiment, a calmodulin (CaM)/calcineurin (Cn) pair was chosen to
screen alpha-helical peptide ligands that tightly bind to CaM and also control
enzymatic functions of Cn. Three peptides were successfully selected from the
library by assaying Cn-phosphatase activities and peptide-CaM interactions (dual
check process). The strategy using a designed peptide library shows real promise
as a peptide-based high-throughput screening system.
PMID- 17035012
TI - ATP-conjugated peptide inhibitors for calmodulin-dependent protein kinase II.
AB - Substrate analog peptides of CaMKII with varying degrees of the inhibitory
potency were linked to ATPgammaS either by considering a phosphoryl transfer
mechanism or simply by using a relatively long flexible linker. The latter
bisubstrate inhibitors showed relatively little effects while the former ones
improved inhibitory potency to different levels depending on the binding
affinities of the peptide moieties. One of the mechanism-based bisubstrate
inhibitors was then utilized to demonstrate an ATP-competitive but peptide
substrate-uncompetitive inhibition, supporting an ordered binding mechanism for
CaMKII.
PMID- 17035013
TI - Halogenation of 4-hydroxy-3-methoxybenzyl thiourea TRPV1 agonists showed enhanced
antagonism to capsaicin.
AB - Selected potent TRPV1 agonists (1-6) have been modified by 5- or 6-halogenation
on the aromatic A-region to analyze their effects on potency and efficacy
(agonism versus antagonism). The halogenation caused enhanced functional
antagonism at TRPV1 compared to the corresponding prototype agonists. The
analysis of SAR indicated that the antagonism was enhanced as the size of the
halogen increased (I>Br>Cl) and when the 6-position was halogenated. Compounds
23c and 31b were found to be potent full antagonists with K(i) (as functional
antagonist)=23.1 and 30.3 nM in rTRPV1/CHO system, respectively.
PMID- 17035014
TI - Intelligent fluorescent nucleoside in sensing cytosine base: importance of
hydrophobic nature of perylene fluorophore.
AB - Fluorescence response upon hybridization of perylene labeled oligonucleotide
probes depends on the microenvironment experienced by the perylene fluorophore.
In mismatched duplex ((Per)U-C), enhanced fluorescence was observed while in
matched duplex ((Per)U-A) fluorescence intensity decreased considerably. This
observation will be a promising research effort in giving rise to a new powerful
tool in detection of SNP.
PMID- 17035015
TI - Syntheses of F-18 labeled fluoroalkyltyrosine derivatives and their biological
evaluation in rat bearing 9L tumor.
AB - We hereby report the synthesis of four fluorine-18 labeled tyrosine derivatives,
3-(2-[(18)F]fluoroethyl)tyrosine ([(18)F]1, [(18)F]ortho-FET), 3-(3
[(18)F]fluoropropyl)tyrosine ([(18)F]2, [(18)F]ortho-FPT) O-methyl-[3-(2
[(18)F]fluoroethyl)]tyrosine ([(18)F]3, [(18)F]MFET), and O-methyl-[3-(3
[(18)F]fluoropropyl)]tyrosine ([(18)F]4, [(18)F]MFPT). The fluorine-18 labeled
tyrosine derivatives were prepared by the displacement reaction of the ethyl and
propyl tosylates with K[(18)F]/K2.2.2 in acetonitrile under no-carrier-added
(NCA) conditions, followed by hydrolysis with 4N HCl. The biological properties
of labeled compounds were evaluated in rats bearing 9L tumor after an intravenous
injection and PET image was obtained. The tumor/blood and tumor/brain ratios were
2.06, 2.92 for [(18)F]1, 2.25, 4.05 for [(18)F]2, 2.88, 1.90 for [(18)F]3, and
2.00, 2.60 for [(18)F]4 at 60 min post injection, respectively. The PET image
showed localized accumulation of PET tracers in 9L glioma of the rat.
PMID- 17035016
TI - Glucose-specific poly(allylamine) hydrogels--a reassessment.
AB - Polymer hydrogels synthesized by crosslinking poly(allylamine hydrochloride) with
(+/-)-epichlorohydrin in the presence of d-glucose-6-phosphate monobarium salt do
not show imprinting on the molecular level. A series of hydrogels was prepared
using the following five templates: d-glucose-6-phosphate monobarium salt, d
glucose, l-glucose, barium hydrogen phosphate (BaHPO(4)), and d-gluconamide; a
hydrogel was also prepared in the absence of a template. For all six hydrogels,
batch binding studies were conducted with d-glucose, l-glucose, d-fructose, and d
gluconamide. The extent of analyte sugar binding was determined using (1)H NMR.
Each hydrogel shows approximately the same relative binding affinity for the
different sugar derivatives, and none displays selectivity for either glucose
enantiomer. The results of the binding studies correlate with the octanol-water
partition coefficients of the sugars, indicative that differential solubilities
in the bulk polymer account for the binding affinities observed. Thus, in
contrast to templated hydrogels prepared using methacrylate- or acrylamide-based
reagents, true imprinting does not occur in this novel, crosslinked
poly(allylamine hydrochloride) system.
PMID- 17035017
TI - 2,6-Quinolinyl derivatives as potent VLA-4 antagonists.
AB - A new series of 2,6-quinolinyl derivatives was prepared leading to potent low
nanomolar VLA-4/VCAM-1 antagonists.
PMID- 17035018
TI - Identification of novel, selective and potent Chk2 inhibitors.
AB - A series of isothiazole carboxamidine compounds were synthesized and discovered
as novel and selective inhibitors for Chk2. They are not active against the
related Chk1 kinase. The structure-activity relationship studies were performed
on the scaffold, and enzymatic kinetic analysis showed they are simple ATP
competitive inhibitors with K(i) values as low as 11 nM for Chk2. Computer
modeling studies were employed to comprehend the mechanism of action and SAR of
these compounds.
PMID- 17035019
TI - 4-Aminopyrimidines as novel HIV-1 inhibitors.
AB - A series of 4-aminopyrimidines (1) was identified as novel HIV inhibitors of
unknown molecular target. Structural modifications were carried out to establish
its SAR and identify the linking site for target identification. A number of
analogs were found to possess single digit inhibitory activity for HIV
replication. Several analogs with various potential linkers, including a
biotinated analog, also exhibited excellent potency, and could serve as tools for
the identification of novel anti-HIV targets.
PMID- 17035020
TI - Actin' together: serum response factor, its cofactors and the link to signal
transduction.
AB - The vast diversity of cellular types and behaviours is mainly the result of
combinatorial interactions between a limited number of transcription factors and
cellular signalling pathways whose activity is stringently controlled by
developmental, cellular and extracellular cues. Studies of serum response factor
(SRF) have provided a paradigm for such interactions for some years. Recent
advances have shown that two families of SRF cofactors, the ternary complex
factors (TCFs) and the myocardin-related transcription factors (MTRFs), are
regulated by separate signalling pathways and thereby control SRF target genes
differentially. The actin cytoskeleton is both an upstream regulator of MRTF
activity, with monomeric actin directly acting as a signal transducer, and a
downstream effector, because of the many cytoskeletal target genes. Here we
discuss how the competition among cofactors might integrate these distinct
signalling pathways into a specific transcriptional response and biological
function.
PMID- 17035022
TI - A method to standardize gait and balance variables for gait velocity.
AB - Many gait and balance variables depend on gait velocity, which seriously hinders
the interpretation of gait and balance data derived from walks at different
velocities. However, as far as we know there is no widely accepted method to
correct for effects of gait velocity on other gait and balance measures. We
developed a simple statistical method to obtain gait and balance variables for
each participant that are independent of gait velocity. The first step of our
standardization method was the transformation of the gait and balance data to
obtain a normal distribution and decrease the influence of outliers. Thereafter,
we constructed a formula, based on regression analysis that described how these
data varied with gait velocity in each participant during walking without an
additional task. Last, this formula was used to standardize the gait and balance
data for the effect of gait velocity for each individual participant. As example
we present the analysis of mediolateral displacements of the trunk in fit elderly
people during walking with and without a dual task.
PMID- 17035021
TI - Effect of Tai Chi on gait and obstacle crossing behaviors in middle-aged adults.
AB - This study investigated whether long-term, habitual practice of Tai Chi (or
Taiji) results in behavioral modifications during gait. Specifically, we examined
whether Tai Chi (TC) experience alters gait behavior during normal and obstructed
walking. Fifteen experienced TC practitioners and fifteen control subjects
(average age 45 years, 23-66 year range) completed level walking trials with or
without a stationary obstacle placed in their path. TC practitioners in this
study had an average of 6.5 years (1.5-15 year range) of Chen-style Tai Chi
experience. Kinematic analyses performed on their step-to-step gait
characteristics over multiple steps revealed that TC practitioners used a more
cautious strategy by using slower gait speeds and shorter and slower steps than
controls (p 100 microM); that is, exhibited >51-fold
greater selectivity for TRH-R2 versus TRH-R1. Analog 8, in which pGlu is replaced
with pAad and histidine is substituted at the N-1(tau) position with a methyl
group, exhibited a binding affinity (K(i)=0.0032 microM) to TRH-R1 that is
similar to that of [Ntau(1)-Me-His]-TRH and displayed potent activation of TRH-R1
and TRH-R2 (EC(50)=0.0049 and 0.0024 microM, respectively). None of the analogs
in which pGlu is replaced with the bioisosteric (R)- and (S)-(Ocp) and the
imidazole ring is substituted at the N-1(tau) or C-2 position were found to bind
or activate either TRH-R1 or TRH-R2 at the highest test dose of 100 microM.
PMID- 17035025
TI - Synthesis of 6-chloroisoquinoline-5,8-diones and pyrido[3,4-b]phenazine-5,12
diones and evaluation of their cytotoxicity and DNA topoisomerase II inhibitory
activity.
AB - The substituted chloroisoquinolinediones and pyrido[3,4-b]phenazinediones were
synthesized, and the cytotoxic activity and topoisomerase II inhibitory activity
of the prepared compounds were evaluated. Chloroisoquinolinediones have been
prepared by the reported method employing 6,7-dichloroisoquinoline-5,8-dione. The
cyclization to pyrido[3,4-b]phenazinediones was achieved by adding the aqueous
sodium azide solution to the dimethylformamide solution of corresponding
chloroisoquinoline-5,8-dione. The cytotoxicity of the synthesized compounds was
evaluated by a SRB (Sulforhodamine B) assay against various cancer cell lines
such as A549 (human lung cancer cell line), SNU-638 (human stomach cancer cell),
Col2 (human colon cancer cell line), HT1080 (human fibrosarcoma cell line), and
HL-60 (human leukemia cell line). Almost all the synthesized pyrido[3,4
b]phenazinediones showed greater cytotoxic potential than ellipticine
(IC(50)=1.82-5.97 microM). In general, the cytotoxicity of the pyrido[3,4
b]phenazinediones was higher than that of the corresponding
chloroisoquinolinediones. The caco-2 cell permeability of selected compounds was
0.62 x 10(-6)-35.3 x 10(-6)cm/s. The difference in cytotoxic activity among
tested compounds was correlated with the difference in permeability to some
degree. To further investigate the cytotoxic mechanism, the topoisomerase II
inhibitory activity of the synthesized compounds was estimated by a plasmid
cleavage assay. Most of compounds showed the topoisomerase II inhibitory activity
(28-100%) at 200 microM. IC(50) values for the most active compound 6a were 0.082
microM. However, the compounds were inactive for DNA relaxation by topoisomerase
I at 200 microM.
PMID- 17035024
TI - Synthesis and evaluation of antitumor activity of novel N-acyllavendamycin
analogues and quinoline-5,8-diones.
AB - A series of 7-N-acyllavendamycins with zero, one or two substituents at the C-2',
C-3', and C-11' were synthesized through short and efficient methods. Pictet
Spengler condensation of 7-N-acylamino-2-formylquinoline-5,8-diones with
tryptamine or tryptophans produced the desired lavendamycins. Screening data on a
panel of three ras oncogene-transformed cell lines and the non-transformed parent
cell line showed that a significant number of these analogues are potent
antitumor agents and appear to be particularly active against K-ras transformed
cells. Compared with the corresponding quinolinediones, these novel lavendamycins
are much more inhibitory toward the transformed cells indicating that the beta
carboline moiety of the lavendamycin analogues plays an important role in its
potency and selective toxicity.
PMID- 17035027
TI - Apoptosis induction and modulation of P-glycoprotein mediated multidrug
resistance by new macrocyclic lathyrane-type diterpenoids.
AB - The macrocyclic lathyrane diterpenes, latilagascenes D-F (1-3) and jolkinol B
(4), were isolated from the methanol extract of Euphorbia lagascae, and evaluated
for multidrug resistance reversing activity on mouse lymphoma cells. All
compounds displayed very strong activity compared with that of the positive
control, verapamil. The structure-activity relationship is discussed. The
evaluation of compounds 1 and 4, and of latigascenes A-C (5-7), isolated from the
same species, as apoptosis-inducers was also carried out. Compound 1 was the most
active. Furthermore, in the model of combination chemotherapy, the interaction
between the doxorubicine and latilagascene B (6) was studied in vitro, on human
MDR1 gene transfected mouse lymphoma cells, showing that the type of interaction
was synergistic. Latilagascenes D-F (1-3) are new compounds whose structures were
established on the basis of spectroscopic methods, including 2D NMR experiments
(COSY, HMQC, HMBC and NOESY).
PMID- 17035028
TI - Structure of C-terminal fragment of merozoite surface protein-1 from Plasmodium
vivax determined by homology modeling and molecular dynamics refinement.
AB - One current vaccine candidate against Plasmodium vivax targeting asexual blood
stage is the major merozoite surface protein-1 of P. vivax (PvMSP-1). Vaccine
trials with PvMSP-1(19) and PvMSP-1(33) have succeeded in protecting monkeys and
a large proportion of individuals, naturally exposed to P. vivax transmission,
develop specific antibodies to PvMSP-1(19). This study presents a model for the
three-dimensional structure of the C-terminal 19kDa fragment of P. vivax MSP-1
determined by means of homology modeling and molecular dynamics refinement. The
structure proved to be consistent with MSP-1(19) of known crystal or solution
structures. The presence of a main binding pocket, well suited for protein
protein interactions, was determined by CASTp. Corrections reported to the
sequence of PvMSP-1(19) Belem strain were also inspected. Our model is currently
used as a basis to understand antibody interactions with PvMSP-1(19).
PMID- 17035029
TI - Synthesis and biophysical evaluation of minor-groove binding C-terminus modified
pyrrole and imidazole triamide analogs of distamycin.
AB - Five polyamide derivatives with rationally modified C-terminus moieties were
synthesized and their DNA binding specificity and affinity determined. A
convergent approach was employed to synthesize polyamides containing an
alkylaminopiperazine (4 and 5), a truncated piperazine (6), or an alkyldiamino-C
terminus moiety (7 and 8) with two specific objectives: to investigate the
effects of number of potential cationic centers and steric bulk at the C
terminus. CD studies confirmed that compounds 4, 5, 7, and 8 bind in the minor
groove of DNA. The alkylpiperazine containing compounds (4 and 5) showed only
moderate binding to DNA with DeltaT(m) values of 2.8 and 8.3 degrees C with their
cognate sequence, respectively. The alkyldiamino compounds (7 and 8) were more
impressive producing a DeltaT(m) of >17 and >22 degrees C, respectively. Compound
6 (truncated piperazine) did not stabilize its cognate DNA sequence. Footprints
were observed for all compounds (except compound 6) with their cognate DNA
sequence using DNase I footprinting, with compound 7 producing a footprint of 0.1
microM at the expected 5'-ACGCGT-3' site. SPR analysis of compound 7 binding to
5'-ACGCGT-3', 5'-ACCGGT-3', and 5'-AAATTT-3' produced binding affinities of
2.2x10(6), 3.3x10(5), and 1x10(5)M(-1), respectively, indicating a preference for
its cognate sequence of 5'-ACGCGT-3'. These results are in good agreement with
the footprinting data. The results indicate that steric crowding at the C
terminus is important with respect to binding. However, the number of cationic
centers within the molecule may also play a role. The alkyldiamino-containing
compounds (7 and 8) warrant further investigation in the field of polyamide
research.
PMID- 17035030
TI - Structural advantage of dendritic poly(L-lysine) for gene delivery into cells.
AB - This study aimed to investigate the relationships between structures of gene
carrier molecules and their activities for gene delivery into cells. We compared
2 types of poly(L-lysine) as carriers, that is, dendritic poly(L-lysine) (KG6)
and linear poly(L-lysine) (PLL). KG6 formed a neutral DNA complex, and its DNA
compaction level was weaker than that of PLL. The amount of DNA binding and
uptake into cells mediated by PLL was 4-fold higher than that with KG6. However,
KG6-mediated gene expression was 100-fold higher than that by PLL. Since pK(a)
values of terminal amines of KG6 were lowered even though small amounts of DNA
were internalized into cells, sufficient DNA amounts for effective gene
expression escaped to the cytosol due to the proton sponge effect in the
endosome. In addition, weakly compacted DNA with KG6 was advantageous in
accessing RNA polymerase in the cell nucleus. On the other hand, PLL did not show
the proton sponge effect in the endosome and resulted in strong compaction of
DNA. Even though large DNA amounts were internalized into cells, most of the DNA
would not take part in gene expression systems in the nucleus. Amount of induced
cytokine production after intravenous injection of DNA complexes with KG6 and PLL
was low, and was similar to the case when DNA was injected alone. Therefore, no
significant difference in effects on cytokine production was observed between KG6
and PLL.
PMID- 17035031
TI - Role of glutamate 243 in the active site of 2-deoxy-scyllo-inosose synthase from
Bacillus circulans.
AB - 2-Deoxy-scyllo-inosose (DOI) synthase is involved in the biosynthesis of 2
deoxystreptamine-containing aminoglycoside antibiotics and catalyzes the
carbocyclic formation from d-glucose-6-phosphate (G-6-P) into DOI. The reaction
mechanism is proposed to be similar to that of dehydroquinate (DHQ) synthase in
the shikimate pathway, and includes oxidation of C-4, beta-elimination of
phosphate, reduction of C-4, ring opening, and intramolecular aldol cyclization.
To investigate the reaction mechanism of DOI synthase, site-directed mutational
analysis of three presumable catalytically important amino acids of DOI synthase
derived from the butirosin producer Bacillus circulans (BtrC) was carried out.
Steady state and pre-steady state kinetic analysis suggested that E243 of BtrC is
catalytically involved in the phosphate elimination step. Further analysis of the
mutant E243Q of BtrC using substrate analogue, glucose-6-phosphonate, clearly
confirmed that E243 was responsible to abstract a proton at C-5 in G-6-P and set
off phosphate elimination. This glutamate residue is completely conserved in all
DOI synthases identified so far and the corresponding amino acid of DHQ synthase
is completely conserved as asparagine. Therefore, this characteristic glutamate
residue of DOI synthase is a key determinant to distinguish the reaction
mechanism between DOI synthase and DHQ synthase as well as primary sequence.
PMID- 17035032
TI - Synthesis and characterization of styrylchromone derivatives as beta-amyloid
imaging agents.
AB - Several promising agents have been synthesized and evaluated for in vivo imaging
probes of beta-amyloid plaques in Alzheimer's disease (AD) brain. Recently, we
have developed flavone derivatives, which possess the basic structure of the 2
phenylchromone, as useful candidates for amyloid imaging agents. In an attempt to
further develop novel tracers, we synthesized and evaluated a series of 2
styrylchromone derivatives, which replace the 2-phenyl substituent of flavone
backbone with the 2-styryl. A series of radioiodinated styrylchromone derivatives
were designed and synthesized. The binding affinities for amyloid plaques were
assessed by in vitro binding assay using pre-formed synthetic Abeta(1-40)
aggregates. The new series of styrylchromone derivatives showed high binding
affinity to Abeta aggregates at the K(d) values of 32.0, 17.5 and 8.7nM for
[(125)I]6, [(125)I]9, and [(125)I]12, respectively. In biodistribution studies
using normal mice, [(125)I]6 and [(125)I]9 examined in normal mice displayed high
brain uptakes with 4.9 and 2.8%ID/g at 2min post injection. The radioactivity
washed out from the brain rapidly (1.6 and 1.0%ID/g at 60min post injection for
[(125)I]6 and [(125)I]9, respectively). But [(125)I]12 did not show marked brain
uptake, and the washout rate from the brain was relatively slow throughout the
time course (1.1 and 1.4%ID/g at 2 and 30min post injection, respectively).
Although additional modifications are necessary to improve the brain uptake and
rapid clearance of non-specifically bound radiotracer, the styrylchromone
backbone may be useful as a backbone structure to develop novel beta-amyloid
imaging agents.
PMID- 17035033
TI - Novel T-type calcium channel blockers: dioxoquinazoline carboxamide derivatives.
AB - T-type calcium channel is one of therapeutic targets for the treatment of
cardiovascular diseases and neuropathic pains. Since the withdrawal of
mibefradil, a T-type calcium channel blocker, there have been a lot of efforts to
develop T-type calcium channel blockers. A small molecule library of
dioxoquinazoline carboxamide derivatives containing 155 compounds was designed,
synthesized, and biologically evaluated for T-type calcium channel blocking
activity. Among those compounds synthesized, the compound 1n shows the most
potent T-type calcium current blocking activity with an IC(50) value of 1.52
microM, which is comparable to that of mibefradil.
PMID- 17035034
TI - Synthesis and biological evaluation of dihydrofuran-fused perhydrophenanthrenes
as a new anti-influenza agent having novel structural characteristic.
AB - Dihydrofuran-fused perhydrophenanthrenes were synthesized by means of o
quinodimethane chemistry with high generality and stereoselectivity, and found to
exhibit potent anti-influenza activity. These compounds exerted an inhibitory
effect on various strains of influenza virus growth, including influenza A and B,
with a concentration dependent manner, and direct cytotoxicity was low. Several
biological experiments suggested that these new drugs affected a virus
replication process before mRNA synthesis stage. Novel rigid cage-type of
structural characteristic of the compounds has not been found in hitherto anti
influenza drugs, and will provide new basis and motif for exploring promising and
unprecedented anti-influenza agents.
PMID- 17035035
TI - Green route for the heterocyclization of 2-mercaptobenzimidazole into beta-lactum
segment derivatives containing -CONH- bridge with benzimidazole: Screening in
vitro antimicrobial activity with various microorganisms.
AB - The efficient and rapid synthesis of novel azetidin-2-ones 4a-j has been
established. Thus, both microwave and conventional condensation 2-{(1H
benzimidazol)-ylthio}-N'-2-(substituted phenyl) hydrazide with
chloroacetylchloride were carried out in DMF-benzene solvent in the presence of
Et(3)N catalyst. The microwave synthesis route afforded better yield with short
time. The novel heterocycles were characterized by elemental analysis and
spectral features. Some of the produced compounds were screened for their
antimicrobial activity.
PMID- 17035037
TI - Synthesis of diverse analogues of Oenostacin and their antibacterial activities.
AB - Several diverse analogues of Oenostacin, a naturally occurring potent
antibacterial phenolic acid derivative, have been synthesized. A small library
with more than forty analogues having different aromatic rings and varied side
chains has been achieved through solution phase synthesis. Some of these
analogues, that is, 22, 23 and 42, possessed potent antibacterial activities
against Staphylococcus epidermidis and Staphylococcus aureus having EC(50)
ranging from 0.49 to 0.67 microM as compared to Oenostacin (EC(50)=0.12 microM).
PMID- 17035036
TI - Discovery of diphenyl amine based sodium channel blockers, effective against
hNav1.2.
AB - The development of new therapies for chronic pain is an area of unmet medical
need. Central to pathways of chronic pain is the upregulation of voltage-gated
sodium channels. The use of tricyclic antidepressants, which also have sodium
channel activity, in chronic pain therapy prompted us to develop novel compounds
from this scaffold. Herein, we show that the tricyclic moiety is not needed for
effective inhibition of the [(3)H]-BTX binding site and sodium currents of
hNa(v)1.2. Our lead compound 6, containing a diphenyl amine motif, demonstrated a
53% inhibitory block of Na(v)1.2 currents at 10microM, which is greater than 50%
increase in current block in comparison to the amitriptyline standard. Altogether
our study establishes that the tricyclic motif is unnecessary for hNa(v)1.2
activity and modification of the amine portion is detrimental to sodium channel
block.
PMID- 17035038
TI - Tri-, tetra- and heptacyclic perylene analogues as new potential antineoplastic
agents based on DNA telomerase inhibition.
AB - A recent approach in anticancer chemotherapy envisages telomerase as a
potentially useful target. An attractive strategy deals with the development of
compounds able to stabilize telomeric DNA in the G-quadruplex folded structure
and, among them, a prominent position is found in the perylenes. With the aim to
further investigate the role of drug structure, in view of possible
pharmaceutical applications, we synthesized a series of compounds related to
PIPER, a well-known perylene-based telomerase inhibitor. We modified the number
of condensed aromatic rings and introduced different side chains to modulate drug
protonation state and extent of self-aggregation. Effective telomerase inhibition
was induced by heptacyclic analogues only, some showing a remarkably wide
selectivity index with reference to inhibition of Taq polymerase. G-quadruplex
stabilization was monitored by circular dichroism and melting experiments. Cell
cytotoxicity measurements indicated a poor short-term cell killing ability for
the best G-quartet binders. Besides the presence of a planar seven-condensed ring
system, the introduction of a cyclic amine in the side chains critically affects
the selectivity window.
PMID- 17035039
TI - Morphological findings and energy dispersive X-ray microanalysis of oral amalgam
tattoos.
AB - Oral amalgam tattoos (AT) are distinct pigmentations of the oral mucosa resulting
from accidental incorporation of dental amalgam in the oral soft tissues. Dental
amalgams and in particular mercury, one of the constituents of dental amalgams,
have for long been considered toxic. Oral ATs are easily accessible to study soft
tissue reaction to amalgam and its degradation products. In this study, 17 oral
ATs were examined by transmission electron microscopy and energy dispersive X-ray
microanalysis. Ultrastructurally, in the ATs, three kinds of electron-dense
particles were observed. The largest particles ranged in size from 0.5 up to
several 100 microm. Smaller electron-dense inclusions (0.5-0.1 microm) were seen
extracellularly associated with meshworks of elastic fibers and collagen bundles.
The third and smallest type of particles (5-30 nm in diameter) was found with
basement membranes of small vessels and pericytes and particularly decorating
collagen bundles. Element analysis regularly revealed the presence of silver,
sulphur, copper and lead in the AT decay products. Mercury was found in only one
instance. Tissue reactions due to ATs seem to be minimal. No acute inflammatory
changes were seen. Larger inclusions occasionally were surrounded by macrophages
and multinucleated cells. TEM and element analysis may in specific cases be
helpful in the differential diagnosis of pigmented lesions of the oral mucosa.
PMID- 17035040
TI - A new digital autoradiographical method for identification of Pu particles using
an imaging plate.
AB - An autoradiographical method using an imaging plate (IP) was developed to
identify rapidly the density of plutonium (Pu) particles on filter samples.
Photostimulated luminescence (PSL) signals were obtained by exposing IPs to
filter samples collecting Pu particles and naturally occurring radon decay
products, respectively. Search and analysis of the alpha-induced PSL signals
presented the time-dependent growth of PSL intensity from the Pu particles and
the range of PSL intensities from radon decay products, making it possible to
discriminate Pu particles from radon decay products using an empirical Pu
discrimination level, and then to quantify the Pu activities on a particle-by
particle basis. The method is useful for a fast screening of filter samples for
Pu particles because it requires no special skills and tedious procedures during
its use, gives a low discriminable activity for individual Pu particles with a
relatively short exposure time, and allows us to measure a large number of filter
samples at the same time.
PMID- 17035041
TI - NANC inhibitory neuromuscular transmission in the hamster distal colon.
AB - The neurotransmitter(s) that generate the inhibitory junctional potential (IJP)
in the circular muscle of hamster distal colon and their mechanisms have not been
elucidated. The aim of the present study, therefore, was to determine the
contributing roles of the non-adrenergic, non-cholinergic (NANC) inhibitory
transmitter(s) including nitric oxide (NO), adenosine 5'-triphosphate (ATP) and
vasoactive intestinal polypeptide (VIP) in the generation of IJP in the hamster
distal colon. For this purpose, the effects of the corresponding blockers of
these putative NANC inhibitory mediators have been investigated using
microelectrode technique. Intracellular membrane potential recordings were made
from smooth muscle cells at 35 degrees C in Tyrode's solution that contained
atropine (0.5microM), guanethidine (3microM) and nifedipine (0.5microM). Single
electrical stimuli (0.5ms, 50V) as well as trains of two and five pulses (20Hz at
the same duration and voltage) elicited NANC IJP consisted of initial fast (IJP
F) followed by a slow hyperpolarization (IJP-S). The response had been abolished
by tetrodotoxin (TTX, 0.3microM). The nitric oxide synthase (NOS) inhibitor, N(G)
nitro-L-arginine methyl ester (L-NAME; 200microM) blocked IJP-S but enhanced IJP
F. The later had been blocked with suramin, a universal P2 receptor antagonist,
or with CBF3GA, a P2Y receptor antagonist at dose-dependent fashions. The IJP-F
had been markedly inhibited by desensitization of P2Y receptor with its putative
agonist 2-methylthio-ATP (2-meSATP, 50microM for 30min). IJP-F was sensitive to
the P2Y1 receptor specific antagonist A3P5PS (10microM) and to the G-protein
inhibitor, pertussis toxin (PTX, 400ng/ml for 2h) as well as to the small and
intermediate Ca(2+) sensitive K(+) channels blocker, apamin (0.3microM). IJP-S
was blocked by the guanylate cyclase (GC) inhibitor, 1H-[1,2,4]oxadiazolo-[4,3
a]quinoxalin-1-one (ODQ, 10microM) and was partially sensitive to apamin.
Exogenously applied ATP (100microM-1mM) produced typical hyperpolarization that
was blocked by suramin, CBF3GA and 2-meSATP desensitization; while exogenously
applied NO (3-10microM) produced slowly developing hyperpolarization that was not
blocked by L-NAME but ODQ. In the presence of both purinergic and nitrergic
inhibitors, stimulation using a train of eight pulses at 25Hz evoked a small slow
hyperpolarization that was sensitive to the VIP antagonist (VIP 6-28, 1microM).
Exogenous application of VIP (1-10microM) produced similar response that was not
evident in the presence of VIP 6-28. These data indicate that NANC IJP that is
generated in the circular muscle cells of hamster distal colon is mediated by ATP
and NO via P2Y1/P2Y2 receptor and GC-dependent pathways, respectively. A masked
role for VIP is also indicated.
PMID- 17035042
TI - What immunologists should know about bacterial communities of the human bowel.
AB - The human bowel is home to a bacterial community of much complexity. This article
summarizes current bacteriological knowledge of the community and highlights
topics of potential interest to innovative immunologists. The role of the
bacterial community in the development and regulation of the immune system of
neonates seems likely to be a particularly important area of future research.
PMID- 17035043
TI - Induced expression of Olig2 is sufficient for oligodendrocyte specification but
not for motoneuron specification and astrocyte repression.
AB - To dissect out interactions between the transcription factor Olig2 and other
intrinsic and extrinsic factors in neural cell fate determination, we established
a mouse embryonic stem (ES) cell line with induced expression of Olig2 along
neural differentiation. During neuronal differentiation, both the control and
Olig2-induced groups produced a similar proportion of HB9-expressing motoneurons
in the presence of retinoic acid (RA) and sonic hedgehog (SHH), but both
generated few motoneurons in the absence of SHH. Induced Olig2 expression did not
alter the pattern of gene transcription without SHH, suggesting that Olig2
requires cooperation with RA and SHH for motoneuron specification. During glial
differentiation, the Olig2-induced group generated significantly more
oligodendrocytes and fewer neurons and astrocytes than the control group. This
effect was not blocked by inhibition of SHH signaling, suggesting that Olig2
bypasses the need of SHH in oligodendrocyte specification. However, treatment
with ciliary neurotropic factor (CNTF) markedly increased astrocyte and decreased
oligodendrocyte differentiation even when Olig2 is sustained in the nuclei,
suggesting that Olig2 cannot bypass the CNTF-STAT signaling to repress astrocyte
differentiation.
PMID- 17035044
TI - Measuring pad-pad pinch strength in a non-human primate: Macaca fascicularis.
AB - The primary purpose of this study was to establish a methodology for determining
and perhaps predicting (via regression analysis of anthropometric measures)
Macaca fascicularis isometric pinch strength for a specific task. The larger
purpose of this work was to properly scale a pinching task for the monkeys in
order to study dose-response relationships in a non-human primate model for
carpal tunnel syndrome. Three female and one male macaque (n=4) of varying size
and age were trained to perform a left-handed pad-pad pinch. The task required 60
degrees of wrist flexion at a static pinching distance of 3 cm between the thumb
and fingers. Subjects were trained for a period of 20-weeks. After that time, an
analysis of performance gradients found that they had each reached a plateau in
their force output. Pinch strength for the four animals ranged from 29.4 to 59.8
N. Regression analysis revealed that body mass (kg) and wrist circumference (cm)
were both predictive of pinch strength, exhibiting adjusted R(2) values of 0.93
(p=0.024) and 0.96 (p=0.015), respectively. Thus, the results suggest that
maximal pinch strength could be acceptably estimated in future subjects using
either the wrist circumference or the body mass measures, as both were strong
predictors of pad-pad pinch strength.
PMID- 17035045
TI - EEG/(f)MRI measurements at 7 Tesla using a new EEG cap ("InkCap").
AB - We aimed at improving the signal-to-noise ratio (SNR) of electroencephalography
(EEG) during magnetic resonance imaging (MRI) by introducing a new EEG cap
("InkCap") based on conductive ink technology. The InkCap was tested with
temperature measurements on an electrically conductive phantom head and during
structural and functional MRI (fMRI) recordings in 11 healthy human volunteers at
7 T. Combined EEG/fMRI measurements were conducted to study the interaction
between the two modalities. The EEG recordings with the InkCap demonstrated up to
a five-fold average decrease in signal variance during echo-planar imaging, with
respect to a cap made of standard carbon fiber leads. During concurrent EEG/fMRI
measurements in human volunteers, alpha oscillations were clearly detected at 7
T. Minimal artifacts were present in the T2* and high-resolution structural MR
images of the brain parenchyma. Our results show that the InkCap technology
considerably improves the quality of both EEG and (f)MRI during concurrent
measurements even at 7 T.
PMID- 17035046
TI - Implicit learning deficits in dyslexic adults: an fMRI study.
AB - It is assumed that several neuropsychological impairments characterize the
cognitive profile of individuals with developmental dyslexia (DD). Phonological
and visual processing are often impaired as well as auditory processing,
attention, and information processing speed. Although reports in the literature
on implicit learning abilities are contradictory, recent neurological and
physiological data suggest that these abilities are deficient in individuals with
DD. To evaluate implicit learning we administered a classical version of the
serial reaction time task (SRTT) related to sequence learning. Using functional
magnetic resonance imaging we investigated brain activation patterns associated
with implicit learning deficits in 14 adults with DD matched with 14 normal
readers. SRTT results indicated the absence of implicit learning in the DD group
and different activations between groups mainly in SMA, inferior parietal areas
and cerebellar lobule 6. These results can be interpreted in the light of the
different capacities for the two groups to build an internal model to guide
movements. Further, they explain DD individuals' difficulty in domains not
directly related to reading ability.
PMID- 17035047
TI - Human brain glucose metabolism may evolve during activation: findings from a
modified FDG PET paradigm.
AB - In human brain, short-term physiological stimulation results in dramatic and
proportional increase in blood flow and metabolic rate of glucose but minimal
change in oxygen utilization, however, with continuing stimulation, we have
observed that blood flow response diminishes and oxygen utilization increases.
Given the temporal limitation of conventional methods to measure glucose
metabolism in the human brain, we modified [(18)F]fluorodeoxyglucose (FDG) PET
paradigm to evaluate the short-term and long-term effects of visual stimulation
on human brain glucose metabolism. In the present study, seven healthy volunteers
each underwent three dynamic FDG PET studies: at rest and after 1 min and 15 min
of visual stimulation (using reversing black-white checkerboard) which continued
for only 5 min after FDG injection. We found that increase in FDG uptake in the
visual cortex was attenuated by 28% when preceded by 15 min of continuous visual
stimulation (p<0.001). This decline in metabolism occurred in the absence of any
behavior changes in task performance. The similarity in behavior of blood flow
and glucose metabolism over time supports the hypothesis that, in activated
brain, blood flow is modulated by changes in cytosolic free NADH/NAD(+) ratio
related to increased glycolysis. Furthermore, the observed decline in glucose
metabolism may reflect a shift from glycolytic to oxidative glucose metabolism
with continued activation.
PMID- 17035048
TI - Quantitative mapping of basal and vasareactive cerebral blood flow using split
dose 123I-iodoamphetamine and single photon emission computed tomography.
AB - A new method has been developed for diffusible tracers, to quantify CBF at rest
and after pharmacological stress from a single session of dynamic scans with dual
bolus administration of a radiotracer. The calculation process consisted of three
steps, including the procedures of incorporating background radioactivity
contaminated from the previous scan. Feasibility of this approach was tested on
clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart,
were carried out on each subject, after each of two split-dose administrations of
111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the
second IMP injection. Additional PET scans were also carried out on 6 subjects on
a separate day, at rest and after acetazolamide administration. The other 5
subjects were scanned only at rest during the whole study period. Quantitative
CBF obtained by this method was in a good agreement with those determined with
PET (y(ml/100 g/min)=1.07x(ml/100 g/min)-1.14, r=0.94). Vasareactivity was
approximately 40% over the whole cerebral area on healthy controls, which was
consistent with a literature value. Reproducibility of CBF determined in the rest
rest study was 1.5+/-5.7%. Noise enhancement of CBF images, particularly the
second CBF, was reduced, providing reasonable image quality. Repeat assessment of
quantitative CBF from a single session of scans with split-dose IMP is accurate,
and may be applied to clinical research for assessing vascular reactivity in
patients with chronic cerebral vascular disease.
PMID- 17035050
TI - Effect of sodium valproate monotherapy on serum uric acid concentrations in
ambulatory epileptic children: a prospective long-term study.
AB - PURPOSE: Hyperuricemia has been shown to be related to cardiovascular morbidity
and mortality. There is controversial data about the effect of sodium valproate
(VPA) monotherapy on serum uric acid concentrations. The purpose of this study
was to investigate by a long-term, prospective method, whether treatment with VPA
monotherapy may alter serum uric acid concentrations and liver function tests in
ambulatory epileptic children. MATERIAL AND METHODS: Serum uric acid
concentrations were determined in 28 ambulatory epileptic children before and at
6, 12 and 24 months of VPA monotherapy. Serum concentrations of biochemical
markers of liver and renal function, such as alanine aminotransferase (ALT),
aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma
glutamyltransferase (gamma-GT) and creatinine (Cr) were also measured before and
at 6, 12 and 24 months of VPA monotherapy. Serum VPA concentrations remained
within the therapeutic range (50-100 mg/L) during the period of study. RESULTS:
No statistically significant changes in serum uric acid concentrations were found
at 6, 12 or 24 months of treatment. Serum ALT concentrations were significantly
increased at 6 and 12 months of treatment, AST concentrations at 6 and 12 months
of treatment and LDH concentrations at 12 months of treatment. CONCLUSIONS: VPA
monotherapy does not have a significant effect on serum uric acid concentrations
in ambulatory epileptic children. Further studies are needed to definitively
address whether it would be useful for physicians to routinely check for elevated
serum uric acid levels in children treated with VPA.
PMID- 17035049
TI - 3D pattern of brain atrophy in HIV/AIDS visualized using tensor-based
morphometry.
AB - 35% of HIV-infected patients have cognitive impairment, but the profile of HIV
induced brain damage is still not well understood. Here we used tensor-based
morphometry (TBM) to visualize brain deficits and clinical/anatomical
correlations in HIV/AIDS. To perform TBM, we developed a new MRI-based analysis
technique that uses fluid image warping, and a new alpha-entropy-based
information-theoretic measure of image correspondence, called the Jensen-Renyi
divergence (JRD). METHODS: 3D T1-weighted brain MRIs of 26 AIDS patients (CDC
stage C and/or 3 without HIV-associated dementia; 47.2+/-9.8 years; 25M/1F; CD4+
T-cell count: 299.5+/-175.7/microl; log10 plasma viral load: 2.57+/- 1.28 RNA
copies/ml) and 14 HIV-seronegative controls (37.6+/-12.2 years; 8M/6F) were
fluidly registered by applying forces throughout each deforming image to maximize
the JRD between it and a target image (from a control subject). The 3D fluid
registration was regularized using the linearized Cauchy-Navier operator. Fine
scale volumetric differences between diagnostic groups were mapped. Regions were
identified where brain atrophy correlated with clinical measures. RESULTS: Severe
atrophy ( approximately 15-20% deficit) was detected bilaterally in the primary
and association sensorimotor areas. Atrophy of these regions, particularly in the
white matter, correlated with cognitive impairment (P = 0.033) and CD4+ T
lymphocyte depletion (P = 0.005). CONCLUSION: TBM facilitates 3D visualization of
AIDS neuropathology in living patients scanned with MRI. Severe atrophy in
frontoparietal and striatal areas may underlie early cognitive dysfunction in
AIDS patients, and may signal the imminent onset of AIDS dementia complex.
PMID- 17035051
TI - Severe neurological complications in skeletal dysplasias: two case reports.
AB - Skeletal dysplasias form a diverse and genetically heterogeneous group of
disorders, but also share many clinical and radiographic features. We describe
two illustrative cases and provide a short review of the literature on the
neurological complications associated with various groups of skeletal dysplasias.
These two cases illustrate that management of skeletal dysplasias requires a
multidisciplinary approach, aimed at preventing or minimizing medical
complications. Follow-up should include regular comprehensive neurological
evaluation, as neurological complications can be severe and are often treatable
if diagnosed at an early stage.
PMID- 17035052
TI - Neuronal ceroid lipofuscinoses (NCL).
PMID- 17035054
TI - Discovery of new potent human protein tyrosine phosphatase inhibitors via
pharmacophore and QSAR analysis followed by in silico screening.
AB - A pharmacophoric model was developed for human protein tyrosine phosphatase 1B (h
PTP 1B) inhibitors utilizing the HipHop-REFINE module of CATALYST software.
Subsequently, genetic algorithm and multiple linear regression analysis were
employed to select an optimal combination of physicochemical descriptors and
pharmacophore hypothesis that yield consistent QSAR equation of good predictive
potential (r = 0.87,F-statistic = 69.13,r(BS)2 = 0.76,r(LOO)2 = 0.68). The
validity of the QSAR equation and the associated pharmacophoric hypothesis was
experimentally established by the identification of five new h-PTP 1B inhibitors
retrieved from the National Cancer Institute (NCI) database.
PMID- 17035053
TI - Anterior encephalocele associated with subependymal nodular heterotopia, cortical
dysplasia and epilepsy: case report and review of the literature.
AB - The presence of subependymal nodular heterotopia and cortical dysgenesis has been
infrequently reported in patients with encephalocele. The majority of these
patients were found to have posterior encephaloceles. We report a case of a
Hispanic female with a frontoethmoidal encephalocele who developed epilepsy at 15
years of age. Magnetic resonance imaging of the brain demonstrated left
subependymal nodular heterotopia, partial agenesis of the corpus callosum and
left fronto-temporal cortical dysplasia with polymicrogyria. This case
illustrates the association of anterior encephalocele with subependymal nodular
heterotopia, cortical dysplasia and epilepsy. It underscores the importance of
screening for intracranial abnormalities in patients with anterior encephalocele.
PMID- 17035055
TI - The molecular dynamics of assembly of the ubiquitous aortic medial amyloidal
medin fragment.
AB - In recent years there is an increased understanding of the molecular conformation
of amyloid fibrils. However, much less is known about the early events that lead
to the formation of these medically important assemblies. The clarification of
these very important mechanistic details on the process may indicate directions
towards the inhibition of the early stages of the assembly, where harmful species
are most likely to form. Here, we study the dynamics of assembly of short
amyloidogenic peptide fragments from the medin polypeptide. This polypeptide is
of unique interest since amyloid deposits composed of medin are found almost in
all the population above the age of 50. Twelve independent 50 ns long molecular
dynamics simulations in explicit water have been run on peptide NH2-NFGSVQFV
COOH, the minimal recognition hexapeptide element, NH2-NFGSVQ-COOH, and several
single-point mutants. In all cases a three-stranded polymeric beta-sheet was used
as the basic unit from which fibrils can be formed. Our results clearly indicate
the need of well-defined sequence and stereochemical constraints to allow the
formation of stable well-ordered aggregates. One of the key findings is the need
for the presence of a phenylalanine residue, but not other hydrophobic amino
acids, in specific positions within the peptide. Taken together, the results are
consistent with recent high-resolution structures of amyloid assemblies and
provide unique insights into the dynamics of these structures.
PMID- 17035056
TI - Resveratrol alleviates bleomycin-induced lung injury in rats.
AB - Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant
balance such as pulmonary fibrosis. This study was designed to examine the
effects of resveratrol, an antioxidant agents, against bleomycin-induced
pulmonary fibrosis and oxidative damage. Wistar albino rats were administered a
single dose of bleomycin (5 mg/kg; via the tracheal cannula) followed by either
saline or resveratrol (10 mg/kg; orally) for 14 days. The effect of resveratrol
on pulmonary oxidative damage was studied by cell count and analysis of cytokine
levels (TGF-beta, TNF-alpha, IL-1beta and IL-6) in the bronchoalveolar lavage
fluid (BALF) and biochemical measurements of malondialdehyde (MDA), an end
product of lipid peroxidation; glutathione (GSH), a key antioxidant; and
myeloperoxidase (MPO) activity, an index of neutrophil infiltration, in the lung
tissue. Bleomycin-induced lung fibrosis was determined by lung collagen contents
and also microscopically. Bleomycin caused a significant decrease in lung GSH,
which was accompanied with significant increases in MDA level, MPO activity, and
collagen contents of the lung tissue concomitant with increased levels of the pro
inflammatory mediators and cell count in BALF. On the other hand, resveratrol
treatment reversed all these biochemical indices as well as histopathological
alterations induced by bleomycin. The results demonstrate the role of oxidative
mechanisms in bleomycin-induced pulmonary fibrosis, and resveratrol, by its
antioxidant properties, ameliorates oxidative injury and fibrosis due to
bleomycin. Thus, an effective supplement with resveratrol as an adjuvant therapy
may be a very promising agent in alleviating the side effects of bleomycin, an
effective chemotherapeutic agent.
PMID- 17035057
TI - Anoxia tolerance in turtles: metabolic regulation and gene expression.
AB - Freshwater turtles of the Trachemys and Chrysemys genera are champion facultative
anaerobes able to survive for several months without oxygen during winter
hibernation in cold water. They have been widely used as models to identify and
understand the molecular mechanisms of natural anoxia tolerance and the molecular
basis of the hypoxic/ischemic injuries that occur in oxygen-sensitive systems and
underlie medical problems such as heart attack and stroke. Peter L. Lutz spent
much of his career investigating turtle anaerobiosis with a particular focus on
the mechanisms of brain ion homeostasis and neurotransmitter responses to anoxia
exposure and the mechanisms that suppress brain ion channel function and neuronal
excitability during anaerobiosis. Our interests intersected over the mechanisms
of metabolic rate depression which is key to long term anoxia survival. Studies
in my lab have shown that a key mechanism of metabolic arrest is reversible
protein phosphorylation which provides coordinated suppression of the rates of
multiple ATP-producing, ATP-utilizing and related cellular processes to allow
organisms to enter a stable hypometabolic state. Anoxia tolerance is also
supported by selective gene expression as revealed by recent studies using cDNA
library and DNA array screening. New studies with both adult T. scripta elegans
and hatchling C. picta marginata have identified prominent groups of genes that
are up-regulated under anoxia in turtle organs, in several cases suggesting
aspects of cell function and metabolic regulation that have not previously been
associated with anaerobiosis. These groups of anoxia-responsive genes include
mitochondrially-encoded subunits of electron transport chain proteins, iron
storage proteins, antioxidant enzymes, serine protease inhibitors, transmembrane
solute carriers, neurotransmitter receptors and transporters, and shock proteins.
PMID- 17035058
TI - Distribution and abundance of nutrient transporter mRNA in the intestinal tract
of the black bear, Ursus americanus.
AB - End products of digestion are absorbed by the body through the action of
transporter proteins expressed on the apical membrane of intestinal epithelial
cells. We investigated the mRNA abundance and distribution of a peptide
transporter (PepT1), a glucose transporter (SGLT1), two amino acid transporters
(NBAT and b(o,+)AT), and a digestive enzyme, aminopeptidase N (APN), in the
intestinal tract of black bears (Ursus americanus). Intestinal total RNA was
isolated from 10 bears and abundance of PepT1, SGLT1, NBAT, b(o,+)AT, and APN
mRNA were determined by Northern blots. Abundance of PepT1 (P<0.05), APN
(P<0.05), and SGLT1 (P<0.0001) changed quadratically from the proximal to distal
intestine with abundance being greatest in the midregion. Abundance of b(o,+)AT
mRNA increased linearly (P<0.05) from the proximal to distal intestine. The
number of molecules of mRNA/ng of total RNA for each gene was determined using
Real-Time PCR. PepT1 mRNA was present at 10-fold or greater levels than amino
acid transporter mRNA in all segments of the intestine, suggesting that di- and
tripeptides constitute a major form in which amino acids are absorbed in the
black bear. The abundance of NBAT and b(o,+)AT mRNA was greater towards the
distal intestine, suggesting a role in salvaging unabsorbed amino acids.
PMID- 17035059
TI - IGF regulation of neutral amino acid transport in the BeWo choriocarcinoma cell
line (b30 clone): evidence for MAP kinase-dependent and MAP kinase-independent
mechanisms.
AB - OBJECTIVE: IGF-1 and IGF-1 receptors are major determinants of fetal growth and
are expressed primarily on the maternal-facing surface of the syncytiotrophoblast
cell membrane in the human placenta. IGF-1 regulates fetal growth, in part, by
regulating amino acid transport across the placenta. The objective of these
studies was to study the role of IGF-1 and its signaling pathway in regulating
neutral amino acid transport in a human trophoblast cell culture model. DESIGN:
The regulation of neutral amino acid transport by IGF-1 was studied in cultured
BeWo(b30) choriocarcinoma cells using the non-metabolizing amino acid analog,
[(3)H]-alpha-aminoisobutyric acid (AIB). Transport in the absence of Na was used
to distinguish system L from total AIB transport. Similarly, Na-dependent
transport in the presence of excess methyl-AIB (MeAIB) permitted discrimination
of systems A (MeAIB-sensitive) and ASC (MeAIB-insensitive). Specific inhibitors
of intracellular signaling pathways were then used to determine the signaling
pathway utilized by IGFs to regulate each amino acid transport system.
Specificity of inhibition was assessed using specific markers of p70 S6 kinase
activity and MAP kinase activation. RESULTS: Maximal stimulating concentrations
of IGF-I (100 ng/ml) stimulated AIB transport by 30-40% exclusively through
system A. Wortmannin (100 nM), an inhibitor of PI-3-kinase activity, inhibited
all IGF-I-stimulated transport. Rapamycin (100 ng/ml), an inhibitor of p70 S6
kinase, and bisindolylmaleimide, an inhibitor of protein kinase C (PKC), had no
effect. PD-098059 (50 miccroM), an inhibitor of MAP kinase activation, inhibited
20-30% of basal AIB transport but did not inhibit IGF-I-stimulated transport
under the conditions studied. IGF-1 did not increase steady state mRNA levels of
the system A transporters, SNAT1 and SNAT2, suggesting IGF-1 stimulates transport
via post-transcriptional mechanisms. CONCLUSIONS: These data demonstrate that IGF
I stimulates neutral amino acid transport system A by a PI3-kinase dependent,
post-transcriptional pathway in the BeWo(b30) cell line. Additionally, system A
activity appear to be sensitive to MAP kinase-dependent pathways not regulated by
IGFs.
PMID- 17035060
TI - [Lung cancer: is there a place for elective nodal irradiation?].
AB - The use of conformal radiotherapy in lung cancer has considerably evolved with
the advent of improved staging technologies and methods of radiation delivery.
Patients with limited disease, inoperable for medical reasons, may be treated
with conformal radiotherapy alone; patients with more advanced disease are
treated with combined chemo-radiotherapy. If local control may be improved by
radiotherapy dose escalation according to several studies, toxicity and more
particularly pulmonary toxicity seems to be related to radiation volume. Thus the
use of elective nodal irradiation is being questioned. Data for early stage
(stage I) non-small-cell lung cancer treated with conformal radiotherapy or
stereotactic hypofractionated radiotherapy strongly supports the use of smaller
fields that do not incorporate elective nodal regions; local control and survival
rates approach those of surgical series. In locally advanced non-small cell lung
cancer, eliminating elective nodal irradiation allows to maximize tumor dose and
minimize normal tissue toxicity in combined modality treatments; results are
encouraging. The use of staging modalities such as positron emission tomography
and eventually oesophageal ultrasonography is increasing, allowing to encompass
the tumor volume with more accuracy. Several studies have confirmed that involved
field irradiation results into a regional nodal rate of less than 10%. Further
larger-scale studies would be needed to definitely establish "no elective nodal
irradiation" as a standard in non-small cell lung cancer. There are very few data
concerning small cell lung cancer.
PMID- 17035061
TI - [Prostate localization systems for prostate radiotherapy].
AB - The development of sophisticated conformal radiation therapy techniques for
prostate cancer, such as intensity-modulated radiotherapy, implies precise and
accurate targeting. Inter- and intrafraction prostate motion can be significant
and should be characterized, unless the target volume may occasionally be missed.
Indeed, bony landmark-based portal imaging does not provide the positional
information for soft-tissue targets (prostate and seminal vesicles) or critical
organs (rectum and bladder). In this article, we describe various prostate
localization systems used before or during the fraction: rectal balloon,
intraprostatic fiducials, ultrasound-based localization, integrated CT/linear
accelerator system, megavoltage or kilovoltage cone-beam CT, Calypso 4D
localization system tomotherapy, Cyberknife and Exactrac X-Ray 6D. The clinical
benefit in using such prostate localization tools is not proven by randomized
studies and the feasibility has just been established for some of these
techniques. Nevertheless, these systems should improve local control by a more
accurate delivery of an increased prescribed dose in a reduced planning target
volume.
PMID- 17035062
TI - Genetic determinants of acute inflammation regulate Salmonella infection and
modulate Slc11a1 gene (formerly Nramp1) effects in selected mouse lines.
AB - Two lines of mice selected to produce maximal (AIRmax) or minimal (AIRmin) acute
inflammatory reactions (AIR) differ in their susceptibility to infection by
Salmonella enterica serotype Typhimurium (S. Typhimurium). The LD(50) for AIRmax
mice is 1000 times higher than that observed for AIRmin mice, and higher
frequencies of Slc11a1 alleles (known to confer either resistance (R) or high
susceptibility (S) to S. Typhimurium) were consistently found in AIRmax and
AIRmin mouse lines, respectively. In order to evaluate the effect of the
quantitative trait loci (QTL) segregated in AIRmax and AIRmin mice on Slc11a1
dependent susceptibility to S. Typhimurium, the R and S alleles were fixed in
homozygosity in AIRmax and AIRmin backgrounds by genotype assisted breedings.
These new lines were named AIRmax(RR), AIRmax(SS), AIRmin(RR), and AIRmin(SS).
Acute inflammation of Slc11a1(RR) animals was more severe in comparison to their
Slc11a1(SS) counterparts, implicating Slc11a1 (or other linked genes) in AIR
regulation. The LD(50) of S. Typhimurium was 800-times higher for AIRmax(SS) than
for AIRmin(SS), demonstrating that AIR QTL can act as modifiers of the
Slc11a1(SS) susceptibility gene. Four microsatellite markers for S. Typhimurium
susceptibility QTL described in other mouse lines showed specific allele fixation
in AIRmax or AIRmin mice, suggesting that these chromosomal regions also
segregate with inflammatory phenotypes.
PMID- 17035063
TI - Finite element modelling of the pelvis: inclusion of muscular and ligamentous
boundary conditions.
AB - Previous finite element studies of the pelvis, including subject-specific studies
have made extensive simplifications with regards to the boundary conditions used
during analysis. Fixed boundary conditions are generally utilised at the pubis
and superior part of the ilium. While it can be demonstrated that these models
provide a close match for certain in vitro experiments that use similar boundary
conditions, the resulting stress-strain fields in the cortex in particular are
unlikely to be those found in vivo. This study presents a finite element analysis
in which the pelvis is supported by muscular and ligamentous boundary conditions,
applied using spring elements distributed over realistic attachment sites. The
analysis is compared to an analysis in which the pelvis is restrained by fixed
boundary conditions applied at the sacro-iliac joints. Striking differences in
the stress-strain fields observed in cortical bone in particular, are found
between the two analyses. The inclusion of muscular and ligamentous boundary
conditions is found to lower the occurrence of stress concentrations within the
cortex.
PMID- 17035064
TI - A control system for automatic electrical stimulation of abdominal muscles to
assist respiratory function in tetraplegia.
AB - People with tetraplegia have poor respiratory function leading to limited tidal
volume (V(T)) and reduced cough peak flow (CPF). These problems may cause
respiratory failure during the initial admission or subsequent intercurrent
illness. Electrical stimulation of the abdominal muscles during expiration can
improve respiratory function by increasing V(T) and CPF. We developed a novel
control system to automatically trigger muscle stimulation, synchronised with the
subject's voluntary respiratory activity. The system was tested in four subjects
with a functionally complete lesion at level C4 to C6, aged between 16 and 46
years, 3 months to 5 years post injury, who were breathing spontaneously. The
algorithm delivered automatic stimulation patterns, detecting cough and quiet
breathing while suppressing stimulation during other activities such as speaking.
Marked increases in V(T) (between 9% and 71% of baseline) and CPF (between 31%
and 54% of baseline) were observed, suggesting that the technique may have
potential use in both acute and established tetraplegia to increase minute
ventilation and to improve cough clearance of secretions.
PMID- 17035065
TI - Preparation of microbubble suspensions by co-axial electrohydrodynamic
atomization.
AB - In this paper we report a novel method, based on co-axial electrohydrodynamic
jetting, for the preparation of microbubble suspensions containing bubbles <10
microm in size and having a narrow size distribution. No selective filtration is
necessary and the suspensions are produced directly by the process. To
demonstrate the method, glycerol was used as the liquid medium, flowing in the
outer needle of the co-axial twin needle arrangement and undergoing
electrohydrodynamic atomization in the stable cone-jet mode while air flowed
through the inner needle at the same time. At zero applied voltage a hollow
stream of liquid flowed from the outer needle. When the applied voltage was
increased, eventually the hollow stream became a stable cone-jet and emitted a
microthread of bubbles, which were collected in a container of glycerol to obtain
microbubble suspensions. The size of the microbubbles was measured via optical
microscopy and laser diffractometry. Several microbubble suspensions were
prepared and characterised and the size distribution was found to be critically
dependent on the ratio (n) of flow rates of liquid/air and, in particular the
flow rate of the air. At n=1.5, with the flow rate of air set at approximately
1.7 microl/s, a microbubble suspension containing bubbles in the size range 2-8
microm was obtained.
PMID- 17035066
TI - Adverse events and the vertebral artery: can they be averted?
PMID- 17035067
TI - Gene expression profiling reveals complex changes following MEK-EE expression in
cardiac myocytes.
AB - The activation of the MEK/ERK pathway has been implicated in the proliferative
growth of many tissues, however in the heart it has been linked with hypertrophic
growth of the individual cardiac myocytes. We have explored the transcriptional
consequences of prolonged ERK1/2 activation in cardiac myocytes following the
adenoviral overexpression of a constitutively active form of MEK, MEK-EE.
Analysis of microarray data obtained using full rat genome arrays showed >2000
gene expression changes in response to MEK-EE overexpression for 24h. We observed
similar numbers of genes upregulated and downregulated. The genes were involved
in diverse processes including cell structure, metabolism and intracellular
signalling. There were also changes in the pro- and ani-apoptotic genes as well
as downregulation of the antioxidant enzymes, Mn superoxide dismutase, catalase
and thioredoxin 2. Our results reveal the complexity of transcriptional changes
that follow the activation of the ERK signalling pathway in these cells and
suggest that activation of this MAPK pathway impinges on diverse cellular
functions.
PMID- 17035068
TI - Trafficking of osteonectin by retinal pigment epithelial cells: evidence for
basolateral secretion.
AB - Osteonectin is a glycoprotein that modulates several aspects of cellular
behaviour including proliferation and adhesion. The retinal pigment epithelium
forms a continuous monolayer of polarised cells immediately bellow the
neuroretina, and is integral to the homeostasis of photoreceptor cells. While
osteonectin is expressed by normal retinal pigment epithelium in situ, its
expression is significantly increased in retinal pigment epithelial cells
associated with several common retinal diseases. This pattern of expression
implies an important role for osteonectin in the biology of retinal pigment
epithelial cells. However, the trafficking, processing, and eventual fate of
osteonectin in these cells is not clear at present. Although the theoretical
report of a leader sequence within the osteonectin open reading frame and its
extracellular presence in some tissues indirectly support secretion of the
protein, there is no direct experimental demonstration of the secretion route to
date. As a first step towards understanding the role of osteonectin in retinal
pigment epithelium, we studied the intracellular distribution and trafficking of
the protein in living cells. Here, we present experimental evidence that a
precursor osteonectin fusion protein is targeted to the endoplasmic
reticulum/Golgi pathway, with a likely basal secretion in retinal pigment
epithelial cells. In addition, we show that the precursor osteonectin protein
having the leader sequence masked fails to undergo secretion leading to cell
death, a phenotype which may be of relevance not only for retinal pathology, but
also for other diseases such as the bone disorder known as pseudoachondroplasia
that is associated with a lack of osteonectin secretion.
PMID- 17035069
TI - Photoperiodic control of flowering: not only by coincidence.
AB - The timing of floral transition has a direct impact on reproductive success. One
of the most important environmental factors that affect the transition is the
change in day length (photoperiod). Classical experiments imply that plants
monitor photoperiods in the leaf, and transmit that information coded within an
elusive signal dubbed florigen to the apex to reprogram development. Recent
advances in Arabidopsis research indicate that the core of the day-length
measurement mechanism lies in the circadian regulation of CONSTANS (CO)
expression and the subsequent photoperiodic induction of the expression of
FLOWERING LOCUS T (FT) gene, which might encode a major component of florigen. In
this review, we introduce current perspectives on how, when and where the floral
signal is generated.
PMID- 17035070
TI - NO signal at the crossroads: polyamine-induced nitric oxide synthesis in plants?
AB - Polyamines, such as spermine, spermidine and putrescine, are ubiquitous
polycationic compounds that are produced by almost all living organisms,
including plants, animals, fungi and bacteria. Polyamines are multifunctional and
interact with polyanionic biomolecules such as DNA or protein. However, despite
their potential significance, the polyamine-dependent signal transduction system
has not been revealed yet. Ni Ni Tun and colleagues have recently reported a
possible linkage between polyamine and nitric oxide (NO), another ubiquitous
signalling molecule.
PMID- 17035071
TI - Futile cycling at the plasma membrane: a hallmark of low-affinity nutrient
transport.
AB - Plant nutrient acquisition from concentrated soil solutions is governed by low
affinity transport systems in the plasma membranes of root cells. In this Opinion
article, we illustrate that for six major nutrient ions, in addition to influx
mediation by low-affinity transporters, high rates of ion cycling at the plasma
membrane are a hallmark of nutrient transport at elevated external
concentrations. This phenomenon is characterized by high rates of ion influx and
concurrent high efflux of the same ion, resulting in efflux:influx ratios close
to 1. Prolonged maintenance of futile cellular ion cycling can be energetically
unfavorable and detrimental to plant growth and survival. We discuss how ion
cycling can contribute to the toxicities of ions such as Na(+) and NH(4)(+) in
the low-affinity range of ion provision. We also argue that cellular ion cycling
makes the reliable measurement of ion influxes in the low-affinity range a
formidable challenge.
PMID- 17035073
TI - Interactions between macromolecules and ions: The Hofmeister series.
AB - The Hofmeister series, first noted in 1888, ranks the relative influence of ions
on the physical behavior of a wide variety of aqueous processes ranging from
colloidal assembly to protein folding. Originally, it was thought that an ion's
influence on macromolecular properties was caused at least in part by 'making' or
'breaking' bulk water structure. Recent time-resolved and thermodynamic studies
of water molecules in salt solutions, however, demonstrate that bulk water
structure is not central to the Hofmeister effect. Instead, models are being
developed that depend upon direct ion-macromolecule interactions as well as
interactions with water molecules in the first hydration shell of the
macromolecule.
PMID- 17035074
TI - Unnatural base pair systems for DNA/RNA-based biotechnology.
AB - The development of unnatural, extra base pairs could expand genetic information,
by enabling the site-specific incorporation of functional components into nucleic
acids and proteins. Researchers have been trying to create unnatural base pairs
by drawing upon non-standard hydrogen-bonding topologies, shape complementarity,
and/or hydrophobic interfaces, to confer sufficient selectivity and efficiency to
work with the natural A-T(U) and G-C base pairs in replication, transcription and
translation. The development of artificial genetic systems has been broadly
advanced by combining the extra base pairs with modified natural components,
including the base pairs, substrates and polymerase enzymes.
PMID- 17035075
TI - Electron-conducting redox hydrogels: Design, characteristics and synthesis.
AB - Redox hydrogels constitute the only electron-conducting phase in which water
soluble chemicals and biochemicals dissolve and diffuse. The combination of
solubility and diffusion makes the electron-conducting gels permeable to water
soluble biochemicals and chemicals. The electron-conducting redox hydrogels serve
to electrically connect the redox centers of enzymes to electrodes, enabling
their use whenever leaching of electron-shuttling diffusional redox mediators
must be avoided, which is the case in subcutaneously implanted biosensors for
diabetes management and in miniature, potentially implantable, glucose-O2 biofuel
cells. Because the hydrogels envelope the redox enzymes, they electrically wire
the reaction centers to electrodes irrespective of spatial orientation and
connect to electrode redox centers of multiple enzyme layers. Hence, the attained
current densities of enzyme substrate electrooxidation or electroreduction are
much higher than with enzyme monolayers packed onto electrode surfaces.
PMID- 17035076
TI - Non-self recognition and programmed cell death in filamentous fungi.
AB - Non-self recognition resulting in programmed cell death is a ubiquitous
phenomenon in filamentous ascomycete fungi and is termed heterokaryon
incompatibility (HI). Recent analyses show that genes containing predicted HET
domains are often involved in HI; however, the function of the HET domain is
unknown. Autophagy is induced as a consequence of HI, whereas the presence of a
predicted transcription factor, VIB-1, is required for HI. Morphological features
associated with apoptosis in filamentous fungi are induced by various stresses
and drugs, and also during HI. Future analyses will reveal whether common or
different genetic mechanisms trigger death by non-self recognition and death by
various environmental onslaughts.
PMID- 17035077
TI - A vibrational spectroscopic study of perhamite, an unusual silico-phosphate.
AB - The silico-phosphate mineral perhamite has been studied using a combination of
electron and vibrational spectroscopy. SEM photomicrographs reveal that perhamite
morphology consists of very thin intergrown platelets that can form a variety of
habits. Infrared spectroscopy in the hydroxyl-stretching region shows a number of
overlapping bands which are observed in the range 3581-3078 cm(-1). These
wavenumbers enable an estimation to be made of the hydrogen bond distances in
perhamite: 3.176(0), 2.880(5), 2.779(6), 2.749(3), 2.668(1) and 2.599(7)A.
Intense Raman bands are observed in the region 1110-1130 and 966-996 cm(-1) and
are assigned to the SiO(4) and PO(4) symmetric stretching modes. Other bands are
observed in the range 1005-1096 cm(-1) and are attributed to the nu(3)
antisymmetric bending modes of PO(4). Some low intensity bands around 874 cm(-1)
were discovered and remain unclassified. Bands in the low-wavenumber region are
assigned to the nu(4) and nu(2) out-of-plane bending modes of the OSiO and PO(4)
units. Raman spectroscopy is a useful tool in determining the vibrational
spectroscopy of mixed hydrated multi-anion minerals such as perhamite.
Information on such a mineral would be difficult to obtain by other means.
PMID- 17035078
TI - A new spectrophotometric method for the determination of finasteride in tablets.
AB - A simple, rapid, accurate, precise and sensitive colorimetric method for the
determination of finasteride in tablets is described. The proposed methods are
based on the formation of ion-pair complexes between the examined drug with
bromophenol blue (BPB), bromocresol green (BCG) and bromothymol blue (BTB), which
can be measured at the optimum lambda(max). Beer's law is obeyed in the
concentration ranges 3.0-15.0, 3.0-15.0 and 5.0-20 microg/mL with BPB, BCG and
BTB, respectively. The detection limits of FIN was found to be 1.16 microg/mL for
BPB, 1.17 for BCG, 1.76 microg/mL for BTB. All the methods gave similar results
and were validated for selectivity, linearity, precision and sensitivity. The
proposed methods were directly and easily applied to the pharmaceutical
preparation with accuracy, resulting from recovery experiments between 100.11 and
100.33% for BPB, 100.17 and 100.67% for BCG and 100.33 and 100.60% for BTB
methods. The low relative standard deviation values indicate good precision and
high recovery values indicate accuracy of the proposed methods. The proposed
methods have been applied to the determination of drug in commercial tablets.
Results obtained from the analysis of commercial preparations with the proposed
methods are in good agreement with those obtained with the official HPLC method.
PMID- 17035079
TI - Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and
acebutolol hydrochloride.
AB - Simple and sensitive spectrophotometric and spectrofluorimetric methods are
described for analysis of acyclovir and acebutolol hydrochloride. The proposed
methods are based on oxidation of the selected drugs with cerium(IV) ion in
acidic medium with subsequent measurement of either the decrease in absorbance at
320nm or the fluorescence intensity of the produced cerous(III) ion at 361-363nm
(excitation at 250nm). Beer's law obeyed from 2 to 8, 0.25 to 2.5microgcm-1
acyclovir, 1 to 7 and 0.25 to 2.5microgml-1 acebutolol hydrochloride, using the
spectrophotometric and spectrofluorimetric method, respectively. The proposed
method were successfully applied for determination of the selected drugs in their
pharmaceutical preparations with good recoveries.
PMID- 17035080
TI - Design and implementation of an ICU incident registry.
AB - Due to its complexity intensive care is vulnerable to errors. On the ICU adults
of the AMC (Amsterdam, The Netherlands) the available registries used for error
reporting did not give insight in the occurrence of unwanted events, and did not
lead to preventive measures. Therefore, a new registry has been developed on the
basis of a literature study on the various terms and definitions that refer to
unintended events, and on the methods to register and monitor them. As this
registry intends to provide an overall insight into errors, a neutral term
('incident') -- which does not imply guilt or blame -- has been sought together
with a broad definition. The attributes of an incident further describe the
unwanted event, but they should not form an impediment for the ICU nurses and
physicians to report. The properties of a registry that contribute to making it
accessible and user friendly have been determined. This has resulted in an
electronic registry where incidents can be reported rapidly, voluntarily,
anonymously and free of legal consequences. Evaluation is required to see if the
new registry indeed provides the ICU management with the intended information on
the current situation on incidents. For further refinement of the design,
additional development and adjustments are required. However, we expect that the
awareness of errors of the ICU personnel has already improved, forming the first
step to increased patient safety.
PMID- 17035081
TI - Is the genotyping of hepatitis B virus of clinical help in patient management?
PMID- 17035082
TI - Umbilical cord blood screening for cytomegalovirus DNA by quantitative PCR.
AB - BACKGROUND: Cytomegalovirus (CMV) infection, which is the most common
congenitally transmitted infection, affects approximately 1% of neonates
worldwide. Despite its prevalence, no convenient screening test for neonatal CMV
infection has been implemented. OBJECTIVE: The purpose of this pilot study was to
evaluate the feasibility and yield of screening umbilical cord blood for CMV DNA
emiaby quantitative PCR. STUDY DESIGN: Umbilical cord blood was tested for CMV
DNAemia using a commercial quantitative PCR assay. Maternal CMV serostatus at the
time of delivery was assessed by testing for CMV IgG and IgM antibodies in serum.
CONCLUSIONS: Screening for congenital CMV infection with PCR is easily
incorporated into routine labor and delivery care using discarded cord blood
specimens to identify neonates whose infection is otherwise undiagnosed. Among
433 infants tested, two (0.5%) had DNAemia detected in cord blood, one of whom
was symptomatic, and both of whose mothers were CMV IgG positive and IgM
negative. Viremic neonates identified by screening with PCR may be at high risk
of developing long-term neurological complications of CMV infection and cannot
reliably be identified using clinical presentation or maternal serology. Because
of its convenience, cord blood CMV screening with PCR should be further
investigated for incorporation into neonatal screening protocols.
PMID- 17035083
TI - Non-indicated oral anticoagulation in left ventricular
hypertrabeculation/noncompaction may jeopardize these patients.
PMID- 17035084
TI - Polyethyleneterephthalate provides superior retention of endothelial cells during
shear stress compared to polytetrafluoroethylene and pericardium.
AB - BACKGROUND: Polyethyleneterephthalate (PET) and polytetrafluoroethylene (PTFE)
are polymers successfully used as large diameter arterial grafts for peripheral
vascular surgery. However, these prosthetic grafts are rarely used for coronary
bypass surgery because of their low patency rates. Endothelialisation of the
lumenal surface of these materials may improve their patency. This study aimed to
compare the endothelialisation of PET, PTFE and pericardium by examining their
seeding efficiency over time and the effect of various shear stresses on
retention of endothelial cells. METHODS: Ovine endothelial cells at
4x10(5)cells/cm(2) were seeded onto PET, PTFE and pericardium, and cultured for 1
168 hours. Cell coverage was determined via en face immunocytochemistry and cell
retention was quantified after being subjected to shear stresses ranging from
0.018 to 0.037N/m(2) for 15, 30 and 60 minutes. RESULTS: Endothelial cells
adhered to all of the materials one hour post-seeding. PET exhibited better cell
retention rate, ranging from 66.9+/-5.6% at 0.018N/m(2) for 15min to 44.7+/-1.9%
at 0.037N/m(2) for 60 minutes, when compared to PTFE and pericardium (p<0.0001,
three-way ANOVA). CONCLUSION: PET shows superior retention of endothelial cells
during shear stress compare to PTFE and pericardium.
PMID- 17035086
TI - The origin and age of Plasmodium vivax.
AB - The evolutionary history of Plasmodium vivax has recently been addressed in terms
of its origin as a parasite of humans and the age of extant populations. The
consensus is that P. vivax originated as a result of a host switch from a non
human primate to hominids and that the extant populations did not originate as
recently as previously proposed. Here, we show that, in a comparison of parasite
isolates from across the world, Asian populations of P. vivax are the oldest. We
discuss how this result, together with the phylogenetic evidence that P. vivax
derived from Plasmodium found in Southeast Asian macaques, is most simply
explained by assuming an Asian origin of this parasite. Nevertheless, the
available data show only the tip of the iceberg. We discuss how sampling might
affect time estimates to the most recent common ancestor for P. vivax populations
and suggest that spatially explicit estimates are needed to understand the
demographic history of this parasite better.
PMID- 17035087
TI - Species accumulation curves and their applications in parasite ecology.
AB - Species accumulation curves (SACs) chart the increase in recovery of new species
as a function of some measure of sampling effort. Studies of parasite diversity
can benefit from the application of SACs, both as empirical tools to guide
sampling efforts and predict richness, and because their properties are
informative about community patterns and the structure of parasite diversity.
SACs can be used to infer interactivity in parasite infracommunities, to
partition species richness into contributions from different spatial scales and
different levels of the host hierarchy (individuals, populations and communities)
or to identify modes of community assembly (niche versus dispersal). A historical
tendency to treat individual hosts as statistically equivalent replicates
(quadrats) seemingly satisfies the sample-based subgroup of SACs but care is
required in this because of the inequality of hosts as sampling units. Knowledge
of the true distribution of parasite richness over multiple host-derived and
spatial scales is far from complete but SACs can improve the understanding of
diversity patterns in parasite assemblages.
PMID- 17035088
TI - Intestinal allergy expels hookworms: seeing is believing.
AB - It is unclear how immunity limits hookworm infection. Australian researchers,
using capsule and conventional gastrointestinal endoscopy in volunteers
inoculated with Necator americanus, have reported that virtually all larvae reach
the intestine within six weeks. Unlike the neutral response surrounding resident
hookworms, newly arrived adults provoke an eosinophilic enteropathy. This
allergic reaction curtails the attachment of hookworms and accompanies the
passage of additional worms as they are expelled from the proximal small
intestine.
PMID- 17035089
TI - Rapid phenotypic assay of antimycobacterial susceptibility pattern by direct
mycobacteria growth indicator tube and phage amplified biological assay compared
to BACTEC 460 TB.
AB - The performance of antimycobacterial susceptibility testing for the first line
drugs (isoniazid, streptomycine, rifampicin and ethambutol) with mycobacteria
growth indicator tube (MGIT) and by bacteriophage amplified biological assay by
FAST-plaque TB-MDR were compared to automated radiometric BACTEC 460 TB system.
This study was carried on 84 sputum samples of positive Zhiel-Neelsen (ZN)
smears. Sputum samples were subjected to culture and antimycobacterial
susceptibility testing by BACTEC 460 TB. Samples were also tested by direct
susceptibility tests for isoniazid (INH), ethambutol, rifampicin (RIF) and
streptomycine by MGIT. Sensitive and resistant isolates for RIF were further
studied by FAST-plaque TB-MDR for RIF resistance. The commonest resistance
pattern by BACTEC 460 TB was for INH (32%) followed by RIF (24%) either alone or
in combination with other drugs. Multiple drugs resistance was 20%. The agreement
between BACTEC 460 TB and direct MGIT for resistant strains was 100% for INH and
ethambutol, 91.7% for rifampicin, 80% for streptomycine and was 90% for MDR. FAST
plaque TB-MDR detected correctly all RIF resistant strains and 97.2% of the
sensitive strains. For majority of strains direct susceptibility tests were
available within 6.34-6.404 days (95% confidence interval) with direct
mycobacteria growth tube, while results for FAST-plaque TB-MDR appear within 10.5
11.5 days from the time that the sputum was received in the laboratory (95%
confidence interval). From this study, we could conclude that direct MGIT AST is
the quickest method for screening antimycobacterial susceptibility pattern for
the drugs commonly used (INH, RIF, etambutol, streptomycin) as results were
available within 6.34-6.404 days. Also FAST-plaque TB-MDR method is accurate for
detection of rifampicin resistance after primary culture which can be used as a
surrogate marker for presence of MDR strains and the results were available
within 10.5-11.5 days.
PMID- 17035090
TI - Salvaging of liquid-preserved O-positive and O-negative red blood cells by
rejuvenation and freezing.
AB - BACKGROUND: The RBC inventory is subject to seasonal highs and lows. When the
inventory is high, units may be lost due to outdating and when the inventory is
low, elective surgical procedures may have to be postponed until sufficient blood
is available. This study was done to determine if universal donor O-positive and
O-negative RBC subjected to various methods of transportation could subsequently
be rejuvenated and frozen to be used for inventory control with satisfactory
results. MATERIALS AND METHODS: Units of blood were collected at two different
military facilities and processed as whole blood (WB) or packed RBC. The liquid
stored WB or RBC units were subjected to transportation, with or without air
dropping, as part of a military exercise. The units were kept at 4 degrees C with
wet ice during transportation to the NBRL for evaluation. The quality of the
liquid preserved RBC was evaluated before rejuvenation and freezing and after the
freeze-thaw-wash procedure. Following frozen storage at -80 degrees C, the RBC
were thawed and deglycerolized using the Haemonetics 115 cell washer. In addition
to measurements of freeze-thaw and freeze-thaw-wash recovery, other in vitro
assessments of RBC quality were made. RESULTS: The results demonstrate acceptable
quality for RBC subjected to transportation, with or without air dropping,
following rejuvenation and freezing. CONCLUSION: We consider it a prudent
practice for liquid preserved O-negative and O-positive RBC collected at various
blood collection sites to be sent to a specific facility where the universal
donor RBC can be rejuvenated and frozen as a stockpile for inventory control.
PMID- 17035091
TI - Release of PMN elastase, TGF-beta1 and neopterin during blood storage; unfiltered
versus filtered blood.
AB - Release of inflammatory mediators from blood cells during prestorage leukocyte
filtration may result in recipient immune suppression. To investigate the effects
of prestorage leukocyte filtration on the quality of blood components, twenty
four blood units were collected from healthy donors and randomised into 3 groups.
Eight units were stored as whole blood, eight units were separated into plasma,
red blood cells (RBC) and buffy coat and eight units were collected and filtered
through the ASAHI RZ 2000 leukocyte filter and separated into plasma and RBC. The
units were stored for 35 days. Samples were collected weekly for analyses of
polymorphonuclear elastase (PMN elastase), transforming growth factor-beta1 (TGF
beta1) and neopterin. PMN elastase and neopterin increased during storage of
whole blood and RBC. From the beginning and throughout storage, PMN elastase was
increased in filtered plasma as compared with unfiltered plasma. Filtration per
se did not influence the neopterin concentration in plasma or RBC. TGF-beta1
increased in plasma and RBC during storage. In filtered plasma, an elevation of
the TGF-beta1 concentration was observed from the start of storage. The TGF-beta1
levels were higher in filtered plasma compared with unfiltered plasma. Prestorage
leukocyte filtration increased the release of PMN elastase and TGF-beta1 in
plasma and RBC.
PMID- 17035092
TI - Expression of human liver HSPGs on acute myeloid leukemia.
AB - Heparan sulfate proteoglycans (HSPGs) play important biological roles in cell
matrix adhesion processes and are essential regulators of growth actions. The
expression of the different HSPGs in itself is tightly regulated providing strict
controls on the activities of the bound ligands. Human liver is a target for a
number of pathogens, and HSPGs have been demonstrated in several cases to play a
pivotal role in infectivity. Despite HSPGs important biological functions, little
is known about its cell-specific distribution patterns. Human liver HSPG was
isolated, and a specific monoclonal antibody (mAb) 1E4-1C2 was produced.
Distribution of HSPG reactive to this mAb was studied in normal blood cells,
hematopoietic cell lines and blood cells isolated from patients with various
hematologic disorders using indirect immunofluorescence. There was no expression
of molecules recognized by this mAb on lymphoid (Daudi, Jurkat, SupT-1) and
monocytoid (U937) cell lines. Peripheral blood cells, normal bone marrow,
together with leukocytes isolated from patients with acute lymphoblastic
leukemia, chronic myelocytic leukemia, Hodgkin's disease or Non-Hodgkin's
lymphoma, were also negative. In contrast, 1E4-1C2 showed significant positive
results on human myeloid cell lines HL-60 and K562. Moreover, it is interesting
that this mAb also recognized epitopes on leukocytes isolated from acute
myeloblastic leukemia. These results suggest that malignancies of cells in
myeloid lineage may cause expression of HSPGs that are detected by this specific
mAb, making it a potential co-marker for the diagnosis of acute myeloid leukemia.
PMID- 17035093
TI - Characterization of a cytotoxic CD57+ T cell subset from patients with pulmonary
tuberculosis.
AB - We investigated the proportion, phenotype, and cytotoxicity of CD8+CD57+ and CD57
T cells in peripheral blood from 20 tuberculosis (TB)-patients and 20 healthy
tuberculin skin test-positive donors. Our results showed an increase in CD8+CD57+
T cells from TB-patients as compared with those from age-matched healthy donors
(p<0.0001). CD8+CD57+ T cells from TB-patients expressed CD69, perforin, granzyme
A, and a CD28-CD62L-CD161- phenotype without recognition for the alpha
galactosylceramide-CD1d complex. This cell subset also expressed TNF-alpha and
IFN-gamma, under phorbol-myristate-acetate/ionomycin stimulation. Interestingly,
the cytotoxicity against autologous monocytes was higher in CD57- cells from TB
patients and donors than their CD57+ counterparts, in the presence of
Mycobacterium tuberculosis H37Rv culture filtrate. However, only CD8+CD57+ T
cells from TB-patients exhibited spontaneous cytotoxicity against monocytes in
the absence of antigen. Our results suggest that CD8+CD57+ T cells are a subset
of effector cells that could be helpful to evaluate the cell-mediated immune
response to M. tuberculosis.
PMID- 17035094
TI - Murine experimental autoimmune gastritis models refractive to development of
intrinsic factor autoantibodies, cobalamin deficiency and pernicious anemia.
AB - Researchers have developed murine lymphopenic, non-lymphopenic, transgenic,
spontaneous and infectious agent based models to induce an experimental
autoimmune gastritis (EAG) for the study of human organ-specific autoimmune
disease. These models result in a chronic inflammatory mononuclear cell
infiltrate in the gastric mucosa, destruction of parietal and zymogenic cells
with autoantibodies reactive to the gastric parietal cells and the gastric H+/K+
ATPase (ATP4), arguably hallmarks of a human autoimmune gastritis (AIG). In the
case of AIG, it is well documented that, in addition to parietal cell antibodies
being detected in up to 90% of patients, up to 70% have intrinsic factor
antibodies with the later antibodies considered highly specific to patients with
pernicious anemia. This is the first report specifically investigating the
occurrence of intrinsic factor antibodies, cobalamin deficiency and pernicious
anemia in EAG models. We conclude, in contrast to AIG, that, in the three EAG
models examined, intrinsic factor is not selected as a critical autoantigen.
PMID- 17035095
TI - Comparison of endothelial function in the carotid artery between normal and short
term hypercholesterolemic rabbits.
AB - The present study was undertaken to investigate and compare the vascular function
in carotid arteries isolated from normal short-term hypercholesterolemic rabbits.
Rabbits were fed normal or 0.5% cholesterol chow for 5 weeks. The tension of
isolated carotid artery rings was measured isometrically. Serum lipid levels were
measured and morphometric analysis was performed. And content of nitrate/nitrite
in the carotid artery was also determined. In the carotid artery precontracted by
phenylephrine, the cholesterol chow diet administered for 5 weeks decreased
acetylcholine-induced relaxation at only middle concentrations, though it
significantly increased the content of nitrate/nitrite, the sum of stable nitric
oxide metabolites, in the carotid artery. Cholesterol chow for 5 weeks had no
influence on sodium nitroprusside-induced relaxation in the carotid artery. The
N(G)-nitro-L-arginine- and indomethacin-resistant endothelium-dependent
relaxation induced by acetylcholine was significantly decreased in rabbits
receiving the cholesterol chow as compared to rabbits receiving the control diet.
The resistant part of acetylcholine-induced relaxation was significantly
inhibited when the carotid artery was treated with glibenclamide, a selective
inhibitor of ATP-sensitive K(+) channels, 4-aminopyridine, an inhibitor of
voltage-dependent K(+) channels, or charybdotoxin, an inhibitor of large and
intermediate conductance Ca(2+)-activated K(+) channels, and it was significantly
inhibited by tetraethylammonium, a non-selective inhibitor of Ca(2+)-activated
K(+) channels and N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF
525a), a nonselective cytochrome P-450 monooxygenase (CYP) inhibitor, or
ketoconazole, a selective CYP3A inhibitor in only normal rabbits. These results
suggest that short-term hypercholesterolemia decreased EDHF-induced relaxation
mediated through K(+) channels in rabbit carotid artery and that it may be due
partially to the inhibition of CYP3A system in the carotid artery at an early
stage of hypercholesterolemia.
PMID- 17035096
TI - Effects of acute and prolonged naphthalene exposure on brain monoaminergic
neurotransmitters in rainbow trout (Oncorhynchus mykiss).
AB - We have shown previously that acute (1 to 6 h) and prolonged (1 to 5 days)
exposure of rainbow trout to naphthalene resulted in decreased plasmatic cortisol
and 17-beta-estradiol levels. In order to elucidate the mechanisms through which
naphthalene might disrupt endocrine regulation, the present study investigated
whether brain monoaminergic neurotransmitters are altered by the action of this
polycyclic aromatic hydrocarbon. In a first experiment, immature rainbow trout
were injected with vegetable oil alone or containing naphthalene (10 and 50
mg/kg, i.p.), and sacrificed 1, 3 and 6 h after treatment. In a second
experiment, slow-coconut oil implants alone or containing naphthalene (doses of
10 and 50 mg/kg) were i.p. located and fish sacrificed 1, 3 and 5 days after
treatment. Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC),
serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA) were
measured in several brain regions by HPLC. The results show that short-term
naphthalene increases DA and 5-HT contents in hypothalamus and telencephalon, but
differentially alter contents of the acid metabolites. Implants with naphthalene
reduced DA content in hypothalamus and preoptic region but increased in
telencephalon. 5-HT metabolism was decreased in hypothalamus, preoptic region,
pituitary and brain stem after 3 to 6 days of treatment. In addition, the levels
of NA were increased in hypothalamus and telencephalon after acute treatment and
in hypothalamus and preoptic area after several days of exposure to naphthalene.
These data suggest that brain neurotransmitter systems are sensitive to
polycyclic aromatic hydrocarbons and could represent a target of the naphthalene
induced neuroendocrine disruption.
PMID- 17035097
TI - The yeast genome may harbor hypoxia response elements (HRE).
AB - The hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor
activated when cells are submitted to hypoxia. The heterodimer is composed of two
subunits, HIF-1alpha and the constitutively expressed HIF-1beta. During normoxia,
HIF-1alpha is degraded by the 26S proteasome, but hypoxia causes HIF-1alpha to be
stabilized, enter the nucleus and bind to HIF-1beta, thus forming the active
complex. The complex then binds to the regulatory sequences of various genes
involved in physiological and pathological processes. The specific regulatory
sequence recognized by HIF-1 is the hypoxia response element (HRE) that has the
consensus sequence 5'BRCGTGVBBB3'. Although the basic transcriptional regulation
machinery is conserved between yeast and mammals, Saccharomyces cerevisiae does
not express HIF-1 subunits. However, we hypothesized that baker's yeast has a
protein analogous to HIF-1 which participates in the response to changes in
oxygen levels by binding to HRE sequences. In this study we screened the yeast
genome for HREs using probabilistic motif search tools. We described 24 yeast
genes containing motifs with high probability of being HREs (p-value<0.1) and
classified them according to biological function. Our results show that S.
cerevisiae may harbor HREs and indicate that a transcription factor analogous to
HIF-1 may exist in this organism.
PMID- 17035098
TI - Acclimatable cardiac and ventilatory responses to copper in the freshwater
crayfish Procambarus clarkii.
AB - Mortality and physiological tests following exposure to waterborne copper were
performed in the red swamp crayfish Procambarus clarkii from a central Italian
population. Mortality tests gave an estimated 96 h LC50 value (with 95%
confidence limits) of 162 (132-211) mg L(-1) waterborne copper II. Variations in
cardiac and ventilatory rates were simultaneously monitored using a non-invasive
plethysmographic technique. In experiments with different sub-lethal copper
concentrations (control, 0.5, 1 and 10 mg L(-1)) performed at different times (3,
6, 96 h), copper exposure elicited a reduction in both heart and scaphognatite
rates. Following exposure to 10 mg L(-1) copper for 96 h, the heart and
scaphognatite rates decreased to about 35% of the initial values. The reduction
was fully reversible, since crayfish exposed to 0.5, 1 and 10 mg Cu L(-1) for 96
h resumed control rates after a 3-h residence in clean water. In crayfish pre
exposed (96 h) to sub-lethal copper concentrations (0.1 and 1 mg L(-1)) and then
held in control water (3 h), the reduction of heart and scaphognatite rates after
exposure to 10 mg Cu L(-1) were significantly lower than in specimens pre-exposed
to control water. Therefore, copper induces a concentration and time dependent
reduction of both cardiac and ventilatory activity in P. clarkii; these responses
can be reduced or fully abolished by pre-exposure to sub-lethal levels of the
metal.
PMID- 17035099
TI - Antioxidant protection and plasma carotenoids of incubating great tits (Parus
major L.) in relation to health state and breeding conditions.
AB - Carotenoids are biologically active pigments, which are important for animals due
to their dual role in health maintenance and ornamental signalling. In adult
birds, immunostimulatory properties of carotenoids have been repeatedly
demonstrated while much less is known about the importance of carotenoids as
antioxidants. We studied the relationships between plasma carotenoid levels, as
well as total antioxidant protection, and various hemato-serological health state
indices in female great tits (Parus major L.), incubating their second clutches
in two contrasting (coniferous and deciduous) habitats in southwest Estonia. To
manipulate reproductive effort, four eggs were removed from half of the clutches
during laying to stimulate females to lay additional eggs. However, egg removal
had no effect on the final number of eggs laid. Plasma carotenoid levels
increased seasonally in parallel with caterpillar food availability. However, no
between-habitat differences in carotenoid levels, total antioxidant capacity, or
indices of health state could be found despite the apparently better feeding
conditions in the coniferous habitat. No correlation was detected between plasma
carotenoid levels and measures of total antioxidant capacity, which suggests that
at least for the adult birds feeding on naturally carotenoid-rich diet,
antioxidant function of carotenoids is not of primary importance. A strong non
linear association between the measures of antioxidant protection and leukocytic
markers of inflammation was found, which suggests that measures of total
antioxidant capacity deserve further attention in ecophysiological studies as
potential indicators of immunopathology.
PMID- 17035100
TI - Isolation and expression of zebrafish zinc-finger transcription factor gene tsh1.
AB - We report the expression patterns of tsh1, a zebrafish homologue of the
Drosophila homeotic gene teashirt. Expression of tsh1 is first detected at the 2
somite stage (10h post-fertilization, hpf) at the anterior end of the spinal
cord. Expression expands toward the posterior spinal cord, and by the prim-5
stage (24 hpf) tsh1 transcripts are detected throughout spinal cord. Between the
14- and 25-somite stage (16-24 hpf), spinal cord expression shows a clear
anterior boundary at the rostral margin of rhombomere 7. Around the prim-25 stage
(36 hpf), while the spinal expression of tsh1 decreases, new expression is
detected in the pectoral fin buds and dorsal forebrain. By the long-pec stage (48
hpf), spinal cord expression is undetectable, but strong expression is observed
in the rhombencephalon, telencephalon, tectum opticum, midbrain-hindbrain
boundary, in the first pharyngeal arch and in the eyes. This expression persists
at least until the larval stages. Retinoic acid signaling influences tsh1
expression. Zebrafish tsh1 expression was induced in the anterior neural tube in
embryos treated briefly with exogenous retinoic acid. Furthermore, tsh1
expression was down-regulated in the spinal cord in the zebrafish neckless mutant
in which RA signaling is disrupted due to a missense mutation in the gene
encoding retinaldehyde dehydrogenase type 2.
PMID- 17035101
TI - Dynamic expression of R-spondin family genes in mouse development.
AB - R-spondins (Rspo) are a recently discovered secretory protein family with four
members in human and mouse. We and others demonstrated that R-spondins can
activate canonical Wnt signaling and beta-catenin-dependent gene expression. Our
study further demonstrated that R-spondins are novel ligands for the Frizzled8
and LRP6 (LDL-receptor-related protein 6) receptors. To gain insight into their
biological functions, the RNA expression pattern of the mouse R-spondin family
genes was analyzed during mouse development. Our study shows that R-spondin gene
transcripts are widely expressed with distinct patterns in mouse at different
developmental stages.
PMID- 17035102
TI - Yeast Rev1 is cell cycle regulated, phosphorylated in response to DNA damage and
its binding to chromosomes is dependent upon MEC1.
AB - Translesion DNA synthesis (TLS) is one of the mechanisms involved in lesion
bypass during DNA replication. Three TLS polymerases (Pol) are present in the
yeast Saccharomyces cerevisiae: Pol zeta, Pol eta and the product of the REV1
gene. Rev1 is considered a deoxycytidyl transferase because it almost exclusively
inserts a C residue in front of the lesion. Even though REV1 is required for most
of the UV-induced and spontaneous mutagenesis events, the role of Rev1 is poorly
understood since its polymerase activity is often dispensable. Rev1 interacts
with several TLS polymerases in mammalian cells and may act as a platform in the
switching mechanism required to substitute a replicative polymerase with a TLS
polymerase at the sites of DNA lesions. Here we show that yeast Rev1 is a
phosphoprotein, and the level of this modification is cell cycle regulated under
normal growing conditions. Rev1 is unphosphorylated in G1, starts to be modified
while cells are passing S phase and it becomes hyper-phosphorylated in mitosis.
Rev1 is also hyper-phosphorylated in response to a variety of DNA damaging
agents, including treatment with a radiomimetic drug mostly causing double-strand
breaks (DSB). By using the chromosome spreading technique we found the Rev1 is
bound to chromosomes throughout the cell cycle, and its binding does not
significantly increase in response to genotoxic stress. Therefore, Rev1
phosphorylation does not appear to modulate its binding to chromosomes,
suggesting that such modification may influence other aspects of the TLS process.
Rev1 binding under damaged and undamaged conditions, is at least partially
dependent on MEC1, a gene playing a pivotal role in the DNA damage checkpoint
cascade. This genetic dependency may suggest a role for MEC1 in spontaneous
mutagenesis events, which require a functional REV1 gene.
PMID- 17035103
TI - Solid phase proteomics: dramatic reinforcement of very weak protein-protein
interactions.
AB - Very weak protein-protein interactions may play a critical role in cell
physiology but they are not easily detectable in "in vitro" experiments. To
detect these weak interactions, we have developed a strategy that included: (a)
design of a rapid and very effective crosslinking of protein-protein complexes
with poly-functional reagents; (b) selective adsorption of very large proteins on
lowly activated ionic exchangers, based on the need of a multipoint physical
adsorption to incorporate the proteins into the matrix; (c) purification by
selective adsorption of protein-protein complexes formed by strong protein
protein interactions, via selective adsorption of the complexes on lowly
activated ionic exchangers via multi-protein physical adsorption and leaving the
non-associated proteins in the solution; (d) reinforcement of very weak protein
protein interactions by selective adsorption of the complex on lowly activated
ionic exchange supports via a synergetic cooperation of the weak protein-protein
interaction plus the interactions of both proteins with the support enabling the
almost full shifting of the equilibrium towards the association position; (e)
control of the aggregation state of proteins like BSA, formed by weak protein
protein interactions. In this last case, it seems that the interaction of the
protein molecules placed on the borders of the aggregate with the groups on the
support partially stabilizes the whole aggregate, although, some molecules of the
aggregate cannot interact with the support. The size of the aggregates may be
defined by controlling the concentration of ionised groups on the support: the
less activated the supports are, the bigger the complexes. In this way, solid
phase proteomics could be a very interesting tool to detect weak protein-protein
interactions.
PMID- 17035104
TI - Detection of S-nitrosothiols in biological fluids: a comparison among the most
widely applied methodologies.
AB - Many different methodologies have been applied for the detection of S
nitrosothiols (RSNOs) in human biological fluids. One unsatisfactory outcome of
the last 14 years of research focused on this issue is that a general consensus
on reference values for physiological RSNO concentration in human blood is still
missing. Consequently, both RSNO physiological function and their role in disease
have not yet been clarified. Here, a summary of the values measured for RSNOs in
erythrocytes, plasma, and other biological fluids is provided, together with a
critical review of the most widely used analytical methods. Furthermore, some
possible methodological drawbacks, responsible for the highlighted discrepancies,
are evidenced.
PMID- 17035105
TI - A general method for the extraction of citrus leaf proteins and separation by 2D
electrophoresis: a follow up.
AB - With the aim of studying differentially expressed proteins as a function of
abiotic and biotic stress in citrus plants, we optimized a protocol for the
extraction of total leaf proteins and their 2-DE separation using commercially
available immobilized pH gradient strips (IPGs) in the first dimension. Critical
factors for good reproducibility of citrus leaf protein separation were
identified: trichloroacetic acid (TCA)/acetone precipitation after extraction in
lysis buffer, sample fractionation on narrow range overlapping IPGs and sample
cup loading at the anodic or cathodic end of the strip. The use of thiourea and a
strong detergent (C7BzO) in the solubilization/rehydration buffer, coupled with
the increase to 10% of SDS in the equilibration buffer before the second
dimension seemed to affect positively the resolution of basic proteins. Using our
protocol we resolved about 30 basic proteins on 6.3-8.3 pH range strips. Further,
our protocol was successfully applied reproducibly on the analysis of control and
salt exposed leaf samples of Citrus reshni Hort. Ex Tan.
PMID- 17035106
TI - Efficient and scalable method in isolation of polymethoxyflavones from orange
peel extract by supercritical fluid chromatography.
AB - Polymethoxyflavones (PMFs) from citrus genus are of particular interest because
of their broad spectrum of biological activities, such as anti-inflammatory, anti
carcinogenic, and anti-atherogenic properties. Recently, the exploration into the
beneficial health properties of PMFs in citrus fruits has dramatically increased.
However, the supply of pure PMFs in the in vivo study is a limiting factor due to
the difficulties in large-scale isolation of the interested PMFs. Therefore, the
development of an efficient and a scalable separation method of PMFs is necessary
and significant. In this paper, we report a newly developed method for efficient
and relatively large-scale isolation of four PMFs from sweet orange (Citrus
sinensis) peel by employing supercritical chromatography (SFC): nobiletin,
tangeretin, 3,5,6,7,8,3',4'-heptamethoxyflavone and 5,6,7,4'-tetramethoxyflavone.
PMID- 17035107
TI - Current methods for phosphoprotein isolation and enrichment.
AB - The phosphorylation of proteins is a central paradigm of signal transduction. The
substitution of neutral hydroxyl groups of serine, threonine and tyrosine with a
negatively charged phosphate group alters the physicochemical and immunogenic
properties of the protein, which then can be used to isolate these isoforms. In
the last decades several different techniques were applied, attempting to
selectively enrich protein populations with this post-translational modification.
This review aims to give an overview on the arsenal of available methods to
extract phosphoproteins focusing on chromatographic approaches.
PMID- 17035108
TI - Contribution of W229 to the transglycosylation activity of 4-alpha
glucanotransferase from Pyrococcus furiosus.
AB - A W229H mutant of 4-alpha-glucanotransferase (4-alpha-GTase) from Pyrococcus
furiosus was constructed and its catalytic properties were studied to investigate
the role of W229 in the catalytic specificities of the enzyme. Various activities
and kinetic parameters were determined for the wild-type and W229H mutant
enzymes. The transglycosylation factor and transglycosylation activity of the
mutant enzyme markedly decreased, but its hydrolysis activity was scarcely
affected. It was discovered that the k(cat)/K(m) value of transglycosylation
activity significantly decreased to about 15% of that of the wild type, while
k(cat)/K(m) value of hydrolysis activity changed little for the mutant enzyme.
The hydrophobicity of W229 was thought to be critical to the transglycosylation
activity of the enzyme based on the enzyme's modeled tertiary structures.
PMID- 17035109
TI - Protein processing and other modifications analyzed by diagonal peptide
chromatography.
AB - Diagonal peptide chromatography consists of two consecutive, identical peptide
separations with in between an enzymatic or chemical alteration of the side-chain
structure of selected peptides. Such selected and altered peptides acquire
different chromatographic properties thereby segregating from non-altered
peptides in a series of secondary peptide separations. Originally described by
Brown and Hartley in 1966, we have modified the technique such that it can be
used for higher throughput gel-free proteomics. Our technique is termed COmbined
FRActional DIagonal Chromatography (COFRADIC) and exploits evoked differences of
the hydrophobicity of peptides in reverse-phase liquid chromatography. One
important advantage of COFRADIC is its versatility: by changing the alteration
reaction, different classes of peptides are sorted and finally analyzed. We
previously published protocols and applications for separating methionyl,
cysteinyl, amino terminal and phosphorylated peptides. In this review, we assess
the potential of COFRADIC for the analysis of several posttranslational
modifications emphasizing on in vivo protein processing events. Additional
modifications that can be analyzed include phosphorylation and N-glycosylation.
The potential of COFRADIC for isolating peptides holding such modified amino
acids are discussed here.
PMID- 17035110
TI - GERD and interstitial lung disease. Cause, effect, or true true and unrelated?
PMID- 17035111
TI - Sexual dimorphism affects tibia size and shape but not tissue-level mechanical
properties.
AB - Understanding how growth influences adult bone morphology and tissue quality
should provide important insight into why females show a greater incidence of
stress fractures early in life and fragility fractures later in life compared to
males. The objective of this study was to test whether females acquire similar
tissue-level mechanical properties as males by the time peak bone properties are
established. Standardized beams of bone were machined from the tibial diaphyses
of 14 young, adult females ranging in age from 22 to 46 years. Data for males
(n=17, age=17-46 years) were taken from a prior study. Measures of tissue-level
mechanical properties, including stiffness, strength, ductility, toughness, and
damageability, were compared between sexes using t-tests. The relationship
between cross-sectional morphology and tissue-level mechanical properties was
also examined. Males and females showed nearly identical tissue-level mechanical
properties. Both sexes also showed similar age-related degradation of mechanical
properties and a similar relationship between cross-sectional morphology and
tissue quality. However, for all body sizes, female tibiae were smaller relative
to body size (i.e., less robust) compared to males. The results indicated that
sex-specific growth patterns affected transverse bone size, but did not affect
tissue-level mechanical properties. This, combined with the observation that
young, adult female long bones are undersized relative to body size, suggests
that adult females would be expected to accumulate more damage under intense
loading compared to males. This may be a contributing factor to the greater
incidence of stress fractures observed for female military recruits.
PMID- 17035114
TI - OP pesticides, organic diets, and children's health.
PMID- 17035117
TI - Allergies: the new lore of spores.
PMID- 17035115
TI - Prolactin changes as a consequence of chemical exposure.
PMID- 17035123
TI - NTP draft brief on DEHP.
PMID- 17035124
TI - A two-way street: building lasting community connections.
PMID- 17035126
TI - Caring for children amidst chaos: guidelines to maintain health.
PMID- 17035127
TI - Registering skepticism: does the EPA's pesticide review protect children?
PMID- 17035128
TI - Embryonic insight: mouse histology in 3-D.
PMID- 17035129
TI - Social ecology of children's vulnerability to environmental pollutants.
AB - BACKGROUND: The outcomes of exposure to neurotoxic chemicals early in life depend
on the properties of both the chemical and the host's environment. When our
questions focus on the toxicant, the environmental properties tend to be regarded
as marginal and designated as covariates or confounders. Such approaches blur the
reality of how the early environment establishes enduring biologic substrates.
OBJECTIVES: In this commentary, we describe another perspective, based on decades
of biopsychological research on animals, that shows how the early, even prenatal,
environment creates permanent changes in brain structure and chemistry and
behavior. Aspects of the early environment-encompassing enrichment, deprivation,
and maternal and neonatal stress-all help determine the functional responses
later in life that derive from the biologic substrate imparted by that
environment. Their effects then become biologically embedded. Human data,
particularly those connected to economically disadvantaged populations, yield
equivalent conclusions. DISCUSSION: In this commentary, we argue that treating
such environmental conditions as confounders is equivalent to defining genetic
differences as confounders, a tactic that laboratory research, such as that based
on transgenic manipulations, clearly rejects. The implications extend from
laboratory experiments that, implicitly, assume that the early environment can be
standardized to risk assessments based on epidemiologic investigations.
CONCLUSIONS: The biologic properties implanted by the early social environment
should be regarded as crucial elements of the translation from laboratory
research to human health and, in fact, should be incorporated into human health
research. The methods for doing so are not clearly defined and present many
challenges to investigators.
PMID- 17035130
TI - Stable isotopic tracing-a way forward for nanotechnology.
AB - Numerous publications and reports have expressed health and safety concerns about
the production and use of nanoparticles, especially in areas of exposure
monitoring, personal use, and environmental fate and transport. We suggest that
stable isotopic tracers, which have been used widely in the earth sciences and in
metabolic and other health-related studies for several decades, could be used to
address many of these issues. One such example we are pursuing is the use of
stable isotopes to monitor dermal absorption of zinc and titanium oxides in
sunscreen preparations and other personal care products. Other potential
applications of this tracing approach are discussed.
PMID- 17035131
TI - Ozone's impact on public health: contributions from indoor exposures to ozone and
products of ozone-initiated chemistry.
AB - OBJECTIVE: The associations between ozone concentrations measured outdoors and
both morbidity and mortality may be partially due to indoor exposures to ozone
and ozone-initiated oxidation products. In this article I examine the
contributions of such indoor exposures to overall ozone-related health effects by
extensive review of the literature as well as further analyses of published data.
FINDINGS: Daily inhalation intakes of indoor ozone (micrograms per day) are
estimated to be between 25 and 60% of total daily ozone intake. This is
especially noteworthy in light of recent work indicating little, if any,
threshold for ozone's impact on mortality. Additionally, the present study
estimates that average daily indoor intakes of ozone oxidation products are
roughly one-third to twice the indoor inhalation intake of ozone alone. Some of
these oxidation products are known or suspected to adversely affect human health
(e.g., formaldehyde, acrolein, hydroperoxides, fine and ultrafine particles).
Indirect evidence supports connections between morbidity/mortality and exposures
to indoor ozone and its oxidation products. For example, cities with stronger
associations between outdoor ozone and mortality tend to have residences that are
older and less likely to have central air conditioning, which implies greater
transport of ozone from outdoors to indoors. CONCLUSIONS: Indoor exposures to
ozone and its oxidation products can be reduced by filtering ozone from
ventilation air and limiting the indoor use of products and materials whose
emissions react with ozone. Such steps might be especially valuable in schools,
hospitals, and childcare centers in regions that routinely experience elevated
outdoor ozone concentrations.
PMID- 17035132
TI - Adrenocortical response to stress and thyroid hormone status in free-living
nestling white storks (Ciconia ciconia) exposed to heavy metal and arsenic
contamination.
AB - BACKGROUND/OBJECTIVE: Endocrine parameters have proven useful in the detection of
early or low-level responses to pollutants. Although most of the studies on
endocrine modulation have been focused on processes involving gonadal steroids,
contaminants may target other parts of the endocrine system as well. In this
study we examined the adrenocortical stress response and thyroid hormone status
in free-living nestling white storks (Ciconia ciconia) in relation to heavy
metals (zinc, lead, copper, cadmium) and arsenic levels in blood. METHODS:
Fieldwork was conducted in an area polluted by the Aznalcollar mine accident
(southwestern Spain) and in a reference site. We used a standardized capture,
handling, and restraint protocol to determine both baseline and maximum plasma
corticosterone. Circulating levels of thyroxine (T4) and triiodothyronine (T3)
were also measured. RESULTS: No effects of metals or As were found on baseline
corticosterone, but maximum levels of corticosterone were positively related to
Pb in both locations. This relationship was stronger in single nestlings than in
birds from multiple-chick broods, which suggests a greater impact of Pb on more
stressed individuals. Metal pollution did not affect plasma T4 or T3 levels,
although thyroid status differed with location. CONCLUSIONS: Because a
compromised hypothalamus-pituitary-adrenal (HPA) function can have far-reaching
consequences in terms of altered behavioral and metabolic processes necessary for
survival, our results suggest that birds exposed to sublethal Pb levels may be at
risk through an altered adrenocortical stress response, and further support the
idea that HPA axis-related end points might be useful indicators of metal
exposure and potential toxicity in wild animals.
PMID- 17035133
TI - Saxitoxin puffer fish poisoning in the United States, with the first report of
Pyrodinium bahamense as the putative toxin source.
AB - BACKGROUND: From January 2002 to May 2004, 28 puffer fish poisoning (PFP) cases
in Florida, New Jersey, Virginia, and New York were linked to the Indian River
Lagoon (IRL) in Florida. Saxitoxins (STXs) of unknown source were first
identified in fillet remnants from a New Jersey PFP case in 2002. METHODS: We
used the standard mouse bioassay (MBA), receptor binding assay (RBA), mouse
neuroblastoma cytotoxicity assay (MNCA), Ridascreen ELISA, MIST Alert assay,
HPLC, and liquid chromatography-mass spectrometry (LC-MS) to determine the
presence of STX, decarbamoyl STX (dc-STX), and N-sulfocarbamoyl (B1) toxin in
puffer fish tissues, clonal cultures, and natural bloom samples of Pyrodinium
bahamense from the IRL. RESULTS: We found STXs in 516 IRL southern (Sphoeroides
nephelus), checkered (Sphoeroides testudineus), and bandtail (Sphoeroides
spengleri) puffer fish. During 36 months of monitoring, we detected STXs in skin,
muscle, and viscera, with concentrations up to 22,104 microg STX equivalents
(eq)/100 g tissue (action level, 80 microg STX eq/100 g tissue) in ovaries.
Puffer fish tissues, clonal cultures, and natural bloom samples of P. bahamense
from the IRL tested toxic in the MBA, RBA, MNCA, Ridascreen ELISA, and MIST Alert
assay and positive for STX, dc-STX, and B1 toxin by HPLC and LC-MS. Skin mucus of
IRL southern puffer fish captive for 1-year was highly toxic compared to Florida
Gulf coast puffer fish. Therefore, we confirm puffer fish to be a hazardous
reservoir of STXs in Florida's marine waters and implicate the dinoflagellate P.
bahamense as the putative toxin source. CONCLUSIONS: Associated with fatal
paralytic shellfish poisoning (PSP) in the Pacific but not known to be toxic in
the western Atlantic, P. bahamense is an emerging public health threat. We
propose characterizing this food poisoning syndrome as saxitoxin puffer fish
poisoning (SPFP) to distinguish it from PFP, which is traditionally associated
with tetrodotoxin, and from PSP caused by STXs in shellfish.
PMID- 17035134
TI - Mortality and exposure response among 14,458 electrical capacitor manufacturing
workers exposed to polychlorinated biphenyls (PCBs).
AB - BACKGROUND: We expanded an existing cohort of workers (n = 2,588) considered
highly exposed to polychlorinated biphenyls (PCBs) at two capacitor manufacturing
plants to include all workers with at least 90 days of potential PCB exposure
during 1939-1977 (n = 14,458). Causes of death of a priori interest included
liver and rectal cancers, previously reported for the original cohort, and non
Hodgkin lymphoma (NHL), melanoma, and breast, brain, intestine, stomach, and
prostate cancers, based on other studies. METHODS: We ascertained vital status of
the workers through 1998, and cumulative PCB exposure was estimated using a new
job exposure matrix. Analyses employed standardized mortality ratios (SMRs; U.S.,
state, and county referents) and Poisson regression modeling. RESULTS: Mortality
from NHL, melanoma, and rectal, breast, and brain cancers were neither in excess
nor associated with cumulative exposure. Mortality was not elevated for liver
cancer [21 deaths; SMR 0.89; 95% confidence interval (CI), 0.55-1.36], but
increased with cumulative exposure (trend p-value = 0.071). Among men, stomach
cancer mortality was elevated (24 deaths; SMR 1.53; 95% CI, 0.98-2.28) and
increased with cumulative exposure (trend p-value = 0.039). Among women,
intestinal cancer mortality was elevated (67 deaths; SMR 1.31; 95% CI, 1.02
1.66), especially in higher cumulative exposure categories, but without a clear
trend. Prostate cancer mortality, which was not elevated (34 deaths; SMR 1.04;
95% CI, 0.72-1.45), increased with cumulative exposure (trend p-value = 0.0001).
CONCLUSIONS: This study corroborates previous studies showing increased liver
cancer mortality, but we cannot clearly associate rectal, stomach, and intestinal
cancers with PCB exposure. This is the first PCB cohort showing a strong exposure
response relationship for prostate cancer mortality.
PMID- 17035135
TI - Polybrominated diphenyl ether (PBDE) levels in an expanded market basket survey
of U.S. food and estimated PBDE dietary intake by age and sex.
AB - OBJECTIVES: Our objectives in this study were to expand a previously reported
U.S. market basket survey using a larger sample size and to estimate levels of
PBDE intake from food for the U.S. general population by sex and age. METHODS: We
measured concentrations of 13 polybrominated diphenyl ether (PBDE) congeners in
food in 62 food samples. In addition, we estimated levels of PBDE intake from
food for the U.S. general population by age (birth through > or = 60 years of
age) and sex. RESULTS: In food samples, concentrations of total PBDEs varied from
7.9 pg/g (parts per trillion) in milk to 3,726 pg/g in canned sardines. Fish were
highest in PBDEs (mean, 1,120 pg/g; median, 616 pg/g; range, 11.14-3,726 pg/g).
This was followed by meat (mean, 383 pg/g; median, 190 pg/g; range, 39-1,426
pg/g) and dairy products (mean, 116 pg/g; median, 32.2 pg/g; range, 7.9-683
pg/g). However, using estimates for food consumption (excluding nursing infants),
meat accounted for the highest U.S. dietary PBDE intake, followed by dairy and
fish, with almost equal contributions. Adult females had lower dietary intake of
PBDEs than did adult males, based on body weight. We estimated PBDE intake from
food to be 307 ng/kg/day for nursing infants and from 2 ng/kg/day at 2-5 years of
age for both males and females to 0.9 ng/kg/day in adult females. CONCLUSION:
Dietary exposure alone does not appear to account for the very high body burdens
measured. The indoor environment (dust, air) may play an important role in PBDE
body burdens in addition to food.
PMID- 17035136
TI - Cancer incidence among pesticide applicators exposed to dicamba in the
agricultural health study.
AB - BACKGROUND: Dicamba is an herbicide commonly applied to crops in the United
States and abroad. We evaluated cancer incidence among pesticide applicators
exposed to dicamba in the Agricultural Health Study, a prospective cohort of
licensed pesticide applicators in North Carolina and Iowa. METHODS: Detailed
pesticide exposure information was obtained through a self-administered
questionnaire completed from 1993 to 1997. Cancer incidence was followed through
31 December 2002 by linkage to state cancer registries. We used Poisson
regression to estimate rate ratios and 95% confidence intervals for cancer
subtypes by tertiles of dicamba exposure. Two dicamba exposure metrics were used:
lifetime exposure days and intensity-weighted lifetime exposure days (lifetime
days x intensity score). RESULTS: A total of 41,969 applicators were included in
the analysis, and 22,036 (52.5%) reported ever using dicamba. Exposure was not
associated with overall cancer incidence nor were there strong associations with
any specific type of cancer. When the reference group comprised low-exposed
applicators, we observed a positive trend in risk between lifetime exposure days
and lung cancer (p = 0.02), but none of the individual point estimates was
significantly elevated. We also observed significant trends of increasing risk
for colon cancer for both lifetime exposure days and intensity-weighted lifetime
days, although these results are largely due to elevated risk at the highest
exposure level. There was no apparent risk for non-Hodgkin lymphoma. CONCLUSIONS:
Although associations between exposure and lung and colon cancer were observed,
we did not find clear evidence for an association between dicamba exposure and
cancer risk.
PMID- 17035137
TI - Nitrate intake does not influence bladder cancer risk: the Netherlands cohort
study.
AB - OBJECTIVES: N-nitroso compounds, endogenously formed from nitrate-derived
nitrite, are suspected to be important bladder carcinogens. However, the
association between nitrate exposure from food or drinking water and bladder
cancer has not been substantially investigated in epidemiologic studies. METHODS:
We evaluated the associations between nitrate exposure and bladder cancer in the
Netherlands Cohort Study, conducted among 120,852 men and women, 55-69 years of
age at entry. Information on nitrate from diet was collected via a food frequency
questionnaire in 1986 and a database on nitrate content of foods. Individual
nitrate exposures from beverages prepared with tap water were calculated by
linking the postal code of individual residence at baseline to water company
data. After 9.3 years of follow-up and after excluding subjects with incomplete
or inconsistent dietary data, 889 cases and 4,441 subcohort members were
available for multivariate analyses. We calculated incidence rate ratios (RR) and
corresponding 95% confidence intervals (CIs) using Cox regression analyses. We
also evaluated possible effect modification of dietary intake of vitamins C and E
(low/high) and cigarette smoking (never/ever). RESULTS: The multivariate RRs for
nitrate exposure from food, drinking water, and estimated total nitrate exposure
were 1.06 (95% CI, 0.81-1.31), 1.06 (95% CI, 0.82-1.37), and 1.09 (95% CI, 0.84
1.42), respectively, comparing the highest to the lowest quintiles of intake.
Dietary intake of vitamins C and E (low/high) and cigarette smoking (never/ever)
had no significant impact on these results. CONCLUSION: Although the association
between nitrate exposure and bladder cancer risk is biologically plausible, our
results in this study do not support an association between nitrate exposure and
bladder cancer risk.
PMID- 17035138
TI - Public health impact of extremely low-frequency electromagnetic fields.
AB - INTRODUCTION: The association between exposure to extremely low-frequency
electric and magnetic fields (ELF) and childhood leukemia has led to the
classification of magnetic fields by the International Agency for Research on
Cancer as a "possible human carcinogen." This association is regarded as the
critical effect in risk assessment. Creating effective policy in light of
widespread exposure and the undisputed value of safe, reliable, and economic
electricity to society is difficult and requires estimates of the potential
public health impact and associated uncertainties. OBJECTIVES: Although a causal
relationship between magnetic fields and childhood leukemia has not been
established, we present estimates of the possible pubic health impact using
attributable fractions to provide a potentially useful input into policy analysis
under different scenarios. METHODS: Using ELF exposure distributions from various
countries and dose-response functions from two pooled analyses, we calculate
country-specific and worldwide estimates of attributable fractions (AFs) and
attributable cases. RESULTS: Even given a wide range of assumptions, we find that
the AF remains < 10%, with point estimates ranging from < 1% to about 4%. For
small countries with low exposure, the number of attributable cases is less than
one extra case per year. Worldwide the range is from 100 to 2,400 cases possibly
attributable to ELF exposure. CONCLUSION: The fraction of childhood leukemia
cases possibly attributable to ELF exposure across the globe appears to be small.
There remain, however, a number of uncertainties in these AF estimates,
particularly in the exposure distributions.
PMID- 17035139
TI - Blood lead levels and death from all causes, cardiovascular disease, and cancer:
results from the NHANES III mortality study.
AB - BACKGROUND: Analyses of mortality data for participants examined in 1976-1980 in
the second National Health and Nutrition Examination Survey (NHANES II) suggested
an increased risk of mortality at blood lead levels > 20 microg/dL. Blood lead
levels have decreased markedly since the late 1970s. In NHANES III, conducted
during 1988-1994, few adults had levels > 20 microg/dL. OBJECTIVE: Our objective
in this study was to determine the risk of mortality in relation to lower blood
lead levels observed for adult participants of NHANES III. METHODS: We analyzed
mortality information for 9,757 participants who had a blood lead measurement and
who were > or = 40 years of age at the baseline examination. Using blood lead
levels categorized as < 5, 5 to < 10, and > or = 10 microg/dL, we determined the
relative risk of mortality from all causes, cancer, and cardiovascular disease
through Cox proportional hazard regression analysis. RESULTS: Using blood lead
levels < 5 microg/dL as the referent, we determined that the relative risk of
mortality from all causes was 1.24 [95% confidence interval (CI), 1.05-1.48] for
those with blood levels of 5-9 microg/dL and 1.59 (95% CI, 1.28-1.98) for those
with blood levels > or = 10 microg/dL (p for trend < 0.001). The magnitude of
risk was similar for deaths due to cardiovascular disease and cancer, and tests
for trend were statistically significant (p < 0.01) for both causes of death.
CONCLUSION: In a nationally representative sample of the U.S. population, blood
lead levels as low as 5-9 mug/dL were associated with an increased risk of death
from all causes, cardiovascular disease, and cancer.
PMID- 17035140
TI - Organophosphate insecticides target the serotonergic system in developing rat
brain regions: disparate effects of diazinon and parathion at doses spanning the
threshold for cholinesterase inhibition.
AB - BACKGROUND: In the developing brain, serotonin (5HT) systems are among the most
sensitive to disruption by organophosphates. OBJECTIVES: We exposed neonatal rats
to daily doses of diazinon or parathion on postnatal days (PND)1-4 and evaluated
5HT receptors and the 5HT transporter in brainstem and forebrain on PND5,
focusing on doses of each agent below the maximum tolerated dose and spanning the
threshold for cholinesterase inhibition: 0.5, 1, or 2 mg/kg for diazinon, and
0.02, 0.05, and 0.1 mg/kg for parathion. RESULTS: Diazinon evoked up-regulation
of 5HT1A and 5HT2 receptor expression even at doses devoid of effects on
cholinesterase activity, a pattern similar to that seen earlier for another
organophosphate, chlorpyrifos. In contrast, parathion decreased 5HT1A receptors,
again at doses below those required for effects on cholinesterase. The two agents
also differed in their effects on the 5HT transporter. Diazinon evoked a decrease
in the brainstem and an increase in the forebrain, again similar to that seen for
chlorpyrifos; this pattern is typical of damage of nerve terminals and reactive
sprouting. Parathion had smaller, nonsignificant effects. CONCLUSIONS: Our
results buttress the idea that, in the developing brain, the various
organophosphates target specific neurotransmitter systems differently from each
other and without the requirement for cholinesterase inhibition, their supposed
common mechanism of action.
PMID- 17035142
TI - Persistence of symptoms in veterans of the First Gulf War: 5-year follow-up.
AB - BACKGROUND: During the 1990-1991 Gulf War, approximately 700,000 U.S. troops were
deployed to the Persian Gulf theater of operations. Of that number, approximately
100,000 have presented medical complaints through various registry and
examination programs. OBJECTIVES: Widespread symptomatic illness without defining
physical features has been reported among veterans of the 1991 Gulf War. We
ascertained changes in symptom status between an initial 1995 symptom evaluation
and a follow-up in 2000. METHODS: We assessed mailed symptom survey
questionnaires for 390 previously surveyed members of the U.S. Department of
Veterans Affairs Gulf War Registry for changes over the 5-year interval in terms
of number and severity of symptoms. RESULTS: For the cohort as a whole, we found
no significant changes in symptom number or severity. Those initially more
symptomatic in 1995 showed some improvement over time, but remained much more
highly symptomatic than those who had lesser initial symptomatology. CONCLUSIONS:
The symptom outbreak following the 1991 Gulf War has not abated over time in
registry veterans, suggesting substantial need for better understanding and care
for these veterans.
PMID- 17035141
TI - Neural tube defects and folate pathway genes: family-based association tests of
gene-gene and gene-environment interactions.
AB - BACKGROUND: Folate metabolism pathway genes have been examined for association
with neural tube defects (NTDs) because folic acid supplementation reduces the
risk of this debilitating birth defect. Most studies addressed these genes
individually, often with different populations providing conflicting results.
OBJECTIVES: Our study evaluates several folate pathway genes for association with
human NTDs, incorporating an environmental cofactor: maternal folate
supplementation. METHODS: In 304 Caucasian American NTD families with
myelomeningocele or anencephaly, we examined 28 polymorphisms in 11 genes: folate
receptor 1, folate receptor 2, solute carrier family 19 member 1, transcobalamin
II, methylenetetrahydrofolate dehydrogenase 1, serine hydroxymethyl-transferase
1, 5,10-methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate
homo-cysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine
methyltransferase reductase, betaine-homocysteine methyltransferase (BHMT), and
cystathionine-beta-synthase. RESULTS: Only single nucleotide polymorphisms (SNPs)
in BHMT were significantly associated in the overall data set; this significance
was strongest when mothers took folate-containing nutritional supplements before
conception. The BHMT SNP rs3733890 was more significant when the data were
stratified by preferential transmission of the MTHFR rs1801133 thermolabile T
allele from parent to offspring. Other SNPs in folate pathway genes were
marginally significant in some analyses when stratified by maternal
supplementation, MTHFR, or BHMT allele transmission. CONCLUSIONS: BHMT rs3733890
is significantly associated in our data set, whereas MTHFR rs1801133 is not a
major risk factor. Further investigation of folate and methionine cycle genes
will require extensive SNP genotyping and/or resequencing to identify novel
variants, inclusion of environmental factors, and investigation of gene-gene
interactions in large data sets.
PMID- 17035143
TI - A cancer risk assessment of inner-city teenagers living in New York City and Los
Angeles.
AB - BACKGROUND: The Toxics Exposure Assessment Columbia-Harvard (TEACH) project
assessed exposures and cancer risks from urban air pollutants in a population of
high school teenagers in New York City (NYC) and Los Angeles (LA). Forty-six high
school students participated in NYC and 41 in LA, most in two seasons in 1999 and
2000, respectively. METHODS: Personal, indoor home, and outdoor home 48-hr
samples of volatile organic compounds (VOCs), aldehydes, particulate matter with
aerodynamic diameter < or = 2.5 microm, and particle-bound elements were
collected. Individual cancer risks for 13 VOCs and 6 particle-bound elements were
calculated from personal concentrations and published cancer unit risks. RESULTS:
The median cumulative risk from personal VOC exposures for this sample of NYC
high school students was 666 per million and was greater than the risks from
ambient exposures by a factor of about 5. In the LA sample, median cancer risks
from VOC personal exposures were 486 per million, about a factor of 4 greater
than ambient exposure risks. The VOCs with the highest cancer risk included 1,4
dichlorobenzene, formaldehyde, chloroform, acetaldehyde, and benzene. Of these,
benzene had the greatest contributions from outdoor sources. All others had high
contributions from indoor sources. The cumulative risks from personal exposures
to the elements were an order of magnitude lower than cancer risks from VOC
exposures. CONCLUSIONS: Most VOCs had median upper-bound lifetime cancer risks
that exceeded the U.S. Environmental Protection Agency (EPA) benchmark of 1 x 10
6 and were generally greater than U.S. EPA modeled estimates, more so for
compounds with predominant indoor sources. Chromium, nickel, and arsenic had
median personal cancer risks above the U.S. EPA benchmark with exposures largely
from outdoors and other microenvironments. The U.S. EPA-modeled concentrations
tended to overestimate personal cancer risks for beryllium and chromium but
underestimate risks for nickel and arsenic.
PMID- 17035144
TI - Chlorinated pool attendance, atopy, and the risk of asthma during childhood.
AB - The pool chlorine hypothesis postulates that the rise in childhood asthma in the
developed world could result at least partly from the increasing exposure of
children to toxic gases and aerosols contaminating the air of indoor chlorinated
pools. To further assess this hypothesis, we explored the relationships between
childhood asthma, atopy, and cumulated pool attendance (CPA). We studied 341
schoolchildren 10-13 years of age who attended at a variable rate the same public
pool in Brussels (trichloramine in air, 0.3-0.5 mg/m3). Examination of the
children included a questionnaire, an exercise-induced bronchoconstriction (EIB)
test, and the measurement of exhaled nitric oxide (eNO) and total and
aeroallergen-specific serum IgE. CPA by children (range, 0-1,818 hr) emerged
among the most consistent predictors of asthma (doctor diagnosed or screened with
the EIB test) and of elevated eNO, ranking immediately after atopy and family
history of asthma or hay fever. Although the risk of elevated eNO increased with
CPA [odds ratio (OR) = 1.30; 95% confidence interval (CI), 1.10-1.43]
independently of total or specific serum IgE, the probability of developing
asthma increased with CPA only in children with serum IgE > 100 kIU/L (OR for
each 100-hr increase in CPA = 1.79; 95% CI, 1.07-2.72). All these effects were
dose related and most strongly linked to pool attendance before 6-7 years of age.
Use of indoor chlorinated pools especially by young children interacts with
atopic status to promote the development of childhood asthma. These findings
further support the hypothesis implicating pool chlorine in the rise of childhood
asthma in industrialized countries.
PMID- 17035145
TI - Reduction in asthma morbidity in children as a result of home remediation aimed
at moisture sources.
AB - OBJECTIVE: Home dampness and the presence of mold and allergens have been
associated with asthma morbidity. We examined changes in asthma morbidity in
children as a result of home remediation aimed at moisture sources. DESIGN: In
this prospective, randomized controlled trial, symptomatic, asthmatic children (n
= 62), 2-17 years of age, living in a home with indoor mold, received an asthma
intervention including an action plan, education, and individualized problem
solving. The remediation group also received household repairs, including
reduction of water infiltration, removal of water-damaged building materials, and
heating/ventilation/air-conditioning alterations. The control group received only
home cleaning information. We measured children's total and allergen-specific
serum immuno-globulin E, peripheral blood eosinophil counts, and urinary
cotinine. Environmental dust samples were analyzed for dust mite, cockroach,
rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year.
RESULTS: Children in both groups showed improvement in asthma symptomatic days
during the preremediation portion of the study. The remediation group had a
significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent
to treat) after remodeling, whereas these parameters in the control group did not
significantly change. In the postremediation period, the remediation group had a
lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29
vs. 11 of 33, respectively, p = 0. 003; intent to treat: 28.1% and 10.0%,
respectively, p = 0.11). CONCLUSION: Construction remediation aimed at the root
cause of moisture sources and combined with a medical/behavioral intervention
significantly reduces symptom days and health care use for asthmatic children who
live in homes with a documented mold problem.
PMID- 17035146
TI - Children show highest levels of polybrominated diphenyl ethers in a California
family of four: a case study.
AB - Polybrominated diphenyl ethers (PBDEs), a major class of flame retardants, are
ubiquitous environmental contaminants with particularly high concentrations in
humans from the United States. This study is a first attempt to report and
compare PBDE concentrations in blood drawn from a family. Serum samples from
family members collected at two sampling occasions 90 days apart were analyzed
for PBDE congeners. Concentrations of the lower-brominated PBDEs were similar at
the two sampling times for each family member, with children's levels 2- to 5
fold higher than those of their parents. Concentrations of, for example,
2,2',4,4'-tetrabromodiphenyl ether (BDE-47) varied from 32 ng/g lipid weight (lw)
in the father to 60, 137, and 245 ng/g lw in the mother, child, and toddler,
respectively. Decabromodiphenyl ether (BDE-209) concentrations differed
significantly between the two samplings. September concentrations in the father,
mother, child, and toddler were 23, 14, 143, and 233 ng/g lw, respectively.
December concentrations (duplicate results from the laboratory) were 2 and 3, 4
and 4, 9 and 12, and 19 and 26 ng/g lw, respectively. Parents' summation
operatorPBDE concentrations approached U.S. median concentrations, with
children's concentrations near the maximum (top 5%) found in U.S. adults. The
youngest child had the highest concentrations of all PBDE congeners, suggesting
that younger children are more exposed to PBDEs than are adults. Our estimates
indicate that house dust contributes to children's higher PBDE levels. BDE-209
levels for all family members were 10-fold lower at the second sampling. The
short half-life of BDE-209 (15 days) indicates that BDE-209 levels can decrease
rapidly in response to decreased exposures. This case study suggests that
children are at higher risk for PBDE exposures and, accordingly, face higher
risks of PBDE-related health effects than adults.
PMID- 17035147
TI - The economic impact of early life environmental tobacco smoke exposure: early
intervention for developmental delay.
AB - BACKGROUND AND OBJECTIVES: Early-life exposure to environmental tobacco smoke
(ETS) can result in developmental delay as well as childhood asthma and increased
risk of cancer. The high cost of childhood asthma related to ETS exposure has
been widely recognized; however, the economic impact of ETS-related developmental
delay has been less well understood. METHODS AND RESULTS: The Columbia Center for
Children's Environmental Health (CCCEH) has reported adverse effects of prenatal
ETS exposure on child development in a cohort of minority women and children in
New York City (odds ratio of developmental delay = 2.36; 95% confidence interval
1.22-4.58). Using the environmentally attributable fraction (EAF) approach, we
estimated the annual cost of one aspect of ETS-related developmental delay: Early
Intervention Services. The estimated cost of these services per year due to ETS
exposure is > Dollars 50 million per year for New York City Medicaid births and
Dollars 99 million per year for all New York City births. CONCLUSION: The high
annual cost of just one aspect of developmental delay due to prenatal exposure to
ETS provides further impetus for increased prevention efforts such as educational
programs to promote smoke-free homes, additional cigarette taxes, and subsidizing
of smoking cessation programs.
PMID- 17035148
TI - Agricultural pesticide use and hypospadias in eastern Arkansas.
AB - INTRODUCTION: We assessed the relationship between hypospadias and proximity to
agricultural pesticide applications using a GIS-based exposure method. METHODS:
We obtained information for 354 cases of hypospadias born between 1998 and 2002
in eastern Arkansas; 727 controls were selected from birth certificates. We
classified exposure on pounds of pesticides (estimated by crop type) applied or
persisting within 500 m of each subject's home during gestational weeks 6 to 16.
We restricted our analyses to 38 pesticides with some evidence of reproductive,
developmental, estrogenic, and/or antiandrogenic effects. We estimated timing of
pesticide applications using crop phenology and published records. RESULTS:
Gestational age at birth [odds ratio (OR) = 0.91; 95% confidence interval (CI),
0.83-0.99], parity (OR = 0.79; 95% CI, 0.65-0.95), and delaying prenatal care
until the third trimester (OR = 4.04; 95% CI, 1.46-11.23) were significantly
associated with hypospadias. Risk of hypospadias increased by 8% for every 0.05
pound increase in estimated exposure to diclofop-methyl use (OR = 1.08; 95% CI,
1.01-1.15). Pesticide applications in aggregate (OR = 0.82; 95% CI, 0.70-0.96)
and applications of alachlor (OR = 0.56; 95% CI, 0.35-0.89) and permethrin (OR =
0.37; 95% CI, 0.16-0.86) were negatively associated with hypospadias.
CONCLUSIONS: Except for diclofop-methyl, we did not find evidence that estimated
exposure to pesticides known to have reproductive, developmental, or endocrine
disrupting effects increases risk of hypospadias. Further research on the
potential effects of exposure to diclofop-methyl is recommended.
PMID- 17035149
TI - Age- and concentration-dependent elimination half-life of 2,3,7,8
tetrachlorodibenzo-p-dioxin in Seveso children.
AB - OBJECTIVE: Pharmacokinetic and statistical analyses are reported to elucidate key
variables affecting 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in
children and adolescents. DESIGN: We used blood concentrations to calculate TCDD
elimination half-life. Variables examined by statistical analysis include age,
latency from exposure, sex, TCDD concentration and quantity in the body, severity
of chloracne response, body mass index, and body fat mass. PARTICIPANTS: Blood
was collected from 1976 to 1993 from residents of Seveso, Italy, who were < 18
years of age at the time of a nearby trichlorophenol reactor explosion in July
1976. RESULTS: TCDD half-life in persons < 18 years of age averaged 1.6 years
while those > or =18 years of age averaged 3.2 years. Half-life is strongly
associated with age, showing a cohort average increase of 0.12 year half-life per
year of age or time since exposure. A significant concentration-dependency is
also identified, showing shorter half-lives for TCDD concentrations > 400 ppt for
children < 12 years of age and 700 ppt when including adults. Moderate
correlations are also observed between half-life and body mass index, body fat
mass, TCDD mass, and chloracne response. CONCLUSIONS: Children and adolescents
have shorter TCDD half-lives and a slower rate of increase in half-life than
adults, and this effect is augmented at higher body burdens. RELEVANCE: Modeling
of TCDD blood concentrations or body burden in humans should take into account
the markedly shorter elimination half-life observed in children and adolescents
and concentration-dependent effects observed in persons > 400-700 ppt.
PMID- 17035150
TI - An exploration of ethical issues in research in children's health and the
environment.
AB - The consideration of ethical issues relating to pediatric environmental health is
a recent phenomenon. Discussions of biomedical ethics, research on children, and
environmental health research have a longer history. In the late 1990s,
researchers at the Kennedy Krieger Institute in Baltimore, Maryland, undertook a
study to compare the effectiveness of several methods of reducing lead risk in
housing. In a preliminary finding in the case of Grimes v. Kennedy Krieger
Institute, Inc., a Maryland court questioned the ethics of performing research on
children when there is no prospect of direct benefit to those children and
whether parents can consent to such research. This case dramatically raised the
profile of ethical issues among the pediatric environmental health research
community. To broaden the discussion of these issues and in response to the
Kennedy-Krieger case, the Children's Environmental Health Network held a working
meeting on 5 and 6 March 2004 to explore this topic. The articles in this mini
monograph were prepared by the authors as a result of the workshop and represent
their opinions. This article is an introduction to the workshop and a summary of
the articles to follow.
PMID- 17035151
TI - Trials and tribulations of protecting children from environmental hazards.
AB - Society is increasingly aware of the profound impact that the environment has on
children's health. Not surprisingly, there is increasing public scrutiny about
children's exposures to environmental hazards, especially for disadvantaged
children. These trends underscore the ethical imperative to develop a framework
to protect children from environmental hazards. Such a framework must include
regulations to test new chemicals and other potential hazards before they are
marketed, a strategy to conduct research necessary to protect children from
persistent hazards that are widely dispersed in their environment, stronger
regulatory mechanisms to eliminate human exposures to recognized or suspected
toxicants, and guidelines about the ethical conduct of research and the role of
experimental trials that test the efficacy and safety of interventions to prevent
or ameliorate children's exposure to persistent toxicants or hazards that are
widely dispersed in their environment.
PMID- 17035152
TI - The politics of risk: a human rights paradigm for children's environmental health
research.
AB - A human rights paradigm for environmental health research makes explicit the
relationship between poor health and poverty, inequality, and social and
political marginalization, and it aims at civic problem solving. In so doing, it
incorporates support for community-based, participatory research and takes
seriously the social responsibilities of researchers. For these reasons, a human
rights approach may be better able than conventional bioethics to address the
unique issues that arise in the context of pediatric environmental health
research, particularly the place of environmental justice standards in research.
At the same time, as illustrated by disagreements over the ethics of research
into lead abatement methods, bringing a human rights paradigm to bear in the
context of environmental health research requires resolving important tensions at
its heart, particularly the inescapable tension between ethical ideals and
political realities.
PMID- 17035153
TI - Privacy and ethics in pediatric environmental health research-part I: genetic and
prenatal testing.
AB - The pressing need for empirically informed public policies aimed at understanding
and promoting children's health has challenged environmental scientists to modify
traditional research paradigms and reevaluate their roles and obligations toward
research participants. Methodologic approaches to children's environmental health
research raise ethical challenges for which federal regulations may provide
insufficient guidance. In this article I begin with a general discussion of
privacy concerns and informed consent within pediatric environmental health
research contexts. I then turn to specific ethical challenges associated with
research on genetic determinants of environmental risk, prenatal studies and
maternal privacy, and data causing inflicted insight or affecting the
informational rights of third parties.
PMID- 17035154
TI - Privacy and ethics in pediatric environmental health research-part II: protecting
families and communities.
AB - BACKGROUND: In pediatric environmental health research, information about family
members is often directly sought or indirectly obtained in the process of
identifying child risk factors and helping to tease apart and identify
interactions between genetic and environmental factors. However, federal
regulations governing human subjects research do not directly address ethical
issues associated with protections for family members who are not identified as
the primary "research participant." Ethical concerns related to family consent
and privacy become paramount as pediatric environmental health research
increasingly turns to questions of gene-environment interactions. OBJECTIVES: In
this article I identify issues arising from and potential solutions for the
privacy and informed consent challenges of pediatric environmental health
research intended to adequately protect the rights and welfare of children,
family members, and communities. DISCUSSION: I first discuss family members as
secondary research participants and then the specific ethical challenges of
longitudinal research on late-onset environmental effects and gene-environment
interactions. I conclude with a discussion of the confidentiality and social
risks of recruitment and data collection of research conducted within small or
unique communities, ethnic minority populations, and low-income families.
CONCLUSIONS: The responsible conduct of pediatric environmental health research
must be conceptualized as a goodness of fit between the specific research context
and the unique characteristics of subjects and other family stakeholders.
PMID- 17035155
TI - Supplementing the traditional institutional review board with an environmental
health and community review board.
AB - BACKGROUND: Community-based research often involves additional ethical, legal,
and social considerations beyond those of the specific individuals involved in
the study. The traditional institutional review board (IRB) typically focuses on
protecting the rights and ensuring the safety of the individuals involved. For
projects involving community members, IRBs should be more sensitive to issues
related to the broader community concerns. OBJECTIVES: The objective of this
article is to discuss the concept of community-based participatory research and
the shortcomings of the traditional IRBs in dealing with ethical issues
associated with broader community concerns such as implications for family
members, neighborhood groups, and local businesses. I examine the rationale and
benefits for expanding the roles and responsibilities of review boards related to
community-based issues. DISCUSSION: I propose the development of environmental
health and community review boards (EHCRBs) that combine the fundamental
responsibilities and ethical concept of the traditional review boards with an
expanded ethical construct of dignity, veracity, sustainability, and justice,
with an added emphasis on community. CONCLUSIONS: Only by acknowledging the needs
of and working with the community can we ensure ethically based and socially
responsible research. An EHCRB will allow researchers and community members to
more fully address their mutual interest in conducting scientific, ethical, and
socially responsible research.
PMID- 17035162
TI - Vitiligo treatment options: an evolving scenario.
AB - Sequential displays of several treatment options for vitiligo have been scanned
from the literature, and are presented here. A few of the medical modalities have
been resigned to history, whereas others have become customary in clinical
practice. There has also been a recent surge of interest in the surgical
treatment of this disease. Accordingly, this has been appraised and summarized.
Special attention has been given to prevalent medical modalities so that they may
be effectively utilized by those currently in practice.
PMID- 17035163
TI - Psychosocial stress impairs working memory at high loads: an association with
cortisol levels and memory retrieval.
AB - Stress and cortisol are known to impair memory retrieval of well-consolidated
declarative material. The effects of cortisol on memory retrieval may in
particular be due to glucocorticoid (GC) receptors in the hippocampus and
prefrontal cortex (PFC). Therefore, effects of stress and cortisol should be
observable on both hippocampal-dependent declarative memory retrieval and PFC
dependent working memory (WM). In the present study, it was tested whether
psychosocial stress would impair both WM and memory retrieval in 20 young healthy
men. In addition, the association between cortisol levels and cognitive
performance was assessed. It was found that stress impaired WM at high loads, but
not at low loads in a Sternberg paradigm. High cortisol levels at the time of
testing were associated with slow WM performance at high loads, and with impaired
recall of moderately emotional, but not of highly emotional paragraphs.
Furthermore, performance at high WM loads was associated with memory retrieval.
These data extend previous results of pharmacological studies in finding WM
impairments after acute stress at high workloads and cortisol-related retrieval
impairments.
PMID- 17035164
TI - Comparison of intramuscular and intradermal applications of hepatitis B vaccine
in hemodialysis patients.
AB - This study compared the application of intramuscular recombinant hepatitis B
vaccine in hemodialysis patients with the application of accelerated intradermal
recombinant hepatitis B vaccine, which can be applied with one-tenth of the
standard dose. Sixty seronegative patients for hepatitis B were randomly
separated into two groups. Twenty mug of the recombinant hepatitis B vaccine was
intramuscularly applied at 0-, 1-, 2-, and 6-month intervals to the first group
(32 cases). One more dose was applied at month 12 to those whose anti-HBs titers
remained below 100 mIU/mL at month 7. The same vaccine was intradermally applied
at 2 microg dose six times with one-month intervals to the second group (28
cases). Vaccine applications were continued in those whose anti-HBs titers
remained below 100 mIU/mL at month 7 until antibody titers reached above this
value or until the dose number became 12. Measurements of antibody titers were
repeated at month 13 in both groups. As a result, in the vaccination of
hemodialysis patients against hepatitis B, the accelerated ID application of
hepatitis B vaccine with a dose reduced to one-tenth is more cost-effective than
the standard dose vaccination schedules. Especially for hemodialysis patients,
the time has come for routine application of ID hepatitis B vaccine as an
alternative vaccination method.
PMID- 17035165
TI - The effects of caffeine ingestion on performance time, speed and power during a
laboratory-based 1 km cycling time-trial.
AB - There is little published data in relation to the effects of caffeine upon
cycling performance, speed and power in trained cyclists, especially during
cycling of approximately 60 s duration. To address this, eight trained cyclists
performed a 1 km time-trial on an electronically braked cycle ergometer under
three conditions: after ingestion of 5 mg x kg-1 caffeine, after ingestion of a
placebo, or a control condition. The three time-trials were performed in a
randomized order and performance time, mean speed, mean power and peak power were
determined. Caffeine ingestion resulted in improved performance time (caffeine
vs. placebo vs. control: 71.1 +/- 2.0 vs. 73.4 +/- 2.3 vs. 73.3 +/- 2.7 s; P =
0.02; mean +/- s). This change represented a 3.1% (95% confidence interval: 0.7
5.6) improvement compared with the placebo condition. Mean speed was also higher
in the caffeine than placebo and control conditions (caffeine vs. placebo vs.
control: 50.7 +/- 1.4 vs. 49.1 +/- 1.5 vs. 49.2 +/- 1.7 km x h-1; P = 0.0005).
Mean power increased after caffeine ingestion (caffeine vs. placebo vs. control:
523 +/- 43 vs. 505 +/- 46 vs. 504 +/- 38 W; P = 0.007). Peak power also increased
from 864 +/- 107 W (placebo) and 830 +/- 87 W (control) to 940 +/- 83 W after
caffeine ingestion (P = 0.027). These results provide support for previous
research that found improved performance after caffeine ingestion during short
duration high-intensity exercise. The magnitude of the improvements observed in
our study could be due to our use of sport-specific ergometry, a tablet form and
trained participants.
PMID- 17035166
TI - Sex differences in the onset of seasonal reproductive quiescence in hamsters.
AB - Day length is the primary cue used by many mammals to restrict reproduction to
favourable spring and summer months, but it is unknown for any mammal whether the
seasonal loss of fertility begins at the same time and occurs at the same rate in
females and males; nor it established whether the termination of mating behaviour
in males and females coincides with the loss of fertility. We speculated that
females, owing to their greater energetic investment in reproduction, are the
limiting sex in terminating offspring production in short days (SDs). Oestrous
cycles and production of young were monitored in Syrian hamsters (Mesocricetus
auratus) transferred from long days (LDs) to SDs. Females were mated to LD males
after three to eight weeks of SD treatment; in a parallel experiment, males
housed in SDs were mated to LD females. After five and eight weeks in SDs, at
least twice as many males as females were fertile. Both males and females
continued to copulate for several weeks after becoming infertile. The onset of
seasonal infertility occurs earlier in females than males and the decline in
fertility precedes the seasonal loss of mating behaviour in both sexes.
PMID- 17035167
TI - Mating trials validate the use of DNA barcoding to reveal cryptic speciation of a
marine bryozoan taxon.
AB - Despite increasing threats to the marine environment, only a fraction of the
biodiversity of the oceans has been described, owing in part to the widespread
occurrence of cryptic species. DNA-based barcoding through screening of an
orthologous reference gene has been proposed as a powerful tool to uncover
biological diversity in the face of dwindling taxonomic expertise and the
limitations of traditional species identification. Although DNA barcoding should
be particularly useful in the sea, given the prevalence of marine cryptic
species, the link between taxa identified through DNA barcodes and reproductively
isolated taxa (biological species) has rarely been explicitly tested. Here, we
use an integrated framework comparing breeding compatibility, morphology and
mitochondrial (cytochrome c oxidase 1) and nuclear (elongation factor-1-alpha)
DNA sequence variation among globally distributed samples of the cosmopolitan
marine bryozoan Celleporella hyalina (L.). Our results reveal that C. hyalina
comprises numerous deep, mostly allopatric, genetic lineages that are
reproductively isolated, yet share very similar morphology, indicating rampant
cryptic speciation. The close correspondence between genetic lineages and
reproductively isolated taxa in the context of minimal morphological change
suggests that DNA barcoding will play a leading role in uncovering the hidden
biodiversity of the oceans and that the sole use of morphologically based
taxonomy would grossly underestimate the number of marine species.
PMID- 17035168
TI - Copulation, genital damage and early death in Callosobruchus maculatus.
AB - Antagonistic sexual coevolution stems from the notion that male and female
interests over reproduction are in conflict. Such conflicts appear to be
particularly obvious when male genital armature inflicts damage to the female
reproductive tract resulting in reduced female longevity. However, studies of
mating frequency, genital damage and female longevity are difficult to interpret
because females not only sustain more genital damage, but also receive more
seminal fluid when they engage in multiple copulations. Here, we attempt to
disentangle the effects of genital damage and seminal fluid transfer on female
longevity in the beetle Callosobruchus maculatus (Coleoptera: Bruchidae). Males
copulating for the sixth time in succession inflicted greater levels of genital
damage, but transferred smaller ejaculates in comparison with virgin males. The
number of copulations performed by males was negatively related to female
fecundity and positively related to female longevity, suggesting a trade-off
between fecundity and longevity. However, inclusion of fecundity as a covariate
revealed sperm and/or seminal fluid transfer to have a negative impact on female
longevity above that caused by the fecundity-longevity trade-off. The
consequences of multiple copulations on female longevity were examined. Females
that mated twice laid more eggs and died sooner than those that mated once.
However, incorporation of fecundity as a covariate into our statistical model
removed the effect of female mating frequency on female longevity, indicating
that double-mated females suffer greater mortality owing to the trade-off between
fecundity and longevity. Males of this species are known to transfer very large
ejaculates (up to 8% of their body weight), which may represent a significant
nutritional benefit to females. However, the receipt of large ejaculates appears
to carry costs. Thus, the interpretation of multiple mating experiments on female
longevity and associated functional explanations of polyandry in this species are
likely to be complex.
PMID- 17035169
TI - Increased genetic diversity as a defence against parasites is undermined by
social parasites: Microdon mutabilis hoverflies infesting Formica lemani ant
colonies.
AB - Genetic diversity can benefit social insects by providing variability in immune
defences against parasites and pathogens. However, social parasites of ants
infest colonies and not individuals, and for them a different relationship
between genetic diversity and resistance may exist. Here, we investigate the
genetic variation, assessed using up to 12 microsatellite loci, of workers in 91
Formica lemani colonies in relation to their infestation by the specialist social
parasite Microdon mutabilis. At the main study site, workers in infested colonies
exhibited lower relatedness and higher estimated queen numbers, on average, than
uninfested ones. Additionally, estimated queen numbers were negatively correlated
with estimated average numbers of mates per queen within infested colonies. At
another site, infested colonies also exhibited significantly lower worker
relatedness, and estimated queen numbers were comparable in trend. In contrast,
in two populations of F. lemani where M. mutabilis was absent, relatedness within
colonies was high (40 and 90% with R>0.6). While high genetic variation can
benefit social insects by increasing their resistance to pathogens, there may be
a cost in the increased likelihood of infiltration by social parasites owing to
greater variation in nestmate recognition cues. This study provides the first
empirical test of this hypothesis.
PMID- 17035171
TI - Social scripts and stark realities: Kenyan adolescents' abortion discourse.
AB - This study explores students' narratives and discourses about adolescent
pregnancy and abortion elicited via internet-based open-ended questions posed in
response to a cartoon vignette. We report on content analysis of recommendations
and strategies for how to manage the unplanned pregnancy of a fictional young
couple and in their own personal lives. The responses of 614 young people were
analysed. Strategies vary widely. They include giving birth, adoption, running
away, abortion, denial, and postponement until discovery. Young people were also
queried about unplanned pregnancy resolution among their peers. Discourse
analysis reveals competing social scripts on abortion. Florid condemnation of
abortion acts in the hypothetical cases contrasts with more frank and sober
description of peers' real life abortion behaviour. Students' language is
compared with that found in official curricula. The rhetorical devices,
moralizing social scripts and dubious health claims about abortion in students'
online narratives mirror the tenor and content of their academic curricula as
well as Kenyan media presentation of the issue. The need for factual information,
dispassionate dialogue and improved contraceptive access is considerable.
PMID- 17035172
TI - Process and outcome study of multidisciplinary prosthetic treatment for
velopharyngeal dysfunction.
AB - BACKGROUND: A prosthetic approach to velopharyngeal dysfunction (VPD) is not new.
However, a collaborative interdisciplinary team approach by a speech-and-language
therapist, dental specialist and maxillofacial technician, including accurate
fitting using nasendoscopy, has provided an opportunity to define the clinical
care pathway, and audit the outcomes of this intervention. Systematic outcome
studies of the effectiveness of prosthetic appliances are few and largely
anecdotal. AIMS: The aim is twofold: first, to provide a description of the
process including diagnosis, clinical and technical fabrication; and second, to
determine the effectiveness of this intervention with nasendoscopy, objective
blind perceptual analysis of speech data and nasometry. METHODS & PROCEDURES: The
selection criteria, age, aetiology and process of fabrication are described.
Thirty-one patients embarked on the programme, but seven patients after initial
failure or refusal were re-entered into the programme for a second time resulting
in 38 interventions. At the time of audit, 20 patients had completed the
treatment, but four of these were inadequately documented. This study reports on
the 16 patients who successfully completed the programme and who had
comprehensive records. OUTCOMES & RESULTS: Significant differences were found
between the pre- and post-treatment evaluations on the speech parameters of
hypernasality, audible nasal emission and nasometry. CONCLUSIONS: In our centre
surgery is the first choice of treatment for VPD, but prosthetic management can
be a useful alternative when this is contraindicated, can be a useful temporary
solution and can be used to evaluate the potential benefits of surgical
intervention in some cases. This treatment requires the combined expertise of an
interdisciplinary team involving the speech-and-language therapist,
orthodontist/prosthodontist, maxillofacial technician and endoscopist.
PMID- 17035174
TI - [Study on the relationship between the resistance to MTX and the transport
protein superfamily of ATP-binding cassette that induces multiple drug
resistance].
AB - A major problem, especially the multidrug resistance, in chemotherapy was the
resistance to the chemotherapeutic agents. ATP-binding cassette transporter
superfamily that mediated the efflux of drugs was involved in multidrug
resistance. In order to understand the relationship between the resistance to MTX
and the transport protein superfamily of ATP-binding cassette, and to investigate
the mechanism of resistance to MTX, the study detected the expressions of mdr1,
mrp1, mrp2, mrp3, mrp5, mrp6 and abcg2 that encoded the transport proteins by
SuperArray analysis and the expressions of MRP1and MRP5 proteins by Western blot
analysis. The results showed that the multidrug resistance proteins were the
chief member of ATP-binding cassette transporter superfamily related to
resistance to MTX. And the high expression levels of mrp1 and mrp5 were detected.
Moreover, it revealed by SuperArray analysis that expression of mrp5 in MTX
resistant cells was significantly higher than that in normal mouse cells.
Besides, corresponding excessive expression of MRP5 protein in MTX-resistant
cells was also confirmed by Western blot. So, MRP5 could play important roles in
the resistance to MTX and would be a new potential drug target.
PMID- 17035175
TI - [Detecting of mtDNA mutations at position A3243G and G3316A in patients with type
2 diabetes mellitus in Wenzhou].
AB - To investigate the frequencies of mitochondria DNA (mtDNA) tRNA(Leu (UUR)) point
mutation A3243G and NADH dehydronase subunit 1(ND1) gene point mutation G3316A in
Wenzhou area of Zhejiang Province, and to explore the correlation between these
mutations and the clinical manifestations in patients with type 2 mellitus
diabetes(T2DM). Two hundreds and forty-four unrelated patients with T2DM and 156
healthy subjects without family history of T2DM were enrolled in Wenzhou area in
this study and screened for the point mutations mentioned above with polymerase
chain reaction (PCR) and restricted fragment length polymorphism(RFLP) analysis.
The heterogeneous mutations were confirmed with DNA sequencing and denaturing
high performance liquid chromatography (DHPLC) following T-A cloning of PCR
products. The percentage of A3243G mutation in group of patients with T2DM and
control were 0.410% and 0.0% (1/244 vs 0/156), respectively; however, there's not
any significant difference between these two groups in frequency of A3243G
mutation (P>0.05). G3316A mutation was detected in 4 of 244 cases with T2DM
(1.639%) and 2 of 156 healthy controls (1.282%), showing that there's also no
statistic difference between these two groups in frequency of G3316A mutation
(P>0.05). It's shown that the frequency of mtDNA tRNA(Leu (UUR)) A3243G mutation
is fairly low in patients with T2DM in Wenzhou area. Thus it's reasonable to
assume that this mutation may not be involved in the development and progression
of T2DM. Furthermore, it's demonstrated that the rate of G3316A mutation of mtDNA
ND1 gene is rare in patients with T2DM in Wenzhou area and this mutation also
happened in healthy control. It's suggested that G3316A mutation is just a gene
polymorphism of mtDNA and not related to the pathogenesis of T2DM.
PMID- 17035176
TI - [Identification of nine novel alternative splicing isoforms of RHD mRNA].
AB - To investigate the gene structures of RHD mRNA alternative splicing isoforms,
total RNA was extracted from normal cord blood samples and RHD mRNA were detected
using reverse transcription and polymerase chain reaction (RT-PCR) method. The
PCR products were cloned and directly sequenced. The splicing signals of various
isoforms were also analyzed by sequencing of exon-intron boundaries using RHD
gene specific primers, and the expressed sequence tags (ESTs) databank was
screened to find out other RHD alternative splicing isoforms. Nine novel and
three recurrent RHD alternative splicing isoforms were identified, among which
six isoforms were RHD-RHCE hybrid genes. Three types of alternative splicing were
found including exon skipping, alternative 5' splice sites and alternative 3'
splice sites. Exons 2 to 9 were involved in RHD mRNA alternative splicing. Two
other isoforms of intron retention type were also found in human ESTs databank.
Thus, the mRNA splicing mechanism of RHD gene was very complex, and nine novel
alternative splicing isoforms were identified including several isoforms based on
homologous RHD-RHCE hybrid gene.
PMID- 17035177
TI - [Polymorphism of CGG repeats in the FRAXE fragile site in the Qinba Mountain area
children and its association with intelligence].
AB - Variations of CGG repeats in the FRAXE fragile site were determined by PCR
amplification followed by polyacrylamide gel electrophoresis and sequencing in
randomly collected Qinba Mountain Area children whose intelligence level was
determined by China-Wechsler Intelligence Scale for Children (C-WISC).
Correlations between IQ score and the number of CGG repeats were analyzed.
Results indicated a difference in the range of CGG repeats among populations from
different regions, but no difference in the distribution of allele frequency in
such a population. CGG repeats were not associated with IQ scores in randomly
collected subjects (r=0.083, P>0.05), in males and females (r(m)=0.225, r(f)=
0.041, P>0.05), or in subjects with different intelligent levels (F=0.195,
P>0.05). It can be inferred that variation in the size of CGG repeats was not
associated with intellectual performance in the Qinba Mountain area children.
PMID- 17035178
TI - [Relationship between MC4R gene polymorphyism and body weight trait in beagle
dogs].
AB - The relationship between MC4R gene polymorphism and body weight in beagle dogs
was analyzed. Using gene-specific primers based on canine MC4R exonic sequences a
gene fragment was PCR amplified, cloned and sequenced to identify potential
polymorphisms. The relationship between a MC4R gene polymorphism detected by PCR
RFLP and canine body weight was analyzed. Three variants were found in beagle dog
MC4R DNA sequence, of which two were deletions and one was a transversion which
created a PshA I site that could be detected by PCR-RFLP. A statistically
significant relationship between this polymorphism and body weight was found.
MC4R gene could be a candidate modifier gene for canine body weight.
PMID- 17035179
TI - [The degree of inbreeding in 10 Chinese indigenous pig breeds].
AB - The population inbreeding coefficients of 10 indigenous pig breeds were estimated
by microsatellite markers. Results showed that: the inbreeding coefficient of
Guizhou miniature pig was the highest (0.1992), and that of Hanzhong black pig
the lowest (0.0727) among random mating populations. F test showed no significant
difference in inbreeding coefficient among the 8 breeds (P >0.05). The inbreeding
coefficient of the Guizhou miniature pig and Bama miniature pig inbreeding lines
was 0.5907 and 0.4761, respectively.
PMID- 17035180
TI - [Investigation on bovine leukocyte adhesion deficiency].
AB - Bovine leukocyte adhesion deficiency (BLAD) is autosomal recessive disease. The
pathogeny of BLAD is genic mutation of CD18-integrins on the leukocyte. In order
to know the carrier and occurrence of bovine leukocyte adhesion deficiency (BLAD)
among cows age from one to six years old in China, 1,000 cows were investigated
by means of amplifying a CD18 gene fragment via reverse transcriptase-PCR
followed by restriction digestion with Taq I. Results showed that 19 cows were
BLAD carriers, indicating that the BLAD carrier rate was 1.9 percent. In
addition, one cow was found to have BLAD.
PMID- 17035181
TI - [A molecular phylogeny of Shennongjia white bear based on mitochondrial
cytochrome b gene sequence].
AB - The phylogenetic relationship of Shennongjia white bear has been an open
question. Total DNA was extracted and sequenced from hair and feces of
Shennongjia white bear. Based on the partial Cyt b gene sequence obtained from
the samples, the authors aligned them using the Clustal W software program. The
MEGA software was used to analyze the divergences and base substitutions of the
partial Cyt b gene among the 11 species: Shennongjia white bear, Selenarctos
thibetanus, Euarctos americanus, Helarctos malayanus, Ursus arctos, Thalarctos
maritimus, Melursus ursinus, Procyon lotor, Ailuropoda melanoleuca, Ailurus
fulgens and Tremarctos ornatus. The phylogenetic trees constructed by multiple
methods (NJ and MP) supported nearly the same topology. Our molecular results
show that the sequence divergence between Shennongjia white bear and Asiatic
black bear (Selenarctos thibetanus) is lower than that between other species.
PMID- 17035182
TI - [Screening of peafowl microsatellite primers and analysis of genetic diversity].
AB - The applicability of chicken microsatellite primers to peafowl population was
analyzed in the present paper, and the results showed 14 of 29 pairs of
microsatellite primers from chicken could amplify peafowl DNA and produce
specific allele patterns. A mean of 1.71 alleles was found for each locus. Seven
pairs were highly polymorphic, and MCW0080 and MCW0098 were ideal markers for
peafowl. Genetic diversity analysis within and between the green peafowl and the
blue peafowl populations demonstrated that the expected heterozygosity of two
peafowl populations were 0.2482 and 0.2744, respectively. The inbreeding index
(FST), Reynolds' genetic distance and gene flow between the two populations were
0.078, 0.0603 and 3.896 respectively. These results indicate that the
heterozygosity and the genetic diversity of these two peafowl populations were
very low, and suggest a tendency towards intermixing.
PMID- 17035183
TI - [A research on Ig heavy chain constant region of five Acipenseridae].
AB - Analyzed the immunoglobulin (Ig) heavy chain constant regions of Russian sturgeon
(A. gueldenstaedtii); Sterlte sturgeon (A. ruthenus); Amur sturgeon (A.
schrenckii); Chinese sturgeon (A. sinensis) and Great sturgeon (Huso huso) with
molecular biology and bioinformatics methods. We cloned IgH nucleic acid
sequences by RT-PCR using the specific primer, then determined the
characteristics and functions of the amino acid sequences and plotted out the
sequence into four sub-regions (CH1-CH4), of which CH4 sub-regions one another
had the highest identity. According to the analysis of the variation expectation
value (Kaa), species differentiation time (T) in the CH4 sub-region phylogenetic
tree, we found that Chinese sturgeon and the theoretical common ancestor of the
other five sturgeon form the first bifurcation of the tree, while, among the five
left, Amur sturgeon and Huso sturgeon, Russian sturgeon and Siberian sturgeon,
Siberian sturgeon (sequence from GenBank), Sterlte itself form another three
bifurcations respectively. This result can clearly explain the relations of
taxonomic status, geographical distribution and evolution among the species
studied.
PMID- 17035184
TI - [Identification of a common deletion in different curly mutants in Drosophila
melanogaster].
AB - Curly is a easily distinguishable dominant mutant wing character. The Cy mutation
is the most commonly used dominant marker for the second chromosome balancers in
Drosophila melanogaster, but little is known about the Cy gene. Based on known
genomic and cytogenetic information, a 102 bp deletion which is located between
the Genes synaptotagmin (syt) and Activin Like Protein at 23B(Alp23B) on the
Drosophila melanogaster genome (release 4) had been found to be commonly
contained on Cy chromosome in three different curly strains. Meanwhile, when
using the deletion as a DNA marker, the result suggested that Cy homozygote be
lethal in embryo period. These results will provide some helpful information to
investigate molecular mechanism of curly wings in the further study.
PMID- 17035185
TI - [Genetic analysis of two extremely segregation distorted populations in rice
(Oryza sativa L.)].
AB - Segregation distortion is a quite common phenomenon in living species and thought
to be a potent evolutional force. The main reasons of distorted segregation
ratios are responsible for the selection of gametes or sporophytes. In this
study, two extreme segregation distortions from the progenies of lmi x 02428 and
d6 x 93-11 were identified. The segregation ratio of molecular markers tightly
linked with LMI and D6 genes were analyzed and skew segregation were found in the
markers tested which were indicated by significant deviation from the expected
Mendelian segregation ratio(1:2:1). The segregation distorted regions were
detected between molecular markers ST8 and ST8-2 near the centromere of
chromosome 8, and ST7-1 and ST7-3 near telomere of chromosome 7, respectively.
Meanwhile, the results indicated that segregation distortion had related with the
different crossed combinations.
PMID- 17035186
TI - [Sequence variation of chloroplast gene infA-rpl36 region occurred in some
Triticeae species].
AB - Based on the sequenced wheat chloroplast genome (cpDNA), a pair of primers in
infA-rp136 region was designed and used to amplify DNA from 12 diploid or
polyploid Triticeae species. The 12 PCR products were cloned and sequenced. The
resulting sequences ranged from 584 to 601 bp. DNA sequence analysis revealed
that variation was higher in their intergenic regions than in their coding
regions. Among these 12 species, the DNA sequence of coding region of infA gene
showed homology as high as 97 percent, indicating that the infA gene is highly
conserved among species. However, substantial deletions and insertions were found
in 5 out of 12 deduced amino acid sequences, confirming that infA is one of the
most evolutionally active cpDNA genes. Whereas the low variation was observed in
rp136 gene, implying that the different genes has different evolutionary speed.
The constructed phylogenetic trees demonstrate that the polyploidy species
Thinopyrum intermedium might have different origin of cytoplasm, and their
cytoplasm origins are as complex as their nuclear genome origins.
PMID- 17035187
TI - [Genetic analysis of a specially long pod character in artificially resythesized
Brassica napus L].
AB - Two hybrid combinations were made with a resynthesized specially-long pod line in
H218 Brassica napus L., namely H218 x Zhongyou 821, H218 x MSP334 and their six
generations F(1), F(2), backcrosses B(1) and B(2) and their parents P(1) and P(2)
were used to study the inheritance of 3 pod related traits, namely the full pod
length, the pod body length and the pod beak length. The results were the
followings: the three traits in the F(2) population of the two combinations had a
continuous normal distribution, indicating that these traits were quantitative in
nature and controlled by polygenes. The broad-sense heritabilities of the full
pod length, pod body length and pod beak length of the two combinations were
65.89%-70.77%, 60.14%-63.38% and 26.36%-46.44%, respectively. The narrow-sense
heritabilities were 44.01%-46.78%, 46.89%-47.38% and 18.08%-37.87%, respectively.
The results from the two combinations consistently showed that full pod length,
pod body length and pod beak length were controlled by 5, 6 and 2 genes
respectively. The preliminary study on the gene effect demonstrated that the
three traits in the two combinations all fit the additive-dominant model and the
epistatic effect was significant. The additive effects and the dominant effects
of the three traits in the two combinations were both significant. Of the full
pod length and the pod body length, the dominant effect was more significant than
the additive effect; and it is the same case for the pod beak length.
PMID- 17035188
TI - [RNA fingerprinting of the differential expression fragments related to
cytoplasmic male sterility in Chinese cabbage].
AB - In order to investigate the differential expression of the genes related to
cytoplasmic male sterility in Chinese cabbage (Brassica campestris L. ssp.
Penkinsis), a modified RNA fingerprinting technique was developed to compare the
difference in the total RNA from flower bud of Chinese cabbage among cytoplasmic
male sterility (CMS) lines, maintainer lines and F1 hybrids. Four stably
differential fragments S47-412, S93-622, S176-343 and S199-904 were amplified,
cloned and sequenced with primers selected from 186 random primers. Based on the
nucleotide sequence of the four differential fragments, four pairs of specific
primers were designed to validate the differential fragments. The validation
showed S47-412 and S93-622 were false positives and S176-343 and S199-904 were
confirmed by PCR with the specific primers. Sequence analysis revealed that both
of two differential fragments had strong homology with the nucleotide sequence of
orf224/atp6 site of Polima CMS and the nucleotide sequence of S176-343 and S199
904 had a superposed region. All these indicate that the two fragments probably
have strong relationship with cytoplasmic male sterility in Chinese cabbage.
PMID- 17035189
TI - [Cloning and diversity analysis of microorganism genes from alkalescence soil].
AB - The metagenomic DNAs were extracted and purified from alkalescence environmental
samples directly. On the basis of the metagenomic DNA, the alkaline soil 16S rDNA
library composed of 5,562 positive clones was constructed. The phylogenic tree
indicated that the bacteria from the alkaline soils were bio-diversity. The
metagenomic DNA library named AL01 was constructed by inserting restriction
fragments of the purified DNAs into plasmids pGEM-3Zf(+) vector. This library
contained 23,650 positive clones and the average foreign DNA fragments were about
3.2 kb. The length of the library covered 75.68 Mb. The efficiency of the
metagenomic library was approximately 6,000 clones from 1g dry soil samples.
After screening AL01 DNA library with the screening tactics of enzymes, we
confirmed that a positive clone, designated pGXAA2011, contained an alkaline
protease gene AP01. Enzymatic analysis proved that its reaction optimum pH was
9.5 and the optimum temperature was 40 degrees C. Furthermore, a clone,
designated pGXAG142 was screened from metagenomic DNA library, which expresses
beta-glucosidase. DNA sequence indicated that the potential ORF of pGXAG142,
which was named unglu01, there was no DNA or amino acids identity with the known
beta-glucosidase genes in the Genbank. The integrated ORF was cloned into pETBlue
2 vector and was then transformed into Tuner(DE3)pLacI. The recombinant
expression clone could express beta-glucosidase on the screening plate clearly
and the analysis of SDS-PAGE indicated that the target protein was about 29 kDa.
PMID- 17035190
TI - [Identification of the gene correlated with salt stress in the Saccharomyces
cerevisiae 263-H9 mutant].
AB - The mutant 263-H9 with hypersensitivity to several stress conditions (1.5 mol/L
Sorbitol, 0.65 mol/L NaCl and 15 degrees C) was obtained by using transposon
mutagenesis in the Saccharomyces cerevisiae strain W303-1A. Unlike other mutants
the transposon in 263-H9 was intergenic between GIP2 and YER053C-A. Using gene
knockout, a yeast genomic library and other methods, the gene correlated with the
salt stress response was identified. The data indicated that the phenotype of 263
H9 was not directly caused by the insertion of the transposon. On the other hand,
the hypersensitivity to salt and other stress conditions was due to the deletion
of 5 base pairs close to position 936 bp in the PBS2 gene essential for HOG
signal pathway regulation under salt stress.
PMID- 17035191
TI - [A novel method of the genome-wide prediction for the target genes and its
application].
AB - Based on the protein databases of several model species, this study developed a
new method of the Genome-wide prediction for the target genes, using Hidden
Markov model by Perl programming. The advantages of this method are high
throughput, high quality and easy prediction, especially in the case of multi
domains proteins families. By this method, we predicted the PPR and TPR proteins
families in whole genome of several model species. There were 536 PPR proteins
and 199 TPR proteins in Oryza sativa ssp. japonica, 519 PPR proteins and 177 TPR
proteins in Oryza sativa L. ssp. indica, 735 PPR proteins and 292 TPR proteins in
Arabidopsis thaliana, 6 PPR proteins and 32 TPR proteins in Cyanidioschyzon
merolae. Synechococcus and Thermophilic archaebacterium did not have PPR
proteins. By contrast, 10 TPR proteins were found in Synechococcus and 4 TPR
proteins were found in Thermophilic archaebacterium. Moreover, of these results,
some further bioinformatics analyses were conducted.
PMID- 17035192
TI - [Studies of methods and exploitation of computer software for mapping interactive
genes].
AB - There are six possible types of gene interaction in qualitative traits, namely,
complementary, duplicate, cumulative, dominant epistasis, recessive epistasis and
inhibiting. In genetic studies, the problem of mapping interactive genes may be
met sometimes, but no systematic researches on the methodology and computer
software for the mapping of interactive genes have been reported up to date. In
this paper, methods for the mapping of interactive genes based on maximum
likelihood estimation and corresponding computer software (IGMapping 1.0) are
presented. Computer simulations have shown that the methods proposed can
unbiasedly estimate the recombination frequency or linkage distance between a
codominant marker and an interactive gene.
PMID- 17035193
TI - [Research advances in expression profiling of mitochondrial proteins].
AB - As an important subcellular organelle, the mitochondrion plays an important role
in many physiological and pathological processes. This article reviews the most
recent studies in the significance, technological aspects, problems and future
prospects of expression profiling of mitochondrial proteins.
PMID- 17035194
TI - [Research progress on X chromosome STR loci in forensic medicine].
AB - This article summarizes the structure and hereditary characteristics of X
chromosome, research progress of using multiplex PCR system to amplify X
chromosome specific short tandom repeat (X-STR) loci and its forensic
applications. It also presents the advantages and disadvantages of X-STR loci in
the practice of forensic medicine, with an aim to promote wider use of X-STR loci
in forensic science.
PMID- 17035195
TI - [Progress in research of chitosan as a non-viral gene delivery vector].
AB - Efficiency of non-viral gene delivery based on chitosan and chitosan derivatives
as DNA condensing carrier is dependent on a series of factors, such as complex
size, the charge ratio of chitosan/DNA, molecular mass of chitosan, the degree of
chitosan deacetylation, pH and serum concentration of the transfection medium.
Through modifying the chitosan in a certain extent, we can change the efficiency
of transfection. Studies on transfection condition, efficiency and mechanism
using chitosan and chitosan derivatives as transfection agents are reviewed.
PMID- 17035196
TI - [Application of laser capture microdissection in plant genomic research].
AB - To a large degree, the growth and development of plants depend on the organ
and/or cell type-specific expression of genes. However, it can be difficult to
obtain sufficient number of specific cells from any developmental stage to
analyze expression of genes. Laser capture microdissection (LCM) is a novel
technique that allows us to collect pure targeted cell subgroup or even a single
cell quickly and precisely, thus the problem of tissue heterogeneity in molecular
analysis can be resolved successfully. In this paper, the principles of LCM were
introduced and the application of LCM in plant was summarized in gene expression
analysis, proteomics and plant-microbe interaction. Meanwhile, possible
directions of LCM in plant were put forward.
PMID- 17035197
TI - [Polyketides obtained using metagenome library technique].
AB - Polyketides are an important class of bioactive secondary metabolites. Since the
recurrence of the known polyketides is very high during the discovery of novel
natural polyketide compounds using traditional methods, new approaches are
developed for the biosynthesis of these compounds. This review discusses
discovery of new polyketides via metagenome library technique.
PMID- 17035198
TI - [The function of F-box protein in plant growth and development].
AB - Ubiquitin-mediated proteolysis is involved in many biological processes in
eukaryotes. SCF complex is a very important ubiquitin E3 ligase which has been
exploited very well in plants. F-box protein characterized by an F-box motif is a
subunit of SCF complex, which works as determinant in substrate recognition.
Currently, many F-box proteins have been identified in plants which are involving
in hormone (e.g., ethylene, auxin, gibberellin and jasmonate ) signal
transduction and biological processes, such as self-incompatibility and floral
development. F-box proteins may also participate stress response in plants.
Recent study suggested that the Arabidopsis F-box protein TIR1 is an auxin
receptor. Therefore, F-box protein mediated proteolysis may be an important gene
expression mechanism in plants.
PMID- 17035199
TI - Whither veterinary education--have we lost our direction?
PMID- 17035200
TI - Faculty development: principles and practices.
AB - Instructors in the health professions today must acquire knowledge and
competencies that go beyond disciplinary expertise. It is now generally accepted
that educational training as a teacher is essential to a faculty member's
effectiveness as an educator. The educational challenges across the health
professions share many similarities. In this article, we draw on the medical
education literature and focus on faculty development designed to enhance
teaching effectiveness. We first address commonly included faculty development
topics, including instructional improvement, organizational development, the
development of professional academic skills, and the teaching of specific content
areas. We then review a variety of educational approaches and formats that are
described in the literature. Included in this discussion are commonly used
workshops, seminars, short courses, and fellowships, as well as longitudinal
programs, peer coaching, mentorship, self-directed learning, and computer-aided
instruction. We also briefly explore learning at work and in communities of
practice, and we discuss several frequently encountered challenges in designing
and implementing faculty development activities, including motivating colleagues
and assessing program effectiveness. We conclude the discussion by presenting a
set of guidelines for the design of effective faculty development programs.
PMID- 17035202
TI - Historical perspective of zoo and wildlife medicine.
AB - Setting the stage for the other 12 articles on Zoological Medical Education in
this theme of articles in the Journal of Veterinary Medical Education, this
article provides a brief historical perspective on the foundation of this
discipline.
PMID- 17035203
TI - Current perspectives on curriculum needs in zoological medicine.
AB - Advances have been made in expanding veterinary curricula to deliver basic key
knowledge and skills necessary for provision of health care to captive and
companion non-domestic or non-traditional species in the veterinary colleges of
the United States and Canada. These advances were in large part facilitated by
the deliberations and recommendations of the White Oak Accords. Though a five
year review of curricular opportunities at US and Canadian veterinary colleges
shows that progress has been made in implementing the recommendations of the
White Oak Accords, there remains room for improvement. The broadly comparative
and health-maintenance basis of zoological medicine contributes critically to the
potential for veterinary medicine to make important contributions to the concept
of the integrated health of the planet. Emergence of key zoonotic and production
animal diseases derived from and within wildlife populations since 2000 has
increased awareness worldwide of the importance of zoological medicine in
protecting both production livestock and public health. These areas are addressed
in elective curricula at colleges emerging as centers of excellence in zoological
medicine, but it is critical that core curricula in zoological medicine at all
schools be strengthened to include these important areas to prepare our DVM/VMD
graduates to protect companion-animal, production-animal, and public health.
PMID- 17035204
TI - Historical perspective and future directions in training of veterinary
pathologists with an emphasis on zoo and wildlife species.
AB - This article discusses the history of the field of zoo and wildlife pathology,
training opportunities for veterinary students and graduate veterinarians, and
current and future job opportunities. The niches occupied by veterinarians in
this field and their contributions to animal and human health are also
highlighted. The field of zoo and wildlife, or "non-traditional" species,
pathology has its roots in comparative anatomy, zoology, wildlife biology, and
medical pathology in the mid- to late nineteenth century. The initial emphasis
was on comparisons between animal and human diseases or on management of game
animals. Veterinarians became increasingly involved during the twentieth century,
gradually changing the emphasis to improvement of conservation strategies,
captive care, and elucidation of diseases of concern for the animals themselves.
Currently there are several zoos and wildlife agencies in the United States
employing full-time veterinary pathologists. Private and government diagnostic
laboratories, veterinary schools, and other academic institutions in the United
States with pathology departments are other employers. The field requires post
DVM training by means of a residency program leading to board certification,
graduate school (MS or PhD degrees), or both. Veterinary students can gain
valuable experience in the field through externships and, at some schools,
through elective courses in the curriculum. Current concerns about ecosystem
health, bioterrorism, and the recognition that captive and free-ranging wildlife
can serve as sentinel species will increase the demand for veterinary
pathologists choosing this very rewarding career path specializing in non
traditional species.
PMID- 17035205
TI - Zoological medicine and public health.
AB - Public-health issues regarding zoological collections and free-ranging wildlife
have historically been linked to the risk of transmission of zoonotic diseases
and accidents relating to bites or injection of venom or toxins by venomous
animals. It is only recently that major consideration has been given worldwide to
the role of the veterinary profession in contributing to investigating zoonotic
diseases in free-ranging wildlife and integrating the concept of public health
into the management activities of game preserves and wildlife parks. At the
veterinary undergraduate level, courses in basic epidemiology, which should
include outbreak investigation and disease surveillance, but also in population
medicine, in infectious and parasitic diseases (especially new and emerging or re
emerging zoonoses), and in ecology should be part of the core curriculum. Foreign
diseases, especially dealing with zoonotic diseases that are major threats
because of possible agro-terrorism or spread of zoonoses, need to be taught in
veterinary college curricula. Furthermore, knowledge of the principles of ecology
and ecosystems should be acquired either during pre-veterinary studies or, at
least, at the beginning of the veterinary curriculum. At the post-graduate level,
master's degrees in preventive veterinary medicine, ecology and environmental
health, or public health with an emphasis on infectious diseases should be
offered to veterinarians seeking job opportunities in public health and wildlife
management.
PMID- 17035206
TI - Educating veterinarians for careers in free-ranging wildlife medicine and
ecosystem health.
AB - In the last 10 years, the field of zoological medicine has seen an expansive
broadening into the arenas of free-ranging wildlife, conservation medicine, and
ecosystem health. During the spring/summer of 2005, we prepared and disseminated
a survey designed to identify training and educational needs for individuals
entering the wildlife medicine and ecosystem health fields. Our data revealed
that few wildlife veterinarians believe that the training they received in
veterinary school adequately prepared them to acquire and succeed in their field.
Wildlife veterinarians and their employers ranked mentorship with an experienced
wildlife veterinarian, training in leadership and communication, courses and
externships in wildlife health, and additional formal training beyond the
veterinary degree as important in preparation for success. Employers, wildlife
veterinarians, and job seekers alike reported that understanding and maintaining
ecosystem health is a key component of the wildlife veterinarian's job
description, as it is critical to protecting animal health, including human
health. Today's wildlife veterinarians are a new type of transdisciplinary
professional; they practice medicine in their communities and hold titles in
every level of government and academia. It is time that we integrate ecosystem
health into our curricula to nurture and enhance an expansive way of looking at
veterinary medicine and to ensure that veterinary graduates are prepared to excel
in this new and complex world, in which the health of wildlife, domestic animals,
and people are interdependent.
PMID- 17035207
TI - Future directions in training veterinarians for companion avian species.
AB - Companion avian medicine has become a routine part of veterinary practice. More
than 16 million companion birds are owned by approximately 6.4 million US
households. This report outlines suggested undergraduate veterinary curricula,
opportunities for post-graduate education, and options for training avian
veterinarians.
PMID- 17035208
TI - A model for teaching raptor medicine in the veterinary curriculum.
AB - Injured or sick wild avian species, especially raptors (birds of prey, including
hawks, owls, falcons, and eagles), can present different challenges to veterinary
students and veterinarians who are trained in companion avian medicine (e.g.,
parrot medicine). Proper capture and restraint, feeding, housing, and certain
diagnostic and treatment techniques involving raptors require different skills,
knowledge, and resources than working with parrots. We developed an innovative
raptor medicine program that enables students to acquire proficiency in safe
capture, restraint, and examination techniques and in common diagnostic and
treatment procedures. A self-assessment survey was developed to determine
students' confidence and proficiency in 10 procedures taught in the lab. Groups
were compared by class status (Year 1 vs. Year 2 and 3) and level of prior raptor
experience (non-experienced or experienced). In surveys conducted before and
after teaching two sets of raptor training labs, students rated themselves
significantly more proficient in all 10 diagnostic and treatment procedures after
completing the two raptor laboratories. The greatest improvements were observed
in technical skill procedures such as fluid administration, intramuscular
injections, cloacal swabs, venipuncture, and bandaging. Our approach to
incorporating elective wildlife learning experiences into the veterinary
curriculum may be replicable in other veterinary schools, with or without a
wildlife rehabilitation program.
PMID- 17035209
TI - Future directions in reptile medical education.
AB - Reptile medicine has emerged as a specialty area within the broader field of
zoological medicine. It encompasses the medical needs of approximately 7,500
vertebrate species. This vertebrate class is highly diversified, having
biological and medical peculiarities that differ both between and within major
groups. Historically, veterinarians who have become recognized specialists with
reptiles have had limited formal training in their medical management. The pet
reptile trade is a multi-million-dollar business, and the popularity of reptiles
as pets has resulted in a need for more veterinarians with training in their
medical management. While few private practices have high volumes of reptile
cases, many small-animal practices will have the opportunity to see a significant
number of reptiles on an annual basis. Most practitioners with reptile medical
expertise have merged their experiences as reptile pet owners with the principles
of veterinary medicine taught in veterinary college. Several North American
veterinary colleges have reptile medicine courses, and most have didactic and
clinical courses in exotic and zoo animal medicine that include lectures and
practical experience. Most accredited zoological medicine residency training
programs include training in reptile medicine. The case load and interest in
reptile medicine will probably never be sufficient to lead the average veterinary
college to develop much more than what is currently offered. Consequently, those
few colleges having more extensive course offerings, both didactic and clinical,
will serve as educational centers for this discipline. Future Web-based teaching
programs in reptile medicine will allow students nationally and internationally
to have access to instructional material that can be continually updated.
PMID- 17035210
TI - Future directions in training of veterinarians for small exotic mammal medicine:
expectations, potential, opportunities, and mandates.
AB - Small exotic mammals have been companions to people for almost as long as dogs
and cats have been. The challenge for veterinary medicine today is to decipher
the tea leaves and determine whether small mammals are fad or transient pets or
whether they will still be popular in 20 years. This article focuses on pet small
mammal medicine, as the concerns of the laboratory animal are better known and
may differ profoundly from those of a pet. Dozens of species of small exotic
mammals are kept as pets. These pet small-mammal species have historically served
human purposes other than companionship: for hunting, for their pelts, or for
meat. Now, they are common pets. At present, most veterinary schools lack courses
in the medical care of these animals. Veterinary students need at least one
required class to introduce them to these pets. Currently, there are no small
mammal-only residency programs. This does not correspond with current needs. The
only way to judge current needs is by assessing what employers are looking for.
In a recent JAVMA classified section, almost 30% of small-animal practices in
suburban/urban areas were hiring veterinarians with knowledge of exotic pets. All
veterinarians must recognize that pet exotic small mammals have changed the
landscape of small-animal medicine. It is a reality that, today, many small
animal practices see pet exotic small mammals on a daily basis.
PMID- 17035211
TI - Future directions in training zoological medicine veterinarians.
AB - The American College of Zoological Medicine (ACZM) is dedicated to excellence in
furthering the health and well-being of both captive and free-ranging wild
animals. Currently there are 14 ACZM-approved residency programs in zoological
medicine. In addition, eight non-approved residencies and 15 internships in North
America provide training opportunities in this field. This article outlines some
of the training opportunities for both veterinary students and graduate
veterinarians that would best position them for entry into a zoological medicine
training program. Although there is a growing number of opportunities for
individuals to serve in captive and free-ranging wildlife health positions,
existing training programs are inadequate to meet these needs. It is also
acknowledged that there is an increasing number of veterinary students entering
veterinary schools with an interest in zoological medicine and that the job
market is still limited. However, positions and opportunities in zoological
medicine are available for those individuals with the drive, dedication, and
passion to succeed.
PMID- 17035212
TI - The future of training for aquatic animal health veterinarians.
AB - This article describes educational approaches for training veterinary students,
veterinary graduates, and practicing veterinarians in the area of aquatic animal
health and lists a range of general research, training, internship/residency, and
continuing-education resources.
PMID- 17035213
TI - Zoological medicine education in Canada: options and opportunities.
AB - Canada has four veterinary schools, from which approximately 325 veterinarians
graduate each year. Curricular offerings in zoological medicine consist of
limited core material and a variety of internal and external electives pursued by
students with particular interests. Several electives are offered jointly by and
rotate among the existing schools. All schools offer graduate programs that
encompass some aspects of zoological medicine. A fifth veterinary school,
expected to open in 2007, will have a stronger focus on ecosystem health and
zoological medicine. In Canada, the most effective method of increasing
educational opportunities in zoological medicine is likely through enhanced
collaboration among the five schools. Employment opportunities exist in private
veterinary practice and at universities, research establishments, provincial or
federal governments, and zoological gardens and safari parks. Increasing
recognition of the importance of ecosystem health and of the relevance of
wildlife diseases to public and domestic animal health will likely result in
additional opportunities for veterinarians with an interest in and knowledge of
zoological medicine.
PMID- 17035214
TI - Zoo and wildlife medical education: a European perspective.
AB - Europe has a long and distinguished history in veterinary science and education,
and it was here that the first professional investigations of pathological
conditions in zoo animals took place. However, despite an increasing number of
veterinarians working with wildlife, education in zoological and wildlife
medicine has only recently become part of formal veterinary training at the
undergraduate level. Consequently, current educational opportunities in
zoological and wildlife medicine vary widely throughout Europe, both in
availability and in composition. The need to establish agreed standards in
education across Europe and to foster the mobility of students and teaching staff
are reflected by international agreements such as the Bologna Treaty and the
ERASMUS-SOCRATES program. Europe is also home to a number of voluntary
professional organizations, such as the European Wildlife Disease Association and
the European Association of Zoo and Wildlife Veterinarians, that actively promote
the inclusion of zoological and wildlife medicine in veterinary education. Zoo
and wildlife medicine is currently a veterinary specialization in Europe, but
educational opportunities are likely to increase in availability in the future.
PMID- 17035215
TI - Global public health issues.
AB - The context of the conference presentation that gave rise to this article was the
importance of veterinarians becoming more engaged in the public-health challenges
of today. During the presentation, I sought to point out some of the pressing
reasons why. Of particular concern to me are the missed opportunities to help
influence human health and well-being as private veterinary practitioners in
addition to public-practice veterinarians. Key elements: Public health, the
protection and improvement of community health by organized community effort; the
global community, the entire world; social responsibility, being, as members of
society, morally and legally responsible for the welfare of human beings;
terrorism, the systematic use of terror (fear), especially as a means of coercion
(it is always local!); system integration, the interaction of interdependent
groups to form a unified whole.
PMID- 17035216
TI - The global veterinarian: the why? The what? The how?
AB - Globalization has created an entirely new landscape for veterinarians.
Opportunities abound to meet the formidable challenges presented as animals,
people, and microbes travel at a previously unimagined speed, fueled by the
engine of commerce, resulting in a plethora of new diseases, issues, and
partnerships. Re-tooling our profession to ensure that we can continue to fulfill
our veterinary oath in the face of these changes will require both short- and
long-term changes. It is essential that a single overarching, non-affiliated
organization be formed to tie together all entities, providing the structure to
create needed synergy to enhance our currently fragmented professional responses
and to solicit funds to effect necessary changes.
PMID- 17035217
TI - Global veterinary opportunities and responsibilities: some recent graduates'
perspectives.
AB - The veterinary profession has critical global responsibilities. To help meet
these responsibilities, it is critical that the training programs for veterinary
graduates provide them with the skills, knowledge, understanding, and
professional attributes pertinent to meeting these responsibilities. The programs
at US veterinary schools, in the full range from admissions, to curriculum, to
post-graduate opportunities, fall short in many critical arenas.
PMID- 17035218
TI - Veterinary medicine educational requirements to meet the needs of the US Agency
for International Development.
AB - The US Agency for International Development (USAID) works within the overall
purpose of US foreign assistance to improve the lives of the citizens of the
developing world. Through partnerships with other agencies, organizations, and
governments, and using its field offices around the world, USAID strives to
develop local capacity and thus build sustainable development. Two specific USAID
programs pertinent to veterinary medicine are global health and agriculture. In
the area of global health, veterinarians can aid USAID's work to improve the
quality, availability, and use of essential health services that specifically
target maternal and child health, HIV/AIDS, family planning and reproductive
health, infectious diseases, environmental health, nutrition, and other life
saving areas. The challenge of making the agricultural sector in a developing
country more productive is a critical one for USAID and a clear area for input
from the veterinary profession. Animal agriculture is the largest single sector
of agricultural economies in most developing countries, and livestock remains a
critical component of poverty alleviation. There are educational requirements
that benefit anyone working at USAID and can be met prior to admittance to a DVM
program, as part of a DVM curriculum, or in post-graduate training/employment,
such as proficiency in a foreign language; environmental sciences background;
familiarity with accounting and management techniques; expertise in foreign
animal diseases, zoonotic diseases, epidemiology, food safety, and nutrition, as
well as the application to human health of those areas; an advanced degree such
as an MPH; and management experience. Appropriately trained veterinarians can
make enormous contributions to USAID's global efforts to improve the health and
agriculture sectors of developing nations.
PMID- 17035219
TI - The US Army Veterinary Corps: a model for professional career development with a
public health and global perspective.
AB - The US Army Veterinary Corps is composed of approximately 420 active-duty and 200
reserve-component veterinary officers, with 40 to 45 new veterinarians joining
the active ranks each year. This article briefly summarizes the training that
members of the veterinary corps receive in preparation for their diverse range of
duties in service to the United States.
PMID- 17035220
TI - Increased student self-confidence in clinical reasoning skills associated with
case-based learning (CBL).
AB - Second-year veterinary students were surveyed at the beginning and end of a 15
week semester regarding their confidence in performing three clinical reasoning
skills: (1) making Problem Lists; (2) making Rule-Out Lists; and (3) selecting
appropriate diagnostic tests. Each week during the semester, these skills were
practiced in small-group case discussions. Changes in self-confidence were
analyzed and studied in light of faculty assessments of student competence in
performance of the three skills. RATIONALE: The purpose of the study was to
determine if students' self-confidence in performing three clinical reasoning
skills increased with practice. METHODOLOGY: On the first and last days of class,
students rated their confidence in each of the three skills on a scale of 0 to
10. Mean confidence scores for the whole class both for time points and for each
of the three skills were analyzed. RESULTS: There were significant increases in
students' self-confidence in all three clinical reasoning skills over the
semester each year. A greater percentage of students expressed improved
confidence in selecting appropriate diagnostic tests than in the other two skills
in three of the four years studied. CONCLUSIONS: Students' self-confidence in
performing three clinical reasoning skills improved over the course of a semester
in which they practiced the skills in a CBL format. Subjective faculty assessment
of students' competence in these skills generally indicated improvement. However,
no meaningful conclusions about the correlation of skill competence and student
confidence could be drawn because of inadequacies in the measurement of student
performance.
PMID- 17035221
TI - Predictors of depression and anxiety in first-year veterinary students: a
preliminary report.
AB - Historically, veterinary medical students' mental health has rarely been
investigated, but recently there has been renewed interest in this topic. The
present study evaluated depression and anxiety levels in a cross-sectional
investigation of 93 first-year veterinary medical students enrolled at Kansas
State University (KSU). During their first semester, students completed the
Center for Epidemiological Studies Depression Scale (CES-D) and the Mental Health
Inventory's Anxiety Scale (MHI-A). Results indicate that 32% of these first-year
KSU veterinary students were experiencing clinical levels of depressive symptoms.
Additionally, students reported elevated anxiety scores. Predictors of depression
and anxiety levels include homesickness, physical health, and unclear instructor
expectations. Areas of intervention with a focus on improving veterinary medical
student well-being are discussed.
PMID- 17035222
TI - Forecasting veterinary school admission probabilities for undergraduate student
profiles.
AB - Increased competition for veterinary school admission has created a need to
determine whether individual students are likely to be successful candidates for
veterinary school admission early in their undergraduate careers. Students invest
considerable time and money in pre-veterinary courses of study, hoping for
acceptance into professional veterinary school. A forecasting model was developed
to predict the likelihood of students with particular characteristics gaining
acceptance. Characteristics such as gender, age, size of high school, and ACT,
are known upon entrance into college and can be used to determine the likelihood
of an individual's being accepted. Data were gathered from the Louisiana State
University College of Veterinary Medicine (LSU-CVM) admissions for all students
applying to veterinary school for the classes of 2006 through 2008 from the top
two agricultural programs in the state in terms of quantity of applicants to
veterinary school: Louisiana State University and Louisiana Tech University. A
one-way ANOVA was used to examine whether there were any statistical differences
between known demographic and performance variables and acceptance into
veterinary school. A logit forecasting model was then estimated to predict the
likelihood of gaining acceptance into veterinary school based only on variables
known early in the student's undergraduate career. Age, gender, and ACT scores
were determined to be important variables in determining the likelihood of
gaining admission. Overall, the forecasting model is of use in assigning
probabilities of acceptance into veterinary school for specific student profiles,
which can assist in one-on-one assistance from advisor to student.
PMID- 17035223
TI - Evaluation of traditional instruction versus a self-learning computer module in
teaching veterinary students how to pass a nasogastric tube in the horse.
AB - OBJECTIVE: To evaluate the effectiveness of a self-learning computer module
(SLCM) versus traditional instruction in teaching how to pass a nasogastric tube
(NG) in the horse. DESIGN: A double-blind, monocentric study. SAMPLE POPULATION:
52 third-year students in the DVM program were randomly assigned to two groups:
traditional instruction (N = 25) or SLCM instruction (N = 27). PROCEDURE:
Traditional instruction consisted of an instructor and live demonstration; SCLM
students were given a CD-ROM each. Both sessions lasted one hour. The students
were then united in one session to practice passing the NG tube. Their
performance was videotaped and evaluated by two evaluators. Students were then
given a multiple-choice knowledge quiz. One week later, a second demonstration of
the same procedure by the two methods was administered, and students were allowed
to choose either method of instruction. A Likert-scale questionnaire about their
comfort, their confidence, and the appropriateness of the teaching method was
given after the second demonstration. Data were analyzed by non-parametric tests.
A focus-group study was conducted to determine students' perception of each
teaching method. Nine participants in the experiment volunteered for these focus
group sessions. The sessions were audiotaped and transcribed. RESULTS: Students
in the SLCM group performed significantly better on the test of knowledge than
traditionally instructed students. The questionnaire found significant perceived
benefits to computer-based instruction, including a preference for the computer
based module, better learning, and greater preparedness. In hands-on skill, time
to pass the NG tube on the successful attempt was significantly shorter in the
SLCM group than in the traditionally instructed group. The data from focus-group
sessions suggest that while participants expressed satisfaction with both modes
of instruction, the SLCM group reported somewhat higher levels of confidence in
their skills prior to performing the procedure. Whereas the traditional group
reported a strong preference for continued live demonstrations of the procedure,
the SLCM group stated that the computer-assisted module alone provided them with
effective instruction. CONCLUSION: Computer-assisted learning is an acceptable
and effective method of training students to pass an NG tube with potential
welfare, proficiency, and knowledge advantages.
PMID- 17035224
TI - A comparison of linear, fixed-form computer-based testing versus traditional
paper-and-pencil-format testing in veterinary medical education.
AB - Computerized testing has made significant inroads into veterinary education.
Traditional paper-and-pencil examination formats are being replaced by computer
based testing (CBT). Computer-administered, fixed-form tests, because they mimic
most closely the familiar fixed-response paper-and-pencil test formats, might
intuitively seem to be inherently equivalent to their paper-and-pencil
counterparts. However, research examining test-mode effects on student
performance presents a very mixed picture. Additionally, students often report
that they feel their performance is adversely affected by CBT and that their
grades on the computer-based exams are lower than they would have been on the
more familiar paper-and-pencil format. In order to address student perceptions of
negative impact and the mixed nature of the published research results on the
topic, a study was conducted to assess whether the transition from paper-and
pencil to equivalent linear CBT exams did, in fact, affect students' examination
scores. This study found no evidence for significant test-mode effects on student
scores as a result of the introduction of computer-based testing into the
veterinary curriculum.
PMID- 17035225
TI - An electronic instructor for gross anatomy dissection.
AB - Gross anatomy is time consuming to teach and to learn. Because the process of
dissection takes up so much student time, assistance in the form of an in-lab
instructional DVD program might improve student performance. The DVD could be
viewed with a portable device by individual dissection groups at their tables.
Groups could dissect at their own pace, with access to step-by-step
demonstrations and answers to frequently asked anatomical questions. We created
an instructional DVD program demonstrating dissection of the canine ventral neck
and thoracic limb. The effect on student exam scores of using the DVD versus not
using it was measured in a controlled, two-sample study using incoming first-year
veterinary students as volunteers. Volunteers were told the study was of two
different dissection methods; the DVD was not specifically mentioned until after
the students were separated into two groups (Blue/DVD group and Orange/No DVD
group), and then only to volunteers in the Blue group. Except for the DVD, the
two groups had the same resources. The difference in scores on an exam given
after a single dissection period did not differ sufficiently to conclude that DVD
use raised the mean score; however, 73% of the DVD group scored 60% or higher,
while only 38% of the No DVD group scored 60% or higher. The difference in mean
scores overall was 2.3 points out of a possible 49, suggesting that the DVD
helped students, especially those with lower scores, to earn two to three more
points than they would have otherwise.
PMID- 17035226
TI - Learning evidence-based veterinary medicine through development of a critically
appraised topic.
AB - Evidence-based veterinary medicine is a relatively new field of study. Increased
knowledge of medicine coupled with the increased ability of computers and other
electronic devices present overwhelming information. The critically appraised
topic (CAT) is one method to gather and evaluate information related to a
clinical question. CATs in informatics are short summaries of evidence, usually
found through literature searches, in response to a specifically stated,
clinically oriented problem or question. This article describes a study in which
each first-year veterinary student developed a CAT as a class project. The
results of this project indicate that students were able to successfully develop
CATs and that this exercise helped them understand evidence-based veterinary
medicine concepts. Though some modification in this project will be made in the
future, overall it was a worthwhile effort and will remain as an activity in the
course.
PMID- 17035227
TI - Membrane topology and identification of key functional amino acid residues of
murine acyl-CoA:diacylglycerol acyltransferase-2.
AB - Triacylglycerols are the predominant molecules of energy storage in eukaryotes.
However, excessive accumulation of triacylglycerols in adipose tissue leads to
obesity and, in nonadipose tissues, is associated with tissue dysfunction. Hence,
it is of great importance to have a better understanding of the molecular
mechanisms of triacylglycerol synthesis. The final step in triacylglycerol
synthesis is catalyzed by the acyl-CoA:diacylglycerol acyltransferase (DGAT)
enzymes, DGAT1 and DGAT2. Although recent studies have shed light on metabolic
functions of these enzymes, little is known about the molecular aspects of their
structures or functions. Here we report the topology for murine DGAT2 and the
identification of key amino acids that likely contribute to enzymatic function.
Our data indicate that DGAT2 is an integral membrane protein with both the N and
C termini oriented toward the cytosol. A long hydrophobic region spanning amino
acids 66-115 likely comprises two transmembrane domains or, alternatively, a
single domain that is embedded in the membrane bilayer. The bulk of the protein
lies distal to the transmembrane domains. This region shares the highest degree
of homology with other enzymes of the DGAT2 family and contains a sequence HPHG
that is conserved in all family members. Mutagenesis of this sequence in DGAT2
demonstrated that it is required for full enzymatic function. Additionally, a
neutral lipid-binding domain that is located in the putative first transmembrane
domain was also required for full enzymatic function. Our findings provide the
first insights into the topography and molecular aspects of DGAT2 and related
enzymes.
PMID- 17035228
TI - The human sef-a isoform utilizes different mechanisms to regulate receptor
tyrosine kinase signaling pathways and subsequent cell fate.
AB - Negative feedback is among the key mechanisms for regulating receptor tyrosine
kinase (RTK) signaling. Human Sef, a recently identified inhibitor of RTK
signaling, encodes different isoforms, including a membrane spanning (hSef-a) and
a cytosolic (hSef-b) isoform. Previously, we reported that hSef-b inhibited
fibroblast proliferation and prevented the activation of mitogen-activated
protein kinase (MAPK), without affecting protein kinase B/Akt or p38 MAPK.
Conflicting results were reported concerning hSef-a inhibition of MAPK
activation, and the effect of hSef-a on other RTK-induced signaling pathways is
unknown. Here we show that, in fibroblasts, similar to hSef-b, ectopic expression
of hSef-a inhibited fibroblast growth factor-induced cell proliferation. Unlike
hSef-b, however, the growth arrest was mediated via a MAPK-independent mechanism,
and was accompanied by elevated p38 MAPK phosphorylation and inhibition of
protein kinase B/Akt. In addition, hSef-a, but not hSef-b, mediated apoptosis in
fibroblast growth factor-stimulated cells. Chemical inhibitor of p38 MAPK
abrogated the effect of hSef-a on apoptosis. In epithelial cells, ectopic
expression of hSef-a inhibited the activation of MAPK, whereas down-regulation of
endogenous hSef-a significantly increased MAPK activation and accelerated growth
factor-dependent cell proliferation. These results indicate that hSef-a is a
multifunctional negative modulator of RTK signaling and clearly demonstrate that
hSef-a can inhibit the activation of MAPK, although in a cell type-specific
manner. Moreover, the differences between the activities of hSef-a and hSef-b
suggest that hSef isoforms can control signal specificity and subsequent cell
fate by utilizing different mechanisms to modulate RTK signaling.
PMID- 17035229
TI - Small C-terminal domain phosphatases dephosphorylate the regulatory linker
regions of Smad2 and Smad3 to enhance transforming growth factor-beta signaling.
AB - Transforming growth factor-beta (TGF-beta) controls a diverse set of cellular
processes, and its canonical signaling is mediated via TGF-beta-induced
phosphorylation of receptor-activated Smads (2 and 3) at the C-terminal SXS
motif. We recently discovered that PPM1A can dephosphorylate Smad2/3 at the C
terminal SXS motif, implicating a critical role for phosphatases in regulating
TGF-beta signaling. Smad2/3 activity is also regulated by phosphorylation in the
linker region (and N terminus) by a variety of intracellular kinases, making it a
critical platform for cross-talk between TGF-beta and other signaling pathways.
Using a functional genomic approach, we identified the small C-terminal domain
phosphatase 1 (SCP1) as a specific phosphatase for Smad2/3 dephosphorylation in
the linker and N terminus. A catalytically inactive SCP1 mutant (dnSCP1) had no
effect on Smad2/3 phosphorylation in vitro or in vivo. Of the other FCP/SCP
family members SCP2 and SCP3, but not FCP1, could also dephosphorylate Smad2/3 in
the linker/N terminus. Depletion of SCP1/2/3 enhanced Smad2/3 linker
phosphorylation. SCP1 increased TGF-beta-induced transcriptional activity in
agreement with the idea that phosphorylation in the Smad2/3 linker must be
removed for a full transcriptional response. SCP1 overexpression also counteracts
the inhibitory effect of epidermal growth factor on TGF-beta-induced p15
expression. Taken together, this work identifies the first example of a Smad2/3
linker phosphatase(s) and reveals an important new substrate for SCPs.
PMID- 17035230
TI - Autocrine and juxtacrine effects of amphiregulin on the proliferative, invasive,
and migratory properties of normal and neoplastic human mammary epithelial cells.
AB - Amphiregulin (AR) autocrine loops have been associated with several types of
cancer. We demonstrate that SUM149 breast cancer cells have a self-sustaining AR
autocrine loop. SUM149 cells are epidermal growth factor (EGF)-independent for
growth, and they overexpress AR mRNA, AR membrane precursor protein, and secreted
AR relative to the EGF-dependent human mammary epithelial cell line MCF10A.
MCF10A cells made to overexpress AR (MCF10A AR) are also EGF-independent for
growth. Treatment with the pan-ErbB inhibitor CI1033 and the anti-EGF receptor
(EGFR) antibody C225 demonstrated that ligand-mediated activation of EGFR is
required for SUM149 cell proliferation. AR-neutralizing antibody significantly
reduced both SUM149 EGFR activity and cell proliferation, confirming that an AR
autocrine loop is required for mitogenesis in SUM149 cells. EGFR tyrosine
phosphorylation was dramatically decreased in both SUM149 and MCF10A AR cells
after inhibition of AR cleavage with the broad spectrum metalloprotease inhibitor
GM6001, indicating that an AR autocrine loop is strictly dependent on AR cleavage
in culture. However, a juxtacrine assay where fixed SUM149 cells and MCF10A AR
cells were overlaid on top of EGF-deprived MCF10A cells showed that the AR
membrane precursor can activate EGFR. SUM149 cells, MCF10A AR cells, and MCF10A
cells growing in exogenous AR were all considerably more invasive and motile than
MCF10A cells grown in EGF. Moreover, AR up-regulates a number of genes involved
in cell motility and invasion in MCF10A cells, suggesting that an AR autocrine
loop contributes to the aggressive breast cancer phenotype.
PMID- 17035231
TI - RPA2 is a direct downstream target for ATR to regulate the S-phase checkpoint.
AB - Upon DNA damage, replication is inhibited by the S-phase checkpoint. ATR (ataxia
telangiectasia mutated- and Rad3-related) is specifically involved in the
inhibition of replicon initiation when cells are treated with DNA damage-inducing
agents that stall replication forks, but the mechanism by which it acts to
prevent replication is not yet fully understood. We observed that RPA2 is
phosphorylated on chromatin in an ATR-dependent manner when replication forks are
stalled. Mutation of the ATR-dependent phosphorylation sites in RPA2 leads to a
defect in the down-regulation of DNA synthesis following treatment with UV
radiation, although ATR activation is not affected. Threonine 21 and serine 33,
two residues among several phosphorylation sites in the amino terminus of RPA2,
are specifically required for the UV-induced, ATR-mediated inhibition of DNA
replication. RPA2 mutant alleles containing phospho-mimetic mutations at ATR
dependent phosphorylation sites have an impaired ability to associate with
replication centers, indicating that ATR phosphorylation of RPA2 directly affects
the replication function of RPA. Our studies suggest that in response to UV
induced DNA damage, ATR rapidly phosphorylates RPA2, disrupting its association
with replication centers in the S-phase and contributing to the inhibition of DNA
replication.
PMID- 17035232
TI - Gastrointestinal hormones cause rapid c-Met receptor down-regulation by a novel
mechanism involving clathrin-mediated endocytosis and a lysosome-dependent
mechanism.
AB - The activated c-Met receptor has potent effects on normal tissues and tumors. c
Met levels are regulated by hepatocyte growth factor (HGF); however, it is
unknown if they can be regulated by gastrointestinal (GI) hormones. c-Met is
found in many GI tissues/tumors that possess GI hormone receptors. We studied the
effect of GI hormones on c-Met in rat pancreatic acini, which possess both
receptors. CCK-8, carbachol, and bombesin, but not VIP/secretin, decreased c-Met.
CCK-8 caused rapid and potent c-Met down-regulation and abolished HGF-induced c
Met and Gab1 tyrosine phosphorylation, while stimulating c-Met serine
phosphorylation. The effect of cholecystokinin (CCK) was also seen in intact
acini using immunofluorescence, in a biotinylated fraction representing membrane
proteins, in single acinar cells, in Panc-1 tumor cells, and in vivo in rats
injected with CCK. CCK-8 did not decrease cell viability or overall
responsiveness. GF109203X, thapsigargin, or their combination partially reversed
the effect of CCK-8. In contrast to HGF-induced c-Met down-regulation, the effect
of CCK was decreased by a lysosome inhibitor (concanamycin) but not the
proteasome inhibitor lactacystin. Inhibitors of clathrin-mediated endocytosis
blocked the effect of CCK. HGF but not CCK-8 caused c-Met ubiquitination. These
results show CCK and other GI hormones can cause rapid c-Met down-regulation,
which occurs by a novel mechanism. These results could be important for c-Met
regulation in normal as well as in neoplastic tissue in the GI tract.
PMID- 17035233
TI - Suppressing Wnt signaling by the hedgehog pathway through sFRP-1.
AB - The hedgehog (Hh) signaling pathway is essential for embryonic development and
carcinogenesis. Activation of Hh signaling has been identified in several types
of gastrointestinal cancers, including esophageal, gastric, pancreatic, and liver
cancers. Several recent studies suggest that Hh signaling activation can inhibit
Wnt signaling. However, the molecular basis underlying this inhibition remains
unclear. As transcription factors in the Hh signaling pathway, Gli molecules
transform cells in culture, and their expression are associated with cancer
development. Here we report that expression of a secreted frizzled-related
protein-sFRP-1 in mouse embryonic fibroblasts is dependent on Gli1 and Gli2. In
human gastric cancer cells, inhibition of Hh signaling reduces the level of sFRP
1 transcript, whereas ectopic expression of Gli1 increases the level of sFRP-1
transcript. Results from chromatin immunoprecipitation indicate that Gli1 is
involved in transcriptional regulation of sFRP-1. In 293 cells with Gli1
expression, Wnt-1-mediated beta-catenin accumulation in the cytosol and DKK1
expression are all abrogated, which can be reversed by inhibiting sFRP-1
expression. Furthermore, while SIIA cells do not respond to Wnt-1-conditioned
medium, inhibition of Hh signaling by smoothened (SMO) antagonist KAAD
cyclopamine (keto-N-aminoethylaminocaproyldihydrocinnamoylcyclopamine) leads to
Wnt1-mediated beta-catenin accumulation in the cytosol. These data indicate that
sFRP-1, a target gene of the hedgehog pathway, is involved in cross-talk between
the hedgehog pathway and the Wnt pathway.
PMID- 17035234
TI - Physical and functional interaction of the p14ARF tumor suppressor with
ribosomes.
AB - Alterations in the p14(ARF) tumor suppressor are frequent in many human cancers
and are associated with susceptibility to melanoma, pancreatic cancer, and
nervous system tumors. In addition to its p53-regulatory functions, p14(ARF) has
been shown to influence ribosome biogenesis and to regulate the endoribonuclease
B23, but there remains considerable controversy about its nucleolar role. We
sought to clarify the activities of p14(ARF) by studying its interaction with
ribosomes. We show that p14(ARF) and B23 interact within the nucleolar 60 S
preribosomal particle and that this interaction does not require rRNA. In
contrast to previous reports, we found that expression of p14(ARF) does not
significantly alter ribosome biogenesis but inhibits polysome formation and
protein translation in vivo. These results suggest a ribosome-dependent p14(ARF)
pathway that regulates cell growth and thus complements p53-dependent p14(ARF)
functions.
PMID- 17035235
TI - Determinants of RING-E2 fidelity for Hrd1p, a membrane-anchored ubiquitin ligase.
AB - A critical aspect of E3 ubiquitin ligase function is the selection of a
particular E2 ubiquitin-conjugating enzyme to accomplish ubiquitination of a
substrate. We examined the requirements for correct E2-E3 specificity in the RING
H2 ubiquitin ligase Hrd1p, an ER-localized protein known to use primarily Ubc7p
for its function. Versions of Hrd1p containing the RING motif from homologous E3s
were unable to carry out Hrd1p function, revealing a requirement for the specific
Hrd1p RING motif in vivo. An in vitro assay revealed that these RING motifs were
sufficient to function as ubiquitin ligases, but that they did not display the E2
specificity predicted from in vivo results. We further refined the in vitro assay
of Hrd1p function by demanding not only ubiquitin ligase activity, but also
specific activity that recapitulated both the E2 specificity and RING selectivity
observed in vivo. Doing so revealed that correct E2 engagement by Hrd1p required
the presence of portions of the Hrd1p soluble cytoplasmic domain outside the RING
motif, the placement of the Hrd1p ubiquitin ligase in the ER membrane, and
presentation of Ubc7p in the cytosolic context. We confirmed that these
conditions supported the ubiquitination of Hrd1p itself, and the transfer of
ubiquitin to the prototype substrate Hmg2p-GFP, validating Hrd1p self
ubiquitination as a viable assay of ligase function.
PMID- 17035236
TI - Post-meiotic shifts in HSPA2/HSP70.2 chaperone activity during mouse
spermatogenesis.
AB - HSPA2 (formerly HSP70.2) is a testis-specific member of the HSP70 family known to
play a critical role in the completion of meiosis during male germ cell
differentiation. Although abundantly present in post-meiotic cells, its function
during spermiogenesis remained obscure. Here, using a global proteomic approach
to identify genome-organizing proteins in condensing spermatids, we discovered an
unexpected role for HSPA2, which acquires new functions and becomes tightly
associated with major spermatid DNA-packaging proteins, transition proteins 1 and
2. Hence, HSPA2 is identified here as the first transition protein chaperone, and
these data shed a new light on the yet totally unknown process of genome
condensing structure assembly in spermatids.
PMID- 17035237
TI - CD4 and CCR5 constitutively interact at the plasma membrane of living cells: a
confocal fluorescence resonance energy transfer-based approach.
AB - Human immunodeficiency virus entry into target cells requires sequential
interactions of the viral glycoprotein envelope gp120 with CD4 and chemokine
receptors CCR5 or CXCR4. CD4 interaction with the chemokine receptor is suggested
to play a critical role in this process but to what extent such a mechanism takes
place at the surface of target cells remains elusive. To address this issue, we
used a confocal microspectrofluorimetric approach to monitor fluorescence
resonance energy transfer at the cell plasma membrane between enhanced blue and
green fluorescent proteins fused to CD4 and CCR5 receptors. We developed an
efficient fluorescence resonance energy transfer analysis from experiments
carried out on individual cells, revealing that receptors constitutively interact
at the plasma membrane. Binding of R5-tropic HIV gp120 stabilizes these
associations thus highlighting that ternary complexes between CD4, gp120, and
CCR5 occur before the fusion process starts. Furthermore, the ability of CD4
truncated mutants and CCR5 ligands to prevent association of CD4 with CCR5
reveals that this interaction notably engages extracellular parts of receptors.
Finally, we provide evidence that this interaction takes place outside raft
domains of the plasma membrane.
PMID- 17035238
TI - Photon flux density-dependent gene expression in Synechocystis sp. PCC 6803 is
regulated by a small, redox-responsive, LuxR-type regulator.
AB - The expression of many cyanobacterial genes is regulated by the redox state of
the photosynthetic electron transport chain. However, factors involved in this
regulation have not been identified. In this study, we demonstrate that a small
LuxR-type regulator in Synechocystis sp. PCC 6803, PedR (Ssl0564), senses the
activity of photosynthetic electron transport to achieve the photon flux density
dependent transcriptional regulation. PedR is constitutively expressed in
Synechocystis cells and exists as a dimer bridged by intermolecular disulfide
bond(s). It activates the expression of chlL, chlN, chlB, and slr1957 and
represses that of ndhD2, rpe, and the pedR (ssl0564)-sll0296 operon under
conditions where the activity of photosynthetic electron transport is low. When
the supply of reducing equivalents from photosynthetic electron transport chain
increases upon the elevation of photon flux density, PedR is inactivated through
its conformational change within 5 min. This mechanism enables transient
induction or repression of the target genes in response to sudden changes in
light environment. The fact that orthologs of PedR are conserved among all the
cyanobacterial genomes sequenced so far indicates that this type of
transcriptional regulation is essential for cyanobacteria to acclimate to
changing environments.
PMID- 17035239
TI - Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic
domain conformation of the ubiquitin-specific protease 8 (USP8).
AB - Ubiquitin-specific protease 8 (USP8) hydrolyzes mono and polyubiquitylated
targets such as epidermal growth factor receptors and is involved in clathrin
mediated internalization. In 1182 residues, USP8 contains multiple domains,
including coiled-coil, rhodanese, and catalytic domains. We report the first high
resolution crystal structures of these domains and discuss their implications for
USP8 function. The amino-terminal domain is a homodimer with a novel fold. It is
composed of two five-helix bundles, where the first helices are swapped, and
carboxyl-terminal helices are extended in an antiparallel fashion. The structure
of the rhodanese domain, determined in complex with the E3 ligase NRDP1, reveals
the canonical rhodanese fold but with a distorted primordial active site. The
USP8 recognition domain of NRDP1 has a novel protein fold that interacts with a
conserved peptide loop of the rhodanese domain. A consensus sequence of this loop
is found in other NRDP1 targets, suggesting a common mode of interaction. The
structure of the carboxyl-terminal catalytic domain of USP8 exhibits the
conserved tripartite architecture but shows unique traits. Notably, the active
site, including the ubiquitin binding pocket, is in a closed conformation,
incompatible with substrate binding. The presence of a zinc ribbon subdomain near
the ubiquitin binding site further suggests a polyubiquitin-specific binding site
and a mechanism for substrate induced conformational changes.
PMID- 17035240
TI - Indirect recognition in sequence-specific DNA binding by Escherichia coli
integration host factor: the role of DNA deformation energy.
AB - Integration host factor (IHF) is a bacterial histone-like protein whose primary
biological role is to condense the bacterial nucleoid and to constrain DNA
supercoils. It does so by binding in a sequence-independent manner throughout the
genome. However, unlike other structurally related bacterial histone-like
proteins, IHF has evolved a sequence-dependent, high affinity DNA-binding motif.
The high affinity binding sites are important for the regulation of a wide range
of cellular processes. A remarkable feature of IHF is that it employs an indirect
readout mechanism to bind and wrap DNA at both the nonspecific and high affinity
(sequence-dependent) DNA sites. In this study we assessed the contributions of
pre-formed and protein-induced DNA conformations to the energetics of IHF
binding. Binding energies determined experimentally were compared with energies
predicted for the IHF-induced deformation of the DNA helix (DNA deformation
energy) in the IHF-DNA complex. Combinatorial sets of de novo DNA sequences were
designed to systematically evaluate the influence of sequence-dependent
structural characteristics of the conserved IHF recognition elements of the
consensus DNA sequence. We show that IHF recognizes pre-formed conformational
characteristics of the consensus DNA sequence at high affinity sites, whereas at
all other sites relative affinity is determined by the deformational energy
required for nearest-neighbor base pairs to adopt the DNA structure of the bound
DNA-IHF complex.
PMID- 17035241
TI - Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity
to store depletion-induced apoptosis in neural cells.
AB - An increase in the cytoplasmic-free Ca(2+) concentration mediates cellular
responses to environmental signals that influence a range of processes, including
gene expression, motility, secretion of hormones and neurotransmitters, changes
in energy metabolism, and apoptosis. Mitochondria play important roles in
cellular Ca(2+) homeostasis and signaling, but the roles of specific
mitochondrial proteins in these processes are unknown. Uncoupling proteins (UCPs)
are a family of proteins located in the inner mitochondrial membrane that can
dissociate oxidative phosphorylation from respiration, thereby promoting heat
production and decreasing oxyradical production. Here we show that UCP4, a
neuronal UCP, influences store-operated Ca(2+) entry, a process in which
depletion of endoplasmic reticulum Ca(2+) stores triggers Ca(2+) influx through
plasma membrane "store-operated" channels. PC12 neural cells expressing human
UCP4 exhibit reduced Ca(2+) entry in response to thapsigargin-induced endoplasmic
reticulum Ca(2+) store depletion. The elevations of cytoplasmic and
intramitochondrial Ca(2+) concentrations and mitochondrial oxidative stress
induced by thapsigargin were attenuated in cells expressing UCP4. The
stabilization of Ca(2+) homeostasis and preservation of mitochondrial function by
UCP4 was correlated with reduced mitochondrial reactive oxygen species
generation, oxidative stress, and Gadd153 up-regulation and increased resistance
of the cells to death. Reduced Ca(2+)-dependent cytosolic phospholipase A2
activation and oxidative metabolism of arachidonic acid also contributed to the
stabilization of mitochondrial function in cells expressing human UCP4. These
findings demonstrate that UCP4 can regulate cellular Ca(2+) homeostasis,
suggesting that UCPs may play roles in modulating Ca(2+) signaling in
physiological and pathological conditions.
PMID- 17035242
TI - Human Daxx-mediated repression of human cytomegalovirus gene expression
correlates with a repressive chromatin structure around the major immediate early
promoter.
AB - Upon herpesvirus infection, viral DNA becomes associated with nuclear structures
known as nuclear domain 10 (ND10). The role of ND10 during herpesvirus infection
has long been contentious; data arguing for a role for ND10 in repression of
infection have been countered by other data showing little effect of ND10 on
virus infection. Here we show that knockdown of human Daxx (hDaxx) expression, an
important component of ND10, prior to infection with human cytomegalovirus
resulted in increased levels of viral immediate early RNA and protein expression
and that this correlated with an increased association of the major immediate
early promoter with markers of transcriptionally active chromatin. Conversely, we
also show that stable overexpression of hDaxx renders cells refractory to
cytomegalovirus immediate early gene expression. Intriguingly, this hDaxx
mediated repression appears to be restricted to cells stably overexpressing hDaxx
and is not recapitulated in transient transfection assays. Finally, hDaxx
mediated repression of cytomegalovirus major immediate early gene expression was
overcome by infecting at higher virus titers, suggesting that an incoming viral
structural protein or viral DNA is responsible for overcoming the repression of
viral gene expression in hDaxx superexpressing cells. These data suggest that
hDaxx in ND10 functions at the site of cytomegalovirus genome deposition to
repress transcription of incoming viral genomes and that this repression is
mediated by a direct and immediate effect of hDaxx on chromatin modification
around the viral major immediate early promoter.
PMID- 17035243
TI - Act1 adaptor protein is an immediate and essential signaling component of
interleukin-17 receptor.
AB - Interleukin (IL)-17, the founding member of the IL-17 cytokine family, is the
hallmark of a novel subset of CD4+ T cells that is regulated by TGFbeta, IL-6,
and IL-23. IL-17 plays an important role in promoting tissue inflammation in host
defense against infection and in autoimmune diseases. Although IL-17 has been
reported to regulate the expression of proinflammatory cytokines, chemokines, and
matrix metalloproteinases, the signaling mechanism of IL-17 receptor has not been
understood. An earlier study found that IL-17 activates NF-kappaB and MAPK
pathways and requires TRAF6 to induce IL-6. However, it is unknown what
molecule(s) directly associates with IL-17 receptor to initiate the signaling. We
demonstrate here that IL-17 receptor family shares sequence homology in their
intracellular region with Toll-IL-1 receptor (TIR) domains and with Act1, a novel
adaptor previously reported as an NF-kappaB activator. MyD88 and IRAK4,
downstream signaling components of TIR, are not required for IL-17 signaling. On
the other hand, Act1 and IL-17 receptor directly associate likely via homotypic
interaction. Deficiency of Act1 in fibroblast abrogates IL-17-induced cytokine
and chemokine expression, as well as the induction of C/EBPbeta, C/EBPdelta, and
IkappaBzeta. Also, absence of Act1 results in a selective defect in IL-17-induced
activation of NF-kappaB pathway. These results thus indicate Act1 as a membrane
proximal adaptor of IL-17 receptor with an essential role in induction of
inflammatory genes. Our study not only for the first time reveals an immediate
signaling mechanism downstream of an IL-17 family receptor but also has
implications in therapeutic treatment of various immune diseases.
PMID- 17035244
TI - Cross-linking between helices within subunit a of Escherichia coli ATP synthase
defines the transmembrane packing of a four-helix bundle.
AB - Subunit a of F(1)F(0) ATP synthase is required in the H(+) transport driven
rotation of the c-ring of F(0), the rotation of which is coupled to ATP synthesis
in F(1). The three-dimensional structure of subunit a is unknown. In this study,
Cys substitutions were introduced into two different transmembrane helices (TMHs)
of subunit a, and the proximity of the thiol side chains was tested via attempted
oxidative cross-linking to form the disulfide bond. Pairs of Cys substitutions
were made in TMHs 2/3, 2/4, 2/5, 3/4, 3/5, and 4/5. Cu(+2)-catalyzed oxidation
led to cross-link formation between Cys pairs L120C(TMH2) and S144C(TMH3),
L120C(TMH2) and G218C(TMH4), L120C(TMH2) and H245C(TMH5), L120C(TMH2) and
I246C(TMH5), N148C(TMH3) and E219C(TMH4), N148C(TMH3) and H245C(TMH5), and
G218C(TMH4) and I248C(TMH5). Iodine, but not Cu(+2), was found to catalyze cross
link formation between D119C(TMH2) and G218C(TMH4). The results suggest that TMHs
2, 3, 4, and 5 form a four-helix bundle with one set of key functional residues
in TMH4 (Ser-206, Arg-210, and Asn-214) located at the periphery facing subunit
c. Other key residues in TMHs 2, 4, and 5, which were concluded previously to
compose a possible aqueous access pathway from the periplasm, were found to
locate to the inside of the four-helix bundle.
PMID- 17035245
TI - Brief interventions for at-risk drinking: patient outcomes and cost-effectiveness
in managed care organizations.
AB - AIMS: Evaluate effectiveness and costs of brief interventions for patients
screening positive for at-risk drinking in managed health care organizations
(MCOs). METHODS: A pre-post, quasi-experimental, multi-site evaluation conducted
at 15 clinic sites within five MCO settings. At-risk drinkers (N = 1329) received
either: (i) brief intervention delivered by licensed practitioners; or (ii) brief
intervention delivered by mid-level professional specialists (nurses); or (iii)
usual care (comparison condition). Clinics were randomly assigned to three study
conditions. Data were collected on the cost of screening and brief intervention.
Follow-up interviews were conducted at 3 and 12 months. RESULTS: Participants in
all three study conditions were drinking significantly less at 3-month follow-up,
but the decline was significantly greater in the two intervention groups than in
the control group. There were no significant differences between the two
intervention conditions. Of the patients in the intervention conditions 60%
reduced their alcohol consumption by > or =1 drink per week, compared with 53% of
those in the control condition. No differences were found on a measure of the
quality of life. Differential reductions in weekly alcohol consumption between
intervention and control groups were significant at 12-month follow-up. Average
incremental costs of the interventions were 4.16 US dollar per patient using
licensed practitioners and 2.82 US dollar using mid-level specialists.
CONCLUSION: Alcohol screening and brief intervention when implemented in managed
care organizations produces modest, statistically significant reductions in at
risk drinking. Interventions delivered to a common protocol by mid-level
specialists are as effective as those delivered by licensed practitioners at
about two-thirds the cost.
PMID- 17035246
TI - Identification of susceptibility loci for cervical carcinoma by genome scan of
affected sib-pairs.
AB - Cervical cancer is caused by a combination of environmental and genetic risk
factors. Infection by oncogenic types of human papillomavirus is recognized as
the major environmental risk factor and epidemiological studies indicate that
host genetic factors predispose to disease development. A number of genetic
susceptibility factors have been proposed, but with exception of the human
leukocyte antigen CHLA, class II, have not shown consistent results among
studies. We have performed the first genomewide linkage scan using 278 affected
sib-pairs to identify loci involved in susceptibility to cervical cancer. A two
step qualitative non-parametric linkage analysis using 387 microsatellites with
an average spacing of 10.5 cM revealed excess allelic sharing at nine regions on
eight chromosomes. These regions were further analysed with 125 markers to
increase the map density to 1.28 cM. Nominal significant linkage was found for
three of the nine loci [9q32 (maximum lod-score, MLS) =1.95, P<0.002), 12q24
(MLS=1.25, P<0.015) and 16q24 (MLS=1.35, P<0.012)]. These three regions have
previously been connected to human cancers that share characteristics with
cervical carcinoma, such as esophageal cancer and Hodgkin's lymphoma. A number of
candidate genes involved in defence against viral infections, immune response and
tumour suppression are found in these regions. One such gene is the thymic
stromal co-transporter (TSCOT). Analyses of TSCOT single nucleotide polymorphisms
further strengthen the linkage to this region (MLS=2.40, P<0.001). We propose
that the 9q32 region contains susceptibility locus for cervical cancer and that
TSCOT is a candidate gene potentially involved in the genetic predisposition to
this disease.
PMID- 17035247
TI - Overrepresentation of rare variants in a specific ethnic group may confuse
interpretation of association analyses.
AB - Rare sequence variants may be important in understanding the biology of common
diseases, but clearly establishing their association with disease is often
difficult. Association studies of such variants are becoming increasingly common
as large-scale sequence analysis of candidate genes has become feasible. A recent
report suggested SLITRK1 (Slit and Trk-like 1) as a candidate gene for Tourette
Syndrome (TS). The statistical evidence for this suggestion came from association
analyses of a rare 3'-UTR variant, var321, which was observed in two patients but
not observed in more than 2000 controls. We genotyped 307 Costa Rican and 515
Ashkenazi individuals (TS probands and their parents) and observed var321 in five
independent Ashkenazi parents, two of whom did not transmit this variant to their
affected child. Furthermore, we identified var321 in one subject from an
Ashkenazi control sample. Our findings do not support the previously reported
association and suggest that var321 is overrepresented among Ashkenazi Jews
compared with other populations of European origin. The results further suggest
that overrepresentation of rare variants in a specific ethnic group may
complicate the interpretation of association analyses of such variants,
highlighting the particular importance of precisely matching case and control
populations for association analyses of rare variants.
PMID- 17035248
TI - DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite
outgrowth, is modulated by genetic variations of DISC1.
AB - Disrupted-In-Schizophrenia-1 (DISC1) is a unique susceptibility gene for major
mental conditions, because of the segregation of its genetic variant with
hereditary psychosis in a Scottish pedigree. Genetic association studies
reproducibly suggest involvement of DISC1 in both schizophrenia and bipolar
disorder in several ethnic groups. The DISC1 protein is multifunctional, and a
pool of DISC1 in the dynein motor complex is required for neurite outgrowth in
PC12 cells as well as proper neuronal migration and dendritic arborization in the
developing cerebral cortex in vivo. Here, we show that a specific interaction
between DISC1 and nuclear distribution element-like (NDEL1/NUDEL) is required for
neurite outgrowth in differentiating PC12 cells. Among several components of the
dynein motor complex, DISC1 and NDEL1 are selectively upregulated during neurite
outgrowth upon differentiation in PC12 cells. The NDEL1 binding site of DISC1 was
narrowed down to a small portion of exon 13, corresponding to amino acids 802-835
of DISC1. We demonstrate that genetic variants of DISC1, proximal to the NDEL1
binding site, affect the interaction between DISC1 and NDEL1.
PMID- 17035249
TI - A mutation in the F-box gene, Fbxo11, causes otitis media in the Jeff mouse.
AB - Otitis media (OM), inflammation of the middle ear, is the most common cause of
hearing impairment and surgery in children. Recurrent and chronic forms of OM are
known to have a strong genetic component, but nothing is known of the underlying
genes involved in the human population. We have previously identified a novel
semi-dominant mouse mutant, Jeff, in which the heterozygotes develop chronic
suppurative OM (Hardisty, R.E., Erven, A., Logan, K., Morse, S., Guionaud, S.,
Sancho-Oliver, S., Hunter, A.J., Brown, S.D. and Steel, K.P. (2003) The deaf
mouse mutant Jeff (Jf) is a single gene model of otitis media. J. Assoc. Res.
Otolaryngol., 4, 130-138.) and represent a model for chronic forms of OM in
humans. We demonstrate here that Jeff carries a mutation in an F-box gene,
Fbxo11. Fbxo11 is expressed in epithelial cells of the middle ears from late
embryonic stages through to day 13 of postnatal life. In contrast to Jeff
heterozygotes, Jeff homozygotes show cleft palate, facial clefting and perinatal
lethality. We have also isolated and characterized an additional hypomorphic
mutant allele, Mutt. Mutt heterozygotes do not develop OM but Mutt homozygotes
also show facial clefting and cleft palate abnormalities. FBXO11 is one of the
first molecules to be identified, contributing to the genetic aetiology of OM. In
addition, the recessive effects of mutant alleles of Fbxo11 identify the gene as
an important candidate for cleft palate studies in the human population.
PMID- 17035251
TI - Arterial stiffness: reflections on the arterial pulse.
PMID- 17035250
TI - Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive
cutis laxa.
AB - To elucidate the molecular mechanisms of impaired elastic fiber formation in
recessive cutis laxa, we have investigated two disease-causing missense
substitutions in fibulin-5, C217R and S227P. Pulse-chase immunoprecipitation
experiments indicated that S227P mutant fibulin-5 was synthesized and secreted by
skin fibroblasts at a reduced rate when compared with the wild-type protein. Both
mutants failed to be incorporated into elastic fibers by transfected rat lung
fibroblasts. Purified recombinant fibulin-5 with either mutation showed reduced
affinity for tropoelastin in solid-phase binding assays. Furthermore, S227P
mutant fibulin-5 also showed impaired association with fibrillin-1 microfibrils.
The same mutation triggered an endoplasmic reticulum (ER) stress response, as
indicated by the strong co-localization of this mutant protein with folding
chaperones in the ER, including calreticulin, immunoglobulin-binding protein and
protein disulfide isomerase, and by increased rates of apoptosis in patient
fibroblasts. Histological analysis of skin sections from a cutis laxa patient
with a homozygous S227P mutation showed a lack of fibulin-5 in the extracellular
matrix and a concomitant disorganization of dermal elastic fibers. By electron
microscopy, elastic fibers in the skin of this patient showed a failure of
elastin globules to fuse into a continuous elastic fiber core. We conclude that
recessive cutis laxa mutations in fibulin-5 result in misfolding, decreased
secretion and a reduced interaction with elastin and fibrillin-1 leading to
impaired elastic fiber development. These findings support the hypothesis that
fibulin-5 is necessary for elastic fiber formation by facilitating the deposition
of elastin onto a microfibrillar scaffold via direct molecular interactions.
PMID- 17035252
TI - Assessment of coronary artery stent restenosis by 64-slice multi-detector
computed tomography.
AB - AIMS: We investigated the feasibility of assessing coronary artery stent
restenosis using a new generation 64-slice multi-detector computed tomography
scanner (MDCT) in comparison to conventional quantitative angiography. METHODS
AND RESULTS: MDCT was performed in 64 consecutive patients (mean age 58+/-10
years) with previously implanted coronary artery stents (102 stented lesions:
mean stent diameter 3.17+/-0.38 mm). Each stent was classified as 'evaluable' or
'unevaluable', and in evaluable stents, the presence of in-stent restenosis
(diameter reduction >50%) was determined visually. Results were verified against
invasive, quantitative coronary angiography. Fifty-nine stented lesions (58%)
were classified as evaluable in MDCT. The mean diameter of evaluable stents was
3.28+/-0.40 mm, whereas the mean diameter of non-evaluable stents was 3.03+/-0.31
mm (P=0.0002). Overall, six of 12 in-stent restenoses were correctly detected by
MDCT [50% sensitivity (confidence interval 22-77%)] and in 51 of 90 lesions, in
stent restenosis was correctly ruled out [57% specificity (46-67%)]. In evaluable
stents, six of seven in-stent restenoses were correctly detected, and the absence
of in-stent stenosis was correctly identified in 51 of 52 cases [sensitivity 86%
(42-99%) and specificity 98% (88-100%)]. CONCLUSION: Stent type and diameter
influence evaluability concerning in-stent restenosis by MDCT. The rate of
assessable stents is low, but in evaluable stents, accuracy for detection of in
stent restenosis can be high.
PMID- 17035253
TI - Analysis of myocardial deformation based on ultrasonic pixel tracking to
determine transmurality in chronic myocardial infarction.
AB - AIMS: Pixel tracking-derived myocardial deformation imaging is a new
echocardiographic modality which allows quantitative analysis of segmental
myocardial function on the basis of tracking of natural acoustic markers in 2D
echocardiography. This study evaluated whether myocardial deformation parameters
calculated from 2D echocardiography allow assessment of transmurality of
myocardial infarction as defined by contrast-enhanced cardiac magnetic resonance
imaging (ceMRI). Methods In 47 patients with ischaemic left ventricular
dysfunction, transmurality of myocardial infarction was assessed using pixel
tracking-derived myocardial deformation imaging and ceMRI. For each left
ventricular segment in a 16-segment model, peak systolic radial strain,
circumferential strain, radial strain rate, and circumferential strain rate were
calculated from parasternal 2D echocardiographic views using an automatic frame
by-frame tracking system of natural acoustic echocardiographic markers (EchoPAC,
GE Ultrasound). Myocardial deformation parameters were related to the segmental
extent of hyperenhancement by ceMRI. The relative amount of contrast-enhanced
myocardial tissue per segment was used to define no infarction (0%
hyperenhancement), non-transmural infarction (1-50% hyperenhancement), or
transmural infarction (51-100% hyperenhancement). Results Analysis of myocardial
deformation parameters was possible in 659 segments (88%). Systolic strain and
strain rate parameters decreased with increasing relative hyperenhancement
defined by ceMRI. Radial strain was 27.7+/-8.0, 20.5+/-9.7, and 11.6+/-8.5% for
segments with no infarction (n=422), non-transmural infarction (n=106), and
transmural infarction (n=131), respectively (P<0.0001). Radial strain allowed
distinction of non-transmural infarction from transmural infarction with a
sensitivity of 70.0% and a specificity of 71.2% (cut-off value for radial strain
16.5%). CONCLUSION: Frame-to-frame tracking of acoustic markers in 2D
echocardiographic images for the analysis of myocardial deformation allows
discrimination between different transmurality states of myocardial infarction.
PMID- 17035254
TI - Traffic and the heart.
PMID- 17035255
TI - Satisfaction with life, psychosocial health and materialism among Hungarian
youth.
AB - Previous research suggests that youth's life satisfaction may be influenced by
health and certain socioeconomic/sociocultural factors, which may be important in
a post-socialist country like Hungary. We investigated the relationship between
youth's life satisfaction, materialism and their psychosocial health in a sample
of secondary school students (N = 1114) in Hungary. Findings show that youth's
psychosocial health may play an important role in their levels of life
satisfaction, particularly depressive and psychosomatic symptoms and health
behaviors (e.g. diet control and smoking). SES self-assessment and materialistic
success were positively, while materialistic happiness was negatively related to
youth's life satisfaction.
PMID- 17035256
TI - Negative affect as a mediator between body dissatisfaction and extreme weight
loss and muscle gain behaviors.
AB - Negative affect has been found to mediate the relationship between body
dissatisfaction and bulimia. However, it is unknown if this relationship also
applies to disordered eating, excessive exercise and strategies to increase
muscle for men or women. The aim of this study was to investigate whether
negative and positive affect mediate the relationship between body
dissatisfaction, and these body change strategies. Respondents were 93 men and 97
women (age range: 18-25 years), who completed measures of body dissatisfaction,
positive and negative affect and body change strategies to lose weight or
increase muscles. Body dissatisfaction was associated with strategies to lose
weight, dietary restraint and bulimia for both genders. Negative affect mediated
the relationship between dissatisfaction with muscles and strategies to lose
weight, dietary restraint and bulimia for women only. The results confirm
previous findings related to the association between negative affect and
disordered eating for women. They also demonstrate the need to further
investigate the impact of negative affect on body change strategies, particularly
among men, and those strategies related to increasing muscles.
PMID- 17035257
TI - Experiences of anabolic steroid use: in-depth interviews with men and women body
builders.
AB - This study was designed to investigate anabolic steroid users' experiences of,
and motivations for, use. Five men and six women users took part in in-depth
interviews. Four themes emerged: Steroid Use vs Abuse; Side-effects; Trusted
Information Sources; and Social Pressure. Many users believed that steroids used
in moderation were safe. Serious side-effects (liver and kidney damage,
hypertension) were not significant disincentives. Information from health
professionals tended to be mistrusted because it was not based on first-hand
experience of use. Social support, especially from within the body building
community, was an important motivator. It is concluded that intervention
programmes need the support of the body building community in order to be
effective.
PMID- 17035258
TI - A psychosocial resilience model to account for medical well-being in relation to
sense of coherence.
AB - We tested the suggestion that Sense of Coherence (SOC) may enhance medical well
being by virtue of a favorably balanced profile of psychosocial assets relative
to liabilities. Results derived from a sample of 81 young adults who responded to
a battery of inventories supported the Psychosocial Resilience Model. Our
findings provide preliminary evidence to suggest that a favorable balance between
psychosocial 'protective' and 'risk' factors may, in part, help explain why
people with a strong SOC enjoy high levels of medical well-being.
PMID- 17035259
TI - Attachment, social support and well-being in young and older adults.
AB - The present study examined the link between attachment, social support and well
being in young and older adults. The results from multi-group path analyses
showed significant between-group differences in the links between attachment,
perceived support and well-being. Anxious attachment and well-being were
inversely associated and this was stronger for the younger group than it was for
the older group. Avoidant attachment was negatively related to perceived support
satisfaction in the older age group only, and perceived support mediated the
effects of avoidant attachment on mental health and loneliness in the older
group. Generally, perceived satisfaction with support was more strongly related
with well-being in older adults. The results point to differential links of
insecure attachment styles with perceived support in different life-stages and to
related cognitive, emotional and social processes.
PMID- 17035260
TI - Adult attachment, reassurance seeking and hypochondriacal concerns in college
students.
AB - An individual's attachment style can be conceptualized as a working model for
interactions with others, developed as result of experiences with childhood
caregivers. People with hypochondriacal tendencies are preoccupied with thoughts
of having an illness and constantly seek medical reassurance. We hypothesized
that students with preoccupied attachment would score highly on a measure of
hypochondriasis and investigated whether the association would be explained by
the general tendency to seek reassurance in relationships. A total of 117
undergraduate students completed questionnaires measuring attachment style;
negative affectivity; reassurance seeking in relationships and hypochondriasis.
Participants with preoccupied attachment style (n = 17, 15%) had significantly
higher hypochondriasis scores than those with other attachment styles.
Hierarchical multiple regression analysis suggested that the association between
the preoccupied attachment style and hypochondriasis was explained by the general
tendency to seek reassurance in relationships, with negative affectivity, a
dispositional variable, also acting as a significant predictor of
hypochondriasis.
PMID- 17035261
TI - Examining exercise dependence symptomatology from a self-determination
perspective.
AB - Background Pulling from Self-Determination Theory (SDT; Deci & Ryan, 1985), this
study examined whether individuals classified as 'nondependent-symptomatic' and
'nondependent-asymptomatic' for exercise dependence differed in terms of reported
levels of exercise-related psychological need satisfaction, self-determined
versus controlling motivation and exercise behavior. In addition, we examined the
type of motivational regulations predicting exercise behavior among these
different groups, and their role as mediators between psychological need
satisfaction and behavioral outcomes. Methods Participants (N = 339) completed
measures of exercise-specific psychological need satisfaction, motivational
regulations, exercise behavior and exercise dependence. Results Nondependent
symptomatic individuals reported higher levels of competence need satisfaction
and all forms of motivational regulation, compared to nondependent-asymptomatic
individuals. Introjected regulation approached significance as a positive
predictor of strenuous exercise behavior for symptomatic individuals. Identified
regulation was a positive predictor of strenuous exercise, and completely
mediated the relationship between competence need satisfaction and strenuous
exercise behavior, for asymptomatic individuals. Conclusions The findings
reinforce the applicability of SDT to understanding the quantity and quality of
engagement in exercise.
PMID- 17035262
TI - Preferring proxy-agency: impact on self-efficacy for exercise.
AB - We examined: (a) the social-cognitions of those who differ in preferred level of
proxy-assistance in both proxy-led and independent exercise contexts; and (b) the
relationships between proxy-agency and reliance. Sixty-five fitness class
participants completed measures of self-regulatory efficacy, task self-efficacy,
exercise intentions, proxy-efficacy and perceived reliance. A 2 (exercise
context) by 2 (preferred assistance) MANOVA revealed significant main effects for
assistance and context. Also, significant assistance by context interactions was
found for both efficacies. When facing exercise without a proxy, individuals
preferring high proxy assistance expressed lower self-regulatory and task self
efficacy. Finally, proxy- and self-regulatory efficacy were shown to be separate
predictors of reliance on a proxy. Results support Bandura's theorizing about the
proxy-led context and its influence on self-regulatory efficacy.
PMID- 17035263
TI - Adherence to chest physiotherapy in adults with cystic fibrosis.
AB - Chest physiotherapy (CP) is seen as a cornerstone of Cystic Fibrosis (CF)
treatment. However, previous studies have suggested that adherence to CP is low.
This study of adults with CF (N = 563) investigated CP adherence and associated
factors. Only 29.5 per cent reported undertaking daily CP. Predictors of
adherence included problems with fitting CP into lifestyle, a perception that CP
does not help, physical consequences of CP, doing exercises instead and doing CP
as and when necessary. These variables accounted for 45 per cent of the variance
in adherence. Content analysis revealed a number of themes related to adherence
to CP. Future studies should explore the benefits of daily CP and attempt to
devise simple interventions to maximize adherence to CP.
PMID- 17035264
TI - Goal processes in relation to goal attainment: predicting health-related quality
of life in myocardial infarction patients.
AB - Goal theory suggests that both goal attainment and psychological processes
concerning goal pursuit can influence a patient's (health-related) quality of
life (HRQL) (e.g. Carver & Scheier, 1999). In the present longitudinal study, 46
MI patients completed questionnaires shortly after hospitalization and four
months later, assessing a health, social and individual goal for the coming year,
goal conflict, goal self-efficacy, goal attainment and HRQL. The results of a
multiple regression analysis suggest that both goal conflict and goal self
efficacy predict goal attainment. Furthermore, goal self-efficacy appeared to be
an independent predictor of physical and social HRQL. Goal attainment had a
medium effect on social HRQL, but its effect was mediated by goal conflict and
goal self-efficacy. A goal theory perspective seems to offer additional insights
into HRQL after an MI.
PMID- 17035265
TI - 'Why I won't eat': patient testimony from 15 anorexics concerning the causes of
their disorder.
AB - The following article describes the reasons given by 15 anorexic patients for
their illness. The patients were asked the following question in an open-ended
interview-'What would you say were the causes of your illness?' In reply detailed
complex narratives were gathered from which a number of themes could be
identified. These included unhappiness, control, being in a downward spiral,
obsession and perfectionism. Most patients, for example explained that they were
unhappy. To address their unhappiness, they adopted a strategy of control over
food. Being able to exert this control gave patients a sense of enjoyment and
pride and enabled them to address their underlying fear that a loss of control
may be just around the corner. This pride persuaded patients to restrict further
their food in the hope they would experience even greater enjoyment. Patients
were thus caught in a dangerous 'spiral' of restriction, weight loss, euphoria
and further food refusal. This spiralling behaviour resulted in many patients
describing their illness as an obsession. Several patients equated this
obsessional behaviour with a perfectionist trait in their personalities. In the
following article, these themes of unhappiness, control, spiral, obsession and
perfectionism, are presented, along with the patient testimony on which each
theme was based.
PMID- 17035267
TI - Is early age-related macular degeneration related to carotid artery stiffness?
The Atherosclerosis Risk in Communities Study.
AB - BACKGROUND/PURPOSE: Atherosclerosis and vascular stiffness have been implicated
in the pathogenesis of age-related macular degeneration (AMD). The association of
carotid artery stiffness, a measure of arterial elasticity reflecting early
atherosclerosis, with early AMD, was examined in this study. METHODS: A
population-based, cross-sectional study of 9954 middle-aged people (age range 51
72 years). The presence of AMD signs was determined from fundus photographs
according to the Wisconsin grading protocol. Carotid arterial stiffness was
measured from high-resolution ultrasonic echo tracking of the left common carotid
artery, and was defined as an adjusted arterial diameter change (AADCmu). A
smaller AADC reflects greater carotid artery stiffness. The associations of pulse
pressure and carotid artery intima-media thickness (IMT) with early AMD signs
were also analysed. RESULTS: In the study population, 454 (4.6%) had early AMD.
The mean (SD) AADC was 403 (127) mu. After adjusting for age, sex, race/centre,
education, cigarette smoking, fasting glucose, lipid profile and inflammatory
markers, a smaller AADC was found to be not associated with early AMD (odds ratio
0.94; 95% confidence interval, 0.71 to 1.25) or its component lesions. Other
measures of arterial stiffness (pulse pressure) and atherosclerosis (carotid IMT)
were also not associated with early AMD. CONCLUSIONS: Carotid artery stiffness
was not associated with signs of early AMD in this middle-aged population. These
data provide no evidence of a link between age-related elastoid changes and early
atherosclerotic processes in the carotid arteries and early AMD.
PMID- 17035268
TI - Viscoelastic shear properties of the fresh porcine lens.
AB - AIM: To determine the viscoelastic properties of the porcine lens METHODS: Linear
viscoelastic shear properties of the stroma of four porcine lenses were measured
within 5 hours post-mortem, using sinusoidal oscillatory shear deformation. The
elastic shear modulus, viscous shear modulus, dynamic viscosity, damping ratio,
and phase shift of the lenses were quantified by a controlled-strain, linear
simple-shear rheometer at frequencies of 10-50 Hz. RESULTS: The mean viscoelastic
properties and their standard deviations across the frequencies examined were:
the elastic shear modulus, G' = 6.2+/-4.0 Pa, the viscous shear modulus, G'' =
19.2+/-2.5 Pa, the dynamic viscosity, eta' = 0.16+/-0.1 Pa x sec, the damping
ratio zeta = 4.06+/-1.25, and the phase shift, delta = 76 degrees +/- 5.6
degrees. CONCLUSIONS: The measured viscoelastic shear properties of the porcine
lens reflect a low dynamic viscosity with a high damping ratio. The porcine lens
is viscoelastic and is more viscous than elastic. The magnitude of the complex
shear modulus of the porcine lens, |G*|, is similar to the shear modulus of the
young human lens. Understanding these viscoelastic properties of the natural lens
may provide guidance in developing a lens substitute capable of accommodation in
the post cataract patient.
PMID- 17035269
TI - Clinical characteristics of Mooren's ulcer in South India.
AB - AIM: To describe the clinical characteristics at presentation of a large cohort
of patients with Mooren's ulcer in South India. METHODS: The medical records of
patients with Mooren's ulcer examined in the cornea clinic at Aravind Eye
Hospital Madurai, Tamil Nadu, India, over a 10-year period were reviewed in this
retrospective observational case series. RESULTS: The cohort contained 242 eyes
of 166 patients. All patients were from South India, and men outnumbered women by
a ratio of 4.7:1. The median and mean ages at presentation were 65 and 61 years,
respectively, with a range of 13-95 years. One eye was affected in 90 of 166
(54%) patients. Visual acuity in the affected eye at presentation ranged from 6/6
to light perception, and was 6/12 or better in 34 of 242 (14%) eyes, between 6/12
and 3/60 in 168 (69%) eyes, and worse than 3/60 in 40 (17%) eyes. Partial
peripheral corneal ulceration was observed in 222 (92%) eyes, complete peripheral
corneal ulceration was observed in 15 (6%) eyes and total corneal ulceration was
observed in 5 (2%) eyes. For those 222 eyes with partial peripheral ulceration,
152 (68%) showed temporal involvement, 129 (58%) showed nasal involvement, 116
(52%) showed inferior involvement and 30 (14%) showed superior involvement.
Perforation was observed in 26 (11%) eyes, and was more common in eyes with
peripheral as compared with total ulceration (p<0.001). Identified risk factors
in the cohort included evidence of prior corneal surgery (22%), corneal trauma
(17%) and corneal infection (2%). CONCLUSIONS: Mooren's ulcer is a rare and
potentially blinding eye condition observed not infrequently in the cornea clinic
at Aravind Eye Hospital. Men are affected more often than women and may present
with either unilateral or bilateral disease. Perforation is observed in
approximately 1 in 10 affected eyes at presentation and occurs most often in the
setting of peripheral ulceration. The occurrence of prior corneal surgery, trauma
or infection in nearly one third of patients supports theories of exposure to
corneal antigen in the pathogenesis of this disorder.
PMID- 17035270
TI - Value of retinal vein pulsation characteristics in predicting increased optic
disc excavation.
AB - BACKGROUND: Retinal vein pulsation is often absent in glaucoma, but can be
induced by applying a graded ophthalmodynamometric force (ODF) to the eye, which
is elevated in glaucoma. AIM: To assess whether ODF has a predictive value in
determining glaucoma progression. METHODS: 75 patients with glaucoma and
suspected glaucoma were examined prospectively in 1996, and then re-examined at a
mean of 82 months later. All subjects had intraocular pressure, visual fields,
stereo optic disc photography and ODF measured on their initial visit. When
venous pulsation was spontaneous, the ODF was said to be 0 g. At re-examination,
central corneal thickness and blood pressure were also measured. Initial and
subsequent optic disc photographs were compared and graded into those that had
increased excavation and those that had remained stable. The relationship between
increased excavation (recorded as a binary response) and the measured variables
was modelled using a multiple mixed effects logistic regression. RESULTS: ODF at
the initial visit was strongly predictive of increased excavation (p = 0.004,
odds ratio 1.16/g, range 0-60 g), with greater predictive value in women than in
men (p = 0.004). Visual field mean deviation was predictive of increased
excavation (p = 0.044), as was optic nerve haemorrhage in association with older
age (p = 0.038). Central corneal thickness was not significantly predictive of
increased excavation (p = 0.074) after having adjusted for other variables.
CONCLUSION: ODF measurement seems to be strongly predictive of the patient's risk
for increased optic disc excavation. This suggests that ODF measurement may have
predictive value in assessing the likelihood of glaucoma progression.
PMID- 17035271
TI - Contrast sensitivity and visual hallucinations in patients referred to a low
vision rehabilitation clinic.
AB - AIM: To examine the association of reported visual hallucinations and measured
visual parameters in adult patients referred for low vision rehabilitation.
METHODS: All patients (N = 225) referred to a low vision rehabilitation clinic
for a calendar year were asked a standardised question about symptoms of formed
visual hallucinations. Best corrected visual acuity and contrast sensitivity
using the Pelli-Robson chart were measured. We conducted multiple logistic
regression analysis of the association between visual hallucinations and visual
parameters. RESULTS: Of the total cohort, 78 (35%) reported visual
hallucinations. Visual acuity and contrast sensitivity were considered in four
quartiles. In multiple logistic regression controlling for contrast sensitivity,
age, gender, report of depression and independence, measured acuity in each of
the poorer three categories (compared to the best) was not associated with
reported hallucinations. Contrast sensitivity in the three poorer quartiles
(compared to the best) was strongly associated with the report of hallucinations
(OR 4.1, CI 1.1, 15.9; OR 10.5, CI 2.6, 42.1; OR 28.1, CI 5.6, 140.9) after
controlling for acuity, age, sex, depression and independence. CONCLUSIONS:
Lowest contrast sensitivity was the strongest predictor of reported
hallucinations after adjusting for visual acuity.
PMID- 17035272
TI - Clinical characterisation and molecular analysis of Wagner syndrome.
AB - AIM: To detail the clinical findings in a British family with molecularly
characterised Wagner syndrome. BACKGROUND: Only in the last year has the specific
genetic defect in Wagner syndrome been identified, and the background literature
of the molecular genetics is outlined. Clinical and laboratory findings in a
second case of Wagner syndrome are included to highlight difficulties that can be
encountered when identifying pathogenic mutations for disorders arising in
complex genes. METHODS: Mutation screening was performed using PCR and RT-PCR.
RESULTS: A heterozygous mutation was found converting the donor splice site of
exon 8 of the chondroitin sulphate proteoglycan 2 (CSPG2). This is the same
mutation that has been reported in the original Wagner pedigree. The main
clinical features of Wagner syndrome are vitreous syneresis, thickening and
incomplete separation of the posterior hyaloid membrane, chorioretinal changes
accompanied by subnormal electroretinographic responses, an ectopic fovea and
early-onset cataract. A clinical feature present in this family, but previously
undescribed, is anterior uveitis without formation of synechiae. Wagner syndrome
has a progressive course, resulting in loss of vision even in the absence of
retinal detachment. CONCLUSION: On a background of considerable confusion
regarding the distinction between Wagner syndrome and predominantly ocular
Stickler syndrome, it is now apparent the that two conditions are both clinically
and genetically distinct. This report summarises the clinical findings in Wagner
syndrome and extends the phenotypic characteristics.
PMID- 17035273
TI - Mechanical energy from intraocular instruments cause emulsification of silicone
oil.
AB - AIM: The complications of intraocular silicone oil include emulsification, which
may lead to vision-threatening disorders such as keratopathy, secondary glaucoma
and retinopathy. The authors study the effect of mechanical energy from surgical
instruments on the emulsification of silicone oil. METHODS: Three different
handpieces (phacofragmentation, phacoemulsification, high-speed vitrectomy) were
placed at the interface of balanced salt solution and silicone oil (1000 and 5000
cst, 200 fluid; Dow Corning). The phacofragmentation handpiece was evaluated over
different ultrasound powers and duration. Emulsification was quantified with
phase-contrast microscopy and manual counting of digital photographs by a masked
examiner. In addition, phacoemulsification was performed in the anterior chamber
of a human ex vivo eye with full-fill silicone oil. RESULTS: Emulsification
increases with higher phacofragmentation power and duration and is greater for
1000 cst silicone oil. Emulsification of silicone oil occurs with
phacoemulsification and high-speed vitrectomy handpieces. CONCLUSIONS: The energy
from surgical handpieces is sufficient to result in silicone oil emulsification.
PMID- 17035274
TI - Adalimumab in the therapy of uveitis in childhood.
AB - PURPOSE: Chronic anterior uveitis in children often takes a serious course.
Despite various immunosuppressive drugs some children do not respond sufficiently
and there is a high risk of them becoming seriously disabled. Anti-TNF alpha
therapy has been shown by our group and others to be mostly ineffective
(Etanercept) or partly effective (Infliximab) with the risk of anaphylactic
reactions. Here we report on 18 young patients treated with Adalimumab (Humira),
a complete humanised anti-TNF alpha antibody. METHODS: We retrospectively
analysed 18 patients, who were treated with Adalimumab (20-40 mg, every 2 weeks,
when ineffective every week); 17 had juvenile idiopathic arthritis, one was
without detectable underlying disease. The age at onset of arthritis varied from
0.5-15 years and for uveitis from 2-19 years. Patients were included when the
previous anti-inflammatory therapy had been ineffective. It consisted of systemic
steroids (n = 18), Cyclosporin A (n = 18), Methotrexate (n = 18), Azathioprine (n
= 12), Mycophenolate mofetil (n = 4), Cyclophosphamide (n = 2), Leflunomide (n =
3), Etanercept (n = 8) and Infliximab (n = 5). The grading for uveitis was: (a)
effective: no relapse or more than two relapses less than before treatment, (b)
mild: one relapse less than before treatment, (c) no response: no change in
relapse rate and (d) worsening: more relapses under treatment than before. The
grading for arthritis (depending on the clinical findings), using three out of
six parameters of the ACR PED Criteria, was: effective, mild, no response,
worsening. RESULTS: For arthritis (n = 16) the response to Adalimumab was
effective in 10 of 16 patients, mild in three patients, three did not respond.
For uveitis (n = 18) Adalimumab was effective in 16, mild in one child, and one
patient did not show any effect. After a very good response initially a shorter
application time had to be used to maintain the good anti-inflammatory effect in
one child. Additional immunosuppressive treatment was used in seven of the
effectively treated children. Due to elevation of liver enzymes in one patient,
who also took MTX, Adalimumab had to be discontinued. No anaphylactic reactions
or increased frequency of infections since start of Adalimumab treatment was
reported. CONCLUSIONS: For our group of children with long lasting disease our
results show that Adalimumab was effective or mildly effective against the
arthritis in 81%, but in uveitis in 88%. While these results regarding arthritis
are comparable with other TNF-alpha blocking drugs (Etanercept), Adalimumab seems
to be much more effective against uveitis than Etanercept. Anaphylactic
reactions, found in a previous study from our group after Infliximab treatment,
were not seen with Adalimumab. The necessary dosage and the treatment period,
which probably have to be defined individually for each patient, remain unclear.
PMID- 17035275
TI - Autologous retinal pigment epithelium-choroid sheet transplantation in age
related macular degeneration: morphological and functional results.
AB - OBJECTIVE: To evaluate the outcome of autologous retinal pigment epithelium (RPE)
choroid sheet transplantation after removal of a subfoveal choroidal
neovascularisation (CNV) in patients with age related macular degeneration (AMD).
METHODS: RPE-choroid sheet transplantation was performed in 10 consecutive
patients with exudative AMD (n = 9) or geographic atrophy (n = 1). After CNV
extraction, an autologous RPE-choroid patch was translocated from the
midperiphery under the macula. Follow-up was between 6 and 12 months. Visual
acuity testing and microperimetry (Nidek-MP1) as well as autofluorescence,
fluorescein and indocyanine green (ICG) angiography were performed and the data
were analysed retrospectively. RESULTS: Visual acuity (logarithm of minimum angel
of resolution) before operation ranged from 0.7 to 1.8 (mean 1.37) and after
operation from 0.4 to 1.6 (mean 1.24). Visual acuity after operation improved in
seven patients (by a mean of 0.26), remained stable in one patient and decreased
in two patients. Microperimetry showed light sensitivity and fixation on the
sheet in five cases. ICG angiography demonstrated perfusion through the RPE
choroid graft in nine patients. Postoperative complications included retinal
detachment (n = 1) and epiretinal membrane formation (n = 2). The patient with
geographic atrophy developed a CNV after surgery. CONCLUSIONS: Autologous RPE
choroid sheet transplantation is feasible and a comparatively safe procedure.
Microperimetry showed fixation and light perception over the graft with a
moderate increase in mean visual acuity.
PMID- 17035276
TI - Clinical features of dysthyroid optic neuropathy: a European Group on Graves'
Orbitopathy (EUGOGO) survey.
AB - BACKGROUND: This study was performed to determine clinical features of dysthyroid
optic neuropathy (DON) across Europe. METHODS: Forty seven patients with DON
presented to seven European centres during one year. Local protocols for thyroid
status, ophthalmic examination and further investigation were used. Each eye was
classified as having definite, equivocal, or no DON. RESULTS: Graves'
hyperthyroidism occurred in the majority; 20% had received radioiodine. Of 94
eyes, 55 had definite and 17 equivocal DON. Median Clinical Activity Score was
4/7 but 25% scored 3 or less, indicating severe inflammation was not essential.
Best corrected visual acuity was 6/9 (Snellen) or worse in 75% of DON eyes.
Colour vision was reduced in 33 eyes, of which all but one had DON. Half of the
DON eyes had normal optic disc appearance. In DON eyes proptosis was > 21 mm
(significant) in 66% and visual fields abnormal in 71%. Orbital imaging showed
apical muscle crowding in 88% of DON patients. Optic nerve stretch and fat
prolapse were infrequently reported. CONCLUSION: Patients with DON may not have
severe proptosis and orbital inflammation. Optic disc swelling, impaired colour
vision and radiological evidence of apical optic nerve compression are the most
useful clinical features in this series.
PMID- 17035277
TI - Risks of relapse in patients with acute anterior uveitis.
AB - AIM: To quantify the rate of recurrence of acute anterior uveitis (AAU), and
evaluate the influence of associated risk factors. METHODS: We retrospectively
reviewed the case notes of 185 patients with acute anterior uveitis, from their
time of presentation to August 2001. The time to the first three recurrences of
AAU from the onset of the disease was recorded, as well as the site of
recurrence. Information regarding risk factors (for example (HLA-B27) status,
spondyloarthropathy (SpA), family history of AAU/SpA and history of non-specific
joint pain) were also collected. RESULTS: Patients were followed up until their
third relapse, or up to the censoring date (August 2001) if less than three
relapses had occurred. The median length of follow-up was 35 months. One hundred
and twenty-two patients (66%) developed at least one relapse and 67 (36%) had
three or more relapses. Kaplan-Meier estimate of median interval between disease
onset and the first relapse was 24 months 95% CI (16 to 34) and between the first
and second relapse was 14 months 95% CI (9 to 22), and was 15 months 95% CI (10
to 25) months between the second and third relapse. Using Cox regression only the
number of previous relapses was significantly associated with the risk of AAU
recurrence. There was no significant association between other reported risk
factors and the risk of relapse, and neither did any risk factor significantly
modify the association between previous relapses and AAU recurrence (p>0.066 for
all interactions). There was a borderline significant difference in survival
according to the laterality pattern of recurrences (ipsilateral, alternate, or
bilateral) with a slightly greater than expected number of events in those with
bilateral recurrence (p = 0.048). CONCLUSION: Patients with previous relapse(s)
of AAU have a greater risk of AAU recurrence compared to those at disease onset
but the risk of recurrence appears not to increase in a dose-response manner with
increasing number of previous relapses. Demographic and extraocular features do
not appear to influence the rate, or risk of recurrence of AAU.
PMID- 17035278
TI - Identification of resident and inflammatory bone marrow derived cells in the
sclera by bone marrow and haematopoietic stem cell transplantation.
AB - AIMS: To characterise bone marrow derived cells in the sclera under normal and
inflammatory conditions, we examined their differentiation after transplantation
from two different sources, bone marrow and haematopoietic stem cells (HSC).
METHODS: Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice
were transplanted into irradiated wild-type mice. At 1 month after
transplantation, mice were sacrificed and their sclera examined by histology,
immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron
microscopy. To investigate bone marrow derived cell recruitment under
inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in
transplanted mice. RESULTS: GFP positive cells were distributed in the entire
sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the
total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)%
(HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c
(+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC
transplantation. Transmission and scanning electron microscopy revealed antigen
presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of
GFP (+) cells developed into the sclera. CONCLUSION: We have provided direct and
novel evidence for the migration of bone marrow and HSC cells into the sclera
differentiating into macrophages and dendritic cells. Vast infiltration of bone
marrow and HSC cells was found to be part of the inflammatory process in EAU.
PMID- 17035279
TI - Photoreceptor mitochondrial oxidative stress in early experimental autoimmune
uveoretinitis.
AB - AIMS: In early S-antigen induced experimental uveitis (EAU), photoreceptor
mitochondrial proteins are nitrated prior to macrophage infiltration of the
retina, suggesting that oxidative stress is an initial event in the development
of EAU. We attempted to detect the oxidative stress and localise it in the EAU
retina. METHODS: Lewis rats were immunised with S-antigen in complete Freund's
adjuvant (CFA). Animals were injected with CFA alone and non-immunised animals
served as controls. Immunised and non-immunised animals were killed on day 5 and
subsequent days. Isolated retinas were processed for inducible nitric oxide
synthase (iNOS), tumour necrosis factor (TNF)alpha, interferon (IFN)gamma,
interleukin (IL)Ialpha and CD28 expression by real time polymerase chain
reaction. In addition, iNOS was colocalised with cytochrome c oxidase on day 5 of
EAU. Oxidative stress was detected by 2', 7'-dichlorodihydrofluorescein diacetate
and localised by a mitochondrial specific marker. Leucocyte and T cell
infiltration in the retina/choroid was evaluated by immunohistochemistry.
RESULTS: The iNOS, TNFalpha, IFNgamma, IL1alpha and CD28 transcripts were
significantly upregulated on day 5 in EAU, and iNOS was colocalised with
cytochrome c oxidase in the photoreceptor mitochondria. Oxidative stress was seen
primarily in the photoreceptor mitochondria. Occasional T cells were present in
the retina at this stage. CONCLUSIONS: During early EAU, mitochondrial oxidative
stress is selectively noted in the photoreceptor inner segments. The oxidative
stress appears to result from iNOS upregulation in the photoreceptor mitochondria
and cytokine generation in the retina by a few antigen specific infiltrating T
cells.
PMID- 17035280
TI - The prevalence of refractive errors among schoolchildren in Dezful, Iran.
AB - AIM: To determine the prevalence of refractive errors among schoolchildren in
urban and rural areas of Dezful County, Iran. METHODS: In a cross-sectional
study, using random cluster sampling, 5721 Dezful schoolchildren were selected
from 39 clusters. The participants in the study totalled 5544; 3673 elementary
and middle school students and 1871 high school students. For the former group,
cycloplegic refraction and for the latter, non-cycloplegic refraction was tested.
In all participants, uncorrected visual acuity and best corrected visual acuity
were determined, and those with a visual acuity of 20/40 or worse, underwent a
complete ophthalmic examination to determine the cause of visual impairment. A
spherical equivalent of -0.5 diopter (D) or worse was defined as myopia, +2.0 D
or more was defined as hyperopia, and a cylinder refraction greater than 0.75 D
was considered astigmatism. RESULTS: The uncorrected visual acuity was 20/40 or
worse in the better eye of 224 schoolchildren (3.8% of participants). This figure
(percentage) was 14 (0.03%) based on their best corrected visual acuity and 96
(1.7%) with their presenting vision. According to results of cycloplegic
refraction, 3.4% (95% confidence interval (CI), 2.5 to 4.4) of the primary and
middle school students were myopic and 16.6% (95% CI, 13.6 to 19.7) were
hyperopic. For high school students, these rates were 2.1% (95% CI, 0.7 to 3.5)
and 33.0% (95% CI, 24.9 to 41.1), respectively, with non-cycloplegic refraction.
In the multivariate logistic regression for primary and middle school students,
myopia was correlated with age (p = 0.030), and hyperopia was correlated with age
(p<0.001) and area of residence (p = 0.007). In high school students, hyperopia
again showed a correlation with their area of residence (p = 0.029). CONCLUSION:
The present study reveals the considerable prevalence rates of refractive errors
among schoolchildren in Dezful County and the high rate of an unmet need for
their correction. Although myopia is not very prevalent, the high rate of
hyperopia in the studied population emphasises its need for attention.
PMID- 17035281
TI - Dacryocystorhinostomy in patients lacking an ipsilateral nasal cavity.
AB - Dacryocystorhinostomy (DCR) remains the surgery of choice for the treatment of
epiphora secondary to nasolacrimal duct (NLD) obstruction. It involves creating a
direct soft-tissue anastomosis between the lacrimal sac and the ipsilateral nasal
cavity, via an osteotomy created by removal of the floor of the lacrimal fossa
and surrounding bone. Successful surgery clearly requires the presence of a nasal
space and absence of this poses a surgical challenge. We describe three patients
with absent nasal cavity on the side of lacrimal obstruction, where DCR was
performed by the creation of an anastomosis between the lacrimal sac and the
contralateral nasal space.
PMID- 17035282
TI - Ocular complications in heart, lung and heart-lung recipients.
AB - AIM: To prospectively assess ocular morbidity and the need for ocular screening
in patients on long term, high dose immunosuppression for the maintenance of
solid organ transplants. METHODS: Dilated ocular examinations were performed on
patients receiving immunosuppression for the maintenance of heart, lung and heart
lung transplants. Patients were examined repeatedly in the post transplant
period. RESULTS: Of the 115 transplant recipients examined 62 (54%) had ocular
findings. The most common findings were cataracts (17% of those examined)
followed by hypertensive change (8%), chorioretinal scarring (5%) and diabetic
retinopathy (3%). One patient developed ocular infective complications following
surgery due to Aspergillus spp. endophthalmitis. 18 patients (16%) were
symptomatic at examination with the most common symptom being blurred vision. The
most common finding in symptomatic patients was cataract with almost a quarter of
patients having posterior subcapsular lens opacity that could be attributed to
steroid therapy. CONCLUSION: Patients had surprising low incidences of ocular
infective complications despite previous reports. It is likely that this is due
to improved immunosuppression regimes and improved monitoring of
immunosuppression in the early post-transplant period. The screening of
asymptomatic individuals following heart, lung or heart-lung transplantation was
not supported by this study.
PMID- 17035283
TI - Accuracy of GDx VCC, HRT I, and clinical assessment of stereoscopic optic nerve
head photographs for diagnosing glaucoma.
AB - AIMS: To determine and compare the accuracy and reproducibility of GDx variable
cornea compensation (VCC) scanning laser polarimetry (SLP) with VCC, Heidelberg
retina tomograph (HRT) I confocal scanning laser ophthalmoscopy (CSLO), and
clinical assessment of stereoscopic optic nerve head (ONH) photographs for
diagnosing glaucoma. METHODS: One eye each of 40 healthy subjects, 48 glaucoma
patients, and six patients with ocular hypertension were measured with SLP-VCC
and CSLO. Simultaneous stereoscopic ONH photographs were also obtained. Sixteen
photographs of healthy and glaucomatous eyes were duplicated for assessing
intraobserver agreement. Four glaucoma specialists, four general
ophthalmologists, four residents in ophthalmology, and four optometrists
classified the ONH photographs as normal or glaucomatous. For SLP-VCC, the nerve
fiber indicator (NFI) was evaluated. For CSLO, the Moorfields regression analysis
(MRA) and the Bathija linear discriminant function (LDF) were used. Sensitivity,
specificity, percentage of correctly classified eyes, and intra- and
interobserver agreement, expressed as kappa (kappa) were calculated. RESULTS: SLP
VCC had the highest diagnostic accuracy, with a sensitivity, specificity, and
overall correct classification of 91.7%, 95.0% and 93.2%, respectively. CSLO,
expressed as Bathija LDF and MRA, had a diagnostic accuracy comparable to
glaucoma specialists and general ophthalmologists with an overall accuracy of
89.8%, 86.4%, 86.7% and 85.2%, respectively. Residents classified the fewest eyes
correctly. Intraobserver agreement for classifying the ONH photographs ranged
between 0.48 (within residents) and 0.78 (within glaucoma specialists). The
interobserver agreement ranged between 0.45 (between residents) and 0.74 (between
glaucoma specialists). The agreement between observers and CSLO MRA (kappa, 0.68)
was statistically significantly higher (p<0.001; paired t-test) than between
observers and SLP-VCC NFI (kappa, 0.60) and CSLO Bathija LDF (kappa, 0.62).
CONCLUSION: Automated analysis of measurements with GDx VCC and HRT had a similar
diagnostic accuracy for glaucoma as classification of stereoscopic ONH
photographs by glaucoma specialists, thus bringing all eye-care professionals to
this desirable level. The intra- and interobserver agreement for ONH analysis was
only moderate to good. We think these imaging techniques may assist clinicians in
diagnosing glaucoma.
PMID- 17035284
TI - Morphological and physiological responses of rice (Oryza sativa) to limited
phosphorus supply in aerated and stagnant solution culture.
AB - BACKGROUND AND AIMS: Rain-fed lowland rice commonly encounters stresses from
fluctuating water regimes and nutrient deficiency. Roots have to acquire both
oxygen and nutrients under adverse conditions while also acclimating to changes
in soil-water regime. This study assessed responses of rice roots to low
phosphorus supply in aerated and stagnant nutrient solution. METHODS: Rice (Oryza
sativa 'Amaroo') was grown in aerated solution with high P (200 micro m) for 14
d, then transferred to high or low (1.6 micro m) P supply in aerated or stagnant
solution for up to 8 d. KEY RESULTS: After only 1 d in stagnant conditions, root
radial oxygen loss (ROL) had decreased by 90 % in subapical zones, whereas near
the tip ROL was maintained. After 4 d in stagnant conditions, maximum root length
was 11 % less, and after 8 d, shoot growth was 25 % less, compared with plants in
aerated solution. The plants in stagnant solution had up to 19 % more
adventitious roots, 24 % greater root porosity and 26 % higher root/shoot ratio.
Rice in low P supply had fewer tillers in both stagnant and aerated conditions.
After 1-2 d in stagnant solution, relative P uptake declined, especially at low P
supply. Aerated roots at low P supply maintained relative P uptake for 4 d, after
which uptake decreased to the same levels as in stagnant solution. CONCLUSIONS:
Roots responded rapidly to oxygen deficiency with decreased ROL in subapical
zones within 1-2 d, indicating induction of a barrier to ROL, and these changes
in ROL occurred at least 2 d before any changes in root morphology, porosity or
anatomy were evident. Relative P uptake also decreased under oxygen deficiency,
showing that a sudden decline in root-zone oxygen adversely affects P nutrition
of rice.
PMID- 17035285
TI - Upper limb pain in primary care: health beliefs, somatic distress, consulting and
patient satisfaction.
AB - BACKGROUND: Beliefs and mental well-being could influence decisions to consult
about upper limb pain and satisfaction with care. OBJECTIVES: To describe beliefs
about upper limb pain in the community and explore associations of beliefs and
mental health with consulting and dissatisfaction. METHODS: Questionnaires were
mailed to 4998 randomly chosen working-aged patients from general practices in
Avon. We asked about upper limb pain, consulting, beliefs about symptoms,
dissatisfaction with care, somatizing tendency (using elements of the Brief
Symptom Inventory) and mental well-being (using the Short-Form 36). Associations
were explored by logistic regression. RESULTS: Among 2632 responders, 1271
reported arm pain during the past 12 months, including 389 consulters. A third or
more of responders felt that arm pain sufferers should avoid physical activity,
that problems would persist beyond 3 months, that a doctor should be seen
straightaway and that neglect could lead to permanent harm. Consulters were
significantly more likely to agree with these statements than other upper limb
pain sufferers. The proportion of consultations attributable to such beliefs was
substantial. Dissatisfaction with care was commoner in those with poor mental
health: the OR for being dissatisfied (worst versus best third of the
distribution) was 3.2 (95% CI 1.2-8.5) for somatizing tendency and 2.4 (95% CI
1.3-4.7) for SF-36 score. Both factors were associated with dissatisfaction about
doctors' sympathy, communication and care in examining. CONCLUSIONS: Negative
beliefs about upper limb pain are common and associated with consulting.
Somatizers and those in poorer mental health tend, subsequently, to feel
dissatisfied with care.
PMID- 17035286
TI - A qualitative study to identify factors influencing COXIB prescribed by family
physicians for musculoskeletal disorders.
AB - INTRODUCTION: Cyclo-oxygenase-2 inhibiting (COXIB) anti-inflammatories have been
the drug class prescribed for a large number of cases of musculoskeletal (MSK)
disorders in Canada over the past 5 years. The Alberta Improvements for MSK
Disorders (AIMS) initiative sought to better understand the COXIB prescribing
situation by funding several studies. The objective of this qualitative study was
to determine the factors underlying primary care physicians' medication
prescribing behaviour during an office visit for an MSK disorder, with particular
emphasis on the prescribing of COXIBs. METHODS: The target respondents were
Alberta primary care physicians chosen from a stratified random sample to meet a
wide range of characteristics. Individual, semi-structured interviews were used
to assess decision pathways in four real cases chosen by the physician. A total
of 19 interviews were conducted and analysed using an analytic inductive
approach. RESULTS: Factors judged as being important to decision pathways in
relation to COXIB prescribing for MSK disease included safety, patient
characteristics, affordability to patients, availability of samples, drug company
marketing practices, habit formation, time contstraints, previous clinical
experience of doctors and/or patient with certain drugs and doctors' perception
of absolute versus relative risk. Interpretation. Most physicians preferentially
prescribed COXIBs subsequent to a complicated, multifactorial, but essentially
patient-centred, decision-making process.
PMID- 17035287
TI - Screening for depression in primary care.
PMID- 17035288
TI - Severity of illness and the use of paracetamol in febrile preschool children; a
case simulation study of parents' assessments.
AB - OBJECTIVE: Misconceptions and exaggerated fear of fever may divert parents'
attention from more predictive symptoms of childhood illness, such as appetite
and level of activity. This study aims at exploring how specific predefined
characteristics of febrile preschool children affected parents' assessment of the
severity of the condition and the perceived need for treatment with paracetamol.
METHODS: Parents judged 24 constructed cases of febrile children with different
levels of fever, appetite and activity, occurring at different times of the day.
For each case they decided whether the child was moderately or severely ill, and
whether or not they would prefer to administer paracetamol. Parents' decision
making was examined by discriminant analyses. RESULTS: Of 466 invited parents,
267 supplied information about their families and 205 accepted to participate in
judging constructed cases of febrile children. A total of 159 parents responded
to all cases. When evaluating the severity of the illness, 119 parents (75%)
responded to one or more of the four cues describing illness. Only one of four
cues was used by 80 parents (67%), and 86 (72%) parents emphasized fever. When
deciding to give paracetamol, one or more of four cues was used by 102 parents
(64%), while 72 parents (71%) used only one cue, and 92 parents (90%) emphasized
fever. CONCLUSIONS: Parents focus on fever when they evaluate febrile illness and
decide whether or not to give paracetamol. Educating parents to focus on their
child's level of appetite or activity may improve management, especially when
judgement is based on only one or two cues.
PMID- 17035289
TI - Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis.
AB - We here report essential roles of the Bmp-binding protein crossveinless 2 (Cv2;
Bmper) in mouse organogenesis. In the null Cv2 mutant mouse, gastrulation occurs
normally, but a number of defects are found in Cv2-expressing tissues such as the
skeleton. Cartilage differentiation by Bmp4 treatment is reduced in cultured Cv2(
/-) fibroblasts. Moreover, the defects in the vertebral column and eyes of the
Cv2(-/-) mouse are substantially enhanced by deleting one copy of the Bmp4 gene,
suggesting a pro-Bmp role of Cv2 in the development of these organs. In addition,
the Cv2(-/-) mutant exhibits substantial defects in Bmp-dependent processes of
internal organ formation, such as nephron generation in the kidney. This kidney
hypoplasia is synergistically enhanced by the additional deletion of Kcp (Crim2)
which encodes a pro-Bmp protein structurally related to Cv2. This study
demonstrates essential pro-Bmp functions of Cv2 for locally restricted signal
enhancement in multiple aspects of mammalian organogenesis.
PMID- 17035290
TI - Jagged 1 is a beta-catenin target gene required for ectopic hair follicle
formation in adult epidermis.
AB - The Wnt and Notch signalling pathways regulate hair follicle maintenance, but how
they intersect is unknown. We show that Notch signalling is active in the hair
follicle pre-cortex, a region of high Wnt activity, where commitment to hair
lineages occurs. Deletion of jagged 1 (Jag1) results in inhibition of the hair
growth cycle and conversion of hair follicles into cysts of cells undergoing
interfollicular epidermal differentiation. Conversely, activation of Notch in
adult epidermis triggers expansion of the base of the hair follicle, sebaceous
gland enlargement and abnormal clumping of the follicles. In adult epidermis, the
induction of new hair follicle formation by beta-catenin is prevented by blocking
Notch signalling pharmacologically or through Jag1 deletion. Conversely,
activation of both pathways accelerates growth and differentiation of ectopic
follicles. beta-catenin stimulates Notch signalling by inducing Jag1
transcription. We conclude that the Notch pathway acts downstream of the Wnt/beta
catenin pathway to determine epidermal cell fate.
PMID- 17035291
TI - Uncoupling dorsal-mediated activation from dorsal-mediated repression in the
Drosophila embryo.
AB - The Rel family transcription factor Dorsal patterns the dorsoventral axis of the
Drosophila embryo by activating genes such as twist and snail and repressing
genes such as decapentaplegic and zerknullt. Dorsal represses transcription by
recruiting the co-repressor Groucho. However, repression occurs only when Dorsal
binding sites are close to binding sites for other factors that also bind
Groucho. The need for additional factors to assist Dorsal in repression may
result from the intrinsically weak interaction between Dorsal and Groucho. To
test this idea, we generated a Dorsal variant containing a high-affinity Groucho
recruitment motif at its C terminus. As predicted, this variant functions as a
dedicated repressor, silencing decapentaplegic and zerknullt while failing to
activate twist and snail. We also converted Dorsal into a dedicated activator by
replacing its weak Groucho-recruitment motif with heterologous activation
domains. Although the dedicated activator alleles fail to repress decapentaplegic
and zerknullt in the syncytial blastoderm embryo, they are able to pattern the
dorsoventral axis. This indicates that dorsoventral patterning is not dependent
upon Dorsal-mediated repression, reflecting the existence of redundant mechanisms
to block Decapentaplegic signaling.
PMID- 17035292
TI - Genetic analysis of EphA-dependent signaling mechanisms controlling topographic
mapping in vivo.
AB - Ephrin/Eph ligands and receptors are best known for their prominent role in
topographic mapping of neural connectivity. Despite the large amount of work
centered on ephrin/Eph-dependent signaling pathways in various cellular contexts,
the molecular mechanisms of action of Eph receptors in neural mapping, requiring
dynamic interactions between complementary gradients of ephrins and Eph
receptors, remain largely unknown. Here, we investigated in vivo the signaling
mechanisms of neural mapping mediated by the EphA4 receptor, previously shown to
control topographic specificity of thalamocortical axons in the mouse
somatosensory system. Using axon tracing analyses of knock-in mouse lines
displaying selective mutations for the Epha4 gene, we determined for the first
time which intracellular domains of an Eph receptor are required for topographic
mapping. We provide direct in vivo evidence that the tyrosine kinase domain of
EphA4, as well as a tight regulation of its activity, are required for
topographic mapping of thalamocortical axons, whereas non-catalytic functional
modules, such as the PDZ-binding motif (PBM) and the Sterile-alpha motif (SAM)
domain, are dispensable. These data provide a novel insight into the molecular
mechanisms of topographic mapping, and constitute a physiological framework for
the dissection of the downstream signaling cascades involved.
PMID- 17035293
TI - DNA supercoiling factor contributes to dosage compensation in Drosophila.
AB - DNA supercoiling factor (SCF) is a protein capable of generating negative
supercoils in DNA in conjunction with topoisomerase II. To clarify the biological
functions of SCF, we introduced a heritable SCF RNAi into Drosophila. Upon
knockdown of SCF, we observed male lethality and male-specific reduction in the
expression levels of X-linked genes. SCF functionally interacts with components
of the MSL complex, which are required for dosage compensation via
hypertranscription of the male X chromosome. Moreover, SCF colocalizes with the
MSL complex along the male X chromosome. Upon overexpression of SCF, the male X
chromosome had a bloated appearance. This phenotype was dependent on the histone
acetyltransferase MOF and was suppressed by simultaneous overexpression of ISWI.
These findings demonstrate that SCF plays a role in transcriptional activation
via alteration of chromatin structure and provide evidence that SCF contributes
to dosage compensation.
PMID- 17035294
TI - Compartments and the control of growth in the Drosophila wing imaginal disc.
AB - The mechanisms that control organ growth are among the least known in
development. This is particularly the case for the process in which growth is
arrested once final size is reached. We have studied this problem in the wing
disc of Drosophila, the developmental and growth parameters of which are well
known. We have devised a method to generate entire fast-growing Minute(+) (M(+))
discs or compartments in slow developing Minute/+ (M/+) larvae. Under these
conditions, a M(+) wing disc gains at least 20 hours of additional development
time. Yet it grows to the same size of Minute/+ discs developing in M/+ larvae.
We have also generated wing discs in which all the cells in either the anterior
(A) or the posterior (P) compartment are transformed from M/+ to M(+). We find
that the difference in the cell division rate of their cells is reflected in
autonomous differences in the developmental progression of these compartments:
each grows at its own rate and manifests autonomous regulation in the expression
of the developmental genes wingless and vestigial. In spite of these differences,
;mosaic' discs comprising fast and slow compartments differentiate into adult
wings of the correct size and shape. Our results demonstrate that imaginal discs
possess an autonomous mechanism with which to arrest growth in anterior and
posterior compartments, which behave as independent developmental units. We
propose that this mechanism does not act by preventing cell divisions, but by
lengthening the division cycle.
PMID- 17035295
TI - Frizzled/RYK mediated signalling in axon guidance.
PMID- 17035296
TI - Toronto's Health Department in action: influenza in 1918 and SARS in 2003.
AB - This article compares the Toronto Health Department's role in controlling the
1918 influenza epidemic with its activities during the SARS outbreak in 2003 and
concludes that local health departments are the foundation for successful disease
containment, provided that there is effective coordination, communication, and
capacity. In 1918, Toronto's MOH Charles Hastings was the acknowledged leader of
efforts to contain the disease, care for the sick, and develop an effective
vaccine, because neither a federal health department nor an international body
like WHO existed. During the SARS outbreak, Hastings's successor, Sheela Basrur,
discovered that nearly a decade of underfunding and new policy foci such as
health promotion had left the department vulnerable when faced with a potential
epidemic. Lack of cooperation by provincial and federal authorities added further
difficulties to the challenge of organizing contact tracing, quarantine, and
isolation for suspected and probable cases and providing information and
reassurance to the multi-ethnic population. With growing concern about a flu
pandemic, the lessons of the past provide a foundation for future communicable
disease control activities.
PMID- 17035297
TI - Mechanisms of endothelial cell protection by blockade of the JAK2 pathway.
AB - Inhibition of the JAK2/STAT pathway has been implicated recently in
cytoprotective mechanisms in both vascular smooth muscle cells and astrocytes.
The advent of JAK2-specific inhibitors provides a practical tool for the study of
this pathway in different cellular types. An interest in finding methods to
improve endothelial cell (EC) resistance to injury led us to examine the effect
of JAK2/STAT inhibition on EC protection. Furthermore, the signaling pathways
involved in JAK2/STAT inhibition-related actions were examined. Our results
reveal, for the first time, that blockade of JAK2 with the tyrosine kinase
inhibitor AG490 strongly protects cultured EC against cell detachment-dependent
death and serum deprivation and increases reseeding efficiency. Confirmation of
the specificity of the effects of JAK2 inhibition was attained by finding
protective effects on transfection with a dominant negative JAK2. Furthermore,
AG490 blocked serum deprivation-induced phosphorylation of JAK2. In terms of
mechanism, treatment with AG490 induces several relevant responses, both in
monolayer and detached cells. These mechanisms include the following: 1) Increase
and nuclear translocation of the active, dephosphorylated form of beta-catenin.
In functional terms, this translocation is transcriptionally active, and its
protective effect is further supported by the stimulation of EC cytoprotection by
transfectionally induced excess of beta-catenin. 2) Increase of platelet
endothelial cell adhesion molecule (PECAM)/CD31 levels. 3) Increase in total and
phosphorylated AKT. 4) Increase in phosphorylated glycogen synthase kinase
(GSK)3alpha/beta. The present findings imply potential practical applications of
JAK2 inhibition on EC. These applications affect not only EC in the monolayer but
also circulating detached cells and involve mechanistic interactions not
previously described.
PMID- 17035298
TI - Biologically active lipids promote trafficking and membrane association of Rac1
in insulin-secreting INS 832/13 cells.
AB - Despite emerging evidence to suggest that glucose-stimulated insulin secretion
(GSIS) requires membrane targeting of specific small G proteins (e.g., Rac1),
very little is known with regard to the precise mechanisms underlying subcellular
trafficking of these proteins in the glucose-stimulated islet beta-cell. We
previously reported activation of small G proteins by biologically active lipids
via potentiation of relevant GDP/GTP exchange activities within the beta-cell.
Herein, we studied putative regulatory roles for these lipids in the trafficking
and membrane association of Rac1 in cell-free preparations derived from INS
832/13 beta-cells. Incubation of INS 832/13 cell lysates with
polyphosphoinositides (e.g., PIP(2)), phosphatidic acid, phosphatidylcholine, and
phosphatidylserine significantly promoted trafficking of cytosolic Rac1 to the
membrane fraction. Lysophosphatidic acid, but not lysophosphatidylcholine or
lysophosphatidylserine, also promoted translocation and membrane association of
Rac1. Arachidonic acid, diacylglycerol, calcium, and cAMP failed to exert any
clear effects on Rac1 translocation to the membrane. Together, our findings
provide the first direct evidence in support of our recent hypothesis (Kowluru A,
Veluthakal R. Diabetes 54: 3523-3529, 2005), which states that generation of
biologically active lipids, known to occur in the glucose-stimulated beta-cell,
may mediate targeting of Rac1 to the membrane for optimal interaction with its
putative effector proteins leading to GSIS.
PMID- 17035299
TI - Role of Na+-K+-Cl- cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction
in astrocytes following in vitro ischemia.
AB - Na(+)-K(+)-Cl(-) cotransporter isoform 1 (NKCC1) and reverse mode operation of
the Na(+)/Ca(2+) exchanger (NCX) contribute to intracellular Na(+) and Ca(2+)
overload in astrocytes following oxygen-glucose deprivation (OGD) and
reoxygenation (REOX). Here, we further investigated whether NKCC1 and NCX play a
role in mitochondrial Ca(2+) (Ca(m)(2+)) overload and dysfunction. OGD/REOX
caused a doubling of mitochondrial-releasable Ca(2+) (P < 0.05). When NKCC1 was
inhibited with bumetanide, the mitochondrial-releasable Ca(2+) was reduced by
approximately 42% (P < 0.05). Genetic ablation of NKCC1 also reduced Ca(m)(2+)
accumulation. Moreover, OGD/REOX in NKCC1(+/+) astrocytes caused dissipation of
the mitochondrial membrane potential (Psi(m)) to 42 +/- 3% of controls. In
contrast, when NKCC1 was inhibited with bumetanide, depolarization of Psi(m) was
attenuated significantly (66 +/- 10% of controls, P < 0.05). Cells were also
subjected to severe in vitro hypoxia by superfusion with a hypoxic, acidic, ion
shifted Ringer buffer (HAIR). HAIR/REOX triggered a secondary, sustained rise in
intracellular Ca(2+) that was attenuated by reversal NCX inhibitor KB-R7943. The
hypoxia-mediated increase in Ca(m)(2+) was accompanied by loss of Psi(m) and
cytochrome c release in NKCC1(+/+) astrocytes. Bumetanide or genetic ablation of
NKCC1 attenuated mitochondrial dysfunction and astrocyte death following
ischemia. Our study suggests that NKCC1 acting in concert with NCX causes a
perturbation of Ca(m)(2+) homeostasis and mitochondrial dysfunction and cell
death following in vitro ischemia.
PMID- 17035300
TI - Kinetics of integrated electron transfer in the mitochondrial respiratory chain:
random collisions vs. solid state electron channeling.
AB - Recent evidence, mainly based on native electrophoresis, has suggested that the
mitochondrial respiratory chain is organized in the form of supercomplexes, due
to the aggregation of the main respiratory chain enzymatic complexes. This
evidence strongly contrasts the previously accepted model, the Random Diffusion
Model, largely based on kinetic studies, stating that the complexes are randomly
distributed in the lipid bilayer of the inner membrane and functionally connected
by lateral diffusion of small redox molecules, i.e., coenzyme Q and cytochrome c.
This review critically examines the experimental evidence, both structural and
functional, pertaining to the two models and attempts to provide an updated view
of the organization of the respiratory chain and of its kinetic consequences. The
conclusion that structural respiratory assemblies exist is overwhelming, whereas
the expected functional consequence of substrate channeling between the assembled
enzymes is controversial. Examination of the available evidence suggests that,
although the supercomplexes are structurally stable, their kinetic competence in
substrate channeling is more labile and may depend on the system under
investigation and the assay conditions.
PMID- 17035301
TI - VOCCs and TREK-1 ion channel expression in human tenocytes.
AB - Mechanosensitive and voltage-gated ion channels are known to perform important
roles in mechanotransduction in a number of connective tissues, including bone
and muscle. It is hypothesized that voltage-gated and mechanosensitive ion
channels also may play a key role in some or all initial responses of human
tenocytes to mechanical stimulation. However, to date there has been no direct
investigation of ion channel expression by human tenocytes. Human tenocytes were
cultured from patellar tendon samples harvested from five patients undergoing
routine total knee replacement surgery (mean age: 66 yr; range: 63-73 yr). RT
PCR, Western blotting, and whole cell electrophysiological studies were performed
to investigate the expression of different classes of ion channels within
tenocytes. Human tenocytes expressed mRNA and protein encoding voltage-operated
calcium channel (VOCC) subunits (Ca alpha(1A), Ca alpha(1C), Ca alpha(1D), Ca
alpha(2)delta(1)) and the mechanosensitive tandem pore domain potassium channel
(2PK(+)) TREK-1. They exhibit whole cell currents consistent with the functional
expression of these channels. In addition, other ionic currents were detected
within tenocytes consistent with the expression of a diverse array of other ion
channels. VOCCs and TREK channels have been implicated in mechanotransduction
signaling pathways in numerous connective tissue cell types. These mechanisms may
be present in human tenocytes. In addition, human tenocytes may express other
channel currents. Ion channels may represent potential targets for the
pharmacological management of chronic tendinopathies.
PMID- 17035302
TI - Actin-based features negatively regulated by protein kinase C-epsilon.
AB - Cells exposed to phorbol 12-myristate 13-acetate (PMA) undergo a choreographed
sequence of morphological changes. Some of these, including stimulation of
membrane ruffles and the later appearance of stress fibers, rely on remodeling of
the actin cytoskeleton. Although this process is poorly understood, it is
important, because the same features are affected during oncogenic
transformation. PMA also activates protein kinase C (PKC). Enzyme activation is
followed by degradation. Either process might affect the remodeling of actin. The
present studies determined whether any PKC isozymes were subject to degradation
in tracheal epithelial cells by quantifying the amount of each isozyme present
after PMA exposure. PKC-epsilon was the only isozyme to show declining content
correlated with increased stress fiber accumulation. Stress fibers increased
between 5 and 10 h, whereas PKC-epsilon declined to 38% of its starting value
(95% confidence interval, 10-68%). The relationship could be fit by the function
F(x) = 0.683 x exp[-0.841(x - 0.387)], where F is the frequency of fiber
containing cells and x is PKC-epsilon content. Fiber accumulation was further
investigated after knockdown of PKC-epsilon with RNA interference and antisense
oligodeoxynucleotide. Knockdown enhanced stress fibers in cells not yet exposed
to PMA as well as the final frequency of fiber-containing cells after PMA
exposure. With knockdown at both transcriptional and protein levels,
approximately 15% of the original content was predicted and achieved, as judged
from real-time PCR and PKC-epsilon content measurements. The results suggest that
PKC-epsilon negatively regulates stress fibers, either by directly turning over
one of their components or by regulating an upstream step affecting fiber
organization.
PMID- 17035303
TI - Dynamics of clathrin and adaptor proteins during endocytosis.
AB - The endocytic adaptor complex AP-2 colocalizes with the majority of clathrin
positive spots at the cell surface. However, we previously observed that AP-2 is
excluded from internalizing clathrin-coated vesicles (CCVs). The present studies
quantitatively demonstrate that AP-2 disengages from sites of endocytosis seconds
before internalization of the nascent CCV. In contrast, epsin, an alternate
adaptor for clathrin at the plasma membrane, disappeared, along with clathrin.
This suggests that epsin remains an integral part of the CCV throughout
endocytosis. Clathrin spots at the cell surface represent a heterogeneous
population: a majority (70%) of the spots disappeared with a time course of 4
min, whereas a minority (22%) remained static for > or =30 min. The static
clathrin spots undergo constant subunit exchange, suggesting that although they
are static structures, these spots comprise functional clathrin molecules, rather
than dead-end aggregates. These results support a model where AP-2 serves a cargo
sorting function before endocytosis, whereas alternate adaptors, such as epsin,
actually link cargo to the clathrin coat surrounding nascent endocytic vesicles.
These data also support a role for static clathrin, providing a nucleation site
for endocytosis.
PMID- 17035304
TI - Occurrence of a nonsulfated chondroitin proteoglycan in the dried saliva of
Collocalia swiftlets (edible bird's-nest).
AB - Despite their wide occurrence, proteoglycans (PGs) have never been isolated from
the saliva of higher animals. We found that the Collocalia glycoproteins isolated
from edible birds'-nests (the dried forms of regurgitated saliva of male
Collocalia swiftlets) were rich in a PG containing nonsulfated chondroitin
glycosaminoglycans (GAGs). We have devised a method to isolate a PG from the
water extract of the white nest built by Aerodramus fuciphagus (white nest
swiftlets) with a yield of 2-mg PG per gram nest. This PG contained 83% of
carbohydrates, of which 79% were GalNAc and GlcUA (D-glucuronic acid) in an
equimolar ratio. By using chondroitin AC lyase, the structure of GAGs in this PG
was established to be chondroitin ( --> 4GlcUAbeta1 --> 3GalNAcbeta1 --> )(n)
chains. The average molecular mass of the chondroitin chain was estimated to be
49 kDa by gel filtration. We have isolated a linkage region hexasaccharide,
DeltaHexUAalpha1 --> 3GalNAcbeta1 --> 4GlcUAbeta1 --> 3Galbeta1 --> 3Galbeta1 -->
4Xyl, from this PG by chondroitinase ABC digestion to show that the GAGs in this
PG are also linked to the core protein through the common tetrasaccharide linker,
GlcUAbeta1 --> 3Galbeta1 --> 3Galbeta1 --> 4Xyl, found in various PGs. As water
was not effective in extracting uronic acid-containing glycoconjugates from the
black nest built by black nest swiftlets (A. maximus), we used 4 M guanidium
chloride and anion-exchange chromatography in the presence of urea to extract and
isolate about 30 mg of a chondroitin PG preparation from 10 g of the desialylated
black nest. As the biological significance of chondroitin is still not well
understood, bird's nest should become a convenient source for preparing this
unique GAG to study its biological functions.
PMID- 17035305
TI - Examination of a fusogenic hexameric core from human metapneumovirus and
identification of a potent synthetic peptide inhibitor from the heptad repeat 1
region.
AB - Paramyxoviruses are a leading cause of childhood illness worldwide. A recently
discovered paramyxovirus, human metapneumovirus (hMPV), has been studied by our
group in order to determine the structural relevance of its fusion (F) protein to
other well-characterized viruses utilizing type I integral membrane proteins as
fusion aids. Sequence analysis and homology models suggested the presence of
requisite heptad repeat (HR) regions. Synthetic peptides from HR regions 1 and 2
(HR-1 and -2, respectively) were induced to form a thermostable (melting
temperature, approximately 90 degrees C) helical structure consistent in mass
with a hexameric coiled coil. Inhibitory studies of hMPV HR-1 and -2 indicated
that the synthetic HR-1 peptide was a significant fusion inhibitor with a 50%
inhibitory concentration and a 50% effective concentration of approximately 50
nM. Many viral fusion proteins are type I integral membrane proteins utilizing
the formation of a hexameric coiled coil of HR peptides as a major driving force
for fusion. Our studies provide evidence that hMPV also uses a coiled-coil
structure as a major player in the fusion process. Additionally, viral HR-1
peptide sequences may need further investigation as potent fusion inhibitors.
PMID- 17035306
TI - Regulation of CXCL-8 (interleukin-8) induction by double-stranded RNA signaling
pathways during hepatitis C virus infection.
AB - Hepatitis C virus (HCV) infection induces the alpha-chemokine interleukin-8 (CXCL
8), which is regulated at the levels of transcription and mRNA stability. In the
current study, CXCL-8 regulation by double-stranded (ds)RNA pathways was analyzed
in the context of HCV infection. A constitutively active mutant of the retinoic
acid-inducible gene I (RIG-I), RIG-N, activated CXCL-8 transcription. Promoter
mutagenesis experiments indicated that NF-kappaB and interferon (IFN)-stimulated
response element (ISRE) binding sites were required for the RIG-N induction of
CXCL-8 transcription. IFN-beta promoter stimulator 1 (IPS-1) expression also
activated CXCL-8 transcription, and mutations of the ISRE and NF-kappaB binding
sites reduced and abrogated CXCL-8 transcription, respectively. In the presence
of wild-type RIG-I, transfection of JFH-1 RNA or JFH-1 virus infection of
Huh7.5.1 cells activated the CXCL-8 promoter. Expression of IFN regulatory factor
3 (IRF-3) stimulated transcription from both full-length and ISRE-driven CXCL-8
promoters. Chromatin immunoprecipitation assays demonstrated that IRF-3 and NF
kappaB bound directly to the CXCL-8 promoter in response to virus infection and
dsRNA transfection. RIG-N stabilized CXCL-8 mRNA via the AU-rich element in the
3' untranslated region of CXCL-8 mRNA, leading to an increase in its half-life
following tumor necrosis factor alpha induction. The data indicate that HCV
infection triggers dsRNA signaling pathways that induce CXCL-8 via
transcriptional activation and mRNA stabilization and define a regulatory link
between innate antiviral and inflammatory cellular responses to virus infection.
PMID- 17035307
TI - Role for nonstructural protein 1 of severe acute respiratory syndrome coronavirus
in chemokine dysregulation.
AB - Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused
by a novel coronavirus. Since its associated morbidity and mortality have been
postulated to be due to immune dysregulation, we investigated which of the viral
proteins is responsible for chemokine overexpression. To delineate the viral and
cellular factor interactions, the role of four SARS coronavirus proteins,
including nonstructural protein 1 (nsp-1), nsp-5, envelope, and membrane, were
examined in terms of cytokine induction. Our results showed that the SARS
coronavirus nsp-1 plays an important role in CCL5, CXCL10, and CCL3 expression in
human lung epithelial cells via the activation of NF-kappaB.
PMID- 17035308
TI - NKG2C+ NK cells are enriched in AIDS patients with advanced-stage Kaposi's
sarcoma.
AB - Kaposi's sarcoma (KS) is an AIDS-defining condition in individuals with human
immunodeficiency virus type 1 infection. We investigated the phenotype and
function of the NKG2C+ NK cell population in individuals with AIDS and Kaposi's
sarcoma. The staging of AIDS KS patients according to the AIDS Clinical Trial
Group criteria revealed that patients with the S1 disease stage have a
significantly higher proportion of NKG2C+ cells than those with the S0 disease
stage. NKG2C+ cells from S1-stage patients are highly enriched for the expression
of KIR3DL1, are depleted of NKp46, and respond poorly to major histocompatibility
complex class I-positive target cells. These data demonstrate a link between NK
cell phenotype and function and disease prognosis in AIDS.
PMID- 17035309
TI - Nucleocytoplasmic shuttling of bovine papillomavirus E1 helicase downregulates
viral DNA replication in S phase.
AB - The papillomavirus E1 protein is essential for the initiation of viral
replication. We previously showed that the bovine papillomavirus E1 protein is
unstable and becomes resistant to ubiquitin-mediated degradation when tightly
bound to cyclin E-cyclin-dependent kinase 2 (Cdk2) before the start of DNA
synthesis. However, neither the protection nor the targeted degradation of E1
appears to depend on its phosphorylation by Cdk. Here, we report that Cdk
phosphorylation of E1 is also not a prerequisite for the initiation of viral DNA
replication either in vitro or in vivo. Nevertheless, we found that
phosphorylation of one Cdk site, Ser283, abrogates E1 replicative activity only
in a cellular context. We show that this site-specific phosphorylation of E1
drives its export from the nucleus and promotes its continuous nucleocytoplasmic
shuttling. In addition, we find that E1 shuttling occurs in S phase, when cyclin
A-Cdk2 is activated. E1 interacts with the active cyclin A-Cdk2 complex and is
phosphorylated on Ser283 by this kinase. These data suggest that the
phosphorylation of E1 on Ser283 is a negative regulatory event that is involved
in preventing the amplification of viral DNA during S phase. This finding reveals
a novel facet of E1 regulation that could account for the variations of the viral
replication capacity during different cell cycle phases, as well as in different
stages of the viral cycle.
PMID- 17035310
TI - Mathematical modeling of subgenomic hepatitis C virus replication in Huh-7 cells.
AB - Cell-based hepatitis C virus (HCV) replicon systems have provided a means for
understanding HCV replication mechanisms and for testing new antiviral agents. We
describe here a mathematical model of HCV replication that assumes that the
translation of the HCV polyprotein occurs in the cytoplasm, that HCV RNA
synthesis occurs in vesicular-membrane structures, and that the strategy of
replication involves a double-stranded RNA intermediate. Our results shed light
on the intracellular dynamics of subgenomic HCV RNA replication from transfection
to steady state within Huh-7 cells. We predict the following: (i) about 6 x 10(3)
ribosomes are involved in generating millions of HCV NS5B-polymerase molecules in
a Huh-7 cell, (ii) the observed 10:1 asymmetry of plus- to minus-strand RNA
levels can be explained by a higher-affinity (200-fold) interaction of HCV NS5B
polymerase-containing replication complexes with HCV minus-strand RNA over HCV
plus-strand RNA in order to initiate synthesis, (iii) the latter higher affinity
can also account for the observed approximately 6:1 plus-strand/minus-strand
ratio in vesicular-membrane structures, and (iv) the introduction of higher
numbers of HCV plus-strand RNA by transfection leads to faster attainment of
steady-state but does not change the steady-state HCV RNA level. Fully permissive
HCV replication systems have been developed, and the model presented here is a
first step toward building a comprehensive model for complete HCV replication.
Moreover, the model can serve as an important tool in understanding HCV
replication mechanisms and should prove useful in designing and evaluating new
antivirals against HCV.
PMID- 17035311
TI - Epstein-barr virus-induced resistance to drugs that activate the mitotic spindle
assembly checkpoint in Burkitt's lymphoma cells.
AB - Epstein-Barr virus (EBV) is associated with a number of human cancers, and latent
EBV gene expression has been reported to interfere with cell cycle checkpoints
and cell death pathways. Here we show that latent EBV can compromise the mitotic
spindle assembly checkpoint and rescue Burkitt's lymphoma (BL)-derived cells from
caspase-dependent cell death initiated in aberrant mitosis. This leads to
unscheduled mitotic progression, resulting in polyploidy and multi- and/or
micronucleation. The EBV latent genes responsible for this phenotype are
expressed from the P3HR1 strain of virus and several viruses with similar genomic
deletions that remove the EBNA2 gene. Although EBNA2 and the latent membrane
proteins are not expressed, the EBNA3 proteins are present in these BL cells.
Survival of the EBV-positive cells is not consistently associated with EBV lytic
gene expression or with the genes that are expressed in EBV latency I BL cells
(i.e., EBNA1, EBERs, and BARTs) but correlates with reduced expression of the
cellular proapoptotic BH3-only protein Bim. These data suggest that a subset of
latent EBV gene products may increase the likelihood of damaged DNA being
inherited because of the impaired checkpoint and enhanced survival capacity. This
could lead to greater genetic diversity in progeny cells and contribute to
tumorigenesis. Furthermore, since it appears that this restricted latent EBV
expression interferes with the responses of Burkitt's lymphoma-derived cells to
cytotoxic drugs, the results of this study may have important therapeutic
implications in the treatment of some BL.
PMID- 17035312
TI - Wild-type levels of human immunodeficiency virus type 1 infectivity in the
absence of cellular emerin protein.
AB - Preintegration complexes (PICs) mediate retroviral integration, and recent
results indicate an important role for the inner nuclear membrane protein emerin
in orienting human immunodeficiency virus type 1 (HIV-1) PICs to chromatin for
integration. Two other host cell proteins, the barrier-to-autointegration factor
(BAF) and lamina-associated polypeptide 2alpha (LAP2alpha), seemed to play a
similar preintegrative role for Moloney murine leukemia virus (MMLV) in addition
to HIV-1. In contrast, we determined efficient HIV-1 and MMLV infection of HeLa
P4 cells following potent down-regulation of emerin, BAF, or LAP2alpha protein by
using short interfering RNA. Mouse embryo fibroblasts ablated for emerin protein
through gene knockout support the same level of HIV-1 infection as cells derived
from wild-type littermate control animals. As the expression of human emerin in
mouse knockout cells fails to affect the level of infectivity achieved in its
absence, we conclude that HIV-1 efficiently infects cells in the absence of
emerin protein and, by extension, that emerin is not a universally important
regulator of HIV-1 infectivity.
PMID- 17035313
TI - Cytoplasmic residues of herpes simplex virus glycoprotein gE required for
secondary envelopment and binding of tegument proteins VP22 and UL11 to gE and
gD.
AB - The final assembly of herpes simplex virus (HSV) involves binding of tegument
coated capsids to viral glycoprotein-enriched regions of the trans-Golgi network
(TGN) as enveloped virions bud into TGN membranes. We previously demonstrated
that HSV glycoproteins gE/gI and gD, acting in a redundant fashion, are essential
for this secondary envelopment. To define regions of the cytoplasmic (CT) domain
of gE required for secondary envelopment, HSVs lacking gD and expressing
truncated gE molecules were constructed. A central region (amino acids 470 to
495) of the gE CT domain was important for secondary envelopment, although more C
terminal residues also contributed. Tandem affinity purification (TAP) proteins
including fragments of the gE CT domain were used to identify tegument proteins
VP22 and UL11 as binding partners, and gE CT residues 470 to 495 were important
in this binding. VP22 and UL11 were precipitated from HSV-infected cells in
conjunction with full-length gE and gE molecules with more-C-terminal residues of
the CT domain. gD also bound VP22 and UL11. Expression of VP22 and gD or gE/gI in
cells by use of adenovirus (Ad) vectors provided evidence that other viral
proteins were not necessary for tegument/glycoprotein interactions. Substantial
quantities of VP22 and UL11 bound nonspecifically onto or were precipitated with
gE and gD molecules lacking all CT sequences, something that is very unlikely in
vivo. VP16 was precipitated equally whether gE/gI or gD was present in extracts
or not. These observations illustrated important properties of tegument proteins.
VP22, UL11, and VP16 are highly prone to binding nonspecifically to other
proteins, and this did not represent insolubility during our assays. Rather, it
likely reflects an inherent "stickiness" related to the formation of tegument.
Nevertheless, assays involving TAP proteins and viral proteins expressed by HSV
and Ad vectors supported the conclusion that VP22 and UL11 interact specifically
with the CT domains of gD and gE.
PMID- 17035314
TI - Evidence of influenza a virus RNA in siberian lake ice.
AB - Influenza A virus infects a large proportion of the human population annually,
sometimes leading to the deaths of millions. The biotic cycles of infection are
well characterized in the literature, including in studies of populations of
humans, poultry, swine, and migratory waterfowl. However, there are few studies
of abiotic reservoirs for this virus. Here, we report the preservation of
influenza A virus genes in ice and water from high-latitude lakes that are
visited by large numbers of migratory birds. The lakes are along the migratory
flight paths of birds flying into Asia, North America, Europe, and Africa. The
data suggest that influenza A virus, deposited as the birds begin their autumn
migration, can be preserved in lake ice. As birds return in the spring, the ice
melts, releasing the viruses. Therefore, temporal gene flow is facilitated
between the viruses shed during the previous year and the viruses newly acquired
by birds during winter months spent in the south. Above the Arctic Circle, the
cycles of entrapment in the ice and release by melting can be variable in length,
because some ice persists for several years, decades, or longer. This type of
temporal gene flow might be a feature common to viruses that can survive
entrapment in environmental ice and snow.
PMID- 17035315
TI - Inhibitory effect of gamma interferon on BK virus gene expression and
replication.
AB - BK virus (BKV) is widely accepted to be the causative agent of polyomavirus
nephropathy. In immunocompromised individuals, especially kidney transplant
recipients, BKV can replicate in kidney epithelial cells, causing loss of renal
function and eventual destruction of the graft. Advances in immunosuppressive
therapies may be partially responsible for the increasing incidence of
polyomavirus nephropathy among transplant recipients by more effectively
eliminating components of the immune system, such as gamma interferon (IFN-gamma)
producing lymphocytes, that keep BKV infections at a subclinical level. In this
study, we investigated the role of IFN-gamma in regulating lytic infection by
BKV. Treatment with IFN-gamma inhibited the expression of the viral early protein
large tumor antigen (TAg) and the late protein VP1 in a dose-dependent manner. We
detected 1.6- and 12-fold reductions in TAg transcripts at 48 and 96 h
postinfection, respectively, with 250 U/ml IFN-gamma, suggesting that IFN-gamma
mediated inhibition occurs at the level of transcription. Furthermore, IFN-gamma
inhibited the level of viral progeny production as much as 50-fold at a
multiplicity of infection (MOI) of 0.5 and 80-fold at an MOI of 0.1. The
inhibitory effects of IFN-gamma were similar for three different strains of BKV
examined. These results indicate an important role for IFN-gamma in regulating
BKV lytic infection.
PMID- 17035316
TI - Linker insertion mutations in the herpes simplex virus type 1 UL28 gene: effects
on UL28 interaction with UL15 and UL33 and identification of a second-site
mutation in the UL15 gene that suppresses a lethal UL28 mutation.
AB - The UL28 protein of herpes simplex virus type 1 (HSV-1) is one of seven viral
proteins required for the cleavage and packaging of viral DNA. Previous results
indicated that UL28 interacts with UL15 and UL33 to form a protein complex
(terminase) that is presumed to cleave concatemeric DNA into genome lengths. In
order to define the functional domains of UL28 that are important for DNA
cleavage/packaging, we constructed a series of HSV-1 mutants with linker
insertion and nonsense mutations in UL28. Insertions that blocked DNA cleavage
and packaging were found to be located in two regions of UL28: the first between
amino acids 200 to 400 and the second between amino acids 600 to 740. Insertions
located in the N terminus or in a region located between amino acids 400 and 600
did not affect virus replication. Insertions in the carboxyl terminus of the UL28
protein were found to interfere with the interaction of UL28 with UL33. In
contrast, all of the UL28 insertion mutants were found to interact with UL15 but
the interaction was reduced with mutants that failed to react with UL33.
Together, these observations were consistent with previous conclusions that UL15
and UL33 interact directly with UL28 but interact only indirectly with each
other. Revertant viruses that formed plaques on Vero cells were detected for one
of the lethal UL28 insertion mutants. DNA sequence analysis, in combination with
genetic complementation assays, demonstrated that a second-site mutation in the
UL15 gene restored the ability of the revertant to cleave and package viral DNA.
The isolation of an intergenic suppressor mutant provides direct genetic evidence
of an association between the UL28 and UL15 proteins and demonstrates that this
association is essential for DNA cleavage and packaging.
PMID- 17035317
TI - Antibody recognition and neutralization determinants on domains I and II of West
Nile Virus envelope protein.
AB - Previous studies have demonstrated that monoclonal antibodies (MAbs) against an
epitope on the lateral surface of domain III (DIII) of the West Nile virus (WNV)
envelope (E) strongly protect against infection in animals. Herein, we observed
significantly less efficient neutralization by 89 MAbs that recognized domain I
(DI) or II (DII) of WNV E protein. Moreover, in cells expressing Fc gamma
receptors, many of the DI- and DII-specific MAbs enhanced infection over a broad
range of concentrations. Using yeast surface display of E protein variants, we
identified 25 E protein residues to be critical for recognition by DI- or DII
specific neutralizing MAbs. These residues cluster into six novel and one
previously characterized epitope located on the lateral ridge of DI, the linker
region between DI and DIII, the hinge interface between DI and DII, and the
lateral ridge, central interface, dimer interface, and fusion loop of DII.
Approximately 45% of DI-DII-specific MAbs showed reduced binding with mutations
in the highly conserved fusion loop in DII: 85% of these (34 of 40) cross-reacted
with the distantly related dengue virus (DENV). In contrast, MAbs that bound the
other neutralizing epitopes in DI and DII showed no apparent cross-reactivity
with DENV E protein. Surprisingly, several of the neutralizing epitopes were
located in solvent-inaccessible positions in the context of the available
pseudoatomic model of WNV. Nonetheless, DI and DII MAbs protect against WNV
infection in mice, albeit with lower efficiency than DIII-specific neutralizing
MAbs.
PMID- 17035318
TI - Immunogenicity of heterologous recombinant adenovirus prime-boost vaccine
regimens is enhanced by circumventing vector cross-reactivity.
AB - The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in
human populations has led to the development of recombinant adenovirus (rAd)
vectors derived from rare Ad serotypes as vaccine candidates for human
immunodeficiency virus type 1 and other pathogens. Vaccine vectors have been
constructed from Ad subgroup B, including rAd11 and rAd35, as well as from Ad
subgroup D, including rAd49. However, the optimal combination of vectors for
heterologous rAd prime-boost vaccine regimens and the extent of cross-reactive
vector-specific neutralizing antibodies (NAbs) remain poorly defined. We have
shown previously that the closely related vectors rAd11 and rAd35 elicited low
levels of cross-reactive NAbs. Here we show that these cross-reactive NAbs
correlated with substantial sequence homology in the hexon hypervariable regions
(HVRs) and suppressed the immunogenicity of heterologous rAd prime-boost
regimens. In contrast, vectors with lower hexon HVR homology, such as rAd35 and
rAd49, did not elicit detectable cross-reactive vector-specific NAbs. Consistent
with these findings, rAd35-rAd49 vaccine regimens proved more immunogenic than
both rAd35-rAd5 and rAd35-rAd11 regimens in mice with anti-Ad5 immunity. These
data suggest that optimal heterologous rAd prime-boost regimens should include
two vectors that are both rare in human populations to circumvent preexisting
antivector immunity as well as sufficiently immunologically distinct to avoid
cross-reactive antivector immunity.
PMID- 17035320
TI - Simian immunodeficiency virus SIVmac239 infection of major histocompatibility
complex-identical cynomolgus macaques from Mauritius.
AB - Nonhuman primates are widely used to study correlates of protective immunity in
AIDS research. Successful cellular immune responses have been difficult to
identify because heterogeneity within macaque major histocompatibility complex
(MHC) genes results in quantitative and qualitative differences in immune
responses. Here we use microsatellite analysis to show that simian
immunodeficiency virus (SIV)-susceptible cynomolgus macaques (Macaca
fascicularis) from the Indian Ocean island of Mauritius have extremely simple MHC
genetics, with six common haplotypes accounting for two-thirds of the MHC
haplotypes in feral animals. Remarkably, 39% of Mauritian cynomolgus macaques
carry at least one complete copy of the most frequent MHC haplotype, and 8% of
these animals are homozygous. In stark contrast, entire MHC haplotypes are rarely
conserved in unrelated Indian rhesus macaques. After intrarectal infection with
highly pathogenic SIVmac239 virus, a pair of MHC-identical Mauritian cynomolgus
macaques mounted concordant cellular immune responses comparable to those
previously reported for a pair of monozygotic twins infected with the same strain
of human immunodeficiency virus. Our identification of relatively abundant SIV
susceptible, MHC-identical macaques will facilitate research into protective
cellular immunity.
PMID- 17035319
TI - Epstein-barr virus latent membrane protein 2B (LMP2B) modulates LMP2A activity.
AB - Latent membrane protein 2A (LMP2A) and LMP2B are viral proteins expressed during
Epstein-Barr virus (EBV) latency in EBV-infected B cells both in cell culture and
in vivo. LMP2A has important roles in modulating B-cell receptor (BCR) signal
transduction by associating with the cellular tyrosine kinases Lyn and Syk via
specific phosphotyrosine motifs found within the LMP2A N-terminal tail domain.
LMP2A has been shown to alter normal BCR signal transduction in B cells by
reducing levels of Lyn and by blocking tyrosine phosphorylation and calcium
mobilization following BCR cross-linking. Although little is currently known
about the function of LMP2B in B cells, the similarity in structure between LMP2A
and LMP2B suggests that they may localize to the same cellular compartments. To
investigate the function of LMP2B, B-cell lines expressing LMP2A, LMP2B,
LMP2A/LMP2B, and the relevant vector controls were analyzed. As was previously
shown, cells expressing LMP2A had a dramatic block in normal BCR signal
transduction as measured by calcium mobilization and tyrosine phosphorylation.
There was no effect on BCR signal transduction in cells expressing LMP2B.
Interestingly, when LMP2B was expressed in conjunction with LMP2A, there was a
restoration of normal BCR signal transduction upon BCR cross-linking. The
expression of LMP2B did not alter the cellular localization of LMP2A but did bind
to and prevent the phosphorylation of LMP2A. A restoration of Lyn levels, but not
a change in LMP2A levels, was also observed in cells coexpressing LMP2B with
LMP2A. From these results, we conclude that LMP2B modulates LMP2A activity.
PMID- 17035321
TI - The African swine fever virus nonstructural protein pB602L is required for
formation of the icosahedral capsid of the virus particle.
AB - African swine fever virus (ASFV) protein pB602L has been described as a molecular
chaperone for the correct folding of the major capsid protein p72. We have
studied the function of protein pB602L during the viral assembly process by using
a recombinant ASFV, vB602Li, which inducibly expresses the gene coding for this
protein. We show that protein pB602L is a late nonstructural protein, which, in
contrast with protein p72, is excluded from the viral factory. Repression of
protein pB602L synthesis inhibits the proteolytic processing of the two viral
polyproteins pp220 and pp62 and leads to a decrease in the levels of protein p72
and a delocalization of the capsid protein pE120R. As shown by electron
microscopy analysis of cells infected with the recombinant virus vB602Li, the
viral assembly process is severely altered in the absence of protein pB602L, with
the generation of aberrant "zipper-like" structures instead of icosahedral virus
particles. These "zipper-like" structures are similar to those found in cells
infected under restrictive conditions with the recombinant virus vA72 inducibly
expressing protein p72. Immunoelectron microscopy studies show that the abnormal
forms generated in the absence of protein pB602L contain the inner envelope
protein p17 and the two polyproteins but lack the capsid proteins p72 and pE120R.
These findings indicate that protein pB602L is essential for the assembly of the
icosahedral capsid of the virus particle.
PMID- 17035322
TI - Functional characterization of Kaposi's sarcoma-associated herpesvirus ORF45 by
bacterial artificial chromosome-based mutagenesis.
AB - Open reading frame 45 (ORF45) of Kaposi's sarcoma-associated herpesvirus (KSHV)
encodes an immediate-early protein. This protein is also present in virions as a
tegument protein. ORF45 protein interacts with interferon regulatory factor 7
(IRF-7) and inhibits virus-induced type I interferon production by blocking
activation of IRF-7. To define further the function of ORF45 and the mechanism
underlying its action, we constructed an ORF45-null recombinant virus genome (BAC
stop45) by using a bacterial artificial chromosome (BAC) system. Stable 293T
cells carrying the BAC36 (wild type) and BAC-stop45 genomes were generated. When
monolayers of 293T BAC36 and 293T BAC-stop45 cells were induced with 12-O
tetradecanoylphorbol-13-acetate and sodium butyrate, no significant difference
was found between them in overall viral gene expression and lytic DNA
replication, but induced 293T BAC-stop45 cells released 10-fold fewer virions to
the medium than did 293T BAC36 cells. When ORF45-null virus was used to infect
cells, lower infectivity was observed than for wild-type BAC36. These results
suggest that KSHV ORF45 plays roles in both early and late stages of viral
infection, probably in viral ingress and egress.
PMID- 17035323
TI - CD4+ T-cell responses are required for clearance of West Nile virus from the
central nervous system.
AB - Although studies have established that innate and adaptive immune responses are
important in controlling West Nile virus (WNV) infection, the function of CD4(+)
T lymphocytes in modulating viral pathogenesis is less well characterized. Using
a mouse model, we examined the role of CD4(+) T cells in coordinating protection
against WNV infection. A genetic or acquired deficiency of CD4(+) T cells
resulted in a protracted WNV infection in the central nervous system (CNS) that
culminated in uniform lethality by 50 days after infection. Mice surviving past
day 10 had high-level persistent WNV infection in the CNS compared to wild-type
mice, even 45 days following infection. The absence of CD4(+) T-cell help did not
affect the kinetics of WNV infection in the spleen and serum, suggesting a role
for CD4-independent clearance mechanisms in peripheral tissues. WNV-specific
immunoglobulin M (IgM) levels were similar to those of wild-type mice in CD4
deficient mice early during infection but dropped approximately 20-fold at day 15
postinfection, whereas IgG levels in CD4-deficient mice were approximately 100-
to 1,000-fold lower than in wild-type mice throughout the course of infection.
WNV-specific CD8(+) T-cell activation and trafficking to the CNS were unaffected
by the absence of CD4(+) T cells at day 9 postinfection but were markedly
compromised at day 15. Our experiments suggest that the dominant protective role
of CD4(+) T cells during primary WNV infection is to provide help for antibody
responses and sustain WNV-specific CD8(+) T-cell responses in the CNS that enable
viral clearance.
PMID- 17035324
TI - Human immunodeficiency virus type 1 resistance to the small molecule maturation
inhibitor 3-O-(3',3'-dimethylsuccinyl)-betulinic acid is conferred by a variety
of single amino acid substitutions at the CA-SP1 cleavage site in Gag.
AB - The compound 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB) potently and
specifically inhibits human immunodeficiency virus type 1 (HIV-1) replication by
delaying the cleavage of the CA-SP1 junction in Gag, leading to impaired
maturation of the viral core. In this study, we investigated HIV-1 resistance to
DSB by analyzing HIV-1 mutants encoding a variety of individual amino acid
substitutions in the CA-SP1 cleavage site. Three of the substitutions were lethal
to HIV-1 replication owing to a deleterious effect on particle assembly. The
remaining mutants exhibited a range of replication efficiencies; however, each
mutant was capable of replicating in the presence of concentrations of DSB that
effectively inhibited wild-type HIV-1. Mutations conferring resistance to DSB
also led to impaired binding of the compound to immature HIV-1 virions and loss
of DSB-mediated inhibition of cleavage of Gag. Surprisingly, two of the DSB
resistant mutants retained an intermediate ability to bind the compound,
suggesting that binding of DSB to immature HIV-1 particles may not be sufficient
for antiviral activity. Overall, our results indicate that Gag amino acids L363
and A364 are critical for inhibition of HIV-1 replication by DSB and suggest that
these residues form key contacts with the drug in the context of the assembling
HIV-1 particle. These results have implications for the design of and screening
for novel inhibitors of HIV-1 maturation.
PMID- 17035325
TI - Stoichiometry of murine leukemia virus envelope protein-mediated fusion and its
neutralization.
AB - Envelope glycoproteins (Envs) of retroviruses form trimers that mediate fusion
between viral and cellular membranes and are the targets for neutralizing
antibodies. Understanding in detail how Env trimers mediate membrane fusion, and
how antibodies interfere with this process, is a fundamental problem in biology
with practical implications for the development of antiviral drugs and vaccines.
We investigated the stoichiometry of Env-mediated fusion and its inhibition by
antibody by inserting an epitope from human immunodeficiency virus for a
neutralizing antibody (2F5) into the surface (SU) or transmembrane (TM) protein
of murine leukemia virus Env, along with point mutations that abrogate SU and TM
function but complement one another. We transfected various combinations of these
Env genes and investigated Env-mediated cell fusion and its inhibition by 2F5
antibody. Our results showed that heterotrimers with one functional SU molecule
were fusion competent in complementation experiments and that one antibody
molecule was sufficient to inactivate the fusion function of a trimer when its
epitope was in functional SU or TM. 2F5 antibody could also neutralize trimers
with the 2F5 epitope in nonfunctional SU or TM, but less efficiently.
PMID- 17035326
TI - Increased frequency of circulating CCR5+ CD4+ T cells in human immunodeficiency
virus type 2 infection.
AB - CCR5 expression determines susceptibility to infection, cell tropism, and the
rate of human immunodeficiency virus type 1 (HIV-1) disease progression. CCR5 is
also considered the major HIV-2 coreceptor in vivo, in spite of broad coreceptor
use in vitro. Here we report a significantly increased proportion of memory
effector CD4 T cells expressing CCR5 in HIV-2-infected patients correlating with
CD4 depletion. Moreover, HIV-2 proviral DNA was essentially restricted to memory
effector CD4, suggesting that this is the main target for HIV-2. Similar levels
of proviral DNA were found in the two infection categories. Thus, the reduced
viremia and slow rate of CD4 decline that characterize HIV-2 infection seem to be
unrelated to coreceptor availability.
PMID- 17035327
TI - Contribution of T-cell receptor repertoire breadth to the dominance of epitope
specific CD8+ T-lymphocyte responses.
AB - Dominant epitope-specific CD8(+) T-lymphocyte responses play a central role in
controlling viral spread. We explored the basis for the development of this
focused immune response in simian immunodeficiency virus (SIV)- and simian-human
immunodeficiency virus (SHIV)-infected rhesus monkeys through the use of two
dominant (p11C and p199RY) and two subdominant (p68A and p56A) epitopes. Using
real-time PCR to quantitate T-cell receptor (TCR) variable region beta (Vbeta)
family usage, we show that CD8(+) T-lymphocyte populations specific for dominant
epitopes are characterized by a diverse Vbeta repertoire, whereas those specific
for subdominant epitopes employ a dramatically more focused Vbeta repertoire. We
also demonstrate that dominant epitope-specific CD8(+) T lymphocytes employ TCRs
with multiple CDR3 lengths, whereas subdominant epitope-specific cells employ
TCRs with a more restricted CDR3 length. Thus, the relative dominance of an
epitope-specific CD8(+) T-lymphocyte response reflects the clonal diversity of
that response. These findings suggest that the limited clonal repertoire of
subdominant epitope-specific CD8(+) T-lymphocyte populations may limit the
ability of these epitope-specific T-lymphocyte populations to expand and
therefore limit the ability of these cell populations to contribute to the
control of viral replication.
PMID- 17035328
TI - Prolonged adherence of human immunodeficiency virus-derived vector particles to
hematopoietic target cells leads to secondary transduction in vitro and in vivo.
AB - Human immunodeficiency virus type 1-derived lentivirus vectors bearing the
vesicular stomatitis virus G (VSV-G) envelope glycoprotein demonstrate a wide
host range and can stably transduce quiescent hematopoietic stem cells. In light
of concerns about biosafety and potential germ line transmission, they have been
used predominantly for ex vivo strategies, thought to ensure the removal of
excess surface-bound particles and prevent in vivo dissemination. Studies
presented here instead reveal prolonged particle adherence after ex vivo
exposure, despite serial wash procedures, with subsequent transduction of
secondary target cells in direct and transwell cocultures. We explored the
critical parameters affecting particle retention and transfer and show that
attachment to the cell surface selectively protects virus particles from serum
complement-mediated inactivation. Moreover, studies with nonmyeloablated murine
recipients show that transplantation of vector-exposed, washed hematopoietic
cells results in systemic dissemination of functional VSV-G/lentivector
particles. We demonstrate genetic marking by inadvertent transfer of vector
particles and prolonged expression of transgene product in recipient tissues. Our
findings have implications for biosafety, vector design, and cell biology
research.
PMID- 17035329
TI - Characterization of an immunodominant antigenic site on GB virus C glycoprotein
E2 that is involved in cell binding.
AB - GB virus type C (GBV-C) is a human flavivirus that may cause persistent
infection, although most infected individuals clear viremia and develop
antibodies to the envelope glycoprotein E2. To study GBV-C E2 antigenicity and
cell binding, murine anti-E2 monoclonal antibodies (MAbs) were evaluated to
topologically map immunogenic sites on GBV-C E2 and for the ability to detect or
block recombinant E2 binding to various cell lines. Five competition groups of
MAbs were identified. Groups I and II did not compete with each other. Group III
competed with both groups I and II. Group IV did not compete with group I, II, or
III. One MAb competed with all of the other MAbs, suggesting that the epitopes
bound by these MAbs are intimately related. Individually, none of the MAbs
competed extensively with polyclonal human convalescent antibody (PcAb); however,
combinations of all five MAb groups completely blocked PcAb binding to E2,
suggesting that the epitopes bound by these MAbs form a single, immunodominant
antigenic site. Only group I and III MAbs detected purified recombinant E2 bound
to cells in binding assays. In contrast, group II MAbs neutralized the binding of
E2 to cells. Both PcAb and MAbs were conformation dependent, with the exception
of one group II MAb (M6). M6 bound to a five-amino-acid sequence on E2 if the
peptide included four C-terminal or eight N-terminal residues, suggesting that
the GBV-C E2 protein contains a single immunodominant antigenic site which
includes a complex epitope that is involved in specific cellular binding.
PMID- 17035330
TI - Walleye dermal sarcoma virus retroviral cyclin directly contacts TAF9.
AB - Walleye dermal sarcoma virus (WDSV) is a complex retrovirus associated with
dermal sarcomas in walleye fish. A WDSV accessory gene encodes a cyclin homolog
or retroviral cyclin (rv-cyclin). WDSV rv-cyclin was found to be associated with
transcription complexes and to affect transcription in a cell-type and promoter
dependent manner. It inhibited the WDSV promoter in walleye fibroblasts and
activated transcription from GAL4 promoters when fused to the GAL4 DNA binding
domain, and an activation domain (AD) has been localized to 30 amino acids in the
carboxyl region. rv-cyclin can block the pulldown of transcription coactivators
by the AD of VP16, and the isolated rv-cyclin AD interferes specifically with the
interaction between the carboxyl halves of the VP16 AD, VP16C, and TATA-binding
protein-associated factor 9 (TAF9). The carboxyl region and isolated AD can bind
TAF9 directly in assays of protein-protein interaction in vitro. Furthermore, rv
cyclin and the isolated rv-cyclin AD interfere specifically with the function of
VP16C in transcription assays. A previously identified motif within the VP16C
sequence mediates TAF9 binding, and this motif is present in the activation
domains of a variety of TAF9-binding transcriptional activators. A similar motif
is present in the rv-cyclin AD, and point mutations within this motif affect rv
cyclin function and protein-protein interactions. The results support a model of
transcription regulation by direct interaction with TAF9.
PMID- 17035331
TI - Construction and mutagenesis of an artificial bicistronic tick-borne encephalitis
virus genome reveals an essential function of the second transmembrane region of
protein e in flavivirus assembly.
AB - Flaviviruses have a monopartite positive-stranded RNA genome, which serves as the
sole mRNA for protein translation. Cap-dependent translation produces a
polyprotein precursor that is co- and posttranslationally processed by proteases
to yield the final protein products. In this study, using tick-borne encephalitis
virus (TBEV), we constructed an artificial bicistronic flavivirus genome (TBEV
bc) in which the capsid protein and the nonstructural proteins were still encoded
in the cap cistron but the coding region for the surface proteins prM and E was
moved to a separate translation unit under the control of an internal ribosome
entry site element inserted into the 3' noncoding region. Mutant TBEV-bc was
shown to produce particles that packaged the bicistronic RNA genome and were
infectious for BHK-21 cells and mice. Compared to wild-type controls, however,
TBEV-bc was less efficient in both RNA replication and infectious particle
formation. We took advantage of the separate expression of the E protein in this
system to investigate the role in viral assembly of the second transmembrane
region of protein E (E-TM2), a second copy of which was retained in the cap
cistron to fulfill its other role as an internal signal sequence in the
polyprotein. Deletion analysis and replacement of the entire TBEV E-TM2 region
with its counterpart from another flavivirus revealed that this element, apart
from its role as a signal sequence, is important for virion formation.
PMID- 17035332
TI - NFAT4 is required for JC virus infection of glial cells.
AB - The human polyomavirus JC virus (JCV) infects 70% of the population worldwide. In
immunosuppressed patients, JCV infection can lead to progressive multifocal
leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous
system (CNS). The majority of PML cases occur in the setting of human
immunodeficiency virus (HIV) infection, and it has been suggested that the link
between HIV and the development of PML is in part related to the production of
numerous cytokines in the CNS during HIV infection. To examine the link between
the expression of inflammatory cytokines and JCV infection, we tested an anti
inflammatory compound, cyclosporine A (CsA), for its ability to block JCV
infection of glial cells. We found that CsA inhibited JCV infection by preventing
the activation of the transcription factor nuclear factor of activated T cells 4
(NFAT4). Luciferase reporter assays and chromatin immunoprecipitation assays
revealed that NFAT4 directly bound the JCV promoter during infection and was
important for the activation of both early and late transcription. In addition,
the expression of the JCV early viral gene products increased NFAT activity to
further aid viral transcription. The necessity of NFAT for JCV infection suggests
that calcium signaling and the activation of NFAT in glial cells are required for
JCV infection of the CNS.
PMID- 17035333
TI - Rotavirus nonstructural glycoprotein NSP4 is secreted from the apical surfaces of
polarized epithelial cells.
AB - NSP4, a nonstructural glycoprotein encoded by rotavirus, is involved in the
morphogenesis of virus particles in the endoplasmic reticulum of infected cells.
NSP4 is also implicated in the pathophysiology of rotavirus-induced diarrhea by
acting as an enterotoxin. To mediate enterotoxic effects in vivo, NSP4 must be
secreted or released from rotavirus-infected cells in a soluble form; however,
previous studies have indicated that NSP4 is a transmembrane glycoprotein
localized within endomembrane compartments in infected cells. In this study, we
examined the fate of NSP4 synthesized in Caco-2 cells infected with bovine
rotavirus. Our studies reveal that NSP4 is actively secreted into the culture
medium, preferentially from the infected-cell apical surface. The secretion of
NSP4 is dramatically inhibited by brefeldin A and monensin, suggesting that a
Golgi-dependent pathway is involved in release of the protein. In agreement with
the proposed involvement of the Golgi apparatus during secretion, secreted NSP4
appears to undergo additional posttranslational modification compared to its cell
associated counterpart and is partially resistant to deglycosylation by
endoglycosidase H. Our experiments identify a novel, soluble form of NSP4
secreted from virus-infected cells with the potential to carry out the
enterotoxigenic role previously attributed to recombinant forms of the protein.
PMID- 17035334
TI - Spleen-dependent turnover of CD11b peripheral blood B lymphocytes in bovine
leukemia virus-infected sheep.
AB - Lymphocyte homeostasis is determined by a critical balance between cell
proliferation and death, an equilibrium which is deregulated in bovine leukemia
virus (BLV)-infected sheep. We have previously shown that an excess of
proliferation occurs in lymphoid tissues and that the peripheral blood population
is prone to increased cell death. To further understand the mechanisms involved,
we evaluated the physiological role of the spleen in this accelerated turnover.
To this end, B lymphocytes were labeled in vivo using a fluorescent marker
(carboxyfluorescein diacetate succinimidyl ester), and the cell kinetic
parameters (proliferation and death rates) of animals before and after
splenectomy were compared. We show that the enhanced cell death observed in BLV
infected sheep is abrogated after splenectomy, revealing a key role of the spleen
in B-lymphocyte dynamics.
PMID- 17035336
TI - Treatment of ischaemic left ventricular dysfunction with milrinone or dobutamine
administered during coronary artery stenosis in the presence of beta blockade in
pigs.
AB - BACKGROUND: This study examines the effects of phosphodiesterase type III
(PDEIII) inhibition vs beta stimulation on global function of the left ventricle
(LV) and systemic haemodynamics in a porcine model of acute coronary stenosis
with beta blockade. METHODS: A total of 18 adult swine were anaesthetized.
Micromanometer-tipped catheters were placed in the ascending aorta and LV. Two
pairs of ultrasonic dimension transducers were placed in the subendocardium on
the short axis proximal to a left anterior descending (LAD) artery occluder and
the long axis of the LV. Before ischaemia, i.v. esmolol was infused to decrease
baseline heart rate (HR) by approximately 25%, and all animals received an
esmolol infusion (150 microg kg(-1) min(-1)). Ischaemia was produced by reducing
the flow in the LAD artery by approximately 80%, from 17(4) to 3(2) ml min(-1).
Animals were randomized to receive (after esmolol) one of the following: no drug,
sham only (Group 1, n=6), control (C); 50 microg kg(-1) i.v. milrinone (Group 2,
n=6) followed by 0.375 microg kg(-1) min(-1) (M); or incremental doses of
dobutamine (Group 3, n=6) every 10 min (5, 10 and 20 microg kg(-1) min(-1)) (D).
Left ventricular function data obtained included HR, arterial and LV pressures,
cardiac output (CO), Emax and dP/dT. Measurements were taken during five time
periods: before ischaemia (at baseline, after esmolol) and every 10 min during
ischaemia (at 10, 20 and 30 min). RESULTS: The effects of beta blockade and
ischaemia had a significant impact on contractility (Emax) in Group M and
myocardial performance (left ventricular end-diastolic pressure, LVEDP) in all
groups. Left ventricular function (Emax, CO, LVEDP and SVR) was better preserved
when milrinone was added in Group M. A moderate dose of dobutamine (10 microg kg(
1) min(-1)) increased CO. Only the high dose (20 microg kg(-1) min(-1)) improved
contractility (Emax), but at the expense of increased SVR. Also, LVEDP with
either dose of dobutamine remained high and unchanged. CONCLUSIONS: From our
limited findings, it would appear that there may, theoretically, be some benefit
for using milrinone in preference to other inotropic drugs in the presence of
beta blockade. Milrinone administration should be considered in patients with
acute ischaemic LV dysfunction and preexisting beta blockade before using other
inotropic drugs such as beta stimulants.
PMID- 17035335
TI - The betaretrovirus Mason-Pfizer monkey virus selectively excludes simian APOBEC3G
from virion particles.
AB - The APOBEC3 protein family can constitute a potent barrier to the successful
infection of mammalian species by retroviruses. Therefore, any retrovirus that
has evolved the ability to replicate in a given animal must have developed
mechanisms that allow it to avoid or inhibit the APOBEC3 proteins expressed in
that animal. Here, we demonstrate that Mason-Pfizer monkey virus (MPMV) is
resistant to inhibition by the APOBEC3G protein expressed in its normal host, the
rhesus macaque, but highly susceptible to inhibition by murine APOBEC3 (mA3).
MPMV virion particles fail to package rhesus APOBEC3G (rA3G), and MPMV Gag binds
rA3G poorly in coexpressing cells. In contrast, MPMV virions package mA3
efficiently and MPMV Gag-mA3 complexes are readily detected. Moreover, mA3, but
not rA3G, partially colocalizes with MPMV Gag in the cytoplasm of coexpressing
cells. Previously, we have demonstrated that murine leukemia virus also escapes
inhibition by APOBEC3 proteins by avoiding virion incorporation of its cognate
APOBEC3 protein, mA3, yet is inhibited by primate APOBEC3G proteins, which it
packages effectively (B. P. Doehle, A. Schafer, H. L. Wiegand, H. P. Bogerd, and
B. R. Cullen, J. Virol. 79:8201-8207, 2005). The finding that two essentially
unrelated beta- and gammaretroviruses use similar mechanisms to escape inhibition
by the APOBEC3 proteins found in their normal host species suggests that the
selective exclusion of APOBEC3 proteins from virion particles may be a general
mechanism used by simple mammalian retroviruses.
PMID- 17035337
TI - Spinal fusion surgery in children with non-idiopathic scoliosis: is there a need
for routine postoperative ventilation?
AB - BACKGROUND: The perioperative management of children with non-idiopathic
scoliosis undergoing spinal deformity surgery has not been standardized and the
current practice is to routinely ventilate these patients in the postoperative
period. This study reports the experience from a single institution and evaluates
the need and reasons for postoperative ventilation. Details of ventilated
patients are presented. METHODS: All patients undergoing spinal fusion surgery
for non-idiopathic scoliosis were recorded prospectively (2003-4). Patients were
anaesthetized according to a standardized technique. Physical characteristics,
cardiopulmonary function, intraoperative blood loss and fluid requirement,
postoperative need for ventilation and all perioperative adverse events were
recorded on a computer database. RESULTS: A total of 76.2% of patients were
safely extubated at the end of surgery without any further complications or need
for re-ventilation; 23.8% of patients required postoperative ventilation with
half of the cases being planned before operation and 40% of all patients with
Duchenne muscular dystrophy (DMD) required postoperative ventilation. There were
no specific factors that could predict the need for postoperative ventilation,
although an increased tendency for children with DMD and those with a
preoperative forced vital capacity <30% towards requiring postoperative
ventilation was observed. CONCLUSIONS: Early extubation can be safely performed
after spinal deformity surgery for non-idiopathic scoliosis. The use of short
acting anaesthetics, drugs to reduce blood loss, experienced spinal anaesthetists
and the availability of intensive care support are all essential for a good
outcome in patients with neuromuscular disease and cardiopulmonary co-morbidity.
PMID- 17035338
TI - Requirement of tumor necrosis factor alpha and nuclear factor-kappaB in the
induction by IFN-gamma of inducible nitric oxide synthase in macrophages.
AB - IFN-gamma induces NO production, inducible NO synthase (iNOS) protein, and
promoter expression in mouse macrophage cells. Mutation of IFN regulatory factor
1 responsive element, gamma-activated site, as well as NF-kappaB elements in the
murine iNOS promoter strongly reduced IFN-gamma-induced iNOS transcriptional
activity. The role of NF-kappaB activation in iNOS induction by IFN-gamma was
corroborated by overexpression of the NF-kappaB inhibitory protein IkappaBalpha,
which inhibited iNOS promoter activity induced by IFN-gamma. In addition, IFN
gamma treatment induced p65 binding to the iNOS promoter by chromatin
immunoprecipitation assay and NF-kappaB binding to DNA by EMSA, although with a
delayed kinetics, suggesting an indirect autocrine role for another cytokine
produced in response to IFN-gamma. It is interesting that we found that IFN-gamma
induced TNF-alpha secretion, and the induction of iNOS expression by IFN-gamma
was abolished in primary peritoneal macrophages from TNF-alpha-deficient (TNF
alpha-/-) mice or in RAW 264.7 cells treated with anti-TNF-alpha neutralizing
antibodies. Moreover, exogenous addition of recombinant mouse TNF-alpha restored
iNOS expression induced by IFN-gamma in TNF-alpha-/- mice. It is intriguing that
NF-kappaB binding to DNA in response to IFN-gamma treatment was absent in TNF
alpha-/- mice. Taken together, our data suggest that the TNF-alpha produced in
response to IFN-gamma is required for iNOS induction by activating NF-kappaB
transcription factor.
PMID- 17035339
TI - VDR-dependent regulation of mast cell maturation mediated by 1,25
dihydroxyvitamin D3.
AB - 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is a secosteroid hormone that regulates
bone metabolism, controls calcium homeostasis, and possesses immunomodulatory
properties. We show here that 1,25(OH)2D3 contributes to the regulation of
development and function of mast cells, which play a critical role in several
inflammatory disorders. 1,25(OH)2D3 promotes apoptosis and inhibits maturation of
mouse bone marrow-derived mast cell precursors. Dose-dependent inhibition of mast
cell differentiation by 1,25(OH)2D3 is observed at discrete, intermediate stages
of mast cell development, identified by expression of c-kit, FcepsilonRI, and IL
3 receptor-alpha chain, and depends on the expression of the vitamin D receptor
(VDR). It is important that mast cell progenitors obtained from VDR-ablated mice
undergo an accelerated maturation in vitro and give rise to more responsive mast
cells than wild-type. Furthermore, histological analysis of mast cell density in
peripheral tissues reveals a moderate increase in the number of mast cells in the
skin of VDR-deficient mice compared with wild-type animals. These data support
the hypothesis of a physiological role of 1,25(OH)2D3 in mast cell development
and suggest novel, therapeutic uses of 1,25(OH)2D3 analogs.
PMID- 17035340
TI - The secretion of HMGB1 is required for the migration of maturing dendritic cells.
AB - Chemokines regulate the migration and the maturation of dendritic cells (DC)
licensed by microbial constituents. We have recently found that the function of
DC, including their ability to activate naive, allogeneic CD4+ T cells, requires
the autocrine/paracrine release of the nuclear protein high mobility group box 1
(HMGB1). We show here that human myeloid DC, which rapidly secrete upon
maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up
regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to
migrate in response to chemokine receptor ligands. The events are apparently
causally related: DC challenged with LPS in the presence of HMGB1-specific
antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and
to rearrange actin-rich structures. Moreover, DC matured in the presence of anti
HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the
CXCR4 ligand CXCL12. The blockade of receptor for advanced glycation end products
(RAGE), the best-characterized membrane receptor for HMGB1, impinges as well on
the up-regulation of chemokine receptors and on responsiveness to CCL19 and
CXCL12. Our data suggest that the autocrine/paracrine release of HMGB1 and the
integrity of the HMGB1/RAGE pathway are required for the migratory function of
DC.
PMID- 17035341
TI - How common are electronic health records in the United States? A summary of the
evidence.
AB - Electronic health records (EHRs) are promising tools to improve quality and
efficiency in health care, but data on their adoption rate are limited. We
identified surveys on EHR adoption and assessed their quality. Although surveys
returned widely different estimates of EHR use, when available information is
limited to studies of high or medium quality, national estimates are possible:
Through 2005, approximately 23.9 percent of physicians used EHRs in the
ambulatory setting, while 5 percent of hospitals used computerized physician
order entry. Large gaps in knowledge, including information about EHR use among
safety-net providers, pose critical challenges for the development of policies
aimed at speeding adoption.
PMID- 17035342
TI - Activity of tigecycline against ESBL-producing and AmpC-hyperproducing
Enterobacteriaceae from south-east England.
PMID- 17035343
TI - Maternal illness and drug/medication use during the period surrounding pregnancy
and risk of childhood leukemia among offspring.
AB - Maternal illness and drug/medication use (prescription, over-the-counter, and
illicit) during pregnancy might be related to childhood leukemia risk. These
issues were evaluated using data (1995-2002) from the Northern California
Childhood Leukemia Study. The authors selected 365 children under age 15 years
who had been diagnosed with incident leukemia and birth certificate controls who
were matched to them on age, sex, Hispanic ethnicity, and maternal race. Data on
maternal illnesses and drug use from before pregnancy through breastfeeding were
obtained by interview with the biologic mother and were analyzed by conditional
logistic regression. Maternal history of influenza/pneumonia was associated with
a statistically significant increased risk of acute lymphoblastic leukemia (ALL)
in the offspring (odds ratio (OR) = 1.89, 95% confidence interval (CI): 1.24,
2.89), although the risk was nonsignificant for common ALL (OR = 1.41, 95% CI:
0.75, 2.63). A similar pattern of increased risk was found for history of
sexually transmitted disease. Use of iron supplements was indicative of decreased
ALL risk (OR = 0.67, 95% CI: 0.47, 0.94). Observing an increased risk of leukemia
in children of mothers reporting a history of influenza/pneumonia and sexually
transmitted disease around the time of pregnancy suggests that maternal infection
might contribute to the etiology of leukemia. Furthermore, maternal iron
supplement use may be protective against childhood leukemia.
PMID- 17035344
TI - Cystatin C and measures of physical function in elderly adults: the Health,
Aging, and Body Composition (HABC) Study.
AB - Most studies of the relation between kidney function and physical function have
been conducted in persons with advanced kidney disease and have used creatinine
based measures of kidney function. Cystatin C concentration is a measure of
kidney function that is independent of muscle mass, unlike creatinine. Using
baseline data on 3,043 elderly adults from the Health, Aging, and Body
Composition Study (Blacks and Whites recruited from Pittsburgh, Pennsylvania, and
Memphis, Tennessee, in 1997-1998), the authors examined the cross-sectional
association between cystatin C level and performance on several tests of physical
function. After adjustment for demographic and lifestyle variables, chronic
health conditions, and inflammation, each standard-deviation (0.34 mg/liter)
increase in cystatin C concentration was associated with 1.32 odds (95%
confidence interval (CI): 1.20, 1.46) of not completing a 400-m walk, a 10.9
second (95% CI: 8.1, 13.8) slower 400-m walk time, a 0.11-point (95% CI: 0.09,
0.13) reduction in lower extremity performance score, a 1.12-kg (95% CI: 0.83,
1.40) lower grip strength, and a 4.7-nm (95% CI: 3.5, 5.9) lower knee extension
strength. In contrast, when kidney function was measured by estimated glomerular
filtration rate, the association of kidney function with physical function was
only evident below 60 ml/minute/1.73 m2. In these older adults, mild decrements
in kidney function, as measured by cystatin C concentration, were associated with
poorer physical function.
PMID- 17035345
TI - Genetic background influences Th cell differentiation by controlling the capacity
for IL-2-induced IL-4 production by naive CD4+ T cells.
AB - Comparative studies using T(h)2-prone BALB/c and T(h)1-prone C57BL/6 mice were
performed to clarify the influence of genetic background on T(h) cell
differentiation. The results showed IL-4, the production of which is induced by
IL-2, to be much more abundantly produced by BALB/c naive CD4(+) T cells than by
C57BL/6 naive CD4(+) T cells, thereby leading to a tendency for differentiation
toward T(h)2 in BALB/c naive CD4(+) T cells. This difference in IL-4 production
between the two naive CD4(+) T cells appeared to be attributable to specific
intracellular signaling events. Signal transducer and activator of transcription
5 (STAT5) was preferentially activated by IL-2 in CD4(+) T cells developing in
BALB/c in contrast to the corresponding cells in C57BL/6. In addition, IL-4 also
induced stronger STAT5 activation in CD4(+) T cells developing in BALB/c than in
those developing in C57BL/6, whereas STAT6 was equally activated in these two
cells. Further results supported the involvement of STAT5 in the difference in
T(h) cell differentiation between BALB/c and C57BL/6 naive CD4(+) T cells.
STAT5A(-)(/)(-) naive CD4(+) T cells with the BALB/c genetic background showed
markedly less IL-2-induced IL-4 production than BALB/c naive CD4(+) T cells.
Conversely, forced expression of the constitutively active forms of STAT5A and
STAT5B in C57BL/6 naive CD4(+) T cells promoted the differentiation of T(h)2
cells. Thus, our results indicate IL-2-induced IL-4 production by naive CD4(+) T
cells, in which STAT5 activation is involved and directly controlled by the
genetic background, to influence T(h) cell differentiation in murine strains.
PMID- 17035346
TI - Efficiency of peptide presentation by dendritic cells compared with other cell
types: implications for cross-priming.
AB - Dendritic cells (DCs) play a key role in the induction of cellular immune
responses by harvesting antigens from peripheral tissue for cross-priming CD8(+)
T cells. It has been demonstrated that apoptotic bodies, whole- or degraded-cell
associated or soluble antigens as well as heat shock protein-bound peptides can
be taken up, processed and cross-presented by DCs. Since cells are continuously
releasing peptides from their surface MHC molecules, DCs in the tissues are
exposed to such peptides and might process and present them to T cells as an
additional pathway for cross-priming. To investigate this possibility, we
compared and characterized the presentation of exogenous peptides by DCs and
other cell types employing novel recombinant antibodies with TCR-like
specificities for specific peptide-MHC complexes (pMHCs). These analyses reveal
that loading of immature and mature DCs with peptide is far less efficient than
it is for monocytes, T and B lymphocytes, B-lymphoblastoid, melanoma and TAP
deficient T2 cells. This inefficiency of peptide transfer to the MHC molecules of
DCs makes it unlikely that these cells recycle peptides released from the MHC
molecules of other cells and may explain why cross-presentation of such peptides
has not yet been observed.
PMID- 17035347
TI - Roles of the small intestine for induction of toll-like receptor 4-mediated
innate resistance in naturally acquired murine toxoplasmosis.
AB - Peroral infection of Toxoplasma gondii is thought to reflect the typical
infection route of naturally acquired toxoplasmosis in humans. We have
investigated possible differential roles of toll-like receptor 2 (TLR2) and TLR4
in host defense against naturally acquired murine toxoplasmosis. After peroral
inoculation of T. gondii ME49 cysts, TLR4-deficient C3H/HeJ mice were more
susceptible to infection than wild-type (WT) C3H/HeN mice, as shown by increased
cyst number and low production of cytokines, which are the key factors in
protective immunity. When mice were inoculated by intra-peritoneal inoculation of
T. gondii, there were no significant differences in the number of brain cysts and
cytokine productions between C3H/HeJ and C3H/HeN mice. Histopathologic
examination revealed severe inflammation in the small intestine of C3H/HeJ (TLR4
deficient) mice, while an increased number of TLR4-positive mononuclear cells was
found in C3H/HeN (WT) mice. To confirm these phenomena, TLR2(-/-) or TLR4(-/-)
mice were infected perorally with T. gondii cysts. TLR4(-/-) mice were more
susceptible to infection compared with TLR2(-/-) and C57BL/6 mice. Nuclear factor
kappa B activation through TLR4 agonistic activity of T. gondii ME49 was
demonstrated by luciferase assay using stably expressing mouse (m) TLR2 or
mTLR4/mMD-2 transfectants. We demonstrate here for the first time that innate
immune recognition by TLR4 is involved in protective mechanisms against peroral
infection with T. gondii ME49. These results suggest that the small intestine
plays an important role in the induction of innate immunity in naturally acquired
toxoplasmosis.
PMID- 17035348
TI - Differential induction of Th1-prone immunity by human dendritic cells activated
with Sporothrix schenckii of cutaneous and visceral origins to determine their
different virulence.
AB - Sporotrichosis is caused by a thermo-dependent dimorphic fungus, Sporothrix
schenckii. The major clinical manifestations occur in the skin; however, cases of
visceral manifestations have also been increasingly reported with some being
observed in immune compromised patients. Different virulence of individual S.
schenckii strain as well as immune status of the host could contribute to form
such different clinical manifestations. Thus, the purpose of the study was to
investigate whether different virulence of individual S. schenckii could be a
factor for such clinical difference. We investigated the interactions between
human monocyte-derived dendritic cells (MoDCs) and S. schenckii, assessed by (i)
morphological features, (ii) surface marker expressions, cytokine productions,
(iii) signaling pathways and (iv) allostimulatory activity of the activated
MoDCs. Immature MoDCs, obtained from peripheral blood monocytes supplemented with
granulocyte macrophage colony-stimulating factor and IL-4, were stimulated with
S. schenckii strains of both yeasts and conidia forms of different origins
(cutaneous isolates: KMU4649, IFM5906 and IFM46010; visceral isolates: KMU4648,
IFM41598 and ATCC26331) to be used for various assays. Through the analysis, we
found that the cutaneous S. shenckii of cutaneous origins were more potent to
activate MoDCs to induce strong T(h)1 response, as evidenced by abundant IFN
gamma production, while the S. shenckii of visceral origins induced only minimal
dendritic cell activation and T(h)1 induction. The p38 mitogen-activated protein
kinase and c-Jun N-terminal kinase signaling pathways appeared to be associated
with the differential activation of the MoDCs by S. schenckii of cutaneous and
the visceral origins. Overall, we concluded that the differential activation of
MoDCs by S. schenckii of cutaneous and visceral origins to induce T(h)1 response,
other than immune status or the host, may be a factor for their different
clinical manifestations.
PMID- 17035349
TI - Diversity in lectins enables immune recognition and differentiation of wide
spectrum of pathogens.
AB - Carbohydrate-binding lectins play essential roles as pattern recognition
receptors in innate immunity in both vertebrates and invertebrates. The
carcinolectins 5 (CL5a and CL5b, the CL5 isoforms of horseshoe crab,
Carcinoscorpius rotundicauda, with apparent sizes of 36 and 40 kDa, respectively)
are prominent plasma lectins that bind all representative microbes and pathogen
associated molecular pattern molecules. Different cDNA isoforms of both CL5a and
CL5b were isolated, leading to our speculation on their functional divergence.
Characterization of CL5 isoforms bound to microbial cell surfaces demonstrates
the diversity of these lectins. The resolution patterns of the isoforms that
associate with fungus differ from those that associate with bacteria, suggesting
the unique roles these lectins play in the recognition and differentiation of
microbes. We postulate that different populations of plasma lectins act in
collaboration in frontline innate immune defense against disparate pathogens. The
functional diversity of lectins in invertebrates appears to evolutionarily
compensate for the lack of acquired immunity.
PMID- 17035350
TI - An invertebrate TNF functional analogue activates macrophages via lectin
saccharide interaction with ion channels.
AB - The invertebrate pattern-recognition protein named coelomic cytolytic factor
(CCF) and the mammalian cytokine tumor necrosis factor (TNF) share functional
analogies that are based on a similar saccharide recognition specificity. In
particular, CCF and TNF have been shown to interact with ion channels on the
surface of vertebrate cells via N,N'-diacetylchitobiose lectin-like activity. In
the present study, we show that CCF-induced membrane depolarization results in
the release of TNF, IL-6 and nitric oxide (NO) by macrophages via nuclear factor
kappaB signaling. Interestingly, our data suggest that TNF contributes, through
lectin-saccharide interaction, to the secretion of IL-6 and NO induced by CCF.
This experimental non-physiological setting based on the interaction of an
invertebrate defense lectin with vertebrate cells involved in the innate immune
response may have highlighted an evolutionarily ancient mechanism of macrophage
activation in vertebrates.
PMID- 17035351
TI - School-based health education campaign--a potential tool for social mobilization
to promote the use of DEC-fortified salt towards elimination of lymphatic
filariasis.
AB - Community compliance is crucial for the success of mass treatment using cooking
salt fortified with diethylcarbamazine citrate (DEC) for the elimination of
lymphatic filariasis (LF). We describe the role and effectiveness of school-based
health education for social mobilization to promote the use of DEC salt, in an
endemic district in India. Health education through classroom sessions was the
main motivational strategy used. Community members were targeted to receive the
message through children. The impact of this approach was assessed among students
and community members using an interviewer-administered questionnaire and
analysis of salt samples for DEC content from households. Significant improvement
in awareness on LF among students and community respondents was observed. School
health education (SHE) could promote the use of DEC salt by 19% points more in
households with children in schools covered under health education campaign
[campaign school (CS)] compared with others. Significantly higher proportion
(72.7%) of samples from households with children in CS had detectable DEC,
indicating the impact of the intervention on enhancing the use of DEC salt by the
community. The results exemplify that SHE is a potential tool for improving and
sustaining compliance, thus serving as part of a public health strategy to
eliminate LF using DEC salt.
PMID- 17035352
TI - Evaluating the properties of a stage-specific self-efficacy scale for physical
activity using classical test theory, confirmatory factor analysis and item
response modeling.
AB - The purpose of this paper was to evaluate the psychometric properties of a stage
specific self-efficacy scale for physical activity with classical test theory
(CTT), confirmatory factor analysis (CFA) and item response modeling (IRM). Women
who enrolled in the Women On The Move study completed a 20-item stage-specific
self-efficacy scale developed for this study [n=226, 51.1% African-American and
48.9% Hispanic women, mean age = 49.2 (+/-7.0) years, mean body mass index = 29.7
(+/-6.4)]. Three analyses were conducted: (i) a CTT item analysis, (ii) a CFA to
validate the factor structure and (iii) an IRM analysis. The CTT item analysis
and the CFA results showed that the scale had high internal consistency (ranging
from 0.76 to 0.93) and a strong factor structure. Results also showed that the
scale could be improved by modifying or eliminating some of the existing items
without significantly altering the content of the scale. The IRM results also
showed that the scale had few items that targeted high self-efficacy and the
stage-specific assumption underlying the scale was rejected. In addition, the IRM
analyses found that the five-point response format functioned more like a four
point response format. Overall, employing multiple methods to assess the
psychometric properties of the stage-specific self-efficacy scale demonstrated
the complimentary nature of these methods and it highlighted the strengths and
weaknesses of this scale.
PMID- 17035354
TI - Rate and polarity of gene fusion and fission in Oryza sativa and Arabidopsis
thaliana.
AB - Eukaryotic gene fusion and fission events are mechanistically more complicated
than in prokaryotes, and their quantitative contributions to genome evolution are
still poorly understood. We have identified all differentially composite or split
genes in 2 fully sequenced plant genomes, Oryza sativa and Arabidopsis thaliana.
Out of 10,172 orthologous gene pairs, 60 (0.6% of the total) revealed a verified
fusion or fission event in either lineage after the divergence of O. sativa and
A. thaliana. Polarizing these events by outgroup comparison revealed differences
in the rate of gene fission but not of gene fusion in the rice and Arabidopsis
lineages. Gene fission occurred at a higher rate than gene fusion in the O.
sativa lineage and was furthermore more common in rice than in Arabidopsis.
Nucleotide insertion bias has promoted gene fission in the O. sativa lineage,
consistent with its generally longer nucleotide sequences than A. thaliana in
selectively neutral regions, and with the abundance of transposable elements in
rice. The divergence time of monocots and dicots (140-200 Myr) indicates that
gene fusion/fission events occur at an average rate of 1x10(-11) to 2x10(-11)
events per gene per year, approximately 100-fold slower than the average per site
nuclear nucleotide substitution rate in these lineages. Gene fusion and fission
are thus rare and slow processes in higher plant genomes; they should be of
utility to address deeper evolutionary relationships among plants--and the
relationship of plants to other eukaryotic lineages--where sequence-based
phylogenies provide equivocal or conflicting results.
PMID- 17035353
TI - Evolution of the Rho family of ras-like GTPases in eukaryotes.
AB - GTPases of the Rho family are molecular switches that play important roles in
converting and amplifying external signals into cellular effects. Originally
demonstrated to control the dynamics of the F-actin cytoskeleton, Rho GTPases
have been implicated in many basic cellular processes that influence cell
proliferation, differentiation, motility, adhesion, survival, or secretion. To
elucidate the evolutionary history of the Rho family, we have analyzed over 20
species covering major eukaryotic clades from unicellular organisms to mammals,
including platypus and opossum, and have reconstructed the ontogeny and the
chronology of emergence of the different subfamilies. Our data establish that the
20 mammalian Rho members are structured into 8 subfamilies, among which Rac is
the founder of the whole family. Rho, Cdc42, RhoUV, and RhoBTB subfamilies
appeared before Coelomates and RhoJQ, Cdc42 isoforms, RhoDF, and Rnd emerged in
chordates. In vertebrates, gene duplications and retrotranspositions increased
the size of each chordate Rho subfamily, whereas RhoH, the last subfamily, arose
probably by horizontal gene transfer. Rac1b, a Rac1 isoform generated by
alternative splicing, emerged in amniotes, and RhoD, only in therians. Analysis
of Rho mRNA expression patterns in mouse tissues shows that recent subfamilies
have tissue-specific and low-level expression that supports their implication
only in narrow time windows or in differentiated metabolic functions. These
findings give a comprehensive view of the evolutionary canvas of the Rho family
and provide guides for future structure and evolution studies of other components
of Rho signaling pathways, in particular regulators of the RhoGEF family.
PMID- 17035355
TI - Impact of early lifetime trauma in later life: depression among Holocaust
survivors 60 years after the liberation of Auschwitz.
AB - RATIONALE: Holocaust survivors, who experienced trauma 60 years ago, provide an
opportunity to explore the impact of early lifetime trauma in later life and, in
particular, the interplay of depression and posttraumatic stress disorder (PTSD).
In this study, the authors contrast depressed Holocaust survivors (HD),
nondepressed Holocaust survivors (HND), and older depressed persons (CD).
METHODS: The sample consisted of 36 consecutive Holocaust survivors (mean age: 79
years) treated in a primary care practice, among whom 20 (56%) were diagnosed as
having a major depressive disorder and 16 as nondepressed; 18 depressed non
Holocaust Jewish primary care patients served as controls (mean age: 84 years).
The authors examined nine clinical and social variables. The Kruskal-Wallis, Mann
Whitney U, and chi(2) tests were used to contrast the groups. The authors used a
conservative significance level of .01. RESULTS: In contrast to the CD group, the
HD group was significantly older, more likely to report PTSD and guilt symptoms,
to have higher Beck Anxiety Inventory (BAI) and Brief Psychiatric Rating Scale
(BPRS) scores, and to have more impaired social functioning. In contrast to the
HND group, the HD group was significantly more likely to report PTSD and guilt
feelings, to have higher Hamilton Depression Scale (HAM-D), BAI, and BPRS scores,
and to have more impaired social functioning. In contrast to the CD group, the
HND group was significantly more likely to have PTSD symptoms and to have lower
HAM-D and BPRS scores. CONCLUSIONS: The prevalence of depression and PTSD
symptoms were very high among survivors. Depressed survivors had significantly
worse psychologic and social functioning than depressed controls. Depressed
survivors had more PTSD symptoms than nondepressed survivors, although it is
unclear as to the causal direction of the relationship between depression and
PTSD.
PMID- 17035356
TI - Risk and protective factors for psychopathology among older versus younger adults
after the 2004 Florida hurricanes.
AB - OBJECTIVE: Previous research demonstrates increased resiliency to psychopathology
after disasters among older adults. However, little is known about differences in
age-based risk and protective factors for postdisaster mental illness. METHOD:
The authors used random-digit dialing methodology to survey 1,130 older adults
(60+ years) and 413 younger adults residing in Florida counties directly affected
by the 2004 hurricanes. Assessed risk and protective factors included
demographics, social support, displacement, incurred dollar losses, perceived
positive outcomes, and self-rated health status. Outcome variables included
symptom counts of Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition-defined posttraumatic stress disorder (PTSD), major depressive disorder
(MDD), and generalized anxiety disorder (GAD). RESULTS: Older adults reported
fewer symptoms of PTSD, MDD, and GAD. Explanatory risk variables accounted for
large proportions of variance, but differed in meaningful ways across age groups.
CONCLUSION: Although older adults are less symptomatic, their psychologic
reactions appear more closely connected to economic consequences of disasters.
PMID- 17035357
TI - The coccolithovirus microarray: an array of uses.
AB - The Coccolithoviridae is a recently discovered family of giant algal viruses.
Here, we review the genomic and transcriptomic characterization of this family
based on the results generated from a coccolithovirus microarray. The microarray
has been used to aid the annotation of the genome, to investigate the infection
process at the transcriptional level and to assess the diversity in genomic
content within the family.
PMID- 17035358
TI - The Consortium on the Genetics of Endophenotypes in Schizophrenia: model
recruitment, assessment, and endophenotyping methods for a multisite
collaboration.
AB - BACKGROUND: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing,
National Institute of Mental Health-funded, 7-site collaboration investigating
the occurrence and genetic architecture of quantitative endophenotypes related to
schizophrenia. The purpose of this article is to provide a description of the
COGS structure and methods, including participant recruitment and assessment.
METHODS: The hypothesis-driven recruitment strategy ascertains families that
include a proband with a Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition diagnosis of schizophrenia, and at least one unaffected full
sibling available for genotyping and endophenotyping, along with parents
available for genotyping and (optional depending on age) endophenotyping. The
family structure is selected to provide contrast in quantitative endophenotypic
traits and thus to maximize the power of the planned genetic analyses. Probands
are recruited from many sources including clinician referrals, local National
Alliance for the Mentally Ill chapters, and advertising via the media. All
participants undergo a standardized protocol that includes clinical
characterization, a blood draw for genotyping, and endophenotype assessments (P50
suppression, prepulse inhibition, antisaccade performance, continuous performance
tasks, letter-number span, verbal memory, and a computerized neurocognitive
battery). Investigators participate in weekly teleconferences to coordinate and
evaluate recruitment, clinical assessment, endophenotyping, and continuous
quality control of data gathering and analyses. Data integrity is maintained
through use of a highly quality-assured, centralized web-based database. RESULTS:
As of February 2006, 355 families have been enrolled and 688 participants have
been endophenotyped, including schizophrenia probands (n = 154, M:F = 110:44),
first-degree biological relatives (n = 343, M:F = 151:192), and community
comparison subjects (n = 191, M:F = 81:110). DISCUSSION: Successful multisite
genetics collaborations must institute standardized methodological criteria for
assessment and recruitment that are clearly defined, well communicated, and
uniformly applied. In parallel, studies utilizing endophenotypes require strict
adherence to criteria for cross-site data acquisition, equipment calibration and
testing and software equivalence, and continuous quality assurance for many
measures obtained across sites. This report describes methods and presents the
structure of the COGS as a model of multisite endophenotype genetic studies. It
also provides demographic information after the first 2 years of data collection
on a sample for whom the behavioral data and genetics of endophenotype
performance will be fully characterized in future articles. Some issues discussed
in the reviews that follow reflect the challenges of evaluating endophenotypes in
studies of the genetic architecture of endophenotypes in schizophrenia.
PMID- 17035359
TI - Statistical genetics concepts and approaches in schizophrenia and related
neuropsychiatric research.
AB - Statistical genetics is a research field that focuses on mathematical models and
statistical inference methodologies that relate genetic variations (ie, naturally
occurring human DNA sequence variations or "polymorphisms") to particular traits
or diseases (phenotypes) usually from data collected on large samples of families
or individuals. The ultimate goal of such analysis is the identification of genes
and genetic variations that influence disease susceptibility. Although of extreme
interest and importance, the fact that many genes and environmental factors
contribute to neuropsychiatric diseases of public health importance (eg,
schizophrenia, bipolar disorder, and depression) complicates relevant studies and
suggests that very sophisticated mathematical and statistical modeling may be
required. In addition, large-scale contemporary human DNA sequencing and related
projects, such as the Human Genome Project and the International HapMap Project,
as well as the development of high-throughput DNA sequencing and genotyping
technologies have provided statistical geneticists with a great deal of very
relevant and appropriate information and resources. Unfortunately, the use of
these resources and their interpretation are not straightforward when applied to
complex, multifactorial diseases such as schizophrenia. In this brief and largely
nonmathematical review of the field of statistical genetics, we describe many of
the main concepts, definitions, and issues that motivate contemporary research.
We also provide a discussion of the most pressing contemporary problems that
demand further research if progress is to be made in the identification of genes
and genetic variations that predispose to complex neuropsychiatric diseases.
PMID- 17035360
TI - Effect of stochastic synaptic and dendritic dynamics on synaptic plasticity in
visual cortex and hippocampus.
AB - Various forms of synaptic plasticity, including spike timing-dependent
plasticity, can be accounted for by calcium-dependent models of synaptic
plasticity. However, recent results in which synaptic plasticity is induced by
multi-spike protocols cannot simply be accounted for by linear superposition of
plasticity due to spike pairs or by existing calcium-dependent models. In this
paper, we show that multi-spike protocols can be accounted for if, in addition to
the dynamics of back-propagating action potentials, stochastic synaptic dynamics
are taken into account. We show that a stochastic implementation can account for
the data better than a deterministic implementation and is also more robust. Our
results demonstrate that differences between experimental results obtained in
hippocampus and visual cortex can be accounted for by the different synaptic and
dendritic dynamics in these two systems.
PMID- 17035361
TI - Partial reconstruction of muscle activity from a pruned network of diverse motor
cortex neurons.
AB - Primary motor cortex (M1) neurons traditionally have been viewed as "upper motor
neurons" that directly drive spinal motoneuron pools, particularly during finger
movements. We used spike-triggered averages (SpikeTAs) of electromyographic (EMG)
activity to select M1 neurons whose spikes signaled the arrival of input in
motoneuron pools, and examined the degree of similarity between the activity
patterns of these M1 neurons and their target muscles during 12 individuated
finger and wrist movements. Neuron-EMG similarity generally was low. Similarity
was unrelated to the strength of the SpikeTA effect, to whether the effect was
pure versus synchrony, or to the number of muscles influenced by the neuron.
Nevertheless, the sum of M1 neuron activity patterns, each weighted by the sign
and strength of its SpikeTA effect, could be more similar to the EMG than the
average similarity of individual neurons. Significant correlations between the
weighted sum of M1 neuron activity patterns and EMG were obtained in six of 17
muscles, but showed R(2) values ranging from only 0.26 to 0.42. These
observations suggest that additional factors-including inputs from sources other
than M1 and nonlinear summation of inputs to motoneuron pools-also contributed
substantially to EMG activity patterns. Furthermore, although each of these M1
neurons produced SpikeTA effects with a significant peak or trough 6-16 ms after
the triggering spike, shifting the weighted sum of neuron activity to lead the
EMG by 40-60 ms increased their similarity, suggesting that the influence of M1
neurons that produce SpikeTA effects includes substantial synaptic integration
that in part may reach the motoneuron pools over less-direct pathways.
PMID- 17035362
TI - Duration-dependent response of SI to vibrotactile stimulation in squirrel monkey.
AB - In previous studies, we showed that the spatial and intensive aspects of the SI
response to skin flutter stimulation are modified systematically as stimulus
amplitude is increased. In this study, we examined the effects of duration of
skin flutter stimulation on the spatiotemporal characteristics of the response of
SI cortex. Optical intrinsic signal (OIS) imaging was used to study the evoked
response in SI of anesthetized squirrel monkeys to 25-Hz sinusoidal vertical skin
displacement stimulation. Four stimulus durations were tested (0.5, 1.0, 2.0, and
5.0 s); all stimuli were delivered to a discrete site on the glabrous skin of the
contralateral forelimb. Skin stimulation evoked a prominent increase in
absorbance within the forelimb regions in SI of the contralateral hemisphere.
Responses to brief (0.5 s) stimuli were weaker and spatially more extensive than
responses to longer duration stimuli (1.0, 2.0, and 5.0 s). Stimuli >or=1 s in
duration suppressed responses to below background levels (decreased absorbance)
in regions that surrounded the maximally activated region. The magnitude of the
suppression in the surrounding regions was nonuniform and usually was strongest
medial and posterior to the maximally activated region. The results show that
sustained (>or=1.0 s) stimulation decreases the spatial extent of the responding
SI cortical population. Registration of the optical responses with the previously
documented SI topographical organization strongly suggests that the cortical
regions that undergo the strongest suppression represent skin sites that are
normally co-stimulated during tactile exploration.
PMID- 17035363
TI - 7-12 Hz high-voltage rhythmic spike discharges in rats evaluated by antiepileptic
drugs and flicker stimulation.
AB - Paroxysmal 7- to 12-Hz high-voltage rhythmic spike (HVRS) or spike-wave
discharges often appear in several particular strains of rats. However,
functional hypotheses of these 7-12 Hz high-voltage cortical oscillations
(absence seizure vs. idling mu rhythm) are inconclusive. The mu rhythm can be
provoked by flicker stimulation (FS) in most people, but FS is less effective at
eliciting absence epileptic activity. Therefore FS and antiepileptic drugs were
used to verify the role of HVRS activity in Long-Evans rats with spontaneous HVRS
discharges and Wistar rats without spontaneous HVRS discharges. The occurrence of
HVRS discharges was significantly reduced by antiabsence drugs (ethosuximide,
valproic acid, and diazepam) in dose-dependent manners, but high-dose
carbamazepine displayed little effect. On the other hand, oscillation frequencies
and durations of spontaneous HVRS discharges were not altered by FS. Under
asynchronous brain activity, many FSs (>60%) elicited small-amplitude mu-rhythm
like activity in the barrel cortex concomitant with FS-related rhythms in the
occipital cortex and resulted in significant augmentation of 7-12 Hz power in the
parietal region. Furthermore, a large portion of FSs (>60%) revealed increase of
7-12 Hz power of the parietal cortex after ethosuximide administration (100 mg/kg
ip) in Long-Evans rats. Similar FS-elicited phenomena also appeared in Wistar
rats. Characteristics of FS-elicited mu-rhythm-like activities were consistent
with those observed in humans, and they remarkably differed from those of
spontaneous HVRS discharges. These results support the hypothesis that HVRS
activity in Long-Evans rats may be an absence-like seizure activity rather than
the mu rhythm.
PMID- 17035364
TI - Persistent enhancement of neuron-glia signaling mediated by increased
extracellular K+ accompanying long-term synaptic potentiation.
AB - Neuron-glia signaling is important for neural development and functions. This
signaling may be regulated by neuronal activity and undergo modification similar
to long-term potentiation (LTP) of neuronal synapses, a hallmark of neuronal
plasticity. We found that tetanic stimulation of Schaffer collaterals (Sc) in the
hippocampus that induced LTP in neurons also resulted in LTP-like persistent
elevation of Sc-evoked slow depolarization in perisynaptic astrocytes. The
elevated slow depolarization in astrocytes was abolished by NMDA receptor
antagonist and K(+) channel inhibitors, but not by Ca(2+) chelator BAPTA loaded
in the recorded astrocytes, suggesting involvement of an increased extracellular
K(+) accumulation accompanying LTP of neuronal synapses. The increased K(+)
accumulation and astrocyte depolarization after LTP induction may reduce the
efficiency of glial glutamate transporters, which may contribute to the enhanced
synaptic efficacy. The neuronal activity-induced persistent enhancement of neuron
glia signaling may thus have important physiological relevance.
PMID- 17035365
TI - Acutely dissociated sensory neurons: normal or neuropathic? Focus on:
"Dissociation of dorsal root ganglion neurons induces hyperexcitability that is
maintained by increased responsiveness to cAMP and cGMP".
PMID- 17035367
TI - Sound localization during homotopic and heterotopic bilateral cooling
deactivation of primary and nonprimary auditory cortical areas in the cat.
AB - Although the contributions of primary auditory cortex (AI) to sound localization
have been extensively studied in a large number of mammals, little is known of
the contributions of nonprimary auditory cortex to sound localization. Therefore
the purpose of this study was to examine the contributions of both primary and
all the recognized regions of acoustically responsive nonprimary auditory cortex
to sound localization during both bilateral and unilateral reversible
deactivation. The cats learned to make an orienting response (head movement and
approach) to a 100-ms broad-band noise stimulus emitted from a central speaker or
one of 12 peripheral sites (located in front of the animal, from left 90 degrees
to right 90 degrees , at 15 degrees intervals) along the horizontal plane after
attending to a central visual stimulus. Twenty-one cats had one or two bilateral
pairs of cryoloops chronically implanted over one of ten regions of auditory
cortex. We examined AI [which included the dorsal zone (DZ)], the three other
tonotopic fields [anterior auditory field (AAF), posterior auditory field (PAF),
ventral posterior auditory field (VPAF)], as well as six nontonotopic regions
that included second auditory cortex (AII), the anterior ectosylvian sulcus
(AES), the insular (IN) region, the temporal (T) region [which included the
ventral auditory field (VAF)], the dorsal posterior ectosylvian (dPE) gyrus
[which included the intermediate posterior ectosylvian (iPE) gyrus], and the
ventral posterior ectosylvian (vPE) gyrus. In accord with earlier studies,
unilateral deactivation of AI/DZ caused sound localization deficits in the
contralateral field. Bilateral deactivation of AI/DZ resulted in bilateral sound
localization deficits throughout the 180 degrees field examined. Of the three
other tonotopically organized fields, only deactivation of PAF resulted in sound
localization deficits. These deficits were virtually identical to the unilateral
and bilateral deactivation results obtained during AI/DZ deactivation. Of the six
nontonotopic regions examined, only deactivation of AES resulted in sound
localization deficits in the contralateral hemifield during unilateral
deactivation. Although bilateral deactivation of AI/DZ, PAF, or AES resulted in
profound sound localization deficits throughout the entire field, the cats were
generally able to orient toward the hemifield that contained the acoustic
stimulus, but not accurately identify the location of the stimulus. Neither
unilateral nor bilateral deactivation of areas AAF, VPAF, AII, IN, T, dPE, nor
vPE had any effect on the sound localization task. Finally, bilateral heterotopic
deactivations of AI/DZ, PAF, or AES yielded deficits that were as profound as
bilateral homotopic cooling of any of these sites. The fact that deactivation of
any one region (AI/DZ, PAF, or AES) was sufficient to produce a deficit indicated
that normal function of all three regions was necessary for normal sound
localization. Neither unilateral nor bilateral deactivation of AI/DZ, PAF, or AES
affected the accurate localization of a visual target. The results suggest that
hemispheric deactivations contribute independently to sound localization
deficits.
PMID- 17035366
TI - Complementary postsynaptic activity patterns elicited in olfactory bulb by
stimulation of mitral/tufted and centrifugal fiber inputs to granule cells.
AB - Main olfactory bulb (MOB) granule cells receive spatially segregated
glutamatergic synaptic inputs from the dendrites of mitral/tufted cells as well
as from the axons of centrifugal fibers (CFFs) originating in olfactory cortical
areas. Dendrodendritic synapses from mitral/tufted cells occur on granule cell
distal dendrites in the external plexiform layer (EPL), whereas CFFs
preferentially target the somata/proximal dendrites of granule cells in the
granule cell layer (GCL). In the present study, tract tracing, and recordings of
field potentials and voltage-sensitive dye optical signals were used to map
activity patterns elicited by activation of these two inputs to granule cells in
mouse olfactory bulb slices. Stimulation of the lateral olfactory tract (LOT)
produced a negative field potential in the EPL and a positivity in the GCL. CFF
stimulation produced field potentials of opposite polarity in the EPL and GCL to
those elicited by LOT. LOT-evoked optical signals appeared in the EPL and spread
subsequently to deeper layers, whereas CFF-evoked responses appeared in the GCL
and then spread superficially. Evoked responses were reduced by N-methyl-d
aspartate (NMDA) receptor antagonists and completely suppressed by AMPA receptor
antagonists. Reduction of extracellular Mg(2+) enhanced the strength and
spatiotemporal extent of the evoked responses. These and additional findings
indicate that LOT- and CFF-evoked field potentials and optical signals reflect
postsynaptic activity in granule cells, with moderate NMDA and dominant AMPA
receptor components. Taken together, these results demonstrate that LOT and CFF
stimulation in MOB slices selectively activate glutamatergic inputs to the distal
dendrites versus somata/proximal dendrites of granule cells.
PMID- 17035368
TI - Uncovering host defences in the urinary tract: cathelicidin and beyond.
PMID- 17035369
TI - The potential of matrix metalloproteinase-2 as a marker of peritoneal injury,
increased solute transport, or progression to encapsulating peritoneal sclerosis
during peritoneal dialysis--a multicentre study in Japan.
AB - BACKGROUND: Long-term peritoneal dialysis (PD) leads to peritoneal injury. At
worst, peritoneal injury leads to encapsulating peritoneal sclerosis (EPS), which
is a serious complication of PD. The mortality rate of EPS is extremely high. To
perform PD safely, monitoring of peritoneal injury that leads to EPS is a
necessity. METHODS: A total of 444 PD patients with end-stage renal disease at 60
centres in Japan were analysed (sex, 54% males; median age, 56 years; median PD
duration, 55 months). Matrix metalloproteinase (MMP)-2 and MMP-9 in the
peritoneal effluents were analysed with gelatin zymography or enzyme-linked
immunosorbent assay. Cells expressing MMP-2 in the peritoneal tissue were
investigated immunohistologically with anti-MMP-2 antibodies. Peritoneal solute
transport was assessed with the peritoneal equilibration test (PET). RESULTS: The
MMP-2 levels in peritoneal effluents obtained with the PET were significantly
correlated with the D/P Cr ratio (R = 0.69, P < 0.001) and the D/D0 glucose ratio
(R = -0.59, P < 0.001). The MMP-2 levels in patients with mild peritoneal injury,
moderate peritoneal injury, severe peritoneal injury (EPS) and infectious
peritonitis were significantly higher than those in control patients (P < 0.001,
P < 0.001, P < 0.01 and P < 0.05, respectively). MMP-2 was produced by
myofibroblast-like mesenchymal cells and macrophages in the peritoneum. The
peritoneal effluents from patients with infectious peritonitis showed strong MMP
9 signals. CONCLUSIONS: From these results, MMP-2 levels in peritoneal effluents
reflect peritoneal solute transport and changes in MMP-2 levels are associated
with peritoneal injury that leads to EPS. MMP-2 may be a useful marker of
peritoneal injury, increased solute transport or progression to EPS.
PMID- 17035370
TI - Inequality of renal replacement therapy in the low-income countries.
PMID- 17035371
TI - Serum phosphate and outcomes in PD patients.
PMID- 17035373
TI - Ultrapure dialysis fluid--how pure is it and do we need it?
PMID- 17035374
TI - Drugs as a hidden source of aluminium for chronic renal patients.
PMID- 17035375
TI - Adherence to peritoneal dialysis training schedule.
AB - BACKGROUND: Shortening behaviour during peritoneal dialysis training can be
easily measured, and likened to the skipping behaviour in haemodialysis subjects,
although its effect on peritoneal dialysis outcomes is now well understood. We
studied the clinical impact of failing to adhere to a peritoneal dialysis
training programme among incident dialysis patients. METHODS: This study included
159 consecutive inception peritoneal dialysis patients in a single centre from
September 1999 through November 2002. We evaluated the effects of behavioural
compliance quantified by the per cent time arriving late for scheduled peritoneal
dialysis training. The patients were categorized by whether they arrived late in
>20% of their peritoneal dialysis training sessions. RESULTS: Of the 159 incident
peritoneal dialysis patients (mean age 57 +/- 13 years) who attended peritoneal
dialysis training, 70 subjects (44%) arrived late in >20% of the sessions. They
were younger by 5 years than patients who arrived late < or =20%. Mean
peritonitis-free time for subjects who arrived late for training in >20% the of
sessions was 30.9 months, as compared with 41.8 months in subjects with < or =20%
late attendance behaviour (log rank test, P = 0.038). Multivariable Cox
proportional hazards analysis showed that late attendance behaviour and baseline
serum albumin were the only independent risk factors for the time to a first
peritonitis after adjustment for diabetes mellitus and relevant coexisting
medical factors. Late arrival in >20% of the peritoneal dialysis training
sessions was associated with >50% increased likelihood of subsequent peritonitis,
with an adjusted risk ratio of 1.56 (95% confidence interval, 1.02-2.39; P =
0.04). CONCLUSION: These findings show that the behavioural measure of late
attendance for peritoneal dialysis training has a crucial role in predicting
peritonitis. It may therefore represent a practical strategy for identifying poor
adherence or predicting medical outcomes.
PMID- 17035376
TI - How to tackle the avalanche of chronic kidney disease in sub-Saharan Africa: the
situation in the Democratic Republic of Congo as an example.
PMID- 17035377
TI - Decreased renal transplant function after parathyroidectomy.
AB - BACKGROUND: Persistent secondary hyperparathyroidism after renal transplantation
may require parathyroidectomy (PTX). Clinical experience suggests that these
patients commonly develop decreased renal function thereafter. METHODS: To test
this notion, we evaluated 76 transplant patients who underwent pararhyroidectomy
between 1997 and 2003. RESULTS: In half the patients (47%), creatinine clearance
decreased >20% (before vs after PTX, 57 +/- 21 vs 38 +/- 17 ml/min, P = 0.001).
The patients with decreased creatinine clearance had higher parathyroid hormone
(PTH) concentrations before and lower values after PTX compared with those who
did not (594 +/- 392 vs 447 +/- 234 pg/ml before PTX, P = 0.03; 35 vs 123 pg/ml
thereafter, P = 0.002). They also had lower serum calcium concentrations after
PTX (2.0 vs 2.2 mmol/l, P = 0.005) and they required more calcium and vitamin D
analogues. These patients also more commonly underwent total PTX with
autotransplantation, compared with subtotal (75 vs 50%, P = 0.03). However, in
multivariate analysis, only the delta PTH decline (%) after PTX was a significant
predictor of deteriorating renal function (P = 0.005) and was correlated with the
creatinine clearance decrease (R = 0.369, P = 0.001). Prospectively measured
inulin and para-amino-hippuric acid (PAH) clearance decreased significantly after
PTX in a subgroup of 19 patients (inulin before vs after PTX 67 vs 55 ml/min/1.73
m(2), P = 0.001; PAH 360 vs 289 ml/min/1.73 m(2), P = 0.001). Transplant biopsies
revealed calcification in 70% of biopsied cases. CONCLUSION: Since PTH has a
known positive regulatory effect on renal perfusion and glomerular filtration
rate, we conclude that relative hypoparathyroidism after PTX is the main
mechanism contributing to decreased renal function in these patients. There was
no difference in 10-year-graft survival between the deteriorating and the non
deteriorating group.
PMID- 17035378
TI - Nephrotic syndrome with spontaneous anticoagulant activity.
PMID- 17035379
TI - The long and winding road of diet and breast cancer prevention.
PMID- 17035380
TI - Genetic susceptibility to aggressive prostate cancer.
PMID- 17035381
TI - The enigmatic epidemiology of nasopharyngeal carcinoma.
AB - Nasopharyngeal carcinoma (NPC) has a unique and complex etiology that is not
completely understood. Although NPC is rare in most populations, it is a leading
form of cancer in a few well-defined populations, including natives of southern
China, Southeast Asia, the Arctic, and the Middle East/North Africa. The
distinctive racial/ethnic and geographic distribution of NPC worldwide suggests
that both environmental factors and genetic traits contribute to its development.
This review aims to summarize the current knowledge regarding the epidemiology of
NPC and to propose new avenues of research that could help illuminate the causes
and ultimately the prevention of this remarkable disease. Well-established risk
factors for NPC include elevated antibody titers against the Epstein-Barr virus,
consumption of salt-preserved fish, a family history of NPC, and certain human
leukocyte antigen class I genotypes. Consumption of other preserved foods,
tobacco smoking, and a history of chronic respiratory tract conditions may be
associated with elevated NPC risk, whereas consumption of fresh fruits and
vegetables and other human leukocyte antigen genotypes may be associated with
decreased risk. Evidence for a causal role of various inhalants, herbal
medicines, and occupational exposures is inconsistent. Other than dietary
modification, no concrete preventive measures for NPC exist. Given the unresolved
gaps in understanding of NPC, there is a clear need for large-scale, population
based molecular epidemiologic studies to elucidate how environmental, viral, and
genetic factors interact in both the development and the prevention of this
disease.
PMID- 17035382
TI - The case for a genetic predisposition to serrated neoplasia in the colorectum:
hypothesis and review of the literature.
AB - In recent years, an alternative pathway of colorectal cancer development has been
described in which serrated polyps replace the traditional adenoma as the
precursor lesion. Importantly, serrated polyps and a subset of colorectal cancer
show largely nonoverlapping mutation profiles to those found in adenomas and the
majority of colorectal cancer. These genetic alterations include activating
mutation of the BRAF proto-oncogene and widespread gene promoter hypermethylation
(CpG island methylator phenotype or CIMP). Up to 15% of colorectal cancer is
likely to develop on the basis of a strong genetic predisposition. The two most
well-characterized syndromes, familial adenomatous polyposis and hereditary
nonpolyposis colorectal cancer (Lynch syndrome), both develop via the adenoma
carcinoma pathway and together account for approximately one third of familial
colorectal cancer. We have recently described 11 families in which there is
evidence that the genetic predisposition to autosomal dominant colorectal cancer
is linked to the serrated pathway. This condition, serrated pathway syndrome, and
the related condition, hyperplastic polyposis, the presentation of which suggests
a recessive mode of inheritance, represent two syndromes in which BRAF mutation
and methylation co-occur within serrated precursor lesions. Further, CIMP is
observed in the normal colonic mucosa of individuals with hyperplastic polyposis
consistent with a field defect in epigenetic regulation. The spectrum of serrated
neoplasia may also implicate the apparently sporadic and later onset subset of
colorectal cancer with high levels of microsatellite instability. The tendency
for these lesions to be multiple, associated with smoking, and to show frequent
BRAF mutation and CIMP points to a defect that may result from interactions
between the environment and a weakly penetrant genetic alteration.
PMID- 17035383
TI - Nonsteroidal anti-inflammatory drugs and subsite-specific colorectal cancer
incidence in the Iowa women's health study.
AB - BACKGROUND: Previous epidemiologic studies have shown that regular use of
nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with decreased
colorectal cancer risk. However, few studies have examined associations between
NSAID use and subsite-specific colorectal cancer risks. Because tumors of the
proximal and distal colon differ with respect to their genetic alterations,
clinicopathologic features, and demographic distribution, further investigation
of subsite-specific colorectal cancer risks may be rewarding. METHODS: Data about
aspirin and non-aspirin-NSAID use were recorded by self-report in 1992 among the
initially cancer-free cohort of postmenopausal women in the Iowa Women's Health
Study (n = 27,160). In total, 637 women developed colorectal cancer during the 11
years of follow-up, including 365 proximal colon, 132 distal colon, and 120
rectal cancer cases (11 overlapping and 9 not specified). RESULTS: For colon
cancer, the multivariable-adjusted hazard ratios (HR) for women reporting use of
aspirin two to five times and six or more times weekly (compared with nonusers of
aspirin) were 0.79 [95% confidence interval (95% CI), 0.59-1.04] and 0.76 (95%
CI, 0.58-1.00), respectively. The corresponding HRs for non-aspirin NSAIDs were
0.63 (95% CI, 0.41-0.96) and 0.85 (95% CI, 0.63-1.15), respectively. For proximal
colon cancer, the multivariable-adjusted HRs for women reporting use of aspirin
or non-aspirin NSAIDs two or more times weekly (compared with nonusers of each)
were 0.67 (95% CI, 0.51-0.87) and 0.71 (95% CI, 0.52-0.97), respectively. No
statistically significant association was found between either distal colon or
rectal cancer and aspirin or non-aspirin NSAID use. DISCUSSION: Our study is
consistent with a limited number of prior reports that have observed stronger
associations between NSAID use and proximal versus distal colorectal cancer.
PMID- 17035384
TI - Risk of colorectal cancer is linked to erythrocyte compositions of fatty acids as
biomarkers for dietary intakes of fish, fat, and fatty acids.
AB - Consumption of fish rich in n-3 polyunsaturated fatty acids (PUFAs), such as
docosahexaenoic acid, is suggested to reduce colorectal cancer risk through
inhibition of the arachidonic acid (AA) cascade related to tumorigenesis and cell
proliferation. High intake of saturated fatty acids (SFAs) may increase the risk.
To examine associations between colorectal cancer risk and fatty acid
compositions in erythrocyte membranes, as biomarkers for dietary intakes of fish,
fat, and fatty acids, we conducted a case-control study with 74 incident cases
and 221 noncancer controls (matched by age, sex, and season of sample
collection). Erythrocyte fatty acids were measured using an accelerated solvent
extraction and a gas-liquid chromatography. Colorectal cancer had no association
with dietary intakes of meat, fish, fat, and fatty acids. However, the risk was
inversely associated with erythrocyte compositions of docosahexaenoic acid, AA,
and PUFAs [the highest to the lowest tertile, odds ratios, 0.36, 0.42, and 0.15;
95% confidence intervals, 0.14-0.93, 0.18-0.95, and 0.05-0.46; P(trend) < 0.05,
respectively] and positively with those of palmitic acid, SFAs, and the ratio of
SFAs/PUFAs (odds ratios, 6.46, 8.20, and 9.45; 95% confidence intervals, 2.41
17.26, 2.86-23.52, and 2.84-31.43; P(trend) < 0.005, respectively). In
conclusion, we could clearly show decreased and increased risks for colorectal
cancer related to PUFAs and SFAs compositions in erythrocyte membranes,
respectively, but further research is needed to investigate the discrepancy
between our findings and the generally accepted role of the AA cascade.
PMID- 17035385
TI - Comparison of polymorphisms in genes involved in polycyclic aromatic hydrocarbon
metabolism with urinary phenanthrene metabolite ratios in smokers.
AB - The hypothesis that interindividual differences among smokers in the metabolism
of polycyclic aromatic hydrocarbons (PAH) are related to lung cancer risk has
been extensively investigated in the literature. These studies have compared lung
cancer risk in groups of smokers with or without polymorphisms in genes involved
in PAH metabolism. We believe that carcinogen metabolite phenotyping, involving
the actual measurement of PAH metabolites, would be a better way to investigate
differences in lung cancer risk. With this goal in mind, we have developed
methods for quantifying phenanthrene metabolites in urine. Phenanthrene is the
simplest PAH with a bay region, a feature closely associated with
carcinogenicity. The urinary metabolite r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4
tetrahydrophenanthrene (PheT) is a measure of metabolic activation, whereas
phenanthrols (HOPhe) are a measure of detoxification. In this study, we
quantified urinary PheT/HOPhe ratios in 346 smokers who were also genotyped for
11 polymorphisms in genes involved in PAH metabolism: CYP1A1MspI, CYP1A1I462V,
CYP1B1R48G, CYP1B1A119S, CYP1B1L432V, CYP1B1N453S, EPHX1Y113H, EPHX1H139R,
GSTP1I105V, GSTP1A114V, and GSTM1 null. The geometric mean molar PheT/3-HOPhe
ratio was 4.08 (95% confidence interval, 3.79-4.39). Ten percent of the smokers
had PheT/3-HOPhe ratios of > or =9.90. We found a significant association between
the presence of the CYP1A1I462V polymorphism and high PheT/3-HOPhe ratios (P =
0.02). This effect was particularly strong in females and in combination with the
GSTM1 null polymorphism. In contrast, the CYP1B1R48G and CYP1B1A119S
polymorphisms were associated with significantly lower PheT/3-HOPhe ratios,
particularly in Blacks. There were no consistent significant effects of any of
the other polymorphisms on PheT/3-HOPhe ratios. The highest 10% of PheT/3-HOPhe
ratios could not be predicted by the presence of any of the 11 polymorphisms
individually or by certain combinations. The effects of the CYP1A1I462
polymorphism observed here, particularly in combination with GSTM1 null, are
quite consistent with reports in the literature. However, the results of this
study indicate that genotyping is not an effective way to predict PAH metabolism
at least as represented by PheT/HOPhe ratios.
PMID- 17035386
TI - CYP2A6 genotype, phenotype, and the use of nicotine metabolites as biomarkers
during ad libitum smoking.
AB - CYP2A6 inactivates nicotine to cotinine and cotinine to 3-hydroxycotinine. We
investigated which of plasma nicotine and metabolites were most related to CYP2A6
genotype and smoking levels. We assessed demographic and smoking histories in 152
Caucasian ad libitum smokers, measured breath carbon monoxide (CO) levels, and
determined plasma nicotine, cotinine, and 3-hydroxycotinine by high-performance
liquid chromatography and CYP2A6 genotypes by PCR. Cigarettes per day was most
closely related to CO (r = 0.60, P < 0.001) followed by plasma cotinine (r =
0.53, P < 0.001), whereas plasma cotinine was most strongly correlated with CO
levels (r = 0.74, P < 0.001), confirming that cotinine is a good indicator of
smoking levels; this was not limited by CYP2A6 variants. 3
Hydroxycotinine/cotinine is reported to be a good marker of CYP2A6 activity, and
we found that the 3-hydroxycotinine/(cotinine + nicotine) ratio was most
correlated with CYP2A6 genotype (r = 0.38, P < 0.001). Inclusion of the
CYP2A6*12A allele strengthened the correlation (r = 0.46, P < 0.001), suggesting
that the identification of novel alleles will continue to improve this
relationship. Nicotine metabolism is slower in smokers, and we have shown that
CYP2A6 is reduced by nicotine treatment in monkeys. Here, we found that plasma
nicotine levels were inversely correlated with CYP2A6 activity (3
hydroxycotinine/cotinine, r = -0.41, P < 0.001) among those without CYP2A6
variants, suggesting a reduction in metabolism with higher nicotine levels.
Together, these findings (a) confirm the use of plasma cotinine and CO as
indicators of Caucasians' smoking levels, and that this is not limited by CYP2A6
genetic variation; (b) indicate that 3-hydroxycotinine/cotinine and 3
hydroxycotinine/(cotinine + nicotine) are moderately good indicators of the
CYP2A6 genotype; and (c) support that nicotine exposure may reduce its own
metabolism.
PMID- 17035387
TI - Maternal smoking and testicular germ cell tumors.
AB - Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15
to 35 years in the United States. The well-established TGCT risk factors
cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer
indicate that exposures in early life and/or in the familial setting may be
critical to determining risk. Previous reports of familial clustering of lung
cancer in mothers and testicular cancers in sons suggest that passive smoking in
childhood may be such an exposure. To clarify the relationship of passive smoking
exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the
Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were
analyzed. Data from 1,086 mothers of the cases and controls were also examined.
Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95%
confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8
1.3) and TGCT risk. Although living with a non-parent smoker was marginally
related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number
of smokers, amount smoked, or duration of smoking. Responses from both case
control participants and mothers also revealed no relationship between either
maternal smoking while pregnant or while breast-feeding. Results did not differ
by TGCT histology (seminoma, non-seminoma). These results do not support the
hypothesis that passive smoking, either in utero or in childhood, is related to
risk of TGCT. Other early life exposures, however, may explain the familial
clustering of lung cancer in mothers and TGCT in sons.
PMID- 17035388
TI - Validity of self-reported smoking status among participants in a lung cancer
screening trial.
AB - Lung cancer remains a devastating disease associated with substantial morbidity
and mortality. Recent research has suggested that lung cancer screening with
spiral computed tomography scans might reduce lung cancer mortality. Studies of
lung cancer screening have also suggested that significant numbers of
participants quit smoking after screening. However, most have relied solely on
self-reported smoking behavior, which may be less accurate among participants in
lung cancer screening. To assess the validity of self-reported smoking status
among participants in a lung cancer screening trial, this study compared self
reported smoking status against urinary cotinine levels. The sample included 55
consecutive participants enrolled in a randomized clinical trial comparing annual
spiral computed tomography and chest X-ray for lung cancer screening.
Participants were a mean of 59 years of age and predominantly Caucasian (96%) and
male (55%). Self-reported smoking status was assessed before and after
participants learned of the purpose of the biochemical verification study. Using
urinary cotinine as the "gold standard," the sensitivity and specificity of self
reported smoking status were 91% and 95%, respectively (kappa = 0.85, P < 0.001,
95% confidence interval = 0.71-0.99). Total misclassification rate was 7%.
However, three of the four misclassified participants reported concurrent use of
nicotine replacement strategies. Eliminating these cases from the analysis
revealed sensitivity of 100% and specificity of 95% (kappa = 0.96, P < 0.001, 95%
confidence interval = 0.88-1.00). In conclusion, self-reported smoking status
among participants in a lung cancer screening trial was highly consistent with
urinary cotinine test results.
PMID- 17035389
TI - Marijuana use and the risk of lung and upper aerodigestive tract cancers: results
of a population-based case-control study.
AB - BACKGROUND: Despite several lines of evidence suggesting the biological
plausibility of marijuana being carcinogenic, epidemiologic findings are
inconsistent. We conducted a population-based case-control study of the
association between marijuana use and the risk of lung and upper aerodigestive
tract cancers in Los Angeles. METHODS: Our study included 1,212 incident cancer
cases and 1,040 cancer-free controls matched to cases on age, gender, and
neighborhood. Subjects were interviewed with a standardized questionnaire. The
cumulative use of marijuana was expressed in joint-years, where 1 joint-year is
equivalent to smoking one joint per day for 1 year. RESULTS: Although using
marijuana for > or =30 joint-years was positively associated in the crude
analyses with each cancer type (except pharyngeal cancer), no positive
associations were observed when adjusting for several confounders including
cigarette smoking. The adjusted odds ratio estimate (and 95% confidence limits)
for > or =60 versus 0 joint-years was 1.1 (0.56, 2.1) for oral cancer, 0.84
(0.28, 2.5) for laryngeal cancer, and 0.62 (0.32, 1.2) for lung cancer; the
adjusted odds ratio estimate for > or =30 versus 0 joint-years was 0.57 (0.20,
1.6) for pharyngeal cancer, and 0.53 (0.22, 1.3) for esophageal cancer. No
association was consistently monotonic across exposure categories, and
restriction to subjects who never smoked cigarettes yielded similar findings.
CONCLUSIONS: Our results may have been affected by selection bias or error in
measuring lifetime exposure and confounder histories; but they suggest that the
association of these cancers with marijuana, even long-term or heavy use, is not
strong and may be below practically detectable limits.
PMID- 17035390
TI - Effect of staining procedures on the results of micronucleus assays with
exfoliated oral mucosa cells.
AB - Micronuclei in exfoliated epithelial cells are widely used as biomarkers of
cancer risk in humans. To elucidate the effect of different staining procedures
on the outcome of such investigation, we conducted a study in which the
micronuclei frequencies in oral mucosa cells of heavy smokers (n = 20) and
nonsmokers (n = 10) were evaluated with nonspecific (Giemsa, May-Grunwald-Giemsa)
and DNA-specific (4',6-diamidino-2-phenylindole, Feulgen, acridine orange)
stains, whereas with Giemsa-based stains, the frequencies of micronuclei in
smokers were significantly (4- to 5-fold) higher in the smokers group, no
significant increase was observed with any of the DNA-specific stains.
Furthermore, the evaluation of cells of the two study groups with Feulgen stain
showed that oral mucosa cells from smokers had significantly increased levels of
nuclear anomalies other than micronuclei. These anomalies are consequences of
cell injury found in epithelial cells and are paralleled by formation of keratin
bodies in the cytoplasm that resemble micronuclei. Correlation analyses showed
that micronuclei frequencies scored in Giemsa-stained slides correlated
significantly with karyorrhexis, karyolysis, condensed chromatin, and
binucleates, whereas no such correlations were found with DNA-specific stains.
These findings indicate that nuclear anomalies (and possibly keratin bodies) may
be misinterpreted as micronuclei with nonspecific DNA stains and lead to false
positive results in studies with cells of epithelial origin. Furthermore, our
results show that exposure of oral mucosa cells to genotoxic carcinogens
contained in tobacco smoke does not lead to induction of micronuclei in these
cells.
PMID- 17035392
TI - Influence of patterns of hormone replacement therapy use and mammographic density
on breast cancer detection.
AB - BACKGROUND: There is evidence that factors such as current hormone replacement
therapy (HRT) use and mammographic density may each lower the sensitivity of
mammography and are associated with a greater risk of developing an interval
cancer. This study explores this relationship further by examining the influence
of patterns of HRT use and the percentage of mammographic density on the
detection of breast cancer by classification of interval cancer. METHODS: This
study uses a case-case design nested within a cohort of women screened by the
Ontario Breast Screening Program between 1994 and 2002. Interval cancers, both
those missed at screening but seen on retrospective review (n = 87) or true
intervals without visible tumor signs at screening (n = 288) were matched to 450
screen-detected cancers. The association between the percentage of mammographic
density, measured by radiologists and a computer-assisted method, and HRT use,
ascertained from a mailed questionnaire, and the risk of being diagnosed with an
interval cancer was estimated using conditional logistic regression. RESULTS: A
monotonic gradient of increasing risk for interval cancers was found for each 25%
increase in mammographic density [odds ratio (OR), 1.77; 95% confidence intervals
(95% CI), 1.07-2.95 for missed intervals and OR, 2.16; 95% CI, 1.59-2.94 for true
intervals]. After adjusting for mammographic density, a significantly increased
risk for true-interval cancers remained for women taking estrogen alone (OR,
1.75; 95% CI, 1.11-2.83) as well as for missed- (OR, 2.84; 95% CI, 1.32-6.13) and
true-interval cancers (OR, 1.79; 95% CI, 1.10-2.90) for women taking combined
HRT. CONCLUSIONS: Information on mammographic density and HRT use should
routinely be collected at the time of screening. Women at risk should be made
aware of the lower sensitivity of mammography and offered alternative procedures
for screening.
PMID- 17035391
TI - Racial/ethnic differences in postmenopausal endogenous hormones: the multiethnic
cohort study.
AB - Postmenopausal women with increased estrogens and lowered sex hormone-binding
globulin (SHBG) concentrations are at increased risk of breast cancer. In the
Multiethnic Cohort Study, the highest incidence rates of postmenopausal breast
cancer were observed among Native Hawaiians followed by Japanese Americans,
Whites, African Americans, and Latinas. Ethnic differences in endogenous sex
hormone profiles may contribute to some of the variation in breast cancer
incidence. Plasma concentrations of androstenedione, testosterone, estrone
(E(1)), estradiol (E(2)), and SHBG were measured in 739 postmenopausal women from
the Multiethnic Cohort Study (240 African Americans, 81 Native Hawaiians, 96
Japanese Americans, 231 Latinas, and 91 Whites). After adjusting for age, known
breast cancer risk factors and lifestyle factors, the mean levels of
testosterone, estrogen, and SHBG varied across populations (Ps < or = 0.004).
Across racial/ethnic groups, Native Hawaiians had the highest mean levels of
androstenedione, testosterone, and estrogens and the lowest mean levels of SHBG.
Compared with Whites, Native Hawaiians had higher androstenedione (+22%, P =
0.017), total testosterone (+26%, P = 0.013), bioavailable testosterone (+33%, P
= 0.002), E(1) (> or =21%; P = 0.009), total E(2) (+26%, P = 0.001), bioavailable
E(2) (+31%, P < 0.001), and lower SHBG (-12% P = 0.07) levels. Compared with
Whites, Japanese Americans had higher E(2) (+15%, P = 0.036) and bioavailable
E(2) (+18%, P = 0.024) levels. African Americans also had higher E(1) (+21%, P =
0.004), E(2) (+20%, P = 0.007), and bioavailable E(2) (+20%, P = 0.015) levels
compared with Whites, whereas mean levels in Latinas were similar to those of
Whites. Many of the differences in endogenous postmenopausal hormonal milieu
across these five racial/ethnic groups are consistent with the known differences
in breast cancer incidence across these populations.
PMID- 17035393
TI - General and abdominal obesity and survival among young women with breast cancer.
AB - Among postmenopausal women, obesity is linked to increased risk of breast cancer
and poorer subsequent survival. For premenopausal women, obesity may reduce
incidence, but less is known about its effect on prognosis, particularly for
abdominal obesity. This study investigated whether general or abdominal obesity
at diagnosis influenced survival in a cohort of young women with breast cancer. A
population-based follow-up study was conducted among 1,254 women ages 20 to 54
who were diagnosed with invasive breast cancer between 1990 and 1992 in Atlanta
or New Jersey. Women were interviewed within several months of diagnosis and
asked about their weight and height at age 20 and in the year before diagnosis.
Study personnel did anthropometric measures at the interview. With 8 to 10 years
of follow-up, all-cause mortality status was determined using the National Death
Index (n = 290 deaths). Increased mortality was observed for women who were obese
[body mass index (BMI), > or =30] at the time of interview compared with women of
ideal weight [BMI, 18.5-24.9; stage- and income-adjusted hazard ratio (HR), 1.48;
95% confidence interval (95% CI), 1.09-2.01]. A similar result was seen for the
highest versus lowest quartile of waist-to-hip ratio (HR, 1.52; 95% CI, 1.05
2.19). Strong associations with mortality were found for women who were obese at
age 20 (HR, 2.49; 95% CI, 1.15-5.37) or who were overweight/obese (BMI, > or =25)
at both age 20 and the time of interview (HR, 2.22; 95% CI, 1.45-3.40). This
study provides evidence that breast cancer survival is reduced among younger
women with general or abdominal obesity.
PMID- 17035394
TI - Genetic ancestry and risk factors for breast cancer among Latinas in the San
Francisco Bay Area.
AB - BACKGROUND: Genetic association studies using case-control designs are
susceptible to false-positive and false-negative results if there are differences
in genetic ancestry between cases and controls. We measured genetic ancestry
among Latinas in a population-based case-control study of breast cancer and
tested the association between ancestry and known breast cancer risk factors. We
reasoned that if genetic ancestry is associated with known breast cancer risk
factors, then the results of genetic association studies would be confounded.
METHODS: We used 44 ancestry informative markers to estimate individuals' genetic
ancestry in 563 Latina participants. To test whether ancestry is a predictor of
hormone therapy use, parity, and body mass index (BMI), we used multivariate
logistic regression models to estimate odds ratios (OR) and 95% confidence
intervals (95% CI) associated with a 25% increase in Indigenous American
ancestry, adjusting for age, education, and the participant's and grandparents'
place of birth. RESULTS: Hormone therapy use was significantly less common among
women with higher Indigenous American ancestry (OR, 0.78; 95% CI, 0.63-0.96).
Higher Indigenous American ancestry was also significantly associated with
overweight (BMI, 25-29.9 versus <25) and obesity (BMI, > or =30 versus <25), but
only among foreign-born Latina women (OR, 3.44; 95% CI, 1.97-5.99 and OR, 1.95;
95% CI, 1.24-3.06, respectively). CONCLUSION: Some breast cancer risk factors are
associated with genetic ancestry among Latinas in the San Francisco Bay Area.
Therefore, case-control genetic association studies for breast cancer should
directly measure genetic ancestry to avoid potential confounding.
PMID- 17035395
TI - Increases in plasma carotenoid concentrations in response to a major dietary
change in the women's healthy eating and living study.
AB - BACKGROUND: Cohort studies suggest that higher circulating carotenoid
concentrations through food sources may reduce breast cancer events. Other
intervention studies have not achieved the level of change in circulating
carotenoids required to properly test this hypothesis. METHODS: In a randomized
trial of 2,922 breast cancer survivors, we examined blood and self-reported diet
at baseline and 1 year. Intensive telephone counseling encouraged a plant-based
diet in the intervention group. Diet was measured via 24-hour recalls, and a
panel of plasma carotenoid concentrations was assessed at both time points.
RESULTS: The study intervention was associated with a 51% increase in total
carotenoid concentration, from 2.272 +/- 1.294 to 3.440 +/- 2.320 micromol/L,
achieved mainly by marked increases in targeted carotenoids: alpha-carotene, beta
carotene, and lutein. For each of these targeted carotenoids, the proportion of
the intervention sample remaining below the cutpoint for the lowest baseline
quartile decreased by one third to one half. After 1 year of study, half of the
intervention group was in the highest baseline quartile. No change in
distribution was observed in comparison group. Intervention participants achieved
this change by both dietary pattern and vegetable juice consumption. Participants
who chose to change dietary pattern without consuming significant quantities of
vegetable juice achieved 75% of the level of change observed in other
intervention participants. CONCLUSIONS: Innovative telephone counseling
intervention and dietary targets in the Women's Healthy Eating and Living study
were associated with the level of change in circulating carotenoid concentration
necessary to test the diet and breast cancer hypothesis suggested by cohort
studies.
PMID- 17035396
TI - Measuring perceptions of breast cancer risk.
AB - BACKGROUND: Accurate measurement of people's risk perceptions is important for
numerous bodies of research and in clinical practice, but there is no consensus
about the best measure. OBJECTIVE: This study evaluated three measures of women's
breast cancer risk perception by assessing their psychometric and test
characteristics. DESIGN: A cross-sectional mailed survey to women from a primary
care population asked participants to rate their chance of developing breast
cancer in their lifetime on a 0% to 100% numerical scale and a verbal scale with
five descriptive categories, and to compare their risk to others (seven
categories). Six hundred three of 956 women returned the survey (63.1%), and we
analyzed surveys from the 566 women without a self-reported personal history of
breast or ovarian cancer. RESULTS: Scores on the numeric, verbal, and comparative
measures were correlated with each other (r > 0.50), worry (r > 0.51), the Gail
estimate (r > 0.26), and family history (r > 0.25). The numerical scale had the
strongest correlation with annual mammogram (r = 0.19), and its correlation with
the Gail estimate was unassociated with participants' sociodemographics. The
numerical and comparative measures had the highest sensitivity (0.89-0.90) and
specificity (0.99) for identifying women with very high risk perception. The
numerical and comparative scale also did well in identifying women with very low
risk perception, although the numerical scale had the highest specificity (0.96),
whereas the comparative scale had the highest sensitivity (0.89). CONCLUSION:
Different measures of women's perceptions about breast cancer risk have different
strengths and weaknesses. Although the numerical measure did best overall, the
optimal measure depends on the goals of the measure (i.e., avoidance of false
positives or false negatives).
PMID- 17035397
TI - Comparison of age distribution patterns for different histopathologic types of
breast carcinoma.
AB - BACKGROUND: Historically, female breast carcinoma has been viewed as an
etiologically homogeneous disease associated with rapidly increasing incidence
rates until age 50 years, followed by a slower rate of increase among older
women. More recent studies, however, have shown distinct age incidence patterns
for female breast cancer when stratified by estrogen receptor (ER) expression
and/or histopathologic subtypes, suggesting etiologic heterogeneity. MATERIALS
AND METHODS: To determine if different age incidence patterns reflect etiologic
heterogeneity (more than one breast cancer type within the general breast
carcinoma), we applied "smoothed" age histograms at diagnosis (density plots) and
a two-component statistical mixture model to all breast carcinoma cases (n =
270,124) in the Surveillance, Epidemiology, and End Results Program of the
National Cancer Institute. These overall patterns were then reevaluated according
to histopathologic type, race, and ER expression. RESULTS: A bimodal age
distribution at diagnosis provided a better fit to the data than a single density
for all breast carcinoma populations, except for medullary carcinoma. Medullary
carcinomas showed a single age distribution at diagnosis irrespective of race
and/or ER expression. CONCLUSIONS: Distinct age-specific incidence patterns
reflected bimodal breast cancer populations for breast carcinoma overall as well
as for histopathologic subtypes, race, and ER expression. The one exception was
medullary carcinoma. Of note, medullary carcinomas are rare tumors, which are
associated with germ-line mutations in the BRCA1 gene. These descriptive and
model-based results support emerging molecular data, suggesting two main types of
breast carcinoma in the overall breast cancer population.
PMID- 17035398
TI - The P2X7 receptor: a novel biomarker of uterine epithelial cancers.
AB - OBJECTIVE: To determine expression of the P2X(7) receptor in normal and in cancer
uterine tissues. The rationale was that the receptor P2X(7) regulates
constitutive apoptosis in uterine epithelial cells, and previous studies showed
diminished P2X(7)-mediated apoptosis in cancer uterine cells compared with normal
cells. METHODS: A clinical, experimental feasibility study. Normal (n = 42) and
cancer uterine tissues (n = 47) were obtained from a total of 72 women ages 25 to
75. End points for P2X(7) mRNA were quantitative PCR and in situ hybridization,
and end points for P2X(7) protein were Western blots and immunostaining using
anti-P2X(7) antibody. RESULTS: (a) In normal uteri, P2X(7) mRNA and protein were
expressed predominantly in the epithelial (endometrial, endocervical, and
ectocervical) cells. (b) Expression of the P2X(7) mRNA and protein was absent
from endometrial and endocervical adenocarcinoma tissues and from cervical
squamous cell carcinoma tissues. (c) In cervical dysplasia, P2X(7) protein was
absent in the dysplastic lesions. (d) Semiquantitative analysis using P2X(7) mRNA
(normalized in each tissue to the constitutive glyceraldehyde-3-phosphate
dehydrogenase) and P2X(7) protein levels (normalized in each tissue to the
constitutive tubulin) revealed that P2X(7) mRNA and/or protein levels can
distinguish uterine normal from cancer tissues at high degrees of sensitivity
(92%, 100%) and specificity (100%, 90%). SUMMARY AND CONCLUSIONS: (a) Levels of
the P2X(7) are lower in uterine epithelial cancer tissues than in the
corresponding normal tissues. (b) The data suggest that tissue P2X(7) mRNA and
protein levels could be used as a novel biomarker to differentiate normal and
cancer uterine epithelial tissues.
PMID- 17035399
TI - A phase I-II preoperative biomarker trial of fenretinide in ascitic ovarian
cancer.
AB - PURPOSE: To evaluate study feasibility, toxicity, drug concentrations, and
activity of escalating doses of the synthetic retinoid fenretinide [N-(4
hydroxyphenyl)retinamide (4-HPR)] in ovarian cancer by measuring serum CA125 and
cytomorphometric biomarkers in cancer cells collected from ascitic fluid before
and after treatment. METHODS: Twenty-two naive patients with ascitic ovarian
cancer were treated with escalating doses of 4-HPR at 0, 400, 600, and 800 mg/d
for 1 to 4 weeks before surgery. Changes in the proportion of proliferating cells
expressed by Ki67 and computer-assisted cytomorphometric variables (nuclear area,
DNA index, and chromatin texture) were determined in ascitic cells. Drug levels
were measured by high-performance liquid chromatography. RESULTS: Doses up to 800
mg/d were well tolerated, and no adverse reactions occurred. There was no effect
of 4-HPR on changes in serum CA125, Ki67 expression, which were assessed in 75%
of subjects, and cytomorphometric variables, which were assessed in 80% of
subjects. Plasma retinol levels were significantly lower in affected women than
healthy donors. 4-HPR plasma concentrations increased slightly with increasing
doses and attained a 1.4 micromol/L concentration with 800 mg/d. Drug levels in
malignant ascitic cells and tumor tissue were higher than in plasma but were 50
and 5 times lower, respectively, than in carcinoma cells treated in vitro with 1
micromol/L 4-HPR. CONCLUSIONS: Cell biomarkers can be measured in ascitic cells
to assess drug activity. Under our experimental conditions, 4-HPR did not show
activity in advanced ovarian cancer cells. However, clinical evidence supports
further investigation of fenretinide for ovarian cancer prevention.
PMID- 17035400
TI - Interleukin-1B polymorphisms and gastric cancer risk--a meta-analysis.
AB - Some studies have reported that proinflammatory polymorphisms in interleukin-1B
(IL-1B) and IL-1 receptor antagonist (IL-1RN) genes are associated with increased
gastric cancer risk. However, other studies have shown null or inverse
associations. This meta-analysis reviews and summarizes published evidence for
these associations. Searching the PubMed Database yielded 35 studies that
reported on the association between IL-1B -511 C>T, IL-1B -31 T>C, or IL-1RN
variable number tandem repeat polymorphisms and gastric cancer risk. Q-statistics
and I(2) statistics were calculated to examine heterogeneity. Summary odds ratios
(OR) and 95% confidence intervals (95% CI) were calculated in the random-effects
model using the DerSimonian-Laird method. For all gastric cancers, the overall
ORs (95% CIs) for IL-1B -511 CT versus CC and TT versus CC genotypes were 1.07
(0.91-1.25) and 1.16 (0.95-1.42), respectively. ORs (95% CIs) for the association
between IL-1B -31 CT versus TT and CC versus TT genotypes were 0.99 (0.83-1.19)
and 0.98 (0.78-1.21), respectively. For the associations between IL-1RN and
gastric cancer, ORs (95% CIs) for *2/L versus LL and *2/*2 versus L/L were 1.15
(0.96-1.38) and 1.23 (0.79-1.92). For each of the examined associations, there
was significant heterogeneity among studies; P(heterogeneity) < or = 0.001 and
I(2) ranged from 0.54 to 0.71. Noncardia cancers showed stronger associations
with IL-1B -511 CT or TT and IL1-RN *2/*2 genotypes, but limiting the analysis to
intestinal-type cancers, studies conducted in Western countries, or studies in
which polymorphisms were in Hardy-Weinberg equilibrium, made no material
difference in the results. The overall associations between IL-1B or IL-1RN
proinflammatory polymorphisms and gastric cancer were null but several studies
showed an association. The sources of this variation are unclear.
PMID- 17035401
TI - Influences of chymase and angiotensin I-converting enzyme gene polymorphisms on
gastric cancer risks in Japan.
AB - BACKGROUNDS AND AIMS: The renin-angiotensin system plays an important role in
homeostasis. Angiotensin II, which is generated by chymase and angiotensin I
converting enzyme (ACE), controls blood pressure as well as angiogenesis and cell
proliferation. The aim of this study was to clarify the association of the
chymase gene (CMA/B) and ACE polymorphisms with susceptibility to gastric cancer
and peptic ulcer. METHODS: We assessed CMA/B A/G and ACE insertion/deletion (I/D)
polymorphisms in H. pylori-positive gastric cancers (n = 119), gastric ulcers (n
= 127), and duodenal ulcers (n = 105), and controls (n = 294) consisting of H.
pylori-positive gastritis alone (n = 162) and H. pylori-negative subjects (n =
132) by PCR methods. RESULTS: In CMA/B polymorphism, the age- and sex-adjusted
odds ratios (OR) of A/A and A/G genotypes relative to the G/G genotype for
gastric cancer risk were 7.115 (95% confidence interval, 1.818-27.845) and 1.956
(95% confidence interval, 1.137-3.366), respectively. There was an increased risk
for gastric ulcer in the A/A genotype (OR, 3.450; 1.086-10.960). However, there
was no association between ACE polymorphism and susceptibility to gastric cancer
and peptic ulcer. In allele combination analysis of CMA/B and ACE polymorphisms,
the A/I allele combinations (CMA/B G/A or A/A and ACE I/I genotype) significantly
increased the risk of gastric cancer development (OR, 4.749, 2.050-11.001)
compared with the G/I allele combinations (CMA/B G/G and ACE I/I genotype).
CONCLUSIONS: The CMA/B polymorphism was associated with an increased risk for
gastric cancer and gastric ulcer development. The genotyping test of the renin
angiotensin system could be useful for the screening of individuals with higher
risks of gastric cancer and gastric ulcer.
PMID- 17035403
TI - Cyclin E expression and outcome in pancreatic ductal adenocarcinoma.
AB - The association of high cyclin E expression with poor outcome in some cancers, in
particular breast cancer, suggests that it may play an important role in tumor
biology. Because the influence of cyclin E expression on outcome is yet to be
examined in pancreatic cancer, we assessed the relationship between the
expression of cyclin E, p27(Kip1), and survival in a large cohort of pancreatic
cancer patients with long-term follow-up. Expression of cyclin E and p27(Kip1)
was assessed by immunohistochemistry using tissue microarrays of tumor samples
from 118 patients with pancreatic ductal adenocarcinoma (75 resections and 43
biopsies). High cyclin E expression (>10% positive nuclei) was identified in 39
of 118 (33%) patients. This was associated with poor prognosis on univariate
analysis in the whole cohort (P = 0.005), as well as in the subgroup of 75
patients who underwent operative resection (P = 0.04). On multivariate analysis,
high cyclin E expression was an independent predictor of poor survival in both
the entire cohort (P = 0.005) and the resected subgroup (P = 0.03), and was
superior to all tested clinicopathologic factors (tumor size, lymph node
metastases, differentiation, margin involvement, and perineural invasion) as a
marker of survival. Low p27(Kip1) expression (<5% positive nuclei) was present in
41 of 111 (37%) patients, but was not associated with survival, and coexpression
of p27(Kip1) did not influence the association of high cyclin E expression with
poor survival. High cyclin E expression is a strong independent predictor of poor
outcome in patients with pancreatic cancer. Thus, if these data are confirmed in
independent cohorts, measurement of cyclin E may add significant prognostic
information to the currently used clinicopathologic variables and hence have
potential clinical utility in the management of this disease.
PMID- 17035402
TI - Mutagen sensitivity and neoplastic progression in patients with Barrett's
esophagus: a prospective analysis.
AB - BACKGROUND: Defects in DNA damage recognition and repair have been associated
with a wide variety of cancers. We conducted a prospective study to determine
whether mutagen sensitivity, as determined by an in vitro assay, was associated
with the future development of cancer in patients with Barrett's esophagus, which
is associated with increased risk of progression to esophageal adenocarcinoma.
METHODS: We measured sensitivity to bleomycin in peripheral blood lymphocytes in
a cohort of 220 patients with Barrett's esophagus. We followed these patients for
1,230 person-years (range, 3 months to 10.1 years; median, 6.4 years), using
development of cancer and aneuploidy as end points. A subset of these patients
was evaluated for inactivation of tumor-suppressor genes CDKN2A/p16 and TP53 [by
mutation and loss of heterozygosity (LOH)] in their Barrett's segments at the
time of, or before, the bleomycin test, and the patients were stratified by
CDKN2A/p16 and TP53 status in an analysis of mutagen sensitivity and progression.
RESULTS: Bleomycin-sensitive patients were found to be at significantly greater
risk of developing aneuploidy (adjusted hazard ratio, 3.71; 95% confidence
interval, 1.44-9.53) and nonsignificantly greater risk of cancer (adjusted hazard
ratio, 1.63; 95% confidence interval, 0.71-3.75). Among patients with detectable
LOH at the TP53 locus (on chromosome 17p), increasing bleomycin sensitivity was
associated with increased risk of developing cancer (P(trend) < 0.001) and
aneuploidy (P(trend) = 0.005). CONCLUSIONS: This study supports the hypothesis
that sensitivity to mutagens increases the risk of neoplastic progression in
persons with Barrett's esophagus, particularly those with 17p LOH including TP53.
PMID- 17035404
TI - Evaluation of the 4q32-34 locus in European familial pancreatic cancer.
AB - BACKGROUND: Familial pancreatic cancer (FPC) describes a group of families where
the inheritance of pancreatic cancer is consistent with an autosomal-dominant
mode of inheritance. The 4q32-34 region has been previously identified as a
potential locus for FPC in a large American family. METHODS: The region was
allelotyped in 231 individuals from 77 European families using nine
microsatellite markers, and haplotyping was possible in 191 individuals from 41
families. Families were selected based on at least two affected first-degree
relatives with no other cancer syndromes. RESULTS: Linkage to most of the locus
was excluded based on LOD scores less than -2.0. Eight families were excluded
from linkage to 4q32-34 based on haplotypes not segregating with the disease
compared with a predicted six to seven families. Two groups of families were
identified, which seem to share common alleles within the minimal disease
associated region of 4q32-34, one group with an apparently earlier age of cancer
death than the other pancreatic cancer families. Four genes were identified with
potential tumor suppressor roles within the locus in regions that could not be
excluded based on the LOD score. These were HMGB2, PPID, MORF4, and SPOCK3. DNA
sequence analysis of exons of these genes in affected individuals and in
pancreatic cancer cell lines did not reveal any mutations. CONCLUSION: This locus
is unlikely to harbor a FPC gene in the majority of our European families.
PMID- 17035405
TI - 5,10-Methylenetetrahydrofolate reductase polymorphisms and acute lymphoblastic
leukemia risk: a meta-analysis.
AB - There is evidence supporting a role for 5-10 methylenetetrahydrofolate reductase
(MTHFR) gene variants in acute lymphoblastic leukemia (ALL). To provide a more
robust estimate of the effect of MTHFR polymorphisms on the risk of ALL, we did a
meta-analysis to reevaluate the association between the two most commonly studied
MTHFR polymorphisms (C677T and A1298C) and ALL risk. All case-control studies
investigating an association between the C677T or A1298C polymorphisms and risk
of ALL were included. We applied both fixed-effects and random-effects models to
combine odds ratio (OR) and 95% confidence intervals (95% CI). Q-statistic was
used to evaluate the homogeneity and both Egger and Begg-Mazumdar tests were used
to assess publication bias. The meta-analysis of the C677T polymorphism and risk
of childhood ALL included 13 studies with a total of 4,894 individuals. Under a
fixed-effects model, the TT genotype failed to be associated with a statistically
significant reduction of childhood ALL risk (TT versus CT + CC: OR, 0.88; 95% CI,
0.73-1.06; P = 0.18). However, individuals homozygous for the 677T allele
exhibited a 2.2-fold decrease in risk of adult ALL (TT versus CT + CC: OR, 0.45;
95% CI, 0.26-0.77; P = 0.004). In both cases, no evidence of heterogeneity was
observed. No association between the A1298C variant and susceptibility to both
adult and childhood ALL was disclosed. Our findings support the proposal that the
common genetic C677T polymorphism in the MTHFR contributes to the risk of adult
ALL, but not to the childhood ALL susceptibility.
PMID- 17035406
TI - The risk of cancer following hospitalization for infection in infancy: a
population-based cohort study.
AB - BACKGROUND: The relation between infections in infancy and subsequent cancer risk
in children and young adults is controversial. Our aim was to examine this
association in the Jerusalem Perinatal Study, a population-based cohort
comprising all offspring from western Jerusalem and surroundings born from 1964
to 1976. METHODS: Identity numbers of non-malformed singletons with recorded data
about hospital admission in the 1st year of life (n = 24,554) were linked to the
Population and Cancer Registries. Person-year incidence rates were calculated for
the exposed (admitted for infection) and nonexposed (not admitted for infection)
groups from birth to date of cancer diagnosis, death, or December 31, 2004. We
used Cox proportional hazards models to adjust for covariates associated with
hospitalization. RESULTS: The median follow-up was 36 years. Cancer developed in
283 individuals. Hospitalization for infection was not associated with overall
cancer risk [risk ratio (RR), 0.88; 95% confidence interval (95% CI), 0.56-1.37].
The incidence rate for non-Hodgkin's lymphoma was higher in the exposed compared
with the nonexposed group (RR, 3.46; 95% CI, 1.38-8.68), remaining unchanged
after controlling for birth weight, gender, and maternal education. Leukemia risk
was not significantly associated (RR, 0.44; 95% CI, 0.06-3.24) with
hospitalization for infection. CONCLUSIONS: Hospital admission in the 1st year of
life due to infection is associated with an increased risk of non-Hodgkin's
lymphoma. This is consistent with observations that mild immunodeficiencies
predispose to lymphoma. Survival of infants with subtle immune defects, who may
have previously succumbed to their infection, may contribute to the increased
incidence of non-Hodgkin's lymphoma observed over the last 50 years.
PMID- 17035407
TI - Health status of long-term cancer survivors: results from an Australian
population-based sample.
AB - BACKGROUND: Despite considerable knowledge about the effect of cancer during the
early stages of treatment and survivorship, understanding the longer-term effect
of cancer has only recently become a priority. This study investigated the health
implications of longer-term cancer survivorship in an Australian, population
based sample. METHODS: Using the Australian National Health Survey, 968 longer
term cancer survivors were identified, along with 5,808 age- and sex-matched
respondents without a history of cancer. Four measures of health effect were
compared (quality of life, health status, days out of role, and mental well
being), using polytomous and logistic regression analyses controlling for other
selected chronic conditions. These models were applied across both groups
overall, across groups stratified by presence/absence of cancer, and other
chronic conditions, as well as by tumor site. RESULTS: Compared with matched
respondents without cancer, longer-term cancer survivors reported significant
decrements in health status, days out of role, and mental well-being (all P <
0.02), but not in quality of life. The likelihood of poor health outcomes
(including quality of life) was much higher among survivors who also reported
comorbid chronic conditions. Despite mixed results across tumor site, melanoma
and prostate cancer survivors fared better across most outcomes. CONCLUSIONS:
Clear evidence of excess morbidity among Australian longer-term cancer survivors
seems to be further exacerbated by the presence of comorbid chronic conditions.
Consistent with recent U.S. studies, these results further support the importance
of ongoing surveillance of the growing number of cancer survivors worldwide along
with increased attention to interventions to improve long-term health outcomes.
PMID- 17035408
TI - Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer
prevention trial.
AB - Studies on the relationship between obesity and prostate cancer incidence are
inconsistent. In part, this inconsistency may be due to a differential effect of
obesity on low-grade and high-grade cancer or confounding of the association of
obesity with prostate cancer risk by diabetes. We investigated the associations
of obesity and diabetes with low-grade and high-grade prostate cancer risk. Data
were from 10,258 participants (1,936 prostate cancers) in the Prostate Cancer
Prevention Trial who all had cancer presence or absence determined by prostate
biopsy. Multiple logistic regression was used to model the risk of total prostate
cancer, and polytomous logistic regression was used to model the risk of low
grade and high-grade prostate cancer. Compared with men with body mass index <
25, obese men (body mass index > or =30) had an 18% [odds ratio (OR), 0.82; 95%
confidence interval (95% CI), 0.69-0.98] decreased risk of low-grade prostate
cancer (Gleason <7) and a 29% (OR, 1.29; 95% CI, 1.01-1.67) increased risk of
high-grade prostate cancer (Gleason > or =7) or, alternatively, a 78% (OR, 1.78;
95% CI, 1.10-2.87) increased risk defining high-grade cancer as Gleason sum 8 to
10. Diabetes was associated with a 47% (OR, 0.53; 95% CI, 0.34-0.83) reduced risk
of low-grade prostate cancer and a 28% (OR, 0.72; 95% CI, 0.55-0.94) reduced risk
of high-grade prostate cancer. Associations of obesity or diabetes with cancer
risk were not substantially changed by mutually statistical controlling for each
other. Obesity increases the risk of high-grade but decreases the risk of low
grade prostate cancer, and this relationship is independent of the lower risk for
prostate cancer among men with diabetes.
PMID- 17035409
TI - Perinatal factors and mortality from breast cancer.
AB - Inverse associations have been reported between birthweight and subsequent
mortality from circulatory disease and diabetes among women. In the current
study, we assessed whether perinatal factors were associated with mortality from
breast cancer. This follow-up study consists of breast cancer cases who
participated in two population-based case-control studies of breast cancer in
women under age 45 years conducted between 1983 and 1992 in three western
Washington counties. This analysis is restricted to the 1,024 cases or their
proxies who completed a supplementary questionnaire on perinatal factors from
1994 to 1996. The mean and median length of follow-up among living cohort members
were 153 and 148 months, respectively. Relative to women who were firstborn,
women who were born second or higher in the birth order seemed to have lower
mortality from breast cancer [hazard ratio (HR), 0.2; 95% confidence interval
(95% CI), 0.2-0.3]. In contrast, maternal age of > or =35 years (HR, 1.7; 95% CI,
1.1-2.8) was associated with higher breast cancer mortality relative to a
maternal age of <25 years. Birth order modified the effect of maternal age on
mortality from breast cancer (P = 0.03). There was evidence of increased breast
cancer mortality for birthweight of > or =4,000 g (HR, 1.8; 95% CI, 1.0-3.1) and
twin membership (HR, 2.5; 95% CI, 1.0-6.2). The protective effect of being born
second or higher in the birth order against breast cancer mortality regardless of
maternal age is striking and needs to be confirmed in future studies.
PMID- 17035410
TI - No association between 25-hydroxyvitamin D and mammographic density.
AB - There is increasing evidence that vitamin D may protect against breast cancer.
Some studies have suggested that dietary and supplemental vitamin D is associated
with reduced mammographic density, which is highly associated with breast cancer
risk, although this evidence is not entirely consistent. We investigated a
possible association between circulating 25-hydroxyvitamin D (25OHD), the best
indicator of vitamin D status, and quantitative mammographic density in the
Minnesota Breast Cancer Family Study. Mean values of mammographic density (both
percent and area densities) and circulating levels of 25OHD were compared across
categories of covariates using ANOVA. Models were adjusted for age and body mass
index, as well as other covariates, and also stratified by dietary calcium
intake, menopause, and season. Serum, mammographic density, and questionnaire
data were available from 487 women [133 premenopausal and 354 postmenopausal;
mean age, 56.4 years (range, 27-85 years)] without breast cancer, and for 73%,
the blood was drawn within 1 year of their mammogram. No evidence was found for
an association between 25OHD and either percent density or total dense area.
There was also no evidence for any association when the data were stratified by
season of sample (winter and summer) or menopause. However, both percent density
and dense area were lowest among those in the highest vitamin D quartile with
calcium intake above the median. Unlike some previous reports, vitamin D does not
seem to be related to mammographic density in this cohort.
PMID- 17035411
TI - Haplotype-based association studies of IGFBP1 and IGFBP3 with prostate and breast
cancer risk: the multiethnic cohort.
AB - Collective evidence suggests that the insulin-like growth factor (IGF) system
plays a role in prostate and breast cancer risk. IGF-binding proteins (IGFBP) are
the principal regulatory molecules that modulate IGF-I bioavailability in the
circulation and tissues. To examine whether inherited differences in the IGFBP1
and IGFBP3 genes influence prostate and breast cancer susceptibility, we
conducted two large population-based association studies of African Americans,
Native Hawaiians, Japanese Americans, Latinos, and Whites. To thoroughly assess
the genetic variation across the two loci, we (a) sequenced the IGFBP1 and IGFBP3
exons in 95 aggressive prostate and 95 advanced breast cancer cases to ensure
that we had identified all common missense variants and (b) characterized the
linkage disequilibrium patterns and common haplotypes by genotyping 36 single
nucleotide polymorphisms (SNP) spanning 71 kb across the loci ( approximately 20
kb upstream and approximately 40 kb downstream, respectively) in a panel of 349
control subjects of the five racial/ethnic groups. No new missense SNPs were
found. We identified three regions of strong linkage disequilibrium and selected
a subset of 23 tagging SNPs that could accurately predict both the common IGFBP1
and IGFBP3 haplotypes and the remaining 13 SNPs. We tested the association
between IGFBP1 and IGFBP3 genotypes and haplotypes for their associations with
prostate and breast cancer risk in two large case-control studies nested within
the Multiethnic Cohort [prostate cases/controls = 2,320/2,290; breast cases
(largely postmenopausal)/controls = 1,615/1,962]. We observed no strong
associations between IGFBP1 and IGFBP3 genotypes or haplotypes with either
prostate or breast cancer risk. Our results suggest that common genetic variation
in the IGFBP1 and IGFBP3 genes do not substantially influence prostate and breast
cancer susceptibility.
PMID- 17035412
TI - Fruit and vegetable consumption and incidence of gastric cancer: a prospective
study.
AB - BACKGROUND: Whether fruit and vegetable consumption may confer protection from
gastric cancer remains controversial. METHODS: We prospectively investigated the
association between consumption of fruits and vegetables and the incidence of
gastric cancer among participants from two population-based cohort studies:
36,664 women in the Swedish Mammography Cohort and 45,338 men in the Cohort of
Swedish Men. Participants completed a food-frequency questionnaire in 1997 and
were followed up for cancer incidence through June 2005. Cox proportional hazards
models were used to estimate multivariate hazard ratios (HR) and 95% confidence
intervals (95% CI). RESULTS: During a mean follow-up of 7.2 years, we ascertained
139 incident cases of gastric cancer. Vegetable consumption was inversely
associated with risk of gastric cancer, whereas no significant association was
observed for fruit consumption. After controlling for age and other risk factors,
women and men who consumed > or =2.5 servings/d of vegetables had a HR of 0.56
(95% CI, 0.34-0.93) for developing gastric cancer compared with those who
consumed <1 serving/d. The respective HR for fruit consumption was 0.86 (95% CI,
0.52-1.43). Among specific subgroups of vegetables, consumption of green leafy
vegetables and root vegetables was inversely associated with risk of gastric
cancer; the multivariate HRs comparing > or =3 servings/wk with <0.5 serving/wk
were 0.64 (95% CI, 0.42-0.99) for green leafy vegetables and 0.43 (95% CI, 0.27
0.69) for root vegetables. CONCLUSIONS: Frequent consumption of vegetables may
reduce the risk of gastric cancer.
PMID- 17035413
TI - Death receptor 4 variants and colorectal cancer risk.
AB - The tumor necrosis factor-related apoptosis-inducing ligand receptor modulates
apoptotic response by binding to the proapoptotic death receptor 4 (DR4).
Perturbed apoptosis due to missense alterations in the candidate tumor suppressor
gene DR4 leads to deregulated cell proliferation and cancer predisposition.
Recent studies have discussed the association of DR4 variants with cancer risk.
We evaluated, for the first time, the role of the Thr(209)Arg (626C>G) and
Glu(228)Ala (683A>C) polymorphisms on colorectal cancer risk by genotyping 659
incident cases and 607 healthy controls drawn from the German population-based
Darmkrebs: Chancen der Verhutung durch Screening (DACHS) study. Whereas DR4
Glu(228)Ala was not associated with colorectal cancer, Thr(209)Arg heterozygotes
were at a significantly decreased colorectal cancer risk [odds ratio (OR), 0.73;
95% confidence interval (95% CI), 0.54-0.97]. Stratification according to sex and
age exhibited a significant association of Thr(209)Arg with a decreased risk for
male heterozygotes (OR, 0.68; 95% CI, 0.46-0.99) and for Arg(209) carriers > or
=65 years of age (OR, 0.65; 95% CI, 0.46-0.92) as well as an enhanced risk for
female Ala(228) carriers in a allele dose-dependent manner (P(trend) = 0.01).
Subsite analysis revealed a protective effect of Thr(209)Arg for rectal cancer
risk (OR, 0.67; 95% CI, 0.48-0.95) and a significant risk increase for Ala(228)
carriers with advanced colorectal cancer stages (P(trend) = 0.04). Haplotype
analysis revealed a 2.4-fold risk for carriers of the rare 626C-683C haplotype
(1% prevalence in the general population; OR, 2.37; 95% CI, 0.98-5.76). The score
statistic yielded an empirical P of 0.03 of the haplotype-specific test for 626C
683C based on 20,000 simulations, suggesting that DR4 626C-683C may affect
colorectal cancer predisposition.
PMID- 17035414
TI - Total magnesium intake and colorectal cancer incidence in women.
PMID- 17035415
TI - No association between serum insulin-like growth factor (IGF)-I, IGF-binding
protein-3, and lung cancer risk.
PMID- 17035416
TI - Maternal androgen and estrogen concentrations are not associated with blood
pressure changes in uncomplicated pregnancies.
AB - Systolic blood pressure increase between the second and third trimester of
pregnancy has been associated with a substantially reduced maternal breast cancer
risk, and it has been suggested that elevated androgens mediate the association.
Androgen and estrogen concentrations were measured in maternal serum collected in
86 uncomplicated, singleton pregnancies. Overall, there were no consistent or
statistically significant patterns of association between the hormones and
systolic, diastolic, or mean arterial blood pressure or blood pressure change
between trimesters. Results were similar with adjustment for factors related to
the hormones. These data are not consistent with the hypothesis that elevated
androgen concentrations mediate the observed reduction in maternal breast cancer
risk associated with increases in blood pressure over the pregnancy.
PMID- 17035417
TI - "Vital" sign?
PMID- 17035418
TI - Pulmonary hypertension trials: current end points are flawed, but what are the
alternatives?
PMID- 17035419
TI - Lung cancer: family history matters.
PMID- 17035420
TI - Did Lady Windermere have cystic fibrosis?
PMID- 17035421
TI - Optimal therapy for methicillin-resistant Staphylococcus aureus pneumonia: what
is the best dosing regimen?
PMID- 17035422
TI - Emergency department hypotension predicts sudden unexpected in-hospital
mortality: a prospective cohort study.
AB - OBJECTIVE: The prevalence and prognostic significance of nontraumatic hypotension
measured in the emergency department (ED) have not been studied. We hypothesized
that ED hypotension confers risk of in-hospital mortality. DESIGN: Prospective
cohort study. SETTING: Large urban ED with 115,000 visits per year. PARTICIPANTS:
Nontrauma ED patients aged > 17 years admitted to the hospital were prospectively
identified on a random sample of 24-h blocks during 2004 to 2005. "Exposures" had
any systolic BP (SBP) < 100 mm Hg in the ED; "nonexposures" all had SBP >/= 100
mm Hg in the ED. Deaths were classified as sudden and unexpected by independent
observers using explicit criteria. OUTCOME MEASURES: Mortality rates were
compared with confidence intervals (CIs), Kaplan-Meier survival curves, and
multivariate logistic regression. RESULTS: A total of 4,790 patients were
enrolled during the study period, with 887 patients (19%) in the exposure group.
Exposures were more likely to die in the hospital compared with nonexposures (8%
vs 3%; 95% CI for difference of 5%, 4 to 8%). Exposures were more likely to have
sudden and unexpected death compared with nonexposures (2% vs 0.2%, 95% CI for
difference of 1.8%, 1 to 3%). Kaplan-Meier estimates showed increased mortality
in the exposure group at all time points (log-rank test, p < 0.001). Multivariate
logistic regression revealed exposure to hypotension as an independent predictor
of in-hospital mortality (odds ratio, 2.0; 95% CI, 1.3 to 2.8). CONCLUSION:
Nontraumatic hypotension was documented in 19% of a random sample of ED patients
admitted to the hospital. Patients exposed to hypotension had a significantly
increased risk of death during hospitalization.
PMID- 17035423
TI - Predictors of mortality for methicillin-resistant Staphylococcus aureus health
care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic
indices.
AB - OBJECTIVE: The goal of this investigation was to determine whether vancomycin
pharmacokinetic indexes (eg, serum trough concentrations or area under the
concentration curve [AUC] values) were associated with mortality for patients
with health-care-associated pneumonia (HCAP) attributed to methicillin-resistant
Staphylococcus aureus (MRSA). DESIGN: A retrospective, single-center,
observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban
teaching facility. PATIENTS: Adult patients requiring hospitalization who were
identified as having HCAP attributed to MRSA by BAL semi-quantitative cultures.
INTERVENTIONS: Retrospective data collection from automated hospital,
microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: One hundred
two patients with MRSA HCAP were identified over a 6.5-year period. Thirty-two
patients (31.4%) died during their hospitalization. The mean (+/- SD) vancomycin
trough concentrations (13.6 +/- 5.9 vs 13.9 +/- 6.7 microg/mL, respectively; p =
0.866) and AUC values (351 +/- 143 vs 354 +/- 109 microg/h/mL, respectively; p =
0.941) did not differ between survivors and nonsurvivors. The stratification of
the vancomycin trough concentrations and AUC values yielded no relationship with
hospital mortality. CONCLUSIONS: We found no evidence that greater vancomycin
trough concentrations or AUC values correlated with hospital outcome. Based on
these results, aggressive dosing strategies for vancomycin (eg, trough
concentrations of > 15 microg/mL) may not offer any advantage over traditional
dose targets (range, 5 to 15 microg/mL).
PMID- 17035424
TI - Agreement between quantitative cultures of postintubation tracheal aspiration and
plugged telescoping catheter, protected specimen brush, or BAL for the diagnosis
of nosocomial pneumonia.
AB - BACKGROUND: The diagnosis of ventilator-associated pneumonia relies on protected
specimen brush (PSB), BAL, and plugged telescoping catheter (PTC) procedures. In
the particular setting of nosocomial pneumonia (NP) occurring in non-mechanically
ventilated patients, no consensus exists on their use. When mechanical
ventilation (MV) becomes mandatory, postintubation tracheal aspiration (PITA)
could be a simple, fast, and cheap diagnostic tool. Our aim was to compare the
diagnostic accuracy of PITA to that of PSB, BAL, or PTC in patients requiring MV
for suspected NP. METHODS: Patients with a prior hospital stay of > or = 48 h who
required MV for suspicion of NP were prospectively enrolled in the study. PITA
was performed by sterile suction. Within 2 h, pulmonary samples were obtained by
PSB, BAL, or blinded PTC, which are referred to hereafter as "reference methods"
(RMs). The definite diagnosis of NP was made using a composite item of clinical,
radiologic, and bacteriologic (ie, blood or pleural fluid cultures) patterns. The
agreement between the quantitative microbiological results obtained with PITA and
those of the RMs was assessed by the kappa-statistic. The sensitivity,
specificity, and positive and negative likelihood ratios of PITA and RMs were
calculated taking the definite diagnosis of NP as the reference. RESULTS: There
were 44 cases (63.8%) of confirmed NP. The kappa-statistic was 0.71. The
sensitivity, specificity, and positive and negative likelihood ratios were 77%,
84%, 4.80, and 0.27, respectively, for PITA, and 75%, 88%, 6.25, and 0.28,
respectively, for RMs. CONCLUSIONS: PITA may be a reliable alternative to RMs in
the particular setting of NP in newly mechanically ventilated patients.
PMID- 17035425
TI - Hyperchloremic acidosis increases circulating inflammatory molecules in
experimental sepsis.
AB - RATIONALE: Hyperchloremic acidosis is common in the critically ill and is often
iatrogenic. We have previously shown that hyperchloremic acidosis increases
nuclear factor-kappaB DNA binding in lipopolysaccharide-stimulated RAW 264.7
cells. However, evidence that hyperchloremic acidosis leads to increased
inflammation in vivo has been limited to nitric oxide. OBJECTIVES: To determine
if acidosis, induced by dilute hydrochloric acid (HCl) infusion, will increase
circulating inflammatory mediator levels in an experimental model of severe
sepsis in rats. METHODS: Eighteen hours after inducing lethal sepsis by cecal
ligation and puncture in 20 adult, male, Sprague-Dawley rats, we randomized
animals into three groups. In groups 2 and 3, we began an IV infusion of 0.1 N
HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15 mEq/L,
respectively. In group 1, we infused a similar volume of lactated Ringer
solution. In all groups infusion continued 8 h or until the animal died.
MEASUREMENTS AND MAIN RESULTS: We measured arterial blood gases, whole-blood
lactate, and chloride, tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10
levels at 0 h, 4 h, and 8 h. All measured cytokines increased over time. Compared
to group 1, animals in groups 2 and 3 exhibited greater increase in all three
cytokines, with the greatest increases seen with severe acidosis. CONCLUSION:
Moderate (SBE, - 5 to - 10) and severe (SBE, - 10 to - 15) acidosis, induced by
HCl infusion, increases circulating levels of IL-6, IL-10, and TNF in
normotensive septic rats.
PMID- 17035426
TI - Association between lung cancer incidence and family history of lung cancer: data
from a large-scale population-based cohort study, the JPHC study.
AB - STUDY OBJECTIVES: To clarify the possibility of a hereditary predisposition to
lung cancer, we investigated the association between a family history of lung
cancer and subsequent risk of lung cancer in a large-scale, population-based
cohort study. DESIGN: We investigated 102,255 middle-aged and older Japanese
subjects (48,834 men and 53,421 women) with 13-year follow-up. A total of 791
cases of lung cancer were newly diagnosed during the follow-up period. RESULTS: A
family history of lung cancer in a first-degree relative was associated with a
significantly increased risk of lung cancer (hazard ratio [HR], 1.95; 95%
confidence interval [CI], 1.31 to 2.88). The association was stronger in women
than in men (HR, 2.65; 95% CI, 1.40 to 5.01 and HR, 1.69; 95% CI, 1.03 to 2.78,
respectively), and in never-smokers than in current smokers (HR, 2.48; 95% CI,
1.27 to 4.84 and HR, 1.73; 95% CI, 0.99 to 3.00, respectively). In addition,
family history was more strongly associated with the risk of squamous cell
carcinoma than with other histologic types (HR, 2.79; 95% CI, 1.37 to 5.68),
while no clear increase in risk was observed in adenocarcinoma and small cell
carcinoma. A family history of overall cancer was not associated with an
increased risk of lung cancer. CONCLUSIONS: These results suggest that those with
a family history of lung cancer are more likely to acquire lung cancer
themselves.
PMID- 17035427
TI - Unique characteristics of systemic sclerosis sine scleroderma-associated
interstitial lung disease.
AB - STUDY OBJECTIVES: To describe the characteristics of systemic sclerosis sine
scleroderma (ssSSc)-associated interstitial lung disease (ILD) presenting as
idiopathic interstitial pneumonia (IIP). DESIGN: Retrospective review of six
patients with ssSSc-associated ILD diagnosed after referral for evaluation of
IIP. MEASUREMENT AND RESULTS: All patients were white, their mean age was 56
years (range, 37 to 86), and gender was evenly divided. Sclerodactyly, skin
thickening, and digital edema were absent in all patients. All patients had
scattered telangiectasia, and four patients had Raynaud phenomenon with abnormal
nailfold capillaroscopy findings. All described gastroesophageal reflux, and
three patients had esophageal dysmotility by esophagography. All had restrictive
pulmonary physiology and a reduced diffusion capacity. High-resolution CT
revealed nonspecific interstitial pneumonia (NSIP) or usual interstitial
pneumonia (UIP) radiographic patterns. Of the three patients who underwent
surgical lung biopsy, two patients had NSIP and one patient had UIP pathologic
patterns. Five patients had asymptomatic pericardial effusions and elevated
pulmonary artery pressures by echocardiography. All patients had nucleolar
staining anti-nuclear antibodies (ANAs), and one patient was anti-Scl-70
positive. All five anti-Scl-70-negative patients were anti-Th/To positive, and
the anti-Scl-70-positive patient was anti-Th/To negative. CONCLUSIONS: In the
presentation of an IIP, the presence of a nucleolar-staining ANA, telangiectasia,
Raynaud phenomenon with abnormal capillaroscopy findings, gastroesophageal
reflux, or pericardial disease suggests underlying systemic sclerosis. These
findings should aid clinicians in the evaluation and treatment of patients with
otherwise undefined ILD.
PMID- 17035428
TI - Different angiogenic activity in pulmonary sarcoidosis and idiopathic pulmonary
fibrosis.
AB - BACKGROUND: Recent evidence has shown that several chemokines--including those
involved in angiogenesis--have been implicated in the pathogenesis of idiopathic
pulmonary fibrosis (IPF) and sarcoidosis. We speculated that these differences
could be attributed to distinct angiogenic and angiostatic profiles. This
hypothesis was investigated by estimating the levels of three angiogenic
chemokines (growth-related gene [GRO]-alpha, epithelial neutrophil-activating
protein [ENA]-78, and interleukin [IL]-8), and three angiostatic chemokines
(monokine induced by interferon (IFN)-gamma [MIG], IFN-gamma-inducible protein
[IP]-10, and IFN-gamma-inducible T-cell alpha chemoattractant) in serum and BAL
fluid (BALF). METHODS: We studied prospectively 20 patients with sarcoidosis
(median age, 46 years; range, 25 to 65 years), 20 patients with IPF (median age,
68 years; range, 40 to 75 years), and 10 normal subjects (median age, 39 years;
range, 26 to 60 years). RESULTS: The GRO-a serum and BALF levels of IPF patients
were found significantly increased in comparison with healthy subjects (799 pg/mL
vs 294 pg/mL [p = 0.022] and 1,827 pg/mL vs 94 pg/mL [p < 0.001], respectively)
and sarcoidosis patients (799 pg/mL vs 44 pg/mL [p < 0.001] and 1,827 pg/mL vs
214 pg/mL [p < 0.001], respectively). Moreover, ENA-78 and IL-8 BALF levels in
IPF patients were significantly higher compared with sarcoidosis patients (191
pg/mL vs 30 pg/mL [p < 0.001] and 640 pg/mL vs 94 pg/mL [p = 0.03],
respectively). MIG serum levels in IPF patients were found significantly
upregulated in comparison with sarcoidosis patients and healthy control subjects.
However, MIG and IP-10 BALF levels (1,136 pg/mL vs 66 pg/mL [p < 0.001] and 112
pg/mL vs 56 pg/mL [p = 0.037], respectively) were significantly higher in
sarcoidosis patients compared with IPF patients. CONCLUSIONS: Our data suggest
distinct angiogenic profiles between IPF and sarcoidosis, indicating a potential
different role of CXC chemokines in the local immunologic response in IPF and
pulmonary sarcoidosis.
PMID- 17035429
TI - Fatigue is associated with quality of life in sarcoidosis patients.
AB - BACKGROUND: Fatigue is one of the core symptoms of sarcoidosis patients. Although
it is known that fatigue affects quality of life (QOL) in other patient groups,
this relationship has never been studied in sarcoidosis patients using a reliable
and valid fatigue scale and a multidimensional QOL instrument. The present cross
sectional study among sarcoidosis patients attempts to gain more insight into
this relationship. METHODS: One hundred forty-five sarcoidosis patients of an
outpatient pulmonary clinic in Zagreb, Croatia, completed the Fatigue Assessment
Scale (FAS) and QOL scale (World Health Organization Quality of Life Assessment
Instrument-100) between January 2002 and May 2004. Clinical parameters were
derived from the patients' medical files. RESULTS: Tired patients reported a
worse QOL in all domains and fatigue negatively predicted all QOL domains by
means of multivariate regression analyses (beta values ranging from - 0.31 to -
0.64, all p < 0.001). Corticosteroid use was not a predictor of QOL. Diffusion
capacity of the lung for carbon monoxide was the only clinical parameter
associated with a QOL domain, namely level of independence. CONCLUSIONS: Fatigue
was related to all QOL domains. Furthermore, standard clinical parameters were
not associated with fatigue or QOL, except for level of independence. If these
results were to be replicated in a prospective study, fatigue as measured by the
FAS could be a good indicator of QOL in sarcoidosis patients.
PMID- 17035430
TI - Prospective analysis of cystic fibrosis transmembrane regulator mutations in
adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection.
AB - BACKGROUND: Bronchiectasis and pulmonary infection with nontuberculous
mycobacteria (NTM) may be associated with disease-causing mutations in the cystic
fibrosis transmembrane regulator (CFTR). METHODS: Fifty adult patients at
Stanford University Medical Center with a diagnosis of bronchiectasis and/or
pulmonary NTM infection were prospectively characterized by sweat chloride
measurement, comprehensive mutational analysis of CFTR, and sputum culture
results. RESULTS: A de novo diagnosis of cystic fibrosis (CF) was established in
10 patients (20%). Patients with CF were more likely than those without CF to
have mucus plugging seen on chest high-resolution CT, and women with a CF
diagnosis were thinner, with a significantly lower mean body mass index than the
non-CF subjects. Thirty CFTR mutations were identified in 24 patients (50%
prevalence). Sweat chloride concentration was elevated > 60 mEq/dL (diagnostic of
CF) in seven patients (14%), and from 40 to 60 mEq/dL in eight patients (16%).
The frequency of CFTR mutations was elevated above that expected in the general
population: heterozygous DeltaF508 (12% vs 3%), R75Q (14% vs 1%), and intron 8 5T
(17% vs 5 to 10%). Other known CFTR mutations identified were V456A, G542X,
R668C, I1027T, D1152, R1162L, W1282X, and L183I. Three novel CFTR mutations were
identified: A394V, F650L, and C1344S. CONCLUSIONS: Mutations in CFTR that alter
RNA splicing and/or functional chloride conductance are common in this
population, and are likely to contribute to the susceptibility and pathogenesis
of adult bronchiectasis and pulmonary NTM infection. Careful clinical evaluation
for disease cause should be undertaken in this clinical context.
PMID- 17035431
TI - The effect of 1 week of continuous positive airway pressure treatment in
obstructive sleep apnea patients with concomitant gastroesophageal reflux.
AB - STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) have a very high
incidence of gastroesophageal reflux (GER). Previous studies have shown that the
use of continuous positive airway pressure (CPAP) reduces the frequency of reflux
events, but these studies only assessed the effect of a single night of
treatment. The aim of this study was to assess the effect of 1 week of CPAP
treatment on reflux in patients with OSA and GER. DESIGN: Sixteen patients with
OSA and GER were recruited. Polysomnography followed by 24-h, continuous
esophageal pH monitoring were performed at baseline. Patients with an apnea
hypopnea index (AHI) > 20/h and 24-h acid contact time (ACT) of at least 6% were
included. As part of the polysomnography-qualifying evaluation, all patients
underwent CPAP titration to reduce the AHI to < 10/h. Patients were then sent
home receiving nasal CPAP for 1 week; after 1 week, esophageal pH monitoring was
repeated while receiving CPAP. MEASUREMENTS AND RESULTS: The AHI fell from 63.3
+/- 38.5 to 3.2 +/- 2.2/h (mean +/- SD) [p < 0.001]. Total ACT fell from 13.9 +/-
11.6 to 5.6 +/- 2.7% (p < 0.001). The upright ACT was reduced from 12.4 +/- 6.8
to 6.8 +/- 3.8% (p = 0.01), and the supine (during the sleeping interval) ACT was
reduced from 16.3 +/- 18.8 to 3.8 +/- 7.6% (p < 0.01). Eighty-one percent of the
patients had a reduction in supine ACT to within the normal range (< 4%).
CONCLUSIONS: In OSA patients with significant heartburn complaints, CPAP would
appear to be an efficacious approach to the treatment of both disorders.
PMID- 17035432
TI - Twenty-four-hour ambulatory BP in snoring children with obstructive sleep apnea
syndrome.
AB - INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a known risk factor for
hypertension in adults. This relationship is less clear in childhood OSAS.
OBJECTIVE: This study examined the relationship between OSAS and 24-h ambulatory
BP (ABP), a more accurate assessment than casual BP, in children with snoring.
METHODS: Snoring children aged 6 to 15 years who underwent polysomnography in the
sleep laboratory were recruited. MEASUREMENT: Twenty-four-hour ABP monitoring was
initiated a few hours before polysomnography. The children were classified into
two groups: a high apnea-hypopnea index (AHI) group (obstructive AHI > 5/h), and
a low-AHI group (AHI < or = 5/h). Mean sleep, wake, and 24-h systolic BP (SBP)
and diastolic BP (DBP) were recorded. A child was considered a "nondipper" if his
or her mean SBP and DBP did not decrease by >/= 10% during sleep. RESULTS: Ninety
six children (mean age +/- SD, 9.4 +/- 2.8 years) were recruited. Forty-one
children were obese. When awake, the high-AHI group children had a significantly
higher SBP. When asleep, both SBP and DBP were higher in the high-AHI group. Age,
body mass index (BMI) z score, and desaturation index (DI) were significant
predictors for elevated sleep DBP. BMI z score was the only significant predictor
for wake and sleep SBP. Sixteen children (17%) had hypertension, and all were
nondippers. Obese children in the high-AHI group had a significantly higher
prevalence of hypertension than obese children in the low-AHI group. This
relationship was not found in nonobese children. CONCLUSION: The current study
shows that increased DI contributed to the elevation of sleep DBP elevation.
PMID- 17035433
TI - Pressure-relief continuous positive airway pressure vs constant continuous
positive airway pressure: a comparison of efficacy and compliance.
AB - OBJECTIVES: To compare polysomnographic data and compliance in sleep apnea
patients receiving continuous positive airway pressure (CPAP) and pressure-relief
CPAP (PRCPAP) [C-flex; Respironics; Murrysville, PA] as first treatment in the
sleep laboratory and subsequently at home. DESIGN: A prospective, randomized,
crossover design was used in the sleep laboratory, and a prospective randomized
design was used at home. PATIENTS: Data were collected from 52 sleep apnea
patients for whom CPAP was used for the first time. INTERVENTIONS: Treatment with
constant CPAP and PRCPAP. MEASUREMENTS AND RESULTS: Patients with a first-time
diagnosis of obstructive sleep apnea syndrome (OSAS) underwent conventional CPAP
titration. Thereafter, polysomnography was performed at the titrated pressure
using both the fixed CPAP pressure mode and the PRCPAP mode in a randomized
crossover approach. The patients were then discharged home for 7 weeks of
treatment with the last-applied treatment mode, and compliance data were
established at the end of that time. The average apnea-hypopnea index was 53.3/h
in the "diagnostic night," 5.8/h with CPAP, and 7.0/h with PRCPAP. The native
arousal index was 35.2/h, 12.6/h with CPAP, and 12.9/h with PRCPAP (not
significant [NS]). The central apnea index was 0.7/h with CPAP and 1.2/h with
PRCPAP (p < 0.05). Compliance after 7 weeks was, on average, 9.4 min longer with
PRCPAP than with CPAP (NS). Evaluation of a 13-item questionnaire showed scores
of 16.4 for PRCPAP and 18.1 for constant CPAP (NS) [the fewer the complaints, the
lower the score]. With regard to oral dryness, the score with PRCPAP (1.4) was
significantly lower than with constant CPAP (1.9) [p < 0.05]. This difference was
no longer detectable after 7 weeks. CONCLUSION: In terms of the effectiveness in
treating obstructive sleep apnea, PRCPAP and constant CPAP are comparable. During
the first night of treatment, patients receiving PRCPAP had less dryness of
mouth; over a period of 7 weeks, this difference disappeared. Nightly use of the
device was comparable in both groups. PRCPAP is therefore a new ventilation mode
that enables effective treatment of OSAS patients. Further studies should be done
to investigate the effects of expiratory pressure lowering in low-compliance
patients and patients requiring CPAP > 9 cm H(2)O or experiencing dry mouth with
CPAP.
PMID- 17035434
TI - Abnormalities of the bronchial arteries in asthma.
AB - STUDY OBJECTIVES: The bronchial arteries supply systemic blood to the airways,
tracheobronchial lymph nodes, and nerves. Their structure has not been studied in
patients with asthma. DESIGN: Case-control study of pathologic changes of
bronchial arteries in asthma. PARTICIPANTS AND METHODS: Postmortem lungs were
examined from three case groups: (1) fatal asthma (n = 12), death due to asthma;
(2) nonfatal asthma (n = 12), asthmatic and death due to nonrespiratory causes;
and (3) nonasthmatic control subjects (n = 12), no history of asthma and death
due to nonrespiratory causes. In bronchial arteries with outer diameters of 0.1
to 1.0 mm, the areas of lumen, intima, and media were measured and compared
between case groups. RESULTS: There were no significant differences in artery
size (outer diameter) or in medial area between the three groups. In the two
asthma groups, the intimal area was increased (p < 0.05), with a corresponding
decrease in luminal area compared with the control group. There was a significant
effect of gender, age, and smoking on intimal area. In the asthma cases, the area
of bronchial artery intima was related to duration of asthma (p < 0.05), and this
increase was associated with smooth muscle proliferation, reduplication, and
calcification of the elastica, but not with inflammatory cell infiltration.
CONCLUSIONS: While the pathophysiologic significance of these changes is
uncertain, the relation to duration of asthma, age, and smoking suggests a
secondary response to chronic airway disease.
PMID- 17035435
TI - Depressive symptoms and adherence to asthma therapy after hospital discharge.
AB - STUDY OBJECTIVES: To evaluate the effect of depressive symptoms on adherence to
therapy after discharge in patients hospitalized for asthma exacerbations.
DESIGN: Prospective cohort study in which depressive symptoms were assessed
during hospitalization and use of asthma medications was electronically monitored
for 2 weeks after discharge. SETTING: Inner-city academic hospital in Baltimore,
MD. PATIENTS: Patients were 59 adults with a mean age of 43.2 +/- 10.9 years (+/-
SD), who were mostly female (64%), African American (80%), and were hospitalized
for an asthma exacerbation. MEASUREMENT AND RESULTS: Depressive symptoms were
assessed with the Center for Epidemiological Studies-Depression scale. Electronic
monitors were used to evaluate inhaled corticosteroid and oral corticosteroid use
for up to 2 weeks after discharge. Forty-one percent of patients had high levels
of depressive symptoms. Mean adherence to therapy was significantly lower in
patients with (vs without) high levels of depressive symptoms (60 +/- 26% vs 74
+/- 21%, p + 0.02). Even after controlling for age, gender, and education,
depressive symptoms were a significant and independent predictor of poorer
adherence. High levels of depressive symptoms were associated with a 11.4-fold
increase (95% confidence interval, 2.2 to 58.2) in the odds of poor adherence to
therapy after adjustment for potential confounders. CONCLUSIONS: Depressive
symptoms are common in inner-city adults hospitalized for asthma exacerbations
and identify a subset of patients at high risk for poor adherence to asthma
therapy after discharge. Further research is needed to determine if screening for
and treating depression improves adherence and asthma outcomes in this
population.
PMID- 17035436
TI - What is worse for asthma control and quality of life: depressive disorders,
anxiety disorders, or both?
AB - BACKGROUND: The high burden of asthma appears to be related to poor asthma
control. Although previous studies have reported associations between depressive
disorders (DDs) and anxiety disorders (ADs) and worse asthma control and quality
of life, the relative impact of these disorders on asthma control and quality of
life has not been explored. This study evaluated the relative impact of having a
DD and/or AD on asthma control and quality of life. METHOD: Five hundred four
consecutive adults with confirmed, physician-diagnosed asthma underwent a brief,
structured psychiatric interview using the Primary Care Evaluation of Mental
Disorders. Asthma control and asthma-related quality of life were assessed using
the Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life
Questionnaire (AQLQ). All patients underwent standard spirometry. RESULTS: Thirty
one percent of patients (n = 157) met the diagnostic criteria for one or more
psychiatric disorders (8% had DD only, 12% had AD only, and 11% had both).
Analyses revealed independent effects for DDs on total ACQ scores (p < 0.01), and
for DDs and ADs on total AQLQ scores and all four AQLQ subscales (p < 0.05).
There were no interaction effects. CONCLUSIONS: Results suggest that DDs and ADs
are associated with worse asthma-related quality of life, but only DDs are
associated with worse asthma control. Interestingly, having both a DD and an AD
did not confer additional risk for worse asthma control or quality of life.
Physicians may want to consider the differential impact of negative mood states
when assessing levels of asthma control and quality of life.
PMID- 17035437
TI - Increase in concentration of soluble CD86 after segmental allergen challenge in
patients with allergic asthma.
AB - STUDY OBJECTIVE: To investigate the effects of segmental allergen challenge on
the concentration of soluble CD86 (sCD86) in BAL fluids in patients with allergic
asthma. METHODS: BAL fluid and peripheral blood were collected at baseline, 24 h
after segmental saline solution or allergen challenge by fiberoptic bronchoscopy
and venepuncture, respectively, from 10 patients with allergic asthma. Total and
differential cell counts in BAL fluid were performed, and sCD86 levels in both
BAL fluid and serum were measured by enzyme-linked immunosorbent assay. RESULTS:
In allergic asthmatics, there was no significant increase in BAL sCD86
concentrations after saline solution challenge (median, 2.0 IU/L; 25th to 75th
percentiles, 0 to 3.4) compared with baseline control subjects (median, 1.2 IU/L;
25th to 75th percentiles, 0 to 3.6 IU/mL; p = 0.735); however, sCD86
concentrations were significantly elevated after allergen challenge (median, 8.1
IU/L; 25th to 75th percentiles, 4.4 to 17.0 IU/mL; p < 0.001). The concentrations
of sCD86 in BAL fluid after allergen challenge exceeded levels that could be
accounted for passive transudation from the circulation, based on the magnitude
of increases in BAL albumin concentrations. CONCLUSIONS: These data indicate that
allergen challenge results in a significant local accumulation of sCD86 within
the airways, and that the local release of sCD86 may play a role in allergen
induced inflammatory processes in the asthmatic airways.
PMID- 17035438
TI - Evaluation of asthma with hyperpolarized helium-3 MRI: correlation with clinical
severity and spirometry.
AB - BACKGROUND: Accurate characterization of asthma severity is difficult due to the
variability of symptoms. Hyperpolarized helium-3 MRI (H(3)HeMR) is a new
technique in which the airspaces are visualized, depicting regions with airflow
obstruction as "ventilation defects." The objective of this study was to compare
the extent of H(3)HeMR ventilation defects with measures of asthma severity and
spirometry. METHODS: Patients with a physician diagnosis of asthma and normal
control subjects underwent H(3)HeMR. For each person, the number and size of
ventilation defects were scored and the average number of ventilation defects per
slice (VDS) was calculated. The correlations of the imaging findings with
measures of asthma severity and spirometry were determined. RESULTS: There were
58 patients with asthma (mild-intermittent, n = 13; mild-persistent, n = 13;
moderate-persistent, n = 20; and severe-persistent, n = 12) and 18 control
subjects. Mean +/- SE VDS for asthmatics was significantly greater than for
control subjects (0.99 +/- 0.15 vs 0.26 +/- 0.22, p = 0.004). Among asthmatics,
VDS was significantly higher for the group with moderate-persistent and severe
persistent disease than for the group with mild-intermittent and mild-persistent
disease (1.37 +/- 0.24 vs 0.53 +/- 0.12, p < 0.001). VDS correlated significantly
with FEV(1)/FVC (r = - 0.51, p = 0.002), forced expiratory flow between 25% and
75% from the beginning of FVC (FEF(25-75%)) percentage of predicted for height,
sex, and race (%predicted) [r = - 0.50, p = 0.001], and FEV(1) %predicted (r = -
0.40, p = 0.002), but not with FVC %predicted (r = - 0.26, p = 0.057) and peak
expiratory flow %predicted (r = - 0.16, p = 0.231). Many asthmatics had an
elevated VDS, but their spirometric indexes, except FEF(25%-75%), were normal.
Most ventilation defects were < 3 cm in size for all asthmatics. In the group of
patients with moderate-to-severe persistent asthma, there were more defects > or
=3 cm than in the group with mild-intermittent and mild-persistent disease (p =
0.021). CONCLUSIONS: Regional changes of airflow obstruction in asthmatics
depicted by H(3)HeMR correlate with measures of asthma severity and spirometry.
PMID- 17035439
TI - Room air entrainment during beta-agonist delivery with heliox.
AB - Studies of the efficacy of heliox in patients with severe asthma have shown mixed
results. Among the factors that are responsible for variable outcomes, the
failure of heliox delivery systems to prevent room air entrainment (RAE) during
beta-agonist delivery is probably the most critical. While keeping the rotameter
flow rate (FR) of heliox mixed 70:30 to a nebulizer at 10 L/min, the FR of heliox
from a second gas source to a T-connector (TC) was increased during the delivery
of the beta-agonist with a conventional T-nebulizer delivery system (TNDS). A
negative peak inspiratory flow (pneumotachometer reading) or a helium
concentration of < 70% (quadralizer reading) were indicators of RAE. RAE was
tested during spontaneous tidal breathing and acute asthma. A rotameter FR of 10
L/m to the nebulizer with no flow from a second gas source to a TC (conventional
TNDS) resulted in a significant drop in helium concentration during tidal
breathing (46.2%) and acute asthma (27.5%) due to RAE. This degree of helium
dilution can negate the beneficial effects of heliox to lung mechanics almost
completely. A rotameter FR of 10 L/m each to a nebulizer and a TC resulted in a
helium concentration 69.8% during tidal breathing (no RAE), but 49% (significant
RAE) during asthma events. A rotameter FR of 15 L/m (pressure regulator setting,
100 lbs per square inch) to a TC, while maintaining a rotameter FR of 10 L/m to a
nebulizer prevented RAE during asthma (helium concentration, 69.9%). Conventional
TNDS may be used to deliver the beta-agonist with heliox during asthma without
RAE.
PMID- 17035440
TI - Dynamic hyperinflation during bronchoconstriction in asthma: implications for
symptom perception.
AB - OBJECTIVE: The objective of this study was to examine the relationship between
respiratory symptom intensity and quality and dynamic lung hyperinflation (DH)
during induced bronchoconstriction in asthma. PATIENTS AND METHODS: Subjects with
asthma (n = 116) underwent baseline spirometry and lung volume measurement
followed by high-dose methacholine challenge testing (MCT) [maximum decrease in
FEV(1) of 50% from baseline]. Dyspnea intensity (Borg scale) was measured after
each dose of methacholine. Qualitative descriptors of breathlessness and
functional residual capacity (FRC) were measured at the doses nearest to the
provocative concentration of methacholine causing a 20% fall in FEV (PC(20)) and
at the highest dose of methacholine (maximum response). RESULTS: FEV(1) decreased
by 24.7 +/- 0.7% (mean +/- SEM) at the dose nearest to PC(20) and by 46.1 +/-
1.1% at maximum response. Inspiratory capacity decreased by 0.62 +/- 0.04 L at
the dose nearest to PC(20) and 1.06 +/- 0.06 L at maximum response. The
descriptor clusters "inspiratory difficulty," "chest tightness," "unsatisfied
inspiration," and "work" were selected at the dose nearest to PC(20) but were
more frequently selected at maximum response (p < 0.0001). Individuals who
reported chest tightness at maximum response had greater airflow obstruction and
higher FRC (percentage of predicted) than those who did not report chest
tightness. CONCLUSIONS: Four dominant qualities of dyspnea in asthma (inspiratory
difficulty, chest tightness, unsatisfied inspiration, and work) were reported
early in the course of MCT and evolved in parallel, becoming more prevalent at
maximum response. Significant DH accompanied even mild bronchoconstriction during
MCT in asthma, making it difficult to separate mechanisms of chest tightness from
other dominant respiratory sensations.
PMID- 17035441
TI - Use of inhaled corticosteroids and the risk of fracture.
AB - BACKGROUND: Previous studies have found an association between the use of inhaled
corticosteroids and fracture, but the extent to which this association is due to
inhaled corticosteroids or to related factors, such as the severity of airflow
obstruction, is disputed. We report a new approach in which we combine data on
people with airflow obstruction from a large Medical Research Council study of
the assessment and management of older people in the community with longitudinal
data from their computerized general practice records. METHODS: Our cohort
includes 1,671 study participants with a diagnosis of asthma or COPD (mean age,
80.6 years). We determined the dose-response relationship between inhaled
corticosteroid exposure and time to first fracture using Cox regression, allowing
for a wide range of potential confounding factors. RESULTS: During a mean follow
up period of 9.4 years, 982 patients (59%) received a prescription for an inhaled
corticosteroid and 187 patients had a fracture. After adjusting for the effects
of age and gender, we found a dose-related increase in fracture risk with
exposure to inhaled corticosteroids (rate ratio for mean daily dose > 601 mug,
2.53; 95% confidence interval [CI], 1.65 to 3.89; overall trend p < 0.0001). The
results were similar after adjusting for oral corticosteroid exposure, airflow
obstruction diagnosis, historical fracture, and bronchodilator use (rate ratio,
4.21; 95% CI, 2.19 to 8.13), and also in the subset of people with no exposure to
oral corticosteroids (rate ratio, 4.54; 95% CI, 1.23 to 16.74). CONCLUSIONS: Our
findings provide further evidence that inhaled corticosteroid use is an
independent risk factor for fracture.
PMID- 17035442
TI - Effect of rollator use on health-related quality of life in individuals with
COPD.
AB - OBJECTIVE: The purpose of this study was to evaluate the influence of rollator
use on health-related quality of life in patients with COPD. DESIGN: Randomized
controlled trial. METHODS: Thirty-one postrehabilitation patients with COPD were
randomized to receive a rollator (n = 18) or usual care (n = 13) for 8 weeks and
to record the frequency of rollator use. Outcome measures at baseline, 4 weeks,
and 8 weeks included the Chronic Respiratory Questionnaire (CRQ) and the 6-min
walk (6MW). RESULTS: During acute testing, subjects consistently walked further
when assisted (baseline 6MW: 292 +/- 67 m vs 263 +/- 67 m; 8 weeks: 283 +/- 65 m
vs 259 +/- 68 m [+/-SD]; p = 0.013). However, provision of a rollator at home was
not associated with group differences in the CRQ (p > 0.08) or in the unassisted
6MW (p = 0.4) or the assisted 6MW (p = 0.5). Eight of 18 subjects assigned to the
rollator group used the rollator less than three times per week. Regular users
demonstrated a consistent improvement in mastery compared with infrequent users
(4 weeks: 4.7 +/- 0.6 vs 5.2 +/- 0.8, respectively; 8 weeks: 5.3 +/- 0.8 vs 4.7
+/- 0.4; p = 0.014). CONCLUSIONS: Despite evidence of effectiveness during acute
testing, this study did not demonstrate a rollator effect on quality of life or
exercise capacity when the rollator was provided at home, for a longer period.
Actual use of a rollator may be an important determinant of its effect.
Therefore, when prescribing a rollator, health-care professionals should attempt
to identify those most likely to use it.
PMID- 17035443
TI - Role of gastroesophageal reflux symptoms in exacerbations of COPD.
AB - BACKGROUND AND AIMS: The impact of gastroesophageal reflux disease (GERD) on
exacerbations of COPD has never been evaluated. The aims of this investigation
were to determine the prevalence of gastroesophageal reflux (GER) symptoms in
COPD patients and the effect of GER on the rate of exacerbations of COPD per
year. METHODS: A questionnaire-based, cross sectional survey was performed.
Subjects were recruited from the outpatient pulmonary clinics at the University
of Florida Health Science Center/Jacksonville. Included patients had an
established diagnosis of COPD. Exclusion criteria were respiratory disorders
other than COPD, known esophageal disease, active peptic ulcer disease, Zollinger
Ellison syndrome, mastocytosis, scleroderma, and current alcohol abuse. Those
meeting criteria and agreeing to participate were asked to complete the Mayo
Clinic GERD questionnaire by either personal/telephone interview. Clinically
significant reflux was defined as heartburn and/or acid regurgitation weekly.
Other outcome measures noted were frequency and type of COPD exacerbations.
Statistical analysis was performed using the Fisher exact test for categorical
data and the independent t test for interval data. RESULTS: Eighty-six patients
were enrolled and interviewed (mean age, 67.5 years). Male patients accounted for
55% of the study group. Overall, 37% of patients reported GER symptoms. The mean
FEV(1) percentage of predicted was similar in those with or without GER. The rate
of exacerbations of COPD was twice as high in patients with GER symptoms compared
to those without GER symptoms (3.2/yr vs 1.6/yr, p = 0.02). CONCLUSIONS: The
presence of GER symptoms appears to be associated with increased exacerbations of
COPD.
PMID- 17035444
TI - Epithelial mucin stores are increased in the large airways of smokers with
airflow obstruction.
AB - BACKGROUND: Habitual cigarette smoking is associated with chronic mucus
hypersecretion, but the relationship between mucus abnormalities and airflow
obstruction in smokers is uncertain. METHODS: We collected bronchial biopsy
samples and epithelial brushings from 24 smokers with and without airflow
obstruction and 19 nonsmoking healthy control subjects. Epithelial mucin stores,
mucin immunostains, and goblet cell morphology were quantified in bronchial
biopsy samples using stereology, and mucin gene expression was quantified in
epithelial brushings using real-time reverse transcriptase-polymerase chain
reaction. RESULTS: Goblet cell size and number were higher than normal in smokers
(both p < 0.05), leading to a 2.2-fold increase in the volume of stored mucin in
the epithelium per surface area of basal lamina (1.94 +/- 0.31
microm(3)/microm(2) vs 4.32 +/- 0.55 microm(3)/microm(2) in control subjects vs
smokers, p = 0.001). The increase in stored mucin occurred because of an increase
in MUC5AC (p = 0.018) and despite a decrease in MUC5B (p < 0.0001). Stored mucin
was significantly higher in the subgroup of smokers with airflow obstruction (p =
0.029) and correlated with FEV(1)/FVC even when controlling for diffusing
capacity as a measure of emphysema (p = 0.034). CONCLUSIONS: Epithelial mucin
stores are increased in habitual smokers because of goblet cell hypertrophy and
hyperplasia, and the pattern of mucin gene expression is abnormal. The highest
epithelial mucin stores are found in smokers with airflow obstruction, suggesting
a mechanistic link between epithelial mucin dysregulation and airflow
obstruction.
PMID- 17035445
TI - Impact of a winter respiratory virus season on patients with COPD and association
with influenza vaccination.
AB - BACKGROUND: We assessed the effects of an influenza season on patients with COPD.
Data from 2,215 veterans in a multicenter, randomized, double-blind influenza
vaccine efficacy study were analyzed for changes in spirometric and functional
status, comparing patients with laboratory-documented influenza (LDI)-caused
illness, non-LDI-caused respiratory illness, or no illness, and for association
with influenza vaccination. METHODS: Patients received either IM trivalent
inactivated influenza virus vaccine (TIV) plus intranasal trivalent, live
attenuated, cold-adapted influenza virus vaccine (TC) or TIV plus intranasal
placebo (TP). We performed spirometry, measured the chronic lung disease severity
index (CLDSI) score to assess functional status and well-being, and tested for
influenza virus infection. RESULTS: Worsening in FEV(1), percentage of predicted
FEV(1), and CLDSI score (p < 0.001) was associated with acute respiratory illness
in 585 illnesses including 94 LDI-caused illnesses. LDI-caused illness was more
likely to be associated with worsening in FEV(1) and CLDSI score acutely than non
LDI-caused illness (p < 0.01). Logistic regression showed acute respiratory
illness (odds ratio [OR], 1.78; 95% confidence limit [CL], 1.40 to 2.26) to be
associated with worsening in CLDSI score, and receipt of TC (OR, 1.39; 95% CL,
1.10 to 1.74) and no illness (OR, 0.70; 95% CL, 0.53 to 0.91 for acute
respiratory illness) to be associated with better CLDSI score at the end of the
study. Hospitalization was more frequent in patients with acute respiratory
illness (p < 0.0001). CONCLUSIONS: Acute respiratory illness was associated with
increased health-care utilization and obstruction to airflow, and worse
functional status and well-being. At the end of the study, receipt of TC was
associated with improvement and acute respiratory illness was associated with
worsening in functional status and well-being.
PMID- 17035446
TI - Does quality of life of COPD patients as measured by the generic EuroQol five
dimension questionnaire differentiate between COPD severity stages?
AB - OBJECTIVE: To assess the discriminative properties of the EuroQol five-dimension
questionnaire (EQ-5D) with respect to COPD severity according to Global
Initiative for Chronic Obstructive Lung Disease (GOLD) criteria in a large
multinational study. METHODS: Baseline EQ-5D visual analog scale (VAS) scores, EQ
5D utility scores, and St. George Respiratory Questionnaire scores were obtained
from a subset of patients in the Understanding the Potential Long-term Impact on
Function with Tiotropium trial, which was a 4-year placebo-controlled trial
designed to assess the effect of tiotropium on the rate of decline in FEV(1) in
COPD patients aged > or = 40 years, an FEV(1) of < 70% predicted, an FEV(1)/FVC
ratio of < or = 70%, and a smoking history of >/= 10 pack-years. RESULTS: A total
of 1,235 patients (mean post bronchodilator FEV(1), 48.8% predicted) from 13
countries completed the EQ-5D. The EQ-5D VAS and utility scores differed
significantly among patients in GOLD stages 2, 3, and 4, also after correction
for age, sex, smoking, body mass index (BMI), and comorbidity (p < 0.001). The
mean EQ-5D VAS scores for patients in GOLD stages 2, 3, and 4 were 68 (SD, 16),
62 (SD, 17), and 58 (SD, 16), respectively. The mean utility scores were 0.79
(SD, 0.20) for patients in GOLD stage 2, 0.75 (SD, 0.21) for patients in GOLD
stage 3, and 0.65 (SD, 0.23) for patients in GOLD stage 4. Effect sizes for the
difference in utility scores between patients in GOLD stages 3 and 4 were more
than twice as high as those for the difference between patients in GOLD stages 2
and 3. Gender, postbronchodilator FEV(1) percent predicted, the number of
hospital admissions and emergency department visits in the year prior to baseline
measurements, measures of comorbidity, and BMI were independently associated with
EQ-5D utility. EQ-5D utility scores also differed between patients from different
countries. French patients especially had lower utility scores than US patients.
Utility scores calculated with the US value set were on average 5% higher than
those calculated with the UK value set. CONCLUSIONS: Increasing severity of COPD
was associated with a significant decline in EQ-5D VAS scores and utility scores.
These results demonstrate that a generic instrument can assess COPD impact on
quality of life and that the scores discriminate between patient groups of known
severity. These utility scores will be useful in cost-effectiveness assessments.
PMID- 17035448
TI - Chylothorax complicating repairs of the descending and thoracoabdominal aorta.
AB - BACKGROUND: Chylothorax occurring during thoracic aortic surgery is an infrequent
but serious complication. The purpose of this study was to analyze our experience
with this complication and the resulting outcomes. METHODS: From January 1991 to
July 2005, we performed 1,233 descending thoracic and thoracoabdominal aortic
surgical procedures. A retrospective review was performed to analyze and identify
preoperative and operative risk factors as well as management outcomes of
postoperative chylothorax (PCT). RESULTS: PCT developed in five patients (0.4%).
All five cases occurred with descending thoracic aortic aneurysm repair, and 80%
(four of five patients) were undergoing aortic reoperation. All patients were
managed successfully with no mortality. Risk factors for the development of
chylothorax were descending thoracic aortic repair (p = 0.006) and thoracic
aortic reoperations (p = 0.0003). Nonoperative management was successful in 60%
(three of five patients). Two patients required left thoracotomy with direct
ligation. Mean hospital length of stay was 35 days (range, 15 to 60 days). Mean
follow-up was 33 months (range, 3 to 69 months) with no recurrence of chylothorax
or additional morbidity or mortality. CONCLUSIONS: Chylothorax is more likely to
occur with reoperations and repairs involving the descending thoracic aorta.
Although PCT is associated with longer hospital length of stay, it is not
associated with increased infectious complications. Early identification and
prompt treatment may decrease both early and late morbidity and mortality.
PMID- 17035447
TI - Thirty-year cumulative incidence of chronic bronchitis and COPD in relation to 30
year pulmonary function and 40-year mortality: a follow-up in middle-aged rural
men.
AB - PURPOSE: To describe the 30-year cumulative incidence of chronic bronchitis and
COPD in relation to smoking habits. The effect of chronic bronchitis on pulmonary
function and mortality was also examined. METHODS: Middle-aged men belonging to
two rural Finnish cohorts of the Seven Countries Study (n = 1,711 in 1959) were
followed up for up to 40 years until 2000. Standard questionnaires were used to
measure chronic bronchitis, and repeated spirometry was used to evaluate
pulmonary function during the 30 years. Forty-year mortality data were examined.
RESULTS: The cumulative incidence of chronic bronchitis and COPD was 42% and 32%,
respectively, in continuous smokers, compared to 26% and 14% in ex-smokers and
22% and 12% in never-smokers. During the follow-up, subjects with chronic
bronchitis had on average 252 mL (95% confidence interval, 211 to 293 mL) lower
forced expiratory volume than those without it. The decrease in forced expiratory
volume attributable to chronic bronchitis was most pronounced in those with
persistent symptoms and in smokers. In subjects with chronic bronchitis, all
cause mortality was increased by a hazard ratio of 1.30 (95% confidence interval,
1.02 to 1.65). Smokers with chronic bronchitis who decreased their daily
cigarette consumption increased their median life span by 2.4 years. CONCLUSIONS:
The lifetime risk of chronic bronchitis among smokers is approximately two in
five, and almost one half of smokers who have chronic bronchitis also acquire
COPD. Chronic bronchitis is related to earlier death, also in never-smokers,
probably partly through a rapid decline in pulmonary function.
PMID- 17035449
TI - Nontraumatic disruption of the fibrocartilaginous trachea: causes and clinical
outcomes.
AB - BACKGROUND: Nontraumatic disruption of the fibrocartilaginous trachea is rare,
and the appropriate management of this condition is not well-characterized.
METHODS: Retrospective analysis of the clinical features, causes, and outcomes
with surgical and nonsurgical management in nine adult patients with nontraumatic
fibrocartilaginous tracheal disruption identified by bronchoscopy from January 1,
1975, to December 31, 2004, at a single institution. RESULTS: The most common
cause was external beam radiotherapy (RT) in five patients. Other causes included
postoperative complications of cervical and superior mediastinal operations in
three patients and Aspergillus fumigatus-induced ulcerative tracheobronchitis in
one patient post-lung transplantation. Four patients were treated surgically;
three because of significant pneumomediastinum and one because the size of the
tracheal defect made spontaneous healing seem unlikely. A silicone stent was
placed in one patient for concomitant tracheal narrowing, and one patient was
treated medically with antifungal agents. The remaining three patients were
followed up serially without any intervention. With these treatments, only one
patient died as a consequence of tracheal disruption. Repeat bronchoscopies were
performed in seven of the remaining eight patients and confirmed healing of the
necrotic defect in all. CONCLUSION: Nontraumatic disruption of the
fibrocartilaginous trachea occurs most commonly as a consequence of external beam
RT. It can also occur as a complication of cervical and superior mediastinal
operations or from A fumigatus-induced ulcerative tracheobronchitis post-lung
transplantation. Although surgical treatment has been generally recommended for
patients with this condition, patients with contained disruptions without
evidence of pneumomediastinum may be managed nonoperatively.
PMID- 17035450
TI - Air leaks after lobectomy increase the risk of empyema but not of cardiopulmonary
complications: a case-matched analysis.
AB - PURPOSE: To assess whether the presence and duration of air leaks after lobectomy
are associated with an increased incidence of cardiopulmonary complications.
METHODS: Propensity score analysis was used on 726 patients undergoing pulmonary
lobectomy from 1995 through 2004 to form three well-matched pairs of patients:
patients with prolonged air leak (PAL) [> 7 days] and without air leak; patients
with short air leak (SAL) [< or = 7 days] and without air leak; and patients with
SAL and PAL. These matched groups were then compared to assess postoperative
hospital stay and early outcome. RESULTS: Patients with SAL had a longer
postoperative hospital stay compared to patients without air leak (8.6 days vs
7.8 days, respectively; p < 0.0001) but had similar morbidity and mortality.
Patients with PAL had a longer postoperative hospital stay compared to patients
without air leak (16.2 days vs 8.3 days, respectively; p < 0.0001) and with SAL
(16.9 days vs 9 days, respectively; p < 0.0001), but similar cardiopulmonary
complications were noted between the groups. Patients with PAL had a higher rate
of empyema compared to patients without air leak and with SAL (8.2% vs 0%, p =
0.01 and 10.4% vs.1.1%, p = 0.01, respectively). CONCLUSIONS: The presence of air
leak was not associated with an increased incidence of cardiopulmonary morbidity
but was associated with an increased risk of empyema. Future prospective studies
are needed to confirm safety of fast track in patients with air leak.
PMID- 17035451
TI - Repeated sputum inductions induce a transient neutrophilic and eosinophilic
response.
AB - INTRODUCTION: Sputum induction is a tool to monitor airway inflammation, yet it
may induce by itself a neutrophilic response when repeated within 24 to 48 h.
This limits its repeated use in clinical trials. OBJECTIVE: We aimed to
investigate the induction and resolution of inflammation generated by repeated
sputum inductions. SUBJECTS AND DESIGN: Sixteen healthy intermittent smokers
participated in a study on the short-term effects of smoking. The nonsmoking arm
consisted of seven successive sputum inductions with increasing time intervals
(3, 6, 12, 24, 48, and 96 h). Inflammatory cellular characteristics and different
soluble mediators were investigated. MEASUREMENTS AND RESULTS: The median
percentage of sputum neutrophils increased significantly from baseline to 6 h
(58.9% [range, 31.8 to 94.2%] to 83.2% [range, 26.7 to 98.3%], respectively).
Surprisingly, the percentage of eosinophils also increased significantly from
baseline to 6, 12, 24, and 48 h, as follows: 0.3% (range, 0.0 to 1.2%) to 1.7%
(range, 0.0 to 15.5%), 2.2% (range, 0.5 to 12.5%), 1.2% (range, 0.0 to 4.8%), and
0.8% (range, 0.0 to 2.8%), respectively. Interleukin-8 increased significantly
from baseline to 24 h (1,553 pg/mL [range, 462 to 8,192 pg/mL] to 2,178 pg/mL
[range, 666 to 128,544 pg/mL]). CONCLUSIONS: Repeated sputum inductions should
preferably be avoided within 48 h. It induces not only a short-lived neutrophilic
response but also a prolonged eosinophilic inflammatory response in healthy
subjects, possibly by local changes in osmolarity, and subsequent epithelial
and/or mast cell activation.
PMID- 17035452
TI - Long-term symptom recovery and health-related quality of life in patients with
mild-to-moderate-severe community-acquired pneumonia.
AB - STUDY OBJECTIVES: The long-term outcomes of patients with community-acquired
pneumonia (CAP) in terms of symptom resolution and health-related quality of life
(HRQL) is unknown. Our objective was to determine the rate of symptom resolution
using validated patient-based outcome measures, and to assess HRQL 18 months
after the episode. PARTICIPANTS: Patients were recruited from a group enrolled in
a randomized trial comparing two durations of treatment for CAP. Between 2000 and
2003, we included 102 adults with a mild-to-moderate-severe CAP (pneumonia
severity index, < or = 110). INTERVENTIONS: CAP-related symptoms were assessed
until month 18 using the CAP score. The CAP score was divided into respiratory
and well-being sections to assess the recovery of respiratory and well-being
symptoms separately. The HRQL was assessed at 18 months using the Medical
Outcomes Study 36-item short form (SF-36) questionnaire and compared to a Dutch
reference group. RESULTS: Respiratory symptoms resolved within 14 days, while the
well-being symptoms resolved more slowly. Taking the prepneumonia status into
account, patients recovered fully from pneumonia after 6 months. Patients with
comorbid conditions had significantly more symptoms prepneumonia and during
follow-up than patients without comorbidities, but at all time points the
proportion of patients that reached > or = 80% of the prepneumonia health level
did not depend on comorbidity, age, or etiology. SF-36 scores at 18 months were
significantly impaired in four of the eight dimensions for patients with comorbid
illness, but did not differ from the reference population for patients without
comorbid illness. CONCLUSION: Patients with mild-to-moderate-severe CAP recover
fully from pneumonia after 6 months. The presence of symptoms beyond 28 days and
any impairment in HRQL were found to reflect age and comorbidity rather than the
persistent effects of the pneumonia itself.
PMID- 17035453
TI - Pathophysiology of pneumothorax following ultrasound-guided thoracentesis.
AB - STUDY OBJECTIVES: Pneumothorax following ultrasound-guided thoracentesis is rare.
Our goal was to explain the mechanisms of pneumothorax following ultrasound
guided thoracentesis in a setting where pleural manometry is routinely used.
METHODS: We reviewed the patient records and procedure reports of 401 patients
who underwent ultrasound-guided thoracentesis. When manometry was performed,
pleural space elastance was determined. A model assuming dependence of the
pleural space elastic properties on respiratory system elastic properties was
used to isolate cases with presumed normal pleural space elastance. Elastance
outside mean +/- SD x 2 of the isolated sample was considered abnormal. Four
radiographic criteria of unexpandable lung were used: visceral pleural peel,
lobar atelectasis, basilar pneumothorax, and pneumothorax with ipsilateral shift.
RESULTS: There were 102 diagnostic thoracenteses, 192 therapeutic thoracenteses
with pleural manometry, and 73 therapeutic thoracenteses without manometry. There
was one pneumothorax that occurred from lung puncture and eight unintentional
pneumothoraces, all of which showed radiographic evidence of unexpandable lung.
Four of eight unintentional pneumothoraces had abnormal elastance; none had
excessively negative pleural pressure (< -25 cm H(2)O). CONCLUSIONS:
Unintentional pneumothoraces cannot be prevented by monitoring for symptoms or
excessively negative pressure. These pneumothoraces were drainage related rather
than due to penetrating lung trauma or external air introduction. We speculate
that unintentional pneumothoraces are caused by transient, parenchymal-pleural
fistulae caused by nonuniform stress distribution over the visceral pleura that
develop during large-volume drainage if the lung cannot conform to the shape of
the thoracic cavity in some patients with unexpandable lung. These fistulae
appear to be pressure dependent, and the resulting pneumothoraces rarely require
treatment. Drainage-related pneumothorax is an unavoidable complication of
ultrasound-guided thoracentesis and appears to account for the vast majority of
pneumothoraces occurring in a procedure service.
PMID- 17035454
TI - The safety of bronchoscopy in a pulmonary fellowship program.
AB - STUDY OBJECTIVE: To determine the complication rate from supervised training
bronchoscopy in a single pulmonary fellowship program, and to examine the effects
of fellow and faculty experience on this complication rate. DESIGN: A
retrospective review of preexisting quality improvement data from one center for
the time period July 1, 1991, until June 30, 2005, was performed. The data were
stratified based on the fellow year group and the staff experience level. The
types of complications were recorded. SETTING: The study was performed at an
accredited pulmonary and critical care fellowship program at a military medical
center in the United States. PARTICIPANTS: Fifty-one pulmonary and critical care
medicine fellows and 20 staff supervising physicians performed the bronchoscopies
that were included in this study. RESULTS: A total of 3,538 training
bronchoscopies were performed during the study period with 73 complications for a
complication rate of 2.06%. The most common complication was pneumothorax. The
overall complication rates for first-year fellows (1stYFs), second-year fellows,
and third-year fellows were not significantly different from the total
complication rate. Training bronchoscopies supervised by junior staff had a
complication rate not significantly different from that of senior staff. The
cumulative complication rate for the first trimester for 1stYFs was 3.1%, whereas
the cumulative complication rate for the second plus the third trimester for
1stYFs was 1.57% (p < 0.05). CONCLUSIONS: Training bronchoscopy performed during
a pulmonary fellowship is a safe procedure in a supervised setting. Patients
undergoing bronchoscopy performed by novice bronchoscopists have an increased
complication rate during the first trimester of bronchoscopist training.
PMID- 17035455
TI - Differentiating peripheral pulmonary lesions based on images of endobronchial
ultrasonography.
AB - PURPOSE: To attempt to develop a simple method to discriminate between neoplasm
and nonneoplasm peripheral pulmonary lesions based on images of endobronchial
ultrasonography (EBUS). METHODS: Between June 2004 and June 2005, 151 patients
with bronchoscopic peripheral lesions that could not be detected via a
conventional bronchoscope underwent EBUS for advanced localization with a 20-MHz
miniature radial probe in a tertiary-referral teaching hospital. The image
characteristics were applied subsequently to correlate definite histopathologic
results in studied patients. RESULTS: Based on an initial 20 consecutive patients
with a definite diagnosis, four image characteristics were issued: (1) continuous
hyperechoic margin outside the lesion, (2) homogeneous, or heterogeneous internal
echoes, (3) hyperechoic dots in the lesion, and (4) concentric circles along the
echo probe. In the following 131 patients, excluding five cases due to
inconsistent typing, 93 patients (73.8%) established a diagnosis later. Most
cases involving the image characteristics of homogenous internal echoes and
concentric circles had nonneoplasm lesions (18 of 19 cases, 94.7%, and 14 of 16
cases, 87.5%, respectively). The difference shown in these two respects with
neoplasm lesions was significant by univariate analysis (p < 0.001), although
only concentric circles had a significant p value after multivariate analysis.
Another two image patterns (continuous hyperechoic margins and hyperechoic dots)
did not yield a significant difference (p = 0.090 and p = 0.079, respectively).
The average additional time for EBUS was 3.94 min (1.5 to 10 min). CONCLUSION:
EBUS can provide characteristic information to differentiate the nature of a
peripheral pulmonary lesion from the image characteristics of concentric circles.
PMID- 17035456
TI - The current treatment of pulmonary arterial hypertension: time to redefine
success.
AB - In the past decade, three classes of medications have been approved for the
treatment of pulmonary arterial hypertension. A review of the clinical trial data
for the prostanoids, endothelin antagonists, and phosphodiesterase-5 inhibitors
has shown that all agents have similar efficacy on the 6-min walk distance over
12 to 16 weeks, which was the primary end point in the randomized clinical
trials. However, little is known about their long-term efficacy or about how
these drugs affect the underlying disease, if at all. Successful therapy is
currently defined as an improvement in exercise tolerance over a 4-month period.
Future trials need to better characterize how therapies affect the pulmonary
vasculature pathologically, biologically, and hemodynamically, and whether
survival is actually improved.
PMID- 17035457
TI - How viral infections cause exacerbation of airway diseases.
AB - Exacerbations of asthma and COPD are major causes of morbidity, mortality, and
health-care costs. Over the last decade, studies using new molecular diagnostic
techniques have established that respiratory viruses are a major cause of
exacerbations of both asthma and COPD. The most prevalent viruses detected during
exacerbations are the rhinoviruses. Despite the burden of disease associated with
exacerbations, little is known about the mechanisms of virus-induced
exacerbations of airway diseases. Exacerbations are associated with increased
airway inflammation in patients with both asthma and COPD, but many questions
remain unanswered regarding the key inflammatory cells and mediators involved.
Identifying the key inflammatory mediators involved in exacerbations holds the
promise of developing diagnostic and prognostic markers of exacerbation. In
addition, such studies can identify new therapeutic targets for the development
of novel drugs for the prevention and treatment of exacerbations.
PMID- 17035458
TI - Advances in chemotherapy of non-small cell lung cancer.
AB - In the United States, lung cancer kills more men and woman than the next three
most common cancers combined. Unfortunately, the long-term outcome of lung cancer
is still dismal with a 5-year survival rate of 15%. However, significant
improvements in median survival times and 1-year and 2-year survival rates have
been achieved in the last decade. This progress has been accomplished not only
because of better surgical techniques but also because of the use of platinum
based regimens with newer chemotherapy agents and, more recently, targeted
therapy. The role of chemotherapy as an integral part of the treatment of lung
cancer has expanded significantly, particularly in the last few years with the
proven benefit of adjuvant chemotherapy. For advanced stage non-small cell lung
cancer (NSCLC), chemotherapy prolongs survival and improves quality of life in
patients with good performance status, and appears to provide symptomatic
improvement in patients with decreased performance status. Platinum-based doublet
chemotherapy regimens are now the standard of care in patients with advanced
stage NSCLC, and non-platinum-based combination therapies are reasonable
alternatives in certain populations. The combination of the vascular endothelial
growth factor inhibitor bevacizumab and chemotherapy has proven to prolong
survival. As agents such as monoclonal antibodies, small molecules inhibitors of
tyrosine kinase, and direct inhibitors of proteins involved in lung cancer
proliferation are being developed and tested, we are optimistic that these agents
will result in improvement in the survival and quality of life of lung cancer
patients.
PMID- 17035459
TI - Diagnostic usefulness of B-type natriuretic peptide and functional consequences
of muscle alterations in COPD and chronic heart failure.
AB - COPD affects up to one third of patients with chronic heart failure. The
coexistence of COPD and chronic heart failure presents clinicians with diagnostic
and therapeutic challenges. Measurement of B-type natriuretic peptide plasma
levels facilitates the diagnosis of acute dyspnea in patients known to have both
COPD and chronic heart failure. Patients with COPD or chronic heart failure have
skeletal muscle abnormalities that limit functional capacity independently from
primary organ failure. Exercise training reverses skeletal muscle abnormalities
in patients with COPD or chronic heart failure and may be particularly indicated
in patients with coexistent COPD and chronic heart failure.
PMID- 17035460
TI - Smoking cessation counseling: a practice management perspective.
AB - Individuals continue to smoke despite its numerous proven adverse health effects.
Now viewed as a chronic medical condition, health-care professionals are more
involved in cessation efforts. Physicians are often the first line of defense,
providing intervention through prescription management and counseling. Some
insurers recognize these efforts as health promoting and cost saving, revising
policies to include reimbursement. This article addresses the most recent smoking
cessation policy revision implemented by the Centers for Medicare and Medicaid
Services.
PMID- 17035461
TI - The expanding spectrum of Mycobacterium avium complex-associated pulmonary
disease.
AB - Nontuberculous mycobacteria (NTM) are increasingly recognized as important
pulmonary pathogens. Mycobacterium avium intracellulare complex (MAC) causes most
lung infections due to NTM. Patients with preexisting lung disease or
immunodeficiency are at greatest risk for developing MAC infection. The majority
of MAC pulmonary cases, however, occur in immunocompetent elderly women in
association with nodular infiltrates and bronchiectasis. More recently, pulmonary
disease has also been described in immunocompetent patients after exposure to MAC
contaminated hot tubs. We describe a case of aggressive MAC lung disease in a
young immunocompetent female patient without preexisting lung disease whose
clinical and pathologic characteristics do not fit into any of these categories
and may represent a unique manifestation of MAC lung disease.
PMID- 17035462
TI - A 37-year-old woman with multiple pulmonary nodular opacities and hemoptysis.
PMID- 17035463
TI - Recurrent dyspnea on exertion in a 71-year-old man with prior pulmonary embolism.
PMID- 17035464
TI - A 48-year-old woman with multiple pulmonary nodules and a right ventricular mass.
PMID- 17035466
TI - Documenting research in scientific articles: guidelines for authors: reporting
research designs and activities.
PMID- 17035465
TI - A review of pediatric nonrespiratory sleep disorders.
AB - Sleep problems are extremely common during childhood, from infancy to
adolescence. Despite the prevalence of sleep problems, childhood sleep disorders
are often underrecognized and undiagnosed, despite being either preventable or
treatable. Sleep impacts almost all aspects of a child's functioning, and thus
the increased recognition and treatment of sleep disorders will positively affect
a child's well-being. Children experience the same broad range of sleep
disturbances encountered in adults, including sleep apnea, insomnia, parasomnia,
delayed sleep phase, narcolepsy, and restless legs, but their clinical
presentation, evaluation, and management may differ. Although snoring and sleep
apnea may be the most common indication for an overnight sleep study in a child,
one quarter of children presenting to a sleep clinic for evaluation will have a
second sleep diagnosis, which is often nonrespiratory in nature. Especially in
children, ruling out sleep apnea is rarely the end point of the sleep evaluation.
Clinicians involved in sleep medicine must be prepared to recognize, evaluate,
and manage plans for sleep disorders across the lifespan of the patient. This
article will provide an updated review of nonrespiratory pediatric sleep
disorders within a developmental framework.
PMID- 17035467
TI - A 70-year-old man with migratory pulmonary infiltrates.
PMID- 17035468
TI - Is the more (intricate) the better?
PMID- 17035469
TI - d-ROMs test detects ceruloplasmin, not oxidative stress.
PMID- 17035470
TI - Is endobronchial ultrasound necessary for transbronchial lung biopsy in solitary
pulmonary nodule?
PMID- 17035471
TI - Is intensive insulin therapy safe in the critically ill?
PMID- 17035472
TI - Evaluation of the causes of racial disparity in surgical treatment of early-stage
lung cancer.
PMID- 17035473
TI - Left ventricular diastolic abnormalities in obese subjects.
PMID- 17035474
TI - Severe sepsis due to melioidosis.
PMID- 17035475
TI - Attention to doping controls required when prescribing for athletes.
PMID- 17035476
TI - Respiratory research output.
PMID- 17035477
TI - Complete response following preoperative chemotherapy for resectable non-small
cell lung cancer.
PMID- 17035478
TI - Is bronchoscopy dangerous in the pretreatment workup of non-small cell lung
cancer patients?
PMID- 17035479
TI - Eccentric overload training in patients with chronic Achilles tendinopathy: a
systematic review.
AB - BACKGROUND: Eccentric overload training seems to be a promising conservative
intervention in patients with chronic Achilles tendinopathy. The efficacy of
eccentric overload training on the outcome measures of pain and physical
functioning are not exactly clear. STUDY DESIGN: Systematic review of the
literature. METHODS: Electronic databases were searched for randomised clinical
trials concerning eccentric overload training in patients with chronic Achilles
tendinopathy. The Delphi list was used to assess the methodological quality of
the studies. RESULTS: Nine clinical trials were included. Only one study had
sufficient methodological quality. The included trials showed an improvement in
pain after eccentric overload training. Because of the methodological
shortcomings of the trials, no definite conclusion can be drawn concerning the
effects of eccentric overload training in patients with chronic Achilles
tendinopathy. CONCLUSION: The effects of eccentric exercise training in patients
with chronic Achilles tendinopathy on pain are promising; however, the magnitude
of the effects cannot be determined. Large, methodologically sound studies from
multiple sites in which functional outcome measures are included are warranted.
PMID- 17035480
TI - Notice of redundant publication. Tendon and paratendon Achilles microcirculation
in eccentric training and an Achilles wrap in insertional and mid-portion
tendinopathy--a randomized trial.
PMID- 17035482
TI - TCDD-induced alterations in gene expression profiles of the developing mouse paw
do not influence morphological differentiation of this potential target tissue.
AB - The aryl-hydrocarbon receptor (AhR) is a ligand-dependent transcription factor
that mediates the toxicity of certain halogenated aromatic hydrocarbons including
2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD). These compounds are potent
developmental toxicants that can alter gene expression and disrupt processes of
proliferation and differentiation. It has not yet been determined which tissues
during development are most sensitive to these compounds, nor which genes are
directly associated with the toxicities. We developed a transgenic (TG) mouse
model to delineate the temporal and spatial context of transcriptionally active
AhR by utilizing a dioxin responsive element-linked LacZ reporter system. The
present study focuses on the pattern of TCDD-induced transgene expression
localized to the footpad and digits of the paws between gestational days (GD) 13
and 18. Paw morphology was evaluated at several developmental stages following
TCDD exposure. Gene expression profiles acquired by microarray technology were
evaluated in the paws of fetuses exposed at GD 14.5. The results showed that TCDD
exposure in utero induced LacZ expression in the developing paws. This expression
appeared to be localized to the mesenchymal cell layer. Gross morphological
changes were not observed in the paws prior to or after birth following TCDD
exposure in utero. However, significant alterations in gene expression profiles
in the developing paws were observed at 24 h following TCDD exposure in utero.
These results indicate that the developing paw is a target tissue of TCDD in
terms of altered gene expression, further validating the use of this AhR
responsive reporter gene TG mouse model in studying AhR ligand-mediated
responsiveness. However, the linkage of these changes to detectable biological
outcomes in the paw remains unclear.
PMID- 17035481
TI - Effects of rugby sevens matches on human neutrophil-related non-specific
immunity.
AB - AIMS: To evaluate the influences of the accumulative effect of two consecutive
rugby sevens matches (Sevens) on aspects of human neutrophil-related non-specific
immunity. METHODS: In seven players participating in the Japan Sevens, neutrophil
reactive oxygen species (ROS) production capability and phagocytic activity were
measured using flow cytometry, and serum opsonic activity (SOA) was assessed by
measuring neutrophil ROS using the peak height of lucigenin-dependent
chemiluminescence before and after two consecutive matches. RESULTS: ROS showed
no change immediately after the first match, and had significantly (P<0.05)
increased 4 h later, but showed a decrease after the second match. Phagocytic
activity showed no change immediately after the first match, but had
significantly (P<0.01) decreased 4 h later, and showed a further decrease after
the second match, although it was not significant. SOA significantly (P<0.01)
increased after the first match, and still maintained its high 4 h later, but
decreased after the second match. ROS production capability, phagocytic activity
and SOA significantly (P<0.01) decreased after the second match. CONCLUSIONS:
When rugby players play two consecutive Sevens matches, the exercise loading is
thought to be hard, similar to that experienced during a marathon race and
intensive or long training in a training camp, although the expected changes were
not seen after the first match. Differences between after the first and the
second matches may be due to the "cumulative effect".
PMID- 17035483
TI - A photogrammetric technique for the analysis of palatal three-dimensional changes
during rapid maxillary expansion.
AB - The aim of this study was to assess, by a digital photogrammetric technique, the
relative dimensional changes before and after rapid maxillary expansion (RME).
The transverse diameters and volumetric variations of the palate were measured by
photogrammetry on study casts taken at three different phases of therapy: at the
beginning of treatment (T1), on removal of the rapid expander, after expansion
and retention for three months (T2), and six months after appliance removal (T3).
The sample consisted of 30 children, (age range 7-8 years), all with a crossbite;
15 were angle Class I, six Class II and nine Class III. They were treated with an
acrylic splint expander with two turns per day until the maxillary molar palatal
cusps were in contact with the mandibular molar buccal cusps. The RME device was
used as a passive retainer for three months, after which it was removed. During
the following six months, no retention was used and no orthodontic treatment was
undertaken. The findings demonstrated a significant relapse (P < 0.001) in the
dental transverse diameter in all patients six months after appliance removal,
although the palatal volume remained stable.
PMID- 17035484
TI - How do we evaluate the economics of health care?
AB - Economic evaluation has become an integral component of health service research
in recent years and will no doubt become more influential. As resources are
reduced in health services, more questions are likely to be asked on the costs
and benefits of new treatments. Questions are also likely to be aimed at
treatments that are currently provided. Economics related to health care is
complex and numerous methods of economic evaluation exist. Full economic
evaluation involves the assessment of both costs and outcomes and is ideal for
comparing the efficiency of treatments. Partial evaluations can also provide
useful information on the contribution of component costs to treatment costs as a
whole. The aim of this review is to assess the various methods available to
evaluate the economics of health care and to place in context how these methods
may be used within dentistry.
PMID- 17035485
TI - In vitro toxicity evaluation of silver soldering, electrical resistance, and
laser welding of orthodontic wires.
AB - The long-term effects of orthodontic appliances in the oral environment and the
subsequent leaching of metals are relatively unknown. A method for determining
the effects of various types of soldering and welding, both of which in turn
could lead to leaching of metal ions, on the growth of osteoblasts, fibroblasts,
and oral keratinocytes in vitro, is proposed. The effects of cell behaviour of
metal wires on osteoblast differentiation, expressed by alkaline phosphatase
(ALP) activity; on fibroblast proliferation, assayed by the 3-(4,5
dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenil)-2H
tetrazolium-phenazine ethosulphate method; and on keratinocyte viability and
migration on the wires, observed by scanning electron microscopy (SEM), were
tested. Two types of commercially available wires normally used for orthodontic
appliances, with a similar chemical composition (iron, carbon, silicon, chromium,
molybdenum, phosphorus, sulphur, vanadium, and nitrogen) but differing in nickel
and manganese content, were examined, as well as the joints obtained by
electrical resistance welding, traditional soldering, and laser welding. Nickel
and chromium, known as possible toxic metals, were also examined using pure
nickel- and chromium-plated titanium wires. Segments of each wire, cut into
different lengths, were added to each well in which the cells were grown to
confluence. The high nickel and chromium content of orthodontic wires damaged
both osteoblasts and fibroblasts, but did not affect keratinocytes. Chromium
strongly affected fibroblast growth. The joint produced by electrical resistance
welding was well tolerated by both osteoblasts and fibroblasts, whereas
traditional soldering caused a significant (P < 0.05) decrease in both osteoblast
ALP activity and fibroblast viability, and prevented the growth of keratinocytes
in vitro. Laser welding was the only joining process well tolerated by all tested
cells.
PMID- 17035486
TI - Significance of low positive scores obtained with a method other than
acceleration in the BDProbeTec-Strand displacement amplification test for
detection of Neisseria gonorrhoeae.
PMID- 17035487
TI - Direct detection of Mycobacterium tuberculosis complex DNA and rifampin
resistance in clinical specimens from tuberculosis patients by line probe assay.
AB - The INNO-LiPA.Rif TB test (LiPA) has only been applied to a limited number of
clinical specimens. To assess the utility of this test for detecting
Mycobacterium tuberculosis complex DNA and rifampin (RMP) resistance, 420 sputum
samples comprising specimens from untreated (n=160) and previously treated
(n=260) patients from 11 countries in Asia, Africa, Europe, and Latin America
were tested. DNA was extracted from sputum samples by using a modification of the
Boom's method, while the rpoB core region was amplified by nested PCR. The
results were analyzed in conjunction with those obtained by Ziehl-Neelsen (ZN)
microscopy and by culture on solid media. The LiPA test was positive for M.
tuberculosis complex DNA in 389 (92.9%) specimens, including 92.0% (286 of 311)
ZN-positive and 94.5% (103 of 109) ZN-negative specimens. Of these, 30.6% were
RMP resistant. In contrast, 74.3% of the specimens were positive for M.
tuberculosis by culture, and 30.8% of them were RMP resistant. LiPA detected M.
tuberculosis complex DNA in 92.4% (110 of 119) of the culture-positive and 100.0%
(41 of 41) of the culture-negative specimens from untreated patients. There was a
99.6% concordance between the RMP resistance as determined by culture and by the
LiPA test. With an optimal DNA extraction method, LiPA allows rapid detection of
M. tuberculosis complex DNA and RMP resistance directly from sputum specimens.
LiPA can still provide useful information when culture fails for various reasons.
The rapid availability of this information is necessary to adjust patient
treatment and avoid the risk of amplification of drug resistance.
PMID- 17035488
TI - Use of smear-positive samples to assess the PCR-based genotype MTBDR assay for
rapid, direct detection of the Mycobacterium tuberculosis complex as well as its
resistance to isoniazid and rifampin.
AB - Isoniazid (INH) and rifampin (RIF) are two of the most important antituberculosis
drugs, and resistance to both of these drugs can often result in treatment
failure and fatal clinical outcome. Resistance to these two first-line drugs is
most often attributed to mutations in the katG, inhA, and rpoB genes.
Historically, the identification and testing of the susceptibility of
Mycobacterium tuberculosis complex (MTBC) strains takes weeks to complete. Rapid
detection of resistance using the PCR-based Genotype MTBDR assay (Hain
Lifescience GmbH, Nehren, Germany) has the potential to significantly shorten the
turnaround time from specimen receipt to reporting of results of susceptibility
testing. Therefore, the aim of the present study was to determine (i) the
sensitivity and accuracy of the Genotype MTBDR assay for the detection of MTBC
strains and (ii) the ability of the assay to detect the presence of INH and RIF
resistance-associated mutations in katG and rpoB from samples taken directly from
smear-positive clinical specimens. The results were compared with those obtained
with the reference BACTEC 460TB system combined with standard DNA sequencing
analysis methods for katG, inhA, and rpoB. A total of 92 drug-resistant and 51
pansusceptible smear-positive specimens were included in the study. The Genotype
MTBDR assay accurately and rapidly detected MTBC strains in 94.4% of the 143
specimens and showed a sensitivity of 94.4% for katG and 90.9% for rpoB when used
directly on smear-positive specimens. The assay correctly identified INH
resistance in 48 (84.2%) of the 57 specimens containing strains with resistance
to high levels of INH (0.4 microg/ml) and RIF resistance in 25 (96.2%) of the 26
specimens containing RIF-resistant strains.
PMID- 17035489
TI - Borrelia burgdorferi genetic markers and disseminated disease in patients with
early Lyme disease.
AB - Three genetic markers of Borrelia burgdorferi have been associated with
disseminated disease: the OspC type, the 16S-23S rRNA intergenic spacer type
(RST), and vlsE. Here, we modified previous methods so as to identify the three
markers by PCR and restriction fragment length polymorphism in parallel, analyzed
B. burgdorferi isolates from erythema migrans (EM) skin lesions in 91 patients,
and correlated the results with evidence of dissemination. OspC type A was found
approximately twice as frequently in patients with disseminated disease, whereas
type K was identified approximately twice as often in those without evidence of
dissemination, but these trends were not statistically significant. The remaining
seven types identified were found nearly equally in patients with or without
evidence of dissemination. RST 1 strains were significantly associated with
dissemination (P=0.03), whereas RST 2 and RST 3 strains tended to have an inverse
association with this outcome. The vlsE gene was identified in all 91 cases,
using primer sets specific for an N-terminal sequence of B. burgdorferi strain
B31 (vlsEB31) or strain 297 (vlsE297), but neither marker was associated with
dissemination. Specific combinations of the three genetic markers usually
occurred together. OspC type A was always found with RST 1 and vlsEB31, type K
was always identified with RST 2 and more often with vlsE297, and types E and I
were almost always found with RST 3 and equally often with vlsEB31 and vlsE297.
We conclude that B. burgdorferi strains vary in their capacity to disseminate,
but almost all strains isolated from EM lesions sometimes caused disseminated
disease.
PMID- 17035490
TI - Characterization of a Brucella sp. strain as a marine-mammal type despite
isolation from a patient with spinal osteomyelitis in New Zealand.
AB - Naturally acquired infection of humans with a marine mammal-associated Brucella
sp. has only been reported once previously in a study describing infections of
two patients from Peru. We report the isolation and characterization of a strain
of Brucella from a New Zealand patient that appears most closely related to
strains previously identified from marine mammals. The isolate was preliminarily
identified as Brucella suis using conventional bacteriological tests in our
laboratory. However, the results profile was not an exact match, and the isolate
was forwarded to four international reference laboratories for further
identification. The reference laboratories identified the isolate as either B.
suis or B. melitensis by traditional bacteriological methods in three
laboratories and by a molecular test in the fourth laboratory. Molecular
characterization by PCR, PCR-restriction fragment length polymorphism, and DNA
sequencing of the bp26 gene; IS711; the omp genes omp25, omp31, omp2a, and omp2b;
IRS-PCR fragments I, III, and IV; and five housekeeping gene fragments was
conducted to resolve the discrepant identification of the isolate. The isolate
was identified to be closely related to a Brucella sp. originating from a United
States bottlenose dolphin (Tursiops truncatus) and common seals (Phoca vitulina).
PMID- 17035491
TI - Genotyping of clinical herpes simplex virus type 1 isolates by use of restriction
enzymes.
AB - Recently, three distinct genotypes of clinical herpes simplex virus type 1 (HSV
1) isolates were identified based on DNA sequence information and phylogenetic
analysis of clinical isolates and laboratory strains. We utilized single
nucleotide polymorphism within the genes coding for glycoproteins G and I for
rapid genotype classification by PCR and restriction enzyme cleavage. The method
is suitable for high-scale genotyping of clinical HSV-1 isolates and for the
detection of recombinants.
PMID- 17035493
TI - Rapid simultaneous detection by real-time PCR of cytomegalovirus UL97 mutations
in codons 460 and 520 conferring ganciclovir resistance.
AB - Ganciclovir (GCV) resistance is an emerging problem for transplant recipients. A
sensitive and rapid real-time PCR approach for simultaneous and semiquantitative
detection of human cytomegalovirus (HCMV) UL97 mutations in codons 460/520 was
established by LightCycler and confirmed by restriction fragment length
polymorphism and sequencing. Results from HCMV laboratory strains were compared
with results from 11 GCV-resistant clinical isolates.
PMID- 17035492
TI - tcdC genotypes associated with severe TcdC truncation in an epidemic clone and
other strains of Clostridium difficile.
AB - Severe Clostridium difficile associated disease is associated with outbreaks of
the recently described BI/NAP1 epidemic clone. This clone is characterized by an
18-bp deletion in the tcdC gene and increased production of toxins A and B in
vitro. TcdC is a putative negative regulator of toxin A&B production. We
characterized tcdC genotypes from a collection of C. difficile isolates from a
hospital that experienced an outbreak caused by the BI/NAP1 epidemic clone.
Sequence analysis of tcdC was performed on DNA samples isolated from 199
toxigenic C. difficile isolates (31% BI/NAP1) from 2001 and 2005. Sequences
obtained from 36 (18.6%) isolates predicted wild-type TcdC (232 amino acid
residues), whereas 12 (6.1%) isolates had tcdC genotypes with previously
described 18- or 39-bp deletions. The remaining isolates comprised 15 unique
genotypes. Of these, 5 genotypes contain 18- or 36-bp deletions. Of these five
genotypes, one is characterized by a single nucleotide deletion at position 117
resulting in a frameshift that introduces a stop codon at position 196,
truncating the predicted TcdC to 65 amino acid residues. All 62 of the isolates
in this collection comprising the epidemic clone are characterized by this
genotype. This result suggests that severe truncation of TcdC is responsible for
the increased toxin production observed in strains belonging to the BI/NAP1 clone
and that the 18-bp deletion is probably irrelevant to TcdC function. Further
investigations are required to determine the effect of this and other tcdC
genotypes on toxin production and clinical disease.
PMID- 17035494
TI - Feasibility of freeze-dried sera for serological and molecular biological
detection of hepatitis B and C viruses.
AB - We compared hepatitis B virus (HBV) surface antigen, anti-hepatitis C virus (HCV)
antibody, and HCV RNA quantification in frozen and freeze-dried serum samples to
assess the usefulness of freeze-dried sera for detection of HBV and HCV. The
results indicated that freeze-dried sera as well as frozen sera can be useful for
serological and molecular biological analyses of HBV and HCV.
PMID- 17035495
TI - Molecular method for identification of Rickettsia species in clinical and
environmental samples.
AB - We present a PCR method targeting the 23S-5S internal transcribed spacer coupled
with reverse line blotting that allows Rickettsia species detection and
identification in a single step. The method is highly sensitive and specific in
identifying Rickettsia species from both patient and environmental samples. The
generic approach used allowed us to identify new pathogens.
PMID- 17035496
TI - Not so pretty in pink: Staphylococcus cohnii masquerading as methicillin
resistant Staphylococcus aureus on chromogenic media.
PMID- 17035497
TI - Phylogenetic analysis of "Candidatus Mycoplasma turicensis" isolates from pet
cats in the United Kingdom, Australia, and South Africa, with analysis of risk
factors for infection.
AB - Two hemotropic mycoplasmas have been recognized in cats, Mycoplasma haemofelis
and "Candidatus Mycoplasma haemominutum." We recently described a third feline
hemoplasma species, designated "Candidatus Mycoplasma turicensis," in a Swiss cat
with hemolytic anemia. This isolate induced anemia after experimental
transmission to two specific-pathogen-free cats and analysis of the 16S rRNA gene
revealed its close relationship to rodent hemotropic mycoplasmas. The agent was
recently shown to be prevalent in Swiss pet cats. We sought to investigate the
presence and clinical importance of "Candidatus Mycoplasma turicensis" infection
in pet cats outside of Switzerland and to perform the molecular characterization
of isolates from different countries. A "Candidatus Mycoplasma turicensis"
specific real-time PCR assay was applied to blood samples from 426 United Kingdom
(UK), 147 Australian, and 69 South African pet cats. The 16S rRNA genes of
isolates from different countries were sequenced and signalment and laboratory
data for the cats were evaluated for associations with "Candidatus Mycoplasma
turicensis" infection. Infections were detected in samples from UK, Australian,
and South African pet cats. Infection was associated with the male gender, and
"Candidatus Mycoplasma haemominutum" and M. haemofelis coinfection. Coinfected
cats exhibited significantly lower packed cell volume (PCV) values than
uninfected cats. Phylogenetic analyses revealed that some Australian and South
African "Candidatus Mycoplasma turicensis" isolates branched away from the
remaining isolates. In summary, "Candidatus Mycoplasma turicensis" infection in
pet cats exists over a wide geographical area and significantly decreased PCV
values are observed in cats coinfected with other feline hemoplasmas.
PMID- 17035499
TI - Emergence of ofloxacin resistance in Mycobacterium tuberculosis clinical isolates
from China as determined by gyrA mutation analysis using denaturing high-pressure
liquid chromatography and DNA sequencing.
AB - A high rate of double point mutations in gyrA (56% of 87 ofloxacin-resistant
Mycobacterium tuberculosis clinical isolates) indicates the emergence of
fluoroquinolone resistance. This is the first report to describe denaturing high
pressure liquid chromatography analysis of mutations in gyrA of M. tuberculosis
in a large number of clinical isolates.
PMID- 17035498
TI - Evaluation of Entamoeba histolytica antigen and antibody point-of-care tests for
the rapid diagnosis of amebiasis.
AB - The bedside diagnosis of amebiasis could improve patient care. In Bangladesh and
Vietnam, a novel and simple-to-use Entamoeba histolytica rapid antigen test had
97% sensitivity and 100% specificity compared to the results of a standard enzyme
linked immunosorbent assay antigen detection method, and a rapid antibody test
had 89 to 100% sensitivity and 89 to 95% specificity.
PMID- 17035500
TI - Relationship between preexisting anti-varicella-zoster virus (VZV) antibody and
clinical VZV reactivation in hematopoietic stem cell transplantation recipients.
AB - Reactivation of latent varicella-zoster virus (VZV), presenting as localized
zoster or as disseminated infection, is a common and potentially serious
complication in hematopoietic stem cell transplantation (HSCT) recipients. We
retrospectively studied anti-VZV immunoglobulin G titers by the immune adherence
hemagglutination method after HSCT and also studied VZV DNA by real-time PCR
during clinical VZV reactivation using cryopreserved serum samples. No
significant difference was found between anti-VZV titers in 13 patients with VZV
infection (localized zoster in 11 patients and disseminated zoster in 2 patients)
and in 13 subjects without VZV infection at each time point after HSCT.
Preexisting anti-VZV titers of disseminated zoster cases tended to be lower than
those of localized zoster cases (P=0.10). Serum VZV DNA copy numbers at the onset
of disseminated zoster cases tended to be higher than those of localized zoster
cases (P=0.09). A strong inverse correlation was found between preexisting anti
VZV titer and serum VZV DNA at onset (r=-0.90, P=0.006). In HSCT recipients,
preexisting antibody does not prevent the development of VZV reactivation but may
contribute to decreased viral load at onset, resulting in a mild clinical course.
PMID- 17035502
TI - Calcium regulation of chloroplast protein translocation is mediated by calmodulin
binding to Tic32.
AB - The import of nuclear-encoded proteins into chloroplasts is tightly controlled on
both sides of the envelope membranes. Regulatory circuits include redox-control
as well as calcium-regulation, with calmodulin being the likely mediator of the
latter. Using affinity-chromatography on calmodulin-agarose, we could identify
the inner envelope translocon component Tic32 as the predominant calmodulin
binding protein of this membrane. Calmodulin-binding assays corroborate the
interaction for heterologously expressed as well as native Tic32. The interaction
is calcium-dependent and is mediated by a calmodulin-binding domain between Leu
296 and Leu-314 close to the C-proximal end of the pea Tic32. We furthermore
could establish Tic32 as a bona fide NADPH-dependent dehydrogenase. NADPH but not
NADH or NADP(+) affects the interaction of Tic110 with Tic32 as well as Tic62. At
the same time, dehydrogenase activity of Tic32 is affected by calmodulin. In
particular, binding of NADPH and calmodulin to Tic32 appear to be mutually
exclusive. These results suggest that redox modulation and calcium regulation of
chloroplast protein import convene at the Tic translocon and that both could be
mediated by Tic32.
PMID- 17035501
TI - Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion,
embryonic lethality, CNS malformations, and anemia.
AB - SLC25A19 mutations cause Amish lethal microcephaly (MCPHA), which markedly
retards brain development and leads to alpha-ketoglutaric aciduria. Previous data
suggested that SLC25A19, also called DNC, is a mitochondrial deoxyribonucleotide
transporter. We generated a knockout mouse model of Slc25a19. These animals had
100% prenatal lethality by embryonic day 12. Affected embryos at embryonic day
10.5 have a neural-tube closure defect with ruffling of the neural fold ridges, a
yolk sac erythropoietic failure, and elevated alpha-ketoglutarate in the amniotic
fluid. We found that these animals have normal mitochondrial ribo- and
deoxyribonucleoside triphosphate levels, suggesting that transport of these
molecules is not the primary role of SLC25A19. We identified thiamine
pyrophosphate (ThPP) transport as a candidate function of SLC25A19 through
homology searching and confirmed it by using transport assays of the recombinant
reconstituted protein. The mitochondria of Slc25a19(-/-) and MCPHA cells have
undetectable and markedly reduced ThPP content, respectively. The reduction of
ThPP levels causes dysfunction of the alpha-ketoglutarate dehydrogenase complex,
which explains the high levels of this organic acid in MCPHA and suggests that
mitochondrial ThPP transport is important for CNS development.
PMID- 17035503
TI - IL-1 resets glucose homeostasis at central levels.
AB - Administration of IL-1beta results in a profound and long-lasting hypoglycemia.
Here, we show that this effect can be elicited by endogenous IL-1 and is related
to not only the capacity of the cytokine to increase glucose uptake in peripheral
tissues but also to mechanisms integrated in the brain. We show that (i) blockade
of IL-1 receptors in the brain partially counteracted IL-1-induced hypoglycemia;
(ii) peripheral administration or induction of IL-1 production resulted in IL
1beta gene expression in the hypothalamus of normal and insulin-resistant, leptin
receptor-deficient, diabetic db/db mice; (iii) IL-1-treated normal and db/db mice
challenged with glucose did not return to their initial glucose levels but
remained hypoglycemic for several hours. This effect was largely antagonized by
blockade of IL-1 receptors in the brain; and (iv) when animals with an advanced
Type II diabetes were treated with IL-1 and challenged with glucose, they died in
hypoglycemia. However, when IL-1 receptors in the brains of these diabetic mice
were blocked, they survived, and glucose blood levels approached those that these
mice had before IL-1 administration. The prolonged hypoglycemic effect of IL-1 is
insulin-independent and develops against increased levels of glucocorticoids,
catecholamines, and glucagon. These findings, together with the present
demonstration that this effect is integrated in the brain and is paralleled by IL
1beta expression in the hypothalamus, indicate that this cytokine can reset
glucose homeostasis at central levels. Such reset, along with the peripheral
actions of the cytokine, would favor glucose uptake by immune cells during
inflammatory/immune processes.
PMID- 17035504
TI - Sampling the multiple folding mechanisms of Trp-cage in explicit solvent.
AB - We investigate the kinetic pathways of folding and unfolding of the designed
miniprotein Trp- cage in explicit solvent. Straightforward molecular dynamics and
replica exchange methods both have severe convergence problems, whereas
transition path sampling allows us to sample unbiased dynamical pathways between
folded and unfolded states and leads to deeper understanding of the mechanisms of
(un)folding. In contrast to previous predictions employing an implicit solvent,
we find that Trp-cage folds primarily (80% of the paths) via a pathway forming
the tertiary contacts and the salt bridge, before helix formation. The remaining
20% of the paths occur in the opposite order, by first forming the helix. The
transition states of the rate-limiting steps are solvated native-like structures.
Water expulsion is found to be the last step upon folding for each route.
Committor analysis suggests that the dynamics of the solvent is not part of the
reaction coordinate. Nevertheless, during the transition, specific water
molecules are strongly bound and can play a structural role in the folding.
PMID- 17035505
TI - Chemical screening methods to identify ligands that promote protein stability,
protein crystallization, and structure determination.
AB - The 3D structures of human therapeutic targets are enabling for drug discovery.
However, their purification and crystallization remain rate determining. In
individual cases, ligands have been used to increase the success rate of protein
purification and crystallization, but the broad applicability of this approach is
unknown. We implemented two screening platforms, based on either fluorimetry or
static light scattering, to measure the increase in protein thermal stability
upon binding of a ligand without the need to monitor enzyme activity. In total,
221 different proteins from humans and human parasites were screened against one
or both of two sorts of small-molecule libraries. The first library comprised
different salts, pH conditions, and commonly found small molecules and was
applicable to all proteins. The second comprised compounds specific for protein
families of particular interest (e.g., protein kinases). In 20 cases, including
nine unique human protein kinases, a small molecule was identified that
stabilized the proteins and promoted structure determination. The methods are
cost-effective, can be implemented in any laboratory, promise to increase the
success rates of purifying and crystallizing human proteins significantly, and
identify new ligands for these proteins.
PMID- 17035506
TI - The distance that kinesin-1 holds its cargo from the microtubule surface measured
by fluorescence interference contrast microscopy.
AB - Kinesin-1 is a motor protein that carries cellular cargo such as membrane-bounded
organelles along microtubules (MTs). The homodimeric motor molecule contains two
N-terminal motor domains (the motor "heads"), a long coiled-coil domain (the
"rod" or "stalk"), and two small globular "tail" domains. Much has been learned
about how kinesin's heads step along a MT and how the tail is involved in cargo
binding and autoinhibition. However, little is known about the role of the rod.
Here, we investigate the extension of the rod during active transport by
measuring the height at which MTs glide over a kinesin-coated surface in the
presence of ATP. To perform height measurements with nanometer precision, we used
fluorescence interference contrast microscopy, which is based on the self
interference of fluorescent light from objects near a reflecting surface. Using
an in situ calibrating method, we determined that kinesin-1 molecules elevate
gliding MTs 17 +/- 2 nm (mean +/- SEM) above the surface. When varying the
composition of the surrounding nucleotides or removing the negatively charged
COOH termini of the MTs by subtilisin digestion, we found no significant changes
in the measured distance. Even though this distance is significantly shorter than
the contour length of the motor molecule ( approximately 60 nm), it may be
sufficient to prevent proteins bound to the MTs or prevent the organelles from
interfering with transport.
PMID- 17035507
TI - The effect of intensive lipid lowering on coronary atheroma and clinical outcome.
AB - The association between raised plasma cholesterol and cardiovascular risk is well
established, with consistent evidence associating LDL-cholesterol reduction with
a reduction in primary and secondary cardiovascular events. It is believed that
intensive lipid lowering may improve clinical outcomes further by acting to
stabilise plaque and preventing plaque progression, ultimately reducing plaque
vulnerability. However, it remains uncertain whether a continued clinical benefit
occurs with intensive lipid lowering or if there is a threshold level below which
no further benefit occurs.
PMID- 17035508
TI - Transcatheter closure of perimembranous ventricular septal defect: is the risk of
heart block too high a price?
AB - The late development of heart block in paediatric patients following device
closure of a perimembranous ventricular septal defect may be a cause for concern.
PMID- 17035509
TI - Antithrombotic treatment for peripheral arterial disease.
AB - CONTEXT: Patients with peripheral arterial disease (PAD) bear a substantial risk
for vascular events in the coronary, cerebral and peripheral circulations. In
addition, this disorder is associated with a systemic milieu characterised by
ongoing platelet activation and heightened thrombogenesis. OBJECTIVE: To
determine the optimal antithrombotic prophylaxis for patients with PAD. DATA
SOURCES: Using terms related to PAD and antithrombotic agents, we searched the
following databases for relevant articles: MEDLINE, EMBASE, the Cochrane Central
Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the
National Institutes of Health Clinical Trials Database, Web of Science, and the
International Pharmaceutical Abstracts Database (search dates: 1 January 1990 to
1 January 2007). Additional articles were identified from cardiovascular and
vascular surgery conference proceedings, bibliographies of review articles, and
personal files. STUDY SELECTION: We focused on randomised trials, systematic
reviews and consensus guidelines of antithrombotic therapies for PAD. DATA
EXTRACTION: Detailed study information was abstracted by each author working
independently. RESULTS: Multiple studies show that patients with PAD manifest
platelet hyperaggregability, increased levels of soluble platelet activation
markers, enhanced thrombin generation and altered fibrinolytic potential. Many of
these markers predict subsequent cardiovascular events. Available randomised
trials and meta-analyses show that most available antithrombotic agents prevent
major cardiovascular events and death in patients with PAD, including aspirin,
aspirin/dipyridamole, clopidogrel, ticlopidine, picotamide and oral
anticoagulants. CONCLUSIONS: Although the most favourable risk-benefit profile,
cost-effectiveness and overall evidence base supports aspirin in this setting, we
provide scenarios in which alternatives to aspirin should be considered.
PMID- 17035510
TI - Biocompatibility of septal defect closure devices.
AB - OBJECTIVE: Despite their clinical introduction 10 years ago, no human series on
the healing response to Amplatzer and Starflex devices in humans have been
reported yet. We sought to investigate the biocompatibility of Amplatzer and
Cardioseal/Starflex septal occluder devices in humans and compare the findings to
results in experimental animals. METHODS: The healing response of Amplatzer and
Cardioseal/Starflex septal occluder devices in humans (n = 12, follow-up periods
from 5 days to 4 years) and in experimental animals (n = 32, follow-up periods
from 4 days to 1 year) was studied using a uniform work up protocol. Histological
sections of paraffin-wax-embedded or methacrylate-embedded specimen and scanning
electron microscopy were used for biocompatibility screening. RESULTS:
Neoendothelialisation of all examined devices was complete after 3 months in
vivo. Protruding metal frame parts, like screw threads and spring arms, were
covered last. The initial deposition of fibrin and blood cells on the polyester
fabric was subsequently organised by ingrown fibroblastic cells. Loosely arranged
and poorly vascularised young granulation tissue was transformed time-dependently
into quiescent fibre-rich connective repair tissue poor of cellular and capillary
vessel components. Consistently, a mild chronic inflammatory response directed
against textile fibres of both types of implants characterised by lymphocytic
infiltration and multinucleated foreign body giant cells was observed equally in
human and animal explants. CONCLUSIONS: Systematic biocompatibility screening in
a series of explanted human septal occluder devices showed results corresponding
to findings in animal studies with regard to neoendothelialisation, cellular
organisation of initial thrombus and persisting immune response.
PMID- 17035511
TI - Pregnancy and the various forms of the Fontan circulation.
AB - The Fontan operation is performed on those with highly complex congenital heart
disease and has improved the survival and quality of life of such patients.
Inevitably there are late complications secondary to extensive surgery and long
term survival estimates are about 70% at 10 years and 60-63% at 15 years.
Pregnancy therefore requires careful prior consideration. However, the opinion
that that pregnancy is not advisable for the Fontan patient is somewhat
contentious and maybe an oversimplification of what is a highly emotive and
complex issue.
PMID- 17035512
TI - Diagnosis of Paracoccidioidomycosis by detection of antigen and antibody in
bronchoalveolar lavage fluids.
AB - Paracoccidioidomycosis (PCM) is a systemic infection caused by the fungus
Paracoccidioides brasiliensis and is believed to be the leading cause of fungal
pulmonary infection. In this study, we used an inhibition enzyme-linked
immunosorbent assay to diagnose pulmonary PCM based on the detection of 43-kDa
and 70-kDa molecules in bronchoalveolar lavage fluids. The results were compared
with results obtained by classical methods for antibody detection.
PMID- 17035513
TI - Multiplex assay for simultaneous measurement of antibodies to multiple Plasmodium
falciparum antigens.
AB - Antibodies to Plasmodium falciparum are classically measured using the enzyme
linked immunosorbent assay (ELISA). Although highly sensitive, this technique is
labor-intensive when large numbers of samples must be screened against multiple
antigens. The suspension array technology (SAT) might be an alterative to ELISA,
as it allows measurement of antibodies against multiple antigens simultaneously
with a small volume of sample. This study sought to adapt the new SAT multiplex
system for measuring antibodies against nine malarial vaccine candidate antigens,
including recombinant proteins from two variants of merozoite surface protein 1,
two variants of apical merozoite antigen 1, erythrocyte binding antigen 175,
merozoite surface protein 3, and peptides from the circumsporozoite protein, ring
erythrocyte surface antigen, and liver-stage antigen 1. Various concentrations of
the antigens were coupled to microspheres with different spectral addresses, and
plasma samples from Cameroonian adults were screened by SAT in mono- and
multiplex formats and by ELISA. Optimal amounts of protein required to perform
the SAT assay were 10- to 100-fold less than that needed for ELISA. Excellent
agreement was found between the single and multiplex formats (R > or = 0.96),
even when two variants of the same antigen were used. The multiplex assay was
rapid, reproducible, required less than 1 mul of plasma, and had a good
correlation with ELISA. Thus, SAT provides an important new tool for studying the
immune response to malaria rapidly and efficiently in large populations, even
when the amount of plasma available is limited, e.g., in studies of neonates or
finger-prick blood.
PMID- 17035514
TI - The National Institutes of Health Blueprint for Neuroscience Research.
PMID- 17035515
TI - Estrogen, menopause, and the aging brain: how basic neuroscience can inform
hormone therapy in women.
PMID- 17035516
TI - Disease-modifying pathways in neurodegeneration.
PMID- 17035517
TI - Developmental plasticity of inhibitory circuitry.
PMID- 17035518
TI - Cellular excitability and the regulation of functional neuronal identity: from
gene expression to neuromodulation.
PMID- 17035519
TI - Influencing and interpreting visual input: the role of a visual feedback system.
PMID- 17035520
TI - Addiction and arousal: alternative roles of hypothalamic peptides.
AB - The importance of the lateral hypothalamus in the regulation of reward and
motivation has long been recognized. However, the neuronal network involved in
such a hypothalamic regulation of reward remains essentially unknown. Recently,
hypocretin-containing neurons, a group of hypothalamic neurons known to be
associated with the stability of arousal, have emerged as important structures in
the control of brain reward function. This review summarizes a Mini-Symposium
presented at the 2006 Annual Meeting of the Society for Neuroscience.
PMID- 17035521
TI - Singing mice, songbirds, and more: models for FOXP2 function and dysfunction in
human speech and language.
AB - In 2001, a point mutation in the forkhead box P2 (FOXP2) coding sequence was
identified as the basis of an inherited speech and language disorder suffered by
members of the family known as "KE." This mini-symposium review focuses on recent
findings and research-in-progress, primarily from five laboratories. Each aims at
capitalizing on the FOXP2 discovery to build a neurobiological bridge between
molecule and phenotype. Below, we describe genetic through behavioral techniques
used currently to investigate FoxP2 in birds, rodents, and humans for discovery
of the neural bases of vocal learning and language.
PMID- 17035523
TI - Bombesin receptors as a novel anti-anxiety therapeutic target: BB1 receptor
actions on anxiety through alterations of serotonin activity.
AB - The effects of PD 176252 [3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)
cyclohexylmethyl]-2-methyl-2-[3-(nitro-phenyl)ureido]propionamide], a nonpeptide
bombesin (BB) BB1/BB2 receptor antagonist, were assessed in rats using several
ethologically relevant tests of anxiety. Consistent with a role for the bombesin
family of peptides in subserving anxiety behaviors, the antagonist increased
social interaction (3.75 and 7.5 mg/kg, i.p.), dose-dependently attenuated the
number of vocalizations emitted by guinea pig pups separated from their mother (1
30 mg/kg, i.p.), reduced latency to approach a palatable snack in an anxiogenic
(unfamiliar) environment, and reduced the fear-potentiated startle response (5
and 10 mg/kg, i.p., and 100-200 ng per rat, i.c.v.). When administered directly
to the dorsal raphe nucleus (DRN), PD 176252 (20-500 ng) increased social
interaction under aversive conditions, as did the 5-HT1A receptor agonist 8
hydroxy-2(di-n-propylamino)tetralin (50 ng). Furthermore, intra-DRN microinfusion
of the peptide antagonist (PD 176252) suppressed, whereas its agonist [neuromedin
B (NMB)-30] promoted, the in vivo release of 5-HT in the ventral hippocampus. In
parallel, the suppressed social interaction elicited by intra-DRN administration
of NMB was attenuated by a systemically administered 5-HT2C (but not 5-HT1A)
receptor antagonist. Together, these findings suggest that endogenous BB-like
peptides at the DRN evoke the release of 5-HT from the limbic nerve terminals
originating from the raphe, specifically at the ventral hippocampus, resulting in
anxiogenesis. The finding that this action was attenuated by BB receptor (BB1
and/or BB2) antagonists suggests that these compounds may represent a novel class
of anxiolytic agents.
PMID- 17035522
TI - Next-generation optical technologies for illuminating genetically targeted brain
circuits.
AB - Emerging technologies from optics, genetics, and bioengineering are being
combined for studies of intact neural circuits. The rapid progression of such
interdisciplinary "optogenetic" approaches has expanded capabilities for optical
imaging and genetic targeting of specific cell types. Here we explore key recent
advances that unite optical and genetic approaches, focusing on promising
techniques that either allow novel studies of neural dynamics and behavior or
provide fresh perspectives on classic model systems.
PMID- 17035524
TI - Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for
tRNA-charging enzymes in peripheral axons.
AB - Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy
type V (dSMA-V) are axonal neuropathies characterized by a phenotype that is more
severe in the upper extremities. We previously implicated mutations in the gene
encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V. GARS is
a member of the family of aminoacyl-tRNA synthetases responsible for charging
tRNA with cognate amino acids; GARS ligates glycine to tRNA(Gly). Here, we
present functional analyses of disease-associated GARS mutations and show that
there are not any significant mutation-associated changes in GARS expression
levels; that the majority of identified GARS mutations modeled in yeast severely
impair viability; and that, in most cases, mutant GARS protein mislocalizes in
neuronal cells. Indeed, four of the five mutations studied show loss-of-function
features in at least one assay, suggesting that tRNA-charging deficits play a
role in disease pathogenesis. Finally, we detected endogenous GARS-associated
granules in the neurite projections of cultured neurons and in the peripheral
nerve axons of normal human tissue. These data are particularly important in
light of the recent identification of CMT-associated mutations in another tRNA
synthetase gene [YARS (tyrosyl-tRNA synthetase gene)]. Together, these findings
suggest that tRNA-charging enzymes play a key role in maintaining peripheral
axons.
PMID- 17035525
TI - Oligomerization of KCC2 correlates with development of inhibitory
neurotransmission.
AB - The neuron-specific K+-Cl- cotransporter KCC2 extrudes Cl- and renders GABA and
glycine action hyperpolarizing. Thus, it plays a pivotal role in neuronal
inhibition. Development-dependent KCC2 activation is regulated at the
transcriptional level and by unknown posttranslational mechanisms. Here, we
analyzed KCC2 activation at the protein level in the developing rat lateral
superior olive (LSO), a prominent auditory brainstem structure. Electrophysiology
demonstrated ineffective KCC2-mediated Cl- extrusion in LSO neurons at postnatal
day 3 (P3). Immunohistochemical analyses by confocal and electron microscopy
revealed KCC2 signals at the plasma membrane in the somata and dendrites of both
immature and mature neurons. Biochemical analysis demonstrated mature
glycosylation pattern of KCC2 at both stages. Immunoblot analysis of the immature
brainstem demonstrated mainly monomeric KCC2. In contrast, three KCC2 oligomers
with molecular masses of approximately 270, approximately 400, and approximately
500 kDa were identified in the mature brainstem. These oligomers were sensitive
to sulfhydryl-reducing agents and resistant to SDS, contrary to the situation
seen in the related Na+-(K+)-Cl- cotransporter. In HEK-293 cells, coexpressed
hemagglutinin-tagged KCC2 assembled with histidine-tagged KCC2, demonstrating
formation of homomers. Based on these findings, we conclude that the oligomers
represent KCC2 dimers, trimers, and tetramers. Finally, immunoblot analysis
identified a development-dependent increase in the oligomer/monomer ratio from
embryonic day 18 to P30 throughout the brain that correlates with KCC2
activation. Together, our data indicate that the developmental shift from
depolarization to hyperpolarization can be determined by both increased gene
expression and KCC2 oligomerization.
PMID- 17035526
TI - Learning rules for spike timing-dependent plasticity depend on dendritic synapse
location.
AB - Previous studies focusing on the temporal rules governing changes in synaptic
strength during spike timing-dependent synaptic plasticity (STDP) have paid
little attention to the fact that synaptic inputs are distributed across complex
dendritic trees. During STDP, propagation of action potentials (APs) back to the
site of synaptic input is thought to trigger plasticity. However, in pyramidal
neurons, backpropagation of single APs is decremental, whereas high-frequency
bursts lead to generation of distal dendritic calcium spikes. This raises the
question whether STDP learning rules depend on synapse location and firing mode.
Here, we investigate this issue at synapses between layer 2/3 and layer 5
pyramidal neurons in somatosensory cortex. We find that low-frequency pairing of
single APs at positive times leads to a distance-dependent shift to long-term
depression (LTD) at distal inputs. At proximal sites, this LTD could be converted
to long-term potentiation (LTP) by dendritic depolarizations suprathreshold for
BAC-firing or by high-frequency AP bursts. During AP bursts, we observed a
progressive, distance-dependent shift in the timing requirements for induction of
LTP and LTD, such that distal synapses display novel timing rules: they
potentiate when inputs are activated after burst onset (negative timing) but
depress when activated before burst onset (positive timing). These findings could
be explained by distance-dependent differences in the underlying dendritic
voltage waveforms driving NMDA receptor activation during STDP induction. Our
results suggest that synapse location within the dendritic tree is a crucial
determinant of STDP, and that synapses undergo plasticity according to local
rather than global learning rules.
PMID- 17035527
TI - Intracellular zinc elevation measured with a "calcium-specific" indicator during
ischemia and reperfusion in rat hippocampus: a question on calcium overload.
AB - Much of our current evidence concerning of the role of calcium (Ca2+) as a second
messenger comes from its interaction with fluorescent probes; however, many Ca2+
probes also have a higher affinity for another divalent cation: zinc (Zn2+). In
this study, using a selective Zn2+ probe (Newport Green), we investigated the
accumulation of intracellular Zn2+ transients in acute rat hippocampal slices
during ischemia, simulated by oxygen and glucose deprivation (OGD). Subsequent
reperfusion with glucose-containing oxygenated medium resulted in an additional
increase in intracellular Zn2+. Such observations compelled us to investigate the
contribution of Zn2+ to the alleged intracellular Ca2+ overload occurring in
ischemia and reperfusion. Using confocal fluorescent microscopy of Calcium Green
1, a widely used Ca2+ indicator, we detected increases in fluorescence intensity
during OGD and reperfusion. However, application of a Zn2+ chelator, at the peak
of the fluorescence elevation (interpreted as Ca2+ overload), resulted in a
significant drop in intensity, suggesting that rising Zn2+ is the primary source
of the increasing Calcium Green-1 fluorescence. Finally, staining with the cell
viability indicator propidium iodide revealed that Zn2+ is responsible for the
ischemic neuronal cell death, because Zn2+ chelation prevented cells from
sustaining ischemic damage. Current cellular models of ischemic injury center on
Ca2+-mediated excitotoxicity. Our results indicate that Zn2+ elevation
contributes to conventionally recognized Ca2+ overload and also suggest that the
role of Ca2+ in neurotoxicity described previously using Ca2+ probes may need to
be re-examined to determine whether effect previously attributed to Ca2+ could,
in part, be attributable to Zn2+.
PMID- 17035528
TI - The transcription factor six1 inhibits neuronal and promotes hair cell fate in
the developing zebrafish (Danio rerio) inner ear.
AB - The developmental processes leading to the differentiation of mechanosensory hair
cells and statoacoustic ganglion neurons from the early otic epithelium remain
unclear. Possible candidates include members of the Pax-Six-Eya-Dach (paired box
sine oculis homeobox-eyes absent-dachshund) gene regulatory network. We cloned
zebrafish six1 and studied its function in inner ear development. Gain- and loss
of-function experiments show that six1 has opposing roles in hair cell and
neuronal lineages. It promotes hair cell fate and, conversely, inhibits neuronal
fate by differentially affecting cell proliferation and cell death in these
lineages. By independently targeting hair cells with atoh1a (atonal homolog 1a)
knockdown or neurons with neurog1 (neurogenin 1) knockdown, we showed that the
remaining cell population, neurons or hair cells, respectively, is still affected
by gain or loss of six1 function. six1 interacts with other members of the Pax
Six-Eya-Dach regulatory network, in particular dacha and dachb in the hair cell
but not neuronal lineage. Unlike in mouse, six1 does not appear to be dependent
on eya1, although it seems to be important for the regulation of eya1 and pax2b
expression in the ventral otic epithelium. Furthermore, six1 expression appears
to be regulated by pax2b and also by foxi1 (forkhead box I1) as expected for an
early inducer of the otic placode. Our results are the first to demonstrate a
dual role for a member of the Pax-Six-Eya-Dach regulatory network in inner ear
development.
PMID- 17035529
TI - A progressive and cell non-autonomous increase in striatal neural stem cells in
the Huntington's disease R6/2 mouse.
AB - Neural stem and progenitor cells are located in the subependyma of the adult
forebrain. An increase in adult subependymal cell proliferation is reported after
various kinds of brain injury. We demonstrate an expansion of neural precursor
cells in the postnatal subependyma in a murine genetic disease model of
Huntington's disease (HD), the R6/2 mouse. We used the in vitro neurosphere assay
as an index of the number of neural stem cells in vivo and to assess
proliferation kinetics in vitro and in vivo bromodeoxyuridine labeling to assess
the progenitor cell population and their fates. Disease progression in this model
leads to an increase in the numbers of neural stem cells in the adult striatal
subependyma. This increase is produced cell non-autonomously by events in the
R6/2 brains as the mice become increasingly symptomatic. Once the neural stem
cell increase is induced in vivo, it is maintained during in vitro passaging of
neural stem cells, but the neural stem cell increase is not reproduced during in
vitro passaging of neural stem cells from presymptomatic R6/2 mice. In addition,
we show that some of the R6/2 neural progenitor cells show a change from their
normal migration destiny toward the olfactory bulb. Instead, some of these cells
migrate into the striatum, one of the main affected areas in HD. Our findings
demonstrate that HD damage recruits precursor cells in two ways: expansion of
neural stem cells and altered migration of progenitor cells.
PMID- 17035530
TI - Different mechanisms exist for the plasticity of glutamate reuptake during early
long-term potentiation (LTP) and late LTP.
AB - Regulation of glutamate reuptake occurs along with several forms of synaptic
plasticity. These associations led to the hypothesis that regulation of glutamate
uptake is a general component of plasticity at glutamatergic synapses. We tested
this hypothesis by determining whether glutamate uptake is regulated during both
the early phases (E-LTP) and late phases (L-LTP) of long-term potentiation (LTP).
We found that glutamate uptake was rapidly increased within minutes after
induction of LTP and that the increase in glutamate uptake persisted for at least
3 h in CA1 of the hippocampus. NMDA receptor activation and Na+-dependent high
affinity glutamate transporters were responsible for the regulation of glutamate
uptake during all phases of LTP. However, different mechanisms appear to be
responsible for the increase in glutamate uptake during E-LTP and L-LTP. The
increase in glutamate uptake observed during E-LTP did not require new protein
synthesis, was mediated by PKC but not cAMP, and as previously shown was
attributable to EAAC1 (excitatory amino acid carrier-1), a neuronal glutamate
transporter. On the other hand, the increase in glutamate uptake during L-LTP
required new protein synthesis and was mediated by the cAMP-PKA (protein kinase
A) pathway, and it involved a different glutamate transporter, GLT1a (glutamate
transporter subtype 1a). The switch in mechanisms regulating glutamate uptake
between E-LTP and L-LTP paralleled the differences in the mechanisms responsible
for the induction of E-LTP and L-LTP. Moreover, the differences in signaling
pathways and transporters involved in regulating glutamate uptake during E-LTP
and L-LTP indicate that different functions and/or sites may exist for the
changes in glutamate uptake during E-LTP and L-LTP.
PMID- 17035531
TI - Adenosinergic mechanisms contribute to individual differences in sleep
deprivation-induced changes in neurobehavioral function and brain rhythmic
activity.
AB - Large individual differences characterize the changes induced by sleep
deprivation on neurobehavioral functions and rhythmic brain activity. To
investigate adenosinergic mechanisms in these differences, we studied the effects
of prolonged waking and the adenosine receptor antagonist caffeine on sustained
vigilant attention and regional electroencephalogram (EEG) power in the ranges of
theta activity (6.25-8.25 Hz) in waking and the slow oscillation (<1 Hz) in
sleep. Activity in these frequencies is functionally related to sleep
deprivation. In 12 subjectively caffeine-sensitive and 10 -insensitive young men,
psychomotor vigilance task (PVT) performance and EEG were assessed at 3 h
intervals before, during, and after one night without sleep. After 11 and 23 h
waking, subjects received 200 mg caffeine and placebo in double-blind, cross-over
manner. In the placebo condition, sleep deprivation impaired PVT speed more in
caffeine-sensitive than in caffeine-insensitive men. This difference was
counteracted by caffeine. Theta power in waking increased more in a frontal EEG
derivation than in a posterior derivation. Caffeine attenuated this power
gradient in caffeine sensitive subjects. Sleep loss also differently affected the
power distribution <1 Hz in non-rapid eye movement sleep between caffeine
sensitive and insensitive subjects. Also, this difference was mirrored by the
action of caffeine. The effects of sleep deprivation and caffeine on sustained
attention and regional EEG power in waking and sleep were inversely related.
These findings suggest that adenosinergic mechanisms contribute to individual
differences in waking-induced impairment of neurobehavioral performance and
functional aspects of EEG topography associated with sleep deprivation.
PMID- 17035532
TI - Acute impairment of mitochondrial trafficking by beta-amyloid peptides in
hippocampal neurons.
AB - Defects in axonal transport are often associated with a wide variety of
neurological diseases including Alzheimer's disease (AD). Beta-amyloid (Abeta) is
a major component of neuritic plaques associated with pathological conditions of
AD brains. Here, we report that a brief exposure of cultured hippocampal neurons
to Abeta molecules resulted in rapid and severe impairment of mitochondrial
transport without inducing apparent cell death and significant morphological
changes. Such acute inhibition of mitochondrial transport was not associated with
a disruption of mitochondria potential nor involved aberrant cytoskeletal
changes. Abeta also did not elicit significant Ca2+ signaling to affect
mitochondrial trafficking. However, stimulation of protein kinase A (PKA) by
forskolin, cAMP analogs, or neuropeptides effectively alleviated the impairment.
We also show that Abeta inhibited mitochondrial transport by acting through
glycogen synthase kinase 3beta (GSK3beta). Given that mitochondria are crucial
organelles for many cellular functions and survival, our findings thus identify
an important acute action of Abeta molecules on nerve cells that could
potentially contribute to various abnormalities of neuronal functions under AD
conditions. Manipulation of GSK3beta and PKA activities may represent a key
approach for preventing and alleviating Abeta cytotoxicity and AD pathological
conditions.
PMID- 17035533
TI - Chemokine fractalkine/CX3CL1 negatively modulates active glutamatergic synapses
in rat hippocampal neurons.
AB - We examined the effects of the chemokine fractalkine (CX3CL1) on EPSCs evoked by
electrical stimulation of Schaffer collaterals in patch-clamped CA1 pyramidal
neurons from rat hippocampal slices. Acute application of CX3CL1 caused a
sustained reduction of EPSC amplitude, with partial recovery after washout.
CX3CL1-induced EPSC depression is postsynaptic in nature, because paired-pulse
ratio was maintained, amplitude distribution of spontaneous excitatory
postsynaptic currents shifted to lower values, and whole-cell current responses
to AMPA were reversibly inhibited. EPSC depression by CX3CL1 is mediated by
CX3CL1 receptor (CX3CR1), because CX3CL1 was unable to influence EPSC amplitude
in CA1 pyramidal neurons from CX3CR1 knock-out mice. CX3CL1-induced depression of
both EPSC and AMPA current was not observed in the absence of afferent fiber
stimulation or AMPA receptor activation, respectively, indicating the requirement
of sustained receptor activity for its development. Findings obtained from
hippocampal slices, cultured hippocampal neurons, and transfected human embryonic
kidney cells indicate that a Ca2+-, cAMP-, and phosphatase-dependent process is
likely to modulate CX3CL1 effects because of the following: (1) CX3CL1-induced
depression was antagonized by intracellular BAPTA, 8Br-cAMP, phosphatase
inhibitors, and pertussis toxin (PTX); (2) CX3CL1 inhibited forskolin-induced
cAMP formation sensitive to PTX; and (3) CX3CL1 inhibited forskolin-induced
Ser845 GluR1 phosphorylation, which was sensitive to PTX and dependent on Ca2+
and phosphatase activity. Together, these findings indicate that CX3CL1
negatively modulates AMPA receptor function at active glutamatergic synapses
through cell-signaling pathways by influencing the balance between kinase and
phosphatase activity.
PMID- 17035534
TI - Deletion of annexin 2 light chain p11 in nociceptors causes deficits in
somatosensory coding and pain behavior.
AB - The S100 family protein p11 (S100A10, annexin 2 light chain) is involved in the
trafficking of the voltage-gated sodium channel Na(V)1.8, TWIK-related acid
sensitive K+ channel (TASK-1), the ligand-gated ion channels acid-sensing ion
channel 1a (ASIC1a) and transient receptor potential vanilloid 5/6 (TRPV5/V6), as
well as 5-hydroxytryptamine receptor 1B (5-HT1B), a G-protein-coupled receptor.
To evaluate the role of p11 in peripheral pain pathways, we generated a loxP
flanked (floxed) p11 mouse and used the Cre-loxP recombinase system to delete p11
exclusively from nociceptive primary sensory neurons in mice. p11-null neurons
showed deficits in the expression of Na(V)1.8, but not of annexin 2. Damage
sensing primary neurons from these animals show a reduced tetrodotoxin-resistant
sodium current density, consistent with a loss of membrane-associated Na(V)1.8.
Noxious coding in wide-dynamic-range neurons in the dorsal horn was markedly
compromised. Acute pain behavior was attenuated in certain models, but no
deficits in inflammatory pain were observed. A significant deficit in neuropathic
pain behavior was also apparent in the conditional-null mice. These results
confirm an important role for p11 in nociceptor function.
PMID- 17035535
TI - Olfactory discrimination learning increases the survival of adult-born neurons in
the olfactory bulb.
AB - In the olfactory bulb (OB), new neurons are added throughout life, forming an
integral part of the functioning circuit. Yet only some of them survive more than
a month. To determine whether this turnover depends on olfactory learning, we
examined the survival of adult newborn cells labeled with the cell division
marker BrdU, administered before learning in an olfactory discrimination task. We
report that discrimination learning increases the number of newborn neurons in
the adult OB by prolonging their survival. Simple exposure to the pair of
olfactory cues did not alter neurogenesis, indicating that the mere activation of
sensory inputs during the learning task was insufficient to alter neurogenesis.
The increase in cell survival after learning was not uniformly distributed
throughout angular sectors of coronal sections of the OB. Monitoring odor
activation maps using patterns of Zif268 immediate early gene expression revealed
that survival was greater in regions more activated by the non-reinforced
odorant. We conclude that sensory activation in a learning context not only
controls the total number of newborn neurons in the adult OB, but also refines
their precise location. Shaping the distribution of newborn neurons by
influencing their survival could optimize the olfactory information processing
required for odor discrimination.
PMID- 17035536
TI - Cystine/glutamate exchange modulates glutathione supply for neuroprotection from
oxidative stress and cell proliferation.
AB - The cystine/glutamate exchanger (xCT) provides intracellular cyst(e)ine for
production of glutathione, a major cellular antioxidant. Using xCT overexpression
and underexpression, we present evidence that xCT-dependent glutathione
production modulates both neuroprotection from oxidative stress and cell
proliferation. In embryonic and adult rat brain, xCT protein was enriched at the
CSF-brain barrier (i.e., meninges) and also expressed in the cortex, hippocampus,
striatum, and cerebellum. To examine the neuroprotective role of xCT, various non
neuronal cell types (astrocytes, meningeal cells, and peripheral fibroblasts)
were cocultured with immature cortical neurons and exposed to oxidative glutamate
toxicity, a model involving glutathione depletion. Cultured meningeal cells,
which naturally maintain high xCT expression, were more neuroprotective than
astrocytes. Selective xCT overexpression in astrocytes was sufficient to enhance
glutathione synthesis/release and confer potent glutathione-dependent
neuroprotection from oxidative stress. Moreover, normally nonprotective
fibroblasts could be re-engineered to be neuroprotective with ectopic xCT
overexpression indicating that xCT is a key step in the pathway to glutathione
synthesis. Conversely, astrocytes and meningeal cells derived from sut/sut mice
(xCT loss-of-function mutants) showed greatly reduced proliferation in culture
attributable to increased oxidative stress and thiol deficiency, because growth
could be rescued by the thiol-donor beta-mercaptoethanol. Strikingly, sut/sut
mice developed brain atrophy by early adulthood, exhibiting ventricular
enlargement, thinning of the cortex, and shrinkage of the striatum. Our results
indicate that xCT can provide neuroprotection by enhancing glutathione export
from non-neuronal cells such as astrocytes and meningeal cells. Furthermore, xCT
is critical for cell proliferation during development in vitro and possibly in
vivo.
PMID- 17035537
TI - Neuronal responses to object images in the macaque inferotemporal cortex at
different stimulus discrimination levels.
AB - We can discriminate visual objects at multiple levels, from coarse categorization
to individual identification. It is not known how the brain adapts to the varying
levels of discrimination required in different behavioral contexts. In the
present study, we investigated whether the stimulus selectivity of neuronal
responses in the monkey inferotemporal cortex, which is the final unimodal stage
in the ventral visual pathway, changes with the varying levels of discrimination
required for different task conditions. Responses of each inferotemporal cell to
the same set of nine object images were examined in two different task
conditions. The task alternated between coarse and fine discriminations in the
first experiment, and the rule alternated between categorization and individual
object identification in the second experiment. Despite these changes in the task
requirements and the resulting differences in the monkeys' behavior, we found
that the responses of inferotemporal cells were largely unchanged in both
experiments. Our results suggest that representation of object images in the
inferotemporal cortex is stable and rather insensitive to these kinds of shifts
in behavioral context. Neuronal adaptations to behavioral context may occur
downstream of the inferotemporal cortex.
PMID- 17035538
TI - p25/cyclin-dependent kinase 5 induces production and intraneuronal accumulation
of amyloid beta in vivo.
AB - Aberrant processing of the amyloid precursor protein (APP) and the subsequent
accumulation of amyloid beta (Abeta) peptide has been widely established as a
central event in Alzheimer's disease (AD) pathogenesis. The sequential cleavage
steps required for the generation of Abeta are well outlined; however, there is a
relative dearth of knowledge pertaining to signaling pathways and molecular
mechanisms that can modulate this process. Here, we demonstrate a novel role for
p25/cyclin-dependent kinase 5 (Cdk5) in regulating APP processing, Abeta peptide
generation, and intraneuronal Abeta accumulation in inducible p25 transgenic and
compound PD-APP transgenic mouse models that demonstrate deregulated Cdk5
activity and a neurodegenerative phenotype. Induction of p25 resulted in enhanced
forebrain Abeta levels before any evidence of neuropathology in these mice.
Intracellular Abeta accumulated in perinuclear regions and distended axons within
the forebrains of these mice. Evidence for modulations in axonal transport or
beta-site APP cleaving enzyme 1 protein levels and activity are presented as
mechanisms that may account for the Abeta accumulation caused by p25/Cdk5
deregulation. Collectively, these findings delineate a novel pathological
mechanism involving aberrant APP processing by p25/Cdk5 and have important
implications in AD pathogenesis.
PMID- 17035539
TI - A behavioral role for feature detection by sensory bursts.
AB - Brief episodes of high-frequency firing of sensory neurons, or bursts, occur in
many systems, including mammalian auditory and visual systems, and are believed
to signal the occurrence of particularly important stimulus features, i.e., to
function as feature detectors. However, the behavioral relevance of sensory
bursts has not been established in any system. Here, we show that bursts in an
identified auditory interneuron of crickets reliably signal salient stimulus
features and reliably predict behavioral responses. Our results thus demonstrate
the close link between sensory bursts and behavior.
PMID- 17035540
TI - Angular tuning bias of vibrissa-responsive cells in the paralemniscal pathway.
AB - One of the most salient features of primary vibrissal afferents is their
sensitivity to the direction in which the vibrissae move. Directional sensitivity
is also well conserved in brainstem, thalamic, and cortical neurons of the
lemniscal pathway, indicating that this property plays a key role in the
organization of the vibrissal system. Here, we show that directional tuning is
also a fundamental feature of second-order interpolaris neurons that give rise to
the paralemniscal pathway. Quantitative assessment of responses to vibrissa
deflection revealed an anisotropic organization of receptive fields with regard
to topography, response magnitude, and the degree of angular tuning. Responses
evoked by all vibrissae within the receptive field of each cell exhibited a high
consistency of direction preference, but a striking difference in angular tuning
preference was found among cells that reside in the rostral and caudal divisions
of the interpolaris nucleus. Although in caudal interpolaris vectors of angular
preference pointed in all directions, in rostral interpolaris virtually all
vectors pointed upward, revealing a strong preference for this direction. Control
experiments showed that the upward bias did not rely on a preferential
innervation of rostral cells by upwardly tuned primary vibrissa afferents, nor
did it rely on a direction-selective recruitment of feedforward inhibition. We
thus propose that the upward preference bias of rostral cells, which project to
the posterior group of the thalamus, emerges from use-dependent synaptic
processes that relate to the kinematics of whisking.
PMID- 17035541
TI - Alpha-synuclein expression modulates microglial activation phenotype.
AB - Recent Parkinson's disease research has focused on understanding the function of
the cytosolic protein, alpha-synuclein, and its contribution to disease
mechanisms. Within neurons, alpha-synuclein is hypothesized to have a role in
regulating synaptic plasticity, vesicle release, and trafficking. In contrast,
glial-expressed alpha-synuclein remains poorly described. Here, we examine the
consequence of a loss of alpha-synuclein expression on microglial activation.
Using a postnatal brain-derived culture system, we defined the phenotype of
microglia from wild-type and knock-out alpha-synuclein mice (Scna-/-). Scna-/-
microglia displayed a basally increased reactive phenotype compared with the wild
type cells and an exacerbated reactive phenotype after stimulation. They also
exhibited dramatic morphologic differences compared with wild-type, presenting as
large, ramified cells filled with vacuole-like structures. This corresponded with
increased protein levels of activation markers, CD68 and beta1 integrin, in the
Scna-/- cells. More importantly, Scna-/- microglia, after stimulation, secreted
elevated levels of proinflammatory cytokines, TNFalpha (tumor necrosis factor
alpha) and IL-6 (interleukin-6), compared with wild type. However, despite the
reactive phenotype, Scna-/- cells had impaired phagocytic ability. We demonstrate
for the first time that alpha-synuclein plays a critical role in modulating
microglial activation state. We suggest that altered microglial alpha-synuclein
expression will affect their phenotype as has already been demonstrated in
neurons. This has direct ramifications for the contribution of microglia to the
pathophysiology of disease, particularly in familial cases linked to altered
alpha-synuclein expression.
PMID- 17035542
TI - Implications of assist-as-needed robotic step training after a complete spinal
cord injury on intrinsic strategies of motor learning.
AB - Robotic training paradigms that enforce a fixed kinematic control might be
suboptimal for rehabilitative training because they abolish variability, an
intrinsic property of neuromuscular control (Jezernik et al., 2003). In the
present study we introduce "assist-as-needed" (AAN) robotic training paradigms
for rehabilitation of spinal cord injury subjects. To test the efficacy of these
robotic control strategies to teach spinal mice to step, we divided 27 adult
female Swiss-Webster mice randomly into three groups. Each group was trained
robotically by using one of three control strategies: a fixed training trajectory
(Fixed group), an AAN training paradigm without interlimb coordination (Band
group), and an AAN training paradigm with bilateral hindlimb coordination (Window
group). Beginning at 14 d after a complete midthoracic spinal cord transection,
the mice were trained daily (10 min/d, 5 d/week) to step on a treadmill 10 min
after the administration of quipazine (0.5 mg/kg), a serotonin agonist, for a
period of 6 weeks. During weekly performance evaluations, the mice trained with
the AAN window paradigm generally showed the highest level of recovery as
measured by the number, consistency, and periodicity of steps during the testing
sessions. In all three measurements there were no significant differences between
the Band and the Fixed training groups. These results indicate that the window
training approach, which includes loose alternating interlimb coordination, is
more effective than a fixed trajectory paradigm with rigid alternating interlimb
coordination or an AAN paradigm without any interlimb constraints in promoting
robust postinjury stepping behavior.
PMID- 17035543
TI - Cerebellar modulation of trigeminal reflex blinks: interpositus neurons.
AB - Because of its simplicity, blinking is a prominent model system in analysis of
adaptation and conditioning with the cerebellum. Nevertheless, data on the role
of the cerebellum in modulation of normal reflex blinks are limited. We
correlated the discharge of interpositus (IP) neurons with normal trigeminal
reflex blinks and blink adaptation in urethane-anesthetized rats. Two groups of
IP neurons responded to cornea stimulation. One group, pause neurons, showed a
long cessation of their tonic discharge beginning 6 ms before the end of lid
closure. The second group, burst neurons, exhibited a transient increase in
firing frequency at a constant interval after the cornea stimulus. The cessation
of pause neuron activity appeared to contribute to the termination of blinks. The
tonic discharge rate increased and the cessation of pause neuron activity was
delayed coincident with increased amplitude and duration of reflex blinks
produced by blink adaptation. There was a coincident increase in the amplitude
and duration of reflex blinks with increased tonic activity and delayed pause in
pause neurons treated with the GABA(A) antagonist, gabazine. Burst neurons did
not appear to modulate reflex blinks. Burst neuron discharge correlated neither
with blink characteristics normally nor with blink adaptation. These findings
indicated that pause neurons affect reflex blinks by providing a tonic excitatory
input to facial motoneurons during lid closure and then disfacilitating those
motoneurons to adjust the termination of lid closure. Burst neurons may play a
role in eyelid conditioning.
PMID- 17035544
TI - Dopaminergic control of sleep-wake states.
AB - Dopamine depletion is involved in the pathophysiology of Parkinson's disease,
whereas hyperdopaminergia may play a fundamental role in generating
endophenotypes associated with schizophrenia. Sleep disturbances are known to
occur in both schizophrenia and Parkinson's disease, suggesting that dopamine
plays a role in regulating the sleep-wake cycle. Here, we show that novelty
exposed hyperdopaminergic mice enter a novel awake state characterized by
spectral patterns of hippocampal local field potentials that resemble
electrophysiological activity observed during rapid-eye-movement (REM) sleep.
Treatment with haloperidol, a D2 dopamine receptor antagonist, reduces this
abnormal intrusion of REM-like activity during wakefulness. Conversely, mice
acutely depleted of dopamine enter a different novel awake state characterized by
spectral patterns of hippocampal local field potentials that resemble
electrophysiological activity observed during slow-wave sleep (SWS). This
dopamine-depleted state is marked by an apparent suppression of SWS and a
complete suppression of REM sleep. Treatment with D2 (but not D1) dopamine
receptor agonists recovers REM sleep in these mice. Altogether, these results
indicate that dopamine regulates the generation of sleep-wake states. We propose
that psychosis and the sleep disturbances experienced by Parkinsonian patients
result from dopamine-mediated disturbances of REM sleep.
PMID- 17035545
TI - Ubiquitous and temperature-dependent neural plasticity in hibernators.
AB - Hibernating mammals are remarkable for surviving near-freezing brain temperatures
and near cessation of neural activity for a week or more at a time. This extreme
physiological state is associated with dendritic and synaptic changes in
hippocampal neurons. Here, we investigate whether these changes are a ubiquitous
phenomenon throughout the brain that is driven by temperature. We
iontophoretically injected Lucifer yellow into several types of neurons in fixed
slices from hibernating ground squirrels. We analyzed neuronal microstructure
from animals at several stages of torpor at two different ambient temperatures,
and during the summer. We show that neuronal cell bodies, dendrites, and spines
from several cell types in hibernating ground squirrels retract on entry into
torpor, change little over the course of several days, and then regrow during the
2 h return to euthermia. Similar structural changes take place in neurons from
the hippocampus, cortex, and thalamus, suggesting a global phenomenon.
Investigation of neural microstructure from groups of animals hibernating at
different ambient temperatures revealed that there is a linear relationship
between neural retraction and minimum body temperature. Despite significant
temperature-dependent differences in extent of retraction during torpor, recovery
reaches the same final values of cell body area, dendritic arbor complexity, and
spine density. This study demonstrates large-scale and seemingly ubiquitous
neural plasticity in the ground squirrel brain during torpor. It also defines a
temperature-driven model of dramatic neural plasticity, which provides a unique
opportunity to explore mechanisms of large-scale regrowth in adult mammals, and
the effects of remodeling on learning and memory.
PMID- 17035546
TI - Important contribution of alpha-neurexins to Ca2+-triggered exocytosis of
secretory granules.
AB - Alpha-neurexins constitute a family of neuronal cell surface molecules that are
essential for efficient neurotransmission, because mice lacking two or all three
alpha-neurexin genes show a severe reduction of synaptic release. Although
analyses of alpha-neurexin knock-outs and transgenic rescue animals suggested an
involvement of voltage-dependent Ca2+ channels, it remained unclear whether alpha
neurexins have a general role in Ca2+-dependent exocytosis and how they may
affect Ca2+ channels. Here we show by membrane capacitance measurements from
melanotrophs in acute pituitary gland slices that release from endocrine cells is
diminished by >50% in adult alpha-neurexin double knock-out and newborn triple
knock-out mice. There is a reduction of the cell volume in mutant melanotrophs;
however, no ultrastructural changes in size or intracellular distribution of the
secretory granules were observed. Recordings of Ca2+ currents from melanotrophs,
transfected human embryonic kidney cells, and brainstem neurons reveal that alpha
neurexins do not affect the activation or inactivation properties of Ca2+
channels directly but may be responsible for coupling them to release-ready
vesicles and metabotropic receptors. Our data support a general and essential
role for alpha-neurexins in Ca2+-triggered exocytosis that is similarly important
for secretion from neurons and endocrine cells.
PMID- 17035547
TI - An inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in
a mouse model of neurodegenerative disease.
AB - Various studies suggest that proteolytic activity may be involved in a number of
neurodegenerative disorders, including stroke and seizure. In this report, we
examined the role of tryptic serine proteases, plasminogen activators (PAs), in
the evolution of a neurodegenerative disease. Transgenic mice overexpressing an
axonally secreted inhibitor of serine proteases (neuroserpin) were crossed with
mice characterized by a "dying-back" motor neuron disease [progressive motor
neuronopathy (pmn/pmn)]. Compared with pmn/pmn mice that showed an increase in PA
activity, double mutant mice had decreased PA activity in sciatic nerves and
spinal cord; their lifespan was increased by 50%, their motor behavior was
stabilized, and histological analysis revealed increased numbers of myelinated
axons and rescue of motoneuron number and size. This is the first report showing
that a class of serine proteases (PAs) may be involved in the pathogenesis of a
motor neuron disease and more specifically in axonal degeneration. Inhibiting
serine proteases could offer a new strategy for delaying these disorders.
PMID- 17035548
TI - Effects of transdermal testosterone application on the ovarian response to FSH in
poor responders undergoing assisted reproduction technique-a prospective,
randomized, double-blind study.
PMID- 17035549
TI - Development of a novel home sperm test - temperature range.
PMID- 17035550
TI - Development of a novel home sperm test - what are the limitations?
PMID- 17035551
TI - Remembering and appreciating Wayne S. Fenton.
PMID- 17035552
TI - Law & psychiatry: insanity, guilty minds, and psychiatric testimony.
AB - This column describes a recent Supreme Court case, Clark v. Arizona, in which an
adolescent who had schizophrenia was convicted of first-degree murder of a police
officer who he believed was a hostile space alien. The Arizona courts had
rejected his insanity defense as well as a second defense that he lacked the
required intent to commit the crime (mens rea) because his delusions interfered
with his knowing that the victim was a police officer. The Court ultimately
declined to overturn Arizona's rules regarding the insanity defense and mens rea.
However, the column highlights the points in Justice Souter's decision that may
have implications for any case involving mental health issues.
PMID- 17035553
TI - Innovations: child and adolescent psychiatry: measuring outcomes of real-world
youth psychotherapy: whom to ask and what to ask?
AB - To illustrate complexities in outcomes measurement for youths receiving community
based mental health services, this column presents data on 112 youths in publicly
funded, usual-care psychotherapy. Youths and their parents separately completed
standard measures of outcomes in three domains--symptoms, functioning, and family
environment--at baseline and at six months. The results indicate minimal
agreement between youths and parents on individual outcome domains and almost no
overlap for each informant (youth and parent) across multiple domains. These
findings are especially relevant because service providers are increasingly
required to demonstrate treatment effectiveness and monitor youths' progress. The
results highlight the complexities in measuring the impact of care and indicate
the need to develop more feasible methods to measure multidimensional outcomes.
PMID- 17035554
TI - Best practices: environmental and therapeutic issues in psychiatric hospital
design: toward best practices.
AB - The psychiatric hospital environment plays a significant, though often
underappreciated, role in patient and staff functioning. This column reviews the
literature on important environmental and therapeutic issues in psychiatric
hospital design. Research findings and clinical conjecture reported over the past
50 years indicate that intervening environmentally through clinically informed,
patient-centered design can improve functioning both among and between patients
and staff. This column identifies specific best practice considerations and
recommendations for designing inpatient psychiatric facilities and may serve as a
useful planning resource to those interested in adopting a patient-centered,
inclusive approach to design and treatment.
PMID- 17035555
TI - Personal accounts: lawyering, psychiatric treatment, and schizophrenia: a healing
interaction.
PMID- 17035556
TI - Employment barriers for persons with psychiatric disabilities: update of a report
for the President's Commission.
AB - A major public policy problem is the extremely low labor force participation of
people with severe mental illness coupled with their overrepresentation on the
public disability rolls. This situation is especially troubling given the
existence of evidence-based practices designed to return them to the labor force.
This article reviews research from the fields of disability, economics, health
care, and labor studies to describe the nature of barriers to paid work and
economic security for people with disabling mental disorders. These barriers
include low educational attainment, unfavorable labor market dynamics, low
productivity, lack of appropriate vocational and clinical services, labor force
discrimination, failure of protective legislation, work disincentives caused by
state and federal policies, poverty-level income, linkage of health care access
to disability beneficiary status, and ineffective work incentive programs. The
article concludes with a discussion of current policy initiatives in health care,
mental health, and disability. Recommendations for a comprehensive system of
services and supports to address multiple barriers are presented. These include
access to affordable health care, including mental health treatment and
prescription drug coverage; integrated clinical and vocational services; safe and
stable housing that is not threatened by changes in earned income; remedial and
postsecondary education and vocational training; benefits counseling and
financial literacy education; economic security through asset development; legal
aid for dealing with employment discrimination; peer support and self-help to
enhance vocational self-image and encourage labor force attachment; and active
involvement of U.S. business and employer communities.
PMID- 17035558
TI - A comparison of competitive employment outcomes for the clubhouse and PACT
models.
AB - OBJECTIVE: This study determined whether the clubhouse model of community support
and psychiatric rehabilitation can produce competitive employment outcomes that
are comparable or superior to those of the Program of Assertive Community
Treatment (PACT) model. METHODS: This longitudinal study followed a group of 170
individuals with severe mental illness who were randomly assigned either to the
experimental design, a clubhouse program (N=86), or to the control design, a PACT
team (N=84). Study participants were tracked for 30 months, and employment
outcome data were collected. RESULTS: After 30 months, 72 clubhouse and 76 PACT
participants remained active in the project. After 30 months, 74 percent of PACT
participants and 60 percent of clubhouse participants had been placed in at least
one job. The average clubhouse participant worked 21.8 weeks per job and earned
$7.38 per hour, whereas the average PACT participant worked 13.1 weeks per job
and earned $6.30 per hour. CONCLUSIONS: Participants from both the PACT and
clubhouse models achieved high employment levels, with no significant differences
in weekly employment or 30-month job placement rates over the course of the
study. During this time, clubhouse participants earned significantly higher wages
and remained competitively employed for significantly more weeks per job than
PACT participants.
PMID- 17035559
TI - Strategies for coping with cognitive impairments of clients in supported
employment.
AB - OBJECTIVE: This study evaluated the strategies used by employment specialists to
help clients in supported employment programs manage cognitive impairments that
interfered with obtaining and keeping jobs. METHODS: Twenty-five supported
employment specialists were surveyed to identify strategies they used to help
their clients cope with cognitive problems in the domains of attention,
psychomotor speed, memory, and problem solving. Then, 50 employment specialists
were surveyed to determine whether they used each of the different coping
strategies generated in the first part of the study. For each strategy used, they
rated how effective it was. RESULTS: Employment specialists reported using a
total of 76 different strategies for helping their clients cope with cognitive
difficulties. The specialists reported using an average of 48 different coping
strategies, which they rated on average as just below effective. Strategies for
dealing with attention problems were rated as more effective than strategies used
in the other three domains. The number of coping strategies that they reported
using was significantly correlated with the perceived effectiveness of the
strategies and the proportion of clients in their caseload who were working.
CONCLUSIONS: Supported employment specialists were actively involved in helping
clients cope with their cognitive impairments. Use of more strategies was
correlated with specialists' greater perceived effectiveness of the strategies
and with higher rates of working clients on their caseloads, although the reasons
for these associations are unclear. Further research is needed to evaluate
whether employment specialists' use of more strategies to help clients cope with
cognitive problems contributes to better work outcomes.
PMID- 17035557
TI - Supported employment outcomes of a randomized controlled trial of ACT and
clubhouse models.
AB - OBJECTIVE: In a randomized controlled trial, a vocationally integrated program of
assertive community treatment (ACT) was compared with a certified clubhouse in
the delivery of supported employment services. METHODS: Employment rates, total
work hours, and earnings for 121 adults with serious mental illness interested in
work were compared with published benchmark figures for exemplary supported
employment programs. The two programs were then compared on service engagement,
retention, and employment outcomes in regression analyses that controlled for
background characteristics, program preference, and vocational service receipt.
RESULTS: Outcomes for 63 ACT and 58 clubhouse participants met or exceeded most
published outcomes for specialized supported employment teams. Compared with the
clubhouse program, the ACT program had significantly (p<.05) better service
engagement (ACT, 98 percent; clubhouse, 74 percent) and retention (ACT, 79
percent; clubhouse, 58 percent) over 24 months, but there was no significant
difference in employment rates (ACT, 64 percent; clubhouse, 47 percent). Compared
with ACT participants, clubhouse participants worked significantly longer (median
of 199 days versus 98 days) for more total hours (median of 494 hours versus 234
hours) and earned more (median of $3,456 versus $1,252 total earnings). Better
work performance by clubhouse participants was partially attributable to higher
pay. CONCLUSIONS: Vocationally integrated ACT and certified clubhouses can
achieve employment outcomes similar to those of exemplary supported employment
teams. Certified clubhouses can effectively provide supported employment along
with other rehabilitative services, and the ACT program can ensure continuous
integration of supported employment with clinical care.
PMID- 17035560
TI - Increasing the utilization of supported employment services with the need for
change scale.
AB - OBJECTIVE: This study compared consumers' self-reports of felt need for
employment with their practitioners' assessments of need to determine whether
consumers' decisions to attend supported employment services and their acceptance
into supported employment services could be predicted. METHODS: In 2004 a group
of 147 unemployed service recipients from a region of the Connecticut Department
of Mental Health and Addiction Services rated their felt need for employment on
the Need for Change (NFC) scale. Correlations between felt need and their
decisions to accept supported employment services within the next six months were
determined. Correlations between their practitioners' independent decisions to
refer them to supported employment services and the consumers' decisions to
accept referrals were also determined. RESULTS: The consumers' decisions to
accept a referral had a correlation of .72 with their NFC ratings, compared with
.17 with their practitioners' decision to refer them. Of 49 people with high NFC
ratings (high felt need for employment), 45 were accepted into supported
employment services. Only ten of these consumers would have been referred by
their practitioners. The NFC increased referrals to supported employment by 24
percent in this sample. CONCLUSION: The NFC scale may be a valid tool for
referring consumers to supported employment services.
PMID- 17035562
TI - Commentary: policy priorities and shifting sands in the supported employment
evidence base.
PMID- 17035561
TI - Rates of unemployment and incidence of police-initiated examinations for
involuntary hospitalization in Florida.
AB - OBJECTIVE: This study tested the hypothesis that contraction of regional
economies affects the incidence of involuntary admissions to psychiatric
emergency services by reducing community tolerance for persons perceived as
threatening to others. METHODS: This hypothesis was tested with time-series
analyses of the relationship between initial claims for unemployment in Florida
between July 4, 1999, and June 28, 2003, and the weekly number of men and women
presented by police to be examined for involuntary psychiatric hospitalization
because of danger to others. The analyses controlled for admissions presented by
mental health professionals because of danger to others and for admissions
presented by police because of neglect or disability. RESULTS: When the analyses
controlled for autocorrelation and other covariates, claims for unemployment
insurance were significantly associated with the number of men presented by
police for danger to others. During the study period, police presented 5,897 men
for examination because of danger to others. Increased unemployment claims were
associated with approximately 309 more men being presented for examination than
expected from prior presentation rates and from the number presented by mental
health professionals for danger to others and by police for neglect or
disability. No such association was found for women. CONCLUSIONS: Consistent with
theory, this study found that presentations for involuntary admission to
psychiatric services increased after contractions in the labor market. Combining
the methods of this study with econometric forecasting may allow providers to
anticipate better the need for psychiatric services.
PMID- 17035563
TI - Randomized trial of a telephone care management program for outpatients starting
antidepressant treatment.
AB - OBJECTIVE: This study evaluated the effectiveness of a structured telephone-based
care management program for patients in a prepaid health plan receiving new
antidepressant prescriptions from psychiatrists. METHODS: Potential participants
were identified with computerized medical records and contacted by telephone.
Eligible and consenting participants were randomly assigned to continued usual
care (N=104) or to a three-session telephone care management program (N=103).
Care management contacts included assessment of depressive symptoms, medication
adherence, and medication side effects with structured feedback to treating
psychiatrists. Effectiveness was assessed three and six months after
randomization by blinded telephone assessments (depression scale on the Hopkins
Symptom Checklist [SCL] and patient-rated global improvement). Computerized
records were used to assess medication adherence and frequency of in-person
follow-up visits. RESULTS: Compared with usual care, the care management
intervention had no significant effect on the mean score of the SCL depression
scale at six months, on the probability of 50 percent improvement in depressive
symptoms (41 percent for care management and 37 percent for usual care), or on
the probability of patient-rated improvement (57 percent for care management and
52 percent for usual care). Patients assigned to care management made
significantly more medication management visits over six months (2.4 visits
compared with 2.0 visits; p=.035), but there were no significant differences in
rates of adequate medication treatment. CONCLUSIONS: This study found that a low
intensity telephone care management program did not appear to significantly
improve clinical outcomes for patients starting antidepressant treatment.
Compared with findings from earlier primary care studies, this study found that
patients receiving care from a psychiatrist received more intensive treatment,
although many still experienced poor outcomes.
PMID- 17035564
TI - Depression outcomes and quality of postdischarge care of elders hospitalized for
major depression.
AB - OBJECTIVES: Elders with depression are disproportionately hospitalized, and they
depend on postacute care for recovery. The authors hypothesized that higher
quality of postacute care would be associated with better depression outcomes for
older adults six months after discharge for inpatient psychiatric care. The study
also explored the time frame in which effects of quality of care on depression
outcomes were manifested. METHODS: The sample consisted of 148 elders (ages 60-95
years) who were hospitalized for major depression and discharged to their homes.
Quality of care was measured by the extent to which services met patients' needs.
Specifically, quality of care was assessed by whether four domains of needs
(psychiatric, medical, functional, and psychosocial) were met six weeks and six
months postdischarge. Depression outcomes at six months were measured by the
Geriatric Depression Scale. RESULTS: In bivariate analyses at six weeks, no
quality-of-care variables were associated with depression outcomes, but in
bivariate analyses at six months, quality of functional and psychosocial care was
related to depression outcomes. Multivariate analyses revealed that those whose
psychosocial needs were unmet at six months showed worse depression outcomes.
CONCLUSIONS: Findings provided partial support for the association between
quality of care and depression outcomes, in that quality of psychosocial care was
associated with better outcomes. Also, the findings suggest that the relationship
between quality of psychosocial care and depression outcomes may be evident after
six months of postacute care.
PMID- 17035565
TI - Reliability and validity of the substance abuse outcomes module.
AB - OBJECTIVE: The study sought to determine the validity and reliability of the
Substance Abuse Outcomes Module (SAOM), a self-report tool designed to assess
patient characteristics, process of care, and outcomes of care, using a minimum
amount of information, in order to improve treatment. METHODS: A longitudinal
field test (baseline and three-month follow-up) compared the SAOM to seven other
research instruments in the assessment of 100 substance-abusing patients who were
entering a new treatment episode. Quota samples of patients were drawn from two
private inpatient substance abuse treatment facilities and an outpatient
methadone clinic. The study's primary outcome measures were diagnostic accuracy,
internal and test-retest reliability of key constructs, concurrent and predictive
validity, and sensitivity to change. Cronbach's alpha coefficients were
calculated to examine internal consistency and reliability. Intraclass
correlation coefficients and kappa coefficients were used to examine test-retest
reliability. Concurrent validity of outcomes measures was examined with Pearson
or Spearman correlation coefficients and chi square and kappa statistics. Changes
between baseline and follow-up were examined as a function of case-mix measures
with ordinary least-squares multiple regression. Sensitivity to change was
examined by calculating effect size scores. RESULTS: The SAOM had high internal
consistency and a high level of agreement with research diagnoses at baseline and
follow-up. The SAOM was found to be highly reliable, to have very strong
validity, and to be sensitive to clinical change. CONCLUSIONS: The SAOM appears
to be a reasonably reliable and valid self-report instrument when used to monitor
substance abuse treatment among patients with a primary substance use diagnosis.
PMID- 17035566
TI - Statistical benchmarks for process measures of quality of care for mental and
substance use disorders.
AB - OBJECTIVE: Benchmarks, representing the level of performance achieved by the best
performing providers, can be used to set achievable goals for improving care, but
they have not heretofore been available for mental health care. This article
describes the application of a method for developing statistical benchmarks for
12 process measures of quality of care for mental and substance use disorders.
METHODS: Twelve quality measures--taken from a core measure set selected by a
multistakeholder panel through a formal consensus process--were constructed from
1994-1995 administrative data on care received by Medicaid beneficiaries in six
states. Conformance rates were calculated at the provider level and presented as
means, 90th-percentile results, and statistical benchmarks. Sample sizes for each
measure ranged from 356 to 4,494 providers and from 1,205 to 78,627 cases. Three
measures involved antidepressant treatment, two involved antipsychotic treatment,
and one involved mood stabilizers for bipolar disorder. Six other measures
involved follow-up treatment visits. RESULTS: Benchmarks for provider-level
performance ranged from 59.7 percent to 97.7 percent, markedly higher than the
mean results, which ranged from 9.4 percent to 65.4 percent. Benchmark results
varied widely-in contrast to results for these measures at the 90th percentile of
providers and in contrast to performance standards that apply the same numerical
goal across varied clinical processes. CONCLUSIONS: Statistical benchmarks can be
applied to results from quality assessment of mental health care. Further
research should examine whether incorporating benchmarks into quality improvement
activities leads to better mental health care and substance-related care and
improved outcomes.
PMID- 17035567
TI - Diagnosing psychotic disorders in the emergency department in the context of
substance use.
AB - OBJECTIVE: For patients who are actively using a substance and experience
psychotic symptoms, determining whether the psychotic symptoms are due to a
primary psychotic disorder or are substance induced is challenging, especially in
emergency departments, where historical information is limited. This study
examined the accuracy and subsequent treatment implications of emergency
department diagnoses among substance-using patients who were having their first
psychotic episode. METHODS: Emergency department diagnoses for 302 patients were
compared with best-estimate longitudinal diagnoses (BELDs) based on research
assessments at three time points (baseline, six months, and 12 months). RESULTS:
Of the 223 patients whose symptoms were diagnosed in the emergency department as
a primary psychotic disorder, one-quarter were determined by the BELD to have
substance-induced psychosis or no psychosis. Overall, the diagnostic agreement
was only fair (kappa=.32). Patients with an emergency department diagnosis of
primary psychosis were significantly more likely than those with an emergency
department diagnosis of substance-induced psychosis to be hospitalized, started
on antipsychotic medication, and referred to mental health services instead of
treatment for substance use (p<.001). Patients given an emergency department
diagnosis of primary psychosis who were found by the BELD to have substance
induced psychosis or no psychosis were significantly more likely to be treated
for a psychotic disorder rather than for substance-induced psychosis (p<.001)
CONCLUSIONS: Clinicians in psychiatric emergency departments appear to have a
tendency to attribute psychotic symptoms to a primary psychotic disorder rather
than to concurrent substance use. Given that the diagnosis has significant
implications for future management, it is important to improve diagnostic
approaches in the emergency department.
PMID- 17035568
TI - Mortality among discharged psychiatric patients in Florence, Italy.
AB - OBJECTIVE: Psychiatric disorders involve an increased risk of mortality. In Italy
psychiatric services are community based, and hospitalization is mostly reserved
for patients with acute illness. This study examined mortality risk in a cohort
of psychiatric inpatients for 16 years after hospital discharge to assess the
association of excess mortality from natural or unnatural causes with clinical
and sociodemographic variables and time from first admission. METHODS: At the end
of 2002 mortality and cause of death were determined for all patients (N=845) who
were admitted during 1987 to the eight psychiatric units active in Florence. The
mortality risk of psychiatric patients was compared with that of the general
population of the region of Tuscany by calculating standardized mortality ratios
(SMRs). Poisson multivariate analyses of the observed-to-expected ratio for
natural and unnatural deaths were conducted. RESULTS: The SMR for the sample of
psychiatric patients was threefold higher than that for the general population
(SMR=3.0; 95 percent confidence interval [CI]=2.7-3.4). Individuals younger than
45 years were at higher risk (SMR=11.0; 95 percent CI 8.0-14.9). The SMR for
deaths from natural causes was 2.6 (95 percent CI=2.3-2.9), and for deaths from
unnatural causes it was 13.0 (95 percent CI=10.1-13.6). For deaths from unnatural
causes, the mortality excess was primarily limited to the first years after the
first admission. For deaths from natural causes, excess mortality was more stable
during the follow-up period. CONCLUSIONS: Prevention of deaths from unnatural
causes among psychiatric patients may require promotion of earlier follow-up
after discharge. Improving prevention and treatment of somatic diseases of
psychiatric patients is important to reduce excess mortality from natural causes.
PMID- 17035569
TI - Mortality and medical comorbidity among patients with serious mental illness.
AB - OBJECTIVES: This study examined mortality and medical comorbidity among patients
with serious mental illness in Ohio. METHODS: Data for 20,018 patients admitted
to an Ohio public mental health hospital between 1998 and 2002 were matched
against state death records, and 608 deaths were identified. Leading causes of
death and medical comorbidities, years of potential life lost (YPLL), and
standardized mortality ratios were calculated for this population. RESULTS: Heart
disease (126 persons, or 21 percent) and suicides (108 persons, or 18 percent)
were the leading causes of death. The mean+/-SD number of YPLL was 32.0+/-12.6
years. The highest cause-specific mean YPLL was for suicides (41.7+/-10.3 years).
Deaths from unnatural causes had higher mean YPLL than deaths from any other
causes. Cause-specific mean YPLL were higher for women than for men, except for
homicides, pneumonia and influenza, and heart disease. The aggregated
standardized mortality ratio from all causes of death was 3.2, corresponding to
417 excess deaths (p<.001). Obesity (144 persons, or 24 percent) and hypertension
(136 persons, or 22 percent) were the most prevalent medical comorbidities.
CONCLUSIONS: This study demonstrated excess mortality among patients in Ohio with
serious mental illness. Results highlight the need to integrate delivery of
currently fragmented mental and physical health services and to target
interventions that improve quality-of-life outcomes for this population.
PMID- 17035570
TI - An update on affirmative businesses or social firms for people with mental
illness.
AB - Social firms, or "affirmative businesses" as they are known in North America, are
businesses created to employ people with disabilities and to provide a needed
product or service. This Open Forum offers an overview of the development and
status of social firms. The model was developed in Italy in the 1970s for people
with psychiatric disabilities and has gained prominence in Europe. Principles
include that over a third of employees are people with a disability or labor
market disadvantage, every worker is paid a fair-market wage, and the business
operates without subsidy. Independent of European influence, affirmative
businesses also have developed in Canada, the United States, Japan, and
elsewhere. The success of individual social firms is enhanced by locating the
right market niche, selecting labor-intensive products, having a public
orientation for the business, and having links with treatment services. The
growth of the social firm movement is aided by legislation that supports the
businesses, policies that favor employment of people with disabilities, and
support entities that facilitate technology transfer. Social firms can empower
individual employees, foster a sense of community in the workplace, and enhance
worker commitment through the organization's social mission.
PMID- 17035571
TI - Impact of consumer-operated services on empowerment and recovery of people with
psychiatric disabilities.
AB - OBJECTIVE: Although the professional literature is replete with descriptions of
consumer-operated services, empirical examination of these services has been
relatively limited. In this study, the cross-sectional relationship between
participation in consumer-operated services and measures of recovery and
empowerment is examined. METHODS: A total of 1,824 people with psychiatric
disability indicated whether they had participated in a peer support program (the
proxy of consumer-operated services) during the past four months. They also were
administered two five-factor measures of recovery and of empowerment. RESULTS:
Participation in peer support was associated with nine of ten factors generated
by the recovery and empowerment instruments. These associations remained
significant when commensurate demographic variables were controlled for.
CONCLUSIONS: Participation in peer support showed a significant association with
multiple outcome and recovery subscales, but the magnitude of the effect was
small. The associative nature of the data precludes stating that peer support
caused the observed improvement.
PMID- 17035572
TI - Effectiveness of a collaborative recovery training program in Australia in
promoting positive views about recovery.
AB - OBJECTIVE: This study examined the impact of a two-day, recovery-based training
program for mental health workers on knowledge, attitudes, and hopefulness
related to the recovery prospects of people with enduring mental illness.
METHODS: A self-report pre-post training repeated-measures design was used with
248 mental health workers from the community-based government health sector
(N=147) and nongovernment organizations (N= 101) in eastern Australia. RESULTS:
Staff attitudes and hopefulness improved after training. Trainees significantly
increased their knowledge regarding principles of recovery and belief in the
effectiveness of collaboration and consumer autonomy support, motivation
enhancement, needs assessment, goal striving, and homework use. CONCLUSIONS: This
preliminary evidence indicates that staff recovery orientation can improve with
minimal training.
PMID- 17035573
TI - State psychiatric hospital census after the 1999 Olmstead Decision: evidence of
decelerating deinstitutionalization.
AB - OBJECTIVE: The Supreme Court ruled in the 1999 Olmstead decision that
"unjustified isolation" of individuals with disabilities in institutions is a
violation of the Americans With Disabilities Act. This study examined the extent
to which state psychiatric hospital census across the United States has changed
significantly post-Olmstead. METHODS: Twenty years of national state hospital
census data (1984-2003) were used to assess trends in the rate of declines from
pre- to post-Olmstead periods. Data were organized into five four-year periods.
RESULTS: Steady declines in the hospital census nationally were found over all
periods, with especially large decreases in the 1990s. However, when the percent
change in hospital census in the two periods immediately before the Olmstead
decision (between 1992-1995 and 1996-1999) were compared with the percent change
in the periods immediately before and immediately after the Olmstead decision
(between 1996-1999 and 2000-2003), an 8 percent decrease in the magnitude of
decline was seen. CONCLUSIONS: State hospital census continues to decline but has
slowed significantly during the post-Olmstead period. More study of the factors
associated with this decline is needed.
PMID- 17035574
TI - Gender- and trauma-related predictors of use of mental health treatment services
among primary care patients.
AB - OBJECTIVE: Use of mental health care was investigated as a function of gender,
traumatic event frequency, posttraumatic stress disorder (PTSD), and attitudes
toward treatment among 194 primary care patients. METHODS: Patients were
recruited from primary care clinics, administered the Stressful Life Events
Screening Questionnaire, PTSD Symptom Scale, Attitudes Toward Seeking
Professional Psychological Help-Short Form, and a survey on use of services.
RESULTS: Lifetime mental health treatment was related to increased frequency of
traumatic events, positive attitudes toward treatment, and probable PTSD. Recent
use of mental health care and intensity of use were related to female gender and
greater frequency of trauma. Regression models yielded significant associations
for trauma frequency, positive treatment attitudes, and female gender. Trauma and
PTSD were associated with use more than gender and treatment attitudes were.
CONCLUSIONS: Use of and adherence to treatment may be improved by targeting
attitudes toward treatment.
PMID- 17035576
TI - Recovery-oriented care.
PMID- 17035577
TI - Malignant criminalization: from hypothesis to theory.
PMID- 17035578
TI - Community reintegration of prisoners with mental illness.
PMID- 17035582
TI - "Antipsychiatry" and "consumerism": perspectives and definitions.
PMID- 17035584
TI - The cost of low-demand housing programs.
PMID- 17035585
TI - Multiple sclerosis, mental illness, and forced treatment.
PMID- 17035586
TI - Legal consequences of seclusion and restraint.
PMID- 17035588
TI - MS does not damage the brain; serious mental illnesses do.
PMID- 17035589
TI - Successful use of VNS for depression.
PMID- 17035590
TI - Imagining the ecotrienes: a helpful new class of peptides.
PMID- 17035591
TI - Psychiatric effects of heat waves.
PMID- 17035592
TI - Providing jail diversion for people with mental illness.
PMID- 17035593
TI - Pursuing perfect depression care.
PMID- 17035594
TI - Providing recovery-based treatment to enhance quality of life.
PMID- 17035595
TI - Cellular retinoic acid bioavailability determines epithelial integrity: Role of
retinoic acid receptor alpha agonists in colitis.
AB - The epithelial barrier is determined primarily by intercellular tight junctions
(TJs). We have demonstrated previously that all-trans retinoic acid (atRA) plays
an important role in forming functional TJs through a specific retinoic acid
receptor (RAR)/retinoid X receptor heterodimer in epithelial cells. However, the
physiological relevance of retinoic acids (RAs) in maintaining the epithelial
integrity remains to be examined. Here, we show that several types of RA,
including atRA, promote the barrier function of epithelial TJs. Conversely, RA
depletion in the cells by overexpressing CYP26s, cytochrome P450 enzymes
specifically involved in the metabolic inactivation of RAs, induces an increase
of permeability as measured by two differently sized tracer molecules, inulin and
mannitol. This RA-mediated enhancement of barrier function is potentially
associated with the increased expression of TJ-associated genes such as occludin,
claudin-1, claudin-4, and zonula occludens-1. We also found that RARalpha is a
preferential regulator of the epithelial barrier in vitro. Studies of murine
experimental colitis, which is characterized by increased gut permeability,
reveal that RARalpha stimulation significantly attenuates the loss of the
epithelial barrier during colitis in vivo. Our results suggest that cellular RA
bioavailability determines the epithelial integrity, because it is a critical
regulator for barrier protection during mucosal injuries.
PMID- 17035596
TI - Estrogen receptor antagonist fulvestrant (ICI 182,780) inhibits the anti
inflammatory effect of glucocorticoids.
AB - The glucocorticoid receptor (GR) and estrogen receptor (ER) play important roles
in both physiological and pathological conditions involving cell growth and
differentiation, lipolysis, control of glucose metabolism, immunity, and
inflammation. In fact, recent studies suggest that 17beta-estradiol, like
glucocorticoids, may also have anti-inflammatory properties, even if the
molecular mechanisms responsible for these activities have not yet been
completely clarified. The present study was designed to gain a better
understanding of the possible cross-talk between GR and ER in a model of lung
inflammation (carrageenan-induced pleurisy). In particular, we have investigated
whether fulvestrant (ICI 182,780), a selective ER-alpha antagonist, is able to
attenuate the well known anti-inflammatory effect of dexamethasone (DEX), a
synthetic glucocorticoid, in ovariectomized rats. We show that ICI 182,780, a
selective ER-alpha antagonist, reverses the anti-inflammatory activity exhibited
by DEX. Moreover, the coadministration of ICI 182,780 significantly inhibited the
ability of DEX to reduce: 1) the degree of lung injury, 2) the rise in
myeloperoxidase activity, 3) the increase of poly-(ADP-ribose) polymerase
activity, tumor necrosis factor alpha, and interleukin-1beta levels, 4) inducible
nitric-oxide synthase, 5) lipid peroxidation, 6) nitrotyrosine formation, 7)
cyclooxygenase expression, and 8) the IkappaB-alpha degradation caused by
carrageenan administration. In addition, quantitative PCR shows that DEX down
regulates GR and up-regulates glucocorticoid-induced leucine zipper levels,
whereas ICI 182,780 does not counteract these effects. In conclusion, these
results suggest that the in vivo anti-inflammatory property of DEX is also
related to the ER-alpha.
PMID- 17035597
TI - Down-regulation of inhibitor of apoptosis proteins by deguelin selectively
induces apoptosis in breast cancer cells.
AB - The identification of differentially regulated apoptotic signals in normal and
tumor cells allows the development of cancer cell-selective therapies. Increasing
evidence shows that the inhibitor of apoptosis (IAP) proteins survivin and XIAP
are highly expressed in tumor cells but are absent or have very low levels of
expression in normal adult tissues. We found that inhibiting AKT activity with 10
to 100 nM deguelin, a small molecule derived from natural products, markedly
reduced the levels of both survivin and XIAP, inducing apoptosis in human breast
cancer cells but not in normal cells. It is noteworthy that we detected an
elevated level of cleaved poly(ADP-ribose) polymerase, a signature of caspase
activation, without a significant increase in caspase activity in deguelin
treated cancer cells. Our results suggest that severe down-regulation of the IAPs
by deguelin releases their inhibitory activity over pre-existing active caspases
present in cancer cells, inducing apoptosis without the need for further caspase
activation. Because normal cells have very low levels of p-AKT, XIAP, survivin,
and pre-existing caspase activity, deguelin had little effect on those cells. In
addition, we found that combining deguelin with chemotherapy drugs enhanced drug
induced apoptosis selectively in human tumor cells, which suggests that deguelin
has great potential for chemosensitization and could represent a new therapeutic
agent for treatment of breast cancer.
PMID- 17035599
TI - An evaluation of the cytochrome p450 inhibition potential of lisdexamfetamine in
human liver microsomes.
AB - The human cytochrome P450 (P450) system is implicated in many drug interactions.
Lisdexamfetamine dimesylate (NRP104), the proposed generic name for a new agent
under investigation for treatment of attention deficit hyperactivity disorder,
was recently analyzed for inhibitory drug-drug interactions with seven major P450
isoforms using pooled human liver microsomes. Probe substrates were used near the
K(m) concentration values reported in the literature for CYP1A2 (phenacetin),
CYP2A6 (coumarin), CYP2B6 (bupropion), CYP2C9 (tolbutamide), CYP2C19 ([S]
mephenytoin), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam and testosterone),
and lisdexamfetamine was evaluated at concentrations ranging from 0.01 to 100 muM
for its ability to inhibit the activity of these seven P450 isoforms. NADPH was
added to one set of samples to initiate metabolic reactions, which were then
terminated by adding organic solvent, vortexing the samples, and placing them on
ice. The relevant substrates were then introduced to both sets of samples so that
the percentage of remaining activity could be measured and compared. In addition,
these samples were compared with other samples with the same concentrations of
lisdexamfetamine but without preincubation. None of the seven P450 isoforms
showed any concentration-dependent inhibition. Comparison of results from
microsomes preincubated with and without NADPH showed no mechanism-based
inhibition. Neither concentration-dependent nor mechanism-based inhibition caused
by time-dependent inactivation of human P450 isoforms was shown for
lisdexamfetamine during in vitro testing. The evidence suggests that
lisdexamfetamine has a low potential for drug-drug interactions or initiation of
drug-drug interactions.
PMID- 17035598
TI - A new CYP3A5 variant, CYP3A5*11, is shown to be defective in nifedipine
metabolism in a recombinant cDNA expression system.
AB - A new CYP3A5 variant, CYP3A5*11, was found in a white European subject by DNA
sequencing. The CYP3A5*11 allele contains a single nucleotide polymorphism (SNP)
(g.3775A>G) in exon 2, which results in a Tyr53Cys substitution, and a g.6986A>G
splice change, the latter SNP previously reported in the defective CYP3A5*3
allele. However, the CYP3A5*3 is not a null allele because this variant is
associated with leaky splicing, resulting in small amounts of functional protein
still being produced. Therefore, we constructed a cDNA coding for the newly
identified CYP3A5.11 protein by site-directed mutagenesis, expressed it in
Escherichia coli, and partially purified it. Whereas bacteria transformed with
wild-type CYP3A5*1 cDNA expressed predominantly cytochrome P450 (P450), those
transfected with CYP3A5*11 expressed a significant amount of denatured cytochrome
P420 in addition to P450, suggesting the protein to be unstable. CYP3A5.11
exhibited a 38% decrease in the V(max) for nifedipine metabolism, a 2.7-fold
increase in the K(m), and a 4.4-fold decrease in the CL(int) of nifedipine
compared with CYP3A5.1. A polymerase chain reaction-restriction fragment length
polymorphism genotyping procedure was developed and used to genotype DNA of 500
white individuals for CYP3A5*11. No additional examples of this allele were
identified. In summary, individuals carrying the rare CYP3A5*11 allele are
predicted to have lower metabolism of CYP3A5 substrates than individuals
expressing CYP3A5*3.
PMID- 17035600
TI - Pregnane X receptor-dependent induction of the CYP3A4 gene by o,p'-1,1,1,
trichloro-2,2-bis (p-chlorophenyl)ethane.
AB - CYP3A4, the predominant cytochrome P450 (P450) expressed in human liver and
intestine, contributes to the metabolism of approximately half the drugs in
clinical use today. CYP3A4 catalyzes the 6beta-hydroxylation of a number of
steroid hormones and is involved in the bioactivation of environmental
procarcinogens. The expression of CYP3A4 is affected by several stimuli,
including environmental factors such as insecticides and pesticides. The o,p'
1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane (DDT) isomer of DDT comprises
approximately 20% of technical grade DDT, which is an organochloride pesticide.
We have recently shown that o,p'-DDT exposure increases CYP3A4 mRNA levels in
HepG2 cells. To determine the mechanism by which o,p'-DDT induces CYP3A4
expression, transactivation and electrophoretic mobility shift assays were
carried out, revealing that o,p'-DDT activates the CYP3A4 gene promoter through
the pregnane X receptor (PXR). CYP3A4 gene promoter activation resulted in both
an increase in CYP3A4 mRNA levels and an increase in the total CYP3A4 activity in
HepG2 cells. We also observed induction of CYP3A4 and mouse Cyp3a11 mRNA in the
intestine of CYP3A4-transgenic mice after exposure to 1 mg/kg o,p'-DDT. At higher
doses, a decrease of CYP3A4 inducibility was observed together with an increase
in levels of interleukin 6 mRNA, a proinflammatory cytokine that strongly
represses CYP3A4 transcription. The present study indicates that regulation of
other genes under PXR control may be altered by o,p'-DDT exposure.
PMID- 17035601
TI - A real-time fluorescence assay for measuring N-dealkylation.
AB - A real-time fluorescence assay system using a series of 9-N-(alkylamino)acridine
derivatives (methyl, ethyl, n-propyl, n-butyl, n-pentyl, and benzyl) that are N
dealkylated to 9-aminoacridine (9AA) is described. The product, 9AA, is
approximately 27-fold more fluorescent than the substrates using excitation and
emission wavelengths of 405 and 455 nm, respectively. Tests using expressed
CYP1A1, 1A2, 3A4, 3A5, 1B1, 2C9, 2C19, and 2D6 indicated that N-dealkylase
activity is specific for CYP1A1 and CYP2D6. CYP2D6 N-dealkylated methyl, ethyl, n
propyl, and n-butyl substrates, whereas CYP1A1 N-dealkylated these plus the n
pentyl derivative. Activities using 5 microM 9-N-(alkylamino)acridine substrates
ranged from 0.1 to 0.9 pmol 9AA/min/pmol P450. Kinetic constants for CYP1A1 N
dealkylation of the 9-N-(methylamino)acridine (MAA) and 9-N-(ethylamino)acridine
(EAA) were K(m) 1.09 +/- 0.68 and 0.35 +/- 0.21 microM and the V(max) 61.9 +/-
48.5 and 113.8 +/- 8.4 pmol 9AA/min/pmol CYP1A1, respectively. Kinetic constants
for CYP2D6 N-dealkylation of MAA and EAA were K(m) 7.9 +/- 5.4 and 3.2 +/- 1.6
microM, and V(max) 501 +/- 35.4 and 702.7 +/- 257 pmol 9AA/min/pmol CYP2D6,
respectively. The experimental binding energies (DeltaG(bind)) were calculated
for MAA with CYP1A1 and CYP2D6 to be -8.266 and -7.074 kcal/mol, respectively.
The DeltaG(bind) values for EAA with CYP1A1 and CYP2D6 were -8.950 and -7.618
kcal/mol, respectively. The substrates were suitable for monitoring N-dealkylase
activity in microsomal preparations (human, rat, and monkey hepatic preparations)
and human hepatocellular carcinoma cell suspensions. Assays were conducted by
monitoring reactions either in 96-well microtiter plates using a fluorescence
plate reader or in cuvettes using a spectrofluorimeter.
PMID- 17035602
TI - Cellular localization studies on human estrogen sulfotransferase SULT1E1 in human
embryonic kidney 293 cells.
AB - Human cytosolic sulfotransferase SULT1E1 catalyzes the sulfation of endogenous
estrogens as well as xenobiotic estrogen-like chemicals. This reaction increases
the water solubility of the molecule, which may affect its cellular distribution
and biological activity. This could alter estrogen signaling to the estrogen
receptor in human estrogen receptor-positive cells. The current work
characterized the cellular distribution of SULT1E1 in the human embryonic kidney
293 (HEK293) cell line using green fluorescent protein (GFP) tagging and
immunochemistry methods. The GFP-tagged recombinant SULT1E1 protein was expressed
and localized in the cytoplasm of HEK293 cells. By using a commercial anti
SULT1E1 peptide antibody, a 35.7-kDa protein was detected in HEK293 cells via
Western blot. The molecular mass of the protein detected suggested that it may be
related to native SULT1E1 protein. However, reverse transcription-polymerase
chain reaction (RT-PCR) with gene-specific primers could not confirm the presence
of the SULT1E1 transcript in the total RNA sample of HEK293 cells. The
discrepancy between protein and transcript data could be due to the instability
of SULT1E1 mRNA or the specificity of the anti-SULT1E1 antibody used. In the
present work, RT-PCR analysis with gene-specific primers also identified a
transcript fragment of human estrogen-related receptor gamma. Future studies on
the functional relationship between estrogen-related receptors and
sulfotransferases are expected to provide additional insights into the
physiological and toxicological roles of human estrogen sulfotransferases.
PMID- 17035603
TI - An emerging role for relaxin as a renal vasodilator.
PMID- 17035604
TI - Cyst number but not the rate of cystic growth is associated with the mutated gene
in autosomal dominant polycystic kidney disease.
AB - Data from serial renal magnetic resonance imaging of the Consortium of Radiologic
Imaging Study of PKD (CRISP) autosomal dominant polycystic kidney disease (PKD)
population showed that cystic expansion occurs at a consistent rate per
individual, although it is heterogeneous in the population, and that larger
kidneys are associated with more rapid disease progression. The significance of
gene type to disease progression is analyzed in this study of the CRISP cohort.
Gene type was determined in 183 families (219 cases); 156 (85.2%) had PKD1, and
27 (14.8%) had PKD2. PKD1 kidneys were significantly larger, but the rate of
cystic growth (PKD1 5.68%/yr; PKD2 4.82%/yr) was not different (P = 0.24). Cyst
number increased with age, and more cysts were detected in PKD1 kidneys (P <
0.0001). PKD1 is more severe because more cysts develop earlier, not because they
grow faster, implicating the disease gene in cyst initiation but not expansion.
These insights will inform the development of targeted therapies in autosomal
dominant PKD.
PMID- 17035605
TI - Chronic kidney disease progression.
PMID- 17035606
TI - Apparent mineralocorticoid excess: report of six new cases and extensive personal
experience.
AB - In mineralocorticoid target tissues such as the cortical collecting duct in the
kidney, the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) is
responsible for the peripheral inactivation of cortisol to cortisone, thereby
protecting the mineralocorticoid receptor from inappropriate activation by
cortisol. Mutations in the HSD11B2 gene cause the syndrome of apparent
mineralocorticoid excess, an autosomal recessive form of inherited hypertension
in which cortisol acts as a potent mineralocorticoid. Herein are described six
new families with mutations in the HSD11B2 gene causing hypokalemic hypertension,
with low plasma aldosterone and low renin levels in affected individuals,
indicating mineralocorticoid hypertension. Profiling of urinary steroid
metabolites showed decreased cortisol inactivation, with urinary
tetrahydrocortisol and tetrahydrocortisone ratio (THF + 5alphaTHF)/THE ranging
2.4 to 40 and nearly absent urinary free cortisone in all but one case. Genetic
analysis of the HSD11B2 gene from these patients with apparent mineralocorticoid
excess revealed distinct homozygous point mutations in four families, a compound
heterozygous mutation in one family, and a large 23-bp exonic insert with
frameshift and disruption of the amino acid sequence in another family.
Expression studies of mutants that were expressed in HEK-293 cells showed marked
reduction or abolition of 11betaHSD2 enzymatic activity. These cases are reviewed
along with previous ones from the authors' extensive personal experience to
highlight the importance of 11betaHSD2 in the understanding of a new biologic
principle in hormone action, demonstrating that local metabolism of the
glucocorticoid hormones into inactive derivatives by the enzyme 11betaHSD2 is one
of the mechanisms that intervene to allow specific aldosterone regulatory
effects.
PMID- 17035607
TI - No improvement of patient or graft survival in transplant recipients treated with
angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor
blockers: a collaborative transplant study report.
AB - It was reported recently that treatment of kidney transplant recipients with
angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor
blockers (ARB) is associated with strikingly improved long-term graft and patient
survival. This finding has important implications for future posttransplantation
therapy recommendations. In an analysis of 17,209 kidney and 1744 heart
transplant recipients, an association of treatment with ACEI/ARB with improved
transplant outcome could not be confirmed. It is concluded that recommendations
for a widespread use of ACEI/ARB treatment in transplant recipients are
unwarranted.
PMID- 17035608
TI - Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and
mechanisms of action.
PMID- 17035609
TI - Proteomic analysis of urine in kidney transplant patients with BK virus
nephropathy.
AB - The differentiation of BK virus-associated renal allograft nephropathy (BKVAN)
from acute allograft rejection (AR) in renal transplant recipients is an
important clinical problem because the treatment can be diametrically opposite
for the two conditions. The aim of this discovery-phase biomarker development
study was to examine feasibility of developing a noninvasive method to
differentiate BKVAN from AR. Surface-enhanced laser desorption/ionization (SELDI)
time-of-flight mass spectrometry analysis was used to compare proteomic profiles
of urine samples of 21 patients with BKVAN, 28 patients with AR (Banff Ia to
IIb), and 29 patients with stable graft function. SELDI analysis showed proteomic
profiles that were significantly different in the BKVAN group versus the AR and
stable transplant groups. Peaks that corresponded to m/z values of 5.872, 11.311,
11.929, 12.727, and 13.349 kD were significantly higher in patients with BKVAN.
Bioinformatics analyses allowed distinction of profiles of patients with BKVAN
from patients with AR and stable patients. SELDI profiles also showed a high
degree of reproducibility. Proteomic analysis of urine may offer a noninvasive
way to differentiate BKVAN from AR in clinical practice. The identification of
individual proteomic peaks can improve further the clinical utility of this
screening method.
PMID- 17035610
TI - Renal fibroblasts and myofibroblasts in chronic kidney disease.
PMID- 17035611
TI - How does proteinuria cause progressive renal damage?
AB - The possibility that proteinuria may accelerate kidney disease progression to end
stage renal failure has received support from the results of increasing numbers
of experimental and clinical studies. Evidence indicating that this process
occurs through multiple pathways, including induction of tubular chemokine
expression and complement activation that lead to inflammatory cell infiltration
in the interstitium and sustained fibrogenesis, is reviewed. Macrophages are
prominent in the interstitial inflammatory infiltrate. This cell type mediates
progression of renal injury to the extent that macrophage numbers in renal biopsy
predict renal survival in patients with chronic renal disease. Chemoattractants
and adhesive molecules for inflammatory cells are upregulated by excess
ultrafiltered protein load of proximal tubular cells via activation of NF-kappaB
dependent and NF-kappaB-independent pathways. This mechanism is a potential
target for therapeutic approaches, as shown by beneficial effects of
manipulations with inhibitory molecules of NF-kappaB activation or of chemokine
receptors in experimental studies. Targeting complement synthesis or activation
in proximal tubule might offer novel therapeutic opportunities. Finally, proximal
tubular cell receptors for uptake of plasma proteins that are under investigation
may provide activation signals on excess tubular protein handling.
PMID- 17035612
TI - Acute uremia but not renal inflammation attenuates aseptic acute lung injury: a
critical role for uremic neutrophils.
AB - Acute renal failure (ARF) remains a major clinical challenge, especially in the
intensive care setting. Mortality of ARF combined with acute lung injury (ALI) is
even higher and may reach 80%. Recent studies have suggested a remote effect of
ARF on pulmonary homeostasis. However, it is unknown whether and to what extent
ARF clinically affects pulmonary function, in particular oxygenation. For
elucidation of the impact of ARF on aseptic ALI, a murine two-hit model that
consists of acute uremia (AU) and subsequent ALI was developed. AU was induced by
renal ischemia-reperfusion (inflammatory AU) or bilateral nephrectomy
(noninflammatory AU). ALI was initiated by intratracheal HCl instillation and
characterized by severe, PMN-dependent decrease in arterial partial pressure of
O(2) (>70%) in nonuremic mice. Uremic mice, by contrast, showed a significant
protection from ALI (decrease in arterial partial pressure of O(2) <40%); this
was independent of the type of AU. Reconstitution experiments, in which uremic
neutrophils were injected into nonuremic mice and vice versa, identified uremic
neutrophils as the primary mediators. Between normal and uremic neutrophils,
there were no differences in apoptosis or superoxide production. Pulmonary
recruitment of uremic neutrophils, however, was significantly attenuated compared
with that of normal neutrophils. This defect was associated with altered surface
expression of L-selectin; sialyl Lewis(x), an L-selectin counterreceptor,
previously was proved to be critical in aseptic ALI. In conclusion, it is shown
that AU but not renal inflammation attenuates aseptic, neutrophil-dependent ALI
and exerts an anti-inflammatory effect by attenuating pulmonary neutrophil
recruitment.
PMID- 17035613
TI - Renin-angiotensin-aldosterone system and progression of renal disease.
AB - Inhibition of the renin-angiotensin-aldosterone system (RAAS) is one of the most
powerful maneuvers to slow progression of renal disease. Angiotensin II (AngII)
has emerged in the past decade as a multifunctional cytokine that exhibits many
nonhemodynamic properties, such as acting as a growth factor and profibrogenic
cytokine, and even having proinflammatory properties. Many of these deleterious
functions are mediated by other factors, such as TGF-beta and chemoattractants
that are induced in the kidney by AngII. Moreover, understanding of the RAAS has
become much more complex in recent years with the identification of novel
peptides (e.g., AngIV) that could bind to specific receptors, elucidating
deleterious effects, and non-angiotensin-converting enzyme (ACE)-mediated
generation of AngII. The ability of renal cells to produce AngII in a
concentration that is much higher than what is found in the systemic circulation
and the observation that aldosterone may be engaged directly in profibrogenic
processes independent of hypertension have added to the complexity of the RAAS.
Even renin has now been identified to have a "life on its own" and mediates
profibrotic effects via binding to specific receptors. Finally, drugs that are
used to block the RAAS, such as ACE inhibitors or certain AngII type 1 receptor
antagonists, may have properties on cells independent of AngII (ACE inhibitor
mediated outside-inside signaling and peroxisome proliferator-activated receptor
gamma stimulatory effects of certain sartanes). Although blockade of the RAAS
with ACE inhibitors, AngII type 1 receptor antagonists, or the combination of
both should be part of every strategy to slow progression of renal disease, a
better understanding of the novel aspects of the RAAS should contribute to the
development of innovative strategies not only to completely halt progression but
also to induce regression of human renal disease.
PMID- 17035614
TI - Partial neutralization of the acidogenic Western diet with potassium citrate
increases bone mass in postmenopausal women with osteopenia.
AB - Chronic acid loads are an obligate consequence of the high animal/grain protein
content of the Western diet. The effect of this diet-induced metabolic acidosis
on bone mass is controversial. In a randomized, prospective, controlled, double
blind trial, 161 postmenopausal women (age 58.6 +/- 4.8 yr) with low bone mass (T
score -1 to -4) were randomly assigned to 30 mEq of oral potassium (K) citrate
(Kcitrate) or 30 mEq of K chloride (KCl) daily. The primary end point was the
intergroup difference in mean percentage change in bone mineral density (BMD) at
lumbar spine (L2 through L4) after 12 mo. Compared with the women who received
KCl, women who received Kcitrate exhibited an intergroup increase in BMD (+/-SE)
of 1.87 +/- 0.50% at L2 through L4 (P < 0.001), of 1.39 +/- 0.48% (P < 0.001) at
femoral neck, and of 1.98 +/- 0.51% (P < 0.001) at total hip. Significant
secondary end point intragroup changes also were found: Kcitrate increased L2
through L4 BMD significantly from baseline at months 3, 9, and 12 and reached a
month 12 increase of 0.89 +/- 0.30% (P < 0.05), whereas the KCl arm showed a
decreased L2 through L4 BMD by -0.98 +/- 0.38% (P < 0.05), significant only at
month 12. Intergroup differences for distal radius and total body were NS. The
Kcitrate-treated group demonstrated a sustained and significant reduction in
urinary calcium excretion and a significant increase in urinary citrate
excretion, with increased citrate excretion indicative of sustained systemic
alkalization. Urinary bone resorption marker excretion rates were significantly
reduced by Kcitrate, and for deoxypyridinoline, the intergroup difference was
significant. Urinary net acid excretion correlated inversely and significantly
with the change in BMD in a subset of patients. Large and significant reductions
in BP were observed for both K supplements during the entire 12 mo. Bone mass can
be increased significantly in postmenopausal women with osteopenia by increasing
their daily alkali intake as citrate, and the effect is independent of reported
skeletal effects of K.
PMID- 17035615
TI - The chronic kidney disease epidemic: stepping back and looking forward.
AB - Estimating the prevalence of chronic kidney disease (CKD) is no simple task. The
overall prevalence is relatively low but may be higher in select populations that
are not accessible to surveys (e.g., certain ethnic groups, the sick or elderly).
Moreover, the tests that define CKD lack precision and transportability to
healthy populations. During the past decade, it is not clear that CKD has grown
substantially. Some epidemiologic factors that are associated with CKD (obesity
and diabetes) are increasing, whereas others (uncontrolled hypertension and
smoking) are decreasing. Reasons for the discrepancy between a stable CKD
population and ongoing ESRD growth remain speculative. There is evidence that
ESRD rates may be stabilizing and that efforts to reduce progression in high-risk
groups may be starting to show benefit. Expanding the definition of CKD and
increasing detection may be required to reduce overall ESRD prevalence. One
concern is that many of the well-defined high-risk patient groups (diabetes and
black) are still undertreated. Increasing the investigation and treatment of low
risk patients may not be the answer. Clinical inertia (failure to initiate or
change therapy) may be a more significant and modifiable barrier toward reducing
ESRD, and this deserves increased attention. Furthermore, reducing CKD prevalence
will require controlling the precipitating causes. The incremental benefit of
detecting CKD in low-risk patients, use of expensive therapies in CKD, or new
strategies such as the treatment of prehypertension require solid evidence, not
only of the variety that shows benefit (hard end points) but also to whom, when,
and at what cost.
PMID- 17035616
TI - Posttransplantation anemia at 12 months in kidney recipients treated with
mycophenolate mofetil: risk factors and implications for mortality.
AB - Although posttransplantation anemia (PTA) is common in the mycophenolate mofetil
era, its impact on patient survival is unknown. This retrospective cohort study
characterized factors that are associated with PTA 12 mo after transplantation in
mycophenolate mofetil-treated kidney recipients and explored whether 12-mo PTA
affects outcomes. The records of 626 kidney recipients were examined for presence
of anemia (hemoglobin <12 g/dl). Multivariate regression models, fit with
covariates that had unadjusted relationships, investigated both risk factors for
12-mo PTA and whether 12-mo PTA contributes to mortality. Anemia prevalence was
72, 40, and 20.3% at 1, 3, and 12 mo, respectively. By multivariate logistic
regression, anemia at 3 mo (odds ratio [OR] 10.0; 95% confidence interval [CI]
5.3 to 17.1; P = 0.0001), donor age (OR 1.0; 95% CI 1.1 to 1.3; P = 0.005), and 3
mo creatinine (OR 2.0; 95% CI 1.2 to 3.3; P = 0.044) were associated with 12-mo
PTA. The PTA cohort had inferior patient survival (P = 0.02, log rank) and a
higher proportion of cardiovascular deaths (6.3 versus 2.2%; P = 0.017) than
nonanemic patients. By Cox regression, 12-mo PTA (hazard ratio [HR] 3.0; 95% CI
1.3 to 6.7; P = 0.009), 12-mo creatinine (HR 1.3; 95% CI 1.1 to 1.4; P = 0.008),
age at transplantation (HR 1.1; 95% CI 1.1 to 1.2; P = 0.004), and hepatitis C
seropositivity (HR 2.8; 95% CI 1.1 to 7.0; P = 0.03) were associated with
mortality. There was no interaction between 12-mo PTA and serum creatinine. In
conclusion, 12-mo PTA is associated with an increased risk for patient death. The
presence of anemia 3 mo after kidney transplantation is a major determinant of 12
mo PTA. PTA in kidney recipients therefore should be defined by its persistence
or occurrence beyond the third posttransplantation month.
PMID- 17035617
TI - Influence of recombinant human relaxin on renal hemodynamics in healthy
volunteers.
AB - Maternal renal hemodynamic adaptation to human pregnancy is one of the most
dramatic of all physiologic changes, but the factors that are responsible have
remained elusive. In rat pregnancy, there are comparable renal hemodynamic
changes, and in this species there is comprehensive evidence that the ovarian
hormone relaxin (RLX) is responsible. This study investigated the renal effects
of recombinant human RLX (rhRLX) in humans. Eleven volunteers (six male, five
female) received intravenous infusions of rhRLX over 5 h at an infusion rate that
was chosen to sustain serum concentrations that are comparable to early
pregnancy. The renal clearances of inulin and para-aminohippurate were used to
measure GFR and renal plasma flow, respectively. Irrespective of gender, renal
plasma flow was increased by 47% compared with baseline levels (P < 0.0001), but
no significant change was observed in GFR. There were no side effects or adverse
reactions of rhRLX given as an intravenous infusion, and the data suggest that
RLX indeed may be one of the elusive renal vasodilatory factors in human
pregnancy. Further work is necessary to elucidate the complimentary factors that
permit the concomitant increase in GFR during pregnancy.
PMID- 17035619
TI - Serial Aspergillus antigen monitoring in pediatric bone marrow transplant
patients.
AB - Invasive aspergillosis carries a high mortality rate in immunocompromised
patients, such as bone marrow transplant patients. Favorable outcomes are
dependent on early detection and treatment. Positive galactomannan antigenemia
has been included as a microbiological criterion for probable or possible
diagnosis of invasive aspergillosis. Detection of circulating Aspergillus DNA in
the first positive galactomannan sample, with serial monitoring, could help in
diagnosis of invasive aspergillosis in bone marrow transplant patients. Morbidity
and mortality from aspergillosis can possibly be reduced if an early diagnosis is
made and appropriate treatment initiated. An effective and accurate way of early
detection of invasive aspergillosis is serial Aspergillus antigen monitoring.
PMID- 17035620
TI - An examination of fatigue in advanced childhood cancer.
AB - Fatigue is a complex phenomenon without a widely accepted definition, and is one
of the least explained phenomena of advanced disease. A great deal of work and
research has been done to explore the experience, incidence, and management of
fatigue in children with cancer. Fatigue remains, however, a source of suffering
for children with advanced disease and their families. The knowledge we have
gained from the study of fatigue in children receiving antineoplastic therapy can
be applied to children during this phase of their illness. The goal of this
article is to address the incidence of fatigue in the advanced stage of illness,
review the literature regarding fatigue in pediatric oncology, and propose how
such findings may be applicable to children in the later stages of their illness.
PMID- 17035621
TI - Assessing procedural pain in children with cancer in Beirut, Lebanon.
AB - This study describes the relationship between different indicators of pain,
including self-reports, behavioral observations, and physiological measures, in
children with cancer undergoing invasive procedures. Forty-five children between
the ages of 4 and 10 years were evaluated while undergoing Port-a-Cath access.
The study was conducted in the outpatient clinics of the Children's Cancer Center
in Beirut, Lebanon. Children used 2 self-report measures of pain (the Wong-Baker
FACES Pain Rating Scale and an adaptation of the FACES, the DOLLS). Parents and
nurses assessed the child's pain on the FACES and the child's distress on the
Observational Scale of Behavioral Distress-Revised. Nurses recoded behavioral
observations as well as physiological responses to pain. There was a high degree
of consistency between the self-reports and moderate to high correlations between
self-reports, behavioral parameters, and physiological parameters, suggesting
that accurate pain assessments can be made by both nurses and parents. The
results also demonstrate adequate validity and reliability of the DOLLS scale in
a Lebanese population, in addition to being the preferred assessment tool for all
the children in the study.
PMID- 17035622
TI - The role of cognitive remediation in childhood cancer survivors experiencing
neurocognitive late effects.
AB - With the increasing number of children becoming long-term cancer survivors, it
has become evident that these survivors are experiencing long-term neurocognitive
deficits. Many of these deficits have been found to be the result of cancer
related therapies including intravenous and intrathecal chemotherapy and cranial
radiation. These neurocognitive deficits include learning disabilities, cognitive
deficits, attention disorders, and difficulties with memory. Cognitive
remediation therapy uses a systematic approach to learning strategies that is
aimed to equip these affected children with proper, effective, and proven
learning strategies. This article will briefly discuss the neurocognitive
deficits experienced by long-term childhood cancer survivors. Cognitive
remediation therapy will then be introduced with specific attention to the
cognitive remediation program developed by Butler and Copeland. Finally,
implications for practice and future research will be discussed.
PMID- 17035623
TI - The effect of clinic-based health promotion education on perceived health status
and health promotion behaviors of adolescent and young adult cancer survivors.
AB - More than 70% of children/adolescents diagnosed with cancer are long-term
survivors. Little is known about the health perceptions and practices of this
population, and limited previous studies have come exclusively from a risk
reduction/health protection model rather than a health promotion model. This
study was conducted to describe the perceived health status and health-promoting
behaviors of adolescent/young adult cancer survivors. This study used Pender's
revised health promotion model; perceived health status and health-promoting
behaviors were measured using the General Health Index (GHRI) and the Health
Promoting Lifestyle Profile II (HPLP-II). The sample consisted of 60 cancer
survivors 2 years after completion of cancer treatment and attending a
survivorship clinic. Mean baseline scores for the GHRI (76.66; SD, 10.41)
indicate perceived health status is positive and similar to normative (noncancer
survivor) adolescent/young adult samples. Surprisingly, there was no correlation
between scores on the GHRI and the HPLP-II in this sample (r = 0.03).
PMID- 17035624
TI - Transitioning to survivorship: a pilot study.
AB - There are no clear transition guidelines for adolescent and young adult cancer
patients, their parents, and their primary care providers (PCPs) when completing
active therapy and within the first few years after therapy. The purpose of this
pilot study was to identify needs and concerns of recently treated adolescent
cancer patients and their parents, young adult cancer survivors, and the
community PCPs of adolescent patients. Four focus group interviews were conducted
with survivors and parents, and 3 in-depth interviews were conducted with PCPs.
All interviews were audiotaped and transcribed for content analysis. A range of
needs were identified, including lack of adequate written and verbal information
about their prior treatment, its potential side effects, and appropriate follow
up care. The best sources for education were identified as the primary
oncologist, nurse practitioner, or nurse. At completion of treatment, parents and
adult survivors felt a lack of psychosocial support. Suggestions from
participants included use of informational videos for survivors, weekend
education and support programs, ongoing support groups, use of the Internet, and
educational newsletters. The PCPs reported a lack of general pediatric oncology
knowledge and specific patient information, time constraints in their patient
schedules, and having few survivors in their practices as barriers to optimal
survivorship care. Further research is needed to look at the unmet educational
and psychological needs of childhood cancer survivors and their parents during
the critical time when they transition off treatment.
PMID- 17035625
TI - Development of a screening assay for surrogate markers of CHK1 inhibitor-induced
cell cycle release.
AB - Chk1 is a key regulator of the S and G2/M checkpoints and is activated following
DNA damage by agents such as the topoisomerase I inhibitor camptothecin (CPT). It
has been proposed that Chk1 inhibitors used in combination with such a DNA
damaging agent to treat tumors would potentiate cytotoxicity and increase the
therapeutic index, particularly in tumors lacking functional p53. The aim of this
study was to determine whether gene expression analysis could be used to inform
lead optimization of a novel series of Chk1 inhibitors. The candidate small
molecule Chk1 inhibitors were used in combination with CPT to identify potential
markers of functional Chk1 inhibition, as well as resulting cell cycle
progression, using cDNA-based microarrays. Differential expression of several of
these putative marker genes was further validated by RT-PCR for use as a medium
throughput assay. In the presence of DNA damage, Chk1 inhibitors altered CPT
dependent effects on the expression of cell cycle and DNA repair genes in a
manner consistent with a Chk1-specific mechanism of action. Furthermore,
differential expression of selected marker genes, cyclin E2, EGR1, and DDIT3, was
dose dependent for Chk1 inhibition. RT-PCR results for these genes following
treatment with a panel of Chk1 inhibitors showed a strong correlation between
marker gene response and the ability of each compound to abrogate cell cycle
arrest in situ following CPT-induced DNA damage. These results demonstrate the
utility of global expression analysis to identify surrogate markers, providing an
alternative method for rapid compound characterization to support advancement
decisions in early drug discovery.
PMID- 17035628
TI - GPI-anchored proteins and free GPI glycolipids of procyclic form Trypanosoma
brucei are nonessential for growth, are required for colonization of the tsetse
fly, and are not the only components of the surface coat.
AB - The procyclic form of Trypanosoma brucei exists in the midgut of the tsetse fly.
The current model of its surface glycocalyx is an array of rod-like procyclin
glycoproteins with glycosylphosphatidylinositol (GPI) anchors carrying sialylated
poly-N-acetyllactosamine side chains interspersed with smaller sialylated poly-N
acetyllactosamine-containing free GPI glycolipids. Mutants for TbGPI12, deficient
in the second step of GPI biosynthesis, were devoid of cell surface procyclins
and poly-N-acetyllactosamine-containing free GPI glycolipids. This major
disruption to their surface architecture severely impaired their ability to
colonize tsetse fly midguts but, surprisingly, had no effect on their morphology
and growth characteristics in vitro. Transmission electron microscopy showed that
the mutants retained a cell surface glycocalyx. This structure, and the viability
of the mutants in vitro, prompted us to look for non-GPI-anchored parasite
molecules and/or the adsorption of serum components. Neither were apparent from
cell surface biotinylation experiments but [3H]glucosamine biosynthetic labeling
revealed a group of previously unidentified high apparent molecular weight
glycoconjugates that might contribute to the surface coat. While characterizing
GlcNAc-PI that accumulates in the TbGPI12 mutant, we observed
inositolphosphoceramides for the first time in this organism.
PMID- 17035629
TI - Bypassing the catalytic activity of SIR2 for SIR protein spreading in
Saccharomyces cerevisiae.
AB - Sir protein spreading along chromosomes and silencing in Saccharomyces cerevisiae
requires the NAD+-dependent histone deacetylase activity of Sir2p. We tested
whether this requirement could be bypassed at the HM loci and telomeres in cells
containing a stably expressed, but catalytically inactive mutant of Sir2p, sir2
345p, plus histone mutants that mimic the hypoacetylated state normally created
by Sir2p. Sir protein spreading was rescued in sir2-345 mutants expressing
histones in which key lysine residues in their N-termini had been mutated to
arginine. Mating in these mutants was also partially restored upon overexpression
of Sir3p. Together, these results indicate that histone hypoacetylation is
sufficient for Sir protein spreading in the absence of production of 2'-O-acetyl
ADP ribose by sir2p and Sir2p's enzymatic function for silencing can be bypassed
in a subset of cells in a given population. These results also provide genetic
evidence for the existence of additional critical substrates of Sir2p for
silencing in vivo.
PMID- 17035630
TI - Functional analysis of AP-2 alpha and mu2 subunits.
AB - The AP-2 adaptor complex plays a key role in cargo recognition and clathrin
coated vesicle formation at the plasma membrane. To investigate the functions of
individual binding sites and domains of the AP-2 complex in vivo, we have stably
transfected HeLa cells with wild-type and mutant small interfering RNA-resistant
alpha and mu2 subunits and then used siRNA knockdowns to deplete the endogenous
proteins. Mutating the PtdIns(4,5)P2 binding site of alpha, the phosphorylation
site of mu2, or the YXXPhi binding site of mu2 impairs AP-2 function, as assayed
by transferrin uptake. In contrast, removing the C-terminal appendage domain of
alpha, or mutating the PtdIns(4,5)P2 binding site of mu2, has no apparent effect.
However, adding a C-terminal GFP tag to alpha renders it completely
nonfunctional. These findings demonstrate that there is some functional
redundancy in the binding sites of the various AP-2 subunits, because no single
mutation totally abolishes function. They also help to explain why GFP-tagged AP
2 never appears to leave the plasma membrane in some live cell imaging studies.
Finally, they establish a new model system that can be used both for additional
structure-function analyses, and as a way of testing tagged constructs for
function in vivo.
PMID- 17035631
TI - Ubc9 regulates mitosis and cell survival during zebrafish development.
AB - Many proteins are modified by conjugation with Sumo, a gene-encoded, ubiquitin
related peptide, which is transferred to its target proteins via an enzymatic
cascade. A central component of this cascade is the E2-conjugating enzyme Ubc9,
which is highly conserved across species. Loss-of-function studies in yeast,
nematode, fruit fly, and mouse blastocystes point to multiple roles of Ubc9
during cell cycle regulation, maintenance of nuclear architecture, chromosome
segregation, and viability. Here we show that in zebrafish embryos, reduction of
Ubc9 activity by expression of a dominant negative version causes widespread
apoptosis, similar to the effect described in Ubc9-deficient mice. However,
antisense-based knock down of zygotic ubc9 leads to much more specific defects in
late proliferating tissues, such as cranial cartilage and eyes. Affected
cartilaginous elements are of relatively normal size and shape, but consist of
fewer and larger cells. Stainings with mitotic markers and 5-Bromo-2'
deoxyuridine incorporation studies indicate that fewer chondrocyte precursors are
in mitosis, whereas the proportion of cells in S-phase is unaltered.
Consistently, FACS analyses reveal an increase in the number of cells with a DNA
content of 4n or even 8n. Our data indicate an in vivo requirement of Ubc9 for
G2/M transition and/or progression through mitosis during vertebrate
organogenesis. Failed mitosis in the absence of Ubc9 is not necessarily coupled
with cell death. Rather, cells can continue to replicate their DNA, grow to a
larger size, and finish their normal developmental program.
PMID- 17035632
TI - Reconstruction of the kinetochore during meiosis in fission yeast
Schizosaccharomyces pombe.
AB - During the transition from mitosis to meiosis, the kinetochore undergoes
significant reorganization, switching from a bipolar to a monopolar orientation.
To examine the centromere proteins that are involved in fundamental
reorganization in meiosis, we observed the localization of 22 mitotic and 2
meiotic protein components of the kinetochore during meiosis in living cells of
the fission yeast. We found that the 22 mitotic proteins can be classified into
three groups: the Mis6-like group, the NMS (Ndc80-Mis12-Spc7) group, and the DASH
group, based on their meiotic behavior. Mis6-like group proteins remain at the
centromere throughout meiosis. NMS group proteins disappear from the centromere
at the onset of meiosis and reappear at the centromere in two steps in late
prophase. DASH group proteins appear shortly before metaphase of meiosis I. These
observations suggest that Mis6-like group proteins constitute the structural
basis of the centromere and that the NMS and DASH group proteins reassemble to
establish the functional metaphase kinetochore. On the other hand, the meiosis
specific protein Moa1, which plays an important role in forming the meiotic
monopolar kinetochore, is loaded onto the centromere significantly earlier than
the NMS group, whereas another meiosis-specific protein, Sgo1, is loaded at times
similar to the NMS group.
PMID- 17035633
TI - Wnt5a signaling induces proliferation and survival of endothelial cells in vitro
and expression of MMP-1 and Tie-2.
AB - Wnts are lipid-modified secreted glycoproteins that regulate diverse biological
processes. We report that Wnt5a, which functions in noncanonical Wnt signaling,
has activity on endothelial cells. Wnt5a is endogenously expressed in human
primary endothelial cells and is expressed in murine vasculature at several sites
in mouse embryos and tissues. Expression of exogenous Wnt5a in human endothelial
cells promoted angiogenesis. Wnt5a induced noncanonical Wnt signaling in
endothelial cells, as measured by Dishevelled and ERK1/2 phosphorylation, and
inhibition of canonical Wnt signaling, a known property of Wnt5a. Wnt5a induced
endothelial cell proliferation and enhanced cell survival under serum-deprived
conditions. The Wnt5a-mediated proliferation was blocked by Frizzled-4
extracellular domain. Wnt5a expression enhanced capillary-like network formation,
whereas reduction of Wnt5a expression decreased network formation. Reduced Wnt5a
expression inhibited endothelial cell migration. Screening for Wnt5a-regulated
genes in cultured endothelial cells identified several encoding angiogenic
regulators, including matrix metalloproteinase-1, an interstitial collagenase,
and Tie-2, a receptor for angiopoietins. Thus, Wnt5a acts through noncanonical
Wnt signaling to promote angiogenesis.
PMID- 17035634
TI - The unfolded protein response transducer Ire1p contains a nuclear localization
sequence recognized by multiple beta importins.
AB - The Ire1p transmembrane receptor kinase/endonuclease transduces the unfolded
protein response (UPR) from the endoplasmic reticulum (ER) to the nucleus in
Saccharomyces cerevisiae. In this study, we analyzed the capacity of a highly
basic sequence in the linker region of Ire1p to function as a nuclear
localization sequence (NLS) both in vivo and in vitro. This 18-residue sequence
is capable of targeting green fluorescent protein to the nucleus of yeast cells
in a process requiring proteins involved in the Ran GTPase cycle that facilitates
nuclear import. Mutagenic analysis and importin binding studies demonstrate that
the Ire1p linker region contains overlapping potential NLSs: at least one
classical NLS (within sequences 642KKKRKR647 and/or 653KKGR656) that is
recognized by yeast importin alpha (Kap60p) and a novel betaNLS
(646KRGSRGGKKGRK657) that is recognized by several yeast importin beta
homologues. Kinetic binding data suggest that binding to importin beta proteins
would predominate in vivo. The UPR, and in particular ER stress-induced HAC1 mRNA
splicing, is inhibited by point mutations in the Ire1p NLS that inhibit nuclear
localization and also requires functional RanGAP and Ran GEF proteins. The NLS
dependent nuclear localization of Ire1p would thus seem to be central to its role
in UPR signaling.
PMID- 17035635
TI - Extracellular signal-regulated kinase 1/2 activity is not required in mammalian
cells during late G2 for timely entry into or exit from mitosis.
AB - Extracellular signal-regulated kinase (ERK)1/2 activity is reported to be
required in mammalian cells for timely entry into and exit from mitosis (i.e.,
the G2-mitosis [G2/M] and metaphase-anaphase [M/A] transitions). However, it is
unclear whether this involvement reflects a direct requirement for ERK1/2
activity during these transitions or for activating gene transcription programs
at earlier stages of the cell cycle. To examine these possibilities, we followed
live cells in which ERK1/2 activity was inhibited through late G2 and mitosis. We
find that acute inhibition of ERK1/2 during late G2 and through mitosis does not
affect the timing of the G2/M or M/A transitions in normal or transformed human
cells, nor does it impede spindle assembly, inactivate the p38 stress-activated
checkpoint during late G2 or the spindle assembly checkpoint during mitosis.
Using CENP-F as a marker for progress through G2, we also show that sustained
inhibition of ERK1/2 transiently delays the cell cycle in early/mid-G2 via a p53
dependent mechanism. Together, our data reveal that ERK1/2 activity is required
in early G2 for a timely entry into mitosis but that it does not directly
regulate cell cycle progression from late G2 through mitosis in normal or
transformed mammalian cells.
PMID- 17035637
TI - Effect of transgene concentration, flanking matrix attachment regions, and RecA
coating on the efficiency of mouse transgenesis mediated by intracytoplasmic
sperm injection.
AB - Intracytoplasmic sperm injection (ICSI) of DNA-loaded sperm cells has been shown
to be a valuable tool for the production of transgenic animals, especially when
DNA constructs with submegabase magnitude are used. In order to optimize and to
understand the mechanism of the ICSI-mediated transgenesis, we have evaluated the
impact of transgene DNA concentration, transgene flanking with nuclear matrix
attachment regions (MARs), and the use of recombinase A (RecA)-coated DNA on the
efficiency of mouse transgenesis production by ICSI. Presented data include
assays with three DNA constructs; an enhanced green fluorescent protein (EGFP)
plasmid of 5.4 kb, this plasmid flanked with two MAR elements (2.3 Kb of the
human beta-interferon domain boundaries), and a yeast artificial chromosome (YAC)
construct of approximately 510 kb (the largest transgenic construct introduced by
ICSI that we have seen reported). ICSI-mediated transgenesis was done in the B6D2
mouse strain using different concentrations for each construct. Analysis of
generated data indicated that ICSI allows the use of higher DNA concentrations
than the ones used for pronuclear microinjection, however, when a certain
threshold is exceeded, embryo/fetal viability decrease dramatically. In addition,
independently of the transgene concentration tested, transgene flanking with MAR
sequences did not have a significant impact on the efficiency of this
transgenesis method. Finally, we observed that although the overall efficiency of
ICSI-mediated transgenesis with fresh spermatozoa and RecA-complexed DNA was
similar to the one obtained with the common ICSI-mediated transgenesis approach
with frozen-thawed spermatozoa and RecA free DNA, this method was not as
efficient in maintaining a low frequency of founder animal mosaicism, suggesting
that different mechanisms of transgene integration might result from each
procedure.
PMID- 17035636
TI - A nuclear function of Hu proteins as neuron-specific alternative RNA processing
regulators.
AB - Recent advances in genome-wide analysis of alternative splicing indicate that
extensive alternative RNA processing is associated with many proteins that play
important roles in the nervous system. Although differential splicing and
polyadenylation make significant contributions to the complexity of the nervous
system, our understanding of the regulatory mechanisms underlying the neuron
specific pathways is very limited. Mammalian neuron-specific embryonic lethal
abnormal visual-like Hu proteins (HuB, HuC, and HuD) are a family of RNA-binding
proteins implicated in neuronal differentiation and maintenance. It has been
established that Hu proteins increase expression of proteins associated with
neuronal function by up-regulating mRNA stability and/or translation in the
cytoplasm. We report here a novel function of these proteins as RNA processing
regulators in the nucleus. We further elucidate the underlying mechanism of this
regulation. We show that in neuron-like cells, Hu proteins block the activity of
TIA-1/TIAR, two previously identified, ubiquitously expressed proteins that
promote the nonneuronal pathway of calcitonin/calcitonin gene-related peptide
(CGRP) pre-mRNA processing. These studies define not only the first neuron
specific regulator of the calcitonin/CGRP system but also the first nuclear
function of Hu proteins.
PMID- 17035638
TI - Identification, culture, and characterization of germline stem cell-like cells in
chicken testes.
AB - We recently succeeded in inducing germline transmission by transferring chicken
testicular cells into heterologous testes. This study was designed subsequently
to identify pluripotent cells in the testicular cells, which would induce the
germline transmission. Testicular cells retrieved from juvenile (4-wk-old) or
adult (24-wk-old) White Leghorn (WL) chickens were stained with germ cell
specific markers anti-SSEA1, anti-SSEA3, anti-SSEA4, anti-EMA1, anti-ITGA6, and
anti-ITGB1 antibodies; 2C9; and lectin-Solanum tuberosum agglutinin (STA). The
percentages of the cells that were positive for each marker were within the
ranges of 0.33% -0.44% and 0.029%-0.072% of the total testicular cell population
in the juvenile and adult, respectively, and significant (P < 0.0002) differences
were detected between the ages. When 1 x 10(6) testicular cells were cultured in
Dulbecco minimum essential medium-based medium supplemented with leukemia
inhibitory factor (LIF), basic fibroblast growth factor (FGF2), and/or
insulinlike growth factor 1 (IGF1), colony formation was detected only in
LIF++FGF2-containing or LIF+FGF2+IGF1-containing medium during primary culture,
and the supplementation of LIF+FGF2+IGF1 was the most efficient for maintaining
the colony-forming cells through subculture. The established cells retrieved at
the end of the primary culture or the 20th subpassage were positive for chicken
germ cell-specific periodic acid-Schiff (PAS), EMA1, 2C9, SSEA1, SSEA3, SSEA4,
ITGA6, and ITGB1; and lectin-STA markers (evaluated after 11th subpassage).
Double staining of lectin-STA with anti-SSEA1, anti-SSEA3, anti-SSEA4, anti
ITGA6, and anti-ITGB1 also was possible. They differentiated spontaneously into
embryoid bodies after being cultured in LIF-free medium. We conclude that
germline stem cell-like cells are present in chicken testicular cells retrieved
from both juvenile and adult testes, which can be identified with the specific
markers for primordial germ cells or embryonic germ cells.
PMID- 17035639
TI - The cytotrophoblast layer of human chorionic villi becomes thinner but maintains
its structural integrity during gestation.
AB - Chorionic villi in the human placenta serve as essential structures in
fetomaternal exchanges. According to the embryology and placentology literature,
during the first trimester, the cytotrophoblast (CTB) layer that is subjacent to
the syncytiotrophoblast (STB) and supported by a basal lamina is nearly complete,
but later, it becomes discontinuous. In the present study, we investigated the
structural integrity of the CTB layer in the normal villous tree by advanced
microscopy techniques using an antibody to hepatocyte growth factor (HGF)
activator inhibitor type 1 (SPINT1), a potent inhibitor of HGF activators
expressed exclusively on villous CTB. In full-term placenta, the cell surface of
the CTB layer was spread over the basal lamina but was not interrupted.
Morphometric analysis showed that throughout the villous tree, 80% of the
continuity of the CTB layer of full-term placenta and 90% of that of first
trimester placenta were preserved. Gestation was accompanied by unique structural
change in the basal domain of the trophoblast layer. The initially cuboidal
shaped CTB cells were transformed to flat cells with many cellular processes
that, together with those of the adjacent STB, eventually covered the trophoblast
basal lamina in a complex network of interdigitations. In addition, the
expression levels of SPINT1, ST14, HGF, and MET mRNAs in the villous tree
increased over the course of gestation. These results suggest that the structural
integrity of the SPINT1-positive CTB layer may play an important role in villous
differentiation and in maintenance of the villous tree via the HGF signaling
system during gestation.
PMID- 17035640
TI - In the absence of the mouse DNA/RNA-binding protein MSY2, messenger RNA
instability leads to spermatogenic arrest.
AB - MSY2 is a member of the Y-box family of proteins solely expressed in male and
female germ cells. In the male, MSY2 serves as a coactivator of transcription by
binding to a consensus promoter element present in many germ cell-specific genes.
In the nucleus, MSY2 marks specific mRNAs for cytoplasmic storage, stabilization,
and suppression of translation. The inactivation of MSY2 by gene targeting leads
to spermatogenic arrest and infertility. In testes of mice lacking MSY2,
incomplete nuclear condensation is prominent in later-stage spermatids at the
time of massive spermatid loss. Because MSY2 interacts with DNA and mRNAs, there
are several distinct sites of action, which could be disrupted in mice that lack
MSY2, resulting in the arrest of spermatogenesis. To define the molecular
cause(s) of the spermatogenic arrest in mice lacking MSY2, transcriptional and
posttranscriptional processes were assayed. Transcription, mRNA processing, and
mRNA intracellular transport appear normal in the absence of MSY2. However, a
redistribution of mRNAs from ribonucleoprotein particles to polysomes and marked
decreases were detected for many meiotic and postmeiotic germ cell mRNAs,
including the mRNAs encoding the transition proteins and protamines. This
suggests that increased mRNA instability is a likely cause of the male
infertility in Msy2-null mice.
PMID- 17035641
TI - Regulated mitochondrial DNA replication during oocyte maturation is essential for
successful porcine embryonic development.
AB - Cellular ATP is mainly generated through mitochondrial oxidative phosphorylation,
which is dependent on mitochondrial DNA (mtDNA). We have previously demonstrated
the importance of oocyte mtDNA for porcine and human fertilization. However, the
role of nuclear-encoded mitochondrial replication factors during oocyte and
embryo development is not yet understood. We have analyzed two key factors,
mitochondrial transcription factor A (TFAM) and polymerase gamma (POLG), to
determine their role in oocyte and early embryo development. Competent and
incompetent oocytes, as determined by brilliant cresyl blue (BCB) dye, were
assessed intermittently during the maturation process for TFAM and POLG mRNA
using real-time RT-PCR, for TFAM and POLG protein using immunocytochemistry, and
for mtDNA copy number using real-time PCR. Analysis was also carried out
following treatment of maturing oocytes with the mtDNA replication inhibitor,
2',3'-dideoxycytidine (ddC). Following in vitro fertilization, preimplantation
embryos were also analyzed. Despite increased levels of TFAM and POLG mRNA and
protein at the four-cell stage, no increase in mtDNA copy number was observed in
early preimplantation development. To compensate for this, mtDNA appeared to be
replicated during oocyte maturation. However, significant differences in nuclear
encoded regulatory protein expression were observed between BCB(+) and BCB(-)
oocytes and between untreated oocytes and those treated with ddC. These changes
resulted in delayed mtDNA replication, which correlated to reduced fertilization
and embryonic development. We therefore conclude that adherence to the regulation
of the timing of mtDNA replication during oocyte maturation is essential for
successful embryonic development.
PMID- 17035642
TI - CDH1 is a specific marker for undifferentiated spermatogonia in mouse testes.
AB - In the mammalian testis, spermatogenesis is initiated from a subset of stem cells
belonging to undifferentiated type A spermatogonia. In spite of the biologic
significance of undifferentiated type A spermatogonia, little is known about
their behavior and properties because of a lack of specific cell surface markers.
Here we show that CDH1 (previously known as E-cadherin) is expressed specifically
in undifferentiated type A spermatogonia in the mouse testis. Histologic analysis
showed that CDH1-positive cells had all the characteristics of undifferentiated
type A spermatogonia. Whole-mount immunohistochemistry showed that CDH1-positive
cells made clusters mainly comprising one, two, four, or eight cells. They
survived after administration of the cytotoxic agent busulfan to mice, and then
regenerated seminiferous epithelia. Transplantation experiments showed that only
CDH1-positive cells had colonizing activity in the recipient testis. Our data
clearly demonstrated that spermatogenic stem cells reside among undifferentiated
type A spermatogonia, which express CDH1.
PMID- 17035643
TI - Videos in clinical medicine. Thoracentesis.
PMID- 17035644
TI - Body of research--ownership and use of human tissue.
PMID- 17035645
TI - Doctors on strike--the crisis in German health care delivery.
PMID- 17035646
TI - The two-edged sword of curing childhood cancer.
PMID- 17035647
TI - Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's
disease.
AB - BACKGROUND: Second-generation (atypical) antipsychotic drugs are widely used to
treat psychosis, aggression, and agitation in patients with Alzheimer's disease,
but their benefits are uncertain and concerns about safety have emerged. We
assessed the effectiveness of atypical antipsychotic drugs in outpatients with
Alzheimer's disease. METHODS: In this 42-site, double-blind, placebo-controlled
trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or
agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per
day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per
day), or placebo. Doses were adjusted as needed, and patients were followed for
up to 36 weeks. The main outcomes were the time from initial treatment to the
discontinuation of treatment for any reason and the number of patients with at
least minimal improvement on the Clinical Global Impression of Change (CGIC)
scale at 12 weeks. RESULTS: There were no significant differences among
treatments with regard to the time to the discontinuation of treatment for any
reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks),
risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The
median time to the discontinuation of treatment due to a lack of efficacy favored
olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine
(9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of
treatment due to adverse events or intolerability favored placebo. Overall, 24%
of patients who received olanzapine, 16% of patients who received quetiapine, 18%
of patients who received risperidone, and 5% of patients who received placebo
discontinued their assigned treatment owing to intolerability (P=0.009). No
significant differences were noted among the groups with regard to improvement on
the CGIC scale. Improvement was observed in 32% of patients assigned to
olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to
risperidone, and 21% of patients assigned to placebo (P=0.22). CONCLUSIONS:
Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs
for the treatment of psychosis, aggression, or agitation in patients with
Alzheimer's disease. (ClinicalTrials.gov number, NCT00015548
[ClinicalTrials.gov].).
PMID- 17035648
TI - Microscopic-observation drug-susceptibility assay for the diagnosis of TB.
AB - BACKGROUND: New diagnostic tools are urgently needed to interrupt the
transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid,
sensitive detection of tuberculosis and multidrug-resistant tuberculosis in
sputum has been demonstrated in proof-of-principle studies of the microscopic
observation drug-susceptibility (MODS) assay, in which broth cultures are
examined microscopically to detect characteristic growth. METHODS: In an
operational setting in Peru, we investigated the performance of the MODS assay
for culture and drug-susceptibility testing in three target groups: unselected
patients with suspected tuberculosis, prescreened patients at high risk for
tuberculosis or multidrug-resistant tuberculosis, and unselected hospitalized
patients infected with the human immunodeficiency virus. We compared the MODS
assay head-to-head with two reference methods: automated mycobacterial culture
and culture on Lowenstein-Jensen medium with the proportion method. RESULTS: Of
3760 sputum samples, 401 (10.7%) yielded cultures positive for Mycobacterium
tuberculosis. Sensitivity of detection was 97.8% for MODS culture, 89.0% for
automated mycobacterial culture, and 84.0% for Lowenstein-Jensen culture
(P<0.001); the median time to culture positivity was 7 days, 13 days, and 26
days, respectively (P<0.001), and the median time to the results of
susceptibility tests was 7 days, 22 days, and 68 days, respectively. The
incremental benefit of a second MODS culture was minimal, particularly in
patients at high risk for tuberculosis or multidrug-resistant tuberculosis.
Agreement between MODS and the reference standard for susceptibility was 100% for
rifampin, 97% for isoniazid, 99% for rifampin and isoniazid (combined results for
multidrug resistance), 95% for ethambutol, and 92% for streptomycin (kappa
values, 1.0, 0.89, 0.93, 0.71, and 0.72, respectively). CONCLUSIONS: A single
MODS culture of a sputum sample offers more rapid and sensitive detection of
tuberculosis and multidrug-resistant tuberculosis than the existing gold-standard
methods used.
PMID- 17035649
TI - A self-regulation program for maintenance of weight loss.
AB - BACKGROUND: Since many successful dieters regain the weight they lose, programs
that teach maintenance skills are needed. We developed a maintenance program
based on self-regulation theory and tested the efficacy of delivering the program
face to face or over the Internet. METHODS: We randomly assigned 314 participants
who had lost a mean of 19.3 kg of body weight in the previous 2 years to one of
three groups: a control group, which received quarterly newsletters (105
participants), a group that received face-to-face intervention (105), and a group
that received Internet-based intervention (104). The content of the programs in
the two intervention groups was the same, emphasizing daily self-weighing and
self-regulation, as was the frequency of contact with the groups. The primary
outcome was weight gain over a period of 18 months. RESULTS: The mean (+/-SD)
weight gain was 2.5+/-6.7 kg in the face-to-face group, 4.7+/-8.6 kg in the
Internet group, and 4.9+/-6.5 kg in the control group, with a significant
difference between the face-to-face group and the control group (2.4 kg; 95%
confidence interval [CI], 0.002 to 10.8; P=0.05). The proportion of participants
who regained 2.3 kg or more over the 18-month period was significantly higher in
the control group (72.4%) than in the face-to-face group (45.7%; absolute
difference, 27%; 95% CI, 14 to 39; P<0.001) or the Internet group (54.8%;
absolute difference, 18%; 95% CI, 5 to 30; P=0.008). Daily self-weighing
increased in both intervention groups and was associated with a decreased risk of
regaining 2.3 kg or more (P<0.001). CONCLUSIONS: As compared with receiving
quarterly newsletters, a self-regulation program based on daily weighing improved
maintenance of weight loss, particularly when delivered face to face.
(ClinicalTrials.gov number, NCT00067145 [ClinicalTrials.gov].)
PMID- 17035650
TI - Chronic health conditions in adult survivors of childhood cancer.
AB - BACKGROUND: Only a few small studies have assessed the long-term morbidity that
follows the treatment of childhood cancer. We determined the incidence and
severity of chronic health conditions in adult survivors. METHODS: The Childhood
Cancer Survivor Study is a retrospective cohort study that tracks the health
status of adults who received a diagnosis of childhood cancer between 1970 and
1986 and compares the results with those of siblings. We calculated the
frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A
severity score (grades 1 through 4, ranging from mild to life-threatening or
disabling) was assigned to each condition. Cox proportional-hazards models were
used to estimate hazard ratios, reported as relative risks and 95% confidence
intervals (CIs), for a chronic condition. RESULTS: Survivors and siblings had
mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to
56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had
at least one chronic condition; 27.5% had a severe or life-threatening condition
(grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor,
as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life
threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors,
the cumulative incidence of a chronic health condition reached 73.4% (95% CI,
69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of
42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening
conditions or death due to a chronic condition. CONCLUSIONS: Survivors of
childhood cancer have a high rate of illness owing to chronic health conditions.
PMID- 17035651
TI - External-beam radiotherapy for localized prostate cancer.
PMID- 17035652
TI - Images in clinical medicine. Medical mystery--visual-field defect.
PMID- 17035653
TI - Case records of the Massachusetts General Hospital. Case 31-2006. A 15-year-old
girl with severe obesity.
PMID- 17035654
TI - Alzheimer's disease--clinical trials and the logic of clinical purpose.
PMID- 17035655
TI - Rapid detection of tuberculosis and drug-resistant tuberculosis.
PMID- 17035656
TI - Amyotrophic lateral sclerosis--are microglia killing motor neurons?
PMID- 17035657
TI - Doxycycline for the prevention of tick-borne relapsing fever.
PMID- 17035658
TI - The underrecognized burden of influenza.
PMID- 17035659
TI - Hospital volume and outcomes of mechanical ventilation.
PMID- 17035660
TI - Intensive care of patients with HIV infection.
PMID- 17035661
TI - Long-term raloxifene in a woman at high risk for breast cancer.
PMID- 17035662
TI - Roadmap or roadkill: a pharmacologist's analysis of the NIH Molecular Libraries
Initiative.
PMID- 17035663
TI - Unraveling the structure of the variola topoisomerase IB-DNA complex: a possible
new twist on smallpox therapy.
AB - Smallpox is a serious and highly contagious disease that is caused by the variola
virus. It is one of the most severe infectious human diseases known, with
mortality rates as high as 30%. A successful worldwide vaccination program led to
the eradication of smallpox in 1980. However, the high transmission rate of
variola virus, coupled with the deadly nature of smallpox, makes this virus a
potentially devastating weapon for bioterrorism. Currently, there is no specific
treatment for smallpox. However, a recent article on the structure of a variola
topoisomerase IB-DNA complex provides an intriguing starting point for the
rational design of drugs with potential activity against smallpox.
PMID- 17035664
TI - Prospects for an anti-ghrelin vaccine to treat obesity.
AB - In the battle to treat the pandemic of obesity, one therapeutic strategy is to
block endogenous signals that stimulate appetite and control body weight. One
such molecule is ghrelin, a gut peptide that is the only known orexigenic hormone
and is a likely contributor to mealtime hunger. The relative importance of
ghrelin in long-term body-weight regulation (and thus its promise as an anti
obesity target) is uncertain, however, because genetic and pharmacologic blockade
of ghrelin signaling have yielded variable results to date. Using a novel
approach of vaccinating rats against their own ghrelin, Zorilla et al. report
that animals with high ghrelin-specific antibody titers displayed restricted body
weight, without evidence of non-specific inflammation following the vaccine.
These results favor a meaningful role for ghrelin in energy homeostasis, hinting
at a possible new anti-obesity approach. More broadly, the work of Zorilla et al.
supports the feasibility of vaccinations directed against specific autologous
targets--immunopharmacotherapy that could potentially be developed to target a
wide array of medical conditions.
PMID- 17035665
TI - Immunodeficiency is a tough nut to CRAC: the importance of calcium flux in T cell
activation.
AB - Severe Combined Immunodeficiency (SCID) is a rare primary immunodeficiency
disease often characterized by a block in T cell development, which may also
affect the normal development of B cells and NK cells. Several different
mutations are known to give rise to SCID, and multiple genes are involved.
Consequently, there are several different forms of SCID, which can be classified
according to the metabolic and cellular defects that impede normal lymphocyte
function. The two most prevalent forms of SCID are X-linked SCID and adenosine
deaminase (ADA) deficiency SCID, together accounting for approximately 70-80% of
disease cases. Other genetic abnormalities associated with this syndrome range
from defective T cell receptor rearrangement to non-functional signaling
molecules. Recently, a new genetic defect has been described in which mutations
in a key component of Ca(2+) release activated-channels (CRAC) result in T
lymphocyte malfunction.
PMID- 17035666
TI - Salvinorin A: from natural product to human therapeutics.
AB - The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the
Sage family that has been used for divination and shamanism by the Mazatecs. Over
the past decade or so, S. divinorum has been increasingly used recreationally.
The neoclerodane diterpene salvinorin A is the active component of S. divinorum,
and recently, the kappa opioid receptor (KOR) has been identified, in vitro and
in vivo, as its molecular target. The discovery of KOR as the molecular target of
salvinorin A has opened up many opportunities for drug discovery and drug
development for a number of psychiatric and non-psychiatric disorders.
PMID- 17035667
TI - SAR by NMR: putting the pieces together.
AB - It has been nearly ten years since the introduction of SAR by NMR and the advent
of fragment-based drug design. During this time, we have gained a tremendous
amount of knowledge about protein druggability, the limits of chemical diversity,
and crafting high-affinity ligands from low molecular weight, weakly binding
leads. This review will describe the concept of fragment-based drug design,
discuss why it works, and illustrate the power of the approach with two case
studies on the design of potent inhibitors of matrix metalloproteinases and Bcl-2
family proteins.
PMID- 17035668
TI - Measuring the reinforcing strength of abused drugs.
AB - Animal models for human diseases are highly valued for their utility in
developing new therapies. Animals have long provided suitable platforms for the
development of innovative surgical procedures and for the study of disease states
that are relatively easy to produce in otherwise healthy animals, such as
diabetes or hypertension. Increasingly, new strains of animals susceptible to
common human illnesses are being introduced into medical research, promising new
inroads into the treatment of a variety of organic disorders. Despite these
advances in model development, psychiatric disorders, by and large, remain among
the hardest to induce experimentally, and the search for reasonable animal
procedures to study diseases of the mind is an ongoing challenge for experimental
biologists. An exception to this limitation, however, comes in the study of drug
abuse. Major developments in this area of research over the last several decades
have steadily advanced our ability to identify pharmacological, genetic, and
environmental determinants that contribute to the development of drug dependence
and addictive behavior.
PMID- 17035669
TI - Antimicrobial mouthrinses and the management of periodontal diseases.
Introduction to the supplement.
AB - BACKGROUND: Periodontal diseases are complex disorders that have been associated
with multiple risk factors. These disorders are triggered by the accumulation of
dental plaque, and the clinical signs are caused by the resultant inflammatory
and immune responses. Tissue destruction that defines periodontitis has been
linked to excessive production of proinflammatory molecules including matrix
metalloproteinases, interleukin-1 beta and prostaglandin E(2). Important risk
factors for periodontitis can be grouped into four categories: microbial,
systemic, behavioral and local. These risk factors can be considered modifiable
or unmodifiable. Controlling risk factors is important in the management of
chronic diseases and is a valid strategy for controlling periodontal diseases.
Limiting the accumulation of dental plaque is an important part of controlling
the development and progression of periodontal diseases. By adhering to a daily
oral hygiene regimen that includes brushing, flossing and rinsing, patients play
an essential role in disease management. CONCLUSION: Patients play an important
role in controlling the oral microbial biofilm that is essential to the
initiation, development and progression of periodontal diseases. A daily oral
hygiene regimen that includes the use of an antimicrobial mouthrinse can modify
patients' microbial risk of developing periodontal disease. CLINICAL
IMPLICATIONS: Patients can help reduce their risk of developing periodontal
disease by controlling the accumulation of plaque. This can be accomplished, in
part, by adhering to a daily oral hygiene regimen that includes brushing,
flossing and using an antimicrobial mouthrinse.
PMID- 17035670
TI - Managing the complexity of a dynamic biofilm.
AB - BACKGROUND: This article provides an overview of the history of oral
microbiology, a discussion of dental plaque as both a microbial community and a
biofilm, and a review of the measures available to control the oral microflora.
TYPES OF STUDIES REVIEWED: The authors reviewed the literature related to oral
microbiology and associated infectious diseases. They also examined articles that
detailed the structure and physiology of biofilms, including dental plaque
biofilms. CONCLUSIONS: Biofilms cannot be eliminated. The pathogenic nature of
the dental plaque biofilm can be diminished in the oral cavity by reducing the
bioburden and effectively maintaining a normal oral flora via oral hygiene
procedures that include daily toothbrushing, flossing and rinsing with an
antimicrobial mouthrinse. An oral hygiene regimen that includes rinsing with an
antimicrobial mouthrinse is a practical approach to the prevention and management
of periodontal diseases. This strategy may have wider benefits when the link
between periodontal disease and certain systemic diseases is considered. CLINICAL
IMPLICATIONS: An effective oral hygiene regimen can help control dental plaque
biofilm and associated periodontal diseases.
PMID- 17035671
TI - The rationale for the daily use of an antimicrobial mouthrinse.
AB - BACKGROUND: This article reviews the rationale for incorporating effective
antimicrobial mouthrinses into a daily oral hygiene regimen along with mechanical
plaque control methods. TYPES OF STUDIES REVIEWED: The author reviewed studies
demonstrating the essential etiologic role of a pathogenic dental plaque biofilm
in the development of gingivitis, as well as studies indicating that most people
fail to maintain a level of mechanical plaque control sufficient to prevent
disease. In addition, he did a brief review of studies of oral microbial ecology
that identified the oral mucosal tissues as a reservoir of bacteria that colonize
tooth surfaces, and he summarized six-month clinical studies of marketed
antimicrobial mouthrinse ingredients and products. CONCLUSIONS: There is a
twofold rationale for daily use of antimicrobial mouthrinses: first, given the
inadequacy of mechanical plaque control by the majority of people, as a component
added to oral hygiene regimens for the control and prevention of periodontal
diseases; second, as a method of delivering antimicrobial agents to mucosal sites
throughout the mouth that harbor pathogenic bacteria capable of recolonizing
supragingival and subgingival tooth surfaces, thereby providing a complementary
mechanism of plaque control. The efficacy of several mouthrinse ingredients and
products is supported by published six-month clinical trials. CLINICAL
IMPLICATIONS: The daily use of an effective antiplaque/antigingivitis
antimicrobial mouthrinse is well-supported by a scientific rationale and can be a
valuable component of oral hygiene regimens.
PMID- 17035673
TI - Risk assessment and management of periodontal disease.
AB - BACKGROUND: As our understanding of periodontal diseases has increased, it has
become clear that certain risk factors are associated with the diseases'
incidence, severity and progression. This article focuses on the role of risk
assessment and disease management in improving patient outcomes, both in the
general population and in specific population groups with an increased risk of
developing periodontal disease or with associated comorbidities. TYPES OF STUDIES
REVIEWED: The author reviewed literature related to the efficacy of risk
assessment and periodontal disease management in improving clinical outcomes. In
addition, he examined studies demonstrating a link between periodontal disease
and specific patient populations and other comorbidities. CONCLUSIONS: Risk
assessment can help predict a patient's risk of developing periodontal disease
and improve clinical decision making. In turn, patient adherence to a self-care
oral health regimen is a key component to successful periodontal disease
management. CLINICAL IMPLICATIONS: The clinical practice of risk assessment may
reduce the need for complex periodontal therapy, improve patient outcomes and
ultimately reduce oral health care costs. Patients are encouraged to become
actively involved in periodontal disease management by following a daily three
step regimen of brushing, flossing and rinsing with an antimicrobial mouthrinse.
PMID- 17035672
TI - Antimicrobial mouthrinse as part of a comprehensive oral care regimen. Safety and
compliance factors.
AB - BACKGROUND: Antimicrobial mouthrinses often are used as part of daily oral care
to reduce plaque and gingivitis. Although several safety factors have been
associated with long-term use of alcohol-containing mouthrinses, numerous studies
support the safety of these products in daily care. Patient compliance with daily
rinsing is important for successful outcomes. TYPES OF STUDIES REVIEWED: The
authors reviewed studies relating to the safety and efficacy of alcohol
containing mouthrinses, as well as studies indicating that most patients fail to
comply with oral health care recommendations. The authors also reviewed a
behavioral change theory and applied it to oral health care. CONCLUSIONS: Alcohol
containing antimicrobial mouthrinses are safe and effective as part of a daily
oral care regimen to prevent or minimize periodontal disease. However, many
patients do not comply with instructions on how to use them. CLINICAL
IMPLICATIONS: Antimicrobial mouthrinses are safe and effective, and when used in
conjunction with brushing and flossing, they are an important method of reducing
plaque and gingivitis. To improve compliance, dental health care professionals
should adapt oral health care recommendations to fit patients' specific needs.
PMID- 17035674
TI - A role of lipin in human obesity and insulin resistance: relation to adipocyte
glucose transport and GLUT4 expression.
AB - The mouse lipin gene, Lpin1, is important for adipose tissue development and is a
candidate gene for insulin resistance. Here, we investigate the adipose tissue
expression levels of the human LPIN1 gene in relation to various clinical
variables as well as adipocyte function. LPIN1 gene expression was induced at an
early step in human preadipocyte differentiation in parallel with peroxisome
proliferator-activated receptor gamma. Lipin mRNA levels were higher in fat cells
than in adipose tissue segments but showed no difference between subcutaneous and
omental depots. Moreover, LPIN1 expression levels were reduced in obesity,
improved following weight reduction in obese subjects, and were downregulated in
women with the metabolic syndrome. With respect to adipocyte function, adipose
LPIN1 gene expression was strongly associated with both basal and insulin
mediated subcutaneous adipocyte glucose transport as well as mRNA levels of
glucose transporter 4 (GLUT4). We show that body fat accumulation is a major
regulator of human adipose LPIN1 expression and suggest a role of LPIN1 in human
preadipocyte as well as mature adipocyte function.
PMID- 17035675
TI - High frequency of partial SPAST deletions in autosomal dominant hereditary
spastic paraplegia.
AB - BACKGROUND: Hereditary spastic paraplegia (HSP) is a genetically heterogeneous
neurodegenerative disease. The most frequent cause of autosomal dominant HSP is
mutation of SPAST (SPG4 locus), but additional pedigrees remain mutation negative
by conventional screening despite linkage to SPG4. OBJECTIVE: To determine the
frequency of genomic copy number aberrations of SPAST in autosomal dominant HSP.
METHODS: We developed and validated a multiplex ligation-dependent probe
amplification assay targeting SPAST and SPG3A, another gene frequently involved
in autosomal dominant HSP. In a multicenter study we subsequently investigated 65
index patients with autosomal dominant HSP, all of whom had previously been
screened negative for SPAST mutations. Independent secondary samples, additional
family members, and cDNA were analyzed to confirm positive findings. RESULTS:
Aberrant MLPA profiles were identified in 12 cases (18%). They exclusively affect
SPAST, represent deletions, segregate with the disease, and are largely pedigree
specific. Internal SPAST deletions entail expression of correspondingly shortened
transcripts, which vary in stability. Age at onset in SPAST deletion carriers
does not differ from that associated with other SPAST mutations. CONCLUSIONS:
Partial SPAST deletions, but not SPAST amplifications and SPG3A copy number
aberrations, represent an underestimated cause of autosomal dominant hereditary
spastic paraplegia. Partial SPAST deletions are likely to act via
haploinsufficiency.
PMID- 17035676
TI - Phase II trial of pirfenidone in adults with neurofibromatosis type 1.
AB - We performed an open-label phase II trial of oral pirfenidone in 24 patients with
neurofibromatosis type 1 (NF1). Tumors were monitored by three-dimensional MRI.
At the end of treatment, four patients had a decrease in tumor volume by 15% or
more, three had tumor progression, and 17 remained stable. Pirfenidone warrants
further investigation in NF1, which has until now lacked an effective control
therapy.
PMID- 17035677
TI - Metabolite profiling in blood plasma.
AB - Metabolite profiling has been established as a multiparallel strategy for
relative quantification of a mixture of compounds or compound classes using
chromatography and universal detection technologies (gas chromatography-mass
spectrometry [GC-MS], liquid chromatography-MS). Despite its origins dating back
to the late 1960s, it was only in the 1980s that its use was acknowledged to
diagnose metabolic disorders in men, especially for rapid screening of inborn
errors. Even faster electrospray ionization-MS/MS screening methods replaced
longish chromatographic methods, and method development had stopped despite its
potential use for other, less imminent diseases such as likelihood assessments of
type II diabetes mellitus or cardiovascular risk factor evaluation. In addition
to its diagnostic use, profiling blood samples can be employed to investigate
specific biochemical responses. The broader scope of analysis outweighs the
disadvantages by taking compromises in method development and the reduced
accuracy for specific metabolites. This chapter exemplifies the strategies in
metabolite profiling by GC-MS. It gives experimental details on basic steps like
blood plasma withdrawal, storage, protein precipitation, extraction,
concentration, derivatization, data acquisition, raw data processing, and result
data tranformation. A major difference to profiling plant tissues is that no
fractionation step is utilized, enabling the analysis of primary metabolites like
sugars and amino acids concomitant with lipids such as sterols and free fatty
acids.
PMID- 17035678
TI - Nonsupervised construction and application of mass spectral and retention time
index libraries from time-of-flight gas chromatography-mass spectrometry
metabolite profiles.
AB - Gas chromatography-mass spectrometry (GC-MS) is routinely applied to the
metabolite profiling of biological samples. Time-of-flight (TOF)-GC-MS metabolite
profiling is based on highly reproducible electron impact ionization. Single
chromatograms may comprise 200-1000 mass spectral components. The nature and
composition of these mass spectral components depend on the choice of metabolite
extraction, type of biological sample, and experimental condition. The components
represent mass spectral tags (MSTs) of volatile metabolites or metabolite
derivatives. Identification of MSTs is the major challenge in GC-MS metabolite
profiling. We describe methods suitable for the automated construction of mass
spectral and retention time index databases from large sets of TOF-GC-MS
profiles. Application of these libraries for automated identification by pure
reference compounds and classification of hitherto unidentified MSTs from
biological sources is demonstrated.
PMID- 17035679
TI - Metabolomic profiling of natural volatiles: headspace trapping: GC-MS.
AB - Plants are a fabulously rich source of naturally volatile metabolites, which are
derived from a range of contrasting biochemical pathways (e.g., mono-, di-, and
sesquiterpenoids, benzoates, alcohols, esters). Such volatiles may immediately be
released from the plant or they may be stored, e.g., in glycosylated form for
release later "on demand." Certain roles for these molecules have already been
determined in that they can function as attractants (e.g., to pollinators, seed
dispersers, and others) or as protectants (repellants, pathogen inhibitors, and
so on). The flavor and fragrance of plant materials to humans and other animals
are also, to a great extent, determined by natural volatiles. Other more
sophisticated roles have also been elucidated where plant volatiles have been
shown to be involved either as signal molecules to attract the predators of
damaging herbivorous insects or potentially even as signal molecules warning
other plants of imminent danger. As such, detailed knowledge of these components
can be valuable in relation to breeding crop varieties for enhanced product
quality or for achieving improved resistance to pathogens and insects.
Furthermore, knowledge of the metabolites can result in a corresponding knowledge
of the genes responsible for their synthesis and this can lead to dedicated
strategies for their in vitro production through, e.g., reverse genetics in
heterologous microbial expression systems in fermentors for the production of
high-value fine chemicals. Various analytical techniques based on gas
chromatography-mass spectrometry have been devised for the analysis of this
complex group of metabolites. Two of these key methods are detailed in this
chapter.
PMID- 17035680
TI - Integrative profiling of metabolites and proteins: improving pattern recognition
and biomarker selection for systems level approaches.
AB - Methods such as mRNA expression profiling have provided a vast amount of genomic
and transcriptomic information about plants and other organisms. However, there
is explicit indication that considerable metabolic control is executed on the
metabolite and on the protein level including protein modifications, thereby
constituting the phenotypic plasticity. Consequently, the analysis of the
molecular phenotype demands the step toward mass spectrometry (MS)-based
postgenomic techniques such as metabolomics and proteomics. This chapter
describes a straightforward protocol for simultaneously extracting metabolites
and proteins from the same biological sample in preparation for MS analysis.
Furthermore, protocols for profiling polar metabolites using gas chromatography
time-of-flight MS and for shotgun proteomics using liquid chromatography-MS are
discussed. A practical course is laid out that outlines all the basic steps, from
harvesting to data analysis. These steps enable the correlative study of
metabolite and protein dynamics with minimal technical variation. Biological
variability of independent samples is exploited for variance analysis and pattern
recognition.
PMID- 17035681
TI - Integrating profiling data: using linear correlation to reveal coregulation of
transcript and metabolites.
AB - Recent advances in the medical and biological sciences have been characterized by
a major paradigm shift from reductionism to integrated and holistic systems
approaches. Such approaches are characterized at the experimental level by the
multiparallel analysis of a multitude of parameters of a given biological system
at a range of different molecular levels, following the systematic perturbation
of the system in question. Although a multitude of studies have been carried out
to assess the transcript, protein, and metabolite complements of cells under
various conditions, to date, few have been attempted that encompass the profiling
of more than one of these entities. In this chapter, we describe combined
analysis of data obtained from transcript and metabolic profiling, and detail
advantages of using both approaches in parallel.
PMID- 17035682
TI - Visualization and analysis of molecular data.
AB - This chapter provides an overview of visualization and analysis techniques
applied to large-scale datasets from genomics, metabolomics, and proteomics. The
aim is to reduce the number of variables (genes, metabolites, or proteins) by
extracting a small set of new relevant variables, usually termed components. The
advantages and disadvantages of the classical principal component analysis (PC A)
are discussed and a link is given to the closely related singular value
decomposition and multidimensional scaling. Special emphasis is given to the
recent trend toward the use of independent component analysis, which aims to
extract statistically independent components and, therefore, provides usually
more meaningful components than PCA. We also discuss normalization techniques and
their influence on the result of different analytical techniques.
PMID- 17035683
TI - A gentle guide to the analysis of metabolomic data.
AB - Modern molecular biology crucially relies on computational tools to handle and
interpret the large amounts of data that are generated by high-throughput
measurements. To this end, much effort is dedicated to devise novel sophisticated
methods that allow one to integrate, evaluate, and analyze biological data.
However, prior to an application of specifically designed methods, simple and
well-known statistical approaches often provide a more appropriate starting point
for further analysis. This chapter seeks to describe several well-established
approaches to data analysis, including various clustering techniques,
discriminant function analysis, principal component analysis, multidimensional
scaling, and classification trees. The chapter is accompanied by a webpage,
describing the application of all algorithms in a ready-to-use format.
PMID- 17035684
TI - Capillary electrophoresis-mass spectrometry for metabolomics.
AB - A new approach for the comprehensive and quantitative analysis of charged
metabolites by capillary electrophoresis-mass spectrometry (CE-MS) is described.
Metabolites are first separated by CE based on charge and size, and then
selectively detected using MS by monitoring ions over a large range of m/z
values. This technique enables the simultaneous determination of over 1000
charged species, and it can readily be applied to various types of biological
samples originating from bacteria, plants, mammals, body fluids, and others. This
chapter highlights detailed practical procedures for using this technology.
PMID- 17035685
TI - Application of liquid chromatography-mass spectrometry analysis in metabolomics:
reversed-phase monolithic capillary chromatography and hydrophilic chromatography
coupled to electrospray ionization-mass spectrometry.
AB - Analysis of the entire metabolome as the sum of all detectable components in the
sample rather than analysis of each individual metabolite is performed by the
metabolomics approaches. To monitor in parallel hundreds or even thousands of
metabolites, high-throughput techniques are required that enable screening for
relative changes rather than absolute concentrations of compounds. Most
analytical techniques for profiling small molecules consist of gas chromatography
(GC) or high-performance liquid chromatography (HPLC) coupled to mass
spectrometry. HPLC separations are better suited for the analysis of labile and
high molecular weight compounds, and for the analysis of nonvolatile polar
compounds in their natural form. Although GC- and HPLC-based profiling techniques
are not truly quantitative, the compounds detecting and employing the acceptable
standards may compare their relative amounts. We have demonstrated that reversed
phase monolithic capillary chromatography and hydrophilic chromatography can be
successfully applied for sufficient plant crude extracts separations and
metabolomics studies.
PMID- 17035686
TI - High-performance liquid chromatography separations coupled with coulometric
electrode array detectors: a unique approach to metabolomics.
AB - Metabolomics is the systematic and theoretically comprehensive study of the small
molecules that comprise a biological sample, e.g., sera or plasma. The primary
analytical tools used in metabolomics are nuclear magnetic resonance and mass
spectroscopy. We here address a different tool, high-performance liquid
chromatography (HPLC) separations coupled with coulometric electrode array
detection. This system has unique advantages, notably sensitivity and high
quantitative precision, but also has unique limitations, such as obtaining little
structural information on the metabolites of interest and limited scale-up
capacity. The system also only detects redox-active compounds, which can be
either a benefit or a detriment, depending on the experimental goals and design.
Here, we discuss the characteristics of this HPLC/coulometric electrode array
system in the context of metabolomics, and then present the method as practiced
in our groups.
PMID- 17035687
TI - Determination of metabolic flux ratios from 13C-experiments and gas
chromatography-mass spectrometry data: protocol and principles.
AB - Network topology is a necessary fundament to understand function and properties
of microbial reaction networks. A valuable method for experimental elucidation of
metabolic network topology is metabolic flux ratio analysis, which quantifies the
relative contribution of two or more converging pathways to a given metabolite.
It is based on 13C-labeling experiments, gas chromatography-mass spectrometry
analysis, and probabilistic equations that relate mass distributions in
proteinogenic amino acids to pathway activity. Here, we describe the protocol for
sample generation and illustrate the principles underlying the calculation of
metabolic flux ratios with three examples. These principles are also implemented
in the publicly available software FiatFlux, which directly calculates flux
ratios from the mass spectra of amino acids.
PMID- 17035688
TI - Understanding the roadmap of metabolism by pathway analysis.
AB - The theoretical investigation of the structure of metabolic systems has recently
attracted increasing interest. In this chapter, the basic concepts of metabolic
pathway analysis are described and various applications are outlined. In
particular, the concepts of nullspace and elementary flux modes are explained.
The presentation is illustrated by a simple example from tyrosine metabolism and
a system describing lysine production in Corynebacterium glutamicum. The latter
system gives rise to 37 elementary modes, 36 of which produce lysine with
different molar yields. The examples illustrate that metabolic pathway analysis
is a useful tool for better understanding the complex architecture of
intracellular metabolism, for determining the pathways on which the molar
conversion yield of a substrate-product pair under study is maximal, and for
assigning functions to orphan genes (functional genomics). Moreover, problems
emerging in the modeling of large networks are discussed. An outlook on current
trends in the field concludes the chapter.
PMID- 17035689
TI - Revealing the metabolome of animal tissues using 1H nuclear magnetic resonance
spectroscopy.
AB - The measurement of tissue-specific metabolic fingerprints can be of particular
interest when investigating disease processes, mechanisms of toxicity, or when
knowledge of the metabolic interactions between different organs is required.
This chapter presents several optimized protocols for the extraction of
metabolites from animal tissues, their analysis by 1H nuclear magnetic resonance
(NMR) spectroscopy, and the subsequent spectral preprocessing required for an NMR
based metabolomics experiment. First, the three critical steps in the preparation
of tissue extracts for NMR analysis are described, including both a perchloric
acid protocol for the extraction of polar metabolites, and a methanol:chloroform
protocol for extraction of polar and lipophilic metabolites. Then a series of NMR
experiments are described including a standard one-dimensional (1D) 1H NMR study,
a 1D 1H Carr-Purcell-Meiboom-Gill spin-echo experiment, and a two-dimensional 1H
1H J-resolved NMR experiment. The advantages and limitations of each experiment
for metabolomics research are discussed. Analysis of the resulting NMR datasets
is typically conducted in two phases comprising "low level" spectral
preprocessing and "high level" multivariate analysis. NMR spectral preprocessing
is a critical step that converts raw NMR spectra into an appropriate data format
for multivariate analysis. A detailed protocol for preprocessing NMR data, using
ProMetab software, is presented. Because a plethora of algorithms exist for
multivariate analyses, which can be used to construct classification models or
for biomarker discovery, this is beyond the scope of the current chapter.
PMID- 17035690
TI - Nuclear magnetic resonance metabonomics: methods for drug discovery and
development.
AB - Nuclear magnetic resonance (NMR)-based metabonomics is gaining popularity in drug
discovery and development and in academia in a variety of settings, ranging from
toxicology, preclinical, and clinical approaches to nutrition research, studies
on microorganisms, and research on plants. This chapter focuses on the basic
steps in a metabonomics study and emphasizes experience and lessons learned in
our lab where we focused on metabonomic analyses of plant extracts, cell lines,
and a variety of animal tissues and biofluids. We emphasize that a comprehensive
and suitable study design is pivotal for a correct biological interpretation of
the results, as well as highly controlled experimental conditions. Sample
preparation and NMR protocols are detailed for a wide range of sample types. We
discuss alternative data processing strategies and considerations for a general
data analysis approach, paying particular attention to the statistical
interpretation and validation of the results while also highlighting approaches
to avoid possible pitfalls resulting from systematic and random errors. A
tutorial written for the R statistical package and other small utilities are
available from the authors upon request.
PMID- 17035691
TI - Practical aspects of uniform stable isotope labeling of higher plants for
heteronuclear NMR-based metabolomics.
AB - Analytical methods for probing plant metabolism are taking on new significance in
the era of functional genomics, metabolomics, and systems biology. Nuclear
magnetic resonance (NMR) is becoming a key technology in plant metabolomics.
Stable isotope labeling of cultured cells and higher organisms has been
especially promising in that it allows the use of advanced heteronuclear NMR
methodologies through a combination of in vivo and in vitro measurements. This
new approach provides much better resolution of the metabolite mixture signals in
the multidimensional NMR spectra than does the conventional one-dimensional 1H
NMR previously used in plant metabolomics. In this chapter, we describe the
practical aspects of two key NMR technologies: uniform stable labeling of plants
and in vitro heteronuclear NMR.
PMID- 17035692
TI - Hospital admissions associated with traumatic brain injury in the US Army during
peacetime: 1990s trends.
AB - INTRODUCTION: This paper examines 10-year trends in traumatic brain injury (TBI)
related hospitalization rates for active duty US Army personnel in the 1990s. It
does this within the context of various factors, including enhanced injury
prevention policies and changed hospital admission practices, that may have
affected TBI hospitalization rates. It also compares TBI hospitalization rates in
the Army to those from an age-comparable segment of the US civilian population
over this time period. METHODS: Crude (unadjusted) incidence rates for all active
duty US Army personnel hospitalized with a TBI diagnosis from fiscal years (FY)
1990 to 1999 were calculated. Once the trends were identified, the percentage
change in the overall rate, as well as the rates for different TBI severity
levels, and in-hospital deaths from FY1990 and FY1999 were analyzed. Changes in
age- and gender-specific rates as well as crude rates for cases with and without
other injuries and cases treated in military and civilian hospitals were also
analyzed. Rate ratios were used to compare aggregated 5-year TBI hospitalization
rates in the Army to rates for civilians 17-49 years of age during the following
time periods: 1990-1994 and 1995-1999. The rates used in the comparison were
adjusted to control for differences in age and gender. RESULTS: The overall
incidence of TBI-related hospitalization in the Army decreased 75% from FY1990 to
FY1999. The rates for all TBI severity levels decreased, but the rate for mild
TBI decreased more than the rates for moderate and severe TBI. The rate of in
hospital deaths from TBI also decreased. Rates decreased similarly for males and
females, across all age groups, as well as for cases with and without other
injuries. TBI rates decreased for Army personnel treated in military hospitals
but changed minimally for Army personnel treated in civilian hospitals. The
Army's TBI hospitalization rates were generally higher than civilian rates in the
early 1990s but by the late 1990s, most of the Army's rates were lower than or
equal to the civilian rates. CONCLUSIONS: The incidence of TBI-related
hospitalization in the active duty US Army decreased markedly (75%) during the
1990s. As a result, most of the Army's TBI hospitalization rates were lower than
civilian rates by the late 1990s. Effective injury prevention and changes in the
Army population were two of the factors that likely contributed to the decrease
in rates for all TBI severity levels, while changes in hospital admission
practices likely contributed to the disproportionate decrease in the Army's rates
for mild TBI.
PMID- 17035693
TI - Descriptive epidemiology of spinal muscular atrophy type I in Estonia.
AB - Spinal muscular atrophy is the second most frequent autosomal-recessive disorder
in Europeans. There are no published epidemiological data on SMA in Estonia and
other Baltic countries. The aim of this study was to estimate the incidence of
SMA I in Estonia. All patients with SMA I diagnosed between January 1994 and
December 2003 were included in the study. The diagnosis was established on the
basis of neurological evaluation, ENMG findings, molecular studies and muscle
biopsy. PCR and restriction enzyme analysis was used to detect the homozygous
deletion of the SMN1 gene. A total of 9 cases of SMA I were identified during
this 10-year period. The incidence of SMA I in Estonia is 1 in 14,400 live
births, which is similar to the result from Hungary but lower than average
incidence in the world. Only one of the patients was female. Typical SMN1 gene
deletion was found in all cases.
PMID- 17035694
TI - Decision rules guiding the clinical diagnosis of Alzheimer's disease in two
community-based cohort studies compared to standard practice in a clinic-based
cohort study.
AB - We developed prediction rules to guide the clinical diagnosis of Alzheimer's
disease (AD) in two community-based cohort studies (the Religious Orders Study
and the Rush Memory and Aging Project). The rules were implemented without
informant interviews, neuroimaging, blood work or routine case conferencing.
Autopsies were performed at death and the pathologic diagnosis of AD made with a
modified version of the Consortium to Establish a Registry for Alzheimer's
Disease (CERAD) criteria. We compared the positive predictive value of the
clinical diagnosis in the two community-based studies to the positive predictive
value of the clinical diagnosis of AD made by standard clinical practice in a
clinic-based cohort study using AD pathology as the gold standard. Of 306 clinic
cases with probable AD, 286 (93.5%) met CERAD neuropathologic criteria for AD;
the results were comparable for those with possible AD (51 of 54, 94.4%). Of 141
study subjects with probable AD, 130 (92.2%) met CERAD neuropathologic criteria
for AD; the results were lower but acceptable for those with possible AD (26 of
37, 70.3%). The results were similar in secondary analyses using alternate
neuropathologic criteria for AD. The clinical diagnosis of AD can be made in
community-based studies without the use of informant interviews, neuroimaging,
blood work or routine case conferencing. This approach holds promise for reducing
the operational costs of epidemiologic studies of aging and AD.
PMID- 17035695
TI - 'The success of the mentee is the mentor's ultimate reward'. An interview with
Dr. Michael L. Steer by Martin E. Fernandez-Zapico.
AB - In this interview, Dr. Michael Steer shares his life experience in pancreatic
research, discusses the importance of mentorship and gives advice to young
investigators starting in this field. Dr. Michael Steer is a world-renown
investigator who has made an extraordinary contribution to the understanding of
pancreatic physiology. His achievements in the field of acute pancreatitis were
the foundation for the characterization of the cellular basis for this disease.
PMID- 17035698
TI - Report of the 15th European Stroke Conference, Brussels, May 16-19, 2006.
PMID- 17035697
TI - A randomized controlled trial of oral versus intravenous iron in chronic kidney
disease.
AB - BACKGROUND: It is unknown whether intravenous iron or oral iron repletion alone
can correct anemia associated with chronic kidney disease (CKD). We conducted a
randomized multicenter controlled trial in adult anemic, iron-deficient non
dialysis CKD (ND-CKD) patients (>or=stage 3) not receiving erythropoiesis
stimulating agents (ESAs). METHODS: The participants were randomized to receive
either a sodium ferric gluconate complex (intravenous iron) 250 mg i.v. weekly x
4 or ferrous sulfate (oral iron) 325 mg t.i.d. x 42 days. Hemoglobin (Hgb),
ferritin and transferrin saturation (TSAT) were measured serially, and the Kidney
Disease Quality of Life (KDQoL) questionnaire was administered on days 1 and 43.
The primary outcome variable was change from baseline (CFB) to endpoint in Hgb
values. RESULTS: Seventy-five patients were analyzed (intravenous iron n = 36,
oral iron n = 39). CFB in Hgb was similar in the two groups (intravenous iron 0.4
g/dl vs. oral iron 0.2 g/dl, p = n.s.). However, the increase in Hgb was only
significant with intravenous iron (p < 0.01). In comparison to oral iron,
intravenous iron achieved greater improvements in ferritin (232.0 +/- 160.8 vs.
55.9 +/- 236.2 ng/ml, p < 0.001) and TSAT (8.3 +/- 7.5 vs. 2.9 +/- 8.8%, p =
0.007). Intravenous iron caused greater improvements in KDQoL scores than oral
iron (p < 0.05). The most common side effect reported with intravenous iron was
hypotension, while constipation was more common with oral iron. CONCLUSIONS: Oral
and intravenous iron similarly increase Hgb in anemic iron-depleted ND-CKD
patients not receiving ESAs. Although in comparison to oral iron, intravenous
iron may result in a more rapid repletion of iron stores and greater improvement
in quality of life, it exposes the patients to a greater risk of adverse effects
and increases inconvenience and cost.
PMID- 17035699
TI - Surgical shunt closure via the lumen of an intrahepatic portal aneurysm.
AB - BACKGROUND/AIMS: A surgical shunt closure via the lumen of an intrahepatic portal
aneurysm was successfully performed in a 70-year-old Japanese woman with hepatic
encephalopathy due to hyperammonemia. She had a 4-month history of repeated
hepatic encephalopathy which persisted after treatment with oral medicine. Color
Doppler ultrasonography and computed tomography revealed a cystic peripheral
portal aneurysm, 4 cm in diameter, connecting the posterior branch of the portal
vein to the short hepatic vein in the right lobe. METHODS: While performing the
Pringle maneuver and clamping the inferior vena cava below the liver, the wall of
the portal aneurysm was opened, and the site of inflow from the portal vein and
the site of outflow to the hepatic vein via the lumen of the portal aneurysm were
closed with interrupted sutures. RESULTS: The patient's postoperative course was
uneventful, and she was discharged 12 days after surgery. 12 months after
surgery, she had no recurrence of hyperammonemia or hepatic encephalopathy.
CONCLUSION: Surgical shunt closure via the lumen of a portal aneurysm can be
performed safely, easily, and completely with good vision.
PMID- 17035700
TI - Ectopic pancreas in the ampulla of vater with obstructive jaundice. A case report
and review of literature.
AB - Ectopic pancreas is an uncommon condition and is usually found in the
gastrointestinal tract, such as stomach, duodenum and jejunum. However, ectopic
pancreas in the ampulla of Vater is rare and its clinical presentations may be
similar to periampullary cancer. It is difficult to diagnose preoperatively. We
present such a case where the diagnosis was proven postoperatively. Our patient,
a 51-year-old man, presented with epigastric pain, jaundice, weight loss and
abnormal laboratory data. Imaging study, including abdominal sonography,
abdominal computerized tomography with contrast and endoscopic retrograde
cholangiopancreatography, showed a mass protruding into the ampulla of Vater. The
mass was resected and histological examination revealed an ectopic pancreas. The
patient presented with symptoms of periampullary tumor but the imaging study did
not reveal an obvious lesion for us consider the possibility of ectopic pancreas.
Surgical excision is indicated for symptomatic cases.
PMID- 17035701
TI - Digestive tract schwannoma.
AB - BACKGROUND: Digestive tract schwannomas (DTS) are rare benign mesenchymal tumours
usually affecting females between 30 and 60 years old. METHODS: We
retrospectively reviewed 2 cases of DTS treated at our hospital. The first case
is a 38-year-old female with gastric schwannoma presenting with acute upper
gastro-intestinal bleeding. The second case is a 36-year-old female with
mesenteric schwannoma presenting with chronic right iliac fossa pain. Both
patients underwent surgical resection of the tumour. RESULTS: Histology and
immunohistochemistry revealed the typical appearance of a DTS. CONCLUSION: DTS is
most commonly found in the stomach. It is usually asymptomatic but can present
with variable symptoms. Definitive diagnosis can only be made on the basis of
immunohistochemistry. Surgical resection is the treatment of choice.
PMID- 17035702
TI - Asymptomatic carotid artery stenosis: past, present and future. How to improve
patient selection?
AB - BACKGROUND: The role of carotid endarterectomy (CEA) for asymptomatic carotid
artery stenosis (aCAS) remains a matter of debate. It seems that not only the
degree of stenosis, but also other factors have to be taken in account to improve
patient selection and increase the benefit of CEA for aCAS. METHODS AND RESULTS:
The literature pertaining aCAS was reviewed in order to describe the natural
history, risk of stroke and benefit of CEA for patients with aCAS in regard to
several factors. CONCLUSION: The benefit of CEA for aCAS is low. Current factors
influencing the indication for CEA are severity of stenosis, age, contralateral
disease, stenosis progression to >80%, gender, concomitant operations and life
expectancy. To improve patient selection investigations will concentrate on
plaque characteristics and instability and cerebral hemodynamics and metabolism.
PMID- 17035704
TI - Anesthesia dolorosa caused by penetrating cranial injury.
AB - Anesthesia dolorosa (AD) is an uncommon complication of surgical treatments for
trigeminal neuralgia. Its incidence is around 0.8%. To our best knowledge, AD
caused by a penetrating cranial injury has not been reported previously. We
report the case of a 31-year-old male patient with left-sided neuropathic
keratitis and AD that began 18 years earlier, following a penetrating cranial
injury with a knife to the left postauricular area. The patient was successfully
treated by a carbamazepine and gabapentin combination. In conclusion, penetrating
cranial injury is uncommon but may cause a serious neurologic disturbance. In the
differential diagnosis of AD, a penetrating injury should be kept in mind. In
these cases, treatments should be effective and immediate; otherwise, this may
result in catastrophic consequences such as neurotrophic keratitis and blindness.
Ophthalmologists should be aware of these potential problems.
PMID- 17035703
TI - Longitudinal study of bone and calcium metabolism and fracture incidence in
spinocerebellar degeneration.
AB - Little is known about bone and calcium metabolism and fracture incidence in
spinocerebellar degeneration (SCD) despite frequent falls and immobilization. To
address bone and calcium metabolism and fracture incidence in SCD, we conducted a
10-year prospective study in a cohort of adult patients with SCD. Bone mineral
density (BMD) and serum levels of ionized calcium, parathyroid hormone, 25
hydroxyvitamin D, and pyridinoline cross-linked carboxy-terminal telopeptide of
type I collagen (ICTP) were followed in 110 patients with SCD for 10 years. Age
matched healthy volunteers (n = 110) served as controls. At baseline, the SCD
patients had a low BMD with high levels of serum ionized calcium and ICTP which
correlated with the degree of immobilization (Barthel index). Over 10 years,
serum 25-hydroxyvitamin D decreased to the osteomalacic level (<5 ng/ml), and
calcium and ICTP further increased in accordance with a decreased Barthel index
score. The BMD decreased by 15.2% in men and by 24.6% in women. The incidence of
fractures in the patients was significantly higher as compared with the control
group (men 8/49 vs. 1/42, p = 0.0428; women 16/49 vs. 2/48, p = 0.0026). Over 10
years, the BMD was significantly reduced in the SCD patients, particularly in
women, which increased the risk of a fracture. Vitamin D deficiency due to
sunlight deprivation, increased bone resorption due to immobilization, and
frequent falls are probable causes of osteoporosis and fractures in these
patients. Hypovitaminosis D and increased bone resorption may be corrected
readily by the routine use of vitamin D supplements together with bisphosphonate.
PMID- 17035705
TI - Early pathological changes in the cerebellum of patients with pure cerebellar
syndrome demonstrated by diffusion-tensor imaging.
AB - We evaluated the early pathological changes in patients with sporadic cerebellar
ataxia by measuring fractional anisotropy (FA) values in diffusion tensor MRIs
(DTI). FA and apparent diffusion coefficient (ADC) values were compared in the
brain stem and cerebellum of 5 patients with idiopathic cerebellar ataxia-C and 7
age-matched controls. Patients with sporadic cerebellar ataxia had decreased FA
values in the bilateral cerebellar peduncle and cerebellar hemisphere, but normal
FA values in the basis pontes. Assuming that the loss in FA parallels neuronal
changes, our results suggest that the derangement and altered fiber integrity of
the cerebellum are present regardless of the presence of morphological
alterations on conventional MRI. Therefore, DTI may be superior to conventional
MRI in the evaluation of early pathological changes in patients with sporadic
cerebellar ataxia.
PMID- 17035706
TI - Inclusion body myopathy-like changes in a family with cerebellar atrophy, mental
retardation and abnormal pupils.
PMID- 17035707
TI - Images in clinical medicine: miliary tuberculosis of the brain.
PMID- 17035708
TI - Neurological words. Nosology, nosocomial.
PMID- 17035709
TI - F344 rat liver nonparenchymal cell transplantation can increase the number of
albumin-positive hepatocytes in the liver following hematopoietic reconstitution
in irradiated analbuminemic rats.
AB - The adult liver contains hematopoietic stem cells that can reconstitute the bone
marrow. We tested whether bone marrow cells (BMCs) derived from liver
nonparenchymal cells (LNPCs) can increase the number of hepatocytes within
livers. LNPCs from Fischer 344 rats (F344) were infused into the penile veins of
F344 congenic Nagase's analbuminenic rats (F344alb) immediately after whole-body
irradiation, and the recipients were sacrificed 8 weeks later. Eleven of 15
(73.3%) F344alb that received the LNPC transplantation after irradiation
survived, while only 1 of 8 (12.5%) F344alb that received irradiation alone was
alive after 8 weeks. Normal albumin gene sequences were detected by PCR in BMCs
of the recipient F344alb that received LNPC transplantation after irradiation,
indicating that F344alb bone marrow was reconstituted by F344 LNPCs. Although
single or pairs of albumin-positive (Alb+) hepatocytes were seen in the liver of
untreated F344alb and those with irradiation or LNPC transplantation alone,
clusters consisting of >3 Alb+ hepatocytes were detected in the livers of F344alb
with the LNPC or BMC transplantation after irradiation together with single or
double Alb+ cells. Normal albumin gene sequences were detected by PCR in the DNA
isolated from such Alb+ hepatocyte clusters microdissected from the immunostained
sections. The data indicate that BMCs derived from F344 LNPCs could increase the
number Alb+ hepatocytes within the F344alb liver.
PMID- 17035710
TI - Association of physical activity and the metabolic syndrome in children and
adolescents: CASPIAN Study.
AB - BACKGROUND/AIM: To determine the association of physical activity and the
metabolic syndrome in a large national-representative sample of children.
METHODS: This study was performed in 2003-2004 on 4,811 school students aged 6-18
years, selected by multi-stage random cluster sampling from six provinces in
Iran. We assessed the level of physical activity using a standardized
questionnaire, and categorized it to the tertiles. The metabolic syndrome was
defined based on criteria analogous to those of the Adult Treatment Panel III.
RESULTS: The participants comprised 2,248 boys and 2,563 girls with a mean age of
12.07 +/- 3.2 years. In all age groups, boys were more physically active than
girls. The metabolic syndrome was detected in 14.1% of participants, and its
prevalence was higher in those subjects in the 1st, 2nd and 3rd tertiles of
physical activity, respectively (15.1 vs.14.2 and 13.1%, respectively, p <0.05).
This difference was seen in boys, while no difference was found between girls in
the 2nd and 3rd tertiles of physical activity. Physical activity was linked to a
cluster of factors consisting of high-density lipoprotein-cholesterol and waist
circumference, followed by triglycerides in boys, and of triglycerides, waist
circumference and blood pressure in girls. In both genders, before and after
adjustment for age and body mass index, low levels of physical activity
significantly increased the risk of having the metabolic syndrome [in boys: OR:
1.8, 95% CI: 1.1, 2.1; and in girls, OR: 1.6 (1.1, 1.9)]. CONCLUSION: We found an
association between physical activity and the metabolic syndrome, which was
independent of body mass index and age. Children should be encouraged to have
greater physical activity.
PMID- 17035711
TI - Rate of decline of GFR and progression of vascular disease in type 2 diabetic
patients with diabetic or vascular nephropathy during the last three years before
starting dialysis therapy.
AB - BACKGROUND: The progression of chronic renal insufficiency depends on the type of
primary renal disease and blood pressure (BP) levels. We investigated the rate of
decline of glomerular filtration rate (GFR) during 3 years prior to the start of
dialysis therapy in type 2 diabetic patients with diabetic nephropathy (dNP) or
vascular nephropathy (vNP). The aim of the study was to determine differences in
the progression of renal insufficiency and the prevalence of vascular diseases in
the two patient groups. METHODS: In a retrospective study, we investigated type 2
diabetic patients with chronic renal insufficiency who were undergoing regular
controls in our outpatient care unit for at least 3 years prior to the start of
dialysis. We evaluated only patients who had already died under chronic dialysis
therapy, and whose diagnosis of primary renal disease was histologically
conformed at autopsy. A total of 40 type 2 diabetic patients were included in the
study. Of these, 28 patients had dNP (age 62 +/- 8 years) and 12 had vNP (age 70
+/- 7 years). The following parameters were determined at 3- to 6-month
intervals: body weight, BP, HbA1c, serum creatinine (Cr), Cr clearance (Cockroft
formula), cholesterol and triglycerides. The prevalence of vascular disease in
the two groups was also assessed. RESULTS: The average decrease in Cr clearance
was 7.7 +/- 2.4 ml/min/year in patients with dNP and 7.7 +/- 2.1 ml/min/year in
those with vNP (NS). During the entire observation period, mean HbA1c values (7.0
+/- 0.8 vs. 6.8 +/- 0.6%), systolic BP (137 +/- 8 vs. 138 +/- 11 mm Hg) and
diastolic BP (86 +/- 4 vs. 87 +/- 7 mm Hg), cholesterol and triglycerides did not
differ significantly in the two groups. The prevalence of vascular disease 3
years prior to and at the start of dialysis therapy was similar in patients with
dNP and vNP. CONCLUSION: The progression of dNP and vNP is similar at least
during 3 years before the start of dialysis therapy. Vascular risk factors and
the prevalence of vascular diseases were not significantly different in the two
patient groups. However, diabetic patients with ESRD secondary to dNP were
significantly younger than those with vNP.
PMID- 17035712
TI - Is 44-hour better than 24-hour ambulatory blood pressure monitoring in
hemodialysis?
AB - The aim of this study is to evaluate if hemodialysis (HD) patients with similar
blood pressure (BP) in the whole inter-HD period could have different target
organ lesions and survival if the behavior of BP differs from the first to the
second day of the inter-HD period. The present study compares 44-hour ambulatory
BP monitoring (ABPM) patterns in 45 HD patients. Three BP patterns emerged: group
A (n = 15) had similar BPs throughout (138 +/- 11/88 +/- 12 in the first 22 h vs.
140 +/- 11/87 +/- 12 mm Hg in the second 22-hour period); group B (n = 15) had a
significant systolic BP rise from the first to the second period (132 +/- 15/80
+/- 12 vs. 147 +/- 12/86 +/- 13 mm Hg, p < 0.05); group C (n = 15) had
significantly higher BPs (p < 0.05) than the other 2 groups throughout the whole
inter-HD period, with no significant change between the 2 halves (172 +/- 14/108
+/- 12 vs. 173 +/- 18/109 +/- 14 mm Hg). Ventricular mass and survival during the
30-month follow-up period were statistically significantly better in group A,
intermediate in group B and worse in group C. The data suggest that a 44-hour
ABPM is more accurate than a 24-hour one in evaluating organ lesion and prognosis
in HD patients.
PMID- 17035713
TI - Chloroacetaldehyde as a sulfhydryl reagent: the role of critical thiol groups in
ifosfamide nephropathy.
AB - Chloroacetaldehyde (CAA) is a metabolite of the alkylating agent ifosfamide (IFO)
and putatively responsible for renal damage following anti-tumor therapy with
IFO. Depletion of sulfhydryl (SH) groups has been reported from cell culture,
animal and clinical studies. In this work the effect of CAA on human proximal
tubule cells in primary culture (hRPTEC) was investigated. Toxicity of CAA was
determined by protein content, cell number, LDH release, trypan blue exclusion
assay and caspase-3 activity. Free thiols were measured by the method of Ellman.
CAA reduced hRPTEC cell number and protein, induced a loss in free intracellular
thiols and an increase in necrosis markers. CAA but not acrolein inhibited the
cysteine proteases caspase-3, caspase-8 and cathepsin B. Caspase activation by
cisplatin was inhibited by CAA. In cells stained with fluorescent dyes targeting
lysosomes, CAA induced an increase in lysosomal size and lysosomal leakage. The
effects of CAA on cysteine protease activities and thiols could be reproduced in
cell lysate. Acidification, which slowed the reaction of CAA with thiol donors,
could also attenuate effects of CAA on necrosis markers, thiol depletion and
cysteine protease inhibition in living cells. Thus, CAA directly reacts with
cellular protein and non-protein thiols, mediating its toxicity on hRPTEC. This
effect can be reduced by acidification. Therefore, urinary acidification could be
an option to prevent IFO nephropathy in patients.
PMID- 17035715
TI - Tutorial in biostatistics: Analyzing associations between total plasma
homocysteine and B vitamins using optimal categorization and segmented
regression.
AB - Data analysts consider standard regression models (e.g., generalized linear
model) or nonparametric smoothing techniques (e.g., loess or splines) when
examining the association between two variables. Before this step, a quantile
based summarization is typically used for exploring the exposure-response
relationship. Unfortunately, these exploratory approaches may not be optimal or
efficient for guiding the formal analysis in many biological and nutritional data
settings. We suggest a recently developed method for selection of cutpoints as a
tool of data summary and segmented regression as a modeling approach in the
analysis of plasma total homocysteine and related vitamins. These methods are
often complementary in discovering the underlying complex pattern of association.
PMID- 17035714
TI - Socio-demographic variation of dementia subtypes in china: Methodology and
results of a prevalence study in Beijing, Chengdu, Shanghai, and Xian.
AB - OBJECTIVE: To characterize sociodemographic variations in the prevalence of AD
and VaD in China. METHODS: Data were collected in a 1997-1998, cross-sectional,
door-to-door prevalence survey of 34,807 community residents ages > or =55 years
in Beijing, Shanghai, Chengdu and Xian. Initial diagnoses of AD and VaD were
assessed by clinicians using standardized protocols, according to the NINCDS
ADRDA and NINDS-AIREN criteria; diagnoses were confirmed after 6 months by
repeating neuropsychological evaluations. Prevalence odds ratios were estimated
in logistic models adjusting for survey design, age, and other sociodemographic
factors. RESULTS: We identified 732 prevalent cases of AD and 295 cases of VaD.
Adjusting for all sociodemographic factors concurrently, prevalence odds of AD
and VaD were higher in northern versus southern China. Age trends for AD appeared
different in western and eastern China. AD also showed an age-adjusted elevation
among women and, in the fully adjusted model, a gender education interaction
indicating a female preponderance in the highest education group. North-south
variation for VaD was age-dependent. In the fully adjusted model, for AD, widowed
had significantly higher prevalence odds; for VaD, widowed persons and minorities
had significantly lower prevalence odds; professionals had statistically
significant and borderline lower prevalence odds for both VaD and AD; sales
service occupations had significantly lower odds for AD only. CONCLUSION: We
observed variations in prevalence for AD and VaD in different regions and
demographic groups in China that persisted after controlling for potential
confounding factors. Sociodemographic factors are probable surrogates for
conditions such as lifestyle, environment, comorbidities, and life expectancy.
PMID- 17035716
TI - Induction of apoptosis in HaCaT cells by photodynamic therapy with chlorin e6 or
pheophorbide a.
AB - The two photosensitizers, chlorin e6 and pheophorbide a, were tested in an in
vitro model of topical photodynamic therapy (PDT). Both dyes accumulate in HaCaT
keratinocytes as verified by fluorescence measurement but pheophorbide a is
enriched fivefold more strongly than chlorin e6 after 24 h. HaCaT cells are
susceptible to PDT with both dyes. The phototoxicity measured by ATP
bioluminescence is caused by necrosis and apoptosis depending on the
photosensitizer used and the treatment modality. Chlorin e6 shows higher toxic
potential because it elicits nearly 90% cell mortality 24 h after PDT comparable
to pheophorbide a but with a fivefold lower rate of accumulation. These results
implicate caution with topical PDT of oncologic diseases due to the risk of
serious side effects on healthy skin in the course of topical photodynamic
treatment. But the lack of dark toxicity and the time-dependent enrichment of
both dyes in HaCaT cells are arguments for the application of these sensitizers
in topical PDT of non-malign skin disorders. Further studies are necessary to
discover appropriate lower doses and mechanisms of action of topical PDT with
both compounds.
PMID- 17035717
TI - In vitro percutaneous absorption and in vivo stratum corneum distribution of an
organic and a mineral sunscreen.
AB - Sunscreens, whose main function is to protect the skin against the harmful
effects of solar irradiation, should remain at the skin surface or impregnate the
first layers of the stratum corneum only and not penetrate into the underlying
living tissue. The goal of this work was to assess the penetration of titanium
dioxide (TiO(2)) and methylene bis-benzotriazoyl tetramethylbutylphenol (MBBT),
included in a broad-spectrum sunscreen formulation, into human skin in vivo,
using the tape stripping method, and in vitro, using a compartmental approach. An
additional objective was to propose an easy and minimally invasive approach to
determining the percutaneous uptake of sunscreens following topical application.
TiO(2) and MBBT were quantified using colorimetric assay and HPLC analysis,
respectively. The transmission electron microscopy and particle-induced X-ray
emission techniques were used to localize the TiO(2) in skin sections. More than
90% of both sunscreens was recovered in the first 15 tape strippings. In addition
we have shown that the remaining 10% did not penetrate the viable tissue, but was
localized in the furrows and in the opened infundibulum. Less than 0.1% of MBBT
was detected in the receptor medium, and no TiO(2) was detected in the follicle,
viable epidermis or dermis. Thus, this in vivo and in vitro penetration study
showed an absence of TiO(2) penetration into the viable skin layers through
either transcorneal or transfollicular pathways and negligible transcutaneous
absorption of MBBT. However, differences in distribution within the stratum
corneum reinforced the need for a complementary approach, using minimally
invasive in vivo methodology and in vitro compartmental analysis. This
combination represents a well-adapted method for testing the safety of topically
applied sunscreen formulations in real-life conditions.
PMID- 17035718
TI - Improvement of epidermal barrier properties in cultured skin substitutes after
grafting onto athymic mice.
AB - Barrier function in cultured skin substitutes (CSS) prepared from human cell
sources was measured by noninvasive (surface hydration, transepidermal water
loss) and invasive methods (water permeation, niacinamide flux) before and after
grafting onto athymic mice. In vitro measurements were made on days 7 and 14.
Although three of the four measures of barrier function improved markedly from
day 7 to 14, the values obtained were still far from those obtained with native
human skin controls. Additional CSS were grafted onto athymic mice on day 14, and
skin was harvested 2 and 6 weeks after grafting. Grafting brought about a
substantial decrease in all measurements by 2 weeks and almost complete
normalization of barrier function after 6 weeks. The most sensitive measure of
this recovery was niacinamide permeability, which decreased from (280 +/- 40) x
10(-4) cm/h in vitro to (17 +/- 30) x 10(-4) cm/h 2 weeks after grafting and (5
+/- 2) x 10(-4) cm/h 6 weeks after grafting, versus control values of (2 +/- 2) x
10(-4) cm/h in human cadaver skin and (0.6 +/- 0.4) x 10(-4) cm/h in human
epidermal membrane prepared from freshly excised breast skin. These results
demonstrate the reformation of epidermal barrier function after transplantation
and provide insights for the development of a functional epidermal barrier in CSS
in vitro.
PMID- 17035719
TI - Real-timereflectance confocal microscopy, a noninvasive tool for in vivo
quantitative evaluation of comedolysis in the rhino mouse model.
AB - BACKGROUND: Near-infrared reflectance confocal microscopy (RCM) is a noninvasive
tool that provides real-time images of thin virtual horizontal tissue sections.
AIMS/METHODS: We have used a rhino mouse model in combination with topical
application of all-trans-retinoic acid and all-trans-retinol to investigate the
usefulness of RCM as a noninvasive imaging tool to evaluate comedolysis in vivo
and over time. Optical images were correlated with routine histology. RESULTS:
Our results demonstrate that RCM in vivo can visualize the process of
transformation of utriculi (pseudocomedones) towards a normal-appearing
follicular structure during retinoid treatment. The retinoic acid intervention
group showed a dose-related response, while the vehicle-treated group did not
show utricular changes. CONCLUSIONS: RCM represents a useful tool for in vivo
morphological and quantitative evaluation of skin utriculi over time and could be
used as an adjunct tool to histopathological techniques for comedolysis studies.
PMID- 17035720
TI - In search for new antipsoriatic agents: NAD topical composition.
AB - The aim of the study was to examine the effectiveness of the oxidized form of
nicotinamide adenine dinucleotide (NAD(+)), adenosine precursor, in 37 patients
suffering from psoriasis. As NAD(+) is known to be relatively unstable, the
second goal was to establish the proper conditions for the satisfactory stability
of topical NAD(+) composition. In each patient, two matching plaques were
selected for the study. Topical treatment with 1 or 0.3% NAD(+) in Vaseline
ointment administered twice daily was compared with overnight therapy with 0.1%
anthralin applied for 12 h and placebo. The enzymatic method was applied to
determine the stability of NAD(+) in Vaseline ointment. After a 4-week
application, the reduction in erythema, infiltration and desquamation caused by 1
or 0.3% topical NAD(+) composition was similar to the reduction caused by 0.1%
anthralin. It was demonstrated that NAD(+) underwent a considerable decomposition
at room temperature, while it was sufficiently stable at 5 degrees C; thus, for a
longer use the agent should be stored at fridge temperature. NAD(+) therapy
combines good efficacy, cosmetic acceptability and convenient twice-daily
application.
PMID- 17035721
TI - Anti-inflammatory and skin-hydrating properties of a dietary supplement and
topical formulations containing oligomeric proanthocyanidins.
AB - BACKGROUND: Anti-inflammatory and skin hydration properties of a dietary
supplement and 2 topical formulations (Anthogenol) with oligomeric
proanthocyanidins were investigated. METHODS: Forty-two subjects were randomized
into 2 groups: one taking the dietary supplement (100 mg/day) and the other
without supplement. After 4 weeks, erythema was induced using UV radiation
followed by treatment with topical cream or lotion. Erythema was measured for up
to 72 h after irradiation. Skin hydration after 1 and 2 weeks of application of
the cream and lotion was also measured in separate test fields. RESULTS: Both
topical formulations led to a significant suppression of erythema formation and
the dietary supplement led to an additional slightly stronger suppression. Thus
72 h after UV exposure and compared to the control fields of patients that had
not taken a dietary supplement, erythema was slightly (13.2%) lower in the
subjects that had taken a dietary supplement. The cream resulted in a maximal
reduction of erythema of 45.9% (p = 0.0015), while the lotion resulted in a
maximal reduction of 53.1% (p = 0.0002). Both topical formulations also increased
skin hydration (by nearly 20%; p < 0.002 for all combinations of dietary
supplementation and topical treatment) and the hydration was higher in the group
taking the dietary supplement. CONCLUSION: The regular use of Anthogenol products
may help to protect from free-radical-mediated skin inflammation and to increase
skin hydration.
PMID- 17035722
TI - Topical bioavailability of triamcinolone acetonide: effect of occlusion.
AB - BACKGROUND/AIMS: Occlusion by covering the skin with an impermeable wrap enhances
skin hydration, affects drug absorption and can induce the formation of a drug
reservoir within the stratum corneum. This is desired in local therapy with
topical corticosteroids. The aim of the study was to investigate the effect of
occlusion before (experiment 1) and after (experiment 2) application on the
penetration of triamcinolone acetonide (TACA) into the stratum corneum. METHODS:
The experiments were conducted on the forearms of 10 healthy volunteers. In
experiment 1, 100 microg/cm(2) TACA in acetone were applied on 3 sites per arm,
one arm having been pre-occluded for 16 h. In experiment 2, the same dose was
applied on 2 sites per arm, and one arm was occluded after application until skin
sampling. Stratum corneum samples were removed by tape stripping at 0.5, 4 and 24
h (experiment 1) and 4 and 24 h (experiment 2) after application. Corneocytes and
TACA were quantified by ultraviolet-visible spectroscopy and HPLC, respectively.
The total TACA amount penetrated into the stratum corneum was evaluated by
multifactor ANOVA. RESULTS: TACA penetration into the stratum corneum with and
without pre-occlusion (experiment 1) showed no significant difference and
decreased with time. Occlusion after application (experiment 2) produced a marked
TACA accumulation within the stratum corneum, which persisted for 24 h.
CONCLUSION: Pre-occlusion showed no effect on the topical bioavailability of TACA
in the stratum corneum. In contrast, post-occlusion enhanced the TACA penetration
by a factor of 2, favouring the development of a drug reservoir.
PMID- 17035723
TI - Influence of applied quantity of sunscreen products on the sun protection factor-
a multicenter study organized by the DGK Task Force Sun Protection.
AB - It is often debated that the protection against solar-induced erythema under real
conditions is dependent upon the amount of sunscreen applied. It is believed that
when too little is applied a lower sun protection than indicated on the label
will result. The aim of this study was to quantify this effect. In this
multicenter study, the influence of three different amounts (0.5, 1.0, 2.0
mg/cm(2)) of three commercial sunscreen products in three reliable test centers
was investigated according to the test protocol of The International Sun
Protection Factor Test Method. The main result was a linear dependence of the SPF
on the quantity applied. Taking into consideration the volunteer-specific
variations, an exponential dependence of confidence interval of the in vivo SPF
and amount applied was found. The highest amount applied (2.0 mg/cm(2)) was
linked to the lowest confidence intervals. Thus, from the point of view of
producing reliable and reproducible in vivo results under laboratory conditions,
the recommendation of this multicenter study is an application quantity of 2.0
mg/cm(2).
PMID- 17035725
TI - Phytic acid: a phytochemical with complementary and alternative benefits.
PMID- 17035724
TI - The roles of autophagy in cerebral ischemia.
AB - Recent studies indicate the existence of autophagy in cerebral ischemia, but the
functions of autophagy in this setting remain unclear. Here we discuss the role
of autophagy in cerebral ischemia based on our own publication and the literature
on this subject. We propose that oxidative and endoplasmic reticulum (ER)
stresses n cerebral ischemia-hypoxia are potent stimuli of autophagy in neurons.
We also reviewed evidence suggesting autophagosomes may have a shorter half-life
in neurons and that a fraction of LC3 protein is degraded within autolysosomes,
leading to a smaller detectable amount of LC3-II in the brain while there are
clear indications of on-going autophagy. Finally, we suggest autophagy is an
important modifier of cell death and survival, interacting with necrosis and
apoptosis in determining the outcomes and final morphology of deceased neurons.
PMID- 17035726
TI - Thymidylate synthase as a chemotherapeutic drug target: where are we after fifty
years?
PMID- 17035727
TI - The problem of platinum resistance.
PMID- 17035728
TI - Delivering papillomavirus vaccines when and where they are most needed.
PMID- 17035729
TI - Enhancing the efficacy of photodynamic therapy by a chinese herbal medicine for
hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) ranks the sixth among the most common
malignancies, with chronic HBV infection being the most common cause. HCC is more
common in Africa, China and south-east Asia, but its incidence in the USA, Canada
and Australia is rising. Current treatment modalities for HCC are not effective,
and only a small percentage of patients are suitable for surgical resection and
liver transplantation. Thus other treatment options and improvement of available
modalities are badly in need. Photodynamic therapy (PDT) may have some
therapeutic benefit for patients with HCC. The study by Tang et al. has
implicated that coupled with Pheophorbide a (Pa), PDT may offer therapeutic
benefit for patients with HCC. Inhibition of cell proliferation and induction of
apoptosis by Pa may be mechanistically responsible for Pa-PDT. As Pa is an
extract from a Chinese herbal medicine Scutellaria Barbata, which is widely
available, less toxic and less expensive, such a combination may find a better
clinical usage in the treatment of HCC patients. More studies are mandatory to
fully elucidate the efficacy and mechanisms of Pa-mediated PDT.
PMID- 17035730
TI - Safety and immunogenicity of a combination measles, mumps, rubella and varicella
vaccine (ProQuad).
AB - BACKGROUND: A combination measles, mumps, rubella, and varicella vaccine
(ProQuad, Merck & Co., Inc, West Point, PA) was evaluated in five clinical
trials. Use of ProQuad would result in fewer injections for children and would
facilitate universal immunization against all four diseases. OBJECTIVE: To
describe the combined results obtained from the studies conducted during the
clinical development program for ProQuad. METHODS: A total of 5833 healthy
children, 12-23 months of age, and 399 healthy children, 4-6 years of age,
received 1 or 2 doses of ProQuad in five controlled clinical trials. M-M-R II and
VARIVAX were used as the control for most studies. Safety was evaluated for six
weeks postvaccination and immunogenicity was assessed six weeks after each dose
by a sensitive assay (ELISA or gpELISA). RESULTS: A single dose of ProQuad in 12-
to 23-month-old children was shown to be as immunogenic as a single dose of M-M-R
II and VARIVAX and was generally well tolerated. ProQuad can be used
concomitantly with other vaccines (hepatitis B and Hoemophilus influenzoe b). A
higher rate of fever was reported after 1 dose of ProQuad compared to M-M-R II
and VARIVAX, but fever episodes were transient without long-term sequelae. Both a
2-dose regimen of ProQuad in 12- to 23-month-olds and use of ProQuad in place of
M-M-R II at 4-6 years were shown to be immunogenic and well tolerated. The
incidence of adverse experiences following a second dose of ProQuad was lower
than that following the initial dose. CONCLUSIONS: A single dose of ProQuad is as
immunogenic as M-M-R II and VARIVAX and is well tolerated in a 1- or 2-dose
schedule. ProQuad should easily fit into the routine immunization schedule.
PMID- 17035731
TI - Preclinical evaluation of a chimeric malaria vaccine candidate in Montanide ISA
720: immunogenicity and safety in rhesus macaques.
AB - Several malarial antigens are in development as potential vaccine candidates as
part of a concerted effort to control the disease, which kills more than one
million people per year. Although some antigens have demonstrated an impact
against the malaria parasite, Plasmodium falciparum, many researchers hypothesize
that a combination of antigens will be required to generate high levels of
efficacy against clinical disease. PfCP2.9 is a chimeric protein that includes
MSP119 and domain III of AMA1 [AMA1 (111)] of Plasmodium falciparum in a single
recombinant molecule. The antigen, formulated in Seppic's ISA 720 adjuvant, is
approaching Phase I clinical testing in humans. The purpose of this study was to
assess the safety of this vaccine and to explore possible dosage levels for
clinical evaluation. Groups of five monkeys each were immunized i.m. with 25
microg, 50 microg, 100 microg and 200 microg of PfCP2.9/ISA 720 in 0.5 mL on days
0 and 112. The mean anti-PfCP2.9 titres to the 50 microg dose group were higher
than the other dose groups; however, there was no statistically significant
difference between the anti-CP2.9 titres of any of the groups, suggesting that
the immune response to PfCP2.9 was saturated at 25 microg. One animal in the 100
microg dose group elicited a higher antibody and IFN-gamma response to PfCP2.9
than the rest of the cohort; this animal developed a small sterile abscess
following the second vaccination, which spontaneously resolved within one week.
IN CONCLUSION: (a) 50 microg is highly immunogenic, appears safe, and is likely
to be an appropriate dose for clinical evaluation; and (b) a conservative trial
design is warranted to avoid any unexpected reactogenicity with the PfCP2.9/ISA
720 formulation.
PMID- 17035732
TI - Is autophagy the key mechanism by which the sphingolipid rheostat controls the
cell fate decision?
AB - Sphingolipids are major constituents of biological membrane and some of them
behave as second messengers involved in the cell fate decision. Ceramide and
sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide
promotes cell death and S1P increases cell survival. We have shown that both
sphingolipids are able to trigger autophagy with opposing outcomes on cell
survival. Here we discuss and speculate on the diverging functions of the
autophagic pathways induced by ceramide and S1P, respectively.
PMID- 17035733
TI - Long term responses with cetuximab therapy in glioblastoma multiforme.
PMID- 17035734
TI - Comparison of saftey and immunogenicity of purified chick embryo cell rabies
vaccine (PCECV) and purified vero cell rabies vaccine (PVRV) using the Thai Red
Cross intradermal regimen at a dose of 0.1 ML.
AB - Intradermal (ID) vaccination with modern cell culture rabies vaccines is a means
to significantly reduce the cost of post-exposure prophylaxis as compared to
intramuscular vaccination. In this study we evaluated the efficacy,
immunogenicity and tolerability of PCECV and PVRV administered ID in doses of 0.1
mL per site according to the 2-site Thai Red Cross (TRC) regimen. Patients with
WHO category III exposure to suspect or laboratory proven rabid animals were
administered either PCECV (n = 58) or PVRV (n = 52) ID at a dose of 0.1 mL per
site at two sites on days 0, 3 and 7 and at one site on days 30 and 90. Serum
samples were withdrawn on days 0, 14, 30, 90 and 180 and rabies virus
neutralizing antibody (RVNA) titers were determined by rapid fluorescent focus
inhibition test (RFFIT). Patients who were exposed to laboratory confirmed rabid
animals were followed up for one year after exposure. All 110 patients developed
RVNA titers above 0.5 IU/mL by day 14. Adequate titers >0.5 IU/mL were maintained
up to day 180. Both vaccines induced equivalent RVNA titers at all time points
and were well tolerated. Five subjects who were bitten by laboratory confirmed
rabid dogs were alive and healthy one year after exposure. As demonstrated, PCECV
and PVRV are both immunogenic, efficacious and well tolerated when administered
in the TRC post-exposure prophylaxis regimen in ID doses of 0.1 mL as recommended
by WHO guidelines. The use of PCECV in this regimen may prove more economical in
developing countries like India.
PMID- 17035735
TI - Fever as a marker of reactogenicity of an acellular pertussis-containing
hexavalent vaccine (HEXAVAC) in a large-scale, open, randomized safety study in
healthy French infants.
AB - OBJECTIVE: New multivalent vaccines simplify childhood immunisation schedules and
can increase vaccination coverage. However, they must have a reactogenicity
profile which is acceptable and comparable with that of previously available
vaccines. The objective of this trial was to assess the incidence of fever of
40.0 degrees C or higher following vaccination with HEXAVAC or concomitant
PENTACOQ and HBVAXPRO. STUDY DESIGN: This was an open, randomized, pragmatic,
post-licensure multicenter trial performed in France. Infants were randomly
assigned to receive either a single injection of a hexavalent, aP-containing
vaccine (HEXAVAC) or separate injections of a pentavalent, wP-containing vaccine
(PENTACOQ) and Hepatitis B vaccine (HBVAXPRO) at 2, 3 and 4 months of age. Both
groups received a HEXAVAC booster at 12-18 months of age. RESULTS AND DISCUSSION:
7151 infants were enrolled in 389 centers. During the combined three-day periods
following the primary series injections, the incidence of fever of 40.0 degrees C
or higher with HEXAVAC was not greater than with [PENTACOQ and HBVAXPRO]. The
incidence of fever at thresholds of 38.0 degrees C, 38.5 degrees C, 39.0 degrees
C and 39.5 degrees C was significantly lower in the HEXAVAC group. The vaccine
attributable risk for fever of 40.0 degrees C following the booster injection
with HEXAVAC was statistically acceptable. CONCLUSION: The incidence of fever of
40.0 degrees C or higher in this study was very low and similar in both groups
(HEXAVAC or [PENTACOQ + HBVAXPRO] as a three-dose primary series). Fever > or
=38.0 degrees C and < or =39.5 degrees C was significantly less frequent
following administration of HEXAVAC. The incidence of fever of 40.0 degrees C or
higher following a HEXAVAC booster dose was low in all infants studied.
PMID- 17035736
TI - Activation of beta-catenin signaling pathways by classical G-protein-coupled
receptors: mechanisms and consequences in cycling and non-cycling cells.
AB - Wnt signaling pathways are some of the most intensely studies in all of biology.
Recently, a number of classical heterotrimeric G protein coupled receptors
(GPCRs) have been shown to activate the canonical Wnt pathway, culminating in the
stabilization of beta-catenin and induction of transcription of genes regulated
by the Tcf/Lef family of transactivators. However, mechanisms by which these
GPCRs accomplish this differ in key ways, and in some circumstances, the
phenotypes produced are novel. Herein, we will examine mechanisms by which
classical GPCRs interact with the canonical Wnt pathway, culminating in its
activation, and describe the consequences of this activation, focusing on the
heart. In the heart, the contractile cells, or cardiomyocytes, are terminally
differentiated and virtually exclusively grow by increasing cell size
(hypertrophy) rather than cell number, and we will describe how GPCR-mediated
activation of the canonical pathway can drive this process.
PMID- 17035738
TI - The politicization of antimicrobial resistance.
PMID- 17035737
TI - A fluorescent peptide substrate for measuring the ADP-ribosylation activity of
the cholera toxin A-subunit.
AB - Vibrio cholerae serogroups O1 and O139 Bengal produce cholera toxin (CT) a
typical AB5 bacterial toxin comprising an ADP-ribosylation enzyme A-subunit (CTA)
and a carbohydrate binding B-subunit (CTB). DUKORALR the inactivated oral cholera
vaccine has recently been licensed for use in the European Union. This vaccine
contains killed whole cells of V cholerae and 1 mg of purified recombinant CTB
(rCTB). DUKORALR has a good safety profile and there has been no indication that
active CT is present. Nevertheless, an assay that confirms the absence of active
CTA in the vaccine is advantageous to ensure vaccine safety. Conventional assays
such as the Y-cell assay cannot detect biologically active amounts of CT in
DUKORALR because of the large amount of rCTB present. We have developed an assay
based on a fluorescently labelled 11-mer peptide substrate that detects CTA
activity despite the presence of excess rCTB.
PMID- 17035739
TI - Glycopeptide resistance in staphylococci.
AB - Glycopeptide antibiotics have become the last bastion for the treatment of
multidrug-resistant Gram-positive hospital pathogens, the two main ones being
methicillin-resistant S. aureus and enterococci. However, in addition to the
emergence of vancomycin resistance in enterococci, certain staphylococcal strains
with low-level resistance to glycopeptides have increasingly been isolated from
clinical specimens. This review focuses on mechanisms of resistance,
epidemiology, control measures and therapeutic options for these staphylococci.
PMID- 17035740
TI - Treatment of otitis media.
AB - Otitis media is a very common reason for the prescription of antibiotics in
children. Antimicrobial therapy is mostly empirical, based on the knowledge of
the frequency and susceptibility patterns of causative pathogens and of the
penetration and other pharmacokinetic properties of several oral antibiotics.
Pharmacoeconomic considerations must also be taken into account.
PMID- 17035741
TI - New antimicrobial agents for Gram-positive infections.
AB - Increasing antimicrobial resistance in Gram-positive bacteria has presented a
formidable treatment problem. The enterococci, although traditionally non
virulent pathogens, have been shown, when associated with vancomycin resistance,
to have an attributable mortality of approximately 40%. The frightening specter
of widespread vancomycin resistance in the more virulent Staphylococcus aureus
would have a significantly greater impact. Since the late 1980s, advances have
been made in the development of pharmacological weapons against multiply
resistant Gram-positive bacterial infections. At least seven new antimicrobial
classes that have activity against resistant Gram-positive organisms are in
various stages of development. Most are semisynthetic derivatives of known
antibiotics; however, importantly, a unique class of antimicrobial agent has also
emerged.
PMID- 17035742
TI - Pharmacokinetic and pharmacodynamic modelling of antibiotic therapy.
AB - Despite the advances in pharmacokinetic and pharmacodynamic modelling, there is
still much more to gain from this concept. The use of pharmacokinetic and
pharmacodynamic modelling in vitro, in animal and in human models has confirmed
that an index, such as peak concentration divided by the minimum inhibitory
concentration (Cmax/MIC), the area under the curve divided by the minimum
inhibitory concentration (AUC/MIC) and time above the minimum inhibitory
concentration (T>MIC), may be used as an aid to understanding better the
variability between patients who receive similar antibiotic dosage regimens but
have dissimilar outcomes. Efforts to find the optimal pharmacokinetic or
pharmacodynamic index predictive of response is crucial to identify targets that
will ensure efficacy and for the prediction of failure.
PMID- 17035743
TI - Immunological effects of macrolides.
AB - Various reviews have highlighted the potential immuno-modulating properties of
macrolides. Recent data in this field raise the possibility of new therapeutic
prospects in cancer and inflammatory diseases (cystic fibrosis, asthma,
atherosclerosis, etc.). Advances have also been made in our understanding of the
interactions between macrolides and host immune effectors, particularly
phagocytes. The third millennium should see exciting new uses of macrolides.
PMID- 17035745
TI - Chemotherapy of malaria.
AB - Clinical trials continue to provide evidence for the efficacy of semi-synthetic
artemisinin derivatives and the novel fixed dose combination therapies Malarone,
co-artemether and chlorproguanil-dapsone. Single agents under development include
the 8-aminoquinoline etaquine, pyronaridine and azithromycin. Preclinical
interest in synthetic endoperoxides and quinoline analogues remains high and a
significant is also being made in natural product chemistry. Dihydrofolate
reductase remains a molecular drug target of interest, whereas phospholipid
metabolism represents a new approach. Genomic information is likely to produce
many new drug targets for exploration in the coming decade.
PMID- 17035746
TI - Chemotherapy of leishmaniasis: recent advances in the treatment of visceral
disease.
AB - New lipid formulations of amphotericin B--AmBisome, Amphotec, and Abelcet--have
dramatically decreased the toxicity associated with amphotericin B and have made
this group of agents the treatment of choice for visceral leishmaniasis. An agent
of a completely different chemical class, the aminoglycoside aminosidine, was 97%
curative in India. This agent too may be used for visceral leishmaniasis.
PMID- 17035747
TI - Changing patterns of disease and treatment of opportunistic parasitic infections
in patients with AIDS.
AB - In the past 18 months, the significant effect of highly active antiretroviral
therapy and immune reconstitution on the incidence of opportunistic protozoan
infections, mainly cryptosporidiosis and microsporidiosis, has been demonstrated
in HIV-infected patients. The major therapeutic advances of the past 18 months
concern microsporidiosis, for which the efficacies of fumagillin and albendazole
have been assessed against Enterocytozoon bieneusi and Encephalitozoon
infections, respectively. The efficacy of macrolides is still uncertain for the
treatment of cryptosporidiosis; however, promising results were obtained with
nitazoxanide. The incidence of toxoplasmosis has markedly decreased as a result
of the efficacy of specific prophylaxis, and visceral leishmaniasis is still
considered as an emerging opportunistic disease during AIDS.
PMID- 17035749
TI - New therapies for the treatment of chronic hepatitis B infection.
AB - Persistent hepatitis B virus infection can lead to the development of chronic
liver disease, cirrhosis and primary hepatocellular carcinoma. The only therapy
of confirmed benefit in chronic hepatitis B is interferon alpha, which can lead
to long-term benefit in only a third of highly selected patients. A number of new
therapeutic approaches are being actively developed for treating chronic
hepatitis B, including the use of nucleoside analogues, cytokines, antisense
oligonucleotides, ribozymes, dominant negative mutants and DNA-based vaccines.
Recent clinical trials with the nucleoside analogues have identified several
important challenges for future drug development, in which the gene therapy-based
approach may prove useful either alone or most probably in various combinations.
Future clinical trials should aim to address these challenges using the new
therapies so that the goal of substantial and sustained inhibition of viral
replication with the accompanying improvement in the underlying liver disease can
be achieved.
PMID- 17035750
TI - In-vitro and in-vivo efficacy of influenza neuraminidase inhibitors.
AB - Influenza continues to be a major health concern and there is always the threat
of a pandemic due to the emergence of a viral strain new to the human population,
as exemplified by the avian influenza A/H5N1 virus which was responsible for six
deaths in Hong Kong last year. Data reported in the past year, based on in-vitro,
in-vivo (animal) and clinical studies, suggest that a new class of antiviral
compounds targeting the viral neuraminidase is likely to be useful for the
treatment and prevention of influenza virus infections in humans.
PMID- 17035751
TI - Specific therapies for human papilloma virus infections.
AB - Human papillomavirus induces the hyperproliferation of epithelial cells, leading
to a broad spectrum of human diseases, ranging from benign warts to malignant
neoplasms, depending on the location of the lesion, the immune status of the
patient and the type of human papillomavirus. Current therapies for human
papillomavirus-associated diseases are based on the excision or ablation of
dysplastic or malignant tissue, and are associated with a high frequency of
recurrent disease, discomfort and costs. A better understanding of the viral
replicative cycle and of the interaction between the virus and the host cell,
particularly the cell cycle regulation, has opened new perspectives. Recently,
new treatment modalities for human papillomavirus-induced lesions have been
identified, including the use of antiviral/immunomodulatory therapies, such as
cidofovir, antisense oligonucleotides, imiquimod and human papillomavirus
vaccines.
PMID- 17035752
TI - Treatment guidelines and clinical realities.
PMID- 17035753
TI - Latent reservoirs for HIV-1.
AB - Combination therapy for HIV-1 infection can reduce viremia to undetectable
levels, suggesting that prolonged treatment might eradicate the infection.
However, one potential mechanism for viral persistence involves the establishment
of a state of latent infection. Recent studies have directly confirmed that HIV-1
establishes a state of latent infection in resting memory CD4(+) T cells in vivo.
This reservoir is likely to frustrate current efforts to eradicate the infection
with combination therapy.
PMID- 17035754
TI - Metabolic abnormalities and body fat redistribution in HIV-1 infected patients:
the lipodystrophy syndrome.
AB - A unique and unexpected syndrome consisting of metabolic abnormalities
(hyperlipidaemia and insulin resistance) and body fat redistribution (central
adiposity and peripheral fat wasting) has been reported with increasing frequency
in HIV-1 infected patients, most of whom are receiving highly active
antiretroviral therapies including HIV-1 protease inhibitors. This article
reviews the clinical and laboratory characteristics, the pathogenesis, and the
management of this syndrome.
PMID- 17035755
TI - Mother to infant transmission of HIV.
AB - Mother-to-infant transmission is the route by which the vast majority of children
acquire HIV. Several refinements in our understanding in how to reduce the risk
of transmission have been made in the past year. The risks from prolonged breast
feeding, and the protective effects of caesarean section have been clarified.
Shorter interventions using antiretroviral drugs are useful in resource
constrained settings. In developed countries, combination antiretroviral
therapies to reduce maternal viral loads to below limits of detection are being
explored, but there is concern about toxicity particularly of indinavir in
pregnancy. Combining interventions can reduce transmission rates to less than 2%.
PMID- 17035756
TI - HIV drug resistance tests are here to stay.
AB - The clinical indications for HIV drug resistance testing are discussed. The major
limitations of using resistance testing in the clinical setting are the lack of
evidence for a clinical benefit, the costs and the amount of knowledge required
for a good interpretation of the results. In those situations in which these
limitations can be overcome or are considered less important, resistance testing
may be used today. For widespread clinical use, however, trials creating large
databases and the design of expert systems translating the results for the use in
individual patients will be required.
PMID- 17035758
TI - Importance of drug resistance in gonococci: from mechanisms to monitoring.
AB - Neisseria gonorrhoeae isolates continue to develop an impressive arsenal of
resistance mechanisms to antimicrobial agents, including resistance to some of
the antibiotics presently recommended for the treatment of gonococcal infections.
PMID- 17035759
TI - Which test is best for chlamydia?
AB - Nucleic acid amplification tests are now the tests of choice for diagnosing
Chlamydia trachomatis infection. For the first time there are diagnostic tests
for Chlamydia trachomatis that are more sensitive than tissue culture. Another
major advantage is that they can be used with first-catch urine specimens and
vaginal swabs. It is thus possible to test for genital chlamydial infection
without using invasive specimen collection methods.
PMID- 17035760
TI - In pursuit of a human chlamydial vaccine.
AB - The best way to control chlamydial diseases is with an effective vaccine.
Although previous studies suggest that a vaccine is an achievable goal, progress
has been limited even though many vaccination strategies have been tested. A
clearer understanding of the immunobiological basis of chlamydial protection and
pathology will be critical for future research in chlamydial vaccination.
PMID- 17035761
TI - Bacterial vaginosis: sequelae and management.
AB - The prevalence and complications of bacterial vaginosis are population dependent.
In pregnancy, bacterial vaginosis is associated with late miscarriages and
infection driven pre-term delivery. Regardless of the aetiology of pre-term
delivery, surviving infants are at increased risk of subsequent
neurodevelopmental handicap. Intervention studies in bacterial vaginosis positive
pregnant women at high risk of pre-term delivery demonstrate the benefits of
antibiotic treatment. Current evidence suggests that bacterial vaginosis may
increase the efficiency of heterosexual HIV transmission. Metronidazole remains
the mainstay of treatment of bacterial vaginosis. No treatment prevents relapse,
which occurs in 20-30% of cases within 1 month. New approaches that are based on
a better understanding of the pathophysiology of bacterial vaginosis are required
to improve the clinical management of recurrent bacterial vaginosis.
PMID- 17035762
TI - Novel strategies for treating candidiasis.
AB - In this review the recent achievements in the field of chemotherapy and
immunotherapy of candidiasis are outlined. The current limitations of
chemotherapeutic approaches and the lack of well defined preventive tools and
strategies make it imperative to exploit the potential of novel immunotherapeutic
venues. In this prospect the rather extensive work performed on cytokine patterns
in experimental models and the upsurge of antibodies as one mechanism of anti
Candida protection raises great promise for the clinical use of immunotherapy
possibly in conjunction with chemotherapy to improve the fight against this
increasingly prevalent human opportunistic infection.
PMID- 17035763
TI - Interactions between human papillomavirus and other sexually transmitted agents
in the etiology of cervical cancer.
AB - The interplay between human papillomavirus, notably type 16, and HIV in cervical
carcinogenesis leads to persistent infection and cervical neoplasia by
destruction of the afferent arm (Langerhans cells) of the host immune system. The
joint effect takes place at the early stages of squamous intraepithelial lesions
and has severe consequences if left untreated. The recent increase of cervical
cancer mortality in young women in developed countries may well be a result of
the HIV epidemic. Infection with Chlamydia trachomatis is associated with
cervical squamous cell carcinoma but not with cervical adenocarcinoma, and the
association remains after adjusting for human papillomavirus 16. Joint effects of
C. trachomatis and the human papillomaviruses have not been studied at the
population level but indirect evidence from epidemiological studies suggests that
the interaction might be different (synergistic versus antagonistic) at different
stages (cervical intraepithelial neoplasia versus invasive cervical cancer) of
cervical carcino-genesis. Concomitant exposure to human papillomaviruses 6 or 11
and human papillomavirus type 16 has not been shown to result in excess risk of
cervical squamous cell carcinoma. This antagonistic joint effect was also
discovered between human papillomavirus types 18 and 16, as well as 33 and 16.
Herpes simplex virus type 2 antibodies are associated with a modest risk of
cervical cancer, which is not surprising since the presence of herpes simplex
virus antibodies reflects risk-taking sexual behaviour. However, no excess risk
remains after adjustment for human papillomavirus type 16, and no interaction
between these two viruses has been found in epidemiological studies. Evidence of
interaction between human papillomavirus type 16 and the other members of the
herpesvirus family is still at an experimental level and difficult to judge.
Little progress has been made in the most promising experimental association
between the oncogenic human papillomaviruses and adeno-associated viruses. In
addition to the well established interaction between human papillomaviruses and
HIV, intriguing interactions are emerging between the human papillomaviruses and
C. trachomatis, as well as between the different human papillomavirus types.
PMID- 17035764
TI - Current world literature.
PMID- 17035765
TI - Acute bronchitis: an indication for antibiotic avoidance.
PMID- 17035766
TI - Laboratory diagnosis of respiratory infections.
AB - The laboratory diagnosis of infections of the respiratory tract is not an exact
science, with many clinicians electing to empirically select antimicrobial
therapy without the benefit of laboratory testing. With trained laboratory
personnel and the proper selection of tests, accurate laboratory diagnosis is
available. Progress is occurring most rapidly with molecular methods, such as
polymerase chain reaction (PCR) testing. As molecular approaches are technically
simplified and become less expensive, advances in the laboratory diagnosis of
most respiratory tract infections caused by fastidious pathogens will occur. The
diagnosis of non-fastidious bacteria, that require in-vitro antimicrobial
testing, will continue to require conventional culture methods. New bronchoscopic
methods, quantitative evaluation of cultures, and recognition of intracellular
bacteria in stained smears do improve the usefulness of conventional culture and
stain in the diagnosis of pneumonia.
PMID- 17035767
TI - The other causes of 'atypical' pneumonia.
AB - Mycoplasma, Chlamydia and Legionella are the usual organisms considered to be the
etiologic agents of 'atypical' pneumonia. Other microorganisms such as bacteria,
viruses, parasites, fungi and mycobacteria can also present with atypical
pneumonia manifestations. Outbreaks and isolated cases of respiratory viruses
with atypical pneumonia presentations have been reported among immunocompetent
and immunosuppressed patients. Severe infections due to these respiratory viruses
alone or as a concomitant bacterial or viral infection have been observed.
Additionally, in endemic areas, certain zoonotic infections may present as
atypical pneumonia.
PMID- 17035768
TI - Update of Legionella infections.
AB - Legionella spp. are significant causes of both community-acquired pneumonia and
nosocomial pneumonia. More than 40 species of Legionella have now been
identified. The spectrum of disease ranges from asymptomatic infection to serious
disease, with two specific syndromes identified: Legionnaire's disease and
Pontiac fever. Hospital-acquired infection arises from the presence of Legionella
in the hospital water supply. The optimal approach for the detection and
prevention of nosocomial infection is debatable-whether or not periodic sampling
of hospital water systems should be carried out in the absence of clinical cases
is controversial. Newer macrolides or newer fluoroquinolone agents are the
preferred therapy for serious diseases caused by Legionella.
PMID- 17035769
TI - Management decisions regarding community-acquired pneumonia.
AB - The successful management of community-acquired pneumonia requires many
management decisions, including a decision as to the site of care, the type and
duration of antibiotic therapy, and a discharge decision for patients who require
hospitalization. A number of recent studies have defined and tested criteria for
some of the management decisions indicated above.
PMID- 17035770
TI - Advances in antimicrobial therapy of community-acquired pneumonia.
AB - Community-acquired pneumonia has a significant impact upon healthcare in North
America and worldwide. In the U.S. it is responsible for three to four million
cases yearly and 78,000 deaths. It is not a homogeneous entity and it may be
caused by a number of pathogens including Streptococcus pneumoniae, the atypicals
(Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella species) Haemophilus
influenzae and Gram-negative rods. While it is clear that directed therapy is the
ideal, empiric therapy is likely to remain the norm for some time to come. This
is because of limitations in current diagnostic techniques, the possibility of
infection with co-pathogens and the broad spectrum of antimicrobial activity
required to treat the various pathogens which may be responsible for infection in
any given patient. Of great concern is the increase in the incidence of resistant
pathogens seen in community-acquired pneumonia. Of particular significance are
the isolates of S. pneumoniae which display resistance to penicillin and
macrolides although the exact clinical relevance has yet to be determined. New
guidelines for the treatment of community-acquired pneumonia have been developed
by the Infectious Disease Society of America which include the new
fluoroquinolones. These agents offer the potential for monotherapy of community
acquired pneumonia in cases which previously required combination regimens such
as a macrolide and a beta-lactam. There is great concern however, that these
agents not be used inappropriately thereby hastening the emergence of resistance
to the fluoroquinolone class of antimicrobials.
PMID- 17035772
TI - Current world literature.
PMID- 17035771
TI - Vaccines to prevent respiratory infection: opportunities on the near and far
horizon.
AB - Illnesses caused by respiratory pathogens result in great loss of life, suffering
and commitment of resources for treatment. That the suffering and loss of life
can be prevented through immunization has already been clearly shown with
existing vaccines, such as those for Haemophilus influenzae type b, Streptococcus
pneumoniae, and influenza. The emergence of drug-resistant pathogens is making
reliance on therapy more expensive and perhaps less successful, accentuating the
need to focus on prevention. Although several effective vaccines to prevent
respiratory infections currently exist, they are underutilized globally.
Improvements in immunogenicity, efficacy, and ease of administration, and
lowering the costs of some of the existing vaccines would augment the potential
for prevention worldwide. The greatest opportunities for the prevention of
respiratory infections will rest with vaccines that will become available in the
future.
PMID- 17035773
TI - Microbial antigens, heat shock proteins and skin disease.
PMID- 17035774
TI - Heat shock proteins and skin diseases.
AB - Heat shock proteins are chaperones to construct protein molecules and are widely
distributed in prokaryotic and eukaryotic cells. They are also induced by
environmental stress to protect cells. Human heat shock proteins cross-react with
bacterial heat shock proteins to modulate immune responses to induce
autoimmunity. They are involved in the differentiation and growth of neoplastic
cells as well as normal cells. They are also involved in various inflammatory
skin diseases and in fibrotic process. Heat shock proteins play important roles
in the pathogenesis of many skin diseases.
PMID- 17035775
TI - Biology and epidemiology of scabies.
AB - Only recently have attempts been made to develop techniques for the early
identification of scabies infections and to identify the genome of the mites.
Most work with scabies employs rudimentary technology and requires skill for
accurate diagnosis. Many countries still have no widely available dermatology
service to deal with this infection and its sequelae.
PMID- 17035776
TI - Mycobacterium marinum infections.
AB - Mycobacterium marinum is a saprophytic mycobacteria capable of causing soft
tissue infection in humans, usually acquired by inoculation. As with other
mycobacterial infections, diagnosis may be difficult and recent developments in
molecular biology are also being applied to atypical mycobacteria such as
Mycobacterium marinum.
PMID- 17035777
TI - Molluscum contagiosum: new perspectives on an old virus.
AB - Renewed interest in molluscum contagiosum virus has been stimulated by the
availability of the entire genomic sequence and the identification of more than
160 putative genes, some of whose functions are now under analysis. Important
findings have been generated by the recognition that certain viral proteins have
anti-chemotactic and anti-apoptotic properties. Other advances include the
characterization of two recombinant immunoreactive proteins, and the publication
of the first seroepidemiological survey of the general population. Recent
clinical studies indicate that some of the newer antiviral agents and physical
treatment modalities offer significant benefits for the treatment of recalcitrant
infections in the immunosuppressed.
PMID- 17035779
TI - Immunomodulation for the treatment and prevention of bacterial infections: a
challenge for the next millennium.
PMID- 17035778
TI - The immunology of Propionibacterium acnes and acne.
AB - The majority of recent publications on the immunology of Propionibacterium acnes
relate to the potential use of the bacterium as an adjuvant or its use in rodent
models of human inflammatory disease. These studies have increased the
understanding of the potential effects of Propionibacterium acnes on cells of the
mononuclear phagocyte system. Research into the immunology of acne and the role
that Propionibacterium acnes plays in inflammatory acne has been limited, with
efforts being focussed on the problems of Propionibacterium acnes resistance to
antibiotics. Recent studies have indicated that inflammatory acne is a T cell
mediated disease, but whether Propionibacterium acnes is the initial stimulus for
either the specific or non-specific recruitment of T cells in acne lesions is
still a matter for conjecture.
PMID- 17035780
TI - Infective endocarditis: new concepts in pathogenesis.
AB - Gram-positive cocci account for the large majority of cases of infective
endocarditis. Pathogenesis investigations of endocarditis have therefore focused
on purported virulence factors in staphylococci, viridans group streptococci and
enterococci. In addition to novel molecular techniques that have been adapted for
use in the examination of gram-positive cocci, animal models of experimental
endocarditis have been employed to support or discount the role of specific
bacterial components in production of infective endocarditis. This review details
recent work that addresses endocarditis pathogenesis and highlights pertinent
findings from these investigations.
PMID- 17035781
TI - Otitis media today: a challenge for physicians and the community.
AB - Acute otitis media is one of the most common causes of medical consultation
worldwide, and has a high economic impact. In this review, a clear definition
between acute otitis media and otitis media with effusion is presented. The
microbiology and characterization of the main bacterial isolates in acute otitis
media and the susceptibility patterns are reviewed, and the latest concepts in
antimicrobial treatment are discussed. The need for courses that improve the
capability of primary care physicians to diagnose acute otitis media using
pneumatic otoscopy, and for parental education is also discussed.
PMID- 17035782
TI - Superantigens and autoimmune disease: are they involved?
AB - In over 10 years since the definition of superantigens, much has been learned
about host cell-superantigen interactions. The initial simple set of rules used
to define these interactions has given way to a more complex system, in which the
activation of multiple cell types can occur as a consequence of superantigen-cell
interactions or as a result of bystander effects based on the induction of a
specific cytokine milieu. As a consequence, our ideas concerning the ways in
which superantigens might be involved in disease are also expanding rapidly. This
review highlights some of the many different pathways of superantigen-associated
pathogenesis currently under investigation.
PMID- 17035783
TI - Host responses to secreted Shigella virulence factors.
AB - Shigella and related enteropathogens deliver effector molecules into the
cytoplasm of epithelial cells and macrophages via a type III secretion system.
Epithelial cells respond to contact with Shigella by rearranging the
cytoskeleton, which leads to uptake of the bacterium. Apart from several
cytoskeletal proteins, this process involves the recruitment and activation of
kinases, and the small GTPase rho. Macrophages infected with Shigella undergo
apoptosis and release mature IL-1beta, a pro-inflammatory cytokine. This
apoptotic pathway requires caspase-1 (IL-1beta-converting enzyme). Pro
inflammatory macrophage apoptosis triggers acute shigellosis and might be
relevant in other infectious diseases.
PMID- 17035784
TI - Chlamydia trachomatis: the role of cellular and humoral immune mechanisms in the
development of blindness.
AB - Ocular infection with Chlamydia trachomatis leading to trachoma is the commonest
cause of treatable blindness worldwide. Although effectively controlled by
improved sanitation, a chlamydial vaccine may prove a more cost-effective method
of protection against this disease in the medium term. The development of
vaccines against Chlamydia trachomatis has been hampered by a lack of
understanding of the immune responses leading to protection or pathology,
particularly in humans. Although a strong cell-mediated immune response (T helper
lymphocyte type 1) is almost certainly necessary to resolve intracellular
chlamydial infection, a humoral (T helper lymphocyte type 2) response may protect
against colonization and limit immunopathological events. Recent studies
addressing this potential conflict are reviewed.
PMID- 17035785
TI - Reactivation of herpes simplex virus: the role of cytokines and intracellular
factors.
AB - Considerable progress has been achieved in relating environmental stimuli and
viral genetics to herpes simplex virus reactivation. The cytokines IL-1, IL-6,
nerve growth factor NGF, and interferons have been implicated in herpes simplex
virus reactivation. These molecules may act as signals which convey important
information about the environment to the latent viral genome. Herpes simplex
virus latency associated transcript expression is important for viral
reactivation. The function of these unique viral RNA's is not completely
understood, but they appear to be necessary for the efficient establishment of a
latent infection in the ganglion. A better understanding of the mechanisms
underlying the herpes simplex virus reactivation can be expected to lead to novel
effective treatments for herpes simplex diseases.
PMID- 17035786
TI - Association between the biological characteristics of HIV-1, vertical
transmission of infection and clinical progression of pediatric disease.
AB - The design of effective prophylactic measures to prevent the vertical
transmission of HIV-1 and of therapies to alter the natural progression of
pediatric HIV disease requires a thorough understanding of basic pathogenetic
principles. Maternal viral load, the biological behavior of HIV, such as
replicative capacity in different types of cells, monocyte/macrophage tropism,
and the capacity of the infant's cells to support infection have all been
assessed for their contribution to the risk of mother-to-child transmission.
Similarly, the effects of viral load and phenotype (e.g. replicative capacity,
cell tropism, syncytium-inducing capacity and the use of chemokine co-receptors)
have all been investigated as parameters associated with variations in the
expression of clinical disease in children. Some of the extant data are
conflicting, but general principles regarding pathogenesis are beginning to
emerge.
PMID- 17035787
TI - Hepatitis C in children.
AB - Mother-to-child, or vertical transmission, of hepatitis C virus is now the
dominant mode of acquisition of infection for children. The rate of transmission
is low in women who are not also HIV-positive. Whether the mode of delivery is
associated with transmission remains questionable; breast-feeding does not appear
to be a source of infection. The detection of hepatitis C virus RNA using the
polymerase chain reaction is a sensitive method for the early diagnosis of
infection in perinatally exposed infants, but false positive results can occur.
The natural history of hepatitis C virus infection in children is not well
defined, but chronic infection is common in most cases. The disease progression
is slower than in adults. Therapeutic trials (not placebo controlled) in a small
number of children suggested a sustained response to interferon treatment in only
a minority of cases. The option of combination therapy with ribavirin looks
promising and needs evaluation.
PMID- 17035788
TI - The epidemiology and pathogenesis of infections caused by the high numbered human
herpesviruses in children: HHV-6, HHV-7 and HHV-8.
AB - Human herpesvirus 6 may be transmitted from saliva to infants, but other routes
of transmission, such as organ and bone marrow transplantation, have also been
reported. Intrauterine infection has also been suggested. Although the clinical
symptoms during the primary infection in children are mild, human herpesvirus 6
may have neurotropic properties and be involved in the pathogenesis of febrile
seizures in infants. The clinical symptoms caused by human herpesvirus 7 are not
yet clear, but reports have described neurological symptoms. Human herpesvirus 8
has been identified from Kaposi's sarcoma tissue using molecular procedures.
Serological study shows that human herpesvirus 8 is not so common in society and
the mode of transmission is still unclear. Several routes of infection have,
however, been considered, including sexual transmission.
PMID- 17035789
TI - Rational treatment of pulmonary infections in patients with cystic fibrosis.
AB - The life expectancy of patients with cystic fibrosis has increased markedly
during the past two decades due in large part to improved clinical care,
including the use of more effective antimicrobial agents for Pseudomonas.
However, the chronic lung disease of CF remains the principal cause of mortality.
A growing understanding of the complex interactions between infection and
inflammation has led to new approaches for treatment, including chronic use of
aerosolized antibiotics, particularly tobramycin, in patients known to be
colonized/infected with P. aeruginosa and anti-inflammatory treatments to slow
the progression of lung disease.
PMID- 17035790
TI - Natural history and long-term consequences of Lyme disease in children.
AB - Lyme disease is the most common vector-borne infection affecting children living
in temperate parts of the western hemisphere. The widespread anxiety about the
long-term consequences of the illness, however, finds no support in the
literature. Although the number of long-term follow-up studies is limited, the
prognosis in children treated for Lyme disease seems to be extremely favourable.
PMID- 17035791
TI - Current world literature.
PMID- 17035792
TI - Antibiotic resistance-systems thinking, chaos and complexity theory.
PMID- 17035793
TI - Surveillance of antibiotic resistance.
AB - Resistance among bacteria is on the rise, both in the hospital and in the
community. Surveillance is needed for guided empiric treatment and to detect new
resistance mechanisms at an early stage. Surveillance shows a wide variation in
resistance among hospitals and countries. Especially methicillin-resistant
Staphylococcus aureus and vancomycin-resistant enterococci are uncommon in north
western European countries but frequently observed otherwise elsewhere. Among
Gram-negative bacteria regional differences are less obvious. Many hospitals all
over the world suffer from recurrent outbreaks by Enterobacteriaceae that produce
extended spectrum beta-lactamases, Acinetobacter, etc. Because of the evolving
pattern of resistance, surveillance should be done at regular intervals in all
hospitals and in the community.
PMID- 17035794
TI - Lessons from recent nosocomial epidemics.
AB - This review describes important examples of recent nosocomial infection
epidemics. Current trends suggest that emerging problems in nosocomial infections
include increased nosocomial epidemics in out-of-hospital settings, contamination
of medical devices and products, and antimicrobial resistance. Increased
attention should be focused on outbreak investigations in these areas.
PMID- 17035795
TI - Nosocomial pneumonia.
AB - Nosocomial pneumonia remains an important infection that warrants continuing
investigation. The past year has seen a number of reports further describing risk
factors, controversial issues around diagnosis, and potential preventive
strategies. For specific infecting organisms such as Legionnaire's disease and
tuberculosis, further reports of issues related to water supply in the former and
staff preventive programs in the latter have also been reported. Substantive
advances in prevention or management have not, however, been identified.
PMID- 17035796
TI - Nosocomial diarrhoea.
AB - Toroviruses have been reported as a new cause of nosocomial viral diarrhoea, and
the role of astroviruses has been further elucidated. Polymerase chain reaction
methods promise to improve the diagnosis and understanding of the aetiology and
control of hospital-acquired viral gastroenteritis. A clearer picture of the
impact and extent of Clostridium difficile diarrhoea has emerged, and several
control measures have been described. An epidemic Clostridium difficile strain
and toxin A-deficient strains have been reported. There is growing evidence that
enterotoxin-producing Clostridium perfringens can also cause antibiotic
associated diarrhoea.
PMID- 17035797
TI - Orthopaedic implant infections.
AB - Recent advances have defined risk factors for orthopaedic implant infections that
suggest modifications in the clinical care of certain patients. For diagnosis,
new work shows the importance of obtaining multiple specimens for culture, and
the enlarging spectrum of causative organisms. The potential for the polymerase
chain reaction is demonstrated. In treatment, the value of rifampicin is shown in
controlled and open trials.
PMID- 17035798
TI - Pathogen 'shift' in febrile neutropenia.
PMID- 17035799
TI - Infection in the neutropenic and stem cell transplant patient.
AB - The spectrum of infectious complications in neutropenic patients after stem cell
or bone marrow transplant is not very different from that seen in other
neutropenic patients, with the possible exception of fungal infections. The
prevention and therapy of these infections remain a major challenge. The
management of neutropenic patients after stem cell or bone marrow transplant has
markedly benefited from the development of new antiviral agents and the use of
granulocyte/macrophage colony stimulating factors.
PMID- 17035800
TI - New anti-cancer therapies, new opportunities for infection.
AB - Therapeutic approaches in the practice of haematology/oncology are increasing in
complexity. Agents such as the purine analogues and monoclonal antibodies may
introduce a new spectrum of infection as a consequence of prolonged/profound
lymphoid suppression. The use of high dose therapy with stem cells support is
increasing rapidly in clinical practice. Allogeneic transplantation is associated
with prolonged immunosuppression and a high potential for transplant-related
mortality from infection. This has led to intense interest in strategies aimed at
improved prophylaxis and treatment of infective complications. This review aims
to summarize recent advances in haematological practice and the effect this has
had on opportunistic infections.
PMID- 17035801
TI - Infections in solid organ transplant recipients.
AB - A disturbing trend in evolution for sometime has culminated in the fact that
resistant Gram-positive bacteria including enterococci and staphylococci have
emerged as the leading pathogens at many transplant centers. Recently published
reports have highlighted the formidable challenge such antimicrobial-resistant
microorganisms now pose in transplant recipients. Studies published within the
past year have documented the clinical relevance of human herpesvirus-6 after
transplantation, as well as the transmission of human herpesvirus-8 by
transplanted allograft and the subsequent development of Kaposi's sarcoma in
these patients. A novel hepatitis virus has been discovered; studies to elucidate
its significance in the transplant setting are underway.
PMID- 17035802
TI - Pneumocystis carinii infection in non-AIDS patients.
AB - Infection with the opportunist fungus Pneumocystis carinii remains a significant
cause of morbidity and mortality in non-HIV-infected individuals immunosuppressed
by a wide range of malignancies, transplantation and inflammatory conditions.
Glucocorticoid use appears to be an independent risk factor for the development
of Pneumocystis carinii pneumonia. Transmission from infected to susceptible
patients may occur, albeit infrequently. A diagnosis of Pneumocystis carinii
pneumonia may be achieved in the majority of cases by DNA detection using
polymerase chain reaction on oropharyngeal mouth washes.
PMID- 17035803
TI - Unusual infections and novel therapy in the immunocompromised host.
AB - Many of the reports of infection in immunocompromised patients over the past year
have been caused by unusual bacterial pathogens or fungi, which are often
multiresistant and difficult to treat. Although many difficulties still remain
some progress has been made over the past year in the development of new
antimicrobial agents and alternative therapies.
PMID- 17035804
TI - Bibliography. Current world literature. Nosocomial and hospital-related
infections.
PMID- 17035805
TI - The virtues of epidemiology.
PMID- 17035806
TI - Recent developments in mycobacterial research.
AB - Tuberculosis remains a major health problem in the world, which is compounded
further by the alarmingly high rate of M. tuberculosis infections in AIDS
patients. Thus, there is an urgent need to advance our understanding of the
mycobacterium to develop new drugs. The extraordinary recent developments in
mycobacterial genetic research, particularly in genomics will greatly facilitate
this goal. The knowledge of the entire genome sequence of M. tuberculosis will
help in designing new chemotherapeutic and immunotherapeutic interventions. This
review highlights recent developments in genomics, mycobacterial genetics, novel
vaccine strategies, and our understanding of tuberculous dormancy.
PMID- 17035807
TI - Dengue vector surveillance and control.
AB - This review describes efforts being undertaken to develop new tools and
strategies to monitor and control dengue fever mosquitoes, mainly Aedes aegypti.
With the growing realization that the magnitude of the global dengue/dengue
haemorrhagic fever problem rivals that of malaria and infectious diseases such as
hepatitis, and that old strategies are unsuitable in today's world, this problem
requires urgent attention. The new tactics involve proper targeting of important
breeding sites and diverse control methodologies ranging from biological control
to molecular transformation of the vectors themselves.
PMID- 17035808
TI - Travel medicine.
AB - This review covers significant recent developments in the field of travel
medicine. New vaccines related to travel are discussed: cholera, Lyme disease,
and rotavirus. Pertinent travel vaccine-related issues with varicella, polio,
meningitis, Japanese encephalitis, and tick-borne encephalitis are described. New
developments in malaria prophylaxis, diagnosis and treatment are discussed.
Imported cases of African tick bite fever, arboviruses, African trypanosomiasis,
and Helicobacter pylori, and diarrheal illness are reviewed.
PMID- 17035810
TI - Gastrointestinal infections: rapid advances in knowledge.
PMID- 17035809
TI - Gulf War Syndrome: potential role of infectious diseases.
AB - Following the 1991 war with Iraq, some US, British, and Canadian veterans began
experiencing diverse symptoms, which have been characterized as a possible 'Gulf
War Syndrome'. Although veterans have been found to have a variety of illnesses,
neither the existence nor etiology of a unique syndrome has been confirmed. In
this review of current literature, the potential for infectious diseases to cause
health problems nearly a decade after the Gulf War is evaluated.
PMID- 17035811
TI - Viral gastroenteritis.
AB - A large number of viruses can be found in the human intestine. Some
(bacteriophages) infect the bacteria present as normal flora and others use the
gut as a portal of entry. This review examines the virology, pathogenesis,
immunology, epidemiology, clinical features, treatment and prevention of the
viral enteropathogens. Rotavirus is undoubtedly the most important, causing an
estimated 800,000 deaths each year, especially in developing countries. Recently,
an oral live quadrivalent rhesus rotavirus vaccine has been licensed for use in
the USA. It has great potential but there are a number of hurdles to be overcome
before it can be given to infants in developing countries. Molecular techniques
are revolutionizing our understanding of rotavirus pathogenesis, and the
tremendous diversity of Caliciviridae and Astroviridae, as well as producing new
diagnostic techniques and vaccines.
PMID- 17035812
TI - Bacterial gut infections.
AB - Infections of the bowel as a result of bacterial enteropathogens are one of the
most common medical problems. The use of novel molecular biology techniques and
the recent development of new antimicrobial drugs and vaccines are helping us to
identify, understand, treat and prevent these infections.
PMID- 17035813
TI - Parasitic infections of the intestines.
AB - Intestinal parasites remain extremely common worldwide. In developing countries,
intestinal protozoans are important causes of childhood diarrhea.
Cryptosporidiosis is a common cause of chronic diarrhea in patients with AIDS.
With the advent of current active antiretroviral therapy the incidence of
cryptosporidiosis in AIDS has decreased. By contrast, Cryptosporidium,
Cyclospora, and Giardia outbreaks continue to be associated with contamination of
food or water. The intestinal helminths Ascaris, hookworm, and Trichuris each
infects over a thousand million people. While most of those infected experience
only minor symptoms, recent data highlight subtle effects of parasitism on
cognitive function and nutrition. Efforts at disease control in developing
countries are increasingly focused on mass chemotherapy.
PMID- 17035814
TI - Human microsporidial infection and possible animal sources.
AB - Sources of human microsporidial infection remain speculative, but possible animal
reservoirs are emerging. Of the common human microsporidial infections,
Enterocytozoon bieneusi has now been identified in non-human primates, pigs, dogs
and a cat; Encephalitozoon intestinalis in dogs, pigs, cows, goats and donkeys
and Encephalitozoon hellem in budgerigars and parrots. Evidence of species
heterogeneity is also emerging suggesting that some animal isolates may be
distinctive. Further molecular epidemiological studies need to be undertaken to
clarify which animal genotypes can also infect humans. Some of the less common
microsporidial infections found in humans, such as those involving Pleistophora
like species, may be the result of infrequent accidental exposure (for example,
inadequately cooked infected fish muscle) and establishment, particularly if the
individual is severely immunocompromised.
PMID- 17035816
TI - Bibliography. Current world literature. Tropical and travel-associated diseases.
PMID- 17035815
TI - Viral hepatitis.
AB - Hepatitis A is still the most frequently reported vaccine preventable disease. A
reduction in the incidence will only be achieved by routine childhood vaccination
rather than by targeted vaccination of high-risk groups. A larger vaccine program
is warranted. Hepatitis B remains a large public health problem. Vaccination
targeted to high-risk adults failed to decrease the incidence of hepatitis B
virus (HBV) infection. Sexual as well as nosocomial transmission remain serious
problems. Vaccine escape variants have also been identified in newborns from
infected mothers who had been vaccinated at birth. Clearance of HBV infection
results from complex immune mechanisms including TH1 cytokines significantly
associated with HLA class II alleles. Escape HBV mutants, especially precore
mutants, influence the outcome. The sequences of the promoter and other critical
regions were associated with severe activity. Lamivudine is a major advance in
therapy of chronic hepatitis B which was recently approved in many countries.
Although drug resistant mutants may be selected during therapy, additional
nucleoside analogues including adefovir are promising. Optimal combination
strategies of different active compounds need to be researched. Three per cent of
the world population has been infected with hepatitis C virus (HCV). Epidemiology
has shifted from transfusion to non-transfusion settings. Intravenous drug abuse
is currently the main risk but nosocomial infection is also of concern. Three
independent factors seem associated with fibrosis progression: age, daily alcohol
consumption of 50 g or more and male gender. Median duration of progression to
cirrhosis is about 30 years. At the cirrhotic stage, about 3-5% of patients per
year develop hepatocellular carcinoma. There is little evidence that direct
cytopathicity plays a significant role in liver cell injury. HCV also infects
extrahepatic cells which seems critical in the pathogenesis of the many
extrahepatic manifestations. The recent identification of CD81 protein as one of
the HCV receptor candidates may help us to understand how chronic HCV infection
may trigger a wide spectrum of clinical manifestations, autoimmune or even
lymphoproliferative, through potent continuous B cell activation in the context
of various host and/or environmental cofactors. Direct measurement of HCV RNA has
clarified HCV replication kinetics and variability. Among patients with chronic
hepatitis C, 48 weeks of treatment with interferon/ribavirin therapy produced a
response rate of 28% among those with genotype 1 and 66% with other genotypes.
Similar differences were found for combination therapy among patients who had
relapsed following previous interferon (IFN) therapy. Viral load prior to
treatment has been clearly shown to be predictive of response to interferon
treatment, with increased viral load associated with decrease rates of response.
In patients non-responsive to interferon, a second course of interferon alone has
no beneficial effect whereas combination therapy may induce response in 25%. In
conclusion, combination therapy should be given in all situations. Viral
eradication should not be the only objective of the treatment since histological
improvement may be obtained despite persisting viral replication with prolonged
maintenance of antiviral therapy.
PMID- 17035817
TI - Antibiotic efflux mechanisms.
AB - Bacterial genomes sequenced to date almost invariably contain genes apparently
coding for multidrug efflux pumps, and the yeast genome contains more than 30
putative multidrug efflux genes. Thus it is not surprising that multidrug efflux
is a major cause of intrinsic drug resistance in many microorganisms, and plays
an even more prominent role in organisms with a low-permeability cell wall, such
as Gram negative bacteria in general and Pseudomonas aeruginosa in particular, as
well as Mycobacterium species. Furthermore, overproduction of intrinsic pumps, or
acquisition of pump genes from external sources, often results in high levels of
resistance. This review discusses the classification of efflux proteins, their
mechanism of action, the regulation of their expression, and the clinical
significance of efflux pumps.
PMID- 17035818
TI - The epidemiology of vancomycin-resistant enterococci.
AB - Major differences in the epidemiology of vanA carrying enterococci exist between
Europe and the USA, where these organisms have been well investigated. These
differences are probably related to the differences in antibiotic use in humans
and animals in both continents, but more research is needed before firm
conclusions can be drawn.
PMID- 17035819
TI - The role of quinolones in chronic obstructive pulmonary disease.
AB - Chronic obstructive pulmonary disease is a disease state characterized by the
presence of airflow obstruction due to chronic bronchitis and/or emphysema. The
airflow obstruction is generally progressive. In the past asthma was often
confused with chronic obstructive pulmonary disease but as the cellular
inflammatory mechanisms are quite different to chronic bronchitis and emphysema
it is prudent to separate this condition of airway hyper-responsiveness.
Exacerbation of chronic obstructive pulmonary disease is a considerable burden on
health service resources in terms of morbidity and mortality. Approximately one
half of exacerbations can be attributed to bacterial pathogens, the major
pathogens being Haemophilus influenzae, Streptococcus pnemoniae and Moraxella
catarrhalis. Resistance to common first-line treatment antibiotics such as the
beta-lactams can be variable. Newer fluoroquinolones such as grepafloxacin,
levofloxacin, sparfloxacin, clinafloxacin, moxifloxacin, gatifloxacin and
gemifloxacin are characterized by improved activity against Gram positive
bacteria as well as their Gram negative properties. However, more randomized
controlled trials need to be accomplished before the true role of quinolones in
exacerbation of chronic obstructive pulmonary disease is clearly ascertained.
PMID- 17035820
TI - Antifungal prophylaxis in neutropenia.
AB - Despite the widespread prophylactic use of antifungal agents in neutropenic
patients, invasive fungal infections continue to emerge as major causes of
morbidity and mortality. With the exception of fluconazole prophylaxis in
allogeneic marrow transplant recipients, no firm conclusions can be drawn due to
the lack of reliable, randomized trials. At the present time, it seems that
antifungal chemoprophylaxis is more a matter of faith rather than science.
Earlier diagnosis based on noninvasive diagnostic techniques and pre-emptive
strategies may offer more promise than a liberal prophylactic approach.
PMID- 17035821
TI - Antiparasitic agents: challenges of sleeping sickness, hopes for malaria.
PMID- 17035822
TI - Recent strategies for the chemotherapy of visceral leishmaniasis.
AB - Visceral leishmaniasis is a widespread and deadly disease. First-line drugs are
antimonials, but amphotericin B and its lipid formulations B is used for treating
visceral leishmaniasis that is unresponsive to antimony. New therapeutic
approaches are being actively developed, including the following: use of drug
carriers targeted specifically to the parasite location, thus reduce adverse
effects of drug; use of immunomodulating drugs; evaluation of natural products;
pharmacokinetic studies; and drug combinations. Recent clinical trials with
paromomycin and miltefosine were successful and these drugs appear to be
promising for the future therapy of visceral leishmaniasis. Furthermore,
identification and therapeutic evaluation of specific targets in the Leishmania
organism could lead to new compounds, such as antileishmanial drugs and reversal
agents of drug resistance.
PMID- 17035823
TI - The control of the human filariases.
AB - There is a growing momentum for the global control and elimination of the major
human filariases as public health problems worldwide. The renewed optimism for
undertaking this objective reflects the development of simple and potentially
cost-effective strategies for mass drug delivery in onchocerciasis and the
availability of new extremely effective drug combinations to treat infection, and
new methods of morbidity control in lymphatic filariasis. It also reflects the
development and current availability of very effective diagnostic, surveillance
and control modeling tools for both parasites. Control programming will also be
aided by our greater understanding of the biology of transmission, host immunity
and disease pathogenesis.
PMID- 17035824
TI - New therapies and changing patterns of treatment for malaria.
AB - The launch of the Roll Back Malaria initiative by the World Health Organization
in the period under review confirms malaria's place as one of the great public
health priorities worldwide. The period 1998-1999 has seen some advances and some
disappointments in the treatment of malaria, against a backdrop of spreading drug
resistance. Most encouraging is the clear demonstration that intermittent
prospective treatment of asymptomatic pregnant women in endemic areas reduces
morbidity. The greatest disappointment has been the result of trials with the
artemether-benflumetol fixed-dose combination therapy. Questions have been raised
about several widely accepted practices, including measurement of quinine levels,
exchange transfusion, and the prophylactic use of anticonvulsants in children
with cerebral malaria.
PMID- 17035825
TI - The potential of adoptive transfer of immunity for reducing post transplant
Epstein-Barr virus-associated disease.
PMID- 17035826
TI - Antiretroviral drug level monitoring: the next routine test in HIV management?
AB - The monitoring of the pharmacokinetics of antiretroviral drugs is sometimes
thought to be the next routine test in the management of HIV. This overview will
provide some background information on the subject, and discusses whether there
is a need for therapeutic drug monitoring for antiretroviral drugs.
PMID- 17035827
TI - Bibliography. Current world literature. Antimicrobial agents: bacterial/fungal.
PMID- 17035828
TI - Prostate.
PMID- 17035830
TI - Surgery, reconstructive surgery.
PMID- 17035831
TI - Bladder, testicular neoplasm.
PMID- 17035829
TI - Imaging stone disease.
PMID- 17035833
TI - Paediatrics andrology, infertility.
PMID- 17035832
TI - Kidney, transplantation, infections.
PMID- 17035835
TI - Patient selection: the value of pressure-flow urodynamics.
AB - Considerable controversy has surrounded the evaluation of men with lower urinary
tract symptoms and benign prostatic obstruction. Various objective and subjective
evaluations have been used to aid better patient selection for treatment in order
to improve outcome. The importance of pressure-flow urodynamics has become better
appreciated in recent years, although it is plain that the urological community
is still divided regarding their use.
PMID- 17035836
TI - Holmium laser prostatectomy: a technique in evolution.
AB - This review documents the evolution of the current techniques of Holmium:yttrium
aluminium-garnet (Ho:YAG) laser prostatectomy. An increasing number of centres
are accumulating experience with this wavelength in the surgical treatment of
Benign Prostatic Hyperplasia. Newer techniques, including prostatic enucleation
combined with intracavitary morcellation, are discussed.
PMID- 17035838
TI - Phytotherapy in the treatment of benign prostatic hyperplasia.
AB - There are numerous plant extracts that have been used for the treatment of benign
prostatic hyperplasia and voiding dysfunction. While some extracts show promise,
their efficacy has not been adequately proven in long-term, double-blind, placebo
controlled trials. In addition, the mechanism of action remains poorly defined.
PMID- 17035837
TI - Minimally invasive treatment for benign prostatic hyperplasia.
AB - The armamentarium of minimally invasive treatment modalities for patients with
benign prostatic hyperplasia has constantly increased during the past decade. The
energy sources used range from micro-/radiofrequency waves to high-intensity
focused ultrasound, laser vaporization/coagulation/resection and electrosurgical
techniques. Each of these devices has its particular advantages and
disadvantages. At present, the most intensively studied techniques are
interstitial laser coagulation, holmium laser resection and new approaches to
transurethral electrosurgery.
PMID- 17035840
TI - Epidemiology of chronic prostatitis.
AB - Although there has been a recent surge of interest in chronic prostatitis, which
hopefully will translate into advances in our understanding of the distribution
and determinants of this condition, at present there is a scarcity of published
epidemiologic research on chronic prostatitis. However, from the currently
available epidemiologic studies, it appears that chronic prostatitis is common.
In addition, studies of several determinants (i.e. age, race, region, infectious
agents, uric acid, sexual activity, autoimmunity, prostate-specific antigen and
prostate biopsy) may provide clues to the etiology of chronic prostatitis.
PMID- 17035841
TI - Immunology of chronic prostatitis: etiological and therapeutic considerations.
AB - Immunological studies of prostatitis have developed from findings of antibody
coated bacteria in the 1970s to the more recent studies of various models of
autoimmunity. This review presents data suggesting that possible causes for
prostatitis (bacterial or otherwise) may be explained under an immunological
umbrella.
PMID- 17035842
TI - Cryptic bacterial infection in chronic prostatitis: diagnostic and therapeutic
implications.
AB - Chronic idiopathic prostatitis, sometimes called prostatodynia or abacterial
prostatitis, is a commonly diagnosed and poorly treated urological syndrome.
Clinically, this condition frustrates the patient and physician due to its
chronicity and resistance to therapy. Recent studies suggest that the etiology of
chronic idiopathic prostatitis may be of bacterial origin. Three types of
provocative data have demonstrated bacterial presence from prostatic specimens
(tissue and secretions) that were negative by traditional clinical microbiologic
tests: (i) presence of bacterial gene sequences in prostatic tissue encoding 16S
rRNA and tetracycline resistance (tetM-tetO-tetS); (ii) controlled cultural
findings showing coagulase-negative staphylococci as the most common isolates
(68%) in prostatodynia (chronic idiopathic prostatitis); and (iii) culture of
difficult-to-grow coryneforms in expressed prostatic secretions (EPS) on enriched
culture media and direct microscopic observation of these pleomorphic bacteria in
EPS. Additionally, earlier experimental studies in a rat model support the
concept that antibiotic therapy in chronic bacterial prostatitis may not be due
to altered antibiotic pharmacokinetics in the chronically inflamed prostate
gland. Rather, ineffective antimicrobial eradication might result from protected
bacterial micro-colonies within an infection-induced altered micro-environment
deep within the prostate gland. We postulate that extracellular slime substances
produced by bacteria that are buried in prostatic tissues could impair host
defenses by their anti-phagocytic and anti-chemotactic properties that affect
neutrophils as well as anti-proliferative characteristics that affect
lymphocytes. These extracellular slime substances could also have cytoprotective
properties which can conceal bacteria from otherwise bactericidal levels of
antibiotics and lead to recrudescent infections resistant to therapy. Persistence
of bacterial antigens might initiate a cascade of cellular immunologic events
resulting in chronic inflammation of the prostate gland.
PMID- 17035843
TI - Patient assessment in chronic prostatitis.
AB - Assessment of men suffering from proven chronic prostatitis involves a cascade of
diagnostic steps, including evaluation of symptoms and clinical features,
objectivation of the inflammatory response in expressed prostatic secretions,
standardized localization techniques for common bacteria and a search for
fastidious, uncommon pathogens.
PMID- 17035844
TI - Treatment of chronic prostatitis: an etiologicaly based approach.
AB - The therapeutics of chronic prostatitis remain as enigmatic as the disease. In
light of the recent guidelines from the National Institutes of Health, there may
finally be satisfactory evaluation of efficacy.
PMID- 17035846
TI - Imaging of renal artery stenosis.
AB - Renal artery stenosis is the cause of progressive ischemic nephropathy and of
renovascular hypertension. Due to the invasiveness of arteriography, which is
claimed to be the gold standard at the present time, several noninvasive imaging
techniques are available. Colour Doppler sonography is cost-effective, but
magnetic resonance angiography and computer tomography are more expensive;
however, both are potential candidates for the definition of a new gold standard.
Evaluation of renal vasculature by means of Doppler sonography includes intra-
and extrarenal scanning as well as power Doppler and the use of contrast agents
for enhancement of the Doppler signals. Computed tomography angiography is a
minimally invasive method for the diagnosis of renal artery stenosis. There is
high diagnostic accuracy that is not significantly different from that of
angiography with respect to main and accessory renal arteries and detection of
clinically significant renal artery stenoses. The main advantages over
angiography are the use of an intravenous approach, and direct information
provided about the vessel wall and adjacent structures. However, the
nephrotoxicity of contrast material remains a major concern. Magnetic resonance
angiography of the abdominal aorta and renal arteries has advanced considerably
over the past few years. Recently developed breath-hold three-dimensional
magnetic resonance angiography provides a new promising, noninvasive technique to
evaluate the abdominal aorta and its large branch vessels. Using this technique,
high sensitivity and specificity is achieved. The improved image quality and the
ability to detect vascular lesions is due to short acquisition time with
elimination of respiratory artifacts over an entire imaged volume by single
breath-hold acquisition. Computed tomography angiography with its fast
acquisition time and high spatial resolution compares favorably with magnetic
resonance angiography and colour Doppler sonography. However, as compared with
Doppler sonography and magnetic resonance angiography, computed tomography
angiography images display only anatomic information and lack of flow
sensitivity.
PMID- 17035847
TI - Detection of recurrent prostate cancer after cryosurgery.
AB - Cryosurgery is a new method of treating prostate cancer. Long-term results of
this treatment are not well known. Experience shows that a high percentage of
patients have detectable prostate-specific antigen within 2 years after therapy,
which raises the possibility of recurrent disease. The best method for evaluating
these patients is not yet established. Available diagnostic options are discussed
and compared.
PMID- 17035848
TI - Doppler sonography in testicular and scrotal imaging.
AB - The primary role of Doppler ultrasound of the acute testicle and scrotum is for
the diagnosis of spermatic cord torsion or epididymitis. The utility of Doppler
in other conditions such as testicular neoplasm is limited, and in general does
not increase diagnostic specificity. The application of color Doppler imaging and
power Doppler imaging increases sensitivity for the detection of orchitis and
testicular neoplasms in which the gray scale findings may be subtle. Power
Doppler imaging is more sensitive for the identification of slowly flowing blood
than color Doppler imaging. As a result, power Doppler imaging may be
particularly helpful for the diagnosis or exclusion of spermatic cord torsion as
a cause of acute scrotal pain in the prepubescent male.
PMID- 17035849
TI - Magnetic resonance imaging of urinary bladder cancer.
AB - The treatment and prognosis of urinary bladder cancer are largely determined by
the tumour stage and the presence or not of metastases. Magnetic resonance
imaging and clinical staging complement each other. Magnetic resonance imaging is
the most accurate technique for differentiating the various stages of deep tumour
infiltration and for detecting metastases, whereas clinical staging is the best
technique for differentiating between post-biopsy effects and the various stages
of superficial tumours. The role played by magnetic resonance imaging in the
staging of this disease and the monitoring of therapy is reviewed and
illustrated. Finally, the authors present an overview of the current and future
applications of this technique.
PMID- 17035850
TI - Renal magnetic resonance angiography: an update.
AB - Recent developments in renal magnetic resonance angiography have led to a
significant improvement in the technical success rate and diagnostic accuracy of
the methods. Specifically, three-dimensional contrast-enhanced magnetic resonance
angiography methods have been shown to provide a more reliable depiction of renal
artery morphology than older techniques. In addition, recent work has shown that
variations of magnetic resonance angiography methods have several important
attributes that may make it feasible to demonstrate the hemodynamic significance
of a renal artery stenosis. Recent data show that magnetic resonance angiography
methods may be used to predict patient outcome in response to revascularization
therapy.
PMID- 17035852
TI - Renal calculus disease.
AB - We have seen an explosion in technical innovations for the management of
urolithiasis. Today, the endourologist possesses an assortment of minimally
invasive tools to treat renal stones. Most patients receive fast, safe and
effective treatment in the outpatient setting. Despite the many technical
advances, however, anatomical malformations and complex stones still provide
significant challenges in diagnosis, access to a targeted stone, fragmentation,
and clearance of the resulting fragments. This review examines a variety of
urinary stone presentations and treatment strategies for cost-effective
management.
PMID- 17035853
TI - Obstructive uropathy.
AB - Recent study has increased the understanding of the physiological processes
occurring in obstructive uropathy, in particular the role played by vasoactive
mediators and cellular mechanisms. There is an emphasis on developing effective
and less invasive means of detection and treatment of ureteric obstruction,
although it remains to be determined how the techniques currently being assessed
will impact on clinical practice.
PMID- 17035854
TI - Renovascular hypertension.
AB - Renovascular hypertension is the most common cause of secondary hypertension.
Interest in identifying patients with renal artery stenosis has been stimulated
recently by advances in three areas. First, is the realization that not only can
renal artery stenosis cause renovascular hypertension, but it can also lead to
progressive renal failure (ischemic nephropathy) caused by progression of
disease, usually atherosclerotic in nature. Second, advances in percutaneous
transluminal renal angioplasty and, especially, the recent use of renal stents
has led to a less invasive management of these patients as compared with
traditional renal revascularization. Finally, the development of newer less
invasive diagnostic techniques, both for the identification of patients with
renal artery stenosis and to follow patients with known renal artery stenosis,
has simplified the diagnostic aspect of the disease.
PMID- 17035855
TI - Ischemic nephropathy.
AB - Ischemic nephropathy is an independent pathway towards end-stage renal disease.
Its prevalence is estimated to be significant and increasing among populations
with vascular disease, hypertension, and chronic renal failure. Angiography
remains the gold standard for evaluation of ischemic nephropathy; however,
selection by clinical criteria and noninvasive screening with ultrasound are
recommended for most patients. Surgical revascularization of ischemic kidneys can
halt or reverse deterioration of renal function and is preferable to medical
treatment. Direct comparison of angioplasty and stent placement with surgery is
needed.
PMID- 17035856
TI - Renal transplantation: surgical aspects, complications and results.
AB - Despite the fact that kidney transplants have routinely been successfully
performed for over 30 years there continues to be challenges for the transplant
surgeon. These include a static donor pool, growing recipient list, declining
number of ideal donors and greater reliance on marginal donors. Innovative
methods to deal with these problems continue to be sought.
PMID- 17035857
TI - The modern urologist--still a surgeon?
PMID- 17035858
TI - Peyronie's disease.
AB - The pathogenesis of Peyronie's disease is still not well understood. As a result,
the treatment of Peyronie's disease remains a dilemma and new therapies continue
to evolve. This article discusses present understanding, controversy and new
discoveries related to this condition.
PMID- 17035859
TI - Hypospadias.
AB - The incidence of hypospadias is increasing. Decreased androgen sensitivity,
5alpha-reductase deficiency and chromosomal abnormalities are causes of the
disease. Nonirritant suture material, coverage of the urethral reconstruction by
additional tissue and perioperative care positively influence the outcome.
Complication rates after repair of distal hypospadias are low. For severe
hypospadias staged procedures provide good results. Buccal mucosa is promising
for initial repair and repeat cases. Psychosocial function in patients with
severe hypospadias is normal.
PMID- 17035860
TI - Reconstructive surgery of the upper urinary tract.
AB - This paper reviews the major publications over the past year regarding upper
urinary tract reconstruction. Controversies in the diagnosis of ureteropelvic
junction obstruction and in the surgical repair of the obstructed upper urinary
tract are discussed. Special emphasis is placed on issues surrounding minimally
invasive techniques.
PMID- 17035861
TI - Urologic intestinal reservoirs: the continent outlet.
AB - General use of standardized terminology and assessment of functional
characteristics suggested by the International Continence Society will enable
better comparison of the results and technical specifications of different
continent outlets. According to the basic functional principle, continence
mechanisms can be classified into extraluminally and intraluminally located
continent outlets. Extraluminal continent outlets are easy to construct, but are
associated with the risk of overflow incontinence. The use of invagination or
intussusception nipple valves is associated with a long learning curve, tedious
surgical technique and high complication rate. There is an increasing tendency to
use the flap valve principle for construction of continent outlets, which
guarantee a high rate of complete continence with an acceptable complication
rate.
PMID- 17035863
TI - Bladder substitution: experimental data.
AB - Bladder enlargement or substitution using various segments of the
gastrointestinal tract has been associated with significant metabolic and
nutritional complications. Extensive research for other alternative materials,
both synthetic and autologous, has revealed some difficulties including
rejection, infection and stone formation. Most investigators believe that any
material used for bladder augmentation must serve as a scaffold for the
progressive ingrowth of all host bladder wall components, without infection or
rejection. Recently, acellular matrix has been successfully utilized in
experimental models for bladder substitution and appeared to satisfy many of
these prerequisites.
PMID- 17035864
TI - Tasks of surgical andrology in current interdisciplinary reproductive medicine.
AB - Although the controversy about varicocele treatment options and their benefit has
not been resolved, evidence is increasing that a cautious use of varicocele
surgery contributes to effective management of male factor subfertility.
Moreover, timely varicocele treatment might be an equally valuable prevention of
later subfertility as early treatment of cryptorchidism. In reconstructive
surgery of the ductal system, a more frequent use of tubulovasostomy can prevent
initial failure. Furthermore, the cryopreservation of spermatic fluid for
intracytoplasmic sperm injection can obviate a repeat procedure, if patency is
not reached with surgery. The surgical andrologist is also the 'retriever' of
sperm cells for assisted reproduction in cases of irreparable damage of the male
reproductive organs. Efforts to delimit critically the indications and the
results of the different techniques with large multicentre and interdisciplinary
studies should be emphasized. Finally, it is encouraging that andrology does not
rely solely on the successes and possibilities of assisted reproduction, but
continues to inquire into the causes of male subfertility (e.g. by implementing
immunohistochemical techniques into clinical research).
PMID- 17035865
TI - Surgical strategy in late-stage renal cell cancer with intracaval extension.
AB - During the past two years several reports have substantially contributed to the
surgical stratification of patients with late-stage renal cell cancer and
simultaneously occurring intracaval neoplastic extension, and our knowledge about
the clinical prognosis of the patients after nephrectomy with complete removal of
the tumour thrombosis has been extended. Recognizing the importance of a
tolerable perioperative and postoperative morbidity and mortality, it is now well
documented in the literature that a multidisciplinary approach involving the
combined use of deep hypothermia, cardiac arrest and cardiopulmonary bypass has
dramatically improved the feasibility of surgical treatment of the venous
extension above the hepatic veins. Furthermore, the diagnostic approach for
patients with intracaval thrombosis, aiming at the reliable delineation of the
cranial margin of venous extension, has been rationalized without compromising
important diagnostic information required for the surgical stratification. This
review assesses the current opinion of the surgical stratification of patients
with renal cell cancer and intracaval neoplastic extension, the most reliable and
least invasive diagnostic approach for the preoperative staging and, finally, the
independent prognostic value of neoplastic venous extension for the clinical
course of the disease.
PMID- 17035866
TI - Radical perineal prostatectomy.
AB - Radical perineal prostatectomy is viewed with increasing favor because prostate
specific antigen levels now permit exclusion of node dissection. This review
describes the surgical conduct of the procedure, and notes outcome as a function
of disease extent.
PMID- 17035867
TI - Evaluation of catheter loops in central venous port systems.
AB - OBJECTIVES: We sought to evaluate the cause for catheter loops of central venous
ports. MATERIAL AND METHODS: A total of 241 patients who received a central
venous port via subclavian vein access were included in this retrospective study.
Eighty of these patients had undergone a computed tomography of the chest,
allowing retrospective evaluation of the course of central venous catheters.
Complications were evaluated by review of the clinical data charts. RESULTS: In
49 patients, the catheter penetrated only the major pectoralis muscle. Only one
of these patients (2.0%) showed a loop. In 31 cases, the catheter went through
both the major and minor pectoralis muscle, and in 26 of these patients (83.9%),
a loop was seen. Complications after port implantation were catheter occlusion (n
= 2), pneumothorax (n = 2), thrombosis (n = 2), infection (n = 1), and catheter
dislocation (n = 1). CONCLUSIONS: The loop of catheter of central venous ports is
caused by catheter penetration through pectoralis major and minor.
PMID- 17035868
TI - Accuracy comparison of a 16 and 64 multidetector-row computed tomography scanner
to image small high-density structures.
AB - OBJECTIVES: The accuracy in imaging small high-density structures is compared for
16 and 64 multidetector-row computed tomography (MDCT) scanners. MATERIALS AND
METHODS: Phantom experiments and different quantification methods are used to
establish size measurement accuracy, object signal, and image noise, for both
MDCT systems. RESULTS: At similar scanning doses, image noise is larger (
approximately 55%) for the 64 MDCT compared with the 16 MDCT, leading to lower
signal-to-noise ratios ( approximately 28% for objects <2 mm). Object spread in
the xy-plane is similar for both systems; while it is reduced along the z-axis
(by approximately 0.18 mm) for the 64 MDCT. Measurement accuracy of the 64 MDCT
is not significantly higher (P < 0.05) compared with the 16 MDCT when using a
relative-threshold corresponding to 50% of the object maximum attenuation value.
However, when using a fixed-threshold, interscanner and interprotocol measurement
differences are statistically significant (eg, volume relative errors are reduced
by approximately 17% on average for the 64 MDCT). CONCLUSIONS: Measurement
accuracy of the 16 and 64 MDCT scanners is not significantly different when using
a 50% relative threshold. However, image noise is significantly larger for the 64
MDCT. Compared with a fixed-threshold based method, the 50% relative-threshold
strongly reduces interscanner and interprotocol measurement dependency and
improves accuracy.
PMID- 17035869
TI - Measurement of coronary artery bifurcation angles by multidetector computed
tomography.
AB - OBJECTIVE: Optimal stent deployment in coronary artery bifurcations requires
information about the angle between main vessel and side branch. We evaluated the
accuracy and interobserver variability of bifurcation angle measurements by
contrast-enhanced 16-slice multidetector computed tomography (MDCT) in comparison
with invasive angiography and examined the average angles of 4 main coronary
bifurcations. METHODS: To determine the accuracy of MDCT for measurement of
bifurcation angles, we scanned a coronary artery phantom containing 6
bifurcations (2-mm metal rods with angles between 25 degrees and 90 degrees )
using MDCT, and angles determined in the MDCT data set were compared with the
true values. To assess interobserver variability of angle measurements in
comparison to invasive angiography, the angles of 3 bifurcation sites (left
anterior descending and left circumflex coronary artery [LAD/LCX], LAD and first
diagonal branch [LAD/Diag 1], and posterior descending coronary artery and right
posterolateral branch [PDA/Rpld]) were determined in 15 patients both in 16
detector row MDCT data sets and invasive coronary angiograms by 2 independent
observers each. To assess the natural distribution of the 4 main coronary artery
bifurcation angles (LAD and LCX, LAD and Diag 1, LCX and OM1, PDA and Rpld), the
average angles of these bifurcations were determined in 16-slice MDCT data sets
acquired for coronary artery visalization in a group of 100 consecutive patients
with suspected coronary artery disease. RESULTS: The phantom study revealed a
mean difference between measured and true angles of 0.7 +/- 0.5 degrees . In the
comparison MDCT versus invasive angiography, the 45 angles were significantly
lager in MDCT (mean: 66 +/- 20 degrees vs. 56 +/- 24 degrees , P = 0.027).
Interobserver variability was significantly lower in MDCT (r = 0.91) than
invasive angiography (r = 0.62). Analysis of the natural distribution of
bifurcation angles by MDCT revealed average values of 80 +/- 27 degrees
(LAD/LCX), 46 +/- 19 degrees (LAD/Diag1), 48 +/- 24 degrees (LCX/OM1), and 53 +/-
27 degrees (PDA/Rpld), respectively. CONCLUSION: MDCT allows assessment of
coronary bifurcation angles with high accuracy, which may be of future potential
for planning interventional treatment.
PMID- 17035870
TI - 3 T contrast-enhanced magnetic resonance angiography for evaluation of the
intracranial arteries: comparison with time-of-flight magnetic resonance
angiography and multislice computed tomography angiography.
AB - PURPOSE: We sought to prospectively evaluate the image quality and visualization
of the intracranial arteries using high spatial resolution contrast-enhanced
magnetic resonance angiography (CE-MRA) at 3 T and to perform intraindividual
comparison with time-of-flight (TOF) MRA and multislice CT angiography (CTA).
MATERIALS AND METHODS: Twelve patients (5 men, 7 women, 37-71 years of age) with
suspected cerebrovascular disease prospectively underwent MRA and CTA. MRA was
performed on a 3 T MR system, including both 3-dimensional (3D) TOF (Voxel
dimension: 0.6 x 0.5 x 0.9 mm in 5 minutes and 40 seconds) and 3D CE-MRA (voxel
dimension: 0.7 x 0.7 x 0.8 mm in 20 seconds, using parallel acquisition with an
acceleration factor of 4). CTA images were acquired on a 16-slice CT scanner
(voxel dimension: 0.35 x 0.35 x 0.8 mm in 17 seconds). The image quality and
visualization of up to 26 intracranial arterial segments in each study was
evaluated by 2 experienced radiologists. The arterial diameter for selective
intracranial arteries was measured independently on each of the 3 studies, and
statistical analysis and comparative correlation was performed. RESULTS: A total
of 312 arterial segments were examined by CE-MRA, TOF-MRA, and CTA. The majority
of intracranial arteries (87%) were visualized with diagnostic image quality on
CE-MRA with a significant correlation to TOF (R values = 0.84; 95% confidence
interval 0.79-0.86, P < 0.0001), and to CTA (R values = 0.74; 95% confidence
interavl 0.68-0.78, P < 0.001). The image quality for small intracranial
arteries, including the anterior-inferior cerebellar artery, the posterior
communicating artery, and the M3 branch of the middle cerebral artery, was
significantly lower on CE-MRA compared with TOF and CTA (P < 0.03). There was a
significant correlation for the dimensional measurements of arterial diameters at
CE-MRA with TOF (r = 0.88, 95% confidence interval 0.81-0.93), and CTA (r = 0.83,
95% confidence interval 0.73-0.90). CONCLUSION: The described 3 T CE-MRA
protocol, spanning from the cervical to the intracranial vessels, visualized and
characterized the majority of intracranial arteries with image quality comparable
with that obtained using TOF-MRA and CTA. Further clinical studies are required
to establish the accuracy of the technique in a broader clinical setting.
PMID- 17035871
TI - Quantitative metrics for evaluating parallel acquisition techniques in diffusion
tensor imaging at 3 Tesla.
AB - OBJECTIVES: Single-shot echo-planar based diffusion tensor imaging is prone to
geometric and intensity distortions. Parallel imaging is a means of reducing
these distortions while preserving spatial resolution. A quantitative comparison
at 3 T of parallel imaging for diffusion tensor images (DTI) using k-space
(generalized auto-calibrating partially parallel acquisitions; GRAPPA) and image
domain (sensitivity encoding; SENSE) reconstructions at different acceleration
factors, R, is reported here. MATERIALS AND METHODS: Images were evaluated using
8 human subjects with repeated scans for 2 subjects to estimate reproducibility.
Mutual information (MI) was used to assess the global changes in geometric
distortions. The effects of parallel imaging techniques on random noise and
reconstruction artifacts were evaluated by placing 26 regions of interest and
computing the standard deviation of apparent diffusion coefficient and fractional
anisotropy along with the error of fitting the data to the diffusion model
(residual error). RESULTS: The larger positive values in mutual information index
with increasing R values confirmed the anticipated decrease in distortions.
Further, the MI index of GRAPPA sequences for a given R factor was larger than
the corresponding mSENSE images. The residual error was lowest in the images
acquired without parallel imaging and among the parallel reconstruction methods,
the R = 2 acquisitions had the least error. The standard deviation, accuracy, and
reproducibility of the apparent diffusion coefficient and fractional anisotropy
in homogenous tissue regions showed that GRAPPA acquired with R = 2 had the least
amount of systematic and random noise and of these, significant differences with
mSENSE, R = 2 were found only for the fractional anisotropy index. CONCLUSION:
Evaluation of the current implementation of parallel reconstruction algorithms
identified GRAPPA acquired with R = 2 as optimal for diffusion tensor imaging.
PMID- 17035873
TI - A summary of safety of gadofosveset (MS-325) at 0.03 mmol/kg body weight dose:
Phase II and Phase III clinical trials data.
AB - OBJECTIVE: We sought to summarize the Phase II and Phase III clinical trials
safety data for gadofosveset (Vasovist, MS-325), a new magnetic resonance
angiography contrast agent. MATERIALS AND METHODS: Subjects with known or
suspected vascular disease were administered 0.03 mmol/kg gadofosveset (767
subjects) or placebo (49 subjects) in phase II and phase III studies. Overall
safety data were pooled from 8 studies and included adverse event monitoring,
clinical laboratory assays, vital signs, oxygen saturation, physical examination,
and electrocardiography. The safety was monitored for 72 to 96 hours
postinjection (PI), and safety comparison with x-ray angiography using iodinated
contrast media also was performed in 318 subjects. In the phase II trial, 5 doses
of gadofosveset and placebo were evaluated. In this study, 38 patients were
administered placebo and 39 patients received 0.03 mmol/kg gadofosveset. RESULTS:
In pooled data, treatment related adverse events were reported by 176 (22.9%)
patients receiving gadofosveset and by 16 (32.7%) patients receiving placebo. In
phase II trial, treatment-related adverse events were reported by 13 of the 39
(33.3%) patients receiving gadofosveset and 9 of the 38 (23.7%) patients
receiving placebo. No severe or serious adverse events were reported in either
gadofosveset or placebo groups in this phase II trial. Pooled data revealed no
clinically significant trends in adverse events, laboratory assays, vital signs,
or oxygen saturation. A QTc prolongation of 2.8 milliseconds was observed at 45
minutes after MS-325 injection; however, this trend was similar to that of the
placebo group at the same time point (3.2 milliseconds). CONCLUSION: Gadofosveset
has exhibited a good safety profile and can be safely administered as an
intravenous bolus injection. The overall rate and experience of adverse events
was similar to that of placebo. The safety profile of gadofosveset is comparable
with that of other gadolinium contrast agents as reported in the literature.
PMID- 17035872
TI - Contrast-induced nephropathy in patients with chronic kidney disease undergoing
computed tomography: a double-blind comparison of iodixanol and iopamidol.
AB - BACKGROUND: Based on a single clinical trial, it has been suggested that the
contrast agent iodixanol, which is isotonic to human plasma, may be less
nephrotoxic than other nonionic contrast agents in renally impaired patients
after intra-arterial injection. We compared the effects on renal function of
iopamidol-370 injection (796 mOsm/kg) and iodixanol-320 (290 mOsm/kg) in patients
with chronic kidney disease undergoing contrast-enhanced multidetector computed
tomography (CE-MDCT) examinations using a multicenter, double-blind, randomized,
parallel-group design. METHODS: A total of 166 patients with stable moderate-to
severe chronic kidney disease (screening and baseline serum creatinine, SCr, > or
=1.5 mg/dL and/or creatinine clearance, CrCl, < or =60 mL/min) who were
undergoing CE-MDCT of the liver or peripheral arteries were randomized to receive
equi-iodine IV doses (40 gI) of either iopamidol-370 (370 mgI/mL) or iodixanol
320 (320 mgI/mL) at 4 mL/s. SCr and CrCl were obtained at screening, baseline,
and at 48-72 +/- 6 hours after dose (mean, 57.4 hours). Contrast-induced
nephropathy (CIN) was defined as an absolute increase > or =0.5 mg/dL (44.2
micromol/L) and/or a relative increase in SCr > or =25% from baseline. RESULTS: A
total of 153 patients were included in the final analysis (13 patients excluded
because of lack of follow-up, hemodialysis to remove contrast, average daily CrCl
variation >1% at screening). The 2 study groups were comparable with regard to
age, gender distribution, the presence of diabetes, concomitant medications,
hydration, and contrast dose. Mean predose SCr was 1.6 +/- 0.4 mg/dL in both
groups (P = 0.9). An absolute increase > or =0.5 mg/dL (44.2 micromol/L) in SCr
was observed in none of the patients receiving iopamidol-370 and in 2.6% (2/76)
of patients receiving iodixanol-320 (95% confidence interval -6.2, 1.0, P = 0.2).
A relative increase > or =25% in SCr occurred in 4% (3/77) of patients receiving
iopamidol-370 and in 4% (3/76) of the patients receiving iodixanol-320 (95%
confidence interval -6.2, 6.1, P = 1.0). CONCLUSION: The rate of CIN was
similarly low in risk patients after intravenous administration of iopamidol-370
or iodixanol-320 for CE-MDCT.
PMID- 17035874
TI - Operator-dependent reproducibility of size measurements of small phantoms and
lung nodules examined with low-dose thin-section computed tomography.
AB - OBJECTIVE: We sought to assess the reproducibility of size measurements of small
lung nodules examined with low-dose thin-section computed tomography (LDTSCT).
MATERIALS AND METHODS: Three radiologists measured volume with a semiautomatic
tool and diameters manually of 20 (equivalent diameter range, 5.3-11 mm) phantom
nodules and 37 (mean diameter range, 5-8.5 mm) lung nodules in subjects
undergoing LDTSCT. RESULTS: In phantoms, the worst 95% limits of agreement (95%
LA) for volume were -3.0% and 3.0% within operator and -3.1% and 2.8% between
operators. The coefficient of repeatability (CR) for diameter ranged between 0.51
and 0.67 mm within operator and the 95% LA were from -0.71 to 0.71 mm between
operators. In nodules, the worst intraoperator 95% LA for volume were -14.4% and
17.6% within operator and -13.1% and 14.2% between operators. The CR for diameter
ranged between 0.48 and 0.73 mm within operator and the 95% LA were from -1.16 to
1.16 mm between operators. CONCLUSION: Operator-dependent variability of size
measurements of small nodules examined with LDTSCT is not negligible and should
be considered in lung cancer-screening studies.
PMID- 17035875
TI - Future nursing administration graduate curricula, Part I: Call to action.
PMID- 17035876
TI - Expert opinion: challenges and opportunities for academic and organizational
partnership in evidence-based nursing practice.
PMID- 17035877
TI - The clinical nurse leader: a valued member of the healthcare team.
PMID- 17035878
TI - Nurses' perceptions of the advantages and disadvantages of their shift and work
schedules.
PMID- 17035879
TI - A new paradigm for information retrieval: InfoButton Access technology.
PMID- 17035880
TI - A road map for creating a Magnet work environment.
AB - OBJECTIVE: The authors examine the relationship between working environment and
the developmental level of the workforce, against the backdrop of the American
Nurses Credentialing Center Magnet Recognition Program, to provide a road map for
creating a positive work environment. BACKGROUND: With the daily demands on nurse
managers, there is a need to identify focused strategies to achieve a Magnetized,
high-performing work environment. METHODS: The American Nursing Association
Magnet survey was administered to nurses at a large healthcare system. Patient
units at each hospital were categorized as reactive, responsive, proactive, or
high performing. Similar categories of units across all 6 hospitals were
analyzed. Analysis of variance was performed on each Force of Magnetism by
developmental level. RESULTS: Mean scores measuring the Forces of Magnetism were
statistically significant between reactive and responsive units. Likewise, mean
scores between responsive and proactive units were also statistically
significant. Between reactive and responsive units, there were 3 statistically
significant forces of Magnetism: organizational structure, management style, and
interdisciplinary relations. These are labeled primary priority forces. Between
responsive and proactive units, there were 6 statistically significant forces of
Magnetism labeled secondary priority forces: policies and programs; professional
models of care; quality of care; consultation and resources; autonomy; and
interdisciplinary relations. CONCLUSIONS: Nursing staff perceive the "Magnetism"
of the work environment differently, depending on the developmental level of the
unit. Nurse managers with reactive units should focus on the 3 Forces of
Magnetism identified as the primary priority forces, in order to help develop
their unit to the next level of responsive. Once a responsive level has been
achieved, the next 6 forces should be addressed.
PMID- 17035881
TI - Improving nursing practice and patient care: building capacity with appreciative
inquiry.
AB - Appreciative inquiry is a philosophy and methodology for promoting positive
organizational change. Nursing leaders at 6 community hospitals are partnering
with the authors on a project that uses appreciative inquiry to improve
communication and collaboration, to increase nurse involvement in decision
making, and to enhance cultural awareness and sensitivity. In this article, the
authors describe appreciative inquiry, how hospitals are using it, and the
initial lessons learned.
PMID- 17035882
TI - Nurse executive and staff nurse perceptions of the effects of reorganization in
Veterans Health Administration hospitals.
AB - OBJECTIVE: To examine nurse executive perceptions of effects of service line
reorganization on nurse executive roles, nursing staff and patient care, and
compare nurse executive responses to staff nurse reports of job satisfaction and
quality of care in the same types of Veterans Health Administration facilities.
BACKGROUND: Although a growing body of research focuses on the association
between nurse staffing structures, nurse satisfaction, and patient outcomes,
relatively little attention has been paid to the effects of hospital
restructuring on nursing management and nursing staff. METHODS: Data on hospital
and nursing service organization and nurse executive perceptions were collected
through structured interviews with 125 nurse executives conducted from December
2002 through May 2003. Staff nurse data were derived from a survey of Veterans
Health Administration nursing staff conducted from February through June 2003 at
the same facilities. RESULTS: Nurse executives in Veterans Health Administration
described significant changes in the nurse executive role, and new challenges for
managing nursing practice and achieving consistent quality of nursing care.
Although nursing management perceived differences in the overall effects of
restructuring on nursing staff depending on the type of reorganization, staff
nurses reported significant differences in perceived quality of patient care
across organization types.
PMID- 17035883
TI - Excellence through evidence: the what, when, and where of clinical autonomy.
AB - Despite high valuation and persistent challenges to nurses to function
autonomously, neither the structures fostering clinical autonomy nor the
relationship between autonomous practice and positive patient outcomes has been
empirically established. Much of this is caused by the lack of precision in
definition and measurement of the concept and identification of autonomy-enabling
structures. The goal of this multisite, evidence-based management practice study
is to provide an in-depth analysis of the concept and an articulation of a
grounded theory of clinical autonomy preparatory to the identification of
structures supporting autonomy. This article describes the research design and
methodology and explicates the grounded theory by answering the following
questions: What is clinical autonomy? When and where does it occur? Suggestions
and recommendations for what could be done to clarify the concept and promote
clinical autonomy are provided.
PMID- 17035884
TI - Retaining older nurses in bedside practice.
PMID- 17035886
TI - Implementation of a written protocol for management of central venous access
devices: a theoretical and practical education, including bedside examinations.
AB - The objectives of this study were to evaluate registered nurses' (RN) compliance
with a local clinical central venous access device (CVAD) protocol after
completing an educational program and to determine RNs' perception of the
program. Seventy-five RNs working in hematology participated in the educational
part of the program. Sixty-eight RNs were examined while changing CVAD dressings
or placing a Huber needle into a port on actual patients. Sixty percent of the
RNs passed the examination and reported that the program increased their
knowledge. The results indicated that the educational program could be
recommended for use when implementing a new clinical protocol.
PMID- 17035887
TI - The role of albumin in fluid and electrolyte balance.
AB - Albumin plays an important role in maintaining homeostasis within the body and
depends on the cell membrane and the transport mechanism, including diffusion,
osmosis, filtration, and active transport. The dissolved proteins, which are the
only substances that do not penetrate the pores of the capillary membrane, are
responsible for the osmotic pressure of the capillary membrane. Approximately 75%
of the total colloid osmotic pressure is related to albumin.
PMID- 17035888
TI - Ethical decision-making when caring for the noncompliant patient.
AB - Ethical dilemmas frequently occur when nurses care for patients with a history of
intravenous substance abuse who are hospitalized on medical-surgical units. This
article discusses the recent findings on substance abuse, including its impact on
the brain, effects on society and healthcare, available treatment options, and
medical complications related to substance abuse. An ethical model is introduced
to analyze ethical dilemmas with an accompanying case scenario. Resources
available to nursing staff in many healthcare settings are identified as well as
strategies to improve nursing care for this challenging population. The purpose
of this article is to reduce nurses' feelings of frustration and stress in order
to improve their morale. Finally, this particular contemporary ethical issue will
be viewed as if perceived by Florence Nightingale.
PMID- 17035889
TI - Vasculitis and biologic infusion therapies: implications for nursing.
AB - Vasculitis is a heterogeneous group of uncommon, complex rheumatologic diseases.
These diseases are known for their high mortality and morbidity rates due to the
underlying disorders themselves, as well as complications of their conventional
treatments. Oral and intravenous glucocorticosteroids and other immunosuppressive
agents such as cyclophosphamide, methotrexate, and azathioprine are used to
manage these diseases. These therapies are effective, but they have a global
impact (often negative) on patients' immune systems and cause a number of
nonimmunologic toxicities. They also are ineffective in inducing long-term
remissions. Novel biologic infusion agents such as rituximab and infliximab are
being prescribed off-label for some patients with vasculitis who have failed to
respond to conventional therapy or because there are contraindications to
standard-of-care treatments. This article provides an orientation to vasculitis,
its standard of care, infusion biologics under investigation in these diseases,
and the nursing implications for infusion professionals.
PMID- 17035890
TI - Update on the management of chemotherapy-induced nausea and vomiting.
AB - Chemotherapy is associated with a variety of side effects, and many of these can
be dose-limiting. One of the most dreaded side effects for patients receiving
chemotherapy is nausea and vomiting, however. Although in the last 2 decades
there have been several advances in the development of new therapies for
prevention of chemotherapy-induced nausea and vomiting (CINV), recent
pharmacologic advances have significantly improved control of this feared side
effect. Antiemetic guidelines help clinicians manage CINV and are updated
frequently. Ongoing studies further define appropriate management of patients
with CINV; of particular interest is delayed nausea and vomiting. With the
addition of the long-acting serotonin antagonist, palonosetron, and the unique
neurokinin-1 antagonist, aprepitant, control of CINV has improved considerably
for those patients receiving chemotherapy. This article discusses CINV and recent
pharmacologic advances in controlling this side effect. Guidelines for the
management of CINV are reviewed.
PMID- 17035893
TI - Youth development is a public health approach. Introduction.
PMID- 17035894
TI - Healthy youth development: science and strategies.
AB - Research over the past decade indicates that healthy youth development strategies
the deliberate process of providing all youth with the support, relationship
experiences, resources, and opportunities needed to become successful and
competent adults-are promising approaches for preventing or reducing a wide range
of adolescent health-risk behaviors. In this article, we describe the history,
science, and practice of healthy youth development. First, a brief overview of
barriers to healthy youth development including obstacles the United States will
face in the coming decades for meetings the needs of all youth is provided. We
present the history of resiliency research that illuminated the concepts "risk
factors," "protective factors," and "healthy youth development," and provide
definitions of each of these concepts. Next, we discuss select empirical evidence
supporting youth development strategies and highlight the events and experiences
in the lives of youth that have been consistently shown to protect youth against
a broad range of health-risk behaviors. Finally, we describe elements of
effective interventions for promoting the healthy development of all young
people.
PMID- 17035896
TI - Management matters: sustaining funds for youth development programs.
AB - Drawing on data collected through evaluations of youth development (YD) programs,
including those offered in community-and school-based after-school programs, this
article describes practices that support program managers' quests for funds that
will sustain programs. Designing YD activities to incorporate skills building
(including educational) and recreational and fun activities for adolescents can
enlarge the resource pool to include funds for educational activities and youth
engagement. Strong behavioral management of programs encourages youth attendance
and provides a safe environment to develop positive peer and adult relationships,
both of which are crucial to YD. Strong attendance, in turn, can keep program
costs in line with expectations and reduce the marginal costs for additional
participants. Faithful implementation of previously tested program models
increases the likelihood that the program will be effective, and positive
outcomes are essential to sustained funding.
PMID- 17035897
TI - Youth development as a "big picture" public health strategy.
PMID- 17035898
TI - Terms of engagement: aligning youth, adults, and organizations toward social
change.
AB - Youth engagement is widely accepted as an essential element of successful youth
development activities at an organizational level. However, because the practical
issue of how to engage youth in the work of organizations remains unsettled, this
qualitative research study was conducted as an outgrowth of consultation by Youth
Infusion (a youth organization that works to support youth as decision makers,
advocates, and community change agents) requested by two youth-serving
governmental agencies. Organizational structures, processes, and cultures that
might support youth engagement were the focus of two research questions: (1) What
accounts for differences in an organization's youth-adult engagement outcomes;
and (2) What strategies can organizations adopt to maximize the likelihood of
successful outcomes? Participatory action research drove the design and
implementation of data collection and analysis. Five elements were related to
successful youth engagement: (1) strong external advocacy coalitions; (2)
alignment of management and staff; (3) clear, consensus-driven visions; (4) an
openness to change; and (5) unified values. Organizations interested in advancing
youth engagement in their daily operations should consider attending to these
elements in their strategic planning.
PMID- 17035899
TI - Comprehensive statewide approach to improve youth outcomes: experience of the New
York State Youth Development Team.
AB - Best practice research indicates a need for a policy shift toward positive youth
development (YD) principles and strategies. The New York State Youth Development
Team (YDT) is a public-private partnership of leading agencies whose holistic
vision, "families, schools and communities partner to support the development of
healthy, capable and caring youth," requires key stakeholders at all levels to
address adverse youth health outcomes through effective partnerships. To
transform the YDT vision into statewide practice requires committed actions
(policy, funding, and training) at the state and community levels. Key lessons
learned and experience-based recommendations that guide YD efforts in New York
State can help state and local agencies move more to a positive YD approach that
helps young people become healthy, caring, competent, and contributing adults,
fully prepared to be parents, workers, leaders, entrepreneurs, and citizens of
the future.
PMID- 17035900
TI - Adolescent health and youth development: turning social policy into public health
practice.
PMID- 17035902
TI - Youth development is a public health approach. Don't make decisions about us,
without us.
PMID- 17035901
TI - New York State's "Assets Coming Together (ACT) for Youth": a statewide approach
effects community change.
AB - The New York State Department of Health launched an innovative initiative, Assets
Coming Together (ACT) for Youth, implemented in 2000, as a public health strategy
to promote youth development (YD) as a means to improve health outcomes for
youth. ACT for Youth shifted the focus from problems and problem reduction to
assets and strength-based means of improving health by enhancing opportunities
and supports in communities for all youth and their families. ACT for Youth is
innovative in its emphasis on community building and community change at multiple
levels. This descriptive report mentions development, implementation, specific
objectives, and highlights of accomplishments in mobilizing communities around
YD. Lessons learned over the first 5 years of the initiative are reviewed, with
emphasis on the elements of successful health department YD programming. From
this foundation, New York State hopes to be in the vanguard of utilizing YD as a
public health improvement strategy and hopes that others will follow.
PMID- 17035903
TI - Building effective community partnerships for youth development: lessons learned
from ACT for Youth.
AB - Assets Coming Together (ACT) for Youth is a community-based, public health youth
development (YD) initiative across New York State. Diverse community partnerships
and a wide range of community settings have participated in this statewide
effort, providing a rich laboratory to study effective partnership development.
Based on the experience of the first 6 years of ACT for Youth, this report
discusses lessons learned in partnership development in ACT for Youth with
attention to the most effective partnerships. The most effective partnerships
were differentiated by their ability to accomplish four tasks: (1) clearly define
the purpose and vision of the initiative, (2) establish a community development
partnership organizational structure and membership, (3) develop collaborative
work processes, and (4) create sustained momentum. These elements will receive
close attention in future YD efforts in New York State, and should be used to
inform YD efforts in other states or communities.
PMID- 17035904
TI - Come on back: enhancing youth development through school/community collaboration.
AB - With the implementation of the federal "No Child Left Behind" Education Act,
schools in America are under increased pressure to demonstrate academic success
through higher test scores. Academic leaders are increasingly recognizing that
the issues that students confront are not unique to the school setting but are
issues of the larger community. Stronger links need to be forged between those
working with our youth in schools and those providing needed services in the
community. The following case study describes "Come On Back," an after-school
program in Utica, New York, that targets students who are most at risk for
dropping out of school and experiencing academic failure. The students were
involved both as participants and planners for Come On Back activities. This
collaboration applied youth development principles to improve young people's
connection to school. Come On Back provides an example of how youth development
partnerships between schools and communities can also be used to improve academic
performance.
PMID- 17035905
TI - Capacity-building for youth workers through community-based partnerships.
AB - Although positive youth development (PYD) is increasingly influential in the
field of youth programming, core knowledge and competencies for youth workers
continue to be defined. Youth serving agencies throughout the United States face
serious obstacles in the creation of a stable and well-trained workforce, despite
the presence of many talented and resourceful individuals who work with youth in
the community. One strategy for organizational and staff development is through
PYD-oriented, community-based partnerships designed to enhance youth worker
knowledge and competence. Two different partnerships are described in this
report. The first brought together experts in youth work, health, and trauma, and
focused on improving youth worker response to psychologic trauma commonly
experienced by urban youth. This partnership used an iterative reflective
practice approach to describe best practices in youth work. The second
partnership strategically taught evaluation skills to youth program consumers,
AmeriCorps service members, and adult youth workers to advance youth-adult
partnerships. These exemplars demonstrate that partnerships can drive systems for
improving competencies in youth workers and the capacities of youth services.
PMID- 17035906
TI - Youth development and prevention.
PMID- 17035907
TI - Selecting statewide youth development outcome indicators.
AB - This article presents the process used to develop a set of statewide positive
youth development (YD) outcome indicators to complement existing adolescent well
being indicators in New York State (NYS). Intended uses included program and
community-, county-, and state-level planning; grant writing; evaluation; and
outcome monitoring in coordination with national YD-oriented initiatives. A
common set of metrics, if adopted, would promote consistency and information
sharing across levels and purposes. A workgroup of the NYS Youth Development Team
reviewed existing indicators and accepted nominations from NYS stakeholders.
Input from Youth Development Team members and national YD experts was used to
narrow the list to 91. Forty-one NYS policy makers performed card sorts and
ratings of the indicators, and a concept-mapping process, employing hierarchical
cluster analysis, identified nine clusters of items. The policy makers, along
with 121 NYS program providers and 91 young adults (aged 18-21) rated the
indicators from 1 ("not important") to 5 ("very important"). All intergroup
correlations of ratings were 0.93 or greater, and therefore responses were
analyzed together. The concept map and mean indicator ratings were used to select
a short list of 15 indicators. Although respondents were intentionally given a
mix of problem-focused, risk-focused, and strength-based items, the highest rated
items were almost exclusively strength based.
PMID- 17035908
TI - Engaging youth in participatory research and evaluation.
AB - Although participatory research has been applied by a wide range of disciplines,
the engagement of youth as partners in research and evaluation efforts is
relatively new. The positive youth development movement has influenced scholars
and practitioners to include youth as partners in the design and implementation
of research involving issues that affect their lives. Engaging youth in research
and evaluation not only generates useful knowledge for communities and
individuals but also provides opportunities for the development and empowerment
of youth participants, leading to benefits for young people, organizations, the
broader community, and the research process. However, there has been little
systematic study to establish an evidence base for these effects. This article
describes four projects that illustrate active youth participation in research.
These examples demonstrate opportunities for positive youth development, create a
context for intergenerational partnerships, and generate research findings to
inform future interventions and organizational improvements, including community
mobilization.
PMID- 17035909
TI - Measuring youth development outcomes for community program evaluation and quality
improvement: findings from Dissemination of the Rochester Evaluation of Asset
Development for Youth (READY) tool.
AB - PURPOSE: The Rochester Evaluation of Asset Development for Youth (READY) is a
brief program-controlled evaluation and quality improvement tool used for
assessment of four developmental assets for youth: caring adult relationships,
basic social skills, decision making, and constructive use of leisure time. This
article reports on the early implementation and combined benchmark data generated
from the use of the READY tool by community-based youth-serving agencies in
Rochester, New York. METHODS: Nine youth-serving agencies used the 40-item READY
tool in 2002-2003. In addition to individual program evaluation and quality
improvement, a combined dataset was developed and analyzed to establish community
benchmarks. Program leaders' qualitative feedback on their experience with the
READY tool is also reviewed. RESULTS: 1,070 youth participated. Those youth who
reported feeling more connected to the programs in which they participated and
having more active and frequent participation had consistently higher scores on
measured outcomes. Overall, most agencies required some technical assistance to
first field READY. Most agencies successfully used their own data to address
program quality improvement, and reported being happy with their ability to do
so. DISCUSSION: READY is a promising tool for measuring community-based program
attributable positive developmental outcomes for youth.
PMID- 17035910
TI - Targeting evaluations of youth development-oriented community partnerships.
AB - Community-based partnerships (CBPs) focused on youth development (YD) have the
potential to improve public health outcomes. These partnerships also present
opportunities for the design and implementation of innovative, community-level
change strategies, which ultimately may result in new capacities for positive YD.
Evaluation-driven learning and improvement frameworks facilitate the achievement
of these partnership-related benefits. Partnerships are complex because they
embody multiple levels of intervention (eg, youth-serving programs, youth
participation as partners or evaluators, network development for collaborative
projects and resource sharing, YD-oriented organizational or community policy
change). This inherent complexity transfers to evaluations of CBPs. This article
provides resources for meeting evaluation-related challenges. It includes a
framework for articulating relevant evaluation questions for YD-oriented CBPs, a
summary of relevant types of evaluation studies, and practical solutions to
common evaluation problems using targeted evaluation studies. Concrete examples
of relevant, small-scale evaluation studies are provided throughout.
PMID- 17035913
TI - The perioperative implications of obstructive sleep apnea.
AB - Patients with obstructive sleep apnea provide significant challenges to the
perioperative team. This disorder is often undiagnosed and coexists with other
disease processes such as hypertension, congestive heart failure, and cor
pulmonale. The prevalence of obesity in American society suggests that an
increasing number of patients with sleep apnea will present for surgery. During
the perioperative period, life-threatening problems can occur during anesthetic
induction and emergence. The pathophysiology of obstructive sleep apnea is
reviewed here along with the anesthesia implications of this disease process.
Members of the perioperative team need to be aware of the implications of sleep
apnea so that surgical outcomes can be optimized.
PMID- 17035915
TI - Impact of external fixation on adolescents: an integrative research review.
AB - PURPOSE: To define the state of nursing knowledge about the psychological impact
of treating adolescents with external fixation devices (EFDs). METHOD: An
integrated research review was conducted on literature available from CINAHL,
MEDLINE, and PsycINFO. Keywords used were external fixation, fracture fixation,
orthopaedic or orthopaedic, limb lengthening, Ilizarov, halo traction, Orthofix,
EBI fixator, pelvic fixator, ring fixator, body image, self-concept, self-esteem,
self-perception, adaptation, emotional, behavior, and outcome. Inclusion criteria
for studies were (a) publication from 1990 to 2003, (b) focus on psychosocial and
functional outcomes of treating adolescents with EFDs, and (c) publication in
English. Studies were categorized by author, year, discipline(s), design, focus,
sample, measurement, findings, and research recommendations. Findings and
recommendations were compared across publications. RESULTS: All studies reported
psychological and behavioral changes after EFD treatment. Pain and pin-site
infections were the most problematic physical findings. Depression was
universally evident to varying degrees, with some suicidal ideation and self
destructive behaviors, although mostly reported as transient. This predominantly
retrospective cohort of studies reported social isolation as well as eating and
sleep disturbances. Family and nursing support, a multiple disciplinary approach,
and better preoperative preparation were crucial to adolescents psychological
health after EFD treatment. CONCLUSION: Adolescents treated with EFDs require
significant psychosocial support. The findings reveal major gaps in the knowledge
on adolescents treated with external fixation for traumatic injury and none
focused on EFD treatment in the acute period.
PMID- 17035917
TI - Broken bones: common pediatric upper extremity fractures--part II.
PMID- 17035919
TI - e-Knee: the electronic knee prosthesis.
AB - Tibiofemoral forces determine polyethylene wear and affect the longevity of total
knee prostheses. Previously, investigators relied on theoretic data from
mathematical models to predict mechanical forces in the knee. Predictions of
tibiofemoral forces are highly variable because of the complex interplay of the
muscles involved in activities. Ideally, knee forces should be directly measured.
An electronic total knee prosthesis (e-Knee) was developed to directly measure
tibiofemoral compressive and tensile forces in vivo. After 13 years of research
and development, the e-Knee was implanted into a patient in 2004. Tibiofemoral
force data were collected intraoperatively and throughout the postoperative
period during activities of daily living and during exercise. Direct measurement
of knee forces can lead to a better understanding of the stresses seen following
total knee arthroplasty. Information generated by the e-Knee will aid in the
improvement of implant design and patient care.
PMID- 17035921
TI - Patient Education Corner. Accessing and evaluating the Internet for patient and
family education.
AB - In the last decade, the Internet has become a vast resource for healthcare
information. Multiple Web sites, produced by the federal government, healthcare
institutions, and individual healthcare providers, give Americans a wealth of
useful information sources. Nurses recognize that more Americans than ever before
are using the Internet and that nurses are in an excellent position to help
patients learn how to search for healthcare topics and evaluate the information
found. This article will focus on seeking information, judging the quality of the
information, and listing specific Web sites.
PMID- 17035922
TI - Managing insomnia.
AB - Sleep is a vital part of normal health and wellness for everyone. It is also an
important factor in recovering from the physiological and emotional stress of any
hospitalization or illness. Insomnia--the lack of adequate period of sleep--has a
profound impact on society and public health in many ways. Chronic insomnia
contributes to injury and illness and may have adverse effects on cognitive
functioning, interpersonal relationships, concentration, the ability to handle
stress, and productivity. Nurses who are knowledgeable about the possible causes
of insomnia, the different types of insomnia, and various therapeutic
interventions will be able to identify those who have insomnia or are at risk of
insomnia and will be able to counsel these patients about healthy sleep habits
and the safe use of pharmacotherapeutic therapies used to treat insomnia.
PMID- 17035924
TI - Osteogenic sarcoma.
PMID- 17035926
TI - Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity
limitation--United States, 2003-2005.
AB - Arthritis is highly prevalent among U.S. adults, the leading cause of disability,
and associated with substantial activity limitation, work disability, reduced
quality of life, and high health-care costs. As the population ages, arthritis is
expected to affect an estimated 67 million adults in the United States by 2030.
This report updates estimates of the national prevalence of doctor-diagnosed
arthritis and arthritis-attributable activity limitation in the adult U.S.
population, using data from the National Health Interview Survey (NHIS) for 2003
2005. The findings indicated that an estimated 21.6% of the adult U.S. population
(46.4 million persons) had doctor-diagnosed arthritis, and 8.3% (17.4 million)
had arthritis-attributable activity limitations. Public and private health
agencies should promote measures to increase the availability of evidence-based
arthritis prevention and management interventions.
PMID- 17035927
TI - Update on vaccine-derived polioviruses.
AB - In 1988, the World Health Assembly resolved to eradicate polio worldwide. The
Global Polio Eradication Initiative (PEI) of the World Health Organization (WHO)
has led to a decline in global polio incidence, from an estimated 350,000 cases
in 1988 to fewer than 2,000 reported cases in 2005, and polio remains endemic to
only four countries (Afghanistan, India, Nigeria, and Pakistan). However, two
additional obstacles to global eradication involve vaccine-derived polioviruses
(VDPVs). Polio outbreaks continue to be associated with circulating vaccine
derived polioviruses (cVDPVs) in areas with low oral poliovirus vaccine (OPV)
coverage. In addition, long-term excretion of neurovirulent immunodeficiency
associated vaccine-derived polioviruses (iVDPVs) can lead to poliovirus spread to
contacts. Overcoming these obstacles is challenging. High rates of OPV coverage
will prevent all poliovirus spread, including spread of VDPVs, but will not
prevent establishment of prolonged VDPV infections in certain persons with B-cell
immunodeficiencies (i.e., having defects in antibody production). Inevitable gaps
in vaccination coverage will give rise to cVDPVs as long as OPV use continues.
This report updates a previous report on VDPVs and describes the potential
implications of VDPVs in the final stages of global polio eradication. The
findings underscore the critical need to strengthen strategies to prevent
emergence of VDPVs and to stop all OPV use once wild polioviruses (WPVs) are
eradicated.
PMID- 17035928
TI - West Nile virus activity--United States, January 1-October 10, 2006.
AB - This report summarizes West Nile virus (WNV) surveillance data reported to CDC
through ArboNET as of 3 a.m. Mountain Daylight Time, October 10, 2006. A total of
41 states and the District of Columbia had reported 3,135 cases of human WNV
illness to CDC. A total of 1,717 (55%) cases for which such data were available
occurred in males; median age of patients was 50 years (range: 3 months-99
years). Dates of illness onset ranged from January 6 to September 25; a total of
97 cases were fatal.
PMID- 17035929
TI - Botulism associated with commercial carrot juice--Georgia and Florida, September
2006.
AB - On September 8, 2006, the Georgia Division of Public Health (GDPH) and CDC were
notified of three suspected cases of foodborne botulism in Washington County,
Georgia. On September 25, the Florida Department of Health and CDC were notified
of an additional suspected case in Tampa, Florida. This report describes the
joint investigation and control measures undertaken by state and local health
departments, CDC, and the Food and Drug Administration (FDA).
PMID- 17035930
TI - Gestational methylazoxymethanol acetate treatment impairs select cognitive
functions: parallels to schizophrenia.
AB - Gestational methylazoxymethanol acetate (MAM) exposure has been suggested to
produce neural and behavioral abnormalities similar to those seen in
schizophrenia. In order to assess MAM treatment as a model of schizophrenia,
pregnant female rats were injected with MAM (22 mg/kg) on gestational day 17 and
their offspring were assessed in adulthood on a series of cognitive tasks. The
first experiment involved an attentional set-shifting task, a rodent analog of
the Wisconsin card sort task. In experiment 2, animals were tested on the 5
choice serial reaction time task, a rodent analog of the continuous performance
task. In the final experiment animals were assessed on a differential
reinforcement of low rate of responding 20 s schedule of reinforcement (DRL-20),
a task that is sensitive to changes in inhibitory control. In the first
experiment, MAM-treated animals required a greater number of trials than controls
to successfully learn an extradimensional shift on the set-shifting task, and had
difficulties in learning to reverse a previously acquired discrimination. In
contrast, MAM-treated animals showed little impairment on the 5-choice task,
aside from a modest but consistent increase in premature responding. Finally, MAM
exposed animals showed substantial impairments in DRL performance. Post-mortem
analysis of brain tissue showed significant decreases in tissue weight in the
hippocampus, parietal cortex, prefrontal cortex, and dorsal striatum of MAM
treated animals. These results support the notion that MAM treatment may simulate
some aspects of schizophrenic cognition.
PMID- 17035931
TI - Enduring deficits in sustained visual attention during withdrawal of intravenous
methylenedioxymethamphetamine self-administration in rats: results from a
comparative study with d-amphetamine and methamphetamine.
AB - Although amphetamine-derived stimulants are widely associated with neurotoxicity,
it is poorly understood whether extended exposure to such drugs produces lasting
effects on neurocognitive function. This study investigates whether chronically
self-administered d-amphetamine, methamphetamine (MA), or
methylenedioxymethamphetamine (MDMA) leads to residual deficits in a rodent test
of sustained visual attention and impulsivity. Rats were trained on a five-choice
serial reaction time task and subsequently trained to self-administer d
amphetamine, MA, or MDMA (all 50 microg/infusion), intravenously, for 3 weeks.
Effects on performance were evaluated 24 h after drug discontinuation and for
several weeks thereafter, including various challenge sessions to increase the
attentional demands of the task. The results indicate divergent patterns of self
administration among the three drugs tested with increasing rates of intake
evident in rats self-administering amphetamine, but not MA, and widely
fluctuating rates in the MDMA group. Withdrawal of MA resulted in severe
behavioral disturbances, with significant effects on accuracy, omissions,
response latency, and impulsivity that lasted up to 2 weeks in some cases.
Amphetamine and MDMA withdrawal were associated with similar, but shorter-lasting
effects on performance. However, when challenged with a high event rate session 6
weeks after drug discontinuation, rats previously exposed to MDMA continued to
show deficits in the accuracy and speed of responding. These findings show that
amphetamine-derived stimulants have both short- and long-term consequences for
psychomotor functioning. The demonstration of residual deficits in rats
chronically exposed to MDMA raises some concern about the potential harm caused
by this drug in human ecstasy users.
PMID- 17035932
TI - Blockade of the mineralocorticoid receptor in healthy men: effects on
experimentally induced panic symptoms, stress hormones, and cognition.
AB - Animal studies have shown that blockade of central mineralocorticoid receptors
(MR) has anxiolytic effects and impairs several aspects of cognitive function. No
study to date assessed the effects of MR blockade on anxiety and cognitive
function in humans. In the present study, 16 healthy young men were treated
either with placebo or with 300 mg spironolactone, a MR-antagonist, at 1100,
1330, and 1630 hours in a balanced cross-over design with the two study
conditions being 1 week apart. At 1500 hours, the panic symptoms provoking
compound cholecystokinin-tetrapeptide (CCK-4) was administered i.v. on both
occasions and panic symptoms were assessed. We measured plasma ACTH and cortisol
between 1300 and 1900 hours and assessed cognitive function between 1800 and 1900
hours. CCK-4 elicited panic symptoms and increased ACTH and cortisol secretion in
both conditions. Intensity of panic symptoms after CCK-4 was not different
between spironolactone and placebo. Spironolactone significantly impaired
selective attention and delayed recall of visuospatial memory, and diminished set
shifting/mental flexibility on a trend level. Pretreatment with spironolactone
led to higher baseline cortisol levels compared to placebo whereas no differences
in stimulated cortisol, baseline ACTH, and stimulated ACTH emerged. Blockade of
MR with spironolactone increases baseline cortisol secretion and impairs
cognitive function but has no effect on experimentally induced panic symptoms in
humans, for the study design and dosage of spironolactone used. The domains of
cognitive function that are impaired after blockade of MR in men, that is,
selective attention, visuospatial memory, and mental flexibility/set shifting
appear to be remarkably similar to those described in animal studies.
PMID- 17035933
TI - Placebo-controlled trial comparing intermittent and continuous paroxetine in
premenstrual dysphoric disorder.
AB - Serotonin reuptake inhibitors (SRIs) do not have to be administered continuously
to be effective for premenstrual dysphoric disorder (PMDD), but can be given
during luteal phases only. This is of practical importance, but also of
theoretical interest since it suggests that the onset of action of SRIs is
shorter in PMDD than in, for example depression. In this study, both continuous
and intermittent SRI administration was compared with placebo, with the special
purpose of analyzing if different PMDD symptoms respond differently depending on
the treatment regimen. To this end, women meeting slightly modified DSM-IV
criteria for PMDD (mean+/-SD age, 37+/-6.3 years) were treated for three
menstrual cycles with paroxetine continuously, paroxetine during the luteal phase
only, or placebo, the population completing at least one treatment cycle
comprising 55-56 subjects per group. Continuous treatment with paroxetine reduced
premenstrual symptoms effectively with a response rate of 85%. The effect size
was highest for irritability (1.4) and lowest for lack of energy (0.5).
Intermittent treatment was as effective as continuous treatment in reducing
irritability, affect lability, and mood swings, but had a somewhat weaker effect
on depressed mood and somatic symptoms. The study indicates that the response
rate when treating PMDD with SRIs is high, and that irritability is a key target
symptom. Symptoms such as irritability, affect lability, and mood swings appear
to be more inclined to respond rapidly to SRIs, enabling intermittent treatment,
than are, for example, the somatic symptoms.
PMID- 17035934
TI - Acute effects of atypical antipsychotics on whole-body insulin resistance in
rats: implications for adverse metabolic effects.
AB - Although it is generally accepted that atypical antipsychotics differ in their
risk for diabetic side effects, the underlying pharmacological mechanisms are
unknown. Studies on the mechanisms of antipsychotic-induced hyperglycemia or
insulin resistance are often confounded by the concomitant weight gain and
dyslipidemia, known diabetic risk factors. To investigate whether antipsychotics
can acutely cause metabolic effects before any change in body composition, we
studied the effects of four atypical antipsychotics on whole-body insulin
resistance. Using the hyperinsulinemic, euglycemic clamp technique in conscious
rats, insulin and somatostatin were infused at a constant rate to provide
constant hyperinsulinemia and to suppress pancreatic insulin secretion. Glucose
was infused at a variable rate, adjusted to maintain euglycemia. At steady state,
animals were administered vehicle (V) or antipsychotic and the glucose infusion
rate was monitored as an index of insulin sensitivity. Clamp experiments using
radiotracers and studies on glucose uptake into isolated skeletal muscle were
conducted to differentiate between effects on hepatic glucose production (HGP)
and on peripheral glucose uptake. Olanzapine (OLAN) and clozapine (CLOZ) acutely
impaired whole-body insulin sensitivity in a dose-dependent manner (P<0.001 vs
V), whereas ziprasidone and risperidone had no effect. CLOZ also induced profound
insulin resistance after dosing 10 mg/kg/day for 5 days (P<0.05 vs V). Tracer
studies indicated that acute changes mainly reflect increased HGP, consistent
with the lack of effect on glucose uptake. OLAN and CLOZ can thus rapidly induce
marked insulin resistance, which could contribute to the hyperglycemia and
ketoacidosis reported for patients receiving those therapies.
PMID- 17035935
TI - The interface of oxytocin-labeled cells and serotonin transporter-containing
fibers in the primate hypothalamus: a substrate for SSRIs therapeutic effects?
AB - Oxytocin (OT) is a neuropeptide synthesized in the paraventricular (PVN) and
supraoptic nuclei (SON) in the hypothalamus. Although OT is more commonly known
for its role in the milk-ejection reflex, in recent years research has indicated
that OT participates in the expression of social behavior, memory processing,
modulation of fear, and stress responses. The demonstration that OT influences
affiliative behaviors, such as parental care and reproduction, and decreases
anxiety has lead to speculations that it may have a role in mood disorders.
Evidence from pharmacologic studies, pointing out the modulation of the OT system
by serotonin, has argued in favor of OT as a mediator of serotonin reuptake
inhibitors (SSRIs) antidepressant properties. In the present study, we
investigated the distribution and overlap of OT-labeled cells and serotonin
transporter (5-HTT) immunoreactive (IR) fibers in the Macaque hypothalamus,
utilizing immunocytochemical and double-immunofluorescent techniques. Consistent
with previous reports, the distribution of OT-labeled cells in the hypothalamus
is confined to the PVN and SON. In these nuclei, we demonstrate that the
distribution of 5-HTT-labeled fibers follows the distribution of OT-labeled
cells. Overlap of OT-labeled neurons and 5-HTT-IR fibers occurs in the
parvicellular, magnocellular, dorsal, and posterior subdivisions of the PVN. In
the SON, 5-HTT-labeled fibers and OT-labeled cells overlap in the ventromedial
subdivision and in the 'capsular' part of the dorsolateral SON. These findings
provide neuroanatomic support for the idea that SSRIs' therapeutic effects on
social affiliation and anxiety may be mediated in part through components of the
OT system.
PMID- 17035936
TI - Puromycin aminonucleoside induces oxidant-dependent DNA damage in podocytes in
vitro and in vivo.
AB - A decline in podocyte number correlates with progression to glomerulosclerosis. A
mechanism underlying reduced podocyte number is the podocyte's relative inability
to proliferate in response to injury. Injury by the podocyte toxin puromycin
aminonucleoside (PA) is mediated via reactive oxygen species (ROS). The precise
role of ROS in the pathogenesis of PA-induced glomerulosclerosis remains to be
determined. We sought to examine whether PA-induced ROS caused podocyte DNA
damage, possibly accounting for the podocyte's inability to proliferate in
response to PA. In vitro, podocytes were exposed to PA, with or without the
radical scavenger 1,3-dimethyl-2-thiourea (DMTU). In vivo, male Sprague-Dawley
rats were divided into experimental groups (n = 6/group/time point): PA, PA with
DMTU, and control, killed at days 1.5, 3, or 7. DNA damage was measured by DNA
precipitation, apurinic/apyrimidinic site, Comet, and 8-hydroxydeoxyguanosine
assays. Cell cycle checkpoint protein upregulation (by immunostaining and Western
blotting), histopathology, and biochemical parameters were examined. DNA damage
was increased in cultured podocytes that received PA, but not PA with DMTU. PA
exposure activated specific cell cycle checkpoint proteins, with attenuation by
DMTU. DNA repair enzymes were activated, providing evidence for attempted DNA
repair. The PA-treated animals developed worse proteinuria and histopathologic
disease and exhibited more DNA damage than the DMTU pretreated group. No
significant apoptosis was detected by terminal deoxynucleotidyl transferase
mediated dUTP nick end-labeling staining. A mechanism underlying the lack of
podocyte proliferation following PA-induced injury in vitro and in vivo may be
ROS-mediated DNA damage, with upregulation of specific cell cycle checkpoints
leading to cell cycle arrest.
PMID- 17035937
TI - Glomerular involution in children with frequently relapsing minimal change
nephrotic syndrome: an unrecognized form of glomerulosclerosis?
AB - Global glomerulosclerosis can be divided in the vascular (obsolescent) type and
the glomerulopathic (solidified) type. In biopsies from children with recurrent
nephrotic syndrome owing to minimal change nephropathy (MCN), we noticed small,
globally sclerosed glomeruli that appeared to be distinct from global
glomerulosclerosis. These small sclerosed glomeruli are best described as
involuted glomeruli. We have characterized these involuted glomeruli in detail.
We studied biopsies of 18 children (11 male, 7 female) with frequently relapsing
MCN and evaluated possible explanatory variables. The involuted glomeruli can be
differentiated from the other types of global glomerulosclerosis. Most notable is
the presence of vital podocytes and parietal epithelial cells, which have
retained their staining characteristics, in between the matrix, and the absence
of periglomerular and tubulo-interstitial fibrosis. We observed involuted
glomeruli in 12 out of 18 biopsies; the median percentage of involuted glomeruli
was 6% (range 0-33%). The percentage of involuted glomeruli correlated with age
at renal biopsy and the interval between onset of disease and time of renal
biopsy, but not with gender, age at onset of disease, or prednisone dose.
Multivariate analysis revealed that the interval between onset of disease and
time of renal biopsy was the only independent predictor. In conclusion,
glomerular involution is a special form of global glomerulosclerosis. The absence
of periglomerular and tubulo-interstitial fibrosis suggests a different
pathogenesis. Glomerular involution is a slow process. The clinical data suggest
that involution is related to the duration of the disease process.
PMID- 17035938
TI - Membranous and crescentic glomerulonephritis in a patient with anti-nuclear and
anti-neutrophil cytoplasmic antibodies.
PMID- 17035939
TI - Very low protein diet supplemented with ketoanalogs improves blood pressure
control in chronic kidney disease.
AB - Blood pressure (BP) is hardly controlled in chronic kidney disease (CKD). We
compared the effect of very low protein diet (VLPD) supplemented with ketoanalogs
of essential amino acids (0.35 g/kg/day), low protein diet (LPD, 0.60 g/kg/day),
and free diet (FD) on BP in patients with CKD stages 4 and 5. Vegetable proteins
were higher in VLPD (66%) than in LPD (48%). LPD was prescribed to 110
consecutive patients; after run-in, they were invited to start VLPD. Thirty
subjects accepted; 57 decided to continue LPD; 23 refused either diet (FD group).
At baseline, protein intake (g/kg/day) was 0.79+/-0.09 in VLPD, 0.78+/-0.11 in
LPD, and 1.11+/-0.18 in FD (P<0.0001). After 6 months, protein intake was lower
in VLPD than LPD and FD (0.54+/-0.11, 0.78+/-0.10, and 1.04+/-0.21 g/kg/day,
respectively; P<0.0001). BP diminished only in VLPD, from 143+/-19/84+/-10 to
128+/-16/78+/-7 mm Hg (P<0.0001), despite reduction of antihypertensive drugs
(from 2.6+/-1.1 to 1.8+/-1.2; P<0.001). Urinary urea excretion directly
correlated with urinary sodium excretion, which diminished in VLPD (from 181+/-32
to 131+/-36 mEq/day; P<0.001). At multiple regression analysis (R2=0.270,
P<0.0001), BP results independently related to urinary sodium excretion (P=0.023)
and VLPD prescription (P=0.003), but not to the level of protein intake. Thus, in
moderate to advanced CKD, VLPD has an antihypertensive effect likely due to
reduction of salt intake, type of proteins, and ketoanalogs supplementation,
independent of actual protein intake.
PMID- 17035940
TI - Catch-up growth follows an abnormal pattern in experimental renal insufficiency
and growth hormone treatment normalizes it.
AB - The primary goal of this study was to determine if the ability to undergo catch
up growth following a transient injury is preserved in an experimental model of
moderate chronic renal failure (CRF) and the effect of growth hormone (GH)
administration on such phenomenon. Young rats were subtotally nephrectomized
(days 0 and 4) (Nx). From days 11 to 13, food intake was restricted in subgroups
of Nx and control (C) rats (NxR and CR). After refeeding, subgroups of NxR and CR
rats received GH from days 14 to 20 (NxRGH and CRGH). Rats were killed on days 14
(C, CR, Nx, NxR), 17 and 21 (C, CR, CRGH, Nx, NxR, NxRGH), and 36 (C, CR, Nx,
NxR). Longitudinal growth rate was measured by osseous front advance in the
proximal tibiae. With refeeding, growth rate of CR, NxR, and NXrGH rats became
significantly greater than that of C, indicating catch-up growth. This occurred
later and with lower growth rate in NxR than in CR rats, whereas the
characteristics of catch-up growth in CR and NxRGH animals were similar. Changes
in growth rate were associated with modifications in the morphology and
proliferative activity of growth cartilage. We conclude that catch-up growth
occurs in renal insufficiency but follows a different pattern from that observed
with normal renal function. GH treatment normalizes the pattern of catch-up
growth in CRF. Changes in growth velocity are associated to modifications in the
structure and dynamics of growth cartilage.
PMID- 17035941
TI - IL-1beta induces VEGF, independently of PGE2 induction, mainly through the PI3
K/mTOR pathway in renal mesangial cells.
AB - Vascular endothelial growth factor (VEGF) could play a relevant role in
angiogenesis associated with chronic allograft nephropathy. Interleukin-1beta (IL
1beta) has a key role in inflammatory response. It induces prostaglandin (PG) E2,
which is involved in VEGF release by some normal and tumor cells. In the present
work, we studied the effect of IL-1beta on VEGF release by rat mesangial cells,
the transduction signal, and whether or not PGE2 is involved in this effect. IL
1beta induced a time-dependent formation of VEGF (analyzed by enzyme-linked
immunosorbent assay) and PGE2 (analyzed by enzyme immunoassay). The latter
correlated with microsomal-PGE-synthase (mPGES)-1 expression rather than with
cyclooxygenase (COX)-2 in terms of protein, determined by Western blotting. No
effect of IL-1beta on COX-1, cytosolic PGES, or mPGES-2 expression was observed.
Indomethacin exerted a nonsignificant effect on IL-1beta-induced VEGF, and
exogenously added PGE2 exhibited a nonsignificant stimulatory effect on VEGF
formation. SB 203580, a p38 mitogen-activated protein kinase inhibitor, weakly
inhibited the induction of VEGF by IL-1beta in a concentration-dependent manner,
whereas LY 294002, a phosphoinoside 3-kinase (PI3-K) inhibitor, and rapamycin, a
mammalian target of rapamycin (mTOR) inhibitor, strongly inhibited both IL-1beta-
and tumor necrosis factor-alpha-induced VEGF formation in a concentration
dependent manner. Rapamycin also decreased glomerular VEGF levels in the anti
Thy1.1 model of experimental glomerulonephritis. In conclusion, the PI3-K-mTOR
pathway seems to be essential in cytokine-induced release of VEGF in mesangial
cells.
PMID- 17035942
TI - The urokinase plasminogen activator receptor is crucially involved in host
defense during acute pyelonephritis.
AB - The urokinase plasminogen activator receptor (uPAR) is expressed at the cell
surface of inflammatory cells and plays an important role in neutrophil
migration. To investigate the in vivo role of uPAR during urinary tract
infection, acute pyelonephritis was induced in uPAR-/- and wild-type (WT) mice by
intravesical inoculation with 1 x 10(9) colony-forming units (CFU) of
uropathogenic Escherichia coli. Mice were killed after 24 and 48 h, after which
bacterial outgrowth and cytokine levels in kidney homogenates were determined.
Influx of neutrophils was quantified by myeloperoxidase-enzyme-linked
immunosorbent assay. uPAR-/- kidneys had significantly higher numbers of E. coli
CFU, accompanied by higher levels of interleukin-1beta (IL-1beta), IL-6,
keratinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2),
and tumor necrosis factor-alpha (TNF-alpha). However, the number of infiltrating
neutrophils was similar in uPAR-/- and WT mice at both time points, suggesting
that uPAR-/- neutrophils have a lower ability to eliminate E. coli. To further
investigate this, neutrophil oxidative burst and phagocytosis was measured. The
generation of reactive oxygen species upon stimulation with E. coli was not
diminished in uPAR-/- neutrophils compared with WT. Interestingly, uPAR-/-
neutrophils displayed significantly impaired phagocytosis of E. coli organisms
compared with WT neutrophils. We conclude that uPAR is crucially involved in host
defense through phagocytosis during E. coli induced acute pyelonephritis.
PMID- 17035943
TI - Methotrexate-associated B-cell lymphoma presenting with acute renal failure and
bilateral nephromegaly.
PMID- 17035944
TI - Expression of allograft inflammatory factor-1 in kidneys: A novel molecular
component of podocyte.
AB - Our comprehensive gene expression profiles of the kidneys in an anti-glomerular
basement membrane (GBM) nephritis model using DNA arrays revealed that allograft
inflammatory factor-1 (AIF-1) was one of the highly expressed genes. Here, we
explored the pathological significance of AIF-1 expression in the kidneys. The
expression pattern of AIF-1 mRNA and protein in the kidneys of normal and
diseased rats, such as anti-GBM nephritis and puromycin aminonucleoside
nephrosis, was investigated by in situ hybridization, immunohistochemistry, and
immunoelectron microscopy. Furthermore, the expression of AIF-1 in human kidneys
and urinary sediments was examined. AIF-1 was expressed at both mRNA and protein
levels in podocytes of normal and diseased rats, and in infiltrating cells in
anti-GBM nephritis kidneys. The expression of AIF-1 in podocytes was
constitutive; positive in podocytes of both normal and diseased rats. In humans,
AIF-1 was expressed in podocytes and infiltrating inflammatory cells, similarly.
Moreover, it was detected in urinary podocytes from patients with immunoglobulin
A nephropathy. These data document for the first time that AIF-1, a
constitutively expressed protein in rat and human podocytes, is a novel molecular
component of podocytes, and that the upregulation of AIF-1 in an anti-GBM
nephritis model may mainly be a consequence of its expression in infiltrating
cells.
PMID- 17035946
TI - Lost in publication: Half of all renal practice evidence is published in non
renal journals.
AB - Physicians often scan a select number of journals to keep up to date with
practice evidence for patients with kidney conditions. This raises the question
of where relevant studies are published. We performed a bibliometric analysis
using 195 renal systematic reviews. Each review used a comprehensive method to
identify all primary studies for a focused clinical question relevant to patient
care. We compiled all the primary studies included in these reviews, and
considered where each study was published. Of the 2779 studies, 1351 (49%) were
published in the top 20 journals. Predictably, this list included Transplantation
Proceedings (5.9% of studies), Kidney International (5.3%), American Journal of
Kidney Diseases (4.7%), Nephrology Dialysis Transplantation (4.3%),
Transplantation (4.2%), and Journal of the American Society of Nephrology (2.4%).
Ten non-renal journals were also on this list, including New England Journal of
Medicine (2.4%), Lancet (2.3%), and Diabetes Care (2.2%). The remaining 1428
(51%) studies were published across other 446 journals. When the disciplines of
all journals were considered, 59 were classified as renal or transplant journals
(42% of articles). Other specialties included general and internal medicine
(16%), endocrinology (diabetes) and metabolism (6.5%), surgery (6.2%),
cardiovascular diseases (6.1%), pediatrics (4.3%), and radiology (3.3%). About
half of all renal practice evidence is published in non-renal journals. Browsing
the top journals is important. However, relevant studies are also scattered
across a large range of journals that may not be routinely scanned by busy
physicians, and keeping up with this literature requires other continuing
education strategies.
PMID- 17035945
TI - Cognitive function in Stage 5 chronic kidney disease patients on hemodialysis: no
adverse effects of lanthanum carbonate compared with standard phosphate-binder
therapy.
AB - Patients with Stage 5 chronic kidney disease who have hyperphosphatemia require
treatment with phosphate binders to lower serum phosphorus levels. Existing
binders are effective but may be associated with important safety disadvantages.
Lanthanum carbonate is a phosphate binder with demonstrated efficacy, safety, and
tolerability in clinical trials. Changes in cognitive function were evaluated
over time using the Cognitive Drug Research computerized cognitive assessment
system (Simple Reaction Time, Digit Vigilance Task, Choice Reaction Time, Numeric
Working Memory, and Delayed Picture Recognition) in 360 hemodialysis patients who
were enrolled in a 2-year, multicenter, comparative study of lanthanum carbonate
versus standard therapy. A decline in cognitive function from baseline was
observed in both groups. The deterioration in cognitive function was similar in
both the lanthanum carbonate and standard therapy groups. One parameter - Numeric
Working Memory - showed a statistically significant between-group difference in
favor of lanthanum carbonate (P=0.02). Given the magnitude of the changes,
however, and the differences that were observed at baseline between treatment
groups, the clinical significance of this difference is doubtful. This study
demonstrates that cognitive function deteriorates in hemodialysis patients over a
2-year time period. Use of lanthanum carbonate as a phosphate binder does not
adversely affect cognitive function compared with standard therapy.
PMID- 17035947
TI - BRAVO I: A pilot study of vascular brachytherapy in polytetrafluoroethylene
dialysis access grafts.
AB - Hemodialysis vascular access dysfunction owing to stenosis and thrombosis in
polytetrafluoroethylene dialysis access grafts is a huge clinical problem for
which there are currently no long lasting durable therapies. Vascular
brachytherapy has been used successfully for the prevention of coronary
restenosis following angioplasty and stent placement. The Beta Radiation for
Treatment of Arterial-Venous Graft Outflow I study was a pilot study of vascular
brachytherapy in hemodialysis patients with patent but dysfunctional grafts.
Twenty-five patients were randomized to receive either radiation therapy (a
single dose of 18.4 Gy) or sham radiation, following angioplasty. The primary
efficacy end point of the study was target lesion primary patency at 6 months.
The primary safety end point was a composite of death, emergency surgery on the
graft, venous rupture, or aneurysm formation. Forty-two percent of the radiated
grafts achieved the target lesion primary patency end point at 6 months as
compared to 0% of the control group (P = 0.015), but this did not translate into
an improvement in secondary patency at either 6 or 12 months. Radiation therapy
was found to be safe in the setting of hemodialysis vascular access dysfunction.
Our results suggest that vascular brachytherapy is an intervention that is worthy
of further examination in the setting of non-thrombosed dialysis access grafts.
PMID- 17035948
TI - Analysis of fluid transport pathways and their determinants in peritoneal
dialysis patients with ultrafiltration failure.
AB - Ultrafiltration failure (UFF) is a serious complication of peritoneal dialysis
(PD). The aim of the study was to analyze changes in water transport and their
determinants in UFF patients over the time on PD. Standard peritoneal
permeability analyses of 50 stable PD patients with UFF were analyzed. Fluid
transport through small pores (SPT), free water transport (FWT) at 60 min, their
contributions on total ultrafiltration (SPTC and FWTC), and their determinants
were assessed. Patients were divided in Group I (UFF) treated for less than 24
months, Group II treated 24-60 months, and Group III treated for more than 60
months. Group I (UFF) was compared with Group I (non-UFF) matched for the
duration of PD treatment and age. Transcapillary ultrafiltration (TCUF), SPT,
FWT, and FWTC were significantly lower in Group III when compared to the other
UFF groups. In this group also, negative relationship was present between FWT,
the ultrafiltration coefficient LpA, and osmotic conductance to glucose on one
hand and PD duration on the other. FWT was positively related to osmotic
conductance to glucose in all groups. Group I (UFF) showed significantly higher
solute transport, effective lymphatic absorption rate, lower TCUF, and lower FWT
than Group I (non-UFF). The patterns of UFF in PD patients are dependent on the
duration of treatment.
PMID- 17035949
TI - Long-term effects of spironolactone on proteinuria and kidney function in
patients with chronic kidney disease.
AB - Experimental evidence suggests that aldosterone contributes to progressive kidney
disease. Angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor
antagonists suppress the renin-angiotensin system but they do not effectively
reduce plasma aldosterone. Hence, administration of aldosterone receptor
antagonists may provide additional renal protection. In the present prospective
randomized open-label study, we evaluated the effects of spironolactone (25
mg/day for 1 year) on proteinuria and estimated glomerular filtration rate in 83
patients with chronic kidney disease already treated with angiotensin-converting
enzyme inhibitors and/or angiotensin type 1 receptor antagonists. Eighty-two
patients were treated with angiotensin-converting enzyme inhibitors and/or
angiotensin type 1 receptor antagonists alone and served as controls. After 1
year of therapy, proteinuria decreased from 2.1+/-0.08 to 0.89+/-0.06 g/g
creatinine (P<0.001) in patients treated with spironolactone, but it did not
change in control patients. Baseline aldosterone levels were significantly
correlated with proteinuria (r=0.76, P<0.0001), and predicted the degree of
reduction in proteinuria with spironolactone (r=0.42, P<0.0002). Baseline
estimated glomerular filtration rate was similar in patients treated with
spironolactone and controls (62.4+/-2.4 and 62.2+/-2.1 ml/min/1.73 m(2),
respectively). After 1 month of therapy with spironolactone, estimated glomerular
filtration rate decreased more in patients treated with spironolactone than in
controls. However, by the end of 1 year the monthly rate of decrease in estimated
glomerular filtration rate from baseline was lower in patients treated with
spironolactone than in controls (0.323+/-0.044 vs 0.474+/-0.037 ml/min/1.73 m(2),
P<0.01). Spironolactone caused a significant rise in serum potassium levels (from
4.2+/-0.04 at baseline to 5.0+/-0.05 mEq/l after 12 months of treatment,
P<0.001). In conclusion, this study has shown that spironolactone may reduce
proteinuria and retard renal progression in chronic kidney disease patients.
PMID- 17035950
TI - Ethics of reconstructing Spanish flu: is it wise to resurrect a deadly virus?
PMID- 17035951
TI - Individual-based assessment of population structure and admixture in Austrian,
Croatian and German draught horses.
AB - All over Europe, the number of draught horses has decreased drastically during
the last 50 years. As a prerequisite for efficient management decisions, we
analysed the conservation status in Austrian (Noriker Carinthia - NC, Noriker
Salzburg - NS), Croatian (Croatian Coldblood - C, Posavina horse - P) and German
(Altmaerkisch Coldblood - A, Black Forest horse - BF, Mecklenburg Coldblood - M,
Rhenish German Draught horse - R, Saxon Thuringa Coldblood - ST, Schleswig
Draught horse - Sch, South German Coldblood - SG) draught horses (434) using
multilocus genotypic information from 30 (effectively 27) microsatellite loci.
Populations located in areas with less intensive agricultural production (C, NC,
NS, P and SG) had greater diversity within the population and estimated effective
population size than A, BF, Sch, M, R and ST populations. The PCA plots revealed
that populations form five separate groups. The 'Noriker' group (NC, NS and SG)
and the 'Rhenish' group (A, M, R and ST) were the most distinctive (pairwise
F(ST) values ranged from 0.078 to 0.094). The 'Croatian' group (C and P) was in
the centre, while the BF and Sch populations formed two out-groups. A posterior
Bayesian analysis detected further differentiation, mainly caused by political
and geographical factors. Thus, it was possible to separate the South German
Coldblood from the Austrian Noriker population where no subpopulation structure
was detected. The admixture analysis revealed imprecise classification between C
and P populations. A small but notable separation of R from A, M and ST
populations was detected, while Sch and BF populations remained as out-groups.
The information obtained should aid in making efficient conservation decisions.
PMID- 17035952
TI - A simple method for detection of imprinting effects based on case-parents trios.
AB - Using data from families in which marker genotypes are known for the father, the
mother and the affected offspring, a simple statistic for testing for imprinting
effects is developed. The statistic considers whether the expected number of
families in which the father carries more copies of a particular marker allele
than the mother is equal to the expected number of families in which the mother
carries more copies of the allele than the father. The proposed parent-of-origin
effects test statistic (POET) is shown to be normally distributed and can be
employed to test for imprinting in situations where the marker locus need not be
a disease susceptibility locus and where the female and male recombination
fractions are sex-specific. A simulation study is conducted to characterize the
power of the POET and other properties, and its results show that it is
appropriate to employ the POET.
PMID- 17035953
TI - Genetic interactions between the parasitoid wasp Leptopilina boulardi and its
Drosophila hosts.
AB - Coevolutionary arms races between hosts and parasites would not occur without
genetic variation for traits involved in the outcome of parasitism. Genetic
variations in resistance and virulence have only rarely been described in
pairwise host-parasitoid interactions and have never been analysed in multi
species interactions, in contrast to well-characterized plant-pathogen
interactions. This paper reports genetic variation in resistance of Drosophila
yakuba to the parasitoid wasp Leptopilina boulardi. The genetic basis and
geographic distribution of resistance is analysed. On the basis of these and
previous findings, we demonstrate that there are different resistance patterns to
the parasitoid species L. boulardi in D. melanogaster and D. yakuba, as well as
different specificity levels in the parasitoid species, suggesting complex
ecological interactions in the field. This first description of resistance
virulence genetic interactions between a parasitoid and its two host species
provides empirical data showing that multi-species interactions may greatly
influence coevolutionary processes.
PMID- 17035954
TI - Cardinium symbionts cause cytoplasmic incompatibility in spider mites.
AB - Intracellular symbiotic bacteria belonging to the Cytophaga-Flavobacterium
Bacteroides lineage have recently been described and are widely distributed in
arthropod species. The newly discovered bacteria, named Cardinium sp, cause the
expression of various reproductive alterations in their arthropod hosts,
including cytoplasmic incompatibility (CI), induction of parthenogenesis and
feminization of genetic males. We detected 16S ribosomal DNA sequences similar to
those of Cardinium from seven populations of five spider mite species, suggesting
a broad distribution of infection of Cardinium in spider mites. To clarify the
effect of Cardinium on the reproductive traits of the infected spider mites,
infected mites were crossed with uninfected mites for each population. In one of
the populations, Eotetranychus suginamensis, CI was induced when infected males
were crossed with uninfected females. The other six populations of four species
showed no reproductive abnormalities in the F(1) generation, but the possibility
of CI effects in the F(2) generation remains to be tested. One species of spider
mite, Tetranychus pueraricola, harbored both Cardinium and Wolbachia, but these
symbionts seemed to have no effect on the reproduction of the host, even when the
host was infected independently with each symbiont.
PMID- 17035955
TI - Evaluating the environmental impact of various dietary patterns combined with
different food production systems.
AB - OBJECTIVE: Recent studies support the hypothesis that plant-based diets are
environmentally better than meat-based diets. This study aims to further explore
this topic and to compare different environmental impacts resulting from
different dietary patterns (omnivorous, vegetarian, vegan) and methods of
production (conventional farming and organic agriculture). DESIGN: Three weekly
balanced diets, equivalent to one another for energetic and nutrient content,
have been planned: an omnivorous one, a vegetarian one and a vegan one. For each
one, the Life Cycle Assessment (LCA) method has been applied in order to
calculate the environmental impact, expressed in 'points'. INTERVENTIONS: The
software we selected to carry out the Inventory Analysis and the Impact
Assessment is SimaPro5. The Assessment phase has been conducted using
Ecoindicator 99, a damage-oriented method, which analyses the impact according to
three large damage categories, each of them subsuming various impact categories.
PMID- 17035958
TI - Forgotten plights.
PMID- 17035959
TI - A global folly.
PMID- 17035960
TI - Ambassador for Earth.
PMID- 17035962
TI - The fizzle heard around the world.
PMID- 17035963
TI - Protests mount against Libyan trial.
PMID- 17035964
TI - Intelligent design gets political.
PMID- 17035965
TI - Nobel prize blurs boundaries.
PMID- 17035966
TI - Hard-hitting endeavour captures Ig Nobel.
PMID- 17035970
TI - Hell on no wheels.
PMID- 17035971
TI - Oceanography: the real sea change.
PMID- 17035972
TI - AIDS in Africa: a question of trust.
PMID- 17035973
TI - Depression: comfortably numb.
PMID- 17035975
TI - Chimp comparisons won't explain human evolution.
PMID- 17035976
TI - Consistency tests establish empirical generalizations.
PMID- 17035977
TI - Videos have starring role to play in protocol sharing.
PMID- 17035978
TI - Biochemistry has outgrown its traditional boundaries.
PMID- 17035984
TI - Particle physics: did the Big Bang boil?
PMID- 17035985
TI - Evolutionary biology: fly eyes get the whole picture.
PMID- 17035987
TI - Physical chemistry: seeds of phase change.
PMID- 17035988
TI - Developmental biology: a change of heart.
PMID- 17035989
TI - Neuroscience: controlled capillaries.
PMID- 17035990
TI - Earth sciences: ups and downs of ancient oxygen.
PMID- 17035991
TI - Ecology: moving to the ideal free home.
PMID- 17035992
TI - Cell biology: mitochondria shape up.
PMID- 17035994
TI - An accessory chromophore in red vision.
AB - In the absence of a red-sensitive visual pigment, some deep-sea fish use a
chlorophyll derivative in their green-sensitive rod cells in order to see deep
red light. Here we show that living rods extracted from a salamander can also
accumulate an exogenous chlorophyll derivative, chlorin e6, that renders them as
sensitive to red light as they are to green. This vision enhancement by an
unbleachable chlorophyll derivative might therefore be a general phenomenon in
vertebrate photoreception.
PMID- 17035995
TI - Phosphoinositides in cell regulation and membrane dynamics.
AB - Inositol phospholipids have long been known to have an important regulatory role
in cell physiology. The repertoire of cellular processes known to be directly or
indirectly controlled by this class of lipids has now dramatically expanded.
Through interactions mediated by their headgroups, which can be reversibly
phosphorylated to generate seven species, phosphoinositides play a fundamental
part in controlling membrane-cytosol interfaces. These lipids mediate acute
responses, but also act as constitutive signals that help define organelle
identity. Their functions, besides classical signal transduction at the cell
surface, include regulation of membrane traffic, the cytoskeleton, nuclear events
and the permeability and transport functions of membranes.
PMID- 17035996
TI - Role of Bax and Bak in mitochondrial morphogenesis.
AB - Bcl-2 family proteins are potent regulators of programmed cell death. Although
their intracellular localization to mitochondria and the endoplasmic reticulum
has focused research on these organelles, how they function remains unknown. Two
members of the Bcl-2 family, Bax and Bak, change intracellular location early in
the promotion of apoptosis to concentrate in focal clusters at sites of
mitochondrial division. Here we report that in healthy cells Bax or Bak is
required for normal fusion of mitochondria into elongated tubules. Bax seems to
induce mitochondrial fusion by activating assembly of the large GTPase Mfn2 and
changing its submitochondrial distribution and membrane mobility-properties that
correlate with different GTP-bound states of Mfn2. Our results show that Bax and
Bak regulate mitochondrial dynamics in healthy cells and indicate that Bcl-2
family members may also regulate apoptosis through organelle morphogenesis
machineries.
PMID- 17035997
TI - The sequestration of ethane on Titan in smog particles.
AB - Saturn's largest satellite, Titan, has a dense atmosphere of nitrogen with a few
per cent of methane. At visible wavelengths its surface is hidden by dense orange
brown smog, which is produced in the stratosphere by photochemical reactions
following the dissociation of methane by solar ultraviolet light. The most
abundant of the products of these reactions is ethane, and enough of it should
have been generated over the life of the Solar System to form a satellite-wide
ocean one kilometre deep. Radar observations have found specular reflections in
75 per cent of the surface spots observed, but optical searches for a sun-glint
off an ocean have been negative. Here I explain the mysterious absence or rarity
of liquid ethane: it condenses onto the smog particles, instead of into liquid
drops, at the cold temperatures in Titan's atmosphere. This dusty combination of
smog and ethane, forming deposits several kilometres thick on the surface,
including the observed dunes and dark areas, could be named 'smust'. This
satellite-wide deposit replaces the ocean long thought to be an important feature
of Titan.
PMID- 17035998
TI - Observation of strong coupling between one atom and a monolithic microresonator.
AB - Over the past decade, strong interactions of light and matter at the single
photon level have enabled a wide set of scientific advances in quantum optics and
quantum information science. This work has been performed principally within the
setting of cavity quantum electrodynamics with diverse physical systems,
including single atoms in Fabry-Perot resonators, quantum dots coupled to
micropillars and photonic bandgap cavities and Cooper pairs interacting with
superconducting resonators. Experiments with single, localized atoms have been at
the forefront of these advances with the use of optical resonators in high
finesse Fabry-Perot configurations. As a result of the extreme technical
challenges involved in further improving the multilayer dielectric mirror
coatings of these resonators and in scaling to large numbers of devices, there
has been increased interest in the development of alternative microcavity
systems. Here we show strong coupling between individual caesium atoms and the
fields of a high-quality toroidal microresonator. From observations of transit
events for single atoms falling through the resonator's evanescent field, we
determine the coherent coupling rate for interactions near the surface of the
resonator. We develop a theoretical model to quantify our observations,
demonstrating that strong coupling is achieved, with the rate of coherent
coupling exceeding the dissipative rates of the atom and the cavity. Our work
opens the way for investigations of optical processes with single atoms and
photons in lithographically fabricated microresonators. Applications include the
implementation of quantum networks, scalable quantum logic with photons, and
quantum information processing on atom chips.
PMID- 17035999
TI - The order of the quantum chromodynamics transition predicted by the standard
model of particle physics.
AB - Quantum chromodynamics (QCD) is the theory of the strong interaction, explaining
(for example) the binding of three almost massless quarks into a much heavier
proton or neutron--and thus most of the mass of the visible Universe. The
standard model of particle physics predicts a QCD-related transition that is
relevant for the evolution of the early Universe. At low temperatures, the
dominant degrees of freedom are colourless bound states of hadrons (such as
protons and pions). However, QCD is asymptotically free, meaning that at high
energies or temperatures the interaction gets weaker and weaker, causing hadrons
to break up. This behaviour underlies the predicted cosmological transition
between the low-temperature hadronic phase and a high-temperature quark-gluon
plasma phase (for simplicity, we use the word 'phase' to characterize regions
with different dominant degrees of freedom). Despite enormous theoretical effort,
the nature of this finite-temperature QCD transition (that is, first-order,
second-order or analytic crossover) remains ambiguous. Here we determine the
nature of the QCD transition using computationally demanding lattice calculations
for physical quark masses. Susceptibilities are extrapolated to vanishing lattice
spacing for three physical volumes, the smallest and largest of which differ by a
factor of five. This ensures that a true transition should result in a dramatic
increase of the susceptibilities. No such behaviour is observed: our finite-size
scaling analysis shows that the finite-temperature QCD transition in the hot
early Universe was not a real phase transition, but an analytic crossover
(involving a rapid change, as opposed to a jump, as the temperature varied). As
such, it will be difficult to find experimental evidence of this transition from
astronomical observations.
PMID- 17036000
TI - Origin of the dielectric dead layer in nanoscale capacitors.
AB - Capacitors are a mainstay of electronic integrated circuits and devices, where
they perform essential functions such as storing electrical charge, and blocking
direct current while allowing alternating currents to propagate. Because they are
often the largest components in circuits, extensive efforts are directed at
reducing their size through the use of high-permittivity insulators such as
perovskite-structure SrTiO3 (refs 1, 2), which should provide more capacitance
per unit area of device. Unfortunately, most experiments on thin-film SrTiO3
capacitors have yielded capacitance values that are orders of magnitude smaller
than expected. The microscopic origin of this reduced capacitance, which is often
discussed in terms of a low-permittivity interfacial 'dead layer', is not well
understood. Whether such a dead layer exists at all, and if so, whether it is an
intrinsic property of an ideal metal-insulator interface or a result of
processing issues such as defects and strains, are controversial questions. Here
we present fully ab initio calculations of the dielectric properties of realistic
SrRuO3/SrTiO3/SrRuO3 nanocapacitors, and show that the observed dramatic
capacitance reduction is indeed an intrinsic effect. We demonstrate the existence
of a dielectric dead layer by calculating the dielectric profile across the
interface and analyse its origin by extracting the ionic and electronic
contributions to the electrostatic screening. We establish a correspondence
between the dead layer and the hardening of the collective SrTiO3 zone-centre
polar modes, and determine the influence of the electrode by repeating our
calculations for Pt/SrTiO3/Pt capacitors. Our results provide practical
guidelines for minimizing the deleterious effects of the dielectric dead layer in
nanoscale devices.
PMID- 17036001
TI - Bistability of atmospheric oxygen and the Great Oxidation.
AB - The history of the Earth has been characterized by a series of major transitions
separated by long periods of relative stability. The largest chemical transition
was the 'Great Oxidation', approximately 2.4 billion years ago, when atmospheric
oxygen concentrations rose from less than 10(-5) of the present atmospheric level
(PAL) to more than 0.01 PAL, and possibly to more than 0.1 PAL. This transition
took place long after oxygenic photosynthesis is thought to have evolved, but the
causes of this delay and of the Great Oxidation itself remain uncertain. Here we
show that the origin of oxygenic photosynthesis gave rise to two simultaneously
stable steady states for atmospheric oxygen. The existence of a low-oxygen (less
than 10(-5) PAL) steady state explains how a reducing atmosphere persisted for at
least 300 million years after the onset of oxygenic photosynthesis. The Great
Oxidation can be understood as a switch to the high-oxygen (more than 5 x 10(-3)
PAL) steady state. The bistability arises because ultraviolet shielding of the
troposphere by ozone becomes effective once oxygen levels exceed 10(-5) PAL,
causing a nonlinear increase in the lifetime of atmospheric oxygen. Our results
indicate that the existence of oxygenic photosynthesis is not a sufficient
condition for either an oxygen-rich atmosphere or the presence of an ozone layer,
which has implications for detecting life on other planets using atmospheric
analysis and for the evolution of multicellular life.
PMID- 17036002
TI - Long-period astronomical forcing of mammal turnover.
AB - Mammals are among the fastest-radiating groups, being characterized by a mean
species lifespan of the order of 2.5 million years (Myr). The basis for this
characteristic timescale of origination, extinction and turnover is not well
understood. Various studies have invoked climate change to explain mammalian
species turnover, but other studies have either challenged or only partly
confirmed the climate-turnover hypothesis. Here we use an exceptionally long
(24.5-2.5 Myr ago), dense, and well-dated terrestrial record of rodent lineages
from central Spain, and show the existence of turnover cycles with periods of 2.4
2.5 and 1.0 Myr. We link these cycles to low-frequency modulations of
Milankovitch oscillations, and show that pulses of turnover occur at minima of
the 2.37-Myr eccentricity cycle and nodes of the 1.2-Myr obliquity cycle. Because
obliquity nodes and eccentricity minima are associated with ice sheet expansion
and cooling and affect regional precipitation, we infer that long-period
astronomical climate forcing is a major determinant of species turnover in small
mammals and probably other groups as well.
PMID- 17036003
TI - Low-coverage vaccination strategies for the conservation of endangered species.
AB - The conventional objective of vaccination programmes is to eliminate infection by
reducing the reproduction number of an infectious agent to less than one, which
generally requires vaccination of the majority of individuals. In populations of
endangered wildlife, the intervention required to deliver such coverage can be
undesirable and impractical; however, endangered populations are increasingly
threatened by outbreaks of infectious disease for which effective vaccines exist.
As an alternative, wildlife epidemiologists could adopt a vaccination strategy
that protects a population from the consequences of only the largest outbreaks of
disease. Here we provide a successful example of this strategy in the Ethiopian
wolf, the world's rarest canid, which persists in small subpopulations threatened
by repeated outbreaks of rabies introduced by domestic dogs. On the basis of data
from past outbreaks, we propose an approach that controls the spread of disease
through habitat corridors between subpopulations and that requires only low
vaccination coverage. This approach reduces the extent of rabies outbreaks and
should significantly enhance the long-term persistence of the population. Our
study shows that vaccination used to enhance metapopulation persistence through
elimination of the largest outbreaks of disease requires lower coverage than the
conventional objective of reducing the reproduction number of an infectious agent
to less than one.
PMID- 17036004
TI - Transforming the architecture of compound eyes.
AB - Eyes differ markedly in the animal kingdom, and are an extreme example of the
evolution of multiple anatomical solutions to light detection and image
formation. A salient feature of all photoreceptor cells is the presence of a
specialized compartment (disc outer segments in vertebrates, and microvillar
rhabdomeres in insects), whose primary role is to accommodate the millions of
light receptor molecules required for efficient photon collection. In insects,
compound eyes can have very different inner architectures. Fruitflies and
houseflies have an open rhabdom system, in which the seven rhabdomeres of each
ommatidium are separated from each other and function as independent light
guides. In contrast, bees and various mosquitoes and beetle species have a closed
system, in which rhabdomeres within each ommatidium are fused to each other, thus
sharing the same visual axis. To understand the transition between open and
closed rhabdom systems, we isolated and characterized the role of Drosophila
genes involved in rhabdomere assembly. Here we show that Spacemaker, a secreted
protein expressed only in the eyes of insects with open rhabdom systems, acts
together with Prominin and the cell adhesion molecule Chaoptin to choreograph the
partitioning of rhabdomeres into an open system. Furthermore, the complete loss
of spacemaker (spam) converts an open rhabdom system to a closed one, whereas its
targeted expression to photoreceptors of a closed system markedly reorganizes the
architecture of the compound eyes to resemble an open system. Our results provide
a molecular atlas for the construction of microvillar assemblies and illustrate
the critical effect of differences in a single structural protein in
morphogenesis.
PMID- 17036005
TI - Bidirectional control of CNS capillary diameter by pericytes.
AB - Neural activity increases local blood flow in the central nervous system (CNS),
which is the basis of BOLD (blood oxygen level dependent) and PET (positron
emission tomography) functional imaging techniques. Blood flow is assumed to be
regulated by precapillary arterioles, because capillaries lack smooth muscle.
However, most (65%) noradrenergic innervation of CNS blood vessels terminates
near capillaries rather than arterioles, and in muscle and brain a dilatory
signal propagates from vessels near metabolically active cells to precapillary
arterioles, suggesting that blood flow control is initiated in capillaries.
Pericytes, which are apposed to CNS capillaries and contain contractile proteins,
could initiate such signalling. Here we show that pericytes can control capillary
diameter in whole retina and cerebellar slices. Electrical stimulation of retinal
pericytes evoked a localized capillary constriction, which propagated at
approximately 2 microm s(-1) to constrict distant pericytes. Superfused ATP in
retina or noradrenaline in cerebellum resulted in constriction of capillaries by
pericytes, and glutamate reversed the constriction produced by noradrenaline.
Electrical stimulation or puffing GABA (gamma-amino butyric acid) receptor
blockers in the inner retina also evoked pericyte constriction. In simulated
ischaemia, some pericytes constricted capillaries. Pericytes are probably
modulators of blood flow in response to changes in neural activity, which may
contribute to functional imaging signals and to CNS vascular disease.
PMID- 17036006
TI - Fast neurotransmitter release triggered by Ca influx through AMPA-type glutamate
receptors.
AB - Feedback inhibition at reciprocal synapses between A17 amacrine cells and rod
bipolar cells (RBCs) shapes light-evoked responses in the retina. Glutamate
mediated excitation of A17 cells elicits GABA (gamma-aminobutyric acid)-mediated
inhibitory feedback onto RBCs, but the mechanisms that underlie GABA release from
the dendrites of A17 cells are unknown. If, as observed at all other synapses
studied, voltage-gated calcium channels (VGCCs) couple membrane depolarization to
neurotransmitter release, feedforward excitatory postsynaptic potentials could
spread through A17 dendrites to elicit 'surround' feedback inhibitory
transmission at neighbouring synapses. Here we show, however, that GABA release
from A17 cells in the rat retina does not depend on VGCCs or membrane
depolarization. Instead, calcium-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4
isoxazole propionic acid) receptors (AMPARs), activated by glutamate released
from RBCs, provide the calcium influx necessary to trigger GABA release from A17
cells. The AMPAR-mediated calcium signal is amplified by calcium-induced calcium
release (CICR) from intracellular calcium stores. These results describe a fast
synapse that operates independently of VGCCs and membrane depolarization and
reveal a previously unknown form of feedback inhibition within a neural circuit.
PMID- 17036029
TI - Erythromycin and feeding intolerance in premature infants: a randomized trial.
AB - OBJECTIVES: To evaluate the effectiveness of low-dose oral erythromycin to treat
feeding intolerance in preterm infants. DESIGN: This study was a prospective,
double-blind, randomized, placebo-controlled trial on 60 premature infants
suffering from feeding intolerance. Thirty infants were given oral erythromycin 1
mg/kg every 8 h and 30 infants were given placebo (normal saline). Randomization
was stratified on enrollment according to gestational age whether >32 weeks or
32 weeks, the erythromycin group achieved full enteral feeding
earlier than placebo group (10.5+/-4.1 vs 16.3+/-5.7 days, respectively; P=0.01)
had fewer episodes of gastric residuals (P<0.05) and shorter duration of
parenteral nutrition (PN) (P<0.05). On the other hand, in infants with
gestational age 32 weeks gestation. A similar effect on
younger preterm infants was not demonstrable.
PMID- 17036007
TI - Identification of nesfatin-1 as a satiety molecule in the hypothalamus.
AB - The brain hypothalamus contains certain secreted molecules that are important in
regulating feeding behaviour. Here we show that nesfatin, corresponding to
NEFA/nucleobindin2 (NUCB2), a secreted protein of unknown function, is expressed
in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular
(i.c.v.) injection of NUCB2 reduces feeding. Rat cerebrospinal fluid contains
nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is
decreased in the hypothalamic paraventricular nucleus under starved conditions.
I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner,
whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In
contrast, i.c.v. injection of other possible fragments processed from NUCB2 does
not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce
feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight,
whereas rats gain body weight after chronic i.c.v. injection of antisense
morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1-induced
anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti
nesfatin-1 antibody does not block leptin-induced anorexia. In contrast, central
injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression
in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an
antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety
molecule that is associated with melanocortin signalling in the hypothalamus.
PMID- 17036030
TI - Gastroschisis in the United States 1988-2003: analysis and risk categorization of
4344 patients.
AB - OBJECTIVE: Gastroschisis is a rare congenital abdominal wall defect through which
intraabdominal organs herniate and it requires surgical management soon after
birth. The objectives of this study were to profile patient characteristics of
this anomaly utilizing data from two large national databases and to validate
previous risk stratification categories of infants born with this condition.
METHODS: An analysis was performed using 13 years of the National Inpatient
Sample database (1988-1996, 1998, 1999, 2001, 2002) and 3 years of the Kids'
Inpatient Database (1997, 2000, 2003). These combined databases contain
information from nearly 93 million discharges in the United States. Infants with
gastroschisis were identified by International Classification of Disease-9
procedure code 54.71 (repair of gastroschisis) and an age at admission of <8
days. Variables of gender, race, geographic region, co-existing diagnoses, length
of stay, hospital charges adjusted to 2005 dollars, complications and inpatient
mortality were collected from the databases. Infants were divided into simple and
complex categories based on the absence or presence of intestinal atresia,
stenosis, perforation, necrosis or volvulus. Comparisons between groups were
performed using Pearson's chi (2) for categorical outcomes and the Kruskal-Wallis
test for non-normally distributed continuous variables. RESULTS: A total of 4344
infants with gastroschisis were identified. These were comprised of 44.0% female
infants (n=1910), 46.4% male infants (n=2017) whereas 9.6% were not reported
(n=415). Racial analysis showed the largest subset being white in 40.9% of
infants (n=1775) with Hispanic infants being the next highest group reported at
17.2% (n=745). Co-existing intestinal anomalies were the most common, affecting
9.9% (n=429) infants, whereas certain cardiac (6.8%, n=294) and pulmonary (1.7%,
n=72) conditions were also identified. Simple gastroschisis represented 89.1%
(n=3870) of the group whereas 10.9% (n=474) were complex in nature. Simple and
complex patients differed in median length of stay (28 vs 67 days, P<0.01),
inpatient mortality (2.9 vs 8.7%, P<0.01) and median inflation-adjusted hospital
charges (90,788 dollars vs 197,871 dollars, P<0.01). CONCLUSIONS: These data
represent a national analysis of the largest group of infants with gastroschisis
to date which further aids the characterization and understanding of this serious
congenital condition.
PMID- 17036031
TI - Outcomes associated with cesarean section versus vaginal breech delivery at a
university hospital.
AB - OBJECTIVE: To determine whether vaginal breech delivery is associated with
increased morbidity in term breech singletons using strict selection criteria.
This study encompasses our previous studies (in 1987 and 1995) and extends our
experience to 21 years. STUDY DESIGN: Retrospective cohort study from 1980 to
2001 including term, non-anomalous singleton breech deliveries selected by strict
criteria. Univariable and multivariable analyses were performed for neonatal and
maternal outcomes. RESULTS: Five hundred and eleven women underwent cesarean
section and 214 a trial of labor. We found greater overall maternal morbidity in
the cesarean section group (odds ratio (OR) 1.89, 95% confidence interval
(CI)=1.34-2.65). In the vaginal delivery group, neonates were more likely to have
had >1 day of mechanical ventilation (OR 10.0, 95% CI=1.56-63.9). No maternal
deaths occurred and no neonatal deaths or seizures occurred. CONCLUSION: Given
our findings, offering a trial of vaginal breech delivery to well-counseled
strictly selected patients remains an appropriate option.
PMID- 17036032
TI - Avoiding hyperoxia in infants < or = 1250 g is associated with improved short-
and long-term outcomes.
AB - OBJECTIVE: To determine the rate and severity of short- and long-term morbidity
in very low birth weight infants treated before and after the implementation of a
change in clinical practice designed to avoid hyperoxia. METHODS: Analysis of a
prospectively collected database of all infants < or = 1250 g admitted to two
Emory University NICU's from January 2000 to December 2004. A change in practice
was instituted in January 2003 with the objective of avoiding hyperoxia in
preterm infants with target O2 saturation (SpO2) at 93 to 85% (Period II). Before
the change in practice, SpO2 high alarms were set at 100% and low alarms at 92%
(Period I). Statistical analysis included bivariate analyses and multivariate
logistic regression comparing outcomes between the two periods. RESULTS: From
January 2000 to December 2004, 502 infants met enrollment criteria and 202 (40%)
were born in period II, after change in SpO2 targets. Birth weight, gestational
age and survival were similar between both periods. The rates for any retinopathy
of prematurity, supplemental oxygen at 36 weeks post-conceptional age and the use
of steroids for chronic lung disease were significantly lower in the infants born
in Period II. There was no difference in the rates of necrotizing enterocolitis,
intraventricular hemorrhage and periventricular leukomalacia. At 18 months
corrected age (CA), the infants treated during Period II had a higher Mental
Developmental Index (MDI) scores (80.2 +/- 18.3 vs 89.2 +/- 18.5; P 0.02) and
similar Psychomotor Developmental Index (PDI) scores (83.9 +/- 18.6 vs 89.4 +/-
17.2; P 0.08) than those treated during Period I. The proportion of infants with
an MDI or a PDI less than 70 was similar between the periods. CONCLUSIONS: The
change in practice to avoid hyperoxia is associated with a significant decrease
in neonatal morbidity and does not have a detrimental effect on developmental
outcomes at 18 months CA.
PMID- 17036033
TI - Serum creatinine in very low birth weight infants during their first days of
life.
AB - OBJECTIVES: Little is known about the relationship between gestational age (GA)
or birth weight (BW) and serum creatinine (SCr) in very low birth weight (VLBW)
infants. We sought to study postnatal SCr changes and determine if there is a
correlation between GA or BW and SCr in VLBW infants, during their first days of
life. STUDY DESIGN: Medical records of all VLBW infants, who were admitted to our
neonatal intensive care unit (NICU) between 1 May 1998 and 1 May 2001, were
reviewed. Medical records were reviewed for: BW, GA, gender, race, APGAR scores,
mechanical ventilation, use of medications, fluid intake, urinary output, protein
intake, blood urea nitrogen (BUN) and SCr during the first days of life. Patients
with anuria/oliguria, major congenital anomalies, low APGAR scores at 5 min, on
high ventilator settings (on the oscillator), hemodynamically unstable (on
pressors, inotropes) and on indomethacin and diuretics were excluded. RESULTS: In
total, 138 infants met our inclusion criteria. SCr was found to decrease
postnatally, reaching a plateau on day 5 of life in all VLBW infants (repeated
measure analysis of variance; P=0.004); however, there was a delay in the
decrease of SCr in the subgroup of infants <29 weeks GA, and <1000 g BW. SCr (on
day 5 of life) was also found to decrease with increasing GA and BW (Pearson
correlation coefficient: -0.206 (P=0.05) and -0.236 (P=0.05) respectively).
CONCLUSION: In VLBW infants SCr decreases significantly during the first days of
life; however, in infants younger than 29 weeks GA or smaller than 1000 g BW
there is a delay in the decrease of their SCr that extends beyond the first days
of life. We also conclude that during the first days of life, and in VLBW infants
SCr decreases with advancing GA and BW.
PMID- 17036034
TI - Low blood neutrophil concentrations among extremely low birth weight neonates:
data from a multihospital health-care system.
AB - OBJECTIVE: A blood neutrophil concentration < 1000/microl has been reported to
occur in about 8% of neonatal intensive care unit (NICU) patients, at some time
during their hospital stay. However, the incidence of this finding among
extremely low birth weight (ELBW) neonates (< 1000 g birth weight) is not known.
Using data from four NICU's in one health-care system, we sought to estimate the
incidence, timing, causes, severity and duration of neutrophil counts <
1000/microl among ELBW neonates. We also tabulated the treatments used for this
condition and associations with mortality. METHODS: We performed an historic
cohort analysis of all ELBW neonates born during the 36-month period, 1 July 2002
to 30 June 2005, cared for in the four Intermountain Healthcare level III NICU's.
RESULTS: Three hundred and thirty-eight ELBW neonates were the subjects of the
analysis. Complete blood cell counts (CBCs) were obtained in all (range, 1 to 123
CBCs/patient). Thirty-eight percent (128/338) had one or more neutrophil counts <
1000/microl. In 57% the low neutrophil count persisted for < 24 h; in 43% it
persisted for 1 to 7.5 days. Most of the cases (74%) were detected during the
first 3 days of life. Twenty-two percent of cases were not detected until after
the first week. Low neutrophil counts were more common among the smallest
patients, with a 63% incidence in those < or = 500 g, 44% in those 501 to 600 g
and 34% in those 801 to 999 g. When low neutrophil counts were recognized during
the first 3 days of life, the patients were typically either small for
gestational age (SGA; weight < 10th percentile for gestational age) or born after
pregnancy-induced hypertension (PIH) (68%), or had early-onset bacterial
infection (6%). When recognized after the first 3 days, the patients typically
had necrotizing enterocolitis (31%) or a nosocomial bacterial infection (19%).
Alloimmune mechanisms were not tested for in any of the cases. No cause for the
low counts was identified among 35% of the neutropenic patients. Intravenous
immunoglobulins was administered to 28% of cases, and 100% of these were given
according to our written guidelines. Recombinant granulocyte-colony stimulating
factor was administered to 13% of cases, and 69% of these were given according to
guidelines. Neither the presence of low neutrophil counts nor the severity
(lowest recorded count) correlated with mortality rate, except in proven early
onset sepsis. CONCLUSIONS: We observed low neutrophil counts among ELBW neonates
at a rate five times that reported in the general NICU population. Most cases
were present in the first days of life and occurred in SGA neonates or those with
PIH. In over 1/3, no cause was discovered. We maintain that more consistency is
needed in evaluating and treating neutropenia among ELBW neonates.
PMID- 17036035
TI - Neonatal illicit drug screening practices in Iowa: the impact of utilization of a
structured screening protocol.
AB - OBJECTIVE: The purpose of the study was to determine the neonatal illicit drug
screening practices of Iowa birthing hospitals. STUDY DESIGN: Cross-sectional
survey design was implemented. The impact of structured screening protocols on
the numbers of neonates screened and positive testing in 2004 was reviewed.
RESULTS: Of 81 birthing hospitals, 53 (65%) participated in the study. Screening
and positive test rates were higher in hospitals utilizing a structured screening
protocol compared to those not utilizing one (10.9 versus 2.1% and 0.9 versus
0.2%, respectively, P < 0.0001). Hospitals with higher population, numbers of
outpatients, inpatients, deliveries, and availability of drug abuse treatment
services utilized a structured screening protocol more often. CONCLUSION:
Utilization of a structured screening protocol increases the number of neonates
screened for illicit drugs and positive testing rate regardless of urbanization.
Regional standardization of structured screening protocols may improve the
recognition of perinatal illicit drug exposure and provision of treatment
services.
PMID- 17036037
TI - Guido Fanconi (1892-1979): a jack of all trades.
AB - In 1927 the Swiss paediatrician Guido Fanconi described a family in which three
boys had physical birth defects and died of a condition that resembled pernicious
anaemia. In the 1960, inspired by Fanconi's theoretical considerations, it was
shown that the disorder is based on an underlying chromosomal instability and is
associated with a predisposition to bone marrow failure and cancer. As the 80th
anniversary of the first description of Fanconi anaemia approaches, we were
motivated to pay tribute to Guido Fanconi as an outstanding figure in European
medicine and to honour his contribution to cancer research.
PMID- 17036038
TI - Selecting targets for cancer prevention: where do we go from here?
AB - Given the lack of progress in curing metastatic epithelial cancers, there is
intense interest in, and a sound scientific rationale for, pursuing strategies to
prevent cancer. However, although several clinical trials have shown efficacy in
cancer prevention, few have resulted in changes to medical practice, and some
trials have even shown harm. Recent experiences with serious side effects
identified in cancer prevention trials underscore the need to re-evaluate our
approach to clinical chemopreventive drug development, and to establish a
framework for agent selection for future trials.
PMID- 17036039
TI - Breast cancer treatment and ovarian failure: risk factors and emerging genetic
determinants.
AB - Most premenopausal women diagnosed with primary breast cancer receive adjuvant
chemotherapy, and many experience chemotherapy-induced ovarian failure (CIOF).
CIOF is associated with menopausal symptoms, fertility concerns and long-term
implications including bone loss. Ironically, CIOF might confer a disease
specific benefit to women whose breast cancers express hormone receptors. Risk
factors of CIOF include the woman's age at the time of therapy, and the type,
dose and schedule of chemotherapy. Because inherited genetic factors have an
important role in determining who will experience CIOF, genetic testing has the
potential to provide optimal counselling about risks and possible interventions.
PMID- 17036040
TI - The multifaceted circulating endothelial cell in cancer: towards marker and
target identification.
AB - Increases in the number of circulating endothelial cells (CECs) and progenitors
(CEPs) have been reported in various pathological conditions including cancer.
Preclinical studies have shown that CEC and CEP kinetics correlate well with
several standard laboratory angiogenesis assays, which cannot be used in humans.
At the clinical level, evidence is emerging that CEC kinetics and viability might
correlate with clinical outcomes in cancer patients who undergo anti-angiogenic
treatment. Therefore, CEC and CEP measurement has potential as a surrogate marker
for monitoring anti-angiogenic treatment and drug activity, and could help to
determine the optimal biological dose of anti-angiogenic drugs, which are being
used with increasing frequency in medical oncology.
PMID- 17036041
TI - Integration of EGFR inhibitors with radiochemotherapy.
AB - Laboratory studies that led to the development of epidermal growth factor
receptor (EGFR) inhibitors indicated that such inhibitors would be effective when
given to patients with tumours that are driven by activated EGFR. However,
initial clinical studies have shown modest responses to EGFR inhibitors when used
alone, and it has not yet been possible to clearly identify which tumours will
respond to this therapy. As a result, EGFR inhibitors are now used in combination
with radiation therapy, chemotherapy and, more recently, with concurrent
radiochemotherapy. In general, these clinical trials have been designed without
much preclinical data. What do we need to know to make these combinations
successful in the clinic?
PMID- 17036042
TI - Use of antihypertensive and lipid-lowering drugs: the management of
cardiovascular risk in clinical practice.
AB - The objective of the study was to analyse the treatment of high blood pressure
(BP) and hypercholesterolaemia, as well as the effect of individual or combined
antihypertensive-hypocholesterolaemic therapy on BP control and on circulating
cholesterol. A retrospective study was performed using clinical data recorded in
the general practitioner's database. The sample included all patients, aged > or
=18 years, with BP reading or low-density lipoprotein (LDL) cholesterol
measurement recorded between January 2003 and December 2004. BP and LDL
cholesterol targets were defined using cutoffs based on the guidelines of the
Joint National Committee on Prevention, Detection, Evaluation and Treatment of
High Blood Pressure (JNC7) and the National Cholesterol Education Program
(NCEP/ATPIII). The study included 4764 patients (mean age 67.6+/-11.8 years,
43.5% males). Target BP was achieved in a higher number of patients under
combined antihypertensive-hypocholesterolaemic therapy than in those treated only
with antihypertensives: 57.0 vs 50.0% in patients with history of
cardio/cerebrovascular (CV) hospitalization, 27.0 vs 16.9% in patients with
diabetes or chronic renal insufficiency (CRI) and 59.7 vs 49.1% in patients with
no CV hospitalization nor diabetes and nor CRI. The LDL cholesterol target was
achieved in 61.3% of the subjects: it was independent on the therapy (individual
or combined), but related to the degree of cardiovascular risk. Analysing the
data contained in the general medicine database made it possible to evaluate the
treatment of high BP and hypercholesterolaemia in relation to cardiovascular risk
in clinical practice and to establish the need to pay greater attention to
achieving the objective set by guidelines.
PMID- 17036043
TI - Prevalence and clinical implications of the inter-arm blood pressure difference:
A systematic review.
AB - A blood pressure (BP) difference between arms was first reported over 100 years
ago. Knowledge of its prevalence and relevance to the accurate measurement of BP
remains poor. Current hypertension guidelines do not emphasise it. The objectives
of this study were to establish the best estimate of prevalence of the inter-arm
difference (IAD) in the population, to consider its implications for accurate BP
measurement and treatment, and to discuss its aetiology and potential as a risk
marker for cardiovascular disease. Systematic literature review was carried out.
The data sources were Medline EMBASE and CINAHL databases, and Index of Theses.
Studies reporting prevalence rates of IAD were retrieved and considered for
inclusion against explicit methodological criteria. Point prevalence rates were
extracted and weighted mean prevalence rates calculated. The main outcome
measures were weighted mean prevalences of systolic IAD > or =10 and > or =20 mm
Hg and of diastolic IAD > or =10 mm Hg. Thirty-one studies were identified. Most
had methodological weaknesses; only four met the inclusion criteria. Pooled
prevalences of the IAD from these four studies were 19.6% systolic > or =10 mm Hg
(95% CI 18.0-21.3%), 4.2% systolic > or =20 mm Hg (95% CI 3.4-5.1%) and 8.1%
diastolic > or =10 mm Hg (95%CI 6.9-9.2%). In conclusion, an IAD is present in a
substantial number of patients and should be looked for whenever diagnosis and
treatment depend on accurate measurements of BP. The importance of an IAD should
be better emphasised in current hypertension management guidelines. There is
evidence associating an IAD with peripheral vascular disease, raising the
possibility that its presence may predict cardiovascular events.
PMID- 17036044
TI - Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and
9G8.
AB - The sequence-specific RNA-binding proteins SRp20 and 9G8 are the smallest members
of the serine- and arginine-rich (SR) protein family, well known for their role
in splicing. They also play a role in mRNA export, in particular of histone
mRNAs. We present the solution structures of the free 9G8 and SRp20 RNA
recognition motifs (RRMs) and of SRp20 RRM in complex with the RNA sequence
5'CAUC3'. The SRp20-RNA structure reveals that although all 4 nt are contacted by
the RRM, only the 5' cytosine is primarily recognized in a specific way. This
might explain the numerous consensus sequences found by SELEX (systematic
evolution of ligands by exponential enrichment) for the RRM of 9G8 and SRp20.
Furthermore, we identify a short arginine-rich peptide adjacent to the SRp20 and
9G8 RRMs, which does not contact RNA but is necessary and sufficient for
interaction with the export factor Tip-associated protein (TAP). Together, these
results provide a molecular description for mRNA and TAP recognition by SRp20 and
9G8.
PMID- 17036045
TI - An extended consensus motif enhances the specificity of substrate modification by
SUMO.
AB - Protein modification by SUMO conjugation is an important regulatory event.
Sumoylation usually takes place on a lysine residue embedded in the core
consensus motif psiKxE. However, this motif confers limited specificity on the
sumoylation process. Here, we have probed the roles of clusters of acidic
residues located downstream from the core SUMO modification sites in proteins
such as the transcription factor Elk-1. We demonstrate that these are
functionally important in SUMO-dependent transcriptional repression of Elk-1
transcriptional activity. Mechanistically, the acidic residues are important in
enhancing the efficiency of Elk-1 sumoylation by Ubc9. Similar mechanisms operate
in other transcription factors and phosphorylation sites can functionally
substitute for acidic residues. Thus, an extended sumoylation motif, termed the
NDSM (negatively charged amino acid-dependent sumoylation motif), helps define
functional SUMO targets. We demonstrate that this extended motif can be used to
correctly predict novel targets for SUMO modification.
PMID- 17036046
TI - Six2 is required for suppression of nephrogenesis and progenitor renewal in the
developing kidney.
AB - During kidney development and in response to inductive signals, the metanephric
mesenchyme aggregates, becomes polarized, and generates much of the epithelia of
the nephron. As such, the metanephric mesenchyme is a renal progenitor cell
population that must be replenished as epithelial derivatives are continuously
generated. The molecular mechanisms that maintain the undifferentiated state of
the metanephric mesenchymal precursor cells have not yet been identified. In this
paper, we report that functional inactivation of the homeobox gene Six2 results
in premature and ectopic differentiation of mesenchymal cells into epithelia and
depletion of the progenitor cell population within the metanephric mesenchyme.
Failure to renew the mesenchymal cells results in severe renal hypoplasia. Gain
of Six2 function in cortical metanephric mesenchymal cells was sufficient to
prevent their epithelial differentiation in an organ culture assay. We propose
that in the developing kidney, Six2 activity is required for maintaining the
mesenchymal progenitor population in an undifferentiated state by opposing the
inductive signals emanating from the ureteric bud.
PMID- 17036047
TI - Cap-free structure of eIF4E suggests a basis for conformational regulation by its
ligands.
AB - The activity of the eukaryotic translation initiation factor eIF4E is modulated
through conformational response to its ligands. For example, eIF4G and eIF4E
binding proteins (4E-BPs) modulate cap affinity, and thus physiological activity
of eIF4E, by binding a site distal to the 7-methylguanosine cap-binding site.
Further, cap binding substantially modulates eIF4E's affinity for eIF4G and the
4E-BPs. To date, only cap-bound eIF4E structures were reported. In the absence of
structural information on the apo form, the molecular underpinnings of this
conformational response mechanism cannot be established. We report here the first
cap-free eIF4E structure. Apo-eIF4E exhibits structural differences in the cap
binding site and dorsal surface relative to cap-eIF4E. Analysis of structure and
dynamics of apo-eIF4E, and changes observed upon ligand binding, reveal a
molecular basis for eIF4E's conformational response to these ligands. In
particular, alterations in the S4-H4 loop, distal to either the cap or eIF4G
binding sites, appear key to modulating these effects. Mutation in this loop
mimics these effects. Overall, our studies have important implications for the
regulation of eIF4E.
PMID- 17036048
TI - Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP
gated P2X7 receptor.
AB - P2X(7) receptors are ATP-gated cation channels; their activation in macrophage
also leads to rapid opening of a membrane pore permeable to dyes such as
ethidium, and to release of the pro-inflammatory cytokine, interleukin-1beta (IL
1beta). It has not been known what this dye-uptake path is, or whether it is
involved in downstream signalling to IL-1beta release. Here, we identify pannexin
1, a recently described mammalian protein that functions as a hemichannel when
ectopically expressed, as this dye-uptake pathway and show that signalling
through pannexin-1 is required for processing of caspase-1 and release of mature
IL-1beta induced by P2X(7) receptor activation.
PMID- 17036049
TI - Myelin basic protein-dependent plasma membrane reorganization in the formation of
myelin.
AB - During vertebrate development, oligodendrocytes wrap their plasma membrane around
axons to produce myelin, a specialized membrane highly enriched in
galactosylceramide (GalC) and cholesterol. Here, we studied the formation of
myelin membrane sheets in a neuron-glia co-culture system. We applied different
microscopy techniques to visualize lipid packing and dynamics in the
oligodendroglial plasma membrane. We used the fluorescent dye Laurdan to examine
the lipid order with two-photon microscopy and observed that neurons induce a
dramatic lipid condensation of the oligodendroglial membrane. On a nanoscale
resolution, using stimulated emission depletion and fluorescence resonance energy
transfer microscopy, we demonstrated a neuronal-dependent clustering of GalC in
oligodendrocytes. Most importantly these changes in lipid organization of the
oligodendroglial plasma membrane were not observed in shiverer mice that do not
express the myelin basic protein. Our data demonstrate that neurons induce the
condensation of the myelin-forming bilayer in oligodendrocytes and that MBP is
involved in this process of plasma membrane rearrangement. We propose that this
mechanism is essential for myelin to perform its insulating function during nerve
conduction.
PMID- 17036050
TI - New p63 targets in keratinocytes identified by a genome-wide approach.
AB - p63 is a developmentally regulated transcription factor related to p53. It is
involved in the development of ectodermal tissues, including limb, skin and in
general, multilayered epithelia. The DeltaNp63alpha isoform is thought to play a
'master' role in the asymmetric division of epithelial cells. It is also involved
in the pathogenesis of several human diseases, phenotypically characterized by
ectodermal dysplasia. Our understanding of transcriptional networks controlled by
p63 is limited, owing to the low number of bona fide targets. To screen for new
targets, we employed chromatin immunoprecipitation from keratinocytes (KCs)
coupled to the microarray technology, using both CpG islands and promoter arrays.
The former revealed 96 loci, the latter yielded 85 additional genes. We tested 40
of these targets in several functional assays, including: (i) in vivo binding by
p63 in primary KCs; (ii) expression analysis in differentiating HaCaT cells and
in cells overexpressing DeltaNp63alpha; (iii) promoter transactivation and (iv)
immunostaining in normal tissues, confirming their regulation by p63. We
discovered several new specific targets whose functional categorization links p63
to cell growth and differentiation.
PMID- 17036051
TI - In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding domain
heterodimer.
AB - The human ATP-binding cassette (ABC) protein CFTR (cystic fibrosis transmembrane
conductance regulator) is a chloride channel, whose dysfunction causes cystic
fibrosis. To gain structural insight into the dynamic interaction between CFTR's
nucleotide-binding domains (NBDs) proposed to underlie channel gating, we
introduced target cysteines into the NBDs, expressed the channels in Xenopus
oocytes, and used in vivo sulfhydryl-specific crosslinking to directly examine
the cysteines' proximity. We tested five cysteine pairs, each comprising one
introduced cysteine in the NH(2)-terminal NBD1 and another in the COOH-terminal
NBD2. Identification of crosslinked product was facilitated by co-expression of
NH(2)-terminal and COOH-terminal CFTR half channels each containing one NBD. The
COOH-terminal half channel lacked all native cysteines. None of CFTR's 18 native
cysteines was found essential for wild type-like, phosphorylation- and ATP
dependent, channel gating. The observed crosslinks demonstrate that NBD1 and NBD2
interact in a head-to-tail configuration analogous to that in homodimeric crystal
structures of nucleotide-bound prokaryotic NBDs. CFTR phosphorylation by PKA
strongly promoted both crosslinking and opening of the split channels, firmly
linking head-to-tail NBD1-NBD2 association to channel opening.
PMID- 17036052
TI - A nestin scaffold links Cdk5/p35 signaling to oxidant-induced cell death.
AB - The intermediate filament protein, nestin, has been implicated as an organizer of
survival-determining signaling molecules. When nestin expression was related to
the sensitivity of neural progenitor cells to oxidant-induced apoptosis, nestin
displayed a distinct cytoprotective effect. Oxidative stress in neuronal
precursor cells led to downregulation of nestin with subsequent activation of
cyclin-dependent kinase 5 (Cdk5), a crucial kinase in the nervous system. Nestin
downregulation was a prerequisite for the Cdk5-dependent apoptosis, as
overexpression of nestin efficiently inhibited induction of apoptosis, whereas
depletion of nestin by RNA interference had a sensitizing effect. When the
underlying link between nestin and Cdk5 was analyzed, we observed that nestin
serves as a scaffold for Cdk5, with binding restricted to a specific region
following the alpha-helical domain of nestin, and that the presence and
organization of nestin regulated the sequestration and activity of Cdk5, as well
as the ubiquitylation and turnover of its regulator, p35. Our data imply that
nestin is a survival determinant whose action is based upon a novel mode of Cdk5
regulation, affecting the targeting, activity, and turnover of the Cdk5/p35
signaling complex.
PMID- 17036053
TI - Epigenetic determination of a cell-specific gene expression program by ATF-2 and
the histone variant macroH2A.
AB - Transcriptional activation of the interleukin-8 (IL-8) gene is restricted to
distinct cell types, although the transcriptional regulatory proteins controlling
IL-8 gene expression are ubiquitous. We show that cell-specific transcription of
IL-8 is due to the distinct chromatin architecture on the enhancer/promoter
before the arrival of the inducing signal. In expressing epithelial cells the
enhancer/promoter is nucleosome-free, whereas in non-expressing B cells a
nucleosome masks the entire regulatory region. The B-cell-specific nucleosome
contains the histone variant macroH2A, which is responsible for preventing
transcription factor binding. Recruitment of the repressive macroH2A nucleosome
requires direct interactions between ATF-2 bound to the nearby AP1 site and
macroH2A and it is regulated by DNA-induced protein allostery. siRNA against ATF
2 or macroH2A rescues IL-8 transcription in B cells. Thus, a transcription factor
can work as a transcriptional repressor by orchestrating and maintaining the
assembly of specialized local chromatin architectures.
PMID- 17036054
TI - Microtubule depolymerization can drive poleward chromosome motion in fission
yeast.
AB - Prometaphase kinetochores interact with spindle microtubules (MTs) to establish
chromosome bi-orientation. Before becoming bi-oriented, chromosomes frequently
exhibit poleward movements (P-movements), which are commonly attributed to minus
end-directed, MT-dependent motors. In fission yeast there are three such motors:
dynein and two kinesin-14s, Pkl1p and Klp2p. None of these enzymes is essential
for viability, and even the triple deletion grows well. This might be due to the
fact that yeasts kinetochores are normally juxtapolar at mitosis onset, removing
the need for poleward chromosome movement during prometaphase. Anaphase P
movement might also be dispensable in a spindle that elongates significantly. To
test this supposition, we have analyzed kinetochore dynamics in cells whose
kinetochore-pole connections have been dispersed. In cells recovering from this
condition, the maximum rate of poleward kinetochore movement was unaffected by
the deletion of any or all of these motors, strongly suggesting that other
factors, like MT depolymerization, can cause such movements in vivo. However,
Klp2p, which localizes to kinetochores, contributed to the effectiveness of P
movement by promoting the shortening of kinetochore fibers.
PMID- 17036055
TI - The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand
DNA crosslinks into double-strands breaks.
AB - Repair of interstrand crosslinks (ICLs) requires multiple-strand incisions to
separate the two covalently attached strands of DNA. It is unclear how these
incisions are generated. DNA double-strand breaks (DSBs) have been identified as
intermediates in ICL repair, but enzymes responsible for producing these
intermediates are unknown. Here we show that Mus81, a component of the Mus81-Eme1
structure-specific endonuclease, is involved in generating the ICL-induced DSBs
in mouse embryonic stem (ES) cells in S phase. Given the DNA junction cleavage
specificity of Mus81-Eme1 in vitro, DNA damage-stalled replication forks are
suitable in vivo substrates. Interestingly, generation of DSBs from replication
forks stalled due to DNA damage that affects only one of the two DNA strands did
not require Mus81. Furthermore, in addition to a physical interaction between
Mus81 and the homologous recombination protein Rad54, we show that Mus81(-/-)
Rad54(-/-) ES cells were as hypersensitive to ICL agents as Mus81(-/-) cells. We
propose that Mus81-Eme1- and Rad54-mediated homologous recombination are involved
in the same DNA replication-dependent ICL repair pathway.
PMID- 17036056
TI - Decreased immune reactivity towards a knobless, affibody-targeted adenovirus type
5 vector.
AB - In this study, a prototype Adenovirus type 5 (Ad5) vector deleted of the fiber
knob domain and carrying an Affibody molecule as the targeting ligand showed
decreased susceptibility to human pre-existing antibodies. This vector, Ad5/R7
Z(taq)Z(taq), has short fibers carrying seven shaft repeats, a non-native
trimerization signal and an affibody molecule (Z(taq)) reactive to Taq
polymerase. Ad5/R7-Z(taq)Z(taq) could be specifically targeted to 293 cells
stably expressing membrane-bound anti-Z(taq) idiotypic affibody called Z(ztaq)
(293Z(ztaq)). Sera from 50 blood donors were analyzed for neutralization activity
(NA) against the parental Ad5/Fiwt vector and knobless Ad5/R7-Z(taq)Z(taq) on
293Z(ztaq) cells. Twenty-three sera had NA titers (> or =1:64) against Ad5/Fiwt
(46%) and only two against Ad5/R7-Z(taq)Z(taq) (4%). Characterization of sera
with NA titers showed that the knob domain is one of the targets of the
antibodies. Neutralization assays using sera pre-adsorbed on knob and hexon
proteins showed that the NA of the sera was carried mainly by anti-knob and anti
hexon antibodies, but in certain sera the anti-hexon antibodies represent the
major population of the neutralizing antibodies (NAbs). Our results suggested
that a combination of knob deletion and hexon switching could be an effective
strategy for Ad vectors to better evade the anti-Ad NAbs.
PMID- 17036057
TI - Dendritic cells transfected with interleukin-12 and tumor-associated antigen
messenger RNA induce high avidity cytotoxic T cells.
AB - Dendritic cells (DC) transfected with messenger RNA (mRNA) encoding tumor
associated antigens (TAA) are able to induce potent tumor-specific T-cell
responses directed to a broad spectrum of tumor-associated epitopes. The in vitro
generation of DC possessing all the features crucial for the induction of type 1
immune responses, such as mature state, migratory potential and interleukin-12
(IL-12p70) production is complicated. Particularly migratory potential is
inversely correlated with IL-12p70 production after maturation with prostaglandin
E2 (PGE2), which is included in maturation cocktails currently used in most
vaccination trials. Here, we show that transfection of PGE2 matured DC with a
single mRNA strain encoding for ubiquitin followed by a TAA which was linked to
IL-12 by a self-cleaving 2A sequence, produced biological active IL-12p70 and
were able to present the transfected TAA up to 72 h after transfection.
Furthermore, use of the anti-reverse cap analog for in vitro transcription of the
IL-12 mRNA enabled constitutive IL-12p70 production for up to 5 days. These
transfected mature DC migrated efficiently towards lymph node derived chemokines.
DCs constitutively expressing IL-12p70, generate TAA-specific cytotoxic T cells
with an high functional avidity, independent of CD4+ T-cell help.
PMID- 17036058
TI - Pig liver gene therapy by noninvasive interventionist catheterism.
AB - The efficacy of noninvasive interventionist catheterism in large animals as an
alternative to the hydrodynamic procedure, described for small animals, is
evaluated. Basically, gene transfer is performed by implantation and fixation of
a balloon catheter within the suprahepatic vein of anesthetized pigs, through the
femoral vein. The catheter tip is identified by fluoroscopy, injecting a contrast
solution that marks large or small hepatic territories. Animals were injected
with a 100 ml pTG7101 plasmid solution (40 microg/ml), which contains the human
alpha-1 antitrypsin gene, perfused at a rate of 7.5 ml/s and efficacy and
toxicity of the procedure were evaluated. The results show: (i) the highest
efficacy in protein production is reached when perfusion is limited to small
areas of the liver; (ii) no relevant hepatic toxicity was observed; (iii) gene
transfer is mainly located in the areas around the central vein, as seen in the
immunohistochemical studies; (iv) the electron microscopy studies indicate that
the areas with good transfection efficacy show the presence of abundant endocytic
vesicles that may even fuse among themselves. These data suggest that retrovenous
injection by noninvasive interventionist catheterism could become an efficient
procedure for hepatic gene transfer with potential clinical applications.
PMID- 17036059
TI - The ripples of "The Big (agricultural) Bang": the spread of early wheat
cultivation.
AB - Demographic expansion and (or) migrations leave their mark in the pattern of DNA
polymorphisms of the respective populations. Likewise, the spread of cultural
phenomena can be traced by dating archaeological finds and reconstructing their
direction and pace. A similar course of events is likely to have taken place
following the "Big Bang" of the agricultural spread in the Neolithic Near East
from its core area in southeastern Turkey. Thus far, no attempts have been made
to track the movement of the founder genetic stocks of the first crop plants from
their core area based on the genetic structure of living plants. In this
minireview, we re-interpret recent wheat DNA polymorphism data to detect the
genetic ripples left by the early wave of advance of Neolithic wheat farming from
its core area. This methodology may help to suggest a model charting the spread
of the first farming phase prior to the emergence of truly domesticated wheat
types (and other such crops), thereby increasing our resolution power in studying
this revolutionary period of human cultural, demographic, and social evolution.
PMID- 17036060
TI - Haplotype characterization and markers at the barley Mlo powdery mildew
resistance locus as tools for marker-assisted selection.
AB - Recessive mlo alleles of the barley Mlo gene confer resistance to almost all
known isolates of the powdery mildew fungal pathogen targeting barley (Hordeum
vulgare). To characterize haplotypes present in the Mlo chromosomal region of
cultivated Mlo and mlo barley genotypes, we conducted a polymorphism search in 3
predicted low-copy sequence regions adjacent to the Mlo gene by examining a
sample of 4 Mlo and 3 mlo cultivars. Eight single-nucleotide polymorphisms (SNPs)
and 1 insertion-deletion (indel) were detected, and easy to use PCR-based markers
were developed for typing the SNPs. The PCR markers were used to characterize a
collection of 46 Mlo and 25 mlo barley cultivars, identifying 3 distinct mlo-11
haplotypes, 1 mlo-9 haplotype, and 4 Mlo haplotypes. We summarized the haplotype
and marker information obtained here and in a previous study to help breeders
identify strategies for mlo marker-assisted selection. The ability of the markers
to identify mlo-resistant genotypes in segregating populations was demonstrated
using 2 resistance-characterized F2 populations derived by 3-way crosses.
PMID- 17036061
TI - Genetic analysis and molecular mapping of the avirulence gene PRE1, a gene for
host-species specificity in the blast fungus Magnaporthe grisea.
AB - We analyzed host-species specificity of Magnaporthe grisea on rice using 110 F1
progeny derived from a cross between the Oryza isolate CH87 (pathogenic to rice)
and the Digitaria isolate 6023 (pathogenic to crabgrass). To elucidate the
genetic mechanisms controlling species specificity in M. grisea, we performed a
genetic analysis of species-specific avirulence on this rice population.
Avirulent and virulent progeny segregated in a 1:1 ratio on the 2 rice cultivars
'Lijiangxintuanheigu' (LTH) and 'Shin2', suggesting that a single locus,
designated PRE1, was involved in the specificity. In a combination between
'Kusabue' and 'Tsuyuake', the segregation of the 4 possible phenotypes of F1
progeny was significantly different from the expected 3:1:3:1 and instead fit a
ratio of 2:0:1:1. This indicated that 2 loci, PRE1 and AVR2, were involved in
specific parasitism on rice. These results suggest that the species specificity
of M. grisea on rice is governed by species-dependent genetic mechanisms that are
similar to the gene-for-gene interactions controlling cultivar specificity.
Pathogenicity tests with various plant species revealed that the Digitaria
isolate 6023 was exclusively parasitic on crabgrass. Genetic linkage analysis
showed that PRE1 was mapped on chromosome 3 with respect to RAPD and SSR markers.
RAPD marker S361 was linked to the avirulence gene at a distance of ~6.4 cM. Two
SSR markers, m677-678 and m77-78, were linked to the PRE1 gene on M. grisea
chromosome 3 at distances of 5.9 and 7.1 cM, respectively. Our results will
facilitate positional cloning and functional studies of this gene.
PMID- 17036063
TI - Molecular characterization of ribosomal intergenic spacer in the tadpole shrimp
Triops cancriformis (Crustacea, Branchiopoda, Notostraca).
AB - Nuclear ribosomal DNA constitutes a multigene family, with tandemly arranged
units linked by an intergenic spacer (IGS), which contains initiation/termination
transcription signals and usually tandemly arranged subrepeats. The structure and
variability of the IGS region are analyzed here in hermaphroditic and
parthenogenetic populations of the "living fossil" Triops cancriformis
(Branchiopoda, Notostraca). The results indicate the presence of concerted
evolution at the population level for this G+C-rich IGS region as a whole, with
the major amount of genetic variability found outside the subrepeat region. The
subrepeats region is composed of 3 complete repeats (a, c, d) intermingled with 3
repeat fragments (b, e, f) and unrelated sequences. The most striking datum is
the absolute identity of subrepeats (except type d) occupying the same position
in different individuals/populations. A putative promoter sequence is present
upstream of the 18S rRNA gene, but not in subrepeats, which is at variance with
other arthropod IGSs. The absence of a promoter sequence in the subrepeats and
subrepeat sequence conservation suggests that this region acts as an enhancer
simply by its repetitive nature, as observed in some vertebrates. The putative
external transcribed spacer (840 bp) shows hairpin structures, as in yeasts,
protozoans, Drosophila, and vertebrates.
PMID- 17036064
TI - Determination of mRNA half-lives in Candida albicans using thiolutin as a
transcription inhibitor.
AB - A method for determining mRNA half-lives in the polymorphic fungus Candida
albicans is described. It employs growth in a defined medium, the inhibition of
transcription with thiolutin (10-20 microg/mL), and quantitative Northern
blotting. The method is effective for the A72, SC5314, and CAI-4 strains of C.
albicans, and for mRNAs that have a wide variety of decay rates and steady-state
abundances. The range of half-lives detected (from 4-168 min) shows that this
method is effective for mRNAs with widely varying half-lives. The mRNA decay
rates obtained are compared with those for orthologous mRNAs from Saccharomyces
cerevisiae. This procedure should work for a broad range of C. albicans strains
and can be adapted to other fungal species.
PMID- 17036065
TI - Distributional gradient of amino acid repeats in plant proteins.
AB - A computer-based analysis was conducted to assess the characteristics of amino
acid repeats in Arabidopsis and rice. Our analysis showed a negative gradient in
amino acid repeat distribution along the direction of translation in plants.
Repeat occurrences are obviously associated with position in plant proteins but
are not consistent with the corresponding amino acid contents. These repeats are
encoded by the mixed synonymous codons rather than the uninterrupted reiterations
of a single codon, and both Arabidopsis and rice have gradients in their
distribution. Functional investigation showed that these repeat-containing
proteins are preferentially involved in transcription regulation and protein
ubiquitination but significantly underrepresented in the processes of DNA
recombination and DNA replication. These data reveal that the direction-related
mutation bias and functional selection have influenced the distribution of amino
acid repeats in plants.
PMID- 17036066
TI - Genetic diversity among varieties of the native forage grass Trichloris crinita
based on AFLP markers, morphological characters, and quantitative agronomic
traits.
AB - We assessed the genetic diversity in Trichloris crinita (Poaceae) varieties from
South America, using AFLPs, morphological characters, and quantitative agronomic
traits. Owing to the importance of this species for range grazing, we first
characterized the varieties based on forage productivity. Biomass production
varied 9 fold among the materials evaluated. Analysis of AFLP fingerprints
allowed the discrimination of all varieties with a few selected primer
combinations. Pair-wise genetic similarities, using marker data, ranged from 0.31
to 0.92 (Jaccard coefficients). Marker-based unweighted pair group method with
arithmetic averaging (UPGMA) cluster analysis did not show geographical
clustering, but rather grouped the varieties according to their biomass
production. We identified 18 markers associated with biomass production, of which
8 showed complete correlation (r = 1.00) with this trait. These DNA markers can
be used to assist selection for high forage productivity in T. crinita. Cluster
analysis using morphological and quantitative characters revealed 4 distinct
groups of varieties, clearly separated according to their biomass yield. The
variables foliage height and basal diameter were strongly correlated with biomass
production and these phenotypic markers can be used to select productive plants.
The relations among the varieties based on AFLP data were significantly
correlated with those based on agronomic and morphological characters, suggesting
that the 2 systems give similar estimates of genetic relations among the
varieties.
PMID- 17036067
TI - Assessment of genetic diversity in cultivars of white clover (Trifolium repens
L.) detected by SSR polymorphisms.
AB - White clover (Trifolium repens L.) is an important temperate pasture legume that
plays a key role as a companion to grass species, such as perennial ryegrass
(Lolium perenne L.). Due to the outbreeding nature of white clover, cultivars are
highly heterogeneous. Genetic diversity was assessed using 16 elite cultivars
from Europe, North and South America, Australia, and New Zealand. Fifteen simple
sequence repeat markers that detect single, codominant polymorphic genetic loci
were selected for the study. The genetic relationships among individuals were
compared using phenetic clustering, and those among cultivars were compared using
nonmetric multidimensional scaling. Intrapopula tion variability exceeded
interpopulation variability, with substantial overlap among populations and weak
interpopula tion differentiation. No obvious or significant differentiation was
observed on the basis of morphology or geographic origin of the cultivars. The
number of parental genotypes used to derive each cultivar was not a major
determinant of genome-wide genetic diversity. The outcomes of this assessment of
genetic variation in elite white clover germplasm pools have important
implications for the feasibility of molecular marker-based cultivar
discrimination, and will be used to assist the design of linkage disequilibrium
mapping strategies for marker-trait association.
PMID- 17036068
TI - Structural organization of the mitochondrial DNA control region in Aedes aegypti.
AB - The complete A+T - rich region of Aedes aegypti mitochondrial DNA has been cloned
and sequenced. In Argentinean populations of the species, a polymorphism in the
length of the amplified fragment was observed. Nucleotide sequence comparison of
the shortest and longest A+T - rich amplified fragments detected revealed the
presence of 2 types of tandemly repeated blocks. The size variation observed in
natural populations is mainly due to the presence of a variable number of a 181
bp tandem repeat unit, located toward the 12S rRNA gene end. The size of the
longest A+T - rich region was of 2070 bp, representing the largest control
sequence reported for any mosquito species. Few relevant short blocks of primary
sequence similarity conserved in the control region of mosquitoes and other
insects were detected scattered throughout the whole region. Five putative stem
loop secondary structures were found, one of them flanked by conserved sequences
described in other insects. Our results suggest that there are no universal
models of structure-function relations in the control region of insect mtDNA. In
addition, we identified a short A+T - rich variable segment in the Ae. aegyti
control region that would be suitable for population genetic studies.
PMID- 17036069
TI - Molecular marker diversity of SCN-resistant sources in soybean.
AB - Soybean cyst nematode (SCN) (Heterodera glycines Ichinohe; HG) is one of the most
destructive pests of soybean (Glycine max (L.) Merr.) in the United States. Over
100 SCN-resistant accessions within the USDA Soybean Germplasm Collection have
been identified, but little is known about the genetic diversity of this SCN
resistant germplasm. The objective of this research was to evaluate the genetic
variation and determine the genetic relationships among SCN-resistant accessions.
One hundred twenty-two genotypes were evaluated by 85 simple sequence repeat
(SSR) markers from 20 linkage groups. Non-hierarchical (VARCLUS) and hierarchical
(Ward's) clustering were combined with multidimensional scaling (MDS) to
determine relationships among tested lines. The 85 SSR markers produced 566
allelic fragments with a mean polymorphic information content (PIC) value of
0.35. The 122 lines were grouped into 7 clusters by 2 different clustering
methods and the MDS results consistently corresponded to the assigned clusters.
Assigned clusters were dominated by genotypes that possess one or more unique SCN
resistance genes and were associated with geographical origins. The results of
analysis of molecular variance (AMOVA) showed that the variation differences
among clusters and individual lines were significant, but the differences among
individuals within clusters were not significant.
PMID- 17036070
TI - Timing and rate of genome variation in triticale following allopolyploidization.
AB - The timing and rate of genomic variation induced by allopolyploidization in the
intergeneric wheat-rye (Triticum spp. - Secale cereale L.) hybrid triticale (x
Triticosecale Wittmack) was studied using amplified fragment length polymorphism
(AFLP) analyses with 2 sets of primers, EcoRI-MseI (E-M) and PstI-MseI (P-M),
which primarily amplify repetitive and low-copy sequences, respectively. The
results showed that allopolyploidization induced genome sequence variation in
triticale and that a great degree of the genome variation occurred immediately
following wide hybridization. Specifically, about 46.3% and 36.2% of the wheat
parental band loss and 74.5% and 68.4% of the rye parental band loss occurred in
the F1 hybrids (before chromosome doubling) for E-M and P-M primers,
respectively. The sequence variation events that followed chromosome doubling
consisted of continuous modifications that occurred at a very small rate compared
with the rate of variation before chromosome doubling. However, the rate of
sequence variation involving the rye parental genome was much higher in the first
5 generations following chromosome doubling than in any subsequent generation.
Surprisingly, the highest rate of rye genomic variation occurring after
chromosome doubling was in C3 or later, but not in C1. The data suggested that
the cytoplasm and the degree of the relationship between the parental genomes
were the key factors in determining the direction, amount, timing, and rate of
genomic sequence variation occurring during intergeneric allopolyploidization.
PMID- 17036062
TI - Analysis of expressed sequence tags from a naked foraminiferan Reticulomyxa
filosa.
AB - Foraminifers are a major component of modern marine ecosystems and one of the
most important oceanic producers of calcium carbonate. They are a key
phylogenetic group among amoeboid protists, but our knowledge of their genome is
still mostly limited to a few conserved genes. Here, we report the first study of
expressed genes by means of expressed sequence tag (EST) from the freshwater
naked foraminiferan Reticulomyxa filosa. Cluster analysis of 1630 valid ESTs
enabled the identification of 178 groups of related sequences and 871 singlets.
Approximately 50% of the putative unique 1059 ESTs could be annotated using Blast
searches against the protein database SwissProt + TrEMBL. The EST database
described here is the first step towards gene discovery in Foraminifera and
should provide the basis for new insights into the genomic and transcriptomic
characteristics of these interesting but poorly understood protists.
PMID- 17036071
TI - Development and linkage mapping of E-STS and RGA markers for functional gene
homologues in apple.
AB - Linkage maps developed from known-function genes can be valuable in the candidate
gene mapping approach. A set of 121 expressed sequence tagged site (E-STS) primer
pairs were tested on a framework genetic linkage map of apple (Malus x domestica
Borkh.) constructed using simple sequence repeats (SSRs) and randomly amplified
polymorphic DNA (RAPD) markers. These known-function gene markers, E-STSs, were
supplemented by markers for resistance gene analogues (RGAs), designed based on
conserved motifs in all characterized resistance genes isolated from plant
species. A total of 229 markers, including 46 apple E-STSs, 8 RGAs, 85 SSRs from
apple and peach, and 88 RAPDs, were assigned to 17 linkage groups covering 832 cM
of the apple genome, based on 52 individuals originating from the cross
'Antonovka debnicka' (Q12-4) x 'Summerred'. Clusters of E-STS and RGA loci were
located in linkage groups previously identified to carry resistance genes, some
of which confer resistance to apple scab disease caused by Venturia inaequalis
(Cke.) Wint.
PMID- 17036072
TI - Isolation, characterization, and linkage analyses of 74 novel microsatellites in
Barramundi (Lates calcarifer).
AB - Barramundi (Lates calcarifer) is an important marine food fish species in
Southeast Asia and Australia. Seventy-four novel microsatellites were isolated
from a genomic DNA library enriched for CA repeats and were characterized in 24
unrelated individuals. Among the 74 microsatellites, 71 were polymorphic, with an
average allele number of 7.0 +/- 3.6/locus. The average expected heterozygosity
of these polymorphic markers was 0.66. Sixty-three of the 71 polymorphic
microsatellites conformed to Hardy-Weinberg equilibrium. Linkage analyses were
conducted in a reference family, leading to the assignment of 34 novel
microsatellites and 16 published markers in 16 linkage groups. The novel
microsatellites developed in this study will contribute significantly to the
construction of a first-generation linkage map for mapping of quantitative trait
loci in Barramundi, and supply a large choice of markers for studies on
population genetics, stock management, and pedigree reconstruction.
PMID- 17036073
TI - Characterization of genetic loci conferring adult plant resistance to leaf rust
and stripe rust in spring wheat.
AB - Leaf (brown) and stripe (yellow) rusts, caused by Puccinia triticina and Puccinia
striiformis, respectively, are fungal diseases of wheat (Triticum aestivum) that
cause significant yield losses annually in many wheat-growing regions of the
world. The objectives of our study were to characterize genetic loci associated
with resistance to leaf and stripe rusts using molecular markers in a population
derived from a cross between the rust-susceptible cultivar 'Avocet S' and the
resistant cultivar 'Pavon76'. Using bulked segregant analysis and partial linkage
mapping with AFLPs, SSRs and RFLPs, we identified 6 independent loci that
contributed to slow rusting or adult plant resistance (APR) to the 2 rust
diseases. Using marker information available from existing linkage maps, we have
identified additional markers associated with resistance to these 2 diseases and
established several linkage groups in the 'Avocet S' x 'Pavon76' population. The
putative loci identified on chromosomes 1BL, 4BL, and 6AL influenced resistance
to both stripe and leaf rust. The loci on chromosomes 3BS and 6BL had significant
effects only on stripe rust, whereas another locus, characterized by AFLP
markers, had minor effects on leaf rust only. Data derived from Interval mapping
indicated that the loci identified explained 53% of the total phenotypic
variation (R2) for stripe rust and 57% for leaf rust averaged across 3 sets of
field data. A single chromosome recombinant line population segregating for
chromosome 1B was used to map Lr46/Yr29 as a single Mendelian locus.
Characterization of slow-rusting genes for leaf and stripe rust in improved wheat
germplasm would enable wheat breeders to combine these additional loci with known
slow-rusting loci to generate wheat cultivars with higher levels of slow-rusting
resistance.
PMID- 17036074
TI - Developmental characterization of the fasciated locus and mapping of Arabidopsis
candidate genes involved in the control of floral meristem size and carpel number
in tomato.
AB - Mutation at the fasciated locus was a key step in the production of extreme fruit
size during tomato domestication. To shed light on the nature of these changes,
near-isogenic lines were used for a comparative developmental study of fasciated
and wild-type tomato plants. The fasciated gene directly affects floral meristem
size and is expressed before the earliest stages of flower organogenesis. As a
result, mature fruit of fasciated mutants have more carpels (locules) and greater
fruit diameter and mass. The discovery that fasciated affects floral meristem
size led to a search for candidate genes from Arabidopsis known to be involved in
floral meristem development. Putative homologs were identified in a large tomato
EST database, verified through phylogenetic analyses, and mapped in tomato; none
mapped to the fasciated locus; however, putative homologs of WUS and WIG mapped
to the locule number locus on chromosome 2, the second major transition to large
tomato fruit, with WUS showing the highest association. In other cases, minor
QTLs for floral organ number (lcn2.2) and (stn11.2) co-localized with a CLV1
paralog and with the syntenic region containing the CLV3 gene in Arabidopsis,
respectively.
PMID- 17036075
TI - The genome of Oscheius tipulae: determination of size, complexity, and structure
by DNA reassociation using fluorescent dye.
AB - This work describes the physicochemical characterization of the genome and
telomere structure from the nematode Oscheius tipulae CEW1. Oscheius tipulae is a
free-living nematode belonging to the family Rhabditidae and has been used as a
model system for comparative genetic studies. A new protocol that combines
fluorescent detection of double-stranded DNA and S1 nuclease was used to
determine the genome size of O. tipulae as 100.8 Mb (approximately 0.1 pg
DNA/haploid nucleus). The genome of this nematode is made up of 83.4% unique copy
sequences, 9.4% intermediate repetitive sequences, and 7.2% highly repetitive
sequences, suggesting that its structure is similar to those of other nematodes
of the genus Caenorhabditis. We also showed that O. tipulae has the same telomere
repeats already found in Caenorhabditis elegans at the ends and in internal
regions of the chromosomes. Using a cassette-ligation-mediated PCR protocol we
were able to obtain 5 different putative subtelomeric sequences of O. tipulae,
which show no similarity to C. elegans or C. briggsae subtelomeric regions. DAPI
staining of hermaphrodite gonad cells show that, as detected in C. elegans and
other rhabditids, O. tipulae have a haploid complement of 6 chromosomes.
PMID- 17036076
TI - Fine mapping of a pistilloid-stamen (PS) gene on the short arm of chromosome 1 in
rice.
AB - A novel floral organ mutant of rice (Oryza sativa L. subsp. indica), termed
pistilloid-stamen (ps) here, has flowers with degenerated lemma and palea, with
some stamens transformed into pistils and pistil-stamen chimeras. Genetic
analysis confirmed that the ps trait is controlled by a single recessive gene. F2
and F3 segregation populations derived from PS ps heterozygote crossed with Oryza
sativa subsp. indica 'Luhui-17' (PS PS) were used for molecular mapping of the
gene using simple sequence repeat (SSR) markers. With 97 recessive individuals
from an F2 segregation population, the ps locus was preliminarily mapped 6.2 cM
distal to marker RM6324 and 3.1 cM proximal to marker RM6340 in the terminal
region of the short arm of chromosome 1. With a large F3 segregation population,
the gene was fine-mapped between markers RM6470 and RM1141, at distances of 0.10
and 0.03 cM to each marker, respectively. The position of the ps gene was finally
located within a 20 kb physical region containing 3 annotated putative genes. One
of them, encoding a protein with a single C2H2 zinc-finger domain, may be the
candidate gene for PS.
PMID- 17036077
TI - Phylogenetic reconstruction of Aegilops section Sitopsis and the evolution of
tandem repeats in the diploids and derived wheat polyploids.
AB - The evolution of 2 tandemly repeated sequences Spelt1 and Spelt52 was studied in
Triticum species representing 2 evolutionary lineages of wheat and in Aegilops
sect. Sitopsis, putative donors of their B/G genomes. Using fluorescence in situ
hybridization we observed considerable polymorphisms in the hybridization
patterns of Spelt1 and Spelt52 repeats between and within Triticum and Aegilops
species. Between 2 and 28 subtelomeric sites of Spelt1 probe were detected in Ae.
speltoidies, depending on accession. From 8 to 12 Spelt1 subtelomeric sites were
observed in species of Timopheevi group (GAt genome), whereas the number of
signals in emmer/aestivum accessions was significantly less (from 0 to 6).
Hybridization patterns of Spelt52 in Ae. speltoides, Ae. longissima, and Ae.
sharonensis were species specific. Subtelomeric sites of Spelt52 repeat were
detected only in T. araraticum (T. timopheevii), and their number and chromosomal
location varied between accessions. Superimposing copy number data onto our
phylogenetic scheme constructed from RAPD data suggests 2 major independent
amplifications of Spelt52 and 1 of Spelt1 repeats in Aegilops divergence. It is
likely that the Spelt1 amplification took place in the ancient Ae. speltoides
before the divergence of polyploid wheats. The Spelt52 repeat was probably
amplified in the lineage of Ae. speltoides prior to divergence of the
allopolyploid T. timopheevii but after the divergence of T. durum. In a separate
amplification event, Spelt52 copy number expanded in the common ancestor of Ae.
longissima and Ae. sharonensis.
PMID- 17036078
TI - Identification of chromosomal fusion sites in Arabidopsis mutants using
sequential bicolour BAC-FISH.
AB - Double stranded chromosomal breaks are repaired by homologous recombination or
nonhomologous end joining (NHEJ). When broken chromosome ends are fused together
by NHEJ, the resulting dicentric chromosomes can be detected as anaphase bridges
during the subsequent mitosis. Telomeres in the absence of functional telomerase
shorten, became unprotected, and are eventually recognized by the cell repair
system as double stranded breaks. As result, chromosomes of Arabidopsis thaliana
plants that are deficient in the gene for telomerase reverse transcriptase (TERT)
are prone to chromosome fusions. We use Arabidopsis tert-/- mutants as a model
system for analyzing terminal chromosome fusions. Here we report a novel and
sensitive cytogenetic assay for the identification and characterization of
chromosome-terminal fusion events by employing fluorescence in situ hybridization
(FISH) with multiple probes and a repeated hybridization approach. A mixture of
chromosome-specific subtelomeric probes is applied successively in 3 FISH
reactions to the slides containing mitotic anaphase figures with anaphase
bridges. Each figure is registered by a CCD camera after each in situ
hybridization procedure. By comparing the signals presented on the bridge in
successive images the assessment of the particular chromosome arms involved in
fusion is possible. This experimental setup enables unambiguous identification of
individual chromosome ends employed in fusion events.
PMID- 17036079
TI - Loss of genomic imprinting in Drosophila clones.
AB - Genomic imprinting is a process that genetically distinguishes maternal and
paternal genomes, and can result in parent-of-origin-dependent monoallelic
expression of a gene that is dependent on the parent of origin. As such, an
otherwise functional maternally inherited allele may be silenced so that the gene
is expressed exclusively from the paternal allele, or vice versa. Once thought to
be restricted to mammals, genomic imprinting has been documented in angiosperm
plants (J.L. Kermicle. 1970. Genetics, 66: 69-85), zebrafish (C.C. Martin and R.
McGowan. 1995. Genet. Res. 65: 21-28), insects, and C. elegans (C.J. Bean, C.E.
Schaner, and W.G. Kelly. 2004. Nat. Genet. 36: 100-105.). In each case, it
appears to rely on differential chromatin structure. Aberrant imprinting has been
implicated in various human cancers and has been detected in a number of cloned
mammals, potentially limiting the usefulness of somatic nuclear transfer. Here we
show that genomic imprinting associated with a mini-X chromosome is lost in
Drosophila melanogaster clones.
PMID- 17036080
TI - Exact word matches in rice pseudomolecules.
AB - Using pseudomolecules of assembled genomic sequence, we computed the frequencies
of 6 to 24 bp oligonucleotide (oligo) "words" across the genome of rice (Oryza
sativa L. subsp. japonica). All oligos of 10 or fewer basepairs were repeated at
least 12 times in the genome. The percentage of unique (non-repeated) oligos
ranged from 0.1% for 12 bp oligos to 76.0% for 24 bp oligos. For three 200 kb
regions, we annotated each nucleotide position with the genome-wide frequency of
the 18 bp oligo starting at that position. These frequencies formed landscapes
consisting of high- and low-frequency zones. Low-frequency zones contained
occasional high-frequency spikes; these may represent footprints of RIM2
transposon activity. BLASTn searches of high-frequency non-SSR (simple sequence
repeat) 18 bp oligos returned few sequences from species other than rice. These
results demonstrate that, in rice, words are not randomly used between different
regions within the same genome, and indicate that words that are frequently
repeated within the rice genome tend to be unique to rice.
PMID- 17036081
TI - S16, a novel S-RNase allele in the diploid species Solanum chacoense.
AB - Wild potato species have a gametophytic self-incompatibility system controlled by
a single multiallelic S locus. In the style, the S-RNase gene codes for an allele
specific ribonuclease that is involved in the rejection of pollen that carries
the same S haplotype. This gene has 5 conserved regions (C1-C5) and highly
variable regions outside of these areas that play a role in S-RNase allele
specificity. In this work, PCR-mediated amplification of genomic DNA from 2
Solanum chacoense accessions was performed using primers designed on the basis of
the C1 and C4 conserved regions. By sequencing the PCR products, a new S-RNase
allele (S16) was identified in 1 plant of the QBCM argentinian accession.
Comparison of the partial sequence (from C2 to C3) of S16 RNase with those of 11
S-RNase genes of other Solanaceae species showed the highest and the lowest
similarity scores within the same plant species (respectively, 71% with the S11
and S13 RNase and 35% with the S2 RNase). Differences at the nucleotide level
between S16 and S11 RNase alleles are discussed.
PMID- 17036083
TI - Year in review: communicable disease surveillance, 2005.
PMID- 17036084
TI - The investigation of an outbreak of cryptosporidiosis in New South Wales in 2005.
PMID- 17036085
TI - Managing a cluster of cryptosporidiosis associated with a public swimming pool.
PMID- 17036086
TI - Genotyping of Mycobacterium tuberculosis in New South Wales: results from 18
months of a statewide trial.
PMID- 17036087
TI - Bug Breakfast in the bulletin: chlamydia, gonorrhoea and syphilis.
PMID- 17036088
TI - Communicable diseases report, New South Wales, for March and April 2006.
PMID- 17036089
TI - Perspectives that influence action plans for chronic obstructive pulmonary
disease.
AB - BACKGROUND: Prompt treatment of acute exacerbations (AEs) in chronic obstructive
pulmonary disease (COPD) improves quality of life and reduces the use of health
care resources. Although patient self-management through an individualized action
plan (AP) can help with early initiation of therapy, its use is critically
dependent on the patient recognizing the features of an exacerbation. OBJECTIVE:
To describe COPD patients' experiences with AEs, as well as health care
professionals' (HCPs') attitudes toward the provision of an AP as part of self
management education. METHODS: Thirty-two patients with moderate to severe COPD
who recently experienced at least one AE, and 22 HCPs with experience in the
management of COPD, were interviewed. RESULTS: The most common symptoms and signs
associated with an AE were difficulty breathing (84%), fatigue (81%), cold
symptoms (59%), changes in sputum colour (53%) or amount (47%), and cough (44%).
The main precipitants identified were environmental triggers (47%), infective
agents (31%), excessive activities (25%), emotional factors (16%) and changes in
medications (9%). Strategies for dyspnea relief included increasing medications
(72%), resting (56%), avoiding exposure to environmental triggers (41%) and
performing breathing exercises (31%). Patients supported the use of an AP and
recommended that it be individualized for symptoms and triggers, and that it
should also include strategies for addressing anxiety and depression. HCPs also
supported the use of an individualized AP and recommended that it be regularly
revisited, depending on the patient's disease severity. CONCLUSIONS: Patients'
experiences with AEs do not always conform to a standard medical definition.
Therefore, an understanding of their experience is of value in the design of an
individualized AP. HCPs support the use of an AP that emphasizes self-management
of exacerbations as well as general COPD management.
PMID- 17036090
TI - Surgical management of acute necrotizing lung infections.
AB - BACKGROUND: Surgical resection for acute necrotizing lung infections is not
widely accepted due to unclear indications and high risk. OBJECTIVE: To review
results of resection in the setting of acute necrotizing lung infections.
METHODS: A retrospective review of patients who underwent parenchymal resection
between January 1, 2000, and January 1, 2006, for management of necrotizing
pneumonia or lung gangrene. RESULTS: Thirty-five patients underwent resection for
lung necrosis. At the time of consultation, all patients presented with pulmonary
sepsis, and also had the following: empyema (n = 17), hemoptysis (n = 5), air
leak (n = 7), septic shock requiring pressors (n = 8) and inability to oxygenate
adequately (n = 7). Twenty-four patients were ventilated preoperatively. Eleven
patients had frank lobar gangrene, and the other patients had combinations of
necrotizing pneumonia and abscesses. In 10 patients, preresection procedures were
performed, including percutaneous drainage of an abscess (n = 4), thoracoscopic
decortication (n = 4) and open decortication (n = 2). Procedures included
pneumonectomy (n = 4), lobectomy (n = 18), segmentectomy (n = 2), wedge resection
(n = 4) and debridement (n = 7). There were three (8.5%) postoperative deaths-
two due to multiple organ failure and one due to anoxic brain injury. All
patients not ventilated preoperatively were weaned from ventilatory support
within three days. Of those ventilated preoperatively, three died, while four
remained chronically ventilator dependent. CONCLUSIONS: Surgical resection for
necrotizing lung infections is a reasonable option in patients with persistent
sepsis who are failing medical therapy. Ventilated patients have a worse
prognosis but can still be candidates for resection. Patients who are
hemodynamically unstable appear to have better outcomes if they can be stabilized
before resection.
PMID- 17036091
TI - Rare lung diseases I--Lymphangioleiomyomatosis.
AB - The present article is the first in a series that will review selected rare lung
diseases. The objective of this series is to promote a greater understanding and
awareness of these unusual conditions among respirologists. Each article will
begin with a case that serves as a focal point for a discussion of the
pathophysiology and management of the particular condition. The first article is
on lymphangioleiomyomatosis (LAM); subsequent articles will focus on pulmonary
alveolar proteinosis, alpha-1-antitrypsin deficiency and primary ciliary
dyskinesia. LAM is a rare, progressive and (without intervention) often fatal
interstitial lung disease that predominantly affects women of childbearing age.
LAM is characterized by progressive interstitial infiltration of the lung by
smooth muscle cells, resulting in diffuse cystic changes of the lung parenchyma.
The molecular basis of this disorder has been delineated over the past five years
and LAM is now known to be a consequence of mutations in the tuberous sclerosis
genes. This knowledge, combined with advances in our understanding of the
signalling pathways regulated by these genes, has given rise to potential
molecular therapies that hold great promise for treating this devastating
disease.
PMID- 17036092
TI - Recurrent respiratory papillomatosis causing chronic stridor and delayed speech
in an 18-month-old boy.
AB - Recurrent respiratory papillomatosis is a relatively uncommon disease that
presents clinically with symptoms ranging from hoarseness to severe dyspnea.
Human papilloma virus types 6 and 11 are important in the etiology of papillomas
and are most probably transmitted from mother to child during birth. Although
spontaneous remission is frequent, pulmonary spread and/or malignant
transformation resulting in death has been reported. CO2 laser evaporation of
papillomas and adjuvant drug therapy using lymphoblastoid interferon-alpha are
the most common treatments. However, several other treatments have been tried,
with varying success. In the present report, a case of laryngeal papillomatosis
presenting with chronic stridor and delayed speech is described.
PMID- 17036093
TI - An unusual pulmonary condition presenting following trauma.
AB - An 18-year-old man presented to the emergency department following an assault. He
complained of left-sided pleuritic chest pain and difficulty breathing. Clinical
examination revealed reduced air entry and coarse crepitations at the left lung
base. A chest x-ray showed a large opacity at the left lung base that contained
multiple cystic areas with air-fluid levels. Due to the history of trauma, a
provisional diagnosis of a ruptured hemidiaphragm with small bowel herniation was
made. Further imaging, including ultrasound, spiral computed tomography and
magnetic resonance angiography, showed an aberrant vessel supplying the opacity
and drainage into the pulmonary venous system. A diagnosis of a bronchopulmonary
sequestration (intralobar type) was made. The differential diagnosis of the
radiographic appearance is also discussed.
PMID- 17036094
TI - Canadian Thoracic Society guidelines: diagnosis and treatment of sleep disordered
breathing in adults.
PMID- 17036095
TI - The perils of omission.
PMID- 17036096
TI - Canadian guidelines for training in adult perioperative transesophageal
echocardiography. Recommendations of the Cardiovascular Section of the Canadian
Anesthesiologists' Society and the Canadian Society of Echocardiography.
AB - PURPOSE: To establish Canadian guidelines for training in adult perioperative
transesophageal echocardiography (TEE). METHODS: Guidelines were established by
the Canadian Perioperative Echocardiography Group with the support of the
cardiovascular section of the Canadian Anesthesiologists' Society in conjunction
with the Canadian Society of Echocardiography. Guidelines for training in
echocardiography by the American Society of Echocardiography, the American
College of Cardiology and the Society of Cardiovascular Anesthesiologists were
reviewed, modified and expanded to produce the 2003 Quebec expert consensus for
training in perioperative echocardiography. The Quebec expert consensus and the
2005 guidelines for the provision of echocardiography in Canada formed the basis
of the Canadian training guidelines in adult perioperative TEE. RESULTS: Basic,
advanced and director levels of expertise were identified. The total number of
echocardiographic examinations to achieve each level of expertise remains
unchanged from the 2002 American Society of Echocardiography and the Society of
Cardiovascular Anesthesiologists guidelines. The increased proportion of
examinations personally performed at basic and advanced levels, as well as the
level of autonomy at the basic level suggested by the Quebec expert consensus are
retained. These examinations may be performed in a perioperative setting and are
not limited to intraoperative TEE. Training 'on-the-job', the role of the
perioperative TEE examination, the requirements for maintenance of competence and
the duration of training are also discussed for each level of training. The
components of a TEE report and comprehensive TEE examination are also outlined.
CONCLUSION: The Canadian guidelines for training in adult perioperative TEE
reflect the unique Canadian practice profile in perioperative TEE and address the
training requirements to obtain expertise in this field.
PMID- 17036097
TI - Treating the right patient at the right time: Access to echocardiography in
Canada.
AB - The Canadian Cardiovascular Society is the national professional society for
cardiovascular specialists and researchers in Canada. In the spring of 2004, the
Canadian Cardiovascular Society Council formed the Access to Care Working Group
('Working Group') to use the best science and information available to establish
reasonable triage categories and safe wait times for access to common
cardiovascular procedures. The Working Group decided to publish a series of
commentaries to initiate a structured national discussion on this important
issue, and the present commentary proposes recommended wait times for access to
echocardiography. 'Emergent' echocardiograms should be performed within 24 h,
'urgent' within seven days and 'scheduled' (elective) within 30 days. A framework
for a solution-oriented approach to improve access is presented.
PMID- 17036100
TI - Morphological findings in 192 surgically excised native mitral valves.
AB - INTRODUCTION: Mitral valve disease (MVD) is a significant clinical problem that
is becoming more common in the 21st century. The pathogenesis of MVD seems to be
changing and is not well understood. PATIENTS AND METHODS: The present study
details the morphological findings in 192 native mitral valves excised over a one
year period at the Toronto General Hospital, Toronto, Ontario. The mean patient
age was 59.7+/-12.3 years at operation. RESULTS: There were 106 men (55.2%) and
86 women (44.8%) in the present study. The most frequent changes in the
surgically excised valvular leaflets were fibrosis (78.6%) and thickening
(66.2%). Fusion (32.3%) and calcification (25.2%) were common changes at the
commissures. Chordae tendineae most often showed evidence of thickening (47.9%)
and fibrosis (37.0%). In total, 110 valves showed mitral incompetence (57.3%), 72
showed mitral stenosis (37.5%), and 10 showed a combination of stenosis and
incompetence (5.2%). CONCLUSIONS: In the present series, MVD was most frequently
caused by postinflammatory (rheumatic) valve disease (RVD) (35.9%), followed by
myxomatous degeneration (33.3%). Patients with RVD were usually female (66.7%),
while those with myxomatous degeneration were more likely to be male (76.6%). RVD
remains a significant problem even though the incidence of acute rheumatic fever
with cardiac involvement has declined in Canada. This most likely reflects the
current sociodemographic composition of the referral population.
PMID- 17036099
TI - Timing, setting and incidence of cardiovascular complications in patients with
acute myocardial infarction submitted to primary percutaneous coronary
intervention.
AB - BACKGROUND: At the Istituto di Clinica Medica Generale e Cardiologia (Florence,
Italy), the widespread use of percutaneous coronary intervention (PCI) has
markedly changed the hospital course of patients with acute myocardial infarction
(AMI). These patients are typically transferred to the coronary care unit (CCU)
only after primary PCI, whereas during the thrombolytic era, patients were first
admitted to CCU before reperfusion. OBJECTIVES AND METHODS: The incidence, timing
and setting of complications from symptom onset to hospital discharge in 689
consecutive AMI patients undergoing PCI were evaluated. RESULTS: Ventricular
fibrillation occurred in 11% of patients, and most episodes (94.7%) occurred
before or during PCI. Of all patients, 6.3% developed complete atrioventricular
block (CAVB), and in 86.3% of these cases, the CAVB occurred before or during
PCI; in 94.5%, a CAVB resolution occurred in the catheterization laboratory (CL).
Thirty-one patients (4.5%) had impending shock on admission to the CL.
Cardiogenic shock developed in 2 9 patients (4.2%), mostly in the prehospital
phase or in the CL. Only four patients (less than 1%) developed cardiogenic shock
later during their hospital course. Similarly, circulatory and ventilatory
support, as well as temporary pacing and cardiac defibrillation, were used mostly
in the prehospital phase or in the CL. During the CCU stay, 45 patients (6.5%)
had hemorrhagic or vascular complications, and the incidence of post-PCI ischemia
and early reocclusion of the culprit vessel were low (2.1% and 0.6%,
respectively). Thus, cardiac complications usually associated with AMI were
observed mainly before hospital admission or in the CL during the reopening of
the target vessel. These complications were rarely observed after a successful
PCI. CONCLUSIONS: For AMI patients, the CL is not only the site of PCI, it is
also where most life-threatening cardiac complications are observed and treated.
PMID- 17036098
TI - Efficacy and tolerability of ezetimibe 10 mg/day coadministered with statins in
patients with primary hypercholesterolemia who do not achieve target LDL-C while
on statin monotherapy: A Canadian, multicentre, prospective study--the Ezetrol
Add-On Study.
AB - BACKGROUND: For patients who have above-target low-density lipoprotein
cholesterol (LDL-C) levels while on statin monotherapy, coadministration of a
cholesterol absorption inhibitor with the statin may decrease serum LDL-C levels
and improve overall lipid profiles. OBJECTIVES: To assess the effectiveness and
safety of ezetimibe 10 mg/day coadministered with a statin in patients with
primary hypercholesterolemia who have higher than recommended LDL-C levels while
on statin monotherapy. METHODS: A six-week, prospective, multicentre study of
eligible patients who had above-target LDL-C levels while on monotherapy with any
statin, regardless of dose, for a minimum of four weeks. All patients were
treated for six weeks with 10 mg ezetimibe daily coadministered with their
current statins. RESULTS: A total of 1141 patients were screened, 953 (83.5%)
fulfilled the study inclusion criteria and 837 (87.8%) completed the study.
Reasons for withdrawal included: lost to follow-up (50 patients [5.2%]); protocol
violations (45 patients [4.7%]); adverse events (19 patients [2.0%]); and
withdrawal of consent (two patients [0.2%]). After six weeks of treatment,
statistically significant (P = 0.001) mean reductions were observed in LDL-C
(30.05%), total cholesterol (20.84%), triglycerides (10.16%), apolipoprotein B
(19.84%) and the total cholesterol to high-density lipoprotein cholesterol ratio
(19.88%). At six weeks, 674 patients (80.5%) achieved target LDL-C levels. Fifty
predominantly mild, nonserious adverse events related to ezetimibe were reported
by 32 patients (3.4%). Frequently reported adverse events included constipation
(n = 7 [0.7% of patients]), diarrhea (n = 4 [0.4%]) and dizziness (n = 4 [0.4%]).
CONCLUSION: Ezetimibe coadministered with statins is effective in reducing LDL-C
in patients who do not attain target LDL-C levels while on statin monotherapy.
PMID- 17036102
TI - Native anomalous left coronary artery from the pulmonary artery in an adult:
Evidence of impaired coronary flow reserve by rubidium-82 positron emission
tomography quantification.
PMID- 17036101
TI - Transient left ventricular dysfunction (tako-tsubo phenomenon): Findings and
potential pathophysiological mechanisms.
AB - Tako-tsubo-like left ventricular dysfunction phenomenon (TTP) is characterized by
transient left ventricular apical ballooning associated with symptoms,
electrocardiographic changes and minimal cardiac enzyme release in the absence of
coronary artery disease. Initially described in Japan, TTP occurs worldwide,
predominantly in women and frequently after emotional or physical stress.
Symptoms include anginal chest pain, dyspnea and syncope. Electrocardiographic ST
elevations may be present only for several hours, and are followed by negative T
waves that persist for months. Arterial hypertension is found in up to 76% of TTP
patients, hyperlipidemia in up to 57% and diabetes mellitus in up to 12%.
Potential pathophysiological mechanisms for TTP include catecholamine-induced
myocardial stunning or hyperkinesis of the basal left ventricular segments,
coronary vasospasm, plaque rupture, myocarditis and genetic factors. TTP patients
should be monitored similarly to myocardial infarction patients because organ
failure, cardiogenic shock, ventricular fibrillation or rupture may occur. Beta
blockers are indicated, whereas catecholamines and nitrates should be avoided.
The long-term prognosis is unknown.
PMID- 17036104
TI - Biaryl synthesis with control of axial chirality.
AB - Biaryls have been a persistent focus of interest for chemists since it was
recognised, more than 80 years ago, that they can manifest the axial chirality
that is inherent in structures consisting of intersecting dissymmetric planes. In
recent decades their importance has risen steeply as this structural motif proved
spectacularly successful in catalytic synthetic roles and was found to be
significant in the context of biological activity. As a consequence, synthetic
methods which allowed the construction of biaryls with axial stereocontrol have
become highly desirable, and this article traces the development of non
resolution approaches to biaryls with a chosen axial configuration.
PMID- 17036103
TI - Left main coronary artery thrombectomy and stenting using a paclitaxel-eluting
stent in the setting of acute myocardial infarction.
AB - A 41-year-old man was referred to the Montreal Heart Institute, Montreal, Quebec,
for primary angioplasty of an acute anterolateral wall myocardial infarction.
Coronary angiography revealed the culprit lesion to be a subtotal left main
coronary artery with Thrombolysis In Myocardial Infarction (TIMI) trial grade 1
flow associated with a filling defect compatible with an aggressive thrombotic
process. The use of rheolytic thrombectomy and a drug-eluting stent for this
distal left main target lesion are described.
PMID- 17036105
TI - Synthesis and anticancer activity studies of alpha-aminoalkylated conjugated
nitroalkenes.
AB - Novel alpha-aminoalkylated conjugated nitroalkenes which inhibit human cervical
cancer (HeLa) cell proliferation by binding to tubulin were synthesized by
imidazole/LiCl-mediated reaction of conjugated nitroalkenes with N-tosylimines.
PMID- 17036106
TI - First total synthesis of the 7-oxygenated carbazole alkaloids clauszoline-K, 3
formyl-7-hydroxycarbazole, clausine M, clausine N and the anti-HIV active
siamenol using a highly efficient palladium-catalyzed approach.
AB - Using a convergent palladium-catalyzed construction of the carbazole framework as
the key step we have achieved a short synthesis of the 7-oxygenated carbazole
alkaloids clauszoline-K, 3-formyl-7-hydroxycarbazole, clausine C (clauszoline-L),
clausine M, clausine N and the anti-HIV active siamenol.
PMID- 17036107
TI - Two-directional synthesis and stereochemical assignment toward a C2 symmetric
oxasqualenoid (+)-intricatetraol.
AB - The asymmetric synthesis of tetraol (+)-3, a degradation product derived from a
C2 symmetric oxasqualenoid intricatetraol 1, has been achieved through the two
directional synthesis starting from diol 7, realizing the further additional
assignment of the incomplete stereostructure of 1, the stereochemistry of which
is difficult to determine otherwise.
PMID- 17036108
TI - Silenes in organic synthesis: a short synthesis of prelactone B.
AB - A sequence involving dihydroxylation and acid induced fragmentation of silene
generated silacyclohexenes represents the key step in a concise synthetic route
to beta-hydroxy-delta-lactones.
PMID- 17036109
TI - First synthesis of 1,2,3-triazolo-linked (1,6)-alpha-D-oligomannoses
(triazolomannoses) by iterative Cu(I)-catalyzed alkyne-azide cycloaddition.
AB - The iterative copper(I)-catalyzed cycloaddition (rt or microwave) between an
ethynyl alpha-C-mannoside and alkyl 6-azido-alpha-C-mannoside derivatives was
suited to the (1,6)-ligation between alpha-D-mannose units through 1,4
disubstituted triazole bridges, thus resulting in the formation of linear
oligomers (80-90% yield) with alternating triazole and mannose fragments up to a
triazolo-pentamannose derivative.
PMID- 17036110
TI - Synthesis of bisindolylmaleimides related to GF109203x and their efficient
conversion to the bioactive indolocarbazoles.
AB - From a structure-activity relationship perspective, the new indolocarbazoles 11
and 12 have been synthesized and evaluated biologically as novel Chk1 inhibitors.
Compounds 11 and 12 were synthesized in high yield from indole via
bisindolylmaleimides 18 and 24.
PMID- 17036111
TI - Rhodium-catalysed addition of organotrialkoxysilanes to alpha-substituted acrylic
esters.
AB - The cationic rhodium complex [Rh(cod)2][BF4] effectively catalyses the 1,4
addition of organotrialkoxysilanes to alpha-substituted acrylic esters. The
reactions are promoted by heating in an oil-bath or more conveniently in a
microwave reactor allowing rapid access to a useful range of functionalised
products including 2-alkyl succinates and alpha-amino acid derivatives.
PMID- 17036112
TI - Reproducibility and transferability of topological data: experimental charge
density study of two modifications of L-alanyl-L-tyrosyl-L-alanine.
AB - Two crystalline modifications of the tripeptide L-Ala-L-Tyr-L-Ala, which have
different solvent molecules in the crystal structure (water and ethanol for
modifications 1 and 2), were the subject of experimental charge density studies
based on high resolution X-ray data collected at ultra-low temperatures of 9 K
(1) and 20 K (2), respectively. The molecular structures and the intermolecular
interactions were found to be rather similar in the two crystal lattices, so that
this study allowed the reproducibility of the charge density of a given molecule
in different (but widely comparable) crystalline environments to be examined.
With respect to bond topological and atomic properties, the agreement between the
two modifications of the title tripeptide was in the same range as found from the
comparison with the previously reported results of tri-L-alanine. It follows that
the reproducibility and transferability of quantitative topological data are
comparable and that within the accuracy of experimental charge density work the
replacement of the central amino acid residue L-Ala by L-Tyr has no significant
influence, neither on bond nor on the atomic properties of the oligopeptide main
chain. Intermolecular interactions in the form of hydrogen bonds were
characterized quantitatively and qualitatively by topological criteria and by
mapping the charge density distribution on the Hirshfeld surface.
PMID- 17036113
TI - The design and synthesis of 9-phenylcyclohepta[d]pyrimidine-2,4-dione derivatives
as potent non-nucleoside inhibitors of HIV reverse transcriptase.
AB - Novel compounds, which can be considered as conformationally restricted analogues
of MKC-442, have been synthesized and tested as inhibitors of the reverse
transcriptase of human immunodeficiency virus type-1 (HIV-1). Reaction of urea
with a beta-ketoester furnished 6,7,8,9-tetrahydro-9-phenyl-1H
cyclohepta[d]pyrimidine-2,4-(3H,5H)-dione (6a) and 6,7,8,9-tetrahydro-9-p-tolyl
1H-cyclohepta[d]pyrimidine-2,4-(3H,5H)-dione (6b) which were then alkylated at
the N-1 position with chloromethyl ether, allyl bromide and benzyl bromide to
afford the target compounds 7a-b, 8a-b, 9 and 10, respectively. The seven
membered, annelated compounds have a relatively rigid structures and can lock the
orientation of the aromatic ring. Chemical modification at N-1 of the pyrinidine
ring and the 9-phenyl ring was attempted, with the aim of improving the
antiretroviral activity. In particular, replacement of the aliphatic group with
the phenyl moiety at the terminus of N-1 side chain can enhance the activity. The
most active compounds showed activity in the low micromolar range with IC50
values comparable to that of nevirapine. The biological activity results are in
accordance with the docking results.
PMID- 17036115
TI - Artificial aldolases from peptide dendrimer combinatorial libraries.
AB - Peptide dendrimers were investigated as synthetic models for aldolase enzymes.
Combinatorial libraries were prepared with aldolase active residues such as
lysine and proline placed at the dendrimer core or near the surface. On-bead
selection for aldolase activity was carried out using the dye-labelled 1,3
diketone 1a, suitable for covalent trapping of enamine-reactive side-chains, and
the fluorogenic enolization probe 6. Aldolase dendrimers catalyzed the aldol
reaction of acetone, dihydroxyacetone and cyclohexanone with nitrobenzaldehyde.
Much like enzymes, the dendrimers exhibited strong aldolase activity in aqueous
medium, but were also active in organic solvent. Dendrimer-catalyzed aldol
reactions reached complete conversion in 3 h at 25 degrees C with 1 mol% catalyst
and gave aldol products with up to 65% ee. A positive dendritic effect in
catalysis was observed with both lysine and proline based aldolase dendrimer
catalysts.
PMID- 17036114
TI - Synthesis and optimization of peptidomimetics as HIV entry inhibitors against the
receptor protein CD4 using STD NMR and ligand docking.
AB - We recently described the design and synthesis of a novel CD4 binding
peptidomimetic as a potential HIV entry inhibitor with a KD value of
approximately 35 microM and a high proteolytic stability [A. T. Neffe and B.
Meyer, Angew. Chem., Int. Ed., 2004, 43, 2937-2940]. Based on saturation transfer
difference (STD) NMR analyses and docking studies of peptidomimetics we now
report the rational design, synthesis, and binding properties of 11 compounds
with improved binding affinity. Surface plasmon resonance (SPR) resulted in a KD
= 10 microM for the best peptidomimetic XI, whose binding affinity is confirmed
by STD NMR (KD = 9 microM). The STD NMR determined binding epitope of the ligand
indicates a very similar binding mode as that of the lead structure. The binding
studies provide structure activity relationships and demonstrate the utility of
this approach.
PMID- 17036116
TI - Reactions of indoles with nitrogen dioxide and nitrous acid in an aprotic
solvent.
AB - The reaction of 2-phenyl- and 1-methyl-2-phenylindole with nitrogen dioxide or
with nitrous acid (NaNO2-CH3COOH) in benzene leads mainly to the formation of the
isonitroso and 3-nitroso indole derivatives, respectively. When reacted with
nitrous acid, 1-methyl-2-phenylindole gives also the corresponding azo-bis-indole
in good yields. The reaction of indole with nitrogen dioxide leads to 2-(indol-3
yl)-3H-indol-3-one as the main product together with small amounts of 2-(indol-3
yl)-3H-indol-3-oxime; whereas the major product obtained when the same indole is
reacted with nitrous acid is represented by 2-(indol-3-yl)-3H-indol-3-oxime. The
reaction of 3-alkyl substituted indoles with nitrogen dioxide is rather complex
and results in the formation of different nitro indoles, whereas nitrosation is
observed when nitrous acid is used. Crystal structures of 2-(indol-3-yl)-3H-indol
3-one and of 4-nitro-N-acetyltryptamine have been determined by X-ray analysis.
PMID- 17036117
TI - A practical synthetic route to functionalized THBCs and oxygenated analogues via
intramolecular Friedel-Crafts reactions.
AB - A practical catalytic approach to the synthesis of 4-substituted 1,2,3,4
tetrahydro-beta-carbolines (THBCs, 1) and 1,2,3,9-tetrahydropyrano[3,4-b]indoles
(2) via InBr3-catalyzed intramolecular Friedel-Crafts (F-C) cyclization is
described. The use of cross-metathesis reaction represents a direct route to the
cyclization precursors and the use of InBr3 (5 mol%) allowed polycyclic indole
compounds to be isolated in high yields under mild reaction conditions (rt, DCM,
minutes). Finally, efforts toward the development of a stereocontrolled version
of the present cyclization are presented, highlighting [salenAlCl] and bimetallic
[(salenAlCl)2-InBr3] system as promising chiral Lewis acids (ee up to 60%).
PMID- 17036118
TI - Synthesis and structure of bifunctional N-alkylbenzimidazole phenylboronate
derivatives.
AB - N-Methyl and N-n-butyl-2-(2-boronophenyl)benzimidazoles are accessed from the
corresponding mono-N-alkyl-ortho-phenylenediamines, either using a polyphosphoric
acid-mediated cyclisation with ortho-bromobenzoic acid, or preferably using an
Oxone-mediated cyclisation of the corresponding aldehyde, followed by a lithium
exchange and borylation sequence. The resulting boronic acids show unusual
physical and chemical properties, as shown by 11B NMR and X-ray crystallography.
PMID- 17036119
TI - Synthesis of 1-beta-O-acyl glucuronides of diclofenac, mefenamic acid and (S)
naproxen by the chemo-selective enzymatic removal of protecting groups from the
corresponding methyl acetyl derivatives.
AB - Using a straightforward chemo-enzymatic procedure, 1-beta-O-acyl glucuronides of
three non-steroidal anti-inflammatory drugs, diclofenac (DF) 5, mefenamic acid
(MF) 6 and (S)-naproxen (NP) 7, were prepared. Caesium salts of these carboxylic
acid drugs reacted with commercially available methyl 2,3,4-tri-O-acetyl-1-bromo
1-deoxy-alpha-D-glucopyranuronate 4 to give exclusively the corresponding 1-beta
O-acyl glucuronides 8-10 in moderate yields. The protecting acetyl (for -OH
group) and methyl ester (for -CO2H group) groups of each sugar moiety were easily
removed to provide the corresponding free 1-beta-O-acyl glucuronides 1-3 in high
yields. Deprotection was achieved through effective enzyme-catalysed chemo
selective hydrolyses of the acetyl groups using lipase AS Amano (LAS), and of the
methyl ester group using esterase from porcine liver (PLE).
PMID- 17036121
TI - Asymmetric transfer hydrogenation catalysed by hydrophobic dendritic DACH-rhodium
complex in water.
AB - Hydrophobic Frechet-type dendritic chiral 1,2-diaminocyclohexane-Rh(III)
complexes have been applied in the asymmetric transfer hydrogenation of ketones
in water using HCOONa as hydrogen source. The catalysts were found to be finely
dissolved in the liquid substrates in the aqueous mixture and exhibited high
catalytic activity and enantioselectivity (52-97% ee). The catalytic loading
could be decreased to 0.01 mol% and good conversion was still obtained with
excellent enantioselectivity. Moreover, the catalyst could be easily precipitated
from the mixture by adding hexane and reused several times without affecting the
high enantioselectivity.
PMID- 17036122
TI - Synthesis of the C1-C16 fragment of ionomycin using a neutral (eta3-allyl)iron
complex.
AB - Key steps in the synthesis of the C1-C16 polyketide fragment of ionomycin were
the nucleophilic addition of an organocuprate to a neutral (eta3-allyl)iron
complex and the construction of a beta-diketone moiety by the Rh-catalysed
rearrangement of an alpha-diazo-beta-hydroxyketone.
PMID- 17036120
TI - Total synthesis of enantiopure 1,3-dimethylpyranonaphthoquinones including
ventiloquinones E, G, L and eleutherin.
AB - A new synthetic approach to enantiopure pyranonaphthoquinones is described. (S)
Mellein 10, prepared in 6 steps from (S)-propylene oxide 16, is converted
stereospecifically to the (1R,3S)-dimethylpyran 15. The pyran 15 is then
converted to the benzoquinone 14, which undergoes regiospecific Diels-Alder
reactions with a variety of oxygenated butadienes to give pyranonaphthoquinones
including ventiloquinones E, G, L, eleutherin and ent-deoxyquinone A.
PMID- 17036123
TI - Synthesis and G-quadruplex binding studies of new 4-N-methylpyridinium
porphyrins.
AB - A series of cationic porphyrins carrying 1-3 meso-N-pyridinium groups has been
synthesised, and their binding to G-quadruplex DNA has been explored by surface
plasmon resonance (SPR) and circular dichroism spectroscopy. Two trans
substituents appear to be sufficient for tight binding; preferential binding to
the anti-parallel intramolecular human telomeric DNA was observed for the A2trans
and A3 porphyrins. The A2trans is able to induce the formation of an anti
parallel G-quadruplex in a K+ free solution, mimicking the effect of a molecular
chaperone.
PMID- 17036124
TI - Dioxygenase-catalysed oxidation of disubstituted benzene substrates: benzylic
monohydroxylation versus aryl cis-dihydroxylation and the meta effect.
AB - Biotransformations of a series of ortho-, meta- and para-substituted ethylbenzene
and propylbenzene substrates have been carried out, using Pseudomonas putida UV4,
a source of toluene dioxygenase (TDO). The ortho- and para-substituted
alkylbenzene substrates yielded, exclusively, the corresponding enantiopure cis
dihydrodiols of the same absolute configuration. However, the meta isomers,
generally, gave benzylic alcohol bioproducts, in addition to the cis-dihydrodiols
(the meta effect). The benzylic alcohols were of identical (R) absolute
configuration but enantiomeric excess values were variable. The similar (2R)
absolute configurations of the cis-dihydrodiols are consistent with both the
ethyl and propyl groups having dominant stereodirecting effects over the other
substituents. The model used earlier, to predict the regio- and stereo-chemistry
of cis-dihydrodiol bioproducts derived from substituted benzene substrates has
been refined, to take account of non-symmetric substituents like ethyl or propyl
groups. The formation of benzylic hydroxylation products, from meta-substituted
benzene substrates, without further cis-dihydroxylation to yield triols provides
a further example of the meta effect during toluene dioxygenase-catalysed
oxidations.
PMID- 17036125
TI - New 64Cu PET imaging agents for personalised medicine and drug development using
the hexa-aza cage, SarAr.
AB - The success of positron emission tomography (PET) in personalised medicine and
drug development requires radioisotopes that provide high quality images and
flexible chemistry for a broad application. 64Cu is arguably one of the most
suitable PET isotopes for imaging with the evolving target agents, but there are
not many appropriate chelating agents for 64Cu and this has limited its wider
application. The bi-functional chelator, SarAr is known to bind 64Cu2+
quantitatively (i.e. one metal per ligand present) and rapidly (<2 min) at 10(-6)
M over a range of pH (4-9). In this paper the conjugation of SarAr to the whole
and fragmented antibody is described. Conjugation of the SarAr to the protein
does not impair its coordination of the 64Cu. It complexes the 64Cu2+ rapidly,
quantitatively and essentially irreversibly at pH 5. Animal studies show that the
64Cu-SarAr-immunoconjugates maintain their specificity for the target and are
stable in vivo. Also, SarAr is a platform technology, is easy to use in a kit
formulation and is readily adaptable for the wider application in 64Cu PET
imaging.
PMID- 17036126
TI - Phenol quaternary ammonium derivatives: charge and linker effect on their DNA
photo-inducible cross-linking abilities.
AB - We report here that phenol derivatives with two and four quaternary ammoniums
were synthesized and their abilities to bind and cross-link DNA were
investigated. Thermal denaturizing studies indicated that derivatives possess
similar DNA binding abilities and gel electrophoresis revealed that more charges
(series B) and electronic donation substitute linkers (like -S-) dramatically
increase the DNA cross-linking abilities.
PMID- 17036127
TI - Editorial: DNA-based nanoarchitectures and nanomachines.
AB - The emerging area of DNA-based architectures and machines promises exciting
opportunities and will impact on the future of DNA structures in
nanobiotechnology.
PMID- 17036128
TI - DNA nanomachines and nanostructures involving quadruplexes.
AB - DNA is an attractive component for molecular recognition, because of its self
assembly properties. Its three-dimensional structure can differ markedly from the
classical double helix. For example, DNA or RNA strands carrying guanine or
cytosine stretches associate into four-stranded structures called G-quadruplexes
or i-DNA, respectively. Since 2002, several groups have described nanomachines
that take advantage of this structural polymorphism. We first introduce the
unusual structures that are involved in these devices (i.e., i-DNA and G
quadruplexes) and then describe the opening and closing steps that allow cycling.
A quadruplex-duplex molecular machine is then presented in detail, together with
the rules that govern its formation, its opening/closing kinetics and the various
technical and physico-chemical parameters that play a role in the efficiency of
this device. Finally, we review the few examples of nanostructures that involve
quadruplexes.
PMID- 17036129
TI - DNA-based machines.
AB - Nucleic acids include substantial information in their base sequence and their
hybridization-complexation motifs. Recent research efforts attempt to utilize
this biomolecular information to develop DNA nanostructures exhibiting machine
like functions. DNA nano-assemblies revealing tweezers, motor, and walker
activities exemplify a few such machines. The DNA-based machines provide new
components that act as sensitive sensors, transporters, or drug delivery systems.
PMID- 17036130
TI - Combinatorial self-assembly of DNA nanostructures.
AB - Here we report a modular design of self-assembly of DNA nanostructures in a
combinatorial approach; a square with approximately 25 nm cavity dimension, a
chair with approximately 80 nm in height and a line with approximately 100 nm in
length are formed through combinations of four cross-shaped DNA tiles which are
kept constant and six variable linker tiles.
PMID- 17036131
TI - Preparation of branched structures with long DNA duplex arms.
AB - Branched structures with long DNA duplex arms have been constructed through
biotin-streptavidin binding and characterized by gel electrophoresis and atomic
force microscopy (AFM) imaging.
PMID- 17036132
TI - Molecular design of novel non-planar heteropolycyclic fluorophores with bulky
substituents: convenient synthesis and solid-state fluorescence characterization.
AB - Novel indeno[1,2-b]benzo[4,5-e]pyran-11-one-type fluorophores exhibiting intense
solid-state fluorescence were conveniently synthesized and the relation between
their solid-state photophysical properties and the X-ray crystal structures were
investigated, which demonstrates that non-planar structures with sterical
hindered substituents prevent the fluorophores from forming short pi-pi contacts
causing fluorescence quenching in the solid state.
PMID- 17036133
TI - New ortho-quinone methide formation: application to three-component coupling of
isocyanides, aldehydes and phenols.
AB - Herein, we wish to report a new three-component formation of heterocyclic
scaffolds based on a one-pot process from simple phenols. The key step of this
procedure involves an ortho-quinone methide formation from Mannich adducts under
alkylative conditions. The transient o-quinone methide has been trapped in situ
with indole and diketone using lithium perchlorate as catalyst. The interest of
this procedure has been furthermore demonstrated by a new three-component
aminobenzofuran formation from phenols, aldehydes and isocyanides.
PMID- 17036134
TI - Double cohesion in structural DNA nanotechnology.
AB - Double cohesion has proved to be a useful tool to assemble robust 2D arrays of
large tiles. Here we present a variety of examples showing the utility of this
approach. We apply this principle to the 3 types of 2D lattice sections of arrays
whose individual tiles are inherently 3 dimensional, because they contain three
vectors that span 3-space. This application includes motifs which are based on
the tensegrity triangle, the six-helix bundle motif and on three skewed triple
crossover molecules. All of these designs have the potential to form 3
dimensional structures if all three directions of propagation are allowed. If one
direction is blunted, 2D arrays form, and all 3 combinations are presented here.
In addition, a large parallelogram array that was not attainable previously using
single duplex cohesion was also constructed using double cohesion. For
comparison, arrays which use another type of double cohesion, double paranemic
(PX) cohesion are also presented. Double cohesion of sticky ends proved to be the
more effective tool to assemble large motifs into arrays.
PMID- 17036136
TI - Characterization and modulation of the hierarchical self-assembly of
nanostructured DNA tiles into supramolecular polymers.
AB - We present a set of DNA supramolecular architectures based on the polymerization
of discrete DNA tiles having the shape of parallelograms and designed to have a
one-dimensional inter-tile connectivity. Tiles bind to each other with two
connections, which have different thermal stabilities. We discuss how this
difference in stability implies that the same monomeric tile can yield
supramolecular polymers of different shapes just by changing the polymerization
conditions. We show how this system reacts to external stimuli by interconverting
between some of its possible states. Concurrently, we show how performing the
polymerization on a surface can influence its outcome.
PMID- 17036135
TI - Single-chain antibodies against DNA aptamers for use as adapter molecules on DNA
tile arrays in nanoscale materials organization.
AB - Complex DNA nanostructures have been developed as structural components for the
construction of nanoscale objects. Recent advances have enabled self-assembly of
organized DNA nanolattices and their use in patterning functional bio
macromolecules and other nanomaterials. Adapter molecules that bind specifically
to both DNA lattices and nanomaterials would be useful components in a molecular
construction kit for patterned nanodevices. Herein we describe the selection from
phage display libraries of single-chain antibodies (scFv) for binding to a
specific DNA aptamer and their development as adapter molecules for nanoscale
construction. We demonstrate the decoration of various DNA tile structures with
aptamers and show binding of the selected single-chain antibody as well as the
self-assembly of mixed DNA-protein biomolecular lattices.
PMID- 17036137
TI - Design of asymmetric DNAzymes for dynamic control of nanoparticle aggregation
states in response to chemical stimuli.
AB - Dynamic control of nanomaterial assembly states in response to chemical stimuli
is critical in making multi-component materials with interesting properties.
Previous work has shown that a Pb2+-specific DNAzyme allowed dynamic control of
gold nanoparticle aggregation states in response to Pb2+, and the resulting color
change from blue aggregates to red dispersed particles can be used as a
convenient way of sensing Pb2+. However, a small piece of DNA (called invasive
DNA) and low ionic strength (approximately 30 mM) were required for the process,
limiting the scope of application in assembly and sensing. To overcome this
limitation, a series of asymmetric DNAzymes, in which one of the two substrate
binding regions is longer than the other, has been developed. With such a system,
we demonstrated Pb2+-induced disassembly of gold nanoparticle aggregates and
corresponding color change at room temperature without the need for invasive DNA,
while also making the system more tolerant to ionic strength (33-100 mM). The
optimal lengths of the long and short arms were determined to be 14 and 5 base
pairs, respectively. In nanoparticle aggregates, the activity of the DNAzyme
increased with decreasing ionic strength of the reaction buffer. This simpler and
more versatile system allows even better dynamic control of nanoparticle
aggregation states in response to chemical stimuli such as Pb2+, and can be used
in a wider range of applications for colorimetric sensing of metal ions.
PMID- 17036138
TI - Synthesis of an elongated linear oligo(phenylene ethynylene)-based building block
for application in DNA-programmed assembly.
AB - The synthesis of an elongated linear oligonucleotide-functionalised module (ELOM)
is described. The ELOM structure is based on an oligo(phenylene ethynylene)
backbone substituted with two decyloxy groups. The two termini constitute two
salicylaldehyde moieties acting as chemical cross-linkers. Before incorporation
into an oligonucleotide sequence the organic part of the module, the elongated
linear module (ELM), is functionalised with a dimethoxytrityl group and a
phosphoramidite group. This enables incorporation into the middle of 30-mer
oligonucleotide sequences by automated DNA synthesis. The obtained ELOMs were
characterised by polyacrylamide gel electrophoresis and MALDI-TOF mass
spectrometry. In analogy with previously reported LOM and TOM structures the
coupling reactions of the ELOM modules were tested.
PMID- 17036139
TI - Electrical manipulation of oligonucleotides grafted to charged surfaces.
AB - The electrical manipulation of short DNA molecules on surfaces offers novel
functionalities with fascinating possibilities in the field of bio-interfaces.
Here we present systematic investigations of the electrical interactions which
govern the structure of oligonucleotides on charged gold surfaces. Successively,
we address influences of the applied field strength, the role of DC electrode
potentials, in particular for polycrystalline surfaces, as well as screening
effects of the surrounding electrolyte solution. Data obtained for single and
double stranded DNA exhibit differences which can be attributed to the dissimilar
flexibility of the different molecular conformations. A comparison of the
experimental results with a basic model shows how the alignment of the molecules
adjusts according to a balance between electrically induced ordering and
stochastic thermal motions. The presented conclusions are expected to be of
general relevance for the behaviour of polyelectrolytes exposed to localized
electric fields at interfaces.
PMID- 17036140
TI - Non-enzymatic reduction of quinone methides during oxidative coupling of
monolignols: implications for the origin of benzyl structures in lignins.
AB - Lignin is believed to be synthesized by oxidative coupling of 4
hydroxyphenylpropanoids. In native lignin there are some types of reduced
structures that cannot be explained solely by oxidative coupling. In the present
work we showed via biomimetic model experiments that nicotinamide adenine
dinucleotide (NADH), in an uncatalyzed process, reduced a beta-aryl ether quinone
methide to its benzyl derivative. A number of other biologically significant
reductants, including the enzyme cellobiose dehydrogenase, failed to produce the
reduced structures. Synthetic dehydrogenation polymers of coniferyl alcohol
synthesized (under oxidative conditions) in the presence of the reductant NADH
produced the same kind of reduced structures as in the model experiment,
demonstrating that oxidative and reductive processes can occur in the same
environment, and that reduction of the in situ-generated quinone methides was
sufficiently competitive with water addition. In situ reduction of beta-beta
quinone methides was not achieved in this study. The origin of racemic benzyl
structures in lignins therefore remains unknown, but the potential for simple
chemical reduction is demonstrated here.
PMID- 17036141
TI - Homogeneous enzymatic reactions in ionic liquids with poly(ethylene glycol)
modified subtilisin.
AB - Subtilisin Carlsberg was covalently modified with comb-shaped poly(ethylene
glycol) (PM13). PM13-modified subtilisin (PM13-Sub) was readily solubilized in
three different ionic liquids (ILs), i.e., [Emim][Tf2N], [C2OC1mim][Tf2N] and
[C2OHmim][Tf2N]. Analysis of homogeneous enzymatic reactions in the ILs revealed
that PM13-Sub exhibited excellent catalytic performance while the native enzyme
suspended in ILs showed no activity. Hydrophobicity of ILs slightly affected
enzyme activity, and the relatively hydrophobic IL [Emim][Tf2N] was the preferred
medium for enzymatic reactions, similar to enzymatic reactions in conventional
organic solvents. Enzyme activity was much higher in [Emim][Tf2N] than in
conventional organic solvents, and excellent activity was associated with unique
properties of ILs such as hydrophobicity and high polarity. Furthermore, PM13-Sub
showed good stability in [Emim][Tf2N], and maintained 80% of its initial activity
after 60 h.
PMID- 17036142
TI - A combined molecular dynamics simulation and quantum chemical study on the
mechanism for activation of the OxyR transcription factor by hydrogen peroxide.
AB - Molecular dynamics (MD) simulations have been performed on the regulatory domain
of the Escherichia coli OxyR transcription factor for the different chemical
states along the mechanistic cycle for its activation by hydrogen peroxide.
Conformational analysis indicates that His198 and Arg220 catalytic residues can
be involved in the biochemical process of activation of OxyR. On the basis of the
simulation data, a detailed mechanism for the oxidation process is suggested in
which His198, in the presence of an arginine residue, functions as a unique acid
base catalyst in the successive oxidations of Cys199 and Cys208 by hydrogen
peroxide. This mechanistic proposal has been tested by density functional theory
(DFT-B3LYP) and ab initio (MP2) calculations on model systems. The two oxidations
are both identified as nucleophilic substitution reactions of SN2 type with
deprotonated cysteines functioning as nucleophiles. Both reactions have a
calculated free energy of activation close to 15 kcal mol-1, which is consistent
with the available experimental data on the kinetics of the activation process.
PMID- 17036143
TI - Synthesis of distamycin A polyamides targeting G-quadruplex DNA.
AB - A number of amide-linked oligopyrroles based on distamycin molecules have been
synthesized by solid-state methods, and their interactions with a human
intramolecular G-quadruplex have been measured by a melting procedure. Several of
these molecules show an enhanced ratio of quadruplex vs. duplex DNA binding
compared to distamycin itself, including one with a 2,5-disubstituted pyrrole
group. Quadruplex affinity increases with the number of pyrrole groups, and it is
suggested that this is consistent with a mixed groove/G-quartet stacking binding
mode.
PMID- 17036145
TI - Concise access to indolizidine and pyrroloazepine skeleta via intramolecular
Schmidt reactions of azido 1,3-diketones.
AB - Readily prepared 2-alkyl-2-azidopropylcycloalkyl-1,3-diones undergo
intramolecular Schmidt rearrangement with a range of hard Lewis acids, leading to
indolizidinediones and pyrroloazepinediones. Chiral aluminium-based Lewis acids
could also be used to mediate this symmetry-breaking transformation, but no
significant asymmetric induction was observed.
PMID- 17036144
TI - MAGfect: a novel liposome formulation for MRI labelling and visualization of
cells.
AB - Cellular entry of imaging probes, such as contrast agents for magnetic resonance
imaging (MRI), is a key requirement for many molecular imaging studies,
particularly imaging intracellular events and cell tracking. Here, we describe
the successful development and in vitro analysis of MAGfect, a novel liposome
formulation containing a lipidic gadolinium contrast agent for MRI, Gd-DOTA-Chol
, designed to enter and label cells. Liposome formulation and cell incubation
time were optimised for maximum cellular uptake of the imaging probe in a variety
of cell lines. MRI analysis of cells incubated with MAGfect showed them to be
highly MRI active. This formulation was examined further for cytotoxicity, cell
viability and mechanism of cell labelling. One of the key advantages of using
MAGfect as a labelling vehicle arises from its potential for additional
functions, such as concomitant drug or gene delivery and fluorescent labelling.
The gadolinium liposome was found to be an effective vehicle for transport of
plasmid DNA (pDNA) into cells and expression levels were comparable to the
commercial transfection agent Trojene.
PMID- 17036146
TI - Supramolecular complexes of spin-labelled cyclodextrins.
AB - EPR spectra of cyclodextrins labelled with TEMPO derivatives (SL-CDs) are
sensitive to complexation with large guest molecules. We used SL-CDs to explore
the behaviour of concentrated PEG/PPG solutions. The relationship between
rotational correlation times and solvent viscosity showed significant deviations
from the Debye-Stokes-Einstein equation, probably due to self-aggregation of
alkylene glycols in concentrated solutions. The data fit the fractional Debye
Stokes-Einstein equation well. We have also studied complexation of SL-CDs with
adamantane-functionalised DAB dendrimers. The strength of binding increases with
dendrimer generation; formation of supramolecular aggregates at high
concentrations was observed with the generation 3 dendrimer.
PMID- 17036147
TI - The different electronic natures displayed by the alkylthio groups in simple and
higher conjugated aniline systems.
AB - Systematic studies based on 1H NMR and 13C NMR indicated that the alkylthio group
behaves as a weak electron-withdrawing group in a simple aniline system like 2
butylthioaniline, while the same alkylthio group clearly acted as a resonance
electron-donating group in higher conjugated aniline trimer systems, like
butylthio-substituted PDA (mono-PDA) and dibutylthio-substituted PDA (2,6-diPDA).
The formation of 2,6-diPDA as the major byproduct during the preparation of mono
PDA from PDI and butane-1-thiol provided additional support for the resonance
electron donating nature of the butylthio group in these aniline trimer systems.
Furthermore, CV studies also clearly indicated that the redox potential E degrees
(vs. SCE) of the aniline trimer systems decreased with the increase in the number
of butylthio groups, further confirming the electron-donating nature of the
butylthio group in these higher conjugated trimer systems.
PMID- 17036148
TI - Discovery of aspoquinolones A-D, prenylated quinoline-2-one alkaloids from
Aspergillus nidulans, motivated by genome mining.
AB - Motivated by the observation that the Aspergillus nidulans genome bears multiple
anthranilic acid synthase gene copies, the fungal metabolome was reinvestigated
under various fermentation conditions, resulting in the discovery of novel
prenylated quinolin-2-one alkaloids, two of which bear unprecedented terpenoid
side chains.
PMID- 17036149
TI - A short enantioselective total synthesis of the phytotoxic lactone herbarumin
III.
AB - The phytotoxic lactone herbarumin III has been synthesized in 11% overall yield.
The approach applied uses Keck's asymmetric allylation and Sharpless epoxidation
to build the key fragment. Esterification with 5-hexenoic acid and a ring closing
metathesis was used to arrive at the target.
PMID- 17036150
TI - Metabolism of the crucifer phytoalexins wasalexin A and B in the plant pathogenic
fungus Leptosphaeria maculans.
AB - Wasalexins A and B are crucifer phytoalexins produced by two substantially
different plant species, a wild species abundant in the Canadian prairies and a
condiment plant widely cultivated in Japan. Interestingly, both plant species are
resistant to an economically important fungal plant pathogen, the blackleg fungus
[Leptosphaeria maculans (Desm.) Ces. et de Not., asexual stage Phoma lingam (Tode
ex Fr.) Desm.]. The transformation of wasalexins A and B in cultures of isolates
of L. maculans, an isolate highly virulent towards canola (BJ 125) and a less
common isolate which is virulent towards wasabi (Laird 2/Mayfair 2) was
investigated. It was established that both fungal isolates are able to
efficiently metabolize and detoxify wasalexins A and B through reduction in the
case of wasalexin A or through hydrolysis followed by reduction in the case of
wasalexin B. Moreover, a close structural analogue of wasalexins, which does not
occur naturally, was also found to be reduced in cultures of L. maculans. The
structures of the new metabolic products were elucidated using spectroscopic
methods and were confirmed by synthesis. Bioassays indicated that the
biotransformation of wasalexins is a detoxification process that may contribute
to the aggressive nature of these fungal isolates towards plants that produce
wasalexins.
PMID- 17036151
TI - Prevalence of respiratory viruses, including newly identified viruses, in
hospitalised children in Austria.
AB - The aim of this epidemiological study was to determine the prevalence of
respiratory viruses, including new viruses, in hospitalised children in Austria.
Two hundred fourteen nasopharyngeal samples from hospitalised children were
tested for the presence of viruses using cell culture and PCR and/or viral
antigen assays. The results revealed a parainfluenza virus 1 (PIV1) outbreak that
ended right before the onset of the influenza season, with nearly no overlapping,
moderate respiratory syncytial virus (RSV) activity, and only a few adenoviruses.
Human metapneumovirus (hMPV) was present in 14.5% of the total samples but was
detected in combination with other viruses in only five cases: with PIV1 in three
cases and with RSV in two cases. There were no cases of dual infection with hMPV
and flu or adenovirus. This suggests that hMPV alone is a leading cause of
hospitalisation in children under 1 year of age. Interestingly, hMPV, in contrast
to RSV, coincided with PIV1 but was absent during the community outbreak of the
flu. Samples were also tested for Mimiviridae, a group of newly described DNA
viruses that are similar to Legionella spp., replicate in water amoebae, and also
have been found in alveolar cells. However, mimivirus was detected neither in
respiratory samples nor in amoebae-containing water samples, indicating that this
particular type of virus is either not abundant or does not contribute to
paediatric respiratory illnesses.
PMID- 17036152
TI - Evaluation of Rapid U Legionella Plus Test, a new immunochromatographic assay for
detection of Legionella pneumophila serogroup 1 antigen in urine.
PMID- 17036154
TI - MR arthrography in calcific tendinitis of the shoulder: diagnostic performance
and pitfalls.
AB - The purpose was to assess the diagnostic performance of MR arthrography to
diagnose calcific tendinitis of the shoulder and to assess the reasons for
diagnostic errors. Standard MR arthrograms of 22 patients with calcific
tendinitis and 61 controls were retrospectively analyzed by two independent and
blinded radiologists. All cases were consecutively collected from a database.
Conventional radiographs were available in all cases serving as gold standard.
The supraspinatus was involved in 16, the infraspinatus in four and the
subscapularis in two patients. All diagnostic errors were analyzed by two
additional readers. Reader 1 correctly detected 12 of the 22 shoulders with and
42 of the 61 shoulders without calcific tendinitis (sensitivity 0.55, specificity
0.66). The corresponding values for reader 2 were 13 of 22 and 40 of 61 cases
(sensitivity 0.59, specificity 0.69). Inter-rater agreement (kappa-value) was
0.42. Small size of the calcific deposits and isointensity compared to the
surrounding tissue were the most important reasons for false negative results.
Normal hypointense areas within the supraspinatus tendon substance and attachment
were the main reason for false positive results. In conclusion, MR arthrography
is insufficient in the diagnosis of calcific tendinitis. Normal hypointense parts
of the rotator cuff may mimic calcific deposits and calcifications may not be
detected when they are isointense compared to the rotator cuff. Therefore, MR
imaging should not be interpreted without corresponding radiographs.
PMID- 17036153
TI - Comparison of fMRI coregistration results between human experts and software
solutions in patients and healthy subjects.
AB - Functional magnetic resonance imaging (fMRI) performed by echo-planar imaging
(EPI) is often highly distorted, and it is therefore necessary to coregister the
functional to undistorted anatomical images, especially for clinical
applications. This pilot study provides an evaluation of human and automatic
coregistration results in the human motor cortex of normal and pathological
brains. Ten healthy right-handed subjects and ten right-handed patients performed
simple right hand movements during fMRI. A reference point chosen at a
characteristic anatomical location within the fMRI sensorimotor activations was
transferred to the high resolution anatomical MRI images by three human fMRI
experts and by three automatic coregistration programs. The 3D distance between
the median localizations of experts and programs was calculated and compared
between patients and healthy subjects. Results show that fMRI localization on
anatomical images was better with the experts than software in 70% of the cases
and that software performance was worse for patients than healthy subjects
(unpaired t-test: P = 0.040). With 45.6 mm the maximum disagreement between
experts and software was quite large. The inter-rater consistency was better for
the fMRI experts compared to the coregistration programs (ANOVA: P = 0.003). We
conclude that results of automatic coregistration should be evaluated carefully,
especially in case of clinical application.
PMID- 17036155
TI - Intradiscal corticosteroid injections in spondylotic cervical radiculopathy.
AB - The purpose of this study was to evaluate treatment outcomes with intradiscal
injection of corticosteroids (IDIC) in cervical spondylotic radiculopathy. Twenty
consecutive patients were treated with intradiscal injection of 25 mg of acetate
of prednisolone under fluoroscopic control. All patients had previously received
a nonsurgical treatment for at least 3 months without success. Outcomes were
assessed 1, 3 and 6 months after IDIC. Radicular pain reduction as scored on a
visual analogue scale (VAS 100-mm length) was statistically significant at 1
month (19.0+/-28.0 mm; p=0.008), 3 months (25.2+/-27.5 mm; p=0.002), and 6 months
(24.6+/-28.4 mm; p=0.001). In all, 40% of treated patients described at least 50%
pain improvement 6 months after treatment. Four patients had complete relief of
radicular pain. In conclusion, IDIC should be an alternative in the nonsurgical
management of cervical spondylotic radiculopathy.
PMID- 17036156
TI - Assessment of colonic transit time using MRI: a feasibility study.
AB - The aim of this pilot study was to evaluate a new, non-invasive examination
method using MRI for the quantification of the colonic transit time after oral
administration of gadolinium-saline solution filled capsules. Healthy volunteers
without previous or acute symptoms of gastrointestinal disorders were enrolled.
After a 3-day diet for the standardization of gastrocolonic content the
volunteers swallowed five Gd-DTPA/saline 0.9%-filled capsules. Seven different
concentrations of Gd-DTPA/saline 0.9% solution between 1:0 and 0:1 were tested in
a dilution series. Following ingestion of capsules, coronal Flash T1 and True
Fisp sequences using a 1.5 Tesla system were obtained at 0 h, 3 h, 6 h, 12 h, 24
h, 36 h and 60 h. Sequences were analyzed by two independent experts for locating
the capsules. Overall colonic transit time was separately analyzed for both
genders. Fifteen healthy volunteers (7 females, 8 males; mean age 34+/-13 years)
were enrolled. The phantom study provided the best contrast in both the T1-and T2
weighted sequences defining a ratio of 1:10 for Gd-DTPA/saline 0.9% solution. The
mean transit time accounted for 41+/-9 h in women and for 31+/-10 h in men. MRI
is an adequate method for the assessment of colonic transit time offering the
advantages of no exposure to radiation, short examination time, possible dynamic
evaluation of the transit and the practicability in terms of a future adoption to
clinical routine.
PMID- 17036157
TI - mini-PAT (Peer Assessment Tool): a valid component of a national assessment
programme in the UK?
AB - PURPOSE: To design, implement and evaluate a multisource feedback instrument to
assess Foundation trainees across the UK. METHODS: mini-PAT (Peer Assessment
Tool) was modified from SPRAT (Sheffield Peer Review Assessment Tool), an
established multisource feedback (360 degrees ) instrument to assess more senior
doctors, as part of a blueprinting exercise of instruments suitable for
assessment in Foundation programmes (first 2 years postgraduation). mini-PAT's
content validity was assured by a mapping exercise against the Foundation
Curriculum. Trainees' clinical performance was then assessed using 16 questions
rated against a six-point scale on two occasions in the pilot period. Responses
were analysed to determine internal structure, potential sources of bias and
measurement characteristics. RESULTS: Six hundred and ninety-three mini-PAT
assessments were undertaken for 553 trainees across 12 Deaneries in England,
Wales and Northern Ireland. Two hundred and nineteen trainees were F1s or PRHOs
and 334 were F2s. Trainees identified 5544 assessors of whom 67% responded. The
mean score for F2 trainees was 4.61 (SD = 0.43) and for F1s was 4.44 (SD = 0.56).
An independent t test showed that the mean scores of these 2 groups were
significantly different (t = -4.59, df 390, p < 0.001). 43 F1s (19.6%) and 19 F2s
(5.6%) were assessed as being below expectations for F2 completion. The factor
analysis produced 2 main factors, one concerned clinical performance, the other
humanistic qualities. Seventy-four percent of F2 trainees could have been
assessed by as few as 8 assessors (95% CI +/-0.6) as they either scored an
overall mean of 4.4 or above or 3.6 and below. Fifty-three percent of F1 trainees
could have been assessed by as few as 8 assessors (95% CI +/-0.5) as they scored
an overall mean of 4.5 or above or 3.5 and below. The hierarchical regression
when controlling for the grade of trainee showed that bias related to the length
of the working relationship, occupation of the assessor and the working
environment explained 7% of the variation in mean scores when controlling for the
year of the Foundation Programme (R squared change = 0.06, F change = 8.5,
significant F change <0.001). CONCLUSIONS: As part of an assessment programme,
mini-PAT appears to provide a valid way of collating colleague opinions to help
reliably assess Foundation trainees.
PMID- 17036158
TI - Impairment of flow mediated vasodilatation of brachial artery in patients with
primary hyperparathyroidism.
AB - BACKGROUND: Hyperparathyroid condition might influence endothelial cells. The aim
of this study was to assess flow mediated dilatation (FMD) in patients with
primary hyperparathyroidism (PHPT). METHODS: We prospectively evaluated 21
patients with PHPT (9 women, 12 men; aged 50 +/- 11 years, serum calcium 11.6 +/-
0.7 mg/dl, intact parathyroid hormone (iPTH) 489 +/- 495 pg/ml) and 27 healthy
control subjects (13 women, 14 men; aged 49 +/- 10 years, serum calcium 9.4 +/-
0.5 mg/dl, iPTH 28 +/- 8.5 pg/ml). Endothelial function, measured as FMD of the
brachial artery using ultrasound, was calculated in two groups. To avoid
confounding factors, conditions known to affect endothelial function like
diabetes mellitus, hypertension, dyslipidemia, smoking, coronary and peripheral
artery disease were excluded from both groups. RESULTS: FMD was lower in patients
with PHPT than that in those without (10.2 +/- 5.8 vs. 19.8 +/- 5.8, P = 0.0001).
FMD negatively correlated with serum calcium (r = -0.55, P = 0.002). CONCLUSION:
Endothelium-dependent FMD may impair in patients with PHPT compared to controls.
Endothelial dysfunction can contribute to the deleterious cardiovascular effects
of PTH excess. Therapy to reduce or retard endothelial dysfunction in patients
with PHPT may lead to decreased cardiovascular morbidity and mortality.
PMID- 17036159
TI - 13C-detected HN(CA)C and HMCMC experiments using a single methyl-reprotonated
sample for unambiguous methyl resonance assignment.
AB - Methyl groups provide an important source of structural and dynamic information
in NMR studies of proteins and their complexes. For this purpose sequence
specific assignments of methyl 1H and 13C resonances are required. In this paper
we propose the use of 13C-detected 3D HN(CA)C and HMCMC experiments for
assignment of methyl 1H and 13C resonances using a single selectively methyl
protonated, perdeuterated and 13C/15N-labeled sample. The high resolution
afforded in the 13C directly-detected dimension allows one to rapidly and
unambiguously establish correlations between backbone HN strips from the 3D
HN(CA)C spectrum and methyl group HmCm strips from the HMCMC spectrum by aligning
all possible side-chain carbon chemical shifts and their multiplet splitting
patterns. The applicability of these experiments for the assignment of methyl 1H
and 13C resonances is demonstrated using the 18.6 kDa B domain of the Escherichia
coli mannose transporter (IIBMannose).
PMID- 17036160
TI - Sensitivity improvement for correlations involving arginine side-chain
Nepsilon/Hepsilon resonances in multi-dimensional NMR experiments using broadband
15N 180 degrees pulses.
AB - Due to practical limitations in available 15N rf field strength, imperfections in
15N 180 degrees pulses arising from off-resonance effects can result in
significant sensitivity loss, even if the chemical shift offset is relatively
small. Indeed, in multi-dimensional NMR experiments optimized for protein
backbone amide groups, cross-peaks arising from the Arg guanidino 15Nepsilon
(approximately 85 ppm) are highly attenuated by the presence of multiple INEPT
transfer steps. To improve the sensitivity for correlations involving Arg
Nepsilon-Hepsilon groups, we have incorporated 15N broadband 180 degrees pulses
into 3D 15N-separated NOE-HSQC and HNCACB experiments. Two 15N-WURST pulses
incorporated at the INEPT transfer steps of the 3D 15N-separated NOE-HSQC pulse
sequence resulted in a approximately 1.5-fold increase in sensitivity for the Arg
Nepsilon-Hepsilon signals at 800 MHz. For the 3D HNCACB experiment, five 15N
Abramovich-Vega pulses were incorporated for broadband inversion and refocusing,
and the sensitivity of Arg1Hepsilon-15Nepsilon-13Cgamma/13Cdelta correlation
peaks was enhanced by a factor of approximately 1.7 at 500 MHz. These experiments
eliminate the necessity for additional experiments to assign Arg 1Hepsilon and
15Nepsilon resonances. In addition, the increased sensitivity afforded for the
detection of NOE cross-peaks involving correlations with the 15Nepsilon/1Hepsilon
of Arg in 3D 15N-separated NOE experiments should prove to be very useful for
structural analysis of interactions involving Arg side-chains.
PMID- 17036161
TI - Backbone assignment of the 98 kDa homotrimeric yeast PCNA ring.
PMID- 17036162
TI - NMR assignment of 1H, 13C and 15N resonances of the truncated Escherichia coli
RcsC (700-949), including the phosphoreceiver domain.
PMID- 17036163
TI - High expression of APOBEC3G in patients infected with hepatitis C virus.
AB - APOBEC3G (an apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G;
also known as CEM15), a member of the APOBEC family, which possesses cytidine
deaminase activity that causes C/G to T/A transition mutations in virus genomes
such as human immunodeficiency virus 1 and hepatitis B virus, is reported to play
an important role in host-defense mechanisms. However, APOBEC3G expression in
patients infected with chronic hepatitis C virus (HCV), of which there are
currently more than 170 million worldwide, has not yet been well studied. We
investigated this issue herein, and demonstrated an increased expression of
APOBEC3G in both hepatocytes and lymphocytes of chronic hepatitis patients
infected with HCV. Transfection of the NS5A gene, but not any other non
structural protein genes of HCV tested, to the hepatocellular carcinoma cell line
enhanced APOBEC3G expression. Incubation of the cells with interferon also
resulted in the augmentation. These results may provide new insight into the
pathogenesis of chronic HCV infection.
PMID- 17036164
TI - Brain-type creatine kinase BB-CK interacts with the Golgi Matrix Protein GM130 in
early prophase.
AB - Creatine kinase (CK) isoenzymes are essential for storing, buffering and
intracellular transport of "energy-rich" phosphate compounds in tissues with
fluctuating high energy demand such as muscle, brain and other tissues and cells
where CK is expressed. In brain and many non-muscle cells, ubiquitous cytosolic
"brain-type" BB-CK and ubiquitous mitochondrial CK (uMtCK) act as components of a
phosphocreatine shuttle to maintain cellular energy pools and distribute energy
flux. To date, still relatively little is known about direct coupling of
functional dimeric BB-CK with other partner proteins or enzymes that are
important for cell function. Using a global yeast two-hybrid (Y2H) screen with
monomeric B-CK as bait and a representative brain cDNA library to search for
interaction partners of B-CK with proteins of the brain, we repeatedly identified
the cis-Golgi Matrix protein (GM130) as recurrent interacting partner of B-CK.
Since HeLa cells also express both BB-CK and GM130, we subsequently used this
cellular model system to verify and characterize the BB-CK-GM130 complex by GST
pulldown experiments, as well as by in vivo co-localization studies with confocal
microscopy. Using dividing HeLa cells, we report here for the first time that
GM130 and BB-CK co-localize specifically in a transient fashion during early
prophase of mitosis, when GM130 plays an important role in Golgi fragmentation
that starts also at early prophase. These data may shed new light on BB-CK
function for energy provision for Golgi-fragmentation that is initiated by cell
signalling cascades in the early phases of mitosis.
PMID- 17036166
TI - Pelvic prolapse and urinary incontinence in nulliparous college women in relation
to paratrooper training.
AB - The objective of this study was to determine whether paratrooper training is
associated with pelvic support defects or urinary incontinence. Nulliparous women
at The United States Military Academy were examined using the Pelvic Organ
Prolapse Quantification System and completed a questionnaire regarding
incontinence and exercise prior to undergoing summer military training. The exam
and questionnaire were repeated following training. One hundred sixteen women
completed the study (80.6%), 37 of whom had attended paratrooper training. Women
who attended paratrooper training were significantly more likely to have stage II
prolapse (RR=2.72, 1.37 50 years
who have completed at least five marathon races during the preceding 3 years and
do not suffer from coronary artery disease, angina nor diabetes mellitus are
studied to assess the predictive value of established and modern imaging- based
and biochemical cardiovascular risk factors. Laboratory parameters including
clinical chemistry, hematology and hormone measurements are determined. Lifestyle
related risk factors, psychosocial and socioeconomic variables are explored using
standardized questionnaires. Coronary, carotid, femoral and aortic
atherosclerosis is measured using electronbeam computed tomography and
ultrasound. In addition, a resting ECG, a bicycle stress test and heart rate
variability are performed. Myocardial morphology and function are assessed using
echocardiography and magnetic resonance imaging. Participants are invited to
compete in a marathon race to quantify the association of coronary
atherosclerosis with marathon-related changes of cardiac troponin levels and the
extent of marathon-induced inflammation. At the cellular level, the effect on the
amount of circulating progenitor cells (EPCs) is determined by FACS analysis.
Changes in laboratory parameters and hormone levels are also studied. Annual long
term follow-up including hospital records and death certificates is performed.
Data are compared with those from a general unselected cohort from the Heinz
Nixdorf Recall Study. CONCLUSION: This study should contribute to cardiovascular
risk assessment in the growing number of masters marathon runners with a focus on
assessing the predictive value of modern imaging techniques and biochemical
markers for comprehensive risk stratification.
PMID- 17036190
TI - [Ironman and cardiac transplantation. High sporting exercise capacity before and
after cardiac transplantation].
AB - The case of a 45-year-old man is reported who was an active competitive sportsman
up to his 38th year. In fall of 1998, exercise limitation was noted. The
cardiologic work-up revealed dilated cardiomyopathy. In spite of intensive
medical therapy clinical course deteriorated within the next 3 years, cardiologic
findings and a follow-up in CPET (cardiopulmonary exercise testing) showed a
rapid decline. In May 2002, he was listed for cardiac transplantation. In August
2003, an orthotopic bicaval cardiac transplantation was performed at the
University of Gottingen, Germany. The patient was followed regularly in the
office. Physical exercise capacity increased significantly and he was able to
participate in the 10-km New Year's run of 2003. Since 2004, he has been working
very successfully as a coach for competitive swimmers. Based on CPET findings,
actual views and concepts regarding the pathophysiology and training of chronic
heart failure are discussed and the question is raised whether and in which
respect a sportive predisposition favors the clinical outcome.
PMID- 17036191
TI - Pneumopericardium followed by pericardial effusion after thoracic trauma and
pacemaker implantation.
PMID- 17036192
TI - [Postconditioning: a brief review].
AB - Preconditioning is the most effective form of cardioprotection that can be
induced via different interventions before a longer-lasting ischemia (= index
ischemia). Preconditioning can be induced by short bouts of ischemia, several
pharmaceuticals (e.g., adenosine), and volatile anesthetics. A brief ischemia of
an organ other than the heart can likewise initiate protection of the heart,
which has been called preconditioning at a distance or remote preconditioning.
According to the more recent literature, short bouts of ischemia after an index
ischemia can also initiate cardioprotection, e.g., improve postischemic
dysfunction or reduce infarct size, which has been called postconditioning. Such
a postconditioning can also be elicited at a distant organ, termed remote
postconditioning. It is the aim of this short review to characterize
preconditioning and in particular postconditioning, describe possible mechanisms,
and call attention to the clinical relevance.
PMID- 17036193
TI - Guest editorial. Special issue on neuroendocrine tumors.
PMID- 17036194
TI - Functional imaging of neuroendocrine tumours with PET.
AB - Several pathophysiological attributes of neuroendocrine tumours (NET) can be
addressed by specific radiolabelled probes. This paper provides an overview on
the different radiopharmaceuticals that have been developed for Positron Emission
Tomography (PET) of neuroendocrine tumours. A review of the literature on 18F
fluordeoxyglucose (FDG), biogenic amine precursors, somatostatin analogues and
hormone syntheses markers is presented. Due to the highly specific tracers that
lack any clear anatomical landmarking the advantages of integrated PET/CT are
obvious. Amine precursors should be employed in most gastroenteropancreatic NET,
FDG should be preserved for more aggressive, less differentiated NETs.
Somatostatin analogues are the most promising tracers, since they can improve
dosimetry in cases in which radiopeptide therapies are planned. In conclusion,
the individual diagnostic approach using PET or the integrated PET/CT should be
tailored depending on the histological classification and the differentiation of
the tumour.
PMID- 17036195
TI - Neuroendocrine tumors secreting growth hormone-releasing hormone:
Pathophysiological and clinical aspects.
AB - Hypothalamic GHRH is secreted into the portal system, binds to specific surface
receptors of the somatotroph cell and elicits intracellular signals that modulate
pituitary GH synthesis and/or secretion. Moreover, GHRH is synthesized and
expressed in multiple extrapituitary tissues. Excessive peripheral production of
GHRH by a tumor source would therefore be expected to cause somatotroph cell
hyperstimulation, increased GH secretion and eventually pituitary acromegaly.
Immunoreactive GHRH is present in several tumors, including carcinoid tumors,
pancreatic cell tumors, small cell lung cancers, endometrial tumors, adrenal
adenomas, and pheochromocytomas which have been reported to secrete GHRH.
Acromegaly in these patients, however, is uncommon. The distinction of pituitary
vs. extrapituitary acromegaly is extremely important in planning effective
management. Regardless of the cause, GH and IGF-1 are invariably elevated and GH
levels fail to suppress (<1 microg/l) after an oral glucose load in all forms of
acromegaly. Dynamic pituitary tests are not helpful in distinguishing acromegalic
patients with pituitary tumors from those harbouring extrapituitary tumors.
Plasma GHRH levels are usually elevated in patients with peripheral GHRH
secreting tumors, and are normal or low in patients with pituitary acromegaly.
Unique and unexpected clinical features in an acromegalic patient, including
respiratory wheezing or dyspnea, facial flushing, peptic ulcers, or renal stones
sometimes are helpful in alerting the physician to diagnosing non pituitary
endocrine tumors. If no facility to measure plasma GHRH is available, and in the
absence of MRI evidence of pituitary adenoma, a CT scan of the thorax and
abdominal ultrasound could be performed to exclude with good approximation the
possibility of an ectopic GHRH syndrome. Surgical resection of the tumor
secreting ectopic GHRH should be the logical approach to a patient with ectopic
GHRH syndrome. Standard chemotherapy directed at GHRH-producing carcinoid tumors
is generally unsuccessful in controlling the activated GH axis. Somatostatin
analogs provide an effective option for medical management of carcinoid patients,
especially those with recurrent disease. In fact, long-acting somatostatin
analogs may be able to control not only the ectopic hormonal secretion syndrome,
but also, in some instances, tumor growth. Therefore, although cytotoxic
chemotherapy, pituitary surgery, or irradiation still remain available
therapeutic options, long-acting somatostatin analogs are now preferred as a
second-line therapy in patients with carcinoid tumors and ectopic GHRH-syndrome.
PMID- 17036196
TI - PRKAR1A mutations in primary pigmented nodular adrenocortical disease.
AB - Primary Pigmented Nodular Adrenocortical Disease (PPNAD) is a rare primary
bilateral adrenal defect causing corticotropin-independent Cushing's syndrome. It
occurs mainly in children and young adults. Macroscopic appearance of the
adrenals is characteristic with small pigmented micronodules observed in the
cortex. PPNAD is most often diagnosed in patients with Carney complex (CNC), but
it can also be observed in patients without other manifestations or familial
history (isolated PPNAD). The CNC is an autosomal dominant multiple neoplasia
syndrome characterized by the association of myxoma, spotty skin pigmentation and
endocrine overactivity. One of the putative CNC genes has been identified as the
gene of the regulatory R1A subunit of protein kinase A (PRKAR1A), located at
17q22-24. Germline heterozygous inactivating mutations of PRKAR1A have been
reported in about 45% of patients with CNC, and up to 80% of CNC patients with
Cushing's syndrome due to PPNAD. Interestingly, such inactivating germline
PRKAR1A mutations have also been found in patients with isolated PPNAD. The hot
spot PRKAR1A mutation termed c.709[-7-2]del6 predisposes mostly to isolated
PPNAD, and is the first clear genotype/phenotype correlation described for this
gene. Somatic inactivating mutations of PRKAR1A have been observed in
macronodules of PPNAD and in sporadic cortisol secreting adrenal adenomas.
Isolated PPNAD is a genetic heterogenous disease, and recently inactivating
mutations of the gene of the phosphodiesterase 11A4 (PDE11A4) located at 2q31
2q35 have been identified in patients without PRKAR1A mutations. Interestingly,
both PRKAR1A and PDE11A gene products control the cAMP signaling pathway, which
can be altered at various levels in endocrine tumors.
PMID- 17036198
TI - Ceramide induces apoptosis via a peroxisome proliferator-activated receptor gamma
dependent pathway.
AB - Both of ceramide and PPARgamma ligand can trigger cancer cell apoptosis. We here
show that C2-ceramide can modulate PPARgamma expression level and its
transcriptional activity and results in apoptosis in HT29 cells. Administration
of PPARgamma specific antagonist GW9662 partially prevents HT29 cells from
apoptosis. Furthermore, MAP kinase pathway provided a potential modulation
mechanism for PPARgamma pathway related with ceramide. Our results are the first
to demonstrate that C2-ceramide induces apoptosis via a PPARgamma-dependent
pathway.
PMID- 17036199
TI - Involvement of both caspase-dependent and -independent pathways in apoptotic
induction by hexaminolevulinate-mediated photodynamic therapy in human lymphoma
cells.
AB - Photodynamic therapy (PDT) is a cancer treatment based on the interaction of a
photosensitizer, light and oxygen. PDT with the endogenous photosensitizer,
protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) or its
derivatives is a modification of this treatment modality with successful
application in dermatology. However, the mechanism of cell destruction by ALA-PDT
has not been elucidated. In this study a human T-cell lymphoma Jurkat cell line
was treated with PDT using hexaminolevulinate (HAL, hexylester of ALA). Four
hours following treatment nearly 80% of the cells exhibited typical apoptotic
features. Mitochondrial pro-apoptotic proteins were evaluated by Western blots in
subcellular fractionated samples. PDT caused cytosolic translocation of
cytochrome c and nuclear redistribution of apoptosis-inducing factor (AIF), but
the release of mitochondrial Smac/DIABLO, Omi/HtrA2 and EndoG was not observed.
The release of cytochrome c was followed by the cleavage of caspase-9 and caspase
3 as well as its downstream substrates, together with oligonucleosomal DNA
fragmentation. The pan-caspases inhibitor, z-VAD.fmk, prevented oligonucleosomal
DNA fragmentation, but failed to inhibit PDT-mediated apoptosis. The apoptotic
induction by AIF-mediated caspase-independent pathway was also found after HAL
PDT with large-scale DNA fragmentation in the presence of z-VAD.fmk. These
results demonstrate that cytochrome c-mediated caspase-dependent pathway and AIF
induced caspase-independent pathway are simultaneously involved in the apoptotic
induction by PDT. When the cytochrome c-induced caspase-dependent pathway is
blocked, the cells go into apoptosis via AIF-mediated pathway, clearly
demonstrating that the cytochrome c-mediated caspase-dependent pathway is not
required for such apoptotic induction. This finding may have an impact on
improved PDT effectiveness.
PMID- 17036197
TI - RET and neuroendocrine tumors.
AB - The RET proto-oncogene encodes a receptor tyrosine kinase that is a main
component of the signaling pathway activated by the glial cell line-derived
neurotrophic factor family ligands. Gene targeting studies revealed that
signaling through RET plays a crucial role in neuronal and renal organogenesis.
It is well-known that germline mutations in RET lead to the human inherited
diseases, multiple endocrine neoplasia type 2 (MEN 2) and Hirschsprung's disease,
and that somatic rearrangements of RET cause papillary thyroid carcinoma. Due to
marked advances in understanding of the molecular mechanisms of the development
of MEN 2, a consensus on MEN 2 management associated with RET status is being
reached and currently put into general use as a guideline. In this review, we
summarize progress in the study of RET from bench to bedside, focusing on
pathophysiology of neuroendocrine tumors.
PMID- 17036200
TI - Yersinia YopP-induced apoptotic cell death in murine dendritic cells is partially
independent from action of caspases and exhibits necrosis-like features.
AB - Yersinia outer protein P (YopP) is a virulence factor of Yersinia enterocolitica
that is injected into the cytosol of host cells where it targets MAP kinase
kinases (MKKs) and inhibitor of kappaB kinase (IKK)-beta resulting in inhibition
of cytokine production as well as induction of apoptosis in murine macrophages
and dendritic cells (DC). Here we show that DC death was only partially prevented
by the broad spectrum caspase inhibitor zVAD-fmk, indicating simultaneous caspase
dependent and caspase-independent mechanisms of cell death induction by YopP.
Microscopic analyses and measurement of cell size demonstrated necrosis-like
morphology of caspase-independent cell death. Application of zVAD-fmk prevented
cleavage of procaspases and Bid, decrease of the inner transmembrane
mitochondrial potential DeltaPsi(m) and mitochondrial release of cytochrome c.
From these data we conclude that YopP-induced activation of the mitochondrial
death pathway is mediated upstream via caspases. In conclusion, our results
suggest that YopP simultaneously induces caspase-dependent apoptotic and caspase
independent necrosis-like death in DC. However, it has to be resolved if necrosis
like DC death occurs independently from apoptotic events or as an apoptotic
epiphenomenon.
PMID- 17036202
TI - What is the optimal time of surgical intervention after an acute attack of
sigmoid diverticulitis: early or late elective laparoscopic resection?
AB - PURPOSE: This prospective study was designed to check the ideal time of surgical
intervention by comparing the results of early elective laparoscopic sigmoid
resection after an inflammatory attack with those of late elective resection
during the inflammation-free interval. METHODS: A total of 210 patients (114
males) underwent laparoscopic resection for acute sigmoid diverticulitis between
1999 and 2005. They were prospectively divided into two groups: Group I with an
early elective sigmoid resection (5-8 days after initial antibiotic treatment);
Group II in the inflammation-free interval (4-6 weeks after initial
hospitalization). RESULTS: There was no difference between the groups with regard
to age (55.7 years), American Society of Anesthesiologists score (1.86), previous
diseases, and extent of inflammation. After surgery, 156 patients (74.3 percent)
were complication-free. There was a total of ten conversions (Group I, 9; Group
II, 1; P<0.05). Minor complications developed in 42 patients (abdominal wall
abscess=24, intestinal atony=6, hematoma=9, urinary tract infection=2). Eight
patients in Group I (P<0.05) developed anastomotic leaks. None of the patients
died. CONCLUSIONS: In the majority of patients, laparoscopic sigmoid resection in
sigmoid diverticulitis can be performed without conversion. Patients who
underwent surgery in the inflammation-free interval had a lower complication rate
than those submitted to early elective resection. In our patient population, we
were able to show that surgery in the inflammation-free interval significantly
reduces postoperative morbidity. It is thus preferable for patients with sigmoid
diverticulitis to receive initial antibiotic treatment and then undergo late
elective laparoscopic sigmoid resection.
PMID- 17036203
TI - The impact of surgery for colorectal cancer on quality of life and functional
status in the elderly.
AB - PURPOSE: Colorectal cancer is a common diagnosis in the elderly. Frequently
concerns arise about outcomes after surgery, and little is known about
postoperative quality of life in this older group after major bowel surgery. The
objective of this study was to compare quality of life and functional status of
elderly patients (older than aged 80 years) who have undergone surgery for
colorectal cancer with a younger (younger than aged 70 years), procedure-matched
control group. METHODS: Patients in the case (older than aged 80 years) and
control groups (younger than aged 70 years) were identified from the colorectal
cancer database at Mount Sinai Hospital, Toronto, Canada. All had treatment for
colorectal cancer within the last five years. Patients were surveyed by mail
using the European Organization for Research and Treatment of Cancer quality of
life scales specific to cancer and colorectal cancer (EORTC-C30 and EORTC-CR38)
and the Short Form-36. Student's t-test was used to test differences. RESULTS:
There were 29 patients in each of the groups. The current average ages were 83.2
(standard deviation=2.79) years, and 67.7 (standard deviation=5.1) years,
respectively. The two groups scored similarly on the European Organization for
Research and Treatment of Cancer quality of life scales in all domains except
physical functioning, functional role, micturition, and stoma-related problems.
Similarly, the mean scores of the Short Form-36 were similar with the exception
of the vitality domain. Most patients did not require special assistance or
alternate living arrangements after discharge from the hospital, and most
patients seemed to be able to return to their preoperative level of functioning.
However, stoma care was a greater concern to the elderly. CONCLUSIONS: Elderly
patients older than aged 80 years who are selected for surgery have a quality of
life comparable to younger patients in most respects. Therefore, colorectal
cancer surgery may be offered to the highly functioning elderly with the
expectation of a good quality of life postoperatively.
PMID- 17036204
TI - Fecal impaction in adults: report of 30 cases of seed bezoars in the rectum.
AB - PURPOSE: Seed bezoars in the rectum have been considered an uncommon cause of
fecal impaction in adults. Although there have been several reports on sunflower
seed bezoars, seed bezoars from the fruit of the prickly pear cactus and
watermelon have received little notice. This study was designed to determine the
frequency of fecal impaction by seed bezoars in the rectum and their clinical
characteristics in adults. METHODS: A retrospective review of the medical records
of patients hospitalized with the diagnosis of fecal impaction during a ten-year
period. RESULTS: During the study period (January 1996 to December 2005), 55
patients were hospitalized at the Western Galilee Hospital, in northern Israel,
with the diagnosis of fecal impaction. Phytobezoars were found in 30 patients (55
percent). The seed bezoars were composed of prickly pear seeds in 12 patients,
watermelon seeds in 10 patients, sunflower seeds in 4 patients, popcorn kernels
in 1 patient, and pomegranate seeds in 1 patient. The Jew:Arab ratio for seed
bezoars was 7:23. Seventy-three patients had seedless fecal masses with a
Jew:Arab ratio of 58:15. All 30 patients with bezoar underwent digital
disimpaction under general anesthesia. Only 21 of 73 patients with seedless fecal
masses were treated under general anesthesia. CONCLUSIONS: Seed bezoars found in
the rectum were the most common cause of fecal impaction requiring
hospitalization, probably to the result of the eating habits in the Middle East.
The consumption of seeds with shell fragments or fruits containing many seeds
(such as the prickly pear) should be accompanied by the awareness that large
quantities may cause fecal impaction.
PMID- 17036205
TI - Lower limb acute compartment syndrome after colorectal surgery in prolonged
lithotomy position.
AB - PURPOSE: Acute compartment syndrome in patients undergoing prolonged colorectal
procedures is uncommon but can have catastrophic consequences for the patient
with the development of metabolic acidosis, myoglobinuric renal failure,
Volkmann's contracture, limb loss, and death. The potential to produce long-term
disability in a patient has important medicolegal implications, particularly if
the complication is avoidable. Why only some patients develop acute compartment
syndrome is not fully understood. The purpose of this study was to highlight
current knowledge and suggested prevention strategies. METHODS: A review of the
relevant English language articles was performed on the basis of a MEDLINE search
of the keywords: acute compartment syndrome, lithotomy position, reperfusion
injury, and fasciotomy. RESULTS: Different factors play a role: lithotomy
position with or without head down, ankle and knee position, external compression
for deep vein thrombosis prophylaxis, method of leg support, duration of surgery,
and physiologic factors, such as gender, age, and body mass index. All efforts
should be directed to prevent the establishment of acute compartment syndrome and
there are accepted suggestions, such as limiting the time of leg elevation,
positioning the leg below the atrium level, and monitoring postoperatively
patients at risk. There is still debate on the intraoperative use of pulse
oximetry to detect hypoperfusion and the appropriate use of sequential
compression devices and antithromboembolic stockings. CONCLUSIONS: Acute
compartment syndrome is uncommon but cases have been reported after prolonged
pelvic procedures in the lithotomy position and it is a preventable condition.
More research is required to set clear guidelines on patient positioning during
surgery.
PMID- 17036206
TI - The importance of local subcutaneous fat thickness in pilonidal disease.
AB - PURPOSE: This study was designed to investigate the local subcutaneous fat
thickness in sacrococcygeal pilonidal disease. METHODS: Subcutaneous fat
thickness was measured by ultrasonography in 125 patients with sacrococcygeal
pilonidal disease and 125 age-matched, body mass index-matched and gender-matched
controls. RESULTS: The sacrococcygeal subcutaneous fat thickness was 14.4 +/- 2.9
mm, 18.3 +/- 3.1 mm, and 22 +/- 2.2 mm, respectively, in normal, overweight, and
obese patients with sacrococcygeal pilonidal disease and 9.1 +/- 3.1 mm, 11.3 +/-
2.6 mm, and 20 +/- 1.8 mm, respectively, in normal, overweight, and obese
controls. Sacrococcygeal fat was significantly thicker in normal and overweight
patients with pilonidal disease compared with controls with same body mass index
(P< 0.01). There were no significant differences in fat thickness between obese
patients and obese controls (P > 0.05). CONCLUSIONS: Sacrococcygeal fat
thickness, as a local factor, is closely associated with pilonidal disease.
PMID- 17036208
TI - Preoperative tegafur suppositories for resectable rectal cancer: phase II trial.
AB - PURPOSE: Preoperative radiochemotherapy for rectal cancer causes a high rate of
moderate-to-severe toxicities and is associated with only moderate survival
benefits. A simpler, safer, and more convenient treatment would be preferable.
Preoperative tegafur suppositories (1,500 mg/day) for at least 14 days were
piloted. METHODS: A total of 129 patients with resectable rectal cancer were
enrolled. The primary end points were pathologic response, adverse events, rate
of sphincter-sparing surgery, recurrence, and survival. RESULTS: The total dose
of tegafur ranged from 21 to 78 (mean, 32) g. The anal sphincter was preserved in
60.5 percent with microscopic no residual tumor (R0). The overall morbidity rate
was 32 percent. Wound infection occurred in 13.2 percent of cases and anastomotic
leakage in 9 percent of cases. Pathologic responses were observed in 70 percent
of patients, with a complete necrosis occurring in 3.9 percent, two-thirds or
more necrosis in 6.2 percent, one-third or more but less than two-thirds necrosis
in 18.6 percent, and less than one-third necrosis in 41.9 percent. The mean total
dose that patients showing complete or two-thirds or more necrosis received was
42.8 +/- 6.4 g (P = 0.01) compared with 31.6 +/- 1.2 g administered to patients
showing less than two-thirds necrosis. Adverse events were observed in 15.6
percent of patients overall, and Grade III or IV events were observed in 2.3
percent of patients. During a median follow-up of 48 months, distant metastasis
occurred in 14.7 percent of patients and local recurrence occurred in 6.2 percent
of patients. The four-year, disease-free and overall survival rates were 67.6 and
80.1 percent, respectively. CONCLUSIONS: Preoperative tegafur suppositories are
associated with low toxicity and may lead to anal sphincter-sparing surgery with
acceptable postoperative complications and favorable local and distal control.
PMID- 17036209
TI - Toward a Wolbachia multilocus sequence typing system: discrimination of Wolbachia
strains present in Drosophila species.
AB - Among the diverse maternally inherited symbionts in arthropods, Wolbachia are the
most common and infect over 20% of all species. In a departure from traditional
genotyping or phylogenetic methods relying on single Wolbachia genes, the present
study represents an initial Multilocus Sequence Typing (MLST) analysis to
discriminate closely related Wolbachia pipientis strains, and additional data on
sequence diversity in Wolbachia. We report a new phylogenetic characterization of
four genes (aspC, atpD, sucB, and pdhB), and provide an expanded analysis of
markers described in previous studies (16S rDNA, ftsZ, groEL, dnaA, and gltA).
MLST analysis of the bacterial strains present in 16 different Drosophila
Wolbachia associations detected four distinct clonal complexes that also
corresponded to maximum-likelihood identified phylogenetic clades. Among the 16
associations analyzed, six could not be assigned to MLST clonal complexes and
were also shown to be in conflict with relationships predicted by maximum
likelihood phylogenetic inferences. The results demonstrate the discriminatory
power of MLST for identifying strains and clonal lineages of Wolbachia and
provide a robust foundation for studying the ecology and evolution of this
widespread endosymbiont.
PMID- 17036210
TI - Phage displayed Bacillus thuringiensis Cry1Ba4 toxin is toxic to Plutella
xylostella.
AB - We constructed recombinant phage particles displaying the Bacillus thuringiensis
Cry1Ba4 active toxin using the pfUSE5 and pComb3X phagemid vectors. The
recombinant phage particles were screened and evaluated for displayed
biologically active Cry1Ba4 toxin against the target insect larvae. Concurrent
expression of Cry1Ba4 protoxin was carried out using the pETBlue -2 plasmid
expression vector in Escherichia coli Tuner (DE3)pLacI and the protoxin was
successfully expressed at a size of 129 kDa. In the bioassay, 3.30 mg crude
extract of Cry1Ba4 protoxin, 9.35 x 10(9) TU and 7.70 x 10(9) TU of induced
recombinant phage particles carrying Cry1Ba4 active toxin displayed on pComb3X
and pFUSE5, respectively, demonstrated mortality of greater than 85% against
Plutella xylostella (third-instar) within 48 hours. Thus, we have successfully
displayed the Cry1Ba4 activated toxin on the surface of a phage and demonstrated
toxicity towards larvae.
PMID- 17036213
TI - A new approach to flow-batch titration. A monosegmented flow titrator with
coulometric reagent generation and potentiometric or biamperometric detection.
AB - Monosegmented flow analysis (MSFA) has been used as a flow-batch system to
produce a simple, robust, and mechanized titrator that enables true titrations to
be performed without the use of standards. This paper also introduces the use of
coulometry with monosegmented titration by proposing a versatile flow cell.
Coulometric generation of the titrand is attractive for titrations performed in
monosegmented systems, because the reagent can be added without increasing the
volume of sample injected. Also, biamperomeric and potentiometric detection of
titration end-points can increase the versatility of the monosegmented titrator.
The cell integrates coulometric generation of the titrand with detection of end
point by potentiometry or biamperometry. The resulting titrator is a flow-batch
system in which the liquid monosegment, constrained by the interfaces of the
gaseous carrier stream, plays the role of a sample of known volume to be
titrated. The system has been used for determination of ascorbic acid, by
coulometric generation of I2 with biamperometric detection, and for determination
of Fe(II), by coulometric generation of Ce(IV) with potentiometric detection of
the end-point, both in feed supplements.
PMID- 17036211
TI - The effect of calcium and magnesium on the activity of bovicin HC5 and nisin.
AB - Some Gram-positive bacteria produce small peptides (bacteriocins) that have
antimicrobial activity, but many bacteria can become bacteriocin resistant.
Bovicin HC5, a lantibiotic produced by Streptococcus bovis HC5, has the ability
to inhibit nisin-resistant bacteria. Because nisin resistance has in many cases
been correlated with an alteration of lipoteichoic acids or the polar head groups
of membrane phospholipids, we decided to examine the effect of divalent cations
on nisin and bovicin HC5 activity. Both bacteriocins catalyzed potassium efflux
from S. bovis JB1, a non-bacteriocin-producing strain. The addition of large
amounts (100 mM) of calcium or magnesium increased the ability of S. bovis JB1 to
bind Congo red (an anionic dye) and counteracted bacteriocin-mediated potassium
loss. Calcium was more effective than magnesium in decreasing nisin activity, but
the reverse was observed with bovicin HC5. Nisin-resistant S. bovis JB1 cells
bound three times as much Congo red as nisin-sensitive cells, and this result is
consistent with the idea that changes in cell surface charge can be a mechanism
of bacteriocin resistance. The nisin-resistant cells were less susceptible to
bovicin HC5, but bovicin HC5 still caused a 50% depletion of intracellular
potassium. These results indicate that nisin and bovicin HC5 react differently
with the cell surfaces of Gram-positive bacteria.
PMID- 17036214
TI - Quantitative analysis of enzymatic assays using indoxyl-based substrates.
AB - Hydrolysis of indoxyl-based substrates by hydrolytic enzymes is a commonly used
semiquantitative detection system that generates a water-insoluble indigo dye
which is difficult to quantify. This work describes the quantitative analysis and
enzyme kinetics for alkaline phosphatase (AP) and 5-bromo-4-chloro-3-indoxyl
phosphate (BCIP) in solution obtained by applying known solubilization
methodology from the textiles industry to the enzymatic product. This proposal is
based on the reduction of the tetrahalo-indigo blue dye in a basic medium with
the aim of generating its aqueous-soluble parent compound termed indigo white,
which gives a rich yellow color in solution and is fluorescent. A quantitative
ELISA (where a soluble end product is required) is accomplished for first time
using BCIP as substrate.
PMID- 17036215
TI - Detection of preclinical scrapie from serum by infrared spectroscopy and
chemometrics.
AB - In this study we describe a methodology for diagnosing preclinical scrapie
infection in hamsters from serum by a combination of Fourier-transform infrared
(FT-IR) spectroscopy and chemometrics. Syrian hamsters (Mesocricetus auratus)
were orally inoculated with the 263K scrapie agent, or mock-infected, and sera
were obtained at 70, 100 and 130 days post infection (dpi) and at the terminal
stage of scrapie (160 +/- 10 dpi). The analysis of hamster sera by FT-IR
spectroscopy and artificial neural networks (ANN) confirmed results from earlier
studies which had indicated the existence of disease-related structural and
compositional alterations in the sera of infected donors in the terminal stage of
scrapie [Schmitt et al. (2002) Anal Chem 74:3865-3868]. Experimental data from
sera of animals in the preclinical stages of scrapie revealed subtle but
reproducible spectral variations that permitted the identification of a
preclinical scrapie infection at 100 dpi and later, but not at 70 dpi. The IR
spectral features that were discriminatory for the preclinical stages differed
from those of the terminally ill individuals. In order to reliably identify
scrapie-negative as well as preclinical (100 and 130 dpi) and terminal scrapie
positive animals, a hierarchical classification system of independent artificial
neural networks (ANN) was established. A "toplevel" ANN was designed which
discriminates between animals in the terminal stage of scrapie and preclinical
scrapie-positive or control animals. Spectra identified by the "toplevel" ANN as
preclinical or controls were then further analyzed by a second classifier, the
"sublevel" ANN. Using independent external validation procedures, the toplevel
classifier produced an overall classification accuracy of 98%, while the sublevel
classifier yielded an accuracy of 93%, indicating that scrapie-specific serum
markers were also present for preclinical disease stages. Possible spectral
markers responsible for the discrimination capacity of the two different ANNs are
discussed.
PMID- 17036217
TI - Changes in muscle strength and EMG median frequency after anterior cruciate
ligament reconstruction.
AB - The purpose of this study was to monitor neuromuscular changes in quadriceps
femoris muscle at 1 and 3 months after anterior cruciate ligament reconstruction
(ACLR). Changes in isometric muscle strength (MVC), voluntary activation and
surface electromyogram (EMG) parameters were examined in relation to knee
stability, pain and swelling in 31 patients (25 M, 6 F) mean (SD) 30(8) years.
Physically inactive (RC) and sports participants (SC) acted as controls. Median
frequency (Hz) and amplitude (mV) of rectus femoris using Fast Fourier Transform
(FFT) 2(11) was calculated during 5-s isometric contractions at 100, 75, 50 and
25% of MVC. One month after surgery, a significant correlation (P < 0.01) was
found between activation (%) and MVC of injured knee extensors. By 3 months, most
patients were pain free and had achieved full activation but still had muscle
weakness. At 1 and 3 months post-surgery and for all levels of MVC contraction,
the median frequencies of the injured limbs were significantly lower (P < 0.05)
compared to the SC group as were those of the RC group. There was a significant
lowering of the median frequencies of the uninjured limbs compared to the SC
group at 75 and 100% of MVC. The EMG amplitude of the uninjured and injured limbs
mirrored those of the SC and RC groups, respectively. These results support the
view that muscle activation patterns were altered following ACL injury and
surgical repair and may contribute to subsequent changes in muscle fibre
properties during detraining and subsequent retraining.
PMID- 17036218
TI - A new cytoplasmic male sterility system for hybrid seed production in Indian
oilseed mustard Brassica juncea.
AB - We report a novel cytoplasmic male sterility (CMS) system in Brassica juncea
(oilseed mustard) which could be used for production of hybrid seed in the crop.
A male sterile plant identified in a microspore derived doubled haploid
population of re-synthesized B. napus line ISN 706 was found to be a CMS as the
trait was inherited from the female parent. This CMS, designated '126-1', was
subsequently transferred to ten different B. juncea varieties and lines through
inter-specific crosses followed by recurrent backcrossing. The F(1)s of inter
specific crosses were invariably partially fertile, but irrespective of the
variety/line used, the recipient lines became progressively male sterile over
five to seven generations and could be maintained by crossing the male sterile
lines with their normal counterparts. The male sterile lines were found to be
stable for the trait under both long and short day conditions. CMS lines when
crossed with lines other than the respective maintainer line were restored for
fertility, implying that any variety could act as a restorer for '126-1'
cytoplasm in B. juncea. These unique features in maintenance and restoration of
CMS lines coupled with near normal floral morphology of the CMS lines have
allowed the use of '126-1' cytoplasm for hybrid seed production. The uniqueness
of '126-1' has been further established by Southern hybridization with
mitochondrial DNA probes and by a histological study of the development of male
sterile anthers.
PMID- 17036219
TI - Genetic mapping of seed shape in three populations of recombinant inbred lines of
soybean (Glycine max L. Merr.).
AB - Round soybean seeds are sought-after for food-type soybean. Also the genetic
control of seed geometry is of scientific interest. The objectives of this study
were to estimate heritability and map quantitative trait loci (QTLs) responsible
for seed shape traits. Three densely mapped recombinant inbred populations each
with 192 segregants were used, Minsoy x Archer, Minsoy x Noir1, and Noir1 x
Archer. A two rep two location experiment was conducted in Los Andes, Chile, and
East Lansing, MI, USA. Seed height (SH), width (SW), length (SL), and seed volume
(SV) as width x height x length were measured to determine seed shape.
Heritability was estimated by variance component analysis. A total of 19
significant QTLs (LOD >or= 3.7) in ten linkage groups (LG) were detected for all
the traits. Only one QTL was stable across populations and environments and six
were stable in at least two populations in both environments. The amount of
phenotypic variation explained by a single QTL varied from 7.5% for SH, to 18.5%
for SW and at least 30% of the genetic variation for the traits is controlled by
four QTL or less. All traits were highly correlated with each other in all
populations with values ranging from 0.5 to 0.9, except for SL and SW that were
not significantly correlated or had a low correlation in all populations. Narrow
sense heritabilities for all traits ranged from 0.42 to 0.88. We note that LG u9,
u11, and u14 are hot points of the genome for QTLs for various traits. The number
and genomic distribution of the QTLs confirms the complex genetic control of seed
shape. Transgressive segregation was observed for all traits suggesting that
careful selection of parents with similar phenotypes but different genotypes
using molecular markers can result in desirable transgressive segregants.
PMID- 17036216
TI - Influence of sympathetic nervous system on sensorimotor function: whiplash
associated disorders (WAD) as a model.
AB - There is increasing interest about the possible involvement of the sympathetic
nervous system (SNS) in initiation and maintenance of chronic muscle pain
syndromes of different aetiology. Epidemiological data show that stresses of
different nature, e.g. work-related, psychosocial, etc., typically characterised
by SNS activation, may be a co-factor in the development of the pain syndrome
and/or negatively affect its time course. In spite of their clear traumatic
origin, whiplash associated disorders (WAD) appear to share many common features
with other chronic pain syndromes affecting the musculo-skeletal system. These
features do not only include symptoms, like type of pain or sensory and motor
dysfunctions, but possibly also some of the pathophysiological mechanisms that
may concur to establish the chronic pain syndrome. This review focuses on WAD,
particular emphasis being devoted to sensorimotor symptoms, and on the actions
exerted by the sympathetic system at muscle level. Besides its well-known action
on muscle blood flow, the SNS is able to affect the contractility of muscle
fibres, to modulate the proprioceptive information arising from the muscle
spindle receptors and, under certain conditions, to modulate nociceptive
information. Furthermore, the activity of the SNS itself is in turn affected by
muscle conditions, such as its current state of activity, fatigue and pain
signals originating in the muscle. The possible involvement of the SNS in the
development of WAD is discussed in light of the several positive feedback loops
in which it is implicated.
PMID- 17036220
TI - Resin composites: strength of the bond to dentin versus mechanical properties.
AB - This study (1) investigated whether the combination of an adhesive system from
one manufacturer with a resin composite from the same manufacturer provides
superior bonding of the resin composite to dentin compared with the combination
of an adhesive system from one manufacturer with a resin composite from another
manufacturer, and (2) tested for a possible influence on bond strength of
mechanical properties of the resin composite. After application of an adhesive
system, a resin composite was bonded to flattened human dentin and tested in
shear after 1 week. Five adhesive systems (AdheSE, Adper Prompt L-Pop, Clearfil
SE Bond, Optibond Solo Plus, and Xeno III) were tested with each of five resin
composites (Tetric Ceram, Filtek Supreme, Clearfil AP-X, Premise, and EsthetX).
The mechanical properties flexural strength and flexural modulus were determined
by three-point loading. Bond strengths were influenced by the brand of adhesive
system (P < 0.0001) and by the brand of resin composite (P < 0.0001), but the
combination of an adhesive system from one manufacturer with a resin composite
from the same manufacturer did not provide bond strengths that were superior to
those obtained when an adhesive system from one manufacturer was combined with a
resin composite from another manufacturer. Independent of the brand of resin
composite, the adhesive system Clearfil SE Bond mediated the highest bond
strength to dentin. For each adhesive system, the resin composite Clearfil AP-X
resulted in the highest bond strength to dentin. Significant positive
correlations were found between bond strength and flexural strength (P < 0.0026,
r = 0.21) and between bond strength and flexural modulus (P < 0.0017, r = 0.22).
PMID- 17036221
TI - Successful engraftment of mismatched unrelated cord blood transplantation
following reduced intensity preparative regimen using fludarabine and busulfan.
AB - We conducted a pilot study to evaluate the feasibility of reduced-intensity cord
blood transplantation (RI-CBT) using a non-total body irradiation (TBI) regimen
in adult patients with advanced hematologic malignancies. Seventeen patients with
a median age of 58 years (range, 38-74) underwent RI-CBT at Tsukuba Memorial
Hospital between April 2004 and November 2005. Preparative regimens were
fludarabine 30 mg/m(2) for 6 days, and busulfan 4 mg/kg for 2 days. Tacrolimus
was used for prophylaxis of graft-vs-host disease (GVHD). Median numbers of
infused total nucleated were 2.6 x 10(7)/kg (range, 2.0-3.3). HLA disparity was
found in 2/6 antigens (n=16) and 1/6 antigens (n=1). Underlying diseases
progressed despite preparative regimens in four patients. Of the remaining 13
patients, nine patients achieved engraftment at a median of day 18 (range, 17
28). Six of the nine patients with engraftment achieved complete donor-type
chimerism by day 100. Six patients were alive in remission at median follow-up of
13.1 months (range, 1.0-19.0). This study demonstrated the feasibility of RI-CBT
using a non-TBI regimen in adults. When disease progression is controlled by the
preparative regimen, RI-CBT carries a clinically significant graft-vs-tumor
effect. Further studies are required to identify patients who benefit from this
regimen.
PMID- 17036222
TI - The use of combined lateral and medial releases in the treatment of post
traumatic contracture of the elbow.
AB - Elbow stiffness is a common disorder, which restricts daily activities. Between
30 degrees and 130 degrees of elbow movement is usually enough to perform most
daily activities. However, a 10 degrees to 15 degrees loss of elbow extension may
be a problem when the patient is an athlete. From 1996 to 2004, 20 elbows of 20
patients (who were available for follow-up examination) were treated by lateral
and medial release at Kocaeli University, for post-traumatic elbow contracture.
Preoperative and the postoperative 12-month follow-up measurements were
performed. The mean preoperative arc of motion was 35 degrees and this value
improved to 86.2 degrees . The maximum improvement at the arc of motion was 105
degrees . In an effort to understand the pathophysiology of the condition,
surgical approaches may be used safely. The purpose of this study was to assess
the functional outcome of the elbow joint after using a combination of lateral
and medial approaches to treat elbow stiffness.
PMID- 17036223
TI - Dynamic hip screw in the treatment of intertrochanteric fractures: a comparison
of two fixation methods.
AB - The study is a prospective evaluation and comparison. A minimally invasive
Dynamic Hip Screw (MIDHS) technique is presented. One hundred and two patients
with intertrochanteric fractures were treated with either a MIDHS or a
conventional dynamic hip screw (CDHS). We used the Singh index as a measure of
osteoporosis and also classified the fractures according to three different
systems (OTA, Boyd-Griffin, and Evans). All patients were followed up for 12
months with a hip score evaluation. The patients were divided into two groups,
based on the method of treatment. The MIDHS group includes 42 patients with an
average age of 72.6 years. The CDHS group includes 60 patients, with an average
age of 71.3 years. Both groups were similar in injury mechanism, fracture types,
mean Singh index and confounding medical condition (all p values >0.05). The CDHS
group had significantly larger wound incision, greater haemoglobin level drop,
higher pain level, more total analgaesic use and longer hospital stay than the
MIDHS group (all p values<0.05). The hip score, union rate, healing time,
adequate reduction and adequate screw position rate was not significantly
different between the two groups (all p values >0.05). In conclusion, either a
MIDHS or a CDHS in the treatment of intertrochanteric fractures is an effective,
simple and safe method. The mini-invasive technique as opposed to the
conventional technique has smaller wound size, lower pain level, and lower blood
loss. Hospital stay and total analgaesic use were decreased, benefitting the
patient and reducing hospital cost.
PMID- 17036225
TI - Complementary and alternative medicines for use in supportive care in pediatric
cancer.
AB - INTRODUCTION: Complementary and alternative medical practices (CAM) are being
used by increasing numbers of children with cancer. DISCUSSION: Recent surveys
report CAM use prevalence rates of 24-90% in children with cancer. Interest in
supporting children through the side effects or stress of conventional treatment
has been described as one of the major motivating factors for the use of CAM
therapies. Research is difficult secondary to the complexity of the therapies and
lack of standardization. However, several research studies investigating CAM
therapies for supportive care in children with cancer are ongoing. Information on
several studies in progress through the Children's Oncology Group and other
institutions will be reviewed. CONCLUSION: The progress made in the development
of these studies demonstrates that CAM therapies can be investigated for their
supportive care roles in the therapy of children with cancer.
PMID- 17036224
TI - Intraoperative electrostimulation objectifies the assessment of functional nerve
preservation after mesorectal excision.
AB - BACKGROUND: To improve nerve-sparing surgery, intraoperative electrical
stimulation of pelvic autonomic nerves (INS) has been proposed in urology,
gynecology, and visceral surgery. The aim of this study was to assess the impact
of INS while monitoring intravesical pressure on the accurate evaluation of
pelvic autonomic nerve preservation (PANP) after mesorectal excision. It was
sought to determine whether this confirmation is useful in the prediction of
postoperative urinary function. METHODS: Sixty-two patients with mesorectal
exzision for rectal cancer were examined prospectively. PANP was assessed
visually by the surgeon and with INS. Bladder function was evaluated by post
voiding residual volume measurement, rate of recatheterization, rate of long-term
urinary catheterisation, and the international prostatic symptom score with
quality of life index. RESULTS: INS confirmed bilateral preservation of
parasympathetic nerves in 46 patients (74%), and in 10 patients (16%) in at least
one side. In six patients (10%), INS failed to confirm PANP. Eleven patients
(18%) developed urinary symptoms postoperatively. INS results had a higher
sensitivity than visual assessment by the surgeon (82 vs 46%). Values for
specificity ranged at 90 and 92%, respectively. Accuracy of INS in predicting
PANP was higher (88 vs 83%). The correlation between urinary function and the
findings on INS was good (kappa-value: 0.65), correlation between urinary
function and visual assessment by the surgeon was fair (kappa-value: 0.40).
CONCLUSION: INS, while monitoring intravesical pressure, accurately predicts
bladder function after mesorectal excision. It may provide further insight into
pelvic autonomic nerve sparing techniques.
PMID- 17036226
TI - Does granulocyte transfusion play a role in the multidisciplinary treatment of
invasive mycosis?
PMID- 17036227
TI - Early thermal history significantly affects the seasonal hyperplastic process
occurring in the myotomal white muscle of Dicentrarchus labrax juveniles.
AB - The effect of early (embryonic and larval) thermal history on subsequent
(juvenile) white muscle hyperplasia was studied in a teleost fish, the European
sea bass (Dicentrarchus labrax L.). D. labrax, incubated and reared at constant
temperatures of 13 degrees C, 15 degrees C or 20 degrees C from the embryonic
stage of half epiboly up to 18-19 mm in total length, were transferred to ambient
seawater temperature and reared for the subsequent 14 months on commercial feed.
The somatic growth of juveniles was linked to annual variations of ambient
seawater temperature and inversely related to early rearing temperature, so that,
after 14 months, the juveniles originally reared at low temperatures had
compensated for the growth retardation experienced during early life. The white
muscle growth process of juveniles was quantified after two periods of growth
opportunity at ambient seawater temperature (100 and 400 days post-transfer) as
well as, in order to follow total-length-dependent effects of early temperature
and to discriminate total-length-independent effects of early temperature, on
juveniles from the three batches sampled at six successive equivalent total
lengths (31-33, 84-88, 141-145, 166-172, 196-206 and 211-220 mm). Our data
demonstrate the existence of a seasonal recruitment of new white muscle fibres
when seawater temperature increases and of a shrinkage of the largest white
muscle fibres during the winter months. The seasonal recruitment of new white
muscle fibres occurring in juveniles is linked to their early rearing
temperature. Juveniles originating from low temperatures have a higher and longer
capacity to recruit new white muscle fibres when seawater temperature increases,
supporting their better somatic growth. This finding is discussed in relation to
the early (embryonic and larval) myogenic processes of the three populations and
is related to their sex ratio.
PMID- 17036228
TI - Association between the muscle-specific proteins desmin and caveolin-3 in muscle
cells.
AB - The muscle-specific intermediate filament protein desmin is expressed in
mononucleated myoblasts and in differentiated myotubes. Desmin has been shown to
associate with the sarcolemma in specific structures, such as neuromuscular
junctions and the dystrophin-associated protein complex. Since these are
specialized membrane regions, the study of a possible association between desmin
and liquid-ordered membrane microdomains is of particular interest. We have
carried out an analysis of the association between desmin and the muscle-specific
protein caveolin-3, a major component of caveolar microdomains. Our results
demonstrate that (1) desmin precisely co-localizes with caveolin-3 in myoblasts
and multinucleated myotubes, (2) caveolin-3 is up-regulated during in vitro chick
muscle development, (3) desmin is detectable in caveolae-enriched membrane
fractions prepared from skeletal muscle, and (4) caveolin-3 co-immunoprecipitates
with desmin. We have thus shown, for the first time, an association between the
intermediate filament protein desmin and caveolin-3 in myogenic cells.
PMID- 17036229
TI - Differential expression of several molecules of the extracellular matrix in
functionally and developmentally distinct regions of rat spinal cord.
AB - We have examined the regional distribution of several chondroitin sulfate
proteoglycans (neurocan, brevican, versican, aggrecan, phosphacan), of their
glycosaminoglycan moieties, and of tenascin-R in the spinal cord of adult rat.
The relationships of these molecules with glial and neuronal populations,
identified with appropriate markers, were investigated by using multiple
fluorescence labeling combined with confocal microscopy. The results showed that
the distribution of the examined molecules was similar at all spinal cord levels
but displayed area-specific differences along the dorso-ventral axis, delimiting
functionally and developmentally distinct areas. In the gray matter, laminae I
and II lacked perineuronal nets (PNNs) of extracellular matrix and contained low
levels of chondroitin sulfate glycosaminoglycans (CS-GAGs), brevican, and
tenascin-R, possibly favoring the maintenance of local neuroplastic properties.
Conversely, CS-GAGs, brevican, and phosphacan were abundant, with numerous thick
PNNs, in laminae III-VIII and X. Motor neurons (lamina IX) were surrounded by
PNNs that contained all molecules investigated but displayed various amounts of
CS-GAGs. Double-labeling experiments showed that the presence of PNNs could not
be unequivocally related to specific classes of neurons, such as motor neurons or
interneurons identified by their expression of calcium-binding proteins
(parvalbumin, calbindin, calretinin). However, a good correlation was found
between PNNs rich in CS-GAGs and the neuronal expression of the Kv3.1b subunit of
the potassium channel, a marker of fast-firing neurons. This observation confirms
the correlation between the electrophysiological properties of these neurons and
the specific composition of their microenvironment.
PMID- 17036230
TI - Ontogeny of the GnRH systems in zebrafish brain: in situ hybridization and
promoter-reporter expression analyses in intact animals.
AB - The ontogeny of two gonadotropin-releasing-hormone (GnRH) systems, salmon GnRH
(sGnRH) and chicken GnRH-II (cGnRH-II), was investigated in zebrafish (Danio
rerio). In situ hybridization (ISH) first detected sGnRH mRNA-expressing cells at
1 day post-fertilization (pf) anterior to the developing olfactory organs.
Subsequently, cells were seen along the ventral olfactory organs and the
olfactory bulbs, reaching the terminal nerve (TN) ganglion at 5-6 days pf. Some
cells were detected passing posteriorly through the ventral telencephalon (10-25
days pf), and by 25-30 days pf, sGnRH cells were found in the
hypothalamic/preoptic area. Continuous documentation in live zebrafish was
achieved by a promoter-reporter expression system. The expression of enhanced
green fluorescent protein (EGFP) driven by the sGnRH promoter allowed the earlier
detection of cells and projections and the migration of sGnRH neurons. This
expression system revealed that long leading processes, presumably axons,
preceded the migration of the sGnRH neuron somata. cGnRH-II mRNA expressing cells
were initially detected (1 day pf) by ISH analysis at lateral aspects of the
midbrain and later on (starting at 5 days pf) at the midline of the midbrain
tegmentum. Detection of red fluorescent protein (DsRed) driven by the cGnRH-II
promoter confirmed the midbrain expression domain and identified specific
hindbrain and forebrain cGnRH-II-cells that were not identified by ISH. The
forebrain DsRed-expressing cells seemed to emerge from the same site as the sGnRH
EGFP-expressing cells, as revealed by co-injection of both constructs. These
studies indicate that zebrafish TN and hypothalamic sGnRH cell populations share
a common embryonic origin and migratory path, and that midbrain cGnRH-II cells
originate within the midbrain.
PMID- 17036231
TI - Block of mitochondrial apoptotic pathways in lizard ovarian follicle cells as an
adaptation to their nurse function.
AB - Pyriforms are ovarian follicle nurse cells that undergo apoptosis at the end of
previtellogenesis and are completely eliminated by the epithelium. This event is
accompanied by the active transfer of organelles and macromolecules to the oocyte
via an intercellular bridge. Since it would be a nonsense for damaged
mitochondria to reach the oocyte, we have postulated that pyriform cells have
adapted their apoptotic machinery to prevent mitochondrial degradation. To verify
this hypothesis, we have studied mitochondrial morphology and functionality
during follicle cell regression. Cytological and biochemical evidence indicates
that mitochondria in pyriforms maintain their size, organization and membrane
potential. This clearly indicates that they are not involved in apoptosis
signalling/progression. This block would favour both the oocyte, by increasing
the pool of organelles available from follicle cells, and also the regressing
pyriforms, by maintaining the energy resources required for completion of their
nurse function. The block is probably attributable to an over-expression of Bcl-2
and might be carried out by sequestering cytochrome c inside the organelles. As
demonstrated by in vitro experiments, the mitochondrial apoptosis pathway can be
activated by stress induction, such as serum deprivation, but not following
physiological pro-apoptotic signalling, such as treatment with gonadotrophin
releasing hormone.
PMID- 17036232
TI - Customized imaging for children and obese people: key issues and strategies.
PMID- 17036233
TI - [The influence of proprioceptive insoles (Bourdiol) on the sagittal curvature and
inclination of the trunk].
AB - Proprioceptive insoles rely on the concept of Rene-Jaques Bourdiol, a French
neurologist. The aim is to modulate plantar surface sensibility and to influence
posture and statics of patients: it is hypothesized that the effect of modified
afferent sensory input through proprioceptive stimulation of terminal muscle
chains will have either a relaxing or stimulating effect on the whole body, which
may be realized by affecting the posture. Small pads with a thickness of
typically 1-3 mm are embedded into the insole to provide a specific stimulation.
In fitting the insoles selectively to the individual patient the effect of the
insoles on the trunk posture is taken as a feedback. This study investigates the
influence of proprioceptive insoles on the sagittal curve in 20 selected
patients. The protocol used a repeated measures research design. The measures of
the sagittal curve were obtained using raster stereography. The four different
conditions were: (1) barefoot, (2) convenient shoes without the insoles, (3) the
same shoes with a placebo insole, and (4) the same shoes with neurological
insoles. Evaluation of raster stereographs provided the kyphotic angle between T4
and T12 and lordotic angle between T12 and S1. Statistical evaluation was
performed with the t-test for paired measurements. No significant differences
were found in the sagittal profile. Only trunk inclination in normal posture was
found to yield a significant difference (0.38 degrees) between placebo and
neurological insoles. However, no clear statement on the efficiency of
neurological insoles can be made.
PMID- 17036234
TI - [Significance of microbial colonisation in materials for orthopaedic technology.
New insights].
AB - A great problem in the treatment of diabetes are infections of diabetic feet. A
likely reservoir of microorganisms are contaminated orthopaedic materials.
Insoles from 70 patients were examined for potential microbial colonisation.
Commonly employed materials were contaminated in vitro under standardised
conditions using known microorganisms. After treating with an alcoholic skin
disinfectant, the organisms were counted semiquantitatively. In addition to
pathogens, the surfaces showed mainly microorganisms present in the normal skin
flora. In all materials tested, disinfection reduced the number of organisms by 4
5 log orders. It could be shown that simple disinfection (wiping) reduces the
microorganisms present on orthopaedic materials to an acceptable number. Further
studies are needed to determine whether this also reduces the incidence of
diabetic skin and soft tissue infection.
PMID- 17036236
TI - Localized basal meningeal enhancement in tuberculous meningitis.
AB - BACKGROUND: Focal basal meningeal enhancement may produce a confusing CT picture
in children with suspected tuberculous meningitis (TBM). OBJECTIVE: To
demonstrate the incidence, distribution and appearance of localized basal
meningeal enhancement in children with TBM. MATERIALS AND METHODS: CT scans of
patients with definite (culture proven) and probable (CSF suggestive) TBM were
retrospectively evaluated by two observers. Localized basal enhancement was
documented as involving: unilateral cistern of the lateral fossa (CLF),
unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination,
unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern
and isolated quadrigeminal plate cistern. RESULTS: The study included 130
patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement
was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly,
followed by the lateral fossa cistern. The ambient cistern was involved in three
patients and the quadrigeminal plate cistern in one. Focal areas of enhancement
corresponded to the areas of infarction in every patient. CONCLUSION: Focal basal
meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in
mind when evaluating CT scans in children presenting with focal neurological
findings, seizures or meningism in communities where TBM is endemic.
PMID- 17036235
TI - Using multidetector-row CT in neonates with complex congenital heart disease to
replace diagnostic cardiac catheterization for anatomical investigation: initial
experiences in technical and clinical feasibility.
AB - BACKGROUND: Echocardiography is the first-line modality for the investigation of
neonatal congenital heart disease. Diagnostic cardiac catheterization, which has
a small but recognized risk, is usually performed if echocardiography fails to
provide a confident evaluation of the lesions. OBJECTIVE: To verify the technical
and clinical feasibilities of replacing diagnostic cardiac catheterization with
multidetector-row CT (MDCT) in neonatal complex congenital heart disease.
MATERIALS AND METHODS: Over a 1-year period we prospectively enrolled all
neonates with complex congenital heart disease referred for diagnostic cardiac
catheterization after initial assessment by echocardiography. MDCT was performed
using a 40-detector-row CT scanner with dual syringe injection. A
multidisciplinary congenital heart disease team evaluated the MDCT images and
decided if further diagnostic cardiac catheterization was necessary. The accuracy
of MDCT in detecting separate cardiovascular anomalies and bolus geometry of
contrast enhancement were calculated. RESULTS: A total of 14 neonates were
included in the study. No further diagnostic cardiac catheterization was needed
in any neonate. The accuracy of MDCT in diagnosing separate cardiovascular
anomalies was 98% (53/54) with only one atrial septal defect missed in a patient
with coarctation syndrome. The average cardiovascular enhancement in evaluated
chambers was 471 HU. No obvious beam-hardening artefact was observed. CONCLUSION:
The technical and clinical feasibility of MDCT in complex congenital heart
disease in neonates is confirmed. After initial assessment with echocardiography,
MDCT could probably replace diagnostic cardiac catheterization for further
anatomical clarification in neonates.
PMID- 17036237
TI - Prenatal MR imaging of a meconium pseudocyst extending to the right subphrenic
space with right lung compression.
AB - Meconium pseudocyst results from a loculated inflammation occurring in response
to spillage of meconium into the peritoneal cavity after a bowel perforation.
Certain cystic lesions, such as abscesses and dermoid and epidermoid cysts, are
known to show reduced water diffusion on DWI. MRI has recently become a valuable
adjunct to ultrasonography for fetal gastrointestinal anomalies. Complementary to
ultrasonography, prenatal MRI can help further characterize the lesion and can
clearly demonstrate the anatomical relationship between the lesion and adjacent
organs. We report a case of meconium pseudocyst that was prenatally imaged with
ultrasonography and MRI, postnatally complicated by pneumoperitoneum, and proved
by postnatal surgery and histopathology. We emphasize the MRI of the pseudocyst,
particularly T1-weighted and diffusion-weighted imaging.
PMID- 17036243
TI - Familial amyotrophic lateral sclerosis: a SOD1-unrelated Japanese family of
bulbar type with Bunina bodies and ubiquitin-positive skein-like inclusions in
lower motor neurons.
AB - We describe a new family with adult onset amyotrophic lateral sclerosis (FALS),
in which the disease was characterized clinically by relatively rapid progression
of bulbar symptoms. Gene analysis of Cu/Zn superoxide dismutase (SOD1) performed
in one patient showed no mutations. Autopsy of another patient demonstrated
degenerative changes restricted to the upper and lower motor neuron systems; no
evident changes were observed in the posterior column, Clarke's column or
spinocerebellar tracts. The presence of Bunina bodies and ubiquitin-positive
skein-like inclusions in the lower motor neuron was of considerable interest.
Cases of FALS with such pathological features are quite rare in the literature.
Identification of the gene responsible for the disease is desirable in order to
shed further light on the molecular pathology of not only familial, but also
sporadic, ALS.
PMID- 17036244
TI - Assessing the cognitive impact of Alzheimer disease pathology and vascular burden
in the aging brain: the Geneva experience.
AB - The progressive development of Alzheimer disease (AD)-related lesions, such as
neurofibrillary tangles (NFT), amyloid deposits and synaptic loss, and the
occurrence of microvascular and small macrovascular pathology within the cerebral
cortex are conspicuous neuropathologic features of brain aging. Recent
neuropathologic studies strongly suggested that the clinical diagnosis of
dementia depends more on the severity and topography of pathological changes than
on the presence of a qualitative marker. However, several methodological
problems, such as selection biases, case-control design, density-based measures
and masking effects, of concomitant pathologies persisted. In recent years, we
performed several clinicopathologic studies using stereological counting of AD
lesions. In order to define the cognitive impact of lacunes and microvascular
lesions, we also analyzed pure vascular cases without substantial AD pathology.
Our data revealed that total NFT numbers in the CA1 field, cortical microinfarcts
and subcortical gray matter lacunes were the stronger determinants of dementia.
In contrast, the contribution of periventricular and subcortical white matter
demyelinations had a modest cognitive effect even in rare cases with isolated
microvascular pathology. Importantly, in cases with pure AD pathology, more than
50% of Clinical Dementia Rating scale variability was not explained by NFT,
amyloid deposits and neuronal loss in the hippocampal formation. In cases with
microvascular pathology or lacunes, this percentage was even lower. The present
review summarizes our data in this field and discusses their relevance within the
theoretical framework of the functional neuropathology of brain aging and with
particular reference to the current efforts to develop standardized
neuropathological criteria for mixed dementia.
PMID- 17036245
TI - Parasite diversity of sticklebacks from the Baltic Sea.
AB - In the brackish Baltic Sea, the species richness and diversity of parasite
communities of three- (Gasterosteus aculeatus) and nine-spined sticklebacks
(Pungitius pungitius) were investigated. The studies regarded four localities at
the Schleswig-Holstein and Mecklenburg coasts, northern Germany, where salinities
were between 10 and 18 per thousand. Species richness was relatively high,
attaining 15 parasite species in G. aculeatus and 16 in P. pungitius, which are
only surpassed by former investigations that lasted a year or more. An analysis
of parasite species identity revealed clear differences in diverse localities
referring to different supracommunities. The infracommunity comprised maximally
of eight species in G. aculeatus and seven in P. pungitius, which corresponds to
former investigations. The mean value of infracommunity with 5.3 parasites is the
highest value ever found in small-sized fish. An infracommunity index revealed
that the digenean Podocotyle atomon and Magnibursatus caudofilamentosa and the
copepod Thersitina gasterostei were the most abundant parasites. The relationship
of component community to mean infracommunity can judge about the threshold
level, which allows parasite to settle successfully. An important factor to form
parasite communities is the season of their appearance, which depends also on
their reproduction and on the presence of intermediate hosts. In addition, the
choice of prey (for passive infection) and quality of habitats (for active
infection) influences the constitution of the parasite communities. The diversity
values of parasites were low in all hosts, which is due to the brackish milieu
and by different levels of eutrophication, which both create extreme
environments. These do not mirror in every case the biodiversity of the
respective habitats. The parasite community was in a level of early heterotrophic
succession where low diversity is combined with high population density, which is
characteristic for extreme environments. Therefore, intraspecific competition
dominates and niches are wide. Under this aspect and regard of the actually valid
definition that niches are dynamic systems between organisms and environment, the
theory of vacant niches of some authors can be rejected.
PMID- 17036246
TI - Special issue dedicated to Bodo Christ.
PMID- 17036247
TI - [Relaparoscopy as an alternative to laparotomy for laparoscopic complications].
AB - In the field of visceral surgery, complications requiring reintervention
following laparoscopy are currently most likely to be approached with
conventional laparotomy. However, relaparoscopy has the theoretical advantage of
maintaining the reduced morbidity allowed by the first procedure. Essential to
the success of relaparoscopy is a clear understanding of the various specific
complications. Should the surgeon decide on relaparoscopy, then prompt action is
of central importance. Following laparoscopic cholecystectomy, it is
fundamentally technically possible through renewed laparoscopy to treat not only
subhepatic abscesses but also smaller lesions of the bile duct, for example from
the gall bladder fossa. Revision of complications following fundoplication is
technically very demanding and should be performed only by those most experienced
in the techniques of laparoscopy. In contrast to interventional drainage,
relaparoscopy of abscesses following laparoscopic appendectomy has the
theoretical advantage of allowing recognition and treatment of the causes, for
example in the case of appendicular stump insufficiency. Relapses very shortly
after endoscopic surgery of inguinal herniae result from erroneous technique and
may be corrected endoscopically in most cases. Complications following colon
surgery have so far been dealt with using open surgery for technical reasons and
also for patient safety. Given the uncertainty in the literature, patient safety
must be paramount, when deciding on which technique is best to employ,
particularly in cases of haemorrhage.
PMID- 17036248
TI - [PTA and stent placement distal to the superficial femoral artery].
AB - Although angioplasty and stent applications in the iliac vessels and the
superficial femoral artery have become routine procedures, their usefulness for
the treatment of lesions of the popliteal artery and the lower leg arteries is
still under discussion. For the popliteal artery, limitations are mainly due to
the high mechanical stress in this area, causing high traction forces. Moreover,
beyond the occlusive atherosclerotic changes, specific pathological entities such
as aneurysms, emboli, entrapment syndromes, and cystic adventitial disease have
to be differentiated. There is hope that the development of innovative stent
designs with high flexibility might overcome the limitations. For lesions of the
lower leg arteries treatment with percutaneous transluminal angioplasty (PTA) has
become the method of choice. However, stent designs as used for cardiac
interventions have been adapted for their application below the knee, and first
encouraging results may help to justify their broad use in the future. Regarding
PTA, innovative equipment and techniques for the treatment of arterial lesions
below the knee include dedicated, long, and very flexible balloons, cutting
balloon cryoplasty, and laser angioplasty. Regarding stents, bare metal stents,
stents with passive or active coatings, and bioabsorbable stents have all been
successfully used.
PMID- 17036249
TI - [The side effects of antiretroviral therapy].
AB - The introduction of highly active antiretroviral therapy (HAART) has resulted in
tremendous improvements in morbidity and mortality in HIV-infected patients.
However, the use of these drugs has coincided with an increasing number of
reports of gastrointestinal, hepatic or metabolic side effects. Soon after
beginning antiretroviral treatment drug rashes, hypersensitivity reactions,
immune reconstitution syndrome or injection site reaction are frequently seen.
Under HAART dyslipidemia, impaired glucose metabolism and elevated liver function
are observed. In the later treatment phase, lipodystrophy, a combination of
peripheral lipoatrophy and central fat accumulation, occurs.
PMID- 17036250
TI - [HIV-associated tumors].
AB - In the beginning of the HIV epidemic, Kaposi sarcoma was a common stigma in AIDS
patients and one of the leading causes of death. While Kaposi sarcoma is seen
less frequently since the introduction of antiretroviral therapy, lymphoma and
other malignancies are an increasing therapeutic challenge. The incidence of HPV
related anal carcinoma and its precursor lesions is rising so dramatically that
screening programs as they are already established for cervical carcinoma should
be implemented. The role of HPV in UV-associated tumors is not yet determined.
Additional risk factors like smoking and HCV co-infection seem to play important
roles in the high incidence of lung and hepatocellular carcinomas. While fewer
patients die from opportunistic infections, we face a growing problem with
malignancies in HIV-positive patients.
PMID- 17036252
TI - The impact of mental illness on quality of life: A comparison of severe mental
illness, common mental disorder and healthy population samples.
AB - Patient-centred outcomes such as quality of life (QOL) are valued and used
extensively in mental healthcare evaluations, but concerns remain about their
practical application due to perceived measurement issues, including
responsiveness and relationships with objective indicators and depression.
Evidence from general population studies challenge some assumptions, suggesting
that measurement difficulties might relate to the characteristics of mental
health samples, rather than measurement itself. This paper assesses the impact of
mental illness on QOL and its measurement, examining whether the life-conditions,
opportunities and QOL of different mental health-status groups vary, and if
explanatory models of domain-specific and global QOL differ. Objective life
conditions, access to life-opportunities and subjective QOL were assessed over 2
years, using the same methodology in severe mental illness (SMI; n = 149
(baseline)/n = 126 (follow-up)), common mental disorder (CMD; n = 794/354) and no
disorder (n = 1119/583) groups. Objective life-conditions were worse in the SMI
group than in mentally healthy population and CMD groups, but the opportunities
available to the SMI group were no more restricted than the CMD group. Subjective
QOL ratings reflected this; SMI group scores were lower than the healthy
population and in some life-domains the CMD group. Models of QOL suggested that
life-quality was explained differently in the three groups. QOL studies combining
mental health samples should control for health-status group, and domain-specific
and global indicators of lifestyle and opportunity.
PMID- 17036254
TI - Psychometric properties of the Japanese version of the Quality Of Life-Cancer
Survivors Instrument.
AB - The purpose of this study was to describe the psychometric properties of the
Japanese version of the Quality of Life-Cancer Survivors Instrument (QOL-CS-J)
developed in the U.S. This study was conducted as a mail survey to survivors of
more than 5 years post curative resection for non-small-cell lung cancer (NSCLC)
and who had participated in an earlier survey. This survey included the medical
and demographic factors, the QOL-CS scores, and the Medical Outcome Study 36-Item
Short Form (SF-36). A total of 113 survivors completed the survey. To confirm the
reliability, the Cronbach's alpha coefficient of each subscale was calculated as
an internal consistency (alpha = 0.65-0.89). To confirm the validity of the trial
as conducted, Pearson's correlation coefficients between the subscales of the QOL
CS and the subscales of the SF-36 were calculated. There were moderate
correlations between associated subscales including QOL-CS physical to SF-36
bodily pain (r = 0.45) and vitality (r = 0.52), QOL-CS psychological to SF-36
mental health (r = 0.55), QOL-CS social to SF-36 general health perception (r =
0.31) and mental health (r = 0.47), and QOL-CS total to each subscale of SF-36 (r
= 0.25-0.64). Findings demonstrated that the QOL-CS-J adequately measured the QOL
in long-term NSCLC survivors.
PMID- 17036253
TI - Health-related quality of life among disease-free stomach cancer survivors in
Korea.
AB - Previous studies about the quality of life (QOL) in stomach cancer survivors
focused on selected clinical parameters and did not consider the broader
implications for overall health and QOL. We evaluated the impact of demographic
and treatment-related factors on the QOL of stomach cancer survivors. We asked
391 stage I-III stomach cancer survivors who had been disease-free for at least 1
year after surgery to complete a demographic questionnaire, the European
Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, and its
stomach module, QLQ-STO22.Survivors undergoing total gastrectomy reported greater
eating restrictions than those undergoing subtotal gastrectomy. Receiving
chemotherapy or radiotherapy did not significantly affect any QLQ-C30 or QLQ
STO22 scores. Role and emotional functioning improved with increasing age, and
stomach-specific symptoms (pain, eating restrictions, and anxiety) lessened.
Compared with female survivors, male survivors had better physical and role
functioning. Smoking status was also a significant negative predictor of physical
functioning and anxiety. Comorbidities and selected demographic characteristics
had a greater effect than type of treatment on the QOL of post-operative stomach
cancer patients.
PMID- 17036255
TI - A comparison of traditional and Rasch cut points for assessing clinically
important change in health-related quality of life among patients with asthma.
AB - BACKGROUND: Patient-perceived change in health-related quality of life (HRQoL)
domains has often been classified using a 15-point patient transition rating
scale. However, traditional change levels of trivial ( - 1, 0, or 1), minimal (2,
3 or - 2, - 3), moderate (4, 5 or - 4, - 5) and large (6, 7 or - 6, - 7) on this
scale have been arbitrarily defined and originally assumed that change related to
an improvement was the same as that for a decline. OBJECTIVE: To compare
traditional and Rasch partial credit model-derived cut points and the mean
changes for each change categorization when assessing clinically important change
in asthma-specific HRQoL. METHODS: Our sample included 396 asthmatic outpatients
who completed bimonthly telephone interviews on the Asthma Quality of Life
Questionnaire and transition rating items over 1 year of participation. We
employed item response theory in a novel approach to identify cut points on
domain-specific HRQoL change data and transition ratings. After determining
natural cut points for minimal, moderate, and large differences on the transition
rating anchor, we calculated mean changes under change categorizations for both
improvements and declines for the two transition rating classification
approaches. RESULTS: Although traditional and Rasch categorizations for small,
moderate, and large changes slightly differed and displayed a lack of symmetry
between improvements and declines, nearly all mean changes between classification
approaches were comparable. CONCLUSIONS: In this study, traditional transition
rating cut points remain suitable to assess HRQoL clinical significance in
outpatients with asthma.
PMID- 17036256
TI - Assessment of traffic noise pollution from 1989 to 2003 in Lanzhou City.
AB - On the basis of the continuous traffic noise data observed at 142 sites
distributed in 52 roads from 1989 to 2003, the characteristics of traffic noise
and effect factors were analyzed through traffic noise indices, such as Lep, L10,
L50, L90, TNI, and Pn. Our findings allow us to reach a number of conclusions as
follows: Firstly, traffic noise pollution was serious, and its fluctuant
characteristic was obvious, resulting in a great intrusion to public in Lanzhou
City during last 15 years. Secondly, traffic noise made a distinction between
trunk lines and secondary lines, west-east direction roads and north-south
direction roads. Thirdly, spatial character and time rule of traffic noise were
obvious. In addition, traffic volume, traffic composition, road condition, and
traffic management were identified as the key factors influencing traffic noise
in this city.
PMID- 17036257
TI - Monitoring of pesticide residues in fruits.
AB - Fruit samples of ber, grapes and guava analysed for pesticide residues employing
multiresidue analysis by gas liquid chromatography equipped with ECD and NPD
detectors and capillary columns showed contamination with organochlorine,
synthetic pyrethroid and organophosphate insecticides. Among organochlorines,
HCH, DDT and endosulfan were detected in almost all the samples. Residues of HCH
and DDT were maximum in ber followed by grapes and guava where as of endosulfan
were maximum in guava followed by grapes and ber. All the fruit samples showed
the presence of residues with one or the other group of pesticides. Residues of
none of the pesticides exceeded the MRL values in any sample. On the basis of
these studies, it is suggested that monitoring studies should be extended to
other fruits grown in different agro climatic regions which may serve as basis
for future policy in chemical use.
PMID- 17036258
TI - Estimating the rate of poisoning by insecticide-treated seeds in a bird
population.
AB - Poisonings of granivorous birds by cereal seed treatments have been reported in
the UK, but the true frequency of poisonings is unknown. We aimed to measure the
rate of mortality due to poisoning by seed treatments in woodpigeons (Columba
palumbus) in an area of East Anglian farmland where the risk from these compounds
appeared high. Woodpigeons were fitted with temperature-sensing radio-tags and
monitored daily during the winters of 1994/95 and 1995/96. Birds' deaths were
detected and attempts made to retrieve carcasses for post-mortem examination
including, where possible, analysis for pesticide residues. Ninety-one
woodpigeons were monitored. Eleven birds died, but the causes of their deaths
were uncertain: one contained a low residue of insecticide and in the other ten
cases, no carcass was recovered, so no analysis was possible. Therefore, the
number poisoned by pesticides could lie anywhere between zero and eleven. During
1994/95, estimated mortality ranged from 0% to 52%, depending on how many (if
any) of the 11 casualties were poisoned. During 1995/96 there were no casualties.
Using conservative diagnostic rules for classifying birds as poisoned by OP seed
treatments, no link was found between the availability of treated fields in the
study area and the rate of poisonings, and there were no significant differences
between the two study years. For reasons discussed in the paper, true mortality
resulting from exposure to insecticide seed treatments was considered likely to
lie in the range 0-5%.
PMID- 17036259
TI - Brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T are not
associated with response to electroconvulsive therapy in major depressive
disorder.
AB - The aim of the present study was to examine an association of brain-derived
neurotrophic factor (BDNF) polymorphisms G196A and C270T and the response to
electroconvulsive therapy (ECT) in major depressive disorder (MDD). The study
group consisted of 119 patients consecutively admitted for ECT in the Department
of Psychiatry, Tampere University Hospital. All patients fulfilled the diagnostic
criteria of DSM-IV for MDD. ECT was administered three times a week with a brief
pulse constant current device. The Montgomery and Asberg Depression Rating Scale
(MADRS) was used as an outcome measure of depression. Genotyping was performed
using fluorescent allele-specific TaqMan probes. No association between either
G196A or C270T and the response to ECT was found in the whole population. There
were no significant differences in responses between men and women or between
psychotic and non-psychotic patients. However, within subgroups such as in
psychotic and in late-onset depression CC genotype of C270T may predict good
response. BDNF may not be associated with response to ECT in general, but some
association in subgroups may exist.
PMID- 17036260
TI - Deficit of social cognition in subjects with surgically treated frontal lobe
lesions and in subjects affected by schizophrenia.
AB - The ability of humans to predict and explain other people's behaviour by
attributing independent mental states such as desires and beliefs to them, is
considered to be due to our ability to construct a "Theory of Mind". Recently,
several neuroimaging studies have implicated the medial frontal lobes as playing
a critical role in a dedicated "mentalizing" or "Theory of Mind" network in the
human brain. In this study we compare the performance of patients with right and
left medial prefrontal lobe lesions in theory of mind and in social cognition
tasks, with the performance of people with schizophrenia. We report a similar
social cognitive profile between patients with prefrontal lobe lesions and
schizophrenic subjects in terms of understanding of false beliefs, in
understanding social situations and in using tactical strategies. These findings
are relevant for the functional anatomy of "Theory of Mind".
PMID- 17036261
TI - Digestibility of resistant starch containing preparations using two in vitro
models.
AB - BACKGROUND: Resistant starch (RS) is known for potential health benefits in the
human colon. To investigate these positive effects it is important to be able to
predict the amount, and the structure of starch reaching the large intestine. AIM
OF THE STUDY: The aim of this study was to compare two different in vitro models
simulating the digestibility of two RS containing preparations. METHODS: The
substrates, high amylose maize (HAM) containing RS type 2, and retrograded long
chain tapioca maltodextrins (RTmd) containing RS type 3 were in vitro digested
using a batch and a dynamic model, respectively. Both preparations were
characterized before and after digestion by using X-Ray and DSC, and by measuring
their total starch, RS and protein contents. RESULTS: Using both digestion
models, 60-61 g/100 g of RTmd turned out to be indigestible, which is very well
in accordance with 59 g/100 g found in vivo after feeding RTmd to ileostomy
patients. In contrast, dynamic and batch in vitro digestion experiments using HAM
as a substrate led to 58 g/100 g and 66 g/100 g RS recovery. The degradability of
HAM is more affected by differences in experimental parameters compared to RTmd.
The main variations between the two in vitro digestion methods are the enzyme
preparations used, incubation times and mechanical stress exerted on the
substrate. However, for both preparations dynamically digested fractions led to
lower amounts of analytically RS and a lower crystallinity. CONCLUSIONS: The two
in vitro digestion methods used attacked the starch molecules differently, which
influenced starch digestibility of HAM but not of RTmd.
PMID- 17036262
TI - Diet supplementation for 5 weeks with polyphenol-rich cereals improves several
functions and the redox state of mouse leucocytes.
AB - BACKGROUND: Cereals naturally contain a great variety of polyphenols, which exert
a wide range of physiological effects both in vitro and in vivo. Many of their
protective effects, including an improvement of the function and redox state of
immune cells in unhealthy or aged subjects come from their properties as powerful
antioxidant compounds. However, whether cereal-based dietary supplementation
positively affects the immune function and cellular redox state of healthy
subjects remains unclear. AIM OF THE STUDY: To investigate the effects of
supplementation (20% wt/wt) for 5 weeks with four different cereal fractions on
healthy mice. METHODS: Several parameters of function and redox state of
peritoneal leukocytes were measured. The cereals, named B (wheat germ), C
(buckwheat flour), D (fine rice bran) and E (wheat middlings) contained different
amounts of gallic acid, p-hydroxybenzoic acid, vanillic acid, sinapic acid, p
coumaric acid, ferulic acid, quercetin, catechin, rutin and oryzanol as major
polyphenols. RESULTS: In general, all cereal fractions caused an improvement of
the leukocyte parameters studied such as chemotaxis capacity, microbicidal
activity, lymphoproliferative response to mitogens, interleukin-2 (IL-2) and
tumor necrosis factor (TNFalpha) release, as well as oxidized glutathione (GSSG),
GSSG/GSH ratio, catalase (CAT) activity and lipid oxidative damage. We observed
similar effects among the cereal fractions. CONCLUSIONS: The results suggest that
some of these effects may due, at least partially, to the antioxidant activity of
the polyphenols naturally present in cereals. Since an appropriate function of
the leukocytes has been proposed as marker of the health state, a short-term
intake of cereals seems to be sufficient to exert a benefit in the health of the
general population. However, further studies are needed to assess the optimal
doses and to find out which active polyphenols are able to mediate the observed
physiological effects before recommending their regular consumption.
PMID- 17036263
TI - Stigma and discrimination towards people with schizophrenia and their family
members. A qualitative study with focus groups.
AB - BACKGROUND: There is a scarcity of data regarding the actual stigma and
discrimination experienced by schizophrenic patients and their relatives. Those
experiences can vary significantly depending on the specific social group
involved. We have explored such phenomena in our culture with a qualitative
technique. METHODS: We developed a qualitative study with focus groups of
clinically stable schizophrenic outpatients (N = 18) and relatives (N = 26).
Three groups were performed in each sample. RESULTS: Six categories of stigma and
discrimination experiences were extracted from the patients' data: Mental illness
vs. Lack of will, Prejudice related to dangerousness, Over-protection
infantilization, Daily social discrimination, Discrimination in health care,
Descendants, Avoidance-social isolation. Data from relatives were divided into
three sets: discrimination towards the patients witnessed by relatives,
discrimination suffered by the relatives themselves and discrimination exerted by
the relatives on the patients. CONCLUSIONS: Patients and relatives describe a
great variety of stigma and discrimination experiences in all areas of life,
including health care. Isolation and avoidance are common reactions to those
experiences. Publicizing these stigma and discrimination experiences could help
to reduce stigmatizing attitudes in society and result in healthier reactions
from patients, favoring a better course of the illness.
PMID- 17036264
TI - Regional differences in psychiatric disorders in Chile.
AB - BACKGROUND: Psychiatric epidemiological surveys in developing countries are rare
and are frequently conducted in regions that are not necessarily representative
of the entire country. In addition, in large countries with dispersed populations
national rates may have low value for estimating the need for mental health
services and programs. METHODS: The Chile Psychiatric Prevalence Study using the
Composite International Diagnostic Interview was conducted in four distinct
regions of the country on a stratified random sample of 2,978 people. Lifetime
and 12-month prevalence and service utilization rates were estimated. RESULTS:
Significant differences in the rates of major depressive disorder, substance
abuse disorders, non-affective psychosis, and service utilization were found
across the regions. The differential prevalence rates could not be accounted by
socio-demographic differences between sites. CONCLUSIONS: Regional differences
across countries may exist that have both implications for prevalence rates and
service utilization. Planning mental health services for population centers that
span wide geographical areas based on studies conducted in a single region may be
misleading, and may result in areas with high need being underserved.
PMID- 17036265
TI - Help-seeking pathways in early psychosis.
AB - INTRODUCTION: Understanding the help-seeking pathways of patients with a putative
risk of developing psychosis helps improving development of specialised care
services. This study aimed at obtaining information about: type of health
professionals contacted by patients at putative risk for psychosis on their help
seeking pathways; number of contacts; type of symptoms leading to contacts with
health professionals; interval between initial contact and referral to a
specialised outpatient service. METHOD: The help-seeking pathways were assessed
as part of a prospective study in 104 patients with suspected at-risk states for
psychosis. RESULTS: The mean number of contacts prior to referral was 2.38.
Patients with psychotic symptoms more often contacted mental health
professionals, whereas patients with insidious and more unspecific features more
frequently contacted general practitioners (GPs). CONCLUSIONS: GPs have been
found to under-identify the insidious features of emerging psychosis (Simon et
al. (2005) Br J Psychiatry 187:274-281). The fact that they were most often
contacted by patients with exactly these features calls for focussed and
specialised help for primary care physicians. Thus, delays along the help-seeking
pathways may be shortened. This may be of particular relevance for patients with
the deficit syndrome of schizophrenia.
PMID- 17036267
TI - [Manifestation of diffuse proliferative lupus nephritis in a patient treated with
long-term mycophenolate mofetil].
AB - HISTORY AND ADMISSION FINDINGS: A now 34-year old female patient with long
standing systemic lupus erythematosus (SLE) had successfully been treated with
mycophenolate mofetil (MMF) because of former pleuropericardial and pulmonal
lupus manifestations when she was admitted with edema for the first time.
INVESTIGATIONS: Laboratory investigations of urine and blood showed findings
compatible with lupus nephritis. Kidney biopsy revealed lupus nephritis type IV.
TREATMENT AND COURSE: Despite the initiation of cyclophosphamide bolus and
corticosteroid therapy, the kidney function and renal hypertension worsened and
the patient developed cerebral manifestations. Finally, synchronization of
plasmapheresis with subsequent pulse cyclophosphamide led to remission of SLE.
CONCLUSION: Although MMF is a promising innovative agent for induction and
maintenance therapy of lupus nephritis that can be used instead of
cyclophosphamide, there may be cases like the one reported here, in which MMF
cannot prevent lupus flares in first manifestation of severe renal disease.
PMID- 17036268
TI - [Churg-Strauss syndrome--recent developments in diagnosis and treatment].
PMID- 17036270
TI - [Biologicals in the treatment of rheumatic diseases].
PMID- 17036271
TI - [Intra-articular injections of corticosteroids--pro].
PMID- 17036272
TI - [Intra-articular injections of corticosteroids--contra].
PMID- 17036273
TI - [Regulatory T cells in rheumatic diseases].
PMID- 17036274
TI - [Do we need in-patient rheumatology?].
PMID- 17036276
TI - [Therapy of hypertension in the elderly].
PMID- 17036278
TI - [Physician-assisted suicide -- ethical, legal and clinical aspects].
PMID- 17036279
TI - [Cardioverter-defibrillator (ICD) and resynchronization in every patient with
cardiac failure].
PMID- 17036281
TI - Intake of 13C-4 creatine enables simultaneous assessment of creatine and
phosphocreatine pools in human skeletal muscle by 13C MR spectroscopy.
AB - The feasibility of a novel method for the noninvasive and local assessment of
creatine (Cr) and phosphocreatine (PCr) dynamics in human skeletal muscle based
on (13)C magnetic resonance (MR) spectroscopy is presented. A high dose of Cr,
labeled at the guanidino C-4 position with (13)C 11% enrichment, was administered
orally to a human subject for 5 days. Using a surface coil, (13)C MR spectra of
the lower leg were acquired on a 1.5T MR system at regular time intervals during
and after Cr supplementation. An almost twofold increase in the intensities of
the resolved PCr and Cr (13)C-4 signals was observed during this period. The slow
decrease in these signals to normal values after supplementation reflects the
slow daily turnover of Cr. The PCr/Cr ratio did not appear to change over the
whole measurement period. During exercise of the leg, reversible changes in PCr
and Cr signals were observed, reflecting conversion by the Cr kinase reaction.
PMID- 17036282
TI - Water exchange across the erythrocyte plasma membrane studied by HR-MAS NMR
spectroscopy.
AB - Water exchange across the plasma membrane of erythrocytes (red blood cells
(RBCs)) was studied by means of high-resolution magic angle spinning (HR-MAS) NMR
spectroscopy. Under HR-MAS conditions, the centrifugal force causes the splitting
of RBC suspensions into a two-phase system composed of a central core of cell
free water and an outer layer of tightly packed cells. Water belonging to each of
these phases gives rise to two separated resonances. Chemical exchange between
them is not detectable on the chemical shift or saturation transfer (ST) NMR time
scale because of the physical separation between the phases. When the RBCs are
dispersed and immobilized within a matrix made of cross-linked albumin, the
splitting into a two-phase system is prevented and a single exchange-averaged
peak for water is detected in (1)H HR-MAS NMR spectra. The lineshape of this peak
is dependent on transmembrane exchange kinetics, since MAS averages out all the
anisotropic magnetic interactions that are responsible for additional line
broadening under conventional liquid conditions. Line-shape analysis according to
a two-site exchange model yielded a residence lifetime on the order of about 10
ms (at 37 degrees C) for a water molecule within the intracellular compartment,
which is not too far from the generally accepted value of 9.6-14.8 ms.
PMID- 17036283
TI - Magnetic resonance elastography of the lung: technical feasibility.
AB - Magnetic resonance elastography (MRE) is a phase-contrast technique that can
spatially map shear stiffness within tissue-like materials. To date, however, MRE
of the lung has been too technically challenging-primarily because of signal-to
noise ratio (SNR) limitations and phase instability. We describe an approach in
which shear wave propagation is not encoded into the phase of the MR signal of a
material, but rather from the signal arising from a polarized noble gas
encapsulated within. To determine the feasibility of the approach, three
experiments were performed. First, to establish whether shear wave propagation
within lung parenchyma can be visualized with phase-contrast MR techniques, MRE
was performed on excised porcine lungs inflated with room air. Second, a phantom
consisting of open-cell foam filled with thermally polarized (3)He gas was imaged
with MRE to determine whether shear wave propagation can be encoded by the gas.
Third, preliminary evidence of the feasibility of MRE in vivo was obtained by
using a longitudinal driver on the chest of a normal volunteer to generate shear
waves in the lung. The results suggest that MRE in combination with
hyperpolarized noble gases is potentially useful for noninvasively assessing the
regional elastic properties of lung parenchyma, and merits further investigation.
PMID- 17036284
TI - On the origin of apparent low tissue signals in balanced SSFP.
AB - Balanced steady-state free precession (bSSFP) has become increasingly important
in clinical applications. Its signal properties have been investigated over
several years by many groups, and various critical factors for bSSFP signal
intensity and stability, such as off-resonances, flow, and eddy currents, have
been identified. It is generally accepted that bSSFP signal intensity is a
function of relaxation times, excitation angles, and spin densities only. While
this is true for simple phantoms, it appears that signals from tissues are
significantly less intense than predicted by theory. This work demonstrates that
the molecular origin of this apparent signal reduction is due to on-resonance
magnetization transfer (MT). High flip angles in combination with very short
repetition times (TRs), as commonly used for bSSFP, lead to a considerable
saturation in the fraction of macromolecular (MM) pool protons. As a result,
bSSFP signal is strongly attenuated by up to a factor of 2 in the human brain
compared to the signal expected from theory.
PMID- 17036285
TI - Minimally invasive skin rejuvenation with Erbium: YAG laser used in thermal mode.
AB - BACKGROUND AND OBJECTIVES: To evaluate the efficacy and safety of a thermal mode
Erbium:YAG laser several in-vivo morphological as well as clinical changes were
monitored in a multi-center investigation. STUDY DESIGN/MATERIALS AND METHODS: An
Erbium:YAG laser was used at a thermal mode with sub-ablative fluences of 2.1 and
3.1 J/cm(2) with parallel air cooling to treat either periorbital, perioral
rhytides or patients with post-traumatic or acne scars. Two treatments were
applied 2 months apart, with follow-up at 1, 3, 6, and 12 months post-treatment.
Photographs were taken before and at each follow-up visit and evaluated by three
blinded independent reviewers. Histology and immunohistochemistry for pro
collagen expression were investigated. Optical coherence tomography (OCT) was
performed before, and at 4, 14, and 28 days after single pass treatment with
Erbium:YAG thermal pulses. RESULTS: The improvement of rhytides at 1-3 months
follow-up was graded as excellent in 19%, good in 19%, fair in 31%, and no
improvement in 31%. At the 6- to 12-month follow-up, the improvement was
excellent in 40%, good in 40%, fair in 20%, and no improvement in 0%. The
improvement of scars at 3-6 months follow-up was graded as excellent in 50%, good
in 25%, fair in 25%, and no improvement in 0%. Intra- and post-operative
discomfort was described as mild by the patients. OCT, histological sections and
immunohistochemistry demonstrated production of new collagen bundles.
CONCLUSIONS: Thermal Erbium:YAG pulses can induce collagen neogenesis, as proved
by temperature elevation and morphological changes in the upper dermis. This
leads clinically to visible and long lasting reduction of wrinkles and scars
after applying multiple passes with minimal side-effects.
PMID- 17036286
TI - Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness.
AB - OBJECTIVE: The fukutin gene (FKTN) is the causative gene for Fukuyama-type
congenital muscular dystrophy, characterized by rather homogeneous clinical
features of severe muscle wasting and hypotonia from early infancy with mental
retardation. In contrast with the severe dystrophic involvement of skeletal
muscle, cardiac insufficiency is quite rare. Fukuyama-type congenital muscular
dystrophy is one of the disorders associated with glycosylation defects of alpha
dystroglycan, an indispensable molecule for intra-extra cell membrane linkage.
METHODS: Protein and functional analyses of alpha-dystroglycan and mutation
screening of FKTN and other associated genes were performed. RESULTS:
Surprisingly, we identified six patients in four families showing dilated
cardiomyopathy with no or minimal limb girdle muscle involvement and normal
intelligence, associated with a compound heterozygous FKTN mutation. One patient
died by rapid progressive dilated cardiomyopathy at 12 years old, and the other
patient received cardiac implantation at 18 years old. Skeletal muscles from the
patients showed minimal dystrophic features but have altered glycosylation of
alpha-dystroglycan and reduced laminin binding ability. One cardiac muscle that
underwent biopsy showed altered glycosylation of alpha-dystroglycan similar to
that observed in a Fukuyama-type congenital muscular dystrophy patient.
INTERPRETATION: FKTN mutations could cause much wider spectrum of clinical
features than previously perceived, including familial dilated cardiomyopathy and
mildest limb girdle muscular dystrophy.
PMID- 17036287
TI - CLN3P, the Batten's disease protein, is a novel palmitoyl-protein Delta-9
desaturase.
AB - OBJECTIVE: Batten's disease, one of the most common recessively inherited,
untreatable, neurodegenerative diseases of humans, is characterized by
progressive neuronal loss and intraneuronal proteolipid storage. Although the
gene for the disorder was cloned more than a decade ago, the function of the
encoded protein, CLN3P, has not been defined thus far. METHODS: Sequence analysis
using the Pfam server identified a low stringency match to a fatty acid
desaturase domain in the N-terminal sequence of CLN3P. We developed a fatty acid
desaturase assay based on measurement of desaturase products by gas
chromatography/mass spectrometry. RESULTS: We show that CLN3P is a novel
palmitoyl-protein Delta-9 desaturase, which converts membrane-associated
palmitoylated proteins to their respective palmitoleated derivatives. We have
further demonstrated that this palmitoyl-protein Delta-9 desaturase activity is
deficient in cln3(-/-) mouse pancreas and is completely ablated in neuroblastoma
cells by RNA inhibition. INTERPRETATION: We propose that palmitoyl-protein
desaturation defines a new mechanism of proteolipid modification, and that
deficiency of this process leads to the signs and symptoms of Batten's disease.
PMID- 17036288
TI - Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C
NMR of urinary menthol glucuronide.
AB - Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject
following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose.
Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high
signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin
coupled multiplet components within each (13)C resonance by (13)C NMR. The [U
(13)C]glucuronide isotopomer derived via direct pathway conversion of [U
(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and
[1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway
metabolism of [U-(13)C]glucose. In a second study, a group of four overnight
fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint
oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min
constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment
of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C
isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6%
+/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide
enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic
UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP),
and the Cori cycle accounted for at least 32% +/- 10% of GP.
PMID- 17036289
TI - Parallel RF transmission with eight channels at 3 Tesla.
AB - Spatially selective RF waveforms were designed and demonstrated for parallel
excitation with a dedicated eight-coil transmit array on a modified 3T human MRI
scanner. Measured excitation profiles of individual coils in the array were used
in a low-flip-angle pulse design to achieve desired spatial target profiles with
two- (2D) and three-dimensional (3D) k-space excitation with simultaneous
transmission of RF on eight channels. The 2D pulse excited a high-resolution
spatial pattern in-plane, while the 3D trajectory produced high-quality slice
selection with a uniform in-plane excitation despite the highly nonuniform
individual spatial profiles of the coil array. The multichannel parallel RF
excitation was used to accelerate the 2D excitation by factors of 2-8, and
experimental results were in excellent agreement with simulations based on the
measured coil maps. Parallel RF transmission may become critical for robust and
routine human studies at very high field strengths where B(1) inhomogeneity is
commonly severe.
PMID- 17036291
TI - Electrochemical switching of the cubic nonlinear optical properties of an
aryldiethynyl-linked heterobimetallic complex between three distinct states.
PMID- 17036290
TI - Fluorescence visualization of newly synthesized proteins in mammalian cells.
PMID- 17036292
TI - A virus spotlighted by an autonomous DNA machine.
PMID- 17036293
TI - Total synthesis of paliurine F.
PMID- 17036294
TI - Dynamically self-assembling metalloenzyme models based on calixarenes.
PMID- 17036296
TI - Chemisorption-induced double hydrogen bonding, self-assembly, and
stereoselection.
PMID- 17036295
TI - Substrate mimicry in an activity-based probe that targets the nitrilase family of
enzymes.
PMID- 17036297
TI - Formation and stability of G-quadruplexes self-assembled from guanine-rich
strands.
AB - Electrospray ionization mass spectrometry (ESI-MS) was utilized to investigate
the formation and stability of G-quadruplexes. For the 15 6-nt oligonucleotides
tested, ESI-MS indicated that formation of a parallel tetramer quadruplex
requires at least four continuous guanines in the 6-nt sequence. In addition, the
G-rich strands prefer to employ "self-association" in the formation of the G
quadruplex rather than hybridized integration, and the thermodynamic-stability
order of these three G-quadruplexes is Q(2)>Q(1)>Q(3).
PMID- 17036298
TI - Synthesis and characteristics of a nonaggregating
tris(tetrathiafulvaleno)dodecadehydro[18]annulene.
AB - A new tris(tetrathiafulvaleno)dodecadehydro[18]annulene with six peripheral n
hexyl substituents was prepared by oxidative Glaser-Hay cyclization of a
corresponding diethynylated tetrathiafulvalene (TTF) precursor. The electronic
properties of the neutral and oxidized species were studied by both UV/Vis
absorption spectroscopy and electrochemistry. From these studies, it transpires
that the strongly violet-colored macrocycle does not aggregate in solution to any
significant degree, which was confirmed by (1)H NMR spectroscopy. This reluctance
towards aggregation contrasts that observed for related TTF-annulenes containing
other peripheral substitutents. Oxidation of the TTF-annulene occurs in two three
electron steps as inferred from both the peak amplitudes and the
spectroelectrochemical study. We find that the tris(TTF)-fused
dehydro[18]annulene is more difficult to oxidize (by +0.20 V) than the silyl
protected diethynylated mono-TTF precursor. In contrast, the first vertical
ionization energy calculated at the B3 LYP/6-311+G(2d,p) level for the parent
tris(TTF)-fused dehydro[18]annulene devoid of peripheral hexyl substituents is in
fact lower (by 0.44 eV). Moreover, the surface morphology of 1 d drop-cast on a
mica substrate was investigated by atomic force microscopy (AFM). Crystalline
domains with slightly different orientations were observed. The thickness of
individual layers seen in the crystalline domains and the thickness of a
monolayer obtained from a very dilute solution were determined to 1.8-1.9 nm.
This thickness corresponds to the diameter of the macrocycle and the layers seen
in the film are apparently formed when the molecules stack in the horizontal
direction relative to the substrate.
PMID- 17036299
TI - Room-temperature Au(I)-catalyzed C-C bond formation through a tandem Friedel
Crafts-type addition/carbocyclization reaction.
PMID- 17036300
TI - Real-time interactive MRI-guided cardiac surgery: aortic valve replacement using
a direct apical approach.
AB - Minimally invasive cardiac surgery requires arresting and emptying of the heart,
which compromises visualization of the surgical field. In this feasibility study
a novel surgical procedure is demonstrated in which real-time MRI is used to
guide the placement of a prosthetic aortic valve in the beating heart via direct
apical access in eight porcine hearts. A clinical stentless bioprosthetic valve
affixed to a platinum stent was compressed onto a balloon-tipped catheter. This
was fed through a 15-18-mm delivery port inserted into the left ventricular (LV)
apex via a minimally invasive subxyphoid incision. Using interactive real-time
MRI, the surgeon implanted the prosthetic valve in the correct location at the
aortic annulus within 90 s. In four of the animals immediately after
implantation, ventricular function, blood flow through the valve, and myocardial
perfusion were evaluated with MRI. MRI-guided beating-heart surgery may provide
patients with a less morbid and more durable solution to structural heart
disease.
PMID- 17036301
TI - Experimentally-derived functional form for a population-averaged high-temporal
resolution arterial input function for dynamic contrast-enhanced MRI.
AB - Rapid T(1)-weighted 3D spoiled gradient-echo (GRE) data sets were acquired in the
abdomen of 23 cancer patients during a total of 113 separate visits to allow
dynamic contrast-enhanced MRI (DCE-MRI) analysis of tumor microvasculature. The
arterial input function (AIF) was measured in each patient at each visit using an
automated AIF extraction method following a standardized bolus administration of
gadodiamide. The AIFs for each patient were combined to obtain a mean AIF that is
representative for any individual. The functional form of this general AIF may be
useful for studies in which AIF measurements are not possible. Improvements in
the reproducibility of DCE-MRI model parameters (K(trans), v(e), and v(p)) were
observed when this new, high-temporal-resolution population AIF was used,
indicating the potential for increased sensitivity to therapy-induced change.
PMID- 17036303
TI - Selective suppression of artifact-generating echoes in cine DENSE using through
plane dephasing.
AB - In displacement-encoded imaging with stimulated echoes (DENSE), tissue
displacement is encoded in the phase of the stimulated echo. However, three
echoes generally contribute to the acquired signal (the stimulated echo, the
complex conjugate of the stimulated echo, and an echo due to T(1) relaxation). It
is usually desirable to suppress all except the stimulated echo, since otherwise
the additional echoes will cause displacement measurement errors. Ideally,
suppression of the artifact-generating echoes would be independent of time, T(1),
and displacement-encoding frequency, and would not require additional
acquisitions. In this study through-plane gradients were used to selectively
dephase artifact-generating echoes without causing significant signal loss of the
stimulated echo. A cine DENSE sequence was modified to include dephasing
gradients and perform complementary spatial modulation of magnetization (CSPAMM).
For single-acquisition cine DENSE using dephasing alone, artifact suppression was
similar to CSPAMM with two acquisitions. The use of dephasing with CSPAMM
required two acquisitions, but demonstrated greater artifact suppression than
CSPAMM alone or dephasing alone.
PMID- 17036302
TI - Feasibility of in vivo identification of endogenous ferritin with positive
contrast MRI in rabbit carotid crush injury using GRASP.
AB - In vivo markers that allow for detection of ferritin within atheromatous plaque
may be useful for identifying iron-catalyzed hydroxyl-radical formation and
subsequent lipid peroxidation. Recently, a positive contrast MR technique-
GRadient echo Acquisition for Superparamagnetic particles/suscePtibility (GRASP)-
was used to identify the presence of magnetic entities in phantom models. The aim
of the current study was to determine the feasibility of using GRASP in
conjunction with conventional T(2) (*)-weighted (T(2) (*)W) gradient-echo (GRE)
sequences for identifying ferritin/hemosiderin deposition using in vitro and in
vivo models of thrombus. In vitro thrombi were prepared by incubating blood with
ferritin. MRI was performed using conventional GRE sequences and GRASP. The
results indicate that GRASP was able to verify ferritin deposition in in vitro
thrombi. In vivo thrombi were created using a crush injury model in rabbits. The
signal enhancement obtained using conventional GRE sequences and GRASP was
compared with the location of iron deposition by histology. In all of the animals
the GRASP signal correlated with signal loss by conventional GRE, and
ferritin/hemosiderin deposition by histology. GRASP sequences in combination with
conventional GRE sequences may be used to detect the presence of ferritin
deposition in in vitro thrombi and in vivo crush-injured rabbit carotid arteries.
PMID- 17036304
TI - Can MM-PBSA calculations predict the specificities of protein kinase inhibitors?
AB - An application of the molecular mechanics Poisson-Boltzmann surface area (MM
PBSA) protocol to the prediction of protein kinase inhibitor selectivity is
presented. Six different inhibitors are placed in equivalent orientations in each
of six different receptors. Fully solvated molecular dynamics is then run for 1
ns on each of the 36 complexes, and the resulting trajectories scored, using the
implicit solvent model. The results show some correlation with experimentally
determined specificities; anomalies may be attributed to a variety of causes,
including difficulties in quantifying induced fit penalties and variabilities in
normal modes calculations. Decomposing interaction energies on a per-residue
basis yields more useful insights into the natures of the binding modes and
suggests that the real value of such calculations lies in understanding
interactions rather than outright prediction.
PMID- 17036305
TI - Expression patterns of ubiquitin, heat shock protein 70, alpha-actin and beta
actin over the molt cycle in the abdominal muscle of marine shrimp Litopenaeus
vannamei.
AB - Crustacean muscle growth is discontinuous due to molt cycle. To characterize molt
related gene expression patterns, we studied the mRNA levels of molecular
chaperone-ubiquitin and heat shock protein 70 (Hsp 70) in comparison with muscle
protein alpha-actin and beta-actin in marine shrimp Litopenaeus vannamei. Total
RNA from abdominal muscle was isolated from 3-month-old animals in six different
molt stages. The mRNA levels of target genes were detected by reverse
transcriptase-multiplex PCR and expressed as the ratio to elongation factor
1alpha. Ubiquitin mRNA levels were relatively steady over all stages of the molt
cycle. Hsp70 levels were not detectable in early postmolt and late premolt
stages, but showed a progressive increase from late postmolt to intermolt stages.
Expression levels of alpha-actin gene were lower during postmolt, reached a
plateau in intermolt and remained relatively high in premolt stage. Levels of
beta-actin increased progressively from postmolt to intermolt, reaching a maximum
value in premolt. Therefore, the mRNAs encoding for ubiquitin and Hsp 70 in
abdominal muscle did not increase significantly in premolt stages, which is
typically associated with claw muscle degradation. Muscle structural alpha-actin
and cytoskeletal beta-actin were increased during intermolt and premolt stages,
suggesting high muscle growth during these stages in the abdominal muscle of the
L. vannamei.
PMID- 17036306
TI - Biosensor-based characterization of serum antibodies during development of an
anti-IgE immunotherapeutic against allergy and asthma.
AB - Antibody responses, induced in Cynomolgus monkey by recombinant IgE-derived
immunotherapeutic protein against atopic allergies and asthma, were characterized
using label-free, real-time protein interaction analysis. The effects of two
different immunotherapeutic proteins were compared. Active concentrations of
specific anti-IgE antibodies formed were determined in sera sampled at multiple
time points, using conditions of total mass transport limitation that were proved
to exist on the sensor surface. These concentrations varied from about 0.4 to 35
microg/ml among the monkeys and throughout the immunization period. Based on
these concentrations, the rate and affinity constants for the binding of antibody
populations to the antigen could be determined. The apparent equilibrium
dissociation constant decreased during the immunization period, for all the
monkeys, by a factor between 6 and 50, ending at values from approximately 2 x
10(-9) to approximately 2 x 10(-11) M among the animals. This affinity maturation
was attributable to the changes in both rate constants, although the magnitude of
the contribution of each constant depended partly on specimen, but primarily on
the immunotherapeutic used. The immunotherapeutic proteins examined showed
excellent immunogenic properties, providing the basis for a new and effective
treatment for allergy and asthma.
PMID- 17036307
TI - The muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet):
surveillance methodology.
AB - BACKGROUND: This report focuses on the common protocol developed by the Muscular
Dystrophy Surveillance Tracking and Research Network (MD STARnet) for population
based surveillance of Duchenne and Becker muscular dystrophy (DBMD) among 4
states (Arizona, Colorado, Iowa, and New York). METHODS: The network sites have
developed a case definition and surveillance protocol along with software
applications for medical record abstraction, clinical review, and pooled data.
Neuromuscular specialists at each site review the pooled data to determine if a
case meets the case criteria. Sources of potential cases of DBMD include
neuromuscular specialty clinics, service sites for children with special
healthcare needs, and hospital discharge databases. Each site also adheres to a
common information assurance protocol. RESULTS: A population-based surveillance
system for DBMD was created and implemented in participating states. CONCLUSIONS:
The development and implementation of the population-based system will allow for
the collection of information that is intended to provide a greater understanding
of DBMD prevalence and health outcomes.
PMID- 17036308
TI - Incorporating genetic analyses into birth defects cluster investigations:
strategies for identifying candidate genes.
AB - BACKGROUND: Incorporating genetic analyses into birth defect cluster
investigations may increase understanding of both genetic and environmental risk
factors for the defect. Current constraints of most birth defect cluster
investigations make candidate gene selection the most feasible approach. Here, we
describe strategies for choosing candidate genes for such investigations, which
will also be applicable to more general gene-environment studies. METHODS: We
reviewed publicly available web-based resources for selection of candidate genes
and identification of risk factors, as well as publications on different
strategies for candidate gene selection. RESULTS: Candidate gene selection
requires consideration of available gene-disease databases, previous
epidemiological studies, animal model research, linkage and expression studies,
and other resources. We describe general considerations for utilizing available
resources, as well as provide an example of a search for candidate genes related
to gastroschisis. CONCLUSIONS: Available web resources could facilitate selection
of candidate genes, but selection of optimal candidates will still require a
strong understanding of genetics and the pathogenesis of the defect, as well as
careful consideration of previous epidemiological studies.
PMID- 17036309
TI - Parietal bone agenesis with gracile bones and splenic hypoplasia/aplasia: clinico
pathologic report and differential diagnosis with review of cranio-gracile bone
syndromes, "osteocraniostenosis" and Kleeblattschadel.
AB - The findings in a newborn male with agenesis of parietal bones, gracile long
bones, and hypoplasia of the spleen are presented. Although parietal agenesis is
unique, the findings are compatible with 18 previously reported cases
characterized by cranial hypomineralization, Kleeblatschadel, gracile bones, and
splenic aplasia/hypoplasia, the nomenclature for which has been descriptive:
gracile bone disorders, "osteocraniostenosis," "osteocraniosplenic syndrome." The
term "osteocraniostenosis" may be inappropriate in that craniostenosis has been
infrequently reported, a feature also of importance with respect to the
pathogenesis of the Kleeblatschadel. The group likely reflects heterogeneous
etiology and pathogenesis. Precedent, however, including animal models, justifies
consideration of genetic aberrations, in particular, mutations in homeobox genes.
(c) 2006 Wiley-Liss, Inc.
PMID- 17036310
TI - Association between the NAT1 1095C > A polymorphism and homocysteine
concentration.
PMID- 17036311
TI - Atypical cases of Angelman syndrome.
AB - Angelman syndrome (AS) is a profound disorder notable for mental retardation and
severe language deficits that results from lack of function of the maternally
inherited copy of the UBE3A gene. Chromosome deletions of 15q11q13, paternal
uniparental disomy (UPD), UBE3A gene mutations, and imprinting center defects are
all commonly recognized mechanisms that disrupt the function of the maternal copy
of the UBE3A gene. We report here two patients with different atypical etiologies
of AS. The first patient is a 3-year-old boy with global developmental delay,
severe speech deficits, seizures, and very happy disposition. Southern blot
analysis for the maternal and paternal chromosome 15 methylation products showed
a mosaic methylation pattern, suggesting an imprinting center defect. The second
patient is a 4(1/2)-year-old boy with global developmental delay, no expressive
language, microcephaly, seizures, and ataxic gait. Array-based comparative
genomic hybridization (CGH) demonstrated a loss in copy number for two
overlapping clones encompassing the UBE3A gene, indicating a partial deletion
within UBE3A. His mother, who was adopted, had an identical pattern, suggesting
that her deletion was probably on her paternally imprinted allele. These patients
illustrate the expanding spectrum of molecular findings in AS, reinforce the need
to maintain suspicion when clinical features suggest AS but initial testing is
normal, and show the power of CGH as a tool to uncover partial UBE3A deletions.
PMID- 17036312
TI - Attitudes of genetic counselors towards expanding newborn screening and offering
predictive genetic testing to children.
AB - There is movement to expand newborn screening (NBS) to include conditions that
challenge the traditional public health screening criteria. Little is known about
the attitudes of genetic counselors towards expanding NBS and offering predictive
genetic tests to children. For our study genetic counselors completed an internet
survey posted on the National Society of Genetic Counselors Listserv regarding
five conditions: cystic fibrosis (CF), Duchenne muscular dystrophy (DMD), glucose
6-phosphate dehydrogenase deficiency (G6PD), fragile X (FraX), and type 1
diabetes (T1D). The survey addressed attitudes towards: (1) testing high-risk
infants; (2) mandatory NBS; (3) population screening beyond the newborn period;
and (4) testing one's own child. Two hundred sixty-seven usable surveys were
received. Over two-thirds of respondents supported testing high-risk infants for
all conditions except T1D (22%). CF was the only condition for which there was
majority support for both mandatory NBS (56%) and later population screening
(60%). For all other conditions, later population screening was preferred over
NBS (P or
=30 kg/m(2) to a BMI of 18-22.9 kg/m(2) [pooled multivariate (MV) RR, 1.16; 95%
CI: 0.89-1.52]. A weak, but statistically significant, association was observed
for the same comparison after excluding bladder cancer cases diagnosed within the
first 4 years of follow-up (pooled MV RR, 1.33; 95% CI: 1.01-1.76). Height was
not related to bladder cancer risk (pooled MV RR, 0.82; 95% CI: 0.65-1.03, top
vs. bottom quintile). Total recreational physical activity also was not
associated with the risk of bladder cancer (pooled MV RR, 0.97; 95% CI: 0.77
1.24, top vs. bottom quintile). Our findings do not support a role for BMI,
height or physical activity in bladder carcinogenesis.
PMID- 17036324
TI - Smoking and alcohol drinking in relation to risk of gastric cancer: a population
based, prospective cohort study.
AB - The relations between tobacco, alcohol and risk of gastric cancer need to be
established, and any gain from preventive measures should be estimated. We
conducted a population-based, prospective cohort study in Nord-Trondelag county
in Norway. During 1984-1986, adult residents were invited to a health survey and
they answered questionnaires that assessed exposure to tobacco and alcohol,
together with potential confounding factors. The exposure assessment regarding
alcohol was limited to a 14-day period. New gastric cancers that occurred during
follow-up (1984-2002) were identified by linkage to the Norwegian Cancer
Registry. Cox proportion hazards regression models were used to calculate hazard
ratios (HRs) with 95% confidence intervals (CI), adjusted for sex, education and
body mass index. Follow-up of 1,117,648 person-years at risk among 69,962 cohort
members revealed 251 gastric cancers, including 224 noncardia cancers. The risk
was almost twice as high in daily smokers (HR = 1.88 [CI 95% = 1.33-2.67]) as in
never smokers. Independent dose-response relations were found with earlier age at
initiation (p = 0.02), frequency (p = 0.00) and duration of smoking (p = 0.00).
Attributable risk (AR) of gastric cancer among current smokers was 8.7/100,000
person-years and the corresponding population AR was 18.4%. No statistically
significant associations between various degrees of exposure to alcohol and risk
of gastric cancer was revealed, but combined high use of cigarettes (>20/day) and
alcohol (>5 occasions/14 days) increased the risk of noncardia gastric cancer
nearly 5-fold (HR = 4.90 [95% CI = 1.90-12.62]), compared to nonusers. It is
concluded that smoking is a dose-dependent risk factor for gastric cancer.
Combined high exposure to smoking and alcohol further increases the risk.
Successful preventive measures could considerably reduce the incidence of gastric
cancer.
PMID- 17036325
TI - The changing incidence and sites of colorectal cancer in the Israeli Arab
population and their clinical implications.
AB - Israeli Arabs have been at low risk for colorectal cancer (CRC) and had mainly
proximal cancer, but increasing CRC is now noted. We examined this trend and CRC
site and compared them to the total Jewish population and to the low-risk Jews of
Asian-African origin. Israel Cancer Registry CRC data, 1982-2002, for Arabs and
Jews was computed by gender, age and site: rectal cancer included recto-sigmoid
junction; "right-sided" CRC included the proximal colon up to and also the
splenic flexure. During 1982-2002, Arab CRC trends increased significantly in
both sexes due to left-sided CRC (women, p = 0.01; men, p = 0.02) and rectal
cancers (p = 0.05). Left-sided CRC increased significantly in both men and women
aged > or = 65 years (p = 0.02). Comparing 1982-1984 to 2000-2002, the proportion
of right-sided CRC decreased in both genders (p < 0.01) from 39.4 to 27.1% of
male CRC, and from 44.8 to 31.3% in females. In general, this pattern of
increasing rectal and left-sided CRC had been seen over a decade earlier in Jews
of Asian-African origin and then their trend reversed during the last decade. In
conclusion, there is a recent trend for left-sided CRC in Israeli Arabs, probably
related to their changing life style. These results should influence their cancer
preventive lifestyle recommendations, and CRC screening and diagnostic
methodologies used.
PMID- 17036326
TI - Bulky DNA adducts as risk indicators of lung cancer in a Danish case-cohort
study.
PMID- 17036327
TI - Exploring the joint effects of silicosis and smoking on lung cancer risks.
AB - Cigarette smoking and silicosis are potential causes of lung cancer among workers
exposed to silica dust, but their joint effects are unclear. We explored the
possible interactions between silicosis and smoking on lung cancer risks by
summarizing data from the published literature. The standardized mortality ratio
or standardized incidence ratio reported in each published report was first
adjusted using "smoking adjustment factors" to correct for the biased estimation
of the expected numbers of lung cancer among smokers and nonsmokers when using
general population rates in the indirect standardization process. The ratio of
the effect of silicosis on lung cancer risk among smokers to that among nonsmoker
was calculated and named the "relative silicosis effect (RSE)". The synergy index
was estimated to assess the additive interaction. Metaanalyses were used to
obtain the weighed means of the RSE and synergy index. Ten cohort studies were
reviewed and combined to yield a weighed RSE of 0.29 (95% CI: 0.20, 0.42),
indicating negative risk-ratio multiplication between smoking and silicosis on
the lung cancer risk. The combined weighed synergy index was 1.00 (95% CI: 0.79,
1.26), suggesting no departure from additivity. Sensitivity analyses showed that
both estimates were quite robust. The independent risk-ratio effect of silicosis
on lung cancer in smokers was about 30% of that in nonsmokers, and the joint
effects of smoking and silicosis on the risk of lung cancer did not deviate from
additivity and hence did not support biological synergism/antagonism.
PMID- 17036328
TI - Re: "Bulky DNA adducts as risk indicators of lung cancer in a Danish case-cohort
study".
PMID- 17036329
TI - Rapid fat suppression in MRI of the breast with short binomial pulses.
AB - PURPOSE: To develop a faster method of fat suppression for use in dynamic
contrast enhanced MRI of the breast. MATERIALS AND METHODS: A method of fast fat
suppression is presented using spatially nonselective rapid binomial pulses. In
contrast to conventional binomial frequency-selective pulses, these short pulses
are applied without interpulse delay, allowing for very rapid spectrally
selective excitation. RESULTS: Effective water excitation and fat suppression
were achieved in breast MRI at 3.0 Tesla with total excitation time as low as 160
microsec, which is several times shorter than the excitation time of currently
used fat suppression techniques. Rapid fat suppression comes at the expense of
increased specific absorption rate (SAR) and mildly degraded quality of
suppression. A flexible tradeoff of short imaging time vs. SAR can be made to
optimize imaging speed for fat-suppressed breast MRI. CONCLUSION: Rapid binomial
pulses can be used for dynamic contrast enhanced breast MRI with excitation times
significantly shorter than currently used fat suppression pulses. Shorter
excitation time allows more rapid imaging, allowing greater temporal and spatial
resolution for characterization of breast lesions.
PMID- 17036330
TI - Antitumor effects of a recombinant fowlpox virus expressing Apoptin in vivo and
in vitro.
AB - Apoptin is a chicken anemia virus-derived, p53-independent, bcl-2-insensitive
apoptotic protein with the ability to specifically induce apoptosis in tumor
cells. To explore the use of the Apoptin gene in cancer gene therapy, we
constructed a recombinant fowlpox virus expressing the Apoptin protein (vFV
Apoptin) and compared the tumor-killing activity of the recombinant virus with
that of wild-type fowlpox virus in the human hepatoma cell line HepG2. We found
that although cells were somewhat resistant to the basal cytotoxic effect of wild
type fowlpox virus, infection with vFV-Apoptin caused a pronounced, additional
cytotoxic effect. Furthermore, cell death and disruption of tumor integrity were
apparent in the vFV-Apoptin-infected cells. We also tested whether fowlpox virus
mediated expression of Apoptin in tumor cells could stimulate an antitumor effect
by injecting aggressive subcutaneous tumors derived from H22 mouse hepatoma cells
in C57BL/6 mice with vFV-Apoptin. We found that fowlpox virus-mediated
intratumoral expression of the Apoptin gene can induce protective and therapeutic
antitumor effects and significantly increase survival. Taken together, these data
indicate that infection of tumors with fowlpox virus expressing Apoptin inhibits
tumor growth, induces apoptosis and may be an effective cancer treatment.
PMID- 17036331
TI - Interactive effects of lifetime alcohol consumption and alcohol and aldehyde
dehydrogenase polymorphisms on esophageal cancer risks.
AB - In our previous study, we found that polymorphisms of alcohol and aldehyde
dehydrogenase (ADH1B and ALDH2) are important risks for esophageal squamous cell
carcinoma in a Taiwanese population. In this study, we increased the sample size
to investigate the modifying effect of lifetime alcohol consumption on the
association between ADH1B and ALDH2 genotypes and the risks of esophageal cancer.
A multicenter hospital-based case-control study was conducted between August 2000
and June 2004. Three hundred and thirty newly-diagnosed esophageal squamous cell
carcinoma patients and 592 controls were recruited from National Taiwan
University Hospital in Taipei and Kaohsiung Veterans General Hospital and
Kaohsiung Medical University Hospital in Kaohsiung, Taiwan. Controls were matched
to the case patients by gender and age within 4 years (case:control = 1:1-4).
Polymorphisms of ADH1B and ALDH2 were genotyped by the method of PCR-RFLP.
Individuals with ADH1B*1/*1 genotype had a 3.99-fold risk (95% CI = 2.13-7.48) of
developing esophageal cancer, compared with those with ADH1B*2/*2 genotype, after
adjusted for appropriate covariates. Individuals with ALDH2*1/*2 and ALDH2*2/*2
had 4.99-fold risk (95% CI = 3.11-7.99) and 4.24-fold risk (95% CI = 1.52-11.84),
respectively, of developing esophageal cancer, compared with those with
ALDH2*1/*1, after adjusted for appropriate covariates. We also found a modifying
effect of lifetime alcoholic consumption on the association between genotypes of
ADH1B and ALDH2 on esophageal cancer risk. These results suggest that ADH1B and
ALDH2 polymorphisms play a pivotal role on esophageal cancer and that the effect
of these polymorphisms was modified by the amount of alcohol consumed.
PMID- 17036332
TI - Unbalanced expression of licensing DNA replication factors occurs in a subset of
mantle cell lymphomas with genomic instability.
AB - DNA licensing is a crucial process for chromosome replication control.
Deregulation of the licensing factors Cdt1, Cdc6 and the licensing inhibitor
geminin has been associated with DNA replication defects and chromosomal
instability. We examined the expression of these factors, in mantle cell lymphoma
(MCL) and non-neoplastic lymphoid samples, and analysed the potential role of
their deregulation in genomic instability. Geminin, Cdt1 and Cdc6 were
coordinately expressed in non-neoplastic tissues and most MCL in relationship to
the proliferative activity of the cells. However, 6 (18%) tumours showed an
unbalanced "licensing signature" characterized by a higher expression of Cdt1 and
Cdc6 than the negative regulator geminin. Tumours with this unbalanced signature
and p53/p14(ARF) alterations had significantly higher number of chromosome
abnormalities than lymphomas with p53/p14(ARF) alterations but with a normal
licensing signature. No aberrations of Cdct1, Cdc6, and geminin genes were
detected in cases with unbalanced licensing. However, tumours with p53/ARF
inactivation and unbalanced licensing signature had significantly higher cyclin
D1 levels than tumours with normal licensing signature. These results suggest
that an unbalanced mRNA expression of licensing regulatory genes may play a role
in the pathogenesis of the chromosomal instability of a subset of MCL with
inactivation of the p53/p14(ARF) pathway.
PMID- 17036333
TI - SPAN-XB core promoter sequence is regulated in myeloma cells by specific CpG
dinucleotides associated with the MeCP2 protein.
AB - SPAN-Xb is a novel cancer-testis antigen in multiple myeloma. We recently
demonstrated that SPAN-Xb expression in myeloma cells is regulated through
promoter methylation and could be upregulated by IL-7 and GM-CSF. In this present
study, we set out to investigate the mechanism of SPAN-XB expression and the
promoter association with the methyl-CpG binding protein (MeCP2). Elucidation of
these interactions is likely shed light on potential therapeutic strategies to
upregulate antigen levels for SPAN-Xb-based tumor vaccines. Using a panel of
truncated promoter constructs, we localize the core sequence of SPAN-XB promoter
to the 73 bp at the 3' end of the promoter, a region within the full length
promoter that lacks CpG dinucleotides. Reporter gene expression assays showed
that the core promoter function is significantly modulated by the adjacent CpG
sequences. Chromatin immunoprecipitation assays revealed a specific association
of MeCP2 with the promoter, and MeCP2 binding strongly correlated with repression
of SPAN-XB gene. Reactivation of the SPAN-XB gene by 5-azacytidine treatment
resulted in the loss of MeCP2 from this site. We, therefore, conclude that SPAN
XB core promoter function in myeloma cells is associated with MeCP2 protein
binding and regulated by specific CpG dinucleotide sequences.
PMID- 17036334
TI - Trigonocephaly in Muenke syndrome.
AB - Saethre-Chotzen syndrome is caused by mutations in the TWIST gene on chromosome
7p21.2. However, Muenke et al. [(1997); Am J Hum Genet 91: 555-564] described a
new subgroup carrying the Pro250Arg mutation in the fibroblast growth factor
receptor (FGFR) 3 gene on chromosome 4p16. Uni or bicoronal synostosis appears to
be the main clinical finding in both syndromes. We observed trigonocephaly as a
new manifestation in Muenke syndrome. As a consequence we advise to routinely
perform mutation analysis of the FGFR1, 2, and 3 genes in children with non
syndromic trigonocephaly.
PMID- 17036335
TI - CRELD1 mutations contribute to the occurrence of cardiac atrioventricular septal
defects in Down syndrome.
PMID- 17036336
TI - Whole genome microarray analysis of gene expression in an imprinting center
deletion mouse model of Prader-Willi syndrome.
AB - Prader-Willi syndrome (PWS) is caused by loss of paternally expressed genes in
the 15q11-q13 region. To further characterize alterations in gene expression in
this classical obesity syndrome we used whole genome microarrays to study a PWS
mouse model resulting from a paternally derived imprinting center (IC) deletion
(PWS IC deletion). These mice die generally within 2-3 days of life (reflective
of failure to thrive in infants with PWS) and therefore, the analysis was
performed on RNA extracted from the whole brain of PWS IC deletion mice and
normal littermates at less than 24 hr after birth. Of more than 45,000 probes
examined, 26,471 (59%) were detected for further analysis, and 69 had a
significant change in expression of at least 1.5-fold and a false discovery rate
(FDR) of 5%. Eight of the genes with differential expression were imprinted and
from the PWS critical region (PWSCR). The three genes with the highest expression
in the PWS IC mice were pro-opiomelanocortin (Pomc) and two transcripts of
unknown function. Pomc knockout mice have been shown to develop obesity.
Therefore, elevated Pomc RNA in PWS IC deletion neonatal mice may be an important
genetic factor in the survival of these mice as it may affect eating behavior.
Interestingly, Mc5r, a melanocortin receptor known to directly respond to Pomc
expression changes, was upregulated as well. Mc5r is known to be involved with
thermoregulation which is reportedly abnormal in PWS infants. These observations
support a role for Pomc and the network of genes involved in regulating energy
homeostasis in the early clinical findings of failure to thrive observed in PWS.
Other notable patterns include three previously unstudied transcripts that are
expressed only from the paternal allele under regulatory control of the IC and
include AK013560, BB3144814, and BB182944 (whose genes are located in the mouse
PWSCR on chromosome 7B). As expected, all the known paternally expressed genes
from the PWSCR had detection signals below the threshold in the PWS IC deletion
mice but were clearly detectable in control littermates. Several of the genes in
this study were further examined by quantitative reverse transcription-PCR (RT
PCR) to confirm their expression status. Further analysis of gene expression in
these mice may lead to novel pathways affected in PWS. These results, along with
other recent reports, suggest that the cumulative effect of modest changes in
expression of many genes, especially genes involved in energy metabolism,
contribute to the failure to thrive of infants with PWS.
PMID- 17036337
TI - Risks of human limb deficiency anomalies associated with 29 SNPs of genes
involved in homocysteine metabolism, coagulation, cell-cell interactions,
inflammatory response, and blood pressure regulation.
AB - This study explored risks of limb deficiency anomalies associated with 29 single
nucleotide polymorphisms (SNPs) of genes involved in homocysteine metabolism,
coagulation, cell-cell interaction, inflammatory response, and blood pressure
regulation. The authors genotyped 96 cases and 437 non-malformed controls from a
California population-based case-control study (1987-1988 birth cohort).
Increased risk of limb anomaly was observed for three SNPs: heterozygosity for F5
Arg506Gln, with an odds ratio (OR) of 2.5 (95% confidence interval (CI), 1.0,
6.5); heterozygosity for TNF (-376)G > A, OR 2.1 (0.7, 6.2); and homozygosity for
NPPA 2238T > C, OR 4.0 (1.1, 15.4). We hypothesized that effects of variant
genotypes in the presence of maternal smoking, and/or in the absence of
supplement intake, may exceed effects of any of these factors alone. In
particular, findings for polymorphisms in SERPINE1, ITGA2, SELE, TNF, LTA, NPPA,
GNB3, and ADRB2 supported the hypotheses, both for smoking and for supplement
intake. These results suggest involvement of genetic variation of biologically
relevant candidate genes, and gene-environment interaction, for some limb
anomalies whose pathogenesis may be related to altered vascular tone or
integrity.
PMID- 17036338
TI - X-chromosome inactivation patterns in females with Prader-Willi syndrome.
AB - Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by
loss of paternally expressed genes from the 15q11-q13 region generally due to a
paternally-derived deletion of the 15q11-q13 region or maternal disomy 15 (UPD).
Maternal disomy 15 is usually caused by maternal meiosis I non-disjunction
associated with advanced maternal age and after fertilization with a normal sperm
leading to trisomy 15, a lethal condition unless trisomy rescue occurs with loss
of the paternal chromosome 15. To further characterize the pathogenesis of
maternal disomy 15 process in PWS, the status of X-chromosome inactivation was
calculated to determine whether non-random skewing of X-inactivation is present
indicating a small pool of early embryonic cells. We studied X-chromosome
inactivation in 25 females with PWS-UPD, 35 with PWS-deletion, and 50 controls
(with similar means, medians, and age ranges) using the polymorphic androgen
receptor (AR) gene assay. A significant positive correlation (r = 0.5, P = 0.01)
was seen between X-chromosome inactivation and age for only the UPD group.
Furthermore, a significantly increased level (P = 0.02) of extreme X-inactivation
skewness (>90%) was detected in our PWS-UPD group (24%) compared to controls
(4%). This observation could indicate that trisomy 15 occurred at conceptus with
trisomy rescue in early pregnancy leading to extreme skewness in several PWS-UPD
subjects. Extreme X-inactivation skewness may also lead to additional risks for X
linked recessive disorders in PWS females with UPD and extreme X-chromosome
skewness.
PMID- 17036339
TI - In vivo measurement of plaque burden in a mouse model of Alzheimer's disease.
AB - PURPOSE: To demonstrate an MRI method for directly visualizing amyloid-beta
(Abeta) plaques in the APP/PS1 transgenic (tg) mouse brain in vivo, and show that
T1rho relaxation rate increases progressively with Alzheimer's disease (AD)
related pathology in the tg mouse brain. MATERIALS AND METHODS: We obtained in
vivo MR images of a mouse model of AD (APP/PS1) that overexpresses human amyloid
precursor protein, and measured T1rho via quantitative relaxometric maps.
RESULTS: A significant decrease in T1rho was observed in the cortex and
hippocampus of 12- and 18-month-old animals compared to their age-matched
controls. There was also a correlation between changes in T1rho and the age of
the animals. CONCLUSION: T1rho relaxometry may be a sensitive method for
noninvasively determining AD-related pathology in APP/PS1 mice.
PMID- 17036340
TI - Role of MRI in screening women at high risk for breast cancer.
AB - Breast cancer is diagnosed in over one million women worldwide every year. Until
breast cancer can be prevented, early detection offers the best chance for cure.
Mammographic screening is an effective method for early detection in average-risk
women. However, the sensitivity of mammography is decreased in women at high risk
for breast cancer. Because of its high sensitivity, multiple investigators have
studied the potential role of MRI in screening women at high risk. In the past
few years, results from eight major clinical trials exploring breast MRI as a
screening tool have been published. Combined, the studies included 4271 patients
and found 144 breast cancers detected by MRI, for an overall cancer yield of 3%.
The sensitivity of MRI ranged from 71% to 100% across the studies. Although its
reported specificity was variable, the call-back rates and risk of benign
biopsies were within acceptable limits. In general, patients who underwent breast
MRI screening had a 10% risk of being called back, and a 5% risk of having a
benign biopsy. This work reviews the literature and current practices and
recommendations for MRI as a screening tool for high-risk women.
PMID- 17036342
TI - Myocardial perfusion.
AB - Noninvasive cardiac magnetic resonance (CMR) imaging has progressed rapidly over
the past few years and will most likely become an integral part of the diagnostic
workup of patients with known or suspected coronary artery disease (CAD). In this
article the rationale for using perfusion-CMR is discussed, followed by a summary
of current state-of-the-art perfusion-CMR techniques that addresses
pharmacological stress, monitoring, pulse sequences, and doses of contrast media
(CM) for first-pass studies. In the second part, unresolved aspects of perfusion
CMR, such as the lack of fully established and validated imaging protocols, are
discussed. The optimum pulse sequence parameters, required cardiac coverage,
analysis algorithms, criteria for data quality, and other aspects remain to be
defined. Furthermore, since expertise in perfusion-CMR is not yet widely
available, training of physicians and technicians to perform perfusion-CMR
according to recognized standards is an important future requirement. In the last
part of the review, some ideas are proposed to improve the management of patients
with known or suspected CAD. This involves making a shift from a "reactive"
strategy, in which patients are typically approached when they are symptomatic,
to an "active" strategy, in which perfusion-CMR is performed for early detection
of high-risk patients so that revascularizations can be performed before
potentially deadly infarcts occur. An ideal test for such an active strategy
would be highly accurate, reliable, safe (and thus repeatable), and affordable.
Large multicenter trials have shown that in experienced centers perfusion-CMR is
reliable and repeatable, and it is hoped that future studies will demonstrate its
cost-effectiveness as well.
PMID- 17036341
TI - Analysis of a Scottish founder effect narrows the TAPVR-1 gene interval to
chromosome 4q12.
PMID- 17036343
TI - Polymicrogyria and deletion 22q11.2 syndrome: window to the etiology of a common
cortical malformation.
AB - Several brain malformations have been described in rare patients with the
deletion 22q11.2 syndrome (DEL22q11) including agenesis of the corpus callosum,
pachygyria or polymicrogyria (PMG), cerebellar anomalies and meningomyelocele,
with PMG reported most frequently. In view of our interest in the causes of PMG,
we reviewed clinical data including brain-imaging studies on 21 patients with PMG
associated with deletion 22q11.2 and another 11 from the literature. We found
that the cortical malformation consists of perisylvian PMG of variable severity
and frequent asymmetry with a striking predisposition for the right hemisphere (P
= 0.008). This and other observations suggest that the PMG may be a sequela of
abnormal embryonic vascular development rather than a primary brain malformation.
We also noted mild cerebellar hypoplasia or mega-cisterna magna in 8 of 24
patients. Although this was not the focus of the present study, mild cerebellar
anomalies are probably the most common brain malformation associated with
DEL22q11.
PMID- 17036344
TI - A case surviving for over a year of renal tubular dysgenesis with compound
heterozygous angiotensinogen gene mutations.
AB - Renal tubular dysgenesis (RTD) is a developmental abnormality of the renal
proximal tubules found in patients with Potter syndrome. We report a female
newborn with RTD who has survived for more than 18 months. Infusions of fresh
frozen plasma (FFP) in the early neonatal period were effective in raising and
maintaining her blood pressure. Peritoneal dialysis was required until the
appearance of spontaneous urination at 29 days after birth. Histopathological
examinations of the kidney revealed dilated renal tubular lumina and foamy
columnar epithelial cells in the renal tubules. Endocrinological studies showed a
discrepancy between low plasma renin activity (<0.1 ng/ml/hr) and high active
renin concentration (135,000 pg/ml), suggesting an aberration in the renin
substrate, angiotensinogen. Direct sequencing analysis revealed two novel
mutations in the coding region of the angiotensinogen gene (AGT): a nonsense
mutation in exon 2 (c.604C > T) and a frameshift deletion at nucleotide 1290 in
exon 5 (c.1290delT). The mutations were in the compound heterozygous state,
because each parent had each mutation. These findings suggest that
angiotensinogen deficiency is one of the causes of RTD. A treatment of the
condition with FFP may help to promote long survival.
PMID- 17036345
TI - Associated malformations in congenital diaphragmatic hernia cases in the last 15
years in a tertiary referral institute.
AB - This is a review of cases of perinatally diagnosed congenital diaphragmatic
hernia (CDH) with associated malformations with regard to time of diagnosis, side
of hernia, associated malformations, and outcome. The authors analyzed the data
of CDH cases with associated malformations from records of the I. Department of
Obstetrics and Gynecology, Semmelweis University Faculty of Medicine, Budapest,
between July 1, 1990 and June 30, 2005. The observed period was analyzed in two
parts. The pre- and postnatal examinations verified CDH in 100 cases, 71% of
which were associated with other malformations. In 52% (37/71) CDH was diagnosed
before the 24th week of gestation. The rate of early diagnosed cases doubled in
the second period. Ten percent (7/71) of cases were verified postnatally. Between
1990 and 1997, the percentage of right-sided hernia was 6% (2/34) while in the
second period it was 19% (7/37). The association with cardiovascular, chest, and
craniofacial anomalies doubled in the second period, while association of central
nervous system anomalies halved. Chromosome anomalies were verified in four
cases. Pregnancy was terminated in 53% (34/64) and 13% (4/30) of newborn infants
survived the perinatal period. Intrauterine or intrapartum death occurred in 8%
(5/64) of cases. The prevalence of cardiovascular, pulmonary, and craniofacial
anomalies doubled, while that of central nervous system malformations decreased.
The prevalence of other associated malformations has not changed significantly
between the two periods. The improvement of technical facilities and accumulated
experience make it possible to identify a higher number of associated
malformations before the 24th week of gestation.
PMID- 17036346
TI - Primary breast cancer phenotypes associated with propensity for central nervous
system metastases.
PMID- 17036347
TI - Visual function of police officers who have undergone refractive surgery.
AB - INTRODUCTION: The visual acuity and contrast sensitivity of police recruits and
officers was evaluated in both normal and dim illumination conditions to
determine whether officers who have had refractive surgery have compromised night
vision. METHODS: The control group consisted of 76 officers and recruits who have
not had refractive surgery and the refractive surgery group consisted of 22
officers and recruits who had refractive surgery. Visual acuity and contrast
sensitivity were measured under both room illumination and dim illumination. The
room illumination test series included high contrast acuity, low contrast acuity
and Pelli-Robson contrast sensitivity. The dim illumination test series included
high contrast acuity, low contrast acuity, Pelli-Robson contrast sensitivity,
license plate number acuity (with and without glare) and the Mesotest. RESULTS:
The general findings were that the refractive surgery group had lower acuity
scores on low contrast targets in both room and dim light levels along with a
reduction in the Mesotest scores with a glare source compared to the control
group. CONCLUSIONS: Although refractive surgery police recruits and officers had
reduced performance on some vision tests, these reductions were small and it is
unlikely that their performance on vision related tasks would be compromised, on
average. The major concern is the small number of refractive surgery candidates
whose results were well outside the range of the non-surgical candidates. Their
vision may be unacceptable for policing.
PMID- 17036348
TI - Industrial Pseudomonas folliculitis.
AB - INTRODUCTION: Complaints of poor water quality and skin rashes among workers at a
US cardboard manufacturing facility were investigated to determine potential
causes. METHODS: Employees were interviewed regarding work duties and health
symptoms. Areas of dermatitis in affected employees were visually examined.
Collected water samples were tested for potential chemical and microbial
contaminants. RESULTS: A total of 27 employees were identified with complaints of
recent skin rashes affecting primarily the upper and lower extremities.
Dermatitis complaints were associated with water contact and work in areas with
poor water quality. Water testing showed high levels of Pseudomonas aeruginosa.
Other tested substances were not at levels of concern. CONCLUSIONS: Overgrowth of
P. aeruginosa occurred in the water system shortly after the facility switched to
a closed-loop water recycling system and was the most likely cause of the
observed dermatitis. To our knowledge, this is the first reported outbreak of
Pseudomonas folliculitis in an industrial setting.
PMID- 17036349
TI - North American Guidelines for Children's Agricultural Tasks: five-year assessment
and priorities for the future.
AB - BACKGROUND: The North American Guidelines for Children's Agricultural Tasks
(NAGCAT) are a safety resource created to assist parents in selecting safe work
for their children 7-16 years of age. Since their release in 1999, a growing body
of scientific evidence has accumulated regarding NAGCAT. The purpose of this
project was to assess the current scientific and programmatic evidence regarding
the efficacy and utilization of the NAGCAT resource in order to determine the
priorities for the next 5 years. METHODS: A systematic, evidenced-based method
was employed to accomplish the project objectives. Our data sources included
results from a survey of agricultural safety practitioners and researchers, a
comprehensive synthesis of the peer-reviewed literature, and recommendations from
a priority-setting meeting. RESULTS: Five main priorities were identified: to
address the perceptions and barriers associated with the use and non-use of the
NAGCAT resource; to revise and re-format a core set of the guidelines; to develop
a NAGCAT resource dissemination/marketing plan; to provide training and support
for agricultural safety professionals and parents using NAGCAT; and to conduct
further research to facilitate accomplishing these priorities. CONCLUSIONS: This
assessment and priority identification process was successful in outlining the
next steps for the NAGCAT resource. As we move toward 2010, those involved in
pediatric agricultural injury prevention will have a blueprint to ensure that
NAGCAT are an effective and widely used resource for preventing work-related
injuries.
PMID- 17036350
TI - Long hours of work in the U.S.: associations with demographic and organizational
characteristics, psychosocial working conditions, and health.
AB - BACKGROUND: There are relatively few studies of large national databases that
contain information on working hours and health. The current study involved an
analysis of data from a quality of work life (QWL) module developed for the 2002
General Social Survey. This module collected work and health data from a
representative sample of the U.S. population (N=1,744). METHODS: Descriptive
analyses were conducted for five groups based on total hours worked per week:
part-time (1-34 hr/week), full-time (35-40 hr/week), lower overtime (41-48
hr/week), medium overtime (49-69 hr/week), and higher overtime (70+ hr/week).
Multiple logistic regression examined the association between these five
categories and several measures of health and well-being. RESULTS: Compared to
full-time workers, the three groups of overtime workers were more likely to be
male, white, and middle-aged, with higher levels of education and income. They
were also more likely to be self-employed, salaried, work as independent
contractors, have more than one job, and work split/irregular/on-call shifts.
Although overtime work was characterized by higher levels of job stress and
perceptions of overwork, it was also associated with increased levels of
participation in decision making and opportunities to develop special abilities.
Several significant associations emerged between hours of work and measures of
health and well-being, particularly for respondents in the higher overtime group
(70+ hr/week). CONCLUSION: Overtime workers differ from their part-time and full
time counterparts in several important areas. Some of these differences tended to
increase with the number of overtime hours worked, suggesting a linear
relationship. However, caution is warranted before generalizing the results of
this study to specific occupations or workplaces.
PMID- 17036351
TI - Workers' compensation experience of Colorado agriculture workers, 2000-2004.
AB - BACKGROUND: Agriculture is among the most hazardous of occupations. The lack of
information regarding agriculture injuries or fatalities has been recognized as
an obstacle for effective injury prevention. Workers' compensation claims data
for non-fatal injuries among agriculture and agri-business workers in the State
of Colorado between the years of 2000 and 2004. METHODS: Workers' compensation
claims are utilized to estimate injury claim incidence rates, determine the
distributions of sources, causes, types and body locations of injuries, and
estimate the costs of these injuries. RESULTS: Colorado agriculture and agri
business workers (e.g., cattle dealers, cattle or livestock raisers, dairy
farmers) have high rates of injury claims, especially in sectors that involve
interaction with animals or livestock. Grain milling operations had a high rate
of injury claims among agri-business operations. Injuries related to animals,
strains, machinery, and falls or slips were the most frequent among all
occupations analyzed. CONCLUSIONS: Understanding the occurrence of injuries among
Colorado agriculture and agri-business workers is critical to implementing and
evaluating effective intervention programs for specific agriculture-related
occupations. The development of safety interventions that address the worker
animal interface, fall protection systems, machinery usage, and overexertion
prevention strategies is recommended.
PMID- 17036352
TI - Psychopathology in the Lujan-Fryns syndrome: report of two patients and review.
AB - We report on two new patients, the propositus and his maternal uncle, with Lujan
Fryns syndrome (LFS). One presented with mild mental retardation and both patient
had Marfanoid habitus and similar craniofacial anomalies (they had a long and
narrow face, small mandible, high-arched palate, and hypernasal voice) as
previously reported by Lujan et al. in 1984 and Fryns and Buttiens in 1987. One
of our patients had agenesis of the corpus callosum as described by Lujan. The
second patient had an ascending aortic aneurysm like the patient described by
Wittine et al. 1999. Both patients showed similar behavior and psychiatric
disorders. In addition, we reviewed the literature for the presence of
psychopathology in LFS. After studying the 32 published cases and the 2 described
in this article, we found that more than 90% of the patients present with some
type of psychopathology, the most frequent being an autistic-like disorder. In
our opinion, the agenesis of the corpus callosum (complete or partial) and
ascending aorta aneurysm are manifestations of LFS, and thus brain MRI and
echocardiogram should be part of the routine evaluation. Additionally, the high
prevalence of psychopathological alterations in these patients suggests the need
for psychiatric evaluation at the time of diagnosis.
PMID- 17036354
TI - Complications of combined modality treatment of primary lower extremity soft
tissue sarcomas.
AB - BACKGROUND: Correlations between various patient, tumor, and treatment
characteristics and complications in patients undergoing combined modality
treatment for primary lower extremity soft-tissue sarcomas were investigated.
METHODS: Using the M. D. Anderson Radiation Oncology database, the records of the
subset of patients treated with combined radiation and limb-sparing surgery for
primary lower extremity soft-tissue sarcomas were retrospectively reviewed from
the years 1960 to 2003. RESULTS: In all, 412 patients were identified. With a
median follow-up of 9.3 years, there were a total of 113 (27%) acute wound
complications and 41 (13% at 20 years) chronic radiation-related limb
complications. Preoperative radiation and tumor sizes >5 cm were associated with
an increased risk of acute wound complications (34% preoperative vs. 16%
postoperative, P < .001; and 31% >5 cm vs. 17% < or =5 cm, P = .005). At 20 years
the radiation-related complication rate was higher in patients with a groin or
thigh tumor location (16% vs. 4% other; P = .008), prior acute wound
complications (20% vs. 10% no surgical complication), and a radiation dose > or
=60 grays (Gy) (18% vs. 9% for dose < 60 Gy; P = .04). Five fractures occurred,
resulting in a crude overall fracture rate of 1.2%. CONCLUSIONS: Patients treated
with preoperative radiation for larger tumors are more likely to have acute
surgical wound complications. Acute wound complications followed by postoperative
radiation are associated with chronic radiation-related limb problems, as are
higher radiation dose and proximal tumor location. The fracture rate is so low
that prophylactic fixation is not warranted.
PMID- 17036355
TI - Phase I clinical trial of bortezomib in combination with gemcitabine in patients
with advanced solid tumors.
AB - BACKGROUND: Bortezomib is the first proteasome inhibitor to show preliminary
evidence of activity against solid tumors. Findings from preclinical studies
prompted a Phase I trial to determine the maximum tolerated dose (MTD) and dose
limiting toxicities (DLTs) of bortezomib in combination with gemcitabine in
patients with recurring/refractory advanced solid tumors. The effect of
gemcitabine on proteasome inhibition by bortezomib in whole blood was also
investigated. METHODS: Bortezomib was administered as an intravenous bolus
injection on Days 1, 4, 8, and 11, with gemcitabine (30-minute infusion) on Days
1 and 8 of a 21-day cycle. Groups of > or =3 patients were evaluated at each dose
level. Escalating doses of gemcitabine 500 mg/m(2) to 1000 mg/m(2) with
bortezomib 1.0 mg/m(2) to 1.5 mg/m(2) were planned. RESULTS: There were no DLTs
in patients receiving bortezomib 1.0 mg/m(2) and gemcitabine 500 mg/m(2) to 1000
mg/m(2) in the first 3 dose levels. Dose-limiting nausea, vomiting,
gastrointestinal obstruction, and thrombocytopenia occurred in 4 of 5 evaluable
patients in dose level 4 (bortezomib 1.3 mg/m(2), gemcitabine 800 mg/m(2)),
establishing bortezomib 1.0 mg/m(2) and gemcitabine 1000 mg/m(2) as the MTD. Most
common Grade > or =3 toxicities were neutropenia (6 patients), thrombocytopenia
(5 patients), gastrointestinal disorders (6 patients), and general disorders (4
patients) such as fatigue. One patient with nonsmall cell lung carcinoma achieved
a partial response and 7 achieved stable disease. Inhibition of 20S proteasome
activity by bortezomib was unaffected by gemcitabine coadministration.
CONCLUSION: Dosages of bortezomib and gemcitabine suitable for further evaluation
of antitumor activity have been established.
PMID- 17036356
TI - Abstracts of the American Society of Cytopathology 54th Annual Scientific
Meeting, November 3-8, 2006, Toronto, Canada.
PMID- 17036357
TI - Long-term safety of cardiac magnetic resonance imaging performed in the first few
days after bare-metal stent implantation.
AB - PURPOSE: To investigate the long-term safety of cardiac magnetic resonance
imaging (CMR) performed one to seven days after coronary artery stent (bare
metal) implantation. MATERIALS AND METHODS: We analyzed 119 consecutive patients
with acute myocardial infarction (MI) who underwent emergency coronary stent
implantation with a bare-metal stent. CMR using a 1.5T scanner was performed on
51 patients (42.9%) at a mean of 2.7+/-3.1 days after stent implantation (CMR+
group), and the remaining 68 patients (57.1%) served as controls (CMR- group).
The patients were followed up to six months for major adverse cardiac events.
RESULTS: The average stent size was 3.3+/-0.5x18.4+/-6.7 mm, and 86% of the
stents were made of 316L stainless steel. There were no significant differences
between the CMR+ and CMR- groups in terms of infarct features, angiographic
findings, or stent characteristics. Over a mean follow-up of 4.4+/-2.1 months, 12
patients (10.1%) had 16 events (13.4%). Two patients had adverse events after
early MRI scan (4.3%), a rate that is lower than the event rate in the patients
who did not undergo MRI (16%, P=0.04), and one of the two events was clearly not
MRI related. CONCLUSION: CMR on a 1.5T scanner can be safely performed within one
to seven days after coronary bare-metal stent implantation and is not associated
with an increased risk of adverse clinical cardiac outcomes. In the light of
accumulating data, the guidelines by stent manufacturers should be revised.
PMID- 17036358
TI - Fluid-attenuated inversion-recovery SSFP imaging.
AB - PURPOSE: To describe and evaluate a fast, fluid-suppressed 2D multislice steady
state free precession (SSFP) neuroimaging sequence. MATERIALS AND METHODS: We
developed a fast fluid-attenuated inversion-recovery SSFP sequence for use in
neuroimaging. The inversion time (TI) was optimized to yield good cerebrospinal
fluid (CSF) suppression while conserving white matter (WM)/lesion contrast across
a broad range of flip angles. Multiple SSFP acquisitions were combined using the
sum-of-squares (SOS) method to maximize SNR efficiency while minimizing SSFP
banding artifacts. We compared our fluid-attenuated inversion-recovery (FLAIR)
SSFP sequence with FLAIR fast spin-echo (FSE) in both normal subjects and a
volunteer with multiple sclerosis. SNR measurements were performed to ascertain
the SNR efficiency of each sequence. RESULTS: Our FLAIR SSFP sequence
demonstrated excellent CSF suppression and good gray matter (GM)/WM contrast.
Coverage of the entire brain (5-mm slices, 24-cm FOV, 256 x 192 matrix) was
achieved with FLAIR SSFP in less than half the scan time of a corresponding FLAIR
FSE sequence with similar SNR, yielding improvements of more than 50% in SNR
efficiency. Axial scans of a volunteer with multiple sclerosis show clearly
visible plaques and very good visualization of brain parenchyma. CONCLUSION: We
have demonstrated the feasibility of a very fast fluid-suppressed neuroimaging
technique using SSFP.
PMID- 17036359
TI - EEG-fMRI using z-shimming in patients with temporal lobe epilepsy.
AB - PURPOSE: To use z-shimming, a technique that reduces signal loss due to
susceptibility artifacts that can result in reduced or absent activation in
electroencephalography (EEG) functional MRI (fMRI) sessions in patients with
temporal lobe epilepsy (TLE), to determine whether it would result in an
increased ability to detect significant regions of blood oxygenation level
dependent (BOLD) signal change. MATERIALS AND METHODS: Eight patients with TL EEG
spikes underwent an EEG-fMRI scanning session using z-shimming. The signal
intensities in the z-shimmed images were compared with those in the standard
images. BOLD activation maps were created from the two sets of images using the
timings of the spikes observed on the EEG. RESULTS: The mean signal increase in
the TLs as a result of z-shimming was 45.9%+/-4.5%. The percentage of TL voxels
above a brain intensity threshold rose from 66.1%+/-7.6% to 77.6%+/-5.7%. This
appreciable increase in signal did not lead to any significant differences in the
statistical maps created with the two sets of functional images. CONCLUSION: The
results suggest that loss of signal is not the limiting factor for the detection
of spike-related BOLD signal changes in patients with TLE activity.
PMID- 17036360
TI - An unusual cause of susceptibility artifact in magnetic resonance imaging.
AB - Magnetic susceptibility artifact has been documented with various implants and
devices, which require appropriate identification with screening of patients
prior to subjecting them to magnetic resonance examination. We performed
cardiovascular magnetic resonance (CMR) examination of the aorta in a 24-year-old
woman in the setting of repaired aortic coarctation, and found magnetic
susceptibility artifact arising from the stomach in the absence of known
susceptibility artifact-producing material in this region. Further history
revealed that she had ingested a prenatal vitamin prior to imaging, prompting
experimental analyses that led us to conclude that iron-containing vitamins may
be a source of magnetic susceptibility artifact.
PMID- 17036361
TI - Prognostic significance of [(18)F]fluorodeoxyglucose uptake on positron emission
tomography in patients with pathologic stage I lung adenocarcinoma.
AB - BACKGROUND: [(18)F]Fluoro-2-deoxyglucose uptake on positron emission tomography
(FDG-PET) has been frequently used for diagnosis and staging of lung cancer. The
prognostic significance of FDG uptake on PET was evaluated in patients with
pathologic Stage I lung adenocarcinoma (tumor stages were based on the TNM
classification of the International Union Against Cancer). METHODS: Disease-free
survival of 98 patients with pathologic Stage I lung adenocarcinoma who were
treated by curative resection was examined in relation to sex, age, histologic
grade of differentiation, surgical procedure, tumor stage, and FDG uptake
measured as the maximum standardized uptake value (SUV). RESULTS: Sixty-three
patients were had Stage IA disease and 35 patients had Stage IB disease. Six
patients each with Stage IA and Stage IB disease developed disease recurrence
after a mean postsurgical follow-up period of 31 months. Ten (23%) of the 43
patients with SUV > or = 3.3 developed a recurrence compared with 2 (4%) of the
55 patients with SUV < 3.3 (P = .020). Ten (20%) of the 51 patients with
moderately or poorly differentiated adenocarcinoma developed disease recurrence,
compared with 2 (4%) of the 47 patients with well-differentiated adenocarcinoma
(P = .056). Multivariate analysis demonstrated that histologic grade of
differentiation was not correlated with the frequency of tumor recurrence (P =
.286), whereas SUV was found to be marginally correlated (P = .079). CONCLUSIONS:
FDG uptake appears to be predictive of disease-free survival in patients with
Stage I lung adenocarcinoma. FDG uptake could yield important information for
determining the likely value of postoperative adjuvant chemotherapy in such
patients.
PMID- 17036363
TI - Immunotoxic effects of chemicals: A matrix for occupational and environmental
epidemiological studies.
AB - BACKGROUND: Many biological and chemical agents have the capacity to alter the
way the immune system functions in human and animals. This study evaluates the
immunotoxicity of 20 substances used widely in work environments. METHODS: A
systematic literature search on the immunotoxicity of 20 chemicals was performed.
The first step was to review literature on immunotoxicity testing and testing
schemes adopted for establishing immunotoxicity in humans. The second step
consisted of providing a documentation on immunotoxicity of substances that are
widely used in work environment, by building tables for each chemical of interest
(benzene, trichloroethylene, PAHs, crystalline silica, diesel exhausts, welding
fumes, asbestos, styrene, formaldehyde, toluene, vinyl chloride monomer,
tetrachloroethylene, chlorophenols, 1,3-butadiene, mineral oils, P
dichlorobenzene, dichloromethane, xylene, 1,1,1-trichloroethane, ethylene oxide).
The third step was the classification of substances; an index (strong,
intermediate, weak, nil) was assigned on the basis of the evidence of toxicity
and type of immunotoxic effects (immunosuppression, autoimmunity,
hypersensitivity) on the basis of the immune responses. Finally substances were
assigned a score of immunotoxic power. RESULTS: Tables have been produced that
include information for the 20 substances of interest, based on 227 animal
studies and 94 human studies. Each substance was assigned an index of immunotoxic
evidence, a score of immunotoxic power and type of immunotoxic effect.
CONCLUSIONS: This matrix can represent a tool to identify chemicals with similar
properties concerning the toxicity for the immune system, and to interpret
epidemiological studies on immune-related diseases.
PMID- 17036362
TI - Biomarkers of depression in cancer patients.
AB - BACKGROUND: Inflammation and perturbation of the hypothalamic-pituitary-adrenal
(HPA) axis function appears to play a putative role in the etiology of
depression. Patients with metastatic cancer demonstrate elevated prevalence rates
for depression. The objective of the current study was to illustrate the efficacy
of interleukin-6 (IL-6) and HPA axis function as adjuncts to support the
diagnosis of depression in cancer patients. METHODS: Plasma concentrations of IL
6 and cortisol were measured in 114 cancer patients with and without depression.
The relative diurnal variation of cortisol (cortisol VAR), expressed as a
percentage, was calculated. Receiver operating characteristics analysis was
performed. RESULTS: Depression was associated with increased plasma
concentrations of IL-6 (18.7 pg/mL vs. 2.7 pg/mL; P < .001) and higher cortisol
concentrations at 8 AM and 8 PM. The relative cortisol VAR (11.7% vs. 60.6%,
respectively; P < .001) was found to be decreased in cancer patients with
depression, indicating a disturbed circadian function of the HPA axis. As a
biomarker of depression, IL-6 yielded at a cutoff value of 10.6 pg/mL, a
sensitivity of 79%, and a specificity of 87% (area under the curve [AUC] = 0.86;
95% confidence interval [95% CI], 0.78-0.94), whereas cortisol VAR demonstrated a
sensitivity of 81% and a specificity of 88% (AUC = 0.85; 95% CI, 0.74-0.97) at a
cutoff value of 33.5%. CONCLUSIONS: Depression is associated with increased
plasma IL-6 concentrations in patients with cancer. These patients demonstrate a
dysfunction of the HPA-axis, characterized by a decreased diurnal variation of
cortisol. The high sensitivity and specificity of these parameters biomarkers of
depression make IL-6 and cortisol VAR helpful tools in the diagnosis of
depression in patients with cancer.
PMID- 17036364
TI - The Declaration of Brescia on prevention of the neurotoxicity of metals June 18,
2006.
PMID- 17036365
TI - Fungal biofiltration of alpha-pinene: effects of temperature, relative humidity,
and transient loads.
AB - Over the past decade much effort has been made to develop new carrier materials,
more performant biocatalysts, and new types of bioreactors for waste gas
treatment. In biofilters fungal biocatalysts are more resistant to acid and dry
conditions and take up hydrophobic compounds from the gas phase more easily than
wet bacterial biofilms. In the present study, a biofilter packed with a mixture
of perlite and Pall rings and fed alpha-pinene-polluted air was inoculated with a
new fungal isolate identified as Ophiostoma species. alpha-Pinene is a volatile
pollutant typically found in waste gases from wood-related industries. The
temperature of waste gas streams from pulp and paper industries containing alpha
pinene is usually higher than ambient temperature. Studies were undertaken here
on the effect on performance of temperature changes in the range of 15-40 degrees
C. The effect of temperature on biodegradation kinetics in continuous reactors
was elucidated through equations derived from the Arrhenius formula. Moreover,
the effects of the relative humidity (RH) of the inlet gas phase, transient loads
(shock or starvation), and the nature of the nitrogen source on alpha-pinene
removal were also studied in this research. The results suggest that the fungal
biofilter appears to be an effective treatment process for the removal of alpha
pinene. The optimal conditions are: temperature around 30 degrees C, RH of the
inlet waste gas stream around 85%, and nitrate as nitrogen source. The fungal
biofilter also showed a good potential to withstand shock loads and recovered
rapidly its full performance after a 3-7 days starvation period.
PMID- 17036366
TI - All-cause mortality associated with atypical and typical antipsychotics in
demented outpatients.
AB - PURPOSE: To estimate the association between use of typical and atypical
antipsychotics and all-cause mortality in a population of demented outpatients.
METHODS: The study cohort comprised all demented patients older than 65 years and
registered in the Integrated Primary Care Information (IPCI) database, during
1996-2004. First, mortality rates were calculated during use of atypical and
typical antipsychotics. Second, we assessed the association between use of
atypical and typical antipsychotics and all-cause mortality through a nested case
control study in the cohort of demented patients. Each case was matched to all
eligible controls at the date of death by age and duration of dementia. Odds
ratios were estimated through conditional logistic regression analyses. RESULTS:
The crude mortality rate was 30.1 (95%CI: 18.2-47.1) and 25.2 (21.0-29.8) per 100
person-years (PY) during use of atypical and typical antipsychotics,
respectively. No significant difference in risk of death was observed between
current users of atypical and typical antipsychotics (OR = 1.3; 95%CI: 0.7-2.4).
Both types of antipsychotics were associated with a significantly increased risk
of death as compared to non-users (OR = 2.2, 1.2-3.9 for atypical antipsychotics;
OR=1.7, 1.3-2.2 for typical antipsychotics). CONCLUSIONS: Conventional
antipsychotic drug should be included in the FDA's Public Health advisory, which
currently warns only of the increased risk of death with the use of atypical
antipsychotics in elderly demented persons.
PMID- 17036367
TI - Synthesis and anti-tumor activities of novel pyrazolo[1,5-a]pyrimidines.
AB - A series of novel pyrazolo[1,5-a]pyrimidines were designed and synthesized in
order to find novel potent anti-tumor compounds. The structures of all the
compounds were confirmed by IR, (1)H-NMR, elemental analysis, and MS. Their anti
tumor activities against cancer cell lines were tested by the MTT method in
vitro. Compound 19 displayed potent anti-tumor activity.
PMID- 17036368
TI - Synthesis and antibacterial activity of nitroaryl thiadiazole-levofloxacin
hybrids.
AB - Novel levofloxacin-containing hybrids carrying a 5-(nitroaryl)-1,3,4-thiadiazol-2
yl group were synthesized and evaluated in vitro against Gram-positive and Gram
negative bacteria. Preliminary data indicated that levofloxacin-nitrofuran and
levofloxacin-nitroimidazole hybrids have a potent activity against Gram-positive
organisms with enhanced anti-staphylococcal activity compared with the parent
quinolone (N-desmethyl levofloxacin).
PMID- 17036369
TI - Novel synthesis of 1,3,4-thiadiazine derivatives and their cycloaddition
reactions.
AB - 4-Phenyl-3-thiosemicarbazide 1 reacted with the alpha-halocarbonyl compounds 2a,
b to give the thiosemicarbazone derivatives 3a, b. The latter compounds underwent
cyclization to the 1,3,4-thiadiazine derivatives 4a, b which underwent [2 + 4]
cycloaddition reactions to give the 4H-thiopyran derivatives 7a, b. The chemistry
of these thiopyrans was studied. Some of the fused derivatives among them
compounds 20a, 20b, 21a, 21b allowed good mycelial growth and sporulation by the
two fungi. This indicates that the two fungi can use the N-containing
heterocyclic ring as a nitrogen source.
PMID- 17036370
TI - The tubulin-bound conformation of discodermolide derived by NMR studies in
solution supports a common pharmacophore model for epothilone and discodermolide.
PMID- 17036371
TI - Catalytic, asymmetric synthesis of 1,4-benzoxazinones: a remarkably
enantioselective route to alpha-amino acid derivatives from o-benzoquinone
imides.
PMID- 17036372
TI - Complete assignments 1H and 13C NMR spectral data of four anabaseine derivatives.
AB - The anabaseine derivatives 6-methoxy-7-hydroxy-1-(pyridin-3-yl)-3,4
dihydroisoquinoline, 6,7-dimethoxy-1-(pyridin-3-yl)-1,2,3,4
tetrahydroisoquinoline and 6,7-dimethoxy-1-(piperidin-3-yl)-1,2,3,4
tetrahydroisoquino- line were prepared either by demethylation with HBr or by
reduction with different reagents, NaBH4 and H2/PtO2 from 6,7-dimethoxy-1
(pyridin-3-yl)-3,4-dihydroisoquinoline, as starting material. The structures have
been fully assigned by the combination of one- and two-dimensional experiments.
PMID- 17036373
TI - Changes in medication associated with epilepsy-related hospitalisation: a case
crossover study.
AB - AIM: To assess the association between changes in medication and epilepsy-related
hospitalisation. METHODS: Data were obtained from the PHARMO Record Linkage
System (Jan 1998 to Dec 2002). We conducted a case-crossover study among patients
with a first epilepsy-related hospital admission who had continuously used at
least one antiepileptic drug (AED) during a 28-week period before admission. For
each patient, changes in medication in a 28-day window before hospitalisation
were compared with changes in four earlier 28-day windows. Evaluated changes
were: changes in AEDs (pattern and dosage), changes in interacting co-medication
and changes in non-interacting co-medication (i.e. introduction of non
interacting drugs). The strength of the association between changes in medication
and epilepsy-related hospitalisation was estimated using conditional logistic
regression analysis and expressed as odds ratios (ORs) with 95% confidence
intervals (CI). RESULTS: Out of 1185 patients with a first epilepsy-related
hospitalisation, 217 patients met the inclusion criteria. Of the changes in
antiepileptic therapy, discontinuation showed a trend towards an increased risk
of hospitalisation (OR: 2.57; 95%CI: 0.81-8.17). Drug interactions influencing
antiepileptic therapy rarely occurred. Introduction of three or more non
interacting drugs was significantly associated with epilepsy-related
hospitalisation (OR: 4.80; 95%CI: 2.12-10.87). Of individual drugs, addition of
antimicrobial agents was significantly associated with epilepsy-related
hospitalisation (OR: 1.99; 95%CI: 1.06-3.75). CONCLUSIONS: Changes in AED therapy
were not significantly associated with epilepsy-related hospitalisation and few
drug interactions influencing antiepileptic therapy occurred. However, patients
starting three or more new non-AEDs had a nearly five times increased risk of
epilepsy-related hospital admission.
PMID- 17036374
TI - Myeloablative chemotherapy followed by autologous stem cell infusion may overcome
the adverse prognostic impact of FLT3 (foetal liver tyrosine kinase 3) mutations
in patients with acute myeloid leukaemia and normal karyotype.
AB - In this study, we analysed the prognostic relevance of foetal liver tyrosine
kinase 3 (FLT3) mutations in 73 patients with acute myeloid leukaemia (AML) with
normal karyotype, who survived induction and consolidation and received
autologous stem cell transplantation (ASCT) after successful mobilization of
peripheral blood stem cell (PBSC). There were 44 males and 29 females with a
median age of 54 years (range 20-77). Overall, 16 out of 73 autografted patients
(22%) had FLT3 mutations. More in detail, FLT3/ITDs were detected in 10 out of 73
patients (14%), while FLT3 D835 mutations were detected in five cases (7%). One
patient (1%) was found as having both abnormalities. White blood cell count
(p=0.009), serum concentration of lactate dehydrogenase (p=0.01), and percentages
of peripheral blood (p=0.002) and bone marrow blasts (p=0.03) were significantly
higher in patients showing the FLT3 mutations. On the contrary, overall survival
and disease-free survival were similar between patients with or without FLT3
mutations (p=0.73 and 0.78, respectively). In conclusion, our data suggest that
myeloablative chemotherapy supported by auto-PBSCT may overcome the adverse
prognostic implications of FLT3 mutations in AML. However, it is to consider that
autografted patients are highly selected for best response to induction,
consolidation and mobilization, as well as for minor non-haematologic toxicity.
PMID- 17036375
TI - Relevance of Ras gene mutations in the context of the molecular heterogeneity of
multiple myeloma.
AB - Ras gene mutations are a recurrent genetic lesion in multiple myeloma (MM). Here,
we report a mutation analysis of N- and K-Ras genes in purified plasma cell
populations from a panel of 81 newly diagnosed MM patients stratified according
to the most frequent genetic and molecular features associated with the
neoplasia. Ras gene mutations, mostly involving the N-Ras gene, were detected in
20% of the patients. Ras mutations did not correlate with the presence of
chromosome 13q deletion, trisomy of chromosome 11, 1q amplification or
hyperdiploidy. In addition, despite an appreciable association with tumours
overexpressing Cyclin D1, Ras mutations did not correlate at significant levels
with any of the proposed groups in the TC classification, based on the presence
of the major IgH chromosomal translocations and expression of Cyclin D genes.
Finally, transcription analyses revealed the presence of differentially expressed
transcripts in human multiple myeloma cell lines carrying the Ras gene mutations
but not in primary tumours. Overall, these data suggest that Ras gene mutations
are not likely to represent a master lesion in MM but its relevance needs to be
considered in the context of other genetic abnormalities.
PMID- 17036376
TI - Fertility among female hodgkin lymphoma survivors attempting pregnancy following
ABVD chemotherapy.
AB - Although ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy is
infrequently associated with premature amenorrhea, little is known about the
success rate of women attempting pregnancy following ABVD. In the present study
females treated for HL with ABVD chemotherapy without pelvic radiation therapy
(RT) and who were alive without relapse > or =3 years after treatment were
identified from a clinical database and screened for inclusion. Using a
standardized questionnaire, we determined the pregnancy rate (i.e. time-to
pregnancy, TTP) among survivors who had become pregnant, tried to become
pregnant, or who had been sexually active for over 2 months without using
contraception at any time following ABVD. The cumulative incidence of pregnancy
was calculated using the Kaplan-Meier method. Cox proportional hazards models
were constructed to compare the pregnancy rate among HL survivors to that
reported by friend or sibling controls. Thirty-six female HL survivors, who had
attempted pregnancy after ABVD treatment, and 29 controls, completed the survey.
Eighteen patients (50%) received 2-4 cycles of ABVD, 16 (44%) received 4-6
cycles, and 2 (6%) received >6 cycles. The median TTP among both HL survivors and
controls was 2.0 months. The 12-month pregnancy rates were 70% and 75%,
respectively. The fertility ratio (FR) for HL survivors versus controls was 0.94
(95%CI = 0.53-1.66; p = 0.84) after adjusting for age and frequency of
intercourse (where FR < 1 indicates subfertility). Age at treatment and the
number of cycles of chemotherapy were not associated with pregnancy rate among HL
survivors. Female HL patients who had survived without recurrence > or =3 years
and who had attempted pregnancy after ABVD did not experience significant sub
fertility.
PMID- 17036378
TI - Heavy smoking and liver.
AB - Smoking causes a variety of adverse effects on organs that have no direct contact
with the smoke itself such as the liver. It induces three major adverse effects
on the liver: direct or indirect toxic effects, immunological effects and
oncogenic effects. Smoking yields chemical substances with cytotoxic potential
which increase necro-inflammation and fibrosis. In addition, smoking increases
the production of pro-inflammatory cytokines (IL-1, IL-6 and TNF- alpha) that
would be involved in liver cell injury. It contributes to the development of
secondary polycythemia and in turn to increased red cell mass and turnover which
might be a contributing factor to secondary iron overload disease promoting
oxidative stress of hepatocytes. Increased red cell mass and turnover are
associated with increased purine catabolism which promotes excessive production
of uric acid. Smoking affects both cell-mediated and humoral immune responses by
blocking lymphocyte proliferation and inducing apoptosis of lymphocytes. Smoking
also increases serum and hepatic iron which induce oxidative stress and lipid
peroxidation that lead to activation of stellate cells and development of
fibrosis. Smoking yields chemicals with oncogenic potential that increase the
risk of hepatocellular carcinoma (HCC) in patients with viral hepatitis and are
independent of viral infection as well. Tobacco smoking has been associated with
suppression of p53 (tumour suppressor gene). In addition, smoking causes
suppression of T-cell responses and is associated with decreased surveillance for
tumour cells. Moreover, it has been reported that heavy smoking affects the
sustained virological response to interferon (IFN) therapy in hepatitis C
patients which can be improved by repeated phlebotomy. Smoker's syndrome is a
clinico-pathological condition where patients complain of episodes of facial
flushing, warmth of the palms and soles of feet, throbbing headache, fullness in
the head, dizziness, lethargy, prickling sensation, pruritus and arthralgia.
PMID- 17036377
TI - Gene therapy of liver cancer.
AB - The application of gene transfer technologies to the treatment of cancer has led
to the development of new experimental approaches like gene directed enzyme/pro
drug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor
genes. In addition, gene therapy has a big impact on other fields like cancer
immunotherapy, anti-angiogenic therapy and virotherapy. These strategies are
being evaluated for the treatment of primary and metastatic liver cancer and some
of them have reached clinical phases. We present a review on the basis and the
actual status of gene therapy approaches applied to liver cancer.
PMID- 17036379
TI - Recent trends in the epidemiology of inflammatory bowel diseases: up or down?
AB - Inflammatory bowel disease (IBD) is traditionally considered to be common in the
Western world, and its incidence has sharply increased since the early 1950s. In
contrast, until the last decade, low prevalence and incidence rates have been
reported from other parts of the world including Eastern Europe, South America,
Asia and the Pacific region. Recent trends indicate a change in the epidemiology
of IBD with previously low incidence areas now reporting a progressive rise in
the incidence, while in West European and North American countries the figures
have stabilized or slightly increased, with decreasing incidence rates for
ulcerative colitis. Some of these changes may represent differences in diagnostic
practices and increasing awareness of the disease. The quality of studies is also
variable. Additional epidemiologic studies are needed to better define the burden
of illness, explore the mechanism of association with environmental factors, and
identify new risk factors.
PMID- 17036380
TI - Elevated risk for gastric adenocarcinoma can be predicted from histomorphology.
AB - The number of patients with gastric cancer has more than doubled since 1985 in
developing countries. Thus, the questions of whether it can be predicted from
gastritis morphology, who is at risk and who has a lower risk of developing
gastric carcinoma are raised. H pylori-infection leads to erosions, ulcerations,
carcinoma, mucosa associated lymphoid tissue (MALT)-lymphoma and extragastric
diseases only in some individuals. The frequency of ulcerations among H pylori
infected individuals is estimated to be 13%, gastric cancer about 1% and MALT
lymphoma around 0.1%. In the literature a multistep model from chronic active H
pylori-infection through multifocal atrophy, intestinal metaplasia, dysplasia
(intraepithelial neoplasia) and carcinoma has been described. But this model
cannot be applied to all routine cases. Since risk factors such as metaplasia and
atrophy are paracancerous rather than precancerous conditions, this raises the
question whether there is a better morphological marker. Differences in
topography, grade and activity of Helicobacter gastritis in the antrum and corpus
might be good markers for identifying those who are at risk of developing gastric
cancer. It is known that the so-called corpus dominant H pylori gastritis is
found more frequently among individuals with early and advanced gastric cancer
and within high risk populations. This is valid both for first-degree relatives
of gastric cancer patients and for patients with gastric adenoma and hyperplastic
polyps. In conclusion, corpus-dominant H pylori gastritis is significantly more
common in patients with advanced and early gastric cancer, first-degree relatives
of patients with gastric cancer, patients with gastric adenoma and gastric
hyperplastic polyps. Therefore, all these patients are at risk of developing
gastric cancer. Next, the question of who is at risk of developing corpus
dominant gastritis is raised. It appears that patients with a low acid output
more frequently develop gastric cancer. Eradication therapy is never performed
too early but probably sometimes too late after the patients pass a "point of no
return". Large prospective long term studies are necessary to prove this and
identify new reliable markers for gastric cancer development.
PMID- 17036382
TI - Management of pseudomyxoma peritonei.
AB - Pseudomyxoma peritonei (PMP) is a rare disease. It refers to a progressive
disease process within the peritoneum which originates from the appendix or
ovaries and is characterised by the production of copious amounts of mucinous
fluid resulting in a "jelly belly". If untreated the condition is fatal. The
traditional approach to PMP is based on repeated surgical debulking procedures,
often associated with intraperitoneal or systemic chemotherapy. The natural
history of this disease has been drastically modified since the introduction of a
new surgical approach defined as a peritonectomy procedure. This paper is to
review the literature on this treatment strategy.
PMID- 17036383
TI - Total plasma homocysteine and methylenetetrahydrofolate reductase C677T
polymorphism in patients with colorectal carcinoma.
AB - AIM: To investigate the behaviour of total plasma homocysteine (tHcy) and its
most common genetic determinant defect, the methylenetetrahydrofolate reductase
C677T (C677TMTHFR) polymorphism in patients with early stage colorectal
carcinoma. METHODS: tHcy was quantified by Abbott IMx immunoassay; screening for
C677TMTHFR substitution was performed by PCR and restriction analysis. RESULTS:
The frequency of the C/T and T/T genotypes of the C677TMTHFR gene polymorphism
did not differ between the groups. The mean tHcy was statistically higher in
cancer patients than in control subjects carrying the same C/C or C/T genotype,
whereas there was no difference in the T/T homozygous carriers of the two groups.
tHcy was significantly higher in the T/T homozygous carriers than in C/C and C/T
genotype carriers. CONCLUSION: The statistically significant increase of tHcy
observed in C/C and C/T genotype carriers among our cancer patients is related to
substrate consumption dependent on the tumor cell proliferation rate, whereas the
tHcy increase observed in T/T genotype carriers of both groups probably depends
on the enzymatic deficit of the homocysteine conversion to methionine and/or on
the folate deficiency.
PMID- 17036381
TI - Indications for 5-aminosalicylate in inflammatory bowel disease: is the body of
evidence complete?
AB - Mesalazine is a safe drug, although adverse events may be seen in a minority of
patients. This applies also to pregnant women and children. The role of
mesalazine in combination therapy to improve efficacy and concomitant drug
pharmacokinetics, or in chemoprevention against inflammatory bowel disease (IBD)
related colonic carcinoma has not yet been completely elucidated. Therapeutic
success of mesalazine may be optimized by a combination of high dose and low
frequency of dosage to improve compliance. Therefore, due to its superior safety
profile and pharmacokinetic characteristics, mesalazine is preferable to
sulphasalazine. This paper reviews the literature concerning mechanisms of
action, indications and off-label use, pharmacokinetic properties and
formulations, therapeutic efficacy, compliance, paediatric indications,
chemoprevention, and safety issues and adverse event profile of mesalazine
treatment versus sulphasalazine. It also highlights these controversies in order
to clarify the potential benefits of mesalazines in IBD therapy and evidence for
its use.
PMID- 17036384
TI - Distinct patterns of mucosal apoptosis in H pylori-associated gastric ulcer are
associated with altered FasL and perforin cytotoxic pathways.
AB - AIM: To analyze the level of apoptosis in different mucosal compartments and the
differential expression of Fas/Fas-ligand and perforin in H pylori-associated
gastric ulcer. METHODS: Antral specimens from patients with H pylori-related
active gastric ulcer (GU), H pylori-related gastritis, and non-infected controls
were analysed for densities and distribution of apoptotic cells determined by the
TdT-mediated dUDP-biotin nick-end-labelling method. GU patients were submitted to
eradication therapy with follow-up biopsy after 60 d. Fas, FasL, and perforin
expressing cells were assessed by immunoperoxidase, and with anti-CD3, anti-CD20
and anti-CD68 by double immunofluorescence and confocal microscopy. Quantitative
analysis was performed using a computer-assisted image analyser. RESULTS: H
pylori-infected antrum showed greater surface epithelial apoptosis which
decreased after eradication therapy. In the lamina propria, higher rates of
mononuclear cell apoptosis were observed in H pylori-gastritis. Co-expression of
Fas with T-cell and macrophage markers was reduced in GU. FasL- and perforin
expressing cells were increased in H pylori-infection and correlated with
epithelial apoptosis. Perforin-expressing cells were also increased in GU
compared with H pylori-gastritis. CONCLUSION: Epithelial apoptosis is increased
in H pylori-infection and correlates to FasL- and perforin-expression by T cells.
Expression of perforin is correlated with the tissue damage, and may represent
the enhancement of a distinct cytotoxic pathway in GU. Increased expression of
FasL not paralleled by Fas on T-cells and macrophages may indicate a reduced
susceptibility to the Fas/FasL-mediated apoptosis of lymphoid cells in H pylori
infection.
PMID- 17036385
TI - An herbal formula, CGX, exerts hepatotherapeutic effects on dimethylnitrosamine
induced chronic liver injury model in rats.
AB - AIM: To evaluate the therapeutic effect of Chunggan extract (CGX), a modified
traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine (DMN)
induced chronic liver injury model in rats. METHODS: Liver injuries were induced
in Wistar rats by injection of DMN (ip, 10 mg/mL per kg) for 3 consecutive days
per week for 4 wk. The rats were administered with CGX (po, 100 or 200 mg/kg per
day) or distilled water as a control daily for 4 wk starting from the 15(th) d of
the DMN treatment. Biochemical parameters (serum albumin, bilirubin, ALP, AST and
ALT), lipid peroxides, hydroxyproline, as well as histological changes in liver
tissues were analyzed. In addition, gene expression of TNF-alpha, TGF-beta, TIMP
1, TIMP-2, PDGF-beta, and MMP-2, all of which are known to be associated with
liver fibrosis, were analyzed using real-time PCR. RESULTS: CGX administration
restored the spleen weight to normal after having been increased by DMN
treatment. Biochemical analysis of the serum demonstrated that CGX significantly
decreased the serum level of ALP (P < 0.05), ALT (P < 0.01), and AST (P < 0.01)
that had been elevated by DMN treatment. CGX administration moderately lowered
lipid peroxide production and markedly lowered hydroxyproline generation caused
by DMN treatment in accordance with histopathological examination. DMN treatment
induced a highly up-regulated expression of TNF-alpha, TGF-beta, TIMP-1, TIMP-2,
PDGF-beta, and MMP-2. Of these, the gene expression encoding PDGF-beta and MMP-2
was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and
was remarkably ameliorated by CGX administration. CONCLUSION: CGX exhibits
hepatotherapeutic proper-ties against chronic hepatocellular destruction and
consequential liver fibrosis.
PMID- 17036387
TI - Role of vasoactive intestinal peptide and nitric oxide in the modulation of
electroacupucture on gastric motility in stressed rats.
AB - AIM: To investigate the effects and mechanisms of vasoactive intestinal peptide
(VIP) and nitric oxide (NO) in the modulation of electroacupucture (EA) on
gastric motility in restrained-cold stressed rats. METHODS: An animal model of
gastric motility disorder was established by restrained-cold stress. Gastric
myoelectric activities were recorded by electrogastroenterography (EGG). VIP and
NO concentrations in plasma and gastric mucosal and bulb tissues were detected by
radioimmunoassay (RIA). VIP expression in the gastric walls was assayed using
avidin-biotin-peroxidase complex (ABC) and image analysis. RESULTS: In cold
restrained stressed rats, EGG was disordered and irregular. The frequency and
amplitude of gastric motility were higher than that in control group (P < 0.01).
VIP and NO contents of plasma, gastric mucosal and bulb tissues were obviously
decreased (P < 0.01). Following EA at "Zusanli" (ST36), the frequency and
amplitude of gastric motility were obviously lowered (P < 0.01), while the levels
of VIP and NO in plasma, gastric mucosal and bulb tissues increased strikingly (P
< 0.01, P < 0.05) and expression of VIP in antral smooth muscle was elevated
significantly (P < 0.01) in comparison with those of model group. CONCLUSION: VIP
and NO participate in the modulatory effect of EA on gastric motility. EA at
"Zusanli" acupoint (ST36) can improve gastric motility of the stressed rats by
increasing the levels of VIP and NO.
PMID- 17036386
TI - Hydrodynamics based transfection in normal and fibrotic rats.
AB - AIM: Hydrodynamics based transfection (HBT), the injection of a large volume of
naked plasmid DNA in a short time is a relatively simple, efficient and safe
method for in vivo transfection of liver cells. Though used for quite some time,
the mechanism of gene transfection has not yet been elucidated. METHODS: A
luciferase encoding plasmid was injected using the hydrodynamics based procedure
into normal and thioacetamide-induced fibrotic Sprague Dawley rats. Scanning and
transmission electron microscopy images were taken. The consequence of a dual
injection of Ringer solution and luciferase pDNA was followed. Halofuginone, an
anti collagen type I inhibitor was used to reduce ECM load in fibrotic rats prior
to the hydrodynamic injection. RESULTS: Large endothelial gaps formed as soon as
10' following hydrodynamic injection; these gradually returned to normal 10 d
post injection. Hydrodynamic administration of Ringer 10 or 30 m prior to
moderate injection of plasmid did not result in efficient transfection suggesting
that endothelial gaps by themselves are not sufficient for gene expression. Gene
transfection following hydrodynamic injection in thioacetamide induced fibrotic
rats was diminished coinciding with the level of fibrosis. Halofuginone, a
specific collagen type I inhibitor, alleviated this effect. CONCLUSION: The
hydrodynamic pressure formed following HBT results in the formation of large
endothelial gaps. These gaps, though important in the transfer of DNA molecules
from the blood to the space of Disse are not enough to provide the appropriate
conditions for hepatocyte transfection. Hydrodynamics based injection is
applicable in fibrotic rats provided that ECM load is reduced.
PMID- 17036388
TI - The timing of bowel preparation before colonoscopy determines the quality of
cleansing, and is a significant factor contributing to the detection of flat
lesions: a randomized study.
AB - AIM: To compare the cleansing quality of polyethylene glycol electrolyte solution
and sodium phosphate with different schedules of administration, and to evaluate
whether the timing of the administration of bowel preparation affects the
detection of polyps. METHODS: One hundred and seventy-seven consecutive
outpatients scheduled for colonoscopy were randomized in one of four groups to
receive polyethylene glycol electrolyte solution or oral sodium phosphate with
two different timing schedules. Quality of cleansing, polyp detection, and
tolerance were evaluated. RESULTS: Patients receiving polyethylene glycol or
sodium phosphate on the same day as the colonoscopy, obtained good to excellent
global cleansing scores more frequently than patients who received polyethylene
glycol or sodium phosphate on the day prior to the procedure (P < 0.001). Flat
lesions, but not flat adenomas, were more frequent in patients prepared on the
same day (P = 0.02). CONCLUSION: The quality of colonic cleansing and the
detection of flat lesions are significantly improved when the preparation is
taken on the day of the colonoscopy.
PMID- 17036389
TI - Abnormalities of uterine cervix in women with inflammatory bowel disease.
AB - AIM: To evaluate the prevalence of abnormalities of the uterine cervix in women
with inflammatory bowel disease (IBD) when compared to healthy controls. METHODS:
One hundred and sixteen patients with IBD [64 with Crohn's disease (CD) and 52
with ulcerative colitis (UC)] were matched to 116 healthy controls by age (+/- 2
years) at the time of most recent papanicolaou (Pap) smear. Data collected
consisted of age, race, marital status, number of pregnancies,
abortions/miscarriages, duration and severity of IBD, Pap smear results within
five years of enrollment, and treatment with immunosuppressive drugs. Pap smear
results were categorized as normal or abnormal including atypical squamous cells
of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion
(LGSIL), and high-grade squamous intraepithelial lesion (HGSIL). RESULTS: The
median age at the time of Pap smear was 46 (range: 17-74) years for the IBD group
and matched controls (range: 19-72 years). There were more Caucasian subjects
than other ethnicities in the IBD patient group (P = 0.025), as well as fewer
abortions (P = 0.008), but there was no significant difference regarding marital
status. Eighteen percent of IBD patients had abnormal Pap smears compared to 5%
of controls (P = 0.004). Subgroup analysis of the IBD patients revealed no
significant differences between CD and UC patients in age, ethnicity, marital
status, number of abortions, disease severity, family history of IBD, or disease
duration. No significant difference was observed in the number of abnormal Pap
smears or the use of immunosuppressive medications between CD and UC patients (P
= 0.793). No definitive observation could be made regarding HPV status, as this
was not routinely investigated during the timeframe of our study. CONCLUSION:
Diagnosis of IBD in women is related to an increased risk of abnormal Pap smear,
while type of IBD and exposure to immunosuppressive medications are not. This has
significant implications for women with IBD in that Pap smear screening protocols
should be conscientiously followed, with appropriate investigation of abnormal
results.
PMID- 17036390
TI - Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis.
AB - AIM: To report a case of severe idiopathic gastroparesis in complete absence of
Kit-positive gastric interstitial cells of Cajal (ICC). METHODS: Gastric tissue
from a patient with severe idiopathic gastroparesis unresponsive to medical
treatment and requiring surgery was analyzed by conventional histology and
immunohistochemistry. RESULTS: Gastric pacemaker cells expressing Kit receptor
had completely disappeared while the local level of stem cell factor, the
essential ligand for its development and maintenance, was increased. No signs of
cell death were observed in the pacemaker region. CONCLUSION: These results are
consistent with the hypothesis that a lack of Kit expression may lead to impaired
functioning of ICC. Total gastrectomy proves to be curative.
PMID- 17036391
TI - Polaprezinc protects human colon cells from oxidative injury induced by hydrogen
peroxide: relevant to cytoprotective heat shock proteins.
AB - AIM: To investigate the effect of polaprezinc on cellular damage induced by
hydrogen peroxide (H(2)O(2)) in human colon CaCo2 cells. METHODS: CaCo2 cells
were treated with polaprezinc (10-100 micromol/L) for 6 h. After polaprezinc
treatment, the cells were incubated with H(2)O(2) (20 micromol/L) for 1 h. Cell
viability was measured by MTT assay. Western blot analysis for heat shock protein
(HSP) 27 and HSP72 in the cells was performed. Moreover, cells were pretreated
with quercetin (200 micromol/L), an inhibitor of HSP synthesis, 2 h before
polaprezinc treatment, and cell viability and the expression of HSP27 and 72 were
assessed in these cells. RESULTS: Polaprezinc significantly protected CaCo2 cells
from cell damage induced by H(2)O(2), and up-regulated the expressions of HSP27
and HSP72 in the cells (10, 30 and 100 micromol/L of polaprezinc; 35.0% +/- 7.7%,
58.3% +/- 14.6% and 64.2% +/- 8.2%, respectively. P < 0.01 versus polaprezinc
nontreated cells; 6.0% +/- 4.4%). Quercetin inhibited the up-regulation of HSP27
and HSP72 by polaprezinc and diminished the protective effect of polaprezinc
against H(2)O(2)-caused injury in the cells. CONCLUSION: Polaprezinc is a useful
therapeutic agent for treatment of colitis and its effects depend on the function
of cytoprotective HSP in colon.
PMID- 17036392
TI - Expression of vascular endothelial growth factor and its receptors VEGFR-1 and 2
in gastrointestinal stromal tumors, leiomyomas and schwannomas.
AB - AIM: To investigate the role of vascular endothelial growth factor (VEGF) and its
receptors VEGFR-1 and 2 in the growth and differentiation of gastrointestinal
stromal tumors (GISTs). METHODS: Thirty-three GISTs, 15 leiomyomas and 6
schwannomas were examined by immunohistochemistry in this study. RESULTS: VEGF
protein was expressed in the cytoplasm of tumor cells, and VEGFR-1 and 2 were
expressed both in the cytoplasm and on the membrane of all tumors.
Immunohistochemical staining revealed that 26 GISTs (78.8%), 9 leiomyomas (60.0%)
and 3 schwannomas (50.0%) were positive for VEGF; 24 GISTs (72.7%), 12 leiomyomas
(80.0%) and 4 schwannomas (66.7%) were positive for VEGFR-1; 30 GISTs (90.9%), 5
leiomyomas (33.3%) and 4 schwannomas (66.7%) were positive for VEGFR-2. VEGFR-2
expression was statistically different between GISTs and leiomyomas (P < 0.0001).
However, there was no correlation between the expression of VEGF pathway
componenets and the clinical risk categories. CONCLUSION: Our results suggest
that the VEGF pathway may play an important role in the differentiation of GISTs,
leiomyomas and schwannomas.
PMID- 17036393
TI - Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile.
AB - AIM: To examine the presence of human papillomavirus (HPV) in esophageal squamous
cell carcinoma (ESCC) specimens collected from Colombia and Chile located in the
northern and southern ends of the continent, respectively. METHODS: We examined
47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and
Chile, respectively. HPV was detected using GP5+/GP6+ primer pair for PCR, and
confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment
was used to identify HPV genotype. In addition, P16(INK4A) protein immunostaining
of all the specimens was conducted. RESULTS: HPV was detected in 21 ESCC
specimens (29%). Sequencing analysis of L1 region fragment identified HPV-16
genome in 6 Colombian cases (13%) and in 5 Chilean cases (19%). HPV-18 was
detected in 10 cases (21%) in Colombia but not in any Chilean case. Since Chilean
ESCC cases had a higher prevalence of HPV-16 (without statistical significance),
but a significantly lower prevalence of HPV-18 than in Colombian cases (P =
0.011) even though the two countries have similar ESCC incidence rates, the
frequency of HPV-related ESCC may not be strongly affected by risk factors
affecting the incidence of ESCC. HPV-16 genome was more frequently detected in
p16 positive carcinomas, although the difference was not statistically
significant. HPV-18 detection rate did not show any association with p16
expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but
the association was not statistically significant. HPV genotypes other than HPV
16 or 18 were not detected in either country. CONCLUSION: HPV-16 and HPV-18
genotypes can be found in ESCC specimens collected from two South American
countries. Further studies on the relationship between HPV-16 presence and p16
expression in ESCC would aid understanding of the mechanism underlying the
presence of HPV in ESCC.
PMID- 17036394
TI - Expression of beta2-integrin on leukocytes in liver cirrhosis.
AB - AIM: To analyze beta2-integrin expression on blood leukocytes in liver cirrhosis.
METHODS: In 40 patients with liver cirrhosis and 20 healthy individuals, the
evaluation of expression of CD11a (LFA-1alpha), CD11b (Mac-1alpha), CD11c
(alphaX) and CD49d (VLA-4alpha) on peripheral blood leukocytes was performed
using flow cytometry. The analysis was carried out in groups of patients divided
into B and C according to Child-Pugh's classification. RESULTS: An increased
CD11a, CD11b, CD11c and CD49d integrin expression was observed on peripheral
blood leukocytes in liver cirrhosis. The integrin levels were elevated as the
advancement of liver failure progressed. The highest expression of integrins
occurred predominantly on monocytes. A slight expression of VLA-4 was found on
lymphocytes and granulocytes and it increased together with liver failure. A
positive correlation was noted between median intensity of fluorescence (MIF)
expression on polymorphonuclear cells of CD11a and CD11c and CD49d (r = 0.42, P <
0.01; r = 053, P < 0.01, respectively) in liver cirrhosis stage C. However, no
correlation was observed between integrin expression on leukocytes. The
concentrations of sICAM-1, sVCAM-1, and TNFalpha, were significantly elevated in
liver cirrhosis. CONCLUSION: beta2-integrin expression on leukocytes increases in
liver cirrhosis decompensated as the stage of liver failure increases, which is a
result of permanent activation of leukocytes circulating through the inflamed
liver environment. beta2-integrin expression on circulating leukocytes can
intensify liver cirrhosis.
PMID- 17036395
TI - Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty
liver disease.
AB - AIM: To analyze the protein expression essential for apoptosis in liver
steatosis. METHODS: The expression of proapoptotic proteins p53, Bax, and
antiapoptotic Bcl-2 in hepatocytes with steatosis (SH) and without steatosis
(NSH) was evaluated in 84 patients at various stages of non-alcoholic fatty liver
disease (NAFLD). RESULTS: Immunohistochemical staining of liver tissue showed the
activation of p53 protein in SH and NSH with increased liver steatosis,
diminished Bcl-2 and slightly decreased Bax protein. Positive correlation was
found between the stage of liver steatosis with p53 expression in SH (r = 0.54, P
< 0.01) and NSH (r = 0.49, P < 0.01). The antiapoptotic protein Bcl-2 was
diminished together with the advancement of liver steatosis, especially in non
steatosed hepatocytes (r = 0.43, P < 001). CONCLUSION: Apoptosis is one of the
most important mechanisms leading to hepatocyte elimination in NAFLD. The
intensification of inflammation in NAFLD induces proapoptotic protein p53 with
the inhibition of antiapoptotic Bcl-2.
PMID- 17036396
TI - Aggressive treatment of acute anal fissure with 0.5% nifedipine ointment prevents
its evolution to chronicity.
AB - AIM: To investigate the efficacy of topical application of 0.5% nifedipine
ointment in healing acute anal fissue and preventing its progress to chronicity.
METHODS: Thirty-one patients (10 males, 21 females) with acute anal fissure from
September 1999 to January 2005 were treated topically with 0.5% nifedipine
ointment (t.i.d.) for 8 wk. The patients were encouraged to follow a high-fiber
diet and assessed at 2, 4 and 8 wk post-treatment. The healing of fissure and any
side effects were recorded. The patients were subsequently followed up in the
outpatient clinic for one year and contacted by phone every three months
thereafter, while they were encouraged to come back if symptoms recurred.
RESULTS: Twenty-seven of the 31 patients completed the 8-wk treatment course, of
them 23 (85.2%) achieved a complete remission indicated by resolution of symptoms
and healing of fissure. Of the remaining four unhealed patients (14.8%), 2 opted
to undergo lateral sphincterotomy and the other 2 to continue therapy for four
additional weeks, resulting in healing of fissure. All the 25 patients with
complete remission had a mean follow-up of 22.9 +/- 14 (range 6-52) mo.
Recurrence of symptoms occurred in four of these 25 patients (16%) who were
successfully treated with an additional 4-wk course of 0.5% nifedipine ointment.
Two of the 27 (7.4%) patients who completed the 8-wk treatment presented with
moderate headache as a side effect of nifedipine. CONCLUSION: Topical 0.5%
nifedipine ointment, used as an agent in chemical sphincterotomy, appears to
offer a significant healing rate for acute anal fissure and might prevent its
evolution to chronicity.
PMID- 17036397
TI - Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and
increased expression in individuals from northern Brazil with gastric
adenocarcinoma.
AB - AIM: To investigate chromosome 8 numerical aberrations, C-MYC oncogene
alterations and its expression in gastric cancer and to correlate these findings
with histopathological characteristics of gastric tumors. METHODS: Specimens were
collected surgically from seven patients with gastric adenocarcinomas.
Immunostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH)
for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases
showed chromosome 8 aneuploidy and C-MYC amplification, in both the diffuse and
intestinal histopathological types of Lauren. No significant difference (P <
0.05) was observed between the level of chromosome 8 ploidy and the site, stage
or histological type of the adenocarcinomas. C-MYC high amplification, like
homogeneously stained regions (HSRs) and double minutes (DMs), was observed only
in the intestinal-type. Structural rearrangement of C-MYC, like translocation,
was observed only in the diffuse type. Regarding C-MYC gene, a significant
difference (P < 0.05) was observed between the two histological types. The C-MYC
protein was expressed in all the studied cases. In the intestinal-type the C-MYC
immunoreactivity was localized only in the nucleus and in the diffuse type in the
nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between
intestinal and diffuse types of gastric tumors support the hypothesis that these
types follow different genetic pathways.
PMID- 17036398
TI - Relationship between antioxidant capacity and oxidative stress in children with
acute hepatitis A.
AB - AIM: To investigate in children with acute hepatitis A. According to our
knowledge, there are no data about the blood levels of malondialdehyde (MDA, an
indicator of oxidative stress) and nonenzymic antioxidants in children with acute
hepatitis A. METHODS: Whole blood MDA and reduced glutathione (GSH), serum beta
carotene, retinol, vitamin E and vitamin C levels were studied in 19 (10 females,
9 males) children with acute hepatitis A and in 29 (13 females, 16 males) healthy
control subjects. RESULTS: There was a statistically significant difference
between patients and controls for all parameters (P < 0.05). Lipid peroxidation
marker MDA was significantly elevated (P < 0.001), while antioxidants beta
carotene, retinol and GSH were significantly decreased (all P < 0.001) in
patients compared to healthy subjects. In addition, alpha-tocopherol and ascorbic
acid levels were significantly lower in patients when compared to age and sex
matched controls (P < 0.05, P < 0.01, respectively). CONCLUSION: Our study shows
that hepatitis A virus induces oxidative stress in children with hepatitis A.
This finding could be taken into consideration to improve the therapeutic
approach in acute hepatitis A.
PMID- 17036399
TI - Evaluation of the use of rapid urease test: Pronto Dry to detect H pylori in
patients with dyspepsia in several cities in Indonesia.
AB - AIM: To evaluate Pronto Dry examination in patients with dyspepsia. METHODS: The
study was conducted in patients with dyspepsia who underwent endoscopic
examination in several endoscopic centers of several cities in Indonesia from
January 2003 until April 2004. Biopsies for histopathologic examination were
fixed with formalin and sent to Histopathologic Department to be analyzed and
confirm the presence of H pylori infection. If H pylori was found positive, the
density was calculated semi quantitatively. Histopathologic examination from
gastric biopsy samples was interpreted based on the updated Sydney system
classification. RESULTS: Of 550 patients, 309 (56%) were male and 241 (44%) were
female with ages ranging from 15 to 82 years. Mean age was 44.98 +/- 14.46 years.
Mean age of male patients was 44.35 +/- 13.85 years and mean age of female
patients was 45.78 +/- 15.19 years. Evaluation of endoscopic results showed
gastric ulcer in 36 cases (6.5%) and duodenal ulcer in 20 cases (3.6%). Normal
endoscopic finding was found in 45 cases (8.2%) and minimal disorder of gastritis
and duodenitis were found in 246 cases (44.7%). One case of gastric cancer was
identified. Of 56 cases which were positive based on the criteria used, 39
patients were positive with Pronto Dry and 17 patients were negative with Pronto
Dry. Overall sensitivity and specificity of Pronto Dry were 69.7% and 95.7%
respectively. Positive predictive value was 66.1% and negative predictive value
was 96.4% and overall accurate rate was 92.9%. CONCLUSION: Pronto Dry seems
promising as a diagnostic tool to detect H pylori more rapidly and accurately.
PMID- 17036400
TI - Metastatic breast cancer to the gastrointestinal tract: a case series and review
of the literature.
AB - Metastatic breast cancer involving the hepatobiliary tract or ascites secondary
to peritoneal carcinomatosis has been well described. Luminal gastrointestinal
tract involvement is less common and recognition of the range of possible
presentations is important for early and accurate diagnosis and treatment. We
report 6 patients with a variety of presentations of metastatic breast cancer of
the luminal gastrointestinal tract. These include oropharyngeal and esophageal
involvement presenting as dysphagia with one case of pseudoachalasia, a linitis
plastica-like picture with gastric narrowing and thickened folds, small bowel
obstruction and multiple strictures mimicking Crohn's disease, and a colonic
neoplasm presenting with obstruction. Lobular carcinoma, representing only 10% of
breast cancers is more likely to metastasize to the gastrointestinal tract. These
patients presented with gastrointestinal manifestations after an average of 9.5
years and as long as 20 years from initial diagnosis of breast cancer. Given the
increased survival of breast cancer patients with current therapeutic regimes,
more unusual presentations of metastatic disease, including involvement of the
gastrointestinal tract can be anticipated.
PMID- 17036401
TI - Pancreatic cancer with a high serum IgG4 concentration.
AB - Differentiation between autoimmune pancreatitis and pancreatic cancer is
sometimes difficult. It has been reported that serum IgG4 concentrations are
significantly elevated and particularly high (>135 mg/dL) in autoimmune
pancreatitis. Measurement of serum IgG4 has become a useful tool for
differentiating between autoimmune pancreatitis and pancreatic cancer. However,
we present a 74-year-old female with a markedly elevated serum IgG4 (433 mg/dL)
who underwent pancreaticoduodenectomy for pancreatic cancer. Elevated serum IgG4
levels continued after the resection. On histology, adenocarcinoma of the
pancreas accompanied with moderate lymphoplasmacytic infiltration infiltrated the
lower bile duct and duodenum, but there were no findings of autoimmune
pancreatitis. Although a small metastasis was detected in one parapancreatic
lymph node, regional lymph nodes were swollen. Abundant IgG4-positive plasma
cells infiltrated the cancerous areas of the pancreas, but only a few IgG4
positive plasma cells were detected in the noncancerous areas. Pancreatic cancer
cells were not immunoreactive for IgG4. An abundant infiltration of IgG4-positive
plasma cells was detected in the swollen regional lymph nodes and in the duodenal
mucosa. We believe that the serum IgG4 level was elevated in this patient with
pancreatic cancer as the result of an IgG4-related systemic disease that had no
clinical manifestations other than lymphadenopathy.
PMID- 17036402
TI - Biliary stone causing afferent loop syndrome and pancreatitis.
AB - We report the case of an 84-year-old female who had a partial gastrectomy with
Billroth-II anastomosis 24 years ago for a benign peptic ulcer who now presented
an acute pancreatitis secondary to an afferent loop syndrome. The syndrome was
caused by a gallstone that migrated through a cholecystoenteric fistula. This is
the first description in the literature of a biliary stone causing afferent loop
syndrome.
PMID- 17036403
TI - Propylthiouracyl-induced severe liver toxicity: an indication for alanine
aminotransferase monitoring?
AB - Propylthiouracyl (PTU)-related liver toxicity is likely to occur in about 1% of
treated patients. In case of acute or subacute hepatitis, liver failure may occur
in about one third. We report two further cases of PTU-induced subacute
hepatitis, in whom the delay between occurrence of liver damage after the
initiation of treatment, the underestimation of its severity and the delayed
withdrawal of the drug were all likely responsible for liver failure. The high
incidence of liver toxicity related to PTU, its potential severity and delayed
occurrence after initiation of treatment are in favor of monthly alanine
aminotransferase monitoring, at least during the first six months of therapy.
PMID- 17036404
TI - Acute coronary syndrome after infliximab therapy in a patient with Crohn's
disease.
AB - Infliximab is a potent anti-TNF antibody, which is used with great success in
Crohn's disease patients. Since its release in clinical practice, several adverse
reactions have been observed. The interest in possible consequences of its
administration is still high because of the recent introduction of the drug for
the long-term maintenance therapy of refractory luminal and fistulizing Crohn's
disease. We present a case of acute coronary syndrome (non-STEMI) in a patient
with corticoid resistant Crohn's disease after his first dose of infliximab. By
reviewing the scant articles that exist in the literature on this topic we made
an effort to delineate the possible mechanisms of this phenomenon.
PMID- 17036405
TI - A case of solid pseudopapillary tumor of the pancreas.
AB - We present ultrasound, computed tomography and magnetic resonance imaging
findings in a case with pancreatic solid pseudopapillary tumor and their
correlations with histopathology. Ultrasound revealed a hypoechogenic mass, and
computed tomography revealed a hypodense mass at the pancreatic head minimally
enhanced after intravenous contrast agent administration. Magnetic resonance
imaging showed a hypointense mass on unenhanced T1-weighted images including a
hyperintense focus representing the hemorrhage. The lesion was hyperintense on T2
weighted images. On the postcontrast images the lesion showed peripheral thin
contrast enhancement in arterial phase and enhanced slightly diffusely in venous
and equilibrium phases. The patient underwent elective resection of the mass and
pancreatoduodenectomy with jejunostomy tube placement. A final diagnosis of solid
pseudopapillary tumor was made histopathologically. Solid pseudopapillary tumor
is a rare pancreatic tumor. It is important to make the diagnosis preoperatively
because with an adequate surgical resection the prognosis is good. A
multimodalitary approach, especially magnetic resonance imaging can suggest the
diagnosis without the need for biopsy.
PMID- 17036406
TI - CR1/160--Invasive pulmonary aspergillosis in immuno-compromised children with
leukemia.
PMID- 17036407
TI - CR3/108--Congenital alveolar capillary dysplasia with familiary microphthalmia.
PMID- 17036408
TI - CR5/20--Acute renal failure in a child with cystic fibrosis awaiting lung
transplantation--a good outcome after all.
PMID- 17036409
TI - CR8-194--A case of fulminated fatal disseminated Varicella Zoster virus infection
with severe pulmonary damage.
PMID- 17036410
TI - CR10/80--Lymphoid interstitial pneumonia and Kabuki-Syndrome in a young man.
PMID- 17036411
TI - Mayo Clinic offers new genetic test to screen for side effects of antidepressant
treatment.
PMID- 17036412
TI - CR12/339--Nebulized cidofovir for recurrent respiratory papillomatosis: a case
report.
PMID- 17036413
TI - Whole-blood thiopurine S-methyltransferase activity with genotype concordance: a
new, simplified phenotyping assay.
AB - BACKGROUND: We have developed a new thiopurine S-methyltransferase (TPMT)
phenotyping method that measures TPMT activity in whole blood. To evaluate this
assay, we compared it with conventional TPMT phenotyping, which uses a red blood
cell (RBC) lysate and genotyping for analysis of common TPMT mutations. METHODS:
Whole-blood and RBC lysates were prepared from 402 patients' samples received for
routine analysis. The TPMT activity of lysates was determined using 6-thioguanine
as substrate with high-performance liquid chromatographic (HPLC) analysis and
fluorimetric detection. DNA was extracted from buffy coats using phenol
chloroform extraction. A multiplex amplification refractory mutation system
(ARMS) strategy was used to screen for the common TPMT mutations TPMT*2 and
TPMT*3 (TPMT*3A, TPMT*3C and TPMT*3D). RESULTS: TPMT activities were higher in
the whole-blood (mean TPMT activity 51 nmol 6-MTG/gHb/h) compared with the RBC
lysate (37 nmol 6-MTG/gHb/h). Overall, concordance with TPMT genotypic analysis
was 97% for both the new whole-blood and standard RBC lysate methods. Between low
TPMT activity and heterozygotes, both phenotypic methods gave a concordance of
79%. CONCLUSION: Using multiplex ARMS testing for TPMT*2 and 3*C mutations to
define the cut-off between low and normal TPMT activity, we have demonstrated
that the new whole-blood TPMT phenotyping method performs as well as the
conventional RBC lysate assay. This new method overcomes the need to prepare a
RBC lysate, a process which is time consuming and increases analytical variation.
The resulting assay is better suited to a regional or national TPMT phenotyping
service.
PMID- 17036415
TI - Pre-exposure prophylaxis effective.
PMID- 17036414
TI - Calculated free testosterone in men: comparison of four equations and with free
androgen index.
AB - BACKGROUND: Serum testosterone remains the most important investigation in the
diagnosis of androgen deficiency in men. Most of the circulating testosterone is
bound to albumin and sex hormone-binding globulin (SHBG), whereas free
testosterone accounts for approximately 2% of total testosterone. Because direct
measurement of free testosterone is impractical in routine practice, several
equations are used to provide clinically useful estimates of free testosterone
concentration. This study aimed to (1) obtain locally derived reference limits
for total testosterone and calculated free testosterone (CFT) concentrations, and
(2) critically evaluate the equations commonly used to estimate free
testosterone. METHODS: Serum total testosterone, SHBG and albumin were assayed in
morning blood samples obtained from 126 healthy men (aged 20-45 years) known to
have normal semen analysis. CFT concentrations calculated using four published
methods (i.e. the Sodergard, Nanjee-Wheeler, Vermeulen and Ly-Handelsman
equations) were compared with one another and the free androgen index. RESULTS:
Reference intervals for total testosterone and CFT by the Vermeulen equation were
9.4-31.0 nmol/L and 0.245-0.785 nmol/L (2.5-97.5 percentile), respectively. CFT
values varied considerably with the four equations examined. Mean biases ranged
from 5.8 to 56.0%; the Nanjee-Wheeler and Ly-Handelsman equations yielded
positive and negative biases, respectively, against the other equations. Free
androgen index was shown to correlate poorly with CFT (r2=0.21-0.46) and over
estimate the CFT at low SHBG concentrations. CONCLUSIONS: We have used various
equations to derive reference ranges for CFT in healthy men aged 20-45 years. We
suggest that CFT be incorporated into the investigation regimen for suspected
hypogonadism when total testosterone results are equivocal.
PMID- 17036416
TI - Media crucial to AIDS fight.
PMID- 17036417
TI - Routine, voluntary testing urged.
PMID- 17036419
TI - [Third-country physicians].
PMID- 17036418
TI - Radiculopathy and the herniated lumbar disc. Controversies regarding
pathophysiology and management.
PMID- 17036420
TI - [Oxytetral and Lindynette].
PMID- 17036421
TI - Valuing health.
PMID- 17036422
TI - Ethical clinical practice and sport psychology: when two worlds collide.
AB - From their own practices, the authors offer insight into potential ethical
dilemmas that may frequently develop in an applied psychology setting in which
sport psychology is also being practiced. Specific ethical situations offered for
the reader's consideration include confidentiality with coaches, administration,
parents, and athlete-clients; accountability in ethical billing practices and
accurate diagnosing; identification of ethical boundaries in nontraditional
practice settings (locker room, field, rink, etc.); and establishment of
professional competence as it relates to professional practice and marketing.
PMID- 17036423
TI - Medicare, the national quality infrastructure, and health disparities.
AB - What can Medicare do to improve quality and reduce disparities in clinical care?
Increasing the cultural competence of individual physicians and their use of
evidence-based guidelines will be useful--but insufficient. What is needed are
organized care management processes that will support physicians and medical
teams in their clinical decision-making, assist patients in managing their own
illnesses, and provide clinicians with feedback on their performance. Medicare
should therefore seek to strengthen both the capabilities of medical groups to
improve the quality of care and their incentives to do so. Unless carefully
designed, however, incentives to improve quality--such as pay for performance and
public reporting--could increase disparities, for example, by directing
additional resources to providers who are already performing at a high level.
Medicare should be alert to this possibility when devising incentives for quality
and should carefully study the effects of incentives on disparities. If general
efforts at quality improvement do not succeed in reducing disparities, targeted
measures will be required.
PMID- 17036424
TI - Ethical issues in exercise psychology.
AB - Exercise psychology encompasses the disciplines of psychiatry, clinical and
counseling psychology, health promotion, and the movement sciences. This emerging
field involves diverse mental health issues, theories, and general information
related to physical activity and exercise. Numerous research investigations
across the past 20 years have shown both physical and psychological benefits from
physical activity and exercise. Exercise psychology offers many opportunities for
growth while positively influencing the mental and physical health of
individuals, communities, and society. However, the exercise psychology
literature has not addressed ethical issues or dilemmas faced by mental health
professionals providing exercise psychology services. This initial discussion of
ethical issues in exercise psychology is an important step in continuing to move
the field forward. Specifically, this article will address the emergence of
exercise psychology and current health behaviors and offer an overview of ethics
and ethical issues, education/training and professional competency, cultural and
ethnic diversity, multiple-role relationships and conflicts of interest,
dependency issues, confidentiality and recording keeping, and advertisement and
self-promotion.
PMID- 17036425
TI - Re: New generation open-bite treatment with zygomatic anchorage. Angle Orthod.
2006; 76: 519-526.
PMID- 17036426
TI - Re: Failure rate of self ligating and edgewise brackets bonded with conventional
acid etching and a self etching primer: a prospective in vivo study. Angle
Orthod. 2006; 76: 119-122.
PMID- 17036427
TI - Improving Medicare's data on race and ethnicity.
AB - Medicare's databases provide a rich source of information about the program's 43
million beneficiaries. These data have played an important role in documenting
racial, ethnic, and socioeconomic disparities in health and health care. Because
they derive largely from administrative records that have been collected over
many years using varying standards, however, they are not fully adequate for
monitoring and reducing disparities. The Centers for Medicare & Medicaid Services
(CMS) has supported a number of initiatives to improve the quality of its data on
race and ethnicity. Yet analyses of 2002 Medicare administrative data show that
only 52 percent of Asian beneficiaries and 33 percent of both Hispanic and
American Indian/Alaska Native beneficiaries were identified correctly. As CMS
moves to reduce disparities, and as researchers strive to explain how and why
disparities occur, further improvements in Medicare's data are essential. Health
care organizations also need data on the race and ethnicity of the people they
serve in order to improve the quality of care for minorities. This brief provides
some recommendations for further efforts.
PMID- 17036428
TI - Health care need: three interpretations.
AB - The argument that scarce health care resources should be distributed so that
patients in 'need' are given priority for treatment is rarely contested. In this
paper, we argue that if need is to play a significant role in distributive
decisions it is crucial that what is meant by need can be precisely articulated.
Following a discussion of the general features of health care need, we propose
three principal interpretations of need, each of which focuses on separate
intuitions. Although this account may not be a completely exhaustive reflection
of what people mean when they refer to need, the three interpretations provide a
starting-point for further debate of what the concept means in its specific
application. We discuss combined interpretations, the meaning of grading needs,
and compare needs-based priority setting to social welfare maximisation.
PMID- 17036429
TI - Behavioural genetics: why eugenic selection is preferable to enhancement.
AB - Criminal behaviour is but one behavioural tendency for which a genetic influence
has been suggested. Whilst this research certainly raises difficult ethical
questions and is subject to scientific criticism, one recent research project
suggests that for some families, criminal tendency might be predicted by
genetics. In this paper, supposing this research is valid, we consider whether
intervening in the criminal tendency of future children is ethically justifiable.
We argue that, if avoidance of harm is a paramount consideration, such an
intervention is acceptable when genetic selection is employed instead of genetic
enhancement. Moreover, other moral problems in avoiding having children with a
tendency to criminal behaviour, such as the prospect of social discrimination,
can also be overcome.
PMID- 17036430
TI - A living will clause for supporters of animal experimentation.
AB - Many people assume that invasive research on animals is justified because of its
supposed benefits and because of the supposed mental inferiority of animals.
However probably most people would be unwilling to sign a living will which
consigns themselves to live biomedical experimentation if they ever, through
misfortune, end up with a mental capacity equivalent to a laboratory animal. The
benefits would be greater by far for medical science if living will signatories
were to be used, and also the mental superiority boast would no longer apply.
Ultimately, it is argued that invasive biomedical experiments would be
unacceptable in a democratic society whose members are philosophically self
consistent.
PMID- 17036431
TI - Is the argument from marginal cases obtuse?
AB - Elizabeth Anderson claims that the argument from marginal cases is 'the central
argument' behind the claim that nonhuman animals have rights. But she thinks,
along with Cora Diamond, that the argument is 'obtuse'. Two different meanings
could be intended here: that the argument from marginal cases is too blunt or
dull to dissect the reasons why it makes sense to say that nonhuman animals have
rights or that the argument from marginal cases is insensitive regarding
nonrational human beings (the marginal cases of humanity). The purpose of the
present article is to argue that, despite Anderson's and Diamond's nuanced and
perceptive treatments of the argument from marginal cases, this argument is not
obtuse in either sense of the term.
PMID- 17036432
TI - Protecting third parties in human subjects research.
PMID- 17036433
TI - General clinical research center staff nurse perceptions and behaviors regarding
informed consent: results of a national survey.
PMID- 17036434
TI - The problem with optimism in clinical trials.
PMID- 17036435
TI - Very early pregnancy.
PMID- 17036436
TI - Commentary on animal rights stirs more debate.
PMID- 17036437
TI - The informed consent process in a rural African setting: a case study of the
Kassena-Nankana district of Northern Ghana.
PMID- 17036438
TI - Protecting human subjects in the NIH's Intramural Research Program: a draft
instrument to evaluate convened meetings of its IRBs.
PMID- 17036439
TI - Caregivers as subjects of clinical drug trials: a review of human subjects
protection practices in published studies of Alzheimer's disease
pharmacotherapies.
PMID- 17036440
TI - Expressing freedom and taking liberties: the paradoxes of aberrant science.
AB - Complete freedom does not exist, despite people's preparedness to die for it.
Scientific freedom is much defended and yet much misunderstood. Scientists have
limits imposed on their freedom by the disciplines and discourse communities in
which they place themselves. Freedom within these socially constructed
constraints needs to be distinguished from taking liberties with the rules and
practices that make up these constraints, and validate the activities of special
groups within society. Scientists (and the public) perceive taking liberties with
science's rules and practices as aberrant science, and they often react
punitively. Aberrant science can be broadly examined under four headings: wicked
science, naughty science, dysfunctional science, and ideologically unacceptable
science. When we examine examples of perceived aberrant science, we find that
these categories of "misconduct" are connected and often confused. Scientific
freedom needs to be redefined with due regard to current understandings of
scientists as human beings facing powerful social pressures to deliver results of
a particular kind.
PMID- 17036441
TI - Prenatal diagnosis and selective abortion: a result of the cultural turn?
AB - There is a growing trend in obstetric medicine of prenatal diagnosis and the
selective abortion of foetuses that are likely to be born with a disability.
Reasons commonly given to explain this trend include the financial implications
of screening and testing policies, the disruption to families caused by the birth
of a child with a disability, and the potential quality of life of the unborn
child. This paper reflects upon another possible reason for this. It is argued
that it is, in part, a consequence of our attitudes towards disability and a
pursuit of aesthetic perfection. These attitudes arise from a social context that
may be explained by considering the effect on the disabled community of the
transition from modernity to postmodernity. This shift is demonstrated by
inspecting some of the synonymous developments in art history. It is suggested
that this "cultural turn" may have both helped and hindered people with
disabilities, but the hypothesis requires further testing. This could best be
achieved with a qualitative study of what motivates parental decision making in
the obstetric unit.
PMID- 17036442
TI - Medical ethics as therapy.
AB - In this paper, the author examines a style of teaching for a medical ethics
course designed for medical students in their clinical years, a style that some
believe conflicts with a commitment to analytic philosophy. The author discusses
(1) why some find a conflict, (2) why there really is no conflict, and (3) the
approach to medical ethics through narratives. The author will also argue that
basing medical ethics on the use of narratives has problems and dangers not fully
discussed in the literature.
PMID- 17036443
TI - Intellectual property and biotechnology: the U.S. internal experience--Part II.
AB - Continuing the discussion begun in the March 2006 issue of the Kennedy Institute
of Ethics Journal, this paper further documents the failure of the United States
to adequately consider possible modifications in the traditional robust system of
intellectual property rights as applied to biotechnology. It discusses concrete
suggestions for alternative disclosure requirements, for exemptions for research
tools, and for improved access to clinical advances. In each of these cases, the
modifications might be more responsive to the full set of relevant values.
PMID- 17036444
TI - Academic freedom and academic-industry relationships in biotechnology.
AB - Commercial academic-industry relationships (AIRs) are widespread in biotechnology
and have resulted in a wide array of restrictions on academic research.
Objections to such restrictions have centered on the charge that they violate
academic freedom. I argue that these objections are almost invariably
unsuccessful. On a consequentialist understanding of the value of academic
freedom, they rely on unfounded empirical claims about the overall effects that
AIRs have on academic research. And on a rights-based understanding of the value
of academic freedom, they rely on excessively lavish assumptions about the kinds
of activities that academic freedom protects.
PMID- 17036445
TI - The ethical limits in expanding living donor transplantation.
AB - The past decade has witnessed the emergence of novel methods to increase the
number of living donors. Although such programs are not likely to yield high
volumes of organs, some transplant centers have gone to great lengths to
establish one or more of them. I discuss some of the ethical and policy issues
raised by five such programs: (1) living-paired and cascade exchanges; (2)
unbalanced living-paired exchanges; (3) list-paired exchanges; (4) nondirected
donors; and (5) nondirected donors catalyzing cascade exchanges. I argue that
living-paired and cascade exchanges are ethically sound, but will lead to only a
few additional transplants. Unbalanced exchanges and list-paired exchanges raise
ethical issues that should limit their permissibility. Nondirected donations can
be ethically sound with adherence to strict eligibility criteria and fair
allocation procedures. Nondirected donors catalyzing cascade exchanges can be
ethically sound provided that individuals with blood types O and B are not made
worse off.
PMID- 17036446
TI - Multiple roles and successes in public bioethics: a response to the public forum
critique of bioethics commissions.
AB - National bioethics commissions have been critiqued for a variety of structural,
procedural, and political aspects of their work. A more recent critique published
by Dzur and Levin uses political philosophy to constructively critique the work
of national bioethics commissions as public deliberative forums. However, this
public forum critique of bioethics commissions ignores empirical research in
political science and normative claims that suggest that advisory commissions can
and should have diverse of functions beyond that of being public forums. The
present paper argues that the public forum critique too narrowly considers the
roles that bioethics commissions can play in public bioethics and ignores the
moral obligation of commissions to fulfill their mandates. Evaluations of
commissions must consider that these institutions can serve in capacities other
than those of a public deliberative forum and use additional measures to evaluate
the multiple roles and successes of bioethics commissions in public policy.
PMID- 17036447
TI - Quality use of medicines and nurses.
PMID- 17036448
TI - Topic: current issues and challenges in community health.
PMID- 17036449
TI - The caregiving experience: how much do health professionals understand?
AB - Legal, social and economic factors have changed the delivery of care to people
who have a mental disorder. Many of these people are now treated in the community
and they live with or in close proximity to their family. The aim of this paper
is to provide health professionals with an insight into the experience of being a
caregiver to a person with a person with a mental disorder. For these families
caregiving becomes an integral part of everyday life. Positive outcomes for both
the caregiver and the ill family member are more likely to occur when effective
levels of collaboration exist between health professionals and caregivers.
Collaboration is enhanced when caregivers and health professionals value each
other's contribution to the ill family member's care. Often the burden, stress,
and socio-economic effects on the family caring for a person with mental illness
is not sufficiently appreciated and further increases this burden. A review of
the literature from the caregiver's perception is presented. An increased
understanding of the caregiving experience will enable health professionals to
develop and implement strategies that facilitate positive outcomes for the
caregiver and the ill family member.
PMID- 17036450
TI - The trials and tribulations of team-nursing.
AB - AIM: The aim of this study was to review the team-nursing approach to care
adopted by two general medical wards in a large private hospital. The delivery
model of care was reviewed to determine the factors that enhance and/or hinder
the timely delivery, continuity and communication of care. METHOD: All nursing
and ancillary staff who worked on two medical wards at a private teaching
hospital were invited to participate in the study. Thirty eight participants from
the two wards took part in focus group discussions, individual interviews and
completed the Staff Continuity of Care Questionnaire. FINDINGS: Findings
indicated that achieving functionally sound teamwork is a complex task that is
affected by the interplay of a number of organisational, patient and staff
factors. Its smooth application is further affected by the uncertain and changing
conditions on the wards, which are difficult to control and impact on the smooth
delivery of patient care. The findings revealed strengths and weaknesses in
teamwork, communication of care, documentation and discharge planning. The
results also highlighted factors that enhance and hinder the smooth delivery of
care. This paper details the factors that influence the delivery of care from the
perspectives of nursing staff and makes recommendations to enhance the delivery
of patient care using a team-nursing approach.
PMID- 17036451
TI - Occupational health nursing practice in Australia: what occupational health
nurses say they do and what they actually do.
AB - This study investigated current activities of occupational health nurses (OHN) in
Australia related to the applicability of and their involvement in emergent role,
wellness-based practices and traditional role and illness-based practices. A
questionnaire encompassing the eight Areas of Practice as articulated by the
Australian College of Occupational Health Nursing (ACOHN) competency standards
was used to obtain data from 93 OHNs affiliated with ACOHN. More traditional role
Areas of Practice such as treatment services, health assessment and
rehabilitation services were seen as more applicable to their practice and a
substantial amount of time was spent on them. Managing occupational health and
safety (OH&S) service' was the only emergent area that was a substantial part of
the OHN's role. Less time was devoted to other emergent and pro-active areas of
OHN practice, such as illness and injury prevention, health promotion, health
education and research into OH&S. While less time was allocated to emergent Areas
of Practice, and they were ranked more lowly they were considered to be
applicable to practice. The findings of this study suggest that OHNs in Australia
may not be engaging fully in all Areas of Practice that have been articulated by
the ACOHN, particularly emergent role activities. Although Australian OHNs
perform all the activities articulated in the ACOHN Areas of Practice, their
focus is still primarily illness and injury based, and also management. While the
profession is supportive of emergent role activities, there is a need to debate
possibilities, undertake research into barriers and supports for emergent role
activities, more clearly articulate future directions for the OHN role, and
develop strategies to support OHNs as they develop their professional role.
PMID- 17036452
TI - A longitudinal study of student and experienced nurses' self-concept.
AB - Researchers continue to emphasise the importance of professional identity or
nurses' self-concept in the retention debate, although limited research has been
undertaken on this specific issue. The purpose of this study was to capitalise
upon recent advances in self-concept theory and measurement to identify, compare,
and contrast the development of self-concept for graduate and experienced nurses.
The Self Description Questionnaire III was used to assess four areas of general
self-concept and a newly developed Nurses Self-Concept Questionnaire was used to
assess six domains of self-concept specific to nursing. Student nurses completed
instrumentation during their final year of a University course (N=506) and 6
months after graduation (N=110). Experienced nurses completed instrumentation at
the end of the year (N=528) and eight months later (N=332). The results revealed
that graduate self-concept was lower than experienced nurse self-concept in most
domains at initial measurement (Time 1). Whilst some graduate self-concept
domains demonstrated a rise in mean scores at eight months (Time 2), scores
remained significantly lower overall than those of experienced nurses. The domain
of Nurse General Self-Concept had fallen significantly from the student to
graduate experience. Little change in the self-concept domains occurred over time
for the experienced nurse group. The results provide valuable empirical evidence
elucidating the development of nurses' self-concept. Key implications include the
need to monitor self-concept development in graduate nurses and develop
strategies for self-concept enhancement particularly for new graduates' Nurse
General Self-Concept.
PMID- 17036453
TI - Mentoring matters: developing rural nurses knowledge and skills.
AB - Mentoring, the alliance of two people with varying degrees of experience in order
to create opportunities for support and learning, is being encouraged as a
response to current workforce issues in Australian rural nursing. The nursing
profession is beginning to recognise the benefits of mentorship in providing
psychosocial support and role acquisition skills to novice practitioners. These
outcomes are valuable for enhancing the recruitment and retention of staff. The
Mentor Development and Support Project of The Association for Australian Rural
Nurses (AARN), established in 2003, was a strategy for increasing mentoring in
the rural nursing workforce. This project aimed to develop the capacity of rural
nurses to mentor effectively, as well as provide support for them for the
duration of the mentoring partnership. This article reports on aspects of the
AARN project. It includes a discussion of the need for planned mentor development
opportunities and provides the rationale for the curriculum content of project
workshops. It also includes evaluated outcomes for participants in the project.
PMID- 17036454
TI - Continuing the dialogue: a reply to Bernard Gert.
AB - Continuing the dialogue begun in the March 2006 issue of the Kennedy Institute of
Ethics Journal, I suggest that Bernard Gert's response to my paper does not
adequately address the criticisms I make of his theory's application to bioethics
cases.
PMID- 17036455
TI - [The problems of diagnostics, treatment and prevention arrangement in patients of
therapeutic profile].
AB - The recent data research from many countries demonstrates that severe and
sometime irreversible complications as a result of inadequate manipulations of
physicians affect hundreds of thousands of people. The defects of treatment are
more obvious in surgery than in therapy. To qualify the manipulations of the
therapist as proper or non-proper is much more difficult as compared with
erroneous conclusion in diagnostics. Underestimation and belated resolution of
this issue is fraught with the most grave consequences.
PMID- 17036456
TI - [Cost availability and patient satisfaction of hospital care].
AB - The results of sociological questionnaire of 1496 patients of oblast and region
hospitals related to cost availability and patient satisfaction of hospital care.
About 75% of respondents considered their treatment spendings as significant. It
is established that degree of patients' satisfaction of hospital care depends on
length of stay at the in-patient department. The longer it is the fewer patients
satisfied with medical care are. It is proposed to organize in hospitals among
socially unprotected patients evaluation of individual spendings for medical care
to protect constitutional rights of the population and to reveal factual cost of
medical care in the framework of the territorial program of public guarantees.
PMID- 17036457
TI - [The analysis of morbidity of child population according municipal polyclinics
data].
PMID- 17036458
TI - [The quality of life of patients with oncological gynecological pathology during
period of involution].
AB - The representative group of women older than 40 years with oncological
gynecological pathology during involution period was examined. Quality of life of
these patients and their attitude to their health as well was studied during
various rehabilitation periods of the course of this disease. Survey was applied
using questionnaire MOS-SF 36 Health Survey 2.0 with subsequent statistical data
processing. The results can be applied to enhance effectiveness of preventive
activities in gynecology and practical and research medicine.
PMID- 17036459
TI - [The study of the possibility of development and diagnostics of kidney diseases].
PMID- 17036460
TI - [Diseases of musculo-skeletal system in railway personnel].
AB - Epidemiological and medical-social aspects of diseases of locomotor system and
conjunctive tissue in railway personnel (1993-2004) are analyzed. The established
negative trends in propagation of diseases locomotor system predetermine priority
of preventive measures in organization of medical care for the patients of this
category. Establishment of medical rooms for preventing diseases of locomotor
system is recommended.
PMID- 17036461
TI - [The physical conditions of seventeen-year-old adolescents in Omskaya Oblast].
AB - In Omskaya Oblast, among seventeen-year-old adolescents 70.5% of males and 58.5%
of females are of sufficient degree of average, above average and higher physical
state. Study of integrated impact of various factors on physical state deviations
established that 33.9% of these factors belong to the medical category. This fact
emphasizes higher significance of quality of applied diagnostic and therapeutic
and preventive actions. Marked impact was also provided by living conditions
(17.8%), education conditions (17.7%), family life-style (16.1%), natural
climatic conditions and degree of anthropogenic pollution of environment (14.5%).
Most of these factors are controllable enough to provide reserve for grading of
lower degree of adolescents' physical state.
PMID- 17036462
TI - [The medical personnel of hospice as object of study of professional activity
impact on personality].
AB - Data of questionnaire survey of clinical specialists providing medical care to
oncological patients at IV stage of prevalent malignant neoplasms is discussed.
Impact of professional activities on development of professional-personal
desadaptation (burnout) in medical personnel is presented. Survey results permit
to determine the approaches to psychological care and psychological monitoring of
personnel activities in medical institutions of oncological services.
PMID- 17036464
TI - [The system of dataware in quality management of medical care rendering in
Samarskaya oblast].
PMID- 17036463
TI - [The actual issues of ambulance medical care in the the Russian Federation].
AB - Issues of organization of ambulance medical care to the population of the Russian
Federation are discussed.
PMID- 17036465
TI - [Marketing activities of sanatorium resort institutions].
PMID- 17036466
TI - [The actual problems of organization of medical care for rural population].
AB - Population health status and medical care in rural areas is discussed. Trends in
dynamics of such health indicators as mortality, morbidity and prevalence of
socially perilous diseases are worse among rural population as compared with
urban population. Economical, environmental, industrial and other factors
impacting on health of rural population are revealed. Sociological research data
demonstrating attitude of rural population to health and to medical care are
quoted. Problems of financing, manpower strength and material and technical
equipping in rural health institutions are discussed. Importance of priority
national project "Health" for enhancement of rural medical care is shown
including necessary measures for its realization.
PMID- 17036467
TI - [The role of special programs of HIV/AIDS prevention].
PMID- 17036468
TI - [The characteristics of main resources of oncological institutions of Far East of
the Russian Federation].
PMID- 17036469
TI - [The conditions and ways enhancing stomatological care of rural population].
PMID- 17036470
TI - [Dynamics and regional characteristics of medical demographic indicators in the
Republic of Kazakstan].
PMID- 17036471
TI - [The teaching of pathology in faculty of medicine of Moscow University in XVIII
century].
PMID- 17036472
TI - [The sanitary organization of cities of Russia in the late XIX--early XX
centuries].
PMID- 17036473
TI - [From the history of Zemstvo pharmacy (according materials from Kurskaya
province)].
PMID- 17036474
TI - [Clinical observation on catgut implantation at acupoint for treatment of general
paroxysmal epilepsy].
AB - OBJECTIVE: To search for an effective method for treatment of general paroxysmal
epilepsy. METHODS: One hundred cases were randomly divided into a treatment group
of 50 cases treated with catgut implantation at Dazhui (GV 14), Jinsuo (GV 8),
Fenglong (ST 40), etc., and a control group of 50 cases treated with oral
administration of sodium valproate. RESULTS: The scores for epilepsy after
treatment significantly improved in the both groups (P<0.05); the total effective
rate was 94.0% in the treatment group and 82.0% in the control group with a
significant difference between the two groups (P<0.05). CONCLUSION: Catgut
implantation at acupoint has a definite therapeutic effect on general paroxysmal
epilepsy with no adverse effect.
PMID- 17036475
TI - [Observation on treatment of chronic pelvic inflammatory with point injection
combined with ultra-laser radiation].
AB - OBJECTIVE: To probe into clinical therapeutic effect of point injection combined
with ultra-laser radiation on chronic pelvic inflammatory. METHODS: Sixty cases
of chronic pelvic inflammatory were divided into a treatment group and a control
group, 30 cases in each group. The treatment group were treated with point
injection of Yuxingcao Injectio combined with ultra-laser point radiation, and
the control group with simple point injection of Yuxingcao Injectio, once each
day, for 4 weeks. RESULTS: Twenty-eight cases were effective with a total
effective rate of 93.3% in the treatment group, and 23 cases were effective with
a total effective rate of 76.7%; the weighty pain of lower abdomen, abnormal
leucorrhea and signs of gynecological examination, etc. in the treatment group
significantly improved as compared with the control group (P<0.05). CONCLUSION:
Point injection combined with ultra-laser radiation has definite therapeutic
effect on chronic pelvic inflammatory.
PMID- 17036476
TI - [Clinical observation on therapeutic effect of electroacupuncture at Sanyinjiao
(SP 6) on peri-menopausal syndrome].
AB - OBJECTIVE: To objectively evaluate the effectiveness and safety of
electroacupuncture (EA) at Sanyinjiao (SP 6) for treatment of peri-menopausal
syndrome. METHODS: All the patients enrolled were randomly divided into a
treatment group and a control group. The treatment group were treated with EA at
Sanyinjiao (SP 6) for 3 therapeutic courses, thrice each week, 30 min each time,
one month constituting one course. The control group were treated with oral
administration of nylestriol for 3 months, 2 mg each time, twice each month. For
the menopausal patient, medroxyprogesterone was added from the third month of the
treatment for 7 days, 6 mg each day. Changes of vasomotorial symptoms, mental
symptoms and scores of Kupperman indexes before and after treatment for 1 month,
2 months and 3 months were investigated. RESULTS: EA could significantly decrease
the score of Kupperman indexes, improve vasomotorial symptoms and mental symptoms
in the patient of peri-menopausal syndrome with no severe adverse effects. The
control group in the score of Kupperman indexes was slightly higher than the
treatment group with no significant difference between the two groups, but the
treatment group in improvement of the vasomotorial symptoms was better than the
control group and in improvement of mental symptoms was not as good as the
control group. CONCLUSION: EA at Sanyinjiao (SP 6) is effective and safe for
treatment of peri-menopausal syndrome.
PMID- 17036477
TI - [Randomized controlled study on ginger-salt-partitioned moxibustion at shenque
(CV 8) on urination disorders poststroke].
AB - OBJECTIVE: To probe the therapeutic effect and safety of ginger-salt-partitioned
moxibustion on urination disorders poststroke. METHODS: Eighty-two cases of
cerebral apoplexy, including cerebral infarction and cerebral hemorrhage, with
urination disorders induced by neurogenic bladder at restoration stage were
randomly divided into a treatment group treated with ginger-salt-partitioned
moxibustion at Shenque (CV 8) and routine acupuncture, and a control group
treated with routine acupuncture. Thirty-nine cases in the treatment group and 36
cases in the control group completed all treatments. The treatment was given 5
times each week and the therapeutic effects were observed after treatment of 3
consecutive weeks. RESULTS: Ginger-salt-partitioned moxibustion in improvement of
mean urination times of each day, mean times to be asked to awaken for the
nursing personnel at night, mean times of urgent urinary incontinence at day for
the patient, cases-times of urinary incontinence of the patient at night, and
increasing degree of urinary incontinence was better than the control group
(P<0.01, P<0.05). CONCLUSION: Ginger-salt-partitioned moxibustion is a safe and
effective therapy for urination disorders poststroke.
PMID- 17036479
TI - [Clinical observation on acupuncture for treatment of central obesity].
AB - OBJECTIVE: To observe and evaluate objective therapeutic effect of acupuncture on
central obesity. METHODS: Thirty-two cases of central obesity were treated with
body acupuncture combined with electroacupuncture, ear point tapping, TDP
radiation, and changes of WC, WHR and body mass index (BMI) before and after
treatment were observed. RESULTS: The clinical total effective rate was 84.4%,
and WC, WHR and BMI decreased (P<0.001). CONCLUSION: Acupuncture combined with
electroacupuncture, ear point tapping, TDP radiation has a better therapeutic
effect on central obesity.
PMID- 17036478
TI - [Effects of injection of Huangqi injectio into Zusanli (ST 36) on immune function
in the patient of schizophrenia].
AB - OBJECTIVE: To study on effects of injection of Huangqi Injectio into Zusanli (ST
36) on the hospital infection and immune function in the patient of
schizophrenia. METHODS: Thirty inpatients of chronic schizophrenia were treated
with injection of Huangqi Injectio into bilateral Zusanli (ST 36), 2 mL each
point, thrice each week, for 8 weeks. Relative immune indexes and the hospital
infection were investigated. RESULTS: The hospital infection and the sub
infection were 4 cases (13.3%), 7 cases-times (23.3%) in the injection group; and
9 cases (15.0%), 19 cases-times (31.7%) in the control group, respectively, with
no significant difference between the two groups (P>0.05). The drug
administration duration was 7.77 days/case and 11.87 days/case in the two groups,
respectively (P<0.01). In the injection group, as compared with that of last 3
years the duration was 7.77 days/case and 14.08 days/case (P<0.01). IgG, IgA, IgM
and T-cell subgroups did not have significant changes, but there was the most
different value before and after injection in SIL-2R of the no-infection group,
and the longer the drug administration duration, the smaller the different
values. CONCLUSION: Injection of Huangqi Injectio into Zusanli (ST 36) has
definite effect for prevention of the hospital infection in inpatients of chronic
schizophrenia, and SIL-2R is a valuable index for investigation of the hospital
of infection.
PMID- 17036480
TI - [Application of acupuncture in imaging of changing pyloric antrum and duodenal
bulb metamorphosis].
AB - OBJECTIVE: To probe into the effect of acupuncture in imaging diagnosis on
changing pyloric antrum and duodenal bulb metamorphosis, and provide reliable
evidence for confirming pathological characters. METHODS: Among 30 cases needing
image examination, 18 cases had metamorphosis of duodenal bulb and 12 cases had
metamorphosis of pyloric antrum. Acupuncture was given at Zusanli (ST 36) with
uniform reinforcing-reducing method, and with moderate-strong stimulation. The
needle was retained for 2 min. After pressing point Zhongwan (CV 12), changes of
image were investigated. RESULTS: After acupuncture, the metamorphosis alleviated
in 26 cases, with an effective rate of 86.7%. CONCLUSION: This method is simple,
convenient and objective with no adverse effects.
PMID- 17036481
TI - [Study on the needling depth of point Yaotu with CT scanning].
AB - OBJECTIVE: To probe the safe depth and angle of needling the point Yaotu for
treatment of prolapse of intervertebral disc. METHODS: CT technique was used for
scanning investigation of the depth and angle of needling the point Yaotu.
RESULTS: When the acupuncture needle was inserted vertically to the external
space of intervertebral foramen of human body with arrival of qi, the tip of
needle could reach to 73 mm deep, which is the best needling depth and angle.
CONCLUSION: The needle vertically inserting to the external space of
intervertebral foramen at the point Yaotu is proper in treatment of prolapse of
intervertebral disc.
PMID- 17036482
TI - [Re-cognition of the Jinglin theory in the Internal Classic].
AB - OBJECTIVE: To summarize the Jijgiin theory and study the essence of Jingjin.
METHODS: Analyze the meaning of the word, anatomical basis, symptoms and
treatment of Jingjin. CONCLUSION: The Jingjin theory in the Internal Classic is
formed on the basis of 12 division method of the surface, reflecting internal
relations among the skeletal muscles and the crux of injury, and summarizing
treatment methods of Jingjin diseases; and the meaning of essence of the Jingjin
is nerve and muscles.
PMID- 17036483
TI - [Study on vascular morphology of integument tissues of the channel area in the
leg].
AB - OBJECTIVE: To observe the distribution of the blood vessels in the integument
tissue of the channel area of legs. METHODS: The integument tissue of the lower
limbs in the 12 cadavers were dissected with macro-and micro-dissection,
radiographical technique of systemic artery and technique of image pattern
analysis to observe and analyze the origins, branches and anastomoses in the
integument tissues along the channels of legs. RESULTS: The distributional
density of the blood vessels in the integument tissues of legs along the channel
area of the three-yin meridians of the foot, the Gallbladder Meridian, and the
Urinary Bladder Meridian was higher than that in the other parts. They formed an
obvious nutrient vascular chain on the arteriogram. The distributional density in
the channel area of the Stomach Meridian was not obviously increased and the
obvious nutrient vascular chain could not be seen. CONCLUSION: An obvious
nutrient vascular chain is formed in the integument tissue along the channel area
of legs except the Stomach Meridian.
PMID- 17036484
TI - [Effects of different acupuncture intensities on the therapeutic effect and the
gastric electric activity in the patient of diabetic gastroparesis].
AB - OBJECTIVE: To observe clinical therapeutic effect of different acupuncture
intensities on diabetic gastroparesis and to search for the best acupuncture
intensity for treatment of diabetic gastroparesis. METHODS: Eighty cases were
randomly divided into 4 groups, strong, moderate, weak acupuncture intensity
groups and an oral hypoglycemic drug group, 20 cases in each group. Two weeks of
treatment constituted one course. RESULTS: The total effective rates were 85.0%,
95.0%, 85.0% in the acupuncture groups, respectivelly, with significant
difference as compared with 65.0% of the control group (P<0.05). The moderate
intensity acupuncture group had the best clinical therapeutic effect. The
principal frequency and amplitude of the stomach electrogastrogram in the gastric
antrum and the stomach body significantly improved in the acupuncture groups,
which was better than those in the control group (P<0.05). CONCLUSION:
Acupuncture has significant therapeutic effect on diabetic gastroparesis, and
there is a dose-effect relation between different intensities of acupuncture and
curative effects,which are correlated with the regulation of the gastric electric
parameters.
PMID- 17036485
TI - [Comparison of therapeutic effects between normal acupuncture and shallow
needling with short-needle on periarthritis of shoulder].
AB - OBJECTIVE: To compare therapeutic effects between normal acupuncture and shallow
needling with short-needle, and search for therapeutic tool and method easy to be
accepted by the patient of periarthritis of shoulder. METHODS: One hundred and
fifty-two cases of periarthritis of shoulder were randomly divided into 2 groups.
They were treated by normal acupuncture and shallow needling with short-needle,
respectively. The two groups were same in acupoints selected and the therapeutic
course, and their therapeutic effects and the accepting degrees of the patient
were investigated. RESULTS: The cured rate was 67.1% in the normal acupuncture
group and 69.7% in the shallow needling with short-needle group, with no
significant difference between the two groups (P>0.05). CONCLUSION: Normal
acupuncture and shallow needling with short-needle have similar therapeutic
effect on periarthritis of shoulder, but the shallow needling with short-needle
can obviously relieve the pain and mental fear in treatment, easy to be accepted.
PMID- 17036486
TI - [Effects of acupuncture on expressions of transcription factors NF-E2, YB-1,
LRG47 in the SAMP10 mouse].
AB - OBJECTIVE: To explore the mechanism of acupuncture in delaying aging. METHODS:
Using SAMP10 mice and normal control SAMR1 as model and applying RT-PCR and DIG
probed Northern blot techniques to observe expression of NF-E2, YB-1, LRG47 genes
in whole brain, cortex and hippocampus in the 8-month SAMR1 control group, 8
month SAMP10 control group, 8-month SAMP10 acupuncture group and 8-month SAMP10
non-point acupuncture group. RESULTS: In the SAMP10 control group, the expression
of NF-E2, YB-1 and LRG47 were down-regulated in the whole brain, cortex and
hippocampus, and after acupuncture they were up-regulated and tended to normal.
CONCLUSION: Aging of the SAMP10 mouse brain is related with expression of NF-E2,
YB-1 and LRG47 genes, and acupuncture can regulate the expression of NF-E2, YB-1
and LRG47 genes, improving the functions of erythrocyte series, increasing
proliferation of cells and immune function of cells in anti-bacteria, hence anti
aging.
PMID- 17036487
TI - [Effects of electroacupuncture on behaviors and dopaminergic neurons in the rat
of Parkinson's disease].
AB - OBJECTIVE: To explore the possibility of electroacupuncture (EA) for prevention
of the injury of dopaminergic neurons in the substantia nigra of the rat with
Parkinson's disease. METHODS: Wistar rats were randomly divided into a normal
group, a model group, a sham-operation group and an EA group. 6-OH-DA was
injected into right substantia nigra of the midbrain to made Parkinson's disease
rat model with single side substantia nigra injury, and TH/TUNEL method and
rotation behavior observation method were used to observe changes of rotation
behavior and apoptosis of dopaminergic neurons in the substantia nigra after EA
at "Taichong" (LR 3) and "Fengfu" (GV 16) for 3 d, 7 d and 14 d. RESULTS: The
rotation times/min were same at 3 d, 7 d and 14 d were the basically same in the
model group, and at 14 d significantly decreased in the EA group (P<0.05); the
rotation starting time at 7 d and 14 d in the model group were significantly
longer than those in the EA group (P<0.05); the rotation lasting time at 3 d, 7 d
and 14 d in the model group and the EA group were gradually shortened (P<0.01, or
P<0.05), but at 7 d, 14 d in the model group were significantly longer than those
in the EA group (P<0.05); the DA neuron apoptosis number in the model group were
significantly higher than those in the normal group, with a very significant
difference (P<0.01); the apoptosis number in the EA group tended to decrease, at
7 d and 14 d were significantly lower than that in the model group (P<0.05).
CONCLUSION: Electroacupuncture can effectively prevent from injury of
dopaminergic neurons in the substantia nigra of the rat with Parkinson's disease.
PMID- 17036488
TI - [Observation on therapeutic effect of scalp acupuncture analgesia on labor].
AB - OBJECTIVE: To observe analgesic effect of scalp acupuncture on labor. METHODS:
Seventy primiparae with term pregnancy and monocyesis were randomly divided into
scalp acupuncture group treated by acupuncture at the Shengzhi area of scalp, and
control group by no treatment. Pain grades before and after scalp acupuncture
were evaluated with the pain 4-grade rating criteria stipulated by WHO, and the
active stage and the second birth process, the Apgar scores of new-born and
postpartum hemorrage amount were compared between the two groups. RESULTS: The
labor pain with 1 to approximately 2 grades was found in 33 cases in the scalp
acupuncture group, and 2 cases in the control group with very significant
difference between the two groups (P < 0.01); the active stage was (130.70 +/-
74.16 ) min and the second birth process was (40.70 +/- 21.65) min in the scalp
acupuncture group, and (166.15 +/- 62.65) min and (53.30 +/- 26.93) min in the
control group, respectively, with significant differences between the two groups
(all P < 0.05); and there were no significant differences in Apgar score of new
born and postpartum hemorrhage amount. CONCLUSION: Scalp acupuncture has a better
analgesic effect in vaginal delivery with no adverse effect on the mother and
infant.
PMID- 17036489
TI - [Prof. WU Lian-zhong's 12 acupuncture analgesic methods].
AB - Prof. WU Lian-zhong not only has great theoretical attainments and rich clinical
experience, but also is good at summarization and study, especially,
systematically and deep study on various kinds of pain from etiology,
pathogenesis, characteristics, classification and syndrome differentiation,
treatment method and point selection and other aspects, and sums up the 12
treatment methods such as regulating mental activities, removing obstruction in
the channels, opposing needling, blood-letting puncture, sixteen cleft points,
warming the channels, resistant needling, Su needling, surrounding needling,
tripod needling, penetration needling and dragon-tiger contending method, which
are of very important significance for guiding clinical acupuncture analgesia.
PMID- 17036490
TI - [Brief discusion on importance of accurate location in acupuncture treatment for
periarthritis of shoulder].
AB - Briefly discuss some recognation problems about acupuncture treatment of
periarthritis of shoulder at present and put forward the methods for diagnosis
and acupuncture treatment based on accurate location.
PMID- 17036491
TI - [A new thinking of acupuncture and moxibustion treatment of shoulder pain after
hemiplegia].
AB - Analysis from anatomy and physiology indicates that causes of shoulder pain are
(1) decline and after-constriction of the scapula;(2) the adduction and intorsion
of the humerus; (3) the spasm of the upper limb flexor. The acupuncture and
moxibustion prescriptions stipulated for prevention and treatment of shoulder
pain are Jianjing (GB 21), Jianzhongshu (SI 15), Jugu (LI 16), Tianzong (SI 11),
Jianliao (SJ 14), Jiquan (HT 1) at the flaccid hemiplegia, and Jugu (LI 16),
Jianyu (LI 15), Tianzong (SI 11), Jianliao (SJ 14), Xiaoluo (SJ 12), Shanglian
(LI 9), Wenliu (LI 7) at the spastic hemiplegia , in combination with cupping at
the Urinary Bladder Meridian on the back and around shoulder. Thus, it is
indicated that shoulder pain not only is involved in the shoulder joint but also
in all muscle groups of the shoulder girdle and the upper limb extensor at the
affected side.
PMID- 17036492
TI - [Exploration and reflection on bilingual teaching of acupuncture and
moxibustion].
AB - OBJECTIVE: To explore bilingual teaching of acupuncture and moxibustion for
cultivating compound senior acupuncture persons. METHODS: Beginning with the
concept of bilingual teaching in conjunction with acupuncture own
characteristics, the problems involved in the practice of bilingual teaching of
acupuncture and moxibustion were analyzed and explored. RESULTS: Unifying opinion
and correct localizing position should be started for acupuncture and moxibustion
bilingual teaching, and choice of teachers, subjects, models, materials,
examination of bilingual teaching should be focused on, and appropriate means
should be applied in practice to test, consolidate and distillate the effect of
bilingual teaching. CONCLUSION: Bilingual teaching of acupuncture and moxibustion
is an important measure of economic globalization and knowledge economy. Only if
various teaches involved in its practice were properly dealt with could better
teaching results be obtained.
PMID- 17036493
TI - [Jingluo, Jingmai and their English translation].
AB - Chinese meaning and English translation of Jing, Luo, Mai, Jingluo, Jingmai and
other terminology of Chinese medicine are compared from both writing and medical
theory, raising that the Jingmai in the Internal Classic should include both the
channel system and the vessel system. From the form of the characters or
functions and structures, the Jing is longitude and the Luo is net, Mai is
vessels, and the concept and function of Jingluo (channels and collaterals) and
Jingmai (the meridians and vessels) do not allow obscure. In ancient times, Jing
and Mai were jointly called as Jingmai, aimed at understanding network state of
the channels and collateral system through tangible distribution of the vesselar
system. Translation of "Jing mai" as the meridians and collaterals or channels
and collaterals practically is only translated a half of real meaning of Jingmai.
PMID- 17036494
TI - [Survey of point prescriptions of acupuncture treatment for urinary retention].
AB - OBJECTIVE: To summarize characteristics of the point prescriptions for
acupuncture treatment of urinary retention from 1994 to 2005. METHODS: Review of
literature was made from following five aspects: body acupuncture, scalp
acupuncture, ear acupuncture, hand acupuncture and abdomen acupuncture. For the
prescriptions of body acupuncture, further analysis was made on single point
prescription, distal-proximal point association, superior-inferior point
association, point selection according to syndrome differentiation and point
selection according to disease differentiation. CONCLUSION: Acupuncture has
affirmative therapeutic effect on urinary retention. However, there are still
problems to be resolved in clinical researches at present.
PMID- 17036495
TI - [On key role of acupoints in elongated needle therapy].
AB - OBJECTIVE: To study on characteristics and application of key acupoints in
Elongated Needle Therapy. METHODS: Probe into method of determining key acupoints
and their clinical application from characteristics of channels, characteristics
of acupoints, position of diseases, pathogenesis, syndromes and other aspects.
CONCLUSION: Establishment of the theory of key acupoints of enlongated needle
therapy reflects the principle of "fewer but better" in acupoint selection of
enlongated needle therapy, which can reduce pain of the patient and increase the
therapeutic
PMID- 17036496
TI - [The role of inflammation in the pathogenesis of late diabetic complications].
AB - Chronic inflammation plays an important role in the development of diabetes and
its late complications. Over nutrition, physical inactivity, stress, truncal
obesity, dyslipidaemia, hypertension and smoking directly and indirectly activate
the family of nuclear factor kappa B, the principal factor of inflammatory
response. Hiperglycaemia and especially brittle diabetes affect not only
metabolic abnormalities but also modulate cell and humoral immune response. There
is good evidence that looking for novel risk factors for development and
progression of late diabetic complications among inflammatory markers are needed.
Progress in the study on etiopathogenesis of micro- and macro-angiopathy have
clinical implications.
PMID- 17036497
TI - [Implantation of cardiac pacemaker in children, author's experiences].
AB - Cardiac pacemaker was implanted as a therapeutic method for children with atrio
ventricular block, sick sinus syndrome, LQT syndrome, cardio-depressive syncope.
Twenty six children (aged 1-17) underwent pacemaker implantation or exchange of
pacemaker and electrode. In nineteen cases cardiac peacemaker was implanted in
the endocardial system; in the next seven cases epicardial system was required.
The difference between the implantations depended on patient's age and the
character of the disease. The single chamber peacemaker was implanted in twenty
children, dual-chamber in six patients. There were no visible complications in
follow up observation and constant heart stimulation can be considered as a safe
way of children's severe bradycardia treatment.
PMID- 17036498
TI - [Serum cytokine concentration as prognostic factor in patients with alcoholic
liver disease].
AB - AIM OF THE STUDY: Estimation if the serum concentration of cytokines: IL-2, IL-4,
IL-6, IL-8, IL-10, TNF-alfa and CRP can be useful in the assessment of prognosis
in patients with alcoholic hepatitis (ALH) and alcoholic liver cirrhosis (ALC).
Attempt to find their correlation with clinical stage and life prognosis in all
patients. MATERIALS AND METHODS: We examined 24 patients with alcoholic liver
disease, hospitalised in Department of Gastroenterology: 13 male and 11 female at
the age 26-72 years. According to clinical symptoms and laboratory tests in 15 of
them alcoholic hepatitis (in 9 confirmed by liver biopsy) and in 9 - liver
cirrhosis (2 confirmed by liver biopsy) were diagnosed. The interview, physical
examination, abdominal ultrasound, biochemical tests and viral tests were
performed in all patients. We excluded patients treated with steroids and
cytostatics. Serum concentration of cytokines and CRP were established three
times during the first week of hospitalisation. RESULTS AND CONCLUSIONS: In all
patients IL-2 and IL-4 concentration were in a range characteristic for healthy
people. There was statistically important correlation between the severe clinical
stage and high concentration of serum IL-6 (p<0.000319), IL-8 (p<0.000708), TNF
alfa (p<0.000018) and CRP (p< 0.001611) in patients with ALC. High concentration
of serum IL-6, IL-8, TNF-alfa and CRP were correlated with poor prognosis (3
patients with ALC and the highest concentration died). High concentration of IL
6, IL-8, TNF-alfa and CRP were correlated with heavy clinical stage and poor
prognosis so their evaluation can be helpful in the assessment of prognosis in
patients with ALC and ALH.
PMID- 17036499
TI - [Clinical image of oral mucous membrane in rheumatoid arthritis patients].
AB - The aim of the study was to evaluate the character and frequency of pathological
changes in the oral cavity mucous membrane and xerostomy in patients with
prolonged hospital and ambulatory treatment due to rheumatoid arthritis (RA).
EXAMINATION MATERIAL: The study was conducted in 120 patients with RA, average
age 54, and in the control group of 40 generally healthy examinees, average age
53. RESULTS: In patients with RA pathological changes in the oral cavity appeared
much more frequently: erosions, fissures, perleche, candidiasis oris, lichen
Wilsoni, leukoplakia and persistent xerostomy. RA patients more often used
partial prosthesis and more frequently were edentulous. CONCLUSIONS: The
treatment of oral cavity diseases and prophylaxis should be provided together
with the RA treatment, with special emphasis put on the elimination of xerostomy.
Good cooperation of rheumatologists and periodontologists is recommended RA
diagnosis.
PMID- 17036500
TI - [Candida infections of the oral mucosa--not only a dental problem].
AB - Frequency of occurrence of mycotic infections of the oral mucosa is higher in
later years. It is connected with common use of antibiotics, intensive cancer
treatment (cytostatics, radiation therapy) as well as immunosuppressant drugs and
antibiotics, which have an influence on mikroflora disorders of the oral cavity.
Candidiasis of oral mucosa occurs in old patients, in people suffering from
diabetes mellitus, hypothyreosis, sideropenia, hypovitaminosis and xerostomia,
which is often caused by hypofunction of salivary glands during autoimmune
diseases and/or drug and systemic treatment. The aim of the study was to make a
retrospective evaluation of frequency of occurring mycotic infections in patients
treated in the Department of Periodontology and Oral Mucosa Diseases, Medical
University of Gdansk in the 2003, as well as recognition of systemic conditioning
of these disorders. The Study material was clinical documentation of 4172
patients, treated because of different oral mucose and periodontium disorders.
From these patients, selected was a group of 105 (83 women and 22 men) with
diagnosis--Candidosis mucosae oris. Clinical and mycotic examination was
performed. RESULTS: Mycotic infections were found in 105 patients (2.5%).
Systemic diseases (74.3%) were found in a maturity of the patients, which
indicated systemic predispositions to candida infections. CONCLUSION: A wide
cooperation between general practitioners and dentists, especially perio
dontologists, is necessary to give full care to patients. Early diagnosis of
disorders of the oral cavity of patients with systemic diseases and dentistry
treatment or taking preventive measures seems to be necessary.
PMID- 17036501
TI - [Completed suicide in outline--on basis of Cracow's Institute of Forensic
Medicine data in 1991-2000 years].
AB - The study presents the results of research into completed suicide. The authors
have analyzed cases of completed suicide committed in Cracow and it's environs in
the years 1991-2000. The aim of the research is to describe some features of this
phenomenon with it's transformations in the last periods. The presented material
bases on archival data of postmortem examinations made in Cracow's Institute of
Forensic Medicine. Analyses' were executed in reference of victims' sex, age and
place of residence, number and frequency of suicides in Cracow population,
methods, predictors and possible motives. The authors also present a sketch of
the bibliography regarding the topic, and the comparison between the results of
the present study and the results of earlier studies from Cracow environs of the
phenomenon of suicide. 1933 cases of completed suicides were analysed, from what
over a half concerned occupants of our city. The average coefficient for 100 000
occupants carried out 13.2. There were 1485 men and 448 women among victims, in
age from 13 to 95 years. Male to female avarage ratio carried out 3.3:1 in the
described period.. Average age carried out 45.5 years, for men 44.5, and for
women 48.8 years. The superiority of men is strongly visible in groups of young
persons and in "middle age". Results from archival data show that, hanging was
the the most frequent way of suicide. In studied material there were more then
63% cases of suicidal hanging. Falls from height, poisonings and drownings were
next in line. In very considerable number of cases (almost 60%) the presence of
mental disorder in anamnesis was affirmed. This concerned particularly women
where the most frequent were depression disorders. For men, first of all factors
was dependence from acohol. Over one third of the victims were pensioners and
unemployeds. The level of ethanol in blood in 718 cases was crossed 0.5 promille.
PMID- 17036502
TI - [Concentration and activity of cathepsin D in the blood plasma and serum of
patients with abdominal aortic aneurysm].
AB - Concentration and activity of cathepsin D are markedly higher in the blood plasma
of patients with abdominal aortic aneurysm than in the blood plasma of healthy
subjects. The difference results from release of big amounts of procathepsin D
and increased release of the active enzyme into circulating blood of patients
with aortic aneurysm. Concentration and activity of cathepsin D in the blood
serum of patients with aortic aneurysm are also higher than in the serum of
healthy subjects. Concentration and activity of cathepsin D are markedly higher
in the blood serum of patients with aortic aneurysm and in healthy subjects as
compared to the blood plasma. The difference is due to the release of marked
amounts of procathepsin D and cathepsin D from morphotic elements in vitro during
blood coagulation and clot retraction.
PMID- 17036503
TI - [Incidence, pathogenesis and importance of nocturnal hypoxaemia in patients with
chronic obstructive pulmonary disease].
AB - Noctural hypoxaemia (NH) in patients with chronic obstructive pulmonary disease
(COPD) was first described over 40 years ago, however, its importance is not
fully established. NH is defined most frequently as a drop in oxygen saturation
below 90% and it occurs in almost all COPD patients PaO2 < 55 mmHg and in 30-40%
of those with PaO2 < 60 mmHg. The main reason for NH is alveolar hypoventilation
which is most pronounced during ohase REM. It is known that even short term
episodes of NH increase pulmonary artery pressure, yet, the impact of chronic,
isolated NH on pulmonary hypertension development was not found. Also, the
relationship of induced by NH cardiac arrythmias with sudden death in COPD was
not documented and association of NH with prognosis in COPD was not proved.
Actually, there is no need to perform NH examination routinely. According to the
ATS/ERS latest standards, the determination of NH can be helpful to qualify COPD
patients with PaO2 55-65 mmHg to longterm oxygen therapy.
PMID- 17036504
TI - [Clinical implication of ischemic preconditioning in protection of reperfused
tissues].
AB - Ischemic preconditioning (IP), has emerged as a powerful experimental method of
ameliorating ischemic-reperfusion injury in a variety of organs. Clinical trials
using IP have been successfully carried out. They support the existence of IP
induced cyto-protection in humans as well. IP induced "ischemia tolerance" and
"reperfusion tolerance" mechanisms are presented. The new, recently discovered
modifications of IP "remote preconditioning" and "postconditioning" and their
possible clinical applications in the ischemia of human: heart, liver, lung,
brain, kidney and skeletal muscles are discussed.
PMID- 17036505
TI - [Difficulties in differential diagnosis of Sjogren's syndrome and systemic lupus
erythematosus].
AB - Sjogren's Syndrome (SS) is the second most common autoimmune disorder after
rheumatoid arthritis (RA). It can be found as a lone condition (primary Sjogren's
Syndrome) or may accompany other autoimmune rheumatic diseases (secondary
Sjogren's Syndrome). Despite such frequent occurrence, accurate diagnosis of
Sjogren Syndrome is difficult. These difficulties result from highly variable
symptoms of SS as well as from common presence of other autoimmune disorders. In
the following article authors present current knowledge concerning clinical
symptoms, diagnostic methods and latest clinical guidelines on the diagnosis of
SS. Differential diagnosis of SS and systemic lupus erythematosus (SLE) is also
discussed.
PMID- 17036506
TI - [The evolution of insulin therapy and new insight into nutrition recommendations
for individuals with diabetes].
AB - The dietary guideline has undergone change during the last decades. It has been
done by the introduction of new insulin therapy methods, also by the numerous
epidemiological studies which have documented the influence of eating habits on
macro-vascular diseases, obesity and type 2 diabetes. The Glycemic Index (GI) and
Glycemic Load (GL) play a pivotal role in carbohydrate classification and for
food choice by diabetic patients. Post-prandial glycemia response and insulinemia
strongly relate to value of GI and GL. Intensive insulin therapy as a multiple
daily injection or pump therapy has brought a liberalization in diabetic regime
and diet. It gives possibility to introduce modern dietary guidelines including
healthy eating advice with respect for traditional eating habits.
PMID- 17036507
TI - [The role of glycemic index concept in carbohydrate metabolism].
AB - Glycemic index (GI) is a system of classifying carbohydrate-containing foods
according to how fast they are digested and absorbed during the postprandial
period. It is a measure of the quality of carbohydrates based on their direct
effect on blood glucose levels during 2 hours after the meal. As a reference
point--glucose is used, with GI equal 100. A related concept, glycemic load (GL),
take into consideration also amount of carbohydrates in portion of food. GL is
calculated by multiplying the GI by the amount of available carbohydrates (g) and
dividing total by 100. GI's value can be affected by a number of factors,
including the variety and ripeness of food or method of processing, cooking and
storage. GI of particular product, as well as mixed meal is modulated by other
food components like fat, protein, organic acids, dietary fiber and also
antynutrients. In general, low GI foods include most fruits and vegetables, beans
and legumes, and whole grain products. Refined grain products and potatoes have a
high GI. The GI has proven to be a more useful nutritional tool than is the
traditional classification of carbohydrates (as simple or complex, as sugars or
starches, or as available or unavailable), permitting new insights into the
relation between the physiologic effects of carbohydrate-rich foods and health.
Several prospective observational studies have shown that the chronic consumption
of a diet with a high glycemic load is independently associated with an increased
risk of obesity, developing type 2 diabetes, cardiovascular disease, and certain
cancers.
PMID- 17036508
TI - [Education of the patient for therapy with personal insulin pump].
AB - Insulin pump therapy is a diabetes management tool that can significantly aid in
achieving treatment goals in children, adolescents and adults with type 1
diabetes mellitus. These goals include optimal glycaemic control, lifestyle
flexibility, quality-of-life improvement, and independence. Successful
implementation of CSII requires a motivated, conscientious patient with a range
of technical skills and self-management capabilities. Patients develop this
knowledge through the program of education provided by a healthcare team
including diabetologists, diabetes educator, dietietian, pump manufacturer
representative, and in some cases, mental health professionals. Training of the
patient to use a pump includes three basic steps: 1 - pre-pump education, 2 -
pump start-up, 3 - evaluation, independence assessment and re-education. It is a
relatively long process that can range from a few weeks to several months.
Insulin pump therapy checklist, included in this paper, is a useful tool in
planning and providing education for insulin pump users.
PMID- 17036509
TI - [The role of transforming growth factor-beta in the pathogenesis of diabetic
retinopathy].
AB - Diabetic retinopathy is a micro-angiopathy affecting predominantly small vessels
of the retina. Proliferative diabetic retinopathy is characterised by preretinal
neovascularisation and fibrosis leading to vitreous heamorrhage and tractional
retinal detachment. Chronic hyperglicemia may cause growth factor alterations
that are likely to participate in tissue remodeling typical for this late
complication. Numerous angiogenic and mitogenic factors have been demonstrated to
be present in the eye, including transforming growth factor-beta (TGF-beta),
insulin-like growth factors, fibroblast growth factor, tumor necrosis factor and
vascular endothelial growth factor. TGF-beta is involved in the control of
endothelial cell proliferation, adhesion and deposition of extracellular matrix,
thus TGF-beta may play a role in the control of endothelial cell proliferation
seen in the disease. The role of TGF-beta in diabetic retinopathy enables better
understanding, and thus in the future better intensive antidiabetic therapy in
aspect of ophthalmic complications.
PMID- 17036510
TI - [Procedures in treatment of hemorrhoids].
AB - Current conceptsof ethiopathogenesis and classification of hemorrhoids are
presented based on the literature and own experience of the authors. Different
surgical and non-surgical methods are discussed with additional description of
postoperative treatment and complications.
PMID- 17036511
TI - [Recurrent crural phlegmonous abscesses as a sign of Munchausen syndrome in a
young woman].
AB - We present a case of a 22-year-old woman chronically treated in many hospitals
because of recurrent crural phlegmonous abscesses. Several months' follow up
revealed Munchausen syndrome--a rare psychiatric disorder--manifesting with self
perpetuated and repeated fabrication of illness resulting in wandering from
hospital to hospital for diagnosis and treatment. The above patient produced the
abscesses by deliberately traumatizing her skin. The case points to Munchausen
syndrome as a possible rare cause of some long, unsuccessfully treated diseases.
PMID- 17036512
TI - [Giant hydronephrosis of the upper left kidney in the case of complete, one-sided
double pelvis].
AB - We present the case of giant hydronephrosis in double pelvis of the left kidney.
Patient was admitted to the urology department with hypertension and palpable
giant mass in the abdomen. During imaging examination (CT, MRI ) the diagnosis of
double pelvis and ureter on left side was established. The upper collecting
system was extremely hydronephrotic and afunctional. Patient underwent partial
nephrectomy - upper part of left kidney. We evacuated 9 liters of stagnated
urine. After surgery blood pressure normalised, renal efficiency remained normal.
PMID- 17036513
TI - [Rudolf Arend (1898-1980)--The forgotten first director of the Cracovian
Neurology Clinic of the Medical Academy in the year 1950].
PMID- 17036514
TI - Lung cancer mortality patterns in women resident in different urbanization areas
in central Italy from 1987-2002.
AB - AIMS AND BACKGROUND: The aim of the study was to evaluate mortality lung cancer
trends, as an indicator of female smoking trends, in women resident in different
urbanization areas. METHODS AND STUDY DESIGN: Data on the 5782 female lung cancer
deaths that occurred in Tuscany, Italy, during the period 1987-2002 were
analyzed, using age-period-cohort models by areas at different urbanization
levels. Trends were examined with a log-linear regression model, calculating the
yearly estimated percent change. Empirical bayesian estimators of the ratios
between observed and expected deaths by municipality were calculated for the most
recent period and mapped. RESULTS: The age-adjusted lung cancer mortality rates
increased from 1987 to 2002: estimated percentage change values were equal to
24.5% in the urban areas (P < 0.001) and 17.2% in the rural areas (P = 0.023).
The age-period-cohort model analyses showed a statistically significant drift and
non-linear cohort effects. The higher risk was observed for the birth cohort of
women born around 1955 (RR, 5.25; 95% CI, 2.83-9.72). In the rural areas, no
significant effects were observed, and the age model showed the best fit. In
recent years, the risk appeared concentrated in 9 Tuscan municipalities,
accounting more than 35% of the female urban population. CONCLUSIONS: The
observed significant cohort effect in the age-period-cohort analyses for the
urban areas reflects the social impact of living in these areas to induce smoking
related disease like lung cancer in women. The risk appeared particularly
relevant in more recent and urbanized generations (women born around 1955),
thereby suggesting urgent effective campaigns against smoking, gender dedicated,
especially in urban areas.
PMID- 17036515
TI - Quality control of the autopap screening system employed as a primary screening
device: rapid review of smears coded as no further review.
AB - AIMS AND BACKGROUND: Automated reading of smears is increasingly used in cervical
screening, and quality control procedures to check its performance are required.
The aim of the present study was to evaluate the usefulness of rapid review of
all smears coded as "no further review" (NFR) by the AutoPap system as a quality
control procedure. METHODS: From 2002-2005, 153,269 smears were processed by
AutoPap at the Centro per lo Studio e la Prevenzione Oncologica of Florence,
Italy, and 24,503 (15.9%) were coded as NFR. All NFR smears underwent immediate
rapid review by expert readers. RESULTS: Sixty-five of 118 NFR cases reviewed as
ASCUS-R complied to recommended 6 months cytology, and 25 of 30 NFR cases
reviewed as ASCUS-SIL or more severe accepted immediate colposcopy. As a result
of such assessment, one single case of microinvasive carcinoma was detected in a
woman aged 34 years: NFR smear had been reviewed as AGCUS, was followed by repeat
AGCUS cytology and repeat negative colposcopy, and finally underwent conization.
CONCLUSIONS: NFR report at AutoPap was associated with an extremely high negative
predictive value, which might suggest using AutoPap as a primary screening tool,
with NFR report prompting a "return to screening" recommendation. Rapid review of
NFR smears is not recommended as a quality control measure for the negligible
yield of high-grade lesions detected.
PMID- 17036516
TI - Clinical presentation and treatment of gastrointestinal stromal tumors.
AB - AIMS AND BACKGROUND: Gastrointestinal stromal tumors (GISTs), although rare, are
the most common mesenchymal neoplasms affecting the gastrointestinal tract. We
present our experience in the treatment of localized and metastatic disease and a
review of literature. PATIENTS AND METHODS: Nine patients were observed from
April 2002 to July 2004. Eight tumors were in the gastric area and 1 was in the
small bowel. In 5 cases, complete surgical removal was performed, and none of
these patients underwent adjuvant therapy. The remaining 4 cases, with locally
advanced or recurrent disease, were treated with imatinib. RESULTS: The patients
with localized disease treated only by surgery did not relapse. In the patients
with locally advanced or metastatic disease treated by imatinib, we observed 3
partial responses, and one case was not assessable because he had no measurable
disease. In 2 of 3 responders, it was possible to perform a new radical surgery.
CONCLUSIONS: Our series is too small to draw any conclusion. According to our
review of the literature, surgery remains the standard treatment for non
metastatic GISTs. Imatinib mesylate represents a major breakthrough in the
treatment of advanced GISTs and is the first effective systemic therapy for the
disease.
PMID- 17036517
TI - Chemotherapy with mitomycin C and capecitabine in patients with advanced
colorectal cancer pretreated with irinotecan and oxaliplatin.
AB - AIMS AND BACKGROUND: To assess the activity and tolerability of the combination
of mitomycin C and capecitabine in patients with metastatic colorectal cancer
after failure of irinotecan and oxaliplatin-containing regimens. METHODS: We
retrospectively reviewed 28 patients with pretreated advanced colorectal cancer
who had been treated with mitomycin C, 6 mg/m2 on day 1, and capecitabine, 1900
mg/m2 on days 1-14, every 3 weeks. Tumor assessment was performed every 3 cycles,
toxicity assessed at each cycle. RESULTS: Main patient characteristics were
median age, 61 years (range, 35-73); male/female ratio, 16/12; single metastatic
site involvement, 5/28 (18%); > or =3 metastatic sites, 10/28 (36%). Ninety-six
courses of therapy were given (median number, 3; range, 1-9). Twenty-six patients
were assessable for response, and all were assessable for toxicity. There was 1
partial response (4%) and 12 had stable disease (43%). Median time to progression
was 2 months (range, 1-9) and median overall survival was 6 months (range, 1
29+), with a 1-year overall survival rate of 25%. The regimen was very well
tolerated without significant hematological toxicity. CONCLUSIONS: Our results
are disappointing. Despite the good safety profile, they do not support further
investigation or the routine use of this regimen in this setting.
PMID- 17036518
TI - Single-agent irinotecan as second-line weekly chemotherapy in elderly patients
with advanced colorectal cancer.
AB - AIMS AND BACKGROUND: Irinotecan is a standard option for relapsed/refractory
advanced colorectal cancer. Although in a recently reported, randomized trial it
was found that a regimen of irinotecan once every 3 weeks was associated with a
lower incidence of severe diarrhea than with weekly treatment with similar
efficacy, there is no evidence in the literature that suggests the optimal dosing
strategy for the drug, along with treatment efficacy and safety, following 5
fluorouracil/oxaliplatin-based chemotherapy in elderly patients. A phase II study
has reported significantly reduced toxicity when irinotecan was administered once
a week for 2 weeks, followed by a week rest. PATIENTS AND METHODS: From January
2004 to April 2005, we analyzed, retrospectively, our data on single-agent
irinotecan as a second-line chemotherapy in elderly patients (> or =70 years)
with advanced colorectal cancer. Twenty-three patients were evaluated. CPT-11 (80
mg/m2) was given as a 60-min intravenous infusion in repeated 21-day courses
comprising weekly treatment for 2 consecutive weeks followed by a 1-week rest.
Tumor measurements were obtained after every third course of therapy. Toxicity
was assessed weekly using the National Cancer Institute Common Toxicity Criteria,
version 2. RESULTS: The median number of treatment courses received per patient
was 4 (range, 1-8). All patients were assessable for toxicity and 21 for
response. The most frequently observed severe toxicities were diarrhea (grade 3,
13%) and neutropenia (grade 3, 30.4%; grade 4, 8.6%). Only 1 case of neutropenic
fever occurred. Other hematological and non-hematological toxicities were mild
and manageable. Objective partial responses were observed in 3 patients (13%). An
additional 10 patients (43%) had stable disease as their best response. To date,
12 patients have progressed with a median time-to-progression of 4.3 months and a
median survival of 8.3 months. CONCLUSIONS: A weekly irinotecan administration
can induce tumor control in elderly patients with advanced colorectal cancer that
has progressed during or shortly after 5-fluorouracil/oxaliplatin-based
chemotherapy. However, a careful monitoring of hematological toxicity and special
instructions to prevent and manage diarrhea are mandatory in this setting of
patients.
PMID- 17036519
TI - Is radiation a risk factor for atherosclerosis? An echo-color Doppler study on
Hodgkin and non-Hodgkin patients.
AB - AIMS AND BACKGROUND: The aim of the present paper was to study the role of
irradiation in the atherosclerotic process in patients affected by Hodgkin and
non-Hodgkin lymphoma. METHODS: We studied 84 subjects, 42 with Hodgkin or non
Hodgkin disease and 42 controls. All 42 cases had been irradiated and were
comparable in terms of risk factors for atherosclerosis. All 84 subjects
underwent echo-color Doppler of the arterial axis (carotids, abdominal aorta, and
femoral arteries), and the intima-media thickness was measured. RESULTS: The
irradiated cases had a greater intima-media thickness in the carotid district,
even after dividing them according to age and sex; males were affected more than
females. The irradiated patients were at greater risk of developing
cardiovascular events than the controls. CONCLUSIONS: An echo-color Doppler of
the carotid district is advisable in all patients who have been submitted to
radiotherapy, and the patients with a significantly greater than normal intima
media thickness need a strict follow-up, and antioxidant or antiaggregant therapy
should be considered.
PMID- 17036520
TI - Temozolomide and radiotherapy as first-line treatment of high-grade gliomas.
AB - AIMS AND BACKGROUND: Temozolomide, a novel alkylating agent, has shown promising
results in the treatment of patients with high-grade gliomas, when used as single
agent as well as in combination with radiation therapy. MATERIALS AND METHODS: In
this report we retrospectively reviewed the clinical outcome of 128 consecutive
patients with a diagnosis of high-grade gliomas referred to our Institutions from
April 1994 to November 2001. The first 64 patients were treated with radiotherapy
alone and the other 64 with a combination of radiotherapy and temozolomide (31
with radiotherapy and adjuvant temozolomide and 33 with radiotherapy and
concomitant temozolomide followed by adjuvant temozolomide). RESULTS: Grade 3
hematological toxicity was scored in 9% of 64 patients treated with radiotherapy
and temozolomide. No grade 4 hematological toxicity was reported, and the other
acute side effects observed were mild or easily controlled with medications. Age,
histology and administration of temozolomide were statistically significant
prognostic factors associated with better 2-year overall survival. In contrast,
we did not observe a significant difference in overall survival between adjuvant
and concomitant/adjuvant temozolomide administration. CONCLUSIONS: We report the
favorable results of a schedule combining radiotherapy and temozolomide in the
treatment of patients with high-grade gliomas. The literature data and above all
the findings of the phase III EORTC-NCIC 26981 trial suggest that actually the
schedule can be used routinely in clinical practice. Further clinical studies,
using temozolomide in combination with other agents, are required.
PMID- 17036521
TI - Assistance to parents who have lost their child with cancer.
AB - AIMS AND BACKGROUND: To assess the psychological needs of parents after the death
of their child from cancer. METHODS: The study comprises a preliminary
retrospective phase to identify parents who spontaneously contacted the medical
staff, followed by a prospective phase in which families were contacted by
telephone and were invited to a meeting. RESULTS: The retrospective study
demonstrated that more than 50% of the families spontaneously sought contact with
the department. In the prospective study, 17 families were contacted and the
majority of them subsequently decided to come to the department for a talk.
CONCLUSIONS: Our experience shows that parents have a strong need to have further
contact with the team that took care of their children for months. In the process
of coping with bereavement, anxiety and depression are common and not necessarily
pathological, though there may be psychopathological reactions that can interfere
with the parents' quality of life.
PMID- 17036522
TI - c-erbB-2 protein level in tissue and sera of breast cancer patients: a possibly
useful clinical correlation.
AB - AIMS AND BACKGROUND: The aims of this study were to assess the clinical utility
of circulating preoperative HER-2 extracellular domain p105 detected by enzyme
immunoassay (ELISA), to compare the tissue expression of HER-2/neu determined by
immunohistochemistry (IHC), to correlate prognostic factors including tumor size,
nodal involvement, and hormone receptor status, and to analyze the prognostic
significance of the marker in relation to clinical outcome as measured by disease
free and overall survival. METHODS: In this study, we enrolled 108 consecutive
patients with breast carcinoma, and obtained serum samples and frozen tumor
tissues. We compared them with 57 women with fibroadenoma and 63 healthy women as
controls. RESULTS: Univariate ANOVA analysis showed no relationship between HER
2/neu in tissue and serum. Preoperative serum levels of p105 were significantly
higher in breast cancer patients than in women with benign disease or healthy
women. Concerning the correlation between p105, HER-2/neu tissue expression, and
the other prognostic factors, a statistically significant correlation between
high serum p105 levels and ER-negative status in breast cancer patients was
found. Kaplan-Meier analysis confirmed that patients with positive HER-2/neu
tissue expression had a significantly shorter survival than those with negative
expression. Analysis with the Cox model demonstrated that tumor size was the only
significant independent prognostic factor. CONCLUSIONS: This research failed to
demonstrate a relationship between preoperative tissue overexpression and
circulating HER-2/neu, suggesting that p105 does not represent a valid
alternative to predict a worsened prognosis in breast cancer, but it could be a
diagnostic marker to discriminate healthy subjects from breast cancer patients.
PMID- 17036523
TI - Urinary neopterin in patients with liver tumors.
AB - AIMS AND BACKGROUND: Primary and secondary liver tumors are associated with poor
prognosis. Neopterin is an indicator of systemic immune activation, and increased
neopterin concentrations have been associated with poor prognosis in a wide range
of malignant tumors. METHODS: Urinary neopterin was determined by high
performance liquid chromatography in 154 patients with primary and secondary
liver tumors. The survival of different groups of patients was compared by log
rank test, and Cox regression was used for multivariate analysis. RESULTS:
Urinary neopterin was significantly increased in patients compared to controls. A
statistically significant correlation was observed between urinary neopterin and
age of the patients, hemoglobin concentration, mean erythrocyte volume and
peripheral blood leukocyte or platelet count. In univariate analysis, urinary
neopterin below 214 micromol/mol creatinine, peripheral blood leukocytes below 8
x 10(9)/L, hemoglobin equal to or above 125 g/L, no extrahepatic tumor, stage of
liver involvement, and colorectal, breast or ovarian primary were significant
prognostic factors for survival. In multivariate analysis, Bengtsson stage,
presence of extrahepatic involvement, primary other than colorectal, breast or
ovarian carcinoma, peripheral blood leukocyte count and urinary neopterin were
independent prognostic factors. Increased urinary neopterin during and at the end
of follow-up was also associated with poor prognosis. CONCLUSIONS: Urinary
neopterin is increased in patients with liver tumors. Neopterin is an independent
prognostic indicator in patients with liver tumors along with Bengtsson stage,
presence of extrahepatic disease, primary site and peripheral blood leukocyte
count.
PMID- 17036524
TI - The correlation between TTF-1 immunoreactivity and the occurrence of lymph node
metastases in patients with lung cancer.
AB - AIMS AND BACKGROUND: Thyroid transcription factor (TTF-1) is a tissue-specific
transcription factor expressed in the epithelial cells of thyroid and lung. The
aim of this study was to evaluate the relationship between the expression of TTF
1 and clinico-pathological parameters in pulmonary adenocarcinoma and
adenosquamous carcinoma. METHODS: Resection material of pneumonectomies and
lobectomies of 39 patients was retrospectively examined. Twenty-eight patients
were diagnosed with adenocarcinoma and 11 with adenosquamous carcinoma. Tumors
were classified into 3 groups: a strongly positive group (++) with double dagger
50% tumor cells positive for TTF-1; a weakly positive group (+) with 1-49%
positive tumor cells; and a negative group (-) with less than 1% or no positive
tumor cells. Analysis was performed with Kaplan-Meier estimates and log-rank
tests. RESULTS: Staining for TTF-1 was negative in 10 cases. There was focal
staining in 9 cases, while there was diffuse staining in 20 (51%) cases out of
39, and 15 (75%) of these were adenocarcinomas. There was a statistically
significant association between TTF-1 and lymph node metastases (P = 0.029). No
relationship was found between TTF-1 positivity and disease-free and overall
survival. CONCLUSIONS: TTF-1 expression may be a predictor of lymph node
metastases. Additional work in a larger group of patients is needed to better
assess the utility of this marker.
PMID- 17036525
TI - Combining independent studies of diagnostic fluorodeoxyglucose positron-emission
tomography and computed tomography in mediastinal lymph node staging for non
small cell lung cancer.
AB - AIMS AND BACKGROUND: A meta-analysis of diagnostic test performance was conducted
to compare the results of relevant studies reporting diagnostic accuracy values
for mediastinal staging in patients with non-small cell lung cancer (NSCLC). This
paper deals with the two most accurate imaging techniques currently in use:
positron emission tomography (PET) with FDG and computed tomography (CT). A
statistical pooling method was used to perform a quantitative meta-analysis aimed
at demonstrating the potential advantage of one of these two methods. METHODS:
Studies in all languages published between 1998 and 2005 that examined the use of
FDG-PET and CT for mediastinal staging in NSCLC patients, enrolled at least 18
participants, and provided enough data to allow calculation of sensitivity and
specificity rates were considered eligible for the quantitative meta-analysis.
Statistical methods to pool the overall estimates of sensitivity and specificity
and to compare the discriminant power of PET and CT were discussed and used.
RESULTS: Of the 13 studies included in the analysis, 12 reported greater accuracy
of FDG-PET than CT in detecting mediastinal lymph node metastases. The
sensitivity of FDG-PET ranged from 50% to 100%. The estimate of the overall
sensitivity was 0.83% with 95% CI (0.749-0.913). Specificity ranged from 79% to
100%, with an overall estimated specificity of 0.87% with 95% CI (0.80-0.95). For
CT, the sensitivity and specificity ranged from 50% to 97% and 58% to 94%,
respectively; the overall estimate was 0.68% with 95% CI (0.582-0.788) and 0.76%
with 95% CI (0.668-0.859). The summary receiver operating characteristic (SROC)
approach was used to assess the superior diagnostic accuracy of one of the two
methods. The areas under the two SROC curves were AUC(PET) = 0.909 vs. AUC(CT) =
0.794. CONCLUSIONS: Numerical and visual results of the meta-analysis of recent
relevant reports agreed that FDG-PET is more accurate than CT in identifying
mediastinal lymph node metastases in non-small cell lung cancer.
PMID- 17036526
TI - Self-expanding metal stents in gastrointestinal interventional radiology:
technical problems.
AB - AIMS AND BACKGROUND: To analyze the procedural difficulties in the placement of
metal stents in stenoses of the digestive tract and optimize the technique.
METHODS: Twenty-nine patients with digestive tract stenoses were treated from
January 1999 to December 2004. In 14 cases the stricture was anastomotic (9
colorectal, 3 esophageal, 1 gastroesophageal and 1 gastrojejunal), in 13
esophageal, in 1 gastric and in 1 duodenal. The stenosis was due to scarring in 5
patients and was malignant in 24 patients (primary in 17 cases and secondary in 7
cases). RESULTS: The procedure achieved technical success in all cases but 2. For
each of the different segments the technical difficulties and the adopted
procedural solutions were analyzed. CONCLUSIONS: The interventional radiology
approach yielded results comparable to those reported for the endoscopic method
and was always well tolerated. The need to rely on materials mostly designed for
endoscopic use can make radiological use difficult in some cases.
PMID- 17036527
TI - Phyllodes tumor with osteosarcomatous differentiation: a comparative
immunohistochemical study between epithelial and mesenchymal cells.
AB - AIMS AND BACKGROUND: Phyllodes tumor of the breast with osteosarcomatous
differentiation is rare and very little is known about its molecular profile.
METHODS AND STUDY DESIGN: An immunohistochemical panel with 37 primary antibodies
including cytokeratins, mesenchymal markers, key regulators of the cell cycle,
oncogenes, apoptosis-related proteins, metalloproteinases and their inhibitors
was performed on a formalin-fixed paraffin-embedded sample of phyllodes tumor
with osteosarcomatous differentiation in a 49-year-old woman. RESULTS:
Antiapoptotic stimuli (survivin) predominated in sarcomatous cells.
Antiproteolytic stimuli (TIMP-1, TIMP-2 and PAI) were preponderant in all cells,
a surprising fact in view of the aggressiveness of the neoplasm. The
immunoprofile of the osteoblastic and stromal cells was quite similar, except for
c-erbB-3, c-myc, cyclin D1 and p21. Both exhibited positive cells for actin,
MyoD1 and GFAP. CONCLUSIONS: Our results suggest that this osteosarcoma may have
originated from metaplasia of stromal cells that underwent a malignant change.
PMID- 17036528
TI - Cystic hygroma of the breast: a rare lesion.
AB - Lymphangiomas are congenital malformations of lymphatic vessels. More than 50% of
these lesions are present at birth; 90% are diagnosed by the age of 2. These
lesions do not expand very rapidly but they tend to infiltrate surrounding
tissues; their degeneration into malignant tumors is an extremely rare
occurrence. They are mostly located in the neck region and the axilla; breast
lymphangioma is very rare. Surgery is usually performed for aesthetic reasons and
in order to make a differential diagnosis with other, more common lesions. The
surgical procedure involves the excision of the mass; other methods, such as
radiotherapy and sclerotherapy, have proved to be completely ineffective.
PMID- 17036529
TI - Metastasis of giant cell tumor to the breast: case report and review of the
literature.
AB - Breast cancer is the most common type of malignancy in women. Of all breast
cancers, 0.5-3% involve metastasis of a non-breast malignancy to the breast.
Metastasis of soft tissue tumors to the breast is rarely seen. In particular,
metastasis of a giant cell tumor to the breast has never been reported in the
literature. We present here a case of breast metastasis in a 44-year-old woman
with a diagnosis of malignant giant cell tumor originating from the distal radius
and metastatic to the lung, who had been treated with radiotherapy, surgery and
chemotherapy.
PMID- 17036530
TI - Acute liver failure as the initial manifestation of hepatic infiltration by a
solid tumor: report of 5 cases and review of the literature.
AB - BACKGROUND: Acute liver failure is a rare complication of metastatic liver
disease with a high mortality. Recognition of malignant infiltration of the liver
as the cause of acute liver failure could be a diagnostic challenge. PATIENTS:
The medical files of 5 patients with acute liver failure due to metastatic liver
disease collected over a 4-year period (1997-2000) in our department were
reviewed. RESULTS: No patient had a past history of cancer. The interval from
jaundice to encephalopathy ranged from 7 to 12 days (median, 10). Physical
examination revealed hepatomegaly and deep jaundice in all patients. AST
elevation ranged from 147 to 1870 IU/L (median, 716 IU/L) and ALT elevation from
74 to 556 IU/L (median, 138 IU/L). All patients died within 4-14 days (median, 7)
of admission. None had papillary edema or decerebrate posture before death. Four
patients had concurrent renal impairment. Liver imaging studies in 2 of the 5
patients were nondiagnostic and the malignant liver infiltration was confirmed
postmortem. Liver histology in all cases showed massive tumoral infiltration of
the hepatic sinusoids with diffuse replacement of hepatocytes. The primary tumors
were colon, gastric, small cell lung, pancreas and cancer of unknown origin.
CONCLUSIONS: Malignant infiltration of the liver should be taken into account in
the differential diagnosis of rapidly progressive liver failure. Although
effective chemotherapy has improved the survival of patients with metastatic
liver disease, there has been no change in the course and outcome of acute liver
failure due to malignant infiltration of the liver over the last 2 decades. A
proper diagnosis by liver biopsy is mandatory to prevent such patients from being
considered for liver transplant.
PMID- 17036531
TI - Multifocal biliary cystadenocarcinoma of the liver: CT and pathologic findings.
AB - Biliary cystadenocarcinoma is a rare tumor that originates from the hepatobiliary
epithelium. Although this tumor can affect any portion of the biliary tree,
intrahepatic location is more common. It is usually a slow growing tumor and
often asymptomatic until it reaches a considerable size. The lesion is most often
solitary and large when discovered; multiple lesions or metastases within the
liver are very rare. A 63-year-old man was referred to our institute for weight
loss, abdominal discomfort, worsening bulky symptoms in the right upper abdominal
quadrant, and an increase in serum aminotransferases that had been present for
several months. Spiral CT of the abdomen demonstrated two lesions, a larger one
and a distant intrahepatic lesion, with a multiloculated cystic aspect, a thin
peripheral capsule, multiple solid peripheral portions, and irregular septa
enhancing in the portal phase after intravenous administration of iodinated
contrast medium. The diagnosis of multifocal cystadenocarcinoma of the liver was
confirmed by surgical laparoscopy and biopsy of the lesion. The patient was
treated with chemotherapy.
PMID- 17036532
TI - Jaw avascular bone necrosis associated with long-term use of bisphosphonates.
PMID- 17036533
TI - Overprotective caregivers of elderly cancer patients: a case report.
AB - The essential role of the caregiver in the management of elderly cancer patients
is still poorly documented. This case report concerns a woman with metastatic
lung carcinoma who was sincerely informed and successfully treated with
chemotherapy and gefitinib only after gaining the trust of her overprotective
daughter. Devoting time to the relatives represents a key element to create a
communicative and efficient relationship with older cancer patients.
PMID- 17036534
TI - Safety of epirubicin adjuvant chemotherapy in a breast cancer patient with
chronic renal failure undergoing hemodialytic treatment.
AB - Anthracycline-based adjuvant chemotherapy is very effective in early breast
cancer, but there are limited data on the use of epirubicin in patients with
chronic renal failure undergoing hemodialytic treatment. We report the case of a
patient with early breast cancer and chronic renal failure who was treated with
adjuvant weekly epirubicin. Treatment was well tolerated. The patient is still
alive and relapse free 58 months after surgery. If the patient will be disease
free after 5 years, she will be reconsidered for renal transplantation. In
conclusion, weekly epirubicin appears to be a safe adjuvant chemotherapy option
for early breast cancer patients with chronic renal failure undergoing
hemodialytic treatment.
PMID- 17036535
TI - A case of bone involvement in hairy cell leukemia successfully treated with
radiation therapy.
AB - We report the case of a 63-year-old man with a clearly established diagnosis of
hairy cell leukemia, treated with multiple lines of chemotherapy, who complained
of localized pain in the left humerus. Radiological findings showed a dystrophic
blastic area within the humeral head. Fine-needle biopsy confirmed the hypothesis
of bone involvement of hairy cell leukemia. The patient underwent radiotherapy at
a dose of 25 Gy, obtaining a complete clinical response with resolution of pain
and a partial recovery of the normal radiological structure of the humerus after
2 months. In addition to the case report, we present a short review of the
literature focusing on the role of radiotherapy in this subset of patients.
PMID- 17036536
TI - [ASCO 2006. Exemestane: a new drug for the adjuvant therapy of breast cancer].
PMID- 17036537
TI - [ASCO 2006 Annual Meeting, Atlanta, June 2-6, 2006. Focus on gastrointestinal
tumors].
PMID- 17036538
TI - Pediatric caries worldwide: implications for oral hygiene products.
AB - International data on pediatric caries epidemiology confirms that tooth decay
remains a significant and consequential disease of childhood that is increasingly
localized in a subset of at-risk children in both developing and developed
countries. A conceptual schema is presented to characterize the occurrence of
caries in child populations, and observations are made regarding the
countervailing impact of simple sugars and fluoride in these populations.
Temporal changes in caries distribution suggest that targeted dental caries
management protocols are increasingly indicated to more effectively manage the
particular risk and caries activity of individual children. Criteria for
successful protocols are discussed in light of both caries pathogenesis and
international recommendations to improve children's oral health.
PMID- 17036539
TI - Dental caries: an infectious and transmissible disease.
AB - By definition, dental caries is an infectious and transmissible disease because
it is caused by bacteria colonizing the tooth surfaces. Unlike most infectious
diseases affecting humans, caries is the result of an imbalance of the indigenous
oral biota rather than a nonindigenous, exogenous pathogen. The introduction of
refined sugar into modern society's diet has tipped the balance from health to
disease. New insight into the natural history of the leading cariogenic bacteria,
the mutans streptococci, may contribute ways to control or prevent this
infectious disease. Here, we use the host-parasite model as a platform for
viewing the pathogenicity of the caries process in contrast to other infectious
diseases.
PMID- 17036540
TI - Clinical considerations for an infant oral health care program.
AB - The American Academy of Pediatric Dentistry and the American Association of
Pediatrics recommend dental assessments and evaluations for children during their
first year of life. Early dental intervention evaluates a child's risk status
based on parental interviews and oral examinations. These early screenings
present an opportunity to educate parents about the medical, dental, and cost
benefits of preventive--rather than restorative-care and may be more effective in
reducing early childhood caries than traditional infectious disease models. A
comprehensive infant oral care program includes: (1) risk assessments at
regularly scheduled dental visits; (2) preventive treatments such as fluoride
varnishes or sealants; (3) parental education on the correct methods to clean the
baby's mouth; and (4) incentives to encourage participation in ongoing
educational programming. Recruiting mothers during pregnancy improves the
likelihood that they will participate in the assessment program. To maximize
interest, trust, and success among participating parents, educational and
treatment programs must be tailored to the social and cultural norms within the
community being served.
PMID- 17036541
TI - Early dental caries detection as a part of oral health maintenance in young
children.
AB - There is an ever-growing need to manage the results of dental caries in young
children. Other articles in this supplement discuss age-specific recommendations
regarding caries management in children. This article will introduce the idea of
using technology to assess caries risk in children and also will identify
alternative technologies that could be used to detect caries lesions as early as
possible. It is hoped that by learning about some of the new technologies that
can be used in caring for children's dental needs, a new cadre of general
practitioners will be willing to take on a portion of the important role of
caring for our children.
PMID- 17036542
TI - Oral health promotion in children and adolescents.
AB - One of the primary goals of dental health professionals is to prevent disease in
our patients. As our knowledge of the disease process improves, so does our
ability to manage the consequences of disease. Oral diseases, such as dental
caries, can be devastating to both children and adolescents. Dental caries may
interfere with a child's ability to eat, sleep, and learn, and it can have a
significant impact on their self-esteem. Because caries affects individuals
disproportionately, it is essential that those at the highest risk are identified
early so that preventive therapies can be targeted toward those who are most
likely to benefit. This article discusses the consequences of oral diseases in
school-aged children, the factors that contribute to an individual's risk for
dental caries, and the most effective therapies to prevent caries in this age
group.
PMID- 17036543
TI - Consumer assessment of toothbrushes designed for children of different ages.
PMID- 17036544
TI - Intergenerational social mobility: the United States in comparative perspective.
AB - Emily Beller and Michael Hout examine trends in U.S. social mobility, especially
as it relates to the degree to which a person's income or occupation depends on
his or her parents' background and to the independent contribution of economic
growth. They also compare U.S. social mobility with that in other countries. They
conclude that slower economic growth since 1975 and the concentration of that
growth among the wealthy have slowed the pace of U.S. social mobility. In
measuring mobility, economists tend to look at income and sociologists,
occupation. The consensus among those measuring occupational mobility is that the
average correlation between the occupations of fathers and sons today ranges from
0.30 to 0.40, meaning that most variation in the ranking of occupations is
independent of social origins. Those measuring income mobility tend to agree that
the elasticity between fathers' and sons' earnings in the United States today is
about 0.4, meaning that 40 percent of the difference in incomes between families
in the parents' generation also shows up in differences in incomes in the sons'
generation. Beller and Hout show that occupational mobility increased during the
1970s, compared with the 1940s-1960s, but there is some evidence to suggest that
by the 1980s and 1990s it had declined to past levels. Existing data on income
mobility show no clear trends over time, but increases in economic inequality
during the 1980s made mobility more consequential by making economic differences
between families persist for a longer time. In international comparisons, the
United States occupies a middle ground in occupational mobility but ranks lower
in income mobility. Researchers have used the variation in mobility to study
whether aspects of a country's policy regime, such as the educational or social
welfare systems, might be driving these results. There is as yet, however, no
scholarly consensus about the sources of cross-national differences in mobility.
PMID- 17036545
TI - Intergenerational mobility for women and minorities in the United States.
AB - Now that some of the historic barriers to economic success for U.S. women and
minorities have begun to fall, women and blacks, in particular, are moving upward
on the nation's socioeconomic ladder. Melissa Kearney reviews evidence that
improved economic opportunities for these two groups make sex and race less
important than they once were in determining economic status. But sex- and race
based differences in wages and income persist, and interactions between sex and
class and between race and class continue to play a role in the intergenerational
transmission of income status. Kearney surveys studies and data showing that
marriage remains important in determining women's economic status, even though
marriage rates among women aged eighteen to thirty-four have been falling--from
73 percent in 1960 to 44 percent in 2000. Not only do spousal earnings continue
to dominate family income for married women, but also women tend to marry men
whose position in the income distribution resembles their fathers' position.
Marriage thus facilitates the transmission of economic status from parents to
daughters. Racial wage gaps persist, says Kearney, largely because of differences
in education, occupation, and skill. It also appears likely that the effects of
discrimination, both current and past, continue to impede racial economic
convergence. Kearney notes that the transmission of income class from parents to
children among blacks differs noticeably from that among whites. Black parents
and white parents pass their economic standing along to children at similar
rates. But because mean income is lower among blacks than among whites, the
likelihood of upward mobility in the overall income distribution is substantially
lower among blacks. Black children are much more likely than white children to
remain in the lower percentiles of the income distribution, and white children
are more likely to remain in the upper reaches of the income distribution.
Downward mobility from the top quartile to the bottom quartile is nearly four
times as great for blacks as for whites.
PMID- 17036546
TI - Making it in America: social mobility in the immigrant population.
AB - In his survey of research on social mobility and U.S. immigration, George Borjas
underscores two insights. First, most immigrants are at a sizable earnings
disadvantage, relative to native-born workers. Second, the earnings of different
groups of immigrants vary widely. The children of immigrants "catch up" to native
born workers slowly. The jump in relative wages between the first and second
generations is somewhere between 5 and 10 percentage points. Of particular
concern is that the age-adjusted relative wage of both immigrants and second
generation workers has been falling--a trend with bleak implications for the
children of immigrants. The wide ethnic variation in the earnings of immigrants
has equally important implications. National origin groups from advanced
economies, such as Canada, do much better in the U.S. labor market than those
from poorer countries, such as Mexico. And the initial ethnic differences tend to
persist. In rough terms, about half of the difference in relative economic status
persists from one generation to the next. Thus a 20 percentage point wage gap
among ethnic groups in the immigrant generation implies a 10 point gap among
second-generation groups and a 5 point gap among third-generation groups. Again
in rough terms, Borjas attributes about half of that persistence to the ethnic
environment in which children are raised. Borjas cautions that the rate of social
mobility that immigrants enjoyed over much of the twentieth century may not
continue in the future. The employment sectors seeking immigrants today are
unlikely to provide the same growth opportunities as did the rapidly expanding
manufacturing sector a century ago. And in contrast to the many and diverse
ethnic groups that made up early twentieth-century immigrants, the large ethnic
groups of immigrants today may develop separate economies and social structures,
in effect hindering their social mobility.
PMID- 17036547
TI - Early childhood development and social mobility.
AB - Steven Barnett and Clive Belfield examine the effects of preschool education on
social mobility in the United States. They note that under current policy three-
and four-year-old children from economically and educationally disadvantaged
families have higher preschool attendance rates than other children. But current
programs fail to enroll even half of poor three- and four-year-olds. Hispanics
and children of mothers who drop out of school also participate at relatively low
rates. The programs also do little to improve learning and development. The most
effective programs, they explain, are intensive interventions such as the model
Abecedarian and Perry Preschool programs, which feature highly qualified teachers
and small group sizes. State preschool programs with the highest standards rank
next, followed by Head Start and the average state program, which produce effects
ranging from one-tenth to one-quarter of those of the best programs. Typical
child care and family support programs rank last. Barnett and Belfield point out
that preschool programs raise academic skills on average, but do not appear to
have notably different effects for different groups of children, and so do not
strongly enhance social mobility. In such areas as crime, welfare, and teen
parenting, however, preschool seems more able to break links between parental
behaviors and child outcomes. Increased investment in preschool, conclude Barnett
and Belfield, could raise social mobility. Program expansions targeted to
disadvantaged children would help them move up the ladder, as would a more
universal set of policies from which disadvantaged children gained
disproportionately. Increasing the educational effectiveness of early childhood
programs would provide for greater gains in social mobility than increasing
participation rates alone. The authors observe that if future expansions of
preschool programs end up serving all children, not just the poorest, society as
a whole would gain. Benefits would exceed costs and there would be more economic
growth, but relative gains for disadvantaged children would be smaller than
absolute gains because there would be some (smaller) benefits to other children.
PMID- 17036548
TI - U.S. elementary and secondary schools: equalizing opportunity or replicating the
status quo?
AB - Although education pays off handsomely in the United States, children from low
income families attain less education than children from more advantaged
families. In this article, Cecilia Elena Rouse and Lisa Barrow investigate why
family background is so strongly linked to education. The authors show that
family socioeconomic status affects such educational outcomes as test scores,
grade retention, and high school graduation, and that educational attainment
strongly affects adult earnings. They then go on to ask why children from more
advantaged families get more or better schooling than those from less advantaged
families. For low-income students, greater psychological costs, the cost of
forgone income (continuing in school instead of getting a job), and borrowing
costs all help to explain why these students attain less education than more
privileged children. And these income-related differences in costs may themselves
be driven by differences in access to quality schools. As a result, U.S. public
schools tend to reinforce the transmission of low socioeconomic status from
parents to children. Policy interventions aimed at improving school quality for
children from disadvantaged families thus have the potential to increase social
mobility. Despite the considerable political attention paid to increasing school
accountability, as in the No Child Left Behind Act, along with charter schools
and vouchers to help the children of poor families attend private school, to date
the best evidence suggests that such programs will improve student achievement
only modestly. Based on the best research evidence, smaller class sizes seem to
be one promising avenue for improving school quality for disadvantaged students.
High teacher quality is also likely to be important. However, advantaged
families, by spending more money on education outside school, can and will partly
undo policy attempts to equalize school quality for poor and nonpoor children.
PMID- 17036549
TI - The role of higher education in social mobility.
AB - Most Americans expect the nation's colleges and universities to promote the goal
of social mobility to make it possible for anyone with ability and motivation to
succeed. But according to Robert Haveman and Timothy Smeeding, income-related
gaps both in access to and in success in higher education are large and growing.
In the top-tier colleges and universities, almost three-quarters of the entering
class is from the highest socioeconomic quartile. The pool of qualified youth is
far greater than the number admitted and enrolled; hence America's top colleges
could enroll more moderate- and low-income students without lowering their
selection standards. Higher-income parents make enormous efforts to ensure their
children's academic success, while children of poor parents begin the "college
education game" later and with fewer resources. Students in poor and minority
neighborhoods are less well prepared academically; ill prepared to select
colleges, apply for admission, and secure acceptance; and poorly informed about
the cost of attending college and the availability of needs-based financial aid.
Sharply rising college prices during the 1980s and 1990s, together with the
growing inequality of family income, have raised the cost of attending college
far more for low-income students than for well-to-do students. Financial aid has
risen more slowly, and the share targeted on low-income students has been
falling. The authors offer bold policy recommendations to increase educational
opportunities for low- and middle-income students. These involve the development
of financing structures that will increase access for students from lower-income
families. Public institutions could price tuition close to real costs and use
added revenues to provide direct student aid for students from low-income
families. Federal subsidies to students who attend wealthy institutions could be
capped, with the savings redirected to students attending less well-endowed
schools, both public and private. Finally, federal and state governments could
redirect to lower-income students the financial support they now provide colleges
and universities.
PMID- 17036550
TI - Children's health and social mobility.
AB - Children from low-income families are more likely than other children to have
serious health problems. And, as Anne Case and Christina Paxson show, childhood
health problems can prevent poor children from achieving economic success as
adults. Income-related disparities in childhood health are evident at birth or
even before, and the disparities grow more pronounced as children grow older. Not
only do poor children have more severe health problems than wealthier children,
but they fare less well than wealthier children who have the same problems. They
also receive less and lower-quality medical care for their problems. And poor
families may be less well equipped to manage their children's health problems,
which could worsen their effects. The available U.S. data sets do not allow
researchers to track individuals' health and economic well-being from birth into
adulthood, but three British data sets are producing growing evidence that health
in childhood is a determinant of educational attainment, which in turn affects
adults' employment opportunities and wages. Children in poor health are also more
likely to have poor health as adults, and their health as adults adversely
affects their economic status. Case and Paxson note that eliminating income
related disparities in health problems in childhood would do little to reduce
earnings disparities between richer and poorer adults. However, they emphasize
that, for children in poor health, improvement in physical condition in childhood
would lead to substantial improvement in economic circumstances. The authors cite
several areas, including expanded prenatal care, maternal smoking cessation
programs, and nutrition programs, as deserving particular attention. They contend
that increased access to health care is not sufficient to improve children's
health. The next wave of policies should focus on improving the quality of health
care and strengthening the ability of parents to manage their children's health
problems.
PMID- 17036551
TI - "Culture" and the intergenerational transmission of poverty: the prevention
paradox.
AB - Many U.S. policymakers support changing the "culture" of poor parents to
encourage marriage, work, and religion as a means to end the intergenerational
transmission of poverty. In this article Jens Ludwig and Susan Mayer review and
evaluate research on how parental work, marriage, and religion affect children's
socioeconomic status as adults, as well as on the likelihood that changing these
indicators of parental behavior will reduce poverty in the next generation. They
conclude that even if policymakers were able to ensure that all children had
married, working, and religious parents, the result would be a far smaller
reduction in poverty among the children's generation than many people believe.
The explanation for this "poverty-prevention paradox," say Ludwig and Mayer, is
that the poverty rate in the children's generation depends not only on how many
poor children grow up to be poor adults, but also on how many nonpoor children
grow up to be poor adults. Reducing the chances that poor children become poor
adults will dramatically lower future poverty rates only if most poor adults
begin life as poor children. But most poor adults grow up as nonpoor children in
the type of "pro-social" households that policymakers are pushing to attain.
Moreover, little good evidence supports the idea that such parental behaviors as
marriage, work, and religious adherence have strong causal effects on children's
long-term economic success. The authors argue that encouraging positive social
behaviors in the parents of poor children is a worthwhile goal in its own right.
But they stress that policymakers should recognize the limits of this strategy
for reducing poverty among future generations. There may be no substitute for a
system of social insurance and income transfers for those children who do wind up
poor as adults.
PMID- 17036552
TI - Benign intrapulmonary teratoma.
PMID- 17036553
TI - Oral contraceptive use and breast cancer risk: current status.
PMID- 17036554
TI - Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta
analysis.
AB - OBJECTIVE: To perform a meta-analysis of case-control studies that addressed
whether prior oral contraceptive (OC) use is associated with premenopausal breast
cancer. METHODS: We searched the MEDLINE and PubMed databases and bibliography
reviews to identify case-control studies of OCs and premenopausal breast cancer
published in or after 1980. Search terms used included breast neoplasms, oral
contraceptives, contraceptive agents, and case-control studies. Studies reported
in all languages were included. Thirty-four studies were identified that met
inclusion criteria. Two reviewers extracted data from original research articles
or additional data provided by study authors. We used the DerSimonian-Laird
method to compute pooled odds ratios (ORs) and confidence intervals (CIs) and the
Mantel-Haenszel test to assess association between OC use and cancer. RESULTS:
Use of OCs was associated with an increased risk of premenopausal breast cancer
in general (OR, 1.19; 95% CI, 1.09-1.29) and across various patterns of OC use.
Among studies that provided data on nulliparous and parous women separately, OC
use was associated with breast cancer risk in both parous (OR, 1.29; 95% CI, 1.20
1.40) and nulliparous (OR, 1.24; 95% CI, 0.92-1.67) women. Longer duration of use
did not substantially alter risk in nulliparous women (OR, 1.29; 95% CI, 0.85
1.96). Among parous women, the association was stronger when OCs were used before
first full-term pregnancy (FFTP) (OR, 1.44; 95% CI, 1.28-1.62) than after FFTP
(OR, 1.15; 95% CI, 1.06-1.26). The association between OC use and breast cancer
risk was greatest for parous women who used OCs 4 or more years before FFTP (OR,
1.52; 95% CI, 1.26-1.82). CONCLUSION: Use of OCs is associated with an increased
risk of premenopausal breast cancer, especially with use before FFTP in parous
women.
PMID- 17036555
TI - Pyridostigmine, diethyltoluamide, permethrin, and stress: a double-blind,
randomized, placebo-controlled trial to assess safety.
AB - OBJECTIVE: To determine whether short-term human exposure to pyridostigmine
bromide, diethyltoluamide, and permethrin, at rest or under stress, adversely
affects short-term physical or neurocognitive performance. PARTICIPANTS AND
METHODS: A multicenter, prospective, double-blind, placebo-controlled crossover
trial exposing 64 volunteers to permethrin-impregnated uniforms, diethyltoluamide
containing skin cream, oral pyridostigmine, and corresponding placebos was
performed. Each participant had 4 separate sessions, ensuring exposure to all
treatments and placebos under both stress and rest conditions in random order.
Outcomes Included physical performance (handgrip strength and duration, stair
climbing, and pull-ups [males] or push-ups [females]), neurocognitive performance
(computerized tests), and self-reported adverse effects. RESULTS: Permethrin was
undetectable in the serum of all participants; pyridostigmine levels were higher
Immediately after stress (41.6 ng/mL; 95% confidence Interval, 35.1-48.1 ng/mL)
than rest (23.0 ng/mL; 95% confidence Interval, 19.2-26.9 ng/mL), whereas
diethyltoluamide levels did not significantly differ by stress condition. Heart
rate and systolic blood pressure increased significantly with stress compared
with rest but did not vary with treatment vs placebo. Physical and neurocognitive
outcome measures and self-reported adverse effects did not significantly differ
by exposure group. CONCLUSION: Combined, correct use of pyridostigmine,
diethyltoluamide, and permethrin is well tolerated and without evidence of short
term physical or neurocognitive impairment.
PMID- 17036556
TI - Assessing the ability of topiramate to improve the daily activities of patients
with migraine.
AB - OBJECTIVE: To assess the impact of topiramate on the daily activities of patients
with migraine. PATIENTS AND METHODS: We performed a randomized, double-blind,
placebo-controlled multicenter trial Initiated on March 1, 2001, and completed on
April 4, 2002. Patient-reported data from the Migraine Specific Questionnaire
(MSQ) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36)
were collected at baseline and at weeks 8, 16, and 26 from an intent-to-treat
population receiving either topiramate, 50, 100, or 200 mg/d, or placebo. Two
activity-related MSQ domains (role restrictive [MSQ-RR] and role prevention [MSQ
RP]) and 2 activity-related SF-36 domains (role physical [SF36-RP] and vitality
[SF36-VT]) were the prospectively designated secondary outcome measures. The
changes in MSQ and SF-36 scores for each treatment group were calculated by
measuring the area under the curve from week 8 (the beginning of the maintenance
period) through week 26 of the double-blind phase, relative to the prospective
baseline. A mixed-effect piecewise linear regression model was used to estimate
average domain score over time. RESULTS: Patients receiving topiramate, 100 or
200 mg/d, had significantly reduced mean monthly (28-day) migraine frequency (P =
.008 and P < .001, respectively) compared with placebo, but not patients
receiving topiramate, 50 mg/d (P = .48). Topiramate significantly improved mean
MSQ-RR domain scores (50 mg/d [P = .02], 100 mg/d [P< .001], and 200 mg/d [P <
.001]) and mean MSQ-RP domain scores (50 mg/d [P = .007], 100 mg/d [P = .001],
and 200 mg/d [P= .002]) vs placebo. Topiramate, 100 and 200 mg/d, significantly
improved mean SF36-RP domain scores vs placebo (P = .02). Topiramate (all doses)
improved SF36-VT domain scores, although not significantly vs placebo. Changes in
prospectively designated domain scores were significantly correlated with changes
in mean monthly migraine frequency (P < or = .001 [MSQ domains], P < or = .002
[SF-36 domains]). CONCLUSION: Patient-reported migraine-specific outcomes
measured by the MSQ-RR and MSQ-RP domains improved significantly for those
receiving topiramate (all doses) vs placebo. The SF36-RP domain scores improved
significantly for patients receiving 100 or 200 mg/d of topiramate. Improvements
in all 4 prospectively selected MSQ and SF-36 domains were significantly
correlated with decreases in mean monthly migraine frequency.
PMID- 17036557
TI - Effect of valacyclovir on viral shedding in immunocompetent patients with
recurrent herpes simplex virus 2 genital herpes: a US-based randomized, double
blind, placebo-controlled clinical trial.
AB - OBJECTIVE: To determine the efficacy of daily suppressive therapy with a 1-g dose
of valacyclovir in reducing total (clinical and subclinical) herpes simplex virus
2 (HSV-2) shedding compared with placebo in Immunocompetent patients diagnosed as
having recurrent HSV-2 genital herpes. PATIENTS AND METHODS: From June 18, 2004,
to December 17, 2004, patients from 27 US sites with a history of 6 or more
genital herpes recurrences per year were randomized in a 3:1 ratio to receive 1
g/d of valacyclovir or placebo. During the double-blind suppressive therapy,
patients were provided with the study drug (500-mg valacyclovir caplets or
matching placebo) and Instructed to take 2 caplets once daily without regard to
meals for 60 days. Daily genital and anal or rectal swabs were self-collected
during the 60-day study period for evaluation of HSV-2 viral shedding as
determined by quantitative type-specific polymerase chain reaction assay.
RESULTS: One hundred fifty-two patients were randomized into this study, 43 to
placebo and 109 to 1 g/d of valacyclovir. A total of 134 completed the study (40
placebo [93%], 94 valacyclovir [86%]), and 18 prematurely withdrew (3 placebo
[7%], 15 valacyclovir [14%]). Valacyclovir significantly reduced the percentage
of days with total (clinical and subclinical) HSV-2 shedding throughout 60 days
compared with placebo. In the intent-to-treat population, a 71% reduction in
total shedding (P < .001), a 58% reduction in subclinical shedding (P < .001),
and a 64% reduction in clinical shedding (P = .01) were observed. Valacyclovir
was not associated with any significant toxic effects compared with placebo.
CONCLUSION: This study demonstrated that 1 g/d of valacyclovir administered for
60 days was generally well tolerated and was an effective suppressive therapy
that significantly reduced total (clinical and subclinical) HSV-2 shedding
compared with placebo in immunocompetent patients diagnosed as having recurrent
HSV-2 genital herpes.
PMID- 17036558
TI - Coverage of coma in headlines of US newspapers from 2001 through 2005.
AB - OBJECTIVE: To review journalists' preferences and accuracy in reporting comatose
states. METHODS: Using the Lexis-Nexis database, we selected newspaper headlines
from January 1, 2001, through December 31, 2005, that included the words coma,
comatose, unconsciousness, vegetative state, awakening, and brain dead. RESULTS:
We identified 340 stories by headlines. The median age of persons in coma was 26
years. Coma cases in men were twice as common as those in women. In 71% of coma
cases, the cause of coma was associated with motor vehicle crashes or violence.
Persistent vegetative state was reported in 25 articles (7%), frequently when a
family or physician conflict emerged. In 33 stories (10%), coma was medically
induced but not mentioned in the headline. Three "miracle" recoveries involved
resumption of speech in patients in a minimally conscious state. CONCLUSION: Few
news reports had gross inaccuracies or misrepresentations; however, definitional
difficulties of unconscious states with the reporters remain. The reporting of
coma may be biased toward violence and trauma. Medically induced coma was present
in 1 of 10 reports but rarely mentioned in the headline.
PMID- 17036559
TI - Extradigital glomus tumors: a 20-year experience.
AB - OBJECTIVE: To review a large series of extradigital glomus tumors in order to
gain a better understanding of their presentation and provide guidelines to aid
in their diagnosis and treatment. PATIENTS AND METHODS: We performed a
retrospective review of all extradigital glomus tumors seen at our institution
during a 20-year period (1985-2005) to document the incidence of the classic
triad of symptoms, the duration of symptoms, the contribution of imaging to
making a definitive diagnosis, and the effectiveness of treatment. RESULTS: Fifty
six different patients with extradigital glomus tumors presented as follows:
glomus tumors in the hand (3), wrist (4), forearm (11), elbow (4), arm (4),
shoulder (2), buttock (1), thigh (5), knee (10), leg (3), ankle (2), foot (2),
back (1), nose (1), cheek (1), ear lobe (1), and trachea (1). Forty-eight
patients presented with pain and localized tenderness, but only 1 patient
presented with cold Intolerance. The average duration of symptoms was greater
than 7 years, with most patients being evaluated previously and having their
conditions misdiagnosed. Magnetic resonance imaging proved to be the most useful
modality for localization of these lesions. Surgical resection was the definitive
treatment and generally provided immediate and sustained pain relief.
CONCLUSIONS: Extradigital glomus tumors are not a rare subgroup of glomus tumors.
Treatment outcomes are excellent, but misdiagnosis and delayed diagnosis are
common. Improved guidelines regarding symptoms and diagnosis of these neoplasms
may reduce the morbidity, ensuing chronic pain, and psychiatric consequences of
delayed diagnosis or misdiagnosis.
PMID- 17036560
TI - Prevalence of restless legs syndrome among native South Americans residing in
coastal and mountainous areas.
AB - OBJECTIVE: To determine the prevalence of restless legs syndrome (RLS) in native
South Americans and identify the impact of geographic location. PARTICIPANTS AND
METHODS: An epidemiological telephone survey of RLS symptoms involving natives
from coastal and mountainous areas was performed during July 2, 2004, through
September 28, 2004. The process consisted of 2 phases: the creation of the
epidemiological instrument and the telephone survey. RESULTS: Five hundred
adults, 250 from the mountainous regions and 250 from the coastal region (190 men
and 310 women; age range, 25-85 years) were interviewed and subsequently divided
on the basis of International Restless Legs Syndrome Study Group criteria into
those who had RLS (RLS+ group) and those who did not (RLS- group). Ten (2.0%) had
RLS. The overall rate of RLS in adults living in the mountainous region at 2816 m
above sea level (3.2% [8/250]) was significantly higher than that for adults
living in the coastal region at 4 m above sea level (0.80% [2/250]; P = .002).
The mean age of the RLS+ group was 49.5 years (SD, 15.20 years; range, 25-85
years). CONCLUSION: Native South American adults have a prevalence of RLS well
below that reported in populations with European ancestry but similar to that in
Asian and Turkish populations. Furthermore, in Ecuador, geographic differences
were identified in areas of similar population density.
PMID- 17036562
TI - Psychiatric adverse effects of corticosteroids.
AB - Psychiatric adverse effects during systemic corticosteroid therapy are common.
Two large meta-analyses found that severe reactions occurred in nearly 6% of
patients, and mild to moderate reactions occurred in about 28%. Although
disturbances of mood, cognition, sleep, and behavior as well as frank delirium or
even psychosis are possible, the most common adverse effects of short-term
corticosteroid therapy are euphoria and hypomania. Conversely, long-term therapy
tends to induce depressive symptoms. Dosage is directly related to the incidence
of adverse effects but is not related to the timing, severity, or duration of
these effects. Neither the presence nor the absence of previous reactions
predicts adverse responses to subsequent courses of corticosteroids.
Corticosteroid-induced symptoms frequently present early in a treatment cycle and
typically resolve with dosage reduction or discontinuation of corticosterolds. In
severe cases or situations in which the dose cannot be reduced, antipsychotics or
mood stabilizers may be required. This review offers an approach to identifying
and managing corticosteroid-induced psychiatric syndromes based on the type of
symptoms and anticipated duration of corticosteroid treatment.
PMID- 17036561
TI - Use of antidementia agents in vascular dementia: beyond Alzheimer disease.
AB - Vascular dementia (VaD) is the second leading cause of dementia and is often
underdiagnosed. Stroke is the leading cause of VaD, although it may also develop
secondary to a variety of other cerebrovascular or cardiovascular conditions.
Currently, no drugs are approved for the treatment of VaD. However, because
cholinergic deficits have been found in patients with VaD, similar to those found
in patients with Alzheimer disease (AD), it is believed that cholinesterase
inhibitors, which are indicated for the treatment of mild to moderate AD, may
also provide benefit for patients with VaD. Clinical trials of donepezil,
galantamine, and rivastigmine have supported this idea, although as yet, large
scale, prospective studies in VaD have only been reported for donepezil.
Donepezil was shown to provide benefits in cognition, global function, and
activities of daily living compared with placebo. The N-methyl-D-aspartate
receptor antagonist memantine may also provide some cognitive benefit in VaD,
particularly in patients with more advanced disease. These data suggest that
antidementia drugs currently used for treatment of AD should be considered for
treatment of VaD as well.
PMID- 17036563
TI - Copper deficiency myelopathy (human swayback).
AB - The hematologic manifestations of copper deficiency are well known and include
anemia and neutropenia. In the past few years, the neurological manifestations of
acquired copper deficiency in humans has been recognized, the most common being a
myelopathy presenting with a spastic gait and prominent sensory ataxia. The known
causes of acquired copper deficiency include prior gastric surgery, excessive
zinc ingestion, and malabsorption; however, often the cause is unclear.
Hyperzincemia may be present even in the absence of exogenous zinc ingestion. The
clinical features and neuroimaging findings are similar to the subacute combined
degeneration seen in patients with vitamin B12 deficiency. Copper and vitamin B12
deficiency may coexist. The neurological syndrome may be present without the
hematologic manifestations. Copper supplementation resolves the anemia and
neutropenia promptly and completely and may prevent the neurological
deterioration. Improvement, when it occurs, is often subjective and
preferentially involves sensory symptoms. This article describes patients with
copper deficiency myelopathy seen at the Mayo Clinic in Rochester, Minn, and
reviews the literature on neurological manifestations of acquired copper
deficiency in humans.
PMID- 17036565
TI - 37-year-old woman with headache.
PMID- 17036564
TI - Answers to frequently asked questions about migraine.
AB - Migraine is a common primary headache disorder associated with pronounced
disability and hence marked economic and public health Implications. Appropriate
treatment is warranted to limit the associated disability migraineurs experience.
Because of the heterogeneity of migraine, treatment plans must be individualized.
The purpose of this article is to provide answers to frequently asked questions
regarding the management of migraine.
PMID- 17036566
TI - Tumor lysis syndrome associated with reduced immunosuppression in a lung
transplant recipient.
AB - Tumor lysis syndrome usually occurs after Initiation of chemotherapy or radiation
therapy in cancer patients with a moderate to high tumor burden. To our
knowledge, the occurrence of this syndrome after discontinuation or reduction of
an immunosuppressive regimen has not been reported in the literature. We describe
a patient who had undergone lung transplantation and who was receiving
immunosuppression and experienced an episode of acute pancreatitis. During the
course of the work-up, the patient was found to have a B-cell lymphoma
(posttransplantation lymphoproliferative disease). His tacrolimus dosage was
decreased, and azathioprine was discontinued. The patient subsequently developed
tumor lysis syndrome. Other than the decrease in immunosuppression, we found no
other factor that could have accounted for this syndrome.
PMID- 17036567
TI - The role of exercise in the prevention and treatment of compression fractures.
PMID- 17036568
TI - Trends in the impact factor of scientific journals.
PMID- 17036569
TI - A brief reply to Carson Strong.
AB - Carson Strong's reply to my response to his article demonstrates what happens
when there is unacknowledged disagreement about the facts of a case or about the
meaning of the terms used to describe those facts. I hope that our dialogue will
help reduce this disagreement.
PMID- 17036570
TI - The need for pain control during scaling and root planing.
AB - Scaling and root planing is a common procedure in clinical practice. Despite the
frequency of the procedure, the control of pain associated with scaling and root
planing has not been well studied. Recently, studies have pointed out a need for
pain control during the procedure in a significant number of subjects-perhaps as
many as 30% of patients. This need for pain control is similar to the need for
instrumentation during maintenance therapy. The need also is similar whether hand
instrumentation or ultrasonic equipment is used. The current most used form of
pain control is local anesthesia injections. However, many patients object to the
use of "the needle." Therefore, there is a need for a noninjectable form of pain
control that is effective.
PMID- 17036571
TI - Efficacy of an intrapocket anesthetic for scaling and root planing procedures: a
review of three multicenter studies.
AB - In recent years, three multicenter studies have been conducted to evaluate the
clinical efficacy of an active 5% dental gel to reduce pain when placed into
periodontal pockets before initiating scaling and root planing procedures. In
each of the clinical studies, the researchers found statistically significant
differences between the pain scores of the active dental gel group and the
placebo gel group that favored the active gel for the control of pain during
periodontal scaling and root planing procedures. This article reviews each of the
three studies and highlights some of the differences among them.
PMID- 17036572
TI - Quantification of patient fears regarding dental injections and patient
perceptions of a local noninjectable anesthetic gel.
AB - Data have shown that 30% of all Americans do not seek dental care and/or
treatment unless a problem arises that causes them severe pain. Similar study
results have been found in Europe as well. While some studies indicate that cost
concerns prevent people from seeking dental care, the fear of pain has been
identified as a factor in keeping people from seeing a dentist. A random sample
of US and European patients who had recently undergone a scaling and root planing
procedure was surveyed via telephone interview to quantify data on patient
concerns and fears regarding anesthesia administered by injection, as well as to
determine patient interest and price perception of an anesthetic gel product. The
survey also provided data on the patient's experience and perception about the
scaling and root planing procedure. Responses from the study population showed
that patients find the injection painful and do not like the prolonged numbness.
Additionally, based on the patients surveyed, they experience injection anxiety
before appointments, and a significant number of them cancel appointments or
simply do not seek treatment because they are afraid of the injection. Finally,
the study also demonstrated that, while not eliminating dental anxiety
completely, the availability of a new noninjectable anesthetic would assist in
relieving patient fear, with almost half of the patients surveyed being more
likely to seek treatment if only the new noninjectable anesthetic was used.
Additionally, most patients surveyed would be willing to pay for the
noninjectable anesthetic out of their own pockets if it was not covered by their
health insurance.
PMID- 17036573
TI - Extreme obesity: a new medical crisis in the United States.
AB - The prevalence of obesity has markedly increased in the past few decades, and
this disorder is responsible for more health care expenditures than any other
medical condition. The greater the body mass index (BMI) (calculated as weight in
kilograms divided by the square of height in meters), the greater the risk of
comorbidities, including diabetes mellitus, hypertension, obstructive sleep
apnea, many cancers, dyslipidemia, cardiovascular disease, and overall mortality.
Class III (extreme) obesity, defined as a BMI of 40 kg/m2 or greater, has also
increased such that it now affects almost 1 in 20 Americans. The prevalence of
extreme obesity is greater among women than among men and greater among blacks
than among non-Hispanic whites or Hispanics. The effect of extreme obesity on
mortality is greater among young than among older adults, greater among men than
among women, and greater among whites than among blacks. The current permissive
environment that promotes increased dietary energy intake and decreased energy
expenditure through reduced daily physical activity coupled with genetic
susceptibility is an important pathogenic factor. The number of bariatric
surgical procedures performed annually is relatively small but increasing.
PMID- 17036574
TI - Assessment and preparation of patients for bariatric surgery.
AB - The number of bariatric surgical procedures performed in the United States has
increased steadily during the past decade. Currently accepted criteria for
consideration of bariatric surgery include a body mass index (calculated as
weight in kilograms divided by the square of height in meters) of 40 kg/m2 or
greater (or >35 kg/m2 with obesity-related comorbidities), documented or high
probability of failure of nonsurgical weight loss treatments, and assurance that
the patient is well informed, motivated, and compliant. Appropriate patient
selection is important in achieving optimal outcomes after bariatric surgery. In
this article, we review our approach to the medical and psychological assessment
of patients who want to undergo bariatric surgery. The medical evaluation is
designed to identify and optimally treat medical comorbidities that may affect
perioperative risks and long-term outcomes. The psychiatric and psychological
assessment identifies factors that may influence long-term success in maintaining
weight loss and prepares the patient for the lifestyle changes needed both before
and after surgery.
PMID- 17036575
TI - Surgical approaches to obesity.
AB - Bariatric surgery has evolved considerably since the introduction of jejunoileal
bypass in the 1950s. With modifications of early procedures, implementation of
new techniques, and establishment of minimally invasive approaches, operative
intervention has become the mainstay in the treatment of extreme (class III)
obesity. The laparoscopic adjustable gastric band technique is the most common
purely restrictive procedure. Advantages of the laparoscopic adjustable gastric
band include reduced perioperative morbidity and mortality compared to other
bariatric procedures, but this procedure has been associated with substantial
intermediate and long-term complications. Although vertical banded gastroplasty
was associated with decreased perioperative morbidity and acceptable early weight
loss, results from long-term follow-up have been discouraging. Roux-en-Y gastric
bypass (RYGB) is the most common bariatric procedure performed in the United
States because of its effectiveness in long-term weight loss and low rates of
serious complications. Modifications of RYGB to induce malabsorption have led to
greater weight loss but increased risks of metabolic and nutritional sequelae.
Duodenal switch is a malabsorptive procedure associated with excellent weight
loss and resolution of weight-related comorbidities, but concerns regarding
potential metabolic and nutritional sequelae have limited its widespread use.
Laparoscopic approaches to bariatric procedures have reduced wound-related
complications and improved patient recovery. However, the incidence of
anastomotic leak and internal hernia is higher after laparoscopic RYGB compared
to the open approach. Each of the currently available bariatric procedures has
both advantages and disadvantages that must be considered in determining which
operation should be selected for an individual patient.
PMID- 17036576
TI - Perioperative care of patients undergoing bariatric surgery.
AB - The epidemic of obesity in developed countries has resulted in patients with
extreme (class III) obesity undergoing the full breadth of medical and surgical
procedures. The popularity of bariatric surgery in the treatment of extreme
obesity has raised awareness of the unique considerations in the care of this
patient population. Minimizing the risk of perioperative complications that
contribute to morbidity and mortality requires input from several clinical
disciplines and begins with the preoperative assessment of the patient. Airway
management, intravenous fluid administration, physiologic responses to
pneumoperitoneum during laparoscopic procedures, and the risk of thrombotic
complications and peripheral nerve injuries in extremely obese patients are among
the factors that present special intraoperative challenges that affect
postoperative recovery of the bariatric patient. Early recognition of
perioperative complications and education of the patient regarding postoperative
issues, including nutrition and vitamin supplementation therapy, can improve
patient outcomes. A suitable physical environment and appropriate nursing and
dietetic support provide a safe and dignified hospital experience. This article
reviews the multidisciplinary management of extremely obese patients who undergo
bariatric surgery at the Mayo Clinic.
PMID- 17036577
TI - Clinical management after bariatric surgery: value of a multidisciplinary
approach.
AB - Comprehensive and collaborative longitudinal care is essential for optimal
outcomes after bariatric surgery. This approach is important to manage the many
potential surgical and medical comorbidities in patients who undergo bariatric
surgery. Medical management programs require prompt and often frequent adjustment
as the nutritional program changes and as weight loss occurs. Familiarity with
the recommended nutritional program, monitoring and treatment of potential
vitamin and mineral deficiencies, effects of weight loss on medical comorbid
conditions, and common postoperative surgical issues should allow clinicians to
provide excellent care. Patients must understand the importance of regularly
scheduled medical follow-up to minimize potentially serious medical and surgical
complications. Because the long-term success of bariatric surgery relies on
patients' ability to make sustained lifestyle changes in nutrition and physical
activity, we highlight the role of these 2 modalities in their overall care. Our
guidelines are based on clinical studies, when available, combined with our
extensive clinical experience. We present our multidisciplinary approach to
postoperative care that is provided after bariatric surgery and that builds on
our presurgical evaluation.
PMID- 17036578
TI - Long-term outcome of bariatric surgery: an interim analysis.
AB - With the increasing number of bariatric surgical procedures being performed,
outcome assessment is of even greater importance. Few randomized, controlled
prospective trials have compared bariatric surgery to nonsurgical weight-loss
treatments, and the quality of current outcome data is suboptimal. However, the
available evidence suggests that bariatric surgery, and particularly gastric
bypass, is the most effective weight-loss treatment for people with extreme
(class III) obesity. In addition to reduced energy intake and to a lesser extent
malabsorption, numerous other potential mechanisms related to bariatric surgery
may play a role in promoting weight loss and improving comorbidities. After
bariatric surgery, clinical improvement or resolution has been reported in 64% to
100% of patients with diabetes mellitus, 62% to 69% of patients with
hypertension, 85% of patients with obstructive sleep apnea, 60% to 100% of
patients with dyslipidemia, and up to 90% of patients with nonalcoholic fatty
liver disease. A wide range of other weight-related conditions also appear to
improve, and limited data suggest that overall mortality may decrease in patients
undergoing bariatric surgery. Although not conclusive, evidence from available
studies indicates that bariatric surgery is cost-effective. Further research with
improved methodology is needed to define the mechanisms of action of bariatric
surgery; to document its effect on long-term weight loss, comorbid conditions,
and overall mortality; and to determine its cost-effectiveness.
PMID- 17036579
TI - What price a healthy profession?
PMID- 17036580
TI - An unavoidable and unmistakable link.
PMID- 17036581
TI - Controversy is absence of fact.
PMID- 17036582
TI - Dental assisting law amended to expand duties for certified dental assistants.
PMID- 17036583
TI - Trends in oral piercing in Buffalo, New York, high schools.
AB - The purpose of this research was to examine the trend of high school adolescents
obtaining an oral piercing. A questionnaire was sent to five high schools in
Buffalo, NY. Of the 508 questionnaires returned, 49 of the respondents (10%) had
an oral piercing. Post-piercing occurrences included swelling, tenderness,
numbness, loss of taste, bleeding and pus. Oral piercing maintenance was minimal
or non-existent. Dental trauma/piercing-related injuries were common. Researchers
concluded that the oral piercing trend in Buffalo, NY, high schools is small;
however, students who are getting oral piercings are doing so without parental
consent and often show signs of infection.
PMID- 17036584
TI - Use of SIG device to accurately place permanent miniature dental implants to
retain mandibular overdenture. A case report.
AB - A case of mini-dental implant insertion for retention of a mandibular overdenture
in a hospitalized patient has been documented. The additional use of the SIG
(drill guide) directional device in the implant placement protocol gave the
practitioner more confidence and resulted in the proper alignment of the three
ball-top, one-piece fixtures. The three implants were inserted exactly 1 cm apart
and parallel to each other. The distal fixtures were approximately 1 cm away from
the mental foramina, thereby eliminating the risk of lip paresthesia. Keeper caps
were placed in the denture's intaglio after one month. The keeper caps allowed
for proper retention of the overdenture. The caps also enabled the patient to
easily insert and withdraw his denture, even though he displayed limited manual
dexterity. The tissue response was excellent, and oral hygiene was made easier
with adequate spacing of the exposed ball-tops. The overall experience for both
the operator and the patient was very positive. General dentists should be able
to readily master this technique and add it to their armamentarium for the
benefit of all their patients.
PMID- 17036585
TI - Surgical management of iatrogenic root perforation following endodontic therapy.
AB - Endodontic mishaps still occur despite technological advancements in the field of
dental instrumentation and materials. Iatrogenic root perforations during access
preparation, canal instrumentation or preparation of post space are not uncommon,
and instrument fractures during filing or reaming, as well as root fractures
during condensation, are also encountered. Many of these mishaps are hard to
avoid because of the extreme variability in root canal anatomy, canal
calcification, abnormal root shapes and curvatures. They occur most often during
access preparation, root cleaning, shaping and preparation of post space, or when
attempting to bypass fractured instruments. Procedural errors impede endodontic
therapy, thus increasing the risk of treatment failure, especially in teeth with
necrotic pulps and periradicular lesions. Clinicians often have difficulty
diagnosing and treating root perforations and the treatment of such mishaps is
very difficult, especially in posterior teeth and in the area of the mandibular
furcation. We report on a case of root perforation in a mandibular first molar
that was successfully treated by surgery without the use of additional
biomaterials.
PMID- 17036586
TI - Diagnosis and clinical significance of dens invaginatus to practicing dentist.
AB - Dens invaginatus, commonly known as dens in dente, is a developmental
malformation of teeth that most commonly affects permanent maxillary lateral
incisors. Deciduous teeth are infrequently affected. Presence of dens invaginatus
in mandibular permanent teeth is extremely uncommon. A rare presentation of
coronal double dens invaginatus incidentally detected in a mandibular canine
tooth on radiographic examination is being reported, along with a discussion of
this anomaly. The patient had presented for routine dental treatment unrelated to
this finding. In addition, the various radiographic appearances of dens
invaginatus, as they present within the maxillary and mandibular teeth, are
described. Essential clinical considerations and treatment options are presented.
A review of the pertinent literature is undertaken, and tables summarizing
previously published reports of mandibular dens invaginatus and double dens
invaginatus are presented. A review of the literature indicates that dens
invaginatus in mandibular teeth is extremely rare, with only 11 other cases,
involving 14 teeth, reported previously. Cases of double dens invaginatus are
even more atypical, with only eight previously reported cases. Dens invaginatus
is an anomaly that should be familiar to all practicing dentists because of the
clinical implications and potential sequelae.
PMID- 17036587
TI - Find canals faster through basic research.
AB - Achieving access and finding canals are the key first steps in the endodontic
procedure. This has always been a time-consuming, qualitative procedure that
relies on the dentist's experience and feel. Recent basic research has been
published that shows that the anatomic morphological measurements concerning the
pulp chamber are very consistent in every tooth. This research points the way to
a quantitative, predictable and quick technique for making endodontic access
preparations without risk. The research and clinical technique are described in
this article.
PMID- 17036588
TI - Stabilization of endotracheal tube--a technical note.
AB - The vital need to retain closed-circuit airways during maxillofacial surgery has
led to several innovations in anesthetic tube placement and stabilization.
Several designs and alterations of endotracheal tubes have been described and are
currently in use. These range from suturing the tubing to the patient's scalp to
fabricating maxillofacial prostheses. In this report, an easy method for securing
anesthetic tubes is described. This technique has been used successfully at our
institution.
PMID- 17036589
TI - Cystic hygroma.
AB - Cystic hygroma (CH) is a benign, developmental condition of unknown etiology. 90%
of the cases are present by age 2. CH represents malformed lymphatics that fail
to communicate with larger veins and, therefore, they collect lymph. It is a type
of lymphangioma. The clinical presentation is one of a painless, soft mass that
reaches a giant size and can lead to the death of the infant. The diagnosis is
done with CT scan and biopsy. We report a severe case of CH and describe the
difficult surgical treatment, despite the benign nature of the lesion.
PMID- 17036590
TI - Survey of sedation techniques used Among pediatric dentists in New York State.
AB - The purpose of this study was to evaluate pediatric dentists in New York State
who use oral sedation. Results indicated that fewer than 50% of pediatric
dentists used oral sedatives in their office, but that of these dentists, more
than 50% reported that their sedations are successful.
PMID- 17036591
TI - Highlighting nurses' contribution to patient care: Examining nurse-sensitive
outcomes.
PMID- 17036592
TI - Oncology nursing: Finding the balance in a changing health care system.
AB - Health care restructuring has resulted in significant changes in the workload and
work environment for oncology nurses. While recent studies describe the impact of
these changes on the general nursing workforce in several countries, there have
been no published studies that have focused on worklife issues of Canadian
oncology nurses. Therefore, a qualitative study was conducted to gain insight
about how oncology nursing has changed over the past decade and how Canadian
oncology nurses are managing these changes. Analysis of telephone interviews with
51 practising oncology nurses employed across Canada revealed three major themes.
The first theme, "health care milieu", portrayed a picture of the cancer care
environment and patient and professional changes that occurred over the past
decade. The second theme, "conflicting demands", reflects how the elements of
change and social forces have challenged professional oncology nursing practice.
The third theme, "finding the way", describes the patterns of behaviour that
nurses used to manage the changing health care environment and make meaning out
of nurses' work in cancer care. Overall, the findings portray a picture of
Canadian oncology nurses in "survival mode". They face many workplace challenges,
but are able to keep going "for now" because they find ways to balance their
responsibilities on a daily basis and because they know and believe that their
specialized nursing knowledge and skills make a difference in patient care.
PMID- 17036593
TI - Redefining the primary nurse role in oncology care: A 21st century perspective.
AB - Oncology nursing is a rapidly evolving specialty with increasing demands upon
nurses to respond to the complex needs of cancer patients and their families.
Primary nursing (PN) has been the model of care delivery utilized at our cancer
centre for more than two decades. The nursing department determined it was time
that a review and redefining of the role be undertaken. These objectives were
achieved through the implementation of the Primary Nurse Role Development
Project. This article discusses: a brief background of why the existing role
needed to be reviewed and revised; an overview of how primary nursing has been
applied historically at the centre; and details regarding the project plan and
its implementation. Results from the project provided a competency-based oncology
primary nurse role description, which will be outlined along with proposals for
improving nursing practice. Our goal is to achieve optimal care for our patients.
PMID- 17036594
TI - Caring for the caregivers: Innovative program for oncology nurses.
AB - An innovative program, Care for the Professional Caregiver, was designed to
provide staff nurses in a cancer program with the opportunity to learn about
coping with stress in their practice. The program was evaluated using
quantitative and qualitative methods. The findings clearly describe the benefits
of the program on both a short- and long-term basis. The value of connecting with
other cancer nurses, supporting each other, and sharing stories about their work
life experiences resulted in benefits to the nurse as an individual, as a team
member, and as a professional practitioner. The program achieved its aims and is
recommended for ongoing implementation.
PMID- 17036595
TI - Not "simply" teaching another chemotherapy patient...
PMID- 17036596
TI - Preventive medicine in Task Force 1st Armored Division during Operation Iraqi
Freedom.
AB - Task Force 1st Armored Division (TF1AD) deployed to Baghdad and South Central
Iraq from April 2003 through July 2004. TF1AD preventive medicine had
responsibility for ensuring divisional force health protection, including soldier
health, disease and nonbattle injury mitigation, health promotion, and civil
affairs operations. Heat injury, diarrheal disease, skin and respiratory disease,
and eye and musculoskeletal injury rates were high. Command emphasis and
preventive medicine action resulted in better living conditions and personal
sanitation. To counter the threat, the TF1AD preventive medicine/ division
surgeon team used a "spiraling out" approach that focused attention first on hand
washing, potable water, vector control, waste disposal, and food sanitation and
later on noise, asbestos, environmental contamination, and radiation. In April
2004, TF1AD shifted focus to the Multinational Division Central-South region of
Iraq and many similar problems occurred as in May 2003, although they were less
severe, in part because of the lessons learned in Baghdad.
PMID- 17036597
TI - Noninvasive hemodynamic monitoring for combat casualties.
AB - The aims of this study were to develop and to test a noninvasive hemodynamic
monitoring system that could be applied to combat casualties to supplement
conventional vital signs, to use an advanced information system to predict
outcomes, and to evaluate the relative effectiveness of various therapies with
instant feedback information during acute emergency conditions. In a university
run inner city public hospital, we evaluated 1,000 consecutively monitored trauma
patients in the initial resuscitation period, beginning shortly after admission
to the emergency department. In addition to conventional vital signs, we used
noninvasive monitoring devices (cardiac index by bioimpedance with blood pressure
and heart rate to measure cardiac function, arterial hemoglobin oxygen saturation
by pulse oximetry to reflect changes in pulmonary function, and tissue
oxygenation by transcutaneous oxygen tension indexed to fractional inspired
oxygen concentration and carbon dioxide tension to evaluate tissue perfusion).
The cardiac index, mean arterial pressure, pulse oximetry (arterial hemoglobin
oxygen saturation), and transcutaneous oxygen tension/fractional inspired oxygen
concentration were significantly higher in survivors, whereas the heart rate and
carbon dioxide tension were higher in nonsurvivors. The calculated survival
probability was a useful outcome predictor that also served as a measure of
severity of illness. The rate of misclassification of survival probability was
13.5% in the series as a whole but only 6% for patients without severe head
injuries and brain death. Application of noninvasive hemodynamic monitoring to
acute emergency trauma patients in the emergency department is feasible, safe,
and inexpensive and provides accurate hemodynamic patterns in continuous, on
line, real-time, graphical displays of the status of cardiac, pulmonary, and
tissue perfusion functions. Combined with an information system, this approach
provided an early outcome predictor and evaluated, with an objective
individualized method, the relative efficacy of alternative therapies for
specific patients.
PMID- 17036598
TI - Bacteria recovered from patients admitted to a deployed U.S. military hospital in
Baghdad, Iraq.
AB - The predominant bacteria and antimicrobial susceptibilities were surveyed from a
deployed, military, tertiary care facility in Baghdad, Iraq, serving U.S. troops,
coalition forces, and Iraqis, from August 2003 through July 2004. We included
cultures of blood, wounds, sputum, and urine, for a total of 908 cultures; 176 of
these were obtained from U.S. troops. The bacteria most commonly isolated from
U.S. troops were coagulase-negative staphylococci, accounting for 34% of
isolates, Staphylococcus aureus (26%), and streptococcal species (11%). The 732
cultures obtained from the predominantly Iraqi population were Klebsiella
pneumoniae (13%), Acinetobacter baumannii (11%), and Pseudomonas aeruginosa
(10%); coagulase-negative staphylococci represented 21% of these isolates. These
differences in prevalence were all statistically significant, when compared in
chi2 analyses (p < 0.05). Antimicrobial susceptibility testing demonstrated broad
resistance among the Gram-negative and Gram-positive bacteria.
PMID- 17036599
TI - Bacteriology of war wounds at the time of injury.
AB - Bacterial contamination of war wounds occurs either at the time of injury or
during the course of therapy. Characterization of the bacteria recovered at the
time of initial trauma could influence the selection of empiric antimicrobial
agents used to prevent infection. In the spring of 2004, U.S. military casualties
who presented to the 31st Combat Support Hospital in Baghdad, Iraq, with acute
traumatic injuries resulting in open wounds underwent aerobic culture of their
wounds to identify the bacteria colonizing the wounds. Forty-nine casualties with
61 separate wounds were evaluated. Wounds were located predominantly in the upper
and lower extremities and were primarily from improvised explosive devices or
mortars. Thirty wounds (49%) had bacteria recovered on culture, with 40 bacteria
identified. Eighteen casualties (20 wounds) had undergone field medical therapy
(irrigation and/or antimicrobial treatment); six of these had nine bacterial
isolates on culture. Of the 41 wounds from 31 patients who had received no
previous therapy, 24 grew 31 bacteria. Gram-positive bacteria (93%), mostly skin
commensal bacteria, were the predominant organisms identified. Only three Gram
negative bacteria were detected, none of which were characterized as broadly
resistant to antimicrobial agents. The only resistant bacteria recovered were two
isolates of methicillin-resistant Staphylococcus aureus (MRSA). Our assessment of
war wound bacterioly soon after injury reveals a predominance of Gram-positive
organisms of low virulence and pathogenicity. The presence of MRSA in wounds
likely reflects the increasing incidence of community-acquired MRSA bacteria.
These data suggest that the use of broad-spectrum antibiotics with efficacy
against more resistant, Gram-negative bacteria, such as Pseudomonas aeruginosa
and Acinetobacter spp., is unnecessary in early wound management.
PMID- 17036600
TI - Skin lesions in barracks: consider community-acquired methicillin-resistant
Staphylococcus aureus infection instead of spider bites.
AB - Recent outbreaks of mysterious skin lesions on multiple personnel at several
military facilities were initially blamed on spiders. Requests were made for pest
inspection and control to remedy the situation. Greater scrutiny of the situation
led to a hypothesis that instead of spiders, an infectious outbreak of community
acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) should be
investigated as the etiology. Subsequent culturing of the lesions on personnel at
one facility confirmed this bacterial etiology. Barracks, as well as other close
quarter military living conditions, are ripe environments for the establishment,
persistence, and spread of CA-MRSA. Military medical personnel should consider CA
MRSA as a more likely etiologic agent than spider bites for cutaneous eruptions
in which there are multiple lesions on one person or multiple patients with
similar lesions.
PMID- 17036601
TI - Acanthamoeba keratitis in a U.S. Army soldier after unauthorized use of contact
lenses in the combat theater.
AB - A 25-year-old active duty Army E-5 developed severe infectious keratitis in his
left eye secondary to soft contact lens (CL) wear while deployed in Iraq,
necessitating evacuation to Walter Reed Army Medical Center for further
evaluation and treatment. Initial clinical examination at Walter Reed Army
Medical Center was suggestive of Acanthamoeba keratitis, a serious corneal
pathogen associated with CL wear. In vivo confocal microscopy demonstrated
Acanthamoeba cysts in the epithelium and anterior stroma, and smears and cultures
from an epithelial biopsy specimen confirmed the diagnosis of Acanthamoeba
keratitis. To our knowledge this is the first reported case of Acanthamoeba
keratitis in a soldier wearing CLs in the combat theater. Because of the
inability to maintain proper lens hygiene in a combat or field environment, the
risk of developing a potentially sight-threatening corneal infection is
significant. This unfortunate case of a devastating eye infection serves as a
reminder of the current Army policy, which prohibits the use of CLs during gas
chamber exercises, field training, and combat.
PMID- 17036602
TI - Transvaginal hysterectomy for enlarged leiomyomata uteri in a Medical Department
Activity environment.
AB - During a 6-year period, 119 patients with enlarged leiomyomata uteri underwent a
transvaginal hysterectomy at this medium-size Medical Department Activity using
morcellation to debulk the uterus. One hundred seventeen underwent successful
removal of the uterus with the use of various morcellation techniques to reduce
the uterine size. Two patients required conversion to an abdominal procedure. A
retrospective review of each operative report was completed, and the findings are
presented in this study. There was a low morbidity rate in this series, with no
deaths. Transvaginal hysterectomy with debulking of enlarged leiomyomata using
morcellation is a safe alternative to abdominal hysterectomy in a Medical
Department Activity environment.
PMID- 17036603
TI - Pelvic pain presenting in a combat environment.
AB - OBJECTIVE: The objective was to identify the incidence of pain disorders in the
deployed female active duty population in support of Operation Iraqi Freedom.
METHODS: Retrospective chart review was completed on all patients who were seen
for gynecologic services at Camp Doha, Kuwait, from September 2003 through March
2004. One thousand seven hundred thirty-seven patients were identified.
Statistical analysis was performed. RESULTS: Of the 1,737 patients seen during
the study period, 150 patients were identified as having a pelvic pain disorder.
These patients accounted for 14% of all patients seen for gynecologic services.
Mean age was 28 +/- 8 years (range, 15-53 years). Pelvic pain of unclear etiology
and cystitis were the most common diagnoses made accounting for 19% and 16% of
encounters. CONCLUSIONS: Acute pelvic pain disorders can be effectively managed
in the combat environment. Optimization of predeployment regimens for management
of pain is strongly recommended. Consideration should be given to making soldiers
with chronic pelvic pain disorders that fail to respond to predeployment medical
management nondeployable.
PMID- 17036604
TI - Suicide and the air force mental health provider: frequency and impact.
AB - Although suicide is relatively common among mental health patients, few studies
have been published detailing the effects of a patient's suicide on his or her
mental health provider. We reviewed data from 97 active duty, Air Force, mental
health providers who responded to an anonymous survey. Forty-eight percent of the
providers had experienced a patient's suicide. One-third of them reported a sense
of responsibility for that patient's death. More than 20% reported significant
emotional or behavioral changes following the death. Many providers experienced
alterations in their self-esteem and their use of peer consultation following the
suicide. Speaking to clergy members, friends, and other providers was generally
beneficial following the suicide of a patient. Recommendations are given to
minimize the impact of this tragedy on providers.
PMID- 17036605
TI - Stress, mental health, and job performance among active duty military personnel:
findings from the 2002 Department of Defense Health-Related Behaviors Survey.
AB - This study examined the extent to which high levels of occupational and family
stress were associated with mental health problems and productivity loss among
active duty military personnel. We analyzed data from the 2002 Department of
Defense Survey of Health-Related Behaviors among Military Personnel, which
provided extensive population-based information on 12,756 active duty personnel
in all branches of the military worldwide. Military personnel reported higher
levels of stress at work than in their family life. The personnel reporting the
highest levels of occupational stress were those 25 or younger, those who were
married with spouses not present, and women. Personnel with high levels of stress
had significantly higher rates of mental health problems and productivity loss
than those with less stress. We recommend that prevention and intervention
efforts geared toward personnel reporting the highest levels of stress be given
priority for resources in this population.
PMID- 17036606
TI - The Trauma Symptom Inventory: factors associated with invalid profiles in a
sample of combat veterans with post-traumatic stress disorder.
AB - The assessment of combat-related post-traumatic stress disorder (PTSD) relies
upon self-reported symptoms and the need for indicators of valid reporting is
critical. The Trauma Symptom Inventory (TSI) is a testing instrument specific to
PTSD which includes validity scales. In a pilot study examining the use of the
TSI with combat veterans, 50 male veterans diagnosed with PTSD were administered
the TSI. Nineteen percent of the profiles were invalid, all but one based on the
Atypical Response Scale. Differences between veterans with valid and invalid TSI
profiles are examined in terms of demographic and historical factors, TSI
profiles, and individual scale items. The model best able to predict invalid
profiles included high scores on subscales measuring dissociative experiences and
tension reduction behaviors. Implications for the interpretation of TSI validity
scales in assessing combat-related PTSD are discussed.
PMID- 17036608
TI - High prevalence of iron deficiency and anemia in female military recruits.
AB - Iron deficiency anemia has long been known to impair physical and mental
performance. Iron deficiency itself, even without anemia, may also cause such an
effect. Similar to female athletes, women in active military units may have
increased risks for iron deficiency and its detrimental effects. Female recruits
were screened for anemia and iron store status, and a questionnaire on lifestyle
habits and menstruation was completed. Iron depletion (serum ferritin level of
<20 microg/L) was found for 77% of study participants. Iron deficiency (ferritin
level of <12 microg/L and transferrin saturation of <15%) was found for 15% of
study participants. Anemia was found for 24% of subjects, and iron deficiency
anemia was found for 10% of subjects. High prevalence of iron depletion, iron
deficiency, anemia, and iron deficiency anemia was found among female recruits
intended for active military duty. Therefore, a recommendation can be made to
screen such female recruits for anemia and iron stores.
PMID- 17036607
TI - Job stress, depression, work performance, and perceptions of supervisors in
military personnel.
AB - OBJECTIVE: Recent studies have identified high levels of job stress in military
personnel. This study examined the relationship among job stress, depression,
work performance, types of stressors, and perceptions about supervisors in
military personnel. METHODS: Eight hundred nine military personnel answered a 43
item survey on work stress, physical and emotional health, work performance,
perceptions about leadership, job stressors, and demographics. RESULTS: More than
one- quarter (27.4%) of this military population reported suffering from
significant job stress. Both the report of work stress and depression were
significantly related to impaired work performance, more days of missed work,
poorer physical health, and negative perceptions about the abilities of
supervisors and commanders. Depression and job stress were significantly and
positively related to each other. CONCLUSIONS: These results support accumulating
data indicating that work stress is a significant occupational health hazard in
the routine military work environment. Targeting and eliminating sources of job
stress should be a priority for the U.S. military to preserve and protect the
mental health of military personnel.
PMID- 17036609
TI - Predictors of aversive alcohol consequences in a military sample.
AB - The purpose of this study was to identify predictors of risky alcohol use and
alcohol-related consequences among postdeployment soldiers. Demobilizing soldiers
completed an assessment packet that included questions about demographic factors,
relationships, stress, and alcohol-related consequences. Significant predictors
of greater alcohol-related consequences, as assessed with the CAGE questionnaire,
included fewer years of formal education, male gender, not being in an intimate
relationship, racial/ethnic minority status, enlisted rank, having been deployed
to the continental United States, and greater stress, whereas significant
predictors of drinking and driving included male gender, not being in an intimate
relationship, and greater stress. Identifying the predictors of alcohol
consequences that occur upon demobilization may aid in determining which soldiers
are at risk for such consequences before deployment and may help to maintain
military readiness.
PMID- 17036610
TI - Surgical nurse practitioners as registered nurse first assists: the role,
historical perspectives, and educational training.
AB - Advanced practice nurses (APN) who practice in the surgical subspecialty areas
may have the opportunity to expand their scope of practice to include first
assistant at surgery. Surgical APNs who practice as registered nurse first
assistants (RNFA) should seek credentialing and apply for institutional
privileges to assure the consumer of competent providers. Credentialing as an
RNFA documents the educational learning process and skills acquired, and
recognizes this area of expertise. The role of the APN as an RNFA at surgery is
practiced within the specialty area of perioperative nursing which includes
preoperative, intraoperative, and postoperative care. In this study, the nurse
practitioners describe the role of the RNFA, its historical evolution over
wartime, the required educational training, and the benefits of the role for
patient care. The surgical nurse practitioner who undertakes training and
education as a surgical RNFA is in an excellent position to provide patient care
across the surgical continuum.
PMID- 17036611
TI - Reliability and validity testing of a short form of the Readiness Estimate and
Deployability Index Revised for Air Force Nurses.
AB - OBJECTIVE: The purpose of this study was to test the reliability and validity of
the Readiness Estimate and Deployability Index Revised for Air Force Nurses Short
Form, with a sample of 205 Air Force nurses. Participants were mostly female
(70%), 36.31 +/- 9.3 years of age, with 11.52 +/- 7.17 years of nursing
experience. METHODS: With structural equation modeling, the initial model did not
fit the data (chi2/df = 5.45) and was revised. RESULTS: Revisions based on
modification indices provided evidence of reliability (alpha coefficients of 0.70
0.94; the majority of R2 values were >0.50) and improved the fit of the model
(chi2 difference, 35.54; df difference, 3.76; p < 0.05). Hypothesis testing
provided evidence of construct validity. CONCLUSIONS: The 40-item Readiness
Estimate and Deployability Index Revised for Air Force Nurses Short Form provides
evidence of reliability and validity as a self-assessment measure of deployment
preparedness.
PMID- 17036612
TI - Humanitarian assistance medicine: perceptions of preparedness: a survey-based
needs assessment of recent U.S. Army internal medicine residency graduates.
AB - The U.S. military provides humanitarian assistance in many areas around the
globe. With recent changes in the force structure of the U.S. Army, internal
medicine physicians are now at the forefront of providing this care, but the
extent of their involvement is not known. This study measured the frequency with
which recently trained Army internists provided humanitarian assistance, and it
assessed their perceived preparedness for such missions. All graduates from Army
internal medicine programs for 4 consecutive years were invited by e-mail to
participate in an Internet-based survey. Eighty-nine personnel (49% of those
contacted) completed the survey. Of those in a deployable position for >6 months,
72% provided medical humanitarian assistance. Most thought that additional
training was needed, especially in tropical disease management, sanitation, and
the practices of civilian humanitarian workers. This study demonstrates that
military-trained internists are frequently involved in humanitarian assistance
medicine, and it suggests that they might benefit from additional training.
PMID- 17036613
TI - Humanitarian assistance in Afghanistan: a prospective evaluation of clinical
effectiveness.
AB - OBJECTIVE: To examine the clinical effectiveness of patient encounters during
humanitarian assistance (HA) missions performed by the 48th Combat Support
Hospital in Afghanistan. METHODS: Data were prospectively gathered from missions
in the villages of Aroki (January 21, 2003), Tangee (March 25, 2003), and Turkman
(April 22, 2003). Health care providers evaluated the effectiveness of each
patient encounter using a data-gathering instrument with clearly defined outcome
measures. RESULTS: A total of 1,887 patients were seen during the three missions.
Forms were incomplete for 112 patients and not used for 33 dental patients. For
the remaining 1,742 individuals, probable cures were achieved as follows: adult
males, 31%; adult females, 52%; male children, 46%; and female children, 54% (all
patients, 46%, p < 0.001). After adjusting for acute care that was supportive in
nature during the final mission, probable cures were achieved as follows: adult
males, 22%; adult females, 16%; male children, 34%; and female children, 27%.
During this final operation, 73% (p < 0.001) of patients received care that was
unnecessary, unlikely to produce a cure, or was merely supportive in nature.
CONCLUSIONS: During HA missions performed by the 48th Combat Support Hospital,
the majority of patient encounters did not result in curative treatments. The
effectiveness of medical care during HA missions cannot be assumed and future
operations should include assessments of outcomes to optimize their value.
PMID- 17036614
TI - Creation of an innovative laser incident reporting form for improved trend
analysis using the Delphi technique.
AB - With expanding numbers of laser applications, there is greater potential for
laser radiation exposures. Proper surveillance and evaluation of laser incidents
can lead to better injury prevention and more efficient medical treatment.
Current laser incident databases do not provide sufficient information for
surveillance and analysis of laser trends. A laser incident reporting form (LIRF)
was created for U.S. Air Force applications by using the Delphi technique. To
create the LIRF, four expert panels were formed by 40 health and safety
professionals experienced with laser systems and medical evaluation of laser
incidents. After three rounds of surveys, the final LIRF contained 100 data
collection fields identifying the most valuable items for injury trend analysis.
Although the LIRF was initially developed to collect USAF laser incident
information, it could potentially act as the cornerstone for a new system serving
the entire military system.
PMID- 17036615
TI - Assessing the validity of the Stages of Change Readiness and Treatment Eagerness
Scale with treatment-seeking military service members.
AB - The purpose of this project was to assess the concurrent and predictive validity
of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) for
military service members undergoing substance abuse treatment. Concurrent
validity was assessed by examining the correlation of SOCRATES subscales with
subscales from the Addiction Treatment Attitude Questionnaire. Predictive
validity was assessed by examining the ability of SOCRATES subscales to predict
length of stay in treatment and successful completion of treatment. Scores on the
SOCRATES were correlated in the expected direction with scores on the Addiction
Treatment Attitude Questionnaire and predicted length of stay in treatment and
successful completion of treatment. The findings provide support for the validity
of the SOCRATES with substance abuse treatment-seeking military service members.
PMID- 17036616
TI - Prevalence of glucose-6-phosphate dehydrogenase deficiency in U.S. Army
personnel.
AB - The U.S. Army recently mandated that soldiers undergo glucose-6-phosphate
dehydrogenase (G6PD) testing before deployment to malarious regions. We
retrospectively characterize the presence and degree of G6PD deficiency in U.S.
military personnel by sex, self-reported ethnicity, and World Health Organization
deficiency classification through test results obtained October 1, 2004 through
January 17, 2005. Data were available for 63,302 (54,874 males and 8,428 females)
subjects; 2.5% of males and 1.6% of females were deficient, with most having only
moderate enzyme deficiency. African American males (12.2%) and females (4.1%),
along with Asian males (4.3%), had the highest rates of G6PD deficiency. Most
males were found to have class III variants while most females were class IV
variants. The most severely deficient were Asian males (class II). These results
suggest that universal screening for G6PD deficiency is clinically warranted, and
particularly essential for those male service members who self-report ethnicity
as African American, Asian, or Hispanic.
PMID- 17036617
TI - Use of a centrifuge-based automated blood cell counter for radiation dose
assessment.
AB - Hematological changes create early-response biomarkers for assessing radiation
doses. Existing dose-prediction models are based on serial blood lymphocyte
counts after acute whole-body exposure to gamma-radiation. Measurements of
lymphocyte-depletion kinetics after possible exposures are useful for triaging
patients and managing medical resources. The small-footprint QBC Autoread Plus
System provides cost-effective hematological analyses with reproducibility,
accuracy, and a broad dynamic range. QBC analysis measures centrifugally packed,
whole blood cells in microhematocrit tubes and reports pooled lymphocyte and
monocyte counts. Our objective was to modify this procedure to report pure
lymphocyte counts for radiation biodosimetry applications. The CD14 antigen is
strongly expressed on most human monocytes. Using anti-CD14-coated Dynabeads, we
have devised a rapid method for depleting monocytes from whole blood without
altering the lymphocyte viability or count. This simple dry procedure provides
reliable lymphocyte counts for results that fall within the normal lymphocyte
count range (1-4 x 10(9) cells per L) for radiation exposure assessment using
lymphocyte-depletion kinetics.
PMID- 17036618
TI - Dolasetron versus ondansetron as single-agent prophylaxis for patients at
increased risk for postoperative nausea and vomiting: a prospective, double
blind, randomized trial.
AB - This study identified 100 ambulatory surgery patients receiving general
anesthesia who were at increased risk for postoperative nausea and vomiting
(PONV) and randomly assigned them to receive single-agent prophylaxis (12.5 mg of
dolasetron or 4 mg of ondansetron) 15 to 30 minutes before the end of surgery.
Data were collected in the postanesthesia care unit, and patients completed a
questionnaire 24 hours after surgery. No statistically significant difference
existed between study groups in demographic features, history of PONV, history of
motion sickness, or type and duration of surgery and anesthesia. No statistically
significant difference existed in satisfaction with the medication used for PONV
prophylaxis (dolasetron, 70.9 of 100 mm; ondansetron, 67.9 of 100 mm; p = 0.69).
No statistically significant difference existed in satisfaction with the overall
surgical experience (dolasetron, 87.9 of 100 mm; ondansetron, 85.3 of 100 mm; p =
0.36). Costminimization strategies should be considered without fear of
substandard care or increased patient dissatisfaction.
PMID- 17036619
TI - Predictors of exercise compliance in individuals with Gulf War veterans
illnesses: Department of Veterans Affairs Cooperative Study 470.
AB - Although the health benefits of exercise for individuals with Persian Gulf War
veterans illnesses (GWVI) are documented, many of these individuals do not
exercise regularly enough to obtain benefits. The purpose of this study was to
investigate factors predicting exercise compliance among individuals with GWVI in
a multicenter, randomized, clinical trial. Participants were 1,092 veterans who
reported at least two of the following cardinal symptoms of GWVI: (1) fatigue,
(2) musculoskeletal pain, and (3) cognitive problems. Participants received
exercise alone or exercise and cognitive-behavioral therapy. The overall level of
compliance was relatively low during the exercise treatment phase (46.2%) and
decreased by one-half during the follow-up period (23.0%). Predictors of
compliance during treatment included less pain and greater age, motivation, and
body mass index. Predictors of compliance during the follow-up period included
less pain and greater age. The results highlight factors that affect adoption and
maintenance of physical activity in a population with GWVI.
PMID- 17036620
TI - Radiology corner. Answer to last month's radiology case and image: left atrial
myxoma.
PMID- 17036621
TI - How independent are those independent studies?
PMID- 17036622
TI - It doesn't have to be this way.
PMID- 17036623
TI - Politically connected.
PMID- 17036624
TI - When the levees broke.
PMID- 17036625
TI - This...or that?
PMID- 17036626
TI - Referrals are good business.
PMID- 17036627
TI - Your Health. Fat and fast food.
PMID- 17036628
TI - Why floss?
PMID- 17036629
TI - You've come a long way, Navy.
PMID- 17036630
TI - Practice what you preach.
PMID- 17036631
TI - Lymphodynamics in the fetus and newborn.
AB - Body fluid is distributed among three major fluid spaces: plasma, interstitial
fluid, and intracellular fluid. The distribution of fluid in each of these
compartments is dramatically different in the fetus and newborn compared to the
adult. In addition, the amniotic fluid that surrounds the fetus may also be
considered an extension of the extracellular space of the fetus. The purpose of
this review is to discuss the complex mechanism that regulates volume in the
fetus and newborn as well as the regulation of fluid distribution between the
plasma and interstitial fluid, while placing special emphasis on the role the
lymphatic system plays in mediating and maintaining this distribution.
PMID- 17036632
TI - Demonstration of tissue alterations by ultrasonography, magnetic resonance
imaging and spectroscopy, and histology in breast cancer patients without
lymphedema after axillary node dissection.
AB - Estimates of the incidence of arm swelling after axillary lymph node dissection
for breast cancer range from 10 to 37%. Yet the subjective sensation of edema is
described in at least 54% of patients. The purpose of this research was to
examine the structural changes occurring in the subcutaneous tissue that might
explain these subjective complaints using multiple imaging modalities. Two female
cadavers with unilateral breast amputation and axillary dissection were studied.
The dermal and subcutaneous layers of both arms were visualized with high
frequency ultrasonography, and magnetic resonance imaging and spectroscopy (MRS),
and tissue biopsies were taken for histological evaluation. On the operated side,
ultrasound imaging showed a hyperechogenic subcutis and the fat-to-water
relationship in adipose cells was higher as measured by MRS. Dissection of the
arms revealed structural adipose tissue changes, which were confirmed by
microscopic evaluation.
PMID- 17036633
TI - Lymphatic clearance of the human skin in patients with acute deep vein thrombosis
using a novel fluorescent technique.
AB - The purpose of this study was to investigate lymphatic clearance of the human
skin in patients with acute deep thrombosis of the femoral vein. In 13 patients
with deep vein thrombosis and no other cause for swelling of the limbs, lymphatic
clearance of the skin at the foot was measured. Ten microliters of fluorescein
isothiocyanatedextran 150,000 were injected intradermally and the fluorescent
light intensity of the deposit measured 10 min and 24 hours after injection by
window densitometry. In addition, intralymphatic pressure was measured by the
servo-nulling system. The results were compared with a sex- and age-matched
control group. Fluorescent light intensity decreased by 23.8 +/- 12.3 arbitrary
units or by a factor of 1.8 +/- 0.5 in patients with DVT after 24 hours, which
was significantly less than in healthy controls (33.7 +/- 8.9 arbitrary units or
by factor 5.0 +/- 4.1, p < 0.013). Intralymphatic pressure was not different
between the two groups. These results indicate that lymphatic clearance is
significantly reduced in the acute phase of deep venous thrombosis.
PMID- 17036634
TI - Biomechanical evaluation of scapular girdle in patients with chronic arm
lymphedema.
AB - The presence of arm lymphedema can induce alterations in motor functions and
posture. Using an optoelectronic system (ELITE 2002), we evaluated these
alterations during a set of tests involving walking, resting and fatigue. The
results of our biomechanical analysis demonstrated a limited range of motion of
the affected arm, particularly a reduction in swinging during walking tests, and
in shoulder retroposition and abduction movements for all patients. After
repeated cyclical movements, premature fatigue appeared in the pathological arm.
Lymphedema does not appear to cause alterations to the posture of the spine in
our study, but drooping of the shoulder homolateral to the lymphedema can occur.
This kind of investigation, which is quick, easy, and comfortable for patients
with lymphedema, can be a useful method to evaluate functional capacity, thus
allowing a quantitative assessment of the loss of function and the optimizing of
the rehabilitative protocol.
PMID- 17036635
TI - Skin excision and groin lymphadenectomy: techniques and outcomes.
AB - A 10-year retrospective review of 25 patients undergoing groin lymphadenectomy
for cutaneous malignancy in the Tayside region of the UK was conducted.
Comparison was made between patients undergoing the procedure with an elliptical
incision orientated as a long oblique of at least 4cm width (group 1) and those
undergoing a similarly oriented incision with no skin excision (group 2). Outcome
measures including survival, postoperative complications, operative time and
hospital stay were analyzed. Patients in group I suffered significantly fewer
complications (p < 0.004) and shorter hospital stay (p < 0.008). Elliptical
excision of at least 4cm width is our preferred technique for groin
lymphadenectomy in the treatment of cutaneous malignancy of the lower limb.
PMID- 17036636
TI - Massive cavernous lymphangioma of the breast and thoracic wall: case report and
literature review.
AB - Lymphangiomas are benign lesions but are associated with high morbidity when they
become very large, occur in critical locations, or when surgically removed,
develop secondary wound infections. Almost all lesions require surgical
treatment. Complete excision is curative; however, relapses must be anticipated
with incomplete excision. We report the case of a patient with a long history of
massive cavernous lymphangioma of the breast and thoracic wall extending into the
axilla in whom complete excision was not possible.
PMID- 17036637
TI - Incidence and characteristics of lymphedema in Turner's syndrome.
AB - A survey of patients with Turner's syndrome and their parents documents the
incidence, features, and prognosis of lymphedema in surviving children.
PMID- 17036638
TI - Restructuring the role of the community pharmacists.
PMID- 17036639
TI - Taking the fork in the road...and changing the world!
PMID- 17036640
TI - 2006 Remington Lecture: the pursuit of dignity.
PMID- 17036641
TI - 2006 Prescott Lecture: lessons learned, lessons shared: what pharmacy needs to do
to make the most of the profession.
PMID- 17036642
TI - Prevalence of compounding in independent community pharmacy practice.
AB - OBJECTIVES: To determine the extent of prescription compounding in independent
community pharmacies and identify factors that influence the decision of
independent pharmacists whether to provide compounding services. DESIGN: Cross
sectional survey. SETTING: Illinois, Missouri, Kansas, and Iowa. PARTICIPANTS:
370 pharmacists in charge. INTERVENTION: Anonymous questionnaire mailed in
January 2005. MAIN OUTCOME MEASURES: Percentage of pharmacies that provide
compounding; percentage of dispensed prescriptions that require compounding;
factors contributing to decisions whether to provide compounding service.
RESULTS: Overall, 94% of respondent pharmacies provided compounding services at
the time of this survey. Prescriptions that required compounding represented less
than 1% of total prescriptions for the majority (58.3%) of respondents. The main
reasons for the decision to provide compounding service were wanting to provide
full pharmaceutical care to patients (73.8% of compounders) and responding to
requests by prescribers (48.7%). Pharmacies that did not provide compounding
service cited the main reason as not receiving prescriptions that required
compounding (63.6% of noncompounders). CONCLUSION: Compounding remains a
component of pharmacy practice in the independent community setting.
Prescriptions that required compounding represented 2.3% of all prescriptions
dispensed by compounding pharmacies.
PMID- 17036643
TI - Use of self-prescribed nonprescription medications and dietary supplements among
assisted living facility residents.
AB - OBJECTIVE: Describe the prevalence of self-prescribed use and misuse as well as
users' opinions concerning nonprescription medications and dietary supplements in
assisted living facilities. DESIGN: Descriptive cross-sectional study. SETTING:
Two assisted living facilities (ALFs) in Oregon and Washington State.
PARTICIPANTS: Convenience sample of 45 ALF residents. INTERVENTION: Chart reviews
and face-to-face interviews. MAIN OUTCOME MEASURES: Prevalence and types of use
of self-prescribed over-the-counter (OTC) medications and dietary supplements;
misuse of these products, and participants' opinions concerning use of these
products. RESULTS: Among 29 women and 16 men with a mean (+/- SD) age of 84.8 +/-
6.9 years and a mean of 9.9 +/- 6.4 years of education, 84.4% were using
selfprescribed OTC medications and dietary supplements at the time of this study.
A mean of 3.4 products was used per participant. Nutritional supplements were
most frequently used (32% of products), followed by gastrointestinal products
(17%), pain relievers (16.3%), herbals (14.4%), topical products (12%), and
cold/cough products (8.5%). Potential misuse was identified in 23 (51%) of the
participants. Problems in the use of products included duplication (70%),
potential drug/disease/food interactions (20.8%), and other inappropriate use
(9.1%). The majority (76%) of the participants believed the products were helpful
in maintaining health, 56% of them wanted more product information, 49% sought
product information from family and friends, 40% turned to their physicians and
nurses for information, and 11% asked pharmacists for advice. CONCLUSION: The use
of nonprescription medications and dietary supplements among ALF residents was
high, and simultaneous use of multiple products with the same active ingredient
was the most prevalent problem. The residents turned to family and friends,
physicians, nurses, and ALF staff for information on these products more
frequently than they did to pharmacists.
PMID- 17036644
TI - Identifying caring behaviors of pharmacists through observations and interviews.
AB - OBJECTIVE: To identify caring behaviors of community pharmacists demonstrated in
the pharmacist-patient interaction. DESIGN: Qualitative research. SETTING: Five
community pharmacies in the Greater Chicago area. PARTICIPANTS: 8 pharmacists
identified as "caring pharmacists" by corporate managers and 13 pharmacy
technicians. INTERVENTIONS: Observations of pharmacy personnel interacting with
patients and interviews of 2 pharmacists. MAIN OUTCOME MEASURES: Caring
behaviors. RESULTS: Four categories of caring behaviors emerged from the
observation field notes: physical behaviors (leaning toward patient, smiling,
looking patient in eye), relationship behaviors (greeting patients, knowing name,
making small talk), task behaviors-nonpharmacy (explaining receipt and money
transaction), and task behaviors-pharmacy (providing information, calling
physician, asking about allergies and explaining interactions). In interviews,
pharmacists said that a caring pharmacist was about "being for the patient," and
both noted that caring pharmacists greet the patient, inquire about the patient's
health and family, and are sincerely interested in the patient. Mentors and
family members are important in developing caring pharmacists, the pharmacists
said. CONCLUSION: Specific caring behaviors identifiable among pharmacists and
pharmacy technicians. These behaviors can be modeled by pharmacy managers and
should be taught in pharmacy schools.
PMID- 17036645
TI - Implementing personal digital assistant documentation of pharmacist interventions
in a military treatment facility.
AB - OBJECTIVE: To describe the use of personal digital assistants (PDAs) in
documenting pharmacists' clinical interventions. SETTING: Evans Army Community
Hospital (EACH), a 78-bed military treatment facility, in Colorado Springs.
PARTICIPANTS: Pharmacists on staff at EACH. PRACTICE DESCRIPTION: All pharmacists
at EACH used PDAs with the pilot software to record interventions for 1 month.
The program underwent final design changes and then became the sole source for
recording pharmacist interventions. The results of this project are being
evaluated every 3 months for the first year and yearly thereafter. PRACTICE
INNOVATION: Visual CE (Syware Inc. Cambridge, Mass.) software was selected to
develop fields for the documentation tool. This software is simple and easy to
use, and users can retrieve reports of interventions from both inpatient and
outpatient sections. The software needed to be designed so that data entry would
only take a few minutes and ad hoc reports could be produced easily. MAIN OUTCOME
MEASURES: Number of pharmacist interventions reported, time spent in clinical
interventions, and outcome of clinical intervention. RESULTS: Implementing a PDA
based system for documenting pharmacist interventions across ambulatory,
inpatient, and clinical services dramatically increased reporting during the
first 6 months after implementation (August 2004-February 2005). After initial
fielding, clinical pharmacists in advanced practice settings (such as disease
management clinic, anticoagulation clinic) recognized a need to tailor the
program to their specific activities, which resulted in a spin-off program unique
to their practice roles. CONCLUSION: A PDA-based system for documenting clinical
interventions at a military treatment facility increased reporting of
interventions across all pharmacy points of service. Pharmacy leadership used
these data to document the impact of pharmacist interventions on safety and
quality of pharmaceutical care provided.
PMID- 17036646
TI - Stepwise approach to developing point-of-care testing services in the
community/ambulatory pharmacy setting.
AB - OBJECTIVE: To provide a stepwise approach to development and implementation of a
point-of-care testing (POCT) patient care service. SETTING: Community and
ambulatory care pharmacy practice. PRACTICE DESCRIPTION: To provide community and
ambulatory pharmacists with the steps involved in integrating POCT services into
their pharmacy practice site. PRACTICE INNOVATION: Authors used various resources
to detail the process of implementing pharmaceutical care in community or
ambulatory pharmacy settings in combination with individual practice experiences.
The five steps involved in developing a POCT service include conducting a needs
assessment, researching and organizing information, developing program materials,
implementing the service, and evaluating the service. The narrative description
of each step is illustrated by a case study example. INTERVENTIONS: Not
applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS/CONCLUSION: POCT
patient care services are a valuable addition to a pharmacy's services,
benefiting patients, health care providers, and the pharmacy. This article
presents a structured, deliberate approach with resources that can be used to
develop a successful POCT service within a community or ambulatory pharmacy
setting.
PMID- 17036647
TI - Preceptors' perspectives on benefits of precepting student pharmacists to
students, preceptors, and the profession.
AB - OBJECTIVES: To educate pharmacists on the shortage of quality preceptors and the
benefits received from precepting; present insights from successful preceptors
and offer guidance to current and prospective preceptors; and encourage
pharmacists to become preceptors and mentor aspiring pharmacy professionals.
SETTING: Advanced experiential settings for Nova Southeastern, Ohio Northern, and
Creighton Universities. PRACTICE DESCRIPTIONS: Hospital, community, and
outpatient clinic settings. PRACTICE INNOVATION: Successful incorporation of
student pharmacists and the experiential process into pharmacy practice. MAIN
OUTCOME MEASURE: Not applicable. RESULTS: A variety of factors has produced an
increased demand for qualified pharmacist preceptors, including workload issues,
an increasing number of pharmacy schools, and an increased experiential load in
the pharmacy school curricula. Characteristics of quality preceptors include
demonstrating enthusiasm in their teaching, being open to questions, and
providing constructive feedback. Sites and preceptors can benefit from teaching
student pharmacists by receiving assistance in developing and maintaining
clinical services, sensing the satisfaction of giving back to the profession, and
material rewards provided by schools of pharmacy. In this article, three
successful preceptors share their perspectives and insights about precepting, and
a professional organization perspective is included to highlight the support for
precepting student pharmacists. CONCLUSION: Additional introductory and advanced
quality pharmacy experiential practice sites are needed, and pharmacists are
encouraged to contact nearby pharmacy schools to become preceptors.
PMID- 17036648
TI - Effect of an automated dispensing system on errors in two pharmacies.
PMID- 17036649
TI - Feasibility of brief smoking cessation intervention in community pharmacies.
PMID- 17036650
TI - Pharmacy-physician communications: potential to reduce medication errors.
PMID- 17036651
TI - Patient education and counseling for drug samples dispensed at physicians'
offices.
PMID- 17036652
TI - Ernest Little (1888-1973): champion of the American Foundation for Pharmaceutical
Education.
PMID- 17036653
TI - Shingles prevention: vaccine presents opportunity to pharmacists.
PMID- 17036655
TI - OTC product: WellPatch Migraine.
PMID- 17036654
TI - New drugs: rasagiline mesylate, conivaptan hydrochloride, and sunitinib malate.
PMID- 17036656
TI - Lifestyle issues and psoriasis.
PMID- 17036657
TI - What is your diagnosis? Periungual squamous cell carcinoma.
PMID- 17036658
TI - Folliculitis decalvans treated with radiation therapy.
AB - A 33-year-old black man presented with folliculitis decalvans resistant to
multiple oral and topical therapies. The patient ultimately responded to
radiation therapy.
PMID- 17036659
TI - Soft tissue augmentation.
AB - Recent additions to the soft tissue augmentation armamentarium have greatly
increased the dermatologic surgeon's choices in optimizing facial contouring and
the treatment of acne scars. In this article, we review the science of fillers
and look at the future of dermal fillers.
PMID- 17036660
TI - Alefacept in the treatment of recalcitrant palmoplantar and erythrodermic
psoriasis.
AB - Alefacept is the first biologic agent approved by the US Food and Drug
Administration for moderate to severe chronic plaque psoriasis. Prior clinical
studies excluded patients with palmoplantar psoriasis or erythroderma. We report
2 patients with recalcitrant psoriasis who responded completely to a full course
of alefacept. One patient presented with severe palmoplantar psoriasis
recalcitrant to acitretin and methotrexate; another patient presented with
erythroderma and was transitioned successfully from cyclosporine A. Alefacept
provides another treatment option for palmoplantar and erythrodermic psoriasis
and should be considered in the management of patients with these conditions.
PMID- 17036661
TI - Therapeutic options for herpes labialis: Experimental and natural therapies.
PMID- 17036662
TI - Cyclopamine: inhibiting hedgehog in the treatment of psoriasis.
AB - The steroidal alkaloid cyclopamine, a direct inhibitor of the hedgehog (Hh)
intracellular signaling pathway, has demonstrated promising initial results in
the treatment of psoriasis. Cyclopamine initially was shown to be effective in
the induction of the differentiation and apoptosis of basal cell carcinomas
(BCCs). This brief review explains both the details of Hh signaling and the role
of cyclopamine in interrupting it. Most importantly, this article discusses the
implications of recent findings on the treatment of psoriasis. Although
considerable research and clinical trials lie ahead, cyclopamine-induced Hh
inhibition may represent the latest mechanistic pathway to combat psoriasis.
PMID- 17036663
TI - Tinea capitis.
AB - Tinea capitis (TC) is a common fungal infection of the scalp, hair follicles, and
hair shafts that can affect any age group but is particularly common in
schoolchildren. The prevalence of TC has risen in the past 2 decades.
Griseofulvin, the gold standard of therapy, does not cure about 20% of patients
with TC, which has led to recent clinical trials on alternative agents for TC.
This article reviews the pertinent new advances in the understanding of the
disease and its therapy.
PMID- 17036664
TI - Sequential use of infliximab and etanercept in generalized pustular psoriasis.
AB - Generalized pustular psoriasis is a dramatic potentially life-threatening
psoriasis variant and represents a major therapeutic challenge. Tumor necrosis
factor alpha (TNF-alpha) inhibitors have been shown to be highly effective in
psoriasis vulgaris and psoriasis arthritis. Currently, TNF-alpha can be targeted
therapeutically by 2 different approaches. TNF-alpha antibodies show a fast onset
of action and a long-lasting activity. Soluble TNF-alpha receptors have a slower
onset and a shorter duration of activity, which allows a rapid cessation of the
drug's activity in the case of adverse events. Here we report that a remission of
generalized pustular psoriasis achieved by the TNF-alpha antibody infliximab was
maintained by long-term application of the soluble TNF-alpha receptor etanercept.
Sequential therapy with TNF-alpha antibodies and TNF-alpha receptors may
represent a novel concept that combines a rapid onset of action in the initiation
therapy with a lower risk for severe adverse events in the maintenance treatment
of pustular psoriasis.
PMID- 17036665
TI - Nonlaser UVB-targeted phototherapy treatment of psoriasis.
AB - Nonlaser localized narrowband (290-315 nm) UVB phototherapy was tested in 10
subjects with localized psoriasis. Treatments were given 2 to 3 times weekly.
Four patients did not complete the planned 25-treatment course. Of the remaining
6 patients, all reached greater than 90% clearing of their disease. Localized
nonlaser UVB phototherapy is another option for the treatment of localized
psoriasis.
PMID- 17036666
TI - Knowledge and use of evidence-based practice by allied health and health science
professionals in the United Kingdom.
AB - Clinical effectiveness (CE) and evidence-based practice (EBP) are the cornerstone
of modern-day health care. Although many studies have explored attitudes and
perceived knowledge of individual professions, few have compared these factors
between professional groups, especially in the allied health professions (AHP)
and health science services (HSS). We report a study comparing the knowledge and
practice of 14 different professional groups from the AHP and HSS in terms of EBP
and CE. The aim was to highlight any differences between the 14 professional
groups along with the needs of the groups. A postal questionnaire survey was
completed by a random sample of 1,000 members of AHP and HSS across the United
Kingdom. There were significant differences between professional groups with, in
general, professionals from the HSS groups rating their knowledge and application
of CE and EBP as lower than members of the AHP. Differences were also noted
between individual professional groups. For example, podiatrists, radiographers,
and orthoptists reported having less knowledge of CE and EBP than
physiotherapists, occupational therapists, dietitians, speech and language
therapists, and psychologists. Barriers to implementing EBP were similar for all
groups, with lack of both time and money cited as the main issues. A number of
differences between professions were recorded that highlight the difference in
educational and policy approach required for greater uptake of EBP.
PMID- 17036667
TI - Emerging trends on tenure policies and practices in nursing and allied health
education.
AB - The tenure system in academia is under attack, and there is a need for empirical
data on the emerging national trends relating to tenure. This comparative study
investigated the emerging trends on tenure policies and practices in nursing and
allied health education. We surveyed the deans of National League for Nursing
accredited programs and deans of allied health programs belonging to the
Association of Schools of Allied Health Professions nationwide. The nursing (n =
187) and allied health (n = 75) deans completed a research questionnaire designed
to capture the critical issues relating to tenure in higher education. We found
no significant difference (p > 0.05) between the perceptions of the allied health
and nursing deans on the policies and practices associated with tenure. The
allied health and nursing deans had similar views on posttenure review, changes
in traditional tenure, tenure quota practice, inducements for faculty to forego
tenure, review of the tenure criteria, and the ranking of the primary criteria
used in granting tenure. Both groups of deans expressed strong support for the
tenure system. Overall, 72% of the allied health deans and 68% of the nursing
deans indicated that a doctorate is the degree required for tenure in their
institutions. The preponderance of allied health and nursing deans, 77% each,
ranked teaching as the primary criterion used in tenure decision. On the other
hand, only 22% of allied health deans and 19% of nursing deans rated research as
the most important criterion used for tenure. Only 1% of allied health deans and
4% of nursing deans considered service as the most important criterion used in
tenure decision. The role of clinical practice in tenure decision was not
evaluated in our study and is worth investigating in follow-up studies.
PMID- 17036668
TI - Attitudes and knowledge of students in the allied health professions toward their
future professional team members.
AB - The investigators wished to explore final-year allied health students' knowledge
of their future colleagues. A survey developed by Felsher and Ross (1994) was
adapted and administered to 35 occupational therapy (OT), 35 physical therapy
(PT), and 35 speech-language pathology (SLP) students. Findings suggested that
all students had a good understanding and knowledge of their own professions.
Differences were found among the three groups of students regarding their
understanding of other disciplines and the overlap in OT and SLP roles.
Specifically, OT and SLP students perceived their own professions as the primary
providers of cognitive treatment. Ways to foster student understanding and
collaboration are suggested.
PMID- 17036669
TI - Development of content-valid technical skill assessment instruments for athletic
taping skills.
AB - BACKGROUND AND PURPOSE: The content validity of technical skill assessment
instruments (TSAI) for the skills of athletic taping has not been reported. The
purpose of this paper is to outline and present the process of content validation
for nine TSAIs for athletic taping. Local and national validators were selected
from Canadian Athletic Therapists' Association (CATA)-accredited athletic therapy
(AT) programs to serve as content validators. METHODS: The process of content
validation began with the creation of a detailed task analysis via mail and
simple validation by local validators. Subsequently, the detailed task analysis
was committee validated by a group of 10 validators from across Canada.
Validators judged the importance and difficulty of each item, and a face-to-face
committee-validator meeting established consensus on the majority of checklist
items. Through a modified Ebel procedure, frequency distribution was used in the
formation of the final TSAIs. RESULTS: Initial consensus for pre-taping
assessment and technical skill performance items was low. Upon committee
discussion and lack of agreement, the decision to remove pretaping assessment
items was made. Initial results of importance and difficulty for athletic taping
technical skills were low prior to the committee meeting. Results of importance
and difficulty improved substantially following the face-to-face committee
validators meeting. Consensus on fail points improved from initial to final
committee validation. CONCLUSION: The process of simple and committee validation
can be seen as effective methods to establish the content validity of instruments
used for the evaluation of athletic taping.
PMID- 17036670
TI - Holding doctors responsible at Guantanamo.
PMID- 17036671
TI - Using the SF-36 to determine perceived health-related quality of life in rural
Idaho seniors.
AB - The purpose of this study was to establish the perceived health-related quality
of life (HRQoL) in people aged 65 and older in rural southeastern Idaho. Ninety
five people aged 65 and older completed the Short Form 36 version 2 (SF-36 v2), a
valid and reliable HRQoL instrument. Subject scores were then compared to
established normative values for the general U.S. adult population and
specifically to normative values for people aged 65 and older. In general, the
participant's HRQoL was lower than that of the general population. However,
females aged 75 and older had higher physical component summary (PCS) scores than
their age- or gender-matched mates, and PCS scores of all participants aged 75
and older were higher than those of their age-matched mates. Results of a
regression analysis indicated that number of prescription medications taken (p =
0.004) was the only variable predictive of PCS scores. The results of this study
show a decrease in the physical aspects of HRQoL of participants, signifying that
HRQoL does decline with age. Results suggest that participants aged 75 and older
have a higher HRQoL than suspected, which could indicate that rural residence is
not an immediate indicator of decreased quality of life in the elderly.
PMID- 17036672
TI - Effects of radiography program admissions practices on student retention.
AB - This study examined the admissions practices of 24-month radiography programs to
determine the extent to which the practices affect retention rates. Survey data
from 327 programs representing 6,443 radiography program matriculants, 5,191
graduates, and 1,252 withdrawals showed that retention rates were significantly
(p < or = 0.05) higher in programs that used a competitive admission process than
in those that did not. Also, it was observed that the use of selective grade
point average and reference letters in the competitive admission process was
significant (p < or = 0.05) in predicting increased retention rates in a
radiography program.
PMID- 17036673
TI - Duty and liability surrounding clinical internships: What every internship
coordinator should know.
AB - Practical work experience has become a common component of many academic
programs. However, there are risks involved when students engage in required
academic internships, particularly if these experiences are conducted off-campus.
In the academic setting, particularly on the campus property, the university has
an established relationship with the student that carries implied contractual
duties. The university's duty to the students, which is to provide them with
educational opportunities and a safe environment, may be upheld even when the
educational activity is occurring off-campus. Recent court rulings indicate that
universities may be held liable for students' safety while these students are
engaged in the fulfillment of education requirements off-campus. Recognizing that
universities cannot control the behavior and choices of students, universities
still have a duty to consistently enforce precautionary safety measures and
forewarn students of any known risks. The delineation and fulfillment of the
university's duty to provide a safe environment and educational opportunities can
be addressed through contractual agreements, policies and procedures, and
communication among the parties. This discussion should assist the internship
coordinator in establishing policies and procedures that meet the required duties
and minimize exposure to liability surrounding internships held off-campus.
PMID- 17036674
TI - Health professions' education and practice: A commentary on transformation
through the internet.
AB - The Internet, in all of its forms and functions, is well on the way to becoming
the most ubiquitous technology of the 21st century. It is changing the way the
world does business, the way formal education is conducted, and the way humans
interact with each other. The Internet already has become an invaluable tool for
formal health education and for the delivery by health professionals of
information, training, and education to their employees and patients. With new
paradigms for health on the horizon, modem Internet technologies will transform
health care practice and systems delivery. In this report, the authors focus
attention on the use of distance learning/distance education technologies and
their relationship to, and use in, the health professions.
PMID- 17036675
TI - Strategies to promote a climate of academic integrity and minimize student
cheating and plagiarism.
AB - Student academic misconduct is a growing problem for colleges and universities,
including those responsible for preparing health professionals. Although the
implementation of honor codes has had a positive impact on this problem, further
reduction in student cheating and plagiarism can be achieved only via a
comprehensive strategy that promotes an institutional culture of academic
integrity. Such a strategy must combine efforts both to deter and detect academic
misconduct, along with fair but rigorous application of sanctions against such
behaviors. Methods useful in preventing or deterring dishonest behaviors among
students include early integrity training complemented with course-level
reinforcement, faculty role-modeling, and the application of selected
testing/assignment preventive strategies, including honor pledges and honesty
declarations. Giving students more responsibility for oversight of academic
integrity also may help address this problem and better promote the culture
needed to uphold its principles. Successful enforcement requires that academic
administration provide strong and visible support for upholding academic
integrity standards, including the provision of a clear and fair process and the
consistent application of appropriate sanctions against those whose conduct is
found to violate these standards.
PMID- 17036676
TI - Core competencies for health care professionals.
PMID- 17036677
TI - The changing face of faculty and governance.
PMID- 17036678
TI - What ever happened to faculty governance?
PMID- 17036679
TI - Faculty matters: Jerry White.
PMID- 17036680
TI - Building a home for the science of nursing education: developing the NLN web
based repository.
PMID- 17036681
TI - Defining the professional responsibilities of academic nurse educators: The
results of a national practice analysis.
AB - In February 2005, the National League for Nursing's Academic Nurse Educator
Certification Program and its testing service partner, Applied Measurement
Professionals, Inc. (AMP), conducted a study designed to determine the
professional practice responsibilities of academic nurse educators. The results
of this national practice analysis, reported here, provided the initial
information required to ensure the development of a practice-related, content
valid certification examination for academic nurse educators.
PMID- 17036682
TI - The evolution of educational information systems and nurse faculty roles.
AB - Institutions of higher education are purchasing and/or designing sophisticated
administrative information systems to manage such functions as the application,
admissions, and registration process, grants management, student records, and
classroom scheduling. Although faculty also manage large amounts of data, few
automated systems have been created to help faculty improve teaching and learning
through the management of information related to individual students, the
curriculum, educational programs, and program evaluation. This article highlights
the potential benefits that comprehensive educational information systems offer
nurse faculty.
PMID- 17036683
TI - Student perceptions of caring in online baccalaureate education.
AB - The concept of caring in nursing education is foundational. Knowledge development
regarding caring in face-to-face classroom settings, effective online teaching
approaches, differences between online and face-to-face classroom settings, and
supporting student success in online settings is extensive. However, the question
of whether caring can be effectively conveyed in online nursing classroom
settings remains unanswered. This qualitative study explored the perceptions of
one cohort of RN to BSN students regarding how instructors convey caring in
online education. Thirteen students were emailed surveys consisting of eight open
ended questions; II students responded. Eight themes emerged from the data:
frequent feedback, timeliness, reciprocity of caring online, personal connection
and empathy, clarity, multiple contact opportunities, second-fiddle worries, and
teacher's commitment to learning.
PMID- 17036684
TI - Assessing the critical thinking skills of faculty: What do the findings mean for
nursing education?
AB - The purpose of this study was twofold: to determine the critical thinking skills
of nurse faculty and to examine the relationship between epistemological position
and critical thinking. Most participants reported having no education on critical
thinking. Data were collected using the California Critical Thinking Skills Test
(CCTST) and the Learning Environment Preferences (LEP). Findings from the CCTST
indicated that faculty varied considerably in their ability to think critically;
LEP findings suggested that participants had not reached the intellectual level
needed for critical thinking. In addition, 12 faculty participated in one-hour
telephone interviews in which they described experiences in which students
demonstrated critical thinking. Despite a lack of clarity on the definition of
critical thinking, faculty described clinical examples where students engaged in
analysis, inference, and evaluation. Based on these findings, it is recommended
that faculty transfer their ability to engage students in critical thinking in
the clinical setting to the classroom setting. Benchmarks can be established
based on the ability of faculty to engage in critical thinking.
PMID- 17036685
TI - The evaluation of students' reflective writing for evidence of critical thinking.
AB - The purpose of this study was to establish interrater reliability of the Critical
Thinking Scale (CTS), a teacher-accessible tool designed to measure the critical
thinking of baccalaureate nursing students as evidenced in their reflective
writing about their practice experiences.The study is an extension of an earlier
pilot test of the CTS. Graduating students from a nursing program at a small
liberal arts college were asked to write about a significant practice experience
encountered during their last clinical course. Three teachers used the CTS to
independently evaluate the students' writing. California Critical Thinking Skills
Test (CCTST) scores provided a standard measure of critical thinking. Results
indicated statistically significant positive relationships between the CCTST
total critical thinking score and mean teacher ratings using the CTS.
Meaningfully significant interrater reliability ratings for the CTS were also
found. With further development, the CTS has promise as an appropriate tool to
evaluate students' reflective writing for evidence of critical thinking.
PMID- 17036686
TI - Got large lecture hall classes? Use clickers.
PMID- 17036688
TI - A nurse's camaraderie, Compassion, and service in Iraq.
PMID- 17036687
TI - Executive summary from the Nursing Data Review, Academic Year 2004-2005,
Baccalaureate, associate degree, and diploma programs.
PMID- 17036689
TI - Doctor's revenge.
PMID- 17036690
TI - Mumps, branks and other impediments.
PMID- 17036691
TI - Medical education at Brown Medical School.
PMID- 17036692
TI - The Brown Medical School Class of 2006.
PMID- 17036693
TI - Doctoring: clinical skills teaching in the 21st century.
PMID- 17036694
TI - So what the heck is an AHEC and what does it mean for Brown?
PMID- 17036695
TI - Education to improve interdisciplinary practice of health care professionals: a
pilot project.
PMID- 17036696
TI - The humble fly: what a model system can reveal about the human biology of aging.
PMID- 17036697
TI - Science and technology studies: its relevance to medical education and the
practice of medicine.
PMID- 17036698
TI - The health of Rhode Island's hospitals.
PMID- 17036699
TI - New prompt payment regulation offers greater protections to physicians.
PMID- 17036700
TI - The words of dermatology.
PMID- 17036701
TI - Healthcare industry representatives: maximizing benefits and reducing risks.
PMID- 17036702
TI - The oral/systemic connection: where's ECC? What's our role?
PMID- 17036703
TI - Comparison of mineral trioxide aggregate and calcium hydroxide as pulpotomy
agents in young permanent teeth (apexogenesis).
AB - PURPOSE: The purpose of this study was to compare mineral trioxide aggregate
(MTA) with calcium hydroxide (Ca(OH)2) clinically and radiographically as a
pulpotomy agent in immature permanent teeth (apexogenesis). METHODS: Fifteen
children, each with at least 2 immature permanent teeth requiring pulpotomy
(apexogenesis), were selected for this study. All selected teeth were evenly
divided into 2 test groups. In group 1, the conventional Ca(OH)2pulpotomy
(control) was performed, whereas in group 2, the MTA pulpotomy (experimental) was
done. The children were recalled for clinical and radiographic evaluations after
3, 6, and 12 months. RESULTS: The follow-up evaluations revealed failure due to
pain and swelling detected at 6 and 12 months postoperative evaluations in only 2
teeth treated with Ca(OH)2. The remaining 28 teeth appeared to be clinically and
radiographically successful 12 months postoperatively. Calcific metamorphosis was
a radiographic finding in 2 teeth treated with Ca(OH)2 and 4 teeth treated with
MTA. CONCLUSIONS: Mineral trioxide aggregate showed clinical and radiographic
success as a pulpotomy agent in immature permanent teeth (apexogenesis) and seems
to be a suitable alternative to calcium hydroxide.
PMID- 17036704
TI - Acute ethanol toxicity from ingesting mouthwash in children younger than age 6,
1989-2003.
AB - PURPOSE: The purpose of this study was to analyze American Association of Poison
Control Centers (AAPCC) reports of suspected overingestion of mouthwash by
children under age 6 and examine the effect of a 1995 Consumer Product Safety
Commission (CPSC) rule requiring child-resistant packaging for mouthwashes
containing at least 3 g (0.11 oz) of ethanol per package. METHODS: The volume of
ethanol ingested per kg of body weight was computed for children at the 5th,
50th, and 95th percentiles. The potentially toxic and potentially lethal volumes
of 100% ethanol at each weight were also determined. The authors used segmented
regression to test the difference in slopes between 1989 to 1996
(preintervention) and 1996 to 2003 (postintervention). RESULTS: Incidence of
overingestion rose from a low of 12.7 per 100,000 (1991) to 20.7 (1996). The
increase ended with the adoption of the CPSC rule, declining to 16.8 per 100,000
in 2001 and rising to 17.9 in 2003. CONCLUSIONS: This study's analysis suggests
that the CPSC rule requiring child-resistant packaging on containers of mouthwash
containing 3 g or more of ethanol has been successful in reducing AAPCC's reports
of mouthwash overingestion. Health care providers should take a more active role
by informing parents of the dangers associated with accidental ingestion of
ethanol-containing mouthwash. Manufacturers should print warnings about the
potential hazard of high ethanol concentrations on labels more prominent and they
should stop producing mouthwashes with such high concentrations of ethanol.
Moreover, they should also consider discontinuing packaging mouthwash in large
containers.
PMID- 17036705
TI - Supragingival calculus in children with gastrostomy feeding: significant
reduction with a caregiver-applied tartar-control dentifrice.
AB - PURPOSE: This study assessed the anti-calculus benefit of Crest Dual Action
Whitening Toothpaste in gastrostomy (GT) children compared to a control anti
caries dentifrice. METHODS: A double-blind randomized crossover design was used
to compare the two dentifrices. A convenience sample of 24 GT subjects, 3-12
years old, was given a consensus baseline Volpe-Manhold Index calculus score by 2
trained examiners, followed by a dental prophylaxis to remove all calculus. Each
child was randomly assigned to either study or control dentifrice groups.
Caregivers brushed subjects' teeth twice daily with the unlabelled dentifrice for
at least 45 seconds. Calculus was scored at 8 weeks (+/- 1 week) by the same
investigators. Subjects then had a prophylaxis and received the alternative
dentifrice. Subjects returned 8 weeks (+/- 1 week) later for final calculus
scoring. RESULTS: The study dentifrice significantly reduced supragingival
calculus from baseline by 58% compared to control dentifrice (p<0.005 need exact
p-value unless it is <.001; maybe it's reported in the paper). Calculus levels
decreased by 68% over the study duration, irrespective of dentifrice. ANOVA found
no significant differences in calculus scores based on gender, race, history of
reflux, aspiration pneumonia, or oral intake of food. Calculus was significantly
related to history of aspiration pneumonia (p<0.05 need exact p-value here).
CONCLUSION: Crest Dual Action Whitening Toothpaste was effective and better than
anti-caries control dentifrice in reducing calculus in GT children.
PMID- 17036706
TI - A cross-sectional study of medication-related factors and caries experience in
asthmatic children.
AB - PURPOSE: The purpose of this study was to examine the relationship between the
specific types of medication, length of use, frequency of use, and dosing time of
day on the dental caries of children diagnosed with asthma. METHODS: Using a
patient list from a previous study, surveys were mailed to the parents of 179
asthmatic children. The survey itself consisted of a table that asked 4
questions: (1) What combination of asthma medications was used by the subject?
(2) How long were the medications used? (3) How often were the medications used?
(4) What time of day were the medications used? RESULTS: Of the 179 surveys that
were mailed out, 156 were returned. Children who used their medication greater
than twice daily were significantly more likely to experience dental disease in
both the primary (odds ratio [OR]=2.56, 95% confidence interval [CI]=1.45-6.29)
and mixed dentitions (OR=3.56, 95% CI 2.45-5.94). CONCLUSIONS: Increased
frequency of asthma medication use was associated with increased likelihood of
caries experience. The time of day asthma medication was used was associated with
increased likelihood of caries experience in children in the primary dentition.
Duration of asthma medication use was associated with a decreased likelihood of
caries experience in children in the mixed dentition.
PMID- 17036707
TI - Evaluation of initial caries score and caries incidence in a public health
sealant program: a retrospective study.
AB - PURPOSE: The purpose of this study was to investigate the relationship between:
(1) children's caries score (dmft, DMFT) at the time of sealant placement; and
(2) "success" (measured as being caries-free) of that tooth at follow-up visits.
METHODS: An existing database of over 38,000 sealants (10,038 children) placed
between 1997 and 2002 by the Jefferson County Health Department's Community Based
Sealant Program, Birmingham, Ala, was used in the analysis. Only children
returning for followup visits after the initial placement of the sealants were
included in this study, resulting in 6,452 sealants (2,097 children). Logistic
regression analysis was performed to determine the differences in sealant success
between children with a dmft score of 0 vs a dmft score of >0 at baseline, and a
DMFT score of 0 vs a DMFT score of >0 at baseline. RESULTS: In the permanent and
primary dentitions, those who had no caries at the time of sealant placement
(dmft/DMFT=0) had a significantly higher success of sealants during years 1 to 5
compared to those with a caries score of greater than 0 (dmft/DMFT>0; P<.023,
P<.002, respectively). CONCLUSION: Children with previous caries experience may
be at a higher risk for sealant "failure" (measured as caries on a tooth surface
previously sealed) after 1 year and, therefore, may require more diligent sealant
maintenance.
PMID- 17036708
TI - Demographics and quality profile of applicants to pediatric dentistry
residencies.
AB - PURPOSE: The purpose of this study was to use Postdoctoral Application Support
Service (PASS) data to study the quality and demographic trends for pediatric
dentistry residency applicants. METHODS: PASS data on grade point average (GPA)
and National Dental Board Exam, Part I (NBI) scores were used to determine
applicant quality. PASS demographic data included: (1) gender; (2) citizenship;
(3) ethnicity; (4) previous practice of dentistry; and (5) completion of a
residency or internship. RESULTS: GPAs showed a significant increase for the 6
years investigated. NBI scores also indicated a significant increase.
Significantly more females than males applied to pediatric dentistry residencies.
A significant increase in US/Canadian applicants was found. Ethnicity was similar
to that of dental school graduates, with minor exceptions. In several of the
years studied, there were significant differences in applicants who previously
practiced dentistry or completed a residency/internship vs applicants who had no
such previous experience. CONCLUSIONS: Significant increases in grade point
averages and National Dental Board Exam, Part I scores suggest a high quality of
pediatric dentistry residency applicants and this trend seem to be continuing.
There are significantly more female than male applicants. More research is
warranted on actual acceptance data.
PMID- 17036709
TI - Experience and policy implications of children presenting with dental emergencies
to US pediatric dentistry training programs.
AB - PURPOSE: The purpose of this study was to describe and substantiate the
experience of children, their families, and their caregivers with children's
dental pain and to explore implications of these experiences for public policy.
METHODS: Data for 301 children presenting to 35 pediatric dentistry training
programs during a 1-week period in 2000 for pain relief were collected with a
questionnaire asking for: (1) sociodemographic characteristics; (2) oral health
status; (3) dental care history; (4) presenting problem; (5) clinical findings;
and (6) clinical disposition. Descriptive statistics are presented. RESULTS:
Among children presenting to training programs with oral pain, 28% were under age
6, 57% were on Medicaid, and 38% were regarded by their dentists to have "likely
or obvious" functional impairment-with 22% reporting the highest pain level.
Parents reported that 59% had "poor or fair oral health" and 29% had a prior
dental emergency in the previous year. Pain, experienced for several days by 73%
of children, was associated with difficulty: (1) eating; (2) sleeping; (3)
attending school; and (4) playing. Parent-reported barriers to seeking dental
care included: (1) missed work (24%); (2) transportation costs (12%); and (3)
arranging child care (10%). CONCLUSION: In this study of children with dental
pain, many suffered significant pain: (1) duration; (2) intensity; (3)
recurrence; and (4) consequences. This study demonstrates the ongoing need for
public policies that assure timely, comprehensive, and affordable dental care for
vulnerable children.
PMID- 17036710
TI - Knowledge and professional experiences concerning child abuse: an analysis of
provider and student responses.
AB - PURPOSE: The objective of this study was to explore dentists', dental
hygienists', dental students', and dental hygiene students' knowledge about their
professional responsibilities concerning suspected child abuse and their
professional experiences with this issue. METHODS: Questionnaire data were
collected from 220 general dentists, 158 dental hygienists, 233 dental, and 76
dental hygiene students regarding their knowledge, professional responsibilities,
and behavior concerning child abuse. RESULTS: Twenty percent of the dentists and
9% of the dental hygienists had reported at least 1 case of suspected child
abuse. While 83% of the dental professionals knew that they had to report
suspected cases of child abuse, only 73% of the students knew their legal
responsibility. Also, only 28% of the professionals and 18% of the students knew
where to report suspected child abuse. Compared to students, professionals had
more knowledge concerning the diagnosis of child abuse, while students were more
knowledgeable concerning signs of sexual abuse. Professionals, however, were less
likely to know that failure to report suspected abuse was a misdemeanor.
CONCLUSION: These data showed that not all dental care providers and students
were prepared to fulfill their legal and professional responsibilities in these
situations.
PMID- 17036711
TI - An in vitro evaluation of the effect of sealant characteristics on laser
fluorescence for caries detection.
AB - PURPOSE: The purposes of this study were to: (1) evaluate the ability of a laser
fluorescence (LF) unit to detect simulated caries under pit and fissure sealants;
(2) determine the effect of an opacifying agent in sealants on LF values; and (3)
determine interexaminer reproducibility values of the unit in a highly
controlled, laboratory setting. Sealant characteristics specifically considered
were: (1) filler content; (2) opacity; and (3) intrinsic fluorescence. METHODS:
Three sealants were used in this study: 2 unfilled and 1 filled. To evaluate the
effect of an opacifying agent, titanium dioxide powder was added to both filled
and unfilled sealants. 0.5-mm thick sealant discs were prepared for all samples.
The sealant discs were individually placed on top of 3 wells filled with varying
amounts of protoporphyrin IX, a fluorescent material that mimicked dental caries.
A total of 270 readings were made through the different sealant discs to evaluate
signal attenuation of the laser fluorescence unit. RESULTS: Clear sealants,
without an added opacifying agent, attenuated LF readings. At baseline
protoporphyrin IX levels yielding DIAGNOdent readouts of 20 and 60, there was a
significant difference in the LF readings between the baseline protoporphyrin
(uncovered) and with sealant disc covered in all 3 sealant types (P<.001).
Furthermore, the filled sealant attenuated LF signals significantly more than the
unfilled sealant (P<.001). Sealants with titanium dioxide added had variable
levels of intrinsic fluorescence. Titanium dioxide added to the sealants also had
a profound effect on fluorescence transmission of the underlying simulated
caries. As the concentration of titanium dioxide approached 0.5%, the
fluorescence signal was almost fully attenuated. CONCLUSION: Clinical detection
of caries under dental sealants with the use of laser fluorescence units is
unreliable and not recommended due to a high likelihood of inaccurate readings
caused by: (1) intrinsic fluorescence of sealant material; and (2) attenuation of
fluorescence signals by the sealant.
PMID- 17036713
TI - Engaging children's cooperation in the dental environment through effective
communication.
AB - Establishing a trusting relationship with the child patient is a critical
requisite for the pediatric dentist in gaining the child's cooperation in the
provision of oral health care. Developing such a relationship is predicated on
the establishment of effective communication. Many publications in the
psychological literature, specifically the parenting literature, describe
communication skills that are relevant to the pediatric dentist in effectively
communicating with children in the dental environment. Yet, several of these
approaches to communication are not generally discussed or advocated in the
dental literature. Among these skills are: (1) reflective listening; (2) self
disclosing assertiveness; and (3) the use of descriptive praise. This article:
(1) reviews these 3 skills; (2) describes their theoretical foundations; (3)
provides examples of when they are useful in the dentist-child clinical
encounter; and (4) indicates why they are important aspects of the pediatric
dentist's communication repertoire in establishing a positive, empathetic, and
mutually cooperative relationship with the child patient.
PMID- 17036712
TI - Effect of the calibration method of a laser fluorescence device for detecting
occlusal caries in primary molars.
AB - PURPOSE: The purpose of this study was to verify the influence of individual
calibration on sound tooth surfaces and the number of readings on in vitro
performance of a laser fluorescence (LF) device to detect occlusal caries in
primary teeth. METHODS: After standard calibration (on the porcelain reference
object), 72 clinically suspect sites on occlusal surfaces of 54 exfoliated or
extracted (for orthodontic purposes) primary molars were assessed using the
DIAGNOdent. First, after individual calibration (on a sound surface of each
tooth), 3 readings were performed for each site. Subsequently, another 3 readings
were taken, but without individual calibration on a sound surface of the tooth.
After these assessments, sites were also evaluated with only one reading after
individual calibration. Histological validation was performed as the gold
standard. LF values, sensitivity, specificity, accuracy (number of correct
diagnosis in both sound and diseased teeth) were calculated and compared using
the McNemar change test. The area under receiver operating characteristics (ROC)
curves was also compared. RESULTS: Readings with standard calibration only (mean=
11.7 +/- 10.6 SD) were significantly higher statistically than assessment with 3
readings after individual calibration (10.7 +/- 10.7) and with 1 reading (10.2 +/
8.3) after individual calibration. Nevertheless, sensitivity, specificity,
accuracy, and area under ROC curve did not change significantly. CONCLUSION:
Absence of individual calibration does not affect the laser fluorescence device's
performance in detecting occlusal caries in primary teeth.
PMID- 17036714
TI - Central hemangioma: an overview and case report.
AB - Central hemangioma of the mandible and maxilla is extremely rare. Although the
mucosal and soft tissue lesions are readily suspected by their clinical
appearance, the intrabony lesions may be difficult to distinguish visually. The
clinical and radiographic presentation is relatively nonspecific; therefore, a
proper diagnosis has to be made. The management of central hemangioma is
difficult because of the abundant vascular network in this region. Various
therapies have been considered, but surgery has most frequently been used. A case
report of an 8-year old boy with central hemangioma of the left mandibular body
with vague clinical features but a characteristic radiographic and histological
picture of central hemangioma is presented here. Also presented is a literature
review that includes: (1) clinical features; (2) radiographic appearance; (3)
histology; and (4) possible treatment modalities. Enbloc resection of the
mandible was performed, followed by the insertion of a reconstruction plate,
which will later be replaced by an autogenous graft.
PMID- 17036715
TI - Changing face of Medicare. As the popular administrator prepares to make his
exit, providers shouldn't expect much change in direction by his replacement.
AB - With Mark McClellan poised to exit the CMS, names of possible successors are
already being floated in Washington, including CMS executive Herb Kuhn, left.
Observers say whoever takes the job will face some tough challenges, and they
don't expect much policy to change with Bush still in the White House. "We will
continue to see what has effectively been gridlock" on many major healthcare
issues, one said.
PMID- 17036717
TI - Five years later...9/11 anniversary reveals industry's shortcomings.
PMID- 17036716
TI - GAO blasts HHS on IT, privacy. But exec argues before there can be 'detailed
plans', ONCHIT needs a leader.
PMID- 17036718
TI - Minn. talks universal care.
PMID- 17036719
TI - Pensions in peril? Law will spur switch to 401(k)-type plans: unions.
PMID- 17036720
TI - Healthcare insecurity. With voters worried about access, it shouldn't be
political business as usual.
PMID- 17036721
TI - Rocky Mountain low. Demise of a provider-owned, Medicaid managed-care plan is
national harbinger.
PMID- 17036722
TI - Dealing direct. Private placements--still just a fraction of the debt market-
have grown more popular by offering providers speed, flexibility.
PMID- 17036723
TI - Weighty concerns. Bariatric surgery programs on the rebound after initial
complications.
PMID- 17036724
TI - Residents still overworked? Studies' findings show polar-opposite conclusions.
PMID- 17036725
TI - Imclone's next headache.
PMID- 17036726
TI - Physician, fool thyself. Why the healing power of placebos is making doctors
think twice.
PMID- 17036728
TI - Bets on biotech. The nonprofit world steps in to finance for-profit drug
ventures.
PMID- 17036727
TI - The power of philanthropy.
PMID- 17036729
TI - Who pays for special ed?
PMID- 17036730
TI - A mothers choice.
PMID- 17036731
TI - Can we keep quality care alive?
PMID- 17036732
TI - Registered post.
AB - The professional work of nurses and doctors is subject to a rigorous statutory
regime of scrutiny. A pilot scheme in Scotland will shortly test out a new
register for healthcare support workers.
PMID- 17036733
TI - Being honest.
AB - Integrity means adhering to high moral principles or professional standards, but
there are barriers to achieving and maintaining it in nursing.
PMID- 17036734
TI - Your golden years.
PMID- 17036735
TI - Getting on with patients.
PMID- 17036736
TI - Stand up to the bullies.
PMID- 17036737
TI - More than a feeling.
PMID- 17036738
TI - Satisfaction guaranteed.
PMID- 17036739
TI - Spatial requirements in hospital shower and toilet rooms.
AB - AIM: To determine the spatial requirements for hoist use in an assisted shower
toilet facility. METHOD: A simulation of two shower-toilet facilities (built
since 2000) was constructed in a laboratory to compare a mobile hoist and a
gantry (overhead) hoist for the task of transferring a patient from a wheelchair
to the toilet. Twenty participants were recruited and trained in the use of both
hoists. Data were recorded using video cameras and analysed for the space used to
complete the task, time taken and postural risk scores. RESULTS: The mobile hoist
needed significantly more space, took significantly longer and exposed the
handlers to higher postural risks than the overhead hoist. CONCLUSION: Larger
shower-toilet rooms should be planned and built as accessible facilities with
sufficient space for independent and assisted wheelchair users. The findings will
have an impact on the recommendation for increased numbers of single rooms with
ensuite facilities in new hospitals. Healthcare planners and designers may need
to consider building specific facilities for assisted wheelchair users rather
than providing a 'one space fits all' solution.
PMID- 17036740
TI - Barriers to effective nutritional care for older adults.
AB - This article reviews the relationship between ageing and nutrition. The
vulnerability of older adults to nutritional decline is explored and the
importance of nutritional screening in this population is discussed. The author
considers some of the barriers to achieving nutritional adequacy once patients
have been admitted to hospital and suggests how these can be overcome.
PMID- 17036741
TI - The role of carbohydrates in a healthy diet.
AB - Nurses have an important role to play in improving patients' diets. This article
examines the role of carbohydrates in the prevention and management of disease.
It discusses the qlycaemic response and index, the importance of fibre, insulin
sensitivity, weight management and the role of resistant starch in healthy
eating.
PMID- 17036742
TI - Venepuncture.
PMID- 17036743
TI - Aide to recovery.
PMID- 17036744
TI - Statistical analysis of test-day milk yields using random regression models for
the comparison of feeding groups during the lactation period.
AB - Random regression models are widely used in the field of animal breeding for the
genetic evaluation of daily milk yields from different test days. These models
are capable of handling different environmental effects on the respective test
day, and they describe the characteristics of the course of the lactation period
by using suitable covariates with fixed and random regression coefficients. As
the numerically expensive estimation of parameters is already part of advanced
computer software, modifications of random regression models will considerably
grow in importance for statistical evaluations of nutrition and behaviour
experiments with animals. Random regression models belong to the large class of
linear mixed models. Thus, when choosing a model, or more precisely, when
selecting a suitable covariance structure of the random effects, the information
criteria of Akaike and Schwarz can be used. In this study, the fitting of random
regression models for a statistical analysis of a feeding experiment with dairy
cows is illustrated under application of the program package SAS. For each of the
feeding groups, lactation curves modelled by covariates with fixed regression
coefficients are estimated simultaneously. With the help of the fixed regression
coefficients, differences between the groups are estimated and then tested for
significance. The covariance structure of the random and subject-specific effects
and the serial correlation matrix are selected by using information criteria and
by estimating correlations between repeated measurements. For the verification of
the selected model and the alternative models, mean values and standard
deviations estimated with ordinary least square residuals are used.
PMID- 17036745
TI - Different effects of difructose anhydride III and inulin-type fructans on caecal
microbiota in rats.
AB - The effects of different kinds of inulin-type fructans on caecal microbiota were
evaluated in rats. Four groups of male Wistar rats were fed either a control
diet, or diets containing 5% inulin, 5% fructooligosaccharides (FOS), or 5%
difructose anhydride III (DFAIII) for two weeks. In the DFAIII group, caecal
propionate, butyrate, counts of bifidobacteria, and total anaerobes were lower
than in the inulin group, while caecal propionate, succinate, counts of
bifidobacteria, and total anaerobes were lower than in the FOS group. Compared to
controls, in the DFAIII group the counts of clostridia in caecum were increased
by 3 log units. However, this change was statistically not significant. There
were no differences between inulin and FOS groups for the pool of short chain
fatty acids in caecum and bacterial counts. Results indicate that DFAIII has
different effects on caecal microbiota compared to inulin and FOS and that these
differences are most likely due to the alpha(3-->2) bonds in DFAIII.
PMID- 17036746
TI - Effect of bacterial protein meal on protein and energy metabolism in growing
chickens.
AB - This experiment investigates the effect of increasing the dietary content of
bacterial protein meal (BPM) on the protein and energy metabolism, and carcass
chemical composition of growing chickens. Seventy-two Ross male chickens were
allocated to four diets, each in three replicates with 0% (D0), 2% (D2), 4% (D4),
and 6% BPM (D6), BPM providing up to 20% of total dietary N. Five balance
experiments were conducted when the chickens were 3-7, 10-14, 17-21, 23-27, and
30-34 days old. During the same periods, 22-h respiration experiments (indirect
calorimetry) were performed with groups of 6 chickens (period 1), 5 chickens
(period 2), and one chicken (periods 3-5). After each balance period, one chicken
in each cage was killed and the carcass weight was recorded. Chemical analyses
were performed on the carcasses from periods 1, 3, and 5. Weight gain, feed
intake, and feed conversion rate were found to be similar for all diets. Chickens
on D0 retained 1.59 g N x kg(-0.75) x d(-1), significantly more than chickens on
D2, D4, and D6, which retained 1.44 g, 1.52 g, and 1.50 g N x kg(-0.75) x d(-1),
respectively. This was probably caused by the higher nitrogen content of DO.
Neither the HE (p = 0.92) nor the retention of energy (p = 0.88) were affected by
diet. Carcass composition was similar between diets, in line with the values for
protein and energy retention found in the balance and respiration experiments. It
was concluded that the overall protein and energy metabolism as well as carcass
composition were not influenced by a dietary content of up to 6% BPM
corresponding to 20% of dietary N.
PMID- 17036747
TI - Influence of benzoic acid and dietary protein level on performance, nitrogen
metabolism and urinary pH in growing-finishing pigs.
AB - An experiment was conducted to examine the effect of benzoic acid and two dietary
protein levels on pig performance, nitrogen balance and urinary pH. A total of 24
crossbred barrows (26 kg to 106 kg BW) received one of four diets: low protein
level with and without 1% benzoic acid (LP- and LP+, respectively) and high
protein level with and without 1% benzoic acid (HP- and HP+, respectively). The
animals were fed restrictively grower and finisher diets and were kept in
metabolic cages in weeks 3, 6, 9, and 12 of the experiment. The addition of
benzoic acid did not improve weight gain and feed conversion ratio. N-intake and
digested N were only influenced by dietary protein level (p< 0.01), while N
balance was similar in all four diets. Dietary benzoic acid improved N
digestibility in the grower period (p<0.01) but not in the finisher period. The
addition of benzoic acid reduced urinary pH by about one pH-unit in both feeding
periods independent of the protein level of the diet (p< 0.01) and increased the
concentration of urinary hippuric acid markedly (p<0.01). The results of this
study indicate a positive influence of dietary benzoic acid on pigs especially in
case of feeding a low protein diet in the grower period.
PMID- 17036748
TI - Influence of different fibre sources on digestibility and nitrogen and energy
balances in growing pigs.
AB - The present study was undertaken to investigate how three different fibre
sources, sugar beet pulp, soya bean hulls and pectin residue, constituting 15% of
diets for growing pigs, influenced daily body gain, feed conversion, apparent
faecal digestibility and nitrogen and energy balances. Eight castrated crossbreed
pigs (30-80 kg live weight) were used in a replicated 4 x 4 Latin-square design
with one control diet and three fibre containing diets. Daily body weight gain
and feed conversion were not affected by the dietary treatments. The apparent
faecal digestibility of organic matter (OM) and energy were significantly lower
for the fibre diets (OM: 0.81-0.85; energy: 0.78-0.83) compared to the control
diet (OM: 0.88; energy: 0.86). The apparent faecal digestibility of crude protein
(CP) was lower for the fibre diets (0.71-0.78) compared to the control diet
(0.83), although it was only significantly lower for the sugar beet pulp and
pectin residue diets. The pectin residue diet, which contained the highest amount
of dietary fibre, lignin and insoluble non-starch polysaccharides, had the lowest
digestibility of OM, CP and energy. There was a tendency (p = 0.07) for a diet
effect on retained nitrogen in proportion to digested nitrogen, where the sugar
beet pulp and pectin residue diets had numerically the highest values. Heat
production and retained energy in proportion to metabolizable energy intake were
not affected by fibre inclusion. It was concluded that the inclusion of sugar
beet pulp, soya bean hulls and pectin residue in diets for growing pigs decreased
the apparent faecal digestibility and in the diets with sugar beet pulp and
pectin residue higher utilization of digested nitrogen for retention compensated
for the lower amount of digested nitrogen.
PMID- 17036749
TI - Effect of different types of fibre supplemented with sunflower oil on ruminal
fermentation and production of conjugated linoleic acids in vitro.
AB - An in vitro study was conducted to determine the effect of different types of
fibre supplemented with sunflower oil on ruminal fermentation and formation of
conjugated linoleic acids (CLA) by mixed ruminal microorganisms. Cell wall
components extracted from wheat straw (representing lignified fibre), soybean
hulls (representing easily digestible fibre), and purified cellulose were used as
substrates. Sunflower oil was supplemented at the same level for all three types
of fibre. After 24 h of incubation, ruminal fermentation parameters (including 24
h gas production, pH value, concentration of ammonia nitrogen and volatile fatty
acids) and the concentration of long chain fatty acids in the culture fluid were
determined. Results showed that the type of fibre influenced ruminal fermentation
traits and the biohydrogenation of unsaturated C18 fatty acids in vitro.
Composition of LCFA and profile of CLA were altered by the fibre type. Compared
to the digestible fibre and purified cellulose, lignified fibre significantly
increased the production of cis-9, trans-11 CLA and total CLA (sum of cis-9,
trans-11 CLA, trans-10, cis-12 CLA, trans-9, trans-11 CLA, and cis-9, cis-11 CLA)
by ruminal microorganisms. It was concluded that ruminal fermentation and
production of CLA can be affected by the type of dietary fibre.
PMID- 17036750
TI - In vitro degradation of wheat straw by anaerobic fungi from small ruminants.
AB - Anaerobic ruminal fungi may play an active role in fibre degradation as evidenced
by the production of different fibrolytic enzymes in culture filtrate. In the
present study, 16 anaerobic fungal strains were isolated from ruminal and faecal
samples of sheep and goats. Based on their morphological characteristics they
were identified as species of Anaeromyces, Orpinomyces, Piromyces and
Neocallimastix. Isolated Neocallimastix sp. from goat rumen showed a maximum
activity of CMCase (47.9 mIU ml(-1)) and filter paper cellulase (48.3 mIU ml(
1)), while Anaeromyces sp. from sheep rumen showed a maximum xylanolytic activity
(48.3 mIU ml(-1)). The cellobiase activity for all the isolates ranged from 178.0
182.7 mIU ml(-1). Based on the enzymatic activities, isolated Anaeromyces sp.
from sheep rumen and Neocallimastix sp. from goat rumen were selected for their
potential of in vitro fibre degradation. The highest in vitro digestibility of
NDF (23.2%) and DM (34.4%) was shown for Neocallimastix sp. from goat rumen, as
compared to the digestibility of NDF and DM in the control group of 17.5 and
25.0%, respectively.
PMID- 17036751
TI - Effects of purified soybean agglutinin on growth and immune function in rats.
AB - The objective of this study was to investigate the effect of purified soybean
agglutinin on growth and immune function in rats. Thirty male Sprague-Dawley rats
(77.8 +/- 2.6 g) were individually fed casein-cornstarch based diets containing
0, 0.05, 0.10, 0.15 or 0.20% soybean agglutinin (w/w) during a 20-day experiment.
Growth declined linearly with increasing the concentration of soybean agglutinin
(p < 0.05). The proliferation of lymphocytes in spleen, lymph nodes and blood
decreased with an increase in dietary soybean agglutinin (p < 0.05). The
concentrations of interleukin-2, interferon-gamma and tumor necrosis factor-alpha
in plasma, spleen, and mesenteric lymph nodes as well as plasma concentrations of
IgA, IgG and IgM also declined with increasing dose of soybean agglutinin (p <
0.05). The results show that dietary soybean agglutinin has negative effects on
growth as well as both cell-mediated and humoral immune function of rats and
appears to function in a dose-dependent manner.
PMID- 17036752
TI - Effects of chicken intestinal antimicrobial peptides on humoral immunity of
chickens and antibody titres after vaccination with infectious bursal disease
virus vaccine in chicken.
AB - Sixty chickens were randomly divided into two groups (30 chickens in each group)
to determine the effect of oral administration of chicken intestinal
antimicrobial peptides (CIAMP) on the humoral immune response. Chickens of both
groups were fed the same diet. In the treatment group chickens received drinking
water supplemented with CIAMP (1 microg/ml) right after hatching. Samples of
blood, bursa of Fabricus, spleen and intestine were taken at day 1, 4, 7, 10 and
17 of experiment. CIAMP supplementation enhanced the content of IgG and IgM in
serum from day 4-10 and day 10-17, respectively, (p < 0.05), IgM-forming cells in
bursa of Fabricus and spleen at the age of 7 days (p < 0.05) and IgG-forming
cells in bursa of Fabricus at the age of 4 days (p < 0.05). In addition, CIAMP
enhanced the IgA-forming cells in caecal tonsils diffuse area at day 4 (p <
0.05). Furthermore, CIAMP enhanced the antibody response to infectious bursal
disease virus vaccine (IBDV) in chickens 21 days following IBDV vaccine
administration (p < 0.05). These results suggested that CIAMP could modulate the
humoral immune response of chickens and increased the antibody titres of
infectious bursal disease virus vaccine.
PMID- 17036753
TI - Efficacy of a herbal product against Histomonas meleagridis after experimental
infection of turkey poults.
AB - Histomoniasis (infectious enterohepatitis, blackhead) is caused by the protozoan
parasite Histomonas meleagridis (H. meleagridis). After the ban of all
prophylactic and therapeutic drugs in the European Union, histomoniasis is
increasingly responsible for considerable economic problems to the poultry
industry. The aim of this study was to investigate the effect of a herbal product
with extracts from cinnamon, garlic, lemon, and rosemary on H. meleagridis in
turkey poults in vivo. For this purpose, 60 two-week-old poults were divided into
three groups. Group 1 received the herbal product in the feed six days before
infection and in water three days before infection, then in feed and drinking
water until the end of the experiment. Groups 2 and 3 were left untreated. At
week 3 of age, Groups 1 and 2 were infected intracloacally with H. meleagridis.
Three weeks after infection the surviving birds were euthanized and examined for
pathological lesions. Mortality was 20% in Group 1 and 50% in Group 2. There were
no deaths in Group 3. DNA of histomonads was detected in all examined caeca and
livers of the dead birds, but was not detected in any examined organ of the
surviving birds of all groups. There was no noticeable difference in the lesion
scores of the dead birds between the groups. The surviving birds of all groups
did not show lesions post mortem. Since all effective prophylactic and
therapeutic drugs against histomoniasis were banned in the EU, under given
conditions the investigated herbal product seems to be an effective alternative
for the reduction of mortality in turkeys caused by histomoniasis.
PMID- 17036755
TI - Technology. IT gets HIPAA.
PMID- 17036756
TI - Finances. Payment makeover.
PMID- 17036757
TI - Governance. Minority report.
PMID- 17036758
TI - Nursing. Visas nearing cap.
PMID- 17036759
TI - Regulation. Thank you, IRS.
PMID- 17036760
TI - Regulation. 'Big deal' for EHRs.
PMID- 17036761
TI - Regulation. Make the transfer.
PMID- 17036762
TI - Data page. Physician use of EMRs is growing.
PMID- 17036763
TI - A living monument.
AB - This month marks the five-year anniversary of the Sept. 11 terrorist attacks.And
its been one year since two hurricanes ripped through the Gulf Coast. How can you
remember the heroes who gave so much of themselves during those tragic events? By
being one. Every day.
PMID- 17036764
TI - Save lives now. 30 things you can do to eliminate infections.
AB - More than 2 million Americans a year acquire infections during a hospital stay,
often with deadly results. These infections are costly to treat and difficult to
rationalize to patients and the public. And most of them can be prevented. Here
are 30 simple and low-cost things that you can do right now to eliminate
infections in your hospital. Well outline additional steps in upcoming issues of
H&HN as part of the 2006 Save Lives Now series.
PMID- 17036765
TI - Taking stock. Interview by Matthew Weinstock.
PMID- 17036766
TI - The American Hospital Association-McKesson Quest for Quality Prize 2006 winner.
Cincinnati Children's Hospital Medical Center. Aiming to be 'the best at getting
better'.
PMID- 17036767
TI - Stopping ED violence before it happens.
PMID- 17036768
TI - Collaboration Seattle style.
PMID- 17036769
TI - The future of voluntary governance.
PMID- 17036770
TI - Store-bought lessons.
PMID- 17036771
TI - Poised for growth. Point-of-care testing.
AB - The United States is the world's biggest market for diagnostic testing, and one
of the most active segments within that is point-of-care testing, or POCT. As
test devices become more compact and easier to use, as well as more accurate,
tests can be more frequently performed at the point of care, whether that is the
emergency department, intensive care unit or a patient's home. Among the most
common tests are those for blood glucose, blood gases, cardiac markers and
sepsis, as well as pregnancy and ovulation. The biggest advantage of POCT is
speed. Although home-based point-of-care testing is common, 70 percent of POCT
takes place in hospitals, doctor's offices and other provider locations, and
experts predict this segment will grow an average of 15.5 percent each year,
significantly outpacing home-based testing. This gatefold gives an overview of
POCT, discusses the challenges, benefits for hospitals, and provides a glimpse of
what experts believe point-of-care testing will look like in the future.
PMID- 17036772
TI - The future of the EHR. Connecting across the care continuum. An executive
dialogue on overcoming the obstacles to a national health information system.
PMID- 17036773
TI - Democracy is a team sport.
PMID- 17036774
TI - Artificial disc replacement: progress or hype?
PMID- 17036775
TI - Advances in osteobiologics in spine surgery.
AB - In spine surgery, fixation devices that revolutionized spinal fusion are becoming
mature technologies, and new tools derived from biologics are becoming more
important in clinical practice. Thus, surgeons need to become more sophisticated
in evaluating and using these new biologics, which are rapidly entering the
market. The majority of these biologics are aimed at enhancing spinal fusion and
can be called osteobiologics. Osteobiologic products vary from recombinant
proteins to specially prepared allograft or autograft materials. Their financial
costs are considerable, and the level of proof for the efficacy and safety of
these products varies widely. In this article, I delineate useful principles that
can be used to evaluate current and future generations of osteobiologic products,
and I discuss the most pertinent examples of specific osteobiologics.
PMID- 17036776
TI - Motion preservation technologies: alternatives to spinal fusion.
AB - Spinal arthrodesis is a versatile and effective option in the management of
instabilities, deformities, and painful spinal conditions. An increasing body of
biomechanical and clinical evidence suggests that the relative immobility of
fused spinal segments alters stress transfer, leading to adjacent-level
degeneration. The development of nonfusion spinal prostheses has been driven by
increasing concerns regarding these arthrodesis-related morbidities, including
graft-site harvest, pseudarthrosis, and adjacent-level degeneration. Motion
sparing implants offer some theoretical advantages over fusion; however,
judicious use of these products with careful patient selection is warranted until
outcome studies can demonstrate their efficacy. In this article, we review the 3
major categories of nonfusion technologies: total disc replacement, prosthetic
nuclear implants, and posterior stabilization devices.
PMID- 17036777
TI - Reimbursement essentials for the orthopedic practice.
PMID- 17036778
TI - Hyaluronans: is clinical effectiveness dependent on molecular weight?
AB - The original rationale for viscosupplementation with hyaluronans was fluid
replacement, suggesting that the most viscous materials (eg, those of highest
molecular weight [MW]) would provide the most clinical benefits. However, it has
become clear that mechanisms of action for osteoarthritis pain management are not
only mechanical but also biological. After intra-articular injection, hyaluronans
exert a range of biological actions within the joint. Although high- and low- to
mid-MW hyaluronans (but not hyaluronans <500 kDa MW) are more or less active
(depending on the specific effect examined), it is not known which actions are
clinically meaningful. There is no evidence for a difference between hyaluronan
products in clinical efficacy measured as pain relief, but investigators in
several preclinical studies evaluating joint-structure modification in
osteoarthritis models have reported advantages to using low- to mid-MW
hyaluronans.
PMID- 17036779
TI - Autologous hamstring anterior cruciate ligament reconstruction in patients older
than 40.
AB - The primary objective in this retrospective review was to assess the patient
specific outcomes and clinical utility of anterior cruciate ligament (ACL)
reconstruction using the autologous quadruple-band hamstring technique in
patients older than 40. Study results agree with the recent literature and
demonstrate the effectiveness of an alternative to the bone-patellar tendon-bone
(BPB) technique-an alternative with potentially decreased postoperative
morbidity. Results also support the recent conclusion that age alone should not
be a limiting factor in whether ACL reconstruction should be performed. We found
that appropriately selected patients may experience significant improvements in
stability, function, and pain after ACL reconstruction with the quadruple-band
hamstring autograft technique. For outcomes after ACL reconstruction, there seems
to be no significant difference between the sexes or between patients with and
without associated injuries in this population. This study also supports use of
the autologous hamstring technique as a viable option for older patients-with
results similar to those of the BPB technique. The autologous hamstring technique
was associated with excellent patient satisfaction and excellent functional
outcome with limited postoperative morbidity. This technique may become the
preferred approach for the older athlete, given its limited morbidity and
equivalent clinical stability.
PMID- 17036780
TI - A ring transducer system for medical ultrasound research.
AB - An ultrasonic ring transducer system has been developed for experimental studies
of scattering and imaging. The transducer consists of 2048 rectangular elements
with a 2.5-MHz center frequency, a 67% -6 dB bandwidth, and a 0.23-mm pitch
arranged in a 150-mm-diameter ring with a 25-mm elevation. At the center
frequency, the element size is 0.30lambda x 42lambda and the pitch is 0.38lambda.
The system has 128 parallel transmit channels, 16 parallel receive channels, a
2048:128 transmit multiplexer, a 2048:16 receive multiplexer, independently
programmable transmit waveforms with 8-bit resolution, and receive amplifiers
with time variable gain independently programmable over a 40-dB range. Receive
signals are sampled at 20 MHz with 12-bit resolution. Arbitrary transmit and
receive apertures can be synthesized. Calibration software minimizes system
nonidealities caused by noncircularity of the ring and element-to-element
response differences. Application software enables the system to be used by
specification of high-level parameters in control files from which low-level
hardware-dependent parameters are derived by specialized code. Use of the system
is illustrated by producing focused and steered beams, synthesizing a spatially
limited plane wave, measuring angular scattering, and forming b-scan images.
PMID- 17036781
TI - Performance and characterization of new micromachined high-frequency linear
arrays.
AB - A new approach for fabricating high frequency (> 20 MHz) linear array
transducers, based on laser micromachining, has been developed. A 30 MHz, 64
element, 74-microm pitch, linear array design is presented. The performance of
the device is demonstrated by comparing electrical and acoustic measurements with
analytical, equivalent circuit, and finite-element analysis (FEA) simulations.
All FEA results for array performance have been generated using one global set of
material parameters. Each fabricated array has been integrated onto a flex
circuit for ease of handling, and the flex has been integrated onto a custom
printed circuit board test card for ease of testing. For a fully assembled array,
with an acoustic lens, the center frequency was 28.7 MHz with a one-way -3 dB and
-6 dB bandwidth of 59% and 83%, respectively, and a -20 dB pulse width of -99 ns.
The per-element peak acoustic power, for a +/- 30 V single cycle pulse, measured
at the 10 mm focal length of the lens was 590 kPa with a -6 dB directivity span
of about 30 degrees. The worst-case total cross talk of the combined array and
flex assembly is for nearest neighboring elements and was measured to have an
average level -40 dB across the -6 dB bandwidth of the device. Any significant
deviation from simulation can be explained through limitations in apparatus
calibration and in device packaging.
PMID- 17036782
TI - Design of a multilayer transducer for acoustic bladder volume assessment.
AB - Catheterization remains the "gold standard" for bladder volume assessment, but it
is invasive and introduces the risk of infections and traumas. Therefore,
noninvasive bladder volume measurement methods have gained interest. In a
preceding study a new technique to measure the bladder volume on the basis of
nonlinear ultrasound wave propagation was validated. This paper describes a first
prototype of a dedicated multilayer transducer to implement this approach. It is
composed of a PZT transducer for transmission and a PVDF layer for reception.
Acoustical measurements in a water tank and phantom measurements showed that
there is a relation between bladder volume and the harmonic contents of the echo
obtained from a region of interest behind the bladder. Simulations with an
equivalent transducer model on the basis of KLM-circuit modeling closely matched
with the results from the acoustical measurements. The results demonstrated the
feasibility of the multilayer transducer design for bladder volume assessment on
the basis of nonlinear wave propagation.
PMID- 17036783
TI - Harmonic 3-D echocardiography with a fast-rotating ultrasound transducer.
AB - Although the advantages of three-dimensional (3-D) echocardiography have been
acknowledged, its application for routine diagnosis is still very limited. This
is mainly due to the relatively long acquisition time. Only recently has this
problem been addressed with the introduction of new real-time 3-D echo systems.
This paper describes the design, characteristics, and capabilities of an
alternative concept for rapid 3-D echocardiographic recordings. The presented
fast-rotating ultrasound (FRU)-transducer is based on a 64-element phased array
that rotates with a maximum speed of 8 Hz (480 rpm). The large bandwidth of the
FRU-transducer makes it highly suitable for tissue and contrast harmonic imaging.
The transducer presents itself as a conventional phased-array transducer;
therefore, it is easily implemented on existing 2-D echo systems, without
additional interfacing. The capabilities of the FRU-transducer are illustrated
with in-vitro volume measurements, harmonic imaging in combination with a
contrast agent, and a preliminary clinical study.
PMID- 17036784
TI - Noninvasive field measurement of low-frequency ultrasonic transducers operating
in sealed vessels.
AB - This paper describes a noninvasive technique utilizing the acousto-optic effect,
laser interferometry, and tomographic principles that have been implemented to
measure the acoustic fields generated by low-frequency ultrasonic transducers
operating into sealed, water-loaded vessels commonly used in industrial
processing applications. A customized scanning frame, incorporating both linear
and rotational stages, has been developed to facilitate manipulation of the laser
head and vessel under evaluation. First, transmitted pressure profiles in air are
predicted from surface displacement data acquired directly by laser measurement
of the vibrating aperture. These profiles were then used to verify the measured
fields obtained via conventional tomographic scanning procedures, coupled with
laser interferometry, applied within a draft-proof scanning facility under free
field conditions. Next, the finite element code PZF(lex) was employed for the
prediction of pressure fields within cylindrical cell configurations. Finally,
precise manipulation of the laser firing angle and position was implemented in
order to compensate for the effects of refraction at the cell wall boundaries,
and to re-establish the projections required for the reconstruction algorithm.
The experimental results demonstrate good corroboration with the PZF(lex)
predictions, validating its application of ultrasound as a virtual prototyping
tool for the design of high power ultrasonic test vessels.
PMID- 17036785
TI - An ultrasound research interface for a clinical system.
AB - Under a contract with the National Cancer Institute, we have developed a research
interface to an ultrasound system. This ultrasound research interface (URI) is an
optional feature providing several basic capabilities not normally available on a
clinical scanner. The URI can store high-quality beamformed radio-frequency data
to file for off-line processing. Also, through an integrated user interface, the
user is provided additional control over the B-mode receive aperture and color
flow ensemble size. A third major capability is the ability to record and
playback macro files. In this paper, we describe the URI and illustrate its use
on three research examples: elastography, computed tomography, and spatial
compounding.
PMID- 17036786
TI - The Ultrasonix 500RP: a commercial ultrasound research interface.
AB - Unlike researchers in magnetic resonance imaging who have considerable access to
high level tools and to data at a very basic level on their scanners, those
involved with ultrasound have found little in the way of meaningful and
widespread access to even the most basic echo signals in their clinical systems.
Interest has emerged, however, in ultrasound research interfaces on commercial
scanners to provide access to raw ultrasound data and control of basic research
functions. This paper describes initial experience gained on one such ultrasound
system. The Ultrasonix 500RP system provides research access to the data at
multiple points in the signal processing chain and allows control over most
imaging parameters. The Ultrasonix system allows for three methods of research
control. One is implemented along with the standard clinical imaging software
using "mouseover" screens on the periphery of the application window. These
screens are configured by the user to display various signal processing
variables, which can be modified in real time. Second, the system can be
controlled via a user-written remote control client application interacting
through the clinical exam software. Lastly, the user can write a complete
application which initializes the basic ultrasound module but need not use the
Ultrasonix clinical exam software. All of the modes can be done locally on the
scanner itself or via a network, and are based on software developed in C++ with
libraries supplied with the scanner. Two examples are presented in this paper
from the evaluation of the system in "real world" applications. Measurements of
absolute backscatter coefficients and attenuation coefficients versus frequency
are shown and elastograms utilizing spatial compounding are described.
PMID- 17036787
TI - FEMMINA real-time, radio-frequency echo-signal equipment for testing novel
investigation methods.
AB - Fast echographic multiparameter multi-image novel apparatus (FEMMINA), is a
hardware and software platform dedicated to ultrasonic signal and image
processing. FEMMINA is able to operate with sequences of radiofrequency (RF)
frames. Its architecture is designed to be modular, expandable, and aimed at
implementing different ultrasonic investigation techniques. The first
experimental characteristic of this system is in its capability to operate in
real time with ultrasonic RF signals, starting from acquisition up to processing,
storage, and visualization. The second characteristic is the user-system
interactivity that allows one to modify the operation appropriately while
observing results. Currently, FEMMINA works in both typical experimental
situations to study novel investigation techniques and clinical field to validate
the proposed methods in different human districts.
PMID- 17036788
TI - High frame rate imaging system for limited diffraction array beam imaging with
square-wave aperture weightings.
AB - A general-purpose high frame rate (HFR) medical imaging system has been
developed. This system has 128 independent linear transmitters, each of which is
capable of producing an arbitrary broadband (about 0.05-10 MHz) waveform of up to
+/- 144 V peak voltage on a 75-ohm resistive load using a 12-bit/40-MHz digital
to-analog converter. The system also has 128 independent, broadband (about 0.25
10 MHz), and time-variable-gain receiver channels, each of which has a 12-bit/40
MHz analog-to-digital converter and up to 512 MB of memory. The system is
controlled by a personal computer (PC), and radio frequency echo data of each
channel are transferred to the same PC via a standard USB 2.0 port for image
reconstructions. Using the HFR imaging system, we have developed a new limited
diffraction array beam imaging method with square-wave aperture voltage
weightings. With this method, in principle, only one or two transmitters are
required to excite a fully populated two-dimensional (2-D) array transducer to
achieve an equivalent dynamic focusing in both transmission and reception to
reconstruct a high-quality three-dimensional image without the need of the time
delays of traditional beam focusing and steering, potentially simplifying the
transmitter subsystem of an imager. To validate the method, for simplicity, 2-D
imaging experiments were performed using the system. In the in vitro experiment,
a custom-made, 128-element, 0.32-mm pitch, 3.5-MHz center frequency linear array
transducer with about 50% fractional bandwidth was used to reconstruct images of
an ATS 539 tissue-mimicking phantom at an axial distance of 130 mm with a field
of view of more than 90 degrees. In the in vivo experiment of a human heart,
images with a field of view of more than 90 degrees at 120-mm axial distance were
obtained with a 128-element, 2.5-MHz center frequency, 0.15-mm pitch Acuson V2
phased array. To ensure that the system was operated under the limits set by the
U.S. Food and Drug Administration, the mechanical index, thermal index, and
acoustic output were measured. Results show that higher-quality images can be
reconstructed with the square-wave aperture weighting method due to an increased
penetration depth as compared to the exact weighting method developed previously,
and a frame rate of 486 per second was achieved at a pulse repetition frequency
of about 5348 Hz for the human heart.
PMID- 17036789
TI - A programmable real-time system for development and test of new ultrasound
investigation methods.
AB - In vitro and/or in vivo experimental tests represent a crucial phase in the
development of new ultrasound (US) investigation methods for biomedical
applications. Such tests frequently are made difficult by the lack of flexibility
of general purpose instruments and commercial US machines typically available in
research laboratories. This paper presents a novel, real-time development system
specifically designed for US research purposes. Main features of the system are
the limited dimensions (it is based on a single electronic board), the capability
of transmitting arbitrary waveforms to two probes, of storing the received radio
frequency (RF) echo data in a file and/or of processing them in real-time
according to programmable algorithms. As an example of application, results of
simultaneous hemodynamic and mechanic investigations in human arteries are
reported. However, the high system flexibility and portability make it suitable
for a large class of US applications.
PMID- 17036790
TI - The progressive focusing correction technique for ultrasound beamforming.
AB - This work presents a novel method for digital ultrasound beamforming based on
programmable table look-ups, in which vectors containing coded focusing
information are efficiently stored, achieving an information density of a
fraction of bit per acquired sample. Timing errors at the foci are within half
the period of a master clock of arbitrarily high frequency to improve imaging
quality with low resource requirements. The technique is applicable with
conventional as well as with deltasigma converters. The bit-width of the focusing
code and the number of samples per focus can be defined to improve both memory
size and F# with controlled timing errors. In the static mode, the number of
samples per focus is fixed, and in the dynamic approach that figure grows
progressively, taking advantage of the increasing depth of focus. Furthermore,
the latter has the lowest memory requirements. The technique is well suited for
research purposes as well as for real-world applications, offering a degree of
freedom not available with other approaches. It allows, for example, modifying
the sampling instants to phase aberration correction, beamforming in layered
structures, etc. The described modular and scalable prototype has been built
using low-cost field programmable gate arrays (FPGAs). Experimental measurements
are in good agreement with the theoretically expected errors.
PMID- 17036791
TI - Adaptive imaging on a diagnostic ultrasound scanner at quasi real-time rates.
AB - Constructing an ultrasonic imaging system capable of compensating for phase
errors in real-time is a significant challenge in adaptive imaging. We present a
versatile adaptive imaging system capable of updating arrival time profiles at
frame rates of approximately 2 frames per second (fps) with 1-D arrays and up to
0.81 fps for 1.75-D arrays, depending on the desired near-field phase correction
algorithm. A novel feature included in this system is the ability to update the
aberration profile at multiple beam locations for 1-D arrays. The features of
this real-time adaptive imaging system are illustrated in tissue-mimicking
phantoms with physical near-field phase screens and evaluated in clinical breast
tissue with a 1.75-D array. The contrast-to-noise ratio (CNR) of anechoic cysts
was shown to improve dramatically in the tissue-mimicking phantoms. In breast
tissue, the width of point-like targets showed significant improvement: a
reduction of 26.2% on average. Brightness of these targets, however, marginally
decreased by 3.9%. For larger structures such as cysts, little improvement in
features and CNR were observed, which is likely a result of the system assuming
an infinite isoplanatic patch size for the 1.75-D arrays. The necessary
requirements for constructing a real-time adaptive imaging system are also
discussed.
PMID- 17036792
TI - Intravascular ultrasound tissue harmonic imaging in vivo.
AB - Tissue harmonic imaging (THI) has been shown to increase image quality of medical
ultrasound in the frequency range from 2 to 10 MHz and might, therefore, also be
used to improve image quality in intravascular ultrasound (IVUS). In this study
we constructed a prototype IVUS system that could operate in both fundamental
frequency and second harmonic imaging modes. This system uses a conventional,
continuously rotating, single-element IVUS catheter and was operated in
fundamental 20 MHz, fundamental 40 MHz, and harmonic 40 MHz modes (transmit 20
MHz, receive 40 MHz). Hydrophone beam characterization measurements demonstrated
the build-up of a second harmonic signal as a function of increasing pressure.
Imaging experiments were conducted in both a tissue-mimicking phantom and in an
atherosclerotic animal model in vivo. Acquisitions of fundamental 20 and 40 MHz
and second harmonic acquisitions resulted in cross sections of the phantom and a
rabbit aorta. The harmonic results of the imaging experiments showed the
feasibility of intravascular THI with a conventional IVUS catheter both in a
phantom and in vivo. The harmonic acquisitions also showed the potential of THI
to reduce image artifacts compared to fundamental imaging.
PMID- 17036793
TI - Multigate transcranial Doppler ultrasound system with real-time embolic signal
identification and archival.
AB - An integrated system for acquisition and processing of intracranial and
extracranial Doppler signals and automatic embolic signal detection has been
developed. The hardware basis of the system is a purpose-built
acquisition/processing board that includes a multigate Doppler unit controlled
through a computer. The signal-processing engine of the system contains a fast
Fourier transform (FFT)-based, spectral-analysis unit and an embolic signal
detection unit using expert system reasoning theory. The system is designed so
that up to four receive gates from a single transducer can be used to provide
useful reasoning information to the embolic signal-detection unit. Alternatively,
two transducers can be used simultaneously, either for bilateral transcranial
Doppler (TCD) investigations or for simultaneous intra- and extracranial
investigation of different arteries. The structure of the software will allow the
future implementation of embolus detection algorithms that use the information
from all four channels when a single transducer is used, or of independent
embolus detection in two sets of two channels when two transducers are used. The
user-friendly system has been tested in-vitro, and it has demonstrated a 93.6%
sensitivity for micro-embolic signal (MES) identification. Preliminary in-vivo
results also are encouraging.
PMID- 17036795
TI - Trajectory tracking of piezoelectric positioning stages using a dynamic sliding
mode control.
AB - Trajectory tracking performance of a piezoelectric positioning stage almost
depends on whether the tracking controller can effectively compensate the
inherent hysteresis phenomenon. In this paper, a dynamic sliding-mode control
(DSMC) with backstepping is proposed for the trajectory tracking of the
piezoelectric positioning stage, which is suitable for a component of scanning
microscopes. An equivalent model developed from a linear motion dynamics with
addition of the hysteresis nonlinearity and strain-dependent function first is
proposed to approximately represent the dynamics of motion of a one-dimensional
piezoelectric positioning stage. Then, based on the equivalent model, the DSMC
with an asymptotical sliding surface is proposed for the trajectory tracking
control of the piezoelectric positioning stage. Moreover, the analysis of
stability can be completed by mathematics, and the convergence rate of the
tracking error can be governed by the choice of the control parameter values.
Using the DSMC to trajectory tracking control, the piezoelectric positioning
stage becomes more suitable for practical applications, especially with the need
of various trajectories tracking in microscopy. To validate the proposed control
scheme, a computer-based controller and a piezoelectric positioning stage with a
capacitive displacement sensor are implemented. Experimental results illustrate
the feasibility of the proposed controller for trajectory tracking applications.
PMID- 17036794
TI - High reliability outdoor sonar prototype based on efficient signal coding.
AB - Many mobile robots and autonomous vehicles designed for outdoor operation have
incorporated ultrasonic sensors in their navigation systems, whose function is
mainly to avoid possible collisions with very close obstacles. The use of these
systems in more precise tasks requires signal encoding and the incorporation of
pulse compression techniques that have already been used with success in the
design of high-performance indoor sonars. However, the transmission of ultrasonic
encoded signals outdoors entails a new challenge because of the effects of
atmospheric turbulence. This phenomenon causes random fluctuations in the phase
and amplitude of traveling acoustic waves, a fact that can make the encoded
signal completely unrecognizable by its matched receiver. Atmospheric turbulence
is investigated in this work, with the aim of determining the conditions under
which it is possible to assure the reliable outdoor operation of an ultrasonic
pulse compression system. As a result of this analysis, a novel sonar prototype
based on complementary sequences coding is developed and experimentally tested.
This encoding scheme provides the system with very useful additional features,
namely, high robustness to noise, multi-mode operation capability (simultaneous
emissions with minimum cross talk interference), and the possibility of applying
an efficient detection algorithm that notably decreases the hardware resource
requirements.
PMID- 17036796
TI - Complex permittivity measurements of ferroelectrics employing composite
dielectric resonator technique.
AB - Composite cylindrical TE(0n1) mode dielectric resonator has been used for the
complex permittivity measurements of ferroelectrics at frequency about 8.8 GHz.
Rigorous equations have been derived that allowed us to find a relationship
between measured resonance frequency and Q-factor and the complex permittivity.
It has been shown that the choice of appropriate diameter of a sample together
with rigorous complex angular frequency analysis allows precise measurements of
various ferroelectric. Proposed technique can be used for materials having both
real and imaginary part of permittivity as large as a few thousand. Variable
temperature measurements were performed on a PbMg(1/3)Nb(2/3)O3 (PMN) ceramic
sample, and the measured complex permittivity have shown good agreement with the
results of measurements obtained on the same sample at lower frequencies (0.1-1.8
GHz).
PMID- 17036797
TI - Merits of PM noise measurement over noise figure: a study at microwave
frequencies.
AB - This paper primarily addresses the usefulness of phase-modulation (PM) noise
measurements versus noise figure (NF) measurements in characterizing the merit of
an amplifier. The residual broadband (white PM) noise is used as the basis for
estimating the NF of an amplifier. We have observed experimentally that many
amplifiers show an increase in the broadband noise of 1 to 5 dB as the signal
level through the amplifier increases. This effect is linked to input power
through the amplifier's nonlinear intermodulation distortion. Consequently, this
effect is reduced as linearity is increased. We further conclude that, although
NF is sometimes used as a selection criteria for an amplifier for low-level
signal, NF yields no information about potentially important close-to-carrier 1/f
noise of an amplifier nor broadband noise in the presence of a high-level signal,
but a PM noise measurements does. We also have verified experimentally that the
single-sideband PM noise floor of an amplifier due to thermal noise is -177
dBc/Hz, relative to a carrier input power of 0 dBm.
PMID- 17036798
TI - Finite difference time domain methods for piezoelectric crystals.
AB - The numerical simulation of acoustic wave propagation through piezoelectric
crystals using the finite-difference time-domain (FDTD) method is introduced. The
update equations for the velocity and stress fields are derived and applied to
the propagation of ultrasonic waves in three substrates. The concept of the
perfectly matched layer (PML), first introduced for the simulation of
electromagnetic waves, is extended to the simulation of mechanical waves. The
technique is shown to be effective for some crystals, but the PML is found to
exhibit numerical instabilities for others.
PMID- 17036799
TI - Blind multiridge detection for automatic nondestructive testing using ultrasonic
signals.
AB - Ultrasonic imaging has been a significant means for nondestructive testing (NDT).
Recently the NDT techniques via the ultrasonic instrumentation have shown the
striking capability of the quality control for the material fabrication industry.
To the best of our knowledge, all existing signal processing methods require
either the a priori information of the ultrasonic signature signals or the manual
segmentation operation to achieve the reliable parameters that characterize the
corresponding mechanical properties. In this paper, we first provide a general
mathematical model for the ultrasonic signals collected by the pulse-echo
sensors, then design a totally blind novel signal processing NDT technique
relying on neither a priori signal information nor any manual effort. Based on
the automatic selection of optimal frame sizes using a proposed new criterion in
our scheme, the signature signal can be blindly extracted for further robust
multiridge detection. The detected ridge information can be used to estimate the
transmission and attenuation coefficients associated with any arbitrary material
sample for the fabrication quality control.
PMID- 17036800
TI - Suppression of reflection coefficients of surface acoustic wave filters using
quadrature hybrids.
AB - This paper proposes a simple technique to suppress the reflection coefficients
S11 and S22 of surface acoustic wave (SAW) filters. Two identical SAW filters are
sandwiched in between two quadrature hybrids, where their two ports are used as
input and output, and others are terminated by matched loads. First, it is shown
by simulation that both [S11] and [S22] are suppressed to be less than -20 dB
without deteriorating the transmission characteristics. Next, two hybrids using
microstrip lines were fabricated, and two RF SAW filters for GSM850 were
sandwiched in between them. The result showed that the maximum [S11] within the
passband was improved from -12.5 dB to -21.7 dB, i.e., 9.2 dB suppression of
[S11] was achieved by sacrificing only the insertion loss of less than 0.6 dB. We
also attempted to replace the microstrip lines with lumped elements. In this
case, the maximum [S11] within the passband was improved more than 7.5 dB with
the increased insertion loss of less than 1.5 dB. Finally, simple discussion is
given on the inclusion of the transformer function in the quadrature hybrid.
PMID- 17036801
TI - Comparison of conventional and collapsed region operation of capacitive
micromachined ultrasonic transducers.
AB - We report experimental results from a comparative study on collapsed region and
conventional region operation of capacitive micromachined ultrasonic transducers
(CMUTs) fabricated with a wafer bonding technique. Using ultrasonic pulse-echo
and pitch-catch measurements, we characterized single elements of 1-D CMUT arrays
operating in oil. The experimental results from this study agreed with the
simulation results: a CMUT operating in the collapsed region produced a higher
maximum output pressure than a CMUT operated in the conventional region at 90% of
its collapse voltage (3 kPa/V vs. 16.1 kPa/V at 2.3 MHz). While the pulse-echo
fractional bandwidth (126%) was higher in the collapsed region operation than in
the conventional operation (117%), the pulse-echo amplitude in collapsed region
operation was 11 dB higher than in conventional region operation. Furthermore,
within the range of tested bias voltages, the output pressure monotonously
increased with increased bias during collapsed region operation. It was also
found that in the conventional mode, short AC pulses (larger than the collapse
voltage) could be applied without collapsing the membranes. Finally, while no
significant difference was observed in reflectivity of the CMUT face between the
two regions of operation, hysteretic behavior of the devices was identified in
the collapsed region operation.
PMID- 17036802
TI - Study of the bending modes in circular quartz resonators.
AB - An experimental and theoretical study of bending modes in a partially electroded
circular piezoelectric quartz (AT-cut) with free edge is presented. The quartz is
excited by a voltage pulse applied on the electrodes, and its surface is scanned
by a laser vibrometer that measures the out-of-plane displacements. The classical
theory of bending of thin disks is used to describe the flexural modes at
frequencies lower than the first thickness shear resonance (6 MHz). A fairly good
agreement is found between experimental and theoretical results for the forced
mode shapes and for the resonance frequencies. However, it appears that the two
springs used to maintain the disk in position introduce extra clamping
conditions. Several source shapes were studied, among which a collection of an
arbitrary number of forces is particularly useful. The two-dimensional wavenumber
representation shows the presence of anisotropy related to the crystallographic
axes at higher frequencies, which is not predicted by the model. The experimental
phase velocities are compared to those given by the classical theory of disks and
to those of Lamb A(0) mode. This study confirms the correspondence at low
frequencies between the A(0) mode and the bending eigenmodes of a disk with
finite size.
PMID- 17036803
TI - Beam steering with segmented annular arrays.
AB - Two-dimensional (2-D) arrays of squared matrix have maximum periodicity in their
main directions; consequently, they require half wavelength (lambda/2),
interelement spacing to avoid grating lobes. This condition gives rise to well
known problems derived from the huge number of array elements and from their
small size. In contrast, 2-D arrays with curvilinear configuration produce lower
grating lobes and, therefore, allow the element size to be increased beyond
lambda/2. Using larger elements, these arrays have the advantage of reducing the
number of elements and of increasing the signal-to-noise ratio (SNR). In this
paper, the beamforming properties of segmented annular phased arrays are
theoretically analyzed and compared with the equivalent squared matrix array. In
the first part, point-like elements are considered in order to facilitate the
field analysis with respect to the array structure. Afterward, the effect of the
element size on the steered beam properties also is presented. In the examples,
it is shown that the segmented annular array has notably lower grating lobes than
the equivalent squared matrix array and that it is possible to design segmented
annular arrays with interelement distance higher than lambda whose beam
characteristics are perfectly valid for volumetric imaging applications.
PMID- 17036804
TI - Photoacoustic flow measurements with gold nanoparticles.
AB - The hypothesis that quantitative blood flow measurements are feasible with the
time-intensity based method in photoacoustic imaging using gold nanoparticles as
contrast agent is experimentally tested. The in vitro results show good linearity
between the measurements and the theory, thus suggesting the potential of
relative photoacoustic flow measurements with gold nanoparticles.
PMID- 17036805
TI - Effects of piezoelectric coupling on Bechmann's number for thickness-twist waves
in a plate of hexagonal crystals.
AB - Solutions for thickness-twist waves in a piezoelectric plate of 6-mm crystals
with surface mass layers are obtained. The solutions are used to determine
Bechmann's number for designing electrode size of devices operating with these
waves. This generalizes the existing knowledge on Bechmann's number by the
inclusion of piezoelectric coupling. It is shown that this coupling plays a role
as important as or more important than the electrode inertia. The results are of
fundamental importance to resonator design, in particular thin film resonators of
ZnO and AlN.
PMID- 17036806
TI - Evaluating sensor reliability in classification problems based on evidence
theory.
AB - This paper presents a new framework for sensor reliability evaluation in
classification problems based on evidence theory (or the Dempster-Shafer theory
of belief functions). The evaluation is treated as a two-stage training process.
First, the authors assess the static reliability from a training set by comparing
the sensor classification readings with the actual values of data, which are both
represented by belief functions. Information content contained in the actual
values of each target is extracted to determine its influence on the evaluation.
Next, considering the ability of the sensor to understand a dynamic working
environment, the dynamic reliability is evaluated by measuring the degree of
consensus among a group of sensors. Finally, the authors discuss why and how to
combine these two kinds of reliabilities. A significant improvement using the
authors' method is observed in numerical simulations as compared with the
recently proposed method.
PMID- 17036807
TI - A probabilistic model for binaural sound localization.
AB - This paper proposes a biologically inspired and technically implemented sound
localization system to robustly estimate the position of a sound source in the
frontal azimuthal half-plane. For localization, binaural cues are extracted using
cochleagrams generated by a cochlear model that serve as input to the system. The
basic idea of the model is to separately measure interaural time differences and
interaural level differences for a number of frequencies and process these
measurements as a whole. This leads to two-dimensional frequency versus time
delay representations of binaural cues, so-called activity maps. A probabilistic
evaluation is presented to estimate the position of a sound source over time
based on these activity maps. Learned reference maps for different azimuthal
positions are integrated into the computation to gain time-dependent discrete
conditional probabilities. At every timestep these probabilities are combined
over frequencies and binaural cues to estimate the sound source position. In
addition, they are propagated over time to improve position estimation. This
leads to a system that is able to localize audible signals, for example human
speech signals, even in reverberating environments.
PMID- 17036808
TI - Design and stabilization of sampled-data neural-network-based control systems.
AB - This paper presents the design and stability analysis of a sampled-data neural
network-based control system. A continuous-time nonlinear plant and a sampled
data three-layer fully connected feedforward neural-network-based controller are
connected in a closed loop to perform the control task. Stability conditions will
be derived to guarantee the closed-loop system stability. Linear-matrix
inequality- and genetic-algorithm-based approaches will be employed to obtain the
largest sampling period and the connection weights of the neural network subject
to the considerations of the system stability and performance. An application
example will be given to illustrate the design procedure and effectiveness of the
proposed approach.
PMID- 17036809
TI - Evolving compact and interpretable Takagi-Sugeno fuzzy models with a new encoding
scheme.
AB - Developing Takagi-Sugeno fuzzy models by evolutionary algorithms mainly requires
three factors: an encoding scheme, an evaluation method, and appropriate
evolutionary operations. At the same time, these three factors should be designed
so that they can consider three important aspects of fuzzy modeling: modeling
accuracy, compactness, and interpretability. This paper proposes a new
evolutionary algorithm that fulfills such requirements and solves fuzzy modeling
problems. Two major ideas proposed in this paper lie in a new encoding scheme and
a new fitness function, respectively. The proposed encoding scheme consists of
three chromosomes, one of which uses unique chained possibilistic representation
of rule structure. The proposed encoding scheme can achieve simultaneous
optimization of parameters of antecedent membership functions and rule structures
with the new fitness function developed in this paper. The proposed fitness
function consists of five functions that consider three evaluation criteria in
fuzzy modeling problems. The proposed fitness function guides evolutionary search
direction so that the proposed algorithm can find more accurate compact fuzzy
models with interpretable antecedent membership functions. Several evolutionary
operators that are appropriate for the proposed encoding scheme are carefully
designed. Simulation results on three modeling problems show that the proposed
encoding scheme and the proposed fitness functions are effective in finding
accurate, compact, and interpretable Takagi-Sugeno fuzzy models. From the
simulation results, it is shown that the proposed algorithm can successfully find
fuzzy models that approximate the given unknown function accurately with a
compact number of fuzzy rules and membership functions. At the same time, the
fuzzy models use interpretable antecedent membership functions, which are helpful
in understanding the underlying behavior of the obtained fuzzy models.
PMID- 17036810
TI - Generalized disjunction decomposition for evolvable hardware.
AB - Evolvable hardware (EHW) refers to self-reconfiguration hardware design, where
the configuration is under the control of an evolutionary algorithm (EA). One of
the main difficulties in using EHW to solve real-world problems is scalability,
which limits the size of the circuit that may be evolved. This paper outlines a
new type of decomposition strategy for EHW, the "generalized disjunction
decomposition" (GDD), which allows the evolution of large circuits. The proposed
method has been extensively tested, not only with multipliers and parity bit
problems traditionally used in the EHW community, but also with logic circuits
taken from the Microelectronics Center of North Carolina (MCNC) benchmark library
and randomly generated circuits. In order to achieve statistically relevant
results, each analyzed logic circuit has been evolved 100 times, and the average
of these results is presented and compared with other EHW techniques. This
approach is necessary because of the probabilistic nature of EA; the same logic
circuit may not be solved in the same way if tested several times. The proposed
method has been examined in an extrinsic EHW system using the (1 + lambda)
evolution strategy. The results obtained demonstrate that GDD significantly
improves the evolution of logic circuits in terms of the number of generations,
reduces computational time as it is able to reduce the required time for a single
iteration of the EA, and enables the evolution of larger circuits never before
evolved. In addition to the proposed method, a short overview of EHW systems
together with the most recent applications in electrical circuit design is
provided.
PMID- 17036811
TI - Design and control of an IPMC wormlike robot.
AB - This paper presents an innovative wormlike robot controlled by cellular neural
networks (CNNs) and made of an ionic polymer-metal composite (IPMC) self-actuated
skeleton. The IPMC actuators, from which it is made of, are new materials that
behave similarly to biological muscles. The idea that inspired the work is the
possibility of using IPMCs to design autonomous moving structures. CNNs have
already demonstrated their powerfulness as new structures for bio-inspired
locomotion generation and control. The control scheme for the proposed IPMC
moving structure is based on CNNs. The wormlike robot is totally made of IPMCs,
and each actuator has to carry its own weight. All the actuators are connected
together without using any other additional part, thereby constituting the robot
structure itself. Worm locomotion is performed by bending the actuators
sequentially from "tail" to "head," imitating the traveling wave observed in real
world undulatory locomotion. The activation signals are generated by a CNN. In
the authors' opinion, the proposed strategy represents a promising solution in
the field of autonomous and light structures that are capable of reconfiguring
and moving in line with spatial-temporal dynamics generated by CNNs.
PMID- 17036812
TI - Control architecture for human-robot integration: application to a robotic
wheelchair.
AB - Completely autonomous performance of a mobile robot within noncontrolled and
dynamic environments is not possible yet due to different reasons including
environment uncertainty, sensor/software robustness, limited robotic abilities,
etc. But in assistant applications in which a human is always present, she/he can
make up for the lack of robot autonomy by helping it when needed. In this paper,
the authors propose human-robot integration as a mechanism to augment/improve the
robot autonomy in daily scenarios. Through the human-robot-integration concept,
the authors take a further step in the typical human-robot relation, since they
consider her/him as a constituent part of the human-robot system, which takes
full advantage of the sum of their abilities. In order to materialize this human
integration into the system, they present a control architecture, called
architecture for human-robot integration, which enables her/him from a high
decisional level, i.e., deliberating a plan, to a physical low level, i.e.,
opening a door. The presented control architecture has been implemented to test
the human-robot integration on a real robotic application. In particular, several
real experiences have been conducted on a robotic wheelchair aimed to provide
mobility to elderly people.
PMID- 17036813
TI - Chemical plume source localization.
AB - This paper addresses the problem of estimating a likelihood map for the location
of the source of a chemical plume using an autonomous vehicle as a sensor probe
in a fluid flow. The fluid flow is assumed to have a high Reynolds number.
Therefore, the dispersion of the chemical is dominated by turbulence, resulting
in an intermittent chemical signal. The vehicle is capable of detecting above
threshold chemical concentration and sensing the fluid flow velocity at the
vehicle location. This paper reviews instances of biological plume tracing and
reviews previous strategies for a vehicle-based plume tracing. The main
contribution is a new source-likelihood mapping approach based on Bayesian
inference methods. Using this Bayesian methodology, the source-likelihood map is
propagated through time and updated in response to both detection and
nondetection events. Examples are included that use data from in-water testing to
compare the mapping approach derived herein with the map derived using a
previously existing technique.
PMID- 17036814
TI - Recursive camera-motion estimation with the trifocal tensor.
AB - In this paper, an innovative extended Kalman filter (EKF) algorithm for pose
tracking using the trifocal tensor is proposed. In the EKF, a constant-velocity
motion model is used as the dynamic system, and the trifocal-tensor constraint is
incorporated into the measurement model. The proposed method has the advantages
of those structure- and-motion-based approaches in that the pose sequence can be
computed with no prior information on the scene structure. It also has the
strengths of those model-based algorithms in which no updating of the three
dimensional (3-D) structure is necessary in the computation. This results in a
stable, accurate, and efficient algorithm. Experimental results show that the
proposed approach outperformed other existing EKFs that tackle the same problem.
An extension to the pose-tracking algorithm has been made to demonstrate the
application of the trifocal constraint to fast recursive 3-D structure recovery.
PMID- 17036815
TI - Dynamic calibration of pan-tilt-zoom cameras for traffic monitoring.
AB - Pan-tilt-zoom (PTZ) cameras have been widely used in recent years for monitoring
and surveillance applications. These cameras provide flexible view selection as
well as a wider observation range. This makes them suitable for vision-based
traffic monitoring and enforcement systems. To employ PTZ cameras for image
measurement applications, one first needs to calibrate the camera to obtain
meaningful results. For instance, the accuracy of estimating vehicle speed
depends on the accuracy of camera calibration and that of vehicle tracking
results. This paper presents a novel calibration method for a PTZ camera
overlooking a traffic scene. The proposed approach requires no manual operation
to select the positions of special features. It automatically uses a set of
parallel lane markings and the lane width to compute the camera parameters,
namely, focal length, tilt angle, and pan angle. Image processing procedures have
been developed for automatically finding parallel lane markings. Interesting
experimental results are presented to validate the robustness and accuracy of the
proposed method.
PMID- 17036816
TI - New pose-detection method for self-calibrated cameras based on parallel lines and
its application in visual control system.
AB - In this paper, a new method is proposed to detect the pose of an object with two
cameras. First, the intrinsic parameters of the cameras are self-calibrated with
two pairs of parallel lines that are orthogonal. Then, the poses of the cameras
relative to the parallel lines are deduced, and the rotational transformation
between the two cameras is calculated. With the intrinsic parameters and the
relative pose of the two cameras, a method is proposed to obtain the poses of a
line, plane, and rigid object. Furthermore, a new visual-control method is
developed using a pose detection rather than a three-dimensional reconstruction.
Experiments are conducted to verify the effectiveness of the proposed method.
PMID- 17036817
TI - Combining genetic algorithms and Lyapunov-based adaptation for online design of
fuzzy controllers.
AB - This paper proposes a hybrid approach for the design of adaptive fuzzy
controllers (FCs) in which two learning algorithms with different characteristics
are merged together to obtain an improved method. The approach combines a genetic
algorithm (GA), devised to optimize all the configuration parameters of the FC,
including the number of membership functions and rules, and a Lyapunov-based
adaptation law performing a local tuning of the output singletons of the
controller, and guaranteeing the stability of each new controller investigated by
the GA. The effectiveness of the proposed method is confirmed using both
numerical simulations on a known case study and experiments on a nonlinear
hardware benchmark.
PMID- 17036818
TI - A vertical-energy-thresholding procedure for data reduction with multiple complex
curves.
AB - Due to the development of sensing and computer technology, measurements of many
process variables are available in current manufacturing processes. It is very
challenging, however, to process a large amount of information in a limited time
in order to make decisions about the health of the processes and products. This
paper develops a "preprocessing" procedure for multiple sets of complicated
functional data in order to reduce the data size for supporting timely decision
analyses. The data type studied has been used for fault detection, root-cause
analysis, and quality improvement in such engineering applications as automobile
and semiconductor manufacturing and nanomachining processes. The proposed
vertical-energy-thresholding (VET) procedure balances the reconstruction error
against data-reduction efficiency so that it is effective in capturing key
patterns in the multiple data signals. The selected wavelet coefficients are
treated as the "reduced-size" data in subsequent analyses for decision making.
This enhances the ability of the existing statistical and machine-learning
procedures to handle high-dimensional functional data. A few real-life examples
demonstrate the effectiveness of our proposed procedure compared to several ad
hoc techniques extended from single-curve-based data modeling and denoising
procedures.
PMID- 17036819
TI - Multiscale classification using nearest neighbor density estimates.
AB - Density estimates based on k-nearest neighbors have useful applications in
nonparametric discriminant analysis. In classification problems, optimal values
of k are usually estimated by minimizing the cross-validated misclassification
rates. However, these cross-validation techniques allow only one value of k for
each population density estimate, while in a classification problem, the optimum
value of k for a class may also depend on its competing population densities.
Further, it is computationally difficult to minimize the cross-validated error
rate when there are several competing populations. Moreover, in addition to
depending on the entire training data set, a good choice of k should also depend
on the specific observation to be classified. Therefore, instead of using a
single value of k for each population density estimate, it is more useful in
practice to consider the results for multiple values of k to arrive at the final
decision. This paper presents one such approach along with a graphical device,
which gives more information about classification results for various choices of
k and the related statistical uncertainties present there. The utility of this
proposed methodology has been illustrated using some benchmark data sets.
PMID- 17036820
TI - Bayesian model averaging of naive Bayes for clustering.
AB - This paper considers a Bayesian model-averaging (MA) approach to learn an
unsupervised naive Bayes classification model. By using the expectation model
averaging (EMA) algorithm, which is proposed in this paper, a unique naive Bayes
model that approximates an MA over selective naive Bayes structures is obtained.
This algorithm allows to obtain the parameters for the approximate MA clustering
model in the same time complexity needed to learn the maximum-likelihood model
with the expectation-maximization algorithm. On the other hand, the proposed
method can also be regarded as an approach to an unsupervised feature subset
selection due to the fact that the model obtained by the EMA algorithm
incorporates information on how dependent every predictive variable is on the
cluster variable.
PMID- 17036821
TI - Robustly stable adaptive control of a tandem of master-slave robotic manipulators
with force reflection by using a multiestimation scheme.
AB - The problem of controlling a tandem of robotic manipulators composing a
teleoperation system with force reflection is addressed in this paper. The final
objective of this paper is twofold: 1) to design a robust control law capable of
ensuring closed-loop stability for robots with uncertainties and 2) to use the so
obtained control law to improve the tracking of each robot to its corresponding
reference model in comparison with previously existing controllers when the slave
is interacting with the obstacle. In this way, a multiestimation-based adaptive
controller is proposed. Thus, the master robot is able to follow more accurately
the constrained motion defined by the slave when interacting with an obstacle
than when a single-estimation-based controller is used, improving the
transparency property of the teleoperation scheme. The closed-loop stability is
guaranteed if a minimum residence time, which might be updated online when
unknown, between different controller parameterizations is respected.
Furthermore, the analysis of the teleoperation and stability capabilities of the
overall scheme is carried out. Finally, some simulation examples showing the
working of the multiestimation scheme complete this paper.
PMID- 17036822
TI - FCMAC-BYY: fuzzy CMAC using Bayesian Ying-Yang learning.
AB - As an associative memory neural network model, the cerebellar model articulation
controller (CMAC) has attractive properties of fast learning and simple
computation, but its rigid structure makes it difficult to approximate certain
functions. This research attempts to construct a novel neural fuzzy CMAC, in
which Bayesian Ying-Yang (BYY) learning is introduced to determine the optimal
fuzzy sets, and a truth-value restriction inference scheme is subsequently
employed to derive the truth values of the rule weights of implication rules. The
BYY is motivated from the famous Chinese ancient Ying-Yang philosophy: everything
in the universe can be viewed as a product of a constant conflict between
opposites-Ying and Yang, a perfect status is reached when Ying and Yang achieve
harmony. The proposed fuzzy CMAC (FCMAC)-BYY enjoys the following advantages.
First, it has a higher generalization ability because the fuzzy rule sets are
systematically optimized by BYY; second, it reduces the memory requirement of the
network by a significant degree as compared to the original CMAC; and third, it
provides an intuitive fuzzy logic reasoning and has clear semantic meanings. The
experimental results on some benchmark datasets show that the proposed FCMAC-BYY
outperforms the existing representative techniques in the research literature.
PMID- 17036823
TI - Globally asymptotic stability of a class of neutral-type neural networks with
delays.
AB - Several stability conditions for a class of systems with retarded-type delays are
presented in the literature. However, no results have yet been presented for
neural networks with neutral-type delays. Accordingly, this correspondence
investigates the globally asymptotic stability of a class of neutral-type neural
networks with delays. This class of systems includes Hopfield neural networks,
cellular neural networks, and Cohen-Grossberg neural networks. Based on the
Lyapunov stability method, two delay-independent sufficient stability conditions
are derived. These stability conditions are easily checked and can be derived
from the connection matrix and the network parameters without the requirement for
any assumptions regarding the symmetry of the interconnections. Two illustrative
examples are presented to demonstrate the validity of the proposed stability
criteria.
PMID- 17036824
TI - Stochastic automata-based estimators for adaptively compressing files with
nonstationary distributions.
AB - This correspondence shows that learning automata techniques, which have been
useful in developing weak estimators, can be applied to data compression
applications in which the data distributions are nonstationary. The adaptive
coding scheme utilizes stochastic learning-based weak estimation techniques to
adaptively update the probabilities of the source symbols, and this is done
without resorting to either maximum likelihood, Bayesian, or sliding-window
methods. The authors have incorporated the estimator in the adaptive Fano coding
scheme and in an adaptive entropy-based scheme that "resembles" the well-known
arithmetic coding. The empirical results obtained for both of these adaptive
methods are obtained on real-life files that possess a fair degree of
nonstationarity. From these results, it can be seen that the proposed schemes
compress nearly 10% more than their respective adaptive methods that use maximum
likelihood estimator-based estimates.
PMID- 17036825
TI - Analysis of brute-force break-ins of a palmprint authentication system.
AB - Biometric authentication systems are widely applied because they offer inherent
advantages over classical knowledge-based and token-based personal-identification
approaches. This has led to the development of products using palmprints as
biometric traits and their use in several real applications. However, as
biometric systems are vulnerable to replay, database, and brute-force attacks,
such potential attacks must be analyzed before biometric systems are massively
deployed in security systems. This correspondence proposes a projected
multinomial distribution for studying the probability of successfully using brute
force attacks to break into a palmprint system. To validate the proposed model,
we have conducted a simulation. Its results demonstrate that the proposed model
can accurately estimate the probability. The proposed model indicates that it is
computationally infeasible to break into the palmprint system using brute-force
attacks.
PMID- 17036826
TI - Comments on "Dynamical optimal training for interval type-2 fuzzy neural network
(T2FNN)".
AB - In this comment, it will be shown that the backpropagation (BP) equations by Wang
et al. are not correct. These BP equations were used to tune the parameters of
the antecedent type-2 membership functions as well as the consequent part of the
interval type-2 fuzzy neural networks (T2FNNs). These incorrect equations would
have led to erroneous results, and hence this might affect the comparisons and
findings presented by Wang et al. This comment will highlight the correct BP
tuning equations for the T2FNN.
PMID- 17036828
TI - Twenty-five years of AIDS.
PMID- 17036827
TI - Comments on "A modified reachability tree approach to analysis of unbounded Petri
nets".
AB - The above paper introduced the construction of a modified reachability tree (MRT)
for (unbounded) Petri nets and its application to reachability, liveness, and
deadlock analysis. This note shows via a counterexample that some of the MRT
properties claimed in the above paper are incorrect.
PMID- 17036829
TI - Off the record.
AB - Clinical dental records fulfil a variety of functions. Whilst there is no
standard data set for dental records, it is essential that these are
contemporaneous--that is, they are 'recorded at the time' A good written record
should contain details of the patient's identification data, medical and dental
history, clinical examination, diagnosis, treatment plan, reference to consent,
and progress notes. This paper covers these aspects in detail, and provides
information on how long records should be stored, and who may access clinical
records. CLINICAL RELEVANCE: The recording of contemporaneous patient/treatment
information is central to treatment planning and good patient care.
PMID- 17036830
TI - Zirconia-based all-ceramic crowns and bridges: three case reports.
AB - The search for a clinically viable all-ceramic bridge framework has been
monotonous. Until recently, few materials appear to have the necessary physical
and aesthetic properties. However, the development of yttrium tetragonal zirconia
polycrystals, and its adoption for use in dentistry by CAD CAM technology, may
hold promise as a crown and bridge framework, this being considered suitable for
single and multiple units. However, to date, no long-term clinical studies have
been reported. This paper describes three cases in which zirconia frameworks were
used in crowns and bridges. CLINICAL RELEVANCE: For the patient wishing to
receive a non-metal crown or bridge, novel zirconia-based systems hold promise.
PMID- 17036831
TI - Common facial fractures: 2. management.
AB - This, the second of three articles, highlights the management of facial fractures
and the GDP's role in this. CLINICAL RELEVANCE: For patients who present to
dental practice with facial fractures, it is important that the dentist is able
to inform the patient of his/her likely management in hospital.
PMID- 17036832
TI - Vital tooth bleaching in dental practice: 3. Biological, dental and legal issues.
AB - The final section of this series examines both the evidence for the safety of
external bleaching with hydrogen peroxide and related products and the legal
position in the UK with regard to their sale and use in general dental practice.
Potential side-effects are examined, including biological effects and dental
effects, with a review of the current evidence. The EU Cosmetics and Medical
Device Directive are both described and their impact on the provision of tooth
bleaching in the UK is explained. The legal position in the UK renders the sale
and supply of solutions containing >0.1% peroxide illegal, and practitioners must
be aware of the underlying legislation and the basis upon which a prosecution may
be pursued. CLINICAL RELEVANCE: Clinicians considering using hydrogen peroxide
products must be aware of the safety issues surrounding their use and be able to
explain to patients the nature of the risk and also the likelihood of any given
patient experiencing them.
PMID- 17036833
TI - Allergic contact stomatitis from colophony.
AB - Colophony is an ubiquitous contact sensitizer which may be present in dental
materials, such as periodontal dressings, impression materials, cements, fix
adhesives and varnishes. Exposure to a sensitizer in a hypersensitive person may
initiate an allergic contact dermatitis/stomatitis. This usually occurs after
direct skin/mucosa contact with the sensitizer. This paper reports the case of a
colophony hypersensitive male who developed contact stomatitis after dental
treatment with a colophony-containing product. CLINICAL RELEVANCE: Sensitizing
colophony is present in Duraphat 2.26%F varnish, a fluoride varnish used all over
the world. A case of hypersensitivity to Duraphat 2.26%F varnish is presented in
a patient who, at the initial visit, indicated only an allergy to sticking
plasters.
PMID- 17036834
TI - Aspects of human disease.
AB - This series outlines, briefly, the clinical presentation, diagnosis and
management of the 31 chronic medical problems which are most common and important
in the developed countries, but space also precludes coverage of acute infections
and most malignant disease.
PMID- 17036835
TI - Physical signs for the general dental practitioner. Melkersson-Rosenthal
syndrome.
PMID- 17036836
TI - Watershed issues associated with Clostridium botulinum: a literature review.
AB - Botulism the disease, the related organism (Clostridium botulinum) and toxin have
gained renewed attention in these times of heightened homeland security and
bioterrorism preparedness. Since C. botulinum is ubiquitous in nature, botulism
outbreaks resulting from environmental exposure can be of concern to watershed
managers and drinking water utilities. This paper reviews aspects of naturally
occurring C. botulinum in light of concerns for source water watersheds.
Information regarding sources and occurrence of botulism, C. botulinum and
botulism toxins are discussed. Ecology and physiology of environmental C.
botulinum and cycles of disease are reviewed. Finally, the effectiveness of water
treatment and disinfection measures is discussed.
PMID- 17036837
TI - Abundance of pathogenic Escherichia coli, Salmonella typhimurium and Vibrio
cholerae in Nkonkobe drinking water sources.
AB - In order to study the prevalence of enteric pathogens capable of causing
infection and disease in the rural communities of Nkonkobe, bacterial isolates
were collected from several surface water and groundwater sources used by the
community for their daily water needs. By making use of selective culture media
and the 20E API kit, presumptive Escherichia coli, Salmonella spp. and Vibrio
cholerae isolates were obtained and then analysed by polymerase chain reaction
assays (PCR). The PCR successfully amplified from water samples a fragment of E.
coli uidA gene that codes for beta-D-glucuronidase which is a highly specific
characteristic of enteropathogenic E. coli, enterotoxigenic E. coli and entero
invasive E. coli. The PCR also amplified the epsM gene from water samples
containing toxigenic V. cholerae. Although E. coli was mostly detected in
groundwater sources, toxigenic V. cholerae was detected in both surface and
groundwater sources. There was a possibility of Salmonella typhimurium in Ngqele
and Dyamala borehole water samples. The presence of these pathogenic bacteria in
the above drinking water sources may pose a serious health risk to consumers.
PMID- 17036838
TI - Determination of protection zones for Dutch groundwater wells against virus
contamination--uncertainty and sensitivity analysis.
AB - Protection zones of shallow unconfined aquifers in The Netherlands were
calculated that allow protection against virus contamination to the level that
the infection risk of 10(-4) per person per year is not exceeded with a 95%
certainty. An uncertainty and a sensitivity analysis of the calculated protection
zones were included. It was concluded that protection zones of 1 to 2 years
travel time (206-418 m) are needed (6 to 12 times the currently applied travel
time of 60 days). This will lead to enlargement of protection zones, encompassing
110 unconfined groundwater well systems that produce 3 x 10(8) m3 y(-1) of
drinking water (38% of total Dutch production from groundwater). A smaller
protection zone is possible if it can be shown that an aquifer has properties
that lead to greater reduction of virus contamination, like more attachment.
Deeper aquifers beneath aquitards of at least 2 years of vertical travel time are
adequately protected because vertical flow in the aquitards is only 0.7 m per
year. The most sensitive parameters are virus attachment and inactivation. The
next most sensitive parameters are grain size of the sand, abstraction rate of
groundwater, virus concentrations in raw sewage and consumption of unboiled
drinking water. Research is recommended on additional protection by attachment
and under unsaturated conditions.
PMID- 17036840
TI - Low risk for helminth infection in wastewater-fed rice cultivation in Vietnam.
AB - This study was done to assess the risk of helminth infection in association with
wastewater-fed rice cultivation in an agricultural setting of Nam Dinh city,
Vietnam. In a cross sectional survey data were collected for 202 households in a
commune where wastewater was used for irrigation and for 201 households in a
commune that used river water. Parasitological examination was conducted on
single stool samples obtained from 1,088 individuals aged -15 years from the
households. The irrigation water used in both communes was enumerated for
helminth eggs and thermotolerant coliforms. The prevalence of infection with
Ascaris spp., Trichuris spp., and hookworm was 42.2%, 19.9% and 10.5%
respectively, with an overall prevalence of infection with any helminth of 53.4%.
Surprisingly, the prevalence of infection with Ascaris and Trichuris was lower
among people exposed to wastewater (containing 40-200 helminth eggs/l and 10(4)
thermotolerant coliforms/100 ml) compared to people exposed to river water that
contained lower worm egg and bacterial numbers. Poor sanitation and hygiene
practices and not using protective measures were important independent risk
factors for helminth infection. For hookworm infection, no significant difference
was observed between the wastewater exposed and unexposed groups. Children living
in the wastewater use area had a significantly better nutritional status than
those in the area using river water. This suggests a generally higher welfare
level of the wastewater use area. In conclusion, this study showed no evidence
that rice cultivation with wastewater poses a risk for helminth infection. More
detailed studies are needed on the reduction of fecal indicators and helminth
eggs in peri-urban wastewater-irrigated rice culture systems and on the relative
importance of wastewater irrigation compared to other risk factors for human
helminth infection such as poor sanitation and poverty.
PMID- 17036839
TI - Seasonal persistence and population characteristics of Escherichia coli and
enterococci in deep backshore sand of two freshwater beaches.
AB - We studied the shoreward and seasonal distribution of E. coil and enterococci in
sand (at the water table) at two southern Lake Michigan beaches-Dunbar and West
Beach (in Indiana). Deep, backshore sand (approximately 20 m inland) was
regularly sampled for 15 months during 2002-2003. E. coli counts were not
significantly different in samples taken at 5-m intervals from 0-40 m inland (P =
0.25). Neither E. coli nor enterococci mean counts showed any correlation or
differences between the two beaches studied. In laboratory experiments, E. coli
readily grew in sand supplemented with lake plankton, suggesting that in situ E.
coil growth may occur when temperature and natural organic sources are adequate.
Of the 114 sand enterococci isolates tested, positive species identification was
obtained for only 52 (46%), with E. faecium representing the most dominant
species (92%). Genetic characterization by ribotyping revealed no distinct
genotypic pattern (s) for E. coli, suggesting that the sand population was rather
a mixture of numerous strains (genotypes). These findings indicate that E. coli
and enterococci can occur and persist for extended periods in backshore sand at
the groundwater table. Although this study was limited to two beaches of southern
Lake Michigan, similar findings can be expected at other temperate freshwater
beaches. The long-term persistence of these bacteria, perhaps independent of
pollution events, complicates their use as indicator organisms. Further,
backshore sand at the water table may act as a reservoir for these bacteria and
potentially for human pathogens.
PMID- 17036841
TI - Monitoring source and domestic water quality in parallel with sanitary risk
identification in northern Mozambique to prioritise protection interventions.
AB - Microbiological water quality monitoring in Niassa province, Northern Mozambique,
shows groundwater is not, in general, grossly contaminated though contamination
levels are strongly linked to season and to risks observable at the wellhead,
especially risks dealing with wellhead hygiene and maintenance. Diarrhea
incidence, in general, is greatest in the rainy season suggesting poor wellhead
protection as a potential mechanism for well contamination. Comparison of source
water and stored water in the home shows that significant deterioration in source
water quality can occur once transport and storage in the home is undertaken but
that this deterioration is also related to the quality of the source water. This
study shows that a structured approach to water quality monitoring, with targeted
observations and an examination of the relationships between risk and water
quality, is important to identify the priority interventions to be undertaken.
PMID- 17036842
TI - Population similarity of enterococci and Escherichia coil in surface waters: A
predictive tool to trace the sources of fecal contamination.
AB - A biochemical fingerprinting method (the PhPlate system) was used to compare
similarities between Escherichia coli and enterococci populations from surface
water samples with those found in different animal species during the wet and the
dry seasons in order to predict the dominant source(s) of fecal contamination in
a local creek. A significant increase in the number and diversity of enterococci
was observed in the creek during the wet season. Enterococci population from
water samples also showed a higher population similarity with animal species than
did E. coli. A higher population similarity was found between both indicator
bacteria and animal species during the wet season with highest population
similarities found in dogs, horses, cows and kangaroos. In contrast, a low
population similarity was found for both fecal indicator bacteria from humans
with water samples during the wet and the dry seasons, indicating that humans are
not a major source of contamination in the studied creek. The results also
indicate that the population similarity analysis of enterococci population has an
advantage over E. coli in tracing the possible source(s) of contamination in the
studied creek and that population similarity analysis as used in this study can
be used to predict the source(s) of fecal contamination in surface waters.
PMID- 17036843
TI - Diffuse pollution in Oxford (Ohio, USA) watershed and performance of 'street
sweeping' as a 'best management practice' (BMP).
AB - Experimental results are described to evaluate the diffuse pollution profile
according to land use in the catchments and street sweeping as a best management
practice (BMP). We studied the variation of pollutant concentrations in outfalls
discharging runoff from residential, commercial and high-traffic areas and in
street sweeping. Pollution profiles varied with the land use in the catchments
and seasons along with other factors such as rainfall intensity, construction
works and street maintenance. Microbial indicator organisms were relatively high
in all three outfalls. Heavy metal concentrations were low with lead (Pb) as the
predominant heavy metal. The organic and solid contents were low but non
degradable and persistent. Relatively high quantities of pollutants were found in
street sweeps in all catchments suggesting street sweeping as an effective
measure to control diffuse pollution. Regular and frequent sweeping is important
as a BMP.
PMID- 17036844
TI - The health effects of flooding: Social research results from England and Wales.
AB - This paper presents interview survey data by social scientists using established
health measures on the health effects of flooding for residents in 30 locations
in England and Wales. Firstly, it examines the extent to which flooded residents
reported suffering physical and psychological health effects during and after the
event. Secondly, it explores the issue of whether these effects were long-lasting
by comparisons with the general population and with those at risk but not
flooded. In the study, about two thirds of the flood victims were found to have
scores on the General Health Questionnaire-12 scale indicative of mental health
problems (scores of 4+) at their worst time after flooding. The evidence of the
study also suggests that some flood victims suffered long term mental health
effects as a result of their experience of flooding. The study examines the
influence of a wide range of factors: characteristics of the flood event, types
of property, and socio-demographic and the intervening factors such as the extent
of family or community support that may explain the health effects of flooding.
It finds that a complex set of social and other factors are involved and that
some factors susceptible to human intervention such as having adequate flood
insurance cover are important factors in the stress experienced by flood victims.
PMID- 17036845
TI - Identification by microarray of a common pattern of gene expression in intact
intestine and cultured intestinal cells exposed to virulent Aeromonas hydrophila
isolates.
AB - The genus Aeromonas comprises known virulent and avirulent isolates and has been
implicated in waterborne disease. A common infection model of human
gastroenteritis associated with A. hydrophila uses neonatal mice. The goal of
this research was to evaluate whether a murine small intestinal cell line could
provide comparable results to the gene expression changes in the neonatal mouse
model. Changes in mRNA expression in host cell cultures and intestinal tissues
were measured after exposure to virulent Aeromonas hydrophila strains. A.
hydrophila caused the up-regulation of more than 200 genes in neonates and over
50 genes in cell culture. Twenty-six genes were found to be in common between the
two models, of which the majority are associated with the innate immune response.
PMID- 17036846
TI - Effects of temperature and sand on E. coil survival in a northern lake water
microcosm.
AB - A concern for public health officials is the presence of Escherichia coli (E.
coli), an indicator of fecal contamination, in monitoring recreational waters.
While E. coli is unlikely to cause disease in humans, its presence may indicate
other more pathogenic microorganisms. Many factors can lead to changes in the
survival of E. coli outside of the animal intestine and may affect the
probability of colonizing a new host. Survival of bacteria in recreational water
has been linked to water temperature, and most recently to the presence of sand
on the beach. This project looked at the survival of an environmental E. coli
isolate in lake water. Lake water microcosms were placed at 4, 10, 14, or 25
degrees C for up to 36 d and an enzyme-substrate test (Colisure, IDEXX Corp.) was
used to determine the most probable number (MPN) of E. coli/100 ml water. E. coli
numbers at all temperatures declined over the duration of the experiment. The
decline was most pronounced at 14 degrees C and was slowest at 4 degrees C. The
presence of sand in the microcosm increased the time that E. coli survived,
regardless of temperature. From a beach management standpoint, these findings
indicate that E.coli may persist in the environment in cooler water longer than
in the warmer water encountered in late summer.
PMID- 17036847
TI - Effect of soil depth and texture on fecal bacteria removal from septic effluents.
AB - This study evaluated the effectiveness of soils with different texture and depth
to treat fecal bacteria eluted from a house-hold septic effluent. The assessments
were accomplished by leaching undisturbed soil monoliths of 30, 45, and 60cm
thickness and 25cm in diameter, representing the four different textural groups
and hydraulic loadings recommended by the Kentucky Health Department, with
domestic wastewater effluent collected regularly from a house-hold septic system.
Eluent concentrations were monitored daily over a 15 day period for fecal
coliform and fecal streptococci concentrations. The results of the study indicate
an alarming frequency of failure to comply with United States Environmental
Protection Agency (USEPA) criteria for depth to groundwater, when using a 30 cm
vertical separation distance between the bottom of the drain-field and a limiting
soil interface. The treatment performance was especially poor in coarse-textured
soils. Although biomat development over time is expected to improve treatment,
the high influent levels of fecal bacteria pose great concerns for surface and
groundwater contamination. Fine-textured soils generally provided better
treatment efficiency and more consistent compliance with EPA standards. Treatment
efficiency and compliance usually improved with increasing soil depth, with the
60cm thickness providing the most consistent performance and compliance with
maximum discharge limit (MDL) requirements. The findings of this study document a
general inadequacy of the 30cm vertical separation distance to provide effective
treatment of septic effluents in Kentucky soils, particularly in coarse-textured
soils. Considering that increasing the soil depth thickness may be impractical in
many marginal soils, complementary or alternative treatment technologies should
be adopted to improve treatment efficiency and prevent further deterioration of
the quality of water resources.
PMID- 17036848
TI - A week we don't want to forget: lessons learned from Tulane.
AB - By the time I walked into the conference call at about 7 a.m. on Tuesday, August
30, HCA's Tulane hospital was surrounded by between four and six feet of water,
depending on the side of the building. The water was slowly rising. An estimated
1,300 people were trapped at Tulane Hospital. No CEO has ever had as much reason
to be proud of his company as I did during the next few days. We safely evacuated
Tulane's patients, staff members, and family members, coordinating more than 200
helicopter sorties to and from Tulane in the process. We transferred every
patient to a waiting hospital and took nearly every staff and family member to an
HCA-run shelter in Lafayette, Louisiana, where they were bathed, fed, inoculated,
given shelter, given access to prepaid cellular phones, and sent where they
needed to go. This, I believe, was one of HCA's greatest hours, but we also
learned many lessons from the catastrophic event. Although we hope and pray that
nothing like this ever happens again, the things we learned can be of use to the
healthcare community at large.
PMID- 17036849
TI - Hurricane Katrina and the healthcare infrastructure: A focus on disaster
preparedness, response, and resiliency.
AB - The aftermath of Hurricane Katrina provides a window of opportunity to address a
frail and failing healthcare system. Katrina was the rare incident that disrupted
the external systems supplying hospitals with key services and resources needed
for the organizations to function; increased the number of patients, both present
and expected, that required medical care; and affected directly the physical
plants of the hospitals, challenging their functionality. Sorting through and
gleaning useful lessons to increase the resilience of hospitals for this type of
catastrophic incident will take time and will require system-wide public health
planning and intervention. In this article, the authors focus on how hospitals
prepared for, responded to, and coped with Katrina. They also provide a brief
overview of the current situation and the healthcare crisis confronting hospitals
and communities in the region affected by Katrina and discuss the impending need
to develop disaster-resilient medical and healthcare systems. Planning, access to
adequate resources, networking, effective communication and coordination, and
training and education of doctors, nurses, technicians, and medical staff are
essential in the development of a resilient healthcare infrastructure that will
be able to provide the much needed services to populations affected by future
disasters.
PMID- 17036850
TI - Can it get any worse?
AB - THE TWO FEATURE articles presented in this issue of Frontiers of Health Services
Management speak to the challenges of Hurricane Katrina. The Tulane experience
lists a multitude of problems, solutions, and successes, whereas the article by
Drs. Rodriguez and Aguirre speaks to the impact on the infrastructure following
the hurricane. In the federal report, "The Federal Response to Hurricane
Katrina," the White House (2006) has labeled Katrina as "the most destructive
natural disaster in U.S. history." Dr. E. L. Quarantelli (2006) might call
Katrina a catastrophe. Regardless of what one calls the event, Hurricane Katrina
has shown that the challenges leading up to and following a disaster/catastrophe
will overwhelm everyone. People must understand that they cannot wait for a
government, any government, to help them. We must be prepared to help ourselves.
PMID- 17036851
TI - Keeping patients safe when disaster strikes.
PMID- 17036852
TI - Not for profit hospitals: balancing business and benefit.
PMID- 17036853
TI - [Subtle skin lesions in the midline as an indication of a neurodermal closing
defect].
AB - Three patients, aged 2, 2.5 and 24 years, presented with a skin lesion in the
median or paramedian area at the nose, in the lumbar region and between the
shoulders, respectively. The first patient suffered from recurrent infection, the
skin lesion of the second patient was a coincidental finding, and the third
patient had cosmetic problems. Although there were no signs of neurological
deficits, neurodermal closing defects were found by MRI. Two patients underwent
surgery to prevent infection and neurological complaints in the future. It is
stressed that even if there are no neurological signs or infections, congenital
dermal lesions situated in the midline should be considered as possible neural
tube defects and therefore analysed by MRI. Ifa neurodermal dysraphism is found,
patients should be referred to a neurosurgical centre. A good clinical assessment
of the neural lesion, clinical signs and age will determine whether surgical
resection is indicated to prevent or resolve neurological problems, infections or
cosmetic complaints.
PMID- 17036854
TI - [Treatment of patients with the chronic-fatigue syndrome].
AB - In the last few years, the chronic-fatigue syndrome has been recognised as an
important health problem. In a recent report, the Health Council of the
Netherlands suggested that the capacity for treatment be increased. Cognitive
behavioural therapy and graded exercise training are treatment options of first
choice. A recently published, uncontrolled evaluation of a Dutch clinical
rehabilitation programme based partly on these methods proved to be successful.
Unfortunately, due to the uncontrolled character of the study, it remains unclear
which elements in the treatment were responsible for the success. Which patients
should be included in a costly clinical rehabilitation programme also remains
unclear. More in general, there is room for empirical studies of treatment
allocation, not in the least because of the frequently occurring comorbidity.
Good progress has been made in the treatment of the chronic-fatigue syndrome, but
we are still far removed from evidence-based, stepped care, treatment programmes.
PMID- 17036855
TI - [Health effects of fish oil and fish oil supplements: consumption advice
sustained].
AB - Omega-3 fatty acids are thought to have beneficial effects on atherosclerosis.
Recently, the results ofa systematic review on the health effects of omega-3
fatty acids were published. The risk of cardiovascular death in subjects
randomised to taking omega-3 fats was not significantly decreased: relative risk
= 0.87 (95% CI: 0.73-1.03). In a 2004 Cochrane review, the same authors concluded
that there was a significant beneficial effect on total mortality, combined
cardiovascular endpoints and cancer. Inclusion of the recent 'Diet and
reinfarction trial' (DART-2-trial) had a decisive negative effect on the results
of the recent meta-analysis. Excluding this study resulted in a relative risk of
cardiovascular death of 0.83 (95% CI: 0.75-0.91). Since the DART-2 study had
methodological shortcomings, it still appears that recommending sufficient intake
of omega-3 fatty acids is justifiable, preferably by eating fish but ifnecessary
by using fish oil supplements, especially for patients at high risk of
cardiovascular disease.
PMID- 17036856
TI - [Hypospadias and congenital curvature of the penis in children and their surgical
treatment].
AB - Hypospadias is a congenital defect of the penis in which the urethral orifice is
located on the ventral aspect of the glans penis or, more proximally, on the
shaft or scrotum. Some type of hypospadias occurs in approximately 1 in 200 boys.
The defect can be minimal or so severe that the sex of the newborn is difficult
to determine. Many boys with hypospadias also have a congenital curvature of the
penis that needs correction. Corrective surgery is done preferably between the
ages of 6 and 12 months. The aim of surgery is to obtain a functionally and
cosmetically normal penis while limiting the psychological burden on the child as
much as possible. The common surgical procedures include: meatal advancement and
glanuloplasty (MAGPI), the tubularised incised plate (TIP) technique according to
Snodgrass, and vascularised foreskin flap-plasty. Urethral surgery for
hypospadias is accompanied by a relatively high number of complications and
should therefore be carried out by surgeons with sufficient experience.
PMID- 17036857
TI - [Clinical reasoning and decision-making in practice. A man with inexplicable
joint pain and subsequent poor clinical condition].
AB - A 52-year-old man presented with polyarthritis and was negative for rheumatoid
factor, anti-CCP and ANA. He was treated with low-dose methotrexate, the drug of
first choice in rheumatoid arthritis. The arthritis disappeared, but the patient
developed fever, progressive dyspnoea, appetite loss and weight loss. Upon
hospital admission his medication was stopped and community-acquired pneumonia
was diagnosed. The fever persisted despite antibiotic treatment. The tentative
diagnosis of rheumatoid arthritis was changed to systemic lupus erythematosus,
based on the change in clinical condition that could not be explained by
polyarthritis and seroconversion to ANA- and anti-dsDNA-positive. The patient was
treated with high-dose steroids and azathioprine and remained in remission for
more than 1 year after treatment. The ANA test remained strongly positive,
whereas anti-dsDNA was no longer detectable. This case stresses the limited value
of classification criteria for the diagnosis of rheumatoid arthritis. To
differentiate between rheumatoid arthritis and systemic lupus erythematosus,
tests for autoantibodies against citrullinated peptides can be used. To
differentiate between systemic lupus erythematosus and infection, tests for anti
dsDNA antibodies, antinuclear antibodies, C-reactive protein and complement can
be used.
PMID- 17036858
TI - [Diagnostic image (292). A man with a pulsatile temporal swelling].
AB - A 19-year-old man developed a pulsatile swelling in the left temporal area due to
a false aneurysm of the superficial temporal artery, two weeks after a blunt
trauma caused by a heading duel during a soccer match.
PMID- 17036859
TI - [Prevention of allergy is both useful and necessary].
AB - Refraining from smoking during pregnancy and giving exclusively breast feeding
for 4-6 months reduce the chance of allergic manifestations during the first 6
years of life and possibly longer. Hypoallergenic baby foods have a comparable
effect on food allergy and atopic eczema, but their long-term effects remain
uncertain. The prevention of allergy is therefore both possible and useful.
PMID- 17036860
TI - [Allergy prevention is an illusion].
AB - The recommendation that babies with a familial predisposition for allergic
diseases be given hypoallergenic baby food is based on studies that were
insufficiently blinded. The prevention of allergic sensitisation in the long term
has never been demonstrated. Exposure to allergens is not the determining factor
in the development of allergic diseases. It is probable that only the mild forms
of eczema are to a certain extent delayed. For the time being, therefore, the
prevention of allergy is an illusion.
PMID- 17036861
TI - [Favourable results of a rehabilitation programme with cognitive behavioural
therapy and graded physical activity in patients with the chronic-fatigue
syndrome].
AB - OBJECTIVE: To determine whether a specific course of interdisciplinary
rehabilitation might lead to clinically significant changes in fatigue,
experienced disability and physical function in patients with the chronic-fatigue
syndrome (CFS). DESIGN: Prospective and uncontrolled. METHOD: 'Het Roessingh', a
rehabilitation centre in Enschede, the Netherlands, has developed an
interdisciplinary clinical rehabilitation programme for patients with CFS in
cooperation with the 'Nijmeegs Kenniscentrum Chronische Vermoeidheid' [Chronic
Fatigue Knowledge Centre] in Nijmegen, the Netherlands. In this programme,
physical, mental and social activities are gradually increased on the basis of
cognitive behavioural principles and graded activity. Of the 127 successive
persons who enrolled for the therapy during the period from August 2000 to
December 2004, 99 fulfilled the inclusion criteria; they had a median duration of
symptoms of 6 years. The results of treatment were evaluated by a measurement
with the 'Checklist individuele spankracht' [Checklist individual muscle tone]
before and after treatment and the scores on the 'Patientspecifieke beperkingen'
[Patient-specific disability] and the Short form-36. The measured data were
complete in 74 patients. RESULTS: Before rehabilitation, the levels of fatigue,
disability and distress were high. After treatment, the studied population showed
significant improvement in fatigue, experienced disability and physical function.
The magnitude of the improvement was generally 'average'. At the end of
treatment, 70% of the patients were clinically less fatigued, 68% experienced
less disability and 55% functioned better physically. In 34% the level of fatigue
was normalised after treatment, but 9.5% of the patients was more fatigue.
CONCLUSION: The rehabilitation programme offered for CFS led to significant
improvements in function and fatigue.
PMID- 17036863
TI - [Kikuchi's histiocytic necrotising lymphadenitis: a benign disorder--not to be
confused with malignant lymphoma].
AB - A 26-year-old woman who later turned out to have the rarely seen histiocytic
necrotising lymphadenitis of Kikuchi was twice diagnosed incorrectly with
malignant T-cell lymphoma. She was treated with standard chemotherapy, whereas
Kikuchi's disease has a self-limiting course. Fear for recurrent lymphoma greatly
affected the patient's life until the proper diagnosis was ultimately made. This
occurred after the patient herself had seen in her dossier that the diagnosis
'Kikuchi's histiocytic lymphadenitis' had been proposed by two pathologists of
the consulted regional lymphoma board in the past, but had been rejected by the
board after external consultation.
PMID- 17036862
TI - [Partial resistance to acenocoumarol and phenprocoumon caused by enzyme
polymorphism].
AB - A 78-year-old man was treated with coumarin derivatives following myocardial
infarction. The international normalised ratio was not increased by using
standard loading doses and dose adjustments for acenocoumarol and phenprocoumon.
The desired level of anticoagulation was achieved with a high dosage of
phenprocoumon (18-21 mg daily). This dose was associated with a phenprocoumon
serum concentration that was ten times higher than the normal therapeutic
concentration. The serum concentration of vitamin K1 was low. After exclusion of
alternative causes, we concluded that the exceptionally high dose of
phenprocoumon needed was due to partial resistance to coumarin derivatives.
Partial resistance is related to a polymorphism of the gene coding for the enzyme
vitamin K epoxide reductase. The patient was successfully treated with chronic
high-dose phenprocoumon. Resistance to coumarin derivatives caused by a
congenital polymorphism in the vitamin K reductase gene is a rare phenomenon.
Resistance is seldom absolute. The desired anticoagulation effect can be achieved
with doses that are 10-20 times higher than standard doses. Phenprocoumon is
advantageous in this situation because it requires fewer tablets than
acenocoumarol. Determination of serum concentrations of acenocoumarol and
phenprocoumon can be used to exclude other causes of treatment resistance.
PMID- 17036864
TI - [Defining trials of medicinal products according to the revised Dutch Medical
Research in Human Subjects Act (WMO)].
AB - The revised Dutch Medical Research in Human Subjects Act (WMO), which implements
the European directive regarding 'good clinical practice in the conduct of
clinical trials on medicinal products for human use' (2001/20/EC), became
effective on March 1, 2006. The revision places additional requirements on trials
of medicinal products. Whether a trial should be regarded as a trial of a
medicinal product is therefore an important question. The law does not provide
adequate guidance for the classification of trials in which biological samples
are collected, e.g. for genomic, proteomic or pharmacokinetic studies, while a
medicinal product is given for a registered indication. Classifying these types
of trials as trials of medicinal products does not enhance the safety of the
participants. Therefore, these studies should not be considered as trials of
medicinal products to avoid the increased administrative burden required by the
revised WMO.
PMID- 17036865
TI - [A 26-year-old cyclist with intermittent claudication].
PMID- 17036866
TI - The big squeeze. Insurers point to slower growth in premiums in past few years to
show progress, but providers say they're paying the price.
AB - While insurers last week were trumpeting the third straight year of slower growth
in premiums, providers weren't exactly celebrating. That's because of huge
mergers, which give insurers far more leverage and have led to reimbursements
being cut back even more. "What's worrying us is that there's a growing segment
(of insurers) that aren't going to budge an inch, no matter what," says Russ
Weaver, left.
PMID- 17036867
TI - Measuring improvement. Performance standards, reporting save lives: NCQA.
PMID- 17036868
TI - Norwalk's CMS hurdles. Interim head faces Part D, reimbursement woes.
PMID- 17036869
TI - HRDI settlement near? Agreement likely to include payment concessions.
PMID- 17036870
TI - Tenet, HealthSouth clear some legal woes.
PMID- 17036871
TI - CHW settlement ups discounts.
PMID- 17036872
TI - Low scores, high costs. With waste and inefficiency rife, Americans need more
than HSAs.
PMID- 17036873
TI - Foreign exchange. CFOs in the U.K. seek greater collaboration between finance,
clinical teams as the National Health Service pursues reforms.
PMID- 17036874
TI - Out through the in door. Our annual Outsourcing Survey shows an uptick in
clientele as companies work to expand the array of services they offer.
PMID- 17036875
TI - Largest healthcare financing companies ranked by amount of loans underwritten
January through August 2006.
PMID- 17036876
TI - Is local A&E a thing of the past?
PMID- 17036877
TI - "Ageing Londoners deserve more focused healthcare".
PMID- 17036878
TI - "We can no longer blame the quality of hospital food for malnutrition in
hospitals".
PMID- 17036879
TI - Can nursing ever be stress free?
PMID- 17036880
TI - Keeping children safe from allergies. Interview by Janis Smy.
PMID- 17036881
TI - Combating a rising incidence of Legionnaire's disease.
AB - A statement released last week by the Health Protection Agency highlighted a
recent increase in the incidence of Legionnaire's disease in England and Wales.
Although an upsurge in cases is common at this time of year due to people
returning from holidays abroad, only a small proportion of the recent cases can
be attributed to foreign travel. Nurses need to be aware of the symptoms and what
health measures they can take.
PMID- 17036882
TI - Cricoid pressure.
PMID- 17036883
TI - Planning to improve the hospital experience for older inpatients.
AB - It is estimated that by 2031 the number of people aged 65 and over will exceed 15
million and comprise 23% of the whole population (Central Office of Information,
2006). This population shift will have dramatic effects on healthcare provision
and it is essential not only that the services are in place to meet this demand
but also that nurses have the skills to care for this age group.
PMID- 17036884
TI - Using audit to change practice for routine glucochecks.
AB - Glucochecks are commonly used on admission to hospital to pinpoint patients who
may have diabetes. This summary paper describes two clinical audits assessing
action following glucocheck results and staff education to improve follow-up. The
full audit paper can be accessed at nursingtimes.net.
PMID- 17036885
TI - Clinical decision-making and the nurse consultant role.
AB - This paper reviews the requirement for expert clinical decision-making in the
role of nurse consultants. The aim is to gain a better understanding of this role
by exploring the experiences and views of consultant practitioners. This is a
summary of the paper: the full version can be accessed at nursingtimes.net.
PMID- 17036886
TI - Implications of social enterprise for community nursing.
AB - Scott McAusland outlines the key points of the Queen's Nursing Institute briefing
paper Social Enterprise and argues that many clinicians need to develop business
and financial skills to take up social enterprise opportunities.
PMID- 17036887
TI - Managing infants with pyrexia.
AB - The management of pyrexia and fever is one of the most common childhood problems
faced by parents and health professionals, both in hospital and primary
healthcare settings. Cathy Taylor discusses the advice that should be offered to
parents. She identifies that the evidence base that supports this advise is
patchy.
PMID- 17036888
TI - Pneumococcal vaccine and the new child vaccination schedule.
AB - A vaccine to protect against pneumococcal infection is now offered to all UK
infants as part of the primary immunisation schedule. This, together with
modifications to the schedule for Haemophilus influenzae type b and meningococcal
C vaccines, represents the latest changes to the routine childhood immunisation
programme, which came into effect on 4 September. Helen Bedford and Laura Lane
outline why the pneumococcal vaccine has been introduced and the other changes to
the immunisation schedule.
PMID- 17036890
TI - Has the CMP become obsolete?
PMID- 17036889
TI - An overview of managing anaphylaxis in the community.
AB - Phil Jevon discusses the management of anaphylaxis in the community and the
national consensus guidelines on anaphylaxis (Project Team of the Resuscitation
Council UK, 2005).
PMID- 17036892
TI - [Dermatitis from the green lawn].
PMID- 17036894
TI - [Anorexia and bulimia. When food becomes the enemy].
PMID- 17036893
TI - [Without short acting insulin analogs. Is therapy quality really maintained?
(interview by Dirk Einecke)].
PMID- 17036895
TI - [Obesity time bomb. The fantasy land of plenty strikes back].
PMID- 17036896
TI - [New treatment method for incontinence (interview by Thomas Meissner)].
PMID- 17036897
TI - [Emergency rescue services cost a lot of money. However, no one pays for quality
control].
PMID- 17036898
TI - [Intensified insulin therapy. Is there an alternative to BE count?].
PMID- 17036899
TI - [Weight loss and recurrent erythema as a puzzle for physicians. Skin
manifestations came from the heart].
PMID- 17036900
TI - [Measure your patients blood pressure in all life situations. An elevated blood
pressure in the office is not hypertension].
PMID- 17036901
TI - [Blood pressure self measurement (BPSM)].
AB - Blood pressure self measurement (BPSM) offers advantages over measurements in the
doctor's office, and may improve the overall management of hypertension. BPSM
permits the identification of "white-coat hypertension" and "masked
hypertension". Longitudinal studies are needed to determine the true importance
of BPSM. Doctors must be aware of the strengths and weaknesses of BPSM and be
able to provide their patients with information about available devices for self
measurement, in particular about the accuracy and reliability of the devices they
are using. Patient training in blood pressure measurement should concentrate on
classification of blood pressure, blood pressure variability, standardized self
measurement, interpretation of the readings, and treatment of hypertension.
PMID- 17036902
TI - [Ambulatory long-term blood pressure measurement].
AB - Ambulatory 24-hour blood pressure measurement (ABPM) is a highly suitable method
for detecting nocturnal variations in blood pressure, early morning peaks and
unusual fluctuations during the course of the day. It enables an unequivocal
diagnostic work-up as also accurate treatment control. Moreover, the normal
values are lower than those measured during the occasional visits to the doctor's
office.
PMID- 17036903
TI - [Blood pressure measurement during ergometry].
AB - Blood pressure measurement during ergometry makes it possible to investigate the
blood pressure behavior during physical effort. It is considered an option for
the early detection of arterial hypertension, for the reliable investigation of
the efficacy of antihypertensive therapy also under conditions of effort, and for
the prognostic assessment of sequelae and cardiovascular events. The method is
simple and inexpensive, requires little expenditure of time, and produces readily
reproducible results. The submaximal workload range permits a ready
differentiation to be made between normotension and hypertension, while at the
same time, this workload range mimics everyday bodily effort, and, in principle,
can therefore be employed in all patients.
PMID- 17036904
TI - [Tilidine-Naloxone sustained-release tablets for chronic pain associated with
musculoskeletal disease].
PMID- 17036905
TI - [Diabetes mellitus and frequently associated endocrine diseases].
AB - The simultaneous occurrence of type 1 or type 2 diabetes with various hormonal
diseases (e.g. thyroid, adrenal, pituitary disease) is a frequent observation. A
chronically poorly controlled metabolism can alter the hormone parameters of the
diabetic. In contrast, an acute loss of metabolic control may be a sign of a
newly manifesting hormonal disease, and needs always prompt an appropriate
diagnostic work-up and treatment. In view of the frequency both of diabetes
mellitus and thyroid disease, a regular check--at least yearly and always in case
of unclear worsening of diabetic control--of thyroid gland function is mandatory.
The aim is to provide appropriate treatment, and thus to stabilize the patient's
metabolic status, as early as possible.
PMID- 17036906
TI - [Return of African sleeping sickness].
AB - At present there is a steady rise in African sleeping sickness (trypanosomiasis)
transmitted by the Tsetse fly, and which if left untreated, is fatal. Thanks to
more than so years of neglect by research, our therapeutic repertoire is limited
to medications with a high level of toxicity. Both WHO and international aid
organizations are pushing hard for the development of new, more efficient drugs
that can be readily applied in the field.
PMID- 17036907
TI - [Type 2 diabetes: hypoglycemia risk, weight gain... Will there soon be a new
alternative to insulin?].
PMID- 17036908
TI - [Therapy with incretin mimetic exenatide. Soon HbA1c value and weight decrease
permanently].
PMID- 17036909
TI - [Ambulatory treatment should soon be more independent. Good new--or bad news?].
PMID- 17036910
TI - [Reimbursement information is already in process. Despite this public health
insurance can still reclaim money].
PMID- 17036911
TI - [What would happen... if the physician were paid according to treatment
success?].
PMID- 17036912
TI - Disorders of calcium metabolism.
AB - Hypocalcaemia not associated with hypoalbuminaemia or 25(OH)-Vitamin D deficiency
is rare and should be referred to a specialist clinic. 25(OH)-Vitamin D
deficiency can often be treated safely by GPs, unless it is associated with renal
impairment and secondary hyperparathyroidism, in which case a nephrology referral
is required. An endocrine referral is required if deficiency is associated with
pregnancy, co-existent primary hyperparathyroidism or the patient is receiving
warfarin. The key role of the GP in managing hypercalcaemia is to distinguish
between malignant and parathyroid causes in order to make the appropriate
specialist referral (oncology, endocrine or renal). Severe hypercalcaemia
(greater than 3.5 mmol/L or hypercalcaemia with dehydration, abdominal pain or
reduced consciousness is a medical emergency.
PMID- 17036913
TI - Advising adults with type 1 diabetes.
PMID- 17036914
TI - How to detect growth disorders.
PMID- 17036915
TI - Cholesterol management.
PMID- 17036916
TI - Diagnose and treat hearing loss.
PMID- 17036918
TI - The MRCGP exam: an overview.
PMID- 17036917
TI - Manage urinary tract infections.
PMID- 17036919
TI - A guide to bacterial skin infections.
PMID- 17036920
TI - Anti-emetics, NSAIDs and opiates in migraine.
PMID- 17036922
TI - Genetic diversity and linkage disequilibrium in the Polynesian population of Niue
Island.
AB - Isolated populations that recently have been derived from small homogeneous
groups of founders should have low genetic diversity and high levels of linkage
disequilibrium and should be ideal for mapping ancestral polymorphisms that
influence complex genetic disease susceptibility. Populations that fulfill these
criteria have been difficult to identify. We have been looking for Polynesian
populations with these characteristics, because Polynesians have high rates of
complex genetic diseases. In Niue Islanders all ancestral female (mitochondrial
HSVI sequence) and 90.4% of ancestral male (Y-chromosome haplogroup) lineages are
of Southeast Asian origin. The frequency of European Y-chromosome haplogroups is
7.2%. The diversities of mitochondrial HSV1 sequences (h = 0.18 +/- 0.05) and Y
chromosome haplo-groups (h = 0.18 +/- 0.05) are lower than values published for
any other population. Ten autosomal microsatellites spaced over 5.8 cM show low
allele numbers in Niue Islanders relative to Europeans (55 vs. 88 total alleles,
respectively) and a modest reduction in heterozygous loci (0.71 +/- 0.02 vs. 0.78
+/- 0.02, p = 0.04). The higher linkage disequilibrium (d2) between these loci in
Niue Islanders relative to Europeans (p = 0.001) is negatively correlated (r =
0.47, p = 0.01) with genetic distance. In summary, Niue Islanders are genetically
isolated and have a homogeneous Southeast Asian ancestry. They have reduced
autosomal genetic diversity and high levels of linkage disequilibrium that are
consistent with the influence of genetic drift mechanisms, such as a founder
effect or bottlenecks. High-powered linkage disequilibrium studies designed to
map ancestral polymorphisms that influence complex genetic disease susceptibility
may be feasible in this population.
PMID- 17036923
TI - Association of genetic variation within UBL5 with phenotypes of metabolic
syndrome.
AB - The BEACON gene was initially identified using the differential display
polymerase chain reaction on hypothalamic mRNA samples collected from lean and
obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON
gene expression was positively correlated with percentage of body fat, and
intracerebroventricular infusion of the Beacon protein resulted in a dose
dependent increase in food intake and body weight. The human homolog of BEACON,
UBL5, is located on chromosome 19p in a region previously linked to quantitative
traits related to obesity. Our previous studies showed a statistically
significant association between UBL5 sequence variation and several obesity- and
diabetes-related quantitative physiological measures in Asian Indian and
Micronesian cohorts. Here we undertake a replication study in a Mexican American
cohort where the original linkage signal was first detected. We exhaustively
resequenced the complete gene plus the putative promoter region for genetic
variation in 55 individuals and identified five single nucleotide polymorphisms
(SNPs), one of which was novel. These SNPs were genotyped in a Mexican American
cohort of 900 individuals from 40 families. Using a quantitative trait linkage
disequilibrium test, we found significant associations between UBL5 genetic
variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations
of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals.
These data are consistent with our earlier published studies and further support
a functional role for the UBL5 gene in influencing physiological traits that
underpin the development of metabolic syndrome.
PMID- 17036924
TI - Body mass index and chronic energy deficiency of adult males of Central Indian
populations.
AB - Data on body weight, height, and sitting height from 11,496 adult males, age 18
62 years, belonging to 38 different populations of five major social groups
(scheduled tribes, scheduled castes, "other backward castes," general castes, and
Muslims) of Central India were taken for our analysis to assess the nutritional
status of these groups. Cormic index and body mass index (BMI) were computed, and
an analysis of variance (ANOVA) was carried out among different populations as
well as among social groups separately on Cormic index and BMI. Shape, size, and
generalized distances among the different social groups were computed and
dendrograms were drawn. The level of malnutrition is the lowest among the general
castes. The opposite is the case with the scheduled castes and scheduled tribes.
Comparison of the coefficient of variation shows that there is variation in
weight and BMI but that there is no marked variation in the other anthropometric
variables. The ANOVA on Cormic index and BMI suggests that the people within a
population are more homogeneous than the people between populations. There is a
positive but statistically insignificant correlation between Cormic index and
BMI. The five social groups differ more in size distance than in shape distance.
According to the dendrogram of generalized distance values, the Muslims and the
general castes can be grouped into one cluster and the scheduled castes,
scheduled tribes, and other backward castes can be grouped into another cluster.
PMID- 17036925
TI - Genetic variation at the mitochondrial DNA 9-bp repeat locus in the Sakha of
Siberia.
AB - Genetic variation at the mitochondrial DNA 9-bp repeat locus was assayed in 779
Sakha from Siberia. Fourteen deletion (1.8%), nine triplication (1.2%), and two 4
repeat alleles (0.26%) were identified. Several of these alleles were also
detected as heteroplasmies. Among the four heteroplasmic individuals identified
(0.51%), three different combinations of repeat alleles were present: 1/2, 2/3,
and 2/3/4 copies. Hypervariable region I (HVRI) sequencing revealed that three
different sets of haplogroups were associated with the three most frequent 9-bp
polymorphisms: (1) haplo-groups B, T, and W for deletions; (2) haplogroups C, D,
and K for triplications; and (3) haplogroups C, D, and T for heteroplasmies. Both
of the two 4-repeat alleles were associated with haplogroup D. We detected more
types of 9-bp polymorphisms and more genetic variation within classes of
polymorphism than previously reported for any single population. We also present
the largest and most geographically diverse sampling of the Sakha population to
date. No neighboring populations have been reported to carry a non-haplogroup B
deletion, triplication, or heteroplasmy, suggesting that shared ancestry or
admixture or both are unlikely explanations for the presence of these
polymorphisms in the Sakha. The identification of high levels of variation may be
a function of the large sample size and the in-depth analysis of all derived
polymorphisms. Further study of the Sakha is warranted to determine whether the
level of variation is unexpectedly high, especially in light of the presence of
different heteroplasmies, which suggests multiple recent events.
PMID- 17036926
TI - Genetics of dermatoglyphic asymmetry in Vaidyas of West Bengal, India.
AB - In this study of the genetics of dermatoglyphic asymmetry, we collected bilateral
finger and palm prints of 824 individuals from 200 families including 2
generations from an endogamous caste (Vaidya) in Barasat, North 24-Parganas
District, West Bengal. Two main types of asymmetry (fluctuating asymmetry and
directional asymmetry) were calculated between the two hands. The study includes
familial correlation between first-degree relatives, principal-components
analysis, and maximum-likelihood-based heritabilities (by pedigree analysis). We
found, first, that familial correlations in all possible pairs of relationships
(except spouse correlation) were weak but positive; some were even statistically
significant. No indication of assortative mating was observed, but the influence
of maternal environment could not be discarded. The results also showed that X
chromosome linkage does not seem to be involved. A second major finding is that
five principal factors could be extracted from all these asymmetric traits,
explaining 74.207% of the overall cumulative variance. Asymmetry of finger and
palmar areas were clearly separated by factor. In addition, the heritabilities of
the extracted five factors were in the range of 8-24%. These estimates are in
agreement with some previously published data. The heritabilities of the factors
describing palmar asymmetry are slightly lower than those describing finger
asymmetry. The present results support the hypothesis that both types of
asymmetry have a genetic basis and are influenced by the intrauterine
environment.
PMID- 17036927
TI - Frequencies of ABO, MNSs, and Duffy phenotypes among blood donors and malaria
patients from four Brazilian Amazon areas.
AB - We compared the serological phenotypic frequencies of ABO, MNSs, and Duffy in 417
blood donors and 309 malaria patients from four Brazilian Amazon areas. Our
results suggest no correlation between ABO phenotype and malaria infection in all
areas studied. We observed significant correlation between the S +s +, S +s -,
and S -s + phenotypes and malaria infection in three areas. Some of the Duffy
phenotypes showed significant correlation between donors and malaria patients in
different areas. These data are an additional contribution to the establishment
of differential host susceptibility to malaria.
PMID- 17036929
TI - ABO and Rh D polymorphism among Tibetans in India.
AB - A study of ABO and Rh D polymorphisms was conducted on 923 Tibetans living in
exile in four different places (both high and low altitudes) in India. The
frequencies of alleles p, q, and r for the ABO blood group system were found to
be 0.1295, 0.2544, and 0.6152, respectively, and for alleles D and d of the Rh
blood group system the allele frequencies were 0.9428 and 0.0572, respectively,
for the total data. No significant difference was found for the allele
frequencies among the four places for the two blood group systems. The allele
frequencies were in Hardy-Weinberg equilibrium for the ABO blood group system and
show East Asian affinity for the Tibetans.
PMID- 17036928
TI - Genetic heterogeneity among three Adi tribes of Arunachal Pradesh, India.
AB - We studied the distribution of ABO blood groups among three little known
subtribes of the Adi tribe, namely, the Panggi, Komkar, and Padam, of the East
and Upper Siang districts of Arunachal Pradesh, India. Blood group O was the
predominant group in the Komkar and Padam, whereas group A was the predominant
group in the Panggi. Blood group AB was found to be the least frequent group in
all three studied populations. The populations showed significant differences in
blood groups A (43% in Panggi, 23% in Komkar, and 18% in Padam) and O (33% in
Panggi, 54% in Komkar, and 61% in Padam). The chi-square test indicated
significant deviation from Hardy-Weinberg equilibrium, suggesting high
heterogeneity among the tribes.
PMID- 17036930
TI - CYP2A6 polymorphism reveals differences in Japan and the existence of a specific
variant in Ovambo and Turk populations.
AB - CYP2A6 is a polymorphic enzyme, and CYP2A6 genotype has been shown to be
associated with smoking habits and lung cancer. We investigated CYP2A6
polymorphism in Japanese from four different geographic areas of Japan and in the
Ovambo and Turk populations. Using two polymerase chain reaction restriction
fragment length polymorphisms (PCR-RFLPs), we identified the functionally
important variants of CYP2A6: *1A, *1B, *1F, *1G, *4A, and *4D. In the Japanese
population the highest frequencies of the CYP2A6*1A allele were observed in
subjects from the Fukuoka (Kyushu Island) and Ehime (Shikoku Island) prefectures,
whereas subjects in Shimane and Tottori (both located on the Japan Sea side of
Honshu Island) showed the highest frequencies of the CYP2A6*1B allele. In the
Tottori and Shimane groups no subject was homozygous for the CYP2A6*4A allele, a
whole gene deletion type that is prevalent among Asians. In the Ovambo and Turk
populations the CYP2A6*1A allele was predominant. Furthermore, two alleles
undetected in the Japanese were observed in these latter two ethnic groups:
CYP2A6*1G was found solely in the Ovambos, and CYP2A6*1F was found solely in the
Turks. The present study is the first to show interprefecture differences in
CYP2A6 polymorphism in Japanese who live in relatively close but distinct
geographic areas; this is also the first study to evaluate CYP2A6 variations
among these Japanese and the Ovambo and Turk populations. The distribution
results of these alleles could help to define the true significance of CYP2A6
polymorphism as a genetic susceptibility marker in worldwide populations.
PMID- 17036931
TI - Short tandem repeat polymorphism in the flanking region of the human
phosphoglycerate kinase gene in a Japanese population.
AB - The human phosphoglycerate kinase (PGK1) gene is located within Xqll-Xql3 and is
closely linked to the androgen receptor gene within a region implicated in a
number of X-chromosome-linked urologic disorders. A polymorphism of a TATC short
tandem repeat (STR) is present downstream from the PGK1 3' nuclease-sensitive
site. We present the PGK1 flanking STR sequence and population genetic data for
190 Japanese males and 83 Japanese females. Ten STR alleles and 29 genotypes were
identified in the population. Five alleles--*10, *11, *12, *13, and *14--were
common in the Japanese with frequencies greater than 10%. No significant
deviations from Hardy-Weinberg equilibrium were established. The power of
discrimination was 0.993 for females and 0.819 for males; heterozygosity was
0.759 for females; and the polymorphic information content was 0.936. These data
indicate that this STR locus shows a high degree of polymorphism in this Japanese
population and may prove to be a useful genetic marker in forensic medicine, in
determining the clonality of neoplasms, and potentially in studying
predisposition to prostate cancer and other urologic diseases.
PMID- 17036932
TI - Revolution in Massachusetts may spread to other states.
PMID- 17036933
TI - Specialty pharmacy grows as cost-control option.
PMID- 17036934
TI - Malpractice premiums constitute small component of expenses.
PMID- 17036935
TI - Managed Medicare revitalized. Feel-good plan of the decade.
PMID- 17036936
TI - Pharma tackles patient adherence.
PMID- 17036937
TI - PBMs raise the curtain.
PMID- 17036938
TI - We can't avoid tough decisions forever. Interview by Patrick Mullen.
PMID- 17036940
TI - Modest investment in 'coaching' seems to lead to lowered costs.
PMID- 17036941
TI - Remarkable work went into designing the new HPV vaccine.
PMID- 17036939
TI - Compliance with antithrombotic guidelines.
AB - Venous thromboembolism (VTE) remains a significant threat to public health
despite the availability of effective and safe prophylactic measures and
treatments. Guidelines based on randomized clinical trials are available to
improve the management of thromboembolic disease. However, gaps exist between
recommendations and clinical practice, and many patients are unnecessarily
exposed to the risk of a deep vein thrombosis or potentially fatal pulmonary
embolism. Barriers responsible for poor compliance with current antithrombotic
guidelines include lack of familiarity with recommendations, overestimation of
bleeding risk, underestimation of thrombotic risk, and logistical limitations of
health care management systems. Improving compliance is a complex task, but
successful initiatives rest upon improving thrombotic risk-assessment methods and
facilitating appropriate prescribing of prophylaxis. Multifaceted,
interdisciplinary strategies involving risk-assessment models, electronic
reminders, and audit and feedback show the most potential to improve compliance
with guidelines.
PMID- 17036942
TI - Payers, consumers benefit as patents expire.
PMID- 17036944
TI - [Histopathologic diagnosis in colorectal cancer screening: guidelines].
PMID- 17036943
TI - [Protocol for diagnostic assessment of sentinel lymph node in breast pathology: a
proposal of SIAPEC-IAP, Piemonte Region, Italy].
PMID- 17036945
TI - Myxoid tumor of soft tissue.
AB - Focal myxoid change is a well-recognised feature of synovial sarcoma, but the
presence of a predominantly myxoid stroma is rare. We describe a new case of
myxoid synovial sarcoma in which marked myxoid change initially obscured the
diagnosis leading to confusion with malignant peripheral nerve sheath tumor. The
patient was a 16 year old man who presented with a left dorsal foot tumor. The
diagnosis of synovial sarcoma was suspected on histological and
immunohistochemical studies and confirmed with cytogenetic analysis. Recognition
of this rare histologic variant of synovial sarcoma is important because it can
easily be mistaken for other myxoid spindle cell neoplasms, potentially resulting
in suboptimal therapy.
PMID- 17036946
TI - Syringocystadenoma papilliferum: report of 8 cases.
AB - Syringocystadenoma papilliferum (SCAP) is a rare cutaneous adnexal neoplasm with
variable clinical appearance and characteristic histology. It arises in about one
third of cases within a sebaceous hamartoma (SH) and in this case, multiple other
benign adnexal neoplasms may be associated with it. We report the clinical and
pathological data of 8 cases of syringocystadenoma papilliferum. The age at the
time of the diagnosis varied from 3 to 48 years with an average age of 28 years.
Three tumors were localized in the scalp, 2 in the trunk, and 3 others of unusual
locations: 1 in the eyelid, 1 in the thigh and 1 in the popliteal fossa.
Histopathological examination revealed 3 SCAP occurring within SH. The SCAP
observed in the eyelid was associated with an apocrine cystadenoma without
features of SH. The four others were not associated with any other lesion.
PMID- 17036947
TI - Sarcomatoid renal cell carcinoma in a young adult.
AB - Sarcomatoid renal cell carcinoma (SRCC) is an uncommon, aggressive renal cell
carcinoma (RCC) accounting for 1.2% to 12.3% of renal cell carcinomas. SRCC may
arise from any RCC subtype as it probably results from the de-differentiation of
any renal epithelial malignancy. SRCC is characterised by a rapid progression and
high metastatic rate. Currently there is no specific effective treatment for it.
We report a new case of a 32-year-old man presented with two months backache.
Ultrasound revealed a 7.5 cm heterogeneous mass at the inferior pole of the left
kidney. A nephrectomy was performed. Histological study diagnosed a sarcomatoid
renal cell carcinoma. The patient was doing well 6 months after initial surgery
and then was lost to follow-up.
PMID- 17036948
TI - [Ovarian oxyphilic Sertoli cell tumor: case report and review of the literature].
AB - Ovarian oxyphilic Sertoli cell tumor is a rare neoplasm (only three cases were
reported in literature). Sometimes the rarity itself of a lesion raises some
problem in the diagnostics, especially if the case is send to several
consultants. An unusual case of ovarian neoplasm came to our attention, and we
sent some slides of the case to two well known referees of different Departments
of Pathology. Pathologist 1 made a diagnosis of endometrioid adenocarcinoma,
while Pathologist 2 made the diagnosis of oxyphilic Sertoli cell tumor. He sends
the same slides to Pathologist 1, who confirmed his diagnosis. The two different
diagnosis set different managements of the lesion for the clinician, but overall
they set the pathologist who requested the consultation in a difficult position.
In fact, when a pathologist sends to two experienced consultants a case, he
really thinks to solve definitely the case itself. Unfortunately, sometimes it
does not happen.
PMID- 17036950
TI - [When old people fall].
PMID- 17036951
TI - [Complaints after meat meal: spoiled meat gotten?].
PMID- 17036949
TI - Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic
soft tissue: new entities and new variants of old entities recorded during the
last 25 years. Part XI: Excerpta IX.
PMID- 17036952
TI - [Stable coronary disease patients: more harm than benefit from heart catheter?].
PMID- 17036953
TI - [Heart catheter in angina pectoris: must we set stricter indications?].
PMID- 17036954
TI - [Old patient with atrial fibrillation: do you too hesitate to use
anticoagulants?].
PMID- 17036955
TI - [For prevention of cardiovascular diseases: statins in old age?].
PMID- 17036956
TI - [Dilemma of antihypertensive therapy: high blood pressure diminishes, potency
sometimes, too].
PMID- 17036957
TI - [Untrained, with heart disease, diabetic: who may go to the mountains?].
PMID- 17036958
TI - [Sunburn -- or yet not?].
PMID- 17036959
TI - [Whether the patient has heart or lung disease or diabetes, sport is the
cornerstone of therapy].
PMID- 17036960
TI - [The metabolic syndrome and sports].
AB - Lack of exercise and overweight are the causes of the metabolic syndrome (MTS),
which are currently acquiring almost epidemic proportions. Endurance training,
practiced alone or in combination with strength training, has a positive
influence on the insulin resistance that is at the heart of MTS. Endurance
training has a promoting effect in particular on the uptake of glucose by muscle
cells. Strength training reduces insulin resistance, and increases muscle mass
and, as a result, at the same time also the volume available for the uptake of
glucose from the blood. In addition, strength training also reduces visceral fat.
For the purpose of weight reduction in patients with MTS, the training-related
calorie consumption must be appreciably more than 2,000, and preferably should be
around 3000-3500 kcal/week.
PMID- 17036961
TI - [Chronic obstructive pulmonary disease and sports].
AB - From a moderate COPD onward, physical training is an essential component of
treatment. In recent years, it has become increasingly evident that endurance
training alone does not suffice to counter the progressive deconditioning
process. Since the muscular strength of COPD patients is significantly reduced
vis-a-vis healthy subjects, and this makes a considerable contribution to the
limitation of performance, functional health can be improved in particular by
adding strength training to endurance training. This applies all the more so
since a decrease in muscle mass is associated with a worsening of the prognosis.
In view of the fact that the ventilatory load is sometimes above the maximal
breathing capacity, training should be oriented to the patient's daily
requirements, in particular in advanced COPD. Furthermore, breathing and movement
techniques that spare the patient's resources should be taught.
PMID- 17036962
TI - [Physical activity in patients with renal insufficiency and patients on
dialysis].
AB - Regular exercise as a measure aimed at preventing renal failure results in a
positive influence on blood pressure, a reduction in weight, reduction in
peripheral insulin resistance, and a reduction in vessel rigidity.The same
applies to patients who already have renal failure. With regard to weight
reduction, however, it must be remembered that in the terminal stage of the
disease, an elevated BMI is associated with a higher life expectancy, since with
the need for dialysis a catabolic process with muscular atrophy and a loss of
stored fat begins. In this situation, the aim of physical activity is to help
reduce mortality in dialysis patients by improving cardiorespiratory function and
muscular strength, as well as their quality of life.
PMID- 17036963
TI - [Biologics in the treatment of psoriasis].
AB - Currently, psoriasis is seen as a T-cell-mediated autoimmune disease that is
characterized by an increased expression of pro-inflammatory cytokines. The
clarification of this pathogenetic cascade uncovered a number of points of
departure for the development of causal therapy and led to the introduction of
new medications--the so-called biologics. The following have already been
approved in Germany: infliximab, etanercept, efalizumab and adalimumab. These are
described, and their advantages and disadvantages in the clinical setting are
discussed.
PMID- 17036964
TI - [Suspected epilepsy: clarification of convulsions].
PMID- 17036965
TI - [Quality assurance in the medical practice: how well do we doctors really do our
work?].
PMID- 17036966
TI - [The electronic prescription and its consequences: physicians need waiting room
like a railroad station].
PMID- 17036967
TI - [Effect of angiotensin II on transforming growth factor beta-induced fibroblast
proliferation in human skin].
AB - OBJECTIVE: To observe the effect of angiotensin II (Ang II) or/and transforming
growth factor beta (TGF-beta) on human skin fibroblast proliferation, and to
explore the possible signaling mechanism involved in their actions. METHODS:
Cultured human skin fibroblasts were treated with different concentrations of Ang
II (1 x 10(-10), 1 x 10(-9), 1 x 10(-8) and 1 x 10(-7) mol/L) , TGF-beta(0.1, 1.0
and 10.0 ng/ml), and 1 x 10(-10) mol/L Ang II + 0.1 ng/ml TGF-beta, respectively.
The cell proliferation was determined by 3H-thymidine (3H-TdR) incorporation. The
phosphorylation of extracellular signal-regulated kinases (ERK) was detected by
Western blot. RESULTS: Ang II at 1 x 10(-9), 1 x 10(-8), 1 x 10(-7) mol/L or TGF
beta at 1.0, 10.0 ng/ml increased 3H-TdR incorporation into cultured skin
fibroblasts dose-dependently. Ang II and TGF-beta at lower doses (1 x 10(-10)
mol/L and 0.1 ng/ml, respectively) did not affect 3H-TdR incorporation into
fibroblasts (P>0.05), whereas co-administration of both Ang II and TGF-beta at
these doses significantly increased 3H-TdR incorporation into fibroblasts
(P<0.05). Ang II at 1 x 10(-7) mol/L or TGF-beta at 10.0 ng/ml significantly
increased ERK phosphorylation of fibroblasts after stimulation (P<0.01). Smaller
doses of Ang II (1 x 10(-10) mol/L) or TGF-beta (0.1 ng/ml) did not influence ERK
phosphorylation of fibroblasts, whereas co-administration of Ang II and TGF-beta
at these doses significantly enhanced ERK phosphorylation (P<0.05). Total protein
levels of ERK did not differ at different doses. CONCLUSION: These results
indicate that Ang II and TGF-beta synergistically increase skin fibroblast
proliferation, which is at least partly via enhancement of ERK activity.
PMID- 17036968
TI - [Influence of lipopolysaccharide on the biological characteristics of skin
fibroblasts and its potential role in wound healing].
AB - OBJECTIVE: To investigate the influence of lipopolysaccharide (LPS) on the
proliferation and collagen synthesis of normal human skin fibroblasts so as to
elucidate its relation with skin wound healing. METHODS: Fibroblasts were
isolated and cultured in vitro, and then exposed to different doses of LPS(0.005,
0.010, 0.050, 0.100, 0.500, and 1.000 microg/ml) from E. coli055:B5 respectively.
Then the absorbance (A) value of fibroblasts was determined with the
colorirneteric thiazolyl blue (MTT) assay, and the cell number was counted under
inverted phase contrast microscope from the 1st day to the 9th day after LPS
administration, and collagen synthesis of fibroblasts in culture medium was
measured with the method of pepsin digestion after incorporation of 3H-proline
into stable, single-layered, confluent fibroblasts at 7 days after LPS
administration. RESULTS: Compared with control group, A value increased with the
increasing concentration of LPS (0.005 microg/ml-0.500 microg/ml) and LPS of
0.100 microg/ml group had the strongest effect. The difference was remarkable
from the 5th day to the 9th day(P<0.05). A value decreased when challenged with
the LPS of 1.000 microg/ml and the difference was remarkable from the 3rd day to
the 9th day(P<0.05). Cell number increased with the administration of LPS of
different concentrations (0.005 microg/ml-0.500 microg/ml) and LPS of 0.100
microg/ml group had the strongest effect. The difference was remarkable from the
1st day to the 6th day(P<0.05). Cell number decreased remarkably when challenged
with LPS of 1.000 microg/ml and the difference was remarkable from the 2nd day to
the 9th day (P < 0.05). Collagen synthesis increased when challenged with LPS of
different concentrations (0.005 microg/ml-0.500 microg/ml) and the 0.100
microg/ml group had the strongest effect. However, when the dose of LPS reached
1.000 microg/ml, it inhibited collagen synthesis. CONCLUSION: LPS could promote
the proliferation and collagen synthesis of fibroblasts within a certain range of
low doses, but over-high dose of LPS might inhibit the proliferation and collagen
synthesis of fibroblasts, suggesting that LPS of certain concentrations might
contribute to wound healing, while excessive LPS has negative effect on wound
healing.
PMID- 17036969
TI - [Preliminary dissection of the blood supply on myocutaneous flap of rectus
abdominis on hypogastric zone].
AB - OBJECTIVE: To investigate the location of the artery correlated with rectus
abdominis musculocutaneous flap in order to promote the reconstruction of the
breast after radical mastectomy for breast cancer. METHODS: An anatomic study was
carried out on 15 cadavers of 30 sides, which were immersed in paraformaldehyde
less than six months. Whole thorax-epigastric wall was cutterd, which scale was
from subclavian as upper limit to inguinal ligament, the lower limit across left
and right of middle axillary. Veins or arteries of inferior epigastric and
internal thorax in hang were injected with red or blue ink to show all of vessel
branches. RESULTS: The external diameters of both the superior epigastric
arteries and inferior vessels were 1.87 +/- 0.28 mm and 2.25 +/- 0.32 mm
respectively. The myocutaneous arteries from inferior abdomen vessels had an
intensive horizontal distribution on hilum. The perforators significantly
decreased but could be found to pass through anterior rectus sheath in Rand. The
distances between lateral perforators and I , II and III parts in external edge
of anterior rectus sheath were 1.22, 1.46 and 1.57 cm, respectively; and the
distances between medial perforators and I, II, and III parts at median line were
1.54, 1.62, 1.66 cm. Perforators were more thick and intensive near hilum than in
other part. The subcostal arteries derived from inferior abdomen artery and 1.25
+/- 0.37 cm away from costal arch. After dividing into subcostal artery, the
outer diameter of 67 percent of subcostal artery was bigger than that of inferior
abdomen arteries. The branches of subcostal arteries were distributed at the 2/3
lateral rectus abdominis, forming an extensive choke anastomosis system with
intercostal anterior artery and vessels supplied diaphragmatic muscle. The rectus
abdominis at the level of xyphoid was supplied by a branch came from inferior
thorax artery, which diverged epigastric vessels at the same time. CONCLUSION:
During the process of making the inferior transverse rectus abdominis
musculocutaneous flap base on superior epigastric vessels and superior rectus
abdominis, reservation of pro-theca edge 1 cm of rectus abdominis can protect
inferior abdomen artery from injury. Reservation of more than 2 cm pro-theca and
rectus abdominis below costal arch at the flag will protect effectively subcostal
artery from injury. No damage of subcostal arteries can influence the survival of
musculocutaneous flap.
PMID- 17036970
TI - [Anatomic basis and clinical application of modified peroneal arterial cutaneous
branch nutritional flap].
AB - OBJECTIVE: To observe the anatomic basis and the clinical application of the
modified peroneal arterial cutaneous branch nutritional flap. METHODS: Twenty
sides of lower limb of adult colyseptic cadavers and 5 sides of lower limb of
adult fresh cadavers were used to detect the cutaneous branches of the peroneal
artery. The position where the cutaneous branches come from the peroneal artery
and the diameter of the cutaneous branches were recorded. From September 2003 to
June 2005, 10 cases of skin and soft tissue defects in the region of
metatarsophalangeal point with the modified peroneal arterial cutaneous branch
nutritional flap, in which the cutaneous branches from the peroneal artery 11.0
+/- 1.7 cm upon the lateral malleolus were added. The defect size was 10 cm x 6
cm to 15 cm x 10 cm. The flap size was 11.0 cm x 6.5 cm to 16.0 cm x 11.0 cm.
RESULTS: There is a stable cutaneous branches from peroneal artery 11.0 +/- 1.7
cm upon the lateral malleolus. The diameter of this cutaneous branches at the
origin is 1.45 +/- 0.12 mm. The distance between the cutaneous branches entrance
of the deep fascia and the line of the sural nerve nutritional artery flap was
15.70 +/- 1.20 mm. All 10 flaps survived. The blood supply and venous return of
the skin flaps were good. The 10 patients were followed up from 6 to 12 months.
The shape of the flaps was satisfactory. The texture and the color and luster of
the flaps were similar to the adjacent skin. The functions of the feet were good.
The two-point discrimination was 11-18 mm. CONCLUSION: The modified peroneal
arterial cutaneous branch nutritional flap has good blood supply. It can reverse
to a long distance and can repair large skin defects.
PMID- 17036971
TI - [Microsurgical anatomy of the facial nerve trunk in facial-hypoglossal nerve
anastomosis].
AB - OBJECTIVE: To study the microsurgical anatomy of the facial nerve (FN) trunk and
provide some important morphometric data about facial-hypoglossal nerve
anastomosis (FHA). METHODS: Bilateral microsurgical dissection was performed on
the heads of 9 cadavers fixed with formalin with three different methods. In the
first method, the posterior belly of the digastric muscle was used as a mark, and
the FN trunk was identified on the medial side of this muscle. In the second
method, dissection was initiated at the parotid gland, the FN trunk was
identified at its entrance into the parotid gland. In the third method, the
styloid process was identified and traced back to the stylomastoid foramen (SMF).
The FN trunk was identified on its emergence from the SMF. In every dissection,
the whole FN trunk was exposed; its diameter and depth at the the SMF and its
length were measured; its relationship, with other structures was studied.
RESULTS: The FN invariably emerged from the cranial base through the SMF. Its
diameter upon its emergence from the foramen was 2.57 +/- 0.60 mm. The mean
minimal distance of the FN trunk from the skin surface in this area was 22.62 +/-
2.88 mm. The length of the FN trunk was 15.71 +/- 1.97 mm. The distance between
the bifurcation and the mastoidale was 18.20 +/- 4.41 mm. The distance between
the bifurcation and the mandibular angle was 39.91 +/- 8.38 mm. The distance
between the mastoidale and the SMF was 17.91 +/- 2.68 mm. The branches from the
FN trunk proximal to its bifurcation were the posterior auricular nerve, the
digastric muscle nerve and the stylohyoid muscle nerve. CONCLUSION: The third
method to expose the FN trunk on its emergence from the SMF is safe and reliable.
It is feasible to use only part of the hypoglossal nerve fibers for anastomosis
with the FN trunk.
PMID- 17036972
TI - [Expanded clavipectoral skin flap combined with reverse axis skin flap in
repairing cervical scar contracture deformity after burn].
AB - OBJECTIVE: To evaluate the effect of a combined cervical expanded skin flap in
repairing cervical scar contracture deformity after burn injury. METHODS: From
April 2001 to May 2003, 16 cases (10 males and 6 females) of scar contracture
deformity in the cervix were treated with expanded clavipectoral axis skin flap
combined with reverse axis skin flap. The tissue expanders were embedded under
the part containing cutaneous branches of transverse cervical artery in cervical
segments and the second and/or the third perforating branch of internal thoracic
artery for the first operation. Normal saline was injected regularly. The
expanded clavipectoral skin flap and reverse axis skin flap with perforating
branch of internal thoracic artery were designed, the scar in the cervix was
loosed or dissected according to the size of the skin flaps, the skin flaps were
transferred to cover the wound, and the contracture deformity in the cervix was
corrected. The size of the flaps were 9 cm x 5 cm-15 cm x 7 cm. RESULTS: All skin
flap survived. The function and appearance of the cervix was improved
significantly after 6-30 months follow-up. However, venous return dysfunction in
reverse perforating branch of internal thoracic artery occurred in 1 case, and
blood circulation was improved after treatment. CONCLUSION: Expanded
clavipectoral axis skin flap combined with reverse axis skin flap can be used to
repair scar contracture deformity in cervix, which lessen scar and abate the
chance to contract again.
PMID- 17036973
TI - [Combined scapular/parascapular bilobar flaps for reconstruction of severe neck
contracture].
AB - OBJECTIVE: To discuss the reconstruction of severe neck contracture by
transplanting combined scapular/parascapular bilobar flaps, and the probability
to reestablish three-dimensional movement of the neck. METHODS: From January 2003
to November 2004, 9 cases of sustained severe neck contractures were treated
(aged 9-32 years). The combined scapular/parascapular bilobar flaps, pedicled on
the circumflex scapular vascular bundle, were microsurgically used to cover the
soft tissue defect after excision of hypertrophic scar and release of
contracture. The maximum size of the combined bilobar flap was 20 cm x 8 cm to 20
cm x 11 cm, while the minimum one was 15 cm x 4 cm to 15 cm x 6 cm. RESULTS: The
combined scapular/parascapular flaps were successfully used to treat 9 cases of
severe neck contracture. All patients were satisfied with the final functional
and aesthetic results. There was no recurrence during 3-9 months follow-up for 8
patients. The cervicomental angle was 90-105 degrees. CONCLUSION: The combined
bilobar scapular/parascapular flap, providing a large area of tissue for coverage
in three dimensions with a reliable blood supply by only one pedicle anastomosis
during operation, is a good option for reconstruction of the severe neck
contracture.
PMID- 17036974
TI - [Reconstruction of oral muco-defects with buccal fat pad flap].
AB - OBJECTIVE: To evaluate the clinical outcome of the buccal fat pad flap in
reconstruction of defects of the oral mucosa. METHODS: From May 1998 to July
2004, 42 patients with oral muco-defects were treated with buccal fat pad flap.
Of them, there were 26 males and 16 females, aging 25-76 years. The defect was
caused by buccal squamous carcinoma in 7 cases, by buccal leukoplakia in 5 cases,
by squamous carcinoma of soft palate in 7 cases, by adenoid cystic carcinoma of
palate in 8 cases, by carcinoma of maxillary sinus in 6 cases, by maxillo
alveolar angioma in 5 cases and by keratocyst of maxilla in 4 cases. The
locations were buccal mucosa, maxillary sinus and soft palate. The size of defect
ranged from 3.0 cm x 3.0 cm to 6.5 cm x 4.0 cm. RESULTS: Forty-one cases achieved
healing by first intention, except one case because of large defect. Edema faded
and epithelization occurred after 4 weeks of operation. Complete epithelization
was observed after 6 weeks of operation. Thirty-five cases were followed up 3
months to 5 years. There were no obvious differences in layers, color,
elasticity, and texture between repaired region and adjacent mucosa. CONCLUSION:
The buccal fat pad flap is useful in reconstructing the muco-defects (less than
6.5 cm in diameter) of the posterior maxilla and buccal region without
considerable complication. The multiplex blood supply, facility in accessing and
minimal donor site morbidity make it a reliable soft tissue graft. The main
shortcoming is its limited size.
PMID- 17036975
TI - [Modified transcranial approach to resect tumor around the anterior skull base
and double tissue flap to reconstruct the anterior skull base].
AB - OBJECTIVE: To explore better approach of resecting tumor around the anterior
skull base and reconstructing the anterior skull base. METHODS: In November 2004,
a 49-years-old male patient with intracranial recrudescent adenoid cystic
carcinoma in the anterior cranial fossa was treated using modified transcranial
approach. Neurosurgeon and rhinolaryngologist cooperated to excise the tumour
completely, and to reconstruct anterior skull base using the pedicle periosteum
temporal musculofascial flap (15 cm x 10 cm) and the pedicle flap of aponeurosis
of occipitofron tails muscle and muscular fasciae (10 cm x 6 cm). RESULTS: After
operation, the wound healed by first intention. Complication, such as infection
and cerebrospinal rhinorrhea, did not occur. The patient was discharged 10 days
after operation, and was followed up for 8 months, no local recurrence were
investigated and no scar formed over the face. CONCLUSION: The modified
transcranial approach is a relatively novel exposure that enables the skilled
cranial base surgeon to safely resect many malignant lesions previously and to
reconstruct the defect of anterior skull base together.
PMID- 17036976
TI - [Study on repair approach of bilateral cleft lips and nose deformity].
AB - OBJECTIVE: To detect the operative technique and aesthetic problem of
reconstruction to deformity of bilateral cleft lip. METHODS: From March 2003 to
December 2004, 26 patients with bilateral cleft lip were treated, aged 10 months
to 11 years. Of 26 patients, there were 13 bilateral complete cleft lip and
palate, 9 bilateral incomplete cleft lip and 4 mixed cleft lip with unilateral
complete cleft palate. The chief design principle was keeping the length of
prolabium. During operation, sufficient dissociation was made in the base of the
ala base and orbicularis oris muscle to reconstruct these structures. The circle
suture was made for the bilateral orbicularis oris muscle. The shape of vermilion
was achieved by lateral red lip muscle flap and simultaneous simple rhinoplasty
was performed. RESULTS: Primary healing of the incisions was achieved in all
cases. After the 10 days-3 months follow-up, the results were satisfactory in the
width and chubbiness of the nose bottom, the shapes of nostril and Cuspid's bow
were good without whistle deformity. The appearance of upper lip was good in
either dynamic or static state. CONCLUSION: Excellent shapes and function of the
nose and lip, and opportunity for two-stage repair could be obtained with this
method, which being believed important methods for the primary repair of
bilateral cleft lip.
PMID- 17036977
TI - [Clinical investigation of the combined therapy on deformed fingers after burn
injury].
AB - OBJECTIVE: To investigate the benefit of the combined therapy for deformed
fingers after burn injury by comparing with the conventional one, and to sum up
some experience. METHODS: From June 1999 to June 2004, 56 patients with deformed
fingers entered the trial. In 28 patients of treatment group who received
combined therapy (operation with post operational systematic convalescent care,
group A), there were 20 males and 8 females (14-47 years), 129 fingers of 47
hands were involved. In 28 of conventional group who received conventional
therapy (the same operational principle, and self-convalescent-care with out
patient service guidance, group B), there were 17 males and 11 females (18-51
years), 107 fingers of 42 hands were involved. Before and after the therapy, the
finger's motor function were assessed according to the Swanson method. The hand's
motor function was assessed through the Nine Hole Peg Test. RESULTS: The follow
up was 12-19 months in group A and 13-20 months in group B. The index of
ankylosis (IA) of group A before therapy was 82% +/- 20%, and 45% +/- 13% after
therapy; while the IA of group B before therapy was 78% +/- 17%, and 52% +/- 14%
after therapy. The decreased of IA between before therapy and after therapy was
37% +/- 15% in group A, and 26% +/- 15% in group B, showing significant
difference between the two groups (P<0.05). The Nine Hole Peg Test value of group
A was 28.34 +/- 5.62 s before therapy, and 20.73 +/- 4.25 s after therapy; while
that of group B was 27.47 +/- 5.78 s before therapy, and 21.86 +/- 4.12 s after
therapy. The decrease of the Nine Hole Peg Test value between before therapy and
after therapy was 7.61 +/- 2.27 s in group A, and 5.61 +/- 2.94 s in group B,
showing statistically significant difference (P<0.05). CONCLUSION: The combined
therapy is more effective than the conventional one.
PMID- 17036978
TI - [Thumb reconstruction with skin and soft tissue expansion].
AB - OBJECTIVE: To evaluate a new reconstruction method for grades V and VI defect
with flap by skin soft tissue expansion technique. METHODS: From May 1998 to
September 2003, 8 cases of serious thumb defect were treated, including 6 males
and 2 females, aging 18-27 years. The defect was caused by crush injury of
machine in 6 cases and hot crush injury in 2 cases (5 cases of grade V and 3
cases of grade VI). The expander was placed under the tenor skin and soft-tissue.
And then normal saline was infused to expand the skin and soft tissue gradually
till it was available for thumb reconstruction. Iliac autograft was fixed to
residual thumb stump and covered with flap produce by expanded skin and soft
tissue. Postoperative rehabilitation was carried out. RESULTS: All reconstructed
thumbs were alive. After 3-24 months follow-up, all reconstructed thumbs were
with good sensation, appearance and durable. Two-point discrimination was less
than 5 mm. The functions of opposition, extend, abduction and endoduction were
better in grade V thumb defect than in grade VI thumb defect. Bone union was
achieved within 3 to 4 months. CONCLUSION: It is a convenient-to-operate and
reliable method for thumb reconstruction. It is an alternative new reconstruction
method for grades V and VI, thumb defect.
PMID- 17036979
TI - [Combined treatment of refractory decubitus ulcers].
AB - OBJECTIVE: To summarize the clinical experience in the treatment of refractory
decubitus ulcers. METHODS: From May 1998 to March 2005, 22 patients with
decubitus ulcers (29 decubitus ulcers) were admitted, whose age was 36-92 years.
The lesion size was 4 cm x 2 cm to 18 cm x 15 cm. The locations of decubitus
ulcers were the sacrococcygeal region (18 cases), the tuber ischiadicus region (6
cases) and the trochanter major region (5 cases). Enteral nutrient was given
orally and the wound was treated with Wuhuangyihao 8-15 days. Three diabetic
patients were injected with insulin. According to patient's age, ulcer position,
ulcer extent and ulcer degree, the flap type was determined. Three wounds were
repaired by local flaps, the flap size was 6 cm x 4 cm-12 cm x 10 cm; 10 by
fasciocutaneous flaps, 10 cm x 7 cm-20 cm x 17 cm; 9 by gluteus maximus
myocutaneous flaps, 13 cm x 11 cm-17 cm x 14 cm; and 6 by long-head of biceps
femoris flaps, 11 cm x 6 cm-14 cm x 7 cm. One was sutured directly. After
operation, the patients were placed on airflow suspended bed 7-14 days. RESULTS:
General nutritional status was improved, hemoglobin was greater than 100 g/L,
albumen was greater than 30 g/L. Necrosis tissue was removed, granulation tissue
turned into fresh, secretion reduced and no redness and swelling occurred in
wound. All flaps survived and the wounds healed by first intention. After a
follow-up of 6 months to 5 years, no patient had a recurrence, the color and
texture of the flaps were good, the appearance was satisfactory. CONCLUSION:
Applying the technique of combined treatment can accelerate the healing of
refractory decubitus ulcers and improves the success of operation.
PMID- 17036980
TI - [Experimental study on magnesium phosphate cement in fracture treatment].
AB - OBJECTIVE: To investigate the effect of magnesium phosphate cement (MPC) to fix
fractures. METHODS: In vitro: fifty-four pairs of fresh pig femoral heads were
made 1 cm2 fracture and divided into 6 groups (n=9 pairs ). MPC was used to
agglutinate fracture of femoral heads at 100% humidity and at 25 degrees C, 37
degrees C respectively. At 30 minutes, 2 and 24 hours after agglutination, the
biomechanical strength was measured. In vivo: the tibia plateau fracture models
on both sides of 24 rabbits were made, one side was fixed with "L" shaped plate,
and the other side was fixed with MPC. Then the effect of treatment was
investigated by macrography, micrography, radiography and the In vitro: the
adhesive ability of changes of serum electrolyte levels at 3 days, 3, 6 and 9
weeks after operation. RESULTS: MPC was strong. At 24 hours after MPC
agglutination, the average tensile strength was 117.16 +/- 23.29 N/cm2. In vivo:
after 6 weeks of fixation, the X-ray results showed that all rabbits' tibia
plateau fractures were healed without displacement, and MPC was absorbed
gradually. The changes of serum electrolyte levels were very minimal. The
macrography observation showed that reduction of fracture were good at 3 days
after operation, partial MPC remained in fracture end at 3 weeks, fracture line
disappeared at 6 weeks and good remodeling was achieved at 9 weeks after
operation in the experimental group. The micrography observation showed that the
interface between bone and MPC was distinct at 3 days, MPC was degraded gradually
and trabeculae began to grow into MPC at 3 weeks, and almost all MPC was degraded
at 6 and 9 weeks of operation. CONCLUSION: MPC is a promising biomaterial, and
might potentially be used for fracture treatment.
PMID- 17036981
TI - [Experimental studies on the porous calcium phosphate cement combined with
recombinant human bone morphogenetic protein 2 for bone defects repair].
AB - OBJECTIVE: To study in vitro sustained release behaviour of the recombinant human
bone morphogenetic protein 2 (rhBMP-2) from the sample which porous calcium
phosphate cement (PCPC) was combined with rhBMP-2, and to evaluate the effect of
PCPC/rhBMP-2 composite on repairing bone defect in the animal study. METHODS:
rhBMP-2 was absorbed into PCPC by vacuum-adsorption and freeze-dried at -40
degrees C, the PCPC/rhBMP-2 enwrapped with chitosan as the experimental group,
the pure PCPC/rhBMP-2 as the control group, then the sustained release of rhBMP-2
from PCPC was determined in simulated body fluid (SBF) by UV-VIS
spectrophotometer. At same time, the PCPC/rhBMP-2 composites with chitosan were
implanted into the (4.2 mm x 5.0 mm femora defects of rabbits, which were
considered as the experimental group, whereas in the control group only PCPC was
implanted. The effect of repairing bone defect was evaluated in the 4th and 8th
week postoperatively by radiograph and histomorphology. RESULTS: The PCPC have a
high absorption efficiency to rhBMP-2, and the release of rhBMP-2 was sustained
release system. The release of rhBMP-2 from PCPC in the experimental group (99%
after 350 hours) was slower than that in the control group (100% after 150
hours). In the experimental group, the radiological and histomorphological
evaluations showed that the interfaces between the materials and host bones
became blurred both at 4th and 8th week. The implanted materials were partially
absorbed, and the implanted areas exhibited the formation of new bone. In the
control group, a little amount of new bones was observed. CONCLUSION: The PCPC
shows great clinical potential as a carrier for rhBMP-2. The PCPC/rhBMP-2
composite possesses much potentialities of osteoinductivity and the ability of
repairing bone defect, so it can be used as a novel bone substitute clinically.
PMID- 17036982
TI - [Preparation of gentamicin-impregnated bone allograft and experimental study on
treatment of infective bone defect].
AB - OBJECTIVE: To study and prepare a new kind of bone graft, which has osteogenesis,
local anti-infective function and low immunogenicity. METHODS: Gentamicin
impregnated bone was prepared by means of ultrasonic and vacuum, the release of
gentamicin in vivo was measured by inhibition bacteria. Ten healthy male adult
sheep were made animal infection models of thigh bone or humerus defect of 6 mm x
6 mm x 20 mm at size, and the defect was inoculated into 1 ml 5 x 10(10) CFU/ml
Staphylococcus aureus. The animals were randomly divided into the experimental
group (n=5, the bone graft with gentamicin was implanted) and the control group
(n=5, the bone graft without gentamicin). Macroscopic, WBC count, radiological,
and histological investigations were carried out to evaluate the anti-infective
and osteosis capability. RESULTS: The concentrations of gentamicin were 46.1
microg/ml in bone allograft and 17.3 microg/ml in muscles after 1 day. The
concentrations of gentamicin exceeding the minimum inhibitory concentration
lasted for 14 days in vivo. WBC in the control group was higher than that in the
experimental group. In the control group, 1 case died owing to septicemia 3 weeks
after operation. The implanted bones were wrapped in pus 4 and 6 weeks, and the
defects were filled with fibre tissue 8 and 10 weeks after operation. In the
experimental group, 1 case was infected, the others had a good concrescence. The
bone allografts began to integrate with adjacent bone after 4-8 weeks and
integrate well after 12 weeks. The X-ray and histological observation showed that
new bone formed and took the place of bone allograft. CONCLUSION: The gentamicin
impregnated bone allograft was of a good sustained release feature in vivo, local
anti-infection and osteogenesis. It might be an ideal bone grafting material for
bone defects with infection.
PMID- 17036983
TI - [Assessment of therapeutic results for simple bone cyst with percutaneous
injection of autogenous bone marrow].
AB - OBJECTIVE: To evaluate the therapeutic results of percutaneous injection of
autogenous bone marrow for simple bone cyst and to analyze the prognostic factors
of the treatment. METHODS: From March 2000 to June 2005, 31 patients with simple
bone cysts were treated by percutaneous injection of autogenous bone marrow. Of
31 patients, there were 18 males and 13 females, aged 5 years and 7 months to 15
years. The locations were proximal humerus in 18 cases, proximal femur in 7 cases
and other sites in 6 cases. Two cases were treated with repeated injections. The
operative process included percutaneous aspiration of fluid in the bone cysts and
injection of autogenous bone marrow aspirated from posterior superior iliac
spine. The mean volume of marrow injected was 40 ml (30-70 ml). RESULTS: No
complications were noted during treatment. Thirty patients were followed for an
average of 2.2 years (1-5 years) with 2 cases out of follow-up. After one
injection of bone marrow, 9 cysts (29.0%) were healed up completely, 7 cysts
(22.6%) basically healed up, 13 cysts (41.9%) healed up partially and 2 (6.5%)
had no response. The satisfactory and effective rates were 67.7% and 93.5%
respectively. There was significant difference between active stage group and
resting stage group(P<0.05). There were no statistically significant difference
in therapeutic results between groups of different ages, lesion sites or bone
marrow hyperplasia(P>0.05). CONCLUSION: Percutaneous injection of autogenous bone
marrow is a safe and effective method to treat simple bone cyst, but repeated
injections is necessary for some patients. The therapeutic results are better in
cysts at resting stage than those at active stage.
PMID- 17036984
TI - [Microsurgical treatment of arterial occlusion in lower extremity].
AB - OBJECTIVE: To investigate the procedure and clinical effect of revascularization
for arterial occlusion in lower extremity. METHODS: From July 1998 to March 2005,
29 cases of arterial occlusion were treated by microsurgery. Of 29 cases, there
22 males and 7 females, aging 22-86 years, including 9 cases of thromboangiitis
obliterans (TAO), 17 cases of arterial sclerosis obstruction (ASO) and 3 cases of
diabetic foot (DF). The location was the left in 17 cases, the right in 11 cases
and both sides in 1 case. All cases were inspected by color-Doppler ultrasonic
scanning before operation. The cases of ASO and DF were checked with MRA. The
results of examinations showed that the locations of arteriostenosis and
obstruction were: in 9 cases of TAO, the distal superficial femoral artery in 3
cases, popliteal artery in 5 cases, bilateral dorsal metatarsal artery in 1 case;
in 17 cases of ASO, common iliac artery in 2 cases, external iliac artery in 4
cases, femoral artery in 10 cases and popliteal artery in 1 case; and were all
superficial femoral artery in 3 cases of DF. DSA examination confirmed that there
was appropriate outflow in 15 cases. Basing on the location and extent of the
arterial occlusion, 11 cases were treated by the primary deep vein arterializing,
16 cases by arterial bypass distribution and 2 cases of extensive common iliac
arterial occlusion were amputated in the level of 1/3 distal thigh. RESULTS: The
postoperative duration of follow-up for all cases was 3 months to 7 years. In 9
cases of TAO, 2 healed by first intention after deterioration, 4 healed after
changing dressing and 3 had fresh soft tissue growth after debrided superficial
secondary necrosis. In 17 cases of ASO, 13 healed by first intention, 2 healed
after changing dressing and 2 were amputated. In 3 cases of DF, 2 healed after
changed dressing and debrided, 1 was aggravated with the second toe necrosis.
CONCLUSION: Performing primary deep vein-arterialization and arterial bypass
distribution is effective for treatment of arterial occlusion of lower extremity.
The arterial reconstructive patency rate can be improved by microsurgical
treatment.
PMID- 17036985
TI - [Vascularization in transplantation of gene modified tissue engineered bone for
repairing bone defect].
AB - OBJECTIVE: To study the vascularization of the composite of bone morphogenetic
protein 2 (BMP-2) gene transfected marrow mesenchymal stem cells (MSCs) and
biodegradable scaffolds in repairing bone defect. METHODS: Adenovirus vector
carrying BMP-2 (Ad-BMP-2) gene transfected MSCs and gene modified tissue
engineered bone was constructed. The 1.5 cm radial defect models were made on 60
rabbits, which were evenly divided into 4 groups randomly (n= 15, 30 sides).
Different materials were used in 4 groups: Ad-BMP-2 transfected MSCs plus PLA/PCL
(group A), Ad-Lacz transfected MSCs plus PLA/PCL (group B), MSCs plus PLA/PCL
(group C) and only PLA/PCL scaffolds (group D). The X-ray, capillary vessel ink
infusion, histology, TEM, VEGF expression and microvascular density counting
(MVD) were made 4, 8, and 12 weeks after operation. RESULTS: In group A after 4
weeks, foliated formed bones image was observed in the transplanted bones, new
vessels grew into the bones, the pores of scaffolds were filled with cartilage
callus, osteoblasts with active function grew around the microvessels, and VEGF
expression and the number of microvessels were significantly superior to those of
other groups, showing statistically significant difference (P<0.01); after 8
weeks, increasingly more new bones grew in the transplanted bones, microvessels
distended and connected with each other, cartilage callus changed into trabecular
bones; after 12 weeks, lamellar bone became successive, marrow cavity
recanalized, microvessels showed orderly longitudinal arrangement. In groups B
and C, the capability of bone formation was weak, the regeneration of blood
vessels was slow, after 12 weeks, defects were mostly repaired, microvessels grew
among the new trabecular bones. In group D, few new vessels were observed at each
time, after 12 weeks, broken ends became hardened, the defected area was filled
with fibrous tissue. CONCLUSION: BMP-2 gene therapy, by up-regulating VEGF
expression, indirectly induces vascularization of grafts, promotes the living of
seed cells, and thus accelerates new bone formation.
PMID- 17036986
TI - [Proliferative effect of basic fibroblast growth factor and epidermal growth
factor on muscle derived stem cells].
AB - OBJECTIVE: To explore the effect of basic fibroblast growth factor (bFGF) and
epidermal growth factor (EGF) on the growth of muscle derived stem cells (MDSCs).
METHODS: MDSCs were isolated from hindlimb muscle of 15 new born Kunming mice
through serial preplates. 2% fetal bovine serum-containing DMEM was used to
induce MDSCs to differentiate into skeletal muscle lineage. The expressions of
stem cell marker Sca-1 and skeletal muscle cell marker alpha-Sarcomeric actin
were examined by immunocytochemistry. The effect of bFGF and EGF on the
proliferation of MDSCs was determined by MTT colorimetric microassay. The solo
effect of bFGF or EGF at different concentrations (6.25, 12.50, 25.00, 50.00, and
100.00 ng/ml) was examined at 96 h and the combined effect (100.00 ng/ml) was
examined at 24, 48, 72 and 96 h. RESULTS: MDSCs were successfully isolated from
the hindlimb of neonatal mice. Over 90% of MDSCs showed Sca-1 positive
immunoreactivity. MDSCs could give rise to alpha-Sarcomeric actin positive
myotubes in differentiation cultures. The proliferative effect of bFGF and EGF on
MDSCs increased with the elevated concentration. bFGF began to show significant
proliferative effect at 12.50 ng/ml (P<0.05). The effect increased significantly
when the concentration reached 25.00 ng/ml from 12.50 ng/ml (P < 0.01) and
reached a saturation point. The effect at 50.00 ng/ml or 100.00 ng/ml showed no
significant increase when compared with that at 25.00 ng/ml. EGF had a similar
effect to bFGF except that the saturation concentration was 50.00 ng/ml. EGF
showed significant effect at 72 h and bFGF at 96 h (P<0.01). When they were
applied together, significant effect was shown at 24 h (P<0.01) and much higher
effect was observed at 48, 72 and 96 h (P<0.05). CONCLUSION: Both bFGF and EGF
can promote the proliferation of MDSCs. The combined application reacts faster
and stronger.
PMID- 17036987
TI - [Experimental study on transforming growth factor beta3 gene transfecting into
marrow mesenchymal stem cells in rabbits].
AB - OBJECTIVE: To construct recombinant adenovirus vector containing human
transforming growth factor beta 3 (TGF-beta3), which was transfected into marrow
mesenchymal stem cells (MSCs) and to observe its expression. METHODS: The cDNA
TGF-beta3 was integrated into the shuttle vector of pAdTrack-CMV and recombinated
with adenovirus skeleton vector pAdEasy-1 by homologous recombination. Then the
product was transfected into package cell HEK293 by lipofectamine and the
recombinant adenovirus expressing the TGF-beta3 gene was generated. The rabbit's
MSCs were isolated, cultivated, purified, and then transfected with recombinant
adenovirus containing the TGF-beta3 gene. The green fluorescence protein
expression was observed after 10 days, and the TGF-beta3 expression was observed
in MSCs transfected by recombinated adenovirus with TGF-beta3 gene after 4 days.
RESULTS: PCR showed that TGF-beta3 cDNA was inserted into the recombinant
adenoviral plasmid. The recombinant virus vectors with TGF-beta3 gene were
collected by the packaging HEK293 cells. The fusion rate of MSCs was 70%-80% with
an intensive adhesion and uniform shape after the cultured 10th day. Fluorescent
microscopy and immunocytochemistry demonstrated that TGF-beta3 was expressed in
MSCs. CONCLUSION: Successful construction of human TGF-beta3 recombinant
adenovirus and its expression in MSCs provide a basis of research for the gene
therapy of wound healing.
PMID- 17036988
TI - [Application of platelet-rich plasma in non-vascularized bone graft of
maxillofacial surgery].
AB - OBJECTIVE: To introduce the application of platelet-rich plasma (PRP) in non
vascularised bone grafts (NVBG) of maxillofacial surgery and its potential
mechanism in recent years. METHODS: The latest articles were extensively
retrieved, and the potential mechanism for PRP promotes the osteogenesis was
discussed. RESULTS: PRP promotes osteogenesis when applied to NVBG, and the
cytokine included in platelet is thought to be the ingredient for PRP's effect.
Some scholar has already applied PRP in the restoration of maxillofacial bone
defect and got good results. CONCLUSION: PRP has the potential to promotes
osteogenesis, and more studies are needed for further understanding of its
mechanism.
PMID- 17036989
TI - [Central projections of the rat superior laryngeal nerve].
AB - Laryngeal nerves contain the fibres that control the laryngeal function. On the
rat, the studies on the functional components and the real origin of the fibres
conveyed by the superior laryngeal nerve (SLN) are few. No one of such works were
developed using biotinylated dextrane amines (BDA), a powerful tool for tracing
neural pathways. The aim of our study was to identify by using BDA, in the rat,
the nuclei of real origin of the fibres of the SLN, knowing in this way the
functional components of this nerve. The study has been developed in 11 adult
male Sprague-Dawley rats, applying the BDA into the damaged SLN. The results
obtained in all the animals shown that the rat SLN carries efferent fibres
originated within the ipsilateral nucleus ambiguous (NA) and dorsal nucleus of
the vagus (DNV), and that afferent fibres reach the tractus solitari and the
nucleus tractus solitari. So, in the rat, the SLN seems to convey efferent fibres
from the NA and DNV and, probably, all the laryngeal afferent fibres.
PMID- 17036990
TI - [Sensorineural hearing loss in cerebral palsy patients].
AB - INTRODUCTION: Cerebral palsy (CP) is the most common chronic motor disorder in
children and frequently associates sensorial pathology. The objective of our
study was to establish the prevalence and characteristics of sensorineural
hearing loss in children with CP. METHODS: We performed a retrospective study of
patients born between the years 1975 and 2004, diagnosed of CP in the "Marques de
Valdecilla" University Hospital. Clinical data were collected including the
presence of sensorineural hearing loss, age at diagnosis, treatment and
associated pathology. RESULTS: Sixty four patients had confirmed CP. Audiological
testing had been performed in thirty patients (47%) of them 18 (60%) had
sensorineural hearing loss (12 bilateral and 6 unilateral). In thirteen cases
hearing loss was associated with mental retardation. The age at diagnosis ranged
from 3 months to 7 years (mean 23.2 months). Eight patients were treated with
hearing aids and one with a cochlear implant. CONCLUSIONS: Sensorineural hearing
loss is frequent in CP patients. Management of this problem is difficult in this
setting because of the motor disorder and the associated pathology. Early
audiological assessment is very important to improve the language outcome in
these children.
PMID- 17036991
TI - [Assessment of hyperacusis: the self-rating questionnaire on hypersensitivity to
sound].
AB - BACKGROUND: Hyperacusis is a decreased sound tolerance. The audiological
examination includes the loudness discomfort level measurement and the handicap
evaluation, so we introduce the Spanish validation of the german sound
intolerance questionnaire. OBJECTIVES: To update the concept of hyperacusis and
to evaluate its handicap through a Spanish validation of the
Gerauschuberempfindlichkeit (GUF). PATIENTS: Forty patients referred to our
Tinnitus and Hyperacusis Clinic in the University Hospital, between October 2004
and February 2005. OUTCOME MEASURES: The Spanish version of the GUF was performed
after transla-tion and retro-translation. Internal consistency and reliability
were established. RESULTS: Spanish adaptation of the GUF and its subscales
(cognitive, somatic behaviour and emotional reaction) showed a high reliability
and internal consistency (Cronbach's alfa: 0.9007). Higher GUF scores were
statistically demonstrated in hyperacusis patients with hearing loss (p < 0.05)
or tinnitus (p < 0.05). CONCLUSIONS: Spanish adaptation of the GUF is valid,
reliable and can be used in a clinical setting to quantify the impact of
hyperacusis on patient's quality of life.
PMID- 17036992
TI - [Sentinel lymph node in tumors of the larynx: technique and results].
AB - OBJECTIVES: To evaluate the applicability of sentinel node biopsy in NO
carcinomas of the larynx. MATERIALS AND METHODS: We carried out a prospective
study in 19 patients with carcinoma of the larynx NO. We peritumorally infiltrate
with 1 mCi 99mTc-labeled nanocolloidal albumin via rigid endoscopy in general
anaesthesia. Sentinel node detection is performed with a gamma sonda during lymph
node detection. The histological results of the sentinel node are compared with
the excised neck dissection specimen. RESULTS: Identification of sentinel node
was successful in 17 patients (89.47%). In 11 patients the sentinel node was
tumor negative reflecting the correct neck lymph node status (pNO). Three
patients had metastases in the sentinel node. We observed three false- negative.
The sensitivity of the technique was 50% (3/6) and the negative predictive value
78.6%. CONCLUSIONS: We think that more studies are needed to use the technique in
the laryngeal cancer and that a correct selection of the patients is essential.
PMID- 17036993
TI - [Comparison of the results obtained through manual and automatic phonetogram].
AB - INTRODUCTION: The phonetogram (F) is the graphic representation of a person
phonatory potential. The F carried out with a sonometer and a frequency analyser
is what is called "manual phonetogram" (MPh), and the one obtained by means of a
computer is called the "automatic phonetogram" (APh). MATERIAL AND METHODS: We
have carried out in 12 lyrical singers a standard MPh and an APh with the program
Dr. Speech Science 3.0. RESULTS: It was showed a significant difference with a p
< 0.0005 in 14 of the 15 measures compared, and a p < 0.05 for the other one,
being in general the results of the automatic test different from those of the
manual in excess, with a correlation between the results obtained through both
methods. CONCLUSIONS: The APh obtained with the program Dr. Speech Science 3.0 is
a faster and easier way to obtain the phonetogram than the one used to obtain the
MPh, showing however big differences in excess compared with the ones of the MPh
in all the usual phonetometric parameters.
PMID- 17036994
TI - [Qualitative spectral evaluation of oesophagic voice].
AB - OBJECTIVES: The aim of the study is to determine the accuracy of acoustic
spectrography as an outstanding tool in the characterization and monitoring of
esophageal voice. MATERIAL AND METHODS: Our subjects were comprised of 33
laryngectomized patients (all male) that underwent qualitative acoustic
(spectrography of vowel /a/ and a sentence), quantitative acoustic (phonation
time, fundamental frequency, maximun intensity sound level, speech rate) and
perceptual protocol. RESULTS: There is a significant statistical relationship
among Yanagihara-like spectrographic chart classification, psycho-acoustical
perception and quantitative acoustic parameters. CONCLUSION: We consider that
acoustic spectrography is an easy, effective method for studying esophageal
voice, seeking for improving oral communication skills and rehabilitation in the
laryngectomee population.
PMID- 17036996
TI - [Ear print as an identification method].
AB - In recent years, the analysis of earprints has been developed in the field of
legal and forensic medicine, with the aim of acquiring an identification tool
similar to fingerprints. In the present paper, we review the current status of
earprint identification from both a medical and a legal perspective. The
objective is to introduce an area of knowledge which, is spite of its closeness,
is not familiar to otolaryngologists, and to present the up to date scientific
evidence. First, identification in general, and earprint analysis in particular,
are situated in a historical context. Second, an approximation is made to the
complexity of earprint analysis, introducing conceptual problems of the method,
and possible solutions. Next, a discussion on the legal peculiarities of the
validity of the method is undertaken from the forensic point of view, and
finally, current development is pointed.
PMID- 17036995
TI - [Deep neck infections: etiology, bacteriology and treatment].
AB - Deep neck infections are dangerous for its potential ease to fascial spread,
sepsis, and upper airway obstruction. This article reviews 77 cases of deep
cervical infection, focus on etiological, clinical and therapeutic aspects. The
most frequent location was the submaxillary area (29%), followed by the
parapharyngeal space (28%), floor of the mouth (27%) and retropharyngeal (14%)
spaces. Etiology was dental in 32%; pharyngoamigdalar infection in 27%; foreign
bodies in 13%. In 22% the cause is unknown. Two or more bacteria were isolated in
72%, with Streptococcus B haemolytic being the most frequent germ. All patients
were treated with intravenous broad-spectrum antibiotics. Surgical drainage was
needed in 54%, and tracheotomy in 18%. Four patients developed mediastinitis, and
one died as a consequence of it. The incidence of deep neck infections has
decreased after the itroduction of antibiotics but they still may be lethal
especially when life-threatening complications occur. Early recognition and
management are necessary.
PMID- 17036997
TI - [Auditory neuropathy due to the Q829X mutation in the gene encoding otoferlin
(OTOF) in an infant screened for newborn hearing impairment].
AB - We report an infant with auditory neuropathy secondary to the Q829X mutation in
the gene encoding otoferlin (OTOF). Included in a universal newborn hearing
screening program, the subject passed the otoacoustic emission (OAEs) test. Given
that the infant had a familial history of deafness auditory brainstem response
(ABR) testing was performed, revealing a profound hearing impairment. The genetic
study confirmed that the subject was homozygous for the Q829X mutation in OTOF.
The patient underwent a cochlear implant, obtaining satisfactory results. The
moderately high prevalence of this mutation in the Spanish population could
produce a significant false negative rate in newborn hearing screening programs
using OAEs.
PMID- 17036998
TI - [Temporal bone chondroblastoma. A clinical case and literature review].
AB - We report a clinical case of a 31 year old male with a left temporal painful mass
of six months evolution. After radiologic diagnosis, intraoperatory biopsy and
surgical removal, the anatomopathological result confirmed the histology of
chondroblatoma, with a satisfactory postoperative evolution. The chondroblastoma
is a benign bone tumor typically located in the epiphysis of long bones and the
temporal bone is an excepcional location as we have verified through a literature
review.
PMID- 17036999
TI - Translational medicine in ultra-long injectable opioid drug discovery--when abuse
liability and toxicity meet analgesic efficacy.
PMID- 17037000
TI - Correlations between patient-controlled epidural analgesia requirements and
individual characteristics among gynecologic patients.
AB - BACKGROUND: Patient-controlled epidural analgesia (PCEA) has been used widely to
relieve postoperative pain. Although many studies have demonstrated the safety
and effectiveness of PCEA, the relationship between patients' characteristics and
requirements of PCEA has not been investigated yet. We conducted this
retrospective study to explore the correlations between total PCEA demand and
patients' characteristics. METHODS: We collected data from patients aged from 20
to 65, receiving gynecologic operations and consenting to epidural analgesia. All
patients used postoperative PCEA for at least 3 days. An analgesic solution of
bupivacaine (0.0625%) and morphine (0.02 mg/mL) was prepared for PCEA in all
patients. The total PCEA consumption was recorded at the end of the 3-day course.
Stepwise regression analysis was conducted to sort out influential factors which
could determine the total PCEA demand. RESULTS: There were 170 patients (81
benign and 89 malignant cases) included in the analysis. Significant differences
existed in age and total PCEA requirement between different disease patterns. The
stepwise regression model selection showed that disease patterns, body mass index
(BMI) and age were most significant determinants of total PCEA demand. The R and
adjusted R square values of the final selected model are 0.339 and 0.099,
respectively. The comparison between the standardized regression coefficient of
BMI and age suggested that the influence of BMI is greater than that of age.
CONCLUSIONS: Disease patterns, BMI and age are associated with total PCEA
requirements. Gynecologic patients receiving procedures for malignant diseases
consumed more PCEA solution than benign cases. Height is not associated with
total PCEA demand. There is a close correlation between BMI and PCEA consumption
but age is a negative correlate.
PMID- 17037001
TI - Nitric oxide scavenger carboxy-PTIO reduces infarct volume following permanent
focal ischemia.
AB - BACKGROUND: Nitric oxide (NO) has been shown to play a dual role as a
neuroprotectant and a neurotoxin in cerebral ischemia. Free radical scavengers
protect brain tissue from ischemic injury. Consequently, we examined the
neuroprotective action of NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5
tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), in cerebral ischemia
induced by permanent middle cerebral artery occlusion (MCAO) in rats and mice.
METHODS: All experiments were performed in a randomized fashion. In the first
series of experiments, adult Sprague-Dawley rats (n = 31) subjected to permanent
MCAO were treated with carboxy-PTIO (0.3, 0.6 mg/kg) or vehicle (normal saline)
injected intraperitoneally (IP) 1 hr before permanent MCAO. In the second series
of experiments, adult C57BL/6NCrj mice (n = 49) were treated with carboxy-PTIO
(0.6, 1.2 mg/kg) or vehicle saline 30 min following MCAO. Neurobehavioral scores
were determined 22-24 hr following permanent MCAO and infarct volumes determined
by quantitative image analysis of 2, 3, 5-triphenyltetrazolium (TTC)-stained
brain sections. RESULTS: Pre-treatment with carboxy-PTIO at 0.6 mg/kg IP in rats
significantly attenuated infarct volume (19.9 +/- 2.9%; n = 10) as compared with
vehicle-treated controls (29.2 +/- 2.7%; n = 16), but not at 0.3 mg/kg (28.3 +/-
8.4%; n = 5). Post-MCAO treatment in mice with 0.6 mg/kg carboxy-PTIO (30.3 +/-
3.9%; n = 16) significantly attenuated infarct volume as compared with vehicle
treated controls (46.1 +/- 2.8%; n = 18). CONCLUSIONS: These data demonstrate
that NO scavenger, carboxy-PTIO, provides significant ischemic neuroprotection
when given as a pre-treatment as well as after the onset of permanent focal
ischemia in two animal species.
PMID- 17037002
TI - Pain intensity and barometric pressure closely correlate in Southern Taiwan.
AB - BACKGROUND: Previous reports suggest that weather changes may affect the attack
and pattern of pain. However, a direct relationship between weather and pain
attack is yet to be determined, especially when very limited data are currently
available in the tropical or subtropical regions. METHODS: We studied the
patients who visited our clinic for pain management in Tainan, a city in southern
Taiwan, in the space from February 2004 to December 2005. Intensity of pain
measured by visual analogue scale (VAS) and the weather conditions including
temperature, barometric pressure, humidity and wind speed at the time of
measurement, were recorded. RESULTS: Our results indicate that higher scores of
the VAS were associated with older age and lower barometric pressure, while the
associations with temperature, humidity and wind speed were not statistically
significant. CONCLUSIONS: Our results demonstrate a unique pattern of pain, which
varies with barometric pressure, in the subtropical region and may provide
reference for better pain intervention during change of weather.
PMID- 17037003
TI - Comparison of intravenous patient-controlled analgesia with buprenorphine versus
morphine after lumbar spinal fusion--a prospective randomized clinical trial.
AB - BACKGROUND: Opioid-based patient-controlled analgesia (PCA) has been used widely
and effectively after spine surgery. The untoward effects of intravenous opioids
could vary with the drug and dose applied. Buprenorphine, a partial opioid
agonist, might be devoid of the adverse effects which the traditional opioids
have. We conducted this prospective randomized clinical trial to evaluate the
efficacy and safety of buprenorphine for intravenous PCA after spine surgery.
METHODS: Fifty patients undergoing elective lumbar spinal fusion were randomly
assigned to either buprenorphine or morphine group. PCA was administered in a
double-blind manner for a 2-day postoperative course. The evaluation was
initiated after patients were transferred to the post-anesthetic care unit. Pain
assessment with visual analog scale (VAS) at rest and after pain elicitation by
sitting was carried out and recorded at 6, 24, 48 hrs after surgery. Untoward
effects were also collected. RESULTS: Twenty-five patients were randomized to
each group. One patient in the buprenorphine group dropped out from the study due
to dizziness. There was no difference between the groups with respect to the
baseline variables. The VAS scores at rest and after elicitation of pain by
sitting showed no difference between both groups. The delivered volume of
buprenorphine, the numbers of demand and delivery, and the demand/delivery ratio
were higher in buprenorphine than morphine group at 6 hr after surgery but were
not different later. No major complications occurred in both groups. The pruritus
incidence in buprenorphine group was significantly lower than in morphine group
(0 vs. 24%, P = 0.02). Other adverse effects were similar in both groups.
CONCLUSIONS: Both buprenorphine and morphine by intravenous PCA provided adequate
pain relief after posterior lumbar spinal fusion. The incidences of side effects
were similar in both groups except for pruritus which did not appear in
buprenorphine group. Buprenorphine was as efficient as morphine and safe for
intravenous PCA after spine surgery.
PMID- 17037004
TI - The depot of buprenorphine decanoate produced a dose-related long-lasting
antinociceptive effect in guinea pigs.
AB - BACKGROUND: A long-acting analgesic may be particularly desirable in patients
suffering from long-lasting pain. The aim of the study was to evaluate the
antinociceptive effect of a novel depot of buprenorphine decanoate and its
metabolic profiles in human and animal blood. METHODS: Following their
intramuscular injections in guinea pigs, the antinociceptive effects of the novel
depot of buprenorphine decanoate (in oil) and the traditional dosage form of
buprenorphine HCl (in saline) were evaluated. An in vitro metabolic study of
buprenorphine decanoate in human and animal blood was also carried out. The
antinociception of drugs was evaluated using the plantar test. The blood
concentrations of drugs were assayed using a high performance liquid
chromatography. RESULTS: We found that both the buprenorphine HCl (in saline) and
buprenorphine decanoate (in oil) produced dose-related antinociceptive effect but
of different duration of action. Under an equi-mole basis of 0.6 micromol/kg, the
durations of action of buprenorphine HCl and decanoate were 4 and 72 h,
respectively. In in vitro metabolic study in human and animal bloods,
buprenorphine decanoate was totally converted to buprenorphine. Buprenorphine
decanoate is a prodrug of buprenorphine. CONCLUSIONS: Intramuscular injection of
the depot of buprenorphine decanoate in guinea pigs produced a dose-related long
lasting antinociceptive effect which was much longer than that of the traditional
dosage form of buprenorphine HCl. Moreover, buprenorphine decanoate is a prodrug
of buprenorphine.
PMID- 17037005
TI - The use of rocuronium and sevoflurane in acute intermittent porphyria--a case
report.
AB - Acute intermittent porphyria (AIP) is an inherited metabolic disorder caused by
deficiency of porphobilinogen deaminase, an enzyme found in the synthetic pathway
of heme. Acute attack of AIP may be precipitated by many factors during operation
and anesthesia, including fasting, dehydration, stress, infection, and drugs.
Acute attack of AIP is likely fatal. Therefore, the drugs recommended as being
safe in anesthesia for porphyria patients are up-to-dately refreshed and
renovated and the identification of whether a drug is safe or not is based on
cumulative anecdotal experiences. Here, we report the safe use of rocuronium and
sevoflurane for long exposure in a patient affected with acute intermittent
porphyria.
PMID- 17037006
TI - Combined subdural and epidural block in a case of epidural catheterization for
postoperative analgesia.
AB - We report a case of unusual block caused by postoperative epidural analgesia for
laparotomy in a gynecologic patient in consequence of inadvertent epidural
catheterization. The clinical manifestation included agitation, spotty
distribution of analgesia, wide spread of sensory block and loss of motor power.
The radiological findings suggested a multicompartmental block with the anchorage
of the catheter tip stretching over the epidural and subdural spaces. The default
of catheter position was not detected during routine test dose procedure.
PMID- 17037007
TI - Epidural analgesia masked the diagnosis of femoral neuropathy following renal
transplantation.
AB - Kidney transplantation related femoral neuropathy can mimic epidural catheter
related radiculopathy in clinical presentation. Anesthesiologists should keep
this possibility in mind when performing epidural anesthesia or analgesia for
kidney transplantation. We present a 52-year-old male who after undergoing
cadaveric kidney transplantation under general anesthesia in combination with
epidural analgesia made possible by catheterization via T11-12 interspace for
reinforcement of anesthesia and for postoperative patient-controlled epidural
analgesia (PCEA) sustained sensory disturbance and muscle weakness of the lower
limbs. These symptoms did not improve after discontinuation of the PCEA. Epidural
hematoma with secondary radiculopathy was contemplated initially. Serial
examinations including thoracic-lumbar CT scan, abdominal sonography,
electromyogram and nerve conduction study were thus performed. The final
diagnosis turned out to be surgical procedure related femoral neuropathy. We
believe this is the first instance ever reported about the dilemma in making a
predicative diagnosis from two conditions near akin in kidney transplantation.
Accurate diagnosis made through serial image and electrophysiologic studies are
essential to appropriate management.
PMID- 17037008
TI - Proper use of phosphodiesterase inhibitors according to the situations.
AB - We came across a case who because of sustained hypotension with normal cardiac
output was given amrinone which offered an initial excellent response but showed
impotency later and its replacement by milrinone dramatically improved the
hemodynamic status. The ensuing hypotension was thought to be the consequence of
the use of amrinone which was given to treat hypotension in conjunction with
fluid therapy; besides, it also induced pulmonary hypertension. Therefore,
milrinone was given to replace amrinone and was successfully to turn the tide. It
is our suggestion that if the use of a phosphodiesterase (PDE) inhibitor is
indicated but its side effects are enhanced to refute its use, the application of
a different PDE inhibitor should be kept in mind.
PMID- 17037009
TI - Sevoflurane is safe for anesthetic management in patients with multiple
sclerosis.
AB - We report a safe anesthetic management of patients with multiple sclerosis (MS)
using sevoflurane. A 34-yr-old female patient with a 2-yr history of MS was
scheduled for gynecological surgery. Anesthesia was induced with propofol and
fentanyl and maintained with sevoflurane, nitrous oxide, and fentanyl. Vecuronium
was used for tracheal intubation. The patient showed rapid emergence from
anesthesia. Exacerbation of symptoms of MS was negative according to the
neurologic assessment at that time. Postoperative pain was managed mainly with
continuous venous infusion of fentanyl instead of neural block with local
anesthetics. Transient fever due to subcutaneous infection of the surgical site
was observed and topical drainage was required. Eventually, postoperative
exacerbation of symptoms of MS compared with preoperative status did not appear.
In conclusion, sevoflurane does not induce exacerbation of symptoms and
facilitates early postoperative neurologic assessment, therefore, it is one of
ideal anesthetics for MS patients.
PMID- 17037010
TI - [The value of multislice spiral CT in the diagnosis and staging of laryngeal
carcinoma].
AB - OBJECTIVE: To our knowledge, no date are available comparing the impact of
multislice spiral CT, and multiplanar reconstruction (MPR) and Virtual endoscopy
(VE) on pretherapeutic staging accuracy. The purpose of our study was to
determine which imaging should be used as an adjunct to other clinical
examinations in the pretherapeutic diagnosis and staging of laryngeal carcinoma.
METHOD: Thirty-two patients with laryngeal carcinoma who were treated surgically,
were prospectively underwent by contrast-enhanced multislice spiral CT, and MPR
and VE were subsequently done. CT slice thickness 5 mm, table feed was 5 mm, and
100 ml of intravenous contrast material was administered at a flow of 3.0 ml/s.
Two radiologists evaluated axial image and the combined image, the results were
studied in a blind way. UICCTNM stages were determined by the axial image
findings and the combined image findings of axial image, MPR, and VE, were
compared and correlated with postoperative pathology and microlaryngoscopy.
RESULT: In the evaluation of the neoplastic invasion of ventricular fold, vocal
cord, the anterior commissure, subglottic region,paraglottic space (PGS), pre
epiglottic space (PES), thyroid cartilage, and tissue beyond the larynx, the
combined images were better than axial images in accuracy (98.3% vs 91.3%, P <
0.01); The accuracy of the combined images staging was 81.3% and the accuracy of
axial image staging was 93.8%, the difference was not statistically significant
(P > 0.05). CONCLUSION: Axial image combined with subsequent MPR and VE could
improve the diagnosis in the evaluation of the neoplastic invasion, neither axial
image or the combined images could significantly improve pretherapeutic staging
of laryngeal carcinoma.
PMID- 17037011
TI - [The value of computed tomography scans of temporal bone and eustachian tubal
function tests for lesions at tympanic opening of eustachian tube in middle ear
cholesteatoma].
AB - OBJECTIVE: To investigate the value of high resolution computed tomography (HRCT)
of temporal bone and eustachian tubal function tests for lesions at tympanic
opening of eustachian tube in the patients of otitis media with cholesteatoma
prior to surgery. METHOD: The clinical data of 38 cases (41 ears) with
cholesteatoma, which were examined by HRCT scans and eustachian tubal function
tests before mastoidectomy (29 ears) or mastoidectomy+ tympanoplasty (12 ears),
were analyzed. RESULT: The rate of conformation between the radiographic and the
operative findings was 94.1% in the tympanic opening of eustachian tube. We found
that the rate of the process tissue in the tympanic opening of eustachian tube
was 86.5% (32/37) during the operation and that they were mainly granulation
tissues and cholesteatoma. The rate of eustachian tubal hypofunction was 90.2%
(37/41), the obstructive type and the incompetent type were 32 ears and five
ears, respectively, only four were normal. CONCLUSION: HRCT scans and eustachian
tubal function tests by Sonotubometry and Tubotymanoaerodynamic (TTAG) play vital
roles in diagnosis of the tympanic opening lesion of eustachian tube and in
assessment of eustachian tubal function pre-operation of middle ear
cholesteatoma.
PMID- 17037012
TI - [Analysis of mono-side sternohyoid myo-osteal flap used in reconstruction after
partial laryngectomy].
AB - OBJECTIVE: To evaluate the reconstruction effect and to investigate applied
indication of unilateral sternohyoid muscle flap with hyoid bone in laryngeal
carcinoma after partial laryngectomy. METHOD: Seventy-three identified cases have
been analysed by retrospective process. Statistic data mainly include
postoperative eating condition, decannulation rate and postoperative voice.
Detailed data of decannulation rate have been contrasted in different clinical
stages, clinical types and operation types of malignant tumor. More data include
three year, postoperative complications and so on. RESULT: There are about 79.5%
cases survived three years or more. All the cases can take food by mouth without
gastric tube after the operation, 12.9 days in average. The total decannulation
rate is 76.7% and difference is found between enlarged-vertical hemilaryngectomy
and the other types of operations. More than 83.6% patients can speak in a nearly
normal way. CONCLUSION: The decannulation rate, voice and swallowing function are
all recovered satisfactory after the reconstruction and the decannulation rate is
not influenced by clinical stage or else of laryngeal carcinoma, but only by the
range of ectomy. The mono-side sternohyoid muscle flap with hyoid bone can
restore a baggish defect of larynx, and the survival rate is satisfied. It can
take the place of full laryngectomy in some T3 or T4 cases whose extent of
disease laid particular emphasis on one side.
PMID- 17037013
TI - [Bilateral wedge-shaped cordectomy for treatment of bilateral vocal cord
paralysis].
AB - OBJECTIVE: A clinical evaluation of CO2 laser endoscopic bilateral posterior
wedge-shaped cordectomy (EBPC) in patients with severely compromised airway due
to bilateral paralysis of the vocal fold. METHOD: The CO2 laser EBPC was
performed in four cases of bilateral vocal cord paralysis. Follow-up has ranged
from five months to 36 months. RESULT: Three patients achieved satisfactory
airway after one laser procedure and one patient received second laser operation
to manage her posterior webbing. Final voice quality was subjectively good in all
patients. CONCLUSION: The authors' data confirm the safety, ease of performance,
and efficiency of the CO2 laser EBPC in patients with bilateral vocal fold
paralysis. The advantages of the procedure are simplicity in concept, reliability
of outcome, no need for prophylactic tracheotomy, low risk of complications,
adequate airway and good voice preservation. CO2 laser endoscopic bilateral
posterior wedge-shaped cordotomy is an alternative management option for relief
of upper airway obstruction due to bilateral vocal cord paralysis in abduction.
The procedure is worthy to apply in clinical use.
PMID- 17037014
TI - [Vocal sound study in supracricoid partial laryngectomy].
AB - OBJECTIVE: Vocal sound was studied in 21 patients underwent supracricoid partial
laryngectomy using Dr. Speech. METHOD: Vocal sound tests and frequency spectrum
analysis were used in 4 different approaches (CHEP, CHP, TCHEP, TCHP) both before
and after the operation. RESULT: Vibration pattern of new glottidis formed after
the four different operation approaches was approximately the same demonstrating
an augmentation of mucous membrane fluctuation. This vibration pattern were
increasing and stabilizing gradually with time. CONCLUSION: Retaining on both
sides and one side in supracricoid partial laryngectomy facilitates restoration
of vocal function.
PMID- 17037015
TI - [Cause and treatment of trachea cannula exodus after executed tracheotomy].
AB - OBJECTIVE: To explore the reason and correct management of trachea cannula exodus
in the patient who had been executed tracheotomy, and reduce the occurrence of
trachea cannula exodus and its complication. METHOD: To analysis retrospectively
23 cases of trachea cannula exodus after executed tracheotomy in patients who had
been obstructed in upper respiratory. RESULT: In 23 cases of trachea cannula
exodus, 21 cases were rescued succeeded, 1 case death, 1 case became plant man.
CONCLUSION: Occurrence of trachea cannula exodus after executed tracheotomy was
correlated with operative procedure, postoperative care and suitable selection of
tracheal cannula. Quick-witted ability of doctor and correct management is a key
that rescued succeeded.
PMID- 17037016
TI - [Arousal response in child patients in obstructive sleep apnea].
AB - OBJECTIVE: To analyze arousal response of Polysomnography (PSG) in children with
obstructive sleep apnea-hypopnea syndrome (OSAHS). METHOD: Fourty-eight children
with sleep disorder were studied with 32 guide Polysomnography and analyzed by
Polysmith. Sleep structure and arousals of preschool-aged and school-aged
children with OSAHS were compared with those of primary snore patients. RESULT:
The mean value of AHI of preschool aged children with OSAHS was (10.6+/-8.9) h,
of AI was (4.0+/-7.1) h, of HI was (6.6+/-4.6) h; The sleep structure between
OSAHS group and primary snore group was not significant (P > 0.05). The mean
value of ArI with AHI was (8.2+/-5.9) h, of ArI with LM was (19.6+/-5.8) h, whole
ArI was 49.3+/-20.4 in preschool-aged children with OSAHS; The mean value of ArI
with AHI was (7.6+/-6.3) h, of ArI with LM was (14.3+/-7.6) h, whole ArI was
49.9+/-14.9 in school-aged children with OSAHS. Those of OSAHS children were
higher than that of primary snore patients (P < 0.05). CONCLUSION: Although OSAHS
in children is characterized by a restless sleep, the structure is perfect and
mildly affected by OSAHS. The ArI with AHI, with LM and the whole ArI in OSAHS
children is higher than those of primary snore patients.
PMID- 17037017
TI - [The treatment for hypopharynx stenosis using platysma pedicle flap].
AB - OBJECTIVE: To evaluate the possibility and reliability of platysma pedicle flap
transfer in the correction of hypopharynx stenosis,and delineate the operation
skills and clinical results. METHOD: Ten patients with hypopharynx stenosis
underwent hypopharynx reconstruction using platysma pedicle flap. RESULT: Nine of
these patients had been decannulated successfully with good airway patency, good
pronunciation and a good swallow. CONCLUSION: Platysma pedicle flap transfer was
a single stage reconstruction, relatively simple procedure and less complication
that can restore an adequate airway and a good swallow. The results indicate that
the platysma pedicle flap is an ideal transplant for hypopharynx reconstruction.
This method is simple, safe and reliable.
PMID- 17037018
TI - [Study on anatomic measurement of oropharynx dimensions between OSAHS and the
healthy adults].
AB - OBJECTIVE: One was to study on anatomic measurement of oropharynx dimensions
between OSAHS and healthy adults, the other was to determine the normal value
range of the healthy adults oropharyngeal cavity. METHOD: Six anatomic
measurement of oropharynx dimensions were were measured among 200 healthy adults
and 93 adult patients with OSAHS,and were compared with that of healthy adults,
and to determine the normal value range of healthy adults oropharyngeal cavity.
RESULT: The oropharyngeal cavity size of OSAHS patients and healthy adults were
significantly different, P <0. 01. CONCLUSION: Nearly all OSAHS patients have
anatomic obstructive factors at oropharyngeal cavity, The normal valve range of
the oropharynx size can help to judge the oropharyngeal obstruction of OSAHS
patients, and to provide the standard date for the operation of UPPP.
PMID- 17037019
TI - [Clinical analysis of tracheobronchial foreign bodies in children in 1276 cases].
AB - OBJECTIVE: To investigate the effective therapy methods of foreign bodies in
respiratory tract to lower its complications and the mortality rate. METHOD:
Review the anesthesia methods, operation methods and therapeutic efficacy of 1276
cases of foreign body in respiratory tract and report three cases of death.
RESULT: Under total intravenous anesthesia we took out foreign bodies by
bronchoscope in 1197 cases and did that successfully for the first time in 1196
cases. Under aspiration anesthesia by ether we took out foreign bodies by
bronchoscope in 78 cases and did that successfully for the first time in 65
cases, we took foreign bodies for the second time in 12 cases. We carried out
tracheotomy in three cases. Edema of larynx was found in 12 cases among which 11
cases were under aspiration anesthesia by ether and one case was under total
intravenous anesthesia. Under total intravenous anesthesia, the longest time of
operation was 45 minutes, we could carry out the examination by bronchoscope for
five times and no edema of larynx was found in all cases. Under aspiration
anesthesia by ether, the longest time of operation was limited to 5 - 10 minutes,
we could carry out the examination by bronchoscope for three times at most;
otherwise, edema of larynx was very severe. Three cases died over apnea.
Mortality rate is about 0.24%. CONCLUSION: Total intravenous anesthesia combined
with surface anesthesia of respiratory tract mucosa is the ideal anesthesia
method for taking out foreign bodies in respiratory tract by bronchoscope. It is
more dangerous in cases that the foreign bodies are bean or that atelectasis is
found. We should notice that the less the patients are, the more dangerous the
operation is. In some cases tracheotomy is needed.
PMID- 17037020
TI - [The effect of the combined therapy on obstructive sleep apnea hypopnea
syndrome].
AB - OBJECTIVE: To study the effect of the combined therapy on obstructive sleep apnea
hypopnea syndrome (OSAHS) with radiofrequency ablation (RFA) and oral appliance
(OA), and to evaluate the side effect of oral appliances. METHOD: Twenty one
cases with OSAHS were selected to receive radiofrequency ablation or/and to wear
oral appliance according to obstructive site. Polysomnography (PSG) was used
before and after 3 months of treatment to evaluate the therapeutic effect. We
analyzed the lateral cephalogram and dental casts before initiating treatment and
after 14 - 24 months of treatment. RESULT: PSG studies confirmed improved
breathing parameters with the combined therapy. No skeletal changes in the
position of the mandible were noted, a alteration in the occlusion was found for
lifelong OSAHS treatment with an OA. CONCLUSION: This combined therapy is
effective for OSAHS, regular dental follow up visits are necessary when lifelong
OSAHS treatment with an OA is being considered for patients with OSAHS.
PMID- 17037021
TI - [Clinical study of tracheotomies children with juvenile onset recurrent
respiratory papillomatosis].
AB - OBJECTIVE: To analysis the clinical characteristics of tracheotomies children
with Juvenile-onset recurrent respiratory papillomatosis (JORRP) and to discuss
the time of decannulation. METHOD: Thirty-one children with JORRP, who underwent
tracheotomy and treated with CO2 laser in Otorhinolaryngology department of
Tongren Hospital between 1993 and 2005, were reviewed in this essay. We analysis
the age, the site of intratracheal papilloma, invasion fashion of lesion, et al.
RESULT: Thirty-one tracheotomies children underwent 32 tracheotomy, 20 cases was
decannulated. Among the 32 tracheotomies cases, three cases were decannulated in
1 month post operation and the intratracheal lesions were not found. There were
presented intratracheal lesions in 29 cases. Intratracheal lesions were not
presented in 20 cases after three months of decannulation. CONCLUSION: The
tracheotomy should strive to be avoided to JORRP patients. If a JORRP patient was
underwent tracheotomy, he should be decannulated as early as possible. The time
of decannulation was performed in the operation or post operation when the
intratracheal lesions was less.
PMID- 17037022
TI - [Fhit expression and its relationship with apoptosis and prognosis in nasal and
paranasal sinus carcinomas].
AB - OBJECTIVE: To assess the protein expression of Fhit and its correlation with
spontaneous apoptosis, tumor clinicopathological parameters and prognosis in
nasal and paranasal sinus carcinomas. METHOD: Forty-eight patients with NPSC
treated by radical operations from 1991 to 2000 were studied retrospectively.
Patients included 23 female and 25 male ranging in age from 20 to 71 years.
Spontaneous apoptotic cells were visualized by TUNEL accompanied by HE and PI
stain. Immunohistochemistry using SP method was used to assess the expression of
Fhit. RESULT: The loss of expression of Fhit was found in 26 patients (54.17%,
26/48). Comparing with abutting non-neoplastic tissue, reduced expression of Fhit
was found in 16 (16/29, 55.17%) patients. The adenoid cystic carcinoma showed
stronger expression of Fhit than squamous cell carcinomas (P <0.05). The
expression of Fhit correlated positively with apoptosis index (r = 0.379, P <
0.01). Patients with positive expression of Fhit had much better prognosis than
those with abnormal expression (P < 0.05). CONCLUSION: The reduced expression of
Fhit may be associated with carcinogenesis and prognosis of nasal and paranasal
sinus carcinomas. It could be the tumor suppressor gene and realize its function
through accelerating apoptosis in this kind of neoplasm. Fhit expression may
provide a novel predictive indicator for disease-free survival after surgical
resection and postoperative radiochemotherapy in nasal and paranasal sinus
carcinomas.
PMID- 17037023
TI - [Chemotherapy guidance of the drug sensitivity test in vitro in human laryngeal
squamous cell carcinoma].
AB - OBJECTIVE: Consequently, strong emphasis has been placed on finding appropriate
approach to achieve optimal treatment outcome. This study analyzed the drug
sensitivity of Hep-2 cells at concentration-dependent and time-dependent in
vitro. METHOD: Nonradioactive cell counting Kit-8 (Dojindo, Kumamoto, Japan) was
used to asses growth inhibition of cancer cells by 5-FU, Carboplatin and
paclitaxel (TXL) against each concentration and exposure time. We selected
optimal dose and administration regimen through comparing all the cure effect.
RESULT: The drug sensitivity test data revealed that 5-FU inhibited cell growth
dependently on concentration and time, that TXL did dependently on time, and that
Carboplatin did dependently on concentration. CONCLUSION: Dose and administration
methods both affect the treatment outcomes. So the drug sensitivity test in vitro
dose provide clinical therapy with the optimal dose and administration regimen.
PMID- 17037024
TI - Staffing, capacity, and ambulance diversion in emergency departments: United
States, 2003-04.
AB - OBJECTIVE: The increased demand for emergency department (ED) services over the
past decade has resulted in crowding. This report presents estimates of structure
and process characteristics of hospital EDs related to their capacity to treat
medical and surgical emergencies. Estimates of EDs experiencing crowded
conditions are also presented. METHODS: Several facility supplements were added
to the 2003-04 National Hospital Ambulatory Medical Care Survey (NHAMCS), which
were completed by hospital staff. NHAMCS samples nonfederal, short-stay, and
general hospitals in the United States. Of all sample hospitals that operated 24
hour EDs, 83 percent completed the supplemental questionnaires. Data from 467
hospitals were weighted to produce national annual estimates of ED
characteristics. RESULTS: There was an annual average of 4,500 EDs operating in
the United States during 2003 and 2004. Over one-half of EDs saw less than 20,000
patients annually, but 1 out of 10 had an annual visit volume of more than 50,000
patients. Although 16.1 percent of hospitals expanded their ED physical space
within the last 2 years, approximately one-third of others planned to do so
within the next 2 years. Most EDs used outside contracts to provide physicians
(64.7 percent). One-half of EDs in metropolitan statistical areas (MSAs) had more
than 5 percent of their nursing positions vacant. Of all on-call specialists, the
services of plastic and hand surgeons were most frequently reported as somewhat
or very difficult to obtain (49.4 percent). Approximately one-third of U.S.
hospitals reported going on ambulance diversion sometime in the previous year.
About 12 percent of hospitals in MSAs reported having spent between 5 and 19
percent of their operating time in diversion status. Between 40 and 50 percent of
U.S. hospitals experienced crowded conditions in the ED with almost two-thirds of
metropolitan EDs experiencing crowding.
PMID- 17037025
TI - [Experience with surgical treatment of lung cancer].
PMID- 17037026
TI - [Carcinogenic mechanisms and anticarcinogenesis].
PMID- 17037027
TI - [Use of hormone-replacement therapy and steroid contraceptives in menopause as an
oncological and epidemiological problem: is it a risk and/or benefit?].
PMID- 17037028
TI - [Dose fractionation for increasing the effectiveness of radiotherapy of tumors].
PMID- 17037029
TI - [Morbidity statistics of breast cancer in Moscow].
PMID- 17037030
TI - [Distribution of endometrial carcinoma in the city of Ufa (data from the
Bashkirian Oncology Dispensary)].
PMID- 17037031
TI - [Immediate and long-term results of plastic reconstruction of soft tissues of the
head and neck in areas previously treated with surgery for tumor and radiation
injury].
AB - The efficiency was studied of vascularized tissue complexes in 346 cancer
patients with extensive facial injuries to the head and neck who had undergone
combined treatment. Free microsurgical autotransplantation was carried out in 7
(2%) patients, deltapectoral graft--151 (44%), sternocleidomastoid myocutaneous
flap--39 (11%), pectoralis major flap--10 (3%), bi- and tri-lobed flap--55 (16%),
temporal musculoperiosteal flap--25 (7%), cheek flap--24 (6.9%), thoraco-dorsal
axillary flap--24 (6.9%), frontal flap--6 (1.7%), free-flap transfer--5 (1.5%).
Although most vascularized tissue complexes were placed in previously irradiated
areas, primary engraftment was reported in 249 (72%) patients, while peripheral
or partial necrosis in distal part of flap- in 97 (28%). Good cosmetic and
functional results were obtained in 298 (86%) patients who considered themselves
cured.
PMID- 17037032
TI - [Esophagoplasty using modified sleeve-type intrathoracic anastomosis].
AB - Anastomotic leakage due to loosening of sutures is the frequent cause of
lethality. To prevent such complication, a sleeve-type esophago-enteric and
esophagogastric anastomosis was used. Its design eliminates the major cause of
failure--the basic sutures running through the soft muscular wall of the
esophagus. The new anastomosis was used in ca. 42 patients: Lewis operation (24),
proximal resection of the stomach and distal thoracic part of the esophagus and
adjuvant intrapleural esophagoplasty with the distal end of the stomach (8),
gastrectomy with resection of the distal thoracic part of the esophagus and
concomitant intrapleural esophagoplasty with small intestine (S.S.Yudin) (10).
Postoperative complications were reported in 18 patients (42.9%); lethality-
11.9%. No leaking esophageal anastomosis was registered.
PMID- 17037033
TI - [Immunogenetic prognosis and long-term results of surgery for gastric cancer].
AB - A link between HLA allelic variants and long-term results of surgery for gastric
tumors was established on the basis of a 10-years follow-up of 112 cancer
patients (stage I-II--37.9, III-IV--62.1%; radical surgery--44.6%). HLA class I
was studied in a lymphocytotoxic test; HLA class II--gene DRBI specificity using
polymerase chain reaction of peripheral blood cell DNA. The control group
included healthy subjects living in the city of Novosibirsk (n = 341). High
frequency of antigens HLA-B41, -DR1, -DR7 (p < 0.01) co-occurred with HLA-A2,
B12, -B13 and -B18 presence (p < 0.05) in breast cancer patients. Clinical
manifestations of cancer were shown to develop in HLA-A1, -B8, -B15, -DR3 and
DR5 carriers at early stages. Tumor development at later stages (III-IV) was
associated with HLA-A2, -B12, -B17, -B35, -B41 and -DR7. A link was registered
between lethality rate, on the one hand, and HLA-A3, -B22, and, in particular,
DR4, on the other, while remission of more than 7-years--with HLA-A11, -B13, -B21
and -DR5. HLA-B22/DR3 phenotype involved worse prognosis in radically-treated
patients whereas that of HLA-B8/DR3--a better one.
PMID- 17037034
TI - [The use of roncoleukin for LAK therapy in ovarian cancer].
AB - Roncoleukin--recombinant IL-2--was studied with a view to application for LAK
therapy. Lymph of ductus thoracicus from ovarian cancer patients receiving
adjuvant autolymphochemotherapy was used as source of lymphocytes. Immunobiologic
activity of lymphocytes was assayed after 30-minutes incubation with roncoleukin
and 24- or 48-hours culturing. The investigation established an increase in T
cell proliferation, autocrine stimulation of IL-2 production, growth of NK-cells
cytotoxicity, immediate cytotoxic effect on K562 target cells culture and such
sensitizing effect as roncoleukin's potential to boost its susceptibility to NK
lysis. LAK-therapy was used as a component of complex treatment of ovarian cancer
(8). Our method has a future in dealing with the present pathology.
PMID- 17037035
TI - [Combined radiotherapy and endovascular x-ray therapy for invasive cancer of the
urinary bladder].
AB - The data are presented on treatment of 131 patients with transitional cell
carcinoma of the urinary bladder. Radiotherapy was received by 57, regional
intraarterial chemotherapy (RIAT)--27. Radiotherapy was combined with RIAT and
selective hyperglycemia (HG) in 18 cases. Local super high-frequency (SHF)
hyperthermia was given additionally to another 29 patients. Radiotherapy alone
was followed by primary clinical cure, a 9.6-months relapse-free period and 3
months survival (36.8%), mean survival time being 26 months. In the RIAT group,
these indices were 29.6%, 10.8 mos, 51.9% and 36 mos, respectively. Combination
of radiotherapy, RIAT and selective HG yielded significantly improved indices:
complete response--44.4%, relapse-free period--13.6 mos, 3-year survival--66.7%
and mean survival time--43 mos. After addition of SHF hyperthermia, complete
response rose to 69.0%, relapse-free period--18.2 mos, 3-year survival--75.8% and
mean survival time--61 mos. Joint use of radiotherapy, RIAT, HG and SHF
hyperthermia caused more damage to tumor, stimulated complete response and
increased 3-year survival and mean survival time.
PMID- 17037036
TI - [Effectiveness of repeated systematic radiotherapy for generalized prostate
cancer].
AB - Examination of 127 patients with generalized prostate cancer established a low
prophylactic effect of systematic treatment with strontium-39 chloride: it failed
to alleviate pain in metastatic cancer, nor was it followed by longer mean
survival. Repeat systematic radiotherapy is not indicated when palliative
measures such as hormonal therapy, local radiotherapy and chemotherapy are still
effective.
PMID- 17037037
TI - [Novel approaches to combination therapy of Hodgkin's disease].
AB - Data on 668 patients receiving 4-8 cycles of chemotherapy were used to suggest
the following approach to complex therapy of Hodgkin's disease: devise a
simplified model for Hodgkin's disease, develop a new modality of chemotherapy,
demonstrate feasibility of only four chemotherapy cycles in the poor prognosis
group, partial response as the ultimate goal of chemotherapy as well as the
importance of subtotal dosage under 26-36 Gy sufficient for irradiation of the
entire lymphatic collector. Said measures will, in their totality, offer fresh
opportunities in treatment of Hodgkin's disease.
PMID- 17037038
TI - [Effect of interleukin-2 on apoptosis and function of human lymphocytes in in
vitro cytostatics culture].
AB - In vitro experiments were conducted to determine the impact of interleukin-2 (IL
2) on apoptosis and function of cytostatic-cultured lymphoid (mononuclear) cells
(MNC) of peripheral blood from healthy subjects and children with cancer. Neither
slight or any effect on vepesid-16 or carboplatin--cultured MNC apoptosis, nor
any phytohemagglutinin--induced proliferation was found. By contrast, in
carboplatin- cultured MNC from healthy subjects, IL-2 significantly potentiated
their toxicity for tumor cells by producing interferon-gamma. It was concluded
that IL-2 predominantly supported MNC functional activity rather than inhibited
lymphoid MNC apoptosis in in vitro culture with cytostatic drugs.
PMID- 17037039
TI - [Psychological and immunological defenses in cancer--the two aspects of one
problem].
AB - The study group included 17 cancer patients, aged 25-55, (stage III-IV), mostly
suffering melanoma. All of them received hypnosuggestive therapy to correct
psycho-emotional disorders. Significant decrease in anxiety-related indices (p <
0.001) due to therapy pointed to rehabilitation of psychological defenses.
Clinical rehabilitation was manifested by improved quality of life (p < 0.01),
better habitus and adaptation (p < 0.01). The modulating effect on the
macrophageal and phagocytic components of the immune system (p < 0.05) was
matched by a significant correlation between psychological defense indices and
those of immunological status. Our data have contributed to the existing
knowledge about relationships of mind and immunity in cancer patients.
PMID- 17037040
TI - [Seasonal patterns of breast tumor growth in Far North residents].
AB - Earlier, we established a relationship between sex hormone receptor concentration
in tumor and 5-year survival, on the one hand, and seasonality, on the other. The
parameters showed a distinct 6-month cycle. That pointed to certain environmental
factors which could synchronize hormone-dependent tumor process in the breast of
women living in the North. The present study is concerned with a relationship of
6-month rhythm of tumor growth and latitude of residence. Said rhythm was
reliably identified as a parameter of 5-year survival in the Far North (68 deg.
northern latitude, p < 0.001). Maximum values of 5-year survival were registered
in those diagnosed with cancer in winter or summer, while those diagnosed in
spring or fall had unfavorable prognosis. Northern magnetic storms recur at 6
month intervals and most frequently in spring and fall. Electromagnetic radiation
is known to suppress melatonin production and, that might have stimulated tumor
process. Therefore, it is most likely that solar electromagnetic radiation might
synchronize hormone-dependent tumor process in women resident in the North.
PMID- 17037041
TI - [Antitumor immunity transfer by a factor isolated from lymphocytes of tumor
bearer].
AB - Low-molecular extracts (LMEs) of lymphocytes were obtained from spleen of
noninbred rats using our experimental model of intraorganic growth of Guerin's
carcinoma. They were intended to transfer immune reaction to tumor antigens in
vitro. It was LMEs developed prior to tumor progression in spleen that showed
immunospecific activity with respect to tumor cells. Also, they had marked
antigen-independent immunopharmacological activity. Single intravenous injection
of LMEs100 pg given on day 7 of tumor growth stimulated antitumor resistance in
intact rats within a short time. It prevented tumor cells engrafting in 60% of
tumors. A tumor-specific factor has been evolved capable of immune reaction
transfer to tumor antigens in vitro thus preventing tumorigenesis in recipients
in vivo.
PMID- 17037042
TI - [Thyroid cancer in male patients].
AB - Data on 117 male patients with thyroid cancer (1994-2004) have been assessed. It
was found that thyroid cancer often engenders in the nodular formation it males.
Early-stage cancers were detected in 63 cases (54.9%). Radiotherapy as a
component of combined treatment was the most popular modality (43.2%), due to the
malignant character of locally-advancer tumor. Ten-year survival was in 65.2%,
while, in 11.9%, radical surgery was not indicated.
PMID- 17037043
TI - [Endoscopic argon-plasma coagulation and combined radiotherapy for short (up to 3
cm) esophageal cancers].
AB - The immediate and 3-year results were evaluated of application of combined
radiotherapy and/or endoscopic argon-plasma coagulation carried out for
esophageal cancers 3 cm long or less in 39 patients. Recurrences were reported,
in 31.4% ca. 4 months later. Joint use of the modalities was followed by an up to
5-months rise in relapse-free period. Mean survival time was 20.2 months, and it
was significantly higher in radiation-treated patients without metastases. One
year survival was 96.6% in those without distant metastases, 2-year--72%, and 3
year--47.6%. Our data point to new vistas in application of our techniques,
particularly, for short (up to 3 cm) inoperable esophageal cancers.
PMID- 17037044
TI - [Multiple endocrine neoplasia syndrome].
PMID- 17037045
TI - [Polyphasic evidence for the transfer of Promicromonospora yunnanensis to
Cellulosimicrobium cellulans].
AB - Polyphasic taxonomic investigations of Promicromonospora yunnanensis AS4.1333
deposited in the China General Microbiological Culture Collection Center (CGMCC)
indicated that strain AS4.1333 was closely related to Cellulosimicrobium
cellulans DSM43879(T), the two organisms shared a 16S rRNA gene similarity of
99.6% which correspond to 5 nt differences at 1423 positions. Corresponding DNA
DNA reassociation value was 89.3%, significantly higher than 70% cut-off point
recommended for the delineation of genomic species by Wayne et al. (1987).
Results of chemotaxonomic analyses of cell wall (Whole-organism hydrolysates were
rich in rhamnose, fucose and galactose; peptidoglycan type A4a), mycolic acids
(One dimensional TLC of whole-organism acid methanolysates revealed the absence
of a lower spot (Rf value around 0.47) that corresponded to mycolic acids),
principal menaquinones (MK-9 (H4)), phospholipid type (PV) and the G + C content
of the DNA (73.8 mol%) supported the conclusions of the genotypic analyses. The
very similar morphological and physiological characteristics agreed with the high
degree of relatedness. On the basis of phylogenetic analyses based on the almost
complete 16S rRNA gene sequence, DNA-DNA reassociation values, chemotaxonomic
properties, morphological and physiological characteristics, it is concluded that
strain AS4.1333 should be removed from the genus Promicromonospora, and strain
AS4.1333 and Cellulosimicrobium cellulans should be considered to be a single
species. Promicromonospora yunnanensis AS4.1333 was proposed to transfer into
Cellulosimicrobium cellulans. The type strain remains DSM43879T.
PMID- 17037046
TI - [Isolation and characterization of a new Pseudomonas strain against Phytophthora
capsici].
AB - One Pseudomonas strain GP72, which was against Phytophthora capsici, was isolated
from green pepper rhizosphere in Jiangsu province. It had distinctively
inhibitive effect on several kinds of pathogenic fungi; mostly of them are
soilborne pathogens. Therefore, this strain may be used for an effective
biocontrol strain in the crop protection. The morphological, biochemical and
physiological characteristics, Biolog GN, G + C mol% content and 16S rDNA
sequence analysis of this strain were studied. In comparison and conclusion of
all the experimental data, GP72 is identified as Pseudomonas chlororaphis. The
strain is single-cellular and motile by means of single polar flagellum. It was
not able to accumulate ploy-beta-hydroxybutyrate. Compared to P. aureofaciens 30
84, the strain was able to survive at the concentration of 5% NaCl. It could
strongly utilize 45 of 95 carbon-substrates; weakly utilize 6 of the whole carbon
substrates and never utilize 43 of the whole carbon-substrates resulting from
analysis of Biolog GN, bearing the similarity probability of 98% with Pseudomonas
chlororaphis and with the similarity index 0.72. The G + C content of the strain
DNA was 65.1 mol% using the thermal denaturation method. A phylogenetic tree was
constructed by comparing with the validly published 16S rDNA sequences of the
related type strains from GenBank, using the Neighbor-Joining method of Saitou
and Nei and the Clustal X program to do the multiple alignments. The tree
topology was tested by a bootstrap analysis of 1000 samplings. The overall
similarity value between strain GP72 and typical is the closest in the
phylogenetic tree. For the latest taxonomical development has put genus
Pseudomonas aureofaciens to the genus Pseudomonas chlororaphis, then it is
appropriate to say that GP72 belongs to the genus Pseudomonas chlororaphis. This
is the first time in China to report that a strain of Pseudomonas chlororaphis
was isolated from green pepper rhizosphere, having a strong inhibitive effect on
Phytophthora capsici and other soilborne pathogenic fungus. The other
characteristics and the biocontrol mechanism are yet to be further studied.
PMID- 17037047
TI - [Molecular identification and genetic diversity in Konnyaku's soft rot bacteria].
AB - The soft rot bacteria Erwinia are an important pathogens of konnyaku and other
ornamental plants. Thirty-three strains were isolated from soft-rotted konnyaku
and other ornamental plants. According to the characteristics of pathogenicity
and culture character on semi selective medium (crystal violet pectate, CVP),
most of strains tested caused rotten symptom in tubers and stems of konnyaku, and
characteristic deep cavities were formed on CVP. To amplify 16S-23S rDNA
intergenic transcribed spacer( ITS) by PCR and electrophorese through agarose
gel, most strains are clustered into two heterogeneous populations of Erwinia
carotovora subsp. carotovora, E.c.c. and Erwinia chrysanthemi, E. ch.. Besides,
several other strains could not be identified into species by ITS-PCR. The
characteristic band patterns of E.c.c. and E.ch. could be clearly distinguished
by repetitive element-polymerase chain reaction (rep-PCR,BOX and J3 primers). And
the fingerprinting of E.c.c. stains were also different from each other.
Dendrogram was generated from the data of primer BOX by using UPGMA analysis
because the primer BOX was higher resolution than other primers (such as prime
J3) for identifying the same intraspecies strains. Strains of E.c.c. were divided
into five groups on the 0.1 level of linkage distance.
PMID- 17037048
TI - [Construction of the shuttle expression-secretion vector with the promoters and
signal peptide-encoding sequence from Brevibacillus brevis].
AB - The multiple and tandem promoters and signal peptide-encoding sequence of cell
wall protein encoding gene was amplified from Brevibacillus brevis B15 total DNA,
the PCR fragment was cloned, sequenced and analyzed, then was submitted to
GenBank with a Accession No. AY956423. Another pair of primers were designed to
amplify the fragment again, BamHI and Pstl sites was introduced flanking the PCR
production. BamHI/Pstl digested fragment was cloned into the corresponding site
of shuttle vector pP43NMK to generate the expression-secretion vector pP15MK. The
inserted fragment was upstream of mpd gene and the signal peptide-encoding
sequence was fused in frame with the mpd gene, which its own signal peptide
encoding sequence was deleted. The recombinant vector was transformed into
Bacillus subtilis 1A751, under the control of the promoters and signal peptide
from Brevibacillus brevis B15, mpd gene was continuously expressed and secreted
at a high efficiency throughout the exponential growth phase and into the late
stationary phase, the expression production methyl parathion hydrolase (MPH) was
attached on the outside of the cell membrane. MPH activity accumulated to a
maximum level of 7.79 U/mL after 48 h of cultivation at the late stationary
phase, which was 8.1-fold higher than the expression level of the original
Plesiomonas strain M6.
PMID- 17037049
TI - [Analysis of mechanism and relationship of GacA and RsmA, two regulators of
antibiotics production in Pseudomonas sp. M18].
AB - In previous study, it has already been confirmed that the wild type strain of
Pseudomonas sp. M18 isolated from the agricultural soil can produce two
antifungal agents phenazine-1-carboxylic acid (PCA) and pyoluteorin (Plt).
Biosynthesis and secretion of these secondary metabolites contribute to its
biological control and suppression of soilborne pathogenic fungi. As main
regulators, GacA and RsmA differentially exert global regulation on production of
PCA and Plt, respectively. In order to study the regulatory mechanism of
secondary metabolites production in Pseudomonas sp. M18, a gacArsmA double
mutant, designated as M18GR, was constructed with insertional mutation. Then, the
mutant M18G, M18R, M18GR and the wild type strain M18 were inoculated into PPM or
King's medium B (KMB), respectively. During cultivation of strain M18 and its
derivatives, their PCA and Pit were respectively detected with High Performance
Liquid Chromatography (HPLC). The results showed that PCA production in the
mutant M18GR was lower than that in the mutant M18G and higher than that in the
mutant M18R. Plt production in the mutant M18GR was, however, much less than that
in the mutant M18R and much more than that in the strain M18 and the mutant M18G.
With these observations, it is tempting to suggest that biosynthesis of PCA and
Plt regulated by GacA or RsmA seem to occur at posttranscriptional level, not at
transcriptional level. This regulation on secondary metabolites seems to be
indirectly mediated by other unknown factors. Meanwhile, based on the
construction of two translational fusions, gacA'-'lacZ and rsmA'-'lacZ, the assay
of beta-galactosidase activities in KMB medium indicated that both GacA and RsmA
did not have autoinduction of their own gene expression, respectively. Although
GacA did not influence expression of the rsmA gene, RsmA could exert some
positive influence on the gacA gene expression in Pseudomonas sp. M18.
PMID- 17037050
TI - [Screen and identification of Streptocococcus pneumoniae genes specifically
induced in host].
AB - To identify in vivo-induced genes of S. pneumoniae and search new potential drug
targets and vaccine candidates, a selection system was developed based on the in
vivo expression technology (IVET). Promoter galU gene which is critical for the
capsular polysaccharide biosynthesis and lacZY gene which encodes bea
galactosidase were employed as dual reporter genes. The galU-deficient mutant of
S. pneumoniae is incapable of utilizing galactose and synthesizing capsular
polysaccharide, therefore can't survival in the host. Firstly, the random pieces
of S. pneumoniae chromosomal DNA (200-500 bp), obtained by partial Sau3Al
restriction digestion, were subcloned into the Bgl II site of pEVP3-galU.
Transformation by this plasmid library yielded promoter-trap library in S.
pneumoniae. Then, the library was used to infect animals. Bacteria were harvested
from lung tissue. White clones on TSA agar containing X-gal were used to reinfect
animals. The sequence of infection and sorting was performed twice, 165 white
clones harvested from the final round of infection were analyzed. A total of 15
unique sequences were obtained through in vivo screen. The bioinformatics
analysis showed that these ivi genes involved in colonization and adherence,
energy metabolism, nutrient substance transport, transcription regulation, DNA
metabolism and cell wall synthesis. And there were some hypothetical proteins
have unknown functions. Part of these genes may be related with virulence and can
be used as vaccine candidates and drug targets.
PMID- 17037051
TI - [Biological significance of amino acids deletion in NA stalk of H5N1 avian
influenza virus].
AB - It has been reported that NA gene of some H1N1 Influenza A virus strains isolated
since 1933 is characterized by a deletion of 11 to 16 amino acids in the stalk.
The spontaneous mutant in NA stalk of H1N1 virus lacks enzyme activity with large
substrate (fetuin) but not with small substrate (sialyllactose). Recently, H5N1
virus also has been found that NA has the same unique mutation in the stalk, a
deletion of 15 to 20 amino acids. However, biological significance of this
mutation has not yet been reported. In order to investigate biological
significance of the amino acids deletion in NA stalk of H5N1, five reassorted
H5N1/PR8 viruses were generated via eight-plasmid based reverse genetics system.
These five viruses were named 506, m506-, 646, m646+ and 196, respectively. The
six internal genes of recombinants were all from A/PR8/34(H1N1), and HA gene was
from A/G/JS/03(H5N1), however, they had different NA genes. 506 and m506- held NA
fragments derived from A/G/HD/00(H5N1), and the former was distinguished with a
longer NA which had no 20 amino acids deletion in the stalk. 646 and m646+ held
NA fragments from A/G/JS/03(H5N1), and the NA stalk of m646+ was 20 amino acids
longer than that of 646. The NA of 196 was derived from A/PR8/34 which had 15
amino acids deletion in its stalk. Biological characteristics of these viruses
showed that recombinants with different NA length could grow well in embryonated
SPF eggs, and their EID50, MDT, and viral titers were similar. However, the
length of NA was related to the capacity of eluting viruses from erythrocytes for
506 and 646+ which holding longer NA stalks eluted from erythrocytes more quickly
than m506-, 646 and 196 did. Moreover, 15 or 20 amino acids deletion in NA stalk
had a pronounced effect on virus growth ability in MDCK cells. Viral titers in
supernatant of MDCK infected with m506- or 646 were 10 to 100 folds higher than
those infected by 506 or m646+. And the plaque size of m506- and 646 were larger
than that of 506 and m646+. The results reveals that H5N1 AIV with amino acids
deletion in NA stalk would expand its host range. The unique amino acids deletion
in NA molecule of H5N1 may be associated with the adaptation of virus to
terrestrial poultry or the increasing ability of interspecies transmission.
PMID- 17037052
TI - [Rescue of a recombinant Newcastle disease virus expressing the green fluorescent
protein].
AB - A recombinant Newcastle disease virus (NDV) expressing the green fluorescent
protein (GFP) was generated by applying reverse genetics techniques. The GFP open
reading frame flanked by NDV transcription start and stop sequences was inserted
between the phosphoprotein (P) and matrix protein (M) in a full-length cDNA clone
of NDV Lasota vaccine strain. This plasmid transcribing antigenome RNA was
cotransfected with helper plasmids expressing viral nucleoprotein, phosphoprotein
and large protein into cells stably expressing T7 RNA polymerase. The rescued
virus was first propagated in 10-day-old embryonated eggs and the allantoic fluid
was used to infect primary chicken embryo fibroblasts (CEF) cells. The appearance
of GFP in live infected cells confirmed further the recovery of a recombinant NDV
(rNDV-GFP) expressing this reporter gene. Nine successive passages in embryonated
chicken eggs were performed. Allantoic fluid samples were then titrated by a
microtiter plate HA test. HA positive ailantoic fluid were used for further egg
passages. All the allantoic fluid samples were titrated by end point dilutions
and infected cells were examined for the presence of GFP expression. To analyze
virus growth, 10-day-old embryonated SPF chicken eggs were inoculated with 1 x
10(4) EID50 rNDV or rNDV-GFP. At 24,48,72 and 96 h p.i. the allantoic fluid of
inoculated eggs containing live embryos was harvested and clarified by
centrifugation. Supernatants were used for titration of EID50 in 10-day-old
embryonated SPF chicken eggs. rNDV and rNDV-GFP grew to similar titers (10(9)
EID50/mL). In order to test the virulence of rNDV-GFP, infectious allantoic fluid
of rNDV-GFP were inoculated into embryonated SPF chicken eggs at 1 x 10(6) EID50.
No dead embryonated egg was found within 96 hours. The replication kinetics and
pathogenicity in SPF embryonated eggs of rNDV-GFP did not differ significantly
from that of the parent virus. LaSota is a widely used NDV live vaccine strain.
The reverse genetic system established for this LaSota vaccine strain provided a
useful platform for development of novel live viral vector vaccines in future.
PMID- 17037053
TI - [Screening of microorganism producing polyunsaturated fatty acids with sugarcane
molasses].
AB - A strain name LB1 producing polyunsaturated fatty acids with sugarcane molasses
was screened form soil samples by the methods of Sudan Black B stain and the
determination of PUFAs' iodine value. Based on the grass morphological and
physiological characteristics and the sequence similarity of ribosomal DNA-ITS,
the strain was identified as Mucor recurvus sp.. The results of L64 (4(3))
orthogonal experiments indicated when Mucor recurvus was cultivated at 28 degrees
C for 5 days with 160 r/min, the yields of PUFAs with 10(0) BX sugarcane molasses
(pH 6.0) were up to 80.49% content of total fatty acids. The total lipids content
was 57.08% of fermentation biomass, which were composed of 15.42% Oleic acid,
14.38% Linolenic, 23.55% gamma-Linolenic, 3.06% alpha-Linolenic, 9.87%
Arachidonic acid, 8.14% Eicosapentaenoic acid, 6.07% Docosahexaenoic acid, etc.
PMID- 17037054
TI - [Identification of a strain NJ2 hydroxylating imidacloprid and the transformed
product].
AB - A strain named NJ2 was isolated from the soils in Nanjing area, and its resting
cells transformed IMI into a polar product. The strain was identified as
Stenotrophomonas maltophilia based on BioMerieux Vitek system and the analysis of
16S rDNA sequence. Mass spectrometry of the product extracted with an organic
solvent and re-crystallization gave m/z value of 272 for the molecular ion while
256 for substrate IMI. It demonstrated that the transformed product was the
hydroxylated derivate of IMI or hydroxy IMI. NMR analysis further indicated that
the hydroxyl moiety located at the ring of imidazolidine and the transformed
product was 5-hydroxy IMI. Kinetics of transformation IMI showed that the content
of IMI decreased 1.15 mmol/L and the content of transformed product 5-hydroxy IMI
increased 1.10 mmol/L after transformation for 10 days. The molar conversion
yield was 95.9%. The S. maltophilia NJ2 strain, with the characterization of
strong transformation ability and high molar conversion yield, can be used in
industrial production of 5-hydroxy IMI for synthesis of highly insecticidal
olefin IMI.
PMID- 17037055
TI - [Alleviative effects of nitric oxide on the biological damage of spirulina
platensis induced by enhanced ultraviolet-B].
AB - Continuing depletion of the stratospheric ozone layer by atmospheric pollutants,
in particular chlorofluorocarbons (CFCs), has resulted in an increasing incidence
of solar UV-B (280-320 nm) at the Earth's surface. Enhanced UV-B radiation has
been considered as important global environmental problem and results in
important effects to mankind and the entire global ecosystem. Nitric oxide (NO)
is not only a toxic molecule, one of reactive nitrogen species (RNS), but also an
important redox-active signaling molecule. NO is really a double-edged sword, it
can be either beneficial and activate defense responses in plants and animals or
toxic, together with ROS. Besides those, NO can also act as a signal molecule and
play very important roles in life of organisms. To study the effects of NO on the
biological specific property of enhanced UV-B stressed Spirulina platensis, the
chlorophyll-a, protein contents and biomass were investigated under enhanced UV-B
radiation and its combination with different chemical treatment. The changes of
chlorophyll-a, protein contents and biomass confirmed that 0.5 mmol/L sodium
nitroprusside (SNP), a donor of nitric oxide (NO), could markedly alleviate the
biological damage of cyanobacteria-Spirulina platensis 794 caused by enhanced
ultraviolet-B. Further results proved that NO significantly increase the content
of protein and proline. Meanwhile, the accumulation of reduced glutathione (GSH)
in S. platensis cells were raised under normal growth condition. But exogenous NO
could decrease the increasing of reduced glutathione (GSH) in enhanced UV-B
stressed S. platensis cells. These results suggest that NO has protective effect
and can strongly alleviate biological damage caused by UV-B stress in S.
platensis 794 cells. For the first time, reported the effect of NO on the
regulating ability of biological damage of S. platensis induced by enhanced UV-B.
Therefore, further investigations will be necessary to inquire into the
interaction and inter-correlation of signal molecules and the mechanism in
cyanobacterium under enhanced UV-B stress.
PMID- 17037056
TI - [Cloning, expression and purification of D-carbamoylase from Sinorhizobium
morelens S-5].
AB - A N-carbamoyl-D-amino acid amidohydrolase gene (hyuC) from Sinorhizobium morelens
S-5 was cloned by LA PCR, and its nucleotide sequence was determined. The deduced
amino acid sequence encoded by the hyuC gene exhibited high homology to the amino
acid sequences of D-carbamoylase from other sources. The gene could be highly
expressed in Escherichia coli, and the recombinant enzyme was purified 16.1-fold
to homogeneity with a yield of 21.2% by heat treatment and three steps of column
chromatography. The results of gel filtration on Superdex 200 HR and SDS
polyacrylamide gel electrophoresis suggested that the enzyme was a tetramer
protein of identical 38-kDa subunits. The recombinant enzyme catalyzed the
hydrolysis of N-carbamoyl alpha-amino acid to the corresponding free amino acid,
and it was strictly D-specific. The enzyme showed broad substrate specificity,
and exhibited high activity in the hydrolysis of N-carbamoyl-D-p
hydroxyphenylglycine as substrate. The enzyme did not hydrolyze N-carbamoyl-beta
alanine. The optimum pH and temperature of the enzyme were pH 7.0 and 60 degrees
C, respectively. Enzyme activity was slightly improved by Ca2+ and Fe2+, and
nearly not affected by metal chelators and sulfhydryl reagents. The enzyme showed
high thermal and oxidative stability. These results show that the enzyme has
great potential for industrial application.
PMID- 17037057
TI - [Study on the screening of lactamase and its fermentation conditions].
AB - (-)-gamma-Lactam is one of the key starting materials for the synthesis (-)
cabovir and (-)-abacavir, which serve as two powerful antiviral agents. The
production of gamma-lactam using enzymatic resolution of racemic gamma-lactam was
attempted in the paper. 20 out of 69 strains capable of producing lactamase were
screened from soil samples collected in several districts throughout Beijing;
particularly N-actylphenylalanine was used as sole carbon source in the screening
method. It was found by chiral HPLC analysis that strain L29-9 was able to
enantioselectively hydrolyze the (+)-isomer in the racemic lactam, thus giving
the desired (-)-gamma-lactam with high enantiomeric excess (> 70%). Ferment
conditions of strain L29-9, including carbon source, nitrogen source, pH, and
culturing time, were studied and the optimum conditions were as follows: citric
acid 2 g/L, yeast extract 5 g/L, pH 7.0, culturing for 40h. Biotransformation
using whole cells of the strain was inducted at 30 degrees C for 12h, giving (-)
gamma-lactam as enantiopure product with yield up to 40% and 99.5% e.e.
PMID- 17037058
TI - [Cloning of the gene encoding a thermostable alpha-amylase from bacillus
licheniformis CICIM B0204 and functional identification of its promoter].
AB - Thermostable alpha-amylase, catalyzing the hydrolyzation of starch to dextrin,
maltose and glucose at higher temperature, is one of the most industrial
important enzymes. Several species of Bacillus have been found and genetic
improved to produce the thermostable alpha-amylases. In present study, a gene,
amyL, coding for a thermostable alpha-amylase with its flanking sequences was
cloned from an industrial Bacillus licheniformis CICIM B0204 by using a
combination of routine polymerase chain reactions (PCR) and inverse PCR with a
pair of initial primers derived from the highly conserved region of bacterial
alpha-amylase genes and the functional identifications of the cloned amyL and the
activities of its promoter and signal peptide in Escherichia coli were
investigated. The amyL was composed of 1539 bp with 180 bp at upstream for its
promoter and 160 bp at downstream for its terminator. The deduced mature peptide
of the a-amylase was composed of 512 amino acid residues and its signal peptide
29 amino acid residues at N-terminal. The nucleotide and deduced amino acid
sequences of amyL were extremely similarity to those from Bacillus species with
three amino acid residues difference (Arg163-->Leu, Ser339-->Gly, Ala349-->Ser)
comparison to that from a laboratory strain B. licheniformis 584. Under the
control of T7 promoter, the structural region of amyL was functionally expressed
in Escherichia coli. Additionally, the structural region of the gene coding for a
beta-mannosidase from B. licheniformis CICIM B2004 was inframely inserted into
the downstream of the promoter and signal sequence of amyL and expressed in E.
coli. The amyL promoter and signal sequence was functionally directed the
expression and secretion of the beta-mannosidase in E. coli cells with the
expression level of 295 U/mL.
PMID- 17037059
TI - [Cloning and expression of lumbrokinase gene in Pichia pastoris].
AB - Lumbrokinase gene F238 was amplified by RT-PCR from the total RNA of earthworm
(Eisenia fetida). The gene including signal peptide sequence was inserted into
pUCm-T vector to construct pUCm-T-F238. The product was sequenced. The GenBank
accession number was DQ202401. Lumbrokinase F238 comprised 738bp and included an
open reading frame that encoded a polypeptide of 245 amino acid residues,
containing a signal peptide of 7 amino acid residues and a mature peptide of 238
amino acid residues. Both nucleotide and amino acid sequences homologies were 99%
after the sequence was compared with Lumbricus rubellus F-III-2. There were two
base pair mutations, which subsequently caused two amino acid mutations. The
characteristics and structure of F238 was analysed and predicted with biology
softwares and databases. The pl of F238 was 4.61. It had eleven Cysteines, which
formed three disulfide bonds. Its secondary structure mainly consisted of beta
sheet. Lumbrokinase F238 had serine active center. It was a protease in trypsin
family of serine protease superfamily. Lumbrokinase gene F238-m without signal
peptide sequence was obtained by PCR using pUCm-T-F238 as template. The
expression vector pPIC9-F238-m was constructed by inserting gene F238-m into
yeast expression and secretion plasmid pPIC9. Plasmid pPIC9-F238-m was linearized
with BgIII and then transformed into Pichia pastoris strain GS115 cell by
electroporation method. Phenotypes of transformants were screened in MM and MD
plates to ensure the integration of lumbrokinase gene F238-m into yeast
chromosome DNA. Methanol was added to a final concentration of 0.5% for the
expression of recombination protein every 24h to maintain induction. The result
of SDS-PAGE showed that the molecular weight of the expression product was about
28 kDa, in correspondence with the theoretical molecular weight. After the
induction of expression, the fibrinolytic activity of the supernatant was
measured using artificial fibrin plates. Then the engineering strain of high
activity was obtained, and the fibrinolytic activity was up to 100 U/mL.
PMID- 17037060
TI - [Screening of a low alcohol dehydrogenase activity mutant of rhizopus oryzae and
the regulation of Zn2+ and Mg2+].
AB - Ethanol is the main by-product in the fermentation broth of Rhizopus oryzae
As3.3461 for the production of high-optical purity L-lactic acid. Alcohol
Dehydrogenase (ADH) is the branch pathway enzyme that catalyzes the
transformation of ethanol from pyruvate in Rhizopus oryzae, which decreases the
conversion rate of glucose to L-lactic acid. Thus, screening the mutants with
lower ADH activity may increase lactate production dramatically. In present
study, Rhizopus oryzae As3.3461 was mutated with N-methyl-N'-nitro-N
nitrosoguanidine (NTG), and 21 mutants which showed lower ADH activity were
isolated with selective medium of Yeast-Peptone-Dextrose (YPD) containing 0.6%
allyl alcohol (V/V). Compared with other mutants, the 12th mutant strain (named
as HBF-12) shows the highest conversion rate of L-lactic acid. By contrast with
Rhizopus oryzae As3.3461, the parent strain, the ethanol production and the ADH
activity of HBF-12 decrease 73.6% and 76%, respectively. Whereas, the L-lactic
acid production and the LDH activity of HBF-12 increase 41.2% and 19.6% than
those of the parent strain, respectively. The activities of ADH and LDH of HBF-12
were regulated by Zn2+ and Mg2+, but showed opposite effects. Added with Zn2+ to
the concentration of 0.01% improves the ADH activity dramatically, but inhibits
the activity of LDH. By contraries, added with Mg2+ improves the LDH activity
markedly, but inhibits the ADH activity slightly. In fermentation experiment, the
addition of Zn2+ and Mg2+ show different effects on the accumulation of ethanol,
L-lactic acid and the biomass in mutant HBF-12. When improve the concentration of
Zn2+, the accumulation of L-lactic acid and the biomass show the decreased trend,
but the production of ethanol show positive effect. With the improvement of the
concentration of Mg2+, the production of lactic acid and biomass increase
markedly, but no effect on the production of ethanol. When ferment under the
concentrations of Zn2+ 0.01% and Mg2+ 0.04% in fermentation medium, the lactate
production of HBF-12 reached the highest level, 96.21 g/L.
PMID- 17037061
TI - [The effects of the humic substances on Azoreduction by Shewanella spp].
AB - Under anaerobic conditions, Shewanella cinicaD14(T), Shewanella baltica and
Shewane-lla putrefaciens are capable of high-rate azoreduction and humus
reduction. The results indicated that at low concentration ( <2 mmol/L) AQS was a
accelerator for bacterial azoreduction. However, when the concentration of AQS
was more than 5 mmol/L a strong inhibition was occurred. On the other hand, the
concentration of AQDS as high as 12 mmol/L the inhibition of azoreduction was
still not exhibited, but the effect of acceleration was gradually decreased with
the concentration of AQDS increasing (1 mmol/L to 12 mmol/L). 6 azo dyes (Table
1) were tested, all of which had a similar results. These results indicated that
the humic substances were not only as a redox mediator during the azoreduction,
but also as the competitor for electron from respiration chain. Because the humic
substances could be act as the terminal electron acceptor for bacterial anaerobic
respiration. AQS and AQDS exhibiting different behaviour on the azoreduction were
determined by their standard redox potentials.
PMID- 17037062
TI - [Diversity of actinomycetes associated with root-knot nematode and their
potential for nematode control].
AB - Twenty actinomycetes were isolated from root-knot nematode eggs and females
collected from 11 plant root samples infested by Meloidogyne spp.. The isolates
were assigned to the genera Streptomyces, Nocardia and Pseudonocardia
respectively, based on analysis of morphological characteristics, cell-wall DAPs
and 16S rRNA gene sequences. 80% of them were streptomycetes. Biocontrol
potential of the isolates against Meloidogyne hapla was evaluated in liquid
culture in vitro. The average percentages of egg parasitism, egg hatching, and
juvenile mortality were 54.1, 40.4 and 26.2, respectively. Three Streptomyces
strains and one Nocardia strain with high pathogenicity in vitro were selected to
determine their ability to reduce tomato root galls in greenhouse. The results
demonstrated good biocontrol efficacy (31.4%-56.4%) of the strains.
PMID- 17037063
TI - [Comparative susceptibility of Myzus persicae to 16 strains of Metarhizium spp.
from different host insects and geographic regions].
AB - The fungal biocontrol agents Metarhizium species and varieties have been widely
applied for insect control but their targets rarely aim at sucking-type
homopteran insects such as aphids. To search for fungal candidates against
aphids, 16 strains of four varieties of two Metarhizium species, most of which
originally infected foliage insect pests in Asia, Africa and America, were
bioassayed to compare their virulence to Myzus persicae apterae. With each
strain, each of three conidial suspensions was sprayed onto aphids in three Petri
dishes (about 40 aphids per dish) in a Potter Spray Tower, resulting in deposits
of conidia for low, medium and high dosage treatments (no. conidia/mm2). After
spray, all aphids were reared at the regime of 25 +/- 1 degree C and 12:12 L:D
and observed daily for counts of mycosed cadavers. As a result, 10 strains of M.
anisopliae (Ma) and M. anisopliae var. anisopliae (Maa) caused 67%-100%
mortalities at the high dosage of about 1000 conidia/mm2 within 7 days after
spray whereas other strains, including M. anisopliae var. majus, M. anisopliae
var. acridum, M. flavoviride var. minus, killed a very small number of aphids
even at the high conidial dosage. Of the 10 strains, Ma 456 and Maa 3332 were
highly virulent to the aphid species based the modeling of their time-dose
mortality data. The LC50 of the two strains were estimated as 113 and 260
conidia/mm2 on day 4, 32 and 43 conidia/mm2 on day 5, 17 and 26 conidia/mm2 on
day 6, and only 11.4 and 19.9 conidia/mm2 on day 7, respectively. Thus, both
strains are highly potential for use in microbial control of aphids.
PMID- 17037064
TI - [Relationships between phosphine content of samples and their microbial
populations and enzyme activities].
AB - The relationships between phosphine content and various microbial florae,
activities of different enzymes were investigated. The results indicated that the
phosphine content of samples from various environments was positively related to
total anaerobic microorganisms, organic phosphate compounds-dissolving bacteria,
denitrifying bacteria, alkaline phosphatase activity and dehydrogenase activity
of the samples. The correlation coefficients (R2) for these were 0.93, 0.90,
0.69, 0.79 and 0.82, respectively. The results also showed that the phosphine
content was not related to total aerobic microorganisms, inorganic phosphate
compounds-dissolving bacteria, sulfate-reducing bacteria, acidic phosphatase
activity. In addition to formerly results, the results might infer that the
formation of phosphine was due to the reduction of organic phosphate compounds by
anaerobic heterotrophic microbes, especially the denitrifying bacteria by using
reducing sugar.
PMID- 17037065
TI - [Construction of double-labelled carbofuran-degrading bacterium Sphingomonas sp.
CDS-1].
AB - The genomic DNA of a carbofuran-degrading bacterium Sphingomonas sp. CDS-1 was
digested by Sau3Al and ligated to pRobe-GFP digested by BamHI, and the product
was transformed to the E. coli DH5alpha competent cells. Fifty positive clones
that could emit green fluorescence under UV were selected from about 1 x 10(4)
clones grown on selective plates AmpLB. One clone F7 with the strongest
fluorescence was selected, the recombinant plasmid pF7 from this clone was
digested with EcoR I & Hind III and the DNA fragment comprising gfp and promoter
of Sphingomonas sp. CDS-1 was recovered, which was subsequently cloned into the
broad host vector pPZP201 to construct a new plasmid pPZP201-gfp. pPZP201-gfp was
introduced into Sphingomonas sp. strain CDS-1 by triparental conjugation to make
strain CDS-gfp. gfp was expressed strongly and stably in strain CDS-gfp after 10
times successive re-culturing (48 h/time). The linA gene was inserted into Not I
cut transposon vector pUT/mini-Tn5 to construct a new transposon vector pUT/mini
Tn5-linA. With the aid of helper plasmid pRK600, pUT/mini-Tn5-linA was introduced
into CDS-gfp, the dehydrochlorinase gene linA was integrated into the chromosome
of CDS-gfp by transposing. The double labelled strain CDS-GFP-LinA was
constructed. This strain was also a genetic engineering strain that was able to
degrade gamma-hexachlorocyclohexane and carbofuran simultaneously. All of these
results laid a foundation for the study of ecological performance of Sphingomonas
sp. CDS-1.
PMID- 17037066
TI - [Community composition and dynamics of airborne bacteria in Beijing].
AB - Airborne bacteria are important biological components of the aerosol. They have a
close relation with human health. The much higher concentrations can result in
kinds of microbial disease. Using BIOLOG identification technology, the study on
the community structure and dynamics of airborne bacteria was carried out in
three typical functional areas in Beijing by systemic site sampling. Results show
that the gram positive bacteria contributing 80%-85% were much more than the gram
negative bacteria. Amongst 47 genera of bacteria including 31 Gram positive
bacteria and 16 Gram negative bacteria, Micrococcus, Staphylococcus, Bacillus,
Corynebacterium, and Pseudomonas were dominant, and Micrococcus contributing 20%
30% was the most dominant genus. The concentration of airborne bacteria was
significant lower in GGR than in CER and MTL. In a year, the bacterial
concentrations of summer and autumn were much more than those of winter and
spring in CER and MTL, and there were no significant variations of bacterial
concentrations in GGR. In different periods, the lower concentration of airborne
bacteria was exhibited at 13:00.
PMID- 17037067
TI - [Expression of alpha-toxin gene of Clostridium perfringens type A and its primary
immunological protective function].
AB - Alpha-toxin gene was amplified from chromosomal DNA of Clostridium perfringens
type A by polymerase chain reaction (PCR). PCR product was inserted into vector
pGEM-T directly. The cloned recombinant plasmid pXCPA02 possesses positive
nucleotide sequence of alpha-toxin. A 1.2 kb alpha-toxin gene fragment was
cleaved with restriction endonucleases Nco I /EcoR I from plasmid pXCPA02, and
then inserted into an expression vector pET-28c which cleaved with Nco I /EcoR I
by blunt-end ligation. The recombinant expression plasmid pXETA02 was studied in
detail by restriction endonucleases analysis and nucleotide sequencing. The
results showed that the recombinant expression pXETA02 possessed a positive alpha
toxin gene sequence and reading frame. BL21 (DE3) (pXETA02) could produce alpha
toxin and the expressed products were recognized by alpha-toxin monoclonal
antibodies with ELISA and Western blot. The expression optimization result
indicated that the alpha toxin gene expression optimized condition with IPTG
induction is culture medium pH 7.5, culture temperature 37 degrees C, joining
IPTG to final concentration 0.8 mmol/L when the recombinant strain growth density
OD600 achieved 0.8, and induction time 5h. The expression level of the alpha
toxin proteins were about 34.28% of total cellular protein with IPTG induction by
SDS-PAGE and thin-layer gel scanning analysis. The alpha toxin gene expression
optimized condition with lactose induction is culture medium pH 7.5, culture
temperature 37 degrees C, joining lactose to final concentration 0.1 g/L when the
recombinant strain growth density OD600 achieved 0.8, and induction time 5h. The
expression level of the alpha-toxin proteins were about 23.82% of total cellular
protein with lactose induction by SDS-PAGE and thin-layer gel scanning analysis.
More importantly, Immunization in a mouse model with crude preparation containing
the alpha-toxin protein inclusion bodies or inactivated recombinant strain
induced protection against at least 1 MLD of the toxin from Clostridium
perfringens type A.
PMID- 17037068
TI - [Comparative proteomics research on THP-1 cells infected with Brucella].
AB - Brucella is a facultative intracellular pathogen that survives and multiplies
inside host macrophages to cause brucellosis. The response of macrophage plays an
essential role in the initiation of immune process following Brucella challenge.
Nowadays, proteome approaches have been widely used in many different systems to
investigate host-microbe interactions. The effect of pathogen-specific virulence
mechanism can now be dissected using bacterial mutants and comparing different
species. Attenuated vaccine strain 104M is defective in multification in host
macrophage and is cleared relatively rapidly from tissues of the host, whereas
virulent strains Brucella abortus 544A can produce chronic infection and cause
brucellosis. In order to understand the underlying mechanisms of virulent
Brucella intracellular survival, and detect the different-expressed proteins of
THP-1 cells after infection with attenuated and virulent strains of Brucella
abortus, a comparative proteomics research was conducted. Whole cellular protein
profiling of THP-1 cells was presented by two dimensional (2D) electrophoresis
and Coomassie Blue staining. After in-gel protein digestion, the different
expressed spots were detected by matrix assisted laser desorption ionization-time
of flight mass spectrometry (MALDI-TOF-MS). All the peptide mass fingerprints
(PMFs) were searched by the program Mascot developed by Matrix Science Ltd. For
identifying proteins, database of hemo sapiens was used. A total of 38 proteins
with changed expression level were found. These proteins can be grouped into two
familes: (1) the expression level increased after infection with 544A; (2) the
expression level increased after infection with 104M. Out of the 38 proteins, 10
were mainly in the field of signal transduction, 6 were cytoskeletal proteins, 8
were substance metabolism related proteins and 3 were cell stress and defense
associated proteins. Functions of the remaining proteins were unknown. These
results provide insight into the changed global protein patterns of THP-1 cells
after infection as well as a comprehensive foundation to further study of host
bacterial interaction.
PMID- 17037069
TI - [Isolation and identification of Streptococcus suis serotype 2 from sick-pig
samples of Sichuan province].
AB - Streptococcus suis serotype 2 (SS2) is a major pathogen frequently associated
with infections in pigs. There are presently 35 serotypes of S.suis (serotype 1
to 34 and serotype 1/2) recognized on the basis of capsular antigens. Few people
were reported to infect with SS2 in the past years. However, an accidental case
happened in Sichuan province of China in 2005. Some people got ill and died, and
all of them were closely contacted with sick pigs. Based on clinical features and
epidemiologic data, this case could be caused by SS2 infection. Liver, spleen,
kidney, lung and serum samples were collected and used for pathogen isolation and
identification in laboratory, three strain bacteria were isolated. The three
strains of SS2 showed typical morphology of SS2 on blood agar and under
microscope with Gram stain. They were also agglutinated with standard serum of
SS2. Biochemical characteristics of the three bacteria were tested using API 20
strep and analyzed by API software (version 3.3), results showed they were SS2.
Four pairs of primer were designed, which were exactly matched the extracellular
factor gene, muraminidase released protein gene, capsular polysaccharides gene
and 16S rRNA gene respectively. These primers were used on polymerase chain
reaction (PCR), and the PCR products were 626bp, 885bp, 487bp and 297bp on
agarose gel, respectively. Drug sensitivity test were also done and results
showed that they were sensitive to cefazolin, clindamycin, erythromycin,
levofloxacin, nitrofurantoin, penicillin-G, and vancomycin and resistive to
tetracycline. Balb/c mice infected with the isolated SS2 strain showed swelling
in stomach and intestine, cyanochroia at mouth and suggillation under skin, which
were similar to the clinical features of patients. Streptococcus suis serotype 2
were also found on lung sheeting sample under microscope with Gram stain. Rabbits
infected with the isolated SS2 showed the similar clinical features with mice.
PMID- 17037070
TI - [Co-expressed GP5 and M proteins of porcine reproductive and respiratory syndrome
virus can form heterodimers].
AB - In order to investigate the characterization of in vitro co-expressed GP5 and M
proteins of porcine reproductive and respiratory syndrome virus (PRRSV),
eukaryotic expression plasmids pCI-ORF5 (expressing GP5 protein alone), pCI-ORF6
(expressing M protein alone), and pCI-ORF5/ORF6 (co-expressing GP5 and M
proteins) were constructed. After transient transfection, Western blot analysis
under nonreducing condition demonstrated that co-expressed GP5 and M proteins
could form disulfide-linked heterodimers (GP5-M) in transiently transfected BHK
21 cells. To further study the influence of GP5-M heterodimers formation on the
subcellular localizations of GP5 or M proteins, green fluorescence protein (EGFP)
and red fluorescence protein (RFP) were used as markers. The results of
fluorescence distribution showed that co-expressed GP5-EGFP chimera and M-RFP
chimera boosted the transport of GP5 from the endoplasmic reticulum (ER) to the
Golgi complex, indicating that the formation of GP5-M heterodimers may be
involved in posttranslational modification, transport, and subcellular
localization of GP5. These results presented here lay foundation to further study
the molecular mechanism of GP5-M heterodimer formation and its role in protective
immunity of PRRSV.
PMID- 17037071
TI - [Generation of recombinant vaccinia virus expressing attachment glycoprotein of
Nipah virus].
AB - The mammalian condon optimized G gene was synthesized by over-lapping PCR and
used to generate recombinant vaccinia virus, rWR-NiV-G. The expression of Nipah
virus G protein in rWR-NiV-G infected HeLa cells was confirmed by western-blot
with NiV G protein specific mouse antiserum generated by DNA immunization.The
recombinant G protein showed sensitive and specific antigenic reaction to rabbit
serum anti-Nipah virus in indirect florescence. Syncytium formation was induced
in BHK cells by rWR-NiV-G infection following NiV F protein expressing plasmid
pCAGG-NiV-F transfection. Immunization with rWR-NiV-G elicited G protein specific
antibody responses in mice. The prokaryotic expressing G protein fragment showed
sensitive and specific antigenic reaction to NiV G protein specific antibody from
rWR-NiV-G immunized mice serum in indirect ELISA. Furthermore, the G protein
specific antibodies could neutralize the infectivity of the recombinant Vesicular
Stomatitis Virus pseudotype VSVAG * F/G, in which the VSV envelope protein G gene
was replaced with the green fluorescent protein gene (VSVAG * G, Whitt MA) and
complemented with Nipah virus F and G glycoprotein expressed in transient (VSVAG
* F/G).The results here demonstrated the G protein expressed by rWR-NiV-G keeps
native immunogenicity and biological activity. The recombinant virus could be
promising vaccine strategy for the prevention of Nipah virus.
PMID- 17037073
TI - [Primary study on acid tolerance mechanism of a wild aciduric Rhizobium strain
isolated from Pueraria lobata].
AB - An aciduric Rhizobium strain, named as PR389, was isolated from the nodule of
wild Pueraria lobata which grew in yellow soil (pH 4.6) on the Jin-yun Mountain
in Bei-bei, Chong-qing city. The isolated strain, which could grow under pH 4.6
distinct from the optimal pH 6.5-7.5 for rhizobium, showed some typical features
of aciduric rhizobium. This was also confirmed by the proton flux assay. Compared
to the acid-sensitive Rhizobium strain PR21, the cell membrane of PR389 could
hold back excessive H entering cell. This feature can protect PR389 from harm of
acid. In the test of acid tolerance, the aciduric ability of strain PR389 under
low acidic (pH 3.8) was restrained by antibiotic chloramphenicol. It was
speculated that special proteins in the cells of PR389 could be induced and
synthesized in acidic environment.
PMID- 17037072
TI - [Isolation, identification and phylogenetic analysis of a pathogenic bacterium in
channel catfish].
AB - A pathogenic bacterium (CCF00024) was isolated from the kidney and liver of the
diseased channel catfish with acute epidemic disease. Artificial infection proved
that the bacterium was the pathogen of the disease. Its morphological,
physiological, biochemical characteristics and 16S rDNA sequence analysis were
studied. The isolated strain is an aerobic, non-fermentative bacterium. The
bacteria are gram negative, rods, with polar multi-flagella; Oxidase-negative,
methyl-red-negative, lysine decarboxylase-positive, DNAase-positive, urease
positive, lipase-positive and protease-positive. The bacteria can't utilize most
of sugars with production of acid, except maltose and mannose. A phylogenetic
tree was constructed by comparing the 16S rDNA sequence of the isolated strain
(GenBank accession number AY970826) with other relative bacteria species in the
RDP and GenBank databases. In the phylogenetic tree CCF00024, Stenotrophomonas
maltophilia 13637T, Stenotrophomonas maltophilia MG958T, and Stenotrophomonas
maltophilia M5-1 constitute a branch. The similarity value between strain
CCF00024 and those 5 strains Stenotrophomonas maltophilia are 99.4%-99.6%.
According to morphological, physiological, biochemical characteristics and
phylogenetic analysis, the isolated strain (CCF00024) is identified as
Stenotrophomonas maltophilia.
PMID- 17037074
TI - [Construction of an engineering strain producing alkaline pectate lyase with
pHSh].
AB - The structure gene PL from Bacillus subtilis WSHB04-02 encoding pectate lyase was
amplified by PCR. The pET22b(+) vector, with leader sequence PelB, harboring PL
gene was constructed. From pET22b(+) PL, the fragment of PL and leader sequence
PelB was amplified by PCR together, which was transformed into E. coli JMI109.
The expression of PL in E. coli JM109 was not evidently different from E. coli
BL21DE3 (pET22b(+) PL) which promoter is T7. SDS-PAGE analysis showed that the
molecular weight of expressed recombinant PL was about 43 kDa which was the same
as calculated value. The results indicated the expression of pHsh PL in E. coli
JM109, Hsh as a promoter, was satisfied and low-cost. It is significant for large
scale fermentation of pectate lyase.
PMID- 17037075
TI - [Sequence analysis of integration sites of reticuloendotheliosis virus LTR in
fowlpox vaccine virus genomes].
AB - By use of genomic DNA prepared from 5 fowlpox virus (FPV) vaccines made in China
(from Shandong, Beijing, Liaoning, Zhejing and Shanghai respectively) as the
templates, reticuloendotheliosis virus (REV) LTR was amplified in PCR with a pair
of primers synthesized according to the sequences flanking the integrated REV
5'LTR in FPV genomes published in US and Australia. Sequence analysis indicated
that the REV-5'LTR integration sites in genomes of all 5 Chinese PFV vaccine
products were identical to American and Australian FPV vaccines with integrated
REV-5' LTR. Among the 5 FPV vaccine products made in China, 3 productes Vac-B-Ch,
Vac-D-Ch and Vac-E-Ch had the integrated REV-5' LTR sequences of 223bp with 100%
homology to that in American vaccine Vac-3-Am and Australian vaccine Vac-M3-Au.
The integrated 505bp REV-LTR sequences in another Chinese products Vac-A-Ch and
Vac-C-Ch had 99.6% homology to the integrated REV-LTR of American vaccine Vac-1
Am and Australian vaccine Vac-S-Au. However, REV-5'LTR integrated in all 5 FPV
vaccines made in China gave only 75.4%-91.5% homology to LTR of a Chinese field
strain HA9901 of REV. Based on the above results, it is reasonable to speculate
that the virus stocks for the 5 Chinese FPV vaccine products were rather
originally imported with their integrated REV LTR than recombinated with LTR of
REV local field strains in China.
PMID- 17037076
TI - [Arginine metabolism in wine malolactic bacteria].
AB - Arginine metabolism in wine malolactic bacteria may increase the concentration of
ethyl carbamate (EC, a known carcinogen with the potential toxicological effects)
in wine, which makes a profound impact on wine hygienic quality. In fact, recent
advanced studies have proved that arginine metabolism in wine malolactic bacteria
is via arginine deiminase pathway (ADI pathway), and this pathway is composed of
three enzymes: arginine deiminase (ADI), ornithine transcarbamylase (OTC),
carbamate kinase (CK). The possible mechanisms of arginine transport and the
regulation of major enzymes for arginine metabolism as well as the mechanism of
ADI pathway and its molecular characteristics are reviewed. The study on arginine
metabolism in wine malolactic bacteria has practical and theoretical significance
for the safety and high quality of wine.
PMID- 17037077
TI - [A novel application of baculovirus in mammalian gene therapy].
AB - Baculovirus has been widely used for the production of recombinant proteins in
insect cells. The extremely high yield by baculovirus-infected insect cells or
larvae makes it an attractive tool for pharmaceutical protein production. Since
the finding that baculovirus can efficiently transduce mammalian cells, the
applications of baculovirus have been greatly expanded. Although AcMNPV
(Autographa californica multiple NPV) fails to replicate in vertebrate cells, it
does express alien genes with levels of expression that are dependent on the
strength of the promoter used to drive transcription of the foreign gene.
Following these findings, subsequent studies have rapidly expanded the list of
permissive cells that include cell lines originating from human, rodent, porcine,
bovine and even fish sources. Many tries have been done to study the mechanism of
baxulovirus entry into mammalian cells, but the events responsible for virus
uptake and detailed mechanisms of intracellular movement and nuclear entry of the
virus are still largely unknown. The application of modified baculoviruses for in
vivo gene delivery has also been demonstrated. In contrast to other commonly used
viral vectors, baculoviruses have the unique property of being incapable of
initiating a replication cycle and producing infectious virus in mammalian cells.
The AcMNPV genome is large, thus rendering the virus flexibility to carry
multiple genes or large inserts. The recombinant viruses can be readily
constructed and produced to high titers simply by infecting insect cells,
initiate little to none microscopically observable cytopathic effects on
mammalian cells and have a good biosafety profile. These attributes will
undoubtedly lead to the increased application and continued development of this
system for efficient gene delivery into mammalian cells.
PMID- 17037078
TI - [Progress on engineered strains for ethanol production].
AB - With the 21 century's coming, the era of cheap oil is coming to the end. There
has been an increasing worldwide interest in fuel ethanol. In the last two
decades, lots of work has been done to develop strains for ethanol producing.
Research progress on metabolic engineering of strains for fuel ethanol production
is summarized, including genetically engineered Saccharomyces cerevisiae to
utilize starch, pentose and cellulose, Zymomonas mobilis to ferment arabinose and
xylose, Escherichia coli and Klebsiella oxytoca to introduce heterogenous ethanol
production pathway. The aim of engineering these strains is to obtain an ideal
microorganism which can converse the available carbon sources to ethanol rapidly
and efficiently with high tolerance to ethanol and to inhibitory components in
the cheap materials such as lignocellulose hydrolysate. The importance of fuel
ethanol will be a stimulus to develop engineered hardy strains to utilize cheap
materials for high ethanol concentration production. Since both Saccharomyces
cerevisiae and Zymomonas mobilis are generally regarded as safe (GRAS),
genetically engineered Saccharomyces cerevisiae which can utilize raw starch
directly and recombinant Zymomonas mobilis which can ferment glucose, arabinose
and xylose in the lignocellulose hydrolysate have potential application to
industry in the near future.
PMID- 17037079
TI - [Progress and investigation of neuronal plasticity interfered by Borna disease
virus infection].
AB - Borna disease virus (BDV) is highly neuronotropic. Recently, more and more
investigations indicated that BDV infection was close related to human
neuropsychic disorders. However, the mechanism underlying the disorders was
unclear to date. Some investigators thought neuronal plasticity changes by BDV
infection in the central nervous system may be it's cardinal basis. Many
researchers have studied the molecular mechanisms, which might lead to
disturbances in neuronal plasticity by BDV infection, through infection-based
animal modes such as gerbils modes, rats modes, mice modes and transgenic mice
modes. The results showed that neuronal plasticity was interfered by BDV
infection through interference with trophic support from astrocytes to neurons,
interference with amphoterin signaling and interference with neurotrophin
signaling. The disturbances in neuronal plasticity would result in cerebral
disorders and cause behavior alterations and psychic alterations of host. In the
following years, the ability to manipulate the BDV genome may help uncover
unrecognized aspects of the basic mechanisms operating in the regulation of
neuronal plasticity of interference with neuronal physiology caused by BDV, give
academic foundation for clinical prevention and therapy of BD.
PMID- 17037080
TI - [Progress on lactococcus lactis expressing heterologous antigens as live mucosal
vaccines].
AB - Lactic acid bacteria (LAB) are natural commensals of the gastro-intestinal tracts
of humans and most animals. They are considered to be safe bacteria with a GRAS
(generally regarded as safe) status. The studies on LAB as live vehicles for
expression of heterologous proteins or antigens have gained great progress in the
past decades. Lactococcus lactis, an important species of LAB, possesses many
properties that make it an ideal candidate for expressing and delivering
heterologous proteins. With the significant advances in the genetic study of LAB,
a series of constitutive or inducible gene expression systems as well as protein
targeting systems had developed in Lactococcus lactis. Several antigens of
pathogenic microorganisms, such as C subunit of tetanus toxin (TTFC) and the
Brucella abortus ribosomal protein L7/L12, were successfully expressed in
Lactococcus lactis. And it was showed that the recombinant Lactococcus lactis
were able to induce specific mucosal immune response. It will be a great
challenge how to make the recombinant Lactococcus lactis present heterologous
proteins to the mucosal immune system in an effective way and induce specific
immune response. One of the important directions for the further scientific
development in this field is exploring protein targeting system to express
heterologous antigens in precise locations of Lactococcus lactis. Expressing the
antigen and cytokine simultaneously in Lactococcus lactis is an attractive
direction as well. Using recombinant Lactococcus lactis that present antigens as
live mucosal vaccines provides an effective way to prevent microorganisms
invading and shows a promising future.
PMID- 17037081
TI - The new approaches to preservation of graft cell integrity in preservation for
transplantation.
AB - Restoration of cell plasma membrane integrity after injury is essential for the
survival of animal cells. In case of graft preservation or during chemotherapy in
cancer, cell membrane integrity and the process of its repair are disrupted.
Cytoprotective substances are important in such cases, as well as in other
diseases, for example in myocardial infarction, acute insults and in chronic
neurodegenerative diseases. Hyperosmolarity is a condition in which cell membrane
stability may be damaged in vivo but preserved in the in vitro conditions.
Hypertonicity causes water leaving from cells by osmosis, decreasing cell volume
and increasing of intracellular ionic strength. High intracellular ionic strength
perturbs cellular function by decreasing the rates of biochemical reaction. We
review the new experimentally studied cytoprotective substances and their
application in cell membrane protection. Moreover, we present our data on the
effects of hyperosmolarity and its protective effect on cell internal structure.
PMID- 17037082
TI - Contemporary methods for detection of microbial infections in transplanted
tissues.
AB - Infective processes developing after transplantation are diagnosed mainly in the
specimens harvested from blood and exudates. Not much attention has been focused
on identification of microorganisms present in the graft or penetrating the graft
from the recipient. Although a progress has been made with respect to detection
of viruses there is still little knowledge on the pathological role of bacteria,
transplanted together with the graft or acquired from the recipient, in evoking
or enhancing the rejection reaction (heterologous immune response). Recently
developing molecular techniques allow us to detect bacterial genetic materials in
clinical specimens. This article reviews commonly used methods for detection,
identification and typing bacterial pathogens. It focuses on specific and
universal methods based on gene sequencing, PCR and techniques based on
polymorphic DNA. We also present the examples of genes and microorganisms
analysed in laboratories. Together with conventional microbiological methods the
molecular tests can serve as a key for better understanding the bacterial
presence in tissues, not necessarily causing inflammation, quite often being
commensal, but also evoking host reaction under certain so far not defined
circumstances.
PMID- 17037084
TI - Sport for the transplant athlete-just harmless fun or a valuable tool?
AB - The persisting handicaps to full physical, mental and social rehabilitation in
the recipient of a successful transplant are outlined. The benefit derived from
sport with reference to the Transplant Games is summarized. An appreciation of
the papers in this issue of the Annals of Transplantation is given. They were
presented at the Second International Symposium on Sport and Transplantation held
in conjunction with The European Society of Organ Transplantation on October 19th
2005 in Geneva. The conclusion drawn is that the muscles of patients who have
suffered end stage disease of a vital organ do not recover rapidly or
spontaneously after a successful transplant and that the depression of VO2 Max
gives a documented indication of this fact. The good news, however, is that
appropriate physical activity and exercise is highly effective in overcoming the
deficit and sport is a vital component in the rehabilitation of the transplant
recipient.
PMID- 17037083
TI - The response of spleen dendritic cell-enriched population to bacterial and
allogeneic antigens.
AB - The dendritic cells (DC) play crucial role in initiation and modulation of immune
response especially innate immune response. We investigated the influence
bacterial (E. coli and S. epidermidis) and allogeneic antigens (heart, skin and
bone marrow transplants) on splenic DC- enriched population. We found that 1) the
in culture stimulation of rat splenic DC-enriched population by E. coli,
S.epidermidis, LPS and CpG DNA caused increase in class II-positive cells.
Simultaneously, a decrease in percentage of EDI, B cells and OX62 migrating DC
upon treatment with S.epidermidis was observed. LPS caused decreased frequency of
OX62 and NK cells. 2) Similarly to the in vitro the in vivo stimulation by E.
coli, S.epidermidis, LPS and CpG DNA increased the percentage of class II
positive cells. There was a decrease in the ED1, OX62 and B cell populations
following stimulation by S. epidermidis. 3) Mixed DC-enriched population and
donor PBM culture showed high level of response in both populations. 4) Syngeneic
and allogeneic transplants of heart, skin and BMC caused increase in class II
positive cells. Moreover, there was an increase in frequency of the ED1 and W3/13
populations after both syn- and allogeneic transplantation. The OX62 cells did
not react, whereas the B cell frequency rose only after allogeneic
transplantation. A significant decrease in NK cell population was noticed. 5) The
in vitro and in vivo bacterial stimulation brought about expression of TLR
receptors and Hsp. Mixed recipient DC with donor PBM culture caused expression of
Hsp 90 but not TLRs. Allogeneic stimulation by transplanted tissues did not evoke
expression of the investigated receptors and proteins. 6) Recipient DC-enriched
population produced IFN gamma upon stimulation with bacteria and skin but not
heart and BMC. Further studies on simultaneous stimulation of splenic DCs by
bacterial and allo-antigens will throw light on additive effects of bacterial
activation in allograft rejection.
PMID- 17037085
TI - Exercise following organ transplantation: A critical part of the routine post
transplant care.
AB - There are many reasons for recommendation of regular physical activity for organ
transplant recipients, including 1) Restoration of physical functioning following
deconditioning experienced prior to transplant; 2) Most patients are physically
inactivity, 3) The high prevalence of cardiovascular risk factors that may be
modified by regular physical activity; 4) Physical activity will optimize
physical functioning following transplant; and 5) p; hysical activity may reduce
or attenuate side effects of immunosuppression. There are many recommendations
for regular physical activity as an integral part of treatment of conditions that
are common to transplant recipients, including: hypertension management;
hyperlipidemia; Diabetes; and elevated cardiovascular disease risk. Transplant
recipients tolerate progressive exercise training well and can achieve levels of
functioning similar or higher than normal individuals. In order to optimize
functioning and overall health in organ transplant recipients, regular physical
activity should be prescribed and encouraged as a part of the routine post
transplant care.
PMID- 17037086
TI - Maintenance of the musculoskeletal mass by control of protein turnover: the
concept of anabolic resistance and its relevance to the transplant recipient.
AB - Although the overall size of the musculoskeletal mass is constrained by genetic
limitations, both the day to day maintenance and muscle wasting and
rehabilitation are regulated by protein synthesis (particularly the initiation
and elongation stages of translation) and by protein breakdown. These are
directly influenced by the nutritional state (size and composition of meals) and
type, mode and duration of exercise. In the context of food-related changes,
recent work has demonstrated that human muscle protein synthesis is almost
entirely controlled by the availability of essential amino acids and protein
breakdown by availability of insulin. Muscle protein synthesis is also markedly
stimulated by preceding exercise in a manner independent of but additive to any
effect of food. The sensing and signalling pathways within muscle are activated
by food and exercise in normal healthy subjects to elevate net muscle balance for
many hours after strenuous exercise. In many circumstances such as
immobilisation, ageing and many chronic diseases of the lung, kidney, heart, etc
(such as those often suffered by pre-transplant patients), the general
debilitation includes muscle wasting. In these subjects there appears to be a
general failure to respond adequately to food--so called "anabolic resistance".
It seems highly likely that this circumstance will also apply to transplant
recipients. It is also likely that anabolic resistance can be, to some extent,
reversed by regular physical activity which may "tune up" the anabolic pathways
to act in a more normal fashion. Nevertheless, the extent of re-growth and
adaptation of composition of muscle in transplant patients could be hindered by
drug treatment including the use of rapamycin (sirolimus) cyclosporine and
corticosteroids. These predictions should be tested by examining longitudinal
effects of different modes of exercise and nutritional regimens on rehabilitation
of muscle in transplant patients.
PMID- 17037087
TI - Exercising with a denervated heart after cardiac transplantation.
AB - Heart transplantation (HTR) is now an accepted life-extending procedure for those
dying of intractable heart failure (CHF). HTR patients expect a high quality of
life which implies a reasonable exercise capacity. Nevertheless HTR present
unique exercise challenges with both central and peripheral factors of limitation
that result in peak oxygen uptakes of 60-70% of age-matched normal subjects.
Among central factors persistent chronotropic incompetence questions the
occurrence and role of the graft reinnervation. Among peripheral factors the
energetic impairement of the skeletal muscle seem to result more from
microvascular abnormalities than from an actual deficit in oxidative capacity,
questioning the mechanism of recovery from the CHF peripheral myopathy and the
role of immunosuppressive drugs. Endurance and resistance training programs may
reverse at least in part most but not all of these abnormalities. Training
permits patients to engage in sports and even to participate in competitive
events that are rewarding to them but also to the community because it promotes
organ donation and confidence in medical achievements. Mechanisms of exercise
impairments and improvements resulting from training are discussed in the
perspective of current literature. Areas of future research and recommendations
for the practice of sports after HTR are suggested.
PMID- 17037088
TI - The T cell and NK cell immune response to exercise.
AB - Exercise elicits an increase in the numbers of circulating lymphocytes and
lymphocyte subsets (including NK cells) which is followed by a decrease in the
numbers of cells during recovery from exercise; this lymphocytopenia appears to
be due to a decrease in the percentage of type 1 T cells and NK cells in the
circulation at this time. A decrease in mitogen-stimulated T cell proliferation
and T cell production of IL-2 and IFN-gamma is reported immediately after acute,
intensive exercise. NK cell cytolytic activity per cell (NKCA) does not appear to
change much after exercise unless the bout was prolonged, intense and stressful,
in which case NKCA can be depressed for several hours. Resting immune function is
not very different in athletes compared with non-athletes. However, periods of
intensified training in already well trained athletes can result in a depression
of immunity in the resting state which may be due to the cumulative effects of
repeated bouts of intense exercise with the consequent elevation of stress
hormones, particularly cortisol and anti-inflammatory cytokines (e.g. IL-6, IL
10, IL-Ira) causing temporary inhibition of type 1 T cell cytokine production
with a relative dampening of the type I (cell-mediated) response.
PMID- 17037089
TI - Exercise and the brain: insight in new therapeutic modalities.
AB - Physical exercise influences the central dopaminergic, noradrenergic and
serotonergic systems. A number of studies have examined brain noradrenaline (NA),
serotonin (5-hydroxytryptamine, or 5-HT) and dopamine (DA) with exercise.
Although there are great discrepansies in experimental protocols, the results
indicate that there is evidence in favour of changes in synthesis and metabolism
of monoamines during exercise. The last five to ten years the microdialysis
technique is used to explore neurotransmitter release during exercise.
Microdialysis can collect virtually any substance from the brains of freely
moving animals with a limited amount of tissue trauma. It allows the measurement
of local neurotransmitter release in combination with on-going behavioral changes
such as exercise. Microdialysis probes were implanted in different brain areas to
monitor diverse aspects of locomotion (striatum, hippocampus, nucleus accumbens,
frontal cortex, spinal cord), food reward (hypothalamus, hippocampus, cerebral
cortex), thermoregulation (hypothalamus),... Although the relationship between
physical activity and mood has long been recognized, the use of exercise training
as a treatment for clinical depression has been the focus of rigourous study only
recently. The available evidence provides considerable support for the value of
exercise in reducing depressive symptoms both in healthy and clinical
populations. Subsequently, many studies have shown that environmental stimulation
such as 'enriched environment' and spontaneous activity elicits various plastic
responses in the adult brain of rats. Several molecular systems such as
neurotrophic factors, could potentially participate in the benefits of exercise
on the brain. Several experiments indicate that voluntary wheel running in rats
increases both cell proliferation and recruitment of new neurons in several brain
areas. Exercise is a powerful tool to stimulate several brain processes, and it
is becoming clear that therapeutic effects of exercise are not only good for
cardiovascular and other diseases, but that exercise is also good for the brain.
PMID- 17037090
TI - The limits of human athletic performance.
AB - For each individual, there is a limit to the capacity to perform exercise. The
limitation, however, depends on the nature of the task and is also influenced by
a number of other factors. Muscle strength is determined largely by muscle mass,
specifically muscle cross-sectional area, but is also influenced by neural drive
and biomechanical factors. Endurance performance depends on both cardiovascular
capacity and the metabolic characteristics of the skeletal muscles. These factors
are determined in part by genetic endowment: the elite sprinter has a high
proportion of Type 2 muscle fibres while the leg muscles of the successful
marathon runner are composes mainly of Type 1 fibres. Whatever the genetic
potential, expression of this depends on the intensity, duration and frequency of
the applied training stimulus, diet and other factors. The limitation may also
depend on environmental factors, such as altitude and temperature.
PMID- 17037091
TI - Prope tolerance in organ grafting.
PMID- 17037092
TI - Cadaveric organ donation following transplant games events.
PMID- 17037093
TI - A transplant athlete's perspective.
PMID- 17037094
TI - Pancreas after kidney (PAK) transplantation--first case in Poland.
AB - Transplantation of pancreas is a generally accepted treatment option for patients
with type 1 diabetes mellitus. This procedure restores physiological insulin
secretion, resulting in long-term normoglycemia and preventing complications of
diabetes. One of the therapeutic possibilities is pancreas after kidney
transplantation (PAK) for patients with previous successful kidney
transplantation. There is evidence that patient and kidney graft survival is
higher in PAK compared with diabetic recipients of kidney or pancreas alone
(PTA). We report a case of pancreas after kidney transplantation in a 38 year-old
male with type 1 diabetes mellitus of 21 year duration. One year before PAK he
received cadaveric kidney transplant. Pancreatic graft was placed on the left
side of the pelvis and enteric drainage was used. Immunosuppression consisted of
antithymocyte globulin (ATG), daclizumab, tacrolimus, mycophenolate mofetil, and
steroids. Ten months after surgery the patient stays normoglycemic, insulin
independent with good kidney function (Cr-1,5 mg/dl).
PMID- 17037096
TI - [Is the developmental model accurate for all psychiatric disorders?].
AB - In the 1980's a neurodevelopmental hypothesis of schizophrenia was proposed.
Since that time, the role of early developmental age as a risk period for action
of etiological factors in psychosis was confirmed. Additionally, many
disturbances of pre-schizophrenic persons in the developmental age were
demonstrated. Recently published longitudinal cohort studies indicate that
majority of the psychiatric disorders other than schizophrenia are preceded by
occurrence of psychiatric disorders in childhood and early adolescence. Moreover,
in numerous studies of adult anxiety and mood disorders, the role of early risk
factors was observed and temperament, neurophysiological and psychopathological
disturbances in early age were reported. The resulting developmental model of
psychiatric disorders may help in the understanding of their pathogenesis.
Subsequently, detection and treatment of early life disturbances may
hypothetically prevent severe psychopathological symptoms in adulthood.
PMID- 17037095
TI - [Current problems in psychiatric health care in Poland (2005)].
AB - The paper is a presentation of the most important and actual psychiatric health
care problems in Poland: the financial situation of hospitals, the risk faced by
the out-patient psychiatric care,ethical problems related to clinical practice,
as well as issues on postgraduate education.
PMID- 17037097
TI - [Disturbances of social cognition in schizophrenia].
AB - Social cognition is an ability to perceive socially relevant stimuli and to
behave accordingly. It is connected with the processing of information brought
about by significant social stimuli. Recently, social cognition is a topic of
intensive research in psychology, neurosciences and psychiatry. Processes
involved in social cognition include: perception of emotion, input of eye
contact, reaction to voice prosody or decision-making in social situations. A
particular role is played by the mentalizing capabilities (mind-reading) i.e.
ability to interpret behaviour of others by attributing them certain mental
states. Such an ability is often conceptualized as the Theory of Mind (ToM). This
paper is a review of issues connected with disturbances of social cognition in
patients with schizophrenia. Deficits in perceptions of face emotion and
disturbances of Theory of Mind function in schizophrenia were discussed with
special regard to their potential role as endophenotypes of vulnerability to
schizophrenia. Also, relations between social cognition and basic neurocognitive
processes were presented, as well as the effect on social cognition of different
methods of schizophrenia treatment.
PMID- 17037098
TI - [Analysis of the seasonality of birth effect in schizophrenic patients in Poland
with the application of the seasonal decomposition method].
AB - INTRODUCTION: Seasonality of the birth of patients diagnosed with schizophrenia
is one of the most repetitive phenomena in epidemiological studies on this
illness. The paper presents a review of the literature, with an emphasis on the
research findings and development of methods used to investigate the phenomenon.
AIM: The aim of the study was to analyze the phenomenon of birth seasonality in
schizophrenic patients in the Polish population, using new methods of the
seasonal decomposition analysis. METHODS: The study utilized birth dates of
13,668 patients diagnosed with schizophrenia according to the ICD-10 criteria,
and discharged from all psychiatric hospitals in Poland in the years 1997-2000.
The data on live births in the general population as published by the Main
Statistical Office served as the reference group. 7,432,803 people were born in
Poland in the years 1964-1976. Efforts were made to minimize the age-related
incidence effect. In order to eliminate seasonal variations resulting from
deviations in the number of births in the general population, an indicator of the
number of births of patients diagnosed with schizophrenia per 10 thousand live
births in the general population was created. A time series of 156 monthly
observations covering the period of 13 years was produced. The data were analyzed
using the Census II X- 11 method, one of the most recent methods to analyze time
series and seasonal decomposition. RESULTS: The results confirm a 5-8% birth
excess for schizophrenia in December and January.
PMID- 17037099
TI - [Dispute over the multiple personality disorder: theoretical or practical
dilemma?].
AB - Dissociative identity disorder (DID) could also be referred to as multiple
personality disorder (MPD). Due to rare occurrence and difficulty in its'
identification it is infrequently diagnosed in Poland. The indicated disorder has
been portrayed by the authors throughout the historical context, referring to
initial 18th century's references concerning dissociation. A typical
dissociatively disordered person has been characterized along with his individual
personality categories such as: original personality, altered personality, host
and personality fragment. Moreover various diagnosis criterions of DID have been
introduced. DID has also been differentiated with other disorders: PTSD (post
traumatic stress disorder) and BPD (borderline personality disorder). A
hypothesis has been set up, stating that DID is directly correlated with the
trauma experienced during childhood, while PTSD is linked with traumatic lived
through events in the later period of ones' life. The most contemporary and
frequently used research tools for DID have been indicated: dissociative
experience scale (DES) and somatoform dissociation questionnaire (SDQ-20). Based
upon the known literature, the authors have presented treatment methods such as
hypnotherapy and recorded therapy sessions. It is the view of the authors that
the switching in dissociative identity disorder is of adaptive character (it
occurrs depending upon adaptive needs).
PMID- 17037100
TI - [Problem-solving strategies and marital satisfaction].
AB - AIM: This study investigated the relation between problem-solving strategies in
the marital conflict and marital satisfaction. METHOD: Four problem-solving
strategies (Dialogue, Loyalty, Escalation of conflict and Withdrawal) were
measured by the Problem-Solving Strategies Inventory, in two versions: self
report and report of partners' perceived behaviour. This measure refers to the
concept of Rusbult, Johnson and Morrow, and meets high standards of reliability
(alpha Cronbach from alpha = 0.78 to alpha = 0.94) and validity. Marital
satisfaction was measured by Marriage Success Scale. The sample was composed of
147 marital couples. RESULTS: The study revealed that satisfied couples, in
comparison with non-satisfied couples, tend to use constructive problem-solving
strategies (Dialogue and Loyalty). They rarely use destructive strategies like
Escalation of conflict or Withdrawal. Dialogue is the strategy connected with
satisfaction in a most positive manner. These might be very important guidelines
to couples' psychotherapy. Loyalty to oneself is a significant positive predictor
of male satisfaction is also own Loyalty. CONCLUSION: The study shows that
constructive attitudes are the most significant predictors of marriage
satisfaction. It is therefore worth concentrating mostly on them in the
psychotherapeutic process instead of eliminating destructive attitudes.
PMID- 17037101
TI - [Bright light therapy in pregnant women depression--3 case studies].
AB - AIM: Bright light therapy (BLT) is a new method of biological treatment in
psychiatry. Good tolerance makes it an attractive method used not only in
seasonal affective disorder. An episode of depression during pregnancy may be a
new indication. The study aimed to describe effects of treatment of depression in
3 pregnant women. METHOD: The women were out-patients in their 6-th, 7-th and 8
th months of pregnancy and diagnosed with depression according to ICD-10
criteria. The treatment was a morning exposure to 1 hour 5 000 LUX bright light
from Monday to Friday. The antidepressant effect was assessed after the 2nd and
4th week of BLT. Side effects of BLT were monitored over the whole BLT treatment
period. RESULTS: The mean improvement of depressive symptoms after 2 and 4 weeks
of BLT was 33% and 55%, respectively. Side effects were not observed in any of
the patients. CONCLUSIONS: Morning BLT seems to be an effective and a very well
tolerated mode of treatment of pregnant women suffering from non-seasonal
depression. The manner and length of BLT maintenance treatment requires further
studies.
PMID- 17037102
TI - [Correlation between depressive and anxiety symptoms, distress and functioning].
AB - AIM: The aim of the study was to define the correlation between
anxiety/depressive symptoms, distress and functioning. METHOD: The research is
based on the analysis of 104 persons (65 women, 39 men), who were patients of
psychiatrists (42 persons), or general physician attenders (62 persons)
complaining of anxiety or depressive symptoms. Distress was estimated with the
General Health Questionnaire (GHQ-30), psychopathological symptoms and diagnoses
were evaluated with the Present State Examination (PSE) and the level of
functioning with Global Assessment of Functioning (GAF). The intensity of ICD-10
symptoms was calculated for: generalized anxiety disorder, agoraphobia, social
phobia, panic disorder, depressive disorder and dysthymia. RESULTS: The lowest
score of distress was found in the group with sub-clinical, sole anxiety or
depressive symptoms. An intermediate level was present in the group with anxiety
and mixed anxiety-depressive disorders, and the highest in the group with
depression. The functioning scores were in an inverse order. CONCLUSIONS: The
differences in scores of distress and functioning between groups of patients with
anxiety disorders, mixed anxiety-depressive disorders and depression are
dependent on the intensity of depressive symptoms and are independent of the
intensity of anxiety symptoms.
PMID- 17037103
TI - [The present application and the perspective progress of cognitive-behavioural
therapy].
AB - The article presents the basic principles of cognitive-behavioural therapy and
its applications in treating depression, anxiety disorders, post-traumatic stress
disorder (PTSD) and addictions. The possibility of using cognitive-behavioural
interventions for chronic somatic diseases (ischaemic heart disease, skin
diseases, insomnia, migraine and chronic prostatitis) are also suggested.
PMID- 17037104
TI - [Sense of coherence, personality and style of coping by patients suffering from
depressive disorders].
AB - INTRODUCTION: At present increasing medical attention is paid to the
salutogenesis approach suggested by Aaron Antonovsky. The main focus of interest
in the approach is the sense of coherence. AIMS: The aim of the study was to
define the sense of coherence and the mutual condition linked between this sense
and some personality traits within an individual, including the styles of coping
by men and women suffering from depression. MATERIAL AND METHODS: The research
included the use of a SOC-29 questionnaire, NEO-FFI test and Moos' test. The
research was conducted on 69 patients recognized to have suffered from
depression. The patients were in treatment at The Psychiatric and Neurosis
Disorder Clinic with Critical Intervention Ward, Medical University of Lodz.
RESULTS: 1) A sense of coherence within an individual is considerably stronger in
male patients. 2) Males and females differ in the realm of particular personality
traits and the ways of dealing with every day problems. 3) Character traits and
the ways to handle stressful situations differ among individuals in respects to
the sense of coherence level within an individual.
PMID- 17037105
TI - [The impact of personal resources on coping with stress in climacteric women].
AB - Climacterium is a physiological (so absolutely normal) occurrence in a woman's
life. Menopause is not a disease but some women have somatic and/or psychic (for
example: stress related) problems connected with this life-stage transition. The
presented study examined stress-coping strategies and personal coping resources
(optimism, emotional control, sense of self-efficacy, sense of self-worth and
sense of life satisfaction). Fifty post menopause women completed the
psychological questionnaires. Conclusions will be presented.
PMID- 17037106
TI - [Present and premorbid self-image in patients with coronary heart disease].
AB - AIM: The aim of this study was to find the differences between premorbid and
present self-image in patients with coronary heart disease. METHODS: 70 patients
with stable coronary heart disease treated at the Internal Medicine Department of
the Military Hospital in Lublin and 70 healthy controls were studied. Mean age of
the investigated patients was 53.11 years. 77% of the studied patients were city
inhabitants and 23% were countryside dwellers. Subjects were studied with the use
of the State-Trait Anxiety Inventory, by the Adjective Check List (ACL) and a
questionnaire designed especially for the study of sociodemographic data of the
investigated patients. Premorbid and present self-images were compared with the
use of the ANOVA test. RESULTS: Our results showed that there are statistically
significant differences between premorbid and present self-image in the
perception of patients with coronary heart disease. CONCLUSIONS: 1. In present
self-image, compared to the premorbid one, patients with coronary heart disease
have low self-esteem, greater fear about the future, low endurance in performing
tasks, they are less enterprising, have lower ability to overcome stress, they
are more dependent and have a greater need to look for safety. 2. Women with
coronary heart disease perceive themselves as having low self-esteem, low self
trust, more difficulties in overcoming stress and a lower ability to understand
other people's behaviour as compared to the time before the disease. 3. Men with
coronary heart disease perceive themselves as having less endurance, being less
enterprising, having a negative attitude towards themselves and other people and
being more dependant compared to the time before the illness.
PMID- 17037107
TI - [Psychological aspects of heart transplantation].
AB - The most important rules of heart transplantation qualification as well as the
factors which burden patients who are treated with this method are discussed in
the article. Particularly difficult moments for patients arethose of decision
making regarding the transplantation, which is accompanied with fear, and
sometimes associated with ethical or religious doubts, subsequently--the stress
related to the time waiting for the operation, and thereafter, the rehabilitation
demanding patient's co-operation. The difficulties associated with living with a
transplanted heart refer to regular immunosuppressive treatment, follow-up
visits, avoiding infections, withdrawal from drinking alcohol and smoking
cigarettes, living in a healthy life-style. The person with a transplanted heart
has to acquire a series of skills and perform a lot of tasks associated with
following doctor's appropriate advises.
PMID- 17037108
TI - [Sociodemographic factors and their influence on anxiety and depression in
patients after limb amputation].
AB - AIM: The aim of this study was to assess the score of HADS and the correlation
with sociodemographic factors and personality traits in patients after limb
amputation. METHOD: 45 patients after limb amputation due to atherosclerosis and
30 persons from a control group participated in the study. HADS Scale and the
Maudsley Personality Inventory created by Eysenck were used in the study.
Socidemographic data were collected by means of the Sociodemographic data
questionnaire. RESULTS: In comparison to the control group, patients after limb
amputation achieved a higher score in HADS-A and HADS-D and in the N scale of the
Maudsley Personality Inventory. Higher levels of anxiety and depression were
noticed in patients suffering from phantom limb pain and in patients with
neurotic personality traits. CONCLUSION: Patients after limb amputation need
multidisciplinary care because of higher levels of anxiety and depression
(especially patients with phantom limb pain and those with neurotic personality
traits).
PMID- 17037109
TI - [Personality types in patients after vertebral surgery].
AB - AIM: To compare personality types in patients after vertebral surgery. METHOD: 74
patients after vertebral surgery were examined with the MPI. 22 patients were
operated because of injury. 52 patients were operated because of chronic pain
back. The control group consisted of 20 healthy people. Maudsley Personality
Inventory created by Eysenck, was used to study personality types. RESULTS: There
were no differences in personality types between patients suffering from chronic
back pain and patients operated because of injury. Statistically, a significantly
higher score in the N scale was noticed in the group with chronic back pain in
comparison to patients operated because of injury and in comparison to the
control group. CONCLUSIONS: A higher score in the N scale observed in patients
suffering from chronic back pain, may suggest a specific personality type of
those patients. Higher level of neuroticism may create some difficulties in the
acceptation of the illness and adaptation process. It is necessary to take
special psychological care of those patients.
PMID- 17037110
TI - The best methods of preventing falls in hospitals.
PMID- 17037111
TI - Strategies for moving beyond the illness in early schizophrenia and in chronic
kidney disease.
AB - Although the literature suggests that loss of self is a universal concern across
chronic illnesses in general, little consideration has been given to loss of self
across physical and mental illnesses. The authors compare loss of self in
individuals with a mental illness (early schizophrenia) and in those with a
physical illness (chronic kidney disease). In this secondary analysis, focus
group data from 2 samples are examined for similarities and differences in the
emergent themes. While striving to be my best self getting on with life was an
overarching goal for both groups, the strategies for achieving it differed. The
participants engaged in activities related to approaching the illness,
accommodating, and connecting in order to strike a balance between the demands of
the illness and non-illness aspects of their lives. The commonalities in the wish
to be my best self that were found in both groups indicate that the wish to
preserve a sense of self beyond the illness may not be illness-specific. The
preliminary results of this secondary analysis suggest that building a positive
sense of self in the face of illness is a critical part of illness adjustment and
that there are opportunities for nurses and researchers to learn about the
spectrum of strategies employed by individuals as they strive to move beyond the
illness.
PMID- 17037112
TI - A six-month profile of community case coordinated older adults.
AB - The purpose of this study was to assess the needs of older case coordinated
clients receiving community health services, by examining changes in cognitive
status, physical and mental health status, social support, risk for
institutionalization, and service use over a 6-month period from initial intake
into home care. Significant predictors of professional and supportive home care,
as well as emergency room use and hospital days, were also examined. Standardized
interviews were conducted with 234 clients at the time of referral; follow-up
interviews were conducted with 179 of these clients after 6 months of case
coordination. Results reveal that physical and mental health improved, while
cognitive status remained stable. Although social interaction and instrumental
support decreased, subjective support remained stable. Risk of
institutionalization decreased. Occupational therapy, nursing, and homemaking
were the most frequently used services. The best predictor of professional and
supportive home care was a risk of institutionalization score. The needs of this
older adult population changed even within the relatively short span of 6 months.
Frequent review of needs in some form may be warranted in order to maintain
effective service plans.
PMID- 17037113
TI - Barriers to population-focused health promotion: the experience of public health
nurses in the province of Manitoba.
AB - There is growing evidence that population health is influenced by broad socio
environmental factors that require population-focused health promotion
strategies. The author reports on a study of the perspectives of public health
nurses (PHNs) on the nature of their health promotion practice in the Canadian
province of Manitoba, highlighting their perceptions about barriers to population
focused health promotion. A descriptive, exploratory research design was used to
conduct standardized open-ended interviews with 24 PHNs in 3 geographically and
demographically diverse health authorities. There were remarkable similarities in
PHNs' perceptions about their practice. Three categories of barrier to population
focused health promotion were identified: barriers at the level of individual
PHNs; organizational barriers (culture, policies, processes); and extra
organizational barriers at the level of the community or province. The results
point to a gap between the theory that population-focused health promotion is at
the heart of PHN practice and the experience of PHNs at the 3 sites. A concerted
effort to address the barriers is needed so that PHNs in Manitoba can play a
leadership role in creating a health-care system that truly invests in population
health.
PMID- 17037114
TI - Incidents in a psychiatric forensic setting: association with patient and staff
characteristics.
AB - Patient-related incidents are of particular concern for those working with
forensic psychiatric populations. Evidence suggests that personality, stress, and
burnout of nursing staff are predictive of incidents. However, the exact
relationship of these factors with staff-patient interactions and the incidents
that occur within these interactions have not been thoroughly explored. The
authors collected data on the nature of incidents on a forensic unit within a
psychiatric hospital over a 1-year period, as well as data on the characteristics
of 13 staff members. They found that 10% of patients were responsible for 58% of
the incidents. Patients with a diagnosis of schizophrenia were disproportionately
involved in incidents. The frequency of non-violent incidents varied among
nursing teams to an extent greater than that expected by chance. A relationship
between incidents and some staff characteristics was also found. These results
highlight the need for further research into the incidents that occur in
situations where patient attributes, nurse attributes, and environmental factors
produce complex interactions.
PMID- 17037115
TI - The searching, processing, and sharing of breast cancer information by women
diagnosed with the illness.
AB - Most women diagnosed with breast cancer seek health-related information to cope
with the demands of the illness. However, few studies have documented how women
actually seek, process, and share cancer-related information. This qualitative
study explores the process of managing cancer-related information from the
perspective of 12 women with breast cancer. Three core components of information
management (IM) emerged from the data: initial cancer-related informational
triggers, emotional and behavioural reactions to the information, and the IM
outcomes of feeling relieved, hopeful, supported, or distressed. According to the
participants, IM is an ongoing process in which the choice to continue sharing
cancer-related information with individuals depends on women's perceptions of how
supportive they have been.
PMID- 17037116
TI - Field testing the WHOQOL-100 in Canada.
AB - The purpose of this project was to test the WHOQOL-100, an instrument for
assessing quality of life (QOL), developed to facilitate cross-cultural
comparison. The instrument was tested with a convenience sample of 144 people.
The mean age of participants was 58 years and 41% were female.Test-retest
reliability was .86 for the physical domain, .78 for the psychological domain,
.91 for independence, .87 for social relationships, .77 for environment, and .60
for spirituality. Consistency reliability was .77 for physical, .79 for
psychological, .89 for independence, .71 for social relationships, .80 for
environment, and .89 for spirituality/ personal beliefs. Correlations of the
various domains with other instruments, including the SF-36, the Self-Anchoring
Striving Scale, and the Visual Analogue Scale for Pain, supported the convergent
validity of the instrument. The instrument was able to discriminate between
healthy and ill populations, providing support for construct validity.
PMID- 17037117
TI - Self-care from the perspective of people living with diabetes.
AB - This review presents findings from a critical integrative review of research into
barriers to and facilitators of self-care from the perspective of people with
diabetes. The review was motivated by a perceived need to understand self-care
from the perspective of those living with this chronic disease and to explore the
implications of this understanding for health-care policy in Canada. Journal
manuscripts and dissertations exploring self-care from the perspective of adults
with type I or type II diabetes and published in English between 1993 and 2003
were reviewed. Both quantitative and qualitative studies were included. Studies
were informed by varying definitions of self-care and facilitators and barriers
emerged accordingly. An overarching thematic tension was evident, based on a view
of self-care as revolving around the disease or evolving in the lives of people
with diabetes. This tension has implications for health professionals and for
those involved in policy development related to self-care.
PMID- 17037118
TI - Canadian Academy of Health Sciences.
PMID- 17037119
TI - Crosslinguistic perspectives on the development of prosodic words.
PMID- 17037120
TI - Word-minimality, epenthesis and coda licensing in the early acquisition of
English.
AB - Many languages exhibit constraints on prosodic words, where lexical items must be
composed of at least two moras of structure, or a binary foot. Demuth and Fee
(1995) proposed that children demonstrate early sensitivity to word-minimality
effects, exhibiting a period of vowel lengthening or vowel epenthesis if coda
consonants cannot be produced. This paper evaluates this proposal by examining
the development of word-final coda consonants in the spontaneous speech of four
English-speaking children between the ages of one and two. Although there was no
evidence of vowel lengthening, coda consonants were more accurately produced in
monosyllabic target words with monomoriac vowels, suggesting earlier use of coda
consonants in contexts where they can be prosodified as part of a bimoraic foot.
One child also showed extensive use of vowel epenthesis and coda consonant
aspiration concurrent with the production of codas. However, we show that this
was due to the articulatory challenges of producing complex syllable structures
rather than an attempt to produce well-formed minimal words. These results
suggest that learners of English may exhibit an early awareness of moraic
structure at the level of the syllable, but that language-specific constraints
regarding word-minimality may be acquired later than originally thought.
PMID- 17037121
TI - Grammar and frequency effects in the acquisition of prosodic words in European
Portuguese.
AB - This paper investigates the acquisition of prosodic words in European Portuguese
(EP) through analysis of grammatical and statistical properties of the target
language and child speech. The analysis of grammatical properties shows that
there are solid cues to the prosodic word (PW) in EP, and the presence of early
word-based phonology in child speech shows that EP children are aware of these
cues. It is thus hypothesized that grammatical properties could play a role in
the development of the PW by promoting the early production of the different word
shapes found in the language. The analysis of statistical properties of the
input, namely word shape frequencies in adult speech and child-directed speech,
shows that they constrain early word shapes in child speech in ways similar to
recent reports on other languages: a fairly high frequency of monosyllabic
shapes, and especially of monosyllabic CV shapes, in the input agrees with the
production of subminimal words in child speech; a fairly high frequency of
trisyllabic and larger shapes in the input (adult speech in particular) matches
the early development of words larger than a binary foot. These patterns,
together with the co-occurrence of truncation to subminimal shapes in the initial
and later stages, as well as the presence of prosodic fillers regardless of word
size, support the claim that early words in EP are not constrained by minimality
or maximality requirements. The potential interaction of grammar and frequency
effects in PW acquisition is discussed in the light of the present findings and
comparable data available in the literature for English, French, Spanish and
Catalan.
PMID- 17037122
TI - The acquisition of prosodic word structures in Spanish by monolingual and Spanish
German bilingual children.
AB - This article examines the constraints on Prosodic Word production in Spanish by
three monolingual and three Spanish-German bilingual children from the beginning
of word production until 2;2. It also considers the relationship between Prosodic
Words and Phonological Phrases, and in the case of monosyllabic words, it takes
into consideration syllable structure (i.e., presence or absence of codas), in
order to ascertain the importance of foot binarity in early child speech.
Although the preferred Prosodic Word shape is that of a trochee, there appear a
few monosyllables, consisting of CVC (or CV), which are produced earlier by the
bilinguals than by the monolinguals. The minimality constraint is violated by the
production of CV forms. Maximality constraints are observed for a very short
time, as unfooted syllables appear very soon, especially in the data of the
monolinguals. However, it takes several more months until Spanish children are
able to produce Prosodic Words containing two feet, whereas Phonological Phrases
constituted by two disyllabic Prosodic Words are produced earlier by some
children. It is proposed that such data can be optimally treated by means of
constraints, and their relevance to the question of whether prosodic structure is
acquired bottom-up is briefly discussed.
PMID- 17037123
TI - The relevance of metrical information in early prosodic word acquisition: a
comparison of Catalan and Spanish.
AB - This paper focuses on the development of Prosodic Word shapes in Catalan, a
language which differs from both Spanish and English in the distribution of PW
structures. Of particular interest are the truncations of initial unstressed
syllables, and how these develop over time. Developmental qualitative and
quantitative data from seven Catalan-speaking children reveal that maximality
constraints are active at two stages, namely, the moraic trochee stage, and the
bisyllabic foot stage. One of the noteworthy differences between Catalan and
Spanish is the rate of acquisition of weak initial syllables in WS words, as
Catalan learners omit initial syllables in WS target iambs for a significantly
longer time than Spanish learners, despite the fact that Catalan is a language
where the bisyllabic iambic WS pattern is more frequent than in Spanish. We claim
that this asymmetry in the course of development of PWs can be attributed to the
frequency of exposure to different metrical models. In Catalan (and also in
English), the high frequency of CVC structures boosts the availability of the
moraic trochee in initial stages. Thus the data provide crucial evidence that
children at early stages of PW production are especially sensitive to the
frequency distribution of foot structure in the input. In general, the behavior
of Catalan PW acquisition significantly supports the idea that the course of PW
development is strongly influenced by language-specific distributions of prosodic
structures (especially feet) in the target language (see Demuth, 1996a, 2001a,
2003; Lleo, 2002; Prieto, Bosch-Baliarda, and Saceda-Ulloa, 2005; and Zamuner,
Gerken, and Hammond, 2004, among others).
PMID- 17037124
TI - Input frequency and word truncation in child Japanese: structural and lexical
effects.
AB - Recent research indicates that the statistical properties of the input have an
impact on the prosodic shape of young children's word production. However, it is
still not clear whether the effects of input statistics emerge from the frequency
of prosodic structures or the frequency of individual lexical items. This issue
is investigated in this study by analyzing cases of word truncation spontaneously
produced by three Japanese-speaking children (1;5-2;1) and the frequencies of
relevant words and prosodic word structures produced by their mothers. A
significant correlation was found between children's truncation rates for
individual target words and the frequency of the same words in the maternal
input, but not between the truncation rates for different prosodic word
structures and the frequencies of the corresponding structures in maternal
speech. The size and shape of truncated outputs were better explained in terms of
their correspondence to the target structures than the frequencies of shorter
forms in the input. The results indicate that variation in early word truncation
is systematically related at least to the lexical frequency of the target words,
and that input frequency has a clearer connection to what truncates than how it
truncates.
PMID- 17037125
TI - Characterisation of the biosand filter for E. coli reductions from household
drinking water under controlled laboratory and field use conditions.
AB - More than a billion people in the developing world lack access to safe and
reliable sources of drinking water. Point of use (POU) household water treatment
technology allows people to improve the quality of their water by treating it in
the home. One emerging POU technology is the biosand filter (BSF), a household
scale, intermittently operated slow sand filter. Laboratory and field studies
examined Escherichia coli reductions achieved by the BSF. During two laboratory
studies, mean E. coli reductions were 94% and they improved over the period of
filter use, reaching a maximum of 99%. Field analysis conducted on 55 household
filters near Bonao, Dominican Republic averaged E. coli reductions of 93%. E.
coli reductions by the BSF in laboratory and field studies were less than those
typically observed for traditional slow sand filters (SSFs), although as for SSFs
microbial reductions improved over the period of filter use. Further study is
needed to determine the factors contributing to microbial reductions in BSFs and
why reductions are lower than those of conventional SSFs.
PMID- 17037126
TI - Does improved access to water supply by rural households enhance the concept of
safe water at the point of use? A case study from deep rural South Africa.
AB - The concept of safe water is defined by three principles: the health-related
quality must be suitable, the supply/source must be accessible and the water must
constantly be available in quantities sufficient for the intended use. If any one
(or more) of these three elements is missing from a water services improvement
programme, providing safe water is not successfully achieved. A study in a deep
rural area in South Africa showed that providing small communities, using
untreated river water as their only water source, with good quality water through
a piped distribution system and accessible at communal taps did not fall within
our parameters of safe water. The parameters for measuring the three principles
were: absence of Escherichia coli in drinking water samples; accessibility by
improving tap distances to within 200 m from each household; availability by
assessing whether households have at least 25 L per person per day. Results show
that although E. coli levels were reduced significantly, households were still
consuming water with E. coli numbers at non-compliant levels. Access (distance)
was improved from an average of 750 m from households to river source to an
average of 120 m to new on-tap source points. This did not result in significant
increases in household quantities, which on average remained around 18 L per
person per day.
PMID- 17037127
TI - Predictive input parameters for enteric virus presence at the inlet of a potable
water supply.
AB - Kentucky river water samples were collected at the input of a potable water
supply weekly, for a period of two years. Eighteen parameters were analysed
and/or recorded for each weekly observation. The variables were of a physical,
chemical and biological nature. Enteric virus presence was detected by cell
culture analysis from approximately 200 L samples of river water. A database of
108 observations was assembled. Of these only 100 complete observations were used
for the modelling analysis. Model input parameters were selected solely based on
their statistical significance in forward, backward and stepwise selection
procedures. Multivariate logistic regression (MLR) was used to determine the
relative significance of the input parameters for predicting the presence or
absence of enteric virus. The final, best-fit MLR model that used log-transformed
values for enterococci, the AC/TC ratio, faecal coliforms (FC) and temperature
demonstrated 82.5 and 81.4% sensitivity and specificity, respectively.
PMID- 17037128
TI - Removal of cyanobacteria, cyanotoxins, heterotrophic bacteria and endotoxins at
an operating surface water treatment plant.
AB - The removal of cyanobacteria, hepatotoxins produced by them (microcystins),
phytoplankton, heterotrophic bacteria and endotoxins were monitored at a surface
water treatment plant with coagulation, clarification, sand filtration,
ozonation, slow sand filtration and chlorination as the treatment process.
Coagulation-sand filtration reduced microcystins by 1.2-2.4, and endotoxins by
0.72-2.01 log10 units. Ozonation effectively removed the residual microcystins.
The treatment process reduced phytoplankton biomass by 2.2-4.6 and heterotrophic
bacteria by 2.0-5.0 log10 units. In treated water, the concentration of
microcystins never exceeded the WHO guide value (1 microg/L), but picoplankton
and monad cells were often detected in high numbers. The heterotrophic bacterial
isolates from the treated waters belonged to genera Sphingomonas, Pseudomonas,
Bacillus, Herbaspirillum and Bosea.
PMID- 17037129
TI - Accumulation of copper and silver onto cell body and its effect on the
inactivation of Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa, a gram-negative rod bacterium, is a causative agent of
waterborne pneumonia and presents high tolerance against conventional
disinfectants. The inorganic biocidal reagents, copper and silver, were applied
to inactivate P. aeruginosa inoculated in a synthetic drinking water (SDW).
Additionally, the relationship of the specific amount of accumulated copper and
silver reagents (Cs) on P. aeruginosa with inactivation profile was elucidated in
this study. Flow cytometry (FCM) following staining with SYTO 9 and PI was used
for detection of bacterial viability and density. Individual copper and silver
reagents, and their combination, exhibited excellent biocidal abilities even at
the concentration of 0.05 mgCu/L and 0.005 mgAg/L. The critical amounts of
accumulated disinfectant (Cs) were calculated at 2.82 x 10(-7) microgCu/cells and
5.13 x 10(-8) microgAg/cells; at an incubation of 70 h. Consequently, the role of
disinfectant on the inactivation of P. aeruginosa and the assessment of biocidal
ability of copper, silver, and their combination were successfully explained by
evaluating the terms Cs and Cc.
PMID- 17037130
TI - Combined use of microbiological and non-microbiological data to assess treatment
efficacy.
AB - The treatment efficacy for reducing Campylobacter concentrations by a drinking
water treatment plant was assessed using a stochastic Monte Carlo model. The goal
of the study was to reduce uncertainty of the results by combining
microbiological and non-microbiological data in an advanced treatment assessment.
Combining raw water Campylobacter and E. coli data reduced the uncertainty on raw
water (peak) concentrations five-fold. Similar improvement was achieved for rapid
sand filtration. Ozone disinfection was modelled based on ozone concentrations,
contact time and temperature. Since this data was available, whereas most
microbiological analyses at this point were negative, uncertainty was reduced
three-fold. The slow sand filtration assessment could not be improved; however,
since previous steps contained less uncertainty, this did not increase
uncertainty by much. The study showed that using appropriate data for each
treatment step can greatly reduce uncertainty in treatment assessment.
PMID- 17037131
TI - Coliforms and other microbial indicators occurrence in water and biofilm in full
scale distribution systems.
AB - Biofilm and microbial water quality were studied in four middle size full-scale
distribution systems (DS) in France serving 5,000-30,000 inhabitants (maximum
residence time 23-160h) through three sampling campaigns over 1 year. Three of
these DSs were chosen because of a quite high occurrence of bacterial indicators
(i.e. total coliforms), the last DS was considered as a reference. Biofilm was
studied on cast iron coupons incubated for more than 1 month in devices
continuously fed with water from the DS in conditions imitating those met in DS.
The devices were located at different points (4-6) along each DS. The abundance
of bacteria in biofilm was estimated by heterotrophic plate counts (HPC) after
detachment of the biofilm from the support by sonication. Microbiological water
quality was estimated in parallel; analysis of total coliforms, E. coli,
enterococci and anaerobic sulphide-reducing bacteria spores (ASRB spores) was
carried out in biofilm and water. Over the period of the study, 171 water samples
and 57 biofilm samples were collected. Over these 171 waters, 19 (11%) were
positive for at least one of the measured indicators while two biofilm samples
were positive (3.5%). Significant differences were observed in the levels of
contamination between the DSs. High residence time in the DS, low disinfectant
residual and high temperature increased the risk of indicator occurrence in the
water phase. Due to the low number of biofilm samples positive for bacterial
indicators, the data collected in the present study did not allow observation of
a direct association between biofilm and water contaminations, even if the
occurrence of indicators in water appeared on DSs with the highest density of
biofilm (HPC).
PMID- 17037132
TI - Effect of temperature and pipe material on biofilm formation and survival of
Escherichia coil in used drinking water pipes: a laboratory-based study.
AB - Segments of used drinking water pipes of galvanised steel (GS), cross-linked
polyethylene (PEX), copper pipes (Cu) or new medium-density polyethylene (PE)
were investigated for the formation of biofilm and survival of E. coli in biofilm
and in the water phase. Pipes were filled with water and incubated at 15 degrees
C or 35 degrees C under static conditions. Biofilm formation was followed during
32, 40 and 56 (58) d. The most dense biofilm was formed on GS, reaching
approximately 4.7 x 10(5) CFU/cm2 measured as heterotrophic plate count (HPC),
and at the other materials the density reached 3 x 10(3) CFU/cm2 on PE and PEX
and 5 x 10(1) and 5 x 10(2) CFU/cm2 on Cu pipes after 58d at 15 degrees C.
Biofilm HPC values were higher at 35 degrees C than at 15 degrees C, with only
slightly higher values on the metals, but 100-fold higher on PE and PEX.
Adenosine triphosphate (ATP) measurements confirmed the general trends observed
by HPC. Higher temperature was seen to be an important factor reducing E. coli
survival in the water phase in drinking water pipes. At 15 degrees C E. coli
survived more than 4 d in GS and Cu pipes and 8 d in PE pipes, but was not
detected after 48 h at 35 degrees C. The E. coli survived longer at both
temperatures in the glass control bottles than in the drinking water pipes.
Despite the obvious biofilm formation, E. coli was not detected in the biofilm at
any of the investigated surfaces.
PMID- 17037133
TI - Survival of Campylobacter jejuni in potable water biofilms: a comparative study
with different detection methods.
AB - Campylobacteria are important foodborne pathogens. C. jejuni bacteria have caused
several drinking water-related epidemics in Finland. Normally, C. jejuni is not
able to multiply in drinking water or in biofilms although it may survive in
biofilms. The survival of C. jejuni in biofilms was studied using the Propella
biofilm reactor. The number of bacteria was analysed with traditional culture
methods and with fluorescence in situ hybridisation (FISH). By culture methods C.
jejuni was detectable for only 1 d after spiking whereas bacteria were found from
biofilms for at least 1 week after spiking and from outlet water of the reactor
for 3 weeks when using FISH. These results suggested that C. jejuni may survive
in biofilms and culture methods probably seriously underestimate the real number
in water and in biofilms.
PMID- 17037134
TI - Modelling the length of microbiological protection zones around phreatic sandy
aquifers in The Netherlands.
AB - The aim of the current study was to calculate the size of protection zones around
(sub)oxic and anoxic sandy aquifers without confining layers using a virus
infection and transport model. The maximum allowable virus infection risk was 10(
4)/person/year at the 95% confidence level. Model results demonstrated that
phreatic (sub)oxic sandy aquifers in The Netherlands required protection areas
with a residence time of 43-117 d to ensure that the maximum virus infection risk
would not be exceeded. This was 0.7-2 x the current guideline of 60d. In
contrast, phreatic anoxic sandy aquifers without confining layers needed
protection zones of 555-898d to stay below the maximum virus infection risk, 9.5
15 x the current guideline. A sensitivity analysis of the model demonstrated that
the calculated protection zone was most sensitive for virus inactivation rate and
collision efficiency. Values of both parameters were predicted from values
obtained from previously published field and laboratory studies. At present, as
it is unknown if these values can also be used at other locations, model results
should be interpreted with care.
PMID- 17037135
TI - Using a weight-of-evidence approach for management of watersheds.
AB - This research used a weight-of-evidence approach to evaluate sources of
contaminants in a drinking water watershed that serves as part of the City of
Boston's water supply. The approach incorporated land use analysis using GIS,
sanitary surveys, traditional water quality monitoring and microbial source
tracking (MST) tools. Case-study tributaries were selected based on elevated
faecal coliform counts. Land use analysis and sanitary surveys were used to
identify suspected microbial sources, including residential septic systems,
agricultural animal operations, commercial/industrial operations and wildlife
activity. Sampling sites were selected to hydrologically isolate potential
contamination sources. Samples were collected seasonally over 1 year and analysed
for traditional and MST parameters. Results demonstrated that both septic systems
and a horse stable were contributing microbial loads in the first tributary. In
the second tributary, septic systems from the townhouses were contributing
microbial loads while a plant nursery was contributing organic matter. This
evidence was used to evaluate best management practices to mitigate the
contamination.
PMID- 17037136
TI - Membrane separation of indigenous noroviruses from sewage sludge and treated
wastewater.
AB - In this study, feasibility of membrane separation for the removal of indigenous
noroviruses (NVs) is evaluated. The indigenous NV gene was never detected from
ultrafiltration (UF) permeates of sewage sludge and treated wastewater.
Indigenous NV gene was also not detected from permeates of sewage sludge and
treated wastewater by microfiltration (MF) with a pore size of 0.1 microm
(MF0.1). Even though the pore size of MF (0.1 microm) was much larger than the
diameter of virus particle (approximately 30-40nm), more than 4-log10 reduction
value (LRV) at maximum was achieved by membrane separation with MF0.1. NV genes
were often detected from permeates of sewage sludge and treated wastewater by MF
with a pore size of 0.45 microm (MF0.45), although the maximum log10 reduction
values were more than 3.59 for sewage sludge and more than 2.90 for treated
wastewater. It is important to verify factors determining the removal efficiency
of viruses with MF membranes.
PMID- 17037137
TI - UV disinfection of wastewater effluents for unrestricted irrigation.
AB - Wastewater reuse in arid regions is important for the production of a water
resource to be utilised for non-potable purposes and to prevent the environmental
transmission of disease-causing agents. This study was conducted to evaluate the
effect of water quality on the comparative disinfection efficiency of viruses,
bacteria and spores by UV irradiation. Furthermore, the microbial quality of
effluent produced by coagulation, high rate filtration (HRF) and either UV
irradiation or chlorination was determined. Using low pressure collimated beam, a
UV dose of 80 mWs/cm2 was needed to achieve a 3-log10 inactivation of either
rotavirus SA-11 or coliphage MS2, whereas over 5-log10 inactivation of E. coli
was reached with a dose of only 20 mWs/cm2. B. subtilis inactivation was found to
be linear up to a dose of 40 mWs/cm2 and then a tailing up to a UV dose of 120
mWs/cm2 was observed. It is worth noting that effluent turbidity of < 5 NTU did
not influence the inactivation efficiency of UV irradiation. Operation of a pilot
plant to treat secondary effluent by coagulation, HRF and UV disinfection at a UV
dose of 80 mWs/cm2 resulted in the production of high quality effluent in
compliance with the Israel standards for unrestricted irrigation (< 10 CFU/100 mL
faecal coliform and turbidity of < 5 NTU). Sulphite reducing clostridia (SRC)
were found to be more resistant than coliphages and F coliform for UV
irradiation. The results of this study indicated that UV disinfection is suitable
for the production of effluents for unrestricted irrigation of food crops.
PMID- 17037138
TI - Evaluation of activated sludge treatment and the efficiency of the disinfection
of Giardia species cysts and Cryptosporidium oocysts by UV at a sludge treatment
plant in Campinas, south-east Brazil.
AB - Among many waterborne diseases the giardiasis and cryptosporidiosis are of
particular public health interest, because Giardia cysts and Cryptosporidium
oocysts can persist for long periods in the environment, and both pathogenic
protozoa have been implicated as the cause of many outbreaks of gastroenteritis
in the last 25 years. In order to evaluate the efficiency of cysts and oocysts'
removal by the activated sludge process, and by UV reactor in inactivating cysts
and oocysts in one wastewater treatment plant (WWTP) of Campinas, three sampling
points were selected for study: (1) influent, (2) treated effluent without UV
disinfection and (3) treated effluent with UV disinfection. Giardia spp. cysts
prevailed with higher density in the three different sample types.
Cryptosporidium spp. oocysts were observed in only two samples of influent and
just one sample of treated sewage with UV disinfection. In the animal infectivity
assay for Giardia spp, one mouse of the UV treated group revealed trophozoites in
intestinal scrapings. The results of the present study indicate that treatment by
activated sludge process delivered a reduction of 98.9% of cysts and 99.7% of
oocysts and UV disinfection was not completely efficient regarding the
inactivation of Giardia cysts in the case of the WWTP studied.
PMID- 17037139
TI - Impact of sewage treatment plants and combined sewer overflow basins on the
microbiological quality of surface water.
AB - In a small river catchment, microbiological quality of different sewage treatment
plants under regular conditions and in case of heavy rainfall, when combined
sewage overflow basins (CSOs) are activated, was examined regarding microbial
indicators and pathogens. In the watercourse, no self-cleaning effects could be
observed. Small compact treatment plants discharge treated wastewater with a poor
microbiological quality compared to river water quality and the quality of
treated wastewater of larger plants. During storm water events, concentrations of
microorganisms downstream of sewer overflows were approximately two logs higher
than during dry weather conditions. Concentrations of parasites decreased slowly
during the overflow, in parallel to filterable matter and particle-bound
substances. The annual load of microorganisms originating from CSOs significantly
exceeds the load from treated effluent of the sewage plants. Thus, an improved
hygienic quality of the water course could be achieved by preventing overflows
and by enhancing sewage treatment plants.
PMID- 17037140
TI - Bacteroides spp. as reliable marker of sewage contamination in Hawaii's
environmental waters using molecular techniques.
AB - Standard PCR (SPCR) and quantitative PCR (QPCR) assays using primers for general
and for human-specific Bacteroides 16S rRNA markers were selected as the
molecular tests to assess sewage contamination in recreational waters of Hawaii
and these same water samples were assayed for culturable concentrations of
selected faecal microbial indicators. The results of this study showed that the
general primer for Bacteroides was not useful because ambient and polluted water
samples were positive for this marker. However, use of human-specific primers
reliably detected sewage contamination. The human-specific Bacteroides detection
data supported previously reported conclusions that concentrations of alternative
faecal indicators (C. perfringens, FRNA coliphages) but not traditional faecal
indicators (faecal coliform, E. coli, enterococci) are reliable indicators of
faecal contamination in Hawaii's environmental waters. The QPCR assay for the
human-specific Bacteroides 16S rRNA marker was faster, more sensitive and more
reliable than comparable SPCR assay because OPCR assay provided additional
information such as melting temperatures, which confirmed that the right
amplicons were being measured and Ct values, which indicated the relative level
of faecal contamination.
PMID- 17037141
TI - Microbiological quality of reclaimed water used for golf courses' irrigation.
AB - Microbial quality of reclaimed water used for irrigation in two golf courses
located in the southern Iberian Peninsula (Spain and Portugal) was evaluated.
Bacterial indicators for faecal pollution (total and faecal coliforms,
Escherichia coli and enterococci) were tested by membrane filtration using
appropriate selective media. In addition, somatic E. coli bacteriophages, enteric
viruses (entero-, hepatitis A and rota-) and Legionella pneumophila were also
analysed. The results obtained showed that all wastewater treatment processes
reduced adequately the number of indicator microorganisms although a significant
correlation between pathogenic and indicator microorganisms tested was not found.
L. pneumophila was detected by PCR but not confirmed by culture. Survival
experiments of pathogenic microorganisms in aerosols and irrigated turf are
conducted to determine the health hazards for the golf practice and to propose a
microbial standard for wastewater used for irrigation of golf courses.
PMID- 17037142
TI - Quantification and genotyping of Cryptosporidium spp. in river water by quenching
probe PCR and denaturing gradient gel electrophoresis.
AB - A new detection method was developed for the simultaneous quantification and
genotyping of Cryptosporidium spp. in river water. Several modifications made to
the US EPA Method 1623 enabled high and stable recovery of Cryptosporidium from
40 L of river water (geometric mean = 35%, standard deviation = 8.7%). Quenching
probe PCR (QProbe PCR) was used to quantify the 18S rRNA gene of Cryptosporidium
spp. This method could successfully detect single oocysts in a sample, and the
lower quantitation limit was as low as 2.5 oocysts/sample. In addition,
denaturing gradient gel electrophoresis (DGGE) followed by DNA sequencing was
used to identify the genotypes. These methods were applied to detect
Cryptosporidium spp. in the Koyama River, Japan. The positive ratio was 69%
(11/16) with the maximum concentration of 59 oocysts/100 L. Seven genotypes
including two novel ones were identified. These results showed that this
detection method could provide valuable information on Cryptosporidium in river
water, both in the concentration and in the genotypes, which is essential for the
precise assessment of waterborne risk to human health.
PMID- 17037143
TI - Analysis of enterococci using portable testing equipment for developing countries
-variance of Azide NutriDisk medium under variable time and temperature.
AB - This report compares the enterococci count on samples obtained with Azide
NutriDisk (AND) (sterile, dehydrated culture medium) and Slanetz and Bartley (SB)
medium when exposed to a variable in incubation time and temperature. Three
experiments were performed to examine the recovery of enterococci on AND and SB
media using membrane filtration with respect to: (a) incubation time; (b)
incubation temperature; and (c) a combination of the two. Presumptive counts were
observed at 37, 41, 46 and 47 degrees C and at 20, 24, 28 and 48 h. These were
compared to AWWA standard method 9230 C (44 degrees C, 44 h). Samples were
confirmed using Kanamycin Aesculin Azide (KAA) agar. Friedman's ANOVA and
Students t-test analysis indicated higher enumeration of enterococci when grown
on AND (p = 0.45) than SB (p = < 0.001) at all temperatures with a survival
threshold at 47 degrees C. Significant results for AND medium were noted at 20 h
(p = 0.021), 24 h (p = 0.278) and 28 h (p = 0.543). The study concluded that the
accuracy of the AND medium at a greater time and temperature range provided
flexibility in incubator technology making it an appropriate alternative to SB
medium for monitoring drinking water using field testing kits in developing
countries.
PMID- 17037144
TI - Direct detection of bacterial faecal indicators in water samples using PCR.
AB - The presence of enteric pathogens in water resources represents a serious risk
for public health. Therefore, their precise detection, and especially detection
of E. coli, which is obviously regarded as the main indicator of faecal
contamination of water, is an essential step in ensuring bacterial safety of
water. Numerous PCR protocols for detection of E. coli have been published to
date. They are usually based on amplification of regions derived from lacZ (beta
D-galactosidase) and uidA (beta-D-glucuronidase) gene sequences. However, these
methods are not universal enough for precise detection of all E. coli strains
found in water samples. We developed a novel triplex PCR method for detection of
E. coli in which cyd gene coding for cytochrome bd complex was co-amplified along
with lacZ and uidA genes. Our triplex PCR approach significantly increases the
specificity and reliability of E. coli detection in water samples. This approach
allowed us to distinguish Shigella flexneri from E. coli. In addition, we were
able to detect even non-coliform Klebsiella and Raoutella spp., some of which can
also cause infections to humans.
PMID- 17037145
TI - Comparison of three different media for the detection of E. coli and coliforms in
water.
AB - The European Drinking Water Directive defines reference methods for the
enumeration of microbiological parameters in drinking water. The method to be
used for Escherichia coli and coliforms is the membrane filtration technique on
Lactose TTC agar with Tergitol 7. Many technical drawbacks of the procedure, as
well as its limitations regarding the recent taxonomy of coliforms, make it
necessary to evaluate alternative methods. Two alternative assays, a chromogenic
media (m-ColiBlu24) and a defined substrate technology-DST test (Colilert
18/Quanty Tray) were compared with the ISO standard with attention to the
phenotypic characteristic of the isolates. Results showed that the ISO method
failed to detect an important percentage of coliforms and E. coli while m
ColiBlu24 and Colilert 18 provided results in a shorter time allowing the
simultaneous detection of E. coli and coliforms with no further confirmation
steps.
PMID- 17037147
TI - The association of E. coli and soil particles in overland flow.
AB - The removal of E. coli from overland flow under saturation-excess runoff
conditions was investigated in experimental field plots that were 1 m wide and 5
m long. Variation in the attenuation of bacteria and distance transported was
quantified under contrasting flow conditions. In addition, the impact of soil
tillage upon microbial attenuation was examined by comparing results derived from
grassed plots (intact) with those subject to tillage with the soil left bare
(cultivated). For intact plots subjected to a flow of 2 L/min, 27% of the E. coli
in the flow was removed after 5 m with removal following a logarithmic function
with respect to distance. For the higher flow rates of 6 L/min and 20 L/min, no
attenuation trend was observed over this distance. E. coli removal during flow
across the cultivated plots was significantly greater compared to the intact
plots. This was attributed to a greater infiltration rate in the cultivated plots
(due to the tillage) which promoted a greater volume of flow to pass through the
soil matrix, providing the opportunity for filtration and adsorption of microbes.
Logarithmic trends with respect to distance were observed for all flow rates
tested on the cultivated plots (2, 6 and 20 L/min). Total removal after 5 m at a
flow rate of 2 L/min was 41% and again removal efficiency decreased as the flow
rate increased. Analysis of the transported state of the E. coli revealed that
the bacteria were being transported predominantly in particles less than 20
microm in diameter and were not attached to large (dense) soil particles. The
limited removal (< 50%) of bacteria from overland flow under saturation-excess
runoff conditions in these experiments appeared, therefore, to be primarily due
to a lack of settling or deposition. Instead, most bacteria remained entrained
within the overland flow down the length of the plots.
PMID- 17037146
TI - Culture of Helicobacter pylori from domestic water samples--the impact of strain
variation on growth on solid and in liquid media.
AB - Helicobacter pylori is an important global human pathogen and there is growing
evidence from PCR assays that contaminated drinking water might be a possible
source of infection in some circumstances. There are no validated protocols for
direct isolation but various culture media have been developed for possible
environmental sampling. Our aim here was to investigate how inter-strain
variation might affect the interpretation of results with such media. Two
laboratory adapted reference strains and four recent clinical isolates were
tested on four solid media and in ten liquid media. Considerable variation was
found between strains in their ability to recover on the different media after
stress exposure (suspension in sterile tap water). Generally, clinical isolates
were less robust than the laboratory-adapted strains and, overall, the former
required longer recovery times. Our findings highlighted the importance of using
a range of isolates for evaluations, as examination of laboratory-adapted strains
alone did not provide an accurate representation of the utility of media that may
be used to recover H. pylori from water.
PMID- 17037148
TI - Adsorption of viruses to soil: impact of anaerobic treatment.
AB - The adsorption of viruses in untreated flushed dairy manure wastewater (FDMW),
anaerobically digested flushed dairy manure wastewater (ADFDMW) and groundwater
to sandy soil was investigated. Batch adsorption studies showed differential
adsorption of viruses in groundwater to soil. Less than 75% of PRD1 and MS2 added
to groundwater adsorbed after 1 h, but greater than 95% of phiX174 and poliovirus
1 adsorbed to the soil. Adsorption differences in groundwater were related to the
isoelectric points of the viruses. Suspending phages in untreated and treated
wastewater reduced adsorption compared with groundwater. For MS2, more phages
were adsorbed using ADFDMW than with FDMW. Adsorption of poliovirus 1 was not
affected by FDMW and ADFDMW. Small column studies (6 x 2.5 cm) produced a similar
trend in that adsorption was observed with groundwater and both FDMW and ADFDMW
reduced virus adsorption. Groundwater, FDMW or ADFDMW did not affect the
adsorption of poliovirus 1 in column studies. The major difference between FDMW
and ADFDMW was in mobilisation of adsorbed viruses. The application of FDMW to
soil columns with adsorbed viruses caused significantly more viruses to be
mobilised than did the application of rainwater or ADFDMW. These results showed
that treating FDMW by anaerobic digestion increased the adsorption of viruses to
soil and decreased detachment of adsorbed viruses. As the potential for new
zoonotic pathogens becomes known, the treatment of animal wastes may become
mandatory. The assessment and management of viruses in manure for addressing
possible risk to animal and human health is of interest.
PMID- 17037149
TI - Comparative stability and growth requirements of S. aureus and faecal indicator
bacteria in seawater.
AB - The fate (stability, multiplication) of S. aureus, E. coli and E. faecalis was
determined in three classes of recreational waters (seawater, estuarine, stream)
supplemented with nutrients in the form of sewage and peptone. In the absence of
sunlight (24 +/- 2 degrees C), all bacteria in all water samples did not multiply
and were slowly (days) inactivated. When 50% sewage was added to all water
samples, E. coli and E. faecalis multiplied but S. aureus did not. When peptone
(0.05%, 0.5%) was the added nutrient, the three bacteria multiplied. In the
presence of sunlight (15-27 degrees C), S. aureus was inactivated rapidly (hours)
in all water samples. These results show that when their nutritional requirements
are met, S. aureus, E. coli and E. faecalis can multiply in the high salinity
conditions of seawater. However, under environmental conditions, sunlight is an
effective natural bactericidal agent.
PMID- 17037150
TI - Modelling faecal coliforms dynamics in the Seine estuary, France.
AB - A model describing the dynamics of faecal coliforms (FC) in the Seine estuary has
been developed and coupled with a three-dimensional hydrodynamic model. As input
to this model three types of FC sources were considered: (1) FC transported by
the Seine river flow at the estuary entrance at Poses dam; (2) FC brought in
through the tributaries of the Seine estuary; and (3) the outfalls of the treated
effluents of the WWTPs located along the estuary. As previous studies in the
Seine estuary showed that a large proportion of FC was attached to SM, two pools
of FC were considered separately in the model: free FC and FC attached to SM. Two
main processes controlling the fate of FC in the estuary were considered:
mortality and settling. The model calculates for a given discharge of the Seine
river at Poses the longitudinal distribution of FC along the estuary. The model
was validated by comparison of model calculations with experimental data in
various hydrological conditions. The model also correctly reproduced the impact
of the main river flow rate on the level of estuarine water's contamination.
Finally, the model was used to test different scenarios of sanitation, suggesting
priorities for sanitation efforts.
PMID- 17037151
TI - Comparison of total and faecal coliforms as faecal indicator in eutrophicated
surface water.
AB - The aim of this study was to evaluate the use of total coliforms (TC) and faecal
coliforms (FC) using a membrane filtration method for precise monitoring of
faecal pollution in Korean surface water. The samples were collected in Korea
from both main rivers and their tributaries. Presumptive TC * FC were enumerated.
The ratios of presumptive FC to TC were not constant, but varied widely, and TC
were difficult to enumerate because of overgrowth by background colonies. For FC
this was not the case. Seven hundred and three purified strains of presumptive TC
* FC and their background colonies were biotyped using API 20E. Among 272
presumptive TC, non-faecal related species, Aeromonas hydrophila dominated
(34.6%) and E. coli accounted for only 5.1%. In contrast, E. coli made up 89% of
the 209 presumptive FC. Furthermore, of 164 background colonies on Endo Agar LES,
54.9% was A. hydrophila, while background colonies on m-FC Agar were few (58
strains), and despite their atypical colony appearance, most of them were
biotyped as enteric bacteria. These results reveal that the detection of FC
rather than TC using m-FC Agar is more appropriate for faecal pollution
monitoring in eutrophicated surface water located in a temperate region.
PMID- 17037152
TI - One-year monthly monitoring of Torque teno virus (TTV) in river water in Italy.
AB - Torque teno virus (TTV) is prevalent worldwide in general populations but at
present is not related with any specific pathology. Its presence in faeces and
its remarkable environmental stability suggest the possibility of using it as an
indicator of faecal contamination in the environment. To evaluate the waterborne
spread of TTV and its possible relationship with human pathogen enteric viruses,
water samples were collected monthly for a year (May 2004-April 2005) from a
river receiving the effluent of the treatment plant of the city of Pisa,
concentrated and assayed with bimolecular tests (PCR, RT-PCR). TTV was detected
in three samples (25%) while 16% of samples were positive for enteroviruses, 33%
for rotaviruses, 8% for noroviruses genotype 1 and 25% for noroviruses genotype
2. Only two TTV samples (June and January) were also positive for rotavirus and
norovirus, respectively. The detection of TTV in water confirmed its possible
faecal-oral route of transmission but data are still insufficient to draw
conclusions about the role of TTV as a viral indicator.
PMID- 17037153
TI - Genotyping of single Cryptosporidium oocysts isolated from sewage and river
water.
AB - The study was designed to genotype individual Cryptosporidium oocysts using an
18S rRNA gene-based semi-nested PCR and direct sequencing procedure. Positive PCR
amplification was observed in all single C. parvum HNJ-1 oocyst samples tested.
Semi-nested PCR and direct sequencing was applied to Cryptosporidium oocysts
isolated from sewage and river water. The procedure could genotype 54% of FITC
stained single oocysts isolated from sewage and 32% from river water. The
predominant genotype in both sewage and river water was C. parvum genotype 1,
accounting for 33 and 25%, respectively, of all the FITC-stained intact
Cryptosporidium oocysts present.
PMID- 17037154
TI - Monitoring of human enteric viruses and coliform bacteria in waters after urban
flood in Jakarta, Indonesia.
AB - Floodwaters in Kampung Melayu village, Jakarta, Indonesia, as well as river water
and consumable water (including groundwater and tap water) samples in flooded and
non-flooded areas, were quantitatively analysed to assess occurrence of viruses
and total coliforms and E. coli as bacterial indicators after flooding event.
High numbers of enterovirus, hepatitis A virus, norovirus (G1, G2) and adenovirus
were detected at high concentration in floodwaters and waters sampled from
Ciliwung River which runs across metropolitan Jakarta and is used widely for
agriculture and domestic purposes by poor residents. One out of three groundwater
wells in the flooded area was contaminated with all viruses tested while no
viruses were found in groundwater samples in non-flooded areas and tap water
samples. The results revealed that human enteric viruses, especially hepatitis A
virus and adenovirus, were prevalent in Jakarta, Indonesia. This study suggested
that flooding posed a higher risk of viral infection to the people through
contamination of drinking water sources or direct contact with floodwaters.
PMID- 17037155
TI - Detection and occurrence of antimicrobially resistant E. coli in groundwater on
or near swine farms in eastern North Carolina.
AB - The use of antibiotics for growth promotion and disease treatment by the
commercial swine industry has led to high proportions of multiple antibiotic
resistant enteric bacteria being shed by these animals and concerns about the
environmental spread of these bacteria. A study was conducted to quantify the
extent of release of antibiotic-resistant E. coli from swine farms into
groundwater. Four study sites, two swine farms and two reference sites (crop
farms), with known groundwater flow paths were screened for E. coli four times
over the course of one and a half years. A total of 100 biochemically-confirmed
E. coli were collected from the four sites. There were statistically
significantly higher E. coli levels at the two swine farm sites than at the
reference sites. The bacterial isolates were tested for antibiotic resistance
using a panel of 17 drugs that are typical of human and veterinary use. There
were 19 and 71 E. coli isolates from swine farms #1 and #2, respectively, with
most (68%) being resistant to 1 -6 antimicrobials. Only one E. coli isolate from
each of the reference sites showed antimicrobial resistance traits. The results
of this study demonstrate that antibiotic-resistant E. coli strains are present
in groundwaters of swine farms with a typical lagoon and land application system
for waste management.
PMID- 17037156
TI - Hybridisation of F+ RNA coliphages detected in shellfish samples with
oligonucleotide probes to assess the origin of microbiological pollution of
shellfish.
AB - Current measures for controlling the public health risks associated with bivalve
molluscan shellfish consumption rely on the use of Escherichia coli to indicate
the sanitary quality of shellfish harvesting areas. However, it has been
demonstrated that E. coli is an inadequate indicator of the viral risk associated
with shellfish. An alternative indicator, male-specific B+ coliphages, have been
investigated as viral indicators of faecal contamination that may provide source
specific information for impacted environmental waters. This study compared the
distribution of E. coli and F+ RNA bacteriophages in shellfish grown in
harvesting areas of Greece and also examined the presence and proportions of the
different subgroups of F+ RNA coliphages in shellfish. F+ RNA bacteriophages were
present in shellfish at higher concentrations than E. coli. Elevated numbers of
F+ RNA bacteriophages observed in the winter concur with the known increased
viral risk associated with shellfish harvested at that time of year in Greece.
The majority of F+ RNA coliphages detected in shellfish samples belonged to group
IV which indicated the possible presence of animal faecal material in sample
harvesting areas. Phages of groups II and III (human waste and human faecal
material, respectively) were present at low levels. Finally, 8% of the phages
hybridised were found to belong to group I. The presence of group IV showed
seasonal distribution (more in winter, less in summer) whereas the other groups
did not show any difference. Monitoring of F+ coliphage subgroups may indicate
the presence and major sources of microbial inputs to surface waters; however,
environmental effects on the relative occurrence of different groups need to be
considered.
PMID- 17037157
TI - Effects of rainfall on the occurrence of human adenoviruses, total coliforms, and
Escherichia coli in seawater.
AB - A two-month survey was conducted in order to evaluate the effects of rainfall on
the fate of microorganisms in seawater in the Tokyo Bay, Japan. The seawater
sample (1,000 mL) was applied to a method to concentrate virus, followed by a
quantification of human adenoviruses using the real-time PCR. Total coliforms and
E. coli, which were determined by the colony forming method, were detected in all
47 seawater samples, while human adenoviruses were detected in 38 (81%) of the
samples. The concentration of tested microorganisms showed 1-2 log units increase
after rainfall events, followed by the gradual decrease to the level before the
rainfall within a few days.
PMID- 17037158
TI - Endemic Cryptosporidium infection and drinking water source: a systematic review
and meta-analyses.
AB - Cryptosporidium is a well-known cause of diarrhoea in humans. Little is known
about risk factors associated with endemic cryptosporidiosis, which constitutes
the majority of cases. We carried out meta-analyses to verify if drinking water
is also associated with endemic infection and to assess the magnitude of the
associations. The global meta-analysis suggests that there is an increased risk
of Cryptosporidium infection among unsafe water users (OR 1.40 [1.15, 1.72]).
Studies were stratified, according to the exposure to different sources of safe
drinking water, due to the heterogeneity presented. The consumption of non-well
and unboiled water was associated with an increased chance of endemic
cryptosporidiosis, though only the latter was significant (OR 1.45 [0.95, 2.20];
OR 1.61 [1.09, 2.38]). Drinking non-bottled water did not present a risk factor
associated with endemic cryptosporidiosis (OR 0.87 [0.72, 1.05]). These meta
analyses present results that could be useful to clarify the epidemiology of
Cryptosporidium. We recommend that other risk factors could also be studied by
this approach.
PMID- 17037159
TI - Epidemiological surveillance of human enteric viruses by monitoring of different
environmental matrices.
AB - In the aim of studying possible relations between viruses detected in clinical
specimens and the ones found in different environmental matrices, in the period
May 2004 to April 2005, the collection of faecal samples from gastroenteritis
cases and the monthly monitoring of raw and treated wastewater, river water,
seawater and mussels were carried out. The viruses considered for environmental
monitoring were adenovirus, rotavirus, enterovirus, norovirus, hepatitis A virus
(HAV) and Torque teno virus (TTV): they were searched for with PCR and RT-PCR and
confirmed by gene sequencing. Faecal coliforms and somatic coliphages' counts
were also determined. The surveillance of case detected 45 positive faecal
samples out of 255 (17.6%) while 35 of 56 environmental samples (62.5%) resulted
positive for at least one of the considered viruses. The detection of the same
viral strain in the faeces of gastroenteritis cases and in water was possible for
adenovirus and rotavirus, which were also predominant in environmental matrices;
thus they could be considered as a reference for risk assessment.
PMID- 17037160
TI - Microbial exposure assessment of an urban recreational lake: a case study of the
application of new risk-based guidelines.
AB - New WHO and Australian guidelines promote a risk-management approach for
minimising exposure to pathogens in recreational waters. Between 2003 and 2005,
they were applied to Lake Parramatta (10 ha, 450 ML), a potential recreation site
in Sydney, Australia. A three stage approach was developed involving (1) initial
suitability assessment using historic data, (2) revised suitability assessment
based on new data and (3) characterisation of hazardous (especially wet weather)
events. Contrary to the stage 1 suitability classification, stage 2 baseline data
indicated that during dry weather the lake had water quality sufficient for
primary contact recreation (95th percentiles for enterococci = 19 MPN/100, n =
50) and the major pathogen source was wildfowl. Guideline principles provided a
rationale for collecting microbiological and geographic data needed to understand
local cycles of lake contamination/recovery. The concept of hazardous events was
particularly useful. Studies of stormwater events led us to identify a transition
point (> 10 mm rainfall in 24 h) where human-faecal pathogen risks increased and
access needed to be controlled. Together baseline and event data yielded
operational tools (i.e. event detection methods, action triggers, auditing
criteria, remediation priorities) for minimising bather exposure.
PMID- 17037161
TI - Microbial risk and removal--a utility perspective.
AB - In this paper the results of a sampling programme, undertaken as part of the EU
MicroRisk project, are described. This project was undertaken to ascertain the
occurrence of pathogens and indicators in the River Thames and their subsequent
removal through a treatment works. Appropriate physico-chemical surrogates, as
determined by statistical correlation are proposed for the microorganisms
identified in the raw water. This study shows that under normal raw water
conditions the treatment works is able to remove microbial contamination with a
significant margin of safety.
PMID- 17037162
TI - Pathogen monitoring offers questionable protection against drinking-water risks:
a QMRA (quantitative microbial risk analysis) approach to assess management
strategies.
AB - Risk mitigation provided by human monitoring and control over a water supply
system has been consistently overlooked when estimating pathogen exposure to
consumers. The Systems-Actions-Management (SAM) framework lends itself neatly to
Quantitative Microbial Risk Assessment (QMRA) as one way to establish this link.
The general premise is that an organisational protocol will influence how a human
controller behaves, in turn influencing the system performance. For illustrative
purposes, the framework was applied to a hypothetical water supply system to
quantify the risk reduction offered by routine Cryptosporidium monitoring and the
response to oocyst 'detects'. Our findings suggest that infrequent direct
pathogen monitoring may provide a negligible risk barrier. The practice of
sampling treated water to verify microbiological integrity is also dubious:
oocyst densities were largely under-estimated, in part due to the spatial
dispersion of oocysts in the waterbody, but predominantly from imperfect
detection methods. The development of 'event-driven' monitoring schemes with
barrier performance-based treatment verification methods, as promoted in new
guidelines, is supported as a pressing issue to reduce the likelihood of
undetected pathogen passage through a treatment plant.
PMID- 17037163
TI - Microbial risk assessment of dental unit water systems in general dental practice
in Greece.
AB - Water was sampled from source water, the 3-in-1 syringe and the air rotor water
line of dental unit water systems (DUWS) in general dental practice in Attica,
Greece. A section of the water line supplying the 3-in-1 syringe was cut for
biofilm analysis. High total viable counts, Mycobacterium spp. and Pseudomonas
aeruginosa were detected in the samples. Back siphonage was evidenced by the
presence of blood and the recovery of oral anaerobes from the samples. Legionella
pneumophila was recovered from 16.1% of biofilm samples. All tested disinfectants
reduced the total viable counts of the DUWS to < 100 CFU/mL.
PMID- 17037164
TI - A review of ADM1 extensions, applications, and analysis: 2002-2005.
AB - Since publication of the Scientific and Technical Report (STR) describing the
ADM1, the model has been extensively used, and analysed in both academic and
practical applications. Adoption of the ADM1 in popular systems analysis tools
such as the new wastewater benchmark (BSM2), and its use as a virtual industrial
system can stimulate modelling of anaerobic processes by researchers and
practitioners outside the core expertise of anaerobic processes. It has been used
as a default structural element that allows researchers to concentrate on new
extensions such as sulfate reduction, and new applications such as distributed
parameter modelling of biofilms. The key limitations for anaerobic modelling
originally identified in the STR were: (i) regulation of products from glucose
fermentation, (ii) parameter values, and variability, and (iii) specific
extensions. Parameter analysis has been widespread, and some detailed extensions
have been developed (e.g., sulfate reduction). A verified extension that
describes regulation of products from glucose fermentation is still limited,
though there are promising fundamental approaches. This is a critical issue,
given the current interest in renewable hydrogen production from carbohydrate
type waste. Critical analysis of the model has mainly focused on model structure
reduction, hydrogen inhibition functions, and the default parameter set
recommended in the STR. This default parameter set has largely been verified as a
reasonable compromise, especially for wastewater sludge digestion. One criticism
of note is that the ADM1 stoichiometry focuses on catabolism rather than
anabolism. This means that inorganic carbon can be used unrealistically as a
carbon source during some anabolic reactions. Advances and novel applications
have also been made in the present issue, which focuses on the ADM1. These papers
also explore a number of novel areas not originally envisaged in this review.
PMID- 17037165
TI - Implementing ADM1 for plant-wide benchmark simulations in Matlab/Simulink.
AB - The IWA Anaerobic Digestion Model No.1 (ADM1) was presented in 2002 and is
expected to represent the state-of-the-art model within this field in the future.
Due to its complexity the implementation of the model is not a simple task and
several computational aspects need to be considered, in particular if the ADM1 is
to be included in dynamic simulations of plant-wide or even integrated systems.
In this paper, the experiences gained from a Matlab/Simulink implementation of
ADM1 into the extended COST/IWA Benchmark Simulation Model (BSM2) are presented.
Aspects related to system stiffness, model interfacing with the ASM family, mass
balances, acid-base equilibrium and algebraic solvers for pH and other
troublesome state variables, numerical solvers and simulation time are discussed.
The main conclusion is that if implemented properly, the ADM1 will also produce
high-quality results in dynamic plant-wide simulations including noise, discrete
sub-systems, etc. without imposing any major restrictions due to extensive
computational efforts.
PMID- 17037166
TI - Activity corrections for ionization constants in defined media.
AB - Correcting ionization constants for activity effects can have a larger impact on
some ionic species than correcting for temperature effects. Computer trials
compared two pH calculation methods, and showed that an interpolation algorithm
found a precise charge balance quickly but was unstable under certain conditions,
while a slower pH search method was stable under all test conditions. The optimal
calculation strategy was a hybrid of these two approaches. The hybrid calculation
method is stable, quick, includes activity and temperature corrections, does not
need kinetic rate constants, allows all known ionic species to be included, and
allows for easy addition of new chemical species.
PMID- 17037167
TI - Identifiability study of the proteins degradation model, based on ADM1, using
simultaneous batch experiments.
AB - The objective of the present study is to analyse kinetic and stoichiometric
parameter values of gelatine anaerobic degradation at thermophilic range, based
on an experiment designed to elucidate if volatile fatty acids (VFA) are
inhibitors of the hydrolysis process. Results showed that VFA are not inhibiting
the hydrolysis process. The ADM1 model adequately expressed the consecutive steps
of hydrolysis and acidogenesis, with estimated kinetic values corresponding to a
fast acidogenesis and slower hydrolysis. The hydrolysis was found to be the rate
limiting step of anaerobic degradation. Estimation of yield coefficients based on
the relative initial slopes of VFA profiles obtained in a simple batch experiment
produced satisfactory results. From the identification study, it was concluded
that it is possible to determine univocally the related kinetic parameter values
for protein degradation if the evolution of amino acids is measured in
simultaneous batch experiments, with different initial protein and amino acids
concentrations.
PMID- 17037168
TI - An extension of the Anaerobic Digestion Model No. 1 to include the effect of
nitrate reduction processes.
AB - Nitrate reduction processes were incorporated into the IWA Anaerobic Digestion
Model No. 1 (ADM1) in order to account for the effect of such processes on
fermentation and methanogenesis. The general structure of the ADM1 was not
changed except for modifications related to disintegration and hydrolysis of
complex organic matter and decayed biomass. A fraction of butyrate/valerate and
propionate degraders was assumed to be the fermentative denitrifiers carrying out
fermentation in the absence of N-oxides. Nitrate reduction proceeded in a
stepwise manner to nitrite, nitric oxide, nitrous oxide and nitrogen gas using
four substrates as electron and/or carbon source. The utilization of the four
substrates and N-oxides was based on stoichiometry and kinetics. The inhibitory
effect of N-oxides on the methanogens was accounted for by the use of non
competitive inhibition functions. Model simulations were compared with
experimental data obtained with a batch, mixed fermenting and methanogenic
culture amended with various initial nitrate concentrations.
PMID- 17037169
TI - Critical analysis of some concepts proposed in ADM1.
AB - The Anaerobic Digestion Model No. 1 (ADM1) has been developed by the expert task
group of the IWA to establish a common platform for simulation of a wide variety
of anaerobic degradation processes. It enables comparison of different methods
and parameter values for description of specific sub-processes, with the methods
and default values proposed by the task group. This will hopefully stimulate a
more structured discussion on anaerobic digestion modelling compared to the
recent past, when many different researchers developed a slightly different model
and it remained largely unclear what could, and what could not be compared. In
this paper we take the liberty to criticize some aspects of ADM1 and its
implementation, as we think they represent concepts that are too easily
extrapolated from activated sludge models. The specific subjects discussed here
are the COD-based description of the reaction stoichiometry (i), the widely
adopted use of a constant value for the solid retention time high-rate anaerobic
bioreactors (ii), and the kinetic description of the acetogenic reactions as
proposed in ADM1 (iii).
PMID- 17037170
TI - Use of the ADM1 to investigate the effects of acetoclastic methanogen population
dynamics on mesophilic digester stability.
AB - The ADM1 was employed to assess the effect of variations in solids hydrolysis and
acetoclastic methanogen process characterizations on municipal digester stability
relating to excess acetate utilization capacity. First-order single- and dual
pathway hydrolysis rate functions and single and competitive acetoclastic
methanogen rate functions were implemented in the ADM1. The acetate capacity
number (ACN), defined as the ratio between the maximum acetate utilization rate
and the average acetate production rate, was used to index digester instability.
Simulations of a single CSTR at steady state indicate a similar ACN can be
obtained with a 12-day SRT digester dominated by Methanosarcina sp and a 24-day
SRT digester dominated by Methanosaeta sp. An increase in ACN with a decrease in
SRT representing Methanosarcina sp. selection was observed for particulate feed
loadings from 40 g COD/L to 90 g COD/L. Feeding frequency and dual-pathway
hydrolysis were found to have less effect on the ACN than the competitive
acetoclastic model structure.
PMID- 17037171
TI - Description of nitrogen incorporation and release in ADM1.
AB - ADM1 represents a universally applicable biokinetic model for the mathematical
description of anaerobic digestion of different types of organic substrates.
Digestion of particulate composites is described as a five-stage process
involving disintegration, hydrolysis, acidogenesis, acetogenesis and
methanogenesis, of which the last three process steps are represented by growth
kinetics of the specific degrading biomass. Decay of the produced biomass
according to ADM1 is depicted by a recycle mass flux to the composite particulate
substrate. Consequently two different actions are lumped into one process
describing both conversion of feed substrate (depending primarily on influent
characterisation) and generation of decay products (depending on digestion
performance). In this presentation the introduction of a separate compound of
inert decay products in analogy to ASM1 is suggested. Model calibration of
separately monitored digestion of primary and secondary sludge (nitrogen content
0.030 g N/g TSS and 0.051 g N/g TSS, respectively) reveals the advantage of a
clear distinction of disintegration and decay. The fate of nitrogen in the course
of incorporation and release (0.016 g N/g TSS compared to 0.028 g N/g TSS) during
digestion processes is comprehensible and the final ammonia concentration in the
rejection water becomes predictable.
PMID- 17037172
TI - Applications and limitations of ADM 1 in municipal wastewater solids treatment.
AB - The ADM 1 model has been implemented in a steady-state whole wastewater plant
simulator. The ADM 1 model has been in use with good success for approximately 2
years on a wide range of wastewater treatment facilities. However, a number of
modifications were necessary to allow it to be used in the context of municipal
wastewater treatment. It was found that the model's use was greatly simplified if
used in conjunction with a larger plant simulator to assist in the feed
fractionation. It was also found that a better fit to actual operating data was
achieved if some of the slowly biodegradable particulate fraction was partitioned
into ADM particulate fractions other than the composite fraction. Another
significant limitation of the model is in the absence of phosphorus modeling. The
ADM model needs to have phosphorus handling for all the relevant fractions, and
needs to include the handling of inorganic reactions such as struvite
precipitation and metal phosphate/metal hydroxide precipitation. Activity effects
on chemical equilibria are significant when considering phosphorus. Also of
importance in wastewater treatment is the fate of sulfur compounds. This includes
the generation of H2S in the digester gas and the fate of the sulfur species in
the digested sludge (as a predictor of odour-generating potential).
PMID- 17037173
TI - An approach for substrate mapping between ASM and ADM1 for sludge digestion.
AB - Kinetic modelling of the hydrolysis stage of municipal activated sludge, which is
presumed to be the rate-limiting step in the anaerobic sludge digestion process,
was studied by measuring methane production rate (MPR) in anaerobic batch tests.
The MPR curves revealed that the degradable organic components in municipal
sludge could be classified into two fractions having different kinetics. The
first fraction (XS1) constituted about 55% of the sludge COD and degraded with
first-order kinetics. The second fraction (XS2), which degraded during the
initial phase, accounted for about 21% of sludge COD. The degradation kinetics
for XS2 was expressed by Contois-type equation with respect to concentration of
substrate in the fed sludge and that of active biomass in the mixture.
Simultaneous batch aerobic respirometric tests showed that the activated sludge
was composed of 53% heterotrophic biomass (XH-Aerobe) COD and 20% of slowly
biodegradable COD (XS), that had same kinetic expressions as observed in the
batch anaerobic tests. The observed correlation between substrate fractions
suggests XS1 and XS2 could be directly mapped to the aerobic state variables of
XH-Aerobe and Xs respectively. The degradation of XS1 seems to be anaerobic decay
of XH-Aerobe while XS2 is thought to be hydrolysis of XS by microcosm of the
sludge.
PMID- 17037174
TI - ADM1 application for tuning and performance analysis of a multi-model observer
based estimator.
AB - Anaerobic digestion model no.1 (ADM1) was used for tuning and performance
analysis of the multi-model observer based estimator (mmOBE). The mmOBE was based
on the variable structure model (VSM) of the anaerobic digestion model, which
consists of several local submodels, each of which describes a typical process
state. Depending on the hydraulic retention time, ADM1 simulated the
methanogenic, organic overload, and acidogenic states of the process. These
simulations allowed for optimising tunable parameters of the mmOBE. Owing to
relatively slow process dynamics, a data acquisition interval as large as one day
was sufficient to obtain acceptable accuracy. The simulations of mmOBE
performance showed excellent rate of mmOBE convergence to ADM1 outputs. Moreover,
mmOBE successfully estimated key kinetic parameters, such as maximal
transformation rates of CODs, VFAs, and methane. These estimations can be used in
the development of the advanced knowledge-based process system, which uses both
available measurements and estimations of key kinetic parameters for extended
diagnosis of failures and process trend analysis.
PMID- 17037176
TI - Modifying ADM1 to include formation and emission of odourants.
AB - A mathematical model that is based upon the ADM1 structure has been developed to
describe the formation and emission of odourous compounds in anaerobic sludge
digestion. Special emphasis is given to the general mechanisms for the formation
of common odorous sulfur compounds that are found in anaerobic digesters: methyl
mercaptan, dimethyl sulfide and hydrogen sulfide, as well as volatile fatty acids
and ammonia. The model includes multiple-reaction stoichiometry, microbial growth
kinetics and conventional material balances for an ideally mixed reactor.
Simulations that were performed with the model revealed that changes in common
operational parameters such as temperature, HRT and sludge metal content can
dramatically impact upon the gas phase concentrations of odourants. Additional
research is required to reduce uncertainty in the model formulation.
PMID- 17037175
TI - Variable stoichiometry with thermodynamic control in ADM1.
AB - The effect of a variable stoichiometry of the carbohydrate fermentation process
in the IWA Anaerobic Digestion Model No.1 (ADM1) is investigated. Most existing
anaerobic digestion models including ADM1 consider a fixed-stoichiometry for
their conversion processes. The ADM1 model was first transformed into an only mol
based model to remove some errors derived from the mixed COD-mol based standard
model and to allow for implementation of the variable stoichiometry.
Consequently, the values of the butyrate and acetate catabolic yields of
carbohydrate fermentation are made dependent on the hydrogen concentration and
the reactor pH according to the predictions of a recently developed mixed culture
fermentation model based on thermodynamic considerations. The simulation results
obtained showed no significantly different responses in terms of effluent quality
and system robustness between the standard and the variable stoichiometry ADM1
under overload conditions, and for both single- and two-step anaerobic digestion
configurations. This behaviour is explained by the non-limiting acetogenic
activity that compensated for the changes in the acidogenic products, typical
behaviour for serial processes close to equilibrium. Based on the results
obtained, thermodynamic rather than kinetic control for these conversions is
suggested. Depending on the objectives to be met, lumping of carbohydrate
fermenters and oxidative acetogens into a single biomass group with a variable
stoichiometry is proposed for further consideration.
PMID- 17037177
TI - Simulation of DEHP biodegradation and sorption during the anaerobic digestion of
secondary sludge.
AB - Di-ethylhexyl phthalate (DEHP) has commonly been found in the sludge of municipal
wastewater treatment plants especially during anaerobic processing. It is slowly
biodegradable under anaerobic conditions. Due to its high hydrophobicity,
sorption-desorption processes can be rate-limiting for the compound
biodegradation. In this study, the anaerobic biodegradation of DEHP was
investigated through batch kinetic experiments and dynamic transitions of a
continuous stirred tank reactor (CSTR) fed with secondary sludge contaminated
with DEHP. A widely accepted model (ADM1) was used to fit the anaerobic digestion
of secondary sludge and was properly extended to account for DEHP removal, in
which mass transfer processes are also involved. It was shown that DEHP removal
was limited by the transfer of DEHP within the solid fraction. The criterion
selected for the distinction of the two sites was whether the compound sorbed in
those sites was bioavailable for biodegradation or not. Thus, the aqueous phase
and the surface of the biosolids were considered as suitable sites for the
compound to be bioavailable and the main bulk of the solid matrix was regarded as
sites, where the compound remains "protected" against biodegradation. The model,
fitted to the batch experimental data, was able to predict DEHP removal in the
CSTR operated at various HRTs.
PMID- 17037178
TI - Modelling anaerobic digestion acclimatisation to a biodegradable toxicant:
application to cyanide.
AB - The observed acclimatisation to biodegradable toxicants in anaerobic cassava
wastewater treatment is explained by modelling anaerobic cyanide degradation. A
complete degradation pathway is proposed for cyanide. Cyanide degradation is
modelled as enzymatic hydrolysis to formate and ammonia. Ammonia is added to the
inorganic nitrogen content of the digester while formate is degraded by the
hydrogenotrophic methanogens. Cyanide irreversible enzyme inhibition is modelled
as an inhibition factor to acetate uptake processes. Cyanide irreversible
toxicity is modelled as a decay factor to the acetate degraders. Cyanide as well
as added phosphorus buffer solution were considered in the chemical equilibrium
calculations of pH. The observed reversible effect after acclimatisation of
sludge is modelled by a population shift between two aceticlastic methanogens
that have different tolerance to cyanide toxicity. The proposed pathway is added
to the IWA Anaerobic Digestion Model no.1 (ADM1). The ADM1 model with the
designed extension is validated by an experiment using three lab-scale upflow
anaerobic sludge bed reactors which were exposed to different cyanide loadings.
PMID- 17037179
TI - Parameter analysis of the IWA Anaerobic Digestion Model No. 1 for the anaerobic
digestion of blackwater with kitchen refuse.
AB - The IWA anaerobic digestion model No.1 (ADM1) had been successfully applied to
the lab-scale mesophilic blackwater anaerobic digestion (BWAD) plant for cases of
only blackwater (BW) feeding and of BW plus kitchen refuse (KR) feeding. In this
paper, the simulation results of BW + KR anaerobic digestion are presented and
discussed, followed by the analyses and discussion of the critical and important
parameters as well as the performance of ADM1 based on these results. The raw BW
can contain up to 30% short chain fatty acids (SCFA) which severely impact the
performance of the model. The model proved that the disintegration/hydrolysis
rate of BW is around 4.5 d(-1), which is about ten times higher than that of KR
(Kdis,KR = 0.5 d(-1)). ADM1 is not sensitive to the distribution ratio among
carbohydrates, proteins and lipids. For BWAD the C4 metabolism can be integrated
in the uptake of LCFA. The uptake delay phenomenon was observed and cannot be
simulated by ADM1, but it is tolerable. No unique KI,NH3,ac is found out for all
investigated ammonia concentration ranges. Meanwhile, ADM1 is not sensitive to
KLa and kp1 so they can easily be set up.
PMID- 17037180
TI - Application of ADM1 for the simulation of anaerobic digestion of olive pulp under
mesophilic and thermophilic conditions.
AB - The management of the wastewater originating from olive oil producing industries
poses a serious environmental problem. Recently, two-phase production of olive
oil has been developed, leading to almost complete elimination of the bulk of the
generated wastewater and, is thus regarded as an environmentally friendly
technology. However, the main waste stream (olive pulp) is a slurry material
characterized by high solids concentration (approximately 30%), requiring
stabilisation before its final disposal. The anaerobic digestion of olive pulp is
studied in this work under mesophilic and thermophilic conditions in CSTR-type
digesters. The digesters were fed with water-diluted (1:4) olive pulp at an HRT
of 20 days and an OLR of 3.94 kg COD m(-3) d(-1). In order to study the process
kinetics, the digesters were subjected to impulse disturbances of different
substrates. The IWA anaerobic digestion model was used to simulate the reactors'
response. Some key process parameters, such as the specific maximum uptake rate
constants and the saturation constants for the volatile fatty acids degradation
were estimated and compared with the standard values suggested by the ADM1.
PMID- 17037181
TI - ADM1-based methodology for the characterisation of the influent sludge in
anaerobic reactors.
AB - This paper presents a systematic methodology to characterise the influent sludge
in terms of the ADM1 components from the experimental measurements traditionally
used in wastewater engineering. For this purpose, a complete characterisation of
the model components in their elemental mass fractions and charge has been used,
making a rigorous mass balance for all the process transformations and enabling
the future connection with other unit-process models. It also makes possible the
application of mathematical algorithms for the optimal characterisation of
several components poorly defined in the ADM1 report. Additionally, decay and
disintegration have been necessarily uncoupled so that the decay proceeds
directly to hydrolysis instead of producing intermediate composites. The proposed
methodology has been applied to the particular experimental work of a pilot-scale
CSTR treating real sewage sludge, a mixture of primary and secondary sludge. The
results obtained have shown a good characterisation of the influent reflected in
good model predictions. However, its limitations for an appropriate prediction of
alkalinity and carbon percentages in biogas suggest the convenience of including
the elemental characterisation of the process in terms of carbon in the
analytical program.
PMID- 17037182
TI - Waste characterization for implementation in ADM1.
AB - Wastewater characterization as required for implementation in ADM1 is based on
the identification of the numerous concentrations of the specific compounds
defined in ADM1. However, identification of the individual substrate
concentrations requires specific analytical techniques and in most cases only
general measurements like COD, TOC, and organic nitrogen are available. This
paper describes a simple method for calculation of the lumped elemental
composition of the organic substrates in the wastewater from a limited number of
widely available analyses. Using the elemental composition of the lumped
substrate and the elemental composition of the substrates defined in the model,
the influent composition as required for input in ADM1 can be calculated.
Furthermore, proper waste characterization allows for an initial analysis of the
biogas flow rate and composition as well as the reactor pH that can be achieved
upon organic substrate degradation, as will be demonstrated. It is hoped that the
methods described in this paper will stimulate and simplify future application of
ADM1.
PMID- 17037183
TI - Enteral sedation for the dental practice.
PMID- 17037184
TI - Oral pathology quiz #52. Case number 1. Squamous cell carcinoma.
PMID- 17037185
TI - A tale of two officers: life in the Dental Corps.
PMID- 17037186
TI - The marketplace for selling your practice.
PMID- 17037187
TI - Blood pressure monitoring in the dental setting.
PMID- 17037188
TI - [Progresses in the structure and function of Kazal-type proteinase inhibitors].
AB - Proteinase inhibitors are widely distributed in many living organisms and play
crucial roles in many biological processes, particularly in regulating the
proteinase activity spatially and temporally. However, The Kazal family of serine
protease inhibitors is one of the most important and extensively studied protease
inhibitor families. This type of protease inhibitor normally consists of one or
several domains. Every domain has a highly conserved sequence structure and
molecular conformation. It is found that contact residues are hyper variable,
which are responsible for the interaction of inhibitors and proteinases. Most of
them are in the solvent exposed loop. But P1 residue is the key active site of
the interaction between inhibitor and enzyme. The types of the amino acid at P1
site likely play an important role in causing different inhibitory activity. The
substitutions at the contact residues cause significant effects on the
association constant. By using the Laskowski algorithm, the Ki values of a Kazal
domain against six serine proteinases can be predicted from the domain' s
sequence alone. At present there are many Kazal proteinase inhibitors found in
the organisms, which show important biological functions. This article gives a
comprehensive review of the newer developments in the characters and the
interaction of the Kazal-type inhibitors.
PMID- 17037189
TI - [Identification of mimotope peptides which bind to the SARS-CoV spike protein
specific monoclonal antibody 2C5 with phage-displayed peptides library].
AB - To identify the epitope of SARS-CoV spike protein specific neutralizing
monoclonal antibody (MAb) 2C5. The antibody was used as target and three rounds
of bio-panning were conducted with phage-display peptide library. After the third
panning, 20 phage-plague clones were randomly picked and analyzed for the binding
ability with the MAb 2C5 by ELISA. The display sequence analysis demonstrated
that among the twenty phage clones, eight clones displayed the same seven-peptide
TPEQQFT. All these eight phage-clones showed strongest binding activity with 2C5
in phage ELISA analysis. Furthermore, phages displaying peptide TPEQQFT could
specifically inhibit the binding of MAb 2C5 with SARS-CoV spike protein. The
results demonstrated that TPEQQFT is a mimic epitope peptide containing
neutralizing MAb 2C5. This study may provide information for further structural
and functional analysis of spike protein and development vaccine for severe acute
respiratory syndrome.
PMID- 17037190
TI - [Organization and transcription strategy of genome of Bombyx mori bidensovirus
(China isolate) VD1].
AB - To better understand the genomic structure and function of Bombyx mori
bidensovirus (China isolate) VD1, the VD1 was purified and cloned into the pUC119
vector, and the complete nucleotide sequence of VD1 was determined. Sequence
analysis showed that VD1 genome consisted of 6543 nts including inverted terminal
repeats (ITRs) of 224 nts. In the viral genome, three major open reading frames
(ORF1, ORF2 and ORF3) in the plus strand and one major ORF (ORF4) in the
complementary strand were identified. Comparison of the complete genome sequence
between Bombyx mori bidensovirus (China isolate) and BmDNV-2 (Yamanashi isolate)
showed an identity of 98.4% in VD1, with a total number of 104 bp substitutions
and 1 bp insertions found in Bombyx mori bidensovirus (China isolate), the highly
variable regions were mainly located in VD1 ORF3 and VD1 ORF4. Northern blotting
revealed that VD1 contained 1.1 kb and 1.5 kb transcript in the left-half 'plus'
strand, and one transcript about 3.3 kb of 'minus' strand in the right-half.
Sequencing of 3' and 5' ends of transcript products showed the 1.1 kb transcript
started at nt 290 and ended at nt 1437, the 1.5 kb transcript was found to start
nt 1423 and ended at 2931, and the 3.3 kb transcript was found to start nt 6287
and ended at nt 2922. Therefore, the 1.5 kb transcript in the left-half plus'
strand and 3.3 kb transcripts of minus' strand in the right-half overlapped for
10 nts at the 3' ends. These results indicate that this virus employs a
transcription strategy that is radically different from that of the other
reported DNVs.
PMID- 17037191
TI - [The construction of recombinant adenovirus expressing bifunctional fusion
protein sCAR-EGF and the detection of its activity].
AB - To improve the targeting of adenovirus vector for gene therapy, a fusion gene
sCAR-EGF, in which epidermal growth factor gene was fused to the 3' end of
extracellular Coxsackie virus-adenovirus receptor gene, was constructed and
cloned into shuttle plasmid pDC315 to obtain a recombinant plasmid pDC315-sCAR
EGF. With the AdMax system, AD-293 cells were co-transfected with pDC315-sCAR-EGF
and adenovirus genomic plasmid pBHGloxdeltaE13cre. Through high efficiency site
specific recombination, a replication-defective adenovirus Ad5-CMV-sCAR-EGF was
constructed. The recombinant adenovirus was analyzed by PCR and Western blotting,
the results indicated that Ad5-CMV-sCAR-EGF contained the fusion gene sCAR-EGF,
and the adenovirus infected cells was induced to produce and secrete the fusion
protein into the supernatant. We have demonstrated that the fusion protein sCAR
EGF is helpful for elevating the infection efficiency of Ad5-CMV-luc with the
reporter gene in vitro, which providing a new approach to the gene therapy for
tumors overexpressing EGFR.
PMID- 17037192
TI - [Generation high yield vaccine strain wholly derived from avian influenza viruses
by reverse genetics].
AB - Highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtypes caused
enormous economical loss to poultry farms in China and Southeastern Asian
countries. The vaccination program is a reliable strategy in controlling the
prevalence of these disastrous diseases. The six internal genes of the high-yield
influenza virus A/Goose/Dalian/3/01 (H9N2), the hemagglutinin (HA) gene of
A/Goose/HLJ/QFY/04 (H5N1) strain, and the neuraminidase gene from
A/Duck/Germany/1215/73 (H2N3) reference strain were amplified by RT-PCR
technique. The HA gene was modified by the deletion of four basic amino acids of
the connecting peptide between HA1 and HA2. Eight gene expressing plasmids were
constructed, and the recombinant virus rH5N3 was generated by cells transfection.
The infection of chicken embryos and the challenge tests involving chickens
demonstrated that the recombinant H5N3 (rH5N3) influenza virus is avirulent. The
allantoic fluids of rH5N3-infected eggs contain high-titer influenza viruses with
hemagglutination unit of 1:2048, which are eight times those of the parental H5N1
virus. The rH5N3 oil-emulsified vaccine could induce hemagglutination inhibition
(HI) antibodies in chickens in 2 weeks post-vaccination, and maximum geometric
mean HI-titer were observed 4 approximately 5 weeks post-vaccination and were
kept under observation for 18 weeks. The rH5N3-vaccinated chickens were fully
protected against morbidity and mortality of the lethal challenge of the H5N1
HPAI viruses, A/Goose/Guangdong/1/96 and A/Goose/HLJ/QFY/04, which had 8 years
expansion and differences among multiple amino acids in HA protein. The N3
neuraminidase protein marker makes it possible to distinguish between H5N1
infected- and H5N3 vaccinated animals.
PMID- 17037193
TI - [Cloning and analysis of phage Fab antibodies of mouse male specific antigen].
AB - To clone mouse phage antibodies against H-Y antigen from a phage antibody
library, three cycles of affinity enrichment of the mouse phage antibody library
with male spleen cells and two cycles of nonspecific absorption with female
spleen cells were performed. The presence of mouse Fab on the phage surface was
determined by ELISA and sequence analysis. 9 of 15 strains can bind to male
spleen cells with the specific activity. Recombination rate of the phage antibody
library clones is 60%. Sequence analysis of the PCR products of plasmid DNA of E5
clones show VH and Vkappa had common characteristics shared by other known
variable region of antibodies. The mouse phage Fab antibody could be used for
identifying H-Y antigen, and for the development of sex determination of early
embryos in mammals.
PMID- 17037194
TI - [Fusion expression of O type foot-and-mouth diseases virus VP1 gene and HSP70
gene and induction of immune responses in mice].
AB - Vp1 gene of O type foot-and-mouth diseases virus and M. tuberculosis HSP70 were
expressed in methylotrophic yeast Pichia pastoris expression system. The results
of cellular immune responses and humoral immune response were examined after
BALB/c mice were immunized with fusion protein expressed in methylotrophic yeast
Pichia pastoris. The genes was cloned into the vector pPICZalpha-A by routine
molecular technique. The plasmid fusion (pPICZalphaA-vp1-HSP70) was created that
HSP70 located downstream of VP1 gene of O type foot-and-mouth disease virus. Vp1
was expressed by fusing to the amino terminus of M. tuberculosis hsp70 in yeast
Pichia pastoris. The recombined fusion plasmid was transformed into
methylotrophic yeast Pichia pastoris X-33 by electrophoration. The recombinant
transformants were selected by Zeocin and induced by the addition of methanol
every 24h. The expressived product analyzed by SDS-PAGE and Western blotting. The
result indicated that the fusion protein(vp1-HSP70) has specific antigenicity.
Mice were inoculated transcutaneous three times at a two-weeks interval with
fusion protein, PBS and conventional inactivated vaccines. To evaluate the
prophylaxtic efficacy of fusion protein, Titers of antibodies was detected by
ELISA and proliferation of lymphocytes were determined by MTT. The results
indicated that fusion protein could elicit specific humoral immune and cellular
immune responses. Compared with conventional inactivated vaccines, fusion protein
elicited slightly lower FMDV antibody level but stronger T cell proliferation.
PMID- 17037195
TI - [Cloning, prokaryotic expression of chicken interferon-alpha gene and study on
antiviral effect of recombinant chicken interferon-alpha].
AB - The full length of chicken interferon alpha (ChIFN-alpha) gene was amplified by
the polymerase chain reaction (PCR) from total liver genome of Sanhuang meat
chicken and sequenced. The amplified gene was about 582bp. The coding region for
mature protein (489bp) was subcloned into pET-28a(+). The recombinant plasmid pET
28a(+)-IFNalpha was identified by enzyme digestion and DNA sequencing. Data of
SDS-PAGE and Western-blot indicated that a 22kD fusion protein was expressed in
the form of inclusion bodies with good immunity. The purity of inclusion bodies
was above 70% and that of protein purified by nickel affinity chromatography was
95%. The recombinant protein could inhibit H9N2 avian influenza virus (H9N2 AIV)
replication on chick embryo fibroblast. 2 microg of recombinant IFN-alpha could
completely protect Chick embryo from H9N2 AIV infection. The recombinant IFN
alpha can also delay Newcastle disease virus (NDV) replication on chick embryo
for 12 approximately 48h. Chicken administered recombinant IFN-alpha can resist
the H9N2 AIV infection. The bioactivities of recombinant IFN-alpha purified by
affinity chromatograph were 20 times higher than that of inclusion bodies.
PMID- 17037196
TI - [Produce of marker-free transgenic tobacco plants by FLP/frt recombination
system].
AB - Selectable marker genes that usually encode antibiotic or herbicide resistances
are widely used for the selection of the transgenic plants, but they become
unnecessary and undesirable after transformation selection. An important strategy
to improve the transgenic plants' biosafety is to eliminate the marker genes
after successful selection. In the FLP/frt site-specific system of the 2 microm
plasmid of Saccharomyces cerevisiae, the FLP enzyme efficiently catalyzes
recombination between two directly repeated FLP recombination target (frt) sites,
eliminating the sequence between them. By controlled expression of the FLP
recombinase and specific allocation of the frt sites within transgenic
constructs, the system can be applied to eliminate the marker genes after
selection. Through a series of procedures, the plant FLP/frt site-specific
recombination system was constructed, which included the frt containing vector
pCAMBIA1300-betA-frt-als-frt and the FLP expression vector pCAMBIA1300-hsp-FLP
hpt. The FLP recombinase gene was introduced into transgenic (betA-frt-als-frt)
tobacco plants by re-transformation. In re-transgenic plants, after heat shock
treatment, the marker gene als flanked by two identical orientation frt sites
could be excised by the inducible expression of FLP recombinase under the control
of hsp promoter. Excision of the als gene was found in 41% re-transgenic tobacco
plants, which indicated that this systerm could make a great contribution to
obtain the marker free transgenic plants.
PMID- 17037197
TI - [Gene cloning and expression analysis of a male sterility related gene BoDHAR
from broccoli].
AB - A differentially expressed cDNA fragment obtained from a cDNA-AFLP analysis,
which performed on floral buds of male sterile and fertile lines of cabbage, was
used as a querying probe to blast the Genbank and Arabidopsis databases. Based on
the assembled homologous cDNA sequences, a full-length cDNA of 633 bp for BoDHAR
was cloned by RT-PCR. Furthermore, we have experimentally cloned and sequenced
the 5' flanking sequence of gene BoDHAR by genomic walking method based on
ligation-mediated PCR. The full length DNA sequence with 1486bp, containing two
introns, was achieved. Homologous analysis shows that gene has 82.3% identity at
nucleotide level, and 79.6% identity at amino acid level with Arabidopsis
dehydroascorbate reductase (DHAR) gene AT1 G19570.1. Structurally, BoDHAR encodes
a polypeptide of 210 amino acids, which contains a GST-c-DHAR domain highly
conserved among other members of the DHAR superfamily and has multiple
phosphorylation sites. Promoter predictions software indicated that the 5'
upstream region contained putative transcription signals and conserved sequences,
one CAAT-box, one G-box and four TGAC-like motifs. To advance our understanding
of gene BoDHAR, tissue expression pattern were analyzed by semi-quantitative RT
PCR. The results indicate that expression level of gene BoDHAR is higher in
fertile buds than that in sterile buds, and expressed intensively in the anther.
PMID- 17037198
TI - [Activation of silent antibiotic synthesis in Streptomyces lividans by disruption
of a negative regulator nsdA, a gene conserved in Streptomyces].
AB - The global regulatory gene, nsdA, negatively regulates antibiotics production in
Streptomyces coelicolor. Southern blot experiment, using an nsdA fragment of S.
coelicolor as probe, indicated that nsdA gene existed in many Streptomyces.
Primers were designed based on the published sequences of S. coelicolor and S.
avermitilis. PCR amplification and sequencing showed that nsdA in Streptomyces
was conservative and that of S. lividans ZX64 has a 100% identity in the
nucleotide sequence comparing with that of S. coelicolor A3 (2). The nsdA
disrupted mutant of S. lividans was constructed named as WQ2. WQ2 was able to
produce actinorhodin but the wild-type strain ZX64 did not, which has a silent
gene cluster contributing to the biosynthesis of actinorhodin. However, the
ability was lost when another copy of the wild nsdA gene was introduced into WQ2.
All the results above indicate that nsdA homologous gene is wildly existent and
conserved in Streptomyces. And it plays a role in negatively regulating the
actinorhodin synthesis in S. lividans and disruption of it can activate the
silent gene cluster.
PMID- 17037199
TI - [The synthesis and function analysis of omega-3 fatty acid desaturase gene from
Caenorhabditis briggssae].
AB - Omega-3 polyunsaturated fatty acids (PUFAs) have been broadly investigated and
shown to exert many preventive and therapeutic actions besides their important
role in maintenances human health and normal development. In mammals, the level
of omega-3 PUFAs is relatively too low compared with omega-6 PUFAs, which
metabolically and functionally distinct from omega-3 PUFAs and often have
important opposing physiological functions. Either the inefficiency of omega-3
PUFAs or the excess of omega-6 PUFAs will cause many healthy problems. So methods
have been sought to increase the amount of omega-3 PUFAs and to improve the omega
6/omega-3 ratio in body. In this study, the sFat-1 gene, which putatively encodes
a omega-3 fatty acid desaturase, was chemically synthesized according to the
sequence from Caenorhabditis briggssae (with codon usage modified), and
constructed into a mammal expression vector pcDNA3. 1-sFat1-EGFP. This vector was
introduced into CHO cells by lipid-mediated transfection, and it's expression
quickly and effectively elevated the cellular omega-3 PUFAs (from 18-carbon to 22
carbon) contents and dramatically improved the ratio of omega-6/omega-3 PUFAs.
Cellular lipids extracts from stably selected cells were analyzed with GC-MS and
the results showed that amount of total omega-6 PUFAs dropped from 48.97% (in GFP
cells)to 35.29% (in sFat-1 cells), whereas the amount of total omega-3 PUFAs
increased from 7.86% to 24.02%, respectively. The omega-6/omega-3 ratio also
dropped from 6.23 to 1.47. These data demonstrates the Caenorhabditis briggssae
omega-3 Fatty Acid Desaturase gene, sFat-1, was synthesized successfully and can
produce omega-3 PUFAs by using the corresponding omega-6 PUFAs as substrates,
which shows its potential for use in the production of omega-3 PUFAs in
transgenic animals.
PMID- 17037200
TI - [The effect of human IL-17F on growth of human hepatocarcinoma xenograft tumor in
nude mice].
AB - The human interleukin-17F(hIL-17F) gene was amplified by RT-PCR from PHA
activated human peripheral blood mononuclear cells (PBMCs). It was then subcloned
into the retrovirus vector pSIV-1. The pSIV-1/hIL-17F together with its two
helper virus vectors pHIT456 and pHIT60 cotransfected into the package cell 293T
by lipofectin to produce mature recombinant retrovirus, which was then used to
infect SMMC-7721 hepatocarcinoma cells (HCCs), and the cells were selected in the
presence of G418. The integration, transcription, expression of hIL-17F gene in
SMMC-7721 cells was identified by PCR, RT-PCR and Western blot respectively. MTT
and FCM showed that hIL-17F couldn't alter the proliferation and cell cycle of
SMMC-7721 cells, but ELISA showed that it could down-regulate IL-6, IL-8 and VEGF
expression. The effect of rhIL-17F supernatant on growth suppressing of ECV304
cells was observed by MTT. The experiment of human hepatocarcinoma xenograft
tumor in nude mice showed that the formation and growth rates of hIL-17F
transgenic SMMC-7721 showed an obvious decline, and VEGF and CD34 expression and
angiogenesis of the transgenic neoplasms was also evidently defined. hIL-17F can
markedly inhibit the growth of human hepatocarcinoma xenograft tumor in nude mice
by antiangiogenesis. This study provided an experimental evidence for further
conducting tumor gene therapy by targeting vascularity and exploiting
antiangiogenic novel medicine related to hIL-17F.
PMID- 17037201
TI - [Gene construction, expression and activities analysis of human leptin].
AB - Six 89bp primers were designed on the base of the cDNA sequence encoding the
human leptin reported on the NCBI. The synthetic gene with 464bp encoding rhLep
was obtained by SOE ( splicing by overlap extension) PCR. The expression vector
pET22b(+)/rhLep was constructed and transformed into E. coli BL21 (DE3). The
rhLep protein was expressed as inclusion bodies with the yield of more than 50%
of total bacterial proteins after IPTG induction. The rhLep protein, which has a
molecular weight about 16kD, was purified by Ni2+ affinity chromatography column
and identified by SDS-PAGE. The MTT Assay shows that rhLep promotes EC304 cells
growth at the low concentration of 10ng/mL to 30 ng/mL, and rhLep appears
cytotoxic to EC304 cells with the high dose of 50ng/mL to 225ng/mL. The viability
of EC304 cells decreases to 1.2% with the concentration of 225ng/mL of rhLep. The
massive apoptosis of rhLep on EC304 cells is observed by AO-staining under
fluorescent microscope. All these results would lay the foundation for the
further study of its biological functions in vitro and in vivo.
PMID- 17037202
TI - [Transgenic mice produced by intracytoplasmic sperm injection].
AB - In our previous study, normal and fertile mice were successful produced from
oocytes following intracytoplasmic sperm injection (ICSI). In the present study,
the possibility of producing transgenic embryos and offspring with this procedure
was evaluated. After freezing-thawed once using HEPES-CZB medium without
cryoprotectants, the cauda sperm from KM fertile male were exposed to the
circular or linear pEGFP-N1 DNA for 1 min and then co-injected into metaphase II
oocytes of B6D2F1 strain. When the zygotes with two pronuclei were cultured in
CZB medium to day 3.5, 39.1% (9/23) of them, derived from oocytes co-injected
with sperm head and pEGFP-N1 plasmid DNA, were expressed GFP protein. After
transfer of the ICSI embryos with two pronuclei from co-injection of sperm head
and foreign DNA, seven recipients delivered 30 pups (23.8%, 30/126). Southern
blot results revealed that three of sixteen offspring integrated with GFP and
neomycin genes together (18.8 %). Interestingly, all of them were produced from
oocytes co-injected sperm head and linear DNA (33.3%, 3/9), while none of seven
ICSI offspring integrated either GFP or neomycin gene in the group of co
injection of sperm head and circular plasmid DNA. These results indicated that
the high efficiency of transgenic mouse could be produced by ICSI. It may be
shown that linear DNA is more easily to integrate into host genome than circular
DNA when ICSI was used to produce transgenic animals.
PMID- 17037203
TI - [Rapid detection of Pseudomonas aeruginosa by the fluorescence quantitative PCR
assay targeting 16S rDNA].
AB - The 16S rDNA specific primers were designed for rapid detection of Pseudomonas
aeruginosa (PA) by the fluorescence quantitative PCR (FQ-PCR) assay, based upon
multiple sequence alignment and phylogenetic tree analysis of the 16S rDNAs of
over 20 bacteria. After extraction of PA genomic DNA, the target 16S rDNA
fragment was amplified by PCR with specific primers, and used to construct
recombinant pMDT-Pfr plasmid, the dilution gradients of which were subjected to
the standard quantitation curve in FQ-PCR assay. Different concentrations of PA
genomic DNA were detected by FQ-PCR in a 20microL of reaction system with SYBR
Green I. At the same time, various genomic DNAs of Staphylococcus aureus,
Salmonella typhi, Shigella flexneri, Proteus vulgaris, Staphylococcus
epidermidis, Escherichia coli, and Mycobacterium tuberculosis were used as
negative controls to confirm specificity of the FQ-PCR detection assay. Results
demonstrated that the predicted amplified product of designed primers was of high
homology only with PA 16S rDNA, and that sensitivity of the FQ-PCR assay was of
3.6pg/microL of bacterial DNA or (2.1 x 10(3) +/- 3.1 x 10(2)) copies/microL of
16S rDNA, accompanied with high specificity, and that the whole detection process
including DNA extraction could be completed in about two hours. In contrast to
traditional culture method, the FQ-PCR assay targeting 16S rDNA gene can be used
to detect PA rapidly, which exhibits perfect application prospect in future.
PMID- 17037204
TI - [Preparation of new lipid-hydroxyapatite-DNA complex and gene transfection
reseach in eukaryotic cell].
AB - This work was directed at obtaining a better gene carrier to improve the effects
of gene delivery. Neutral liposomes made from cholesterol, lecithin and DOPE by
reverse evaporation technique were used for encapsulating DNA-HAP complex which
was made from DNA and optimized HAP. The sizes of complexes and the efficiency of
encapsulation were detected. The efficiency of transfection into Hela cells was
shown by observation of X-gal staining and measurement of transfection
efficience. The average size of complexes was 643nm, the average encapsulating
efficiency of DNA in microspheres reached 11.67%. These Lipid-Hydroxyapatite-DNA
complex (LHD) could be transfected into mammalian cells. The Lipid-Hydroxyapatite
DNA complex prepared by reverse evaporation technique could be applied availably
in DNA delivery system, and it gave another thinking to increase the gene
transfection of non- viral genetic vector.
PMID- 17037205
TI - [Production of gastrodin through biotransformation of p-hydroxybenzaldehyde by
cell suspension cultures of Datura tatula L].
AB - The conversion of exogenous p-hydroxybenzaldehyde to p-hydroxy-methyl-phenol-beta
D-glucoside (gastrodin) was studied by using cell suspension culture of Datura
tatula L. The chemical structure of this synthesized gastrodin was identified
based on the spectral analysis and chemical evidence. The conversion procedure of
p-hydroxybenzaldehyde into gastrodin by D. tatula L. cell suspension cultures was
established. The synthesized gastrodin (II) was isolated from the ferment liquor
and identified by spectral analysis. At the same time, the p-hydroxybenzyl
alcohol (I) converted through biotransformation of p-hydroxybenzaldehyde by cell
suspension cultures of D. tatula L. was also isolated and identified. The
efficiency of glucosylation of p-hydroxybenzaldehyde was remarkably enhanced by
adding salicylic acid (0.1 mg/L) and keeping the lower pressure (0.001MPa) in 25L
airlift loop bioreactor. The biotransformation of exogenous p-hydroxybenzaldehyde
to gastrodin by cell suspension culture of D. tatula L. is a promising approach.
PMID- 17037206
TI - [Effect of homogeneity on cell growth and anthocyanin biosynthesis in suspension
cultures of Vitis vinifera].
AB - The instability of secondary metabolite production is a ubiquitous problem in
plant cell culture. To understand the instability, the investigation of
anthocyanin accumulation in suspension cultures of Vitis vinifera, as a model
system, has been initiated in our laboratory. Suspension culture of a relatively
homogeneous cell line E of V. vinifera, was established by long-term cell line
selection by anthocyanin content differentiation. The aggregate size of E was
smaller than that of other cell lines obtained by routine screening method. The
variation coefficients of anthocyanin content in suspension cultures of E were
8.7% in long-term subcultures and 5% in repeated flasks, respectively. The
effects of elicitor, precursor feeding and light irridiation on biomass and
anthocyanin accumulation in suspension cultures of E had been investigated and
the results showed that all the variation coefficients were lower than 12% and
this indicated the importance of homogeneity on stable production in plant cell
culture. With the combination treatment of 30micromol/L phenylalanine and
218micromol/L methyl jasmonate in the dark in suspension cultures of E, the
anthocyanin content and production in suspension culture of E was 5.89-fold and
4.30-fold of the controls, respectively, and all the variation coefficients of
biomass and anthocyanin accumulation were lower than those of the controls in 5
successive subcultures.
PMID- 17037207
TI - [Refolding of the fusion protein of recombinant enterokinase light chain rEKL].
AB - The fusion protein of enterokinase light chain, DsbA-rEKL, was expressed mainly
in inclusion body in E. coli. The recombinant bacteria was fermented to high
density, with high expression of the fusion protein. After being washed with 0.5%
Triton X-100 and 4mol/L urea, the inclusion body was dissolved in 6mol/L
guanidine and 100mmol/L DTP, derivatized by cystine and refolded by pulse
refolding. The strategy of pulse refolding involved the addition of 0.03mg/mL of
fusion protein until its final concentration reached 0.3mg/mL. The refolded
protein was autocleaved and the active EKL molecule was released after adding
2mmol/L CaCl2. Using the two-step purification processes of IDA-Sepharose
chromatography and Q-Sepharose chromatography, the purity of rEKL was found to be
above 95%, with a high activity to cleave the recombinant reteplase fusion
protein Trx-rPA. The yield of purified rEKL was more than 60mg/L of cultures. As
a result, the therapeutic proteins like rPA could be produced on a large-scale in
a way such as expressed in the form of fusion proteins.
PMID- 17037208
TI - [Continuous ethanol fermentation coupled with recycling of yeast flocs].
AB - A continuous ethanol fermentation system composed of three-stage tanks in series
coupled with two sedimentation tanks was established. A self-flocculating yeast
strain developed by protoplast fusion from Saccharomyces cerevisiae and
Schizosaccharomyces pombe was applied. Two-stage enzymatic hydrolysate of corn
powder containing 220g/L of reducing sugar, supplemented with 1.5g/L (NH4)2HPO4
and 2.5g/L KH2PO4, was used as the ethanol fermentation substrate and fed into
the first fermentor at the dilution rate of 0.057h(-1). The yeast flocs separated
by sedimentation were recycled into the first fermentor as two different models:
activation-recycle and direct recycle. The quasi-steady states were obtained for
both operation models after the fermentation systems experienced short periods of
transitions. Activation process helped enhance the performance of ethanol
fermentation at the high dilution rates. The broth containing more than 101g/L
ethanol, 3.2g/L residual reducing sugar and 7.7g/L residual total sugar was
produced. The ethanol productivity was calculated to be 5.77g/(L x h), which
increased by more than 70% compared with that achieved in the same tank in series
system without recycling of yeast cells.
PMID- 17037209
TI - [Model study on CO2 removal by photobioreactor].
AB - The key point of study on CO2 removal by microalgae cultured in a photobioreactor
is to improve CO2 removal capability. In this paper, a model of air-lift
photobioreactor was developed by combination of conditions including the velocity
of flow, the degree of mixing, the gas-liquid mass transfer and the rate of
photosynthesis, and two corresponding simplified methods, such as time
discretization and lumped parameters were put forward. Using a method of lumped
parameters, the model for simulation of time course of DO, pH in the column air
lift photobioreactor and prediction of CO2, O2 concentrations in the outlet gas
under different CO2 concentration in the aeration gas was thoroughly discussed.
Experimental data were also used to verify the model which could potentially be
applied to rational design of the photobioreactor, high-density culture of
microalgae and efficient removal of CO2.
PMID- 17037210
TI - [The preparation of an elicitor from a fungal endophyte to enhance artemisinin
production in hairy root cultures of Artemisia annua L].
AB - The different components of crude mycelium of the predominant endophytic
Colletotrichum gloeosporioides of Artemisa annua have been extracted by the
methods of acid hydrolysate. We compared the effect of the isolated components on
artemisin biosynthesis in hairy root cultures. Therefore, the oligosaccharide
elicitor from C. gloeosporioides has been partially purified by column
chromatography of Sephadex G25. The isolated oligosaccharide B II (elicitor, MW <
2500) has been revealed to promote the production of artemisinin in Artemisia
annua hairy root cultures. When hairy roots of 23-day old cultures (later growth
phase) were exposed to the elicitor at 0.4 mg/mL for 4 days, the maximum
production of artemisinin reached to 13.51 mg/L, a 51.63% increase over the
control. This is the first report on the stimulation of artemisinin production in
hairy roots by the oligosaccharide elicitor from an endophytic fungus of A.
annua.
PMID- 17037211
TI - [Isolation and characterization of gamma-TMT gene promoter from Arabidopsis
thaliana].
AB - Vitamin E (Tocopherols) is lipid-soluble antioxidants and essential for human
health. Gamma-tocopherol methyltransferase (delta-TMT), one of the key enzymes in
tocopherol biosynthetic pathway in plants, converts delta,sigma-tocopherols into
alpha,beta-tocopherols. In this study, we isolated the 1552 bp promoter of
Arabidopsis TMT gene. The promoter was fused with GUS reporter gene and this
expression cassette was introduced into wild Arabidopsis thaliana by
Agrobacterium-mediated transformation. GUS staining shows that GUS gene is
expressed in leaves, stems and flowers, with the highest expression in young
leaves, stamens and stem apices, while not observable in roots, seeds and
siliques. The data indicate that gamma-TMT gene promoter is likely to be
expressed preferentially in some of the tissues of Arabidopsis.
PMID- 17037212
TI - [Process performance of simultaneous anaerobic sulfide and nitrate removal].
AB - The process performance of simultaneous anaerobic sulfide and nitrate removal was
studied. The results showed that the process held a high sulfide and nitrate
removal loading rate of 3.73kg/(m3 x d) and 0.80kg/(m3 x d), respectively, under
steady state. It was capable of tolerating high influent substrate concentration
(580mg/L and 110mg/L) with the optimum substrate concentration of 280mg/L and
67.5mg/L. It was capable of tolerating short hydraulic retention time (HRT) with
the optimum HRT of 0.13d. Careful operation was needed when HRT was shortened
because the process performance was deteriorated abruptly.
PMID- 17037213
TI - [Study on vitrification of porcine embryos by open pulled straw method].
AB - 291 embryos (Blastocyst/Morula) from 20 donor sows were vitrified by two step
method with OPS (open pulled straw) in solution I (TCM199 + 20% FBS + 10% EG +
10% DMSO) for 3min, and solution II (TCM199 + 20% FBS + 20% EG + 20% DMSO +
0.4mol/L SUC) for 1min, stored in liquid nitrogen for 3 months, and transferred
into 8 recipient sows after warming, one recipient sow was pregnant and 8 alive
piglets were born. This is the first paper to report getting alive piglets by
vitrification in China.
PMID- 17037214
TI - [Effects of resveratrol on pig primary preadipocytes proliferation,
differentiation and transcription expression of Sirt1 gene].
AB - 1 approximately 3 days old Piglet's primary preadipocytes in vitro were cultured
and treated with 0micromol/L (control group), 10microlmol/L (lower dose group),
20micromol/L(middle dose group) and 50micromol/L, 100micromol/L (higher dose
group) RES. Cell proliferation and viability were analyzed by MTT assay. The
degree of differentiation and adipogenesis were measured by Oil Red O staining
extraction assay and the expression of Sirt1 (sirtuin) mRNA were detected by RT
PCR. The results showed the optical density (OD) of MTT and Oil Red O staining
were all decreased, especially treated by 50micromol/L, 100micromol/L RES at 72h
and 96h (P < 0.01); the ratio of OD of the expression of Sirt1 mRNA to that of
beta-actin mRNA were increased after treated by 100micromol/L RES (P < 0.01). RES
can inhibit proliferation and differentiation of pig preadipocytes in certain
degree. Higher dose of RES can markedly decrease adipogenesis and prevent
preadipocytes differentiation into adipocytes, which may be in part associated
with its effect on increasing the expression of Sirt1 mRNA.
PMID- 17037215
TI - [Application of optical proteinchip in detecting phage M13KO7].
AB - Avidin layer was bound on the substrate surface of Silicon wafer modified with
aldehyde. The interaction between avidin and biotin was adopted for the
immobilization of mouse monoclonal biotin-anti-M13 (antibody GP3)-labeled biotin.
The surface was incubated in a solution containing phage M13KO7, which was
trapped by the antibody GP3 with the interaction between phage M13KO7 and
antibody GP3, resulting in a variation of layer thickness that was detected by
imaging ellipsometry. The results showed a saturated layer of antibody GP3 with a
thickness about 6.9 nm on the surface of the silicon wafer. The specific
interaction between phage M13KO7 and antibody GP3 resulted in a variation of the
layer thickness. The layer of phage M13KO7 bound with antibody GP3 was 17.5 nm in
the concentration of 1.1 x 10(10) pfu/mL. Each variation of layer thickness
corresponded to a concentration of phage M13KO7 in the range of 0.1 x 10(10)
approximately 2.5 x 10(10) pfu/mL, with the sensitivity of 10(9) pfu/mL. Compared
with other methods, the optical protein-chip requires only short measurement
time, is label free, is a quantitative test, and can be visualized. This study
could be significant on the investigation of interactions between the antibody
and virus, and shows potential in the early diagnosis of virosis.
PMID- 17037216
TI - [The advancement of AFLP technology].
AB - AFLP technology has been widely used in molecular biology due to its integration
of several advantages of high throughput, high efficiency and requiring no
sequence information, etc. Great changes have been achieved in recent years in
AFLP-related technologies and platforms. There are several AFLP-expanded
technologies available. These improved technologies are capable of distinguishing
the heterozygote from the homozygote and of converting any AFLP band of interest,
without much effort, into locus-specific markers, which can be deployed for
massive locus detection and for gene isolation. This review focuses on these
favorable changes from conventional AFLP technology into more effective and more
practicable AFLP-related ones. Understanding these advancements and AFLP-expanded
technologies will facilitate the achievement of our research goals.
PMID- 17037217
TI - Infant feeding in Saudi Arabia: mothers' attitudes and practices.
AB - We conducted a nationwide cross-sectional survey of 4872 mothers (mostly Saudi)
to study infant feeding patterns. Information was collected about their feeding
practices with their youngest child using pre-tested questionnaires. About four
fifths of the mothers had received health education about breastfeeding, most
often from medical staff; younger mothers tended to be better informed.
Approximately 92% fed colostrum to the newborn, but 76.1% had introduced bottle
feeding by 3 months (48.3% cited insufficient milk as the reason for introducing
the bottle). This was significantly related to nationality and education level.
Mixed feeding (breastfeeding and bottle-feeding) was popular. Solid foods tended
to be introduced late and this was significantly related to nationality, age and
education level.
PMID- 17037218
TI - Epidemiological study of measles in Ghazvin, Islamic Republic of Iran, April 1997
April 2003.
AB - We studied measles incidence and morbidity in Ghazvin district by retrospective
review of cases registered at the central health office and admitted to two
hospital in Ghazvin city during April 1997-April 2003. There were 824 clinically
confirmed cases of measles over the 6-year period giving a mean annual incidence
of 18.67 per 100 000 population, higher than for the country generally. There
were no deaths from measles. Of the 824 cases, 591 (71.1%) had serum specimens
for serological analysis and 199 (24.3%) were confirmed serologically. Of the
serologically confirmed cases, the greatest proportion (44.2%) were over 20 years
(median age was 17.5 years), 54.5% had been in contact with a measles case and
21.6% cases had received 2 doses of vaccine. We studied 33 serologically
confirmed hospitalized cases. Common complications were vomiting (45.5%),
diarrhoea (42.4%) and pneumonia (21.2%). The mean duration of hospitalization was
3.8 days.
PMID- 17037219
TI - Evaluation of child deaths registration in a Jordanian community.
AB - A retrospective population-based household survey was conducted in Deir-Alla
district during July-August 2002. The aim was to determine the extent of under
registration of child deaths and stillbirths, estimate infant mortality and under
5 mortality rates and identify factors affecting under-registration. We
interviewed 1024 women aged 15-49 years about deaths in the last 3 children born.
A modified version of the preceding birth mortality questionnaire was used. We
found 72.2% of child deaths, including all 45 stillbirths, were unregistered.
Under-registration was significantly related to child's age at death, stillbirths
and dead infants < 1 year being more likely to be unregistered. The officially
published infant mortality rate is not a credible indicator of infant deaths.
PMID- 17037220
TI - Knowledge, attitudes and practices of secondary-school pupils in Oman: I. health
compromising behaviours.
AB - We investigated the practice of some of health-compromising behaviours among
Omani adolescents and their correlates in a nationally representative secondary
school-based sample of 1670 boys and 1675 girls. The mean age of the sample was
17.13 (SD 1.35) years. Through a self-administrated questionnaire the adolescents
were asked about 6 risky behaviours: current smoking, ever use of alcohol,
succumbing to peer pressure to take illicit drugs, driving without a licence,
speeding while driving and being involved in a physical fight in the month prior
to the survey. Demographic and psychosocial variables related to their risk
behaviours were also assessed. The results indicated that 4.6 % were current
smokers, 4.3% had drunk alcohol and 4.6% had taken drugs. About 20% had been
involved in a physical fight in the month prior to the survey, 33.4% drove
without a licence and 33.9% liked to speed. Male sex and low self-esteem were the
strongest predictors of risky behaviour.
PMID- 17037221
TI - Knowledge, attitudes and practices of secondary-school pupils in Oman: II.
reproductive health.
AB - We examined the knowledge, attitudes and practices of Omani adolescents with
regard to reproductive health in a nationally representative secondary school
based sample of 1670 boys and 1675 girls. Through a self-administrated
questionnaire the adolescents were asked about puberty, marriage, birth spacing
and AIDS and sexually transmitted infections. Only half of the sample knew the
changes at puberty of their own sex, while even fewer knew the changes in the
opposite sex. Girls were inclined significantly towards later age of marriage
than boys. The mean number of children desired by the sample was 4.9. About two
thirds of the adolescents had a positive attitude toward modern contraceptive
methods and intended to use them in the future. Knowledge of fertility period was
poor as was knowledge of AIDS and sexually transmitted infections. There was a
high rate of approval (80%) of female genital cutting by both sexes.
PMID- 17037222
TI - Depression in adolescents: gender differences in Oman and Egypt.
AB - To investigate the differences between adolescent boys and girls, the rates of
depression and associated factors were determined for secondary school
adolescents in 2 different samples, 552 in South Sharqiya, Oman, and 1577 in
Alexandria, Egypt. Multivariate logistic regression models were used to
investigate the correlates of depression. In Alexandria, the rate of having
depressive symptoms in girls was almost double that in boys. In Oman, however,
there was no significant difference. History of abuse during adolescence
predicted depression in almost all the models. Poor relationship with parents
affected girls more than boys in Alexandria and in the merged sample. Gender
differences in rates or correlates of depression exist but may differ for
different countries.
PMID- 17037223
TI - Post-traumatic stress disorder in children witnessing a public hanging in the
Islamic Republic of Iran.
AB - A study was made of post-traumatic stress disorder in 200 children aged 7-11
years who had witnessed a public hanging next to their school in Isfahan, Islamic
Republic of Iran. A standard checklist was completed through interviews with the
children's parents 3 months after the event. Post-traumatic stress disorder
symptoms were identified in 104 children (52%), with 88 suffering re-experiences,
24 avoidance and 62 hyperarousal. The mean stress severity according to the Child
Post-Traumatic Stress Reaction Index was 39.1, indicating a moderate to severe
severity of stress. The study highlights the serious emotional effects on
children who witness traumatic events.
PMID- 17037224
TI - Pattern of motorcycle-related injuries in Tehran, 1999 to 2000: a study in 6
hospitals.
AB - We studied motorcycle-related injuries in Tehran from 23 August 1999 to 21
September 2000 in 6 hospitals. Data were obtained from the trauma registry and
questionnaires completed by trained physicians. Of a total of 8500 patients with
trauma injuries, 1332 were motorcyclists, with a male to female ratio of 15:1. Of
these, 1226 patients were driving the motorcycle at the time of the accident and
75 were pillion passengers. Crashes involving another vehicle were the commonest
kind of accident (72.5%). Helmet use was noted in only 8.6% of cases. There were
28 fatalities and head injuries were the prominent cause of death. Of those who
died, none had been wearing a helmet at time of the crash. Only 2.7% of helmeted
riders sustained a head injury, compared with 11.2% of riders without a helmet.
The commonest musculoskeletal injury was fracture: tibial fracture with 509 cases
(49.8%) comprised the largest proportion.
PMID- 17037225
TI - Predictors of cardiovascular risk factors in Tehranian adults: diet and
lifestyle.
AB - We carried out a dietary intake assessment in 486 adults 20 from the Tehran Lipid
and Glucose Study. There was a strong positive association between body mass
index (BMI) and serum triglycerides (beta = 1.6, P < 0.05) and carbohydrate
intake and triglycerides (beta = 2.4, P < 0.05). There was also an association
between low-density lipoprotein cholesterol and weight (beta = 1.1, P < 0.05),
age (beta = 1.6, P < 0.05) and cholesterol intake (beta = 0.7, P < 0.01). For 1
unit increase in either BMI, waist to hip ratio or saturated fatty acid intake,
diastolic blood pressure increased 0.6, 0.9 and 0.1 mmHg, respectively (P <
0.05). Dietary and non-dietary factors have an association with, and play a role
as predictors of, CVD risk factors.
PMID- 17037226
TI - [Quality of ambulatory care of non-insulin dependent diabetic patients].
AB - We assessed the quality of care provided to non-insulin treated diabetic patients
by examining the medical records of 248 such patients attending our outpatient
department in 2002. The mean age was 59.5 (SD 10.1) years, 62.1% were women and
known duration of diabetes was 8.6 (SD 5.9) years. The majority of patients were
treated with a combination of sulfonylurea and metformin. Glycaemic control was
assessed using fasting blood glucose in 96.8% of patients, post-prandial blood
glucose in 31.9% and glycated haemoglobin in 52.4%. Weight was measured at least
once for 88.7% of patients, blood pressure for 91.1% of patients and lipid levels
for 64.9%. Body mass index was less than 25 kg/m2 in 12.3% of patients and blood
pressure less than 140/90 mmHg in 40.3%. Foot examination was noted in only 2% of
records, electrocardiography was performed for 25% of patients and fundoscopy for
21%. Proteinuria was documented in 19.8% of patients and plasma urea and/or
creatinine in 57.3%.
PMID- 17037227
TI - Frequency of peptic ulcer disease during and after Ramadan in a United Arab
Emirates hospital.
AB - We aimed to study the effect of Ramadan fasting on the occurrence of peptic ulcer
disease and its complications in patients presenting to the Accident and
Emergency Department at Al-Ain hospital, United Arab Emirates (UAE). We
retrospectively reviewed patient records over the 10-year period, 1992 to 2002.
Of 470 patients treated for peptic ulcer disease, 215 were seen during Ramadan
and 255 in the month after Ramadan. The frequency of peptic ulcer disease was
higher after Ramadan than during Ramadan but this was not statistically
significant. Peptic ulcer disease occurred more frequently in the age group 30-49
years. Peptic ulcer perforation occurred more frequently after Ramadan but the
difference was not significant. Regression analysis identified the following
variables as predictors of peptic ulcer disease: anorexia, pain, hypertension,
smoking, epigastric pain, diabetes and family history.
PMID- 17037228
TI - Seroepidemiology of selected zoonotic infections in Basra region of Iraq.
AB - A community-based seroepidemiological study was made of 4 common zoonotic
infections (brucellosis, hydatidosis, toxoplasmosis and visceral leishmaniasis)
in 3 areas (rural, urban and suburban semirural) in Basra governorate, southern
Iraq. The prevalence of brucellosis was higher in the suburban semirural area
(29.3%) than the rural and urban areas. The prevalence of hydatidosis (19.0%
35.5%) and toxoplasmosis (41.1%-52.1%) were relatively high in all 3 areas. With
respect to visceral leishmaniasis, low rates of infection were reported (0.2%
1.9%). The study shows in general that the suburban semirural area is at highest
risk of zoonotic infections compared with other areas. The results could form a
rational basis for the planning of an integrated comprehensive approach for
control of zoonotic infections in the areas surveyed.
PMID- 17037229
TI - Prevalence of bovine and human brucellosis in western Algeria: comparison of
screening tests.
AB - A serological study was carried out in Tiaret province in western Algeria on 1032
cows distributed in 95 flocks to estimate the prevalence of Brucella infection
and to compare the sensitivity and specificity of a range of agglutination tests.
Screening tests showed 31.5% of herds positive using the buffered plate antigen
test and 26.3% using the rose Bengal test compared with 15.7% with the complement
fixation test. Using the complement fixation test as the gold standard for
confirmatory tests, the Rivanol test was found to be more sensitive but less
specific than tube agglutination in detecting brucellosis infection. Three
isolates were identified from 105 blood samples from humans with brucellosis and
50 samples of milk and tissues from infected cows and they were all Brucella
melitensis biovar 3.
PMID- 17037230
TI - [Cleaning and molluscicide treatment for schistosomiasis control].
AB - We evaluated the effect of niclosamide treatment and the additional cleaning of
basins and pools on the density and infection rate of Bulinus truncatus within
the irrigation network of Oudaya. The period prior to molluscicide treatment
(January-May) revealed a mean density of 151 snails/m2 in 1995-96 and 127
snails/m2 in 1997-98. After cleaning had started, the mean density prior to
molluscicide treatment fell to 84 snails/m2 in 1999-2000. After molluscicide
treatment, densities dropped to very low levels only rising again from October.
In November 1999-96 mean density reached 150 snails/m2 but after cleaning started
in 1997-98 this only reached 80 snails/m2; in 1999-2000, when cleaning was
undertaken 3 months before and after molluscicide treatment, it reached only 18
snails/m2. From 1995 to 1996, the infection rate rose slightly (4.54% to 5.44%),
but, from 1997, there was a significant drop (3.13% to 2.16%).
PMID- 17037231
TI - Helminth eggs in raw and treated wastewater in the Islamic Republic of Iran.
AB - To assess the type and load of helminths in wastewater and the quality of
treatment, we examined the raw and treated wastewater of 8 wastewater treatment
plants (WTP) in Tehran and 2 in Isfahan for the presence of helminth eggs during
2002-2003. Wastewater samples obtained from both inlet and effluent of each
treatment plant were examined on several occasions using the modified Bailenger
method. Untreated entry wastewater in Tehran WTPs contained a larger variety of
helminth eggs than those of Isfahan, as well as higher total egg counts. The
helminths identified in the influent of Tehran included Ascaris lumbricoides,
hookworms, Enterobius vermicularis, Trichostrongylus spp., Taenia spp.,
Hymenolepis nana and Dicrocoelium dendriticum, while in Isfahan only A.
lumbricoides, Trichostriogylus and H. nana were isolated. After treatment, the
number of eggs/L fell to < or = 1 egg/L.
PMID- 17037232
TI - Housing conditions and health in Jalazone Refugee Camp in Palestine.
AB - We investigated some of the housing conditions at Jalazone Refugee Camp and their
impact on refugees' health inside the camp, especially those with respiratory
symptoms and diseases. A randomized sample of 200 housing units, representing one
fifth of the camp's population, was selected. Approximately half of the people in
our sample were under 15 years. Overcrowding and high population density were
significant. There was a statistically significant relationship between some
respiratory conditions (common cold, cough, tonsillitis and ear infection) and
poor housing conditions (including damp and mould), overcrowding and high
population density. A radical solution for the housing problem is needed to avert
further negative health impacts.
PMID- 17037233
TI - Dentists' perceptions of occupational hazards and preventive measures in East
Jerusalem.
AB - Dentists, like other health professionals, are exposed to various occupational
health problems, with specific ones of their own. A randomly distributed sample
of 40 (42.2%) dentists working in East Jerusalem was interviewed. A questionnaire
was used to detect their perception of occupational hazards. Most respondents
were aware of biological hazards: 38% specifically mentioned hepatitis B virus
and 13% human immunodeficiency virus. Perceived sources of stress included
factors that coincided with international data, such as relationships with
patients, physical strain and economic pressure, but also some specific to the
Palestinian culture such as relationships with other dentists and Israeli
occupation tax policy when dealing with the Arab dentists in East Jerusalem.
Chemical dependency was not mentioned as a potential hazard.
PMID- 17037234
TI - Audit of prescribing practices of topical corticosteroids in outpatient
dermatology clinics in north Palestine.
AB - To analyse the prescribing pattern of topical corticosteroids, 802 outpatient
dermatology prescriptions were randomly collected during June 2003-September 2003
from all the 12 nongovernmental dermatological clinics in north Palestine. Of the
2458 medications prescribed, 616 were topical corticosteroids. In most
prescriptions, information about strength, duration of treatment and quantity to
be used was inadequate, while information regarding frequency, route and area of
application was adequate. High efficacy and highest efficacy corticosteroids were
prescribed for approximately 18% of patients; intermediate efficacy preparations
were prescribed for approximately 50%.
PMID- 17037235
TI - National Register for the Blind: a tool for health programme management.
AB - We carried out a retrospective analytical study of 3525 bilaterally blind people
registered in Oman to the end of 2000. We described the examination method,
maintenance of the register and analysis of data. Lists of different categories
of blind people were distributed to various organizations for management and
rehabilitation purposes. The role of the national register in addressing blinding
cataract, corneal blindness, eradication of congenital rubella syndrome and care
of blind people in Oman was also examined. The register was useful in identifying
candidates for rehabilitation and also for monitoring regional efforts to manage
curable blindness. This multiple use of the register could make it an important
tool for health programme management in Oman.
PMID- 17037236
TI - Serum endostatin and vascular endothelial growth factor levels in patients with
pre-eclampsia.
AB - We evaluated the prognostic value of serum endostatin and vascular endothelial
growth factor (VEGF) for diagnosis of pre-eclampsia. We determined VEGF and
endostatin levels in the sera of 20 healthy, non-pregnant women and 64 pregnant
women: 20 healthy, 20 with mild pre-eclampsia and 24 with severe pre-eclampsia.
Serum levels of these factors in non-pregnant women were similar to those in
healthy pregnant women. However, serum levels were significantly higher with mild
or severe pre-eclampsia compared with normal pregnancies and significantly higher
with severe rather than with mild pre-eclampsia. Elevated levels significantly
increased risk more than severity of pre-eclampsia. VEGF and endostatin could be
used to differentiate between pre-eclamptic and normal pregnancies and to
discriminate mild pre-eclampsia from severe pre-eclampsia.
PMID- 17037237
TI - Effect of menopause and renal function on vitamin D status in Iranian women.
AB - The effects of menopause and renal function on serum parameters of the vitamin D
endocrine system were studied in a cross-sectional sample of 676 healthy women
aged 20-74 years in Shiraz. Low serum 25-hydroxyvitamin D (25-OHD) was found in
52.9% of the women. Serum parathyroid hormone (PTH) increased significantly over
the age span in premenopausal women (r= 0.13, P= 0.02). In premenopausal and
postmenopausal women, serum levels of 25-OHD, phosphorus and calcium were stable
across the age span. There was no significant correlation between creatinine
clearance or serum PTH (r= -0.016, P= 0.66) and 25-OHD (r= 0.012, P= 0.74). The
high prevalence of vitamin D deficiency warrants consideration of dietary
supplementation.
PMID- 17037238
TI - Monte Carlo simulation on the effect of different approaches to thalassaemia on
gene frequency.
AB - We used computer simulation to determine variation in gene, heterozygous and
homozygous frequencies induced by 4 different approaches to thalassaemia. These
were: supportive therapy only; treat homozygous patients with a hypothetical
modality phenotypically only; abort all homozygous fetuses; and prevent marriage
between gene carriers. Gene frequency becomes constant with the second or the
fourth strategy, and falls over time with the first or the third strategy.
Heterozygous frequency varies in parallel with gene frequency. Using the first
strategy, homozygous frequency falls over time; with the second strategy it
becomes constant; and with the third and fourth strategies it falls to zero after
the first generation. No matter which strategy is used, the population gene
frequency, in the worst case, will remain constant over time.
PMID- 17037239
TI - Seroprevalence of hepatitis C virus specific antibodies among Iraqi children with
thalassaemia.
AB - The seroprevalence of hepatitis C virus (HCV) specific antibodies and HCV
genotypes distribution were studied among 559 Iraqi children with thalassaemia in
receipt of repeated blood transfusions. HCV-specific antibodies were detected in
376 (67.3%) serum samples using third-generation enzyme immunoassay and
confirmatory immunoblot assays. Of 78 randomly selected sera, 48 (61.5%) were HCV
RNA positive. HCV genotypes 1a, 1b, 4 and mixed 1b and 4 were demonstrated in 13
(27.1%), 11 (22.9%), 17 (35.4%) and 7 (14.6%) sera respectively. Strict measures
for the controlling the spread of HCV are needed by introducing advanced
techniques for blood donor screening.
PMID- 17037240
TI - Flat foot among Saudi Arabian army recruits: prevalence and risk factors.
AB - This study determined the prevalence and risk factors for flat foot among 18-21
year-old male Saudi Arabian army recruits. Among 2100 military recruits, the
prevalence of flat foot was 5.0%. A case-control logistic regression analysis of
risk factors (104 cases and 412 controls) showed family history, wearing shoes
during childhood, obesity and urban residence were significantly associated with
flat foot. No associated complaints were reported among the cases and thus
flexible flat foot does not seem to be a cause of any disability.
PMID- 17037241
TI - [Patient archiving and communication systems: an example of the clinical
application of information technology].
AB - The applications of patient archiving and communication systems have increased
lately, particularly since the medical imaging companies began to distribute the
software along with machines. These systems are very important in developing
clinical work, particularly in critical care, for example following cardiac
surgery. This paper describes these systems and explores how they work, as an
example of the application of information technology in developing clinical work,
and critical care in particular.
PMID- 17037242
TI - Critical care medicine in Saudi Arabia.
AB - Critical care medicine remains underdeveloped in many parts of the world. In
Saudi Arabia, there have been major developments in the past 2-3 decades. The
purpose of this review is to give an account of the current status of critical
care practice (including services provided during the haj season) and training in
Saudi Arabia using examples of primary, secondary and tertiary care hospitals.
The future needs of the profession are also addressed.
PMID- 17037243
TI - Creatinine, blood urea nitrogen and thyroid hormone levels before and after
haemodialysis.
AB - A study was carried out on 57 patients with chronic renal failure in a hospital
in Kerman city, Islamic Republic of Iran. Blood samples were taken before and
after haemodialysis to measure blood urea nitrogen and serum creatinine,
triiodothyronine (T3) and thyroxine (T4) levels. Findings revealed that before
dialysis T4 in 11 cases and T3 in 29 cases were lower than the normal range, but
after haemodialysis only 3 cases for T4 and 15 cases for T3 were lower than
normal levels. The remaining cases reverted to normal state. We suggest that a
feedback relationship exists between the major end catabolic products (creatinine
and blood urea nitrogen) and thyroid hormone serum levels.
PMID- 17037244
TI - Distribution of malocclusion types in 7-9-year-old Iranian children.
AB - This study assessed the malocclusion types, very severe crowding and need for
serial extraction among a random sample of 7-9-year-old children in Shiraz,
Islamic Republic of Iran. Of the 3776 children 30.6% had normal occlusion, 47.4%
class I malocclusion, 13.7% class II division 1 malocclusion (male/female ratio
3:2), 1.0% class II division 2 malocclusion (male/female ratio 3:1) and 2.1%
class III malocclusion. Among the children examined, 47.9% had crowding problems
and 14.7% of them had class I malocclusion with very severe crowding-more girls
(17.3%) than boys (12.1%). No correlation was observed between the types of
malocclusion and family size, parents' occupation or level of education.
PMID- 17037245
TI - Cryptococcus neoformans var. gattii meningitis in Egypt: a case report.
PMID- 17037246
TI - Unusual association between renal tubular acidosis and Chilaiditi syndrome: a
case report.
PMID- 17037247
TI - Evaluating the community-oriented medical education in two medical schools in
Sudan.
PMID- 17037248
TI - [Avian influenza: a panic pandemia?].
PMID- 17037249
TI - DNA fingerprinting by ERIC-PCR for comparing Listeria spp. strains isolated from
different sources in San Luis, Argentina.
AB - In this study, a total of 24 Listeria spp. strains were analyzed. Twenty-two
isolates were obtained in San Luis (Argentina) from human, animal, and food
samples. Two types of strains, Listeria monocytogenes CLIP 22762 and Listeria
innocua CLIP 74915, were included as reference strains. All isolates were
biochemically identified and characterized by serotyping, phage typing, and
amplification of the flaA gene by polymerase chain reaction (PCR). Repetitive
intergenic consensus (ERIC) sequence-based PCR was used to generate DNA
fingerprints. On the basis of ERIC-PCR fingerprints, Listeria spp. strains were
divided into three major clusters matching origin of isolation. ERIC-PCR
fingerprints of human and animal isolates were different from those of food
isolates. In addition, groups I and II included ten L. monocytogenes strains, and
only one Listeria seeligeri strain. Group III included nine L. innocua strains
and four L. monocytogenes strains. Computer evaluation of ERIC-PCR fingerprints
allowed discrimination between the tested serotypes 1/2b, 4b, 6a, and 6b within
each major cluster. The index of discrimination calculated was 0.94. This study
suggests that the ERIC-PCR technique provides an alternative method for the
identification of Listeria species and the discrimination of strains within one
species.
PMID- 17037250
TI - [Modified EMJH medium for cultivation of Leptospira interrogans serogroup
ballum].
AB - Strains within the Ballum serogroup of spirochete Leptospira show fastidious
growth with more exigent nutritional requirements than those of other Leptospira
pathogenic strains. The influence of 37 nutritional compounds on the growth of
Leptospira interrogans serogroup Ballum was investigated employing the synthetic
EMJH medium as the base for the study. Microbial growth was estimated
spectrophotometrically and direct counts were performed with a Petroff-Hausser
counting chamber. Virulence stability was evaluated by calculating the mean
lethal dose in hamsters. Antigenicity stability was evaluated by Western blotting
using a specific antiserum. Cell yields commonly obtained in EMJH were
triplicated without virulence or antigenicity depletions after culturing in a
modified EMJH medium with an increased concentration of Tween 80, and the
incorporation of sodium acetate and beef extract. Neither the increased
concentration of at least 6 components of EMJH nor the incorporation of a variety
of new nutrients stimulated cell yields or the growth rate of the microorganism.
The results allow us to make use of an enriched culture medium that promotes high
cell yields of this fastidious serogroup most prevalent in humans in Cuba.
PMID- 17037251
TI - [Optimization of the growth of Paenibacillus larvae in semi-selective media].
AB - The sensitivity of media MYPGP, MYPGP(NALPIA) A (6 microg/ml nalidixic acid and
10 microg/ml pipemidic acid) and MYPGP(NALPIA) B (9 microg/ml nalidixic acid and
20 microg/ml pipemidic acid) for the recovery of viable spores of Paenibacillus
larvae from honey, was evaluated by using different incubation times and
different spore concentrations. No significant differences between incubation
times, spore concentration or culture media were found. In the case of the
recovery of vegetative cells from PBS at different incubation times and different
dilutions no significant differences were found between the incubation times or
the dilutions tested, while significant differences were found in the three media
when compared with one another, MYPGP(NALPIA)B providing the lowest recovery of
vegetative cells. Considering these results, we propose the use of MYPGP(NALPIA)B
to recover spores of P. larvae from honey, specially for honeys with
heterogeneous populations of bacterial spores; when culturing vegetative cells,
MYPGP or MYPGP(NALPIA)A must be used to obtain good growth.
PMID- 17037252
TI - [Helicobacter pylori and active chronic gastritis].
PMID- 17037253
TI - [Recombinant baculovirus as immunogens].
PMID- 17037254
TI - [Detection of anti-Brucella spp. antibodies in swine by agglutination techniques
and indirect ELISA in the Buenos Aires and La Pampa provinces, Argentina].
AB - Porcine brucellosis is one of the most important zoonoses in this country.
Currently, there is no control program for porcine brucellosis in Argentina and
the epidemiological situation is still unknown. The purpose of our study was to
detect anti-Brucella spp. antibodies in swine in the southwest of the Buenos
Aires province and the east of the La Pampa province. Blood samples were obtained
when animals were slaughtered. The presence of anti-brucella antibodies was
studied by the buffered plate agglutination test (BPA), the tube agglutination
test (SAT), the 2-mercaptoethanol (2-ME) agglutination test and indirect ELISA
tests, using the cytosolic fraction from Brucella abortus S19 (CYT), and
lipopolysaccharide (LPS)-free cytosolic proteins (CP). Out of a total of 325
samples analyzed, 17.8% reacted positively to BPA, 13.8% to SAT, 8.0% to 2-ME,
21.0% to ELISA-CYT and 10.0% to ELISA-CP. These results agree with the few data
available in our country and suggest that brucellosis screening should be
extended to other regions.
PMID- 17037255
TI - [Histoplasma capsulatum with aberrant morphology isolated in Argentina].
AB - For the first time in Argentina, we describe a strain of Histoplasma capsulatum
var. capsulatum with an aberrant morphology that was isolated from a single
patient with AIDS. Mycelial phase cultures on agar Sabouraud at 25-28 degrees C
showed white, glabrous, umbilicated and centrally radiated colonies. Unusual
microscopic findings were the absence of typical conidia, the presence of
terminal/intercalary chlamydoconidia with a diameter of 4 pm and of thickened
hyphae. Fungal identification was confirmed by the detection of bands H and M
species specific antigens in mycelial culture supernatants and reversion to the
typical yeast phase on agar brain-heart-cysteine at 37 degrees C. The genomic DNA
profile obtained by RAPD-PCR with primers 1281-1283 coincided with the
predominant profile of H. capsulatum among isolates from Argentine patients.
PMID- 17037256
TI - [Genetic environment of CTX-M-2 in Klebsiella pneumoniae isolates from
hospitalized patients in Uruguay].
AB - We studied two CTX-M-2-producing Klebsiella pneumoniae clinical strains, K96005
and K13, isolated from hospitalized patients in Uruguay, during 1996 and 2003,
respectively. The genomic surroundings of bla(CTX-M-2) were characterized by PCR
mapping and DNA sequencing. Our results show that blaCTX-M-2 is included in a
complex class-1 integron (InK13), associated with an orf513 in both isolates. The
genetic array of the integron, aac(6')-lb, bla(OxA,2), orfD (gene cassette
region), associated with an orf513-bla(CTX-M-2), seems to be widely disseminated
over the Rio de la Plata region.
PMID- 17037257
TI - [Inhibition of Paenibacillus larvae employing a mixture of essential oils and
thymol].
AB - In vitro antimicrobial activity of a mixture of two essential oils and thymol
against Paenibacillus larvae, causal agent of American Foulbrood (AFB), was
evaluated. The essential oils were extracted from cinnamon (Cinnamomum
zeylanicum) and thyme (Thymus vulgaris). The third component used, thymol, is the
major component of the essential oil of thyme which contains 39.9% of thymol.
Minimal inhibitory concentration (MIC) in Mueller-Hinton broth by the tube
dilution method and minimal bactericide concentration (MBC) on MYPGP agar were
evaluated. Thyme registered MIC values of 150-250 microg/ml and MBC values of 200
300 microg/ml, while the MIC and MBC values obtained for cinnamon were of 50-100
microg/ml and 100-125 microg/ml. Thymol showed similar MIC and MBC values of 100
150 microg/ml. No significant differences between the bacterial strains were
detected, but significant differences between essential oils and thymol activity
were registered (P<0,01). An inhibitory synergetic effect on AFB was observed
reducing MIC and MBC values due to the use of a mixture of 62.5% of thyme, 12.5%
of cinnamon and 25% of thymol.
PMID- 17037258
TI - [Moulds and yeasts in bottled water and soft drinks].
AB - Some damaged cartons of soft drinks and carbonated water were analyzed to detect
the microorganisms that caused the damage. The contaminants of sugar used in the
production of one of the drinks were also studied. The methods of Deak & Beuchat
and Pitt & Hocking were used for the identification of yeasts and moulds,
respectively. The agents of the spoilage of soft drinks were Debaryomyces
hansenii, Debaryomyces polymorphus, Galactomyces geotrichum, Metschnikowia
pulcherrima, Mucor circinelloides, Pichia anomala, Pichia jadinii, Pichia
subpelliculosa, Rhodotorula glutinis and Zygosaccharomyces bailii. The
microorganisms found in sugar were Aspergillus niger, Aspergillus penicilloides,
Aspergillus versicolor, Cladosporium sphaerospermum, Mucor racemosus, P. anomala
and Rhizopus stolonifer. Paecilomyces fulvus and Penicillium glabrum were
observed in carbonated water.
PMID- 17037259
TI - [Mechanisms of action of and resistance to rifampicin and isoniazid in
Mycobacterium tuberculosis: new information on old friends].
AB - Human tuberculosis is still one of the most frequent causes of death worldwide.
Despite the implementation of therapeutic regimes combining four drugs, the rise
of resistant and multidrug-resistant Mycobacterium tuberculosis strains has
compromised their efficacy. Two of the most effective anti-tubercular drugs in
use, rifampicin and isoniazid, have been closely studied due to their therapeutic
importance. These studies have led to the identification of the genes involved in
resistance mechanisms and of those encoding the molecular targets for these
drugs. Rifampicin is an inhibitor of the beta-subunit of the RNA polymerase of
prokaryotes, including M. tuberculosis. Resistance to rifampicin is mediated by
mutations clustered in a small region of the rpoB gene. A fraction of resistant
strains showed no mutations in rpoB, suggesting that other mechanisms of
resistance, possibly efflux pumps, may exist. Isoniazid is a pro-drug activated
by KatG, a catalase-peroxidase. Mutations in katG, the most commonly found in M.
tuberculosis clinical isolates, give high levels of resistance. In spite of this,
the molecular target for isoniazid is InhA, an enoyl-ACP-reductase involved in
the biosynthesis of mycolic acids. Other mutations causing resistance to
isoniazid have been mapped to ndh, a gene encoding the NADH dehydrogenase.
PMID- 17037260
TI - Phase I studies of chemotherapeutic agents in cancer patients: a review of the
designs.
AB - I review the designs available for Phase I dose-finding studies of
chemotherapeutic agents in cancer patients. The designs are based on the
assumption that both efficacy and toxicity increase with dose, and thus attempt
to minimize the number of patients treated at low doses, and also to minimize the
chance that patients will be treated at excessively toxic or lethal doses. The
designs fall into two classes: rule-based and model-guided. Rule-based designs
can always determine a reasonable maximum tolerable dose based on observed
toxicity, but when model assumptions are not satisfied, many model-guided designs
will not.
PMID- 17037261
TI - Sequential designs for logistic phase I clinical trials.
AB - Both parametric and nonparametric sequential designs and estimation methods are
implemented in phase I clinical trials. In this article, we take a systematic
approach, consisting of a start-up design, a follow-on design, a sequential dose
finding design, and an estimation method, to find an efficient estimate of the
maximum tolerated dose under the assumption that the dose-response curve has a
true underlying logistic distribution. In particular, for the problem of the
nonexistence of the maximum likelihood estimates of the logistic parameters, a
constraint on the probability of an undetermined maximum likelihood estimator
(MLE) is incorporated into the parametric sequential designs. In addition, this
approach can also be extended to incorporate ethical considerations, which
prohibit an administered dose from exceeding the maximum acceptable dose.
Comparison based on simulation studies between the systematic designs and
nonparametric designs are described both for continuous dose spaces and discrete
dose spaces, respectively.
PMID- 17037262
TI - Adaptive dose selection using efficacy-toxicity trade-offs: illustrations and
practical considerations.
AB - The purpose of this paper is to describe and illustrate an outcome-adaptive
Bayesian procedure, proposed by Thall and Cook (2004), for assigning doses of an
experimental treatment to successive cohorts of patients. The method uses
elicited (efficacy, toxicity) probability pairs to construct a family of trade
off contours that are used to quantify the desirability of each dose. This
provides a basis for determining a best dose for each cohort. The method combines
the goals of conventional Phase I and Phase II trials, and thus may be called a
"Phase I-II" design. We first give a general review of the probability model and
dose-finding algorithm. We next describe an application to a trial of a biologic
agent for treatment of acute myelogenous leukemia, including a computer
simulation study to assess the design's average behavior. To illustrate how the
method may work in practice, we present a cohort-by-cohort example of a
particular trial. We close with a discussion of some practical issues that may
arise during implementation.
PMID- 17037263
TI - Design and analysis of dose-finding studies combining multiple comparisons and
modeling procedures.
AB - The search for an adequate dose involves some of the most complex series of
decisions to be made in developing a clinically viable product. Typically
decisions based on such dose-finding studies reside in two domains: (i) "proof"
of evidence that the treatment is effective and (ii) the need to choose dose(s)
for further development. We consider a unified strategy for designing and
analyzing dose-finding studies, including the testing of proof-of-concept and the
selection of one or more doses to take into further development. The methodology
combines the advantages of multiple comparisons and modeling approaches,
consisting of a multi-stage procedure. Proof-of-concept is tested in the first
stage, using multiple comparison methods to identify statistically significant
contrasts corresponding to a set of candidate models. If proof-of-concept is
established in the first stage, the best model is then used for dose selection in
subsequent stages. This article describes and illustrates practical
considerations related to the implementation of this methodology. We discuss how
to determine sample sizes and perform power calculations based on the proof-of
concept step. A relevant topic in this context is how to obtain good prior values
for the model parameters: different methods to translate prior clinical knowledge
into parameter values are presented and discussed. In addition, different
possibilities of performing sensitivity analyses to assess the consequences of
misspecifying the true parameter values are introduced. All methods are
illustrated by a real dose-response phase II study for an anti-anxiety compound.
PMID- 17037264
TI - Hypothesis testing and Bayesian estimation using a sigmoid Emax model applied to
sparse dose-response designs.
AB - Application of a sigmoid Emax model is described for the assessment of dose
response with designs containing a small number of doses (typically, three to
six). The expanded model is a common Emax model with a power (Hill) parameter
applied to dose and the ED50 parameter. The model will be evaluated following a
strategy proposed by Bretz et al. (2005). The sigmoid Emax model is used to
create several contrasts that have high power to detect an increasing trend from
placebo. Alpha level for the hypothesis of no dose-response is controlled using
multiple comparison methods applied to the p-values obtained from the contrasts.
Subsequent to establishing drug activity, Bayesian methods are used to estimate
the dose-response curve from the sparse dosing design. Bayesian estimation
applied to the sigmoid model represents uncertainty in model selection that is
missed when a single simpler model is selected from a collection of non-nested
models. The goal is to base model selection on substantive knowledge and broad
experience with dose-response relationships rather than criteria selected to
ensure convergence of estimators. Bayesian estimation also addresses deficiencies
in confidence intervals and tests derived from asymptotic-based maximum
likelihood estimation when some parameters are poorly determined, which is
typical for data from common dose-response designs.
PMID- 17037265
TI - Bayesian optimal designs for a quantal dose-response study with potentially
missing observations.
AB - In a dose-response study, there are frequently multiple goals and not all planned
observations are realized at the end of the study. Subjects drop out and the
initial design can be quite different from the final design. Consequently, the
final design can be inefficient. Single- and multiple-objective Bayesian optimal
designs that account for potentially missing observations in quantal response
models were recently proposed in Baek (2005). In this work, we investigate the
efficiencies of the conventional optimal designs that do not incorporate
potential missing information relative to our proposed designs. Furthermore, we
examine the impact of restricted dose range on the resulting optimal designs. As
an application, we used missing data information from a study by Yocum et al.
(2003) to design a study for estimating dose levels of tacrolimus that will
result in a certain percentage of rheumatoid arthritis patients having an ACR20
response at 6 months.
PMID- 17037266
TI - A Bayesian design and analysis for dose-response using informative prior
information.
AB - We wish to use prior information on an existing drug in the design and analysis
of a dose-response study for a new drug candidate within the same pharmacological
class. Using the Bayesian methodology, this prior information can be used
quantitatively and the randomization can be weighted in favor of the new
compound, where there is less information. An Emax model is used to describe the
dose-response of the existing drug. The estimates from this model are used to
provide informative prior information used for the design and analysis of the new
study to establish the relative potency between the new compound and the existing
drug therapy. The assumption is made that the data from previous trials and the
new study are exchangeable. The impact of departures from this assumption can be
quantified through simulations and by assessing the operating characteristics of
various scenarios. Simulations show that relatively modest sample sizes can yield
informative results about the magnitude of the relative potency using this
approach. The operating characteristics are good when assessing model estimates
against clinically important changes in relative potency.
PMID- 17037267
TI - Multiple comparisons and multiple contrasts in randomized dose-response trials-
confidence interval oriented approaches.
AB - According to the ICH E9 recommendation, the evaluation of randomized dose-finding
trials focuses on the graphical presentation of different kinds of simultaneous
confidence intervals: i) superiority of at least one dose vs. placebo with and
without the assumption of order restriction, ii) noninferiority of at least one
dose vs. active control, iii) identification of the minimum effective dose, iv)
identification of the peak dose, v) identification of the maximum safe dose for a
safety endpoint, and vi) estimation of simultaneous confidence intervals for
"many-to-one-by-condition interaction contrasts." Moreover, global tests for a
monotone trend or a trend with a possible downturn effect are discussed. The
basic approach involved obtaining multiple contrasts for different problem
related contrast definitions. For all approaches, definitions of relevance
margins for superiority or noninferiority are needed. Because consensus on
margins only exists for selected therapeutic areas and the definition of absolute
thresholds may be difficult, simultaneous confidence intervals for ratio to
placebo were also used. All approaches are demonstrated in an example-based
manner using the R-packages multcomp (difference), for hypotheses based on
difference, and mratios (ratio), for hypotheses based on ratios.
PMID- 17037268
TI - Using the partitioning principle to adaptively design dose-response studies.
AB - An adaptive two-stage design is proposed for dose-response studies to find the
minimum effective dose. The procedure is conducted in a stepwise fashion based on
the partition testing principle with familywise error rate controlled strongly.
We examine a wide dose range vs. a placebo in the first stage. Then an interim
analysis is conducted with potential modification of design features of the
experiment. Ineffective and/or unsafe dose treatments are terminated, and
selected doses are further investigated in the second stage. Inference is based
on a pre-chosen conditional error function. Several conditional error functions
are discussed and compared.
PMID- 17037269
TI - Fallback tests in dose-response clinical trials.
AB - This article introduces a general testing procedure for performing dose-control
comparisons in dose-response trials with one or more endpoints. The procedure
(termed multi-stage fallback procedure) is an extension of the fallback test
proposed by Wiens (2003). The multi-stage fallback procedure features a simple
stepwise form and improves the power of dose-control tests at higher doses by
taking into account the ordering of the doses. It also serves as an efficient
tool for handling multiplicity caused by multiple endpoints. It is shown in this
article that the multi-stage fallback procedure can be formulated as a closed
testing procedure and thus controls the Type I error rate with respect to
multiple dose-control comparisons as well as multiple endpoints. The proposed
testing method is illustrated using examples from dose-response clinical trials
with single and multiple endpoints.
PMID- 17037270
TI - The grade is: 66 out of 100. Commonwealth gives U.S. healthcare a sickly ranking,
but some say it's time to offer solutions, not point out problems.
AB - When the Commonwealth Fund issued its first scorecard on the U.S. healthcare
system, the news wasn't so great. But the project's authors said the score of 66
points out of 100 shouldn't be interpreted as a failing grade, but a sign the
nation can do much better. The U.S. spends 16% of its GDP on healthcare, said
Karen Davis, president of the Commonwealth Fund. "We are not getting good value
for that investment."
PMID- 17037271
TI - IOM's pay-for-performance fix. Plan would trim all payments, pool money for
rewards.
PMID- 17037272
TI - Calif. Blue Cross fined $200K. Insurer allegedly dropped member to avoid payment.
PMID- 17037273
TI - La. elder-care providers indicted.
PMID- 17037274
TI - The price club. Why a boatload of transparency projects don't have a chance of
reaching shore.
PMID- 17037275
TI - 21st annual Design Awards. With the patient in mind. Simplicity, harmony with
environment distinguish winners..
PMID- 17037276
TI - Quantification of left ventricular regional functions using ECG-gated myocardial
perfusion SPECT--validation of left ventricular systolic functions--.
AB - OBJECTIVE: We have developed a program to quantify regional left ventricular (LV)
function and wall motion synchrony using ECG-gated myocardial perfusion SPECT
(MPS). This preliminary study was undertaken to validate the use of this program
for estimating regional LV systolic function. METHODS: Patients were subjected to
MPS by 99mTc-sestamibi at rest. The study included 20 patients who were confirmed
to have a low probability of coronary artery disease (LPG; low probability
group), 19 heart disease patients who were examined by MPS and equilibrium
radionuclide angiography (ERNA) (ERG; ERNA group), and 24 patients who were
examined by MPS and 2-dimensional echocardiography (2DE) (2DEG; 2DE group). The
values of the ejection fraction (EF) and peak ejection rate (PER) were estimated.
The global functions evaluated by this program were compared with those obtained
by ERNA in the ERG. For regional assessment, the reference values of the
functional indices were obtained for 17 LV segments in LPG. The Z score,
(reference average value of the segment--patient's value of the
segment)/reference standard deviation of the segment, was used for the evaluation
of regional functions; a score equal to or greater than 2 was defined as
abnormal. Semiquantitative visual interpretation of 2DE was used as the standard
to assess wall motion. The sensitivity, specificity, positive predictive value
(PPV), and negative predictive value (NPV) of these criteria and the relationship
between 2DE grading and Z scoring were validated in 2DEG. RESULTS: The values of
the global EF and PER evaluated by this program correlated with those determined
by ERNA (r = 0.76 and 0.58, respectively; p < 0.005 and 0.01, respectively). The
sensitivities of regional EF and PER for segmental wall motion abnormalities were
86.7% and 68.7%, respectively; their specificities were 86.7% and 95.5%,
respectively; their PPVs were 64.3% and 79.2%, respectively; and their NPVs were
96.0% and 91.7%, respectively. The Z scores of these indices significantly
correlated with the scores determined by 2DE (rs = 0.70 and 0.68, respectively; p
< 10(-10)). CONCLUSION: The potential of this program to quantify the regional
systolic function was validated.
PMID- 17037277
TI - The measurement of willingness to pay for mass cancer screening with whole-body
PET (positron emission tomography).
AB - OBJECTIVE: Recently, we have seen an increase in the number of studies that
measured the willingness to pay (WTP) for medical services using the contingent
valuation method (CVM) and evaluated the benefits of these services. This study
aimed to measure the general public's WTP for cancer screening with positron
emission tomography (PET) and to determine consumer characteristics that may
affect their WTP. METHODS: A questionnaire survey of males and females living in
Japan aged between 40 and 59 years was conducted via the Internet. A total of 274
individuals accepted the offer to participate and were enrolled in the study. The
study participants were divided into two groups: Group A (n = 138) and Group B (n
= 136). Group A was provided only with information about the PET procedure and
the high cancer detection rate; Group B was provided with additional information
regarding the possibility of 'false negative' and 'false positive' results and
the fact that the efficacy of PET screening for reducing mortality has not yet
been demonstrated. Participants were then asked to answer their WTP for cancer
screening with PET by paymentcards approach. RESULTS: The overall average amount
consumers were willing to pay for PET cancer screening was dollars 103.7 (n =
274). The average value in Group A was dollars 107.3, the average value in Group
B was dollars 100.0 and there was no statistically significant difference between
the groups. The results of categorical regression analysis showed that household
annual income was the only significant factor affecting WTP. CONCLUSIONS: Our
study showed that household annual income affected the WTP for cancer screening
with PET and therefore the demand for PET screening would be limited to the high
income group. Negative information about PET did not reduce the WTP. This finding
suggests that test subjects mainly evaluated the high detection rate of PET
screening and the 'reassurance' value of receiving negative screening results.
PMID- 17037278
TI - Tumor viability evaluation by positron emission tomography with [18F]FDG in the
liver metastasis rat model.
AB - We prepared a liver metastatic tumor model by injection of rat colon
adenocarcinoma cells to Fischer F344 rats through portal vein, and applied
positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose
([18F]FDG) ([18F]FDG-PET) to this model. At an early stage of the model, multiple
small tumor nodules appeared in the inferior lobes of the livers, and extended
later into the superior lobes. To evaluate the tumor growth and tumor viability
at the early stage, we proposed a new concept, tumor viability index (TVI),
instead of the standardized uptake value (SUV) of the [18F]FDG uptake. The TVI
was defined by subtracting the signal based on the normal liver from the total
signal in the whole liver including tumor nodules: (whole liver SUV-normal liver
SUV) x ml of whole liver region of interest (ROI). For the signal of the whole
liver, ROIs were placed on six slices covering the whole liver, and the ROI of
normal liver region was located in the superior lobe of the liver. The average
TVI values increased with tumor growth and significantly correlated with the
numbers of tumor nodules. The new concept may be useful for evaluating the tumor
viability non-invasively and quantitatively by [18F]FDG-PET.
PMID- 17037279
TI - Contribution of 99mTc-sestamibi infusion SPECT to the characterization of fixed
perfusion defects.
AB - In patients with coronary artery disease, the distinction between scar and viable
myocardium by means of myocardial perfusion imaging (MPI) sometimes can be
difficult because of the equivocal meaning of fixed perfusion defects. In this
study we examined whether addition of a 99mTc-sestamibi infusion study to the
standard MPI could provide extra information regarding the fixed defects. Thirty
seven patients underwent standard MPI and an extra SPECT study in which 99mTc
sestamibi was given as a prolonged constant infusion. Of 324 myocardial segments
available for analysis, 134 had fixed or resting perfusion abnormalities on
standard MPI studies, of which 25% (33/134) in 12 patients showed partial
improvement in the perfusion pattern whereas in 6% (8/134) the improvement was
very significant in infusion studies. In 19 patients who were also examined with
dobutamine echocardiography, 13 showed concordance between echocardiography and
infusion MPI. This study suggests that infusion MPI may provide complementary
information to the conventional scintigraphy with regard to interpretation of
standard myocardial perfusion scans with fixed defects.
PMID- 17037280
TI - New semiquantitative assessment of 123I-FP-CIT by an anatomical standardization
method.
AB - We evaluated a new semiquantitative procedure to more easily and objectively
estimate the striatal uptake of 123I-FP-CIT in patients with Parkinsonian
syndrome (PS) and essential tremor (ET), using an anatomical standardization
method, the Neurostat. METHODS: Eleven patients with PS and 8 with ET were
examined by clinical assessment and 123I-FP-CIT SPECT imaging. The modified Hoehn
and Yahr Staging Scale and Unified Parkinson's Disease Rating Scale (UPDRS) were
used to assess the stage and severity of the disease. The co-registered MR and
SPECT images were created with fusion software included in Neurostat. On the
cross section, which shows the largest area of striate, irregular shaped regions
of interest corresponding to the striate and occipital cortex were drawn. Then
the ratio of specific striatal uptake to non-specific occipital cortex, V3"(F),
was calculated. Another calculation was done by VOIClassic, which is a software
included in Neurostat to estimate the counts per voxel of anatomically defined
regions such as caudate nucleus, putamen, occipital cortex, and total cortex.
Using these count data, the ratio of specific striatal uptake to non-specific
occipital cortex, V3"(OC), and total cortex, V3"(TC), was calculated. RESULTS: A
fair linear correlation was observed between V3"(OC) and V3"(F) (y = 1.53x +
1.40; r = 0.756; p < 0.01), as well as between V3"(TC) and V3"(F) (y = 1.24x +
1.43; r = 0.713; p < 0.01). Both V3"(OC) and V3"(TC) yielded similar tendencies.
Concerning discrimination between ET and PS, there was a significant difference
between the mean V3" of PS and ET (p < 0.01). Concerning the correlation between
V3" value and the severity of PS, the UPDRS motor score significantly correlated
with the V3"(F) value (rs = -0.816). However, V3"(OC) and V3"(TC) correlated less
with UPDRS (rs = -0.667 and -0.645, respectively). CONCLUSIONS: Semiquantitative
parameters, V3"(OC) and V3"(TC), calculated by VOIClassic including the Neurostat
system are useful and easily calculable parameters as well as V3"(F) for the
differential diagnosis of PS from ET.
PMID- 17037281
TI - Fluctuation of adenosine concentration by modes of intravenous infusion based on
mathematical simulation and experiments.
AB - OBJECTIVE: Adenosine, which has been used for a myocardial perfusion scan, shows
rapid clearance from blood because of its short half-life of <10 seconds. This
simulation study evaluates influences of modes of radionuclide injection on
ventricular adenosine concentration when one intravenous injection line is used.
METHODS: Assuming that radionuclide injection is a unit impulse, time-activity
curves were measured in the left ventricle (LV) and fitted by a gamma function.
Typical patterns of concentration fluctuation when adenosine infusion was
temporarily modified were calculated by the convolution integral of input
function and unit impulse response. Variation of concentration was measured by
experiments using continuous 99mTc injection and co-infusion of water via a three
way stopcock. Modes of co-infusion with various infusion speeds and volumes were
examined. RESULTS: Intermission of adenosine infusion and rapid displacement by
radionuclide co-injection significantly influenced the adenosine concentration in
LV. Intermission of adenosine infusion for 2 seconds caused a 15% decrease in the
adenosine concentration in the left ventricle. When a square-shaped input was
assumed, a three-fold higher concentration of adenosine for 3 seconds created by
radionuclide injection resulted in a +42% increase in the LV concentration. Based
on a measured input function, radionuclide injection using three-way stopcock
through one route caused a two- to three-fold increase in the steady
concentration in the vein just after injection. When 0.5 ml of radionuclide was
slowly co-injected, with three ways opened, it caused a relatively low
fluctuation, creating a +34% to -47% change in concentration of LV. A flush of
radionuclide with physiological saline significantly increased the adenosine
concentration in LV, when short half-lives were assumed. CONCLUSION: An
intravenous adenosine and radiopharmaceutical injection in the same line is
feasible. However, the fluctuation of concentration depends significantly on the
mode of injection. To minimize the fluctuation, a slow injection of a small
volume of a myocardial imaging agent via a co-injection route, with three ways
opened, is recommended.
PMID- 17037283
TI - Respiratory distress caused by radioiodine therapy in patients with
differentiated thyroid cancer.
AB - Respiratory distress accompanied by stridor is an uncommon complication of 131I
radioiodine therapy for differentiated thyroid cancer that occurs within 48 hours
of treatment. This report presents three cases with papillary thyroid carcinoma
in which 131I therapy caused this acute complication. One of them had no apparent
risk for this complication such as the existence of remnant thyroid tissue or
laryngeal problems before the treatment. These cases remind physicians that 131I
therapy is not a simple, riskless procedure.
PMID- 17037282
TI - Brain and whole body distribution of N-isopropyl-4-iodoamphetamine (I-123) in
humans: comparison of radiopharmaceuticals marketed by different companies in
Japan.
AB - OBJECTIVE: Iodine-123 (123I)-labeled N-isopropyl-4-iodoamphetamine (IMP) has been
used as a cerebral blood flow (CBF) tracer for single-photon emission computed
tomography (SPECT). An autoradiographic (ARG) method has been developed for the
quantitation of CBF by IMP and SPECT. Two IMPs (IMPA and IMPB) produced by
different radiopharmaceutical companies are marketed in Japan. In the present
study, whole-body distributions including brain and blood of the two IMPs were
compared in the same human subjects. METHODS: Two brain SPECT studies using IMPA
or IMPB were performed on separate days in six young healthy men. Whole-body
scans were also obtained with a large field-of-view single-head gamma camera. One
point arterial blood sampling was performed at 10 min after injection of IMP to
measure both the radioactivity concentrations of whole blood and of octanol
extracted components. RESULTS: No significant differences between the two tracers
were observed in body distribution, tracer kinetics in brain, or regional
distribution in brain. However, the octanol extraction fraction in blood was
significantly different between the two tracers. Radiochemical purity was
slightly but significantly different between the tracers. CONCLUSIONS: In the ARG
method, arterial input function is determined by calibration of a standard input
function with the radioactivity concentration of arterial whole blood. Because
the standard input function in the ARG method was obtained using IMPA, the
standard input function obtained for IMPB should be used when CBF is calculated
by the ARG method with IMPB.
PMID- 17037284
TI - [Disturbances in aggregability of red blood cells in essential hypertension].
AB - The study was performed to find the relationship between rheological properties
of erythrocytes and the effectiveness of antihypertensive therapy both in
patients suffering from essential hypertension as well as in spontaneously
hypertensive rats (SHR). Additionally, in patients receiving the same
antihypertensive therapy we evaluated the effect of aspirin at a low and high
dose on aggregation of erythrocytes. We found that in a consequence of uniformed
antihypertensive therapy which in patients lasted minimum one year and consisted
of one of ACE inhibitors (enalapril or perindopril or captopril), one of beta
antagonists (metoprolol or bisoprolol) and diuretic agent (indapamid), while SHR
lasted 8 days and consisted of ACE inhibitor (chinapril), blood pressure lowered
and red blood cell rheology was significantly improved. For the first time we
observed that antihypertensive treatment which advantageously decreased the
aggregability of erythrocytes was diminished by a high dose of aspirin (300
mg/day).
PMID- 17037285
TI - [Fibrinogen--acute phase protein as a marker of immunological process as
atherosclerosis].
AB - The most important CAD risk factors are: smoking, high level of LDL-cholesterol
and low level of HDL-cholesterol, hypertriglyceridemia, diabetes, obesity,
hypertension, men sex, age over 45 in men and over 55 in women. Carl von
Rokitanski was the first who suggested the role of thrombosis and fibrynolisis in
the development of atherosclerosis and was the author of thrombolic theory. The
recently studies show that atherosclerosis is an immuno-inflamatory process.
Fibrinogen as an acute phase protein is a new marker of ischemic heart disease
and its role in atherosclerosis needs further investigations.
PMID- 17037286
TI - [The functional relevance of Arg16Gly and Gln27Glu-beta2-adrenoreceptor
polymorphism in patients with asthma and allergic rhinitis].
AB - The objective of the present study was to investigate the effect of beta2
adrenoreceptor polymorphisms Arg16Gly and Gln27Glu as well as their relationship
to the pulmonary function parameters, and the clinical presentation in patients
with asthma and allergic rhinitis. Investigated polymorphisms were in linkage
disequilibrium, therefore their effects should be evaluated collectively.
Although no significant association could be found with the presence of asthma or
allergic rhinitis in studied population, polymorphisms of beta2-adrenoreceptor
can influence pulmonary function in these patients. These effects significantly
differ between men and women, possibly indicating the effect of sex hormones on
genetic regulation of pulmonary function.
PMID- 17037287
TI - 24-hour heart rate variability in patients with gastroesophageal reflux disease.
AB - The GERD pathogenesis may be associated with disturbances of the autonomic
nervous system (ANS), which can be revealed using heart rate variability studies
(HRV). The aim of presented study was to estimate the circadian ANS activity in
24-hour HRV recordings in GERD patients, both in non-erosive form (NERD), and
with erosive, inflammatory changes in the esophagus (ERD patients). Our results
demonstrated disturbances in the parasympathetic ANS part, but they also
delivered the proofs for possible sympathetic disorder. That is why the autonomic
neuropathy in GERD patients may have mixed character.
PMID- 17037288
TI - [Motor and endocrine function disturbances of the gastrointestinal tract in
patients with chronic renal failure (CRF)].
AB - In the chronic renal failure (CRF) there are several upper gastrointestinal
symptoms, which result from both disturbed motor function (associated with the
delayed gastric emptying) and myoelectrical one (associated with abnormal
electrogastrography registration). In patients suffering from CRF, disturbances
of the endocrine digestive system function were also demonstrated, which are
related to the observations of many gastrointestinal hormones increased levels.
PMID- 17037289
TI - Mechanisms of intestinal dysmotility in morphine dependence: whether central or
peripheral?
AB - Changes of intestinal motility and transit due to morphine administration are
attributed to its central and peripheral action, however coexistence of both
central and peripheral mu receptors in morphine dependence hasn't been clearly
demonstrated so far. Our purpose was the evaluation of the effect of either CNS
or ENS mu receptor blockade on intestinal motility in morphine dependent rats.
Twenty male rats were subjected to chronic subcutaneous morphine infusions for 72
hrs. On each day motility indices (MI) were analysed in the animals' duodenum and
ascending colon before and after either intraperitoneal (IP) or
intracerebroventricular (ICV) mu antagonist (CTOP) administration. Tolerance of
the intestinal motility to morphine developed in both the duodenum and the
ascending colon after 72 hrs of the infusion. Dependence was observed at 24 hrs
and maintained at 48 and 72 hrs of morphine administration. On each day no
differences of MI reaction to mu blockade were visible regarding the IP or ICV
CTOP administration. Our results suggest the involvement of both the CNS and the
ENS mu opioid receptors in mechanisms of the intestinal tolerance to and
dependence upon morphine.
PMID- 17037290
TI - [Gastric myoelectrical dysfunction in patients with hematoma of the posterior
cranial fossa].
AB - Demonstrated disturbances of gastric myoelectrical activity in 10 patients with
hematoma of the posterior cranial fossa. Tachygastria amounts 40% of the
recording time.
PMID- 17037291
TI - [Preoperative diagnostics in patients with adrenal tumors].
AB - The aim of the study was analysis of preoperative diagnostics of patients who
underwent laparoscopic adrenalectomy. In the preoperative diagnostics in 10
patients (22.2%) pheochromocytoma was found, in 8 (17.8%) Conn's syndrome, in 4
(8.9%) Cushing's syndrome and in 1 (2.2%) adrenal virilization. Full accordance
between histopathological findings and preoperative diagnosis was achieved in 91%
of cases. Four cases of discrepancy were: 1 false positive preoperative diagnosis
of aldosteronoma, 1 false positive and 2 false negative diagnosis of
pheochromocytoma.
PMID- 17037292
TI - [Dextromethorphan enhances analgesic activity of propacetamol--experimental
study].
AB - While many pre-clinical and clinical studies have suggested that the addition of
N-methyl-d--aspartate (NMDA) receptor antagonists, such as dextromethorphan, to
opioid analgesics, such as morphine may enhance the analgesic effects. The aim of
the study was to assess the effect of non-competitive NMDA antagonists and
paracetamol (propacetamol) on pain threshold and analgesic potency of this drugs
and their combinations in formalin model for pain in rats. Intraperitoneal
administration of paracetamol only in doses of 100 g/kg or higher resulted in
increase of pain threshold in tail flick and paw pressure tests. The results of
our study suggest that there was no significant difference in pain threshold
between separate administration of dextromethorphan and in combination with
paracetamol. In a formalin model for pain we have shown that paracetamol in non
analgesic doses (10 mg/kg) administered in combination with dextrometorphan,
ketamine and mamantine was more effective than those drugs given separately but
the best analgesic effect was obtained when combination of paracetamol and
dextromethorphan was applied. The addition of higher doses of these combined
drugs, that is paracetamol and all three NMDA antagonists did not result in
enhancement of dose-dependant analgesia. In conclusion it should be stated that
NMDA antagonists improve analgesic effect of paracetamol in the formalin model
for pain. although only to a limited extend.
PMID- 17037294
TI - [Internal medicine leading the revolution in medical care].
PMID- 17037293
TI - [The influence of soybean riches of phytoestrogens diet in mouse testis
histological structure].
AB - Soybean diet, a rich source of phytoestrogenes, affects negatively on the
potential fecundity in male mice. It causes spermatogenesis impairment which is
manifested by changes in testicular histology. Germ epithelium becomes darker and
sheds and a number of produced spermatozoa decreases. On the other hand a number
of testicular macrophages significantly rises in Leydig glands.
PMID- 17037295
TI - [Tasks in medical care in Japan and the world].
PMID- 17037297
TI - [Scope of family doctor activity in Japan].
PMID- 17037296
TI - [Knowledge of psychiatry necessary in primary care].
PMID- 17037298
TI - [Liver regeneration with stem cell transplantation and its clinical application].
PMID- 17037299
TI - [High risk pathophysiology and the molecular mechanism of arteriosclerosis].
PMID- 17037300
TI - [Front line of molecular biological study on and therapy for pulmonary
hypertension].
PMID- 17037301
TI - [Function of language area in the brain].
PMID- 17037302
TI - [New developments in therapeutics for infectious diseases].
PMID- 17037303
TI - [Metabolic syndrome].
PMID- 17037304
TI - [Metabolic syndrome and insulin resistance].
PMID- 17037305
TI - [Metabolic syndrome and lipotoxicity].
PMID- 17037306
TI - [Metabolic syndrome and aldosterone].
PMID- 17037307
TI - [Diagnosis of metabolic syndrome].
PMID- 17037309
TI - [Cerebrovascular diseases and RAS].
PMID- 17037308
TI - [Therapy for metabolic syndrome].
PMID- 17037310
TI - [Clinical significance of RAS block in heart diseases].
PMID- 17037311
TI - [Kidney disease and RAS].
PMID- 17037312
TI - [Pathophysiological significance of RAS in formation of arteriosclerosis].
PMID- 17037313
TI - [Renin-angiotensin system and insulin resistance: carbohydrate-metabolism
disorders].
PMID- 17037314
TI - [Leukocytapheresis for inflammatory immune diseases].
PMID- 17037315
TI - [Cytokine targetting therapy for inflammatory bowel diseases].
PMID- 17037316
TI - [TNF targetting therapy for rheumatoid arthritis].
PMID- 17037317
TI - [IL-6 targetting therapy for inflammatory immune diseases].
PMID- 17037318
TI - [Anti-CD20 antibody therapy for inflammatory immune diseases].
PMID- 17037319
TI - [Safety issues in medical care: For whom the care belongs?].
PMID- 17037320
TI - [Safety issues in medical care: next step toward the safety standard].
PMID- 17037321
TI - [Safety issues in medical care: present condition of medical safety management in
hospitals].
PMID- 17037322
TI - [ Safety issues in medical care: aiming for the safe culture].
PMID- 17037323
TI - [Safety measures for medical care in Japan].
PMID- 17037324
TI - [Physiopathology of lipoprotein glomerulopathy].
PMID- 17037325
TI - [Progress in AIDS therapy].
PMID- 17037326
TI - [Physiopathology of and therapy for aplastic anemia].
PMID- 17037327
TI - [Clinical significance of KL-6].
PMID- 17037328
TI - [Liver transplantation for familial amyloidosis].
PMID- 17037329
TI - [Inflammation and oxidative stress].
PMID- 17037330
TI - [Diagnosis of and therapy for nonalcoholic steatohepatitis].
PMID- 17037331
TI - [Pathophysiology of and therapy for mixed connective tissue disease: recent
progress on the study].
PMID- 17037332
TI - [Recent progress in insulin therapy].
PMID- 17037333
TI - [Future prospects for botulinum toxin therapy].
PMID- 17037334
TI - [Physiopathology of and therapy for diabetic nephropathies].
PMID- 17037335
TI - [Chronic hypersensitivity pneumonitis].
PMID- 17037336
TI - [Present status and future prospects in non-drug therapy for arrhythmia].
PMID- 17037337
TI - [Recent progress in diagnosis of and therapy for multiple myeloma].
PMID- 17037338
TI - [Medical care for hyperlipidemia].
PMID- 17037339
TI - [Etiology of and therapy for gastrointestinal stromal tumor].
PMID- 17037340
TI - [Controlling hospital infections and the cost effectiveness].
PMID- 17037341
TI - [CT diagnosis of coronary artery diseases].
PMID- 17037342
TI - [Hepatectomy and perisurgical management for heavy drinker with hepatocellular
carcinoma].
AB - Hepatic resection is the first choice of treatment for hepatocellular carcinoma
(HCC), and has the best results among the therapeutic options. Preoperative
evaluation of liver function in patients and perioperative management for
patients, to prevent postoperative complications, are very important.
Postoperative pulmonary complications, including pneumonia and atelectasis, were
frequently shown in patients who had past history of heavy alcohol-intake.
Postoperative pulmonary complications in heavy drinkers were associated with
their habit of smoking. Temperance and non-smoking should be required, when
hepatectomy will be performed for heavy drinker.
PMID- 17037343
TI - [How do self-help agencies work for recovery of drug dependence in Japan?].
AB - DARC (Drug Addiction Rehabilitation Center) is the first and largest private half
way house agency for drug addiction in Japan, in which the programs are centered
on 12 step meetings and the staff is made up of only those recovered from drug
dependence. The purpose of this report is to elucidate how DARC works in the
recovery from drug dependence. We made two studies: staff in 30 DARC facilities
and 108 users in 7 male residential facilities. The results showed that 330
clients with drug dependence were participating in DARC programs at the time of
research and about 600 clients use the programs each year. According to our
research, three fourths of the users could maintain sobriety. Although many users
had severe mental symptoms and socioeconomic difficulties, most users evaluated
DARC programs highly to help them recover from these conditions. DARC rated
highly because it provides companionship for recovered addicts and flexible
frameworks to enhance drug addicts' motivation to recover, such as accepting
dropouts and restarting programs, the provision of facilities away from areas
where users were at high risk of relapse, and various program modalities.
PMID- 17037344
TI - [Alcohol dependence syndrome and Before-Discharge Intervention Method (BDIM)--No.
5. Patients' evaluation of BDIM by questionnaire survey].
AB - One (A.I) of the authors has developed BDIM (Before-Discharge Intervention
Method) for the purpose of making alcoholics aware of their drinking problems.
153 patients were treated by BDIM. After the practiced BDIM, the patients
underwent a 52 month observational period. 82 patients (53.6%) continued with
either treatment as outpatient or inpatients, or attendance of a self-help group.
We administered these 82 patients our questionnaire that asked for their
assessment about the therapeutic effects of BDIM. 76 patients (49.7%) completed
our questionnaire. Regarding the impression of family members' letters in BDIM,
70 patients (92.1% of 76) answered that the letter have had a positive impression
on them. 52 patients (68.4% of 76) answered that they have had very strong or
strong impressions. The numbers of patients who have [very strong or strong]
impression are significantly more in the abstinence group than in the drinking
group. Also, we asked patients about which messages of spouses, daughters and
sons in BDIM gave the strongest impression to these patients. The result showed
that their daughter gave the strongest impression to many patients. We believe
that their children, especially the patients' daughter's messages, have
therapeutic effects as impact messages even though alcoholics have cognitive or
memory disorder. Patients positively assessed that BDIM strengthened motivation
for treatment or attendance of self-help group meetings, for abstinence and for
the consequence to their lives. Many patients assessed that BDIM has effect on
awareness of their drinking problems. But the ratio of positive answers about
motivation of awareness of drinking problem is smaller than the ratio of positive
answers about other questions. As a result, we surmised that BDIM will have the
effect of empowerment, including the effect of awareness.
PMID- 17037345
TI - Reliability and validity of the Japanese version of the Addiction Severity Index
(ASI-J).
AB - The Addiction Severity Index (ASI) is a frequently used clinical and research
instrument that collects data from substance abusers in seven problem areas:
medical, employment, alcohol, drug use, legal, family-social functioning, and
psychiatric status. In each area, the ASI provides a composite score and severity
rating that estimate the seriousness of the problem and the client's need for
treatment. In the present study, we investigated the reliability and validity of
the Japanese version of the ASI (ASI-J). One hundred and eleven subjects with a
history of drug abuse were interviewed with a test battery including the ASI with
informed consent. This revealed that: (a) the problem areas were independent of
each other, underscoring the need for multidimensional assessment, (b) the inter
rater correlation of severity ratings in each area ranged from 0.68 to 0.99, and
Cronbach's alpha coefficient for the items used for the composite score in each
area ranged from 0.57 to 0.86, indicating their reliability with the exception of
the drug and employment areas, and (c) several composite scores were
significantly correlated with the drug craving levels assessed by a visual
analogue scale, the abstinence period, mental health, and/or relapse, supporting
their concurrent and predictive validity. These results suggest that the ASI-J
has acceptable reliability and validity.
PMID- 17037346
TI - [The relationship between smoking behavior in young people and CYP2A6 gene
polymorphisms, between them and personality traits assessed by NEO-FFI].
AB - We performed a survey on nicotine dependence among young students. We examined
the CYP2A6 gene polymorphism using PCR-RFLP. We examined the personality traits
using NEO-FFI. Samples were taken from young students of which 87 were smokers
and 142 were non-smokers and we tried to clarify the relationship between the
nicotine metabolizing ability (CYP2A6), personality, and smoking behavior. As a
result, the frequency of the CYP2A6*4C gene was significantly higher among non
smokers than smokers, and the Openness score by NEO-FFI was higher among smokers
than non-smokers. We concluded that the CYP2A6*4C gene and the Openness
personality trait may be a cause of smoking among the young smokers. Therefore,
there is a possibility that smoking behavior in youths may be affected not only
by the CYP2A6 gene but also by the Openness personality trait.
PMID- 17037347
TI - [Classification and virion structure of influenza virus].
PMID- 17037348
TI - [History of influenza virus research].
AB - I divided the history of influenza virus research into four groups according to
the development of analysis methods. Since isolation of human influenza virus in
1933, many works have been done. However, under the limitation of analysis
method, progress in knowledge about influenza virus was very slow and many
questions remained until the molecular biological methods were developed. After
1975, by using molecular biological methods, influenza virus research progressed
rapidly. Especially, by the application of PCR method, followed by capillary
autosequencer, the research of influenza virus genome developed rapidly. Now, we
can handle the influenza virus by manipulation of cloned cDNAs by reverse
genetics.
PMID- 17037349
TI - [Pandemic influenza measures in Japan--from the point of government].
AB - H5N1 type avian flu infection has spread among poultry starting from Vietnam to
southwest region countries since the end of 2003. Afterwards, the infections have
expanded through Africa, Europe and even to worldwide. Cases of H5N1 type avian
flu virus infections to human are increasing. So, the risk of acquiring, through
mutation, capacity of human-to-human spread would be higher. As human has not
been infected by such virus, it is worried that a pandemic, and even the increase
of deaths due to this virus could be occurred. Japan produced "Pandemic Influenza
Preparedness Action Plan" last year, and also takes genuine measures against a
new pathogenic avian influenza virus. Various countries, including Japan, are
trying to find positive measures towards it, although it has not been found.
PMID- 17037350
TI - [Influenza surveillance in Japan].
AB - In Japan, under the National Epidemiological Surveillance of Infectious Diseases,
clinically diagnosed influenza cases have been reported by approximately 5,000
influenza sentinel clinics and influenza virus isolation have been reported by
prefectural and municipal public health institutes (PHIs). Influenza virus strain
surveillance have been conducted by PHIs and National Institute of Infectious
Diseases for selectin of vaccine strains. Weekly influenza case and influenza
virus isolation data have been submitted to WHO FluNet website. In addition, HI
antibody prevalence have been monitored by the National Epidemiological
Surveillance of Vaccine-preventable Diseases. Various information about influenza
surveillance in Japan is available on the Infectious Disease Surveillance Center
website (http://idsc.nih.go.jp/iasr/index.html).
PMID- 17037351
TI - [Gene expression of influenza viruses during replication].
AB - Both transcription and replication of influenza virus genome take place in the
nucleus of the infected cells. Initiation of mRNA synthesis requires the
generation of capped primers cleaved from the 5' end of the host pre-mRNA by a
cap-snatching mechanism. These transcripts are polyadenylated at their 3' ends
when the viral polymerase stutters over a polyuridine stretch that is found 15-22
nucleotides from the 5' end of the vRNA. Replication of the viral genome is
achieved through primer-independent synthesis of a full-length, positive-sense
replicative intermediate, cRNA, that is copied into vRNA. The switch from mRNA to
template RNA(cRNA) synthesis requires antitermination activity of NP proteins not
associated with nucleocapsids. M gene expression differs among influenza A, B and
C viruses.
PMID- 17037352
TI - [Review on replication cycle of influenza virus].
AB - Influenza virus belongs to Orthomyxoviridae, which replicates its genome in
nuclei of host cells. Replication requires binding to the cellular receptor,
entry into host cytoplasm and other several steps followed. In this article,
recent findings of the virus replication steps, particularly emphasized on
receptor recognition, fusion process, RNP transport and assembly were reviewed.
PMID- 17037353
TI - [Defense mechanism against respiratory infection].
AB - Most of acute respiratory diseases are caused by infection with various viruses,
bacteria and other microorganisms; a mixed infection with these pathogens often
results in exacerbation of the disease. In addition to nonspecific protective
mechanisms that constantly function in the respiratory tracts, innate and
adaptive immunities play important roles in the protection of these pathogens.
Secretory IgA and/or cytotoxic T cells in the mucus may be the most effective
protection machineries of the adaptive immune systems. Recently, it has been
proven that Toll-like receptors, each of which recognizes a conserved structure
of pathogens, are the key molecules of the innate immune systems; this
recognition step is considered a prerequisite for the adaptive immunity to
function in the respiratory tracts.
PMID- 17037354
TI - [Expression of host genes in influenza virus infected cells].
AB - When NCI-H292 human bronchial epithelial cells were infected with influenza
A/Udorn/72(H3N2) virus, 152 host genes were identified as virus-stimulated genes
(VSGs). The expression of these genes was increased more than 4-fold by the virus
infection and reached to the level of more than one copy per cell. Seventy-three
VSGs were also stimulated by interferon-beta (IFN-beta) treatment and they
contained the genes known to possess antiviral activity. As a likely consequence,
the production of progeny viruses was transient in H292 cells and the cells
survived through infection. The stimulation of the VSGs is not mediated by IFNs
but triggered by the infection itself at least at the early phase of infection.
In A549 human lung epithelial cells, the increase of the VSG expression was less
than 1/6 on the average of that in H292 and virus production continued until cell
death. These indicate that some VSGs might constitute intracellular antiviral
mechanisms. On the other hand, the NS1 protein of influenza virus shuts off host
gene expression by inhibiting the polyadenylation-site cleavage of host pre
mRNAs. Therefore, balance of the shut-off and the activation of cellular genes
during virus infection may be crucial in determining the outcome of infection.
PMID- 17037355
TI - [Cytokines and chemokines induced by influenza virus infection].
AB - Many kinds of cytokines and chemokines are produced in response to influenza
virus infection through the course of cytokine cascade. Even a single cytokine
exhibits various biological activities and different types of cells produce the
same identical cytokine. In general, cytokines act to maintain the homeostasis of
host condition. In influenza virus infection, it works as protective for the host
against virus infection at its early stage, but often as pathogenic in its later
stage. Cytokines play a pivotal role in establishment of virus specific immunity.
However, over expression of cytokines causes irreversible severe damages to the
host, including shock, disseminated intravascular coagulation, adult respiratory
distress syndrome and multiple organ failure, a typical form of which is
influenza encephalopathy. Pathogenicity of influenza virus might be determined by
means of its potential capability to induce proinflammatory cytokines.
PMID- 17037356
TI - [The laboratory diagnosis of influenza viruses].
AB - The methods of the pathogen diagnosis for confirm the infection of the influenza
virus, there are the viral isolation and the method of detected the viral
antigen. In the each method of inspection, the time of sample extraction, the
method of extraction and preservation must be suited to fully improve the
sensitivity and specificity. The viral isolation is necessary and indispensable
to analyze the antigen of the epidemic viruses and it is the high level of
sensitivity. The several methods of detecting the antigen of the gene
amplification include the reverse transcription polymerase chain reaction (RT
PCR) method, the loop-mediated isothermal amplification (LAMP) method, the real
time PCR method, and the nucleic acid sequence-based amplification (NASBA)
method, and these methods are excellent promptly. As for these detection methods,
being chosen according to the purpose is desirable.
PMID- 17037357
TI - [Rapid diagnostic kits using immunochromatography for detection of influenza
viruses].
AB - The development of rapid diagnostic kits using immunochromatography has made it
possible to definitively diagnose influenza A and B simply and quickly in
outpatient services. I have studied these kits using nasopharyngeal aspirates
from children as samples. With the most superior kit, the sensitivity to
influenza A viruses was almost 100%, and that to influenza B viruses was 90%.
PMID- 17037358
TI - [Treatment of influenza virus infection with anti-virals].
AB - Dramatic advances have been made in the diagnosis and treatment of influenza in
Japan in recent years. Most patients with influenza-like illness are now tested
with rapid diagnostic tests, and if the results are positive, they are treated
with neuraminidase inhibitors, mostly oseltamivir. However, we experienced
emergence of resistant strains to oseltamivir and variable side effects.
Zanamivir will be used widely in Japan, because it is characterized of lower rate
of resistance. Stockpiling of those antivirals is essential for pandemic
preparedness plan.
PMID- 17037359
TI - [The molecular basis of resistance to anti-influenza drugs].
AB - Influenza A viruses resistant to adamantanes(amantadine and rimantadine) have
drastically increased in the last few years. Moreover, these adamantane-resistant
viruses have acquired resistance without compromising viral pathogenicity and
transmissibility. Viruses resistant to the other anti-influenza drugs,
neuraminidase (NA) inhibitors, have also been shown to emerge at a rate higher
than previously thought. In addition, several recent observations suggest that
human-to-human transmission of variants resistant to NA inhibitors may have
occurred, contrary to earlier predictions that such variants were much less
likely to be transmitted. Although the prevalence of NA inhibitor resistants
remains low, surveillance of drug-resistant influenza viruses in communities is
essential. Here, we review antiviral resistance in influenza viruses and the
molecular mechanisms of the acquisition of resistance to these drugs.
PMID- 17037360
TI - [Development of attenuated H5N1 avian influenza vaccines using reverse genetic
technology].
AB - Outbreaks caused by highly pathogenic H5N1 avian influenza viruses have spread
worldwide and the containment is impossible no longer. During the outbreaks, over
200 human infection cases with 55% fatality are confirmed at the moment and some
human-to -human transmission in family clusters have been observed in Vietnam,
Thailand and Indonesia. The potency of pandemic caused by highly pathogenic H5N1
avian influenza is increasing gradually. Consequently, development of effective
H5N1 vaccine and its licensing for vaccination to human are urgent
countermeasures for pandemic preparedness. In the present article, the author
reviews the development of H5N1 attenuated vaccine by reverse genetic technology
and discuss the problems on the vaccine production to be dissolved before
pandemic occur.
PMID- 17037361
TI - [DNA vaccination].
AB - No one knows the timing when influenza pandemic will occur, but that catastrophe
will undoubtedly happen. Current vaccines elicit antibodies to membranes of
viruses effective against highly specific strains, however they are not effective
against multiple strains. New strategies are urgently needed for the protection
against multiple strains. It is necessary to develop immunologically superior
vaccines. DNA vaccination is an established immunization method in animal models.
DNA vaccines are gaining importance due to the induction of a strong cellular
immunity. Moreover, the protection against multiple strains of influenza A virus
has already been achieved. But their immunogenicity is not so strong that to
improve the efficacy of this method is very important. This article highlights
some of the recent developments in investigational DNA vaccines. Various tactics
for enhancement of their immunity are considered. DNA vaccines together with DNA
encoding various cytokines showed better immunological responses in several
animal models. Alteration in the vector, inclusion of CpG-ODN motifs, addition of
transcriptional factor and appropriate vaccine delivery mechanisms are expected
to further improve the efficacy of these vaccines.
PMID- 17037362
TI - [Intranasal inactivated influenza vaccine].
AB - Natural influenza virus infection is well known to be superior to parenteral
inactivated vaccines, which induce serum IgG antibodies(Abs) alone, in inducing
the broad-spectrum cross-protection against variant virus infection. Secretory
IgA Abs, which provide cross-protection strongly against infection with variant
viruses within the same subtype mainly in the upper respiratory tract, serum IgG
Abs, which provide cross-protection weakly against infection with variant viruses
mainly in the lower respiratory tract, and cytotoxic T lymphocytes, which provide
cross-protection against infection with different subtype viruses and whose role
is not always big in humans, are involved in the defence mechanisms induced by
natural infection. The development of intranasal inactivated vaccine, capable of
inducing both IgA and IgG Abs, is important to improve the efficacy of current
inactivated vaccine.
PMID- 17037363
TI - [Analysis of SNPs and enzymatic disorder in the patients of influenza-associated
encephalopathy: disorder of fatty acid metabolism in mitochondria induced by high
fever].
AB - To assess the etiology of influenza-associated encephalopathy(IAE), a
surveillance effort was conducted during 2000-2005 in Japan. Over half of fatal
and handicapped IAE patients exhibited a disorder of mitochondrial beta-oxidation
and ATP generation evoked by the thermolabile phenotype of carnitine
palmitoyltransferase II variations with transiently elevated serum acylcarnitine
during high-grade fever. Model mice having impaired mitochondrial beta-oxidation
exhibited significant accumulation of mini-plasmin and up-regulation of trypsin
in the cerebral capillaries after infection with influenza A virus, resulting in
the destruction of blood-brain barrier and increased brain vascular permeability.
Trypsin up-regulation was also evident in the neuronal cells in the hippocampus,
suggesting a severe neurologic complication of IAE.
PMID- 17037365
TI - [Guideline for the management of influenza associated encephalopathy].
PMID- 17037364
TI - [Neuroradiological findings in the acute stage of influenza encephalopathy].
AB - Influenza encephalopathy(IE) is characterized by its high incidence in Japanese
children between 1 year and 5 years of age, its onset in the first or the second
day of illness and its high mortality (15-30%) and morbidity (25-40%). We
proposed the classification of IE with poor prognosis from the neuroradiological
findings. Four types of encephalopathy seem to be differentiated from each other,
1. acute necrotising encephalopathy(ANE) type, 2. hemorrhagic shock and
encephalopathy syndrome (HSES) type, 3. acute brain swelling(ABS) type, 4. acute
encephalopathy with febrile convulsive status epilepticus (AEFCSE) type. The
notable radiological features are thalamic lesions in ANE, diffuse cerebral
cortical cytotoxic edema in HSES, reversible cerebral swelling in ABS which
sometimes reaches lethal brain herniation, and localised cerebral edema which is
called as "lobar edema" because its extent seems to be equivalent to cerebral
lobes. "Lobar edema" is developed about four days after status epilepticus
simultaneously with the onset of repetitious focal seizure and neurological
deterioration. The radiological changes in the early phase of IE are described in
each types. In conclusion IE is a constellation of different types of
encephalopathy although a further research of encephalopathy is urgently needed.
PMID- 17037366
TI - [Pneumonia associated with influenza virus infection].
AB - The history of influenza pandemics was reviewed and clinical manifestations of
pneumonia associated with influenza virus infections are described and several
typical cases are presented. Several types of pneumonia associated with the
influenza virus infection have been reported: 1) influenza complicated by
secondary bacterial pneumonia, 2) primary influenza virus pneumonia, 3) combined
influenza virus and bacterial pneumonia. Secondary bacterial pneumonia often
produces a syndrome that is clinically distinguishable from that of primary viral
pneumonia. In primary influenza virus pneumonia, chest roentgenography revealed
bilateral infiltrations but no consolidation. Histologically, diffuse alveolar
damage and hemorrhagic bronchiolitis were frequently observed in primary
influenza virus pneumonia, in which case the prognosis was the worst. Although
rare, the possibility of cryptogenic organizing pneumonia associated with
influenza virus infection should be recognized. H. influenzae, S. pneumoniae, or
S. aureus were frequently associated with influenza viral infection, and
treatment against these bacteria should be considered.
PMID- 17037367
TI - [Influenza myocarditis and pericarditis].
AB - The true incidence of influenza myocarditis in the general population is unknown,
because of the variable clinical presentation and the absence of a established
noninvasive diagnostic test that can confirm the diagnosis. Influenza is,
however, one of the frequently implicated viruses caused myocarditis as well as
Coxsackie B, adenovirus, echovirus and cytomegalovirus. The clinical
manifestations of viral myocarditis vary greatly from asymptomatic
electrocardiographic changes to fulminant heart failure with fatal arrhythmias.
We should recognize that subtle cardiac symptoms and signs in many subclinical
cases may be overshadowed by systemic manifestations of the underlying influenza
infection. Although specific therapy consisted of anti-viral agents, intravenous
gamma-globulin treatment or mechanical ventricular supports may be available for
influenza myocarditis, it has not been established that the myocarditic process
itself will be favorably affected.
PMID- 17037368
TI - [Acute myositis associated with influenza].
AB - Benign acute myositis associated with influenza is reported from all over the
world. The characteristics of this disorder is calf pain and difficulty walking
during a viral illness (3-8 days) and creatine kinase levels are mildly or
moderately elevated. Recovery occurred within 1 week. Midchildhood (mean age: 6-8
years) is most commonly affected and boys are more commonly than girls and its
ratio is 2.4 : 1 by Shimizu in Japan (1993). Elderly patients are also reported.
Viral studies show that influenza B is more commonly than influenza A and the
ratio is 6 : 1 by Hu in Taiwan (2004), 2.4 : 1 by Shimizu in Japan (1993). Muscle
histology revealed isolated segmental muscle degeneration and necrosis without
frank myositis. A direct role of influenza virus in its genesis is not clear. An
age-related response and occurrence primarily on boys may reflect a genetic
predisposition.
PMID- 17037369
TI - [Influenza in the patient of chronic respiratory disease].
AB - The patient of chronic respiratory disease belongs to high risk group of the
influenza, and when influenza will happen, they will become sever. Therefore,
these patient should take the vaccination at first. Being vaccinated, even if the
influenza will occur, the condition will not be sever and with the antiviral
agents, anti-bacterial agents should be given with or without the existence of
bacterial infection.
PMID- 17037370
TI - [Influenza complicating pregnancy].
AB - Influenza is a highly contagious acute respiratory infection that is of major
clinical importance both in Japan and worldwide. This infection usually is not
life-threatening in otherwise healthy adults, but pregnant women do not tolerate
serious pulmonary involvement. In previous reports of influenza pandemics,
pregnant women have experienced increased risk of morbidity and mortality
compared to non-pregnant women. In addition, mothers with severe respiratory
infections may have an increased risk of preterm labor. Vaccination against
influenza is recommended for all women who will be pregnant during the influenza
season to prevent the occurrence of influenza and the development of pneumonia.
There is no firm evidence that maternal infection is associated with an increased
risk of spontaneous abortion, stillbirth, or congenital anomalies. However, an
infant delivered to an acutely infected patient may develop neonatal influenza as
a result of close personal contact with its mother.
PMID- 17037371
TI - [Highly pathogenic avian influenza--monitoring of migratory waterfowl].
AB - Since 1979, the group belonging to Departments of Veterinary Microbiology,
Veterinary Public Health and the Avian Zoonoses Research Centre, Faculty of
Agriculture, Tottori University is continuing isolation of avian influenza virus
from such migratory waterfowls as whistling swan, pintail and tufted dugs flying
from Siberia and/or northern China. They have already isolated many interesting
influenza viruses. Serotype of the isolates is various; some H5 and H7 and human
types of viruses were also isolated; and its pathogenicity for chickens is not
high. It was interested that low pathogenic H5N3 virus isolated from whistling
swan acquired severe pathogenicity during passage in chicks.
PMID- 17037372
TI - [Type C influenza].
AB - The influenza C virus genome consists of seven single-stranded RNA segments of
negative polarity. The hemagglutinin-esterase (HE) glycoprotein of influenza C
virus has three biological activities, i.e. receptor-binding activity for N
acetyl-9-O-acetylneuraminic acid, fusion activity, and receptor-destroying
activity, which is a neuraminate-O-acetylesterase. Unspliced mRNA from RNA
segment 6 is first translated into a 374-amino-acid protein, P42. P42 is cleaved
by signal peptidase, producing M1' and CM2 proteins, composed of the N-terminal
259 amino acids and the C-terminal 115 amino acids, respectively. Xenopus laevis
oocytes expressing influenza C virus CM2 protein demonstrated that CM2 protein
forms a voltage-activated ion channel permeable to chloride ion.
PMID- 17037373
TI - [Global influenza surveillance].
AB - Global influenza surveillance is run by WHO Global Influenza Programme in
collaboration with WHO Global Influenza Surveillance Network. Network partners
collect specimens in their countries, perform primary virus isolation and
preliminary antigenic characterization. They ship newly isolated strains to WHO
Collaboration Centers for high level antigenic and genetic analysis, the result
of which forms the basis for WHO recommendations on the composition of influenza
vaccine for the Northern and Southern Hemisphere each year. The WHO Influenza
Surveillance Network serves also as a global alert mechanism for the emergence of
influenza viruses with pandemic potential.
PMID- 17037374
TI - [Regulation of adipose functions by molecular clocks].
AB - Adipocytes play essential metabolic roles, not only serving as massive energy
reserves but also secreting hormones and cytokines that regulate metabolic
activities. The link between metabolic activity in adipocytes and circadian
rhythm has long been studied, e.g., glucose and lipid homeostasis are well known
to exhibit circadian variation. Therefore, molecular clock may play important
roles in regulation of metabolic activity in adipocytes. In a previous study, we
reported that white adipose tissue contains functional molecular clock and
expression of several adipocytokines including leptin and plasminogen activator
inhibitor-1 displays circadian rhythm. The diurnal rhythm in the level of these
molecules suggests that molecular clock is, at least partly, associated with the
onset of metabolic syndrome.
PMID- 17037375
TI - [Postoperative adjuvant therapy for premenopausal patients with breast cancer].
AB - The age peak of breast cancer morbidity is younger in Japan in comparison with
that in Western countries. This results in a higher incidence of premenopausal
patients in Japan. There are specific concerns on the postoperative adjuvant
therapy for premenopausal patients, such as its influences on pregnancy, delivery
and lactation, and acute and chronic adverse events related to earlier ovarian
dysfunction. International guidelines such as the recommendations by the St.
Gallen consensus conference provide clinicians with useful information on the
risk assessment for recurrence and treatment selection of postoperative adjuvant
therapy. Recommendations on postoperative adjuvant therapy for premenopausal
breast cancer patients are presented according to the guidelines and evidence
established by clinical trials. On-going clinical trials to resolve unanswered
questions on the adjuvant therapy are also reviewed. Finally, future perspectives
on the adjuvant therapy are discussed.
PMID- 17037377
TI - [Basic evaluation for new antimicrobial susceptibility testing of Mycobacterium
leprae by bioluminescence assay (ATP method)].
AB - Antimicrobial susceptibility testing of Mycobacterium leprae by non-radioactive
bioluminescence assay was developed. Optimization of the assay conditions such as
temperature and time for ATP extraction, bacteria dose, preparation of bacteria
suspension and pH of culture medium was carried out using M. leprae Thai 53
strain. Samples of bacterial suspension of M. leprae were first treated with
filamentous cell treatment reagent at room temperature for 30 minutes and ATP was
extracted from the leprosy bacilli by heating at 60 degrees for five minutes.
Luciferin luciferase was added to the extract after cooling to room temperature
followed by measurement of relative light units (RLU) of each sample using a
luminometer. The concentrations of the drugs used for the evaluation of
antimicrobial activities of rifampin (RFP), clofazimine (CLF), ofloxacin (OFLX)
and clarithromycin (CAM) were 0.125, 0.50, 2.0 and 8.0 microg/ml respectively.
Middlebrook 7H9 broth medium was used (pH6.6) as the basal medium and the bacilli
were cultivated at 32 C for 0-14 days. ATP was extracted from 0.1 ml of culture
suspension and inhibition of the luminescent activity was calculated. The results
were compared to that obtained by radio-active CO2 detection system, Buddemeyer
method which is commonly used for measuring anti-M. leprae activity. There was a
good correlation between the results obtained by ATP method on the tenth day of
culture and the results obtained by Buddemeyer method on the seventh day of
culture. ATP method may be useful for the determination of drug susceptibility
ofM. leprae.
PMID- 17037376
TI - [Guideline for the treatment of Hansen's disease in Japan (Second edition)].
AB - ad hoc committee of Japanese Leprosy Association recommends revised standard
treatment protocol of leprosy in Japan, which is a modification of World Health
Organization's multidrug therapy (WHO/MDT, 1997). For paucibacillary (PB)
leprosy, 6 months treatment by rifampicin and dapsone (MDT/PB) is enough.
However, for high bacterial load multibacillary (MB) leprosy, 12 months treatment
seems insufficient. Thus, (A) For MB with bacterial index (BI) > or = 3 before
treatment, 2 years treatment by rifampicin, dapsone and clofazimine (MDT/MB) is
necessary. When BI become negative and active lesion is lost within 2 years, no
maintenance therapy is necessary. When BI is still positive, one year of MDT/MB
is added (3 years in total), followed by maintenance therapy by dapsone and
clofazimine until BI negativity and loss of active lesions. (B) For MB with BI <
3 or fresh MB (less than 6 months after the onset of the disease) with BI > or =
3, 1 year treatment by MDT/MB is necessary. When BI become negative and active
lesion is lost within one year, no maintenance therapy is necessary. When BI is
still positive or active lesion is remaining, additional therapy with MDT/MB for
one more year is recommended. This is a simplification of first version in 2000.
Brief summary of diagnosis, purpose of therapy, character of drugs, and
prevention of deformity is also described.
PMID- 17037378
TI - [Leprosy services following elimination in WPRO and SEARO regions].
AB - The elimination of leprosy with the advent of multidrug therapy (MDT) is one of
the success stories in public health. Elimination will be achieved in the regions
of Western pacific and South-East Asia in near future. A biregional consultation
between the WHO South-East Asia and Western Pacific regions was held in the end
of 2004 in Manila, the Philippines. A strategy document was developed during the
consultation, to sustain quality leprosy services in Asia and the Pacific beyond
2005, and to further reduce the leprosy burden. The main strategy involves timely
detection of new cases, multidrug treatment, and the key element of integration
of leprosy services into general health services.
PMID- 17037379
TI - [Recent condition of new leprosy patients in Japan].
AB - Most of 148 newly registered leprosy patients in the past 10 years from 1995 to
2004 in Japan had received some examinations, such as histopathology test (85%),
skin smear test (84%), estimation of PGL-I antibody titer (55%) or detection M.
leprae with PCR method (41%). 17% of newly patients should receive wrong therapy,
if they had not had aforesaid clinical examinations in addition to count skin
lesions. Improvement of technical level at skin smear test should be required for
accurate treatment program in Japan. In Japanese patients, the number has been
decreasing year by year; epidemiological condition was different between in
Okinawa prefecture and in others, about ratio of sex, kind of type and age group.
PMID- 17037380
TI - Leprosy situation in Brazil.
AB - We present the situation of leprosy in Brazil, reporting about epidemiology,
clinical criteria for classification, multidrugtherapy and special situations, as
co-infection. This material was presented in the 79th Annual Meeting of Japanese
Hansen's Disease Association in May 2006, during a discussion about the Japanese
Guidelines for leprosy treatment.
PMID- 17037381
TI - [Current practice of genetic diagnosis for Mycobacterium leprae].
AB - Laboratory tests necessary for the diagnosis of leprosy have not been well
introduced in general hospitals and clinical laboratories. Therefore, several
tests have been performed in Leprosy Research Center, National Institute of
Infectious Diseases since July, 1997, as a part of administrative examinations
(tests done by request of Ministry of Health, Labour and Welfare). These
examinations include histopathology, serum antibody titers (anti-PGL-I antibody),
PCR test and bioactivity of anti-bacterial agents.
PMID- 17037382
TI - [Development of rapid and simple genomic diagnostic method].
AB - To develop the rapid and simple genomic diagnostic method, we analyzed the
partial dnaA sequence of 27 mycobacterial species. The partial dnaA sequence
could distinguish M. kansasii and M. gastri. Based on this region and RLEP
sequence of M. leprae, we established the loop-mediated isothermal amplification
method (LAMP) to detect each species. The LAMP method for M. kansasii and M.
gastri, could detect 500 copies. Five copies of M. leprae genomic DNA could be
detect in 30min. To simplify the sample processing, the LAMP assay was performed
with FTA filter paper. M. leprae bacilli were applied on filter paper that lyses
bacilli and bound DNA, eliminating sample centrifugation and extraction
procedures. Assays of number standards showed reproducible detection rate 50
bacilli of M. leprae. Thus, The LAMP assay combined with FTA card has the
advantages of rapid and simple detection and provides a practical, economical,
and specific method for the diagnosis of M. leprae and NTM infection.
PMID- 17037384
TI - [Identification of an immunodominant antigen of Mycobacterium leprae and its
application for the development of protective measures].
AB - Host defense against Mycobacterium leprae (M. leprae) is chiefly conducted by
cellular immunity. The adaptive immunity plays an important role, and T cells are
activated through recognition of some immunodominant antigens of M. leprae. A
search for an immunodominant antigen was carried out using human peripheral
monocytes-derived dendritic cells and M. leprae-derived cell membrane fraction
which is the most antigenic fraction of the bacteria, and Major Membrane Protein
(MMP)-II was found as one of the immunodoninant antigens. The MMP-II highly
stimulated both dendritic cells and macrophages to produce various cytokines.
Further, MMP-II was recognized by T cells in vivo in patients infected with M.
leprae. Then, we constructed a recombinant BCG secreting MMP-II. The recombinant
BCG strongly stimulated both naive CD4+ and naive CD8+ T cells, and seemed to be
a useful immunostimulatory agent.
PMID- 17037383
TI - [DNA microarray based rapid drug susceptibility test for Mycobacterium leprae].
AB - Antibiotic susceptibility test of Mycobacterium leprae still relies on the time
consuming methods based on the growth of M. leprae in the mouse footpad. Thus,
the establishment of a rapid, simple and reliable method for the detection of
drug-resistant M. leprae is one of the most urgent subjects in the treatment of
leprosy patients. Recently, many data on the mutation of specific genes
correlating with drug resistance have been accumulated. Application of these data
permit the establishment of new gene diagnostic methods for drug susceptibility
test of leprosy. In this paper, the method using the low density oligonucleotide
array that enables the detection of base substitutions involved in resistance
against anti-leprosy drugs on a single platform was discussed. The low density
oligonucleotide array described in this paper will open the new perspectives in
terms of patient management for leprosy with low cost requirement.
PMID- 17037385
TI - Diagnosis of leprosy: serological aspects.
AB - The most convenient way of diagnosing an infectious disease is by serological
methods. To improve the quality of diagnosis in leprosy, simple tests in addition
to diagnosis by clinical signs, are necessary. Here, PGL-I based methods for
detection of multibacillary and paucibacillary leprosy, have been revisited and
newer methods are discussed.
PMID- 17037386
TI - [Present situation of falling accidents in leprosy hospitals].
PMID- 17037387
TI - [Identification of mycobacteria by sequencing of rpoB gene and 16S rRNA].
AB - PURPOSE: To classify a specific Mycobacterium among various mycobacteria
utilizing sequencing of rpoB gene. To classify mycobacteria not identified by DNA
DNA hybridization (DDH) using sequencing of rpoB and 16S rRNA gene. OBJECTS AND
METHODS: Classification of 106 Mycobacteria strains, one Nocardia strain, one
Rhodococcus strain, four Gordona strains was made by using partial sequencing of
rpoB and 16S rRNA (RIDOM). Thereafter, 38 mycobacteria clinical strains not
identified by DDH were classified utilizing the DNA sequencing data. RESULTS:
Pairs of M. kansasii and M. gastri, M. abscessus and M. chelonae, M.fortuitum
(ATCC49404) and M. polcinum, M. peregrinum and M. septicum, M. farucinogense and
M. senegalense and M. fortuitum (ATCC49403), Rhodococcus, Nocardia and Gordona
strains were classified using sequencing of rpoB gene. Even though sequencing of
rpoB and 16S rRNA gene was utilized, it was impossible to classify M.
tuberculosis complex, M. avium family, M. marinum and M. ulcerans, and M.
fortitum subsp. fortuitum and M. fortuitum subsp. acetamidolyticus. The 38
mycobacteria clinical strains not identified by DDH were successfully classified
using sequencing of both rpoB and 16S rRNA. These sequencing analyses showed that
M. heckeshornense, M. branderi, M. intermedium, M. shimoidei, M. wolinskyi, M.
malmoense and M. lentiflavum could be identified. Thirty six clinical isolates
(94.7%) and 32 clinical isolates (84.2%) were identified by rpoB sequencing and
16S rRNA sequencing (RIDOM), respectively. CONCLUSION: The classification ratio
of mycobacteria including Nocardia, Rhodococcus and Gordona is 69.6% for
sequencing of 16S rRNA and 89.3% for sequencing of rpoB gene. Sequencing of rpoB
is useful for classification of mycobacteria due to its genetic diversity, but
has some limitation in its application. In order to classify mycobacteria more
accurately, it is important to combine sequencing of rpoB and 16S rRNA and
biochemical/biological tests.
PMID- 17037388
TI - [Usefulness of variable numbers of tandem repeats typing in clinical strains of
Mycobacterium avium].
AB - OBJECTIVES: We evaluated the usefulness of Variable Numbers of Tandem Repeats
(VNTR) analysis, which was recently reported as a new typing method of
Mycobacterium avium strains of animal origin, for strain differentiation of
clinical isolates of M. avium in comparison with the standard IS1245-RFLP typing
method. In addition, forty M. avium isolates recovered from sputum samples of
same patient in different times were analyzed with VNTR typing method. SUBJECTS
AND METHODS: The subjects were twenty-four clinical isolates of M. avium stocked
at Higashi Nagoya National Hospital and discriminatory power was evaluated with
Hunter Gaston Discriminatory Index (HGDI). Furthermore, forty M. avium isolates
recovered from sputum samples of one patient obtained at four different times
were analyzed by using this VNTR typing method. RESULTS: VNTR typing showed
better discriminatory power for twenty-four clinical isolates than IS1245-RFLP
method (HGDI: 0.975 vs 0.866). In the second study, polyclonal infection of four
genotype strains with different allele profiles were detected. The ratio of
mixture of the four different genotype strains varied during clinical course.
CONCLUSION: We considered that VNTR typing method was very useful for
discriminatory examination of M. avium.
PMID- 17037389
TI - [Influence of aging on tuberculosis infection--an epidemiological study of 1,141
smear-positive TB patients].
AB - OBJECTIVES: To elucidate the influences of aging on the tuberculosis infection.
SUBJECTS AND METHODS: The subjects of this retrospective study were 1,141 smear
positive pulmonary tuberculosis (TB) patients registered in Aichi prefecture
between 1989 and 2003. All registration files were reviewed to identify
epidemiological links of patients. When linked patients with an interval of the
dates of registration of less than 10 years were found, the earliest case was
considered as the source case, and the other patients were regarded as secondary
cases. An epidemic source rate (ESR) for a category of patients (e.g., age-group,
etc.) was defined as following; ESR= NS/NA X 100, where NA: Number of smear
positive pulmonary TB patients in a category A, and NS: Number of source cases in
category A. RESULTS: A total of 70 source cases were identifed and the ESR was
6.1%. The ESRs for different age-groups were; 14.3 % for 10-19 years of age (NA =
14), 13.5% for 20-29 years (NA = 74), 14.6% for 30-39 years (NA = 48), 15.0% for
40-49 years (NA = 107), 6.9% for 50-59 years (NA = 145), 3.5% for 60-69 years (NA
= 227), 3.8% for 70-79 years (NA = 293), 2.8% for 80-89 years (NA = 212), and 0%
for 90-99 years (NA = 21). The ESR were significantly different between those
aged 40 to 49 years and those aged 50 to 59 (p<0.05). The ESR was significantly
different between those aged 59 years and younger and those aged 60 years or
older (11.6% vs 3.3%, p<0.001). The ESR was significantly different between those
patients with cavitary lesion and those with noncavitary lesion in the younger
groups (14.3% vs 5.2%, p<0.01), as well as in the elder age-groups (4.8% vs 1.7%,
p<0.01). The rate in the younger groups was 6.3% for those with lower smear
positivity (Gaffky 1 to 4), compared with 15.3% for those with intermediate smear
positivitiy (Gaffky 5 to 8), and 32.4% for those with higher smear-positivity
(Gaffky 9 and 10) (with p<0.01, p<0.05 respectively), while the rates were 3.1%,
3.9%, and 3.4%, respectively in the older groups. CONCLUSION: These findings
suggest that the infectivity is significantly lower in older groups.
PMID- 17037390
TI - [Comparison between direct smear by Ziehl-Neelsen and concentrated smear by
fluorochrome stain].
AB - PURPOSE: For the purpose of supporting more completely our assertion that two
times concentrated sputum smear tests by fluorochrome stain are more sensitive
than or at least equal to 3 times direct smear tests by Ziehl-Neelsen stain, we
compare the sensitivity of concentrated smear by stain (conc-smear) and direct
smear by Ziehl-Neelsen stain (di-smear). OBJECT AND METHOD: Retrospective study
of sputum acid-fast smear tests in our hospital with tuberculosis ward from Jan.
1, 2003 to Sep. 30, 2005. RESULT: 170 of 899 sputums on which both conc-smear and
di-smear were done, were smear positive by at least one of the two smear method.
Of those 170, 167 (98.2%) were positive by conc-smear and 113 (66.5%) were
positive by di-smear, and the difference was statistically significant (p<0.001).
Of those 110 that were positive by both conc-smear and di-smear, in 65 (59.1%)
smear grade by conc-smear were higher than that of di-smear, and in 3 (2.7%)
smear grade by di-smear were higher than that of conc-smear. Smear grades in conc
smear were significantly higher than that of di-smear (p< 0.001). CONCLUSION: In
sensitivity and smear grades, conc-smear was superior to di-smear. Together with
previous report, 2 times conc-smear tests are supposed to be superior to 3 times
di-smear.
PMID- 17037391
TI - [A case of lung tuberculosis showing no chest radiograph findings with recurrent
hemoptysis].
AB - A 59-year-old male was referred to our hospital because of hemoptysis. A chest X
ray film and 7 mm-slice CT scan showed no abnormal finding. Bronchoscopy revealed
hemorrhage in the right upper bronchus (B1a) Bronchial lavage of the lesion was
performed, but Mycobacterium tuberculosis was not detected. Because of repeated
hemoptysis, he was admitted to our hospital. Right bronchial artery angiograph
showed vascular hyperplasia in the peripheral part of the upper lobal branch, and
this lesion was suggested to be a bleeding point. There were no vascular
malformations. Thin slice (0.5 mm-thick) CT scan showed mild infiltrative shadow
in the right upper lobe. After admission, sputa smear for mycobacteria and PCR
for M. tuberculosis became positive, and he was diagnosed as pulmonary
tuberculosis. After starting antituberculous chemotherapy, hemoptysis
disappeared, and sputa smear and culture for mycobacteria converted to negative.
This case suggests that lung tuberculosis should be suspected in patients having
hemoptysis, even though they had no chest X-ray film abnormality.
PMID- 17037392
TI - [Chlamydia pneumoniae infections].
AB - Chlamydia pneumoniae, an obligate intracellular human pathogen, causes infections
of the respiratory tract. It is a significant cause of both lower and upper acute
respiratory illnesses, including pneumonia, bronchitis, pharyngitis and
sinusitis. Most respiratory infections caused by C. pneumoniae are mild or
asymptomatic. Some studies have suggested a possible association of C. pneumoniae
infection and acute exacerbations of asthma and chronic obstructive pulmonary
disease (COPD). Seroepidemiological studies showing antibody prevalence rates in
a range of 50 to 70% suggest that C. pneumoniae is widely distributed and that
nearly everybody is infected with the agent at some time. C. pneumoniae can cause
prolonged or chronic infections which may be due to persistence for months or
years. These persistent infections have been implicated in the development of a
number of chronic diseases including atherosclerosis, asthma and COPD. These
persistent chlamydial infections can be established in vitro using several
methods including cytokines, antibiotics and deprivation of certain nutrients.
Despite differences in treatment, chlamydiae respond to form inclusions
containing atypical reticulate bodies (RBs), which occasionally have been shown
to be pleomorphic forms, termed aberrant form (AF). The AF is generally larger in
diameter than typical RBs, and display a sparse densinometric appearance. In
general, it is likely that this aberrant developmental step leads to the
persistence of viable but nonculturable chlamydiae within infected cells over
long periods. Removal of several stress factors described above results in the
condensation of nuclei, the appearance of late proteins, and the production of
viable, infectious elementary bodies (EBs). Most of the major sequelae of
chlamydial disease are thought to arise from either repeated or persistent
chlamydial infection of an individual. The persistence would allow constant
presentation to the individual immune response of these potentially deleterious
immune targets. Since repeated infection can certainly be documented in many
clinical settings, persistence is thought to also play a role.
PMID- 17037393
TI - Establishment of a clinical pathway as an effective tool to reduce
hospitalization and charges after video-assisted thoracoscopic pulmonary
resection.
AB - OBJECTIVE: The purpose of this study was to assess the effect of establishing a
clinical pathway based on the length of hospitalization, hospital charges, and
the outcome for video-assisted thoracoscopic pulmonary resection (VATPR).
METHODS: We retrospectively analyzed consecutive patients who were diagnosed as
having primary lung cancer, metastatic lung cancer, or a nodule that was
suspected to be malignant and thus was operated on using VATPR during the 1-year
period before (n = 105) and after (n = 113) pathway implementation. RESULTS: The
mean economic cost and total hospital stay before and after pathway
implementation were about dollars 14439 and dollars 13093 (US), and 29.4 and 18.6
days, respectively. These figures were significantly lower after pathway
implementation than before establishment of the pathway. CONCLUSION: A clinical
pathway is thus considered useful for reducing the length of total hospital stay
and the costs associated with VATPR while maintaining high-quality postoperative
care.
PMID- 17037394
TI - Comparison of surgical outcome using the prediction scoring system of E-PASS for
thoracic surgery.
AB - OBJECTIVE: The purpose of this study was to determine if our predictive scoring
system, E-PASS, can estimate the surgical outcome. METHODS: We conducted a
multicenter cohort study for 3 years in four national hospitals. A consecutive
series of 731 patients who underwent elective thoracic operations were analyzed.
The preoperative risk score (PRS) and the comprehensive risk score (CRS) of the E
PASS were determined preoperatively and immediately after the operation,
respectively. The cost of the surgical admission and the severity of the
postoperative complications were recorded at the time of discharge. RESULTS: The
CRS significantly correlated with the severity of the postoperative complications
(rs = 0.728, P < 0.0001) and the charge (rs = 0.530, P< 0.0001). When the
estimated/real morbidity ratio (MR) among the hospitals was compared, it varied
from 0.16 to 0.59. A significant increase in the cost was observed according to
the CRS. CONCLUSION: The E-PASS scoring system may be useful for standardizing
the patient population and surgical severity to compare the surgical outcome.
PMID- 17037395
TI - Primary malignant melanoma: a rare cause of mediastinal mass.
AB - A case of primary malignant melanoma in the mediastinum presenting as recurrent
laryngeal nerve palsy is reported. Tissue biopsy at mediastinotomy yielded a
diagnosis of malignant melanoma. The mass was fixed to the left aspect of the
trachea and to the upper border of the left main bronchus and could not be
removed surgically. Further extensive clinical and radiological investigations
revealed no evidence of tumor elsewhere in the body.
PMID- 17037396
TI - Nodular pulmonary amyloidosis.
AB - A 72-year-old woman with a diagnosis of suspected rheumatoid arthritis was
admitted with multiple pulmonary nodules in the bilateral lung field. To obtain a
diagnosis, a nodule was resected using video-assisted thoracic surgery.
Microscopically, amorphous eosinophilic acellular substances were surrounded by
inflammatory infiltrates, which were confirmed to be amyloid deposits by congo
red staining. Thus, a diagnosis of pulmonary amyloidosis was obtained. The
clinical features and diagnostic process are discussed.
PMID- 17037397
TI - Chest wall defect and chronic pleural infection: surgical treatment with
thoracomyoplasty and open window thoracostomy.
AB - We report a rare case of a 75-year-old hemiplegic man with a chronic pleural
infection, a bronchopleural fistula, and a full-thickness defect of the chest. In
one operation we performed open-window thoracostomy and pleural decortication as
well as reconstruction of the chest defect and reclosure of the bronchopleural
fistula with a latissimus dorsi muscle flap. The patient made a good recovery and
was sent for rehabilitation in good condition. Surgical treatment was essential
to control and ultimately halt the septic process. Use of a muscle transplant in
a hemiplegic patient did not reduce mobility.
PMID- 17037398
TI - Giant cell tumor of the sternum.
AB - A primary giant cell tumor (GCT) originating from the sternum is extremely rare.
We report a case of a GCT originating from the sternum in a 45-year-old man who
was referred to us for a mass in the anterior chest wall that had been growing
slowly. Computed tomography revealed a soft tissue mass involving a large
osteolytic and destructive lesion of the sternum body. Subtotal sternectomy and
reconstruction with methylmethacrylate were performed. The tumor was 8.5 x 4.5 x
2.5cm, and the histopathological examination confirmed GCT. Radical wide
resection of primary sternum tumors and reconstruction with an appropriately
rigid prosthetic material are necessary to minimize local recurrence.
PMID- 17037399
TI - Compromised video-assisted thoracoscopic segmental resection for high-risk
patients with stage I lung cancer near the lung hilum.
AB - We performed a video-assisted thoracoscopic segmental resection without doing a
mini-thoracotomy in two patients (one octogenarian and one with poor lung
function) with early stage (T1-2N0) lung cancer located at the lung hilum who
required preservation of their cardiopulmonary function. After 2 years of follow
up, both patients are alive without recurrence. We describe the cases and the
method used for the video-assisted thoracoscopic segmental resection using an
endoscopic stapler.
PMID- 17037400
TI - Simultaneously performed mitral valve replacement and Hartmann's operation for
infectious endocarditis from Streptococcus bovis and rectal cancer.
AB - In patients with surgical indications for both cardiac surgery and a malignant
neoplasm, cardiac surgery should generally be performed first; however, in some
cases simultaneous surgery is recommended. We report a case of infectious
endocarditis of the mitral valve caused by Streptococcus bovis with rectal
cancer. Blood cultures showed a rise in coagulase-negative S. bovis, and the
source of infection was thought to be the rectal cancer. The patient presented
with cerebral infarction prior to surgery, and the possibility of recurrence of
an infarction was predicted. The tumor of the rectum was hemorrhagic, so to avoid
hemorrhagic complications due to perioperative heparinization and anticoagulant
therapy and to remove the source of infection, mitral valve replacement and a
Hartmann's operation were performed simultaneously. The postoperative course was
uneventful.
PMID- 17037401
TI - Primary pulmonary sarcomatoid carcinoma with intracardiac extension.
AB - Primary pulmonary sarcomatoid carcinoma is rare. It is generally regarded as an
aggressive tumor. We report, to our best knowledge, the first case of pulmonary
sarcomatoid carcinoma with extensive intracardiac spread. This case illustrated
the misleading clinical features of this condition. Previous literature is also
reviewed.
PMID- 17037402
TI - Clopidogrel (PLAVIX) increases risk of bleeding in a patient undergoing coronary
artery bypass grafting.
PMID- 17037403
TI - [Clinical study of 90 cases of Mycoplasma pneumoniae pneumonia].
AB - We investigated 90 patients with Mycoplasma pneumoniae (M. pneumoniae) pneumonia.
Forty-four patients were men, 46 were women and the mean age was 43.1 years old.
Twenty-nine patients were smokers and 28 had underlying diseases. As for
diagnostic method, 16 were culture positive, 71 had a fourfold increase in
antibody titer to M. pneumoniae, and 3 were both culture positive and had a
fourfold increase in antibody titer. Regarding the degree of severity, 21
patients were classified as severe according to Japanese Respiratory Society
diagnostic criteria, 11 patients were diagnosed as severe according to American
Thoracic Society diagnostic criteria. Partial pressure of arterial oxygen (PaO2)
of 18 patients were <60mmHg, 5 patients were under mechanical ventilation, and 3
patients died. Three of 16 patients treated with only beta-lactum antibiotics
recovered. The 3 patients who died were M. pneumoniae culture-positive and two
patients had polymicrobial infections. Severe pneumonia associated with
Mycoplasma pneumoniae infection is not unusual. If a rapid diagnosis kit or
culture method of M. pneumoniae pneumonia is not introduced, the pathogen might
be unknown in cases of rapid death due to M. pneumoniae pneumonia. These data
suggest that the mortality rate of M. pneumoniae pneumonia might be
underestimated without these detection tests.
PMID- 17037404
TI - [Clinical features of Pneumocystis pneumonia in patients with systemic lupus
erythematosus].
AB - Systemic lupus erythematosus (SLE) is often associated with various opportunistic
infections, particularly during treatment with corticosteroids or
immunosuppressants. We studied the clinical characteristics of 15 patients with
SLE who underwent diagnostic bronchoalveolar lavage (BAL) and compared 6 patients
with confirmed Pneumocystis pneumonia (PcP+), with 9 patients without
Pneumocystis pneumonia (PcP-). The serum concentrations of beta-D-glucan and KL-6
were significantly higher in PcP+ than in PcP- patients, whereas serum LDH was
similar in both groups. The serum concentrations of complement, a marker of SLE
activity, and of IgG did not predict the presence of PcP. In all patients, the
overall cell and lymphocyte counts were increased in the BAL fluid, without any
significant difference between the PcP+ and PcP- groups. Ground-glass opacities
on chest computed tomography, and oxygenation impairment (PaO2/FiO2<200Torr) were
more common in PcP+ than PcP- patients. We concluded that, in patients with SLE,
serum beta-D-glucan and KL-6 might be useful in the diagnosis of PcP,
particularly when severe hypoxemia precludes BAL.
PMID- 17037405
TI - [Gastropleural fistula due to perforated gastric ulcer].
AB - A 65-year-old woman, who had been taking non-steroidal anti-inflammatory drugs
(NSAIDs), prednisolone and methotrexate for rheumatiod arthritis, was admitted to
our hospital with a sudden onset of left-back and chest pain and breathlessness.
A chest radiograph and computed tomography revealed a left-side pneumothorax and
pleural effusion. Chest tube was inserted for drainage and the fluid was formed
to contain food residuum. Contrast radiography demonstrated escape of soluble
contrast medium into the left pleural space. A thoracotomy and transdiaphragmatic
revealed a gastropleural fistula. It was repaired and the gastric origin was
resected. Pathologic evaluation revealed evidence of chronic peptic ulceration,
but no malignant change. Gastropleural fistula due to peptic ulcer without
esophageal herniation, malignancy, or traumatic injury is extremely unusual. The
cause of the focal adhesion of the gastric ulcer and diaphragm, fistula formation
was not certain but was probably related to the ingestion of NSAIDs in
combination with prednisolone and other immunosuppressive agents. Although
gastropleural fistula is rare, the prognosis in such patients related to early
diagnosis and surgical intervention, emphasizing the importance of including this
condition when making a differential diagnosis.
PMID- 17037406
TI - [Identification of propionibacterium acnes in a case with stage III pulmonary
sarcoidosis involving hepatosplenic disease].
AB - A 35-year-old woman was admitted to our hospital because of an abnormal chest
radiograph. Chest X-ray on admission showed multiple small nodular shadows in
both lung fields but no bilateral hilar lymphadenopathy (BHL). Moreover,
abdominal CT showed some nodules in the liver and spleen, and serum ACE was
slightly increased to 23.3U/L (normal range: 8.3-21.4U/L). Transbronchial lung
biopsy and liver biopsy resulted in a diagnosis of stage III pulmonary
sarcoidosis with hepatosplenic disease. Histopathological findings demonstrated
non-caseating epithelioid cell granulomas with giant cells in both specimens.
Interestingly, propionibacterium acnes (P. acnes), the possible pathogen of
sarcoidosis, was detected in giant cells in the lung and epitheliod cell
granuloma of liver tissue. This case was of interest considering P. acnes might
have been the causative pathogen.
PMID- 17037408
TI - [A case of Heerfordt's syndrome with an elevated serum TNF alpha].
AB - A 27-year old man who had developed uveitis, swelling of the right parotid gland,
right facial nerve paralysis and fever, was admitted to our hospital. A chest X
ray film showed bilateral hilar lymphadenopathy. Serum levels of angiotensin
converting enzyme and lysozyme were elevated. Histological findings of
transbronchial lung biopsy specimens showed non-caseous epithelioid cell
granulomas. Therefore, sarcoidosis was diagnosed. This case also fulfilled the
criteria for Heerfordt's syndrome. Adiministration of prednisolone (PSL)
initially improved the patient's symptoms, but rapid tapering of PSL worsened his
symptoms. Thus, administration of high-dose PSL for a long time was required. He
also showed elevated levels of TNF alpha in serum.
PMID- 17037407
TI - [A case of pulmonary adenocarcinoma accompanied by minimal change nephrotic
syndrome, antiphospholipid syndrome and warm-type autoimmune hemolytic anemia].
AB - A 49-year-old man was urgently admitted due to edema in both leg and left toe
pain. A chest radiograph revealed a solitary nodule in the right lung field.
Detailed investigations including bronchoscopy and renal biopsy led to a
simultaneous diagnosis of clinical stage IIIB pulmonary adenocarcinoma, minimal
change nephrotic syndrome, antiphospholipid syndrome, and warm-type autoimmune
hemolytic anemia. Prednisolone was administered for nephrotic syndrome,
antiphospholipid syndrome and warm-type autoimmune hemolytic anemia, and 6
courses of chemotherapy with 70Gy radio-therapy were performed. The pulmonary
nodule significantly decreased in size and the other three autoimmune diseases
appeared to be well-controlled. Thirteen months after admission, multiple brain
metastases developed along with worsening antiphospholipid syndrome symptoms
including lupus anticoagulant. Following whole-brain irradiation, the brain
metastases decreased in size and antiphospholipid syndrome symptoms improved.
Thirty-nine months after the initial visit, the primary lung cancer, its brain
metastasis and the 3 other autoimmune diseases appeared to be well-controlled.
The temporal correlation of the lung cancer and the three autoimmune diseases
suggests the latter may be paraneoplastic syndrome.
PMID- 17037409
TI - [A case of successful bronchial artery embolization for primary racemose
hemangioma with massive hemoptysis].
AB - We encountered a case of primary racemose hemangioma treatment with successful
bronchial artery embolism for massive hemoptysis. A 56-year-old woman with
massive hemoptysis was transported to our hospital. The source of the massive
hemoptysis was observed to be from around a non-pulsatile polyp covered by normal
mucosa occluding the truncus intermedius by fiberoptic bronchoscopy. We stopped
the bleeding temporarily using differential lung ventilation, and then bronchial
artery angiography was performed. The main right bronchial artery was enlarged,
and enlarged and convoluted right peripheral bronchial vessels were also
observed. We diagnosed the massive bleeding to be due to racemose hemangioma. A
successful bronchial artery embolization (BAE) was performed with gelforms and
metallic coils for the treatment of racemose hemangioma. There has been no
recurrence of hemoptysis for one year after BAE. There have been many reports on
massive hemoptysis as in this patient who were treated by lobectomy, nevertheless
we would like to state BAE should be considered as a suitable treatments for
primary racemose hemangioma with hemoptysis if there is no recognizable shunt
artery.
PMID- 17037410
TI - [A couple suffering acute respiratory illness due to waterproofing spray
exposure].
AB - The patients were a 28-year-old man and a his 27-year-old wife. The husband
smoked a cigarette immediately after using a waterproofing spray, and developed
fever, cough, and dyspnea 15 min later. The wife had nausea 2 hours later. Nine
hours later, the husband visited a local clinic, and was referred to our hospital
because of hypoxemia. In addition, chest CT showed ill-defined areas of increased
density, predominantly in the bilateral upper lung fields, with interlobular
septal thickening, and he was hospitalized. Although the wife was asymptomatic at
the time of examination, she had chest CT findings similar to those of her
husband, and was also hospitalized. After admission, the husband received steroid
pulse therapy and oxygen inhalation for his symptoms and hypoxemia, with return
of arterial blood gas analysis results to normal on the third day. The wife had
no symptoms or hypoxemia during her hospital stay. Their chest CT findings
improved on the seventh day after admission, and they were discharged. Thus, it
appears that the couple suffered from acute respiratory illness due to
waterproofing spray exposure, and probably heat degradation products from
cigarette smoking caused the husband to have severe symptoms.
PMID- 17037411
TI - [Two lung adenocarcinoma patients with multiple brain metastasis treated with
Gefitinib and surviving more than 2 years].
AB - Case 1 is a 78-year-old woman in whom lung adenocarcinoma with multiple brain
metastasis (cT2N3M1, stage IV) was diagnosed. She was treated with Gefitinib
alone. Her lung tumor and metastatic brain lesions decreased 6 months after the
start of therapy. She has no recurrence and is still alive with a good
performance status after 25 months. Case 2 is an 80-year-old woman in whom lung
adenocarcinoma with multiple brain (cT2N3M1, stage IV) was diagnosed. She was
also treated with Gefitinib alone and her lung tumor and metastatic brain becomes
improved 6 months after the start of therapy. She maintained a good performance
status for more than 2 years (29 months). However, 29 months after beginning
treatment, she had recurrence in bone and died 2 months later, 31 months after
the start of therapy. The prognosis of non-small cell lung cancer with multiple
brain metastasis is very poor and the efficacy of chemotherapy for the treatment
of multiple brain metastases is limited, and longterm survival remains
disappointing. We report two lung adenocarcinoma patients with multiple brain
metastasis who survived more than 2 years by treatment with Gefitinib alone.
PMID- 17037412
TI - [An autopsy case of Aspergillus pneumonia after inhalation of a great deal of
dust in a mushroom factory].
AB - A man in his forties with alcoholic liver injury was referred to our hospital
because of progressive dyspnea and diffuse infiltrative shadows in both lung
fields. Two weeks before admission he had carried a lot of rotten Enoki mushrooms
in his factory, and then inhaled a great deal of airborne dust. Serological
examination showed extremely elevated beta-D-glucan and positive Aspergillus
antigen. Culture of dust collected from the floor of the factory proved to be
positive for Aspergillus fumigatus. Aspergillus pneumonia was diagnosed and
treatment with anti-fungal drugs was started. In spite of intensive treatment he
died of respiratory failure. The autopsy disclosed multiple abscess formation
containing hyphae of Aspergillus fumigatus and granulomatous reaction with
multinuclear giant cells. However, there was no Aspergillus invasion in other
organs. This was a rare case of invasive pulmonary aspergillosis that developed
after inhalation of organic dust in a non-immunocompromised host.
PMID- 17037413
TI - [A case of acute exacerbation of chronic pulmonary thromboembolism with essential
thrombocythemia during treatment for hemoptysis].
AB - An 89-year-old woman with essential thrombocythemia and chronic respiratory
failure was admitted for treatment of hemoptysis. She stopped taking aspirin and
was given tranexamic acid. Though her hemoptysis improved, respiratory failure
suddenly worsened. As a result of various examinations and laboratory findings,
acute exacerbation of chronic pulmonary thromboembolism was diagnosed. Though
there was the risk of recurrence of hemoptysis, she started taking aspirin again.
Her respiratory failure improved but hemoptysis did not reappear. Thrombosis and
hemorrhage are common complications of essential thrombocythemia, however,
pulmonary thromboembolism is a rare complication. There is a possibility that the
exacerbation of this case was caused by tranexamic acid as well as rest and
cessation of aspirin. If a patient with essential thrombocythemia bleeds, we
should be careful when using tranexamic acid.
PMID- 17037415
TI - Time-based E&M coding.
PMID- 17037414
TI - [A case of psittacosis showing a localized peripheral air-space consolidation].
AB - A 29-year-old man was admitted with fever and anorexia. Radiographic examinations
of the chest showed a localized peripheral non-segmental air-space consolidation
in the right lower lobe. He had a history of exposure to parakeets, and
psittacosis was diagnosed based on the elevated serum complement fixation titer
against Chlamydia psittaci. The common radiographic finding of psittacosis is
ground-glass attenuation radiating from the hilar areas. We report a rare case of
psittacosis presenting a localized consolidation, clearly limited to the
subpleural region of the lung.
PMID- 17037416
TI - Getting rid of a computer? Be careful!
PMID- 17037417
TI - Online "visits": insurers pay but docs don't play.
PMID- 17037418
TI - ICD-9: what's new.
PMID- 17037420
TI - In death as well as life.
PMID- 17037419
TI - My cure for Sunday syndrome.
PMID- 17037421
TI - The best EHRs for small practices.
PMID- 17037422
TI - An offer he couldn't refuse.
PMID- 17037423
TI - The doctor is out....
PMID- 17037424
TI - Going not-for-profit saved this doctor's practice.
PMID- 17037425
TI - "Lost chance of survival": the new malpractice risk.
PMID- 17037426
TI - Limit liability for hospital procedures.
PMID- 17037427
TI - ["Doing everything for planning the 2007 elections"].
PMID- 17037428
TI - [Summer universities for an ambitious future].
PMID- 17037429
TI - [Tattoos with henna: attention; danger!].
PMID- 17037430
TI - [Heimlich maneuver].
PMID- 17037432
TI - [Cardiopulmonary arrest].
PMID- 17037431
TI - [Manual respiration using a mask].
PMID- 17037433
TI - [Mouth-to-mouth resuscitation].
PMID- 17037434
TI - [Gastric lavage].
PMID- 17037435
TI - [Emergency vehicles].
PMID- 17037436
TI - [Age-related macular degeneration].
PMID- 17037437
TI - [Professional integration of nursing staff in oncology].
PMID- 17037438
TI - [Swan-Ganz catheters].
PMID- 17037439
TI - [The prerequisite of calculating the dosage].
PMID- 17037440
TI - [Care of patients and preventing back diseases].
PMID- 17037441
TI - [Information on anesthesiology in the operating room].
PMID- 17037442
TI - [Adrenaline].
PMID- 17037443
TI - [Interventional radiology].
PMID- 17037444
TI - [Helping victims of a cerebrovascular accidents].
PMID- 17037445
TI - The relationship of personality and behavioral development from adolescence to
young adulthood and subsequent parenting behavior.
AB - The purpose of the study was to examine the association of parental personality,
behavior, and substance use during adolescence and adulthood as related to the
later parent-offspring relationship. The sample consisted of 297 parents (M age
32 yr.), who were first interviewed at earlier points in their lives in childhood
and early adolescence at six points in time, extending from 1983 to 2002.
Multiple regression models showed that parents with certain earlier personality
and behavioral attributes, e.g., more rebelliousness and more frequent tobacco
use, had a more difficult relationship with their children. Findings indicated an
association between the cumulative number of psychosocial risk factors in the
parents and difficulties in the parent-child relationship. The findings suggested
that interventions designed to decrease youths' substance abuse may increase the
likelihood that later when they are parents they will form nurturing
relationships with their children.
PMID- 17037446
TI - Attitude towards euthanasia in relation to death anxiety among a sample of 343
nurses in India.
AB - Scores on Attitude towards Euthanasia were correlated with scores on Death
Anxiety among 343 female nurses in India using Templer's Death Anxiety Scale and
the authors' 24-item attitude scale. No significant correlation was found between
the two sets of scores (r = -.09) or a nonlinear score on relation. Age of nurses
was not significantly related to Attitude towards Euthanasia (r = .07) or Death
Anxiety (r = .11). As measured, death anxiety has no bearing on attitude about
euthanasia.
PMID- 17037447
TI - A Japanese short form of the Swanson Cognitive Processing Test to measure working
memory: reliability, validity, and differences in scores between primary school
children of the United States and Japan.
AB - The purpose of this study was to examine the reliability and validity of a
Japanese short form of the Swanson Cognitive Processing Test, which assesses
capacity of working memory. Test-retest reliability was acceptable (r = .76).
Concurrent validity was suggested through comparison of scores on the Reading
Span Task (r = .55). Means on the Japanese short form were comparable with means
for the 3 subtests for the older group and 2 subtests for the younger group. With
the exception of the Auditory Digit Sequence, results suggested that both the
Japanese short form and the initial Swanson Cognitive Processing Test measured
comparably the working memory in the two samples of children.
PMID- 17037448
TI - Turnover intentions of the faculty at a teaching-focused university.
AB - Research on turnover in academia suggests faculty primarily resign to obtain
higher salaries and for personal reasons; however, the samples of most such
studies have been from research institutions. Correlates were examined for
turnover intentions among 190 faculty members at a university that emphasized
teaching. Although current turnover intention was low, seven measures of
satisfaction explained 31.5% of the variability in turnover intent, and
satisfaction with pay, work itself, and teaching/service load together explained
26% of the variance. Findings support the hypothesis that salary is an important
element in explaining turnover consideration at teaching institutions. Although
satisfaction with collegial relations was related significantly to turnover
intent, it was not as important as some of the other characteristics.
PMID- 17037449
TI - A simplified version of the SYMLOG Trait Rating Form.
AB - This paper describes a brief measure of Bales's three SYMLOG dimensions. A sample
of 204 undergraduates with a mean age of 24.7 yr., 72.4% of whom were women,
completed the usual version of the SYMLOG Trait Rating Form. This could also be
scored as if it were a simplified version, omitting some items. The Simplified
Measure of the SYMLOG Trait Rating Form correlated fairly highly with the full
form--with r between .87 and .89 for the corresponding versions of all three
scale dimension scores--making it a suitable substitute for research or
illustrative purposes on occasions when respondents' time is of the essence.
PMID- 17037450
TI - Effects of audience awareness on procedural text writing.
AB - Effects of audience awareness were examined. Some participants acted as writers
and the others acted as readers. Writers wrote a text describing a geometrical
figure. Readers read the text and tried to draw the figure according to the
description. In Exp. 1, audience awareness was manipulated among undergraduate
students, 11 men and 34 women. Writers in the high audience-awareness condition
spent more time planning and writing texts than writers in the low audience
awareness condition. Texts in the high audience-awareness condition consisted of
more letters and sentences with descriptions elaborating the texts. In Exp. 2,
prototype texts were constructed based on the results of Exp. 1. Undergraduate
students, 11 men and 47 women, who read the prototype text in the high audience
awareness condition could draw the figure more accurately. In Exp. 3, effects of
feedback from readers were examined. Ninth-grade students, 22 boys and 34 girls,
participated as writers and 7th-grade students, 22 boys and 34 girls,
participated as readers. Merely being told to attend to an audience did not
improve the quality of texts written by 9th-grade students. However, feedback
from the readers who were 7th-grade students was effective. Writers could revise
the texts appropriately according to feedback and improve the quality of texts.
In addition, the experience of revising the text according to feedback
transferred to later writing. Educational implications of the results are
discussed.
PMID- 17037451
TI - Reliability and validity of the Parenting Scale of Inconsistency.
AB - The purposes of the present study were to develop a Parenting Scale of
Inconsistency and to evaluate its initial reliability and validity. The 12 items
assess the inconsistency among parents' moods, behaviors, and attitudes toward
children. In the primary study, 517 participants completed three measures: the
new Parenting Scale of Inconsistency, the Parental Bonding Instrument, and the
Depression Scale of the General Health Questionnaire. The Parenting Scale of
Inconsistency had good test-retest reliability of .85 and internal consistency of
.88 (Cronbach coefficient alpha). Construct validity was good as Inconsistency
scores were significantly correlated with the Care and Overprotection scores of
the Parental Bonding Instrument and with the Depression scores. Moreover,
Inconsistency scores' relation with a dimension of parenting style distinct from
Care and Overprotection suggested that the Parenting Scale of Inconsistency had
factorial validity. This scale seems a potential measure for examining the
relationships between inconsistent parenting and the mental health of children.
PMID- 17037452
TI - A coding scheme for the evaluation of the relationship in music therapy sessions.
AB - This study presents a coding system for observation and monitoring of changes in
the interactive behaviour between patient and therapist during music therapy
sessions. The coding scheme was developed from a psychodynamic framework and
mainly consists of four behavioural classes: Verbal Communication, Nonverbal
Communication, Countenance, and Sonorous Musical Communication. The 15 minutes in
the middle of each videotape concerning the first active music therapy session-
based on the sonorous musical improvisation--were coded. Subjects were children
(4 boys; 3 girls) ages 3 to 10 years (M age = 6.3), diagnosed with Pervasive
Developmental Disorder, and seven therapists. The method for data collection was
continuous recording, applied through The Observer Video-Pro 5.0. For the
reliability indexes there was a substantial agreement between assessments by
video raters.
PMID- 17037453
TI - The plural self and a Taoist orientation in two cultures.
AB - A positive association between having a Taoist orientation to life and unity in
the subjective perception of the self was found in samples of both American (n =
99) and Turkish (n = 100) respondents.
PMID- 17037454
TI - Anxiety and depression in Greek nursing and medical personnel.
AB - The relatively low number of nurses compared to physicians in Greece and the few
available studies on the psychological problems of the health professionals led
to comparison of anxiety and depression for 76 Greek nursing personnel (20 men, M
age: 32.8 yr., SD: 3.8 yr., and 56 women, M age: 36.6 yr., SD: 7.7 yr.) and 66
doctors (35 men, M age: 35.9 yr., SD: 8.9 yr. and 31 women, M age: 32.7 yr., SD:
8.1 yr.) using validated translations of the Spielberger State-Trait Anxiety
Inventory and the Beck Depression Inventory. Male nurses had the lowest scores on
trait anxiety, while female doctors had the highest scores, followed by female
nurses. Depression scores were not different between doctors and nurses,
regardless of sex. Age and depression scores were positively correlated (Spearman
rho = .31) only for the female nurses. The findings suggest that interventions
for diagnosis and stress management in the health-care workplace should be
equally targeted for nursing and medical personnel.
PMID- 17037455
TI - Association of maternal smoking during pregnancy and infant neurobehavioral
status.
AB - The association of maternal smoking during pregnancy with neurobehavioral status
was examined in 344 Japanese infants. Based on a questionnaire, their mothers
were classified into three groups, Nonsmokers, Exsmokers, and Smokers. The
Neonatal Behavioral Assessment Scale was administered three days after birth.
Among the three groups, on the seven clusters and their 28 behavioral subscales
there were no significant differences. The infants of Smokers had lower scores
than those of Exsmokers and Nonsmokers on two behavioral items, general tone and
peak of excitement. General tone remained significant after adjustment for
covariates.
PMID- 17037456
TI - College students' perceived risk and anxiety after reading airplane crash news.
AB - 328 college students in midwest and west coast regions read one of five news
stories (four airplane crash and one irrelevant) or none. They estimated the
likelihood of their victimization in an airplane crash and indicated the maximum
amount of time that they would be willing to spend driving in lieu of flying.
Analysis showed those who read one of the airplane crash stories reported higher
perceived risk of victimization than did those who read the irrelevant story or
none. Reading airplane crash news was not related to the number of hours reported
for driving instead of flying.
PMID- 17037457
TI - Time perspective as a potential tool for psychotherapeutic intervention.
AB - This pilot study shows (1) similarities among adults in the patterns of
organization of the past, present, and future based upon individual imagery and
spatial representation of their personal perspective of their lives and (2) a
relationship between perceived health and future-orientation, i.e., how far into
their future a person imagines self still to be alive. The data support the
concept of a personal spatial representation of past, present, and future (a
timeline) and sets the foundation for the development of psychological
interventions based on this representation for 50 participants (23 men and 27
women). When asked to visualize their personal timelines, subjects indicated a
general pattern of their future spatially located to the right and in front of
themselves; their past was generally located to the left or behind. The distance
into the future seen by participants initially (M +/- SE) were 8 +/- 2.3 yr., 16
+/- 2.8 yr., and 27 +/- 5.5 yr. for the self-reported health status of "poor",
"good", and "excellent", respectively (p < .05). Research must firmly establish
general patterns of spatial representations of time (timeliness) across cultures,
age, race, and beliefs, and explore implications for treatment.
PMID- 17037458
TI - A validity generalization procedure to test relations between intrinsic and
extrinsic motivation and influence tactics.
AB - The relations of intrinsic and extrinsic motivation with use of consultative,
legitimating, and pressure influence tactics were examined using validity
generalization procedures. 5 to 7 field studies with cumulative samples exceeding
800 were used to test each relationship. Significance was found for relation
between agents' intrinsic motivation and their use of consultative influence
tactics and agents' extrinsic motivation and their use of legitimating influence
tactics.
PMID- 17037459
TI - Concordance of self-reported abstinence and measurement of expired air carbon
monoxide in a self-help smoking cessation treatment.
AB - Some self-help programmes for smoking cessation obtain abstinence data entirely
from participants' self-reports. This may lead to overestimation of efficacy. In
the present study, the relationship between self-reported abstinence and expired
air carbon monoxide was evaluated at the 12-mo. follow-up in 200 smokers who had
participated in a self-help programme for smoking cessation conducted by mail.
Analysis indicated a close relationship between carbon monoxide levels and self
reports of smoking status; concordance was about 90%. Studies of the efficacy of
self-help programmes for smoking cessation should include some sort of objective
verification of self-reported abstinence.
PMID- 17037460
TI - Ultimate, provisional, and personal meaning of life: differences and common
ground.
AB - Building on Viktor Frankl's clinical approach of Logotherapy and the works of
subsequent theoreticians, three types of meaning of life were theoretically
derived and empirically investigated, Ultimate, Provisional, and Personal
meaning. These types were characterized, first, by the amount of agreement of
subjects, second, by sources of Life Meaning, which were assessed by content
analyses, third, by correlations, and fourth by prediction with ratings of
important life concepts from the domains of Well-being, Religiosity, and
Prosocial Behavior. 192 German adults, 45 men and 147 women, whose M age was 31.6
yr. (SD = 11.9), participated. Analysis indicated different sources for the
Ultimate meaning compared with the other meaning types, which seem to display
more similarities with each other. Other important life concepts, such as Belief,
Harmony, Happiness, and Human Goodness were related to the investigated types of
meaning of life. Some implications for clinical applications, research
perspectives, and Positive Psychology are discussed.
PMID- 17037461
TI - Further examination of measurement properties of Spanish version of the Sexual
Desire Inventory with undergraduates and adolescent students.
AB - The factor structure and construct validity of a Spanish version of Spector,
Carey, and Steinberg's Sexual Desire Inventory was examined with structural
equation modelling and a nonclinical sample (N = 608). Confirmatory factor
analysis indicated that Dyadic and Solitary sexual desire scales measured two
factorially distinct constructs. Their internal consistency reliabilities were
.87 and .88, respectively. Structural equation analysis indicated that both
subscales are distinguishable from similarly conceptualized correlates of sexual
desire: the Impersonal subscale of the Sex Fantasy Questionnaire and the
Erotophilia measure of the Sexual Opinion Survey. However, the data raised some
questions about an empirical distinction between dyadic sexual desire and
intimate sexual fantasy.
PMID- 17037462
TI - Teachers' conceptions of assessment: validation of an abridged version.
AB - Psychometric characteristics of the abridged Teachers' Conceptions of Assessment
III are reported. Data are from a study of 525 New Zealand primary school
teachers and from a second study of 692 Queensland primary school teachers. The
abridged version of 27 statements using a positively packed response scale had
good fit characteristics for primary teachers in both New Zealand (chi(311)2 =
841.02; RMSEA = .057; TLI = .87) and Queensland (chi(311)2 = 1492.61; RMSEA =
.074; TLI = .80). While providing information of similar quality to that of the
original the abridged version is more efficient than the full scale.
PMID- 17037463
TI - Insomnia in relation to depression and somatic symptoms.
AB - A sample of 358 Kuwaiti volunteer college students responded to the Insomnia
Scale, the Somatic Symptoms Inventory, and the Center for Epidemiologic Studies
Depression Scale. The only significant sex difference was in somatic symptoms on
which women had a higher mean score than the men. Correlations between scores on
the Insomnia Scale and both Depression scales were .51 and .54 and for Somatic
Symptoms were .53 and .61 (p < .01) among men and women, respectively. The factor
analysis of the intercorrelations yielded a highly loaded general factor for
Psychological Disorder in both samples.
PMID- 17037465
TI - Psychological support for junior high school students: sibling order and sex.
AB - This study is a re-analysis of published data on psychological support for 609
junior high school students (317 boys, 292 girls, mean age = 14.1, SD = 0.8)
based on the self-report, Psychological Support Scale, to evaluate sibling order
as eldest or youngest and sex. In an earlier study, the questionnaire had been
modified to be applicable to junior high school students. The study re-examined
the data by extracting samples for categories of eldest and youngest siblings,
for re-analysis of self-reported psychological support by sibling order and sex.
Eldest children reported receiving more psychological support from both mother
and father than youngest. Also, eldest boys received significantly greater
psychological support from both the parents than the youngest boys or girls.
PMID- 17037464
TI - Prevalence of alcohol use by rural primary care outpatients in South Africa.
AB - In a primary care outpatient sample of 600 rural South Africans 37.4% of men and
10.7% of women were identified as hazardous drinkers, and 9.2% of men and 0.3% of
women met criteria for probable alcohol dependence or harmful drinking as defined
by AUDIT. Logistic multiple regression identified men and being single, divorced,
or widowed as predictors for hazardous and harmful drinking.
PMID- 17037466
TI - Association of race and color with mean IQ across nations.
AB - This study investigated the correlation of both race and skin color in the
distribution of mean IQ for 129 countries with primarily indigenous populations.
Skin color correlated most highly with mean IQ across the Caucasoid countries (r
= -.86), somewhat less across the Mongoloid countries (r = -.66), and
nonsignificantly across the Negroid countries (r = .06). When the Negroid and
Caucasoid countries were combined, both race and skin color yielded high
correlations with IQ (r = .87, -.95, respectively). When the Negroid and
Mongoloid countries were combined, both race and skin color yielded high
correlations with IQ (r = .91, -.91, respectively). When Caucasoid and Mongoloid
countries were combined, skin color yielded a high correlation, but race did not
correlate significantly with IQ. The greater importance of Negroid race was
regarded as congruent with the 1998 generalization of Jensen that the genetic
distance between Mongoloids and Caucasoid is less than the genetic distance of
these two groups from Negroid.
PMID- 17037467
TI - Autobiographical memories of televised sporting events watched in different
social settings.
AB - The present study asked 157 men and 154 women to recall their memories of viewing
both enjoyed and nonenjoyed televised sporting events from the past year in each
of four social circumstances: with friends, with family, with spouse,
boyfriend/girlfriend or significant other, and by oneself. For memories of all
eight events, participants were asked (1) the number and sex of coviewers, (2)
concurrent behaviors and cognitions engaged in while viewing, (3) uses and
gratifications sought for enjoyed events, and (4) failed uses and gratifications
for nonenjoyed events. Two analyses of variance, one full multiple regression,
and one step-wise regression were conducted. Analyses indicated that social
circumstance of viewing and sex of participant were associated with uses and
gratifications for enjoyed events, failed uses and gratifications for nonenjoyed
events, and concurrent behaviors and cognitions engaged in during the viewing.
Results are discussed in light of the uses and gratifications paradigm and Wenner
and Gantz's 1998 five fanship dimensions. An extension of this model to
nonenjoyed sporting events is proposed.
PMID- 17037468
TI - On structure of trauma-related stress reactions among people with diabetes
mellitus.
AB - The factorial structure of trauma-related stress reactions was explored using the
Purdue Posttraumatic Stress Disorder revised scale, in a sample of 106 adults
with insulin-dependent diabetes mellitus. An exploratory factor analysis yielded
2 factors, (a) arousal and passive cognitive-affective avoidance reactions and
(b) re-experiencing and active avoidance reactions. The 2-factor structure,
however, may also be reflective of the scale format which limits its
interpretative power.
PMID- 17037469
TI - Processes of inference, schizotypal thinking, and obsessive-compulsive behaviour
in a normal sample.
AB - Previous research has shown inferential confusion as measured by the Inferential
Confusion Questionnaire to be related to obsessive-compulsive symptoms. A total
of 108 participants (41 men and 66 women) from a normal population in The
Netherlands (M age = 46 yr., SD = 15.5) completed a package of questionnaires
measuring inferential confusion, schizotypal symptoms, and obsessive-compulsive
behaviour. As expected, scores for both inferential confusion and schizotypal
symptoms were significantly related to those for obsessive-compulsive behaviour.
In addition, analysis showed that inferential confusion and schizotypal symptoms
shared common variance, but both predicted an independent portion of the variance
in obsessive-compulsive behaviour while controlling for neuroticism. The present
results call for further inquiry into the role of inferential confusion and
schizotypal thinking in obsessive-compulsive behaviour.
PMID- 17037470
TI - Re-analysis of correlations among four impulsivity scales.
AB - Impulsivity plays a key role in normal and pathological behavior. Although there
is some consensus about its conceptualization, there have been many attempts to
build a multidimensional tool due to the lack of agreement in how to measure it.
A recent study claimed support for a three-dimensional structure of impulsivity,
however with weak empirical support. By re-analysing those data, a four-factor
structure was found to describe the correlation matrix much better. The debate
remains open and further research is needed to clarify the factor structure. The
desirability of constructing new measures, perhaps analogously to the Wechsler
Intelligence Scale, is emphasized.
PMID- 17037471
TI - Correlates of mood changes in obese women initiating a moderate exercise and
nutrition information program.
AB - This 20-wk. study assessed relationships of mean difference scores on measures of
self-efficacy and self-concept with scores for overall mood in 44 obese women who
initiated a moderate exercise and nutrition information program. Simultaneous
entry of changes in Physical Self-concept, Exercise Self-efficacy, and Body Areas
Satisfaction scale scores into a multiple regression equation explained a
significant 38% of the variance in changes in Total Mood Disturbance (R2 = .38,
F3,40 = 8.09, p < .001).
PMID- 17037472
TI - Correlates of low frustration tolerance in young adolescents.
AB - 148 young adolescents who reported low frustration tolerance also reported more
trait anger, state anger, and hostility.
PMID- 17037473
TI - Exact and resampling probability values for measures associated with ordered r by
c contingency tables.
AB - Permutation procedures to compute exact and resampling probability values
associated with measures of association for ordered r x c contingency tables are
described. Comparisons with asymptotic probability values demonstrated that exact
and resampling permutation procedures were preferred for sparse contingency
tables.
PMID- 17037474
TI - Factor structure of the Dysfunctional Attitude Scale (Form A) and the Automatic
Thoughts Questionnaire: an exploratory study.
AB - The factor structure of the Norwegian version of the Dysfunctional Attitude Scale
and the Automatic Thoughts Questionnaire was investigated with a sample of 344
male military recruits. Principal factor analyses with promax rotation indicated
four factors for the former, labeled Performance Evaluation, Need for Approval,
Autonomous Attitude, and Perfectionism which accounted for 15.5%, 3.6%, 2.6%, and
2.5% of the total variance, respectively. Two factors comprised the latter.
Factor 1 was labeled Negative Self-concept and Personal Maladjustment and
accounted for 40% of the total variance, and Factor 2 was labeled Desire for
Change and Negative Expectations and accounted for 6.3% of the total variance.
The findings may be useful in identifying the specific dysfunctional beliefs and
negative automatic thoughts exhibited by military recruits. Such information can
also contribute to the development of more effective treatment interventions.
PMID- 17037475
TI - Parental death and absence in children presenting for mental health care.
AB - Of 61 youth (M age 11.2 yr.) seeking mental health care, almost 60% had
experienced parental death or absence. 13 (21.3%) had experienced the death of a
parent during the preceding 3 years.
PMID- 17037476
TI - A measure of effect size for r x c contingency tables.
AB - Goodman and Kruskal's tau measure of categorical association is advanced as a
replacement for conventional measures of effect size for r x c contingency
tables. Goodman and Kruskal's tau is an asymmetric measure of categorical
association which is based entirely on the observed data and possesses a clear
interpretation in terms of proportional reduction in error. Comparisons with
conventional measures of effect size based on chi-squared such as Pearson's phi2,
Tschuprow's T2, and Cramer's V2 demonstrate the advantages of employing tau as a
measure of effect size.
PMID- 17037477
TI - Anxiety and depression in cataract surgery: a pilot study in the elderly.
AB - To assess anxiety induced by a planned cataract surgery and to evaluate the
correlations of rated anxiety and depression with optical acuity pre- and post
operatively, 278 patients ages 65 years or older were tested. Patients were
divided into two groups: first-eye and second-eye cataract surgery. Anxiety and
depression were evaluated using the Hamilton's Rating Scales for Anxiety and
Depression, respectively. Pre-operatively, first-eye patients showed
significantly higher anxiety than second-eye patients (F1,251 = 75.39, p < .001).
First-eye patients rated peak anxiety on the day of the surgery, while patients
scheduled for second-eye cataract surgery presented no fluctuations in rated
anxiety (F1,251 = 49.60, p < .001). There was no correlation of preoperative
anxiety or depression with the outcome of surgery (F(1,251)s = .83 and .58,
respectively, p > .05). Postoperatively, anxiety and depression in patients
without any improvement in their vision were rated significantly higher than in
those presenting improved visual acuity after surgery (F1,251 = 566.17 and
300.25, respectively, p < .001).
PMID- 17037478
TI - Attitude toward Christianity and paranormal belief among 13- to 16-yr.-old
students.
AB - A small but statistically significant positive correlation (r = .17) was found in
a sample of 279 13- to 16-yr.-old students in Wales between scores on the Francis
Scale of Attitude toward Christianity and on a new Index of Paranormal Belief.
These data suggest that there is little common variance between attitude toward
Christianity and belief in the paranormal.
PMID- 17037479
TI - Factor analysis to examine psychometric properties of family functioning
measures.
AB - To assess the relationship of family functioning to problem behaviors and alcohol
and drug use among youth, researchers must test the effects of interventions
using suitably constructed and psychometrically sound scales. This study
evaluated whether originally calculated coefficients alpha underestimate the
reliability of the family functioning measures given. Through exploratory factor
analysis, estimates of alternative internal consistency reliability which might
improve the estimate of reliability were examined. Responses of 755 adults from
Strengthening Multi-ethnic Families and Communities were analyzed. Coefficients
alpha for two scales were modest (alpha = .68 and alpha = .75), and factor
analysis indicated that the scales were multidimensional. After exploratory
factor analysis, the reassessment of reliability based on the extracted factors
indicated an overall increase in the coefficients alpha.
PMID- 17037480
TI - Cultural differences and economic development of 31 countries.
AB - To update and extend the empirical research of Hofstede, the influence of culture
on 31 nations' economic development was examined and support for modernization
theory provided. Per capita gross domestic product, literacy rates, the negative
of the population growth rate, and life expectancy development data were
collected from 31 countries. The pattern of correlations among measures provided
partial support for Hofstede's 1980 findings.
PMID- 17037481
TI - Personality traits and university program.
AB - Participants were 147 undergraduates majoring in programs classified as more
professional (education, n = 28; business, n = 33) or less professional (natural
sciences, n = 36; social science, n = 50) and more people-oriented (education,
social sciences) or less people-oriented (business, natural sciences). They
completed self-report tests for 13 personality constructs (five from Goldberg's
version of the Five Factor Model, three from Eysenck and Eysenck's theory, and
five others). Students in less professional disciplines scored higher on openness
to experience (intellect/imagination) than those in more professional
disciplines. Students in more people-oriented disciplines scored higher on
empathy than those in less people-oriented disciplines. Women scored higher than
men on conscientiousness, industriousness, and empathy, but lower than men on
independence. Critical comments are offered and suggestions for research are
made.
PMID- 17037482
TI - Personality and attitude toward Christianity among churchgoers: a replication.
AB - A sample of 158 churchgoers attending eight Anglican churches in the United
Kingdom completed the abbreviated Revised Eysenck Personality Questionnaire
together with the Francis Scale of Attitude toward Christianity to replicate a
1996 study by Carter, Kay, and Francis. Data confirm that scores on Attitude
toward Christianity were significantly negatively related to Psychoticism, but to
neither Extraversion nor Neuroticism scores.
PMID- 17037483
TI - Acculturation and suicide attitudes: a study of perceptions about suicide among a
sample of Ghanaian immigrants in the United States.
AB - To investigate whether a relationship exists between acculturation and attitudes
about suicide, 81 Ghanaian immigrants living in the U.S. who responded to a mail
inquiry were selected to participate in the current study. This particular
immigrant sample was chosen because although they represent a rapidly growing
group in the U.S., they have been rarely studied. Respondents consisted of 42
women and 36 men (3 did not identify their sex), with a mean age of 29.5 yr. (SD
= 10.6). Participants completed measures of acculturation and attitudes about
suicide. Results indicated significant correlations between length of residency
in the United States and negative suicide attitudes, and also between
psychological acculturation and negative suicide attitudes. No significant
relationship was found between behavioral acculturation and suicide attitudes.
Furthermore, length of residency was a stronger predictor of suicide attitudes
than other subjective measures of acculturation. Implications and suggestions for
further research are discussed.
PMID- 17037484
TI - Absolutism in diaries of suicides.
AB - Two diaries, one from a completed suicide and one from an attempted suicide, were
examined for the use of three words indicating absolutist thinking (perfect,
always, and never). The diary of the attempted suicide had a significantly higher
frequency use of "never" (2.75 per 1,000 words versus 1.73) but not the other
words.
PMID- 17037485
TI - "Self-execution" and state execution.
AB - In the United States from 1977 to 1999, the suicide rate of death row inmates was
not associated with their probability of execution (r = -.25).
PMID- 17037486
TI - The metaphysical nuances of hylomorphism.
PMID- 17037487
TI - A critique of oocyte-assisted reprogramming.
PMID- 17037488
TI - Bibliography of secondary sources on the history of dermatology II. Obituaries
and biographies in English supplemented through 2005 [corrected].
PMID- 17037489
TI - Chimeras: from poetry to science.
PMID- 17037490
TI - An overview of chimeras and hybrids.
PMID- 17037491
TI - The strange case of the humanzee patent quest.
PMID- 17037492
TI - How to navigate boundaries: a reply to The American Journal of Bioethics.
PMID- 17037493
TI - Considering chimeras: the confluence of genetic engineering and ethics.
PMID- 17037494
TI - Human brain cells in animal brains: philosophical and moral considerations.
PMID- 17037495
TI - Is it ethical to generate human-animal chimeras?
PMID- 17037496
TI - Catholic teaching on the human embryo as an object of research.
PMID- 17037497
TI - The coronavirus replicase: insights into a sophisticated enzyme machinery.
PMID- 17037498
TI - Biochemical aspects of coronavirus replication.
PMID- 17037499
TI - A previously unrecognized UNR stem-loop structure in the coronavirus 5'
untranslated region plays a functional role in replication.
PMID- 17037500
TI - Regulation of coronavirus transcription: viral and cellular proteins interacting
with transcription-regulating sequences.
PMID- 17037501
TI - Deubiquitinating activity of the SARS-CoV papain-like protease.
PMID- 17037502
TI - Nucleocapsid protein expression facilitates coronavirus replication.
PMID- 17037503
TI - Non structural proteins 8 and 9 of human coronavirus 229E.
PMID- 17037504
TI - Effects of mutagenesis of murine hepatitis virus nsp1 and nsp14 on replication in
culture.
AB - For nsp1, the fact that the carboxy-terminal but not the amino-terminal half of
the protein can be deleted suggests that there may be specific and distinct
domains within the protein or that the entire protein is dispensable but that the
RNA encoding the amino-terminal half of nsp1 cannot be deleted. The
identification of specific required residues support the conclusion that it is
the portion of the protein that is required for replication. The results of
mutagenesis of the nsp14 coding region and flanking cleavage sites also provided
important new insights into this protein and its requirements. Our previous study
raised the question as to the essential nature of nsp14 in replication. The
results of this study show that putative active site residues cannot be
substituted without loss of replication in culture. Interestingly, mutagenesis of
Tyr414 showed that while this residue can tolerate a number of substitutions, it
was intolerant of Lysine or deletion. The results suggest that nsp14 is required
for replication. However, whatever functions nsp14 serves appear to be retained
by noncleaved or partially processed nsp14, since abolition of either the amino
terminal or carboxy-terminal cleavage site allowed recovery of viable virus.
PMID- 17037505
TI - Mutational analysis of MHV-A59 replicase protein-nsp10.
PMID- 17037506
TI - The nsp2 proteins of mouse hepatitis virus and SARS coronavirus are dispensable
for viral replication.
AB - The results presented here demonstrate that the MHV and SARS-CoV nsp2 proteins
are not required for the production of infectious virus, for polyprotein
expression or processing, or for viral replication complex formation in cell
culture. The nsp2 protein domain resides in a region of the coronavirus replicase
that is relatively nonconserved across coronaviruses. In fact, the size and amino
acid sequence variability of nsp2 across the different coronaviruses has led some
investigators to speculate that the nsp2 protein, along with the nsp1 and nsp3
proteins, may play host- and/or cell-specific roles in the virus life cycle.
While this may be the case, it should be noted that nsp2, in some form, exists in
all coronaviruses studied to date and likely plays a pivotal role in the viral
life cycle. A previous study from our laboratory identified a coronavirus
replicase protein that plays an important role in viral pathogenesis. Such may
prove to be the case for nsp2, as well. Alternatively, beacuse nsp2 exists as a
detectable precursor protein nsp2-3 prior to processing of nsp2 and nsp3 into
mature proteins, nsp2 may play a critical adaptor/regulatory role for nsp3
function. Importantly, the viruses produced in this study provide a system by
which the role of the nsp2 protein in viral infection can be characterized.
PMID- 17037507
TI - Molecular dissection of porcine reproductive and respiratory virus putative
nonstructural protein 2.
PMID- 17037508
TI - Differential role of N-terminal polyprotein processing in coronavirus genome
replication and minigenome amplification.
PMID- 17037509
TI - Identification and characterization of severe acute respiratory syndrome
coronavirus subgenomic RNAs.
PMID- 17037510
TI - Identification and characterization of a unique ribosomal frameshifting signal in
SARS-CoV ORF3a.
PMID- 17037511
TI - ADP-ribose-1"-phosphatase activities of the human coronavirus 229E and SARS
coronavirus X domains.
PMID- 17037512
TI - Nonstructural proteins of human coronavirus NL63.
PMID- 17037513
TI - MHV-A59 ORF1a replicase protein nsp7-nsp10 processing in replication.
PMID- 17037514
TI - Stem-loop 1 in the 5' UTR of the SARS coronavirus can substitute for its
counterpart in mouse hepatitis virus.
PMID- 17037515
TI - Transcriptional regulation of RNA3 of infectious bronchitis virus.
PMID- 17037516
TI - Structure, expression, and intracellular localization of the SARS-CoV accessory
proteins 7a and 7b.
PMID- 17037517
TI - Sumoylation of the nucleocapsid protein of severe acute respiratory syndrome
coronavirus by interaction with Ubc9.
PMID- 17037518
TI - Importance of MHV-CoV A59 nucleocapsid protein COOH-terminal negative charges.
PMID- 17037519
TI - Expression and structural analysis of infectious bronchitis virus nucleoprotein.
PMID- 17037520
TI - Mouse hepatitis virus infection activates the Ire1/XBP1 pathway of the unfolded
protein response.
PMID- 17037521
TI - The nuclear localization signal of the PRRS virus nucleocapsid protein viral
replication in vitro and antibody response in vivo.
PMID- 17037522
TI - SARS coronavirus accessory ORFs encode luxury functions.
PMID- 17037523
TI - Production and characterization of monoclonal antibodies against the nucleocapsid
protein of SARS-CoV.
PMID- 17037524
TI - Mouse hepatitis coronavirus nucleocapsid phosphorylation.
PMID- 17037525
TI - Genetic and molecular biological analysis of protein-protein interactions in
coronavirus assembly.
PMID- 17037526
TI - New insights on the structure and morphogenesis of Berne virus.
PMID- 17037527
TI - Ultrastructure of SARS-CoV, FIPV, and MHV revealed by electron cryomicroscopy.
PMID- 17037529
TI - The transmembrane domain of the infectious bronchitis virus E protein is required
for efficient virus release.
PMID- 17037528
TI - Role of mouse hepatitis coronavirus envelope protein transmembrane domain.
PMID- 17037530
TI - Viroporin activity of SARS-CoV E protein.
PMID- 17037531
TI - Efficient transduction of dendritic cells using coronavirus-based vectors.
PMID- 17037532
TI - Insights from the association of SARS-CoV S-protein with its receptor, ACE2.
PMID- 17037533
TI - Attachment factor and receptor engagement of SARS coronavirus and human
coronavirus NL63.
PMID- 17037534
TI - Interactions between SARS coronavirus and its receptor.
PMID- 17037535
TI - Proteolysis of SARS-associated coronavirus spike glycoprotein.
PMID- 17037536
TI - Fluorescence dequenching assays of coronavirus fusion.
PMID- 17037537
TI - Porcine arterivirus entry in macrophages: heparan sulfate-mediated attachment,
sialoadhesin-mediated internalization, and a cell-specific factor mediating virus
disassembly and genome release.
PMID- 17037538
TI - Enhancement of SARS-CoV infection by proteases.
PMID- 17037539
TI - Increased viral titers and subtle changes in plaque morphology upon passage of
SARS-CoV in cells from different species.
PMID- 17037540
TI - Human coronavirus 229E can use CD209L (L-SIGN) to enter cells.
PMID- 17037541
TI - Intracellular transport of the S proteins of coronaviruses.
PMID- 17037542
TI - Analysis of SARS-CoV receptor activity of ACE2 orthologs.
PMID- 17037543
TI - Interaction between the spike protein of human coronavirus NL63 and its cellular
receptor ACE2.
PMID- 17037544
TI - Human angiotensin-converting enzyme 2 (ACE2) is a receptor for human respiratory
coronavirus NL63.
PMID- 17037545
TI - Molecular interactions of group 1 coronaviruses with feline APN.
PMID- 17037546
TI - Pseudotyped vesicular stomatitis virus for functional analysis of SARS
coronavirus spike protein.
PMID- 17037547
TI - Subcellular localization of SARS-CoV structural proteins.
PMID- 17037548
TI - Spike gene determinants of mouse hepatitis virus host range expansion.
PMID- 17037549
TI - Virion-liposome interactions identify a cholesterol-independent coronavirus entry
stage.
PMID- 17037551
TI - Three-dimensional reconstruction of the nucleolus using meta-confocal microscopy
in cells expressing the coronavirus nucleoprotein.
PMID- 17037550
TI - Avian infectious bronchitis virus enters cells via the endocytic pathway.
PMID- 17037552
TI - Dissection of the fusion machine of SARS-coronavirus.
PMID- 17037553
TI - Characterization of persistent SARS-CoV infection in Vero E6 cells.
PMID- 17037554
TI - Receptor-independent spread of a neurotropic murine coronavirus MHV-JHMV in mixed
neural culture.
PMID- 17037555
TI - Receptor-independent infection of mouse hepatitis virus: analysis by
spinoculation.
PMID- 17037556
TI - SARS-CoV, but not HCoV-NL63, utilizes cathepsins to infect cells: viral entry.
PMID- 17037557
TI - Coronavirus immunity: from T cells to B cells.
PMID- 17037558
TI - Rat coronavirus infection of primary rat alveolar epithelial cells.
PMID- 17037559
TI - Infectious bronchitis coronavirus induces cell-cycle perturbations.
PMID- 17037560
TI - Genes 3 and 5 of infectious bronchitis virus are accessory protein genes.
PMID- 17037561
TI - NKG2D signaling and host defense after mouse hepatitis virus infection of the
central nervous system.
PMID- 17037562
TI - Murine hepatitis virus strain 1 as a model for severe acute respiratory distress
syndrome (SARS).
PMID- 17037563
TI - Persistent coronavirus infection of progenitor oligodendrocytes.
PMID- 17037564
TI - CD8+ T-cell priming during a central nervous system infection with mouse
hepatitis virus.
PMID- 17037565
TI - Antibody-mediated virus clearance from neurons of rats infected with
hemagglutinating encephalomyelitis virus.
PMID- 17037566
TI - Developing bioinformatic resources for coronaviruses.
PMID- 17037567
TI - Autoantibodies exacerbate the severity of MHV-induced encephalitis.
PMID- 17037568
TI - Analysis of the N protein in feline coronavirus strains in Italy.
PMID- 17037569
TI - Differential induction of proinflammatory cytokines in primary mouse astrocytes
and microglia by coronavirus infection.
PMID- 17037570
TI - Preferential infection of mature dendritic cells by the JHM strain of mouse
hepatitis virus.
PMID- 17037571
TI - Role of the replicase gene of murine coronavirus JHM strain in hepatitis.
PMID- 17037572
TI - Identification of the receptor for FGL2 and implications for susceptibility to
mouse hepatitis virus (MHV-3)-induced fulminant hepatitis.
PMID- 17037573
TI - Equine viral arteritis.
AB - EVA is an important if uncommon disease of horses. Potential economic losses
attributable to EVA include direct losses from abortion, pneumonia in neonates,
and febrile disease in performance horses. Indirect losses are those associated
with national and international trade/animal movement regulations, particularly
those pertaining to persistently infected carrier stallions and their semen.
However, EAV infection and EVA are readily prevented through serological and
virological screening of horses, coupled with sound management practices that
include appropriate quarantine and strategic vaccination.
PMID- 17037574
TI - Use of a PRRSV infectious clone to evaluate in vitro quasispecies evolution.
PMID- 17037575
TI - Gamma-interferon involvement in the pathogenesis of lactate dehydrogenase
elevating virus infection.
PMID- 17037576
TI - Replication and expression analysis of PRRSV defective RNA.
PMID- 17037577
TI - Efficacy of an inactivated PRRSV vaccine: induction of virus-neutralizing
antibodies and partial virological protection upon challenge.
PMID- 17037578
TI - SARS and other coronaviruses in humans and animals.
PMID- 17037579
TI - Animal models for SARS.
PMID- 17037580
TI - HCoV-OC43-induced apoptosis of murine neuronal cells.
PMID- 17037581
TI - Infection of human airway epithelia by SARS coronavirus is associated with ACE2
expression and localization.
PMID- 17037582
TI - Human coronavirus NL63 infection is associated with croup.
PMID- 17037583
TI - A SARS-CoV-specific protein enhances virulence of an attenuated strain of mouse
hepatitis virus.
PMID- 17037584
TI - Genetic evolution of human coronavirus OC43 in neural cell culture.
PMID- 17037585
TI - Synergistic inhibition of SARS-coronavirus replication by type I and type II IFN.
PMID- 17037586
TI - Mustela vison ACE2 functions as a receptor for SARS-coronavirus.
PMID- 17037587
TI - HCoV-229E infects and activates monocytes.
PMID- 17037589
TI - Identification of ferret ACE2 and its receptor function for SARS-coronavirus.
PMID- 17037588
TI - Pathological and virological analyses of severe acute respiratory syndrome
associated coronavirus infections in experimental animals.
PMID- 17037590
TI - Human coronavirus-NL63 infection is not associated with acute Kawasaki disease.
PMID- 17037591
TI - Toward the development of an infectious cDNA clone of a human enteric
coronavirus.
PMID- 17037592
TI - HCoV-OC43-induced encephalitis is in part immune-mediated.
PMID- 17037593
TI - SARS CoV replication and pathogenesis in human airway epithelial cultures.
PMID- 17037594
TI - Immunogenicity of SARS-CoV: the receptor-binding domain of S protein is a major
target of neutralizing antibodies.
PMID- 17037595
TI - Glia expression of MHC during CNS infection by neurotropic coronavirus.
PMID- 17037596
TI - Resurrection of an "extinct" SARS-CoV isolate GD03 from late 2003.
PMID- 17037597
TI - SARS coronavirus vaccine development.
PMID- 17037598
TI - Development of vaccines and passive immunotherapy against SARS coronavirus using
mouse and SCID-PBL/hu mouse models.
AB - We have investigated novel vaccines strategies against severe acute respiratory
syndrome (SARS) CoV infection using cDNA constructs encoding the structural
antigens; spike (S), membrane (M), envelope (E), or nucleocapsid (N) protein,
derived from SARS CoV (strain HKU39849, TW1, or FFM-1). As SARS-CoV is thought to
infect the alveolar epithelial cell of the lung,in the present study, a type II
alveolar epithelial cell clone, T7, was used to analyze the mechanism of CTL
against SARS CoV membrane antigens. Mice vaccinated with SARS CoV (N) DNA or (M)
DNA using pcDNA 3.1 (+) plasmid vector showed T-cell immune responses (CTL
induction and proliferation) against type II alveolar epithelial cells (T7)
transfected with SARS (N) or (M) DNA, respectively. To determine whether these
DNA vaccines could induce T-cell immune responses in humans as well as in mice,
SCID-PBL/hu mice were immunized with these DNA vaccines. PBL from healthy human
volunteers were administered i.p. into IL-2 receptor gamma-chain-disrupted NOD
SCID mice [IL-2R(-/-) NOD-SCID]. SCID-PBL/hu mice thus constructed can be used to
analyze the human immune response in vivo. The SCID-PBL/hu mice were immunized
with SARS (N) DNA or (M) DNA and analyzed for a human T-cell immune response. The
M DNA vaccine enhanced CTL activity and proliferation in the presence of M
peptide in SCID-PBL/hu mice. Furthermore, the SARS N DNA vaccine induced CTL
activity (IFN-gamma production by recombinant N protein or N protein-pulsed
autologous B blast cells) and proliferation of spleen cells in SCID-PBL/hu mice.
These results, demonstrate that SARS M and N DNA vaccines induced human CTL and
human T-cell proliferative responses. On the other hand, we have developed SARS
DNA vaccines that induce human neutralizing antibodies and human monoclonal
antibodies against SARS CoV. Transgenic mice expressing SARS-CoV receptor
(angiotensin converting enzyme 2) are also under development. These vaccines are
expected to induce immune responses specific for SARS CoV in human and should
provide useful tool for development of protective vaccines.
PMID- 17037599
TI - Inhibition and escape of SARS-CoV treated with antisense morpholino oligomers.
PMID- 17037600
TI - Validation of coronavirus E proteins ion channels as targets for antiviral drugs.
PMID- 17037601
TI - Identification of essential genes as a strategy to select a SARS candidate
vaccine using a SARS-CoV infectious cDNA.
PMID- 17037602
TI - Structure and dynamics of SARS coronavirus main proteinase (Mpro).
PMID- 17037603
TI - Highly attenuated vaccinia virus DIs as a potential SARS vaccine.
PMID- 17037604
TI - Renilla luciferase as a reporter to assess SARS-CoV mRNA transcription regulation
and efficacy of anti-SARS-CoV agents.
PMID- 17037605
TI - Virucidal effect of a newly developed nickel alloy on mouse coronavirus.
PMID- 17037606
TI - Construction of a full-length cDNA infectious clone of a European-like Type 1
PRRSV isolated in the U.S.
PMID- 17037608
TI - To an athlete, aching young.
PMID- 17037607
TI - Identification and evaluation of coronavirus replicase inhibitors using a
replicon cell line.
PMID- 17037609
TI - Test strategies in bovine viral diarrhea virus control and eradication campaigns
in Europe.
AB - Several European countries have initiated national and regional control-and
eradication campaigns for bovine viral diarrhea virus (BVDV). Most of these
campaigns do not involve the use of vaccines; in Germany, vaccination is used
only in states in which it is considered necessary because of high BVDV
prevalence. In European countries without organized BVDV control programs,
vaccination is commonly used to control BVDV. Diagnostic test strategies are
fundamental to all control-and-eradication campaigns; therefore, the purpose of
this review is to describe how the available diagnostic tests are combined into
test strategies in the various phases of control-and-eradication campaigns in
Europe. Laboratory techniques are available for BVDV diagnosis at the individual
animal level and at the herd level. These are strategically used to achieve 3
main objectives: 1) initial tests to classify herd status, 2) follow-up tests to
identify individual BVDV-infected animals in infected herds, and 3) continued
monitoring to confirm BVDV-free status. For each objective or phase, the validity
of the diagnostic tests depends on the mode of BVDV introduction and duration of
infection in test-positive herds, and on how long noninfected herds have been
clear of BVDV. Therefore, the various herd-level diagnostic tools--such as
antibody detection in bulk milk or in blood samples from young stock animals, or
BVDV detection in bulk milk--need to be combined appropriately to obtain
effective strategies at low cost. If the individual diagnostic tests are used
with due consideration of the objectives of a specific phase of a BVDV control
program, they are effective tools for controlling and eradicating BVDV in regions
not using vaccination and where vaccination is a part of the control or
eradication program.
PMID- 17037610
TI - Detection of antibodies in serum and egg yolk following infection of chickens
with an H6N2 avian influenza virus.
AB - Active serologic surveillance programs to detect avian influenza viruses (AIVs)
in table egg-laying chickens have been initiated by several states as a response
to the economic threat posed by these viruses. Most outbreaks of avian influenza
in domestic poultry are caused by mildly pathogenic AIVs. In the study reported
here, infection by an H6N2 AIV was used as a model of mildly pathogenic AIV
infections in egg-type chickens. The total number of eggs laid by 5 control hens
was 619 or 0.904 eggs/day/hen, whereas the total number laid by 10 infected hens
was 1,018 or 0.743 eggs/day/hen. The difference in egg production between the 2
groups was not statistically significant (P = 0.38). Anti-influenza antibodies
were monitored by use of an agar gel immunodiffusion test and an ELISA for a
period of 20 weeks after inoculation. Antibodies in serum developed sooner,
peaked at higher levels, and remained at higher levels than did antibodies found
in egg yolk, as indicated by ELISA results. For infected chickens, the
correlation between serum and egg yolk ratios was 0.66. Serum samples would
appear to be preferable to egg yolk samples for surveillance programs intended to
identify chicken flocks that may have been infected by an AIV weeks or months
before samples are collected.
PMID- 17037611
TI - Determination of sheep prion gene polymorphisms from paraffin-embedded tissue.
AB - Amino acid polymorphisms of the prion protein (PrP) greatly influence the
susceptibility of sheep to scrapie. Selective breeding to increase the prevalence
of PrP gene alleles associated with scrapie resistance is a flock management
practice that is important for scrapie control programs. Determination of sheep
PrP alleles typically has required extraction of DNA from host tissues that are
freshly derived or stored frozen. We describe application of a DNA extraction
procedure for formalin-fixed, paraffin-embedded tissues (PET) for the purpose of
PCR amplification and nucleotide sequencing of relevant codons (136-171) of the
sheep PrP gene. Tissues derived from 96 sheep were studied. The DNA sequence
identity was confirmed in 87 of 94 matched samples of PET and frozen tissue
specimens. DNA from brainstem PET of 2 sheep, from which fresh tissue was not
available, was amplified and sequenced after formalin fixation for 7-70 days.
This method will allow retrospective analysis of PrP genetics of sheep subsequent
to postmortem diagnosis of scrapie when nonfixed tissue is unavailable for DNA
extraction; however, it is not recommended that submission of fixed tissue
supplant collection of fresh tissues for the purpose of determining PrP gene
polymorphisms.
PMID- 17037612
TI - Comparison of milk and serum enzyme-linked immunosorbent assays for diagnosis of
Mycobacterium avium subspecies paratuberculosis infection in dairy cattle.
AB - Milk and serum samples from 35 dairy herds in 17 states were evaluated for cow-
and herd-level Mycobacterium avium subspecies paratuberculosis (MAP) antibody
test agreement. Evaluation of 6,349 samples suggested moderate agreement between
milk and serum enzyme-linked immunosorbent assay (ELISA) results, with a kappa
value of 0.50. Cow-level sensitivity (Se) for 18 dairy operations with 1,921
animals was evaluated relative to fecal culture results. At the cow level, the
milk ELISA relative Se was not significantly different from that of the serum
ELISA (21.2 and 23.5%, respectively). Logistic regression models revealed a
positive association between lactation number and milk ELISA status. Non-Holstein
cows were more likely to test milk ELISA positive than Holstein cows. Cows in the
first 2 weeks of lactation and after week 45 of lactation were more likely to
test milk ELISA positive than cows between 3 and 12 weeks of lactation. Milk
production > 80% of herd average was negatively associated with testing milk
ELISA positive. Animals in the West and Midwest regions were less likely than
animals in the Southeast region to test ELISA positive by either test. Estimates
for herd-level sensitivity for the milk and serum ELISA, relative to fecal
culture results, ranged from 56 to 83%. At the cow and herd levels, milk ELISA
performed equivalent to serum ELISA using fecal culture as a reference for MAP
infection and has the advantage of decreased labor costs on farms that use Dairy
Herd Improvement Association testing.
PMID- 17037613
TI - A new fluorogenic real-time RT-PCR assay for detection of lineage 1 and lineage 2
West Nile viruses.
AB - West Nile virus represents an emerging threat for animal and human health
worldwide. This virus exhibits a marked genetic variation, with at least 2
distinct evolutionary lineages. Lineage 1 has been recognized in Africa, Asia,
Europe, Oceania, and more recently in the Americas, whereas lineage 2 is
restricted to Africa. Perhaps for this reason, the available real-time RT-PCR
methods for detecting West Nile virus genome have mainly focused on lineage 1.
However, both viruses may potentially be spread beyond their endemic areas by
migratory birds. This report describes a new real-time reverse transcription-PCR
(RT-PCR) method based on a 5'-Taq nuclease-3' minor groove binder DNA probe
(TaqMan MGB) that allows the detection of a wide range of West Nile virus
isolates, including both lineages 1 and 2. This method was able to detect West
Nile viruses from different origins (North and Central Africa, Middle East,
Europe, and North America), whereas other flaviviruses (Usutu, Dengue, Yellow
fever) analyzed in parallel remained negative. The sensitivity achieved by this
assay was 10(-2)-10(-3) pfu/tube. This method, which can be performed in 96-well
format, could be suitable for the large-scale surveillance of West Nile virus in
areas where both lineages can potentially spread.
PMID- 17037614
TI - Detection of hepatitis E virus shedding in feces of pigs at different stages of
production using reverse transcription-polymerase chain reaction.
AB - The aim of this study was to determine at which production stages hepatitis E
virus (HEV) is shed by the highest number of pigs and to estimate the relative
risk associated with each stage. For this purpose, 146 fecal samples of pigs from
21 farms were studied. In addition, 1 sample from the manure ditch and another
sample of drinking water, collected directly from the trough located in the pen,
were taken from 16 farms. HEV RNA was detected in fecal samples from 34 pigs
(23.29%). The production stages in which most pigs excreted HEV were weaners
(41.7%) and pigs in the first month of feeding (60%). The results of the
statistical analysis showed that the principal significant risk stage in HEV
shedding was the first month of feeding (odds ratio [OR] 19.5, 95% CI 3.59
106.07, P = 0.001) followed by the weaners stage (OR 9.3, 95% CI .78-48.42, P =
0.008). In 8 out of 16 farms tested (50%) HEV RNA was detected in raw manure and
in the water trough of only 1. Detection of HEV in manure ditches raises the
concern of how to deal with manure of swine origin, because it is used as soil
fertilizer.
PMID- 17037615
TI - Effect of hemolysis on nonesterified fatty acid and beta-hydroxybutyrate
concentrations in bovine blood.
AB - Nonesterified fatty acid (NEFA) and beta-hydroxybutyrate (BHB) assays are used
for evaluating dairy herds for negative energy balance and subclinical ketosis,
respectively. Hemolysis is a common artifact in samples submitted to diagnostic
laboratories. The effect of hemolysis on NEFA and BHB in bovine serum was
determined. Hemolysis was introduced into 26 serum samples by adding serial
dilutions of a red cell hemolysate, prepared by repeated freeze-thawing of EDTA
anticoagulated bovine blood. NEFA, BHB, and degree of hemolysis (hemolytic index)
were measured by an automated chemistry analyzer. Two endpoint assays that
differed by inclusion of a sample blank were used for NEFA measurement. A kinetic
enzymatic assay with 2 reagent sources was used for BHB measurement. The assessed
methods yielded similar NEFA or BHB results in baseline, nonhemolyzed samples
(median NEFA: 0.25 mEq/L, median BHB: 3 mg/dL, median hemolytic index: 8 units).
NEFA results were adversely affected by hemolysis, with values increasing
significantly with higher degrees of hemolysis. Median values increased above a
critical medical decision limit (0.40 mEq/L) at a hemolytic index of 506 units
(marked hemolysis). This increase was prevented by inclusion of a sample blank.
Result interpretation was affected in individual animals when samples were
moderately hemolyzed (median hemolytic index: 258 units). In contrast, BHB
results were unaffected by hemolysis with either reagent source. Thus, assays for
measuring NEFAs should include a sample blank and NEFA results should not be
interpreted in moderately to markedly hemolyzed bovine samples, because result
accuracy cannot be assured.
PMID- 17037616
TI - Comparison of cytogenetics and polymerase chain reaction based detection of the
amelogenin gene polymorphism for the diagnosis of freemartinism in cattle.
AB - A polymerase chain reaction (PCR) assay which detects a sex-based polymorphism in
the bovine amelogenin locus was modified and compared to conventional cytogenetic
analysis for diagnosis of freemartinism (XX/XY chimerism) in cattle. The PCR
assay is more sensitive than cytogenetic analysis for detection of XY cells, with
the limit of detection of the assay falling between 0.2% and 1% XY cells. Seventy
three heifer blood samples submitted for evaluation of freemartinism to the
University of Minnesota Diagnostic Laboratory were tested using both cytogenetic
and PCR techniques. Poor-quality samples precluded successful lymphocyte culture
and recovery of mitotic nuclei for cytogenetic evaluation in 17 cases (23%). Two
of these samples (2.7%) also failed to amplify with PCR. There was 100% agreement
in the results from the 56 samples that were suitable for testing using both
techniques. This PCR-based assay provides an alternative to the more laborious
cytogenetic evaluation for diagnosis of freemartinism.
PMID- 17037617
TI - Isolation of equine herpesvirus-5 from blood mononuclear cells of a gelding.
AB - Horses are commonly infected by herpesviruses, but isolation of equine
herpesvirus-5 (EHV-5) has only infrequently been reported. We describe the
isolation and characterization of a strain of EHV-5 from the blood mononuclear
cells of a healthy adult horse in California. The virus was initially identified
by EHV-5 specific polymerase chain reaction (PCR), and it caused lytic infection
of cultured rabbit kidney cells only after repeated serial passage. Virions with
characteristic herpesvirus morphology were readily demonstrated in cell culture
lysate by transmission electron microscopy. A portion of the glycoprotein B gene
of this strain of EHV-5 had 99% identity to the published EHV-5 sequence, and it
was clearly distinguishable from other EHV (1-4) by virus-specific PCR assays.
Prevalence of EHV-5 infection in a group of young racehorses was estimated at 64%
using the EHV-5 specific PCR on nasopharyngeal secretions.
PMID- 17037619
TI - Distribution of equine infectious anemia in horses in the north of Minas Gerais
State, Brazil.
AB - The paper examines the prevalence of equine infectious anemia (EIA) in horse
populations in the northern part (comprising 89 cities) of Minas Gerais State,
Brazil, from January 2002 to December 2004. Data on 8,981 agar gel
immunodiffusion test results from the region were used as input for a statistical
and autoregressive analysis model to construct a city-level map of the
distribution of EIA prevalence. The following EIA prevalence (P) levels were
found: 49 cities with 0 < P < or = 0.5%, 26 with 0.5% < P < or = 1.5%, 10 with
1.5% < P < or = 5%, and 4 with 5% < P < or = 25%.
PMID- 17037618
TI - Goat paratuberculosis in Chile: first isolation and confirmation of Mycobacterium
avium subspecies paratuberculosis infection in a dairy goat.
AB - In October 2004, 41 goats > 2 years old from a Saanen dairy goat herd located in
Purranque County, 10th Region, Chile, were sampled and tested for
paratuberculosis. While collecting samples it was observed that several goats
were thin and emaciated. One goat was sufficiently debilitated to warrant humane
euthanasia. This animal was brought to the Veterinary School at the Universidad
Austral de Chile for necropsy. The goat selected for necropsy was a 12-year-old
doe. The animal showed classical clinical signs of caprine paratuberculosis:
emaciation despite willingness to eat, dry and rough hair coat, and no evidence
of diarrhea. Gross pathology and histopathology of the necropsied goat were
consistent with paucibacillary paratuberculosis. Bacteriology, serology, and PCR
confirmed the diagnosis. This is the first published report of goat
paratuberculosis in Chile confirming a case of caprine paucibacillary
paratuberculosis.
PMID- 17037620
TI - Chlorophacinone exposure causing an epizootic of acute fatal hemorrhage in lambs.
AB - This report describes an epizootic of chlorophacinone toxicosis in lambs with
severe acute hemorrhages. Eleven lambs, approximately 1-2 months of age, suddenly
developed epistaxis, respiratory distress, and facial and cervical swelling.
Affected animals died within 1-2 hours from the onset of clinical signs. Two
lambs were available for complete postmortem examination. Gross lesions included
mucosal and organ pallor, icterus, melena, and lung edema, as well as thymic,
cervical muscle, and intra-articular hemorrhage. Histologically hepatocellular
centrolobular necrosis was observed. The anticoagulant chlorophacinone was
detected in the livers at 0.58 ppm and 0.50 ppm (wet weight), respectively. The
source of exposure to chlorophacinone was old bait material placed between the
wall studs of the building housing the ewes and lambs. The lambs were able to
reach the bait through a hole in the plywood interior wall of the building.
PMID- 17037621
TI - Acute anhydrous ammonia intoxication in cattle.
AB - Intoxication with anhydrous ammonia (AA) is a common occupation-related health
problem affecting farmers and fertilizer applicators, however, very few
descriptions of animal exposure to this toxicant exist. Thieves entered a feedlot
and damaged a liquid AA storage tank, resulting in the accidental leakage of gas
from a valve. Overnight, 12 cattle were found dead, with a total mortality of 64
cattle out of 260 on the premises dying or euthanized in < 1 week. Signs of
affected cattle included blindness, drooling, inappetence, respiratory distress,
recumbency, and death. Two cattle were submitted live for diagnostic evaluation 3
days after initial exposure. Gross lesions included corneal ulcers,
fibrinonecrotizing rhinitis, hemorrhages within the nasal sinuses, and
anterioventral bronchopneumonia. Microscopic lesions consisted predominantly of
degeneration and necrosis of superficial epithelium lining nasal passages,
trachea, and pulmonary airways. This case illustrates the acute AA effects on
cattle, which is likely to be an increasingly encountered problem because of on
farm storage of AA and its access by illicit drug manufacturers.
PMID- 17037622
TI - Vitamin A deficiency in turkey poults.
AB - Vitamin A deficiency was diagnosed in a commercial flock of 13,000 4-6-week-old
turkey poults in the summer of 2004. The birds were initially submitted for
examination because of a 3% increase in the reported daily mortality of the
flock. Clinically, affected birds had stunted growth and ruffled feathers, showed
signs of incoordination, and were depressed. At necropsy, pale white
pseudomembranous to mucoid material was observed on the mucosal surface of the
tongue, oral cavity, portions of the esophagus, and the crop of some birds.
Histologically, there was squamous metaplasia of the mucosal epithelium of the
oral mucosa, esophagus, sinuses, nasal glands, bronchi, proventriculus, and the
bursa of Fabricius. Vitamin A was not detected in the feed sample at a detection
limit of 0.5 mg/kg. Serum vitamin A concentrations in 7 birds were very low and
ranged from 0.05 to 0.1 mg/L. Vitamin A concentrations in livers were extremely
low (0.1 mg/kg wet weight, 1/7 poults) or undetectable (< 0.1 mg/kg wet weight,
6/7 poults). A diagnosis of vitamin A deficiency was made based on gross and
microscopic lesions and vitamin A concentrations in serum, liver, and feed. To
the authors' knowledge, this is the first documented case of vitamin A deficiency
in poults submitted from a commercial meat turkey producer comparatively
depicting the gross and microscopic lesions with those found in other species of
birds and mammals.
PMID- 17037623
TI - Monensin toxicosis in water buffaloes (Bubalus bubalis).
AB - The consumption of monensin-containing feed resulted in deaths of water buffaloes
from a feedlot in which cattle and buffaloes were kept together. The monensin
formulation was recommended only for use in cattle. Anorexia, muscular weakness,
dyspnea, and recumbency were the major clinical findings. The most significant
gross lesions were focal pale areas in semitendinosus and semimembranosus
muscles, in which segmental necrosis of myofibers was seen microscopically. To
compare susceptibilities of species to monensin, 3 bovine calves and 3 buffalo
calves were orally dosed. At 5, 7.5, and 10 mg/kg of monensin, only the buffaloes
became ill and died. Clinical signs initiated 18-20 h postdosing and were
comparable to those from field cases. Gross changes consisted of ascites,
hydrothorax, hydropericardium, hepatomegaly, and focal pale areas in the
myocardium and to a lesser degree in semitendinosus and semimembranosus muscles.
Histopathological changes also resembled those from the field cases, but were
especially pronounced in the myocardial cells. The hypothesis that buffaloes
could have a lower tolerance to monensin than cattle has been supported by
experimental cases.
PMID- 17037624
TI - Renal tubular necrosis and interstitial hemorrhage ("turkey-egg kidney") in a
circovirus-infected Yorkshire cross pig.
AB - A juvenile Yorkshire cross pig with rapidly progressive acute renal failure was
submitted for necropsy. There was marked edema and disseminated petechiation of
both kidneys, producing the "turkey-egg" appearance that is characteristic of
exotic diseases such as African and classical swine fever. Microscopic findings
included renal tubular epithelial necrosis with extensive interstitial edema and
hemorrhage; lymphoplasmacytic, eosinophilic, and histiocytic tubulointerstitial
nephritis; and numerous botryoid intracytoplasmic inclusions within the renal
tubular epithelium and interstitial macrophages. Porcine circovirus 2 (PCV2) was
readily identified within these lesions by both PCV2-specific
immunohistochemistical staining and electron microscopy. Tests for African and
classical swine fever viruses, as well as bacterial cultures, were negative. The
striking renal lesions in this pig were attributed to PCV2 infection and are
distinct from those that are typical of other PCV2-associated diseases.
PMID- 17037625
TI - Malignant nonteratoid ocular medulloepithelioma in a llama (Llama glama).
AB - A 6-year-old female llama presented with buphthalmos of its right eye owing to
the presence of an intraocular mass. The affected globe was enucleated and
submitted for microscopic examination. The intraocular mass was diagnosed as
malignant medulloepithelioma. Within the following months, the llama developed
soft tissue masses, which completely filled the right orbital cavity and expanded
the cranial portion of the right mandibular bone, and enlarged mandibular lymph
nodes. Euthanasia was elected 30 months after the initial diagnosis. The carcass
was submitted for postmortem examination, which revealed the presence of
medulloepithelioma metastases within the right orbit, mandible, mandibular lymph
nodes, lungs, liver, and mesenteric and sublumbar lymph nodes. The primary
intraocular tumor and its metastases were composed of neoplastic undifferentiated
neuroepithelial cells, which formed tubules, Flexner-Wintersteiner and Homer
Wright rosettes, and rare solid sheets. Electron microscopy showed that tumor
cells were connected by desmosome-like junctions and contained rare
intracytoplasmic basal bodies. Neoplastic cells were positive for vimentin,
nestin, microtubule-associated protein 1B, S-100 protein, and glial fibrillary
acidic protein (GFAP). To the best of the authors' knowledge, this is the first
report of a malignant nonteratoid ocular medulloepithelioma with distant
metastases in a llama and of the ultrastructural and extended immunohistochemical
characterization of a nonteratoid medulloepithelioma in this species.
PMID- 17037626
TI - Mixed thymoma in a cow.
AB - A neoplastic mass measuring 25 x 8 x 3 cm was found in the mediastinum of a 10
year-old Holstein cow. The neoplasm was encapsulated, multilobulated, and cystic.
Several firm adhesions were present between the neoplasm and the right cranial
lung lobe and the ipsilateral side of the pericardial sac. Under microscopic
examination, the neoplasm was characterized by solid sheets of spindle epithelial
cells (pancytokeratin and high molecular weight cytokeratin positive) subdivided
by fibrous trabeculae. Numerous individualized or small aggregates of mature T
cell (CD3 positive) lymphocytes were scattered throughout the neoplastic cell
population. Based on the gross, histologic, and immunohistochemical findings, the
neoplasm was diagnosed as a mixed thymoma.
PMID- 17037627
TI - Equine histoplasmosis presenting as a tumor in the abdominal cavity.
AB - A 3.5-year-old Thoroughbred mare presented at necropsy with a large mass at the
root of the mesentery and multiple smaller mesenteric masses. The mucosa of the
small intestine contained numerous raised nodules. Histologic examination
revealed severe granulomatous mesenteric lymphadenitis and enteritis. Epithelioid
macrophages and multinucleated giant cells frequently contained numerous
intracytoplasmic yeast organisms, which were strongly positive on
immunohistochemical staining when using a polyclonal antibody against Histoplasma
spp. A diagnosis of abdominal histoplasmosis was made based on the gross,
microscopic, and immunohistochemical findings.
PMID- 17037628
TI - Hepatic yersiniosis in a cougar (Felis concolor).
AB - A cougar (Felis concolor) was diagnosed with hepatic yersiniosis by bacterial
culture and histopathology. The animal had a 2-week history of anorexia and
jaundice before its death. Grossly, the liver exhibited caseo-necrotic foci.
Histopathologically, there was necrotizing and suppurative hepatitis, with large
numbers of intralesional gram-negative coccobacilli. Additional hepatic lesions
included central vein thrombosis, lymphoplasmacytic portal hepatitis, and
capsulitis. Yersinia pseudotuberculosis coccobacilli were isolated in pure
culture from the hepatic lesions. Because the hepatic lesions in this animal
resemble those of other zoonotic diseases, such as plague and tularemia,
veterinarians and laboratory personnel who handle samples should take adequate
safety precautions. This report is the first to describe the pathology associated
with hepatic yersiniosis in a cougar.
PMID- 17037629
TI - Lymphoma and Mycobacterium avium infection in a ferret (Mustela putorius furo).
AB - A 6-year-old, neutered male ferret presented with weight loss. Radiography
revealed an enlarged liver and other abdominal masses. The ferret was euthanized,
and at necropsy, the stomach wall was thickened, mesenteric lymph nodes were
enlarged, and the liver contained multifocal tan nodules. Histopathology
confirmed lymphoma and granulomatous inflammation in all affected organs. Acid
fast bacilli were present in the lesions and were confirmed to be Mycobacterium
avium by PCR.
PMID- 17037630
TI - DTC drug ads in the spotlight.
PMID- 17037631
TI - Personal best. Reaching your potential.
PMID- 17037632
TI - Economic credentialing: when hospitals play hard ball.
PMID- 17037633
TI - What my patients taught me about healing.
PMID- 17037634
TI - Breaking up is hard to do.
PMID- 17037635
TI - Stop losing money! Code better.
PMID- 17037636
TI - Can I pay a patient's bills?
PMID- 17037637
TI - Hand-held dynamometry: adoption 1900-2005.
AB - The purpose of this brief report is to describe the adoption of hand-held
dynamometry, a procedure for documenting muscle strength. Between the early 1900s
and the end of 2005, 478 research articles were published that documented use of
hand-held dynamometry. The adoption of the procedure for research is consistent
with the S-shaped curve described by Rogers. The extent to which hand-held
dynamometry is used in clinical practice remains to be delineated.
PMID- 17037638
TI - Reaction time reduction after parafoveal preview in a lexical decision task.
AB - Time and the accuracy of a lexical decision performed on a letter string (either
a word or nonword), presented foveally after a parafoveal preview displayed at 5
degrees of eccentricity and 100 msec. duration were measured. Students of Padova
University, 10 women and 7 men, ages 19 to 23 years were subjects. The hypothesis
investigated was whether the facilitatory effect, a reduction in lexical decision
time due to the parafoveal preview, was tied to global visual information
acquired in the visual periphery during the preview presentation. In Exp. 1,
eight subjects performed the task either with no preview (No Preview) or with a
preview presented at 5 degrees eccentricity in two conditions, preview of the
same foveal string (Preview-Letters) and preview of symbols ("x xx...") of the
same length as the foveal string (Preview Symbols). In Exp. 2, 9 subjects
performed the task with two preview conditions, No Preview and preview of the
foveal string in uppercase letters at 5 degrees of eccentricity (Preview
Uppercase). Analyses suggested the reduction in lexical decision time due to the
Preview with respect to the No Preview condition is tied to global information
extracted during parafoveal presentation. The reduction in lexical decision time
depends on word texture, i.e., letters' identities and also word boundary, in
addition to word length.
PMID- 17037640
TI - Pain perception as a function of self-focused rumination.
AB - Pain sensitivity and tolerance were studied using the cold-pressor technique. A 3
independent groups design was employed using rumination as the independent
variable. Group 1 was given a situation in which anger-related self-rumination
was introduced. Group 2 was given a self-related rumination task in which anger
was not induced. Group 3 received a rumination task not related to the self. In
addition, the State-Trait Anger Expression Inventory was given prior to the
experiment to test the hypothesis that ratings on the Anger-In subtest would
correlate with pain sensitivity. In each group were 6 men and 6 women. Each
participant took the anger and another inventory not relevant to the present
study before the experiment. An anger measure was taken before and after the
experiment for each group to see if the anger induction in Group 1 actually
increased anger. There were no differences among the 3 groups on the second anger
measure, so differences between Groups 1 and 2 could not be attributed to anger.
A 1-way analysis of variance for 3 groups showed a strong main effect on pain
tolerance but not pain sensitivity. Groups 1 and 2 were significantly more
tolerant of pain than Group 3. The correlation of ratings on the Anger-In
(internalized anger) subtest fell short of statistical significance with pain
sensitivity and also was not significant for pain tolerance. Results were
discussed in terms of the possibility that self-rumination may increase pain
tolerance by requiring a greater cognitive load than nonself rumination.
PMID- 17037639
TI - Grip strength and physical demand of previous occupation in a well-functioning
cohort of Chinese older adults.
AB - The grip strength of 214 independently ambulatory Chinese older adults (M age =
75.1 +/- 7.0 yr.) was measured, and preliminary mean values presented. Their
previous occupations were recorded, and the physical demands of those occupations
in terms of oxygen consumption and work done were classified. Grip strength
generally decreased across age groups. The physical demand of individuals'
previous occupations had significant associations with grip strength, for
example, participants who previously worked as construction site workers had a
greater grip strength than those who worked previously as office workers.
PMID- 17037641
TI - Sex differences and properties of the decreasing force during sustained static
grip at various target forces.
AB - The purpose of this study was to examine properties and sex differences of the
decreasing force during sustained isometric grip using various target forces,
50%, 75%, and 100% of maximal voluntary contraction (MVC), for 6 min.
Participants were healthy, 15 men (height = 172.9 +/- 4.6 cm, body mass = 67.7 +/
5.36 kg) and 15 women (height = 160.9 +/- 5.4 cm, body mass = 55.9 +/- 5.36 kg).
The force decrease for target forces of 75% and 100% MVC was marked until 60 sec.
from the onset of grip and then decreased gradually. On the other hand, the
target force of 50% MVC was maintained for about 60 sec. and then decreased
markedly until 100 sec. Differences in the decreasing force among target force
levels was observed until 60 sec., and there were no significant differences of
the time to decay to 20%, 30%, and 40% MVC. Namely, the time and force exertion
reaching an almost steady state were considered to be almost the same at any
target force. A sex difference on a parameter was found after 60 sec. or a
decreasing force after 40% MVC, and women held it longer or higher than the men.
However, the tendency was smaller in the latter phase of the steady state.
PMID- 17037642
TI - Multidimensional voice program analysis in profoundly deaf children: quantifying
frequency and amplitude control.
AB - Characterization of the vocal profile of profoundly deaf children using an
objective voice analysis was carried out in a university-based pediatric
otolaryngology clinic. 21 persons ages 3.5 to 18 years were assessed. From each
sustained phonation of the vowel /a/ the following acoustic variables were
extracted: fundamental frequency (F0), jitter percentage, shimmer percentage,
fundamental frequency variation (vF0), peak amplitude variation (vAM), and first,
second, and third formant frequencies (F1, F2, F3). Mean F0 was 267.8 Hz and
consistent with established normative data. Mean measurements of jitter (0.88%)
and shimmer (3.5%) were also within normal limits. The notable feature of the
acoustic analysis was a statistically significant elevation in vF0 (2.81%) and
vAM (23.58%). With the exception of one subject, the F1, F2, and F3 formant
frequencies were comparable to those for normal hearing children. Auditory
deprivation results in poor long-term control of frequency and amplitude during
sustained phonation. The inability to maintain a sustained phonation may
represent the partial collapse of an internal model of voice and speech.
PMID- 17037643
TI - Factors associated with perceived exertion and estimated time limit at lactate
threshold.
AB - The purpose was to identify the most predictive parameters for perceived exertion
and estimated time limit responses at the velocity corresponding to the lactate
concentration threshold. The former scale concerns the subject's current status
(how hard he feels the exercise currently is) whereas the latter scale deals with
a subjective prediction of how long the current exercise level can be maintained.
Multiple regression equations were developed among physiological, psychological,
nutritional, and individual parameters (subjects' characteristics and
performances) as independent variables, and perceived exertion or estimated time
limit as dependent variables. Independent variables were collected before or
during an incremental running field test. 94 regional to national level athletes
(47 endurance-trained runners, 11 sprinters, and 36 handball players)
participated. Multiple stepwise regression showed that Rating of Perceived
Exertion and Estimated Time Limit at the lactate threshold were mainly mediated
by factors relative to the performance expressed in percentage of the maximal
aerobic velocity. Secondary factors which contribute significantly as perceptual
predictors were related to various classes of factors except for psychological
factors.
PMID- 17037644
TI - Is time limit at the minimum swimming velocity of VO2 max influenced by stroking
parameters?
AB - The aim of this study was to observe the relationship between time limit at the
minimum velocity that elicits maximal oxygen consumption (TLim-v VO2 max) and
stroke rate, stroke length, and stroke index. 13 men and 10 women, highly trained
swimmers, performed an intermittent incremental test for v VO2 max assessment and
an all-out swim to estimate TLim-v VO2 max. The mean +/- SD TLim-v VO2 max, v VO2
max, stroke rate, stroke length, and stroke index values were 233.36 +/- 53.92
sec., 1.40 +/- .06 meter/sec., 35.58 +/- 2.89 cycles/min., 2.39 +/- .22
meter/cycle, and 3.36 +/- .41 meter2/(cycle x sec.), respectively. The
correlation between TLim-v VO2 max and stroke rate was -.51 (p < .01), and values
for TLim-v VO2 max with stroke length (r = .52, p < .01) and stroke index (r =
.45, p < .05). These results seem to suggest that technical skill is a key factor
in typical efforts requiring prolonged aerobic power.
PMID- 17037645
TI - Dissociative alterations in body image among individuals reporting out-of-body
experiences: a conceptual replication.
AB - A conceptual replication of the link between self-reported dissociative
alterations in body-image under experimental conditions and the reporting of
prior out-of-body experiences in a recent data set was undertaken. Also examined
was whether this relationship would hold for experiences reported during the
experimental context and whether it is independent of self-reported New Age
belief. Data from mostly undergraduates (N= 40; M age = 33.5, SD = 12.5; 27
women) in a mirror-gazing study were retrospectively analyzed. The 9 individuals
who reported prior out-of-body experiences, relative to those 31 who did not,
exhibited significantly greater self-reported dissociative alterations in body
image during the mirror-gazing task, even when the influence of scores on New Age
belief was controlled for statistically. The same differential relationship was
not found between 6 individuals who did and 34 who did not report out-of-body
experiences during the task.
PMID- 17037646
TI - Biomechanics Concept Inventory.
AB - A third version of a biomechanics concept inventory was developed and
administered to 41 kinesiology majors before and after an introductory
biomechanics class to build a larger pool of questions for course evaluation. The
test measured understanding of four prerequisite and eight competencies based on
national standards. Mean and standard deviation normalized gain was 29% (21) of
maximum possible improvement and was similar to previous versions of the test
given to students at the same university. Biomechanics instructors can use
questions from all versions of the Biomechanics Concept Inventory to customize
tests for evaluating instructional techniques in biomechanics.
PMID- 17037647
TI - Enabling a man with multiple disabilities and limited motor behavior to perform a
functional task with help of microswitch technology.
AB - This study evaluated the extent to which two microswitches used as interfaces
would enable a man with multiple disabilities and limited motor behavior to
operate an electric door opener at the entrance of the day center that he
attended. Analysis showed the man (a) learned to use the two microswitches, (b)
preferred the microswitch placed at his wheelchair's footrest (which also allowed
more effective responding) over the microswitch placed at his wheelchair's
armrest, and (c) maintained his positive performance at the 1- and 2-mo.
postintervention checks. The results were discussed from a technical and
practical standpoint and in terms of implications for the quality of life of
persons with disabilities.
PMID- 17037649
TI - Intensity and direction dimensions of competitive state anxiety: a time-to-event
approach.
AB - The purpose of the present study was to examine the temporally patterned changes
in intensity and direction of competitive state anxiety prior to and during
competition as well as correlations among intensity and direction on the
Competitive State Anxiety Inventory-2D subscale scores. 99 athletes completed the
inventory one day before and an hour before the competition, based on how they
felt during that time, and 30 min. after the competition with reference to how
they felt during the competition. Analysis indicated different temporal
patterning in subscale scores prior to competition. Correlations were medium
(.40) for Intensity and Direction dimensions. Significant differences were noted
between scores of those classified as Facilitators and Debilitators on the
Intensity dimension. The results support the multidimensional nature of
competitive anxiety. Moreover, additional information lies in directional
interpretation of competitive anxiety and self-confidence.
PMID- 17037648
TI - Sex and eyedness in a sample of Turkish high school students.
AB - The relationship of sex with eyedness was examined in 176 boys and 129 girls ages
15 to 21 years (M = 16.9 yr., SD = 1.8) in Turkish high schools. Sex was
significantly associated with handedness; the rate of left-handedness was 10.8%
in boys and 2.3% in girls and was not related to eyedness. Rate of left-eyedness
in the sample was 7.9% for boys and 8.5% for girls. One may wonder whether
eyedness shows a reverse sex effect, less than handedness, but methods of
measurement must be compared.
PMID- 17037650
TI - Form of athletic exercise, school environment, and sex in development of high
school students' sportsmanship.
AB - To examine the influence of form of athletic exercise, school environment, and
sex in the sportsmanship of high school students, 158 boys and 197 girls, ages 15
to 18 years (M = 16.0, SD = .7) in physical education at school, recreational
sports, and competitive sports at three schools were examined. Analysis of
students' responses on the Multidimensional Sportspersonship Orientation Scale
indicated the form of athletic exercise, the school environment, and sex were
related to their sportsmanship. These factors should be considered in planning
programs on moral education.
PMID- 17037651
TI - Reliability and factor structure of the Finnish version of the Sport Imagery
Questionnaire.
AB - The aim of this study was to examine the reliability and factor structure of the
Finnish version of the Sport Imagery Questionnaire, a measure which examines
cognitive and motivational functions of imagery. The final sample comprised 231
participants drawn from 34 sports and ranging in age from 14 to 49 years (M =
20.9, SD = 5.8). Internal consistency and confirmatory factor analyses were
undertaken to evaluate the reliability and factorial validity of the scale. Fit
indices and modification data generated from examining the 30-item five-factor
model were equivocal, suggesting minor amendment and recategorization of several
items rather than major adjustment to the proposed latent factor structure.
Cronbach coefficients alpha indicated the scale is reliable. Overall, these
results provide positive additional support for the claim that the Sport Imagery
Questionnaire has a reproducible factor structure and is a reliable test for
measuring imagery use in Finnish athletes.
PMID- 17037652
TI - Attitudes toward and approaches to learning first-year university mathematics.
AB - This study examined the relationship for 180 undergraduate students enrolled in a
first-year university calculus course between attitudes toward mathematics and
approaches to learning mathematics using the Mathematics Attitude Scale and the
Approaches to Learning Mathematics Questionnaire, respectively. Regression
analyses indicated that scores for the Mathematics Attitude Scale were negatively
related to scores for the Surface Approach and accounted for 10.4% of the
variance and scores for the Mathematics Attitude Scale were positively related to
scores for the Deep Approach to learning mathematics and accounted for 31.7% of
the variance.
PMID- 17037653
TI - Digit Symbol Substitution test performance: sex differences in a Hebrew-readers'
health population.
AB - The Digit Symbol Substitution test is simple to administer and sensitive to
individual differences related to cognitive performance. The present study
evaluated sex-related differences in performance by a Hebrew reading sample. The
test was administered to 275 men and 252 women (age range: 20-44 years). Hebrew
women significantly scored higher than the men. Means which increased during four
consecutive 30-sec. time periods of performance, was significantly greater for
the women than the men. This finding indicates women were more effective on this
pair-associated learning task than men.
PMID- 17037654
TI - Contact sports, moral functioning and planned behaviour theory.
AB - The goal was to test the psychometric properties of the Moral Functioning Scale
in a Greek athletic context, and to investigate any possible relation between
moral functioning and planned behaviour. The sample comprised 384 athletes, 103
from the sport of football (soccer), 97 from basketball, and 184 from water polo.
To measure moral functioning the researchers used a scale developed by Gibbons,
Ebbeck, and Weiss. Planned Behaviour was assessed with a questionnaire based on
Planned Behaviour Theory. Hierarchical regression analysis indicated strong
association for Attitudes, Intention, Role Identity, and Perceived Behavioural
Control with the four dilemmas of the moral functioning scale. The moral
reasoning measure is a promising tool for measuring athletes' moral dilemmas in
Greece.
PMID- 17037655
TI - Development of eating behavior by Japanese toddlers in a nursery school: relation
to independent walking.
AB - The eating behavior of 32 toddlers in a nursery school at 10, 12, and 14 months
old was observed in relation to the age at onset of independent walking. With
increasing age, the frequency at which the toddlers ate food given by a teacher
decreased, and the frequency at which the toddlers ate by themselves increased.
The toddlers who started walking earlier also advanced faster in the development
of eating behavior. The time when the frequency of eating by oneself surpassed
the frequency of passive eating coincided with the time when the toddlers started
walking.
PMID- 17037656
TI - Soccer players' muscular imbalances: restoration with an isokinetic strength
training program.
AB - The aim of the study was to investigate the effect of a muscular training program
on soccer players' performance which initially appeared imbalanced or bilaterally
asymmetrical. During the preparation period, 35 soccer players performed an
isokinetic measurement of knee flexors and extensors (60 degrees(-1) and 180
degrees sec.(-1)). 15 of these had muscular imbalances or deficits and followed a
specific isokinetic training program for 2 mo., 3 times per week. After the
completion of the isokinetic training program, the 35 players underwent the same
isokinetic test. Significant differences were noted between the pre- and
posttraining measures at both angular velocities in peak torque values, in
differences from one limb to the other, and in peak torque ratios for flexors and
extensors. Consequently, the application of this specific isokinetic training
program can restore imbalances in knee muscle strength efficiently.
PMID- 17037657
TI - Effect of static visual acuity on dynamic visual acuity: a pilot study.
AB - The aim of this pilot study was to evaluate whether dynamic visual acuity changes
with or without refractive correction. 42 healthy enrolled subjects with normal
vision were divided into two age-matched groups. In Group A, dynamic visual
acuity was measured first with the refractive error fully corrected and then
without. In Group B, dynamic visual acuity measurements were taken in the reverse
order of that performed by Group A. The measurements were binocularly performed
five times using free-head viewing after dynamic visual acuity values were
stable. Significant changes in dynamic visual acuity (static visual acuity 20/20
vs 12/20) were observed in both Group A (171.6 +/- 36.0 deg./sec. vs 151.8 +/-
39.6 deg./sec., Wilcoxon test, p < .001) and Group B (169.8 +/- 30.0 deg./sec. vs
151.2 +/- 36.0 deg./sec., Wilcoxon test, p < .001). The interaction was
significant (F1.20 = 8.12, p = .009). These results indicated that refractive
correction affected dynamic visual acuity.
PMID- 17037658
TI - Interactive decision-making: effects of consultation before personal decisions on
postdecision consolidation.
AB - Pre- and postdecision processes were studied in triads of participants, dyads of
participants, and for individual decision-makers in two experiment (N = 57 and
50). Participants were students volunteering to take part in the study (21 men
and 36 women with a mean age of 24 yr. and 25 men and 25 women with a mean age of
27 yr.). The purpose was to examine how much interactive versus individual social
interaction (consultation with others before making a personal decision) affects
postdecision consolidation. Predecision differentiation and postdecision
consolidation have been defined as attractiveness changes over time in favour of
the chosen alternative. Participants were coded into three categories
(noncompensatory, compensatory, and nonclassified) according to their different
decision strategies. For Exp. 1, postdecision consolidation effects were
significant for participants who used a noncompensatory (no comparisons across
attributes) decision strategy. For Exp. 2, postdecision consolidation effects
were significant for participants who made a personal decision but not those who
made an interactive decision. The differing results in these two experiments were
discussed.
PMID- 17037659
TI - Relation of age and passive properties of an ankle dorsiflexion stretch to the
timed one-leg stance test in older women.
AB - 26 older women (aged 65 to 89 years) participated in this study, which examined
the relationship of age and passive properties of a dorsiflexion stretch of the
calf muscle-tendon unit with one-leg stance times. Age was negatively correlated
with the time stance (r = -.75). The maximal passive dorsiflexion angle, length
extensibility, maximal passive dorsiflexion torque, and the area under the
passive curve (total passive elastic energy) were all positively correlated with
the stance time (range: r = .49-.69). A multiple regression analysis indicated
age was the best predictor of the times. Age and the maximal passive dorsiflexion
angle together accounting for 71% of the variance in the time (R = .84, R(2) =
.71). The addition of the remaining passive measurements did not improve the
variance accounted for in the one-leg stance time. The results indicated that the
maximal ankle dorsiflexion range of motion may be important for one-leg standing
balance of older women. Accordingly, stretching exercises designed to increase
the maximal dorsiflexion angle may have a role for maintaining or improving their
standing balance.
PMID- 17037660
TI - Effect of an auditory training program on reading, phoneme awareness, and
language.
AB - This investigation examined the effect of an auditory training program, Fast
ForWord-Language, with 26 children ages 7 to 10 years. As two subgroups based on
reading ability, all children received 6 wk. of intervention. Thresholds for
three conditions of backward masking were obtained pre- and postintervention, and
6 mo. afterward. Immediately following the intervention period, backward masking
thresholds improved for all backward masking conditions. Participants also showed
increases in language skills and in phoneme awareness but not in reading skills.
Six months after intervention, there were improvements in thresholds for backward
masking but no improvements in language or reading skills for either group. This
study calls into question the efficacy of an intensive auditory training program
to improve reading skills.
PMID- 17037661
TI - Young adult drivers' sensitivity to changes in speed and driving mode in a simple
vehicle simulator.
AB - The study was done to check replication of changes in sensitivity with a simple
simulator as had been obtained in an experiment using the real road situation.
Another purpose was to control simulator sickness which could have confounded
data from testing with a simulator or in actual driving. Sensitivity of the
drivers (72 healthy young adults, M age = 24 yr., SD = 5) while performing the
driving task was measured in terms of subjective ratings of simulator sickness
and affect, and physiological measures (i.e., galvanic skin responses and skin
temperature) at different driving speeds and in driving mode conditions, using a
simple vehicle simulator. Analysis showed measures of drivers' state, including
simulator sickness, physiological indices, and subjective reports, increased with
driving speed (30 --> 90 -->120 km/hr.) and driving mode change from the regular
speed to sudden increasing to sudden decreasing speeds. Particularly, the results
suggest that the increased autonomic nervous activation induces increase of rated
simulator sickness. Based upon the same tendency in change of the simulator
sickness and physiological state with driving speed and driving mode conditions,
it was concluded that, if the results obtained from the simulator experiment can
be generalized to the real situation, the simulator sickness must be considered a
confounding factor. The results also suggest that the changes in human
sensitivity are dependent upon aspects related to speed of a vehicle and driving
mode.
PMID- 17037662
TI - Smiling faces rated more feminine than serious faces in Japan.
AB - It has been reported that women and girls smile more frequently and more
effectively than men and boys. It is expected that this correlation between
femaleness and smiling affects the processing of faces, and consequently, smiling
faces may be perceived to be more feminine. Participants viewed 30 photographs
featuring smiling and serious facial expressions of both male and female subjects
and rated them for femininity or masculinity. The result indicated that smiling
faces significantly more frequently gave the impression of being more feminine.
The interaction between the sex of the faces and their expression was not
significant.
PMID- 17037663
TI - Reference values for the five-repetition sit-to-stand test: a descriptive meta
analysis of data from elders.
AB - This meta-analysis was conducted to generate normative values for the 5
repetition sit-to-stand (STS) test suitable for application to individuals at
least 60 years of age. A thorough review of the literature yielded 13 papers (14
studies) relevant to this purpose. After the exclusion of potentially
unrepresentative data, meta-analysis of these 13 papers indicated that judgments
about normal performance should be based on age. Analysis demonstrated that
individuals with times for 5 repetitions of this test exceeding the following can
be considered to have worse than average performance: 11.4 sec (60 to 69 years),
12.6 sec. (70 to 79 years), and 14.8 sec. (80 to 89 years).
PMID- 17037664
TI - Writing program with word prediction for a young man with multiple disabilities:
a preliminary assessment.
AB - This study assessed a writing program with word prediction, which completed the
writing of a word and spoke it out only when there was certainty that such a word
was the correct one. The assessment was carried out with a young man with
multiple disabilities, who typically used a word-processing program without word
prediction. The two programs were compared on the time required by the
participant for writing general sentences, through a social validation
assessment, and eventually a check on the participant's preference. Analysis
showed the program with word prediction was significantly more effective in terms
of the writing time, which was halved, and was deemed preferable by 40 raters
(psychology students) involved in the social validation assessment and by the
participant himself. Implications of the findings are discussed.
PMID- 17037665
TI - Assessments of young soccer players: a holistic approach.
AB - Use of scores on a single test of endurance which discriminates potentially
talented under-age players' performance is insufficient for prediction of later
performance, but such data could be useful when considered with other test
scores.
PMID- 17037666
TI - Comparison of isokinetic peak force and power in adults with partial and total
blindness.
AB - For many populations the ability to move efficiently is compromised by an
impaired muscular functioning. Strength development is necessary to overcome the
effects of gravity to maintain posture and generate movement responses for
mobility. The strength and power capabilities of individuals with total blindness
(n = 12) were compared to those with partial vision (n = 12) to evaluate effects
of vision on performance. Results indicate that (1) no significant differences
were apparent between total blindness and partial vision, (2) significant sex
differences were evident in each group, and (3) better performance was apparent
at lower velocities. It was concluded that physical performance in individuals
with blindness and partial vision are equally deficient.
PMID- 17037667
TI - Relations of perceived bodily changes with actual changes and changes in mood in
obese women initiating an exercise and weight-loss program.
AB - Significant relationships were found between mean difference scores for body
satisfaction and mood (rs = /.42 to .54/) for obese women (N = 50) beginning
exercise programs for weight loss. No significant relationships were found
between self-reported body satisfaction and measures of bodily changes. After
replication, implications for theory and treatment were discussed.
PMID- 17037668
TI - Contextual interference effect on acquisition and retention of pistol-shooting
skills.
AB - The effects of contextual interference on learning pistol-shooting skills in a
natural training environment were examined. The shooting skills consisted of
three "stages" with different requirements for the skill variations commonly used
in the field. 12 participants were randomly assigned into one of two practice
conditions, blocked vs serial. Following a 20-min. safety and skill instructional
session, Blocked group practiced 10 trials in a row at each stage, while Serial
group performed 5 trials in a row for each of the three stages and then repeated
the cycle. Both groups completed a total of 30 practice trials over the three
stages. A 10-min. rest interval was provided prior to a retention test which
included 9 trials (3 trials at each stage in a blocked format). Results based on
the data of Stage III, the most complex skill among the three stages, showed a
pattern consistent with previous findings that practicing in the serial schedule
depressed performance during initial training but maintained the performance
better at retention, relative to the blocked practice.
PMID- 17037669
TI - Perceived body size affected by garment and body mass index.
AB - This study investigated the effect of garment size on perceived body size. The
perceived body sizes of nine Chinese men, with Body Mass Index between 17.0 and
37.1 kg/m(2), wearing five sizes of white T-shirts were assessed using Thompson
and Gray's Nine-figural Scale. Garment sizes on perceived body sizes were
different for those of different Body Mass Index. A backpropagation neural net
model was used to model the nonlinear relationship between the perceived body
size and the body's BMI, body chest girth, and garment ease (difference between
garment and body chest girth). When the BMI was less than 20, wearing larger
sized T-shirts tended to increase perceived body size. For large chest sizes and
for taller persons (BMI of 20 to 28) large garments made the wearer look thinner.
However, for small persons (BMI of 20 to 28) effect of garment size was
relatively small. Obese persons (BMI of > 28), wearing garments too tight or too
loose were perceived as larger. Minimum perceived body size was found for garment
ease of 2 to 3 cm.
PMID- 17037670
TI - Tapping speed asymmetry in drummers for single-hand tapping with a stick.
AB - The purpose of this study was to investigate tapping speed asymmetry in 13 right
handed drummers and 13 right-handed nondrummers. The participants executed single
hand tapping with a stick as fast as possible for 10 sec. with the left and right
hand. There was no significant difference in the tapping speed of the right hand
between the drummers and the nondrummers, whereas in the left hand, the drummers
tapped significantly faster than the nondrummers. Drummers showed less tapping
speed asymmetry than nondrummers. These results suggest that the tapping speed of
the nonpreferred hand progressed nearly to the level of the preferred hand
through daily drum training.
PMID- 17037671
TI - Goal setting in acquisition of a volleyball skill late in motor learning.
AB - To examine the effects of different types of goal setting on motor skill
acquisition during advanced stages of learning. 44 female volleyball players were
tested in four experimental training groups with generic goals, specific long
term goals, specific short-term goals, and as a control group. This study's
pretest, training, and retention test phases used performance of a volleyball
dig/forearm pass oriented to a target. Analyses yielded no significant
differences among groups, although performance increased from pre- to retention
test.
PMID- 17037672
TI - Asymmetric recognition of pictures of cats as a function of age in 4-, 5-, and 6
year-old children.
AB - In the present study it was investigated whether children recognized deletions
more accurately than additions in pictures of animate objects as a function of
age between 4 and 6 years. Children, presented pictures of cats with features
added to or deleted from the original pictures, judged whether the pictures were
the same or different as those in a test of recognition. Analysis showed both 5
yr.-olds and 6-yr.olds discovered deletions more accurately than additions. This
asymmetric effect is in accord with that of adults, with whom the same stimuli
were used in earlier research, but are contrary to previous studies in which
additions were recognized more accurately than deletions when inanimate objects
were stimuli. Asymmetric effects, that is, greater recognition accuracy for
deletions may be related to children's being uncomfortable about modified
pictures of animals.
PMID- 17037673
TI - Music and physical activity in psychological well-being.
AB - The present study was designed to examine the effects of listening to music
during exercise of moderate intensity on mood, state anxiety, and time to
exhaustion as well as to evaluate sex differences in 27 physically active (14
men, 13 women) subjects between the ages of 20 and 30 years. Participants
completed the Profile of Mood States and the State Anxiety Inventory before and
after treadmill running in Music and No music conditions. Music and No Music
conditions were randomly assigned, and participants exercised at 75% of their
Heart Rate Reserve until voluntary exhaustion. Analysis indicated participants
reported statistically significant mean changes on Tension, Depression, Fatigue,
Confusion, and State Anxiety. However, the findings for emotions yielded no
significant effect of music, except findings suggested that women, but not men,
reported greater mean Fatigue after exercising in the presence of music than in
its absence. Also, there was a statistically significant finding suggesting that
women exercised longer with music than without.
PMID- 17037674
TI - Attitudes toward physical education classes of primary school students in Turkey.
AB - The purposes of this study were to report an investigation of attitudes toward
physical education in a sample of primary school students and examine the
predictive influence of students' sex, grades in physical education classes, and
parents' education and socioeconomic status on students' attitudes. Participants,
963 (474 girls and 489 boys) primary school students from Grades 6 (12.7%), 7
(10.3%) and 8 (77%), completed the Wear Attitude Inventory. Analysis indicated
students had positive scores on General Attitudes rather than on Social,
Emotional, and Physical Attitudes. In addition, girls (M = 32.6, SD = 3.9) had
more positive General Attitudes than boys (M = 32.0, SD = 4.6). Also, students'
grades in physical education classes were statistically significantly related to
their Attitudes toward physical education (Wilks lambda, F1,1110 = 2.88, p <
.05). However, parents' education and socioeconomic status were not. One may
infer that ways of encouraging more favorable attitudes might be planned.
PMID- 17037675
TI - Effects of religion and type of religious internalization on the mental health of
Iranian adolescents.
AB - This study was designed to assess the effects of religion and two types of
religious internalization on the mental health of Iranian adolescents. High
school students (82 Moslem and 37 Christian) were selected randomly from four
high schools in Shiraz and completed the Religious Self-regulation Questionnaire
and the General Health Questionnaire. Analysis showed that main effects of types
of religious internalization measured on four subscales of the General Health
Questionnaire were significant. Religion was significantly associated only with
somatic symptoms. For other scales no main effects of religion, types of
religious internalization, or their interactions were significant.
PMID- 17037677
TI - [Minimally invasive surgery of the pituitary and the sellar region].
AB - INTRODUCTION: New minimal invasive neurosurgical approaches for the treatment of
diseases in the sellar and perisellar regions (superciliary and paraseptal
approach, perioperative ACTH measurements, application of endoscopes and
neuronavigation) were introduced by the author. The modified surgical techniques
were applied by the author successfully in the treatment of more than 1000 cases,
of which the data of 746 patients were analysed and the results are presented.
METHODS AND RESULTS: The results of the clinical studies concerning superciliary
and paraseptal approaches were as follows: length of the operations and, loss of
blood were decreased, the patients needed shorter anesthesia and the treatment
cost became lower. The approaches were performed without hair cutting with
excellent cosmetic results leading to easier resocialisation of the patients. In
the group of the patients operated on through the superciliary approach
postoperative vasospasm developed in significantly lower rate, the number of days
spent in the intensive care unit decreased and the rate of patients on discharge
in good clinical condition were higher. The study on perioperative plasma ACTH
simultaneous measurements with rapid and standard methods revealed first in the
literature that, during anaesthesia in patients with ACTH producing adenoma the
plasma ACTH level changed individually. There was no difference between arterial
and venous plasma ACTH concentration in the same patient and the ACTH
concentration in the bleedings from the peripituitary bony structures are
individually variable, representing the network of the venous outflow of the
pituitary. The decrease in the plasma ACTH concentrations in the peripheral
venous samples two hours after operation and next morning proved the radical
removal of the adenoma. The differences between concentrations in the left and
right sides indicate the intrapituitary lateralization of the adenoma. The study
on the usefulness of neuroendoscopy and neuronavigation in the author's hand
revealed the advantages and disadvantages of these new neurosurgical instruments.
CONCLUSIONS: With the advent of the minimal invasive methods in surgery of the
pituitary and the sellar region the mortality end the morbidity of the operations
decreased.
PMID- 17037676
TI - [Expression of ZEBRA protein of Epstein-Barr virus in Hungarian patients with
Hodgkin lymphoma: latent or lytic cycle?].
AB - INTRODUCTION: Epstein-Barr virus is a ubiquitous human herpes virus in the
Hungarian population. The virus is associated with an increasing number of
lymphoid malignancies, such as Hodgkin and non-Hodgkin lymphomas. The ability of
the virus to establish life-long persistent infection and induce growth
transformation is related to the viral proteins that are variously expressed in
both normal and malignant cells. Although the presence of ZEBRA protein induces
lytic cycle, some lymphoma cases show this protein expression. AIM: In our
present study we investigated the frequency of expression of ZEBRA protein in
Hungarian patients with Hodgkin lymphoma associated with Epstein-Barr virus
infection. The authors wanted to clarify whether this expression is specific to
latency type II or occurs in some non-Hodgkin lymphoma cases with latency type
III as well. Does the expression of ZEBRA protein have any effect on therapeutic
response and survival rate of the patients? METHOD: 109 HL and 59 NHL were
studied for the presence of the virus in the tumor and for expression of the
latency proteins and ZEBRA by immunohistochemistry. RESULTS: 25 samples were
evaluated successfully for ZEBRA of the 47 LMP1 positive HL samples. We detected
the weak expression of ZEBRA protein in 13 of the 25 LMP1 positive Hodgkin
lymphoma cases and in 6 of the 18 LMP1 positive non-Hodgkin lymphoma samples. The
authors could not find correlation between the expression of ZEBRA protein and
the type of latency. During the followed 120 months the total survival of
patients with ZEBRA positivity proved to be significantly shorter as compared to
that of ZEBRA negative cases. The authors could not find significant difference
in the uneventful survival of these two groups. CONCLUSION: In the examined group
of patients the ZEBRA positivity associated with a poor prognosis of the disease.
Besides this relatively small number of cases, additional extensive studies are
needed to conclude our observation. Elucidation of the switching mechanisms by
which Epstein-Barr virus induces lytic cycle may provide an efficacious
therapeutic approach to the EBV-related malignancies.
PMID- 17037678
TI - [Obstructive sleep apnea and cardiovascular disease].
AB - Sleep-related breathing disorders are prevalent in the general population and are
associated with a wide range of cardiovascular diseases. Obstructive sleep apnea
is the most common form of sleep-related breathing disorders and is characterized
by repetitive episodes of partial or complete upper airway obstruction, followed
by oxygen-desaturation and arousals. These apneic events disrupt normal sleep and
lead to various acute and chronic cardiovascular consequences. The current
standard treatment with nasal continuous positive airway pressure eliminates
apneas, improves sleep fragmentation and prevents consequent hemodynamic changes
during sleep. Every patient with hypertension, obesity or heart disease should be
asked routinely about symptoms of sleep apnea and referred for a sleep study if
necessary.
PMID- 17037679
TI - [Fetal ischaemic brain injury in the second trimester of pregnancy].
AB - Based on clinical, epidemiologic, and experimental studies, the aetiology of
white matter damage, specially periventricular leukomalacia (PVL), is
multifactorial and involves pre- and perinatal factors. Each of these factors is
supposed to be a major precursor for neurological and intellectual impairment,
and cerebral palsy (CP) in later life. Antenatal rather than intrapartum factors
are now emerging as the major determinants of cerebral palsy. In this case report
maternal trauma, benign tumour, severe anaemia and fetal cerebral vascular
malformation are supposed as causative factors in intrauterine periventricular
leukomalacia resulting from hypoxic-ischaemic injury.
PMID- 17037680
TI - [Alopecia areata caused by extreme solar abuse].
AB - The Authors present a female patient who suffered from alopecia areata caused by
extreme solar abuse. Biological effects of ionizing radiation, the damages by
free radicals and protection against oxidative damage are summarized. The main
forms and risk factors of UV-radiation, skin damages by UV-light as well as the
pathogenesis of the alopecia areata are reviewed.
PMID- 17037681
TI - [Prostate cancer].
PMID- 17037682
TI - Fundamentals of research ethics--international and regional perspectives: welcome
address.
PMID- 17037683
TI - "To eat an elephant".
PMID- 17037684
TI - Research ethics: challenges in the Eastern Mediterranean Region.
AB - The foundations of ethical principles in the Eastern Mediterranean Region can be
found within the 3 major religions of the Region; Judaism, Christianity and
Islam. Today, there are numerous ethical issues that have emerged as result of
the technological advances of the 20th century and this paper addresses some of
those related to biomedical research. The Islamic principles in relation to
medicine and biomedical research are described, and in particular research
involving human subjects. The paper also outlines the endeavours being made by
the Islamic Organization for Medical Sciences to address such issues and draw up
recommendations and rulings.
PMID- 17037685
TI - Bioethics: a search for moral diversity.
AB - The concept of global, Asian and Chinese bioethics are discussed in this paper
and the difficulty in applying universal bioethics within different cultures and
countries is addressed. The traditional beliefs and values in China are described
with particular reference to medicine, and the implications for bioethics and
research ethics within the country are considered.
PMID- 17037686
TI - Research and developing countries: hopes and hypes.
AB - The paper outlines the universal problem of ensuring ethical practices in human
subject research, and focuses on specific difficulties faced in the developing
world with particular reference to Pakistan. It discusses the influence of
traditional and hierarchical social norms of physician-patient relationships in
heightening these problems. Two emerging issues of specific concern in Pakistan
are described: an exponential rise in multinational clinical drug trials, and
commercial ventures offering unproven stem cell "therapy" for all kinds of
diseases. The importance of introducing ethical practices in research within the
context of local cultural and socioeconomic realities is highlighted.
PMID- 17037687
TI - What is owed to the community before, during and following research: an ethical
dialogue.
AB - The paper briefly outlines some of the ethical issues involved in community-based
research particularly in developing countries. It focuses on informed consent,
confidentially and the obligations to the community or its members who
participate in the study. Most ethical guidelines are focused on the individual
participants. Yet increasingly the community may be the unit of study. More
attention will need to be directed towards developing guidelines for community
based research.
PMID- 17037688
TI - Pharmaceutical research: paradox, challenge or dilemma?
AB - A great deal of pharmaceutical research is nowadays carried out in developing
countries such as Pakistan. Is it, however, beneficial for the country and the
participants, often the poorly educated and illiterate? Pharmaceutical research
in Pakistan can bring benefits to both patients and country. Promotion of good
clinical practice and the development of national guidelines are advocated.
Government and industry both have a role to play to maintain the right balance.
PMID- 17037689
TI - Informed consent: views from Karachi.
AB - Little is known about the public's perceptions about the process of obtaining
informed consent for participation in medical research. A study was made of the
views of patients, their attendants, parents, schoolteachers and office workers
living in Karachi, Pakistan. Participants felt that informed consent was an
important step in recruiting research participants but many felt that it was a
trust-based process not requiring proper documentation. For recruiting women,
both men and women believed it was important to approach women through their
husbands and fathers. When there was a conflict with the opinions of family
leaders, it was clear that the male participants' opinion was valued more than
that of the female participants by both men and women.
PMID- 17037690
TI - Bioethics activities in India.
AB - The Indian Council of Medical Research formulates, coordinates and promotes
biomedical research in India. In 1980, they formulated the first national ethical
guidelines. They offer a number of different training programmes, from 1 day to 6
months. The council is developing a core curriculum for teaching bioethics, which
would be applied uniformly in medical schools throughout the country. Drug
development and ethics is also important in India, particularly now that the
local pharmaceutical industry is expanding and so many drugs trials are
outsourced to the country. The council is also very active in encouraging the
development of ethics review committees.
PMID- 17037691
TI - Regional perspectives in research ethics: a report from Bangladesh.
AB - Health research in Bangladesh is increasing and hence there is a need to consider
the ethical issues with regard such research. This paper describes the measures
being taken in Bangladesh to address research ethics, such as the bioethics
educational programmes and the ethics review committees functioning within the
country. The role and work of the Central Ethics Review Committee and the
regulatory guidelines are outlined. The paper also discusses the situation
regarding research ethics within the South Asia region.
PMID- 17037692
TI - Bioethics in Sri Lanka.
AB - Bioethics took off slowly in Sri Lanka, but now there are ethics review
committees in many medical schools and national organizations. All medical
schools teach some medical ethics but there are not enough trained teachers.
There are no national guidelines on research ethics. The Forum for Research and
Development was formed with the aim of building a new ethical research culture.
The bioethics initiative includes: awareness-raising; education activities and
capacity building; advocacy; and the development of policy guidelines. We aim to
raise awareness in the scientific community and the general public on ethical,
legal and social principles guiding the responsible conduct of research.
PMID- 17037694
TI - Epidemiology of malaria and predictions of retransmission in Babylon Governorate,
Iraq.
AB - After the 1997-98 malaria epidemic in Babylon governorate, Iraq, malaria
transmission in this area was successfully interrupted. A parasitological survey
in 2002 identified no malaria cases but an entomological survey found both
Anopheles stephensi and A. pulcherrimus in high densities. The highest density
was recorded in September and the lowest in December and January. Despite the
high density of Anopheles, no parasite sporozoites or oocysts were found in
dissected mosquitoes. Nevertheless, malaria transmission could recur if A.
stephensi indoor resting density exceeds the critical threshold and imported
malaria cases are not monitored.
PMID- 17037693
TI - Prevalence of HCV/HIV co-infection among haemophilia patients in Baghdad.
AB - To estimate the seroprevalence of HCV infection among HIV-infected haemophiliacs
and to demonstrate the most prevalent HCV genotype, 47 HIV-infected haemophilia
patients were screened for anti-HCV antibodies. By performing polymerase chain
reaction and DNA enzyme immunoassay, HCV-RNA was detected with subsequent
genotyping. Seroprevalence of anti-HCV antibodies was 66.0%. Of 31 HCV/HIV co
infected patients, 21 (67.7%) had no history of blood transfusion. We detected 4
HCV genotypes: 1a, 1b, 4 and 4 mixed with 3a, HCV-1b being the most frequent.
Contaminated factor VIII (clotting factor) could be responsible for disease
acquisition.
PMID- 17037695
TI - Environmental mycobacteria in areas of high and low tuberculosis prevalence in
the Islamic Republic of Iran.
AB - This research compared the numbers and types of different Mycobacterium species
in soil samples taken from 2 areas of Golestan province, Islamic Republic of
Iran, 1 with a high prevalence of tuberculosis and 1 with a low prevalence. From
220 samples, 91 grew positive cultures (41.4%) and 161 different strains were
diagnosed. The most common species isolated were Mycobacterium fortuitum, M.
flavescens and M. chelonae. The frequencies of environmental Mycobacterium in the
low-prevalence area were much higher than in the high-prevalence area, perhaps
due to different environmental fac-
PMID- 17037696
TI - Antimicrobial effectiveness of furazolidone against metronidazole-resistant
strains of Helicobacter pylori.
AB - The occurrence of strains resistant to metronidazole is causing failure of the 4
drug regimen for eradication of Helicobacter pylori in the Islamic Republic of
Iran. This study compared the in vitro efficacy of furazolidone with
metronidazole, clarithromycin, amoxicillin and tetracycline in 70 H. pylori
isolates from dyspeptic patients. Of the isolates, 33% were resistant to
metronidazole but all were susceptible to furazolidone. Furazolidone could be
considered as an appropriate substitute for metronidazole for H. pylori
infections.
PMID- 17037697
TI - Evaluation of rK39 strip test for the diagnosis of visceral leishmaniasis in
infants.
AB - This study estimated the sensitivity and specificity of the rK39 strip test
compared with the immunofluorescent antibody test and microscopy of bone marrow
aspirate smears (the gold standard) in 47 children with suspected visceral
leishmaniasis. A control group of children with other diagnoses (tuberculosis,
toxoplasmosis, systemic lupus erythematosus, malaria or cutaneous leishmaniasis)
were also tested to check false positive results. The sensitivity and specificity
of the strip test were 82.4% and 100% and that of immunofluorescent antibody were
100% and 92.7%. The rK39 strip test is reliable where there is no access to
laboratory facilities.
PMID- 17037698
TI - Hajj-associated acute respiratory infection among hajjis from Riyadh.
AB - A prospective cohort study was conducted to estimate the incidence of acute
respiratory infections (ARI) among hajjis registered at primary health care
centres of Riyadh. Out of 1027 hajjis, 39.8% developed symptoms of ARI. The
incidence of ARI was not statistically significantly associated with age, sex,
educational status or smoking. The risk of illness was significantly higher among
diabetics, hajjis who stayed longer in the hajj area and who prayed at Namera
mosque. Use of a facemask by men, but not use of a facecover by women, was a
significant protective factor against ARI.
PMID- 17037699
TI - Evaluation of the 10th External Quality Assessment Scheme results in clinical
microbiology laboratories in Tehran and districts.
AB - We evaluated the performance of microbiology laboratories in the 10th run of the
external quality assessment scheme (EQAS) in Tehran and districts. Each
laboratory was sent 2 species of bacteria for identification. Of the 487
laboratories that participated, 437 returned their findings. While 77.0% and
69.9% correctly identified Staphylococcus saprophyticus and Citrobacter freundii
respectively, only 29.8% correctly identified Acinetobacter baumanii, 25.3%
identified Enterococcus faecalis and 35.6% identified Enterobacter agglomerans.
However 78.7% and 79.5% of the laboratories reported correct -results for
susceptibility testing for S. saprophyticus and C. freundii respectively.
PMID- 17037701
TI - Differential aspects of consultation-liaison psychiatry in a Saudi hospital. II:
knowledge and attitudes of physicians and patients.
AB - To assess the attitude and knowledge of physicians and patients towards
psychiatry, we asked 115 referring doctors and 188 referred patients to complete
questionnaires. We examined the results along with the referral rates to try to
identify factors that may affect a consultation-liaison psychiatry service.
Generally, knowledge was poor and attitudes towards psychiatry negative in both
groups. This negatively influenced the referral rates and reflected the lack of
integration of psychiatry and medicine at the training level. This is an
indication that psychiatrists need to work in collaboration with hospital doctors
to integrate psychiatry into medicine at all levels and emphasizes the priority
of education of hospital staff, patients and the community in consultation
liaison psychiatry.
PMID- 17037700
TI - Differential aspects of consultation-liaison psychiatry in a Saudi hospital. I:
referral pattern and clinical indices.
AB - Consultation-liaison psychiatry has emerged as an important sub-specialty in the
general hospital setting during recent years as a result of psychiatric acute
wards moving into these hospitals. This has inspired the need for better
structured research to establish its relevance and effectiveness. We, therefore,
carried out a prospective cohort study at King Fahad General Hospital. We report
the interaction of sociodemographic, clinical and diagnostic factors, time lag of
referral and diagnostic ability of referring physicians. A total of 206 patients
were referred over a period of 6 months. Sensitivity and specificity of the
diagnostic skills of the referring doctors were found to be generally poor,
particularly for anxiety.
PMID- 17037702
TI - Health Workers for Change: a tool for promoting behaviour change among health
providers.
AB - Sensitizing health providers to customers' needs and women's health remains a
challenge to the Pakistani health system. The Health Workers for Change
methodology has been demonstrated to improve provider-client relationships in
certain African and Latin American countries. This paper describes the experience
of using Health Workers for Change participatory workshops in Pakistan to
sensitize male and female health providers to gender issues. Health care
providers identified the unmet needs of women clients as a function of
individual, household and societal factors, and, unlike the African experience
with this tool, not predominantly confined to factors associated with the health
facility.
PMID- 17037703
TI - Problems related to shiftwork for health care workers at Shiraz University of
Medical Sciences.
AB - A cross-sectional study of shiftwork-related problems was carried out among
health care workers at hospitals of Shiraz University of Medical Sciences,
Islamic Republic of Iran. Data on personal details, shift schedule and adverse
effects of shiftwork were collected from 432 randomly selected subjects by
questionnaire. Sleep, social and subjective problems were more prevalent in
shiftworkers than day workers. Irregular shiftwork schedules caused more social
and subjective problems, as well as work dissatisfaction. Voluntary selection of
shiftworking produced fewer health problems.
PMID- 17037704
TI - [Current situation of health services in northern districts of the West Bank,
Palestine].
AB - We assessed the current situation of health services in the northern districts of
the West Bank of Palestine as regards the providers of the services, the services
provided, the human resources working in the services and the sufficiency of the
services with respect to the size of the populations. We found that 21% of the
total population in the northern districts did not have private medical clinics
and 13% did not even have primary health care centres. There has been an increase
in the number of governmental primary health care centers and a decrease in the
number of nongovernmental and charitable centres since the Palestinian National
Authority took over responsibility for public health services through the
Ministry of Health.
PMID- 17037705
TI - [Assessment of medical waste management in a Palestinian hospital].
AB - We studied medical waste management in a Palestinian hospital in the West Bank
and the role of municipality in this management. In general, "good management
practices" were inadequate; there was insufficient separation between hazardous
and non-hazardous wastes, an absence of necessary rules and regulations for the
collection of wastes from the hospital wards and the on-site transport to a
temporary storage location inside and outside the hospital and inadequate waste
treatment and disposal of hospital wastes along with municipal garbage. Moreover,
training of personnel was lacking and protective equipment and measures for staff
were not available. No special landfills for hazardous wastes were found within
the municipality.
PMID- 17037706
TI - Children's indoor and outdoor play patterns in Ahwaz City: implications for
injury prevention.
AB - A cross-sectional study in Ahwaz city, Islamic Republic of Iran, described
children's indoor and outdoor play patterns. A total of 952 pupils aged 7 and 9
years and 942 parents completed questionnaires. Children's favourite activities
were: playing football (22.3%), cycling (13.2%) and watching television (12.3%).
This differed from those perceived by the parents who reported watching
television (20.3%), playing football (13.3%) and playing in street (11.4%).
Children reported their favourite places to play were: street (27.4%),
park/playground (18.3%) and home (17.8%). There were significant differences in
play patterns by age and sex. The play patterns of older children and boys
exposed them to more hazardous situations than younger children and girls.
PMID- 17037707
TI - Epidemiology of deaths from injuries in the Islamic Republic of Iran.
AB - A 1-year study of fatal injuries was carried out in 10 provinces of the Islamic
Republic of Iran based on a population of 16 740 637 in 2000-01. All reported
deaths were compared and validated with other sources of death registration. Out
of 66 846 deaths, 9733 (58/100 000) resulted from injuries. Overall, 14.9% of all
deaths with 26.9% of years of lost life were from injuries. Most fatal injuries
were unintentional (48.0/100 000). Deaths from traffic injuries (30.0/100 000)
are the highest in the world. Of 1693 intentional fatal injuries, 61% were due to
suicide, at a mean age of 29 years.
PMID- 17037708
TI - Attitudes towards euthanasia among final-year Khartoum University medical
students.
AB - To investigate the attitudes of final-year medical students at Khartoum
University towards euthanasia an anonymous questionnaire was answered by 141
students. Most were familiar with the concept of euthanasia. The majority, 108
(76.6%) opposed euthanasia and their reasons included religious beliefs, belief
that euthanasia was unethical and fear of misuse. The supporters of euthanasia
(23.4%) stated reasons such as preventing the suffering of patients and
respecting their autonomy and dignity. More students who described themselves as
strongly religious were opponents of euthanasia (83/87, 95.4%) than those who
were moderately religious (25/54, 46.3%).
PMID- 17037709
TI - [Applying a teaching programme in community-based medical education].
AB - A community-based medical education programme at Damascus University was applied
in a local setting from 2 to 12 July 2004 to assess the advantages and
disadvantages. Three families and 10 medical students participated. The programme
included teaching objectives, health education and approaches to application and
evaluation. The design of the programme was appropriate for the community
setting, but it needed a longer period to run and for contact between the
students and the community. The students agreed with the structure of the
programme and the role of the tutor and community, but were concerned about
difficulties in implementation. Community members were enthusiastic about the
programme.
PMID- 17037710
TI - [Smoking among Lebanese mothers: knowledge, attitudes and practices].
AB - Smoking among women is increasing, especially in women of reproductive age. In a
cross-sectional study of 1000 Lebanese mothers, we evaluated their knowledge,
attitude and practice regarding cigarette smoking. We found that the amount of
tobacco smoked by Lebanese mothers was related to age, educational level,
profession and knowledge regarding smoking. A woman was more likely to stop or
decrease smoking during pregnancy if she were more knowledgeable about the
effects of smoking on the baby, if she smoked less, and if she had a higher
degree of education. Knowledge about the effects of smoking on the smoker did not
seem to affect this practice.
PMID- 17037711
TI - Use of combined oral contraceptives: retrospective study in Isfahan, Islamic
Republic of Iran.
AB - We carried out a retrospective cross-sectional study on 500 women in Isfahan who
started taking combined oral contraceptives (COCs) during the period 21 March
1995-20 March 1997. The cumulative continuation rate fell from 77% to 12% over 60
months. The most common reason for discontinuation was side-effects. There was a
significant correlation between side-effects and cumulative COC continuation rate
(P < 0.05). The lowest rate was seen in women reporting nausea or vomiting. Women
who are interested in COCs should receive extensive counselling about the
possible side-effects and should be helped to find a method of birth control
suited to their temperament and physiology.
PMID- 17037712
TI - Comparison of the effectiveness of fennel and mefenamic acid on pain intensity in
dysmenorrhoea.
AB - A study in Kerman, Islamic Republic of Iran in 2002 compared the effectiveness of
fennel and mefenamic acid on pain relief in primary dysmenorrhoea. Two groups of
high-school girls (mean age 13 years) suffering dysmenorrhoea were randomized to
receive fennel extract (n = 55) or mefenamic acid (n = 55) for 2 months. In the
fennel group, 80% of girls and in the mefenamic acid group, 73% of girls showed
complete pain relief or pain decrease, while 80% in the fennel group and 62% in
the mefenamic acid group no longer needed to rest. There was no significant
difference between the 2 groups in the level of pain relief.
PMID- 17037713
TI - Knowledge, attitudes and beliefs about menarche of adolescent girls in Anand
district, Gujarat.
AB - A questionnaire survey of knowledge, attitudes and beliefs towards menstruation
was made in 22 schools in Anand district, Gujarat state. Of 900 schoolgirls aged
11-17 years, only 38.5% felt comfortable about menarche and only 31.0% believed
that menstruation was a normal physiological process. Many (37.2%) had not been
informed about menarche before its onset and 48.2% felt they were not mentally
prepared. The major sources of information were the mother (60.7%) or an elder
sister (15.8%); teachers and others relatives played a small role. In this area
of India, many families continue the custom of celebrating the first menarche and
observing social restrictions.
PMID- 17037714
TI - Prevalence and risk indicators of myopia among schoolchildren in Amman, Jordan.
AB - We aimed to identify the prevalence and risk factors of myopia among secondary
school students in Amman. Thus 1777 (1081 males and 696 females) students aged 12
17 years old were recruited from 8 schools randomly selected from 8 different
geographic locations in Amman. Data were collected by questionnaire, and self
reported myopia was checked against school medical records. The prevalence of
myopia was 17.6%, with no significant difference between males and females after
adjusting for other possible variables. Myopia was significantly associated with
age, family history of myopia, computer use, and reading and writing outside
school. Playing sports was inversely associated with myopia but there was no
association with watching television.
PMID- 17037715
TI - Influence of Surgicel gauze on the incidence of dry socket after wisdom tooth
extraction.
AB - At a hospital in Damman, Saudi Arabia, it was noticed that many patients had
developed dry socket after surgical removal of wisdom teeth. To enhance
haemostasis, Surgicel (oxidized cellulose) gauze was sometimes used in the tooth
socket in patients who were operated under general anaesthesia. An analysis was
made of the records of 104 lower wisdom teeth removed surgically from 86
patients. The incidence of dry socket in the 20 Surgicel-treated teeth was 25.0%,
compared with 6.0% among the 84 non-Surgicel-treated teeth. The use of Surgicel
in wisdom tooth extraction seems to be associated with an increased incidence of
dry socket.
PMID- 17037716
TI - Wastewater reuse for agriculture: regional health perspective.
AB - The Eastern Mediterranean Region of the WHO is the poorest region in the world in
water resources as a Region and per capita. This paper summarizes existing
practices and constraints regarding wastewater treatment and reuse in the Region
and describes the health impact of inappropriate practices. Appropriate treatment
for agricultural use from the health point of view, and the health regulations
and guidelines for wastewater reuse in the Region are outlined. The work of the
WHO Regional Office to assist countries face the challenges of water scarcity and
wastewater reuse are described. Finally, key suggestions that could enhance the
use of reclaimed wastewater while at the same time safeguarding human health are
presented.
PMID- 17037717
TI - Rebuilding of the Lebanese health care system: health sector reforms.
AB - The civil war in Lebanon from 1975 to 1992 had a significant negative impact on
the public health care system. This paper describes the health care system in
Lebanon and its financing as of 2001. The efforts that have been made and are
being made to rehabilitate and reform this sector since the end of the war are
outlined.
PMID- 17037718
TI - Meriones libycus is the main reservoir of zoonotic cutaneous leishmaniasis in
south Islamic Republic of Iran.
AB - A study was made in rural regions around Neiriz city, Fars province in the south
of the Islamic Republic of Iran during 2002-03 to further investigate a new focus
of zoonotic cutaneous leishmaniasis. Meriones libycus was the dominant rodent
(100% of 65 rodents collected) and 4.6% were naturally infected with the
amastigote form of Leishmania spp. Promasigotes were identified as L. major. This
confirms M. libycus as the main reservoir host of zoonotic cutaneous
leishmaniasis in southern parts of the country.
PMID- 17037719
TI - Antiperspirant use as a risk factor for breast cancer in Iraq.
AB - Some internet communications have addressed the link between antiperspirant use
and breast cancer. We studied the possible association between the use of
antiperspirants and some other factors with the development of breast cancer in
Al-Kadhmia teaching hospital. Thus, 54 cases of breast cancer and 50 controls
were interviewed. We found 82.0% of the controls used antiperspirants compared
with 51.8% of cases (P< 0.05). The use of antiperspirants had no association with
the risk of breast cancer, while family history and oral contraceptives use were
found to be associated.
PMID- 17037720
TI - Inguinal hernias and genital abnormalities in young Jordanian males.
AB - This study was carried out to document the prevalence of inguinal hernia,
hypospadias, undescended testis and varicocele in 3057 male applicants to the
military wing of Mu'ta University in the south of Jordan. Age range was 17-20
years. A total of 250 men had one the 4 conditions: 93 (3.0%) had inguinal
hernia; 15 (0.5%) had undescended testis (26.7% bilateral); 59 (1.9%) had
hypospadias; 83 (2.7%) had varicocele (98.79% on the left side). Prevalence of
inguinal hernia and undescended testis were comparable with international
prevalence rates, while the rate for hypospadias was higher and that for
varicocele lower. A birth defects registration system would help in planning
preventive and treatment strategies.
PMID- 17037721
TI - Bilharzial infection of a uterine leiomyoma.
PMID- 17037722
TI - [The cloning and expression of rhlR, a quorum sensing gene in Pseudomonas
aeruginosa PAO1, and a study of its effect on bacterial clearance rate in mouse
lung].
AB - OBJECTIVE: To inquire about the molecular characteristics of rhlR, a Quorum
Sensing gene in Pseudomonas aeruginosa (P. aeruginosa) PAO1, and to explore the
immunogenicity of RhlR protein in mouse. METHODS: The rhlR gene of PAO1 was
amplified by PCR and cloned into pGEX4T-1 plasmid. The recombination was
expressed in E. coli BL21 (DE3) and analyzed by SDS-PAGE and Western blotting.
The fusion protein (GST-RhlR) was purified by GST purification Kit and the
purified protein was used to immunize mice. P. aeruginosa PA0315 was injected
into mouse lung to explore the immuno-protection of the protein. RESULTS: The 726
bp DNA fragment of rhlR was amplified from PAO1 general DNA. The restriction
enzyme map showed that the inserted part of rhlR-pGEX4T-1 was successfully
constructed and the gene was 100% homologous to rhlR in GenBank. The recombinant
plasmid expressed a 54 kDa fusion protein (rhlR-GST) in E. coli BL21 (DE3) after
induction by IPTG. The fusion protein could be recognized by mouse polyvalent
antiserum against P. aeruginosa. The results showed that the bacterial clearance
rate in mouse lung was 86. 92% in rhlR groups and 49.44% in the control group.
CONCLUSION: A 54 kDa protein (RhlR-GST) has been successfully expressed in E.
coli BL21 (DE3). The RhlR could increase the bacterial clearance rate in mouse
lung and may serve as immunoprotective antigen to develop the genetic engineering
vaccine.
PMID- 17037723
TI - [Quantification for biofilm formation of pseudomonas aeruginosa isolates and
their genotypic analysis].
AB - OBJECTIVE: To probe the correlation between the ability of biofilm formation of
Pseudomonas aeruginosa isolates and their genotypes. METHODS: Forty-eight
Pseudomonas aeruginosa isolates were tested for their biofilm formation with a
modified microtiter test and were analyzed by enterobacterial repetitive
intergenic consensus PCR (ERIC-PCR). The percent similarity between their genetic
fingerprints and cluster analysis was performed and worked out using computer
software. RESULTS: Forty-eight Pseudomonas aeruginosa isolates demonstrated
different abilities of biofilm formation in vitro. And the 48 isolates with
different abilities of biofilm formation showed different genotypes in
fingerprints by ERIC-PCR. Among the 48 isolates of Pseudomonas aeruginosa tested,
five clusters (A, B, C, D, E), were identified at the 17% genetic similarity
level. The isolates with strong ability of biofilm formation were in D cluster at
the 42% genetic similarity level. CONCLUSION: Most of the 48 PA isolates tested
formed strong biofilm, and their genotypes were of correlation.
PMID- 17037724
TI - [Construction and expression of prokaryotic expression vector pTWIN1/TRAIL].
AB - OBJECTIVE: To purify an active extracellular region of the TNF related apoptosis
inducing ligand (TRAIL) protein. METHODS: According to the high-usage codons in
Escherichia coli and the multiple cloning site of expression vector pTWIN1 of a
self-splicing prokaryotic expression system, the extracellular region of TRAIL
gene was designed and synthesized, which was cloned into pMD18-T vector. After
pMD18-T/TRAIL and pTWIN1 were digested by Nru I and EcoR I, the target fragment
purified was linked to the expression vector pTWIN1, which was transferred into
the competent cell JM109, and positive recombination was screened. After positive
recombination vector pTWIN1/TRAIL (identified with restrictive endonuclease
digesting and sequencing) was transferred into the ER2566, the expression was
induced by different IPTG concentration at different temperature and culture
time. The expression products were analyzed by 150 g/L SDS-PAGE. RESULTS: The
extracellular region of TRAIL gene was obtained by PCR, and was constructed
successfully in a self-splicing prokaryotic expression vector pTWIN1/TRAIL. By
0.3 mmol/L IPTG at 15 degrees C for 14 to 16 hours, the soluble target protein
was expressed efficiently. CONCLUSION: High-expression level of the extracellular
region of TRAIL fusion protein was attained by use of E. coli ER2566, and the
soluble target protein without any additional amino acid was successfully
purified by simple treatment.
PMID- 17037725
TI - [The cloned ctxA gene of vibrio cholerae expresses in E. coli].
AB - OBJECTIVE: To construct the expression vector of Vibrio cholerae ctxA gene, and
realize the Vibrio cholerae ctxA gene to express in E. coli, and lay a basis for
future research on the immunogenicity and immunoadjuvant. METHODS: The ctxA gene,
an cholera toxin subunit gene (ctxA) of Vibrio cholerae, was obtained by
polymerase chain reaction (PCR) from DNA of Vibrio cholerae, and cloned into
prokaryotic expressed vector pET32a(+) with thioredoxin (Trx) gene. The
recombinant plasmid (pET-ctxA) was analyzed to identify with restriction
endonuclease digestion, PCR and DNA sequencing analysis. And then the pET-ctxA
was transferred into E. coli strain BL21 (DE3) for transformation. The ctxA
expression of pET-ctxA was induced with isopropy-beta-D-thiogalactoside (IPTG)
and the fused protein Trx-CTA was examined by SDS-PAGE and Western blot
techniques. RESULTS: Restriction endonuclease digestion, PCR and DNA sequencing
analyses showed that the ctxA gene of 787 bp was amplified from Vibrio cholerae
DNA, and the recombinant plasmid pET-ctxA was successfully constructed, and the
ctxA expression in prokaryotic cell was detected by SDS-PAGE and Western blot
techniques. CONCLUSION: The ctxA gene of Vibrio cholerae, in fused protein form
with Trx, got a high expression in E. coli.
PMID- 17037726
TI - [The influence with block the endotoxin signal transduction for
ischemia/reperfusion injury of graft liver in rats].
AB - OBJECTIVE: To explore the feasibility of interleukin 1 receptor associated kinase
4 (IRAK-4) as gene therapy target for liver ischemia/reperfusion injury (I/RI)
and effective approach in vivo for short hairpin RNA (shRNA) interference used to
gene therapy in liver graft hqappened. METHODS: Sprague-Dawley rats were randomly
divided into three groups: the control group, the in vivo transfection group
(IVT) and the cold ischemia transfection group (CIT). Experiments of orthotopic
liver transplantation were performed by two-cuff method. CIT were perfused with
IRAK-4-shRNA plasmid (pSIIRAK-4) during cold ischemia phase, IVT received the
equivalent volumes (2 mL) of pSIIRAK-4 after portal vein inosculated, and the
control group leaved without any treatment. At 0 min, 60 min and 180 min after
reperfusion, the expression of IRAK-4 gene and protein level were determined by
RT-PCR and Western blot. The serum TNF-alpha level was detected by ELISA. Liver
histopathological changes and cell apoptosis were observed by electron microscope
and TUNEL. RESULTS: After reperfusion, the expression of IRAK-4 were largely
depressed in CIT than that of IVT and the control group (P < 0.01), and
furthermore, the serum TNF-alpha level, proportion of hepatocyte apoptosis and
severity of hepatocyte injury were also lower than the latter. CONCLUSION: These
results indicate that depression IRAK-4 expression with IRAK-4-shRNA through
portal vein perfusion during cold ischemia phase could effectively blunt graft
hepatic I/RI.
PMID- 17037727
TI - [Evidence for the presence of motilin receptor and a study on the mechanism of
motilin induced Ca2+ signaling in rat myenteric neurons].
AB - OBJECTIVE: To observe whether the motilin receptor (MTLR) can be expressed in
primarily cultured myenteric neurons of rats and investigate the mechanism of
motilin induced Ca2+ signaling in myenteric neurons of rats. METHODS: Expression
of the motilin receptor was identified with double-immunofluorescence staining
technique. Data on the intracellular Ca2+ concentration ([Ca2+]i) of cultured
myenteric neurons with different treatments were collected by measuring Ca2+
fluorescent intensity (FI) in each neuron under confocal microscope. RESULTS: The
cultured myenteric neurons showed positive motilin receptor immunoreactivity. In
Hank's solution, 10(-6) mol/L motilin could elevate [Ca2+]i, its height of peak
being 30.6 +/- 3.7 and its FI relative change percentage being (100. 8 +/-
18.4)%. In D-Hank's solution (after removal of extracellular Ca2+, or after
treatment with verapamil,an L-type calcium channel blocker), motilin could induce
a small increase of [Ca2+]i. After pretreatment with NEM,a G protein inhibitor,
and Compound 48/80, a PLC inhibitor, in Hank's solution respectively, motilin was
inhibited and the [Ca2+]i was significantly lower than that of the group to which
was added only motilin (P < 0.05). After pretreatment with D-sphingosine, a PKC
inhibitor, the effect of motilin was not significantly different from that of the
group to which was added only motilin (P > 0.05). CONCLUSION: The motilin
receptor could be expressed by cultured myenteric neurons of rats. Motilin could
increase [Ca+]i. The increase of [Ca2+]i was caused by release of intracellular
stores and influx of extracellular Ca2+, mainly through the L-type calcium
channel. The motilin receptor-coupled G-protein, PLC and IP3 pathway participated
in the release of Ca2+ from intracellular stores.
PMID- 17037728
TI - [Effect of batroxobin on K+ channel activated by Ca2+ in primary culture rat
cortex neurons of rat].
AB - OBJECTIVE: To investigate the effect of batroxobin on K+ channel activated by
Ca2+ in primary cultured cortex neurons of fetal SD rat. METHODS: The patch clamp
technique of single channel recordings including cell-attach and inside-out mode
was used. RESULTS: Extracellular batroxobin activated the Kca. In Ca2+ bath
solution of cell-attach mode, Vp +30 mV, when the concentrations of batroxobin
were 0.15, 0.25, 0.50, 0.75 and 1.0 mmol/L, the open probabilities of the channel
were 0.013 +/- 0.002, 0.082 +/- 0.011, 0.131+/- 0.012, 0.211+/- 0.010 and 0.062
+/- 0.009 (P < 0.01), respectively. It appeared concentration-dependent within
0.75 mmol/ L. batroxobin. In Ca2+ free-bath solution of cell-attach mode, Vp+50
mV, when the concentrations of batroxobin were 0.15, 0.40, 0.60 and 1.0 mmol/L,
the open probabilities of the channel were 0.013 +/- 0.001, 0.112 +/- 0.007,
0.193 +/- 0.010 and 0.301 +/- 0.009 (P < 0.05), respectively. In the 6 cases of
inside-out mode patch clamp, Vp +40 mV, when the concentrations of batroxobin
were 0, 0.25 and 0.50 mmol/L, the open probabilities of the channel were 0. 012
+/- 0.007, 0.011 +/- 0.009 and 0.013 +/- 0.008 (P > 0.05), respectively. There
was no significant difference in open probabilities, average open/close times and
amplitudes at different intracellular batroxobin concentrations. CONCLUSION:
Batroxobin can affect the activation of the Kca channel through regulating the
concentration of cytoplasmic free Ca2+. It may have a protective effect on
neurons.
PMID- 17037729
TI - [Changes of mitochondrial membrane potential (delta psi m) and calcium
concentration in cultured glomerular mesangial cells of rats with obstructive
jaundice].
AB - OBJECTIVE: To explore the effect of mitochondrial membrane potential (delta psi
m) and calcium concentration on the kidney injury of rats with obstructive
jaundice and to probe into the underlying mechanism. METHODS: Sixty male Sprague
Dowley rats, weighing 200 g to 250 g were randomly divided into three groups:
control group; sham operation group; experiment group. And the rats of experiment
group were subdivided into two groups according to the time (15 d, 21 d) after
the common bile duct ligation. The experiment groups were rendered jaundiced by
doubly ligating the common bile duct. Glomeruli were isolated, the glomerular
mesangial cells (GMCs) were cultured. The mitochondrial membrane potential (delta
psi m) was measured by flow cytometry; the concentration of calcium was measured
by confocal microscopes. RESULTS: The amount of mitochondrial membrane potential
(delta psi m) was decreased (P < 0.05) in the rats with obstructive jaundice,
compared with the control; the concentration of calcium was increased (P < 0.05)
in the rats with obstructive jaundice, compared with the control. Conclusion The
calcium incurrent that leads to changes in amount of mitochondrial membrane
potential (delta psi m) has significant effect on the kidney injury of the rats
with obstructive jaundice.
PMID- 17037730
TI - [Human amnion cells express the phenotypes of neural cells and adipocytes in
vitro].
AB - OBJECTIVE: To search for culture conditions in which the cells from human amnion
could diferentiate into neural cells and hence to explore a new cell source for
neural transplantaion. METHODS: Amnion cells from human were cultured with tissue
piece method, passaged by trypsin digestion and identified with
immunocytochemistry. RESULTS: Amnion cells migrated from explants and primary
culture was established; they could multiply and expand steadily in a short time,
and they could be passaged by trypsin digestion. When cultured in serum-free
neural stem cell media, these cells could form the same spheroid shape as the
neurospheres of neural stem cells. They could express alpha smooth muscle actin
and differentiate into smooth muscle cells spontaneously, and could express
nestin and vimentin, the markers for neural progenitors. Moreover, they could he
stained by anti-beta III-tubulin, anti-neurofilament 200 and anti-NSE; the
majorities could he stained by antityrosine hydroxylase, the marker for
dopaminergic neurons. Lower than 0.1% of the total cells were stained by GFAP,
indicating the existence of astrocytes. The amnion cells could also differentiate
into adipocytes under specific induction. CONCLUSION: Amnion cells could
differentiate into adipocytes and smooth muscle cells; they could express the
protein for neural cells; thus may represent an alternative stem cell source for
CNS cell transplantation.
PMID- 17037731
TI - [A study on transfection of green fluorescence protein gene into human adipose
stromal cells in vitro].
AB - OBJECTIVE: To make a comparison on the efficiency of two methods for transfecting
Green Fluorescence Protein gene into human adipose tissue-derived stromal cells,
and to study the biological properties and multipotential differentiation of gene
transfected cells. METHODS: The human subcutaneous adipose tissue was obtained,
digested with one volume of collagenase type I, and then cultured with BGJb
medium. After subculture and expansion, the human adipose tissue-derived stromal
cells infected with Ad-GFP or liposome were observed and analyzed with
fluorescence microscopy and flow cytometry to assess transfection efficiency. The
growth curve of transfected adipose tissue-derived stromal cells was protracted.
The adipose tissue-derived storomal cells were induced to differentiate into
osteoblasts, and non-transfected cells were set as control. RESULTS: 42.5% +/-
1.5 of the human adipose tissue-derived stomal cells infected with Ad-GFP were
found to express GFP at a level higher than that of the control of liposome
(11.40%). Infected adipose tissue-derived stromal cells were noted to form
mineralized nodes by the use of Alizarin Red stain. CONCLUSION: The human adipose
tissue-derived stromal cells infected with Ad-GFP can express higher level of
GFP, and can maintain the ability of proliferation and differentiation as the non
infected human adipose tissue-derived stromal cells do. The infected adipose
tissue-derived stromal cells with Ad-GFP can track the change of adipose tissue
derived stromal cells in the study of multipotential differentiation and can
serve as cellular vehicles for systemic gene delivery.
PMID- 17037732
TI - [Anti-tumor effects of recombinant adenovirus encoding survivin encapsulated in
cationic liposome].
AB - OBJECTIVE: To explore the anti-tumor effects and mechanisms of recombinant
adenovirus encoding survivin encapsulated in cationic liposome. METHODS: CT26
tumor model was established in BALB/c mice. Fifty mice were randomly divided into
five groups, including the group treated with recombinant adenovirus encoding
survivin encapsulated in cationic liposome (Lip+ Ad-sur), the group of
recombinant adenovirus encoding survivin (Ad-sur), the group of recombinant
adenovirus encoding null encapsulated in cationic liposome (Lip+Ad-null), the
group of liposome (Lip), and the group of PBS alone (PBS). Survival rate of mice,
tumor volume, and side effects of treatments were observed. Lymphocytes were
activated by adenovirus vaccine to kill tumor cells in vitro and in vivo. CTL
assay and histological examination were carried out. RESULTS: Immunotherapy with
recombinant adenovirus encoding survivin encapsulated in cationic liposome was
effective for inducing protective and therapeutic anti-tumor immunity in CT26
tumor model. In the combination therapy group, the tumor growth was inhibited and
the tumor volume was significantly smaller when compared with the controls. The
survival rate of mice in the combination therapy group at 7 weeks after
inoculation of tumor cells was significantly higher than that of the control
group. Histologically, the tumor tissue was markedly necrotic and was infiltrated
by lymphocytes. 51Cr assay in vitro indicated that the combination therapy group
showed higher specific killing activity against CT26 tumor cells than did the
control groups, and the T cells were independent of NK cells. CONCLUSION:
Immunotherapy with recombinant adenovirus encoding survivin encapsulated in
cationic liposome was noted to have a significant anti-tumor effect on CT26 tumor
model.
PMID- 17037733
TI - [An experimental research on the combination treatment of sFLK-1 gene therapy
combined with gamma knife].
AB - OBJECTIVE: To evaluate whether the sustained expression by adenovirus-mediated
gene (sFLK-1) transfer can enhance the treatment efficacy of gamma knife
radiosurgery. METHODS: The mouse sFLK-1 gene was cloned to construct the
recombinant adenovirus. The gliomata growing in BALB/c female nude mice with an
initial mean volume of (109.3 +/- 20.5) mm3 were treated with gamma knife alone
(13 Gy on day 12), sFLK-1 adenovirus alone (1 x 10(9) plaque-forming units, PFU
was given to two mouse tail vein by injections, 7 and 14 days), gamma knife
associated with sFLK-1 adenovirus or control adenovirus (1 x 10(9) PFU was given
to two mouse tail vein by injections, 13 and 17 days). After the completion of
therapy, the tumor size was recorded. The microvessel density (MVD) and tumor
apoptosis were evaluated by immunohistochemical means. RESULTS: As comparing with
three other control groups, the combination treatment group with sFLK-1 gene
therapy and gamma knife not only significantly reduced tumor volume and prolonged
the life span of tumor burden mice as well. In addition, the average tumor
weights were lower in sFLK-1 combined with gamma knife group than in any other
control group. Immunohistochemical analysis of glioma demonstrated a decreased
MVD and a high apoptosis cell rate in sFLK-1 combined with gamma knif group.
CONCLUSION: The antitumor effect of gamma knife can be potentiated by sFLK-1 gene
therapy. Thus the combination of sFLK-1 gene therapy and gamma knife results an
additive effect of antitumor. The observation may provide an important strategy
for treatment cancer metastasis.
PMID- 17037734
TI - [Effect of lenti-mCCL20 on the growth of mouse tumor].
AB - OBJECTS: We aim at inducing a potent antitumor immune response via CCL20
expressing in situ tumor. METHODS: We constructed a recombinant lentivirus
encoding mouse CCL20 cDNA and transduced the mouse mesenchymal stem cells (mMSCs)
in vitro, and then selected the transfected cells to get a stable mixed mCCL20
expressing pool (named as lenti-mCCL20-mMSCs) with blasticidin. By the same
means, we produced another pool named as lenti-null-mMSCs. The CT26 was mixed
with lenti-mCCL20-mMSC and inoculated sc into the left hinder back of BALB/c
mouse. And also the CT26 was alone, or mixed with lenti-null-mMSCs or parent
mMSCs, and then inoculated sc into BALB/c mice serving as controls. RESULTS: We
got a lenti-mCCL20-mMSCs expression construct. It was shown that mCCL20 increased
intratumoral lymphocytes infiltration and facilitated tumor growth in syngeneic
murine tumor model. CONCLUSIONS: CCL20 expressing in situ tumor enhances
intratumoral lymphocytes infiltration but facilitates tumor growth. However, the
mechanism involved remains to be further elucidated.
PMID- 17037735
TI - [Effects of soy isoflavone on gene expression of resistin in insulin-resistance
rats].
AB - OBJECTIVE: To assess the effects of soy isoflavone (SIF) on improving insulin
reistance (IR) status in IR rats induced by high-fat and high-sugar diet and
explore the possible mechanisms. METHODS: IR rats were randomly divided into four
groups according to their insulin resistance indices (IRI). The rats in one model
control group and three SIF groups were fed via gavage with water solutions
containing SIF at doses of 0 mg/ kg x bw, 50 mg/kg x bw, 150 mg/kg x bw, and 450
mg/kg x bw, respectively. After one month, fasting glucose, fasting insulin,
resistin in serum, and resistin mRNA in adipocyte around kidney were detected by
enzymologic method, radioimmunoassay, enzyme linked immunosorbent assay, and real
time RT-PCR, respectively. RESULTS: Comparison between the model control group
and the other groups revealed that serum resistin and resistin mRNA expression
levels were lower in the 450 mg/kg x bw group, that insulin and IRI levels were
lower in the 150 mg/ kg x bw group and 450 mg/kg x bw group, and that no
differences in plasma glucose levels existed among the 4 groups. A positive
correlation between IRI and serum resistin level (r = 0.355, P < 0.05) was
observed. CONCLUSION: These results suggest that soy isoflavone may down-regulate
resistin mRNA expression, decrease serum resistin level and enhance insulin
sensitivity.
PMID- 17037736
TI - [Effects of TGF-beta1, gene modified donor dendritic cells on immune repulsion].
AB - OBJECTIVE: To examine the inhibitory action of the injection of TGF-beta1 gene
modified donor dendritic cells (TGF-beta1-DC) on the immune repulsion in rat
liver transplantation and detect the related mechanism. METHODS: The recombinant
TGF-beta1-pcDNA3 adenovirus transfected Wistar DCs were injected into the tail
vein of the recipient SD rat. One week later, the rat immune repulsion model of
liver transplantation was set up, the expression of TGF-beta1 gene was
identified, and the survival was observed and recorded. The NF-kappaB activity
and cell factor TNF of T cells in recipient spleen and Kupffer cells were
detected by electrophoretic mobility shift assay and immunohistochemistry
respectively. The pathological rejection index after transplantation was assayed.
RESULTS: The rejection index was decreased and the survival time was prolonged in
Ad-TGF-beta1-DC group as compared with those in control groups. Also it was found
that TGF-beta1-DC injection inhibited the expression of NF-kappaB and TNF of T
cells and Kupffer cells in rat liver allografts, and all differences were
statistically significant. CONCLUSION: TGF-beta1 gene modified DC could obviously
inhibit the activation of T cells and Kupffer cells, enhance the tolerogenicity
of liver transplantation and prolong survival time.
PMID- 17037737
TI - [Effect of ligustrazine on cell proliferation in subventricular zone of lateral
cerebral ventricle after adult rat suffering from focal cerebral ischemia].
AB - OBJECTIVE: To explore the effect of ligustrazine on cell proliferation in
subventricular zone of lateral cerebral ventricle after middle cerebral artery
occluded (MACO) in adult rat. METHODS: SD male rats were randomly divided into
three group: sham operation group, ischemic model group and Ligustrazine group.
The model of the middle cerebral artery occlusion was established by placement of
an intraluminal filament at the origin of left MCA. Ligustrazine was administered
intraperitoneally with a dose of 80 mg/kg daily starting at 2 hours after MCAO.
BrdU (50 mg/kg) was injected once a day intraperitoneally starting at 4 hours
after operation. Number of BrdU-positive cells and expression of doublecortin
(DCX) in subventricular zone (SVZ) were measured by immunohistochemistry on day
7, 14, 24 after operation. RESULTS: Compared with sham operation group, BrdU
positive cells in ischemic model group increased on day 7, reached the peak on
day 14, then decreased on day 21 after operation. On day 7 and 14, the numbers of
BrdU-positive cells in Ligustrazine group were markedly augmented and
significantly more than those in ischemic model group (P < 0.01), but decreased
on day 21. The expressions of DCX in SVZ in ischemic model group were enhanced on
day 7 with lasting into day 14, and reduced on day 21, but still higher than
those in sham operation group on day 7, 14, and 21, respectively. The expressions
of DCX in SVZ in Ligustrazine group increased gradually along with prolong of
ischemia and kept the high level up to day 21 after operation, and were higher
than those in ischemic model group on day 14 and 21. CONCLUSION: Our results
suggest that Ligustrazine may promote the cells of SVZ, which the adult rats
suffer from the focal cerebral ischemia, to go into cell proliferation.
PMID- 17037738
TI - [A study on expression of HIF-1alpha and EPO in the hippocampus of rats with
vascular dementia].
AB - OBJECTIVE: To observe the expression rule of hypoxia inducible factor-1 (HIF
1alpha) and erythropoietion (EPO) in the formation of vascular dementia (VD) and
investigate the possible pathogenesis of VD. METHODS: Rats of experimental group
were treated with a permanent bilateral common carotid arteries (CCA) occlusion
(2-VO) for establishing vascular dementia model. Rats were evaluated on learning
memory ability by Y-type water maze test. The dynamic expression of HIF-1alpha
and EPO in hippocampal CA1 region were measured by immunohistochemical assay
method. RESULTS: (1) The learning-memory ability of rats in VD groups was
progressively decreased as the ischemic duration prolonged (P < 0.05); (2) In VD
group, the expression of HIF-1alpha and EPO in hippocampal CA1 region were most
obvious at 1 w, and then declined progressively but still above the normal level
(P < 0.01); (3) In VD group, the expression of HIF-1alpha and EPO at each
ischemic point and their corresponding learning-memory ability were in
significant correlation at the 0.01 level. CONCLUSION: Both HIF-1alpha and EPO
contribute to the formation of VD, and HIF-1/EPO anoxic signal transduction may
play a protecting role in this process.
PMID- 17037739
TI - [Inhibitory effects of deoxyribozyme on the expression of Period1 gene in vitro
and on morphine-induced psychic dependence in mice].
AB - OBJECTIVE: To investigate the regulatory effects of deoxyribozyme on the
expression of Period 1 gene in vitro and on the morphine-induced psychic
dependence in mice. METHODS: The specific deoxyribozymes toward Period 1 mRNA was
designed by MFold analysis and synethsized chemically. By LipofectAMINE mediated
DNA transfection technique, DRz164 and pcDNA3-Per1 were introduced into NIH3T3
cells. The effects of deoxyribozyme on Period 1 gene were studied by reverse
transcript-polymerase chain reaction (RT-PCR) and flow cytometry(FCM). The
morphine-induced reward in mice was observed in a conditioned place preference
test after pretreatment of the mice with the intracerebroventricular
administration of deoxyribozyme. RESULTS: After NIH3T3 cells were transfected by
pcDNA3-Per1 and DRz164, the Period 1 mRNA was reduced by 42.4%. And PERIOD
proteins were decreased by 57.5%. After being pretreated with deoxyribozyme, the
mice did not show morphine-induced place preference. CONCLUSION: DRz164 can
highly block the expression of Period 1 gene, which cleaves the Period 1 mRNA in
the transfected cells specifically. The suppression of morphine-induced place
preference can be effected by pretreating the mice with alleviating their psychic
dependence on morphine.
PMID- 17037740
TI - [Expression level of cubilin in the rat model of diabetic nephropathy].
AB - OBJECTIVE: To observe the expression level of Cubilin in the renal tubules of
rats with STZ-induced diabetic nephropathy, to assess its correlation with 24
hours' albuminuria, and to investigate the mechanisms of tubular dysfunction at
the early stage of diabetic nephropathy. METHODS: Diabetic nephropathy was
induced in Sprague-Dalwley rats by intraperitoneal injection of STZ, while the
rats of normal group were injected with normal saline. Biochemical indices of
blood and urine specimens were observed in both groups at weeks 2, 4 and 6
respectively. The renal expression levels of Cubilin in the two groups were
determined by immunohistochemistry and RT-PCR. RESULTS: The expression level of
Cubilin in the diabetic nephropathy group was significantly decreased at week 2
after operation (P < 0.05), and it continued to decrease from week 2 to week 6.
Also there was significant difference between each two time-points (P < 0.05),
and the Cubilin expression level was negatively correlated with albuminuria (P <
0.01). CONCLUSION: The decreased expression level of Cubilin in early-stage
diabetic nephropathy rats may partly contribute to the development of
microalbuminuria. Cubilin can be regarded as one of the early markers when
tubular dysfunction develops in the case of diabetic nephropathy.
PMID- 17037741
TI - [Differential regulation of P2X3 mRNA expression in the rat trigeminal ganglion
after experimental tooth movement].
AB - OBJECTIVE: To investigate the regulation of P2X3 mRNA expression in the
trigeminal ganglion sensory neurons after the nociceptive stimulation by
orthodontic tooth movement force. METHODS: Male Sprague-Dawley rats weighing 200
250 g were used. The mimic tooth movement appliance was used in the rats of the
experiment group. The rats were sacrificed after 4 h, 12 h, 1 d, 2 d, 3 d, 5 d
and 7 d after experiment. The expression of P2X3 mRNA was detected by in situ
hybridization with an oligonucleotide probe. RESULTS: After force was given to
the teeth of rats, the number of P2X3 mRNA positive neurons increased on the
first day and reached the peak on the third day; then, the level of P2X3 mRNA
expression began to decrease, and after seven days, it returned to the level of
the control group. CONCLUSION: The results suggest that the P2X3 mRNA expression
is transiently upregulated and anterogradely transported in trigeminal primary
sensory neurons after orthodontic tooth movement and that P2X3 receptor may play
a role in the pathomechanism of nociception in primary sensory neurons during
orthodontic treatment.
PMID- 17037742
TI - [Expression of PPAR-gamma in human hilar bile duct carcinoma cell line QBC939 and
the effects of PPAR-Y activated by its ligand on the growth of QBC939].
AB - OBJECTIVE: To explore the expression of Peroxisome Proliferator-activated
Receptor-gamma (PPAR-gamma) in QBC939 and the effects of PPAR-gamma activated by
its ligand pioglitazone on the growth of human bile duct carcinoma cell line.
METHODS: QBC939 cells were cultured and treated with different concentration of
pioglitazone; the expression of PPAR-gamma mRNA was detected by RT-PCR; the
effects of PPAR-gamma activated by its ligand on cell proliferation were examined
by cell count under light microscope; the influences of activated PPAR-gamma on
cell cycle were examined by flow cytometry, and the apoptosis of cancer cells
induced by PPAR-gamma ligand pioglitazone was detected by flow cytometry and
TUNEL methods. RESULTS: PPAR-gamma was expressed in human hilar bile duct
carcinoma cell line QBC939. And after PPAR-gamma was activated by its ligand
pioglitazone, it significantly inhibited cell proliferation, produced G2/M phase
arrest and induced apoptosis of QBC939. CONCLUSIONS: PPAR-gamma, after being
activated by its ligand pioglitazone, can inhibit the cell growth of QBC939
remarkably through suppression of cell proliferation, increase in proportion of
G2/M phase cells and induction of apoptosis, so PPAR-gamma may be a molecular
therapeutical target against the human bile duct carcinoma.
PMID- 17037743
TI - [Reflux of bile induces esophageal mucosal inflammation and apoptosis in rats].
AB - OBJECTIVE: To investigate the esophageal mucosal inflammation and apoptosis
induced by reflux of different duodenal or bile in rats. METHODS: Esophagus
division in esophagogastric junction and then esophagoduodenostomy were performed
on rats to make the models of duodenogastroesophageal reflux (DGER). Three kinds
of reflux model, DGER (Group A), duodenoesophageal reflux without gastric juice
(Group B) and DGER without bile (Group C) were made by adjusting the DGER models.
9 weeks after operation, the esophageal mucosal inflammation was examined under
microscope, and the esophageal apoptosis was tested by DNA fragmentation in situ
using TdT-mediated dUTP biotin nick end labling (TUNEL). Immunohistochemical
method was used to detect the status of esophageal Fas protein (CD95) associated
apoptosis. RESULTS: Evidences of reflux esophagitis were seen in all rats with
different reflux models. Esophageal inflammation was most severe in group A, then
in group B, and the slightest in group C. Barrett's esophagus was seen in group A
and group B but not in group C, and the incidence was found to be of no
difference between the A and B groups (P > 0.05). Esophageal mucosal apoptosis
index in group A was (7.05 +/- 1.44)%, being significantly higher than that in
group B (5.25 +/- 1.78)% and group C (2.84 +/- 1.36)%, (P < 0.01). The apoptosis
index was significantly higher in group B than in group C (P < 0.01). Fas protein
was negative in normal tissues and in all injured esophageal mucosal tissues.
CONCLUSION: The DGER without bile inflicts the slighest injury on the esophageal
mucosa. Bile may play a significant role in the induction of Barrett's esophagus.
The apoptosis indices increase in groups A, B and C, but apoptosis is not
correlated with Fas expression.
PMID- 17037744
TI - [Expression level and significance of TGF-beta1, PDGF, CTGF in serum of patients
with pneumoconiosis].
AB - OBJECTIVE: To explore the TGF-beta1, PDGF, CTGF serum expression significance in
the occurrence and development of pneumoconiosis. METHODS: The serum levels of
TGF-beta1, PDGF, CTGF in 70 patients with pneumoconiosis (including 29 patients
with silicosis and 41 patients with coal pneumoconiosis) and 77 healthy
individuals were detected by means of enzyme linked immunosorbent assay (ELISA).
RESULTS: The serum levels of TGF-beta1, PDGF, CTGF in patients with
pneumoconiosis were (44.95 +/- 23.72) ng/mL, (56.95 +/- 55.68) ng/mL, (346.70 +/-
259.49) pg/mL, the serum levels of control group were (6.81 +/- 4.99) ng/mL,
(30.96 +/- 21.63) ng/mL, (307.49 +/- 235.40) pg/mL. There were significantly
statistical differences between the case group and the control group in the serum
levels of TGF-beta1 and PDGF (P < 0.05). There was no significantly statistical
difference between the two groups in the serum levels of CTGF (P > 0.05). The
serum levels of TGF-beta1 and PDGF in the patients with silicosis were higher
than those in the patients with coal pneumoconiosis, and there was significantly
statistical difference between the two groups (P < 0.05). The serum levels of TGF
beta1 and PDGF in the patients with pneumoconiosis decreased with the
pneumoconiosis stage going up (P < 0.05). There was the bivariate correlation not
only between the serum levels of TGF-beta1 and PDGF in the whole objects but also
the serum levels of CTGF and PDGF (P < 0.05). CONCLUSIONS: The serum levels of
TGF-beta1, PDGF, CTGF in the patients with pneumoconiosis may correlate with the
pathological stages, styles and degree of pneumoconiosis.
PMID- 17037745
TI - [Effects of nonsteroidal anti-inflammatory drug celecoxib on expression of
cyclooxygenase-2 (COX-2) in ovarian carcinoma cell].
AB - OBJECTIVE: To explore the effects of nonsteroidal anti-inflammatory drug
Celecoxib on the expression of cyclooxygenase-2 (COX-2) in the SKOV3 cell line
and the xenografted nude mice of ovarian carcinoma. METHODS: The expression of
COX-2 in the SKOV3 cell was determined by reverse transcription polymerase chain
reaction (RT-PCR), flow cytometry (FCM), and Western blot analysis. The
expression of COX-2 in tumor cells was measured with Immunocytochemistry.
RESULTS: RT-PCR showed that the expression COX-2 mRNA was strongly down-regulated
in SKOV3 cells after treatment with Celecoxib or Aspirin. FCM and Western blot
analysis showed that the protein product of COX-2 was strongly decreased by
Celecoxib or Aspirin. The Celecoxib was more potential effects than Aspirin. The
immunocytochemistry result showed that the expression of COX-2 in 10, 25, 50
mg/kg x d of Celecoxib were lower obviously than it in the control group in
Xenografted nude mice. CONCLUSION: The anticarcinogenic effects of Celecoxib is
probably related to the down-regulation of COX-2, and can be explained to both
COX-2-dependent and -independent mechanisms.
PMID- 17037747
TI - [The relativity of vascular endothelium growth factor receptor-1 and
preeclampsia].
AB - OBJECTIVES: (1) To investigate the levels of the serum soluble endothelial growth
factor receptor-1 in women with preeclampsia and compare the difference between
the groups of the mild preeclampsia, severe preeclampsia and eclampsia. For more,
to analyze the relativity between the levels of the serum soluble vascular growth
factor receptor-1 and preeclampsia. (2) To detect the expression of the membrane
bound VEGFR-1 protein in the placenta tissue of the women with preeclampsia and
compare the difference between the groups of the mild preeclampsia, severe
preeclampsia and eclampsia, Then to analyze the relativity between the expression
of the membrane-bound endothelial growth factor receptor-1 and preeclampsia.
METHODS: (1) The serum levels of sVEGFR-1 in 10 women with mild preeclampsia, 10
women with severe preeclampsia, 10 women with eclampsia, 10 women without
preeclampsia were detected by the quantitative sandwich enzyme immunoassay
technique. (2) Immunohistochemistry and quantitative analysis were used to detect
membrane-bound VEGFR-1 contents and distribution in the placenta tissue. RESULTS:
(1) The results showed that the serum sVEGFR-1 levels of all preeclampsia groups
were relatively higher than those of control group (P < 0.05) and that there were
significant differences between the groups of the mild preeclampsia, severe
preeclampsia and eclampsia. (2) In placentas, the positive staining was detected
predominantly in the membranes of villus syncytiotrophoblast cells, extravillous
trophoblast cells, and villus endothelial cells. In fetal membranes, the positive
staining was detected predominantly in amnionic endothelial cells. (3) The
contents of membrane-bound VEGFR-1 in placenta of preeclampsia groups were
relatively lower than that of control group. There were significant differences
between membrane-bound VEGFR-1 contents of the mild preeclampsia,severe
preeclampsia and eclampsia (P < 0.05). (4) The ratio of the sVEGFR-1
concentration in serum and the membrane-bound VEGFR-1 contents in placenta of
preeclampsia groups (sVEGFR-1/ membrane-bound VEGFR-1) was relatively higher than
that of control group (P < 0.05) and there were significant differences between
the groups of the mild preeclampsia, severe preeclampsia and eclampsia (P <
0.05). CONCLUSIONS: (1) The serum sVEGFR-1 levels of preeclampsia groups were
relatively higher than those of control group, the VEGFR-1 may be related to
preeclampsia. (2) The contents of membrane-bound VEGFR-1 in placenta of
preeclampsia groups were relatively lower than that of control group, the
membrane-bound VEGFR-1 may relate to preeclampsia. (3) The ratio of the sVEGFR-1
concentration in serum and the membrane-bound VEGFR-1 contents in placenta of
preeclampsia groups (sVEGFR-1/membrane-bound VEGFR-1) was relatively higher than
that of control group, the preeclampsia may contribute to VEGFR-1/ PLGF and
sVEGFR-1/membrane-bound.
PMID- 17037746
TI - [TRAIL impacts in growth and apoptosis of human ovarian carcinoma cell line
SKOV3].
AB - OBJECTIVE: To investigate the effect of TRAIL on growth and apoptosis of ovarian
carcinoma cell line SKOV3. METHODS: The effects of TRAIL alone and/or associating
with DDP to treat on SKOV3 cells growth inhibition were measured by MTT assay,
and the changes of DR4 and DR5 mRNA were detected by RT-PCR technique. The cell
cycle and apoptosis index were analyzed by technique of Flow Cytometry (FCM).
RESULTS: The soluble TRAIL protein had the inhibiting effect on the growth SKOV3
cells. The DDP increased the ability of TRAIL to SKOV3 cell growth inhibition.
The apoptotic indexes (AI) of SKOV3 cells detected by FCM were 5.9%, 13.4% and
39.5% for control group, TRAIL group and TRAIL plus DDP group, respectively. The
DDP increased the DR5 expressing in SKOV3 cells by 1.95 folds than control group
and by 1.54 times for the DR4 expressing than the control group (P < 0.05).
CONCLUSIONS: The soluble TRAIL has the effect on inhibiting the growth of SKOV3
cells. The combination use of TRAIL and DDP increases significantly the growth
inhibiting ratio to SKOV3 cells. The AI of SKOV3 cell is raised after TRAIL
intervening in. The DDP can increase the expressions of DR4 and DR5 in SKOV3
cells.
PMID- 17037748
TI - [Expression and localization of estrogen receptor ERalpha and the kinds of ERbeta
mRNA on placenta].
AB - OBJECTIVE: To investigate the kinds of ERa, ERbeta mRNA and the localization of
ERa, ERbeta on normal human placenta. METHODS: The expression and localization of
ERa,ERbeta on normal human placenta were detected by reverse transcription
ploymerase chain reaction (RT-PCR) and immunhistochemistry (SP-assay). RESULTS:
There was mRNA expression of ERalpha and ERbeta on human term placenta, and
ERbeta was identified with ERbeta5. The ERa immunoreactivity on human term
placenta was in villous cytotrophoblastic nucleus, and that of ERbeta was in
syncytiotrophoblastic cytoplasm. CONCLUSION: The findings indicate that ERbeta5
is the kind of ERbeta on placenta. It is localizated in the cytoplasm of
syncytiotrophoblast and is probably connected with the production of estrogen.
PMID- 17037749
TI - [Influence of blockade of costimulation on Th1/Th2 cytokines shift in unexplained
early recurrent spontaneous].
AB - OBJECTIVE: To assess the influence of blockade of costimulation on Th1/Th2
Cytokines shift in unexplained early recurrent spontaneous abortion (URSA).
METHODS: The levels of IL-2, IFN-gamma and IL-4 were determined by ELISA in the
supernatant of cultured maternal peripheral blood mononuclear cells (PBMC) from
30 patients of URSA. Cytokine synthesis was induced by activation with antigens
from a choriocarcinomer cell line of JEG-3, with CTLA4Ig at concentrations of 10
microg/mL and 1 microg/mL (experiment groups), or with IgG at the same
concentrations (control groups). RESULTS: The CTLA4Ig groups showed significantly
higher levels of Th2 cytokines IL-4 (P < 0.05), lower levels of Th1 cytokines IL
2 (P < 0.05) and the same levels of IFN-gamma (P > 0.05), compared with the
control groups of the same concentrations respectively. The same results were
found between the experiment groups of different concentration. CONCLUSION:
CTLA4Ig could switch T cell responses from Th1 to Th2 in URSA by blockade of
CD80/CD86 costimulation.
PMID- 17037750
TI - [Comparative research on the implantation of mouse blastocyst in the co-cultural
system of malignant tumor Cells and receptive endometrium in vitro].
AB - OBJECTIVE: Comparaticely to study biological behaviour variability of mouse
embryo implantation in vitro between malignant tumor cells and receptive
endometrium, on the basis of the co-culture of mouse blastocyst and malignant
tumor cells in vitro. METHODS: The light scope, scanning electron scope, the HE
and immunohistochemical staining were applied to investigate and observe the
blastocyst biology behavior in co-cultural system in vitro of mouse blastocyst
malignant cell and blastocyst-monolayer receptive endometrium. RESULTS: There was
no significant biological behaviors observed or discovered for mouse blastocysts
to implant into co-cultural system with malignant tumor cells from different
histologcial origins, and no significant rates obtained for hatchment, attachment
and outgrowth of mouse blastocysts in the co-culture system (P > 0.05) of
monolayer receptival endometrium cells and malignant tumor cells. There was no
significant difference observed between the cell morphology changes of implanted
in endometrium and MMP-9 expressed in trophoblastic cells. CONCLUSIONS: That the
mouse blastocyst cells has no biological behaviour difference happened between
two co-cultural systems in vitro indicates it may be relevant with its high
adaptation to environment and self assembly of the early life.
PMID- 17037751
TI - [A study of genetic diversity in lactate dehydrogenase of Streptococcus mutans
from clinical isolates].
AB - OBJECTIVES: Lactate dehydrogenase (LDH) is shown to be an important virulence
factor resulting in acid production of Streptococcus mutans (S. mutans), on which
the cariogenic potential of S. mutans depends. Differences in cariogenic
abilities of S. mutans isolates may be determined by genetic heterogeneity from
virulent factors. The relationship between LDH activity or genetic diversity and
cariogenicity of S. mutans (serotype c) isolates was studied in this research.
METHODS: The genome DNA of S. mutans isolates were isolated and LDH gene (ldh)
were amplified with specific primers. These isolates came from 34 caries-active
individuals and 36 caries-free ones, in which 24 strains showed the high LDH
activity and 21 strains showed the low LDH activity. Then genetic diversity of
PCR products were analyzed or assessed by restriction fragment-length
polymorphism (RFLP). Some of amplified LDH genes from different group were
sequenced and assayed. RESULTS: It is testified that two genotypes A and B of ldh
RFLP were revealed when LDH genes were digested with Mse I, but Hph I, Mnl I, Dde
I, Nla III and Alu I digesting fragments of Idh gene did not show different
pattern. Furthermore, Fisher Exact one-Tail Test showed that the proportion of
genotype B among strains from caries-free individuals was higher than that from
caries-active ones (P = 0.033), while the distribution of genotypes with
different LDH activity was different between two groups (two-Tail Test P =
0.017). The sequencing DNA testified that the specific base mutation would lead
to multiple kind of genotype resulted. CONCLUSION: This study indicated that LDH
gene of S. mutans clinical strains from different individuals is conservative,
while there still is the gene mutation in. The ldh genetic diversity may be
related to the low caries sensitivity, and closely correlated with the
differences in LDH enzyme activity of S. mutans strains.
PMID- 17037752
TI - [Study on the distribution of lactase in the small intestine of SD rats].
AB - OBJECTIVE: The article deals with the study on the distribution of lactase and
its mRNA in the SD rat intestine. METHODS: 15 of the 3-4 wk old SD rats were
selected for this research project. From SD rat duodenum, we scissored the small
intestine into 3 segments of each 10 cm length to determine the lactase
activities and mRNA levels. RESULTS: The lactase activities of all 3 part
intestines were declined from the duodenum stage by stage (the upper, middle and
lower segment was 0.179, 0.160, or 0.151 U/ml homogenate respectively, P < 0.05),
but there were no significant difference of mRNA levels happening among the 3
groups. CONCLUSION: The results suggest that the lactase activity mainly
distribute over the upper intestine, although there were lactase along whole
intestine.
PMID- 17037753
TI - [Species identification by multiplex amplifying mtDNA-HV I, HV II and cytb
regions].
AB - OBJECTIVE: To evaluate the method for species identification by multiplex
amplification of mtDNA-HV I, HV II and cytb regions. METHODS: The bloodstains or
muscular tissues of human and 16 kinds of animals were collected. DNA were
quantified after extraction. Three pairs of primers were mixed in the same
reaction and the PCR amplification products were analyzed by PAGE and silver
staining. RESULTS: The presence of three bands (278 bp, 358 bp, 425 bp) indicated
the samples were from human, while only one band indicated nonhuman origin. The
position of the animal's only band is different from the band (358 bp) of human.
CONCLUSION: The method of species identification by multiplex amplifying mtDNA-HV
I, HV II and cytb regions is simple and sensitive. It is of use for forensic
identification.
PMID- 17037754
TI - [The tk gene mutation analysis in WTK1 cell line by multiplex PCR].
AB - OBJECTIVE: To explore the tk gene mutation spectrum in spontaneous and induced
WTK1 mutants. METHODS: After exposure to methyl methanesulfonate (MMS), mitomycin
(MMC) or sodiam azide (NaN3), spontaneously-arising and induced mutants of WTK1
cell line were selected. The spectrum and hotspot of tk gene mutation were
analyzed by multiplex PCR. RESULTS: Three chemicals used in this study induced tk
mutation frequency (MF) to increase significantly in a dose-dependent manner;
most of the analyzed mutants had lost exon 4 and exon 5-7. CONCLUSION: Three
chemicals have mutagenic effect on WTK1 cell line, and obvious hotspot exists in
tk gene mutation.
PMID- 17037755
TI - [Study on degradation kinetics or potassium dehydroandrographolidi succinas].
AB - OBJECTIVE: To investigate the hydrolytic degradation of the kinetic
characteristics of Potassium Dehydroandrographolidi Succinas (DAS-K) in aqueous
solution. METHODS: The HPLC method was used to determine the degradation kinetic
parameters of DAS-K aqueous solution at different initial concentration,
different pH, different ionic strength. various temperatures and in different
buffer solutions. RESULTS: DAS-K hydrolytic degradation followed first-order
kinetics as measured by HPLC. From pH 8, the hydrolytic degradation rate of DAS-K
markedly increased with pH. DAS-K was unstable in alkaline pH solution. The
species of buffer solutions seem to have different impact on the catalytic
process. The ionic strength did not have significant effect on the stability of
the drug. According to the Arrhenius plot, the dependence of the decomposition on
temperature was a determining factor, the activation energy was estimated to be
95.68 KJ/mol in phosphate buffer solution at pH 8 and temperature from 60 to 90
degrees C. CONCLUSION: It was found that the hydrolytic degradation of DAS-K
complied with first-order kinetics. The rate of hydrolytic degradation of DAS-K
depended on the pH of solution, the buffer concentration, the buffer species and
the temperature. Especially, pH value was an important factor in determining the
rate of the hydrolytic degradation of the drug.
PMID- 17037756
TI - [Analysis of ordinal repeated measures data using generalized estimating
equation].
AB - OBJECTIVE: To explore the application of the generalized estimating equation in
the ordinal repeated measures data and hence provide methodology reference for
the analysis of repeated measures data in the clinical trials. METHODS: An
example was illustrated by modeling generalized estimating equation using the
GENMOD command in comparison with the independent logistic regression. RESULTS:
All parameters and their standard error were estimated, so every factor could be
dealt with intuitive estimation of parameter. The standard errors of coefficients
in generalized estimating equation are generally greater than that in independent
logistic regression. CONCLUSION: Generalized estimating equation can solve the
correlation between the dependent data by using working correlation matrix, and
it can control strata correlation, repeated measures factor and other confounding
factors effectively, so generalized estimating equation provides an effective
method for the ordinal repeated measures data.
PMID- 17037757
TI - [Establishing a real-time PCR assay for anatid herpesvirus 1].
AB - OBJECTIVES: To develop a real-time quantitative PCR assay to detect duck plague
virus (DPV) for the rapid diagnosis of DPV infection, the investigation of its
nosogenesis and the screening of effective antiviral drugs. METHODS: The primer
and probe were designed according to the gene sequence of DPV DNA polymerase
gene. To establish a standard curve, a plasmid containing 125 bp PCR product was
constructed and severed as a positive control. The TaqMan based real-time PCR
method was adopted and compared with the traditional PCR approach in sensitivity,
reliability and specificity. RESULTS: A good linear correlation was demonstrated
in the standard curve for the real-time PCR assay within the range from 2.3 x 10
to 2.3 x 10(5) copies. A minimum of 23 positive plasmids could be detected,
indicating a good sensitivity of the assay. The coefficients of variance (CVs)
were 1.22-6.69 and 2.09-8.84 for the intra-assay and inter-assay tests
respectively, indicating a good reliability. No amplification products were found
for DNA from other pathogens, indicating a good specificity. The comparative
study proved that the TaqMan technology was much more sensitive than traditional
PCR assay. CONCLUSION: The real-time quantitative PCR assay for DPV DNA has good
sensitivity, specificity and reliability.
PMID- 17037758
TI - [Establishment of the guinea pig model of synovial tuberculosis of knee joint by
mycobacterium tuberculosis H37Rv infection].
AB - OBJECTIVE: To explore how to establish the guinea pig model of synovial
tuberculosis of knee joint by mycobacterium tuberculosis H37Rv infection.
METHODS: Two doses (1 x 10(7)/mL, 50 microL and 100 microL) of Mycobacterium
strains were injected into the knee joint of the guinea pig that had been
immunized and allergized with Freund's complete adjuvant six weeks previously.
The pathological changes of the synovial membrane, cartilage and bone after
infection of mycobacterium tuberculosis were investigated. At the same time, the
synovial membrane tissues and culture for the mycobacterium tuberculosis were
collected and examined. RESULTS: After the infection of mycobacterium
tuberculosis H37Rv, the knee joint of guinea pig became swollen, but the
interference to the whole conditions of the guinea pig was slight in both
infection groups. The tissue sections of the synovial membrane showed tubercle
and caseous necrosis of the knee joint in both groups. The mycobacterium
tuberculosis could be detected by using Ziehl-neelsen stain and the culture from
the synovial membrane of the knee joint. CONCLUSION: By injecting suitable dosage
of mycobacterium H37Rv strains into the joint of the immunized and allergized
guinea pig, we have established the guinea pig model of synovial tuberculosis
that is pathologically similar to synovial tuberculosis in humans, so it is fit
for use in the diagnostic studies and pathological researches.
PMID- 17037759
TI - [Obesity and nutrition disorders].
PMID- 17037760
TI - [Bariatric surgery].
PMID- 17037761
TI - [Child nutrition].
PMID- 17037762
TI - [Malabsorption and celiac disease].
PMID- 17037763
TI - [NSAIDs or coxibs: benefits and gastrointestinal vs. cardiovascular effects].
PMID- 17037764
TI - [Gastric cancer].
PMID- 17037766
TI - [Pancreatitis].
PMID- 17037765
TI - H. pylori: scientific basis to patient cure.
PMID- 17037767
TI - [Diagnostic and therapeutic endoscopy of pancreas and biliary tract].
PMID- 17037768
TI - [Gallbladder and Bile Ducts].
PMID- 17037769
TI - [Pancreatic neoplasms].
PMID- 17037770
TI - [Hemostasis in gastrointestinal hemorrhage].
PMID- 17037771
TI - [Endoscopic ultrasound 2006].
PMID- 17037772
TI - [Obscure gastrointestinal bleeding].
PMID- 17037773
TI - [Diagnostic advances in gastroesophageal reflux disease].
PMID- 17037774
TI - [Non-erosive gastroesophageal reflux disease].
PMID- 17037776
TI - [Barrett esophagus].
PMID- 17037775
TI - [Medical therapy of gastroesophageal reflux disease].
PMID- 17037777
TI - [Surgical treatment of gastroesophageal reflux disease].
PMID- 17037778
TI - [Risk reductions in gastroenterology].
PMID- 17037779
TI - [Functional dyspepsia].
PMID- 17037780
TI - [Heartburn and chest pain].
PMID- 17037781
TI - [Irritable bowel syndrome].
PMID- 17037782
TI - [Functional constipation].
PMID- 17037783
TI - [Digestive system functional disorders in children].
PMID- 17037784
TI - [Chronic diarrhea].
PMID- 17037785
TI - [Advances in the use of non-biologic agents in the treatment of inflammatory
bowel diseases].
PMID- 17037786
TI - [Biologic therapy for inflammatory bowel diseases].
PMID- 17037787
TI - [Colorectal cancer].
PMID- 17037788
TI - [Autoimmune hepatitis].
PMID- 17037789
TI - [Hepatitis C and B (HCV, HBV)].
PMID- 17037790
TI - [Non alcoholic fatty liver].
PMID- 17037791
TI - [Liver transplantation update 2005-2006].
PMID- 17037792
TI - [Genomic medicine and hepatology].
PMID- 17037793
TI - [The future of radiology].
PMID- 17037794
TI - [Hepatic insufficiency and related factors].
PMID- 17037795
TI - [Medical therapy of portal hypertension].
PMID- 17037796
TI - [AGA plenaries].
PMID- 17037797
TI - [ASGE pleanry session].
PMID- 17037798
TI - [SSAT plenary session].
PMID- 17037799
TI - [Neonatal mortality in a regional perinatal hospital in Merida, Yucatan, 1995
2004 I. Analysis of the gross, specific rates].
AB - OBJECTIVE: To evaluate the neonatal mortality and the specific neonatal mortality
rates by groups of birthweight and gestacional age, at the Ignacio Garcia Tellez
National Medical Center which is a reference tertiary perinatal center of the
Social Security Mexican Institute for the Yucatan Peninsula, along the period of
1995-2004. MATERIAL AND METHODS: A cohort of 46,297 live newborns was studied
with birtweight of 500 grams or more, that were discharged between January 1st
1995 and December 31st 2004. Birthweight, gestational age, length of
hospitalization, condition at discharge were captured in a data base. Triennial
analysis of mortality was done. RESULTS: The proportion of neonates with
birthweight <2,500 g increased and 19% neonates <1,000 g 50%, the increment was
21% for preterm neonates, 46% for immature, and 40% for those extremely immature.
The early neonatal mortality rate diminished from 7.0 to 6.9, the late mortality
from 3.0 to 2.2, the neonatal from 10.0 to 9.2/1,000 live newborn, the survival
increased 232% in neonates with birthweight between 500-749 g, 25% between 750
999 g, 5.8% between 1,000-1,249 g, 8.2% between 1,250-1,499 g. The neonatal
mortality decreased 31.8% from the expected, because the adjusted neonatal
mortality rate was 13.5 compared with the observed 9.2/1,000 live newborn.
CONCLUSIONS: There was a significant increase of the survival with lesser
birthweight and gestational age, although it was not reflected in the brut
neonatal mortality rate because there was an increase of the risk population.
PMID- 17037800
TI - [Prescription and drug expenditure in gynecology and obstetrics in Northwest
medical units from IMSS].
AB - BACKGROUND: Drug prescription is the most frequent medical intervention in
Gynecology and Obstetrics; however, studies of prescription profile are limited.
In this study, we analyzed differences of expense by drug prescription for
gynecologic and obstetrics health problems. PATIENTS AND METHOD: It was performed
a cross sectional study for one year analysis in each medical area that shape
IMSS western district. We calculated spending and consumption coefficients for
each drug and therapeutic groups. User coefficients were ordered to compare
consumption differences. Besides the statistical ratio of consumption between
drugs groups, we described the differences found and analyzed the prescription
profile among medical regions. RESULTS: Data related to the expenses in each one
of the regions show important differences in each one of the drugs and
therapeutic groups. The most common expense for drugs is related to the treatment
of osteoporosis, menopause and fertility problems. We also found differences in
prescription drug preferences in each therapeutic subgroup. DISCUSSION: Drug
prescription studies are useful as a basis for further specific studies in each
pharmacologic subgroup. There are few studies that analyze the drug prescription
profile on Gynecology and Obstetrics. In this study it is possible to suppose
that medical prescription was not based on known medical evidences; therefore, we
must reconsider the need of a permanent actualization and systematic medical
evaluation.
PMID- 17037801
TI - [Anal incontinence caused by an obstetric trauma. Experience with the technique
of overlapping sphincteroplasty].
AB - INTRODUCTION: Anal incontinence (IA) could be of idiopathic, congenital,
neurological origin, or secondary to trauma. Obstetric trauma is the most common
cause of the traumatic anal incontinence. OBJECTIVE: To analyze results of a
group of patients with anal incontinence secondary to obstetric trauma, with
overlapping sphincteroplasty. PATIENTS AND METHODS: All patients with anal
incontinence secondary to obstetric trauma without neurological damage, between
January 2002 to January 2006 were studied; all of them underwent overlapping
sphincteroplasty. We evaluated improvement in incontinence score according Jorge
and Wexner incontinence scale, pre and postoperatively as well as morbi-mortality
rates. RESULTS: 16 patients, most of them with total anal incontinence, with
preoperative values between 16 to 20 points at the Jorge and Wexner scale; 14
patients (87.5%) referred improvement in their values with 4 to 0 points
postoperatively, two patients did not refer significant improvement, both of them
with defects in both sphincters and loss of the 50% of the entire sphincteric
complex. They were sent to bio-feedback therapy. There was not mortality. Seven
patients (43.7%) had skin dehiscence. CONCLUSIONS: Overlapping sphincteroplasty
is an accurately technique for repair obstetric trauma injuries of the anal
sphincter, with a success rate of 70 to 80%, and a low morbidity rate.
PMID- 17037802
TI - [Mozart's music in the prenatal period].
AB - Diverse studies demonstrate that the future baby reacts to the sounds and the
light in uterus four months before being born, that is to say, he is able to
recognize stimulus which was exposed habitually, like the beats of the mothers
heart and the voice of the same one when talk him before being born, likewise the
music he used to heard during pregnancy. The babies who through their mother
listened to music of Mozart in uterus and return it to listen in the delivery
room of when they are born feel greater tranquility and less aggressiveness.
Mozart was a genius and the most beautiful from it is the so important impact in
the cognitive development, social and affective of those who are exposed to the
wonderful sounds and rythm of music from the maternal belly. The previous thing
is based on experiments scientifically controlled that revalue the communication
between the mother and the future baby as well as the importance of this link.
PMID- 17037803
TI - [Physician-patient relationship: a forgotten need?].
AB - The medical-patient relation has a big weight in the medical practice. There have
been different medical codes that highlight the importance of this relation and
the existence of the patient's rights; nevertheless, its repercussion has been
scarce. A few time ago, this relation was established among a clear binomial: the
doctor and the patient, but now this binomial is very complex and it seems to
have disappeared. The main models of the medical-patient relation are: Activity
Passiveness, Guide-Cooperation, and Participation. Currently, the medical-patient
relation has been deteriorated because it was interfered by external factors,
such as: socioeconomic problems, those due to the technological development and
those attributable to the doctor's conduct. It seems fundamental to recover this
relation, as a part of the medical art. The solution is not easy and involves the
need to count with legal mechanisms that protect the doctors and patients rights.
Besides, it will be important to carry out deep changes in the models of health
education. If the medical-patient relation is not prioritized as an important
part of the medical exercise, our profession would face the risk of only becoming
a technical occupation.
PMID- 17037804
TI - [Uterine and jejunum perforation due to intrauterine device. A report of a case
and literature review].
AB - The application of a copper IUD can perforate completely the uterus and involve
adjacent organs such as the bladder, small bowel, colon, rectum or appendix. Once
the diagnosis is established, complete extraction must follow. We present a case
report of a 33 year-old patient in which a copper IUD was placed in a medical
office, three months after a third cesarean, without history of sepsis. Ninety
days after placement, the patient complained of menstrual irregularities
(opsomenhorrea) without any other symptoms. On physical examination with
speculum, the IUD's guide strings were not visible; a transvaginal USG was
performed without visualization of the IUD in the uterine cavity. An abdominal
CAT scan showed the presence of the IUD outside the uterus. Hysteroscopy
laparoscopy was performed with transoperatory fluoroscopy, which revealed the
copper IUD inside the yeyunum, a complete extraction followed with entero-entero
anastomosis. This case will show that IUD placement is not innocuous and that
adjacent organ damage must always be considered and resolved immediately.
PMID- 17037805
TI - [Ectopia cordis: multidisciplinary approach with successful result].
AB - Ectopia cordis is a pathology in which the heart is complete or partially outside
of the thoracic cavity. It represents a challenge for the diagnosis and handling
because of its high perinatal mortality. We present the first case of thoracic
ectopia cordis with prenatal diagnostic (27th week), its multidisciplinary
handling at Hospital de Ginecopediatria num. 71 of the Centro Medico Nacional
Adolfo Ruiz Cortines, IMSS, in Veracruz, Mexico. We communicate the case of a 24
year-old woman referred by her correspondent medical unit with the diagnosis of
23.6 weeks pregnancy with suspicion of heart malformation by ultrasound. The
pregnancy was followed-up until the 38th week, when it was programmed a caesarean
section. The newborn had ectopia cordis, which was treated at the moment of
birth. In this article, we present pictures of the heart defect as well as its
evolution. The up-to-date bibliography is revised about the medical profile and
treatment. The handling of the ectopia cordis includes an appropriate prenatal
diagnosis through echocardiograph, a multidisciplinary perinatal team, to program
the caesarean operation, aseptic handling of the newborn, immediate correction of
the wall defect with skin torn piece without trying to correct the costal grill,
specific hemodynamic cares, to reprogramme a correction of associated defects.
PMID- 17037806
TI - [Clinical results of the use of high doses of diethylstilbestrol on abortion
threat. 1951].
PMID- 17037807
TI - [Working memory: neuropsychological and neurobiological issues].
AB - Working memory denotes an ability to remember information for a short-time and to
manipulate it. The memory allows including correct information depending on the
situation, to keep the information on present activities for a while and enables
changing the reaction according to new criteria. The relation between working
memory and efficiency of complex cognitive processes and also with the control of
emotional processes, plasticity of behaviour and consciousness was demonstrated.
Working memory is connected with the activity of the dorsolateral prefrontal
cortex of the brain. Recently, it has been shown, that working memory
disturbances play an important role in the aetiopathogenesis of psychiatric
disturbances such as schizophrenia, bipolar affective disorder or obsessive
compulsive disorder. Working memory disturbances are also shown in a proportion
of healthy first-degree relatives of patients with schizophrenia or bipolar
disorders. Working memory disturbances are presently regarded as a cognitive
endophenotypic marker of vulnerability to these illnesses. In recent years, an
association between working memory abilities and activity of different
neurotransmitters, especially with the dopaminergic system in the brain, has been
shown. Molecular genetic studies show an association between working memory
abilities and polymorphism of the dopaminergic system genes in schizophrenia and
polymorphism of BDNF gene in bipolar affective disorders. So far not much data
about the genetics of working memory in healthy subjects has been gathered.
Currently in Poland such research is carried on in the Clinical Neuropsychology
Unit Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz in
cooperation with the Department of Adult Psychiatry and Laboratory of Psychiatric
Genetics University of Medical Sciences in Poznan.
PMID- 17037808
TI - [Evolutionary concepts of affective disorders].
AB - Mood may be considered the module of the human mind, which has evolved to tune
the activity ofthe organism to the specific environmental conditions in a better
way. In some cases depression may be adaptive, for example in aborting the
activity associated with too many obstacles. At the same time hypomania may be
related to the capability of mobilising the organism to gain many resources in a
short period of time. Severe mood disorders may be related to the genetic
variants, eg. of the serotonin transporter or brain-derived neurotrophic factor,
which in several situations may give some evolutionary advantage. Affective
temperaments, observed in the relatives of patients with affective disorders may
be associated with some benefits in the social life. The relationship between
early adversities and adult depression may be related to the phenomenon of the
stress axis programming, which has deep evolutionary roots. Some infectious
factors may cause behaviours similar to the affective symptoms, which may
increase their reproductive success. The evolutionary perspective, which is
complementary to the current etiopathogenic theories may help in understanding,
why genes and traits which
PMID- 17037809
TI - [Serotoninergic system and limbic-hypothalamic-pituitary-adrenal axis (LHPA axis)
in depression].
AB - Depression is associated with the dysfunction in the serotoninergic (5-HT, 5
hydroxytryptamine) transmission and dysregulation of the limbic-hypothalamic
pituitary-adrenal axis (LHPA axis). In depression, the 5-HT system exhibits
impaired presynaptic activity of 5-HT neurones, an increased activity of central
postsynaptic 5-HT2A receptors, decreased activity of postsynaptic 5-HT1A
receptors and altered synaptic 5-HT uptake. The coexistent dysregulation of the
LHPA axis is predominantly linked to GR (glucocorticoid receptor) dysfunction
within the limbic system along with hypercortisolemia, MR (mineralocorticoid
receptor) and GR receptors imbalance which results in impaired negative feedback
mechanisms in the LHPA axis loops. Several clinical and animal studies revealed
the involvement of 5-HT1A system in LHPA axis regulatory mechanisms. That
association seems to be dependent on the corticoid levels. The impaired GR
receptor function and MR/GR receptors imbalance alter the negative feedback
regulation within the LHPA axis which is followed by its dysregulation and
hypercortisolemia that is further associated with the decreased activity of
postsynaptic 5-HT1A receptors resulting in a serotoninergic dysfunction. The aim
of this paper is to discuss and review the current data on the existence of the
hypothetical relationship between the activity of the serotoninergic system,
predominantly 5-HT1A receptors, and LHPA axis in depression.
PMID- 17037810
TI - [Indicators of the persistent pro-inflammatory activation of the immune system in
depression].
AB - The aetiology of depression remains tentative. Current hypotheses on the
aetiology of the depressive disorder tend to integrate monoaminoergic,
neuroendocrine and immunological concepts of depression. A number of research
papers emphasise the altered hormonal and immune status of patients with
depression with pronounced cytokine level variations. Those studies tend to link
the variable course of depression in relation to the altered proinflammatory
activity of the immune system. The results of the studies on the activity of the
selected elements of the immune system are ambiguous indicating both increased
and decreased activities of its selected elements. However, a number of basic and
psychopharmacological studies support the hypothesis of the increased
proinflammatory activity of the immune system in the course of depression which
is the foundation for the immunological hypothesis of depression. The aim of this
paper is to review the functional abnormalities that are observed in depression
focusing on the monoaminoergic deficiency and increased immune activation as well
as endocrine dysregulation. This paper puts together and discusses current
studies related to this subject with a detailed insight into interactions
involving nervous, endocrine and immune systems.
PMID- 17037811
TI - [The probability of bipolarity among patients with recurrent depressive
disorder].
AB - Over the last few years researchers have paid a lot of attention to the problem
of the correct diagnosis of affective disorders. Propositions have appeared
regarding the widening of the officially accepted criteria to be used in
diagnosis. AIM: The aim of the study was to assess the probability of various
types of bipolar affective disorders (type 1 and 2 CHAD, as well as spectrum)
among patients (n = 246) treated for recurrent depressive disorder (CHAJ).
METHOD: The analysis was based on the broadened criteria for affective disorders
introduced by Ghaemi et al. and Hirschfield's Questionnaire on affective
disorders. RESULTS: The appearance in the past of strange, risky behaviour was
associated with a greater risk of type 1 CHAD in comparison to CHAJ (OR=24.5), as
did extreme, irrational expenditure (OR=21. 1), a lack of criticism with respect
to one's own social behaviour (OR=20.3), increased interest in sex (OR=17.7), as
well as extreme self confidence (OR=12). A lack of criticism with respect to
one's own social behaviour and strange, risky behaviour was associated with a
greater risk of type 2 CHAD (OR=12.7 and OR=10, respectively). The greatest risk
of spectrum CHAD type disorders were associated with hypomania, including drug
induced (OR=15.8). as well as a lack of criticism with respect to one's own
social behaviour (OR=11.8). Panic attacks appeared more often in bipolar
affective disorders in comparison to recurring depressive disorders, but their
frequency was similar in all three groups (CHAD-I, CHAD-II, CHAD-S). The early
occurrence of depression (before 25 years of age) increased the risk of each of
the three types of bipolar affective disorders significantly (by a factor of 3 to
5). CONCLUSIONS: The findings indicate the necessity of discussion on sharp
criteria of bipolar affective disorders. The results should be helpful in the
diagnosis of such disorders, which could have important consequences for
effective therapy.
PMID- 17037812
TI - [Comorbidity of eating disorders and bipolar affective disorders].
AB - Eating disorders--anorexia nervosa, bulimia nervosa and eating disorders not
otherwise specified (EDNOS) occur usually in young females. The significant
pathogenic differences between patients who only restrict food, and patients with
binge eating and compensatory behaviours, such as vomiting and purging were
described. The prevalence of bipolar affective disorders--especially bipolar II
and bipolar spectrum disorders (BS) may reach 5% in the general population. About
half of the depressive episodes are associated with a "mild" bipolar disorder,
and such a diagnosis is suggested by impulsivity and mood-instability.
Previously, majority of research on the comorbidity between eating and affective
disorders focused on depressive symptomatology, however difficulties in the
reliable assessment of hypomania may obfuscate the estimation of the co
occurrence of eating disorders with BS. Epidemiological studies suggest the
association between BS and eating disorders with binge episodes (bulimia nervosa,
anorexia- bulimic type and EDNOS with binge episodes). Co-occurrence of such
disorders with depressive symptoms probably suggests the diagnosis of BS, not
recurrent depression. Bulimic behaviours, impulsivity and affective disorders
might be related to the impairment of the serotonergic neurotransmission, which
may result from the genetic vulnerability and early life trauma. Currently, the
first-line pharmacological treatment of co-occurring eating disorders with binge
episodes and BS are selective serotonin reuptake inhibitors. However in some
cases, the use of mood-stabilising agents as monotherapy or in combination with
serotonergic drugs may be helpful.
PMID- 17037813
TI - [Point prevalence of depression in the Cracow population of 13 year old students
in 1984 and 2001].
AB - Results of scarce epidemiological studies on depression in adolescents are
diverse and dependent of survey methodology as well as on the theoretical
approach of research. Those studies where the methods are comparable show that
depression prevalence depends on the macrosocial situation and the adolescence
stage. AIM: The study aimed to assess changes in depression prevalence in mid
adolescents between 1984 and 2001. A presumption was made that the social
situation in Poland had changed in the last 17 years. METHOD: In 2001 a
representative sample of school attending 13 y.o. adolescents was screened with
KID-IO "B1". The results were compared with those of a similar survey, using the
same method, carried out in 1984. RESULTS: Point prevalence index in 2001
appeared to be lower than in the survey in 1984 (24.6% versus 31.6%). This
resulted exclusively from a significant decrease in depression among girls (26.8%
versus 42.2%). CONCLUSION: The obtained data allows for an interpretation of the
findings as being a result of macrosocial changes. Other hypotheses e.g.
influence of the adolescence timing and course requires a longitudinal
prospective study.
PMID- 17037814
TI - [Prospective studies on dynamics of depression from preadolescence to early
adolescence].
AB - AIM: The aim of the study is to evaluate the changes in prevalence and dynamics
of depression during puberty. It was conducted in prospective studies in a
representative group of large-town primary school students. METHOD: A group of
1993, 10 year-old students were chosen in a two-stage draw. They were studied
with the Karkow Depression Inwentory (KID) in the subsequent years 2001, 2002,
2003. RESULTS: The point prevalence of depression was respectively 29%, 30% and
26% for 10, 11 and 12 year-olds. The spread-out rate of depressive disorder was
relatively stable. CONCLUSIONS: Depression is more common in pre-adolescent boys
than girls. The dynamics of the disorder, when studied in these three years show
that depression is a disorder with a very unequivocal course amongst the
preadolescents.
PMID- 17037815
TI - [Coping with stress strategies among female patients suffering from a
depression].
AB - INTRODUCTION: Within the past few years there was an ever increasing number of
scientific publications focusing on the question of stress, new theories were
created as well as efforts were taken to classify them. According to stress
researchers, finding out how to manage with stress and with difficulties (the
strategy of coping) plays an even more important role than the phenomenon of
stress itself. This is due to the fact that the former decides about the quality
of one's life. Stressful transactions in the aspect of a disease seem to differ
from everyday stressful problems. The intensity of stress and the capability of
taking control over stress itself are different in the case of a danger of
disease compared to an experience of disease, which influences applying certain
coping strategies (task-aimed strategies). AIM: The purpose the study was to
determine the relationship between the social functioning of female patients
suffering from depression with their coping style. METHOD: 60 female patients
with a diagnosed depression and 60 mentally ordered female patients were tested
with the use of Endler's and Parker's Coping Inventory for Stressful Situations
Questionnaire (CISS). RESULTS: The study presents and describes the result of the
research concerning female patients suffering from depression. The analysis of
the results indicated the existence of differences in choosing coping strategies
(task-aimed strategies) in both the studied groups of women. CONCLUSIONS: The
study shows that female patients with depression cope with stress mostly using
emotional strategies, and the avoidance strategies are used the least often.
Mentally ordered women however, most commonly use problem (task)-focused
strategies.
PMID- 17037816
TI - [The level of social support parameters in relation to coping with stress caused
by a disease among female patients suffering from depression].
AB - INTRODUCTION: Social support issues have their permanent position in the studies
of socio-psychological changes influencing people's health. Social support has
been treated as one of the factors guarding against disease symptoms occurrence
and supporting the stable health state. AIM: The purpose the study was to
determine how female patients suffering from depression function in society in
relation to the social support they receive. METHOD: 60 female patients with a
diagnosed depression and 60 mentally ordered female patients were tested with the
use of Uchnast's Sense of Security Questionnaire (KPB). The social support
aspects such as the sense of security, sense of closeness, stability and self
confidence were analysed. The participants of the analysis were both women with
diagnosed depression and women without any indicators of a depression. RESULTS:
The analysis of the result indicated the existence of differences in the
intensity of all the social support parameters in both studied groups of women.
CONCLUSIONS: Women with depression are characterised by a lower sense of
closeness, lower stability and lower self-confidence. Among the female patients
with depression there is a lower level of the need of safety, and this is the
symptom characteristic for the individuals not properly adjusted to social
conditions. Lower sense of security staunches and deteriorates the perception of
social support, both perceived and expected.
PMID- 17037817
TI - [The eclectic individual psychotherapy of a dysthymic patient--case study].
AB - The article describes the case of eclectic individual psychotherapy of a
dysthymic patient. The therapeutic process integrated elements of the following
psychotherapeutic approaches: psychodynamic, behavioural-cognitive, systemic,
interpersonal, existential and Gestalt. The paper discusses history of treatment,
diagnosis of dysthymia, indications for psychotherapy, course of the sessions.
Anamnesis, factors contributing to the disorder, triggers and factors sustaining
the symptoms, personality factors were also analysed. Therapeutic goals and
applied techniques are presented.
PMID- 17037818
TI - [The stroke variables assessment as a prognostic factor for post-stroke
depression with the emphasis on the cerebral SPECT regional blood flow
asymmetry].
AB - AIM: The aim of this paper was to assess the risk for depression in a 6-month
long post stroke follow up period as related to the stroke variables (i.e. stroke
localisation, haemodynamic parameters). METHOD: The stroke localisation was
determined with CT and/or MRI. Subsequently all the examined individuals
underwent SPECT examination. The follow up examinations were performed by the
consultant psychiatrist in 6, 12 and 24 weeks subsequent to the stroke episode.
The depressive episode diagnosis was established on the basis of ICD-10
diagnostic criteria. RESULTS: Only right-handed patients (43 men aged 57.3 +/-
11.6 and 17 women aged 62.5 +/- 14.4) with unilateral brain lesion were examined.
23 subjects (38%) developed depression in the follow-up period. 5 women (29%) and
18 men (ca. 42%) developed a depressive episode. Only one of the observed
depressive episodes met ICD-10 criteria for severe depressive episode. 10
patients suffered from moderate depressive episode and 12 subjects exhibited a
mild depressive episode. CONCLUSIONS: The results obtained with CT and/or MRI
techniques revealed no correlation between the post-stroke depression and stroke
lateralisation. However the localisation of the deep brain functional
abnormalities revealed with SPECT correlated with the occurrence of the affective
disorders as related to the asymmetry in regional blood flow measures.
PMID- 17037819
TI - [Changes of coefficients of sleep onset, sleep maintenance and awakenings in most
common psychiatric disorders in inpatients].
AB - INTRODUCTION: The study's purpose was to find differences of selected
psychopathological syndromes according to characteristic disturbances of sleep
which are present in them. METHODS: Among 194 patients (mean age: 42.27 +/-
14.15) 108 were women (mean age: 42.97 +/- 14.13) and 86 were men (mean age:
41.38 +/- 14.22). Psychiatric examination and sleep disturbance evaluation was
done with the use of our own questionnaire: Multidimensional System for
Evaluation of Sleep Disorders (MSESD) were performed the third day after
admission to a psychiatric ward. Sleep was analysed according to coefficients
which described falling asleep, sleep maintenance and awakenings. These
coefficients were created according to parameters obtained from MSESD. RESULTS:
Coefficients obtained from the "schizophrenic disorders" and "personality
disorders" groups did not differ significantly from the average coefficients for
all the patients. The common feature among other groups of patients was the
elevation of the coefficient of falling asleep especially for the "organic" and
"depressive" disorders groups. The most pronounced elevation of the falling
asleep coefficient was detected in the "depression without somatic features"
group, however this elevation was also clearly seen in the "reactive disorders"
group. In the latter group all other coefficients were also significantly
elevated. CONCLUSIONS: Constructed coefficients of sleep disturbances may be
useful for diagnosing and differentiating the most often psychiatric disorders in
inpatients.
PMID- 17037820
TI - [Pharmacological treatment of insomnia].
AB - Sleep disturbances of insomnia type belong to the most common health problems of
the modern society. Chronic insomnia, one that worsens daytime functioning and
lasts over one month, occurs in 9 to 15% of the general population of developed
countries. Further 15-20% of the population suffers from short term insomnia.
When approaching a patient with insomnia, the physician should firstly regard
sleep disturbances as a symptom related to other medical conditions. The most
common causes of chronic insomnia include psychiatric disorders, addictions,
somatic disorders and poor sleep habits. For successful treatment of insomnia it
is most important to diagnose the cause of sleep problems properly. Such
management of sleep disturbances allows treating insomnia causally. The
symptomatic treatment of insomnia includes sleep hygiene and intermittent
administration of sleep promoting drugs such as benzodiazepines, non
benzodiazepine hypnotics of second generation, antidepressants, antipsychotics,
antihistaminics or herbal and over the counter agents. This article reviews the
sleep promoting drugs and substances that can be used for treatment of chronic
insomnia.
PMID- 17037821
TI - [A double-blind controlled study of the efficacy and acceptability of tianeptine
in comparison with fluvoxamine in the treatment of depressed alcoholic patients].
AB - AIM: The main objective of the study was the evaluation of therapeutic efficacy
of tianeptine (T) (37.5 mg/day) in comparison with fluvoxamine (F) (100 mg/day)
in depressed patients with alcohol dependence or harmful use who had abstained
from alcohol, in a 6-week treatment period. The secondary objectives were the
assessment of the acceptability of both drugs and analysis of the alcohol craving
behaviour regarding both treatments. METHOD: Outpatients who met ICD-10 criteria
for depression and alcohol dependence or harmful use were randomised to a double
blind 6-week comparative trail. Responders (50% or more reduction in baseline
HDRS) were proposed to continue the same treatment up to 90 days. The
antidepressant efficacy was assessed with the use of the HDRS (main criterion).
Other scales used in the study were HARS, CGI and OCDS. Tolerance was evaluated
by monitoring of adverse events. RESULTS: A total of 298 (150 in T group and 148
in F group) were randomized. Both drugs showed good efficacy in the treatment of
depressive symptoms. In Full Analysis Set (FAS) mean HDRS score significantly
decreased in both groups from 22.2 at baseline to 10.6 at end-point in T group
and from 21.8 to 11.4 in F group. There was no statistical difference between
groups. The number of patients found to be responders at end-point was 72.1% in
the T group and 67.1% in the F group. There was significant improvement in both
treatment groups in HARS and CGI. Also analysis of alcohol craving by the OCDS
scale showed significant improvement in both groups. No significant difference
between treatment groups regarding those scales was noted. In a 6-week treatment
period, statistically significantly more patients continued the study in the T
group. Tolerability of both drugs was good. 16.7% of the patients experienced at
least one adverse event in the T group and 20.3% in the F group. CONCLUSION:
Tianeptine and fluvoxamine are effective and safe in the treatment of depression
in the group of patients with alcohol dependence.
PMID- 17037822
TI - [New and traditional laboratory markers of alcohol abuse in hospitalized alcohol
dependent men].
AB - AIM: Evaluation of the diagnostic value (sensitivity, specificity and accuracy)
of the new-carbohydrate-deficient transferrin (CDT), sialic acid (SA) and
traditional (GGT, AST, ALT and MCV) markers of alcohol abuse in alcohol dependent
men irrespective of the time of abstinence. METHOD: 75 alcohol dependent men
admitted for treatment have been tested. The examination was performed twice:
upon admission to the hospital and after 3 weeks of hospitalization. CDT was
estimated using an immunoturbidimetric assay after anion-exchange chromatography
and sialic acid by the enzymatic colorimetric method. The diagnostic accuracy was
calculated as the area under the ROC curve (AUC). RESULTS: At the time of
admission to hospital, the values of CDT and sialic acid were elevated in
comparison with the control group, similarly as with the traditional tests. After
3 weeks of hospitalization all test results decreased. CDT correlated positively
with AST and sialic acid with ALT and GGT. The highest diagnostic accuracy was
obtained for CDT (AUC=0.89). The diagnostic accuracy of sialic acid was lower
than MCV, GGT and AST, but the same as ALT (AUC=0.66). CONCLUSIONS: CDT exhibits
the highest diagnostic usefulness for alcohol abuse in alcohol dependent men in
different time of abstinence. The tests with high diagnostic accuracy (CDT, MCV
and GGT) are still useful after 3 weeks of hospitalization (abstinence), when the
remaining tests are normalized.
PMID- 17037823
TI - [Private and public self-awareness changes in psychotherapy of alcohol-addicted
felons].
AB - AIM: Testing effectiveness of psychotherapy by evaluating changes in private and
public self-consciousness of alcohol addicted persons and imprisoned felons.
METHOD: The questionnaire known as Self-Consiousness Scale Fenigstein, Scheier,
Buss's was applied. The tool is based on the theory of Duval and Wicklund and
that of Carver and Scheier. Treatment curriculum--was based on two models of
alcohol addiction. the psychological one and the other derived of assumptions
defined in the Alcoholics Anonymous movement. RESULTS: In the course of the
psychotherapeutic treatment--discordantly with prior research expectations-
neither the so-called private nor the public self-consciousness changed. In turn,
as hypothesised, social anxiety decreased significantly. CONCLUSIONS: 1. Decrease
of social anxiety shows effectiveness of the therapeutic approach, which is
higher than that of the sole Alcoholics Anonymous programme. 2. Further research
should be focused on refinement of both the tool measuring self-consciousness
changes and some elements of the therapeutic agenda.
PMID- 17037824
TI - [Security measures in the penal code, in the opinions of expert psychiatrists and
some problems in their applications].
AB - The aim of this paper is to remind expert psychiatrists, the three basic elements
required for the application of security measures such as placing the convict in
a psychiatric hospital. They are: 1) An act was of serious social damage, 2) the
damage was committed in a state of non-liability, 3) there is a high risk of the
person repeating the act of similar social damage. The fulfilment of these three
is an obligation for the court to apply the security measure of placing the
person in a psychiatric hospital (art. 94 section 1 of the penal code). Practice
shows that experts have difficulties in these evaluations, which in turn results
in faults in directing for placement withoutjust cause, or in turn-there is no
directing, even though there are causes for it. There is a huge need for legal
regulations on these manners, after the forensic psychiatric observation ends.
The non-liable delinquent who committed an act of serious social damage is in
risk of committing this act once more, whilst he is not in custody. The issue is
in showing a legal basis for keeping the non-liable delinquent from such an act
in a psychiatric hospital, in spite of ending the observation, until the legal
sentence on the security measure is in place.
PMID- 17037825
TI - Charity with an arm twist. Senate hearing starts the ball rolling on tougher
community benefits standard, greater federal oversight of not-for-profits.
AB - A Senate hearing last week helped boost not-for-profit hospitals' chances of
facing a new standard for reporting community benefits. At stake for hospitals
are billions in tax breaks. The standard for exemption hasn't been modified since
1969, and "has not kept up with the substantial unfunded health needs of
communities," says Nancy Kane, right, a member of MedPAC.
PMID- 17037826
TI - Executive privilege. Club dues called business expense.
PMID- 17037827
TI - AHA: transparency our way OK. Association backs bill similar to its initial
proposal.
PMID- 17037828
TI - Questioning technology. Calif. Blues' foundation grant spearheads research.
PMID- 17037829
TI - The bash brothers. Grassley, Stark wasting capital with continuous attacks on
providers.
PMID- 17037830
TI - 2006 up and comers. Twelve young leaders use their energy and enthusiasm to make
a difference.
PMID- 17037831
TI - Nanostructured biofilms and biocrystals.
AB - The design, the physical properties and the implementation of nanostructured
protein biofilms and nanostructured biocrystals are here summarized from ab
initio considerations. Particular emphasis is placed on those being developed in
our Institute having unique properties useful in a wide range of applications.
PMID- 17037832
TI - Nanopatterns with biological functions.
AB - Both curiosity and a desire for efficiency have advanced our ability to
manipulate materials with great precision on the micrometer and, more recently,
on the nanometer scale. Certainly, the semiconductor and integrated circuit
industry has put the pressure on scientist and engineers to develop better and
faster nanofabrication techniques. Furthermore, our curiosity as to how life
works, and how it can be improved from a medical perspective, stands to gain a
great deal from advances in nanotechnology. Novel nanofabrication techniques are
opening up the possibilities for mimicking the inherently nano-world of the cell,
i.e., the nanotopographies of the extracellular matrix (ECM) and the
nanochemistry presented on both the cell membrane and the ECM. In addition,
biosensing applications that rely on fabrication of high-density, precision
arrays, e.g., DNA or gene chips and protein arrays, will gain significantly in
efficiency and, thus, in usefulness once it becomes possible to fabricate
heterogeneous nanoarrays. Clearly, continued advances in nanotechnology are
desired and required for advances in biotechnology. In this review, we describe
the leading techniques for generating nanopatterns with biological function
including parallel techniques such as extreme ultraviolet interference
lithography (EUV-IL), soft-lithographic techniques (e.g., replica molding (RM)
and microcontact printing (muCP)), nanoimprint lithography (NIL), nanosphere
lithography (NSL) (e.g., colloid lithography or colloidal block-copolymer micelle
lithography) and the nanostencil technique, in addition to direct-writing
techniques including e-beam lithography (EBL), focused ion-beam lithography
(FIBL) and dip-pen nanolithography (DPN). Details on how the patterns are
generated, how biological function is imparted to the nanopatterns, and examples
of how these surfaces can and are being used for biological applications will be
presented. This review further illustrates the rapid pace by which advances are
being made in the field of nanobiotechnology, owing to an increasing number of
research endeavors, for an ever increasing number of applications.
PMID- 17037833
TI - The analytical approach to polydimethylsiloxane microfluidic technology and its
biological applications.
AB - This review article discusses PDMS (polydimethylsiloxane) microfluidic devices
and their biological applications. First, the already developed devices are
classified from the viewpoints of underlying technology within a common logical
framework comprising single-layer, multilayer, and integrated devices, as well as
surface chemistry modifications of PDMS. Combinatorial techniques are applied to
re-derive existing devices within this framework. Next, the relevant scales of
both microfluidics and biology are compared, obtaining the promise and
limitations of PDMS microfluidics. Finally, the body of work is reclassified in
terms of addressed biological applications and compared to the standard methods
in cellular and molecular biology, to offer insights for future devices and
applications.
PMID- 17037834
TI - Immobilization of biomaterials to nano-assembled films (self-assembled
monolayers, Langmuir-Blodgett films, and layer-by-layer assemblies) and their
related functions.
AB - For utilization of highly sophisticated functions of biomaterials in nano-scale
functional systems, immobilization of biomaterials on artificial devices such as
electrodes via thin film technology is one of the most powerful strategies. In
this review, we focus on three major organic ultrathin films, self-assembled
monolayers (SAM), Langmuir-Blodgett (LB) films, and layer-by-layer (LBL)
assemblies, and from the viewpoints of biomaterial immobilization, typical
examples and recent progresses in these film technologies are described. The SAM
method allows facile contact between biomaterials and man-made devices, and well
used for bio-related sensors. In addition, recent micro-fabrication techniques
such as micro-contact printing and dip-pen nanolithography were successfully
applied to preparation of biomaterial patterning. A monolayer at the air-water
interface, which is a unit structure of LB films, provides a unique environment
for recognition of aqueous biomaterials. Recognition and immobilization of
various biomaterials including nucleotides, nucleic acid bases, amino acids,
sugars, and peptides were widely investigated. The LB film can be also used for
immobilization of enzymes in an ultrathin film on an electrode, resulting in
sensor application. The LBL assembling method is available for wide range of
biomaterials and provides great freedom in designs of layered structures. These
advantages are reflected in preparation of thin-film bio-reactors where multiple
kinds of enzymes sequentially operate. LBL assemblies were also utilized for
sensors and drug delivery systems. This kind of assembling structures can be
prepared on micro-size particle and very useful for preparation of hollow
capsules with biological functions.
PMID- 17037835
TI - The use of magnetic nanoparticles in the development of new molecular detection
systems.
AB - Magnetic nanoparticles have been widely used in biomolecular separation and
discrimination which coincidentally also represents the basis for most current
day molecular diagnostic procedures. The specificity, affinity, and binding
capacity of magnetic nanoparticles depends on their size, form, dispersion, and
surface chemistry. In this review, we will briefly analyze how these factors
affect biomolecular separations and focus on the use of magnetic nanoparticles in
monitoring the microbial biodiversity in the environment. We found that magnetic
nanoparticles are especially effective for biomolecular separations in
environmental samples collected and preserved with fixatives. This feature,
together with the high sample throughput capability and the generic low cost,
makes magnetic nanoparticles particularly suitable for environmental microbial
monitoring. Furthermore, key features that permit the optimization of magnetic
nanoparticles-based separations and that can be useful in the development of new
analytical procedures are also discussed.
PMID- 17037836
TI - Force measurements between emulsion droplets-ssDNA conjugates: a new tool for
medical diagnostics.
AB - We describe here a new system involving direct force measurements between
biomolecules that could be used in biomedical diagnostics. The method consists in
the use of magnetic emulsion droplets bearing immobilized single stranded DNA
fragments (ssDNA, Deoxyribo Nucleic Acid). The immobilized ssDNA fragments are
able to recognize complementary DNA molecules via specific hydrogen binding
(hybridization process). The ssDNA used in this study are 32 bases
oligonucleotides functionalized at their 5' extremity with biotin and then
immobilized onto the magnetic nanodroplets via interactions with streptavidin
previously chemically grafted onto the nanomagnetic support. The aim of this work
is to evaluate the possible detection of captured nucleic acid targets via single
force measurements as an alternative to classical ELOSA (Enzyme Linked Oligo
Sorbent Assay). The obtained results are discussed mainly in terms of
electrostatic interactions.
PMID- 17037837
TI - Self assembly of DNA nanoparticles with polycations for the delivery of genetic
materials into cells.
AB - Increasing attention has been paid to technology used for the delivery of genetic
materials into cells for gene therapy and the generation of genetically
engineered cells. So far, viral vectors have been mainly used because of their
inherently high transfection efficiency of gene. However, there are some problems
to be resolved for the clinical applications, such as the pathogenicity and
immunogenicity of viral vectors themselves. Therefore, many research trials with
non-viral vectors have been performed to enhance their efficiency to a level
comparable to the viral vector. Two directions of these trials exist: Material
improvement of non-viral vectors and their combination with various external
physical stimuli. In this study gelatin was selected as a non-viral carrier for
DNA. To give a positive charge to gelatin, different extents introduction of
ethylenediamine (Ed), spermidine (Sd), and spermine (Sm) were reacted with
gelatin in the presence of a water-soluble carbodiimide. When positively charged
gelatin derivatives (Ed, Sd, and Sm) were mixed with negatively charged DNA, a
self assembly of DNA nanoparticle (complex) was formed within few minutes through
electrostatic interaction. Irrespective of the type of gelatin derivatives, the
apparent molecular size of DNA was reduced by increasing the gelatin/DNA mixing
ratio to attain a saturated value of about 150 nm. The condensed gelatin/DNA
complexes showed the zeta potential of 10-15 mV. The amount of DNA internalized
into the cells was significantly increased by the complexation with every gelatin
derivative. The cells incubated with the gelatin/DNA complexes exhibited
significantly stronger luciferase activities than naked plasmid DNA. This study
clearly demonstrates and self-assembled DNA complexes has potential as a gene
delivery vechile and are stable to transfer genetic materials to cells.
PMID- 17037838
TI - From hollow shells to artificial cells: biointerface engineering on
polyelectrolyte capsules.
AB - Biomimetic composites can be fabricated by coating hollow polyelectrolyte
capsules with biological interfaces such as a phospholipid membrane and proteins.
Polyelectrolyte capsules have been templated applying the Layer-by-Layer
technique of polyelectrolyte assembled on decomposable cores, which are destroyed
after the assembly of the polyelectrolyte multilayer. Phospholipid vesicles of
200-300 nm size are spreaded on the capsule wall forming a continuous lipid
membrane. Further functionalisation of the outer capsule wall can be achieved
with fused virions and recrystallised S-layers. Compartimentation of the capsule
interior with lipid vesicles has been possible by using a solvent exchange
method. The functionalisation of the outer capsule surface with biomolecules,
together with the creation of internal compartments in the capsule, open new
nanobiotechnological challenges towards the fabrication of artificial cells.
PMID- 17037839
TI - Stable photoinduced charge separation in nanostructured films containing a
1,4,5,8-naphthalenetetracarboxylic diimide and cytochrome c.
AB - Photoinduced electron transfer between 1,4,5,8-naphthalenetetracarboxylic
diimides (NDI) and the redox protein cytochrome c (cyt c) was studied in solution
and in spin-coated thin films. The NDI derivatives employed in this study were
N,N'-bis(butyl)-1,4,5,8-naphthalenetetracarboxylic diimide (BNDI) and N,N'-bis(2
phosphonoethyl)-1,4,5,8-naphthalenetetracarboxylic diimide (PNDI). Irradiation of
the NDI in solution with UV light (365 nm), in the presence of cyt c, resulted in
the reduction of the heme iron from the Fe3+ to the Fe2+ state. When PNDI and cyt
c were co-deposited by spin-coating on quartz, glass, and silicon substrates,
photoactive films were obtained. Exposition of the films to a UV lamp or natural
sun light resulted in photoreduction of the protein, generating a stable charge
separated state. Thin films containing segregated layers of BNDI and cyt c were
also prepared. Irradiation of these films, however, resulted in protein
degradation. The results can be explained through the formation of imide
radicals, which transfer an electron to cyt c in the co-deposited films. In the
case of segregated films, protein photodegradation suggests the formation of
singlet oxygen within the films.
PMID- 17037841
TI - Investigation of sisal fibers by atomic force microscopy: morphological and
adhesive characteristics.
AB - Atomic force microscopy (AFM) was used to study the nanoscale surface chemistry
and morphological changes caused by chemical treatment of sisal fibers. Scanning
Electron Microscopy (SEM) micrographs indicated that sisal in natura (bundle of
fibers) is formed by fibers with diameters of approximately 10 microm. AFM images
showed that these fibers consist of microfibrils with diameters varying from 250
to 600 nm, which are made up of nanofibrils of ca. 20 nm in diameter. The
adhesion force (pull-off force) between the AFM tip and the fibers surface
increased after benzylation, pointing to a decrease in the polar groups on the
sisal fiber. The adhesion map measured over a scan range of 3 microm was
heterogeneous in samples treated with 40% NaOH and the low adhesion sites
disappeared after benzylation. Using an established mathematical model, it was
possible to evaluate the increase in adhesion work and consequently in the
interaction between the AFM tip and sisal fibers. These results indicated that
AFM can detect heterogeneity in the wettability of sisal fibers with nanometer
resolution and can be applied in the study of fiber-matrix adhesion in polymer
composites.
PMID- 17037840
TI - Galactose derivative immobilized glow discharge processed polyethersulfone
membranes maintain the liver cell metabolic activity.
AB - New strategies aimed to surface modification of polymeric membranes are crucial
to optimise cell-biomaterial interactions in vivo and in vitro biohybrid systems.
In this paper, we investigated the surface modification of Polyethersulfone (PES)
membranes by plasma polymerisation of acrylic acid monomers (PES-pdAA) and by
immobilization of galactonic acid through a hydrophilic "spacer arm" molecule
(PES-pdAA-SA-GAL). The modification steps were characterised by high resolution X
ray photoelectron spectroscopy. The performance of modified and unmodified
membranes was evaluated by assessing the expression of liver specific
biotransformation functions of pig and human hepatocytes. Human liver cells
cultured on PES-pdAA-SA-GAL membranes displayed an enhanced albumin production,
urea synthesis and protein secretion for 24 days of culture. The immobilisation
of galactose derivative units on the membrane allowed specific interactions with
hepatocytes biomimicking the cellular microenvironment and produced an
improvement of the long-term maintenance and differentiation of human
hepatocytes.
PMID- 17037842
TI - Immobilization of methylene blue on self-assembled iodine monolayers on gold.
AB - The immobilization of methylene blue (MB) on iodine-covered Au(111) is studied by
electrochemical techniques, scanning tunneling microscopy (STM), Auger Electron
Spectroscopy (AES), and Raman spectroscopy. Results show that MB species are
efficiently adsorbed on the square root of 3 x square root of 3 R30 degrees I
lattice on Au(111). The electrochemical behavior of the adsorbed MB molecules is
reversible, indicating a relatively fast electron transfer from the Au(111)
surface to the immobilized MB species through the iodine layer. STM images with
molecular resolution are consistent with adsorption of MB dimers on a square root
of 3 x square root of 3 R30 degrees I lattice placed atop of the Au(111)
substrate. Results are compared to those obtained for MB immobilized on Au(111)
covered by S(n) (n = 3-8) surface structures.
PMID- 17037843
TI - Analysis of extracellular matrix production in artificial cartilage constructs by
histology, immunocytochemistry, mass spectrometry, and NMR spectroscopy.
AB - Artificial cartilage constructs based on primary porcine chondrocytes embedded in
agarose gel were cultivated for six weeks under static, free swelling conditions.
Standard biochemical assays, immunocytochemical staining methods, MALDI-TOF mass
spectrometry, and non-invasive 13C solid-state NMR spectroscopy were used to
assess cell proliferation, chondrocyte metabolism, extracellular matrix
composition, matrix production, and the nanoarchitecture of the macromolecules in
the constructs. In particular the production of sulphated glycosaminoglycans such
as chondroitin sulphate was investigated quantitatively. Standard methods such as
histological and immunocytochemical tools as well as spectrophotometric assays
indicated the production of extracellular matrix in the artificial cartilage
constructs. In addition, MALDI-TOF mass spectrometric data allowed to clearly
identify the production of chondroitin sulphate in the tissue engineered
cartilage. While all these methods require invasive sample treatment, 13C NMR
spectroscopy allows to study the composition of the artificial cartilage
constructs without previous manipulations. Though lower in sensitivity, 13C NMR
spectra clearly showed the presence of chondroitin sulphate in the constructs. To
increase the sensitivity of the NMR method, a culture medium that contained
uniformly 13C labelled glucose but no sodium pyruvate or L-glutamine was used.
Thus, further insights into the chondrocyte metabolism ex vivo are possible.
Therefore, MALDI-TOF mass spectrometry and 13C solid-state NMR are useful
experimental techniques that can assist the quantitative evaluation and quality
control of artificially engineered tissues.
PMID- 17037844
TI - Controlled DNA-templated metal deposition: towards ultra-thin nanowires.
AB - In this paper, we report the metallization of a dsDNA template using a novel
photography-derived two-step strategy in which dsDNA is first complexed with
Ag(I) ions and then irradiated with UV light at 254 nm. The nucleobases act as
light harvesters and sensitizers, triggering the photoreduction of the complexed
silver ions. This process yields a silver nanoparticles blueprint along the DNA
strand. The silver latent image is then developed by depositing metallic nickel
through an electroless plating process. This photography-derived procedure
generates very homogeneous and evenly distributed strings of silver-core/nickel
shell nanoparticles. Although still discontinuous, we believe that such chains
can serve as the base for obtaining continuous metal nanowires. Furthermore, this
process can most likely be extended to other plating metals, resulting in a
broadly general procedure for metallizing DNA with a variety of different
materials. Because of the intrinsic simplicity in using light as the key step,
this methodology might be amenable to large-scale development, eventually leading
to a very efficient molecular-photolithography process.
PMID- 17037845
TI - Entropic interactions in soft nanomaterials.
AB - We review the forces that rule interactions between phospholipid membranes and
other soft nanomaterials such as polymers and colloids. Contrary to traditional
nanostructures, soft materials display a high susceptibility to the fluctuations
of the thermal environment, leading to new forces of an essentially entropic
nature.
PMID- 17037846
TI - Development of an amperometric ethanol biosensor based on a multiwalled carbon
nanotube-Nafion-alcohol dehydrogenase nanobiocomposite.
AB - An amperometric biosensor for the determination of ethanol has been constructed.
It comprises a multiwalled carbon nanotubes (MWNTs) conduit, a Nafion binder, and
an alcohol dehydrogenase (ADH) function. The measurement of ethanol is based on
the signal produced by beta-nicotinamide adenine dinucleotide (NADH), the product
of the enzymatic reaction. The MWNTs are cylindrical with an outer diameter in
the range 40-60 nm, an inner diameter in the range 2-5 nm, and a length of up to
several micrometers. The homogeneity of the resulting nanobiocomposite film was
characterized by field emission scanning electron microscopy (FESEM) and atomic
force microscopy (AFM). The performance of the MWNTs-Nafion-ADH nanobiocomposite
modified glassy carbon electrode was examined using cyclic voltammetry and
amperometry in presence of NADH and in the presence of ethanol. The
electrocatalytic activity of MWNTs towards the oxidation of NADH has allowed an
effective low-potential amperometric determination of ethanol. In the case of 6
mgmL(-1) ADH, the MWNTs-Nafion-ADH nanobiocomposite film displayed a sensitivity
of 830 nAmM(-1), a linear range up to 0.1 mM, a detection limit of 3 microM, and
a response time of about 4 s.
PMID- 17037847
TI - Poly-lactide-co-glycolide microparticle sizes: a rational factorial design and
surface response analysis.
AB - Microsphere size is a primary determinant of solute release velocity. We present
here a rational way for producing PLGA microspheres with different and controlled
sizes. The following process variables were studied: Stirring velocity during the
second emulsion step, dispersed and continuous phases volume ratio, and
poly(vinyl alcohol) concentration in the continuous phase. A full factorial
experimental design 2(3) with triplicate at the central point was used to
determine the influence of variables on PLGA microsphere mean size. The stirring
velocity and poly(vinyl alcohol) concentration were the main variables at 0.95
significance level. An influence of PVA and stirring velocity on microspheres
size is observed, there is no correlation for DP/CP volume ratio on size of
microspheres. By combining the two variables--the stirring velocity and
poly(vinyl alcohol) concentration, the surface response was analyzed. The
increase of poly(vinyl alcohol) concentration with concomitant increase on
stirring velocity produced microspheres with the lower sized. In contrast the
lower poly(vinyl alcohol) concentration and the lower stirring velocity used
produced the higher microspheres sized. Uniformly spherical and smooth
microspheres (4-15 microm of diameter) were obtained. No significant difference
was observed on Ponca S loading within the experimental region. Our results open
the possibility of formulating PLGA microspheres with custom sizes performing a
minimum of experiments as required for specific applications.
PMID- 17037848
TI - Poly(amino acid)-facilitated electrochemical growth of metal nanoparticles.
AB - Poly(amino acids) are natural chelating agents for various metal ions. Zinc ions
were encapsulated in situ in a conductive polypyrrole film using polyglutamic
acid as a localized complexing agent within the film. The subsequent
electrochemical reduction of the metal ions to zero-valent metal leads to the
formation of the nanoparticles. The electrochemical approach demonstrated in this
report provides facile regeneration of the particles and also prevents
aggregation of nanoparticles in the conductive polymeric film. The correlation of
the amount of zinc with the thickness of the film indicates that the zinc resides
largely in the outer layer of the film. TEM and EDS data show that the
nanoparticles formed are composed of zinc and are 18 +/- 7 nm in diameter. The
nanoparticle/ polymer composite was used to reduce halogenated organics,
indicating its potential usefulness in remediation applications.
PMID- 17037849
TI - Cell toxicity studies of albumin-based nanosized magnetic beads.
AB - The aim of this study was to prepare bovine serum albumin-based beads containing
maghemite nanoparticles incorporated via ionic magnetic fluid and to evaluate the
cell toxicity of this biocompatible system using the J774-A1 cell line.
Transmission electron micrographs obtained from the magnetic fluid sample were
used to estimate the average particle diameter around 7.6 nm and diameter
dispersion of 0.22. The BSA-based magnetic beads were prepared using the heat
protein denaturation route. The nanoparticle concentration in the magnetic fluid
sample used for the synthesis of the magnetic beads was in the range of 1.2 x
10(16) to 2.3 x 10(17) particle/ml. The methodology used to investigate the cell
toxicity of the magnetic beads was the classical MTT assay. Our observation
showed that the toxicity against the J774-A1 cell line depends upon the amount of
magnetic material incorporated into the magnetic nanobeads and was found to be
14, 11, 9, 5, and 3% for 2.3 x 10(17), 1.2 x 10(17), 4.6 x 10(16), 2.3 x 10(16),
and 1.2 x 10(16) particle/ml, respectively.
PMID- 17037850
TI - The influence of urea on the structure of proteins in reversed micelles.
AB - Static fluorescence measurements from the protein Tryptophan (Trp) residues and
circular dichroism (CD) spectroscopy were used to investigate changes on the
tertiary and secondary structures of the protein bovine serum albumin (BSA) and
the dimeric enzyme hexokinase (HK) type PII from yeast, entrapped in reversed
micelles (RMs). The latter were obtained from the amphiphilic AOT (sodium bis-2
ethylhexyl sulfosuccinate) in n-hexane, at several water to surfactant ratios, W.
BSA and HK were found to be anchored at the RM interface in close contact with
the surfactant layer, regardless of the size of the waterpool. For BSA, such
interaction promotes partial protein unfolding, according to CD data that showed
a decrease in the content of helical structure from 66% in a buffer solution to
48% in the micellar moiety. When urea was present in the micelle, further loss in
helical structure occurred, thus indicating that the combined effect (micellar
environment and urea) altered the BSA conformation to a greater extent than did
RM or urea alone. Interestingly, Trps probed the same environment in the micelle,
regardless of the presence of urea, but the fluorescence was quenched to a higher
extent with urea. Thus, the fluorofore emission must have been affected either by
the direct interaction of urea or by indirect exchange of water structure caused
by urea interacting with water and the micellar interface. Both mechanisms might
be of relevance in the solvation properties nearby the Trps. For HK, an
association between the enzyme and the micelle interface was indicated in the CD
spectra, which exhibited a randomized structure upon interaction, whatever the RM
droplet size. The urea addition to the micelle water pool did not cause further
impact on the HK conformation. In addition, the influence of urea at the RM
interface was not sensed by the exposed tryptophans of the enzyme, unlike the
results for BSA.
PMID- 17037851
TI - Structural evaluation of phospholipidic nanovesicles containing small amounts of
chitosan.
AB - In this study we present a full characterization of nanovesicles containing
soybean phosphatidylcholine and polysaccharide chitosan. The nanovesicles were
prepared by the reverse phase evaporation method, including the preparation of
reverse micelles followed by the formation of an organogel, which is dispersed in
water to yield the final liposomal particles. Structural changes as a function of
the chitosan amount and the filter porosity used in the nanovesicles preparation
were studied employing Static and Dynamic Light Scattering as well as Small Angle
X-ray Scattering. The hydrodynamic radius of the nanovesicles ranged between 106
and 287 nm, depending on the chitosan contents and the filter porosity. A
comparison with nanovesicles free of chitosan indicates the existence of higher
contents of multilamellar structures that depends on the chitosan concentration
in the vesicles containing chitosan. Typical spherical vesicles having nanometric
diameters with polydispersity mostly desired in the biomedical area could only be
achieved by filtration through a 0.45 microm porous filter.
PMID- 17037852
TI - Zinc phthalocyanine/magnetic fluid complex: a promising dual nanostructured
system for cancer treatment.
AB - In this study we evaluated the photophysical, photochemical properties of the
zinc phthalocyanine/ magnetic fluid (ZnPC/MF) complex in liposomal medium. As a
result of the present investigation we propose the liposome-encapsulated ZnPC/MF
complex as a very promising nanostructured device for cancer treatment. The
spectroscopy characterization and the in vitro dark toxicity of both ZnPC and
ZnPC/MF complex in Hank's and in liposomal medium are reported. Our findings
revealed that the spectroscopic properties of the ZnPC associated or not with MF
presented little differences and are very close to what one expects from an ideal
photosensitizer compound. Indeed, the ZnPC/MF complex in liposomal medium
presented lower dark toxicity compared to the ZnPC/MF complex in Hank's, strongly
supporting the use of the former for cancer treatment.
PMID- 17037853
TI - Wet powder processing of sol-gel derived mesoporous silica-hydroxyapatite hybrid
powders.
AB - This paper describes a method by which a porous silica coating layer can be
obtained on different apatite particles through a simple sol-gel synthesis route.
Sol-gel derived powders of hydroxyapatite (HAP) and beta tricalciumphosphate
(beta-TCP) were coated with a mesoporous silica using C16TAB
(hexadecyltrimethylammonium bromide) as a template in order to induce mesophase
formation. Further calcination of the material removes the template from the
mesophase and leaves a highly ordered hexagonal arranged mesoporous silica
structure with a core of HAP/beta-TCP. The phase purity of the SiO2/apatite
composites has been thoroughly investigated by the means of FT-IR, XRD, and solid
state 31P MAS NMR. The phase purity of these materials is shown to be dependent
on the solubility properties of the used apatites. The hybrid materials are
suitable as a multifunctional biomaterial where osteoconductive properties can be
combined with drug delivery.
PMID- 17037854
TI - Charge patterns as templates for the assembly of layered biomolecular structures.
AB - Electric fields are used to guide the assembly of biomolecules in predefined
geometric patterns on solid substrates. Local surface charges serve as templates
to selectively position proteins on thin-film polymeric electret layers, thereby
creating a basis for site-directed layered assembly of biomolecular structures.
Charge patterns are created using the lithographic capabilities of an atomic
force microscope, namely by applying voltage pulses between a conductive tip and
the sample. Samples consist of a poly(methyl methacrylate) layer on a p-doped
silicon support. Subsequently, the sample is developed in a water-in-oil
emulsion, consisting of a dispersed aqueous phase containing biotin-modified
immunoglobulinG molecules, and a continuous nonpolar, insulating oil phase. The
electrostatic fields cause a net force of (di)electrophoretic nature on the
droplet, thereby guiding the proteins to the predefined locations. Due to the
functionalization of the immunoglobulinG molecules with biotin-groups, these
patterns can now be used to initiate the localized layer-by-layer assembly of
biomolecules based on the avidin-biotin mechanism. By binding 40 nm sized biotin
labelled beads to the predefined locations via a streptavidin linker, we verify
the functionality of the previously deposited immunoglobulinG-biotin. All
assembly steps following the initial deposition of the immunoglobulinG from
emulsion can conveniently be conducted in aqueous solutions. Results show that
pattern definition is maintained after immersion into aqueous solution.
PMID- 17037855
TI - An engineered virus as a bright fluorescent tag and scaffold for cargo proteins-
capture and transport by gliding microtubules.
AB - We have demonstrated substantial capture and transport of fluorescently-labeled
engineered cowpea mosaic virus (CPMV) using Drosophila kinesin-driven
microtubules (MTs). The capture occurred through both NeutrAvidin (NA)-biotin and
antibody (IgG)-antigen interactions. The MTs were derivatized with rabbit anti
chicken IgG or biotin, and the virus was conjugated with chicken IgG or NA. The
CPMV conjugate was introduced into standard MT motility assays via convective
flow at concentrations as high as 1.36 nM, and became bound to the MTs in
densities as high as one virus per microm of MT length. When the CPMV conjugate
was present at 17 pM, the average speed of the MTs bearing the NA-virus was 0.59
+/- 0.08 microm/sec, and that of those bearing IgG-virus was 0.52 +/- 0.15
microm/sec. These speeds are comparable to those of the unladen MTs (0.61 +/-
0.09 microm/sec), the presence of the virus on the MT causing only a small
decrease in MT gliding speeds. The fluorescent CPMV appears to be superior to
fluorescent polystyrene spheres of the same size, as both a reporter tag and a
scaffold for MT-transported cargo proteins, because of its negligible non
specific adsorption and superior brightness. This work is important for the
development of sensors based on nanolocomotion and biological recognition, or new
strategies for the nanoassembly of biological structures.
PMID- 17037856
TI - Determination of the size of water-soluble nanoparticles and quantum dots by
field-flow fractionation.
AB - Field flow fractionation (FFF) technique is used to determine the size of water
soluble Au, ZnS, ZnS-Mn2+ nanoparticles, and CdSe, CdSe-DNA quantum dots (QDs).
The results of the FFF measurements are compared with the particle size analysis
using conventional techniques like scanning electron microscopy (SEM),
transmission electron microscopy (TEM), and dynamic light scattering (DLS)
studies. Water-soluble gold nanoparticles (AuNPs) stabilized by mercaptosuccinic
acid (MSA) as the ligand when analyzed by the SEM and DLS showed evidence of
extensive aggregation, preventing an accurate determination of the average
particle size. The TEM analyses without staining offered a facile measurement of
the nanoparticle core but average particle size determination required analysis
of the TEM image using image analysis software. On the other hand the FFF is
seemingly a convenient and easy method for the determination of the average
particle size of the AuNPs. In case of the ZnS and ZnS-Mn2+ nanoparticles with
mercaptopropionic acid (MPA) as the capping agent severe aggregation prevented
accurate estimation of particle sizes even by the high resolution TEM (HRTEM),
where as the size determination by the FFF was very facile. Analysis of the CdSe
DNA conjugate by the TEM was difficult as the sample got damaged upon exposure to
the electron beam. The FFF cross-flow condition is apparently noninvasive and
hence the technique was very effective in characterizing the CdSe-DNA QDs.
Furthermore, using this simple technique it was possible to fractionate a sample
of the AuNPs. The FFF measurement of water-soluble nanoparticles is an excellent
complement to characterization of such particles by the conventional tools.
PMID- 17037857
TI - Fabrication of nickel nanocontacts using nanostencils and electron beam assisted
SiO2 deposition.
AB - Nickel nanocontacts for studying ballistic magnetoresistance have been fabricated
by sputtering through FIB prepared nanostencil masks and by using electron beam
assisted deposition of SiO2 to reduce the size of FIB milled pores through
silicon nitride membranes. These two methods are discussed in terms of the
nanocontact sizes, fabrication, and yield. The smallest size of the nanocontacts
prepared using the nanostencil method was 40 nm and by the filling method was 1-2
nm. The maximum magnetoresistance measured was 1% and no evidence of a large
ballistic magnetoresistance was observed.
PMID- 17037858
TI - Measurement of light wavelength based on nanostructured ordered pore arrays.
AB - A new method of light wavelength measurement is presented based on the
nanostructured ordered pore arrays with multi-domains and centimeter square size
formed by solution dipping-colloidal monolayer. Because of periodicity of the
ordered pore arrays, perpendicular incidence of a parallel beam light on the
array will lead to the diffraction spots or ring, depending on relative sizes of
the beam and the domain in the arrays. The diffraction angle corresponds to
wavelength of the incident light. On this basis, one can measure the wavelength
of an incident light in transmission mode using such nanostructured ordered pore
arrays, which is different from the conventional one fabricated from Michelson
interference principle. Both the resolution and measurement precision can reach <
1 nm in such a simple method. Comparatively, this new measurement setup is simple
in structure, low in cost, convenient in measurement, and especially, small in
size. It could be used for online demarcation and real-time measurement of light
wavelength in such as, mine operation, seabed exploration, and even space
exploration due to its miniature.
PMID- 17037859
TI - Polymer-coated magnetic nanoparticles: surface modification and end
functionalization.
AB - ATRP (atom transfer radical polymerization) approach was employed to synthesis
polymer-coated magnetite nanoparticles. These particles had an average diameter
of 7.1 nm and a narrow size distribution. Characterization was performed using
various techniques like Transmission Electron Microscopy (TEM), Ultraviolet
Visible spectroscopy (UV-vis), Fourier Transform Infrared spectroscopy (FTIR),
Atomic Force Microscopy (AFM), and Vibrating Sample Magnetometry (VSM). The
challenge was to obtain a thin shell and discrete particles in an unagglomerated
state. Several factors like presence/choice of solvent, monomer-to-initiator
concentration and structure of initiator were found to play a key role in this
study. Attempts have been made to tailor the polymer shells by end
functionalization. This work has an enormous biomedical application potential.
PMID- 17037860
TI - Preparation of Mg-vermiculite nanoparticles using potassium persulfate treatment.
AB - Delamination/exfoliation process of the Mg-vermiculite (Letovice, Czech
Republic), particles with size less than 5 microm, was studied after potassium
persulfate treatment and compared with known method utilized hydrogen peroxide
treatment. X-ray powder diffraction (XRPD) patterns showed that treatment of Mg
vermiculite with different molar concentration of potassium persulfate: c = 0.02,
0.04, and 0.08 mol x dm(-3) at the temperature 60 degrees C for 2 hr caused
reduction of relative intensity (I(rel.)) of the basal 001 diffraction to the
15%, 9%, and 4%, respectively, compared to intensity of 001 diffraction of
untreated Mg-vermiculite (I(rel.) = 100%). On the other hand I(rel.) of the 001
diffraction of Mg-vermiculite after treatment with 30% and 50% (c = 9.8 and 17.4
mol x dm(-3)) hydrogen peroxide at the 60 degrees C for 2 hr decreased only to
I(rel.) = 36% and 32%, respectively. Atomic Force Microscopy (AFM) and Scanning
Electron Microscopy (SEM) verified effect of potassium persulfate treatment on
structure degradation which is connected with higher degree of
delamination/exfoliation of the particles and their cracking into nano-sized
particles.
PMID- 17037861
TI - Mechanical property of lipid-coated polyelectrolyte microcapsules.
AB - The deformations of lipid coated polyelectrolyte capsules induced by osmotic
pressure were determined in poly(styrene sulfonate, sodium salt) (PSS) solution
by making use of the fact that PSS molecules with a molecular weight 70000 will
not penetrate into the capsules. At a critical osmotic pressure the initial
spherical capsules changed their shape and became an invagination. The
measurements of single particle light scattering provided the wall thickness of
the lipid-coated capsules with 25.6 nm while the thickness for pure
polyelectrolyte capsules in solution is about 21.6 nm, indicating that the
coating lipid layer has about 4 nm thickness. It demonstrates that DMPA forms a
bilayer on the surface of polyelectrolyte capsules. With these data, that the
elasticity coefficient of the lipid-coated capsules is about 426 Mpa can be
obtained.
PMID- 17037862
TI - Self-organized monolayer formation from binary mixtures of substituted alkyl
chains studied by STM.
AB - The molecular assembly of p-iodo-phenyl octadecyl ether (I-POE), p-iodo-phenyl
docosyl ether (I-PDE) and a binary mixture of these two molecules on graphite has
been studied using a scanning tunneling microscope. Each molecular system self
assembles on the graphite surface to form a stable monolayer. For the binary
system, the I-POE and I-PDE molecules do not mix on the surface, preferring
instead to form isolated monolayer domains. Here, the I-POE molecules are
preferentially adsorbed on the graphite surface, due to the effects of alkyl
chain length and the functional group on the monolayer structure.
PMID- 17037863
TI - Visible light active photocatalytic degradation of bisphenol-A using nitrogen
doped TiO2.
AB - Nitrogen doped titania was prepared by low temperature sol-gel method using
titanium precursor and nitrogen containing bases like triethylamine and
tetramethyl ammonium hydroxide compounds. The materials were characterized by
XRD, BET, SEM, XPS, DRS-UV, and FT-IR techniques. DRS-UV study substantially
indicates shift of the absorption edge of TiO2 to lower energy region. The phase
composition, crystallinity, specific surface area, and visible light activity of
nitrogen doped titania depend upon the preparation conditions. Photocatalytic
degradation of bisphenol-A in aqueous medium was investigated by TiO2 and
nitrogen doped TiO2 under visible light irradiation in a batch photocatalytic
reactor. The results indicate higher visible light activity for nitrogen doped
TiO2 than commercial TiO2 (Degussa P25) for bisphenol-A degradation. The
influence of various parameters such as initial concentration of bisphenol-A,
catalyst loading and pH was examined for maximum degradation efficiency.
PMID- 17037864
TI - Chitosan-mediated synthesis of gold nanoparticles by UV photoactivation and their
characterization.
AB - Recent researches have largely been focused on chitosan, which is deacetylated
chitin, the most abundant natural polysaccharide after cellulose. In this paper,
we report the fabrication of gold nanoparticles (GNPs) by UV photoactivation in
the presence of biopolymeric chitosan and the tracing of the gold salt solution
aging. Detailed UV-visible spectroscopy study witnessed the evolution of the
surface plasmon resonance (SPR) adsorption during the GNP growth. The effect of
chitosan in aqueous solution for the GNP preparation was investigated in detail.
The results indicated the size and distribution of GNPs could be controlled over
by altering the concentration of chitosan, and the GNP growth during aging was a
chitosan-mediated autocatalytic process. Fourier transform infrared spectroscopy
(FTIR) showed the hydroxyl in molecular chitosan was oxidized to carbonyl groups
in the fabrication of GNPs after aging and nitrogen atoms are the main sites for
the complexation of chitosan with Au atoms. Our synthesis method in the present
way can be used to form self-assemble monolayers of GNPs and fabricate biosensors
based on surface plasmon resonance effect.
PMID- 17037865
TI - Synthesis of neodymium hydroxide nanotubes and nanorods by soft chemical process.
AB - A facile soft chemical approach using cetyltrimethylammonium bromide (CTAB) as
template is successfully designed for synthesis of neodymium hydroxide nanotubes.
These nanotubes have an average outer diameter around 20 nm, inner diameter
around 2 nm, and length ranging from 100 to 120 nm, high BET surface area of
495.71 m(2) g(-1). We also find that neodymium hydroxide nanorods would be
obtained when CTAB absented in reaction system. The Nd(OH)3 nanorods might act as
precursors that are converted into Nd2O3 nanorods through dehydration at 550
degrees C. The nanorods could exhibit upconversion emission characteristic under
excitation of 591 nm at room temperature.
PMID- 17037866
TI - Dispersion of single-walled carbon nanotubes in a non-polar polymer, poly(4
methyl-1-pentene).
AB - Poly(4-methyl-1-pentene), PMP, a high melting polymer composed of hydrogen and
carbon, has the potential to become an alternative to polyethylene (PE) as
shielding material against Galactic Cosmic Radiation (GCR). PMP exhibits higher
thermal stability than PE and is transparent in the UV/visible region of the
electromagnetic spectrum. Single walled carbon nanotubes (SWNTs) were pretreated
with a polar solvent, N, N-Dimethylformimide (DMF), and then dispersed in a
halogenated hydrocarbon, cyclohexyl chloride, which also dissolved the non polar
polymer, PMP. The composites were characterized via differential scanning
calorimetry (DSC), dynamic mechanical analysis (DMA), microhardness measurements,
and optical microscopy. DMA data revealed that the carbon nanotubes contributed
to the enhancement of the high temperature alpha(c) relaxation which is thought
to arise from motion around crystalline regions in the matrix. The storage
modulus (60 Hz) increased from 2409 MPa in the neat PMP to 3716 MPa at -50
degrees C. The magnitude of the increase diminished near and above the glass
transition region; the glassy matrix restricted motion of the crystalline
regions. DSC data showed an increase in the percent crystallinity of the
composite (75%) as compared to the neat polymer (68%). Low concentrations of
nanotubes, when well dispersed, produced nanocomposites with varying degrees of
transparency.
PMID- 17037867
TI - Combustion oxidization synthesis of unique cage-like nanotetrapod ZnO and its
optical property.
AB - Cage-like nano-tetrapod ZnO is a novel structure, which was successfully
synthesized by combustion oxidation at 850 degrees C. No catalyst or carrier
gases were used. Thorough SEM and TEM analyses revealed that the linking legs of
the tetrapod ZnO can have or not interface. The formation or not of an interface
is discussed and it was attributed to different growth process of the cage-like
ZnO nano-tetrapod. Enhanced UV emission peak at the wavelength of 375 nm,
featuring high intensity and narrow width, indicates a highly crystalline
structure. A green emission, recorded at 502 nm, was related to the defects of
the surface of the branching configuration as well as to the ZnO nuclei of the
cage-like nano-tetrapod ZnO.
PMID- 17037868
TI - Strong green luminescence of Mg-doped ZnO nanowires.
AB - The ZnO nanowires doped with Mg (Mg-ZnONWs) were produced by thermally oxidizing
Zn and Mg powders. TEM and XRD patterns indicated that Mg-ZnONWs were crystalline
with a wurzite structure. The Mg doping was confirmed with XPS measurements. The
green emission band at 500 nm in the photoluminescence spectrum of Mg-ZnONWs and
peaks at 366 nm in low intensity were observable. Raman spectrum indicated that
oxygen deficiency was not the dominant factor for the green emission. The green
emission was further directly observed with a digital camera.
PMID- 17037869
TI - Orthogonally-oriented nanotube arrays: theory.
AB - A novel surface involving ordered arrays of partially-embedded carbon nanotubes
is developed theoretically. Analysis indicates it should exhibit ultra-low values
for friction, adhesion and wear, and also possess superior thermal and electrical
properties. The surface consists of orthogonally-oriented, self-assembling arrays
of carbon nanotubes, partially embedded lengthwise in a solid substrate.
Calculations indicate that stiction forces due to van der Waals interactions can
be made small, perhaps more than an order of magnitude less than for Teflon and
other advanced perfluorocarbons. Static and kinetic frictional forces could be
three orders of magnitude less than for conventional solids.
PMID- 17037870
TI - Possible binding sites for biotin stabilized water soluble Ag nanoparticles: an
experimental and theoretical study.
AB - The evolution of Ag nanoparticles by photochemical reduction method and the
effect of biotin on their UV-Visible absorption spectrum were studied. Surface
modification studies were carried out on chemically reduced Ag nanoparticles. ATR
FTIR studies showed that the biotin molecules bind with the surface of Ag
nanoparticles through the oxygen of the carboxylate group. Theoretical
calculations were carried out on the structure of the biotin and the silver
complex of biotin (biotin(-)-Ag+) by optimizing their structures using density
functional calculations with the B3LYP method using the LANL2DZ basis set.
Theoretical calculations and experimental evidence favors a preferential binding
of biotin molecule to Ag nanoparticles through the carboxylate group.
PMID- 17037871
TI - Synthesis of nanocrystalline tin oxide thin film by swift heavy ion irradiation.
AB - Nanocrystals of tin oxide were formed in e-beam evaporated films by swift heavy
ion (SHI) irradiation. The nucleation of nanocrystals occurred due to electronic
excitation by swift heavy ion. Nanophase thin films are characterized
systematically by HRTEM, GAXRD, EDX, and UV/NIS absorption techniques.
Nanocrystals having size of 8 nm radius are synthesized in different substrates
during swift heavy ion irradiation and without subsequent annealing. SHI induced
nanocrystallization could be achieved in both crystalline and non-crystalline
substrates.
PMID- 17037872
TI - Triphenyl benzene-bridged fluorescent silsesquioxane: shape-controlled hybrid
silicas by hydrolytic conditions.
AB - A new silsesquioxane molecule was synthesized, in which triphenyl benzene was
connected with three Si(OC2H5)3 groups using three urea groups as the bridge. The
molecule could self-assemble through the intermolecular H-bonding among urea
groups and pi-pi interaction of triphenyl benzene core in the solution and it
could also be transferred into hybrid silicas by hydrolysis. When the non
preorganized silsesquioxane was hydrolyzed, isolated spherical hybrid silica was
gained. However, when the silsesquioxane was preorganized before the
hydrolyzation uniform interconnected spherical hybrid silica and intertwined
nanofibrous one could be generated under acidic and basic conditions,
respectively. The photoluminescence (PL) spectra of the obtained hybrid silicas
showed that they still kept the emission properties of their precursor
silsesquioxane, and the shift of the emission bands was due to the pi-pi
interaction of triphenyl benzene in the course of polycondensation.
PMID- 17037873
TI - Bicrystalline zinc oxide nanocombs.
AB - Bicrystalline ZnO nanocombs have been prepared by zinc powder evaporation at 650
degrees C. Structural analysis showed that as-synthesized samples are composed of
two crystals that form a twin structure parallel to the (113) plane with the
growth direction of the branching nanowires and the main stem closely parallel to
(0001) and (0110), respectively. Due to the unique twin structures, both sides of
the main stems could be Zn-terminated ZnO(0001) polar surfaces. The chemically
active surfaces make the aligned branching nanowires grow from both sides of the
main stems, which is consistent with the structure of the obtained bicrystalline
nanomaterials. The growth of bicrystalline ZnO nanocombs can be explained by
polar-surface dominated growth and twins induced growth mechanisms.
PMID- 17037874
TI - Preparation of conductive polypyrrole-palladium composite nanospheres by inverse
microemulsion polymerization.
AB - Conductive polypyrrole-palladium (PPy-Pd) composite nanospheres of about 50 nm in
diameter, containing dispersed Pd metal nanoparticles of about 2-4 nm in size,
were prepared in a 1-step oxidative polymerization of pyrrole by Pd(NO3)2.
Pyrrole was oxidized by Pd(NO3)2 in an inverse microemulsion polymerization
system, yielding PPy nanospheres and elemental Pd nanoparticles simultaneously.
Palladium nanoparticles were uniformly dispersed in the nanospheres of PPy
chains. The latter also exhibited an enhanced effective conjugation. The chemical
composition of the PPy-Pd composite nanospheres was characterized by X-ray
photoelectron spectroscopy and FTIR spectroscopy. The crystalline structure of
the Pd nanoparticles was deduced from X-ray diffraction patterns. The morphology
of the composites was revealed by scanning and transmission electron microscopy.
PMID- 17037875
TI - Influence of anions on the morphology of nanophase alpha-MnO2 crystal via
hydrothermal process.
AB - The alpha-MnO2 nanocrystal nanowires, nanoplates, and nanoflowers have been
successfully synthesized by a common hydrothermal treatment of different
solutions containing KMnO4 and NH4X (X = Cl-, Ac-, NO3-, SO4(2-), and PO4(3-)) at
140 degrees C for 24 h. The influence of anions on the morphology of final
product is discussed. According to our experimental results, we proposed a
possible mechanism of the formation of different morphologies of nano-phase alpha
MnO2 and considered that the growing process was due to the initial plate-like
MO(x) absorbing different anions and cooperation with them, which contributes to
the final morphology of the product.
PMID- 17037876
TI - Large-scale synthesis of a novel tri(8-hydroxyquioline) aluminum nanostructure.
AB - A novel tri(8-hydroxyquioline) aluminum (AlQ3) nanostructure was prepared on
large scale at low cost by low-temperature physical vapor deposition (PVD). The
morphologies, the chemical bondings, and photoluminescence of the AlQ3
nanostructure were investigated by environmental scanning electronic microscopy
(ESEM), Fourier transform infrared spectrum (FT-IR), and photoluminescence (PL)
spectra, respectively. The AlQ3 nanostructure was composed of micro-sphere with
nanowire-cluster growing on the surface. The diameter of micro-sphere and
nanowire were about 5 microm and 80 nm, respectively. FT-IR results indicated
that the AlQ3 molecule had a strong thermal stability under research conditions.
The growth mechanism of the novel nanostructure was discussed. The novel organic
nanostructure would be believed to attractive building field-emission devices and
other optical devices.
PMID- 17037877
TI - Sonochemical synthesis of CdS and CdSe nanowires.
AB - A convenient sonochemical route was developed to fabricate one-dimensional (1D)
CdS or CdSe assemblies via a simple template method with two-steps: Firstly, the
colloid one dimensional cadmium hydroxide particles were prepared as templates
under sonication; then, the colloid particles were converted into 1D CdS or CdSe
assemblies via a replacement reaction after the surface nucleation and crystal
growth processes. The as-prepared CdS and CdSe nanowires were characterized by
XRD, TEM, XPS, and UV-visible Spectroscopy. The effects of the ultrasonic
irradiation were discussed. It is believed that the ultrasound irradiation played
a positive role in both the assembly of the colloid cadmium hydroxide particles
into the 1D structure and the growth of CdSe and CdS nanowires. The effects of pH
on the morphologies of the cadmium hydroxide template were also discussed. The
band gaps of the as-prepared 1D CdSe and CdS assemblies were calculated to be 3.1
eV and 4.9 eV, respectively, indicating the quantum size effect. The as-prepared
products might have potential applications in nanodevices in future.
PMID- 17037878
TI - Synthesis of core-shell Au@polypyrrole nanocomposite using a dendrimer-template
approach.
AB - Conducting polymeric nanostructures have been reported recently, which were
produced from polypyrrole (PPy), including hollow nanocapsules, nanofibers,
nanoporous membranes, nanowires, and nanofilms. In most cases, new synthetic
routes were used aimed at controlling specific properties of these conducting
nanostructures at the molecular level. In this communication we present a new
chemical route to synthesize polypyrrole-based nanocomposites, in which
polyamidoamine (PAMAM) dendrimers encapsulating Au nanoparticles are used as
template. The two-step synthesis comprises the reduction of Au nanoparticles
inside PAMAM molecules followed by PPy polymerization around the PAMAM-Au
nanoparticles. The structure of the core-shell PAMAM-gold@polypyrrole nanospheres
comprises a 40 nm PPy shell enclosing a core of 3 nm gold nanoparticles, as
revealed by Transmission Electronic Microscopy (TEM). This new, environmentally
friendly approach may be suitable to produce hybrid nanomaterials for
applications in catalysis, batteries, sensors, and micro/nanoelectronic devices.
PMID- 17037879
TI - Scepticism greets plans to take politics out of the NHS.
PMID- 17037880
TI - At risk: the safety agency that failed to set the world on fire.
PMID- 17037881
TI - On voting for your healthcare.
PMID- 17037882
TI - Data briefing. Deficit forecasts, financial reality.
PMID- 17037883
TI - Mental health: same difference.
AB - There is widespread ignorance over services provided by the private and voluntary
sector. These can be cheaper and more flexible, and coming from niche market
tends to make them competitive. Opportunities for joint ventures with the NHS
appear more timely than ever and highlight the trend towards community-based
care, cohesion and co-operation.
PMID- 17037884
TI - On mental health.
PMID- 17037885
TI - The education and the digital revolution continues.
PMID- 17037886
TI - Dentinal hypersensitivity: a review.
AB - Tooth sensitivity is a very common clinical presentation which can cause
considerable concern for patients. This condition is frequently encountered by
periodontists, dentists, hygienists and dental therapists. The management of this
condition requires a good understanding of the complexity of the problem, as well
as the variety of treatments available. This review considers the aetiology,
incidence and management of dentinal hypersensitivity.
PMID- 17037887
TI - Prevalence and side preference for tooth grinding in twins.
AB - BACKGROUND: Estimates of the prevalence of tooth grinding in children range
considerably, reflecting different methods of recording. The main aims of this
study were to determine the prevalence of tooth grinding in monozygotic (MZ) and
dizygotic (DZ) twin pairs by assessing wear faceting on the primary canines, and
to compare the faceting on the right and left to determine whether children have
a side preference for grinding. METHODS: The sample consisted of 116 MZ twin
pairs and 124 dizygous DZ twin pairs, all participants in an ongoing study of
dento-facial development at the dental schools in Adelaide and Melbourne.
Evidence of wear faceting on primary maxillary and mandibular canine tips was
recorded from dental casts, and the side with the larger wear facet recorded.
Types of occlusal relationship, handedness, zygosity and gender were also
recorded, and associations between variables analysed statistically. RESULTS:
Canine tip wear facets were found in 100 per cent of the sample, and grinding was
lateralized in 59 per cent of children. MZ twin pairs showed a higher discordance
for grinding side preference than DZ twin pairs (33.8 per cent compared with 16.8
per cent), providing evidence of a mirror-imaging effect for grinding side
preference. There was no strong evidence that individuals had the same preference
for grinding side and handedness, although right-handers (RH) showed a preference
for a grinding side more often than non-right-handers (NRH) (63.6 per cent
compared with 51.2 per cent), consistent with previous findings that RHs display
more cerebral lateralization than NRHs. CONCLUSIONS: Tooth grinding appears to be
a universal phenomenon in children and is commonly expressed more on one side
than the other. The significantly higher discordance for grinding side preference
in MZ twin pairs compared with DZ twin pairs may reflect a mirror-imaging effect
in the former. However, at present we have no evidence to suggest that handedness
and preferred tooth grinding side are associated.
PMID- 17037888
TI - Maxillofacial trauma in major trauma patients.
AB - BACKGROUND: Trauma has been identified as a major public health problem in
Australia. Maxillofacial trauma constitutes a significant proportion of trauma,
although epidemiological studies in Australia are few. The purpose of this study
was to assess the prevalence and the epidemiological pattern of maxillofacial
trauma occurring in major trauma patients. METHODS: Data were obtained from the
Victorian State Trauma Registry, which included all major trauma patients in
Victoria. All data relating to maxillofacial trauma defined according to
Abbreviated Injury Scale and International Classification of Diseases codes from
1 July 2001 to 30 June 2004 were selected. Data collected included demographic
and injury details, and operative procedures carried out. RESULTS: Sixteen per
cent of major trauma patients sustained maxillofacial trauma. The highest
frequency of injuries occurred in the 15-24 years age group. More males were
affected than females (3:1). The majority of injuries were due to
transportrelated causes (69 per cent) and occurred mostly on roads, streets or
highways (70 per cent). Falls were the cause of 15 per cent of injuries, 10.5 per
cent of these injuries were fatal while 20.7 per cent needed rehabilitation. The
most common type of bony injury was a fractured maxilla. CONCLUSION: The need for
preventive strategies to be reinforced has been highlighted as transport-related
injuries remain high especially in the younger age groups.
PMID- 17037889
TI - Hospitalization of Western Australian children for oral health related
conditions: a 5-8 year follow-up.
AB - BACKGROUND: This study investigated in-patient oral health care provision for
children under 18 years of age in Western Australia. METHODS: Hospitalizations of
children for oral health conditions over a four-year period were analysed using
data obtained from the Western Australian Hospital Morbidity Data System (HMDS).
This study followed a previously published study examining similar data for 1995.
RESULTS: Between 1999-2000 and 2002-2003, a total of 26 497 episodes of care were
attributed to oral health conditions among children aged 0-17 years. The cost of
this care exceeded $40 million. Embedded and impacted teeth accounted for 33.2
per cent of oral health episodes, dental caries 28.3 per cent, pulp and
periapical tissue conditions 7.1 per cent and dentofacial anomalies 6.1 per cent.
With the exception of the infant age group (0-1 years), non-Aboriginal children
had higher admission rates than Aboriginal children. In the 13-17 year age group
a non-Aboriginal child was 31 times more likely to be admitted to hospital for an
oral condition than an Aboriginal child. CONCLUSIONS: This study confirms the
impact of oral health related conditions among children in Western Australia. It
is also clear that there are differences between age and population groups in
terms of access to in-patient dental services and exposure to risk factors for
specific oral conditions.
PMID- 17037891
TI - Fluoride content of still bottled water in Australia.
AB - BACKGROUND: Recently there has been a considerable increase in the consumption of
bottled water in Australia. Overseas studies have found the fluoride levels in
many bottled waters are well below levels considered optimal for preventing
dental caries. This raises the concern that if bottled water is regularly
consumed an effective means of preventing dental caries is unavailable. The aim
of this study was to determine the fluoride concentration in 10 popular brands of
still bottled water currently sold in Australia. METHODS: The fluoride content of
water samples were determined using an ion analyser and compared to a fluoride
standard. RESULTS: The fluoride concentration of all bottled waters was less than
0.08 ppm. Only three of the 10 brands indicated the fluoride content on their
labels. Melbourne reticulated water was found to be fluoridated at 1.02 ppm.
CONCLUSIONS: All bottled waters tested contained negligible fluoride which
justifies the concern that regular consumption of bottled water may reduce the
benefits gained from water fluoridation. It is recommended that all bottled water
companies should consider stating their fluoride content on their labels. This
will inform consumers and dental care providers of the levels of fluoride in
bottled water and allow an informed decision regarding consumption of fluoridated
versus non-fluoridated drinking water.
PMID- 17037890
TI - Ion uptake into demineralized dentine from glass ionomer cement following
pretreatment with silver fluoride and potassium iodide.
AB - BACKGROUND: Diamine silver fluoride (Ag(NH3)2F), referred to as AgF, has been
shown to provide a pronounced antimicrobial action against caries. The clinical
application of this material has been limited by the staining associated with
both teeth and tooth coloured restorative materials. The application of potassium
iodide (KI) after AgF eliminates stain formation. The purpose of this study was
to determine if a prior application of silver fluoride and potassium iodine to
demineralized dentine affected the uptake of strontium and fluoride from a glass
ionomer cement restoration. METHOD: Three cavities were prepared in each of five
recently extracted human third molars. The cavities were demineralized and
treated as follows. In each tooth, one cavity was left as a control, one cavity
was restored with glass ionomer cement and one cavity was treated with 1.8M AgF
and a saturated KI solution and then restored with glass ionomer cement. The
penetration of the various elements into demineralized dentine was measured by
their relative percentage weights using electron probe microanalysis (EPMA).
RESULTS: Fluoride uptake was significantly higher in the AgF and KI treated
samples compared to the other two samples and significantly higher in the glass
ionomer restored sample compared to the control. The application of AgF and KI
did not significantly interfere with the transfer of strontium from glass ionomer
cement into dentine. Silver and iodine deposits were present in the demineralized
dentine treated with AgF and KI. CONCLUSIONS: The application of AgF and KI onto
dentine prior to the placement of glass ionomer cement did not significantly
affect the strontium uptake into the subjacent demineralized dentine and the
fluoride levels in this zone were significantly increased.
PMID- 17037892
TI - Dissolution of porcine incisor pulps in sodium hypochlorite solutions of varying
compositions and concentrations.
AB - BACKGROUND: The solubility of dental pulp tissue in sodium hypochlorite has been
extensively investigated but results have been inconsistent; due most likely to
variations in experimental design, the volume and/or rate of replenishment of the
solutions used and the nature of the tissues assessed. Traditionally, the sodium
hypochlorite solutions used for endodontic irrigation in Australia have been
either Milton or commercial bleach, with Milton being the most common. Recently,
a range of Therapeutic Goods Administration (TGA) approved proprietary sodium
hypochlorite solutions, which contain surfactant, has become available. Some
domestic chlorine bleaches now also contain surfactants. The purpose of this
study was to perform new solubility assessments, comparing Milton with new TGA
approved products, Hypochlor 1% and Hypochlor 4% forte, and with a domestic
bleach containing surfactant (White King). METHODS: Ten randomly assigned pulp
samples of porcine dental pulp of approximately equal dimensions were immersed in
the above solutions, as well as representative concentrations of sodium
hydroxide. Time to complete dissolution was measured and assessed statistically.
RESULTS: White King 4% showed the shortest dissolution time, closely followed by
Hypochlor 4% forte. White King 1% and Hypochlor 1% each took around three times
as long to completely dissolve the samples of pulp as their respective 4%
concentrations, while Milton took nearly 10 times as long. The sodium hydroxide
solutions showed no noticeable dissolution of the pulp samples. CONCLUSIONS: The
composition and content of sodium hypochlorite solutions had a profound effect on
the ability of these solutions to dissolve pulp tissue in vitro. Greater
concentrations provided more rapid dissolution of tissue. One per cent solutions
with added surfactant and which contained higher concentrations of sodium
hydroxide were significantly more effective in dissolution of pulp tissue than
Milton.
PMID- 17037893
TI - Comparison of microshear bond strengths of four self-etching bonding systems to
enamel using two test methods.
AB - BACKGROUND: Recent advances in enamel and dentine adhesive technology have
resulted in the emergence of many new adhesive systems. Self-etching bonding
systems do not require a separate etching step and the newest systems are the
"all-in-one" systems which combine etching, priming and bonding into a single
application. This study reports laboratory enamel microshear bond strengths of a
self-etching priming and three all-in-one systems and also evaluates two
different microshear bond test methods. METHODS: One hundred and nineteen enamel
specimens were bonded (0.8 mm diameter) with either Clearfil Protect Bond
(Kuraray), Xeno III (Dentsply), G Bond (GC) or One-Up Bond F (Tokuyama) using
Palfique Estelite resin composite and stored in 37 degrees Celsius water for
seven days. The microshear bond test method used either a blade or wire to apply
the shear stress. Results were analysed with one-way ANOVA and post hoc (Tukey)
multiple comparison analysis. RESULTS: Clearfil Protect Bond demonstrated higher
and more consistent bond strengths than Xeno III, G Bond or One-Up Bond F. The
wire method showed much greater reliability in results, with a coefficient of
variation half that of the blade method. CONCLUSIONS: All-in-one adhesives seem
to be less reliable than the two-step self-etching priming adhesive when bonding
to enamel. Test method can significantly affect results in the microshear bond
test method.
PMID- 17037894
TI - Ex vivo evaluation of the ability of four different electronic apex locators to
determine the working length in teeth with various foramen diameters.
AB - BACKGROUND: The aim of this ex vivo study was to evaluate the accuracy of four
electronic apex locators (EALs) to determine the working length in teeth with
various foramen diameters. Our previous study revealed that electronically
measured canal length was influenced by the root canal diameter. It is not known
whether foramen size would interfere with the reading accuracy of an EAL.
METHODS: A total of 36 extracted human lower single rooted premolar teeth were
divided into four groups of nine teeth each. In groups A, B and C, the root
canals were instrumented using #10-80, #10-100 and #10-120 K-files, and the tip
of size #80, #100 and #120 K-files were permitted to pass through the apical
foramen to a length of 1mm, respectively. In group D, the teeth were instrumented
using #10-140 K-files and the tip of #140 K-file was permitted to pass through
the apical foramen to a length of 5 mm. Thus, the average apical foramen
diameters in groups A, B, C and D were approximately 0.82 mm, 1.02 mm, 1.22mm and
1.5 mm, respectively. The teeth were then mounted in 1% agar and four EALs were
used: Root ZX, Foramatron D10, Apex NRG and Apit 7. For electronic measurement,
sizes #10 and #80, #10 and #100, #10 and #120, and #10 and #140 K-files were used
for groups A, B, C and D, respectively. During electronic measurement the canals
were flushed with 6% sodium hypochlorite solution. RESULTS: Three-way ANOVA and
Bonferroni test showed that EAL, file size and foramen size all had a significant
influence on the measurement error (P<0.0001), with all the interactions between
these three factors being significant (P<0.0001). CONCLUSIONS: The four EALs were
unreliable to determine the working length of teeth with a wide apical foramen,
when using a small size file. The Root ZX and Foramatron D10 showed significantly
better scores than the other two EALs and may be more reliable to determine the
working length of teeth with a wide apical foramen, if a tight-fit file is used.
PMID- 17037895
TI - The use of a dental implant as an abutment in three unit implant-tooth supported
fixed partial denture: a case report and 32 month follow-up.
AB - The combined use of dental implants and teeth as abutments in fixed partial
dentures may offer advantages to both patients and practitioners in certain
clinical situations. An implant-tooth retained prosthesis may reduce surgical
intervention and cost to the patient. It may also mean that anatomical
restrictions to the provision of an implant-retained fixed prosthesis may be
overcome. In this case report, the steps in provision of a three unit implant-to
tooth fixed partial denture are described and the treatment planning and
prognosis of a restoration of this type are discussed.
PMID- 17037897
TI - Prevention and management of dental decay in the preschool child.
PMID- 17037896
TI - Intra-oral distribution of caries in South Australian children.
PMID- 17037898
TI - They call her 'Lucy's daughter'.
PMID- 17037899
TI - The benefits of busy.
PMID- 17037900
TI - Getting ready to roll.
PMID- 17037901
TI - The monster at our door.
PMID- 17037902
TI - 'I feel good, I feel alive'.
PMID- 17037903
TI - Beyond statins.
PMID- 17037904
TI - Frightening--and fantastic.
PMID- 17037905
TI - On-line drug metabolism in capillary electrophoresis. 1. Glucuronidation using
rat liver microsomes.
AB - A rat liver microsome pseudostationary phase has been used for the on-line
capillary electrophoresis monitoring of glucuronidation. Uridine diphosphate
glucuronosyltransferase (EC 2.4.1.17) containing microsomes was isolated from rat
liver and directly injected onto neutrally coated capillary containing polymeric
replaceable gels followed by injection of the substrate mixture. On-line
glucuronidation was observed within 15 min without any sample preparation. The
factors affecting the separation of glucuronides and parent compounds were
investigated by varying the applied electric fields and the size (length and
internal diameter) of capillary. The Michaelis-Menten parameters (Km and Vmax)
for the glucuronidation of 4-methyl-7-hydroxy coumarin and 4-nitrophenol were
determined using the CE method and by off-line microsomal incubation. No
significant differences were observed for Km and Vmax values for 4-methyl-7
hydroxycoumarin and 4-nitrophenol between on-line and off-line glucuronidation of
these two compounds. This method was also used to determine the inhibition
constant (IC50 value) for the competitive inhibition of morphine glucuronidation
by codeine, IC50 (on-line) = 170 vs 580 microM (off-line). The results
demonstrate that this method can be used to screen for the glucuronidation of
test compounds and should reduce the time required for this screening process.
PMID- 17037906
TI - Visualizing ion electromigration during isotachophoretic separations with
capillary isotachophoresis-NMR.
AB - Sample stacking techniques in electrophoresis are gaining popularity due to their
ability to provide improved sensitivity and separation efficiency. The principles
behind sample stacking and electrophoretic migration have been studied
extensively. Nevertheless, there are still a number of observations and
descriptions of ionic boundaries and migration modes for which the underlying
principles are not yet fully understood. For example, the behavior of capillary
isotachophoresis (cITP) systems that exhibit self-sharpening effects can be
complex, especially when the buffer systems contain many ionic components. In
this work, cITP coupled with 1H NMR detection is used to study electrophoretic
migration of ions in both anionic and cationic cITP. A significant advantage of
1H NMR over other detection methods is the high specificity of this method,
allowing detection of individual buffer and analyte constituents within the
migration zones.
PMID- 17037907
TI - A gas-phase chemiluminescence-based analyzer for waterborne arsenic.
AB - We show a practical sequential injection/zone fluidics-based analyzer that
measures waterborne arsenic. The approach is capable of differentiating between
inorganic As(III) and As(V). The principle is based on generating AsH3 from the
sample in a confined chamber by borohydride reduction at controlled pH, sparging
the chamber to drive the AsH3 to a small reflective cell located atop a
photomultiplier tube, allowing it to react with ozone generated from ambient air,
and measuring the intense chemiluminescence that results. Arsine generation and
removal from solution results in isolation from the sample matrix, avoiding the
pitfalls encountered in some solution-based analysis techniques. The differential
determination of As(III) and As(V) is based on the different pH dependence of the
reducibility of these species to AsH3. At pH < or =1, both As(III) and As(V) are
quantitatively converted to arsine in the presence of NaBH4. At a pH of 4-5, only
As(III) is converted to arsine. In the present form, the limit of detection (S/N
= 3) is 0.05 microg/L As at pH < or =1 and 0.09 microg/L As(III) at pH
approximately 4-5 for a 3-mL sample. The analyzer is intrinsically automated and
requires 4 min per determination. It is also possible to determine As(III) first
at pH 4.5 and then determine the remaining As in a sequential manner; this
requires 6 min. There are no significant practical interferences. A new
borohydride solution formulation permits month-long reagent stability.
PMID- 17037908
TI - Atom-transfer radical graft polymerization initiated directly from silica applied
to functionalization of stationary phases for high-performance liquid
chromatography in the hydrophilic interaction chromatography mode.
AB - Initiation of atom-transfer radical polymerization of a number of monomers
(styrene, methyl acrylate, 3-[N,N-dimethyl-N-(methacryloyloxyethyl)ammonium]
propanesulfonate, butyl methacrylate, 2,3-epoxypropyl methacrylate) directly from
chlorinated porous silica particles has been performed. The grafting has been
confirmed and evaluated by Fourier transform infrared spectroscopy and X-ray
photoelectron spectroscopy. This initiation technique results in a hydrolytically
stable initial Si-C bond, tethering the polymer to the silica substrate. The
resulting grafted particles have been used as separation materials for both
reversed-phase and hydrophilic interaction chromatography.
PMID- 17037909
TI - Nanomechanical detection of DNA melting on microcantilever surfaces.
AB - We observe surface stress changes in response to thermal dehybridization, or
melting, of double-stranded DNA (dsDNA) oligonucleotides that are grafted on one
side of a microcantilever beam. Changes in surface stress occur when one
complementary DNA strand melts and diffuses away from the other, resulting in
alterations of the electrostatic, counterionic, and hydration interaction forces
between the remaining neighboring surface-grafted DNA molecules. We have been
able to distinguish changes in the melting temperature of dsDNA as a function of
salt concentration and oligomer length. This technique also highlights
differences between surface immobilized and solution DNA melting dynamics, which
allows us to better understand the stability of DNA on surfaces. The transduction
of phase transitions into a mechanical signal is ubiquitous for DNA, making
cantilever-based detection a widely useful and complementary alternative to
calorimetric and fluorescence measurements.
PMID- 17037910
TI - Robust estimation of peptide abundance ratios and rigorous scoring of their
variability and bias in quantitative shotgun proteomics.
AB - The abundance ratio between the light and heavy isotopologues of an isotopically
labeled peptide can be estimated from their selected ion chromatograms. However,
quantitative shotgun proteomics measurements yield selected ion chromatograms at
highly variable signal-to-noise ratios for tens of thousands of peptides. This
challenge calls for algorithms that not only robustly estimate the abundance
ratios of different peptides but also rigorously score each abundance ratio for
the expected estimation bias and variability. Scoring of the abundance ratios,
much like scoring of sequence assignment for tandem mass spectra by peptide
identification algorithms, enables filtering of unreliable peptide quantification
and use of formal statistical inference in the subsequent protein abundance ratio
estimation. In this study, a parallel paired covariance algorithm is used for
robust peak detection in selected ion chromatograms. A peak profile is generated
for each peptide, which is a scatterplot of ion intensities measured for the two
isotopologues within their chromatographic peaks. Principal component analysis of
the peak profile is proposed to estimate the peptide abundance ratio and to score
the estimation with the signal-to-noise ratio of the peak profile (profile signal
to-noise ratio). We demonstrate that the profile signal-to-noise ratio is
inversely correlated with the variability and bias of peptide abundance ratio
estimation.
PMID- 17037911
TI - ProRata: A quantitative proteomics program for accurate protein abundance ratio
estimation with confidence interval evaluation.
AB - A profile likelihood algorithm is proposed for quantitative shotgun proteomics to
infer the abundance ratios of proteins from the abundance ratios of isotopically
labeled peptides derived from proteolysis. Previously, we have shown that the
estimation variability and bias of peptide abundance ratios can be predicted from
their profile signal-to-noise ratios. Given multiple quantified peptides for a
protein, the profile likelihood algorithm probabilistically weighs the peptide
abundance ratios by their inferred estimation variability, accounts for their
expected estimation bias, and suppresses contribution from outliers. This
algorithm yields maximum likelihood point estimation and profile likelihood
confidence interval estimation of protein abundance ratios. This point estimator
is more accurate than an estimator based on the average of peptide abundance
ratios. The confidence interval estimation provides an "error bar" for each
protein abundance ratio that reflects its estimation precision and statistical
uncertainty. The accuracy of the point estimation and the precision and
confidence level of the interval estimation were benchmarked with standard
mixtures of isotopically labeled proteomes. The profile likelihood algorithm was
integrated into a quantitative proteomics program, called ProRata, freely
available at www.MSProRata.org.
PMID- 17037912
TI - Surface-based lithium ion sensor: An electrode derivatized with a self-assembled
monolayer.
AB - Self-assembled monolayers (SAMs) of 21-(16-mercaptohexadecan-1-oyl)-4,7,13,16
tetraoxa-1,10,21-triazabicyclo[8.8.5]tricosane-19,23-dione were prepared on gold.
Characterization of the SAMs was carried out by sessile drop contact angle,
ellipsometry, grazing angle FT-IR spectroscopy, and electrochemical techniques.
The cation recognition properties of the SAM were studied by cyclic voltammetry
and impedance spectroscopy. The films show moderate selectivity for detection of
Li+ ions in solution over K+ and Na+, with selectivity values calculated to be
log K(Li+,Na+) approximately -1.30 and log K(Li+,K+) approximately -0.92. To the
best of our knowledge, this is the first demonstration of a lithium sensor
fabricated using self-assembled monolayer technology.
PMID- 17037913
TI - Cell-free bioassay for measurement of dioxins based on fluorescence enhancement
of fluorescein isothiocyanate-labeled DNA probe.
AB - This study aims to develop a rapid and sensitive cell-free bioassay of dioxins.
It is known that dioxin ligand can bind heterodimeric aryl hydrocarbon receptor
(AhR) and triggers the formation of the complex of dioxin-AhR, AhR nuclear
translocator (ARNT), and dioxin-responsive element (DRE) region of the DNA. The
hypothesis of the proposed method is that if FITC were labeled at the DRE
sequence, its fluorescence intensity would be enhanced when the complex forms
because the interaction interface of the binding components (AhR, ARNT, and DRE)
creates a rather hydrophobic condition that is in favor of FITC emission. Effects
of modification site of FITC on the DNA probes on binding efficiency between the
complex components and fluorescence emission enhancement were evaluated by
surface plasmon resonance and fluorescence analysis, respectively. Results showed
that the labeling site at the second base at the 5' end apart from the core
region (5'-TNGCGTG-3') of DRE did not obviously interfere with the binding
between the DNA probe and dioxin-AhR/ARNT hybrid but presented significant
fluorescence emission enhancement. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was
used as the typical toxin in this study. The method had a linear range of 1-100
pM, with detection limit of 0.1 pM (0.64 fg/assay) and coefficient of variation
of 5.6% (n = 10, 50 pM TCDD in transformed cytosol). The whole detection cycle
was approximately 4 h. The method was also used to estimate the toxic equivalents
(TEQ) of 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD) and 1,2,3,4,7,8
hexachlorodibenzo-p-dioxin (HxCDD). Measurement of TEQs of the mixture of TCDD,
PeCDD, and HxCDD were highly consistent with the predicted data. The average
recovery using fly ash extract was approximately 93%.
PMID- 17037914
TI - MALDI-MS direct tissue analysis of proteins: Improving signal sensitivity using
organic treatments.
AB - Direct tissue analysis using MALDI-MS allows the generation of profiles while
maintaining the integrity of the tissue, displaying cellular localizations and
avoiding tedious extraction and purification steps. However, lower spectral
quality can result from direct tissue analysis due to variations in section
thickness, the nature of the tissue, and the limited access to peptides/proteins
due to high lipid content. To improve signal sensitivity, we have developed a
tissue-washing procedure using organic solvents traditionally used for lipid
extraction, i.e., CHCl3, hexane, toluene, acetone, and xylene. The increased
detection for peptides/proteins (m/z 5000-30,000) is close to 40% with chloroform
or xylene, and 25% with hexane, while also improving sample reproducibility for
each solvent used in the present study. This strategy improved matrix
cocrystallization with tissue peptides/proteins and more importantly with
cytoplasmic proteins without delocalization. The extracted lipids were
characterized by nanoESI-QqTOF/MS/MS using the precursor ion mode, lithium
adducts, or both and were identified as phospholipids including
phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and
lysophosphatidylinositol, confirming membrane lipid extraction from the tissues.
PMID- 17037915
TI - Signal enhancement in HPLC/microcoil NMR using automated column trapping.
AB - A new HPLC NMR system is described that performs analytical separation,
preconcentration, and NMR spectroscopy in rapid succession. The central component
of our method is the online preconcentration sequence that improves the match
between postcolumn analyte peak volume and microcoil NMR detection volume.
Separated samples are collected on to a C18 guard column with a mobile phase
composed of 90% D2O/10% acetonitrile-D3 and back-flushed to the NMR microcoil
probe with 90% acetonitrile-D3/10% D2O. To assess the performance of our unit, we
separated a standard mixture of 1 mM ibuprofen, naproxen, and phenylbutazone
using a commercially available C18 analytical column. The S/N measurements from
the NMR acquisitions indicated that we achieved signal enhancement factors up to
10.4 (+/-1.2)-fold. Furthermore, we observed that preconcentration factors
increased as the injected amount of analyte decreased. The highest concentration
enrichment of 14.7 (+/-2.2)-fold was attained injecting 100 microL of solution of
0.2 mM (approximately 4 microg) ibuprofen.
PMID- 17037916
TI - In situ surface sampling of biological objects and preconcentration of their
volatiles for chromatographic analysis.
AB - This report describes a rolling stir bar sampling procedure for volatile organic
compounds (VOCs) present on various biological surfaces. In combination with
thermal desorption/gas chromatography/mass spectrometry, this analytical
technique was initially tested for quantitative profiling of human skin VOCs. It
is also applicable to additional hydrophobic surfaces such as agricultural
products, plant materials, and bird feathers. Use of embedded internal standards
provides highly reproducible and quantitative results for a wide variety of
sampled trace components. The samples of collected human skin VOCs and standards
were found stable under cool storage conditions for at least 14 days, making this
approach suitable for field biological and agricultural studies. Additionally,
this methodology appears to have potential for forensic and toxicological
investigations, as suggested through the analyses of VOC profiles of the human
thumb prints recovered from a nonbiological smooth surface.
PMID- 17037917
TI - Formation of silver nanoparticles in poly(perfluorosulfonic) acid membrane.
AB - The formation of silver nanoparticles by chemical reduction of Ag+-loaded Nafion
117 membrane with NaBH4 was studied using radioactivity tagged ions. The
counterion-exchange method (Ag(m)+ <--> Na(s)+) was used to obtain a membrane
sample with a varying proportion of Ag+ ions. The X-ray elemental mapping across
the thickness of the membrane by energy-dispersive X-ray spectrometer attached to
the environmental scanning electron microscope (ESEM/EDAX) indicated that Na+ and
Ag+ were uniformly distributed in the membrane samples before reduction. The
average size of nanoparticles formed after reduction was found to be 15 +/- 3 nm,
irrespective of the concentration of silver ions present in the membrane before
reduction. Energy-dispersive X-ray fluorescence (EDXRF) analyses of the membrane
samples, carried out before and after reduction, indicated that the Ag
concentration on the membrane surface was considerably increased after reduction.
EDXRF measurements of the membrane samples, obtained from reduction carried out
in a dead end cell, indicated that Ag nanoparticles were formed only on the
membrane surface exposed to NaBH4 solution. Reduction carried out with NaBH4
tagged with 22Na showed that the formation of Ag nanoparticles involved exchange
of Ag+ ions from ion-exchange sites in the interior of the membrane with Na+
ions, followed by reduction of Ag+ ions with BH4- ions at the surface of
membrane. The study of self-diffusion of water, Na+, and Cs+ ions in the membrane
loaded with Ag nanoparticles indicated that formation of Ag nanoparticles did not
affect the diffusional transport properties of the membrane. The ion-exchange
capacity and water uptake capacity were also not affected by the formation of Ag
nanoparticles in the membrane. The spatial distribution of Ag nanoparticles
across the thickness of the membrane obtained by ESEM/EDAX showed that Ag
nanoparticles were confined to a few-micrometer surface layer of the membrane.
Based on these observations, an attempt has been made to explain the mechanism of
the formation of Ag nanoparticles in the membrane.
PMID- 17037918
TI - Quantification and identification of components in solution mixtures from 1D
proton NMR spectra using singular value decomposition.
AB - One-dimensional proton NMR spectra of complex solutions provide rich molecular
information, but limited chemical shift dispersion creates peak overlap that
often leads to difficulty in peak identification and analyte quantification.
Modern high-field NMR spectrometers provide high digital resolution with improved
peak dispersion. We took advantage of these spectral qualities and developed a
quantification method based on linear least-squares fitting using singular value
decomposition (SVD). The linear least-squares fitting of a mixture spectrum was
performed on the basis of reference spectra from individual small-molecule
analytes. Each spectrum contained an internal quantitative reference (e.g., DSS
d6 or other suitable small molecules) by which the intensity of the spectrum was
scaled. Normalization of the spectrum facilitated quantification based on peak
intensity using linear least-squares fitting analysis. This methodology provided
quantification of individual analytes as well as chemical identification. The
analysis of small-molecule analytes over a wide concentration range indicated the
accuracy and reproducibility of the SVD-based quantification. To account for the
contribution from residual protein, lipid or polysaccharide in solution, a
reference spectrum showing the macromolecules or aggregates was obtained using a
diffusion-edited 1D proton NMR analysis. We demonstrated this approach with a
mixture of small-molecule analytes in the presence of macromolecules (e.g.,
protein). The results suggested that this approach should be applicable to the
quantification and identification of small-molecule analytes in complex
biological samples.
PMID- 17037919
TI - Scanning temperature gradient focusing.
AB - Temperature gradient focusing (TGF) is a recently developed technique for the
simultaneous concentration and electrophoretic separation of ionic analytes in
microfluidic channels. One drawback to TGF as it has previously been described is
the limited peak capacity; only a small number of analyte peaks (approximately 2
3) can be simultaneously focused and separated. In this paper, we report on a
variation of the TGF method whereby the bulk flow rate is varied over time so
that a large number of analytes can be sequentially focused, moved past a fixed
detection point, and flushed to waste. In addition to improved peak capacity, the
detection limits of the scanning TGF method can be adjusted on-the-fly, as needed
for different samples. Finally, scanning TGF provides a technique by which high
resolution, high-peak-capacity electrophoretic separations can be performed in
simple, straight, and short microfluidic channels.
PMID- 17037920
TI - Electron capture dissociation as structural probe for noncovalent gas-phase
protein assemblies.
AB - Electron capture dissociation (ECD) of proteins in Fourier transform ion
cyclotron resonance mass spectrometry usually leads to charge reduction and
backbone-bond cleavage, thereby mostly retaining labile, intramolecular
noncovalent interactions. In this report, we evaluate ECD of the 84-kDa
noncovalent heptameric gp31 complex and compare this with sustained off-resonance
irradiation collisionally activated dissociation (SORI-CAD) of the same protein.
Unexpectedly, the 21+ charge state of the gp31 oligomer exhibits a main ECD
pathway resulting in a hexamer and monomer, disrupting labile, intermolecular
noncovalent bonds and leaving the backbone intact. Unexpectedly, the charge
separation over the two products is highly proportional to molecular weight. This
indicates that a major charge redistribution over the subunits of the complex
does not take place during ECD, in contrast to the behavior observed when using
SORI-CAD. We speculate that the ejected monomer retains more of its original
structure in ECD, when compared to SORI-CAD. ECD of lower charge states of gp31
does not lead to dissociation of noncovalent bonds. We hypothesize that the
initial gas-phase structure of the 21+ charge state is significantly different
from the lower charge states. These structural differences result in the
different reaction pathways when using ECD.
PMID- 17037921
TI - Protein nanopatterns and biosensors using gold binding polypeptide as a fusion
partner.
AB - An efficient strategy for immobilizing proteins on a gold surface was developed
by employing the gold binding polypeptide (GBP) as a fusion partner. Using the
enhanced green fluorescent protein (EGFP), severe acute respiratory syndrome
coronavirus (SARS-CoV) envelope protein (SCVme), and core streptavidin (cSA) of
Streptomyces avidinii as model proteins, specific immobilization of the GBP
fusion proteins onto the gold nanoparticles and generation of protein
nanopatterns on the bare gold surface were demonstrated. The GBP-fused SCVme
bound to gold nanoparticles successfully interacted with its antibody and showed
changes in absorbance and color, allowing efficient diagnosis of SARS-CoV. The
fusion proteins could be successfully immobilized on the gold surface by
nanopatterning and microcontact printing as examined by atomic force microscopy
and surface plasmon resonance analysis. The poly(dimethylsiloxane) microfluidic
channels were created on the gold surface and were used for antigen-antibody and
DNA-DNA interaction studies. Specific immobilization of GBP-EGFP fusion protein
and its interaction with the antibody in the microchannels could be demonstrated.
By immobilizing the DNA probe through the use of GBP-fused cSA, specific
hybridization of the target DNA prepared from Salmonella could also be achieved.
The GBP-fusion method allows immobilization of proteins onto the gold surface
without surface modification and in bioactive forms suitable for studying protein
protein, DNA-DNA, and other biomolecular interaction studies. Furthermore, these
studies can be carried out in a microfluidic system, which allows high-throughput
analysis of biomolecular interactions.
PMID- 17037922
TI - Mesoscale energy deposition footprint model for kiloelectronvolt cluster
bombardment of solids.
AB - Molecular dynamics simulations have been performed to model 5-keV C60 and Au3
projectile bombardment of an amorphous water substrate. The goal is to obtain
detailed insights into the dynamics of motion in order to develop a
straightforward and less computationally demanding model of the process of
ejection. The molecular dynamics results provide the basis for the mesoscale
energy deposition footprint model. This model provides a method for predicting
relative yields based on information from less than 1 ps of simulation time.
PMID- 17037923
TI - In vivo glucose measurement by surface-enhanced Raman spectroscopy.
AB - This paper presents the first in vivo application of surface-enhanced Raman
scattering (SERS). SERS was used to obtain quantitative in vivo glucose
measurements from an animal model. Silver film over nanosphere surfaces were
functionalized with a two-component self-assembled monolayer, and subcutaneously
implanted in a Sprague-Dawley rat such that the glucose concentration of the
interstitial fluid could be measured by spectroscopically addressing the sensor
through an optical window. The sensor had relatively low error (RMSEC = 7.46
mg/dL (0.41 mM) and RMSEP = 53.42 mg/dL (2.97 mM).
PMID- 17037924
TI - Antigen-epitope retrieval to facilitate proteomic analysis of formalin-fixed
archival brain tissue.
AB - Formalin is a routine fixative facilitating tissue preservation and
histopathology. Proteomic techniques require freshly frozen specimens, which are
often difficult to procure, and methods facilitating proteomic analysis of
archival formalin-fixed brain tissue are lacking. We employed antigen-epitope
retrieval principles to facilitate proteomic analysis of brain tissue that had
been fixed and stored in formalin for 3-7 years. Twenty-micrometer-thick
cryopreserved OCT-embedded sections from inferior temporal cortex of human (7
years in formalin) or mouse brain specimens (3 years in formalin) were
hematoxylin-/eosin-stained. Approximately 16-64-mm2 areas of the tissue sections
were manually scraped off slides, or approximately 2 mm2 of human brain cortex
was captured off membrane-coated slides using laser microdissection. Tissue was
treated using various pH and temperature conditions prior to trypsin digestion
and nano-LC-MS/MS. The largest number of proteins were retrieved by
solubilization at pH 9 at 95 degrees C for 1 h; treatments at pH 4 or 6 at 25 or
65 degrees C were generally ineffective. Three-year formalin-fixed murine tissue
did not yield more proteins compared to human tissue. Use of formalin-fixed
tissue for proteomics is an invaluable tool for medical research. The combination
of proteomics and microdissection enables selective enrichment and identification
of novel, unique, or abundant proteins that may be important in pathogenesis.
PMID- 17037925
TI - Chitosan as a polymer for pH-induced DNA capture in a totally aqueous system.
AB - A novel DNA solid-phase extraction protocol based on the pH-dependent charge of
chitosan was developed specifically for low-volume DNA extraction on microchips.
The method uses chitosan-coated beads to extract DNA at pH 5 and release it from
the chitosan at pH 9. DNA extraction efficiency as high as 92% could be attained,
even from complex samples such as human blood containing significant amounts of
protein. Using this method, PCR inhibitors that are typically used in DNA
extraction procedures (e.g., chaotropic salts, 2-propanol) can be avoided, making
the method more conducive to downstream sample processing using PCR. A high
density multichannel microchip device was then fabricated and the microchannels
coated with chitosan for DNA extraction in an open channel configuration without
the need for an additional stationary phase. This design provided a relatively
high surface area-to-volume ratio for extraction, while retaining the low flow
resistance commensurate with open channels. With a flow rate of approximately 1
microL/min during the extraction, the total extraction time was less than 10 min,
with most of the DNA recovered in the first 2 microL of elution buffer. Using the
microchip device, extraction efficiencies for lambda-phage DNA and human genomic
DNA were as high as 67 and 63%, respectively. Human genomic DNA from whole blood
samples could be extracted in 10 min with an extraction efficiency of 75 +/- 4%
(n = 3), and the purified DNA was suitable for PCR amplification of a fragment of
the gelsolin gene. The combination of an entirely aqueous DNA extraction method
with a high-density, low-flow resistance microchannel pattern sets the stage for
future integration into microfluidic genomic analysis devices.
PMID- 17037926
TI - Tetrabutylammonium-induced coacervation in vesicular solutions of alkyl
carboxylic acids for the extraction of organic compounds.
AB - The potential of the tetrabutylammonium-induced liquid-liquid-phase separation in
alkyl carboxylic acid vesicular solutions for the extraction of organic compounds
prior to liquid chromatography was examined for the first time. The behavior of
the coacervates yielded from octanoic to oleic acids as a function of the pH and
salts was investigated. The time required for phase separation depended on the
length of the carboxylic acid alkyl chain and the experimental procedure (i.e.,
standing, sonication, centrifugation, stirring, etc.). Theoretical
preconcentration factors were a function of both surfactant concentration and the
length of the alkyl chain, and they greatly surpassed those obtained with other
surfactant-mediated separations (e.g., surfactant-rich phases from
dodecanesulfonic acid or Triton X-114). Parameters affecting the extraction
efficiency were assessed. Analytes in a wide polarity/charge range, (e.g., PAHs,
surfactants, chlorophenols, bisphenols, phthalates, herbicides, amines, dyes, and
photographic developers) were extracted with high efficiencies on the basis of
the different types of interactions that the vesicular coacervates can establish
(i.e., hydrophobic and ionic interactions, hydrogen bonds, and formation of mixed
aggregates). The coacervates were compatible with the chromatographic
determination of analytes following UV or MS detection. Their suitability for
working under real conditions was checked by applying them to the extraction of
nonionic surfactants [alkylphenol ethoxylates (octyl and nonyl) and alcohol
ethoxylates (C12-C16)] from raw and treated sewage and to river water samples.
Analytes in the coacervate were separated and quantified by liquid chromatography
ion trap mass spectrometry. No cleanup steps were necessary. Recoveries of the
target compounds in the environmental water samples ranged from 89 to 103%.
PMID- 17037927
TI - Improving an immunoassay response to related polychlorinated biphenyl analytes by
mixing antibodies.
AB - Immunoassays for detection of a class of closely related antigens, e.g., PCBs,
have often been too specific (responding strongly to some members of the class
and missing others) and no general method for adjusting the response has been
described. In this paper, the difference in the response of a model immunoassay
to different Kanechlors (Japanese commercial mixtures of PCBs, analogous to
Aroclors in the United States) is reduced from 20- or 50-fold (depending on which
antibody is used) to 3-fold when the antibodies are mixed at the proper ratio. A
mathematical model based on competitive binding of two antibodies for up to four
antigens has been developed and used to describe the assay performance and to
predict optimum mix ratios for the antibodies used. The model (based on separate
measurement of each antibody's effective Kd for each Kanechlor) provides an
excellent fit to the measured mixed antibody assay response. The model is also
successful in identifying cases where mixing monoclonal antibodies will not
improve the response. It is thought the method described will have applicability
in a variety of cases where the analytical goal is semiquantitative screening
based on the total quantity of an unknown mixture of related compounds.
PMID- 17037928
TI - Microwave-supported preparation of alpha-cellulose for analysis of delta13C in
tree rings.
AB - The microwave technique is found to be very applicable for the preparation of
alpha-cellulose from wood samples and can be recommended for analyzing the stable
carbon isotopes in tree rings. At a reaction temperature of 80 degrees C, the
extraction time can be decreased from 36 h to 15 min. Microwave-supported
prepared cellulose contains more amorphous constituents, resulting in a
relatively higher reactivity and amenability for a following nitration with
regard to determination of nonexchangeable hydrogen. The delta18O values of
microwave-enhanced extracted cellulose remain significantly lighter than
reference values, possibly as a result of an increased oxygen isotope exchange
between bleaching solution and cellulose under conditions of high energy input.
Therefore, this technique cannot be recommended for oxygen isotope analyses in
wood cellulose.
PMID- 17037929
TI - L-histidine imprinted synthetic receptor for biochromatography applications.
AB - We have proposed novel surface-imprinted beads for selective separation of
cytochrome c (cyt c) by N-methacryloyl-(L)-histidine-copper(II) [MAH-Cu(II)] as a
new metal-chelating monomer via metal coordination interactions and histidine
template. We have combined molecular imprinting with the ability of histidine to
chelate metal ions to create ligand exchange beads suitable for the binding of
cyt c (surface histidine exposed protein). The histidine imprinted beads were
produced by suspension polymerization of MAH-Cu(II)-L-histidine and ethylene
glycol dimethacrylate. After polymerization, the template (L-histidine) was
removed from the beads using methanolic KOH, thus getting histidine imprinted
metal-chelate beads. L-Histidine imprinted metal-chelate beads can be used
several times without considerable loss of cyt c adsorption capacity. The
association constant (Ka) for the specific interaction between the template
imprinted polymer and the template (L-histidine) itself were determined by
Scatchard plots using L-histidine imprinted beads and found as 58,300 M(-1).
Finally, we have used these histidine imprinted beads for cyt c and ribonuclease
A (surface histidine exposed proteins) and enantiometric separation of D- and L
histidine by FPLC.
PMID- 17037930
TI - Structural features of the L-argininamide-binding DNA aptamer studied with ESI
FTMS.
AB - The 24-mer DNA aptamer of Harada and Frankel (Harada, K.; Frankel, A. D. EMBO J.
1995, 14, 5798-5811) that binds L-argininamide (L-Arm) was studied by
electrospray ionization Fourier transform mass spectrometry (ESI-FTMS). This DNA
folds into a stem and loop such that the loop is able to engulf L-Arm. As
controls, two derivatives of the same base composition, one with the same stem
but a scrambled loop and the other with no ability to form a secondary structure,
were studied. The two DNAs that could fold into stem-loop structures showed a
more negatively charged distribution of ions than the linear control. This
tendency was preserved in the presence of ligand; complexes expected to have more
secondary structure had ions with more negative charges. Distinct species
corresponding to no, one, and two bound L-Arm molecules were observed for each
DNA. The fractional peak intensities were fit to a straightforward binding model
and binding constants were obtained. Thus, ESI-FTMS can provide both qualitative
and quantitative data regarding the structure of DNA and its interactions with
noncovalent ligands.
PMID- 17037932
TI - Determination of the bulk cobalt valence state of co-perovskites containing
surface-adsorbed impurities.
AB - We used thermogravimetric hydrogen reduction and iodometric titration to
determine the bulk valence state of cobalt in Co-perovskites containing surface
carbonate hydroxide or hydroxyl groups. It could be shown that thermogravimetric
hydrogen reduction experiments are very sensitive to volatile surface groups, but
due to their volatility, they can be specified and the bulk valence state of
cobalt can still be deduced from these experiments. The iodometric titration is
less sensitive to small volatile surface impurities, but precaution has to be
taken that oxygen or iodine does not escape from the solution during dissolution
of the sample. Best results were obtained if the sample was titrated during
dissolution in a closed argon floated titration apparatus. We tested the two
methods using LaCoO3 perovskite as a sample with a known valence state. Both
methods delivered satisfactory results, and the valence state could be determined
with an accuracy of better than 1%.
PMID- 17037931
TI - Profiling signaling peptides in single mammalian cells using mass spectrometry.
AB - The peptide content of individual mammalian cells is profiled using matrix
assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry.
Both enzymatic and nonenzymatic procedures, including a glycerol cell
stabilization method, are reported for the isolation of individual mammalian
cells in a manner compatible with MALDI MS measurements. Guided microdeposition
of MALDI matrix allows samples to be created with suitable analyte-to-matrix
ratios. More than 15 peptides are observed in individual rat intermediate
pituitary cells. The combination of accurate mass data, expected cleavages by
proteolytic enzymes, and postsource decay sequencing allows identification of 14
of these peptides as pro-opiomelanocortin prohormone-derived molecules. These
protocols permit the classification of individual mammalian cells by peptide
profile, the elucidation of cell-specific prohormone processing, and the
discovery of new signaling peptides on a cell-to-cell basis in a wide variety of
mammalian cell types.
PMID- 17037933
TI - Generation of ultrahigh peak capacity LC separations via elevated temperatures
and high linear mobile-phase velocities.
AB - The use of a combination of ultraperformance liquid chromatography at
approximately 11,000 psi on sub 2-microm particles combined with reversed-phase
gradient chromatography at a temperature of 90 degrees C is described as applied
to the analysis of endogenous and drug metabolites in human and animal urine. By
using elevated temperatures, back pressures can be reduced while maintaining high
flow rates and chromatographic efficiency, with peaks 1-3 s wide at the base.
Application to urine samples provided a peak capacity of approximately 700 for a
10-min analysis and greater than approximately 1000 in 1 h. Despite the narrow
nature of the peaks, good quality mass spectra were also obtained, allowing the
identification of typical drug and endogenous metabolites. These ultra-high
resolution chromatograms should be ideal for the analysis of complex samples in,
for example, metabolite identification, impurity identification, and
metabonomic/metabolomic studies. Applications in natural product analysis and
proteomics can also be envisaged.
PMID- 17037934
TI - Measurement of ammonia in human breath with a liquid-film conductivity sensor.
AB - Measurement of breath NH3 is of interest in clinical applications as it can be
used as a measure of kidney/liver functions as well as halitosis. We have
developed a liquid-film conductivity sensor to measure NH3 in human breath. A
film of dilute H2SO4 is formed on the top of two metal capillary tubes placed in
a concentric annular arrangement. The tube exterior has been specially treated to
render it hydrophilic. As breath passes over the sensor tip, the film collects
NH3 and the solution conductivity (measured by the concentric capillaries
functioning as electrodes) decreases accordingly. This initial rate of
conductivity decrease was determined to be the best metric (most rapid and least
dependent on breath pCO2) for ammonia, relative to time to attain complete
neutralization (conductivity minimum) or the final rate of conductivity increase
as more ammonia dissolves after neutralization. The absorbing solution
composition was optimized so that CO2 does not interfere. Both dynamic
measurement using mask sampling and offline balloon sampling were performed.
Ammonia readily absorbs on surfaces when significant concentrations of water
vapor are present. As such, memory effects are common when analyzing human breath
for ammonia. This problem was successfully eliminated. The results from this
sensor agreed well with data obtained by a solution-phase fluorometric technique
using a porous membrane diffusion scrubber and o-phthalaldehyde derivatization
chemistry. For breath CO2 measurement, the applicability of a similar sensor that
relies on a NaOH film was also demonstrated.
PMID- 17037935
TI - Injection port derivatization following ion-pair hollow fiber-protected liquid
phase microextraction for determining acidic herbicides by gas
chromatography/mass spectrometry.
AB - Injection port derivatization following ion-pair hollow fiber-protected liquid
phase microextraction (LPME) for the trace determination of acidic herbicides
(2,4-dichlorobenzoic acid, 2,4-dichlorophenoxyacetic acid, 2-(2,4
dichlorophenoxy)propionic acid, 3,5-dichlorobenzoic acid, 2-(2,4,5
trichlorophenoxy)propionic acid) in aqueous samples by gas chromatography/mass
spectrometry (GC/MS) was developed. Prior to GC injection port derivatization,
acidic herbicides were converted into their ion-pair complexes with
tetrabutylammonium chloride in aqueous samples and then extracted by 1-octanol
impregnated in the hollow fiber. Upon injection, ion pairs of acidic herbicides
were quantitatively derivatized to their butyl esters in the GC injection port.
Thus, several parameters related to the derivatization process (i.e., injection
temperature, purge-off time) were evaluated, and main parameters affecting the
hollow fiber-protected LPME procedure such as extraction organic solvent, ion
pair reagent type, pH of aqueous medium, concentration of ion-pair reagent,
sodium chloride concentration added to the aqueous medium, stirring speed, and
extraction time profile, optimized. At the selected extraction and derivatization
conditions, no matrix effects were observed. This method proved good
repeatability (RSDs <12.3%, n = 6) and good linearity (r2 > or = 0.9939) for
spiked deionized water samples for five analytes. The limits of detection were in
the range of 0.51-13.7 ng x L(-1) (S/N =3) under GC/MS selected ion monitoring
mode. The results demonstrated that injection port derivatization following ion
pair hollow fiber-protected LPME was a simple, rapid, and accurate method for the
determination of trace acidic herbicides from aqueous samples. In addition, this
method proved to be environmentally friendly since it completely avoided open
derivatization with potentially hazardous reagents.
PMID- 17037936
TI - Low-cost spectroscopy with a variable multivariate optical element.
AB - Here, successful realization of a variable multivariate optical element (VMOE)
based on a transmissive liquid crystal (LC) panel is reported. In contrast to
conventional multivariate optical elements (MOEs), a single VMOE is a dynamic
system, allowing measurement of numerous analytes in different mixtures.
Furthermore, VMOE has superior spectral resolution in comparison to a
conventional MOE. It is demonstrated here that the system implemented in a Raman
spectrometer predicts the concentration of each individual component in toluene
acetonitrile-cyclohexane mixtures with a prediction error of <6% (mass
percentage). With a dedicated optical design of the setup, a prediction error
smaller than 2% is expected to be feasible for the current chemical system.
PMID- 17037937
TI - Analysis of complex protein mixtures with improved sequence coverage using (CE
MS/MS)n.
AB - Identification of proteins, in a complex protein mixture, using one-dimensional
high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS)
analysis of its digest, usually suffers from low sequence coverage. There are
several reasons for the low coverage including undersampling, wide concentration
dynamic range of the proteins in a complex protein mixture, and wide range of
electrospray ionization efficiency of peptides under each mobile-phase
composition. To address this low sequence coverage, we introduce a novel
technique, (CE-MS/MS)n, which utilizes the most significant advantages of CE
MS/MS, including economy of sample size, fast analysis time, and high separation
efficiency, to increase the sequence coverage of a complex protein mixture. Based
on these characteristics, (CE-MS/MS)n can be performed in which multiple CE-MS/MS
subanalyses (injections followed by analyses) are analyzed and experimental
variables are manipulated during each CE-MS/MS subanalysis in order to maximize
sequence coverage. (CE-MS/MS)n is a practical technique since each CE-MS/MS
subanalysis consumes <10 nL, and each CE-MS/MS subanalysis takes approximately 10
min; therefore, several subanalyses can be performed in approximately 1 h
consuming only nanoliters of the sample. Two techniques have been introduced to
address the undersampling: (1) (CE-MS/MS)n using dynamic exclusion. In this
technique, several CE-MS/MS analyses (injection followed by separation) were
performed in one run using the dynamic exclusion capability of the mass
spectrometer until all peptide peaks were analyzed by MS/MS. (2) Gas-phase
fractionation. In this technique, (CE-MS/MS)n is performed by scanning a narrow
mass range (every approximately 100 m/z) during each CE-MS/MS subanalysis without
using dynamic exclusion. Under this condition, in each subanalysis, the number of
peptides available for MS/MS analysis is significantly reduced, and peptides with
the same nominal masses are analyzed, thereby increasing sequence coverage.
Additionally, to address the lack of detection of low-level peptides in a mixture
containing a wide concentration dynamic range, the concentration of the sample
was systematically increased in each subanalysis (while utilizing dynamic
exclusion) so that low-intensity peptides would rise above the mass spectrometer
threshold and, consequently, undergo MS/MS analysis. Moreover, to alter the
ionization efficiency of peptides with low electrospray ionization efficiency,
and to change the migration behavior of comigrating peptides under a specific
liquid composition, the CE background electrolyte was modified in several
subanalyses to further improve sequence coverage. The combination of the above
mentioned techniques was applied to the analysis of the tryptic digests of three
well-characterized protein mixtures: a six-protein mixture with average MW of
approximately 26,000 (standard I), a six-protein mixture with an average MW
approximately 49,000 (standard II), and a more complex protein mixture containing
55 proteins (E. coli ribosomal proteins). In approximately 1 h, when the MS/MS of
the peptides were manually checked, all peptides that produced peaks under
electrospray ionization in the scanned range of the analysis (500-2000 m/z) and
within the practical fragmentation capability of the MS (peptides with MW <3500)
were identified for standard I by consuming only 200 fmol of each protein. When
searched against a Swissprot database, the average sequence coverage for the
standard I, II, and E. coli's ribosomal proteins were 57, 34, and 15%,
respectively.
PMID- 17037938
TI - Feedback-independent Pt nanoelectrodes for shear force-based constant-distance
mode scanning electrochemical microscopy.
AB - A new generation of platinum nanoelectrodes for constant-distance mode scanning
electrochemical microscopy (CD-SECM) has been prepared, characterized, and used
for high spatial resolution electrochemical measurements and visualization of
electrochemically induced concentration gradients in microcavities. The probes
have long (1-2 cm), narrow quartz tips that were conically polished and have a Pt
nanoelectrode that is slightly offset from center. Because of the size and
location of the electrode on the probe, it does not exhibit SECM feedback while
approaching the analyzed sample surfaces even to distances within a few hundred
nanometers. The probe was positioned near the surface while scanning and
performing electrochemical measurements through use of nonoptical shear force
control of the tip-to-sample distance. Test structures consisted of cylindrically
shaped microcavities that are 50 microm in diameter with three individually
addressable electrodes: a gold disk at 8-microm depth, a crescent-shaped gold
ring at 4-microm depth along the wall, and a top gold electrode at the rim.
Different electrodes within the microcavity were used to reduce and oxidize redox
species in 250 microL of a solution of 5 mM hexaamineruthenium(III) chloride and
0.1 M potassium chloride, protected from evaporation by mineral oil, while the
SECM tip followed the topography of the structures and monitored the current from
the oxidation of [Ru(NH3)6]2+. Electrochemically generated concentration profiles
were obtained from these complex test structures that are not possible with any
other SECM technology at this time.
PMID- 17037939
TI - Conductance maps by electrochemical tunneling spectroscopy to fingerprint the
electrode electronic structure.
AB - We describe a methodology to perform reliable tunneling spectroscopy in
electrochemical media. Sequential in situ tunneling spectra are recorded while
the electrochemical potential of the electrode is scanned. Spectroscopic data are
presented as conductance maps or conductograms that show the in situ electronic
structure of an electrode surface while it undergoes an electrochemical reaction.
The conductance map or conductogram represents the redox fingerprint of an
electrode/liquid interface in a specific medium and can serve to predict its
electrochemical behavior in a quantitative energy scale. The methodology is
validated studying the reversible oxidation and passivity of an iron electrode in
borate buffer, and we describe the main quantitative information that can be
extracted concerning the semiconducting properties of the Fe passive film. This
methodology is useful to study heterogeneous catalysis, electrochemical sensing
and bioelectronic systems.
PMID- 17037940
TI - Electrochemiluminescent detection based on solid-phase extraction at tris(2,2'
bipyridyl)ruthenium(II)-modified ceramic carbon electrode.
AB - A sensitive electrochemiluminescent detection scheme by solid-phase extraction at
Ru(bpy)3(2+)-modified ceramic carbon electrodes (CCEs) was developed. The as
prepared Ru(bpy)3(2+)-modified CCEs show much better long-term stability than
other Nafion-based Ru(bpy)3(2+)-modified electrodes and enjoy the inherent
advantages of CCEs. The log-log calibration plot for dioxopromethazine is linear
from 1.0 x 10(-9) to 1.0 x 10(-4) mol L(-1) using the new detection scheme. The
detection limit is 6.6 x 10(-10) mol L(-1) at a signal-to-noise ratio of 3. The
new scheme improves the sensitivity by approximately 3 orders of magnitude, which
is the most sensitive Ru(bpy)3(2+) ECL method. The scheme allows the detection of
dioxopromethazine in a urine sample within 3 min. Since Ru(bpy)3(2+) ECL is a
powerful technique for determination of numerous amine-containing substances, the
new detection scheme holds great promise in measurement of free concentrations,
investigation of protein-drug interactions and DNA-drug interactions,
pharmaceutical analysis, and so on.
PMID- 17037941
TI - Grating-coupler assisted infrared reflection absorption spectroscopy for the
characterization of organic thin films.
AB - We demonstrate how grating-coupler assisted infrared reflection absorption
spectroscopy can be used to simultaneously determine the chemical identity and
relative thickness of organic thin films. With a grating substrate, a threshold
anomaly associated with passing off of the -1 diffracted order occurs at grazing
angles of incidence, resulting in a sharp absorbance in the infrared. The
position of this peak is sensitive to the grating geometry as well as the
dielectric environment near its surface. Thus, shifts in the peak position can be
used to determine the relative thickness of adsorbed films or quantify molecular
adsorption events. To illustrate the characteristics and sensitivity of this
phenomenon, several samples were prepared and tested, including self-assembled
alkanethiolate monolayers with 11-mercaptoundecanoic acid, 11-mercapto-1
undecanol, decanethiol, and a covalently linked layer of bovine serum albumin on
a commercial, gold-coated grating. For these samples, the position of the
threshold absorbance peak shifted to lower wavenumbers as film thickness
increased, which is consistent with calculated shifts based upon an increasing
refractive index at the interface. The sensitivity of this shift was measured to
be 3.7 cm(-1) nm(-1). These results illustrate how a grating substrate can be
exploited in a standard infrared reflectance measurement to provide additional
information about the relative thickness of adsorbed surface films.
PMID- 17037942
TI - Atomic force microscopy study of different effects of natural and semisynthetic
beta-lactam on the cell envelope of Escherichia coli.
AB - The effects of native and semisynthetic beta-lactam on the surface of E. coli
cells were investigated using tapping mode atomic force microscopy (AFM). These
studies were done on both single cell and cell colonies. This allowed us to
achieve a complete understanding of the effects, since previous related AFM
analysis was only performed on single cells. Our results indicated that although
amoxycillin and penicillin could both induce nanoporous damage to the envelope of
E. coli, the distribution of the pores was different: those induced by penicillin
were randomly distributed on the cell surface, while those induced by amoxycillin
were far more numerous and mainly on the two ends of the cell. These findings
could explain why the effect of amoxycillin is stronger than that of native
penicillin. Ofloxacin was used as a control due to its inactive membrane, and no
cell wall damages were observed. Our results demonstrate that AFM is a useful
tool in discerning and verifying antibiotic mechanisms and can be helpful to
explain the relationship between chemical structure and the function of
antibiotics.
PMID- 17037943
TI - Simultaneous excitation of propagating and localized surface plasmon resonance in
nanoporous gold membranes.
AB - Materials multifunctionality for optical sensing of adsorbates has obvious
advantages-in addition to the potential for greater sensitivity, the different
length scales associated with a variety of optical phenomena allow a greater
variety of adsorption characteristics to be examined. Here, we show that
ultrathin (approximately 100 nm) nanoporous gold membranes possess features of
both planar metal films that exhibit propagating SPR excitations and nanofeatured
metals that exhibit localized SPR excitations. This is the first report of such
multifunctionality in an optically active metal. We give illustrative examples of
using this material to probe biorecognition reactions and to probe the structure
evolution of a layer-by-layer deposition of charged dendrimers. Our results are
consistent with the very different lengths of the tail of the evanescent field
decays associated with each of these plasmon excitation modes.
PMID- 17037945
TI - Clinical trials research in pediatrics: strategies for effective collaboration
between investigator sites and the pharmaceutical industry.
AB - There is a paucity of clinical trials work in children, which leads to the
frequent use of off-label and unlicensed medications in this very vulnerable
group. Clinical trials work in children may be more difficult than in adults, and
there are certainly ethical constraints. However, the differences between adults
and children, and at different stages of childhood development, mandate
strategies to improve this situation rather than continually relying on
extrapolation from adult studies. Therefore, new strategies have to be
established between the pharmaceutical industry and pediatric centers to
facilitate effective trials work. These must be based on a clear and mutual
understanding of the differences between working with children and adults.
Disease phenotypes may be completely different in children; for example, wheeze
in infants is not miniature adult asthma. Clinical trial design must be
practical, and a trial is more likely to succeed if a simple design is utilized,
with minimal interference with school work and the work of carers. The new UK
initiative, 'Medicines for Children', should go a long way towards addressing the
problem, and increase the evidence base for the utilization of medications in
pediatric practice.
PMID- 17037947
TI - Juvenile myoclonic epilepsy: epidemiology, pathophysiology, and management.
AB - Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome that begins most
frequently in the early teenage years. It is officially classified as a type of
idiopathic generalized epilepsy and is often under-recognized or misdiagnosed.
This syndrome has a strong genetic component with multiple gene mutations being
associated with the clinical presentation. Based upon genetic associations, there
may be multiple pathophysiologic mechanisms for the disorder; the pathophysiology
has not been clearly defined. A diagnosis of JME is made using the clinical
history and EEG findings. Valproic acid is the primary antiepileptic drug (AED)
used for JME, but some newer AEDs may be effective alternatives. Selection of an
appropriate AED is essential to the proper management of JME, because of the
possibility of exacerbation of seizures by some AEDs and the adverse effect
profiles of effective drugs. It is important for clinicians to understand JME to
correctly diagnose and manage patients with this syndrome.
PMID- 17037948
TI - Polycystic ovary syndrome in adolescents: current and future treatment options.
AB - Polycystic ovary syndrome (PCOS) is a very common disorder affecting 5-10% of
women of reproductive age. The pivotal endocrine abnormalities of this syndrome
are insulin resistance and ovarian and, to a lesser degree, adrenal
hypersensitivity to hormonal stimulation. PCOS may manifest itself as early as
the first decade of life by premature pubarche or menarche. Oligoamenorrhea in
the first postpubarchal years, although very common, may be an early symptom of
PCOS, especially in overweight girls with hirsutism or acne. Girls with low birth
weight as well as a family history of diabetes mellitus or premature
cardiovascular disease are at high risk for developing PCOS. Circulating
bioavailable testosterone levels are usually elevated, while total testosterone
may be normal due to low levels of sex hormone-binding globulin. The typical
sonographic appearance of PCOS ovaries consists of high ovarian volume (>10 mL)
and the presence of 12 or more follicles in each ovary measuring 2-9 mm in
diameter. However, this finding is not specific, since it may occur in >20% of
healthy girls. The therapeutic goals in adolescents with PCOS is first to restore
bodyweight and menses and to reduce the signs of hyperandrogenism. The reduction
of bodyweight in this young age group may require the collaboration of the
pediatrician, dietitian, and psychotherapist. The adolescent should be urged to
adopt a healthy lifestyle with the aim to maintain a normal body mass index
throughout adolescence and adult life. The choice of medical therapy depends on
the clinical presentation. Oral contraceptives are a good option when acne and
hirsutism are the principal complaints. Adolescents with isolated cycle
irregularity may be placed on a cyclical progestin regimen to induce withdrawal
bleeding. Metformin, by decreasing insulin resistance, alleviates many of the
hormonal disturbances and restores menses in a considerable proportion of
patients. It may be used alone or in combination with oral contraceptives.
Independently of medical treatment, restoration and maintenance of bodyweight
within normal range is of paramount importance.
PMID- 17037946
TI - Current therapy of inflammatory bowel disease in children.
AB - Ulcerative colitis (UC) and Crohn disease (CD) are chronic intestinal
inflammatory diseases that can present as bloody diarrhea, abdominal pain, and
malnutrition. Collectively, these disorders are referred to as inflammatory bowel
disease (IBD). All patients with IBD share a common pathophysiology. However,
there are a number of developmental, psychosocial, and physiologic issues that
are unique to the approximate, equals 20% of patients that present during
childhood or adolescence. These include the possibility of disease-induced delays
in linear growth or physical development, differences in drug dosing, and the
changes in social and cognitive development that occur as children move from
school-age years into adolescence and early adulthood. Gastroenterologists caring
for these children must therefore develop an optimal regimen of pharmacologic
therapies, nutritional management, psychologic support, and properly timed
surgery (when necessary) that will maintain disease remission, minimize disease
and drug-induced adverse effects, and optimize growth and development. This
article reviews current approaches to the management of patients with UC and CD
and highlights issues specific to the treatment of children with IBD. The
principal medical therapies used to induce disease remission in patients with UC
are aminosalicylates (for mild disease), corticosteroids (for moderate disease),
and cyclosporine (ciclosporin) (for severe disease). If a patient responds to the
induction regimen, maintenance therapies that are used to prevent disease relapse
include aminosalicylates, mercaptopurine, and azathioprine. Colectomy with
creation of an ileal pouch anal anastomosis (J pouch) has become the standard of
care for patients with severe or refractory colitis and results in an improved
quality of life in most patients. Therefore, the risks associated with using
increasingly potent immunosuppressant agents must be balanced in each case
against a patient's desire to retain their colon and avoid a temporary or
potentially permanent ileostomy. Decisions about drug therapy in the management
of patients with CD are more complex and depend on both the location (e.g.
gastroduodenal vs small intestinal vs colonic), as well as the behavior of the
disease (inflammatory/mucosal vs stricturing vs perforating) in a given patient.
Induction therapies for CD typically include aminosalicylates and antibiotics
(for mild mucosal disease), nutritional therapy (including elemental or polymeric
formulas), corticosteroids (for moderate disease), and infliximab (for
corticosteroid-resistant or fistulizing disease). Aminosalicylates,
mercaptopurine, azathioprine, methotrexate, and infliximab can be used as
maintenance therapies. Because surgical treatment of CD is not curative, it is
typically reserved for those patients either with persistent symptoms and disease
limited to a small section of the intestine (e.g. the terminal ileum and cecum)
or for the management of complications of the disease including stricture or
abdominal abscess. When surgery is necessary, maintenance medications
administered postoperatively will postpone recurrence. Patients with UC and CD
are at risk for the development of micronutrient deficiencies (including folate,
iron, and vitamin D deficiencies) and require close nutritional monitoring. In
addition, patients with UC and CD involving the colon are at increased risk of
developing colon cancer, and should be enrolled into a colonoscopy surveillance
program after 8-10 years of disease duration.
PMID- 17037949
TI - Methylphenidate controlled-delivery capsules (EquasymXL, Metadate CD): a review
of its use in the treatment of children and adolescents with attention-deficit
hyperactivity disorder.
AB - Controlled-delivery methylphenidate (methylphenidate CD) [EquasymXL, Metadate
CD], an oral stimulant, is approved in the US and EU to treat children aged>or=6
years who have been diagnosed with attention-deficit hyperactivity disorder
(ADHD). Once-daily methylphenidate CD is generally well tolerated and effective
in the treatment of children and adolescents with ADHD. Methylphenidate CD
resulted in superior control of ADHD symptoms compared with osmotic release oral
system (OROS) methylphenidate over a time period corresponding to that of an
average school day in a laboratory classroom. In 3-week clinical trials conducted
in a community setting, methylphenidate CD was superior to placebo and
noninferior to methylphenidate immediate-release (IR) in the treatment of
children and adolescents with ADHD. Thus, methylphenidate CD should be considered
an important primary treatment on its own or in addition to behavioral and
psychosocial interventions, for when a reduction in ADHD symptoms is required
during the school day in preference to the evening.
PMID- 17037950
TI - The relations between personality characteristics, work environment, and the
professional well-being of music therapists.
AB - The purpose of this correlational study was to investigate the relations between
professional well-being (as characterized by positive attitudes toward work and
longevity as a practicing music therapist) and the following factors: age, level
of education, income, attitudes regarding the workplace (e.g., perceived control,
feeling valued, as well as the amount of perceived comfort and input into
administrative policies), attitudes toward work as measured by the Maslach
Burnout Inventory (Maslach & Jackson, 1986a), and measures of stress and stress
management as measured by the Stress Profile (Nowack, 1999a). Participants
included 49 music therapists who had between one to 36 years of work experience.
Correlations indicated that those respondents with greatest professional
longevity tended to have higher ratings on items regarding cognitive coping
strategies (e.g., positive appraisal and threat minimization) and greater
perception of personal achievement. These correlational results are related to
psychological theories regarding occupational burnout and cognitive hardiness.
PMID- 17037951
TI - Emotional communicability in improvised music: the case of music therapists.
AB - Musical improvisation is considered an efficient way to express emotions in music
therapy. We examined the ability of music therapists (MTs) to convey emotions and
their ability to accurately decode the emotional content of musical
improvisations. Twenty-one MTs improvised on emotions they found difficult or
easy to express in life, using or not using an emotional imagery technique. Fifty
five judges, some being MTs others nontherapists, evaluated the emotional content
of the improvisations. Results showed that neither experience in therapy, nor
musicianship or gender of the improviser were connected to emotional
communicability (EC). Emotions that were reported as easy to express in life were
communicated more accurately than those difficult to express in life. Emotional
imagery did not facilitate and, to some extent, hindered emotional
communicability. Some emotions were found to be difficult to express (e.g.,
anger) in comparison to others (e.g., happiness). MTs decoded the emotional
content of the improvisations more accurately than nontherapists. Implications
for the practical musical and emotional training of music therapists are
discussed.
PMID- 17037952
TI - Value of musical instruments used by the therapist to elicit responses from
individuals in various stages of Alzheimer's disease.
AB - The purpose of this study was to determine the value of designated musical
instruments used by the therapist to elicit responses from persons with
Alzheimer's disease (AD) during group sessions. In Experiment 1, 15 individuals
in the early and middle stages of AD echoed rhythm patterns played by the
therapist via the djembe, claves, paddle drum, and maraca. Results indicated
significance for the rhythm patterns used, p < .05, and the types of instruments
used, p < .05. A significant difference occurred for interaction of instruments
by rhythms, p < .001. Rhythmic accuracy was highest when the therapist presented
rhythms on the djembe, followed by the paddle drum, maraca, and claves. The most
accurate rhythm pattern was 8 eighth-notes, the second most accurate was 4
quarter-notes, and the third was 2 eighths followed by a quarter note, repeated.
Ten individuals in the middle to later stages of AD participated in Experiment 2.
The treatment conditions consisted of 6 musical instruments used by the
therapists to elicit responses during movement, singing, and rhythm activities.
Average participation at any level (singing and moving/playing, singing only, and
moving/playing only) in the 6 treatment conditions was highest during a cappella
singing (63%), followed by djembe (61%), keyboard (60%), guitar and djembe (57%),
and then guitar (54%) and autoharp (54%). Average participation at any level in
the four activities, without any consideration of instruments, was as follows:
83% for the rhythm activity, 51% for the movement activity, and 49% for the first
as well as second singing activity. Results indicated significant differences for
the treatment conditions, p < .001, and for types of activities, p < .05.
Significant difference, p < .01, occurred for interaction of treatment condition
by activity.
PMID- 17037953
TI - Use of preferred music to reduce emotional distress and symptom activity during
radiation therapy.
AB - Music therapy has decreased anxiety levels in many medical settings. This
randomized clinical trial examined the effectiveness of a music listening
intervention, delivered by a board-certified music therapist, in patients
undergoing curative radiation therapy (RT). Emotional distress (anxiety,
depression, and treatment-related distress) and symptoms (fatigue and pain) were
measured at baseline, mid-treatment, and end of treatment in 63 patients
undergoing RT. Although patients who listened to self-selected music reported
lower anxiety and treatment-related distress, there was a decline in these
outcomes for patients in both groups over the course of RT. Depression, fatigue,
and pain were not appreciably affected by music therapy. Within the music group,
there was a significant correlation between number of times music was used/week
and the change in treatment-related distress, suggesting that higher doses of
music produced greater declines in distress. While these findings provided some
support for the use of music in reducing distress during RT, further research
demonstrating clear differences between intervention and control conditions is
needed. Physical symptoms were not affected by the use of music over the course
of RT.
PMID- 17037958
TI - A polynomial-time algorithm for de novo protein backbone structure determination
from nuclear magnetic resonance data.
AB - We describe an efficient algorithm for protein backbone structure determination
from solution Nuclear Magnetic Resonance (NMR) data. A key feature of our
algorithm is that it finds the conformation and orientation of secondary
structure elements as well as the global fold in polynomial time. This is the
first polynomial-time algorithm for de novo high-resolution biomacromolecular
structure determination using experimentally recorded data from either NMR
spectroscopy or X-ray crystallography. Previous algorithmic formulations of this
problem focused on using local distance restraints from NMR (e.g., nuclear
Overhauser effect [NOE] restraints) to determine protein structure. This approach
has been shown to be NP-hard, essentially due to the local nature of the
constraints. In practice, approaches such as molecular dynamics and simulated
annealing, which lack both combinatorial precision and guarantees on running time
and solution quality, are used routinely for structure determination. We show
that residual dipolar coupling (RDC) data, which gives global restraints on the
orientation of internuclear bond vectors, can be used in conjunction with very
sparse NOE data to obtain a polynomial-time algorithm for structure
determination. Furthermore, an implementation of our algorithm has been applied
to six different real biological NMR data sets recorded for three proteins. Our
algorithm is combinatorially precise, polynomialtime, and uses much less NMR data
to produce results that are as good or better than previous approaches in terms
of accuracy of the computed structure as well as running time.
PMID- 17037959
TI - Wavelet analysis of DNA walks.
AB - A wavelet transform of the DNA "walk" constructed from a genomic sequence offers
a direct visualization of short and long-range patterns in nucleotide sequences.
We study sequences that encode diverse biological functions, taken from a variety
of genomes. Pattern irregularities in the transform are frequently associated
with sequences of biological interest. Exonic regions, for example, visualize
differently under wavelet analysis than introns, and ribosomal RNA regions
display distinct universal signatures. DNA walk wavelet analysis can provide a
sensitive and rapid assessment of the putative biological significance of genomic
DNA.
PMID- 17037960
TI - Detecting conserved interaction patterns in biological networks.
AB - Molecular interaction data plays an important role in understanding biological
processes at a modular level by providing a framework for understanding cellular
organization, functional hierarchy, and evolutionary conservation. As the quality
and quantity of network and interaction data increases rapidly, the problem of
effectively analyzing this data becomes significant. Graph theoretic formalisms,
commonly used for these analysis tasks, often lead to computationally hard
problems due to their relation to subgraph isomorphism. This paper presents an
innovative new algorithm, MULE, for detecting frequently occurring patterns and
modules in biological networks. Using an innovative graph simplification
technique based on ortholog contraction, which is ideally suited to biological
networks, our algorithm renders these problems computationally tractable and
scalable to large numbers of networks. We show, experimentally, that our
algorithm can extract frequently occurring patterns in metabolic pathways and
protein interaction networks from the KEGG, DIP, and BIND databases within
seconds. When compared to existing approaches, our graph simplification technique
can be viewed either as a pruning heuristic, or a closely related, but
computationally simpler task. When used as a pruning heuristic, we show that our
technique reduces effective graph sizes significantly, accelerating existing
techniques by several orders of magnitude! Indeed, for most of the test cases,
existing techniques could not even be applied without our pruning step. When used
as a stand-alone analysis technique, MULE is shown to convey significant
biological insights at near-interactive rates. The software, sample input graphs,
and detailed results for comprehensive analysis of nine eukaryotic PPI networks
are available at www.cs.purdue.edu/homes/koyuturk/mule.
PMID- 17037961
TI - Settling the intractability of multiple alignment.
AB - Multiple alignment is a core problem in computational biology that has received
much attention over the years, both in the line of heuristics and hardness
results. In most expositions of the problem it is referred to as NP-hard and
references are given to one of the available hardness results. However, previous
to this paper not even the most elementary variation of the problem, multiple
alignment under the unit metric, had been proved hard. The aim of this paper is
to settle the NP-hardness of the most common variations of multiple alignment.
The following variations are shown NP-hard for all metrics over binary or larger
alphabets: MULTIPLE ALIGNMENT WITH SP-SCORE, STAR ALIGNMENT, and TREE ALIGNMENT
(for a given phylogeny). In addition, NP-hardness results are provided for
CONSENSUS PATTERNS and SUBSTRING PARSIMONY.
PMID- 17037962
TI - On the similarity of sets of permutations and its applications to genome
comparison.
AB - The comparison of genomes with the same gene content relies on our ability to
compare permutations, either by measuring how much they differ, or by measuring
how much they are alike. With the notable exception of the breakpoint distance,
which is based on the concept of conserved adjacencies, measures of distance do
not generalize easily to sets of more than two permutations. In this paper, we
present a basic unifying notion, conserved intervals, as a powerful
generalization of adjacencies, and as a key feature of genome rearrangement
theories. We also show that sets of conserved intervals have elegant nesting and
chaining properties that allow the development of compact graphic
representations, and linear time algorithms to manipulate them.
PMID- 17037963
TI - Optimizing multiple spaced seeds for homology search.
AB - Optimized spaced seeds improve sensitivity and specificity in local homology
search. Several authors have shown that multiple seeds can have better
sensitivity and specificity than single seeds. We describe a linear programming
(LP)-based algorithm to optimize a set of seeds. Theoretically, our algorithm
offers a performance guarantee: the sensitivity of a chosen seed set is at least
70% of what can be achieved, in most reasonable models of homologous sequences.
In practice, our algorithm generates a solution which is at least 90% of the
optimal. Our method not only achieves performance better than or comparable to
that of a greedy algorithm, but also gives this area a mathematical foundation.
PMID- 17037964
TI - Segmenting eukaryotic genomes with the Generalized Gibbs Sampler.
AB - Eukaryotic genomes display segmental patterns of variation in various properties,
including GC content and degree of evolutionary conservation. DNA segmentation
algorithms are aimed at identifying statistically significant boundaries between
such segments. Such algorithms may provide a means of discovering new classes of
functional elements in eukaryotic genomes. This paper presents a model and an
algorithm for Bayesian DNA segmentation and considers the feasibility of using it
to segment whole eukaryotic genomes. The algorithm is tested on a range of
simulated and real DNA sequences, and the following conclusions are drawn.
Firstly, the algorithm correctly identifies non-segmented sequence, and can thus
be used to reject the null hypothesis of uniformity in the property of interest.
Secondly, estimates of the number and locations of change-points produced by the
algorithm are robust to variations in algorithm parameters and initial starting
conditions and correspond to real features in the data. Thirdly, the algorithm is
successfully used to segment human chromosome 1 according to GC content, thus
demonstrating the feasibility of Bayesian segmentation of eukaryotic genomes. The
software described in this paper is available from the author's website
(www.uq.edu.au/ approximately uqjkeith/) or upon request to the author.
PMID- 17037965
TI - Aligning families of two-dimensional gels by a combined multiresolution forward
inverse transformation approach.
AB - A new method for aligning families of two-dimensional polyacrylamide gel
electrophoresis (2D-PAGE) images arising in proteomics studies is presented.
Forward piecewise bilinear transformations are used to determine an ideal gel and
to obtain an initial alignment of the family of gels to this ideal gel. Both the
ideal landmarks and the coefficients defining the transformations are obtained by
solving a quadratic programming problem. The alignment is then improved by using
inverse transformations on finer grids. Numerical results for a family of 123
gels are reported.
PMID- 17037966
TI - Evidence-based priming.
PMID- 17037967
TI - Skin autofluorescence, a novel marker for glycemic and oxidative stress-derived
advanced glycation endproducts: an overview of current clinical studies,
evidence, and limitations.
AB - BACKGROUND: Advanced glycation endproducts (AGEs) predict long-term complications
in agerelated diseases. However, there are no clinically applicable markers for
measuring AGEs in vivo. METHODS: We have recently introduced the AGE-Reader
(DiagnOptics B.V., Groningen, The Netherlands) to noninvasively measure AGE
accumulation in the human skin of the forearm, making use of the characteristic
autofluorescence (AF) pattern that AGEs encompass. Skin AF is calculated as a
ratio of mean intensities detected from the skin between 420-600 nm and 300-420
nm. It correlates with collagen-linked fluorescence and specific skin AGE levels
from skin biopsies in diabetes, renal failure, and control subjects. Skin AF
levels are increased in patients with diabetes and renal failure and are
associated with the presence of vascular complications. Additionally, skin AF is
strongly related to the progression of coronary heart disease and mortality,
independently of traditional risk factors. Since skin pigmentation might
influence skin AF, we have investigated the relation of relative skin reflectance
(R%) to skin AF in subjects with varying skin phototypes (SPT). RESULTS: The data
presented in this article suggest that only in subjects with an SPT of V and VI
or R% <12%, no reliable measurement can be performed. Therefore, the current
prototype of the AGE-Reader is suitable for subjects with SPT I-IV or R% >12%,
and more research is needed for a broader application. CONCLUSION: The AGE-Reader
is useful as a noninvasive clinical tool for assessment of risk for long-term
vascular complications in diabetes and in other conditions associated with AGE
accumulation.
PMID- 17037968
TI - No differences in efficacy between noncultured and cultured islets in reducing
hyperglycemia in a nonvascularized islet graft model.
AB - BACKGROUND: Although islet transplantation is a promising method to restore
normoglycemia in recipients with diabetes, large numbers of pancreatic islets are
still needed. It has been suggested that the use of freshly isolated islets could
improve transplantation outcome through better vascular engraftment. Using a
technique of microencapsulation, a model where revascularization is not possible,
we investigated the importance of revascularization for transplantation outcome.
METHODS: Either 700 or 350 3-day-cultured or noncultured encapsulated islets were
transplanted intraperitoneally into syngeneic mice with alloxan-induced diabetes.
In addition, 700 nonencapsulated islets were transplanted to mice with diabetes.
Blood glucose concentrations were monitored, and glucose tolerance tests were
carried out. After 42 days, the encapsulated islets were retrieved and assayed
for glucose oxidation and insulin release rates. RESULTS: There were no
differences between capsules containing fresh or cultured islets in their
capacity to lower the blood glucose concentration of the recipients or in the in
vitro function after capsule retrieval. Interestingly, mice that were
intraperitoneally transplanted with 700 encapsulated islets had average blood
glucose levels well below 11 mM for most of the study, whereas the same number of
nonencapsulated islets had no beneficial effects on the blood glucose
homeostasis. CONCLUSIONS: Encapsulated islets can reverse hyperglycemia after
transplantation to the intraperitoneal site. This effect was not seen when
nonencapsulated islets were grafted. Since a 3- day culture period did not
influence the outcome of transplantation of encapsulated islets there is evidence
to suggest that a more appropriate revascularization may explain why freshly
isolated islets are more efficient than cultured islets.
PMID- 17037969
TI - Biocompatibility of an enzyme-based, electrochemical glucose sensor for short
term implantation in the subcutis.
AB - BACKGROUND: Continuous glucose measurements provide improved glycemic control and
may prevent hypoglycemia and long-term complications of diabetes. One of the most
promising techniques is the short-term implantation of electrochemical glucose
sensors in subcutis. However, the inflammatory reaction to these sensors may lead
to bioinstability of sensor measurements. The purpose of the present
investigation was to examine factors contributing to the observed subcutaneous
inflammatory reaction to an enzyme-based electrochemical glucose sensor for
continuous glucose measurements. The sensor biocompatibility was assessed in
vitro and in vivo. METHODS: A toxicological assessment was performed on sensor
materials and leachables, and the endotoxin content of sensors was determined by
a Limulus amoebocyte lysate (LAL) test. Moreover, as a consequence of permanent
penetration of the skin by the sensor the role of bacterial migration to the
tissue was investigated. In vivo biocompatibility was investigated through
histological examination of implanted sensor membranes for 3 days in pigs.
Additionally, the effect of needle size and type (normal vs. inserter needle) on
tissue trauma at sensor insertion was evaluated, and the healing of subcutis was
assessed histologically from 3 to 14 days after removal of sensors. RESULTS: The
toxicological assessment and the LAL test showed no concerns in a 3-day
implantation scenario, and bacterial migration to the subcutis could not be
detected. The histological examination showed that a reduction in needle size
reduced the extent of inflammation to very low levels, and that the different
sensor membranes showed similar extent and type of inflammation. Additionally,
the extent of subcutaneous tissue reaction after removal of sensors declined
gradually over time and returned to near-normal levels after 2 weeks. CONCLUSION:
The electrochemical enzyme-based glucose sensor for continuous glucose
measurements in subcutis is acceptable from a biocompatibility point of view.
Reducing the inserter needle in size reduces the trauma induced at sensor
implantation to neglible levels. Furthermore, the tissue reaction to the sensor
returns to near-normal 2 weeks after the sensor has been removed following a 3
day implantation period.
PMID- 17037970
TI - "Glucometrics"--assessing the quality of inpatient glucose management.
AB - BACKGROUND: For patients with diabetes, the quality of outpatient glycemic
control is readily assessed by hemoglobin A1c. In contrast, standardized measures
for assessing the quality of blood glucose (BG) management in hospitalized
patients are lacking. Because of recent studies demonstrating the benefits of
strict glycemic control in critically ill patients, hospitals nationwide are
dedicating resources to address this important issue. To facilitate advances in
this nascent field, standardized metrics for inpatient glycemic control should be
developed and validated. METHODS: We used 1 month of fingerstick BG levels from a
general hospital ward to develop and test three analytic models, based on three
units of inpatient BG analysis: population (i.e., ward), patient-day, and
patient. To assess the effect of the source of blood samples, we repeated these
analyses after adding venous plasma glucose levels. Finally, we employed an
idealized intensive care unit data set to establish "gold standard" metrics for
inpatient glycemic control. RESULTS: Mean and median BG levels and the proportion
of BG levels within an "optimal" range (80-139 mg/dL) were similar among the
three models, whereas hypoglycemic and hyperglycemic event rates varied
considerably. Inclusion of venous glucose levels did not substantially affect the
results. Of the three models tested, the patient-day model appears to most
faithfully reflect the quality of inpatient glycemic control. Achieving 85% of BG
levels within optimal range may be considered gold standard. CONCLUSIONS: If
validated elsewhere, these "glucometrics" would permit objective comparisons of
inpatient glycemic control among hospitals and patient care units, and would
allow institutions to gauge the success of their quality improvement initiatives.
PMID- 17037971
TI - Microdialysis-based 48-hour continuous glucose monitoring with GlucoDay: clinical
performance and patients' acceptance.
AB - BACKGROUND: This study was designed to assess clinical performance and patients'
acceptance of the minimally invasive microdialysis-based continuous glucose
monitoring system Gluco- Day() (Menarini Diagnostics, Florence, Italy) with a
targeted monitoring time of 48 h. METHODS: An inpatient sample of 28 patients
with diabetes was studied. The analysis of clinical performance was performed
using mean absolute differences (MAD) (in percent), Pearson correlations, the
Bland-Altman analysis, and Clarke Error Grid Analysis (EGA). GlucoDay glucose
values were compared with laboratory standard blood glucose measurements
(glucohexokinase assay). The patients' acceptance of the monitoring device was
assessed via two self-report scales (pain during application and discomfort while
wearing device). RESULTS: A mean (+/- SD) monitoring time of 45.7 +/- 3.3 h with
a total of 484 paired readings could be achieved. A correlation of r (average) =
0.91 and a MAD of 19.9% indicated satisfactory to good clinical performance. Of
the paired readings, 95.5% fell into the acceptable A and B zones of the EGA.
Rather wide 95% limits of agreement were revealed in the Bland-Altman analysis.
Whereas virtually no pain was experienced during sensor application, discomfort
associated with wearing the device was rather high. All of the participants,
however, stated that they would wear the device again. CONCLUSIONS: Satisfactory
to good performance of the GlucoDay monitor was observed, indicating the device
to be suitable for routine clinical use. In particular, however, the discomfort
experienced during wearing requires further improvements in its usability.
PMID- 17037973
TI - Diabetes information systems: a rapidly emerging support for diabetes
surveillance and care.
AB - BACKGROUND: With the rapid advances in information technology in the last decade,
various diabetes information systems have evolved in different parts of the
world. Availability of new technologies and information systems for monitoring
and treating diabetes is critical to achieving recommended metabolic control,
including glycosylated hemoglobin levels. The first step is to develop a
registry, including a patient identifier that can link multiple data sources,
which can then serve as a springboard to electronic mechanisms for practitioners
to gain information on performance and results. OBJECTIVE: The aim is to review
the provisions for diabetes surveillance in different parts of the world. This is
a systematic review of national and regional information systems for diabetes
surveillance. LITERATURE REVIEW: A comprehensive review was undertaken using
Medline literature review, internet search using the Google search engine, and e
mail consultation with opinion leaders. TOPICS REVIEW: National/regional-level
diabetes surveillance systems in Europe, the United States, Australia/New
Zealand, and Asia have been reviewed. State-of-the-art diabetes information
systems linking multiple data sources, with extensive audit and feedback
capabilities, have also been looked at. RESULTS: National/regional-level audit
databases have been tabulated. Diabetes information systems linking multiple data
sources have been described. Most of the developed countries have now implemented
systems such as diabetes registers and audits for diabetes surveillance in at
least some regions, if not nationally. Developing nations are beginning to
recognize the need for chronic disease management. CONCLUSIONS: With the
advancements in information technology, the diabetes registers have the potential
to rise beyond their traditional functions with dynamic data integration,
decision support, and data access, as demonstrated by some diabetes information
systems. With the rapid pace of development in electronic health records and
health information systems, countries that are beginning to build their health
information technology infrastructure could benefit from planning and funding
along these lines.
PMID- 17037972
TI - Design and implementation of a web-based patient portal linked to an ambulatory
care electronic health record: patient gateway for diabetes collaborative care.
AB - BACKGROUND: Despite the availability of expert guidelines and widespread diabetes
quality improvement efforts, care of patients with diabetes remains suboptimal.
Two key barriers to care that may be amenable to informatics-based interventions
include (1) lack of patient engagement with therapeutic care plans and (2) lack
of medication adjustment by physicians ("clinical inertia") during clinical
encounters. METHODS: The authors describe the conceptual framework, design,
implementation, and analysis plan for a diabetes patient web-portal linked
directly to the electronic health record (EHR) of a large academic medical center
via secure Internet access designed to overcome barriers to effective diabetes
care. RESULTS: Partners HealthCare System (Boston, MA), a multi-hospital health
care network comprising several thousand physicians caring for over 1 million
individual patients, has developed a comprehensive patient web-portal called
Patient Gateway that allows patients to interact directly with their EHR via
secure Internet access. Using this portal, a specific diabetes interface was
designed to maximize patient engagement by importing the patient's current
clinical data in an educational format, providing patient-tailored decision
support, and enabling the patient to author a "Diabetes Care Plan." The physician
view of the patient's Diabetes Care Plan was designed to be concise and to fit
into typical EHR clinical workflow. CONCLUSIONS: We successfully designed and
implemented a Diabetes Patient portal that allows direct interaction with our
system's EHR. We are assessing the impact of this advanced informatics tool for
collaborative diabetes care in a clinic-randomized controlled trial among 14
primary care practices within our integrated health care system.
PMID- 17037974
TI - "Waste not, want not": determining the optimal priming volume for intravenous
insulin infusions.
AB - BACKGROUND: Insulin adsorbs to plastics used for intravenous (IV) tubing. As a
result, clinical IV insulin infusion procotols advise an initial priming volume
of up to 50 mL, which may be wasteful-especially since most institutions use 100
mL IV solution bags. In this brief report, we sought to determine the optimal
priming volume required for clinical IV insulin infusions. METHODS: One hundred
units of regular human insulin was dissolved into 100 mL of 0.9% NaCl. Employing
a standard polypropylene infusion set, a priming infusion was started. At 10- mL
intervals, from 0 to 50 mL, effluent was collected directly into glass vials.
After dilution (1:10,000) using a proprietary buffer, insulin concentrations were
then measured using a double antibody radioimmunoassay. Twenty individually
prepared insulin bags were tested in this manner. RESULTS: Insulin levels without
prime were 15.8% [95% confidence interval (CI), 9.1-22.6%] lower than insulin
levels following 50 mL of prime (designated as "maximal values"). After a priming
volume of 10 mL, insulin adsorption losses fell to a marginally significant 6.6%
(95% CI, 0.1-13.1%). Following 20 mL of prime, insulin concentrations were
indistinguishable from maximal values (3.4% loss, 95% CI, -0.2% to 7.1%).
CONCLUSIONS: For standard IV insulin infusions, a priming volume of 20 mL is
sufficient to minimize the effect of insulin adsorption losses to IV lines.
Priming volumes exceeding 20 mL are wasteful, increase costs, and generate
unnecessary work for nurses and pharmacists.
PMID- 17037976
TI - The multiple endocrine neoplasia syndromes.
AB - Multiple endocrine neoplasia (MEN) type 1 and type 2 exhibit an autosomal
dominant pattern of inheritance. In the past two decades the germline mutations
that cause these inherited syndromes have been identified. The large majority of
patients with MEN1 have mutations in the menin gene. Mutations in the REarranged
during Transfection (RET) gene cause MEN2A, MEN2B, and familial medullary thyroid
carcinoma (FMTC). Specific codon mutations within RET correlate with disease
phenotype and severity. Also, children from families with MEN2A, MEN2B, or FMTC,
who are found to have inherited a mutated RET allele, can be managed by
prophylactic thyroidectomy, thus preventing the development of medullary thyroid
carcinoma (MTC), the dominant endocrinopathy in patients with these hereditary
syndromes. New insights into the molecular pathway of RET signal transduction are
leading to novel targeted therapies in patients with locally advanced or
metastatic hereditary MTC.
PMID- 17037977
TI - Stochastic simulation of chemical kinetics.
AB - Stochastic chemical kinetics describes the time evolution of a well-stirred
chemically reacting system in a way that takes into account the fact that
molecules come in whole numbers and exhibit some degree of randomness in their
dynamical behavior. Researchers are increasingly using this approach to chemical
kinetics in the analysis of cellular systems in biology, where the small
molecular populations of only a few reactant species can lead to deviations from
the predictions of the deterministic differential equations of classical chemical
kinetics. After reviewing the supporting theory of stochastic chemical kinetics,
I discuss some recent advances in methods for using that theory to make numerical
simulations. These include improvements to the exact stochastic simulation
algorithm (SSA) and the approximate explicit tau-leaping procedure, as well as
the development of two approximate strategies for simulating systems that are
dynamically stiff: implicit tau-leaping and the slow-scale SSA.
PMID- 17037978
TI - Regulation of receptor trafficking by GRKs and arrestins.
AB - To ensure that extracellular stimuli are translated into intracellular signals of
appropriate magnitude and specificity, most signaling cascades are tightly
regulated. One of the major mechanisms involved in the regulation of G protein
coupled receptors (GPCRs) involves their endocytic trafficking. GPCR endocytic
trafficking entails the targeting of receptors to discrete endocytic sites at the
plasma membrane, followed by receptor internalization and intracellular sorting.
This regulates the level of cell surface receptors, the sorting of receptors to
degradative or recycling pathways, and in some cases the specific signaling
pathways. In this chapter we discuss the mechanisms that regulate receptor
endocytic trafficking, emphasizing the role of GPCR kinases (GRKs) and arrestins
in this process.
PMID- 17037979
TI - Integration of rapid signaling events with steroid hormone receptor action in
breast and prostate cancer.
AB - Steroid hormone receptors (SRs) are ligand-activated transcription factors and
sensors for growth factor-initiated signaling pathways in hormonally regulated
tissues, such as the breast or prostate. Recent discoveries suggest that several
protein kinases are rapidly activated in response to steroid hormone binding to
cytoplasmic SRs. Induction of rapid signaling upon SR ligand binding ensures that
receptors and coregulators are appropriately phosphorylated as part of optimal
transcription complexes. Alternatively, SR-activated kinase cascades provide
additional avenues for SR-regulated gene expression independent of SR nuclear
action. We provide an overview of SR and signaling cross talk in breast and
prostate cancers, using the human progesterone receptor (PR) and androgen
receptor (AR) as models. Kinases are emerging as key mediators of SR action.
Cross talk between SR and membrane-initiated signaling events suggests a
mechanism for coordinate regulation of gene subsets by mitogenic stimuli in
hormonally responsive normal tissues; such cross talk is suspected to contribute
to cancer biology.
PMID- 17037980
TI - Hypoxia tolerance in reptiles, amphibians, and fishes: life with variable oxygen
availability.
AB - The ability of fishes, amphibians, and reptiles to survive extremes of oxygen
availability derives from a core triad of adaptations: profound metabolic
suppression, tolerance of ionic and pH disturbances, and mechanisms for avoiding
free-radical injury during reoxygenation. For long-term anoxic survival, enhanced
storage of glycogen in critical tissues is also necessary. The diversity of body
morphologies and habitats and the utilization of dormancy have resulted in a
broad array of adaptations to hypoxia in lower vertebrates. For example, the most
anoxia-tolerant vertebrates, painted turtles and crucian carp, meet the challenge
of variable oxygen in fundamentally different ways: Turtles undergo near
suspended animation, whereas carp remain active and responsive in the absence of
oxygen. Although the mechanisms of survival in both of these cases include large
stores of glycogen and drastically decreased metabolism, other mechanisms, such
as regulation of ion channels in excitable membranes, are apparently divergent.
Common themes in the regulatory adjustments to hypoxia involve control of
metabolism and ion channel conductance by protein phosphorylation. Tolerance of
decreased energy charge and accumulating anaerobic end products as well as
enhanced antioxidant defenses and regenerative capacities are also key to hypoxia
survival in lower vertebrates.
PMID- 17037981
TI - Hypoxia tolerance in mammals and birds: from the wilderness to the clinic.
AB - All mammals and birds must develop effective strategies to cope with reduced
oxygen availability. These animals achieve tolerance to acute and chronic hypoxia
by (a) reductions in metabolism, (b) the prevention of cellular injury, and (c)
the maintenance of functional integrity. Failure to meet any one of these tasks
is detrimental. Birds and mammals accomplish this triple task through a highly
coordinated, systems-level reconfiguration involving the partial shutdown of some
but not all organs. This reconfiguration is achieved through a similarly complex
reconfiguration at the cellular and molecular levels. Reconfiguration at these
various levels depends on numerous factors that include the environment, the
degree of hypoxic stress, and developmental, behavioral, and ecological
conditions. Although common molecular strategies exist, the cellular and
molecular changes in any given cell are very diverse. Some cells remain
metabolically active, whereas others shut down or rely on anaerobic metabolism.
This cellular shutdown is temporarily regulated, and during hypoxic exposure,
active cellular networks must continue to control vital functions. The challenge
for future research is to explore the cellular mechanisms and conditions that
transform an organ or a cellular network into a hypometabolic state, without loss
of functional integrity. Much can be learned in this respect from nature: Diving,
burrowing, and hibernating animals living in diverse environments are masters of
adaptation and can teach us how to deal with hypoxia, an issue of great clinical
significance.
PMID- 17037982
TI - The centaurin gamma-1 GTPase-like domain functions as an NTPase.
AB - Centaurins are a family of proteins that contain GTPase-activating protein
domains, with the gamma family members containing in addition a GTPase-like
domain. Centaurins reside mainly in the nucleus and are known to activate
phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and
vesicular trafficking. In the present study, using X-ray structural analysis,
enzymatic assays and nucleotide-binding studies, we show that, for CENTG1
(centaurin gamma-1) the GTPase-like domain has broader trinucleotide specificity.
Alterations within the G4 motif of CENTG1 from the highly conserved NKXD found in
typical GTPases to TQDR result in the loss of specificity, a lower affinity for
the nucleotides and higher turnover rates. These results indicate that the
centaurins could be more accurately classified as NTPases and point to
alternative mechanisms of cell signalling control.
PMID- 17037983
TI - Regulation of the human mucin MUC4 by taurodeoxycholic and taurochenodeoxycholic
bile acids in oesophageal cancer cells is mediated by hepatocyte nuclear factor
1alpha.
AB - MUC4 (mucin 4) is a membrane-bound mucin overexpressed in the early steps of
oesophageal carcinogenesis and implicated in tumour progression. We previously
showed that bile acids, main components of gastro-oesophageal reflux and tumour
promoters, up-regulate MUC4 expression [Mariette, Perrais, Leteurtre, Jonckheere,
Hemon, Pigny, Batra, Aubert, Triboulet and Van Seuningen (2004) Biochem. J. 377,
701-708]. HNF (hepatocyte nuclear factor) 1alpha and HNF4alpha transcription
factors are known to mediate bile acid effects, and we previously identified cis
elements for these factors in MUC4 distal promoter. Our aim was to demonstrate
that these two transcription factors were directly involved in MUC4 activation by
bile acids. MUC4, HNF1alpha and HNF4alpha expressions were evaluated by
immunohistochemistry in human oesophageal tissues. Our results indicate that
MUC4, HNF1alpha and HNF4alpha were co-expressed in oesophageal metaplastic and
adenocarcinomatous tissues. Studies at the mRNA, promoter and protein levels
indicated that HNF1alpha regulates endogenous MUC4 expression by binding to two
cognate cis-elements respectively located at -3332/-3327 and -3040/-3028 in the
distal promoter. We also showed by siRNA (small interfering RNA) approach, co
transfection and site-directed mutagenesis that HNF1alpha mediates
taurodeoxycholic and taurochenodeoxycholic bile acid activation of endogenous
MUC4 expression and transcription in a dose-dependent manner. In conclusion,
these results describe a new mechanism of regulation of MUC4 expression by bile
acids, in which HNF1alpha is a key mediator. These results bring new insights
into MUC4 up-regulation in oesophageal carcinoma associated with bile reflux.
PMID- 17037984
TI - Biosynthesis of the dystonia-associated AAA+ ATPase torsinA at the endoplasmic
reticulum.
AB - TorsinA is a widely expressed AAA(+) (ATPases associated with various cellular
activities) ATPase of unknown function. Previous studies have described torsinA
as a type II protein with a cleavable signal sequence, a single membrane spanning
domain, and its C-terminus located in the ER (endoplasmic reticulum) lumen.
However, in the present study we show that torsinA is not in fact an integral
membrane protein. Instead we find that the mature protein associates peripherally
with the ER membrane, most likely through an interaction with an integral
membrane protein. Consistent with this model, we provide evidence that the signal
peptidase complex cleaves the signal sequence of torsinA, and we show that the
region previously suggested to form a transmembrane domain is translocated into
the lumen of the ER. The finding that torsinA is a peripheral, and not an
integral membrane protein as previously thought, has important implications for
understanding the function of this novel ATPase.
PMID- 17037985
TI - An active site tyrosine residue is essential for amidohydrolase but not for
esterase activity of a class 2 histone deacetylase-like bacterial enzyme.
AB - HDACs (histone deacetylases) are considered to be among the most important
enzymes that regulate gene expression in eukaryotic cells acting through
deacetylation of epsilon-acetyl-lysine residues within the N-terminal tail of
core histones. In addition, both eukaryotic HDACs as well as their bacterial
counterparts were reported to also act on non-histone targets. However, we are
still far from a comprehensive understanding of the biological activities of this
ancient class of enzymes. In the present paper, we studied in more detail the
esterase activity of HDACs, focussing on the HDAH (histone deacetylase-like
amidohydrolase) from Bordetella/Alcaligenes strain FB188. This enzyme was
classified as a class 2 HDAC based on sequence comparison as well as functional
data. Using chromogenic and fluorogenic ester substrates we show that HDACs such
as FB188 HDAH indeed have esterase activity that is comparable with those of
known esterases. Similar results were obtained for human HDAC1, 3 and 8. Standard
HDAC inhibitors were able to block both activities with similar IC(50) values.
Interestingly, HDAC inhibitors such as suberoylanilide hydroxamic acid (SAHA)
also showed inhibitory activity against porcine liver esterase and Pseudomonas
fluorescens lipase. The esterase and the amidohydrolase activity of FB188 HDAH
both appear to have the same substrate specificity concerning the acyl moiety.
Interestingly, a Y312F mutation in the active site of HDAH obstructed
amidohydrolase activity but significantly improved esterase activity, indicating
subtle differences in the mechanism of both catalytic activities. Our results
suggest that, in principle, HDACs may have other biological roles besides acting
as protein deacetylases. Furthermore, data on HDAC inhibitors affecting known
esterases indicate that these molecules, which are currently among the most
promising drug candidates in cancer therapy, may have a broader target profile
requiring further exploration.
PMID- 17037987
TI - Psychological factors affect the frequency of belching in patients with
aerophagia.
AB - BACKGROUND: In patients with aerophagia and excessive belching an organic cause
is seldom found and a psychogenic cause is often suspected. AIM: To investigate
the effects of attention and distraction on the frequency of belching in patients
with aerophagia. METHODS: In 10 patients with aerophagia, combined esophageal
manometry and impedance monitoring was performed for 2 h, consisting of four 30
minute recording periods. Period I: patient unaware that recording had commenced.
Period II: patient informed of recording in progress. Period III: distraction by
filling in questionnaires. Period IV: no distraction. RESULTS: A total of 1,258
belches was measured, 51 of which were the result of air that escaped from the
stomach (gastric belches). A total of 1,207 belches (96%) were events during
which air was expelled in the oral direction almost immediately after entering
the esophagus from there (supragastric belches). Gastric belches were distributed
equally over the first (1.5 [0.5-2.0]), second (1.5 [0.5-2.0]), third (1.0 [0
2.0]), and fourth (1.0 [0-2.0]) recording periods. In contrast, the incidence of
supragastric belches increased significantly from 0 (0-32) in period I to 30 (18
60) in period II, after patients were told that recording was started. During
period III (questionnaires) the incidence of supragastric belches decreased to 14
(4-30). In period IV the incidence of supragastric belches increased to 21 (10
49). CONCLUSIONS: When patients with excessive belching are unaware that they are
being studied or when they are distracted, the incidence of belching is
significantly reduced. These findings underline the importance of psychological
factors and provide rationale for behavioral therapy.
PMID- 17037986
TI - Domains 16 and 17 of tropoelastin in elastic fibre formation.
AB - Naturally occurring mutations are useful in identifying domains that are
important for protein function. We studied a mutation in the elastin gene, 800
3G>C, a common disease allele for SVAS (supravalvular aortic stenosis). We showed
in primary skin fibroblasts from two different SVAS families that this mutation
causes skipping of exons 16-17 and results in a stable mRNA. Tropoelastin lacking
domains 16-17 (Delta16-17) was synthesized efficiently and secreted by
transfected retinal pigment epithelium cells, but showed the deficient deposition
into the extracellular matrix compared with normal as demonstrated by
immunofluorescent staining and desmosine assays. Solid-phase binding assays
indicated normal molecular interaction of Delta16-17 with fibrillin-1 and fibulin
5. However, self-association of Delta16-17 was diminished as shown by an elevated
coacervation temperature. Moreover, negative staining electron microscopy
confirmed that Delta16-17 was deficient in forming fibrillar polymers. Domain 16
has high homology with domain 30, which can form a beta-sheet structure
facilitating fibre formation. Taken together, we conclude that domains 16-17 are
important for self-association of tropoelastin and elastic fibre formation. This
study is the first to discover that domains of elastin play an essential role in
elastic fibre formation by facilitating homotypic interactions.
PMID- 17037988
TI - Should patients with anemia and low normal or normal serum ferritin undergo
colonoscopy?
AB - BACKGROUND: Patients with unexplained iron deficiency anemia have a greater
prevalence of colonic neoplasia, and should be evaluated for a colonoscopy. The
approach to patients with anemia without iron deficiency remains unclear.
OBJECTIVE: To compare the prevalence of colonic neoplasia in anemic patients with
normal ferritin (>50 ng/mL), to those with ferritin < or =50 ng/mL, and nonanemic
individuals. METHODS: Patients referred for colonoscopy for anemia evaluation
were stratified into 3 groups: ferritin < or =50 ng/mL, 51-100 ng/mL, and >100
ng/mL. We compared these groups to each other, and to asymptomatic nonanemic
individuals undergoing screening colonoscopy. The prevalence of advanced colonic
neoplasia was determined for each group using existing records. RESULTS: During
the study period, 414 patients who underwent colonoscopy for anemia evaluation
and 323 nonanemic individuals who underwent colonoscopy for cancer screening met
inclusion criteria. Study subjects were mostly men. The prevalence of advanced
colonic neoplasia in subjects with ferritin 51-100 ng/mL was 7.2% (95% CI 2.4
17.9%), similar to 7.9% (95% CI 5.1-11.9%) in those with ferritin < or =50 ng/mL.
The incidence of advanced colonic neoplasia in subjects with ferritin >100 ng/mL
was 1.7% (95% CI 0.1-6.6%), similar to 1.2% (95% CI 0.4-3.3%) in the asymptomatic
nonanemic group. After adjusting for age, patients with ferritin < or =50 ng/mL
and 51-100 ng/mL were almost 5 times more likely to harbor advanced colonic
neoplasia than the other groups. The addition of other laboratory parameters did
not improve the predictive value of ferritin. CONCLUSION: A ferritin cutoff of
100 ng/mL can be used to determine the need for colonoscopy in men with anemia.
PMID- 17037989
TI - Biliary manifestation of Erdheim-Chester disease mimicking Klatskin's carcinoma.
AB - Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis,
characterized by infiltration of foamy, lipid-laden histiocytes often affecting
the lower extremities and resulting in symmetrical osteosclerosis. Internal
organs involved include the lung and the kidneys, reflecting progressive
disseminated granulomatous infiltration. Progression may be fatal, especially in
cases of systemic extraosseous involvement. Here, we report a patient with
elevated serum levels of liver enzymes due to intra- and extrahepatic bile duct
stenoses. The patient's past medical history was remarkable for ECD, since 1 yr
before he had undergone surgery for a pituitary lesion in our neurosurgical
department revealing the typical histological and immunohistochemical criteria of
ECD. Because no biliary manifestation of ECD had been described so far in the
literature, surgery of suspected bile duct carcinoma was performed unraveling an
unresectable tumor of the hilar region. Surprisingly, histologic examination of
intraoperative biopsy specimens failed to demonstrate malignancy but rather
revealed another xanthogranulomatous lesion embedded in extended periductal
fibrosis as is typically described in extrahepatic parenchymal organ
manifestation of ECD. Other possible reasons for cholestatic liver disease were
excluded. Secondary cholestasis was overcome by endoscopic dilatation and biliary
stenting with stents being exchanged every 3 months. During follow-up for 7 yr we
have observed only a slight increase of the hilar stenosis so far. This is the
first report describing biliary manifestation of ECD. Even though ECD is a rare
cause of cholestasis, it should be considered in patients with this disorder in
the setting of multiorgan manifestation.
PMID- 17037990
TI - Familial aggregation in constipated subjects in a tertiary referral center.
AB - OBJECTIVES: Clinical observation showed that there is family aggregation in
constipated subjects, but formal data are lacking. This prompted us to conduct a
formal family study in constipated subjects. METHODS: Constipated subjects
(probands) were identified according to the Rome II and Chinese constipation
questionnaire criteria, healthy subjects were chosen as controls. Living first
degree relatives (parents, siblings, and children) and spouses (as internal
controls) from both groups were identified. The questionnaire on Rome II criteria
was given to the relatives either through the index subjects or by mail. The
questionnaire was received by mailing back or through the index subjects. Any
nonresponders were chased. RESULTS: There were 132 probands with constipation and
114 controls. The Rome II questionnaire was sent to a total of 677 relatives of
the probands and 591 of the controls. Relatives were comparable in mean age, sex
distribution, family size, and marital status in the two groups. Constipation
prevalence was 16.4% in probands' relatives versus 9.1% in controls' relatives,
i.e., 13% in the relatives from both proband and controls. Among the constipated
relatives, 6.3%versus 9.3% of the relatives were spouses of the probands and
controls (P = 0.5). Subjects with more family members having constipation will
have higher risk of constipation: OR 2.02, CI 1.14-3.65, P = 0.0177 for at least
one family member; OR 3.99, CI 1.86-9.23, P = 0.0006 for at least two family
members. CONCLUSIONS: Familial aggregation of constipation occurs, supporting a
genetic or intrafamilial environment component.
PMID- 17037991
TI - Acute appendicitis due to appendiceal obstruction from a migrated biliary stent.
AB - Endoscopic plastic biliary stenting is a common procedure in the management of
benign biliary pathology. Complications from biliary stenting are rare, with
stent occlusion being the most common. Another late complication of long-term
biliary stenting is stent migration, which occasionally can result in bowel
perforation and obstruction. We report an extremely unusual complication of acute
appendicitis due to appendiceal orifice obstruction from a migrated biliary
stent. The condition was suspected from the history in association with the
radiological findings and was successfully treated nonoperatively with endoscopic
stent removal.
PMID- 17037992
TI - Incidence of arterial injuries detected by arteriography following percutaneous
right-lobe ultrasound-guided core liver biopsies in human subjects.
AB - PURPOSE: To determine the incidence and significance of arterial injuries
detected by angiography subsequent to ultrasound-guided random core liver
biopsies in normal healthy adults. MATERIALS AND METHODS: Retrospective analysis
of 55 potential living related liver donors who underwent an ultrasound-guided
random liver biopsy and a visceral angiogram was performed (January, 1999 to May,
2002). All liver biopsy samples (obtained by 2-3 18-gauge needle passes) were re
evaluated prospectively by a transplant pathologist for adequacy (defined: >or=5
complete portal triads). Subjects who underwent angiograms before the biopsy or
>7 days after the biopsy were excluded from the arterial injury evaluation.
Angiograms were reviewed by two angiographers. Arterial injuries were identified
and classified by consensus into contusions, active bleeding, arterial-venous
fistulae, and pseudoaneurysms. RESULTS: Mean needle pass was 2.1. No major
complications were encountered. All samples were deemed pathologically adequate.
Forty-eight potential donors were included for the arterial injury evaluation.
Three arterial injuries (two arterioportal fistulae, 4.2%) were found in 48
angiograms (6.3%). None of the three injuries required intervention. CONCLUSION:
The incidence of arterioportal fistulae following core liver biopsies has not
changed over the past three decades despite improvement in biopsy needle
technology, reduction of needle caliber, and the use of image guidance.
PMID- 17037993
TI - Characterization, outcome, and prognosis in 273 patients with primary sclerosing
cholangitis: A single center study.
AB - OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver
disease with varying severity and progression. This study describes the natural
history of PSC patients and evaluates the prognostic significance of clinical,
biochemical, and cholangiographic findings constructing a novel prognostic model.
METHODS: A population of 273 German PSC patients was studied with a median follow
up time of 76 months (range 1-280 months). Survival curves were analyzed by the
Kaplan-Meier method, and prognostic significance of clinical, biochemical, and
cholangiographic features recorded at the time of diagnosis was evaluated by
multivariate analysis using Cox proportional-hazards regression models. RESULTS:
The estimated median survival from the time of diagnosis to death or time of
liver transplantation was 9.6 yr. One hundred eight (39.6%) patients underwent
liver transplantation. Hepatobiliary malignancies were found in 39 (14.3%)
patients of the entire PSC population. Age, low albumin, persistent bilirubin
elevation longer than 3 months, hepatomegaly, splenomegaly, dominant bile duct
stenosis, and intra- and extrahepatic ductal changes at the time of diagnosis
were found to be independent risk factors correlating with poor prognosis and
were used to construct a new prognostic model. CONCLUSIONS: A persistent
bilirubin elevation for longer than 3 months from the time of diagnosis could be
identified as a novel marker correlating with a poor outcome. A new prognostic
model was developed to predict progression of PSC, which may be useful in timing
of liver transplantation.
PMID- 17037994
TI - Survival after colorectal cancer in patients with Crohn's disease: A nationwide
population-based Danish follow-up study.
AB - BACKGROUND AND AIMS: Patients with Crohn's disease (CD) are at increased risk of
colorectal cancer (CRC), but little is known about the impact of CD on CRC
prognosis. Based on nationwide population-based registries, we compared survival
among CRC patients with CD and CRC patients without CD. METHODS: We used the
Danish Cancer Registry and the Danish Hospital Discharge Registry to identify all
patients diagnosed with CRC, with and without CD, in Denmark between 1977 and
1999. We ascertained the stage distribution at the time of CRC diagnosis and 1-
and 5-yr survival both for patients with Crohn-associated CRC and patients with
non-Crohn CRC. Cox regression was used to compute hazard ratios (HRs), adjusting
for gender, age, calendar year, and stage. RESULTS: We identified 100 CRC
patients with CD and 71,438 CRC patients without CD. At the time of diagnosis,
patients with CD were younger, but stage distributions were similar in the two
groups. The overall HR for CRC with CD compared to CRC without CD was 1.82 (95%
CI 1.36-2.43) after 1 yr of follow-up, and 1.57 (95% CI 1.24-1.99) after 5 yr of
follow-up. Subanalyses showed that the effect of CD on CRC survival was more
pronounced in the youngest patients (0-59 yr), in men, and in patients whose
tumors had regional spread. CONCLUSIONS: We found that CD worsens the prognosis
of CRC, particularly CRC with regional spread.
PMID- 17037995
TI - Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a
meta-analysis of randomized controlled trials.
AB - OBJECTIVE: The role of proton pump inhibitors (PPIs) in suspected GERD-related
chronic laryngitis (CL) is controversial. Hence, we performed a meta-analysis of
the existing randomized controlled trials (RCTs) to evaluate the efficacy of PPIs
in this disorder. METHODS: Data extracted from MEDLINE (1966 to August 2005),
Cochrane Controlled Trials Register (1997 to August 2005), EMBASE (1980 to August
2005), ClinicalTrials.gov website, and meetings presentations (1999-2005).
Published and unpublished randomized placebo-controlled trials of PPIs in
suspected GERD-related CL were selected by consensus. Random effects model was
utilized with standard approaches to quality assessment, sensitivity analysis,
and an exploration of heterogeneity and publication bias. The primary outcome
measure was defined as the proportion of patients with >or=50% reduction in self
reported laryngeal symptoms. RESULTS: Pooled data from 8 studies (N = 344, PPI
195, placebo 149; mean age 51 yr; males 55%; study duration 8-16 wk) were
analyzed. No significant quantitative heterogeneity was found among the studies
(chi2= 11.22, P= 0.13). Overall, PPI therapy resulted in a nonsignificant symptom
reduction compared to placebo (relative risk 1.28, 95% confidence interval 0.94
1.74). No clinical predictors of PPI response were identified on meta-regression
analysis done at study level. CONCLUSIONS: PPI therapy may offer a modest, but
nonsignificant, clinical benefit over placebo in suspected GERD-related CL.
Validated diagnostic guidelines may facilitate the recognition of those patients
most likely to respond favorably to PPI treatment.
PMID- 17037996
TI - Autoimmune hemolytic anemia in patients with liver transplants for primary
biliary cirrhosis: Three case reports and a review of the literature.
AB - BACKGROUND: Hemolytic anemia is rare after liver transplant and is usually
associated with ABO mistmatch, post-transplant lymphoproliferative disorders, or
medications. CASE REPORTS: We report three patients who had undergone successful
liver transplants for primary biliary cirrhosis (PBC) and developed direct
antibody test positive autoimmune hemolytic anemia (AIHA) several years into
uncomplicated post-transplant management. For two of the patients, the hemolysis
responded to steroids and rituximab. One patient required a surgical splenectomy.
DISCUSSION: AIHA is an immune-mediated hemolysis that has been reported in
patients with PBC. There are no reports of AIHA in patients following liver
transplantation for this disease. AIHA should be considered in stable PBC
patients who develop anemia years after liver transplant.
PMID- 17037999
TI - The art of reading sequence electropherograms.
PMID- 17038000
TI - Interrelationship and familiality of dyslexia related quantitative measures.
AB - Dyslexia is a complex gene-environment disorder with poorly understood etiology
that affects about 5% of school-age children. Dyslexia occurs in all languages
and is associated with a high level of social and psychological morbidity for the
individual and their family; approximately 40-50% have persistent disability into
adulthood. The core symptoms are word reading and spelling deficits, but several
other cognitive components influence the core phenotype. A broad spectrum of
dyslexia related phenotypes, including phonological decoding, phoneme awareness,
orthographic processing, short-term memory, rapid naming and basic mathematical
abilities, were investigated in large sample of 287 German dyslexia families. We
explored the interrelationship between the component phenotypes using correlation
and principal component analyses (PCA). In addition, we estimated familiality for
phenotypes as well as for the factors suggested by PCA. The correlation between
the component phenotypes varied between -0.1 and 0.7. The PCA resulted in three
factors: a general dyslexia factor, a speed of processing factor and a
mathematical abilities factor. The familiality estimates of single components and
factors ranged between 0.25 and 0.63. Instead of analyzing single dyslexia
related components, multivariate analyses including factor analytic approaches
may help in the identification of susceptibility genes.
PMID- 17038001
TI - Preceding immunosuppressive therapy with antithymocyte globulin and ciclosporin
increases the incidence of graft rejection in children with aplastic anaemia who
underwent allogeneic bone marrow transplantation from HLA-identical siblings.
AB - The incidence of graft rejection was determined in 66 children with acquired
aplastic anaemia (AA) following bone marrow transplantation (BMT) from a related
donor. Eleven of 65 evaluable patients experienced either early or late
rejection. Multivariate analysis identified previous immunosuppressive therapy
with antithymocyte-globulin (ATG) and ciclosporin (CsA) as a risk factor for
graft rejection (relative risk: 16.6, P = 0.001). Patients who received ATG and
CsA had a significantly lower probability of failure-free survival than those who
did not (69.7 +/- 6.2% vs. 87.9 +/- 8.0%, P = 0.044). These results suggest that
BMT should be instituted immediately in children with severe AA who have human
leucocyte antigen-identical siblings.
PMID- 17038002
TI - Benefit sharing: from obscurity to common knowledge.
PMID- 17038003
TI - Women in developing countries and benefit sharing.
AB - The aim of this paper is to show that any process of benefit sharing that does
not guarantee the representation and participation of women in the decision
making process, as well as in the distribution of benefits, contravenes a central
demand of social justice. It is argued that women, particularly in developing
countries, can be excluded from benefits derived from genetic research because of
existing social structures that promote and maintain discrimination. The paper
describes how the structural problem of gender-based inequity can impact on
benefit sharing processes. At the same time, examples are given of poor women's
ability to organise themselves and to achieve social benefits for entire
communities. Relevant international guidelines (e.g. the Convention on
Biodiversity) recognise the importance of women's contributions to the protection
of biodiversity and thereby, implicitly, their right to a share of the benefits,
but no mechanism is outlined on how to bring this about. The authors make a clear
recommendation to ensure women's participation in benefit sharing negotiations by
demanding seats at the negotiation table.
PMID- 17038004
TI - North-South benefit sharing arrangements in bioprospecting and genetic research:
a critical ethical and legal analysis.
AB - Most pharmaceutical research carried out today is focused on the treatment and
management of the lifestyle diseases of the developed world. Diseases that affect
mainly poor people are neglected in research advancements in treatment because
they cannot generate large financial returns on research and development costs.
Benefit sharing arrangements for the use of indigenous resources and genetic
research could only marginally address this gap in research and development in
diseases that affect the poor. Benefit sharing as a strategy is conceptually
problematic, even if one, as we do, agrees that impoverished indigenous
communities should not be exploited and that they should be assisted in improving
their living conditions. The accepted concept of intellectual property protection
envisages clearly defined originators and owners of knowledge, whereas the
concept of community membership is fluid and indigenous knowledge is, by its very
nature, open, with the originator(s) lost in the mists of time. The delineation
of 'community' presents serious conceptual and practical difficulties as few
communities form discrete, easily discernable groups, and most have problematic
leadership structures. Benefit sharing is no substitute for governments'
responsibility to uplift impoverished communities. Benefit sharing arrangements
may be fraught with difficulties but considerations of respect and equity demand
that prior informed consent and consultation around commercialisation of
knowledge take place with the source community and their government.
PMID- 17038005
TI - Sharing the benefits of genetic resources: from biodiversity to human genetics.
AB - Benefit sharing aims to achieve an equitable exchange between the granting of
access to a genetic resource and the provision of compensation. The Convention on
Biological Diversity (CBD), adopted at the 1992 Earth Summit in Rio de Janeiro,
is the only international legal instrument setting out obligations for sharing
the benefits derived from the use of biodiversity. The CBD excludes human genetic
resources from its scope, however, this article considers whether it should be
expanded to include those resources, so as to enable research subjects to claim a
share of the benefits to be negotiated on a case-by-case basis. Our conclusion on
this question is: 'No, the CBD should not be expanded to include human genetic
resources.' There are essential differences between human and non-human genetic
resources, and, in the context of research on humans, an essentially fair
exchange model is already available between the health care industry and research
subjects. Those who contribute to research should receive benefits in the form of
accessible new health care products and services, suitable for local health needs
and linked to economic prosperity (e.g. jobs). When this exchange model does not
apply, as is often the case in developing countries, individually negotiated
benefit sharing agreements between researchers and research subjects should not
be used as 'window dressing'. Instead, national governments should focus their
finances on the best economic investment they could make; the investment in
population health and health research as outlined by the World Health
Organization's Commission on Macroeconomics and Health; whilst international
barriers to such spending need to be removed.
PMID- 17038006
TI - Vicissitudes of benefit sharing of crop genetic resources: downstream and
upstream.
AB - In this article, we will first give a historic overview of the concept of benefit
sharing and its appearance in official agreements, particularly with respect to
crop genetic resources. It will become clear that, at present, benefit sharing is
primarily considered as an instrument of compensation or exchange, and thus
refers to commutative justice. However, we believe that such a narrow
interpretation of benefit sharing disregards, and even undermines, much of its
(historical) content and potency, especially where crop genetic resources are
concerned. We argue that benefit sharing should not be based merely on
commutative justice but rather on a broader model that is also grounded in the
concept of distributive justice. This has repercussions for the application of
benefit sharing, which we try to clarify by distinguishing between downstream and
upstream benefit sharing. Upstream benefit sharing is not so much inspired by
compensation for actions done, or the distribution downstream of benefits
developed, but by the idea of shared decision-making on the research and
development of resources fundamental to human welfare. Going upstream in the
research process of crop genetic resources, and determining research agendas and
improving crops according to the needs of the poor, benefit sharing may well be a
tool to contribute to world food security and global justice. We concretize our
ideas on upstream benefit sharing by introducing a set of criteria that determine
the success of consultations on agricultural research agenda setting.
PMID- 17038007
TI - Biodiversity, biopiracy and benefits: what allegations of biopiracy tell us about
intellectual property.
AB - This paper examines the concept of biopiracy, which initially emerged to
challenge various aspects of the regime for intellectual property rights (IPR) in
living organisms, as well as related aspects pertaining to the ownership and
apportioning of benefits from 'genetic resources' derived from the world's
biodiversity. This paper proposes that we take the allegation of biopiracy
seriously due to the impact it has as an intervention which indexes a number of
different, yet interrelated, problematizations of biodiversity, biotechnology and
IPR. Using the neem tree case as an example, it describes activists' use of the
term as one that involves a deliberate simplification of science and IPR.
Additionally, it argues that in so doing, biopiracy is positioned as a touchstone
that mobilizes actors and problems, and ultimately generates 'solutions' to the
very challenges it creates. The paper will also encourage a view of biopiracy
claims that does not always treat them simply as claims of theft, or as a
misallocation of benefits, but rather as claims that are designed to raise
broader questions about the IPR system itself. It concludes by advocating that,
in order to properly understand how to address biopiracy, we must be prepared to
move beyond the current narrow readings to develop a more complete picture of the
term's influence in challenging how, and by whom, the decisions about what is
natural and what is invented come to be made.
PMID- 17038009
TI - 'Schools without walls?' Developments and challenges in dental outreach teaching
report of a recent symposium.
AB - During the 2004 annual meeting of the International Association for Dental
Research, the Education Research Group held a symposium on dental outreach
teaching. After a brief introduction, which reviews relevant aspects of the
relatively sparse literature, this paper summarises the proceedings, the themes
and conclusions that emerged and the research issues that were identified. It
aims to describe aspects of current practice around the world and to promote
future discussion. Presenters gave details of outreach programmes for dental
undergraduates in Australia, Finland, Malaysia (and Southeast Asia), the United
Kingdom and the United States. From these presentations four themes emerged. They
were: reasons for the introduction of outreach teaching, its perceived beneficial
effects, organisational issues, educational issues. The reasons included a
recognition of the need to educate dental undergraduates as members of 'care
teams' in the environments and communities where they were ultimately like to
work and the current shortage of both suitable patients and teachers (faculty) in
many dental schools. A wide range of potential benefits and some disadvantages
were identified. The organisational issues were, in the main, seen to relate to
finance and administration. The educational issues included the need to train and
monitor the performance of teachers at outreach clinics and to assess the
performance of the undergraduates whilst at the outreach locations. It was
concluded that new technology made it easier to teach at a distance and it was
possible to create a dental 'school without walls'. It was recognised that few
evaluations of dental outreach teaching have been carried out and that there were
many research questions to be answered, including: whether it should be a
voluntary or compulsory part of the undergraduate curriculum, how long it should
last and what type of outcomes should be assessed.
PMID- 17038010
TI - The oral ecosystem: implications for education.
AB - We propose a model that is applicable to oral health education. The model
describes the oral cavity in a complexity-based ecological context. This concept
includes the premise that factors from different organisational levels
(biological, individual, community, society) interact in a complex way with the
potential to 'stress' the ecosystem and thereby provoke changes. This mode of
action complies with the understanding of the oral cavity as a complex adaptive
system. An ecological model is actively used in the undergraduate problem-based
curriculum at the Faculty of Odontology, Malmo University, Sweden and has
recently been applied as a conceptual basis for the new dental curriculum being
established at the University of Tromso in Northern Norway. The purpose is to
encourage and promote an ecological, health-oriented view and to stimulate
reflections on premises for oral health and diseases in an integrated context.
PMID- 17038011
TI - The use of articulators in UK dental schools.
AB - The increasing complexity of many restorative procedures often involves
articulation of study and working casts to ensure accurate fabrication of
restorations. Correct selection and use of articulators can be crucial to
successful restoration. The aim of this paper is to determine which articulators
are recommended for various restorative procedures in UK dental schools, for use
by undergraduate students. A questionnaire-based study of all UK dental schools
was carried out, with a 100% response rate. Recommended articulator application
for specified procedures was established from the literature and questionnaire
results were compared with this. The results indicated that dental schools in the
UK generally teach appropriate articulator use for most procedures. However,
there are some limited areas of what may be argued to be inappropriate
recommendation in some establishments.
PMID- 17038012
TI - Difficulties encountered at the beginning of professional life: results of a 2003
pilot survey among undergraduate students in Paris Rene Descartes University
(France).
AB - In addition to dental hospital clinical activity, dental students at Paris Rene
Descartes University have the opportunity in their final year of study to
practise clinically in a dental office, as associates. This paper outlines a
pilot, experimental study designed to assess student reaction to this Vocational
Clinical Activity (VCA) in order to identify relevant weaknesses of the
undergraduate programme. Using questionnaires, data were collected for each of
the following clinical or management skills: clinical difficulty, therapeutic
decision-making, patient/practitioner relationship, time management,
administrative matters and technical problems. Students were asked to rank each
item in order of difficulty (1, high level to 6, low level). A high response rate
was observed (90%) among the 50 undergraduate VCA students. The results pointed
out three main difficulties encountered by undergraduate students during the VCA:
time management (90% of the students), administrative matters (85% of the
students) and clinical decision-making (80% of the students). These preliminary
results need further investigation. However, they give us the incentive to carry
on with this type of assessment and to extend it to young, qualified colleagues'
perceptions and to other French Universities.
PMID- 17038013
TI - A survey on the preference for continuing professional dental education amongst
general dental practitioners who attended the 26th Asia Pacific Dental Congress.
AB - AIMS: To identify the subjects of interest and to examine the modes as well as
means of study for continuing professional dental education amongst general
dental practitioners who attended the 26th Asia Pacific Dental Congress, 28 May-1
June 2004, Hong Kong. METHODS: A total of 381 general dental practitioners as the
registered conference delegates from Hong Kong, Mainland China and other Asia
Pacific regions were randomly selected for the present survey. The survey was
conducted through face-to-face interviews by a group of practising dentists in
Hong Kong. RESULTS: Overall, orthodontics and prosthodontics were the most
popular subjects for clinical degree programmes, whilst oral implantology and
cosmetic dentistry were the highly preferred subjects for continuing education
courses. Concerning the preferred mode of study for degree programmes, the part
time study mode was chosen by 68.3% of the participating dentists. A didactic
teaching approach was preferred by most of the participants (81.7%) for
postgraduate study. The majority of the interviewees (76.5%) were interested in a
proposed clinical degree programme to be offered jointly by The University of
Hong Kong and a leading university in the Mainland. Overall, there was no marked
difference in the preference for continuing dental education amongst the
respondents from Hong Kong, Mainland China and other Asia-Pacific regions.
CONCLUSIONS: The present survey shows the currently preferred specialty areas and
subjects for continuing professional dental education amongst the general dental
practitioners who attended the 26th Asia Pacific Dental Congress, with didactic
teaching as the most preferred mode of study on a part-time basis.
PMID- 17038014
TI - Tutor perceptions of the use of a reflective portfolio within a pastoral tutor
system to facilitate undergraduate personal development planning.
AB - All Higher Education Institutions in the UK are now required to provide
transcripts of student activity and outcomes of summative assessments. In
addition, the student should be able to reflect on their learning and plan their
own development. This article reports on the staff evaluation of the use of a
reflective portfolio facilitating the production of highly individualised
personal development plans within an existing tutor system. A number of
significant issues are highlighted; tutor systems adopting this approach must
maintain flexibility for managing student crises when they arise, the difference
between appraisal and assessment needs clear definition for both students and
tutors, training in basic mentoring skills should be provided for all tutors,
tutors should be aware of the difficulties many students experience with
reflection and also be alert to the over reflective learner.
PMID- 17038015
TI - Implementing an Objective Structured Clinical Examination (OSCE) in dental
education: effects on students' learning strategies.
AB - OBJECTIVES: To investigate the effect of an Objective Structured Clinical
Examination (OSCE) on dental students' learning strategies and competence to
manage periodontal diseases in patients. The implemented OSCE was expected to be
superior to the existing Written Exam in fostering the acquisition of clinical
competencies in terms of study strategies that are more oriented towards clinical
practice, longer study time, greater clinical proficiency, and more realistic
self-assessment. MATERIAL AND METHODS: After a clinical course in periodontology,
72 third year dental students were assessed summatively, either using a Written
Exam or an OSCE (P-OSCE). The students were informed beforehand about the
assessment formats. The self-assessed clinical competence, study time and
strategies (i.e. practice with a manikin, peers and patient case) were evaluated
by means of a questionnaire. After a comprehensive dental care course, all 72
students were assessed by an overall end-of-year OSCE, in which three periodontal
stations were included 'measuring pockets', 'educating patients' and 'tracing an
X-ray with bone-loss'. The competence of the previous Written Exam group and the
P-OSCE group was investigated by determining the mean scores and pass-fail scores
of three periodontal test-stations as well as the total score of the end-of-year
OSCE. The degree of realistic self-assessment was studied by correlating the self
assessed competencies as evaluated by means of the questionnaire with the total
score of the end-of-year OSCE. RESULTS: Self-assessed clinical competence, study
time and study strategies showed no differences between the P-OSCE and the
Written Exam-group. The clinical competence determined in the test-station
'measuring pockets' in the end of year overall OSCE was higher for the P-OSCE
group (P = 0.05) when compared with the Written Exam group; the two groups
performed equally well in the test station 'educating patients', whereas the
performance in 'tracing an X-ray with bone-loss' was better in the Written Exam
group. This group also had a higher total score in the end-of-year OSCE (P =
0.05). The degree of realistic self-assessment was higher in the P-OSCE group
than in the Written Exam group: in the P-OSCE group the self-assessed clinical
competencies correlated significantly with the total score of the overall end-of
year OSCE (P < or = 0.05). CONCLUSIONS: No effects of the implementation of an
OSCE in undergraduate periodontal education were observed in study strategies,
but the implementation of an OSCE in undergraduate periodontal education appears
to stimulate learning, resulting in greater achievement of specific clinical
competence and a greater level of realistic self-assessment.
PMID- 17038016
TI - Reasons for choosing dentistry as a career: a study involving male and female
first-year students in Peru.
AB - The aim of this study was to compare the reported reasons to choose dentistry as
a career between Peruvian male and female first-year students. A self-completion
questionnaire was administered to 75 first-year students registered at the
Faculty of Dentistry of the Universidad Peruana Cayetano Heredia, Lima, Peru. The
questionnaire comprised 16 items grouped into four categories (economic,
professional, vocational and personal background). Students rated the importance
of each item for selecting dentistry as a career on a Likert-type scale of five
points. The Mann-Whitney test was used to compare groups and item scores by
gender. A male/female proportion of 1/2.1 was found in the pool of participating
students. When group and item scores were compared between genders, statistically
significant differences were only found for vocational and personal background
reasons (P < 0.05); however, the three reasons that obtained higher scores for
each gender were found to be different. It is recommended that further studies be
conducted to increase the sample, by extending the study and evaluating not only
reasons for choosing dentistry, but also other factors that may influence the
decision.
PMID- 17038017
TI - Sickle cell disease due to compound heterozygosity for Hb S and a novel 7.7-kb
beta-globin gene deletion.
AB - A young woman originally from Cape Verde islands presented with mild sickle cell
disease. Her blood counts and hemoglobin analysis results initially suggested
that she might be either homozygous for the sickle cell hemoglobin (Hb S) with
concomitant alpha-thalassemia, or compound heterozygous for Hb S and beta0
thalassemia, deletional deltabeta-thalassemia or hereditary persistence of fetal
hemoglobin (HPFH). We utilized a novel polymerase chain reaction (PCR)-based
screening technique and found a hitherto unrecognized 7.7-kb deletion, starting
from the HBB IVSII to 3' downstream of the beta-globin gene. This diagnostic
approach can be applied to decipher other similar deletional mutations. This is
the second known deletion that removes the 3'-end but preserves the integrity of
the 5'-end of the beta-globin gene. Furthermore, the identification of the
deletion allows proper genetic counseling for affected families.
PMID- 17038018
TI - Correlation of echocardiography parameters with cardiac magnetic resonance
imaging in transfusion-dependent thalassaemia major.
AB - BACKGROUND AND OBJECTIVE: Heart iron load (cardiac Fe) can be indirectly
quantified by cardiac magnetic resonance (CMR) T2*. CMR accessibility is limited,
whereas echocardiography (Echo) is relatively inexpensive and readily available.
The objective was to find Echo parameters that may be useful for predicting
cardiac Fe. DESIGN AND METHODS: We compared a number of parameters derived from
Echo to cardiac Fe in 142 thalassaemia major patients who had undergone a CMR
study. RESULTS: All patients with decreased left ventricular (LV) function had
cardiac Fe. After removing those patients from the analysis, the total diameter
index (Tdi) >5.57 cms/m2, left atrial diameter index >2.41 cm/m2, and the
diastolic parameter E/A > 1.96 were highly specific (91.4%, 97.1% and 96.9%
respectively) but had low sensitivity (31.8%, 20.45% and 21.8%) in predicting
iron load. A right ventricular index >1.47 cm/m2, LV systolic index >2.26 cm/m2
or Tdi >6.26 cm/m2 discriminated between patients with no, or mild to moderate
cardiac Fe from those with heavy load, with specificity of 91%, 98.5%, and 98.5%,
respectively, but with low sensitivity. INTERPRETATION AND CONCLUSIONS: Echo
parameters for cardiac Fe prediction have restricted value, whereas CMR is
essential to assess cardiac Fe. However, patients with decreased LV systolic
function should be considered a priori as having cardiac Fe, and chelation
therapy should be intensified. This also applies to patients who have the above
described Echo criterion values, even if CMR is not available. Once a patient is
found by CMR to have cardiac Fe, then the above Echo criterion values may be
useful for ongoing monitoring.
PMID- 17038019
TI - Serum calcium is an independent predictor of quality of life in multiple myeloma.
AB - Bone disease is an important feature of multiple myeloma, and hypercalcaemia is a
frequent complication of this disease. We examined the association between serum
calcium and quality of life (QOL) scores of 686 multiple myeloma patients at the
time of diagnosis. Data from two Nordic studies using the EORTC QLQ-C30
questionnaire were analysed by means of linear regression analysis and a curve
fitting program. Serum calcium was independently related to appetite loss,
nausea/vomiting and physical functioning (P < 0.001) and to cognitive functioning
(P = 0.001), i.e. scores reflecting symptoms that are well known in non-malignant
hypercalcaemia. In addition, we found a highly significant independent
relationship between serum calcium and the scores for fatigue and pain (P <
0.001). Serum calcium appeared to be as strong a predictor for fatigue as the
concentration of haemoglobin. A cubic model (y = a + bx3) fitted the data
slightly better than the simple linear model (y = a + bx) and suggested worsening
QOL scores at levels of serum calcium above 2.5-3.0 mmol/L. Hypercalcaemia in
patients with multiple myeloma seems to be associated with the same symptoms as
in non-malignant hypercalcaemia. In addition, an increased level of serum calcium
may aggravate the pain and fatigue caused by the skeletal disease itself.
PMID- 17038020
TI - The importance of EEG and variability of MRI findings in acute hemorrhagic
leukoencephalitis.
PMID- 17038021
TI - Patient with adult-onset congenital neuromuscular disease with uniform type 1
fibers.
PMID- 17038027
TI - Epstein-Barr virus-associated primary leptomeningeal lymphoma.
PMID- 17038028
TI - Cost of disorders of the brain in Europe.
PMID- 17038029
TI - Rhabdomyolysis associated with hyponatremia and adrenal insufficiency.
PMID- 17038030
TI - EFNS guidelines on pharmacological treatment of neuropathic pain.
AB - Neuropathic pain treatment remains unsatisfactory despite a substantial increase
in the number of trials. This EFNS Task Force aimed at evaluating the existing
evidence about the pharmacological treatment of neuropathic pain. Studies were
identified using first the Cochrane Database then Medline. Trials were classified
according to the aetiological condition. All class I and II controlled trials
(according to EFNS classification of evidence) were assessed, but lower-class
studies were considered in conditions that had no top level studies. Only
treatments feasible in an outpatient setting were evaluated. Effects on pain
symptoms/signs, quality of life and comorbidities were particularly searched for.
Most of the randomized controlled trials included patients with postherpetic
neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes.
These trials provide level A evidence for the efficacy of tricyclic
antidepressants, gabapentin, pregabalin and opioids, with a large number of class
I trials, followed by topical lidocaine (in PHN) and the newer antidepressants
venlafaxine and duloxetine (in PPN). A small number of controlled trials were
performed in central pain, trigeminal neuralgia, other peripheral neuropathic
pain states and multiple-aetiology neuropathic pains. The main peripheral pain
conditions respond similarly well to tricyclic antidepressants, gabapentin, and
pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more
refractory. There are too few studies on central pain, combination therapy, and
head-to-head comparison. For future trials, we recommend to assess quality of
life and pain symptoms or signs with standardized tools.
PMID- 17038031
TI - Review of the therapeutic management of Parkinson's disease. Report of a joint
task force of the European Federation of Neurological Societies and the Movement
Disorder Society-European Section. Part I: early (uncomplicated) Parkinson's
disease.
AB - The aim of the study was to provide evidence-based recommendations for the
management of early (uncomplicated) Parkinson's disease (PD), based on a review
of the literature. Uncomplicated PD refers to patients suffering from the
classical motor syndrome of PD only, without treatment-induced motor
complications and without neuropsychiatric or autonomic problems. MEDLINE,
Cochrane Library and International Network of Agencies for Health Technology
Assessment (INAHTA) database literature searches were conducted. National
guidelines were requested from all European Federation of Neurological Societies
(EFNS) societies. Non-European guidelines were searched for using MEDLINE. Part I
of the guidelines deals with prevention of disease progression, symptomatic
treatment of motor features (parkinsonism), and prevention of motor and
neuropsychiatric complications of therapy. For each topic, a list of therapeutic
interventions is provided, including classification of evidence. Following this,
recommendations for management are given, alongside ratings of efficacy.
Classifications of evidence and ratings of efficacy are made according to EFNS
guidance. In cases where there is insufficient scientific evidence, a consensus
statement (good practice point) is made.
PMID- 17038032
TI - Review of the therapeutic management of Parkinson's disease. Report of a joint
task force of the European Federation of Neurological Societies (EFNS) and the
Movement Disorder Society-European Section (MDS-ES). Part II: late (complicated)
Parkinson's disease.
AB - To provide evidence-based recommendations for the management of late
(complicated) Parkinson's disease (PD), based on a review of the literature.
Complicated PD refers to patients suffering from the classical motor syndrome of
PD along with other motor or non-motor complications, either disease-related
(e.g. freezing) or treatment-related (e.g. dyskinesias or hallucinations).
MEDLINE, Cochrane Library and INAHTA database literature searches were conducted.
National guidelines were requested from all EFNS societies. Non-European
guidelines were searched for using MEDLINE. Part II of the guidelines deals with
treatment of motor and neuropsychiatric complications and autonomic disturbances.
For each topic, a list of therapeutic interventions is provided, including
classification of evidence. Following this, recommendations for management are
given, alongside ratings of efficacy. Classifications of evidence and ratings of
efficacy are made according to EFNS guidance. In cases where there is
insufficient scientific evidence, a consensus statement ('good practice point')
is made.
PMID- 17038033
TI - Critical illness polyneuropathy and myopathy: clinical features, risk factors and
prognosis.
AB - Acquired neuromuscular weakness due to critical illness polyneuropathy and
myopathy (CIPNM) frequently develops in patients hospitalized in the intensive
care unit for more than 1 week. CIPNM may present with muscle weakness and
failure to wean from mechanical ventilation, but is discovered more often and
earlier by electrophysiological examination. In this review, the incidence,
clinical and electrophysiological features, differential diagnosis and prognosis
of CIPNM will be described. Risk factors for CIPNM are sepsis or systemic
inflammatory response syndrome and the severity of multi-organ failure. Presence
of CIPNM is associated with higher mortality rate, prolonged duration of
mechanical ventilation and prolonged rehabilitation. The majority of survivors
with CIPNM have persistent functional disabilities and a reduced quality of life.
There is need for new therapeutic strategies to prevent or minimize CIPNM in
critically ill patients.
PMID- 17038034
TI - Chronic polyneuropathy and Lyme disease.
AB - Infection of the peripheral nervous system with Borrelia burgdorferi can present
as a cranial neuropathy or radiculopathy with cerebrospinal fluid (CSF)
pleocytosis and intrathecal antibody production against B. burgdorferi, or as an
asymmetric peripheral neuropathy with acrodermatitis chronica atrophicans (ACA)
and normal CSF findings. According to North American studies, it can also present
as a symmetric chronic polyneuropathy without ACA or other Lyme manifestations.
Our purpose was to investigate the prevalence of B. burgdorferi antibodies in
patients presenting with isolated chronic polyneuropathy (PN) in a European
region with high incidence of Lyme disease. Sera from 209 PN patients and 247
healthy blood donors from Vest-Agder County, Norway, were examined. Borrelia
burgdorferi antibodies were detected in 43 (21%) PN patients and in 45 (18%)
healthy blood donors (P = 0.553). The prevalence of B. burgdorferi antibodies was
similar (P = 0.311) in cryptogenic PN (24/102, 24%) and PNs of identified
etiologies (19/107, 18%). PN patients with B. burgdorferi antibodies had normal
spinal fluid white cell count and they did not differ clinically or
electrophysiologically from PN patients without antibodies. None of 20 antibody
positive PN patients responded to antimicrobial treatment. The study shows that,
in Europe, chronic distal PN without ACA or other Lyme manifestations is very
rarely caused by a B. burgdorferi infection.
PMID- 17038035
TI - Apolipoprotein E epsilon4 allele is associated with the volume of white matter
changes in patients with lacunar infarcts.
AB - The relationship between the apolipoprotein E (APOE) exon 4 polymorphism and
white matter changes (WMC) in elderly subjects or patients with Alzheimer's
disease is controversial. To investigate this polymorphism in relation to WMC in
patients with lacunar infarcts, we prospectively observed 67 patients with acute
lacunar infarct and 134 age- and sex-matched controls. Genotypes were determined
using a nested polymerase chain reaction. WMC were measured quantitatively and
were divided into two groups, severe and mild, with the mean volume of WMC as the
cut point. Twenty-two patients (33%) had severe WMC. There was a significant
difference in the distribution of APOE epsilon2, epsilon3, and epsilon4 alleles
between severe and mild WMC groups (P = 0.002). The frequency of epsilon4 alleles
was higher in patients with severe WMC than in those with mild WMC (25% vs. 7%, P
= 0.003). These results suggest that APOE epsilon4 may exacerbate WMC in patients
with lacunar infarcts. Further studies are required to confirm this finding.
PMID- 17038036
TI - Isolated ocular motor nerve palsy in dural carotid-cavernous sinus fistula.
AB - The incidence of dural carotid-cavernous sinus fistula (DCCF) presenting as
isolated ocular motor nerve palsies without congestive ocular features is
unknown. We reviewed the DCCF patients in our hospital during the last 10 years
to elucidate the clinical and neuroradiological features of DCCF with isolated
ocular motor nerve palsy. Eleven amongst the 33 DCCF patients presented isolated
ocular motor nerve palsy. All the 11 patients underwent brain CT/CT angiography
(CTA) and/or MRI/MR angiography (MRA), before the digital subtraction angiography
(DSA). The compromised nerves were the oculomotor nerve in eight (72.7%),
abducens nerve in two (18.2%) and trochlear nerve in one (9.1%). Brain CT and/or
CTA were conducted in four patients but all unremarkable. MRI and/or MRA were
performed in nine patients and six of them showed compatible findings of DCCF.
The diagnoses of DCCFs were confirmed by DSA and all were posterior-draining
type. The outcome was good, with a total recovery rate of 54.5% within 12 months.
Thirty-three percent (11 of 33) of our DCCF patients presented with isolated
ocular motor nerve palsy, which is not uncommon. MRI and MRA are of value in the
initial evaluation, but DSA is necessary for the accurate diagnosis and treatment
planning.
PMID- 17038037
TI - Examination of the diagnostic validity of 'headache attributed to whiplash
injury': a controlled, prospective study.
AB - Acute and chronic headache attributed to whiplash injury are new diagnostic
entities in the International Classification of Headache Disorders, second
edition. A main objective of the present study was to assess the validity of
these nosologic entities by studying the headache pattern in an inception cohort
of 210 rear-end car collision victims and in 210 matched controls. Consecutive
drivers involved in rear-end collisions were identified from the daily records of
the Traffic Police Department of Kaunas, Lithuania. A standard self-report
questionnaire was sent to the drivers between 2 and 7 days after the collision,
and their passengers were recruited as well. Headache and neck pain were
evaluated within 7 days of the collision, at 2 months and 1 year after the
collision. A control group of non-traumatized subjects received questionnaires at
the time of the selection and 1 year later. Of the 75 collision victims who
developed headache within the first 7 days of the collision, 37 had a clinical
picture in accordance with the criteria for acute whiplash headache (i.e.,
concomitant neck pain) and 38 did not. For acute headache after collision,
concomitant neck pain was of no relevance to the headache type or its course. In
both these subgroups, migraine and tension-type headache could be diagnosed in
similar proportions and the prognosis after 2 months and 1 year was also similar.
Preexisting headache was a strong prognostic factor in both groups for both acute
and chronic pain. Compared with the non-traumatized control group, the 1-year
incidence of new or worsened headache, or of headache improvement, was the same.
A likely interpretation of the data is that acute headaches after rear-end car
collisions mainly represent episodes of a primary headache precipitated by the
stress of the situation. We conclude that the nosologic validity of both acute
and chronic whiplash headache is poor as the headaches, in accordance with the
criteria lack distinguishing clinical features and have the same prognosis
compared with headaches in a control group.
PMID- 17038038
TI - Headache prevalence related to smoking and alcohol use. The Head-HUNT Study.
AB - The aim of this study was to examine a possible association between smoking,
alcohol and headache in a large population-based cross-sectional study. A total
of 51,383 subjects completed a headache questionnaire and constituted the 'Head
HUNT' Study. Questionnaire-based information on smoking was available in 95% and
on alcohol in 89% of the individuals. Associations were assessed in multivariate
analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals
(CI). Prevalence rates for headache were higher amongst smokers compared with
never smokers, most evident for those under 40 years smoking more than 10
cigarettes per day (OR 1.5, 95% CI 1.3-1.6). Passive smoking was also associated
with higher headache prevalence. For alcohol use, there was a tendency of
decreasing prevalence of migraine with increasing amounts of alcohol consumption
compared with alcohol abstinence. Only with regard to symptoms indicating alcohol
overuse, a positive association with frequent headache was found. The association
between headache and smoking found in the present study raises questions about a
causal relationship, e.g. that smoking causes headache or that it allays stress
induced by headache. The observed negative association between migraine and
alcohol consumption is probably explained by the headache precipitating
properties of alcohol.
PMID- 17038039
TI - Validation of the deCODE Migraine Questionnaire (DMQ3) for use in genetic
studies.
AB - We assessed the reliability of the diagnosis of migraine with aura (MA) and
migraine without aura (MO) based on the third edition of the deCODE Migraine
Questionnaire (DMQ3) using a physician-conducted interview as an empirical index
of validity. Amongst Danish migraine families recruited from specialist practice
we selected 200 cases diagnosed according to the International Classification of
Headache Disorders 2nd Edition in a validated physician-conducted telephone
interview: 50 patients with exclusively MA, 50 with both MA and MO, 50 with
exclusively MO and 50 controls. A written copy of the DMQ3 was mailed to the
participant. The DMQ3-based diagnosis was compared with the interview-based
diagnosis. Overall, the DMQ3 diagnosed migraine (MA, MO or both) with a
sensitivity of 99% (109/110), a specificity of 86% (32/37) and a kappa statistic
of 0.89. The most reliable subtype of migraine was MA (with or without co
occurring attacks of MO) which was diagnosed with a sensitivity of 92% (71/77), a
specificity of 93% (65/70) and a kappa statistic of 0.85. Exclusively MO was
diagnosed with a sensitivity of 91% (30/33), a specificity of 93% (106/114) and a
kappa statistic of 0.80. Weakest was the diagnosis of both MO and MA which was
diagnosed with a sensitivity of 63% (24/38), a specificity of 92% (100/109) and a
kappa statistic of 0.57. In conclusion, the DMQ3 is a valid tool for diagnosing
patients with migraine for genetic studies.
PMID- 17038040
TI - Acute autonomic dysfunction contralateral to acute strokes: a prospective study
of 100 consecutive cases.
AB - Complex painful reflex syndrome is sometimes described in the chronic phase of
stroke. Acute autonomic dysfunction (AAD), which is occasionally present in cases
of acute stroke, has not been studied prospectively. The aim of the study was to
investigate AAD on the hemibody contralateral to the lesion in the acute phase of
stroke. One hundred consecutive patients (median age +/- interquartile range, 74
+/- 21; range 19-93; 51 women: 80 +/- 17 and 49 men: 70 +/- 17 years) in the
acute phase of stroke were studied prospectively. Changes in skin temperature or
coloration, diaphoresis, pain, or edema were noted in the first 3 days post
stroke. Associations between AAD and topography (cortical pre- and/or post
central, insular, corona radiata, basal ganglia, internal capsule, thalamus, and
brainstem), age, gender, ischemic or hemorrhagic etiology, or the presence of
sensorimotor deficits or ataxia were examined using the chi-squared or Fisher's
exact test and logistic regression analysis. AAD was found in 71% of the patients
and showed a significant positive association with the presence of a lesion in
the post-central cortex (P = 0.037), internal capsule (P = 0.005), basal ganglia
(P = 0.002), or insula (P = 0.011) and a negative association with the presence
of a lesion in the brainstem (P = 0.004). Multivariate logistic regression
analysis including all studied topographic variables showed that only brainstem
lesions were significantly associated with a decreased risk of developing AAD
(odds ratio = 0.08, 95% confidence interval: 0.01-0.69, P = 0.022). AAD was not
associated with age, gender, the ischemic or hemorrhagic nature of the lesion,
the side of lesion, hypertonic or hypotonic paresis, or hyperreflexia or
hyporeflexia. AAD was found in association with sensory deficits (P = 0.001) and
contralateral hyperkinesia (P = 0.004). Acute AAD is significantly more likely to
occur in the presence of hemispheric lesions involving sensory pathways from the
cortex to the internal capsule and insula and is significantly less prevalent in
the presence of brainstem lesions.
PMID- 17038041
TI - Factors influencing hemorrhagic transformation in ischemic stroke: a
clinicopathological comparison.
AB - As hemorrhagic transformation (HTr) is a frequent complication and can worsen the
outcome of acute ischemic stroke, our aim was to assess the risk factors of HTr.
Using the database of our neuropathological laboratory, 245 consecutive acute
ischemic stroke patients were analyzed. An exploratory logistic regression
procedure was carried out to find the best multiple model identifying the factors
associated with HTr. The autopsy revealed ischemic infarct in 175 (71%) and
ischemic infarct with HTr in 70 (29%) patients. Mean age was 71.5 +/- 11.4 years
(mean +/- SD) and 74.8 +/- 10.2 years (mean +/- SD), respectively. The multiple
model confirmed age in case of embolic stroke, and diabetes mellitus and infarct
size as independent risk factors of HTr. It seems that not serum glucose level
but diabetes mellitus in the case history is an independent predictor of HTr.
PMID- 17038042
TI - Stroke complicating pregnancy and the puerperium.
AB - Stroke complicating pregnancy and the puerperium in Taiwan and the comparison
between Western and Eastern countries have not been well studied. We identified
retrospectively 32 cases of stroke from 66,781 deliveries, including 21
intracranial hemorrhages and 11 cerebral infarctions from 1992 to 2004. The most
common causes of intracranial hemorrhage were vascular anomaly (29%), pre
eclampsia/eclampsia (24%), undetermined (24%) and coagulopathy (19%). The most
common causes of cerebral infarction were cardioembolism (36%), cerebral venous
thrombosis (27%) and pre-eclampsia/eclampsia (18%). Perinatal adverse outcome
included two stillbirths, nine premature deliveries and four abortions. The
compiled results of previous studies and ours revealed that intracranial
hemorrhage appeared to be slightly more common in Taiwan (43-69%) than in the
Western countries (33-52%). The average maternal mortality rate was 17.8% (range
9-38) with 77.8% due to intracranial hemorrhage. The average incidence of stroke
associated with pregnancy and the puerperium was 21.3 per 100,000 deliveries
(range 8.9-67.1). Our study, different from the Western countries, showed that
intracranial hemorrhage is slightly more common than cerebral infarction. Pre
eclampsia/eclampsia is an important cause of stroke, however, the possibility of
cardioembolism in cerebral infarction and vascular anomaly in intracranial
hemorrhage should be studied.
PMID- 17038043
TI - Asymptomatic pontine myelinolysis.
AB - A 43-year-old lady presented with bilateral foot drop due to alcohol-related
peripheral neuropathy. There was no history of electrolyte disturbance or altered
consciousness. Cranial nerve, bulbar and pyramidal symptoms and signs were
absent. Nerve conduction studies confirmed the neuropathy. Inadvertently
requested neuroimaging of brain demonstrated signal change typical of central
pontine myelinolysis. Asymptomatic pontine myelinolysis occurs rarely in
alcoholics in the absence of bulbar dysfunction. It is important for physicians
to be aware of the clinical entity of asymptomatic pontine myelinolysis to avoid
misinterpretation of abnormalities detected on cerebral imaging in alcoholic
individuals.
PMID- 17038044
TI - Isolated sixth nerve palsy secondary to spontaneous intracranial hypotension.
AB - We report the case of a 43-year-old gentleman who presented with an isolated left
sixth nerve palsy in association with postural headache. Magnetic resonance
imaging showed dural enhancement with downward displacement of the brainstem.
This, in association with the signs, symptoms and findings on lumbar puncture,
confirmed the diagnosis of spontaneous intracranial hypotension. Treatment was
successful with epidural blood patching. The case is discussed and the relevant
literature reviewed.
PMID- 17038045
TI - Knowledge about the genetics of essential tremor in patients and their relatives.
AB - In a face-to-face questionnaire-based survey involving a total of 111 essential
tremor (ET) patients and their relatives, we demonstrated a general lack of
genetic insight amongst our study subjects. There was no significant correlation
between genetic knowledge of ET and age, level of education, disease duration or
severity. A proactive effort is needed to encourage physicians managing ET
patients to incorporate genetic information and education into their practice.
PMID- 17038047
TI - Novel overlapping coding sequences in Chlamydia trachomatis.
AB - Chlamydia trachomatis is the aetiological agent of trachoma and sexually
transmitted infections. The C. trachomatis genome sequence revealed an organism
adapted to the intracellular habitat with a high coding ratio and a small genome
consisting of 1.042-kilobase (kb) with 895 annotated protein coding genes. Here,
we repredict the protein-coding genes of the C. trachomatis genome using the gene
finder EasyGene that was trained specifically for C. trachomatis, and compare it
with the primary C. trachomatis annotation. Our work predicts 15 genes not listed
in the primary annotation and 853 that are in agreement with the primary
annotation. Forty two genes from the primary annotation are not predicted by
EasyGene. The majority of these genes are listed as hypothetical in the primary
annotation. The 15 novel predicted genes all overlap with genes on the
complementary strand. We find homologues of several of the novel genes in C.
trachomatis Serovar A and Chlamydia muridarum. Several of the genes have typical
gene-like and protein-like features. Furthermore, we confirm transcriptional
activity from 10 of the putative genes. The combined evidence suggests that at
least seven of the 15 are protein coding genes. The data suggest the presence of
overlapping active genes in C. trachomatis.
PMID- 17038048
TI - Binding of Streptococcus gordonii to extracellular matrix proteins.
AB - Knock-out mutants of Streptococcus gordonii Challis were constructed and assayed
for binding to extracellular matrix proteins (EMPs) by enzyme-linked
immunosorbent assay (ELISA). It was shown that (i) the mutant lacking the cell
wall polysaccharide receptor could no longer bind type I and type II collagen,
(ii) the mutant lacking the fibronectin-binding proteins CshA and FbpA was also
strongly impaired in collagen binding and (iii) the mutant lacking the methionine
sulfoxide reductase MsrA was significantly impaired in fibronectin binding. Our
results indicate that binding to EMPs by S. gordonii is a multifactorial process
controlled by genes located at three different chromosomal sites.
PMID- 17038049
TI - Application of signature-tagged mutagenesis to the study of virulence of Erwinia
amylovora.
AB - To identify genes that contribute to the virulence of Erwinia amylovora in
plants, 1892 mutants were created and screened in pools of < or =96 mutants using
signature-tagged mutagenesis. Nineteen mutants were not recovered from apple
shoots following inoculation, which suggested that the insertions in these
mutants affected genes important for bacterial survival in planta. DNA flanking
the Tn5 insertions in the 19 mutants was sequenced and analysed by blast. One
mutant had a Tn5 insertion in amsE, a gene involved in the biosynthesis of
exopolysaccaride (EPS). Fourteen mutants had insertions in loci that were
implicated in biosynthesis or transport of particular amino acids or nucleotides,
a site-specific recombinase active during cell division and several putative
proteins of unknown function; the flanking DNA of the remaining four mutants
lacked significant homology with any DNA in the database. When inoculated
individually to hosts, 10 of the 19 mutants caused significantly less disease and
multiplied less, as compared with the wild-type strain.
PMID- 17038050
TI - Role of 1-hydroxybenzotriazole in oxidation by laccase from Trametes versicolor.
Kinetic analysis of the laccase-1-hydroxybenzotriazole couple.
AB - In the current studies, we used Lineweaver-Burke analysis to examine the role of
1-hydroxybenzotriazole (HBT) in the oxidation of various compounds by laccase
from Trametes versicolor. At low concentrations, HBT was a competitive inhibitor
of the oxidation, but at high concentrations, it was a noncompetitive inhibitor.
Analysis of the oxidation of ferrocytochrome c by the laccase-HBT couple showed
that increasing the concentration of ferrocytochrome c did not affect the V(max)
but reduced the apparent K(m). In addition, in the manganese peroxidase-Mn(II)
reaction, which is a typical oxidation system by mediator, the apparent K(m) and
V(max) increased as the concentration of the substrate 2,6-dimethoxyphenol was
increased. These results indicate that HBT is involved in the binding of laccase
and substrates that laccase cannot oxidize alone.
PMID- 17038051
TI - Silencing of natural interferon producing cell activation by porcine circovirus
type 2 DNA.
AB - Porcine circovirus type 2 (PCV2) infection of natural interferon producing cells
(NIPCs) impairs the induction of interferon (IFN)-alpha and tumour necrosis
factor (TNF)-alpha by cytosine-phosphorothioate-guanine (CpG)
oligodeoxynucleotides (ODNs), thereby preventing both their autocrine maturation
and the paracrine maturation of myeloid dendritic cells (DCs). The present study
shows that the PCV2-mediated inhibition of NIPCs was mediated by viral DNA,
although it was independent of virus replication. The inhibitory effect of PCV2
DNA was more diversified than if it had simply targeted CpG-ODN-induced cytokines
(IFN-alpha, TNF-alpha, interleukin-6, IL-12). A broad spectrum inhibition was
noted, affecting responses induced by toll-like receptor (TLR)-7 and TLR9
agonists, as well as viruses including pseudorabies virus, transmissible
gastroenteritis virus and classical swine fever virus. From these results, it
would appear that PCV2 DNA can induce a dominant negative signal influencing
independent pattern recognition receptor-induced activation cascades. Despite a
concomitant internalization of PCV2 DNA and CpG-ODNs, no colocalization was
observed, indicating that PCV2 DNA and CPG-ODNs may not target the same receptor.
This study describes a novel modulation of the innate immune response, which
would render the host more susceptible to secondary or concomitant microbial
infections.
PMID- 17038053
TI - Oral hygiene practices, periodontal conditions, dentition status and self
reported bad mouth breath among young mothers, Tanzania.
AB - OBJECTIVES: To determine the oral hygiene practices, periodontal conditions,
dentition status and self-reported bad mouth breath (S-BMB) among young mothers.
STUDY PARTICIPANTS AND METHODS: This was a cross-sectional descriptive study
conducted at Muhimbili National Hospital, Dar es Salaam, Tanzania. A total of 302
postpartum mothers, aged 14-44 years, were interviewed on oral hygiene practices
and S-BMB using structured questionnaire. Oral hygiene, dentition and periodontal
status were assessed using the Community Periodontal Index probe and gingival
recessions (GR) using Williams Periodontal probe. RESULTS: Tooth brushing
practice was 99%; tongue brushing (95%), plastic toothbrush users (96%), chewing
stick (1%), wooden toothpicks (76%), dental floss (<1%); and toothpaste (93%).
The prevalence of plaque and gingival bleeding on probing was 100%, gum bleeding
during tooth brushing (33%), calculus (99%), probing periodontal pocket depth
(PPD) 4-5 mm (27%), PPD 6+ mm (3%), GR 1+ mm (27%) and tooth decay (55%). The
prevalence of S-BMB was 14%; the S-BMB had higher mean number of sites with
plaque compared to the no S-BMB group (P=0.04). Factors associated with S-BMB
were gum bleeding on tooth brushing (OR=2.4) and PPD 6+ mm (OR=5.4). CONCLUSION:
Self-reported bad mouth breath is a cause of concern among young mothers, and
associated significant factors were gum bleeding on tooth brushing and deep
periodontal pockets of 6+ mm. Further research involving clinical diagnosis of
bad mouth breath and intervention through oral health promotion and periodontal
therapy are recommended. CLINICAL RELEVANCE: This study provides baseline
information on oral health status and the complaint on bad mouth breath which
necessitates in the future need for objective assessment, diagnosis and
management of bad mouth breath for enhanced social and professional interaction
without embarrassment.
PMID- 17038054
TI - Oral health knowledge and practices among Dar es Salaam institutionalized former
street children aged 7-16 years.
AB - OBJECTIVES: To find out level of knowledge on causes and prevention of dental
caries and bleeding gums, oral hygiene and eating practices among
institutionalized former street children. METHODS: A structured standardized
questionnaire was used to collect data for this study. Chi-square test was used
to test for significant differences. RESULTS AND CONCLUSIONS: Eighty-eight per
cent and 83% of the children knew the cause of tooth decay and bleeding gums
respectively and 17-68% were aware of preventive measures. At the institutions
visited, 92% of the children said they brush their teeth but 74% brushed when
living on the streets, this difference was significant (chi2=4.40, P=0.05). About
half did not use toothpaste during street life, whilst 8% do not use toothpaste
at institutions, the difference was significant (chi2=5.081, P=0.025). Almost 22%
use sweets and biscuits at institutions, about 44% used the snacks when living on
the streets, the differences were significant (chi2=3.798, P=0.04, and
chi2=3.893, P=0.04). Only 6% use sodas and sweetened juices at institutions,
while 32-36% used the drinks during street life, the differences were significant
(chi2=4.38 P=0.05 and chi(2)-12.87, P=0.01). The findings of this study show that
most former street children are aware of the causes of dental caries and bleeding
gums but have poor knowledge on prevention of the two diseases. Furthermore,
children living on the streets are more likely to eat cariogenic foods and have
poor oral hygiene practices.
PMID- 17038055
TI - Screening for type 2 diabetes mellitus using gingival crevicular blood.
AB - This study was conducted to assess the usefulness of the gingival crevicular
blood for estimating the glucose level during routine periodontal examination
using Xitux Diagnostics Smart-X self-monitoring blood glucose device among
Jordanian patients attending dental teaching clinics. A total of 34 type 2
diabetic patients (18 males and 16 females) and 26 non-diabetic patients (14
males and 12 females) participated in this study. Glucose level was measured in a
sample of gingival crevicular blood and in another sample obtained by finger
puncture using a self-monitoring device. Glucose measurements from gingival
crevicular blood samples, ranged from 57 to 250 mg dl-1 with a mean of 125.4+/
60.7 mg dl-1 (+/-SD) and glucose measurements obtained by finger puncture, ranged
from 62 to 263 mg dl-1 with a mean of 131.9+/-61.1 mg dl-1. Pearson's correlation
coefficient was performed to assess the correlation between the glucose
measurements in these two samples. Pearson's correlation coefficient showed an
almost perfect positive correlation between the gingival readings and finger
puncture readings (r=0.997, P<0.0001). In conclusion, gingival crevicular blood
can provide an acceptable source for measuring blood glucose level. However, the
technique to obtain an acceptable blood sample from gingival crevices is not
always feasible which would limit its application as a clinical practice.
Additional studies that refine this technique and use larger sample size are
recommended.
PMID- 17038057
TI - Siwak as a oral hygiene aid in patients with fixed orthodontic appliances.
AB - OBJECTIVES: The aims of this study were to compare the mechanical efficacy of
Siwak in plaque control and gingival health conditions in subjects wearing fixed
orthodontic appliances compared with standard and orthodontic toothbrushes.
METHODS: Forty male patients with a mean age of 17.20+/-4.01 years, wearing fixed
orthodontic appliances were included in this study. Following a session of
scaling and polishing, which established a situation with minimal gingival
inflammation and close to zero amounts of dental plaque, all patients were
instructed to use a standard soft toothbrush for 1 week after which they were
randomly and equally allocated to one of four groups: (i) a manual toothbrush
group; (ii) an orthodontic toothbrush group; (iii) a Siwak group; and (iv) a
combination of Siwak and an orthodontic toothbrush group. All patients were
instructed to brush their teeth three times a day. All patients were scored for
plaque and gingivitis 1 week after scaling and polishing and 2 weeks following
group assignment. RESULTS: A similar effect of Siwak to that of soft and
orthodontic toothbrushes with respect to plaque control in patients with fixed
orthodontic appliances was found. It was the combined use of Siwak and
orthodontic toothbrush that provided the best plaque control in such patients.
Gingival condition was better in the Siwak groups whether used solely or in
combination with an orthodontic toothbrush. CONCLUSION: The use of Siwak promotes
gingival health in patients with orthodontic appliances.
PMID- 17038056
TI - A comparison of two chlorhexidine gel brushing regimens and a conventional
toothpaste brushing regimen for the development of tooth staining over a 6-week
period.
AB - AIMS: A single-centre, randomized single-blind parallel study was undertaken to
compare staining seen with three brushing regimens and to determine subject
perception of side effects such as staining and effects on taste. METHODS: This 6
week parallel study used 157 volunteers who were randomized into one of three
treatment groups: (i) brushing in the morning and evening with a normal dose of a
1% chlorhexidine gel, (ii) brushing with a low dose of chlorhexidine gel in the
evening and a whitening dentifrice in the morning, and (iii) brushing with a
standard fluoride paste in the morning and evening. Following home usage of their
allocated products, the study volunteers returned after 3 and 6 weeks to record
the amount of stain present. After the 6-week period, subject perception of taste
and stain acceptability was determined using a questionnaire. RESULTS: After 6
weeks of use of the low-dose chlorhexidine gel and whitening dentifrice,
significantly more stain was seen compared with the use of a standard dentifrice
(P<0.0001). Similarly, significantly more stain was seen with use of the normal
dose chlorhexidine gel compared with the low-dose gel and whitening dentifrice
(P=0.0007). Approximately 30% of individuals on the low-dose chlorhexidine gel
regimen found the amount of stain unacceptable and 10% noted an effect on their
taste perception. CONCLUSIONS: The use of low dose of chlorhexidine gel at night
and a whitening paste in the morning produced a significant amount of stain that
30% of subjects considered unacceptable.
PMID- 17038058
TI - Oral health in Florida nursing homes.
AB - OBJECTIVES: The purpose of this study was to measure the oral health and hygiene
status among 265 South Florida nursing home residents aged between 45 and 98
years. METHODS: The oral health and hygiene status of the residents were assessed
by noting the presence of calculus, caries, gingivitis, cheilitis, apthous ulcer,
dry mouth and red or white lesions. RESULTS: The incidence of nursing home
residents with calculus was 79.6% and the remaining 20.4% were edentulous. More
than half of residents had oral problems (50.6%) the commonest was gingivitis
(36.6%), followed by caries (26%) and tooth fracture (15.9%). Almost half the
residents wore dentures (47.2%). Statistical analysis was conducted using
analysis of variance (P-values). Ageing of the residents was statistically
correlated to a worsening of oral hygiene status (P<0.0066), absence and presence
of one or two dentures (P<0.0034) and a loss of teeth (P<0.0001). CONCLUSIONS:
The ageing of residents is correlated to increasing oral health problems and the
loss of teeth. Oral health neglect affects almost all of the nursing home
residents. Care providers should receive education and training from dental
hygienists to improve the standard of oral hygiene and health of the elderly.
PMID- 17038059
TI - Evaluation of several brushing motion combinations in relation to plaque-removing
efficacy with Oral-B CrossAction Power: a professional brushing study.
AB - AIM: The aim of this study was to evaluate the additional effect of a newly
developed battery-operated brush Oral-B CrossAction Power with a hybrid brush
head design (CAPB). The brush combines an oscillating/rotating part, a
PowerHead(R), with a non-moving part with CrissCross bristles. It was compared
with a manual control toothbrush Butler GUM 311 (CTB). MATERIAL AND METHODS:
Thirty subjects were requested not to brush their teeth 48 h prior to the
examination, when plaque removal efficacy was assessed by scoring plaque before
and after brushing. Plaque was assessed according to the Silness & Loe Index at
six sites per tooth. Subjects were brushed by a dentist using one of the four
randomly chosen procedures of brushing in each quadrant. The CAPB was used with
three different modes of brushing each in different randomly chosen quadrants,
with the manual toothbrush being used in the remaining quadrant as a control.
RESULTS: The baseline plaque levels ranged from 1.69 to 1.74 and the end levels
ranged from 0.39 to 0.45. In terms of percentage, the results with the four
procedures run from 75% to 79%. These differences between the battery brush and
manual brush irrespective of the brushing mode used were not statistically
significant. CONCLUSION: The results of this Professional Brushing Study show
that the CrossAction Power toothbrush was as effective as a regular manual
toothbrush.
PMID- 17038060
TI - Severe enamel abrasion due to misuse of an air polishing device.
AB - OBJECTIVES: In this case report, a 28-year-old male patient who severely injured
the enamel tissue of his upper incisors due to excessive self-performed air
polishing has been presented. Air polishing devices are frequently used in
initial or supportive periodontal therapy to remove supragingival plaque and
dental stains. Enamel tissue is minimally affected by air polishing when
appropriately performed by a professional. However, excessive air polishing may
have detrimental effects even on the intact enamel. The aim of this case report
is to present a patient who severely injured the enamel surfaces of his upper
incisors due to excessive self-performed air polishing. METHODS: A case of severe
enamel abrasions in a 28-year-old male patient who injured the enamel surfaces of
his upper incisors following several self-performed air polishing sessions has
been presented. RESULTS: Severely abraded enamel surfaces of the upper incisors
were present and during the course of therapy restored by composite restorations
to establish a satisfactory clinical appearance. CONCLUSIONS: In clinical
practice, air polishing can be performed rather safely on intact enamel and is a
beneficial procedure in initial and supportive periodontal therapy when performed
by a professional under recommended operating conditions. However, review of the
literature reveals that air polishing may be harmful on tooth and surrounding
structures unless carried out cautiously. Furthermore, excessive use of air
polishing devices, especially by unauthorized personnel may be damaging and lead
to severe abrasion of enamel tissue.
PMID- 17038065
TI - Dissemination of the hospital elder life program: implementation, adaptation, and
successes.
AB - OBJECTIVES: To describe the Hospital Elder Life Program (HELP) across
dissemination sites, to detail adaptations, and to summarize advantages across
sites. DESIGN: Cross-sectional survey. SETTING: HELP sites in acute care
hospitals. PARTICIPANTS: Thirteen sites that enrolled 11,344 patients.
MEASUREMENTS: Seventy-five closed- and open-ended questions describing details of
the HELP site, procedures, staffing, outcomes tracked, and advantages. RESULTS:
As of July 1, 2005, HELP had been fully implemented in 13 sites, with a median
duration of 24 months (range 6.0-38.0). Although a high degree of fidelity to the
original model was maintained, variations existed in staffing patterns, outcome
tracking, and recommended HELP procedures. Adaptations were made across multiple
domains, including enrollment criteria at 15.4% of sites, screening and
assessment tools at 61.5%, and individual intervention protocols at 15.4% to
30.8%. Local circumstances drove these adaptations, with the most common reasons
being lack of adequate staffing and logistical constraints. All sites conducted
regular HELP staff meetings; other recommended quality assurance procedures were
conducted at 46.2% to 92.3% of sites. Reported advantages of HELP included
providing an educational resource at 100% of sites, improving hospital outcomes
(e.g., delirium and functional decline) at 100%, providing nursing education and
improving retention at 100%, enhancing patient and family satisfaction with care
at 92.3%, raising visibility for geriatrics at 92.3%, and improving quality of
care at 84.6%. CONCLUSION: This report describes the real-world implementation of
HELP across 13 sites, documents their local adaptations and successes, and
provides insight into how motivated institutions can create change to improve
quality of care for older persons.
PMID- 17038066
TI - Community-acquired bacterial meningitis in older people.
AB - OBJECTIVES: To describe clinical features of bacterial meningitis in older
people. DESIGN: Cohort study. SETTING: Hospitals in the Netherlands.
PARTICIPANTS: Patients aged over 16 with community-acquired bacterial meningitis,
confirmed using cerebrospinal fluid culture. MEASUREMENTS: Data were collected
prospectively. The cohort was dichotomized with respect to age (>or=60 vs 17-59).
RESULTS: Two hundred fifty-seven of 696 episodes of community-acquired bacterial
meningitis (37%) occurred in elderly patients and 439 (63%) in younger adults.
Older people more often presented with the triad of fever, neck stiffness, and
altered mental status than younger adults (58% vs 36%; P<.001). In older people,
meningitis was due to Streptococcus pneumoniae in 176 episodes (68%). In younger
adults, Neisseria meningitidis was the most common pathogen, responsible for 221
episodes (50%). Elderly patients more often developed complications than younger
adults (72% vs 57%; P<.001), which resulted in a higher mortality rate (34% vs
13%; P<.001). Older people tended to die more often from cardiorespiratory
failure (25% vs 11%; P=.06), whereas younger adults more often died from brain
herniation (23% vs 2%; P=.004). CONCLUSION: Elderly patients with bacterial
meningitis often present with classic symptoms of bacterial meningitis. Bacterial
meningitis within this age group is predominantly due to S. pneumoniae and is
associated with high morbidity and mortality rates. Whereas older people die
frequently of cardiorespiratory failure, younger adults more often die of brain
herniation.
PMID- 17038067
TI - Use of selective serotonin reuptake inhibitors and sleep disturbances in
community-dwelling older women.
AB - OBJECTIVES: To determine the association between use of selective serotonin
reuptake inhibitors (SSRIs) and objective measures of sleep disturbances in older
community-dwelling women, including women without evidence of depression. DESIGN:
Cross-sectional study. SETTING: Four U.S. clinical centers. PARTICIPANTS: Two
thousand eight hundred fifty-three women aged 71 and older (2,630 nonusers of
antidepressants and 223 taking SSRIs alone, not in combination with other
antidepressants). MEASUREMENTS: Medication use, assessed using an interviewer
administered questionnaire with verification of use from medication containers
and computerized dictionary used to categorize type of medication; evidence of
depression assessed using self-report or a score of 6 or higher on the Geriatric
Depression Scale; and sleep parameters measured using a wrist actigraph, with
data collected for an average of four consecutive 24-hour periods. RESULTS: Of
the overall cohort of 2,853 women and of 2,337 women without evidence of
depression, sleep disturbances were more common in women taking SSRIs than in
those not taking antidepressants. After excluding women with evidence of
depression and adjusting for multiple potential confounders, women taking SSRIs
were more likely to have a sleep duration of 5 hours or less (multivariate odds
ratio (MOR)=2.15, 95% confidence interval (CI)=1.04-4.47), sleep efficiency less
than 70% (MOR=2.37, 95% CI=1.32-4.25), sleep latency of 1 hour or more (MOR=3.99,
95% CI=2.29-6.96) and eight or more long wake episodes (MOR=1.75, 95% CI=0.99
3.10). CONCLUSION: SSRI use by older women, including those without evidence of
depression, is associated with a greater likelihood of sleep disturbances,
including poorer sleep efficiency, longer sleep latency, and sleep fragmentation,
manifested by multiple long wake episodes. These results add to the uncertainty
regarding risks and benefits of SSRI use in aged populations.
PMID- 17038068
TI - Polypharmacy and prescribing quality in older people.
AB - OBJECTIVES: To evaluate the relationship between inappropriate prescribing,
medication underuse, and the total number of medications used by patients.
DESIGN: Cross-sectional study. SETTING: Veterans Affairs Medical Center.
PARTICIPANTS: One hundred ninety-six outpatients aged 65 and older who were
taking five or more medications. MEASUREMENTS: Inappropriate prescribing was
assessed using a combination of the Beers drugs-to-avoid criteria (2003 update)
and subscales of the Medication Appropriateness Index that assess whether a drug
is ineffective, not indicated, or unnecessary duplication of therapy. Underuse
was assessed using the Assessment of Underutilization of Medications instrument.
All vitamins and minerals, topical and herbal medications, and medications taken
as needed were excluded from the analyses. RESULTS: Mean age was 74.6, and
patients used a mean+/-standard deviation of 8.1+/-2.5 medications (range 5-17).
Use of one or more inappropriate medications was documented in 128 patients
(65%), including 73 (37%) taking a medication in violation of the Beers drugs-to
avoid criteria and 112 (57%) taking a medication that was ineffective, not
indicated, or duplicative. Medication underuse was observed in 125 patients
(64%). Together, inappropriate use and underuse were simultaneously present in 82
patients (42%), whereas 25 (13%) had neither inappropriate use nor underuse. When
assessed by the total number of medications taken, the frequency of inappropriate
medication use rose sharply from a mean of 0.4 inappropriate medications in
patients taking five to six drugs, to 1.1 inappropriate medications in patients
taking seven to nine drugs, to 1.9 inappropriate medications in patients taking
10 or more drugs (P<.001). In contrast, the frequency of underuse averaged 1.0
underused medications per patient and did not vary with the total number of
medications taken (P=.26). Overall, patients using fewer than eight medications
were more likely to be missing a potentially beneficial drug than to be taking a
medication considered inappropriate. CONCLUSION: Inappropriate medication use and
underuse were common in older people taking five or more medications, with both
simultaneously present in more than 40% of patients. Inappropriate medication use
is most frequent in patients taking many medications, but underuse is also common
and merits attention regardless of the total number of medications taken.
PMID- 17038069
TI - The epidemiology of bathing disability in older persons.
AB - OBJECTIVES: To quantify the burden of bathing disability over time; to determine
whether the burden of bathing disability differs according to age, sex, and
physical frailty; and to evaluate the relationship between disability in bathing
and disability in other essential activities of daily living (ADLs). DESIGN:
Prospective cohort study. SETTING: General community in greater New Haven,
Connecticut. PARTICIPANTS: Seven hundred fifty-four community-living older
persons aged 70 and older who were nondisabled (required no personal assistance)
in four essential ADLs: bathing, dressing, transferring from a chair, and walking
inside the house. MEASUREMENTS: Bathing disability, defined as the inability to
wash and dry one's whole body without personal assistance, was assessed every
month for up to 6 years, along with disability in dressing, transferring, and
walking. RESULTS: Over the course of 6 years, 440 participants (58.4%) had at
least one episode of bathing disability, and 266 (34.0%) had multiple episodes,
with the duration of each episode averaging about 6 months. Whether assessed as
number of episodes, duration of episodes, incidence rates, or number of months
per 100 months, the burden of bathing disability was greatest in participants who
were physically frail and was consistently higher in women than men and in
participants who were aged 80 and older than those who were aged 70 to 79. Most
episodes of bathing disability (86.1%) were not preceded in the prior month by
disability in dressing, transferring, or walking, and nearly half (48.3%) were
not accompanied at onset by disability in one or more of these other ADLs. In a
multivariable model that included age, sex, and physical frailty, the onset of
bathing disability increased the likelihood of developing disability in the other
essential ADLs the following month fivefold (hazard ratio=5.1, 95% confidence
interval=4.1-6.4). CONCLUSION: Disability in bathing may serve as a sentinel
event in the disabling process. Given the recurrent nature of bathing disability,
programs designed to enhance independent bathing will need to focus not only on
the prevention of bathing disability, but also on the restoration and maintenance
of independent bathing in older persons who become disabled.
PMID- 17038070
TI - Diagnosis and characteristics of syncope in older patients referred to geriatric
departments.
AB - OBJECTIVES: To test the applicability and safety of a standardized diagnostic
algorithm in geriatric departments and to define the prevalence of different
causes of syncope in older patients. DESIGN: Multicenter cross-sectional
observational study. SETTING: In-hospital geriatric acute care departments and
outpatient clinics. PARTICIPANTS: Two hundred forty-two patients (aged>or=65,
mean+/-standard deviation=79+/-7, range 65-98) consecutively referred for
evaluation of transient loss of consciousness to any of six clinical centers
participating in the study. Of these, 11 had a syncope-like condition (5
transient ischemic attack; 6 seizures), and 231 had syncope (aged 65-74, n=71;
aged>or=75, n=160). MEASUREMENTS: Protocol designed to define etiology and
clinical characteristics of syncope derived from European Society of Cardiology
Guidelines on syncope. RESULTS: No major complication occurred with use of the
protocol. Neurally mediated was the more prevalent form of syncope in this
population (66.6%). Cardiac causes accounted for 14.7% of all cases. The
neuroreflex form of syncope (vasovagal, situational, and carotid sinus syndrome)
was more common in younger than in older patients (62.3% vs 36.2%; P=.001),
whereas orthostatic syncope was more frequent in the older than in the younger
group (30.5% vs 4.2%; P<.001). In only 10.4% of cases, syncope remained of
unexplained origin. After initial evaluation, a definite diagnosis was possible
in 40.1% of the cases, and a suspected diagnosis was obtained in 57.9%. Syncope
of suspected cardiac origin after initial evaluation was confirmed in 43.7% of
cases, and neuromediated causes were confirmed in 83.5% of the cases. CONCLUSION:
The protocol is applicable even beyond the age of 90 in geriatric departments.
The standardized protocol is associated with a reduction in the frequency of
unexplained syncope to about 10%.
PMID- 17038071
TI - Clinical features of reflux esophagitis in older people: a study of 840
consecutive patients.
AB - OBJECTIVES: To compare symptoms and other clinical characteristics of reflux
esophagitis in patients of different ages. DESIGN: Observational cross-sectional
study of consecutive patients. SETTING: Geriatric Unit, Casa Sollievo della
Sofferenza Hospital, Istituto di Ricovero e Cura a Carattere Scientifico.
PARTICIPANTS: Eight hundred forty patients with endoscopically diagnosed erosive
esophagitis divided into four groups according to age (young (<50, mean 36.7,
n=114), adult (50-69, mean 59.1, n=126), elderly (70-84, mean 77.3, n=425), and
very elderly (>or=85, mean 88.4, n=175)). MEASUREMENTS: Gastrointestinal symptoms
were evaluated using the Gastrointestinal Symptom Rating Scale questionnaire.
Other symptoms were recorded when present as an indication for endoscopy.
Severity of esophagitis, presence of Helicobacter pylori infection, presence and
size of hiatus hernia, Barrett's esophagus, antrum or corpus gastric atrophy, and
nonsteroidal antiinflammatory drug (NSAID) use were also evaluated. RESULTS:
Elderly and very elderly patients had a significantly lower prevalence of typical
gastroesophageal reflux disease symptoms (heartburn or acid regurgitation
(P<.001) and epigastric pain (P<.001)) than young and adult patients. Conversely,
the prevalence of other symptoms (anorexia (P<.001), weight loss (P<.007), anemia
(P<.001), vomiting (P<.001), and dysphagia (P<.001)) significantly increased with
age. The prevalence of severe esophagitis (P<.001), hiatus hernia (P<.005), the
size of hiatus hernia (P<.001), antrum and corpus gastric atrophy (P<.05) and
NSAID use (P<.005) also significantly increased with age. Multivariate analysis
demonstrated that older age (65-84, odds ratio (OR)=2.66, 95% confidence interval
(CI)=1.38-5.12; >or=85, OR=4.57, 95% CI=2.15-9.71), hiatus hernia larger than 3
cm in diameter (OR=2.38, 95% CI=1.41-4.01), and male sex (OR=2.83, 95% CI=1.72
4.64) are independent risk factors for severe esophagitis, whereas H. pylori
infection, gastric atrophy, NSAID use, and the presence of hiatus hernia were
not. CONCLUSION: Elderly patients with reflux esophagitis had less-typical and
more-nonspecific symptoms than young or adult patients. Old age, male sex, and
hiatus hernia size greater than 3 cm are significantly associated with severe
esophagitis. Clinicians caring for older patients should be aware of the
nonspecific presentation and potential severity of reflux esophagitis in this
population.
PMID- 17038072
TI - Over-the-counter drug use by medicare beneficiaries in nursing homes:
implications for practice and policy.
AB - OBJECTIVES: To examine over-the-counter (OTC) medication use by Medicare
beneficiaries in nursing homes and to assess evidence of substitution of OTC
medications for prescription (Rx) medications by residents with no Rx coverage
and Medicaid. DESIGN: Cross-sectional multivariable analysis. SETTING: Medicare
beneficiaries included in the nationally representative Medicare Current
Beneficiary Survey in 2001. PARTICIPANTS: Seven hundred eighty-nine Medicare
beneficiaries with 1 or more months in a nursing home. MEASUREMENTS: Proportions
of residents using Rx and OTC medications per resident-month and counts of drugs
used within selected therapeutic classes. RESULTS: Study subjects were high users
of Rx (98%) and OTC (94%) drugs. The average resident was administered 8.8 unique
medications per month (5.9 Rx and 2.9 OTC medications). Twelve therapeutic
classes accounted for 93.9% of OTC medication use by residents, but Rx use was
also high in some of these same classes. For example, 70.3% of all subjects used
nonopioid OTC analgesics, and 19.0% used nonopioid Rx analgesics, and 13.8% used
OTC antacids/antiulcer agents, whereas 35.8% used Rx products in this class. The
highest overlap was in the category of cough and cold medications, of which 19.3%
used OTCs and 20.1% used Rx drugs. Multivariate regression analyses applied to
users of drugs in each these three therapeutic classes found no evidence that Rx
coverage influenced the choice of OTC versus Rx-only medications. CONCLUSION:
OTCs represent an important component of the therapeutic regimens of nursing home
residents, but utilization rates are insensitive to drug coverage. That may
change with the implementation of the Medicare Part D drug benefit.
PMID- 17038074
TI - Age-related macular degeneration: self-management and reduction of depressive
symptoms in a randomized, controlled study.
AB - OBJECTIVES: To assess the effectiveness of a self-management program for age
related macular degeneration (AMD) in reducing depressive symptoms. DESIGN:
Analysis of 6-month follow-up for a subset of participants in a randomized,
controlled trial who were clinically depressed at baseline. SETTING: University
ophthalmology clinic. PARTICIPANTS: Thirty-two depressed older adult volunteers
(mean age 81.5) with advanced AMD who had been randomized to a self-management
program (n=12) or one of two control conditions (n=20). Subjects were included if
at baseline they met criteria from the Structured Clinical Interview for the
Diagnostic and Statistical Manual of Mental Disorders, Axis, I, Fourth Edition,
Research Version, for major or minor depressive disorder with significant
depressive symptoms (>or=5 points) on the 15-item Geriatric Depression Scale (GDS
15). INTERVENTION: AMD self-management program consisting of cognitive and
behavioral elements including health education and enhancement of problem-solving
skills. MEASUREMENTS: Primary outcome measure was GDS-15. Secondary outcome
measures included National Eye Institute Visual Function Questionnaire (NEI-VFQ)
and AMD Self-Efficacy Questionnaire. RESULTS: At 6-month follow-up, the self
management group had a significantly greater reduction in depressive symptoms on
the GDS-15 than the controls (P=.03). The mean reduction of 2.92 points in the
self-management group was more than the 2-point change threshold considered to be
clinically meaningful. Change on the NEI-VFQ was nonsignificant. Reduction in
depressive symptoms was associated with greater self-efficacy in the self
management group. CONCLUSION: These findings may support the effectiveness of an
AMD self-management program for depressed older adults with advanced vision loss
from AMD.
PMID- 17038073
TI - Reducing suicidal ideation in depressed older primary care patients.
AB - OBJECTIVES: To determine the effect of a primary care-based collaborative care
program for depression on suicidal ideation in older adults. DESIGN: Randomized,
controlled trial. SETTING: Eighteen diverse primary care clinics. PARTICIPANTS:
One thousand eight hundred one adults aged 60 and older with major depression or
dysthymia. INTERVENTION: Participants randomized to collaborative care had access
to a depression care manager who supported antidepressant medication management
prescribed by their primary care physician and offered a course of Problem
Solving Treatment in Primary Care for 12 months. Participants in the control arm
received care as usual. MEASUREMENTS: Participants had independent assessments of
depression and suicidal ideation at baseline and 3, 6, 12, 18, and 24 months.
Depression was assessed using the Structured Clinical Interview for the
Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (SCID).
Suicidal ideation was determined using the SCID and the Hopkins Symptoms
Checklist. RESULTS: At baseline, 139 (15.3%) intervention subjects and 119
(13.3%) controls reported thoughts of suicide. Intervention subjects had
significantly lower rates of suicidal ideation than controls at 6 months (7.5% vs
12.1%) and 12 months (9.8% vs 15.5%) and even after intervention resources were
no longer available at 18 months (8.0% vs 13.3%) and 24 months (10.1% vs 13.9%).
There were no completed suicides in either group. Information on suicide attempts
or hospitalization for suicidal ideation was not available. CONCLUSION: Primary
care-based collaborative care programs for depression represent one strategy to
reduce suicidal ideation and potentially the risk of suicide in older primary
care patients.
PMID- 17038075
TI - To what extent do geriatricians document the most bothersome symptoms of patients
with advanced dementia?
AB - OBJECTIVES: To assess whether geriatricians documented the bothersome symptoms of
patients with advanced dementia, proxy reports of the most-bothersome symptoms
affecting those patients (as elicited in research interviews) were compared with
what geriatricians who had seen those patients in a proximate clinic visit
documented in the medical record. DESIGN: Retrospective chart review. SETTING:
Outpatient geriatrics clinic at the University of Chicago. PARTICIPANTS: Fifty
seven pairs of patients with dementia (Functional Assessment Staging Tool stage 6
or 7) and their proxies. MEASUREMENTS: Clinic notes were reviewed for
documentation of patients' bothersome symptoms that proxies reported during
research interviews. Proxy reports had been recorded in the previously
established Palliative Excellence in Alzheimer Care Efforts database. RESULTS:
The most-bothersome symptom was documented at least once in 84.2% (48/57) of
clinic notes. The second-most-bothersome symptom was documented in 70.3% (26/37)
of clinic notes. Most symptoms were documented in the Assessment and Plan section
of the note. CONCLUSION: Geriatricians identified and documented the vast
majority of bothersome symptoms, as reported by proxies, of patients with
moderate to severe dementia.
PMID- 17038076
TI - Satisfaction with end-of-life care for nursing home residents with advanced
dementia.
AB - OBJECTIVES: To identify factors associated with satisfaction with care for
healthcare proxies (HCPs) of nursing home (NH) residents with advanced dementia.
DESIGN: Cross-sectional study. SETTING: Thirteen NHs in Boston. PARTICIPANTS: One
hundred forty-eight NH residents aged 65 and older with advanced dementia and
their formally designated HCPs. MASUREMENTS: The dependent variable was HCPs'
score on the Satisfaction With Care at the End of Life in Dementia (SWC-EOLD)
scale (range 10-40; higher scores indicate greater satisfaction). Resident
characteristics analyzed as independent variables were demographic information,
functional and cognitive status, comfort, tube feeding, and advance care
planning. HCP characteristics were demographic information, health status, mood,
advance care planning, and communication. Multivariate stepwise linear regression
was used to identify factors independently associated with higher SWC-EOLD score.
RESULTS: The mean ages+/-standard deviation of the 148 residents and HCPs were
85.0+/-8.1 and 59.1+/-11.7, respectively. The mean SWC-EOLD score was 31.0+/-4.2.
After multivariate adjustment, variables independently associated with greater
satisfaction were more than 15 minutes discussing advance directives with a care
provider at the time of NH admission (parameter estimate=2.39, 95% confidence
interval (CI)=1.16-3.61, P<.001), greater resident comfort (parameter
estimate=0.10, 95% CI=0.02-0.17, P=.01), care in a specialized dementia unit
(parameter estimate=1.48, 95% CI=0.25-2.71, P=.02), and no feeding tube
(parameter estimate=2.87, 95% CI=0.46-5.25, P=.02). CONCLUSION: Better
communication, greater resident comfort, no tube feeding, and care in a
specialized dementia unit are modifiable factors that may improve satisfaction
with care in advanced dementia.
PMID- 17038077
TI - Cariogenic bacteria and caries risk in elderly Japanese aged 80 and older with at
least 20 teeth.
AB - OBJECTIVES: To assess caries risk and check the presence of four commonly found
oral cariogenic bacteria in "8020" achievers. DESIGN: Initial report based on
Japan's newly implemented "8020" campaign, which aims to promote health and
awareness in older people. Simply stated, the goal is, at 80 years, to maintain
20 teeth. SETTING: Healthy community-dwelling elderly individuals of Okayama
Prefecture, Japan. PARTICIPANTS: One hundred sixty individuals aged 80 and older
with 20 of their own natural teeth. MEASUREMENTS: General and oral health
conditions, caries risk assessment using the Cariostat method, and polymerase
chain reaction (PCR) detection of four oral cariogenic bacteria. RESULTS: The
participants had an average of 24.7 teeth, of which 12.1 were sound, 12.2 were
treated, and 0.4 were untreated. Based on Cariostat scores, 64.4% had low caries
risk. Using PCR, Streptococcus mutans, S. sobrinus, Lactobacillus casei, and L.
plantarum were detected in 51.3%, 23.1%, 40%, and 25% of the participants,
respectively. S. mutans (P<.001), S. sobrinus (P=.002), L. casei (P<.001), and L.
plantarum (P=.001) deoxyribonucleic acid band was detected more in participants
with high caries risk scores. CONCLUSION: Participants with low caries risk
scores had low prevalence of cariogenic bacteria, 20 or more sound teeth, and
fewer missing teeth. Incorporating caries risk assessment, using the Cariostat
and PCR analysis, in the "8020" campaign in health systems worldwide will
contribute to a better life for the aging society, initiate research interest
regarding the program, and improve current health policies.
PMID- 17038078
TI - Preoperative risk assessment for delirium after noncardiac surgery: a systematic
review.
AB - Delirium is a common postoperative complication in older adults associated with
adverse events including functional decline, longer lengths of stay, and risk of
institutionalization. The purpose of this article is to systematically review
preoperative risk factors associated with delirium following noncardiac surgery.
A medical literature search was conducted using several bibliographic databases
(PubMed, CINAHL, Cochrane, PsychInfo), supplemented by a manual search of the
references of retrieved articles. Studies were retained for review after meeting
strict inclusion criteria that included only operative patients with incident
postoperative delirium diagnosed prospectively using criteria derived from the
Diagnostic and Statistical Manual of Mental Disorders Third or Fourth Edition.
Quantitative analyses included significance testing, homogeneity testing, and
effect-size pooling. Twenty-five articles were included for review. The incidence
of delirium ranged from 5.1% to 52.2%, with greater rates after hip fracture and
aortic surgeries. This review found two scales, a clinical prediction rule, and a
delirium risk classification system that were validated in other operative
settings. Individual risk factor analysis suggested that cognitive impairment,
older age, functional impairment, sensory impairment, depression, preoperative
psychotropic drug use, psychopathological symptoms, institutional residence, and
greater comorbidity were associated with postoperative delirium. Of the risk
factors examined, evidence was most robust for an association between delirium
and cognitive impairment or psychotropic drug use, with moderate effect sizes for
both. Missing data and measurement differences did not allow for inferences to be
made about other risk factors. Effect-size pooling supports the concept that
delirium is a heterogeneous disorder with multiple risk factors. More research is
needed to better identify patients at risk for postoperative delirium and to
develop preventive strategies.
PMID- 17038079
TI - Traumatic brain injury in older adults: epidemiology, outcomes, and future
implications.
AB - Traumatic brain injury (TBI) is a significant problem in older adults. In persons
aged 65 and older, TBI is responsible for more than 80,000 emergency department
visits each year; three-quarters of these visits result in hospitalization as a
result of the injury. Adults aged 75 and older have the highest rates of TBI
related hospitalization and death. Falls are the leading cause of TBI for older
adults (51%), and motor vehicle traffic crashes are second (9%). Older age is
known to negatively influence outcome after TBI. Although geriatric and
neurotrauma investigators have identified the prognostic significance of
preadmission functional ability, comorbidities, sex, and other factors such as
cerebral perfusion pressure on recovery after illness or injury, these variables
remain understudied in older adults with TBI. In the absence of good clinical
data, predicting outcomes and providing care in the older adult population with
TBI remains problematic. To address this significant public health issue, a
refocusing of research efforts on this population is justified to prevent TBI in
the older adult and to discern unique care requirements to facilitate best
patient outcomes.
PMID- 17038080
TI - Clinical characteristics and longitudinal changes of informal cost of Alzheimer's
disease in the community.
AB - Most estimates of the cost of informal caregiving in patients with Alzheimer's
disease (AD) remain cross-sectional. Longitudinal estimates of informal
caregiving hours and costs are less frequent and are from assessments covering
only short periods of time. The objectives of this study were to estimate long
term trajectories of the use and cost of informal caregiving for patients with AD
and the effects of patient characteristics on the use and cost of informal
caregiving. The sample is drawn from the Predictors Study, a large, multicenter
cohort of patients with probable AD, prospectively followed annually for up to 7
years in three university-based AD centers in the United States (n=170).
Generalized linear mixed models were used to estimate the effects of patient
characteristics on use and cost of informal caregiving. Patients' clinical
characteristics included cognitive status (Mini-Mental State Examination),
functional capacity (Blessed Dementia Rating Scale (BDRS)), comorbidities,
psychotic symptoms, behavioral problems, depressive symptoms, and extrapyramidal
signs. Results show that rates of informal care use and caregiving hours (and
costs) increased substantially over time but were related differently to
patients' characteristics. Use of informal care was significantly associated with
worse cognition, worse function, and higher comorbidities. Conditional on
receiving informal care, informal caregiving hours (and costs) were mainly
associated with worse function. Each additional point on the BDRS increased
informal caregiving costs 5.4%. Average annual informal cost was estimated at
$25,381 per patient, increasing from $20,589 at baseline to $43,030 in Year 4.
PMID- 17038081
TI - Are internal medicine residency programs adequately preparing physicians to care
for the baby boomers? A national survey from the Association of Directors of
Geriatric Academic Programs Status of Geriatrics Workforce Study.
AB - Patients aged 65 and older account for 39% of ambulatory visits to internal
medicine physicians. This article describes the progress made in training
internal medicine residents to care for older Americans. Program directors in
internal medicine residency programs accredited by the Accreditation Council for
Graduate Medical Education were surveyed in the spring of 2005. Findings from
this survey were compared with those from a similar 2002 survey to determine
whether any changes had occurred. A 60% response rate was achieved (n=235). In
these 3-year residency training programs, 20 programs (9%) required less than 2
weeks of clinical instruction that was specifically structured to teach geriatric
care principles, 48 (21%) at least 2 weeks but less than 4 weeks, 144 (62%) at
least 4 weeks but less than 6 weeks, and 21 (9%) required 6 or more weeks. As in
2002, internal medicine residency programs continue to depend on nursing home
facilities, geriatric preceptors in nongeriatric clinical ambulatory settings,
and outpatient geriatric assessment centers for their geriatrics training.
Training was most often offered in a block format. The mean number of physician
faculty per residency program dedicated to teaching geriatric medicine was 3.5
full-time equivalents (FTEs) (range 0-50), compared with a mean of 2.2 FTE
faculty in 2002 (P 25 kg m(-2)) obtained across
all ethnic groups in the adult population in 1998, were 57% for women and 29% for
men. From the 1960s until the late 1980s, the notion of 'healthy' or 'benign'
obesity was propagated in South Africa. Not surprisingly, this led to ignorance
around the problem of obesity, and treatment of some of the comorbid diseases was
neglected. Fortunately, as an increasing number of seminal studies draw us closer
to reality, the misperception of benign obesity is being corrected. This is
allowing us to address the real issues underlying the current epidemic, and to
recognize and manage the comorbid diseases, in particular type 2 diabetes. A new
framework for research is also emerging as we begin to define the factors
underlying the impact of ethnicity on obesity.
PMID- 17038126
TI - The management of osteoarthritis in the obese patient: practical considerations
and guidelines for therapy.
AB - Obesity and osteoarthritis (OA) co-exist in an increasing part of the population.
The two diseases intertwine in several ways. The evolution in the population
shows a tendency towards deterioration of both by increasing general age and
weight. The two diseases share pathogenetic features and the development of one
disease increases the risk of the other and may be the onset of a vicious circle.
There is a link between treatments of these two diseases as well. There is now
solid (gold) evidence that by treating effectively the obesity of patients with
co-occurring OA, the functional status is dramatically ameliorated; the short
term results are equal to that of a joint replacement. The long-term efficacy of
a weight loss remains to be shown. OA is definitely one of many diseases in which
obesity must be taken seriously into account when planning a correct treatment of
patients. The regimens used in the controlled studies of such patients are
reviewed and it may be concluded that practical aspects of the dietary
intervention in obese patients with OA are not different from general
recommendations.
PMID- 17038127
TI - Obesity and prognosis of breast cancer.
AB - Obesity has a complicated relationship to both breast cancer risk and the
clinical behaviour of the established disease. It is suggested that obesity is
associated with both an increased risk of developing breast cancer risk and worse
prognosis after disease onset. In post-menopausal women, various measures of
obesity such as body mass index, weight, weight gain and waist : hip ratio have
all been positively associated with risk of developing breast cancer. In most but
not all case-control and prospective cohort studies, an inverse relationship has
been found between weight and breast cancer among pre-menopausal women. Some data
suggest that adult weight gain and central obesity increase the risk of pre
menopausal breast cancer. Obesity at the time of diagnosis is thought to be
significant as a poor prognostic factor. Obesity is associated with adverse
outcomes in both pre- and post-menopausal women with breast cancer. Many cancer
survivors seek ways to minimize the risk of recurrence and death because of
breast cancer. Despite complex and at times controversial data, enough evidence
is available at present to suggest that weight management should be a part of the
strategy to prevent the occurrence, recurrence and death because of breast
cancer. In this review the effect of obesity on the prognosis of breast cancer is
examined in detail.
PMID- 17038128
TI - Obesity and disability - a short review.
AB - The prevalence of both obesity and disability is increasing globally and there is
now growing evidence to suggest that these two health priorities may be linked.
This paper explores the evidence linking obesity to muscular-skeletal conditions,
mental health disorders and learning disabilities in both adult and child
populations. The impact of obesity on the four most prevalent disabling
conditions in the UK (arthritis, mental health disorders, learning disabilities
and back ailments) has been examined through novel data analysis of the 2001
Health Survey for England and UK Back Exercise And Manipulation trial data.
Together these analyses strongly suggest that whether the cause or result of
disability, obesity is undeniably implicated, thus presenting a serious public
health priority. Future research efforts are required to strengthen the evidence
base examining obesity in back disorders, mental health and learning
disabilities, in order to improve current clinical management.
PMID- 17038129
TI - An overview of obesity-specific quality of life questionnaires.
AB - The measurement of quality of life in patients with obesity is useful to evaluate
the effects of treatment (including bariatric surgery) and may influence the
development of clinical pathways, service provision, healthcare expenditures and
public health policy. Consequently, clinicians, researchers and policy makers
must rely on valid measurement instruments. We reviewed 11 obesity-specific
quality of life questionnaires and classified them according to their domain of
interest and described their measurement properties (specifications, validity,
reliability, responsiveness and interpretability). We found that (i) nine
questionnaires were developed specifically to be used as evaluative instruments
in clinical trials; (ii) only three targeted populations with morbid obesity
(body mass index > 40 kg m(-2)); (iii) construct validity was properly studied in
three questionnaires; (iv) demonstration of responsiveness from independent
randomized controlled trials was available for two of the 11 questionnaires; (v)
keys to interpretation of scores were provided for three questionnaires. Future
research should include further validation and a better definition of the
interpretability of existing instruments.
PMID- 17038130
TI - How much may I eat? Calorie estimates based upon energy expenditure prediction
equations.
AB - How much may I eat? Most healthcare workers, when asked this question, have
insufficient knowledge to educate their patients on a healthy energy intake
level. In this review we examine the available methods for estimating adult
energy requirements with a focus on the newly developed National Academy of
Sciences/Institute of Medicine (NAS/IOM) doubly-labelled water total energy
expenditure (TEE) prediction equations. An overview is first provided of the
traditional factorial method of estimating energy requirements. We then extend
this overview by exploring the development of the NAS/IOM TEE prediction models
and their role in estimating energy requirements as a function of sex, age,
weight, height and physical activity level. The NAS/IOM prediction models were
developed for evaluating group energy requirements, although the formulas can be
applied in individual 'example' patients for educational purposes. Potential
limitations and interpretation issues of both the factorial and NAS/IOM methods
are examined. This information should provide healthcare professionals with the
tools and understanding to appropriately answer the question, 'How much may I
eat?'
PMID- 17038131
TI - Carl von Linne (1707-1778).
PMID- 17038133
TI - Pacemaker diagnosis of sleep disordered breathing.
PMID- 17038134
TI - Feasibility of automated detection of advanced sleep disordered breathing
utilizing an implantable pacemaker ventilation sensor.
AB - OBJECTIVES: This study tested the feasibility of automatically detecting advanced
sleep disordered breathing (SDB) from a pacemaker trans-thoracic impedance
sensor. BACKGROUND: SDB is prevalent yet under-diagnosed in patients with
cardiovascular disease. The potential for automated detection of SDB in patients
receiving pacemakers with respiration sensors has not been fully explored. We
hypothesized that the trans-thoracic impedance sensor could be utilized for
automatic detection of advanced SDB. METHODS: Patients underwent overnight
polysomnography (PSG). The pacemaker trans-thoracic impedance signal was
simultaneously recorded and time synchronized with the polysomnograph.
Cardiovascular health variables were abstracted from medical records. Apnea was
defined as cessation of inspiratory airflow lasting 10 seconds or longer.
Hypopnea was defined as a reduction of tidal volume of at least 30% from baseline
tidal volume, lasting 10 seconds or more. A computer algorithm (PM-A) was
developed to automatically detect SDB from the pacemaker impedance sensor data.
The performance of automated SDB detection was compared against PSG. RESULTS:
Sixty patients (aged 69 +/- 12 years, 45 males) were studied. Advanced SDB
(moderate or severe) was diagnosed in 40 patients. Severe SDB (apnea-hypopnea
index [AHI]> or = 30) was diagnosed in 32 patients (53%), but only 5 patients had
prior diagnosis of the disease. Moderate SDB (30 > AHI > 15) was diagnosed in 8
patients of whom only two were previously diagnosed. Cardiovascular health
variables did not predict the presence of advanced SDB. PM-A derived AHI
correlated with that of the PSG (r = 0.80, P < 0.01). The algorithm identified
patients with advanced SDB with 82% sensitivity and 88% specificity. CONCLUSIONS:
It is feasible to automatically measure SDB severity using a pacemaker trans
thoracic impedance sensor. Advanced SDB was frequently undiagnosed in this cohort
of pacemaker patients.
PMID- 17038135
TI - Pacemaker longevity: are we getting what we are promised?
AB - BACKGROUND: Although pacemaker manufacturers provide projections on longevity,
these projections cannot be relied upon due to the assumptions of output
parameters being far in excess of those programmed in clinical practice.
OBJECTIVE: The purpose of this review was to compare the actual longevity to the
calculated longevity of pacemakers based on battery cell characteristics taking
into account individual programmed parameters, mode, degree of usage, and percent
pacing. This was also compared to the manufacturers' own projected longevities.
METHODS: Patients who had a pacemaker replaced between 1998 and 2003 were
included (n = 124). Cell characteristics were obtained from manufacturers and
programmed parameters were obtained at each visit. Stepwise calculations were
done for each visit to find current drain during each interval, and then were
used in a weighted average to find the total average lifetime current drain. This
was subsequently used to find a calculated longevity for each pacemaker to be
compared to the actual longevity observed. RESULTS: The pacemakers lasted 491+/
92 days (mean+/-SEM) less than calculated. There was also a difference between
dual- and single-chamber devices (though not statistically significant).
Moreover, it was found that there were significant differences between
manufacturers. CONCLUSIONS: There appears to be a significant discrepancy between
calculated and actual longevities, confirming that battery depletion occurs
earlier than expected. This suggests that current drain expended for ancillary
functions may be considerable. Another factor may be pre-implantation drain.
Vigilance with programming of outputs, modes, sensors, heart rates, and ancillary
functions could potentially extend longevity and postpone/obviate the need for
costly repeat surgery with its attended risk of complications. Furthermore, the
differences between manufacturers seem to parallel the clinical impressions.
PMID- 17038136
TI - Right ventricular outflow tract pacing: practical and beneficial. A 9-year
experience of 460 consecutive implants.
AB - BACKGROUND: Pacing from the right ventricular apex (RVA) in patients with
ventricular dysfunction has been identified as a possible contributor to
deterioration of ventricular function. Therefore, alternative pacing sites such
as the right ventricular outflow tract (RVOT) are receiving intensified scrutiny.
An unresolved question is whether technical, procedural, and stability issues are
comparable for the RVA and the RVOT. METHODS: This report details 460 consecutive
ventricular pacing lead implants with the primary intended site in the RVOT.
Patients were evaluated for success, complication rates, and followed-up for
stability of pacing parameters. The total patient implant population included 300
male and 170 female patients with a mean age of 70.6 years. Ten patients were
excluded from the analysis, since there was a primary indication and intention to
implant in the RVA, leaving a total of 460 patients for analysis. The indications
for pacing were symptomatic bradycardia due to any cause and/or Mobitz II or
complete heart block. There was no clinical evidence of heart failure in 420
patients. In 40 patients with heart failure, the indication for pacing was
cardiac resynchronization therapy using the RVOT as an alternate site when pacing
from a branch vein of the coronary sinus was not possible. Outcome information
was obtained from the implanter's clinic. RESULTS: The overall success rate in
the RVOT was 84% over the total 9-year period with a 92% success rate in the last
4(1/2) years, using the RVOT technique described. At 20 months in a subgroup
comparison of RVOT and RVA implants, there was no significant difference in
pacing threshold, R-wave sensing, or pacing lead impedance. Dislodgment occurred
in only 1 of 460 patients. Reasons for failure to implant in the RVOT include
inability to find a stable position with adequate pacing and sensing thresholds
(related to anatomy, scarred myocardium, pulmonary hypertension, tricuspid
regurgitation), hemodynamic instability limiting time for implant, and a learning
curve. Long-term stability and lead performance were excellent, and certain acute
and chronic complications of RV pacing did not occur.
PMID- 17038137
TI - Right ventricular outflow tract pacing: radiographic and electrocardiographic
correlates of lead position.
AB - OBJECTIVE: To characterize the pacing site in an unselected series of patients
undergoing right ventricular outflow tract (RVOT) lead placement and investigate
the role of the electrocardiogram (ECG) in predicting implantation. BACKGROUND:
Right ventricular apical pacing is associated with long-term adverse effects on
left ventricular function, fuelling interest in alternative pacing sites,
especially the RVOT. Previous studies have been conflicting, possibly due to poor
definition of pacing site within the RVOT. METHODS: In 150 patients undergoing
pacemaker implantation, implanters were asked to place the lead in the RVOT.
Radiographs were performed in the antero-posterior (AP) and 40 degrees right and
left anterior-oblique projections post procedure. Fifty-six had left lateral
radiographs. Lead position was categorized using AP/RAO (right anterior oblique)
to confirm RVOT placement and left anterior oblique to distinguish free wall from
septum. A 12-lead ECG was performed during ventricular pacing. RESULTS: Leads
were below the RVOT in 18. Of the remaining 132, the majority (94%) were in the
inferior/low RVOT. Eighty-one out of 132 were septal and 51 free wall. Septal
sites were associated with shorter QRS duration (134 ms vs 143 ms, P < 0.02).
Free wall sites displayed more frequent notching of the inferior leads (P <
0.01). A negative deflection in lead I provided a positive predictive value of
90% for septal sites. In those with lateral radiographs, a posteriorly projected
lead was 100% specific for septal placement. CONCLUSIONS: This study demonstrates
the heterogeneity of lead placement within the RVOT. Septal and free wall sites
display characteristic ECG patterns which may be used to aid placement. The left
lateral radiograph is useful in confirming a true septal location.
PMID- 17038138
TI - Does RV lead positioning provide additional benefit to cardiac resynchronization
therapy in patients with advanced heart failure?
AB - BACKGROUND AND OBJECTIVES: The left ventricular (LV) stimulation site is
currently recommended to position the lead at the lateral wall. However, little
is known as to whether right ventricular (RV) lead positioning is also important
for cardiac resynchronization therapy. This study compared the acute hemodynamic
response to biventricular pacing (BiV) at two different RV stimulation sites: RV
high septum (RVHS) and RV apex (RVA). METHODS AND RESULTS: Using micro-manometer
tipped catheter, LV pressure was measured during BiV pacing at RV (RVA or RVHS)
and LV free wall in 33 patients. Changes in LV dP/dt(max) and dP/dt(min) from
baseline were compared between RVA and RVHS. BiV pacing increased dP/dt(max) by
30.3 +/- 1.2% in RVHS and by 33.3 +/- 1.7% in RVA (P = n.s.), and decreased
dP/dt(min) by 11.4 +/- 0.7% in RVHS and by 13.0 +/- 1.0% in RVA (P = n.s.). To
explore the optimal combination of RV and LV stimulation sites, we assessed
separately the role of RV positioning with LV pacing at anterolateral (AL),
lateral (LAT), or posterolateral (PL) segment. When the LV was paced at AL or
LAT, the increase in dP/dt(max) with RVHS pacing was smaller than that with RVA
pacing (AL: 12.2 +/- 2.2% vs 19.3 +/- 2.1%, P < 0.05; LAT: 22.0 +/- 2.7% vs 28.5
+/- 2.2%, P < 0.05). There was no difference in dP/dt(min) between RVHS- and RVA
pacing in individual LV segments. CONCLUSIONS: RVHS stimulation has no overall
advantage as an alternative stimulation site for RVA during BiV pacing. RVHS was
equivalent with RVA in combination with the PL LV site, while RVA was superior to
RVHS in combination with AL or LAT LV site.
PMID- 17038139
TI - Effect of percutaneous interventions within the coronary sinus on the success
rate of the implantations of resynchronization pacemakers.
AB - BACKGROUND: Cardiac resynchronization therapy (CRT) becomes a "gold standard" in
therapy of selected patients with advanced heart failure. We set out to evaluate
the feasibility and safety of percutaneous interventions within coronary sinus
(CS) and their effect on the success rate of left ventricular (LV) lead
implantation during CRT. METHODS: The study analyzed eight consecutive patients
with the indications for CRT, who needed additional procedures within CS to
overcome technical problems during left ventricular (LV) electrode implantation.
The analyzed group consisted of three subgroups: patients in whom percutaneous
balloon angioplasty within CS was needed (n = 4); patients with acute instability
of the lead, requiring stenting of the vein to fix the electrode (n = 2); and
patients with the stenting of CS due to late dislocation of the lead (n = 2).
Success rate, procedure duration, fluoroscopy, complications, and electrical
parameters of leads were analyzed. RESULTS: Success rate of the procedures was
87.5%; additional interventions increased overall efficacy of CRT implantation at
our center from 88% to 98% (P < 0.05). Procedure duration (155.0 minute) and
fluoroscopy time (42.5 minute) remained acceptable for the patient and operator;
however, both were higher than in the procedures performed routinely in our
hospital. Electrical properties of the LV leads were stable and within normal
ranges during the observation period. We noted two local dissections of CS during
the procedure, which remained clinically silent. CONCLUSION: Percutaneous
interventions within CS seem to be feasible and safe treatment options, which can
improve the short- and long-term success rates of CRT.
PMID- 17038140
TI - Atrioventricular junction ablation followed by resynchronization therapy in
patients with congestive heart failure and atrial fibrillation (AVERT-AF) study
design.
AB - Atrial fibrillation (AF) and congestive heart failure (CHF) affect millions of
patients in the United States. Several studies suggest that AF and in particular
the irregular ventricular response might be contributing to the left ventricular
dysfunction. Studies that compared pharmacologic rate control to atrioventricular
junction (AVJ) ablation followed by right ventricular pacing which restores a
regular ventricular response, failed to show an improvement when compared to
pharmacological rare control. These results might be explained by the fact that
while AVJ ablation restored a regular ventricular response, it subjected patients
to the detrimental effects of RV apical pacing. The AVERT-AF trial (Atrio
VEntricular Junction Ablation Followed by Resynchronization Therapy in patients
with CHF and AF) is a prospective, randomized, double-blinded, multicenter trial
that will be testing the hypothesis that AVJ ablation followed by biventricular
pacing significantly improves exercise capacity and functional status compared to
pharmacologic rate control in patients with chronic AF and depressed ejection
fraction, regardless of rate or QRS duration. A total of 180 patients will be
enrolled to test the primary endpoint, which is exercise duration.
Patients_enrollment will begin in summer 2006 and is expected to be completed in
2008. The results of this trial should help define the best treatment option for
this common arrhythmia in patients with left ventricular dysfunction.
PMID- 17038141
TI - Signal-averaged P wave reflects change in atrial electrophysiological substrate
afforded by verapamil following cardioversion from atrial fibrillation.
AB - BACKGROUND: Detailed analysis of signal-averaged P waves (SAPW) can provide
insights into atrial electrophysiology. Abbreviated dosing of verapamil prior to
cardioversion improves outcome at 1 week postcardioversion. The mechanism by
which verapamil manifests benefit is uncertain. We hypothesized the SAPW would
reflect any change in atrial electrophysiologic substrate afforded by verapamil
when compared with controls. METHODS: We investigated 23 patients attending
external cardioversion of persistent atrial fibrillation (AF) (6 female; mean age
68 years). Patients were randomized to verapamil 240 mg daily in three divided
doses 3 days before cardioversion and 1 week after, or usual medication. SAPW
recordings were performed during sinus rhythm (SR) immediately after
cardioversion, at 24 hours and 1 week. RESULTS: The groups were comparable in
terms of age, gender, left atrial size, and duration of AF. Eight of nine
patients prescribed verapamil maintained SR at 1 week postcardioversion compared
with 6 of 14 controls (P = 0.027). SAPW spectral analysis delivered higher energy
for patients prescribed verapamil (median (IQ range)); 40.8 (33.4-95.1) versus
25.7 (19.0-38.0) for energy within 20-150 Hz, P20 (microV(2)x s; P = 0.03). There
was no difference in P-wave duration (PWD) or root mean square of the terminal 30
ms between the two groups. Early reinitiation occurred in patients with
significantly lower P-wave energy 19.6 (12.9-24.6) versus 39.9 (24.0-47.0) (P =
0.017). CONCLUSIONS: Verapamil 240 mg daily for 3 days prior to cardioversion and
1 week after reduces early recurrence of AF. The SAPW observations indicate
change in atrial electrophysiologic substrate might be responsible for benefit
afforded by verapamil.
PMID- 17038142
TI - Decremental ramp atrial extrastimuli pacing protocol for the induction of
atrioventricular nodal re-entrant tachycardia and other supraventricular
tachycardias.
AB - AIM: The primary aim of this study was to evaluate the utility of decremental
ramp atrial extrastimuli pacing protocol (PRTCL) for induction of
atrioventricular nodal re-entrant tachycardia (AVNRT), and other supraventricular
tachycardias (SVTs), compared to standard (STD) methods. METHODS: The study
cohort of 121 patients (age 57.51 +/- 14.02 years) who presented with documented
SVTs and/or symptoms of palpitations and dizziness, and underwent invasive
electrophysiological evaluation was divided into Group I (AVNRT, n = 42) and
Group II (Control, n = 79). The PRTCL involved a train of six atrial
extrastimuli, delivered in a decremental ramp fashion. The STD methods included
continuous burst and rapid incremental pacing up to atrioventricular (AV) block
cycle length, and single and occasionally double atrial extrastimuli.
Prolongation in the Atrio-Hisian (Delta-AH) intervals achieved by both methods
were compared, as were induction frequencies. RESULTS: In Group I, three
categories of responses--(1) induction of AVNRT, (2) induction of echo beats
only, and (3) none--were observed in 29 (69%), 11 (26%), and 2 (5%) patients with
the PRTCL, when compared with 14 (33%), 16 (38%), and 12 (29%) patients with STD
methods in the baseline state without the use of pharmacological agents. The
Delta-AH intervals for each of these three categories were larger using PRTCL
versus STD methods; 293.3 +/- 95.2 ms versus 192.9 +/- 61.4 ms (P < 0.005), 308.6
+/- 68.5 ms versus 189. 9 +/- 64.9 ms (P < 0.0005), and 203.0 +/- 86.3 ms versus
145.8 +/- 58.9 ms (P = NS), respectively. In Group II, in one patient with dual
AV nodal physiology but no clinical tachycardia, the PRTCL induced nonsustained
(12 beats) AVNRT. Additionally, in this group, both PRTCL and STD methods induced
atrial tachycardia in two patients and orthodromic AV re-entrant tachycardia in
one patient. CONCLUSION: Decremental ramp atrial extrastimuli pacing PRTCL
demonstrates a superior response for induction of typical AVNRT as compared to
STD techniques. Because of easy and reliable induction of AVNRT and echo beats by
the PRTCL, we recommend it as a method to increase the likelihood of induction of
AVNRT. For induction of other SVTs, the PRTCL and the STD methods are comparable.
PMID- 17038143
TI - The electrophysiological characteristics in patients with ventricular stimulation
inducible fast-slow form atrioventricular nodal reentrant tachycardia.
AB - BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) can usually be
induced by atrial stimulation. However, it seldom may be induced with only
ventricular stimulation, especially the fast-slow form of AVNRT. The purpose of
this retrospective study was to investigate the specific electrophysiological
characteristics in patients with the fast-slow form of AVNRT that could be
induced with only ventricular stimulation. METHODS: The total population
consisted of 1,497 patients associated with AVNRT, and 106 (8.4%) of them had the
fast-slow form of AVNRT and 1,373 (91.7%) the slow-fast form of AVNRT. In
patients with the fast-slow form of AVNRT, the AVNRT could be induced with only
ventricular stimulation in 16 patients, Group 1; with only atrial stimulation or
both atrial and ventricular stimulation in 90 patients, Group 2; and with only
atrial stimulation in 13 patients, Group 3. We also divided these patients with
slow-fast form AVNRT (n = 1,373) into two groups: those that could be induced
only by ventricular stimulation (Group 4; n = 45, 3%) and those that could be
induced by atrial stimulation only or by both atrial and ventricular stimulation
(n = 1.328, 97%). RESULTS: Patients with the fast-slow form of AVNRT that could
be induced with only ventricular stimulation had a lower incidence of an
antegrade dual AVN physiology (0% vs 71.1% and 92%, P < 0.001), a lower incidence
of multiple form AVNRT (31% vs 69% and 85%, P = 0.009), and a more significant
retrograde functional refractory period (FRP) difference (99 +/- 102 vs 30 +/- 57
ms, P < 0.001) than those that could be induced with only atrial stimulation or
both atrial and ventricular stimulation. The occurrence of tachycardia stimulated
with only ventricular stimulation was more frequently demonstrated in patients
with the fast-slow form of AVNRT than in those with the slow-fast form of AVNRT
(15% vs 3%, P < 0.001). Patients with the fast-slow form of AVNRT that could be
induced with only ventricular stimulation had a higher incidence of retrograde
dual AVN physiology (75% vs 4%, P < 0.001), a longer pacing cycle length of
retrograde 1:1 fast and slow pathway conduction (475 +/- 63 ms vs 366 +/- 64 ms,
P < 0.001; 449 +/- 138 ms vs 370 +/- 85 ms, P = 0.009), a longer retrograde
effective refractory period of the fast pathway (360 +/- 124 ms vs 285 +/- 62 ms,
P = 0.003), and a longer retrograde FRP of the fast and slow pathway (428 +/- 85
ms vs 362 +/- 47 ms, P < 0.001 and 522 +/- 106 vs 456 +/- 97 ms, P = 0.026) than
those with the slow-fast form of AVNRT that could be induced with only
ventricular stimulation. CONCLUSION: This study demonstrated that patients with
the fast-slow form of AVNRT that could be induced with only ventricular
stimulation had a different incidence of the antegrade and retrograde dual AVN
physiology and the specific electrophysiological characteristics. The mechanism
of the AVNRT stimulated only with ventricular stimulation was supposed to be
different in patients with the slow-fast and fast-slow forms of AVNRT.
PMID- 17038144
TI - Spatial distribution of repolarization and depolarization abnormalities evaluated
by body surface potential mapping in patients with Brugada syndrome.
AB - BACKGROUND: Mutations in sodium channel gene, SCN5A, have been identified in
Brugada syndrome, but it is still unclear as to how sodium channel dysfunction
relates to arrhythmogenesis. We examined spatial distribution of both
repolarization and depolarization abnormalities in patients with Brugada syndrome
by using 87-leads body surface potential mapping (BSPM). METHODS: BSPM was
recorded under baseline condition and after pharmacological interventions in 28
patients with Brugada syndrome (27 males, 49 +/- 14 years). The ST-segment
amplitude 20 ms after the end of QRS (ST20), QRS duration, and corrected recovery
time (RTc) were measured in all 87-leads, and averaged among 6-leads (D-F, 5-6)
reflecting right ventricular outflow tract (RVOT) potentials and the other 81
leads. RESULTS: The ST20 was elevated at baseline, normalized by isoproterenol,
and augmented by pilsicainide in only the RVOT. The RTc was longer at baseline
and increased by pilsicainide in only the RVOT. On the other hand, the QRS
duration was slightly widened at baseline, further increased by pilsicainide, but
not changed by isoproterenol in both leads. CONCLUSIONS: The ST-segment elevation
and the RTc prolongation were localized and modulated by agents only in the RVOT
region, while the slight QRS widening at baseline and further increase by
pilsicainide were observed homogeneously. Our data suggest that depolarization
abnormalities are distributed homogeneously, whereas repolarization abnormalities
are localized in the RVOT.
PMID- 17038145
TI - Ventricular repolarization and heart rate responses during cardiovascular
autonomic function testing in LQT1 subtype of long QT syndrome.
AB - BACKGROUND: In the most prevalent LQT1 form of inherited long QT syndrome
symptoms often occur during abrupt physical or emotional stress. Sympathetic
stimulation aggravates repolarization abnormalities in experimental LQT1 models.
We hypothesized that autonomic function tests might reveal the abnormal
repolarization in asymptomatic LQT1 patients. METHODS: We measured heart rates
(HRs) and QT intervals in nine asymptomatic carriers of a C-terminal KCNQ1
mutation and 8 unaffected healthy subjects using an approach of global QT values
derived from 28 simultaneous electrocardiographic leads on beat-to-beat base
during Valsalva maneuver, mental stress, sustained handgrip, and light supine
exercise. RESULTS: LQT1 patients exhibited impaired shortening of both QTpeak and
QTend intervals during autonomic interventions but exaggerated lengthening of the
intervals--a QT overshoot--during the recovery phases. The number of tests with a
QT overshoot was 2.4 +/- 1.7 in LQT1 patients and 0.8 +/- 0.7 in unaffected
subjects (P = 0.02). Valsalva strain prolonged T wave peak to T wave end interval
(TPE) in LQT1 but not in unaffected patients. LQT1 patients showed diminished HR
acceleration in response to adrenergic challenge whereas HR responses to vagal
stimuli were similar in both groups. CONCLUSIONS: Standard cardiovascular
autonomic provocations induce a QT interval overshoot during recovery in
asymptomatic KCNQ1 mutation carriers. Valsalva maneuver causes an exaggerated
fluctuation of QT and TPE intervals partly explaining the occurrence of cardiac
events during abrupt bursts of autonomic activity in LQT1 patients.
PMID- 17038147
TI - Syncope in adults: terminology, classification, and diagnostic strategy.
AB - Syncope is a relatively common clinical syndrome that is a subset of a broader
range of conditions that cause transient loss of consciousness (TLOC). Other TLOC
conditions include seizures, concussions, and intoxications. However, despite
frequent confusion in the medical literature, syncope is and should be clearly
distinguished from those other causes of TLOC by virtue of its pathophysiology;
specifically, syncope is the result of self-terminating inadequacy of global
cerebral nutrient perfusion, while the other forms of TLOC have different
etiologies. Unfortunately, the diagnostic evaluation of syncope remains for the
most part poorly managed and inefficient. Careful history-taking, physical
examination, and judicious use of tests can not only increase the diagnostic
yield of the evaluation, but also increase patient safety and reduced overall
healthcare costs.
PMID- 17038148
TI - Acute subclavian or axillary vein occlusion during biventricular pacemaker
implantation.
AB - During biventricular pacemaker implantation, multiple punctures of the subclavian
vein were performed and venous occlusion was apparent during the procedure, which
in one case was stopped before lead insertion and in the other patient new access
has to be forced through the occlusion by removing one of the already implanted
leads. For implanting physicians, it is important to know that acute venous
occlusion may occur during lead implantation.
PMID- 17038149
TI - Lead interaction: rare cause of oversensing during implantation procedure of
implantable cardioverter-defibrillator system.
AB - A variety of etiologies can cause erroneous detection in patients with
implantable cardioverter defibrillator (ICDs). Interaction between two
endocardial leads is rare and uncommon in causing electrical noise. During a
reimplantation procedure of an ICD system in a 68-year-old man, additional
electrical signals could be detected. The interaction between two endocardial
defibrillation leads was identified as the cause of sensing problems. When it is
not possible to extract the nonfunctional endocardial lead during implantation of
the new electrode, it should be implanted away and not in parallel from the old
one to avoid interaction between them. A variety of etiologies can cause
erroneous detection in patiens with ICD. Interaction between two endocardial
leads is rare and uncommon to cause electrical noise.
PMID- 17038150
TI - Inadequate ICD discharges due to diaphragmatic electromyopotential oversensing as
the first sign of right ventricular lead perforation.
AB - Right ventricular lead perforation, when acute, is a rare but potentially life
threatening complication of implantable cardioverter defibrillator (ICD) therapy.
We report about a patient with early lead perforation presenting with repetitive
ICD discharges due to oversensing of diaphragmatic electromyopotentials and
describe the management of this complication.
PMID- 17038146
TI - Brugada syndrome.
AB - First introduced as a new clinical entity in 1992, the Brugada syndrome is
associated with a relatively high risk of sudden death in young adults, and
occasionally in children and infants. Recent years have witnessed a striking
proliferation of papers dealing with the clinical and basic aspects of the
disease. Characterized by a coved-type ST-segment elevation in the right
precordial leads of the electrocardiogram (ECG), the Brugada syndrome has a
genetic basis that thus far has been linked only to mutations in SCN5A, the gene
that encodes the alpha-subunit of the sodium channel. The Brugada ECG is often
concealed, but can be unmasked or modulated by a number of drugs and
pathophysiological states including sodium channel blockers, a febrile state,
vagotonic agents, tricyclic antidepressants, as well as cocaine and propranolol
intoxication. Average age at the time of initial diagnosis or sudden death is 40
+/- 22, with the youngest patient diagnosed at 2 days of age and the oldest at 84
years. This review provides an overview of the clinical, genetic, molecular, and
cellular aspects of the Brugada syndrome, incorporating the results of two recent
consensus conferences. Controversies with regard to risk stratification and newly
proposed pharmacologic strategies are discussed.
PMID- 17038151
TI - Isolated giant cell myocarditis in the atrium: an incidental finding?
AB - Giant cell myocarditis (GCM) is an uncommon disorder that affects ventricular
myocardium causing severe left ventricular dysfunction and ventricular
arrhythmias. We report a case of GCM that only affected the atrium sparing the
ventricle.
PMID- 17038152
TI - Atrio-ventricular synchronization by single VDD lead inserted through persistent
left superior vena cava in patient with Turner's syndrome.
AB - A 71-year-old woman with Turner's syndrome underwent pacemaker implantation for
complete atrio-ventricular block. During the procedure, the persistence of left
sided superior vena cava (LSVC) was observed such that the lead, through the
coronary sinus, reached the right atrium. By use of stylets, we could drive the
lead against the lateral atrial wall and curve it through the tricuspid valve
into the right ventricle. The tip reached an apical stable position, obtaining
proper stimulation values. Moreover, the VDD dipole was positioned against high
lateral atrial wall, adequately sensing the atrial potential. So, we could obtain
an atrial synchronous ventricular pacing with only one VDD lead.
PMID- 17038153
TI - Appropriate result from an inappropriate ICD shock.
AB - A case of inappropriate detection of an ungrounded external AC current by an
implantable cardioverter defibrillator (ICD) is reported. The resultant ICD shock
dislodged the patient from the electrical source, thus preventing injury or
electrocution.
PMID- 17038155
TI - "Wide QRS complex tachycardia in a patient with a minute ventilation (MV) rate
responsive pacemaker".
PMID- 17038156
TI - "Viewpoint: fast-track training of non-electrophysiologists to implant
defibrillators: is it needed?".
PMID- 17038157
TI - Handball injuries during major international tournaments.
AB - BACKGROUND: Several authors have analyzed the incidence of handball injuries in
amateur players but information of handball injury in top-level players is very
limited. The aim of the study was to analyze the incidence, circumstances and
characteristics of handball injuries during major international tournaments.
METHODS: Injuries during six international handball tournaments were analyzed,
using an established injury report system. The physicians of all participating
teams were asked to report all injuries after each match on a standardized injury
report form. The response rate was on average 87%. RESULTS: The incidence of
injury was on average 108 injuries/1000 player hours (95% confidence interval
(CI): 98-117) or 1.5 injuries/match (95% CI: 1.4-1.6). The injuries affected most
frequently the lower extremity (42%), followed by injuries of the head (23%),
upper extremity (18%) and trunk (14%). The most frequent diagnosis was contusion
of head (14%) or ankle sprain (8%). The majority of injuries were caused by
contact with another player. The incidence of time loss injuries was on average
27/1000 player hours (95% CI: 22-32), and significantly higher in men than in
women. CONCLUSION: Preventive program proven effective should be implemented.
Fair Play is an essential aspect of injury prevention. Therefore, close
cooperation with the referees is also necessary to make handball a safer sport.
PMID- 17038158
TI - Self-guided brisk walking training with or without poles: a randomized-controlled
trial in middle-aged women.
AB - Walking with poles (Nordic walking, NW) has become popular. We compared training
responses of brisk walking (W) or NW on cardiorespiratory and neuromuscular
fitness. We randomized 121 non-obese sedentary women (aged 50-60) to an NW or W
group (NWG, WG), to train 40 min four times weekly for 13 weeks. Intensity was
based on subjective perception of exertion. Cardiorespiratory performance was
assessed in four levels corresponding to 50%, 65%, 80% and 100% of peak VO(2).
Fifty-four NWG and 53 WG subjects completed the study. The mean intensity was
about 50% of heart rate (HR) reserve. The baseline peak VO(2) was 25.8 (SD 3.9)
mL/min/kg. Both groups improved peak VO(2) similarly (NWG 2.5 mL/min/kg, 95%
confidence interval (CI) 1.9-3.3; WG 2.6, CI 1.9-3.3). In the submaximal stages
while walking with or without poles, HR and lactate decreased after training in
both groups, but the changes were not statistically significantly different
between the groups. Of the neuromuscular tests after training, the only
significant difference between the groups was in the leg strength in the one-leg
squat, favoring WG. In conclusion, both training modes improved similarly health
enhancing physical fitness, and they were feasible and safe.
PMID- 17038159
TI - Strength training effects of whole-body vibration?
AB - Whole-body vibration (WBV) has been suggested to have a beneficial effect on
muscle strength. Manufacturers of vibration platforms promote WBV as an effective
alternative or complement to resistance training. This study aimed to review
systematically the current (August 2005) scientific support for effects of WBV on
muscle strength and jump performance. MEDLINE and SPORT DISCUS were searched for
the word vibration in combination with strength or training. Twelve articles were
included in the final analysis. In four of the five studies that used an adequate
design with a control group performing the same exercises as the WBV group, no
difference in performance improvement was found between groups, suggesting no or
only minor additional effects of WBV as such. Proposed neural mechanisms are
discussed.
PMID- 17038160
TI - Plasma fibrinogen gamma' chain content in the thrombotic microangiopathy
syndrome.
AB - BACKGROUND: Human fibrinogen gamma chain variants, termed gamma' chains, contain
a unique 20-residue sequence after gamma chain residue 407 that ends at
gamma'427, and is designated gamma'(427L). Full-length (FL) gamma'(427L) chains
are constituents of a fibrin-dependent thrombin inhibitory system known as
antithrombin I, whereas a gamma' chain processed in vivo, termed gamma'(423P),
lacks the C-terminal tetrapeptide EDDL, and does not bind thrombin. Together, the
gamma'(423P) and gamma'(427L) chains comprise the total plasma fibrinogen gamma'
chain content. OBJECTIVES: Lowered plasma gamma' chain content (i.e. gamma' chain
containing fibrinogen/total fibrinogen ratio) has been shown to correlate with
susceptibility to venous thrombosis, thus prompting this study on the total and
FL gamma' chain content in 45 subjects with thrombotic microangiopathy (TMA), a
disorder characterized by microvascular thrombosis. METHODS: We measured by
enzyme-linked immunosorbent assay the total gamma' chain-containing
fibrinogen/total fibrinogen (Total gamma'-fgn/Total fgn) ratio and the FL gamma'
chain-containing fibrinogen/total fibrinogen (FL gamma'-fgn/Total fgn) ratio in
these plasmas and in healthy subjects (n = 87). RESULTS: In healthy subjects, the
mean Total gamma'-fgn/Total fgn ratio was 0.127, whereas the FL gamma'-fgn/Total
fgn ratio was somewhat lower at 0.099 (P < 0.0001), a difference reflecting the
presence of gamma'(423P) chains. In TMA plasmas, both the Total gamma'-fgn and FL
gamma'-fgn/Total fgn ratios (0.099 and 0.084, respectively) were lower than those
of their healthy subject counterparts (P < 0.0001). CONCLUSIONS: These findings
in TMA suggest that reductions in the gamma' chain content indicate reduced
antithrombin I activity that may contribute to microvascular thrombosis in TMA.
PMID- 17038161
TI - My life with tissue factor.
PMID- 17038162
TI - Heterologous expression of lcc1 gene from Trametes trogii in Pichia pastoris and
characterization of the recombinant enzyme.
AB - BACKGROUND: Fungal laccases are useful enzymes for industrial applications; they
exhibit broad substrate specificity and thus are able to oxidize a variety of
xenobiotic compounds including chlorinated phenolics, synthetic dyes, pesticides
and polycyclic aromatic hydrocarbons. Unfortunately, the biotechnological
exploitation of laccases can be hampered by the difficulties concerning the
enzyme production by the native hosts. RESULTS: In order to obtain a simple and
efficient source of laccase, the lcc1 cDNA isolated from the white-rot fungus
Trametes trogii has been successfully expressed in the methylotrophic yeast
Pichia pastoris under the control of the methanol induced alcohol oxidase
promoter PAOX1. The recombinant Lcc1 was produced as a secreted protein with the
native N-terminal prepropeptide for signal trafficking, and thus easily recovered
from the culture medium. At the 1-liter scale, as calculated on the basis of the
specific activity, the recombinant protein was produced at a yield of 17 mg/l.
The highest production level obtained in fed-batch culture was 2520 U/l,
corresponding to a specific productivity of 31.5 U/g biomass. The purified
recombinant laccase exhibited a behaviour similar to the main laccase produced by
T. trogii. Lcc1 showed high activity in the presence of organic solvents and a
high decolourization capacity towards azo, triarylmethane, indigo carmine and
anthraquinonic dyes, that could be significantly enhanced in the presence of the
redox mediators 1-hydroxybenzotriazole and violuric acid. CONCLUSION:
Heterologous expression of T. trogii laccase lcc1 in the methylotrophic yeast P.
pastoris was successfully achieved. The biochemical and kinetic characterization
of the recombinant protein suggests potential technological applications for this
enzyme.
PMID- 17038164
TI - Analysis of optimal phenotypic space using elementary modes as applied to
Corynebacterium glutamicum.
AB - BACKGROUND: Quantification of the metabolic network of an organism offers
insights into possible ways of developing mutant strain for better productivity
of an extracellular metabolite. The first step in this quantification is the
enumeration of stoichiometries of all reactions occurring in a metabolic network.
The structural details of the network in combination with experimentally observed
accumulation rates of external metabolites can yield flux distribution at steady
state. One such methodology for quantification is the use of elementary modes,
which are minimal set of enzymes connecting external metabolites. Here, we have
used a linear objective function subject to elementary modes as constraint to
determine the fluxes in the metabolic network of Corynebacterium glutamicum. The
feasible phenotypic space was evaluated at various combinations of oxygen and
ammonia uptake rates. RESULTS: Quantification of the fluxes of the elementary
modes in the metabolism of C. glutamicum was formulated as linear programming.
The analysis demonstrated that the solution was dependent on the criteria of
objective function when less than four accumulation rates of the external
metabolites were considered. The analysis yielded feasible ranges of fluxes of
elementary modes that satisfy the experimental accumulation rates. In C.
glutamicum, the elementary modes relating to biomass synthesis through glycolysis
and TCA cycle were predominantly operational in the initial growth phase. At a
later time, the elementary modes contributing to lysine synthesis became active.
The oxygen and ammonia uptake rates were shown to be bounded in the phenotypic
space due to the stoichiometric constraint of the elementary modes. CONCLUSION:
We have demonstrated the use of elementary modes and the linear programming to
quantify a metabolic network. We have used the methodology to quantify the
network of C. glutamicum, which evaluates the set of operational elementary modes
at different phases of fermentation. The methodology was also used to determine
the feasible solution space for a given set of substrate uptake rates under
specific optimization criteria. Such an approach can be used to determine the
optimality of the accumulation rates of any metabolite in a given network.
PMID- 17038163
TI - Testing statistical significance scores of sequence comparison methods with
structure similarity.
AB - BACKGROUND: In the past years the Smith-Waterman sequence comparison algorithm
has gained popularity due to improved implementations and rapidly increasing
computing power. However, the quality and sensitivity of a database search is not
only determined by the algorithm but also by the statistical significance testing
for an alignment. The e-value is the most commonly used statistical validation
method for sequence database searching. The CluSTr database and the Protein World
database have been created using an alternative statistical significance test: a
Z-score based on Monte-Carlo statistics. Several papers have described the
superiority of the Z-score as compared to the e-value, using simulated data. We
were interested if this could be validated when applied to existing, evolutionary
related protein sequences. RESULTS: All experiments are performed on the ASTRAL
SCOP database. The Smith-Waterman sequence comparison algorithm with both e-value
and Z-score statistics is evaluated, using ROC, CVE and AP measures. The BLAST
and FASTA algorithms are used as reference. We find that two out of three Smith
Waterman implementations with e-value are better at predicting structural
similarities between proteins than the Smith-Waterman implementation with Z
score. SSEARCH especially has very high scores. CONCLUSION: The compute intensive
Z-score does not have a clear advantage over the e-value. The Smith-Waterman
implementations give generally better results than their heuristic counterparts.
We recommend using the SSEARCH algorithm combined with e-values for pairwise
sequence comparisons.
PMID- 17038165
TI - Statistical measures for defining an individual's degree of independence within
state-dependent dynamic games.
AB - BACKGROUND: For organisms living or interacting in groups, the decision-making
processes of an individual may be based upon aspects of both its own state and
the states of other organisms around it. Much research has sought to determine
how group decisions are made, and whether some individuals are more likely to
influence these decisions than others. State-dependent modelling techniques are a
powerful tool for exploring group decision-making processes, but analyses
conducted so far have lacked methods for identifying how dependent an
individual's actions are on the rest of the group. RESULTS: Here, we introduce
and evaluate two easy-to-calculate statistics that quantify how dependent an
individual's actions are upon the state of a co-player in a two-player state
dependent dynamic game. We discuss the merits of these statistics, and situations
in which they would be useful. CONCLUSION: Our statistical measures provide a
means of quantifying how independent an individual's actions are. They also allow
researchers to quantify the output of state-dependent dynamic games, and
quantitatively assess the predictions of these models.
PMID- 17038166
TI - Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with
pneumococcal meningitis: a prospective cohort study.
AB - BACKGROUND: A low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been
identified as an independent risk factor for adverse outcome in adults with
bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with
early meningitis in patients with meningococcal infections, the relation between
CSF WBC and outcome in patients with pneumococcal meningitis is not understood.
METHODS: We examined the relation between CSF WBC, bacteraemia and sepsis in a
prospective cohort study that included 352 episodes of pneumococcal meningitis,
confirmed by CSF culture, occurring in patients aged >16 years. RESULTS: CSF WBC
was recorded in 320 of 352 episodes (91%). Median CSF WBC was 2530 per mm3
(interquartile range 531-6983 per mm3) and 104 patients (33%) had a CSF WBC
<1000/mm3. Patients with a CSF WBC <1000/mm3 were more likely to have an
unfavourable outcome (defined as a Glasgow Outcome Scale score of 1-4) than those
with a higher WBC (74 of 104 [71%] vs. 87 of 216 [43%]; P < 0.001). CSF WBC was
significantly associated with blood WBC (Spearman's test 0.29), CSF protein level
(0.20), thrombocyte count (0.21), erythrocyte sedimentation rate (-0.15), and C
reactive protein levels (-0.18). Patients with a CSF WBC <1000/mm3 more often had
a positive blood culture (72 of 84 [86%] vs. 138 of 196 [70%]; P = 0.01) and more
often developed systemic complications (cardiorespiratory failure, sepsis) than
those with a higher WBC (53 of 104 [51%] vs. 69 of 216 [32%]; P = 0.001). In a
multivariate analysis, advanced age (Odds ratio per 10-year increments 1.22,
95%CI 1.02-1.45), a positive blood culture (Odds ratio 2.46, 95%CI 1.17-5.14),
and a low thrombocyte count on admission (Odds ratio per 100,000/mm3 increments
0.67, 95% CI 0.47-0.97) were associated with a CSF WBC <1000/mm3. CONCLUSION: A
low CSF WBC in adults with pneumococcal meningitis is related to the presence of
signs of sepsis and systemic complications. Invasive pneumococcal infections
should possibly be regarded as a continuum from meningitis to sepsis.
PMID- 17038167
TI - Storage protein profiles in Spanish and runner market type peanuts and potential
markers.
AB - BACKGROUND: Proteomic analysis has proven to be the most powerful method for
describing plant species and lines, and for identification of proteins in complex
mixtures. The strength of this method resides in high resolving power of two
dimensional electrophoresis (2-DE), coupled with highly sensitive mass
spectrometry (MS), and sequence homology search. By using this method, we might
find polymorphic markers to differentiate peanut subspecies. RESULTS: Total
proteins extracted from seeds of 12 different genotypes of cultivated peanut
(Arachis hypogaea L.), comprised of runner market (A. hypogaea ssp. hypogaea) and
Spanish-bunch market type (A. hypogaea ssp. fastigiata), were separated by
electrophoresis on both one- and two-dimensional SDS-PAGE gels. The protein
profiles were similar on one-dimensional gels for all tested peanut genotypes.
However, peanut genotype A13 lacked one major band with a molecular weight of
about 35 kDa. There was one minor band with a molecular weight of 27 kDa that was
present in all runner peanut genotypes and the Spanish-derivatives (GT-YY7, GT
YY20, and GT-YY79). The Spanish-derivatives have a runner-type peanut in their
pedigrees. The 35 kDa protein in A13 and the 27 kDa protein in runner-type peanut
genotypes were confirmed on the 2-D SDS-PAGE gels. Among more than 150 main
protein spots on the 2-D gels, four protein spots that were individually marked
as spots 1-4 showed polymorphic patterns between runner-type and Spanish-bunch
peanuts. Spot 1 (ca. 22.5 kDa, pI 3.9) and spot 2 (ca. 23.5 kDa, pI 5.7) were
observed in all Spanish-bunch genotypes, but were not found in runner types. In
contrast, spot 3 (ca. 23 kDa, pI 6.6) and spot 4 (ca. 22 kDa, pI 6.8) were
present in all runner peanut genotypes but not in Spanish-bunch genotypes. These
four protein spots were sequenced. Based on the internal and N-terminal amino
acid sequences, these proteins are isoforms (iso-Ara h3) of each other, are iso
allergens and may be modified by post-translational cleavage. CONCLUSION: These
results suggest that there may be an association between these polymorphic
storage protein isoforms and peanut subspecies fastigiata (Spanish type) and
hypogaea (runner type). The polymorphic protein peptides distinguished by 2-D
PAGE could be used as markers for identification of runner and Spanish peanuts.
PMID- 17038168
TI - CpGcluster: a distance-based algorithm for CpG-island detection.
AB - BACKGROUND: Despite their involvement in the regulation of gene expression and
their importance as genomic markers for promoter prediction, no objective
standard exists for defining CpG islands (CGIs), since all current approaches
rely on a large parameter space formed by the thresholds of length, CpG fraction
and G+C content. RESULTS: Given the higher frequency of CpG dinucleotides at
CGIs, as compared to bulk DNA, the distance distributions between neighboring
CpGs should differ for bulk and island CpGs. A new algorithm (CpGcluster) is
presented, based on the physical distance between neighboring CpGs on the
chromosome and able to predict directly clusters of CpGs, while not depending on
the subjective criteria mentioned above. By assigning a p-value to each of these
clusters, the most statistically significant ones can be predicted as CGIs.
CpGcluster was benchmarked against five other CGI finders by using a test
sequence set assembled from an experimental CGI library. CpGcluster reached the
highest overall accuracy values, while showing the lowest rate of false-positive
predictions. Since a minimum-length threshold is not required, CpGcluster can
find short but fully functional CGIs usually missed by other algorithms. The CGIs
predicted by CpGcluster present the lowest degree of overlap with Alu
retrotransposons and, simultaneously, the highest overlap with vertebrate
Phylogenetic Conserved Elements (PhastCons). CpGcluster's CGIs overlapping with
the Transcription Start Site (TSS) show the highest statistical significance, as
compared to the islands in other genome locations, thus qualifying CpGcluster as
a valuable tool in discriminating functional CGIs from the remaining islands in
the bulk genome. CONCLUSION: CpGcluster uses only integer arithmetic, thus being
a fast and computationally efficient algorithm able to predict statistically
significant clusters of CpG dinucleotides. Another outstanding feature is that
all predicted CGIs start and end with a CpG dinucleotide, which should be
appropriate for a genomic feature whose functionality is based precisely on CpG
dinucleotides. The only search parameter in CpGcluster is the distance between
two consecutive CpGs, in contrast to previous algorithms. Therefore, none of the
main statistical properties of CpG islands (neither G+C content, CpG fraction nor
length threshold) are needed as search parameters, which may lead to the high
specificity and low overlap with spurious Alu elements observed for CpGcluster
predictions.
PMID- 17038169
TI - Influence of parental employment status on Dutch and Slovak adolescents' health.
AB - BACKGROUND: Recent research shows the possibility that the link between parental
employment status and children's health can be affected by different cultural or
societal settings. The aim of this study was to explore whether the effect of
father's and mother's employment status on several aspects of adolescents' health
differs between Slovakia and the Netherlands. METHODS: Two data sets were used:
2616 Slovak adolescents (mean age 14.9) and 2054 Dutch adolescents (mean age
16.3). Self-rated health, GHQ-12, long-term well-being and Rosenberg self-esteem
scale were used to assess the health of adolescents. Parental employment status
was classified into the following categories: employed, unemployed, disabled,
housewife (among mothers only). Logistic regression analyses were done separately
for males and females. RESULTS: Results indicate that having an unemployed father
negatively influences self-rated health and long-term well-being of Slovak male
adolescents, but has no effect on the health of Dutch adolescents. Secondly,
having a disabled father has a negative effect on the psychological well-being of
Dutch males and the self-rated health of females, but does not influence the
health of Slovak adolescents. Thirdly, having a mother who is disabled,
unemployed or a housewife has a negative effect on the self-esteem of Slovak
adolescents. Fourthly, Dutch males whose mother was a housewife had worse long
term well-being than those with an unemployed mother, whereas Dutch females whose
mother was a housewife reported better psychological well-being than those with
an employed mother. CONCLUSION: To conclude briefly our results, father's
unemployment seems to be a better predictor of health for Slovak adolescents,
father's disablement of health for Dutch ones. Mother's employment status seemed
to be important for the self-esteem of Slovak adolescents and mother as a
housewife for the health of Dutch ones. This suggests that the link between
parental employment status and the health of their children may vary between
countries, and therefore further studies involving various cultures are needed.
PMID- 17038170
TI - African-American mitochondrial DNAs often match mtDNAs found in multiple African
ethnic groups.
AB - BACKGROUND: Mitochondrial DNA (mtDNA) haplotypes have become popular tools for
tracing maternal ancestry, and several companies offer this service to the
general public. Numerous studies have demonstrated that human mtDNA haplotypes
can be used with confidence to identify the continent where the haplotype
originated. Ideally, mtDNA haplotypes could also be used to identify a particular
country or ethnic group from which the maternal ancestor emanated. However, the
geographic distribution of mtDNA haplotypes is greatly influenced by the movement
of both individuals and population groups. Consequently, common mtDNA haplotypes
are shared among multiple ethnic groups. We have studied the distribution of
mtDNA haplotypes among West African ethnic groups to determine how often mtDNA
haplotypes can be used to reconnect Americans of African descent to a country or
ethnic group of a maternal African ancestor. The nucleotide sequence of the mtDNA
hypervariable segment I (HVS-I) usually provides sufficient information to assign
a particular mtDNA to the proper haplogroup, and it contains most of the
variation that is available to distinguish a particular mtDNA haplotype from
closely related haplotypes. In this study, samples of general African-American
and specific Gullah/Geechee HVS-I haplotypes were compared with two databases of
HVS-I haplotypes from sub-Saharan Africa, and the incidence of perfect matches
recorded for each sample. RESULTS: When two independent African-American samples
were analyzed, more than half of the sampled HVS-I mtDNA haplotypes exactly
matched common haplotypes that were shared among multiple African ethnic groups.
Another 40% did not match any sequence in the database, and fewer than 10% were
an exact match to a sequence from a single African ethnic group. Differences in
the regional distribution of haplotypes were observed in the African database,
and the African-American haplotypes were more likely to match haplotypes found in
ethnic groups from West or West Central Africa than those found in eastern or
southern Africa. Fewer than 14% of the African-American mtDNA sequences matched
sequences from only West Africa or only West Central Africa. CONCLUSION: Our
database of sub-Saharan mtDNA sequences includes the most common haplotypes that
are shared among ethnic groups from multiple regions of Africa. These common
haplotypes have been found in half of all sub-Saharan Africans. More than 60% of
the remaining haplotypes differ from the common haplotypes at a single nucleotide
position in the HVS-I region, and they are likely to occur at varying frequencies
within sub-Saharan Africa. However, the finding that 40% of the African-American
mtDNAs analyzed had no match in the database indicates that only a small fraction
of the total number of African haplotypes has been identified. In addition, the
finding that fewer than 10% of African-American mtDNAs matched mtDNA sequences
from a single African region suggests that few African Americans might be able to
trace their mtDNA lineages to a particular region of Africa, and even fewer will
be able to trace their mtDNA to a single ethnic group. However, no firm
conclusions should be made until a much larger database is available. It is
clear, however, that when identical mtDNA haplotypes are shared among many ethnic
groups from different parts of Africa, it is impossible to determine which single
ethnic group was the source of a particular maternal ancestor based on the mtDNA
sequence.
PMID- 17038171
TI - Statistical inference of chromosomal homology based on gene colinearity and
applications to Arabidopsis and rice.
AB - BACKGROUND: The identification of chromosomal homology will shed light on such
mysteries of genome evolution as DNA duplication, rearrangement and loss. Several
approaches have been developed to detect chromosomal homology based on gene
synteny or colinearity. However, the previously reported implementations lack
statistical inferences which are essential to reveal actual homologies. RESULTS:
In this study, we present a statistical approach to detect homologous chromosomal
segments based on gene colinearity. We implement this approach in a software
package ColinearScan to detect putative colinear regions using a dynamic
programming algorithm. Statistical models are proposed to estimate proper
parameter values and evaluate the significance of putative homologous regions.
Statistical inference, high computational efficiency and flexibility of input
data type are three key features of our approach. CONCLUSION: We apply
ColinearScan to the Arabidopsis and rice genomes to detect duplicated regions
within each species and homologous fragments between these two species. We find
many more homologous chromosomal segments in the rice genome than previously
reported. We also find many small colinear segments between rice and Arabidopsis
genomes.
PMID- 17038172
TI - New insight into the role of phosphodiesterase 3A in porcine oocyte maturation.
AB - BACKGROUND: The ovulatory surge of gonadotropins triggers oocyte maturation and
rupture of the ovarian follicle. The resumption of nuclear maturation in the
oocyte from the prophase stage is characterized by germinal vesicle breakdown
(GVBD). It has previously been shown that specific inhibition of cAMP degradation
by PDE3 prevents the resumption of oocyte meiosis. However, no report has
characterized the activity of PDE3 in the porcine oocyte, or the implication of
the cAMP-PDE3 pathway in the entire nuclear maturation process. In this study,
PDE3 activity in the oocyte was assessed during in vitro maturation (IVM) and the
possible roles of the cAMP-PDE3 pathway in the resumption and progression of
meiosis were investigated in terms of different models of oocyte maturation.
RESULTS: Cyclic AMP-degrading PDE activity was detected in the cumulus-oocyte
complex (COC) and was partially inhibited by a specific PDE3 inhibitor,
cilostamide. When measured only in the denuded oocyte, PDE activity was almost
completely inhibited by cilostamide, suggesting that cAMP-PDE3 activity is the
major cAMP-PDE in porcine oocytes. PDE3A mRNA was detected by RT-PCR. PDE3
activity did not vary significantly during the early hours of IVM, but a maximum
was observed at 13 hours. In cumulus-oocyte complexes, meiosis resumed after
20.81 hours of culture. PDE3 inhibition no longer maintained meiotic arrest if
sustained beyond 17.65 hours of IVM, 3 hours prior to resumption of meiosis.
Thereafter, PDE3 inhibition progressively lost its efficacy in GVBD. When the
protein phosphatase 1 and 2A inhibitor okadaic acid was continuously or
transiently (3 hours) present during IVM, meiosis resumed prematurely; PDE3
inhibition was unable to prevent GVBD. However, PDE3 inhibition in COC treated
with OA for 3 hours significantly delayed meiosis at the intermediate stage.
CONCLUSION: The present investigation has demonstrated that PDE3A is the major
cAMP-degrading PDE in the oocyte. It regulates the resumption of meiosis until 3
hours prior to GVBD and transiently affects meiotic progression.
PMID- 17038174
TI - Gene function classification using Bayesian models with hierarchy-based priors.
AB - BACKGROUND: We investigate whether annotation of gene function can be improved
using a classification scheme that is aware that functional classes are organized
in a hierarchy. The classifiers look at phylogenic descriptors, sequence based
attributes, and predicted secondary structure. We discuss three Bayesian models
and compare their performance in terms of predictive accuracy. These models are
the ordinary multinomial logit (MNL) model, a hierarchical model based on a set
of nested MNL models, and an MNL model with a prior that introduces correlations
between the parameters for classes that are nearby in the hierarchy. We also
provide a new scheme for combining different sources of information. We use these
models to predict the functional class of Open Reading Frames (ORFs) from the E.
coli genome. RESULTS: The results from all three models show substantial
improvement over previous methods, which were based on the C5 decision tree
algorithm. The MNL model using a prior based on the hierarchy outperforms both
the non-hierarchical MNL model and the nested MNL model. In contrast to previous
attempts at combining the three sources of information in this dataset, our new
approach to combining data sources produces a higher accuracy rate than applying
our models to each data source alone. CONCLUSION: Together, these results show
that gene function can be predicted with higher accuracy than previously
achieved, using Bayesian models that incorporate suitable prior information.
PMID- 17038175
TI - Differences in polyadenylation site choice between somatic and male germ cells.
AB - BACKGROUND: We have previously noted that there were differences in somatic and
male germ cell polyadenylation site choices. First, male germ cells showed a
lower incidence of the sequence AAUAAA (an important element for somatic
polyadenylation site choice) near the polyadenylation site choice. Second, the
polyadenylation sites chosen in male germ cells tended to be nearer the 5' end of
the mRNA than those chosen in somatic cells. Finally, a number of mRNAs used a
different polyadenylation site in male germ cells than in somatic cells. These
differences suggested that male germ cell-specific polyadenylation sites may be
poor substrates for polyadenylation in somatic cells. We therefore hypothesized
that male germ cell-specific polyadenylation sites would be inefficiently used in
somatic cells. RESULTS: We tested whether pre-mRNA sequences surrounding male
germ cell-specific polyadenylation sites (polyadenylation cassettes) could be
used to direct polyadenylation efficiently in somatic cells. To do this, we
developed a luciferase reporter system in which luciferase activity correlated
with polyadenylation efficiency. We showed that in somatic cells, somatic
polyadenylation cassettes were efficiently polyadenylated, while male germ cell
specific polyadenylation cassettes were not. We also developed a sensitive, 3'
RACE-based assay to analyze polyadenylation site choice. Using this assay, we
demonstrated that male germ cell-specific polyadenylation cassettes were not
polyadenylated at the expected site in somatic cells, but rather at aberrant
sites upstream of the sites used in male germ cells. Finally, mutation of the
male germ cell-specific poly(A) signal to a somatic poly(A) signal resulted in
more efficient polyadenylation in somatic cells. CONCLUSION: These data suggest
that regulated polyadenylation site choice of male germ cell-specific
polyadenylation sites requires one or more factors that are absent from somatic
cells.
PMID- 17038176
TI - Integrative missing value estimation for microarray data.
AB - BACKGROUND: Missing value estimation is an important preprocessing step in
microarray analysis. Although several methods have been developed to solve this
problem, their performance is unsatisfactory for datasets with high rates of
missing data, high measurement noise, or limited numbers of samples. In fact,
more than 80% of the time-series datasets in Stanford Microarray Database contain
less than eight samples. RESULTS: We present the integrative Missing Value
Estimation method (iMISS) by incorporating information from multiple reference
microarray datasets to improve missing value estimation. For each gene with
missing data, we derive a consistent neighbor-gene list by taking reference data
sets into consideration. To determine whether the given reference data sets are
sufficiently informative for integration, we use a submatrix imputation approach.
Our experiments showed that iMISS can significantly and consistently improve the
accuracy of the state-of-the-art Local Least Square (LLS) imputation algorithm by
up to 15% improvement in our benchmark tests. CONCLUSION: We demonstrated that
the order-statistics-based integrative imputation algorithms can achieve
significant improvements over the state-of-the-art missing value estimation
approaches such as LLS and is especially good for imputing microarray datasets
with a limited number of samples, high rates of missing data, or very noisy
measurements. With the rapid accumulation of microarray datasets, the performance
of our approach can be further improved by incorporating larger and more
appropriate reference datasets.
PMID- 17038177
TI - The association between indwelling urinary catheter use in the elderly and
urinary tract infection in acute care.
AB - BACKGROUND: The use of indwelling urinary catheters (IUCs) is thought to be the
most significant risk factor for developing nosocomial urinary tract infections
(UTIs). However, it is unclear how many elderly patients have preexisting
bacteriuria prior to IUC placement. The purpose of this study was to determine 1)
the frequency and appropriateness of IUC use in the Emergency Department (ED) in
elderly patients admitted to our acute care hospital, 2) the percentage of
elderly patients with an IUC who were discharged from the hospital with a
diagnosis of UTI, 3) the percentage of patients with IUCs who were diagnosed and
treated for UTI in the ED or who had admission bacteriuria > or =105 organisms/ml
indicating preexisting UTI, and 4) the percentage of patients with no indication
of UTI on admission who had inappropriately placed IUCs and subsequently were
diagnosed with a UTI. METHODS: Retrospective chart review. Chi square used to
test significance of differences in proportions. RESULTS: Seventy three percent
of patients who received an IUC in the ED were elderly (> or =65 years old).
During the study period, 277 elderly patients received an IUC prior to admission.
Of these, 77 (28%) were diagnosed with UTI during their hospitalization. Fifty
three (69%) of those diagnosed with a UTI by discharge either had the UTI
diagnosed in the ED or had bacteriuria > or =105 organisms/ml prior to IUC
placement. Of the 24 elderly patients who developed a catheter-associated UTI
(i.e., 9% of the elderly population who received an IUC), 11 of the IUCs were
placed inappropriately. Thus, 4% of elderly patients with no indication of UTI on
admission who received an inappropriate IUC in the ED had a primary or secondary
diagnosis of UTI by discharge. The overall rate of nosocomial UTI due to an
inappropriately placed IUC was the same in males and females. CONCLUSION: This
study indicates that the strong association between IUC use and UTI may be partly
explained by the high prevalence of preexisting UTI prior to IUC placement.
Further prospective studies are needed to clarify the true risk vs benefit ratio
for IUC use in acutely ill elderly patients.
PMID- 17038178
TI - Evolution of competence and DNA uptake specificity in the Pasteurellaceae.
AB - BACKGROUND: Many bacteria can take up DNA, but the evolutionary history and
function of natural competence and transformation remain obscure. The sporadic
distribution of competence suggests it is frequently lost and/or gained, but this
has not been examined in an explicitly phylogenetic context. Additional insight
may come from the sequence specificity of uptake by species such as Haemophilus
influenzae, where a 9 bp uptake signal sequence (USS) repeat is both highly
overrepresented in the genome and needed for efficient DNA uptake. We used the
distribution of competence genes and DNA uptake specificity in H. influenzae's
family, the Pasteurellaceae, to examine the ancestry of competence. RESULTS: A
phylogeny of the Pasteurellaceae based on 12 protein coding genes from species
with sequenced genomes shows two strongly supported subclades: the Hin subclade
(H. influenzae, Actinobacillus actinomycetemcomitans, Pasteurella multocida,
Mannheimia succiniciproducens, and H. somnus), and the Apl subclade (A.
pleuropneumoniae, M. haemolytica, and H. ducreyi). All species contained
homologues of all known H. influenzae competence genes, consistent with an
ancestral origin of competence. Competence gene defects were identified in three
species (H. somnus, H. ducreyi and M. haemolytica); each appeared to be of recent
origin. The assumption that USS arise by mutation rather than copying was first
confirmed using alignments of H. influenzae proteins with distant homologues.
Abundant USS-like repeats were found in all eight Pasteurellacean genomes; the
repeat consensuses of species in the Hin subclade were identical to that of H.
influenzae (AAGTGCGGT), whereas members of the Apl subclade shared the consensus
ACAAGCGGT. All species' USSs had the strong consensus and flanking AT-rich
repeats of H. influenzae USSs. DNA uptake and competition experiments
demonstrated that the Apl-type repeat is a true USS distinct from the Hin-type
USS: A. pleuropneumoniae preferentially takes up DNA fragments containing the Apl
type USS over both H. influenzae and unrelated DNAs, and H. influenzae prefers
its own USS over the Apl type. CONCLUSION: Competence and DNA uptake specificity
are ancestral properties of the Pasteurellaceae, with divergent USSs and uptake
specificity distinguishing only the two major subclades. The conservation of most
competence genes over the approximately 350 million year history of the family
suggests that lineages that lose competence may be evolutionary dead ends.
PMID- 17038179
TI - Case report of right hamate hook fracture in a patient with previous fracture
history of left hamate hook: is it hamate bipartite?
AB - BACKGROUND: Hamate hook fracture is a common fracture in golfers and others who
play sports that involve rackets or sticks such as tennis or hockey. This patient
had a previous hamate fracture in the opposing wrist along with potential
features of hamate bipartite. CASE PRESENTATION: A 19 year old male presented
with a complaint of right wrist pain on the ulnar side of the wrist with no
apparent mechanism of injury. The pain came on gradually one week before being
seen in the office and he reported no prior care for the complaint. His history
includes traumatic left hamate hook fracture with surgical excision. CONCLUSION:
The patient was found to have marked tenderness over the hamate and with a prior
fracture to the other wrist, computed tomography of the wrist was ordered
revealing a fracture to the hamate hook in the right wrist. He was referred for
surgical evaluation and the hook of the hamate was excised. Post-surgically, the
patient was able to return to normal activity within eight weeks. This case is
indicative of fracture rather than hamate bipartite. This fracture should be
considered in a case of ulnar sided wrist pain where marked tenderness is noted
over the hamate, especially after participation in club or racket sports.
PMID- 17038180
TI - The Council on Chiropractic Education's new wellness standard: a call to action
for the chiropractic profession.
AB - BACKGROUND: The chiropractic profession has long considered itself to be a
preventive science. Recently the Council on Chiropractic Education (CCE) has
defined a set of standards that must be implemented at all US chiropractic
colleges as of January of 2007. These are specific to wellness measures and
health promoting efforts that should be performed by chiropractors. This will
mandate traditional health promotion and prevention methods be taught to students
at accredited colleges and to practicing chiropractors. OBJECTIVE: To present the
idea of performing traditional health promotion and wellness-concepts in
chiropractic practice as a call to action for clinicians and generate discussion
on the topic. DISCUSSION: This manuscript discusses relevant topics of health
promotion and prevention for chiropractors and other practicing clinicians that
should be made priorities with patients in order to enhance both patient health
and community and population health. CONCLUSION: All practicing chiropractors, as
well as other clinicians should take these new standards from the CCE as a call
to action to begin helping patients address the removable causes of morbidity,
disability and premature mortality where they exist, in addition to treating
their painful spinal conditions.
PMID- 17038181
TI - Genepi: a blackboard framework for genome annotation.
AB - BACKGROUND: Genome annotation can be viewed as an incremental, cooperative, data
driven, knowledge-based process that involves multiple methods to predict gene
locations and structures. This process might have to be executed more than once
and might be subjected to several revisions as the biological (new data) or
methodological (new methods) knowledge evolves. In this context, although a lot
of annotation platforms already exist, there is still a strong need for computer
systems which take in charge, not only the primary annotation, but also the
update and advance of the associated knowledge. In this paper, we propose to
adopt a blackboard architecture for designing such a system RESULTS: We have
implemented a blackboard framework (called Genepi) for developing automatic
annotation systems. The system is not bound to any specific annotation strategy.
Instead, the user will specify a blackboard structure in a configuration file and
the system will instantiate and run this particular annotation strategy. The
characteristics of this framework are presented and discussed. Specific
adaptations to the classical blackboard architecture have been required, such as
the description of the activation patterns of the knowledge sources by using an
extended set of Allen's temporal relations. Although the system is robust enough
to be used on real-size applications, it is of primary use to bioinformatics
researchers who want to experiment with blackboard architectures. CONCLUSION: In
the context of genome annotation, blackboards have several interesting features
related to the way methodological and biological knowledge can be updated. They
can readily handle the cooperative (several methods are implied) and
opportunistic (the flow of execution depends on the state of our knowledge)
aspects of the annotation process.
PMID- 17038182
TI - An educational campaign to increase chiropractic intern advising roles on patient
smoking cessation.
AB - BACKGROUND: Tobacco use, particularly smoking, is the most preventable cause of
death in the United States. More than 400,000 premature deaths are associated
with its use and the health care costs are in the billions. All health care
provider groups should be concerned with patients who continue to smoke and use
tobacco. The US Preventive Services Taskforce and Health People 2010 guidelines
encourage providers to counsel smokers on cessation. Current studies, though
limited regarding chiropractic advising practices indicate a low engagement rate
when it comes to providing cessation information. OBJECTIVE: To test a campaign
regarding initial impact aimed at increasing chiropractic interns advising on
cessation and delivery of information to smokers on cessation. DISCUSSION:
Chiropractic interns do engage patients on smoking status and can be encouraged
to provide more cessation messages and information to patients. The initial
impact assessment of this campaign increased the provision of information to
patients by about 25%. The prevalence of smoking among chiropractic patients,
particularly at teaching clinics may be lower than the national averages.
CONCLUSION: Chiropractic interns can and should be encouraged to advise smokers
about cessation. A systematic method of intake information on smoking status is
needed and a standardized education protocol for chiropractic colleges is needed.
Chiropractic colleges should assess the adequacy of their advising roles and
implement changes to increase cessation messages to their patients as soon as
possible.
PMID- 17038183
TI - Cyclophilin A interacts with diverse lentiviral capsids.
AB - BACKGROUND: The capsid (CA) protein of HIV-1 binds with high affinity to the host
protein cyclophilin A (CypA). This binding positively affects some early stage of
the viral life-cycle because prevention of binding either by drugs that occupy
that active site of cyclophilin A, by mutation in HIV-1 CA, or RNAi that knocks
down intracellular CypA level diminishes viral infectivity. The closely related
lentivirus, SIVcpz also binds CypA, but it was thought that this interaction was
limited to the HIV-1/SIVcpz lineage because other retroviruses failed to interact
with CypA in a yeast two-hybrid assay. RESULTS: We find that diverse
lentiviruses, FIV and SIVagmTAN also bind to CypA. Mutagenesis of FIV CA showed
that an amino acid that is in a homologous position to the proline at amino acid
90 of HIV-1 CA is essential for FIV interactions with CypA. CONCLUSION: These
results demonstrate that CypA binding to lentiviruses is more widespread than
previously thought and suggest that this interaction is evolutionarily important
for lentiviral infection.
PMID- 17038184
TI - Joint distribution approaches to simultaneously quantifying benefit and risk.
AB - BACKGROUND: The benefit-risk ratio has been proposed to measure the tradeoff
between benefits and risks of two therapies for a single binary measure of
efficacy and a single adverse event. The ratio is calculated from the difference
in risk and difference in benefit between therapies. Small sample sizes or
expected differences in benefit or risk can lead to no solution or problematic
solutions for confidence intervals. METHODS: Alternatively, using the joint
distribution of benefit and risk, confidence regions for the differences in risk
and benefit can be constructed in the benefit-risk plane. The information in the
joint distribution can be summarized by choosing regions of interest in this
plane. Using Bayesian methodology provides a very flexible framework for
summarizing information in the joint distribution. RESULTS: Data from a National
Institute of Child Health & Human Development trial of hydrocortisone illustrate
the construction of confidence regions and regions of interest in the benefit
risk plane, where benefit is survival without supplemental oxygen at 36 weeks
postmenstrual age, and risk is gastrointestinal perforation. For the subgroup of
infants exposed to chorioamnionitis the confidence interval based on the benefit
risk ratio is wide (Benefit-risk ratio: 1.52; 90% confidence interval: 0.23 to
5.25). Choosing regions of appreciable risk and acceptable risk in the benefit
risk plane confirms the uncertainty seen in the wide confidence interval for the
benefit-risk ratio--there is a greater than 50% chance of falling into the region
of acceptable risk--while visually allowing the uncertainty in risk and benefit
to be shown separately. Applying Bayesian methodology, an incremental net health
benefit analysis shows there is a 72% chance of having a positive incremental net
benefit if hydrocortisone is used in place of placebo if one is willing to incur
at most one gastrointestinal perforation for each additional infant that survives
without supplemental oxygen. CONCLUSION: If the benefit-risk ratio is presented,
the joint distribution of benefit and risk also should be shown. These regions
avoid the ambiguity associated with collapsing benefit and risk to a single
dimension. Bayesian methods allow even greater flexibility in simultaneously
quantifying benefit and risk.
PMID- 17038185
TI - Integration of curated databases to identify genotype-phenotype associations.
AB - BACKGROUND: The ability to rapidly characterize an unknown microorganism is
critical in both responding to infectious disease and biodefense. To do this, we
need some way of anticipating an organism's phenotype based on the molecules
encoded by its genome. However, the link between molecular composition (i.e.
genotype) and phenotype for microbes is not obvious. While there have been
several studies that address this challenge, none have yet proposed a large-scale
method integrating curated biological information. Here we utilize a systematic
approach to discover genotype-phenotype associations that combines phenotypic
information from a biomedical informatics database, GIDEON, with the molecular
information contained in National Center for Biotechnology Information's Clusters
of Orthologous Groups database (NCBI COGs). RESULTS: Integrating the information
in the two databases, we are able to correlate the presence or absence of a given
protein in a microbe with its phenotype as measured by certain morphological
characteristics or survival in a particular growth media. With a 0.8 correlation
score threshold, 66% of the associations found were confirmed by the literature
and at a 0.9 correlation threshold, 86% were positively verified. CONCLUSION: Our
results suggest possible phenotypic manifestations for proteins biochemically
associated with sugar metabolism and electron transport. Moreover, we believe our
approach can be extended to linking pathogenic phenotypes with functionally
related proteins.
PMID- 17038186
TI - Daily temperature profiles in and around Western Kenyan larval habitats of
Anopheles gambiae as related to egg mortality.
AB - BACKGROUND: Anopheles gambiae eggs are more frequently found on soil around
puddle habitats of the larvae, than on the water surface itself in Western Kenya.
Thus, eggs can experience temperatures more wide-ranging and lethal than those
experienced by larvae or pupae confined within puddles. METHODS: Small batches of
eggs from house-collected An. gambiae as well as from the Kisumu laboratory
strain were bathed for defined times in water whose temperature was precisely
controlled. Daily temperature profiles were recorded by an infrared thermometer
on seven different days in and around three types of typical An. gambiae larval
habitats at Kisian. RESULTS: For wild eggs, significant mortality occurred upon
brief heating between 42-44 degrees C. Few eggs hatched after 10 min at 45
degrees C and none hatched above this temperature. A similar pattern occurred for
eggs of the Kisumu strain, except it was shifted downwards by 1 degrees C. Egg
mortality was time-dependent above 40 degrees C. Temperatures of water in the
three types of larval habitats never exceeded 35 degrees C. Wet or damp mud
rarely and only briefly exceeded 40 degrees C; thus, water and mud would be
highly conducive to egg survival and development. However, dry soils frequently
reached 40-50 degrees C for several h. Eggs stranded on dry surfaces would
experience substantial mortality on hot, sunny days. CONCLUSION: Moist mud around
puddles constitutes suitable habitat for An. gambiae eggs; however, eggs on the
surface of dry soil under direct sunlight are unlikely to survive for more than a
few hours.
PMID- 17038187
TI - Laboratory tests of oviposition by the African malaria mosquito, Anopheles
gambiae, on dark soil as influenced by presence or absence of vegetation.
AB - BACKGROUND: Physical objects like vegetation can influence oviposition by
mosquitoes on soil or water substrates. Anopheles gambiae s. l. is generally
thought to utilize puddles over bare soil as its prime larval habitat and to
avoid standing water populated with vegetation. In Kisian, Kenya near Kisumu,
water often pools in grassy drainage areas both during and after periods of
infrequent rains, when typical puddle habitats become scarce because of drying.
This raised the question of whether An. gambiae has the behavioural flexibility
to switch ovipositional sites when puddles over bare soil are unavailable.
METHODS: To test whether presence and height of grasses influenced oviposition,
wild-caught gravid An. gambiae s. l. were offered paired choices between wet,
bare soil and wet soil populated with mixed grasses or grasses of differing
height. No-choice tests were also conducted by giving females either grassy soil
or bare soil. RESULTS: In choice tests, females laid four times more eggs on
bare, wet soil than soil populated with grasses. However in no-choice tests, egg
output was not significantly different whether grasses were present or not.
Females laid significantly more eggs on soil populated with short grass than with
medium, or tall grass. CONCLUSION: This work shows An. gambiae s. l. has the
capacity to oviposit into grassy aquatic habitats when typical puddles over bare
soil are unavailable. This knowledge will need to be considered in the design and
implementation of programmes aimed at reducing malaria transmission by
suppression of An. gambiae s. l. immatures.
PMID- 17038188
TI - Structural equation and log-linear modeling: a comparison of methods in the
analysis of a study on caregivers' health.
AB - BACKGROUND: In this paper we compare the results in an analysis of determinants
of caregivers' health derived from two approaches, a structural equation model
and a log-linear model, using the same data set. METHODS: The data were collected
from a cross-sectional population-based sample of 468 families in Ontario, Canada
who had a child with cerebral palsy (CP). The self-completed questionnaires and
the home-based interviews used in this study included scales reflecting socio
economic status, child and caregiver characteristics, and the physical and
psychological well-being of the caregivers. Both analytic models were used to
evaluate the relationships between child behaviour, caregiving demands, coping
factors, and the well-being of primary caregivers of children with CP. RESULTS:
The results were compared, together with an assessment of the positive and
negative aspects of each approach, including their practical and conceptual
implications. CONCLUSION: No important differences were found in the substantive
conclusions of the two analyses. The broad confirmation of the Structural
Equation Modeling (SEM) results by the Log-linear Modeling (LLM) provided some
reassurance that the SEM had been adequately specified, and that it broadly
fitted the data.
PMID- 17038190
TI - Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial.
AB - BACKGROUND: Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an
important opportunistic human pathogen. Generally, the acquisition of genes in
the form of pathogenicity islands distinguishes pathogenic isolates from
nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa,
PA14, and compared it with a previously sequenced (and less pathogenic) strain,
PAO1, to identify novel virulence genes. RESULTS: The PA14 and PAO1 genomes are
remarkably similar, although PA14 has a slightly larger genome (6.5 megabses
[Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are
absent in PAO1 to determine which of these genes, if any, contribute to its
enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we
tested 18 additional diverse strains in the C. elegans model and observed a wide
range of pathogenic potential; however, genotyping these strains using a custom
microarray showed that the presence of PA14 genes that are absent in PAO1 did not
correlate with the virulence of these strains. Second, we utilized a full-genome
nonredundant mutant library of PA14 to identify five genes (absent in PAO1)
required for C. elegans killing. Surprisingly, although these five genes are
present in many other P. aeruginosa strains, they do not correlate with virulence
in C. elegans. CONCLUSION: Genes required for pathogenicity in one strain of P.
aeruginosa are neither required for nor predictive of virulence in other strains.
We therefore propose that virulence in this organism is both multifactorial and
combinatorial, the result of a pool of pathogenicity-related genes that interact
in various combinations in different genetic backgrounds.
PMID- 17038189
TI - Comprehensive transcriptional profiling of NaCl-stressed Arabidopsis roots
reveals novel classes of responsive genes.
AB - BACKGROUND: Roots are an attractive system for genomic and post-genomic studies
of NaCl responses, due to their primary importance to agriculture, and because of
their relative structural and biochemical simplicity. Excellent genomic resources
have been established for the study of Arabidopsis roots, however, a
comprehensive microarray analysis of the root transcriptome following NaCl
exposure is required to further understand plant responses to abiotic stress and
facilitate future, systems-based analyses of the underlying regulatory networks.
RESULTS: We used microarrays of 70-mer oligonucleotide probes representing 23,686
Arabidopsis genes to identify root transcripts that changed in relative abundance
following 6 h, 24 h, or 48 h of hydroponic exposure to 150 mM NaCl. Enrichment
analysis identified groups of structurally or functionally related genes whose
members were statistically over-represented among up- or down-regulated
transcripts. Our results are consistent with generally observed stress response
themes, and highlight potentially important roles for underappreciated gene
families, including: several groups of transporters (e.g. MATE, LeOPT1-like);
signalling molecules (e.g. PERK kinases, MLO-like receptors), carbohydrate active
enzymes (e.g. XTH18), transcription factors (e.g. members of ZIM, WRKY, NAC), and
other proteins (e.g. 4CL-like, COMT-like, LOB-Class 1). We verified the NaCl
inducible expression of selected transcription factors and other genes by qRT
PCR. CONCLUSION: Microarray profiling of NaCl-treated Arabidopsis roots revealed
dynamic changes in transcript abundance for at least 20% of the genome, including
hundreds of transcription factors, kinases/phosphatases, hormone-related genes,
and effectors of homeostasis, all of which highlight the complexity of this
stress response. Our identification of these transcriptional responses, and
groups of evolutionarily related genes with either similar or divergent
transcriptional responses to stress, will facilitate mapping of regulatory
networks and extend our ability to improve salt tolerance in plants.
PMID- 17038191
TI - MIMOX: a web tool for phage display based epitope mapping.
AB - BACKGROUND: Phage display is widely used in basic research such as the
exploration of protein-protein interaction sites and networks, and applied
research such as the development of new drugs, vaccines, and diagnostics. It has
also become a promising method for epitope mapping. Research on new algorithms
that assist and automate phage display based epitope mapping has attracted many
groups. Most of the existing tools have not been implemented as an online service
until now however, making it less convenient for the community to access,
utilize, and evaluate them. RESULTS: We present MIMOX, a free web tool that helps
to map the native epitope of an antibody based on one or more user supplied
mimotopes and the antigen structure. MIMOX was coded in Perl using modules from
the Bioperl project. It has two sections. In the first section, MIMOX provides a
simple interface for ClustalW to align a set of mimotopes. It also provides a
simple statistical method to derive the consensus sequence and embeds JalView as
a Java applet to view and manage the alignment. In the second section, MIMOX can
map a single mimotope or a consensus sequence of a set of mimotopes, on to the
corresponding antigen structure and search for all of the clusters of residues
that could represent the native epitope. NACCESS is used to evaluate the surface
accessibility of the candidate clusters; and Jmol is embedded to view them
interactively in their 3D context. Initial case studies show that MIMOX can
reproduce mappings from existing tools such as FINDMAP and 3DEX, as well as
providing novel, rational results. CONCLUSION: A web-based tool called MIMOX has
been developed for phage display based epitope mapping. As a publicly available
online service in this area, it is convenient for the community to access,
utilize, and evaluate, complementing other existing programs. MIMOX is freely
available at http://web.kuicr.kyoto-u.ac.jp/~hjian/mimox.
PMID- 17038192
TI - Application of Poisson kriging to the mapping of cholera and dysentery incidence
in an endemic area of Bangladesh.
AB - BACKGROUND: Disease maps can serve to display incidence rates geographically, to
inform on public health provision about the success or failure of interventions,
and to make hypothesis or to provide evidences concerning disease etiology.
Poisson kriging was recently introduced to filter the noise attached to rates
recorded over sparsely populated administrative units. Its benefit over simple
population-weighted averages and empirical Bayesian smoothers was demonstrated by
simulation studies using county-level cancer mortality rates. This paper presents
the first application of Poisson kriging to the spatial interpolation of local
disease rates, resulting in continuous maps of disease rate estimates and the
associated prediction variance. The methodology is illustrated using cholera and
dysentery data collected in a cholera endemic area (Matlab) of Bangladesh.
RESULTS: The spatial analysis was confined to patrilineally-related clusters of
households, known as baris, located within 9 kilometers from the Matlab hospital
to avoid underestimating the risk of disease incidence, since patients far away
from the medical facilities are less likely to travel. Semivariogram models
reveal a range of autocorrelation of 1.1 km for dysentery and 0.37 km for
cholera. This result translates into a cholera risk map that is patchier than the
dysentery map that shows a large zone of high incidence in the south-central part
of the study area, which is quasi-urban. On both maps, lower risk values are
found in the Northern part of the study area, which is also the most distant from
the Matlab hospital. The weaker spatial continuity of cholera versus dysentery
incidence rates resulted in larger kriging variance across the study area.
CONCLUSION: The approach presented in this paper enables researchers to
incorporate the pattern of spatial dependence of incidence rates into the mapping
of risk values and the quantification of the associated uncertainty. Differences
in spatial patterns, in particular the range of spatial autocorrelation, reflect
differences in the mode of transmission of cholera and dysentery. Our risk maps
for cholera and dysentery incidences should help identifying putative factors of
increased disease incidence, leading to more effective prevention and remedial
actions in endemic areas.
PMID- 17038193
TI - A Fisheye Viewer for microarray-based gene expression data.
AB - BACKGROUND: Microarray has been widely used to measure the relative amounts of
every mRNA transcript from the genome in a single scan. Biologists have been
accustomed to reading their experimental data directly from tables. However,
microarray data are quite large and are stored in a series of files in a machine
readable format, so direct reading of the full data set is not feasible. The
challenge is to design a user interface that allows biologists to usefully view
large tables of raw microarray-based gene expression data. This paper presents
one such interface--an electronic table (E-table) that uses fisheye distortion
technology. RESULTS: The Fisheye Viewer for microarray-based gene expression data
has been successfully developed to view MIAME data stored in the MAGE-ML format.
The viewer can be downloaded from the project web site
http://polaris.imt.uwm.edu:7777/fisheye/. The fisheye viewer was implemented in
Java so that it could run on multiple platforms. We implemented the E-table by
adapting JTable, a default table implementation in the Java Swing user interface
library. Fisheye views use variable magnification to balance magnification for
easy viewing and compression for maximizing the amount of data on the screen.
CONCLUSION: This Fisheye Viewer is a lightweight but useful tool for biologists
to quickly overview the raw microarray-based gene expression data in an E-table.
PMID- 17038194
TI - Global response to pandemic flu: more research needed on a critical front.
AB - If and when sustained human-to-human transmission of H5N1 becomes a reality, the
world will no longer be dealing with sporadic avian flu borne along migratory
flight paths of birds, but aviation flu - winged at subsonic speed along
commercial air conduits to every corner of planet Earth. Given that air
transportation is the one feature that most differentiates present day
transmission scenarios from those in 1918, our present inability to prevent
spread of influenza by international air travel, as reckoned by the World Health
Organization, constitutes a major weakness in the current global preparedness
plan against pandemic flu. Despite the lessons of SARS, it is surprising that
aviation-related health policy options have not been more rigorously evaluated,
or scientific research aimed at strengthening public health measures on the air
transportation front, more energetically pursued.
PMID- 17038195
TI - Expoldb: expression linked polymorphism database with inbuilt tools for analysis
of expression and simple repeats.
AB - BACKGROUND: Quantitative variation in gene expression has been proposed to
underlie phenotypic variation among human individuals. A facilitating step
towards understanding the basis for gene expression variability is associating
genome wide transcription patterns with potential cis modifiers of gene
expression. DESCRIPTION: EXPOLDB, a novel Database, is a new effort addressing
this need by providing information on gene expression levels variability across
individuals, as well as the presence and features of potentially polymorphic
(TG/CA)n repeats. EXPOLDB thus enables associating transcription levels with the
presence and length of (TG/CA)n repeats. One of the unique features of this
database is the display of expression data for 5 pairs of monozygotic twins,
which allows identification of genes whose variability in expression, are
influenced by non-genetic factors including environment. In addition to queries
by gene name, EXPOLDB allows for queries by a pathway name. Users can also upload
their list of HGNC (HUGO (The Human Genome Organisation) Gene Nomenclature
Committee) symbols for interrogating expression patterns. The online application
'SimRep' can be used to find simple repeats in a given nucleotide sequence. To
help illustrate primary applications, case examples of Housekeeping genes and the
RUNX gene family, as well as one example of glycolytic pathway genes are
provided. CONCLUSION: The uniqueness of EXPOLDB is in facilitating the
association of genome wide transcription variations with the presence and type of
polymorphic repeats while offering the feature for identifying genes whose
expression variability are influenced by non genetic factors including
environment. In addition, the database allows comprehensive querying including
functional information on biochemical pathways of the human genes. EXPOLDB can be
accessed at http://expoldb.igib.res.in/expol.
PMID- 17038196
TI - Microbicides 2006 conference.
AB - Current HIV/AIDS statistics show that women account for almost 60% of HIV
infections in Sub-Saharan Africa. HIV prevention tools such as male and female
condoms, abstinence and monogamy are not always feasible options for women due to
various socio-economic and cultural factors. Microbicides are products designed
to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition.
The biannual Microbicides conference took place in Cape Town, South Africa from
23-26 April 2006. The conference was held for the first time on the African
continent, the region worst affected by the HIV/AIDS pandemic. The conference
brought together a record number of 1,300 scientists, researchers, policy makers,
healthcare workers, communities and advocates. The conference provided an
opportunity for an update on microbicide research and development as well as
discussions around key issues such as ethics, acceptability, access and community
involvement. This report discusses the current status of microbicide research and
development, encompassing basic and clinical science, social and behavioural
science, and community mobilisation and advocacy activities.
PMID- 17038197
TI - Development and validation of MIX: comprehensive free software for meta-analysis
of causal research data.
AB - BACKGROUND: Meta-analysis has become a well-known method for synthesis of
quantitative data from previously conducted research in applied health sciences.
So far, meta-analysis has been particularly useful in evaluating and comparing
therapies and in assessing causes of disease. Consequently, the number of
software packages that can perform meta-analysis has increased over the years.
Unfortunately, it can take a substantial amount of time to get acquainted with
some of these programs and most contain little or no interactive educational
material. We set out to create and validate an easy-to-use and comprehensive meta
analysis package that would be simple enough programming-wise to remain available
as a free download. We specifically aimed at students and researchers who are new
to meta-analysis, with important parts of the development oriented towards
creating internal interactive tutoring tools and designing features that would
facilitate usage of the software as a companion to existing books on meta
analysis. RESULTS: We took an unconventional approach and created a program that
uses Excel as a calculation and programming platform. The main programming
language was Visual Basic, as implemented in Visual Basic 6 and Visual Basic for
Applications in Excel 2000 and higher. The development took approximately two
years and resulted in the 'MIX' program, which can be downloaded from the
program's website free of charge. Next, we set out to validate the MIX output
with two major software packages as reference standards, namely STATA (metan,
metabias, and metatrim) and Comprehensive Meta-Analysis Version 2. Eight meta
analyses that had been published in major journals were used as data sources. All
numerical and graphical results from analyses with MIX were identical to their
counterparts in STATA and CMA. The MIX program distinguishes itself from most
other programs by the extensive graphical output, the click-and-go (Excel)
interface, and the educational features. CONCLUSION: The MIX program is a valid
tool for performing meta-analysis and may be particularly useful in educational
environments. It can be downloaded free of charge via http://www.mix-for-meta
analysis.info or http://sourceforge.net/projects/meta-analysis.
PMID- 17038198
TI - TasA-tasB, a new putative toxin-antitoxin (TA) system from Bacillus thuringiensis
pGI1 plasmid is a widely distributed composite mazE-doc TA system.
AB - BACKGROUND: Post-segregational killing systems are present in a large variety of
microorganisms. When found on plasmids, they are described as addiction systems
that act to maintain the plasmid during the partitioning of the cell. The plasmid
to be maintained through the generations harbours a group of two genes, one
coding for a stable toxin and the other coding for an unstable antitoxin that
inhibits the effects of the toxin. If, during cell division, the plasmid is lost,
the toxin and antitoxin proteins present in the cytosol cease to be newly
expressed. The level of unstable antitoxin protein then rapidly decreases,
leaving the toxin free to act on the cellular target, leading to cell death.
Consequently, only cells harbouring the plasmid can survive. RESULTS: The pGI1
plasmid of Bacillus thuringiensis H1.1 harbours a group of two genes, one showing
similarities with the Doc toxin of the phd-doc toxin-antitoxin system,
potentially coding for a toxin-antitoxin system. Attempts were made to clone this
putative system in the Gram-negative host Escherichia coli. The putative
antitoxin tasA was easily cloned in E. coli. However, although several
combinations of DNA fragment were used in the cloning strategy, only clones
containing a mutation in the toxin gene could be recovered, suggesting a toxic
activity of TasB. An exhaustive search was carried out in order to index genes
homologous to those of the putative tasA-tasB system among microorganisms. This
study revealed the presence of this system in great number and in a large variety
of microorganisms, either as tasA-tasB homologues or in association with toxins
(or antitoxins) from other TA systems. CONCLUSION: In this work, we showed that
the pGI1 plasmid of B. thuringiensis H1.1 harbours genes resembling a toxin
antitoxin system, named tasA-tasB for thuringiensis addiction system. This system
appeared to be functional but unregulated in E. coli. Bioinformatics studies
showed that the tasAB system is present on plasmids or chromosomes of a large
variety of microorganisms. Moreover, the association between TasA antitoxin with
toxins other than TasB (and vice versa) revealed the composite and modular nature
of bacterial TA systems.
PMID- 17038199
TI - Diagnostic value and prognostic implications of serum procalcitonin after cardiac
surgery: a systematic review of the literature.
AB - INTRODUCTION: Systemic inflammatory response syndrome is common after surgery,
and it can be difficult to discriminate between infection and inflammation. We
performed a review of the literature with the aims of describing the evolution of
serum procalcitonin (PCT) levels after uncomplicated cardiac surgery,
characterising the role of PCT as a tool in discriminating infection, identifying
the relation between PCT, organ failure, and severity of sepsis syndromes, and
assessing the possible role of PCT in detection of postoperative complications
and mortality. METHODS: We performed a search on MEDLINE using the keyword
'procalcitonin' crossed with 'cardiac surgery,' 'heart,' 'postoperative,' and
'transplantation.' Our search was limited to human studies published between
January 1990 and June 2006. RESULTS: Uncomplicated cardiac surgery induces a
postoperative increase in serum PCT levels. Peak PCT levels are reached within 24
hours postoperatively and return to normal levels within the first week. This
increase seems to be dependent on the surgical procedure and on intraoperative
events. Although PCT values reported in infected patients are generally higher
than in non-infected patients after cardiac surgery, the cutoff point for
discriminating infection ranges from 1 to 5 ng/ml, and the dynamics of PCT levels
over time may be more important than absolute values. PCT is superior to C
reactive protein in discriminating infections in this setting. PCT levels are
higher with increased severity of sepsis and the presence of organ
dysfunction/failure and in patients with a poor outcome or in those who develop
postoperative complications. PCT levels typically remain unchanged after acute
rejection but increase markedly after bacterial and fungal infections. Systemic
infections are associated with greater PCT elevation than is local infection.
Viral infections are difficult to identify based on PCT measurements. CONCLUSION:
The dynamics of PCT levels, rather than absolute values, could be important in
identifying patients with infectious complications after cardiac surgery. PCT is
useful in differentiating acute graft rejection after heart and/or lung
transplantation from bacterial and fungal infections. Further studies are needed
to define cutoff points and to incorporate PCT levels in useful prediction
models.
PMID- 17038200
TI - Psychometric evaluation of a short measure of social capital at work.
AB - BACKGROUND: Prior studies on social capital and health have assessed social
capital in residential neighbourhoods and communities, but the question whether
the concept should also be applicable in workplaces has been raised. The present
study reports on the psychometric properties of an 8-item measure of social
capital at work. METHODS: Data were derived from the Finnish Public Sector Study
(N = 48,592) collected in 2000-2002. Based on face validity, an expert unfamiliar
with the data selected 8 questionnaire items from the available items for a scale
of social capital. Reliability analysis included tests of internal consistency,
item-total correlations, and within-unit (interrater) agreement by rwg index. The
associations with theoretically related and unrelated constructs were examined to
assess convergent and divergent validity (construct validity). Criterion-related
validity was explored with respect to self-rated health using multilevel logistic
regression models. The effects of individual level and work unit level social
capital were modelled on self-rated health. RESULTS: The internal consistency of
the scale was good (Cronbach's alpha = 0.88). The rwg index was 0.88, which
indicates a significant within-unit agreement. The scale was associated with, but
not redundant to, conceptually close constructs such as procedural justice, job
control, and effort-reward imbalance. Its associations with conceptually more
distant concepts, such as trait anxiety and magnitude of change in work, were
weaker. In multilevel models, significantly elevated age adjusted odds ratios
(ORs) of poor self-rated health (OR = 2.42, 95% confidence interval (CI): 2.24
2.61 for the women and OR = 2.99, 95% CI: 2.56-3.50 for the men) were observed
for the employees in the lowest vs. highest quartile of individual level social
capital. In addition, low social capital at the work unit level was associated
with a higher likelihood of poor self-rated health. CONCLUSION: Psychometric
techniques show our 8-item measure of social capital to be a valid tool
reflecting the construct and displaying the postulated links with other
variables.
PMID- 17038201
TI - Development, structure, and function of a novel respiratory organ, the lung-air
sac system of birds: to go where no other vertebrate has gone.
AB - Among the air-breathing vertebrates, the avian respiratory apparatus, the lung
air sac system, is the most structurally complex and functionally efficient.
After intricate morphogenesis, elaborate pulmonary vascular and airway
(bronchial) architectures are formed. The crosscurrent, countercurrent, and
multicapillary serial arterialization systems represent outstanding operational
designs. The arrangement between the conduits of air and blood allows the
respiratory media to be transported optimally in adequate measures and rates and
to be exposed to each other over an extensive respiratory surface while separated
by an extremely thin blood-gas barrier. As a consequence, the diffusing capacity
(conductance) of the avian lung for oxygen is remarkably efficient. The foremost
adaptive refinements are: (1) rigidity of the lung which allows intense
subdivision of the exchange tissue (parenchyma) leading to formation of very
small terminal respiratory units and consequently a vast respiratory surface; (2)
a thin blood-gas barrier enabled by confinement of the pneumocytes (especially
the type II cells) and the connective tissue elements to the atria and
infundibulae, i.e. away from the respiratory surface of the air capillaries; (3)
physical separation (uncoupling) of the lung (the gas exchanger) from the air
sacs (the mechanical ventilators), permitting continuous and unidirectional
ventilation of the lung. Among others, these features have created an incredibly
efficient gas exchanger that supports the highly aerobic lifestyles and great
metabolic capacities characteristic of birds. Interestingly, despite remarkable
morphological heterogeneity in the gas exchangers of extant vertebrates at
maturity, the processes involved in their formation and development are very
similar. Transformation of one lung type to another is clearly conceivable,
especially at lower levels of specialization. The crocodilian (reptilian)
multicameral lung type represents a Bauplan from which the respiratory organs of
nonavian theropod dinosaurs and the lung-air sac system of birds appear to have
evolved. However, many fundamental aspects of the evolution, development, and
even the structure and function of the avian respiratory system still remain
uncertain.
PMID- 17038202
TI - Orchestration of avian reproductive effort: an integration of the ultimate and
proximate bases for flexibility in clutch size, incubation behaviour, and yolk
androgen deposition.
AB - How much effort to expend in any one bout of reproduction is among the most
important decisions made by an individual that breeds more than once. According
to life-history theory, reproduction is costly, and individuals that invest too
much in a given reproductive bout pay with reduced reproductive output in the
future. Likewise, investing too little does not maximize reproductive potential.
Because reproductive effort relative to output can vary with predictable and
unpredictable challenges and opportunities, no single level of reproductive
effort maximizes fitness. This leads to the prediction that individuals
possessing behavioural mechanisms to buffer challenges and take advantage of
opportunities would incur fitness benefits. Here, we review evidence in birds,
primarily of altricial species, for the presence of at least two such mechanisms
and evidence for and against the seasonal coordination of these mechanisms
through seasonal changes in plasma concentrations of the pituitary hormone
prolactin. First, the seasonal decline in clutch size of most bird species may
partially offset a predictable seasonal decline in the reproductive value of
offspring. Second, establishing a developmental sibling-hierarchy among offspring
may hedge against unpredictable changes in resource availability and offspring
viability or quality, and minimize energy expenditure in raising a brood. The
hierarchy may be a product, in part, of the timing of incubation onset relative
to clutch completion and the rate of yolk androgen deposition during the laying
cycle. Because clutch size should influence the effects of both these traits on
the developmental hierarchy, we predicted and describe evidence in some species
that females adjust the timing of incubation onset and rate of yolk androgen
deposition to match clutch size. Studies on domesticated precocial species reveal
an inhibitory effect of the pituitary hormone prolactin on egg laying, suggesting
a possible hormonal basis for the regulation of clutch size. Studies on the
American kestrel (Falco sparverius) and other species suggest that the seasonal
increase in plasma concentrations of prolactin may regulate both a seasonal
advance in the timing of incubation onset and a seasonal increase in the rate of
yolk androgen deposition. These observations, together with strong conceptual
arguments published previously, raise the possibility that a single hormone,
prolactin, functions as the basis of a common mechanism for the seasonal
adjustment of reproductive effort. However, a role for prolactin in regulating
clutch size in any species is not firmly established, and evidence from some
species indicates that clutch size may not be coupled to the timing of incubation
onset and rate of yolk androgen deposition. A dissociation between the regulation
of clutch size and the regulation of incubation onset and yolk androgen
deposition may enable an independent response to the predictable and
unpredictable challenges and opportunities faced during reproduction.
PMID- 17038203
TI - Antimicrobial resistance in non-typhoidal salmonellas from humans in Northern
Ireland, 2001-2003: standardization needed for better epidemiological monitoring.
AB - This study investigated the identification and antimicrobial susceptibility
testing of Salmonella isolates in Northern Ireland during 2001-2003. All six
participating hospital laboratories used similar methods. Identification and
antimicrobial resistance of human enteric (n=897) Salmonella isolates were
analysed by retrospective collation of laboratory records. Resistance of human
Salmonella isolates to nalidixic acid was 16% but resistance to ciprofloxacin or
cefotaxime was rare (<1%). Minor inter-laboratory variations in sensitivity
testing practices make it difficult to compare antimicrobial sensitivity results
reliably and also to monitor for epidemic clones such as S. Typhimurium DT104
with the ACSSuT resistance pattern. The outcome of this study was the adoption of
a standardized regional approach to the isolation of salmonella antimicrobial
resistance. This should improve epidemiological monitoring of epidemic clones and
assure optimum treatment options are available. In cases of treatment failure,
MICs to third-generation cephalosporins and ciprofloxacin should be determined.
PMID- 17038204
TI - Greek measles epidemic strain, 2005-2006.
AB - The purpose of this work was the molecular study of the virus strain that caused
the last measles outbreak in Greece. Twenty-four saliva specimens were obtained
from selected patients serologically confirmed as measles cases between December
2005 and March 2006. Measles virus (MV) detection was performed by a nested RT
PCR. The 447-bp segment of the N gene of these MV strains was used for
genotyping. The N gene sequences of the Greek MV strains were identical to each
other, therefore a phylogenetic tree was constructed using one representative MV
(ThesGRE/06). Our data show that the MV strain which caused the 2005-2006
outbreak in Greece belongs to genotype D6, and differs by 0.68% from the New
Jersey D6 strain and by 5.5% from the MV vaccine strain Edmonston B (U03656)
belonging to genotype A.
PMID- 17038205
TI - Sex differences in brain activation patterns during processing of positively and
negatively valenced emotional words.
AB - BACKGROUND: Previous studies have suggested that men and women process emotional
stimuli differently. In this study, we used event-related functional magnetic
resonance imaging (fMRI) to investigate gender differences in regional cerebral
activity during the perception of positive or negative emotions. METHOD: The
experiment comprised two emotional conditions (positively/negatively valenced
words) during which fMRI data were acquired. RESULTS: Thirty-eight healthy
volunteers (19 males, 19 females) were investigated. A direct comparison of brain
activation between men and women revealed differential activation in the right
putamen, the right superior temporal gyrus, and the left supramarginal gyrus
during processing of positively valenced words versus non-words for women versus
men. By contrast, during processing of negatively valenced words versus non
words, relatively greater activation was seen in the left perirhinal cortex and
hippocampus for women versus men, and in the right supramarginal gyrus for men
versus women. CONCLUSIONS: Our findings suggest gender-related neural responses
to emotional stimuli and could contribute to the understanding of mechanisms
underlying the gender disparity of neuropsychiatric diseases such as mood
disorders.
PMID- 17038206
TI - Ovarian hormones and binge eating in bulimia nervosa.
AB - BACKGROUND: Symptom fluctuation in bulimia nervosa (BN) is related to menstrual
cycle phase. However, the relationship between bulimic symptoms and ovarian
hormones (estrogens and progesterone) has not been examined directly in women
with BN. METHOD: Regularly menstruating women with DSM-IV BN (n=9) and regularly
menstruating controls (n=8) collected hormone samples and recorded mood and
bulimic symptoms daily for 35 consecutive days. Estradiol and progesterone were
measured by radioimmunoassay. Within-subject analyses examined prospective
longitudinal associations between changes in ovarian hormones and changes in
binge frequency in women with BN. Analyses controlled for the possible influence
of negative affect on binge frequency as well as the influence of progesterone
when examining estradiol associations and the influence of estradiol when
examining progesterone associations. Between-subject analyses examined whether
women with BN were more likely to have disrupted hormonal profiles than controls.
RESULTS: Increases in binge eating were significantly associated with both
decreases in estradiol and increases in progesterone in BN women with intact
menstrual cycles. Although BN women were more likely to have disrupted hormone
profiles than controls, this difference did not reach statistical significance,
and mean estradiol and progesterone levels did not differ between bulimic and
control groups. CONCLUSIONS: The results are consistent with those from
experimental animal studies and suggest that decreases in estradiol and increases
in progesterone may contribute to increases in binge eating. Ovarian hormone
function represents a promising candidate for unraveling the neurobiological
mechanisms of binge eating.
PMID- 17038207
TI - DSM-IV alcohol dependence: a categorical or dimensional phenotype?
AB - BACKGROUND: Etiologic research on complex disorders including alcohol dependence
requires informative phenotypes. Information is lost when categorical variables
represent inherently dimensional conditions. We investigated the validity of DSM
IV alcohol dependence as a dimensional phenotype by examining evidence for
linearity and thresholds in associations with validating variables. METHOD:
Current drinkers in the National Longitudinal Alcohol Epidemiologic Survey
(NLAES) (n=18352) and National Epidemiologic Survey of Alcohol and Related
Conditions (NESARC) (n=20836) were analyzed. Validating variables included family
alcoholism, early-onset drinking, and alcohol treatment. Logistic or Poisson
regression modeled the relationships between the validating variables and
dependence in categorical, dimensional or hybrid forms, with severity defined as
number of current DSM-IV alcohol-dependence criteria. Wald tests assessed
differences between models. RESULTS: No evidence was found for boundaries between
categories. Instead, the association of alcohol dependence with the validating
variables generally increased in linear fashion as the number of alcohol
dependence criteria increased. For NLAES models of family alcoholism, early-onset
drinking and treatment, the lines had zero intercepts, with slopes of 0.18, 0.27,
0.70, respectively. For NESARC models of family history and early-onset drinking,
the zero intercept lines had slopes of 0.20, 0.33, and 0.77, respectively. Wald
tests indicated that models representing alcohol dependence as a dimensional
linear predictor best described the association between dependence criteria and
the validating variables. CONCLUSIONS: The sample sizes allowed strong tests.
Diagnoses are necessary for clinical decision-making, but a dimensional alcohol
dependence indicator should provide more information for research purposes.
PMID- 17038208
TI - Lifetime prevalence and inter-cohort variation in DSM-IV disorders in
metropolitan China.
AB - BACKGROUND: This is the first study to examine variation across cohorts in
lifetime risk of DSM-IV mental disorders in metropolitan China. METHOD: Face-to
face household interviews of 2633 adults in Beijing and 2568 adults in Shanghai
were conducted from November 2001 to February 2002 using a multi-stage household
probability sampling method. The Chinese World Mental Health (WMH) Survey
Initiative version of the WHO Composite International Diagnostic Interview (WMH
CIDI) was used for assessment. RESULTS: Lifetime prevalence of any disorder was
13.2%. Alcohol abuse (4.7%), major depressive disorder (3.5%), and specific
phobia (2.6%) were the most common disorders. The median age of onset was later
for mood (43 years) than anxiety (17 years) and substance use (25 years)
disorders. Compared to observed lifetime prevalence, the projected lifetime risk
as of age 75 years increased by 106% for major depressive disorder (7.2%), and
was uniformly higher for all disorders. Relative odds of any lifetime disorder
were 4.7 in the most recent cohorts (ages 18-34) compared to the eldest cohorts
(ages > or =65). CONCLUSIONS: The findings of this cross-sectional study tally
with the view that rapid socioeconomic changes may bring about increasing
incidence of mental disorders in China. However, prospective longitudinal studies
are needed to confirm if the increase is real. Because of the huge size of the
Chinese population, any increase in projected lifetime risk of mental disorders
represents an enormous increase in the number of affected individuals.
PMID- 17038209
TI - Restraint stress influences AP-1 and CREB DNA-binding activity induced by chronic
lithium treatment in the rat frontal cortex and hippocampus.
AB - The therapeutic efficacy of mood stabilizers may involve the regulation of gene
expression mediated by transcription factor activation. In this study, we
investigated AP-1 and cAMP response element-binding protein (CREB) DNA-binding
activity in the rat frontal cortex and hippocampus of rats fed a control diet, a
lithium diet for 7 wk, or 6 wk of lithium, followed by withdrawal for 7 d.
Subsequently, animals were exposed to restraint stress or no stress and the DNA
binding activities assessed at 2, 8 and 24 h post-stress. AP-1 activity was
increased in both brain regions by lithium, an effect that persisted with lithium
discontinuation. Restraint stress induced AP-1 activity in the frontal cortex of
the control group. This stress-induced effect on AP-1 activity was attenuated in
lithium-treated and lithium-withdrawn animals. AP-1 DNA binding was also induced
by stress in the hippocampus of control animals and the activity diminished over
time in the lithium and lithium-withdrawn groups. CREB activity also increased in
the frontal cortex and hippocampus of the lithium-treated group. Stress increased
CREB activity in the frontal cortex of the controls, and was slightly attenuated
with lithium treatment. CREB activity in the hippocampus was insensitive to
stress. The proteins involved in the AP-1 and CREB transcription complexes were
also characterized. Our findings of increased AP-1 and CREB binding after lithium
are consistent with lithium's inhibitory effect on glycogen synthase kinase
3beta, which has been show to negatively regulate AP-1 and CREB transcriptional
activity.
PMID- 17038210
TI - The architecture and function of the light-harvesting apparatus of purple
bacteria: from single molecules to in vivo membranes.
AB - This review describes the structures of the two major integral membrane pigment
complexes, the RC-LH1 'core' and LH2 complexes, which together make up the light
harvesting system present in typical purple photosynthetic bacteria. The antenna
complexes serve to absorb incident solar radiation and to transfer it to the
reaction centres, where it is used to 'power' the photosynthetic redox reaction
and ultimately leads to the synthesis of ATP. Our current understanding of the
biosynthesis and assembly of the LH and RC complexes is described, with special
emphasis on the roles of the newly described bacteriophytochromes. Using both the
structural information and that obtained from a wide variety of biophysical
techniques, the details of each of the different energy-transfer reactions that
occur, between the absorption of a photon and the charge separation in the RC,
are described. Special emphasis is given to show how the use of single-molecule
spectroscopy has provided a more detailed understanding of the molecular
mechanisms involved in the energy-transfer processes. We have tried, with the
help of an Appendix, to make the details of the quantum mechanics that are
required to appreciate these molecular mechanisms, accessible to mathematically
illiterate biologists. The elegance of the purple bacterial light-harvesting
system lies in the way in which it has cleverly exploited quantum mechanics.
PMID- 17038211
TI - Opioid-induced hyperalgesia.
PMID- 17038212
TI - Concentration of levobupivacaine solutions is labelled differently than that of
other local anaesthetic solutions.
PMID- 17038213
TI - Downbeat nystagmus as a manifestation of intrathecal morphine toxicity.
PMID- 17038214
TI - The effect of dexamethasone on recovery from cleft palate surgery.
PMID- 17038215
TI - Severe myalgia associated with propofol sedation.
PMID- 17038216
TI - Paediatric renal transplantation: a single centre study.
PMID- 17038217
TI - Tension pneumocephalus following deep brain stimulation surgery with bispectral
index monitoring.
PMID- 17038218
TI - Ketamine-induced emergence reactions after desflurane anaesthesia.
PMID- 17038219
TI - With bleomycin, that's too much oxygen.
PMID- 17038220
TI - Mitral valve surgery and acute renal failure.
PMID- 17038225
TI - Anaesthetists inability to assess depth of anaesthesia:why not use the IFT?
PMID- 17038226
TI - Value of BIS-monitoring for electroconvulsive therapy.
PMID- 17038227
TI - Sedation in dentistry: current sedation practice in Italy.
PMID- 17038228
TI - Should we aspirate middle-ear effusions prior to insertion of ventilation tubes?
AB - BACKGROUND: Routine aspiration of middle-ear effusions prior to ventilation tube
(grommet) insertion is practised by many surgeons. It has been suggested that
removing the fluid from the middle ear improves immediate post-operative hearing
levels and reduces the chance of the ventilation tube becoming obstructed. The
potential adverse effects of applying suction to the middle ear include acoustic
trauma and an increased risk of tympanosclerosis and otorrhoea. We undertook a
review of the literature in order to determine the benefits or side effects
associated with middle-ear aspiration prior to ventilation tube insertion.
OBJECTIVES: To compare clinical outcomes associated with aspirating versus not
aspirating the middle ear prior to ventilation tube insertion. METHODS: The
Cochrane ENT group trials register, DARE, the Cochrane central register of
controlled trials (CENTRAL), MEDLINE (1960-2005) and EMBASE (1960-2005) were
searched using relevant terms. Reference lists of selected studies were scanned
for additional research material. RESULTS: Seven studies were identified, of
which three fitted the inclusion criteria of our review. Current evidence
suggests that aspiration of middle-ear effusions prior to insertion of
ventilation tubes is not associated with any improvement in clinical outcome, in
terms of post-operative hearing levels, otorrhoea or rates of blockage of
ventilation tubes. Significantly increased rates of tympanosclerosis were
observed in one study and the development of acoustic trauma was observed;
however, no significant association was confirmed. Although more research is
needed, there is no evidence that aspiration of middle-ear effusion prior to
grommet insertion confers any advantage.
PMID- 17038229
TI - Posterior canal wall reconstruction with a composite cartilage titanium mesh
graft in canal wall down tympanoplasty and revision surgery for radical cavities.
AB - OBJECTIVES: To investigate posterior external ear canal wall reconstruction with
a composite cartilage titanium mesh graft in canal wall down tympanoplasty and
revision surgery for open mastoids. STUDY DESIGN: Retrospective case review.
SETTING: Tertiary referral centre. METHODS: As a preliminary study, 15 selected
patients underwent reconstruction of a posterior ear canal wall defect with
titanium mesh. Large defects of the posterior external auditory canal wall,
resulting from canal wall down tympanoplasty or present in revision surgery, were
eliminated by reconstruction using a titanium mesh. The mesh was covered with
conchal cartilage and attached to the cortical mastoid bone using 3-mm titanium
screws. RESULTS: All patients maintained a normal contour of the external ear
canal, without depression, extrusion or infection. There were no failures, based
on short-term post-operative controls. However, two procedures had to be revised
due to incomplete coverage of the titanium mesh. CONCLUSIONS: This study shows
that reconstruction of the posterior ear canal wall with a composite cartilage
titanium mesh is a valuable method for preserving the morphology of the external
auditory canal in selected cases. Problems occurring in canal wall down
tympanomastoidectomy and radical cavities may therefore be avoided. However, long
term results have yet to be evaluated.
PMID- 17038230
TI - Management of clinically diagnosed subacute rhinosinusitis in children under the
age of two years: a randomized, controlled study.
AB - BACKGROUND: In children, a diagnosis of rhinosinusitis is usually made on
clinical grounds. Subacute rhinosinusitis (SRS) may be the cause of persistent
cough, low-grade fever, snoring, ear problems and difficult feeding in children
under the age of two years. OBJECTIVE: To compare the efficacy of culture-based
antibiotics and empiric amoxicillin-clavulanate (40 mg/kg/day) in treating SRS in
children under the age of two years. STUDY DESIGN: Randomized, controlled study.
POPULATION: Sixty children with persistent nasal discharge and nasal obstruction
(and other related symptoms) for 30-90 days. METHODS: Group one (n = 30) received
culture-based antibiotics and group two (n = 30) were treated empirically with 40
mg/kg/day of amoxicillin-clavulanate. Treatment was continued for two weeks.
RESULTS: At the end of the three-week follow-up period, statistically significant
greater improvements in nasal obstruction (p = 0.037) and nasal discharge (p =
0.003) were seen in group one compared with group two. CONCLUSION: culture-based
antibiotics were more efficacious than empiric amoxicillin-clavulanate (40
mg/kg/day) in treating SRS in children under the age of two years.
PMID- 17038231
TI - Validation of sonotubometry in healthy adults.
AB - BACKGROUND: Frequent active opening of the eustachian tube (ET) allows
ventilation of the middle ear and equilibration of pressure changes. Active
opening is accomplished by the contraction of the paratubal muscles during
swallowing. Because a disturbance of the ventilatory function of the ET may
contribute to the development of otitis media with effusion, it is important to
investigate ET function. Sonotubometry can be used to detect whether the ET can
open or not during swallowing acts. METHODS: We developed a sonotubometer to test
ET ventilatory function in 36 healthy adults. The width of the test signal
frequency was between 5500 and 8500 Hz (centre frequency of 7000 Hz) and the
loudness was 95 dB. To test reproducibility, testing took place in two sessions
of 10 swallowing acts each. RESULTS: Opening of the ET could be registered in
91.6 per cent of the subjects in at least one of the two measurements. The first
and the second measurements were highly correlated, with a Spearman's coefficient
of 0.907. CONCLUSION: We confirmed that there is generally a good ventilatory ET
function in otologically healthy adults, although, in a few cases, ET opening was
not registered. Furthermore, we confirmed that our sonometric test equipment had
acceptable reproducibility. Sonotubometry is a promising method for assessing
ventilatory ET function. Research is ongoing to test the discriminative power of
sonotubometry in children with various otological conditions.
PMID- 17038232
TI - Predictive indicators for thyroid cartilage involvement in carcinoma of the
larynx seen on spiral computed tomography scans.
AB - OBJECTIVES: Recent studies have shown that the spiral computed tomography (CT)
scan is a sensitive imaging modality for predicting neoplastic invasion of
thyroid cartilage. The objectives of our study were: to assess the accuracy of
pre-operative spiral CT in predicting thyroid cartilage involvement in patients
with carcinoma of the larynx; and to elucidate the factors that would accurately
indicate cartilage involvement. MATERIAL AND METHODS: Medical records, including
spiral CT scans and pathological reports, were reviewed for 27 patients who had
undergone laryngectomy in two major hospitals in south Wales. A consultant
radiologist with special interest in cross-sectional imaging re-evaluated the
scans to assess neoplastic involvement of the thyroid cartilage, based on
definite, objective criteria. These criteria included: soft tissue asymmetry;
loss of medullary space; spiky or irregular surface; distortion of cartilage
framework; and abnormal soft tissue on both sides of the cartilage. The
radiological findings were then correlated with the histopathological evidence of
cartilage invasion by the tumour. RESULTS: Out of the 27 cases, 15 had evidence
of histological invasion of thyroid cartilage. The most specific criterion to
predict thyroid cartilage involvement was the presence of tumour on both sides of
the cartilage (specificity of 91 per cent, sensitivity of 66 per cent). Combining
two criteria increased both the sensitivity and the specificity to 86 and 91 per
cent, respectively.
PMID- 17038233
TI - Endoscopic pituitary adenomectomy.
AB - The authors' surgical technique for performing pituitary adenomectomy using the
endoscopic transnasal approach is described.
PMID- 17038234
TI - Myxofibrosarcoma of the neck.
AB - We report a rare case of myxofibrosarcoma arising in the neck. A 55-year-old man
presented with a two-year history of left-sided, painless, submandibular
swelling. Computed tomography and magnetic resonance imaging (MRI) revealed an 80
x 35 mm, well defined, lobulated, submandibular tumour extending to the
parapharyngeal space. The tumour showed uniformly low intensity and marked
hyperintensity in T1- and T2-weighted MRI scans, respectively, and was scarcely
enhanced by gadolinium. A tentative diagnosis of lymphangioma or plunging ranula
was made, and the patient underwent local injection of OK-432, which proved to be
ineffective. Resection of the tumour was then performed via a transcervical
approach. The tumour was histopathologically and immunohistochemically diagnosed
as a low-grade myxofibrosarcoma. The patient's post-operative clinical course was
uneventful, and the patient was free of disease 27 months after surgery. The
pathology, clinical characteristics and treatment of myxofibrosarcoma are
bibliographically reviewed.
PMID- 17038235
TI - Coexistent acute pyogenic and tubercular petrous apicitis: a diagnostic dilemma.
AB - We report the case of a 16-year-old boy who presented to us with acute otitis
media, facial weakness and retro-orbital pain. Computed tomography and magnetic
resonance imaging (MRI) scans of the head and temporal bone revealed otitis media
with petrous apicitis. The patient responded to broad-spectrum, parenteral
antibiotics, with disappearance of facial weakness and reduction in pain. One
month following the completion of treatment, the patient continued to have dull
retro-orbital pain and developed ear discharge. A repeat MRI of the temporal bone
revealed a persistent inflammatory lesion in the petrous apex, with a nodular,
ring-enhancing lesion in the cerebellum, strongly suggestive of tuberculosis. The
ear discharge stained positive for acid-fast bacilli and the patient's serum
enzyme-linked immunosorbent assay for tuberculosis was reactive. The patient
responded well to anti-tubercular treatment and was disease free eight months
following the completion of treatment.
PMID- 17038236
TI - Recombinant protein Bd37 protected gerbils against heterologous challenges with
isolates of Babesia divergens polymorphic for the bd37 gene.
AB - The Bd37gene encoding for a glycosyl-phosphatidyl-inositol anchored protein of
Babesia divergens displays genetic polymorphisms among isolates. Five major
polymorphic groups (clades) were shown by PCR-RFLP among different B. divergens
isolates. Each group has been characterized according to a reference Bd37 gene
(Rouen87, W8843, Y5, 6303E and 1705B). Recombinant (GST fusion) protein (Bd37r)
expressed from the Bd37 gene, was used as antigen in a saponin-based formulation
and was able to protect gerbils, after 2 injections at low dose vaccine
concentration (1 mug per dose), against a virulent challenge with the B.
divergens Rouen87 isolate. In spite of polymorphism of Bd37 gene, Bd37r induced
complete immunoprotection against challenges with each of the 5 reference isolate
groups defined by PCR-RFLP.
PMID- 17038237
TI - [Critical illness: nutritional support and treatment].
PMID- 17038238
TI - [Lay emphasis on and advocate strongly nutritional support in clinic].
PMID- 17038239
TI - [From nutritional support to nutritional treatment--a dialectic evolution].
PMID- 17038241
TI - [The indication of parenteral nutrition support (draft)].
PMID- 17038240
TI - [Guidelines of nutritional support in critically ill patients (draft)].
PMID- 17038243
TI - [Influence of glutamine and growth hormone intensified nutrition support on
immunomodulation in critically ill elderly patients].
AB - OBJECTIVE: To evaluate the impacts of glutamine (Gln) and recombinant human
growth hormone (rhGH) intensified nutrition support on critically ill elderly
patients. METHODS: Ninety critically ill aged patients were included in a
prospective, randomized and controlled clinical study, and randomly divided into
three groups: group A (standard nutrition support), group B (standard nutrition
support+10% Gln 100 ml/d), group C (standard nutrition support+ Gln 100 ml/d+rhGH
10 U/d). Before treatment and then 7 and 14 days after treatment, blood samples
were collected for analysis of serum proteins including albumin (ALB), pre
albumin (PAB), C-reactive protein (CRP), immunoglobulin G (IgG). Meanwhile, the
variables including T-cell subsets, CD14 human leukocyte antigen (locus) DR (CD14
HLA-DR), and total lymphocytes were measured. The changes in acute physiology and
chronic health evaluation II (APACHE II) and multiple organ dysfunction syndrome
(MODS) scores, the durations of intensive care unit (ICU) stay and mechanical
ventilation, and 28-day survival rate were recorded. RESULTS: Comparing with
group A and B, the levels of serum ALB, PAB and IgG were significantly elevated
in group C. The T-cell subsets, CD14 HLA-DR and the number of total lymphocytes
were markedly higher in group C (P<0.01), and the APACHE II and MODS scores were
decreased significantly in group C (P<0.05 or P<0.01). The levels of serum CRP
were lowered significantly in group C (P<0.01). There were no significant
differences in the durations of ICU stay, mechanical ventilation and 28-day
survival rate among three groups (all P>0.05). CONCLUSION: Gln and rhGH
intensified nutrition support can improve nutritional condition and immune
function, downregulate the inflammatory response in the critically ill elderly
patients.
PMID- 17038245
TI - [Management of nutritional support and stress hyperglycemia after orthotopic
liver transplantation].
AB - OBJECTIVE: To study the influence of different nutritional regimes on the stress
hyperglycemia and the outcome after orthotopic liver transplantation, for the
purpose of optimizing nutritional regime for early post-operative period.
METHODS: One hundred and seventy-two patients who received liver transplantation
for chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) induced hepatic
function failure or end-stage cirrhosis were enrolled, and the post-operative
complications and length of stay in intensive care unit (ICU) were
retrospectively analyzed, in regard to high caloric (HC) or low caloric (LC)
nutritional regime with their blood glucose controlled to a optimal level.
RESULTS: After the liver transplantation, those patients who were supplied with
LC (83.7-104.6 kJ.kg(-1).d(-1)), energized stepwise with higher fat ratio
(sugar:fat=50%:35%) with blood glucose being maintained <8 mmol/L, had less
exogenous insulin requirement (P<0.01), lower infection-related mortality rate
(P<0.05), and shortened weaning from mechanical ventilation time and length of
stay in ICU (both P<0.05), compared with those who were supplied with HC
nutrition (125.5-146.4 kJ.kg(-1).d(-1)) with routine sugar and fat ratio
(55%:35%), and blood glucose maintained at the same level. However, there was no
significant differences in serum bilirubin contents, incidences of poor healing
of incision and anastomosis as well as hypoglycemia, and extrinsic albumin
requirement between two groups. CONCLUSION: LC nutrition regime and controlling
the blood glucose <8 mmol/L during the early post-operative period may reduce the
incidence of post-operative complications without influencing the prognosis.
PMID- 17038247
TI - [Effect of nutritional support on immunity function in the acquired immune
deficiency syndrome patients].
AB - OBJECTIVE: To investigate the effect of nutritional support on immunity function
in the acquired immune deficiency syndrome (AIDS) patients. METHODS: Sixty-five
AIDS patients were randomly divided into treatment group (n=35) and control group
(n=30). In the treatment group, the patients received enteral nutrition (EN)
treatment or EN supplemented with parenteral nutrition (EN+PN) on top of routine
treatment according to the daily condition of the sufferers. The control group
received routine treatment only. CD3, CD4 and CD8 cell, CD4/CD8, C3, C4,
immunoglobulin G (IgG), IgM, IgA were determined on the 0 and 30th day of the
treatment, and they were analyzed with covariance analysis. RESULTS: CD4 cell in
the treatment group was significantly raised compared with before examination
(P<0.05). Other immunity indexes were not correlated. All clinical indexes showed
no change in the control group (all P>0.05). CONCLUSION: The nutritional support
can raise the immunity function in the AIDS patient.
PMID- 17038248
TI - [Experimental study on gut tolerance to early enteral nutrition following
intestinal ischemia/reperfusion].
AB - OBJECTIVE: To investigate the effects of early enteral nutrition (EEN) on
intestinal function and gut tolerance after intestinal ischemia/reperfusion (I/R)
injury. METHODS: Twenty-four male dogs were randomly divided into three groups:
EEN only, I/R only and I/R+EEN. The superior mesenteric artery (SMA) was blocked
for 1 hour followed by restoration of blood flow. EEN was given 4 hours after
reperfusion by continuous infusion of Fresubin nutrition fluid (4 ml.kg(-1).h(
1), Fresenius Kabi Co, Germany) into gut via a tonometric catheter for 3 hours
till intolerance symptoms, which including vomiting and diarrhea which indicated
gut intolerance. CO(2) partial pressure of intestinal mucosa (PiCO(2)), D-xylose
absorption and intestinal luminal pressure were measured to reflect intestinal
function and perfusion. RESULTS: Incidence and severity of diarrhea and vomiting
were significantly higher in I/R+EEN group (with 87.5% intolerance) than those in
I/R only group (12.5%) and EEN only group (0). After EEN, PiCO(2) and intestinal
cavity pressure were significantly higher, and the D-xylose absorption much
lower, in the I/R+EEN group compared with the I/R group and EEN group (all
P<0.01). CONCLUSION: Intestinal I/R may result in decreased tolerance to EEN. Too
early enteral nutrition (less than 12 hours after gut hypoperfusion) may enhance
intestinal ischemia injury and further inhibit its function of propulsion and
absorption.
PMID- 17038249
TI - [Protective effects of enteral immuno-nutrition on intestinal mucosa injury in
burned rats].
AB - OBJECTIVE: To investigate the protective effects of enteral immuno-nutrition on
intestinal mucosa injury following severe burn. METHODS: Sixty-four Wistar rats
with 30% total body surface area (TBSA) full-thickness burn were randomly divided
into enteral nutrition (EN, n=32) group and enteral immuno-nutrition (EIN, n=32)
group. Another 8 Wistar rats were used as normal control group. The concentration
of secretory immunoglobulin A (sIgA) in intestinal mucosa, the blood levels of
diamine oxidase (DAO) activity and tumor necrosis factor-alpha (TNF-alpha) were
determined, and the expression of TNF-alpha mRNA in intestinal mucosa was
determined by reverse transcription polymerase chain reaction (PT-PCR) in control
group and on 1st, 4th, 7th, and 10th day postburn in EN and EIN group. RESULTS:
Compared with that of before injury, the blood levels of DAO activity, TNF-alpha
content, the concentration of sIgA and the expression of TNF-alpha mRNA in
intestinal mucosa were significantly increased in both EN and EIN groups (P<0.05
or P<0.01). However, the blood levels DAO activity, TNF-alpha content, the
concentration of sIgA on 4th, 7th and 10th postinjury days and the expression of
TNF-alpha mRNA in intestinal mucosa on 1st, 4th, 7th and 10th days postinjury in
EIN group were significantly lower than those in EN group (P<0.05 or P<0.01).
CONCLUSION: EIN can ameliorate the damage of the intestinal mucosa in burned rats
compared with EN group. This might be related to an increase in the sIgA level
and reduction of the expression of TNF-alpha mRNA in intestinal mucosa.
PMID- 17038251
TI - [Comparative study on influence of enteral and parenteral nutrition on organ
function in critically ill patients].
AB - OBJECTIVE: To evaluate the protective effect of enteral nutrition on organ
function in critically ill patients. METHODS: Forty-two critically ill patients
were randomly divided into enteral nutrition group (n=14), total parenteral
nutrition group (n=14), and control group (n=14). The partial pressure of oxygen
in artery (PaO(2)), partial pressure of carbon dioxide in artery (PaCO(2)), white
blood cell count (WBC) and the plasma contents of serum alanine aminotransferase
(ALT), blood urea nitrogen (BUN), and the percentage of gastrointestinal
haemorrhage were determined one week after the nutritional support was initiated.
RESULTS: The WBC, the plasma contents of ALT, and the incidence of
gastrointestinal haemorrhage were significantly higher in control group patients
[(11.70+/-2.85)x10(9)/L, (59.69+/-20.32) U/L, 42.9%] than those in enteral
nutrition group patients [(9.62+/-3.30)x10(9)/L, (40.68+/-22.11) U/L, 21.4%,
P<0.05] and total parenteral nutrition group[(9.82+/-3.50)x10(9)/L, (40.98+/
21.87) U/L, P<0.05, 42.9%], However, PaO(2) in control group patients (62.78+/
4.95) mm Hg was markedly lower than those in enteral nutrition group and
parenteral nutrition group patients [(80.85+/-14.03) mm Hg, (79.88+/-13.73) mm
Hg, both P<0.05]. There was no significant difference in PaCO(2) and the plasma
contents of BUN among the three groups 1 week after treatment were given (all
P>0.05). CONCLUSION: Early stage enteral nutrition could well surpass total
parenteral nutrition. It is conducive to protecting gastrointestinal function,
preventing bacterial translocation, alleviating systemic inflammatory response
and subsequent multiple organ failure among critically ill patients.
PMID- 17038255
TI - [Effects of glutamine given through different avenues on intestine mucosal
barrier function in burned rats].
AB - OBJECTIVE: To observe the effect of glutamine given through different avenues on
intestine mucosal barrier damage induced by severe burn injury. METHODS: One
hundred and sixty Wistar rats were randomly divided into four groups: namely
normal control (C group), burned control (B group), parenteral nutrition with
glutamine (PN+GLN group) and enteral nutrition with glutamine (EN+GLN group).
Rats in B group, PN+GLN group, and EN+GLN group were subjected to 30% total body
surface area (TBSA) full-thickness burn injury. In the latter three groups,
nutritional intake was isonitrogenous and isocaloric. In PN+GLN group and EN+GLN
group the nutrition were supplemented with glutamine 1.0 g.kg(-1).d(-1), and in B
group tyrosine 1.0 g.kg(-1).d(-1). Indexes relevant to injury to the intestine
were determined on postburn day (PBD) 1, 3, 5, 7 and 10. RESULTS: After burn
injury, the index of intestinal mucosal injury, intestine mucosal permeability
and the activity of plasma diamine oxidase (DAO) were significant increased
compared with C group (all P<0.01). On the other hand, the intestine mucosal
blood flow (IMBF), mucosa thickness, villous height, crypt depth and intestinal
epithelial proliferation index were significantly decreased (P<0.05 or P<0.01).
Compared with B group, the extent of changes in these indices were lowered in
PN+GLN group and EN+GLN group (P<0.05 or P<0.01), and the effects were more
marked in EN+GLN group than those in PN+GLN group. CONCLUSION: GLN is beneficial
in minimizing intestinal injury, promoting intestinal mucosal repair. Enteral
supplementation of GLN is a better way of administration.
PMID- 17038253
TI - [Effect of total parenteral nutrition with supplementation of glutamine on the
plasma diamine oxidase activity and D-lactate content in patients with multiple
organ dysfunction syndrome].
AB - OBJECTIVE: To explore the effect of total parenteral nutrition (TPN) supplemented
with glutamine on the activity of plasma diamine oxidase (DAO) and D-lactate
content in blood of patients with multiple organ dysfunction syndrome (MODS).
METHODS: Forty patients with MODS in the intensive care unit (ICU) from September
2003 to June 2005 were involved in a randomized controlled study, and divided
into routine group (group A, n=20), the glutamine +TPN treatment group (group B,
n=20). All patients received equivalent nitrogen and caloric values in parenteral
nutrition. Group A was given routine TPN, and group B was given extra glutamine
0.27 g.kg(-1).d(-1) (i. e. dipeptiven 0.4 g.kg(-1).d(-1)) for 7 days. The
activity of plasma DAO and D-lactate content, the treatment time and the
mortality rate of the two groups were determined before TPN, on the 1st, the 3rd
and the 7th day after TPN. At the same time, 20 healthy blood donors formed the
healthy control group (group C). All the data were analyzed with the SPSS 10.0
software. RESULTS: Before treatment, the activity of plasma DAO and D-lactate
content of the two patient groups were significantly higher than those of group C
(both P<0.01), and there was no difference between group A and group B (P>0.05).
After the treatment of glutamine supplemented TPN, the activity of plasma DAO and
D-lactate content of group B were lower than those of group A (both P<0.01). The
duration of TPN was (15.8+/-2.3) days for group A and (12.5+/-2.4) days for group
B. The former was significantly longer than that of group B (P<0.05). The
mortality rate of group A was 25%, the mortality rate of group B was 10%, but
there was no significant difference between the two groups (P>0.05). CONCLUSION:
The glutamine (dipeptiven) supplementation through vein can help increase the
supply of energy substrate to intestinal mucosa epithelium, and decrease the
activity of plasma DAO and D-lactate content. It has an important effect on
protecting the intestinal mucosa epithelial function. It also helps shorten the
TPN treatment course.
PMID- 17038256
TI - [The time for beginning of enteral nutrition in traumatic shock].
AB - OBJECTIVE: To explore the value of monitoring CO(2) partial pressure of gastric
mucosa (PiCO(2)) in patients with traumatic shock under enteral nutrition (EN)
support. METHODS: Ninety-six patients who were clinically diagnosed as having
traumatic shock were randomly divided into two groups: the test group and the
control group. In the test group, EN was given after tissue oxygenation,
indicated by the value of PiCO(2), approached normal and the clinical symptoms
ameliorated. In control group EN was given at the early stage of recovery from
shock. The course of convalescence of the primary disease, gastro-intestinal
symptoms, the monitoring indexes, and the complications etc. were compared
between the two groups. RESULTS: Acute physiology and chronic health evaluation
II (APACHE II) scores were both gradually lowered in both groups. It was more
significant in the control group than that in the test group 5 days later (both
P<0.01). Compared with the control group, the cure rate in the test group was
increased obviously (91.3% vs. 75.0%, P<0.01), and the hospital stay days were
significantly less [(6.0+/-1.8) days vs. (7.5+/-2.3) days, P<0.01]. CONCLUSION:
It is very important to choose the suitable time to give EN support in patients
with traumatic shock, for it can protect and promote the recovery of the function
of their intestinal tract, raise the survival rate.
PMID- 17038266
TI - Cardiovascular risk factors in adolescents.
AB - Most children who are normal weight for height and otherwise healthy have risk
factor levels associated with the absence of heart disease (ie, they do not
smoke, do not have diabetes, are physically active, have low-density lipoprotein
levels < 110 mg/dL, and have blood pressure < 120/80 mm Hg). However, by
adolescence, the earliest lesions in the atherosclerotic process, fatty streaks
and raised lesions, are present in the coronary arteries and the abdominal aorta.
The severity of early atherogenesis is related to the coexistence of the major
cardiovascular risk factors. Most commonly, the associated risk disturbances are
mild: borderline hypertension, mild dyslipidemia, insulin resistance, overweight,
physical inactivity, and initiation of tobacco use. Rarely, more severe risk
factors are present: familial hypercholesterolemia (a genetic disorder of lipid
metabolism), diabetes mellitus, secondary hypertension of long standing, or risk
factors associated with chronic conditions such as end-stage renal disease. Thus,
cardiovascular risk management in this age group has two components: primordial
prevention (the prevention of the development of cardiovascular risk in the first
place) and primary prevention (more aggressive treatment of identified risk
factors in high-risk individuals either through behavioral or pharmacologic
means). Trials beginning in adolescence of the primary prevention of
atherosclerosis-related diseases have not been undertaken; thus, the decision to
initiate pharmacologic management in high-risk adolescents requires careful
thought.
PMID- 17038267
TI - Smoking, smoking cessation, and risk of cardiovascular disease.
AB - Cigarette smoking increases the risk of atherothrombotic clinical events such as
myocardial infarction and the effect is dose dependent for persons who continue
to smoke. Reductions in smoking habit and smoking cessation are important ways to
improve cardiovascular risk and favorably affect primary and secondary prevention
of clinical disease. Therapeutic methods to improve smoking reduction and
cessation include nicotine replacement, behavioral interventions, and medications
(bupropion, clonidine). Improved cessation rates are under active study and
include behavioral methods, targeting smokers immediately after myocardial
infarction, consideration of depression in smokers, pharmacogenomics to identify
persons who may respond more favorably to specific interventions, and newer
medications that affect endocannabinoid receptors.
PMID- 17038268
TI - LDL-apheresis therapy.
AB - Low-density lipoprotein (LDL)-apheresis is an effective means for acutely
lowering plasma cholesterol (LDL reduction > 60%) and reducing cardiovascular
events in patients with uncontrolled hypercholesterolemia who are genetically
predisposed or resistant to standard therapy. Despite its known benefit,
apheresis is performed in only a minority of qualified patients. In addition to
reducing plasma cholesterol, apheresis can alter other markers of vascular
disease (inflammation, rheology, thrombosis, and fibrinolysis). The acute and
chronic changes to the vascular system may warrant LDL-apheresis use in other
diseases.
PMID- 17038269
TI - Low-density lipoprotein cholesterol lowering in the prevention of CHD: how low
should we go?
AB - The past 12 years have seen the publication of numerous randomized placebo
controlled studies using statins to lower low-density lipoprotein cholesterol
(LDLC) to assess the efficacy of cholesterol lowering on cardiovascular events.
Initial studies predominantly evaluated mortality or nonfatal myocardial
infarctions and coronary heart disease (CHD) death in patients with known or
presumed established coronary disease and moderately elevated to very elevated
serum cholesterol concentrations. Subsequent investigations studied a broader
spectrum of cardiovascular events as a composite primary end point in both
primary and secondary prevention strategies in subjects with lower mean entry
serum LDLC concentrations. These studies have generally shown a reduction in a
composite end point of cardiovascular events, although not necessarily the more
restricted end points used in previous studies. Although the LDLC mantra "lower
is better" has been popularized in advertising and continuing medical education
and suggested as an option in "very high risk" patients by the National
Cholesterol Education Program Adult Treatment Panel, the precise target level for
LDLC for optimal treatment has not been rigorously defined. Serum LDLC less than
100 mg/dL seems reasonable for patients with known atherosclerosis or at high
risk for atherosclerosis (diabetes or presence of multiple risk factors). Serum
LDLC less than 70 mg/dL may be a reasonable goal in the setting of acute coronary
syndromes, but there are many problems with the data on which this recommendation
is made. Furthermore, many advocates of "lower is better" seem oblivious to the
potential downsides of more aggressive lipid-lowering therapy. The LDLC target in
lower risk primary prevention is less clear. What is obvious is that moderate
dose statin therapy can lower CHD risk in primary prevention and secondary
prevention with minimal side effects, and with the imminent availability of
several generic statins, with great cost-effectiveness.
PMID- 17038270
TI - The role of ultrafiltration in the management of heart failure.
AB - In the United States, 90% of one million annual hospitalizations for heart
failure are due to symptoms of volume overload. Hypervolemia contributes to heart
failure progression and mortality. Treatment guidelines recommend that therapy
for patients with heart failure be aimed at achieving euvolemia. Intravenous loop
diuretics induce a rapid diuresis that reduces lung congestion and dyspnea.
However, loop diuretics' effectiveness declines with repeated exposure.
Unresolved congestion may contribute to high re-hospitalization rates.
Furthermore, loop diuretics may be associated with increased morbidity and
mortality due to deleterious effects on neurohormonal activation, electrolyte
balance, and cardiac and renal function. Ultrafiltration is an alternative method
of sodium and water removal, which safely improves hemodynamics in patients with
heart failure. Application of this technology has been limited by the need for
high flow rates, large extracorporeal blood volumes, and large-bore central
venous catheters. A modified ultrafiltration device has overcome these
limitations. Ultrafiltration may be a safe and effective alternative to
intravenous diuretics in the treatment of decompensated heart failure.
PMID- 17038271
TI - The role of exercise therapy in the treatment of patients with systolic heart
failure.
AB - The predominant benefits of exercise training in systolic heart failure have been
seen with aerobic training, although some information exists for the beneficial
effects of resistive training as well. Although men clearly benefit from exercise
training, the effects of exercise in women are less clear. Most of the studies
have used supervised training 3 to 5 days a week for 8 weeks to 6 months, with 30
to 60 minutes of exercise per session. However, home exercise has been reported
in a few studies, and appears to be safe and possibly efficacious. The effects of
training on mortality are unknown at this time, although no study has
demonstrated increased adverse events associated with training. Exercise training
should be recommended for patients with stable New York Heart Association class
II to III heart failure.
PMID- 17038272
TI - The management of atrial fibrillation in heart failure.
AB - The development of atrial fibrillation (AF) can greatly complicate the course of
heart failure (HF). Although recent trials have indicated the nonsuperiority of a
rhythm control strategy in the general population with AF, this may not apply to
patients with HF. We feel strongly that AF be treated aggressively in patients
with HF, defaulting toward an initial rhythm control strategy, to avoid the
hemodynamic detriment of irregular rapid ventricular response and the development
of tachycardia-related myopathy. The index episode is treated with cardioversion
and antiarrhythmic therapy. If significant benefit is demonstrated, the rhythm
control strategy is maintained, to the point of catheter ablation for AF if
necessary. If there is no change in cardiac performance or symptoms after
cardioversion, strict rate control is enforced, to the point of atrioventricular
node ablation and pacing if necessary.
PMID- 17038273
TI - Goals and guidelines for treating hypertension in a patient with heart failure.
AB - Hypertension promotes left ventricular (LV) hypertrophy and myocardial remodeling
and is frequently present in patients with systolic or diastolic heart failure.
Control of hypertension in both of these settings may attenuate progressive LV
hypertrophy and remodeling and improve clinical outcomes. Guidelines for the
management of heart failure recommend that hypertension should be treated in all
patients with preclinical heart failure as well as in those with heart failure
with reduced or preserved LV systolic function. Consistent with national
hypertension guidelines, the goal for blood pressure control in hypertensive
patients with heart failure is less than 140/90 mm Hg, but lower targets (<
130/80 mm Hg) may be desirable in those with concomitant diabetes mellitus or
renal disease. Angiotensin-converting enzyme inhibitors, angiotensin II receptor
antagonists, and beta-adrenoreceptor antagonists are first-line options for
hypertension treatment in heart failure. Calcium channel antagonists and the
alpha blocker doxazosin should be avoided. Episodes of recurrent pulmonary edema
and hypertension may also indicate underlying severe renovascular disease that
may respond to percutaneous renal artery intervention.
PMID- 17038274
TI - Arthrodesis of the subtalar and talonavicular joints for correction of
symptomatic hindfoot malalignment.
AB - BACKGROUND: Triple arthrodesis has long been used for the treatment of painful
malalignment or arthritis of the hindfoot. However, the effect of fusion on
adjacent joints has sparked interest in a more limited arthrodesis in patients
without involvement of the calcaneocuboid joint. METHOD: Results of 16 feet in 14
patients who had a modified double arthrodesis for symptomatic flatfoot,
cavovarus deformity, or hindfoot arthritis were reviewed retrospectively with a
minimum followup of 18 (range 18 to 93) months. The most common diagnosis
contributing to the hindfoot deformity was pes planovalgus. All operations were
done with a consistent technique using rigid internal fixation with screws. In 15
feet, a concomitant gastrocnemius recession for equinus contracture was done at
the time of the primary surgery. Clinical evaluation was based on the American
Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale in addition to
subjective assessments of pain, function, shoewear, cosmesis, and overall
satisfaction. Radiographic evaluation included measurements of the anterior
posterior talo-second metatarsal angle, lateral talocalcaneal angle, and lateral
talo-first metatarsal angle, and notation of arthritic changes of the ankle,
calcaneocuboid, and midfoot joints, as well as an assessment of time to union of
all arthrodeses. RESULTS: The average AOFAS Ankle-Hindfoot Scale improved from
44.7 preoperatively to 77.0 postoperatively (p < 0.01). Subjectively, patients
experienced improvements in pain, function, cosmesis, and shoewear. Overall, all
patients were satisfied and would have the procedure again under similar
circumstances. Radiographically, all parameters statistically improved. There was
an increase in arthritic scores for six ankle, six calcaneocuboid, and five
midfoot joints. One talonavicular joint nonunion occurred in a rheumatoid
patient, requiring revision arthrodesis. CONCLUSIONS: We have concluded that
simultaneous arthrodesis of the talonavicular and subtalar joints is a reasonable
treatment in the subset of patients with symptomatic hindfoot malalignment whose
calcaneocuboid joints are not involved in the primary disease.
PMID- 17038275
TI - Lateral trans-biceps popliteal block for elective foot and ankle surgery
performed after induction of general anesthesia.
AB - BACKGROUND: The purpose of this study was to determine safety and efficacy of
lateral transtendinous popliteal blocks performed after induction of general
anesthesia for intraoperative and postoperative pain control in elective foot and
ankle surgery. METHODS: The charts of 475 consecutive patients were
retrospectively reviewed. The technique was a lateral transtendinous popliteal
block under nerve stimulator direction (described in the text). Patient records
were retrospectively evaluated from the postanesthesia care unit, as well as at
followup on postoperative day 1 and weeks 2, 6, and 12. RESULTS: The block was
complete in 398 patients (83.7%). An incomplete block was found in 77 patients
(16.2 %). In the incomplete category, 21 patients (4.4%) had no pain but some
motor function, 32 patients (6.5%) reported mild to moderate pain, and 24
patients (5.3%) had severe pain. The average block duration was 16.5 hours. There
were no adverse effects documented in any patient at followup. CONCLUSIONS:
Lateral popliteal nerve block after induction of general anesthesia appears to be
safe and effective for intraoperative and postoperative pain control in elective
foot and ankle surgery.
PMID- 17038276
TI - The long-term outcome of tendon lengthening for chronic Achilles tendon pain.
AB - BACKGROUND: The purpose of this study was to assess the long-term results of
tendon lengthening surgery for the treatment of chronic Achilles tendon pain.
METHODS: The results of 21 procedures in 18 patients were assessed. Each patient
had an open Z-plasty to lengthen the Achilles tendon by 1 cm. RESULTS: Results
showed a long-term (7.5 years) reduction in visual analogue pain scores for
sporting activity in 20 of 21 procedures (median 50 point reduction, p < 0.0005).
The tendon lengthening was apparent in a mean increase in dorsiflexion of 5
degrees. Two patients had minor gait abnormalities postoperatively. One patient
had a reduction in plantarflexion power on the operated side, but five patients
had improved power compared to the nonoperated limb. One major and five minor
surgical complications were noted. CONCLUSIONS: The retrospective nature of this
study must be noted in drawing conclusions. However, the results suggest
excellent long-term reduction of Achilles pain after tendon lengthening. This
must be weighed against a relatively high complication rate for any procedure in
this region. This treatment does not appear to cause long-term deficits in
plantarflexion power or gait.
PMID- 17038277
TI - Technique and results of Achilles tendon detachment and reconstruction for
insertional Achilles tendinosis.
AB - BACKGROUND: Insertional Achilles tendinosis is a clinical entity that commonly
occurs with other posterior heel disorders such as retrocalcaneal bursitis,
Haglund deformity, intratendinous ossification and pretendinous bursitis.
Complete detachment and reconstruction of the Achilles tendon was evaluated as a
method of treatment for this condition. METHODS: Seventy-five patients (81 heels)
were treated over a 5-year period for chronic insertional Achilles tendinosis.
These were divided in two groups: a nondetached group (26 patients, 31 heels,
average age 55 years) included all patients with debridement of the Achilles
tendon with no or partial detachment of the tendon, and a detached group (49
patients, 50 heels, average age 56.1 years) that included all patients with
complete detachment, debridement, and reattachment with suture anchors of the
Achilles tendon associated with proximal V-Y lengthening of the proximal
aponeurosis. Sixty-one patients (65 heels) were contacted for an interview
questionnaire, 22 patients from the nondetached group (26 heels) and 39 patients
from the detached group (39 heels). The average followup for the nondetached
group was 47 months and for the detached group 33 months. Items evaluated
included pain, activity limitation, gait change, walking distance, return to
sport or work, and level of satisfaction. RESULTS: No statistically significant
differences were noted in relation to any of the items evaluated. In the
nondetached group, the satisfaction rate was 92%, and 8% were dissatisfied. In
the detached group, 74% were completely satisfied and 18% were satisfied with
reservations. Eight percent were dissatisfied. Complications included minor wound
dehiscence (one in the nondetached, five in the detached group), wound infection
(one in the nondetached group, two in the detached group) and sural neuritis (two
in the detached group). CONCLUSIONS: Complete detachment of the Achilles tendon
and reattachment with suture anchors and a proximal V-Y lengthening was a
reliable and effective method of treatment for severe chronic insertional
Achilles tendinosis as was debridement of the tendon insertion without detachment
for less severe involvement.
PMID- 17038278
TI - The use of standing lateral tibial-calcaneal angle as a quantitative measurement
of Achilles tendon contracture in adult acquired flatfoot.
AB - BACKGROUND: To quantitate the association of Achilles tendon contracture (ATC)
with adult acquired flatfoot, the authors hypothesized that the standing lateral
tibial-calcaneal angle increases because of ATC. METHODS: The standing lateral
tibial-calcaneal angle, talo-first metatarsal angle, lateral talocalcaneal angle,
lateral standing medial cuneiform, arch height, and anteroposterior talonavicular
coverage angle were measured in 21 patients (25 feet) with clinical diagnoses of
ATC and adult acquired flatfoot (AAF) and compared to the same measurements in a
control group of 15 patients (30 feet) with no foot deformities or previous foot
surgeries. RESULTS: The mean lateral tibial-calcaneal angle in the control group
was 64.43 degrees and in the AAF group 71.24 degrees (p < 0.001). The mean
lateral talo-first metatarsal angle in the control group was 11.77 degrees, and
in the AAF group with ATC it was 25.80 degrees (p < 0.001). The mean arch height
in the control group was 17.90 mm and in the AAF group, 8.48 mm (p < 0.001). In
the ATC and AAF group an increasing standing lateral tibial-calcaneal angle was
correlated with a decreasing lateral talo-calcaneal angle (p = 0.044), and a
decreasing arch height was correlated to an increasing lateral talo-first
metatarsal angle (p < 0.001). CONCLUSION: Adults with flatfeet and Achilles
tendon contracture may have a statistically significant increase in the standing
lateral tibial-calcaneal angle. This angle may be a reproducible measure of ATC.
An increase in the standing lateral tibial-calcaneal angle may confirm and
quantitate the clinical diagnosis of Achilles tendon contracture. Further studies
with more patients are needed.
PMID- 17038279
TI - Flexor hallucis longus tendon transfer for hallux claw toe deformity and vertical
instability of the metatarsophalangeal joint.
AB - BACKGROUND: Historically, operative treatment of hallux claw toe deformity has
been the Jones procedure or one of its modifications. Review of the literature
confirms its ability to maintain alignment and achieve patient satisfaction;
however, several complications have been reported. Many of these are related to
altered biomechanics across the metatarsophalangeal (MTP) joint. A similar
approach to this clinical problem involves restoration of the flexion moment
across the MTP joint without an interphalangeal (IP) joint arthrodesis. METHODS:
We conducted a retrospective review of 10 patients who had a flexor hallucis
longus (FHL) tendon transfer to the proximal phalanx of the great toe for hallux
claw toe deformity, as well as for symptomatic vertical instability. Four
patients had a positive drawer test indicating vertical instability without
static deformity. Two patients with vertical instability were found to have a
dynamic deformity. Mean followup was 24 (SD 15.2) months. RESULTS: All
deformities were corrected and alignment was maintained at the time of followup.
Pain under the first metatarsal head was reliably improved in symptomatic
patients (p < 0.05). Patient satisfaction also was assessed. All six patients
treated for hallux claw deformity were satisfied with their outcomes. Two of the
four patients treated for vertical instability were satisfied. The other two
patients expressed dissatisfaction because of persistent pain that occurred
during strenuous exercise. Their symptoms during routine activity were improved,
however. CONCLUSION: Based on initial results, the FHL transfer to the proximal
phalanx appears to be a viable treatment option for hallux claw deformity in
terms of deformity correction, pain relief, and patient satisfaction. Further
evaluation is warranted regarding the indication of vertical instability.
PMID- 17038280
TI - Thromboembolic disease after foot and ankle surgery.
AB - BACKGROUND: The incidence and potential life-threatening complications of
thromboembolic disease after major orthopaedic surgery has been extensively
studied. However, there are two studies pertaining to the incidence of
thromboembolic disease after foot and ankle surgery, the findings of which
suggest that the incidence is too low to justify routine thromboprophylaxis.
METHODS: This is a retrospective study identifying the incidence of
thromboembolic disease after foot and ankle surgery in the practices of two foot
and ankle specialists. The purpose of the study was to evaluate the risk factors
for the development of thromboembolic disease and to examine the issue of routine
thromboprophylaxis. Six hundred and two patients were included in this study.
RESULTS: There was a 4% incidence (24 patients) of postoperative thromboembolic
complications. Risk factors identified for postoperative thromboembolic disease
were a history of rheumatoid arthritis, a recent history of air travel, previous
deep vein thrombosis or pulmonary embolism, and limb immobilization. CONCLUSIONS:
The incidence of thromboembolic disease after foot and ankle surgery could be
higher than that previously reported particularly if a patient has certain risk
factors. Prospective randomized clinical trials are needed to establish the true
incidence of thromboembolic disease after foot and ankle surgery and to define
the indications for routine thromboprophylaxis.
PMID- 17038281
TI - Diagnosis and treatment of malignant melanoma of the foot.
AB - BACKGROUND: Patients diagnosed with melanoma of the foot have been reported to
have a poor prognosis. We reviewed our experience at a tertiary-care medical
clinic to determine the disease course in patients diagnosed with melanoma of the
foot. METHODS: A retrospective review was performed of 38 patients with a
diagnosis of primary or locally recurrent melanoma of the foot treated between
January, 1988, and July, 2004. The main outcome measures included methods of
diagnosis, clinical and histopathologic features, and patterns of recurrence.
RESULTS: The mean age at diagnosis was 61 years; most were women (58%) and
Caucasian (95%). The average time to diagnosis was 17 months. Initial clinical
diagnosis had been considered benign in 12 (32%). The median Breslow thickness
was 1.75 mm, T1 lesions were the most common, and acral lentiginous melanoma
accounted for 42%. Thirteen patients (34%) had ulcerated lesions. Sentinel lymph
node biopsy specimens of 25 patients identified four (16%) with metastatic
disease. Surgical complications occurred in 12 patients, usually after skin graft
or soft-tissue flap reconstruction. Systemic recurrence developed in six
patients, four of whom also had regional recurrence. CONCLUSIONS: Most patients
were elderly Caucasian women and most presented with early-stage disease, but
diagnosis can be difficult and a subgroup presented with thick melanomas.
Reconstructive surgical procedures had a high rate of complications; however,
overall functional outcomes were good. Stage of cancer at diagnosis was
associated with systemic metastases.
PMID- 17038282
TI - A cotton batting compression dressing and fiberglass cast used safely in the
immediate postoperative period after hindfoot or ankle surgery.
AB - BACKGROUND: Patients undergoing surgery on the foot and ankle who require
immobilization are typically placed in splints or soft compression dressings
after surgery to avoid complications associated with swelling. As swelling
subsides, this temporary immobilization is removed and replaced with a short-leg
cast, making an additional office visit necessary, which adds to the cost as well
as patient discomfort. METHODS: We apply a cast in the operating room using a
special padding technique to accommodate postoperative swelling. It is supportive
enough that it does not need to be replaced shortly after surgery. This cast was
applied to 38 patients having surgery on the hindfoot or ankle between March,
2003, and February, 2004. RESULTS: All patients tolerated the cast during the
initial 2 weeks after surgery, and there were no complications. CONCLUSION: The
purpose of this study was to describe the casting technique and document its
safety for use immediately after surgery on the hindfoot and ankle.
PMID- 17038283
TI - Midline posterior approach to the ankle and hindfoot.
AB - BACKGROUND: The posterior approach to the ankle and hindfoot can be used for
fixation of fractures, fusions, or osteotomies and is especially useful in
patients with poor soft tissue anteriorly, medially, or laterally. However, a
high rate of wound complications has been reported with standard posterolateral
and posteromedial approaches. Because of local wound problems with the standard
approaches, we have used a midline posterior approach and a longitudinal midline
splitting of the Achilles tendon. This approach provides excellent exposure while
minimizing wound healing complications. This approach provides dissection between
angiosomes, which should optimize preservation of the blood supply to the skin
flaps. METHODS: We retrospectively evaluated wound healing in 33 consecutive
patients who had surgery using the modified midline posterior approach. The mean
age of the patients was 48 (range 16 to 83) years. The mean followup was 24
(range 12 to 73) months. Surgical procedures included ankle and pantalar
arthrodeses (primary and revision), talectomies with tibiocalcaneal arthrodesis,
repairs of fracture nonunions, reconstruction of a chronic Achilles rupture, and
hardware removal with multiple debridements of chronic osteomyelitis. RESULTS:
There were no instances of skin flap necrosis. One patient with diabetic
neuropathic arthropathy developed a small superficial wound eschar that healed
with dressing changes alone. Four patients developed deep infections; two of
these had a history of deep infection and the other two had significant
comorbidities. CONCLUSIONS: The modified midline posterior approach to the distal
tibia, ankle, and hindfoot has a low primary wound complication rate without
sacrificing exposure. This approach can be used for any procedure requiring
posterior access to the distal tibia, ankle joint, or subtalar joint.
PMID- 17038284
TI - Instant 99mTc-ciprofloxacin scintigraphy for the diagnosis of osteomyelitis in
the diabetic foot.
AB - BACKGROUND: The diagnosis of osteomyelitis of the foot in patients with diabetes
mellitus remains a challenge. This study was conducted to evaluate bone
infections using scintigraphy with instantly prepared single-vial kit, radio
labeled ciprofloxacin (Diagnobact TM) in comparison to a bacterial culture taken
from the involved site. METHODS: Twenty-five patients with type 2 diabetes
mellitus having foot ulcers, including six with superficial ulcers and positive
99mTc-methylene diphosphonate (MDP) bone scan as a control, were subjected to
99mTc-ciprofloxacin scan and subsequent bacteriological culture. RESULTS: 99mTc
ciprofloxacin scan was positive in 13 patients and negative in 12 patients,
including the six with superficial ulcers. Bacterial culture was positive in 18
patients and negative in seven, including one with osteomyelitis on bone biopsy
only. 99mTc-ciprofloxacin scan showed "true positive" results in 12, "true
negative" in six, "false positive" in one, and "false negative" in six. The
specificity and sensitivity of the test were 66.7% and 85.7%, respectively. The
positive and negative predictive values and an accuracy of 92.8%, 50% and 72%,
respectively. Staphylococcus aureus and Escherichia coli were the most frequently
isolated organisms. CONCLUSION: 99mTc-ciprofloxacin is a sensitive and specific
marker to diagnose bone infection in patients with diabetes mellitus, but care
must be taken in case of fastidious organisms and ciprofloxacin-resistant
bacterial flora in which false results may be obtained.
PMID- 17038285
TI - Gliding resistance of the posterior tibial tendon.
AB - BACKGROUND: Abnormal gliding of the posterior tibial tendon may lead to
mechanical trauma, degeneration, and eventually posterior tibial tendon
dysfunction. Our study analyzed the gliding resistance of the posterior tibial
tendon in intact feet and in feet with simulated flatfoot deformity. METHODS: An
experimental system was developed that allowed direct measurement of gliding
resistance at the tendon-sheath interface. Seven normal fresh-frozen cadaver foot
specimens were studied, and gliding resistance between the posterior tibial
tendon and sheath was measured. The effects of ankle and hindfoot position and
the effect of flatfoot deformity on gliding resistance were analyzed. Gliding
resistance was measured for 4.9 N applied load to the tendon. RESULTS: Mean
gliding resistance for the neutral position was 77 +/- 13.1 (x10(-2) N). Compared
to neutral position, dorsiflexion increased gliding resistance and averaged 130
+/- 38.9 (x10(-2) N), and plantarflexion decreased gliding resistance and
averaged 35 +/- 12.6 (x10(-2) N). Flatfoot deformity increased gliding resistance
compared to normal feet, averaging 104 +/- 17.0 (x10(-2) N) for neutral, 205 +/-
55.0 (x10(-2) N) for dorsiflexion, and 58 +/- 21.3 (x10(-2) N) for
plantarflexion. CONCLUSIONS: The findings indicate that patients with a
preexisting flatfoot deformity may be predisposed to develop posterior tibial
tendon dysfunction because of increased gliding resistance and trauma to the
tendon surface.
PMID- 17038286
TI - Using resident input to identify and integrate essential components of a foot and
ankle rotation.
AB - BACKGROUND: Foot and ankle surgery is one of the orthopaedic subspecialties to
which residents not uncommonly receive limited exposure. Therefore, it is
important to identify what both faculty and residents regard as fundamental to a
foot and ankle rotation. The purposes of this study were to identify the
essential components of a foot and ankle rotation and to correlate these with the
American Orthopaedic Foot and Society (AOFAS) core curriculum, and to discuss how
to integrate resident input and AOFAS guidelines into a valued foot and ankle
rotation. METHODS: Over a 5-year period, each orthopaedic resident beginning a 10
week postgraduate year (PGY) 3 foot and ankle rotation was asked to choose topics
to be covered during weekly 45-minute discussion conferences. Each resident also
identified personal goals for the rotation. Data were collected in this
prospective nature, and the responses of the 24 PGY 3 residents from our program
who completed the rotation between February, 2000, and April, 2005, were
analyzed. The discussion conference topics were compared to the AOFAS guidelines,
and the top 10 personal goals were determined. Prerotation and postrotation
Orthopaedic Inservice Training Examination (OITE) foot and ankle scores for the
residents also were analyzed. RESULTS: Among the nine AOFAS core curriculum
categories, residents most frequently chose chronic soft-tissue foot and ankle
problems, followed in frequency by foot and ankle arthritis, foot and ankle
trauma, and diabetic foot. Individually, posterior tibial tendon insufficiency,
hallux valgus, diabetic foot, and calcaneal fracture were the most frequently
chosen discussion conference topics. In regards to personal goals for the
rotation, residents most commonly wanted to improve their physical examination
skills (88%) and increase their orthotic knowledge (71%). The OITE scores
improved by a mean of 12% after the rotation. CONCLUSIONS: This study provides
new and detailed information about resident expectations for a valued foot and
ankle rotation. These results should be integrated with existing AOFAS guidelines
to further refine the essential components of a core foot and ankle curriculum.
PMID- 17038287
TI - Crank-shaped arthrodesis for a flatfoot with a bipartite navicular: a case
report.
PMID- 17038288
TI - Internal rotation of the proximal fibular fragment producing symptomatic
tibiofibular impingement after an SER-II ankle fracture: a case report.
PMID- 17038289
TI - Plantar fracture-dislocation of the intermediate cuneiform: case report.
PMID- 17038290
TI - Clinical tip: Late medial ankle pain as indicator of syndesmotic instability.
PMID- 17038291
TI - Correction of severe valgus deformity during ankle arthrodesis: technique tip.
PMID- 17038292
TI - Current concepts review: Stress fractures of the foot.
PMID- 17038293
TI - Carotid artery stenting with distal protection using the carotid wallstent and
filterwire neuroprotection: single-center experience of 380 cases with midterm
outcomes.
AB - Emerging data have supported the clinical efficacy of carotid artery stenting
(CAS) in stroke prevention in high-risk surgical patients. This study was
performed to evaluate the midterm clinical outcome of CAS using the Carotid
Wallstent and FilterWire distal protection (both Boston Scientific, Natick, MA)
at an academic institution. Risk factors for in-stent restenosis (ISR) were also
analyzed. Clinical variables and treatment outcome of high-risk patients who
underwent Carotid Wallstent placement with FilterWire EX/EZ neuroprotection were
analyzed during a recent 54-month period. Three hundred eighty CAS procedures
were performed in 354 patients. Technical success was achieved in 372 cases
(98%), and symptomatic lesions existed in 85 (24%) patients. No patient
experienced periprocedural mortality or neuroprotective device-related
complication. The 30-day stroke and death rate was 2.7%, and the overall
complication rate was 6.9%. The overall major or fatal stroke rates in
symptomatic and asymptomatic patients were 4.6% and 1.3%, respectively (not
significant). The overall stroke and death rates between the symptomatic and
asymptomatic groups were 5.8% and 2.4%, respectively (not significant). The
median follow-up period was 29 months (range 1-53 months). With Kaplan-Meier
analysis, the rates of freedom from 60% or greater ISR after CAS procedures at
12, 24, 36, and 48 months were 97%, 94%, 92%, and 90%, respectively. The rates of
freedom from all fatal and nonfatal strokes at 12, 24, 36, and 48 months were
97%, 91%, 89%, and 85%, respectively. Multivariable analysis of significant
univariate predictors identified that postendarterectomy stenosis (odds ratio
[OR] 3.98, p = .02) and multiple stent placement (OR 3.68, p = .03) were
independent predictors of ISR. Our study yielded favorable short-term and midterm
clinical results using Carotid Wallstent with FilterWire neuroprotection. Late
follow-up results showed low rates of fatal and nonfatal stroke and favorable ISR
rates compared with other carotid stent trials. Postendarterectomy and multiple
stent placement were associated with subsequent ISR.
PMID- 17038294
TI - Transcervical carotid stenting with flow reversal for neuroprotection: technique,
results, advantages, and limitations.
AB - Carotid angioplasty and stenting are progressively earning a role as a less
invasive alternative in the treatment of carotid occlusive disease. The most
common approach for carotid artery stenting involves transfemoral access and use
of a filter or balloon device for neuroprotection. This approach has limitations
related to both the site of access and the method of neuroprotection.
Specifically, an aortoiliac segment with advanced occlusive or aneurysmal disease
or an anatomically unfavorable or atheromatous arch and arch branches can
significantly limit the safety of the retrograde transfemoral pathway to the
carotid bifurcation. Additionally, data provided by the use of transcranial
Doppler monitoring and diffusion-weighted magnetic resonance imaging in patients
undergoing filter- or balloon-protected carotid artery stenting demonstrate that
currently available devices are associated with a considerable incidence of
cerebral embolization. To address these limitations, we, along with others, have
employed a direct transcervical approach for carotid artery stenting that
incorporates the principle of flow reversal for neuroprotection. The technique
bypasses all of the anatomic limitations of transfemoral access and simplifies
the application of flow reversal, which is one of the safest neuroprotection
techniques. The purpose of this review is to describe our method of transcervical
carotid artery stenting, review the accumulating outcomes data, and discuss the
clinical advantages of and indications for this increasingly popular technique.
PMID- 17038295
TI - Training in carotid artery stenting: do carotid simulation systems really help?
AB - Virtual reality (VR) simulations have long been used for training in aviation and
other professions. High-fidelity endovascular procedure simulators are now
available, providing procedure simulations with real-time interactions; two
dimensional graphic displays of angiographic anatomy; mechanical interfaces with
guidewires, sheaths, and catheters that provide some degree of haptic feedback;
modeling of physiologic and pharmacology responses; and other features.
Simulators have been incorporated into training programs for physicians learning
carotid artery stenting (CAS). For the first time, US Food and Drug
Administration approval of a new device (CAS systems) has included a requirement
for physician training that incorporates the use of VR simulators. Early
experience has shown that simulation is well accepted by trainees, performance on
simulators improves with training and practice, and simulation prior to first
performing endovascular procedures can improve clinical performance. Specific to
CAS, the value of education programs using simulators appears to be tangible as
trained but inexperienced CAS operators have clinical results comparable to those
of physicians with extensive CAS experience.
PMID- 17038296
TI - Aneurysm sac pressure measurement with a pressure sensor in endovascular aortic
aneurysm repair.
AB - Aortic endograft surveillance is a necessity for the lifetime of a patient owing
to the risk of endoleaks and device complications. The current standard of care
for surveillance is radiologic imaging. The most commonly used modality is
computed tomographic angiography. Magnetic resonance angiography and
ultrasonography have also been used as surveillance tools. These imaging
techniques have risks and limitations, and alternative surveillance tools are
being investigated. Remote pressure sensing is a promising technology that can
provide adjunctive support to the current imaging modalities. The technology is
applicable to both abdominal and thoracic endograft implantation and
surveillance. It has recently gained clearance from the US Food and Drug
Administration for acute aneurysm exclusion during an abdominal endograft
insertion. As more data are accumulated, it may be possible for remote pressure
sensing to replace current imaging techniques as the sole modality for endograft
surveillance.
PMID- 17038297
TI - Percutaneous thoracic and abdominal aortic aneurysm repair: techniques and
outcomes.
AB - Endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) has become a
widely accepted treatment modality. The conventional approach of an EVAR involves
bilateral groin incisions to expose the femoral arteries followed by introducer
sheath placement, which is typically performed with the use of general or
epidural anesthesia. As technology trends toward less invasive methods and sheath
sizes become smaller, the use of a total percutaneous approach to endovascular
repair of aortic pathology is becoming more common. In this review, we present a
brief history of percutaneous closure devices for common femoral artery access,
factors important in patient selection, the technique of performing a
percutaneous EVAR procedure, early and late complications, and overall outcomes
of percutaneous approaches for the endovascular treatment of aortic pathology.
PMID- 17038298
TI - Management of aortic aneurysms and dissections with the Zenith TX2 stent graft.
AB - Endovascular repair of thoracic aortic aneurysms offers a less invasive
alternative to conventional surgery, similar to its counterpart in the abdominal
aorta. Although its long-term durability and outcome remain relatively unknown,
published midterm results from clinical trials suggest comparable rates of
aneurysm-related mortality and significant reductions in early morbidity compared
with open repair. The Zenith TX2 stent graft (Cook Endovascular, Bloomington, IN)
is an investigational endovascular device that is designed to treat aneurysms and
other degenerative pathologies of the thoracic aorta. At the time of this
writing, it is nearing completion of its pivotal trial. Clinical experience with
this device is limited to countries outside the United States and to sites
participating in the clinical trials. The purpose of this article is to provide a
description of the Zenith TX2 device and its application in the repair of
thoracic aortic aneurysms and dissections.
PMID- 17038299
TI - Indications and results with cryoplasty in the treatment of infrainguinal
arterial occlusive disease.
AB - Percutaneous transluminal angioplasty of the superficial femoral and popliteal
arteries has been an accepted therapy for short focal stenosis. Elastic recoil
and flow-limiting dissection have limited the durability of angioplasty,
especially in long lesions and total occlusions. Cryoplasty couples cold therapy
with angioplasty to induce mechanical and biologic effects to reduce elastic
recoil and potentially to reduce restenosis. The mechanical and biologic
mechanisms of this therapy are discussed. The results of cryoplasty for
femoropopliteal lesions from a single-center series and a multicenter registry
are reviewed. Cryoplasty appears to improve patency over conventional angioplasty
and to reduce the need for bailout stenting in femoropopliteal stenoses and
occlusions < 10 cm in length. Cryoplasty appears to be promising to treat
critical limb ischemia in patients with tibial disease.
PMID- 17038300
TI - Endovascular treatment of popliteal artery aneurysms.
AB - Popliteal artery aneurysms are relatively uncommon but potentially limb
threatening lesions that can thrombose or cause distal embolization.
Identification of these aneurysms, especially in patients with abdominal aortic
aneurysms, is imperative, and prophylactic treatment with either surgical
exclusion and bypass or endoluminal stent grafting is critical to prevent these
poor outcomes. Endovascular approaches currently using the Viabahn stent graft
offer several advantages, including a minimally invasive approach, fewer
perioperative complications, and a faster recovery. This must be balanced with a
potentially higher failure rate or requirement for reintervention, although
contemporary series report comparable short-term outcomes. We present our
approach to the evaluation and diagnosis of popliteal aneurysms, the technical
aspects of endovascular popliteal aneurysm repair, and a representative case
study.
PMID- 17038301
TI - Utility of retrievable vena cava filters and mechanical thrombectomy in the
endovascular management of acute deep venous thrombosis.
AB - Endovascular interventions of symptomatic deep venous thrombosis (DVT) using
various therapeutic modalities, such as thrombolysis, mechanical thrombectomy,
and inferior vena cava (IVC) filter placement, have received increased focus
owing in part to advances in catheter-based interventional technologies. Although
systemic anticoagulation remains the primary treatment modality in DVT, catheter
based interventions can provide rapid removal of large thrombus burden and
possibly preserve venous valvular function in patients with symptomatic DVT. This
article reviews current endovascular treatment strategies for acute DVT.
Specifically, the utility of mechanical thrombectomy along with various temporary
IVC filters in the setting of DVT is examined. Lastly, an illustrative case of
acute DVT that was treated with endovascular intervention with IVC filter
placement is presented.
PMID- 17038302
TI - Infrainguinal arterial intervention: is there a role for an atherectomy device?
AB - Excision of atheromatous plaque is an attractive option for the minimally
invasive treatment of peripheral arterial disease. Approved for use in 2003, the
SilverHawk Plaque Exicison System (FoxHollow Technologies, Redwood City, CA) is a
catheter-based plaque excision device allowing percutaneous removal of
atheromatous material. This device represents the most recent generation of
atherectomy tools. Overall experience with plaque debulking in the peripheral
arteries spans almost two decades, and understanding of the technique continues
to evolve. This article reviews the technology, current practices, and data on
plaque excision.
PMID- 17038305
TI - Citalopram and suicidality in adult major depression and anxiety disorders.
AB - The suicide-related data on citalopram from controlled clinical trials in
depression and anxiety disorders were analysed. Safety data from placebo
controlled and relapse prevention citalopram trials in depression/major
depressive disorder (MDD) and anxiety were searched for specific events relating
to fatal suicide, non-fatal self-harm or suicidal thoughts. Efficacy data (item
10, suicidal thoughts, on the Montgomery-Asberg Depression Rating Scale [MADRS])
were also analysed. In the clinical trial database, the number of adverse events
(fatal suicide, non-fatal self-harm or suicidal thoughts) was low, both during
the first 2 weeks of treatment and during the full treatment period, with no
statistically significant differences between citalopram and placebo. There was
one fatal suicide during treatment (after 12 weeks of double-blind treatment in a
relapse-prevention trial) for a patient treated with citalopram (incidence: 0.4%;
rate: 0.010) and none on placebo. Citalopram was significantly more efficacious
than placebo in lowering suicidal thoughts, based on efficacy rating (MADRS, item
10). There was no indication from this review of clinical trial data that
citalopram may increase the risk of suicide in patients with MDD or anxiety.
However, the patients in these clinical trials represent a selected group, as
those patients with a significant risk of suicide were excluded at trial onset.
PMID- 17038304
TI - Biotin uptake by rabbit corneal epithelial cells: role of sodium-dependent
multivitamin transporter (SMVT).
AB - PURPOSE: The objective of this research was to investigate the presence of sodium
dependent multivitamin transporter (SMVT) on rabbit corneal epithelial cells.
METHODS: Primary cultured rabbit corneal epithelial cells (rPCECs)and freshly
excised rabbit corneas were used for characterization of biotin uptake and
transport, respectively. Reverse transcription-polymerase chain reaction (RT-PCR)
was performed to confirm the molecular identity of SMVT. Liquid
chromatography/tandem mass spectrometry (LC-MS/MS) analysis was performed to
examine the presence of biotin in rabbit tears. RESULTS: Uptake of biotin by
rPCECs was found to be time and concentration dependent with Km of 32.52 microM
and Vmax of 10.43 pmol min- 1 mg protein- 1. Biotin was significantly inhibited
in the presence of pantothenic acid and lipoic acid. Biotin uptake was found to
be energy and Na+ dependent but H+ and Cl- independent. The uptake was inhibited
by valeric acid in a concentration-dependent manner but not much affected in the
presence of biotin methyl ester and biocytin with no free carboxyl group.
Modulators of both PKC- and PKA-mediated pathways had no effect on biotin uptake,
but calcium-calmodulin inhibitor significantly inhibited its uptake. Sodium
dependent multivitamin transporter was identified by RT-PCR in rPCECs. Transport
experiments across the rabbit corneas revealed the functional localization of
SMVT on the apical side of the cornea, and thereby corroborating with in vitro
results with cultured corneal cells. Finally, LC-MS/MS analysis showed the
presence of biotin in rabbit tears. CONCLUSIONS: Results obtained from both in
vitro and exvivo studies suggest the possible role of SMVT expressed on corneal
epithelial cells for the uptake of biotin, which co-transports pantothenic acid
and lipoic acid. Further, the presence of biotin in tears suggests the
physiological significance of this transporter in rabbit corneal epithelium.
PMID- 17038306
TI - Image-guided system with miniature robot for precise positioning and targeting in
keyhole neurosurgery.
AB - This paper describes a novel image-guided system for precise automatic targeting
in minimally invasive keyhole neurosurgery. The system consists of the MARS
miniature robot fitted with a mechanical guide for needle, probe or catheter
insertion. Intraoperatively, the robot is directly affixed to a head clamp or to
the patient's skull. It automatically positions itself with respect to predefined
targets in a preoperative CT/MRI image following an anatomical registration with
an intraoperative 3D surface scan of the patient's facial features and
registration jig. We present the system architecture, surgical protocol, custom
hardware (targeting and registration jig), and software modules (preoperative
planning, intraoperative execution, 3D surface scan processing, and three-way
registration). We also describe a prototype implementation of the system and in
vitro registration experiments. Our results indicate a system-wide target
registration error of 1.7 mm (standard deviation = 0.7 mm), which is close to the
required 1.0-1.5 mm clinical accuracy in many keyhole neurosurgical procedures.
PMID- 17038307
TI - Synergistic effects of the SAPK/JNK and the proteasome pathway on glial
fibrillary acidic protein (GFAP) accumulation in Alexander disease.
AB - Protein aggregates in astrocytes that contain glial fibrillary acidic protein
(GFAP), small heat shock proteins, and ubiquitinated proteins are termed
Rosenthal fibers and characterize Alexander disease, a leukodystrophy caused by
heterozygous mutations in GFAP. The mechanisms responsible for the massive
accumulation of GFAP in Alexander disease remain unclear. In this study, we show
that overexpression of both wild type and R239C mutant human GFAP led to
cytoplasmic inclusions. GFAP accumulation also led to a decrease of proteasome
activity and an activation of the MLK2-JNK pathway. In turn, the expression of
activated mixed lineage kinases (MLKs) induced JNK activation and increased GFAP
accumulation, whereas blocking the JNK pathway decreased GFAP accumulation.
Activated MLK also inhibited proteasome function. A direct inhibition of
proteasome function pharmacologically further activated JNK. Our data suggest a
synergistic interplay between the proteasome and the SAPK/JNK pathway in the
context of GFAP accumulation. Feedback interactions among GFAP accumulation,
SAPK/JNK activation, and proteasomal hypofunction cooperate to produce further
protein accumulation and cellular stress responses.
PMID- 17038308
TI - Heparan sulfate analysis from diabetic rat glomeruli.
AB - One of the major complicating factors in insulin-dependent diabetes mellitus is
nephropathy. Several investigators have linked heparan sulfate (HS) alterations
in the glomerular basement membrane (GBM) with albuminuria as a marker of
abnormal blood filtration and the subsequent progression to renal failure. In
this study, we examined the fine structure of HS in the glomerulus and the GBM
isolated from the kidneys of rats injected with streptozotocin. Using fluorophore
assisted carbohydrate electrophoresis, we obtained disaccharide composition
analyses for HS. In a time course study, we observed that normal rat HS isolated
from the GBM becomes more N-sulfated as the glomeruli mature over a period of 8
weeks. Diabetic rats injected with streptozotocin at the beginning of this period
showed a reversal of this trend. Using a graded sieve technique, we found that
two different sizes of glomeruli could be isolated from the rat kidneys and that
there was a significant difference in the HS disaccharide content between these
two pools of glomeruli. Only the larger sized glomeruli had less N-sulfation of
HS as a result of insulin-dependent diabetes mellitus. This change in the fine
structure of HS was localized to the GBM and was not associated with cell surface
HS. We also generated oligosaccharides of HS that portray fine structural
alterations in the diabetic rats indicative of a loss of the sulfation of N
acetylglucosamine.
PMID- 17038309
TI - Evolutionary and functional conservation of the DNA non-homologous end-joining
protein, XLF/Cernunnos.
AB - Non-homologous end-joining is a major pathway of DNA double-strand break repair
in mammalian cells, deficiency in which confers radiosensitivity and immune
deficiency at the whole organism level. A core protein complex comprising the
Ku70/80 heterodimer together with a complex between DNA ligase IV and XRCC4 is
conserved throughout eukaryotes and assembles at double-strand breaks to mediate
ligation of broken DNA ends. In Saccharomyces cerevisiae an additional NHEJ
protein, Nej1p, physically interacts with the ligase IV complex and is required
in vivo for ligation of DNA double-strand breaks. Recent studies with cells
derived from radiosensitive and immune-deficient patients have identified the
human protein, XLF (also named Cernunnos), as a crucial NHEJ protein. Here we
show that XLF and Nej1p are members of the same protein superfamily and that this
family has members in diverse eukaryotes. Indeed, we show that a member of this
family encoded by a previously uncharacterized open-reading frame in the
Schizosaccharomyces pombe genome is required for NHEJ in this organism.
Furthermore, our data reveal that XLF family proteins can bind to DNA and
directly interact with the ligase IV-XRCC4 complex to promote DSB ligation. We
therefore conclude that XLF family proteins interact with the ligase IV-XRCC4
complex to constitute the evolutionarily conserved enzymatic core of the NHEJ
machinery.
PMID- 17038310
TI - Structural and membrane binding analysis of the Phox homology domain of
phosphoinositide 3-kinase-C2alpha.
AB - Phox homology (PX) domains, which have been identified in a variety of proteins
involved in cell signaling and membrane trafficking, have been shown to interact
with phosphoinositides (PIs) with different affinities and specificities. To
elucidate the structural origin of diverse PI specificities of PX domains, we
determined the crystal structure of the PX domain from phosphoinositide 3-kinase
C2alpha (PI3K-C2alpha), which binds phosphatidylinositol 4,5-bisphosphate
(PtdIns(4,5)P(2)). To delineate the mechanism by which this PX domain interacts
with membranes, we measured the membrane binding of the wild type domain and
mutants by surface plasmon resonance and monolayer techniques. This PX domain
contains a signature PI-binding site that is optimized for PtdIns(4,5)P(2)
binding. The membrane binding of the PX domain is initiated by nonspecific
electrostatic interactions followed by the membrane penetration of hydrophobic
residues. Membrane penetration is specifically enhanced by PtdIns(4,5)P(2).
Furthermore, the PX domain displayed significantly higher PtdIns(4,5)P(2)
membrane affinity and specificity when compared with the PI3K-C2alpha C2 domain,
demonstrating that high affinity PtdIns(4,5)P(2) binding was facilitated by the
PX domain in full-length PI3K-C2alpha. Together, these studies provide new
structural insight into the diverse PI specificities of PX domains and elucidate
the mechanism by which the PI3K-C2alpha PX domain interacts with PtdIns(4,5)P(2)
containing membranes and thereby mediates the membrane recruitment of PI3K
C2alpha.
PMID- 17038311
TI - Proline-rich motifs in the parathyroid hormone (PTH)/PTH-related protein receptor
C terminus mediate scaffolding of c-Src with beta-arrestin2 for ERK1/2
activation.
AB - Parathyroid hormone (PTH) stimulates ERK1/2 through both G-protein signaling and
beta-arrestin2-mediated internalization. Beta-arrestin may serve as a scaffold
for c-Src. However, the molecular mechanisms for ERK1/2 activation by PTH remain
unclear. By using a targeted mutagenesis approach, we investigated the PTH/PTH
related protein receptor (PTH1R) structural determinants for ERK1/2 activation
and transcriptional activity in HEK-293 cells. First, ERK1/2 activation was
inhibited by PTH1R mutations that specifically abrogate G(q)-protein kinase C
signaling without a decrease in cAMP-protein kinase A. Second, PTH1R C-terminal
mutations and/or deletions that prevent interaction with beta-arrestin inhibited
ERK1/2 activation. Similar results were obtained in HEK-293 cells co-expressing
wild-type PTH1R and a dominant-negative beta-arrestin2. Third, the c-Src
inhibitor PP2 and a kinase-dead c-SrcK295M mutant co-expressed with wild-type
PTH1R both inhibited ERK1/2 activation. Furthermore, c-Src co-precipitated with
both PTH1R and beta-arrestin2 in response to PTH. Deleting the PTH1R-proximal C
terminus abolished these interactions. However, the need for receptor interaction
with beta-arrestin to co-precipitate Src and activate ERK1/2 was obviated by
expressing a constitutively active c-SrcY527A mutant, suggesting direct binding
of activated Src to PTH1R. Subsequently, we identified and mutated to alanine
four proline-rich motifs in the PTH1R distal C terminus, which resulted in loss
of both c-Src and arrestin co-precipitation and significantly decreased ERK1/2
activation. These data delineate the multiple PTH1R structural determinants for
ERK1/2 activation and newly identify a unique mechanism involving proline-rich
motifs in the receptor C terminus for reciprocal scaffolding of c-Src and beta
arrestin2 with a class II G-protein-coupled receptor.
PMID- 17038312
TI - Topology of the VirB4 C terminus in the Agrobacterium tumefaciens VirB/D4 type IV
secretion system.
AB - Gram-negative type IV secretion systems (T4SSs) transfer proteins and DNA to
eukaryotic and/or prokaryotic recipients resulting in pathogenesis or conjugative
DNA transfer. VirB4, one of the most conserved proteins in these systems, has
both energetic and structural roles in substrate translocation. We previously
predicted a structural model for the large C-terminal domain (residues 425-789)
of VirB4 of Agrobacterium tumefaciens. Here we have defined a homology-based
structural model for Agrobacterium VirB11. Both VirB4 and VirB11 models predict
hexameric oligomers. Yeast two-hybrid interactions define peptides in the C
terminus of VirB4 and the N terminus of VirB11 that interact with each other.
These interactions were mapped onto the homology models to predict direct
interactions between the hexameric interfaces of VirB4 and VirB11 such that the
VirB4 C terminus stacks above VirB11 in the periplasm. In support of this,
fractionation and Western blotting show that the VirB4 C terminus is localized to
the membrane and periplasm rather than the cytoplasm of cells. Additional high
resolution yeast two-hybrid results demonstrate interactions between the C
terminus of VirB4 and the periplasmic portions of VirB1, VirB8, and VirB10.
Genetic studies reveal dominant negative interactions and thus function of the
VirB4 C terminus in vivo. The above data are integrated with the existing body of
literature to propose a structural, periplasmic role for the C-terminal half of
the Agrobacterium VirB4 protein.
PMID- 17038313
TI - Protein kinase C-dependent enhancement of activity of rat brain NCKX2
heterologously expressed in HEK293 cells.
AB - Different members of the Na+/Ca2++K+ exchanger (NCKX) family are present in
distinct brain regions, suggesting that they may have cell-specific functions.
Many neuronal channels and transporters are regulated via phosphorylation.
Regulation of the rat brain NCKXs by protein kinases, however, has not been
described. Here, we report an increase in NCKX2 activity in response to protein
kinase C (PKC) activation. Outward current of NCKX2 heterologously expressed in
HEK293 cells was enhanced by beta-phorbol dibutyrate (PDBu), whereas PDBu had
little effect on activity of NCKX3 or NCKX4. The PDBu-induced enhancement (PIE)
of NCKX2 activity was abolished by PKC inhibitors and significantly reduced when
the dominant negative mutant of PKCepsilon (K437R) was overexpressed. Moreover,
PDBu accelerated the decay rate of the Ca2+ transient at the calyx of Held, where
NCKX is the major Ca2+-clearance mechanism. Intracellular perfusion with alkaline
phosphatase completely inhibited PIE. Consistently, beta-phorbol myristate
acetate (PMA), but not 4alpha-PMA, induced a 3-fold stimulation of 32P
incorporation into NCKX2 expressed in HEK293 cells. To investigate the sites
involved, PIE of wild-type NCKX2 was compared with mutant NCKX2 in which the
three putative PKC consensus sites were replaced with alanine, either
individually or in combination. Double-site mutation involving Thr-476
(T166A/T476A and T476A/S504A) disrupted PIE, whereas single mutation of Thr-166,
Thr-476, or Ser-504 or the double mutant T166A/S504A failed to completely prevent
PIE. These findings suggest that PKC-mediated activation of NCKX2 is sensitive to
mutation of multiple PKC consensus sites via a mechanism that may involve several
phosphorylation events.
PMID- 17038314
TI - SNARE status regulates tether recruitment and function in homotypic COPII vesicle
fusion.
AB - In mammals, coat complex II (COPII)-coated transport vesicles deliver secretory
cargo to vesicular tubular clusters (VTCs) that facilitate cargo sorting and
transport to the Golgi. We documented in vitro tethering and SNARE-dependent
homotypic fusion of endoplasmic reticulum-derived COPII transport vesicles to
form larger cargo containers characteristic of VTCs ( Xu, D., and Hay, J. C.
(2004) J. Cell Biol. 167, 997-1003). COPII vesicles thus appear to contain all
necessary components for homotypic tethering and fusion, providing a pathway for
de novo VTC biogenesis. Here we demonstrate that antibodies against the
endoplasmic reticulum/Golgi SNARE Syntaxin 5 inhibit COPII vesicle homotypic
tethering as well as fusion, implying an unanticipated role for SNAREs upstream
of fusion. Inhibition of SNARE complex access and/or disassembly with dominant
negative alpha-soluble NSF attachment protein (SNAP) also inhibited tethering,
implicating SNARE status as a critical determinant in COPII vesicle tethering.
The tethering-defective vesicles generated in the presence of dominant-negative
alpha-SNAP specifically lacked the Rab1 effectors p115 and GM130 but not other
peripheral membrane proteins. Furthermore, Rab effectors, including p115, were
shown to be required for homotypic COPII vesicle tethering. Thus, our results
demonstrate a requirement for SNARE-dependent tether recruitment and function in
COPII vesicle fusion. We anticipate that recruitment of tether molecules by an
upstream SNARE signal ensures that tethering events are initiated only at focal
sites containing appropriately poised fusion machinery.
PMID- 17038315
TI - Inhibition of Escherichia coli heat-labile enterotoxin B subunit pentamer (EtxB5)
assembly in vitro using monoclonal antibodies.
AB - Heat-labile enterotoxin (Etx) produced by certain strains of Escherichia coli is
a major virulence factor related to cholera toxin. Both are hexameric proteins
comprising one A-subunit and five B-subunits. The pentameric B-subunit of E. coli
has a high affinity for G(M1)-ganglioside receptors on gut epithelial cells and
is directly responsible for toxin entry. The pentameric B-subunit (EtxB(5)) is an
exceptionally stable protein, being able to maintain its quaternary structure
over a wide pH range (2.0- 11.0). However, little is known about the formation of
the pentameric structure (EtxB(5)) from newly synthesized B-subunit monomers
(EtxB(1)). We previously described and characterized a mAb (LDS47) that was shown
to be highly specific for an N-terminal decapeptide region of EtxB(1) (Amin, T.,
Larkins, A., James, R. F. L., and Hirst, T. R. (1995) J. Biol. Chem. 270, 20143
20150). Here we also describe a mAb (LDS16) with exquisite specificity for
pentameric EtxB. In this study, we have used these two mAbs, in combination, to
probe the in vitro assembly of EtxB(5) from EtxB(1). EtxB pentamers disassemble
in highly acidic conditions, giving rise to monomeric B-subunits that can
reassemble if placed in buffers of neutral pH. Using this in vitro assembly
model, it was found that at a molar ratio of 1:1; LDS47:EtxB, 50% of reassembly
was inhibited, and that this inhibition increased to 90% at a ratio of 2:1. These
results infer that the N-terminal decapeptide region (APQSITELCS) defined by the
LDS47 antibody is crucial for competent pentameric B-subunit assembly and
stabilization.
PMID- 17038316
TI - Regulation of anterograde transport of alpha2-adrenergic receptors by the N
termini at multiple intracellular compartments.
AB - The studies on the intrinsic structural determinants for export trafficking of G
protein-coupled receptors (GPCRs) have been mainly focused on the C termini of
the receptors. In this report we determined the role of the extracellular N
termini of alpha(2)-adrenergic receptors (alpha(2)-ARs) in the anterograde
transport from the endoplasmic reticulum (ER) through the Golgi to the cell
surface. The N-terminal-truncated alpha(2B)-AR mutant is completely unable to
target to the cell surface. A single Met-6 residue is essential for the export of
alpha(2B)-AR from the ER, likely through modulating correct alpha(2B)-AR folding
in the ER. The Tyr-Ser motif, highly conserved in the membrane-proximal N termini
of all alpha(2)-AR subtypes, is required for the exit of alpha(2A)-AR and
alpha(2B)-AR from the Golgi apparatus, thus representing a novel Tyr-based motif
modulating GPCR transport at the Golgi level. These data provide the first
evidence indicating an essential role of the N termini of GPCRs in the export
from distinct intracellular compartments along the secretory pathway.
PMID- 17038317
TI - Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas.
AB - We previously showed that activation of the small GTPase Cdc42 promotes breast
cell migration on a collagen matrix. Here we further define the signaling
pathways that drive this response and show that Cdc42-mediated migration relies
on the adaptor molecule p130(Cas). Activated Cdc42 enhanced p130(Cas)
phosphorylation and its binding to Crk. Cdc42-driven migration and p130(Cas)
phosphorylation were dependent on the Cdc42 effector Ack1 (activated Cdc42
associated kinase). Ack1 formed a signaling complex that also included Cdc42,
p130(Cas), and Crk, formation of which was regulated by collagen stimulation. The
interaction between Ack1 and p130(Cas) occurred through their respective SH3
domains, while the substrate domain of p130(Cas) was the major site of Ack1
dependent phosphorylation. Signaling through this complex is functionally
relevant, because treatment with either p130(Cas) or Ack1 siRNA blocked Cdc42
induced migration. These results suggest that Cdc42 exerts its effects on cell
migration in part through its effector Ack1, which regulates p130(Cas) signaling.
PMID- 17038318
TI - A Chinese hamster ovarian cell line imports cholesterol by high density
lipoprotein degradation.
AB - Plasma high density lipoprotein (HDL) is inversely associated with the
development of atherosclerosis. HDL exerts its atheroprotective role through
involvement in reverse cholesterol transport in which HDL is loaded with
cholesterol at the periphery and transports its lipid load back to the liver for
disposal. In this pathway, HDL is not completely dismantled but only transfers
its lipids to the cell. Here we present evidence that a Chinese hamster ovarian
cell line (CHO7) adapted to grow in lipoprotein-deficient media degrades HDL and
concomitantly internalizes HDL-derived cholesterol. Delivery of HDL cholesterol
to the cell was demonstrated by a down-regulation of cholesterol biosynthesis, an
increase in total cellular cholesterol content and by stimulation of cholesterol
esterification after HDL treatment. This HDL degradation pathway is distinct from
the low density lipoprotein (LDL) receptor pathway but also degrades LDL. 25
Hydroxycholesterol, a potent inhibitor of the LDL receptor pathway, down
regulated LDL degradation in CHO7 cells only in part and did not down-regulate
HDL degradation. Dextran sulfate released HDL bound to the cell surface of CHO7
cells, and heparin treatment released protein(s) contributing to HDL degradation.
The involvement of heparan sulfate proteoglycans and lipases in this HDL
degradation was further tested by two inhibitors genistein and
tetrahydrolipstatin. Both blocked HDL degradation significantly. Thus, we
demonstrate that CHO7 cells degrade HDL and LDL to supply themselves with
cholesterol via a novel degradation pathway. Interestingly, HDL degradation with
similar properties was also observed in a human placental cell line.
PMID- 17038319
TI - Fragmented hyaluronan induces transcriptional up-regulation of the multidrug
resistance-1 gene in CD4+ T cells.
AB - P-glycoprotein, encoded by the multidrug resistance (MDR)-1 gene, expels various
drugs from cells resulting in multidrug resistance. We found previously that
interleukin-2, a lymphocyte-activation cytokine, induces P-glycoprotein
expression on lymphocytes. Lymphocyte activation involves adhesion with the
extracellular matrix, such as hyaluronan, through adhesion molecules on
lymphocytes. We investigated the transcriptional regulation of MDR-1 in
lymphocytes by fragmented hyaluronan. Fragmented hyaluronan (especially the 6.9
kDa form), not native high molecular hyaluronan, induced translocation of YB-1, a
specific transcriptional factor for MDR-1, from the cytoplasm into the nucleus
and resulted in the transcription of MDR-1 and the expression of P-glycoprotein
on lymphocytes in a dose-dependent manner. Transfection of YB-1 antisense
oligonucleotides inhibited P-glycoprotein expression induced by fragmented
hyaluronan. The fragmented hyaluronan induced significant P-glycoprotein
expression on only activated CD4+ T cells, which highly expressed CD69, and
resulted in excretion of intracellular dexamethasone added in vitro. Cyclosporin
A, a competitive P-glycoprotein inhibitor, restored intracellular dexamethasone
levels in CD4+ T cells. Anti-CD44 monoclonal antibody (Hermes-1) inhibited
fragmented hyaluronan-induced YB-1 activation and P-glycoprotein expression in
CD4+ T cells. We provide the first evidence that binding of fragmented hyaluronan
to CD44 induces YB-1 activation followed by P-glycoprotein expression in
accordance with activation of CD4+ T cells. Our findings imply that CD4+ T cell
activation by fragmented hyaluronan, induced by characteristic extracellular
matrix changes in inflammation, tumors, and other conditions, results in P
glycoprotein-mediated multidrug resistance.
PMID- 17038320
TI - A three-dimensional model of human organic anion transporter 1: aromatic amino
acids required for substrate transport.
AB - Organic anion transporters (OATs) play a critical role in the handling of
endogenous and exogenous organic anions by excretory and barrier tissues. Little
is known about the OAT three-dimensional structure or substrate/protein
interactions involved in transport. In this investigation, a theoretical three
dimensional model was generated for human OAT1 (hOAT1) based on fold recognition
to the crystal structure of the glycerol 3-phosphate transporter (GlpT) from
Escherichia coli. GlpT and hOAT1 share several sequence motifs as major
facilitator superfamily members. The structural hOAT1 model shows that helices 5,
7, 8, 10, and 11 surround an electronegative putative active site ( approximately
830A(3)). The site opens to the cytoplasm and is surrounded by three residues not
previously examined for function (Tyr(230) (domain 5) and Lys(431) and Phe(438)
(domain 10)). Effects of these residues on p-aminohippurate (PAH) and cidofovir
transport were assessed by point mutations in a Xenopus oocyte expression system.
Membrane protein expression was severely limited for the Y230A mutant. For the
K431A and F438A mutants, [(3)H]PAH uptake was less than 30% of wild-type hOAT1
uptake after protein expression correction. Reduced V(max) values for the F438A
mutant confirmed lower protein expression. In addition, the F438A mutant
exhibited an increased affinity for cidofovir but was not significantly different
for PAH. Differences in handling of PAH and cidofovir were also observed for the
Y230F mutant. Little uptake was determined for cidofovir, whereas PAH uptake was
similar to wild-type hOAT1. Therefore, the hOAT1 structural model has identified
two new residues, Tyr(230) and Phe(438), which are important for
substrate/protein interactions.
PMID- 17038321
TI - The role of the GX9GX3G motif in the gating of high voltage-activated Ca2+
channels.
AB - The putative hinge point revealed by the crystal structure of the MthK potassium
channel is a glycine residue that is conserved in many ion channels. In high
voltage-activated (HVA) Ca(V) channels, the mid-S6 glycine residue is only
present in IS6 and IIS6, corresponding to G422 and G770 in Ca(V)1.2. Two
additional glycine residues are found in the distal portion of IS6 (Gly(432) and
Gly(436) in Ca(V)1.2) to form a triglycine motif unique to HVA Ca(V) channels.
Lethal arrhythmias are associated with mutations of glycine residues in the human
L-type Ca(2+) channel. Hence, we undertook a mutational analysis to investigate
the role of S6 glycine residues in channel gating. In Ca(V)1.2, alpha-helix
breaking proline mutants (G422P and G432P) as well as the double G422A/G432A
channel did not produce functional channels. The macroscopic inactivation
kinetics were significantly decreased with Ca(V)1.2 wild type > G770A > G422A
congruent with G436A >> G432A (from the fastest to the slowest). Mutations at
position Gly(432) produced mostly nonfunctional mutants. Macroscopic inactivation
kinetics were markedly reduced by mutations of Gly(436) to Ala, Pro, Tyr, Glu,
Arg, His, Lys, or Asp residues with stronger effects obtained with charged and
polar residues. Mutations within the distal GX(3)G residues blunted Ca(2+)
dependent inactivation kinetics and prevented the increased voltage-dependent
inactivation kinetics brought by positively charged residues in the I-II linker.
In Ca(V)2.3, mutation of the distal glycine Gly(352) impacted significantly on
the inactivation gating. Altogether, these data highlight the role of the GX(3)G
motif in the voltage-dependent activation and inactivation gating of HVA Ca(V)
channels with the distal glycine residue being mostly involved in the
inactivation gating.
PMID- 17038322
TI - Flap endonuclease disengages Dna2 helicase/nuclease from Okazaki fragment flaps.
AB - Okazaki fragments contain an initiator RNA/DNA primer that must be removed before
the fragments are joined. In eukaryotes, the primer region is raised into a flap
by the strand displacement activity of DNA polymerase delta. The Dna2
helicase/nuclease and then flap endonuclease 1 (FEN1) are proposed to act
sequentially in flap removal. Dna2 and FEN1 both employ a tracking mechanism to
enter the flap 5' end and move toward the base for cleavage. In the current
model, Dna2 must enter first, but FEN1 makes the final cut at the flap base,
raising the issue of how FEN1 passes the Dna2. To address this, nuclease-inactive
Dna2 was incubated with a DNA flap substrate and found to bind with high
affinity. FEN1 was then added, and surprisingly, there was little inhibition of
FEN1 cleavage activity. FEN1 was later shown, by gel shift analysis, to remove
the wild type Dna2 from the flap. RNA can be cleaved by FEN1 but not by Dna2. Pre
bound wild type Dna2 was shown to bind an RNA flap but not inhibit subsequent
FEN1 cleavage. These results indicate that there is a novel interaction between
the two proteins in which FEN1 disengages the Dna2 tracking mechanism. This
interaction is consistent with the idea that the two proteins have evolved a
special ability to cooperate in Okazaki fragment processing.
PMID- 17038323
TI - Association of Kv1.5 and Kv1.3 contributes to the major voltage-dependent K+
channel in macrophages.
AB - Voltage-dependent K(+) (Kv) currents in macrophages are mainly mediated by Kv1.3,
but biophysical properties indicate that the channel composition could be
different from that of T-lymphocytes. K(+) currents in mouse bone marrow-derived
and Raw-264.7 macrophages are sensitive to Kv1.3 blockers, but unlike T-cells,
macrophages express Kv1.5. Because Shaker subunits (Kv1) may form
heterotetrameric complexes, we investigated whether Kv1.5 has a function in Kv
currents in macrophages. Kv1.3 and Kv1.5 co-localize at the membrane, and half
activation voltages and pharmacology indicate that K(+) currents may be accounted
for by various Kv complexes in macrophages. Co-expression of Kv1.3 and Kv1.5 in
human embryonic kidney 293 cells showed that the presence of Kv1.5 leads to a
positive shift in K(+) current half-activation voltages and that, like Kv1.3,
Kv1.3/Kv1.5 heteromers are sensitive to r-margatoxin. In addition, both proteins
co-immunoprecipitate and co-localize. Fluorescence resonance energy transfer
studies further demonstrated that Kv1.5 and Kv1.3 form heterotetramers.
Electrophysiological and pharmacological studies of different ratios of Kv1.3 and
Kv1.5 co-expressed in Xenopus oocytes suggest that various hybrids might be
responsible for K(+) currents in macrophages. Tumor necrosis factor-alpha-induced
activation of macrophages increased Kv1.3 with no changes in Kv.1.5, which is
consistent with a hyperpolarized shift in half-activation voltage and a lower
IC(50) for margatoxin. Taken together, our results demonstrate that Kv1.5 co
associates with Kv1.3, generating functional heterotetramers in macrophages.
Changes in the oligomeric composition of functional Kv channels would give rise
to different biophysical and pharmacological properties, which could determine
specific cellular responses.
PMID- 17038324
TI - Murine leukemia virus regulates alternative splicing through sequences upstream
of the 5' splice site.
AB - Alternative splicing of the primary transcript plays a key role in retroviral
gene expression. In contrast to all known mechanisms that mediate alternative
splicing in retroviruses, we found that in murine leukemia virus, distinct
elements located upstream of the 5' splice site either inhibited or activated
splicing of the genomic RNA. Detailed analysis of the first untranslated exon
showed that the primer binding site (PBS) activates splicing, whereas flanking
sequences either downstream or upstream of the PBS are inhibitory. This new
function of the PBS was independent of its orientation and primer binding but
associated with a particular destabilizing role in a proposed secondary
structure. On the contrary, all sequences surrounding the PBS that are involved
in stem formation of the first exon were found to suppress splicing. Targeted
mutations that destabilized the central stem and compensatory mutations of the
counter strand clearly validated the concept that murine leukemia virus
attenuates its 5' splice site by forming an inhibitory stem-loop in its first
exon. Importantly, this mode of splice regulation was conserved in a complete
proviral clone. Some of the mutants that increase splicing revealed an opposite
effect on translation, implying that the first exon also regulates this process.
Together, these findings suggest that sequences upstream of the 5' splice site
play an important role in splice regulation of simple retroviruses, directly or
indirectly attenuating the efficiency of splicing.
PMID- 17038325
TI - Combined leptin actions on adipose tissue and hypothalamus are required to
deplete adipocyte fat in lean rats: implications for obesity treatment.
AB - Intense hyperleptinemia completely depletes adipocyte fat of normal rats within
14 days. To determine the mechanism, epididymal fat pads from normal wild-type
(+/+) and obese (fa/fa) Zucker Diabetic Fatty (ZDF) donor rats were transplanted
into normal +/+ and fa/fa ZDF recipients. Hyperleptinemia induced by adenovirus
leptin administration depleted all fat from native fat pads and from fat
transplants from +/+ donors but not from transplants from ZDF(fa/fa) donors with
defective leptin receptors. In both native and transplanted +/+ fat pads, large
numbers of mitochondria were apparent, and genes involved in fatty acid oxidation
were up-regulated. However, +/+ fat pads transplanted into fa/fa recipients did
not respond to hyperleptinemia, suggesting lack of an essential leptin-stimulated
cohormone(s). In +/+ but not in fa/fa rats, plasma catecholamine levels rose, and
both P-STAT3 and P-CREB increased in adipose tissue, suggesting that both direct
and indirect (hypothalamic) leptin receptor-mediated actions of hyperleptinemia
are involved in depletion of adipocyte fat.
PMID- 17038326
TI - Cyclic GMP-dependent protein kinase Ialpha attenuates necrosis and apoptosis
following ischemia/reoxygenation in adult cardiomyocyte.
AB - Cyclic GMP-dependent protein kinases protein kinase G (PKG) Ialpha and PKGIbeta
are major mediators of cGMP signaling in the cardiovascular system. PKGIalpha is
present in the heart, although its role in protection against
ischemia/reperfusion injury is not known. We investigated the direct effect of
PKGIalpha against necrosis and apoptosis following simulated ischemia (SI) and
reoxygenation (RO) in cardiomyocytes. Adult rat cardiomyocytes were infected with
adenoviral vectors containing hPKGIalpha or catalytically inactive mutant
hPKGIalphaK390A. After 24 h, the cells were subjected to 90 min of SI and 2 h RO
for necrosis (trypan blue exclusion and lactate dehydrogenase release) or 18 h RO
for apoptosis studies. To evaluate the role of K(ATP) channels, subgroups of
cells were treated with 5-hydroxydecanoate (100 microm), HMR1098 (30 microm), or
glibenclamide (50 microm), the respective blockers of mitochondrial, sarcolemmal,
or both types of K(ATP) channels prior to SI. The necrosis observed in 33.7 +/-
1.6% of total myocytes in the SI-RO control group was reduced to 18.6 +/- 0.8% by
PKGIalpha (mean +/- S.E., n = 7, p < 0.001). The apoptosis observed in 17.9 +/-
1.3% of total myocytes in the SI-RO control group was reduced to 6.0 +/- 0.6% by
PKGIalpha (mean +/- S.E., n = 7, p < 0.001). In addition, PKGIalpha inhibited the
activation of caspase-3 after SI-RO in myocytes. Myocytes infected with the
inactive PKGIalphaK390A mutant showed no protection. PKGIalpha enhanced
phosphorylation of Akt, ERK1/2, and JNK, increased Bcl-2, inducible nitric-oxide
synthase, endothelial nitric-oxide synthase, and decreased Bax expression. 5
Hydroxydecanoate and glibenclamide abolished PKGIalpha-mediated protection
against necrosis and apoptosis. However, HMR1098, had no effect. A scavenger of
reactive oxygen species, as well as inhibitors of phosphatidylinositol 3-kinase,
ERK, JNK1, and NOS, also blocked PKGIalpha-mediated protection against necrosis
and apoptosis. These results show that opening of mitochondrial K(ATP) channels
and generation of reactive oxygen species, in association with phosphorylation of
Akt, ERK, and JNK, and increased expression of NOS and Bcl-2, play an essential
role in the protective effect of PKGIalpha.
PMID- 17038327
TI - The ubiquitin ligase itch is auto-ubiquitylated in vivo and in vitro but is
protected from degradation by interacting with the deubiquitylating enzyme
FAM/USP9X.
AB - Itch is a ubiquitin ligase that has been implicated in the regulation of a number
of cellular processes. We previously have identified Itch as a binding partner
for the endocytic protein Endophilin and found it to be localized to endosomes.
Using affinity purification coupled to mass spectrometry, we have now identified
the ubiquitin-protease FAM/USP9X as a binding partner of Itch. The association
between Itch and FAM/USP9X was confirmed in vitro by glutathione S-transferase
pulldown and in vivo through coimmunoprecipation. Itch and FAM partially
colocalize in COS-7 cells at the trans-Golgi network and in peripheral vesicles.
We mapped the FAM-binding domain on Itch to the WW domains, a region known to be
involved in substrate recognition. However, transient overexpression of FAM/USP9X
resulted in the deubiquitylation of Itch. Moreover, we show that Itch auto
ubiquitylation leads to its degradation in the proteasome. By examining the
amounts of Itch and FAM in various cell lines and rat tissues, a positive
correlation was found in the expression of both proteins. This observation
suggests that the levels of FAM expression could have an influence on Itch in
cells. Experimental decrease in FAM levels by RNA interference leads to a
significant reduction in intracellular levels of endogenous Itch, which can be
prevented by treatment with the proteasome inhibitor lactacystin. Accordingly,
overexpression of FAM/USP9X resulted in a marked increase in endogenous Itch
levels. These results demonstrate an intriguing interplay between a ubiquitin
ligase and a ubiquitin protease, based on direct interaction between the two
proteins.
PMID- 17038328
TI - Protein kinase CK2 is inhibited by human nucleolar phosphoprotein p140 in an
inositol hexakisphosphate-dependent manner.
AB - Protein kinase CK2 is a ubiquitous protein kinase that can phosphorylate various
proteins involved in central cellular processes, such as signal transduction,
cell division, and proliferation. We have shown that the human nucleolar
phosphoprotein p140 (hNopp140) is able to regulate the catalytic activity of CK2.
Unphosphorylated hNopp140 and phospho-hNopp140 bind to the regulatory and
catalytic subunits of CK2, respectively, and the interaction between hNopp140 and
CK2 was prevented by inositol hexakisphosphate (InsP(6)). Phosphorylation of
alpha-casein, genimin, or human phosphatidylcholine transfer protein-like protein
by CK2 was inhibited by hNopp140, and InsP(6) recovered the suppressed activity
of CK2 by hNopp140. These observations indicated that hNopp140 serves as a
negative regulator of CK2 and that InsP(6) stimulates the activity of CK2 by
blocking the interaction between hNopp140 and CK2.
PMID- 17038329
TI - Audit-based education to reduce suboptimal management of cholesterol in primary
care: a before and after study.
AB - BACKGROUND: Statins are recommended for the secondary prevention of
cardiovascular disease, although they are often used in suboptimal doses and some
patients may not receive lipid-lowering therapy. The Primary Care Data Quality
(PCDQ) programme is an audit-based educational intervention. OBJECTIVE: To report
the PCDQ programme's effect on the cholesterol management in cardiovascular
disease. Subjects and methods Anonymized general practice data from 99 practices;
5% (n = 29 915) had cardiovascular diagnoses. RESULTS: Mean cholesterol fell from
4.75 to 4.64 mmol l(-1); patients achieving cholesterol target (< 5 mmol l(-1))
rose from 45.3 to 53.2%. Coronary heart disease patients achieved better control
(mean 4.57 mmol l(-1)) than those with stroke (4.87 mmol l(-1)) or peripheral
vascular disease (4.93 mmol l(-1)). Statin prescribing increased from 57.5 to
62.7%. Patients with diabetes [odds ratio (OR) 2.06, 95% confidence interval (95%
CI) 1.91-2.21], prior myocardial infarction (MI) (OR 1.93, 95% CI 1.80-2.07),
revascularization (OR 1.52, 95% CI 1.33-1.73) and smokers (OR 1.31, 95% CI 1.23
1.39) were more likely to receive statins, whereas people aged 75+ (OR 0.48, 95%
CI 0.45-0.50), females (OR 0.90, 95% CI 0.86-0.94) and non-CHD-diagnosed (OR
0.36, 95% CI 0.34-0.38) were less likely. CONCLUSIONS: Diagnostic coding and
number of patients who had their cholesterol measured and treated increased.
There was no significant change in dosage used or inequity between the different
groups prescribed statins.
PMID- 17038330
TI - Evolutionarily conserved and non-conserved retrovirus restriction activities of
artiodactyl APOBEC3F proteins.
AB - The APOBEC3 proteins are unique to mammals. Many inhibit retrovirus infection
through a cDNA cytosine deamination mechanism. HIV-1 neutralizes this host
defense through Vif, which triggers APOBEC3 ubiquitination and degradation. Here,
we report an APOBEC3F-like, double deaminase domain protein from three
artiodactyls: cattle, pigs and sheep. Like their human counterparts, APOBEC3F and
APOBEC3G, the artiodactyl APOBEC3F proteins are DNA cytosine deaminases that
locate predominantly to the cytosol and can inhibit the replication of HIV-1 and
MLV. Retrovirus restriction is attributable to deaminase-dependent and
independent mechanisms, as deaminase-defective mutants retain significant anti
retroviral activity. However, unlike human APOBEC3F and APOBEC3G, the artiodactyl
APOBEC3F proteins have an active N-terminal DNA cytosine deaminase domain, which
elicits a broader dinucleotide deamination preference, and they are resistant to
HIV-1 Vif. These data indicate that DNA cytosine deamination; sub-cellular
localization and retrovirus restriction activities are conserved in mammals,
whereas active site location, local mutational preferences and Vif susceptibility
are not. Together, these studies indicate that some properties of the mammal
specific, APOBEC3-dependent retroelement restriction system are necessary and
conserved, but others are simultaneously modular and highly adaptable.
PMID- 17038331
TI - Codeine-binding RNA aptamers and rapid determination of their binding constants
using a direct coupling surface plasmon resonance assay.
AB - RNA aptamers that bind the opium alkaloid codeine were generated using an
iterative in vitro selection process. The binding properties of these aptamers,
including equilibrium and kinetic rate constants, were determined through a
rapid, high-throughput approach using surface plasmon resonance (SPR) analysis to
measure real-time binding. The approach involves direct coupling of the target
small molecule onto a sensor chip without utilization of a carrier protein. Two
highest binding aptamer sequences, FC5 and FC45 with K(d) values of 2.50 and 4.00
microM, respectively, were extensively studied. Corresponding mini-aptamers for
FC5 and FC45 were subsequently identified through the described direct coupling
Biacore assays. These assays were also employed to confirm the proposed secondary
structures of the mini-aptamers. Both aptamers exhibit high specificity to
codeine over morphine, which differs from codeine by a methyl group. Finally, the
direct coupling method was demonstrated to eliminate potential non-specific
interactions that may be associated with indirect coupling methods in which
protein linkers are commonly employed. Therefore, in addition to presenting the
first RNA aptamers to a subclass of benzylisoquinoline alkaloid molecules, this
work highlights a method for characterizing small molecule aptamers that is more
robust, precise, rapid and high-throughput than other commonly employed
techniques.
PMID- 17038332
TI - Rational design and rapid screening of antisense oligonucleotides for prokaryotic
gene modulation.
AB - Antisense oligodeoxynucleotides (oligos) are widely used for functional studies
of both prokaryotic and eukaryotic genes. However, the identification of
effective target sites is a major issue in antisense applications. Here, we study
a number of thermodynamic and structural parameters that may affect the potency
of antisense inhibition. We develop a cell-free assay for rapid oligo screening.
This assay is used for measuring the expression of Escherichia coli lacZ, the
antisense target for experimental testing and validation. Based on a training set
of 18 oligos, we found that structural accessibility predicted by local folding
of the target mRNA is the most important predictor for antisense activity. This
finding was further confirmed by a direct validation study. In this study, a set
of 10 oligos was designed to target accessible sites, and another set of 10
oligos was selected to target inaccessible sites. Seven of the 10 oligos for
accessible sites were found to be effective (>50% inhibition), but none of the
oligos for inaccessible sites was effective. The difference in the antisense
activity between the two sets of oligos was statistically significant. We also
found that the predictability of antisense activity by target accessibility was
greatly improved for oligos targeted to the regions upstream of the end of the
active domain for beta-galactosidase, the protein encoded by lacZ. The
combination of the structure-based antisense design and extension of the lacZ
assay to include gene fusions will be applicable to high-throughput gene
functional screening, and to the identification of new drug targets in pathogenic
microbes. Design tools are available through the Sfold Web server at
http://sfold.wadsworth.org.
PMID- 17038333
TI - Indirect readout: detection of optimized subsequences and calculation of relative
binding affinities using different DNA elastic potentials.
AB - Essential biological processes require that proteins bind to a set of specific
DNA sites with tuned relative affinities. We focus on the indirect readout
mechanism and discuss its theoretical description in relation to the present
understanding of DNA elasticity on the rigid base pair level. Combining existing
parametrizations of elastic potentials for DNA, we derive elastic free energies
directly related to competitive binding experiments, and propose a
computationally inexpensive local marker for elastically optimized subsequences
in protein-DNA co-crystals. We test our approach in an application to the
bacteriophage 434 repressor. In agreement with known results we find that
indirect readout dominates at the central, non-contacted bases of the binding
site. Elastic optimization involves all deformation modes and is mainly due to
the adapted equilibrium structure of the operator, while sequence-dependent
elasticity plays a minor role. These qualitative observations are robust with
respect to current parametrization uncertainties. Predictions for relative
affinities mediated by indirect readout depend sensitively on the chosen
parametrization. Their quantitative comparison with experimental data allows for
a critical evaluation of DNA elastic potentials and of the correspondence between
crystal and solution structures. The software written for the presented analysis
is included as Supplementary Data.
PMID- 17038334
TI - Troubleshooting coupled in vitro transcription-translation system derived from
Escherichia coli cells: synthesis of high-yield fully active proteins.
AB - Cell-free coupled transcription-translation systems with bacterial lysates are
widely used to synthesize recombinant proteins in amounts of several mg per ml.
By using reporter green fluorescence protein (GFP) we demonstrate that proteins
are synthesized with an unsatisfyingly low-active fraction of (50 +/- 20)%. One
reason is probably the T7 polymerase used, being up to eight times faster than
the intrinsic transcriptase and thus breaking the coupling between transcription
and translation in bacterial systems. The active fraction of the synthesized
protein was improved by using either a slower T7 transcriptase mutant or lowering
the incubation temperature to 20 degrees C. A drop of protein synthesis observed
after 7 h incubation time was not due to a shortage of nucleotide triphosphates,
but rather to a shortage of amino acids. Accordingly, a second addition of amino
acids after 10 h during an incubation at 20 degrees C led to synthesis of up to 4
mg/ml of GFP with virtually 100% activity.
PMID- 17038335
TI - Specific binding of a hexanucleotide to HIV-1 reverse transcriptase: a novel
class of bioactive molecules.
AB - Short oligonucleotides below 8-10 nt in length adopt relatively simple
structures. Accordingly, they represent interesting and so far unexplored lead
compounds as molecular tools and, potentially, for drug development as a rational
improvement of efficacy seem to be less complex than for other classes of longer
oligomeric nucleic acid. As a 'proof of concept', we describe the highly specific
binding of the hexanucleotide UCGUGU (Hex-S3) to human immunodeficiency virus
type 1 (HIV-1) reverse transcriptase (RT) as a model target. Ultraviolet (UV)
cross-linking studies and competition experiments with primer/template substrates
and a RT-directed aptamer suggest site-specific binding of Hex-S3 to the large
subunit (p66) of the viral enzyme. The affinity of 5.3 muM is related to
hexanucleotide-specific suppression of HIV-1 replication in human cells by up to
three orders of magnitude indicating that Hex-S3 exerts specific and biologically
relevant activity. Experimental evidence described here further suggests a
systematic hexamer array-based search for new tools for molecular biology and
novel lead compounds in nucleic acid-based drug development.
PMID- 17038338
TI - Measuring covariation in RNA alignments: physical realism improves information
measures.
AB - MOTIVATION: The importance of non-coding RNAs is becoming increasingly evident,
and often the function of these molecules depends on the structure. It is common
to use alignments of related RNA sequences to deduce the consensus secondary
structure by detecting patterns of co-evolution. A central part of such an
analysis is to measure covariation between two positions in an alignment. Here,
we rank various measures ranging from simple mutual information to more advanced
covariation measures. RESULTS: Mutual information is still used for secondary
structure prediction, but the results of this study indicate which measures are
useful. Incorporating more structural information by considering e.g. indels and
stacking improves accuracy, suggesting that physically realistic measures yield
improved predictions. This can be used to improve both current and future
programs for secondary structure prediction. The best measure tested is the
RNAalifold covariation measure modified to include stacking. AVAILABILITY:
Scripts, data and supplementary material can be found at
http://www.binf.ku.dk/Stinus_covariation
PMID- 17038336
TI - The key DNA-binding residues in the C-terminal domain of Mycobacterium
tuberculosis DNA gyrase A subunit (GyrA).
AB - As only the type II topoisomerase is capable of introducing negative
supercoiling, DNA gyrase is involved in crucial cellular processes. Although the
other domains of DNA gyrase are better understood, the mechanism of DNA binding
by the C-terminal domain of the DNA gyrase A subunit (GyrA-CTD) is less clear.
Here, we investigated the DNA-binding sites in the GyrA-CTD of Mycobacterium
tuberculosis gyrase through site-directed mutagenesis. The results show that
Y577, R691 and R745 are among the key DNA-binding residues in M.tuberculosis GyrA
CTD, and that the third blade of the GyrA-CTD is the main DNA-binding region in
M.tuberculosis DNA gyrase. The substitutions of Y577A, D669A, R691A, R745A and
G729W led to the loss of supercoiling and relaxation activities, although they
had a little effect on the drug-dependent DNA cleavage and decatenation
activities, and had no effect on the ATPase activity. Taken together, these
results showed that the GyrA-CTD is essential to DNA gyrase of M.tuberculosis,
and promote the idea that the M.tuberculosis GyrA-CTD is a new potential target
for drug design. It is the first time that the DNA-binding sites in GyrA-CTD have
been identified.
PMID- 17038340
TI - ssSNPer: identifying statistically similar SNPs to aid interpretation of genetic
association studies.
AB - ssSNPer is a novel user-friendly web interface that provides easy determination
of the number and location of untested HapMap SNPs, in the region surrounding a
tested HapMap SNP, which are statistically similar and would thus produce
comparable and perhaps more significant association results. Identification of
ssSNPs can have crucial implications for the interpretation of the initial
association results and the design of follow-up studies. AVAILABILITY:
http://fraser.qimr.edu.au/general/daleN/ssSNPer/
PMID- 17038339
TI - A supervised hidden markov model framework for efficiently segmenting tiling
array data in transcriptional and chIP-chip experiments: systematically
incorporating validated biological knowledge.
AB - MOTIVATION: Large-scale tiling array experiments are becoming increasingly common
in genomics. In particular, the ENCODE project requires the consistent
segmentation of many different tiling array datasets into 'active regions' (e.g.
finding transfrags from transcriptional data and putative binding sites from ChIP
chip experiments). Previously, such segmentation was done in an unsupervised
fashion mainly based on characteristics of the signal distribution in the tiling
array data itself. Here we propose a supervised framework for doing this. It has
the advantage of explicitly incorporating validated biological knowledge into the
model and allowing for formal training and testing. METHODOLOGY: In particular,
we use a hidden Markov model (HMM) framework, which is capable of explicitly
modeling the dependency between neighboring probes and whose extended version
(the generalized HMM) also allows explicit description of state duration density.
We introduce a formal definition of the tiling-array analysis problem, and
explain how we can use this to describe sampling small genomic regions for
experimental validation to build up a gold-standard set for training and testing.
We then describe various ideal and practical sampling strategies (e.g. maximizing
signal entropy within a selected region versus using gene annotation or known
promoters as positives for transcription or ChIP-chip data, respectively).
RESULTS: For the practical sampling and training strategies, we show how the size
and noise in the validated training data affects the performance of an HMM
applied to the ENCODE transcriptional and ChIP-chip experiments. In particular,
we show that the HMM framework is able to efficiently process tiling array data
as well as or better than previous approaches. For the idealized sampling
strategies, we show how we can assess their performance in a simulation framework
and how a maximum entropy approach, which samples sub-regions with very different
signal intensities, gives the maximally performing gold-standard. This latter
result has strong implications for the optimum way medium-scale validation
experiments should be carried out to verify the results of the genome-scale
tiling array experiments.
PMID- 17038341
TI - NMPP: a user-customized NimbleGen microarray data processing pipeline.
AB - NMPP package is a bundle of user-customized tools based on established algorithms
and methods to process self-designed NimbleGen microarray data. It features a
command-line-based integrative processing procedure that comprises five major
functional components, namely the raw microarray data parsing and integrating
module, the array spatial effect smoothing and visualization module, the probe
level multi-array normalization module, the gene expression intensity
summarization module and the gene expression status inference module.
AVAILABILITY: http://plantgenomics.biology.yale.edu/nmpp
PMID- 17038342
TI - Maximum likelihood inference of imprinting and allele-specific expression from
EST data.
AB - MOTIVATION: In a diploid organism the proportion of transcripts that are produced
from the two parental alleles can differ substantially due, for example to
epigenetic modification that causes complete or partial silencing of one parental
allele or to cis acting polymorphisms that affect transcriptional regulation.
Counts of SNP alleles derived from EST sequences have been used to identify both
novel candidates for genomic imprinting as well as examples of genes with allelic
differences in expression. RESULTS: We have developed a set of statistical models
in a maximum likelihood framework that can make highly efficient use of public
transcript data to identify genes with unequal representation of alternative
alleles in cDNA libraries. We modelled both imprinting and allele-specific
expression and applied the models to a large dataset of SNPs mapped to EST
sequences. Using simulations, matched closely to real data, we demonstrate
significantly improved performance over existing methods that have been applied
to the same data. We further validated the power of this approach to detect
imprinting using a set of known imprinted genes and inferred a set of candidate
imprinted genes, several of which are in close proximity to known imprinted
genes. We report evidence that there are undiscovered imprinted genes in known
imprinted regions. Overall, more than half of the genes for which the most data
are available show some evidence of allele-specific expression. AVAILABILITY:
Software is available from the authors on request.
PMID- 17038343
TI - THOR: targeted high-throughput ortholog reconstructor.
AB - Low-coverage genomes (LCGs) are becoming an increasingly important source of data
for phylogenetic studies. However, assembly of these genomes is time consuming,
difficult and lags behind sequence generation. THOR is a fast, stringent
application for targeted reconstruction of sequence orthologs in unassembled
LCGs. Using a 4x coverage set of mouse whole-genome sequence reads, THOR could
partially or completely reconstruct 416/1000 human promoter ortholog regions in
approximately 7.3 min/promoter. THOR's reconstruction rate improves markedly with
both higher-coverage, and less divergent target species.
PMID- 17038344
TI - Parameter estimation using Simulated Annealing for S-system models of biochemical
networks.
AB - MOTIVATION: High-throughput technologies now allow the acquisition of biological
data, such as comprehensive biochemical time-courses at unprecedented rates.
These temporal profiles carry topological and kinetic information regarding the
biochemical network from which they were drawn. Retrieving this information will
require systematic application of both experimental and computational methods.
RESULTS: S-systems are non-linear mathematical approximative models based on the
power-law formalism. They provide a general framework for the simulation of
integrated biological systems exhibiting complex dynamics, such as genetic
circuits, signal transduction and metabolic networks. We describe how the
heuristic optimization technique simulated annealing (SA) can be effectively used
for estimating the parameters of S-systems from time-course biochemical data. We
demonstrate our methods using three artificial networks designed to simulate
different network topologies and behavior. We then end with an application to a
real biochemical network by creating a working model for the cadBA system in
Escherichia coli. AVAILABILITY: The source code written in C++ is available at
http://www.engg.upd.edu.ph/~naval/bioinformcode.html. All the necessary programs
including the required compiler are described in a document archived with the
source code. SUPPLEMENTARY INFORMATION: Supplementary material is available at
Bioinformatics online.
PMID- 17038345
TI - Repseek, a tool to retrieve approximate repeats from large DNA sequences.
AB - Chromosomes or other long DNA sequences contain many highly similar repeated sub
sequences. While there are efficient methods for detecting strict repeats or
detecting already characterized repeats, there is no software available for
detecting approximate repeats in large DNA sequences allowing for weighted
substitutions and indels in a coherent statistical framework. Here, we present an
implementation of a two-steps method (seed detection followed by their extension)
that detects those approximate repeats. Our method is computationally efficient
enough to handle large sequences and is flexible enough to account for
influencing factors, such as sequence-composition biases both at the seed
detection and alignment levels. AVAILABILITY:
http://wwwabi.snv.jussieu.fr/public/RepSeek/
PMID- 17038346
TI - Supporting the SBML layout extension.
AB - MOTIVATION: Researchers studying large or complex biochemical networks would
benefit from the ability to automatically create lucid visualizations and store
them in a portable and widely accepted format. SUMMARY: Two modules,
SBMLSupportLayout and SBWAutoLayout, support reading, creating, manipulating and
writing layout information for biochemical models. SBMLSupportLayout can read,
update, add and render model layout information. SBWAutoLayout can automatically
layout models, graphically manipulate model layout and generate layout
information for models without layout information. AVAILABILITY:
SBMLSupportLayout and SBWAutoLayout are distributed with the Systems Biology
Workbench (SBW), which can be downloaded from http://www.sys-bio.org.
Additionally, their visualization and layout capabilities are available online at
http://www.sys-bio.org/Layout. Both modules run on Win32, Linux and the Mac OS X
version is forthcoming.
PMID- 17038347
TI - Cell++--simulating biochemical pathways.
AB - MOTIVATION: With the generation of a wealth of information, detailing cellular
components, their functions and interactions, there is a growing need for the
development of new computational tools capable of interpreting these data within
spatial and dynamic contexts. Here, we introduce Cell++, a novel stochastic
simulation environment with the capacity to study a wide variety of biochemical
processes within a spatial context. RESULTS: Focusing on three case studies, we
highlight the potential impact of spatial organization in the evolution and
engineering of signaling and metabolic pathways. In addition to altering
signaling and metabolic efficiency, simulations also demonstrated features
consistent with the phenomenon of metabolic channeling. AVAILABILITY: Cell++ is
licensed under the GNU general public license (GPL) and has been successfully
implemented under Linux and IRIX operating systems. Source code together with a
simple tutorial is available at http://www.compsysbio.org/CellSim/.
PMID- 17038348
TI - Genetic characterization of the dihydrofolate reductase gene of Pneumocystis
jirovecii isolates from Portugal.
AB - OBJECTIVES: The aim of the present study was to evaluate the genetic variation of
Pneumocystis jirovecii dihydrofolate reductase (DHFR) gene in an
immunocompromised Portuguese population and to investigate the possible
association between DHFR genotypes and P. jirovecii pneumonia (PcP) prophylaxis
with co-trimoxazole. METHODS: One hundred and thirty-eight P. jirovecii isolates
were submitted to DHFR genetic characterization by PCR and sequencing. RESULTS:
In the studied population, 72.7% of the patients presented sequences identical to
the wild-type sequence of the P. jirovecii DHFR gene and 27.3% presented point
substitutions. A total of nine substitution sites were identified; four
synonymous substitutions at nucleotide positions 201, 272, 312 and 381 were
detected in 31 patients. Five non-synonymous substitutions were observed, leading
to the DHFR mutations Leu-13-->Ser, Asn-23-->Ser, Ser-31-->Phe, Met-52-->Leu and
Ala-67-->Val. With the exception of the polymorphism at position 312 and the
mutation at codon 52, all polymorphisms were reported in this study for the first
time. CONCLUSIONS: Our results suggest that DHFR gene polymorphisms are frequent
in the Portuguese immunocompromised population but do not seem to be associated
with PcP prophylaxis failure (P = 0.748 and P = 0.730).
PMID- 17038349
TI - Is inducibility of atrial fibrillation after radio frequency ablation really a
relevant prognostic factor?
AB - AIMS: The study was intended to assess the prognostic value of inducibility of
atrial fibrillation (AF) after radio frequency ablation. METHODS AND RESULTS: Two
hundred and thirty four patients with drug-resistant paroxysmal (n=165) or
persistent AF (n=69) underwent either Lasso-guided segmental pulmonary vein
isolation (n=83) or CARTO-guided left atrial circumferential ablation (n=151).
After ablation, two attempts to induce AF (>1 min) by decremental coronary sinus
stimulation were performed. Patients were followed for at least 6 months (median:
12.7 months). At 6 months of follow-up, 67% of patients with paroxysmal and 48%
of patients with persistent AF were AF-free. Inducibility of AF was a significant
predictor of AF recurrence in univariate [hazard ratio (HR)=2.32, P<0.001] and
multivariable (HR=2.19, P<0.001) Cox regression analyses. The prognostic value of
inducibility was present in both patients with paroxysmal (HR=2.38, P=0.001) and
persistent AF (HR=1.91, P=0.034) and did not significantly differ between both
ablation techniques. The sensitivity, specificity, positive, and negative
predictive values of the AF induction test to predict the 6-month ablation
outcome were 46.7, 75, 53.8, and 69.2%, respectively. CONCLUSION: Inducibility of
AF after ablation is a significant predictor of recurrent AF. However, owing to
the low diagnostic accuracy of the AF induction test, non-inducibility does not
qualify as reliable procedural endpoint.
PMID- 17038350
TI - Devices in heart failure: building up the evidence.
PMID- 17038351
TI - Coronary Buerger's disease with a peripheral arterial aneurysm.
PMID- 17038352
TI - Enhanced Fc-dependent cellular cytotoxicity of Fc fusion proteins derived from
TNF receptor II and LFA-3 by fucose removal from Asn-linked oligosaccharides.
AB - Fucose removal from complex-type oligosaccharide of human IgGs results in a major
enhancement of Fc-dependent cellular cytotoxicity. The aim of this study was to
determine the effect of fucose removal on the effector function of another class
of clinically important molecules that can effect cellular cytotoxicity, Fc
fusion proteins. The receptors chosen for study were TNF receptor II and LFA-3,
both of which have therapeutic significance. The fucosylated versions of these
fusion proteins were produced in unmodified CHO cells, whereas the nonfucosylated
counterparts were produced in CHO cells with alpha-1,6-fucosyltransferase, an
enzyme required for fucosylation, knocked-out. Whilst binding activity of TNFRII
Fc and LFA-3-Fc were unchanged by fucose-removal, nonfucosylated Fc fusion
proteins exhibited significantly higher Fc receptor gammaIIIa-binding and
increased Fc-mediated cytotoxicity on target cells compared to fucosylated
counterparts. Notably, in case of TNFRII-Fc, only the nonfucosylated protein
exhibited potent Fc dependent cytotoxicity to transmembrane TNF-alpha expressing
cells. These results prove that enhancement of Fc dependent cellular cytotoxicity
by fucose-removal is effective in not only whole IgG but also Fc fusion proteins,
and thus widens the potential of Fc-fusion proteins as therapeutic candidates.
PMID- 17038403
TI - Improved characterisation of the HPA PADC neutron personal dosemeter.
AB - The fast neutron energy dependence of response of the HPA PADC neutron personal
dosemeter has been measured from 144 keV to 19 MeV using monoenergetic neutron
fields. Below 144 keV the relative energy and angle dependence of response have
been determined using MCNP-4C2. New data from the SIGMA field at Cadarache,
France, have been used to determine the appropriate scaling factor for the
calculated response to thermal and intermediate energy neutrons. These newly
determined response characteristics of the dosemeter are discussed with respect
to its performance in the EVIDOS workplace field irradiations.
PMID- 17038404
TI - Treating voxel geometries in radiation protection dosimetry with a patched
version of the Monte Carlo codes MCNP and MCNPX.
AB - The question of Monte Carlo simulation of radiation transport in voxel geometries
is addressed. Patched versions of the MCNP and MCNPX codes are developed aimed at
transporting radiation both in the standard geometry mode and in the voxel
geometry treatment. The patched code reads an unformatted FORTRAN file derived
from DICOM format data and uses special subroutines to handle voxel-to-voxel
radiation transport. The various phases of the development of the methodology are
discussed together with the new input options. Examples are given of employment
of the code in internal and external dosimetry and comparisons with results from
other groups are reported.
PMID- 17038405
TI - Identification of static exposure of standard dosimetric badge with
thermoluminescent detectors.
AB - There are three main methods used in individual monitoring: radiographic films,
thermoluminescence (TL) and optically stimulated luminescence (OSL).
Distinguishing between static (e.g. by leaving it accidentally or purposely in
the radiation field) and dynamic exposures can be almost routinely performed for
radiographic and OSL methods but is still unsolved for TL detectors. The main aim
of this work is to develop a method for identifying static exposures of standard
TL detectors at doses which are typical of radiation protection. For this
purpose, a new TLD reader equipped with a CCD camera was developed to measure the
two-dimensional signal map and not only the total light emitted (as is performed
with standard photomultiplier-based TL readers). Standard MCP-N (LiF:Mg,Cu,P) TL
pellets of 4.5 mm diameter and 0.9 mm thickness were installed in the standard
Rados TL personal badges with special, non-uniform filters and exposed statically
to 33 keV X-ray beams at three angles: 0 degrees, 30 degrees and 60 degrees. The
detectors were readout in the CCD camera reader and 2-D images were collected.
The analysis of these CCD images allows the identification of the static exposure
cases and partly the angle of incidence at a dose level of 20 mSv.
PMID- 17038406
TI - Progress report of the CR-39 neutron personal monitoring service at PSI.
AB - At the Paul Scherrer Institute a personal neutron dosimetry system based on
chemically etched CR-39 detectors and automatic track counting is in routine use
since the beginning of 1998. The quality of the CR-39 detectors has always been a
crucial aspect to maintain a trustable personal neutron dosimetry system. This
paper summarises the 7 y experience in routine use. The effect of detector
material defects which could lead to false positive neutron doses is described.
The potentiality of improving the background statistics by extending the pre-etch
time is investigated and involves as a drawback a quite lower sensitivity to
thermal neutrons. Furthermore, the impact of small changes in the production
process of the detectors on the response to fast and thermal neutrons is shown.
For the personal dosimetry at CERN, a new dosimetry concept was launched by
combining a CR-39 neutron dosemeter with a Direct-Ion Storage (DIS) dosemeter for
photon and beta radiation. The usage period of the CR-39 dosemeters is prolonged
now from 3 months up to 12 months. In this context, the long-term behaviour over
1 y of the background track density and the response to Am-Be are described.
PMID- 17038407
TI - Practical assessment of the display performance of radiology workstations.
AB - The performance of 14 primary clinical display monitor workstations in use in the
Radiology Department of a large acute NHS Trust was assessed using the methods
and guidelines described by the American Association of Physicists in Medicine
Task Group 18. Tests undertaken included the measurement of ambient light,
display uniformity, luminance ratio, luminance response, maximum luminance and
spatial resolution. Four display monitors failed to meet at least one of the
test's guideline tolerances. In addition a number of display monitors were found
to be operating at settings that might reduce their useful life span. These
devices were either replaced or recalibrated by the installers, or were subject
to local adjustment to ensure applicable standards were met. Consequently the
study suggests that quality assurance testing of display monitors used for image
reporting is necessary and valuable to ensure that images are viewed at an
appropriate standard.
PMID- 17038408
TI - An efficient method for calculating kinetic parameters in a dual-input single
compartment model.
AB - Quantitative measurement of hepatic perfusion has the potential to provide
important information in the assessment and management of various liver diseases.
The utility of hepatic perfusion characterization relies on the resolution of
each component of its dual blood supply, i.e. the hepatic artery and portal vein.
In this study, a linear equation was derived by integrating the differential
equation describing the kinetic behaviour of contrast agent (CA) in a dual-input
single-compartment model, from which the kinetic parameters can be easily
obtained using the linear least-squares method. The usefulness of this method was
investigated using computer simulations, in comparison with the non-linear least
squares (NLSQ) method. This method calculated the kinetic parameters faster than
the NLSQ method by a factor of approximately 10, with almost the same accuracy as
the NLSQ method. This method will be useful for analysing the kinetic behaviour
of CA in the unique liver environment, especially by generating the functional
images of kinetic parameters.
PMID- 17038409
TI - Usefulness of saline pushing in reduction of contrast material dose in abdominal
CT: evaluation of time-density curve for the aorta, portal vein and liver.
AB - The effects of saline pushing after contrast material injection were investigated
as well as the possibility for this technique to reduce contrast material doses
in liver CT examinations. 52 patients were divided randomly into three groups:
100 ml of contrast material (300 mg I ml(-1)) only (A; n = 19), 100 ml of
contrast material pushed with 50 ml of saline solution (B; n = 17), and 85 ml of
contrast material pushed with 50 ml of saline solution (C; n = 16). Single-level
images were obtained at the level of the main portal vein after the initiation of
contrast material injection. There were no significant differences in the mean
peak enhancement values (PE) and the mean time to peak enhancement values (TPE)
of the aorta between the three groups. The mean PE of the portal vein in group B
increased 21 HU over that in group A (p<0.05), and there was no significant
difference between groups A and C. The mean PE of the liver in group B increased
7 HU over that in group A (p<0.05), and there was no significant difference
between groups A and C. The mean TPE of the portal vein was shorter by 4 s
(p<0.05), and that of the liver was shorter by 5 s (p<0.05) in group C compared
with those in group A. In conclusion, saline pushing increases the enhancement
values of the portal vein and liver, and allows a contrast material dose
reduction of 15 ml without decreasing hepatic and vascular enhancement at
adequate scan timing.
PMID- 17038410
TI - 16-slice CT: achievable effective doses of common protocols in comparison with
recent CT dose surveys.
AB - The aim of the study was to investigate achievable dose levels in 16-slice CT by
evaluating CT dose indices (CTDI) and effective doses of dose-optimized protocols
compared with 4-slice dose surveys. Normalized CTDI free in air and in 16 cm and
32 cm diameter phantoms were measured on four different 16-slice CT scanners in
the Netherlands. All collimation and tube potential settings were analysed.
Volume CTDI was calculated for adult protocols for brain, chest, pulmonary
angiography (CTPA), abdomen and biphasic liver CT. Effective doses were
calculated first using volume CTDI with conversion factors and second from
CTDIair values using the ImPACT dose calculator. Average results of the 16-slice
scanners were correlated to results of dose surveys with predominantly 4-slice
scanners. Statistical analysis was done with Student t-tests with a Bonferroni
correction; therefore p < 0.017 was significant. The results of CTDIair and
weighted CTDI were documented for all scanners. Effective doses averaged over
four scanners for brain, chest, CTPA, abdomen and biphasic liver protocols were
1.9+/-0.4, 3.8+/-0.4, 3.0+/-0.2, 7.2+/-0.9 and 10.2+/-1.3 mSv, respectively.
Compared with dose surveys achievable effective doses were equal (p = 0.069) to
significantly lower (p < 0.017) for chest and abdomen protocols. For 16-slice
spiral brain CT there was a trend of equal doses compared with sequential brain
CT in the dose surveys. Thus, with dose-optimized protocols 16-slice CT can
achieve equal to lower effective doses in examinations of the chest and abdomen
compared with 4-slice CT, while doses can remain stable in the brain.
PMID- 17038411
TI - Metastatic carcinoma of the breast: the appearances of metastatic spread to the
abdomen and pelvis as demonstrated by CT.
AB - This review illustrates some CT appearances of metastatic breast cancer in the
subdiaphragmatic abdomen and pelvis. Such manifestations are not uncommon in
advanced disease and familiarity will enable confident diagnosis in patients at
risk for metastatic disease.
PMID- 17038412
TI - Combined therapy of transcatheter arterial chemoembolisation and three
dimensional conformal radiotherapy for hepatocellular carcinoma.
AB - To evaluate the toxicity and efficacy of combined therapy of three-dimensional
conformal radiotherapy (3DCRT) and transcatheter arterial chemoembolisation
(TACE) for hepatocellular carcinoma (HCC). 50 HCC patients treated by combined
TACE and 3DCRT were selected from a patient database. Sequence of treatments was
that TACE was performed first, followed by 3DCRT with an interval of about 4
weeks between. TACE was administered by 5-Fu 500-600 mg m(-2), cis-platinum 30-40
mg m(-2), epi-adriamycin 40-60 mg m(-2) mixed with iodized oil and Gelfoam
embolisation. A median of two courses of TACE was given. 3DCRT was delivered by 4
6 coplanar or non-coplanar fields. The mean tumour dose was 43.0+/-6.3 Gy by
conventional fractionation (2 Gy per fraction, five fractions a week), and mean
dose to normal liver, 19.1+/-6.3 Gy. Acute hepatic toxicities were notable in
five patients (10%) with Common Toxicity Criteria (CTC) grade 1 in two cases and
grade 3 in three patients, but all recovered eventually. Two patients developed
radiation-induced liver disease (RILD) and died soon after the onset of RILD.
Four patients had Radiation Therapy Oncology Group (RTOG) grade 1 acute
gastrointestinal complication and one patient had acute gastrointestinal
bleeding. Five patients experienced RTOG Grade 1 leukopenia and Grade 2 in five
cases. Nine patients achieved have partial response, and 37 patients were in
stable disease. Four patients were observed to have progressive disease. The
overall survival rates at 1 year, 2 years and 3 years were 60%, 38% and 28%,
respectively, with a median survival period of 17 months. Irradiation dose, T
stage and hepatic cirrhosis were identified as independent predictors for overall
survival by Cox proportional regression analysis. The 1 year, 2 years and 3 years
local progression-free rates were 74%, 57% and 38%, and the 1 year, 2 years and 3
years distant metastasis rates were 15%, 21% and 40%, respectively. The combined
modality of TACE and 3DCRT was tolerable for the majority of HCC patients,
resulted in good outcome and warrants for further prospective trial.
PMID- 17038413
TI - Risk factors for induction of breast cancer by X-rays and their implications for
breast screening.
AB - In order to discuss the balance of benefit and radiation risk in a breast
screening programme, it is necessary to have numerical values for the probability
of breast cancer induction by X-rays, stratified by age. Various sets of such
values have been used hitherto, mainly in relation to breast screening in the UK,
both within the NHS Screening Programme and more generally for younger age
groups. Further sets have recently been reported. These different sets of values
are described and discussed, together with the effects of using additive or
relative risk models, and the effect of using a dose and dose rate modifying
factor (DDREF). Possible new radiation risk factors for breast cancer induction
by X-rays, drawn from these sets, are identified. These are used to calculate
fresh values of cancer detection/induction ratios, as an index of benefit/risk,
for screening age women and for younger women with and without a family history
of breast cancer.
PMID- 17038414
TI - Temperament and pain reactivity predict health behavior seven years later.
AB - OBJECTIVE: Minor illnesses and major diseases are affected by individual,
environmental, and social factors. We sought to determine if children's
temperament and pain reactivity (individual response styles) measured in
kindergarten are related to future health behavior. METHODS: Seven-year follow-up
measures of health behavior were gathered in 42 children (mean age M = 11 years)
who participated in a previous study of pain reactivity and somatization. Current
health behavior was compared with children's pain reactivity and temperament
measured in kindergarten. RESULTS: Pain reactivity in kindergarten was associated
with children's self-reports of somatization 7 years later, independent of their
temperament. Temperament was related to children's self-reports of somatization
and to maternal reports of health care utilization and psychosocial health
status. CONCLUSIONS: Early response styles (i.e., heightened pain reactivity and
difficulty adjusting) may indicate risk for increased health care utilization and
poorer health and well-being later in childhood.
PMID- 17038415
TI - Jellyfish responsible for Irukandji syndrome.
PMID- 17038417
TI - Jellyfish responsible for Irukandji syndrome.
PMID- 17038418
TI - Cardiovascular disease risk factor knowledge in young adults and 10-year change
in risk factors: the Coronary Artery Risk Development in Young Adults (CARDIA)
Study.
AB - This study's objective was assessment of cardiovascular disease (CVD) risk factor
knowledge in young adults, its association with 10-year changes in risk factor
levels, and variables related to risk factor knowledge. A total of 4,193 healthy
persons (55% female, 48% Black; mean age=30 years) from four urban US communities
were queried about risk factor knowledge in 1990-1991 and were reexamined in 2000
2001. Of six risk factors considered (hypertension, hyperlipidemia, smoking,
overweight, sedentary lifestyle, and unhealthy diet), participants mentioned a
mean of two; more than 65% were not aware of any risk factors, and less than 35%
recognized being overweight as a risk factor. After adjustment, variables
associated with mentioning more than two CVD risk factors versus one or fewer
were Black race (OR=0.52, 95% confidence interval (CI): 0.44, 0.61), having a
high school education or less (OR=0.88, 95% CI: 0.80, 0.95), having one or two
(vs. zero) risk factors (OR=1.27, 95% CI: 1.05, 1.53), and having three or more
(vs. zero) risk factors (OR=1.79, 95% CI: 1.35, 2.38). More knowledge was
marginally associated with less increase in body mass index 10 years later
(p=0.06) but was unrelated to other risk factor changes. Knowledge of CVD risk
factors was very low in these young adults but increased with the presence of
risk factors. Knowledge alone did not predict 10-year changes in risk factors.
PMID- 17038419
TI - The use of in vitro peptide binding profiles and in silico ligand-receptor
interaction profiles to describe ligand-induced conformations of the retinoid X
receptor alpha ligand-binding domain.
AB - It is hypothesized that different ligand-induced conformational changes can
explain the different interactions of nuclear receptors with regulatory proteins,
resulting in specific biological activities. Understanding the mechanism of how
ligands regulate cofactor interaction facilitates drug design. To investigate
these ligand-induced conformational changes at the surface of proteins, we
performed a time-resolved fluorescence resonance energy transfer assay with 52
different cofactor peptides measuring the ligand-induced cofactor recruitment to
the retinoid X receptor-alpha (RXRalpha) in the presence of 11 compounds.
Simultaneously we analyzed the binding modes of these compounds by molecular
docking. An automated method converted the complex three-dimensional data of
ligand-protein interactions into two-dimensional fingerprints, the so-called
ligand-receptor interaction profiles. For a subset of compounds the
conformational changes at the surface, as measured by peptide recruitment,
correlate well with the calculated binding modes, suggesting that clustering of
ligand-receptor interaction profiles is a very useful tool to discriminate
compounds that may induce different conformations and possibly different effects
in a cellular environment. In addition, we successfully combined ligand-receptor
interaction profiles and peptide recruitment data to reveal structural elements
that are possibly involved in the ligand-induced conformations. Interestingly, we
could predict a possible binding mode of LG100754, a homodimer antagonist that
showed no effect on peptide recruitment. Finally, the extensive analysis of the
peptide recruitment profiles provided novel insight in the potential cellular
effect of the compound; for the first time, we showed that in addition to the
induction of coactivator peptide binding, all well-known RXRalpha agonists also
induce binding of corepressor peptides to RXRalpha.
PMID- 17038420
TI - Perceptions of Maori deaf identity in New Zealand.
AB - Following the reframing of "Deaf" as a cultural and linguistic identity, ethnic
minority members of Deaf communities are increasingly exploring their plural
identities in relation to Deaf and hearing communities of affiliation. This
article examines Maori Deaf people's perceptions of identity, during a coinciding
period of Tino Rangatiratanga (Maori cultural and political self-determination
and empowerment)1 and the emergence of Deaf empowerment. Interviews with 10 Maori
Deaf participants reveal experiences of enculturation into Maori and Deaf
communities and how they negotiate identity in these contexts. Consistent with
the model of contextual identity in Deaf minority individuals of Foster and
Kinuthia (2003), participants expressed fluid identities, in which Maori and Deaf
aspects are both central but foregrounded differently in their interactions with
hearing Maori, Deaf Maori, and the wider Deaf community. This New Zealand case
study illustrates how changing sociopolitical conditions affect Deaf minority
individuals' opportunity to achieve and express identification with both Deaf
world and family heritage cultures.
PMID- 17038421
TI - Biogeographic evidence for selection on mitochondrial DNA in North Pacific
walleye pollock Theragra chalcogramma.
AB - Three major mitochondrial DNA (mtDNA) haplogroups were identified in 5 data sets
for North Pacific and Bering Sea walleye pollock. The common haplogroup A showed
mirror-image clines on both sides of the North Pacific with high frequencies in
southern areas (P(A) > 0.84) and low frequencies in the Bering Sea (P(A) < 0.36).
Two additional haplogroups showed complimentary, but weaker, clines in the
opposite direction. These clines are unlikely to have arisen by chance during
postglacial colonizations of coastal waters in the North Pacific and Bering Sea,
and they do not appear to reflect isolation by distance. Contrary to these
trends, pollock at the western end of the Aleutian Island Archipelago were
genetically more similar to Asian than to North American pollock, a pattern
likely reflecting postglacial colonization. Haplogroup F(ST) values for a given
haplotype diversity were significantly larger than expected under the island
model of migration and random drift, a result implicating natural selection.
Frequencies of haplogroup A were highly correlated with sea surface temperature
(r > 0.91), whereas frequencies of groups B and C showed negative correlations
with temperature. Selection may be operating directly on mtDNA variability or may
be mediated through cytonuclear interactions. This biogeographic evidence adds to
a growing body of literature indicating that selection may play a greater role in
sculpting mtDNA variability than previously thought.
PMID- 17038422
TI - TRPV1 is a novel target for omega-3 polyunsaturated fatty acids.
AB - Omega-3 (n-3) fatty acids are essential for proper neuronal function, and they
possess prominent analgesic properties, yet their underlying signalling
mechanisms are unclear. Here we show that n-3 fatty acids interact directly with
TRPV1, an ion channel expressed in nociceptive neurones and brain. These fatty
acids activate TRPV1 in a phosphorylation-dependent manner, enhance responses to
extracellular protons, and displace binding of the ultrapotent TRPV1 ligand
[3H]resiniferatoxin. In contrast to their agonistic properties, n-3 fatty acids
competitively inhibit the responses of vanilloid agonists. These actions occur in
mammalian cells in the physiological concentration range of 1-10 mum.
Significantly, docosahexaenoic acid exhibits the greatest efficacy as an agonist,
whereas eicosapentaenoic acid and linolenic acid are markedly more effective
inhibitors. Similarly, eicosapentaenoic acid but not docosahexaenoic acid
profoundly reduces capsaicin-evoked pain-related behaviour in mice. These effects
are independent of alterations in membrane elasticity because the micelle-forming
detergent Triton X-100 only minimally affects TRPV1 properties. Thus, n-3 fatty
acids differentially regulate TRPV1 and this form of signalling may contribute to
their biological effects. Further, these results suggest that dietary
supplementation with selective n-3 fatty acids would be most beneficial for the
treatment of pain.
PMID- 17038423
TI - Postnatal changes in ventilation during normoxia and acute hypoxia in the rat:
implication for a sensitive period.
AB - Previously, we found heightened expression of inhibitory neurochemicals and
depressed expression of excitatory neurochemicals with a sudden drop in metabolic
activity around postnatal day (P) 12 in rat brainstem respiratory nuclei,
suggesting that this period is a critical window during which respiratory control
or regulation may be distinctly different. To test this hypothesis, the hypoxic
ventilatory responses (HVR) to 10% oxygen were tested in rats every day from P0
to P21. Our data indicate that (1) during normoxia (N), breathing frequency (f)
increased with age, peaking at P13, followed by a gradual decline, whereas both
tidal volume (V(T)) and minute ventilation (.V(E) ) significantly increased in
the second postnatal week, followed by a progressive increase in V(T) and a
relative plateau in .V(E); (2) during 5 min of hypoxia (H), .V(E) exhibited a
biphasic response from P3 onward. Significantly, the ratio of .V(E)(H) to
.V(E)(N) was generally > 1 during development, except for P13-16, when it was < 1
after the first 1-2 min, with the lowest value at P13; (3) the H : N ratio for f,
V(T) and .V(E) during the first 30 s and the last minute of hypoxia all showed a
distinct dip at P13, after which the V(T) and .V(E) values rose again, while the
f values declined through P21; and (4) the H : N ratios for f, V(T) and .V(E)
averaged over 5 min of hypoxia all exhibited a sudden fall at P13. The f ratio
remained low thereafter, while those for V(T) and .V(E) increased again with age
until P21. Thus, hypoxic ventilatory response is influenced by both f and V(T)
before P13, but predominantly by V(T) after P13. The striking changes in normoxic
ventilation as well as HVR at or around P13, together with our previous
neurochemical and metabolic data, strongly suggests that the end of the second
postnatal week is a critical period of development for brainstem respiratory
nuclei in the rat.
PMID- 17038424
TI - The oestrogen receptor beta contributes to sex related differences in endothelial
function of murine small arteries via EDHF.
AB - Sex related differences in cardiovascular function have been reported in
oestrogen receptor beta knockout (ERbetaKO) mice. In this study we examined the
role of endothelium-derived hyperpolarizing factor (EDHF) in differences in small
artery endothelial function between ERbetaKO and wild-type (WT) mice. Small
femoral arteries were isolated from ERbetaKO and WT mice and mounted on a wire
myograph. Concentration-response curves to ACh were compared before and after
incubation with inhibitors of nitric oxide (NO) and prostacyclin (PGI2)
synthesis. Comparison of the expression of the principal vascular connexins
(Cx37, 40 and 43), implicated in EDHF-mediated dilatation were undertaken by
immunohistochemistry. Vascular ultrastructure was studied by transmission and
scanning electron microscopy. ACh-induced relaxation of arteries (< 200 microm
internal diameter) was greater in WT females versus males and was attributable to
a greater EDHF component of relaxation. This sex difference was absent in
ERbetaKO mice. Arteries from ERbetaKO males (but not females) were more sensitive
to ACh compared to WT. The pharmacological evidence and morphological
prerequisite for involvement of gap junctions in EDHF-mediated responses was
confirmed in male arteries. The absence of ERbeta had no influence on expression
of main Cx subtypes within vascular wall or on ultrastructure and morphology of
the endothelium. The data suggest that in WT male mice, ERbeta reduces EDHF
mediated relaxation through gap junction communication.
PMID- 17038425
TI - Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal
muscle.
AB - 5'AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolism
and is regulated in muscle during exercise. We have previously established that
only three of 12 possible AMPK alpha/beta/gamma-heterotrimers are present in
human skeletal muscle. Previous studies describe discrepancies between total AMPK
activity and regulation of its target acetyl-CoA-carboxylase (ACC)beta. Also,
exercise training decreases expression of the regulatory gamma3 AMPK subunit and
attenuates alpha2 AMPK activity during exercise. We hypothesize that these
observations reflect a differential regulation of the AMPK heterotrimers. We
provide evidence here that only the alpha2/beta2/gamma3 subunit is phosphorylated
and activated during high-intensity exercise in vivo. The activity associated
with the remaining two AMPK heterotrimers, alpha1/beta2/gamma1 and
alpha2/beta2/gamma1, is either unchanged (20 min, 80% maximal oxygen uptake ) or
decreased (30 or 120 s sprint-exercise). The differential activity of the
heterotrimers leads to a total alpha-AMPK activity, that is decreased (30 s
trial), unchanged (120 s trial) and increased (20 min trial). AMPK activity
associated with the alpha2/beta2/gamma3 heterotrimer was strongly correlated to
gamma3-associated alpha-Thr-172 AMPK phosphorylation (r(2) = 0.84, P < 0.001) and
to ACCbeta Ser-221 phosphorylation (r(2) = 0.65, P < 0.001). These data single
out the alpha2/beta2/gamma3 heterotrimer as an important actor in exercise
regulated AMPK signalling in human skeletal muscle, probably mediating
phosphorylation of ACCbeta.
PMID- 17038426
TI - Histaminergic and glycinergic modulation of GABA release in the vestibular nuclei
of normal and labyrinthectomised rats.
AB - Vestibular compensation (the behavioural recovery that follows unilateral
vestibular de-afferentation), is facilitated by histamine, and is associated with
increased central histamine release and alterations in histamine H(3) receptor
expression in the vestibular nuclei. However, little is known of the effects of
histamine on neurotransmission in the vestibular nuclei, and the mechanisms by
which histamine may influence compensation are unclear. Here we examined the
modulatory effects of histaminergic agents on the release of amino acid
neurotransmitters in slices of the medial vestibular nucleus (MVN) prepared from
normal and labyrinthectomised rats. The release of GABA, but not glutamate,
glycine or aspartate, was robustly and reproducibly evoked by a high-K(+)
stimulus applied to normal MVN slices. Histamine inhibited the evoked release of
GABA, both through a direct action on presynaptic H(3) receptors (presumably
located on GABAergic terminals), and through a novel, indirect pathway that
involved the increased release of glycine by activation of postsynaptic H(1)/H(2)
receptors (presumably on glycinergic neurons). After unilateral labyrinthectomy
(UL), the direct H(3) receptor-mediated inhibition of GABA release was profoundly
downregulated in both ipsi-lesional and contra-lesional MVNs. This effect
appeared within 25 h post-UL and persisted for at least 3 weeks post-UL. In
addition, at 25 h post-UL the indirect glycinergic pathway caused a marked
suppression of GABA release in the contra-lesional but not ipsi-lesional MVN,
which was overcome by strychnine. Stimulation of histamine H(3) receptors at 25 h
post-UL restored contra-lesional GABA release to normal, suggesting that acutely
after UL H(3) receptors may strongly modulate glycinergic and GABAergic
neurotransmission in the MVN. These findings are the first to demonstrate the
modulatory actions of the histaminergic system on neurotransmission in the
vestibular nuclei, and the changes that occur during vestibular system
plasticity. During vestibular compensation, histaminergic modulation of glycine
and GABA release may contribute to the rebalancing of neural activity in the
vestibular nuclei of the lesioned and intact sides.
PMID- 17038427
TI - Genetically encoded Ca2+ indicators: using genetics and molecular design to
understand complex physiology.
AB - This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on
the use of these novel molecules in the context of understanding complex cell
signalling in mammals, in vivo. The review focuses on the advantages and
limitations of specific GECI design strategies and the results of experiments in
which these molecules have been expressed in transgenic mice, concentrating
particularly on recent experiments from our laboratory in which physiological
signalling could be monitored in vivo. Finally, newer strategies for effective
genetic specification of GECIs are briefly reviewed.
PMID- 17038428
TI - Reduced nicotinic receptor function in sympathetic ganglia is responsible for the
hypothermia in the acetylcholinesterase knockout mouse.
AB - Cholinergic signalling in the sympathetic ganglia (SG) contributes to non
shivering thermogenesis by relaying the activation signal from the brain to SG
neurons which activate many peripheral tissues to produce heat. Paradoxically,
acetylcholinesterase (AChE) inhibitors, which should enhance cholinergic
signalling, induce hypothermia. To understand the mechanism of how cholinergic
signalling in the SG controls thermoregulation, we analysed infant AChE knockout
mice, which are known to show hypothermia by postnatal day 15. Nicotinic receptor
currents were reduced in acutely dissociated SG neurons of the AChE-deficient
mice by over 40% compared with wild-type mice. When wild-type neurons were
treated for 1 h with either oxotremorine-M, a muscarinic agonist, or nicotine,
the amplitude of nicotinic receptor currents was also decreased by 40%. The
hypothermia in AChE mutant mice was fully rescued by a peripheral injection of
both ivermectin, which increases nicotinic receptor currents, and methyl
atropine, a muscarinic antagonist. Our results demonstrate that the hypothermia
induced by the lack of AChE activity is primarily caused by a downregulation of
nicotinic receptors via prolonged stimulation of muscarinic and nicotinic
receptors in SG neurons. The stationary noise analysis of the nicotinic receptor
current traces showed that the properties of single-channel activities were not
different between the two genotypes, suggesting that the primary reason for
downregulation of nicotinic receptors is due to a reduction of the receptors on
the surface.
PMID- 17038429
TI - Response characteristics of the pigeon's pretectal neurons to illusory contours
and motion.
AB - Misinterpretations of visual information received by the retina are called visual
illusions, which are known to occur in higher brain areas. However, whether they
would be also processed in lower brain structures remains unknown, and how to
explain the neuronal mechanisms underlying the motion after-effect is intensely
debated. We show by extracellular recording that all motion-sensitive neurons in
the pigeon's pretectum respond similarly to real and illusory contours, and their
preferred directions are identical for both contours in unidirectional cells,
whereas these directions are changed by 90 deg for real versus illusory contours
in bidirectional cells. On the other hand, some pretectal neurons produce
inhibitory (excitatory) after-responses to cessation of prolonged motion in the
preferred (null) directions, whose time course is similar to that of the motion
after-effect reported by humans. Because excitatory and inhibitory receptive
fields of a pretectal cell overlap in visual space and possess opposite
directionalities, after-responses to cessation of prolonged motion in one
direction may create illusory motion in the opposite direction. It appears that
illusory contours and motion could be detected at the earliest stage of central
information processing and processed in bottom-up streams, and that the motion
after-effect may result from functional interactions of excitatory and inhibitory
receptive fields with opposite directionalities.
PMID- 17038430
TI - Protection conferred by myocardial ATP-sensitive K+ channels in pressure overload
induced congestive heart failure revealed in KCNJ11 Kir6.2-null mutant.
AB - Ventricular load can precipitate development of the heart failure syndrome, yet
the molecular components that control the cardiac adaptive response to imposed
demand remain partly understood. Compromised ATP-sensitive K(+) (K(ATP)) channel
function renders the heart vulnerable to stress, implicating this metabolic
sensor in the homeostatic response that would normally prevent progression of
cardiac disease. Here, pressure overload was imposed on the left ventricle by
transverse aortic constriction in the wild-type and in mice lacking sarcolemmal
K(ATP) channels through Kir6.2 pore knockout (Kir6.2-KO). Despite equivalent
haemodynamic loads, within 30 min of aortic constriction, Kir6.2-KO showed an
aberrant prolongation of action potentials with intracellular calcium overload
and ATP depletion, whereas wild-type maintained ionic and energetic handling. On
catheterization, constricted Kir6.2-KO displayed compromised myocardial
performance with elevated left ventricular end-diastolic pressure, not seen in
the wild-type. Glyburide, a K(ATP) channel inhibitor, reproduced the knockout
phenotype in the wild-type, whereas the calcium channel antagonist, verapamil,
prevented abnormal outcome in Kir6.2-KO. Within 48 h following aortic
constriction, fulminant biventricular congestive heart failure, characterized by
exercise intolerance, cardiac contractile dysfunction, hepatopulmonary congestion
and ascites, halved the Kir6.2-KO cohort, while no signs of organ failure or
mortality were seen in wild-type. Surviving Kir6.2-KO developed premature and
exaggerated fibrotic myocardial hypertrophy associated with nuclear up-regulation
of calcium-dependent pro-remodelling MEF2 and NF-AT pathways, precipitating
chamber dilatation within 3 weeks. Thus, K(ATP) channels appear mandatory in
acute and chronic cardiac adaptation to imposed haemodynamic load, protecting
against congestive heart failure and death.
PMID- 17038431
TI - Purinergic 2 receptor blockade prevents the responses of group IV afferents to
post-contraction circulatory occlusion.
AB - ATP, by activating purinergic 2 (P2) receptors on group III and IV afferents, is
thought to evoke the metabolic component of the exercise pressor reflex.
Previously we have shown that injection of PPADS, a P2 receptor antagonist, into
the arterial supply of skeletal muscle of decerebrated cats attenuated the
responses of group III and IV afferents to static contraction while the muscles
were freely perfused. We have now tested the hypothesis that injection of PPADS
(10 mg kg(-1)) attenuated the responses of group III (n = 13) and group IV
afferents (n = 9) to post-contraction circulatory occlusion. In the present
study, we found that PPADS attenuated the group III afferent responses to static
contraction during circulatory occlusion (P < 0.05). Likewise, PPADS abolished
the group IV afferent responses to static contraction during occlusion (P =
0.001). During a 1 minute period of post-contraction circulatory occlusion, four
of the 13 group III afferents and eight of the nine group IV afferents maintained
their increased discharge. A Fischer's exact probability test revealed that more
group IV afferents than group III afferents were stimulated by post-contraction
circulatory occlusion (P < 0.02). In addition, the nine group IV afferents
increased their mean discharge rate over baseline levels during the post
contraction circulatory occlusion period, whereas the 13 group III afferents did
not (P < 0.05). PPADS abolished this post-contraction increase in discharge by
the group IV afferents (P < 0.05). Our findings suggest that P2 receptors on
group IV afferents play a role in evoking the metabolic component of the exercise
pressor reflex.
PMID- 17038432
TI - Mouse models of long QT syndrome.
AB - Congenital long QT syndrome is a rare inherited condition characterized by
prolongation of action potential duration (APD) in cardiac myocytes, prolongation
of the QT interval on the surface electrocardiogram (ECG), and an increased risk
of syncope and sudden death due to ventricular tachyarrhythmias. Mutations of
cardiac ion channel genes that affect repolarization cause the majority of the
congenital cases. Despite detailed characterizations of the mutated ion channels
at the molecular level, a complete understanding of the mechanisms by which
individual mutations may lead to arrhythmias and sudden death requires study of
the intact heart and its modulation by the autonomic nervous system. Here, we
will review studies of molecularly engineered mice with mutations in the genes
(a) known to cause long QT syndrome in humans and (b) specific to cardiac
repolarization in the mouse. Our goal is to provide the reader with a
comprehensive overview of mouse models with long QT syndrome and to emphasize the
advantages and limitations of these models.
PMID- 17038433
TI - Macrophages promote muscle membrane repair and muscle fibre growth and
regeneration during modified muscle loading in mice in vivo.
AB - Muscle injury or modified muscle use can stimulate muscle invasion by leucocytes
that have the potential to increase tissue damage or promote tissue growth and
repair. In the present investigation, we examined the role of macrophages in
muscle injury, repair and regeneration during modified muscle loading. Weight
bearing was removed from the hindlimbs of mice for 10 days followed by reloading
through normal ambulation. During the unloading period, soleus muscle fibre cross
section decreased by 38%. Prior to the onset of reloading, mice received a series
of intraperitoneal injections of anti-F4/80, which binds a mouse macrophage
surface antigen. Although anti-F4/80 injections did not affect macrophage numbers
in soleus muscles at 2 days of reloading, macrophages were reduced by 86% at 4
days of reloading. Muscle membrane lysis during the reloading period did not
differ at 2 days of reloading between anti-F4/80-treated mice and mice that
received isotype control antibody. However, control animals showed large
decreases in the number of fibres with membrane lesions at 4 days of reloading,
but this membrane repair did not occur in macrophage-depleted mice. Macrophage
depletion also reduced muscle regeneration (indicated by central nucleation) and
satellite cell differentiation (indicated by reductions in MyoD-expressing
satellite cells) and prevented growth of muscle fibres that normally occurred in
control animals between days 2 and 4 of reloading. These findings collectively
show that macrophages play a significant role in muscle fibre membrane repair,
regeneration and growth during increased muscle use after a period of atrophy.
PMID- 17038434
TI - Mechanosensitive currents in the neurites of cultured mouse sensory neurones.
AB - Almost all sensory neurones in the dorsal root ganglia have a mechanosensory
function. The transduction of mechanical stimuli in vivo takes place exclusively
at the sensory ending. For cutaneous sensory receptors it has so far proved
impossible to directly record the mechanically gated receptor potential because
of the small size and inaccessibility of the sensory ending. Here we investigate
whether mechanosensitive currents are present in the neurites of freshly isolated
adult mouse sensory neurones in culture. Almost all sensory neurone neurites
possess currents gated by submicrometre displacement stimuli (92%). Three types
of mechanically activated conductance were characterized based on different
inactivation kinetics. A rapidly adapting conductance was found in larger sensory
neurones with narrow action potentials characteristic of mechanoreceptors. Slowly
and intermediate adapting conductances were found exclusively in putative
nociceptive neurones. Mechanically activated currents with similar kinetics were
found also after stimulating the cell soma. However, soma currents were only
observed in around 60% of cells tested and the displacement threshold was several
times larger than for the neurite (approximately 6 microm). The reversal
potential of the rapidly adapting current indicated that this current is largely
selective for sodium ions whereas the slowly adapting current is non-selective.
It is likely that distinct ion channel entities underlie these two currents. In
summary, our data suggest that the high sensitivity and robustness of
mechanically gated currents in the sensory neurite make this a useful in vitro
model for the mechanosensitive sensory endings in vivo.
PMID- 17038435
TI - Myoglobin translational diffusion in rat myocardium and its implication on
intracellular oxygen transport.
AB - Current theory of respiratory control invokes a role of myoglobin (Mb)
facilitated O2 diffusion in regulating the intracellular O2 flux, provided Mb
diffusion can compete effectively with free O2 diffusion. Pulsed-field gradient
NMR methods have now followed gradient-dependent changes in the distinct 1H NMR
gamma CH3 Val E11 signal of MbO2 in perfused rat myocardium to obtain the
endogenous Mb translational diffusion coefficient (D(Mb)) of 4.24 x 10(-7) cm2 s(
1) at 22 degrees C. The D(Mb) matches precisely the value predicted by in vivo
NMR rotational diffusion measurements of Mb and shows no orientation preference.
Given values in the literature for the Krogh's free O2 diffusion coefficient
(K0), myocardial Mb concentration and a partial pressure of O2 that half
saturates Mb (P50), the analysis yields an equipoise diffusion P(O2) of 1.77
mmHg, where Mb and free O2 contribute equally to the O2 flux. In the myocardium,
Mb-facilitated O2 diffusion contributes increasingly more than free O2 diffusion
when the P(O2) falls below 1.77 mmHg. In skeletal muscle, the P(O2) must fall
below 5.72 mmHg. Altering the Mb P50 induces modest change. Mb-facilitated
diffusion has a higher poise in skeletal muscle than in myocardium. Because the
basal P(O2) hovers around 10 mmHg, Mb does not have a predominant role in
facilitating O2 transport in myocardium but contributes significantly only when
cellular oxygen falls below the equipoise diffusion P(O2).
PMID- 17038437
TI - Power spectral analysis in mice: What are the appropriate frequency bands?
PMID- 17038436
TI - The electrogenicity of the rat sodium-bicarbonate cotransporter NBCe1 requires
interactions among transmembrane segments of the transporter.
AB - The electrogenic Na+-HCO3- cotransporter (NBCe1) plays a central role in
intracellular pH (pHi) regulation as well as HCO3- secretion by pancreatic ducts
and HCO3- reabsorption by renal proximal tubules. To understand the structural
requirements for the electrogenicity of NBCe1, we constructed chimeras of NBCe1-A
and the electroneutral NBCn1-B, and used two-electrode voltage clamp to measure
electrogenic transporter current in Xenopus oocytes exposed to 5% CO2-26 mm HCO3-
(pH 7.40). The chimera consisting of NBCe1-A (i.e. NBCe1-A 'background') with the
cytoplasmic N-terminal domain (Nt) of NBCn1-B had a reversal potential of -156.3
mV (compared with a membrane potential Vm of -43.1 mV in a HCO3(-)-free solution)
and a slope conductance of 3.0 microS (compared with 12.5 microS for NBCe1-A).
Also electrogenic were chimeras with an NBCe1-A background but with NBCn1-B
contributing the extracellular loop (L) between transmembrane segment (TM) 5 and
6 (-140.9 mV/11.1 microS), the cytoplasmic C-terminal domain (Ct; -123.8 mV/9.7
microS) or Nt + L + Ct (-120.9 mV/3.7 microS). Reciprocal chimeras (with an NBCn1
background but with NBCe1 contributing Nt, L, Ct or Nt + L + Ct) produced no
measurable electrogenic transporter currents in the presence of CO2-HCO3-. pHi
recovered from an acid load, but without the negative shift of Vm that is
characteristic of electrogenic Na+-HCO3- cotransporters. Thus, these chimeras
were electroneutral, as were two others consisting of NBCe1(Nt-L)/NBCn1(TM6-Ct)
and NBCn1(Nt-L)/NBCe1(TM6-Ct). We propose that the electrogenicity of NBCe1
requires interactions between TM1-5 and TM6-13.
PMID- 17038439
TI - Hemodynamic analysis of Hyrtl anastomosis in human placenta.
AB - The Hyrtl anastomosis is a common connection between the umbilical arteries near
the cord insertion in most human placentas. It has been speculated that it
equalizes the blood pressure between the territories supplied by the umbilical
arteries. However, its functional role in the regulation and distribution of
fetal blood flow to the placenta has not yet been explored. A computational model
has been developed for quantitative analysis of hemodynamic characteristic of the
Hyrtl anastomosis in cases of discordant blood flow in the umbilical arteries.
Simulations were performed for cases of either increased placental resistance at
the downstream end or reduced arterial blood flow due to some pathologies
upstream of one of the arteries. The results indicate that when placental
territories of one artery impose increased resistance to fetal blood flow, the
Hyrtl anastomosis redistributes the blood flow into the second artery to reduce
the large pressure gradients that are developed in the affected artery. When one
of the arteries conducts a smaller blood flow into the placenta and a relatively
smaller pressure gradient is developed, the Hyrtl anastomosis rebuilds the
pressure gradients in the affected artery and redistributes blood flow from the
unaffected artery to the affected one to improve placental perfusion. In
conclusion, the Hyrtl anastomosis plays the role of either a safety valve or a
pressure stabilizer between the umbilical arteries at the placental insertion.
PMID- 17038438
TI - Optimal frequency ranges for extracting information on cardiovascular autonomic
control from the blood pressure and pulse interval spectrograms in mice.
AB - The analysis of blood pressure (BP) and heart rate (HR) variability by spectral
methods has proven a useful tool in many animal species for the assessment of the
vagal and sympathetic contributions to oscillations of BP and HR. Continuous BP
measurements obtained in mice by telemetry were used to characterize the spectral
bandwidths of autonomic relevance by using an approach with no a priori. The
paradigm was based on the autonomic blockades obtained with conventional drugs
(atropine, prazosin, atenolol). The spectral changes were estimated in all of the
combinations of spectral bandwidths. The effect of hydralazine was also tested
using the same systematic analysis, to detect the zones of sympathetic activation
resulting reflexly from the vasodilatory action of the drug. Two zones of
interest in the study of the autonomic control of BP and HR were observed. The
first zone covered the 0.15-0.60 Hz range of the systolic BP spectrum and
corresponds to the low-frequency zone (or Mayer waves). This zone reflects
sympathetic control since the power spectral density of this zone was
significantly reduced with alpha1-adrenoceptor blockade (prazosin), while it was
significantly amplified as a result of a reflex sympathetic activation
(hydralazine). The second zone covered the 2.5-5.0 Hz range of the pulse interval
spectrum and corresponded to the high-frequency zone (respiratory sinus
arrhythmia) under vagal control (blocked by atropine). These zones are
recommended for testing the autonomic control of circulation in mice.
PMID- 17038440
TI - Oxyntomodulin increases intrinsic heart rate in mice independent of the glucagon
like peptide-1 receptor.
AB - Oxyntomodulin (OXM), a postprandially released intestinal hormone, inhibits food
intake via the glucagon-like peptide-1 receptor (GLP-1R). Although OXM may have
clinical value in treating obesity, the cardiovascular effects of OXM are not
well understood. Using telemetry to measure heart rate (HR), body temperature
(Tb), and activity in conscious and freely moving mice, we tested 1) whether OXM
affects HR and 2) whether this effect is mediated by the GLP-1R. We found that
peripherally administered OXM significantly increased HR in wild-type mice,
raising HR by >200 beats/min to a maximum of 728 +/- 11 beats/min. To determine
the extent to which the sympathetic nervous system mediates the tachycardia of
OXM, we delivered this hormone to mice deficient in dopamine-beta-hydroxylase
[Dbh(-/-) mice], littermate controls [Dbh(+/-) mice], and autonomically blocked
C57Bl mice. OXM increased HR equally in all groups (192 +/- 13, 197 +/- 21, and
216 +/- 11 beats/min, respectively), indicating that OXM elevated intrinsic HR.
Intrinsic HR was also vigorously elevated by OXM in Glp-1R(-/-) mice (200 +/- 28
beats/min). In addition, peripherally administered OXM inhibited food intake and
activity levels in wild-type mice and lowered Tb in autonomically blocked mice.
None of these effects were observed in Glp-1R(-/-) mice. These data suggest
multiple modes of action of OXM: 1) it directly elevates murine intrinsic HR
through a GLP-1R-independent mechanism, perhaps via the glucagon receptor or an
unidentified OXM receptor, and 2) it lowers food intake, activity, and Tb in a
GLP-1R-dependent fashion.
PMID- 17038441
TI - Sex-related effects on venous compliance and capillary filtration in the lower
limb.
AB - Recent studies in humans have suggested sex differences in venous compliance of
the lower limb, with lower compliance in women. Capillary fluid filtration could,
however, be a confounder in the evaluation of venous compliance. The venous
capacitance and capillary filtration response in the calves of 12 women (23.2 +/-
0.5 years) and 16 men (22.9 +/- 0.5 years) were studied during 8 min lower body
negative pressure (LBNP) of 11, 22, and 44 mmHg. Calf venous compliance is
dependent on pressure and was determined using the first derivative of a
quadratic regression equation that described the capacitance-pressure
relationship [compliance = beta1 + (2 x beta2 x transmural pressure)]. We found a
lower venous compliance in women at low transmural pressures, and the venous
capacitance in men was increased (P < 0.05). However, the difference in
compliance between sexes was reduced and not seen at higher transmural pressures.
Net capillary fluid filtration and capillary filtration coefficient (CFC) were
greater in women than in men during LBNP (P < 0.05). Furthermore, calf volume
increase (capacitance response + total capillary filtration) during LBNP was
equivalent in both sexes. When total capillary filtration was not subtracted from
the calf capacitance response in the calculation of venous compliance, the sex
differences disappeared, emphasizing that venous compliance measurement should be
corrected for the contribution of CFC.
PMID- 17038442
TI - Sex differences in energy metabolism and performance of teleost cardiac tissue.
AB - This study examined the effects of different oxygenation levels and substrate
availability on cardiac performance, metabolism, and biochemistry in sexually
immature male and female rainbow trout (Oncorhynchus mykiss). Ventricle strips
were electrically paced (0.5 Hz, 14 degrees C) in hyperoxic or hypoxic Ringer
solution. Our results demonstrate that 1) males sustain isometric force
production (F) longer than females under hyperoxia (P O2 = 640 mmHg) with
exogenous glucose present; 2) contractility is not maintained under moderate (P
O2 = 130 mmHg) or severe hypoxia (P O2 = 10-20 mmHg) with glucose in either sex;
however, following reoxygenation, F is higher in females compared with males; and
3) female tissue has higher lactate levels, net lactate efflux, and lactate
dehydrogenase activity than males, whereas males have higher glycogen, citrate
synthase, and beta-hydroxy acyl-CoA dehydrogenase activities, and greater
inotropic responses to exogenous glucose and octanoate. No sex differences were
detected in responsiveness to epinephrine and inhibitors of glucose transport or
activities of hexokinase and pyruvate kinase. We conclude that sex differences
exist in rainbow trout cardiac tissue: females appear to prefer glycolysis for
ATP production, whereas males have a higher capacity for aerobic and lipid
metabolism.
PMID- 17038443
TI - Myofilament response to Ca2+ and Na+/H+ exchanger activity in sex hormone-related
protection of cardiac myocytes from deactivation in hypercapnic acidosis.
AB - Compared to sham-operated controls, myofilaments from hearts of ovariectomized
(OVX) rats demonstrate an increase in Ca2+ sensitivity with no change in maximum
tension (Wattanapermpool J and Reiser PJ. Am J Physiol 277: H467-H473, 1999). To
test the significance of this modification in intact cells, we compared
intracellular Ca2+ transients and shortening of ventricular myocytes isolated
from sham and 10-wk OVX rats. There was a decrease in the peak Ca2+ transient
with prolonged 50% decay time in OVX cardiac myocytes without changes in the
resting intracellular Ca2+ concentration. Percent cell shortening was also
depressed, and relaxation was prolonged in cardiac myocytes from OVX rats
compared with shams. Ovariectomy induced a sensitization of the myofilaments to
Ca2+. Hypercapnic acidosis suppressed the shortening of OVX myocytes to a lesser
extent than that detected in shams. Moreover, a larger compensatory increase in
%cell shortening was obtained in OVX myocytes during prolonged acidosis. The
elevated compensation in cell shortening was related to a higher amount of
increase in the amplitude of the Ca2+ transient in OVX myocytes. However, these
differences in Ca2+ transients and %cell shortening were no longer evident in the
presence of 1 microM cariporide, a specific inhibitor of Na+/H+ exchanger type 1
(NHE1). Our results indicate that deprivation of female sex hormones modulates
the intracellular Ca2+ concentration in cardiac myocytes, possibly via an
increased NHE1 activity, which may act in concert with Ca2+ hypersensitivity of
myofilament activation as a determinant of sex differences in cardiac function.
PMID- 17038444
TI - Hypersensitivity of myofilament response to Ca2+ in association with
maladaptation of estrogen-deficient heart under diabetes complication.
AB - The amelioration of cardioprotective effect of estrogen in diabetes suggests
potential interactive action of estrogen and insulin on myofilament activation.
We compared Ca2+-dependent Mg2+-ATPase activity of isolated myofibrillar
preparations from hearts of sham and 10-wk ovariectomized rats with or without
simultaneous 8 wk-induction of diabetes and from diabetic-ovariectomized rats
with estrogen and/or insulin supplementation. Similar magnitude of suppressed
maximum myofibrillar ATPase activity was demonstrated in ovariectomized,
diabetic, and diabetic-ovariectomized rat hearts. Such suppressed activity and
the relative suppression in alpha-myosin heavy chain level in ovariectomy
combined with diabetes could be completely restored by estrogen and insulin
supplementation. Conversely, the myofilament Ca2+ hypersensitivity detected only
in the ovariectomized but not diabetic group was also observed in diabetic
ovariectomized rats, which was restored upon estrogen supplementation. Binding
kinetics of beta1-adrenergic receptors and immunoblots of beta1-adrenoceptors as
well as heat shock 72 (HSP72) were analyzed to determine the association of
changes in receptors and HSP72 to that of the myofilament response to Ca2+. The
amount of beta1-adrenoceptors significantly increased concomitant with Ca2+
hypersensitivity of the myofilament, without differences in the receptor binding
affinity among the groups. In contrast, changes in HSP72 paralleled that of
maximum myofibrillar ATPase activity. These results indicate that
hypersensitivity of cardiac myofilament to Ca2+ is specifically induced in
ovariectomized rats even under diabetes complication and that alterations in the
expression of beta1-adrenoceptors may, in part, play a mechanistic role
underlying the cardioprotective effects of estrogen that act together with Ca2+
hypersensitivity of the myofilament in determining the gender difference in
cardiac activation.
PMID- 17038445
TI - Role of glucocorticoid receptor in acclimation of killifish (Fundulus
heteroclitus) to seawater and effects of arsenic.
AB - Killifish are euryhaline teleosts that adapt to rapid changes in the salinity of
the seawater. It is generally accepted that acclimation to seawater is mediated
by cortisol activation of the glucocorticoid receptor (GR), which stimulates CFTR
mRNA expression and CFTR-mediated Cl- secretion by the gill. Because there is no
direct evidence in killifish that the GR stimulates CFTR gene expression,
quantitative PCR studies were conducted to test the hypothesis that cortisol
activation of GR upregulates CFTR mRNA expression and that this response is
required for acclimation to seawater. Inhibition of the GR by RU-486 prevented
killifish from acclimating to increased salinity and blocked the increase in CFTR
mRNA. In contrast, inhibition of the mineralocorticoid receptor by spironolactone
had no effect on acclimation to seawater. Thus acclimation to increased salinity
in killifish requires signaling via the GR and includes an increase in CFTR gene
expression. Because arsenic, a toxic metalloid that naturally occurs in the
aquatic environment, has been shown to disrupt GR transcriptional regulation in
avian and mammalian systems, studies were also conducted to determine whether
arsenic disrupts cortisol-mediated activation of CFTR gene expression in this in
vivo fish model and thereby blocks the ability of killifish to acclimate to
increased salinity. Arsenic prevented acclimation to seawater and decreased CFTR
protein abundance. However, arsenic did not disrupt the GR-induced increase in
CFTR mRNA. Thus arsenic blocks acclimation to seawater in killifish by a
mechanism that does not disrupt GR-mediated induction of CFTR gene expression.
PMID- 17038446
TI - Nitric oxide impairs baroreflex gain during acute psychological stress.
AB - Psychological stress can suppress baroreflex function, but the mechanism has not
been fully elucidated. Nitric oxide in the brain and in the adrenal cortex, as
well as plasma glucocorticoids, increases during stress and has been shown to
suppress reflex gain in unstressed animals. Therefore, the purpose of this study
was to test the hypothesis that stress, caused by exposure to a novel
environment, decreases baroreflex gain in rabbits through the actions of nitric
oxide to increase corticosterone release. Baroreflex control of heart rate and
plasma corticosterone levels was quantified before and after blockade of nitric
oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NNA; 20 mg/kg iv) in
conscious rabbits exposed to a novel environment and in the same rabbits once
they had been conditioned to the environment. Stress significantly reduced
baroreflex gain from -23.4 +/- 2 to -12.2 +/- 1.6 beats x min(-1) x mmHg(-1) (P <
0.05) and increased plasma corticosterone levels from 5.4 +/- 0.7 to 15.5 +/- 5.0
ng/ml (P < 0.05). NOS blockade increased gain in stressed animals (to -27.2 +/-
5.4 beats x min(-1) x mmHg(-1), P < 0.05) but did not alter gain in unstressed
rabbits (-26.8 +/- 4.9 beats x min(-1) x mmHg(-1)) such that gain was equalized
between the two states. NOS blockade increased plasma corticosterone levels in
unstressed animals (to 14.3 +/- 2.1 ng/ml, P < 0.05) but failed to significantly
alter levels in stressed rabbits (14.0 +/- 3.9 ng/ml). In conclusion,
psychological stress may act via nitric oxide, independently of increases in
corticosterone, to decrease baroreflex gain.
PMID- 17038447
TI - Gill Na+-K+-ATPase activity correlates with basolateral membrane lipid
composition in seawater- but not freshwater-acclimated Arctic char (Salvelinus
alpinus).
AB - The successful migration of euryhaline teleost fish from freshwater to seawater
requires the upregulation of gill Na+-K+-ATPase, an ion transport enzyme located
in the basolateral membrane (BLM) of gill chloride cells. Following 39 days of
seawater exposure, Arctic char had similar plasma sodium and chloride levels as
individuals maintained in freshwater, indicating they had successfully acclimated
to seawater. This acclimation was associated with an eightfold increase in gill
Na+-K+-ATPase activity but only a threefold increase in gill Na+-K+-ATPase
protein number, suggesting that other mechanisms may also modulate gill Na+-K+
ATPase activity. We therefore investigated the influence of membrane composition
on Na+-K+-ATPase activity by examining the phospholipid, fatty acid, and
cholesterol composition of the gill BLM from freshwater- and seawater-acclimated
Arctic char. Mean gill BLM cholesterol content was significantly lower (
approximately 22%) in seawater-acclimated char. Gill Na+-K+-ATPase activity in
individual seawater Arctic char was negatively correlated with BLM cholesterol
content and positively correlated with %phosphatidylethanolamine and overall
%18:2n6 (linoleic acid) content of the BLM, suggesting gill Na+-K+-ATPase
activity of seawater-acclimated char may be modulated by the lipid composition of
the BLM and may be especially sensitive to those parameters known to influence
membrane fluidity. Na+-K+-ATPase activity of individual freshwater Arctic char
was not correlated to any membrane lipid parameter measured, suggesting that
different lipid-protein interactions may exist for char living in each
environment.
PMID- 17038448
TI - Evolutionary model selection with a genetic algorithm: a case study using stem
RNA.
AB - The choice of a probabilistic model to describe sequence evolution can and should
be justified. Underfitting the data through the use of overly simplistic models
may miss out on interesting phenomena and lead to incorrect inferences.
Overfitting the data with models that are too complex may ascribe biological
meaning to statistical artifacts and result in falsely significant findings. We
describe a likelihood-based approach for evolutionary model selection. The
procedure employs a genetic algorithm (GA) to quickly explore a combinatorially
large set of all possible time-reversible Markov models with a fixed number of
substitution rates. When applied to stem RNA data subject to well-understood
evolutionary forces, the models found by the GA 1) capture the expected overall
rate patterns a priori; 2) fit the data better than the best available models
based on a priori assumptions, suggesting subtle substitution patterns not
previously recognized; 3) cannot be rejected in favor of the general reversible
model, implying that the evolution of stem RNA sequences can be explained well
with only a few substitution rate parameters; and 4) perform well on simulated
data, both in terms of goodness of fit and the ability to estimate evolutionary
rates. We also investigate the utility of several distance measures for comparing
and contrasting inferred evolutionary models. Using widely available small
computer clusters, our approach allows, for the first time, to evaluate the
performance of existing RNA evolutionary models by comparing them with a large
pool of candidate models and to validate common modeling assumptions. In
addition, the new method provides the foundation for rigorous selection and
comparison of substitution models for other types of sequence data.
PMID- 17038449
TI - Predicting gene expression level from codon usage bias.
AB - The "expression measure" of a gene, E(g), is a statistic devised to predict the
level of gene expression from codon usage bias. E(g) has been used extensively to
analyze prokaryotic genome sequences. We discuss 2 problems with this approach.
First, the formulation of E(g) is such that genes with the strongest selected
codon usage bias are not likely to have the highest predicted expression levels;
indeed the correlation between E(g) and expression level is weak among moderate
to highly expressed genes. Second, in some species, highly expressed genes do not
have unusual codon usage, and so codon usage cannot be used to predict expression
levels. We outline a simple approach, first to check whether a genome shows
evidence of selected codon usage bias and then to assess the strength of bias in
genes as a guide to their likely expression level; we illustrate this with an
analysis of Shewanella oneidensis.
PMID- 17038450
TI - Controlling the obesity epidemic is important for maintaining musculoskeletal
health.
PMID- 17038451
TI - Obesity and osteoarthritis: more complex than predicted!
PMID- 17038452
TI - Reduction of leucocyte telomere length in radiographic hand osteoarthritis: a
population-based study.
AB - BACKGROUND: Although age is the strongest predictor of osteoarthritis, the exact
mechanism underlying this disorder remains elusive. OBJECTIVE: To examine the
association between leucocyte telomere length (LTL), a bio-indicator of ageing,
and radiographic hand osteoarthritis. METHODS: An unselected, predominantly
female sample from the TwinsUK Adult Twin Registry (Twin Research and Genetic
Epidemiology Unit, St Thomas Hospital, London, UK) was studied. Radiographs of
both hands were obtained with a standard posteroanterior view and assessed for
radiographic osteoarthritis according to the Kellgren/Lawrence (K/L) score.
Individual radiographic features including osteophytes and joint space narrowing
(JSN) were also assessed on a four-point scale using a standard atlas. Hand
osteoarthritis was defined radiographically as having >or=3 osteoarthritis
affected joints of both hands (K/L score>or=2). Severity of hand osteoarthritis
was indicated semiquantitatively by total K/L scores, osteophytes, JSN scores and
proportion of joints affected. Mean LTL was measured by the terminal restriction
fragment length using the Southern blot. RESULTS: A total of 1086 Caucasian
subjects (mean (SD) age 55 (8.0) years) were studied. LTL was 6.95 (0.64) kb and
was inversely correlated with age. After adjustment for age, sex, body mass index
and smoking, LTL was significantly shorter by 178 bp in subjects with hand
osteoarthritis (n = 160) than in those without (n = 926; p = 0.04). LTL was also
significantly associated with semicontinuous measures of osteoarthritis (eg,
total K/L score, JSN score, osteophyte score and proportion of joints affected)
after adjustment (all p3 yr) spinal cord injury (SCI) and 10 able-bodied controls (CTRL). Chemically
skinned fibers were tested for active and passive mechanical characteristics and
subsequently classified according to myosin heavy chain (MHC) content. SCI
individuals had smaller proportions of type I (11 +/- 7 vs. 34 +/- 5%) and IIa
fibers (11 +/- 6 vs. 31 +/- 5%), whereas type IIx fibers were more frequent (40
+/- 13 vs. 7 +/- 3%) compared with CTRL subjects (P < 0.05). Cross-sectional area
and peak force were similar in both groups for all fiber types. Unloaded
shortening velocity of fibers from paralyzed muscles was higher in type IIa,
IIa/IIx, and IIx fibers (26, 65, and 47%, respectively; P < 0.01). Consequently,
absolute peak power was greater in type IIa (46%; P < 0.05) and IIa/IIx fibers
(118%; P < 0.01) of the SCI group, whereas normalized peak power was higher in
type IIa/IIx fibers (71%; P < 0.001). Ca(2+) sensitivity and passive fiber
characteristics were not different between the two groups in any fiber type.
Composite values (average value across all fibers analyzed within each study
participant) showed similar results for cross-sectional area and peak force,
whereas maximal contraction velocity and fiber power were more than 100% greater
in SCI individuals. These data illustrate that contractile performance is
preserved or even higher in the remaining fibers of human muscles following
reduced neuromuscular activity.
PMID- 17038492
TI - Muscle pain induces task-dependent changes in cervical agonist/antagonist
activity.
AB - This study examined the effect of experimental neck muscle pain on the EMG-force
relationship of cervical agonist and antagonist muscles. Surface EMG signals were
detected from the sternomastoid, splenius capitis, and upper trapezius muscles
bilaterally from 14 healthy subjects during cervical flexion and extension
contractions of linearly increasing force from 0 to 60% of the maximum voluntary
contraction (MVC). Measurements were performed before and after injection of 0.5
ml hypertonic and isotonic saline into either the sternomastoid or splenius
capitis in two experimental sessions. EMG average rectified value (ARV) of the
sternomastoid, splenius capitis, and upper trapezius muscles and the muscle fiber
conduction velocity (CV) of the sternomastoid muscle were estimated at 5% MVC
force increments. During cervical flexion with injection of hypertonic saline in
sternomastoid, ARV of sternomastoid was lower on the side of pain in the force
range 25-60% MVC (P < 0.05) and was associated with a bilateral reduction of
splenius capitis and upper trapezius ARV (P < 0.01). During cervical extension,
injection of hypertonic saline in splenius capitis resulted in lower estimates of
splenius capitis ARV on the painful side from 45 to 60% MVC (P < 0.05), which was
associated with a bilateral increase in upper trapezius ARV estimates from 50 to
60% MVC (P < 0.001). However, no significant change was identified for estimates
of sternomastoid ARV. Experimentally induced neck muscle pain resulted in task
dependent changes in cervical agonist/antagonist activity without modifications
in muscle fiber CV.
PMID- 17038493
TI - Imaging of the pulmonary circulation in the closed-chest rat using synchrotron
radiation microangiography.
AB - Structural changes of the pulmonary circulation during the pathogenesis of
pulmonary arterial hypertension remain to be fully elucidated. Although
angiography has been used for visualizing the pulmonary circulation, conventional
angiography systems have considerable limitations for visualizing small
microvessels (diameters < 200 microm), particularly within a closed-chest animal
model. In this study we assess the effectiveness of monochromatic synchrotron
radiation (SR) for microangiography of the pulmonary circulation in the intact
chest rat. Male adult Sprague-Dawley rats were anesthetized, and a catheter was
positioned within the right ventricle, for administering iodinated contrast agent
(Iomeron 350). Subsequently, microangiography of pulmonary arterial branches
within the left lung was performed using monochromatic SR. Additionally, we
assessed dynamic changes in vessel diameter during acute hypoxic (10% and 8% O2
for 4 min each) pulmonary vasoconstriction (HPV). Using SR we were able to
visualize pulmonary microvessels with a diameter of <100 microm (the 4th
generation of branching from the left axial artery). Acute hypoxia caused a
significant decrease in the diameter of all vessels less than 500 microm. The
greatest degree of pulmonary vasoconstriction was observed in vessels with a
diameter between 200 and 300 microm. These results demonstrate the effectiveness
of SR for visualizing pulmonary vessels in a closed-chest rat model and for
assessing dynamic changes associated with HPV. More importantly, these
observations implicate SR as an effective tool in future research for assessing
gross structural changes associated with the pathogenesis of pulmonary arterial
hypertension.
PMID- 17038494
TI - ANP signaling inhibits TGF-beta-induced Smad2 and Smad3 nuclear translocation and
extracellular matrix expression in rat pulmonary arterial smooth muscle cells.
AB - Atrial natriuretic peptide (ANP) and transforming growth factor (TGF)-beta play
important counterregulatory roles in pulmonary vascular adaptation to chronic
hypoxia. To define the molecular mechanism of this important interaction, we
tested whether ANP-cGMP-protein kinase G (PKG) signaling inhibits TGF-beta1
induced extracellular matrix (ECM) expression and defined the specific site(s) at
which this molecular merging of signaling pathways occurs. Rat pulmonary arterial
smooth muscle cells (PASMCs) were treated with ANP (1 muM) or cGMP (1 mM) with or
without pretreatment with PKG inhibitors KT-5823 (1 muM) or Rp-8-bromo-cGMP (Rp-8
Br-cGMP 50 muM), then exposed to TGF-beta1 (1 ng/ml) for 5-360 min (for pSmad
nuclear translocation and protein analysis) or 24 h (for ECM mRNA expression).
Nuclear translocation of pSmad2 and pSmad3 was assessed by fluorescent confocal
microscopy. ANP and cGMP inhibited TGF-beta1-induced pSmad2 and pSmad3 nuclear
translocation and expression of periostin, osteopontin, and plasminogen activator
inhibitor-1 mRNA and protein, but not TGF-beta1-induced phosphorylation of Smad2
and Smad3. KT-5823 and Rp-8-Br-cGMP blocked ANP/cGMP-induced activation of PKG
and inhibition of TGF-beta1-stimulated nuclear translocation of pSmad2 and pSmad3
in PASMCs. These results reveal for the first time a precise site at which ANP
cGMP-PKG signaling exerts its antifibrogenic effect on the profibrogenic TGF
beta1 signaling pathway: by blocking TGF-beta1-induced pSmad2 and pSmad3 nuclear
translocation and ECM expression in PASMCs. Blocking nuclear translocation and
subsequent binding of pSmad2 and pSmad3 to TGF-beta-Smad response elements in ECM
genes may be responsible for the inhibitory effects of ANP on TGF-beta-induced
expression of ECM molecules.
PMID- 17038495
TI - Hydrogen sulfide and its possible roles in myocardial ischemia in experimental
rats.
AB - The role of hydrogen sulfide (H(2)S) in myocardial infarction (MI) has not been
previously studied. We therefore investigated the effect of H(2)S in a rat model
of MI in vivo. Animals were randomly divided into three groups (n = 80) and
received either vehicle, 14 micromol/kg of sodium hydrosulfide (NaHS), or 50
mg/kg propargylglycine (PAG) everyday for 1 wk before surgery, and the treatment
was continued for a further 2 days after MI when the animals were killed. The
mortality was 35% in vehicle-treated, 40% in PAG-treated, and 27.5% in NaHS
treated (P < 0.05 vs. vehicle) groups. Infarct size was 52.9 +/- 3.5% in vehicle
treated, 62.9 +/- 7.6% in PAG-treated, and 43.4 +/- 2.8% in NaHS-treated (P <
0.05 vs. vehicle) groups. Plasma H(2)S concentration was significantly increased
after MI (59.2 +/- 7.16 microM) compared with the baseline concentration (i.e.,
38.2 +/- 2.07 microM before MI; P < 0.05). Elevated plasma H(2)S after MI was
abolished by treatment of animals with PAG (39.2 +/- 5.02 microM). We further
showed for the first time cystathionine-gamma-lyase protein localization in the
myocardium of the infarct area by using immunohistochemical staining. In the
hypoxic vascular smooth muscle cells, we found that cell death was increased
under the stimuli of hypoxia but that the increased cell death was attenuated by
the pretreatment of NaHS (71 +/- 1.2% cell viability in hypoxic vehicle vs. 95 +/
2.3% in nonhypoxic control; P < 0.05). In conclusion, endogenous H(2)S was
cardioprotective in the rat model of MI. PAG reduced endogenous H(2)S production
after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H(2)S
might provide a novel approach to the treatment of MI.
PMID- 17038496
TI - Differences in potential for amino acid change after mutation reveals distinct
strategies for kappa and lambda light-chain variation.
AB - B cells generate varied yet functional clones under high rates of mutation of
their V genes. It has been proposed that as a result of the opposing demands of
diversification and preservation of integrity, the V genes of heavy and light
chains have evolved to overexpress codons prone to amino acid change in their
complementarity determining regions (CDR) compared with the framework (FW)
regions. We have analyzed the germ-line V genes of heavy and light chains (both
kappa and lambda), comparing codons of CDR and FW of the germ-line V regions both
to each other and to control regions. We found that in both germ-line heavy
chains and lambda chains, CDR codons are prone to replacement mutations, whereas
in the FW, the opposite is true. Furthermore, the difference between CDR and FW
in heavy chains and lambda chains is based on codons that are prone to
nonconservative changes of amino acid. In contrast, in germ-line kappa chains,
the codons in both CDR and FW are more prone to replacement mutations. We also
demonstrated that negative selection during immune responses is more sensitive to
nonconservative amino acid substitutions than overall amino acid change,
demonstrating the applicability of our analysis to real-time process of selection
in the immune system. The differences in germ-line kappa and lambda light chains'
potential reaction to mutation suggests that via these two differently evolved
light-chain types, the B cell repertoire encompasses two different strategies to
balance diversity and stability in an immune response.
PMID- 17038497
TI - Structural basis for mRNA and tRNA positioning on the ribosome.
AB - Protein synthesis requires the accurate positioning of mRNA and tRNA in the
peptidyl-tRNA site of the ribosome. Here we describe x-ray crystal structures of
the intact bacterial ribosome from Escherichia coli in a complex with mRNA and
the anticodon stem-loop of P-site tRNA. At 3.5-A resolution, these structures
reveal rearrangements in the intact ribosome that clamp P-site tRNA and mRNA on
the small ribosomal subunit. Binding of the anticodon stem-loop of P-site tRNA to
the ribosome is sufficient to lock the head of the small ribosomal subunit in a
single conformation, thereby preventing movement of mRNA and tRNA before mRNA
decoding.
PMID- 17038498
TI - Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4
tetraphosphate (Ap4A) and positron-emission tomography.
AB - Diadenosine-5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) and its analog P(2),P(3)
monochloromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate (AppCHClppA) are
competitive inhibitors of adenosine diphosphate-induced platelet aggregation,
which plays a central role in arterial thrombosis and plaque formation. In this
study, we evaluate the imaging capabilities of positron-emission tomography (PET)
with P(2),P(3)-[(18)F]monofluoromethylene diadenosine-5',5'''-P(1),P(4)
tetraphosphate ([(18)F]AppCHFppA) to detect atherosclerotic lesions in male New
Zealand White rabbits. Three to six months after balloon injury to the aorta, the
rabbits were injected with [(18)F]AppCHFppA, and microPET imaging showed rapid
accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta,
with lesions clearly visible 30 min after injection. Computed tomographic images
were coregistered with PET images to improve delineation of aortoiliac tracer
activity. Plaque macrophage density, quantified by immunostaining with RAM11
against rabbit macrophages, correlated with PET measurements of [(18)F]AppCHFppA
uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by
immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution
studies of [(18)F]AppCHFppA in normal rats indicated typical adenosine
dinucleotide behavior with insignificant myocardial uptake and fast kidney
clearance. The accumulation of [(18)F]AppCHFppA in macrophage-rich
atherosclerotic plaques can be quantified noninvasively with PET. Hence,
[(18)F]AppCHFppA holds promise for the noninvasive characterization of vascular
inflammation.
PMID- 17038499
TI - Branch-cut singularities in thermodynamics of Fermi liquid systems.
AB - The recently measured spin susceptibility of the two-dimensional electron gas
exhibits a strong dependence on temperature, which is incompatible with the
standard Fermi liquid phenomenology. In this article, we show that the observed
temperature behavior is inherent to ballistic two-dimensional electrons. Besides
the single-particle and collective excitations, the thermodynamics of Fermi
liquid systems includes effects of the branch-cut singularities originating from
the edges of the continuum of pairs of quasiparticles. As a result of the
rescattering induced by interactions, the branch-cut singularities generate
nonanalyticities in the thermodynamic potential that reveal themselves in
anomalous temperature dependences. Calculation of the spin susceptibility in such
a situation requires a nonperturbative treatment of the interactions. As in high
energy physics, a mixture of the collective excitations and pairs of
quasiparticles can effectively be described by a pole in the complex momentum
plane. This analysis provides a natural explanation for the observed temperature
dependence of the spin susceptibility, both in sign and in magnitude.
PMID- 17038500
TI - Ultrashort antibacterial and antifungal lipopeptides.
AB - Host-defense cationic antimicrobial peptides ( approximately 12-50 aa long) play
an essential protective role in the innate immune system of all organisms.
Lipopeptides, however, are produced only in bacteria and fungi during
cultivation, and they are composed of specific lipophilic moieties attached to
anionic peptides (six to seven amino acids). Here we report the following. (i)
The attachment of an aliphatic chain to otherwise inert, cationic D,L
tetrapeptides endows them with potent activity against various microorganisms
including antibiotic resistance strains. (ii) Cell specificity is determined by
the sequence of the short peptidic chain and the length of the aliphatic moiety.
(iii) Despite the fact that the peptidic chains are very short, their mode of
action involves permeation and disintegration of membranes, similar to that of
many long antimicrobial peptides. Besides adding important information on the
parameters necessary for host-defense lipopeptides to kill microorganisms, the
simple composition of these lipopeptides and their diverse specificities should
make them economically available, innate immunity-mimicking antimicrobial and
antifungal compounds for various applications.
PMID- 17038501
TI - Generic hydrophobic residues are sufficient to promote aggregation of the
Alzheimer's Abeta42 peptide.
AB - One hundred years ago, Alois Alzheimer observed a relationship between cognitive
impairment and the presence of plaque in the brains of patients suffering from
the disease that bears his name. The plaque was subsequently shown to be composed
primarily of a 42-residue peptide called amyloid beta (Abeta) 42. Despite the
importance of Abeta42 aggregation in the molecular etiology of Alzheimer's
disease, the amino acid sequence determinants of this process have yet to be
elucidated. Although stretches of hydrophobic residues in the C-terminal half of
Abeta42 have been implicated, the mechanism by which these residues promote
aggregation remains unclear. In particular, it is not known whether the side
chains of these hydrophobic residues mediate specific interactions that direct
self-assembly or, alternatively, whether hydrophobicity per se at these positions
is sufficient to promote aggregation. To distinguish between these two
possibilities, we substituted 12 hydrophobic residues in the C-terminal half of
Abeta42 with random nonpolar residues. The mutant sequences were screened by
using a fusion of Abeta42 to GFP. Because aggregation of Abeta42 prevents folding
of the GFP reporter, this screen readily distinguishes aggregating from
nonaggregating variants of Abeta42. Application of the screen demonstrated that,
despite the presence of 8-12 mutations, all of the sequences aggregated. To
confirm these results, several of the mutant sequences were prepared as synthetic
peptides and shown to form amyloid fibrils similar to those of WT Abeta42. These
findings indicate that hydrophobic stretches in the sequence of Abeta42, rather
than specific side chains, are sufficient to promote aggregation.
PMID- 17038502
TI - A tunable algorithm for collective decision-making.
AB - Complex biological systems are increasingly understood in terms of the algorithms
that guide the behavior of system components and the information pathways that
link them. Much attention has been given to robust algorithms, or those that
allow a system to maintain its functions in the face of internal or external
perturbations. At the same time, environmental variation imposes a complementary
need for algorithm versatility, or the ability to alter system function
adaptively as external circumstances change. An important goal of systems biology
is thus the identification of biological algorithms that can meet multiple
challenges rather than being narrowly specified to particular problems. Here we
show that emigrating colonies of the ant Temnothorax curvispinosus tune the
parameters of a single decision algorithm to respond adaptively to two distinct
problems: rapid abandonment of their old nest in a crisis and deliberative
selection of the best available new home when their old nest is still intact. The
algorithm uses a stepwise commitment scheme and a quorum rule to integrate
information gathered by numerous individual ants visiting several candidate
homes. By varying the rates at which they search for and accept these candidates,
the ants yield a colony-level response that adaptively emphasizes either speed or
accuracy. We propose such general but tunable algorithms as a design feature of
complex systems, each algorithm providing elegant solutions to a wide range of
problems.
PMID- 17038503
TI - Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted
Rag2-/-gamma c-/- mice.
AB - Because of species selectivity, HIV research is largely restricted to in vitro or
clinical studies, both limited in their ability to rapidly assess new strategies
to fight the virus. To prospectively study some aspects of HIV in vivo,
immunodeficient mice, transplanted with either human peripheral blood leukocytes
or human fetal tissues, have been developed. Although these are susceptible to
HIV infection, xenoreactivity, and short infection spans, resource and ethical
constraints, as well as biased HIV coreceptor tropic strain infection, pose
substantial problems in their use. Rag2(-/-)gamma(c)(-/-) mice, transplanted as
newborns with human CD34(+) cells, were recently shown to develop human B, T, and
dendritic cells, constituting lymphoid organs in situ. Here we tested these mice
as a model system for HIV-1 infection. HIV RNA levels peaked to up to 2 x 10(6)
copies per milliliter of plasma early after infection, and viremia was observed
for up to 190 days, the longest time followed. A marked relative CD4(+) T cell
depletion in peripheral blood occurred in CXCR4-tropic strain-infected mice,
whereas this was less pronounced in CCR5-tropic strain-infected animals. Thymus
infection was almost exclusively observed in CXCR4-tropic strain-infected mice,
whereas spleen and lymph node HIV infection occurred irrespective of coreceptor
selectivity, consistent with respective coreceptor expression on human CD4(+) T
cells. Thus, this straightforward to generate and cost-effective in vivo model
closely resembles HIV infection in man and therefore should be valuable to study
virus-induced pathology and to rapidly evaluate new approaches aiming to prevent
or treat HIV infection.
PMID- 17038504
TI - Characterization of the nanoscale properties of individual amyloid fibrils.
AB - We report the detailed mechanical characterization of individual amyloid fibrils
by atomic force microscopy and spectroscopy. These self-assembling materials,
formed here from the protein insulin, were shown to have a strength of 0.6 +/-
0.4 GPa, comparable to that of steel (0.6-1.8 GPa), and a mechanical stiffness,
as measured by Young's modulus, of 3.3 +/- 0.4 GPa, comparable to that of silk (1
10 GPa). The values of these parameters reveal that the fibrils possess
properties that make these structures highly attractive for future technological
applications. In addition, analysis of the solution-state growth kinetics
indicated a breakage rate constant of 1.7 +/- 1.3 x 10(-8) s(-1), which reveals
that a fibril 10 mum in length breaks spontaneously on average every 47 min,
suggesting that internal fracturing is likely to be of fundamental importance in
the proliferation of amyloid fibrils and therefore for understanding the
progression of their associated pathogenic disorders.
PMID- 17038505
TI - Direct magnetic resonance detection of neuronal electrical activity.
AB - Present noninvasive neuroimaging methods measure neuronal activity indirectly,
via either cerebrovascular changes or extracranial measurements of
electrical/magnetic signals. Recent studies have shown evidence that MRI may be
used to directly and noninvasively map electrical activity associated with human
brain activation, but results are inconclusive. Here, we show that MRI can detect
cortical electrical activity directly. We use organotypic rat-brain cultures in
vitro that are spontaneously active in the absence of a cerebrovascular system.
Single-voxel magnetic resonance (MR) measurements obtained at 7 T were highly
correlated with multisite extracellular local field potential recordings of the
same cultures before and after blockade of neuronal activity with tetrodotoxin.
Similarly, for MR images obtained at 3 T, the MR signal changed solely in voxels
containing the culture, thus allowing the spatial localization of the active
neuronal tissue.
PMID- 17038506
TI - Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell
differentiation and nuage/germinal granule formation in mice.
AB - Embryonic patterning and germ-cell specification in mice are regulative and
depend on zygotic gene activities. However, there are mouse homologues of
Drosophila maternal effect genes, including vasa and tudor, that function in
posterior and germ-cell determination. We report here that a targeted mutation in
Tudor domain containing 1/mouse tudor repeat 1 (Tdrd1/Mtr-1), a tudor-related
gene in mice, leads to male sterility because of postnatal spermatogenic defects.
TDRD1/MTR-1 predominantly localizes to nuage/germinal granules, an evolutionarily
conserved structure in the germ line, and its intracellular localization is
downstream of mouse vasa homologue/DEAD box polypeptide 4 (Mvh/Ddx4), similar to
Drosophila vasa-tudor. Tdrd1/Mtr-1 mutants lack, and Mvh/Ddx4 mutants show,
strong reduction of intermitochondrial cement, a form of nuage in both male and
female germ cells, whereas chromatoid bodies, another specialized form of nuage
in spermatogenic cells, are observed in Tdrd1/Mtr-1 mutants. Hence,
intermitochondrial cement is not a direct prerequisite for oocyte development and
fertility in mice, indicating differing requirements for nuage and/or its
components between male and female germ cells. The result also proposes that
chromatoid bodies likely have an origin independent of or additional to
intermitochondrial cement. The analogy between Mvh-Tdrd1 in mouse spermatogenic
cells and vasa-tudor in Drosophila oocytes suggests that this molecular pathway
retains an essential role(s) that functions in divergent species and in different
stages/sexes of the germ line.
PMID- 17038507
TI - Pharmacologic characterization of the cloned human trace amine-associated
receptor1 (TAAR1) and evidence for species differences with the rat TAAR1.
AB - The hemagglutinin-tagged human trace amine-associated receptor1 (TAAR1) was
stably coexpressed with rat Galpha(s) in the AV12-664 cell line, and receptor
activation was measured as the stimulation of cAMP formation. After blockade of
endogenously expressed alpha2- and beta-adrenoceptors with 2-[2-(2-methoxy-1,4
benzodioxanyl)]-imidazoline hydrochloride (2-methoxyidazoxan, RX821002) and
alprenolol, respectively, the resulting pharmacology was consistent with that of
a unique receptor subtype. beta-Phenylethylamine (beta-PEA), the putative
endogenous ligand, gave an EC50 of 106 +/- 5 nM in the assay. For a series of
beta-PEA analogs used to explore the pharmacophore, small substituents at ring
positions 3 and/or 4 generally resulted in compounds having lower potency than
beta-PEA, although several were as potent as beta-PEA. However, small
substituents at ring position 2 resulted in a number of compounds having
potencies as good as or better than beta-PEA. A number of nonselective
antagonists known to share affinity for multiple monoaminergic receptors were
evaluated for their ability to inhibit beta-PEA stimulation of the human TAAR1.
None had an IC50 <10 microM. For comparison, the rat TAAR1 receptor was expressed
in the AV12-664 cell line. A number of agonist compounds had significantly
different relative potencies between the rat and human TAAR1, demonstrating a
significant species difference between the rat and human TAAR1. The TAAR1
receptor exhibits a pharmacologic profile uniquely different from those of
classic monoaminergic receptors, consistent with the structural information that
places them in a distinct family of receptors. This unique pharmacologic profile
suggests the potential for development of TAAR-selective agonists and antagonists
to study their physiologic roles.
PMID- 17038508
TI - Marked strain differences in the pharmacokinetics of an alpha4beta1 integrin
antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro
(2S)-pyrrolidine-2-yl]-methoxybenzoic Acid (D01-4582), in Sprague-Dawley rats are
associated with albumin genetic polymorphism.
AB - Strain differences in pharmacokinetics of an alpha4beta1 integrin antagonist, 4
[1-[3-chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)
pyrrolidine-2-yl]methoxybenzoic acid (D01-4582), in Sprague-Dawley rat strains
(SD rat and CD rat) and their mechanism were investigated. Total plasma
clearances of D01-4582 were 31.5 and 5.23 ml/min/kg in SD and CD rats,
respectively. From in vivo studies, hepatic uptake process was thought to be
involved in the strain differences. Differences in the uptake of D01-4582 by
isolated hepatocytes prepared from the both strains were not observed when
hepatocytes were incubated with simple buffer, but marked differences were
observed when hepatocytes were incubated with plasma. When the dissociation
constants (Kd) for the plasma protein binding of D01-4582 were examined in six
rat strains, each strain was classified into two groups: a high-Kd group, which
included SD rats, Brown Norway rats, and Wistar rats; and a low-Kd group, which
included CD rats, Lewis rats, and Eisai hyperbilirubinemic rats. Since all rat
strains in the low-Kd group showed higher area under the concentration-time curve
for D01-4582 than rats in the high-Kd group, it was considered that the strain
differences in the pharmacokinetics of D01-4582 were due to differences in the
binding affinity. Purified albumin also showed strain differences in Kd. The cDNA
sequence of the albumin was analyzed, and 11 substitutions were observed. V238L
and T293I were found only in the high-Kd group, suggesting that these amino acid
changes reduced the binding affinity of albumin for D01-4582. In conclusion, the
strain differences in D01-4582 pharmacokinetics were suggested to be caused by an
alteration in Kd, associated with albumin genetic polymorphism.
PMID- 17038509
TI - Bias in estimation of transporter kinetic parameters from overexpression systems:
Interplay of transporter expression level and substrate affinity.
AB - The objective was to investigate the interplay between transporter expression
levels and substrate affinity in controlling the influence of aqueous boundary
layer (ABL) resistance on transporter kinetics in an over-expression system.
Taurocholate flux was measured across human apical sodium-dependent bile acid
transporter (hASBT)-Madin-Darby canine kidney monolayers on different occasions
and kinetic parameters estimated with and without considering ABL. In error-free
simulation/regression studies, flux values were generated across a range of J
max, Kt, and substrate concentrations. Similar evaluation was performed for
transport inhibition studies. Additionally, simulation/regression studies were
performed, incorporating 15% random error to estimate the probability of
successfully estimating Kt. Across different occasions, experimental J max and Kt
estimates for taurocholate were strongly associated (p < 0.001; r2 = 0.82) when
ABL was not considered. Simulation/regression results indicate that not
considering ABL caused this association, such that Kt estimates were highly
positively biased at high hASBT expression. In reanalyzing taurocholate flux data
using the ABL-present model, Kt was relatively constant across occasions
(approximately 5 microM) and not associated with J max (p = 0.24; r2 = 0.13).
Simulations suggest that J max and Kt collectively determined ABL influence,
which is most prominent under conditions of low monolayer resistance.
Additionally, not considering ABL lead to negatively biased Ki estimates,
especially at high J max. Error-inclusive simulation/regression studies indicated
that the probability of successfully estimating Kt depended on the contribution
of ABL resistance to flux; when flux became increasingly ABL-limited, probability
of success decreased. Results indicate that ABL resistance can bias Kt and Ki
estimates from overexpression systems, where the extent of bias is determined by
transporter expression level and substrate affinity.
PMID- 17038510
TI - Inhibition of human preadipocyte proteasomal activity by HIV protease inhibitors
or specific inhibitor lactacystin leads to a defect in adipogenesis, which
involves matrix metalloproteinase-9.
AB - In a previous publication, we reported that human immunodeficiency virus (HIV)
protease inhibitors (PIs) inhibited the differentiation of human preadipocytes in
primary culture, reducing the expression and secretion of matrix
metalloproteinase 9 (MMP-9). The present work was performed to clarify this
mechanism. Interestingly, HIV-PIs have been reported to be inhibitors of the
proteasome complex, which is known to regulate nuclear factor (NF)-kappaB
activation and transcription of its target genes, among them MMP-9. We thus
investigated the potential involvement of the proteasome in the antiadipogenic
effects of HIV-PIs. The effect of four HIV-PIs was tested on preadipocyte
proteasomal activity, and chronic treatment with the specific proteasome
inhibitor lactacystin was performed to evaluate alterations of adipogenesis and
MMP-9 expression/secretion. Finally, modifications of the NF-kappaB pathway
induced by either HIV-PIs or lactacystin were studied. We demonstrated that
preadipocyte proteasomal activity was decreased by several HIV-PIs and that
chronic treatment with lactacystin mimicked the effects of HIV-PIs by reducing
adipogenesis and MMP-9 expression/secretion. Furthermore, we observed an
intracellular accumulation of the NF-kappaB inhibitor, IkappaBbeta, with chronic
treatment with HIV-PIs or lactacystin as well as a decrease in MMP-9 expression
induced by acute tumor necrosis factor-alpha stimulation. These results indicate
that inhibition of the proteasome by specific (lactacystin) or nonspecific (HIV
PIs) inhibitors leads to a reduction of human adipogenesis, and they therefore
implicate deregulation of the NF-kappaB pathway and the related decrease of the
key adipogenic factor, MMP-9. This study adds significantly to recent reports
that have linked HIV-PI-related lipodystrophic syndrome with altered proteasome
function, endoplasmic reticulum stress, and metabolic disorders.
PMID- 17038511
TI - Desoxyrhaponticin (3,5-dihydroxy-4'-methoxystilbene 3-O-beta-D-glucoside)
inhibits glucose uptake in the intestine and kidney: In vitro and in vivo
studies.
AB - Rhubarb extracts have been reported to improve oral glucose tolerance in diabetic
animals. In the present study we have investigated the antidiabetic actions of
desoxyrhaponticin, a major stilbene in rhubarb, as a glucose uptake inhibitor.
Desoxyrhaponticin was demonstrated to inhibit glucose uptake in rabbit intestinal
membrane vesicles as well as in rat everted gut sleeves, with IC50 values of
148.3 and 30.9 microM, respectively. Kinetics studies revealed that
desoxyrhaponticin is a competitive inhibitor of glucose uptake in both systems.
Moreover, desoxyrhaponticin could reduce glucose uptake in the intestinal
membrane vesicles of both normal and diabetic rats. In addition, glucose uptake
in the renal membrane vesicles of both normal and diabetic rats was reduced by
desoxyrhaponticin. Under the inhibition of desoxyrhaponticin, uptake of glucose
in both the intestinal and renal membrane vesicles of the normal rats was no
different from that of the diabetic rats. The IC50 values of the uptake
inhibition in the renal membrane vesicles of normal and diabetic rats were 118.8
and 115.7 microM, respectively. In a type 2 diabetic animal model in which rats
have been treated with streptozotocin at the neonatal stage, postprandial
hyperglycemia was significantly suppressed by oral administration of this
compound (300 mg/kg b.wt.). These results suggest that desoxyrhaponticin is an
agent that is potentially effective in controlling postprandial hyperglycemia in
diabetes. The in vivo antidiabetic action of this compound can be explained, in
part at least, by inhibition of glucose transport in the small intestine and
inhibition of glucose reabsorption in the kidney.
PMID- 17038512
TI - WAY-163909 [(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta
[b][1,4]diazepino[6,7,1hi]indole]: A novel 5-hydroxytryptamine 2C receptor
selective agonist with preclinical antipsychotic-like activity.
AB - Serotonin-2C (5-HT2C) receptor antagonists and agonists have been shown to affect
dopamine (DA) neurotransmission, with agonists selectively decreasing mesolimbic
DA. As antipsychotic efficacy is proposed to be associated with decreased
mesolimbic DA neurotransmission by virtue of DA D2 receptor antagonism, the 5
HT2C-selective receptor agonist, WAY-163909 [(7bR,10aR)-1,2, 3,4,8,9,10,10a
octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7, 1hi]indole], was evaluated in
animal models of schizophrenia and in vivo microdialysis and electrophysiology to
determine the effects on mesolimbic and nigrostriatal DA neurotransmission.
Similar to clozapine, WAY-163909 (1.7-30 mg/kg i.p.) decreased apomorphine
induced climbing with little effect on stereotypy and no significant induction of
catalepsy. WAY-163909 (0.3-3 mg/kg s.c.) more potently reduced phencyclidine
induced locomotor activity compared with d-amphetamine with no effect on
spontaneous activity. WAY-163909 (1.7-17 mg/kg i.p.) reversed MK-801 (5H
dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate)- and DOI [1-(2,5
dimethoxy-4-iodophenyl)-2-aminopropane]-disrupted prepulse inhibition of startle
(PPI) and improved PPI in DBA/2N mice. In conditioned avoidance responding, WAY
163909 (0.3-3 mg/kg i.p.; 1-17 mg/kg p.o.) reduced avoidance responding, an
effect blocked by the 5-HT(2B/2C) receptor antagonist SB 206553 [5-methyl-1-(3
pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole]. WAY-163909 (10 mg/kg
s.c.) selectively decreased extracellular levels of DA in the nucleus accumbens
without affecting the striatum. Likewise, in vivo electrophysiological recordings
showed a decrease in the number of spontaneously firing DA neurons in the ventral
tegmental area but not in the substantia nigra with both acute and chronic (21
day) administration of WAY-163909 (1-10 mg/kg i.p.). Thus, the profile of the 5
HT2C selective receptor agonist WAY-163909 is similar to that of an atypical
antipsychotic and additionally may have rapid onset properties.
PMID- 17038513
TI - Repression of mesodermal fate by foxa, a key endoderm regulator of the sea urchin
embryo.
AB - The foxa gene is an integral component of the endoderm specification subcircuit
of the endomesoderm gene regulatory network in the Strongylocentrotus purpuratus
embryo. Its transcripts become confined to veg2, then veg1 endodermal
territories, and, following gastrulation, throughout the gut. It is also
expressed in the stomodeal ectoderm. gatae and otx genes provide input into the
pregastrular regulatory system of foxa, and Foxa represses its own transcription,
resulting in an oscillatory temporal expression profile. Here, we report three
separate essential functions of the foxa gene: it represses mesodermal fate in
the veg2 endomesoderm; it is required in postgastrular development for the
expression of gut-specific genes; and it is necessary for stomodaeum formation.
If its expression is reduced by a morpholino, more endomesoderm cells become
pigment and other mesenchymal cell types, less gut is specified, and the larva
has no mouth. Experiments in which blastomere transplantation is combined with
foxa MASO treatment demonstrate that, in the normal endoderm, a crucial role of
Foxa is to repress gcm expression in response to a Notch signal, and hence to
repress mesodermal fate. Chimeric recombination experiments in which veg2, veg1
or ectoderm cells contained foxa MASO show which region of foxa expression
controls each of the three functions. These experiments show that the foxa gene
is a component of three distinct embryonic gene regulatory networks.
PMID- 17038514
TI - The allantois and chorion, when isolated before circulation or chorio-allantoic
fusion, have hematopoietic potential.
AB - The chorio-allantoic placenta forms through the fusion of the allantois
(progenitor tissue of the umbilical cord), with the chorionic plate. The murine
placenta contains high levels of hematopoietic stem cells, and is therefore a
stem cell niche. However, it is not known whether the placenta is a site of
hematopoietic cell emergence, or whether hematopoietic cells originate from other
sites in the conceptus and then colonize the placenta. Here, we show that the
allantois and chorion, isolated prior to the establishment of circulation, have
the potential to give rise to myeloid and definitive erythroid cells following
explant culture. We further show that the hematopoietic potential of the
allantois and chorion does not require their union, indicating that it is an
intrinsic property of these tissues. These results suggest that the placenta is
not only a niche for, but also a source of, hematopoietic cells.
PMID- 17038515
TI - her5 expression reveals a pool of neural stem cells in the adult zebrafish
midbrain.
AB - Current models of vertebrate adult neural stem cells are largely restricted to
the rodent forebrain. To extract the general mechanisms of neural stem cell
biology, we sought to identify new adult stem cell populations, in other model
systems and/or brain areas. The teleost zebrafish appears to be an ideal system,
as cell proliferation in the adult zebrafish brain is found in many more niches
than in the mammalian brain. As a starting point towards identifying stem cell
populations in this system, we used an embryonic neural stem cell marker, the
E(spl) bHLH transcription factor Her5. We demonstrate that her5 expression is not
restricted to embryonic neural progenitors, but also defines in the adult
zebrafish brain a new proliferation zone at the junction between the mid- and
hindbrain. We show that adult her5-expressing cells proliferate slowly, self
renew and express neural stem cell markers. Finally, using in vivo lineage
tracing in her5:gfp transgenic animals, we demonstrate that the her5-positive
population is multipotent, giving rise in situ to differentiated neurons and glia
that populate the basal midbrain. Our findings conclusively identify a new
population of adult neural stem cells, as well as their fate and their endogenous
environment, in the intact vertebrate brain. This cell population, located
outside the forebrain, provides a powerful model to assess the general mechanisms
of vertebrate neural stem cell biology. In addition, the first transcription
factor characteristic of this cell population, Her5, points to the E(Spl) as a
promising family of candidate adult neural stem cell regulators.
PMID- 17038516
TI - LONGIFOLIA1 and LONGIFOLIA2, two homologous genes, regulate longitudinal cell
elongation in Arabidopsis.
AB - Plants have diversified their leaf morphologies to adapt to diverse ecological
niches. The molecular components responsible for regulating leaf morphology,
however, have not been fully elucidated. By screening Arabidopsis activation
tagging lines, we identified a dominant mutant, which we designated longifolia1
1D (lng1-1D). lng1-1D plants were characterized by long petioles, narrow but
extremely long leaf blades with serrated margins, elongated floral organs, and
elongated siliques. The elongated leaves of the mutant were due to increased
polar cell elongation rather than increased cell proliferation. Molecular
characterization revealed that this phenotype was caused by overexpression of the
novel gene LNG1, which was found to have a homolog, LNG2,in Arabidopsis. To
further examine the role of the LNG genes, we characterized lng1 and lng2 loss-of
function mutant lines. In contrast to the elongated leaves of lng1-1D plants, the
lng1 and lng2 mutants showed slightly decreased leaf length. Furthermore, the
lng1-3 lng2-1 double mutant showed further decreased leaf length associated with
less longitudinal polar cell elongation. The leaf widths in lng1-3 lng2-1 mutant
plants were similar to those in wild type, implying that the role of LNG1 and
LNG2 on polar cell elongation is similar to that of ROTUNDIFOLIA3 (ROT3).
However, analysis of a lng1-3 lng2-1 rot3-1 triple mutant and of a lng1-1D rot3-1
double mutant indicated that LNG1 and LNG2 promote longitudinal cell elongation
independently of ROT3. Taken together, these findings indicate that LNG1 and LNG2
are new components that regulate leaf morphology by positively promoting
longitudinal polar cell elongation independently of ROT3 in Arabidopsis.
PMID- 17038517
TI - Segment-specific requirements for dorsoventral patterning genes during early
brain development in Drosophila.
AB - An initial step in the development of the Drosophila central nervous system is
the delamination of a stereotype population of neural stem cells (neuroblasts,
NBs) from the neuroectoderm. Expression of the columnar genes ventral nervous
system defective (vnd), intermediate neuroblasts defective (ind) and muscle
segment homeobox (msh) subdivides the truncal neuroectoderm (primordium of the
ventral nerve cord) into a ventral, intermediate and dorsal longitudinal domain,
and has been shown to play a key role in the formation and/or specification of
corresponding NBs. In the procephalic neuroectoderm (pNE, primordium of the
brain), expression of columnar genes is highly complex and dynamic, and their
functions during brain development are still unknown. We have investigated the
role of these genes (with special emphasis on the Nkx2-type homeobox gene vnd) in
early embryonic development of the brain. We show at the level of individually
identified cells that vnd controls the formation of ventral brain NBs and is
required, and to some extent sufficient, for the specification of ventral and
intermediate pNE and deriving NBs. However, we uncovered significant differences
in the expression of and regulatory interactions between vnd, ind and msh among
brain segments, and in comparison to the ventral nerve cord. Whereas in the trunk
Vnd negatively regulates ind, Vnd does not repress ind (but does repress msh) in
the ventral pNE and NBs. Instead, in the deutocerebral region, Vnd is required
for the expression of ind. We also show that, in the anterior brain
(protocerebrum), normal production of early glial cells is independent from msh
and vnd, in contrast to the posterior brain (deuto- and tritocerebrum) and to the
ventral nerve cord.
PMID- 17038518
TI - The columnar gene vnd is required for tritocerebral neuromere formation during
embryonic brain development of Drosophila.
AB - In Drosophila, evolutionarily conserved transcription factors are required for
the specification of neural lineages along the anteroposterior and dorsoventral
axes, such as Hox genes for anteroposterior and columnar genes for dorsoventral
patterning. In this report, we analyse the role of the columnar patterning gene
ventral nervous system defective (vnd) in embryonic brain development. Expression
of vnd is observed in specific subsets of cells in all brain neuromeres. Loss-of
function analysis focussed on the tritocerebrum shows that inactivation of vnd
results in regionalized axonal patterning defects, which are comparable with the
brain phenotype caused by mutation of the Hox gene labial (lab). However, in
contrast to lab activity in specifying tritocerebral neuronal identity, vnd is
required for the formation and specification of tritocerebral neural lineages.
Thus, in early vnd mutant embryos, the Tv1-Tv5 neuroblasts, which normally
express lab, do not form. Later in embryogenesis, vnd mutants show an extensive
loss of lab-expressing cells because of increased apoptotic activity, resulting
in a gap-like brain phenotype that is characterized by an almost complete absence
of the tritocerebral neuromere. Correspondingly, genetic block of apoptosis in
vnd mutant embryos partially restores tritocerebral cells as well as axon tracts.
Taken together, our results indicate that vnd is required for the genesis and
proper identity specification of tritocerebral neural lineages during embryonic
brain development of Drosophila.
PMID- 17038519
TI - Nemo-like kinase (NLK) acts downstream of Notch/Delta signalling to downregulate
TCF during mesoderm induction in the sea urchin embryo.
AB - Studies in Caenorhabditis elegans and vertebrates have established that the MAP
kinase-related protein NLK counteracts Wnt signalling by downregulating the
transcription factor TCF. Here, we present evidence that during early development
of the sea urchin embryo, NLK is expressed in the mesodermal precursors in
response to Notch signalling and directs their fate by downregulating TCF. The
expression pattern of nlk is strikingly similar to that of Delta and the two
genes regulate the expression of each other. nlk overexpression, like ectopic
activation of Notch signalling, provoked massive formation of mesoderm and
associated epithelial mesenchymal transition. NLK function was found to be
redundant with that of the MAP kinase ERK during mesoderm formation and to
require the activity of the activating kinase TAK1. In addition, the sea urchin
NLK, like its vertebrate counterpart, antagonizes the activity of the
transcription factor TCF. Finally, activating the expression of a TCF-VP16
construct at blastula stages strongly inhibits endoderm and mesoderm formation,
indicating that while TCF activity is required early for launching the
endomesoderm gene regulatory network, it has to be downregulated at blastula
stage in the mesodermal lineage. Taken together, our results indicate that the
evolutionarily conserved TAK/NLK regulatory pathway has been recruited downstream
of the Notch/Delta pathway in the sea urchin to switch off TCF-beta-catenin
signalling in the mesodermal territory, allowing precursors of this germ layer to
segregate from the endomesoderm.
PMID- 17038520
TI - Phosphorylation of IP3R1 and the regulation of [Ca2+]i responses at
fertilization: a role for the MAP kinase pathway.
AB - A sperm-induced intracellular Ca2+ signal ([Ca2+]i) underlies the initiation of
embryo development in most species studied to date. The inositol 1,4,5
trisphosphate receptor type 1 (IP3R1) in mammals, or its homologue in other
species, is thought to mediate the majority of this Ca2+ release. IP3R1-mediated
Ca2+ release is regulated during oocyte maturation such that it reaches maximal
effectiveness at the time of fertilization, which, in mammalian eggs, occurs at
the metaphase stage of the second meiosis (MII). Consistent with this, the
[Ca2+]i oscillations associated with fertilization in these species occur most
prominently during the MII stage. In this study, we have examined the molecular
underpinnings of IP3R1 function in eggs. Using mouse and Xenopus eggs, we show
that IP3R1 is phosphorylated during both maturation and the first cell cycle at a
MPM2-detectable epitope(s), which is known to be a target of kinases controlling
the cell cycle. In vitro phosphorylation studies reveal that MAPK/ERK2, one of
the M-phase kinases, phosphorylates IP3R1 at at least one highly conserved site,
and that its mutation abrogates IP3R1 phosphorylation in this domain. Our studies
also found that activation of the MAPK/ERK pathway is required for the IP3R1 MPM2
reactivity observed in mouse eggs, and that eggs deprived of the MAPK/ERK pathway
during maturation fail to mount normal [Ca2+]i oscillations in response to
agonists and show compromised IP3R1 function. These findings identify IP3R1
phosphorylation by M-phase kinases as a regulatory mechanism of IP3R1 function in
eggs that serves to optimize [Ca2+]i release at fertilization.
PMID- 17038521
TI - Generation of GABAergic and dopaminergic interneurons from endogenous embryonic
olfactory bulb precursor cells.
AB - During the embryonic period, many olfactory bulb (OB) interneurons arise in the
lateral ganglionic eminence (LGE) from precursor cells expressing Dlx2, Gsh2 and
Er81 transcription factors. Whether GABAergic and dopaminergic interneurons are
also generated within the embryonic OB has not been studied thoroughly. In
contrast to abundant Dlx2 and Gsh2 expression in ganglionic eminences (GE), Dlx2
and Gsh2 proteins are not expressed in the E12.5-13.5 mouse OB, whereas the
telencephalic pallial domain marker Pax6 is abundant. We found GABAergic and
dopaminergic neurons originating from dividing precursor cells in E13.5 OB and in
short-term dissociated cultures prepared from the rostral half of E13.5 OB. In OB
cultures, 22% of neurons were GAD+, of which 53% were Dlx2+, whereas none
expressed Gsh2. By contrast, 70% of GAD+ cells in GE cultures were Dlx2+ and 16%
expressed Gsh2. In E13.5 OB slices transplanted with EGFP-labeled E13.5 OB
precursor cells, 31.7% of EGFP+ cells differentiated to GABAergic neurons. OB and
LGE precursors transplanted into early postnatal OB migrated and differentiated
in distinct patterns. Transplanted OB precursors gave rise to interneurons with
dendritic spines in close proximity to synaptophysin-positive boutons.
Interneurons were also abundant in differentiating OB neural stem cell cultures;
the neurons responded to the neurotrophin Bdnf and expressed presynaptic
proteins. In vivo, the Bdnf receptor TrkB colocalized with synaptic proteins at
the glomeruli. These findings suggest that, in addition to receiving interneurons
from the LGE, the embryonic OB contains molecularly distinct local precursor
cells that generate mature GABAergic and dopaminergic neurons.
PMID- 17038522
TI - Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro
and in vivo antitumor activities.
AB - Antigens expressed on malignant cells in the absence of significant expression on
normal tissues are highly desirable targets for therapeutic antibodies. CD70 is a
TNF superfamily member whose normal expression is highly restricted but is
aberrantly expressed in hematologic malignancies including non-Hodgkin lymphoma
(NHL), Hodgkin disease, and multiple myeloma. In addition, solid tumors such as
renal cell carcinoma, nasopharyngeal carcinoma, thymic carcinoma, meduloblastoma,
and glioblastoma express high levels of this antigen. To functionally target CD70
expressing cancers, a murine anti-CD70 monoclonal antibody was engineered to
contain human IgG1 constant domains. The engineered antibody retained the binding
specificity of the murine parent monoclonal antibody and was shown to induce Fc
mediated effector functions including antibody-dependent cellular cytotoxicity,
complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis
in vitro. Further, administration of this antibody significantly prolonged
survival of severe combined immunodeficient (SCID) mice bearing CD70+
disseminated human NHL xenografts. Survival of these mice was dependent upon the
activity of resident effector cells including neutrophils, macrophages, and
natural killer (NK) cells. These data suggest that an anti-CD70 antibody, when
engineered to contain human IgG1 constant domains, possesses effector cell
mediated antitumor activity and has potential utility for anticancer therapy.
PMID- 17038523
TI - Mad2 is required for optimal hematopoiesis: Mad2 associates with c-Kit in MO7e
cells.
AB - Mitotic arrest deficiency 2 (Mad2) is a component of mitotic spindle checkpoint
proteins and is essential for accurate chromosome segregation. We investigated a
role for Mad2 in hematopoiesis using Mad2-haploinsufficient (Mad2+/-) mice.
Mad2+/- bone marrow (BM) and spleen manifested decreased absolute numbers and
cycling status of immature, but not mature, hematopoietic progenitor cells.
Mad2+/- BM granulocyte-macrophage colony-forming units (CFU-GMs) did not manifest
synergistic proliferation in response to stem cell factor (SCF) plus GM-CSF. The
percentage of annexin V+ cells was higher in Mad2+/- than Mad2+/+c-Kit+lin- BM
after culture with SCF and GM-CSF. However, no significant difference in
phosphorylation of extracellular signal-related kinase (Erk1/2) at Thr202/Tyr204
and Akt at Ser473 between Mad2+/- and Mad2+/+BM c-Kit+lin- cells was observed.
Immunoprecipitation assays performed in human MO7e cells demonstrated physical
association of c-Kit with Mad2. Moreover, stimulation with SCF plus GM-CSF led to
dissociation of Mad2 from c-Kit. Confocal microscopy demonstrated that Mad2
colocalized with c-Kit in the cytoplasm of MO7e cells. These results suggest that
Mad2 is involved in synergistic growth of immature hematopoietic progenitor cells
in response to SCF plus GM-CSF, effects that may be mediated via physical
association of Mad2 with c-Kit.
PMID- 17038524
TI - The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human
B-cell lymphomas.
AB - We previously developed a multivariate model based on the RNA expression of 6
genes (LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2) that predicts survival in diffuse
large B-cell lymphoma (DLBCL) patients. Since LMO2 emerged as the strongest
predictor of superior outcome, we generated a monoclonal anti-LMO2 antibody in
order to study its tissue expression pattern. Immunohistologic analysis of over
1200 normal and neoplastic tissue and cell lines showed that LMO2 protein is
expressed as a nuclear marker in normal germinal-center (GC) B cells and GC
derived B-cell lines and in a subset of GC-derived B-cell lymphomas. LMO2 was
also expressed in erythroid and myeloid precursors and in megakaryocytes and also
in lymphoblastic and acute myeloid leukemias. It was rarely expressed in mature
T, natural killer (NK), and plasma cell neoplasms and was absent from
nonhematolymphoid tissues except for endothelial cells. Hierarchical cluster
analysis of immunohistologic data in DLBCL demonstrated that the expression
profile of the LMO2 protein was similar to that of other GC-associated proteins
(HGAL, BCL6, and CD10) but different from that of non-GC proteins (MUM1/IRF4 and
BCL2). Our results warrant inclusion of LMO2 in multivariate analyses to
construct a clinically applicable immunohistologic algorithm for predicting
survival in patients with DLBCL.
PMID- 17038525
TI - Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia.
AB - Bone marrow transplantation (BMT) is the only known cure for the hematologic
manifestations of Fanconi anemia (FA). Potential benefits of unrelated donor BMT
for FA, however, have been severely limited by graft rejection and treatment
related mortality with resultant poor survival. Therefore, we evaluated the
impact of potential prognostic factors on hematopoietic recovery, graft-versus
host disease (GVHD), and mortality in 98 recipients of unrelated donor BMT who
received transplants between 1990 and 2003. Probabilities of neutrophil (89% vs
69%; P = .02) and platelet (74% vs 23%; P < .001) recovery were higher after
fludarabine-containing regimens than nonfludarabine-containing regimens. Risks of
acute GVHD (relative risk [RR], 4.29; P < .001) were higher with non-T-cell
depleted grafts. The day-100 mortality rate was significantly higher after
nonfludarabine-containing regimens than fludarabine-containing regimens (65% vs
24%, respectively; P < .001). Corresponding 3-year adjusted overall survival
rates were 13% versus 52% (P < .001). In addition, mortality was higher in
recipients who were older (> 10 years), who were cytomegalovirus (CMV)
seropositive, and who received more than 20 blood product transfusions before
BMT. Based on these results, significant practice changes are suggested: use of a
fludarabine-containing conditioning regimen in the context of T-cell-depleted
marrow allografts, and earlier referral for transplantation prior to excessive
transfusions in patients with marrow failure.
PMID- 17038526
TI - Shear flow-dependent integration of apical and subendothelial chemokines in T
cell transmigration: implications for locomotion and the multistep paradigm.
AB - Lymphocyte extravasation requires that emigrating cells process chemoattractant
signals, typically mediated by chemokines, encountered on endothelial surface
(apical) and subendothelial (basal) compartments. These signals are delivered
under conditions of hemodynamic shear, a fundamental feature of all physiologic
leukocyte-endothelial interactions. To analyze lymphocyte responsiveness to
spatially distributed chemokines and their effects on transendothelial migration
(TEM) under hydrodynamic shear, we constructed a transwell-based flow assay. We
observed that the inflammatory chemokine CCL5 (RANTES) induces negligible human T
cell migration across inflamed human umbilical vascular endothelial cells
(HUVECs) when displayed alone in the subendothelial compartment under static or
hemodynamic shear conditions or when combined with apical CXCL12 (SDF-1alpha)
under static conditions. However, under shear stress, T cells encountering
apically presented CXCL12 were primed to undergo robust LFA-1-dependent TEM
toward subendothelial CCL5. Notably, locomotive T cells arriving at endothelial
junctions were retained and extended pseudopodia into and through the junctions,
thereby increasing sensitivity to subendothelial CCL5. These findings provide the
first evidence that lymphocytes integrate, conditional to shear forces,
permissive apical chemokine deposits, and integrin engagement signals, resulting
in morphologic changes and amplified chemotaxis to an otherwise weak
subendothelial chemokine signal.
PMID- 17038527
TI - The hypomorphic Gata1low mutation alters the proliferation/differentiation
potential of the common megakaryocytic-erythroid progenitor.
AB - Recent evidence suggests that mutations in the Gata1 gene may alter the
proliferation/differentiation potential of hemopoietic progenitors. By single
cell cloning and sequential replating experiments of prospectively isolated
progenitor cells, we demonstrate here that the hypomorphic Gata1low mutation
increases the proliferation potential of a unique class of progenitor cells,
similar in phenotype to adult common erythroid/megakaryocytic progenitors (MEPs),
but with the "unique" capacity to generate erythroblasts, megakaryocytes, and
mast cells in vitro. Conversely, progenitor cells phenotypically similar to mast
cell progenitors (MCPs) are not detectable in the marrow from these mutants. At
the single-cell level, about 11% of Gata1low progenitor cells, including MEPs,
generate cells that will continue to proliferate in cultures for up to 4 months.
In agreement with these results, trilineage (erythroid, megakaryocytic, and
mastocytic) cell lines are consistently isolated from bone marrow and spleen
cells of Gata1low mice. These results confirm the crucial role played by Gata1 in
hematopoietic commitment and identify, as a new target for the Gata1 action, the
restriction point at which common myeloid progenitors become either MEPs or MCPs.
PMID- 17038528
TI - Contribution of Toll-like receptors to the innate immune response to Gram
negative and Gram-positive bacteria.
AB - Innate recognition of bacteria is a key step in the activation of inflammation
and coagulation, and it is dependent on pathogen-associated molecular pattern
(PAMP) ligation to Toll-like receptors (TLRs) and CD14. The dominant receptors
activated when cells encounter a whole bacterium, which express several PAMPs,
are poorly defined. Herein, we have stimulated various human cells with
prototypic Gram-negative and Gram-positive bacteria. Receptor-dependent responses
to whole bacteria were assessed using both TLR-transfected cells and specific
monoclonal antibodies against TLRs, MD-2, and CD14. Enterobacteria-activated
leukocytes and endothelial cells in a TLR4/MD-2-dependent manner, most likely via
lipopolysaccharide (LPS). TLR2 activation was observed with a high bacterial
inoculum, and in epithelial cells expressing TLR2 but not TLR4. Pseudomonas
aeruginosa stimulated cells by both TLR2 and TLR4/MD-2. Gram-positive bacteria
activated cells only at high concentrations, in a partially TLR2-dependent but
TLR4/MD-2-independent manner. Either TLR or CD14 neutralization blocked
activation to all bacterial strains tested with the exception of some Gram
positive strains in whole blood in which partial inhibition was noted. This study
identifies dominant TLRs involved in responses to whole bacteria. It also
validates the concept that host cell activation by bacterial pathogens can be
therapeutically reduced by anti-TLR4, -TLR2, and -CD14 mAbs.
PMID- 17038529
TI - ZAP-70 enhances B-cell-receptor signaling despite absent or inefficient tyrosine
kinase activation in chronic lymphocytic leukemia and lymphoma B cells.
AB - Expression of ZAP-70 is an important negative prognostic factor in chronic
lymphocytic leukemia (CLL). This protein tyrosine kinase is a key mediator of T
cell receptor (TCR) signaling and is structurally homologous to Syk, which plays
an analogous role in B-cell receptor (BCR) signaling. Recent studies indicate
that ZAP-70 may participate in BCR signaling as well, but the mechanism of action
is not completely understood. We have now compared antigen receptor-induced
activation of ZAP-70 in B cells and T cells by analyzing phosphorylation of
critical regulatory tyrosine residues. We show that BCR-mediated activation of
ZAP-70 is very inefficient in CLL and lymphoma B cells and is negligible when
compared to activation of Syk. Despite the inefficient catalytic activation, the
ability of ZAP-70 to recruit downstream signaling molecules in response to
antigen receptor stimulation appeared relatively preserved. Moreover, ectopic
expression of ZAP-70 enhanced and prolonged activation of several key mediators
of BCR signaling, such as the Syk, ERK, and Akt kinases, and decreased the rate
of ligand-mediated BCR internalization. We conclude that the role of ZAP-70 in
BCR signaling is quite distinct from its role in TCR signaling and is likely
mediated by inhibition of events that terminate the signaling response.
PMID- 17038530
TI - Toll-like receptors and their ligands control mesenchymal stem cell functions.
AB - Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be
involved in tissue maintenance and repair as well as in the regulation of
hematopoiesis and immunologic responses. Thus, it is important to discover the
factors controlling MSC renewal and differentiation. Here we report that adult
MSCs express functional Toll-like receptors (TLRs), confirmed by the responses of
MSCs to TLR ligands. Pam3Cys, a prototypic TLR-2 ligand, augmented interleukin-6
secretion by MSC, induced nuclear factor kappa B (NF-kappaB) translocation,
reduced MSC basal motility, and increased MSC proliferation. The hallmark of MSC
function is the capacity to differentiate into several mesodermal lineages. We
show herein that Pam3Cys inhibited MSC differentiation into osteogenic,
adipogenic, and chondrogenic cells while sparing their immunosuppressive effect.
Our study therefore shows that a TLR ligand can antagonize MSC differentiation
triggered by exogenous mediators and consequently maintains the cells in an
undifferentiated and proliferating state in vitro. Moreover, MSCs derived from
myeloid factor 88 (MyD88)-deficient mice lacked the capacity to differentiate
effectively into osteogenic and chondrogenic cells. It appears that TLRs and
their ligands can serve as regulators of MSC proliferation and differentiation
and might affect the maintenance of MSC multipotency.
PMID- 17038531
TI - Donor antibodies to HNA-3a implicated in TRALI reactions prime neutrophils and
cause PMN-mediated damage to human pulmonary microvascular endothelial cells in a
two-event in vitro model.
AB - Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion
related mortality. Antibodies to HNA-3a are commonly implicated in TRALI. We
hypothesized that HNA-3a antibodies prime neutrophils (PMNs) and cause PMN
mediated cytotoxicity through a two-event pathogenesis. Isolated HNA-3a+ or HNA
3a- PMNs were incubated with plasma containing HNA-3a antibodies implicated in
TRALI, and their ability to prime the oxidase was measured. Human pulmonary
microvascular endothelial cells (HMVECs) were activated with endotoxin or buffer,
HNA-3a+ or HNA-3a- PMNs were added, and the coculture was incubated with plasma+/
antibodies to HNA-3a. PMN-mediated damage was measured by counting viable
HMVECs/mm2. Plasma containing HNA-3a antibodies primed the fMLP-activated
respiratory burst of HNA-3a+, but not HNA-3a-, PMNs and elicited PMN-mediated
damage of LPS-activated HMVECs when HNA-3a+, but not HNA-3a-, PMNs were used.
Thus, antibodies to HNA-3a primed PMNs and caused PMN-mediated HMVEC cytotoxicity
in a two-event model identical to biologic response modifiers implicated in
TRALI.
PMID- 17038532
TI - Receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) increases
vascular permeability: impaired permeability and angiogenesis in eNOS-deficient
mice.
AB - Receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) is emerging as an
important regulator of vascular pathophysiology. Here, we demonstrate a novel
role of RANKL as a vascular permeability factor and a critical role of
endothelial nitric oxide synthase (eNOS) in RANKL-induced endothelial function.
RANKL increased the vascular permeability and leukocyte infiltration in vivo and
caused the breakdown of the blood-retinal barrier in wild-type mice but not in
eNOS-deficient mice. In vitro, it increased endothelial permeability and reduced
VE-cadherin-facilitated endothelial cell-cell junctions in a NO-dependent manner.
RANKL also led to the activation of Akt and eNOS and to NO production in
endothelial cells (ECs). These effects were suppressed by the inhibition of
TRAF6, phosphoinositide 3'-kinase (PI3K), Akt, or NOS by genetic or pharmacologic
means. Inhibition of the TRAF6-mediated NO pathway reduced EC migration and
capillary-like tube formation in response to RANKL. Moreover, the effects of
RANKL on ECs sprouting from the aorta, and neovessel formation in both the mouse
Matrigel plug assay and corneal micropocket assay, were impaired in eNOS
deficient mice. These results demonstrate that RANKL promotes vascular
permeability and angiogenesis by stimulating eNOS by a TRAF6-PI3K-Akt-dependent
mechanism. These properties may be relevant to the pathogenesis of angiogenesis
dependent and inflammatory vascular diseases.
PMID- 17038533
TI - Prospective feasibility analysis of reduced-intensity conditioning (RIC) regimens
for hematopoietic stem cell transplantation (HSCT) in elderly patients with acute
myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).
AB - To prospectively assess the applicability of reduced-intensity conditioning
hematopoietic stem cell transplantation (RIC-HSCT), we wrote a protocol in which
all untreated patients 50 years or older with acute myeloid leukemia (AML) and
unfavorable cytogenetics would be evaluated during induction for a possible RIC
HSCT in first complete remission (CR1). Ninety-nine of 259 patients entered CR.
Fifty-three of the 99 were seen by the Transplant Service with the remainder not
seen because of illness, lack/unavailability of siblings, refusal, or, primarily,
unclear reasons (21 patients). A donor was identified for 26 patients (21
sibling, 5 unrelated) with RIC-HSCT performed in 14 (13 sibling). Results in
consulted patients suggested that 50% or fewer of the 85 patients who did not
undergo transplantation were potential transplant candidates. We attempted to
find one or more chemotherapy pair-mates for each patient who underwent
transplantation based on cytogenetics, age, and a relapse-free survival (RFS)
time that was more than or equal to the time from CR1 to RIC-HSCT in the patient
who underwent transplantation. Thirty-two of the 39 matches favored (longer RFS)
RIC-HSCT and 7, chemotherapy. The probability that the corresponding beta
distribution was different than expected (ie, that RIC-HSCT was superior) was
0.99 (P=.004). Results were similar with respect to survival. While RIC-HSCT thus
seems of interest, methods are needed to extend its applicability.
PMID- 17038534
TI - Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic
lymphocytic leukemia cells correlates with survival capacity.
AB - The gradual accumulation of chronic lymphocytic leukemia (B-CLL) cells is
presumed to derive from proliferation centers in lymph nodes and bone marrow. To
what extent these cells possess the purported antiapoptotic phenotype of
peripheral B-CLL cells is unknown. Recently, we have described that, in B-CLL
samples from peripheral blood, aberrant apoptosis gene expression was not limited
to protective changes but also included increased levels of proapoptotic BH3-only
member Noxa. Here, we compare apoptosis gene profiles from peripheral blood B-CLL
(n=15) with lymph node B-CLL (>90% CD5+/CD19+/CD23+ lymphocytes with Ki67+
centers; n=9). Apart from expected differences in Survivin and Bcl-xL, a
prominent distinction with peripheral B-CLL cells was the decreased averaged
level of Noxa in lymph nodes. Mcl-1 protein expression showed a reverse trend.
Noxa expression could be reduced also in vitro by CD40 stimulation of peripheral
blood B-CLL. Direct manipulation of Noxa protein levels was achieved by
proteasome inhibition in B-CLL and via RNAi in model cell lines. In each
instance, cell viability was directly linked with Noxa levels. These data
indicate that suppression of Noxa in the lymph node environment contributes to
the persistence of B-CLL at these sites and suggest that therapeutic targeting of
Noxa might be beneficial.
PMID- 17038535
TI - Production of interferons by dendritic cells, plasmacytoid cells, natural killer
cells, and interferon-producing killer dendritic cells.
AB - The capacity of mouse spleen conventional dendritic cells (cDCs) and plasmacytoid
dendritic cells (pDCs) to produce interferon-gamma (IFN-gamma) or IFN-alpha was
assessed, and compared with that of natural killer (NK) cells and the recently
identified interferon-producing killer dendritic cells (IKDCs), both of which are
frequent contaminants in DC preparations. Fully developed cDCs or pDCs, if free
of NK cells or IKDCs, showed little capacity for IFN-gamma production. However,
an early developmental form of the CD4-8+ cDC subtype, and the Ly6C- Ly49Q- pDC
subtype, both were able to produce moderate amounts of IFN-gamma, although less
than IKDCs. In response to toll-like receptor 9 stimuli, both the Ly6C+ Ly49Q+
and the Ly6C- Ly49Q- pDC subtypes were effective producers of IFN-alpha. However,
IKDCs, which efficiently produced IFN-gamma and showed immediate cytotoxicity on
NK target cells, did not produce IFN-alpha under these conditions.
PMID- 17038536
TI - Comparative single-institute analysis of cord blood transplantation from
unrelated donors with bone marrow or peripheral blood stem-cell transplants from
related donors in adult patients with hematologic malignancies after
myeloablative conditioning regimen.
AB - We studied the clinical outcomes of 171 adults with hematologic malignancies who
received unrelated cord blood transplantation (CBT) as a primary unrelated stem
cell source (n=100), or bone marrow transplant (BMT) or peripheral blood stem
cell transplant (PBSCT) from related donors (n=71, 55 BMT and 16 PBSCT). All
patients received myeloablative regimens including 12 Gy total body irradiation.
We analyzed the hematologic recovery, and risks of graft-versus-host disease
(GVHD), transplantation-related mortality (TRM) and relapse, and disease-free
survival (DFS) using Cox proportional hazards models. Significant delays in
engraftment occurred after cord blood transplantation; however, overall
engraftment rates were almost the same for both grafts. The cumulative incidences
of grades III to IV acute and extensive-type chronic GVHDs among CBT recipients
were significantly lower than those among BMT/PBSCT recipients. Multivariate
analysis demonstrated no apparent differences in TRM (9% in CBT and 13% in
BMT/PBSCT recipients), relapse (17% in CBT and 26% in BMT/PBSCT recipients), and
DFS (70% in CBT and 60% in BMT/PBSCT recipients) between both groups. These data
suggest that unrelated cord blood could be as safe and effective a stem-cell
source as related bone marrow or mobilized peripheral blood for adult patients
when it is used as a primary unrelated stem-cell source.
PMID- 17038537
TI - Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans, and
activation of this pathway is defective in HIV patients.
AB - An important mechanism of host defense to Cryptococcus neoformans involves the
direct microbicidal activity of lymphocytes. The importance of CD4+ T cells is
illustrated by the incidence of this infection in the acquired immunodeficiency
syndrome (AIDS) patients; however, the relative activity of microbicidal CD4+ T
cells compared with CD8+ T cells and natural killer (NK) cells has not been
established. Further, although NK cells and CD8+ T cells use perforin or
granulysin, respectively, to kill C neoformans, the effector molecule used by
CD4+ T cells is not known. Experiments demonstrated that IL-2-activated
peripheral blood lymphocytes from healthy adults acquire anticryptococcal
activity, and surprisingly, that CD4+ T cells had the most profound effect on
this activity. Using SrCl(2)induced degranulation and siRNA knockdown, granulysin
was shown to be the effector molecule. Although activation by anti-CD3 + IL-2
resulted in the additional expression of perforin, this did not improve the
anticryptococcal activity. Cryptococcal killing by CD4+ T cells was defective in
human immunodeficiency virus (HIV)-infected patients due to dysregulated
granulysin and perforin production in response to IL-2 or anti-CD3 + IL-2. In
conclusion, CD4+ T cells are the major subset of cells responsible for killing C
neoformans in peripheral blood. These cells use granulysin as the effector
molecule, and priming is dysregulated in HIV-infected patients, which results in
defective microbicidal activity.
PMID- 17038538
TI - Dissecting the role of endothelial SURVIVIN DeltaEx3 in angiogenesis.
AB - The identification of alternative splice variants of Survivin that possess
distinct functions from those originally identified for the main Survivin isoform
has greatly increased the complexity of our understanding of the role of Survivin
in different cells. Previous functional studies of the Survivin splice variants
have been performed almost exclusively in cancer cells. However, Survivin has
increasingly been implicated in other normal physiologic and pathophysiologic
processes, including angiogenesis. In this study, we dissect the involvement of
Survivin DeltaEx3 in angiogenesis. We show by confocal microscopy that a pool of
endothelial Survivin DeltaEx3 is localized to membrane ruffles. We also
demonstrate that Survivin DeltaEx3 is the Survivin splice variant responsible for
modulating angiogenesis in vitro, in tube formation assays, and in vivo, in an in
vivo angiogenesis assay. Our data indicate that Survivin DeltaEx3 may regulate
angiogenesis via several mechanisms including cell invasion, migration, and Rac1
activation. Our findings identify a novel pathway regulating angiogenesis through
Survivin DeltaEx3 and a novel mechanism for Rac1 activation during angiogenesis.
In conclusion, our results provide new insights into the regulation of
endothelial cell homeostasis and angiogenesis by the Survivin proteins.
PMID- 17038539
TI - Constitutive activation of Stat5 promotes its cytoplasmic localization and
association with PI3-kinase in myeloid leukemias.
AB - Persistent activation of Stat5 is frequently found in hematologic neoplasms.
Studies conducted with constitutively active Stat5 mutants (Stat51*6 and cS5F)
have shown that deregulated Stat5 activity promotes leukemogenesis. To
investigate the oncogenic properties of these mutants, we used cS5F-expressing
bone marrow cells which induce a multilineage leukemia when transplanted into
recipient mice. Here, we show by immunocytochemistry that cS5F is localized
mainly in the cytoplasmic compartment of leukemic cells, suggesting that the
transforming nature of cS5F may be associated with a cytoplasmic function. In
support of this hypothesis, we found that cS5F forms a complex with the p85
subunit of the phosphatidylinositol 3-kinase (PI3-K) and the scaffolding adapter
Gab2 in leukemic bone marrow cells, resulting in the activation of Akt/PKB, a
crucial downstream target of PI3-K. By using transducible TAT-Gab2 or TAT-Akt
recombinant proteins, we were able to demonstrate that activation of the PI3
kinase/Akt pathway by cS5F molecules through Gab2 is essential for induction of
cell growth. We also found that persistently phosphorylated Stat5 in primary
cells from patients with myeloid leukemias has a cytoplasmic localization. These
data suggest that oncogenic Stat5 proteins exert dual transforming capabilities
not only as transcriptional activators but also as cytoplasmic signaling
effectors.
PMID- 17038540
TI - The spindle checkpoint.
PMID- 17038541
TI - Microtubule nucleation: gamma-tubulin and beyond.
AB - Centrosomes and their fungal equivalents, spindle pole bodies (SPBs), are the
main microtubule (MT)-organizing centers in eukaryotic cells. Several proteins
have been implicated in microtubule formation by centrosomes and SPBs, including
microtubule-minus-end-binding proteins and proteins that bind along the length or
stabilize the plus ends of microtubules. Recent work has improved our
understanding of the molecular mechanisms of MT formation. In particular, it has
shown that gamma-tubulin and its associated proteins play key roles in
microtubule nucleation and spindle assembly in evolutionarily distant species
ranging from fungi to mammals. Other work indicates that gamma-tubulin-mediated
microtubule nucleation, although necessary, is not sufficient for mitotic spindle
assembly but requires additional proteins that regulate microtubule nucleation
independently of centrosomes.
PMID- 17038542
TI - Generation of noncentrosomal microtubule arrays.
AB - In most proliferating and migrating animal cells, the centrosome is the main site
for microtubule (MT) nucleation and anchoring, leading to the formation of radial
MT arrays in which MT minus ends are anchored at the centrosomes and plus ends
extend to the cell periphery. By contrast, in most differentiated animal cell
types, including muscle, epithelial and neuronal cells, as well as most fungi and
vascular plant cells, MTs are arranged in noncentrosomal arrays that are non
radial. Recent studies suggest that these noncentrosomal MT arrays are generated
by a three step process. The initial step involves formation of noncentrosomal
MTs by distinct mechanisms depending on cell type: release from the centrosome,
catalyzed nucleation at noncentrosomal sites or breakage of pre-existing MTs. The
second step involves transport by MT motor proteins or treadmilling to sites of
assembly. In the final step, the noncentrosomal MTs are rearranged into cell-type
specific arrays by bundling and/or capture at cortical sites, during which MTs
acquire stability. Despite their relative stability, the final noncentrosomal MT
arrays may still exhibit dynamic properties and in many cases can be remodeled.
PMID- 17038543
TI - The synapsin domain E accelerates the exoendocytotic cycle of synaptic vesicles
in cerebellar Purkinje cells.
AB - Synapsins are synaptic-vesicle-associated phosphoproteins implicated in the
regulation of neurotransmitter release and excitability of neuronal networks.
Mutation of synapsin genes in mouse and human causes epilepsy. To understand the
role of the highly conserved synapsin domain E in the dynamics of release from
mammalian inhibitory neurons, we generated mice that selectively overexpress the
most conserved part of this domain in cerebellar Purkinje cells. At Purkinje-cell
nuclear-neuron synapses, transgenic mice were more resistant to depression
induced by short or prolonged high-frequency stimulations. The increased synaptic
performance was accompanied by accelerated release kinetics and shorter synaptic
delay. Despite a marked decrease in the total number of synaptic vesicles,
vesicles at the active zone were preserved or slightly increased. The data
indicate that synapsin domain E increases synaptic efficiency by accelerating
both the kinetics of exocytosis and the rate of synaptic vesicle cycling and
decreasing depression at the inhibitory Purkinje-cell-nuclear-neuron synapse.
These effects may increase the sensitivity of postsynaptic neurons to inhibition
and thereby contribute to the inhibitory control of network activity.
PMID- 17038544
TI - Increased Rheb-TOR signaling enhances sensitivity of the whole organism to
oxidative stress.
AB - The accumulation of free radical damage to an organism over its lifespan can
cause premature aging and disease including cancer, atherosclerosis and
neurodegenerative disorders. The well-conserved Rheb-Target-of-rapamycin (TOR)-S6
kinase (S6K) signaling pathway regulates several cellular processes and has been
shown to influence lifespan and diseases such as cancer and neurodegenerative
disorders. Using adult Drosophila, we describe for the first time in metazoans
that TOR activity can influence the stress response. We find that mildly
increasing systemic Rheb-TOR-S6K signaling sensitizes the whole organism to
oxidative stress and promotes senescence of locomotor activity with age.
Furthermore, we find that S6K is required for increased Rheb-TOR signaling to
sensitize the whole organism to oxidative stress and promote the senescence of
locomotor activity. Interestingly, we also find that increasing Rheb-TOR
signaling in muscle can increase the sensitivity of adults to oxidative stress.
These data imply that pathological situations that increase TOR activity might
perturb the ability of the whole organism to cope with stress causing disease
progression and aging.
PMID- 17038545
TI - HDAC activity regulates entry of mesoderm cells into the cardiac muscle lineage.
AB - Class II histone deacetylases (HDAC4, HDAC5, HDAC7 and HDAC9) have been shown to
interact with myocyte enhancer factors 2 (MEF2s) and play an important role in
the repression of cardiac hypertrophy. We examined the role of HDACs during the
differentiation of P19 embryonic carcinoma stem cells into cardiomyocytes.
Treatment of aggregated P19 cells with the HDAC inhibitor trichostatin A induced
the entry of mesodermal cells into the cardiac muscle lineage, shown by the
upregulation of transcripts Nkx2-5, MEF2C, GATA4 and cardiac alpha-actin.
Furthermore, the overexpression of HDAC4 inhibited cardiomyogenesis, shown by the
downregulation of cardiac muscle gene expression. Class II HDAC activity is
inhibited through phosphorylation by Ca2+/calmodulin-dependent kinase (CaMK).
Expression of an activated CaMKIV in P19 cells upregulated the expression of Nkx2
5, GATA4 and MEF2C, enhanced cardiac muscle development, and activated a MEF2
responsive promoter. Moreover, inhibition of CaMK signaling downregulated GATA4
expression. Finally, P19 cells constitutively expressing a dominant-negative form
of MEF2C, capable of binding class II HDACs, underwent cardiomyogenesis more
efficiently than control cells, implying the relief of an inhibitor. Our results
suggest that HDAC activity regulates the specification of mesoderm cells into
cardiomyoblasts by inhibiting the expression of GATA4 and Nkx2-5 in a stem cell
model system.
PMID- 17038546
TI - Targeted homozygous deletion of M-band titin in cardiomyocytes prevents sarcomere
formation.
AB - Titin, a multifunctional protein that stretches from the Z-disk to the M-band in
heart and skeletal muscle, contains a kinase domain, phosphorylation sites and
multiple binding sites for structural and signalling proteins in the M-band. To
determine whether this region is crucial for normal sarcomere development, we
created mouse embryonic stem cell (ES) lines in which either one or both alleles
contained a targeted deletion of the entire M-band-coding region, leaving Z-disk
binding and myosin-filament-binding sites intact. ES cells were differentiated
into cardiomyocytes, and myofibrillogenesis investigated by immunofluorescence
microscopy. Surprisingly, deletion of one allele did not markedly affect
differentiation into cardiomyocytes, suggesting that a single intact copy of the
titin gene is sufficient for normal myofibrillogenesis. By contrast, deletion of
both alleles resulted in a failure of differentiation beyond an early stage of
myofibrillogenesis. Sarcomeric myosin remained in non-striated structures, Z-disk
proteins, such as alpha-actinin, were mainly found in primitive dot-like
structures on actin stress fibres, M-band-associated proteins (myomesin,
obscurin, Nbr1, p62 and MURF2) remained punctate. These results show that
integration of the M-band region of titin is required for myosin filament
assembly, M-band formation and maturation of the Z-disk.
PMID- 17038547
TI - A role for non-muscle myosin II function in furrow maturation in the early
zebrafish embryo.
AB - Cytokinesis in early zebrafish embryos involves coordinated changes in the f
actin- and microtubule-based cytoskeleton, and the recruitment of adhesion
junction components to the furrow. We show that exposure to inhibitors of non
muscle myosin II function does not affect furrow ingression during the early
cleavage cycles but interferes with the recruitment of pericleavage f-actin and
cortical beta-catenin aggregates to the furrow, as well as the remodeling of the
furrow microtubule array. This remodeling is in turn required for the distal
aggregation of the zebrafish germ plasm. Embryos with reduced myosin activity
also exhibit at late stages of cytokinesis a stabilized contractile ring
apparatus that appears as a ladder-like pattern of short f-actin cables,
supporting a role for myosin function in the disassembly of the contractile ring
after furrow formation. Our studies support a role for myosin function in furrow
maturation that is independent of furrow ingression and which is essential for
the recruitment of furrow components and the remodeling of the cytoskeleton
during cytokinesis.
PMID- 17038549
TI - Isolated autosomal dominant growth hormone deficiency: stimulating mutant GH-1
gene expression drives GH-1 splice-site selection, cell proliferation, and
apoptosis.
AB - The majority of mutations that cause isolated GH deficiency type II (IGHD II)
affect splicing of GH-1 transcripts and produce a dominant-negative GH isoform
lacking exon 3 resulting in a 17.5-kDa isoform, which further leads to disruption
of the GH secretory pathway. A clinical variability in the severity of the IGHD
II phenotype depending on the GH-1 gene alteration has been reported, and in
vitro and transgenic animal data suggest that the onset and severity of the
phenotype relates to the proportion of 17.5-kDa produced. The removal of GH in
IGHD creates a positive feedback loop driving more GH expression, which may
itself increase 17.5-kDa isoform productions from alternate splice sites in the
mutated GH-1 allele. In this study, we aimed to test this idea by comparing the
impact of stimulated expression by glucocorticoids on the production of different
GH isoforms from wild-type (wt) and mutant GH-1 genes, relying on the
glucocorticoid regulatory element within intron 1 in the GH-1 gene. AtT-20 cells
were transfected with wt-GH or mutated GH-1 variants (5'IVS-3 + 2-bp T->C; 5'IVS
3 + 6 bp T->C; ISEm1: IVS-3 + 28 G->A) known to cause clinical IGHD II of varying
severity. Cells were stimulated with 1 and 10 mum dexamethasone (DEX) for 24 h,
after which the relative amounts of GH-1 splice variants were determined by
semiquantitative and quantitative (TaqMan) RT-PCR. In the absence of DEX, only
around 1% wt-GH-1 transcripts were the 17.5-kDa isoform, whereas the three mutant
GH-1 variants produced 29, 39, and 78% of the 17.5-kDa isoform. DEX stimulated
total GH-1 gene transcription from all constructs. Notably, however, DEX
increased the amount of 17.5-kDa GH isoform relative to the 22- and 20-kDa
isoforms produced from the mutated GH-1 variants, but not from wt-GH-1. This DEX
induced enhancement of 17.5-kDa GH isoform production, up to 100% in the most
severe case, was completely blocked by the addition of RU486. In other studies,
we measured cell proliferation rates, annexin V staining, and DNA fragmentation
in cells transfected with the same GH-1 constructs. The results showed that that
the 5'IVS-3 + 2-bp GH-1 gene mutation had a more severe impact on those measures
than the splice site mutations within 5'IVS-3 + 6 bp or ISE +28, in line with the
clinical severity observed with these mutations. Our findings that the proportion
of 17.5-kDa produced from mutant GH-1 alleles increases with increased drive for
gene expression may help to explain the variable onset progression, and severity
observed in IGHD II.
PMID- 17038548
TI - Scavenging of 14-3-3 proteins reveals their involvement in the cell-surface
transport of ATP-sensitive K+ channels.
AB - Arginine (Arg)-based endoplasmic reticulum (ER)-localization signals are involved
in the quality control of different heteromultimeric membrane protein complexes.
ATP-sensitive potassium (KATP) channels are unique because each subunit in the
heterooctamer contains an Arg-based ER-localization signal. We have dissected the
inactivation events that override the ER-localization activity of the eight
peptide-sorting motifs. Employing a 14-3-3-scavenger construct to lower the
availability of 14-3-3 proteins, we found that 14-3-3 proteins promote the cell
surface expression of heterologously expressed and native KATP channels. 14-3-3
proteins were detected in physical association with KATP channels in a pancreatic
beta-cell line. Our results suggest that the Arg-based signal present in Kir6.2
is sterically masked by the SUR1 subunit. By contrast, 14-3-3 proteins
functionally antagonized the Arg-based signal present in SUR1. The last ten amino
acids were required for efficient 14-3-3 recruitment to multimeric forms of the
Kir6.2 C-terminus. Channels containing a pore-forming subunit lacking these
residues reached the cell surface inefficiently but were functionally
indistinguishable from channels formed by the full-length subunits. In
conclusion, 14-3-3 proteins promote the cell-surface transport of correctly
assembled complexes but do not regulate the activity of KATP channels at the cell
surface.
PMID- 17038550
TI - Arsenite modulates cardiac substrate preference by translocation of GLUT4, but
not CD36, independent of mitogen-activated protein kinase signaling.
AB - The protein thiol-modifying agent arsenite, a potent activator of stress
signaling, was used to examine the involvement of MAPKs in the regulation of
cardiac substrate uptake. Arsenite strongly induced p38 MAPK phosphorylation in
isolated rat cardiac myocytes but also moderately enhanced phosphorylation of
p42/44 ERK and p70 S6K. At the level of cardiomyocytic substrate use, arsenite
enhanced glucose uptake dose dependently up to 5.1-fold but failed to stimulate
long-chain fatty acid uptake. At the substrate transporter level, arsenite
stimulated the translocation of GLUT4 to the sarcolemma but failed to recruit
CD36 or FABPpm. Because arsenite did not influence the intrinsic activity of
glucose transporters, GLUT4 translocation is entirely responsible for the
selective increase in glucose uptake by arsenite. Moreover, the nonadditivity of
arsenite-induced glucose uptake and insulin-induced glucose uptake indicates that
arsenite recruits GLUT4 from insulin-responsive intracellular stores. Inhibitor
studies with SB203580/SB202190, PD98059, and rapamycin indicate that activation
of p38 MAPK, p42/44 ERK, and p70 S6K, respectively, are not involved in arsenite
induced glucose uptake. In addition, all these kinases do not play a role in
regulation of cardiac glucose and long-chain fatty acid uptake by insulin. Hence,
arsenite's selective stimulation of glucose uptake appears unrelated to its
signaling actions, suggesting that arsenite acts via thiol modification of a
putative intracellular protein target of arsenite within insulin-responsive GLUT4
containing stores. Because of arsenite's selective stimulation of cardiac glucose
uptake, identification of this putative target of arsenite within the GLUT4
storage compartment may indicate whether it is a target for future strategies in
prevention of diabetic cardiomyopathy.
PMID- 17038552
TI - Regulation of pituitary cell function by adiponectin.
AB - Adiponectin is a member of the family of adipose tissue-related hormones known as
adipokines, which exerts antidiabetic, antiatherogenic, antiinflammatory, and
antiangiogenic properties. Adiponectin actions are primarily mediated through
binding to two receptors expressed in several tissues, AdipoR1 and AdipoR2.
Likewise, adiponectin expression has been detected in adipocytes as well as in a
variety of extra-adipose tissues, including the chicken pituitary. Interestingly,
adiponectin secretion and adiponectin receptor expression in adipocytes have been
shown to be regulated by pituitary hormones. These observations led us to
investigate whether adiponectin, like the adipokine leptin, regulates pituitary
hormone production. Specifically, we focused our analysis on somatotrophs and
gonadotrophs because of the relationship between the control of energy
metabolism, growth and reproduction. To this end, the effects of adiponectin on
both GH and LH secretion as well as its interaction with major stimulatory
regulators of somatotrophs (ghrelin and GHRH) and gonadotrophs (GnRH) and with
their corresponding receptors (GHS-R, GHRH-R, and GnRH-R), were evaluated in rat
pituitary cell cultures. Results show that adiponectin inhibits GH and LH release
as well as both ghrelin-induced GH release and GnRH-stimulated LH secretion in
short-term (4 h) treated cell cultures, wherein the adipokine also increases GHRH
R and GHS-R mRNA content while decreasing that of GnRH-R. Additionally, we
demonstrate that the pituitary expresses both adiponectin and adiponectin
receptors under the regulation of the adipokine. In sum, our data indicate that
adiponectin, either locally produced or from other sources, may play a
neuroendocrine role in the control of both somatotrophs and gonadotrophs.
PMID- 17038551
TI - Estrogen decrease in tight junctional resistance involves matrix
metalloproteinase-7-mediated remodeling of occludin.
AB - Estrogen modulates tight junctional resistance through estrogen receptor-alpha
mediated remodeling of occludin. The objective of the study was to understand the
mechanisms involved. Experiments using human normal vaginal-cervical epithelial
cells showed that human normal vaginal-cervical epithelial cells secrete
constitutively matrix-metalloproteinase-7 (MMP-7) into the luminal solution and
that MMP-7 is necessary and sufficient to produce estrogen decrease of tight
junctional resistance and remodeling of occludin. Treatment with estrogen
stimulated activation of the pro-MMP-7 intracellularly and augmented secretion of
the activated MMP-7 form. Steady-state levels of MMP-7 mRNA and protein were not
affected by estrogen. Estrogen modulated phosphorylation of the MMP-7, but the
changes were most likely secondary to changes in cellular MMP-7 mass. Estrogen
increased coimmunoreactivity of MMP-7 with the Golgi protein GPP130. Tunicamycin
and brefeldin-A had no effect on cellular MMP-7 but monensin (inhibitor of Golgi
traffic) blocked estrogen effects, suggesting estrogen site of action is at the
Golgi system. Estrogen increased generalized secretory activity, including of
luminal exocytosis of polycarbohydrates. However, estrogen increased
coimmunoreactivity of MMP-7 with synaptosomal-associated protein of 25 kDa in
apical membranes, suggesting soluble N-ethylmaleimide sensitive fusion factor
attachment protein receptor-facilitated exocytosis of MMP-7. Treatment with the
vesicular-ATPase inhibitor bafilomycin A(1) inhibited activation of MMP-7. These
data suggest that estrogen up-regulates activation of the MMP-7 intracellularly,
at the level of Golgi, and augments secretion of activated MMP-7 through soluble
N-ethylmaleimide sensitive fusion factor attachment protein receptor-dependent
exocytosis. On the other hand, estrogen acidification of the luminal solution
would tend to alkalinize exocytotic vesicles and may lead to decreased activation
of the MMP-7. These mechanisms acting in concert could be important for
regulation and control of estrogen modulation of paracellular permeability in
vivo.
PMID- 17038553
TI - The inhibitory effect of leptin on angiotensin II-induced vasoconstriction in
vascular smooth muscle cells is mediated via a nitric oxide-dependent mechanism.
AB - Leptin inhibits the contractile response induced by angiotensin (Ang) II in
vascular smooth muscle cells (VSMCs) of the aorta. We studied in vitro and ex
vivo the role of nitric oxide (NO) in the effect of leptin on the Ang II-induced
vasoconstriction of the aorta of 10-wk-old Wistar rats. NO and nitric oxide
synthase (NOS) activity were assessed by the Griess and (3)H-arginine/citrulline
conversion assays, respectively. Stimulation of inducible NOS (iNOS) as well as
Janus kinases/signal transducers and activators of transcription (JAK/STAT) and
phosphoinositide 3-kinase (PI3K)/Akt signaling pathways were determined by
Western blot. The contractile responses to Ang II were evaluated in endothelium
denuded aortic rings using the organ bath system. Changes in intracellular Ca(2+)
were measured in VSMCs using fura-2 fluorescence. Leptin significantly (P < or =
0.01) stimulated NO release and NOS activity in VSMCs. Leptin's effect on NO was
abolished by the NOS inhibitor, N(G)-monomethyl l-arginine, or the iNOS selective
inhibitor L-N(6)-(1-iminoethyl)-lysine. Accordingly, leptin increased iNOS
protein expression, with a comparable time course with that of NO production and
NOS activity. Leptin also significantly increased STAT3 (P < or = 0.01) and Akt
(P < or = 0.001) phosphorylation. Moreover, either the JAK2 inhibitor, AG490, or
the PI3K inhibitor, wortmannin, significantly (P < or = 0.05) abrogated the
leptin-induced increase in iNOS protein. Finally, both N(G)-monomethyl L-arginine
and L-N(6)-(1-iminoethyl)-lysine inhibitors completely blunted (P < or = 0.001)
the leptin-mediated inhibition of the Ang II-induced VSMC activation and
vasoconstriction. These findings suggest that the endothelium-independent
depressor action of leptin is mediated by an increase of NO bioavailability in
VSMCs. This process requires the up-regulation of iNOS through mechanisms
involving JAK2/STAT3 and PI3K/Akt pathways.
PMID- 17038554
TI - A novel mutation in the bone morphogenetic protein 15 gene causing defective
protein secretion is associated with both increased ovulation rate and sterility
in Lacaune sheep.
AB - Genetic mutations with major effects on ovulation rate and litter size in sheep
were recently identified in three genes belonging to the TGFbeta superfamily
pathway: the bone morphogenetic protein 15 (BMP15, also known as GDF9b), growth
differentiation factor 9 (GDF9), and BMP receptor type IB (also known as activin
like kinase 6). Homozygous BMP15 or GDF9 mutations raise female sterility due to
a failure of normal ovarian follicle development, whereas heterozygous animals
for BMP15 or GDF9 as well as heterozygous and homozygous animals for BMP receptor
type IB show increased ovulation rates. In the present work, a new naturally
occurring mutation in the BMP15 gene in the high prolific Lacaune sheep breed is
described. The identified variant is a C53Y missense nonconservative substitution
leading to the aminoacidic change of a cysteine with a tyrosine in the mature
peptide of the protein. As for other mutations found in the same gene, this is
associated with an increased ovulation rate and sterility in heterozygous and
homozygous animals, respectively. Further in vitro studies showed that the C53Y
mutation was responsible for the impairment of the maturation process of the
BMP15 protein, resulting in a defective secretion of both the precursor and
mature peptide. Overall, our findings confirm the essential role of the BMP15
factor in the ovarian folliculogenesis and control of ovulation rate in sheep.
PMID- 17038555
TI - Tumor necrosis factor-alpha regulates steroidogenesis, apoptosis, and cell
viability in the human adrenocortical cell line NCI-H295R.
AB - TNF-alpha regulates the hypothalamo-pituitary-adrenal axis at several levels. It
has been shown to modify adrenal steroidogenesis in many species, and it is
supposed to act as an auto/paracrine factor. However, its significance in human
adrenocortical function remains unclear. Therefore, we investigated the effect of
TNF-alpha on adrenal steroidogenesis, expression of the key steroidogenic genes,
apoptosis, and cell viability in the human adrenocortical cell line NCI-H295R.
TNF-alpha treatment (1 nM for 48 h) decreased the basal production of cortisol,
androstenedione, dehydroepiandrosterone sulfate (DHEAS), and aldosterone (14, 18,
35, and 52%, respectively), and the 8-bromo-cAMP-induced production of cortisol,
androstenedione, dehydroepiandrosterone (DHEA), and DHEAS (44, 66, 58, and 48%,
respectively). However, when the steroid production data were normalized by the
cell number, TNF-alpha increased the basal production of cortisol,
androstenedione, DHEA, DHEAS, and aldosterone (137, 121, 165, 73, and 28%,
respectively), and the 8-bromo-cAMP-induced production of cortisol, DHEAS, and
aldosterone (122, 121, and 256%, respectively). This was accompanied by a
parallel increase in the expression of the genes encoding for the steroidogenic
acute regulatory protein, 3beta-hydroxysteroid dehydrogenase 2, and 17
hydroxylase/17,20-lyase (74, 200, and 50%, respectively; quantitative real-time
RT-PCR analysis). TNF-alpha increased caspase 3/7 activity (an indicator of
apoptosis) and decreased cell viability dose and time dependently. The effect of
TNF-alpha on apoptosis was neutralized by a monoclonal TNF-alpha antibody. These
findings indicate that TNF-alpha is a potent regulator of steroidogenesis and
cell viability in adrenocortical cells. TNF-alpha may have physiological and/or
pathophysiological significance as an endocrine and/or paracrine/autocrine
regulator of adrenocortical function.
PMID- 17038556
TI - Interleukin-1beta-induced insulin resistance in adipocytes through down
regulation of insulin receptor substrate-1 expression.
AB - Inflammation is associated with obesity and insulin resistance. Proinflammatory
cytokines produced by adipose tissue in obesity could alter insulin signaling and
action. Recent studies have shown a relationship between IL-1beta level and
metabolic syndrome or type 2 diabetes. However, the ability of IL-1beta to alter
insulin signaling and action remains to be explored. We demonstrated that IL
1beta slightly increased Glut 1 translocation and basal glucose uptake in 3T3-L1
adipocytes. Importantly, we found that prolonged IL-1beta treatment reduced the
insulin-induced glucose uptake, whereas an acute treatment had no effect. Chronic
treatment with IL-1beta slightly decreased the expression of Glut 4 and markedly
inhibited its translocation to the plasma membrane in response to insulin. This
inhibitory effect was due to a decrease in the amount of insulin receptor
substrate (IRS)-1 but not IRS-2 expression in both 3T3-L1 and human adipocytes.
The decrease in IRS-1 amount resulted in a reduction in its tyrosine
phosphorylation and the alteration of insulin-induced protein kinase B activation
and AS160 phosphorylation. Pharmacological inhibition of ERK totally inhibited IL
1beta-induced down-regulation of IRS-1 mRNA. Moreover, IRS-1 protein expression
and insulin-induced protein kinase B activation, AS160 phosphorylation, and Glut
4 translocation were partially recovered after treatment with the ERK inhibitor.
These results demonstrate that IL-1beta reduces IRS-1 expression at a
transcriptional level through a mechanism that is ERK dependent and at a
posttranscriptional level independently of ERK activation. By targeting IRS-1, IL
1beta is capable of impairing insulin signaling and action, and could thus
participate in concert with other cytokines, in the development of insulin
resistance in adipocytes.
PMID- 17038557
TI - Increased hypothalamic protein tyrosine phosphatase 1B contributes to leptin
resistance with age.
AB - Animals at advanced ages exhibit a reduction in central leptin sensitivity.
However, changes in growth, metabolism, and obesity risk occur much earlier in
life, particularly during the transition from youth to middle age. To determine
when initial decreases in central leptin sensitivity occur, leptin-dependent
suppression of food intake was tested in 8-, 12-, and 20-wk-old male, chow-fed
Sprague Dawley rats. Intracerebroventricular leptin injection (3 microg)
suppressed 24-h food intake in 8- and 12-wk-old rats (P < 0.05) but not 20-wk-old
rats. To identify potential cellular mediators of this resistance, we focused on
protein tyrosine phosphatase 1B (PTP1B), a recently described inhibitor of leptin
signaling. PTP1B protein levels, as determined by Western blot, were
significantly higher in mediobasal hypothalamic punches collected from 20-wk-old
rats, compared with 8-wk-old rats (P < 0.05). When 20-wk-old rats were fasted for
24 h, levels of hypothalamic PTP1B decreased (P < 0.05), coincident with a
restoration of leptin sensitivity. To directly test whether inhibition of PTP1B
restores leptin sensitivity, 20-wk-old chow-fed rats were pretreated with a
pharmacological PTP1B inhibitor 1 h before leptin, and 24-h food intake was
recorded. As expected, leptin alone produced a small but nonsignificant reduction
in food intake. However, pretreatment with the PTP1B inhibitor resulted in a
marked improvement in leptin-dependent suppression of food intake (P < 0.05).
These data are consistent with the hypothesis that increases in PTP1B contribute
to hypothalamic leptin resistance as rats transition into middle age.
PMID- 17038558
TI - Severity of the catabolic condition differentially modulates hypothalamic
expression of growth hormone-releasing hormone in the fasted mouse: potential
role of neuropeptide Y and corticotropin-releasing hormone.
AB - To determine whether the severity of the catabolic condition differentially
regulates the GH axis, male mice were either fed ad libitum or fasted for 12, 24,
and 48 h. Hypothalami, pituitaries, and stomachs were collected for assessment of
mRNA levels by quantitative real-time RT-PCR, and blood collected for measurement
of plasma hormone and metabolite levels by commercial assay kits. Overnight (12
h) fasting resulted in a significant suppression of circulating glucose, insulin,
IGF-I, and leptin levels and an increase in corticosterone, free fatty acids, and
n-octanoyl ghrelin levels, and these directional changes were maintained at the
24- and 48-h time points. Fasting (24 h) also increased circulating GH levels,
which was associated with an increase in pituitary mRNA levels for GHRH receptor
and ghrelin receptor and a decrease in mRNA levels for somatostatin (SST)
receptor (SSTR) subtypes, SSTR2, SSTR3, and SSTR5, where the changes in ghrelin
receptor and SSTR expression persisted after 48 h fasting. Hypothalamic SST mRNA
levels were not altered by fasting, whereas there was a transient rise in stomach
SST mRNA levels 24 h after food withdrawal. In contrast, there was a biphasic
effect of fasting on GHRH expression. GHRH mRNA levels were significantly
elevated at 12 and 24 h but fell to approximately 50% of fed controls 48 h after
food withdrawal. A sequential rise in hypothalamic neuropeptide Y (NPY) and CRH
mRNA levels preceded the fall in GHRH expression, where fasting-induced changes
in CRH and GHRH mRNA levels were not observed in 48-h-fasted NPY knockout mice.
These observations, in light of previous reports showing both NPY and CRH can
inhibit GHRH expression and GH release, suggest that these neuronal systems may
work in concert to control the ultimate impact of fasting on GH axis function.
PMID- 17038559
TI - Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy.
AB - Glucocorticoids mediate muscle atrophy in many catabolic states. Myostatin
expression, a negative regulator of muscle growth, is increased by
glucocorticoids and myostatin overexpression is associated with lower muscle
mass. This suggests that myostatin is required for the catabolic effects of
glucocorticoids. We therefore investigated whether myostatin gene disruption
could prevent muscle atrophy caused by glucocorticoids. Male myostatin knockout
(KO) and wild-type mice were subjected to dexamethasone treatment (1 mg/kg.d for
10 d or 5 mg/kg.d for 4 d). In wild-type mice, daily administration of low-dose
dexamethasone for 10 d resulted in muscle atrophy (tibialis anterior: -15%;
gastrocnemius: -13%; P < 0.01) due to 15% decrease in the muscle fiber cross
sectional area (1621 +/- 31 vs. 1918 +/- 64 microm(2), P < 0.01). In KO mice,
there was no reduction of muscle mass nor fiber cross-sectional area after
dexamethasone treatment. Muscle atrophy after 4 d of high-dose dexamethasone was
associated with increased mRNA of enzymes involved in proteolytic pathways
(atrogin-1, muscle ring finger 1, and cathepsin L) and increased chymotrypsin
like proteasomal activity. In contrast, the mRNA of these enzymes and the
proteasomal activity were not significantly affected by dexamethasone in KO mice.
Muscle IGF-I mRNA was paradoxically decreased in KO mice (-35%, P < 0.05); this
was associated with a potentially compensatory increase of IGF-II expression in
both saline and dexamethasone-treated KO mice (2-fold, P < 0.01). In conclusion,
our results show that myostatin deletion prevents muscle atrophy in
glucocorticoid-treated mice, by blunting the glucocorticoid-induced enhanced
proteolysis, and suggest an important role of myostatin in muscle atrophy caused
by glucocorticoids.
PMID- 17038560
TI - Reversal of glucocorticoids-dependent proopiomelanocortin gene inhibition by
leukemia inhibitory factor.
AB - We previously have described molecular mechanisms converging at the Nur response
element-signal transducer and activator of transcription (STAT) composite site
responsible for synergistic activation of the proopiomelanocortin (POMC) gene
promoter by leukemia inhibitory factor (LIF) and CRH. In this study, we asked how
glucocorticoids (GC), the physiological negative regulators of POMC gene
expression, modulate this synergism. In the corticotroph cell line AtT-20, the
response of the wild-type promoter to LIF+CRH was barely inhibited by GC, whereas
a distal promoter subregion (-414/-293) encompassing the Nur response element
STAT site and devoid of the negative GC-responsive element located in the
proximal domain, displayed a cooperative response to LIF+dexamethasone (DEX) and
LIF+CRH+DEX treatments. LIF+CRH-stimulated ACTH secretion was also inefficiently
inhibited by DEX in the same cell line. This study was focused thereafter on
LIF+DEX cooperativity, which may be responsible, on the wild-type promoter, for
lack of negative regulation by DEX of the LIF+CRH synergy. The STAT1-3 low
affinity site, in the context of the (-414/-293) subregion of the POMC promoter,
was found necessary and sufficient for transcriptional synergism between
activated GC receptor (GR) and STAT1-3. Moreover the activities of reporters
specific for STAT1-3 or GR were reciprocally enhanced by DEX or LIF. Single and
sequential chromatin immunoprecipitations revealed 1) a STAT-dependent
corecruitment of coactivators after LIF and LIF+DEX stimulation and 2) a more
lasting recruitment of both STAT3 and GR in the same enhanceosome on the
endogenous POMC promoter after LIF+DEX joint stimulation than after the single
one. Such events may be responsible for a lack of repressive property of GR
unmasked on the whole POMC promoter during LIF+CRH stimulation and may contribute
to the tonicity of the hypothalamic-pituitary-adrenal axis during inflammatory
infectious diseases.
PMID- 17038561
TI - Apoptosis of rat granulosa cells after staurosporine and serum withdrawal is
suppressed by adenovirus-directed overexpression of prohibitin.
AB - Prohibitin (Phb1) is a highly conserved mitochondrial protein that is associated
with granulosa cell differentiation, atresia, and luteolysis. Although prohibitin
has been implicated in the suppression of apoptosis in mammalian cells, its
specific role in programmed cell death in granulosa cells is unknown. In the
present study, we examined the role of prohibitin in mediating staurosporine
(STS) and serum withdrawal induced apoptosis in undifferentiated rat granulosa
cells. Treatment of granulosa cells isolated from immature rat ovaries with STS
and/or serum withdrawal induced a rapid decrease in the transmembrane potential
of mitochondria, resulting in increased prohibitin content and induced apoptosis
in a time- and dose-dependent manner. Infection of granulosa cells with a Phb1
adenoviral construct resulted in overexpression of prohibitin that markedly
attenuated the ability of STS and serum withdrawal to induce apoptosis via the
intrinsic apoptotic pathway. To determine the site of action of Phb1, granulosa
cells were transfected with a prohibitin-eGFP fusion construct, and the fusion
protein expression patterns were analyzed by fluorescence microscopy and Western
blot analysis of cell fractionated samples. These studies indicated that the
prohibitin-eGFP fusion protein moved from the cytoplasm into the mitochondria.
However, no prohibitin-eGFP fusion protein was observed in the nucleus in
response to the STS-induced apoptotic stimulus. This result was corroborated by
Western blot analysis with green fluorescent protein-specific antibody.
Furthermore, the prohibitin-eGFP fusion protein also inhibited programmed cell
death. These results provide evidence that prohibitin could serve an
antiapoptotic role in undifferentiated granulosa cells.
PMID- 17038563
TI - Contrasting evolution of expression differences in the testis between species and
subspecies of the house mouse.
AB - Regulatory changes in genes involved in reproduction are thought to be prime
targets for divergence during speciation, since they are expected to play an
important role in sexual selection and sexual conflict. We used microarray
analysis of RNA from different wild populations of house mouse subspecies
(including Mus m. musculus, Mus m. domesticus, and Mus m. castaneus) and from the
sister species Mus spretus to test this assumption. A comparison of expression
divergence in brain, liver/kidney, and testis shows a major difference in the
evolutionary dynamics of testis-related genes. While the comparison between
species confirms an excess in divergence in testis genes, we find that all
comparisons between subspecies yield only a very small number of genes with
significantly different expression levels in the testis. These results suggest
that the early phase of the speciation process may not be driven by regulatory
changes in genes that are potential targets of sexual selection, and that the
divergence in these genes is only established during a later phase of the
speciation process.
PMID- 17038564
TI - Flexibility and constraint in the nucleosome core landscape of Caenorhabditis
elegans chromatin.
AB - Nucleosome positions within the chromatin landscape are known to serve as a major
determinant of DNA accessibility to transcription factors and other interacting
components. To delineate nucleosomal patterns in a model genetic organism,
Caenorhabditis elegans, we have carried out a genome-wide analysis in which DNA
fragments corresponding to nucleosome cores were liberated using an enzyme
(micrococcal nuclease) with a strong preference for cleavage in non-nucleosomal
regions. Sequence analysis of 284,091 putative nucleosome cores obtained in this
manner from a mixed-stage population of C. elegans reveals a combined picture of
flexibility and constraint in nucleosome positioning. As has previously been
observed in studies of individual loci in diverse biological systems, we observe
areas in the genome where nucleosomes can adopt a wide variety of positions in a
given region, areas with little or no nucleosome coverage, and areas where
nucleosomes reproducibly adopt a specific positional pattern. In addition to
illuminating numerous aspects of chromatin structure for C. elegans, this
analysis provides a reference from which to begin an investigation of
relationships between the nucleosomal pattern, chromosomal architecture, and
lineage-based gene activity on a genome-wide scale.
PMID- 17038568
TI - Current trends in the management of iatrogenic cervical carotid artery injuries.
AB - This study was undertaken to elicit the opinion of experts regarding the
management of iatrogenic injury to the carotid artery. A text questionnaire was
transmitted by electronic mail to members of the Western Vascular Society
concerning management of iatrogenic injury to the cervical carotid artery.
Participants were asked to submit information regarding practice status and their
preferred choices for the management of different clinical scenarios. The
scenarios were: (1) large bore sheath (> 8.5F) cannulation of the carotid artery
in anesthetized patients, (2) large bore sheath cannulation of the carotid artery
in an awake patient, (3) delayed recognition of a misplaced sheath by > 4 hours,
and (4) arterial puncture was recognized after only the entry needle (16-gauge)
was introduced but before sheath insertion. Finally, the members were asked to
comment on the management of abnormal findings on duplex scanning, such as
intimal flap or pseudoaneurysm. A response rate of 42% was obtained (45/106
active members). Eighty-two percent of respondents had been in practice for
longer than 10 years. Eighty-nine percent had seen this complication and 29% had
cared for patients in whom subsequent neurologic deficit developed. The
institutional incidence of such injury was 1-5 cases per year for 82% of
respondents. Sixteen-gauge needle injury was managed by immediate removal and
applied pressure by 98% of respondents. When large-bore sheath injury is
recognized within 1 hour of insertion, 62% of respondents would remove the sheath
and hold pressure, with or without obtaining a duplex ultrasound examination.
However, if injury recognition was delayed for > 4 hours, 82% would proceed to
surgery. Only 26% operated on asymptomatic carotid flap found on ultrasound,
while the remaining 74% would base their decision on size and flow
characteristics on ultrasound. The management of pseudoaneurysm differed
significantly. Whereas 31% of respondents would manage this finding expectantly,
69% would proceed to surgery regardless of size or symptoms. Despite awareness of
iatrogenic injury to the cervical carotid artery, the institutional incidence
remains high. Two thirds of respondents would manage a misplaced sheath in the
carotid artery nonoperatively if the injury was recognized immediately. However,
if injury recognition was delayed for > 4 hours, the majority of respondents
would remove the sheath surgically. While the management of intimal flap largely
depended on size and flow characteristics, 69% of respondents would operate on a
pseudoaneurysm regardless of size or symptoms. The results of this survey may
serve as a guideline for the management of this potentially devastating injury.
PMID- 17038569
TI - Critical limb ischemia in the dialysis-dependent patient: infrainguinal vein
bypass is justified.
AB - The combination of critical limb ischemia and end-stage renal failure (ESRF, ie,
dialysis- dependent) represents severe systemic atherosclerosis and is associated
with a very poor medium-term survival. Many nephrologists and surgeons advocate
primary amputation. We examined the recent experience in this unit to determine
whether infrainguinal bypass in these patients can be justified. Retrospective
study of all patients with critical limb ischemia and ESRF undergoing surgery in
a regional vascular and renal unit between January 1996 and May 2003. Forty-two
patients with ESRF (median age 65 years) were referred with critical limb
ischemia. Seventeen patients underwent 24 (7 bilateral) infrainguinal bypasses
(17 autologous vein, 7 polytetrafluoroethylene [PTFE] conduit; tissue loss in
21/24, 88%), and 25 patients had primary major amputations of 32 limbs. Early
occlusion occurred in 5 grafts (21%, all 5/5 PTFE). In-hospital mortality was 13%
in the bypass group, 24% in the amputation group. Median in-hospital stay was 59
days in the bypass group, 46 days in the amputation group. Thirty-day, 1- and 2
year survival was 88%, 50%, and 33% in the bypass group; 83%, 39%, and 35% in the
amputation group. The limb salvage rate was 66% at 1 year. Seventy-five percent
(18/24) of operated on limbs (15/17 of vein grafts) avoided major amputation at
follow-up (median 18 months) or death. The combination of critical limb ischemia
and end- stage renal failure carries a poor medium-term survival independent of
primary amputation or surgical revascularization. Infrainguinal bypass in
selected cases with vein conduit can, however, allow the majority of these
patients to avoid major limb amputation.
PMID- 17038566
TI - Experimental validation of predicted mammalian erythroid cis-regulatory modules.
AB - Multiple alignments of genome sequences are helpful guides to functional
analysis, but predicting cis-regulatory modules (CRMs) accurately from such
alignments remains an elusive goal. We predict CRMs for mammalian genes expressed
in red blood cells by combining two properties gleaned from aligned, noncoding
genome sequences: a positive regulatory potential (RP) score, which detects
similarity to patterns in alignments distinctive for regulatory regions, and
conservation of a binding site motif for the essential erythroid transcription
factor GATA-1. Within eight target loci, we tested 75 noncoding segments by
reporter gene assays in transiently transfected human K562 cells and/or after
site-directed integration into murine erythroleukemia cells. Segments with a high
RP score and a conserved exact match to the binding site consensus are validated
at a good rate (50%-100%, with rates increasing at higher RP), whereas segments
with lower RP scores or nonconsensus binding motifs tend to be inactive. Active
DNA segments were shown to be occupied by GATA-1 protein by chromatin
immunoprecipitation, whereas sites predicted to be inactive were not occupied. We
verify four previously known erythroid CRMs and identify 28 novel ones. Thus,
high RP in combination with another feature of a CRM, such as a conserved
transcription factor binding site, is a good predictor of functional CRMs. Genome
wide predictions based on RP and a large set of well-defined transcription factor
binding sites are available through servers at http://www.bx.psu.edu/.
PMID- 17038565
TI - Human heterochromatin proteins form large domains containing KRAB-ZNF genes.
AB - Heterochromatin is important for gene regulation and chromosome structure, but
the genes that are occupied by heterochromatin proteins in the mammalian genome
are largely unknown. We have adapted the DamID method to systematically identify
target genes of the heterochromatin proteins HP1 and SUV39H1 in human and mouse
cells. Unexpectedly, we found that CBX1 (formerly HP1beta) and SUV39H1 bind to
genes encoding KRAB domain containing zinc finger (KRAB-ZNF) transcriptional
repressors. These genes constitute one of the largest gene families and are
organized in clusters in the human genome. Preference of CBX1 for this gene
family was observed in both human and mouse cells. High-resolution mapping on
human chromosome 19 revealed that CBX1 coats large domains 0.1-4 Mb in size,
which coincide with the position of KRAB-ZNF gene clusters. These domains show an
intricate CBX1 binding pattern: While CBX1 is globally elevated throughout the
domains, it is absent from the promoters and binds more strongly to the 3' ends
of KRAB-ZNF genes. KRAB-ZNF domains contain large numbers of LINE elements, which
may contribute to CBX1 recruitment. These results uncover a surprising link
between heterochromatin and a large family of regulatory genes in mammals. We
suggest a role for heterochromatin in the evolution of the KRAB-ZNF gene family.
PMID- 17038570
TI - Techniques for preserving vertebral artery perfusion during thoracic aortic stent
grafting requiring aortic arch landing.
AB - Thoracic endografting offers many advantages over open repair. However, delivery
of the device can be difficult and may necessitate adjunctive procedures. We
describe our techniques for preserving perfusion to the left subclavian artery
despite endograft coverage to obtain a proximal seal zone. We reviewed our
experience with the Talent thoracic stent graft (Medtronic, Santa Rosa, CA). From
1999 to 2003, 49 patients received this device (29 men, 20 women). Seventeen
patients required adjunctive procedures to facilitate proximal graft placement.
We performed left subclavian-to-left common carotid artery transposition (6),
left common carotid-to-left subclavian artery bypass with ligation proximal to
the vertebral artery (7), and left common carotid-to-left subclavian artery
bypass with proximal coil embolization (4). Patients who had anatomy unfavorable
to transposition or bypass with proximal ligation (large aneurysms or proximal
vertebral artery origin) were treated with coil embolization of the proximal left
subclavian artery in order to prevent subsequent type II endoleaks. Technical
success rate of the carotid subclavian bypass was 100%. Patient follow-up ranged
from 3 to 48 months with a mean of 12 months. Six patients had follow-up <6
months owing to recent graft placement. Primary patency was 100%. No neurologic
events occurred during the procedure or upon follow-up. One patient had a
transient chyle leak that spontaneously resolved in 24 hours. Another patient had
a phrenic nerve paresis that resolved after 3 weeks. We believe that it is
important to maintain patency of the vertebral artery specifically when a patent
right vertebral system and an intact basilar artery is not demonstrated.
Furthermore, we describe a novel technique of coil embolization of the proximal
left subclavian artery in conjunction with left common carotid-to-left subclavian
artery bypass. This circumvents the need for potentially hazardous mediastinal
dissection and ligation of the proximal left subclavian artery in cases of large
proximal aneurysms or unfavorable vertebral artery anatomy.
PMID- 17038571
TI - Evaluation of thrombogenicity by indium-111 platelet scintigraphy in endografting
for abdominal aortic aneurysms.
AB - Obstruction of the endograft limb by thrombosis has often been reported and may
cause fatal complications such as leg necrosis or myonephropathic metabolic
syndrome. The purpose of this study was to evaluate endograft antithrombogenicity
by indium-111 platelet scintigraphy. Seventeen patients with abdominal aortic
aneurysms were treated by endografting. Thirteen patients were treated with
conventional open surgery using an artificial graft. The endograft was
constructed from a self-expanding Z-shaped stent and woven polyester fabric.
Autologous platelets labeled with indium-111 were injected at 2 weeks
postoperatively. At 24 hours and 72 hours postinjection, the ratio of
scintillation count of the endograft or graft to that of the native artery was
calculated to assess platelet deposition. The normalization ratio was calculated
as follows: (scintillation count per pixel of endograft or
graft/circumference)/(scintillation count per pixel of the native femoral
artery). Platelet factor 4 and beta-thromboglobulin were measured to evaluate the
systemic platelets activity at 2 weeks postoperatively. There was no significant
difference in platelet counts or labeling efficiency between the groups. The
ratio was significantly higher in the endografting group than in the open surgery
group at 72 hours postinjection (2.5-0.7 vs 3.9-1.1, P<.001). There was no
significant difference in platelet factor 4 and beta-thromboglobulin between the
groups. Although there was no difference in systemic platelet activity,
endografting was associated with lower antithrombogenicity. It remains unclear
whether lower antithrombogenicity causes thromboembolism as a complication of the
procedure. The authors recommend the administration of antiplatelet drugs to
prevent endograft obstruction in patients with very narrow iliac arteries.
PMID- 17038572
TI - The Baltimore activity scale for intermittent claudication: a validation study.
AB - The purpose of this study was to develop and cross-validate the Baltimore
Activity Scale for Intermittent Claudication (BASIC) questionnaire in patients
with peripheral arterial disease limited by intermittent claudication, and to
determine whether the BASIC questionnaire score changed following a supervised
program of exercise rehabilitation. A total of 702 consecutive patients with
peripheral arterial disease and stable intermittent claudication were
characterized on physical activity level using the BASIC questionnaire and an
accelerometer. The first 351 patients tested were included in the validation
group, whereas the final 351 patients were included in the cross-validation
group. Subsequently, 61 of these patients participated in a randomized,
controlled trial in which 28 patients completed 6 months of exercise
rehabilitation and 24 patients completed usual care control. The sum of 5
questions from the BASIC questionnaire (0-10 point scale) was predictive of daily
physical activity using the following regression equation: Daily Physical
Activity (kcal/day) = 102.2 + (49.6 x BASIC score); R = 0.76, R(2) = 0.58,
standard error of estimate = 52.0 kcal/day, P < .0001. This equation was
successfully cross-validated on an independent group of patients, as the
predicted daily physical activity (339 - 181 kcal/day, mean - SD) was similar (P
= .501) to measured daily physical activity (347 - 266 kcal/day, mean - SD).
Furthermore, the BASIC score increased 38% following 6 months of exercise
rehabilitation (P < .01), whereas no change was observed in the control group (P
> .05). A composite of 5 questions obtained from the self-administered BASIC
questionnaire accurately estimates daily physical activity in patients with
peripheral arterial disease limited by intermittent claudication, and is
sensitive to change in physical activity following a program of exercise
rehabilitation.
PMID- 17038573
TI - Iron deficiency in the acute-phase reaction after open aortic surgery.
AB - The objective of this study was to quantify the magnitude of iron deficiency in
the postoperative period after open aortic surgery. This was a prospective
observational study in 55 consecutive patients. Blood samples were obtained on
postoperative days 1, 2, 4, 30, and 45, and the parameters determined were the
following: iron, transferrin, transferrin saturation index, transferrin-soluble
receptor, ferritin, red cell count, hemoglobin, hematocrit, serum C-reactive
protein, fibrinogen, mean corpuscular volume, mean corpuscular hemoglobin, mean
corpuscular hemoglobin concentration, and number of blood units transfused. We
performed statistical ANOVA test for repetitive measurements (lower bound) in
regard to its basal level. Iron deficiency and its parameters reached the maximum
at 48 hours postoperatively (iron: 18.92 g/dL and transferrin saturation index:
11.1%) (P <.05). There was not a complete recovery after 45 days (iron: 51.23
g/dL and transferrin saturation index: 18.0%) (P <.05). A similar evolution was
observed in the other measured parameters (red cell count: 3.5 x 106/L.;
hemoglobin: 10.4 g/dL; hematocrit: 30.7%) (P <.005), none affecting the values of
concentration or volume (P <.05). Transferrin-soluble receptors, normal at first,
were increased at postoperative days 30 and 45 (2.7 and 2.4 mg/dL respectively, P
<.005). After open aortic surgery there is an important acute-phase reaction, a
dramatic iron deficiency, and a lack of its transporters until the 45th analyzed
day. The elevation of transferrin-soluble receptors in the 4th and 6th weeks
denotes a necessity of iron supplementation for a correct development of the
immature hematic cells since blood parameters do not reach normal levels in the
6th postoperative week.
PMID- 17038574
TI - Techniques for managing complications of arterial closure devices.
AB - According to data reported by the American Heart Association, more than 5 million
diagnostic and therapeutic catheterizations are performed each year in the United
States. The number of catheterizations has tripled since 1979. It has been
estimated that complications related to the access site result in more than
75,000 surgical procedures annually. Thus, improved management of the access site
itself is essential to achieve the greater goals of improved care and reduced
cost. Manual compression directly over the site of arterial puncture usually
results in adequate hemostasis but has several significant drawbacks. Manual
compression is uncomfortable for the patient, is fatiguing and time-consuming for
staff, and necessitates several hours of costly in-hospital observation. In
addition, it may be ineffective in achieving hemostasis, especially in the
setting of systemic anticoagulation or following the use of large-bore devices.
Based on the perceived need for an improved method of managing the arterial
access site following catheterization, various vascular sealing devices have been
developed. There are at least 8 (and the number is increasing) hemostatic
vascular closure devices that are currently approved by the FDA for access site
closure after femoral arterial catheterization. The chief advantage attributed to
vascular sealing devices is accelerated access site hemostasis, even in the
setting of anticoagulation, leading to earlier ambulation and hospital discharge
following arterial catheterization. The most important drawbacks related to
vascular sealing devices include the cost of the devices and the possibility of
increased access site complications. Despite the paucity of properly designed
studies supporting their use, it is estimated that over one million vascular
sealing devices are used annually in the United States, a number that has
increased dramatically in the past 5 years.In this review, we present a brief
description of the design and function of the most widely used devices, describe
the most common mechanisms of failure, and recommend strategies for management of
access site complications including hemorrhage, arterial obstruction, and
infection.
PMID- 17038575
TI - Endovascular repair of a symptomatic subclavian artery aneurysm in a patient with
Marfan syndrome: a case report.
AB - Endovascular techniques are being employed with increasing frequency in the
management of peripheral arterial aneurysms. A 57-year-old patient with Marfan
syndrome presented with a symptomatic 5 cm left subclavian artery aneurysm. He
underwent successful endovascular exclusion of the aneurysm with immediate
improvement of his symptoms. Duplex ultrasound 3 months after the procedure
confirmed a patent graft and complete exclusion of the aneurysm.
PMID- 17038576
TI - Endovascular coil embolization for large femoral false aneurysms: two case
reports.
AB - Ultrasound-guided compression and thrombin injections are reliable for the
management of small and medium-sized false aneurysms. However, owing to technical
limitations, large false aneurysms often necessitate surgical intervention, which
is associated with significant postoperative morbidity and mortality.
Endovascular coil embolization is an evolving minimally invasive technique that
can be used as a safe option for large false femoral aneurysms. We report our
experience with 2 cases of large false femoral aneurysms treated by using coils
to occlude the aneurysm's feeding tract successfully.
PMID- 17038577
TI - Cerebrospinal fluid drainage in the treatment of spontaneous spinal cord
ischemia: a case report.
AB - A patient with spontaneous acute spinal cord ischemia successfully treated with
cerebrospinal fluid drainage is reported. There are no consensus guidelines on
the management of spinal cord ischemia. Various preventive and rehabilitative
measures have been suggested, but the best treatment remains unknown.
PMID- 17038578
TI - Left renal vein reconstruction after right nephrectomy and inadvertent left renal
vein ligation: a case report and review of the literature.
AB - Left renal vein ligation has been used as a technical aid to gain exposure to the
perirenal aorta and to control bleeding in abdominal aortic operations. Left
renal vein ligation is considered to be well tolerated in patients with 2
functioning kidneys, but has rarely been described in the setting of concomitant
right nephrectomy and presents a management challenge. Some reports suggest
recovery of renal function may be possible after left renal vein ligation during
right nephrectomy, but other suggest that a delay in revascularizing the left
renal venous drainage may result in irreversible nephropathy. This article
reports the inadvertent division of the left renal vein during right nephrectomy.
Renal failure ensued postoperatively. The left renal vein was reconstructed, and
renal function was recovered. The inability to reliably predict which patients
will have adverse outcome after left renal vein ligation in the setting of a
right nephrectomy may necessitate preemptive intervention.
PMID- 17038579
TI - Large uterine fibroids causing mechanical obstruction of the inferior vena cava
and subsequent thrombosis: a case report.
AB - A 35-year-old woman presented with severe left leg swelling and pain after a
spontaneous abortion of a 20-week fetus. Duplex ultrasound imaging confirmed
venous thrombosis of the left iliac, common femoral, superficial femoral, deep
femoral, greater saphenous, posterior tibial, and popliteal, peroneal, and soleal
veins. A computed tomography scan showed large uterine fibroids that were
completely compressing the distal inferior vena cava and both ureters, with
associated hydronephrosis. A magnetic resonance venography showed the inferior
vena cava proximal to the mechanical obstruction was free of thrombosis but was
dilated at 27 mm in the suprarenal location. A hysterectomy was performed and an
8-pound uterus was removed. Intraoperative ultrasound of the inferior vena cava
showed a patent crescent shaped vein with no thrombus and adequate venous blood
flow. Pathology of the uterus showed a large leiomyoma with necrosis. Her lower
extremity symptoms resolved.
PMID- 17038581
TI - Interview with Dr. Heikki Rauvala regarding pivotal advance: analysis of
proinflammatory activity of highly purified eukaryotic recombinant HMGB1
(amphoterin). Interview by Marco E Bianchi.
PMID- 17038582
TI - Impairment of T cell interactions with antigen-presenting cells by
immunosuppressive drugs reveals involvement of calcineurin and NF-kappaB in
immunological synapse formation.
AB - A stable supramolecular cluster in T cells at the contact site of APCs, the
immunological synapse (IS), is essential for full T cell activation. Failure of
IS maturation, as determined by defective relocalization of the TCR/CD3 complex
at the T cell/APC contact site, is linked with T cell hyporesponsiveness. The
effects of clinically used immunosuppressants on these critical events, however,
are undefined. Here, we show that treatment of T cells with cyclosporin A, FK506,
and dexamethasone, which are known to inhibit calcineurin and NF-kappaB,
respectively, but not rapamycin, the inhibitor of mammalian target of rapamycin,
selectively prevented TCR/CD3 relocalization into the IS, while relocalization of
adhesion and cytoskeletal proteins as well as T cell/APC conjugate formation
remained unaltered. The involvement of calcineurin and NF-kappaB in IS maturation
was confirmed by using specific inhibitors of these molecules (FR901725,
gossypol, SN50). FK778, as an inhibitor of DNA replication and also TCR/CD3
activated tyrosine kinases, globally abrogated cytoskeletal, adhesion, and
signaling molecule relocalization, thereby preventing formation of an IS at an
earlier, immature stage along with impaired, antigen-specific T cell/APC
conjugate formation. Collectively, blocking IS formation at distinct stages may
mediate effects on T cell activation of currently used immunosuppressants, apart
from their capacity to block gene transcription, cytokine signaling, and DNA
replication. Furthermore, these data imply novel functions of calcineurin and NF
kappaB for successful IS maturation.
PMID- 17038583
TI - Hereditary hemochromatosis results in decreased iron acquisition and growth by
Mycobacterium tuberculosis within human macrophages.
AB - Iron (Fe) acquisition is essential for the growth of intracellular Mycobacterium
tuberculosis (M.tb). How this occurs is poorly understood. Hereditary
hemochromatosis is an inherited disease in which most cells become overloaded
with Fe. However, hereditary hemochromatosis macrophages have lower than normal
levels of intracellular Fe. This suggests M.tb growth should be slower in those
cells if macrophage intracellular Fe is used by M.tb. Therefore, we compared
trafficking and acquisition of transferrin (Tf)- and lactoferrin (Lf)-chelated Fe
by M.tb within the phagosome of monocyte-derived macrophages (MDM) from healthy
controls and subjects with hereditary hemochromatosis. M.tb in both sets of
macrophages acquired more Fe from Lf than Tf. Fe acquisition by M.tb within
hereditary hemochromatosis macrophages was decreased by 84% from Tf and 92% from
Lf relative to that in healthy control macrophages. There was no difference in Fe
acquired from Tf and Lf by the two macrophage phenotypes. Both acquired 3 times
more Fe from Lf than Tf. M.tb infection and incubation with interferon gamma (IFN
gamma) reduced macrophage Fe acquisition by 20% and 50%, respectively. Both Tf
and Lf colocalized with M.tb phagosomes to a similar extent, independent of
macrophage phenotype. M.tb growth was 50% less in hereditary hemochromatosis
macrophages. M.tb growing within macrophages from subjects with hereditary
hemochromatosis acquire less Fe compared with healthy controls. This is
associated with reduced growth of M.tb. These data support a role for macrophage
intracellular Fe as a source for M.tb growth.
PMID- 17038586
TI - Radar imaging of binary near-Earth asteroid (66391) 1999 KW4.
AB - High-resolution radar images reveal near-Earth asteroid (66391) 1999 KW4 to be a
binary system. The approximately 1.5-kilometer-diameter primary (Alpha) is an
unconsolidated gravitational aggregate with a spin period approximately 2.8
hours, bulk density approximately 2 grams per cubic centimeter, porosity
approximately 50%, and an oblate shape dominated by an equatorial ridge at the
object's potential-energy minimum. The approximately 0.5-kilometer secondary
(Beta) is elongated and probably is denser than Alpha. Its average orbit about
Alpha is circular with a radius approximately 2.5 kilometers and period
approximately 17.4 hours, and its average rotation is synchronous with the long
axis pointed toward Alpha, but librational departures from that orientation are
evident. Exotic physical and dynamical properties may be common among near-Earth
binaries.
PMID- 17038587
TI - The phase-dependent infrared brightness of the extrasolar planet upsilon
Andromedae b.
AB - The star upsilon Andromedae is orbited by three known planets, the innermost of
which has an orbital period of 4.617 days and a mass at least 0.69 that of
Jupiter. This planet is close enough to its host star that the radiation it
absorbs overwhelms its internal heat losses. Here, we present the 24-micrometer
light curve of this system, obtained with the Spitzer Space Telescope. It shows a
variation in phase with the orbital motion of the innermost planet, demonstrating
that such planets possess distinct hot substellar (day) and cold antistellar
(night) faces.
PMID- 17038588
TI - Dynamical configuration of binary near-Earth asteroid (66391) 1999 KW4.
AB - Dynamical simulations of the coupled rotational and orbital dynamics of binary
near-Earth asteroid 66391 (1999 KW4) suggest that it is excited as a result of
perturbations from the Sun during perihelion passages. Excitation of the mutual
orbit will stimulate complex fluctuations in the orbit and rotation of both
components, inducing the attitude of the smaller component to have large
variation within some orbits and to hardly vary within others. The primary's
proximity to its rotational stability limit suggests an origin from spin-up and
disruption of a loosely bound precursor within the past million years.
PMID- 17038589
TI - RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates.
AB - Double-stranded RNA (dsRNA) produced during viral replication is believed to be
the critical trigger for activation of antiviral immunity mediated by the RNA
helicase enzymes retinoic acid-inducible gene I (RIG-I) and melanoma
differentiation-associated gene 5 (MDA5). We showed that influenza A virus
infection does not generate dsRNA and that RIG-I is activated by viral genomic
single-stranded RNA (ssRNA) bearing 5'-phosphates. This is blocked by the
influenza protein nonstructured protein 1 (NS1), which is found in a complex with
RIG-I in infected cells. These results identify RIG-I as a ssRNA sensor and
potential target of viral immune evasion and suggest that its ability to sense 5'
phosphorylated RNA evolved in the innate immune system as a means of
discriminating between self and nonself.
PMID- 17038591
TI - Funding basic agricultural research.
PMID- 17038590
TI - 5'-Triphosphate RNA is the ligand for RIG-I.
AB - The structural basis for the distinction of viral RNA from abundant self RNA in
the cytoplasm of virally infected cells is largely unknown. We demonstrated that
the 5'-triphosphate end of RNA generated by viral polymerases is responsible for
retinoic acid-inducible protein I (RIG-I)-mediated detection of RNA molecules.
Detection of 5'-triphosphate RNA is abrogated by capping of the 5'-triphosphate
end or by nucleoside modification of RNA, both occurring during
posttranscriptional RNA processing in eukaryotes. Genomic RNA prepared from a
negative-strand RNA virus and RNA prepared from virus-infected cells (but not
from noninfected cells) triggered a potent interferon-alpha response in a
phosphatase-sensitive manner. 5'-triphosphate RNA directly binds to RIG-I. Thus,
uncapped 5'-triphosphate RNA (now termed 3pRNA) present in viruses known to be
recognized by RIG-I, but absent in viruses known to be detected by MDA-5 such as
the picornaviruses, serves as the molecular signature for the detection of viral
infection by RIG-I.
PMID- 17038592
TI - Genomics. On your mark. Get set. Sequence!
PMID- 17038593
TI - Nuclear proliferation. North Korea's bomb: boom or bust?
PMID- 17038594
TI - Nobel Prize in economics. Laurels for theories that demystified inflation,
unemployment, and growth.
PMID- 17038595
TI - Nobel Prize in chemistry. Solo winner detailed path From DNA to RNA.
PMID- 17038596
TI - Biomedicine. NIH funds a dozen 'homes' for translational research.
PMID- 17038598
TI - Fusion reactor. ITER's $12 billion gamble.
PMID- 17038597
TI - Stem cells. California stem-cell institute unveils 10-year plan.
PMID- 17038599
TI - Fusion reactor. How to squeeze a plasma.
PMID- 17038600
TI - Brian O'Neill profile. Trying to lasso climate uncertainty.
PMID- 17038601
TI - Neuroscience. Brain evolution on the far side.
PMID- 17038602
TI - Public health. Gerberding defends her transformation of CDC.
PMID- 17038603
TI - Particle physics. Tidy triangle dashes hopes for exotic undiscovered particles.
PMID- 17038604
TI - Cooperating over water issues in the Middle East.
PMID- 17038605
TI - What happens to the whistleblowers?
PMID- 17038606
TI - A problem with mentoring.
PMID- 17038607
TI - Mice, pain, and empathy.
PMID- 17038608
TI - Ecology. Millennium ecosystem assessment: research needs.
PMID- 17038609
TI - Genetics. The bacterial world gets smaller.
PMID- 17038610
TI - Applied physics. Seeking the ultimate nanolaser.
PMID- 17038611
TI - Cell biology. Balancing life-or-death decisions.
PMID- 17038612
TI - Geochemistry. How fast does gold trickle out of volcanoes?
PMID- 17038613
TI - Chemistry. Strong-arming molecular dynamics.
PMID- 17038614
TI - Chemistry. Quantum chemistry of complex systems.
PMID- 17038616
TI - Self-assembly of CdTe nanocrystals into free-floating sheets.
AB - In their physical dimensions, surface chemistry, and degree of anisotropic
interactions in solution, CdTe nanoparticles are similar to proteins. We
experimentally observed their spontaneous, template-free organization into free
floating particulate sheets, which resemble the assembly of surface layer (S
layer) proteins. Computer simulation and concurrent experiments demonstrated that
the dipole moment, small positive charge, and directional hydrophobic attraction
are the driving forces for the self-organization process. The data presented here
highlight the analogy of the solution behavior of the two vastly different
classes of chemical structures.
PMID- 17038615
TI - The 160-kilobase genome of the bacterial endosymbiont Carsonella.
AB - Previous studies have suggested that the minimal cellular genome could be as
small as 400 kilobases. Here, we report the complete genome sequence of the
psyllid symbiont Carsonella ruddii, which consists of a circular chromosome of
159,662 base pairs, averaging 16.5% GC content. It is by far the smallest and
most AT-rich bacterial genome yet characterized. The genome has a high coding
density (97%) with many overlapping genes and reduced gene length. Genes for
translation and amino acid biosynthesis are relatively well represented, but
numerous genes considered essential for life are missing, suggesting that
Carsonella may have achieved organelle-like status.
PMID- 17038617
TI - Dynamic stark control of photochemical processes.
AB - A method is presented for controlling the outcome of photochemical reactions by
using the dynamic Stark effect due to a strong, nonresonant infrared field. The
application of a precisely timed infrared laser pulse reversibly modifies
potential energy barriers during a chemical reaction without inducing any real
electronic transitions. Dynamic Stark control (DSC) is experimentally
demonstrated for a nonadiabatic photochemical reaction, showing substantial
modification of reaction channel probabilities in the dissociation of IBr. The
DSC process is nonperturbative and insensitive to laser frequency and affects all
polarizable molecules, suggesting broad applicability.
PMID- 17038618
TI - Rapid early development of circumarctic peatlands and atmospheric CH4 and CO2
variations.
AB - An analysis of 1516 radiocarbon dates demonstrates that the development of the
current circumarctic peatlands began approximately 16.5 thousand years ago (ka)
and expanded explosively between 12 and 8 ka in concert with high summer
insolation and increasing temperatures. Their rapid development contributed to
the sustained peak in CH4 and modest decline of CO2 during the early Holocene and
likely contributed to CH4 and CO2 fluctuations during earlier interglacial and
interstadial transitions. Given the decreased tempo of peatland initiation in the
late Holocene and the transition of many from fens (which generated high levels
of CH4) to ombrotrophic bogs, a neoglacial expansion of northern peatlands cannot
explain the increase in atmospheric CH4 that occurred after 6 ka.
PMID- 17038619
TI - Gold in magmatic hydrothermal solutions and the rapid formation of a giant ore
deposit.
AB - The Ladolam hydrothermal system, on Lihir Island, Papua New Guinea, hosts one of
the youngest and largest gold deposits in the world. Several deep (more than 1
kilometer) geothermal wells were drilled beneath the ore bodies to extract water
at >275 degrees C and to facilitate open-pit mining. Using a titanium down-hole
sampler, we determined that the deep geothermal brine of magmatic origin contains
approximately 15 parts per billion gold. At the current gold flux of 24 kilograms
per year, this deposit could have formed within approximately 55,000 years. The
combination of sustained metal flux and efficient metal precipitation led to the
formation of a giant hydrothermal gold deposit in a short period.
PMID- 17038620
TI - Cellular and subcellular structure of neoproterozoic animal embryos.
AB - Stereoblastic embryos from the Doushantuo Formation of China exhibit occasional
asynchronous cell division, with diminishing blastomere volume as cleavage
proceeded. Asynchronous cell division is common in modern embryos, implying that
sophisticated mechanisms for differential cell division timing and embryonic cell
lineage differentiation evolved before 551 million years ago. Subcellular
structures akin to organelles, coated yolk granules, or lipid vesicles occur in
these embryos. Paired reniform structures within embryo cells may represent
fossil evidence of cells about to undergo division. Embryos exhibit no evidence
of epithelial organization, even in embryos composed of approximately 1000 cells.
Many of these features are compatible with metazoans, but the absence of
epithelialization is consistent only with a stem-metazoan affinity for Doushantuo
embryos.
PMID- 17038621
TI - CDK2-dependent phosphorylation of FOXO1 as an apoptotic response to DNA damage.
AB - The function of cyclin-dependent kinase 2 (CDK2) is often abolished after DNA
damage. The inhibition of CDK2 plays a central role in DNA damage-induced cell
cycle arrest and DNA repair. However, whether CDK2 also influences the survival
of cells under genotoxic stress is unknown. Forkhead box O (FOXO) transcription
factors are emerging as key regulators of cell survival. CDK2 specifically
phosphorylated FOXO1 at serine-249 (Ser249) in vitro and in vivo. Phosphorylation
of Ser249 resulted in cytoplasmic localization and inhibition of FOXO1. This
phosphorylation was abrogated upon DNA damage through the cell cycle checkpoint
pathway that is dependent on the protein kinases Chk1 and Chk2. Moreover,
silencing of FOXO1 by small interfering RNA diminished DNA damage-induced death
in both p53-deficient and p53-proficient cells. This effect was reversed by
restored expression of FOXO1 in a manner depending on phosphorylation of Ser249.
Functional interaction between CDK2 and FOXO1 provides a mechanism that regulates
apoptotic cell death after DNA strand breakage.
PMID- 17038622
TI - Tissue geometry determines sites of mammary branching morphogenesis in
organotypic cultures.
AB - The treelike structures of many organs, including the mammary gland, are
generated by branching morphogenesis, a reiterative process of branch initiation
and invasion from a preexisting epithelium. Using a micropatterning approach to
control the initial three-dimensional structure of mouse mammary epithelial
tubules in culture, combined with an algorithm to quantify the extent of
branching, we found that the geometry of tubules dictates the position of
branches. We predicted numerically and confirm experimentally that branches
initiate at sites with a local minimum in the concentration of autocrine
inhibitory morphogens, such as transforming growth factor-beta. These results
reveal that tissue geometry can control organ morphogenesis by defining the local
cellular microenvironment, a finding that has relevance to control of invasion
and metastasis.
PMID- 17038623
TI - Tandem riboswitch architectures exhibit complex gene control functions.
AB - Riboswitches are structured RNAs typically located in the 5' untranslated regions
of bacterial mRNAs that bind metabolites and control gene expression. Most
riboswitches sense one metabolite and function as simple genetic switches.
However, we found that the 5' region of the Bacillus clausii metE messenger RNA
includes two riboswitches that respond to S-adenosylmethionine and coenzyme B12.
This tandem arrangement yields a composite gene control system that functions as
a two-input Boolean NOR logic gate. These findings and the discovery of
additional tandem riboswitch architectures reveal how simple RNA elements can be
assembled to make sophisticated genetic decisions without involving protein
factors.
PMID- 17038624
TI - A mutant chaperone converts a wild-type protein into a tumor-specific antigen.
AB - Monoclonal antibodies have become important therapeutic agents against certain
cancers. Many tumor-specific antigens are mutant proteins that are predominantly
intracellular and thus not readily accessible to monoclonal antibodies. We found
that a wild-type transmembrane protein could be transformed into a tumor-specific
antigen. A somatic mutation in the chaperone gene Cosmc abolished function of a
glycosyltransferase, disrupting O-glycan Core 1 synthesis and creating a tumor
specific glycopeptidic neo-epitope consisting of a monosaccharide and a specific
wild-type protein sequence. This epitope induced a high-affinity, highly
specific, syngeneic monoclonal antibody with antitumor activity. Such tumor
specific glycopeptidic neo-epitopes represent potential targets for monoclonal
antibody therapy.
PMID- 17038625
TI - A small microbial genome: the end of a long symbiotic relationship?
AB - Intracellular bacteria are characterized by genome reduction. The 422,434-base
pair genome of Buchnera aphidicola BCc, primary endosymbiont of the aphid Cinara
cedri, is approximately 200 kilobases smaller than the previously sequenced B.
aphidicola genomes. B. aphidicola BCc has lost most metabolic functions,
including the ability to synthesize the essential amino acid tryptophan and
riboflavin. In addition, most retained genes are evolving rapidly. Possibly, B.
aphidicola BCc is losing its symbiotic capacity and is being complemented (and
might be replaced) by the highly abundant coexisting secondary symbiont.
PMID- 17038626
TI - TLRs in the Gut. III. Immune responses to flagellin in Crohn's disease: good,
bad, or irrelevant?
AB - Recent observations suggest that bacterial flagellin may be a target of the
seemingly aberrant innate and adaptive immune responses that are associated with
Crohn's disease. This article discusses the evidence that supports a role for
flagellin in Crohn's disease and considers the potential roles of these responses
in the pathophysiology of this disorder.
PMID- 17038627
TI - Inchinkoto, a herbal medicine, and its ingredients dually exert Mrp2/MRP2
mediated choleresis and Nrf2-mediated antioxidative action in rat livers.
AB - Inchinkoto (ICKT), a herbal medicine, has been recognized in Japan and China as a
"magic bullet" for jaundice. To explore potent therapeutic agents for
cholestasis, the effects of ICKT or its ingredients on multidrug resistance
associated protein 2 (Mrp2/ MRP2)-mediated choleretic activity, as well as on
antioxidative action, were investigated using rats and chimeric mice with livers
that were almost completely repopulated with human hepatocytes. Biliary excretion
of Mrp2 substrates and the protein mass, subcellular localization, and mRNA level
of Mrp2 were assessed in rats after 1-wk oral administration of ICKT or genipin,
a major ingredient of ICKT. Administration of ICKT or genipin to rats for 7 days
increased bile flow and biliary excretion of bilirubin conjugates. Mrp2 protein
and mRNA levels and Mrp2 membrane densities in the bile canaliculi and renal
proximal tubules were significantly increased in ICKT- or genipin-treated rat
livers and kidneys. ICKT and genipin, thereby, accelerated the disposal of
intravenously infused bilirubin. The treatment also increased hepatic levels of
heme oxygenase-1 and GSH by a nuclear factor-E2-related factor (Nrf2)-dependent
mechanism. Similar effects of ICKT on MRP2 expression levels were observed in
humanized livers of chimeric mice. In conclusion, these findings provide the
rationale for therapeutic options of ICKT and its ingredients that should
potentiate bilirubin disposal in vivo by enhancing Mrp2/MRP2-mediated secretory
capacities in both livers and kidneys as well as Nrf2-mediated antioxidative
actions in the treatment of cholestatic liver diseases associated with jaundice.
PMID- 17038628
TI - Beneficial effect of glatiramer acetate (Copaxone) on immune modulation of
experimental hepatic fibrosis.
AB - While CD8 subsets activate hepatic fibrosis, natural killer (NK) cells exhibit
antifibrotic activity. Glatiramer acetate (GA) is an immune modulator for
multiple sclerosis. We assessed the potential impact of GA on mouse hepatic
fibrogenesis. Hepatic fibrosis was induced in C57BL/6 mice by intraperitoneal
administration of carbon tetrachloride (CCl(4)) for 6 wk. During the last 2 wk,
animals were also treated with either GA (200 mu/day ip) or medium and compared
with naive and fibrotic mice (8 animals/group). GA markedly attenuated fibrosis
without altering reactive oxygen species production. By morphometric measurement
of Sirius red-stained tissue sections, the relative fibrosis area decreased from
5.28 +/- 0.32% (mean +/- SE) in the untreated CCl(4) group to 2.01 +/- 0.28% in
CCl(4)+GA-treated animals, compared with 0.38 +/- 0.07% in naive mice. alpha
Smooth muscle actin immunoblotting and mRNA expression revealed a similar
pattern. Serum aminotransferase and Ishak-Knodell necroinflammatory score were
markedly elevated, to the same extent, in both CCl(4)-treated groups. Fibrosis
induction was associated with significant increase in CD8 subsets and decrease in
CD4 T cells. After GA treatment, however, NK content, CD4(+)CD25(+)FoxP3(+)
cells, hepatic expression of tumor necrosis factor-related apoptosis-inducing
ligand (TRAIL), and apoptosis of hepatic stellate cells were all increased. Serum
interleukin (IL)-10 levels markedly rose, whereas IL-4 fell. In vitro activation
of human hepatic stellate cells cocultured with hepatitis C virus-derived
peripheral blood lymphocytes decreased when lymphocytes were preincubated with GA
before coculture. In an animal model of hepatic fibrosis, GA has an antifibrotic
effect associated with decreased CD8 cells and reduced serum IL-4 levels and
increased NK cells, CD4(+)CD25(+)FoxP3(+) cells, TRAIL, and elevated serum IL-10
levels.
PMID- 17038629
TI - Azoxymethane protects intestinal stem cells and reduces crypt epithelial mitosis
through a COX-1-dependent mechanism.
AB - Azoxymethane (AOM) is a potent DNA-damaging agent and carcinogen that induces
intestinal and colonic tumors in rodents. Evaluation of the stem cell population
by colony formation assay reveals that, within 8 h after treatment, AOM (10
mg/kg) elicited a prosurvival response. In wild-type (WT) mice, AOM treatment
induced a 2.5-fold increase in intestinal crypt stem cell survival. AOM treatment
increased stem cell survival in cyclooxygenase (COX)-2(-/-) but not COX-1(-/-)
mice, confirming a role of COX-1 in the AOM-induced increase in stem cell
survival. COX-1 mRNA and protein expression as well as COX-1-derived PGE(2)
synthesis were increased 8 h after AOM treatment. Immunohistochemical staining of
COX-1 demonstrated expression of the enzyme in the crypt epithelial cells,
especially in the columnar epithelial cells between the Paneth cells adjacent to
the stem cell zone. WT mice receiving AOM exhibited increased intestinal
apoptosis and a simultaneous reduction in crypt mitotic figures within 8 h of
injection. There were no significant differences in baseline or AOM-induced
intestinal epithelial apoptosis between WT and COX-1(-/-) mice, but there was a
complete reversal of the AOM-mediated reduction in mitosis in COX-1(-/-) mice.
This suggests that COX-1-derived PGE(2) may play a key role in the early phase of
intestinal tumorigenesis in response to DNA damage and suggests that COX-1 may be
a potential therapeutic target in this model of colon cancer.
PMID- 17038630
TI - MEK-ERK inhibition corrects the defect in VLDL assembly in HepG2 cells: potential
role of ERK in VLDL-ApoB100 particle assembly.
AB - OBJECTIVE: Hepatic VLDL assembly is defective in HepG2 cells, resulting in the
secretion of immature triglyceride-poor LDL-sized apoB particles. We investigated
the mechanisms underlying defective VLDL assembly in HepG2 and have obtained
evidence implicating the MEK-ERK pathway. METHODS AND RESULTS: HepG2 cells
exhibited considerably higher levels of the ERK1/2 mass and activity compared
with primary hepatocytes. Inhibition of ERK1/2 using the MEK1/MEK2 inhibitor,
U0126 (but not the inactive analogue) led to a significant increase in apoB
secretion. In the presence of oleic acid, ERK1/2 inhibition caused a major shift
in the lipoprotein distribution with a majority of particles secreted as VLDL, an
effect independent of insulin. In contrast, overexpression of constitutively
active MEK1 decreased apoB and large VLDL secretion. MEK1/2 inhibition
significantly increased both cellular and microsomal TG mass, and mRNA levels for
DGAT-1 and DGAT-2. In contrast to ERK, modulation of the PI3-K pathway or
inhibition of the p38 MAP kinase, had no effect on lipoprotein density profile.
Modulation of the MEK-ERK pathway in primary hamster hepatocytes led to changes
in apoB secretion and altered the density profile of apoB-containing
lipoproteins. CONCLUSIONS: Inhibition of the overactive ras-MEK-ERK pathway in
HepG2 cells can correct the defect in VLDL assembly leading to the secretion of
large, VLDL-sized particles, similar to primary hepatocytes, implicating the MEK
ERK cascade in VLDL assembly in the HepG2 model. Modulation of this pathway in
primary hepatocytes also regulates apoB secretion and appears to alter the
formation of VLDL-1 sized particles.
PMID- 17038631
TI - Macrophage phospholipid transfer protein deficiency and ApoE secretion: impact on
mouse plasma cholesterol levels and atherosclerosis.
AB - OBJECTIVE: PLTP and apoE play important roles in lipoprotein metabolism and
atherosclerosis. It is known that formation of macrophage-derived foam cells
(which highly express PLTP and apoE) is the critical step in the process of
atherosclerosis. We investigated the relationship between PLTP and apoE in
macrophages and the atherogenic relevance in a mouse model. METHODS AND RESULTS:
We transplanted PLTP-deficient mouse bone marrow into apoE-deficient mice (PLTP-/
--> apoE-/-), creating a mouse model with PLTP deficiency and apoE expression
exclusively in the macrophages. We found that PLTP-/- --> apoE-/- mice have
significantly lower PLTP activity, compared with controls (WT --> apoE-/-; 20%,
P<0.01). On a Western diet, PLTP-/- --> apoE-/- mice have significantly lower
plasma apoE than that of WT --> apoE-/- mice (63%, P<0.001), and PLTP-deficient
macrophages secrete significantly less apoE than WT macrophages (44%, P<0.01).
Moreover, PLTP-/- --> apoE-/- mice have significantly higher plasma cholesterol
(98%, P<0.001) and phospholipid (107%, P<0.001) than that of WT --> apoE-/- mice,
thus increasing atherosclerotic lesions in the aortic arch and root (403%,
P<0.001), as well as the entire aorta (298%, P<0.001). CONCLUSIONS: Macrophage
PLTP deficiency causes a significant reduction of apoE secretion from the cells,
and this in turn promotes the accumulation of cholesterol in the circulation and
accelerates the development of atherosclerosis.
PMID- 17038632
TI - Expression of LPL in endothelial-intact artery results in lipid deposition and
vascular cell adhesion molecule-1 upregulation in both LPL and ApoE-deficient
mice.
AB - OBJECTIVE: Overexpression of lipoprotein lipase (LPL) in deendothelialized artery
led to profound localized lipid deposition. In this study the role of LPL in
atherogenesis in endothelial-intact carotid arteries was assessed in genetically
hyperlipidemic LPL- and ApoE-deficient mice. METHODS AND RESULTS: Human wild-type
LPL (hLPLwt), catalytically inactive LPL (hLPL194), or control alkaline
phosphatase (hAP) were expressed in endothelial-intact carotid arteries via
adenoviral vectors. Compared with Ad-hAP, lipid deposition in the arterial wall
increased 10.0- and 5.1-fold for Ad-hLPLwt and Ad-hLPL194 in LPL-deficient mice,
and 10.6- and 6.2-fold in ApoE-deficient mice, respectively. Vascular cell
adhesion molecule-1 (VCAM-1) was upregulated in Ad-hLPLwt and Ad-hLPL194
transferred arteries. CONCLUSIONS: Endothelial cell associated LPL, either active
or inactive, in the arterial wall is a strong proatherosclerotic factor in both
LPL- and ApoE-deficient mice.
PMID- 17038633
TI - Macrophage low-density lipoprotein receptor-related protein deficiency enhances
atherosclerosis in ApoE/LDLR double knockout mice.
AB - OBJECTIVE: In vitro studies implicate that the low-density lipoprotein receptor
(LDLR)-related protein (LRP) in macrophages has a pro-atherogenic potential. In
the present study, we investigated the in vivo role of macrophage specific LRP in
atherogenesis independent of its role in the uptake of lipoproteins. METHODS AND
RESULTS: We generated macrophage-specific LRP-deficient mice on an apoE/LDLR
double-deficient background. Macrophage LRP deletion did not affect plasma
cholesterol and triglyceride levels, lipoprotein distribution, and blood monocyte
counts. Nevertheless, macrophage LRP deficiency resulted in a 1.8-fold increase
in total atherosclerotic lesion area in the aortic root of 18-week-old mice.
Moreover, LRP deficiency also resulted in a relatively higher number of advanced
lesions. Whereas macrophage and smooth muscle cell content did not differ between
LRP-deficient mice and control littermates, a 1.7-fold increase in collagen
content and 2.3-fold decrease in relative number of CD3+ T cells were observed in
lesions from macrophage specific LRP-deficient mice. CONCLUSIONS: Our data
demonstrate that independent of its role in lipoprotein uptake, absence of LRP in
macrophages resulted in more advanced atherosclerosis and in lesions that
contained more collagen and less CD3+ T cells. In contrast to previous in vitro
studies, we conclude that macrophage LRP has an atheroprotective potential and
may modulate the extracellular matrix in the atherosclerotic lesions.
PMID- 17038634
TI - Circulating leukocyte-derived microparticles predict subclinical atherosclerosis
burden in asymptomatic subjects.
AB - OBJECTIVE: To clarify circulating microparticles (MP) relationships with
preclinical atherosclerosis. METHODS AND RESULTS: In 216 subjects without
cardiovascular disease, we assessed: (1) annexin V-positive, platelet-derived,
endothelium-derived and leukocyte-derived circulating MP by capture on annexin V,
anti-GPIb, anti-CD105, and anti-CD11a antibody-coated wells, respectively; (2)
Framingham risk, metabolic syndrome, and low-grade inflammation by risk factors
measurement including hsCRP; and (3) subclinical atherosclerosis by ultrasound
examination of carotid, abdominal aorta, and femoral arteries. Number of sites
with plaque ranged from 0 to 3 and plaque burden was classified into 0 to 1 or 2
to 3 sites disease. Leukocyte-derived MP level was higher in the presence than in
the absence of moderate to high Framingham risk (P<0.05), metabolic syndrome
(P<0.01), high C-reactive protein (CRP) (P<0.05), or 2- to 3-sites disease
(P<0.01), and correlated positively with number of metabolic syndrome components
(P<0.001), tertiles of fibrinogen (P<0.001), and number of diseased sites
(P<0.01). In multivariate analysis, 2- to 3-sites disease was independently
associated with leukocyte-derived MP level (P<0.05), Framingham risk (P<0.001),
and metabolic syndrome (P<0.01). None of the other MP types correlated with risk
markers or atherosclerosis. CONCLUSIONS: Leukocyte-derived MP, identified by
affinity for CD11a, are increased in subjects with ultrasound evidence of
subclinical atherosclerosis, unveiling new directions for atherosclerosis
research.
PMID- 17038635
TI - Plasma adiponectin levels in relation to carotid intima media thickness and
markers of insulin resistance.
AB - BACKGROUND: Circulating adiponectin is a marker for insulin sensitivity, derived
from fat cells. It is largely unknown if adiponectin is also an independent
marker for early atherosclerosis. METHODS AND RESULTS: Plasma adiponectin levels
were measured in 373 men and 514 women of middle-age by a time-resolved
immunofluorometric assay. The subjects were sampled stratified for degree of
insulin sensitivity (HOMA-IR). An ultrasound measurement of the right common
carotid artery intima media thickness (IMT) was made. When the distribution of
adiponectin was stratified into sex-specific quartiles (Q1 to Q4), men in Q4
differed from Q1 in higher mean age and high-density lipoprotein (HDL)
cholesterol, but lower blood pressure, HbA1c, HOMA-index, and body mass index.
Women showed similar associations. Mean IMT for men was significantly lower
(P=0.03) in adiponectin Q4 as compared with Q1 when adjusted for age, waist,
smoking, HDL cholesterol, and diastolic blood pressure. When adding HbA1c and
HOMA to the model, the association was no longer significant (P=0.15). In women
no difference in IMT was noticed across adiponectin quartiles. CONCLUSIONS:
Plasma adiponectin is a marker of glucose metabolism and obesity and shows an
inverse age-adjusted association with carotid ultrasound IMT in men, but not in
women. This association is attenuated after adjustments for other risk factors.
PMID- 17038636
TI - Suppression of RAGE as a basis of simvastatin-dependent plaque stabilization in
type 2 diabetes.
AB - OBJECTIVE: Receptor for advanced glycation end products (AGEs) (RAGE) plays a
central role in the process of plaque rupture in diabetic patients. Recently, it
has been reported that RAGE may be downregulated by improving glycemic control.
In contrast, despite being well known that RAGE may be induced in human vessels
in a glucose-independent fashion, also by myeloperoxidase (MPO)-dependent AGE
generation, no data exist regarding the possibility of a pharmacological
modulation of glucose-independent RAGE generation. Thus, the aim of this study
was to characterize the effect of simvastatin on the expression of RAGE and RAGE
dependent plaque-destabilizing genes in human atherosclerotic plaques. METHODS
AND RESULTS: Seventy type 2 diabetic patients with asymptomatic carotid artery
stenosis (>70%) were randomized to American Heart Association (AHA) step 1 diet
plus simvastatin (40 mg/d) or AHA step 1 diet alone for 4 months before
endarterectomy. Plaque expression of MPO, AGEs, RAGE, NF-kappaB, COX-2, mPGES-1,
matrix metalloproteinase (MMP)-2 and MMP-9, lipid and oxidized LDL (oxLDL)
content, procollagen 1, and interstitial collagen was analyzed by
immunohistochemistry and Western blot; zymography was used to detect MMP
activity. Plaques from the simvastatin group had less (P<0.0001) immunoreactivity
for MPO, AGEs, RAGE, p65, COX-2, mPGES-1, MMP-2, and MMP-9, lipids and oxLDL;
reduced (P<0.0001) gelatinolytic activity; increased (P<0.0001) procollagen 1 and
collagen content; and fewer (P<0.0001) macrophages, T-lymphocytes, and HLA-DR+
cells. Of interest, RAGE inhibition by simvastatin, observed not only in plaque
sections but also in plaque-derived macrophages, was reverted by addition of AGEs
in vitro. CONCLUSIONS: This study supports the hypothesis that simvastatin
inhibits plaque RAGE expression by decreasing MPO-dependent AGE generation. This
effect in turn might contribute to plaque stabilization by inhibiting the
biosynthesis of PGE2-dependent MMPs, responsible for plaque rupture.
PMID- 17038637
TI - Apolipoprotein CIII-induced THP-1 cell adhesion to endothelial cells involves
pertussis toxin-sensitive G protein- and protein kinase C alpha-mediated nuclear
factor-kappaB activation.
AB - OBJECTIVE: Plasma apolipoprotein CIII (apoCIII) independently predicts risk for
coronary heart disease (CHD). We recently reported that apoCIII directly enhances
adhesion of human monocytes to endothelial cells (ECs), and identified the
activation of PKC alpha as a necessary upstream event of enhanced monocyte
adhesion. This study tested the hypothesis that apoCIII activates PKC alpha in
human monocytic THP-1 cells, leading to NF-kappaB activation. METHODS AND
RESULTS: Among inhibitors specific to PKC activators, phosphatidylcholine
specific phospholipase C (PC-PLC) inhibitor D609 limited apoCIII-induced PKC
alpha activation and THP-1 cell adhesion. ApoCIII increased PC-PLC activity in
THP-1 cells, resulting in PKC alpha activation. Pertussis toxin (PTX) inhibited
apoCIII-induced PC-PLC activation and subsequent PKC alpha activation,
implicating PTX-sensitive G protein pathway. ApoCIII further activated nuclear
factor-kappaB (NF-kappaB) through PKC alpha in THP-1 cells and augmented beta1
integrin expression. The NF-kappaB inhibitor peptide SN50 partially inhibited
apoCIII-induced beta1-integrin expression and THP-1 cell adhesion. ApoCIII-rich
VLDL had similar effects to apoCIII alone. CONCLUSIONS: PTX-sensitive G protein
pathway participates critically in PKC alpha stimulation in THP-1 cells exposed
to apoCIII, activating NF-kappaB, and increasing beta1-integrin. This action
causes monocytic cells to adhere to endothelial cells. Furthermore, because
leukocyte NF-kappaB activation contributes to inflammatory aspects of
atherogenesis, apoCIII may stimulate diverse inflammatory responses through
monocyte activation.
PMID- 17038638
TI - Physical activity improves long-term stroke outcome via endothelial nitric oxide
synthase-dependent augmentation of neovascularization and cerebral blood flow.
AB - Physical activity upregulates endothelial nitric oxide synthase (eNOS), improves
endothelium function, and protects from vascular disease. Here, we tested whether
voluntary running would enhance neovascularization and long-term recovery
following mild brain ischemia. Wild-type mice were exposed to 30 minutes of
middle-cerebral artery occlusion (MCAo) and reperfusion. Continuous voluntary
running on wheels conferred long-term upregulation of eNOS in the vasculature and
of endothelial progenitor cells (EPCs) in the spleen and bone marrow (BM). This
was associated with higher numbers of circulating EPCs in the blood and enhanced
neovascularization. Moreover, engraftment of TIE2/LacZ-positive BM-derived cells
was increased in the ischemic brain. Four weeks after the insult, trained animals
showed higher numbers of newly generated cells in vascular sites, increased
density of perfused microvessels and sustained augmentation of cerebral blood
flow within the ischemic striatum. Moreover, running conferred tissue sparing and
improved functional outcome at 4 weeks. The protective effects of running on
angiogenesis and outcome were completely abolished when animals were treated with
a NOS inhibitor or the antiangiogenic compound endostatin after brain ischemia,
and in animals lacking eNOS expression. Voluntary physical activity improves long
term stroke outcome by eNOS-dependent mechanisms related to improved angiogenesis
and cerebral blood flow.
PMID- 17038639
TI - ATP release from activated neutrophils occurs via connexin 43 and modulates
adenosine-dependent endothelial cell function.
AB - Extracellular ATP liberated during hypoxia and inflammation can either signal
directly on purinergic receptors or can activate adenosine receptors following
phosphohydrolysis to adenosine. Given the association of polymorphonuclear
leukocytes (PMNs) with adenine-nucleotide/nucleoside signaling in the
inflammatory milieu, we hypothesized that PMNs are a source of extracellular ATP.
Initial studies using high-performance liquid chromatography and luminometric ATP
detection assays revealed that PMNs release ATP through activation-dependent
pathways. In vitro models of endothelial barrier function and
neutrophil/endothelial adhesion indicated that PMN-derived ATP signals through
endothelial adenosine receptors, thereby promoting endothelial barrier function
and attenuating PMN/endothelial adhesion. Metabolism of extracellular ATP to
adenosine required PMNs, and studies addressing these metabolic steps revealed
that PMN express surface ecto-apyrase (CD39). In fact, studies with PMNs derived
from cd39(-/-) mice showed significantly increased levels of extracellular ATP
and lack of ATP dissipation from their supernatants. After excluding lytic ATP
release, we used pharmacological strategies to reveal a potential mechanism
involved in PMN-dependent ATP release (eg, verapamil, dipyridamole, brefeldin A,
18-alpha-glycyrrhetinic acid, connexin-mimetic peptides). These studies showed
that PMN ATP release occurs through connexin 43 (Cx43) hemichannels in a
protein/phosphatase-A-dependent manner. Findings in human PMNs were confirmed in
PMNs derived from induced Cx43(-/-) mice, whereby activated PMNs release less
than 15% of ATP relative to littermate controls, whereas Cx43 heterozygote PMNs
were intermediate in their capacity for ATP release (P<0.01). Taken together, our
results identify a previously unappreciated role for Cx43 in activated PMN ATP
release, therein contributing to the innate metabolic control of the inflammatory
milieu.
PMID- 17038640
TI - Cyclic AMP imaging in adult cardiac myocytes reveals far-reaching beta1
adrenergic but locally confined beta2-adrenergic receptor-mediated signaling.
AB - Beta(1)- and beta(2)-adrenergic receptors (betaARs) are known to differentially
regulate cardiomyocyte contraction and growth. We tested the hypothesis that
these differences are attributable to spatial compartmentation of the second
messenger cAMP. Using a fluorescent resonance energy transfer (FRET)-based
approach, we directly monitored the spatial and temporal distribution of cAMP in
adult cardiomyocytes. We developed a new cAMP-FRET sensor (termed HCN2-camps)
based on a single cAMP binding domain of the hyperpolarization activated cyclic
nucleotide-gated potassium channel 2 (HCN2). Its cytosolic distribution, high
dynamic range, and sensitivity make HCN2-camps particularly well suited to
monitor subcellular localization of cardiomyocyte cAMP. We generated HCN2-camps
transgenic mice and performed single-cell FRET imaging on freshly isolated
cardiomyocytes. Whole-cell superfusion with isoproterenol showed a moderate
elevation of cAMP. Application of various phosphodiesterase (PDE) inhibitors
revealed stringent control of cAMP through PDE4>PDE2>PDE3. The beta(1)AR-mediated
cAMP signals were entirely dependent on PDE4 activity, whereas beta(2)AR-mediated
cAMP was under control of multiple PDE isoforms. beta(1)AR subtype-specific
stimulation yielded approximately 2-fold greater cAMP responses compared with
selective beta(2)-subtype stimulation, even on treatment with the nonselective
PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) (DeltaFRET, 17.3+/-1.3%
[beta(1)AR] versus 8.8+/-0.4% [beta(2)AR]). Treatment with pertussis toxin to
inactivate G(i) did not affect cAMP production. Localized beta(1)AR stimulation
generated a cAMP gradient propagating throughout the cell, whereas local
beta(2)AR stimulation did not elicit marked cAMP diffusion. Our data reveal that
in adult cardiac myocytes, beta(1)ARs induce far-reaching cAMP signals, whereas
beta(2)AR-induced cAMP remains locally confined.
PMID- 17038641
TI - Time course of degradation of cardiac troponin I in patients with acute ST
elevation myocardial infarction: the ASSENT-2 troponin substudy.
AB - Although measurement of troponin is widely used for diagnosing acute myocardial
infarction (AMI), its diagnostic potential may be increased by a more complete
characterization of its molecular appearance and degradation in the blood. The
aim of this study was to define the time course of cardiac troponin I (cTnI)
degradation in patients with acute ST-elevation myocardial infarction (STEMI). In
the ASSENT-2 substudy, 26 males hospitalized with STEMI were randomized to 2
different thrombolytic drugs within 6 hours after onset of symptoms. Blood
samples were obtained just before initiation of thrombolysis and at 30 minutes
intervals (7 samples per patient). Western blot analysis was performed using anti
cTnI antibodies and compared with serum concentrations of cTnI. All patients
exceeded the cTnI cutoff for AMI during the sampling period; at initiation of
therapy, 23 had elevated cTnI values. All patients demonstrated 2 bands on
immunoblot: intact cTnI and a single degradation product as early as 90 minutes
after onset of symptoms. On subsequent samples, 15 of 26 patients showed multiple
degradation products with up to 7 degradation bands. The appearance of fragments
was correlated with higher levels of cTnI (P<0.001) and time to initiation of
treatment (P=0.058). This study defines for the first time the initial time
course of cTnI degradation in STEMI. Intact cTnI and a single degradation product
were detectable on immunoblot as early as 90 minutes after onset of symptoms with
further degradation after 165 minutes. Infarct size and time to initiation of
treatment was the major determinant for degradation.
PMID- 17038642
TI - Adenosine restores angiotensin II-induced contractions by receptor-independent
enhancement of calcium sensitivity in renal arterioles.
AB - Adenosine is coupled to energy metabolism and regulates tissue blood flow by
modulating vascular resistance. In this study, we investigated isolated, perfused
afferent arterioles of mice, which were subjected to desensitization during
repeated applications of angiotensin II. Exogenously applied adenosine restores
angiotensin II-induced contractions by increasing calcium sensitivity of the
arterioles, along with augmented phosphorylation of the regulatory unit of the
myosin light chain. Adenosine restores angiotensin II-induced contractions via
intracellular action, because inhibition of adenosine receptors do not prevent
restoration, but inhibition of NBTI sensitive adenosine transporters does.
Restoration was prevented by inhibition of Rho-kinase, protein kinase C, and the
p38 mitogen-activated protein kinase, which modulate myosin light chain
phosphorylation and thus calcium sensitivity in the smooth muscle. Furthermore,
adenosine application increased the intracellular ATP concentration in LuciHEK
cells. The results of the study suggest that restoration of the angiotensin II
induced contraction by adenosine is attributable to the increase of the calcium
sensitivity by phosphorylation of the myosin light chain. This can be an
important component of vascular control during ischemic and hypoxic conditions.
Additionally, this mechanism may contribute to the mediation of the
tubuloglomerular feedback by adenosine in the juxtaglomerular apparatus of the
kidney.
PMID- 17038643
TI - Coxsackievirus B3 induces T regulatory cells, which inhibit cardiomyopathy in
tumor necrosis factor-alpha transgenic mice.
AB - Innate immunity promotes both the generation of autoimmunity and immunoregulation
of adaptive immunity. Transgenic mice expressing the tumor necrosis factor-alpha
(TNF-alpha) gene under the cardiac myosin promoter (TNF1.6 mice) develop dilated
cardiomyopathy. Transgenic mice show extensive cardiac inflammation, suggesting
that immunopathogenic mechanisms may promote cardiomyopathy. Two coxsackievirus
B3 (CVB3) variants infect and replicate in the heart. H3 variant is highly
myocarditic, but H310A1 variant activates CD4(+) T regulatory cells, which
protect against viral myocarditis. T-cell depletion of TNF1.6 mice using
monoclonal anti-CD3 or anti-CD4 antibody significantly reduced heart size and
plasma troponin I concentrations compared with control TNF1.6 mice.
Cardiomyopathy in TNF1.6 mice correlates to a CD4(+)Th1 response and autoimmune
IgG2a antibodies. TNF1.6 mice infected with H310A1 virus reduced heart size and
cardiac inflammation corresponding to the activation of CD4(+)CD25(+)FoxP3(+) (T
regulatory cells). Immunosuppression is dependent on IL-10 but not TGFbeta.
Adoptive transfer of the CD4(+)CD25(+) cells from H310A1-infected mice into
uninfected TNF1.6 recipients abrogated cardiomyopathy. Exogenous administration
of recombinant TNF-alpha to H310A1-infected mice for 4 days abrogated
immunosuppression. Cardiac enlargement in TNF1.6 mice is partly attributable to T
cell activation and humoral autoimmunity caused by cytokine expression. T
regulatory cells induced by H310A1 virus abrogate autoimmunity caused by TNF
alpha overexpression. H3 virus infection induces high levels of systemic TNF
alpha, whereas H310A1 virus does not. The low TNF-alpha response during H310A1
infections is likely responsible for the T regulatory cell response in these
animals.
PMID- 17038645
TI - Plaque angiogenesis versus compensatory arteriogenesis in atherosclerosis.
PMID- 17038644
TI - Calmodulin kinase II inhibition shortens action potential duration by
upregulation of K+ currents.
AB - The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is
activated by elevated intracellular Ca(2+) (Ca(2+)(i)), and mice with chronic
myocardial CaMKII inhibition (Inh) resulting from transgenic expression of a
CaMKII inhibitory peptide (AC3-I) unexpectedly showed action potential duration
(APD) shortening. Inh mice exhibit increased L-type Ca(2+) current (I(Ca)),
because of upregulation of protein kinase A (PKA) activity, and decreased CaMKII
dependent phosphorylation of phospholamban (PLN). We hypothesized that CaMKII is
a molecular signal linking Ca(2+)(i) to repolarization. Whole cell voltage-clamp
recordings revealed that the fast transient outward current (I(to,f)) and the
inward rectifier current (I(K1)) were selectively upregulated in Inh, compared
with wild-type (WT) and transgenic control, mice. Breeding Inh mice with mice
lacking PLN returned I(to,f) and I(K1) to control levels and equalized the APD
and QT intervals in Inh mice to control and WT levels. Dialysis of AC3-I into WT
cells did not result in increased I(to,f) or I(K1), suggesting that enhanced
cardiac repolarization in Inh mice is an adaptive response to chronic CaMKII
inhibition rather than an acute effect of reduced CaMKII activity. Increasing PKA
activity, by cell dialysis with cAMP, or inhibition of PKA did not affect I(K1)
in WT cells. Dialysis of WT cells with cAMP also reduced I(to,f), suggesting that
PKA upregulation does not increase repolarizing K(+) currents in Inh mice. These
findings provide novel in vivo and cellular evidence that CaMKII links Ca(2+)(i)
to cardiac repolarization and suggest that PLN may be a critical CaMKII target
for feedback regulation of APD in ventricular myocytes.
PMID- 17038646
TI - A single second messenger: several possible cellular responses depending on
distinct subcellular pools.
PMID- 17038647
TI - A new paradigm: calcium independent and caveolae internalization dependent
release of nitric oxide by the endothelial nitric oxide synthase.
PMID- 17038648
TI - New insights in the role of cardiac myosin binding protein C as a regulator of
cardiac contractility.
PMID- 17038649
TI - Signaling mechanisms in ischemic preconditioning: interaction of PKCepsilon and
MitoK(ATP) in the inner membrane of mitochondria.
PMID- 17038650
TI - Allograft vasculopathy versus atherosclerosis.
AB - Over the last 4 decades, heart transplantation (HTx) has evolved as a mainstream
therapy for heart failure. Approximately half of patients needing HTx have organ
failure consequent to atherosclerosis. Despite advances in immunosuppressive
drugs, long-term success of HTx is limited by the development of a particular
type of coronary atherosclerosis, referred to as cardiac allograft vasculopathy
(CAV). Although the exact pathogenesis of CAV remains to be established, there is
strong evidence that CAV involves immunologic mechanisms operating in a milieu of
nonimmunologic risk factors. The immunologic events constitute the principal
initiating stimuli, resulting in endothelial injury and dysfunction, altered
endothelial permeability, with consequent myointimal hyperplasia and
extracellular matrix synthesis. Lipid accumulation in allograft arteries is
prominent, with lipoprotein entrapment in the subendothelial tissue, through
interactions with proteoglycans. The apparent endothelial "intactness" in human
coronary arteries of the transplanted heart suggest that permeability and
function of the endothelial barrier altered. Various insults to the vascular bed
result in vascular smooth muscle cell (SMC) activation. Activated SMCs migrate
from the media into the intima, proliferate, and elaborate cytokines and
extracellular matrix proteins, resulting in luminal narrowing and impaired
vascular function. Arteriosclerosis is a broad term that is used to encompass all
diseases that lead to arterial hardening, including native atherosclerosis,
postangioplasty restenosis, vein bypass graft occlusion, and CAV. These diseases
exhibit many similarities; however, they are distinct from one another in
numerous ways as well. The present review summarizes the current understanding of
the risk factors and the pathophysiological similarities and differences between
CAV and atherosclerosis.
PMID- 17038651
TI - Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic
nucleotide phosphodiesterases.
AB - A current challenge in cellular signaling is to decipher the complex
intracellular spatiotemporal organization that any given cell type has developed
to discriminate among different external stimuli acting via a common signaling
pathway. This obviously applies to cAMP and cGMP signaling in the heart, where
these cyclic nucleotides determine the regulation of cardiac function by many
hormones and neuromediators. Recent studies have identified cyclic nucleotide
phosphodiesterases as key actors in limiting the spread of cAMP and cGMP, and in
shaping and organizing intracellular signaling microdomains. With this new role,
phosphodiesterases have been promoted from the rank of a housekeeping attendant
to that of an executive officer.
PMID- 17038652
TI - Antihypertensive treatment in reducing the risk of dementia.
PMID- 17038653
TI - Migraine relief after patent foramen ovale closure: should vascular risk factor
control be achieved first?
PMID- 17038654
TI - Previous cardiac abnormalities in subarachnoid hemorrhage may also have
background genetic polymorphisms.
PMID- 17038655
TI - Asymmetric dimethylarginine and cerebrovascular disorders in humans.
PMID- 17038659
TI - Tuberculosis among foreign-born persons in the United States: achieving
tuberculosis elimination.
AB - RATIONALE: In the United States, the number of annual reported cases of
tuberculosis (TB) among U.S.-born persons declined by 62% from 1993 to 2004, but
increased by 5% among foreign-born persons. Over half of all reported cases of TB
in the United States occur among foreign-born persons, most of these due to
activation of latent TB infection (LTBI). Current guidelines recommend targeting
only foreign-born persons who entered the United States within the previous 5 yr
for LTBI testing. OBJECTIVE: We sought to assess the epidemiologic basis for this
guideline. METHODS: We calculated TB case rates among foreign-born persons,
stratified by duration of United States residence and world region of origin. We
determined the number of cases using 2004 U.S. TB surveillance data, and
calculated case rates using population data from the 2004 American Community
Survey. MEASUREMENTS AND MAIN RESULTS: In 2004, a total of 14,517 cases of TB
were reported; 3,444 (24%) of these were among foreign-born persons who had
entered the United States more than 5 yr previously. The rate of TB disease among
foreign-born persons was 21.5/100,000, compared with 2.7/100,000 for U.S.-born
persons, and varied by duration of residence and world region of origin.
CONCLUSIONS: Almost one-quarter of all TB cases in the United States occur among
foreign-born persons who have resided in the United States for longer than 5 yr;
case rates for such persons from selected regions of origin remain substantially
elevated. To eliminate TB, we must address the burden of LTBI in this high-risk
group.
PMID- 17038660
TI - Tidal hyperinflation during low tidal volume ventilation in acute respiratory
distress syndrome.
AB - RATIONALE: Tidal volume and plateau pressure limitation decreases mortality in
acute respiratory distress syndrome. Computed tomography demonstrated a small,
normally aerated compartment on the top of poorly aerated and nonaerated
compartments that may be hyperinflated by tidal inflation. OBJECTIVES: We
hypothesized that despite tidal volume and plateau pressure limitation, patients
with a larger nonaerated compartment are exposed to tidal hyperinflation of the
normally aerated compartment. MEASUREMENTS AND MAIN RESULTS: Pulmonary computed
tomography at end-expiration and end-inspiration was obtained in 30 patients
ventilated with a low tidal volume (6 ml/kg predicted body weight). Cluster
analysis identified 20 patients in whom tidal inflation occurred largely in the
normally aerated compartment (69.9 +/- 6.9%; "more protected"), and 10 patients
in whom tidal inflation occurred largely within the hyperinflated compartments
(63.0 +/- 12.7%; "less protected"). The nonaerated compartment was smaller and
the normally aerated compartment was larger in the more protected patients than
in the less protected patients (p = 0.01). Pulmonary cytokines were lower in the
more protected patients than in the less protected patients (p < 0.05).
Ventilator-free days were 7 +/- 8 and 1 +/- 2 d in the more protected and less
protected patients, respectively (p = 0.01). Plateau pressure ranged between 25
and 26 cm H(2)O in the more protected patients and between 28 and 30 cm H(2)O in
the less protected patients (p = 0.006). CONCLUSIONS: Limiting tidal volume to 6
ml/kg predicted body weight and plateau pressure to 30 cm H(2)O may not be
sufficient in patients characterized by a larger nonaerated compartment.
PMID- 17038661
TI - Elevated morbidity and health care use in children with obstructive sleep apnea
syndrome.
AB - RATIONALE: Health care use, a reliable measure of morbidity, is noticeably higher
1 yr before obstructive sleep apnea syndrome (OSAS) diagnosis in preschool
children. It is not clear at what age OSAS-related morbidity becomes expressed.
OBJECTIVE: To explore morbidity and health care use among children with OSAS
starting from first year of life. METHODS: Case-control study, starting from the
first year of life to date of OSAS diagnosis, among 156 patients (age range, 3-5
yr) and their pair-matched healthy control subjects, by age, sex, primary care
physician, and geographic location. MEASUREMENTS: Patients with OSAS underwent
nocturnal polysomnography studies. Medical records during hospital visits were
reviewed for diagnosis. Variables of health care use were obtained from
computerized databases of Clalit Health Care Services, the largest health
maintenance organization in Israel. MAIN RESULTS: From the first year of life to
date of OSAS diagnosis, children with OSAS had 40% more (p = 0.048) hospital
visits, 20% more repeated (two or more) visits (p < 0.0001), and higher
consumption of antiinfective and respiratory system drugs (p < 0.0001). Referrals
of children with OSAS to otolaryngology surgeons and pediatric pulmonologists
were higher from Year 1 (p < 0.0001) to date of OSAS diagnosis, especially in
Year 4 (odds ratio, 9.4; 95% confidence interval, 4.2-21.1). The 215% elevation
(p < 0.0001) in health care use of the OSAS group was due mainly to higher
occurrence of respiratory tract morbidity (p < 0.0001). CONCLUSIONS:
Practitioners should be aware that starting in Year 1 until date of diagnosis,
children with OSAS have higher health care use, mostly related to respiratory
diseases.
PMID- 17038662
TI - Unique uptake of acid-prepared mesoporous spheres by lung epithelial and
mesothelioma cells.
AB - Lung cancers, malignant mesotheliomas (MM), and fibrosis are devastating diseases
with limited treatment strategies, in part due to poorly-effective drug delivery
to affected areas of lung. We hypothesized that acid-prepared mesoporous spheres
(APMS) (1-2 microm diameter, 40 A pore size) might be effective vehicles for
pulmonary chemotherapeutic drug delivery. To assess this, APMS, chemically
modified with different surface molecules (lipid, a linker having a terminal
amine group, a thiol group, or tetraethylene glycol [TEG]), were evaluated for
uptake and possible cytotoxic effects after in vitro administration to murine
alveolar epithelial Type II (C10) and human mesothelioma (MM) cells and after
intrapleural or intranasal administration to C57Bl/6 mice. APMS coated with TEG
(APMS-TEG) were most efficiently taken up by C10 and MM cells. The mechanism of
cell uptake was rapid, actin-dependent, and did not involve clathrin- or caveolae
mediated mechanisms nor fusion of membrane-bound APMS with lysosomes. When
injected intrapleurally in mice, APMS-TEG were taken up by both CD45-positive and
-negative cells of the diaphragm, lung, and spleen, whereas APMS administered by
the intranasal route were predominantly in lung epithelial cells and alveolar
macrophages. After intrapleural or intranasal administration, APMS were
nonimmunogenic and nontoxic as evaluated by differential cell counts and lactate
dehydrogenase levels in bronchoalveolar and pleural lavage fluids. In the
treatment of lung and pleural diseases, APMS-TEG may be useful tools to deliver
chemotherapeutic drugs or molecular constructs.
PMID- 17038663
TI - IL-2 and IL-18 attenuation of airway hyperresponsiveness requires STAT4, IFN
gamma, and natural killer cells.
AB - IL-18 is known to induce IFN-gamma production, which is enhanced when combined
with IL-2. In the present study, we investigated whether the combination of
exogenous IL-2 and IL-18 alters airway hyperresponsiveness (AHR) and airway
inflammation. Sensitized mice exposed to ovalbumin (OVA) challenge developed AHR,
inflammatory cells in the bronchoalveolar lavage (BAL) fluid, and increases in
levels of Th2 cytokines and goblet cell numbers. The combination of IL-2 and IL
18, but neither alone, prevented these changes while increasing levels of IL-12
and IFN-gamma. The combination of IL-2 and IL-18 was ineffective in IFN-gamma
deficient and signal transducer and activator of transcription (STAT)4-deficient
mice. Flow cytometry analysis showed significant increases in numbers of IFN
gamma-positive natural killer (NK) cells in the lung after treatment with the
combination therapy, and transfer of lung NK cells isolated from sensitized and
challenged mice treated with the combination significantly suppressed AHR and BAL
eosinophilia. These data demonstrate that the combination of IL-2 and IL-18
prevents AHR and airway inflammation, likely through IL-12-mediated induction of
IFN-gamma production in NK cells.
PMID- 17038665
TI - Fibroblast growth factor 2 modulates transforming growth factor beta signaling in
mouse embryonic fibroblasts and human ESCs (hESCs) to support hESC self-renewal.
AB - Fibroblast growth factor 2 (FGF2) is known to promote self-renewal of human
embryonic stem cells (hESCs). In addition, it has been shown that transforming
growth factor beta (TGFbeta) signaling is crucial in that the
TGFbeta/Activin/Nodal branch of the pathway needs to be activated and the bone
morphogenic protein (BMP)/GDF branch repressed to prevent differentiation. This
holds particularly true for Serum Replacement-based medium containing BMP-like
activity. We have reinvestigated a widely used protocol for conditioning hESC
medium with mouse embryonic fibroblasts (MEFs). We show that FGF2 acts on MEFs to
release supportive factors and reduce differentiation-inducing activity. FGF2
stimulation experiments with supportive and nonsupportive MEFs followed by genome
wide expression profiling revealed that FGF2 regulates the expression of key
members of the TGFbeta pathway, with Inhba, Tgfb1, Grem1, and Bmp4 being the most
likely candidates orchestrating the above activities. In addition, restimulation
experiments in hESCs combined with global expression analysis revealed downstream
targets of FGF2 signaling in these cells. Among these were the same factors
previously identified in MEFs, thus suggesting that FGF2, at least in part,
promotes self-renewal of hESCs by modulating the expression of TGFbeta ligands,
which, in turn, act on hESCs in a concerted and autocrine manner.
PMID- 17038664
TI - Role of protein cavities on unfolding volume change and on internal dynamics
under pressure.
AB - The effects of two single point cavity forming mutations, F110S and I7S, on the
unfolding volume change (DeltaV(0)) of azurin from Pseudomonas aeruginosa and on
the internal dynamics of the protein fold under pressure were probed by the
fluorescence and phosphorescence emission of Trp-48, deeply buried in the compact
hydrophobic core of the macromolecule. Pressure-induced unfolding, monitored by
the shift of the center of mass of the fluorescence spectrum, showed that
DeltaV(0) is in the range of 60-70 mL/mol, not significantly different between
cavity mutants and compact azurin species such as the wild-type and the mutant
C3A/C26A, in which the superficial disulphide has been removed. The lack of extra
volume in F110S and I7S proves that the engineered cavities, 40 A(3) in I7S and
100 A(3) in F110S, are filled with water molecules. Changes in flexibility of the
protein matrix around the chromophore were monitored by the intrinsic
phosphorescence lifetime (tau(0)). The application of pressure in the
predenaturation range initially decreases the internal flexibility of azurin, the
trend eventually reverting on approaching unfolding. The main difference between
compact folds, wild-type and C3A/C26A, and cavity mutants is that the inversion
point is powered from approximately 3 kbar to 1.5 kbar for F110S and <0.1 kbar
for I7S, meaning that in the latter species pressure-induced internal hydration
dominates very early over any compaction of the globular fold resulting from the
reduction of internal free volume. The similar response between wild-type and the
significantly less-stable C3A/C26A mutant suggests that thermodynamic stability
per se is not the dominant factor regulating pressure-induced internal hydration
of proteins.
PMID- 17038666
TI - Impaired downregulation following erythropoietin receptor activation in non-small
cell lung carcinoma.
AB - Recent evidence confirms the presence of erythropoietin receptors on a variety of
cancer cells. This has raised concerns about the use of erythropoiesis
stimulating agents in the treatment of cancer-related anemia. Having previously
identified expression of functional erythropoietin receptors in a non-small cell
lung carcinoma cell line, H838, which activated key signaling pathways in
response to erythropoietin stimulation, we now demonstrate impaired
downregulation of the erythropoietin receptor in these tumor cells. The
erythropoietin receptor is not ubiquitinated following erythropoietin stimulation
in this cancer cell line, and there is no turnover of the receptor in either
unstimulated or stimulated cells. Compounding this blunted response is impaired
SOCS3 induction downstream of erythropoietin stimulation and an extremely delayed
SOCS1 response. If this finding in non-small cell lung carcinoma is a widespread
phenomenon, then impaired erythropoietin receptor downregulation and degradation
in tumor cells has clinical implications for those patients receiving
erythropoiesis-stimulating agents for cancer-related anemia.
PMID- 17038667
TI - Identification of candidate murine esophageal stem cells using a combination of
cell kinetic studies and cell surface markers.
AB - The identification and characterization of esophageal stem cells are critical to
our understanding of the biology of the esophageal epithelium in health and
disease. However, the proliferative compartment within the mouse esophageal
epithelium remains poorly characterized. Here, we report that the basal cells of
the mouse esophagus can be separated into three phenotypically and functionally
distinct subpopulations based on the expression of alpha(6) integrin and
transferrin receptor (CD71). Cells that express high levels of alpha(6) integrin
and low levels of CD71, termed alpha(6)(bri)CD71(dim), are a minor subpopulation
of small and undifferentiated cells that are enriched for label-retaining cells
and thus represent a putative esophageal stem cell population. Conversely, cells
expressing high levels of both alpha(6) integrin and CD71
(alpha(6)(bri)CD71(bri)), the majority of basal esophageal cells, are enriched
for actively cycling cells and therefore represent a transit-amplifying
population. Kinetic analyses revealed that a third cell population, which is
alpha(6) integrin-dim and CD71-bright (alpha(6)(dim)), is destined to leave the
basal layer and differentiate.
PMID- 17038668
TI - Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic
neurons from human embryonic stem cells using the bone morphogenic protein
antagonist noggin.
AB - It is currently not known whether dopamine (DA) neurons derived from human
embryonic stem cells (hESCs) can survive in vivo and alleviate symptoms in models
of Parkinson disease (PD). Here, we report the use of Noggin (a bone morphogenic
protein antagonist) to induce neuroectodermal cell development and increase the
yield of DA neurons from hESCs. A combination of stromal-derived inducing
activity and Noggin markedly enhanced the generation of neuroepithelial
progenitors that could give rise to DA neurons. In addition, Noggin diminished
the occurrence of a fibroblast-like Nestin-positive precursor population that
differentiated into myocytes. After transplantation of differentiated hESCs to a
rodent model of PD, some grafts contained human midbrain-like DA neurons. This
protocol demonstrates hESC derivation and survival of human DA neurons
appropriate for cell therapy in PD.
PMID- 17038669
TI - Multipotent cell fate of neural crest-like cells derived from embryonic stem
cells.
AB - Neural crest cells migrate throughout the embryo and differentiate into diverse
derivatives: the peripheral neurons, cranial mesenchymal cells, and melanocytes.
Because the neural crest cells have critical roles in organogenesis, detailed
elucidation of neural crest cell differentiation is important in developmental
biology. We recently reported that melanocytes could be induced from mouse ESCs.
Here, we improved the culture system and showed the existence of neural crest
like precursors. The addition of retinoic acid to the culture medium reduced the
hematopoiesis and promoted the expression of the neural crest marker genes. The
colonies formed contained neural crest cell derivatives: neurons and glial cells,
together with melanocytes. This suggested that neural crest-like cells assuming
multiple cell fates had been generated in these present cultures. To isolate the
neural crest-like cells, we analyzed the expression of c-Kit, a cell-surface
protein expressed in the early stage of neural crest cells in vivo. The c-Kit
positive (c-Kit(+)) cells appeared as early as day 9 of the culture period and
expressed the transcriptional factors Sox10 and Snail, which are expressed in
neural crest cells. When the c-Kit(+) cells were separated from the cultures and
recultured, they frequently formed colonies containing neurons, glial cells, and
melanocytes. Even a single c-Kit(+) cell formed colonies that contained these
three cell types, confirming their multipotential cell fate. The c-Kit(+) cells
were also capable of migrating along neural crest migratory pathways in vivo.
These results indicate that the c-Kit(+) cells isolated from melanocyte
differentiating cultures of ESCs are closely related to neural crest cells.
PMID- 17038670
TI - Distinct population of hair cell progenitors can be isolated from the postnatal
mouse cochlea using side population analysis.
AB - In mammals, the permanence of hearing loss is due mostly to the incapacity of the
cochlea to replace lost mechano-receptor cells (i.e., hair cells [HCs]). The
generation of new HCs from a renewable source of progenitors is a principal
requirement for developing a cell therapy within this sensory organ. A subset of
stem cells, termed side population (SP), has been identified in several tissues
of mammals. The ATP-binding cassette transporter Abcg2/Bcrp1 contributes to the
specification of the SP phenotype and is proposed as a universal marker for
stem/progenitor cells. A defining character of these SP cells is a high efflux
capacity for Hoechst dye. Here, we demonstrate that Abcg2 transporter is
expressed with two other stem/progenitor cell markers (i.e., Nestin and Musashi1)
in distinct and overlapping domains of the supporting cells within the postnatal
cochlea. We have developed and describe a fluorescence-activated cell sorting
(FACS) technique that enables the purification of a discrete subpopulation of SP
supporting cells from the early postnatal mouse cochlea based on their ability to
exclude Hoechst dye. These FACS-isolated cells can divide and express markers of
stem/progenitor cells such as Abcg2, a determinant of the SP phenotype, and
Musashi1, a neural stem/progenitor cell marker. These markers can differentiate
cells expressing markers of HCs and supporting cells in vitro. Our observation
that these SP cells are capable of differentiating into HC-like cells implies a
possible use for such cells (i.e., the replacement of lost auditory HCs within
damaged cochlea).
PMID- 17038672
TI - Generation and characterization of rabbit embryonic stem cells.
AB - We described the derivation of four stable pluripotent rabbit embryonic stem cell
(ESC) lines, one (RF) from blastocysts fertilized in vivo and cultured in vitro
and three (RP01, RP02, and RP03) from parthenogenetic blastocysts. These ESC
lines have been cultivated for extended periods (RF >1 year, RP01 >8 months, RP02
>8 months, and RP03 >6 months) in vitro while maintaining expression of
pluripotent ESC markers and a normal XY or XX karyotype. The ESCs from all lines
expressed alkaline phosphatase, transcription factor Oct-4, stage-specific
embryonic antigens (SSEA-1, SSEA-3, and SSEA-4), and the tumor-related antigens
(TRA-1-60 and TRA-1-81). Similar to human and mouse ESCs, rabbit ESCs expressed
pluripotency (Oct-4, Nanog, SOX2, and UTF-1) and signaling pathway genes
(fibroblast growth factor, WNT, and transforming growth factor pathway).
Morphologically, rabbit ESCs resembled primate ESCs, whereas their proliferation
characteristics were more like those seen in mouse ESCs. Rabbit ESCs were induced
to differentiate into many cell types in vitro and formed teratomas with
derivatives of the three major germ layers in vivo when injected into severe
combined immunodeficient mice. Our results showed that pluripotent, stable ESC
lines could be derived from fertilized and parthenote-derived rabbit embryos.
PMID- 17038671
TI - Microarray analyses support a role for Nurr1 in resistance to oxidative stress
and neuronal differentiation in neural stem cells.
AB - Nurr1 is an orphan nuclear receptor required for the development of midbrain
dopaminergic neurons. To better understand the molecular consequences of Nurr1
expression, we compared the transcriptomes of two independent control and Nurr1
expressing NSC lines using Affymetrix cDNA microarrays. These data reveal the
regulation of genes involved in promoting cell survival (trophic/growth factors
and stress response genes) and in preventing cell death (decreased caspase-3 and
caspase-11 expression). We found that conditioned medium from Nurr1-expressing
NSC lines enhanced the survival of midbrain dopaminergic neurons in primary
cultures and that Nurr1-expressing NSC lines themselves were more resistant to
oxidative stress. These findings are accompanied by a dynamic pattern of gene
regulation that is consistent with a role for Nurr1 in promoting both the
acquisition of brain-region-specific identity (Engrailed-1) and neuronal
differentiation (tubulin beta III). Interestingly, our gene expression profiles
suggested that tenascin-C was regulated by Nurr1 in developing dopaminergic
neurons. This was further confirmed in vitro and in Nurr1 knockout mice where low
levels of tenascin-C mRNA were observed. Analysis of tenascin-C-null mice
revealed an increase in the number of Nurr1(+) cells that become tyrosine
hydroxylase-positive (TH(+)) dopaminergic neurons at embryonic day 11.5,
suggesting that tenascin-C normally delays the acquisition of TH by Nurr1(+)
precursors. Thus, our results confirm the presence of both secreted and cell
intrinsic survival signals modulated by Nurr1 and suggest that Nurr1 is a key
regulator of both survival and dopaminergic differentiation.
PMID- 17038673
TI - Molecular analysis of LEFTY-expressing cells in early human embryoid bodies.
AB - Human ESCs (HESCs) are self-renewing pluripotent cell lines that are derived from
the inner cell mass of blastocyst-stage embryos. These cells can produce
terminally differentiated cells representing the three embryonic germ layers. We
thus hypothesized that during the course of in vitro differentiation of HESCs,
progenitor-like cells are transiently formed. We demonstrated that LEFTY
proteins, which are known to play a major role during mouse gastrulation, are
transiently expressed during HESC differentiation. Moreover, LEFTY proteins
seemed to be exclusively expressed by a certain population of cells in the early
human embryoid bodies that does not overlap with the population expressing the
ESC marker OCT4. We also showed that LEFTY expression is regulated at the
cellular transcription level by molecular labeling of LEFTY-positive cells. A DNA
microarray analysis of LEFTY-overexpressing cells revealed a signature of cell
surface markers such as CADHERIN 2 and 11. Expression of LEFTY controlled by
NODAL appears to have a substantial role in mesodermal origin cell population
establishment, since inhibition of NODAL activity downregulated expression not
only of LEFTY A and LEFTY B but also of BRACHYURY, an early mesodermal marker. In
addition, other mesodermal lineage-related genes were downregulated, and this was
accompanied by an upregulation in ectoderm-related genes. We propose that during
the initial step of HESC differentiation, mesoderm progenitor-like cells appear
via activation of the NODAL pathway. Our analysis suggests that in vitro
differentiation of HESCs can model early events in human development.
PMID- 17038674
TI - Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like
organization of human embryonic stem cell-derived endothelium in vitro.
AB - The molecular mechanisms that regulate human blood vessel formation during early
development are largely unknown. Here we used human ESCs (hESCs) as an in vitro
model to explore early human vasculogenesis. We demonstrated that stromal cell
derived factor-1 (SDF-1) and CXCR4 were expressed concurrently with hESC-derived
embryonic endothelial differentiation. Human ESC-derived embryonic endothelial
cells underwent dose-dependent chemotaxis to SDF-1, which enhanced vascular
network formation in Matrigel. Blocking of CXCR4 signaling abolished capillary
like structures induced by SDF-1. Inhibition of the SDF-1/CXCR4 signaling pathway
by AMD3100, a CXCR4 antagonist, disrupted the endothelial sprouting outgrowth
from human embryoid bodies, suggesting that the SDF-1/CXCR4 axis plays a critical
role in regulating initial vessel formation, and may function as a morphogen
during human embryonic vascular development.
PMID- 17038675
TI - Sarcoma derived from cultured mesenchymal stem cells.
AB - To study the biodistribution of MSCs, we labeled adult murine C57BL/6 MSCs with
firefly luciferase and DsRed2 fluorescent protein using nonviral Sleeping Beauty
transposons and coinfused labeled MSCs with bone marrow into irradiated
allogeneic recipients. Using in vivo whole-body imaging, luciferase signals were
shown to be increased between weeks 3 and 12. Unexpectedly, some mice with the
highest luciferase signals died and all surviving mice developed foci of sarcoma
in their lungs. Two mice also developed sarcomas in their extremities. Common
cytogenetic abnormalities were identified in tumor cells isolated from different
animals. Original MSC cultures not labeled with transposons, as well as
independently isolated cultured MSCs, were found to be cytogenetically abnormal.
Moreover, primary MSCs derived from the bone marrow of both BALB/c and C57BL/6
mice showed cytogenetic aberrations after several passages in vitro, showing that
transformation was not a strain-specific nor rare event. Clonal evolution was
observed in vivo, suggesting that the critical transformation event(s) occurred
before infusion. Mapping of the transposition insertion sites did not identify an
obvious transposon-related genetic abnormality, and p53 was not overexpressed.
Infusion of MSC-derived sarcoma cells resulted in malignant lesions in secondary
recipients. This new sarcoma cell line, S1, is unique in having a cytogenetic
profile similar to human sarcoma and contains bioluminescent and fluorescent
genes, making it useful for investigations of cellular biodistribution and tumor
response to therapy in vivo. More importantly, our study indicates that sarcoma
can evolve from MSC cultures.
PMID- 17038676
TI - Evidence for transmission of Plasmodium vivax among a duffy antigen negative
population in Western Kenya.
AB - We present evidence that a parasite with characteristics of Plasmodium vivax is
being transmitted among Duffy blood group-negative inhabitants of Kenya. Thirty
two of 4,901 Anopheles gambiae and An. funestus (0.65%) collected in Nyanza
Province were ELISA positive for the P. vivax circumsporozoite protein VK 247.
All positives were found late in the rainy season, when An. funestus
predominated, and disproportionately many were found at a single village. A P.
vivax specific sequence of the SSU rRNA gene was amplified from three of six
ELISA-positive mosquitoes. Erythrocytes from 31 children, including 9
microscopically diagnosed as infected with P. vivax, were negative by flow
cytometry for the Fy3 or Fy6 epitopes, which indicate Duffy blood group
expression. A DNA fragment specific for the C terminus of the gene for P. vivax
merozoite surface protein 1 (MSP-1) was amplified from the blood of four of these
children and subsequently sequenced from two.
PMID- 17038677
TI - Antibodies to Plasmodium vivax apical membrane antigen 1: persistence and
correlation with malaria transmission intensity.
AB - The antibody responses to the apical membrane antigen 1 of the Plasmodium vivax
(PvAMA-1) were investigated in subjects living in areas of Brazil with different
levels of malaria transmission. The prevalence and the levels of IgG to PvAMA-1
increased with the time of exposure. The frequency of a positive response and the
mean IgG level were higher in areas where malaria prevalence was more intense,
especially among non-infected subjects exposed to moderate transmission over a
period of 20 years. The proportions and levels of IgG1and IgG3 isotypes were
significantly higher among those subjects with long-term exposure. Antibodies,
mainly IgG1, to PvAMA-1 persisted for seven years among subjects briefly exposed
to malaria in an outbreak outside the Brazilian malaria-endemic area. These data
show the highly immunogenic properties of PvAMA-1 and emphasize its possible use
as a malaria vaccine candidate.
PMID- 17038679
TI - Placental malaria in women with South-East Asian ovalocytosis.
AB - Malaria during pregnancy, which is characterized by the accumulation of infected
erythrocytes in the placenta, often has severe consequences for the mother and
newborn. We assessed the effect of the genetic trait South-East Asian
ovalocytosis (SAO) on placental malaria in women from Papua New Guinea. In
children, this trait confers protection against cerebral malaria, but not against
mild malaria disease, malaria parasitemia, or severe malaria anemia. Using a case
control approach, we found that SAO women suffer from placental malaria, and SAO
infected erythrocytes can sequester in the placenta, but heavy placental
infections tended to be less common in SAO than in control pregnant women.
Reduced prevalence and severity of placental infection associated with SAO were
observed only for primigravid women, who are the group at highest risk of
suffering from severe manifestations of placental malaria. Furthermore, we found
that the prevalence of the SAO trait was lower among pregnant women than among
non-pregnant controls.
PMID- 17038678
TI - Changing patterns of Plasmodium blood-stage infections in the Wosera region of
Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis.
AB - In Papua New Guinea (PNG), complex patterns of malaria commonly include single
and mixed infections of Plasmodium falciparum, P. vivax, P. malariae, and P.
ovale. Here, we assess recent epidemiologic characteristics of Plasmodium blood
stage infections in the Wosera region through four cross-sectional surveys
(August 2001 to June 2003). Whereas previous studies performed here have relied
on blood smear/light microscopy (LM) for diagnosing Plasmodium species
infections, we introduce a newly developed, post-polymerase chain reaction (PCR),
semi-quantitative, ligase detection reaction-fluorescent microsphere assay (LDR
FMA). A direct comparison of the two methods for > 1,100 samples showed that
diagnosis was concordant for > 80% of the analyses performed for P. falciparum
(PF), P. vivax (PV), and P. malariae (PM). Greater sensitivity of the LDR-FMA
accounted for 75% of the discordance between diagnoses. Based on LM, the
prevalence of blood-stage PF, PV, and PM infections was found to be markedly
reduced compared with an early 1990s survey. In addition, there were significant
shifts in age distribution of infections, with PV becoming the most common
parasite in children < 4 years of age. Consistent with previous studies,
prevalence of all Plasmodium species infections increased significantly in
samples analyzed by the PCR-based LDR-FMA. This increase was most pronounced for
PM, PO, and mixed infections and in adolescent (10-19 years) and adult age
groups, suggesting that LM may lead to under-reported prevalence of less common
Plasmodium species, infection complexity, and a skewed distribution of infections
towards younger age groups. This study shows that the application of LDR-FMA
diagnosis in large epidemiologic studies or malaria control interventions is
feasible and may contribute novel insights regarding the epidemiology of malaria.
PMID- 17038680
TI - Efficacy of three chloroquine-primaquine regimens for treatment of Plasmodium
vivax malaria in Colombia.
AB - Plasmodium vivax malaria is an important cause of morbidity in Central and South
America. In Colombia, this is the most prevalent malaria infection, representing
75% of the reported cases. To define the efficacy of the chloroquine and
primaquine regimen to eliminate hypnozoites and prevent relapses, we conducted a
random controlled clinical trial of three primaquine regimens in an open-label
study. We evaluated the anti-relapse efficacy of total primaquine doses of 45,
105, and 210 mg administered at a dosage of 15 mg/day in 210 adults with P. vivax
infection from the northwestern region of Colombia. Cure rates for blood-stage P.
vivax malaria by day 28 of follow-up were 100% in all groups. Post-treatment
reappearance of parasitemia during the six months of follow-up was 45%, 36.6% and
17.6%, respectively, for each group. When compared with other groups,
administration of 210 mg was a significant protection factor for reappearance of
parasitemia in a malaria-endemic area.
PMID- 17038681
TI - Experimental infection of the neotropical malaria vector Anopheles darlingi by
human patient-derived Plasmodium vivax in the Peruvian Amazon.
AB - Malaria transmission from humans to mosquitoes is modulated by human host immune
factors. Understanding mechanisms by which the human host response may impair
parasite infectivity for mosquitoes has direct implications for the development
of transmission-blocking vaccines. We hypothesized that despite a low
transmission intensity of malaria in the Peruvian Amazon region of Iquitos,
transmission-blocking immunity against Plasmodium vivax might be common, given an
unexpectedly high proportion of asymptomatic parasitemic individuals in this
region. To test this hypothesis, the ability of symptomatic P. vivax malaria
patients to experimentally infect wild-caught outbred Anopheles darlingi
mosquitoes was tested using the indirect membrane feeding technique. Only half
(52/102) of P. vivax parasitemic patients successfully infected mosquitoes.
Transmitters were more likely to have gametocytes (OR 6.35, P = 0.003), high
parasitemia (OR 3.79, P = 0.024), and, in terms of basic clinical parameters, a
slower pulse rate (mean +/- SD: 82.3 +/- 12.3 versus 88.7 +/- 13.5, P = 0.016)
than non-transmitters. Log(10) gametocytemia and log(10) real-time reverse
transcriptase Pvs25 PCR quantifying gametocytes were significantly and positively
correlated with oocyst counts (correlation coefficient 0.505, R2 = 0.26, P =
0.001). These experiments are the first to establish a system of determining
transmission patterns in experimental infection of outbred natural neotropical
malaria vectors in the Amazon region. Patients with P. vivax inefficiently infect
outbred An. darlingi mosquitoes, raising the possibility that some degree of
naturally occurring transmission-blocking immunity is present on a population
basis in the Peruvian Amazon, an area of low intensity of malaria transmission.
PMID- 17038682
TI - Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical
regions and susceptibility to antifolate drugs.
AB - The increasing use of sulfadoxine-pyrimethamine (SP) for the treatment of
chloroquine-resistant Plasmodium falciparum has resulted in increased reports of
SP resistance of P. falciparum worldwide. Selection of SP-resistant Plasmodium
vivax in areas where P. falciparum and P. vivax co-exist is not entirely clear.
We examined the prevalence and extent of point mutations in pvdhfr and pvdhps in
70 P. vivax isolates from China, East Timor, Papua New Guinea (PNG), Philippines,
Vanuatu, and Vietnam. Mutations in seven codon positions were found in pvdhfr,
with the majority of isolates having double mutations (S58R/S117N). The greatest
range of mutations was observed in the PNG and Vanuatu isolates, ranging from
single to quadruple mutations (F57L/S58R/T61M/S117T). Single mutations in pvdhps
were observed only in parasites with mutations in corresponding pvdhfr. Parasites
with the S58R/S117N dhfr allelic type showed an MIC level for pyrimethamine and
cycloguanil comparable to that previously reported, but were susceptible to
WR99210.
PMID- 17038683
TI - Burden of malaria at community level in children less than 5 years of age in
Togo.
AB - A community-based baseline cross-sectional survey was conducted in three
districts in Togo in September 2004 as part of a multidisciplinary evaluation of
the impact of the Togo National Integrated Child Health Campaign. During this
campaign, long-lasting-insecticide-treated bed nets (LLITNs) were distributed to
households with children between 9 months and 5 years of age throughout the
country in December 2004. The pre-intervention survey provided baseline malaria
and anemia prevalence in children < 5 years of age during peak malaria
transmission. Of 2,532 enrolled children from 1,740 households, 62.2%
(1,352/2,172) were parasitemic and 84.4% (2,129/2,524) were anemic (hemoglobin <
11 g/dL). Moderate-to-severe anemia (< 8.0 g/dL) was found in 21.7% (543/2,524),
with a peak prevalence in children 6-17 months of age and was strongly correlated
with parasitemia (OR = 2.3, 95% CI: 1.8-2.5). Net ownership (mainly untreated)
was 225/2,532 (8.9%). Subsequent nation-wide introduction of LLITNs and the
introduction of artemisinin-based combination therapy have the potential to
markedly reduce this burden of malaria.
PMID- 17038684
TI - A randomized trial of artesunate-sulfamethoxypyrazine-pyrimethamine versus
artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum
malaria in Mali.
AB - The choice of artemisinin-based combination that is being adopted for malaria
treatment in sub-Saharan Africa may depend on several factors, including cost,
efficacy, side effects, and simplicity of administration. We tested the
hypothesis that artesunate-sulfamethoxypyrazine-pyrimethamine is as efficacious
as the four-dose regimen of artemether-lumefantrine for treatment of Plasmodium
falciparum malaria. The study was carried out during two transmission seasons
(2003 and 2004) in Sotuba, Mali. Participants at least 6 months of age with
uncomplicated P. falciparum malaria were randomly assigned to receive artesunate
sulfamethoxypyrazine-pyrimethamine or artemether-lumefantrine. Treatment efficacy
was assessed using the World Health Organization 28-day protocol. A total of 606
(303 in each arm) patients were enrolled. The cure rate was higher for artesunate
sulfamethoxypyrazine-pyrimethamine than for artemether-lumefantrine (98.7% versus
89.6%; P < 0.0001). After correction for cases of re-infection, the cure rates
were 100% and 99.0%, respectively (P = 0.08). No serious adverse events occurred.
Artesunate-sulfamethoxypyrazine-pyrimethamine is well-tolerated and effective
against P. falciparum malaria. It showed an additional benefit of preventing new
infections.
PMID- 17038685
TI - In vitro activity of artemisone compared with artesunate against Plasmodium
falciparum.
AB - Artemisinins show the potential for neurotoxicity in preclinical studies.
Artemisone is a leading candidate of second-generation semi-synthetic artemisinin
derivatives for antimalarial therapy devoid of neurotoxicity. Artemisone showed 3
5-fold higher in vitro activity (50% effective concentration (EC50) = 0.14
nmol/L, EC90 = 2.55 nmol/L) than artesunate against fresh Plasmodium falciparum
isolates from Gabon and a high-activity correlation indicates a shared drug
target.
PMID- 17038686
TI - Use of area under the curve to characterize transmission potential after
antimalarial treatment.
AB - To evaluate transmission potential of Plasmodium falciparum, we use the area
under the curve (AUC) of gametocyte levels after treatment as an approach to
combine their duration and magnitude. Analysis of determinants of AUC was based
on two main exposures: parasite clearance time (PCT) and presence of
dihydrofolate reductase and dihydropteroate synthase mutations associated with
sulfadoxine-pyrimethamine (SP) resistance in vitro. Exposures were determined
based on the first three days after treatment with SP of 96 individuals who had
malaria, cleared parasitemia by days 1-3, and were followed-up for 21 days. Using
regression methods, we characterized both the heterogeneity of the presence of
gametocytes (AUC > 0) and the magnitude of the AUC among those with an AUC > 0. A
PCT of two or three days was associated with a substantial and highly significant
odds ratio for presence of gametocytes. Among those who developed gametocytes, if
their clearance time was 3 days or if they had any mutations (1 or 2) the
magnitude of gametocytemia was > or = 3-fold. Methods presented are applicable to
both observational studies and clinical trials assessing the effect of therapies
on transmission potential.
PMID- 17038687
TI - Therapeutic efficacy of quinine plus sulfadoxine-pyremethamine for the treatment
of uncomplicated falciparum malaria in Bangladesh.
AB - In terms of drug resistance Bangladesh acts as an important gateway to the Indian
Subcontinent. However, little is known about the current status of drug
resistance in this country. The aim of this study was therefore to determine the
therapeutic efficacy as well as in vitro drug sensitivity of quinine for 3 days
plus a single dose of sulfadoxine/pyrimethamine (Q3F), an affordable alternative
to the previously used chloroquine, for the treatment of uncomplicated falciparum
malaria. Sixty-three patients were enrolled in the study; the overall cure rate
in a 42-day follow-up after PCR adjustment was 87.3% (95% CI: 77.6-94.1). One
patient was classified as early treatment failure (1.7%, 95% CI: 0.0-8.9%); 6
patients (10%; 95% CI: 3.8-20.5%) had late treatment failures within a median
time of 27 days. HRP2 in vitro drug sensitivity tests were performed on all
samples. Significantly higher (P = 0.008) in vitro IC(50)s for pyrimethamine in
treatment failures reflect the somewhat compromised drug sensitivity to this
drug. These data suggest that the combination of 3 days of quinine with a single
dose of sulfadoxine/pyrimethamine is an interesting and affordable alternative as
long as or whenever ACT is not available.
PMID- 17038688
TI - Successful integration of insecticide-treated bed net distribution with mass drug
administration in Central Nigeria.
AB - In Africa anopheline mosquitoes transmit malaria and lymphatic filariasis (LF);
insecticide-treated bed nets significantly reduce transmission of both.
Insecticide-treated bed net provision to children under 5 (U5) and pregnant women
(PW) is a major goal of malaria control initiatives, but use in Africa remains
low because of cost and logistics. We therefore integrated insecticide-treated
bed net distribution with the 2004 LF/onchocerciasis mass drug administration
(MDA) program in Central Nigeria. Community volunteers distributed 38,600
insecticide-treated bed nets, while simultaneously treating 150,800 persons with
ivermectin/albendazole (compared with 135,600 in 2003). This was subsequently
assessed with a 30-cluster survey. Among surveyed households containing U5/PW,
80% (95% CI, 72-87%) owned > or = 1 insecticide-treated bed net, a 9-fold
increase from 2003. This first linkage of insecticide-treated bed net
distribution with mass drug administration resulted in substantial improvement in
insecticide-treated bed net ownership and usage, without adversely affecting mass
drug administration coverage. Such integration allowed two programs to share
resources while realizing mutual benefit, and is one model for rapidly improving
insecticide-treated bed net coverage objectives.
PMID- 17038689
TI - Multilocus enzyme electrophoresis supports speciation within the Anopheles nili
group of malaria vectors in Cameroon.
AB - Multilocus enzyme analysis of the genetic variability and population structure
was conducted among three malaria vector species of the Anopheles nili group in
Cameroon: An. nili, An. carnevalei, and the recently described An. ovengensis. We
detected species-specific alleles and large differences in shared allele
frequencies at six of nine loci (e.g., PGM, GOT1, IDH1, IDH2, PGI, and alpha
GPD). This non-random distribution of alleles leads to high and significant
values of differentiation indexes (0.569 < Fst < 0.874, P < 10(-4)). These
results fully agree with standard morphologic descriptions, and therefore provide
further support for recent taxonomic classification within the An. nili group.
PMID- 17038690
TI - Experimental infection of Culex annulirostris, Culex gelidus, and Aedes vigilax
with a yellow fever/Japanese encephalitis virus vaccine chimera (ChimeriVax-JE).
AB - Australian mosquitoes from which Japanese encephalitis virus (JEV) has been
recovered (Culex annulirostris, Culex gelidus, and Aedes vigilax) were assessed
for their ability to be infected with the ChimeriVax-JE vaccine, with yellow
fever vaccine virus 17D (YF 17D) from which the backbone of ChimeriVax-JE vaccine
is derived and with JEV-Nakayama. None of the mosquitoes became infected after
being fed orally with 6.1 log(10) plaque-forming units (PFU)/mL of ChimeriVax-JE
vaccine, which is greater than the peak viremia in vaccinees (mean peak viremia =
4.8 PFU/mL, range = 0-30 PFU/mL of 0.9 days mean duration, range = 0-11 days).
Some members of all three species of mosquito became infected when fed on JEV
Nakayama, but only Ae. vigilax was infected when fed on YF 17D. The results
suggest that none of these three species of mosquito are likely to set up
secondary cycles of transmission of ChimeriVax-JE in Australia after feeding on a
viremic vaccinee.
PMID- 17038691
TI - Natural Anaplasma phagocytophilum infection of ticks and rodents from a forest
area of Jilin Province, China.
AB - Polymerase chain reaction integrated with sequence analysis was carried out to
investigate the natural Anaplasma phagocytophilum infection in ticks and rodents
from a forest area of Jilin Province, China. Four (4.0%) of 100 Ixodes
persulcatus and 2 (0.7%) of 286 Dermacentor silvarum ticks collected by flagging
vegetation were positive. Nine (8.8%) of 102 rodents were infected, as well as 2
(2.8%) of 71 I. persulcatus parasitizing on 25 rodents. The nucleotide sequences
of 1442-bp A. phagocytophilum 16S rRNA gene amplified from rodents and ticks were
identical to each other and to that previously reported in Heilongjiang Province
of China (GenBank accession no. AF205140), but different from those of other
countries. The sequences of 357-bp partial citrate synthase gene from the above
specimens were homologic, and varied from known A. phagocytophilum agents. These
findings add new information on the ecologic features of A. phagocytophilum and
indicate the threat of anaplasmosis in the area.
PMID- 17038692
TI - Spatial patterns of Lyme disease risk in California based on disease incidence
data and modeling of vector-tick exposure.
AB - Ixodes pacificus, particularly the nymphal life stage, is the primary vector to
humans of the Lyme disease agent Borrelia burgdorferi in California. During 2004,
we collected I. pacificus nymphs from 78 woodland sites in ecologically diverse
Mendocino County, which has a moderately high incidence of Lyme disease. Within
this county, nymphal density was elevated in forested areas with a growing degree
day range of 2,600-3,000 (10 degrees C base). Using a geographic information
systems approach, we identified all areas in California sharing these
environmental characteristics and thus projected to pose high acarologic risk of
exposure to host-seeking nymphal ticks. Such areas were most commonly detected in
the northwestern part of the state and along the Sierra Nevada foothills in the
northeast, but the analysis also identified isolated areas with high acarologic
risk in southern California. This mirrors the spatial distribution of endemic
Lyme disease during 1993-2005; most cases occurred in counties to the northwest
(58%) or northeast (26%), whereas fewer cases were reported from southern
California (16%). Southern zip-codes from which Lyme disease cases had been
reported were commonly located in close proximity to areas with high projected
acarologic risk. Overall, Lyme disease incidence in zip code areas containing
habitat with high projected acarologic risk was 10-fold higher than in zip code
areas lacking such habitat and 27 times higher than for zip code areas without
this habitat type within 50 km. A comparison of spatial Lyme disease incidence
patterns based on county versus zip code units showed that calculating and
displaying disease incidence at the zip code scale is a useful method to detect
small, isolated areas with elevated disease risk that otherwise may go
undetected.
PMID- 17038693
TI - Disruption of the salivary protein 14 in Ixodes scapularis nymphs and impact on
pathogen acquisition.
AB - We previously examined the physiological role of the anticoagulant salivary
protein 14 (salp14) in adult Ixodes scapularis and showed that Salp14 played a
role in tick feeding and engorgement. We now analyze whether the disruption of
the salp14 family expression by RNA interference affects tick weight in naive
nymph I. scapularis. Salp14 expression after dsRNA injection was significantly
reduced, as shown by mRNA and protein analysis. However, nymph engorgement weight
was not altered in salp9pac (salp14 paralog) dsRNA-injected ticks. We also
determined Borrelia burgdorferi and Anaplasma phagocytophilum acquisition in I.
scapularis nymphs that had reduced Salp14 expression. B. burgdorferi and A.
phagocytophilum acquisition was not affected 72 hours after feeding. Our results
suggest that different mechanisms govern nymph and adult feeding in I.
scapularis.
PMID- 17038694
TI - Scabies mite inactivated serine protease paralogues are present both internally
in the mite gut and externally in feces.
AB - The scabies mite, Sarcoptes scabiei, is the causative agent of scabies, a disease
that is common among disadvantaged populations and facilitates streptococcal
infections with serious sequelae. Previously, we encountered large families of
genes encoding paralogues of house dust mite protease allergens with their
catalytic sites inactivated by mutation (scabies mite inactivated protease
paralogues [SMIPPs]). We postulated that SMIPPs have evolved as an adaptation to
the parasitic lifestyle of the scabies mite, functioning as competitive
inhibitors of proteases involved in the host-parasite interaction. To propose
testable hypotheses for their functions, it is essential to know their locations
in the mite. Here we show by immunohistochemistry that SMIPPs exist in two
compartments: 1) internal to the mite in the gut and 2) external to the mite
after excretion from the gut in scybala (fecal pellets). SMIPPs may well function
in both of these compartments to evade host proteases.
PMID- 17038695
TI - West Nile virus quantification in feces of experimentally infected American and
fish crows.
AB - To better understand the potential environmental health risk presented by West
Nile virus (WNV)-contaminated feces, we quantified the amount of WNV present in
the feces of experimentally infected American crows (Corvus brachyrhynchos) and
fish crows (Corvus ossifragus). Peak fecal titers ranged from 10(3.5) to 10(8.8)
plaque-forming units (PFU)/g for 10 American crows and from 10(2.3) to 10(6.4)
PFU/g for 10 fish crows. The presence of infectious WNV in bird feces indicates a
potential for direct transmission of WNV. Thus, handlers of sick or dead birds
should take appropriate precautions to avoid exposure to fecal material.
PMID- 17038696
TI - West Nile virus infection of primary mouse neuronal and neuroglial cells: the
role of astrocytes in chronic infection.
AB - Primary cultures of embryonic murine neurons and newborn mouse astrocytes were
inoculated with West Nile virus (WNV) strain NY385-99 to compare the pathogenesis
of WNV infection in these types of CNS cells. Two different outcomes were
observed. WNV infection in the neurons was rapidly progressive and destructive;
within 5 days, all of the neurons were destroyed through apoptosis. WNV infection
in the astrocytes evolved more slowly and did not seem to be highly lethal to the
cells. The infected astrocytes continued to produce infectious virus (10(4.6)
10(6.5) PFU/mL) for 114 days, in a permissive, persistent infection. During this
period, WNV antigen could be shown in the cytoplasm of the infected astrocytes by
immunocytochemical assay, transmission electron microscopy of ultrathin sections,
and in the cell culture medium by complement fixation test. Our results with this
in vitro experimental murine cell model indicate that astrocytes can develop
chronic or persistent infection with WNV, suggesting that these cells may play a
role in the maintenance of WNV in the CNS.
PMID- 17038697
TI - Experimental infection of fox squirrels (Sciurus niger) with West Nile virus.
AB - Tree squirrels (Sciurus spp.) have exhibited high seroprevalence rates,
suggesting that they are commonly exposed to West Nile virus (WNV). Many
characteristics of WNV infections in tree squirrels, such as the durations and
levels of viremia, remain unknown. To better understand WNV infections in fox
squirrels (S. niger), we subcutaneously inoculated fourteen fox squirrels with
WNV. Peak viremias ranged from 10(4.00) plaque-forming units (PFU)/mL of serum on
day 2 post-infection (DPI) to 10(4.98) PFU/mL on 3 DPI, although viremias varied
between individuals. Oral secretions of some fox squirrels were positive for WNV
viral RNA, occasionally to moderate levels (10(3.2) PFU equivalent/swab). WNV PFU
equivalents in organs were low or undetectable on 12 DPI; gross and histologic
lesions were rare. The viremia profiles of fox squirrels indicate that they could
serve as amplifying hosts in nature. In addition, viral RNA in the oral cavity
and feces indicate that this species could contribute to alternative WNV
transmission in suburban communities.
PMID- 17038698
TI - Pseudotyped viruses permit rapid detection of neutralizing antibodies in human
and equine serum against Venezuelan equine encephalitis virus.
AB - Virus envelope proteins are the primary targets of neutralizing antibody
responses. The epitopes recognized differ sufficiently between virus subtypes and
species to distinguish viruses and provide an important basis for disease
diagnosis. Venezuelan equine encephalitis virus (VEEV) causes acute febrile
illness in humans and has high mortality in equines. The most specific detection
methods for serum antibodies use live virus in neutralization assays or in
blocking enzyme linked immunosorbent assays. However, work with Venezuelan equine
encephalitis virus requires biosafety level 3 containment and select agent
security in the United States. We report two new assays for detection of
Venezuelan equine encephalitis virus neutralizing antibody responses, based on
virus pseudotypes. The first provides detection by marker gene expression after
20 hours and is particularly suited for high-throughput screening; the second
uses a new, rapid virus entry assay to give readouts within 1 hour. Both assays
are safe, sensitive, and in general recapitulate neutralizing antibody titers
obtained by conventional plaque reduction assays. Each is suitable as a rapid
primary screen for detection of neutralizing antibodies against Venezuelan equine
encephalitis virus.
PMID- 17038699
TI - Molecular epidemiology of dengue type 3 virus in Brazil and Paraguay, 2002-2004.
AB - We studied the molecular epidemiology of dengue virus type 3 (DENV-3) in Brazil
and Paraguay by analyzing the 5' and 3' untranslated regions (5' and 3'UTRs) and
the E protein gene of viruses isolated between 2002 and 2004. Both 5' and 3'UTRs
were highly conserved. However, the 3'UTR of two isolates from Brazil contained
eight nucleotide deletions compared with the remaining 26 viruses. Phylogenetic
analyses suggested that DENV-3 was introduced into Brazil from the Caribbean
Islands at least twice and into Paraguay from Brazil at least three times.
PMID- 17038700
TI - Exposure to human respiratory viruses among urban performing monkeys in
Indonesia.
AB - Performing monkeys, a common phenomena in Asia, occupy a unique urban niche that
comprises a number of factors influencing the likelihood of cross-species
transmission of pathogens. Here we present the first documented evidence of
exposure to measles, rubella, and parainfluenza in a population of performing
monkeys. Evidence of exposure to these endemic human respiratory viruses in the
performing monkeys confirms human-to-primate transmission and suggests the
possibility of primate-to-human transmission. Urban animal markets, the likely
source of these performing monkeys, may represent an environment conducive to the
mixing of animals and pathogens, making these monkeys a potential conduit for
infectious agents passing from a variety of animals found in animal markets to
humans. The potential significance of these results to human public health and
the unique contexts of disease transmission associated with the urban ecology of
the performance monkeys are discussed. Given the level of overseas travel, this
potential threat is not confined solely to Asia.
PMID- 17038701
TI - Pro-inflammatory cytokines and C-reactive protein are associated with
undernutrition in the context of Schistosoma japonicum infection.
AB - Schistosomiasis is associated with undernutrition, but the mechanisms involved
remain unknown. We analyzed baseline and follow-up data from a longitudinal
treatment-reinfection study in N = 477 Schistosoma japonicum-infected subjects 7
20 years of age from Leyte, the Philippines. After baseline treatment with
praziquantel, follow-up visits were scheduled every 3 months for 18 months;
stool, venous blood, and anthropometric measurements were collected at each
visit. Cytokine production by peripheral blood mononuclear cells (PBMCs)
stimulated with specific S. japonicum antigens was measured once 4 weeks after
treatment. After adjustment for confounders, S. japonicum intensity was
associated with decreased serum albumin and Z-scores (all P < 0.05) and with
increased serum C-reactive protein (CRP) and interleukin (IL)-6. CRP was
associated with decreased albumin and Z-scores (all P < 0.01). Production of IL
1b and tumor necrosis factor (TNF)-alpha in response to worm antigen was
associated with decreased albumin (both P < 0.005) and height-for-age Z-score
(TNF-alpha only, P = 0.05). S. japonicum-associated undernutrition may, in part,
result directly from inflammation.
PMID- 17038703
TI - Isolation of Rickettsia akari from eschars of patients with rickettsialpox.
AB - Rickettsialpox is a cosmopolitan, mite-borne, spotted fever rickettsiosis caused
by Rickettsia akari. The disease is characterized by a primary eschar, fever, and
a papulovesicular rash. Rickettsialpox was first identified in New York City in
1946 and the preponderance of recognized cases in the United States continues to
originate from this large metropolitan center. The most recently isolated U.S.
strain of R. akari was obtained more than a half century ago. We describe the
culture and initial characterization of five contemporaneous isolates of R. akari
obtained from eschar biopsy specimens from New York City patients with
rickettsialpox. This work emphasizes the importance and utility of culture-and
molecular-based methods for the diagnosis of rickettsialpox and other eschar
associated illnesses.
PMID- 17038702
TI - Molecular detection of Rickettsia felis, Rickettsia typhi and two genotypes
closely related to Bartonella elizabethae.
AB - A total of 56 fleas were collected from mice, rats, and one hedgehog in national
parks of mainland Portugal and the Madeira Island. All fleas were tested for the
presence of bacteria of the genera Rickettsia and Bartonella using PCR assays. In
fleas from mainland Portugal, we detected Rickettsia felis in one Archaeopsylla
erinacei maura flea and in one Ctenophtalmus sp. In five Leptopsylla segnis fleas
taken from rats in the Madeira Island, we identified Rickettsia typhi. In
addition, in four fleas from the genera Ornithophaga and Stenoponia collect from
mice and a rat in mainland Portugal, we detected the presence of two new
Bartonella genotypes closely related to Bartonella elizabethae. Our findings
emphasize the potential risk of flea-transmitted infections in mainland Portugal
and the Madeira archipelago, and extend our knowledge of the potential flea
vectors of human pathogens.
PMID- 17038704
TI - Immunologic tests in patients after clinical cure of visceral leishmaniasis.
AB - The results of five serologic tests (ELISA using promastigote antigen [ELISAp]
and recombinant K39 [ELISArK39] and K26 [ELISArK26] antigens, indirect
immunofluorescence test using promastigote antigen [IIFT], and
immunochromatographic tests using the rK39 antigen [TRALd]) and of the Montenegro
skin test (MST) were analyzed in 41 individuals treated for kala-azar and living
in Porteirinha, Minas Gerais, Brazil. The tests were carried out 1 week to 12
years after specific treatment. All MSTs during the 8 months after treatment were
negative, whereas after 1 year, 28 (84.8%) were positive. Negativity in all
serologic tests was observed for 11 (26.8%) of the 41 individuals, whereas
positivity in at least one test was observed for 70.3% of subjects evaluated > or
= 2 years after treatment. With respect to each exam, positivity was 38.0% for
TRALd, 61.9% for ELISA rK39, 47.6% for ELISA rK26, 38.0% for ELISAp, and 40.5%
for IIFT. None of the individuals presented recurrence of the disease during the
4 years of follow-up. The tests were repeated in 24 of the 41 individuals, after
some time, and the results were the same in 33.3% of the cases. We conclude that
serological tests for kala-azar might continue to be positive after treatment of
the disease, although this does not indicate a poor prognosis or a poor
therapeutic response.
PMID- 17038705
TI - Loss of leishmanin skin test antigen sensitivity and potency in a longitudinal
study of visceral leishmaniasis in Bangladesh.
AB - Annual leishmanin skin test (LST) surveys were conducted in a visceral
leishmaniasis-endemic Bangladeshi community from 2002 through 2004, using
Leishmania infantum antigen from the same manufacturer and batch. In 2002, 530
(35%) of 1,532 had positive LST results; the prevalence increased with increasing
age. The LST result was positive in 24 (51%) of 47, 18 (72%) of 25, and 11 (85%)
of 13 kala-azar patients treated in the previous 1-11, 12-23, and 24-35 months. A
positive LST result in 2002 was associated with protection against subsequent
kala-azar (P < 0.0001). In 2003-2004, decreased antigen sensitivity was observed.
Among 686 participants, 34% were LST-positive in 2002, 29% in 2003, and 19% in
2004. Of 63 cured kala-azar patients, 70% were positive in 2002, 53% in 2003, and
only 30% in 2004. Among 171 participants tested with both antigens, L. infantum
study antigen sensitivity was 70% compared with L. amazonensis antigen. Our data
underscore the need for better production, standardization, and documentation of
sensitivity, potency, and stability of leishmanin antigens.
PMID- 17038706
TI - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces Leishmania major burdens in
C57BL/6 mice.
AB - Acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can suppress
adaptive immunity. In this study, pre-exposure of Leishmania major-infected mice
to TCDD caused a dose-dependent and unexpected decrease in parasite burdens on
day 20 after infection. In contrast, TCDD-mediated lymphoid atrophy, suppressed
antibody levels, and enhanced interleukin-2 production were observed as expected.
These results suggest that TCDD may enhance resistance to L. major in the face of
immune suppression.
PMID- 17038707
TI - A prospective study of the effects of sustained vector surveillance following
community-wide insecticide application on Trypanosoma cruzi infection of dogs and
cats in rural Northwestern Argentina.
AB - Domestic dogs were used as natural sentinels to assess prospectively the long
term impact of selective, community-based spraying with pyrethroid insecticides
after community-wide spraying on transmission of Trypanosoma cruzi in rural
villages under surveillance between 1992 and 2002. In 2000 and 2002 light
infestations by Triatoma infestans were recorded, and 523 dogs and cats were
examined serologically or by xenodiagnosis. The prevalence of T. cruzi infection
in dogs decreased from 65% at baseline to 8.9% and 4.7% at 7.5 and 10 years after
sustained vector surveillance, respectively. The average annual force of
infection dropped 260-fold from 72.7 per 100 dog-years at baseline to <0.3% in
2002, as determined prospectively and retrospectively from the age-prevalence
curve of native dogs born during surveillance. Multiple logistic regression
analysis showed that prevalent cases in dogs in 2000 and 2002 were associated
positively and significantly with the peak number of T. infestans caught in
domestic areas at the dog's compound during its lifetime. The sustained decline
in T. cruzi infections in dogs and cats is the result of selective, community
based insecticide spraying that kept the abundance of infected T. infestans at
marginal levels, fast host population turnover, and low immigration rates from
areas with active transmission.
PMID- 17038708
TI - Incidence, etiology, and impact of diarrhea among deployed US military personnel
in support of Operation Iraqi Freedom and Operation Enduring Freedom.
AB - A health assessment survey was collected from US military personnel deployed to
the Middle East taking part in the "Rest and Recuperation" program or on
temporary assignment to Camp As Sayliyah Doha, Qatar, from January to December
2004. In addition, a concurrent clinic-based observational study was conducted to
determine pathogen etiology and potential risk factors. From 28,322 health
assessment surveys, overall self-reported incidence of diarrhea was 4.9 cases per
100 person-months. Disease incidence increased with rank and was higher in Iraq
compared with Afghanistan. During this period, 109 US military personnel with
acute diarrhea and 85 asymptomatic personnel were enrolled in the observational
study. Enterotoxigenic E. coli (ETEC) was the predominant pathogen (32%),
followed by enteroaggregative E. coli (12%) and Salmonella spp. (6%). These data
are consistent with previous reports implicating ETEC as the primary cause of
acute diarrhea for military personnel deployed to this region.
PMID- 17038709
TI - BCG vaccine effectiveness against Buruli ulcer: a case-control study in Benin.
AB - BCG remains the only possible prophylactic intervention against Buruli ulcer
(BU). Estimating its public health impact on BU control is an important issue. We
conducted a case-control study to investigate the vaccine effectiveness of
routine BCG vaccine against BU in southern Benin. From August 2002 to August
2003, BCG vaccination status was obtained for 279 clinically diagnosed BU cases
and 988 age- and sex-matched neighborhood controls. BCG coverage, which was
estimated by the presence of a scar or a vaccination record, was 64.5% in cases
and 67.2% in controls. There was no evidence of a protective effect of routine
BCG vaccination against BU in southern Benin (vaccine effectiveness adjusted for
socioeconomic status = 12%, 95% confidence interval = -24% to 37%).
PMID- 17038710
TI - Bone health in children.
PMID- 17038711
TI - Prevention of diabetes.
PMID- 17038712
TI - X ray imaging goes digital.
PMID- 17038713
TI - Preoperative staging for rectal cancer.
PMID- 17038714
TI - Use of mobile phones in hospitals.
PMID- 17038717
TI - UN questions China over organ harvesting.
PMID- 17038718
TI - Dutch clinic is ordered to stop giving stem cell therapy.
PMID- 17038719
TI - The importance of smelly feet and stinky cheese.
PMID- 17038721
TI - New York plans to restrict trans fats in restaurants.
PMID- 17038723
TI - Guideline calls for better treatment of atrial fibrillation.
PMID- 17038726
TI - Failure to control mosquitoes has led to two fever epidemics in India.
PMID- 17038730
TI - Doctors in Germany protest at a new restrictive law on tissue banks.
PMID- 17038731
TI - NICE says anti-dementia drugs should be used only for moderate Alzheimer's
disease.
PMID- 17038732
TI - South Africa sidelines its health minister on AIDS issues.
PMID- 17038733
TI - Ignorance about HIV is still high in many parts of Europe.
PMID- 17038735
TI - Epileptic seizures can follow high doses of oral vardenafil.
PMID- 17038736
TI - Acute renal failure.
PMID- 17038737
TI - Investigating iron status in microcytic anaemia.
PMID- 17038738
TI - ABC of obesity. Management: part II--drugs.
PMID- 17038739
TI - NHS maternity units should not encourage commercial banking of umbilical cord
blood.
PMID- 17038740
TI - How to formulate research recommendations.
PMID- 17038742
TI - Parachute approach to evidence based medicine: arguments are easily refuted.
PMID- 17038743
TI - Parachute approach to evidence based medicine: as obvious as ABC.
PMID- 17038744
TI - MRI in predicting curative resection of rectal cancer: defining a "window of
opportunity" for laparoscopic surgery.
PMID- 17038745
TI - MRI in predicting curative resection of rectal cancer: does post-neoadjuvant MRI
have a role?
PMID- 17038746
TI - MRI in predicting curative resection of rectal cancer: new dilemma in
multidisciplinary team management.
PMID- 17038747
TI - Belittlement and harassment of medical students: remedial training--ethics and
sensitivity.
PMID- 17038748
TI - Belittlement and harassment of medical students: is a source of medical
education.
PMID- 17038749
TI - Obesity is a wake up call for developing world too.
PMID- 17038750
TI - Diagramming qualitative theories.
PMID- 17038751
TI - Continuities and discontinuities in the experiences of felt and enacted stigma
among women with HIV/AIDS.
AB - In the post-1996 era, the effectiveness of antiviral therapies (such as highly
active antiretroviral therapy [HAART]), which transformed HIV/AIDS into a more
manageable disease, raised expectations that the disease's stigma would decrease.
The authors compared focused-interview data from a pre-HAART (1994 to 1996) and a
HAART-era (2000 to 2003) sample of African American, Puerto Rican, and White
women living with HIV/AIDS to identify changes in stigma experiences and suggest
reasons for continued stigmatization. In both eras, general stereotypes about
HIV/AIDS, as well as gender- and race-related stereotypes about the disease, were
identified. Internalizing any of these stereotypes was a necessary and sufficient
condition for feeling stigmatized. Instances of enacted stigmatization were more
frequent and intense in the pre-HAART era. Nevertheless, misinformation and
irrational fears of contagion, which triggered stigmatizing behavior, persisted
into the HAART era. This analysis revealed that although enacted stigmatization
has decreased slightly, felt stigma remains a primary adaptational challenge
facing women with HIV/AIDS.
PMID- 17038752
TI - "Never again" stories of nurses: dilemmas in nursing practice.
AB - The authors describe significant turning points immanent in "never again" stories
that practicing nurses, having participated in previously, vowed not to allow to
recur during future, similar situations. Nurses submitted written accounts of
critical, "never again" situations. The authors used critical incident technique
and employed Colaizzi's approach to reveal the essential structure. Patient
outcomes were fatal, close calls, dehumanizing, or isolating. Never again stories
incorporated ethical dilemmas, deficits in nurses' knowledge, lack of confidence
in clinical abilities, and failure to act correctly. Patients' welfare was the
center of accounts. Circumstances threatened patients' and family members' trust
in nurses and other providers. Patients' wishes were denied because of haste,
providers' arrogance, or providers' desire not to be inconvenienced. Nurses'
emotions mirrored a sense of failed responsibility for patients. Regret was
tempered by nurses' pledges. Critical incidents revealed dilemmas in which
nurses' autonomous clinical practice was constrained by feelings of
powerlessness.
PMID- 17038753
TI - "Pull yourself up by your bootstraps": a response to depression in older adults.
AB - Although depression is one of the most common problems among adults in primary
care settings, many do not seek or adhere to the treatment regimens suggested by
their providers. Understanding the cultural model surrounding depression and its
treatment in older adults might provide insight into the development of more
effective strategies for addressing the problem in the clinical setting. In this
study, the authors conducted semi-structured interviews with adults over age 65.
Personal responsibility for the management of depression emerged as a pervasive
approach to dealing with depression. Older adults used orientational and movement
metaphors to describe the process of moving out of depression. They viewed
initiation and follow-through of this process as the sole responsibility of the
depressed individual. This attitude might be rooted in the cultural experiences
of this particular cohort of older adults and has implications for their use of
physical and mental health services for depression.
PMID- 17038754
TI - A contextual study of daily living strategies in neurocognitively impaired adults
with schizophrenia.
AB - Schizophrenia is a severe mental illness often recognized as a degenerative
neurocognitive condition. For some with the disorder, the impairment is fairly
mild, but for others, neurocognitive abilities can be severely compromised. In
this study, 5 individuals with schizophrenia had been assessed through a
laboratory-based neurocognitive battery as having severe impairment. Their
neurocognitive status was unknown to the author, and she was able to observe
daily tasks and ask questions about strategies they employed while completing
tasks, and analyze the data without preconceptions about their status. This study
was guided by notions of ecological validity, which is the comparison between lab
tests and real-world functioning. Despite their cognitive deficits, these
individuals had remarkable strengths, which included drawing supportive people
into their worlds to fulfill their daily tasks. These data contribute to the
rehabilitation literature and propose remedies for struggles of daily living when
one has schizophrenia.
PMID- 17038755
TI - Power imbalance and consumerism in the doctor-patient relationship: health care
providers' experiences of patient encounters in a rural district in India.
AB - The aim of this study is to explore health care providers' experiences and
perceptions of their encounters with male and female patients in a rural district
in India with special reference to tuberculosis (TB) care. The authors conducted
semistructured interviews with 22 health care providers, 17 men and 5 women, from
the public and private health care sectors. Findings reveal that doctors adopted
an authoritarian as well as a consumerist approach in the medical encounter,
indicating that power imbalances in the doctor-patient relationship are
negotiable and subject to change. Gender was identified as an influencing factor
of the doctor's dominance. A patient-centered approach, acknowledging patients'
own experiences and shared decision making, is called for and should be included
in TB control activities. This seems to be especially important for female
patients, whose voices were not heard in the medical encounter.
PMID- 17038756
TI - "I thought there was no hope for me": a behavioral intervention for urban mothers
with problem drinking.
AB - In this article, the authors evaluate the effects of a behavioral intervention
for mothers with problem drinking who were infected with, or at risk for, HIV.
They randomly selected 25 mothers from a larger longitudinal randomized
controlled intervention trial for a qualitative interview. The authors found that
mothers' participation in the program was facilitated by the development of a
strong therapeutic alliance with the intervention facilitator and the use of a
harm reduction approach toward alcohol and/or drug abuse. Mothers also reported
that training in coping skills and the emphasis on parent-adolescent
relationships were beneficial for program engagement and behavior change. The
authors conclude from these results that treatment approaches that take into
account the complexity of urban mothers' lives and substance use patterns can
successfully engage and treat these women at high risk for adverse outcomes.
PMID- 17038758
TI - Managing shame and stigma: case studies of female carers of people with AIDS in
southern Thailand.
AB - The authors of this article discuss the effects of shame and stigma on female
caregivers of people living with AIDS in southern Thailand. They conducted a
longitudinal ethnographic case study over 8 months and collected data using
interviews, observations, field notes, and journaling. The authors performed
qualitative content analysis and narrative analysis. Public judgment was created
in a moral climate, framed by Buddhist precepts of correct and honorable
behavior, with different levels of tolerance and stigmatization between men and
women. Women caregivers engaged in concealing practices, deception, and
withdrawal from social relationships to manage the effects of shame and stigma.
PMID- 17038757
TI - Caught in a balancing act: parents' dilemmas regarding their ADHD child's
treatment with stimulant medication.
AB - The authors explored parents' perceptions of and everyday experiences with the
stimulant medication used to treat their child's attention deficit hyperactivity
disorder (ADHD) in this phenomenological study. They elicited experiences through
semistructured interviews with 10 Canadian parents of children with ADHD. In the
interviews, parents revealed the meaning the stimulant medication had taken on in
the context of their everyday lives. Through the interview analysis, dilemma
emerged as the dominant theme. Parents were caught in a dynamic balancing act, as
they considered the medication's desirable and undesirable effects in various
settings. In addition, parents shared their expectations regarding the
medication's role in their child's future. The study's findings reinforce the
necessity of further qualitative research in this area, given the growing number
of families around the globe whose children have been diagnosed with ADHD.
PMID- 17038759
TI - Orienting multiple interviewers: the use of an interview orientation and
standardized interview.
AB - An interviewer orientation protocol and standardized interview can be an
effective way of orienting multiple interviews to qualitative research. A
standardized interview involves an actor taught to portray a research participant
consistently in several interview encounters. In this article, the authors
describe the interview protocol, and the development and application of a
standardized interview. The benefits of using a standardized interview as a
formative method to orient multiple interviewers include assessing the
interviewers' integration of the interview protocol, the nonverbal and verbal
presentation of the interview process between interviewers, and the general flow
of the interview from interviewer to interviewer. As more qualitative research is
conducted using multiple interviewers, the method of an interview protocol and
subsequent standardized interview might be helpful when orienting interviewers to
the challenges and promises of conducting research using a critical framework.
PMID- 17038760
TI - Comparison of verbal claims for natural health products made by health food
stores staff versus pharmacists in Ontario, Canada.
AB - BACKGROUND: This study tested the hypothesis that while there are no written
medical claims existing for many NHP, such claims are made verbally, giving a
false impression that these are proven medical products. OBJECTIVE: To compare
the number and type of verbal claims for NHP made by pharmacists to those made by
health food stores personnel. METHODS: Randomly selected Canadian pharmacies
selling NHP and health food stores were visited and the staff was asked to
recommend natural health products for the treatment of hypertension. RESULTS: All
health food stores (n=20) but only 4 out of 38 pharmacies (p< 0.001) recommended
NHP for the treatment of hypertension. A majority of health food store staff
(70%) stated that NHP are superior or equal to medicinal drugs in treating
hypertension based on efficacy. CONCLUSION: Unlike pharmacy practice, verbal
claims are common practice in health food stores, despite the lack of either
written claims and/or proof of efficacy for most of them. These may be a very
effective approach given that 30-40% of North American adults are functionally
illiterate. These verbal claims are often inappropriate and not evidence-based.
PMID- 17038761
TI - Stabilization of the spark-discharge point on a sample surface by laser
irradiation for steel analysis.
AB - A combined technique with laser irradiation is suggested to control spark
discharge for analytical use, having a unique feature that firing points of the
spark discharge can be fixed by laser irradiation. Because the spark discharge
easily initiates at particular surface sites, such as non-metallic inclusions,
called selective discharge, the concentration of some elements sometimes deviates
from their average one in spark discharge optical emission spectrometry.
Therefore, stabilization of firing points on a sample surface could improve the
analytical precision.
PMID- 17038763
TI - Raman microspectroscopy/imaging study on phase-vanishing processes of fluorous
biphase systems in microchannel-microheater chips.
AB - Temperature-dependent phase-vanishing processes between perfluorohexane (FC-72)
and n-heptane (C7H16, volume ratio of 1:1 and phase-vanishing temperature>41
degrees C), were studied in a glass microchannel-microheater chip under solution
flow conditions. Without applying a voltage to the heater at 21 degrees C, the
two liquids in the microchannel were separated into two streams at a solution
flow rate (v) of 0.975 cm/s, while the phase boundary between FC-72 and C7H16
vanished in the downstream side of the heater at V=4.5 V. Then, we conducted
Raman intensity imaging during the phase vanishing processes in the microchannel
by monitoring the band at 756 (FC-72) or 1456 cm-1 (C7H16). At V=4.5 V and
v=0.975 cm/s, although no phase boundary between the two liquids in the
microchannel was observed, the relevant Raman intensity images indicated the
inhomogeneous nature of the solution, and distribution of C7H16 to the FC-72
phase along with solution flow was observed.
PMID- 17038762
TI - A disposable, screen-printed electrode for the amperometric determination of
azide based on the immobilization with catalase or tyrosinase.
AB - A disposable, screen-printed electrode based on the immobilization of catalase or
tyrosinase was developed to construct biosensors for the amperometric
determination of azide. The determination principles for azide by these two
methods are based on inhibiting the enzymatic consumption of an electrode
detectable substance (hydrogen peroxide or catechol) on an enzyme-immobilized
electrode. Both of these methods show a sensitive detection range and a short
measuring time.
PMID- 17038764
TI - Fluorescence lifetime imaging microscope consisting of a compact picosecond dye
laser and a gated charge-coupled device camera for applications to living cells.
AB - An inverted microscope was combined with a compact dye laser with a pulse width
of <190 ps and an intensified charge-coupled device (ICCD) camera with a minimum
gate width of 200 ps. The resulting fluorescence lifetime imaging microscope,
which has a temporal resolution of 340 ps, was used to measure the fluorescence
lifetime of polymer microspherers. The results indicated a fluorescence lifetime
of 0.9 ns. The present analytical instrument was also employed in an evaluation
of biological cells after labeling them with SYTO 13, a fluorescent dye.
PMID- 17038765
TI - Application of total reflection X-ray fluorescence spectrometry to small glass
fragments.
AB - Total reflection X-ray fluorescence spectrometry (TXRF) has been applied for
trace elemental analysis of small glass fragments. A small glass sample (a
fragment with weight less than 0.5 mg) was decomposed by 100 microg of HF/HNO3
acid; the material was condensed to 10 microl and was dried on a Si wafer. Since
the size of the dried residue on the Si wafer was less than 1 cm in diameter, an
incident X-ray beam with about 1 cm in width could effectively excite elemental
components in such a small glass fragment. The precision of the present technique
was checked by analyzing the glass fragments (<0.5 mg) from NIST SRM612; the
relative standard deviations (RSD) of less than 8.1% were achieved for elemental
ratios that were normalized by Sr. Fragments (<0.5 mg) obtained from 23 figured
sheet glasses were used as samples for estimating the utility of this technique
to forensic discrimination. Comparison of five elemental ratios of Ti/Sr, Mn/Sr,
Zn/Sr, Rb/Sr, and Pb/Sr calculated from X-ray fluorescence spectra was effective
in distinguishing glass fragments that could not be differentiated by their
refractive indexes (RI).
PMID- 17038766
TI - Interaction of [HgX4]2- with berberine by absorption and resonance Rayleigh
scattering spectra and their analytical applications.
AB - In a diluted H2SO4 solution, Hg(II) reacts with halide anions X- (including Cl-,
Br- and I-) to form anionic complexes [HgX4]2- that can further react with
berberine to form ion-association complexes of [Ber]2[HgX4]. As a result, the
absorption spectra change, their maximum absorption wavelengths are at 230 nm for
[Ber]2[HgCl4], 278 nm for [Ber]2[HgBr4] and 300 nm for [Ber]2[HgI4]. However,
among the three complexes, only [Ber]2[HgI4] can lead to distinctly enhanced
resonance Rayleigh scattering (RRS), and a new RRS spectrum appears. The maximum
RRS wavelength is located at 397 nm, and the RRS intensity is proportional to the
concentration of berberine in the range of 0-2.5 microg mL-1. The optimum
conditions, the influence factors for the reaction and the effects of coexisting
substances have been investigated. A new, simple and fast RRS method for the
determination of berberine based on the ion-association reaction of [HgI4]2- with
Ber+ was developed. The method has high sensitivity and good selectivity; the
detection limit for berberine (3 sigma/K) is 7.22 ng mL-1. The method can be
applied to the determination of berberine in some Chinese patent drug and the
extracts of Coptis Chinensis. Furthermore, the mechanism of the reaction and the
reasons for RRS enhancement have been discussed.
PMID- 17038767
TI - Multivariate analysis for 1H-NMR spectra of two hundred kinds of tea in the
world.
AB - NMR measurements coupled with pattern-recognition analysis offer a powerful
mixture-analysis tool for latent-feature extraction and sample classification. As
fundamental applications of this analysis for mixtures, the 1H spectra of 176
kinds of green, black, oolong and other tea infusions were acquired by a 500 MHz
NMR spectrometer. Each spectrum pattern was analyzed by a multivariate
statistical pattern-recognition method where Principal Component Analysis (PCA)
was used in combination with Soft Independent Modeling of Class Analogy (SIMCA).
SIMCA effectively selected variables that contribute to tea categorization. The
final PCA resulted in clear classification reflecting the fermentation and
processing of each tea, and revealed marker variables that include catechin and
theanine peaks.
PMID- 17038768
TI - Evaluation of the oxygen reduction activities of rare-earth oxide-supported
silver catalysts using a channel flow double electrode.
AB - The channel flow double electrode (CFDE) was used for the evaluation of the
oxygen reduction activities in alkaline solution of rare-earth oxide-supported
silver catalysts. The CFDE cell was modified for the experiment using the powder
catalyst as a working electrode. In the present experiment, the silver electrode
was supported with CeO2 in order to improve the performance of the oxygen
reduction. The detecting electrode current for HO2- emitted from the working
electrode was recorded simultaneously with the measurement of the i-E curve of
each working electrode. Moreover, the average number of charge transfers n was
calculated from the working and detecting electrode currents. The value of n for
the oxygen reduction was approximately 4 for silver electrode supported with rare
earth oxide, compared with the n value of pure silver that was smaller than 4. On
the basis of these results, the mechanisms of oxygen reduction on these
electrodes and role of the rare-earth oxide in alkaline solution were discussed.
PMID- 17038769
TI - Speciation of antimony by preconcentration of Sb(III) and Sb(V) in water samples
onto nanometer-size titanium dioxide and selective determination by flow
injection-hydride generation-atomic absorption spectrometry.
AB - A novel method for prevention of the oxidation of Sb(III) during sample
pretreatment, preconcentration of Sb(III) and Sb(V) with nanometer size titanium
dioxide (rutile) and speciation analysis of antimony, has been developed.
Antimony(III) could be selectively determined by flow injection-hydride
generation-atomic absorption spectrometry, coexisting with Sb(V). Trace Sb(III)
and Sb(V) were all adsorbed onto 50 m g TiO2 from 500 ml solution at pH 3.0
within 15 min, then eluted by 10 ml of 5 mol/l HCl solution. One eluent was
directly used for the analysis of Sb(III); to the other eluent was added 0.5 g KI
and 0.2 g thiourea to reduce Sb(V) to Sb(III), then the mixture was used for the
determination of total antimony. The antimony(V) content is the mathematical
difference of the two concentrations. Detection limits (based on 3sigma of the
blank determinations, n=11) of 0.05 ng/ml for Sb(III) and 0.06 ng/ml for Sb(V),
were obtained.
PMID- 17038770
TI - Determination of poly(3-hydroxybutyrate) using a combination of enzyme-based
biosensor and alkaline hydrolysis.
AB - The combination of an enzyme-based biosensor and alkaline hydrolysis was
developed for the measurement of poly(3-hydroxybutyrate) (PHB). The principle of
the determination is based on that the alkaline condition converts PHB to produce
its monomer, 3-hydroxybutyrate (3-HB), which generates a detectable current
signal by an amperometric biosensor through coupled two-enzyme reactions on an
electrode. This method takes less than 40 min, and results in a linear detection
range of 0.5-110 mg L-1 PHB with a detection limit of 0.3 mg L-1 by the saturated
production of 3-HB; it can also take less than 15 min and result in a linear
detection range of 1.0-160 mg L-1 PHB with a detection limit of 0.5 mg L-1 by a
part production of 3-HB. The method also shows simple operation and high
reproducibility.
PMID- 17038771
TI - Triethylene glycol ether end-grafted carbosilane dendrimer: a potential ionophore
for potassium ion recognition.
AB - The performance of a newly synthesized carbosilane dendrimer bearing four
triethylene glycol ether (TEG) units, Si(CH2CH2CH2Si(Me)2CH2CH2CH2(OCH2CH2)3Me)4
(1), as ionophores in ion-selective electrodes has been investigated.
Optimization of the plasticized polyvinyl chloride membrane composition has
produced electrodes that exhibit a Nernstian response for potassium ions. The
best general characteristics exhibited by the electrodes were found when the
membrane composition ratio of DPE:1:NaTPB:PVC 60:3:2:35 (wt%) was used. The
response of the electrode was linear with a Nernstian slope of 58.3 mV/decade
over the K+ ion concentration range of 1.9x10(-7) to 1.0x10(-1) M with a
detection limit of 3.1x10(-7) M. The response time to achieve a 95% steady
potential for the K+ concentration ranging from 1.0x10(-1) to 1.0x10(-8) M was
less than 10 s, and it was found that the electrode is suitable for use within a
pH range of 5.5-8.5. The selectivity coefficients (log KPotK+,Mn+)), which were
determined by the fixed interference method, showed good selectivity for K+
against most of the interfering cations. The influence of this selective ion
binding behavior using electrospray ionization time-of-flight (ESI-TOF) mass
spectrometric studies is discussed.
PMID- 17038772
TI - A PVC plasticized sensor for Ni(II) ion based on a simple ethylenediamine
derivative.
AB - A new PVC membrane ion selective electrode which is highly selective towards
Ni(II) ions was constructed using a Schiff base containing a binaphthyl moiety as
the ionophore. The sensor exhibited a good Nernstian response for nickel ions
over the concentration range 1.0x10(-1)-5.0x10(-6) M with a lower limit of
detection of 1.3x10(-6) M. It has a fast response time and can be used for a
period of 4 months with a good reproducibility. The sensor is suitable for use in
aqueous solutions in a wide pH range of 3.6-7.4 and works satisfactorily in the
presence of 25% (v/v) methanol or ethanol. The sensor shows high selectivity to
nickel ions over a wide variety of cations. It has been successfully used as an
indicator electrode in the potentiometric titration of nickel ions against EDTA
and also for the direct determination of nickel content in real samples: effluent
samples, chocolates and hydrogenated oils.
PMID- 17038773
TI - A selective membrane electrode for lanthanum(III) ion based on a hexaaza
macrocycle derivative as ionophore.
AB - We have developed a highly La(III)-selective PVC membrane electrode based on a
hexaaza macrocycle, 8,16-dimethyl-6,14-diphenyl-2,3,4:10,11,12-dipyridine
1,3,5,9,11,13-hexaazacyclohexadeca-3,5,8,11,13,16-hexaene [Bzo2Me2Pyo2(16)
hexaeneN6] (I) as membrane carrier, dibutylbutyl phosphonate (DBBP) as solvent
mediator and sodium tetraphenylborate (NaTPB) as lipophilic additive. The best
performance was given by the membrane of macrocycle I having a composition
10:260:5:120 (I:DBBP:NaTPB:PVC). The electrode exhibits a Nernstian response to
La(III) ion in the concentration range 1.0x10(-1)-7.94x10(-7) M with a slope of
19.8+/-0.2 mV/decade of concentration and a detection limit of 5.62x10(-7) M. The
response time of the sensor is 12 s and it can be used over a period of 4 months
with good reproducibility. The electrode works well over a pH range of 2.5-10.0
and in partially non-aqueous medium with up to 30% organic content. The sensor
was also used as an indicator electrode in potentiometric titration of La(III)
ions with EDTA and for determining La(III) concentration in real samples.
PMID- 17038774
TI - Highly selective iodide electrode based on the copper(II)-N,N'-bis(salicylidene)
1,2-bis(p-aminophenoxy)ethane tetradentate complex.
AB - In this paper, a new PVC-based liquid-membrane anion-selective electrode based on
a copper(II) of N,N'-bis(salicylidene)-1,2-bis(p-aminophenoxy)ethane tetradentate
complex (Cu(II)BBAP) is described, which displays a preferential potentiometric
response to iodide ion at pH 2.0 and an anti-Hofmeister selectivity sequence: I
>SCN->ClO4->NO2->H2PO4->NO3->SO4(2-)>Br->Cl-. The electrode exhibits a near
Nernstian potential linear range of 8.2x10(-7)-1.0x10(-1) M with a detection
limit of 5.3x10(-7) M and a slope of -58.8 mV per decade. The A.C. impedance
technique and the UV/Vis spectroscopy technique were used to analyze the response
mechanism. The electrode could be applied to determine iodide in medicine
analysis, and the obtained results were fairly satisfactory.
PMID- 17038775
TI - Determination of trace levels of diosmin in a pharmaceutical preparation by
adsorptive stripping voltammetry at a glassy carbon electrode.
AB - A systematic study on the electrochemical behavior of diosmin in Britton-Robinson
buffer (pH 2.0-10.0) at a glassy carbon electrode (GCE) was made. The oxidation
process of the drug was found to be quasi-reversible with an adsorption
controlled step. The adsorption stripping response was evaluated with respect to
various experimental conditions, such as the pH of the supporting electrolyte,
the accumulation potential and the accumulation time. The observed anodic peak
current at +0.73 V vs. Ag/AgCl reference electrode increased linearly over two
orders of magnitude from 5.0x10(-8) M to 9.0x10(-6) M. A limit of detection down
to 3.5x10(-8) M of diosmin at the GCE was achieved with a mean recovery of 97+/
2.1%. Based on the electrochemical data, an open-circuit accumulation step in a
stirred sample solution of BR at pH 3.0 was developed. The proposed method was
successfully applied to the determination of the drug in pharmaceutical
formulations. The results compared favorably with the data obtained via
spectrophotometric and HPLC methods.
PMID- 17038776
TI - Preparation and evaluation of uniform-size (-)-ephedrine-imprinted polymeric
microspheres by multi-step swelling and suspension polymerization.
AB - Ephedrine-imprinted polymeric microspheres have been prepared in an aqueous
system by multi-step swelling and suspension polymerization, using methacrylic
acid (MAA) as a functional monomer, and ethylene glycol dimethacrylate (EGDMA) as
a cross-linker. Scanning electron microscopy (SEM) was used as a means to
identify the structure features of the obtained polymers. Further, we examined
the recognition mechanism of the polymers and the influences of some
chromatographic conditions, such as the mobile-phase composition, flow-rate,
column temperature and sample amount on the retentivity and selectivity for (-)
ephedrine and (+)-ephedrine. The results reveal that stable macroporous polymer
beads with good size monodispersity were obtained, the average size of which was
3-5 microm. Baseline chiral separation of the template isomers was achieved on a
short column (50 mmx4.6 mm i.d.) when the prepared polymer beads were used as a
stationary phase, while the non-imprinted polymers (NIPs) did not show such
ability. The optimized chromatographic condition was as follows: acetonitrile
acetic acid (99.8/0.2, v/v) as the mobile phase; sample amount, 40-80 microg;
flow rate, 1.0 ml min-1; and column temperature, room temperature, respectively.
It is assumed that two classes of binding sites exist in the porous polymers, one
being hydrophilic binding sites, the other being hydrophobic binding sites.
PMID- 17038777
TI - UV irradiation controlled cold vapor generation using SnCl2 as reductant for
mercury speciation.
AB - A simple and ultrasensitive method, which was based on cold vapor generation
(CVG) coupled to atomic fluorescence spectrometry (AFS), was proposed for
speciation analysis of inorganic mercury (Hg2+) and methylmercury (MeHg) in water
samples. In the presence of UV irradiation, all the mercury (MeHg+Hg2+) in a
sample solution can be reduced to Hg0 by SnCl2; without UV irradiation, only Hg2+
species can be determined. So the concentration of MeHg can be obtained from the
difference of the total mercury and Hg2+ concentration; thus, speciation analysis
of Hg2+ and MeHg was simply achieved without chromatographic separation. Under
the optimized experimental conditions, the limits of detection were 0.01 ng mL-1
for both Hg2+ and MeHg. The sensitivity and limit of detection were not dependent
on the mercury species, and a simple Hg2+ aqueous standard series can be used for
the determination of both Hg2+ and MeHg.
PMID- 17038779
TI - Determination of trace impurities in high-purity cadmium by high-resolution
inductively coupled plasma mass spectrometry.
AB - Trace impurities in high-purity cadmium were determined by high-resolution
inductively coupled plasma mass spectrometry (HR-ICP-MS). To overcome some
potentially problematic spectral interference, measurements were acquired in both
medium and high-resolution modes. The matrix effects due to the presence of
excess HCl and cadmium were evaluated. The optimum conditions for the
determination were tested in this experiment and discussed. The detection limits
ranged from 0.01 to 0.27 microg g-1, depending on the elements. The results for
the determination of 22 trace elements in high-purity cadmium are presented.
PMID- 17038778
TI - Ultra-sensitive colorimetric method to quantitate hundreds of polynucleotide
molecules by gold nanoparticles with silver enhancement.
AB - An ultra-sensitive colorimetric method to quantitate hundreds of polynucleotide
molecules by gold nanoparticles with silver enhancement has been developed. The
hybridization products from the target polynucleotides with biotin-labeled probes
and gold nanoparticle-functioned oligonucleotides were immobilized to microplates
via avidin-biotin system, and the absorbance signals of gold nanoparticles were
amplified by silver enhance solution. This sandwich colorimetric assay can detect
as few as 600 molecules for single-strand oligonucleotides and as few as 6000
molecules for double-strand polynucleotides in a 50 microL reaction system.
PMID- 17038780
TI - Multiple-element detection in aqueous solution and seawater by using an on-line
preconcentration method for inductively coupled plasma mass spectrometry.
AB - Inductively coupled plasma-mass spectrometry (ICP-MS) incorporated with an on
line preconcentration system was used to determine trace amounts of ten metals
including Ni, Cu, Zn, Rh, Ag, Cd, In, Au, Tl, and Pb in aqueous solutions and
seawater. These metals, which formed the complexes, were retained in a sorbent
microcolumn, followed by elution with methanol through a desolvation unit, which
was capable of removing 83% of methanol. The limits of detection for these
elements were determined simultaneously to be in the range from 3 to 20 ng/L.
PMID- 17038782
TI - [Glucose-induced insulin secretion independent of ATP-sensitive K+ channels].
PMID- 17038783
TI - [H2S production by L-cysteine metabolism inhibits insulin release].
PMID- 17038784
TI - [SOX6 attenuates glucose-stimulated insulin secretion by repressing PDX1
transcriptional activity].
PMID- 17038785
TI - [PPAR delta and metabolic syndrome].
PMID- 17038786
TI - [Decreased PPARs activity mediated induction of anoikis and inability of cell
adhesion and invasion in colorectal carcinoma cells].
PMID- 17038787
TI - [PPAR gamma ligand pioglitazone as a therapeutic strategy in nonalcoholic
steatohepatitis (NASH)].
PMID- 17038788
TI - [Preparation of parotid acinar cells].
PMID- 17038789
TI - [Observation and recording of mouse jaw movements with a novel restrictor system
and a behavioral check list].
PMID- 17038790
TI - [Basis of anti-glaucoma agents].
PMID- 17038791
TI - [Clinical application of glaucoma medications].
PMID- 17038792
TI - [Pharmacological and clinical profile of silodosin (URIEF Cap. 2 mg, 4 mg)].
PMID- 17038793
TI - Sex chromosome-linked genes in plants.
AB - Recent studies of plant sex chromosome-linked genes have revealed many
interesting characteristics, although there are limited reports about
heteromorphic sex chromosomes in flowering plants. Sex chromosome-linked genes in
angiosperms have been characterized mainly in the dioecious plant Silene
latifolia. Although all such genes were isolated from transcripts of male flower
buds of S. latifolia, most seem to be housekeeping genes except for the petal-
and stamen-specific MADS box gene on the Y chromosome (SlAP3Y) and the male
reproductive organ-specific gene on the X chromosome (MROS3X). Recent
evolutionary studies have revealed at least three evolutionary strata on the X
chromosome that are related to stepwise loss of recombination between the sex
chromosomes. Moreover, genetic maps showed conservation of gene organization on
the X chromosome in the genus Silene and substantial pericentric inversion
between the X and Y chromosomes of S. latifolia during evolution. A comparison
between paralogs on the sex chromosomes revealed that introns of the Y-linked
genes are longer than those of X-linked paralogs. Although analyses of sex
chromosome-linked genes suggest that degeneration of the Y chromosome has
occurred, the Y chromosome in flowering plants remains the largest in the male
genome, unlike that of mammals. Accumulation of repetitive sequences and the
entire chloroplast genome on the Y chromosome appear to have contributed to this
large size. However, more detailed studies will be required to help explain the
basis for the fact that heteromorphic sex chromosomes in angiosperms are large.
PMID- 17038795
TI - Characterization of DNA methyltransferase genes in Brassica rapa.
AB - DNA methylation is essential for normal development and plays important roles in
regulating gene expression in plants. Analysis of the key enzymes catalyzing DNA
methylation is important to understand epigenetic phenomena. In this study, three
putative methyltransferase genes, BrMET1a, BrMET1b, and BrCMT, were isolated from
a genome library of Brassica rapa. Structural conservation of the amino acid
sequence between BrMET1a/BrMET1b and AtMET1 and that between BrCMT and AtCMT3
suggests that they may function as DNA methyltransferase. BrMET1a was expressed
in vegetative and reproductive organs, while BrMET1b was expressed only in
pistils, indicating that these two genes have different functions. BrCMT was
expressed especially in stamens at the stage of 2-4 days before anthesis. We
isolated three DNA methyltransferase genes in Brassica rapa and indicated
differences of expression patterns of these DNA methyltransferase genes and
expression levels in different tissues and developmental stages, suggesting that
these genes might play important roles in epigenetic gene regulation in B. rapa.
PMID- 17038794
TI - Expression of germination-related enzymes, CspA, CspB, CspC, SleC, and SleM, of
Clostridium perfringens S40 in the mother cell compartment of sporulating cells.
AB - In Clostridium perfringens S40, spore germination-specific enzymes are
synthesized during sporulation. Previous reports have demonstrated that two
cortex-lytic enzymes, SleC and SleM, and a component of germination-specific
protease, CspC, are located outside the cortex as an integral part of the dormant
spore. In the present study, we examined the time and compartment of these
enzymes' gene expression using reverse transcription-PCR (RT-PCR) and
fluorescence microscopy on green fluorescence protein (GFP)-fused proteins. These
results suggested that CspABC, SleC, and SleM are synthesized in the mother cell
compartment of sporulating cells, probably at stages II approximately III of
sporulation, and that the expression of cspABC genes is tricistronic.
PMID- 17038796
TI - Genetic variations in the chloroplast genome and phylogenetic clustering of
Lycoris species.
AB - The genus Lycoris of Amaryllidaceae comprises approximately 20 species that are
distributed only in the moist warm temperate woodlands of eastern Asia. The
objectives of this study were: (1) to clarify the phylogeny of the Lycoris
species by using the definitive DNA sequencing method and (2) to examine the
possible maternal donor of the hybrid origin Lycoris species and the Japanese
triploid strains of Lycoris radiata var. radiata. The nucleotide sequence of the
maturase K (matK) gene and the noncoding intergenic spacer (IGS) between the atpB
and rbcL genes in the chloroplast genome were determined in a total of 27 strains
of 11 species of the genus Lycoris. Variation among taxa was mainly due to
nucleotide substitution, although deletions and an insertion were found in the
IGS. For two chloroplast regions, the phylogenetic trees showed essentially
similar topology, indicating the existence of four clades, I, II, III, and IV.
For all the species except L. radiata, intraspecific variation was smaller than
interspecific variation. For L. radiata, triploid strains were divided into
clades I and II, and diploid strains were divided into clades I and IV. This
implies that the diploid species of L. radiata var. pumila is a probable
ancestral species. The clustering indicated that the chloroplast genome has not
evolved in parallel with the karyotype in genus Lycoris. Regarding the hybrid
origin species, the maternal parents of L. squamigara, L. albiflora and L. rosea
were revealed to be L. longituba, L. radiata and L. radiata var pumila,
respectively. We also suggest that a diploid strain of L. radiata var. pumila in
clade I might be a candidate of the maternal donor of the Japanese triploid
strains. A possible model of the maternal donor of Lycoris species is proposed.
PMID- 17038797
TI - Complete assignment of structural genes involved in flavonoid biosynthesis
influencing bulb color to individual chromosomes of the shallot (Allium cepa L.).
AB - We analyzed Japanese bunching onion (Allium fistulosum L.) - shallot (Allium cepa
L. Aggregatum group) alien chromosome addition lines in order to assign the genes
involved in the flavonoid biosynthesis pathway to chromosomes of the shallot. Two
complete sets of alien monosomic additions (2n = 2x + 1 = 17) were used for
determining the chromosomal locations of several partial sequences of candidate
genes, CHS, CHI, F3H, DFR, and ANS via analyses of PCR-based markers. The results
of DNA marker analyses showed that the CHS-A, CHS-B, CHI, F3H, DFR, and ANS genes
should be assigned to chromosomes 2A, 4A, 3A, 3A, 7A, and 4A, respectively. HPLC
analyses of 14 A. fistulosum - shallot multiple alien additions (2n = 2x + 2 - 2x
+ 7 = 18 - 23) were conducted to identify the anthocyanin compounds produced in
the scaly leaves. A direct comparison between the genomic constitution and the
anthocyanin compositions of the multiple additions revealed that a 3GT gene for
glucosylation of anthocyanidin was located on 4A. Thus, we were able to assign
all structural genes involved in flavonoid biosynthesis influencing bulb color to
individual chromosomes of A. cepa.
PMID- 17038798
TI - Molecular cloning and characterization of the mouse Na+ sulfate cotransporter
gene (Slc13a4): Structure and expression.
AB - Sulfate is an essential ion required for numerous functions in mammalian
physiology. Due to its hydrophilic nature, cells require sulfate transporters on
their plasma membranes to allow entry of sulfate into cells. In this study, we
identified a new mouse Na(+)-sulfate cotransporter (mNaS2), characterized its
tissue distribution and determined its cDNA and gene (Slc13a4) structures. mNaS2
mRNA was expressed in placenta, brain, lung, eye, heart, testis, thymus and
liver. The mouse NaS2 cDNA spans 3384 nucleotides and its open frame encodes a
protein of 624 amino acids. Slc13a4 maps to mouse chromosome 6B1 and contains 16
exons, spanning over 40 kb in length. Its 5'-flanking region contains CAAT- and
GC-box motifs and a number of putative transcription factor binding sites,
including GATA-1, MTF-1, STAT6 and HNF4 consensus sequences. This is the first
study to define the tissue distribution of mNaS2 and resolve its cDNA and gene
structures, which will allow us to investigate mNaS2 gene expression in vivo and
determine its role in mammalian physiology.
PMID- 17038799
TI - Seasonal fluctuation in susceptibility to insecticides within natural populations
of Drosophila melanogaster. II. Features of genetic variation in susceptibility
to organophosphate insecticides within natural populations of D. melanogaster.
AB - To elucidate genetic variation in susceptibility to organophosphate insecticides
within natural populations of Drosophila melanogaster, we conducted an analysis
of variance for mortality data sets of isofemale lines (10-286 lines) used in the
previous studies. Susceptibility of isofemale lines to the three organophosphate
insecticides was continuously distributed within each natural population, ranging
from susceptible to resistant. Analysis of variance showed highly significant
variation among isofemale lines in susceptibility to each insecticide for each
natural population. Significant genetic variances in susceptibility to the three
chemicals were estimated for the Katsunuma population; 0.0529-0.2722 for
malathion, 0.0492-0.1603 for prothiophos, and 0.0469-0.1696 for fenitrothion.
Contrary to the consistent seasonal tendency towards an increase in mean
susceptibility in the fall, reported in the previous study, genetic variances in
susceptibility to the three organophosphates did not change significantly in 1997
but tended to increase by 2- to 5-times in 1998. We tested whether both the
observed situations, maintenance and increase in genetic variance in
organophosphate resistance, can be generated under circumstances in which the
levels of resistance to the three organophosphates tended to decrease, by
conducting a simulation analysis, based on the hypothesis that resistant
genotypes have lower fitnesses than susceptible ones under the density
independent condition. The simulation analysis generally explained the pattern in
the mean susceptibility and genetic variances in susceptibility to the three
organophosphates, observed in the Katsunuma population of D. melanogaster. It was
suggested that the differences in the frequencies of resistance genes in the
summer population could affect the patterns in genetic variance in
organophosphate resistance in the fall population.
PMID- 17038800
TI - Chromosome-specific satellite sequences in Turritis glabra.
AB - Two novel repetitive sequence families were isolated from Turritis glabra (2n =
2x = 12). These two repeat families are similar to those of centromeric repeats
in Arabidopsis thaliana, are co-localized on one chromosome pair, and differ by
about 20% from each other. Phylogenetic analysis revealed that the two repeat
families of T. glabra are more similar to each other than to the centromeric
repeat families of other Arabidopsis and related species. The relationships of
satellite sequences reflected the species phylogeny, indicating that the
replacement of satellite sequences has occurred in each species lineage
independently, and shared variants could not have existed for a long time between
species.
PMID- 17038801
TI - The role of UvrD in RecET-mediated illegitimate recombination in Escherichia
coli.
AB - To study the mechanism of RecET-mediated illegitimate recombination, we examined
the formation of lambdabio-transducing phage in Escherichia coli in the presence
or absence of UV irradiation. We have previously reported that coexpression of
RecE and RecT enhances the frequency of recA-independent illegitimate
recombination. RecJOR proteins are required for this RecET-mediated illegitimate
recombination, and RecQ suppresses it. Here, we showed that the frequencies of
both spontaneous and UV-induced RecET-mediated illegitimate recombination events
are reduced by a uvrD mutation. It should be noted that UvrD is required for
illegitimate recombination only in the presence, but not in the absence, of
RecET. In contrast, frequencies of RecET-mediated illegitimate recombination were
not affected by ruvAB, ruvC, recG, and recN mutations. The frequency of
spontaneous and UV-induced illegitimate recombination in the uvrD recR double
mutant was comparable to that of the uvrD single mutant, suggesting that UvrD
works at the same step as RecR in the RecET-mediated recombination pathway.
Nucleotide sequence analyses of the recombination junctions showed that RecET
mediated illegitimate recombination detected in UvrD-deficient strain is short
homology-dependent. Based on these and previous results, we propose a model for
the role of UvrD on RecET-mediated illegitimate recombination.
PMID- 17038802
TI - Beneficial action of 2,4,4-trimethyl-3-(15-hydroxypentadecyl)-2-cyclohexen-1-one,
a novel long-chain fatty alcohol, on diabetic hypoalgesia and neuropathic
hyperalgesia.
AB - The effects of 2,4,4-trimethyl-3-(15-hydroxypentadecyl)-2-cyclohexen-1-one
(tCFA15) on diabetic hypoalgesia and neuropathic hyperalgesia were examined.
Treatments of streptozotocin (STZ)-pretreated mice with tCFA15 (8 - 40 mg/kg,
i.p.) for 7 days significantly reversed the depressed inflammatory nociceptive
licking response in the formalin test. In addition, similar drug treatments and
dosing in 7-day postoperative neuropathic pain model rats (prepared by the method
of Bennett and Xie) yielded a similarly favorable outcome by significantly
reversing decreased nociceptive thresholds in the paw pressure test. These
results suggest that tCFA15 may have the potential to normalize sensory nerve
abnormalities induced in experimental diabetes and nerve injury.
PMID- 17038803
TI - Distribution of DJ-1, Parkinson's disease-related protein PARK7, and its
alteration in 6-hydroxydopamine-treated hemiparkinsonian rat brain.
AB - DJ-1 has multiple functions and its dysfunction may be linked to the onset of
familial Parkinson's disease PARK7. However, the function and distribution of DJ
1 is unclear. In this study, we determined DJ-1 distribution and change after
intranigral injection of 6-hydroxydopamine (6-OHDA). Although distribution of DJ
1 immunoreactivity was not changed in cerebral cortex and striatum, 6-OHDA caused
increase of DJ-1 in the particulate fraction and decrease in the cytosolic
fraction in substantia nigra. At that time, DJ-1 shifted to acid forms. These
results suggest that distributional changes, translocation, and acidic shift of
DJ-1 may be compensatory responses to protect against 6-OHDA-induced oxidative
stress.
PMID- 17038804
TI - Effect of gestational exposure to nonylphenol on the development and fertility of
mouse offspring.
AB - Nonylphenol (NP), a kind of environmental chemical, is thought to imitate
endogenous hormones, inhibit the actions of hormones, and induce reproductive
abnormalities. A number of experimental animals, usually rats, have been used to
evaluate the potential reproductive toxicity of NP. However, the findings of
previous studies were contradictory in some cases. Therefore, we used ICR mice as
a biomodel for in utero study of NP. After mating, 8- to 12-week-old females were
assigned to four groups (n=8) for subcutaneous injections from day 5 to 20 of
gestation. Group I animals received corn oil alone as a control, while the mice
of groups II, III and IV received NP at concentrations of 1/1000, 1/100 and 1/10
of the LD(50), respectively. A dose-dependent decrease was observed in terminal
body weights of males of the F1 generation; however, a very small negative effect
was only found in the females of the NP1/10 group. No significant effect was
found on the liver weights of both sexes. The weights of the testis and
epididymis were slightly decreased in the NP1/10 group. The NP1/100 treatment
increased ovary weight considerably. The uterus weight tended to be increased in
the NP treatment groups; however, there were large variations. The gestational
exposure of the groups had no significant effect on the rate of pregnancy (94.4
100%) and the number of fetuses per litter (13.6-14.3 males, 12.3-13.7 females)
compared with the control group. However, the overall mortality of
fetuses/embryos was increased considerably in the NP1/100 (male: 13.9%) and
NP1/10 (female: 9.8%) groups. These results suggest that exposure to NP in utero
possibly affects the body weight and some reproductive organ weights, but does
not influence the potential fertility of the F1 generation.
PMID- 17038805
TI - Nuclear accumulation and activation of nuclear factor kappaB after split-dose
irradiation in LS174T cells.
AB - Although radiation-induced gene expression has been extensively studied, most of
the studies to date have focused on that after single-dose irradiation. As split
dose irradiation, rather than single-dose irradiation, is usual in clinical
situations, we investigated the effects of split-dose irradiation on nuclear
factor kappaB (NF-kappaB) in the human rectum carcinoma cell line, LS174T. After
either single- or split-dose irradiation with a different interval, nuclear
localization of NF-kappaB was examined by Western blot and immunofluorescence and
its DNA-binding activity was measured by ELISA-based assay. Irradiation-induced
NF-kappaB nuclear accumulation and DNA binding activity increased in a dose
dependent manner. The peak of NF-kappaB nuclear accumulation and DNA binding
activity was seen 2 to 6 hours after a single dose of 4 Gy irradiation and
returned to control levels after 12 hours. In split-dose irradiation, NF-kappaB
activity was similar after the first and second doses of 4 Gy irradiation
separated by 12 hours. In addition, NF-kappaB activity was decreased by
lengthening the interval between irradiation. The cell survival, which was
assessed by colony formation assay, showed inverse correlation to this: the
surviving fraction was higher after split-dose irradiation than after single-dose
irradiation of the same total dose and it increased as the interval between
irradiation was lengthened. Thus the present results showed a correlation between
NF-kappaB activation and the repair of sublethal damage in split-dose
irradiation.
PMID- 17038806
TI - [Innate immune recognition of viral infection].
AB - Toll-like receptors (TLRs) are key molecules of the innate immune systems, which
detect conserved structures found in a broad range of pathogens and triggers
innate immune responses. A subset of TLRs recognize viral components and induce
antiviral responses by producing type I interferons. Whereas TLR2 and TLR4
recognize viral components at the cell surface, TLR3, TLR7, TLR8 and TLR9 are
exclusively expressed in endosomal compartments. After phagocytes internalize
viruses or virus-infected apoptotic cells, viral nucleic acids are released in
phagolysosomes and are recognized by these TLRs. Recent reports have shown that
hosts also have a mechanism to detect replicating viruses in the cytoplasm in a
TLR-independent manner. In this review, we focus on the viral recognition by
innate immunity and the signaling pathways.
PMID- 17038807
TI - [Study of animal viruses in yeast].
AB - Yeast is often considered to be a model eukaryotic organism, in a manner
analogous to E. coli as a model prokaryotic organism. Yeast has been extensively
characterized and the genomes completely sequenced. Despite the small genome
size, yeast displays most of features of higher eukaryotes. The facts that most
of cellular machinery is conserved among different eukaryotes and that the
powerful technologies of genetics and molecular biology are available have made
yeast model eukaryotic cells in biological and biomedical sciences including
virology. Cumulative data indicate that yeast can be a host for animal viruses. I
briefly describe yeast gene expression and review viral replication in yeast.
Great discovery include complete replication of animal viruses and production of
virus-like particle vaccines in yeast. Current studies on yeast focus on
identification of host factors and machinery used for viral replication. The
studies are based on traditional yeast genetics and genome-wide identification
using a complete set of yeast deletion strains.
PMID- 17038808
TI - [Development of intranuclear inclusions of human polyomavirus JC. Capsid proteins
are assembled into virions at the PML nuclear bodies].
AB - Human polyomavirus JC (JCV) is a causative agent for progressive multifocal
leukoencephalopathy, a fatal demyelinating disorder. The viruses form
intranuclear viral inclusions in infected oligodendrocytes. The outer capsid of
JCV is thought to be composed of 360 molecules of major capsid protein VP1, and
minor capsid proteins VP2 and VP3 in an appropriate ratio. However, the
regulatory mechanisms of gene expression for the capsid proteins, their nuclear
transport, and formation of viral inclusions are not well understood. We have
recently clarified the following regarding the mechanism underlying JCV virion
assembly; (i) major and minor capsid proteins are synthesized from messenger
RNAs, the expression ratio of which is determined by alternative splicing, (ii)
messenger RNAs for the major and minor capsid proteins are polycistronic, and
their translation occurs downstream of the regulatory protein, agnoprotein, (iii)
major and minor capsid proteins are translocated to the nucleus in a cooperative
manner and accumulate at the dot-shaped intranuclear structures called
promyelocytic leukemia nuclear bodies (PML-NBs), (iv) efficient viral replication
can occur at the PML-NBs, where capsid assembly is likely to be associated with
viral DNA replication. PML-NBs are the sites for expression of important nuclear
functions for the host cells. The finding that the target of JCV infection is the
PML-NB may contribute greatly to our understanding of the mechanism underlying
cellular degeneration, which occurs after the formation of intranuclear viral
inclusions.
PMID- 17038809
TI - [Cellular tropism and adaptation of the measles virus].
AB - Measles virus (MV) is a member of the genus Morbillivirus in the family
Paramyxoviridae. Clinical isolates of MV use signaling lymphocyte activating
molecule (SLAM) as a cellular receptor. SLAM is mainly expressed on immune cells
such as immature thymocytes, activated lymphocytes and mature dendritic cells.
This distribution of SLAM can account for the lymphotropism of MV. On the other
hand, laboratory strains of MV use CD46 as an alternative receptor, through amino
acid change(s) in the receptor binding hemagglutinin protein. Recently, several
reports imply the existence of the cellular receptor(s) other than SLAM and CD46.
In this review, we discuss the receptor usage of MV and its adaptation to
cultured cells.
PMID- 17038810
TI - [Analysis of the mechanisms of tobamovirus RNA replication].
AB - The replication of eukaryotic positive-strand RNA virus genomes occurs in
membrane-bound replication complexes. Currently, little is known about the
process of replication complex formation and the molecular structure of the
replication complexes. We are trying to understand how eukaryotic positive-strand
RNA viruses replicate using tobamoviruses as models. Here, I describe our
approaches to this end.
PMID- 17038811
TI - [Host factors that regulate the intercellular dynamics of HIV-1 genome during the
early phase of infection].
AB - An interplay or battle between virus and its host has been observed within a
single cell. Upon an infection with retroviruses including human immunodeficiency
virus type 1 (HIV-1), the viral genome is subjected to several processes that
include uncoating, reverse transcription of the viral genomic RNA into a cDNA
copy, transport of this cDNA into the nucleus, and integration of the cDNA into
the host chromosome. Antiretroviral restriction factors such as TRIM5 alpha and
APOBEC3G have been recently identified. In addition, nuclear membrane protect
host chromosomal DNA against incoming viral genome. For successful retroviral
infection, viral genome must overcome these cellular barriers to establish
proviral state, in which viral cDNA was stably integrated into host chromosomal
DNA. In this review, I would summarize the host factors that regulate the
intercellular dynamics of HIV-1 genome during the early phase of infection,
especially focusing on factors interacting with HIV-1 integrase and the
preintegration complex.
PMID- 17038812
TI - [Dissemination pathways for poliovirus cells to animals models].
AB - It is considered there are two main pathways for poliovirus dissemination towards
the central nervous system in humans. One is the pathway through the blood brain
barrier. The orally ingested virus invades into the blood circulation, and then
the virus permeates into the central nervous system through the blood brain
barrier. The other is the neural pathway. In this pathway, the intramuscularly
inoculated virus is transported through the axons from the synapse to the cell
body in the central nervous system. We have developed the oral infection system
using the mouse models. Moreover, we proposed the possibility that PV is
transcytosed through the brain capillary epithelia in a specific manner. As for
the neural pathway, we have proved that PV is endocytosed into CD155 containing
vesicles and the vesicles are retrogradely transported in the axon of rat primary
motor neuron. We have also shown that the cytoplasmic dynein takes part in the
transport.
PMID- 17038813
TI - [Poliovirus susceptibility in cultured cells--an answer to Enders].
AB - Poliovirus is the causative agent of poliomyelitis. It replicates efficiently in
the neurons in the central nervous system and produces severe pathological
lesions. It cannot replicate well in the non-neural tissues. In spite of this
strict neurotropism in vivo, however, it can replicate in cells of monolayer
cultures derived from almost any tissues of primates as Enders and colleagues
initially shown. It was supposed that cellular changes during the process of
cultivation were required for acquisition of susceptibility. This question
remained unsolved for a long time. We have recently shown that cells in culture
acquire poliovirus susceptibility by loosing rapid and robust interferon response
that has been normally maintained in tissues in vivo.
PMID- 17038814
TI - [Seasonal influenza activity in Japan and epidemiological investigation for avian
influenza].
AB - We analyzed the seasonal influenza activity in 2004/05 and 2005/06 seasons. In
2004/05 season, the prevalence of influenza started lately. The arrival of a peak
of influenzal prevalence was the ninth week, and was late in comparison with an
average year. The prevalence scale was very large, and the estimation number of
patients was 17,700,000. Since the start of the 2004/05 season, influenza
activity has mainly been associated with influenza B viruses. The start of
prevalence of 2005/06 season was 50th week and was comparatively early. The peak
of the prevalence was the 4th week, same as an average year. Since the start of
the 2005/06 season, influenza activity has mainly been associated with influenza
A/H3 viruses.H5N1 highly pathogenic avian influenza virus have spread through
Africa and Europe from Asia. For purpose such as inhibition of the outbreak of
new variant influenza, the prevention of human to human infection and expansion,
early containment, the public health organization has to do unified
epidemiological investigation immediately nationwide. By doing epidemiological
investigation, the prevention of infection expansion, specification of the source
of infection, assessment of the risk of infection, and early detection of new
variant influenza virus and containment, are expected.
PMID- 17038815
TI - [Preparedness and international contribution on H5N1 highly pathogenic avian
influenza and pandemic-influenza].
AB - Since the end of 2003, simultaneous outbreaks caused by H5N1 highly pathogenic
avian influenza viruses (H5N1-HPAIV) occurred in poultries and in wild birds in
the East Asia. The outbreaks are spreading now at least 48 countries in the
Middle Eastern, African and European countries in addition to the East Asia.
During the outbreaks, over 200 human infection cases with 55% fatality are
confirmed at the moment and some human-to-human transmission in family clusters
have been observed. The outbreaks are no more out of control and pandemic
potential caused by H5N1-HPAIV is major concern. Therefore, it is urgently
necessary to develop new diagnostic kits and effective vaccines and to stockpile
anti-influenza drugs before pandemic alert period phase 4 defined by WHO.
Furthermore, international supports to the affected countries for development and
improvement of diagnostic system are required in the public health aspect.
PMID- 17038816
TI - [Influenza virus receptors in the human airway].
AB - Avian influenza A (H5N1) virus infections have resulted in more than 100 human
deaths; yet, human-to-human transmission is rare. We demonstrated that the
epithelial cells in the upper respiratory tract of humans mainly possess sialic
acid linked to galactose by alpha 2,6 linkages (SA alpha 2,6Gal), a molecule
preferentially recognized by human viruses. However, many cells in the
respiratory bronchioles and alveoli possess SA alpha 2,3Gal, which is
preferentially recognized by avian viruses. These facts are consistent with the
observation that H5N1 viruses can be directly transmitted from birds to humans
and cause serious lower respiratory tract damage in humans. Furthermore, this
anatomical difference in receptor prevalence may explain why the spread of H5N1
viruses among humans is limited. However, since some H5N1 viruses isolated from
humans recognize human virus receptors, additional changes must be required for
these viruses to acquire the ability for efficient human-to-human transmission.
PMID- 17038817
TI - [Accumulation of amino acid substitutions promotes irreversible structural
changes in the hemagglutinin of human influenza AH3 virus during evolution].
AB - During protein evolution the amino acid substitutions accumulate with time.
However, the effect of accumulation of the amino acid substitutions to structural
changes has not been estimated well. We will propose that the discordance of
amino acid substitution on the HA protein of influenza A virus is useful for the
assessment of structural changes during evolution. Discordance value can be
obtained from the experimental data of tolerance or intolerance by introducing
site directed mutagenesis at the homologous positions of two HA proteins holding
the same amino acid residues. The value of discordance correlated to the number
of amino acid differences among proteins. In the H3HA discordance rate was
calculated to be 0.45% per one amino acid change. Furthermore, discordance of
amino acid substitutions suggests that tolerable amino acid substitutions in
different order have a probability of promoting irreversible divergence of the HA
protein to different subtypes.
PMID- 17038818
TI - [Molecular mechanism of replication and transcription of the influenza virus
genome and host factors].
AB - The genome of influenza A virus is a set of eight segmented- and single-stranded
RNAs. A basic transcription and replication unit is the genome complexed with
viral RNA-dependent RNA polymerases and nucleoprotein (NP). For the efficient
transcription and replication of the genome, not only viral factors but also host
cell-derived factors are required. Although receptor and protease molecules play
important roles in infection and pathogenicity, it is also possible that host
factors involved in the virus genome function determine these. PB2, for instance,
is reported to be a possible candidate for determination of the host range of
avian influenza viruses. Here we summarize recent progresses in the molecular
mechanism of the influenza virus genome transcription and replication and discuss
the involvement of host factors in these processes.
PMID- 17038819
TI - [Diagnosis and Treatment of influenza--clinical investigation on viral shedding
in children with influenza].
AB - Children with influenza usually shed viruses from the several days before onset
of clinical symptoms, and viruses are isolated for one or two weeks after onset.
Point-of-care rapid diagnostic tests are useful to guide use of antiviral agents,
appears over 90% sensitivity and specificity for influenza A with nasopharyngeal
specimens compared with cell culture. The detection limits of these test kits are
103 pfu or over, so it is necessary to consider viral load in clinical specimens
for diagnosis with these kits. Viral load are decreased after the start of
antiviral agents, but influenza viruses are isolated in more than half of
pediatric patients when fever get down, and resistant viruses are detected in
some of these patients. It is very important for influenza control to investigate
on viral shedding and resistant viruses.
PMID- 17038820
TI - [Properties of the Ebola virus glycoprotein].
AB - In central and west Africa, Ebola virus, a member of the filovirus group, has
produced sporadic outbreaks of lethal disease. This virus causes hemorrhagic
fever in humans and nonhuman primates, resulting in mortality rates of up to 90%.
Although there are no satisfactory biologic explanations for this extreme
virulence, it has been suggested that functions of the envelope glycoprotein are
likely to play important roles in the pathogenicity of Ebola virus.
PMID- 17038821
TI - Delivering pneumococcal vaccine to a high risk population: the Navajo experience.
AB - High rates of preventable diseases such as pneumococcal disease occur among the
Navajo despite their universal health insurance through the Indian Health
Service. The objective of this study was to determine the proportion of Navajo
adults vaccinated with pneumococcal polysaccharide vaccine and to examine key
features of vaccination programs of the Navajo Indian Health Service. For this
cross-sectional study, medical charts of Navajo patients with vaccine indications
were randomly selected and reviewed to determine who had been vaccinated as of
January 1, 1999. Among 480 Navajo>or=65 years old, 73% were vaccinated (95%
confidence interval [CI]: 69%-77%). Among 111 Navajo 18-64 years old with vaccine
indications, 54% were vaccinated (95% CI: 45% -63%). Vaccination programs
utilized extensive public health nursing, home visits, standing orders, and
"express lane" clinics. In spite of excellent delivery systems and universal
healthcare, the proportion of Navajo persons vaccinated was still below the goals
for Healthy People 2010 of having 90% of persons>or=65 years old vaccinated and
60% of high-risk persons 18-64 years old vaccinated.
PMID- 17038822
TI - Physician knowledge and perspectives regarding influenza and influenza
vaccination.
AB - BACKGROUND: Recent studies have demonstrated that healthy children younger than
24 months of age are at risk for influenza-associated hospitalization and
influenza related complications. In light of this, the American Academy of
Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) of
the Centers for Disease Control and Prevention changed their recommendation for
influenza vaccination for the 2004-05 season to include universal vaccination for
all healthy children 6-23 months of age. METHODS: A self-administered survey was
distributed to a random sampling of family practitioners and pediatricians in
Chicago, IL. Questions were asked regarding demographics, current use of
influenza vaccines, and knowledge regarding influenza vaccines and influenza
infection in children. Answers were scored as correct based on published
literature and AAP/ACIP recommendations. RESULTS: During the 2002-2003 influenza
season, recommendation for influenza vaccination and perceived use for both
healthy children and children with a high-risk medical condition were both low.
The majority of physicians were not aware of the severity of influenza infection
in young children, could not correctly identify all contraindications to
receiving vaccination, did not know which children require two vaccinations, and
were not aware of the complications of influenza in children. CONCLUSIONS: To
achieve the goal of universal influenza vaccination coverage for the 2004-05
season for healthy children 6-23 months of age, physicians will need a greater
understanding of the severity of influenza illness in this age group coupled with
an increased knowledge of indications for vaccine administration.
PMID- 17038823
TI - Immunogenicity and tolerability of intradermal administration of an HCV E1-based
vaccine candidate in healthy volunteers and patients with resolved or ongoing
chronic HCV infection.
AB - The tolerability and immunogenicity of intradermal injections of a candidate HCV
vaccine, based on the E1 protein of the hepatitis C virus (HCV), was examined in
an exploratory study in healthy volunteers, in subjects with a history of
resolved HCV infection, and in patients suffering from therapy-resistant chronic
HCV. Sub-epidermal injection of three doses of 4 microg of non-adjuvanted E1
vaccine induced much weaker humoral and cellular immune responses in healthy
subjects and chronic HCV patients than the intramuscular administration of 20
microg E1 formulated on alum. However, in three subjects who cleared HCV
infection, intradermal administration of this low dose of E1 induced rapid and
clear anamnestic responses. These data demonstrate that E1-specific immune
responses can be induced in resolving HCV infections and that memory (B and T)
cells can be restimulated with suboptimal doses of E1 antigen.
PMID- 17038824
TI - Mechanism of adsorption of three recombinant Streptococcus pneumoniae (Sp)
vaccine antigens by an aluminum adjuvant.
AB - The adsorption of three Streptococcus pneumoniae (Sp) vaccine antigens by
aluminum-containing adjuvants was studied. The antigens showed high binding
affinity isotherms with aluminum hydroxide adjuvant described by the Langmuir
equation but virtually no binding to aluminum phosphate adjuvant. The effects of
ionic strength and ethylene glycol were evaluated to determine whether
electrostatic or hydrophobic interactions were responsible for the observed
binding to aluminum hydroxide, but no significant change in the adsorptive
capacity was observed at either high ionic strength nor high concentrations of
ethylene glycol for any of the antigens. This indicates that neither
electrostatic nor hydrophobic interactions appear to be responsible for the
observed binding, which means that ligand exchange may be the primary mechanism
for this interaction. Further studies to evaluate the ability to elute a Sp
antigen from aluminum hydroxide using fibrinogen (adsorptive coefficient 2.2
mL/microg) as a competitive protein resulted in evidence that Sp antigen follows
the trend that proteins with higher adsorptive coefficients are able to displace
those with lower adsorptive coefficients. It was also noted that the Sp antigens
and alpha-lactalbumin (adsorptive coefficient 1.8 mL/microg) have similar
adsorptive coefficients indicative of high affinity binding isotherms but do not
contain phosphate, which has previously been used to explain ligand exchange for
such proteins as alpha-casein and hepatitis B surface antigen (HBsAg). Further
investigations using alpha-lactalbumin as a model protein may elucidate the
binding interaction between the antigens in this study and aluminum adjuvants.
PMID- 17038825
TI - Safety concerns regarding combination vaccines. Perspective of select European
countries.
AB - This study explored health officials' perception of parental concern regarding
the safety of combination vaccines and its impact on policy decisions in
different European countries. Interviews were conducted with governmental and
nongovernmental health officials in the United Kingdom, France, Ireland and
Sweden over a four-month period. Parental concern regarding the safety of
combination vaccines was perceived to be prevalent in the United Kingdom, Ireland
and Sweden while no such concern was evident in France. The concern was limited
to the combined measles, mumps and rubella vaccine and its alleged causal
association with autism and did not carry over to other combined vaccines.
Although proposed by certain political groups, no policy changes regarding
combination vaccines were made in any study country.
PMID- 17038826
TI - A non-living nasal influenza vaccine can induce major humoral and cellular immune
responses in humans without the need for adjuvants.
AB - Twenty-eight healthy adult volunteers were immunized intranasally with an
inactivated whole-virus influenza vaccine based on the strain A/New
Caledonia/20/99 (H1N1), either in saline or mixed with formaldehyde-inactivated
Bordetella pertussis as a mucosal adjuvant, or in a thixotropic vehicle with
mucoadhesive properties. After four doses, all groups of vaccinees developed
significant IgG- and IgA-antibody responses, measured by ELISA, in respectively
serum and nasal secretions. None of the volunteers had demonstrable
hemagglutination inhibition (HAI) antibodies in serum before being immunized,
whereas more than 80% of them reached HAI titers>or=40, considered protective,
after immunizations. In addition, cellular immune responses, measured as
significant increases in CD4+ T-cell proliferation and granzyme B-producing
cytotoxic T-cells, were detected against the vaccine strain as well as against
heterologous virus strains (H3N2). However, no additive effect on these responses
could be demonstrated with use of B. pertussis or the thixotropic substance in
the present vaccines. It appeared, actually, that the mucoadhesive vehicle
containing the thixotropic substance was less efficient than were the two other
formulations. An influenza vaccine made as a simple particulate formulation of
inactivated virus, and given repeatedly onto the nasal mucosa, may thus be an
attractive alternative to currently available vaccines.
PMID- 17038828
TI - A meta-analysis of studies comparing the respiratory route with the subcutaneous
route of measles vaccine administration.
AB - The respiratory tract has been suggested as an optimal alternative site to target
measles vaccine delivery. We performed a meta-analysis to evaluate the efficacy
of measles vaccine administered through the respiratory route compared to the
subcutaneous route. We analyzed 20 reported results from 16 eligible studies.
Seroresponse was 4% higher amongst vaccinees in the respiratory group compared to
the subcutaneous group (M-H pooled RR = 1.04; 95% CI = 0.98-1.10). For vaccinees
over 9 months of age, seroresponse was 15% higher in the respiratory group (M-H
pooled RR = 1.15; 95% CI = 1.08 to 1.17). When Edmonston Zagreb (EZ) strain was
used, the vaccine was found to be neither more nor less efficacious when
administered through respiratory route (M-H pooled RR=1.00; 95% CI = 0.94 to
1.08). Seroresponse in the vaccinees receiving aerosol measles vaccine was 10%
higher (M-H pooled RR = 1.10, 95% CI = 1.04-1.17) compared to those who received
measles vaccine through the subcutaneous route. Seroresponse due to aerosolized
EZ vaccine was 9% higher than subcutaneous EZ vaccine (M-H pooled RR = 1.09; 95%
CI = 1.02-1.16). The seroresponse among seropositive vaccinees was 60% higher (M
H RR = 1.60; 95% CI = 1.40 to 1.80). The results suggest that the respiratory
route of delivery of measles vaccine is at least as efficacious as measles
vaccine administered through the subcutaneous route. However, more research is
required on standardization of dosage, administration equipments, efficacy, and
safety of respiratory (aerosol) route of administration of measles vaccine.
PMID- 17038827
TI - Phase I, randomized, controlled trial to study the reactogenicity and
immunogenicity of a nasal, inactivated trivalent influenza virus vaccine in
healthy adults.
AB - We performed a randomized, placebo-controlled, dose-escalating clinical trial to
evaluate the safety and immunogenicity of an inactivated, split virion,
trivalent, nasal influenza vaccine using lipid/polysaccharide molecules as
carriers. A total of 64 adults (mean age 29; range 19-69 years) were randomly
allocated to receive a mixture of lipid/polysaccharide carrier molecules and 7.5,
15, or 30 microg hemagglutinin antigen of each of the three influenza strains
(A/Johannesburg/82/96 [H1N1], A/Nanchang/933/95 [H3N2], B/Harbin/07/94) or
placebo via nasal spray on two occasions separated by 28 days. Adverse events
were assessed immediately after immunization and for 14 days after each dose.
Nasal and serum antibodies were measured before and two weeks after each dose.
All but three participants completed the study; no withdrawals were because of
adverse events. Adverse events were similar immediately after immunization except
for anterior nasal dripping after the first dose which was more common in the
combined vaccine groups (64.4%) than in the placebo group (31.3%; p < 0.05). A
similar trend was observed after the second dose. Nasal dripping was also more
common in the first two days after immunization in the vaccine groups than the
placebo group (31.3%-50% vs. 0%) with no difference with increasing vaccine dose.
The vaccine elicited a modest serum antibody response against all three viruses,
with the highest dose eliciting the highest serum antibody levels. In contrast,
significant nasal antibody rises were observed for all three viruses; again, the
30 microg group achieved the highest mucosal antibody levels at the earliest time
points. We conclude that this trivalent, split virion, inactivated nasal
influenza vaccine formulated with lipid/polysaccharide molecule carriers is well
tolerated and modestly immunogenic in healthy adults.
PMID- 17038829
TI - Exercise-induced serum enzyme elevations confounding the evaluation of
investigational drug toxicity. Report of two cases in a vaccine trial.
AB - Two subjects developed marked elevations in creatine kinase and other serum
enzymes associated with mild myalgia during a randomized, double-blind,
controlled Phase 1 clinical trial of an investigational live, attenuated vaccine
against West Nile virus (ChimeriVax-WN02). One subject had received ChimeriVax
WN02 while the other subject was enrolled in an active control group and received
licensed yellow fever 17D vaccine (YF-VAX). Subsequently, the clinical trial was
interrupted, and an investigation was begun to evaluate the enzyme abnormalities.
As daily serum samples were collected for determination of quantitative viremia,
it was possible to define the enzyme elevations with precision and to relate
these elevations to physical activity of the subjects, symptoms, and virological
and serological measurements. Evaluation of both subjects clearly showed that
skeletal muscle injury, and not cardiac or hepatic dysfunction, was responsible
for the biochemical abnormalities. This investigation also implicated strenuous
exercise as the cause of the apparent muscle injury rather than the study
vaccines. As a result of this experience, subjects engaged in future early-stage
trials of these live, attenuated viral vaccines will be advised not to engage in
contact sports or new or enhanced exercise regimens for which they are not
trained or conditioned. The inclusion of placebo control arm (in lieu of or
addition to an active vaccine control) will also be useful in differentiating
causally related serum enzyme elevations.
PMID- 17038830
TI - Role of neutralizing antibodies in protective immunity against HIV.
AB - HIV continues to be a major health problem world wide, however the situation is
particularly serious in Asian and Sub-Saharan countries. Therefore, development
of an effective HIV vaccine could help to reduce the severity of the disease and
prevent infection. Over the last two decades significant efforts have been made
towards inducing potent humoral and cellular immune responses by vaccination,
however antibodies and CTL responses alone are likely not sufficient for inducing
sterilizing immunity or long-term control of viral replication. Therefore, it is
generally believed that both humoral and cellular responses will be needed for an
effective HIV vaccine. In support of humoral immunity, monoclonal antibodies that
recognize critical neutralizing epitopes have shown to be effective at passive
transfer experiments in conferring protection against challenge infection.
However, antibodies to similar epitope specificities are difficult to induce by
vaccination. Therefore, optimization of Env structure is needed for exposing
appropriate neutralizing epitopes and masking non-neutralizing epitopes. Since
the crystal structure of the core of Env glycoprotein has been solved, efforts
are in progress to design novel Env immunogens that may induce effective
neutralizing responses. Furthermore, there are HIV-1 strains that are resistant
to neutralization by monoclonal antibodies, yet neutralized by pooled sera from
HIV-1 patients. Therefore, efforts should be made to identify these novel
epitopes and to design strategies to incorporate them in potential vaccines. To
facilitate comparative evaluation of vaccine immunogens for their ability to
induce cross clade neutralizing antibodies, efforts should be made to use
standardized neutralization assays and standard virus panels. Once potent HIV Env
structure have been identified, their effectiveness may be enhanced through the
use of adjuvants, delivery systems and prime and boost strategies to improve the
quality and magnitude of neutralizing responses.
PMID- 17038831
TI - Characterization of the protein content of a meningococcal outer membrane vesicle
vaccine by polyacrylamide gel electrophoresis and mass spectrometry.
AB - The development and evaluation of outer membrane vesicles as vaccines against
meningococcal disease has been carried out for more than two decades. Although
such vaccines have limitations and are not widely licensed, they continue to be
used to disrupt clonal outbreaks caused by group B meningococci and a wealth of
information is now available from large-scale clinical studies. One dimensional
polyacrylamide gel electrophoresis and semi-quantitative measurement of the major
proteins is one method used to evaluate and control these products. However, it
is often difficult to determine exactly which bands on a one dimensional gel
correspond to the key antigens whose presence must be demonstrated for control
and lot release. We have therefore carried out mass spectrometric analyses of
outer membrane vesicle vaccine samples to definitively identify the bands
containing seven key antigens: Omp85, FetA, PorA, PorB, RmpM, OpcA and NspA. An
additional 33 proteins present in the vaccine were also identified and this
information will be useful both for future quality control and for the
interpretation of data from vaccine trials.
PMID- 17038832
TI - Medical burden of respiratory syncytial virus and parainfluenza virus type 3
infection among US children. Implications for design of vaccine trials.
AB - Respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) are two
leading causes of lower respiratory illness (LRI) in infants. Many efforts have
been directed to develop vaccines against these two viruses. Licensure of new
vaccines includes three phases of clinical trials to evaluate safety,
immunogenicity, and efficacy. To design an efficacy trial, age-specific incidence
rates of suitable clinical endpoints need to be available. In this review,
historical data are summarized to estimate the age-specific rates of acute
respiratory illness (ARI), LRI, and hospitalization caused by RSV and PIV3 among
US children <5 years of age. Nation-wide data are available for hospitalization
but not ARI and LRI. Age-specific rates of RSV and PIV3-related ARI or LRI can
vary 9-fold or 5-fold, respectively, in different studies conducted in different
populations using different clinical and laboratory definitions. The annual
medical burden for RSV and PIV3 in children <5 was estimated respectively to be
about 4.19 and 3.24 million cases of medically-attended ARI, 2.1 and 1.08 million
cases of LRI, and 113 and 29 thousand cases of hospitalization, respectively. The
impact of three important variables including age at vaccination, clinical
endpoints, and laboratory diagnosis in designing efficacy trials is discussed. A
RSV vaccine which is safe and effective in the first six months of life is
optimal to reduce the severe disease burden of LRI and hospitalization, however,
interference of maternal antibody may reduce vaccine efficacy in this age group.
LRI occurs more frequently than hospitalization and may be the most feasible
clinical endpoint for designing efficacy trials. Since age-specific rates of RSV
and PIV3-related LRI can vary significantly in different populations, collecting
age-specific LRI rates in phase 1 and 2 trials to further understand this
variability appears warranted.
PMID- 17038833
TI - Free-riding, fairness and the rights of minority groups in exemption from
mandatory childhood vaccination.
AB - The authority of government to require participation in mandatory childhood
vaccination programs may not target specific groups for either participation or
exemption on a discriminatory basis. This poses difficulties when allowing
religious or philosophical exemptions to mandatory vaccination, because certain
groups are more likely to appeal for exemption. Avoiding loss of herd immunity,
then, may require either discrimination against these groups by disallowing an
exemption option that is available to others, or by denying the good of an
exemption option to the entire population because of the action of certain
groups. To avoid this unacceptable choice, steps must be taken now to more
stringently enforce exemption requirements.
PMID- 17038834
TI - A DNA-based vaccine for the prevention of human cytomegalovirus-associated
diseases.
AB - Multiple lines of evidence indicate that in the transplant population human
cytomegalovirus (HCMV) infection and its associated diseases are controlled by
humoral and cellular immune responses similar to those that arise in
asymptomatic, healthy individuals during a naturally-acquired infection. The
dominant antibody response to HCMV is to the major surface glycoprotein B (gB)
and the dominant cellular immune response is to the tegument phosphoprotein
(pp65). We propose that an immunotherapeutic plasmid DNA (pDNA) vaccination
approach that induces the requisite responses to major immunological targets of
HCMV may provide relief from HCMV-associated diseases in the transplant setting.
We have developed gene-based immunotherapeutic products consisting of pDNAs
encoding gB and pp65 of HCMV. When tested individually in mice, both pDNAs were
highly immunogenic. Relative to vaccination with either gB or pp65 pDNA delivered
alone, vaccination with gB and pp65 pDNAs delivered together in phosphate
buffered saline (PBS) elicited reduced antibody and T cell responses to each
antigen. Formulating this bivalent vaccine with a poloxamer-based delivery system
(VF-P1205-02A), however, significantly increased the antigen-specific immune
responses relative to those induced with the bivalent vaccine in PBS, and
completely abrogated the decrease in pp65-specific T cell responses observed in
mice covaccinated with the pDNAs in PBS. Based on these data, and a favorable
safety and toxicity profile in preclinical studies, the bivalent HCMV vaccine
consisting of gB and pp65 pDNAs delivered with VF-P1205-02A has advanced to human
clinical trials.
PMID- 17038836
TI - Colorectal cancer prevention and screening: a Health Belief Model-based research
study to increase disease awareness.
AB - The purpose of this quasi-experimental study was to evaluate the effects of a
Health Belief Model-based colorectal cancer (CRC) education session on adult
participants. Education sessions were conducted at a site chosen by the
participants, such as their homes, in a mid-sized, mid-Western city. Thirty-one
Caucasian adults participated. Eleven were men (35%) and 20 were women (65%).
Study results reveal that the education sessions were an effective way to promote
awareness of CRC prevention and screening. The participants' responses reflected
a positive and significant (p < .0001) improvement in all areas except beliefs
regarding maintenance of a healthy weight (p = .0574). The greatest effect was on
men, current smokers, and those with a high school education or less. Education
sessions were equally effective for auditory and visual learners. The 31
participants planned to share the information with at least 32 other individuals.
The participants acquired an increased awareness of CRC prevention and screening.
Willingness to discuss CRC after the education sessions may be significant,
especially because the others may, in turn, share the information. Nurses need to
be aware of CRC screening guidelines. The impact of patient teaching on this
health promotion effort may reach beyond the patients who were in contact with
the nurses. Public awareness might be further increased when patients share this
information with others.
PMID- 17038837
TI - Physicians, nonphysician healthcare providers, and patients communicating in
hepatitis C: an in-office sociolinguistic study.
AB - In-office conversations about hepatitis C can impact patients' perceptions of
outcomes, as well as medication adherence. This study analyzed interactions
between physicians, nonphysician healthcare providers (including nurses), and
patients with hepatitis C virus infection in order to examine differences based
on number and type of providers participating. Gastroenterologists, nonphysician
healthcare providers, and patients with hepatitis C virus infection were video-
and audio-recorded during regularly scheduled visits. Recordings were transcribed
and analyzed using validated sociolinguistic techniques. Thirty-four visits took
place with a physician only, 4 with a nonphysician healthcare provider only, and
25 with both providers (9 concurrent and 16 consecutive). Differences among the
participant schema included visit length, patient "talk-time," and motivation
provided. When providers saw patients consecutively, differing information was
sometimes provided. In visits where providers saw the patient concurrently,
competing authority between providers and exclusion of the patient through use of
medical jargon were obstacles to ideal communication. Differences in hepatitis C
related interactions based on the number and type of participants suggest
opportunities for improved communication. In visits with multiple providers,
physicians and nurses should attempt to ensure that they (a) avoid supplying
differing information, (b) present a "unified front" to avoid competing
authority, and (c) minimize the use of medical jargon, which excludes patients
from participating in their own healthcare.
PMID- 17038838
TI - Nurse-administered propofol sedation: a review of current evidence.
AB - This article highlights a highly controversial practice issue referred to as
nurse-administered propofol sedation, which affects registered nurses as well as
advanced practice nurses in many different practice settings across the United
States. Amid varied advice from professional organizations and state licensing
boards, a thorough and systematic review of the current evidence provides insight
into the question of safety associated with the practice. The evidence examined
includes position statements from professional organizations and state boards,
information from the United States Food and Drug Administration and the Joint
Commission on Accreditation of Healthcare Organizations, and published research
since 1999. The body of evidence demonstrates diverse positions; however, the
empirical evidence in the author's opinion unanimously supports nurse
administered propofol sedation as a safe practice in nonintubated adult patients.
Under research conditions, participants had a low incidence of untoward events
and were adequately rescued with no intubations required and no deaths reported.
PMID- 17038840
TI - Clinical applications of argon plasma coagulation in endoscopy.
AB - The argon plasma coagulator is a device used for noncontact thermal coagulation
of tissue. The device was first used in open and laparoscopic surgical procedures
and in 1991 was adapted for use in endoscopy. Since then, argon plasma
coagulation has expanded its clinical applications in the treatment of various
gastrointestinal conditions. The endoscopy nurse plays an important role in the
care of patients before, during, and after argon plasma coagulation treatment.
This article reviews the principles and components of the argon plasma
coagulator, and provides a summary of the various clinical applications, patient
safety practices, and potential complications of argon plasma coagulation
therapy.
PMID- 17038842
TI - Reprocessing of endoscopic accessories and valves.
PMID- 17038843
TI - Reprocessing of water bottles used during endoscopy.
PMID- 17038844
TI - A photodynamic therapy for ampullary cancer.
AB - This case study describes the application of photodynamic therapy for palliative
care in an older patient with inoperable pancreatic cancer. For this procedure, a
photosensitizing drug is applied endoscopically followed by a laser light beam
that is directed onto the tumor, facilitating a photochemical reaction. The
photodynamic drug becomes cytotoxic in this process, working to destroy the
neoplastic tissue. In this case study, the procedure was performed by an
endoscopic surgeon in the operating room at a large Midwestern academic medical
center. The details of application of photodynamic laser therapy, which
frequently alleviates discomfort for patients who otherwise have few options, is
described for this patient.
PMID- 17038845
TI - Herbs, supplements, and nonprescribed drugs.
PMID- 17038846
TI - Ergonomics for the endoscope.
PMID- 17038847
TI - An update on advanced/specialist roles in ireland.
PMID- 17038848
TI - Trading places.
PMID- 17038849
TI - Larry's story.
PMID- 17038852
TI - A word to the wise: tips for the first-time traveler.
PMID- 17038853
TI - How OTs and PTs can help stroke patients recover.
PMID- 17038855
TI - Integrating Iyengar yoga into rehab for spinal cord injury.
PMID- 17038868
TI - Sirolimus--challenging current perspectives.
AB - Sirolimus is a potent immunosuppressant drug with a novel mechanism of action. It
inhibits the mammalian target of rapamycin (mTOR) and blocks the cell cycle of
various cell types, including T- and B-lymphocytes. Sirolimus is widely used as a
maintenance immunosuppressive agent in organ transplantation. Also, a potentially
benefit of this valuable drug in some immunologic and malignant diseases is
currently under scrutiny.Classical side effects: hematological (anaemia,
leucopenia, thrombocytopenia), hypercholesterolemia, arthralgias, extremity
oedema and impaired wound healing have been frequently associated with the use of
sirolimus. Additionally with its increased use, transplant professionals are
encountering a variety of previously unreported and potentially more severe side
effects.Here, we review the most recent data on sirolimus unexpected side effects
(with an emphasis on pulmonary and renal toxicity), its use in renal
transplantation and its new potential therapeutic indications (chronic
glomerulopathies, polycystic kidney disease, different types of cancer). A brief
description of the current knowledge of sirolimus therapeutic drug monitoring,
methods of analysis, pharmacokinetics and drug interactions with calcineurin
inhibitors is also included.
PMID- 17038869
TI - TDM grand rounds: neonatal nicotine withdrawal syndrome in an infant prenatally
and postnatally exposed to heavy cigarette smoke.
AB - A heavy smoking, lactating mother delivered a baby that exhibited spontaneous
tremors, fluctuations of muscular rigidity, and opisthotonus at 48 hours of life.
Although the symptoms did not disappear within the following days, they could be
controlled by swaddling or wrapping the baby in a blanket. The absence of any
other etiology generated a suspicion of prenatal exposure to heavy tobacco smoke
and potential neonatal nicotine withdrawal syndrome. This diagnosis was supported
by extremely high concentration of hair nicotine and cotinine in the infant's
hair and in different segments of maternal hair. The presence of non-negligible
amounts of nicotine and cotinine in breast milk confirmed that the mother did not
quit smoking after delivery, despite her reports. The breast-fed newborn
continued to have 3 to 4 crises of spontaneous tremors and alternant muscular
rigidity per day for a month. More studies are needed to establish neonatal
nicotine withdrawal.
PMID- 17038870
TI - The use of TDM data to assess the validity of defined daily doses of
antiepileptics: a comparison between a Czech and Swedish University Hospital.
AB - Prescribed daily doses (PDDs) of antiepileptic drugs (AED) (N03A ATC group) were
recorded for drugs used in monotherapy or in combination therapy in the
University Hospitals in Ostrava, Czech Republic and Huddinge, Sweden. Plasma
concentrations were used as an indicator of the quality of treatment. PDDs were
compared with the defined daily doses (DDDs) suggested by WHO in the ATC/DDD
index 2005. Request and reply forms for therapeutic drug monitoring (TDM) were
used as a source of mean PDDs. The study included 2,824 adult out- and in
patients in Huddinge treated from 1995 to 1999 and 1,268 out-patients treated in
Ostrava from 1993 to 2004. The differences in PDD were tested by Student's t
test. Mean values of PDD were used when patients were examined more than once.
Doses given in mono- and polytherapy were compared. Mean PDDs (in mg) in mono
/polytherapy in Huddinge and Ostrava were as follows (DDDs in parenthesis):
carbamazepine 588/842 and 618/770 (1,000), clonazepam 3.0/2.5 and 3.4/2.4 (8),
phenytoin 278/314 and 291/288 (300), gabapentin -/1,533 and -/921 (1,800),
lamotrigine 228/228 and 216/195 (300), phenobarbital 90/75 and 183/117 (100),
vigabatrin -/1,794 and -/1,259 (2,000), valproic acid 1,139/1,476 and 814/950
(1,500). The PDDs of most of the AEDs were lower than the DDDs with the
exceptions for valproic acid (Huddinge, in polytherapy only), phenytoin, for
which PDDs and DDDs were very close, and phenobarbital for which they were
similar in Huddinge but higher in Ostrava. PDDs in monotherapy were only slightly
lower than in combination therapy. Patients with plasma concentrations within the
therapeutic range were usually treated with slightly higher doses than the
remainder. In general, plasma concentrations tended to be in the low therapeutic
range. The differences in PDDs between hospitals were significant in the case of
valproic acid (P < 0.001), phenobarbital (except monotherapy within), vigabatrin,
and gabapentin (P < 0.01), and carbamazepine (in monotherapy P < 0.05,
polytherapy P < 0.01). Our data suggest that the DDDs of AEDs should be
reconsidered as, in the majority of cases, they appear to be too high.
PMID- 17038871
TI - Therapeutic monitoring of antiepileptic drugs: a comparison between a Czech and a
Swedish University Hospital.
AB - Plasma concentrations obtained during routine therapeutic monitoring of
antiepileptic drugs (AED) (N03A ATC group) were compared in patients treated with
one or several AED in the University Hospitals in Ostrava, Czech Republic and
Huddinge, Sweden. Request and reply forms for therapeutic drug monitoring (TDM)
were used as a source of mean plasma concentrations (PC). The study included
2,824 adult out- and inpatients in Huddinge treated from 1995 to 1999 and 1,268
outpatients treated in Ostrava from 1993 to 2004. PC of valproic acid in Huddinge
and all AED except clonazepam in Ostrava were analyzed with gas-liquid
chromatography. Plasma concentrations of clonazepam in Ostrava and all AED except
valproic acid in Huddinge were analyzed by HPLC. The differences in PC were
tested by Student's t-test. Chi(2) method was used for the differences in the
distribution of PC relative to the therapeutic window. The mean plasma
concentrations generally reached the apparent therapeutic ranges but were below
the range in the cases of phenytoin monotherapy in both hospitals, and
clonazepam, phenobarbital and phenytoin in polytherapy in Ostrava. In monotherapy
33% of the analyses showed sub-therapeutic concentrations in Huddinge, compared
to 38% in Ostrava. Eight percent of the analyses showed potentially toxic
concentrations in Huddinge, but only 3% in Ostrava. The highest number of sub
therapeutic concentrations was detected for phenytoin in both hospitals: 59% in
Huddinge, 78% in Ostrava. In polytherapy only slight differences between the
hospitals were found. PC/dose ratios were significantly lower in polytherapy than
in monotherapy for carbamazepine and valproic acid in both hospitals. In contrast
a higher PC/dose ratio was found in polytherapy for phenytoin in both cohorts and
for lamotrigine in Ostrava. Drug treatment of epilepsy in our two hospitals is
surprisingly similar in terms of achieved plasma concentrations, in spite of
socioeconomic and cultural differences between our two countries. This may be
explained by the long experience with TDM in both hospitals, which has the
inherent capacity to promote evidence based drug therapy.
PMID- 17038872
TI - Effect of adjunctive lamotrigine treatment on the plasma concentrations of
clozapine, risperidone and olanzapine in patients with schizophrenia or bipolar
disorder.
AB - The effect of lamotrigine on the steady-state plasma concentrations of the
atypical antipsychotics clozapine, olanzapine, and risperidone was investigated
in patients with schizophrenia or bipolar disorder stabilized on chronic
treatment with clozapine (200-500 mg/day; n = 11), risperidone (3-6 mg/day; n =
10) or olanzapine (10-20 mg/day; n = 14)). Lamotrigine was titrated up to a final
dosage of 200 mg/day over 8 weeks, and pharmacokinetic assessments were made at
baseline and during treatment weeks 6 and 10, at lamotrigine dosages of 100 and
200 mg/day respectively. The plasma concentrations of clozapine, norclozapine,
risperidone, and 9-hydroxy-risperidone did not change significantly during
treatment with lamotrigine. The mean plasma concentrations of olanzapine were 31
+/- 7 ng/mL at baseline, 32 +/- 7 ng/mL at week 6, and 36 +/- 9 ng/mL at week 10,
the difference between week 10 and baseline being statistically significant (P <
0.05). Adjunctive lamotrigine therapy was well tolerated in all groups. These
findings indicate that lamotrigine, at the dosages recommended for use as a mood
stabilizer, does not affect the plasma levels of clozapine, risperidone, and
their active metabolites. The modest elevation in plasma olanzapine
concentration, possibly due to inhibition of UGT1A4-mediated olanzapine
glucuronidation, is unlikely to be of clinical significance.
PMID- 17038873
TI - Determination of lamotrigine and its metabolites in human plasma by liquid
chromatography-mass spectrometry.
AB - A method based on electrospray ionization liquid chromatography-mass spectrometry
was developed for the quantitative determination of lamotrigine and three of its
reported metabolites, lamotrigine-2-N-glucuronide, lamotrigine-2-N-methyl, and
lamotrigine-2-N-oxide in human blood plasma. The method utilized sample
preparation by precipitation of proteins with acetonitrile, chromatographic
separation on a reversed-phase system by gradient elution, and monitoring of the
protonated molecular ions. Two internal standards, 3,5-diamino-6-(2
methoxyphenyl)-1,2,4-triazine and morphine-3-glucuronide-D3, were utilized to
achieve precise quantification. The method validation comprised a demonstration
of an agreement in the quantification of lamotrigine with that of a routine HPLC
UV method. The limits of detection were between 0.05 and 0.16 micromol/L. The
method was employed for the measurement of clinical samples collected from 55
patients in steady-state prior to the dose intake (trough level). Lamotrigine and
the 2-N-glucuronide were typically detected, while the N-methyl and N-oxide
metabolites were detected only rarely. The median lamotrigine plasma level was
24.0 micromol/L (range, 4.3 to 64 micromol/L), the median 2-N-glucuronide level
was 2.4 micromol/L (range, <0.05 to 24 micromol/L), and the median lamotrigine 2
N-glucuronide/lamotrigine ratio was 0.11 (range, <0.01 to 0.64). In conclusion,
this liquid chromatographic-mass spectrometric method is suitable for
simultaneous determination of lamotrigine and its metabolites in human plasma.
PMID- 17038874
TI - Determination of inosine monophosphate dehydrogenase activity in human CD4+ cells
isolated from whole blood during mycophenolic acid therapy.
AB - Inosine 5'-monophosphate dehydrogenase (IMPDH) is an established target in
immunosuppression following organ transplantation. In lymphocytes, reversible
inhibition of this enzyme by mycophenolic acid (MPA) results in reduced
production of guanine and deoxyguanine nucleotides and thereby retarded
proliferation of activated cells. In order to examine MPA pharmacodynamics in
renal allograft recipients, the authors have developed an assay for the
determination of IMPDH activity in CD4+ cells directly isolated from a small
blood volume. Paramagnetic beads coated with anti-CD4 antibodies were utilized
for the cell isolation. The intracellular MPA concentration was restored by
incubating the cells in microfiltrated plasma from the original sample. Inosine
5'-monophosphate (IMP; substrate) and nicotine adenine dinucleotide (NAD; co
factor) were added to cell lysates, and IMPDH activity was quantified as the
xanthosine 5'-monophosphate (XMP) production rate (pmol/10 cells/min) determined
by liquid chromatography after hydrolytic cleavage to xanthine. The reaction
kinetics were saturated with IMP and NAD concentrations of 1.79 micromol/L and
0.38 micromol/L, respectively. The production rate was linear in the interval
0.13 to 8.7 pmol XMP/min. Total interseries CVs based on seven replicates at each
MPA concentration 0, 2.2, and 8.6 microg/mL were 25%, 16%, and 13%, respectively.
When a single 1 gram mycophenolate mofetil dose was administered to a healthy
individual, the measured IMPDH activity was 13% of predose value at the MPA peak
concentration. The present assay allows reliable determination of IMPDH activity
in CD4+ cells during MPA exposure, reducing the potential influence of sample
preparation on the measured enzyme activity to a minimum. The assay may be
applied to assess MPA pharmacodynamics during immunosuppressive treatment,
maintaining the influence of intracellular MPA on the IMPDH activity.
PMID- 17038875
TI - Apparent clearance of sirolimus in heart transplant recipients: impact of primary
diagnosis and serum lipids.
AB - The study was aimed to identify factors affecting sirolimus apparent clearance
(CL/F) in de novo heart transplant recipients using a population pharmacokinetic
approach. A total of 31 patients (7 female and 24 male) originally included in a
formal clinical trial, contributed 524 sirolimus blood concentrations with the
time after dose ranging from 11.08 to 31.83 hours. Sirolimus concentrations were
measured using liquid chromatography-tandem mass spectrometry and data analysis
was carried out using NONMEM (Globomax LLC, Hanover, MD) software. Factors
screened included age, weight, gender, primary diagnosis, biochemical and
hematological indices, cyclosporine dose, days post-transplant and potential
interacting medications. The predictive performance of the final model was
evaluated using a data-splitting method. Sirolimus apparent clearance (CL/F) was
decreased by 20.8% for every 100-mg increase in cyclosporine daily dose and was
62.1% lower in patients with primary diagnosis of ischemic heart disease (IHD).
Sirolimus apparent clearance was 37.8% lower when triglyceride was greater than 2
mmol/L. Based on the final model, the average values for sirolimus CL/F and
apparent volume of distribution were 7.09 and 1,350 L/h, respectively. Inter
subject variability in CL/F was 27.5% and residual random error was 24.1%. This
study identified cyclosporine dose, hypertriglyceridemia and primary diagnosis of
IHD as the most important factors affecting sirolimus CL/F. This information may
assist in dose individualization of sirolimus in transplant recipients.
PMID- 17038876
TI - Validation of an abbreviated pharmacokinetic profile for the estimation of
mycophenolic acid exposure in pediatric renal transplant recipients.
AB - The pharmacokinetics of mycophenolic acid (MPA), the active moiety of the
immunosuppressant mycophenolate mofetil (MMF), exhibits large inter-individual
variability. Concentration-controlled dosing of MMF based on therapeutic drug
monitoring may therefore be advantageous compared to a fixed-dose regimen.
Because full AUC(0-12) monitoring is not practical and predose MPA concentrations
correlate only moderately with the corresponding AUC(0-12), the estimation of MPA
exposure by a limited sampling strategy has been suggested. However, before such
an algorithm is transferred to clinical practice, it is compulsory to
prospectively validate it in a different data set, in order to avoid biased
results. The aim of this investigation was therefore to prospectively validate an
algorithm based on an abbreviated pharmacokinetic (PK) profile for the estimation
of MPA exposure in 54 pediatric renal transplant recipients (169 PK profiles) on
MMF in conjunction with CsA and prednisone on a second data set in a different
group of patients with a similar immunosuppressive regimen (25 patients, 119 PK
profiles). An algorithm based on three PK sampling timepoints during the first 2
hours after MMF dosing (estimated AUC(0-12) = 18.6 + 4.3 x C(0) + 0.54 x C(0.5) +
2.15 x C(2)) was able to predict the corresponding MPA-AUC(0-12) with a low
percentage prediction error (10.7%) and an acceptable coefficient of
determination (r = 0.76). The performance of this algorithm was comparable among
different pediatric age groups. By ROC curve analysis, the calculated MPA-AUC(0
12) based on this algorithm was able to differentiate between rejecters and non
rejecters with a comparable prognostic sensitivity (66.7%) and specificity
(61.9%) as the full-time MPA-AUC(0-12). In conclusion, the use of this validated
algorithm for the estimation of MPA exposure based on a limited sampling strategy
during the first 2 hours after MMF dosing has the potential to optimize MMF
therapy in pediatric renal transplant recipients.
PMID- 17038877
TI - CEDIA mycophenolic acid assay compared with HPLC-UV in specimens from transplant
recipients.
AB - Routine monitoring of mycophenolic acid (MPA) has been accepted as an essential
tool in the management of this therapy in transplant recipients. The availability
of simple, sensitive assays that measure MPA in plasma permits individualization
of dosing regimens according to pharmacokinetic principles. We report the results
of an evaluation of the CEDIA Mycophenolic Acid Immunoassay (Microgenics
Corporation, Fremont, California) for the measurement of plasma MPA
concentrations in a range of transplant indications and compare its performance
and specificity to an established HPLC/UV method. Precision and accuracy were
determined both within and between runs using the quality control materials
provided with the CEDIA MPA assay, which produced within run (n = 21)
coefficients of variation (CV%) and biases of less than 5%. The between run
analyses, performed over consecutive days following daily calibration of the
assay, showed CVs and biases of less than 7%. Routine patient samples (n = 298)
from 142 patients of varying transplant type were analyzed using the CEDIA MPA
kit and HPLC/UV methods. Regression analysis of the patient samples gave an
equation of CEDIA = 1.18 HPLC/UV + 0.45 (r = 0.83). According to the
manufacturer's product information, there is 192% cross reactivity with the
active mycophenolate acyl glucuronide. The data presented suggest that the CEDIA
MPA immunoassay, run on the Hitachi 911 analyzer, over-estimates plasma MPA
concentrations with a magnitude that is influenced by transplant type. Hence,
users must interpret the immunoassay results with caution and not assume that the
metabolite fraction is constant in recipients of the same organ type or in
different organ transplant populations.
PMID- 17038878
TI - Is C2 monitoring or another limited sampling strategy superior to C0 monitoring
in improving clinical outcomes in adult liver transplant recipients?
AB - Cyclosporine (CsA) has had a major impact on the process and success of solid
organ transplantation. Early in the use of CsA, therapeutic monitoring using the
predose (trough, or C0) concentration became the standard of care. However, there
are complications with the use of C0 monitoring that have only partly been
mitigated with the advent of the micro-emulsion formulation (CsA-ME). More
recently, limited sampling strategies (LSSs) for measuring the area under the CsA
concentration-time curve (AUC) have been investigated to improve the monitoring
of CsA post-transplantation. Many centres now routinely monitor CsA therapy using
the concentration at 2 hours postdose (C2). In this paper the strength of the
evidence for C2 (or other LSSs) relative to C0 monitoring of CsA-ME for improving
clinically important outcomes in liver transplant patients is critically
examined. Additionally, gaps in the literature are identified and recommendations
are made for clinical research that could be done to provide more definitive
evidence for the use of C2 or other LSSs in monitoring liver transplant patients.
PMID- 17038879
TI - Mycophenolic acid formulation affects cyclosporine pharmacokinetics in stable
kidney transplant recipients.
AB - A novel monitoring strategy based on the blood concentration at two hours post
dose (C2) has been recently proposed for the assessment of cyclosporine (CsA)
absorption and daily exposure, and therapeutic windows for C2 levels have been
identified. These guidelines have been derived from patients given mycophenolate
mofetil (MMF) or azathioprine, and never tested in those treated with the enteric
coated formulation of mycophenolic acid (EC-MPS). The authors have compared full
CsA pharmacokinetic evaluations in 12 kidney transplant recipients given EC-MPS
with those from 20 patients on MMF at months 6, 12, 18 and 24 postsurgery. At
month 6 postsurgery, patients on EC-MPS had a shift to the right in the CsA peak
concentration as compared to that in patients given MMF, an effect associated
with significant differences in CsA Tmax (1.9 +/- 0.3 h vs. 1.5 +/- 0.6 h, P <
0.05), C2 (988 +/- 259 vs. 720 +/- 214 ng/mL, P < 0.01), and C3 levels (539 +/-
119 vs. 435 +/- 119 ng/mL, P < 0.05). Interestingly, the authors found that the
majority of patients on EC-MPS had CsA peaking at 2-h postdosing, whereas most of
patients on MMF had CsA Cmax at 1 h. Similar results were observed also at months
12, 18, and 24 postsurgery. These findings indicate that the pharmacokinetics of
CsA is significantly affected by the concomitant administration of different MPA
formulations. This would imply the need of specific algorithms to adequately
estimate CsA dose adjustment in patients given, in addition to CsA, EC-MPS or
MMF.
PMID- 17038880
TI - A retrospective TDM database analysis of interpatient variability in the
pharmacokinetics of lopinavir in HIV-infected adults.
AB - Lopinavir is one of the most-widely used protease inhibitors in the treatment of
HIV-1 infected patients. Concentration-effect relationships have been described
for both antiviral activity and toxicity. Less is known about patient
characteristics that may determine interpatient variability in lopinavir plasma
concentrations. A database was created containing all Therapeutic Drug Monitoring
(TDM) results collected at our Department. Patients were included if they were
using lopinavir twice daily for at least two weeks; subjects who were known to be
nonadherent (based on either a lopinavir concentration <0.2 mg/L or suspected by
the physician) were excluded. Demographic data were collected from TDM
application forms and patient charts. Patients attending one of the 22 HIV
treatment centers in The Netherlands. The Department of Clinical Pharmacy is a
national referral center for TDM of antiretroviral agents. Lopinavir
concentration ratios (CRs) were calculated for each patient by dividing the
individual plasma concentration by the time-adjusted population value.
Relationships with lopinavir CRs were tested using regression analysis and
analysis of variance. A total of 802 patients were included (607 males; 150
females; 45 unknown). The age and body weight of the patients ranged from 18 to
74 years (mean 42) and 42 to 121 kg (mean 72), respectively. Race was known for
756 persons: Caucasian 76%, African 18% and Asian 6%. The median (+ interquartile
range, IQR) lopinavir CR was 0.98 (IQR: 0.67-1.31). Body weight showed an inverse
relationship with lopinavir CR (F = 23.1; P < 0.001). Age was not related with
lopinavir CR (P = 0.99). Female patients had a significantly higher lopinavir CR
than males: 1.18 vs. 1.03 (P = 0.005); race was not associated with differences
in lopinavir CR. In a multivariate regression analysis body weight, but not
gender, remained significantly related to lopinavir CR. Body weight is the only
demographic factor that could be related to lopinavir exposure; clinicians should
be alert for an increased risk of suboptimal antiviral efficacy in patients with
high body weight, and for an increased risk of toxicity in patients with a low
body weight.
PMID- 17038881
TI - Pharmacokinetics of intravenous rifampicin (rifampin) in neonates.
AB - Few reports have addressed neonatal rifampicin plasma concentrations and data on
neonatal rifampicin pharmacokinetics are completely lacking. Therefore, plasma
concentrations of rifampicin and its main metabolite 25-O-desacetylrifampicin
(DES) were measured in 123 surplus plasma samples from routine vancomycin
monitoring in 21 neonates using reversed-phase HPLC. Rifampicin peak and trough
plasma concentrations were 4.66 +/- 1.47 mg/L and 0.21 +/- 0.20 mg/L,
respectively, after a dose of 8.5 +/- 2.1 (mean +/- SD) mg/kg per day. A
significant linear relationship between rifampicin dose and peak plasma
concentrations was found, but inter-patient variability was high. Pharmacokinetic
parameters of rifampicin were calculated according to a one-compartment open
model with iterative two-stage Bayesian fitting (MW?PHARM 3.60, Mediware, The
Netherlands). First-order elimination constant, volume of distribution corrected
for weight, total body clearance corrected for weight (CL/W), and elimination
half-life were 0.16 +/- 0.06 h(-1), 1.84 +/- 0.59 L/kg, 0.28 +/- 0.11 Lkg(-1) h(
1), and 4.9 +/- 1.7 h, respectively. A high Pearson correlation was found between
CL/W rifampicin and the covariates plasma creatinine and CL/W gentamicin of a
preceding gentamicin treatment course, r = 0.728 (n = 17) and r = 0.837 (n = 12),
respectively. DES was detected in each plasma sample. Therefore, rifampicin seems
to be eliminated by both renal and metabolic pathways in neonates. In 8 study
patients, plasma concentrations of rifampicin and DES were measured again after
two weeks of therapy. CL/W rifampicin was significantly higher (67 +/- 50%). The
authors suggest maintaining the current dose regimen of 10 mg/kg once a day.
Because of the large inter-patient variability in rifampicin plasma
concentrations and CL/W increase during therapy, the authors suggest monitoring
rifampicin peak and trough plasma concentrations to avoid low plasma
concentrations. More research is needed to determine well-founded dosing
guidelines.
PMID- 17038882
TI - False-positive serum tricyclic antidepressant concentrations using fluorescence
polarization immunoassay due to the presence of hydroxyzine and cetirizine.
AB - A recent report indicates that hydroxyzine and its active metabolite cetirizine
interfere with the PENTINA carbamazepine assay. The potential interference of
hydroxyzine and cetirizine with the fluorescence polarization immunoassay (FPIA)
and CEDIA assay of carbamazepine as well as with the fluorescence polarization
immunoassay of tricyclic antidepressants (TCA) was studied. Aliquots of drug-free
serum pools were supplemented with various concentrations of hydroxyzine and
cetirizine representing therapeutic, mild to moderate toxic as well as very toxic
concentrations. Then apparent carbamazepine and TCA concentrations were measured
by immunoassays. Although no interference of hydroxyzine and cetirizine was
observed with carbamazepine assays (FPIA and CEDIA), significant apparent TCA
concentrations were observed when aliquots of drug-free serum were supplemented
with hydroxyzine or cetirizine. Mathematical formula was devised to predict
hydroxyzine and/or cetirizine concentration in serum based on observed apparent
TCA levels. Hydroxyzine and cetirizine also falsely increased total TCA values
when aliquots of serum pool prepared from patients receiving TCA were further
supplemented with these drugs. In conclusion, hydroxyzine and cetirizine do not
interfere with the FPIA and CEDIA carbamazepine assays but interfere with the
measurement of total TCA using the FPIA.
PMID- 17038883
TI - The relationship between P-glycoprotein (PGP) polymorphisms and response to
olanzapine treatment in schizophrenia.
AB - P-glycoprotein (PGP) is a polymorphic efflux transporter located on the blood
brain barrier that potentially affects the penetration of atypical antipsychotics
into the central nervous system. Increased antipsychotic penetration to the
primary site of activity may result in greater symptom improvement or the
occurrence of side effects. This investigation examined the relationship between
three common PGP polymorphisms (C1236T, G2677TA, and C3435T) and response to 6
weeks of open-label olanzapine treatment in patients with schizophrenia.
Individuals with a PGP T allele at any of these polymorphisms would be expected
to have greater antipsychotic penetration through the blood brain barrier, due to
lower PGP activity. Forty-one patients were included in this reanalysis. For
subjects in the 3435T allele carrier group, the plasma olanzapine level alone was
positively associated with percent change in Brief Psychiatric Rating Scale score
(p = 0.02). This relationship was not seen for the 3435CC group (p = 0.583). A
similar trend was observed for negative symptom reduction, olanzapine plasma
concentration, and the 3435T allele (p = 0.06), but this relationship did not
meet statistical significance. There was no relationship between the PGP
genotypes and changes in weight over the course of this 6 week study. The
analysis using C1236T or G2677AT genotypes gave similar results, due to linkage
of these polymorphisms.PGP polymorphisms may affect the penetration of olanzapine
into the central nervous system as seen by a relationship between the 3435T
allele, olanzapine plasma levels, and reduction in the positive symptoms of
schizophrenia. This may stem from greater olanzapine central nervous system
latency due to the presence of the 3435T allele and reduced PGP activity. The PGP
C3435T genotype may help to determine positive symptom reduction from olanzapine
clinically, but these findings should be replicated in a larger sample of
subjects.
PMID- 17038884
TI - AmpliChip CYP450 GeneChip: a new gene chip that allows rapid and accurate CYP2D6
genotyping.
AB - Methods for Cytochrome P450-2D6 (CYP2D6) genotyping are often time-consuming and
laborious, which can restrict their use in pretherapeutic screening programs.
Gene chip technology could overcome this problem. The aim of this study was to
evaluate CYP2D6 genotyping by a new improved gene chip compared to a PCR-RFLP
method. AmpliChip CYP450 GeneChip(R) (AmpliChip) is a microarray hybridization
method for genotyping CYP2D6 and CYP2C19. One hundred fifty-nine DNA samples were
genotyped both by AmpliChip as well as by PCR-RFLP and, where applicable, by a
SNaPshot technique which detects single nucleotide polymorphisms based on the
single base extension principle. In 152 of the 159 samples, CYP2D6 genotypes
determined with the AmpliChip were in accordance with the results of PCR-RFLP.
All seven discrepant samples had gene duplications and were subjected to SNaPshot
analysis. SNaPshot results concurred with those of the AmpliChip for six out of
seven samples. In the one divergent result, DNA sequencing confirmed that the
AmpliChip had assigned the correct genotype. In conclusion, AmpliChip is a highly
reliable method for CYP2D6 genotyping that allows the correct determination of
all relevant CYP2D6 alleles in one single run. It therefore represents a very
efficient and fast method, offering new perspectives for the application of
pharmacogenetics in clinical medicine.
PMID- 17038885
TI - A rapid and inexpensive method for anticipating severe toxicity to fluorouracil
and fluorouracil-based chemotherapy.
AB - Dihydropyrimidine dehydrogenase (DPD) deficiency leads to dramatic overexposure
to fluorouracil (5-FU), resulting in a potentially lethal outcome in patients
treated with standard doses. The aim of this study was to validate, in a routine
clinical setting, a simple and rapid method to determine the DPD status in a
subset of cancer patients, all presenting with life-threatening toxicities
following 5-FU or capecitabine intake. In this study, 80 out of 615 patients
(13%) suffered severe toxicities, including 5 lethal ones (0.8%), during or after
chemotherapy with a fluoropyrimidine drug. Patients with severe toxicities were
treated with 5-FU (76 patients) or capecitabine-containing protocols (4
patients). Simplified uracil to di-hydrouracil (U/UH2) ratio determination in
plasma was retrospectively performed in these 80 patients, as a surrogate marker
of DPD activity. When possible, 5-FU Css determination was performed, and
screenings for the canonical IVS14+1G>A mutation were systematically carried out.
Comparison of the U/UH2 ratios with a reference, non-toxic population, showed
abnormal values suggesting impaired DPD activity in 57 out of the 80 toxic
patients (71%) included in this study, and in 4 out of 5 patients (80%) with a
fatal outcome. Similarly, drug exposures up to 15 times higher than the range
observed in the non-toxic population were also observed. Importantly, no
IVS14+1G>A mutation was found in these patients, including those displaying the
most severe or lethal toxicities. These data warrant systematic detection of DPD
deficient patients prior to fluoropyrimidine administration, including when oral
capecitabine (Xeloda) is scheduled. Finally, the simplified methodology presented
here proved to be a low cost and rapid way to identify routinely patients at risk
of toxicity with 5-FU or capecitabine.
PMID- 17038886
TI - Pitfalls in TDM of antibiotic drugs: analytical and modelling issues.
AB - The quality assurance program of the Dutch KKGT [Association for Quality
Assessment in therapeutic drug monitoring (TDM) and Clinical Toxicology] has been
running for more than 25 years. One of these programs concerns TDM of the
antibiotic drugs gentamicin, tobramycin, amikacin, and vancomycin. We present two
issues encountered in a recent survey. In a case of gentamicin monitoring and
dose-adjustment, a systematic analytical error in some centers led to a dosing
recommendation that differed from that of the organizers. Correction of the
analytical results on the basis of a standard control sample resulted in
concentration differences of more than 20% and different dosing recommendations
in these centers. In a case of vancomycin TDM, the choice of the population model
proved to be critical for dose adjustment. We illustrate this example by
presenting the plasma profiles derived from the different population models used
by the participants.
PMID- 17038887
TI - Identification of a sibutramine-metabolite in patient urine after intake of a
"pure herbal" Chinese slimming product.
PMID- 17038888
TI - Pharmacokinetic characterization of amantadine in human brain tissue.
AB - Amantadine concentrations in human brain tissue were assessed in order to
estimate population pharmacokinetic parameters using the computer program NONMEM.
The elimination constant in brain tissue was determined to be 0.00447 [1/h],
resulting in a t1/2 of 6.5 days for the mean patient in the population
investigated (n = 19). An estimate of 65.5 L was obtained for the apparent volume
of distribution. The elimination half-life of amantadine from brain tissue is
much longer than from blood and is comparable to the previously investigated
neuroleptic drugs haloperidol and levomepromazine.
PMID- 17038889
TI - Therapeutic monitoring of clozapine in Australia: the need for consensus.
AB - In the absence of well-defined guidelines for the monitoring of plasma
concentrations of clozapine, this study examined the practices of seven
laboratories from four states in Australia. Laboratories analyzed 5 freeze-dried
serum samples containing a mixture of clozapine and norclozapine in varying
concentrations and the measurement data were analyzed for accuracy and precision.
Additional information on laboratory practices was obtained through questionnaire
responses. Measurement precision amongst the laboratories was good but there were
significant differences in the accuracy of measurements from one laboratory.
There were differences in the ranges for which assays had been validated and in
suggested therapeutic ranges. These differences could have a significant impact
on the interpretation of measured concentrations and patient care, and emphasize
the need for consensus in this area. Repeat concentration measurements are
recommended in the case of drug concentration measurements that are inconsistent
with clinical observations or previous measurements.
PMID- 17038890
TI - Quantification of Delta9-tetrahydrocannabinol and its major metabolites in
meconium by gas chromatographic-mass spectrometric assay: assay validation and
preliminary results of the "meconium project".
AB - A rapid and simple procedure based on gas chromatography-mass spectrometry (GC
MS) is described for determination of Delta-tetrahydrocannabinol (THC), 11
hydroxy-Delta-tetrahydrocannabinol (THC-OH) and 11-nor-Delta-tetrahydrocannabinol
9-carboxylic acid (THC-COOH) in meconium using Delta-tetrahydrocannabinol (Delta
THC) and deuterated THC-COOH as internal standards. The biological matrix was
subjected to liquid-liquid extraction after enzyme hydrolysis for conjugated
analytes.Chromatography was performed on a fused silica capillary column and
analytes were determined in the selected-ion-monitoring (SIM) mode. The method
was validated in the range 20 to 500 microg/g using 1g of meconium per assay. The
method was applied to the analysis of meconium in a cohort of newborns to assess
eventual fetal exposure to cannabis. Within positive samples, THC-COOH and THC-OH
(range: 33.7 to 182.1 and 20.7 to 493.3 microg/g, respectively) were both present
in the majority of cases with only 1 specimen with THC-OH as the most abundant
metabolite and 2 with THC only.
PMID- 17038891
TI - No influence of 3435C>T ABCB1 (MDR1) gene polymorphism on risk of adult acute
myeloid leukemia and P-glycoprotein expression in blast cells.
AB - Inherited differences in xenobiotic transport and metabolism may play an
important role in the development of adult acute myeloid leukemia (AML) and
response to the chemotherapy. An ATP-binding cassette (ABC) family transporter P
glycoprotein (P-gp or ABCB1), encoded by ABCB1 (MDR1) gene, is involved in the
protection against xenobiotics and multi-drug resistance. The aim of this study
was to investigate the potential involvement of the ABCB1 gene exon 26 3435C>T
single nucleotide polymorphism (SNP) in the genetic susceptibility to AML and
regulation of P-gp expression and activity in AML cells. A total of 180 adult AML
patients and 180 sex-matched controls were genotyped using PCR-RFLP method.
Moreover, in 40 AML patients ABCB1 gene expression was studied by real-time RT
PCR and P-gp expression and activity were assessed by flow cytometry assays. The
prevalence of 3435C>T ABCB1 polymorphism was similar in patient and control
cohorts (P = 0.16). Furthermore, the carriers of different ABCB1 genotypes did
not differ significantly according to ABCB1 gene expression (P = 0.99), P-gp
expression (P = 0.42) and P-gp activity (P = 0.83) in leukemic cells. The authors
conclude that isolated 3435C>T ABCB1 SNP is not a major factor of the genetic
susceptibility to adult AML, and that genotyping of this polymorphism does not
allow predicting P-gp expression or activity in AML cells.
PMID- 17038892
TI - Contextualizing methadone-related deaths: failure to contextualize may be
considered a weapon against public health.
PMID- 17038894
TI - Measuring unbound versus total valproate concentrations for therapeutic drug
monitoring.
PMID- 17038895
TI - Clinical relevance of TDM of SSRIs.
PMID- 17038897
TI - Treatment of hepatitis C virus infection (HCV) after renal transplantation:
implications for HCV-positive dialysis patients awaiting a kidney transplant.
AB - Patient survival is significantly lower in hepatitis C virus (HCV)-positive
compared to HCV-negative dialysis patients. After renal transplantation,
immunosuppressive therapy can result in an increased burden of HCV viremia. Both
patient and graft survivals are lower in HCV-positive compared to matched HCV
negative renal-transplant patients. Therefore, it is important to treat HCV
infection. At present, after renal transplantation, there is no current safe and
efficient therapy. Alpha-interferon (alpha-IFN) does not give a sustained
virological response, and is associated with a high rate of renal failure.
Ribavirin and amantadine monotherapies are associated with a significant
improvement in liver enzymes, but have no impact upon HCV viremia. Ribavirin,
however, may be indicated in cases of HCV-related glomerulopathy because it can
significantly decrease proteinuria. The combined use of alpha-IFN and ribavirin
should only be given to those patients who have developed posttransplant
fibrosing cholestatic hepatitis. Therefore, HCV infection needs to be treated
pretransplant. In dialysis patients, the only recommended therapy, as yet, is
alpha-IFN monotherapy. Pegylated alpha-IFN is under evaluation and ribavirin is
contraindicated because it results in severe hemolytic anemia. Twelve months of
alpha-IFN therapy results in sustained virological clearance in approximately 40%
of patients, regardless of their genotype. HCV RNA, after three months of alpha
IFN therapy, is a predictive factor for a long-term sustained response. Finally,
when HCV-positive dialysis patients with a sustained virological response undergo
successful renal transplantation, very few suffer a virological relapse, thus
emphasizing that these patients were cured.
PMID- 17038898
TI - Antibody and complement mediated injury in transplants following sensitization by
allogeneic blood transfusion.
AB - BACKGROUND: Many patients on the waiting list for transplants are sensitized from
previous blood transfusions, pregnancy, or transplants. We investigated the role
of complement in acute and chronic pathology in hearts transplanted to sensitized
rats. METHODS: Blood was transfused from allogeneic PVG.R8 rats or control
isogeneic PVG.1U rats to C6-sufficient and -deficient PVG.1U rats. Three weeks
later hearts were transplanted from PVG.R8 donors and low-dose cyclosporin A was
initiated. RESULTS: Allogeneic but not isogeneic blood transfusion elicited
strong immunoglobulin (Ig) M, IgG1 and IgG2b alloantibody responses.
Sensitization caused accelerated acute rejection of cardiac allografts by C6
sufficient recipients (4 days). In contrast, allografts functioned over 40 days
in all C6-deficient recipients, but sensitization caused increased interstitial
fibrosis and chronic vasculopathy. Circulating alloantibodies were associated
with deposits of C4d on the vascular endothelium together with pericapillary
accumulation of neutrophils and macrophages in the grafts. In contrast, T cells
accumulated in periarterial lymphatics that did not have C4d deposits.
CONCLUSIONS: Presensitization by allogeneic blood transfusion causes accelerated
acute graft rejection in the presence of the complete complement cascade. In the
absence of C6, macrophages colocalized with deposits of C4d and T cells
accumulated in the periarterial lymphatics.
PMID- 17038899
TI - Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic
rats.
AB - BACKGROUND: Experimental therapeutics for degenerative and traumatic diseases of
the nervous system have been recently enriched with the addition of neural stem
cells (NSCs) as alternatives to fetal tissues for cell replacement.
Neurodegenerative diseases present the additional problem that cell death signals
may interfere with the viability of grafted cells. The adult spinal cord raises
further challenges for NSC differentiation because of lack of intrinsic
developmental potential and the negative outcomes of several prior attempts.
METHOD: NSCs from human fetal spinal cord were grafted into the lumbar cord of
SOD1 G93A rats. The differentiation fate of grafted NSCs and their effects on
motor neuron number, locomotor performance, disease onset, and survival
trends/longevity were assessed. Trophic mechanisms of observed clinical effects
were explored with molecular and cellular methodologies. RESULT: Human NSCs
showed extensive differentiation into neurons that formed synaptic contacts with
host nerve cells and expressed and released glial cell line-derived neurotrophic
factor and brain-derived neurotrophic factor. NSC grafts delayed the onset and
progression of the fulminant motor neuron disease typical of the rat SOD1 G93A
model and extended the lifespan of these animals by more than 10 days, despite
the restricted grafting schedule that was limited to the lumbar protuberance.
CONCLUSION: NSC grafts can survive well in a neurodegenerative environment and
exert powerful clinical effects; at least a portion of these effects may be
related to the ability of these grafts to express and release motor neuron growth
factors delivered to host motor neurons via graft-host connections.
PMID- 17038900
TI - Racial disparities in living kidney donation: is there a lack of willing donors
or an excess of medically unsuitable candidates?
AB - BACKGROUND: Live kidney donation is safe for healthy donors and an effective
treatment for patients with end-stage renal disease. Many potential donors are
referred for live kidney donation, but only a small percentage donate. This study
aims to determine reasons for nondonation and establish if racial differences
exist. METHODS: A retrospective database and chart review of all patients that
were referred for potential live kidney donation from January 1, 2000 to December
31, 2004 was conducted. RESULTS: In all, 30.3% of referred potential live kidney
donors were lost to follow-up. Primary reasons for nondonation (n=1,050) included
unsuitable donor health (43.1%) and recipient-based causes (41.3%). Immunologic
incompatibility accounted for 9.7% of all nondonations. Racial differences
indicated more African Americans had incompatible blood types (P=0.01) or
ineligible recipients (26.7% vs. 14.4%, P<0.01). More non-African Americans
donated (13.2% vs. 4.6%, P<0.01) or were halted because the potential recipient
received another organ (living/cadaveric) (20.0% versus 7.9%, P<0.01).
Nondonation due to overall donor health (including diabetes and hypertension) did
not differ between races, but subanalysis indicated more African American
nondonation was due to high body mass index (P=0.01). CONCLUSIONS: Determining
the reason behind nondonation is a first step towards understanding low rates of
live kidney donation. More African American donor referrals are lost to follow-up
while rates of other reasons were similar among races. This may indicate that
African Americans are not more frequently medically unsuitable, but that the
divergence in rates of live kidney donation is caused by a disparity in
willingness to donate among African Americans.
PMID- 17038901
TI - Kidney transplant outcomes in the indigenous population in the Northern Territory
of Australia.
AB - BACKGROUND: Indigenous Australians develop end-stage renal disease (ESRD) at a
significantly higher rate than nonindigenous Australians. Renal transplantation
is the preferred treatment modality; however, they are underrepresented in the
transplanted population. In addition, despite the morbidity and mortality gains
demonstrated in other patient groups, it is unclear whether such an advantage is
replicated for indigenous Australians. We have sought to identify some of the
factors that lead to poorer outcomes within this group of recipients. METHODS: We
performed a retrospective analysis of a cohort of renal transplant recipients
(indigenous and nonindigenous) from the Northern Territory of Australia. RESULTS:
Indigenous patients waited longer on dialysis, were more sensitized at the time
of transplantation, and the number of human leukocyte antigen mismatches was
greater. Overall renal allograft survival is poorer among indigenous Australians
(HR 4.13, 2.0-8.5, P<0.0001) with the majority of grafts lost due to recipient
death. The most common cause of death was septicemia. Graft loss due to any cause
has not been influenced by the absence of full-time specialist staff at major
treatment centers. Infection rates are greatly increased in indigenous patients
(RR 4.1, 95% CI 3.5-4.7, P<0.0001), in addition to the incidence of rejection (RR
2.5 95% CI 1.8-3.5, P<0.001) and hospitalization (RR 3.9, 95% CI 3.2-4.9,
P<0.0001). There is increased steroid exposure among indigenous recipients.
CONCLUSIONS: Indigenous recipients of cadaveric kidney transplants have worse
outcomes than nonindigenous recipients, mostly due to increased mortality and
morbidity from infective causes.
PMID- 17038902
TI - Portopulmonary hypertension in the early phase following liver transplantation.
AB - BACKGROUND: Portopulmonary hypertension (PPH) is a severe complication of liver
cirrhosis, which poses a high risk for postliver transplantation (LT) mortality.
In most liver transplant centers, severe PPH is viewed as an absolute
contraindication for LT, but recent reports challenge this. The purpose of our
study was to determine the incidence of PPH, its influence on the 30-day
mortality rate following LT and to determine the sensitivity and specificity of
Doppler echocardiography and electrocardiography as noninvasive tools to
determine PPH. METHODS: We studied 74 consecutive patients that underwent LT
between February 2004 and November 2005. Pulmonary arterial pressure and cardiac
index were repeatedly determined during surgery and postoperatively. PPH was
defined as mild (mean pulmonary arterial pressure (MPAP) 25-35 mm Hg), moderate
(MPAP of 35-45 mm Hg) and as severe (MPAP >45 mm Hg). RESULTS: The total
incidence of PPH was 31% (16 mild, 5 moderate, and 2 severe). There was a
tendency towards increased 30-day mortality rate in patients with PPH compared to
controls (22% vs. 12%, P=0.1). However, the two patients with the most severe PPH
survived. The duration of ventilation and total stay at the intensive care unit
did not differ significantly between groups. The positive predictive value of
Doppler echocardiography for PPH was 39% and the negative predictive value 90%.
CONCLUSIONS: Mild pulmonary hypertension is common in patients with liver
failure, whereas moderate and severe hypertension is not. Severe PPH should not
be considered as absolute contraindication for LT.
PMID- 17038903
TI - The current practice of live donor nephrectomy in Europe.
AB - BACKGROUND: The increasing number of live kidney donors in the last decade has
stimulated interest in the surgical technique of donor nephrectomy. In this
study, we evaluated the current status of the surgical approach in European
transplant centers. METHODS: A questionnaire was sent to 131 centers in 12
European countries. Questions included the number of donors, the technique used,
and the inclusion and exclusion criteria for a technique. RESULTS: Ninety-two
replies (70%) were included. In the responding centers, approximately 1450 live
donor nephrectomies were performed in 2004 (more than 80% of all live kidney
donations in these countries). The number of living donors ranged from 0 to 95
per center. Nineteen institutions (21%) removed kidneys using endoscopic
techniques only. Twenty-two centers (24%) performed both open and laparoscopic
donor nephrectomy. Vessel length, difficult anatomy and right-sided donor
nephrectomy were common reasons to choose an open technique. Twelve centers had
performed laparoscopic donor nephrectomy but quit their program for various
reasons. In 51 centers (55%), only open donor nephrectomy was carried out. Lack
of evidence that endoscopic techniques provide better results was the main reason
for these centers to stick to an open approach. Incisional hernias occurred after
all types of open surgery in up to 30% of the donors per center. Twenty-nine
clinics still carry out the classic flank incision. CONCLUSION: The surgical
technique of live donor nephrectomy varies greatly between transplant centers in
European countries. To define the optimal surgical approach a European
registration of donor nephrectomies would be helpful.
PMID- 17038904
TI - Developing a prognostic model for 90-day mortality after liver transplantation
based on pretransplant recipient factors.
AB - BACKGROUND: Current statistical prognostic models for mortality after liver
transplantation do not have good discriminatory ability. Furthermore, the
methodology used to develop these models is often flawed. The objective of this
paper is to develop a prognostic model for 90-day mortality after liver
transplantation based on pretransplant recipient factors, employing a rigorous
model development method. METHODS: We used data on 4,829 patient that were
prospectively collected for the UK & Ireland Liver Transplant Audit. Switching
regression was employed to impute missing values combined with a bootstrapping
approach for variable selection. RESULTS: In all, 452 patients (9.4%) died within
90 days of their transplantation. The final prognostic model was well calibrated
and discriminated moderately well between patients who did and who did not die (c
statistic 0.65, 95% CI [0.63, 0.68]). Although discrimination was not excellent
overall, the results showed that those patients with a "low" chance of dying
within 90 days of their transplant and those with a "high" chance of dying could
be differentiated from patients with a "intermediate" chance. CONCLUSIONS: Our
model can provide transplant candidates with predictions of their early
posttransplantation prospects before any donor information is known, which is
essential information for patients with end-stage liver disease for whom liver
transplantation is a treatment option.
PMID- 17038905
TI - Sirolimus interferes with iron homeostasis in renal transplant recipients.
AB - BACKGROUND: Sirolimus is an immunosuppressive drug whose use is frequently
associated with anemia. A pathogenic link between sirolimus-induced anemia and
the appearance of an inflammatory state was recently suggested. Because
inflammation-related anemia is characterized by a functional iron deficiency, we
investigated whether sirolimus may influence iron homeostasis and serum levels of
hepcidin, a key mediator of inflammation-related anemia. METHODS: To this
purpose, 42 consecutive transplanted patients with biopsy-proven chronic
allograft nephropathy were randomized (2:1 ratio) to receive either a 40%
cyclosporine reduction (group A, 14 patients) or immediate cyclosporine
withdrawal and sirolimus introduction (group B, 28 patients). Hemoglobin levels
and iron status were evaluated 6 months before and after randomization. RESULTS:
The two groups had similar hemoglobin levels and iron status at baseline. We did
not observe any significant change in hemoglobin and iron status in group A
patients after randomization. On the contrary, we observed a significant
reduction of hemoglobin without any change of red blood cell count after
sirolimus introduction, with a significant reduction of mean corpuscular volume
and mean corpuscular hemoglobin. Serum iron and transferrin saturation (TSAT)
levels were markedly reduced after the switch, while ferritin serum
concentrations remained stable. Although sirolimus-induced anemia was recently
suggested to resemble inflammation-related anemia, hepcidin serum levels were
similar in the two groups after randomization. None of group A and eight of group
B patients presented a TSAT <20 and were given iron supplementation after
randomization, in all of them oral iron therapy did not influence either
hemoglobin or serum iron levels. CONCLUSION: We demonstrated that sirolimus
induced anemia is independent of the drug antiproliferative effect and does not
present the features of inflammation-related anemia. This event may be due to the
direct influence of sirolimus on iron homeostasis.
PMID- 17038906
TI - Unrelated versus related allogeneic stem cell transplantation after reduced
intensity conditioning.
AB - BACKGROUND: The use of reduced intensity conditioning (RIC) regimens in
allogeneic hematopoietic stem cell transplantation (HSCT) has increased over the
past five years. PATIENTS: In this study, involving 137 patients, we compared the
outcome after RIC in patients receiving grafts from matched unrelated donors
(MUD; n=74) and sibling donors (n=63). The MUD and sibling groups were comparable
regarding diagnosis, including solid tumors and hematological malignancies, and
conditioning regimens. RESULTS: Engraftment was successful in most patients
(88%), with no significant difference between MUD and sibling transplants.
Cytomegalovirus (CMV) infection was more common in the MUD group (65%) than in
the sibling group (46%) (P=0.04). No difference in severe acute graft-versus-host
disease (GVHD) was found between the groups. However, the incidence of chronic
GVHD was higher after sibling transplants. This was probably due to higher donor
age in this group, since this was the only significant risk factor for chronic
GVHD in multivariate analysis. The incidence of transplant related mortality
(TRM) was significantly higher after MUD transplantation (40%) than after sibling
transplantation (16%) (P<0.01). Because relapse/disease progression was more
common after sibling transplantation, there was no significant difference in
overall survival between the two groups. CONCLUSION: Using unrelated donors after
RIC is feasible, but it resulted in more CMV infection and increased transplant
related mortality. Survival was comparable to that of sibling transplants.
PMID- 17038907
TI - Impaired arterial compliance and aerobic endurance in kidney transplant
recipients.
AB - BACKGROUND: Cardiovascular disease is the leading cause of morbidity and
mortality in kidney transplant recipients (KTR). Two risk factors for
cardiovascular disease that have not been examined in this population are
arterial compliance and aerobic capacity. The primary objective was to determine
small and large artery compliance and aerobic endurance in KTR. A secondary
objective was to explore the relationship between aging and arterial compliance
and aerobic endurance in KTR. METHODS: Sixty-two clinically stable KTR were
recruited from the University of Alberta Renal Transplant Clinic. Small and large
artery compliance was assessed using computerized arterial pulse waveform
analysis. Aerobic endurance was determined using the six-minute walk test. Age
matched normative data from healthy individuals was used for comparison. RESULTS:
Small arterial compliance was lower in KTR (5.5+/-3 ml/mm Hg x 100) compared to
age-matched healthy individuals' predicted values (7.9+/-0.9 ml/mm Hg x 100,
P<0.0001). No difference was found for large artery compliance between KTR
(16.0+/-6.6 ml/mm Hg x 10) and age-matched healthy predicted values (15.2+/-1.3
ml/mm Hg x 10, P=0.5). Small and large artery compliance were 35% (P=0.026) and
36% (P=0.005) higher in younger (<51 years) versus older (>51 years) KTR,
respectively. The six-minute walk distance was 28% lower in KTR (495+/-92 m)
compared to healthy age-predicted values (692+/-56 m P<0.0001). CONCLUSIONS:
Compromised arterial compliance and poor aerobic endurance may partially explain
the high incidence of cardiovascular disease in KTR. Interventions demonstrated
to improve these parameters may afford substantial clinical benefit in this
population.
PMID- 17038908
TI - A comparison of the effects of C2-cyclosporine and C0-tacrolimus on renal
function and cardiovascular risk factors in kidney transplant recipients.
AB - BACKGROUND: There are few data directly comparing the effects of two-hour
postingestion monitored cyclosporine (C2-CsA) vs. trough-monitored tacrolimus (C0
Tac) on renal function and cardiovascular risk factors. METHODS: We studied 378
(202 C2-CsA vs. 176 C0-Tac) incident kidney transplant recipients in Toronto,
Canada, from August 1, 2000 and December 31, 2003. Outcomes included changes in
estimated glomerular filtration rate (eGFR at 1 and 6 months by modification of
diet in renal disease four-variable equation), mean arterial pressure (MAP),
total cholesterol (TC), and new-onset diabetes mellitus (NODM) at six months
posttransplant. The independent effect of treatment/monitoring strategies on
continuous outcomes and time-to-NODM was modeled using linear and Cox regression,
respectively. RESULTS: Mean eGFR was 59.5 vs. 62.9 ml/min at one month and 50.6
vs. 61.2 ml/min at six months for C2-CsA vs. C0-Tac, respectively. Multiple
linear regression revealed the slope of eGFR to be 0.93 ml/min/month lower in C2
CsA patients. This was equivalent to an adjusted average eGFR difference of 4.64
ml/min between months one and six posttransplant. There was no significant
difference in average MAP and TC. In a stepwise multivariable Cox model and a
propensity score analysis, there was no significant association between the type
of treatment/monitoring strategy and time-to-NODM. CONCLUSIONS: There was a
greater decline in eGFR for patients on C2-CsA (vs. C0-Tac) between one and six
months posttransplant. However, MAP, TC, and the risk of NODM were comparable in
both treatment/monitoring groups. The long-term impact of short-term reductions
in eGFR as a function of the type of treatment/monitoring strategy requires
further study.
PMID- 17038909
TI - Curcumin has potent liver preservation properties in an isolated perfusion model.
AB - BACKGROUND: Curcumin has profound antioxidant and anti-inflammatory properties.
This research assessed the effect of curcumin on liver preservation. METHODS:
Sprague-Dawley rat livers were flushed with different preservation solutions
[Euro-Collins solution (EC), phosphate buffer saline (PBS), University of
Wisconsin solution (UW)] with or without curcumin (25-200 microM) and stored at 4
degrees C for 24-48 hours. Livers were then perfused for 120 minutes via the
portal vein with oxygenated Krebs-Henseleit bicarbonate buffer solution at a
pressure of 18 cm H2O in a perfusion apparatus. The livers in the normal (NL)
group were flushed with EC, PBS, or UW, then immediately perfused (zero
preservation time). RESULTS: We found that curcumin at 100 microM concentration
had the optimal preservation characteristics. Portal flow rates and bile
production were significantly higher and liver enzymes (alanine aminotransferase,
aspartate aminotransferase, and lactate dehydrogenase) were significantly lower
in the EC+C livers and PBS+C livers than in the EC or PBS with optimum
concentration of 100 microM of curcumin. Comparing UW+C vs. UW livers, at 24
hours there was no difference in these parameters; however, at 36 hours and 48
hours, portal flow rates and bile production were significantly higher in UW+C
livers. CONCLUSIONS: We found that curcumin has inherent organ preservation
quality as it enhanced liver preservation in PBS. In addition, curcumin enhanced
the preservation quality of EC and UW solutions, thereby extending the
preservation time while maintaining the organ quality.
PMID- 17038911
TI - Neonatal porcine islets exhibit natural resistance to hypoxia-induced apoptosis.
AB - BACKGROUND: Despite the success of the Edmonton protocol for human islet
transplantation, an alternate source of islet tissue must be developed if beta
cell replacement therapy is to see widespread application. Neonatal porcine
islets (NPI) represent one potential source of tissue. When human or rodent
islets are transplanted, the majority of cells undergo hypoxia-induce apoptosis
soon after the grafts are placed in the recipient. In the present study, we
investigated whether NPI were similarly sensitive to hypoxia. METHODS: NPI were
exposed to hypoxia and hypoxia/reoxygenation using an in vitro hypoxic chamber.
Afterwards, viability, frequency of apoptosis, and beta-cell function were
evaluated. NPI and adult porcine islets were transplanted into chemically
diabetic, immunodeficient mice and graft apoptosis was assessed 24 hours and
seven days posttransplant. RESULTS: NPI demonstrated a remarkable capacity to
resist apoptosis and maintain insulin secretion despite severe stresses such as
hypoxia/reoxygenation. One day after transplantation, NPI grafts showed limited
apoptosis, confined to rare strongly insulin positive cells. In contrast, adult
porcine islet grafts underwent widespread apoptosis. Western blotting revealed
that NPI express high levels of at least one potent endogenous antiapoptotic
protein (XIAP). CONCLUSIONS: The majority of cells within transplanted human
islets undergo apoptosis soon after portal infusion. In contrast, NPI have the
capacity to resist this early posttransplant apoptosis, with likely reduced
antigen release and diminished immune stimulation. NPI appear to contain a
population of insulin-low to insulin-negative pre-beta-cells, which are resistant
to hypoxia-induced apoptosis and still capable of differentiating into mature
beta-cells.
PMID- 17038910
TI - Induction of carbon monoxide in donor animals prior to organ procurement reduces
graft immunogenicity and inhibits chronic allograft dysfunction.
AB - BACKGROUND: Nonspecific inflammatory damages occurring prior to organ
transplantation reduce long-term graft survival. Here, we tested the beneficial
effects of carbon monoxide (CO) induction by methylene chloride (MC). METHODS:
Fischer-344 (F-344 Rat) or Dark Agouti (DA Rat) donor animals were either treated
with MC four hours prior to organ removal or remained untreated. Kidneys were
transplanted into Lewis (LEW) recipients. The low responder strain combination (F
344-->LEW) was studied for long-term graft changes. Dendritic cells (DCs)
migration and early changes were followed in additional groups of a high
responding donor/recipient strain combination (DA-->LEW). Native kidneys of
uninephrectomized, age-matched normal animals served as controls. RESULTS:
Following MC application COHb peaked within two hours in donor animals. Renal
function and morphology improved significantly in renal allografts of CO induced
donor animals and were comparable to native controls long-term (24 wks). Early
after transplantation (24 hr) donor-derived DCs, CD4+ T-cells and alloreactive T
cells were significantly reduced following the engraftment of organs from treated
donors. In addition, a trend towards a Th1/Th2 shift and a significant intragraft
reduction of CD3 mRNA expression was observed. CONCLUSION: Donor treatment for
the induction of CO reduced graft immunogenicity and inhibited chronic allograft
nephropathy.
PMID- 17038912
TI - Requirement of CD28 signaling in homeostasis/survival of TGF-beta converted
CD4+CD25+ Tregs from thymic CD4+CD25- single positive T cells.
AB - BACKGROUND: The thymus is a major organ that generates "natural" CD4+CD25+ T
regulatory cells (Tregs). However, the detailed pathway(s) by which Tregs are
developed remain a mystery. CD28-/- mice have profound decrease in Tregs, but the
underlying molecular events remain largely undefined. METHODS: CD4+CD25+
thymocytes from wildtype and CD28-/- mice were cultured with T-cell receptor
(TCR) and transforming growth factor (TGF)-beta stimulation to generate CD25+
Tregs and their phenotype and function were studied in vitro and in vivo.
RESULTS: TGF-beta induced Foxp3 expression in thymic CD4+CD25+ cells and
converted them to CD25+ Tregs. The converted Tregs expressed high levels of CD25,
whereas the non-suppressive CD4+ T cells from the control cultures expressed
CD25(low). CD28-/- thymic CD4+CD25+ cells showed transit lower levels of Foxp3
upon TCR and TGF-beta stimulation early in culture, but the defect in Foxp3
expression was restored to normal levels after 60-72 hr. Consequently, TGF-beta
converted CD28-/- CD25+ cells to CD25+ Tregs that were indistinguishable from
those of the wildtype mice. However, the total number of TGF-beta converted CD28
/- Tregs was significantly lower than that of wildtype mice. In vivo, TGF-beta
converted CD28-/- CD25+ Tregs were less viable than those from the wildtype mice.
Importantly, TGF-beta induced alloantigen specific CD4+CD25+ Tregs from thymic
CD25-SP cells which also required CD28 to maintain their survival. CONCLUSIONS:
TGF-beta and TCR co-stimulation converts thymic CD4+CD25+ T cells into CD4+CD25+
Tregs by inducing Foxp3, and the contribution of CD28 stimulation to this process
is mainly through maintaining survival of the induced Tregs.
PMID- 17038913
TI - Rabbit antithymocyte globulin inhibits monocyte-derived dendritic cells
maturation in vitro and polarizes monocyte-derived dendritic cells towards
tolerogenic dendritic cells expressing indoleamine 2,3-dioxygenase.
AB - BACKGROUND: Rabbit antithymocyte globulin (rATG) is a polyclonal mixture of
immunoglobulin (Ig) G. It is used to prevent graft rejection and also graft
versus host disease after transplantation. Its effect on lymphocyte function has
been widely studied. Dendritic cells are central actors of the immune system. As
antigen presenting cells, they are able to initiate, stimulate, and modulate
immune responses. METHODS: In this study, we investigated rATG effects on in
vitro differentiation and maturation of monocyte-derived dendritic cells (Mo
DCs). RESULTS: rATG inhibited maturation of immature Mo-DCs and allowed the
generation of dendritic cells expressing ILT-3, CD123, CCR6 but not CCR7 and
producing Indoleamine 2,3-dioxygenase mRNA as well as interferon-alpha.
CONCLUSION: rATG polarizes in vitro Mo-DCs towards tolerogenic dendritic cells.
PMID- 17038914
TI - Direct and rapid modification of a porcine xenoantigen gene (GGTA1).
AB - The ability to modify animal genomes rapidly at a specific locus would be
valuable both for research purposes and in the development of animals suitable
for xenotransplantation. In a proof-of-concept study, we used a unique, homology
dependent strand transferase protein called drosophila recombination-associated
protein (DRAP) and DNA oligonucleotides to modify the porcine gene encoding alpha
1,3 galactosyl transferase (GGTA1). This gene is responsible for generating
xenotransplantation antigens resulting in hyperacute rejection. Pronuclear
injection of DRAP and mutant oligonucleotides yielded piglets with heritable,
modified alleles of GGTA1 in a direct, rapid and efficient manner. Cells derived
from these piglets had markedly reduced alpha 1,3 galactosyl sugar epitopes. The
simplicity of this method should permit rapid sequential or simultaneous
modification of the various genes encoding or producing antigens that impose
limits on xenotransplantation as they are discovered.
PMID- 17038915
TI - A prospective survey of human herpesvirus-6 primary infection in solid organ
transplant recipients.
AB - Human herpesvirus 6 (HHV-6) infection is potentially life-threatening to
immunosuppressed patients. There is a lack of information regarding the risk and
the clinical manifestations of primary HHV-6 infection in solid-organ transplant
recipients. We prospectively evaluated patients undergoing solid organ
transplantation with negative immunoglobulin (Ig) G antibodies against HHV-6 by
means of HHV-6 quantitative polymerase chain reaction. Among 193 recipients,
seven were HHV-6 seronegative (prevalence 3.6%). We detected a positive HHV-6
viral load in only one patient, and four patients seroconverted after one year
posttransplantation. The patient with a positive HHV-6 viral load developed
cholestatic hepatitis without fever and did not experience severe end-organ
disease. In conclusion, our findings show a low incidence of symptomatic primary
HHV-6 infection among seronegative solid-organ transplant recipients.
PMID- 17038916
TI - Human islet isolation outcomes from pancreata preserved with Histidine-Tryptophan
Ketoglutarate versus University of Wisconsin solution.
AB - This study was designed to compare Histadine-Tryptophan-Ketogluterate (HTK) with
University of Wisconsin (UW) solution. Pancreata from extended criteria donors
were flushed and transported with HTK (n=41) or UW (n=45). Isolation outcomes
were determined by islet yields, viability and in vitro and in vivo function.
Final yields were similar between two groups (HTK: 383,085 vs. UW: 328,514 EIN,
P=0.14). In the HTK group, 63.4% (26/41) of isolations resulted in a yield of
over 300,000, and in the UW group this was achieved in 46.7% (21/45; P=0.12).
Viability results were similar (HTK: 82.9 vs. UW: 82.7%, P=0.93). Stimulation
index in the HTK and UW groups were comparable (5.28 vs. 4.91, P=0.62). Ten out
of 41 islet preparations in HTK and 4 of 45 in UW group were suitable for
clinical transplantation (P=0.05). Our study shows HTK is equivalent to UW
solution in the preservation of pancreata for islet isolation.
PMID- 17038917
TI - BK viral genotype identification of a renal donor and their recipient pair.
PMID- 17038918
TI - Hypercalcemia related to immune reconstitution in organ transplant recipients
with granulomatous opportunistic infections.
PMID- 17038919
TI - The future challenge in the MELD era: how to match extended-use donors and sick
recipients.
PMID- 17038920
TI - Late humoral rejection in a compliant ABO-compatible liver transplant recipient.
PMID- 17038921
TI - The treatment of acute osteomyelitis by drainage and rest. 1927.
PMID- 17038923
TI - An obscure affection of the hip joint. 1910.
PMID- 17038924
TI - On a particular form of pseudo-coxalgia associated with a characteristic
deformity of the upper end of the femur. 1910.
PMID- 17038925
TI - Concerning arthritis deformans juvenilis. 1910.
PMID- 17038928
TI - Temporomandibular joint cyst presenting as trigeminal neuropathy and middle fossa
mass: case report.
AB - OBJECTIVE: We describe the case of a temporomandibular joint cyst eroding into
the middle fossa, initially causing compression of the trigeminal nerve and
trigeminal neuropathy, and ultimately causing destruction of the second division
of the nerve with facial numbness. CLINICAL PRESENTATION: A 50-year-old woman
with rheumatoid arthritis on prednisone developed right-sided, initially
lancinating facial pain that ultimately became dull in nature in the maxillary
division of the trigeminal nerve. This change in pain was associated with the
development of numbness in the same distribution. The facial pain gradually
resolved, but the facial numbness persisted. Imaging revealed a heterogeneously
enhancing mass in the middle fossa lateral to Meckel's cave. INTERVENTION: During
surgery, the dura was elevated, and a smooth, firm lesion with several thinly
encapsulated, cystic areas containing viscous, white fluid was identified. The
mass had eroded through the floor of the middle cranial fossa. The thick, fibrous
capsule was freed from the bone edges and was sectioned sharply extracranially.
Pathological evaluation was consistent with a cyst originating from the
temporomandibular joint. CONCLUSION: Extracranial mass lesions involving the
middle fossa structures are uncommon and typically arise from the parotid gland.
This case represents the first example of a middle fossa mass originating from an
abnormal temporomandibular joint and a unique cause of trigeminal neuropathy.
After excision, there has been no recurrence after 2 years of follow-up.
PMID- 17038929
TI - Solitary fibrous tumor arising from Cranial Nerve VI in the prepontine cistern:
case report and review of a tumor subpopulation mimicking schwannoma.
AB - OBJECTIVE: The authors present a report of a solitary fibrous tumor (SFT) arising
from the intradural component of the VIth cranial nerve as it travels through the
prepontine cistern. SFTs of the central nervous system are extremely rare
entities that clinically masquerade as dural-based lesions, such as meningiomas
or hemangiopericytomas. Because of their infrequency and clinical similarity to
other central nervous system (CNS) lesions, diagnosis is largely dependent on
pathological features. In this study, the authors define a subpopulation of SFTs
that seem to arise directly from nerve, rather than meninges, and clinically
mimic the appearance of a schwannoma. CLINICAL PRESENTATION: The patient was a 29
year-old woman with a several-month history of progressive right arm and leg
numbness and mild hemiparesis, with the development of diplopia 2 weeks before
admission. Outside imaging revealed a 3.9-cm mass in the prepontine cistern with
extension into Meckel's cave and the cavernous sinus, resulting in significant
brainstem compression. INTERVENTION: The patient underwent preoperative
angiography with embolization of feeding vessels off of the left
meningohypophyseal trunk. The patient was then taken to the operating room by a
combined neurosurgical and ear, nose, and throat team, where the patient
underwent a retrolabyrinthine/subtemporal craniotomy for tumor resection. During
resection of the prepontine component, the tumor was identified as originating
from the left Cranial Nerve VI as it traversed through the prepontine cistern.
Resection of the tumor component involving the cavernous sinus and Meckel's cave
was deferred for follow-up treatment with intensity-modulated radiation therapy.
Pathological examination revealed tissue consistent with the diagnosis of SFT.
CONCLUSION: SFTs involving the CNS are rare entities that are almost always
diagnosed after tissue is obtained because of their clinical and radiographic
similarity to meningiomas. This patient had an SFT masquerading as a VIth cranial
nerve schwannoma. Although the natural history of SFTs in the CNS is not
completely understood, correct diagnosis is important, given the rate of
recurrence found in the more common pleural-based SFT and examples of CNS SFTs
with malignant features.
PMID- 17038930
TI - Utility of preoperative magnetic resonance imaging myelography for identifying
dural defects in patients with spinal extradural arachnoid cysts: case report.
AB - OBJECTIVE: Preoperative magnetic resonance imaging (MRI) myelography scans
demonstrated a dural defect in a 50-year-old man with an epidural arachnoid cyst
who had a 29-year history of untreated weakness and numbness both lower limbs.
METHODS: MRI scans showed a dorsal intraspinal extradural cystic lesion at the
level from Th11 to L1. Although preoperative cine-MRI scans failed to display the
dural defect, an MRI myelography scan showed cerebrospinal fluid in the
subarachnoid space containing a cyst. RESULTS: The site of shunting between the
subarachnoid space and the cyst was visualized as a pulsating flow void to the
right of Th12. We removed the cyst wall and closed the dural defect via
laminectomy. CONCLUSION: Because the preoperative MRI myelography scan correctly
identified the existence and location of the dural defect, we conclude that MRI
myelography is helpful for detecting dural defects in patients with epidural
arachnoid cysts.
PMID- 17038931
TI - Intradural spinal Wilm's tumor metastasis: case report.
AB - OBJECTIVE: Wilm's tumor metastasis to the central nervous system (especially the
spine) is rare. We present a case of a lumbosacral intradural drop metastasis in
a male child with a remote history of intracerebral Wilm's tumor metastases.
CLINICAL PRESENTATION: A 7-year-old boy with known metastatic Wilm's tumor was
discovered to have left frontal and parietal metastases. He subsequently
underwent craniotomy and gross total resections of those lesions. Four years
later, he developed low back pain and lower extremity weakness and was found to
have an intradural lumbosacral lesion without intracranial recurrence.
INTERVENTION: The patient underwent lumbar laminectomy for resection of the
intradural lesion. The tumor was found to be in the subarachnoid space and
displaced the nerve roots of the cauda equina to the periphery of the thecal sac.
The nerve roots were matted and encased within tumor tissue, thereby limiting the
surgery to biopsy only. Postoperatively, the patient received radiation to the
lesion. Unfortunately, follow-up imaging 4 months later revealed little tumor
regression, and the patient's neurological condition did not improve
significantly. CONCLUSION: Spinal intradural Wilm's tumor metastases are rare.
This is the only reported case in the literature of a probable drop metastasis
from an intracerebral source. Although the optimal treatment for intra- or
extradural Wilm's tumor spine metastases is not known, our patient did not make
significant neurological improvement with radiation therapy.
PMID- 17038936
TI - Psychosurgery: avoiding an ethical redux while advancing a therapeutic future.
PMID- 17038937
TI - Education and neuromodulation for psychiatric disorders: a perspective for
practitioners.
PMID- 17038938
TI - Surgery of the mind and mood: a mosaic of issues in time and evolution.
AB - The prevalence and economic burden of neuropsychiatric disease are enormous. The
surgical treatment of these psychiatric disorders, although potentially valuable,
remains one of the most controversial subjects in medicine, as its concept and
potential reality raises thorny issues of moral, ethical, and socioeconomic
consequence. This article traces the roots of concept and surgical efforts in
this turbulent area from prehistory to the 21st century. The details of the late
19th and 20th century evolution of approaches to the problem of intractable
psychiatric diseases with scrutiny of the persona and contributions of the key
individuals Gottlieb Burckhardt, John Fulton, Egas Moniz, Walter Freeman, James
Watts, and William Scoville are presented as a foundation for the later, more
logically refined approaches of Lars Leksell, Peter Lindstrom, Geoffrey Knight,
Jean Talaraich, and Desmond Kelly. These refinements, characterized by
progressive minimalism and founded on a better comprehension of underlying
pathways of normal function and disease states, have been further explored with
recent advances in imaging, which have allowed the emergence of less invasive and
technology driven non-ablative surgical directives toward these problematical
disorders of mind and mood. The application of therapies based on imaging
comprehension of pathway and relay abnormalities, along with explorations of the
notion of surgical minimalism, promise to serve as an impetus for revival of an
active surgical effort in this key global health and socioeconomic problem.
Eventual coupling of cellular and molecular biology and nanotechnology with
surgical enterprise is on the horizon.
PMID- 17038939
TI - Synthetic nerve guide implants in humans: a comprehensive survey.
AB - OBJECTIVE: Lesions of the peripheral nervous system result in the loss of sensory
and motor function and may in addition be accompanied by severe neuropathic
syndromes originating from aberrant axonal regrowth. The transplantation of
autologous nerve grafts represents the current "gold standard" during
reconstructive surgery, despite obvious side effects. Depending on the demands of
the lesion site, various donor nerves may be used for grafting (e.g., the sural,
saphenous), sacrificing native functions in their target areas. Recently, several
synthetic nerve guide implants have been introduced and approved for clinical use
to replace autologous transplants. This alternative therapy is based on
pioneering studies with experimental nerve guides. METHODS: We present a
comprehensive review of all published human studies involving synthetic nerve
guides. RESULTS: Data from some 300 patients suggest that for short nerve defects
of a few centimeters, resorbable implants provide promising results, whereas a
number of late compression syndromes have been documented for nonresorbable
implants. CONCLUSIONS: To treat longer defects, further implant development is
needed, a goal that could be achieved, for example, by more closely imitating the
intact nerve architecture and regulatory cell-cell interactions.
PMID- 17038940
TI - The neurosurgical workforce in North America: a critical review of gender issues.
AB - OBJECTIVE: The role of women in Western society has changed dramatically in the
past several decades. Despite this, many gender disparities still exist for
professionals in the health care sector. In neurosurgery, a disproportionately
small percentage of the workforce in the United States and Canada is female.
These figures are lower than most reported in other medical specialties. This
review critically examines factors that may be influencing women's ability to
advance in demanding subspecialties such as neurosurgery. METHODS: The literature
on women in medicine, and surgery in particular, were reviewed to identify
different issues facing women currently in practice in neurosurgery. In addition,
the concerns of prospective trainees were examined. RESULTS: There remain many
challenges for women entering neurosurgery, including unique lifestyle concerns,
limited mentorship, out-dated career programs, and deep-seeded societal beliefs.
Discrimination and harassment are also contributing factors. CONCLUSION: If
neurosurgery is to continue to progress as a subspecialty, the issue of gender
inequality needs to be scrutinized more closely. Innovative programs must be
developed to meet the needs of current female faculty members and to ensure
attracting the brightest individuals of both genders into a career in
neurosurgery.
PMID- 17038941
TI - Self-assessment in neurological surgery: the SANS wired white paper.
AB - OBJECTIVE: Periodic self-assessment is an important component of postgraduate
medical education and certification. The Self-assessment in Neurological Surgery
(SANS) examination has a history of usefulness for neurosurgical written and oral
board examination preparation. The SANS Wired test represents a recreation of the
original SANS test using an Internet-based platform. Advanced functionality and
contemporary content have been added to meet the increasing requirements for
demonstration of lifelong learning and self-assessment as part of the Maintenance
of Certification (MOC) process. METHODS: A needs assessment was performed before
the development of SANS Wired. Postexamination surveys for users obtaining
continuing medical education credit were analyzed for user satisfaction with the
platform and content. Test-item performance metrics were analyzed based on first
attempt responses. The economic value of SANS Wired as a component of the
mandatory MOC process was evaluated. RESULTS: The needs assessment identified a
deficiency of available content and mechanisms for neurosurgery-specific self
assessment. As of October 15, 2005, a total of 588 individuals had subscribed to
SANS Wired (28 institutional licenses accounted for 229 users). Eighty-eight post
test surveys were analyzed for user satisfaction. Ninety-four percent of
responses indicated that learning objectives had been met. Initial performance
metrics show an average point-biserial discrimination index of +0.18 for all test
items. CONCLUSION: The SANS Wired system seems to be an effective platform for
neurosurgical self-assessment and is acceptable to users. The system satisfies,
in part, two of the four required components of MOC, namely, periodic self
assessment and demonstration of cognitive expertise. It is endorsed by the
American Board of Neurological Surgeons for MOC.
PMID- 17038942
TI - Dynamics of intraventricular hemorrhage in patients with spontaneous
intracerebral hemorrhage: risk factors, clinical impact, and effect of hemostatic
therapy with recombinant activated factor VII.
AB - OBJECTIVE: To evaluate predictors of intraventricular hemorrhage (IVH) and IVH
growth, impact of IVH growth on outcome, and impact of recombinant activated
factor VII (rFVIIa) in patients with intracerebral hemorrhage (ICH). METHODS: We
analyzed 374 patients out of 399 who were randomized to rFVIIa (40, 80, or 160
mug/kg) or placebo for ICH (diagnosed within 3 h of symptoms). Risk factors for
IVH growth (>2 ml increase in IVH volume at 24 h), and death or severe disability
(modified Rankin scale score 4-6) at 3 months were identified (logistic
regression). RESULTS: IVH was present in 38% (n = 141) of patients at baseline
and 45% (n = 169) by 24 hours. IVH growth, by 24 hours, occurred in 17 and 10% of
placebo- and rFVIIa-treated patients, respectively (P = 0.037). Risk factors for
IVH growth included baseline mean arterial pressure greater than 120 mmHg, larger
baseline ICH volume, IVH present at baseline, shorter time from symptom onset to
baseline computed tomographic scan, and treatment (rFVIIa versus placebo) (all, P
< or = 0.037). Predictors of death or severe disability included older age, lower
baseline Glasgow Coma Score, larger baseline ICH volume, IVH growth greater than
2 ml, IVH present at baseline or 24 hours, and treatment (rFVIIa versus placebo)
(all, P < or = 0.0405). CONCLUSION: Presence of IVH at any time and early IVH
growth worsen clinical outcome and increase mortality. Elevated mean arterial
pressure at baseline may be a modifiable risk factor for IVH growth. Beneficial
effects of rFVIIa on ICH outcome may be mediated, at least in part, by reducing
IVH growth.
PMID- 17038943
TI - Higher hemoglobin is associated with less cerebral infarction, poor outcome, and
death after subarachnoid hemorrhage.
AB - OBJECTIVE: Higher-goal hemoglobin (hgb) and more packed red blood cell
transfusions lead to worse outcomes in general critical care patients. There are
few data on hgb, transfusion, and outcomes after aneurysmal subarachnoid
hemorrhage (SAH). METHODS: We reviewed the daily hgb levels of 103 patients with
aneurysmal SAH. Cerebral infarction was diagnosed by computed tomographic scan.
We corrected for Hunt and Hess grade, age, and angiographic vasospasm in
multivariate models. RESULTS: Of 103 patients, the mean age was 55.3 +/- 14.5
years, 63% were women, and 29% were Hunt and Hess Grades 4 and 5; hgb values
steadily declined from 12.6 +/- 1.7 g/dl the day of SAH to 10.4 +/- 1.2 g/dl by
Day 14. Patients who died had lower hgb than survivors on Days 0, 1, 2, 4, 6, 10,
11, and 12 (P < or = 0.05). Higher mean hgb was associated with reduced odds of
poor outcome (odds ratio, 0.57 per g/dl; 95% confidence interval [CI], 0.38-0.87;
P = 0.008) after correcting for Hunt and Hess grade, age, and vasospasm; results
for hgb on Days 0 and 1 were similar. Higher Day 0 (odds ratio, 0.7 per g/dl; 95%
CI, 0.5-0.99; P = 0.05) and mean hgb (odds ratio, 0.57 per g/dl; 95% CI, 0.38
0.87; P = 0.009) predicted a lower risk of cerebral infarction independent of
vasospasm. There were no associations between hgb and other prognostic variables.
CONCLUSION: We found that SAH patients with higher initial and mean hgb values
had improved outcomes. Higher hgb in SAH patients may be beneficial. The efficacy
and safety of blood transfusions to increase hgb in patients with SAH may warrant
further study.
PMID- 17038944
TI - Cognitive functioning in patients with cerebral aneurysms measured with the mini
mental state examination and the telephone interview for cognitive status.
AB - BACKGROUND: Clinicians and researchers use brief instruments, such as the Mini
Mental State Examination (MMSE) and the Telephone Interview for Cognitive Status
(TICS), to measure cognitive functioning in patients with cerebral aneurysms.
MMSE and TICS scores are often dichotomized to classify patients as cognitively
impaired or not. Frequently, after an initial MMSE face-to-face evaluation, the
TICS is used for follow-up assessments by telephone. METHODS: A cross-sectional
cohort of patients with cerebral aneurysms completed the MMSE at baseline and the
MMSE or TICS at the 12-month follow-up examination. Multivariate logistic
regression adjusting for demographics was used to model cognitive impairment.
MMSE and TICS results were compared using the MMSE as the "gold standard."
RESULTS: Eleven out of 171 (6%) patients had baseline MMSE scores less than 24,
indicating cognitive impairment. Multivariate analysis showed that a history of
subarachnoid hemorrhage was associated with cognitive impairment measured with
the MMSE (odds ratio, 13.9; P = 0.021; C statistic = 0.87); there was no
relationship between subarachnoid hemorrhage or treatment and TICS cognitive
impairment (i.e., score < 27). In patients without recent or interim invasive
interventions that might affect cognition (n = 65), raw baseline MMSE and 12
month TICS scores had fair correlations (r = 0.30, P = 0.015); however,
dichotomized scores had poor agreement, and TICS sensitivity and positive
predictive value was 0% compared with the MMSE. CONCLUSION: The MMSE may be more
sensitive than the TICS to the effects of subarachnoid hemorrhage on cognitive
functioning. Raw MMSE and TICS scores are well correlated, but dichotomized MMSE
and TICS scores are probably not interchangeable in this patient population.
PMID- 17038945
TI - Use of heparin-coated stents in neurovascular interventional procedures:
preliminary experience with 10 patients.
AB - OBJECTIVE: Currently, there is minimal published data on the use of heparin
coated stents in the neurovasculature; however, these stents have a proven
clinical record in the treatment of coronary disease. This article details our
experience with the safety and technical aspects of stent deployment in the first
10 patients who had heparin-coated stents placed in the intracranial and cervical
vasculature and the preliminary follow-up in most cases. METHODS: We
retrospectively reviewed the clinical history, intra- and periprocedural data,
and imaging for the patients who received heparin-coated stents in the cervical
and intracranial vasculature for cerebrovascular disease between October 2002 and
October 2003. RESULTS: Thirteen heparin-coated stents were placed in 10 patients.
Seven out of the 10 patients had heparin-coated stents placed in the posterior
circulation; the remaining three patients had stents placed in the anterior
circulation. Four patients had stents placed intracranially. There was no acute
or subacute in-stent thrombosis and no procedure-related complications. Follow-up
was performed on most patients, with no clinical symptoms attributable to
restenosis in any patient. CONCLUSION: This small series suggests that heparin
coated stents are safe for use in the treatment of cervical and intracranial
atherosclerotic disease. Longer-term follow-up is needed to study the heparin
coating effect on in-stent restenosis rates and to assess the long-term
durability and clinical efficacy of this stent. The use of drug-coated stents in
the cerebrovascular circulation is an area that warrants further investigation.
PMID- 17038946
TI - A randomized trial of synthetic patch versus direct primary closure in carotid
endarterectomy.
AB - OBJECTIVE: To define whether or not direct microscopic closure with or without
the use of a vascular patch is advantageous in terms of clinical outcome and late
vessel occlusion rates after microsurgical carotid endarterectomy. METHODS: Three
hundred thirty-eight elective carotid endarterectomies in 315 patients were
randomized to direct arteriotomy or closure with a polyester collagen-coated
vascular patch. Ten procedures did not follow the randomization process because
of technical difficulties and were excluded. Vessel patency (duplex ultrasound)
and outcome were assessed during and immediately after surgery and at 4 and 12
months after surgery. RESULTS: Four-month ultrasound assessment (n = 321)
identified five occluded vessels: two in the patch group (n = 149) and three in
the direct closure group (n = 172). Six patients in the patch group had died or
were significantly disabled at 4 months, compared with five in the direct closure
group. At the 12-month assessment (n = 313), eight vessels had occluded: five
from the patched group (n = 146) and three from the direct closure group (n =
167). Eight patients in the patch group had died or were significantly disabled,
compared with four in the direct closure group. No statistically significant
difference between the two groups in terms of vessel occlusion, morbidity, or
mortality was seen (P > 0.1). CONCLUSION: No difference in vessel patency and
clinical outcome has been identified after microscopic patch angioplasty and
direct arteriotomy repair. The authors conclude that there is no benefit from the
routine use of patch angioplasty in microscopic carotid endarterectomy.
PMID- 17038947
TI - Unilaterally symptomatic moyamoya disease in children: long-term follow-up of 20
patients.
AB - OBJECTIVE: In unilaterally symptomatic moyamoya disease in children, it remains
controversial whether bypass surgery should be performed on the asymptomatic side
along with on the symptomatic side. We aimed to verify the validity of our
strategy of only performing bypass surgery on the symptomatic side. METHODS:
Among 91 pediatric patients with moyamoya disease who underwent bypass surgery in
our department between 1980 and 2004, 20 with unilateral ischemic symptoms who
were followed for more than 60 months were analyzed in the present study.
Initially, we only performed bypass surgery on the symptomatic side for all 20
patients. Among these 20 patients, five developed frequent transient ischemic
attacks in the initially asymptomatic side and underwent a second bypass surgery
on that side (Group A), eight developed sporadic transient ischemic attacks and
were followed up without surgery (Group B), and seven did not experience any
ischemic symptoms on the asymptomatic side (Group C). RESULTS: In total, 18
patients progressed well without cerebral infarctions after their last surgery,
although some showed deterioration of angiographic stenosis and a transient
decrease in the regional cerebral blood flow or cerebral perfusion reserve. One
patient in Group A had an intraventricular hemorrhage 5 years after the second
operation, and one in Group B had a minor stroke on the initially asymptomatic
side. CONCLUSION: In unilaterally symptomatic moyamoya disease, bypass surgery
for the asymptomatic side can be delayed until the development of ischemic
symptoms, such as frequent transient ischemic attacks.
PMID- 17038948
TI - Ventriculoperitoneal shunting of idiopathic normal pressure hydrocephalus
increases midbrain size: a potential mechanism for gait improvement.
AB - OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is characterized by a
classic clinical triad of symptoms, including dementia, urinary incontinence, and
gait disturbance. Recent work has demonstrated that the maximal midbrain
anteroposterior (AP) diameter is significantly smaller in patients with INPH than
in healthy, age-matched controls. The current study was undertaken to determine
the effect of ventriculoperitoneal shunt placement on midbrain dimensions in INPH
patients. METHODS: Twelve consecutive INPH patients undergoing
ventriculoperitoneal shunt placement with pre- and postoperative computed
tomographic scans at the Columbia University Medical Center were enrolled. Each
patient's pre- and postoperative maximum AP and left-to-right diameters of the
midbrain at the pontomesencephalic junction were independently measured in a
blinded fashion by two of the authors. The average value of each dimension was
computed by calculating the mean values of the measurements of the two observers.
RESULTS: Both the mean AP diameter (preoperative mean, 2.06 +/- 0.04 cm;
postoperative mean, 2.27 +/- 0.05; P = 0.0007) and left-to-right diameter
(preoperative mean, 2.80 +/- 0.07; postoperative mean, 3.03 +/- 0.08; P = 0.0029)
increased from pre- to postoperative imaging. The approximate cross-sectional
area determined as the product of AP and left-to-right diameters also increased
from pre- to postoperative images (preoperative mean, 5.79 +/- 0.22 cm;
postoperative mean, 6.90 +/- 0.25 cm; P = 0.00049). CONCLUSION: This study
provides supportive evidence that midbrain cytoarchitecture may play a role in
the pathophysiology and post-ventriculoperitoneal shunt gait improvement of INPH
patients.
PMID- 17038949
TI - Postoperative pain management after craniotomy: evaluation and cost analysis.
AB - OBJECTIVE: Patients undergoing craniotomies have traditionally received opiates
for the management of their postoperative pain. The use of narcotic pain
medications can be costly, can decrease early walking, can lengthen hospital
stay, and can alter a patient's neurological examination results. The use of
alternative pain medications such as cyclooxygenase-2 (COX-2) inhibitors may
benefit patients by resolving many of these issues. Compared with traditional
nonsteroidal anti-inflammatory drugs, these anti-inflammatory medications may be
used safely in neurosurgical patients because of their selective inhibition of
the COX-2 enzyme, which avoids the platelet dysfunction caused by other
nonsteroidal anti-inflammatory drugs. METHODS: A randomized, single-blinded
prospective study was used to evaluate the efficacy of alternative pain
management strategies for patients who have undergone craniotomy. Twenty-seven
patients were randomly assigned to a control group (n = 13) receiving narcotics
alone or an experimental group (n = 14) receiving a COX-2 inhibitor in addition
to narcotic pain medications. RESULTS: The narcotics group was noted to have
statistically significantly higher visual analog scale scores, increased length
of stay, and increased narcotic use compared with the COX-2 group. The narcotics
group also had increased hospitalization costs when compared with the COX-2
group. CONCLUSION: The use of scheduled atypical analgesics, such as COX-2
inhibitors, in addition to narcotics for the management of postoperative pain
after craniotomy may provide better pain control, may decrease side effects
associated with narcotic pain medications, may encourage earlier walking, and may
reduce total hospitalization costs.
PMID- 17038950
TI - Accessory nerve to suprascapular nerve transfer to restore shoulder exorotation
in otherwise spontaneously recovered obstetric brachial plexus lesions.
AB - OBJECTIVE: A systematic follow-up of infants with an obstetric brachial plexus
lesion of C5 and C6 or the superior trunk showing satisfactory spontaneous
recovery of shoulder and arm function except for voluntary shoulder exorotation,
who underwent an accessory to suprascapular nerve transfer to improve active
shoulder exorotation, to evaluate for functional recovery, and to understand why
other superior trunk functions spontaneously recover in contrast with
exorotation. METHODS: In 54 children, an accessory to suprascapular nerve
transfer was performed as a separate procedure at a mean age of 21.7 months.
Follow-up examinations were conducted before and at 4, 8, 12, 24, and 36 months
after operation and included scoring of shoulder exorotation and abduction.
Intraoperative reactivity of spinatus muscles and additional needle
electromyographic responses were registered after electrostimulation of
suprascapular nerves. Histological examination of suprascapular nerves was
performed. Trophy of spinatus muscles was followed by magnetic resonance imaging
scanning. The influence of perinatal variables and results of ancillary
investigations on outcome were evaluated. RESULTS: Exorotation improved from 70
degrees to functional levels exceeding 0 degrees, except in two patients.
Abduction improved in 27 patients, with results of 90 degrees or more in 49
patients. Electromyography at 4 months did not show signs of denervation in 39
out of 40 patients. Intraoperative electrostimulation of suprascapular nerves
elicited spinatus muscle reaction in 44 out of 48 patients. Histology of
suprascapular nerves was normal. Preoperative magnetic resonance imaging scans
showed only minor wasting of spinatus muscles in contrast with major wasting
after successful operations. CONCLUSION: An accessory to suprascapular nerve
transfer is effective to restore active exorotation when performed as the primary
or a separate secondary procedure in children older than 10 months of age.
Contradictory spontaneous recovery of other superior trunk functions and
integrity of suprascapular nerves, as well as absence of spinatus muscle wasting
direct to central nervous changes are possible main causes for the lack of
exorotation.
PMID- 17038951
TI - Microsurgical anatomy of the central retinal artery.
AB - OBJECTIVE: To define the microsurgical anatomy of the central retinal artery
(CRA) and to provide a guide to avoiding damage to it during surgery. METHODS:
The anatomic characteristics of the CRA and small arteries distributed to the
optic sheath were examined in 109 orbits. The origin, course, and site of entry
of the artery into the optic sheath and the distance between the orbital apex and
the site of entry into the sheath were examined. RESULTS: The CRAs originated
directly from the intraorbital ophthalmic artery or in a common trunk with a
posterior ciliary or a muscular branch. The CRAs most commonly originated on the
inferomedial side of the ophthalmic artery an average of 8.4 mm distal to the
orbital end of the optic canal. They penetrated the optic sheath near the
junction of the middle and anterior thirds of the length of the intraorbital
optic nerve an average of 18.6 mm distal to the optic canal. More than 70% of
CRAs penetrated near the midline of the lower surface of the optic sheath, 21%
entered the inferomedial surface, and 7% the inferolateral or lateral surface of
the optic sheath. Only one CRA gave off a branch before penetrating the nerve.
CONCLUSION: The CRA is at risk of being damaged or occluded during procedures
involving a large part of the orbit. Procedures directed along the lower half of
the proximal two-thirds of the optic sheath have the greatest risk of
interrupting the artery.
PMID- 17038952
TI - Optic strut as a radiographic landmark in evaluating neck location of a
paraclinoid aneurysm.
AB - OBJECTIVE: The optic strut (OS) is a candidate landmark in computed tomographic
(CT) angiographic scans for the discrimination of intradural and
extradural/intracavernous aneurysms involving the paraclinoid segment of the
internal carotid artery. The goal of this study is to examine and confirm the
qualifications of the OS as a landmark in CT angiographic scans for the
preoperative evaluation of aneurysms in this region. METHODS: Seventeen
consecutive patients with 18 unruptured paraclinoid aneurysms who underwent
preoperative CT angiography scans and direct surgery between 1998 and 2005 were
evaluated retrospectively. We focused on the relationships of the necks of
aneurysms to the OS in CT angiographic scans and that of the necks to proximal
dural rings during intraoperative examinations. RESULTS: Direct surgery revealed
that 14 aneurysms, the necks of which were distal to the OS on CT angiographic
scans, arose distal to the proximal dural rings. All aneurysms were clipped,
except one exhibiting calcification of the neck. Three aneurysms, for which the
neck was proximal to the OS on CT angiographic scans, revealed only a portion or
nothing of their domes instead of their necks through the proximal dural rings
after dissection of the distal dural rings. Dome coating with fibrin glue and a
piece of muscle tissue or mere exploration was performed. Another aneurysm, of
which the neck straddled the OS on CT angiographic scans, was found to arise
across the proximal dural ring. Clipping of the neck was performed after
dissection of the proximal dural ring. Of the source images of CT angiographic
scans, the axial images were the most useful in evaluating the relationship of
the neck of an aneurysm to the OS. CONCLUSION: On CT angiographic scans, the OS
is a precise identification of the proximal dural ring that forms the superior
border of the cavernous sinus. The aneurysms whose necks arise obviously distal
to the OS on CT angiographic scans are able to be clipped without dissection of
the proximal dural ring.
PMID- 17038953
TI - Magnetic resonance imaging of the craniocervical junction at 3-T: observation of
the accessory atlantoaxial ligaments.
AB - OBJECTIVE: Instability of the craniocervical junction can cause neurological
sequelae or pain. Stability of this region depends on extensive ligamentous
support structures, most of which are well studied by magnetic resonance imaging
(MRI) scanning. Although the contribution of the accessory atlantoaxial ligament
to rotational stability has been described, this ligament has not been identified
by imaging. Therefore, we investigated the imaging characteristics of this
ligament and its relationship to the ligamentous complex of the craniocervical
junction using the high resolution offered by 3-T MRI scans. METHODS: Ten healthy
volunteers underwent MRI scanning at 3-T to determine the normal anatomy of this
ligament. RESULTS: The atlantoaxial (C1-C2) segment of the ligament was
identified in all 10 subjects bilaterally and symmetrically. Its mean dimensions
were 2.8 x 1.8 mm. In four out of 10 subjects, the occipitoatlantal (C0-C1)
segment was observed. At this level, the mean dimensions of the ligament were 1.6
x 1.2 mm on the right and 1.8 x 1.4 mm on the left. Its size varied between the
right and left sides. CONCLUSION: The accessory atlantoaxial ligament can be
visualized using high-resolution MRI scans at 3-T. The ligament was most
consistent and robust at C1-C2. The ligament may, therefore, contribute to
rotational stability at this level. Future studies will determine the
biomechanical importance of this ligament, especially in the setting of trauma.
PMID- 17038954
TI - Caspase-3-dependent apoptosis in middle cerebral arteries in patients with
moyamoya disease.
AB - OBJECTIVE: Moyamoya disease (MMD) is a cerebrovascular occlusive disease
characterized by progressive stenosis or occlusion at the distal ends of
bilateral internal arteries. In MMD, a decreased number of medial smooth muscle
cells in these vessels was previously reported. In this study focusing on the
mechanism of remodeling in intracranial arterial walls of patients with MMD, we
first collected tiny pieces of the wall of the middle cerebral artery (MCA) from
patients with MMD and then analyzed them by immunohistochemical methods. METHODS:
Ten patients underwent surgical procedures for the treatment of standard
indications of MMD at Kyoto University Hospital. Specimens of MCA were obtained
from these MMD patients during the surgical procedures. MCA samples were also
obtained in the same way from control patients. The samples were analyzed by
immunohistochemical methods. RESULTS: MCA specimens from MMD patients had a
thinner media than control specimens. Immunoreactivities indicating single
stranded DNA and cleaved caspase-3 were higher in MMD samples than in control
ones and were located in the smooth muscle cells of the media. CONCLUSION: Our
results indicate that apoptosis, as evidenced by activated caspase-3, occurred in
the media of the MCA of MMD patients. Thus, the MCA specimens from MMD patients
had thinner vascular walls than specimens from controls.
PMID- 17038955
TI - Defective receptor expression and dendritic cell differentiation of monocytes in
glioblastomas.
AB - OBJECTIVE: Better characterization of the changes that occur in the circulating
monocytes of patients with glioblastoma has become more important recently as
monocyte-derived dendritic cells are used as adjuvants in the development of
glioma vaccines. This study seeks to develop understanding of the phenotypic
changes that occur in circulating monocytes of patients with intracranial cancer
and to assess the ability of these cells to differentiate into mature dendritic
cells. METHODS: Monocyte expression levels of HLA-ABC, HLA-DR, CD86, ICAM-1,
TNFRII, and GMCSFR were compared between three cohorts: patients with
intracranial glioblastoma (n = 15), patients with intracranial metastases (n =
9), and a group of healthy controls (n = 10). Monocytes were then tested for
their ability to differentiate into mature dentritic cells based on morphology,
CD83 expression and high levels of co-stimulatory molecules. RESULTS:
Comprehensive analysis of monocyte receptor expression demonstrated significantly
reduced HLA-ABC, HLA-DR, CD86, ICAM-1, and TNFRII in patients with glioblastoma
but not in patients with intracranial metastases compared with a group of healthy
controls. GMCSFR expression was significantly reduced in both patients with
glioblastoma and intracranial metastases. Additionally, the monocytes of patients
with glioblastoma showed a reduced capacity to differentiate into mature
dendritic cells as identified by CD83 expression, receptor expression, and
morphology. CONCLUSION: Peripheral monocytes are phenotypically altered in the
setting of glioblastoma and display a reduced functional capacity to
differentiate into mature dendritic cells.
PMID- 17038956
TI - Long-term histological and scanning electron microscopy results of endovascular
and operative treatments of experimentally induced aneurysms in the rabbit.
AB - OBJECTIVE: Treatment strategies of cerebral aneurysms include surgical clipping
and endovascular therapies. To determine the long-term results of these
therapeutic strategies, the vessel wall reaction close to the former aneurysm was
studied according to the assumption that an intact endothelial layer over the
former aneurysm neck constitutes complete vessel wall reconstruction and stable
aneurysm obliteration. METHODS: Aneurysms were created in 40 rabbits by
intraluminal elastase incubation of the common carotid artery. Five animals each
were assigned to the following groups: untreated, porous stents, polyurethane
covered stentgrafts, porous stents with subsequent coiling. Ten animals were
treated with coils alone, 10 with clips. After 6 months, angiography, histology,
and scanning electron microscopy was performed. RESULTS: Porous stents did not
obliterate the aneurysm, whereas stentgrafts did; in-stent stenosis of up to 60%
was present because of neointimal multilayer proliferation. After coiling, the
aneurysm dome was occluded with fibrinous and collagenous material, whereas the
aneurysm neck was not covered by an endothelial lining. Coil loops lay bare
within the vessel, with fresh thrombus material on their surface. After clipping,
a thin layer of endothelial lining bridging the two attached vessel walls was
present, thereby completely obliterating the aneurysm and reconstructing the
vessel wall. CONCLUSION: This study demonstrates complete and stable aneurysm
obliteration with vessel wall reconstruction after clipping, a sufficient
obliteration of the aneurysm dome using endovascular techniques, but a failed
healing response of the aneurysm neck that might correlate to its associated
higher risk of rebleed. Whether or not this is counterbalanced by the better
immediate outcome after endovascular treatment remains a matter of debate.
PMID- 17038957
TI - Safety and pharmacokinetics of sirolimus-eluting stents in the canine cerebral
vasculature: 180 day assessment.
AB - OBJECTIVE: We evaluated local and systemic pharmacokinetics and pharmacodynamics
of sirolimus-eluting stents (SES) in canine cerebral vessels. METHODS: SES (1.5 x
8 mm, 79 microg/479 microg sirolimus) and control stents (1.5 x 8 mm stainless
steel with or without polymer) were implanted in canine basilar and ventral
spinal arteries. Animals were sacrificed for local pharmacokinetic (36 animals at
1, 3, 8, 30, 90, 180 days) and pharmacodynamic (60 animals at 3, 30, 90, 180
days) assessment. RESULTS: Postrecovery adverse clinical events were not serious,
requiring no unscheduled treatment. Histologically, brain and spinal cord
sections revealed scattered microinfarcts and minimal gliosis consistent with
postprocedure changes in all four stent-treatment groups. All stented vessels at
all time points demonstrated good luminal patency with low injury and
inflammation scores and no thrombosis of either stented or branch arteries.
Endothelialization was complete in all stent groups by 30 days. Intimal smooth
muscle cell scores were reduced in both SES groups at 30, 90, and 180 days.
Systemic sirolimus levels peaked between 1 and 7 hours postimplant (maximum
concentration, 1.2 +/- 1.47, 79 microg; 4.5 +/- 1.23 ng/ml, 479 microg), then
declined rapidly to 1 ng/ml or less by 96 hours. Peak local tissue sirolimus
levels were 41.5 ng/mg (79 microg) and 65 ng/mg (479 microg). CONCLUSION: SES in
canine cerebral vessels were associated with good luminal patency to 180 days,
with complete endothelialization and no evidence of acute thrombosis. This model
has shown that SES deployed within the brain do not cause neurotoxicity during a
180-day time course, even when exaggerated doses are used. The findings support
the contention that SES are safe to use and maintain patency in cerebral vessels.
PMID- 17038958
TI - The cure of folly or The operation for the stone by Hieronymus Bosch (C. 1450
1516).
PMID- 17038961
TI - Endoscopic fenestration of a symptomatic cavum septum pellucidum: technical case
report.
AB - OBJECTIVE: Cysts of the septum pellucidum (CSPs) may become symptomatic because
of obstruction of cerebrospinal fluid flow, resulting in increased intracranial
pressure and hydrocephalus requiring surgical intervention. Endoscopic
fenestration may be the most effective and least invasive technique to treat this
pathological condition. CLINICAL PRESENTATION: An 11-year-old boy sought
treatment for frequent episodes of severe headache. On examination, he had
papilledema. There was evidence on magnetic resonance imaging scans of a space
occupying CSP with obstructive hydrocephalus. INTERVENTION: The endoscopic
technique of fenestration of both lateral walls of an enlarged CSP via a left
frontal approach under ultrasound guidance using a rigid endoscope was
successful. After surgery, the patient became asymptomatic, his papilledema
resolved, and magnetic resonance imaging scans demonstrated collapse of the walls
of the CSP toward the midline. CONCLUSION: Neuroendoscopic fenestration should be
strongly considered as the treatment of choice for symptomatic CSPs. This
procedure alone can lead to complete resolution of clinical symptoms and
hydrocephalus, can reduce the size of the CSP, and can obviate the need for an
implantable cerebrospinal fluid shunt.
PMID- 17038962
TI - Microsurgery in the removal of a large cerebral hydatid cyst: technical case
report.
AB - OBJECTIVE: Surgery is presently the mainstay in the treatment of cerebral hydatid
cysts, but removal without perforation of the cyst wall is critical. The Dowling
Orlando technique has been the main surgical choice for the intact removal of
intracranial hydatid cysts. Dowling described his technique in 1929, well before
the introduction of the microscope in neurosurgery. Using the operating
microscope has not been reported in the removal of a large hydatid cyst. CLINICAL
PRESENTATION: The case of a 16-year-old male with a large, right parieto
occipital hydatid cyst is presented. INTERVENTION: In this case, surgery was
greatly aided by the use of the microscope in the initial stage of the removal of
the cyst. Cyst extraction during the delivery process was continued without the
aid of the microscope. The cyst was successfully removed intact. CONCLUSION: The
use of the magnification during the early part of the surgery of a hydatid cyst
is extremely helpful because, at a crucial stage of the procedure, it prevents
inadvertent damage of the very thin cyst wall and allows development of the
critical surgical plane.
PMID- 17038963
TI - An assessment of sites where persons go to meet sexual partners in St. James,
Jamaica, using the PLACE method.
AB - OBJECTIVE: The objective of this study was to assess sexual behavior of persons
at risk of HIV infection. GOAL: The goal of this study was to identify sites
where HIV prevention is needed. STUDY DESIGN: Customers at sites where persons
meet new sex partners in St. James, Jamaica, were surveyed. RESULTS: Of 421
sites, 282 men and 200 women (random sample, 23 sites) and 320 men and 265 women
(special sample, 26 sites) were interviewed. Over one fourth of men and 14%
(special) and 4% (random) of women had one or more new sex partners in the last 4
weeks. Seventy-eight percent of men reported condom use at last sex with a new
partner compared with 66% of women. Approximately 50% of respondents reported
condom use at last sex with a regular partner. CONCLUSION: Sites at which people
meet new sex partners were diverse with significant opportunities for prevention.
Commercial and transactional sex are features at many sites.
PMID- 17038964
TI - Measurement of microbicide acceptability among U.S. adolescent girls.
AB - BACKGROUND AND OBJECTIVE: Topical microbicides will only be effective if they are
acceptable to potential users. The purpose of this study is to develop a scale to
evaluate characteristics and aspects of topical microbicides that are important
to adolescent girls. STUDY DESIGN: Girls (n = 207) completed a questionnaire on
perceptions of microbicide-like products. RESULTS: A principal components factor
analysis with a varimax rotation produced a 6-factor solution. The mean factor
scores suggested that girls saw the products positively. Age was positively
correlated with "comparison to condoms" and "comfort while using" factor scores
and inversely correlated with "negative impact on interpersonal relationships"
factor score. Sexually transmitted infection (STI) history was related to higher
scores on the "health benefits" and "pleasure" factors. Age, race/ethnicity, and
STI history were not related to the other factor scores. CONCLUSION: The current
scale shows promise in assessment of microbicide acceptability, and in general,
girls expressed positive views about microbicides.
PMID- 17038967
TI - Outcome measures and surgery for stress urinary incontinence.
AB - A large number of surgical procedures to correct urinary stress incontinence in
the female have been described. There has been wide variablility in reported
success rates. This variablility is due to a number of factors. Papers published
in 1997 that assess outcomes in the treatment of female stress urinary
incontinence illustrate many of the current problems that exist with examining
outcomes, including patient selection, modifications in technique, the definition
of success, how success is measured and when the outcome is assessed.
PMID- 17038965
TI - The efficacy of behavioral interventions in reducing HIV risk sex behaviors and
incident sexually transmitted disease in black and Hispanic sexually transmitted
disease clinic patients in the United States: a meta-analytic review.
AB - OBJECTIVES: Interventions targeting sexually transmitted disease (STD) clinic
patients provide an important opportunity to modify high-risk sex behaviors
related to HIV/STD transmission. Identifying efficacious interventions for blacks
and Hispanics is urgently needed because these 2 groups are disproportionately
affected by the HIV/STD epidemics. GOAL: This meta-analysis evaluates the
efficacy of behavioral interventions in reducing unprotected sex and incident STD
among black and Hispanic STD clinic patients. STUDY DESIGN: Comprehensive
searches, including electronic databases (1988-2004), hand searches of journals
(January 2004 to June 2005), reference lists of articles, and contacts with
researchers, identified 18 randomized, controlled trials meeting the selection
criteria. RESULTS: Interventions significantly reduced unprotected sex (odds
ratio [OR] = 0.77; 95% confidence interval [CI] = 0.68-0.87; 14 trials; N =
11,590) and incident STD (OR = 0.85; 95% CI = 0.73-0.998; 13 trials; N = 16,172).
CONCLUSIONS: Behavioral interventions provide an efficacious means of HIV/STD
prevention for blacks and Hispanics who attend STD clinics.
PMID- 17038968
TI - Results of behavioral treatment for urinary incontinence in women.
AB - Recent research on pelvic muscle exercises, which are known to be effective in
stress and mixed urinary incontinence, has demonstrated that this therapy has a
durable effect. However, the mechanism that creates its efficacy remains unclear.
Transvaginal electrical stimulation has been used to manage stress, urge and
mixed urinary incontinence. Conflicting evidence exists concerning its efficacy
in stress urinary incontinence, but its benefit to women with mixed and urge
incontinence is well established.
PMID- 17038969
TI - Laparoscopic correction of stress urinary incontinence.
AB - The laparoscopic correction of stress urinary incontinence continues to be
evaluated. Early results have been encouraging with cure/dry rates equivalent to
those with traditional suspensions, but with shorter hospitalization and no
significant morbidity. The approach continues to take longer in the operating
room than traditional suspensions, although new innovations and refinements have
shortened the time. We are still lacking long-term outcome data and well
constructed prospective randomized trials. Cost effectiveness studies are also
not consistent.
PMID- 17038970
TI - Sacral neuromodulation in the treatment of the unstable bladder.
AB - Sacral neuromodulation as a treatment for urge incontinence in patients with an
unstable bladder is the subject of ongoing clinical studies. Although
approximately 75% of the patients treated with a permanent sacral foramen
electrode implant have experienced significant improvements, it is now also clear
that there is an initial failure rate of about 25%. Recent studies have pointed
out the importance of improved patient selection on the basis of sex differences,
urodynamic parameters and psychological factors. Also, newer forms of test
stimulation and permanent electrode implantation are being explored in an effort
to improve on the present results.
PMID- 17038971
TI - Use of intravesical capsaicin for urge urinary incontinence and irritative
voiding syndromes.
AB - Intravesical capsaicin has been used in the management of selected patients with
urge urinary incontinence throughout this decade, but the past 12 months has seen
considerable interest in this and related compounds. It is no coincidence that
during the same period the capsaicin receptor was cloned and named the vanilloid
receptor subtype 1 and the European dual centre study of intravesical capsaicin
reported that overall 80% of patients derived some clinical benefit. In spite of
this, ultrapotent capsaicin analogues such as resiniferatoxin, which also
interact with the vanilloid receptor subtype 1, are being studied. Preliminary
reports of the potential advantages of intravesical resiniferatoxin are beginning
to emerge, and in the future drugs that manipulate the vanilloid receptor may
become universally important in the management of neurogenic overactive bladders.
PMID- 17038974
TI - Stones and bones: bone resorption and metabolism in stoneformers.
AB - Abnormalities of bone metabolism and osteopenia (which may be progressive) are
features of idiopathic calcium stone disease. This abnormal bone metabolism may
be mediated by increased levels of, or responsiveness to, calcitriol or
cytokines, including interleukin-1. Bone resorption may be reduced experimentally
with bisphosphonates, but for clinical management an appropriate adjustment of
dietary calcium intake may be the method of choice to ameliorate bone loss.
PMID- 17038973
TI - Crystal-macromolecule interactions in urolithiasis: lessons from healthy
biomineralization systems.
AB - Recent advances in understanding the molecular level mechanisms that control
biomineralization and organic-inorganic interactions in urolithiasis are
reviewed, and the validity of drawing parallels between them are considered. The
multifunctional nature of many biomineralization molecules, particularly
proteins, and the different roles they play in and out of solution suggest
avenues for resolving the apparent paradox that urinary macromolecules have been
observed both to inhibit and to promote stone formation.
PMID- 17038975
TI - Molecular basis of inherited renal lithiasis.
AB - Idiopathic calcium oxalate stone formation results from an interaction between
genetic and environmental factors. Clearly identifiable risk factors for the
disease that have a significant genetic influence are the excretions of calcium,
oxalate and citrate. Candidate genes that may be responsible for these effects
have been proposed. With the large-scale sequencing of the human genome and the
identification of genetic polymorphisms, it is only a matter of time before these
genes and the sequence differences within them that are associated with
susceptibility to the disease are conclusively identified.
PMID- 17038976
TI - Pathophysiology of idiopathic hypercalciuria: the current concept.
AB - During past decades it became fashionable to address individual facets of
idiopathic hypercalciuria selectively and independently in the laboratory, thus
preparing for the almost impossible conciliation of these fragments in the
future. In this review a unifying concept is presented, which places excessive
meat protein intake at the centre of the scheme and links it to other facets of
the phenotype of the disease, such as the genetic component of bone
demineralization, fasting hypercalciuria and excessive production of 1,25
dihydroxyvitamin D, as well as of various cytokines.
PMID- 17038977
TI - An evidence-based approach to hypercalciuria: is it really necessary for the
study of the role of calcium in urolithiasis?
AB - An abnormally raised 24-h urinary excretion of calcium has long been regarded as
a common feature of calcium stone disease. However, hypercalciuria can be defined
only by reference to a range of values measured in a representative population of
individuals who have never suffered from stone disease. To date, there have been
significant flaws in all published studies reporting normal ranges for daily
urinary calcium excretion. There is no doubt that additional, carefully performed
and documented investigations need to be undertaken to establish what is truly
abnormal for a given population; the persistent use of arbitrarily defined limits
may be hindering rather than helping to unravel the role of calcium in the
pathogenesis of calcium stones.
PMID- 17038978
TI - Drug-induced urolithiasis.
AB - Drugs can cause renal stone formation either by raising excretion rates of
naturally occurring stone components or by directly precipitating within the
urinary tract. In large series of analysed renal stones, the overall frequency of
drug-induced urolithiasis is less than 0.5%. Five clinical presentations of drug
induced crystallization in the kidneys can be recognized: asymptomatic
crystalluria, symptomatic crystalluria; stone passage; obstructive uropathy and
tubulointerstitial nephritis. In the current literature review, the protease
inhibitors used for treatment of patients infected with the human
immunodeficiency virus stand out as a new class of drugs that frequently causes
crystallization within the urinary tract. The most widely used compound,
indinavir, may lead to crystalluria and renal stone formation in up to 50% of
patients, and occasionally also causes acute renal failure caused by obstructive
uropathy or tubulointerstitial nephritis. On the other hand, ritonavir appears
more often to induce (reversible) acute renal failure than stone formation.
PMID- 17039012
TI - Current world literature.
PMID- 17039014
TI - Surgery in advanced and metastatic renal cell carcinoma.
AB - Curative surgery in more advanced renal cell carcinoma is limited to solitary
metastases or regional disease. Response to systemic immunotherapy continues to
be reported; however, most responses are limited and not durable. Only
randomized, prospective clinical trials will prove the efficacy of systemic
therapy.
PMID- 17039015
TI - Prostate cancer: epidemiology and risk factors.
AB - After years of rapid increase, the incidence of prostate cancer has begun to
decline in certain areas in the USA. Although these temporal trends are
consistent with the impact of screening, it still remains to be shown that early
detection programmes and screening will result in a reduced mortality rate from
this disease. A positive family history of prostate cancer has been established
as an important risk factor, and recent research supports and points to the
existence of a subgroup of prostate cancer families with a hereditary form of the
disease. Diet is another well-known risk factor. Recently, it has become evident
that nutritional factors might both prevent the progression of prostate cancer or
induce it.
PMID- 17039016
TI - Neoadjuvant therapy in localized prostate cancer before surgery and radiotherapy.
AB - Neoadjuvant hormonal therapy brings the possibility of improving the results of
radical treatment of clinically localized prostate cancer. While the advantages
of this therapy combined with radiotherapy and cryosurgery are encouraging, as
yet the positive effects of initial hormonal ablation before radical
prostatectomy are still not proven.
PMID- 17039017
TI - Brachytherapy in localized prostatic cancer: 100 years of radium.
AB - Contemporary series of brachytherapy in localized prostate cancer show promising
early results attributable to improved patient selection and technical
refinements in treatment modalities. These innovations consist essentially of
precise three-dimensional radioactive dose-distribution planning and source
placement, thus solving the problem of possible under-dosage encountered in open
brachytherapy.
PMID- 17039018
TI - The clinical importance of free prostate-specific antigen (PSA).
AB - The proportion of free prostate-specific antigen (PSA) in serum relative to total
PSA (F/T) is lower in patients with prostate cancer than in those with elevated
levels of PSA due to benign prostatic disease. When applied to early diagnosis
and screening for prostate cancer, the proportion of free PSA can be used to
reduce the number of false-positive results by 20-40%. The utility of F/T is
better in men with a small prostate volume, i.e. in relatively young men, who are
most likely to benefit from early diagnosis and treatment of prostate cancer. The
concentrations of PSA and especially free PSA are affected by considerable intra
individual variation and sample stability. Assay standardization is variable and
it is therefore important to establish reference values for the methods used.
Better control of these factors is likely to improve the diagnostic accuracy. The
utility of determining free PSA can be improved by evaluating the combined impact
of free and total PSA by logistic regression analysis or neural networks.
PMID- 17039019
TI - Clinical implications of prostate-specific antigen (PSA).
AB - Prostate-specific antigen(PSA) is currently the tumour marker of choice for
prostatic carcinoma. This article examines the current literature on the
application of PSA for cancer detection (concentrating on values of PSA in the
normal and 'grey' areas of 2.5-10 ng/ml), in staging of the disease and
prediction of treatment response. These areas in particular have been refined by
the use of PSA indices (PSA density, velocity, age ranges) and the article
focuses on the recent studies analysing their standing in clinical practice.
PMID- 17039020
TI - Immediate adjuvant intravesical chemotherapy after transurethral resection of
bladder tumor.
PMID- 17039021
TI - Emerging strategies in the treatment of testis cancer.
AB - The state of the art in the study and therapy of germ-cell tumors of the testis
is reflected in this year's literature. For the majority of patients with germ
cell tumors, the therapeutic dilemma no longer relates to cure. For such patients
with low-volume non-seminomatous germ-cell tumors of the testicle and those with
a pure seminoma, therapeutic dilemmas relate more to selection of the appropriate
therapy to achieve cure, the toxicity of therapy, and the precise prediction of
outcome. However, a high cure rate cannot be anticipated with equal frequency in
those patients with high-volume non-seminomatous germ-cell tumors of the
testicle.
PMID- 17039022
TI - New chemotherapy regimens for metastatic bladder cancer.
AB - M-VAC remains the standard of care for metastatic transitional cell carcinoma
(TCC), but its limitations include significant toxicity and infrequent durable
disease-free survival. Recent investigation has focused on the identification of
novel chemotherapeutics with single-agent activity in metastatic TCC and on their
incorporation into more active combination regimens. Paclitaxel, gemcitabine and
ifosfamide are among the most active new agents. Numerous phase II trials of
novel combinations have yielded promising preliminary results. Longer follow-up
and results from randomized trials will be necessary to determine the impact of
newer chemotherapy regimens on survival.
PMID- 17039023
TI - Developments in bladder cancer monitoring.
AB - The exclusive reliance on standard urinary cytology and cystoscopy for early
diagnosis and monitoring of bladder cancer is now challenged by innovative
techniques. A variety of urine tests employing immunostaining promise to enhance
the value of cytological examination. Detection of tumor-associated antigens and
substances present in the urine of patients harboring bladder cancer has reached
a high degree of sophistication. Laboratory-based tests offer the possibility of
early prediction of recurrence with a significant degree of accuracy. Equally
exciting is the availability of rapid urine tests (point-of-care) that offer
better sensitivity and specificity than cytology, deliver immediate results and
provide an indication of the degree of tumor differentiation.
PMID- 17039024
TI - Superficial transitional cell carcinoma: bacillus Calmette-Guerin (BCG) and other
intravesical agents.
AB - Adjuvant immuno- and/or chemotherapy intravesically has become a standard at
least for patients with intermediate or high risk for recurrence. Whereas in the
past cystectomy was a first-line therapy for patients with carcinoma in situ or
high-grade T1 bladder tumor, radical surgery is today reserved for non-BCG
responders or early recurrent disease.
PMID- 17039025
TI - Muscle-invasive transitional cell carcinoma of the bladder: strategies for
bladder preservation.
AB - For patients with invasive bladder cancer, radical cystectomy remains the gold
standard of treatment. However, based upon success with combination chemotherapy,
physicians have begun to use this modality in an integrated approach with
radiotherapy. This approach is of interest for elderly patients with poor medical
conditions and for younger patients who may prefer to retain their bladders.
Thorough transurethral resection of the bladder followed by chemotherapy with or
without radiotherapy has become the focus of several studies. Bladder-conserving
therapy may be offered to selected patients with invasive bladder cancer as a
viable alternative to radical cystectomy.
PMID- 17039063
TI - Current world literature.
PMID- 17039065
TI - Neonatal hydronephrosis.
AB - With fetal abnormalities diagnosed during maternal ultrasound becoming more
commonplace, the management of neonatal hydronephrosis has become one of the most
interesting and controversial subjects in pediatric urology. Although it is
recognized that obstruction must be treated, it is also clear that hydronephrosis
may well exist without significant obstruction. Numerous experimental and
clinical studies of the urinary tract have failed to lead to a clear consensus.
Our approach consists of careful observation of patients with moderate
hydronephrosis in well functioning kidneys. In patients with reduced function or
a renal pelvic diameter of greater than 3 cm and dilated calyces, we lean more
towards surgical intervention. Overall, an individualized approach is necessary.
PMID- 17039066
TI - Genital reconstruction.
AB - Genital reconstruction is necessary in various types of congenital malformations.
Although various surgical procedures may be used depending on the anomaly, the
basic principles are the same. Three groups of pathology are discussed:
hypospadias, ambiguous genitalia and exstrophy-epispadias complex. Progress
continues to be made in modifying older techniques and creating new ones. Some
investigators have focused on pain control and dressing materials. There is still
much work to be done in this challenging area.
PMID- 17039067
TI - Infections and vesicoureteral reflux.
AB - Vesicoureteral reflux (VUR) is a common condition in children. It may cause and
maintain urinary tract infections, eventually leading to progressive renal damage
and end-stage renal disease. Ideally, VUR should be detected and treated before
renal scarring occurs. Although fetal hydronephrosis on antenatal ultrasound may
be the first indicator, the role of further diagnostic investigations in these
newborns is still controversial. Because VUR is an inherited condition, offspring
of women with a family history of VUR and urinary tract infection should be
screened closely for early detection of VUR. Once diagnosed, however, the optimal
management of VUR (i.e. medical or surgical treatment) remains controversial.
Evidence-based treatment recommendations, like the American Urological
Association guidelines, may aid physicians in their therapeutic decision making,
but cannot replace personal experience or surgical skill.
PMID- 17039068
TI - Enuresis, voiding dysfunction and neurogenic bladder in children.
AB - This review covers bladder dysfunction in children. A significant amount of work
has been done in the past year with regard to enuresis. The International
Children Continence Society discussed the issues of bladder dysfunction,
including enuresis, and this review covers the findings of that meeting. It also
covers the articles that have been published on neurogenic bladder dysfunction as
well as on posterior urethral valves.
PMID- 17039069
TI - Renal diseases and transplantation in children.
AB - The diseases that are most commonly responsible for renal damage and end-stage
renal disease are unique in children. The devastating effect of chronic renal
failure on the mental and physical development of children offers many
challenging management problems. Although less than perfect, successful renal
transplantation is considered the best available treatment option for children,
with the alternative of dialysis often made difficult by access problems, growth
retardation and renal osteodystrophy. Children comprise between 5 and 8% of our
transplant programme, and we consider transplantation and dialysis to be
complementary rather than competitive.
PMID- 17039070
TI - Paediatric oncology.
AB - Recent research into paediatric urologic oncology has identified a number of
certain subgroups of neuroblastoma and Wilms' tumour, which allows a more
tailored treatment of the individual child with respect to treatment sequelae and
finance issues. The importance of surgery, radiotherapy and cytostatic treatment
has to be individualized. The controversies regarding the management of
rhabdomyosarcoma of the bladder and the prostate remain unresolved.
PMID- 17039072
TI - Vasectomy reversal in the age of intracytoplasmic sperm injection.
AB - The advent of intracytoplasmic sperm injection has revolutionized the treatment
of male infertility and offers an alternative to vasectomy reversal as a
treatment option for post-vasectomy infertility. Issues including morbidity, cost
and therapeutic outcomes are, however, important considerations for both
treatment options. Vasectomy reversal should be considered the ideal option for
couples less than 15 years since vasectomy, couples interested in more than one
child, couples without in-vitro fertilization insurance coverage and couples with
no interest in assisted reproductive techniques. Intracytoplasmic sperm injection
may be considered as the primary option for those couples with an older female
partner especially if bilateral vasoepididymostomy may be required.
PMID- 17039073
TI - Current concepts in the management of post-radical prostatectomy impotence.
AB - Erectile dysfunction after radical retropubic prostatectomy has a multifactorial
aetiology, including both neurogenic and vasculogenic factors. Postoperative
potency is improved with preservation of the neurovascular bundles in a nerve
sparing procedure. Preoperative and intraoperative identification and
preservation of accessory pudendal arteries may also improve postoperative
potency rates. The early institution of treatment with intracavernous alprostadil
appears to improve postoperative potency rates. Treatment with newer therapeutic
agents, such as Sildenafil and Invicorp, are both efficacious and well tolerated.
PMID- 17039074
TI - Venous grafting for the correction of penile curvature in Peyronie's disease.
AB - A number of procedures have been developed to correct penile deformity secondary
to Peyronie's disease. In many cases, tunica-shortening procedures have had
reasonable success. The most popular of these are tunical plication and Nesbit's
wedge resection. However, these procedures shorten the penis and do not correct
the hourglass deformity. Tunica-lengthening by using autologous or synthetic
materials has been reported with varying success. However, notable shortcomings
including graft contracture, recurrence, and impotence have been reported. This
review describes our experience with tunica incision and venous grafting.
PMID- 17039075
TI - Fertility considerations in the patient with testis cancer.
AB - Fertility is an important aspect in the quality of life of patients surviving
testis cancer. The question of future fertility should be considered before
treatment commences, and the patient's wishes may require modification of
therapeutic regimens. The biggest improvement in the management of male
infertility over the past 10 years has been the introduction of intracytoplasmic
sperm injection (ICSI). This review gives a perspective of these issues, together
with an outline of recent papers on the subject.
PMID- 17039076
TI - Viagra: what's all the fuss about?
PMID- 17039077
TI - Current world literature.
PMID- 17039079
TI - SLE in a United States-Mexico border community.
AB - This report describes the results of a clinic-based study conducted to verify a
community-reported excess prevalence of systemic lupus erythematosus (SLE) and a
possible connection between ethnicity and environmental factors in the reporting
of SLE in the United States-Mexico border town of Nogales, Arizona. A community
group in Nogales reported 37 cases of SLE in its community, suggesting a
prevalence rate of 200 per 100,000. This report describes 19 definite and 7
probable cases of SLE using the 1982 American College of Rheumatology criteria.
All definite and probable cases were self-identified, Mexican-American females.
This yields a prevalence rate of 94 per 100,000, among the highest reported to
date. The majority of cases resided within 3 miles of the United States-Mexico
border and within 1 mile of the polluted Nogales Wash or ground wells with
documented toxins. It remains to be determined whether this confirms that SLE is
more common in Mexican-Americans or whether environmental factors, especially
pollutants, are predominantly responsible. In addition to the need to be aware
about the apparent increased risk of SLE in many Latin-Americans, clinicians
should ask about possible environmental factors.
PMID- 17039080
TI - Serum and urine nitrite and citrulline levels among patients with systemic lupus
erythematosus: a possible addition to activity parameters?
AB - Nitric oxide (NO) plays a significant role in the inflammatory process and has
been implicated in several autoimmune disorders. This study was carried out
prospectively to estimate the levels of nitrite and citrulline in the serum and
urine, as surrogate markers of NO production, among patients with systemic lupus
erythematosus (SLE). Forty-seven patients and 44 age- and sex-matched, healthy
volunteers were studied. Nitrite and citrulline were measured in serum and urine
by spectrophotometry.Median serum nitrite and citrulline levels and urine
citrulline levels were higher among patients as compared with controls (p <
0.05). Patients with skin involvement stood out and had higher median serum and
urine citrulline levels (p < 0.05). Disease activity correlated with steroid
dosage, serum nitrite levels, and serum and urine citrulline levels (p < 0.05).
Steroid dosage correlated with serum citrulline level (p < 0.05). Serum and urine
citrulline levels correlated with each other (p < 0.01). In the subset of 13
individuals with renal involvement, serum and urine citrulline levels correlated
with each other (p < 0.01) as did urine nitrite and citrulline levels (p <
0.05).NO production is increased among patients with SLE, and this increase
correlates with disease activity and dosage of steroids used. The addition of a
urine test to measure NO production as a marker of disease activity using simple
spectrophotometry can be a valuable adjunct to other tests, can obviate the need
for drawing a blood sample for this purpose, and can be repeated as often as
necessary.
PMID- 17039083
TI - Early onset methotrexate-induced pancytopenia and response to G-CSF: a report of
two cases.
AB - Methotrexate (MTX) is one of the most widely used antirheumatic drugs for the
treatment of rheumatoid arthritis. Whereas the hepatotoxicity of methotrexate is
well recognized, the hematologic toxicity, namely, pancytopenia, is still a
concern and is potentially fatal. We report two cases of early-onset methotrexate
induced pancytopenia that were successfully treated with granulocyte colony
stimulating factor (G-CSF). The pancytopenia improved with 3 days of
administration. A review of the literature revealed at least 146 reported cases
of MTX-induced pancytopenia. Significant risk factors for myelotoxicity included
renal impairment, infection, and hypoalbuminemia. Successful management includes
prompt discontinuation of MTX, intravenous folinic acid, high-dose steroids and,
as in our case, G-CSF.
PMID- 17039084
TI - Pneumococcal pyomyositis: a patient with diagnostic problems and complications.
AB - Pyomyositis is an uncommon condition that may present a difficult problem in
diagnosis. We report the development of Streptococcus pneumoniae pyomyositis
involving the iliacus, iliopsoas, and gluteus muscles in a patient with elevated
serum levels of antinuclear and antiphospholipid antibodies but without clinical
evidence of connective tissue disease. Magnetic resonance imaging demonstrated
rapid evolution of the infection, with progression from muscle edema to abscess
formation over a period of 10 days. The diagnosis was initially missed, and
osteomyelitis and sacroiliitis developed. Pyomyositis should be suspected in
patients with the acute onset of severe, localized muscle pain and fever. As in
this case, failure to promptly diagnose and treat this infection can result in
significant morbidity.
PMID- 17039085
TI - Recurrent alveolar hemorrhage and pulmonary capillaritis in the "primary"
antiphospholipid syndrome.
AB - Pulmonary involvement in the primary antiphospholipid syndrome (PAPS) has
generally been on the basis of thromboembolism. We describe a patient with
hemorrhagic alveolitis, a life-threatening complication that must also be
considered. The patient was a 63-year-old Caucasian man who had a past history of
recurrent deep vein thromboses as well as an arterial occlusion of the left
popliteal artery and who developed hemorrhagic alveolitis and capillaritis at age
57 years, which was treated with long-term cyclophosphamide, steroids, and
anticoagulation. Four years later, he had a recurrence of the same condition, and
a positive lupus anticoagulant test was found. Severe thrombocytopenia, diagnosed
as idiopathic thrombocytopenic purpura, was treated with platelet transfusions
and increasing steroid dosage. Hemorrhagic adrenal infarction supervened at this
time, and a septicemic illness was treated with intravenous antibiotics. Diffuse
alveolar pulmonary hemorrhage is an unusual complication of the APS that is being
increasingly reported, and recognition of its possible fatal course is of great
importance for the treating physician. Severe thrombocytopenia that could
contribute to hemorrhage may also accompany the APS, but this is unusual.
PMID- 17039086
TI - Is Listeria monocytogenes an important pathogen for prosthetic joints?
AB - Listeria monocytogenes usually causes meningitis or bacteremia, often in
immunocompromised adults, pregnant women, or infants. We report a case of septic
arthritis caused by L. monocytogenes in a patient with seronegative rheumatoid
arthritis (RA) whose hip replacement was infected. She subsequently died,
probably secondary to an adult respiratory distress syndrome, a rare complication
of listerial infection. We also reviewed all 18 previously reported cases of
septic arthritis caused by L. monocytogenes. The frequency of underlying RA,
diabetes, neoplastic disease, and immunosuppressive therapy is prominent, as is
the concurrent presence of a previous knee or hip replacement. Thus, the
simultaneous presence of immune suppression and certain medical disorders or
their treatment and a prosthetic joint should alert the clinician to the
possibility that L. monocytogenes is the offending microbial agent. In contrast,
in immunocompetent persons the usual Gram-positive cocci such as staphylococci,
streptococci, or even pneumococci predominate. Although the outcome of
appropriate treatment with penicillin or ampicillin alone (or with an
aminoglycoside or trimethoprim/sulfamethoxazole in penicillin-allergic
individuals) is usually favorable, complicating medical disorders can lead to
death. Cephalosporins are rarely effective antimicrobial agents in patients with
listeriosis.
PMID- 17039087
TI - Postpartum multifocal avascular necrosis: what are the possible etiologies?
AB - Avascular necrosis of bone (osteonecrosis) that is atraumatic is most frequently
associated with corticosteroid excess or alcoholism and usually involves the
femoral head. We report a case of multifocal avascular necrosis in a 38-year-old
woman with autoimmune Addison's disease taking corticosteroid replacement
therapy. The onset of joint symptoms occurred 6 months after a pregnancy
complicated by acute fatty liver and disseminated intravascular coagulation.
Although both knees and ankles were involved, an unusual feature is that the hips
were spared. As illustrated in this patient, avascular necrosis is frequently
misdiagnosed in cases of joint pain of acute onset and may occur in the context
of physiologic replacement doses of corticosteroids. Etiologic factors can
precede the onset of symptoms and the diagnosis by several months.
PMID- 17039088
TI - Worsening of arthritis with antiretroviral therapy: the coexistence of rheumatoid
arthritis and human immunodeficiency virus infection revisited.
AB - The observation of remission occurring in several rheumatoid arthritis (RA)
patients who subsequently became infected with human immunodeficiency virus (HIV)
suggested that these diseases are mutually exclusive. Subsequent case reports of
progression of destructive rheumatoid arthritis, even with depleted CD4 cell
counts, seemed to imply that active RA may be independent of CD4 lymphocyte
number and function. We report an HIV-infected individual who developed
rheumatoid arthritis, which rapidly worsened with the initiation of
antiretroviral therapy. The worsening disease course correlated with the increase
in CD4 cell count and with the decrease in HIV viral load, perhaps suggesting a
central role for the CD4 cells in the pathogenesis of rheumatoid arthritis in
this particular patient. Among the therapeutic options to consider in such a
patient, indomethacin and hydroxychloroquine may offer additional benefit of
inhibiting viral replication. The cautious use of methotrexate with several
limitations is possible, although sulfasalazine (to which our patient responded)
may be a safer option.
PMID- 17039089
TI - Malignancies and autoimmune rheumatic diseases.
PMID- 17039090
TI - Improved lung function in patients with scleroderma and interstitial disease with
the use of cyclophosphamide.
PMID- 17039091
TI - Practice tip 15. Prevention of inframammary moniliasis.
PMID- 17039092
TI - Atypical Behcet's disease with peripheral erosive arthopathy.
PMID- 17039093
TI - Serum leptin levels in patients with rheumatoid arthritis.
PMID- 17039094
TI - Mondor's disease and polymyalgia rheumatica: a case report.
PMID- 17039095
TI - Finessing fibromyalgia.
PMID- 17039097
TI - Crohn's disease arthritis treated with infliximab: an open trial in four
patients.
AB - Four patients with Crohn's disease arthritis, who were unresponsive to
conventional treatment, improved very rapidly and safely with the use of
infliximab, the chimeric antibody directed against tumor necrosis factor alpha.
The patients were able to stop or significantly decrease other antirheumatic
medications after the infliximab infusions. It is likely that tumor necrosis
factor plays a major role in the arthritis as well as the bowel involvement that
is seen in Crohn's disease. Suppression of this cytokine may effectively
ameliorate Crohn's disease arthritis in some patients.
PMID- 17039098
TI - The treatment of fibromyalgia with cranial electrotherapy stimulation.
AB - In cranial electrotherapy stimulation (CES), micro-current levels of electrical
stimulation are passed across the head via electrodes clipped to the ear lobes.
After successful clinical use of CES with fibromyalgia patients in our clinic, it
was decided to test these results with a double-blind, placebo-controlled study
in which 60 randomly assigned patients were given 3 weeks of 1-hour-daily CES
treatments, sham CES treatments, or were held as wait-in-line controls for any
placebo effect in the sham-treated patients. Treated patients showed a 28%
improvement in tender point scores, and a 27% improvement in self-rated scores of
general pain level. The number of subjects rating their quality of sleep as poor
dropped from 60% at the beginning of the study to 5%. In addition, there were
significant gains in the self-rated feelings of well-being and quality of life,
plus gains in six stress-related psychological test measures. No placebo effect
was found among the sham-treated controls. A theoretical role of CES in affecting
the brain's pain message mechanisms and/or neurohormonal control systems is
discussed. It is concluded that CES is as effective as the drug therapies in
several trials, with no negative side effects, and deserves further consideration
as an additional agent for the treatment of fibromyalgia.
PMID- 17039100
TI - Dissection of the temporal artery in a patient with giant cell arteritis.
AB - A 74-year-old woman presented to her rheumatologist with classic symptoms of
giant cell arteritis. The temporal arteries were strikingly swollen, warm, and
erythematous. On biopsy of the right temporal artery, a focal dissection was
found associated with a pan-arteritis and giant cells. Isolated temporal artery
dissection in giant cell arteritis has not been reported previously. We propose
that the unusually intense vascular inflammation may have weakened the vessel
wall, so that the dissection occurred during the routine physical exam or biopsy.
We believe this case illustrates that physicians should take special care in the
examination of floridly inflamed vessels, because vigorous palpation might lead
to dissection. In the case of patients with giant cell arteritis, dissection may
result in an increased risk of ischemic complications, such as scalp necrosis.
PMID- 17039101
TI - Salmonella group D septic arthritis and necrotizing fasciitis in a patient with
rheumatoid arthritis and diabetes mellitus.
AB - Necrotizing fasciitis is an uncommon manifestation of Salmonella infection. We
report a case of Salmonella group D septic arthritis complicated with necrotizing
fasciitis in a 51-year-old man who had noninsulin dependent diabetes mellitus and
rheumatoid arthritis. He presented with fever and severe right hip pain
complicated with septic shock and disseminated intravascular coagulation.
Crepitation was noticed upon physical examination, and plain films showed
numerous air bubbles in the soft tissue around the hip joint. Prompt antibiotic
therapy and surgical management were performed with a successful response. The
causative organism was Salmonella group D. Antibiotic was given in the total
course of 3 months, and there was no relapse of salmonellosis after 2 years
follow up. The differential diagnosis of causes of non-clostridial crepitant soft
tissue and muscle infections must include Salmonella, especially in patients who
have underlying diseases or are taking immunosuppressive drugs. Prompt management
is needed to reduce mortality and morbidity. Long-term suppressive therapy may be
needed to prevent relapse.
PMID- 17039102
TI - Spontaneous abdominal hemorrhage with AA-amyloidosis and vasculitis in a patient
with rheumatoid arthritis.
AB - Both rheumatoid vasculitis and amyloidosis in rheumatoid arthritis (RA) are
uncommon. We describe a patient in whom they occurred together and were
associated with fatal intra-abdominal hemorrhage. A 56-year-old Caucasian woman
was referred because of increasing lethargy, edema, and proteinuria. She had
suffered from seropositive, erosive, nodular RA for 14 years. Previously, she had
undergone numerous joint replacements, a thyroidectomy for amyloid-associated
(AA) amyloidosis of the thyroid that caused a large goiter and a renal biopsy
that showed renal AA-amyloidosis in the context of nephrotic syndrome. As her
condition deteriorated, this patient became increasingly reluctant to go to the
hospital and to take drugs beyond analgesics. Thus, her RA was chronically under
treated. While in the hospital for evaluation, this patient suddenly developed
hypotension, tachycardia, and a severe colicky left-sided abdominal pain
radiating from the left upper quadrant/epigastric region to the left iliac fossa.
Computed tomography (CT) showed a large amount of echogenic free fluid within the
abdomen and marked thickening of the omentum. At laparotomy, 2 liters of free
blood was found adjacent to a hematoma of the greater omentum, and it was
evacuated without identification of a discrete bleeding point. All solid and
hollow organs were normal. The omentum was noted to be very friable. She
developed a more disseminated bleeding diathesis and persistent peritoneal
hemorrhage via her abdominal drains. She succumbed shortly afterward. Histology
revealed extensive omental hemorrhage and one large vessel within the area of
hemorrhage showed a severe necrotizing vasculitis. Extensive amyloid deposition
was also found within the walls of the smaller omental arterioles. Vasculitis in
the context of RA is relatively rare and is associated with under treated,
seropositive disease. Skin and nerve involvement are most common, but bowel
involvement has been reported, with a highly significant morbidity (partly due to
late presentation/recognition). Similarly, AA-amyloidosis is a rare but feared
long-term concomitant of under treated RA. Early recognition can permit
successful anti-inflammatory therapy to affect a clinical and pathological
remission; continued inflammatory stimulation is associated with rapid
progression and demise. Chronically under treated patients with RA are more prone
to rare but potentially devastating complications. Gastrointestinal catastrophes
are a feature of both rheumatoid vasculitis and of amyloidosis, here uniquely co
localized.
PMID- 17039103
TI - Wegener's granulomatosis presenting as subglottic stenosis.
AB - Wegener's granulomatosis is an uncommon disease process that causes necrotizing
vasculitis predominantly in the lungs, kidneys, and upper air-ways. Subglottic
stenosis has been observed in up to 20% of patients with established diagnosis of
Wegener's granulomatosis, but it is rarely the initial manifestation of the
disease. This case report presents a patient with Wegener's granulomatosis who
had subglottic stenosis as predominant initial manifestation, without signs of
lung or kidney involvement. The diagnosis was unclear initially due to the
absence of damage to these organs and to the nonspecificity of the initial biopsy
findings. After stabilizing the patient, an elevated cytoplasmic pattern of
antineutrophil cytoplasmic antibodies titer was obtained, which played an
important role in the diagnostic process and led to a second biopsy that showed
vasculitis. The patient had an excellent response to prednisone, methotrexate,
and trimethoprim/sulfamethoxazole, but as with many such cases, she also required
tracheo-laryngoplasty.
PMID- 17039104
TI - Cardiac tamponade: a life-threatening complication of Still's disease.
AB - Pericarditis, a common feature of adult-onset and juvenile-onset Still's disease,
is rarely complicated by cardiac tamponade. We report one patient with juvenile
onset and another with adult-onset Still's disease presenting with pericardial
tamponade. On the basis of our experience and analysis of literature, we suggest
early identification of pericarditis and the life-threatening complication of
tamponade, with institution of aggressive intervention with corticosteroids and,
if necessary, pericardiocentesis and pericardial window formation. These cases
remind physicians about the need to include Still's disease in the differential
diagnosis of pericarditis and tamponade and to not neglect the potential of
severe systemic inflammation to lead to fatal complications in this group of
patients.
PMID- 17039105
TI - Ticlopidine-induced lupus.
AB - Ticlopidine is a widely used drug for prevention of stroke and other serious
vascular events with a multitude of possible side effects. An increasing number
of drugs are being recognized as the triggering agents of drug-induced lupus. We
describe three patients in whom the etiologic connection between ticlopidine and
lupus was supported by the appearance of lupus-like features (fever, rash,
arthritis, renal involvement, positive antinuclear and antihistone antibodies),
shortly after drug initiation, and their gradual resolution after its
discontinuation. If suggested by clinical or/and laboratory findings (fever of
unknown cause, musculoskeletal involvement, hematologic abnormalities), the
possibility of ticlopidine-induced lupus should be taken into consideration and
appropriate investigations should be performed. Patients should resolve slowly
but completely after withdrawal of ticlopidine.
PMID- 17039106
TI - Thrombotic thrombocytopenia purpura in a patient with systemic sclerosis.
AB - Thrombotic thrombocytopenic purpura (TTP) has been associated with scleroderma
renal crises (SRC) in the past. However such reports markedly diminished after
the onset of ACE inhibitor use. Recently, reports again have surfaced that
describe scleroderma patients presenting with clinical evidence of TTP. We
describe a 50-year-old female with longstanding limited cutaneous scleroderma who
presented with hematochezia and thrombocytopenia along with other findings
suggesting TTP. A colon biopsy revealed thrombi within the lumen. Her course was
complicated by renal failure and hypertension that did not respond to ACE
inhibitor therapy alone. She improved after a course of plasma exchange. She was
discharged home only to return 2 months later with grand mal seizures and
hypertension. During her course she developed adult respiratory distress
syndrome. She again responded to plasma exchange and she was discharged home. She
has remained stable for 2 years. This report emphasizes the importance of fully
evaluating patients with longstanding limited cutaneous scleroderma who present
with renal failure, hypertension, and thrombocytopenia in association with
multiorgan complications. All possible etiologies, including SRC, TTP,
vasculitis, and sepsis should be considered. Tissue biopsies (in this case, a
colon biopsy revealed thrombi within the vessel lumen) may prove beneficial in
assisting with the diagnosis. For such patients who fail treatment with ACE
inhibitors, plasma exchange may be considered.
PMID- 17039107
TI - Hip pain as the presenting manifestation of acute gouty sacroiliitis.
AB - Gout can present in a variety of less typical forms. We describe a case of an
elderly woman presenting with hip and lower extremity pain. It remained
undiagnosed for several days but proved to be secondary to gouty involvement of
the right sacroiliac (SI) joint. Monosodium urate crystals were identified in
computed tomographic guided aspiration of the SI joint. The importance of
obtaining a good history and performing a complete physical examination if the
diagnosis of sacroiliitis (or any other musculoskeletal disorder) is to be made,
its cause defined, and proper treatment instituted is emphasized.
PMID- 17039109
TI - Treatment of rheumatic disease by tumor necrosis factor-alpha blockade: knowns
and unknowns.
PMID- 17039108
TI - Alveolar hemorrhage and pulmonary hypertension in systemic sclerosis: a continuum
of scleroderma renal crisis?
AB - Alveolar hemorrhage occurs as a complication of systemic inflammatory diseases.
In addition to alveolar hemorrhage, patients with systemic sclerosis (SSc) may
suffer from digital infarction, pulmonary hypertension, and renal crisis.
Although a common pathogenesis of this disease that explains the variety of
problems during a patient's illness has yet to be identified, the unique
characteristics of SSc may alter our approach to alveolar hemorrhage in this
patient population. We describe a patient with SSc, who presented with pulmonary
hypertension and alveolar hemorrhage complicated by features suggesting re
occurrence of scleroderma renal crisis. Our successful management of this
patient, with complications that are usually of high morbidity, may be attributed
to our judicious use of glucocorticosteroid therapy and maximization of
angiotensin-converting enzyme inhibition. In view of the potential for
glucocorticoids to precipitate scleroderma renal crisis, we suggest caution in
the use of these medications for manifestations that may be similar in their
pathogenesis.
PMID- 17039110
TI - Dermatology vignette. Pseudoporphyria caused by NSAIDs.
PMID- 17039111
TI - Practice tips. Treatment of chronic thoracic pain with interscapular weights.
PMID- 17039112
TI - Comments regarding Hans Reiter's role in Nazi Germany.
PMID- 17039114
TI - Can drug-induced lupus cause aortic aneurysm?
PMID- 17039115
TI - A case of mixed connective tissue disease with cystic pancreatitis: successful
treatment by cyclophosphamide.
PMID- 17039116
TI - Celecoxib and rofecoxib: a distinction with a difference?
PMID- 17039117
TI - Spin doctors.
PMID- 17039119
TI - Systemic lupus erythematosus in men: a retrospective analysis in a Veterans
Administration Healthcare System population.
AB - Systemic lupus erythematosus (SLE), a connective tissue disease of unknown
etiology, is generally considered to occur in women of child-bearing age and to
be uncommon among men . Because of the female predominance in most studies, less
is known about the disease in men. To begin to better understand lupus in men, we
retrospectively analyzed all the SLE patients from all the hospitals in the
Department of Veterans Affairs (VA) system, a population that is predominantly
male. Between 1987 and 1996, 2614 SLE patients were retrieved from the VA
databank; 2144 were male, making this the largest group of male patients with SLE
reported in United States of America. Age, racial and geographic distribution,
comorbidities, and mortality of the SLE patients are reported. This study
suggests that SLE men in this population are older at onset of disease, have
different comorbidities, and have a higher mortality at 1 year than women with
SLE. These findings suggest that men with SLE have a more complex clinical course
than women, although the data do not illuminate whether the comorbidities are due
to or coincident with SLE. On the basis of these data, practitioners are reminded
to consider SLE in the differential diagnosis for older men and be attentive to
the frequent presence of comorbidities such as cardiac ischemia and neoplasms.
Because of the identified regional variations in demographics, comorbidities, and
mortality, this study suggests the need for future SLE studies to include data
from multiple geographic areas.
PMID- 17039120
TI - COX-2 specific inhibitors in the management of osteoarthritis of the knee: a
placebo-controlled, randomized, double-blind study.
AB - COX-2 specific inhibitors have demonstrated significant safety advantages and
comparable efficacy in osteoarthritis (OA) compared with conventional
nonsteroidal anti-inflammatory drugs (NSAIDs), but no direct comparative trials
between COX-2 specific inhibitors have been published. In this double-blind,
placebo-controlled, parallel group, multicenter study, 182 patients (> or =40
years old) with OA of the knee were randomly assigned to treatment with celecoxib
200 mg q.d. (n = 63), rofecoxib 25 mg q.d. (n = 59), or placebo (n = 60) for 6
weeks. Arthritis assessments were performed at baseline and Weeks 3 and 6, or at
early termination. At Week 6, celecoxib and rofecoxib treatment resulted in
similar mean changes from baseline (p > 0.55) in arthritis pain visual analogue
scale, patient's global assessment, and total score for WOMAC; all changes were
superior to placebo (p < 0.05). In the patient's global assessment of arthritis
pain at Week 6, 79% of celecoxib-treated and 78% of rofecoxib-treated patients
improved by > or =1 grade, compared with 50% of placebo patients (celecoxib, p =
0.025; rofecoxib, p = 0.020). Adverse event incidences were similar among the
active comparators; however, celecoxib-treated patients had significantly fewer
adverse gastrointestinal symptoms compared with rofecoxib-treated patients, which
suggests that celecoxib may have a better gastrointestinal tolerability profile
than rofecoxib at these doses. Adverse events that prompted withdrawal occurred
in fewer than 7% of patients, and the overall incidences were similar between the
active agents. Once-daily doses of celecoxib 200 mg and rofecoxib 25 mg offer
comparable efficacy and are an effective alternative to conventional NSAIDs in
the management of OA.
PMID- 17039121
TI - The long-term use of azathioprine in patients with psoriatic arthritis.
AB - Despite the widespread use of methotrexate in the treatment of psoriatic
arthritis (PsA), there are patients who are either refractory, develop toxicity
to, or refuse to take methotrexate. In search of an alternative, we studied long
term tolerability of and clinical response to azathioprine (AZA) in PsA patients
in comparison with matched controls and followed them in a longitudinal clinic.
Twenty-eight of 485 patients followed prospectively between 1978 and 1998 took
AZA during their clinic follow-ups. Eighteen of the 28 took AZA for 12 months and
were included in the study. AZA was well tolerated by most patients, even in the
long-term. Although there was no statistically significant difference in the
reduction in number of actively inflamed joints between AZA-treated patients and
controls, and AZA was no better in preventing progression of damage, AZA was
still as good as the other medications. Consequently, AZA was often given to
individuals who had not responded to other medications in the past. We provide
illustrative case reports in which AZA also controlled psoriasis, and we conclude
that, whereas AZA is not superior to other medications in the treatment of PsA,
it may be safely used and it provides an alternative therapy for patients with
PsA.
PMID- 17039122
TI - Exocrine dysfunction of the pancreas in patients with chronic polyarthritis.
AB - We studied the extent to which exocrine dysfunction of the pancreas is seen among
patients with severe chronic polyarthritis and whether it might account for some
gastrointestinal symptoms. Our series consisted of 50 such chronic polyarthritis
cases; most had rheumatoid arthritis but had neither diagnosed or suspected
pancreatitis nor primary Sjogren's syndrome. They were asked about
gastrointestinal (GI) and sicca symptoms. The exocrine function of each pancreas
was evaluated by the fecal elastase-1-enzyme test. Thirty-two patients had GI
symptoms at least weekly. Forty had sicca eye syndrome and 26 had dry mouth.
There were two cases (4%; 95% confidence interval, 1-14%) with abnormally low
fecal elastase-1-enzyme test level. Chronic GI and sicca symptoms are frequent
among patients with severe chronic polyarthritis. Secondary Sjogren's syndrome
may cause exocrine insufficiency in the pancreas. That circumstance was not
common here, but it is worth remembering because it can be diagnosed by a
noninvasive method, and enzyme preparation treatment is available for the
symptoms, especially for postprandial pain and distention of the stomach.
PMID- 17039123
TI - Propylthiouracil-induced microscopic polyangiitis.
AB - The use of propylthiouracil (PTU) has been associated with various forms of
vasculitis. We herein describe the case of a patient with Grave's disease who,
after years of PTU therapy, developed a necrotizing vasculitis with anti-serine
protease-3 antibodies. Despite treatment with corticosteroids and
cyclophosphamide, the patient died of intra-alveolar hemorrhage secondary to her
vasculitis. Based on the vessel size involved, the organ distribution of
pathologic findings, and lack of granulomas, autopsy findings were felt to be
more consistent with microscopic polyangiitis (MPA) than with her original
clinical diagnosis of Wegener's granulomatosis. Her case satisfied both clinical
and pathologic criteria for MPA. An MPA diagnosis is important to consider in
similar clinical presentations because therapy may just need to be early
withdrawal of an inciting drug, such as PTU, and the initiation of
corticosteroids without cytotoxic therapy.
PMID- 17039124
TI - Corticosteroid-sparing effect of etanercept in idiopathic panuveitis resistant to
immunosuppressive therapy.
AB - Uveitis, an inflammatory eye disease with varying immunopathogenic mechanisms,
may be associated with autoimmune disorders, may be secondary to infection, or
may be idiopathic. Response to treatment of uveitis is inconsistent. In this
report we describe an adult with idiopathic panuveitis who attempted to lower his
oral corticosteroid dose from intolerable levels but was unable to do so because
of the reappearance of symptoms. His 8-year course was managed with ocular and
systemic corticosteroids, methotrexate, and cyclosporine, which allowed only
partially successful control of his ocular inflammation. Complete control was not
achieved until the addition of etanercept. With this case report we are the first
to describe the complete response of idiopathic panuveitis to etanercept. Our
success with this patient strongly supports the critical role of tumor necrosis
factor in the immunopathogenesis of some cases of idiopathic panuveitis.
Furthermore, etanercept offers a relatively nontoxic, safe option in cases of
panuveitis that are unresponsive to traditional immunosuppressive therapy.
PMID- 17039125
TI - HELLP-like syndrome associated with hepatic necrosis in a patient with systemic
lupus erythematosus.
AB - Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is often
associated with preeclampsia or hypertension in pregnancy. Pregnancy in patients
with systemic lupus erythematosus (SLE) may be complicated by development of a
lupus flare with thrombocytopenia, hypertension and renal insufficiency, which
may be difficult to distinguish from preeclampsia. We describe a 20-year-old
patient with SLE and anticardiolipin antibodies who developed a HELLP-like
syndrome during 2 successive pregnancies without the more typical symptoms of
preeclampsia or hypertension. This unusual presentation of HELLP syndrome during
pregnancy in a patient with SLE was evidenced by hematologic and liver enzyme
abnormalities as a sign of ongoing hepatic necrosis. Early recognition of this
syndrome is important because it may result in rapid deterioration with
progressive hepatic necrosis that can be reversible with early termination of
pregnancy.
PMID- 17039126
TI - Questioning the sensitivity of magnetic resonance imaging in early septic
spondylodiscitis.
AB - Septic spondylodiscitis is an uncommon disease, but one with serious
complications and potentially high morbidity and mortality. The diagnosis is
sometimes delayed, particularly in those patients with an insidious mode of onset
and nonspecific symptoms. Several imaging methods are available to facilitate the
early diagnosis of septic spondylodiscitis, and of these methods magnetic
resonance imaging (MRI) has been reported to be the most sensitive, revealing
abnormalities earlier than plain x-ray, gallium scan and bone scan. We report a
case of septic spondylodiscitis in which MRI did not demonstrate evidence of
discitis after a symptom period of seven days. The diagnosis was later confirmed
by bone scan and repeat MRI. We suggest that a negative or equivocal MRI cannot
exclude infective spondylodiscitis, especially in the early stages of the disease
process. In such cases, it is important to note that the addition of a short tau
inversion recovery sequence will increase the sensitivity of MRI, and,
additionally, gadolinium should be administered if the magnetic resonance study
is negative and a strong clinical suspicion of spondylodiscitis exists.
PMID- 17039127
TI - Successful pamidronate treatment of severe and refractory regional migratory
osteoporosis.
AB - We report the case of a middle-aged patient with repeated attacks of regional
migratory osteoporosis of the lower limbs, manifesting as severe pain and
swelling of both joint and periarticular areas, and marked physical disability
during a period of 2 1/2 years. After the therapeutic failure of conservative
therapy (physical therapy, rehabilitation therapy, analgesics and nonsteroidal
anti-inflammatory drugs (NSAIDs)) and after the correct diagnosis was reached,
pamidronate treatment was instituted. The results were a rapid, complete, and
long-lasting remission of the symptoms and the renewal of the patient's previous
activities. Intravenous biphosphates are proposed as a safe and promising therapy
for regional migratory osteoporosis. To our knowledge, this is the first report
of pamidronate treatment for this condition.
PMID- 17039128
TI - Amyopathic dermatomyositis in children: a diagnostic and therapeutic dilemma.
AB - Juvenile dermatomyositis is an inflammatory disease of unknown etiology that
primarily affects skin and muscles. The pathognomonic Gottron's sign consists of
symmetric macules and papules on the dorsal aspect of the interphalangeal joints
and exterior areas of the big joints. A periorbital violaceous (heliotrope) skin
rash is also characteristic. There may be a discordance in time of presentation
of the skin and muscle disease, and a small subset of patients apparently do not
develop muscle disease at all. The absence of muscle involvement is termed
'amyopathic dermatomyositis.'We describe two children who presented with the
characteristic rash of juvenile dermatomyositis but with no clinical evidence of
muscle involvement. One developed muscle weakness 3 years later. Neither patient
had a full muscle work-up at the onset of the disease, which left questions about
diagnoses and whether or not there may have been subtle muscle involvement. On
the basis of our literature review, the outcome of these patients is uncertain,
although it appears that myositis develops in many, maybe most, affected
children. We suggest that in the absence of muscle disease, application of
sunscreen and administration of hydroxychloroquine sulfate may ameliorate the
rash. More aggressive treatment will need to be given when muscle involvement can
be demonstrated.
PMID- 17039129
TI - Kawasaki syndrome in an adult: case report and review of the literature in
adolescents and adults.
AB - Kawasaki syndrome in adults is very rare, with fewer than 50 cases reported in
the English-language literature. We describe the case of a physician with
Kawasaki syndrome and summarize the clinical features and treatment of 11
patients in the literature since the last review in 1994. Our patient presented
with high fever, conjunctivitis, and arthralgias, then developed progressive
toxicity with oral lesions, cervical adenopathy, and desquamation of the fingers
and toes. No exanthematous rash or coronary artery aneurysms were found. Recovery
was rapid after therapy with aspirin and intravenous immunoglobulin (IVIg). The
diagnosis of Kawasaki syndrome depends on clinical criteria and the exclusion of
other diseases. This diagnosis can be challenging to make in an adult,
particularly when it presents without all typical features. Kawasaki syndrome
must be considered nonetheless in an adult with unexplained fever of more than 5
days duration, because early diagnosis and combination therapy with aspirin and
IVIg can prevent the life-threatening complication of coronary artery aneurysms.
PMID- 17039132
TI - Baker cyst calcifications in a patient with rheumatoid arthritis.
PMID- 17039130
TI - Periostalgia pubis: a cause of chronic abdominal pain.
AB - Periostitis pubis has been proposed as a new clinical entity, one characterized
by abdominal pain and tenderness over the os pubis. Periostitis pubis, as defined
by Rubenstein , is inflammation at the insertion point of the anterior abdominal
musculature onto the periosteum of the os pubis. A case is described in which the
patient underwent multiple invasive diagnostic procedures before seeking help at
the author's medical facility with a clinical problem similar to periostitis
pubis. Her pain was completely relieved by infiltration of the tender superior
surface of the os pubis. It is suggested that a more appropriate term for this
problem may be 'periostalgia pubis. As no evidence exists that inflammation is
involved in the pathophysiology, the primary goal of this case description is to
promote recognition of the disorder which is probably under reported. It is hoped
that recognition will lead to further information regarding the natural history
and prevalence of the disorder.
PMID- 17039133
TI - Practice tips. 17. Minimizing falls while bathing.
PMID- 17039134
TI - Thoughts on Japanese versus North American rheumatology.
PMID- 17039135
TI - Of skin and bones.
PMID- 17039137
TI - Metal sensitivity in patients with orthopedic implants.
PMID- 17039136
TI - Psoriatic arthritis, methotrexate, and liver toxicity.
PMID- 17039138
TI - Weight loss and exercise walking reduce pain and improve physical functioning in
overweight postmenopausal women with knee osteoarthritis.
AB - We conducted an uncontrolled pilot study to determine the effects of a weight
loss and walking program on knee pain and physical function in overweight and
obese (body mass index; BMI [kg/m] 25-29.9 and BMI > or = 30, respectively)
postmenopausal women with knee osteoarthritis (OA). Forty-eight such women
completed self-report (Western Ontario and McMaster University Osteoarthritis
Index (WOMAC)) and performance-based measures of physical function ("up and go"
test, 6-min walk) and enrolled in a 6-month intervention that included weekly
nutrition classes and an exercise-walking program. The intervention produced an
average weight loss of 5.6 +/- 4.0 kg in the 30 women who completed the program.
There also were significant improvements in the 6-min walk and on VO(2max).
Improvements in the timed up and go test and on the WOMAC pain and function
scores, however, were restricted only to women who were classified as obese at
baseline. These findings suggest that a 6-month weight loss and walking program
improves measures of physical functioning and pain in overweight and obese
postmenopausal women with knee OA. Among obese women, functional improvement
correlated with weight loss, encouraging continued emphasis on weight loss for
managing knee OA.
PMID- 17039139
TI - Liver biopsy in psoriatic arthritis to detect methotrexate hepatotoxicity.
AB - The use of methotrexate in the treatment of psoriatic arthritis is associated
with risk of hepatotoxicity. However, monitoring of liver-associated enzymes
often lacks sensitivity, and guidelines for serial liver biopsies in psoriatic
arthritis are not yet well established. We performed a retrospective review of
all patients with psoriatic arthritis receiving methotrexate who were enrolled in
the disease-modifying anti-rheumatic drug clinics (DMARD clinics) at the Air
Force and Army hospitals in San Antonio, Texas. Information was obtained
regarding methotrexate regimen, liver-associated enzyme results, and liver biopsy
results. Thirty psoriatic arthritis patients were taking methotrexate in the
DMARD clinics. Seventeen patients had a total of 21 biopsies. Biopsies were
performed for surveillance dictated by cumulative dose. Liver biopsies were
graded on Roenigk scale of I-IV where I is mild steatosis, II is moderate
steatosis, IIIa is mild fibrosis, IIIb is severe fibrosis, and IV is cirrhosis.
Ten biopsies were grade I, 5 were grade II, 5 were grade IIIa, 1 was grade IIIb,
and none were grade IV. In this very small retrospective study, regular
monitoring of liver-associated enzymes did not correlate with histologic
deterioration in our patients. Until prospective studies are performed, we
suggest that routine liver biopsies are necessary to monitor for methotrexate
hepatotoxicity in psoriatic arthritis.
PMID- 17039140
TI - Skeletal manifestations of leprosy: analysis of 137 patients from different
clinical settings in the pre- and post-modern treatment eras.
AB - This study was conducted to further characterize the nature of leprosy-related
bone alterations, to develop a hypothesis of their pathophysiology, and to define
the impact of treatment on bone damage. Radiographs of 60 patients under care at
the Carville, Louisiana leprosy hospital were compared with 50 from the early
(before availability of effective treatment) part of this century and with 27
from the Toronto (Ontario, Canada) leprosy clinic. Two-thirds of lesions were so
severe that distal digital tufts had been lost to whittling, resorption, or
fragmentation. Fifty percent were felt to be pathognomonic for the changes of
leprosy. Resorption, fragmentation, and malaligned fractures are highly
suggestive of leprosy, while diaphyseal whittling appears specific when medullary
sclerosis or wavy diaphyseal borders are present. Medicinal intervention appeared
to be of limited benefit for bone damage; perhaps greater attention to joint/bone
protection (as recommended in diabetes management) will prove helpful.
Environmental adjustment to minimize injury risk and daily limb examination for
injury are recommended.
PMID- 17039141
TI - Vasculitis following treatment of rheumatoid arthritis with extracorporeal
staphylococcal protein a immunoadsorption column (prosorba).
AB - We report a case of vasculitis after Prosorba treatment in a patient with
rheumatoid arthritis. The patient is a 66-year-old white male with long standing
rheumatoid arthritis and hepatitis B. He was treated with the standard regimen
for Prosorba treatment. He improved and met criteria for an American College of
Rheumatology (ACR) 20% response. While on therapy he developed a nonhealing
ulcer. Approximately 2 weeks after treatment was completed, he developed palpable
purpura and mononeuritis multiplex. Deep dermal biopsy confirmed the presence of
both small and medium vessel vasculitis. Nerve conductions studies were
consistent with neuropathic conduction delays. He was treated with 1mg/kg/day of
oral prednisone. Prosorba has been reported to cause leukocytoclastic vasculitis
during treatment, but has not been noted to involve medium sized vessels. This
patient's history and presentation are most consistent with rheumatoid arthritis
associated vasculitis, though the Prosorba treatment cannot be ruled out as a
cause or a contributing factor. Importantly, although Prosorba treated his
synovitis, it did not prevent concomitant vasculitis.
PMID- 17039142
TI - Septic arthritis caused by Burkholderia pseudomallei: case report and review of
the literature.
AB - We describe a case of septic arthritis and bacteremia caused by Burkholderia
pseudomallei, a bacterium that is endemic in East Asia and northern Australia. We
believe that dissemination occurred in our patient after surgical excision of a
pulmonary nodule. Bacteremic melioidosis can present with musculoskeletal
involvement in 2-10% of patients, but septic arthritis is uncommon. A review of
the literature shows a total of 66 patients reported with septic arthritis caused
by this organism. Patients with septic arthritis caused by Burkholderia
pseudomallei were likely to have diabetes mellitus, and the knee is the joint
most frequently affected by this organism. Recommended initial treatment consists
of ceftazidime, alone or in combination with trimethoprim/sulfamethoxazole, high
dose imipenem/cilastatin, or high dose cefoperazone/sulbactam. This is followed
by a 12-20 week course of oral therapy (based on susceptibilities) to eradicate
the organism. Most patients with subacute or latent disease do well after full
antibiotic treatment, but relapses are common if full treatment is not given.
Awareness of this disease is important even in areas outside of Asia given the
increasing frequency of international travel and the growing likelihood of
imported cases, along with an aging population of Vietnam veterans and
immigrants.
PMID- 17039143
TI - Alveolar echinococcosis of the spine.
AB - Alveolar echinococcosis (AE) is a rare parasitic disease caused by the larval
stage of Echinococcus multilocularis. It differs from cystic echinococcosis
caused by Echinococcus granulosus. The main endemic areas of AE are Alaska,
Canada, Japan, and parts of Europe. Hepatic involvement invariably occurs, but it
is unusual for bone to be affected. We report the case of a woman presenting with
a long history of pain, cachexia, morning stiffness, and biological signs of
inflammation. Radiographs and principally magnetic resonance images were
nonspecific, showing inhomogeneous osteolysis of vertebral bodies without loss of
intervertebral disc height but with a paravertebral mass. The diagnosis
ultimately relied on pathological examination, which showed an anhistic laminated
membrane colored in red with Periodic-Acid-Schiff surrounding a central cavity,
and by the serologic testing, principally ELISA Em2(+) method, which allowed a
97% specificity and 99% specificity in the diagnosis of AE. AE involving bone is
an uncommon condition. Although magnetic resonance imaging can be used to search
for local complications, the features it detects are, like those revealed by
radiographs, nonspecific and can lead to AE being misdiagnosed as neoplasm or
tuberculous osteitis. When a patient presents with suspected AE in an endemic
area, the diagnosis can be achieved by serological testing alone (Western blot
and Em2(+) ELISA), thereby avoiding the need for biopsy.
PMID- 17039144
TI - Worsening of macrophage activation syndrome in a patient with adult onset Still's
disease after initiation of etanercept therapy.
AB - The macrophage activation syndrome (MAS) is a rare, potentially fatal, clinical
syndrome, which has been described in childhood rheumatic disorders. MAS is
defined by a prolonged period of fevers, pancytopenia, and hypertriglyceridemia
(with or without hypofibrinogenemia). Histopathological examination of bone
marrow, spleen, or lymph nodes shows hemophagocytosis by mononuclear phagocytes.
In patients with Still's disease, observed triggering events for MAS have
included both infectious processes and pharmacological agents, such as parenteral
gold and nonsteroidal anti-inflammatory drugs. We report the case of a young
woman with adult-onset Still's disease (AOSD), complicated by an Epstein-Barr
virus infection and subsequent MAS, whose course worsened after administration of
the soluble tumor necrosis factor-alpha receptor, etanercept. Subsequent
treatment with pulse corticosteroids and cyclosporine A induced a dramatic
clinical improvement. Treatment data regarding the use of etanercept in AOSD are
lacking; given our experience and recent reports in children with Still's
disease, we would suggest caution using this agent in patients with AOSD,
particularly when complicated by MAS.
PMID- 17039145
TI - Acute synovitis, fever and rash possibly caused by metallic debris from a
loosened knee prosthesis in a patient with rheumatoid arthritis.
AB - A 39-year-old woman with long-standing seropositive rheumatoid arthritis who had
a total replacement of her left knee with a modular prosthesis in 1994 presented
with fever, pruritic rash, and acute synovitis of that joint following local
trauma. Synovial fluid showed a charcoal-like color, and contained abundant
phagocytes laden with metal particles. In patients with rheumatoid arthritis who
have undergone total joint replacement, metal particle reactions and possible
hyper-sensitivity should be added to the list of potential causes of superimposed
acute synovitis and systemic manifestations.
PMID- 17039146
TI - Polymyalgia rheumatica and temporal arteritis with sacroiliitis and osteitis
pubis.
AB - Polymyalgia rheumatica (PMR) and temporal arteritis (TA) have been associated
with a seronegative polyarthritis that can mimic rheumatoid arthritis.
Sacroiliitis and osteitis pubis are most often encountered in the different types
of spondyloarthropathy. However, sacroiliitis and osteitis pubis have rarely been
described in patients with polymyalgia rheumatica and temporal arteritis. We
present two patients, one with temporal arteritis and the other with polymyalgia
rheumatica, who also had many features of a spondyloarthropathy, including
sacroiliitis and osteitis pubis. In reviewing the literature, we found 30 other
patients with a diagnosis of PMR who also had sacroiliitis and/or osteitis pubis.
We propose that the inflammatory arthritis associated with polymyalgia rheumatica
and temporal arteritis can involve the axial joints, resembling a
spondyloarthropathy. It is important for the clinician to recognize that
sacroiliitis and osteitis pubis have been associated with PMR and TA so that
their radiographic presence does not dissuade the clinician from making the
correct diagnosis.
PMID- 17039147
TI - Pyogenic arthritis caused by capnocytophaga gingivalis in an immunocompetent
three-year-old male.
AB - Capnocytophaga gingivalis is most often isolated as normal oral flora or with
periodontal disease. This organism is also associated with sepsis usually in
immunocompromised hosts. We identified pyogenic arthritis caused by C. gingivalis
in a 3-year-old immunocompetent male, whose clinical course closely resembled
monoarticular onset pauciarticular juvenile rheumatoid arthritis. This is the
first report of C. gingivalis septic arthritis in the world literature, but there
are increasing reports of infections with this carbon dioxide-loving organism at
other sites in non-immunocompromised individuals. The subacute presentation of
the monoarthritis with this organism of low virulence led to a long delay in
diagnosis and treatment. Any monoarthritis must continue to raise concern about
infection.
PMID- 17039148
TI - Renal microtophi in a patient with lupus nephritis and tophaceous gout.
AB - This case describes a 58-year-old female with systemic lupus erythematosus (SLE)
and coexistent chronic tophaceous gout. A renal biopsy showed concurrent lupus
nephritis and renal medullary microtophi, confirmed by electron and polarizing
microscopy, respectively. Whereas clinical SLE and gout have already been shown
to be rarely associated, this case further illustrates the presentation of these
two diseases in a single renal specimen. In this patient the gout began shortly
after menopause without known risk factors and before any overt renal disease or
signs of SLE. The tophaceous gout antedating the SLE, as well as the apparently
benign course of illness, suggest that the pathologic effects of SLE and gout on
the kidneys are based on independent mechanisms and may not necessarily aggravate
each other. Treatment of the gout with allopurinol may have contributed to
improved renal function.
PMID- 17039149
TI - A report from the Mexican Congress of Rheumatology.
PMID- 17039150
TI - Practice tip: improving zipper use with a key ring.
PMID- 17039152
TI - Can parvovirus B19 infection trigger adult Still's disease? Report of a case
controlled with infliximab.
PMID- 17039153
TI - Inclusion body myositis unresponsive to etanercept.
PMID- 17039154
TI - Should we be using more arthroscopy for septic arthritis?
PMID- 17039155
TI - Treatment for JRA in the New Millennium.
PMID- 17039156
TI - The Ehlers-Danlos syndromes: instructive for all cases of joint hypermobility?
PMID- 17039157
TI - Failure to recognize CPPD disease as a cause of fever/mental status change: why
does this happen?
PMID- 17039158
TI - Intravenous immunoglobulin in pregnancies complicated by the antiphospholipid
syndrome: what is its role?
PMID- 17039159
TI - Current medication choices in juvenile rheumatoid arthritis II--update of a
survey performed in 1993.
AB - The documentation of treatments used for Juvenile Rheumatoid Arthritis (JRA) is
important to allow for the evaluation of practice patterns for future outcome
studies. A survey of nine pediatric rheumatologists was performed between
September 1999 and February 2000. Each of the physicians prospectively recorded
demographic and treatment information on consecutively sampled JRA patients
(n=395). Pauciarticular onset JRA was present in 46%, polyarticular onset JRA in
35%, and systemic onset JRA in 19% of the children. Naproxen was the most
frequently prescribed medication (55% of the patients), followed by methotrexate
(MTX), which was used in 39% of the patients. Folic acid supplementation (1
mg/day) was provided to 69% of the patients treated with MTX. Etanercept was used
in 11% of the children. Eleven percent of the patients received corticosteroids,
and 13% of children on corticosteroids took calcium supplements. Uveitis was
present in 8% and had a chronic course in 79% of those cases. Although systemic
medications were used in 50% of the children with uveitis to control eye
inflammation, severe damage to the eyes developed in 30% of them. Fourteen
percent of the patients required gastroprotective medications. Compared with
findings of a similar survey performed in 1993, there was no significant change
in the frequency of use of naproxen, but nabumetone is now more often prescribed,
and COX-2 inhibitors have been introduced in the therapy of JRA. Changes among
second-line agents used for JRA have also occurred, although there was no change
in the frequency of use of MTX or corticosteroids. JRA continues to be a
treatment challenge for the practicing pediatric rheumatologist. Patients often
show incomplete response to the currently available medications. Therefore, new
therapeutic agents need to be evaluated for their use in JRA, and the treatment
of JRA associated uveitis especially needs to be improved.
PMID- 17039160
TI - Adult onset Still's disease: clinical features and outcome in 16 Thai patients.
AB - The clinical features of adult onset Still's disease (AOSD) have rarely been
described in Thai patients. We report the clinical manifestations, laboratory
findings, and outcome of 16 Thai patients with AOSD, and compare these findings
with those of the western and other oriental series. Fourteen patients (87.5%)
had the onset of their disease between 16-35 years of age. The most common
features presented were fever (100%), arthralgia and myalgia (100%), significant
weight loss (84.6%), arthritis (81.3%), skin rashes (68.8%), sore throat (62.5%),
elevated erythrocyte sedimentation rate (100%), leukocytosis (93.8%), and liver
dysfunction (75%). Pleuro-pericarditis and abdominal pain were uncommon. All but
2 patients required corticosteroids to control their systemic disease activity.
The clinical course of 13 patients, who were followed for more than 12 months,
was monocyclic systemic disease in four cases, polycyclic systemic disease in
five, chronic articular monocyclic systemic in one, and chronic articular
polycyclic systemic in three. When compared with western and other oriental
series, the AOSD in Thai patients shared similar clinical features and laboratory
findings, suggesting that mechanisms of pathogenesis may be similar in patients
from widely different genetic backgrounds and geographic locations.
Corticosteroids were frequently required and dramatically effective.
PMID- 17039161
TI - Symptoms and functional health status of individuals with Ehlers-Danlos syndrome
(EDS).
AB - Ehlers-Danlos syndrome (EDS) is an inherited connective tissue disorder that can
have a substantial impact on daily life. The aims of this study were to describe
the symptoms reported in a group of individuals with EDS and to investigate the
impact on functional health status by means of the Sickness Impact Profile (SIP).
Seventy-seven individuals, members of the Swedish EDS Association, completed 2
mailed questionnaires. The most frequent symptoms were related to activity, e.g.,
joint problems (75%), to pain (71%), and to skin/tissue (52%). Pain was reported
by 37 individuals (48%) as their most severe symptom. The SIP results showed an
overall mean score of 13.0 (females 13.9, males 5.6), compared with a Swedish
reference group with a SIP score 1.3. Women with EDS reported a better functional
health status than females with rheumatoid arthritis (overall SIP score 13.9
versus 21.4). In comparison with women with fibromyalgia, the EDS females rated
their functional health status as worse on the physical dimension (p <0.05) and
the subscale home management (p <0.05), and as better on the subscale work (p
<0.05). Impact of EDS on the individual's daily life needs to be acknowledged,
assessed, and evaluated in healthcare.
PMID- 17039162
TI - Bone mineral density and bone turnover markers in a group of male ankylosing
spondylitis patients: relationship to disease activity.
AB - Conflicting data have been published about osteoporosis and bone turnover markers
in patients with ankylosing spondylitis (AS). The aim of this study was to
determine bone mineral density (BMD) of the lateral lumbar spine in a group of
male patients with AS and to investigate the relationship between clinical
parameters and markers of bone turnover. Thirty-two consecutive AS patients with
a mean disease duration of 14.8 years and 32 control subjects were included.
Demographic and clinical characteristics were recorded. The Bath Ankylosing
Spondylitis Disease Activity Index (BASDAI) was used to determine the activity of
disease. BMD was determined for the lateral lumbar spine in both patients and
control groups. Serum osteocalcin and urinary N-telopeptide were measured as bone
turnover markers in patient and control groups. Although the mean values of
lumbar BMD in AS patients tended to be lower than in the control group, the
difference was not statistically significant. Osteoporosis was observed in 11
(34.3%) of AS patients and in 2 (6.2%) of the control group. Osteocalcin levels
were significantly higher in AS patients in comparison with control subjects (p <
0.05). In the subgroup analysis according to the activity of the disease,
erythrocyte sedimentation rate and N-telopeptide levels were significantly higher
in the severely active group when compared with that in mild or moderate disease
groups. Active AS patients compared with the control group had significantly
lower BMD and significantly higher N-Telopeptide levels (p < 0.05). The levels of
BASDAI scores and N-telopeptide values correlated significantly with each other.
The incidence of osteoporosis is high in AS patients, and patients with active
disease are especially at risk for developing osteoporosis. The monitoring of
bone turnover markers and disease activity indices may help to predict patients
at risk. Prophylactic and therapeutic strategies are needed to struggle against
bone loss in patients with this disabling condition.
PMID- 17039163
TI - Fever with acute arthritis in calcium pyrophosphate dihydrate deposition disease:
a missed explanation for altered mental status in elderly patients?
AB - Calcium pyrophosphate dihydrate (CPPD) deposition disease is a relatively common
condition primarily affecting the elderly. Various clinical presentations ranging
from an acute arthritis resembling gout (pseudogout) to fever of unknown origin
have been reported. We describe four elderly patients with fever and altered
mental status. Each patient underwent an extensive unrevealing work-up. An acute
arthritis missed by the health-care team in their initial evaluation was later
identified, leading to rheumatologic consultation and subsequent diagnosis of
CPPD disease after joint aspiration and synovial fluid analysis. Defervescence
and resolution of mental status changes occurred after improvement of the
arthritis. Awareness that CPPD disease may present with systemic symptoms,
including fever and altered mental status, may assure careful examination of
joints and can prevent unnecessary testing and diagnostic delay.
PMID- 17039164
TI - Acute motor-sensory axonal neuropathy associated with active systemic lupus
erythematosus and anticardiolipin antibodies.
AB - Acute motor-sensory axonal neuropathy (AMSAN) is an axonal variant of Guillian
Barre syndrome (GBS) that presents with acute ascending quadriparesis. This has
generally been described in association with Campylobacter jejuni infections or
with anti-ganglioside antibodies. Known cases have shown a slow recovery and a
poor prognosis. We report a case with clinical and electrophysiological evidence
of AMSAN in association with active systemic lupus erythematosus (SLE) and
anticardiolipin antibodies but not the other associations, with a rapid response
to combination immunosuppressant and intravenous immunoglobulin (IVIg) therapy.
The association between AMSAN and SLE has not been previously described. This
case illustrates that early recognition and the utilization of electrophysiologic
techniques may be beneficial in the diagnosis and management of GBS associated
with SLE. Fulminant or rapidly progressive cases should be managed in specialized
intensive care units. Combination therapy of immunosuppressants and IVIg may be
beneficial in non-vasculitic axonal radiculo-neuropathies associated with SLE,
resulting in good outcomes.
PMID- 17039165
TI - Polymyositis evolving after rhabdomyolysis associated with HMG-CoA reductase
inhibitors: a report of two cases.
AB - 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are commonly
used for treatment of hyperlipidemia and its deleterious effects. Myotoxicity has
been associated with use of these agents. We report two cases of inflammatory
myopathy in patients receiving these agents that did not respond to drug
withdrawal and required immunosuppressive treatment. One of these patients
developed an antibody to histidyl tRNA synthetase or Jo-1, an autoantibody
associated with idiopathic inflammatory myopathies. We suggest that HMG-CoA
reductase inhibitor-associated myotoxicity may trigger an immune-mediated
inflammatory myopathy. Patients whose muscle abnormalities do not resolve with
drug withdrawal should be considered for muscle biopsy.
PMID- 17039166
TI - Intravenous immunoglobulin to prevent recurrent thrombosis in the
antiphospholipid syndrome.
AB - The antiphospholipid syndrome (APS) occurs as a primary entity or in association
with autoimmune diseases, malignancies, or medications. Conventional treatment
for APS-associated thrombosis involves the use of anticoagulants such as aspirin,
heparin, and warfarin. Alternative treatment options are limited. We report on a
patient with APS who failed conventional therapy but had clinical improvement and
a decline in anticardiolipin (aCL) antibody titers during treatment with monthly
intravenous immunoglobulin (IVIg). Anticardiolipin antibodies IgG, IgA, and IgM
were measured before initiating IVIg and before each subsequent infusion of IVIg.
The patient was also evaluated for the presence of thromboses during the
treatment period. IgG and IgA aCL levels were elevated initially, and there was a
significant decrease in anticardiolipin IgG and IgA levels during treatment
without further episodes of thrombosis. IVIg may be an alternative therapy for
recurrent thrombosis in the antiphospholipid antibody syndrome.
PMID- 17039167
TI - A case of atorvastatin combined toxic myopathy and inflammatory myositis.
AB - Muscle toxicity is one adverse reaction reported with the use of 3-hydroxy-3
methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). This toxicity
may include asymptomatic elevations of muscle enzymes, weakness, myalgia, and
myositis. High doses of statins, or the combination of statins with other anti
cholesterol medications, increase the risk of toxicity. In addition, case reports
of systemic and autoimmune reactions such as lupus, nephritis, vasculitis, and
myositis, suspected to be associated with statins, have been reported. Our 76
year-old patient demonstrates a case of serologically and biopsy-proven
inflammatory polymyositis, combined with a statin toxic myopathy. His symptoms
and enzyme abnormalities resolved with both the removal of the statin medication
and the institution of immunosuppressive therapy. Investigation of muscle enzyme
elevation and weakness that do not resolve with statin removal is warranted.
Certain muscle biopsy findings, including mononuclear cell infiltrate,
distinguish the etiology as inflammatory/possibly autoimmune and do not suggest
statin myopathy.
PMID- 17039168
TI - Pericardial effusion and cardiomyopathy following arthritis with parvovirus B19
infection: response to intravenous immunoglobulin.
AB - We describe a 65-year-old female who presented with arthritis involving the small
joints of her hand, wrists, and knee, fever, rash, and leukocytosis. During the
course of her illness, she developed elevated transaminases, myositis, bilateral
pleural effusions, a large pericardial effusion compressing the right atrium, and
cardiomyopathy with impaired left ventricular function. The patient had evidence
of acute parvovirus B19 infection by serology, although parvovirus specific DNA
sequences from peripheral white blood cells were negative by polymerase chain
reaction. This illness raised concern about possible collagen vascular disease.
Low titers of antinuclear antibodies were present transiently, and other
autoantibodies were undetected. Treatment with intravenous immunoglobulin
resulted in dramatic resolution of her disease manifestations. Pericardial
effusion and cardiomyopathy may be rare sequelae of parvovirus B19 infection. The
apparent improvement with intravenous immunoglobulin could have been related to
clearance of infection or down regulation of host immune response.
PMID- 17039169
TI - Coexistent lyme disease and parvovirus infection in a child.
AB - Infectious diseases commonly cause illnesses that mimic rheumatic diseases. Both
Lyme disease and Parvovirus B19 infections produce arthritis, rashes, and a
systemic illness that may be thought to represent a chronic rheumatic disease. In
the case presented, a child with both infections simultaneously exhibited
arthralgias, aseptic meningitis, and a facial rash. The features of Lyme disease
and Parvovirus B19 infection that may mimic systemic lupus erythematosus include
a facial rash, often in a malar distribution, hematologic abnormalities,
arthritis, neurologic disorders, and autoantibody positivity. Given the proper
season and geographical location, one must consider the possibility of co
infection with these two organisms, especially in those with atypical rheumatic
complaints.
PMID- 17039171
TI - Molecular biology and immunology for clinicians, 14: Antigen presenting cells-
Class II.
AB - Pivotal to immunity and auto-immunity is the ability of the human immune response
to make antigen-specific responses, both cellular and humoral. T- and B-cells
contain within themselves the ability to recognize and react to specific
antigens, but they must be made aware of the presence of their target in the
surrounding environment to respond. Turns out this part of the education of T
cells (not B-cells, which are activated by specific antigens in a different
manner) is provided by a large number of cells, all coming under the umbrella
term: antigen-presenting cells. Understanding how these cells take up molecules
from the environment or acquire protein molecules from the intracellular milieu,
manipulate them, and then offer the modified material to engage potentially
responding cells in an immunological educational conversation is crucial to
understanding normal immune function and, of course, auto-immunity and other
forms of immune dysregulation. In the broadest of terms, there are two sources of
proteins: endogenous (produced within the cell) and exogenous (produced outside
of the cell), and there are two not entirely mutually exclusive pathways involved
in antigen processing and presentation. To decrease confusion between these two
separate pathways antigens, I will proceed with a description of the latter in
this paper and cover the former in the next paper in this series. So, now on to
antigen processing and presentation of proteins.
PMID- 17039172
TI - Practice tips: making a chair seat higher.
PMID- 17039174
TI - The clinical spectrum of anti-insulin receptor antibodies and autoimmune disease.
PMID- 17039175
TI - Psoriatic arthritis: genetics, immunology, and therapies.
PMID- 17039176
TI - Open trial of leflunomide for refractory psoriasis and psoriatic arthritis.
AB - Leflunomide was recently approved for the treatment of rheumatoid arthritis. Its
role in the treatment of psoriasis and psoriatic arthritis is unclear. Twelve
consecutive psoriatic arthritis patients who had not responded to at least one
disease modifying anti-rheumatic drug (DMARD) were started on leflunomide alone
or in addition to another DMARD. Global assessment of improvement in psoriasis
and psoriatic arthritis by the treating rheumatologist was scored on a 0-3 scale.
After 2-3 months of treatment, 8 patients had moderate to marked improvement in
both psoriasis and psoriatic arthritis. The improvement in modified tender joint
counts, patient's global assessments, and grip strengths was statistically
significant. However, physicians' global assessments and the modified swollen
joint counts did not reach a significant difference. Three patients whose
toxicity necessitated the temporary discontinuation of the drug were able to
resume the drug at lower dosage with clinical benefit. Leflunomide may prove to
be a useful agent for the treatment of recalcitrant cases of psoriasis and
psoriatic arthritis.
PMID- 17039177
TI - The prevalence of insulin receptor antibodies in patients with systemic lupus
erythematosus and related conditions.
AB - Autoantibodies to the insulin receptor have been demonstrated to antagonize the
physiologic actions of insulin, most often resulting in hyperglycemia
unresponsive to massive doses of insulin (type B insulin resistance). Patients
with these anti-insulin receptor antibodies typically have a coexistent
autoimmune disorder, most commonly systemic lupus erythematosus (SLE) or
undifferentiated autoimmune syndromes. Attempting to determine the prevalence and
significance of anti-insulin receptor antibodies, sera from consecutive patients
with SLE and early undifferentiated connective tissue disease (UCTD) were tested
for the presence of anti-insulin receptor antibodies by radio-immuno assay.
Thirty-eight patients participated in the study. Twenty-six had SLE and 12 had
UCTD. One patient with SLE (2.6%) was positive for anti-insulin receptor
antibodies. None of the patients demonstrated evidence of insulin resistance,
hypoglycemia, ovarian hyperandrogenism, or acanthosis nigricans, findings
commonly linked with the presence of anti-insulin receptor antibodies. The
results presented here indicate that the incidence of anti-insulin receptor
antibodies in patients with SLE or UCTD, without associated history of altered
glucose metabolism, is quite low. Because in most cases the disturbance of
glucose metabolism dominates the clinical picture at presentation and the
associated systemic autoimmune syndrome presents either simultaneously with or
subsequent to the diagnosis of diabetes, the measurement of anti-insulin receptor
antibodies should be reserved for patients with indications of disordered glucose
homeostasis.
PMID- 17039178
TI - Colchicine induced neuromyopathy in a patient with normal renal function.
AB - A 69-year-old male on colchicine 0.6 mg twice a day for more than a year
developed subacute onset of painless proximal muscle weakness with significant
elevation of creatine phosphokinase (CPK) levels. He also experienced numbness
and tingling in the extremities. Nerve conduction studies revealed a mild axonal
neuropathy affecting the arms and legs while needle electromyography was
unremarkable. He refused a muscle biopsy. After withdrawal of colchicine, muscle
strength and serum CPK levels returned to normal over a period of 4 months.
Neuromyopathy is a well documented side effect of colchicine, and impaired renal
function has been the major risk factor in previously reported cases. In our
patient, neurological toxicity occurred in the presence of normal renal function.
The neuromyopathy is generally reversible on withdrawal of the drug. Colchicine
is to be used with caution in patients with impaired renal function, and even if
kidney function is normal, muscle strength must be monitored and serum CPK levels
checked if myopathy is suspected.
PMID- 17039179
TI - Aplastic anemia in systemic lupus erythematosus: a distinct presentation of
acquired aplastic anemia?
AB - Aplastic anemia is a rare but serious complication of systemic lupus
erythematosus (SLE) with an often dramatic and unanticipated onset. The
peripheral destruction of formed blood elements, which frequently accompanies the
syndrome, may obscure or delay the diagnosis of bone marrow suppression, and the
number of published cases may be an underestimate of the actual incidence of the
disease. Furthermore, the disease course may differ significantly from other
forms of acquired aplastic anemia and seems to carry a more favorable prognosis
once effectively diagnosed and treated. In addition, aplastic anemia may precede
other manifestations of SLE. Therefore, the possibility of bone marrow aplasia
should be excluded in all SLE patients with severe pancytopenia, and conversely,
the diagnosis of SLE should be explored in cases of aplastic anemia. Two patients
with aplastic anemia in SLE, one with aplastic anemia preceding the onset of SLE,
are described along with 15 cases reviewed from the English language literature.
The presentation, prognosis, treatment, and pathogenesis of aplastic anemia
complicating SLE are discussed. Recognition that cytopenias, especially
pancytopenia, may occur on the basis of inhibited myelopoesis rather than
peripheral destruction as either a harbinger of SLE or as a manifestation of
disease flare is important. This knowledge will prompt the astute clinician to
obtain screening antinuclear antibodies in the setting of otherwise unexplained
bone marrow acellularity or, given the prognosis of SLE associated aplastic
anemia, give early consideration to more aggressive immunosuppression.
PMID- 17039180
TI - Cytomegalovirus esophagitis as a treatable complication of systemic sclerosis.
AB - We report the case of a 51-year-old woman with a connective tissue disease of 8
years duration. She had been taking corticosteroids at a dose of 1 mg/kg/day and
azathioprine at a dose of 3 mg/kg/day for 1 month. Given the clinical suspicion
of systemic sclerosis (limited form of scleroderma), she was studied according to
a protocol including endoscopy to assess the degree to which the underlying
disease had affected the gastrointestinal tract. Endoscopy revealed a
asymptomatic severe esophagitis and a subsequent biopsy disclosed the presence of
cytomegalovirus. Cytomegalovirus pneumonia was also detected. Both processes were
successfully managed with intravenous ganciclovir (5 mg/kg/12 hr) for 21 days.
This report is a case of cytomegalovirus involving the esophagus in association
with systemic sclerosis in a patient immunosuppressed because of drugs that she
had been taking. This complication can be asymptomatic and is amenable to
treatment.
PMID- 17039181
TI - Pulmonary Takayasu's arteritis masquerading as acute pulmonary embolism.
AB - Pulmonary involvement may sometimes be the initial presentation of Takayasu's
arteritis (TA). Since the signs and symptoms of pulmonary TA may be subtle and
may not be easily distinguishable from other pulmonary diseases, one has to
maintain a high index of suspicion. Cases of pulmonary TA mimicking chronic
thromboembolism have been reported. We describe a patient with TA whose initial
presentation mimicked acute pulmonary embolism. The patient presented with a 3
day history of cough and shortness of breath and had multiple bilateral perfusion
defects on ventilation-perfusion scan, typical of acute pulmonary embolism.
However, the constellation of clinical features, elevated erythrocyte
sedimentation rate and the angiographic appearance helped us establish the
correct diagnosis of pulmonary Takayasu's arteritis. At a 6-year follow-up, the
patient had no worsening of pulmonary symptoms but presented with postural
dizziness with angiographic evidence of carotid and innominate artery stenosis;
she underwent arterial bypass grafting. In young women presenting with a clinical
picture of acute pulmonary embolism without the previous history (or risk
factors) of thromboembolism, pulmonary TA must be considered in the differential
diagnosis.
PMID- 17039182
TI - A muscle mass in a patient with polymyalgia rheumatica.
AB - We report the extremely uncommon case of a 77-year-old woman in whom a tumor
found to be a melanotic schwannoma, arising from the right rectus abdominis
muscle, was detected during investigation for a rheumatic disorder, finally
identified as polymyalgia rheumatica (PMR). Tumors of this type most commonly
occur in spinal nerve roots, and their clinical behavior is very difficult to
predict. As far as we are aware, this is the first reported case affecting the
aforementioned site. The challenging issue in this case concerns the possible
link between the 2 clinical conditions, in particular the development of PMR as a
paraneoplastic syndrome. Although such an association has not been reported, PMR
is included among the rheumatic disorders reported to be associated with
malignancies and occasionally with benign tumors. However, given that tumor
resection did not result in remission of PMR and symptoms improved rapidly with
prednisone, it seems likely that the above disorders might simply coexist.
PMID- 17039183
TI - Minor salivary gland punch biopsy for evaluation of Sjogren's syndrome.
AB - Incisional biopsy of labial salivary glands has been a valuable technique for
diagnosis of Sjogren's syndrome. This report describes a new technique using
punch biopsies that requires fewer resources and appears to be equally effective.
Fifty patients evaluated by punch biopsy all yielded adequate pieces averaging 6
glands per specimen. Two patients had transient numbness of the lip. There were
no other complications. Classical findings of Sjogren's histopathology were
demonstrable with these specimens. This technique is safe, less expensive, and is
proposed as a reliable alternative to incisional biopsy.
PMID- 17039184
TI - Periostitis in a patient with ulcerative colitis.
PMID- 17039185
TI - Molecular biology and immunology for clinicians 15: Antigen presenting cells-
class I.
AB - Class I-bearing antigen presenting cells (APCs) monitor intracellular proteins
which are cellular proteins made on a routine basis, endogenous proteins made by
stressed cells, proteins made by infected or transformed cells, or proteins made
by intracellular pathogens, e.g., viruses, chlamydiae, mycoplasma, Listeria, and
some Enterobacteriaceae. The mechanisms by which peptides interact with and are
expressed by class I complexes on the surface of APCs is described and contrasted
with the circumstances of class II antigen presentation.
PMID- 17039186
TI - Practice tips: teaching aid for bursitis.
PMID- 17039188
TI - Life-threatening hypokalemic paralysis and hypophosphatemic myopathy as initial
presentations of primary Sjogren's syndrome.
PMID- 17039189
TI - What really is Poncet's disease? Report of a case mimicking sarcoidosis.
PMID- 17039190
TI - Acute renal failure can occur with inappropriate use of a coxib.
PMID- 17039191
TI - The ever-expanding clinical spectrum of tuberculosis.
PMID- 17039192
TI - SAPHO: disease, syndrome, or category?
PMID- 17039193
TI - Should rheumatologists be evaluating acupuncture?
PMID- 17039194
TI - Acupuncture improves peripheral perfusion in patients with reflex sympathetic
dystrophy.
AB - Patients with stage II reflex sympathetic dystrophy syndrome (algodystrophy)
often describe a sensation of beneficial warmth in the affected limb when
receiving acupuncture treatment. In a case control study of 10 patients with
unilateral algodystrophy stage II, and 10 healthy sex and age-matched controls,
we investigated whether acupuncture has an effect in blood volume flow and
correlated this with a clinical assessment. Blood volume flow was measured by
duplex sonography before, during, and after acupuncture. During acupuncture,
blood volume flow increased significantly (+31.1%, p (one-tailed) = 0.024) in the
patients' effected limbs (by algodystrophy) compared with the patients' untreated
limbs (contralateral). It was also elevated compared with the controls' treated
limbs (+23.9%, p = 0.046). The corresponding data after acupuncture were +29.5%,
p = 0.057 and +38.3%p = 0.014. All but one patient reported improved symptoms.
However, only subjective improvement in function, not pain, was positively
correlated to the increase in blood volume flow. In patients with algodystrophy
stage II, a significant increase of blood volume flow was attributed to
acupuncture and was correlated to functional improvement.
PMID- 17039195
TI - A study of musculoskeletal manifestations in 12 patients with SAPHO syndrome.
AB - Synovium and synovial fluid findings in SAPHO (synovitis, acne, pustulosis,
hyperostosis, and osteitis) syndrome have not been well characterized, and only a
few patients have been described in the Americas. We describe clinical,
pathologic, and synovial fluid findings in 12 patients with the SAPHO syndrome:
hidradenitis suppurativa (7), acne fulminans or conglobata (3), acneiform
folliculitis (1) and palmoplantar pustulosis (1). Routine synovial fluid studies
were performed in 6 patients, and light and transmission electron microscopic
studies were performed in synovium in 2 patients and in bone in 1. The most
common musculoskeletal manifestations included erosive or non-erosive
oligoarthritis involving metacarpal phalangeal (MCP) and metatarsal phalangeal
(MTP) joints as seen in 9 patients, sclerosis of the sacroiliac joints as seen in
5 patients, and osteitis pubis as seen in 1. Three patients had signs of skeletal
hyperostosis. The patients with acne fulminans and acneiform folliculitis had
chronic aseptic multifocal osteomyelitis. Synovial fluid was sterile in 7, mildly
inflammatory in 5, and highly inflammatory in 2. Electron microscopic studies of
synovium in 2 patients and of bone in 1 were not useful to detect microorganisms.
Three African-American patients with hidradenitis suppurativa presented with
pyoderma gangrenosum, and 2 of them had leukocytoclastic vasculitis, and a life
threatening course unresponsive to antibiotics, corticosteroids and
immunosuppressive therapy. SAPHO in the Americas is most severe in African
Americans with hidradenitis suppurativa, and it presents with heterogeneous
musculoskeletal and cutaneous manifestations including erosive polyarthritis or
oligoarthritis with nonspecific mild inflammatory fluid. Leukocytoclastic
vasculitis and recalcitrant pyoderma gangrenosum were seen in 2 of our patients
with the most severe hidradenitis suppurativa. SAPHO syndrome may present with
clinical manifestations similar to those seen with seronegative
spondyloarthropathies, but it has distinctive cutaneous, radiographic articular,
and bone manifestations. Sites of chronic infection need aggressive antibiotic
therapy and may need surgical resection.
PMID- 17039196
TI - Prevalence and predictors of cervical involvement in psoriatic
spondyloarthropathy.
AB - Cervical spondylitis has been reported in 35%-75% of patients with psoriatic
arthritis (PsA), and this likely represents the highest frequency of cervical
involvement among the spondyloarthropathies. Although 2 patterns of cervical
spondylitis have been recognized in PsA, this may reflect a lack of a
satisfactory definition of cervical spondylitis in PsA. In a retrospective cross
sectional study, we analyzed the clinical records of 100 consecutive patients
recruited at a single university hospital who were diagnosed as having psoriatic
spondyloarthropathy on the basis of radiographic sacroiliitis. All patients were
involved in a clinicoradiologic study of the cervical column to evaluate the
frequency and the predictors of this involvement. Forty-one patients showed
radiographic signs of cervical involvement and 24 of them (58.5%) complained of
cervical pain and stiffness, whereas 17 (41.5%) had radiologic disease with no
symptoms. Arthritis duration (odds ratio, 1.08; 95% confidence interval, 0.99
1.19; p < 0.05) and peripheral erosive disease (odds ratio, 2.5; 95% confidence
interval, 1.91-6.92; p < 0.05) were found to be associated with cervical
spondylitis development. This study showed a high frequency of cervical
spondylitis among patients with psoriatic spondyloarthropathy, confirming
previous reports. Although none of our patients developed neurologic sequelae,
this report also showed that clinical symptoms of cervical pain and stiffness are
not a universal predictor of involvement of the cervical spine, and therefore,
patients with PsA with longer disease duration and erosive disease should be
screened radiologically to detect those cervical lesions (i.e., atlantoaxial
subluxation) with potential catastrophic complications.
PMID- 17039197
TI - Pathologic fracture of the femoral neck in a female soccer player.
AB - We report a case of a healthy, young, female soccer player who developed
progressive pain in her right hip. A bone cystic lesion was found in the right
femoral neck and proximal femur. The lesion was considered a benign bone cyst and
the patient was treated with injections of autologous bone marrow and grafting
into the femoral neck. However, the cystic lesion did not heal. Subsequently, the
patient fell and developed a fracture of the femoral neck that required internal
fixation. The bone biopsy showed characteristic histologic features of fibrous
dysplasia. A bone scan showed other areas of suspected dysplasia. Pamidronate
therapy was given, and a reduction of the increased uptake was seen on bone
scans. Fibrous dysplasia must be considered in the differential diagnosis of any
cystic bone lesion.
PMID- 17039198
TI - Multifocal tubercular dactylitis in an adult.
AB - Musculoskeletal tuberculosis (TB) is a rare manifestation of TB comprising 1%-3%
of all cases. We describe a patient who had multiple manifestations of skeletal
TB, including spondylitis, dactylitis, and Poncet's disease. The unusual features
include multifocal dactylitis, widespread disease in the absence of any risk
factor like HIV infection or immunosuppressive treatment, and absence of
pulmonary lesion. Treatment with appropriate drugs, using 4 agents for the first
2 months, led to complete recovery. TB can rarely present in an unusual way but
is very important to recognize, as with treatment it still carries a good
prognosis.
PMID- 17039199
TI - Disseminated Histoplasmosis Mimicking Felty's Syndrome.
AB - The successful treatment of rheumatoid arthritis often requires the use of
immunosuppressive medications. Although these agents have different potential
toxicities, they share in common the potential for permitting the development of
opportunistic infections. We describe 2 patients with chronic rheumatoid
arthritis treated with immunosuppressive agents who developed progressive
neutropenia with documented splenomegaly. The differential diagnosis included
Felty's syndrome versus bone marrow suppression from their immunosuppressive
medication. Although both patients had the triad of Felty's syndrome, high titer
seropositive rheumatoid arthritis with splenomegaly and neutropenia, the
diagnosis of this syndrome relies on excluding other potential causative factors.
Further investigation revealed that both patients had disseminated histoplasmosis
with bone marrow involvement, which most likely represented reactivation from
prior exposure to Histoplasma capsulatum. Opportunistic infections such as
disseminated histoplasmosis can mimic other disease processes, including Felty's
syndrome, and are important to consider when there is a change in the clinical
status of patients with rheumatic disease who are immunocompromised.
PMID- 17039200
TI - Hepatitis C virus infection, inflammatory myopathy, and pulmonary fibrosis: are
they related?
AB - We describe the clinical findings, laboratory and ancillary studies, and
histopathologic findings of 2 patients with hepatitis C virus infection who
developed inflammatory myopathy and interstitial lung disease. A review of
pertinent literature revealed several other patients with a similar cluster of
clinical manifestations. The inflammatory myopathy in the cases reported here was
atypical and distinct from that found in the anti-synthetase syndrome because it
was characterized by mild or intermittent elevation of creatine phosphokinase,
absence of anti-JO1 antibodies, and excellent response to oral corticosteroids.
Thus, this report supports the hypothesis that hepatitis C virus infection may
cause both inflammatory myopathy and pulmonary fibrosis. We suggest that
evaluation for hepatitis C virus infection should be pursued in all patients with
inflammatory myopathy and pulmonary fibrosis irrespective of anti-JO1 status. We
further suggest that hepatitis C should be considered as another cause of
myositis and interstitial lung disease in addition to the anti-synthetase
syndrome.
PMID- 17039201
TI - Drug-induced amyopathic dermatomyositis.
AB - Amyopathic dermatomyositis is a rare condition. We describe the clinical and
histopathologic findings of a 53-year-old woman who developed cutaneous lesions
similar to those described in dermatomyositis after fibrate therapy for
hypertriglyceridemia. Our patient fits the proposed criteria for amyopathic
dermatomyositis, and after 8.5 years, muscular involvement has not been detected,
although the dermatologic lesions are still present despite different treatments
reported to treat this condition (steroids, antimalarials, methotrexate,
dapsone). However, an initial good response has been observed with thalidomide, a
drug used increasingly in the dermatologic field. As far as we know, this case is
the first of drug-induced amyopathic dermatomyositis.
PMID- 17039202
TI - Persistent back pain after a fall.
PMID- 17039205
TI - Fever and knee effusions.
PMID- 17039203
TI - Molecular biology and immunology for clinicians 16: Dendritic cells and their
role in immunology.
AB - As is so often the case in immunology, with the passage of time and further
research, cells of obscure lineage and function become the darlings of the field.
Such is the case with dendritic cells. Probably the most potent antigen
presenting cells of all, dendritic cells are pivotal in the education and
coaching of T-cells, B-cells, and natural killer cells, putting the dendritic
cell firmly in place to influence both innate and antigen-specific immune
reactivity. Thus, understanding dendritic cells' function and how they switch
morphologically and functionally during their maturation may be very important if
we are to manipulate dendritic cells to suppress or enhance immunologic function
in disease. There is sure to be more about dendritic cells in the oncology,
clinical immunology, and rheumatology literature over the coming years as we
learn to control dendritic cell function.
PMID- 17039206
TI - Practice tips: relief of sciatica with a foot rest.
PMID- 17039208
TI - Pneumocystis carinii pneumonia associated with leflunomide therapy for rheumatoid
arthritis.
PMID- 17039209
TI - The diagnosis of systemic lupus erythematosus.
PMID- 17039210
TI - Drugs for treatment of ADHD.
PMID- 17039211
TI - Usefulness of disability to sub-classify chronic low back pain and the crucial
role of rehabilitation.
PMID- 17039212
TI - General Medicine and Rehabilitation: bio-psycho-social answers to back pain in
its different stages.
PMID- 17039213
TI - Falls in a rehabilitation setting: functional independence and fall risk.
AB - AIM: With this study we wanted to determine the incidence, characteristics and
consequences of falls in our rehabilitation setting. METHODS: An observational
study was carried out in a rehabilitation setting for postacute orthopedic and
neurological inpatients. Three-hundred and twenty patients were enrolled. Falls
risk factors (Downton index [DI] and other known parameters), disability
(functional independence measure [FIM]) and balance (Berg balance scale [BBS])
were assessed at admission. Falls that occurred during the rehabilitation stay
were prospectively classified (St. Louis Older Adult Service and Information
System [OASIS] system) and analyzed. RESULTS: Forty patients experienced a fall
(12.5%). The faller group was characterized by a major clinical complexity; 70%
of fallers were neurological patients and 30% presented cognitive impairment
(mini mental state examination [MMSE] <24). They presented a statistically
significant worse score on FIM (motor and cognitive), BBS and DI at admission,
with 74% predictability of falls as measured by total FIM score and age. Falls
recorded with the OASIS classification showed a prevalence (52.5%) for not
bipedal (wheelchair transfer) and self-generated falls; 35% were intrinsic falls
(caused by subject-specific factors) and 12.5% extrinsic falls (caused by
environmental factors). Falls resulted in only minor clinical consequences,
except for one rib fracture, but led to a significant increase in length of stay.
CONCLUSIONS: In a rehabilitation centre, for good management of resources and
safe prescriptions of a patient's independence in activities of daily living,
fall risk is better evaluated with appropriate scales.
PMID- 17039214
TI - Biomechanics of lower limb raising from the supine position.
AB - AIM: This study analyses the kinematics of the lower limb raising movement from
the supine position and the electromyography activity of the muscles involved.
METHODS: Twenty healthy right hand subjects performed the right lower limb
raising from the supine position, starting from the clinical bed plane and up to
a 70 degrees inclination of the thigh over the horizontal plane, while the knee
was kept flexed at 120 degrees by a soft splint. The same exercise was executed
with no resistance and with 2 kg and 8 kg respectively applied to the ankle. The
kinematics was recorded utilising an optoelectronic system, whereas the
electromyography activity was recorded by a surface electromyography (EMG)
applied to the following muscles: right rectus femoris, left biceps femoris,
rectus abominalis from both sides and dorsal major from both sides. RESULTS: In
all the cases the pelvis performed a backwards rotation retroversion. The highest
increase of EMG activation was recorded on the right rectus femoris as well as on
the left biceps femoris; the increase was lower in the right rectus abdominis and
in the right dorsal major, whereas it was minimum in the left rectus abdominis
and in the left dorsal major. A great variability in the activation times was
reported in the various muscles of the different subjects, regardless of the
trials. The only muscle anticipating the right rectus femoris activation was the
left biceps femoris. CONCLUSIONS: The research has shown how the simple movement
under study is more complex than what is usually described by the text books,
both in regard to the kinematics and to muscles' actions. Even the individual
variability in utilising the agonist and stabilisation muscles can be of
relevance for a more rational utilisation of the physical exercise in motor re
education.
PMID- 17039215
TI - Pain relief in early rehabilitation of rotator cuff tendinitis: any role for
indirect suprascapular nerve block?
AB - AIM: The purpose of the trial was to evaluate the efficacy of suprascapular nerve
block (SSNB) to relieve the shoulder pain, ameliorate recovery after
physiotherapy and reduce disability due to a rotator cuff tendinitis (RCT). A
prospective, randomized, comparison cross over investigation was performed in the
setting of a large inpatient rehabilitation unit with more than 200 admissions
annually. METHODS: A total of 40 potential study subjects, who complained of
shoulder pain from a RCT, were enrolled and randomly assigned to standard
rehabilitation treatment plus SSNB (Group A) or to standard rehabilitation
treatment alone (Group B). The UCLA shoulder rating scale was used to assess the
shoulder mobility on admission and discharge, and to calculate the percentage of
potential improvement achieved during rehabilitation (effectiveness). A pain
visual analogic scale was used to serially assess pain. At the end of the trial,
a self-report questionnaire evaluated whether patients could sleep and achieve
activity of day life carry out everyday activities better than they could before
treatment. RESULTS: Forty patients suffering from RCT entered the study. Those
receiving nerve block from the beginning of the treatment in addition to standard
rehabilitation therapy reported significantly less pain during physiotherapy and
better final outcomes. During treatment with SSNBs, patients reported a more
significant reduction in the intensity of pain and a better reduction of pain
during sleep and rehabilitation exercises in comparison to with the standard
therapy alone. A statistically significant inverse correlation was found between
shoulder pain and mobility. CONCLUSIONS: The results indicate that combining
nerve block with standard rehabilitative therapy may improve the final outcome of
painful RCT. It decreased the severity and frequency of the perceived pain,
improved the compliance with physiotherapy, restored more normal sleep patterns,
and increased compliance with the rehabilitation program. This result proves to
be an effective, safe and inexpensive therapeutic option for patients suffering
from painful disabling shoulder tendinitis.
PMID- 17039216
TI - Two different techniques in the rehabilitation treatment of low back pain: a
randomized controlled trial.
AB - AIM: The Back School is a widely accepted and effective method for treating low
back pain, whereas no scientific evidence exists about the effects of the Pilates
CovaTech method. With this study we wanted to evaluate the efficacy of this new
method in patients with low back pain. METHODS: Fifty-three patients with at
least 3 months of nonspecific low back pain were entered into a Pilates therapy
or a Back School treatment group, 43 of which completed the study. Small exercise
groups of 7 patients each followed a daily kinesitherapy protocol for 10 days.
Evaluations were performed at the start of the study and then at 1, 3 and 6
months after the beginning of treatment. We used the Oswestry Low Back Pain
Disability Scale (OLBPDQ) to assess disability and the visual analog scale (VAS)
to evaluate pain. RESULTS: Demographic and baseline clinical characteristics were
similar for both groups. A significant reduction in pain intensity and disability
was observed across the entire sample. The Pilates method group showed better
compliance and subjective response to treatment. CONCLUSIONS: The results
obtained with the Pilates method were comparable to those achieved with the Back
School method, suggesting its use as an alternative approach to the treatment of
non specific low back pain.
PMID- 17039217
TI - Follow-up in persons with traumatic spinal cord injury: questionnaire
reliability.
AB - AIM. The aim of this study is to show the compliance and the test-retest
reliability of the questionnaire. METHODS: Construction of a structured
questionnaire to perform a phone follow-up in 511 persons with traumatic spinal
cord injury (SCI) 4 years after discharge from the first rehabilitative
hospitalization. The questionnaire is structured in 24 items, comprising
exclusion (closed questions) answers and 3 analogic scale answers, divided into 7
aspects: clinical conditions, sentimental relationships, quality of life,
autonomy, mobility, occupation, social reintegration. A pilot survey on 20
subjects with SCI, hospitalized in different periods in 2 rehabilitation centers,
was performed to check the questionnaire's feasibility and reproducibility. The
persons were interviewed twice by telephone, with an interval of about one month,
by a psychologist. The questionnaire was completed during one single phone
conversation. RESULTS: No missing answers were recorded. The test run for this
questionnaire showed high reproducibility based on the large numbers of questions
with 100% correspondence between the answers ''before'' and ''after''. For most
of the other questions this factor ranged between 80% and 99%, and for 2
questions on the analogic scale between 30% and 50%. CONCLUSIONS: The data
collected by this pilot survey show the reliability of this questionnaire for all
answers, save for the quantification of subjective variables.
PMID- 17039218
TI - Persistence of range of motion in dorsiflexion, when the triceps surae muscles
weaken, worsens stance and gait in Charcot-Marie-Tooth disease. A case report.
AB - Charcot-Marie-Tooth disease is a genetically heterogeneous disorder,
characterized by length dependent degeneration of motor and sensory nerve fibers.
The variability in clinical severity is typical, and is considered the result of
environmental factors interacting with the genotype. We report the case of 2
sisters who present the same muscle involvement, with complete atrophy below the
knees, but a very different degree of disability: the milder affected sister can
walk independently for 1 km, the more severe for 50 m only. The factor,
responsible for the different functional impairment, is the persistence of ankle
dorsiflexion. This is the result of prolonged stretching of the heel cords in the
more severely affected sister, which destabilizes stance and ambulation. On the
contrary, the milder affected sister presents a slight equinus deformity well
compensated by wearing shoes with a bit of heel. The presented cases and
biomechanics suggest that the persistence of range of motion in dorsiflexion,
when the triceps surae muscles weaken beyond a certain degree, represents an
important negative factor of clinical variability in Charcot-Marie-Tooth disease;
this can be averted by correct rehabilitation management.
PMID- 17039219
TI - The challenge of uncovering outcome in neurological rehabilitation.
PMID- 17039220
TI - Quality of life and aphasia. Multicentric standardization of a questionnaire.
AB - AIM: It is important to assess aphasics' quality of life in order to plan a
rehabilitation treatment. To date such a tool is still missing for Italian
patients. This paper reports normative data of the Italian version of SAQOL-39, a
British questionnaire aimed to assess aphasics' quality of life. It consists of
39 items, divided into 4 subdomains (Physical, Communication, Psychosocial and
Energy). METHODS: Forty-two patients coming from 3 different Speech Therapy
Services were enrolled. All patients completed speech therapy before examination.
They were submitted to the Italian SAQOL-39 and 2 screening tests for aphasia: 1)
Communication Assessment Scale according Goodglass and Kaplan; 2) Franchay
Aphasia Screening Test (FAST). A receptive FAST score of 7 out of 15 was used as
a cut-off score for SAQOL-39 administration. RESULTS: The Italian SAQOL-39 showed
good internal consistency (full scale Cronbach's alpha 0.939). Cronbach's alpha
for every subdomains ranged from 0.950 (Communication) to 0.720 (Energy). Fluent
aphasics gave significantly higher scores than nonfluent ones on full scale, and
all out of Energy subdomains. Furthermore gravity of aphasia correlated with both
full scale and Communication subdomain scores. CONCLUSIONS: In authors' opinion,
the Italian SAQOL-39 shares many psychometric features with the English one. This
questionnaire seems to be suitable for clinical practice.
PMID- 17039221
TI - A randomised controlled cross-over trial of aerobic training versus Qigong in
advanced Parkinson's disease.
AB - AIM: To investigate the effects of an aerobic training in subjects with
Parkinson's disease (PD) as compared to a medical Chinese exercise (Qigong).
METHODS: DESIGN: randomized controlled trial with a cross over design. SETTING:
PD out-patients referred to a Neurorehabilitation facility for the management of
motor disability. SUBJECTS: 26 PD patients in Hoehn and Yahr stage II to III
under stable medication were randomly allocated to either Group AT1+QG2
(receiving 20 aerobic training sessions followed by 20 ''Qigong'' group sessions
with 2 month interval between the interventions), or Group QG1+AT2 (performing
the same treatments with an inverted sequence). MAIN OUTCOME MEASURES: clinical
effects of treatment were sought through the Unified Parkinson's Disease Rating
Scale (UPDRS), Brown's Disability Scale (B'DS), six-Minute Walking Test (6MWT),
Borg scale for breathlessness, Beck Depression Inventory (BDI) and Parkinson's
Disease Questionnaire-39 items (PDQ-39). A spirometry test and maximum
cardiopulmonary exercise test (CPET) were also performed to determine the
pulmonary function, the metabolic and cardio-respiratory requests at rest and
under exercise. All measures were taken immediately before and at the completion
of each treatment phase. RESULTS: The statistical analysis focusing on the
evolution of motor disability and quality of life revealed a significant
interaction effect between group and time for the 6MWT (time x group effect: F:
5.4 P=0.002) and the Borg scale (time x group effect: F: 4.2 P=0.009). Post hoc
analysis showed a significant increase in 6MWT and a larger decrease in Borg
score after aerobic training within each subgroup, whereas no significant changes
were observed during Qigong. No significant changes over time were detected
through the analysis of UPDRS, B'DS, BDI and PDQ-39 scores. The analysis of
cardiorespiratory parameters showed significant interaction effects between group
and time for the Double Productpeak (time x group effect: F: 7.7 P=0.0003), the
VO(2peak) (time x group effect: F: 4.8 P=0.007), and the VO(2)/kg ratio (time x
group effect: F: 4.3 P=0.009), owing to their decrease after aerobic training to
an extent that was never observed after Qigong treatment. CONCLUSIONS: Aerobic
training exerts a significant impact on the ability of moderately disabled PD
patients to cope with exercise, although it does not improve their self
sufficiency and quality of life.
PMID- 17039222
TI - Constraint-induced movement therapy: an original concept in rehabilitation.
PMID- 17039223
TI - The learned nonuse phenomenon: implications for rehabilitation.
AB - Research on monkeys with a single forelimb from which sensation is surgically
abolished demonstrates that such animals do not use their deafferented limb even
though they possess sufficient motor innervation to do so, a phenomenon labeled
learned nonuse. This dissociation also occurs after neurological injury in
humans. Instruments that measure these two aspects of motor function are
discussed. The effects of a neurological injury may differ widely in regard to
motor ability assessed on a laboratory performance test in which movements are
requested and actual spontaneous use of an extremity in real-world settings,
indicating that these parameters need to be evaluated separately. The methods
used in Constraint-Induced Movement therapy (CI therapy) research to
independently assess these two domains are reliable and valid. We suggest that
these tests have applicability beyond studies involving CI therapy for stroke and
may be of value for determining motor status in other types of motor disorders
and with other types of treatment. The learned nonuse formulation also predicts
that a rehabilitation treatment may have differential effects on motor
performance made on request and actual spontaneous amount of use of a more
affected upper extremity in the life situation. CI therapy produces improvements
in the former, but focuses attention on the latter and, in fact, spontaneous use
of the limb is where this intervention has by far its greatest effect. The
evidence suggests that this result is driven by use of a ''transfer package'' of
techniques, which can be used with other therapies to increase the transfer of
improvements made in the clinic to the life situation. The use of CI therapy in
humans began with the upper extremity after stroke and was then extended for the
upper extremity to cerebral palsy in young children (8 months to 8 years old) and
traumatic brain injury. A form of CI therapy was developed for the lower
extremities and was used effectively after stroke, spinal cord injury, and
fractured hip. Adaptations of CI therapy have also been developed for aphasia (CI
aphasia therapy), focal hand dystonia in musicians and phantom limb pain. The
range of these applications suggests that CI therapy is not only a treatment for
stroke, for which it is most commonly used, but for learned nonuse in general,
which manifests as excess motor disability in a number of conditions which until
now have been refractory to treatment.
PMID- 17039224
TI - Constraint-induced movement therapy: characterizing the intervention protocol.
AB - Constraint-induced movement therapy (CI therapy) is a rehabilitation treatment
approach that improves more-affected extremity use following a stroke, especially
in the life situation. The originators of the approach describe CI therapy as
consisting of a family of therapies including a number of treatment components
and subcomponents. When thinking of CI therapy, rehabilitation researchers and
clinicians frequently cite a restraining mitt on the less affected arm as the
main active ingredient behind improvements in motor function. However,
substantial data suggest that restraint makes actually a relatively small
contribution to treatment outcome. This paper provides a detailed description of
the multiple treatment elements included in the CI therapy protocol as used in
our research laboratory. Our aim is to improve understanding of CI therapy and
the research supporting its use.
PMID- 17039225
TI - Neuroplasticity and constraint-induced movement therapy.
AB - Recent years have seen a proliferation of animal and human studies that have
associated significant changes in regional brain physiology with sustained
altered environmental or somatic stimuli. The behavioral consequences in such
instances can be adaptive or maladaptive. As would be expected, constraint
induced movement therapy (CI therapy), which has been found to be beneficial for
chronic stroke hemiparesis, has been repeatedly associated with significant
plastic brain changes in a variety of studies that have included transcranial
magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), or
other approaches. In some instances, the initial degree of brain reorganization
occurred in parallel with the improvement in spontaneous, real-world use by the
more-affected hand, which suggests that plastic brain changes in some manner
support therapeutic effects. However, the studies are also inconsistent with
respect to whether the reorganization changes occur more in the lesioned vs
unlesioned hemisphere. Interpreting the physiological outcomes post-treatment is
compromised by inconsistencies in study design in the nature of treatment
administered, participant recruitment, imaging modality, and extent of follow-up.
Improved understanding of the biological basis for neuroplasticity in CI therapy
may be obtained through rigorous control of study approaches and through
evaluating treatment changes with more than one modality in the same patients
concurrently. New quantitative structural brain imaging techniques may allow
measuring morphological changes following CI therapy to test hypotheses of
regional brain recruitment in use-dependent therapy while avoiding the
variability of functional imaging and mapping techniques and the difficulties and
assumptions imposed by requiring active limb movement during scanning.
PMID- 17039226
TI - Diffuse large B-cell lymphoma: a heterogeneous group of non-Hodgkin lymphomas
comprising several distinct clinicopathological entities.
AB - Diffuse large B-cell lymphoma (DLBCL) as defined by the World Health Organization
(WHO) classification is clinically, morphologically and genetically a
heterogeneous group of malignant proliferations of large lymphoid B cells. Over
the last 6 years, several studies have been published improving our understanding
of these lymphomas. These studies analyzed DLBCL by their gene expression
profile, provided further information on some of the variants of DLBCL listed in
the WHO classification and stressed the impact of the site of origin of these
tumors. This review summarizes these recent data and explores their impact on the
recognition of new clinicopathological lymphoma entities.
PMID- 17039227
TI - Perforin A91V polymorphism and putative susceptibility to hematological
malignancies.
PMID- 17039229
TI - Transfusions after nonmyeloablative or reduced-intensity conditioning regimens.
PMID- 17039228
TI - Homing, proliferation and survival sites of human leukemia cells in vivo in
immunodeficient mice.
AB - The cellular components of the hematopoietic stem cell niche have been gradually
identified. However, the niche for malignant hematopoiesis remains to be
elucidated. Here, using human leukemia cells, which could be transplanted to
immunodeficient mice, we studied the in vivo homing, proliferation and survival
sites by immunohistopathology, compared with the corresponding sites for cord
blood CD34(+) (CBCD34(+)) cells. The human leukemia cells initially localized on
the surface of osteoblasts in the epiphysial region, and expanded to the inner
vascular and diaphysial regions within 4 weeks. The percentage of CD34(+)
leukemia cells in the bone marrow was transiently increased up to 50%. In vivo 5
bromo-2'-deoxyuridine labeling revealed that the epiphysis was the most active
site for leukemia cell proliferation. CBCD34(+) cells showed the similar pattern
of homing and proliferation to leukemia cells. After high-dose administration of
cytosine-1-beta-D-arabinofuranoside, residual leukemia cells were localized in
the perivascular endothelium as well as in contact with the trabecular endosteum.
These findings suggest that xenotransplantation into immunodeficient mice
provides a useful model to study the leukemia niche.
PMID- 17039230
TI - Eradication of JAK2 V617F mutation after allogeneic transplantation in a patient
with myelofibrosis with myeloid metaplasia.
PMID- 17039231
TI - Molecular pathways in follicular lymphoma.
AB - Follicular lymphoma (FL) is one of the most common B-cell non-Hodgkin's
lymphomas. The initiating genetic event found in approximately 90% of FL is the
t(14;18), causing constitutive expression of the antiapoptotic BCL-2 protein. The
exact secondary alterations leading to full FL development are still poorly
defined. In this review, we address (i) the genetic pathways associated with
tumorigenesis and progression of FL, (ii) the role of micro-environmental factors
with emphasis on B-cell receptor ligands and (iii) lymphoma models in mice and
what they teach us about lymphomagenesis in man.
PMID- 17039232
TI - The downregulation of asparagine synthetase expression can increase the
sensitivity of cells resistant to l-asparaginase.
PMID- 17039233
TI - Antibody-mediated targeting of viral vectors to the Fc receptor expressed on
acute myeloid leukemia cells.
PMID- 17039235
TI - The CCR4 as a novel-specific molecular target for immunotherapy in Hodgkin
lymphoma.
AB - Here, we report that tumor cells from some patients (23.8%) with Hodgkin lymphoma
(HL) are positive for CC chemokine receptor 4 (CCR4). We therefore tested the
chimeric anti-CCR4 monoclonal antibody (mAb), KM2760, the Fc region of which is
defucosylated to enhance antibody-dependent cellular cytotoxicity (ADCC), as a
novel immunotherapy for refractory HL. KM2760 demonstrated a promising antitumor
activity in the CCR4-positive HL-bearing mouse model in the therapeutic setting.
Although KM2760 did not induce any ADCC mediated by mouse natural killer (NK)
cells, it significantly enhanced phagocytosis mediated by mouse
monocytes/macrophages against the CCR4-positive HL cell line in vitro. Together
with the findings that KM2760 did not exhibit any complement-dependent
cytotoxicity or direct antiproliferation activity in vitro, these data indicated
that KM2760 exerted its robust in vivo antitumor activity via
monocytes/macrophages in mice. In the human system, KM2760 enhanced phagocytic
activity mediated by monocytes/macrophages. Furthermore, it induced robust ADCC
mediated by NK cells against the CCR4-positive HL cell line in vitro. Thus, it is
conceivable that KM2760 would have much more potent antitumor activity in humans
than in mice. Collectively, this study strongly indicates that anti-CCR4 mAb
could be a novel treatment modality for patients with CCR4-positive HL.
PMID- 17039234
TI - Allogeneic stem cell transplantation improves the outcome of adults with
t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic
leukemia: results of the prospective multicenter LALA-94 study.
AB - Adult patients with acute lymphoblastic leukemia (ALL) and t(1;19)/E2A-PBX1 or
t(4;11)/MLL-AF4 have a poor outcome. We have evaluated the impact of an
intensified post-remission therapy using a high-dose chemotherapy course followed
by allogeneic or autologous SCT on the outcome of 58 patients with t(1;19)/E2A
PBX1 (E2A group, n=24) or t(4;11)/MLL-AF4 (MLL group, n=34) treated in the LALA
94 multicenter prospective study. Patients in the MLL group had higher WBC counts
and more frequent DIC. CR rates achieved by MLL and E2A groups were similar to
other B-cell ALL (87, 82 and 86% respectively). While in CR, patients with a
donor were assigned to alloSCT (n=22), the remaining patients with were
randomized between autoSCT (n=15) or chemotherapy (n=8). Five-year overall
survival was 31 and 45% for E2A and MLL groups, respectively. In both groups, DFS
was higher in the alloSCT arm as compared to autoSCT and chemotherapy arms. The
results of this study show that chemotherapy intensification did not overcome the
poor prognosis of adults with t(1;19)/E2A-PBX1. Allogeneic SCT should thus be
offered in first CR to patients with t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4. New
therapeutic approaches are needed for patients without donor.
PMID- 17039236
TI - Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying
the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de
Cytogenetique Hematologique.
AB - Recently, we and others described a new chromosomal rearrangement, that is,
inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta)
(7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic
leukemia (T-ALL) patients leading to transcriptional activation of especially
HOXA10. To further address the clinical, immunophenotypical and molecular genetic
findings of this chromosomal aberration, we studied 330 additional T-ALLs. This
revealed TCRbeta-HOXA rearrangements in five additional patients, which brings
the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis
for HOXA10 gene expression was performed in 170 T-ALL patients and detected
HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta
HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10
transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged
cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta
HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations
frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were
not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and
NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In
conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct
cytogenetic subgroup by clinical, immunophenotypical and molecular genetic
characteristics.
PMID- 17039237
TI - Prospective multicentric molecular study for poor prognosis fusion transcripts at
diagnosis in adult B-lineage ALL patients: the LALA 94 experience.
PMID- 17039238
TI - Gene expression profiles of AML derived stem cells; similarity to hematopoietic
stem cells.
AB - Tumors contain a fraction of cancer stem cells that maintain the propagation of
the disease. The CD34(+)CD38(-) cells, isolated from acute myeloid leukemia
(AML), were shown to be enriched leukemic stem cells (LSC). We isolated the
CD34(+)CD38(-) cell fraction from AML and compared their gene expression profiles
to the CD34(+)CD38(+) cell fraction, using microarrays. We found 409 genes that
were at least twofold over- or underexpressed between the two cell populations.
These include underexpression of DNA repair, signal transduction and cell cycle
genes, consistent with the relative quiescence of stem cells, and chromosomal
aberrations and mutations of leukemic cells. Comparison of the LSC expression
data to that of normal hematopoietic stem cells (HSC) revealed that 34% of the
modulated genes are shared by both LSC and HSC, supporting the suggestion that
the LSC originated within the HSC progenitors. We focused on the Notch pathway
since Jagged-2, a Notch ligand was found to be overexpressed in the LSC samples.
We show that DAPT, an inhibitor of gamma-secretase, a protease that is involved
in Jagged and Notch signaling, inhibits LSC growth in colony formation assays.
Identification of additional genes that regulate LSC self-renewal may provide new
targets for therapy.
PMID- 17039239
TI - Stimulation of purinergic receptors modulates chemokine expression in human
keratinocytes.
AB - ATP is abundantly released from stressed or damaged cells in response to
mechanical stimulation, bacteria, or noxious agents. In this study, we have
investigated the possible involvement of P2 receptors (receptor for extracellular
nucleotides) in the expression and release of inflammatory mediators by human
keratinocytes. Notably, extracellular ATP displayed a complex regulation of IFN
gamma-stimulated chemokine expression, with upregulation of CC chemokine ligand 2
(CCL2), CCL5 and CXC chemokine ligand 8 (CXCL8), and suppression of the receptor
CXC chemokine receptor 3 (CXCR3), CXCL9, CXCL10, and CXCL11. The effect of ATP
was mimicked by ADP and adenosine-5'-O-3-thiotriphosphate, whereas 2',3'-O-(4
benzoylbenzoyl) ATP (BzATP) downmodulated all chemokines investigated. UTP had no
effect on IFN-gamma-stimulated chemokine secretion. The broad-spectrum P2
receptor antagonist suramin and the selective P2Y1 inhibitor adenosine 3'
phosphate 5'-phosphosulfate counteracted the effect of ATP on secretion of all
the chemokines examined, whereas pyridoxal phosphate 6-azophenyl 2',4'-disulfonic
acid and KN62 (1-[N,O-bis(5-isoquinoline sulfonyl)-N-methyl-L-tyrosyl] 4
phenylpiperazine) partially prevented the inhibitory effect of ATP on CXCL10
secretion, but on the other hand potentiated the ATP-stimulatory effect on CCL5,
CCL2, and CXCL8 release. In lesional skin of psoriasis and atopic dermatitis
patients, intense P2X7 reactivity was confined to the cell membrane of the basal
layer, whereas diffuse P2Y1 immunostaining was found throughout the epidermis.
Collectively, our data suggest that the orchestrated activation of distinct P2Y
and P2X receptors modulates skin inflammation.
PMID- 17039240
TI - Regulation of NF-kappaB activity and keratinocyte differentiation by the RIP4
protein: implications for cutaneous wound repair.
AB - Receptor-interacting proteins (RIPs) are important regulators of cell
proliferation and differentiation. As RIP4 is a crucial modulator of epidermal
differentiation, we analyzed the expression of different rip genes in healing
skin wounds. Rip4 expression was strongly downregulated in keratinocytes of the
hyperproliferative epithelium at the wound edge early after injury and only
returned to basal levels after completion of wound repair. Rip3 expression was
strongly induced as early as 1 day after wounding. In contrast, rip and rip2
expression remained unaltered. To determine the factors that regulate rip4 gene
expression in keratinocytes, human HaCaT keratinocytes were used as a model
system. We found that scratch wounding as well as treatment with whole serum,
phorbol esters, the growth/differentiation factors epidermal growth factor,
transforming growth factor-beta, and activin A, or the proinflammatory cytokines
tumor necrosis factor-alpha and IL-1beta strongly suppressed rip4 expression in
these cells. In contrast, the steroid dexamethasone and all-trans retinoic acid
slightly stimulated rip4 expression. Suppression of rip4 expression in
keratinocytes using small interfering RNA technology reduced the activation of NF
kappaB, and enhanced the expression of epidermal differentiation markers in these
cells. These data suggest important and unique functions of different RIP
proteins in keratinocytes of normal and wounded skin.
PMID- 17039241
TI - Cytokeratin15-positive basal epithelial cells targeted in graft-versus-host
disease express a constitutive antiapoptotic phenotype.
AB - The normal gene expression profile of rete-tip keratinocytes targeted in human
graft-versus-host disease (GVHD) remains unexplored. Murine lingual epithelium,
unlike murine skin, consists of a basal layer that resembles human cutaneous rete
ridges and harbors rete tip-associated cells that express cytokeratin 15 (K15), a
marker for epithelial stem cells. Target cell apoptosis in murine GVHD
preferentially involves subpopulations of basal cells that (1) reside at tips of
lingual rete ridge-like prominences (RLPs), (2) constitutively express K15
protein, (3) express the proapoptotic protein Bax early in disease progression,
and (4) coincide spatially with putative epithelial stem cells. Here, we show by
real-time reverse transcription-PCR that immunohistochemistry-guided laser
captured K15-positive (K15+) murine basal cells constitutively express
quantitatively higher mRNA levels for K15 but lower mRNA levels of Bax than do
K15- basal cells, consistent with the presumed stem cell nature of K15+ basal
cells. Moreover, apoptosis gene array screening of K15+ microdissected basal
cells demonstrated a dominant trend toward the preferential expression of genes
associated with protection from apoptosis. Accordingly, genes that regulate
apoptotic vulnerability are differentially expressed in basal layer
subpopulations distinguishable by K15 expression.
PMID- 17039242
TI - Altered penetration of polyethylene glycols into uninvolved skin of atopic
dermatitis patients.
AB - Involved regions of the skin in atopic dermatitis (AD) patients have an altered
barrier function. Whether uninvolved skin also has a diminished barrier is
controversial. To assess the barrier function of uninvolved skin in AD patients,
the percutaneous penetration of polyethylene glycols (PEGs) of various molecular
sizes was determined in vivo in AD patients and control subjects using tape
stripping of the stratum corneum (SC). The diffusion and partition coefficients
were determined using Fick's second law of diffusion. The SC thickness was
similar in both groups; however, the trans-epidermal water loss was higher in
atopic skin. The apparent diffusion coefficient of PEGs through atopic skin was
twice as high as through normal skin, and decreased with increasing molecular
weight (MW) in both groups. The partition coefficient in the skin of AD patients
was half of that for normal skin but as for normal skin, there was no MW
dependency. Although atopic skin exhibited altered barrier with respect to
diffusion and partitioning, the permeability coefficients were nearly the same
for atopic and normal skin. The results support the assumption of altered skin
barrier of AD patients even in the skin that is visibly unaffected by disease.
PMID- 17039243
TI - Tissue homing and persistence of defined antigen-specific CD8+ tumor-reactive T
cell clones in long-term melanoma survivors.
AB - Tumor antigen-specific cytotoxic T cells (CTLs) play a major role in the adaptive
immune response to cancers. This CTL response is often insufficient because of
functional impairment, tumor escape mechanisms, or inhibitory tumor
microenvironment. However, little is known about the fate of given tumor-specific
CTL clones in cancer patients. Studies in patients with favorable outcomes may be
very informative. In this longitudinal study, we tracked, quantified, and
characterized functionally defined antigen-specific T-cell clones ex vivo, in
peripheral blood and at tumor sites, in two long-term melanoma survivors. MAGE
A10-specific CD8+ T-cell clones with high avidity to antigenic peptide and tumor
lytic capabilities persisted in peripheral blood over more than 10 years, with
quantitative variations correlating with the clinical course. These clones were
also found in emerging metastases, and, in one patient, circulating clonal T
cells displayed a fully differentiated effector phenotype at the time of relapse.
Longevity, tumor homing, differentiation phenotype, and quantitative adaptation
to the disease phases suggest the contribution of the tracked tumor-reactive
clones in the tumor control of these long-term metastatic survivor patients.
Focusing research on patients with favorable outcomes may help to identify
parameters that are crucial for an efficient antitumor response and to optimize
cancer immunotherapy.
PMID- 17039244
TI - Epidermolysis bullosa simplex in Scotland caused by a spectrum of keratin
mutations.
AB - Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by
mutations in keratins K5 (keratin 5) and K14 (keratin 14), with fragility of
basal keratinocytes leading to epidermal cytolysis and blistering. Patients
present with widely varying severity and are classified in three main subtypes:
EBS Weber-Cockayne (EBS-WC), EBS Kobner (EBS-K), and EBS Dowling-Meara (EBS-DM),
based on distribution and pattern of blisters. We could identify K5/K14 mutations
in 20 out of the 43 families registered as affected by dominant EBS in Scotland;
with previous studies this covers 70% of all Scottish EBS patients, making this
the most comprehensively analyzed EBS population. Nine mutations are novel. All
mutations lie within five previously identified rod domain hotspots and the
severest blistering was associated with mutations in the helix boundary motifs.
In some cases, the same mutation caused symptoms of EBS-WC and/or EBS-K, both
within and between families, suggesting a contribution of additional factors to
the phenotype. In some patients, no mutations were found in K5, K14, or K15,
suggesting involvement of other genes. The results confirm that EBS is best
considered as a single disorder with a spectrum of phenotypic variations, from
severe EBS-DM at one extreme to mild EBS-WC at the other.
PMID- 17039245
TI - Optimized methodology for sequential extraction of RNA and protein from small
human skin biopsies.
AB - Current translational human studies are moving in the direction of concurrent
genomic and proteomic analysis using small clinical samples. Skin tissue,
although easily accessible, is difficult to process owing to its natural
resistance to mechanical shearing and high levels of RNases and proteases.
Currently, these complications result in degraded RNA samples with variable
yield. We have developed a method of sequential extraction of high quality RNA
and protein from a single 3 mm full thickness skin punch biopsy. This method
yields 1-2 microg of RNA and 150 microg of protein, which is usable in many
sensitive downstream applications including microarray, quantitative real-time
PCR, two-dimensional gel electrophoresis and Western blot analysis.
PMID- 17039246
TI - The mitochondrial DNA common deletion is present in most basal and squamous cell
carcinoma samples isolated by laser capture microdissection but generally at
reduced rather than increased levels.
PMID- 17039247
TI - Apoptosis and caspases regulate death and inflammation in sepsis.
AB - Although the prevailing concept has been that mortality in sepsis results from an
unbridled hyper-inflammatory cytokine-mediated response, the failure of more than
30 clinical trials to treat sepsis by controlling this cytokine response requires
a 'rethink' of the molecular mechanism underpinning the development of sepsis. As
we discuss here, remarkable new studies indicate that most deaths from sepsis are
actually the result of a substantially impaired immune response that is due to
extensive death of immune effector cells. Rectification of this apoptotic
inflammatory imbalance using modulators of caspases and other components of the
cell-death pathway have shown striking efficacy in stringent animal models of
sepsis, indicating an entirely novel path forward for the clinical treatment of
human sepsis.
PMID- 17039248
TI - Apoptosis-inducing factor is a major contributor to neuronal loss induced by
neonatal cerebral hypoxia-ischemia.
AB - Nine-day-old harlequin (Hq) mice carrying the hypomorphic apoptosis-inducing
factor (AIF)(Hq) mutation expressed 60% less AIF, 18% less respiratory chain
complex I and 30% less catalase than their wild-type (Wt) littermates. Compared
with Wt, the infarct volume after hypoxia-ischemia (HI) was reduced by 53 and 43%
in male (YX(Hq)) and female (X(Hq)X(Hq)) mice, respectively (P<0.001). The Hq
mutation did not inhibit HI-induced mitochondrial release of cytochrome c or
activation of calpain and caspase-3. The broad-spectrum caspase inhibitor
quinoline-Val-Asp(OMe)-CH(2)-PH (Q-VD-OPh) decreased the activation of all
detectable caspases after HI, both in Wt and Hq mice. Q-VD-OPh reduced the
infarct volume equally in Hq and in Wt mice, and the combination of Hq mutation
and Q-VD-OPh treatment showed an additive neuroprotective effect. Oxidative
stress leading to nitrosylation and lipid peroxidation was more pronounced in
ischemic brain areas from Hq than Wt mice. The antioxidant edaravone decreased
oxidative stress in damaged brains, more pronounced in the Hq mice, and further
reduced brain injury in Hq but not in Wt mice. Thus, two distinct strategies can
enhance the neuroprotection conferred by the Hq mutation, antioxidants,
presumably compensating for a defect in AIF-dependent redox detoxification, and
caspase inhibitors, presumably interrupting a parallel pathway leading to
cellular demise.
PMID- 17039249
TI - Genetic variance modifies apoptosis susceptibility in mature oocytes via
alterations in DNA repair capacity and mitochondrial ultrastructure.
AB - Although the identification of specific genes that regulate apoptosis has been a
topic of intense study, little is known of the role that background genetic
variance plays in modulating cell death. Using germ cells from inbred mouse
strains, we found that apoptosis in mature (metaphase II) oocytes is affected by
genetic background through at least two different mechanisms. The first,
manifested in AKR/J mice, results in genomic instability. This is reflected by
numerous DNA double-strand breaks in freshly isolated oocytes, causing a high
apoptosis susceptibility and impaired embryonic development following
fertilization. Microinjection of Rad51 reduces DNA damage, suppresses apoptosis
and improves embryonic development. The second, manifested in FVB mice, results
in dramatic dimorphisms in mitochondrial ultrastructure. This is correlated with
cytochrome c release and a high apoptosis susceptibility, the latter of which is
suppressed by pyruvate treatment, Smac/DIABLO deficiency, or microinjection of
'normal' mitochondria. Therefore, background genetic variance can profoundly
affect apoptosis in female germ cells by disrupting both genomic DNA and
mitochondrial integrity.
PMID- 17039250
TI - Mitochondrial membrane remodeling in apoptosis: an inside story.
PMID- 17039251
TI - RNA interference-inducing hairpin RNAs in plants act through the viral defence
pathway.
AB - RNA interference (RNAi) is widely used to silence genes in plants and animals. It
operates through the degradation of target mRNA by endonuclease complexes guided
by approximately 21 nucleotide (nt) short interfering RNAs (siRNAs). A similar
process regulates the expression of some developmental genes through
approximately 21 nt microRNAs. Plants have four types of Dicer-like (DCL) enzyme,
each producing small RNAs with different functions. Here, we show that DCL2, DCL3
and DCL4 in Arabidopsis process both replicating viral RNAs and RNAi-inducing
hairpin RNAs (hpRNAs) into 22-, 24- and 21 nt siRNAs, respectively, and that loss
of both DCL2 and DCL4 activities is required to negate RNAi and to release the
plant's repression of viral replication. We also show that hpRNAs, similar to
viral infection, can engender long-distance silencing signals and that hpRNA
induced silencing is suppressed by the expression of a virus-derived suppressor
protein. These findings indicate that hpRNA-mediated RNAi in plants operates
through the viral defence pathway.
PMID- 17039252
TI - DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent
on Cdt2 and Ddb1.
AB - Cdt1 is an essential protein required for licensing of replication origins. Here,
we show that in Schizosaccharomyces pombe, Cdt1 is proteolysed in M and G1 phases
in response to DNA damage and that this mechanism seems to be conserved from
yeast to Metazoa. This degradation does not require Rad3 and Cds1, indicating
that it is independent of classic DNA damage and replication checkpoint pathways.
Damage-induced degradation of Cdt1 is dependent on Cdt2 and Ddb1, which are
components of a Cul4 ubiquitin ligase. We also show that Cdt2 and Ddb1 are needed
for cell-cycle changes in Cdt1 levels in the absence of DNA damage. Cdt2 and Ddb1
have been shown to be involved in the degradation of the Spd1 inhibitor of
ribonucleotide reductase after DNA damage, and we speculate that Cdt1
downregulation might contribute to genome stability by reducing demand on dNTP
pools during DNA repair.
PMID- 17039253
TI - The neurite outgrowth inhibitor Nogo-A promotes denervation in an amyotrophic
lateral sclerosis model.
AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
by motor neuron loss and muscle wasting. In muscles of ALS patients, Nogo-A-a
protein known to inhibit axon regeneration-is ectopically expressed at levels
that correlate with the severity of the clinical symptoms. We now show that the
genetic ablation of Nogo-A extends survival and reduces muscle denervation in a
mouse model of ALS. In turn, overexpression of Nogo-A in wild-type muscle fibres
leads to shrinkage of the postsynapse and retraction of the presynaptic motor
ending. This suggests that the expression of Nogo-A occurring early in ALS
skeletal muscle could cause repulsion and destabilization of the motor nerve
terminals, and subsequent dying back of the axons and motor neurons.
PMID- 17039254
TI - Ca2+ lightning conveys cell-cell contact information inside the cells.
AB - Cells communicate with each other to form organized structures by cell-cell
adhesion and cell-cell repulsion, but it remains to be clarified how cell-cell
contact information is converted into intracellular signals. Here, we show that
cells in contact with neighbouring cells generate local transient intracellular
Ca(2+) signals (Ca(2+) lightning). Ca(2+) lightning was observed near cell-cell
contact regions and was not observed in the central regions of cells or in
solitary cells that were not in contact with other cells. We also show that
Ca(2+) lightning is able to regulate cell-cell repulsion by means of PYK2, a
Ca(2+)-activated protein tyrosine kinase, which induces focal adhesion
disassembly in a Ca(2+)-dependent manner. These results show that cell-cell
contact information might be transmitted by Ca(2+) lightning to regulate
intracellular events.
PMID- 17039256
TI - Aberrant accumulation of PTTG1 induced by a mutated thyroid hormone beta receptor
inhibits mitotic progression.
AB - Overexpression of pituitary tumor-transforming 1 (PTTG1) is associated with
thyroid cancer. We found elevated PTTG1 levels in the thyroid tumors of a mouse
model of follicular thyroid carcinoma (TRbeta(PV/PV) mice). Here we examined the
molecular mechanisms underlying elevated PTTG1 levels and the contribution of
increased PTTG1 to thyroid carcinogenesis. We showed that PTTG1 was physically
associated with thyroid hormone beta receptor (TRbeta) as well as its mutant,
designated PV. Concomitant with thyroid hormone-induced (T3-induced) degradation
of TRbeta, PTTG1 proteins were degraded by the proteasomal machinery, but no such
degradation occurred when PTTG1 was associated with PV. The degradation of
PTTG1/TRbeta was activated by the direct interaction of the liganded TRbeta with
steroid receptor coactivator 3 (SRC-3), which recruits proteasome activator
PA28gamma. PV, which does not bind T3, could not interact directly with SRC
3/PA28gamma to activate proteasome degradation, resulting in elevated PTTG1
levels. The accumulated PTTG1 impeded mitotic progression in cells expressing PV.
Our results unveil what we believe to be a novel mechanism by which PTTG1, an
oncogene, is regulated by the liganded TRbeta. The loss of this regulatory
function in PV led to an aberrant accumulation of PTTG1 disrupting mitotic
progression that could contribute to thyroid carcinogenesis.
PMID- 17039255
TI - Virus-induced type I IFN stimulates generation of immunoproteasomes at the site
of infection.
AB - IFN-gamma is known as the initial and primary inducer of immunoproteasomes during
viral infections. We now report that type I IFN induced the transcription and
translation of immunoproteasome subunits, their incorporation into the proteasome
complex, and the generation of an immunoproteasome-dependent CD8 T cell epitope
in vitro and provide in vivo evidence that this mechanism occurs prior to IFN
gamma responses at the site of viral infection. Type I IFN-mediated generation of
immunoproteasomes was initiated by either poly(I:C) or HCV RNA in human hepatoma
cells and was inhibited by neutralization of type I IFN. In serial liver biopsies
of chimpanzees with acute HCV infection, increases in immunoproteasome subunit
mRNA preceded intrahepatic IFN-gamma responses by several weeks, instead
coinciding with intrahepatic type I IFN responses. Thus, viral RNA-induced innate
immune responses regulate the antigen-processing machinery, which occurs prior to
the detection of IFN-gamma at the site of infection. This mechanism may
contribute to the high effectiveness (95%) of type I IFN-based therapies if
administered early during HCV infection.
PMID- 17039257
TI - Muscular atrophy of caveolin-3-deficient mice is rescued by myostatin inhibition.
AB - Caveolin-3, the muscle-specific isoform of caveolins, plays important roles in
signal transduction. Dominant-negative mutations of the caveolin-3 gene cause
autosomal dominant limb-girdle muscular dystrophy 1C (LGMD1C) with loss of
caveolin-3. However, identification of the precise molecular mechanism leading to
muscular atrophy in caveolin-3-deficient muscle has remained elusive. Myostatin,
a member of the muscle-specific TGF-beta superfamily, negatively regulates
skeletal muscle volume. Here we report that caveolin-3 inhibited myostatin
signaling by suppressing activation of its type I receptor; this was followed by
hypophosphorylation of an intracellular effector, Mad homolog 2 (Smad2), and
decreased downstream transcriptional activity. Loss of caveolin-3 in P104L mutant
caveolin-3 transgenic mice caused muscular atrophy with increase in
phosphorylated Smad2 (p-Smad2) as well as p21 (also known as Cdkn1a), a myostatin
target gene. Introduction of the myostatin prodomain, an inhibitor of myostatin,
by genetic crossing or intraperitoneal administration of the soluble type II
myostatin receptor, another inhibitor, ameliorated muscular atrophy of the mutant
caveolin-3 transgenic mice with suppression of p-Smad2 and p21 levels. These
findings suggest that caveolin-3 normally suppresses the myostatin-mediated
signal, thereby preventing muscular atrophy, and that hyperactivation of
myostatin signaling participates in the pathogenesis of muscular atrophy in a
mouse model of LGMD1C. Myostatin inhibition may be a promising therapy for LGMD1C
patients.
PMID- 17039259
TI - Arterial infections in the new millenium: an old problem revisited.
AB - The natural history of infected aneurysms or arterial infections is characterized
by rapid expansion leading to rupture, pseudoaneurysm formation, and sepsis.
Treatment options include in situ grafting either with prosthetic or autogenous
grafts or with cryopreserved allografts (CPAs), resection of the aneurysm with
remote bypass grafting, and ligation. The purpose of this study was to review our
recent experience with these infections and to present long-term follow-up with
in situ CPAs. From January 2000 through June 2005, we treated nine patients with
infected aneurysms and one patient with an infection without aneurysm formation.
The infection involved the infrarenal abdominal aorta in six patients and the
femoral artery in three patients. One patient had an infected splenic artery
aneurysm. Aortic rupture occurred in five of the six patients with infected
aortas. Two of the three patients with infected femoral aneurysms presented with
recurrent hemorrhage. Of the six patients with aortic infections, five were
treated with in situ CPAs. One patient was treated with aortic resection and
axillofemoral grafting. Two patients with femoral aneurysms were treated with in
situ CPAs, and the third patient underwent aneurysm resection and prosthetic
grafting through the obturator foramen. The patient with the splenic aneurysm
underwent combined valve replacement, aneurysm resection, and splenectomy. Three
of the six patients with aortic infections died postoperatively, all of whom were
septic at presentation. The cause of death in these three patients was multiple
organ failure in two and overwhelming sepsis in one. The three survivors are
alive and well with up to 5-year follow-up. The three patients with infected
femoral aneurysms are alive and well with follow-up extending to 44 months. The
patient with the splenic aneurysm is doing well. No recurrent infections have
been noted among the survivors. The CPAs have remained structurally intact in
all. The mortality rate among patients with abdominal aortic infections remains
high and is likely related to their preoperative septic state. In situ grafting
with CPAs appears to be a reasonable treatment option for arterial infections.
CPAs appear to maintain their structural integrity and to be resistant to
recurrent infection.
PMID- 17039258
TI - NF-kappaB2 is required for the establishment of central tolerance through an Aire
dependent pathway.
AB - NF-kappaB2-deficient mice have impaired T and B cell responses. We found,
however, that in these mice there was severe infiltration of lymphocytes into
multiple organs and increased activity of autoantibodies to peripheral tissue
antigens in a manner similar to that of autoimmune regulator-deficient (Aire
deficient) mice. We further demonstrated that NF-kappaB2 was required for thymic
Aire gene transcriptional regulation. The Nfkb2(-/-) thymus had distinct cortical
and medullar structures, but reduced Aire and target gene expression of
peripheral tissue antigens. Engraftment of Nfkb2(-/-) thymic stroma to nude mice
recapitulated the autoimmune phenotype of the native Nfkb2(-/-) mice, confirming
a key defect in central tolerance. Lymphotoxin beta receptor (LTbetaR) ligation
induced Aire gene expression was also largely abolished in the absence of NF
kappaB2. Thus NF-kappaB2 downstream of LTbetaR plays an important role in the
regulation of central tolerance in an Aire-dependent manner.
PMID- 17039260
TI - SAA1 alpha/alpha alleles in Behcet's disease related amyloidosis.
AB - Behcet's disease (BD) related amyloidosis is relatively rare. Serum amyloid A
protein (SAA) protein gene polymorphism is one of the factors implicated in the
pathogenesis of AA type amyloidosis. The aim of this study is to investigate SAA1
gene polymorphism in different patient groups: (1) BD related amyloidosis, (2) BD
without amyloidosis, and (3) healthy controls. One hundred eleven patients from
three main groups were included in the study: (1) BD related amyloidosis (n = 9),
(2) BD without amyloidosis (n = 39), and (3) healthy controls (n = 63).
Homozygous alpha/alpha is present in 78% of patients with BD and amyloidosis. The
SAA1 alpha/alpha genotype is significantly more common among patients with BD and
amyloidosis. This study demonstrated increased frequency of alpha/alpha genotype
in BD related amyloidosis. To our knowledge, the relationship between alpha/alpha
genotype and BD related amyloidosis was not studied previously. In conclusion,
the SAA1 alpha/alpha genotype is a risk factor for amyloidosis in BD.
PMID- 17039261
TI - Successful treatment of life-threatening intestinal ulcer in Behcet's disease
with infliximab: rapid healing of Behcet's ulcer with infliximab.
AB - Behcet's disease is a chronic, relapsing, multisystem inflammatory disorder
characterized predominantly by recurrent orogenital ulcers, skin involvement, and
uveitis. Recurrent mucocutaneous lesions may be the only symptom in mild cases,
but ocular, gastrointestinal, and central nervous system involvement may occur in
severe cases. We report in this study the successful treatment with infliximab of
severe life-threatening GI bleeding caused by an ileal ulcer in a patient with
Behcet's disease. Antitumor necrosis factor (TNF) therapy could be an emergency
therapeutic option in patients with massively bleeding Behcet's disease and
unstable patients or those with acute bleeding with other TNF-alpha-mediated
autoimmune diseases. Another option for anti-TNF therapy could be as bridging
management between conservative and surgical treatment.
PMID- 17039262
TI - Laser speckle imaging of dynamic changes in flow during photodynamic therapy.
AB - We present a study investigating the use of laser speckle imaging (LSI) for
monitoring blood flow during photodynamic therapy (PDT) utilizing the therapeutic
illumination radiation. The coherent nature of a laser source, often used in PDT,
offers the possibility of obtaining information on the blood flow without
interrupting treatment. We have found that in the rat skin-fold observation
chamber, it is possible to monitor the vasculature response to PDT in individual
arteries, veins and in tumour microvasculature with significantly higher spatial
and temporal resolution than current methods. This illustrates the potential for
LSI for monitoring PDT, in particular for vascular-localizing photosensitizers,
where current non-invasive methods are difficult because of high absorption due
to blood and the specific localization of photosensitizer within the vasculature.
However, critical problems need to be further investigated and solved, like the
influence of tissue sampling volume, changing of optical properties and movement
artefacts from other vessels on the LSI signal. Until then, the real potential of
LSI for monitoring blood flow remains of limited value.
PMID- 17039263
TI - Hormonal therapy for postmenopausal breast cancer: the science of sequencing.
AB - Oestrogens play important roles in the natural history of breast cancer.
Consequently, therapies have been developed to reduce oestrogen levels or to
block signalling through oestrogen receptors (ER). These therapies include
tamoxifen, selective oestrogen receptor modulators (SERMs), aromatase inhibitors
(AIs) and selective oestrogen receptor downregulators (SERDs). All have proven
clinical efficacy in postmenopausal women with ER-positive breast cancer and can
be effective in the neoadjuvant and adjuvant settings, and in the management of
advanced disease. This range of endocrine therapies offers the opportunity for
prolonging benefit from treatment and delaying tumour recurrence/progression by
combining the different classes of drugs or by using them sequentially.
Evaluation of the potential clinical benefits of concomitant or sequential
endocrine therapies should be based on considerations of efficacy and safety
profiles, mechanisms of action/resistance and effects on tumour biology. Evidence
from preclinical models and from randomized clinical trials in patients with
postmenopausal breast cancer suggests that concomitant endocrine therapies are no
more effective than AIs alone. However, using AIs either as initial therapy or
sequentially after tamoxifen appears to produce more benefits beyond the use of
tamoxifen alone.Currently, there are no proven algorithms for the planned,
sequential use of the full range of endocrine therapies, particularly for the
majority of patients who present with early breast cancer. Prospective,
randomized clinical trials are needed to determine the best use of therapies in
particular settings, taking into account the spectrum of molecular phenotypes in
different tumours.
PMID- 17039264
TI - Role of single nucleotide polymorphisms and haplotypes in BRCA1 in breast cancer:
Czech case-control study.
AB - We aimed at determining whether any association exists between six single
nucleotide polymorphisms in breast cancer associated gene (BRCA1) and the risk of
breast cancer. We constructed haplotypes and analyzed their importance as well.
Clinico-pathological characteristics of breast cancer patients were included in
the study to evaluate the prognostic impact of BRCA1 polymorphisms and
haplotypes. Polymerase chain reaction-restriction fragment length polymorphism
based genotyping assays were used to determine the frequency of polymorphisms in
codons 356, 871, 1038, 1183, 1436, and 1613 of BRCA1 in a group of 306 incident
breast cancer patients and 313 unaffected controls of Czech origin. Statistical
analyses revealed that the BRCA1 Arg356 allele may play a protective role in
breast cancer (age-adjusted OR = 0.61, CI = 0.39-0.94, p = 0.026). We also
observed a significant correlation between polymorphism Gln356Arg and stage (p =
0.026) in premenopausal cases suggesting that carriers of the wild Gln356Gln
allele are at significantly higher risk of advanced disease. The most common
haplotypes of BRCA1 did not play a significant role in breast cancer either as
risk factors or as prognostic factors. The study on rare BRCA1 haplotypes however
should be repeated using larger groups. In conclusion, the BRCA1-Gln356 allele
presents risk factor in the onset and progression of breast cancer in Czech
population and its use as a possible screening tool should be considered.
PMID- 17039265
TI - Predicting response to primary chemotherapy: gene expression profiling of
paraffin-embedded core biopsy tissue.
AB - PURPOSE: Primary chemotherapy provides an ideal opportunity to correlate gene
expression with response to treatment. We used paraffin-embedded core biopsies
from a completed phase II trial to identify genes that correlate with response to
primary chemotherapy. PATIENTS AND METHODS: Patients with newly diagnosed stage
II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks
x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned.
Pretreatment core biopsy samples were interrogated for genes that might correlate
with pathologic complete response (pCR). In addition to the individual genes, the
correlation of the Oncotype DX Recurrence Score with pCR was examined. RESULTS:
Of 70 patients enrolled in the parent trial, core biopsies samples with
sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had
inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two
of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes
correlating with pCR could be grouped into three large clusters: angiogenesis
related genes, proliferation related genes, and invasion-related genes.
Expression of estrogen receptor (ER)-related genes and Recurrence Score did not
correlate with pCR. In an exploratory analysis we compared gene expression in IBC
to non-inflammatory breast cancer; twenty-four (9%) of the genes were
differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated
in IBC. CONCLUSION: Gene expression analysis on core biopsy samples is feasible
and identifies candidate genes that correlate with pCR to primary chemotherapy.
Gene expression in IBC differs significantly from noninflammatory breast cancer.
PMID- 17039266
TI - Breast cancer patients on adjuvant chemotherapy report a wide range of problems
not identified by health-care staff.
AB - BACKGROUND: Adjuvant chemotherapy for primary breast cancer is associated with
significant side effects. The aims of this study were (1) to compare health
related quality of life (HRQL) in patients undergoing adjuvant chemotherapy to
patients not on chemotherapy and (2) to compare these results against a survey
investigating health-care professionals' knowledge of HRQL. METHODS: Patients on
adjuvant cyclophosphamide, methotrexate, fluoracil chemotherapy were compared to
'low-risk' patients not on chemotherapy ('control group'). A questionnaire
including the EORTC QLQ-C30, the Hospital Anxiety and Depression Scale (HADS),
and the DBCG 89 Questionnaire was administered six times during a 2-year period.
Forty-six experienced health-care professionals were asked which quality-of-life
issues they thought were affected by adjuvant chemotherapy. RESULTS: After 2
years, 159 of 242 patients on chemotherapy and 148 of 199 patients in the control
group were alive and recurrence-free and had completed all questionnaires. Worse
HRQL during chemotherapy was seen, as had been previously suggested, for 23 of 30
variables. A number of the health-care professionals had not indicated patients
to have these side effects. Several side effects persisted after the
chemotherapy. CONCLUSIONS: This study provides the most comprehensive description
of HRQL in adjuvant therapy to date. The discrepancy between patients and
doctors/nurses suggests that patients have been insufficiently informed about the
impact of chemotherapy on quality of life. The results of this study provide a
basis for information that can be given to patients, and indicate that the care
offered to patients in chemotherapy should seek to prevent, identify, and
alleviate a very broad range of problems.
PMID- 17039267
TI - A prospective study of adjuvant CMF in males with node positive breast cancer: 20
year follow-up.
AB - PURPOSE: To determine the long-term overall survival of male patients with stage
II node positive breast cancer treated with adjuvant chemotherapy. PATIENTS AND
METHODS: Between 1974 and 1988, 31 male breast cancer patients were prospectively
enrolled on study MB-82 in the National Cancer Institute. Following mastectomy,
patients were treated with 12 cycles of cyclophosphamide, methotrexate, and
fluorouracil (CMF) chemotherapy. RESULTS: Median patient age was 61 years (38-74
years). Twenty-one patients (68%) had 1-3 positive axillary lymph nodes while ten
patients (32%) had four or more positive nodes. Estrogen receptor status was
positive in 22 (71%), negative in 1 (3%), and unknown in 8 (26%) tumors.
Progesterone receptor status was positive in 18 (58%), negative in 3 (10%), and
unknown in 10 (32%) tumors. Median potential follow-up for all patients is 22.5
years with a median survival of 16.3 years. Twenty-one of 31 patients have died;
one from a treatment-related complication, nine patients from recurrent breast
cancer, five from other cancers, one from non-cancer related causes, and five
from unknown causes. Ten patients remain alive at a median of 19.2 years. The
overall survival probability at 10 years is 64.5% (95% CI: 46.9-78.9%), at 15
years is 51.6% (95% CI: 34.8-68%), and at 20 years is 42.4% (95% CI: 25.8-60.8%).
CONCLUSION: To our knowledge, 20-year prospective data with adjuvant chemotherapy
in male breast cancer has never been reported. Adjuvant chemotherapy may benefit
male breast cancer patients with positive nodes.
PMID- 17039268
TI - Gene expression profiling of breast cancer cells in response to gemcitabine: NF
kappaB pathway activation as a potential mechanism of resistance.
AB - Gemcitabine is a nucleoside analog with clinical relevance in the treatment of
several solid tumors, including breast carcinoma. In spite of its cytotoxic
effect, clinical efficacy is impaired by the development of resistance. We
performed gene expression analysis to shed light into the molecular mechanism of
action of this drug in two breast cancer cell lines. Activation of genes related
with cell cycle, cell growth and apoptosis (BNIP3L, CCNG2, DDIT4, TGFB2, TP53BP1,
TP53INP1, and VEGF) was the main finding in the p53-wild type cell line MCF7,
while the p53-non-functional cell line MDA-MB-231 was characterized by the
regulation of NF-kappaB target genes (BIRC3, CXCL1/GRO1, IRAK2, TNF, TNFAIP and
TRAF1). Genes consistently induced (ATF3, CCNG2, CDKN1A, EGR1, INSIG1, and MAF)
or repressed (CCND1 and VGF) in both cell lines, were also found after
gemcitabine treatment. In addition, MDA-MB-231 cells showed a higher basal and
induced NF-kappaB transcriptional activity after treatment with gemcitabine. In
comparison with gemcitabine, gene expression after 5-fluorouracil treatment
showed essentially different profiles in both cell lines. This, in spite of using
equitoxic concentrations producing similar effects on cell cycle. NF-kappaB
transcriptional activity in MDA-MB-231 cells was dependent on IkappaB-alpha
phosphorylation, as shown by functional experiments using the specific inhibitor
BAY11-7082. Moreover, immunohistochemical analysis of clinical samples of breast
carcinoma further validated the induction of NF-kappaB expression and IkappaB
down-regulation upon neoadjuvant gemcitabine treatment. Thus, gene expression
patterns, in vitro functional studies and analysis of tissue samples are in
agreement with a role for NF-kappaB pathway in gemcitabine response. Together
with the reported role for NF-kappaB in the induction of resistance to
chemotherapy, our data gives support to clinical strategies combining gemcitabine
with NF-kappaB inhibitors in breast cancer.
PMID- 17039269
TI - Very high incidence of familial colorectal cancer in Newfoundland: a comparison
with Ontario and 13 other population-based studies.
AB - Newfoundland has the highest rate of colorectal cancer (CRC) of any Canadian
province. In order to investigate the factors, especially genetic components,
responsible for CRC we established the Newfoundland Colorectal Cancer Registry.
In a 5-year period we examined every case of CRC diagnosed under the age of 75
years and obtained consent from 730 cases. Careful analysis of family history was
used to assign a familial cancer risk, based on established criteria. We observed
that 3.7% of CRC cases came from families meeting the Amsterdam II criteria and a
further 0.9% of cases involved familial adenomatous polyposis (FAP). An
additional 43% of cases met one or more of the revised Bethesda criteria and 31%
of all cases had a first-degree relative affected with CRC. We compared the
Newfoundland data with data from the province of Ontario, where the same
recruitment and risk-assessment criteria were used. In all categories, the
indicators of familial risk were significantly higher in Newfoundland. These data
were also compared to results published from 13 other population-based studies
worldwide. In every category the proportion of Newfoundland cases meeting the
criteria was higher than in any other population. The mean differences were: 3.5
fold greater for FAP, 2.8-fold higher for Amsterdam criteria, 2.0-fold higher for
Bethesda criteria and 1.9-fold higher for the number of affected first-degree
relatives. We conclude that the high incidence of CRC in Newfoundland may be
attributable to genetic, or at least familial, factors. In the high-risk families
we provide evidence for the involvement of founder mutations in the APC and MSH2
genes.
PMID- 17039270
TI - The natural history of a combined defect in MSH6 and MUTYH in a HNPCC family.
AB - In the inherited syndromes, MUTYH-associated polyposis (MAP) and hereditary
nonpolyposis colorectal cancer (HNPCC), somatic mutations occur due to loss of
the caretaker function that base-repair (BER) and mismatch repair (MMR) genes
have, respectively. Recently, we identified a large branch from a MSH6 HNPCC
family in which 19 family members are heterozygous or compound heterozygous for
MUTYH germ line mutations. MSH6/MUTYH heterozygote mutation carriers display a
predominant HNPCC molecular tumour phenotype, with microsatellite instability and
underrepresentation of G>T transversions. A single unique patient is carrier of
the MSH6 germline mutation and is compound heterozygote for MUTYH. Unexpectedly,
this patient has an extremely mild clinical phenotype with sofar only few
adenomas at age 56. Four out of five adenomas show characteristic G>T
transversions in APC and/or KRAS2, as seen in MUTYH associated polyposis. No
second hit of MSH6 is apparent in any of the adenomas, due to retained MSH6
nuclear expression and a lack of microsatellite instability. Although this
concerns only one case, we argue that the chance to find an additional one is
extremely small and currently a mouse model with this genotype combination is not
available. Moreover, the patients brother who is also compound heterozygous for
MUTYH but lacks the MSH6 germline mutation presented with a full blown polyposis
coli. In conclusion, these data would support the notion that abrogation of both
MSH6 DNA mismatch repair and base repair might be mutually exclusive in humans.
PMID- 17039272
TI - A simple polymerase chain reaction-sequencing analysis capable of identifying
multiple medically relevant filamentous fungal species.
AB - Due to the accumulating evidence that suggests that numerous unhealthy conditions
in the indoor environment are the result of abnormal growth of the filamentous
fungi (mold) in and on building surfaces it is necessary to accurately determine
the organisms responsible for these maladies and to identify them in an accurate
and timely manner. Historically, identification of filamentous fungal (mold)
species has been based on morphological characteristics, both macroscopic and
microscopic. These methods may often be time consuming and inaccurate,
necessitating the development of identification protocols that are rapid,
sensitive, and precise. To this end, we have devised a simple PAN-PCR approach
which when coupled to cloning and sequencing of the clones allows for the
unambiguous identification of multiple fungal organisms. Universal primers are
used to amplify ribosomal DNA sequences which are then cloned and transformed
into Escherichia coli. Individual clones are then sequenced and individual
sequences analyzed and organisms identified. Using this method we were capable of
identifying Stachybotrys chartarum, Penicillium purpurogenum, Aspergillus
sydowii, and Cladosporium cladosporioides from a mixed culture. This method was
found to be rapid, highly specific, easy to perform, and cost effective.
PMID- 17039271
TI - The phenotypic expression of three MSH2 mutations in large Newfoundland families
with Lynch syndrome.
AB - To compare the phenotypic expression of three different MSH2 mutations causing
Lynch syndrome, 290 family members at 50% risk of inheriting a mutation were
studied. Two truncating mutations of the MSH2 gene have been identified in
Newfoundland: an exon 8 deletion in five families (N=74 carriers) and an exon 4
16 deletion in one family (N=65 carriers). The third mutation was an intron 5
splice site mutation resulting in deletion of exon 5 in RNA and occurred in 12
families (N=151 carriers). Age to onset of first cancer, first colorectal cancer
(CRC), first extracolonic cancers and death were compared. By age 60, 89% of
family members with the intron 5 mutation, 81% with the exon 8 deletion, and 85%
with the exon 4-16 deletion had developed cancer. For all three mutations males
had a higher age-related risk of CRC and death compared to females. In the intron
5 splice site mutation carriers, the number of transitional cell cancers of the
urinary tract was significantly lower and time to first ovarian cancer was
significantly higher than in the carriers of the genomic deletions. The incidence
of CRC in MSH2 mutation carriers, exposed to the same environment, is not
modified by the specific mutation, although there is a suggestion that type of
mutation may influence development of some extracolonic cancers.
PMID- 17039273
TI - Genotyping by RAPD-PCR analyses of Malassezia furfur strains from pityriasis
versicolor and seborrhoeic dermatitis patients.
AB - Malassezia furfur is lypophilic yeast commonly associate with dermatological
disorders. In the present work, we described the isolation of 47 M. furfur
strains from three groups of patients: pityriasis versicolor (21 isolates),
seborrhoeic dermatitis (15 isolates) and seborrhoeic dermatitis of the HIV
positive patients (11 isolates). To investigate the identity of the strains at
molecular level, DNA genomic of M. furfur strains were prepared and used to RAPD
PCR analyses. RAPD assay were carried out using two decamer primers and bands
pattern generated were analyzed by an Unweighted Pair-Group Method (UPGMA).
Dendrogram established a distinct differentiation between M. furfur isolates from
pityriasis versicolor and seborrhoeic dermatitis patients with or without AIDS.
We concluded that RAPD typing presented a high discriminatory power between
strains studied in this work and can be applied in epidemiological investigation
of skin disease causing by M. furfur.
PMID- 17039274
TI - Majority of Actinomadura clinical isolates from sputa or bronchoalveolar lavage
fluid in Japan belongs to the cluster of Actinomadura cremea and Actinomadura
nitritigenes, and the description of Actinomadura chibensis sp. nov.
AB - In Japan during 1996-2004, 21 actinomycete strains that have madurose as the
diagnostic cell-wall sugar and show true branching in their substrate and aerial
mycelia were isolated from sputa or bronchoalveolar lavage (BAL) fluid of
patients with pulmonary infections or who were suspected of having related
infections. Chemotaxonomic studies showed that all the isolates belong to the
genus Actinomadura. Among them, six and seven strains were classified
respectively into clusters of Actinomadura nitritigenes and Actinomadura cremea
based on 16S rDNA analyses because their 16S rDNA similarities to those
respective species were greater than 99.5%. To our knowledge, this is first
report that strains of above two species were isolated from clinical specimens.
Neither Actinomadura madurae nor Actinomadura pelletieri strain was isolated, and
one new species, Actinomadura chibensis, was proposed; the remaining seven
strains were not assigned into any known species, suggesting the presence of
another new Actinomadura species.
PMID- 17039275
TI - Saksenaea vasiformis infections: case report and literature review.
AB - Since the first human infection by Saksenaea vasiformis in 1976 another 26 cases
have been reported. Here is a report of a new case which involved an Ecuadorian
adolescent who suffered serious burns after a car accident. It developed as a
localized cutaneous infection which was successfully treated with surgical
debridement and amphotericin B. This is the second report of this infection from
South America and the third involving a burn patient. The previously reported 27
cases are reviewed.
PMID- 17039276
TI - A case of recurrent episodes of Candida parapsilosis fungemia.
AB - Candida species is the fourth most commonly isolated organism in blood stream
infections in the hospital setting. Patients with candidemia frequently succumb
to this infection. For those that survive an initial candidemia, an increasing
number of cases of breakthrough or recurrent candidemias have been reported in
the literature. We report three episodes of C. parapsilosis fungemia in a cancer
patient. Molecular testing was performed and confirmed that all these episodes
occurring within an eight-month period were caused by the same organism. The
incidence of recurrent candidemia is likely to increase in the near future.
Studies and therapeutic interventions for patients at risk for recurrent
candidemias are warranted.
PMID- 17039277
TI - Resistant Microascus cirrosus pneumonia can be treated with a combination of
surgery, multiple anti-fungal agents and a growth factor.
AB - A 49-year old male with acute myelogenous leukemia relapsed eight years post
allogeneic bone marrow transplantation. The patient received induction
chemotherapy causing prolonged neutropenia. The patient developed pneumonia for
which empirical antibacterial and antifungal therapy were started. The patient
underwent a video-assisted thorocascopy with near complete resection of the
lesion because of poor response to treatment. Microascus cirrosus was identified
in the tissue. In vitro susceptibility test to different antifungal agents showed
M. cirrosus was very resistant. The patient is undergoing second allogeneic
transplant with improved pneumonia resulting from a combination of treatment for
fungal infection, which included surgery, antifungal agents, and granulocyte
colony stimulating factor. The Microascus genus rarely causes invasive fungal
infection in humans and can be very difficult to treat because of the resistance
to available antifungal agents.
PMID- 17039278
TI - Keratinophilic fungi from the vicinity of meteorite crater soils of Lonar
(India).
AB - Thirty-two soil samples were collected from six sites in the vicinity of Lonar
lake, a meteorite crater and screened for presence of keratinophilic fungi using
hair baiting techniques for isolation. Seventeen isolates were recovered and
identified. The cultures were identified by recognition of their macro- and
micromorphological features. Their identification was also confirmed by the BLAST
search of sequences of ITS1-5.8S-ITS2 rDNA region against the NCBI/Gene bank data
and compared with deposited sequences for identification purpose. Seven species
of four genera were isolated viz. Aphanoascus durus (9.38%), Aphanoascus punsolae
(3.125%), Auxarthron kuehnii (3.125%), Chrysosporium indicum (25.00%),
Chrysosporium tropicum (3.125%), Chrysosporium sp. (3.125%), Chrysosporium state
of Ctenomyces serratus (6.25%).
PMID- 17039279
TI - Reduction of aflatoxin B1 in chicken feed by using Saccharomyces cerevisiae,
Rhizopus oligosporus and their combination.
AB - Aflatoxin B1 is a toxigenic and carcinogenic compound produced by Aspergillus
flavus and Aspergillus parasiticus. An approach to prevent aflatoxin
contamination in feed was carried out by using Saccharomyces cerevisiae (Sc) and
Rhizopus oligosporus (Ro). Aspergillus flavus was cultured together with Sc, Ro
and their combination (ScRo) in chicken feed. The aflatoxin B1 content was
observed at day 0, 5, 10 and 15. The result showed that aflatoxin B1
contaminations in feed were reduced by Sc, Ro and ScRo addition. The highest
reduction of aflatoxin B1 content was shown at day 5 for all treatments with Sc,
Ro and ScRo. The best activity of reducing aflatoxin B1 was shown by Ro. Although
the ability of reducing aflatoxin B1 of Sc, Ro or ScRo was not significantly
different, Sc or Ro gave the better result than ScRo and they are better used
individually.
PMID- 17039280
TI - Mycocin production in Pseudozyma tsukubaensis.
AB - Killer activity expressed at pH values ranging from 3.5 to 6.0 was found in the
ustilaginaceous yeast-like species, Pseudozyma tsukubaensis. Its killer phenotype
was incurable, and extrachromosomal genetic elements were not detected. The toxin
excreted with a molecular mass above 15 kDa is fungicidal, resistant to
proteolytic cleavage, thermolabile and active only against fungi within the
Ustilaginomycetes (the orders Microstromatales and Ustilaginales).
PMID- 17039281
TI - Fosinopril and carvedilol reverse hypertrophy and change the levels of protein
kinase C epsilon and components of its signaling complex.
AB - OBJECTIVE: To demonstrate the alterations of Protein Kinase C epsilon (PKC
epsilon) and components of its signaling complexes after treatment with
fosinopril and carvedilol and analyze potential molecular mechanisms of the two
drugs for cardiac hypertrophy and heart failure. METHODS: Pressure-overload
cardiac hypertrophy (POH) was developed in 8-week-old male Sprague Dawley rats by
abdominal aortic banding. The rats were divided into three groups at the age of
20 weeks: POH without failure group, reversed POH with drugs group, and POH with
failure group on high diet. Western Blot analysis, co-immunoprecipitation and
proteomic analysis were performed in ventricular tissues of rat hearts. RESULTS:
Increased PKC epsilon was found during POH. PKC epsilon decreased during
transition from POH to heart failure (HF). However, increased PKC epsilon
inclined to recover to normal levels after treatment with both drugs. There were
differential proteins in PKC epsilon complexes during the different stages of
POH. The two significant PKC epsilon-binding proteins, MAD1 and Lyn A, were only
present in PKC epsilon complex during reversing POH with drugs. CONCLUSION:
Chronic administration of carvedilol and fosinopril could reverse the development
of POH and delay the appearance of HF, partly by regulating PKC epsilon level and
its signaling complex. MAD1 and Lyn A may be important proteins participating in
the reversing process.
PMID- 17039282
TI - RBx 7,796: A novel inhibitor of 5-lipoxygenase.
AB - OBJECTIVE: To evaluate the pharmacological profile of RBx 7,796, a novel 5
lipoxygenase inhibitor. MATERIALS AND METHODS: RBx 7,796 was evaluated for 5-
lipoxygenase inhibitory potential using human recombinant enzyme and profiled for
selectivity against 12 and 15 lipoxygenase. RBx 7,796 was evaluated in cell based
assay for inhibition of A23,187 induced LTB(4) release from isolated neutrophils.
Ex vivo activity was evaluated for inhibition of A23,187 induced LTB(4) release
in blood from treated rats. In vivo efficacy of RBx 7,796 was profiled in LPS
induced neutrophilia model in rats and also in ovalbumin induced
bronchoconstriction and airway inflammation models in guinea pigs. RESULTS: RBx
7,796, a novel chemotype, showed competitive inhibition of 5-lipoxygenase enzyme
with an IC(50) of 3.5 +/- 1.1 microM. RBx 7,796 offered >100 fold selectivity
against other related enzymes - 12 and 15 lipoxygenase. RBx 7,796 inhibited
release of LTB(4) from human and rat neutrophils in vitro. Upon administration to
rats, RBx 7,796 inhibited A23,187 induced LTB(4) release from rat neutrophils.
Upon repeated administration, dosed once daily, RBx 7,796 inhibited LPS induced
neutrophil influx in rat airway. RBx 7,796 also inhibited allergen induced
bronchoconstriction and eosinophil influx in guinea pig airway in a dose
dependent manner. CONCLUSION: The results suggest that RBx 7,796, a novel
chemotype, is an orally efficacious inhibitor of 5-lipoxygenase enzyme that is
effective against both neutrophilic and eosinophilic airway inflammation and
shows potent inhibition with once daily administration.
PMID- 17039283
TI - Transforming growth factor-beta stimulates IL-1beta-induced monocyte
chemoattractant protein-1 expression in human synovial cells via the ERK/AP-1
pathway.
AB - OBJECTIVE AND DESIGN: Transforming growth factor- beta (TGF-beta) has not only a
fibrogenic role, but also monocyte/ macrophage chemotactic properties in a
synovial joint. However, little is known about the effects of TGF-beta on
monocyte chemoattractant protein-1 (MCP-1) expression in human synovial cells
under inflammatory status. The aim of this study was to determine whether TGF
modulates MCP-1 production under the chronic inflammation, and to elucidate the
cell signaling mechanism involved. MATERIALS AND METHODS: Human synovial cells
were exposed to IL-1beta, which mimics the environment of chronic inflammation.
Production of MCP-1 protein and expression of MCP-1 mRNA were determined by ELISA
and real-time PCR. RESULTS: TGF-beta upregulated the expression of MCP-1 mRNA and
protein with or without IL-1beta. TGF-beta and IL-1beta synergistically enhanced
MCP-1 gene expression, and an AP-1 binding site was involved in the signal
transduction. In addition, MEK inhibitor completely suppressed TGF-beta-induced
MCP-1 production. CONCLUSIONS: TGF-beta and IL-1beta synergistically enhance MCP
1 gene expression through the activation of the MEK/ERK1/2 pathways, which leads
to AP-1 activation. The impairment of MCP-1 regulation by TGF-beta in resident
synovial cells might represent an important mechanism of chronic inflammation and
tissue fibrosis in a synovial joint. MCP-1 should be considered a valid target
for therapeutic intervention.
PMID- 17039284
TI - Concentrations of CXCL8, CXCL9 and sTNFR1 in plasma of patients with pulmonary
tuberculosis undergoing treatment.
AB - BACKGROUND: Chemokines are a class of cytokines with chemotactic properties shown
to be induced by M. tuberculosis or its antigens in vitro and in experimental
infection in vivo. A few studies have also demonstrated the expression of
chemokines in clinical samples of patients with active tuberculosis (TB). In the
present work, we measured the concentration of chemokines in plasma samples of
HIV-negative patients with pulmonary tuberculosis at different stages of
chemotherapy. For comparison, we also evaluated the levels of sTNFR1 and TNF
alpha. METHODS: Cytokines and chemokines were measured by ELISA in healthy
individuals and patients with active pulmonary TB at different stages of
treatment. RESULTS: The concentrations of CXCL8, CXCL9 and sTNFR1 were elevated
in patients with active pulmonary TB but returned to background levels at 4-6
months of chemotherapy. The concentration of CCL11 was elevated in patients with
active pulmonary tuberculosis when compared to control and remained elevated
throughout the specific therapy. There was no difference in the plasma
concentration of CCL2 and CXCL10 between pulmonary TB patients and control
subjects. CONCLUSION: Measurement of the CXCL8, CXCL9 and sTNFR1 may be useful to
assess response to treatment in pulmonary TB patients.
PMID- 17039285
TI - Effect of sesamin on serum cholesterol and triglycerides levels in LDL receptor
deficient mice.
AB - BACKGROUND: Sesamin, a major lignan from sesame seeds has been associated with
cholesterol reduction in previous reports, but recent studies suggested
differences in the response to sesamin intake depending on the model studied as
well as the nature of the sesamin preparation used. AIM: The effect of pure
sesamin epimer on serum lipids was studied in hypercholesterolemic LDL receptor
knockout mice under cholesterol fed condition. DESIGN: Animals were randomly
assigned to 4 groups, fed an atherogenic diet containing stanol ester, sesamin,
combination of stanol ester and sesamin or a control diet with no additions.
RESULTS: The control group showed an almost 3-fold increase in serum cholesterol
levels due to the atherogenic diet but no effect was seen for triglyceride
levels. Stanol ester alone or together with sesamin significantly attenuated the
elevation of the cholesterol levels. CONCLUSION: Sesamin alone did not affect the
elevation of the diet-induced cholesterol level and it did not enhance the effect
of stanol ester.
PMID- 17039286
TI - [Quality of health care of the elderly].
PMID- 17039287
TI - Health care in seniority: crucial questions and challenges from the perspective
of health services research.
AB - This paper gives an updated outlook on geriatric health care in Germany and on
research demands with particular respect to advanced-age patients with
multimorbidity. The paper is written from the perspective of health services
research and addresses selected topics such as primary care, palliative care,
health policies and patient orientation. It is pointed out that the structure of
services and processes of health care delivery is not compatible with the complex
demands of the target group, and that the priorities of improvement strategies
may differ among the various professional groups involved (e. g. primary care
physicians as generalists and palliative and geriatric experts as specialists).
Furthermore, it is argued that the current incentives for establishing integrated
health care may not be adequate to ensure that sustainable changes are made in
the long term.
PMID- 17039288
TI - [Psychopharmacological drug treatment in Munich nursing homes].
AB - The survey of Munich nursing homes with 888 residents showed that 56.4% received
psychotropic drugs and a twice as frequent prescription of antipsychotics to
residents of double rooms than of single rooms. In a subsample of 397 residents
the last review of the prescriptions of 17.5% of the psychotropic drugs was at
least 3 months to partly years ago. Based on the American Beers-criteria 13.6% of
the consumers of psychotropic drugs received psychotropic drugs, which preferably
should not be taken by older people.
PMID- 17039289
TI - [Age differences in psychosocial resources and psychological well-being of cancer
patients at the start of chemotherapy].
AB - It has been suggested that older patients would have fewer resources than younger
patients. We assessed psychosocial resources in 361 recently diagnosed cancer
patients. Older patients had a stronger internal health-related locus of control
but also less hope than younger patients. No age differences were found for self
esteem and perceived social support. In addition, older patients reported lower
levels of negative and positive affect. Curative-intended therapy and social
support were associated with a more positive affect only in younger patients,
whereas hope was only related to older patients' psychological well-being. It is
concluded that older cancer patients have similar levels of psychosocial
resources compared to younger patients, but that lack of hope is a vulnerability
factor for older patients in particular.
PMID- 17039290
TI - [The impact of different reference groups for the assessment of quality of life
in people suffering from dementia-determination of competence groups with HILDE].
AB - The HILDE project proceeds from a theoretical conception of quality of life which
considers both the significance of objective living conditions claimed in the
Swedish level of living approach and the significance of processes of subjective
perceptions and judgements accentuated in the American quality of life approach.
Since component definitions of quality of life regularly fail to reflect
empirical relationships between the differentiated aspects, quality of life is
defined as a constellation of personal and environmental material and immaterial
resources and subjective wellbeing. Under the assumption that an adequate
assessment of quality of life of people with dementia can not exclusively be
based on their cognitive impairment, i.e. their stage of the disease, but must
also reflect the realisation of individual preferences in a given life situation,
the empirical portion of this contribution identifies and independently cross
validates in random subsamples four patterns of competence in a sample of 362
nursing home residents suffering from dementia. Each of these four different
dementia syndrome groups is characterised by specific needs and values. They can
be used as a point of reference within as well as between these competence
groups, in order to plan individual interventions with competence-oriented
expectations.
PMID- 17039291
TI - [Communication training for family caregivers of dementia patients].
AB - The program Kommunikations-TAnDem was developed with the primary purpose of
increasing the communication competence of family caregivers of dementia
patients. Further aims were to reduce the burden of family caregivers and to
increase the quality of life of dementia patients. The effectiveness of the
Kommunikations-TAnDem was tested in a controlled training study with 22
participants using a waiting-group control design and process measurement. The
results of the study verify effects for the variables "Communication competence",
"Caregivers knowledge about communication in dementia", "Quality of life of
dementia patients" and "Directly perceived burden of family caregivers. Therefore
it can be concluded that the Kommunikations-TAnDem is a method of indirectly
supporting dementia patients by training the family caregivers. The results of
research in this program underline very clearly the relevance of the inclusion of
the family caregivers in intervention programs and the importance of
communication competence for the well-being of dementia patients and their
caregivers.
PMID- 17039292
TI - [Rehabilitation processes and sustainability: first results of a rehabilitation
study of geriatric stroke patients].
AB - A rehabilitation care management oriented towards the severity of the disease,
the individual competence and the patient's needs essentially improves the
effectivity and the sustainability of inpatient rehabilitation. The Institute of
Gerontology of the University of Heidelberg is developing an assessment for
elderly stroke patients to optimize placement decision by an early rehabilitation
prognosis. Data concerning functional, cognitive and psychological status were
collected in 267 patients participating in a postacute rehabilitation program on
admission, after two weeks and on discharge and six weeks later. In this article
are presented the study design and patients' characteristics during the
rehabilitation process. The first assessment at admission gives important
information about the sustainability of the ADL-competence after discharge.
Severe stroke, premorbid ADL-competence, cognitive impairment, communication
problems, depression and higher age were found to be predictors for the outcome
of the rehabilitation process.
PMID- 17039293
TI - Advance directives: prerequisites and usefulness.
AB - Advance directives allow competent persons to extend their right of self
determination into the future, by recording choices that are intended to
influence their future care should they become unable to make choices. They are
considered tools to facilitate end-of-life decision making. Advance directives
are a form of anticipatory decision-making. This article will focus on
instruction directives against a certain treatment, so-called advance refusals.
The most important legal requirement is the acknowledgement of patient autonomy.
This condition is met in all European countries. The legal uncertainties
surrounding advance refusals are focused on practical modalities rather than on
the validity of the general principle. According to leading ethics the underlying
moral rule of advanced directives is that all truly autonomous refusals of
treatment must be respected, no matter what the consequences. Physicians find it
hard to adhere to the wishes and choices of patients as expressed in directives.
They find the text ambiguous. Another weakness is that directives give little
information about what in the patient's view constitutes a good quality of life.
Some health professionals lack the willingness to step outside their own value
systems and fully embrace that of the patient. Empathic skills are required. Very
few persons create an advance directive. Furthermore, of the created directives
only some are accessible when patients are admitted to hospital. However, when
directives are available they usually influence medical treatment decisions.
PMID- 17039294
TI - [Palliative care in nursing homes: central issues and further research].
AB - Palliative Care and the Hospice Movement meet many of the challenges nursing
homes are currently faced with. There are different approaches dependent on the
rules and culture of the national health care systems. The reviewed literature
shows that Palliative Care in Nursing Homes lacks quality, especially in the care
given to residents with dementia. Apart from that, a palliative culture in the
organizations has to be developed. In this paper, central issues and topics for
further research to improve Palliative Care in Nursing Homes are presented.
PMID- 17039295
TI - [Sexual victimization in old age].
AB - A study on the underresearched topic of elderly sexual victimization combined
multiple data sources: German police crime statistics, 122 public prosecutor
files on sexual victimization of people above age 60, survey data from 76
institutions assisting victims of sexual violence/domestic violence, in-depth
interviews with 22 practitioners who had worked with sexually victimized elderly.
The study shows that few cases of sexual victimization in old age are known to
law enforcement agencies or victim services. Offences dealt with by the criminal
justice system differ significantly from those known to battered women's shelters
and victim services. The majority of incidents prosecuted by the criminal justice
system are hands-off offences; hands-on offences are typically single incidents
committed by strangers or loose acquaintances of the victim. Battered women's
shelters and institutions of victim assistance are confronted with severe forms
of sexual violence in intimate relationships, the prototypical case being an
older woman who is repeatedly victimized by her husband over a considerable
period of time and within a relationship characterized by a comprehensive system
of violence, humiliation, and control (corresponding to Johnson's concept of
intimate terrorism). The study demonstrates how small numbers of recorded cases
of sexual violence in old age may reflect age-specific detection rates. It
provides evidence on older victims' help-seeking behavior and on ways to improve
victim services.
PMID- 17039297
TI - [Announcements of the BAG].
PMID- 17039296
TI - [Announcements of the DGGG].
PMID- 17039299
TI - Alzheimer 100--highlights in the history of Alzheimer research.
AB - Alzheimer disease, a progressive neurodegenerative disorder of hitherto unknown
etiology leading progressively to severe incapacity and death, has become the
pandemic of the 21(st) century. On World Alzheimer Day, September 21, 2006, the
100(th) anniversary of the first description of the clinical and histological
findings in this disorder by A. Alzheimer, was celebrated. This retrospective
review of the most important events and advances in Alzheimer research presents
its early history in which only clinical and histologic signs of this peculiar
disease were described. Electron microscopy, quantitative morphology and modern
biochemistry emerging in the second half of the 20(th) century opened a new era
in dementia research with description of the ultrastructure and biochemistry of
senile plaques and neurofibrillary tangles, the major disease markers of AD.
Advances in the development of clinical, neuropathological, and neuroimaging
criteria, modern instruments and algorithms in the diagnosis of the disorder
followed, enabling long-term studies and more exact diagnosis of AD and related
disorders. Landmark studies were the development of operational criteria for the
post mortem diagnosis of AD based on semiquantitative assessment and
developmental patterns of its major markers. Basic research gave insight into the
molecular genetics and pathophysiology of AD, and, based on the biochemical
findings, new pharmacological treatment options were opened. Recently, biological
and other surrogate, in particular functional neuroimaging, markers allow an
early detection of presymptomatic stages of AD, their risk factors and
progression which, in the future, might be prevented or at least slowed by new
therapeutic approaches. Since the etiology of AD is hitherto unknown, causative
therapies are still not available. The paper discusses future research needs and
challenges for developing new diagnostic strategies for early and accurate
detection of neurodegenerative processes leading to dementia, better
epidemiologic and gender data as well as more insights into the pathogenic
cascade of AD and other dementing disorders which will depend on international
networks and close cooperation between clinicians, neuroscientists, caregivers,
public health institutions, and individual sponsors.
PMID- 17039301
TI - Treatment of hydrocephalus with functionally isolated ventricles.
AB - Rapid therapeutic drainage of one lateral ventricle may lead to ipsilateral slit
ventricle, and the resultant functional obstruction of cerebrospinal fluid flow
through the foramen of Monro may cause dilatation of the contralateral ventricle.
Drainage of the lateral ventricle with a low-pressure shunt led to functionally
isolated contralateral ventriculomegaly in this report. The patient's condition
was complicated by a Candida albicans shunt infection. Following effective
treatment of the infection by chemotherapy and removal of the shunt system, the
patient was treated by bridging two lateral ventricles with ventricular catheters
connected to an Ommaya reservoir. An occipital ventricular catheter was then
inserted and connected to a programmable valve to drain the bridged lateral
ventricles. Modern centers, caring for patients with infantile hydrocephalus,
should have endoscopic facilities available but in cases with extensive
ventricular adhesions and in asymmetric hydrocephalus where endoscopic septostomy
between the ventricles is impossible our described technique may be used.
PMID- 17039300
TI - Auditory event-related potentials in subcortical vascular cognitive impairment
and in Alzheimer's disease.
AB - BACKGROUND: Few studies exist on ERPs and patients with subcortical vascular
cognitive impairment (SVCI). This latter is a quite homogeneous subtype of
vascular dementia whose cognitive profile is quite different from that of
Alzheimer disease (AD). AIMS: The present study aims at comparing the ERPs
profile both in patients with SVCI and in patients with AD. SUBJECTS AND METHODS:
ERPs and psychometric tests were collected from 39 healthy elderly controls, 51
patients with SVCI and 43 patients with AD. Subjects mentally count high pitched
target tones that were randomly intermixed with low pitched frequent tones. We
measured ERPs latencies (N1, P2, N2 and P3), and interpeak latencies (N1-P3, N1
P2, N1-N2). RESULTS: Grand averaged potentials in SVCI showed a significant
increase of P3 latency. AD patients showed a prolongation of N1, P2, N2, P3
latencies. As far as interpeak latencies are concerned, SVCI patients showed a
significant prolongation of N1-P3, AD patients had a significant increase of N1
N2, and N1-P3 intervals. When all patients were considered as a single group,
correlation of neuropsychological tests scores showed a significant negative
relationship between P300 latency and, respectively, Mini Mental Status
Examination, auditive and visual span forward. In both groups, ERPs latency
sensitivity, was low, whilst specificity values were quite high. CONCLUSIONS: Our
finding suggest that these two dementing diseases have different
electrophysiologic features that may be related to their specific underlying
pathogenetic mechanism; in particular, we hypothesise that, differently from AD,
P300 latency prolongation characterizes the early stage of SVCI. So, this ERPs
approach could be helpful to detect early alterations of the attentional/working
memory functions in patients with subcortical ischaemic vascular disease.
PMID- 17039302
TI - Injection therapy of lumbar facet syndrome: a prospective study.
AB - BACKGROUND: Chronic low back pain remains a major health problem. Facet joint
injection therapy is an easy to perform therapeutic option. However, few
prospective studies use a standardized protocol to investigate injection therapy.
The aim of our study was to evaluate quantity and duration of clinical
improvement after this protocol, and to identify the best time for additional
repetitive injection therapy. MATERIALS AND METHODS: Thirty-nine patients (21
men, 18 women; mean age 55.2 years [range, 29-87 years]) with lumbar facet
syndrome were treated with injection using a standardized protocol (prednisolone
acetate, lidocaine 1%, phenol 5%) under fluoroscopic control. Follow-up was based
on a specially designed questionnaire. Analysis included MacNab criteria, visual
analogue scale, and pain disability index. RESULTS: Reduction of pain was found
up to 6 months after treatment. The outcome was assessed excellent or good by 62%
(24 patients) of the patients after 1 month, by 41% (16 patients) after 3 months,
and by 36% (14 patients) after 6 months. There was no influence of age, body mass
index, or previous lumbar spinal surgery on improvement after treatment. There
were no severe side effects. Short-lasting self limiting mild side effects were
found in 26% (increased back pain, numbness, heartburn, headache, allergy).
CONCLUSION: Facet joint injection therapy using a standardized protocol is safe,
effective, and easy to perform. The clinical effect is limited, and we recommend
repetitive injection according to this protocol after 3 months.
PMID- 17039303
TI - Intracranial pulse pressure amplitude levels determined during preoperative
assessment of subjects with possible idiopathic normal pressure hydrocephalus.
AB - BACKGROUND: It was previously reported that the intracranial pulse pressure
amplitudes were elevated in idiopathic normal pressure hydrocephalus (iNPH)
patients responding to shunt surgery. In this study, pulse pressure amplitudes
were determined in all patients referred for tentative iNPH, and patients were
selected for shunt surgery based on the determination of their threshold levels
of intracranial pulse pressure amplitudes. PATIENTS AND METHODS: All patients
referred to our department for tentative iNPH during a 12 months time period were
included. Using intracranial pressure (ICP) monitoring the intracranial pulse
pressure amplitudes were determined as the mean wave amplitude in consecutive 6
seconds time windows. Intracranial pulse pressure amplitudes were defined as
being elevated when the mean wave amplitudes were either >or=4 mmHg in >or=70%,
>or=5 mmHg in >or=40% or >or=6 mmHg in >or=10% of the ICP recording time. Shunt
treatment was offered to those with elevated mean wave amplitudes. Clinical state
was assessed by using a NPH Grading Scale and the Stein-Langfitt scale before ICP
monitoring, and then repeated after 12 months. RESULTS: Among the 40 iNPH
patients included during the 12 months period, the mean wave amplitudes were
elevated in 24 patients (60%), while not being elevated in 16 (40%). Neither pre
operative clinical state, radiological ventricular size nor co-morbidity differed
between patient groups with elevated or non-elevated mean wave amplitudes. In the
shunted patients who had pre-operatively elevated mean wave amplitudes, 91% had
very significant clinical change after 12 months (median change in NPH score +4).
In those with non-elevated amplitudes and no shunt, clinical state was somewhat
worse after 12 months (median change in NPH score -1). CONCLUSIONS: In this one
year material, mean wave amplitudes were elevated in 60% of iNPH patients. In
those with elevated mean wave amplitudes who were treated with shunt, 91% had a
significant clinical response.
PMID- 17039304
TI - Intrasellar paraganglioma: a case report and review of the literature.
AB - Intrasellar paragangliomas are very rare lesions with only six previous cases
described in the literature. We present a further case of intrasellar
paraganglioma. The patient was a 52 yr-old man who developed two transient
ischemic attacks. A CT scan showed an intra- and supra-sellar expanding lesion,
which was regarded as a possible non-functioning pituitary macro-adenoma. Removal
of the lesion was accomplished by transsphenoidal surgery. Histological
examination was diagnostic of a paraganglioma. We review the literature and
discuss pathological features and possible pathogenesis of sellar and parasellar
paragangliomas, underlining the necessity to consider paraganglioma in the
differential diagnosis of sellar lesions.
PMID- 17039305
TI - Primary germinoma arising from the midbrain.
AB - A 29-year-old man presented with diplopia, dysarthria, anisocoria, oculomotor
nerve paralysis, abducens nerve paralysis, right facial palsy, and spastic
hemiparetic gait. Magnetic resonance imaging (MRI) showed a homogenously enhanced
mass in the midbrain. MRI-guided stereotactic biopsy was performed, and the
histologic diagnosis was pure germinoma. The tumor disappeared after chemotherapy
and radiotherapy. Germinoma should be included in the differential diagnosis of
midbrain lesions in young adults. MRI-guided stereotactic biopsy provided a
helpful diagnostic clue in a patient with a midbrain lesion.
PMID- 17039298
TI - The significance of the cholinergic system in the brain during aging and in
Alzheimer's disease.
AB - Acetylcholine is widely distributed in the nervous system and has been implicated
to play a critical role in cerebral cortical development, cortical activity,
controlling cerebral blood flow and sleep-wake cycle as well as in modulating
cognitive performances and learning and memory processes. Cholinergic neurons of
the basal forebrain complex have been described to undergo moderate degenerative
changes during aging, resulting in cholinergic hypofunction that has been related
to the progressing memory deficits with aging. Basal forebrain cholinergic cell
loss is also a consistent feature of Alzheimer's disease, which has been
suggested to cause, at least partly, the cognitive deficits observed, and has led
to the formulation of the cholinergic hypotheses of geriatric memory dysfunction.
Impaired cortical cholinergic neurotransmission may also contribute to beta
amyloid plaque pathology and increase phosphorylation of tau protein the main
component of neurofibrillar tangles in Alzheimer's disease. Understanding the
molecular mechanisms underlying the interrelationship between cortical
cholinergic dysfunction, beta-amyloid formation and deposition, and tau pathology
in Alzheimer's disease, would allow to derive potential treatment strategies to
pharmacologically intervene in the disease-causing signaling cascade.
PMID- 17039306
TI - Application of cellular gene therapy for rheumatoid arthritis.
AB - Rheumatoid arthritis (RA) is a common autoimmune disease characterized by
persistent inflammation of joints resulting in progressive destruction of
cartilage and bone. Recently, biological agents that suppress the activities of
proinflammatory cytokines have shown efficacy as antirheumatic drugs, but require
frequent administration, and often result in systemic immune suppression. Thus,
gene transfer approaches are being developed as an alternative approach for
targeted, more efficient, and sustained delivery of inhibitors of inflammatory
cytokines as well as other therapeutic agents. Several gene therapy approaches
have been established in preclinical animal models. In these models, autoantigen
specific T cells have been demonstrated to be ideal gene delivery vehicles for
the local delivery of "immunoregulatory molecules" because these cells have
tissue-specific homing and retention properties. Indeed, bioluminescence studies
in an animal model of inflammatory arthritis revealed that these cells
accumulated in and remained in inflamed joints. Transfer of genetically modified
dendritic cells (DCs) may also have interesting effects. We conclude that
modifying antigen-specific T cells or autologous DCs by retroviral transduction
for local expression of regulatory proteins is a promising therapeutic strategy
for the treatment of RA.
PMID- 17039307
TI - Autoimmunity to citrullinated type II collagen in rheumatoid arthritis.
AB - The production of autoantibodies to citrullinated type II collagen and the
citrullination of type II collagen were analyzed in rheumatoid arthritis.
Autoantibodies to citrullinated type II collagen were detected in 78.5% of serum
samples from 130 rheumatoid arthritis patients. Autoantibodies to native
noncitrullinated type II collagen were detected in 14.6% of serum samples, all of
which were positive for anti-citrullinated type II collagen antibodies. Serum
samples were also positive for anti-citrullinated type II collagen antibodies in
1 of 31 systemic lupus erythematosus patients and 2 of 55 patients with
osteoarthritis of the knee. In contrast, sera samples from 24 systemic sclerosis
patients, 21 dermatomyositis/polymyositis patients, 21 ankylosing spondylitis
patients, and 18 psoriatic arthritis patients were all negative for anti
citrullinated type II collagen antibodies. Anti-citrullinated type II collagen
antibodies and fragments of citrullinated type II collagen were found in the
synovial fluid obtained from affected knee joints of 15 rheumatoid arthritis
patients. Moreover, anti-citrullinated type II collagen antibodies were isolated
from the synovium of affected knee joints in 8 rheumatoid arthritis patients
using antigen/antibody immunocomplex dissociation buffer but not by using
standard buffers. These findings indicate that autoantibodies that react with
citrullinated type II collagen are specifically produced and that immunocomplexes
composed of fragments of citrullinated type II collagen and autoantibodies are
deposited in the inflamed articular synovium in rheumatoid arthritis patients.
Assaying for the presence of anti-citrullinated type II collagen antibodies may
therefore be useful for diagnosing rheumatoid arthritis, and the deposition of
these immunocomplexes in the articular synovium may be involved in pathogenesis.
PMID- 17039308
TI - Evaluation of Pneumocystis pneumonia infection risk factors in patients with
connective tissue disease.
AB - We conducted a retrospective, clinical evaluation of connective tissue disease
(CTD) patients who were tested for either sputum or bronchoalveolar lavage fluid
Pneumocystis polymerase chain reaction (PC-PCR) and analyzed the risk factors
that cause Pneumocystis pneumonia (PCP) susceptibility and fatality. PC-PCR was
performed on 66 CTD patients who presented with symptoms, data, or radiological
findings strongly suggesting respiratory infection. Patients with higher oral
corticosteroid doses, use of oral methotrexate (MTX), bilateral lung findings,
positive beta-D-glucan, and no prophylaxis use were more susceptible to PCP. They
had significantly low immunoglobulin G and significantly high beta-D-glucan and
lactate dehydrogenase. Survivors and nonsurvivors of PCP were also evaluated.
Poor prognoses were observed with older age, elevated beta-D-glucan, rheumatoid
arthritis (RA) patients using MTX, hypoxemia, bilateral lung findings, and
mechanical ventilation use. Nonsurvivors had significantly lower lymphocytes,
oxygen saturation, and significantly higher beta-D-glucan. In RA, poor prognoses
were seen with those taking MTX. Disease duration, underlying pulmonary
complications, and oral corticosteroid doses did not lead to poor prognoses in
RA. Because PCP in CTD leads to abrupt onset of symptoms with poor survival
rates, early diagnosis and initiation of treatment are critical, and it is
essential for clinicians to recognize risk factors that predispose patients to
PCP and its mortality.
PMID- 17039309
TI - A biomechanical study of activities of daily living using neck and upper limbs
with an optical three-dimensional motion analysis system.
AB - In activities of daily living such as eating meals, the neck and upper limbs move
in coordination. However, no methods have been established to analytically and
quantitatively capture motion of the neck and limbs during these activities. We
used a Vicon 512 system to simultaneously measure ranges of motion (ROMs) for the
cervical spine, shoulders, elbows, and forearms. Correlations between the motion
analyzer and the universal goniometer were >0.76. Repeatability of measurements
using this analyzer were or = 75 years old. The ongoing increase
of life expectancy to 75.6 years in men and 81.3 years in women was associated
with a remarkable decrease of cardiovascular and ischemic heart disease (IHD)
mortality and an increasing disease-specific mean age of death. Each third male
and each fourth female death from IHD could be prevented, whereas the absolute
number of nonfatal acute myocardial infarction (AMI) increased in the younger
ages and decreased in the higher age groups. Since 1985, the total number of
fatal and nonfatal cases of AMI has decreased by 24% in men and by 22% in women;
two thirds of male and one third of female cases occur before the 75th year of
age. These positive trends are mainly the result of a more effective acute and
long-term therapy after AMI onset. Actually, 35% of all AMI patients do not
survive the first day after acute onset and in up to 90% of them classic risk
factors (hypertension, dyslipidemia, diabetes, cigarette smoking) were present.
Therefore, the theme number 1 for the population must be intensified activities
of primary prevention.
PMID- 17039325
TI - [Interdisciplinary guidelines for diagnosis and therapy of extracerebral
amyloidosis: issued by the German Society of Amyloid Diseases e. V.
(www.amyloid.de)].
PMID- 17039326
TI - [Chronic interstitial nephritis in an 18-year-old due to intake of a compound
analgesic].
AB - BACKGROUND: Renal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs)
are acute renal failure due to an impaired perfusion caused by inhibition of
prostaglandin synthesis, acute allergic interstitial nephritis as well as acute
toxic tubular necrosis. Moreover, chronic renal failure may occur due to a
chronic interstitial nephritis or an analgesic nephropathy that is characterized
by capillary sclerosis and papillary necrosis in addition to chronic interstitial
nephritis. In contrast to acute renal insufficiency that may already occur after
a single NSAID dose, analgesic nephropathy is a disease caused by long-term
intake of NSAID compound analgesics and predominantly affects the middle and old
age. CASE REPORT: An 18-year-old patient with a 4-year history of NSAID compound
analgesic intake presented to the urology department with right-sided flank pain
and increased serum creatinine. An obstruction as well as nephrolithiasis were
ruled out and the patient was referred to the medical department. Urinalysis
showed leukocyturia, mild microhematuria as well as proteinuria of 2.2 g/day
whereupon a diagnostic kidney biopsy was performed. Histology revealed a chronic
nonpurulent destructive interstitial nephritis. After cessation of analgesic
intake, the serum creatinine level fell to the normal range; however, a reduced
creatinine clearance persisted indicating chronic renal damage. CONCLUSION: The
present case is remarkable in that chronic renal damage due to intake of a
compound analgesic was already observed in an 18-year-old patient. In this
context, the permission of NSAID compound analgesics and their free over-the
counter sale to adolescents need to be critically questioned.
PMID- 17039327
TI - [Cytomegalovirus-induced colitis in an immunocompetent old patient].
AB - BACKGROUND: The cytomegalovirus (CMV) causes multiple diseases in patients with
immunodeficiency. Also in patients with chronic inflammatory bowel disease,
superinfections with CMV are known. Reactivation or infection is possible in rare
cases in immunocompetent patients. CMV-induced colitis should be considered a
differential diagnosis especially in patients suffering from diarrhea or bloody
stools. CASE REPORT: The case of an 87-year-old patient with severe colitis is
reported, who did not suffer from chronic inflammatory bowel disease nor from
immunodeficiency. The most important hint came from the pathologist. The clinical
outcome under antiviral therapy with ganciclovir was good. CONCLUSION: Even in
immunocompetent patients, CMV-induced colitis should be taken into consideration,
especially in elderly people.
PMID- 17039328
TI - [The German program for disease management guidelines. Background, methods, and
development process].
AB - The Program for National Disease Management Guidelines (German DM-CPG Program)
was established in 2002 by the German Medical Association (umbrella organization
of the German Chambers of Physicians) and joined by the Association of the
Scientific Medical Societies (AWMF; umbrella organization of more than 150
professional societies) and by the National Association of Statutory Health
Insurance Physicians (NASHIP) in 2003. The program provides a conceptual basis
for disease management, focusing on high-priority health-care topics and aiming
at the implementation of best practice recommendations for prevention, acute
care, rehabilitation and chronic care. It is organized by the German Agency for
Quality in Medicine, a founding member of the Guidelines International Network (G
I-N). The main objective of the German DM-CPG Program is to establish consensus
of the medical professions on evidence-based key recommendations covering all
sectors of health-care provision and facilitating the coordination of care for
the individual patient through time and across interfaces. Within the last year,
DM-CPGs have been published for asthma, chronic obstructive pulmonary disease,
type 2 diabetes, and coronary heart disease. In addition, experts from national
patient self-help groups have been developing patient guidance based upon the
recommendations for health-care providers. The article describes background,
methods, and tools of the DM-CPG Program, and is the first of a publication
series dealing with innovative recommendations and aspects of the program.
PMID- 17039329
TI - [DRG and coding: alcoholism and withdrawal].
PMID- 17039330
TI - Drug-induced granulomatous interstitial nephritis in a pediatric patient.
AB - Acute interstitial nephritis (AIN) is a known cause of acute renal failure in
children. In most instances, drug therapy is the offending agent. Although
granuloma formation has been observed in drug-induced interstitial nephritis, it
is not a commonly associated manifestation. This is a case of a 15-year-old white
female with Tetralogy of Fallot and pulmonary atresia who developed acute renal
failure secondary to drug-induced interstitial nephritis and renal granulomas. In
addition to interstitial edema with eosinophils and lymphocytes, her renal biopsy
showed interstitial granulomas, immune complexes within tubular basement
membranes, and the unusual feature of multinucleated giant cells engulfing
tubules. Her acute renal failure resolved after the withdrawal of antibiotics and
the initiation of intravenous steroid therapy.
PMID- 17039331
TI - A confused child. Diagnosis: urinary tract infection, dilated urinary system and
associated hyperammonaemic encephalopathy.
PMID- 17039332
TI - Acute renal failure from xanthine nephropathy during management of acute
leukemia.
AB - Tumor lysis syndrome is a potentially life-threatening complication of induction
chemotherapy for treatment of lymphoproliferative malignancies. Serious
complications of tumor lysis syndrome are rare with the preemptive use of
allopurinol, rasburicase, and urine alkalinization. We report a case of oliguric
acute renal failure due to bilateral xanthine nephropathy in an 11-year-old girl
as a complication of tumor lysis syndrome during the treatment of T-cell acute
lymphoblastic leukemia. Xanthine nephrolithiasis results from the inhibition of
uric acid synthesis via allopurinol which increases plasma and urinary xanthine
and hypoxanthine levels. Reports of xanthine nephrolithiasis as a cause of tumor
lysis syndrome are rare in the absence of defects in the hypoxanthine-guanine
phosphoribosyl transferase (HGPRT) enzyme. Xanthine nephropathy should be
considered in patients who develop acute renal failure following aggressive
chemotherapy with appropriate tumor lysis syndrome prophylaxis. Urine
measurements for xanthine could aid in the diagnosis of patients with
nephrolithiasis complicating tumor lysis syndrome. Allopurinal dosage should be
reduced or discontinued if xanthine nephropathy is suspected.
PMID- 17039333
TI - Does citrate prevent nephrocalcinosis in preterm neonates?
AB - Nephrocalcinosis (NC) occurs frequently in preterm neonates. A high U
calcium/citrate is one of the contributing factors to the development of NC. In
stone-forming children and adults citrate supplementation is a successful
preventive therapy. In this randomized controlled trial the effect of citrate
therapy was studied on the development of NC in preterm neonates with a
gestational age <32 weeks. Thirty-eight preterm neonates (mean gestational age
29.8 weeks (SD 1.6), mean birth weight 1,300 g (SD 351) were treated with sodium
citrate (0.52 mmol/kg/day in four doses) from day 8 of life until at term and 36
preterm neonates (mean gestational age 29.6 weeks (SD 1.6), mean birth weight
1,282 g (SD 256) were not treated. U-calcium, U-creatinine, U-citrate and U-pH
were measured at day 7, 14, 21, 28 of life and at term. Renal ultrasonography
(US) was performed at term. U-citrate/creatinine and U-pH were significantly
higher and U-calcium/citrate was significantly lower in the citrate group at day
14, 21 and 28 compared with the control group (P<0.05). Complications of citrate
administration were not encountered, however the incidence of NC was not
significantly different in the treated (34%) compared with the control group
(44%), P=0.37. Preterm neonates treated with citrate in the first months of life
have higher U-citrate/creatinine and lower U-calcium/citrate compared with
controls. Sodium citrate therapy in a dosage of 0.52 mmol/kg/day is safe but does
not prevent NC. Whether a higher dose or potassium citrate decreases the
incidence of NC should be evaluated in further studies.
PMID- 17039334
TI - The effect of aldosterone blockade in patients with Alport syndrome.
AB - Recent studies indicate that adding the mineralocorticoid receptor antagonist
spironolactone (SP) to angiotensin converting enzyme inhibitors (ACEI) or ACEI
and angiotensin receptor blocker (ARB), which is known as a triple blockade,
enhances the more beneficial effects on urinary protein excretion of patients
with chronic kidney diseases. In this study, we explored the effects of SP on
urinary protein excretion in patients with Alport syndrome featuring persistent
proteinuria in spite of the long-term use of ACEI (lisinopril) or both ACEI and
ARB (candesartan). Five patients with Alport syndrome were enrolled and SP
treatment (25 mg/day) was started. At the start of SP administration, all
patients showed good renal function and none of them suffered from hypertension.
We decided to assess the effect of SP by determining the morning urinary
protein/creatinine ratio (U-P/C) and estimated glomerular filtration rate (EGFR).
After SP treatment was started, U-P/C was significantly reduced at 3, 6, 12 and
18 months, while EGFR did not change. The drop in systolic and diastolic blood
pressure was statistically significant and serum potassium level was slightly
elevated. None of the patients showed signs of severe hyperkalemia (>5.0 mEq/l).
These results suggest that aldosterone receptor blockade combined with ACEI and
ARB therapy offers a valuable adjuvant treatment for the reduction of proteinuria
in patients with Alport syndrome as in those with other chronic kidney diseases.
SP can thus be expected to constitute a good renoprotective agent for Alport
syndrome. These preliminary data indicate that large-scale trials of this therapy
should be done.
PMID- 17039335
TI - [Introduction to the topic: blood really is a very special fluid!].
PMID- 17039337
TI - [Anxiety and depression after loss of a lower limb].
AB - A good number of psychosocial-, disease-, and disability-related variables
influence the adaptation process after the loss of a lower limb. In this case
psychological problems, as a result of a failed adaptation process, are common.
Of the 75 patients examined who had an amputation of a lower extremity 27% showed
increased depression and 25% increased anxiety scores; 18.3% showed higher than
normal scores in both categories. Regression analysis showed that in addition to
pain reception poor acceptance of the prosthesis is an important predictive
factor for the development of psychological disorders and diseases like anxiety
and depression. Therefore, measures for psychological diagnostics and care should
be initiated soon after the amputation to prevent psychological abnormalities.
Here interdisciplinary management and cooperation of the professions involved in
the care of the patient are recommended.
PMID- 17039336
TI - [Insoles for the rheumatic foot. A clinical and pedobarographic analysis].
AB - BACKGROUND: Insoles are regarded as an appropriate tool for the management of
rheumatic foot disorders. However, a quality control for this purpose has not
been established. In our study, the clinical effectiveness of insoles used in
patients with rheumatic foot disorders was addressed. In addition, we sought to
establish pedobarography as a means of quality control for orthotic management of
the rheumatic foot. MATERIAL AND METHODS: Our study included 20 rheumatoid
arthritis patients with painful rheumatic foot deformities who were provided with
insoles. Clinical data were obtained by physical examination and a 100-mm pain
scale. Pedobarography was performed using the novel pedar cable system with new
and individually designed insoles and after a 6-month follow-up. A shoe-only
trial served as control. The parameters maximum force, peak pressure, force-time
integral, and average pressure were analyzed in anatomical regions and an
individually defined overloaded forefoot region. RESULTS: Clinical improvement
was significant after a 6-month follow-up in spite of a heterogeneous group of
patients. However, our results could not confirm consistent changes in plantar
pressure distribution. CONCLUSION: As a conclusion, further efforts are necessary
to establish a quality control for orthotic management of the rheumatic foot.
PMID- 17039338
TI - [Labial salivary gland biopsy in Sjogren's syndrome].
AB - In the majority of cases, autoimmune sialadenitis is a feature of Sjogren's
syndrome. This systemic autoimmune disease is, therefore, clinically
characterised by sicca symptoms such as xerostomia and keratoconjunctivitis
sicca. Since autoimmune sialadenitis affects major as well as minor salivary
glands, histopathological examination is almost always carried out using labial
salivary gland biopsies. A positive histopathological result is determined as a
focal lymphocytic sialadenitis with at least one aggregate of 50 or more
lymphocytes and histiocytes per 4 mm2 of salivary gland tissue. As one out of
four objective findings, focus scoring belongs to the classification criteria for
Sjogren's syndrome according to the American-European consensus group.
PMID- 17039339
TI - Acute fracture of the os trigonum.
AB - A 21-year-old man presented with ankle pain after a motor vehicle accident.
Imaging revealed an acute fracture of the os trigonum in addition to multiple,
other lower-extremity fractures. In this case, the fracture of the os trigonum
was a result of a significant traumatic injury. Thus, the presence of this
fracture in an acute setting should prompt a search for other associated
fractures.
PMID- 17039340
TI - Massive hemoperitoneum due to ruptured inferior phrenic artery pseudoaneurysm
after blunt trauma.
AB - There had been no previous reports of ruptured pseudoaneurysm of inferior phrenic
artery shortly after blunt abdominal trauma. Traumatic arterial pseudoaneurysms
are either iatrogenic or the result of penetrating injuries and one of the
sequelae of trauma. Post-traumatic pseudoaneurysm develops at varying time
intervals after the initial insult. To our knowledge, this is the first report of
massive hemoperitoneum caused by ruptured inferior phrenic artery pseudoaneurysm
after blunt trauma. Pseudoaneurysm of inferior phrenic artery in patient with
diaphragm injury is potentially a life-threatening condition and requires urgent
management. Diagnosis of ruptured inferior phrenic artery pseudoaneurysm is based
on clinical assessment combined with radiological investigations. We report a
case of ruptured left inferior phrenic artery pseudoaneurysm as one aspect of
massive hemoperitoneum caused by blunt abdominal trauma.
PMID- 17039341
TI - Case report: urinary retention secondary to a foreign body in the male urethra.
AB - We report the case of a male patient who presented to the Emergency Department
with urinary retention secondary to a suspected foreign object in his urethra. We
review the diagnosis and management of self-inserted urethral foreign objects in
men. Emergent treatment is necessary in patients with urethral foreign objects.
Prompt radiologic studies should be obtained because immediate bladder access and
drainage is mandatory, especially in patients presenting with urosepsis or
urinary retention. Endoscopic removal is the management of choice.
PMID- 17039342
TI - A novel multiple-trauma CT-scanning protocol using patient repositioning.
AB - Emergency CT examination is considered to be a trade-off between a short scan
time and the acceptance of artifacts. This study evaluates the influence of
patient repositioning on artifacts and scan time. Eighty-three consecutive
multiple-trauma patients were included in this prospective study. Patients were
examined without repositioning (group 1, n=39) or with patient rotation to feet
first with arms raised for scanning the chest and abdomen/pelvis (group 2, n=44).
The mean scan time was 21 min in group 1 and 25 min in group 2 (P=0.01). The mean
repositioning time in group 2 was 8 min. Significantly, more artifacts were
observed in group 1 (with a repeated scan in 7%) than in group 2 (P=0.0001). This
novel multiple- trauma CT-scanning protocol with patient repositioning achieves a
higher image quality with significantly fewer artifacts than without
repositioning but increases scan time slightly.
PMID- 17039343
TI - Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.
AB - Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in
single-layered epithelia of the gastrointestinal tract. Transgenic mice over
expressing human KRT8 display pancreatic mononuclear infiltration, interstitial
fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic
insufficiency. These experimental data are in accordance with a recent report
describing an association between KRT8 variations and chronic pancreatitis. This
prompted us to investigate KRT8 polymorphisms in patients with pancreatic
disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of
patients with acute and chronic pancreatitis of various aetiologies or pancreatic
cancer originating from Austria (n=16), the Czech Republic (n=90), Germany
(n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands
(n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied
4,234 control subjects from these countries and 1,492 control subjects
originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms
were analysed by melting curve analysis with fluorescence resonance energy
transfer probes. The frequency of G62C did not differ between patients with acute
or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The
frequency of G62C varied in European populations from 0.4 to 3.8%, showing a
northwest to southeast decline. The Y54H alteration was not detected in any of
the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control
subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects
of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do
not predispose patients to the development of pancreatitis or pancreatic cancer.
PMID- 17039345
TI - Aromatized arborane/fernane hydrocarbons as biomarkers for cordaites.
AB - Previous palaeobotanical and palynological studies on coals from Euramerican
Pennsylvanian ( identical with Late Carboniferous) coal basins indicate a major
change in coal-swamp floras, especially at the Westphalian-Stephanian (
approximately Kasimovian-Gzhelian, according to Geological Time Scale 2004)
boundary. A flora dominated by arborescent lycophytes was replaced by a
vegetation dominated by marattialean tree ferns in various Euramerican coal
basins. Earlier combined palynological and organic geochemical studies on
Westphalian/Stephanian coals and shales from the Saar-Nahe Basin (Germany)
revealed that the distribution of aromatized arborane/fernane hydrocarbons in
solvent extracts reflects the increasing importance of seed plants, especially
cordaites (extinct group of gymnosperms), conifers and pteridosperms. However,
the biological source of the precursor molecules could not be specified. To
clarify if the arborane/fernane derivatives MATH, MAPH, DAPH 1, and DAPH 2 in
Westphalian/Stephanian coals can be assigned to one of the three potential source
plant groups, we analyzed coals, sediments and fossil plant remains from
different Euramerican locations with respect to their biomarker composition and
stable carbon isotopic composition. Thereby, stable carbon isotopic ratios showed
only insignificant variations between Westphalian and Stephanian samples and
proved to be an unsuitable tool to describe floral changes during the
Westphalian/Stephanian of the Saar-Nahe Basin. In contrast, we were able to show
for the first time that MATH, MAPH, DAPH 1 and DAPH 2 are prominent constituents
only in extracts of cordaitean macrofossils and can therefore be regarded as
biomarkers for this group of gymnosperms.
PMID- 17039344
TI - Cold-loving microbes, plants, and animals--fundamental and applied aspects.
AB - Microorganisms, plants, and animals have successfully colonized cold
environments, which represent the majority of the biosphere on Earth. They have
evolved special mechanisms to overcome the life-endangering influence of low
temperature and to survive freezing. Cold adaptation includes a complex range of
structural and functional adaptations at the level of all cellular constituents,
such as membranes, proteins, metabolic activity, and mechanisms to avoid the
destructive effect of intracellular ice formation. These strategies offer
multiple biotechnological applications of cold-adapted organisms and/or their
products in various fields. In this review, we describe the mechanisms of
microorganisms, plants, and animals to cope with the cold and the resulting
biotechnological perspectives.
PMID- 17039346
TI - Fine mapping of the clubroot resistance gene, Crr3, in Brassica rapa.
AB - A linkage map of Chinese cabbage (Brassica rapa) was constructed to localize the
clubroot resistance (CR) gene, Crr3. Quantitative trait loci analysis using an
F(3) population revealed a sharp peak in the logarithm of odds score around the
sequence-tagged site (STS) marker, OPC11-2S. Therefore, this region contained
Crr3. Nucleotide sequences of OPC11-2S and its proximal markers showed homology
to sequences in the top arm of Arabidopsis chromosome 3, suggesting a synteny
between the two species. For fine mapping of Crr3, a number of STS markers were
developed based on genomic information from Arabidopsis. We obtained
polymorphisms in 23 Arabidopsis-derived STS markers, 11 of which were closely
linked to Crr3. The precise position of Crr3 was determined using a population of
888 F(2) plants. Eighty plants showing recombination around Crr3 locus were
selected and used for the mapping. A fine map of 4.74 cM was obtained, in which
two markers (BrSTS-41 and BrSTS-44) and three markers (OPC11-2S, BrSTS-54 and
BrSTS-61) were cosegregated. Marker genotypes of the 21 selected F(2) families
and CR tests of their progenies strongly suggested that the Crr3 gene is located
in a 0.35 cM segment between the two markers, BrSTS-33 and BrSTS-78.
PMID- 17039347
TI - Vascular depression in older people with diabetes.
AB - AIMS/HYPOTHESIS: Cerebrovascular disease may be causal or a vulnerability factor
in late-onset depression and may explain the high rate of depression in older
adults with diabetes. We explored a wide range of potential explanatory variables
of depression in a longitudinal study of older diabetic subjects to investigate
the vascular depression hypothesis in these patients. METHODS: We recruited 207
subjects with diabetes selected for potential cognitive deficits from an existing
observational cohort study (average age 75.7 +/- 4.6 years, 52.2% men) for an
assessment of depression using a standardised diagnostic instrument (Cambridge
Examination for Mental Disorders of the Elderly -- Revised). All subjects
underwent a detailed clinical assessment at baseline and at follow-up (after 7.5
+/- 1.1 years). RESULTS: Major depression was present in 45 subjects (21.7%) and
minor depression in ten (4.8%). A positive history of strokes and the presence of
peripheral arterial disease were significantly associated with depression at the
time of diagnosis. In a subsample of 93 cases who underwent structural
neuroimaging, the presence of cerebral infarcts was also significantly associated
with depression. Treatment with glucose-lowering therapy, higher serum
cholesterol levels and difficulties with activities of daily living at baseline
were significant predictors of depression at follow-up.
CONCLUSIONS/INTERPRETATION: A history of cerebrovascular disease was strongly
associated with depression and cerebrovascular risk factors were significant
predictors of depression in older diabetic patients. Our findings are consistent
with the hypothesis that the excess risk of depression in older diabetic patients
is related to underlying cerebrovascular disease.
PMID- 17039348
TI - Noninvasive assessment of cardiac output using thoracic electrical bioimpedance
in hemodynamically stable and unstable patients after cardiac surgery: a
comparison with pulmonary artery thermodilution.
AB - OBJECTIVE: To compare noninvasive cardiac output (CO)measurement obtained with a
new thoracic electrical bioimpedance (TEB) device, using a proprietary
modification of the impedance equation, with invasive measurement obtained via
pulmonary artery thermodilution. DESIGN: Prospective, observational study.
SETTING: Surgical intensive care unit (ICU) of a university-affiliated community
hospital. PATIENTS AND PARTICIPANTS: Seventy-four adult patients undergoing
elective cardiac surgery with routine pulmonary artery catheter placement.
INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Simultaneous paired CO and cardiac
index (CI) measurements by TEB and thermodilution were obtained in mechanically
ventilated patients upon admission to the ICU. For analysis of CI data the
patients were subdivided into a hemodynamically stable group and a
hemodynamically unstable group. The groups were analyzed using linear regression
and tests of bias and precision. We found a significant correlation between
thermodilution and TEB (r = 0.83; n < 0.001), accompanied by a bias of -0.01
l/min/m(2) and a precision of +/-0.57 l/min/m(2) for all CI data pairs.
Correlation, bias, and precision were not influenced by stratification of the
data. The correlation coefficient, bias, and precision for CI were 0.86 (n<
0.001), 0.03 l/min/m(2), and +/-0.47 l/min/m(2) in hemodynamically stable
patients and 0.79 (n< 0.001), 0.06 l/min/m(2), and +/-0.68 l/min/m(2) in
hemodynamically unstable patients. CONCLUSIONS: Our results demonstrate a close
correlation and clinically acceptable agreement and precision between CO
measurements obtained with impedance cardiography using a new algorithm to
calculate CO from variations in TEB, and those obtained with the clinical
standard of care, pulmonary artery thermodilution, in hemodynamically stable and
unstable patients after cardiac surgery.
PMID- 17039350
TI - Comment on "antibacterial-coated tracheal tubes cleaned with a Mucus Shaver" by
Berra et al.
PMID- 17039351
TI - Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator
associated pneumonia.
AB - OBJECTIVE: We conducted a prospective, open-label study to determine the steady
state serum and epithelial lining fluid (ELF) concentrations of unbound ertapenem
administered once daily to critically ill patients with early-onset ventilator
associated pneumonia (VAP). DESIGN AND SETTING: Prospective, open-label study in
an intensive care unit and research ward in a university hospital. PATIENTS:
Fifteen patients with VAP received 1-h intravenous infusions of 1 g ertapenem
once daily. INTERVENTIONS: After 2 days of therapy the steady-state serum and ELF
concentrations of free ertapenem were determined by high-performance liquid
chromatography. MEASUREMENTS AND RESULTS: The median (interquartile range) free
ertapenem peak (C(max)), intermediate (C(12)), and trough (C(min)) concentrations
(mg/l) 1, 12, and 24 h after the end of infusion were 30.3 (27.1-37.8), 4.8 (3.9
6.4), and 0.8 (0.5-1.2) in serum and 9.4 (8.0-10.7), 2.0 (1.1-2.5), and 0.3 (0.2
0.4) in ELF, respectively, showing a median free ertapenem percentage penetration
in ELF of approx. 30%. The median (interquartile range) serum area under
concentration-time curve of free ertapenem during the observational period was
226.7 mg h(-1) l(-1) (202.2-263.9). CONCLUSION: Our study shows satisfactory
results, with unbound ertapenem concentrations both in serum and ELF exceeding
the MIC(90) values of most of the causative pathogens encountered in early-onset
VAP during 50-100% time. This suggests that 1 g intravenous ertapenem
administered once daily should be effective during the treatment of early-onset
VAP in critically ill patients with no known risk factors for multidrug-resistant
pathogens.
PMID- 17039353
TI - Comment on "the Lund Concept for the treatment of severe head trauma
physiological principles and clinical application".
PMID- 17039354
TI - Non-invasive ventilation in chronic obstructive pulmonary disease patients:
helmet versus facial mask.
AB - RATIONALE: The helmet is a new interface with the potential of increasing the
success rate of non-invasive ventilation by improving tolerance. OBJECTIVES: To
perform a physiological comparison between the helmet and the conventional facial
mask in delivering non-invasive ventilation in hypercapnic patients with chronic
obstructive pulmonary disease. METHODS: Prospective, controlled, randomized study
with cross-over design. In 10 patients we evaluated gas exchange, inspiratory
effort, patient-ventilator synchrony and patient tolerance after 30 min of non
invasive ventilation delivered either by helmet or facial mask; both trials were
preceded by periods of spontaneous unassisted breathing. MEASUREMENTS: Arterial
blood gases, inspiratory effort, duration of diaphragm contraction and ventilator
assistance, effort-to-support delays (at the beginning and at the end of
inspiration), number of ineffective efforts, and patient comfort. MAIN RESULTS:
Non-invasive ventilation improved gas exchange (p<0.05) and inspiratory effort
(p<0.01) with both interfaces. The helmet, however, was less efficient than the
mask in reducing inspiratory effort (p<0.05) and worsened the patient-ventilator
synchrony, as indicated by the longer delays to trigger on (p<0.05) and cycle off
(p<0.05) the mechanical assistance and by the number of ineffective efforts
(p<0.005). Patient comfort was no different with the two interfaces. CONCLUSIONS:
Helmet and facial mask were equally tolerated and both were effective in
ameliorating gas exchange and decreasing inspiratory effort. The helmet, however,
was less efficient in decreasing inspiratory effort and worsened the patient
ventilator interaction.
PMID- 17039355
TI - The pharmacological effects of ozone on isolated guinea pig tracheal
preparations.
AB - Ozone is a potent oxidizing agent with a variety of potential uses, including its
antimicrobial and deodorising properties. The recent increased use of ozone led
to questions regarding its safety in humans. This study specifically focussed on
the in vitro effect of ozone on isolated guinea pig tracheal tissue as well as
its effect on the isolated trachea in the presence of various drugs with well
known effects, including methacholine and isoproterenol. The results found in
this study identified two direct effects on the isolated trachea due to ozone
exposure: (1) a definite contraction of the isolated trachea immediately after
exposure to ozone, and (2) a clearly visible and significant hyper responsiveness
of the isolated trachea to irritants, e.g. methacholine. Although ozone has a
negative effect on the trachea, it was concluded that ozone has no adverse effect
on muscarinic receptors. We found that ozone has a significant desensitizing
effect on the pharmacological response of beta sympathomimetics (isoproterenol),
while isoproterenol itself has a relaxing effect on the ozone-induced contraction
of the isolated trachea. Observations in this in vitro study further emphasised
that ozone does have a negative effect on respiratory health. It is underlined
that the inhalation of ozone should be avoided by workers who are often in
contact with the gas, and especially by those with existing airway diseases. An
apparent EC(50) value of ozone on the trachea was established by two different
methods as 5.71 and 9.78 x 10(-3 )M, respectively.
PMID- 17039356
TI - Comparative effects of selective and non-selective nitric oxide synthase
inhibition in gentamicin-induced rat nephrotoxicity.
AB - Different nitric oxide synthase (NOS) isoforms are found in the kidney. Some
studies provided evidences that increased endothelial NOS (eNOS) activity leads
to restoration of renal function after injury, but activation of inducible NOS
(iNOS) aggravates renal failure. In the present study, the beneficial effects of
selective iNOS blockade in gentamicin (GM) induced nephrotoxicity have been
investigated. Four groups of rats were studied. Untreated control rats received
saline. In GM group, GM was injected (IV, 4 mg kg(-1)). In GM + L-NAME group rats
received L-NAME (N-omega-L-arginine methyl ester, a non-selective NOS inhibitor)
simultaneously with GM (IV, 30 mg kg(-1)). Additional doses of L-NAME were
administered 2 and 4 h after GM (IP, 30 mg kg(-1)). In GM + L-NIL group rats were
treated by N-imino-ethyl lysine (L-NIL, a selective iNOS inhibitor). First dose
(IV, 3 mg kg(-1)) administrated simultaneously with GM. Next doses (IP, 3 mg kg(
1)) were administered 2 and 4 h after GM. In all groups, serum and urine
creatinine levels were measured. Creatinine clearance was calculated and
considered as an estimation of glomerular filtration rate (GFR). Urine N-acetyl-b
D-glucose aminidase (NAG) activities were also determined. After experiments,
kidney sections were histologically studied. Selective iNOS inhibition by L-NIL
prevented the GM-induced decrease in GFR and increase in creatinine levels, while
complete non-selective NOS inhibition by L-NAME aggravated the GFR reduction,
elevation of creatinine levels and enzyme release (P < 0.05). Histological
studies showed that GM-treated kidneys had evidences of tubular damages and these
damages were less evident by the administration of L-NIL. In conclusion,
selective inhibition of iNOS may prevent GM-induced nephrotoxicity, whereas non
selective inhibition of NOS aggravates it.
PMID- 17039357
TI - Adaptation of postural orientation to changes in surface inclination.
AB - We previously showed that standing on an inclined surface resulted in an after
effect of leaning in many healthy, blindfolded subjects when they returned to
standing on a horizontal surface (Kluzik et al. in Exp Brain Res 162:474-489,
2005). The direction of leaning depended on the direction of prior surface
inclination, always in a direction that preserved the relative alignment between
the body and the support surface. For example, subjects leaned forward after they
stood on a toes-up-inclined surface. In the present study, we investigated how
the amplitude of surface inclination affected postural muscle activity, joint
position, body segment orientation, and body center of mass (CoM) and foot center
of pressure (CoP) locations before, during, and after subjects stood on an
inclined surface. We asked whether the mechanism that underlies the lean after
effect involves regulation of local postural variables, such as the position of
the ankle joint or the level of muscle activity, or whether instead, the
mechanism involves regulation of global, whole-body postural variables that can
only be determined by multisensory processing, such as orientation of the trunk
or the body's CoM. In one experiment, we found that varying the amplitude of a
toes-up surface inclination between 2.5 degrees and 10 degrees had a systematic,
linear, effect on the post-incline orientation of the trunk and head, but did not
systematically affect the post-incline orientation of the legs, position of the
ankle joint, the level of EMG activity, or the location of the CoP. In a second
experiment, we found that preventing the legs from leaning in the post-incline
period did not abolish leaning of the upper body. These findings suggest that (1)
the body-to-support-surface relationship is an important reference for the CNS
internal representation of postural orientation which is subject to adaptive
modification and (2) the adaptive mechanism underlying the post-incline after
effect of leaning acts at the level of global, whole-body postural variables.
PMID- 17039358
TI - Fatigue-induced adaptive changes of anticipatory postural adjustments.
AB - To examine the fatigue-induced adaptive changes (e.g., timing) of anticipatory
postural adjustments (APAs), APAs of 30 research participants were recorded
before (baseline) and after (post-test) conditions of either rest (control group,
n=15) or fatigue (fatigue group, n=15). Muscle fatigue was generated using a dead
lift exercise performed to exhaustion. Self-initiated postural perturbations were
induced using a rapid unilateral arm-raising maneuver (focal movement), and APAs
were obtained using electromyography (EMG) recorded bilaterally in the lumbar and
thoracic paraspinal muscles as well as the hamstring muscles. Postural stability
during the focal movement was assessed using a force plate. Results showed that
fatigue had no effect on postural stability during the focal movement, and yet
caused earlier APA onsets in three of the six muscles evaluated. In spite of
early APA activation, the APA EMG integrals of two of the three postural control
muscles which exhibited fatigue-induced early APA onsets (T9 and L4 contralateral
paraspinals) did not differ between baseline and post-test measures. The findings
suggest that early APA onset may enhance postural stability by permitting a
longer duration APA which can counteract fatigue-induced decreases in the force
producing capability of muscles that contribute to postural stability.
PMID- 17039360
TI - Two new Ig VH gene families in Oncorhynchus mykiss.
AB - Genes encoding the immunoglobulin heavy-chain variable region (Ig VH) in rainbow
trout (Oncorhynchus mykiss) have been grouped into 11 families. While obtaining a
baseline assessment of the various gene families utilized by trout in the
production of secreted antibody, we discovered two new families. These proposed
Ig VH families, Families XII and XIII, were rarely observed; only two VH sequence
types were detected for each new family, suggesting that they may not be commonly
used in response to antigens, or that the captive environment may not lead to
typical exposures seen in the wild. Additionally, unlike preceding studies, we
found at least one representative gene sequence for each of the 11 reported Ig VH
gene families, possibly indicating that the repertoire of trout Ig VH gene
families may be more universal among different stocks than previously realized.
PMID- 17039359
TI - PEG as a tool to gain insight into membrane fusion.
AB - Thirty years ago, Klaus Arnold and others showed that the action of PEG in
promoting cell-cell fusion was not due to such effects as surface absorption,
cross-linking, solubilization, etc. Instead PEG acted simply by volume exclusion,
resulting in an osmotic force driving membranes into close contact in a
dehydrated region. This simple observation, based on a number of physical
measurements and the use of PEG-based detergents that insert into membranes,
spawned several important areas of research. One such area is the use of PEG to
bring membranes into contact so that the role of different lipids and fusion
proteins in membrane fusion can be examined in detail. We have summarized here
insights into the fusion mechanism that have been obtained by this approach. This
evidence indicates that fusion of model membranes (and probably cell membranes)
occurs via severely bent lipidic structures formed at the point of sufficiently
close contact between membranes of appropriate lipid composition. This line of
research has also suggested that fusion proteins seem to catalyze fusion in part
by reducing the free energy of hydrophobic interstices inherent to the lipidic
fusion intermediate structures.
PMID- 17039362
TI - Adrenal Castleman's disease.
PMID- 17039361
TI - Characterization of swine leukocyte antigen polymorphism by sequence-based and
PCR-SSP methods in Meishan pigs.
AB - Resource herds of swine leukocyte antigen (SLA)-characterized pigs are an
important tool for the study of immune responses, disease resistance, and
production traits. They are also valuable large animal models for biomedical
research, such as transplantation. The Meishan breed of pig is an economically
significant breed that is available at several research institutions in the
United States. We have characterized the SLA polymorphism of the breeding stock
in the herd maintained at the University of Illinois and developed a simple assay
to SLA type individuals within that herd. We have used a reverse transcription
polymerase chain reaction (RT-PCR)-based SLA typing method to clone and DNA
sequence 19 SLA alleles at three SLA class Ia (SLA-1, SLA-2, and SLA-3) and two
SLA class II (SLA-DRB1 and SLA-DQB1) loci. Based on this sequence information, a
rapid SLA typing assay was developed to discriminate each allele using PCR with
sequence-specific primers (PCR-SSP). Using this method, we were able to
characterize the entire Meishan breeding stock and identify four SLA haplotypes
present in the herd. The combination of SLA typing by cloning and DNA sequencing
with PCR-SSP is therefore a valuable tool for the characterization of SLA alleles
and haplotypes in resource herds of pigs.
PMID- 17039363
TI - Use of ziprasidone in patients with fibromyalgia: a case series.
AB - Atypical antipsychotics may be useful in chronic pain treatment. The objective of
the present study was to assess the effect of ziprasidone in fibromyalgia
management. Ziprasidone was administered to 32 fibromyalgia patients at a dose of
20 mg/day, subsequently adjusted according to clinical response and tolerability.
Fibromyalgia Impact Questionnaire (FIQ), Pittsburgh Sleep Quality Index (PSQI), a
Clinical Global Impression improvement scale (CGIi), and a scale evaluating the
severity of fibromyalgia symptoms were administered at 4 week intervals for 12
weeks. Drug adverse reactions were recorded. Ten patients withdrew from the
study. The CGIi showed 32% of responders. FIQ and PSQI scores showed a non
statistically significant decrease. The conditions of stiffness, anxiety and
sadness improved significantly. Most frequent side effects included sleep
disturbances, headache, tremor, and rigidity. Although ziprasidone does not seem
an especially useful adjunct drug in fibromyalgia, it could be tried on patients
who are markedly anxious and/or depressed.
PMID- 17039364
TI - CT urography: a comparison of strategies for upper urinary tract opacification.
AB - A consensus is yet to be reached regarding the best strategy for ensuring maximum
ureteric delineation during CT urography (CTU). In this study we have compared
various CTU protocols to try to establish the best method for ureteric
delineation. Saline infusion in the supine position, saline infusion in the prone
position, furosemide administration (10 mg, iv) and buscopan administration (20
mg iv) with saline infusion in the prone position were tried in four groups, each
having 15 patients who were undergoing CTU. The pelvicalyceal system and ureter
were divided into six segments, to each of which an opacification score was
assigned (0, unopacified segment; 1, less than 50% opacified segment; 2, 50-99%
of the segment opacified; or 3, completely opacified segment) and the results
compared. Furosemide administration resulted in complete opacification of 93% of
the ureters (28 of 30). In the distal (below the sciatic notch) ureter, the mean
score with furosemide was 2.9, while that with saline, supine and prone
positioning was 1.87 and 1.83, respectively, and this difference was highly
significant (P = 0.0002 and P = 0.0001). It was also significantly higher than
the buscopan group (score 2.3, P = 0.002). Also in the lower (the iliac crest to
the sciatic notch) and upper (above the iliac crest) ureter, furosemide had
significantly higher scores than saline infusion in either position. Saline
infusion in the supine and prone positions had very similar scores in all
segments that were less than the buscopan group, but this difference was not
statistically significant. During CT urography, furosemide administration in low
doses is the most effective and convenient technique for ureteric opacification.
PMID- 17039365
TI - Association of left renal vein variations and pelvic varices in abdominal MDCT.
AB - The aim of this study was to determine whether left renal vein (LRV) variation is
associated with pelvic varices and left ovarian vein (LOV) reflux. Routine
abdominal multidetector-row computed tomography scans of 324 women without
symptoms of pelvic congestion syndrome were analyzed. Presence and type of LRV
variants (circumaortic [CLRV] or retroaortic [RLRV]) were recorded. Diameters of
the LRV, ovarian veins (OVs), and parauterine veins were measured and a specific
LRV diameter ratio was calculated for each patient. Presence and severity of
pelvic varices and LOV reflux were noted. Pelvic varices were detected in 59
(18%) of the total of 324 women, in 7 (37%) of the 19 women with RLRVs, in 7
(29%) of the 24 women with CLRVs, and in 45 (16%) of the 281 women with normal
LRVs. The frequency of pelvic varices in the women with LRV variation was
significantly higher than that in the group with normal LRV anatomy (33 vs. 16%;
p=0.009). The frequency of pelvic varices in the women with RLRVs was also
significantly higher than that in the group with normal LRV anatomy (p=0.02). LRV
diameter ratio was correlated with presence of pelvic varices and presence of LOV
reflux (p=0.0001 for both). This study revealed an association between pelvic
varices and LRV variations in a population of predominantly multiparous women.
PMID- 17039366
TI - Exercise training effects on premenstrual distress and ovarian steroid hormones.
AB - Preliminary studies suggest that moderate physical activity may reduce both
premenstrual distress (PD) and the ovarian steroid hormones, progesterone and
estradiol, which have been implicated in PD. We attempted to replicate these
findings, while exploring possible relationships between hormone levels and PD.
In a cross-sectional study, 20 moderate exercisers and 34 sedentary women
completed PD symptom questionnaires and collected urine samples, daily,
throughout a complete menstrual cycle. PD was calculated as the difference in
symptom scores reported during the average of the 4 days prior to menses and the
average of the 4 days closest to mid-cycle. Urine samples taken from the last
quarter of the menstrual cycle were analyzed for urinary estrone glucoronide
(E1G) and pregnanediol glucoronide. In a prospective study the same measures were
used with 14 sedentary women before and after a 24-week moderate exercise
training program. In the cross-sectional study, exercising women reported lower
Pain symptoms, and had lower peak E1G levels than did sedentary women. The
baseline PD symptoms loneliness, crying, and skin blemishes with were
statistically significantly and positively correlated with pregnanediol
glucoronide levels in the cross-sectional study. In the prospective study,
exercise reduced the global PD symptom score, including the Water Retention and
Pain scales, and reduced pregnanediol glucoronide and peak E1G levels. Moderate
aerobic exercise may lessen both PD symptoms and late luteal phase ovarian
hormone levels. An exercise program may benefit women with progesterone-related
premenstrual affect disturbance.
PMID- 17039368
TI - Molecular and biochemical characterization of two brassinosteroid
sulfotransferases from Arabidopsis, AtST4a (At2g14920) and AtST1 (At2g03760).
AB - Mammalian sulfotransferases (EC 2.8.2) are involved in many important facets of
steroid hormone activity and metabolism. In this study, Arabidopsis AtST4a and
AtST1 were identified and characterized as brassinosteroid sulfotransferases that
appear to be involved in different aspects of hormone regulation. The two
proteins share 44% identity in amino acid sequence, and belong to different plant
sulfotransferase families. AtST4a was specific for biologically active end
products of the brassinosteroid pathway. The enzyme sulfated brassinosteroids
with diverse side-chain structures, including 24-epibrassinosteroids and the
naturally occurring (22R, 23R)-28-homobrassinosteroids. AtST4a belongs to a small
subfamily of sulfotransferases having two other members, AtST4b and -c. Among the
three recombinant enzymes, only AtST4a was catalytically active with
brassinosteroids. Transcript expression of AtST4 subfamily members was largely
specific to the root. AtST4b- and -c transcript levels were induced by treatment
with trans-zeatin, while AtST4a was repressed under the same conditions,
supporting a divergent function of AtST4a. Co-regulation of AtST4b and -c
correlated with their location in tandem on chromosome 1. AtST1 was
stereospecific for 24-epibrassinosteroids, with a substrate preference for the
metabolic precursor 24-epicathasterone, and exhibited catalytic activity with
hydroxysteroids and estrogens. To gain more insight into this dual activity with
plant and mammalian steroids, enzymatic activities of human steroid
sulfotransferases toward brassinosteroids were characterized. The
dehydroepiandrosterone sulfotransferase SULT2A1 displayed catalytic activity with
a selected set of 24-epibrassinolide precursors, including 24-epicathasterone,
with specific activities comparable to that measured for the endogenous substrate
dehydroepiandrosterone. The comparable activity profiles of AtST1 and SULT2A1
suggest a similar architecture of the acceptor-binding site between the two
enzymes, and may potentially reflect a common ability to conjugate certain
xenobiotics.
PMID- 17039369
TI - Accumulation of multiple-repeat starch-binding domains (SBD2-SBD5) does not
reduce amylose content of potato starch granules.
AB - This study investigates whether it is possible to produce an amylose-free potato
starch by displacing the amylose enzyme, granule-bound starch synthase I (GBSSI),
from the starch granule by engineered, high-affinity, multiple-repeat family 20
starch-binding domains (SBD2, SBD3, SBD4, and SBD5). The constructs were
introduced in the amylose-containing potato cultivar (cv. Kardal), and the
starches of the resulting transformants were compared with those of SBD2
expressing amylose-free (amf) potato clones. It is shown that a correctly sized
protein accumulated in the starch granules of the various transformants. The
amount of SBD accumulated in starch increased progressively from SBD to SBD3;
however, it seemed as if less SBD4 and SBD5 was accumulated. A reduction in
amylose content was not achieved in any of the transformants. However, it is
shown that SBDn expression can affect physical processes underlying granule
assembly, in both genetic potato backgrounds, without altering the primary
structure of the constituent starch polymers and the granule melting temperature.
Granule size distribution of the starches obtained from transgenic Kardal plants
were similar to those from untransformed controls, irrespective of the amount of
SBDn accumulated. In the amf background, granule size is severely affected. In
both the Kardal and amf background, apparently normal oval-shaped starch granules
were composed of multiple smaller ones, as evidenced from the many "Maltese
crosses" within these granules. The results are discussed in terms of different
binding modes of SBD.
PMID- 17039367
TI - The peroxisomal ABC transporter family.
AB - This review describes the current state of knowledge about the ABCD family of
peroxisomal half adenosine-triphosphate-binding cassette (ABC) transporters.
ABCDs are predicted to be present in a variety of eukaryotic organisms, although
at present, only ABCDs in the yeast Saccharomyces cerevisiae, the plant
Arabidopsis thaliana, and different mammalian species have been identified and
characterized to any significant extent. The functional role of none of these
ABCDs has been established definitively and awaits successful reconstitution of
ABCDs, either as homo- or heterodimers into liposomes, followed by transport
studies. Data obtained in S. cerevisiae suggest that the two ABCDs, which have
been identified in this organism, form a heterodimer, which actually transports
acyl coenzyme A esters across the peroxisomal membrane. In mammals, four ABCDs
have been identified, of which one [adrenoleukodystrophy protein (ALDP)] has been
implicated in the transport of the coenzyme A esters of very-long-chain fatty
acids. Mutations in the gene (ABCD1) encoding ALDP are the cause of a severe X
linked disease, called X-linked adrenoleukodystrophy. The availability of mutant
mice in which Abcd1, Abcd2, or Abcd3 have been disrupted will help to resolve the
true role of the peroxisomal half-ABC transporters.
PMID- 17039370
TI - Inhibition of lycopene cyclase results in accumulation of chlorophyll precursors.
AB - Free porphyrins and their magnesium complexes, including chlorophylls, are potent
photo-sensitizers. Plants usually accumulate these compounds bound to proteins
together with protective compounds like carotenoids. Besides their protective
role, carotenoids can play a structural role in these complexes. To analyze the
effect of impaired carotenogenesis on plastid membranes we applied to barley
seedlings the bleaching herbicide 2-(4-chlorophenylthio)triethylamine (CPTA) as a
specific inhibitor for the cyclization of lycopene. To avoid interference with
photo-oxidation, the essential experiments were performed on seedlings grown in
darkness. While the amount of total carotenoids decreased, we found accumulation
of more 6-carotene than lycopene in darkness clearly showing that CPTA inhibits
the lycopene beta-cyclase more effectively than the lycopene epsilon-cyclase. The
CPTA treatment resulted in accumulation of non-photoactive protochlorophyllide a;
the amount of photoactive protochlorophyllide and NADPH:protochlorophyllide
oxidoreductase remained constant. Further, the level of Mg protophorphyrin and
its monomethyl ester increased to an extent similar to that obtained by
application of 5-aminolevulinic acid (ALA). The perturbation of the
ultrastructure of etioplast inner membranes, observed after CPTA-treatment, was
not found after ALA-treatment; this excluded the accumulated tetrapyrroles as
responsible for the perturbation. By contrast, the down-regulation of Lhcb and
RbcS genes found after CPTA-treatment was compatible with the presumed role of Mg
protophorphyrin as "plastid signal" for regulation of nuclear gene expression.
Possible mechanisms for enhancement of tetrapyrrole accumulation by non-cyclic
carotenoids are discussed.
PMID- 17039372
TI - The effects of ultraviolet radiation on photosynthetic performance, growth and
sunscreen compounds in aeroterrestrial biofilm algae isolated from building
facades.
AB - The effects of artificial ultraviolet radiation [UVR; 8 W m(-2) ultraviolet-A
(UVA), 0.4 W m(-2) ultraviolet-B (UVB)] on photosynthetic performance, growth and
the capability to synthesise mycosporine-like amino acids (MAAs) was investigated
in the aeroterrestrial green algae Stichococcus sp. and Chlorella luteoviridis
forming biofilms on building facades, and compared with the responses of two
green algae, from soil (Myrmecia incisa) and brackish water (Desmodesmus
subspicatus). All species exhibited decreasing quantum efficiency (Fv/Fm) after 1
3 days exposure to UVR. After 8-12 days treatment, however, all aeroterrestrial
isolates exhibited full recovery under UVA and UVA/B. In contrast, D. subspicatus
showed only 80% recovery after treatment with UVB. While Stichococcus sp. and C.
luteoviridis exhibited a broad tolerance in growth under all radiation conditions
tested, M. incisa showed a significant decrease in growth rate after exposure to
UVA and UVA/B. Similarly D. subspicatus grew with a reduced rate under UVA, but
UVA/B led to full inhibition. Using HPLC, an UV-absorbing MAA (324 nm-MAA) was
identified in Stichococcus sp. and C. luteoviridis. While M. incisa contained a
specific 322 nm-MAA, D. subspicatus lacked any trace of such compounds. UV
exposure experiments indicated that all MAA-containing species are capable of
synthesizing and accumulating these compounds, thus supporting their function as
an UV-sunscreen. All data well explain the conspicuous ecological success of
aeroterrestrial green algae in biofilms on facades. Biosynthesis and accumulation
of MAAs under UVR seem to result in a reduced UV-sensitivity of growth and
photosynthesis, which consequently may enhance survival in the environmentally
harsh habitat.
PMID- 17039371
TI - Secretion marker proteins and cell-wall polysaccharides move through different
secretory pathways.
AB - The building up of the cell wall is tightly dependent on the functionality of the
secretory pathway. Syntaxins as well as other SNARE proteins play important roles
during vesicle secretion and fusion. We have compared the secretion of newly
synthesised cell-wall polysaccharides to that of secretory marker proteins such
as secreted green-fluorescent protein (sec-GFP) and secreted rat preputial beta
glucuronidase (secRGUS) in leaf protoplasts and roots of wild-type and transgenic
Nicotiana tabacum plants, overexpressing a syntaxin homologue NtSyr1 (Sp1) and
its soluble variant Sp2 that interferes specifically with Sp1 function, affecting
post-Golgi transport. In protoplasts transiently transformed with secGFP and Sp1,
no variation was observed in the pattern of fluorescence with respect to control;
on the contrary, GFP fluorescence accumulate within the cells in protoplasts co
transformed with secGFP and Sp2. Sp2 reduced the percentage of marker protein
secretion to 53% as quantified with secRGUS. In protoplasts obtained from leaves
of wild-type and transformed tobacco plants expressing Sp1, Sp2 and Sp1 plus Sp2,
no remarkable differences in the percentage of newly synthesised polysaccharides
incorporated into the regenerating cell walls were observed. The same results
were confirmed in roots of whole transformed seedlings. Tests with cytochalasin D
(CD) showed a marked decrease in the amount of newly synthesised polysaccharides
into the wall and a simultaneous sharp increase in membrane-associated
polysaccharides. SecRGUS secretion was also inhibited by CD. The data indicate
that marker proteins and matrix polysaccharides, as well as cellulose synthase
complexes, are secreted through the involvement of different secretory
machineries.
PMID- 17039373
TI - Plant native tryptophan synthase beta 1 gene is a non-antibiotic selection marker
for plant transformation.
AB - Gene transformation is an integral tool for plant genetic engineering. All
antibiotic resistant genes currently employed are of bacterial origin and their
presence in the field is undesirable. Therefore, we developed a novel and
efficient plant native non-antibiotic selection system for the selection of
transgenic plants in the model system Arabidopsis. This new system is based on
the enhanced expression of Arabidopsis tryptophan synthase beta 1 (AtTSB1) and
the use of 5-methyl-tryptophan (5MT, a tryptophan [Trp] analog) and/or CdCl2 as
selection agent(s). We successfully integrated an expression cassette containing
an AtT-SB1 cDNA driven by a cauliflower mosaic virus 35S promoter into
Arabidopsis by floral dip transformation. Transgenic plants were efficiently
selected on MS medium supplemented with 75 microM 5MT or 300 microM CdCl2 devoid
of antibiotics. TSB1 selection was as efficient as the conventional hygromycin
selection system. Northern blot analysis of transgenic plants selected by 5MT and
CdCl2 revealed increased TSB1 mRNA transcript whereas uneven transcript levels of
hygromycin phosphotransferase II (hpt) (control) was observed. Gas chromatography
mass spectrometry revealed 10-15 fold greater free Trp content in AtT-SB1
transgenic plants than in wild-type plants grown with or without 5MT or CdCl2.
Taken together, the TSB1 system provides a novel selection system distinct from
conventional antibiotic selection systems.
PMID- 17039374
TI - Microchemical analysis of laser-microdissected stone cells of Norway spruce by
cryogenic nuclear magnetic resonance spectroscopy.
AB - Stone cells (sclereids) in Norway spruce (Picea abies) bark have been reported to
be highly lignified tissues that are important in physical defence against bark
beetle invasion. Microchemical analyses of the low-molecular weight compounds in
the stone cells of Norway spruce were carried out using laser microdissection in
combination with cryogenic nuclear magnetic resonance and mass spectrometry
(LMD/NMR/MS). Two phenolic compounds, the stilbene astringin and the
dihydroflavonol dihydroxyquercetin 3'-O-beta-D-glucopyranoside, were identified
indicating that stone cells are more than just repositories for lignin. Both of
these compounds were also found to be present in other phloem tissue at a higher
level than in the stone cells based on quantification by cryogenic 1H NMR. Our
results suggest that stone cells may be involved in chemical as well as physical
defense against bark beetles and their associated microorganisms. This paper
reports on the identification of secondary plant metabolites from a single laser
microdissected population of plant cells offering a sensitive new way to
determine the chemical profile of specific plant cell types with a high degree of
precision.
PMID- 17039375
TI - Myogenic progenitor cells in the mouse embryo are marked by the expression of
Pax3/7 genes that regulate their survival and myogenic potential.
AB - The transcription factors Pax3 and Pax7 are important regulators of myogenic cell
fate, as demonstrated by genetic manipulations in the mouse embryo. Pax3 lies
genetically upstream of MyoD and has also been shown recently to directly control
Myf5 transcription in derivatives of the hypaxial somite, where it also plays an
important role in ensuring cell survival. Both Pax3 and Pax7 are expressed in
myogenic progenitor cells derived from the central dermomyotome that make a major
contribution to skeletal muscle growth. In Pax3/Pax7 double mutants, the myogenic
determination genes, Myf5 and MyoD, are not activated in these cells which become
incorporated into other tissues or die. This again demonstrates the dual function
of Pax factors in regulating the entry of progenitor cells into the myogenic
programme and in ensuring their survival. Pax3 expression marks cells in the
dermomyotome that either become myogenic or downregulate Pax3 and assume another
cell fate. The latter include the smooth muscle cells of the dorsal aorta that
share a common clonal origin with the skeletal muscle of the myotome, thus
illustrating the initial multipotency of Pax3 expressing cells.
PMID- 17039376
TI - Molecular characterization and genomic distribution of Isis: a new
retrotransposon of Drosophila buzzatii.
AB - A new transposable element, Isis, is identified as a LTR retrotransposon in
Drosophila buzzatii. DNA sequence analysis shows that Isis contains three long
ORFs similar to gag, pol and env genes of retroviruses. The ORF1 exhibits
sequence homology to matrix, capsid and nucleocapsid gag proteins and ORF2
encodes a putative protease (PR), a reverse transcriptase (RT), an Rnase H (RH)
and an integrase (IN) region. The analysis of a putative env product, encoded by
the env ORF3, shows a degenerated protein containing several stop codons. The
molecular study of the putative proteins coded by this new element shows striking
similarities to both Ulysses and Osvaldo elements, two LTR retrotransposons,
present in D. virilis and D. buzzatii, respectively. Comparisons of the predicted
Isis RT to several known retrotransposons show strong phylogenetic relationships
to gypsy-like elements, particulary to Ulysses retrotransposon. Studies of Isis
chromosomal distribution show a strong hybridization signal in centromeric and
pericentromeric regions, and a scattered distribution along all chromosomal arms.
The existence of insertional polymorphisms between different strains and high
molecular weight bands by Southern blot suggests the existence of full-sized
copies that have been active recently. The presence of euchromatic insertion
sites coincident between Isis and Osvaldo could indicate preferential insertion
sites of Osvaldo element into Isis sequence or vice versa. Moreover, the presence
of Isis in different species of the buzzatii complex indicates the ancient origin
of this element.
PMID- 17039377
TI - Transcriptional analysis between two wheat near-isogenic lines contrasting in
aluminum tolerance under aluminum stress.
AB - To understand the mechanisms of aluminum (Al) tolerance in wheat (Triticum
aestivum L.), suppression subtractive hybridization (SSH) libraries were
constructed from Al-stressed roots of two near-isogenic lines (NILs). A total of
1,065 putative genes from the SSH libraries was printed in a cDNA array. Relative
expression levels of those genes were compared between two NILs at seven time
points of Al stress from 15 min to 7 days. Fifty-seven genes were differentially
expressed for at least one time point of Al treatment. Among them, 28 genes
including genes for aluminum-activated malate transporter-1, ent-kaurenoic acid
oxidase-1, beta-glucosidase, lectin, histidine kinase, and phospoenolpyruvate
carboxylase showed more abundant transcripts in Chisholm-T and therefore may
facilitate Al tolerance. In addition, a set of genes related to senescence and
starvation of nitrogen, iron, and sulfur, such as copper chaperone homolog,
nitrogen regulatory gene-2, yellow stripe-1, and methylthioribose kinase, was
highly expressed in Chisholm-S under Al stress. The results suggest that Al
tolerance may be co-regulated by multiple genes with diverse functions, and those
genes abundantly expressed in Chisholm-T may play important roles in enhancing Al
tolerance. The down-regulated genes in Chisholm-S may repress root growth and
restrict uptake of essential nutrient elements, and lead to root senescence.
PMID- 17039379
TI - Heat wave impacts on mortality in Shanghai, 1998 and 2003.
AB - A variety of research has linked extreme heat to heightened levels of daily
mortality and, not surprisingly, heat waves both in 1998 and in 2003 all led to
elevated mortality in Shanghai, China. While the heat waves in the two years were
similar in meteorological character, elevated mortality was much more pronounced
during the 1998 event, but it remains unclear why the human response was so
varied. In order to explain the differences in human mortality between the two
years' heat waves, and to better understand how heat impacts human health, we
examine a wide range of meteorological, pollution, and social variables in
Shanghai during the summers (15 June to 15 September) of 1998 and 2003. Thus, the
goal of this study is to determine what was responsible for the varying human
health response during the two heat events. A multivariate analysis is used to
investigate the relationships between mortality and heat wave intensity,
duration, and timing within the summer season, along with levels of air
pollution. It was found that for heat waves in both summers, mortality was
strongly associated with the duration of the heat wave. In addition, while
slightly higher than average, the air pollution levels for the two heat waves
were similar and cannot fully explain the observed differences in human
mortality. Finally, since the meteorological conditions and pollution levels for
the two heat waves were alike, we conclude that improvements in living conditions
in Shanghai, such as increased use of air conditioning, larger living areas, and
increased urban green space, along with higher levels of heat awareness and the
implementation of a heat warning system, were responsible for the lower levels of
human mortality in 2003 compared to 1998.
PMID- 17039378
TI - The Bradyrhizobium japonicum Fur protein is an iron-responsive regulator in vivo.
AB - The Fur protein is a global regulator of iron metabolism in many bacterial
species. However, Fur homologs from some rhizobia appear not to mediate iron
dependent gene expression in vivo. Here, transcriptional profiling analysis
showed that more than one-fourth of the genes within the iron stimulon of
Bradyrhizobium japonicum were aberrantly controlled by iron in a fur mutant.
However, Fur has only a modest role in regulating iron transport genes.
Quantitative real time reverse transcriptase PCR measurements confirmed abnormal
gene expression in iron-limited cells of the fur strain, thereby demonstrating
that Fur must function under those conditions. The findings show that B.
japonicum Fur is involved in iron-dependent gene expression, and support the
conclusion that rhizobial Fur proteins have novel functions compared with well
studied model systems.
PMID- 17039380
TI - "Laying on of hands" improves well-being in patients with advanced cancer.
AB - GOAL OF WORK: To determine whether the impact of "laying on of hands" on the well
being of patients with advanced cancer is more efficient when performed by a
person with self-declared "healing powers" as compared to an actor mimicking the
healer in close detail. MATERIALS AND METHODS: A total of 80 patients were
registered to participate in a randomized, single-blind phase III trial to
evaluate the difference in efficacy of "laying on of hands" by either a "healer"
or an actor. Each group consisted of 40 patients, scheduled to receive treatment
for 5 min, three times a week. The effect of treatment was measured using a "Well
Being scale", with the difference of the average score of the "Well-Being scale"
on day 10 being defined as primary and that on day 5 as secondary endpoint. MAIN
RESULTS: There was no significant difference in average score values between the
"healer" and the actor with regard to the primary (p = 0.34) or the secondary
endpoint (p = 0.94), but the comparison was limited due to major protocol
violations by the "healer" who unblinded his status after the first run and quit
the study. The study was completed by the actor as a descriptive, explorative
study on the impact of "laying on of hands". A significant improvement in
symptoms after treatment was found on day 5 (p < 0.001) and on day 10 (p =
0.0002). CONCLUSION: "Laying on of hands" resulted in a significant improvement
of cancer- or cancer-therapy-associated symptoms. The magnitude of improvement
obtained was similar whether on a self-declared-healer- or an actor-provided
"treatment".
PMID- 17039381
TI - Levorphanol: the forgotten opioid.
AB - BACKGROUND: Levorphanol (levo-3-hydroxy-N-methylmorphinan) is a strong opioid
that is the only available opioid agonist of the morphinan series. Levorphanol
was originally synthesized as a pharmacological alternative to morphine more than
40 years ago. It is considered a step-3 opioid by the World Health Organization
(WHO) and has a greater potency than morphine. Analgesia produced by levorphanol
is mediated via its interactions with mu, delta, and kappa opioid receptors.
Levorphanol is also an N-methyl-D-aspartate (NMDA) receptor antagonist. There is
evidence that levorphanol may inhibit uptake of norepinephrine and serotonin.
Similar to morphine, levorphanol undergoes glucuronidation in the liver, and the
glucuronidated products are excreted in the kidney. Levorphanol can be given
orally, intravenously, and subcutaneously. OBJECTIVE: This article reviews the
pharmacodynamics, pharmacology, and clinical efficacy for this often overlooked
step-3 opioid. CONCLUSION: The long half-life of the drug increases the potential
for drug accumulation. Levorphanol has clinical efficacy in neuropathic pain.
PMID- 17039382
TI - Computer analysis of the safety of using three different pedicular screw
insertion points in the lumbar spine in the Chinese population.
AB - To help decide the best starting point for lumbar spine pedicle screw insertion
in the Chinese population using three different techniques (Roy-Camille, Magerl,
and Du). Three-dimensional CT reconstructions were created from 40 adult lumbar
vertebral segments. Three different starting points for lumbar pedicle screw
insertion were used. The direction of the pedicle screw through each hole was
simulated on three-dimensional reconstructed images. Precise CT measurements were
made to assess the distance from the simulated screw and the medial and lateral
pedicle walls at the smallest transverse section of each pedicle. To measure a
pedicle transverse section angle (TSA) lines were drawn on a CT scan in the
direct axis of the pedicle, tangential to the medial, and separately lateral,
walls of the pedicles at the isthmus. The angle these lines made with an anterior
to posterior line, which directly bisected the mid-portion of the vertebral body
was called the TSA. The greater the difference between the TSA between the medial
and lateral walls provides the greatest flexibility for the insertion angle of
the pedicle screw. Additionally, the distance from a line drawn in the direct
central axis of the pedicle was measured from the point of exit from the pedicle
to the entry point of each of three insertion techniques (Du, Mageral, and Roy
Camille), to help understand potential risk factors. There were statistically
significant differences between the distances from the entrance point to the
direct pedicle axis among the three methods (P < 0.001). Du's insertion point was
the shortest from L1 to L4. The distances measured following Magerl's technique
were shortest at L5 (P < 0.05). There was no significant difference of the safe
range of the TSA between the three methods from L1 and L2 (P > 0.05), but
significant differences at L3, L4, and L5 (P < 0.05). At L3 and L4 the safe
ranges of TSA using Du and Magerl's methods were significantly larger than those
measured by Roy-Camille (P < 0.05). At L5 the safe ranges of TSA for the Magerl
technique were the greatest among the three methods (P < 0.05). These results
demonstrate that Du's method provides the safest starting point to place pedicle
screws from L1 to L4, as its distance from the entrance point to the pedicle axis
is the shortest and the safe range of TSA the largest of the three techniques.
Magerl's technique can be safely used in the pedicles from L3 to L5, and is the
safest choice at L5. Roy-Camille's technique is most applicable at L1 and L2, but
has the highest risk when applied from L3 to L5.
PMID- 17039383
TI - New chromogenic and fluorogenic reagents and sensors for neutral and ionic
analytes based on covalent bond formation--a review of recent developments.
AB - To date, hydrogen bonding and Coulomb, van der Waals and hydrophobic interactions
are the major contributors to non-covalent analyte recognition using ionophores,
ligands, aptamers and chemosensors. However, this article describes recent
developments in the use of (reversible) covalent bond formation to detect analyte
molecules, with special focus on optical signal transduction. Several new
indicator dyes for analytes such as amines and diamines, amino acids, cyanide,
formaldehyde, hydrogen peroxide, organophosphates, nitrogen oxide and nitrite,
peptides and proteins, as well as saccharides have become available. New means of
converting analyte recognition into optical signals have also been introduced,
such as colour changes of chiral nematic layers. This article gives an overview
of recent developments and discusses response mechanisms, selectivity and
sensitivity.
PMID- 17039384
TI - Achieving interlocking nails without using an image intensifier.
AB - Interlocking nails are commonly performed using an image intensifier. These are
expensive and are not readily available in most resource-poor countries of the
world. The aim of this study was to achieve interlocking nailing without the use
of an image intensifier. This is a prospective descriptive analysis of 40
consecutive cases seen with shaft fractures of the humerus, femur, and tibia.
Fracture fixation was done using Surgical Implant Generation Network (SIGN)
nails. Forty limbs in 34 patients were studied. There were 12 females and 22
males, giving a ratio of 1:2. The mean age (years) was 35.75+/-13.16 and the
range was 17-70 years. The studied bones were: humerus 10%, femur 65%, and tibia
25%. The fracture lines were: transverse 40%, oblique 15%, and communited 45%.
Fracture grades were: closed 90%, grade I, 5%, grade II, 2.5%, and grade IIIA,
2.5%. Surgical approaches were: antegrade 62.5% and retrograde 37.5%. Indications
for fixation were: recent fracture 92.5%, non-union 5%, and malunion 3%. Methods
of reductions were: open 85% and closed 15%. The mean follow-up period (years)
was 1.50+/-0.78. The union time averaged 3 months. Complication was mainly screw
loosening due to severe osteoporoses in one case. It is, therefore, concluded
that, with the aid of external jigs and slot finders, interlocking can be
achieved without an image intensifier.
PMID- 17039385
TI - Paediatric thoracic tumours presenting as empyema.
AB - Ultrasonography (US) is considered to be adequate for the preoperative evaluation
of childhood empyema. This study was aimed to improve awareness that paediatric
intra-thoracic tumours can mimic childhood post-pneumonic empyema and highlights
the value of computed tomogram (CT) scan with intravenous (IV) contrast in
preoperative evaluation of childhood empyema. The data were analysed on eight
children (four boys and four girls) presented at the median age of 6.2 years (1.8
15 years) for the management of empyema and later confirmed to have intra
thoracic tumours. Intra-thoracic tumours in 8 (5.3%) children out of 150 cases of
post-pneumonic empyema were managed during the study period. All eight had
clinical features, increased white cell count, raised inflammatory markers and
biochemical parameters suggestive of childhood empyema. Chest X-ray showed
localised opacity in 3/8 while in other five suggested significant pleural
collection with mediastinal shift. Additional investigations in referring
hospital were suggestive of empyema in four children; US in three, CT scan
without IV contrast in one. Referring hospital carried out non-diagnostic
thoracocentesis in four children with blood stained pleural tap in two. In four
children corroborative evidence suggestive of infection within pleural cavity and
acute respiratory distress led to an emergency mini-thoracotomy resulting in
significant intra-operative bleeding in two children. Histology on biopsy of the
infected material showed primitive neuroectodermal tumour (PNET) in one,
pleuropulmonary blastoma in one, metastatic malignant melanoma in one and
cytology of pleural fluid diagnosed lymphoma in one. Pre-operative CT scan with
IV contrast in four children correctly identified underlying intra-thoracic
tumour (two benign teratoma, two PNET). In two cases CT with IV contrast was
performed because chest X-ray suggested mediastinal loculated empyema while in
other two high clinical index of suspicion prompted preoperative evaluation with
CT scan with IV contrast. We advocate caution and increased awareness before
considering therapeutic options in childhood empyema and recommend preoperative
CT scan with IV contrast in some selected and unusual cases.
PMID- 17039386
TI - Hemorrhoidopexy staple line height predicts return to work.
AB - PURPOSE: Previous studies identified reduction in pain and complications with
stapled hemorrhoidopexy relative to conventional hemorrhoidectomy. Previously,
the presence of resected squamous epithelium and a staple line height <20 mm
above the dentate line were predictive of postoperative pain. The purpose of this
study was to further investigate and refine the role of staple height in the
prediction of postoperative outcomes. METHODS: From July 2002 to October 2004, 75
patients with symptomatic Grade 3 and 4 mixed hemorrhoids underwent stapled
hemorrhoidopexy in two teaching institutions with prospective data collection.
All procedures were performed under the direct supervision of two colorectal
teaching staff. The majority were performed under monitored anesthesia care as
outpatient procedures. Preoperative, intraoperative, and postoperative patient
characteristics were evaluated. This included demographics, staple line height,
specimen histology, complications, days to return to work, duration of narcotic
pain medicine, and preoperative/postoperative tone and seepage. The results were
subjected to statistical analysis using t-test and ANOVA. RESULTS: Seventy-five
patients with a median age of 49 (range, 25-87) years were identified. Histology
identified 62 specimens with columnar and/or transitional cells, 10 with squamous
epithelium, and 3 with muscle present. Overall complication rate was 14 percent.
Complications included three readmissions for pain control, three acute
postoperative anal fissures, two postoperative bleeds (with one requiring
examination under anesthesia without intervention), one patient with subcutaneous
emphysema, and one admission for fecal impaction. Staple line height was not a
statistically significant predictor of postoperative complication. Median return
to work was 14 (range, 1-31) days. Median duration of narcotic use was six
(range, 0-40) days. Patients with a staple line height>22 mm required a
significantly shorter duration of narcotic pain management (P=0.024). Median
follow-up was 24 (range, 9-253) days. Staple line heights below 20 mm had a mean
return to work of 15 days. A staple line height>20 mm had a mean return to work
of nine days. Staple line height was inversely related to return to work
(P=0.01). CONCLUSIONS: A hemorrhoidopexy staple line>or=22 mm above the dentate
line correlates with a significantly shorter need for postoperative narcotics
(P=0.024) and an earlier return to work (P=0.017). Staple line distance above the
dentate line meaningfully impacts comfort-based outcomes.
PMID- 17039387
TI - Perforated rectal cancer associated with neoadjuvant radiotherapy: report of four
cases.
PMID- 17039388
TI - Innovative effect of illite on improved microbiological conversion of L-tyrosine
to 3,4 dihydroxy phenyl L-alanine (L-DOPA) by Aspergillus oryzae ME2 under acidic
reaction conditions.
AB - In the present investigation, the previous ultraviolet irradiated mutant strain
of Aspergillus oryzae UV-7 was further improved in terms of 3,4 dihydroxy phenyl
L-alanine (L-DOPA) activity after chemical mutagenesis through 1-methyl 3-nitro 1
nitroso guanidine (MNNG = 250-1500 microg/ml) treatment (0-30 min). Among several
mutant variants, the one that produced a larger amount of L-DOPA from L-tyrosine
was designated to as ME2 and it was made 2-deoxy-D-glucose-resistant by growing
it at various concentrations of 2 dg (0.01-0.025 %, w/v) in Vogel's agar medium.
Relatively better production of L-DOPA (> 0.60 mg/ml) was obtained when 2.0%
(w/v) glucose was used as a carbon source in the mycelium production medium and
the tyrosinase activity increased constitutively (1.08 mg/ml), which resulted in
a greater production of L-DOPA. At optimum pH0 (pH 6.0) and reaction time (60
min), more than 65% sugar was utilized for cell mass formation. The maximum
conversion of L-tyrosine to L-DOPA (0.428 mg/ml) was achieved 60 min after the
biochemical reaction. Mould mycelium was used for microbiological conversion of L
tyrosine to L-DOPA because tyrosinases, beta-carboxylases, and tyrosine
hydroxylases are intracellular enzymes. The effect of illite (1.0 x 10(6)-6.0 x
10(6) M) on biochemical conversion of L-tyrosine to L-DOPA by Aspergillus oryzae
ME(2 )was also carried out. Best results of L-DOPA biosynthesis were observed
when the concentration of illite was 3.5 x 10(-6) M (1.686 mg/ml L-DOPA produced
with 1.525 mg/ml consumption of L-tyrosine). It was noted that the addition of
illite not only increased enzyme activity but also enhanced the permeability of
cell membrane to facilitate the secretion of enzymes into the reaction broth. The
comparison of kinetic parameters showed the ability of mutant to yield L-DOPA
(i.e., Yp/x 7.360 +/- 0.04 mg/mg). When the culture grown on various illite
concentrations was monitored for Qp, Qs, and qp, there was significant
enhancement (p < 0.025) in these variables over the control, which indicate that
the study can be commercially applicable on stirred and magnetic rotary drums.
Overall, there was up to 3-fold (Qp = 0.290 mg/L-DOPA produced/ml/h) enhancement
in the product formation rate, which is highly encouraging (HS, LSD 0.456).
PMID- 17039389
TI - Directions of change in land cover and landscape patterns from 1957 to 2000 in
agricultural landscapes in NW Spain.
AB - The aim of this work is the analysis of the dynamics in cultural landscapes,
focused on the spatial distribution of changes in land cover and landscape
patterns, and their possible linkages. These dynamics have been analyzed for the
years 1957 and 2000 in a sector of the north of Galicia (NW Spain) characterized
with diverse landscapes. Afforestation processes linked to agriculture
abandonment and forestry specialization were the main processes observed in the
study area, with the exception of the southern mountainous sector that was
dominated by ploughing of scrubland for conversion into grassland, reflecting a
specialization in livestock production. The structural changes that have taken
place in most of the study area were related to the heterogeneity aspects,
although the mountainous sectors were characterized by changes in heterogeneity
and fragmentation. According to the tests performed, the comparison of the
spatial distribution of both dynamics showed a certain statistical significance,
reflecting the interrelationship between patterns and processes. This approach
could be useful for the identification of areas with similar characteristics in
terms of spatial dynamics so as to define more effective and targeted landscape
planning and management strategies.
PMID- 17039390
TI - Policy windows, policy change, and organizational learning: watersheds in the
evolution of watershed management.
AB - Employing in-depth, elite interviews, this empirical research contributes to
understanding the dynamics among policy windows, policy change, and
organizational learning. First, although much of the research on agenda setting
how issues attract enough attention that action is taken to address them-has been
conducted at the national scale, this work explores the subnational, regional
scale. With decentralization, regional-scale environmental decision-making has
become increasingly important. Second, this research highlights the role of
policy windows and instances of related organizational learning identified by
natural resources managers. Having practitioners identify focusing events
contrasts with the more typical approach of the researcher identifying a
particular focusing event or events to investigate. A focusing event is a sudden,
exceptional experience that, because of how it leads to harm or exposes the
prospect for great devastation, is perceived as the impetus for policy change.
PMID- 17039391
TI - A Water Quality Index applied to an international shared river basin: the case of
the Douro River.
AB - A Water Quality Index (WQI) is a numeric expression used to evaluate the quality
of a given water body and to be easily understood by managers. In this study, a
modified nine-parameter Scottish WQI was used to assess the monthly water quality
of the Douro River during a 10-year period (1992-2001), scaled from zero (lowest)
to 100% (highest). The 98,000 km(2) of the Douro River international watershed is
the largest in the Iberian Peninsula, split between upstream Spain (80%) and
downstream Portugal (20%). Three locations were surveyed: at the Portuguese
Spanish border, 350 km from the river mouth; 180 km from the mouth, where the
river becomes exclusively Portuguese; and 21 km from the mouth. The water
received by Portugal from Spain showed the poorest quality (WQI 47.3 +/- 0.7%);
quality increased steadily downstream, up to 61.7 +/- 0.7%. In general, the water
quality at all three sites was medium to poor. Seasonally, water quality
decreased from winter to summer, but no statistical relationship between quality
and discharge rate could be established. Depending on the location, different
parameters were responsible for the episodic decline of quality: high
conductivity and low oxygen content in the uppermost reservoir, and fecal
coliform contamination downstream. This study shows the need to enforce the
existing international bilateral agreements and to implement the European Water
Quality Directive in order to improve the water quantity and quality received by
the downstream country of a shared watershed, especially because two million
inhabitants use the water from the last river location as their only source of
drinking water.
PMID- 17039392
TI - Prognostic indicators for patients undergoing cytoreductive surgery and
perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal
mesothelioma.
AB - BACKGROUND: This study evaluates clinical, radiological and histopathological
prognostic indicators for survival of patients undergoing cytoreductive surgery
and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal
mesothelioma (DMPM). METHODS: Sixty-two consecutive patients with DMPM underwent
cytoreduction and perioperative intraperitoneal chemotherapy at the Washington
Cancer Institute. Twenty-six clinical, radiological and histopathological
parameters were analyzed in univariate and multivariate analyses using overall
survival as an endpoint. RESULTS: The overall survival was 79 months (range 1-143
months), with 1-, 3- and 5-year survival rates of 84%, 58% and 50%, respectively.
The following 14 prognostic variables were significant for survival in the
univariate analysis: gender (P = .045), peritoneal cancer index (P = .038),
completeness of cytoreduction score (P = .010), interpretive CT findings of the
small bowel and mesentery (P = .001), mesothelioma cell type (P < .001),
mesothelioma nuclear size (P < .001), nuclear/cytoplasmic ratio (P < .001),
mitotic count (P < .001), atypical mitosis (P < .001), chromatin pattern (P <
.001), cellular necrosis (P < .001), perineural invasion (P = .037), stroma
pattern (P < .001) and depth of invasion (P = .014). In the multivariate
analysis, the only factor that was independently associated with an improved
survival after cytoreduction and perioperative intraperitoneal chemotherapy was
mesothelioma nuclear size. CONCLUSIONS: Mesothelioma nuclear size was the
dominant factor determining overall survival in patients with DMPM. A
histopathological staging system based on measurement of the nuclear size was
proposed.
PMID- 17039393
TI - Which screening strategy using BMD measurements would be most cost effective for
hip fracture prevention in elderly women? A decision analysis based on a Markov
model.
AB - INTRODUCTION: Hip fractures are responsible for excessive mortality, decreasing
the 5-year survival rate by about 20%. From an economic perspective, they
represent a major source of expense, with direct costs in hospitalization,
rehabilitation, and institutionalization. The incidence rate sharply increases
after the age of 70, but it can be reduced in women aged 70-80 years by
therapeutic interventions. Recent analyses suggest that the most efficient
strategy is to implement such interventions in women at the age of 70 years. As
several guidelines recommend bone mineral density (BMD) screening of
postmenopausal women with clinical risk factors, our objective was to assess the
cost-effectiveness of two screening strategies applied to elderly women aged 70
years and older. METHODS: A cost-effectiveness analysis was performed using
decision-tree analysis and a Markov model. Two alternative strategies, one
measuring BMD of all women, and one measuring BMD only of those having at least
one risk factor, were compared with the reference strategy "no screening". Cost
effectiveness ratios were measured as cost per year gained without hip fracture.
Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY
cohorts. RESULTS: In this model, which is mostly based on observed data, the
strategy "screen all" was more cost effective than "screen women at risk." For
one woman screened at the age of 70 and followed for 10 years, the incremental
(additional) cost-effectiveness ratio of these two strategies compared with the
reference was 4,235 euros and 8,290 euros, respectively. CONCLUSION: The results
of this model, under the assumptions described in the paper, suggest that in
women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry
(DXA) would be more effective than no screening or screening only women with at
least one risk factor. Cost-effectiveness studies based on decision-analysis
trees maybe useful tools for helping decision makers, and further models based on
different assumptions should be performed to improve the level of evidence on
cost-effectiveness ratios of the usual screening strategies for osteoporosis.
PMID- 17039394
TI - Preliminary evidence on existence of transplasma membrane electron transport in
Entamoeba histolytica trophozoites: a key mechanism for maintaining optimal redox
balance.
AB - Entamoeba histolytica, an amitochondriate parasitic protist, was demonstrated to
be capable of reducing the oxidized form of alpha-lipoic acid, a non permeable
electron acceptor outside the plasma membrane. This transmembrane reduction of
non permeable electron acceptors with redox potentials ranging from -290 mV to
+360 mV takes place at neutral pH. The transmembrane reduction of non permeable
electron acceptors was not inhibited by mitochondrial electron transport
inhibitors such as antimycin A, rotenone, cyanide and azide. However, a clear
inhibition with complex III inhibitor, 2-(n-heptyl)-4-hydroxyquinoline-N-oxide;
modifiers of sulphydryl groups and inhibitors of glycolysis was revealed. The
iron-sulphur centre inhibitor thenoyltrifluoroacetone failed to inhibit the
reduction of non permeable electron acceptors whereas capsaicin, an inhibitor of
energy coupling NADH oxidase, showed substantial inhibition. p
trifluromethoxychlorophenylhydrazone, a protonophore uncoupler, resulted in the
stimulation of alpha-lipoic acid reduction but inhibition in oxygen uptake.
Mitochondrial electron transport inhibitors substantially inhibited the oxygen
uptake in E. histolytica. Transmembrane reduction of alpha-lipoic acid was
strongly stimulated by anaerobiosis and anaerobic stimulation was inhibited by 2
(n-heptyl)-4-hydroxyquinoline-N-oxide. Transmembrane redox system of E.
histolytica was also found to be sensitive to UV irradiation. All these findings
clearly demonstrate the existence of transplasma membrane electron transport
system in E. histolytica and possible involvment of a naphthoquinone coenzyme in
transmembrane redox of E. histolytica which is different from that of mammalian
host and therefore can provide a novel target for future rational
chemotherapeutic drug designing.
PMID- 17039395
TI - Potential roles of 3'-5' exonuclease activity of NM23-H1 in DNA repair and
malignant progression.
AB - NM23-H1 is a metastasis suppressor protein that exhibits 3'-5' exonuclease
activity in vitro. As 3'-5' exonucleases are generally required for maintenance
of genome integrity, this activity represents a plausible candidate mediator of
the metastasis suppressor properties of the NM23-H1 molecule. Consistent with an
antimutator function, ablation of the yeast NM23 homolog, YNK1, results in
increased mutation rates following exposure to UV irradiation and exposure to the
DNA damaging agents etoposide, cisplatin, and MMS. In human cells, a DNA repair
function is further suggested by increased NM23-H1 expression and nuclear
translocation following DNA damage. Also, forced expression of NM23-H1 in NM23
deficient and metastatic cell lines results in coordinate downregulation of
multiple DNA repair genes, possibly reflecting genomic instability associated
with the NM23-deficient state. To assess the relevance of the 3'-5' exonuclease
activity of NM23-H1 to its antimutator and metastasis suppressor functions, a
panel of mutants harboring defects in the 3'-5' exonuclease and other enzymatic
activities of the molecule (NDPK, histidine kinase) have been expressed by stable
transfection in the melanoma cell line, 1205Lu. Pilot in vivo metastasis assays
indicate 1205Lu cells are highly responsive to the metastasis suppressor effects
of NM23-H1, thus providing a valuable model for measuring the extent to which the
nuclease function opposes metastasis and metastatic progression.
PMID- 17039396
TI - Nucleoside diphosphate kinase A as a controller of AMP-kinase in airway
epithelia.
AB - This review integrates recent understanding of a novel role for NDPK-A in two
related directions: Firstly, its role in an airway epithelial cell when bound to
the luminal (apical) membrane and secondly in the cytosol of many different cells
(epithelial and non-epithelial) where an isoform-specific interaction occurs with
a regulatory partner, AMPKalpha1. Thus NDPK-A is present in both a membrane and
cytosolic environment but in the apical membrane, its roles are not understood in
detail; preliminary data suggest that it co-localises with the cystic fibrosis
protein (CFTR). In cytosol, we find that NDPK-A is coupled to the catalytic
alpha1 isoform of the AMP-activated protein kinase (AMPKalpha subunit), which is
part of a heterotrimeric protein complex that responds to cellular energy status
by switching off ATP-consuming pathways and switching on ATP-generating pathways
when ATP is limiting. We find that ATP is located within this complex and 'fed'
from NDPK to AMPK without ever 'seeing' bulk solution. Importantly, the reverse
can also happen such that AMPK activity can be made to decline when NDPK-A
'steals' ATP from AMPK. Thus we propose a novel paradigm in NDPK-A function by
suggesting that AMP-kinase can be regulated by NDPK-A, independently of AMP.
PMID- 17039397
TI - Promoting positive adolescent development for at-risk students with a student
assistance program.
AB - This study evaluated the psycho-educational small-group component of the CASPAR
Youth Services Student Assistance Program with a randomized-controlled trial. Two
cohorts of at-risk sixth graders from six schools in two communities were
randomly assigned to intervention or control conditions and tested one and a half
years later at the end of the seventh grade. A generalized estimating equations
model yielded a significant intervention effect on all three composite outcome
variables. The results support the effectiveness of prevention strategies aimed
at promoting positive youth development and a social influence process for
adolescents that creates trusting relationships as the foundation for helping
youth improve key skills, exert greater control over their lives, and make
informed decisions about substances. EDITOR'S STRATEGIC IMPLICATIONS: School
administrators should be aware of this promising approach (pending replication)
of using student assistance counselors to promote children's intrinsic motivation
and potential for positive decision making.
PMID- 17039398
TI - Implementing an evidence-based preventive intervention in neighborhood family
centers: examination of perceived barriers to program participation.
AB - : This study examined parents' perceived barriers to participation in a
multicomponent prevention program implemented by a community agency serving
culturally diverse urban neighborhoods. The Early Risers Participation Interview
(ER-PI), modeled after Kadzin et al.'s (1997) Barriers to Treatment Participation
Scale, was administered to parents (N = 138) of children who were screened for
disruptive behavior and were randomized into a two-year intervention condition.
Results showed that the perceived barriers score provided significant information
in differentiating low and high participators after controlling for child,
parent, and family characteristics. Early identification and resolution of
parents' perceived barriers to participation may be key to implementing
multifaceted preventive programs successfully in inner-city neighborhoods.
EDITOR'S STRATEGIC IMPLICATIONS: The authors present promising practices for
client engagement and retention. The experimental, longitudinal design is
notable, especially in the evaluation of a community-run prevention program.
PMID- 17039399
TI - Images in neuro-oncology: rapid development of osseous and chondrous metaplasia
in recurrent anaplastic ependymoma.
PMID- 17039400
TI - Oligodendroglioma with neurocytic differentiation versus atypical
extraventricular neurocytoma: a case report of unusual pathologic findings of a
spinal cord tumor.
AB - Differentiating oligodendroglioma from extraventricular neurocytoma by
conventional light microscopy alone can present a diagnostic challenge. We report
pathologic findings of an unusual spinal cord tumor from a 33-year-old male
patient which showed hybrid features of oligodendroglioma and extraventricular
neurocytoma. Magnetic resonance imaging (MRI) showed an enhancing intramedullary
mass in the cervicothoracic region (C7 through T6). Histologic examination
revealed a clear cell neoplasm containing ganglion-like cells and calcifications,
prompting the differential diagnosis of oligodendroglioma and extraventricular
neurocytoma. The immunohistochemical analysis disclosed neural differentiation of
the neoplastic cells with strong synaptophysin and neurofilament staining
consistent with extraventricular neurocytoma, as well as strong S-100 and glial
fibrillary acidic protein (GFAP) expression. Molecular studies with fluorescent
in situ hybridization (FISH) revealed chromosome 1p/(partial) 19q deletions, a
finding commonly observed in oligodendroglioma. The proliferation index (using
antibody MIB1) of the tumor was approximately 30%. The morphologic findings and
these results strengthen the hypothesis that these tumors may share a common
progenitor cell, which has also been observed by others. Because there are
differences in patient management and long-term prognosis, it is important to
attempt to distinguish between oligodendroglioma and neurocytoma. This unusual
case and similar rare reported cases support the need to reclassify tumors
showing pathologic features common to both neurocytoma and oligodendroglioma as a
unique entity, while the effort continues to identify the cell of origin.
PMID- 17039401
TI - Increased level of tetrahydro-beta-carboline derivatives in short-term fermented
garlic.
AB - In our previous study [1], we found that relatively short-term spontaneous
fermentation (40 days at 60-70 degrees C, 85-95% relative humidity) potentiates
anti-oxidative properties of garlic, in which scavenging activity against
hydrogen peroxide was included. Since tetrahydro-beta-carboline derivatives
(THbetaCs) that possess hydrogen peroxide scavenging activity have recently been
identified in aged garlic extract, THbetaCs were quantitatively analyzed with
liquid chromatography-mass spectrometry (LC-MS). (1R, 3S)-1-Methyl-1,2,3,4
tetrahydro-beta-carboline-3-carboxylic acid (MTCC) and (1S, 3S)-MTCC were found
in the fermented garlic extract whereas only trace levels of MTCCs were detected
in the row garlic extract. Therefore, it is suggested that relatively short-term
fermentation potentiates scavenging activity of garlic against hydrogen peroxide
by forming THbetaCs, especially MTCCs.
PMID- 17039402
TI - Gender differences in pornography consumption among young heterosexual Danish
adults.
AB - The aims of the study were (1) to investigate gender differences in pornography
consumption among Danish adults aged 18-30 and (2) to examine gender differences
in situational, interpersonal, and behavioral characteristics of pornography
consumption. A national survey study was conducted using a representative sample
of 688 young heterosexual Danish adult men and women. The study found large
gender differences in prevalence rates of pornography consumption and consumption
patterns. Compared to women, men were exposed to pornography at a younger age,
consumed more pornography as measured by time and frequency, and used pornography
more often during sexual activity on their own. Gender differences in the
interpersonal context of use were also evident, with women using pornography more
often with a regular sexual partner than men. In turn, men were found to use
pornography more often on their own or with friends (non-sexual partners) than
women. For both men and women, the usual place of use was home and no significant
gender difference was found in this regard. Men and women were found to vary in
their preferences in pornographic materials, with men both preferring a wider
range of hardcore pornography and less softcore pornography than women. Gender
differences in sexual behavioral factors were limited to masturbation patterns
with men masturbating more than women. Male gender, higher frequency of
masturbation, lower age at first exposure, and younger age were found to account
for 48.8% of the total variance of pornography consumption. The results were
discussed in relation to the sociocultural environment and evolutionary theory.
It is argued that gender differences in social acceptability, adherence to gender
stereotypes, traditions of gender sexuality, gender norms, and mating strategies
are key factors in understanding gender differences in pornography consumption.
PMID- 17039403
TI - Childhood family correlates of heterosexual and homosexual marriages: a national
cohort study of two million Danes.
AB - Children who experience parental divorce are less likely to marry heterosexually
than those growing up in intact families; however, little is known about other
childhood factors affecting marital choices. We studied childhood correlates of
first marriages (heterosexual since 1970, homosexual since 1989) in a national
cohort of 2 million 18-49 year-old Danes. In multivariate analyses, persons born
in the capital area were significantly less likely to marry heterosexually, but
more likely to marry homosexually, than their rural-born peers. Heterosexual
marriage was significantly linked to having young parents, small age differences
between parents, stable parental relationships, large sibships, and late birth
order. For men, homosexual marriage was associated with having older mothers,
divorced parents, absent fathers, and being the youngest child. For women,
maternal death during adolescence and being the only or youngest child or the
only girl in the family increased the likelihood of homosexual marriage. Our
study provides population-based, prospective evidence that childhood family
experiences are important determinants of heterosexual and homosexual marriage
decisions in adulthood.
PMID- 17039405
TI - Family correlates of comorbid anxiety disorders in children with attention
deficit/hyperactivity disorder.
AB - This study evaluated parental anxiety and parenting practices associated with
comorbid Anxiety Disorders among children with Attention Deficit/Hyperactivity
Disorder. Clinic-referred families (n=143) were diagnosed using DSM criteria.
Parents and children completed measures of parenting practices. Comorbid anxiety
in children was significantly associated with maternal anxiety,
overprotectiveness, and a lack of positive parenting. The relative odds of
comorbid anxiety appeared to be especially high when all three factors were
present. These findings are consistent with theory linking those three family
factors to the development of anxiety in all children. Implications for
adjunctive treatment of anxiety that is comorbid with ADHD are discussed.
PMID- 17039404
TI - Phase II study of amrubicin in previously untreated patients with extensive
disease small cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) study.
AB - PURPOSE: To evaluate the efficacy and safety of amrubicin, (+)-(7S, 9S)-9-acetyl
9-amino-7-[(2-deoxy-beta-D-erythro-pentopyranosyl )oxy]-7,8,9,10-tetrahydro-6,11
dihydroxy-5,12-naphthacenedione hydrochloride, in previously untreated patients
with extensive-disease small cell lung cancer (SCLC). PATIENTS AND METHODS: A
total of 35 previously untreated patients with extensive-disease SCLC were
entered into the study. Amrubicin was given by daily intravenous infusion at 45
mg/m(2)/day for 3 consecutive days, every 3 weeks. Unless there was tumor
regression of 25% or greater after the first cycle, or 50% or greater after the
second cycle, treatment was switched to salvage chemotherapy in combination with
etoposide (100 mg/m(2), days 1, 2, and 3) and cisplatin (80 mg/m(2), day 1).
RESULTS: Of the 35 patients entered, 33 were eligible and assessable for efficacy
and toxicity. Of the 33 patients, 3 (9.1%) had a complete response (95%
confidence interval [CI], 1.9-24.3%) and 22 had a partial response, for an
overall response rate of 75.8% (95% CI, 57.7-88.9%). Median survival time was
11.7 months (95% CI, 9.9-15.3 months), and 1-year and 2-year survival rates were
48.5% and 20.2%, respectively. The most common toxicity was hematologic. Non
hematologic toxicity of grade 3 or 4 was only seen in 3 patients with anorexia
(9.1%) and 1 patient with alopecia (3.0%). Salvage chemotherapy was administered
to only 6 patients. CONCLUSION: Amrubicin was active for extensive-disease SCLC
with acceptable toxicity. Further studies in combination with other agents for
SCLC are warranted.
PMID- 17039406
TI - Varicella-Zoster virus gene expression at variable periods following death in a
rat model of ganglionic infection.
AB - We used a rat model of Varicella-Zoster virus (VZV) ganglionic infection, which
mirrors some of the features of VZV latency in humans, to determine the temporal
pattern of expression of a VZV immediate-early gene (63) and a VZV late gene (40)
at 0, 24 and 48 h after death of the animal. The immediate-early VZV gene 63 is
known to be abundantly expressed during human ganglionic latency, while the late
VZV gene 40 is not expressed during human latency. Using both RNA in situ
hybridisation (ISH) and nested RT-PCR, it was found that at all time points in
both thoracic and lumbar ganglia, the number of ganglia positive for VZV gene 63
was higher than for gene 40. The expression of gene 40 did not increase with time
postmortem (pm) These results provide indirect support for the hypothesis that
patterns of expression of VZV genes detected in human tissue at even 48 h pm
reflect the pattern of expression during human ganglionic latency.
PMID- 17039407
TI - Evidence that PTB does not stimulate HCV IRES-driven translation.
AB - It is now well established that Hepatitis C Virus (HCV) translation is driven by
an Internal Ribosome Entry Site (IRES) resulting in cap-independent translation.
Such a mechanism usually occurs with the help of IRES Associated Factors (ITAFs).
Moreover, an important translational feature is likely conserved from the model
of classical mRNA circularisation (5'-3' cross-talk), involving the HCV RNA
highly structured 3' extremity called the 3'X region. This could bind several
cellular factors and modulate the translation efficacy, at least in Rabbit
Reticulocyte Lysate (RRL). In particular, polypyrimidine-binding proteins have
been proposed to be potential HCV ITAFs, such as Polypyrimidine Tract Binding
protein (PTB). However, contradictions still exist as to the role of PTB: its
ability to bind both the HCV IRES and the 3'X region leads to the hypothesis that
it could positively modulate IRES-driven translation in the presence of the X
structure. Results of translational and PTB-binding studies of X mutant sequences
led us to discredit PTB as protagonist of 3'X region stimulation on HCV IRES
driven translation. Moreover, competition assays of X RNA in trans on IRES-driven
translation demonstrate the involvement of at least two stimulating factors and
led to the conclusion that this mechanism is more complex than initially thought.
Although we did not identify these factors, it is no longer doubtful that there
is effectively a stimulating functional interaction between the HCV IRES and the
3'X region in RRL.
PMID- 17039408
TI - A comparison of complete untranslated regions of measles virus genomes derived
from wild-type viruses and SSPE brain tissues.
AB - We compared complete untranslated regions (UTRs) of two subacute sclerosing
panencephalitis (SSPE) measles virus (MV) strains and two wild-type (wt) MV
strains, all belonging to the same genotype (D6). In comparison to wt MVs of the
same genotype, base changes were identified in the two SSPE measles virus strains
at 27 and 33 noncoding positions, respectively. Majority of these residues are
unique for each of the SSPE virus sequences in comparison to all other reported
measles virus strain sequences. The location of some of these changes indicates
that they may modify cis-acting regulatory sequences including gene-end signal of
the P gene, H/L gene junction and Kozak consensus element of the L gene. Further,
within the long UTR between M and F genes, deletions and insertions were
identified. Thus, our study could be significant for additional investigation
using reverse genetics and recombinant viruses, of possible influence of
mutations in UTRs on establishment and maintenance of chronic progressive CNS
disease caused by MV persistence.
PMID- 17039409
TI - Maintenance of the rat transgenic model of familial amyotrophic lateral sclerosis
expressing human SOD1G93A mutation.
AB - A colony of transgenic rats expressing the human mutant Cu,Zn superoxide
dismutase gene (hSOD1G93A) that is associated with some cases of familial form of
amyotrophic lateral sclerosis (ALS) has been maintained in the Animal House of
the Polish Academy of Sciences Medical Research Centre since 2003. This
transgenic model, generated by Howland et al. (Proc Natl Acad Sci USA 2002; 99:
1604-1609), has been obtained under the material transfer agreement from Wyeth
Corporation. The transgenic SOD1G93A (or 'Howland') rats develop neurological and
neuropathological symptoms reminiscent of human ALS, i.e. progressive loss of
motoneurons leading to paralysis and death. This paper describes maintenance of
the transgenic rat colony, and general procedures used in experiments with these
animals (i.e. genotyping, neurological observations, anaesthesia, etc.). At the
beginning of the colony, up to the 3rd generation of the rats, symptoms of the
model disease appeared at 95-125 days of age, and the animals survived till 120
145 days of age. Thereafter a gradual change in the disease phenotype occurred,
and in the 8th generation approximately 1/3 of the rats displayed much slowed
disease progression.
PMID- 17039410
TI - Morphological changes and selective loss of motoneurons in the lumbar part of the
spinal cord in a rat model of familial amyotrophic lateral sclerosis (fALS).
AB - Morphological alterations and the course of changes in motoneuron counts were
studied by light microscopy (cresyl violet staining) in the L2/L3 region of the
spinal cord of hemizygotic transgenic rats carrying the amyotrophic lateral
sclerosis-associated mutant human gene for Cu,Zn superoxide dismutase (hSOD1G93A)
and of their non-transgenic littermates. In 60-day old transgenic rats, a few
ischaemic-looking alpha-motoneurons and occasional vacuolization and accumulation
of tigroid in some of the cells were apparent. On day 93 of life more distinct
cellular pathology was found in transgenic rats, including moderate gliosis,
neuronophagy of alpha-motoneurons, and occasional neuronophagy of gamma
motoneurons. In 120-day-old transgenic rats, abundant gliosis and profound
neuronophagy of alpha-motoneurons were observed combined with occasional
neuronophagy of other cells. Some loss of alpha-motoneurons was also apparent in
120-day-old non-transgenic littermates of the transgenic rats. No difference in
alpha-motoneuron and gamma-motoneuron counts was found between the rats on day 60
of life (early presymptomatic stage of the model disease in the transgenic rats).
At 93 days of age (late presymptomatic stage), alpha-motoneuron count, but not
gamma-motoneuron count, tended to be lower (p=0.06) in the transgenic rats. On
day 120 of life (symptomatic stage), alpha-motoneuron count in the transgenic
rats was about half that in their nontransgenic littermates (p<0.001); at this
time point the relative decline in alpha-motoneuron number in the former was 57%
(day 120 versus day 60; p<0.001). A smaller decline in alpha-motoneuron count was
also found in nontransgenic rats (day 120 vs day 60: 24%, p<0.05); this was not
associated with the emergence of neurological symptoms or distinct changes in the
cell morphology of the spinal cord region studied.
PMID- 17039411
TI - Progression of morphological changes within CNS in a transgenic rat model of
familial amyotrophic lateral sclerosis.
AB - An analysis of the dynamics of histological and immunocytochemical changes in the
CNS of a transgenic rat model of fALS in various periods of life was performed.
Material was obtained from animals on the 60th day of age (4), 93rd day of age
(3) and 120th presymptomatic day and from 3 animals in paretic stage of the
disease. Formalin-fixed and paraffin-embedded slices were stained with HE and
Kluver-Barrera method. Immunoreactions to GFAP, S-100, ferritin, neurofilament,
ubiquitin, synaptophysin and tau protein were also performed. Within the brain
tissues patchy neuronal loss and dark or ischaemic neurons were dispersed in
cortical layers, CA1, CA3 and CA4 hippocampal areas and structures of the
hemispheres and brain stem. In the spinal cord, numerous alpha motoneurons were
dark or ischaemic. Vacuoles or small pale spots were visible in their cytoplasm.
Microspongiosis surrounded some motoneurons, particularly cells subjected to
neuronophagy. Neuronophagy, sporadically observed at the age of 60th day, was
more extensive on the 93rd day of age, and at the age of 120 days already
involved all interneurons of the anterior and posterior horns. In the immune
reaction to neurofilament numerous fibres, often thick, fragmented or rosary
like, were observed. They were located within subcortical white matter, external
and internal capsules, anterior horns of the spinal cord. Changes became more
intensive with age. Astrocytic reactivity was weak in animals on the 60th and
93rd day of life. Non-numerous cells were immunoreactive to GFAP and S-100,
although an increase of astrocytic nuclei was observed. On the 120th day of age
and in symptomatic stage astrocytic hypertrophy and proliferation were intensive.
But from the 60th day of age ubiquitin and tau protein immunopositive material
was accumulated in the perinuclear area of astroglial cytoplasm. Immunoreaction
of nerve cells to these proteins was negative. CONCLUSIONS: 1) In the subclinical
stage of the disease the pathological process within the CNS takes place already
on the 60th day of age and its intensity increases with age. 2) Morphological
changes are not limited to motor neuronal cells. Various structures of the CNS
are damaged. 3) Weak astroglial reaction probably depends on pathological
accumulation of ubiquitin and tau protein in cytoplasm. 4) Astroglial cells are
probably also a "target" for pathogenic factors in the rat model of fALS.
PMID- 17039412
TI - Ultrastructural changes in lumbar spinal cord in transgenic SOD1G93A rats.
AB - The purpose of this study was to determine structural changes which trigger the
onset and progression of amyotrophic lateral sclerosis in rats expressing a human
SOD1 transgene with mutation G93A. Lumbar spinal cord of affected rats in early
and late presymptomatic (PM, 60 and 93 days of age) and symptomatic (S, 120 days
of age) stage of the disease were analyzed ultrastructurally. At 60 days the
structure of lumbar spinal cord as well as alpha motoneurons type S and F
appeared normal; however, careful examination revealed that approximately 15% of
axons were filled with mitochondria that were abnormal in number, size and
morphology. Grossly swollen mitochondria with disrupted cristae were a prominent
feature in all large axons at 93 days of age. At this time swelling and dilated
mitochondria were observed also in type S motoneurons, while type F had small,
well preserved mitochondria. At symptomatic stage the alpha motoneurons showed
moderate neuronal loss, mainly of the S type. The most interesting finding at
this stage was the occurrence of motoneurons with morphological signs of
apoptotic-like degeneration. Such apoptotic-like motoneurons were characterized
by nuclear and cytoplasmic condensation, chromatin compaction and formation of
uniformly dense, dark structures. Numerous axons with very dark, compact interior
as well as apoptotic bodies were irregularly scattered throughout the neuropil.
Our ultrastructural study indicates that dying motoneurons in transgenic mutant
SOD1G93A rats exhibit reminiscent apoptotic morphology which is preceded by
significant mitochondrial abnormalities mainly in proximal axons and S
motoneurons. Different reaction of slow and fast motoneurons to degenerating
factors requires further analysis.
PMID- 17039413
TI - Astroglial alterations in amyotrophic lateral sclerosis (ALS) model of slow
glutamate excitotoxicity in vitro.
AB - Chronic excitotoxicity mediated through defective glial and/or neuronal glutamate
transport may contribute to several neurodegenerative diseases including
amyotrophic lateral sclerosis (ALS). This study was performed to determine the
ultrastructural characteristics of astroglial changes concomitant with motor
neuron (MN) degeneration in a model of slow excitotoxicity in vitro. The study
was performed on organotypic cultures of rat lumbar spinal cord subjected to the
glutamate uptake blockers threohydroxyaspartate (THA) and L-trans-pyrrolidine-2,4
dicarboxylate (PDC). The chronic inhibition of glutamate transport by THA and PDC
resulted in slow degeneration of the rat's MNs accompanied by distinct glial
changes predominantly involving protoplasmic astrocytes. The presence of
irregular vacuoles and vesicles in the astroglial cells was frequently observed.
Occasionally the astrocytes exhibited proliferation and accumulation of abnormal
profiles of smooth endoplasmic reticulum. In 3 weeks there were no signs of
increased production of glial filaments in the protoplasmic astrocytes. The
results evidenced the coexistence of neuronal degeneration and astroglial
abnormalities in an ALS model in vitro and suggested an active role of astrocytes
contributing to the induction and propagation of MN degeneration.
PMID- 17039414
TI - Auto-antibodies against proteins of spinal cord cells in cerebrospinal fluid of
patients with amyotrophic lateral sclerosis (ALS).
AB - Aetiology and pathogenesis of amyotrophic lateral sclerosis (ALS) is still a
mystery. Among several hypotheses autoimmune mechanisms are also taken into
account. We report here our investigations of auto-antibodies against proteins of
spinal cord cells in the cerebrospinal fluid (CSF) and serum of ALS patients. The
results were correlated with the severity of disease course. The subjects were 57
ALS patients (29 severe, 28 mild) and 10 normal controls. The major finding in
CSF was the presence of antibodies against a 70 kD protein in the majority of ALS
patients. This protein was identified as neurofilament 68. The second protein of
high reactivity and frequency of appearance was a 82 kD protein, which was
identified as a-actinin. Less reactive and less frequent were antibodies directed
against 55 kD and 40 kD proteins. They were immunologically defined to be related
to desmin and actin, resp. The difference between the reactivity of anti
neurofilament and anti-desmin related protein in the severe and mild ALS groups
was significant. More frequent were the anti-neurofilament antibodies in the
severe ALS cases as compared to the milder ones. In normal CSF, antibodies
directed against 55 kD, 70 kD and 82 kD proteins were present in traces and
appeared in 5%, 20% and 10% of cases, respectively. In the serum of 30% of severe
ALS patients traces of antibodies against 70 kD protein were detected. The
morphological studies in the presence of CSF of ALS patients revealed pronounced
immunoreactivity of spinal cord neurons, mainly within anterior horns. The
significance of the presence of auto-antibodies in CSF of ALS patients against
cellular proteins of the spinal cord is hard to define. It is conceivable that
they appear as a secondary immunological consequence of neuronal death. It is
also possible that they may accelerate the course of neuronal degeneration.
PMID- 17039415
TI - Does the ganglion of Ribes exist?
AB - Some have included the ganglion of Ribes (Francois Ribes, 1765-1845), lying on
the anterior communicating artery, as the most superior ganglion of the
sympathetic nervous system. To verify the presence of this structure, the
anterior communicating artery was harvested from 40 fresh adult cadavers and
histological analysis and immunochemistry performed. Grossly and with
magnification, no ganglion-like structures were found in or around the anterior
communicating artery in any specimen. However, scattered neuronal cell bodies
were found in the adventitia of the anterior communicating artery with
histological immunochemical analysis. Based on the lack of vasoactive intestinal
peptide staining and the positive reaction to tyrosine hydroxylase, these neurons
are most likely sympathetic in nature. Based on our findings, a grossly visible
ganglion of Ribes does not exist. However, neuronal cell bodies were found in the
adventitia of the anterior communicating artery although the function of such
cells remains speculative.
PMID- 17039416
TI - The brain immune response in human prion diseases. Microglial activation and
microglial disease. I. Sporadic Creutzfeldt-Jakob disease.
AB - A study of microglial activation and its contribution to the CNS immune response
was performed on the brain autopsy material of 40 patients with definite sporadic
Creutzfeldt-Jakob disease (sCJD). Spatial patterns of microglial activation and
prion protein disease-associated (PrPd) deposition were compared in cerebellar
and cerebral cortices using immunohistochemical (IHC) activation markers.
Morphological phenotype forms of microglial cells in activation stages were
assessed immunohistochemically (IHC). The immune inflammatory response dominated
by microglia was found to be a characteristic feature in CJD. Differences in the
intensity and patterns of microglial activation corresponded to variable patterns
of PrP deposition, whereas the morphological phenotype forms of microglia were
specific for activation stages. The presence of activated microglial cells in the
various activation stages regardless of illness duration indicates continuous
microglial activity and microglial contribution to the spread of infection for
the whole symptomatic period of the disease. Remarkable vacuolar degeneration
changes of numerous microglial cells in different activation stages including
homing stage may suggest dysfunction of microglial immune surveillance in human
sCJD that can significantly contribute to transmissible spongiform encephalopathy
(TSE) pathogenesis.
PMID- 17039417
TI - Activation of Akt and Erk pathways in medulloblastoma.
AB - Medulloblastoma (MB) is the most common malignant brain tumour in children. Its
aetiology is unknown, although several signalling pathways controlling cell
proliferation are thought to participate in the progress of the neoplasm.
Mutations of the genes encoding proteins participating in the pathways triggered
by embryonic growth factors like Sonic hedgehog (Shh) or WNT are often found in
MB. Another model of MB development is overexpression or mutation of several
types of growth factor receptors, including IGF-IR, EGF-R and PDGFR, that have
the ability to activate cellular kinases responsible for promoting cell
proliferation. In order to test this hypothesis, in the current paper we tested
the activation of two kinases, Akt/PKB (protein kinase B) and Erk (extracellular
signal-regulated kinase) and their substrates in 10 sporadic medulloblastoma
cases. We show that MBs are a highly heterogeneous group of tumours that show
upregulation of various signalling pathways. Nevertheless, both Akt and Erk may
contribute to the progression of MB, triggering, at least in some cases, the mTOR
(mammalian target of rapamycin) pathway, controlling translation of several cell
cycle-related proteins. We hypothesize that Akt and Erk activation may also be
associated with downregulation of protein phosphatase 2A (PP2A).
PMID- 17039418
TI - The role of trkB receptor in the formation of post-traumatic neuroma.
AB - The outcome of peripheral nerve injury is often impaired by post-traumatic
neuroma developing at the injury site. Neuroma is usually accompanied by
neuropathic pain, which is usually resistant to most analgesics and presents a
serious clinical problem. The mechanisms underlying post-traumatic neuroma remain
unclear, but they are likely associated with regeneration processes. Brain
derived neurotrophic factor (BDNF) and its receptor, trkB, are strongly
implicated in axonal regeneration after injury. The aim of this work was to
examine the role of trkB in post-traumatic neuroma formation. The sciatic nerve
was transected in wild-type and heterozygous trkB-deficient mice. The nerve was
either left cut or immediately sewn up or the gap injury model was performed. The
gap was provided with an autologous or cross (obtained from another genetic
group) graft. Sixteen weeks after surgery, the animals were sacrificed and
histologic evaluations were performed. We found very limited or no neuroma
formation in wild-type animals, regardless of the surgical procedure. In the
majority of trkB-deficient mice, the post-traumatic neuroma was found at the end
of the proximal stump of the transected nerve. In the gap injury model, in trkB
deficient animals receiving wild-type graft, there was no neuroma at the join
site between the graft and distal stump of the nerve. In contrast, if the graft
was autologous, neuroma formed at both joints. We also noticed many more mast
cells accumulated at the surgery site in trkB-deficient than in wild-type
animals. These results indicate the important role of BDNF receptor in post
traumatic neuroma formation.
PMID- 17039419
TI - The role of the extracellular calcium-sensing receptor in health and disease.
AB - The calcium-sensing receptor has a key role in calcium homeostasis, it is
involved in the regulation of the serum calcium level within minutes via the
secretion and action of parathyroid and the excretion of calcium in the kidney in
a negative feedback manner. Mutations of the calcium sensing receptor gene leads
to inactivating and activating mutations resulting in diseases with
hypercalcaemia and hypocalcaemia. The loss of function mutations are associated
with familial benign hypocalciuric hypercalcaemia (FHH), an autosomal dominant
disease characterised by lifelong mild hypercalcaemia, low urinary calcium
excretion, and inappropriate high parathyroid hormone levels, sometimes difficult
to distinguish from mild asymptomatic primary hyperparathyroidism. Patients with
FHH did not profit from parathyroidectomy, a calcium lowering therapy is not
necessary. The gain of function mutations of the calcium-sensing receptor are
associated with autosomal dominant hypocalcaemia (ADH), a disease characterised
by a generally asymptomatic hypocalcaemia, inappropriately high urinary calcium
excretion and normal PTH levels. A therapy to raise the serum calcium
concentration has to be done carefully and is only indicated in symptomatic
patients, because of enhancement of hypercalciuria with the risk of
nephrocalcinosis and nephrolithiasis. Molecular genetic analysis of the calcium
sensing receptor gene facilitates the sometimes difficult diagnosis. The
development of compounds modulating the calcium sensing receptor function and
thereby the section of PTH may become an important role in treatment of diseases
of calcium metabolism.
PMID- 17039420
TI - Impact of smoking on the course of Graves' disease after withdrawal of
antithyroid drugs.
AB - Cigarette smoking has been reported to alter relapse rate in patients with
Graves' disease (GD). However, the predictive effect of smoking in GD patients
after withdrawal of antithyroid drug treatment (ATDT) is still controversial. A
prospective multicenter trial has previously identified smoking as an independent
risk factor for relapse. Based on this study, the present paper gives a more
detailed analysis of the impact of smoking on the long-term course of GD after
ATDT withdrawal. To this end, 86 smokers and 177 non-smokers were followed during
two years after ATDT cessation. At the end of ATDT (visit 1) and four weeks later
(visit 2) smokers had significant higher TSH receptor antibody (TRAb) levels than
non-smokers (10.0 IU/L+/-1.6; mean+/-SEM vs. 6.4 IU/L+/-0.9; 11.0 IU/L+/-1.8 vs.
6.8 IU/L+/-0.8, p < 0.01, respectively). During follow-up, Kaplan Meier analysis
showed a significantly higher relapse rate in smokers than non-smokers. A subset
of GD patients with TRAb levels >10 IU/L had the highest risk to develop relapse
during follow-up. Among them, smokers more often relapsed than non-smokers
irrespective of TRAb levels, p < 0.01. Thus, in smokers with TRAb levels > or =10
IU/L the predictive values of a positive and negative test for relapse was 68%
and 73%, respectively (specificity 95%). In conclusion, we identified two effects
by which smoking alters the course of GD. First, smoking is implicated to elevate
TRAb levels and therefore increase the risk for relapse during follow-up. Second,
smoking is an independent risk factor to worsen the clinical course of both, GD
patients with low and high immunological risk to experience relapse after a
successful outcome of ATDT. Thus, our data suggest that smoking has modifying
immunological consequences and an adverse impact on the course of GD after
withdrawal of ATDT. Therefore, patients should be encouraged to stop smoking.
PMID- 17039421
TI - Prevalence of glutamic acid decarboxylase antibody positivity and its association
with insulin secretion and sensitivity in autoimmune thyroid disease: A pilot
study.
AB - OBJECTIVE: Type 1 diabetes and autoimmune thyroid disease are commonly
associated. Few studies have addressed islet-cell autoimmunity and its relation
with glucose homeostasis in Hashimoto's thyroiditis. The aims of this study were:
(1) to determine the prevalence of islet-cell autoimmunity, and (2) to compare
insulin sensitivity and secretion patterns between normal glucose tolerant
glutamic acid decarboxylase antibodies (GA-D-Ab) positive and negative patients
with Hashimoto's thyroiditis. METHODS: Two hundred fifty-three consecutive
patients with Hashimoto's thyroiditis were recruited. After excluding 38 patients
with diabetes mellitus, 215 were screened for presence of GAD-Ab. Nine GAD-Ab
positive and 8 age, sex and body mass index (BMI) matched GAD-Ab negative
patients from the same cohort were included. Frequently sampled intravenous
glucose tolerance tests (FSIGTT) were applied. Using glucose and insulin data
from FSIGTT, fasting glucose to insulin ratio, HOMA-IR and HOMA-beta-cell
function, using the minimal model analysis (MIN-MOD) program, the first phase
insulin secretion in response to glucose, the insulin sensitivity index and
glucose sensitivity index were calculated. RESULTS: Eleven patients were positive
for GAD-Ab (5.1%). There was no difference in any insulin sensitivity or
secretion parameters between the GAD-Ab positive and negative patients.
CONCLUSIONS: Our results suggest that the prevalence GAD-Ab in Hashimoto's
thyroiditis is around 5%. GAD-Ab antibody positivity per se does not appear to be
associated with any disturbances in insulin sensitivity or insulin secretion in
this specific population. The presence of islet-cell autoimmunity does not seem
to influence insulin secretion or action in normal glucose tolerant subjects with
Hashimoto's thyroiditis in this pilot study. Whether the presence of GAD-Ab per
se or along with other antibodies impairs insulin dynamics or predicts the
development of diabetes in autoimmune thyroiditis remains to be determined in
future studies.
PMID- 17039422
TI - Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic
control and lowers body weight in subjects with type 2 diabetes.
AB - AIMS: Effects of the long acting GLP-1 analogue--liraglutide in subjects with
type 2 diabetes. METHODS: 144 type 2 diabetic subjects on metformin treatment
(1000 mg BID) were randomised to 5 weeks of treatment (double-blind) with
metformin plus liraglutide, liraglutide or metformin, or metformin plus
glimepiride (open label). The dose of liraglutide was increased weekly from 0.5
to 2 mg OD. RESULTS: Liraglutide added to metformin monotherapy was associated
with a significant reduction in fasting serum glucose (FSG) (-3.9 mM -4.9; -2.9)
(primary objective), and HbA1c levels (-0.8% -1.2; -0.4). Furthermore,
liraglutide in combination with metformin vs. metformin plus glimepiride
significantly reduced FSG (-1.2 mM -2.2; -0.2). In addition, body weight was
significantly lower in the metformin plus liraglutide vs. the metformin plus
glimepiride group (-2.9 kg -3.6; -2.1). There were no biochemically confirmed
episodes of hypoglycaemia with liraglutide treatment. Nausea was the most
frequently reported adverse event following liraglutide therapy, it was transient
in nature, and led to withdrawal of only 4% of the subjects. CONCLUSIONS: Using a
weekly dose-titration liraglutide is well tolerated up to 2 mg daily. While
liraglutide caused transient gastrointestinal side effects, this rarely
interfered with continuing treatment. An improvement in FSG over that in control
groups was seen for liraglutide as an add-on to metformin. In the latter case,
body weight was reduced in comparison to metformin plus glimepiride. Liraglutide
is a promising drug for the treatment of type 2 diabetes.
PMID- 17039423
TI - An insertion/deletion polymorphism in the alpha2B adrenoceptor gene is associated
with age at onset of type 2 diabetes mellitus.
AB - Alpha2B adrenoceptor (alpha2B-AR) mediates a variety of functions, including
insulin secretion. An insertion/deletion (I/D) polymorphism of the alpha2B-AR
gene located on chromosome 2 has recently been described. The aim of the present
study was to examine if there is a difference in the D allele frequency of
alpha2B-AR gene between type 2 diabetic patients and controls, as well as to
ascertain whether the D allele confers an increased risk for earlier onset of
diabetes. This study included 199 type 2 diabetic patients and 204 age- and sex
matched healthy volunteers. Genotyping of I/D polymorphism was performed by PCR.
No significant difference in the D allele frequency was observed between the two
groups (22.1% vs. 19.1%, p = 0.409). Among type 2 diabetic patients, however,
presence of the D allele was associated with significantly younger age at onset
of diabetes (51.4+/-8.6 vs. 59.2+/-9.7 years, p < 0.001). Multiple stepwise
linear regression identified alpha2B I/D genotype as an independent predictor of
age at onset of DMT2, explaining 14.3% of its variance. This result indicates
that the D allele may be implicated in impaired glucose metabolism leading to
earlier manifestation of diabetes in predisposed subjects.
PMID- 17039424
TI - Evaluation of the diabetic charcot foot by MR imaging or plain radiography--an
observational study.
AB - Magnetic resonance (MR) images and concomitant plain radiographs of 26 Charcot
feet of different stages (stage 0 to III) were reviewed in retrospect for
discordant findings. Bone and joint abnormalities were evaluated qualitatively,
and quantitatively guided by the AO integral classification of injuries of the
foot. MR images revealed traumatic bone and joint injuries (bone oedema, occult
fractures, and joint effusion) already in stage 0, when X-ray still showed normal
bone and joint anatomy (p = 0.02). Moreover, MR images revealed bone oedema,
joint effusion and soft tissue oedema in addition to fractures and calluses in
stage I (bone dissolution), stage II (bone coalescence), and stage III (bone
remodeling), i.e., in stages with overt radiographic pathology. According to this
observational study, MR imaging, in addition to radiography, provides important
information as to the extent and the natural course of bone injury in the
diabetic Charcot foot. MR imaging, thus, may improve disease staging, as well as
treatment monitoring.
PMID- 17039425
TI - Evaluation of tight junction protein 1 encoding zona occludens 1 as a candidate
gene for albuminuria in a Mexican American population.
AB - Albuminuria, a hallmark of diabetic nephropathy, has been shown to be
significantly heritable in multiple studies. Therefore, the identification of
genes that affect susceptibility to albuminuria may lead to novel avenues of
intervention. Current evidence suggests that the podocyte and slit diaphragm play
a key role in controlling the selective sieve of the glomerular filtration
barrier, and podocyte-specific genes have been identified that are necessary for
maintaining its integrity. We therefore investigated the role of gene variants of
tight junction protein (TJP1) which encodes another slit diaphragm-associated
protein zona occludens 1 as risk factors for albuminuria in the San Antonio
Family Diabetes/Gallbladder Study (SAFDGS), which consists of extended Mexican
American families with a high prevalence of type 2 diabetes. Albuminuria, defined
as an albumin (mg/dl) to creatinine (mg/dl) ratio (ACR) of 0.03, which is
approximately equivalent to a urinary albumin excretion (UAE) >30 mg/day, was
present in a total of 14.9% of participants, and 31% had type 2 diabetes. The
TJP1 exons, flanking intronic sequence, and putative proximal promoter regions
were investigated in this population. Twentynine polymorphisms, including 7
nonsynonymous SNPs, were identified and genotyped in all subjects of this study
for association analysis. Three sets of correlated SNPs, which include 3 exonic
SNPs, were nominally associated with ACR (p value range 0.007-0.049); however,
the association with the discrete trait albuminuria was not significant (p value
range 0.094-0.338). We conclude that these variants in TJP1 do not appear to be
major determinants for albuminuria in the SAFDGS; however, they may play a minor
role in its severity in this Mexican-American population. Further examination of
the TJP1 gene region in this and other cohorts will be useful to determine
whether ZO-1 plays a significant role in glomerular permselectivity.
PMID- 17039426
TI - Parathyroid hormone (1-34) augments angiopoietin-1 expression in human osteoblast
like cells.
AB - Parathyroid hormone (PTH) is a major regulatory factor in skeletal physiology.
However, the molecular mechanism underlying the effects of PTH on bones has yet
to be elucidated in detail. Recently, some reports have demonstrated the crucial
role of bone vasculature with regard to bone density. Angiopoietin-1 (Ang-1),
along with VEGF, has been established as a primary angiogenic regulatory agent.
In this study, we have attempted to characterize the effects of PTH (1-34) on Ang
1 expression and signaling molecules, employing primary-cultured human osteoblast
like cells. Quiescent osteoblasts were exposed to PTH (1-34), after which Ang-1
expression was determined at the mRNA and protein levels. Reverse transcription
polymerase chain reaction (RT-PCR) analyses indicated that Ang-1 mRNA expression
increased as the result of PTH (1-34) treatment. The expression of the Ang-1
protein was also augmented as the result of treatment with PTH (1-34). An
adenylyl cyclase activator, forskolin, was shown to induce Ang-1 mRNA expression,
whereas the protein kinase A inhibitor, H-89, blocked the PTH (1-34)-mediated
expression of Ang-1 mRNA. These findings indicate that PTH (1-34)-mediated Ang-1
expression involves adenylyl cyclase-protein kinase A dependent signaling. Our
observations also show that Ang-1 may perform a crucial role in the effects of
PTH (1-34) on bones, possibly involving alterations in bone vasculature.
PMID- 17039427
TI - Cushing's syndrome due to ectopic CRH secretion by adrenal pheochromocytoma
accompanied by renal infarction.
AB - Ectopic production of corticotropin-releasing hormone (CRH) by a pheochromocytoma
is an infrequent cause of Cushing's syndrome. We report the case of a 43-year-old
man with Cushing's syndrome due to a CRH-producing adrenal pheochromocytoma. The
patient had clinical and biochemical evidence of hypercortisolism in conjunction
with high ACTH levels and non-suppressible serum cortisol levels on low-dose and
high-dose dexamethasone suppression testing. In addition to these clinical
features of one month's duration, the patient developed symptoms of
pheochromocytoma including headache, hypertension that was resistant to
conventional therapy and excessive sweating. Biochemical testing confirmed
elevated 24-hour urinary catecholamines and metabolites. Abdominal CT revealed a
4.5 x 4 x 3.5 cm mass in the left adrenal gland. He underwent elective left
adrenalectomy. Light microscopic and immunochemical studies revealed a
pheochromocytoma that contained immunoreactive CRH and was negative for ACTH.
Plasma ACTH and dexamethasone supression tests normalized after surgery. This is
an unusual case of a CRH-secreting pheochromocytoma. This was complicated by
renal infarction, illustrating further the complexity of Cushing's syndrome in a
patient with pheochromocytoma caused by CRH hypersecretion.
PMID- 17039428
TI - [Federal Cross for Merits to Professor Dr. Friedrich Wilhelm Schwartz].
PMID- 17039429
TI - [Possibilities for intervention in depression among adolescents and young adults
from a public health point of view].
AB - When considering measures to decrease the burden of disease that is caused by
depression, the depressive diseases of adolescents and young adults are of
increasing interest. The prevalence in this group is high and an increase in
prevalence has to be considered. The prognosis for juvenile depression is
particularly bad. This review discusses the potentials to influence the burden of
disease through interventions such as therapy, indicated, selective and universal
prevention and health promotion for adolescents and young adults. The most impact
can thereby be expected from an effective treatment of depression and other
mental diseases that have high co-morbidity with depression. There is some
evidence for the effectiveness of preventive interventions for depression,
however, most approaches currently seem to be unsuitable for wide implementation
in the population. However, as open measures, they can offer individual benefit.
Health promotion that focuses on political, living and societal conditions should
be directed at the family. Policy measures that improve the living conditions of
parents also promote the mental health of children. Finally, the discussion about
the burden of disease that is caused by depression should be held by considering
current societal norms. In this context, it is of special interest as to how much
depression and how much loss of function should be still considered as normal and
not eligible for intervention.
PMID- 17039430
TI - [Professional status and development of morbidity of health insurance patients in
the period 1990 to 2003. A longitudinal Analysis of Routine Data from the Gmunder
Ersatzkasse].
AB - In Germany there are only insufficient data both with regard to general morbidity
events as well as with regard to the effects of specific professions on the
morbidity process. For this reason the data of the Gmuender Ersatzkasse (GEK)
have been analysed with a longitudinal design for the period 1990 to 2003. Our
sample includes all employed members of the GEK who had been insured as of
January 1, 1990 and were between 30 and 59 years old at this baseline. The total
sample comprises 129,173 men and 13,567 women. The statistical analysis was
performed with the statistical package "Transitional Data Analysis" (TDA) which
was developed especially for longitudinal data. The analysis includes both
cumulated morbidity rates as well as transition rates (Cox regression). The
analysis shows that the cumulated morbidity rates of the seven diseases are
higher for women than for men in the age category 30-39 years. In the age
categories 40-49 and 50-59 years the cumulated morbidity rates are higher for men
than for women. With regard to the occupations, the highest morbidity rates are
found for manual occupations and services without special skills. The lowest
rates are found for professions with high skills, engineers and managers. The
results of the longitudinal analysis show distinctive social gradients. For
occupations with lower skills the morbidity rates are about 100 percent higher
than those of occupations with higher skills. Longitudinal analyses on the basis
of health insurance fund data can make an important contribution to the
monitoring of health and morbidity and should therefore be conducted also by
other health insurance funds.
PMID- 17039431
TI - [Psychosocial workload, sick leave, and health-related well being: an empirical
study from the perspective of gender research].
AB - PURPOSE: The aim of this study was to test hypotheses on the consequences of
gender role expectations with regard to the extent of work stress, selected
health-related measures and their associations. METHOD: Data on psychosocial
workload (questionnaire of effort-reward imbalance), sick leave (self-reports of
the duration of medically certified sick leave during the past two years) and
health-related well being were collected in a representative sample of German
full-time employees (n = 666). Hypotheses were tested using analyses of variance
(ANOVA) and covariance (ANCOVA) and moderated linear regression analyses.
RESULTS: Women reported lower health-related well-being as compared to men while
effort-reward imbalance and sick leave did not differ between the sexes. Parents
reported slightly longer durations of sick leave during the past two years than
childless participants (not significant). The results of stratified linear
regression analyses show stronger associations between effort-reward imbalance
and both health-related measures for women with children than for men with
children, while single men and women do not differ in this regard. CONCLUSIONS:
Evidence of this kind can be useful for the purposeful planning and
implementation of health promotion measures at work. Women with children would be
a group deserving special attention. The findings also point to continuing
differences in gender role expectations in the family context.
PMID- 17039432
TI - [Working hours and job satisfaction among physicians in hospitals and general
practice in Munich. Results of an anonymous questionnaire].
AB - PURPOSE: In autumn 2004 the local association of physicians (Arztlicher Kreis-
und Bezirksverband Munchen) performed a survey among employed physicians in
Munich on working hours and working conditions. The aim of the study was to
assess the extent to which the German law on working hours is actually
implemented in employed physicians, and to obtain information about their work
satisfaction. METHODS: A questionnaire was sent to all employed physicians in
hospitals and medical practices. Participants were asked to give anonymous
information and send it back per mail. RESULTS: In total, 2450 out of 5461
physicians took part in the survey. 45% reported that their working hours do not
meet the German law on working hours of 1994. 44.4% stated that overtime is not
fully recognized by their employers. 43.5% think the job would become more
attractive if the law was implemented. 63.3% expect an income loss with the
implementation. 53.7% are thinking about quitting their job. For 59.9% the burden
of long working hours is an important reason for this. Women are more likely to
be given a limited employment contract than men, and their overtime is more
rarely recognized in full. CONCLUSION: Many employed physicians in Munich are
dissatisfied with their job. The high burden of long working hours is a main
reason for this.
PMID- 17039433
TI - [Efficacy of an intervention programme on burnout symptoms of partners of
depressed patients].
AB - AIM OF THE STUDY: A newly developed group intervention programme was evaluated
with regard to its effectiveness to decrease the burnout symptoms of the partners
of depressed patients. METHODS: Within a period of six months, a group of 66
persons has taken part in the intervention for a total of twelve group sessions.
A control group consisted of 50 persons without any intervention. Burnout was
assessed using the German version of the Maslach Burnout Inventory (MBI). To
evaluate the time effect, the burnout dimensions were used as independent
variables in random effects models. RESULTS: Over the analyzed period of time no
significant positive effect was measured on any of the assessed burnout
dimensions. CONCLUSIONS: An increased inclusion of depressed patients in the
intervention as well as an increased intensity and a lowering of the admission
threshold for the heavily burdened relatives could increase the effectiveness of
the program.
PMID- 17039434
TI - [Regional mortality differences in Bavaria].
AB - OBJECTIVE: In completion of a decision of the Bavarian Parliament we examined the
regional mortality differences within Bavaria. DATA: The analysis was based on
the number of deaths in Bavaria in the years of 2000-2002. Data on regional
demographic and socioeconomic indicators were used to identify potential
associations. METHODS: Deaths were analysed by cause of death and region. Crude
and age standardised mortality rates were calculated. Additionally, we assessed
the potential years of life lost in order to obtain some indication of the
potential effects of preventive action. The association with likely explanatory
factors was investigated on an ecological level. RESULTS: The regional mortality
differences in Bavaria show a northeast-southwest gradient favouring the
southwest, which reflects the socioeconomic situation within Bavaria. This may be
due to the economic disadvantage northeast Bavaria had to endure as a result of
its marginal location within a divided Europe. We found strong bivariate
correlations of the mortality rate with individual socioeconomic factors (e. g.
with available income: -0.582; with unemployment: +0.416; with the immigration
rate: -0.473). Exploratory analysis suggest that about 50 % of the regional
variation in mortality could be explained by socioeconomic factors. DISCUSSION:
The results for cause of death indicate that behavioural factors in relation to
socioeconomic aspects may well play a role in the mortality gradient. This will
be the focus of a future piece of research of our unit.
PMID- 17039435
TI - [How much do inpatient treated diabetics know about their disease?].
AB - AIM OF STUDY: The aim of the study was to find to find out which factors are able
to predict the disease-specific knowledge of in-patient diabetic patients and to
characterize this group of patients. METHODS: The disease-specific knowledge of
diabetic patients of a Hospital in Munich, Germany (department of diabetology)
was tested using a general questionnaire and a specific diabetes knowledge test.
All data manipulation and statistical calculations were conducted with the
statistical software package SAS (version 9.1). RESULTS: On average type-1
diabetics achieved 73% of the possible points in the knowledge test, type-2
diabetics achieved 68% of total points. In bivariate analyses, using logistic
regression, existence of diabetes related complications was a significant
predictor of poor knowledge (OR = 4.36; 95%-KI: 1.38-13.77) in type-1-diabetics.
Other factors, e. g. lack of diabetes education were associated with low test
results but reached no statistical significance (OR = 6.13; 95%-KI: 0.67-56.42).
In multivariate logistic regression (female) gender was a significant risk factor
for low test results (OR = 7.66; 95%-KI: 1.18-49.8). In type-2-diabetics lack of
diabetes education (OR = 3.86; 95%-KI: 1.51-9.84), low self-assessment of
information about diabetes (OR = 3.90; 95%-KI: 1.36-11.21) and lack of knowledge
about diabetes diet (OR = 4.06; 95%-KI: 1.60-10.28) were predictors of poor test
results. The existence of diabetes related complications was associated with poor
test results but showed no statistical significance in multivariate analysis (OR
= 2.99; 95%-KI: 0.85-10.43). CONCLUSIONS: There is a group of diabetic inward
patients that is less informed about diabetes and shows knowledge deficits in
testing. These patients often lack diabetes education and show an unfavourable
course of the disease, already having diabetes related complications. Type-2
diabetes patients who feel that they have poor information about their disease
actually achieve lower results in knowledge testing. Efforts to assure diabetes
education for these patients are essentially necessary.
PMID- 17039436
TI - [Smoking behavior in adolescents: a comparison of population-representative,
regional or selectively assessed data and implications for prevention].
AB - INTRODUCTION: The prevalence of adolescent smoking underlines the necessity of
preventive measures, which goals are based on representative data. It is not
known whether schools participate in prevention interventions, where smoking
constitutes a relatively big or minor problem. OBJECTIVE: This study examines a
population of adolescents on (a) different smoking variables and (b) compares
them with representative, population based data. METHODS: Survey of n = 324
adolescents of grade 7-10 in 3 schools in Greifswald and surroundings that were
ready to participate in a prevention curriculum. RESULTS: In total, 80% of the
students under examination indicated to have at least tried smoking in their
lifetime. Daily smokers were 31%, 18% were occasional smokers, 39% have indicated
that they hat tried to quit without success. These figures vary across age, grade
and sex. Smoking prevalence is comparable between schools ready to participate in
prevention and regionally assessed data, but much higher than population based
data would have estimated. CONCLUSION: The goal of preventive measures can not be
solely grounded on representative, population-based data, but needs (a) to be
regionally defined and (b) to consider the population actually participating in
such prevention interventions. The readiness to participate is not higher in
schools where smoking constitutes a comparable minor problem. Preventive measures
are applied in schools where the problem is perceived.
PMID- 17039437
TI - [The spread of HIV/AIDS in Ukraine].
AB - BACKGROUND: In the end-year report 2004 of the European Centre for the
Epidemiological Monitoring of AIDS (EuroHIV), the number of newly diagnosed HIV
infections in Ukraine ranks second in the WHO European Region after the Russian
Federation. METHODS: An analysis of the HIV/AIDS reports from the official
epidemiological register of the Ukrainian Centre for AIDS Prevention between 1987
and 2005 was undertaken. In addition, reports from the seroepidemiological
monitoring were utilised. RESULTS: According to the Ukrainian Ministry of Health,
the cumulative number of reported HIV infections by the end of 2005 amounts to
more than 88,900 cases with 13,786 new reports in 2005. The number of newly
registered AIDS cases rose from 45 in 1995 to 4220 in 2005. However, because of
many unreported HIV diagnoses, the actual numbers are presumed to exceed the
official reports considerably. Most of the infections are associated with
injection drug abuse. The second most important route of transmission is sexual
contact, also due to an increase in commercial sex. Vertical transmissions from
infected mothers to their children rank third. CONCLUSION: HIV was not a
significant problem in the Ukraine before 1995. Since 1995 there has been a
considerable increase in the number of newly registered HIV cases. At the
beginning of the epidemic, HIV was mainly transmitted through sexual contacts in
the Ukraine. Since 1995 infected drug users have been the main source of
infection in the spread of the epidemic. Unless effective preventive measures are
taken, and unless there is more investment in development projects, the HIV/AIDS
epidemic in Ukraine could also affect the health system in neighbouring European
countries.
PMID- 17039438
TI - [Associations between bioaerosols coming from livestock facilities and asthmatic
symptoms in children].
AB - Although health effects of occupational exposures to livestock emissions are
known, potential associations between living in the neighbourhood of intensive
livestock facilities and the risk of developing respiratory or allergic diseases
are still under discussion. During routine school entry examinations in selected
rural districts in Lower Saxony we asked parents about respiratory and allergic
symptoms of their 5-6 year old children. A questionnaire with standardised
questions of the ISAAC-Studies for respiratory and allergic symptoms and
corresponding risk factors was used. Complementarily the children were examined
for visible signs of flexural dermatitis and in a subsample the SX1-test was used
as an in vitro test for inhalative IgE mediated sensibilisations in capillary
blood. Individual exposure to bioaerosols (endotoxin, fungi, bacteria and total
dust) coming from livestock facilities was estimated using a Lagrange dispersion
model based on the emission rates and locations of the lifestock facilities. A
total of 7943 questionnaires (response rate over 85%) were analysed, of which
3867 could be used for the correlation analyses between exposition to endotoxin
and asthmatic symptoms. Multivariate logistic regression models were analyzed,
considering an atopic disease of the parents as a potential effect modifier and
not as a confounder. The prevalence of allergic and asthmatic symptoms is similar
to the results of other comparable studies, e. g. "wheezing in the last 12
months" 15.9% for boys and 12.9% for girls. An increase in the prevalence of
asthmatic symptoms for higher endotoxin levels was observed only for children of
atopic parents. The multivariate controlled odds ratio for one unit logarithm
endotoxin concentrations is 1.15, p-value 0.016. Similar effects were observed
for other asthma indicators, but not for subjective criteria of the exposition,
e. g. the distance to the next large livestock facility guesstimated by parents.
Among the overall analysed potential associations between exposition to
bioaerosols and asthmatic and allergic symptoms only a few were statistically
significant. The discussed association between endotoxin and asthmatic symptoms
in predisposed children needs further investigation.
PMID- 17039440
TI - Evaluation of an imidacloprid (8.8% w/w)--permethrin (44.0% w/w) topical spot-on
and a fipronil (9.8% w/w)--(S)-methoprene (8.8% w/w) topical spot-on to repel,
prevent attachment, and kill adult Ixodes scapularis and Amblyomma americanum
ticks on dogs.
AB - This study evaluated the effectiveness of two topical spot-on formulations --
imidacloprid(8.8% w/w)-permethrin (44.0% w/w) and fipronil (9.8% w/w)-(S)
methoprene (8.8% w/w)--to repel, prevent the attachment of, and kill adult Ixodes
scapularis and Amblyomma americanum on dogs. Twelve purpose-bred beagles were
distributed into three groups of four dogs each; one group served as untreated
controls, and each of the other two groups received one of the test products.
Dogs were exposed to 25 adult ticks of each species for 10 minutes on
posttreatment days 3, 7, 14, 21, and 28. Unattached or repelled ticks were
collected and evaluated for viability, and on-dog tick counts were conducted at
3, 24, and 48 hours after tick exposure. The imidacloprid-permethrin formulation
provided significant repellency against I. scapularis for up to 3 weeks after
treatment, and both formulations provided good overall control of I. scapularis
and A. americanum during the study period.
PMID- 17039441
TI - Evaluation of an imidacloprid (8.8% w/w)--permethrin (44.0% w/w) topical spot-on
and a fipronil (9.8% w/w)--(S)-methoprene (8.8% w/w) topical spot-on to repel,
prevent attachment, and kill adult Rhipicephalus sanguineus and Dermacentor
variabilis ticks on dogs.
AB - This study evaluated the effectiveness of two topical spot-on formulations,
imidacloprid (8.8% w/w)--permethrin (44.0% w/w) and fipronil (9.8% w/w)--(S)
methoprene (8.8% w/w), to repel, prevent the attachment of, and kill adult
Rhipicephalus sanguineus and Dermacentor variabilis on dogs. Twelve purpose-bred
beagles were distributed into three groups of four dogs each; one group served as
untreated controls and each of the other two groups received one of the test
products. Dogs were exposed to 25 adult ticks of each species for 10 minutes on
posttreatment days 3, 7, 14, 21, and 28. Nonattached or repelled ticks were
collected and evaluated for viability, and on-dog tick counts were conducted at
3, 24, and 48 hours after tick exposure. The imidacloprid-permethrin formulation
provided significant repellency of R. sanguineus and D. variabilis for up to 3
and 4 weeks after treatment, respectively; and provided good overall control for
R. sanguineus and D. variabilis during the study period. The fipronil--(S)
methoprene formulation provided good overall tick control during the study
period.
PMID- 17039442
TI - Prevalence of Giardia in symptomatic dogs and cats throughout the United States
as determined by the IDEXX SNAP Giardia test.
AB - National prevalence of Giardia infection in dogs and cats presenting to clinics
with vomiting and/or diarrhea was examined using the IDEXX SNAP Giardia test kit.
Veterinary practices across the United States were sent an invitation to
participate in the survey and asked to use the test on fecal samples from the
target population. The survey requested that the clinics report the results of 20
or more tests. A total of 21,092 results were reported, comprised of 16,114 dogs
and 4,978 cats. Analysis of the data (excluding the handful of results reported
from Puerto Rico) showed a Giardia prevalence of 15.6% among dogs tested, and
10.8% among cats. This difference was statistically significant (p < 0.001).
Regional categorization into Northeast, Southeast, West, and Midwest drew out
significant (p < 0.001) differences in prevalence in most cases for dogs; the
differences were not significant for cats. These differences and other variables
are currently being examined with this and additional data sets. We conclude on
the basis of the SNAP test diagnostic that Giardia is a common enteric agent
among dogs and cats with gastrointestinal signs.
PMID- 17039443
TI - Comparison of sevoflurane and isoflurane in domestic ferrets (Mustela putorius
furo).
AB - Isoflurane anesthesia is commonly used in ferrets for routine examinations and
diagnostics. Sevoflurane is now being used as well, but there have been no
studies to date directly comparing these agents in domestic ferrets. A
prospective study was designed to evaluate the quality and speed of anesthetic
induction and recovery using isoflurane and sevoflurane in ferrets. In addition
effects on heart rate, blood pressure and packed cell volume were also recorded.
No significant differences were noted between anesthetic agents.
PMID- 17039444
TI - Three-year duration of immunity in cats following vaccination against feline
rhinotracheitis virus, feline calicivirus, and feline panleukopenia virus.
AB - Forty-two seronegative cats received an initial vaccination at 8 weeks of age and
a booster vaccination at 12 weeks. All cats were kept in strict isolation for 3
years after the second vaccination and then were challenged with feline
calicivirus (FCV) or sequentially challenged with feline rhinotracheitis virus
(FRV) followed by feline panleukopenia virus (FPV). For each viral challenge, a
separate group of 10 age-matched, nonvaccinated control cats was also challenged.
Vaccinated cats showed a statistically significant reduction in virulent FRV
associated clinical signs (P = .015), 100% protection against oral ulcerations
associated with FCV infection (P < .001), and 100% protection against disease
associated with virulent FPV challenge (P < .005). These results demonstrated
that the vaccine provided protection against virulent FRV, FCV, and FPV challenge
in cats 8 weeks of age or older for a minimum of 3 years following second
vaccination.
PMID- 17039445
TI - Three-year rabies duration of immunity in dogs following vaccination with a core
combination vaccine against canine distemper virus, canine adenovirus type-1,
canine parvovirus, and rabies virus.
AB - Thirty-two seronegative pups were vaccinated at 8 weeks of age with modified-live
canine distemper virus (CDV), canine adenovirus type-2 (CAV-2), and canine
parvovirus (CPV) vaccine and at 12 weeks with a modified-live CDV, CAV-2, CPV,
and killed rabies virus vaccine. An additional 31 seronegative pups served as age
matched, nonvaccinated controls. All test dogs were strictly isolated for 3 years
after receiving the second vaccination and then were challenged with virulent
rabies virus. Clinical signs of rabies were prevented in 28 (88%) of the 32
vaccinated dogs. In contrast, 97% (30 of 31) of the control dogs died of rabies
infection. These study results indicated that no immunogenic interference
occurred between the modified-live vaccine components and the killed rabies virus
component. Furthermore, these results indicated that the rabies component in the
test vaccine provided protection against virulent rabies challenge in dogs 12
weeks of age or older for a minimum of 3 years following vaccination.
PMID- 17039446
TI - Enrofloxacin use in a long-distance transport model of equine respiratory
disease.
AB - Successful clinical management of bacterial pneumonia in horses depends on the
administration of an appropriate antimicrobial agent at an adequate dosage and
frequency, given by the correct route of administration for an adequate duration.
Empiric antimicrobial therapy should be based on the clinician's experience and
current veterinary literature. Based on the frequency of Gram-positive bacterial
pathogens isolated from horses with bacterial pneumonia, every effort should be
made to provide antimicrobial coverage for this class of pathogens. Gram-negative
pathogens may co-exist; therefore, broad spectrum antimicrobial coverage may be
necessary. Antimicrobial agents posing potential drug related risks (e.g.
nephrotoxicity in dehydrated patients, peracute colitis in racehorses) may not be
appropriate for empiric use and enrofloxacin offers an enhanced spectrum of
antimicrobial activity with reduced risk of complication. Our findings indicate
that in cases of exclusive Gram-positive respiratory disease, solo therapy with
enrofloxacin is not indicated.
PMID- 17039447
TI - A comparison of N-butylscopolammonium and lidocaine for control of rectal
pressure in horses.
AB - In its FDA approved formulation, N-butylscopolammonium bromide (Buscopan
Injectable Solution, Boehringer Ingelheim Vetmedica) is an anticholinergic
spasmolytic agent indicated for management of abdominal pain associated with
spasmodic colic, flatulent colic, and simple impactions in horses. Use of this
drug ablates gastrointestinal peristalsis and rectal pressure. It ahs been
suggested that N-butylscopolammonium bromide could be used to facilitate rectal
examinations in horses. This study compared the effects of N-butylscopolammonium
bromide versus lidocaine and a saline control on rectal pressure and the number
of rectal strains during rectal examination. The results of this study indicate
that this drug increases the quality and, presumably, the safety of rectal
examinations in horses.
PMID- 17039448
TI - Evaluation of the efficacy provided by a Recombinant Canarypox-Vectored Equine
West Nile Virus vaccine against an experimental West Nile Virus intrathecal
challenge in horses.
AB - Efficacy of the Recombitek Equine West Nile Virus (WNV) vaccine was evaluated
against a WNV intrathecal challenge model that results in WNV-induced clinical
disease. Ten vaccinated (twice at days 0 and 35) and 10 control horses were
challenged 2 weeks after administration of the second vaccine with a virulent WNV
by intrathecal administration. After the challenge, eight of 10 controls
developed clinical signs of encephalomyelitis whereas one vaccinate exhibited
muscle fasciculation only once. Nine controls and one vaccinate developed a
fever. Histopathology revealed mild to moderate nonsuppurative encephalitis in
eight controls and one vaccinate. None of the vaccinates and all of the controls
developed WNV viremia after challenge. All vaccinated horses developed antibodies
to WNV after vaccination. These and results of previous studies demonstrate
efficacy of the Recombitek WNV vaccine against WNV-induced clinical disease and
natural challenge with WNV-infected mosquitoes.
PMID- 17039449
TI - An evaluation of the metaphylactic effect of ceftiofur crystalline free Acid in
feedlot calves.
AB - The relative effect of metaphylactic ceftiofur crystalline free acid (CCFA)
versus metaphylactic tilmicosin was evaluated in beef calves under commercial
feedlot conditions in Nebraska. At feedlot arrival, 11,605 animals at ultrahigh
risk of developing bovine respiratory disease (BRD) were allocated to one of
three experimental groups: CCFA-3 (6.6 mg/kg SC), CCFA-7 (6.6 mg/kg), or TILM-3
(tilmicosin, 10 mg/kg SC). Animals were eligible for subsequent BRD treatment 3
(CCFA-3 and TILM-3 groups) or 7 (CCFA-7 group) days later. Compared with the TILM
3 group, overall chronicity, overall mortality, BRD mortality, and metabolic
mortality rates were significantly (P < .05) lower in the CCFA-3 and CCFA-7
groups; average daily gain was significantly (P < .05) higher in the CCFA-3
group; the proportion of quality grade No Roll carcasses was significantly (P <
.05) lower in the CCFA-3 and CCFA-7 groups; and there were per-animal advantages
of 22.05 dollars and 18.98 dollars in the CCFA-3 and CCFA-7 groups, respectively.
In beef calves at ultrahigh risk of developing BRD, it is more cost effective to
administer metaphylactic CCFA than tilmicosin at feedlot arrival.
PMID- 17039450
TI - Evaluation of the efficacy of a modified-live combination vaccine against
abortion caused by virulent bovine herpesvirus type 1 in a one-year duration-of
immunity study.
AB - This study demonstrated that a multivalent vaccine containing modified-live
bovine herpesvirus type 1 (BHV-1) protected pregnant heifers and their fetuses
against virulent BHV-1 challenge exposure at 365 days after vaccination. The
percentage of abortions or fetal deaths caused by BHV-1 was significantly higher
in control heifers (10 of 10 [100.0%]) than BHV-1-vaccinated heifers (three of 19
[15.8%]).
PMID- 17039451
TI - Evaluation of the efficacy of a modified-live combination vaccine against bovine
viral diarrhea virus types 1 and 2 challenge exposures in a one-year duration-of
immunity fetal protection study.
AB - This study demonstrated that the modified-live bovine viral diarrhea virus (BVDV)
type 1 and 2 fractions of a multivalent vaccine protected pregnant heifers and
their fetuses against virulent BVDV types 1 and 2 challenge exposures at 370 days
after vaccination. All BVDV vaccinated heifers inoculated with either BVDV type 1
or 2 at approximately 62 to 94 days of gestation delivered fetuses or calves that
were negative for BVDV by ear-notch immunohistochemistry and virus isolation and
serum neutralization on a prenursing serum sample. In comparison, eight of nine
and 10 of 10 fetuses or calves from non-BVDV-vaccinated heifers were considered
persistently infected following exposure to BVDV type 1 and type 2, respectively.
PMID- 17039452
TI - Fetal protection following exposure to calves persistently infected with bovine
viral diarrhea virus type 2 sixteen months after primary vaccination of the dams.
AB - This study demonstrated that the bovine viral diarrhea virus (BVDV; types 1 and
2) fractions of a multivalent vaccine protected pregnant heifers and their
fetuses at 149 to 217 days of gestation against exposure to calves persistently
infected with BVDV type 2a. Eighty percent (eight of 10) of the control heifers
were viremic at least 1 day following challenge, whereas all (20 of 20) BVDV
vaccinated heifers were virus isolation-negative on all postchallenge assessment
days. Ninety percent (nine of 10) of the calves born to control heifers but only
5% (one of 20) of calves born to BVDV-vaccinated heifers seroconverted to BVDV
type 2 before ingesting colostrum. One calf born to a control heifer was
persistently infected. No calves from BVDV-vaccinated heifers were persistently
infected.
PMID- 17039454
TI - Efficacy of enrofloxacin against severe experimental Anaplasma marginale
infections in splenectomized calves.
AB - Four Anaplasma marginale-infected splenectomized calves with greater than 25%
parasitized erythrocytes received enrofloxacin at 12.5 mg/kg SC twice, 48 hours
apart. Two infected splenectomized calves were designated as untreated controls.
A precipitous decline in percent parasitized erythrocytes from 39.13% to less
than 1% was observed over 12 days following treatment. However, a self-limiting
recrudescence of A. marginale parasites was observed within 30 days after
treatment. Untreated control calves became moribund and were euthanized. These
data indicate that the regimen of enrofloxacin tested herein ameliorates, but
does not eliminate, A. marginale infections in splenectomized calves.
PMID- 17039453
TI - Use of a modified-live vaccine to prevent persistent testicular infection with
bovine viral diarrhea virus.
AB - A commercial vaccine containing modified-live bovine viral diarrhea virus (BVDV;
types 1 and 2) was administered to one group of 22 peripubertal bulls 28 days
before intranasal inoculation with a type 1 strain of BVDV. A second group of 23
peripubertal bulls did not receive the modified-live BVDV vaccine before
intranasal inoculation. Ten of 23 unvaccinated bulls--but none of the vaccinated
bulls--developed a persistent testicular infection as determined by
immunohistochemistry and polymerase chain reaction. Results of this study
indicate that administration of a modified-live vaccine containing BVDV can
prevent persistent testicular infection if peripubertal bulls are vaccinated
before viral exposure.
PMID- 17039455
TI - Induction of cell apoptosis in 3T3-L1 pre-adipocytes by flavonoids is associated
with their antioxidant activity.
AB - Obesity is biologically characterized at the cellular level by an increase in the
number and size of adipocytes differentiated from fibroblastic pre-adipocytes in
adipose tissue. In this study, we focused on the relationship between the
influence of flavonoids on cell population growth and their antioxidant activity.
The results showed that the inhibition of flavonoids (naringenin, rutin,
hesperidin, resveratrol, naringin and quercetin) on 3T3-L1 pre-adipocytes was
28.3, 8.1, 11.1, 33.2, 5.6 and 71.5%, respectively. In oxygen radical absorbance
capacity (ORAC) assay, quercetin had the highest ORAC(ROO) value among the six
flavonoids tested. Apoptosis assays showed that quercetin increased apoptotic
cells in time- and dose-dependent manner. Treatment of cells with quercetin
decreased the mitochondrial membrane potential in the courses of time and dose.
The cell apoptosis/necrosis assay showed that quercetin increased the number of
apoptotic cells, but not necrotic cells. Quercetin treatment of cells caused a
significant time- and dose-dependent increase in the caspase-3 activity. Western
analysis indicated that treatment of quercetin markedly down-regulated PARP and
Bcl-2 proteins, and activated caspase-3, Bax, and Bak proteins. These results
indicate that quercetin efficiently inhibits cell population growth and induction
of apoptosis in 3T3-L1 pre-adipocytes.
PMID- 17039456
TI - Visualization of astaxanthin localization in HT29 human colon adenocarcinoma
cells by combined confocal resonance Raman and fluorescence microspectroscopy.
AB - Astaxanthin, a carotenoid found in plants and seafood, exhibits
antiproliferative, antioxidant and anticarcinogenic properties. We show that
astaxanthin delivered with tetrahydrofuran is effectively taken up by cultured
colon adenocarcinoma cells and is localized mostly in the cytoplasm as detected
by confocal resonance Raman and broad-band fluorescence microspectroscopy image
analysis. Cells incubated with beta-carotene at the same concentration as
astaxanthin (10 microM) showed about a 50-fold lower cellular amount of beta
carotene, as detected by HPLC. No detectable Raman signal of beta-carotene was
found in cells, but a weak broad-band fluorescence signal of beta-carotene was
observed. beta-Carotene, like astaxanthin, was localized mostly in the cytoplasm.
The heterogeneity of astaxanthin and beta-carotene cellular distribution in cells
of intestinal origin suggests that the possible defense against reactive
molecules by carotenoids in these cells may also be heterogeneous.
PMID- 17039457
TI - Efficacy and food safety considerations of poultry competitive exclusion
products.
AB - Competitive exclusion (CE) products are anaerobic cultures of bacteria that are
applied to poultry hatchlings to establish a protective enteric microbiota that
excludes intestinal colonization by human food-borne pathogens. For safety of the
poultry flock and human consumers, the identities of bacteria in CE products need
to be known. A CE product is a culture of intestinal contents from adult
chickens. It may be microbiologically defined by analysis of bacteria isolated
from the culture, but many bacteria are hard to reliably isolate, identify, and
characterize with conventional techniques. Sequence analysis of 16S ribosomal RNA
(rRNA) genes may be more reliable than conventional techniques to identify CE
bacteria. Bacteria in CE products may contain antimicrobial drug resistance and
virulence mechanisms that could be transferred to the enteric bacteria of the
food animal and to the human consumer. Detection methods for specific
antimicrobial drug resistance and virulence genes and the integrase genes of
conjugative transposons, mostly utilizing PCR technology, are being developed
that can be applied to assess these risks in CE bacteria. With improvements in
efficacy, bacterial identification, and detection and control of the possible
risks of gene transfer, CE product technology can be made a more effective food
safety tool.
PMID- 17039458
TI - Total antioxidant capacity of spices, dried fruits, nuts, pulses, cereals and
sweets consumed in Italy assessed by three different in vitro assays.
AB - With the aim to expand the Italian total antioxidant capacity (TAC) database, the
TAC values of 11 spices, 5 dried fruits, 7 sweets, 18 cereal products, 5 pulses,
and 6 nuts were determined using three different assays and considering the
contribution of bound antioxidant compounds in fiber-rich foods (i. e. cereals,
legumes, and nuts). Among spices, saffron displayed the highest antioxidant
capacity, whereas among dried fruits, prune exhibited the highest value. The TAC
values of all the chocolates analyzed were far higher than the other sweet
extracts measured. Among cereal products, whole meal buckwheat and wheat bran had
the greatest TAC. Among pulses and nuts, broad bean, lentil and walnuts had the
highest antioxidant capacity, whereas chickpeas, pine nuts and peanuts were less
effective. The contribution of bound phytochemicals to the overall TAC was
relevant in cereals as well as in nuts and pulses. The complete TAC database
could be utilized to properly investigate the role of dietary antioxidants in
disease prevention.
PMID- 17039459
TI - Free radical scavenging and cytoprotective activities of phenolic antioxidants.
AB - The free radical scavenging activities of three flavonoids (quercetin, rutin and
catechin) and four hydroxycinnamic acids (caffeic, ferulic, sinapic, and
chlorogenic acids) were evaluated using both oxygen radical absorbance capacity
(ORAC) and lipid peroxidation inhibition capacity (LPIC) assays. The
cytoprotective effects of these compounds were also measured by the degree of
protection against H(2)O(2)-induced damage of human Jurkat cells. All compounds
exhibited protection against H(2)O(2)-mediated cytotoxicity in a dose-dependent
manner. The concentrations required to result in a 50% reduction in cell death
(EC(50) value) were calculated from their dose-response curves. These ranged from
0.15-2.65 microM. Overall, the four hydroxycinnamic acids tested were less
effective than the three flavonoids, and of all compounds tested, quercetin
offered the strongest protection against H(2)O(2)-induced cell death. A
comparison of the results showed that the ability to inhibit peroxidation of
lipids in a liposomal system (LPIC) correlated well with the cytoprotective
activities (EC(50)), but not with the ability to protect an aqueous fluorescent
substrate in the ORAC assays. The results suggest that the behavior of
antioxidants in a liposomal membrane is to some extent similar to the mechanism
involved in the protection of living cells from oxidative damage.
PMID- 17039460
TI - Human rectal mucosal gene expression after consumption of digestible and non
digestible carbohydrates.
AB - The effect of regular consumption of the low-digestible and prebiotic isomalt
versus the digestible sucrose on gene expression in rectal mucosa was examined in
a randomized double-blind crossover trial. Nineteen healthy volunteers received
30 g isomalt per day or 30 g sucrose as part of a controlled diet over two 4-week
test periods with a 4-week washout period in between. At the end of each test
phase rectal biopsies were obtained. After RNA extraction mucosal gene expression
was assayed using GeneChip microarrays. In addition, expression of cathelicidin
hCap18/LL37, cellular detoxification enzymes GSTpi, UGT1A1 and CYP3A4,
cyclooxygenase 2 and barrier factors MUC2 and ZO-1 were determined by real-time
RT-PCR. Microbiological analyses of fecal samples revealed a shift of the gut
flora towards an increase of bifidobacteria following consumption of the diet
containing isomalt. Isomalt consumption did not affect rectal mucosal gene
expression in microarray analyses as compared to sucrose. In addition, the
expression of cathelicidin LL37, GSTpi, UGT1A1, CYP3A4, COX-2, MUC2 and ZO-1 was
not changed in rectal biopsies. We conclude that gene expression of the human
rectal mucosa can reliably be measured in biopsy material taken at endoscopy.
Dietary intervention with the low digestible isomalt compared with the digestible
sucrose did not affect gene expression in the lining rectal mucosa.
PMID- 17039461
TI - Recent development of small molecular specific inhibitor of protein tyrosine
phosphatase 1B.
AB - Protein tyrosine phosphatases (PTPs), a large family of signaling enzymes, play
essential roles in intracellular signal transduction by regulating the cellular
level of tyrosine phosphorylation to control cell growth and differentiation,
metabolism, cell migration, gene transcription, ion-channel activity, immune
response, cell apoptosis, and bone development. Among all PTPs, protein tyrosine
phosphatase 1B (PTP1B) plays a seminal role in cellular signaling and in many
human diseases, including cancer, diabetes, and obesity. Therefore, small
molecular inhibitors of PTP1B can be promising drug candidates. Because of the
structural homologies in many families of PTPs, it is a challenging task to find
inhibitors specific to each PTP. Recent studies suggested that secondary binding
pockets or peripheral binding sites around the conserved active site should be
exploited to design novel potent and selective PTP1B inhibitors. In this review,
we discuss the structural and biological features of small molecular PTP1B
specific inhibitors, with particular emphasis on small molecular inhibitors
targeting PTP1B over the other PTPs that have been synthesized in the past 4
years.
PMID- 17039462
TI - Effect of urethral compliance on the steady state p-Q relationships assessed with
a mechanical analog of the male lower urinary tract.
AB - AIMS: Using a lumped parameter theoretical model of bladder outlet function, we
previously explored the relationship between the tube law of the urethra and the
pressure-flow characteristics during micturition [Mijailovich et al., 2004]. To
validate this theoretical model, we constructed a mechanical analog of the male
lower urinary tract that incorporated elements simulating all relevant parameters
of the theoretical model. In addition, we determined the effect of alterations in
compliance of the flow-controlling zone on these relationships. METHODS: In the
mechanical analog, the bladder neck and urethra were represented by a thin-walled
conduit made of latex rubber and the prostate with a fluid filled cuff of
variable compliance encircling the conduit. We measured in the same system steady
state pressure-flow (p-Q) and pressure-area (p-A) relationships of the flow
controlling zone. The effects of bladder outlet obstruction and prostatic
compliance on these relationships were simulated by varying cuff pressure and
capacitative coupling of the cuff, respectively. RESULTS: We demonstrated two
previously described flow regimes-critical for low Q, and subcritical for higher
Q. In the critical flow regime, the cross-sectional area of the collapsible
conduit downstream of the cuff became narrow up to a site where the area suddenly
expanded (elastic jump). Pressure losses across the cuff region decreased with
increasing Q as the elastic jump approached the cuff, and the jump vanished when
Q became subcritical. By altering prostatic cuff compliance and cuff pressure, we
showed that an increase in opening pressures was associated with a steeper p-Q
relationship. CONCLUSIONS: Using this mechanical analog, the measurements of p-A
and p-Q relationships under various experimental conduit conditions validated our
previous theoretical model of the male lower urinary tract. Both the experimental
measurements and our previous theoretical model predictions indicate that an
increase in opening pressure is associated with an increase in the slope of the p
Q relationship which becomes steeper with decreased cuff compliance. These data
are in accordance with urodynamic findings in patients with benign prostatic
hypertrophy (BPH) and suggest that a reduction in prostatic compliance
exacerbates the severity of obstruction.
PMID- 17039463
TI - Use of fetal magnetic resonance imaging in differentiating ileal atresia from
meconium ileus.
PMID- 17039464
TI - Lack of human muscle architectural adaptation after short-term strength training.
AB - The mechanisms governing the increases in force production in response to short
periods of strength training have yet to be fully elucidated. We examined whether
muscle architectural adaptation was a contributing factor. Ultrasound imaging
techniques were used to measure quadriceps muscle architecture at 17 sites in
vivo in trained and untrained legs of men and women after 2.5 and 5 weeks of
unilateral knee extension training, as well as in a nontraining control group.
Despite increases in knee extensor strength of the trained and untrained (women
only) legs, there were no changes in muscle thickness, fascicle angle, or
fascicle length in any of the muscles tested. The moderate correlation between
vastus lateralis thickness (middle site) and eccentric (r = 0.55; P < 0.05) and
concentric (r = 0.46; P < 0.1) torque after, but not before, training is
suggestive of neural rather than architectural adaptations predominating in the
early phase of training.
PMID- 17039465
TI - Development of novel poly(ethylene glycol)-based vehicles for gene delivery.
AB - The purpose of this research was to develop and characterize a gene delivery
vehicle with a poly(ethylene glycol) (PEG) backbone with the aim of overcoming
limitations, such as cytotoxicity and rapid clearance, associated with current
commonly used non-viral carriers. PEG was functionalized with DNA-binding
peptides (DBPs) to make a vehicle (DBP-PEG) capable of condensing DNA. Complexes
of plasmid DNA and DBP-PEG were formed and characterized by measuring particle
size, zeta potential, and transfection efficiency as a function of N:P charge
ratios (DBP-PEG amino groups:DNA phosphate). Dynamic light scattering showed that
DBP-PEG was able to condense DNA efficiently resulting in a population of
particles in the range of 250-300 nm. Neutral or slightly positive zeta
potentials were measured for charge ratios of 3.5:1 and greater. DBP-PEG/DNA
complexes, made with plasmids encoding the green fluorescent protein (GFP) and
beta-Galactosidase (beta-Gal) genes, were used to transfect Chinese hamster ovary
(CHO) cells. DBP-PEG/DNA was capable of transfecting cells and maximum
transfection efficiency was observed for N:P ratios from 4:1 to 5:1,
corresponding to zeta potentials from -4 to +1.6 mV. The effect of the DBP-PEG
vehicle on cell viability was assayed. DBP-PEG was associated with a higher
percentage of viable cells ( approximately 95%) than either polyethylenimine
(PEI) or poly-L-lysine (PLL), and with transfection efficiency greater than PLL,
but with somewhat lower than PEI. The results of this work demonstrate that PEG
can be used as the backbone for gene delivery vehicles.
PMID- 17039466
TI - Variation and causal factors of craniofacial robusticity in Patagonian hunter
gatherers from the late Holocene.
AB - Fueguian-Patagonian skulls have been characterized as some of the most robust of
any modern crania. However, the causal factors of such robusticity remain
unsettled. We assess within- and among-sample cranial robusticity of seven
samples from continental Patagonia and Tierra del Fuego, using geometric
morphometric techniques. In addition, the biomechanical, phylogenetic, and
climatic hypotheses proposed to account for robusticity in such samples are
discussed. Two Amerindian samples of farmers and two early middle Holocene
samples from South America were included. The results show: 1) large variation in
craniofacial robusticity among Patagonian samples, with the highest robusticity
in samples from south continental Patagonia and Isla Grande of Tierra del Fuego,
whereas central and north Patagonian samples display the same degree of
robusticity as farmer samples; 2) that early middle Holocene samples display
lower levels of robusticity than South Patagonian samples; and 3) strong
association between latitude and craniofacial robusticity, with the most robust
craniofacial morphologies occurring at the highest latitudes. In consequence,
neither masticatory stress nor retention of ancestral features is supported by
the morphological evidence analyzed. Hence it is hypothesized that endocrine
changes related to cold climate may be a plausible explanation for several
craniofacial features found in Fueguian and south continental Patagonian samples,
such as their large masticatory component, and pronounced supraorbital ridge and
glabellar region.
PMID- 17039467
TI - Male lifespan and the secondary sex ratio.
AB - Literature speculating on the fetal origins of later life morbidity often invokes
the "damaged cohort" theory, i.e., that maternal responses to exogenous shocks
induce "stress reactivity" in fetuses and thereby shorten the lifespan of males
in utero during stressful times. A rival, or "culled cohort," theory posits that
exogenous shocks to gravid females induce spontaneous abortions of frail male
fetuses, leaving relatively hardy survivors who enjoy, on average, lifespans
longer than males in less stressed birth cohorts. A recent test based on archival
data from Sweden supported the culled cohort theory. Several characteristics of
the Swedish data, however, raise questions regarding the external validity of the
findings. We repeat the test with data from Denmark, Iceland, and England and
Wales. We use time-series methods that control for trends, seasonal cycles, and
other forms of autocorrelation that could confound the test. None of the results
supports the "damaged cohort" theory. Consistent with the Swedish findings and
with evolutionary theory, we find support in Iceland and England and Wales for
the "culled cohort" theory. We discuss the implications of our findings for basic
research as well as for public health.
PMID- 17039468
TI - Menstrual cycle irregularities are associated with testosterone levels in healthy
premenopausal women.
AB - High androgen levels have been associated with menstrual irregularities in
clinical populations, but not in healthy women. We examined the association
between testosterone and menstrual irregularities in a nonclinical population of
194 healthy premenopausal women, none of whom reported chronic health conditions.
Women provided saliva samples for assay of salivary testosterone, and responded
to questions about length of menstrual cycles, variability in menses, and
retrospective history of menstrual irregularity. Results showed significant
correlations between testosterone and menstrual irregularities, even when women
with the most irregular cycles were excluded from analyses. This pattern was also
apparent for a subgroup of 27 women using hormonal contraceptives. Based on our
findings, it appears that even in healthy women reporting no health concerns,
menstrual irregularities are associated with higher levels of circulating
androgens.
PMID- 17039469
TI - A possible link between prenatal exposure to famine and breast cancer: a
preliminary study.
AB - In a study of 475 women born around the 1944-1945 Dutch famine, women exposed to
prenatal famine more often reported a history of breast cancer than nonexposed
women (hazard ratio, 2.6; 95% confidence interval, 0.9-7.7). They also had
alterations in reproductive risk factors. Prenatal famine may increase breast
cancer incidence.
PMID- 17039470
TI - Hair morphology and anthropological applications.
AB - The histological study of hair has a long history, dating from the 19th century.
We obtained a collection of hair taken from people of known geographic origin. We
analyzed these samples according to their transversal cut shape index, derived
from computerized image-processing. We noted statistically significant variation
according to the geographic origin of subjects. This morphological variation may
reflect genetic distance. This reliable, quick, and cheap technique could be used
in other existing anthropological material for which DNA analysis is usually
difficult.
PMID- 17039471
TI - Sex hormone-binding globulin and androgen levels in immigrant and British-born
premenopausal British Pakistani women: evidence of early life influences?
AB - In women, raised insulin levels are associated with low sex hormone-binding
globulin (SHBG) and high androgen levels, which are in turn linked to
infertility. Since insulin resistance and hyperinsulinemia are major health
problems for South Asians living in Western countries, we predicted that British
Pakistani women would have low SHBG and raised androgen levels compared to
European women. Given low birth weights in Pakistan, and known links between low
birth weight and insulin resistance in later life, we also predicted that
immigrant women born in Pakistan would have lower levels of SHBG and higher
levels of androgens than British-born British Pakistani women. We assessed SHBG,
testosterone, and the free androgen index (FAI) from a single serum sample taken
on days 9-11 of the menstrual cycle from 20-40-year-old women living in the UK:
30 immigrants from Pakistan, 30 British-born British Pakistani women, and 25
British-born women of European origin. Age-adjusted analyses showed no
significant differences in SHBG, testosterone, or FAI between British-born
Pakistani and European-origin women. However, immigrant British Pakistani women
had a significantly higher FAI than British-born British Pakistani women.
Adjustment for body mass index, waist-to-hip ratio, and smoking status did not
affect these results, but further adjustment for height, a marker of early
environment, reduced the P-value for the difference in FAI between immigrant and
British-born British Pakistani women to below significance. It is possible that
the poorer early environment of immigrant British Pakistani women was at least
partially responsible for their relatively high levels of free androgens.
PMID- 17039472
TI - Secondary sex ratio variation during stressful times: the impact of the French
revolutionary wars on a German parish (1787-1802).
AB - The observation that declines in the human secondary sex ratio (SSR) may be
linked to stressful periconceptional periods has received considerable attention
(Catalano [2003] Hum Reprod 18:1972-1975; Catalano et al. [2005] Int J Epidemiol
34:944-948, [2005] Hum Reprod 20:1221-1227, [2005] Paediatr Perinat Epidemiol
19:413-420). For the purpose of testing the external validity of this phenomenon,
birth records from four German village genealogies (N = 1,048) were analyzed to
study the impact of the French Revolutionary Wars (1787-1802) on the proportion
of male births. All births were subdivided into three cohorts (prewar, 1787-1792;
war, 1792-1797; and postwar, 1797-1802). Differences in SSR between cohorts
achieved statistical significance (chi2= 7.695; df = 2; P = 0.021). In addition,
changes in SSR before, during, and after the wars were monitored by risk
analysis. Using the SSR of the prewar period as a control, the results of the war
cohort failed to achieve statistical significance (regression coefficient,
0.257; ExpB= 0.773; P = 0.118), while the odds reduction of 32.3% in the postwar
period proved to be statistically significant (regression coefficient, -0.390;
ExpB= 0.677; P = 0.006). It is hypothesized that the experience of postwar
economic hardship (attributable to lowered food availability paired with dietary
changes) represents the most likely proximate cause. The study also finds
evidence of a parental sex ratio manipulation strategy meant to offset the female
biased SSR after the wars. It is argued that from an evolutionary perspective
both the decline in SSR in response to stress as well as parental manipulation of
the tertiary sex ratio convey reproductive advantages.
PMID- 17039473
TI - Measurement of leptin in dried blood spot samples.
AB - Leptin is important in a wide range of physiological processes, but logistical
constraints associated with venipuncture blood collection have limited research
on leptin in diverse, community-based settings. The aim of this short report is
to present and validate an enzyme immunoassay method for quantifying leptin in
samples of capillary whole blood collected from a simple finger prick and dried
on filter paper. The method was evaluated through analysis of precision,
reliability, stability, and comparisons with matched plasma and blood spot
samples. We report acceptable levels of assay precision and reliability, and good
agreement between results obtained from matched plasma and blood spot samples (r
= 0.976, P < 0.001). Leptin concentrations begin to deteriorate after only 3 days
at room temperature. Thus, care should be taken to refrigerate or freeze samples
promptly. The relative ease of blood spot sample collection may facilitate
research on leptin in a wider range of cultural and ecological settings.
PMID- 17039474
TI - High-sensitivity C-reactive protein, adiposity, and blood pressure in the Yakut
of Siberia.
AB - C-reactive protein (CRP), an acute-phase reactant and marker of inflammatory
response, is known to be an important predictor of future cardiovascular
mortality, independent of other risk factors. The purpose of this research was to
investigate the association between CRP, adiposity, and blood pressure in the
Yakut, an indigenous Siberian population undergoing rapid cultural change. We
conducted a cross-sectional study of 265 healthy Yakut adults in six villages in
rural northeastern Siberia. Plasma CRP was measured by high-sensitivity
immunoturbidimetric assay. The median CRP value was 0.85 mg/l, with values for
the 25th, 50th, and 75th percentiles of 0.30, 0.85, and 2.28 mg/l, respectively.
CRP was positively associated with age (r = 0.19; P = 0.002), but not plasma
lipids or smoking status. CRP was associated with measures of central adiposity
and characteristics of the metabolic syndrome, particularly in women. We found
significantly higher CRP across quintiles (Q) of waist circumference for women
(difference = 0.7 mg/l; P = 0.035), but not men (difference = 0.36 mg/l; P =
0.515). CRP was significantly associated with systolic blood pressure in men
(difference, Q1 vs. Q5 = 1.1 mg/l; P = 0.044) but not women (difference, Q1 vs.
Q5 = 0.03 mg/l; P = 0.713) after adjusting for age, waist circumference, and
smoking status. CRP in the Yakut was considerably lower than was reported for
other populations. The low CRP levels may be explained in part by a low
prevalence of abdominal obesity. Among the Yakut, the high physical-activity
demands of a traditional herding lifeway likely play a role through high energy
expenditure and maintenance of negative energy balance. Our findings underscore
the need for further research on the metabolic activity of adipose tissue, blood
pressure, and inflammatory activation in non-Western populations.
PMID- 17039475
TI - Digit ratio and hand-grip strength in German and Mizos men: cross-cultural
evidence for an organizing effect of prenatal testosterone on strength.
AB - The ratio of the length of the second and fourth digits (2D:4D), a putative proxy
of prenatal testosterone (PT), is correlated with measures of physical fitness.
The relationship between the organizing effect of PT on physical fitness is
likely to arise as a response to intrasexual male competition for females.
Physical strength is also likely to be important in intrasexual conflict, but
nothing is known concerning the relationship between 2D:4D and strength. The
strength of an individual is strongly influenced by body size, and 2D:4D is
strongly dependent on ethnicity. We present evidence that strength, as measured
from hand-grip strength, is related to 2D:4D in samples from two ethnic groups
(52 Caucasian men from Germany, and 88 Oriental Mizos men from northeast India)
which differed markedly in size. We found that 1) the German men were heavier and
stronger, but had higher 2D:4D (lower PT) than the Mizos men; 2) a median split
for grip strength into low (LGS) and high (HGS) groups showed that for right-hand
2D:4D (but not left-hand 2D:4D), the LGS men had higher 2D:4D than the HGS men;
and 3) the relationships between right 2D:4D and grip strength were independent
of ethnicity, age, height, and weight. Measures of grip strength correlate
strongly with strength in other muscle groups, so we conclude that PT may have an
early organizing effect on strength in men, and this is likely to be widespread
in human groups.
PMID- 17039476
TI - Use of serial ultrasound to identify periods of fetal growth restriction in
relation to neonatal anthropometry.
AB - The developmental origins of the health and disease hypothesis suggests that
fetal growth restriction (FGR) is a risk factor for several chronic diseases of
adulthood. However, most supporting studies use birth weight as a proxy measure
of FGR. To examine the relationship between birth weight and FGR, the present
study used serial prenatal ultrasound to identify periods of FGR during
gestation, and related these periods to birth size and shape. The data in this
study included serial prenatal ultrasounds performed on 1,349 high-risk
Scandinavian women enrolled in the National Institute of Child Health and Human
Development Study of Successive Small for Gestational Age Births. Fetal growth
velocity between ultrasounds was used to identify periods of isolated FGR, and
these were studied in relation to anthropometry at birth. FGR was identified in
184 subjects. A control group of 384 subjects without FGR was also identified.
Infants with first-trimester FGR (n = 20) had the highest birth weight, ponderal
index, and subscapular skinfold thickness. Infants with second-trimester FGR (n =
37) had the highest arm fat percentage. Infants with early third-trimester FGR (n
= 55) had the lowest mean birth weight and ponderal index. When infant gender,
gestational age, maternal body mass index, and smoking were controlled, birth
weight was predicted only by third-trimester FGR (not first- or second-trimester
FGR), and arm fat percent was predicted only by second-trimester FGR. These
results suggest that birth weight is not a valid indicator of FGR occurring
before the third trimester. Body composition may be a more sensitive marker of
early FGR.
PMID- 17039477
TI - Inbreeding from isonymy and repeated pairs of surnames in the Ebro Delta region
(Tarragona, Spain).
AB - The aim of the study was to evaluate the levels of inbreeding calculated from
isonymy with its random (Fr) and nonrandom (Fn) components, and repeated pairs of
surnames (RP2) and their random component (RP2r) in the Ebro River Delta region
(Tarragona, Spain). This region is made up of four parishes, and data correspond
to the period 1939-1995. The global results are on the same levels as observed in
other studies, but the values obtained in 3 of 4 parishes are relatively high.
The Fn global value is higher than Fr, as opposed to what happens in each parish,
so there is a clear Wahlund effect of subdivision of the region into parishes.
Among the parishes there is a clear differentiation for Amposta, with values much
lower than for the rest, due to the behavior of this population, i.e., a high
immigration rate.
PMID- 17039478
TI - Incorporating psychosocial health into biocultural models: preliminary findings
from Turkana women of Kenya.
AB - This paper investigates the potential benefits and limitations of including
psychosocial stress data in a biocultural framework of human adaptability.
Building on arguments within human biology on the importance of political
economic perspectives for examining patterns of biological variation, this paper
suggests that psychosocial perspectives may further refine our understanding of
the mechanisms through which social distress yields differences in health and
well-being. To assess a model that integrates psychosocial experiences, we
conducted a preliminary study among nomadic pastoralist women from northern
Kenya. We interviewed 45 women about current and past stressful experiences, and
collected anthropometric data and salivary cortisol measures. Focus group and key
informant interviews were conducted to refine our understanding of how the
Turkana discuss and experience distress. The results suggest that the most
sensitive indicators of Turkana women's psychosocial experiences were the
culturally defined idioms of distress, which showed high concordance with
measures of first-day salivary cortisol. Other differences in stress reactivity
were associated with the frequent movement of encampments, major herd losses, and
direct experiences of livestock raiding. Despite the preliminary nature of these
data, we believe that the results offer important lessons and insights into the
longer-term process of incorporating psychosocial models into human adaptability
studies.
PMID- 17039479
TI - Serum cobalt in children with essential hypertension.
AB - The effect of cobalt on the cardiovascular system is one of many aspects of
cobalt metabolism in humans. Elastin and collagen are the main proteins of the
vascular wall. The aims of this study were: 1) to determine serum cobalt
concentrations in children with hypertension; and 2) to study the correlation
between serum cobalt and some biological markers of the extracellular matrix of
the vascular wall, i.e., anti-elastin and anti-collagen type IV antibodies.
Patients showed statistically significant higher levels of systolic and diastolic
blood pressure, and significantly lower serum cobalt concentrations, than
controls. Children with hypertension showed significantly higher levels of total
cholesterol (P = 0.0003) and collagen type IV IgM (P = 0.04). Collagen type IV
IgG levels (P = 0.027) were lower than in controls. Serum cobalt in patients
showed a correlation with systolic blood pressure (r = -0.44, P = 0.05), elastin
IgM (r = 0.60, P = 0.007), and collagen type IV IgG (r = -0.46, P = 0.04). Our
data suggest the existence of a correlation between changes in levels of serum
cobalt, total cholesterol, anti-collagen type IV antibodies, and essential
hypertension in children. This is the first study of serum cobalt in children
with essential hypertension.
PMID- 17039480
TI - Prevalence of dopamine and 5HT2C receptor polymorphisms in Amerindians and in an
urban population from Argentina.
AB - We report on the frequency of DRD2A1, DRD3A1, DRD4/2R-10R, and 5HT2CA1 variants
in the population of the city of La Plata (Argentina) and in Amerindians from
Argentina, Paraguay, and Chile. In the Amerindian sample, the prevalence of
DRD2A1 and DRD4/4R variants were, respectively, significantly lower and
significantly higher than frequencies reported in other Native Americans.
Comparison of average allele and genotype frequencies between La Plata and
Amerindians showed significant differences for 5HT2CA1 and DRD4. As La Plata is a
population with predominant European and Amerindian components, we used mtDNA and
Y-specific markers to subdivide the La Plata sample into two strata: Amerindian
La Plata and non-Amerindian La Plata. Significant variations between the two
strata were detected for DRD2A1, DRD3A1, and DRD4/4R allele frequencies, and for
the homozygous DRD4/4R/4R genotype. Several controversial reports suggest a
possible association between a variant of DRD and/or 5HT2C receptor genes and the
clinical expression of several psychiatric disorders. We suggest that ethnic
variations in the prevalence of the allelic forms of these genes may be a
confounding factor to be taken into consideration in studies of association
between dopaminergic and serotonergic receptor genotypes and neuropsychiatric and
mood disorders.
PMID- 17039481
TI - Y-chromosome genetic variation in Rio de Janeiro population.
AB - The present-day Brazilian gene pool is known to be the outcome of an admixture
process of populations from different origins, mainly Amerindians, Europeans, and
Africans. It is also known that in Brazil, a wide variation in the admixture
process occurred in different regions of the country or even in different
subpopulations from the same region. In the present study, we aimed to
characterize the male lineages present in the Rio de Janeiro population, the
second most populated of the 26 Brazilian states. A random sample of 127
unrelated males from Rio de Janeiro was typed for 28 Y-chromosome-specific
biallelic markers. In total, 17 different haplogroups were defined within our
sample, most of them of European ancestry (88.1%). Those of sub-Saharan African
origin (E3a) amounted to 7.9%, while only 2 males carried Amerindian lineages
(characterized by the presence of an M3 mutation: haplogroup Q3). Using both Y
STR haplotype and Y-SNP haplogroup information, genetic distances were calculated
between the subgroup of Rio de Janeiro males carrying European haplogroups and
the Portuguese population. Low, nonsignificant, values were obtained. Thus, in
contrast with what is observed in their female counterparts, the vast majority of
the present Rio de Janeiro male gene pool is of European extraction, while the
original Amerindian lineages are residual and much less frequent than the sub
Saharan component resulting from the slave trade. These observations can be
interpreted as the signature of the strong gender asymmetry of the admixture
processes in colonial systems.
PMID- 17039482
TI - Height and weight of primary schoolchildren in Shiraz city, southern Iran, 2002.
AB - This paper aims at presenting updated growth reference data for height and weight
of 2,397 healthy schoolchildren (1,268 boys and 1,129 girls) aged 6.5-11.5 years
in Shiraz (Iran), using a multistage sampling scheme. Our schoolchildren are now
significantly taller and heavier for their age than their peers born 15 years
earlier. However, the statistical models for estimating age-related centiles were
consistent. A comparison of our current data with Centers for Disease Control
growth charts for 2000 show that our height and weight medians correspond almost
to the 40th centile of the latter, indicating less of a deficit than the previous
growth study in Shiraz. We conclude that it is more realistic to use local growth
standards for clinical work in Iran, which should be updated periodically.
PMID- 17039483
TI - Human skeletal muscle size and architecture: variability and interdependence.
AB - Seven hundred and eleven women and men (aged 3-94 years, including normal
individuals and highly trained bodybuilders) were tested for the thickness and
pennation angles of their triceps brachii (TB), vastus lateralis (VL), and
gastrocnemius medialis (GM) muscles. The variations of muscle thickness and
pennation angles were largest in TB (6-66 mm and 5-55 degrees), followed by VL (8
45 mm and 7-33 degrees) and GM (11-36 mm and 12-33 degrees), and women showed
smaller variations than men. These results suggest the existence of muscle- and
gender-specificity in the variability of muscle dimensions. Significant positive
correlations were observed between muscle thickness and pennation angles (r =
0.81, 0.61, and 0.56, for TB, VL, and GM, respectively), indicating that the size
dependence of the pennation angle is a general feature of pennate muscles.
PMID- 17039484
TI - Identification of the human/mouse syntenic common fragile site FRA7K/Fra12C1-
relation of FRA7K and other human common fragile sites on chromosome 7 to
evolutionary breakpoints.
AB - Common fragile sites (CFSs) are expressed as chromosome gaps in cells of
different species including human and mouse as a result of the inhibition of DNA
replication. They may serve as hot spots for DNA breakage in processes such as
tumorigenesis and chromosome evolution. Using multicolor fluorescence in situ
hybridization mapping, the authors describe here human CFS FRA7K on chromosome
band 7q31.1 and its murine homolog Fra12C1. Within the syntenic FRA7K/Fra12C1
region lies the IMMP2L/Immp2l gene with a size of 899/983 kb. The authors further
mapped 2 amplification breakpoints of the breast cancer cell line SKBR3 to the
CFSs FRA7G and FRA7H. The 5 molecularly defined CFSs on chromosome 7 do not
preferentially colocalize with synteny breaks between the human and mouse genomes
and with intragenomic duplications that have occurred during chromosome
evolution. In addition, in contrast to all currently reported data, CFSs in
chromosome band 7q31 do not show increased DNA helix flexibility in comparison
with control regions without CFS expression.
PMID- 17039485
TI - Difference in time course of modulation of synaptic transmission by group II
versus group III metabotropic glutamate receptors in region CA1 of the
hippocampus.
AB - We investigated the time course of modulation of synaptic transmission by group
II and group III metabotropic glutamate receptors in region CA1 of the
hippocampus. In the presence of 50 microM picrotoxin, pressure pulse application
of 1 mM glutamate resulted in a fast onset of suppression of synaptic
transmission in stratum lacunosum moleculare and a slower onset of suppression in
stratum radiatum, with both effects returning to baseline over the course of
several minutes. Application of 50 microM of the group II agonist (2R,4R)-APDC in
stratum lacunosum moleculare resulted in the same fast onset of suppression while
having no effect in stratum radiatum. Pressure pulse application of 100 microM DL
AP4 in stratum lacunosum moleculare and stratum radiatum resulted in a much
slower onset of suppression of synaptic transmission than (2R,4R)-APDC.
Suppression by (2R,4R)-APDC was accompanied by a rapid enhancement of paired
pulse facilitation, indicative of a presynaptic mechanism. This demonstrates that
activation of group II mGluRs in the hippocampus causes a fast onset of
suppression in stratum lacunosum moleculare, while activation of group III mGluRs
causes a slower onset of suppression. The difference in time course for group II
vs. group III mGluRs suggests a different functional role, with group II playing
a potential role in making synapses act as low pass filters.
PMID- 17039486
TI - Bidirectional redistribution of AMPA but not NMDA receptors after perforant path
simulation in the adult rat hippocampus in vivo.
AB - Long-term potentiation (LTP) in vitro reveals dynamic regulation of synaptic
glutamate receptors. AMPA receptors may be inserted into synapses to increase
neurotransmission, whereas NMDA receptors may redistribute within the synapse to
alter the probability of subsequent plasticity. To date, the only evidence for
these receptor dynamics in the hippocampus is from the studies of dissociated
neurons and hippocampal slices taken from young animals. Although synaptic
plasticity is induced easily, the extent of AMPA and NMDA receptor mobility after
LTP is unknown in the adult, intact hippocampus. To test whether AMPA or NMDAR
subunits undergo activity-dependent modifications in adult hippocampal synapses,
we induced LTP at perforant path-dentate gyrus (DG) synapses in anesthetized
adult rats, using high frequency stimulation (HFS), verified layer-specific Arc
induction, and analyzed the distribution of postsynaptic AMPA and NMDAR subunits,
using immunogold electron microscopy. The number of synapses with AMPA receptor
labeling increased with LTP-inducing HFS in the stimulated region of the dendrite
relative to the nonstimulated regions. The opposite trend was noted with low
frequency stimulation (LFS). Moreover, HFS increased and LFS decreased the ratio
of synaptic to extrasynaptic AMPA receptor labeling in the postsynaptic membrane.
In contrast, HFS did not significantly alter NMDAR labeling. Thus, LTP in the
adult hippocampus in vivo selectively enhanced AMPA but not NMDAR labeling
specifically in synapses undergoing activity-dependent plasticity relative to the
remainder of the dendritic tree. The results suggest a mechanism by which rapid
adjustments in synaptic strength can occur through localized AMPA receptor
mobility and that this process may be competitive across the dendritic tree.
PMID- 17039487
TI - Hippocampal contributions to recollection in retrograde and anterograde amnesia.
AB - Lesions restricted to the hippocampal formation and/or extended hippocampal
system (hippocampal formation, fornix, mammillary bodies, and anterior thalamic
nuclei) can disrupt conscious recollection in anterograde amnesia, while leaving
familiarity-based memory relatively intact. Familiarity may be supported by extra
hippocampal medial temporal lobe (MTL) structures. Within-task dissociations in
recognition memory best exemplify this distinction in anterograde amnesia. The
authors report for the first time comparable dissociations within recognition
memory in retrograde amnesia. An amnesic patient (A.D.) with bilateral fornix and
septal nuclei lesions failed to recognize details pertaining to personal past
events only when recollection was required, during recognition of episodic
details. His intact recognition of generic and semantic details pertaining to the
same events was ascribed to intact familiarity processes. Recollective processes
in the controls were reflected by asymmetrical Receiver's Operating
Characteristic curves, whereas the patient's Receiver's Operating Characteristic
was symmetrical, suggesting that his inferior recognition performance on episodic
details was reliant on familiarity processes. Anterograde and retrograde memories
were equally affected, with no temporal gradient for retrograde memories. By
comparison, another amnesic person (K.C.) with extensive MTL damage (involving
extra-hippocampal MTL structures in addition to hippocampal and fornix lesions)
had very poor recognition and no recollection of either episodic or
generic/semantic details. These data suggest that the extended hippocampal system
is required to support recollection for both anterograde and retrograde memories,
regardless of their age.
PMID- 17039488
TI - Incidence of bacteremias and invasive mycoses in children with high risk
neuroblastoma.
AB - BACKGROUND: Information on the incidence of infectious complications during for
treatment for high risk neuroblastoma (HR-NB) is limited. Bacteremias and
invasive mycoses may be considered surrogate markers of the infection burden.
PATIENTS AND METHODS: Data on bacteremias and invasive mycoses occurring during 3
consecutive protocols for front line (NB-89; NB-92; NB-97) or salvage therapy
(TVD) for HR-NB were reviewed. The cumulative risk of developing a first episode
and the rate of infections during the entire length of each protocol were
evaluated. RESULTS: Front line protocols were given to 80 patients for a total of
22,070 days at risk; salvage treatment was given to 24 children for 2,909 days at
risk. During front line therapy 41 infectious episodes were diagnosed in 29 (36%)
patients, for a 45% cumulative risk and an infection rate (IR) of 0.19/100
patient-days-at risk. Salvage therapy determined five infectious episodes in four
(17%) patients, with a 39% cumulative risk, and an IR of 0.17. The IR during the
phase of high dose chemotherapy with hematopoietic stem cell rescue (megatherapy)
included in the three front line protocols decreased over time (1.54 in NB-89;
0.52 in NB-92 and 0.0 in NB 97; P = 0.001), possibly because of the use of less
aggressive conditioning regimens, without radiotherapy. CONCLUSIONS: The IRs of
protocols for HR-NB did not change over time. The megatherapy-related phases are
those at highest risk.
PMID- 17039489
TI - Respiratory symptoms in a boy revealing Carney triad.
AB - The association of gastrointestinal stromal cell tumor (GIST), paraganglioma, and
pulmonary chondroma is known as the Carney triad, occurring predominantly in
young adult females. We present the case of a 14-year-old male with respiratory
symptoms resulting in the diagnosis Carney triad.
PMID- 17039490
TI - Diffusion of nutrients molecules and model drug carriers through mucin layer
investigated by magnetic resonance imaging with chemical shift resolution.
AB - Magnetic resonance imaging (MRI) with chemical shift resolution is a recent
extension of MRI and it provides information about species resolved molecular
transport on the macroscopic scale in complex systems. In this contribution, we
show that by using this novel method, one can predict the behavior of drug and
food molecules when they are in contact with the mucosal layer in the
gastrointestinal tract. For the first time, the transport properties of a mixture
of nutrients (i.e., a solution of ethanol and glucose) and of a model drug
carrier (i.e., an equimolar solution of cationic and nonionic surfactants)
through a mucin gel have been investigated. This study shows that transport
properties of the diffusing molecules through a mucin gel are dependent on their
size and physicochemical properties. In addition, we show that mucin gel acts as
an efficient selective barrier. It favors the disintegration of mixed micelles of
nonionic and cationic surfactants by stopping the diffusion of cationic
surfactants with slightly affecting the diffusion of the nonionic surfactants.
PMID- 17039491
TI - Nodal downstaging predicts survival following induction chemotherapy for stage
IIIA (N2) non-small cell lung cancer in CALGB protocol #8935.
AB - BACKGROUND AND OBJECTIVES: CALGB 8935 was a phase II protocol for
mediastinoscopically staged IIIA (N2) non-small cell lung cancer. Induction
cisplatin/vinblastine chemotherapy was followed by surgical resection, adjuvant
cisplatin/vinblastine, and radiotherapy. We now evaluate the prognosis of
pathologic nodes. METHODS: Failure-free survival was calculated from a landmark 3
months after resection to account for heterogeneity in adjuvant therapy. RESULTS:
Nine of 42 (21%) resected patients had no residual N2 disease. This subset of 9
had a median failure-free interval of 47.8 months from landmark, whereas the 33
patients (79%) with persistent N2 disease had a median failure-free survival of
8.2 months from landmark (P=0.01). Although 21/42 (50%) had an incomplete
resection (positive highest resected node and/or margin), completeness of
resection did not influence failure-free survival. There were 3 distant and no
local recurrences among the N2 negative group, and 12 local recurrences among
patients with residual N2 disease (P=0.041). CONCLUSIONS: These data suggest: (1)
persistent N2 disease following induction chemotherapy is unfavorable; (2)
patients downstaged to N2 negative may benefit from surgical resection; however,
(3) 33% of N2 negative patients suffered disease relapse.
PMID- 17039492
TI - Consideration of serum glucose levels during malignant mediastinal lymph node
detection in non-small-cell lung cancer by FDG-PET.
AB - BACKGROUND AND OBJECTIVE: Glucose and FDG compete for uptake by cancers. Here, we
undertook to improve diagnostic accuracy of FDG-PET for determining mediastinal
lymph node (LN) status in NSCLC by considering serum glucose level. METHODS:
NSCLC patients (n = 70) who underwent curative lung resection and mediastinal LN
dissection within 1 month of FDG-PET were enrolled. MaxSUV was calculated using
lean body weight and used to determine a new parameter (maxSUV x serum glucose
level; maxSUV-GL). Histopathologic LN results were compared with maxSUV and
maxSUV-GL values. RESULTS: Of 71 LN stations whose FDG uptake could be measured,
21 were malignant and 50 benign. MaxSUV of LN had AUC of 0.729 (95% CI: 0.610
0.827) by ROC analysis with sensitivity of 47.6% (10/21), specificity of 94.0%
(47/50), and a cutoff value of 3.3. Using maxSUV-GL the corresponding values
were; AUC 0.825 (95% CI: 0.716-0.905) and sensitivity 76.2% (16/21), with a
cutoff value of 290.4, which represented a significant improvement (P < 0.01)
without compromising specificity 88.0% (44/50) (P > 0.05). The exclusion of neo
adjuvant chemotherapeutic and diabetic patients resulted in a similar improvement
in diagnostic accuracy. CONCLUSION: By considering serum glucose level during FDG
PET using the new parameter maxSUV-GL, sensitivity for malignant mediastinal LN
detection is improved.
PMID- 17039493
TI - Theoretical study of interactions between muscle aldolase and F-actin: insight
into different species.
AB - Interactions of the glycolytic enzyme, fructose-1,6-bisphosphate aldolase
(aldolase), with F-actin may be one mechanism for the colocalization of
glycolytic enzymes. Examination of these interactions in different animal species
tests this hypothesis by observing whether binding sites are conserved across
species. Brownian dynamics (BD) simulations provide descriptions of such protein
protein interactions with the muscle isoforms of zebra fish and human aldolase.
The results are compared with previous results obtained for rabbit muscle and
yeast. The aldolase binding groove previously determined in rabbit muscle is
conserved in both the human and fish muscle isoforms. The nonspecific radial free
energies of interaction are similar with fish being slightly weaker than human
and rabbit: human, -2.27 +/- 0.05 kcal/mol; rabbit, -2.0 +/- 0.04 kcal/mol; and
fish, -1.5 +/- 0.03 kcal/mol. BD results show a large Boltzmann population of
complexes formed around the A/D and B/C grooves of aldolase with the most
feasible binding mode comprising two aldolase subunits to subdomain I region of
the actin subunits. These results show that the location of the important
residues and binding site for fish and human aldolase is very similar to that in
rabbit and that in different animals the binding site is conserved. This suggests
that the binding interaction between aldolase and F-actin is general in animal
muscles and is rendered possible and energetically favorable through the
conservation of this binding site.
PMID- 17039494
TI - Biowaiver monographs for immediate release solid oral dosage forms: prednisolone.
AB - Literature data relevant to the decision to allow a waiver of in vivo
bioequivalence (BE) testing for the approval of immediate release (IR) solid oral
dosage forms containing prednisolone are reviewed. Data on its solubility, oral
absorption, and permeability are not totally conclusive, but strongly suggest a
BCS Class 1 classification. Prednisolone's therapeutic indications and
therapeutic index, pharmacokinetics, and the possibility of excipient
interactions were also taken into consideration. Available evidence indicates
that a biowaiver for IR solid oral dosage forms formulated with the excipients
tabulated in this article would be unlikely to expose patients to undue risks.
PMID- 17039495
TI - Densin is a novel cell membrane protein of Sertoli cells in the testis.
AB - Cell-cell interactions between Sertoli cells and germ cells are crucial for the
maturation of germ cells in spermatogenesis but the structural and functional
aspects of the interactions remain to be fully elucidated. Densin is a junction
protein suggested to play a role in establishment of specific cell-cell contacts
in the post-synaptic densities of the brain and the slit diaphragm of the kidney
podocyte. In the present study, densin was discovered to be expressed in the
testis of the man and the mouse. Expression of densin at the gene and the protein
level was studied by using RT-PCR and Western blotting analyses, and the
localization of densin was explored with immunofluorescence staining. RT-PCR and
Western blotting analyses showed that densin is expressed at the gene and the
protein levels. Immunofluorescence staining localized the expression of densin to
the cell membranes of Sertoli cells suggesting that densin may be an adherens
junction protein between Sertoli cells and developing germ cells. Densin is a
novel testicular protein expressed in the cell membranes of Sertoli cells. Its
functional role remains to be assessed.
PMID- 17039496
TI - The risk of secondary malignancies over 30 years after the treatment of non
Hodgkin lymphoma.
PMID- 17039498
TI - Cancer-specific mortality after radiation therapy with short-course hormonal
therapy or radical prostatectomy in men with localized, intermediate-risk to high
risk prostate cancer.
AB - BACKGROUND: The presence of multiple determinants of aggressive cancer biology
may impact prostate cancer-specific mortality (PCSM) rates compared with fewer
factors. The authors estimated PCSM after radiation therapy with short-course
androgen suppression therapy (RT+AST) or radical prostatectomy (RP) in men with
clinically localized, intermediate-risk to high-risk prostate cancer. METHODS:
The study cohort included 3240 men treated from 1981 to 2002 with RT with 6
months of AST (n = 550) or RP (n = 2690) for localized prostate cancer with at
least 1 risk factor (prostate-specific antigen [PSA] >10 ng/mL, biopsy Gleason
score 7-10, or clinical tumor category T2b or T2c). Competing risks regression
analyses were used to determine whether the number of risk factors present was
associated with time to PCSM. RESULTS: Men with all 3 risk factors had
significantly shorter time to PCSM after RT+AST (adjusted hazards ratio [HR] of
9.3; 95% confidence interval [95% CI], 1.9-44.5 [P(Gray) = .005]) or RP (adjusted
HR of 6.3; 95% CI, 3.2-12.2 [P(Gray) < .001]) when compared with men with any 1
or 2 risk factors. The 7-year estimates of PCSM for men having 1, 2, or 3 risk
factors were 0.83% (95% CI, 0.27-1.4%), 2.6% (95% CI, 1.0-4.2%), and 12.6% (95%
CI, 7.1-18.1%), respectively. CONCLUSIONS: Men with multiple determinants of
intermediate-risk to high-risk prostate cancer have significantly increased
estimates of PCSM despite aggressive therapy compared with men with only 1 or 2
determinants. These men are appropriate candidates for enrollment onto randomized
controlled trials evaluating the benefit of adding systemic therapies such as
docetaxel to RT+AST or RP.
PMID- 17039499
TI - Quality measures for the use of adjuvant chemotherapy and radiation therapy in
patients with colorectal cancer: a systematic review.
AB - BACKGROUND: Chemotherapy (CT) and radiation therapy (RT) are essential components
of adjuvant (preoperative or postoperative) therapy for many patients with
colorectal cancer (CRC); however, quality measures (QMs) of these critical
aspects of CRC treatment have not been characterized well. Therefore, the authors
conducted a systematic review of the literature to determine the available QMs
for adjuvant CT and RT in patients with CRC and rated their usefulness for
assessing the delivery of quality care. METHODS: The MEDLINE and Cochrane data
bases were searched for all publications that contained potential/actual QMs
pertaining to adjuvant therapy for CRC. Identified QMs were rated by using
criteria developed by the National Quality Forum. RESULTS: Thirty-two articles
met the established inclusion/exclusion criteria. Those 32 articles contained 12
potential or actual QMs, 6 of which had major flaws that limited their
applicability. The most useful QMs identified were 1) the percentage of patients
with AJCC Stage III colon cancer who received postoperative CT and 2) the
percentage of patients with Stage II or III rectal cancer who received
chemoradiotherapy. CONCLUSIONS: To the authors' knowledge, very few QMs
pertaining to adjuvant CT or RT for CRC have been published to date, and only
half of those measures were rated as useful, acceptable, and valid in the current
literature review. Future research should focus on refining existing QMs and on
developing new QMs that target important leverage points with respect to the
provision of adjuvant therapy for patients with CRC.
PMID- 17039500
TI - Neoplastic stem cells: a novel therapeutic target in clinical oncology.
AB - Cancer is among the leading causes of morbidity and mortality in the Western
world. Despite recent advances, most therapeutic approaches fail to eradicate the
entire neoplastic clone. The remaining cells often develop metastasis and/or
recurrences and therefore may represent attractive targets of therapy. A new
exciting concept in this regard suggests that each neoplasm represents a
heterogeneous population of cells that pertain to long-term tumor growth both in
vivo in the natural host and in experimental animals. This concept postulates the
existence of small fractions of 'tumor stem cells' that exhibit a capacity for
self-renewal and unlimited growth and therefore are distinct from their progeny.
Based on these hypotheses, the targeting of neoplastic stem cells is considered
indispensable for eradication of the entire clone and for the development of
curative treatment approaches. However, tumor stem cells often may be quiescent
cells and may express a different profile of targets compared with 'more mature'
tumor cells. Therefore, current efforts have attempted to characterize target
expression profiles in cancer stem cells in various malignancies. In the this
review, the authors have provided a brief summary of the current knowledge of
neoplastic stem cells and the application of respective concepts in translational
oncology with the ultimate objective of improving anticancer therapy.
PMID- 17039501
TI - Is intraoperative touch imprint cytology of sentinel lymph nodes in patients with
breast cancer cost effective?
AB - BACKGROUND: Sentinel lymph nodes (SLNs) are generally evaluated postoperatively,
requiring 5-7 days for assessment. SLNs can also be evaluated intraoperatively by
using touch imprint cytology (TIC), thus providing the surgeon immediate feedback
and allowing for concurrent completion node dissection (CND) for positive SLNs.
The authors hypothesized that TIC, when compared with standard postoperative SLN
assessment alone, would permit a cost-effective evaluation of SLNs in patients
with clinically node-negative breast cancer. METHODS: A decision-analysis model
was created to compare TIC with standard postoperative SLN assessment alone.
Sensitivity and specificity of TIC were determined prospectively from 342
patients who underwent SLN biopsy assessed by both techniques. Short-term health
states associated with surgical staging were defined, and utilities were
estimated using EuroQol-5D. Base-case analysis was performed to estimate quality
adjusted life years and the incremental cost-effectiveness ratio. Sensitivity
analyses were performed to examine stability of model parameters. RESULTS: For
each tumor stage, TIC was cost effective, and for patients with larger tumors (T3
and T4), TIC was the dominant strategy. The analysis was robust to changes in
sensitivity and specificity of TIC, prevalence of metastasis, probability of
complications, and cost. However, when utility associated with standard SLN
assessment was 0.9 or greater, this became the preferred strategy. CONCLUSIONS:
TIC is cost effective for assessing SLN metastasis intraoperatively. For patients
with larger tumors, it is not only more effective, but also less costly than
standard SLN assessment alone. TIC may be particularly useful for patients who
experience significant anxiety while awaiting results of standard SLN assessment.
PMID- 17039502
TI - Molecularly targeted therapy for melanoma: current reality and future options.
AB - Effective therapy for melanoma remains an unmet goal, with most traditional
therapies representing inadequate trade-offs among the several goals of
specificity, efficacy, and toxicity. Targeted molecular therapeutics are tailored
to genetic abnormalities that are associated with tumor progression. Modulation
of aberrant signaling pathways in cancer cells has the potential to provide more
effective and potentially nontoxic therapy for a broad range of cancers,
including melanoma. Among the possible targets in melanoma are the Ras-MAPK and
PI3K/AKT signal transduction pathways, the proteasome, histone deacetylases,
methyltransferases, and melanoma-induced angiogenesis.
PMID- 17039505
TI - Randomized trial versus registry data--comparing apples and ORCHIDs.
PMID- 17039503
TI - Multiinstitutional validation of the UCSF cancer of the prostate risk assessment
for prediction of recurrence after radical prostatectomy.
AB - BACKGROUND: The University of California, San Francisco (UCSF) Cancer of the
Prostate Risk Assessment (CAPRA) is a novel preoperative index which predicts the
risk of biochemical recurrence after radical prostatectomy. The performance of
the index is at least as good as the best available instruments based on clinical
variables, and the 0 to 10 score is simple to calculate for both clinical and
research purposes. This study used a large external dataset to validate CAPRA.
METHODS: Data were abstracted from the Shared Equal Access Regional Cancer
Hospital (SEARCH) database, a registry of men who underwent radical prostatectomy
at 4 Veterans Affairs and 1 active military medical center. Of 2096 men in the
database, 1346 (64%) had full data available to calculate the CAPRA score.
Performance of the CAPRA score was assessed with proportional hazards regression,
survival analysis, and the concordance (c) index. RESULTS: Of the studied
patients, 41% were non-Caucasian, and their mean age was 62 years. Twenty-six
percent suffered recurrence; median follow-up among patients who did not recur
was 34 months. The hazard ratio (HR) for each 1-point increase in CAPRA was 1.39
(95% CI [confidence interval], 1.31-1.46). The 5-year recurrence-free survival
rate ranged from 86% for CAPRA 0-1 patients to 21% for CAPRA 7-10 patients.
Increasing CAPRA scores were significantly associated with increasing risk of
adverse pathologic outcomes. The c-index for CAPRA for the validation set was
0.68, compared with 0.66 for the original development set. CONCLUSIONS: The UCSF
CAPRA accurately predicted both biochemical and pathologic outcomes after radical
prostatectomy among a large, diverse, cohort of men. These results validated the
effectiveness of this powerful and straightforward instrument.
PMID- 17039506
TI - Effect of cytoplast on the development of inter-subspecies nuclear transfer
reconstructed goat embryo.
AB - The aim of this study was to investigate effect of cytoplast on the development
competence of reconstructed embryos derived from inter-subspecies somatic cell
nucleus transfer (SCNT). First, the development potency of reconstructed embryos
produced by transferring Boer goat fibroblast cell nucleus of different ages into
enucleated Sannen goat ova was evaluated in order to determine which age of
nuclear donor is favorable for the reconstructed embryos development. Secondly,
the another component of reconstructed embryos, "cytoplast," was evaluated by
comparing the effect of ovum cytoplast derived from Sannen male symbol x Boer
female symbol descendant on the reconstructed embryos development to that of
Sannen goat ovum cytoplast. The results revealed that the development rate of the
reconstructed embryos derived from 2 months old Boer goat somatic cells was the
highest, their gestation rate was up to 50%, and one viable male offspring was
obtained. The cytoplast derived from the crossbreeding goats improves the
development competence of reconstructed embryos, which birth rate was 5.5%. The
genetic identification of offspring by using PCR-SSCP analysis confirmed that
these cloned kids were derived from the donor. The results above reveal that the
cytoplast of Sannen goat ovum could induce the dedifferentiation of somatic cell
nuclei derived from Boer goat, but the reprogramming process of these
reconstructed embryos seems incomplete, probably due to some incorrect processes
happened after implantation. Relatedness components of nucleus donor in cytoplast
of the crossbreeding goat may be helpful to induce the dedifferentiation of
somatic cell nuclei completely and improve the development competence of the
reconstructed embryos.
PMID- 17039507
TI - Monte Carlo sampling of near-native structures of proteins with applications.
AB - Since a protein's dynamic fluctuation inside cells affects the protein's
biological properties, we present a novel method to study the ensemble of near
native structures (NNS) of proteins, namely, the conformations that are very
similar to the experimentally determined native structure. We show that this
method enables us to (i) quantify the difficulty of predicting a protein's
structure, (ii) choose appropriate simplified representations of protein
structures, and (iii) assess the effectiveness of knowledge-based potential
functions. We found that well-designed simple representations of protein
structures are likely as accurate as those more complex ones for certain
potential functions. We also found that the widely used contact potential
functions stabilize NNS poorly, whereas potential functions incorporating local
structure information significantly increase the stability of NNS.
PMID- 17039508
TI - The StarClose Vascular Closure System: interventional results from the CLIP
study.
AB - BACKGROUND: The StarClose Vascular Closure System is a femoral access site
closure technology that uses a flexible nitinol clip to complete a
circumferential, extravascular arteriotomy close. The Clip CLosure In
Percutaneous Procedures study was initiated to study the safety and efficacy of
the StarClose device in subjects undergoing diagnostic and interventional
catheterization procedures. METHODS: A total of 17 U.S. sites enrolled 596
subjects, with 483 subjects randomized at a 2:1 ratio to receive StarClose or
standard compression of the arteriotomy after the percutaneous procedure. The
study included roll-in (n = 113), diagnostic (n = 208), and interventional (n =
275) arms with a primary safety endpoint of major vascular complications through
30 days and a primary efficacy endpoint of postprocedure time to hemostasis.
RESULTS: The results of the diagnostic StarClose cohort have been reported
separately. Results for the interventional arm revealed major vascular
complications occurring in 1.1% of StarClose subjects (2/184) and 1.1% in manual
compression subjects (1/91; P = 1.00). No infections were seen in either cohort.
Minor complications in the StarClose interventional group occurred at a rate of
4.3% (8/184) and with compression at 9.9% (9/91; P = 0.107). Pseudoaneurysm or
arteriovenous fistula was not seen with StarClose. With StarClose, procedural
success was 100% (136/136) for the diagnostic group and 98.9% (181/183) in the
interventional group. Device success for the treatment group was 86.8%. In the
interventional cohort, 87.3% (158/181) of StarClose subjects reported a pain
scale of 0-3 compared with 93.3% (84/90) in the compression group, which was not
statistically different. CONCLUSIONS: The clinical results of this study
demonstrate that the StarClose Vascular Closure System is noninferior to manual
compression with respect to the primary safety endpoint of major vascular events
in subjects who undergo percutaneous interventional procedures. StarClose
significantly reduced time to hemostasis, ambulation, and dischargeability when
compared with compression.
PMID- 17039509
TI - The safety and efficacy of the StarClose Vascular Closure System: the ultrasound
substudy of the CLIP study.
AB - BACKGROUND: The StarClose Vascular Closure System (Abbott Vascular, Redwood City,
CA) features a nitinol clip that is designed to achieve closure of the femoral
arteriotomy access site. The CLIP Study was performed to assess the safety and
efficacy of StarClose when compared with standard manual compression following 5
6 French diagnostic or interventional percutaneous procedures. A substudy of this
trial was designed to assess the utility of duplex ultrasonography to assess
patency of the femoral artery and to determine access site complications
(pseudoaneurysm, arteriovenous fistula, hematoma, deep vein thrombosis) in a
multicenter prospective trial. This is the report of the duplex ultrasound (DUS)
substudy of the CLIP trial. METHODS: A total of 17 U.S. sites enrolled 596
subjects with 483 subjects randomized at a 2:1 ratio to receive StarClose or
manual compression of the arteriotomy after a percutaneous procedure. The study
included roll-in (n = 113), diagnostic (n = 208), and interventional (n = 275)
arms with a primary safety endpoint of major vascular complications through 30
days and a primary efficacy endpoint of postprocedure time to hemostasis. A
substudy of the CLIP interventional arm evaluated DUS images of the closure site
at five study sites, targeting 100 subjects at day 30 following hemostasis. The
DUS protocol was devised and implemented by an independent vascular ultrasound
core laboratory with extensive experience in vascular device trials. DUS inguinal
region from 6 cm proximal to 6 cm distal to the arteriotomy puncture was
performed. A qualitative examination was performed to determine the presence of
iatrogenic vascular injuries: hematoma, pseudoaneurysm (PSA), arteriovenous
fistula (AVF), and arterial/venous thrombosis or stenosis using 2-dimensional
gray scale, color, and focused Doppler images. RESULTS: DUS of 96 subjects
randomized to StarClose (n = 71) and compression (n = 25) were performed and
evaluated. There was no evidence of hematoma, PSA, or AVF observed in the
StarClose group. No StarClose subjects in the substudy had a PSA or AVF. All
patients in the substudy demonstrated patency of the access site artery and vein
without thrombosis or stenosis. Finally, in the entire study cohort, no
clinically-driven DUS studies demonstrated iatrogenic vascular injury or vessel
thrombosis in the StarClose treated patients. CONCLUSION: DUS, a safe and
reliable method for determining the safety and efficacy of access site closure
devices, is a reliable, safe, inexpensive and accurate method of assessing
vascular access site complications in multicenter trials. In this substudy of the
CLIP study, DUS found no statistical difference in access site complications
between the StarClose and manual compression groups. Both groups maintained
vessel patency without stenosis, thrombosis, hematoma, pseudoaneurysm, or AV
fistula.
PMID- 17039510
TI - Sustained increased risk of adverse cardiac events over 5 years after
implantation of gold-coated coronary stents.
AB - OBJECTIVE: To study the 5-year outcome of patients treated with gold-coated stent
placement. BACKGROUND: We have previously shown in the setting of a randomized
trial that gold-coated stents are associated with worse mid-term outcome, mainly
because of an increased risk of restenosis, compared to uncoated stents. The long
term outcome and, in particular, mortality risk after implantation of gold-coated
stents are not known. METHODS: A total of 731 patients with symptoms or signs of
ischemia received randomly either a gold-coated (n = 367) or an uncoated steel
stent (n = 364) of identical design. Patients were clinically followed-up at 1
and 5 years. The primary endpoint of the study was the composite of major cardiac
events (death, myocardial infarction, or target vessel revascularization (TVR)).
The incidence of death was a secondary endpoint. RESULTS: Five-year follow-up was
available in 97.5% of the patients. The composite of death, myocardial
infarction, or TVR occurred in 51% of the patients treated with gold-coated
stents and 40% of the patients treated with uncoated stents (P = 0.005). Of note,
there was a marked increase in the absolute difference in mortality between
patients in the gold-coated and uncoated stent groups, from 1.6% at 1 year to
4.9% after 5-year follow-up (P = 0.09). A multivariate analysis showed that gold
coated stent implantation was independently associated with 5-year mortality
(hazard ratio, 1.46; 95% confidence interval, 1.02-2.09; P = 0.04). CONCLUSIONS:
Gold-coated stents are associated with a sustained increased overall risk for
major cardiac events, and notably, they may increase the long-term mortality
risk.
PMID- 17039511
TI - Iatrogenic left internal mammary artery-coronary vein anastomosis treated with
covered stent deployment via retrograde percutaneous coronary sinus approach.
AB - OBJECTIVES: Percutaneous treatment of acquired coronary fistula with covered
stent BACKGROUND: Acquired aorto-coronary fistulae (ACF) is a rare complication
of coronary artery bypass graft (CABG) surgery. Surgical repair has been
generally recommended, but percutaneous techniques have also been described;
coils were used primarily in smaller fistula while double umbrella or vascular
occlusion devices were used in larger ones. To the best of our knowledge the use
of coronary covered stent has never been reported. A 73-year-old man underwent
CABG in November 2004 for unstable angina and left internal mammary artery (LIMA)
was anastomosed to left anterior descending (LAD) coronary artery. Three months
later he underwent a control angiogram to check for the reappearance of effort
angina, which demonstrated an inadvertent LIMA-great cardiac vein (GCV)
anastomosis. After discussions, an attempt to close the ACF with implantation of
a covered stent was performed. METHODS: Using a percutaneous right internal
jugular vein approach, coronary sinus was selectively cannulated and a 0.014-in.
coronary guide wire was advanced selectively to the GCV, then a covered stent was
deployed across the anastomotic site, obtaining the immediate occlusion of the
ACF. RESULTS: No contrast medium flowed into the distal part of the GCV at the
reinjection of the coronary sinus and a selective injection into LIMA showed the
absence of flow through LIMA, confirming the occlusion of the anastomotic site.
CONCLUSIONS: We have demonstrated successful occlusion of an iatrogenic ACF by
using percutaneous stenting of GCV with covered stent via coronary sinus
approach, which seems to be technically less demanding, safer, and time sparing.
PMID- 17039512
TI - Stent thrombosis following the STAR technique in a complex RCA chronic total
occlusion.
AB - Four drug-eluting stents were deployed in the right coronary artery (RCA) of a
symptomatic young woman who presented with a chronic total occlusion (CTO) of the
RCA. The occlusion was successfully crossed using the recently described STAR
technique. However, the patient died suddenly 15 hr later. Autopsy demonstrated a
long segment of subintimal stenting in the proximal and mid RCA that was
intraluminal in the distal vessel. Acute stent thrombosis in the subintimal
stents was responsible for sudden death. This case highlights the potential risk
of performing extensive subintimal stenting for CTO.
PMID- 17039513
TI - Platelet GPIIb/IIIa antagonist, XV459, in heparin-induced thrombocytopenia.
AB - Heparin-induced thrombocytopenia (HIT) is a serious, immune-related complication
of heparin therapy. One of the most severe manifestations of HIT is the
development of thromboembolic events, which is based on platelet activation and
aggregation caused by HIT-associated antibodies. Therapeutic options for patients
with HIT are limited despite advancement toward the development of alternative
(nonheparin) anticoagulants, such as direct thrombin inhibitors and indirect anti
factor Xa agents. Platelet GPIIb/IIIa receptor antagonists have been shown to be
the final common pathway for platelet aggregation regardless of the use of
activator or anticoagulant. In this study, the ability of a novel platelet
GPIIb/IIIa antagonist, a free acid form of roxifiban (XV459), to block platelet
activation/aggregation in response to highly characterized heparin-PF4 antibody
positive plasma/heparin was examined using light transmittance aggregometry,
serotonin release, and (125)I-fibrinogen binding assays to human platelets. XV459
at 20 nM maximally inhibited (P < 0.001) the platelet-activation/aggregation
responses as mediated by the HIT antibody-positive plasma (in the presence of
therapeutic heparin concentrations). Compared with controls, both HIT
antibodies/heparin and TEAC (a mixture of thrombin [0.1 IU/ml], epinephrine [1
microg/ml], arachidonate [0.1 mM], and collagen [10 microml]) resulted in
significantly higher levels of fibrinogen binding to human platelets (5-7-fold
increase; P < 0.001). Concentration-dependent profiles of XV459 on the mean
percent inhibition of (125)I-fibrinogen binding in the presence of HIT antibodies
and TEAC were achieved ( approximately 50% inhibition at 10 nM XV459). The
platelet GPIIb/IIIa receptor antagonist (XV459) might be of potential benefit in
the management of thrombotic thrombocytopenia produced by heparin and/or related
glycosaminoglycans.
PMID- 17039514
TI - Ad hoc percutaneous coronary interventions in patients with stable coronary
artery disease--a study of prevalence, safety, and variation in use from the
American College of Cardiology National Cardiovascular Data Registry (ACC-NCDR).
AB - OBJECTIVE: To utilize the American College of Cardiology National Cardiovascular
Data Registry (ACC-NCDR) to monitor the performance and safety of ad hoc PCIs.
BACKGROUND: The performance of ad hoc PCI remains controversial. Patients'
preference, cost, and vascular access issues favor an ad hoc strategy. Adequate
time for thoughtful decision-making, scheduling complexity, informed consent, and
physician reimbursement favor PCI on a subsequent day. METHODS: We analyzed
results in 68,528 patients with stable angina entered in the ACC-NCDR from 2001
2003. Ad hoc PCI was evaluated in many clinical and nonclinical subgroups. A
multivariable analysis was performed to determine whether ad hoc PCI had an
independent relationship with complications or procedure success. RESULTS:
Overall, 60.6% of patients underwent ad hoc PCI. There was no difference in ad
hoc PCI mortality, renal failure, or vascular complications from staged PCI. A
lower percentage of patients at high vs. low risk and with vs. without renal
failure underwent ad hoc PCIs (58.6% vs.63.0% and 50.7% vs. 60.9% respectively).
There was wide variation in the performance of ad hoc PCIs according to payer
(70.2-60.3%), hospital PCI volume (67-50.2%), hospital owner (89.7-59.6%), and
geographic area (75.5-47.4%). Ad hoc PCI per se was not independently related to
PCI success or complications. CONCLUSIONS: PCI success was related to
patient/lesion related factors and not to the performance of ad hoc PCIs per se.
Although ad hoc PCI can be performed in more patients than at present, this
strategy will never be possible in all patients at all times.
PMID- 17039515
TI - Hypocholesterolemia in chronic anemias with increased erythropoietic activity.
AB - Hypocholesterolemia of unknown etiology has been previously described in various
chronic anemias. Few small studies also suggested that those patients have a
lower incidence of atherosclerotic events. The aim of our study was to determine
the extent of hypocholesterolemia in various types of anemias. We studied 59
patients with chronic anemias associated with high-erythropoietic activity
(thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital
spherocytosis), 8 patients with low-erythropoietic activity anemias (acquired
aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy
controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low
density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin,
soluble transferrin receptor (STR), and serum erythropoietin levels were
determined in each patient. All patients with chronic anemia and increased
erythropoietic activity had hypocholesterolemia, whereas none of those with low
erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL
cholesterol, and LDL cholesterol levels were found to be significantly lower in
the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14
mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001,
respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01,
respectively). Significant inverse correlation (R2=0.507) was observed between
serum cholesterol and STR levels, which in the absence of iron deficiency reflect
bone marrow activity. Taken together, our results imply that hypocholesterolemia
accompanies anemias with high-erythropoietic activity. We suggest that the high
erythropoitic activity-associated hypocholesterolemia is due to increased
cholesterol requirements by the proliferating erythoid cells. Further studies are
needed to elucidate the exact mechanism and the possible clinical consequences of
this phenomenon.
PMID- 17039518
TI - Simultaneous diagnostic coronary angiography utilizing a single arterial access
technique.
PMID- 17039517
TI - Coronary artery perforation during interventional procedures.
PMID- 17039520
TI - Initial transcatheter palliation of hypoplastic left heart syndrome.
AB - Initial percutaneous transcatheter palliation of hypoplastic left heart syndrome
is now feasible. The primary procedures for palliation include stenting of the
ductus arteriosus with a self expanding nitinol stent to secure an adequate
systemic blood flow, placement of an internal pulmonary arterial band to protect
the pulmonary vascular bed and to prevent pulmonary overcirculation, and widening
of the interatrial communication by blade and balloon septostomy or static
balloon dilation to decompress the left atrium. Anatomic variations of the ductus
arteriosus have important implications for technical success with ductal
stenting. Patients who have undergone complete transcatheter palliation with the
internal pulmonary band appear to have less immediate morbidity at the time of
transplant, with preserved integrity and growth of the branch pulmonary arteries
at one year follow-up.
PMID- 17039519
TI - Eph-ephrin A system regulates murine blastocyst attachment and spreading.
AB - Although numerous adhesion molecules are expressed on mammalian endometrial
epithelial cells, there have not been any studies of a mechanism to prevent
premature attachment of the embryo. In this study, we examined the possible
involvement of Eph-ephrin interaction, which can induce repulsive forces. In
mice, Eph A1, A2, and A4 were expressed on endometrial epithelial cells and
ephrin A1-4 on blastocysts. Reverse transcriptase-polymerase chain reaction
showed that mRNA expression of ephrin A1-4 on embryos transiently decreased
around the implantation period. Immunohistochemistry demonstrated that the
expression of Eph A1 on endometrial epithelial cells and ephrin A1 and A3
expression on embryos decreased at implantation sites. Recombinant Eph A1 reacted
with cell the surface of ephrin A-bearing trophectoderm cells. Attachment assays
using Eph A1-coated dishes showed that blastocyst attachment was reversibly
inhibited by Eph A1. These findings suggest an important role of the Eph-ephrin A
system in regulating the initial embryo-maternal contact during the cross-talk
period that precedes embryo implantation.
PMID- 17039521
TI - Development of a reexpandable covered stent for children.
AB - The use of covered stents in children is limited by the need for a large long
sheath for delivery and the impossibility of redilation once implanted. The
authors developed a reexpandable covered stent implantable in children through a
small sheath and evaluated its clinical feasibility in mini piglets. An original
Palmaz stent was covered with a polyurethane membrane that could be stretched up
to 700%. Under general anesthesia, the authors implanted the covered stents in
six mini piglets using a long sheath with a diameter approximately 1 French
larger than the recommended size required to deliver an uncovered Palmaz stent.
The implantation technique was similar to conventional stent implantation. In six
piglets, the stent could be redilated from 7.5 to 8.7 mm 28-70 days after
implantation. Macroscopic and microscopic examination showed intimal coverage of
the coating with minimal inflammatory reaction around the stent. Our newly
designed reexpandable stent covered with a polyurethane membrane is promising for
use in children.
PMID- 17039522
TI - New clothes for covered stents.
PMID- 17039523
TI - Behavior of enteric neural crest-derived cells varies with respect to the
migratory wavefront.
AB - Neural crest-derived cells colonize the entire gastrointestinal tract. The
migration of these enteric neural crest-derived cells (ENCCs) occurs by their
formation of cellular strands that extend into the intestinal mesenchyme. We have
studied the behavior of crest cells that underlies the formation and extension of
these strands by time-lapse microscopy. ENCCs expressing fluorescent marker
molecules were visualized in situ in the embryonic mouse and chick gut. The major
contributor to strand extension is from cells located within a region
approximately 300 microm behind (rostral to) the most caudal cells in the
migratory wavefront. Cells in the region immediately behind the leading cell of
the strand either move intermittently in parallel with the leading cell, or
advance caudally toward the wavefront over other ENCCs. Another addition to the
strands arises from isolated cells located caudal to the wavefront. These cells
showed a range of behavior including attachment and separation from the strands.
The extending strands converged to form nodes, and then diverged along
independent paths to form new strands, a behavior suggestive of attraction and
repulsion. This behavior is probably responsible for the unique reticulated
arrangement of ganglia in the enteric nervous system. As cells become positioned
farther behind the wavefront, they exhibit more restricted movement and varied
trajectories. We conclude that ENCCs exhibit different behaviors, depending on
their position with respect to the wavefront. These different behaviors suggest a
critical role for cell-cell interaction in the migratory process.
PMID- 17039524
TI - Transcatheter patent foramen ovale closure using the Premere PFO occlusion
system.
AB - OBJECTIVES: To evaluate the safety and efficacy profile of the new Premere patent
foramen ovale (PFO) occlusion system. BACKGROUND: Several different devices have
been used so far for transcatheter PFO closure but no data has been published so
far on the efficacy and safety of the Premere PFO occlusion system. METHODS:
Since September 2005, 15 patients (seven males, eight females; mean age 51.2 +/-
10.8 years) at our institution underwent transcatheter PFO closure because of
cryptogenic stroke, using the Premere PFO occlusion system. The procedure was
performed under fluoroscopic and transesophageal echocardiographic (TEE) guidance
in all patients. Seven patients (47%) had an associated atrial septal aneurysm
and two patients had had >1 stroke. Five patients (33%) had an associated
thrombophilia, whereas three patients (20%) had a diagnosis of migraine headache
with aura, by the referring neurologist. Residual shunt was assessed immediately
after and 1 month (only in 11 patients) after the procedure by both transcranial
Doppler and TEE. RESULTS: Premere PFO devices could be implanted in all patients
(20 mm size in seven patients, 25 mm size in eight). Fluoroscopy time was 7.3 +/-
1.9 and procedural time was 11 +/- 3 min (range 7-17 min), reflecting our initial
learning curve with this device. No complication occurred during the procedure or
at follow-up. A residual shunt was noted immediately after the procedure in eight
patients (53%) and at 1 month in 4/11 patients (36%). Residual shunt was mild in
all patients. After a median follow-up of 4.2 months (0.2-5.8 months), no patient
had a recurrent stroke. All patients with migraine headache with aura had
resolution of symptoms. CONCLUSIONS: Our preliminary experience with the Premere
PFO occlusion system shows that this device is safe and effective.
PMID- 17039525
TI - Transcatheter closure versus medical therapy of patent foramen ovale and
cryptogenic stroke.
AB - OBJECTIVES: The purpose of this study was to evaluate the efficacy and safety of
device closure of patent foramen ovale (PFO) versus antiplatelet therapy in
patients with cryptogenic stroke (CS). BACKGROUND: There are no controlled data
to support the therapeutic value of PFO closure with a device compared to medical
treatment in patients with CS. METHODS: We performed a nonrandomized,
prospective, patient preference case series comparing the recurrence rate in 92
patients with PFO and CS who were treated either with antiplatelet agents (44
patients) or underwent catheter closure (48 patients) using the Amplatzer PFO
occluder (APFOO). All patients completed a 2-year follow-up. RESULTS: PFO closure
group. Immediate complete closure (CC) was observed in 44/48 (91%) patients. Four
(9%) patients had a minimal residual shunt immediately after the procedure. One
patient developed hemopericardium that was successfully managed by
pericardiocentesis. No other complication was observed. Follow-up. PFO closure
group. Contrast bubble study at 6-month follow-up confirmed CC in all 48
patients. No complications were observed. Antiplatelet therapy group. Three (6%)
and 6 (13%) patients had a major and minor hemorrhagic event, respectively. The
average incidence of embolic events/year was 0 and 14.75% for the PFO closure
group and the antiplatelet therapy group, respectively (P < 0.001). CONCLUSIONS:
PFO closure using the APFOO is a rational alternative to medical treatment in
patients with CS. Larger randomized clinical trials are required to support the
use of this device over the other PFO occluders and medical therapy.
PMID- 17039526
TI - Suture-mediated closure of a patent foramen ovale during surgery without
cardiopulmonary bypass.
AB - A patent foramen ovale (PFO) is associated with an increased risk of recurrent
ischemic strokes and transient ischemic attacks due to paradoxical emboli in
patients with prior neurological events. We report a case of a surgical suture
mediated of a PFO closure without cardiopulmonary bypass in a patient with
recurrent cerebral ischemic events, who was intolerant of medical therapy, was a
poor candidate for catheter-based PFO closure, and presented as a potentially
high risk for poor wound healing from traditional surgical closure.
PMID- 17039527
TI - Transcatheter closure of aortic sinus to left atrial fistula caused by erosion of
Amplatzer septal occluder.
AB - One year after Amplatzer device closure of an atrial septal defect, an aortic to
left atrial fistula was diagnosed in a patient who developed a new onset murmur
with no other symptoms. The fistula was closed with a 4-mm Amplatzer Septal
Occluder during a transcatheter procedure, avoiding the need for cardiac surgical
repair.
PMID- 17039528
TI - Late migration of a Sideris buttoned device for occlusion of atrial septal
defect.
AB - We describe a 17-year-old patient with an atrial septal defect who underwent
device closure with a second generation Sideris buttoned device at 4 years of
age. She presented 13 years after the procedure with the acute onset of chest
discomfort, at which time a chest radiograph showed migration of the wire of the
right atrial counter-occluder to the lateral aspect of the right atrial wall,
with an associated right atrial perforation. The patient underwent uneventful
surgical device retrieval and atrial septal defect closure. Late migration of a
portion of the Sideris buttoned device can occur, suggesting the need for
continued follow up, and a high index of suspicion for device failure should a
patient become symptomatic.
PMID- 17039529
TI - An 84-year-old patient with an atrial septal defect rescued using the Amplatzer
septal occluder device.
AB - We report the case of a rescued 84-year-old patient with atrial septal defect
(ASD) who was emergently admitted to our intensive care unit with progressive
dyspnea requiring mechanical ventilation for severe anoxia and respiratory
arrest. She had no history of congenital heart diseases. ECG and chest X-ray
revealed overload of the right atrium and ventricle, and severe increase in
pulmonary vascular markings. Transesophageal echocardiography showed a moderately
large size ASD (18 x 23 mm(2)). Hemodynamic evaluation documented an increase in
PA pressure of 37/16 mm Hg and Q(p)/Q(s) of 2.33. Her systemic condition did not
improve following diuretics, cathecholamine, and afterload-reducing substances.
She required mechanical ventilation for severe hypoxia. She underwent successful
closure of the ASD using an Amplatzer septal occluder on day 17. Hemodynamics and
findings on chest X-ray dramatically improved after this procedure. She was
discharged from the hospital on foot.
PMID- 17039530
TI - Failure of cutting balloon angioplasty to prevent restenosis in childhood
pulmonary venous stenosis.
AB - We describe bilateral pulmonary vein stenosis in a 5-year-old boy. He initially
presented with haemoptysis secondary to left upper lobe pulmonary vein atresia
and left lower lobe stenosis and subsequently he underwent left-sided
pneumonectomy. He underwent repeat cardiac catheterizations with repeated balloon
angioplasty of the right-sided venous stenoses using a cutting balloon. Despite
satisfactory initial results the pulmonary venous stenosis reoccurred as early as
2 months following balloon angioplasty. Although cutting balloon angioplasty has
demonstrated effective immediate alleviation of pulmonary venous stenosis its
utility in providing sustained improvement in pulmonary vein stenosis is limited.
PMID- 17039531
TI - Failure of cutting balloon angioplasty to prevent restenosis in childhood
pulmonary vein stenosis.
PMID- 17039532
TI - Reproducible microvascular dysfunction with dobutamine infusion in Takotsubo
cardiomyopathy presenting with ST segment elevation.
AB - Takotsubo (ampulla) cardiomyopathy, or broken heart syndrome, is an
underrecognized cardiac illness that usually presents as an acute coronary
syndrome in postmenopausal females. The disorder is frequently associated with
episodes of mental or physical stress, implicating an abnormal cardiac response
to increased catecholamines. Although death has been reported during the index
event, the long-term prognosis is good with full recovery of left ventricular
function. We present a case of Takotsubo cardiomyopathy mimicking anterior ST
segment elevation myocardial infarction precipitated by dobutamine stress
testing. Reinfusion of dobutamine in the catheterization laboratory reproduced
symptoms with angiography and intravascular ultrasound supporting the theory of
abnormal microvascular circulation as the etiology of Takotsubo cardiomyopathy.
Acute and delayed magnetic resonance imaging demonstrated no infarction with
complete recovery of ventricular function.
PMID- 17039533
TI - Improvement of biventricular function after transcatheter closure of atrial
septal defect: a case report.
AB - We report a 17-year-old man presented with palpitation. Echocardiography
demonstrated secundum atrial septal defect (ASD) with marked right sided
dilatation, indicating significant left to right intracardiac shunting. Cardiac
magnetic resonance imaging performed 3 months after transcatheter ASD closure
demonstrated marked improvement in biventricular systolic function.
PMID- 17039534
TI - Specific integrin subunits in bovine oocytes, including novel sequences for alpha
6 and beta 3 subunits.
AB - Integrins facilitate attachment of cells to the extra-cellular matrix, often
binding the arginine-glycine-aspartic acid tri-peptide motif, thus facilitating
cell migration, mediating cell-cell adhesion, linking the extracellular matrix
(ECM) with cytoskeletal elements, and acting as signaling molecules. Adhesion
activates signaling mechanisms that regulate integrin function, cytoskeletal
assembly, cell behavior, and protein synthesis. Immunofluorescence was used to
determine the presence of integrin alpha and beta subunits on the surface of
bovine oocytes using a panel of monoclonal antibodies (mAbs) specific for alphaL,
alphaM, alphaX, alphaV, alpha2, alpha4, alpha6, beta1, beta2, and beta3 antigens,
with multiple antibodies for each subunit. Confocal microscopy indicated the
presence of alphaV, alpha6, alpha4, alpha2, ss1, and ss3 integrin subunits on the
plasma membrane of bovine oocytes. The presence of these subunits was verified by
RT-PCR analysis using primers designed based on known gene sequences of bovine
integrin subunits, or by using sequence information using bovine expressed
sequence tags (EST) compared with known human and murine integrin subunit gene
sequence information. Previously unpublished sequence information for bovine
alpha6 and beta3 integrins was determined. The presence of these integrin
subunits on the bovine oocyte vitelline membrane supports the hypothesis that
sperm-oocyte interactions in the bovine are mediated by integrins.
PMID- 17039535
TI - Donor cell differentiation, reprogramming, and cloning efficiency: elusive or
illusive correlation?
AB - Compared to other assisted reproductive technologies, mammalian nuclear transfer
(NT) cloning is inefficient in generating viable offspring. It has been
postulated that nuclear reprogramming and cloning efficiency can be increased by
choosing less differentiated cell types as nuclear donors. This hypothesis is
mainly supported by comparative mouse cloning experiments using early
blastomeres, embryonic stem (ES) cells, and terminally differentiated somatic
donor cells. We have re-evaluated these comparisons, taking into account
different NT procedures, the use of donor cells from different genetic
backgrounds, sex, cell cycle stages, and the lack of robust statistical
significance when post-blastocyst development is compared. We argue that while
the reprogrammability of early blastomeres appears to be much higher than that of
somatic cells, it has so far not been conclusively determined whether
differentiation status affects cloning efficiency within somatic donor cell
lineages.
PMID- 17039536
TI - Transcatheter closure of secundum atrial septal defects.
PMID- 17039537
TI - Diagnostic utility of the two methods of ankle brachial index in the detection of
peripheral arterial disease of lower extremities.
AB - BACKGROUND: Peripheral arterial disease (PAD) is a common disease that is
diagnosed with a screening test called the Ankle Brachial Index (ABI). Different
methods of ABI have been described in the literature. We wanted to estimate and
compare the sensitivity and specificity of an alternative method of calculating
the ABI (LAP ABI, low ankle pressure ABI) with the current method (named high
ankle pressure (HAP)), using digital subtraction angiography (DSA) as the gold
standard. METHODS: We reviewed the records of all patients who had undergone DSA
at a major academic center between August 2003 and October 2005. The study
includes 107 patients/208 limbs. Inclusion criteria included patients with an ABI
performed within 30 days prior to the DSA. Patients with non-compressible vessels
and ABI >1.40 were excluded. Abnormal ABI was defined as < or = 0.9 for both
methods. Disease on angiogram was defined as the presence of 50% or more stenosis
of any lower extremity artery from the aorto-iliac bifurcation to the ankle
arteries. RESULTS: The sensitivity of the HAP and LAP ABI for the diagnosis of
PAD was 69 and 84%, respectively (P < 0.001). The specificity of the HAP and the
LAP method was 83 and 64% respectively (P < 0.01). The overall accuracy of LAP
ABI and HAP ABI was 80 and 72%, respectively. CONCLUSIONS: The LAP ABI has better
sensitivity and overall accuracy in comparison to the HAP ABI to diagnose PAD.
PMID- 17039539
TI - Percutaneous closure of a para-anastomotic abdominal aortic graft leak.
AB - Para-anastomotic graft leaks are a potential complication following surgical
repair of an aortic aneurysm. Reoperation may be associated with significant
morbidity and mortality. We report successful percutaneous transcatheter closure
of an anastomotic graft leak utilizing an occluder device.
PMID- 17039538
TI - Sirolimus for below the knee lesions: mid-term results of SiroBTK study.
AB - OBJECTIVES: To assess the safety and efficacy of sirolimus-eluting stents (SESs)
in the treatment of severe intermittent claudication and critical limb ischaemia
with "below-the-knee" lesions, unsuitable for surgery. BACKGROUND: Limited
published evidence suggests that drug-eluting stents may offer significant
improvements in the treatment of infrapopliteal lesions. METHODS: Thirty
consecutive patients with either severe intermittent claudication or critical
limb ischemia (CLI), category 3-6 of Rutherford classification, and multivessel
disease of infrapopliteal arteries (> or = 2 vessels) were treated with SES.
Sixty-two arteries were treated with 106 SES. Mean age was 73.9 years, 77% of
patients were male and 36% diabetic. The primary endpoint was clinical
improvement and healing of ulcers at short term (1 month) and mid term (7.7
months). The secondary endpoint was primary vessel patency rate (angiographic or
duplex assessment). All patients received clopidogrel (75 mg daily) or
ticlopidine (150 mg daily) for 2 months or longer. RESULTS: Angiographic and
procedural success was achieved in all patients. At 7 months (7.7 +/- 5.8), it
was necessary to amputate 1 toe in one patient and 1 mid-foot in another. Limb
salvage was obtained in 100% of patients. Other events were: two cardiac deaths
unrelated to CLI, one stroke with hemiparesia, one initial reperfusion syndrome,
one contralateral CLI, and three recurrent homolateral claudication cases. All
surviving patients had a mid-term clinical improvement with 97% of primary
patency (56 patent arteries on 58 arteries). CONCLUSION: Treatment of "below-the
knee" lesions with SES may provide an alternative treatment for patients with
CLI.
PMID- 17039540
TI - Update of carotid stent trials.
AB - As is the case in many vascular territories, endovascular treatment of
extracranial carotid artery disease is becoming a rival alternative to surgery.
Results of carotid artery stenting (CAS) are improving with the introduction of
embolic protection devices, improved technology, and increasing operator
experience. Multiple clinical studies have shown results in favor of CAS as
opposed to carotid endarterectomy (CEA) in patients considered at high risk for
surgery. Current ongoing trials are examining both treatment options in low and
intermediate risk patients in prospective randomized protocols. With the recent
FDA approval of carotid stent systems, we are entering a new era in the treatment
of carotid artery disease. An update of modern carotid stent studies, as well as
stent versus surgery studies in the current era is needed.
PMID- 17039541
TI - Gadolinium-based contrast agents and nephrotoxicity.
PMID- 17039544
TI - The Cath Lab Crew: your second family.
PMID- 17039546
TI - Systematic comparison of catalytic mechanisms of hydrolysis and transfer
reactions classified in the EzCatDB database.
AB - Catalytic mechanisms of 270 enzymes from 131 superfamilies, mainly hydrolases and
transferases, were analyzed based on their enzyme structures. A method of
systematic comparison and classification of the catalytic reactions was
developed. Hydrolysis and transfer reactions closely resemble one another,
displaying common mechanisms, single displacement, and double displacement. These
displacement mechanisms might be further subclassified according to the type of
catalytic factors and nucleophilic substitution involved. Several types of
catalytic factors exist: nucleophile, acid, base, stabilizer, modulator,
cofactors. Nucleophilic substitution might be categorized as S(N)1/S(N)2 (or
dissociative/associative) reactions. The classification indicates that some
mechanisms favor particular types of catalytic factors. In hydrolyses of amide
bonds and phosphoric ester bonds, mechanisms with single displacement tend to use
inorganic cofactors such as zinc and magnesium ions as important catalysts,
whereas those with double displacement frequently do not use such cofactors. In
contrast, hydrolyses of O-glycoside bond rarely use such cofactors, with one
exception. The trypsin-like hydrolytic reaction, which is catalyzed by the
classic catalytic triad comprising serine/histidine/aspartate, can be considered
as a "super-reaction" because it is observed in at least three nonhomologous
enzymes, whereas most reactions are singlets without any nonhomologous enzymes.
By dividing complex reactions into several reactions, correlations between active
site structures and catalytic functions can be suggested. This classification
method is applicable to other reactions such as elimination and isomerization.
Furthermore, it will facilitate annotation of enzyme functions from 3D patterns
of enzyme active sites. The classification is available at
http://mbs.cbrc.jp/EzCatDB/RLCP/index.html.
PMID- 17039547
TI - Computational basis of knowledge-based conformational probabilities derived from
local- and long-range interactions in proteins.
AB - The probabilities of the various basins in Ramachandran maps are examined
critically. The theoretical basis of probability calculations both from molecular
computations and from protein libraries are discussed. The well-defined basins of
the Ramachandran maps are treated as rotational isomeric states. Statistical
independence and dependence of the states of different residues along the peptide
chain are discussed. The Flory isolated pair hypothesis, near neighbor
correlations, context effects, and long-range correlations are examined
critically. A method of evaluating long-range correlations in helical and
extended sequences is introduced in analogy with earlier polymer theory. Three
different protein libraries are constructed where data is considered from
residues in the (i) coiled regions, (ii) all regions, and (iii) only the helical
and extended regions of proteins. Singlet and pairwise dependent probabilities
calculated from these libraries are used to predict whether a given sequence is
helical or extended. Predictions using pairwise dependence were not better than
those using singlet probabilities. Modeling of long-range correlations improved
the predictions significantly. Removal of the Chameleon sequences from the data
set also improved the predictions, but to a lesser extent.
PMID- 17039548
TI - FiberID--a technique to identify fibrous protein subclasses.
AB - Fibrous proteins such as collagen, silk, and elastin play critical biological
roles, yet they have been the subject of few projects that use computational
techniques to predict either their class or their structure. In this article, we
present FiberID, a simple yet effective method for identifying and distinguishing
three fibrous protein subclasses from their primary sequences. Using a
combination of amino acid composition and fast Fourier measurements, FiberID can
classify fibrous proteins belonging to these subclasses with high accuracy by
using two standard machine learning techniques (decision trees and Naive Bayesian
classifiers). After presenting our results, we present several fibrous sequences
that are regularly misclassified by FiberID as sequences of potential interest
for further study. Finally, we analyze the decision trees developed by FiberID
for potential insights regarding the structure of these proteins.
PMID- 17039549
TI - Origin and characteristics of glycogen cells in the developing murine placenta.
AB - The junctional zone (Jz) of the mouse placenta consists of two main trophoblast
populations, spongiotrophoblasts and glycogen cells (GCs), but the development
and function of both cell types are unknown. We conducted a quantitative analysis
of GC size, number, and invasion of cells into the decidua across gestation.
Furthermore, we identified markers of GC function to investigate their possible
roles in the placenta. While the spongiotrophoblast cell volume doubles, and cell
number increases steadily from E12.5 to E16.5, there is a remarkable 80-fold
increase in GC numbers. This finding is followed by a notable decrease by E18.5.
Surprisingly, the accumulation of GCs in the decidua did not fully account for
the decrease in GC number in the Jz, suggesting loss of GCs from the placenta.
Glucagons were detected on GCs, suggesting a steady glucose release throughout
gestation. Connexin31 staining was shown to be specific for GCs. GC migration and
invasion may be facilitated by temporally regulated expression of matrix
metalloproteinase 9 and the imprinted gene product, Decorin. Expression of the
clearance receptor for type II insulin-like growth factor (IGF-II), IGF2R, in a
short developmental window before E16.5 may be associated with regulating the
growth effects of IGF-II from glycogen cells and/or labyrinthine trophoblast on
the expansion of the Jz. Thus stereology and immunohistochemistry have provided
useful insights into Jz development and function of the glycogen cells.
PMID- 17039551
TI - Hydrogen peroxide synthesis: an outlook beyond the anthraquinone process.
AB - Hydrogen peroxide (H2O2) is widely used in almost all industrial areas,
particularly in the chemical industry and environmental protection. The only
degradation product of its use is water, and thus it has played a large role in
environmentally friendly methods in the chemical industry. Hydrogen peroxide is
produced on an industrial scale by the anthraquinone oxidation (AO) process.
However, this process can hardly be considered a green method. It involves the
sequential hydrogenation and oxidation of an alkylanthraquinone precursor
dissolved in a mixture of organic solvents followed by liquid-liquid extraction
to recover H2O2. The AO process is a multistep method that requires significant
energy input and generates waste, which has a negative effect on its
sustainability and production costs. The transport, storage, and handling of bulk
H2O2 involve hazards and escalating expenses. Thus, novel, cleaner methods for
the production of H2O2 are being explored. The direct synthesis of H2O2 from O2
and H2 using a variety of catalysts, and the factors influencing the formation
and decomposition of H2O2 are examined in detail in this Review.
PMID- 17039552
TI - Detection of nitric oxide release from single cells by using constant-distance
mode scanning electrochemical microscopy.
PMID- 17039550
TI - Candidate regulators of mammary branching morphogenesis identified by genome-wide
transcript analysis.
AB - The mammary gland develops in a process known as branching morphogenesis, whereby
a distal epithelial bud extends and bifurcates to form an extensive ductal
network. Compared with other branched organs, such as the lung and kidney, little
is known about the molecular basis of branching in the mammary gland. Here we
report a microarray profiling strategy to identify novel genes that may regulate
mammary branching. We microdissected terminal end bud (TEB) and mature duct
microenvironments from beta-actin-green fluorescent protein reporter mice and
compared their RNA expression profiles with epithelium-free mammary stroma by
means of microarray. We identified 1,074 genes enriched in the TEB
microenvironment, 222 genes enriched in the mature duct microenvironment, and 385
genes enriched in both TEB and mature duct microenvironments. The microarray
correctly predicted the expression of genes known to be enriched in the
epithelium (Ets-5) and stroma (MMP-14) of TEBs and in the mature duct
microenvironment (MMP-3). The microarray also correctly predicted the
localization of previously uncharacterized genes, such as the TEB-enriched SPRR
1a, the duct-enriched casein-gamma, and the general epithelial marker
pleiotrophin. Analysis of genes enriched in TEBs revealed several genes in the
Wnt (Wnt-2, Wnt-5a, Wnt-7b, Dsh-3, Frizzled-1, Frizzled-2), hedgehog (Dhh),
ephrin (Ephrin-B1, Eph-A2), and transcription factor (Twist-1, Twist-2, Snail)
families. In situ hybridization verified that these genes were enriched in the
TEB epithelium (Wnt-5a, Wnt-7b, Dhh, Eph-A2) or TEB stroma (Wnt-2, Frizzled-1,
Ephrin-B1). We discuss the potential roles of these genes in mammary branching
morphogenesis.
PMID- 17039553
TI - Polymer brushes as ionotropic matrices for the directed fabrication of
microstructured calcite thin films.
PMID- 17039554
TI - Tailor-made onionlike stereocomplex crystals in incompatible, enantiomeric,
polylactide-containing block copolymer blends.
PMID- 17039555
TI - A highly reactive and stereoselective beta-mannopyranosylation system: mannosyl 4
pentenoate/PhSeOTf.
PMID- 17039556
TI - A tosylimido analogue of a nonheme oxoiron(IV) complex.
PMID- 17039557
TI - Cyclic carbodiphosphorane-diphosphinocarbene thermal interconversion.
PMID- 17039558
TI - Catalytic enantioselective domino oxa-michael/aldol condensations: asymmetric
synthesis of benzopyran derivatives.
AB - The first direct organocatalytic asymmetric domino oxa-Michael/aldol condensation
reaction is presented. The unprecedentedly simple, chiral, pyrrolidine-catalyzed
asymmetric domino reactions between salicylic aldehyde derivatives and alpha,beta
unsaturated aldehydes proceed with high chemo- and enantioselectivities to give
the corresponding chromene-3-carbaldehyde derivatives in high yields and with ee
values of 83-98%.
PMID- 17039559
TI - Direct catalytic enantioselective alpha-aminomethylation of aldehydes.
AB - The direct catalytic asymmetric alpha-aminomethylation of aldehydes is presented.
The chiral amine and amino acid catalyzed reactions between unmodified aldehydes
and a formaldehyde-derived imine precursor were fast and proceeded with high
chemo- and enantioselectivities. The corresponding dibenzyl-protected gamma-amino
alcohols were isolated in high yields with up to 98% ee after in situ reduction.
The reaction is a novel entry to valuable beta(2)-amino acid derivatives.
PMID- 17039560
TI - On the first polyarsenic organic compound from nature: arsenicin A from the New
Caledonian marine sponge Echinochalina bargibanti.
AB - Reported here is the first polyarsenic compound ever found in nature. Denominated
arsenicin A, it was isolated along a bioassay-guided fractionation of the organic
extract of the poecilosclerid sponge Echinochalina bargibanti collected from the
north-eastern coast of New Caledonia. In defining an adamantine-type polyarsenic
structure for this compound, deceptively simple NMR spectra were complemented by
extensive mass spectral analysis. However, it was only the synthesis of a model
compound that provided the basis to discriminate structure 4 from other
spectrally compatible structures for arsenicin A; to this end, a comparative ab
initio simulation of IR spectra for the natural and the synthetic compounds was
decisive. Arsenicin A is endowed with potent bactericidal and fungicidal
activities on human pathogenic strains. All this may revive pharmacological
interest in arsenic compounds while prompting us to rethink the arsenic cycle in
nature.
PMID- 17039561
TI - Enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl
ketones catalyzed by bifunctional organocatalysts.
AB - A highly enantioselective Michael addition of alpha-substituted cyanoacetates to
vinyl ketones was accomplished in the presence of simple bifunctional
thiourea/tertiary amine organocatalysts. A number of alpha-aryl or alkyl
cyanoacetates have been successfully applied to give multifunctional compounds
with an all-carbon-substituted quaternary stereocenter in excellent
enantioselectivities (82-97 % ee) and yields (61-99 %). The optical pure adducts
could be smoothly converted to variously structured beta(2,2)-amino acid esters.
Moreover, an interesting reaction model involving multiple hydrogen-bonding
interactions amongst the thiourea/tertiary amine catalyst and the reactants has
been proposed based on the absolute configuration of the adduct and computational
studies.
PMID- 17039563
TI - NFAT transcription factors in control of peripheral T cell tolerance.
AB - The Ca++-regulated calcineurin/NFAT cascade is one of the crucial signalling
pathways that controls adaptive immunity. However, a number of novel experimental
data suggest that, in addition to their role in T cell activation, NFATc
transcription factors play also a decisive role in the generation of peripheral
tolerance against self-antigens. This function of NFATc factors is mediated by
controlling activation-induced cell death and clonal anergy of T helper cells and
the activity of regulatory T cells. The multi-functional role of NFATc proteins
characterize these transcription factors as key regulators of immunological
tolerance and, if dysregulated, of development of autoimmune diseases.
PMID- 17039562
TI - Highly efficient syntheses of hyaluronic acid oligosaccharides.
AB - Highly efficient syntheses of hyaluronic acid oligosaccharides have been
accomplished through the pre-activation based iterative one-pot strategy. A
series of oligosaccharides ranging from di- to hexasaccharides were rapidly
assembled using only near stoichiometric amounts of the building blocks without
aglycon adjustment or purifications of intermediate oligosaccharides.
Deprotection and oxidation protocols were developed for protective group removal
and oxidation-state adjustment. The availability of such structurally well
defined synthetic hyaluronic acid oligosaccharides will greatly facilitate the
establishment of detailed structure-function relationships.
PMID- 17039564
TI - Cross-presentation of antigens from apoptotic tumor cells by liver sinusoidal
endothelial cells leads to tumor-specific CD8+ T cell tolerance.
AB - Development of tumor-specific T cell tolerance contributes to the failure of the
immune system to eliminate tumor cells. Here we report that hematogenous
dissemination of tumor cells followed by their elimination and local removal of
apoptotic tumor cells in the liver leads to subsequent development of T cell
tolerance towards antigens associated with apoptotic tumor cells. We provide
evidence that liver sinusoidal endothelial cells (LSEC) remove apoptotic cell
fragments generated by induction of tumor cell apoptosis through hepatic NK1.1+
cells. Antigen associated with apoptotic cell material is processed and cross
presented by LSEC to CD8+ T cells, leading to induction of CD8+ T cell tolerance.
Adoptive transfer of LSEC isolated from mice challenged previously with tumor
cells promotes development of CD8+ T cell tolerance towards tumor-associated
antigen in vivo. Our results indicate that hematogenous dissemination of tumor
cells, followed by hepatic tumor cell elimination and local cross-presentation of
apoptotic tumor cells by LSEC and subsequent CD8+ T cell tolerance induction,
represents a novel mechanism operative in tumor immune escape.
PMID- 17039565
TI - Mice expressing high levels of soluble CD14 retain LPS in the circulation and are
resistant to LPS-induced lethality.
AB - Despite significant progress in understanding the origin of soluble CD14 (sCD14),
its physiological function remains largely unknown. Recent research has produced
contradictory observations suggesting that sCD14 may have either beneficial or
detrimental properties in protection against LPS-induced endotoxin shock. To
resolve this controversy and to establish a mouse model suitable for elucidation
of the functions of human CD14 (hCD14) in vivo, we generated several lines of
transgenic mice bearing different copy numbers of the hCd14 transgene on a murine
Cd14-/- background. The hCD14 was entirely capable of complementing loss of mouse
CD14 to mediate cellular responses to LPS. Serum levels of sCD14 in a founder
with multiple copies of the transgene were several times higher than in
transgenic animals with a single copy of Cd14. Furthermore, mice with high levels
of hCD14 were hypo-responsive to LPS and survived a lethal dose of LPS. Further
inquiry into the mechanism of the hypo-response to LPS revealed that protection
is associated with the higher amounts of circulating LPS. Most of this
circulating LPS can be immunoprecipitated with anti-CD14 antibodies. These
results suggest that sCD14 blocks circulating LPS by limiting the amount of
monocyte-bound LPS and thus reduces inflammatory responses.
PMID- 17039566
TI - The role of the ICOS/B7RP-1 T cell costimulatory pathway in murine experimental
autoimmune uveoretinitis.
AB - ICOS/B7RP-1 is a new member of the CD28/B7 family of costimulatory molecules and
plays differential roles in autoimmune diseases. In this study, we examined the
role of ICOS/B7RP-1 pathway in the pathogenesis of mouse experimental autoimmune
uveoretinitis (EAU), an animal model of human autoimmune uveitis. ICOS expression
was found on infiltrating CD4+ T cells in the region of the retina in EAU-induced
mice. The anti-B7RP-1 monoclonal antibody (mAb)-treated or ICOS-deficient mice
showed a substantial reduction of disease scores. Blockade of ICOS/B7RP-1
interaction during the effector phase ameliorated the disease, whereas its
blockade during the induction phase exhibited no significant effect. Moreover,
administration of anti-B7RP-1 mAb effectively ameliorated the disease induced by
adoptive transfer of pathogenic T cells. The anti-B7RP-1 mAb treatment inhibited
the expansion and/or effector function of pathogenic T cells, given that
proliferative response and IFN-gamma production by lymph node cells were reduced
upon restimulation with the antigen peptide in vitro. These results suggest that
the ICOS/B7RP-1 interaction plays a critical role in the pathogenesis of uveitis.
We also indicated that ICOS-mediated costimulation plays differential roles in
EAU and experimental autoimmune encephalomyelitis, which is also a Th1 disease
induced in the same manner as EAU.
PMID- 17039567
TI - A critical role for ICOS co-stimulation in immune containment of pulmonary
influenza virus infection.
AB - Lung pathology observed during influenza infection is due to direct damage
resulting from viral replication and bystander damage caused by overly exuberant
antiviral immune mechanisms. In the absence of universally effective vaccines and
antiviral therapies, knowledge of the cellular components required for immune
containment of influenza is essential. ICOS is a late co-stimulatory molecule
expressed by T cells 12-24 h after activation. We show for the first time that
inhibition of ICOS with a monoclonal antibody reduces pulmonary T cell
inflammation and associated cytokine expression. Surprisingly however, this
reduction in T cells was not accompanied by an alleviation of weight loss and
illness. Furthermore, lung viral titres were elevated following anti-ICOS
treatment, suggesting that the beneficial outcome of reducing T cell pathology
was masked by enhanced virus-induced damage and innate inflammation. This study
demonstrates the delicate balance that exists between pathogen burden and
pulmonary T cell inflammation during influenza infection and highlights the
critical role of ICOS in this response.
PMID- 17039568
TI - In vivo CD44-CD49d complex formation in autoimmune disease has consequences on T
cell activation and apoptosis resistance.
AB - CD44 is involved in leukocyte migration and activation and has recently been
reported to contribute to leukocyte extravasation by associating with CD49d. We
explored whether similar changes in CD44 activity are seen in vivo using murine
alopecia areata (AA) as a chronic, organ-related autoimmune disease model system.
Expression of the activated, hyaluronan-binding form of CD44, and of CD49d, was
elevated in draining lymph node cells (LNC) of AA-affected mice as compared to
control mice. LNC of AA mice displayed increased motility, proliferative activity
and apoptosis resistance, which were equally well inhibited by anti-CD44 and anti
CD49d. The latter is the sequelae of the association between CD44 and CD49d that
is seen in activated lymphocytes. Significantly, due to CD44-CD49d complex
formation, CD44 gains access to focal adhesion kinase and CD49d gains access to
CD44-associated lck and ezrin, such that downstream kinases become activated via
CD44 or CD49d engagement. Thus, by their association, CD44 and CD49d mutually
avail themselves of the partner's signaling pathways and the ligand binding of
each one triggers signaling pathways of both. This strongly influences the
lymphocytes' activation state and function.
PMID- 17039569
TI - Spontaneous class switching and B cell hyperactivity increase autoimmunity
against intracellular self antigen in Lyn-deficient mice.
AB - IgG autoantibodies cause pathology due to their ability to bind self antigens.
However, the extent to which the initial B cell activation and isotype switching
is antigen-driven is unclear and it has been widely proposed that intrinsic B
cell hyperactivity may be a contributing factor. To explore this issue we
generated mice with B cell hyperactivity secondary to deficiency in the src
kinase Lyn that also expressed a gene-targeted anti-hen egg lysozyme Ig construct
(VDJkappa) capable of class switching to all isotypes. The B cell hyperactivity
caused spontaneous hypersecretion of antibodies and class switching to IgM, IgA,
IgG1 and IgG3 isotypes in the absence of self antigen, and this persisted as an
autoimmune phenomenon in the presence of intracellularly expressed hen egg
lysozyme. Exaggerated class switching was also unaffected by antigen in vitro.
These findings show that systemic high-avidity intracellular self antigens do not
induce self tolerance in the face of B cell hyperactivity. Under these
circumstances, spontaneous activation of hyperactive B cells leads to isotype
switching and the development of high titres of IgG autoantibodies against
intracellular proteins.
PMID- 17039570
TI - Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune
myocarditis.
AB - The most common reason for heart failure in young adults is dilated
cardiomyopathy often resulting from myocarditis. Clinical studies and animal
models provide evidence that an autoimmune response against heart myosin is the
underlying reason for the disease. IL-12 has been suggested to play a key role in
development of experimental autoimmune myocarditis (EAM), as IL-12p40 and IL
12Rbeta1 knockouts are protected from disease. In this study, we have compared IL
12p40-/- mice, IL-12p35-/- mice and mice treated with a neutralizing IL-23
antibody in EAM and found that in fact IL-23, not IL-12, is responsible for
inflammatory heart disease. However, these cytokines appear to have redundant
activity for priming and expansion of autoreactive CD4 T cells, as specific T
cell proliferation was only defective in the absence of both cytokines. IL-23 has
been suggested to promote a pathogenic IL-17-producing T cell population. We
targeted IL-17 by capitalizing on an active vaccination approach that effectively
breaks B cell tolerance. Neutralization of IL-17 reduced myocarditis and heart
autoantibody responses, suggesting that IL-17 is the critical effector cytokine
responsible for EAM. Thus, targeting of IL-23 and IL-17 by passive and active
vaccination strategies holds promise as a therapeutic approach to treat patients
at risk for development of dilated cardiomyopathy.
PMID- 17039571
TI - A note on cointegration of health expenditures and income.
AB - Utilizing a panel data set of 50 US states, this note investigates
nonstationarity and cointegration of health care expenditures and gross state
products (GSP). Both the individual state-based method and the recent panel data
method are applied. Allowing for structural breaks in the test, we find that
health care expenditures and GSP are both nonstationary. The evidence also
suggests that the two series form a cointegrating relationship. The income
elasticities of health spending vary over states and became smaller in the 1990s.
PMID- 17039572
TI - An empirical analysis of US and Japanese health insurance using age-period-cohort
decomposition.
AB - Aggregate data on household health insurance expenditure in the US and Japan that
are classified by period and age are decomposed into age, period, and cohort
effects by using the Bayesian cohort models. These models are developed to
overcome the identification problem involved in cohort analysis. Despite the
differences between the health insurance systems of the two countries, three
interesting empirical findings are obtained. First, in both the countries, the
age effects are the most influential, and the cohort effects have negligible
influence. The latter provides a striking policy implication since the
generational imbalance in social security expenditures is widely recognized in
developed countries. Second, in both the countries, the period effects show a
roughly upward trend. Finally, the age effects exhibit a roughly upward movement
for all age groups in the US; however, in Japan, these effects show a downward
movement for the 55-59 age group due to the changes in the health insurance
system on retirement.
PMID- 17039573
TI - Unrelated medical care in life years gained and the cost utility of primary
prevention: in search of a 'perfect' cost-utility ratio.
AB - An important subject of debate in cost-utility analysis of health care programmes
is whether to include costs of unrelated medical care in life years gained. The
inclusion of such costs is likely to be of consequence in the case of primary
prevention. This paper presents different strategies regarding the inclusion not
only of the costs, but also of the health effects of unrelated medical care in
economic evaluations. Four different cost-utility ratios are presented and
related to the criterion of internal consistency. In addition, the possibility to
relate the ratios to a well-posed decision problem is analysed. An example
computes the different ratios for smoking cessation interventions in different
age groups. Including health care costs of unrelated medical care in life years
gained increases cost utility ratios, but excluding unrelated medical costs
favours smoking cessation interventions targeted at older smokers over those at
younger smokers. We conclude that for primary prevention only a cost utility
ratio that includes both the costs and effects of unrelated medical care meets
the criterion of internal consistency and is related to a meaningful decision
problem. Therefore, this type of cost-utility ratio should be preferred even if
the data requirements may be substantial.
PMID- 17039574
TI - Vinyl polymers as non-viral gene delivery carriers: current status and prospects.
AB - Since the first application of polymers as non-viral gene delivery systems in
1965 by Vaheri and Pagano using functionalised dextran (A. Vaheri and J. S.
Pagano, "Infectious poliovirus RNA: a sensitive method of assay", Virology 1965,
27, 434-6), a large number of different polymers have been developed, studied and
compared for application as DNA carriers. Vinyl-based polymers are one type of
polymers that have gained considerable interest. The interest in developing this
particular type of polymer is partly related to the straightforward way in which
large amounts of these polymers can be prepared by radical (co)polymerisation.
This opens up a path for establishing a wide range of structure-property
relations using polymer libraries. The present review aims to give an overview of
past and ongoing research using vinyl-based gene delivery systems. The
application of cationic, neutral and zwitterionic polymers as DNA carriers is
summarised and discussed. [structure: see text] Chemical structure of DEAE
functionalised dextran.
PMID- 17039575
TI - Measuring cell adhesion on RGD-modified, self-assembled PEG monolayers using the
quartz crystal microbalance technique.
AB - In this study, the suitability of a flow-through quartz crystal microbalance
system for the detection of the adhesion of rMSCs and 3T3-L1 fibroblasts on
different surfaces is demonstrated. Frequency shifts for rMSCs of -6.7 mHz x
cell(-1) and -2.0 mHz x cell(-1) for 3T3-L1 cells could be detected on non
modified gold sensors, revealing that the frequency shift per cell is comparable
to that of a static setup. Modifying the sensor surface with SAMs of
thioalkylated omega-amine-terminated PEG derivatives led to cell-adhesion
resistant surfaces. Total frequency shifts of only -20 +/- 7 Hz showed that
protein adsorption was also significantly reduced. Attaching 35 pmol x mm(-2) of
the GRGDS cell adhesion motif to the SAMs induced specific cell adhesion due to
RGD-integrin interactions; the resonance frequency dropped by 3.4 mHz x cell(-1).
Furthermore, the kinetics of cell detachment could be determined. The
corresponding processes were completed after 10 min for trypsin, and not before
90 min with GRGDS. Moreover, the detectability of cell adhesion was shown to
increase after the addition of manganese cations. The total decrease in the
resonance frequency was almost 80 Hz in the presence of Mn(2+) (6.4 mHz x cell(
1)). [image: see text] Staining the cytoskeleton of the rMSCs shows that the
GRGDS-modified surfaces are almost completely covered with well-spread cells.
PMID- 17039576
TI - Rapid and efficient enzyme encapsulation in a dendrimer silica nanocomposite.
AB - We report the entrapment of horseradish peroxidase and quantitative encapsulation
of glucose oxidase within silica nanoparticles by utilizing an amine-terminated
dendritic template. Our improved strategy employs a water-soluble biomimetic
template which is able to catalyze the condensation of Si(OH)(4) to silica
nanoparticles while trapping an enzyme inside the mesoporous material. Kinetic
analysis shows enzyme functionality to be mostly unchanged. Also, the role of pI
and ionic strength within the encapsulation environment was found to strongly
influence encapsulation. These results suggest that the electrostatic
manipulation of a strong supramolecular silica-precipitating complex of enzyme
and dendrimer has the potential of adding a vast array of chemical and biological
activity to hybrid materials. [image: see text] Enzyme immobilization within a
silica nanocomposite.
PMID- 17039577
TI - Amphiphilic poly(D,L-lactic acid)/poly(ethylene glycol)/poly(D,L-lactic acid)
nanogels for controlled release of hydrophobic drugs.
AB - Photocrosslinked nanogels with a hydrophobic core and hydrophilic shell are
successfully fabricated with the goal of obtaining a biocompatible and
biodegradable drug carrier for hydrophobic anticancer drugs. These nanogels are
composed of amphiphilic triblock copolymers, poly(D,L-lactic acid)/poly(ethylene
glycol)/poly(D,L-lactic acid) (PLA-PEG-PLA), with acrylated groups at the end of
the PLA segments. The copolymers are synthesized by ring-opening polymerization
and possess a low CMC (49.6 mg x L(-1)), which easily helps to form micelles by
self-assembly. The acrylated end groups allow the micelles to be photocrosslinked
by ultraviolet irradiation, which turn the micelles into nanogels. These nanogels
exhibit excellent stability as a suspension in aqueous media at ambient
temperature as compared to the micelles. Moreover, the size of the nanogels is
easily manipulated in a range of 150 to 250 nm by changing the concentration of
crosslinkers, e.g., ethylene glycol dimethacrylate, and ultraviolet light
irradiation time. The nanogels achieve a high encapsulation efficiency and offer
a steady and long-term release mechanism for the hydrophobic anticancer drug,
CPT. It shows that these nanogels are useful for a hydrophobic anticancer drug
carrier system. [pictures: see text] Formation of the PLA-PEG-PLA nanogels.
PMID- 17039578
TI - Synthesis of fluorinated chitin derivatives via enzymatic polymerization.
AB - Synthesis of fluorinated chitin derivatives has been achieved using chitinase
from Bacillus sp. as a catalyst. 6'-Fluoro- (1a), 6-fluoro- (1b) and 6,6'
difluoro- (1c) chitobiose oxazoline derivatives were newly prepared as TSAS
monomers for chitinase. Ring-opening polyaddition of these monomers proceeded
effectively at pH 8.0-9.0 and 30-40 degrees C, giving rise to alternatingly 6
fluorinated chitin derivatives (2a and 2b) from 1a and 1b, and fully 6
fluorinated chitin derivative (2c) from 1c under total control of
regioselectivity and stereochemistry. XRD measurements revealed that
polysaccharides 2a and 2b had crystalline structures similar to that of alpha
chitin. [reaction: see text]
PMID- 17039579
TI - Application of liquid chromatography/quadrupole time-of-flight mass spectrometry
(LC-QqTOF-MS) in the environmental analysis.
AB - This paper gives an overview of the potentials of liquid chromatography-hybrid
quadrupole time-of-flight mass spectrometry (LC-QqTOF) in the environmental
analysis. Examples of applications of QqTOF instruments for target analysis of
pharmaceuticals and pesticides are presented and discussed, as well as
applications aimed on the identification of unknown compounds present in
environmental waters or on the elucidation of structures of biodegradation and
photodegradation products. Specific issues such as uncertainty of mass
measurement and quantitative performances are discussed in details.
PMID- 17039581
TI - Towards the control and inhibition of glycation-the role of the guanidine
reaction center with aldehydic and diketonic dicarbonyls. A mass spectrometry
study.
AB - Glycation of proteins by glucose and formation of end-stage adducts (AGEs,
advanced glycation end products) has been implicated in pathological mechanisms
associated with diabetic complications, macrovascular disease, chronic and renal
insufficiency, Alzheimer's disease, and aging. Of the carbonyl containing
compounds involved in this process, alpha-dicarbonyls have particular importance,
being established as direct intermediates in the formation of well-known AGEs.
The guanidino group, present in arginine residues, suffers direct modifications
by sugars and its derivatives, and is considered to be an important chemical
basis, targeting the control and inhibition of glycation. Seven dicarbonyl
compounds, aldehydic and diketonic, were reacted with guanidine, in an attempt to
establish structure/activity relationships. Electrospray mass spectrometry,
together with tandem mass spectrometry, was used to identify and characterize the
reaction products. The reactivity of guanidine was found to vary with the
dicarbonyls used. For glyoxal, a high amount of dihydroxyimidazolidine was
formed, whereas for methylglyoxal, dihydroxyimidazolidine was slowly converted
into hydroimidazolone. Interestingly, aqueous guanidine was found to prevent
argpyrimidine formation. The formation of several amine-dicarbonyl moieties was
observed for the larger alkyl-diketonic dicarbonyls reaction systems, in
particular. Molecular structures, bearing a polar chain, of an imidazole ring,
and a nonpolar one, of alkyl groups, located at both sides of the imidazole
rings, were attributed to these moieties. Gas-phase experiments suggested that
the larger alkyl groups have a preference for being located at one of the sides
of the imidazole rings. Moreover, the referred amine-dicarbonyl moieties are
formed via (dihydroxyimidazolidine - 2H2O) moieties. The latter
(dihydroxyimidazolidine - 2H2O) moieties are formed in high amounts in the larger
alkyl-diketonic dicarbonyl reactions. Since these moieties react with dicarbonyl
molecules, and react even faster with already modified amine functions, we can
foresee that these species may be useful for controlling and inhibiting glycation
of larger biomolecules, such as proteins.
PMID- 17039582
TI - Coming home.
PMID- 17039583
TI - CR2/346--A baby with stridor.
PMID- 17039584
TI - CR4/112--Congenital isolated tracheal stenosis with organoaxial gastric volvulus.
PMID- 17039585
TI - CR6/30--A rare case of cyanosis in a child: almost a misleading diagnosis.
PMID- 17039586
TI - CR7/102--Left colonic perforation as the initial presentation of CF disease in
the neonatal period.
PMID- 17039587
TI - CR9/344--Case of disseminated BCG infection.
PMID- 17039588
TI - CR11/223--Imaging of obstructive sleep-apnea: report of a case.
PMID- 17039589
TI - [A rice resistant to the floods].
PMID- 17039590
TI - CD4 count most cost-effective.
PMID- 17039591
TI - More focus on prevention and research.
PMID- 17039592
TI - Gates talks about uncomfortable leaders.
PMID- 17039594
TI - [Poison control center at the H:S Bispebjerg Hospital open for the public].
PMID- 17039593
TI - Present and future approaches to Parkinson disease: from molecular insights to
new therapeutic avenues.
PMID- 17039595
TI - [Wrong citation--correction and a comment].
PMID- 17039596
TI - [No comments].
PMID- 17039597
TI - [Antihypertensive agents and apoplexy].
PMID- 17039598
TI - [Acupuncture therapy of low back pain 2].
PMID- 17039599
TI - [Frequencies use facilitates the interpretation of diagnostic results].
PMID- 17039600
TI - [Press, ethics and genetic screening].
PMID- 17039601
TI - Warning about postgrooming furunculosis.
PMID- 17039604
TI - Comparison does not compute.
PMID- 17039602
TI - A group M consensus envelope glycoprotein induces antibodies that neutralize
subsets of subtype B and C HIV-1 primary viruses.
AB - HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts
of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced
potent and broadly neutralizing antibodies against subtype C primary isolates. We
have used a centralized gene strategy to address HIV-1 diversity and generated a
group M consensus envelope gene with shortened consensus variable loops (CON-S)
for comparative studies with wild-type (WT) Env immunogens. Our results indicate
that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing
antibodies of similar or greater breadth and titer than the WT Envs tested,
indicating the utility of a centralized gene strategy. Our study also shows the
feasibility of iterative improvements in Env immunogenicity by rational design of
centralized genes.
PMID- 17039605
TI - Patient care. You look marvelous.
PMID- 17039603
TI - Attacks on amalgam raise moral, ethical questions.
PMID- 17039606
TI - Technology. The bidding begins.
PMID- 17039607
TI - [Physicians and scientific research: slight decline of the numbers of physicians
with a doctoral degree].
PMID- 17039609
TI - Alternative milks not suitable for allergic children.
PMID- 17039608
TI - 'Special' plans for CMS. HHS to keep tabs on physician-owned hospitals.
PMID- 17039610
TI - Sources that support the fluoridation of community water supplies is indeed
impressive.
PMID- 17039611
TI - Oral pathology quiz #52. Case numner 2. Vascular leiomyoma.
PMID- 17039612
TI - Oral pathology quiz #52. Case number 3. Ameloblastoma.
PMID- 17039613
TI - Oral pathology quiz #52. Case number 4. Odontogenic myxoma.
PMID- 17039614
TI - Illinois steps into HRDI probe. Attorney general issues subpoenas regarding think
tank.
PMID- 17039615
TI - Weight lifting in the human brain.
PMID- 17039616
TI - Taking on P4P, gain-sharing.
PMID- 17039617
TI - Recurrent worries. When anxieties interfere with life.
PMID- 17039618
TI - Pandemic flu. What you need to know.
PMID- 17039619
TI - Healthy eating. One-pot meals. A way to welcome fall.
PMID- 17039620
TI - A good night's sleep. Sleep loss can affect not only your quality of life, but
your health as well.
PMID- 17039622
TI - Who'll watch the kids? Even the most devoted parents need time away from their
children. Here the experts help you find a sitter you can trust.
PMID- 17039621
TI - Peak performance.
AB - Earlier this year, a Pittsburgh-based adventurer became the first American with
diabetes to reach the top of Mount Everest. He proved that nothing--not record
breaking winds, freezing temperatures, dangerous ice, or his disease--would slow
him down.
PMID- 17039623
TI - Autumn harvest. Whether sliced, roasted, or pureed, fall vegetables offer many
ways to welcome in this beautiful season.
PMID- 17039624
TI - Outbreak news. Acute watery diarrhoeal syndrome, Ethiopia.
PMID- 17039625
TI - Outbreak news. Botulism, Canada and United States.
PMID- 17039626
TI - Recommended composition of influenza virus vaccines for use in the 2007 influenza
season.
PMID- 17039627
TI - Paradoxes of abortion and prenatal injury.
PMID- 17039628
TI - The reversal test: eliminating status quo bias in applied ethics.
PMID- 17039629
TI - Bone void filler in posterior iliac crest reconstruction and to supplement
intertransverse process fusion.
PMID- 17039630
TI - Gender and ethics committees: where's the 'different voice'?
AB - Prominent international and national ethics commissions such as the UNESCO
International Bioethics Committee rarely achieve anything remotely resembling
gender equality, although local research and ethics committees are somewhat more
egalitarian. Under-representation of women is particularly troubling when the
subject matter of modern bioethics so disproportionately concerns women's bodies,
and when such committees claim to derive 'universal' standards. Are women missing
from many ethics committees because of relatively straightforward, if
discriminatory, demographic factors? Or are the methods of analysis and styles of
ethics to which these bodies are committed somehow 'anti-female'? It has been
argued, for example, that there is a 'different voice' in ethical reasoning, not
confined to women but more representative of female experience. Similarly, some
feminist writers, such as Evelyn Fox Keller and Donna Haraway, have asked
difficult epistemological questions about the dominant 'masculine paradigm' in
science. Perhaps the dominant paradigm in ethics committee deliberation is
similarly gendered? This article provides a preliminary survey of women's
representation on ethics committees in eastern and western Europe, a critical
analysis of the supposed 'masculinism' of the principlist approach, and a case
example in which a 'different voice' did indeed make a difference.
PMID- 17039631
TI - Safety, identity and consent: a limited defense of reproductive human cloning.
AB - Some opponents of reproductive human cloning have argued that, because of its
experimental nature, any attempt to create a child by way of cloning would risk
serious birth defects or genetic abnormalities and would therefore be immoral.
Some versions of this argument appeal to the consent of the person to be
conceived in this way. In particular, they assume that if an experimental
reproductive technology has not yet been shown to be safe, then, before we use
it, we are morally obligated to get either the actual consent or the presumed
consent of the person to be conceived. In this article, I attempt to explain the
appeal of such consent-based arguments as deriving from a mistaken view of
personal identity. I then argue that since this view is false, such arguments are
unsound. Finally, I argue that even if reproductive cloning is unsafe, it may
still be morally permissible in some circumstances.
PMID- 17039632
TI - Moral considerations in body donation for scientific research: a unique look at
the University of Tennessee's anthropological research facility.
AB - This paper discusses keys to the moral procurement, treatment and disposition of
remains used for scientific research, specifically those donated to the
University of Tennessee's Anthropological Research Facility (ARF). The ARF is an
outdoor laboratory dedicated to better understanding the fate of human remains in
forensic contexts, and focuses its research on decomposition, time since death
estimates, body location and recovery techniques, and skeletal analysis.
Historically, many donations were unclaimed bodies received from medical
examiners (although it will be shown that this trend is changing), and it has
been argued that the use of the unclaimed bodies for medical or scientific
purposes is a violation of autonomy since no consent was given by the individual.
It is argued here, however, that the domain of autonomous choice extends to one's
own corpse only insofar as expressed wishes are made known prior to one's death,
and that in the absence of expressed intent toward final disposition, it is
acceptable for institutions to receive donations from medical examiners or family
members. This paper also discusses other philosophical issues related to
donation, consent and autonomy, and the forensic benefits of research conducted
at the Anthropological Research Facility.
PMID- 17039633
TI - Speeding up cancer-drug development.
PMID- 17039634
TI - Appraisal of bevacizumab and cetuximab for treatment of metastatic colorectal
cancer in the UK.
PMID- 17039635
TI - When DNA means 'do not attempt'.
PMID- 17039637
TI - Eyeglasses: score spectacular savings.
PMID- 17039636
TI - Bagged salads: the yuck factor.
PMID- 17039638
TI - Generic drugs: shop around for the best deals.
PMID- 17039640
TI - Acupuncture was better than no acupuncture but did not differ from minimal (sham)
acupuncture for chronic low back pain at 8 weeks.
PMID- 17039639
TI - Evaluation of studies of treatment harm.
PMID- 17039641
TI - Medicare physician payments and spending.
AB - The Medicare program's physician payment method is intended to control spending
while ensuring beneficiary access to physician services, but there are signs that
it may not be working. The physician's role in the health care delivery system as
the primary source of information and treatment options, together with growing
demand for services and the imperfect state of knowledge about appropriate
service use, challenge Medicare's ability to achieve these two goals. This issue
brief describes the history of physician spending and the contribution of
escalating service use and intensity of services to the rise in Medicare outlays,
setting the stage for further discussion about the use of the Medicare payment
system to control spending and ensure access.
PMID- 17039642
TI - [Acute cerebral symptoms in elderly women].
PMID- 17039643
TI - [All cases of stroke has a cause].
PMID- 17039644
TI - A real head scratcher. Schools are struggling with how best to handle lice.
PMID- 17039645
TI - Vanished behind the counter. Starting this week, you'll need help buying your
claritin and nyquil.
PMID- 17039646
TI - Behind the baby count.
PMID- 17039647
TI - Taste comparison of corticosteroid suspensions.
AB - OBJECTIVE: Although numerous taste studies have compared the palatability of
antibiotic suspensions, few have compared the palatability of corticosteroid
suspensions. Therefore, we compared the taste of 8 commonly prescribed liquid
corticosteroid suspensions with the intent to help guide prescribing practices
and improve patient compliance. METHODS: We conducted a randomized, double-blind
study using 31 adult volunteers ages 24 to 57. All volunteers were asked to
sample 8 different pediatric corticosteroid suspensions and to rate the
palatability of their taste and aftertaste. The mean scores for each sample were
then compared. RESULTS: The 8 suspensions fell into 2 groups based on their taste
scores: one group with relatively high scores or more acceptable tastes (Orapred,
Pediapred, and a dexamethasone suspension) and a second group with relatively low
scores or less acceptable tastes (a prednisone suspension and 4 cherry-flavored
prednisolone suspensions). CONCLUSIONS: The results demonstrate a significant
difference in palatability between corticosteroid suspensions. Not only will this
new information help clinicians choose between otherwise equivalent
corticosteroid suspensions but, given the importance children place on taste, may
improve compliance as well.
PMID- 17039648
TI - Successful treatment of hand and foot psoriasis with efalizumab therapy.
AB - Hand and foot psoriasis can appear in a plaque-type or pustular-type form. Any
form of psoriasis that occurs on the hands and feet can have a debilitating
effect on the patient's daily functions. Here we present a case series of
patients with plaqueor pustular-type hand and foot psoriasis whose conditions
were successfully managed with the biologic agent efalizumab. In many of these
patients, the disease was refractory to multiple systemic psoriasis treatments.
Treatment with efalizumab was effective and well-tolerated, with few adverse
events. Many of the patients described here reported an improvement in both their
physical functioning and health-related quality of life. The efficacy of
efalizumab in treating these cases of hand and foot psoriasis suggests that it
may provide therapeutic benefit.
PMID- 17039649
TI - Hereditary angioedema.
AB - Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by a C1
inhibitor deficiency. It is characterized by potentially life-threatening
recurrent episodes of angioedema of the skin and mucosa. Several recent studies
have further elucidated the immunology of HAE implicating bradykinin, the key
mediator of the contact system. This article reviews the pathophysiology,
subtypes, and clinical features of HAE. Therapeutic approaches for various
clinical situations (emergency and prophylactic regimens) are also discussed.
PMID- 17039650
TI - Topical diphenylcyclopropenone as a measure of immune competence in HIV
seropositive subjects.
AB - BACKGROUND: CD4 T cell counts are recognized as the standard method for
monitoring HIV-seropositive patients and, along with viral load, are clinically
important as indicators for initiating highly active antiretrovival therapy
(HAART). Skin reaction scores following topical application of
diphenylcyclopropenone (DPC) also demonstrate diagnostic utility as a functional
measure of immune competence. METHODS: We used low sensitizing doses of DPC in 40
patients applied in a non-volatile, non-irritating topical delivery system to
assess immune competence in 40 HIV-seropositive subjects with a range of CD4 T
cell counts. Standardized patch test reading scores were used, with 2+ or greater
scores (erythema and induration) indicative of a positive response. The patch
test scores were then compared with CD4 counts. RESULTS: Application of DPC in
concentrations of 0.4% and 0.2% successfully resulted in 90% sensitivity skin
reaction scores in subjects with >300 CD4 T cells/microL, following a single 0.1
mL application to the inner aspect of the arm. Lower DPC concentrations of 0.1%
and 0.05% were too low for initial sensitization reactions. Three subjects with
CD4 counts between 150 and 300 cells/microL showed positive skin reactions
indicating that this DPC test gives the clinician information on cellular
immunity beyond the CD4 count. CONCLUSION: We conclude that a single topical
application of DPC at concentrations between 0.2% and 0.4% can serve as a measure
of immune competence in HIV-seropositive patients. As a functional measure of
immunocompetence, this DPC test provides information beyond a CD4 count, which is
particularly relevant to HIV-positive subjects with CD4 counts between 200 and
350 cells/microL.
PMID- 17039651
TI - A novel vaccine (Zostavax) to prevent herpes zoster and postherpetic neuralgia.
AB - Varicella-zoster virus is the causal agent of varicella and herpes zoster in
humans. Herpes zoster results from reactivation of latent varicella-zoster virus
(VZV) within the sensory ganglia. The incidence and severity of herpes zoster
increase with advancing age. More than half of all persons in whom herpes zoster
develops are older than 60 years. The most frequent debilitating complication is
postherpetic neuralgia, a neuropathic pain syndrome that persists or develops
after the dermatomal rash has healed and can be prolonged and disabling. There
are many limitations of current therapies for herpes zoster and postherpetic
neuralgia. A live attenuated VZV vaccine has been developed and recently approved
by the FDA for the prevention of herpes zoster in individuals 60 years of age and
older. In a randomized, double-blind, placebo-controlled trial with 38,546
patients 60 years of age or older, the use of the zoster vaccine reduced the
burden of illness due to herpes zoster by 61.1% (P < .001), reduced the incidence
of postherpetic neuralgia by 66.5% (P < .001), and reduced the incidence of
herpes zoster by 51.3% (P < .001). In this review, we will discuss the history of
the use of the varicella vaccine in children, and the subsequent development of
the new zoster vaccine.
PMID- 17039652
TI - Inhibition of propionibacterium acnes by bacteriocin-like inhibitory substances
(BLIS) produced by Streptococcus salivarius.
AB - We report the in vitro inhibition of Propionibacterium acnes (P. acnes) by a
bacteriocin-like inhibitory substance (BLIS-like substance) produced by
Streptococcus salivarius (S. salivarius). Bacteriocins are proteinaceous
substances produced by bacteria that are capable of inhibiting the growth of
similar bacterial strains. Unlike classical antibiotics, they have a relatively
narrow spectrum of killing activity, resulting in a reduction in the intensity of
selection for resistance. These findings suggest that BLIS may potentially be
used for its anti-P. acnes activity in the treatment of acne.
PMID- 17039653
TI - A protocol for facial volume restoration with poly-L-lactic acid.
AB - Poly-L-lactic acid is a biodegradable synthetic polymer used in an injectable
form for subcutaneous volume restoration. Volumetric correction following
subcutaneous and deep dermal injection of poly-L-lactic acid is thought to occur
through a foreign body tissue response leading to increased production of
fibroblasts and subsequent neocollagenesis. Despite the growing popularity and
use of this material, there has been a scarcity of published information
describing proper injection technique, and many practitioners remain unfamiliar
with its use. Appropriate injection technique is critical since incorrect
placement of the material can lead to long-lasting unintended results. We present
a protocol for successful injection of poly-L-lactic acid into the submalar and
buccal regions.
PMID- 17039654
TI - Oral isotretinoin for acne, adjusting treatment according to patient's response.
AB - BACKGROUND: Oral isotretinoin is an established effective therapy for acne. No
published data is available on the efficacy and side effects of this drug in
Iranian patients. PATIENTS AND METHODS: A total of 132 acne patients with a mean
age of 22.9 +/- 6.2 years were treated with oral isotretinoin (Roaccutane) and
followed-up from 1999 through 2005. Each patient was started with a dose of 0.75
mg/kg per day until all active lesions healed, followed by a maintenance dose of
20 mg/kg per day for one more month. Laboratory tests were done at monthly
intervals. Evaluation of clinical response was based on Leeds technique. Patients
were followed-up for a mean period of 4.4 years. RESULTS: Most of the patients
had severe nodulocystic acne involving both trunk and face. Treatment was
continued for 6.6 +/- 2.5 months with a cumulative dose of 111.5 mg/kg +/- 33.9.
The mean final improvement rate was 96.7% (95% CI, 84.9% to 108.5%). There was no
correlation between improvement rate and age, sex, duration of acne, length of
treatment, or cumulative dose. Side effects were generally mild and treated
conservatively. In the follow-up, period 18.35% experienced relapse after a mean
interval of 1.28 years, 9.17% required a second course of isotretinoin, and only
one case needed 3 courses of treatment. CONCLUSION: Isotretinoin is an effective
and safe treatment for acne in Iranian patients. Starting treatment with a high
dose and modifying the length of treatment based on the therapeutic response in
each patient, might lead to a rapid and good response rate with minimal side
effects.
PMID- 17039656
TI - Induction of lesional and circulating leukocyte apoptosis by infliximab in a
patient with moderate to severe psoriasis.
AB - Infliximab demonstrates high efficacy in treating psoriasis in a high proportion
of patients. In this report we demonstrate induction of plaque (T cells,
dendritic cells) and peripheral blood (T cells, monocytes) leukocyte apoptosis
following a single infliximab infusion in a psoriasis patient.
PMID- 17039655
TI - Comparison of metformin versus rosiglitazone in patients with Acanthosis
nigricans: a pilot study.
AB - BACKGROUND: Acanthosis nigricans (AN) is a skin condition commonly present on the
neck of obese subjects. Obesity is often accompanied by insulin resistance and/or
hyperinsulinemia. Metformin and rosiglitazone are 2 pharmacologic agents useful
in conditions characterized by insulin resistance. OBJECTIVE: The aim of our
study was to compare the efficacy of metformin versus rosiglitazone on AN lesions
of the neck as well as their effects on metabolic and anthropometric variables.
METHODS: This 12-week randomized, open-label pilot study involved overweight or
obese subjects with AN treat with either metformin (n=4) or rosiglitazone (n=3).
RESULTS: Only the rosiglitazone group showed a significant reduction in insulin
levels. No effect on the severity of AN was observed, but modest improvements of
skin texture occurred in both treatment groups. CONCLUSIONS: Metformin and
rosiglitazone were well-tolerated. Although efficacy on skin lesions was very
modest, their use in acanthotic subjects might be useful during longer treatment
periods.
PMID- 17039657
TI - Etanercept therapy for silicone granuloma.
AB - A patient developed a typical, painful, and debilitating reaction on the thighs
following injection of ostensibly medical grade "silicone" to achieve alteration
of body contours. The refractory silicone granuloma responded dramatically to
treatment with etanercept.
PMID- 17039658
TI - An intertrigo-like eruption from pegylated liposomal doxorubicin.
AB - Pegylated liposomal doxorubicin (PLD) is a chemotherapeutic agent used in the
treatment of solid tumors. It has a considerably lower risk of cardiotoxicity
than its parent compound, doxorubicin. PLD also has a different cutaneous side
effect profile than doxorubicin, and its cutaneous toxicity can be dose limiting.
We report the case of a 60-year-old woman who developed erythema and erosions in
the axilla and groin while on PLD for breast cancer. Nystatin was ineffective.
Biopsies revealed an interface dermatitis with epidermal dysmaturation. Bland
emollients and reduction in the dose of PLD resulted in resolution of the
eruption. An intertriginous eruption with histological features of epidermal
dysmaturation and an interface dermatitis has been previously reported in the
dermatopathology literature. This eruption appears to be a distinct cutaneous
toxicity of PLD.
PMID- 17039659
TI - Etanercept responsive acrodermatitis continua of Hallopeau: is a pattern
developing?
AB - Acrodermatitis continua of Hallopeau (ACH) is a rare disease. Little is known
about its etiology or relative effectiveness of the various therapeutic
approaches. However, in the literature a pattern seems to be developing on
successfully treated patients using biologic therapies. Here, we further
emphasize the potential breakthrough presented by the novel immune based
therapies. This report consists of a case of etanercept responsive ACH along with
a brief review of the literature.
PMID- 17039660
TI - Successful treatment of patch type mycosis fungoides with tacrolimus ointment
0.1%.
AB - Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of
lymphoproliferative disorders caused by clonally-derived, skin-invasive T cells.
A variety of skin-directed and systemic therapies are available to treat mycosis
fungoides/Sezary syndrome (MF/SS), the therapeutic choices of which are guided by
the stage of disease. A 29-year-old man presented at our clinic with pruritic,
erythematous macules located on the sternum and the lower back. Histological
findings and immunohistochemistry studies showed patch stage MF. The patient was
treated with tacrolimus ointment 0.1% twice daily for one month, achieving
complete remission. Three months after the first episode a relapse was
successfully treated with the same therapeutic regimen. Tacrolimus is an
immunomodulatory macrolide that reduces the stimulatory capacity toward T cells
and is therefore worth investigating as a treatment of CTCL. Topical tacrolimus
has been related to an unknown effect with the risk for secondary malignancies
including CTCL. Also, black box warnings have been proposed by the FDA for the
topical calcineurin inhibitors. Nevertheless, our results in the treatment of
early stage MF are in agreement with other unpublished data that have observed
its efficacy. To our knowledge, there is no other case of patch type mycosis
fungoides treated with tacrolimus ointment 0.1% in the medical literature.
PMID- 17039661
TI - Wells syndrome: an enigmatic and therapeutically challenging disease.
AB - Wells syndrome, also known as eosinophilic cellulitis, is an uncommon condition
whose etiology often remains a mystery. Patients present with recurrent cutaneous
swellings that are often cellulitic in appearance. Histopathologic evaluation of
the skin lesions reveals a dense dermal eosinophilic infiltrate, marked edema,
and characteristic "flame figures". Notably, the picture is devoid of vasculitis.
Therapy with low-dose systemic steroids has proven variably successful. Clinical
evidence lending support for the efficacy of other medications has been, for the
most part, anecdotal. We present a case of Wells syndrome, review the literature,
and discuss therapeutic options.
PMID- 17039662
TI - Schools of pharmacology: retinoid update.
AB - The most widely used retinoids include topical tretinoin (Retin-A), adapalene
(Differin), topical tazarotene (Tazorac), isotretinoin (Accutane), and acitretin
(Soriatane). This article will review new uses and developments in tazarotene
(its failure to secure FDA approval in oral form for psoriasis), adapalene (its
new 0.3% gel form and use in rosacea), alitretinoin (its use in photoaging),
bexarotene (its use for psoriasis and chronic hand dermatitis), isotretinoin (the
IPledge program, its use for neuroblastoma and branded formulation
pharmacological superiority to generics), and retinoic acid metabolism-blocking
agents (RAMBAs) (liarazole use for ichthyosis and psoriasis).
PMID- 17039663
TI - Contact dermatitis: a practice parameter.
PMID- 17039664
TI - Change in the pattern of IgE reactivity to timothy grass and birch pollen
allergens over a 20-year period.
AB - BACKGROUND: Several studies have shown that the prevalence of allergy and
allergen sensitization has increased in recent years. However, the changes in the
pattern of IgE reactivity to individual allergens are mostly unknown. OBJECTIVE:
The aim of this preliminary study was to assess the change in IgE reactivity
profile to individual timothy grass and/or birch pollen allergens in sera from
sensitized individuals randomly collected 20 years apart. METHODS: Serum samples
from 51 sensitized individuals were obtained from 2 cross-sectional surveys
performed in 1973 and 1994 using random samples from Vammala, Finland. The sera
were analyzed for IgE reactivity to timothy grass and/or birch pollen extracts,
recombinant (r)Phl p 1, 2, 5, 6, 7, 11, 12, native (n)Phl p 4, and rBet v 1, 2
and 4 by immunoassay (ImmunoCAP). RESULTS: The median (range) concentrations of
IgE antibodies to timothy grass and birch pollen were higher in 1994 than in 1973
(6.47 [0.35 to >100] kU A/L vs 1.53 [0.40-25.3] kU A/L; P=.0035). The prevalence
of IgE reactivity to some allergens was higher in 1994 than in 1973, particularly
rPhl p 5 (52% vs 19%), rPhl p 6 (43% vs 12%), and rBet v 1 (100% vs 29%). There
was a correlation between timothy grass pollen-specific serum IgE levels and the
numbers of IgE reactivities to individual allergens (p=0.76, P<.001).
CONCLUSIONS: The increase in specific IgE levels together with a possible
increase in the prevalence of IgE reactivity to the major allergens Phl p 5 and
Bet v 1 between 1973 and 1994 may have contributed to the increase in atopic
conditions in Finland.
PMID- 17039665
TI - Variability of Alt a 1 expression by different strains of Alternaria alternata.
AB - BACKGROUND: While it is well known that there is significant intraspecific
variation in the content an potency of Alternaria alternata allergens, little
data has been published on intraspecific variability for individual allergens
from moulds. OBJECTIVE: To assess the variability of Alt a 1 expression in
different strains of A alternata. METHODS: Eleven strains of A alternata were
cultured in a Czapek broth medium and culture filtrate extracts were obtained. A
sensitive two-site enzyme-linked immunosorbent assay was used to measure Alt a 1
concentrations in medium following 3 weeks of culture and in culture filtrate
extracts. RESULTS: Expression of Alt a 1 was highly variable in different strains
ofA alternata (coefficient of variation > 135%). A good correlation was found
between Alt a 1 concentrations at the beginning of the process and measurements
at the end of extract production (r=0.940). CONCLUSIONS: The high variability of
Alt a 1 expression in different A alternata strains makes it necessary to measure
Alt a 1 concentrations during the first stage of allergenic extract production in
order to be able to choose a suitable strain for producing extracts or purifying
Alt a 1.
PMID- 17039666
TI - Clinical effects of apple polyphenols on persistent allergic rhinitis: A
randomized double-blind placebo-controlled parallel arm study.
AB - BACKGROUND: We often encounter persistent allergic rhinitis due to house dust
mites in the practice of otolaryngology, and its prevalence in Japan is high
(18.7%). Persistent allergic rhinitis is usually treated with antihistamines and
local steroids, but they often cause adverse effects such as sedation and
drowsiness. Polyphenols derived from apples have been reported to suppress
histamine release from rat cells, reduce auricular swelling in allergic mice, and
alleviate skin inflammation in atopic patients. These effects suggest that apple
polyphenols are effective for the treatment of various allergic disorders, but
the results of their clinical use have not been reported. OBJECTIVE: To assess
the effect of drinks containing apple polyphenols on clinical symptoms of
persistent allergic rhinitis. METHODS: Thirty-three patients aged 15 to 65 years
with moderate or severe persistent allergic rhinitis in whom the symptoms
persisted for 3 years or longer were treated without apple polyphenols (control
group), with a low dose of apple polyphenols, or with a high dose of apple
polyphenols, and changes in the clinical symptoms were examined. RESULTS:
Significant improvements were observed in sneezing attacks (P<.05) and nasal
discharge (P<.01) in the high-dose group and in sneezing attacks (P<.05) in the
low-dose group. Compared with the control group, an improvement was observed in
sneezing attacks and nasal discharge in many patients of the polyphenol-treated
groups. In terms of intranasal findings, a significant improvement was observed
in swelling of the nasal turbinate in the low-dose group (P<.05). The percentage
of patients who showed an improvement in swelling of the nasal turbinate was
higher in the polyphenol-treated groups. CONCLUSIONS: We conclude that apple
polyphenols are effective in alleviating symptoms of persistent allergic
rhinitis.
PMID- 17039667
TI - Prevalence of asthma and allergic diseases in Sanliurfa, Turkey, and the relation
to environmental and socioeconomic factors: is the hygiene hypothesis enough?
AB - BACKGROUND: The prevalence of asthma and allergic diseases has been reported to
be higher in urban than in rural areas between developed and underdeveloped
countries and within any given country. Studies in Turkey have yielded different
results for different regions. This study aimed to investigate the prevalence of
asthma and atopy in Sanliurfa, Turkey, and the influence of environmental
factors. MATERIALS AND METHODS: We recruited 1108 children from different areas
of Sanliurfa and administered the questionnaire of the International Study of
Asthma and Allergies in Childhood. Items asking for socioeconomic data were also
included. Skin prick and purified protein derivative tests were performed on the
children. Measles antibodies were determined and feces were analyzed for
parasites. RESULTS: The total prevalence of atopic diseases was 8.6% (n =
95/1108), asthma 1.9% (n=21/1108), allergic rhinitis 2.9% (n=32/1108), and
allergic conjunctivitis 3.8% (n=42/1108). The rate of atopic diseases was 5.6%
(n=32/573) in children attending schools in peripheral, less urban, slum areas
while it was 11.8% (n=63/535) in those attending city-center schools (OR, 2.2;
95% confidence interval [CI]; 1.4-3.5; P<.001). Skin prick test positivity was
observed in 3.9% (n=43/1108) overall; at schools in slum areas it was 1.9%
(n=11/573), whereas at central schools the rate was 6% (n=32/535) (OR, 4.08; 95%
CI, 2.03-8.20; P<.001). The prevalence of asthma and atopic diseases was
significantly higher in children who have a family history of atopy, attend a
central school, live in an apartment, have more rooms in their homes, and enjoy
better economic conditions. CONCLUSION: We found associations between various
factors suggested by the hygiene hypothesis and asthma, and very low rates of
prevalence of asthma and atopic diseases both in Sanliurfa in comparison with the
more developed western regions and in the peripheral slum areas. The hygiene
hypothesis is helpful in explaining these observations.
PMID- 17039668
TI - IgE cross reactivity between reindeer and bovine milk beta-lactoglobulins in
cow's milk allergic patients.
AB - BACKGROUND: Allergic reactions to cow's milk are common in small children. One of
the main protein allergens found in cow's milk is beta-lactoglobulin (beta-Lg).
Reindeer and bovine milk both contain related beta-Lg proteins, but the
allergenicity of reindeer beta-Lg has not previously been studied. The purpose of
this study was to analyze the immunological cross-reactivity of IgE antibodies
from children with cow's milk allergy to reindeer and bovine beta-Lg. METHODS:
Sera from 17 children and a serum pool of 4 patients with elevated cow's milk
specific IgE were investigated. Beta-Lg from bovine and reindeer milk was
isolated in native form and an enzyme-linked immunosorbent inhibition assay was
developed. Bovine beta-Lg was used as a capturing antigen and the inhibiting
effects of reindeer and bovine beta-Lg on the IgE binding were measured. RESULTS:
Cross-reactivity patterns of bovine milk beta-Lg specific IgE to reindeer beta-Lg
varied among patients. In general, reindeer beta-Lg showed significantly lower
inhibition (mean 43%) of IgE binding to the capturing antigen than did bovine
beta-Lg (mean 89%). In some patients, even high concentrations of reindeer beta
Lg only partly eliminated the IgE binding to bovine beta-Lg. CONCLUSIONS: The
partial cross-reactivity of human anti-bovine IgE with reindeer beta-Lg suggests
that it lacks important bovine epitopes and those that are recognized are only
weakly bound.
PMID- 17039669
TI - Changes in the expression of Fas on T lymphocytes after allogeneic fetal thymus
transplantation in systemic lupus erytematosus mice.
AB - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder that can
produce inflammation in many organ systems. The rate of spontaneous apoptosis in
lymphocytes from human SLE patients has been reported to be increased both in
vivo and in vitro. Studies of fetal thymus transplantation in an autoimmune
syndrome indicate that cellular immunity can be reconstituted and regulatory T
cell functions can be normalized. OBJECTIVES: The aim of this study was to assess
changes in Fas expression on T lymphocytes following fetal thymus transplant.
METHODS: (B/CxB6) F1 (H-2d/h) female F1 mice were assigned to groups designated
transplantation, normal, and control. Mice in the transplantation and control
groups received parental BALB/c lymphocytes intravenously. Thirty days after
injection of the lymphocytes, each F1 mouse in the transplantation group received
a fetal thymus graft under the right renal capsule. Mice in the control group did
not receive thymus transplant and mice in the normal group received neither
parental lymphocytes nor a fetal thymus graft. All mice received cyclosporin A at
2 mg/kg daily for the first 12 days after transplantation or starting on the
corresponding day. Thirty days after thymus transplantation, F1 mice were
sacrificed and expression of Fas in peripheral blood lymphocytes was analyzed by
flow cytometry. RESULTS: The percentage of CD4Fas+ T lymphocytes was
significantly increased in the control group and the transplantation group
compared with the normal group. Corresponding significant differences were
observed for CD8Fas+, CD4CD25Fas', and CD45RB(low)Fas+ T lymphocytes.
CONCLUSIONS: In this study, we found that fetal thymus transplantation had a
significant effect on the expression of Fas by T cell subtypes in SLE mice.
PMID- 17039670
TI - Tahini, a little known sesame-containing food, as an unexpected cause of severe
allergic reaction.
AB - We describe the case of a young woman with asthma and confirmed food allergy to
sesame who had 2 severe systemic reactions after the inadvertent ingestion of
tahini, a paste made with ground sesame seeds that is not generally known by
physicians and patients as a sesame-containing food. A double-blind placebo
controlled food challenge confirmed the allergy to tahini in our patient. As new
products and recipes are being introduced from around the world on a regular
basis, it is essential that at-risk patients are able to obtain information about
allergens used as ingredients and as potential contaminants. This should be
applied not only to packaged food but also to freshly made foods, such as those
served in restaurants.
PMID- 17039671
TI - Cross-reactivity among amide-type local anesthetics in a case of allergy to
mepivacaine.
AB - Among the various adverse reactions to local anesthetics, IgE-mediated reactions,
particularly to the more commonly used amide group, are extremely rare. We report
the case of a 39-year-old man who suffered itching and generalized urticaria with
facial angioedema 15 minutes after administration of mepivacaine. Skin tests
revealed a strong positive reaction to mepivacaine, lidocaine, and ropivacaine,
but negative reactions to bupivacaine and levobupivacaine. Furthermore, double
blind placebo-controlled subcutaneous challenge with bupivacaine and
levobupivacaine was well tolerated. We conclude that an extensive allergologic
study must be carried out in rare cases of true allergic reaction to amide-type
local anesthetics in order to rule out cross reactivity.
PMID- 17039672
TI - Human seminal plasma allergy and successful pregnancy.
AB - Human seminal plasma allergy in women is an uncommon phenomenon. A great variety
of reactions ranging from local swelling to generalized systemic reactions have
been described, and local symptoms have often been misdiagnosed as chronic
vulvovaginitis. Sperm barriers, such as condoms, are the most widely advocated
method for avoiding these reactions; however this is not acceptable to couples
who wish to have children. We present a case of a woman with human seminal plasma
allergy who became pregnant after a fourth cycle of artificial insemination.
Sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblotting showing
an IgE binding band at 28kDa in the husband's seminal fluid identified the
culprit allergen. Artificial insemination is an effective way to achieve a
pregnancy in patients with seminal plasma allergy.
PMID- 17039673
TI - Meloxicam-associated anaphylactic reaction.
AB - Anaphylactic reaction to meloxicam has never been reported to date. We report 2
cases of meloxicam-induced anaphylactic reaction with no sensitivity to another
selective cyclooxygenase 2 inhibitor. A thorough drug allergy work-up should be
done before other cyclooxygenase inhibitors are prescribed.
PMID- 17039674
TI - Drug neosensitization during anticonvulsant hypersensitivity syndrome.
AB - Anticonvulsant hypersensitivity syndrome (AHS) is a rare, severe drug
hypersensitivity reaction included in the drug-related rash with eosinophilia and
systemic symptoms syndrome (DRESS), in which a transient state of immune
suppression and reactivation of latent virus infections have been observed. We
describe 5 patients who developed neosensitization to different drugs taken
during a previous episode of anticonvulsant-related DRESS, in whom skin prick,
intradermal and/or patch tests were performed to confirm the diagnosis of drug
hypersensitivity. In 1 patient, transient hypogammaglobulinemia was observed
during the AHS. Four of the 5 patients developed a delayed skin eruption or a
delayed systemic hypersensitivity reaction after intake of a drug that they had
also taken during a previous anticonvulsant DRESS which had occurred months or
years earlier; in the fifth, a possible reaction was prevented thanks to the
allergy workup. The diagnosis of drug allergy was demonstrated by positive
delayed reaction to intradermal test with amoxicillin in 2 cases, positive patch
tests to paracetamol and amitriptyline in 2 cases, and by clinical evidence of
ceftriaxone erythroderma in one. The possibility of neosensitization to drugs
administered during anticonvulsant-related DRESS should be considered. A
transient state of immunosuppression induced during the anticonvulsant-related
DRESS may trigger latent virus reactivation and massive nonspecific immune system
response, which may lead to breakdown of tolerance to other drugs present at that
time in the organism.
PMID- 17039675
TI - Diagnosis and management of hypersensitivity reactions caused by oxaliplatin.
AB - Hypersensitivity reactions to oxaliplatin have been increasing since its
introduction at the end of the 1990s, but allergy tests with antineoplastic drugs
are rarely used to aid diagnosis. We describe 5 cases in which hypersensitivity
reactions to oxaliplatin after several courses of chemotherapy were managed by
allergy testing and desensitization. Skin prick tests were negative at 1 mg/mL in
all patients, positive at 10 mg/mL in 2 tested patients, and negative in 10
control subjects. Intradermal tests were positive and not irritant at 0.01 to
0.001 mg/mL concentrations. A desensitization protocol with increasing
concentrations and flow rates was successfully completed in all patients. We
conclude that prick and intradermal skin tests are useful in the diagnosis of
hypersensitivity reactions to oxaliplatin and that the desensitization protocol
performed avoided discontinuation of chemotherapy in all patients.
PMID- 17039676
TI - Treating sensitivity during tooth whitening.
AB - The most common side effect of tooth whitening is tooth sensitivity. There are a
number of materials and techniques for reducing sensitivity. This article focuses
on potassium nitrate applied either by brushing before initiating whitening or by
application via a tray during whitening to reduce sensitivity. A detailed step-by
step procedure for managing hypersensitive patients is described.
PMID- 17039677
TI - Managing the whitening process.
PMID- 17039678
TI - Validating the roles of apex locators and sonic instrumentation in root canal
therapy.
AB - Paramount to the success of endodontic therapy is determining the working length
of the canal and, subsequently, effectively cleaning and irrigating the canal.
Electronic apex locators and sonic instrumentation can help overcome some of the
clinical and practical challenges inherent in endodontic treatment. This article
reviews literature findings regarding the applications of apex locators and sonic
instrumentation to more accurately determine working length and enhance canal
preparation and irrigation. A clinical technique is presented for completing
canal preparation and irrigation using sonics.
PMID- 17039679
TI - Implant therapy using ultraspeed CO2 lasers.
AB - tial applications are very beneficial clinically. As the technology improves,
different wavelengths and laser mediums exhibit advantages and disadvantages in
those clinical applications. The purpose of this article is to discuss the use of
the CO2 UltraSpeed Laser for implant dentistry as well as how it compares, in the
author's opinion, to other soft tissue
PMID- 17039680
TI - The essence of restorative care: long-term tooth preservation.
AB - Adhesion dentistry and the development of advanced ceramic core materials have
truly revolutionized the potentials of restorative care. For years, the only
indirect alternatives were gold and porcelain-fused-to-metal restorations. Today
we are afforded many choices to customize our treatment. It is the intent of this
article to review current materials and impose new thought patterns on the
restorative aspects of vital and nonvital teeth.
PMID- 17039681
TI - An overview of OSHA training for dentistry.
PMID- 17039682
TI - OSHA--what is its role in dentistry and how do we provide training?
AB - The mission of the Occupational Safety and Health Administration (OSHA) is to
ensure the safety and health of America's workers. Although OSHA's focus is on
safety, there is a natural overlap into the infection control arena. The work
practice control, engineering control, and personal protective equipment
regulations are examples of OSHA safety topics that have a direct impact on
dental infection control. In a similar fashion, the regulations designed to
protect the dental health care worker often translate into increased safety for
the dental patient. To ensure their safety, OSHA requires workers to be
appropriately trained. This article reviews the regulatory significance of OSHA,
compares OSHA with other regulatory and advisory agencies, and discusses OSHA's
training requirements. Principles for conducting training in the dental health
care setting along with suggestions for assessing training also are presented.
PMID- 17039683
TI - OSHA safety requirements and the general duty clause.
AB - Dental offices and clinics are subject to the same general safety requirements as
other workplaces. Current guidelines, inspections, education, and training focus
on infectious disease as the major workplace hazard for dental health care
personnel (DHCP). However, the Occupational Safety and Health Administration has
cited an increasing variety and number of general safety hazards during
inspections of dental offices. A review of the general safety requirements for
personal protective equipment and fire safety as they relate to DHCP follows. The
authors discuss the responsibility of both employers and employees to perform
workplace hazard evaluation and to implement education, engineering controls, and
work practice controls to minimize their exposure to recognized and emerging
workplace hazards.
PMID- 17039684
TI - Staying in compliance with the Bloodborne Pathogens Standard.
AB - Safety and health programs must be annually reviewed and followed. This article
provides a systematic review of each component of the Bloodborne Pathogens
Standard and suggestions on how to incorporate the information into staff
training and routine practice.
PMID- 17039685
TI - Comprehensive training for hazard communication.
AB - Long before the Bloodborne Pathogens Standard caught the attention of the dental
profession, the Occupational Safety and Health Administration required all
employers to collect information about hazardous chemicals in the workplace and
provide information and training to employees regarding the materials. The Hazard
Communication Standard requires employers to establish written programs, collect
specific information regarding workplace chemicals, and conduct a formal training
program for employees.
PMID- 17039686
TI - Interview with Tony Kovner, Ph.D., professor, Wagner Graduate School of Public
Service, New York University.
PMID- 17039687
TI - The measurement conundrum.
PMID- 17039689
TI - Task overlap among primary care team members: an opportunity for system redesign?
AB - This article presents the results of research on a systematic approach to the
assignment of primary care work in the Veterans Health Administration. Based on a
functional job analysis protocol, the study identified overlap in the performance
of primary care tasks among multiple occupational groups as prima facie evidence
of opportunities to reallocate work responsibilities. Results show that
registered nurses, physicians, advanced practitioners, and licensed vocational
nurses reported performing 60 percent to 97 percent of the same tasks, while
clerks and health technicians appeared to be underutilized. The frequency and
duration with which occupational groups performed each task were also examined,
providing additional evidence to be used in improving clinic efficiency. The
management of healthcare personnel can be improved through systematic analysis of
the work, the worker, and the work organization and through more informed
decisions about the appropriateness of task assignment (or reassignment). This
article presents an evidence-based approach to personnel management with
important implications for clinic efficiency. The approach can be used to guide
strategic planning and staffing decisions by identifying not only who currently
does the work but, more importantly, who should be doing the work given the full
array of data.
PMID- 17039688
TI - Communication and relationship management.
PMID- 17039690
TI - Managing variation in demand: lessons from the UK National Health Service.
AB - Managers within the U.S. healthcare system are becoming more aware of the impact
of variation in demand on healthcare processes. The UK National Health Service
provides a prime example of a system that has experienced the consequences when
the issue is not dealt with satisfactorily, having suffered from excessive queues
for a prolonged period. These delays are mostly caused by a lack of attention to
variation and inappropriate responses to the queues, rather than a capacity
shortage. A number of collaborative programs recently have come to grips with
many of the causes of the queues in both elective care and emergency care.
Although there are still areas that need large-scale improvement, good progress
has been made, especially within emergency care. The authors of this article have
acted as technical advisors to a number of these improvement programs and have
been able to document many of the practices that have helped to reduce or
eliminate unnecessary queues and delays across the 200 sites in England that have
24-hour emergency care facilities. Local program managers at these sites
continuously reported progress for a period of 18 months. A number of important
lessons for both the design and control of healthcare processes have emerged from
the collaborative work. These lessons focus on understanding and measurement of
demand, capacity planning, reduction of introduced variation, segmentation and
streaming of work, process design, capacity yield management, and measurement of
variation.
PMID- 17039691
TI - The roles of senior management in improving hospital experiences for frail older
adults.
AB - With the aging of the population, healthcare executives are paying increased
attention to fostering safe and high-quality care for older adults who become
hospitalized. The Hospital Elder Life Program (HELP) is an evidence-based program
that has been shown to be cost-effective in reducing episodes of delirium,
functional decline, and long-term nursing home placement for older hospitalized
adults. Senior administrators are known to play a role in quality improvement,
but little is known about their roles in adopting clinical improvement programs
such as HELP. Therefore, we conducted a mixed-methods study of 63 hospitals at
different stages of adopting HELP to identify key roles and motivations of senior
management to adopt HELP and the perceived impact of HELP on patient and staff
outcomes. Our findings can be used by hospital management teams as they identify
ways to influence and benefit from efforts to improve clinical quality, safety,
and the experiences of older adults treated in their hospitals.
PMID- 17039692
TI - Implementation of the EPIC electronic medical record/physician order-entry
system.
PMID- 17039693
TI - Pregnancy-related changes in the size of uterine leiomyomas.
AB - OBJECTIVE: To describe the effects of pregnancy on the growth of leiomyomas using
sonographic measurements of leiomyomas taken longitudinally during pregnancy.
STUDY DESIGN: The study population included asymptomatic gravidas with singleton
pregnancies in whom we identified uterine leiomyomas. We included all women whose
leiomyomas were measured at least twice during the pregnancy. In a subgroup of
women we also compared the size of leiomyomas before and after the index
pregnancy. Using real-time sonography, we measured each leiomyoma in 3 axes and
averaged the measurements. During subsequent studies we calculated the percent
change in the size of each tumor. We assessed complications related to the
presence of these tumors. RESULTS: We evaluated 137 leiomyomas in 72 women
(average, 2.3 +/- 1.8 per woman). Each underwent an average of 3.7 +/- 2.1 scans.
The average gestational age at the time of first assessment was 14.4 +/- 5.4
weeks. The average diameter of the leiomyomas at the first study was 34.2 +/- 23
mm. On average, there was no significant change in the size of leiomyomas during
pregnancy. We found that the size, location and our ability to visualize
leiomyomas varied significantly during pregnancy. Four of the 72 women had
obstetric complications related to the presence of leiomyomas. CONCLUSION: The
findings of our longitudinal sonographic assessment of 137 uterine leiomyomas
suggest that despite the commonly held belief that they tend to enlarge during
the course of pregnancy, this phenomenon is in fact quite rare.
PMID- 17039694
TI - First-time births among women 30 years and older in the United States: patterns
and risk of adverse outcomes.
AB - OBJECTIVE: To update the trends in initiation of childbirth by age of the mother,
describing the characteristics of women having their first child at age 30 or
above, and to determine the risk for adverse pregnancy outcomes for this group of
women. STUDY DESIGN: This was a cross-sectional study using National Center for
Health Statistics linked live birth and infant death cohort files from 1995 to
2000, and Natality file from 1980 to 2002. Analysis was limited to index
pregnancies only. Logistic regression analysis was used to determine the risk of
poor outcomes. RESULTS: There is a decreasing trend of first-time births to women
20-29 years old, while births to women 30 and older are showing a continued rise.
As compared to 20-29-year-olds, women who start childbearing at age 30 or older
are at increased risk of maternal complications in general. However, 30-34-year
olds have a reduced risk for pregnancy-induced hypertension and pre-existing
hypertension. Infants born to women aged 30 and above are at increased risk for
prematurity and low birth weight in addition to fetal and infant mortality.
CONCLUSION: Because of the increasing trend of women starting childbearing in
their 30s and the increased risk for poor outcomes in older women, health
providers need to pay extra attention to this group of women as they plan and
deliver services for them.
PMID- 17039695
TI - Effectiveness of intraoperative ultrasound in reducing recurrent fibroids during
laparoscopic myomectomy.
AB - OBJECTIVE: To detect and study residual fibroids, their recurrence after
laparoscopic myomectomy (LM) and the risk factors. STUDY DESIGN: A prospective
analysis (Canadian Task Force classification II-1) was conducted at a university
affiliated hospital. A total of 42 patients who underwent LM underwent contact
ultrasonography (CUS) and transvaginal ultrasonography (TVUS) to detect residual
fibroids. After LM, additional enucleation guided by CUS was performed, and then
the final residual fibroids were detected using TVUS. The frequency of
postoperative residual fibroids and their characteristics were evaluated. All
cases were followed for > 6 months postoperatively to assess recurrence. RESULTS:
The total number of fibroids enucleated in the initial enucleation was 201, or
4.8 per patient. Median diameter of the largest fibroids for each patient was 60
mm. There were 25 additional fibroids enucleated with CUS guidance. Their median
diameter was 12.1 mm. After the additional enucleation, 33 final residual
fibroids were identified by TVUS. Their median diameter was 9.0 mm, which was
significantly smaller than those of the additionally enucleated fibroids (p =
0.002). The frequency of patients with residual fibroids was calculated in
relation to the number of enucleated fibroids. The results showed that the
frequency tended to increase as the number of fibroids increased and that almost
all the patients (7 of 8 cases, 87.5%) with > or = 10 fibroids had residual ones.
The median follow-up period was 31 months (range, 6-37), and 8 cases (19.0%) had
recurrent fibroids. The recurrence rate in patients with > or = 10 fibroids was
50%. CONCLUSION: Intraoperative CUS was useful in detecting and enucleating
residualfibroids. As the number of enucleated fibroids increased, the risk of
residual fibroids and recurrence tended to increase.
PMID- 17039696
TI - Impact of abnormal results of outpatient fetal heart rate monitoring on maternal
intervention in labor.
AB - OBJECTIVE: To conduct a retrospective, cohort study to determine the impact of
abnormal outpatient fetal heart rate (FHR) testing on maternal interventions in
labor, including labor induction, operative vaginal delivery and unplanned
cesarean section. STUDY DESIGN: Our cohort consisted of 1,386 women with
singleton gestations who had outpatient fetal nonstress testing within 1 week
prior to giving birth etween 1993 and 1998. Antepartum FHR records were
interpreted as reassuring or nonreassuring, and pregnancy records were abstracted
for background medical information, labor interventions and pregnancy outcomes.
Logistic regression models were used to describe the association between abnormal
outpatient monitoring results and maternal interventions in labor. RESULTS: After
adjusting for potential confounders (maternal age, race, prior history of
cesarean section, antepartum indications for monitoring, fetal presentation and
abnormal fetal heart rate patterns in labor), women with nonreassuring monitoring
were 90% more likely to undergo induction. The 2 groups were similar in operative
vaginal delivery rates, but pregnancies with nonreassuring testing were more than
twice as likely to end with an unplanned cesarean section. CONCLUSION: Abnormal
outpatient antenatal FHR testing may be independently associated with an
increased risk of unplanned cesarean section.
PMID- 17039697
TI - Mechanisms of twinning: VIII. Maternal height, insulinlike growth factor and
twinning rate.
AB - OBJECTIVE: To evaluate the relationship of maternal height to the rate of
twinning and the possible connection of these parameters to the coexistent level
of insulinlike growth factor (IGF). STUDY DESIGN: Since spontaneous multiple
gestations in humans are relatively uncommon in general, it is reasonable to
consider distin guishing physical attributes such as height, that may have some
functional relationship to this phenomenon. In a prior study, hereditary and
dietary factors affecting the level of IGF were found to correlate with the rate
of twinning. In that height is known to parallel the serum level of IGF, a survey
of women who had previously conceived spontaneously and had given birth to twins
or triplets was undertaken. Their heights were compared with the mean value for
the general female population, RESULTS: Mothers of 129 sets of spontaneous
multiples displayed a mean height of 164.8 cm as compared to 161.8 cm for the
general population of women (p < 0.005). CONCLUSION: These data confirm those
from previous studies and corroborate the proposed relationship between maternal
height and the rate of twinning. Thus, the results reported here further support
the IGF model of twinning.
PMID- 17039698
TI - Prenatally diagnosed balanced chromosome rearrangements: eight years' experience.
AB - OBJECTIVE: To investigate the incidence and pregnancy outcome of prenatally
diagnosed balanced chromosome rearrangements from amniocentesis. STUDY DESIGN:
Between January 1996 and December 2003, we collected cases with balanced
chromosome rearrangements from amniocentesis specimens submitted to our
cytogenetics laboratory for fetal karyotyping. Data on maternal age, indication
for amniocentesis, detailed anatomic sonographic findings, gestational age at
delivery, newborn birth weight and infant anomalies, if any, were obtained by
chart review. RESULTS: A total of 66 cases of balanced chromosomal translocations
or inversions were identified from the 12,468 amniocentesis specimens.
Specifically, 0.256% had a reciprocal translocation, 0.080% had a Robertsonian
translocation, and 0.192% had an inversion. The incidences of de novo reciprocal
translocations, Robertsonian translocations and inversions were 0.080%, 0.016%
and 0.024%, respectively. Abnormal prenatal sonographic findings occurred in 2
cases, 1 in an inherited case and 1 in a de novo case. Abnormal postnatal
findings occurred in 5 cases, 3 in inherited cases and 2 in de novo cases.
Excluding the cases with minor congenital anomalies, the major congenital anomaly
rates of inherited and de novo chromosome rearrangements were 1.96% and 6.66%,
respectively. CONCLUSION: The incidences of prenatally diagnosed de novo
reciprocal translocations, de novo Robertsonian translocations and de novo
inversions were higher than those reported in previous, larger series. The major
congenital anomaly rates for inherited and de novo chromosome rearrangements were
higher than the 1.4% congenital anomaly rate in our general population.
Consequently, detailed ultrasound examination and parental karyotyping should be
viewed as essential measures in dealing with prenatally diagnosed balanced
chromosome rearrangements.
PMID- 17039699
TI - Relationship between meconium staining, umbilical cord plasma motilin level and
infantile colic.
AB - OBJECTIVE: To assess the effects of meconium-stained amniotic fluid and umbilical
cord plasma motilin levels on the development of infantile colic. STUDY DESIGN:
One hundred forty pregnant women referred to our department for labor care were
enrolled in the study. All subjects were laboring women with singleton, vertex
presenting fetuses, with a gestational age of > or = 36 weeks. After each infant
with meconium-stained amniotic fluid was born, the following 2 infants without
meconium were selected as controls. Umbilical cord plasma motilin levels were
measured in 47 infants with meconium-stained amniotic fluid and 93 infants with
no meconium. At the end of the third month of the infants' lives, the development
of infantile colic was evaluated. Umbilical cord serum specimens were collected
from 45 infants with colic and 95 infants without colic. Statistics included
Student's t, chi2 and Mann-Whitney U tests, as appropriate. Multivariate analysis
was performed. RESULTS: There was no correlation between the presence of meconium
stained amniotic fluid and the development of infantile colic. No association was
found between umbilical cord plasma motilin levels and the development of
infantile colic. Neonatal intensive care unit admission was found to be a
significant risk factor for the development of infantile colic. CONCLUSION:
Meconium-stained amniotic fluid and umbilical cord plasma motilin levels do not
affect the development of infantile colic.
PMID- 17039700
TI - Alternate evaluations of proteinuria in the gravid hypertensive patient.
AB - OBJECTIVE: To determine if the 12-hour urine total protein value correlates with
the 24-hour value and to evaluate the random protein:creatinine ratio as a
predictor of significant proteinuria (> or = 300 mg/24 h) for use in diagnosing
preeclampsia. STUDY DESIGN: The study population included 15 patients with
hypertensive disorders of pregnancy. The patients' urine was collected over 24
hours in 2 12-hour aliquots. The urine volume, total protein and creatinine were
measured. The patients' initial voids were collected and evaluated for random
urine protein and creatinine and calculation of the protein:creatinine ratio. The
protein:creatinine ratio and 12-hour results were compared to the 24-hour results
using simple regression analysis. RESULTS: Of the 15 patients, 6 had no
proteinuria, 5 had mild proteinuria, and 4 had severe proteinuria (60% with
significant proteinuria). The 12-hour protein results correlated with the 24-hour
results for patients with mild disease (p = 0.00007, first 12 hours, and p =
0.012, second 12 hours) and severe disease (p = 0.014 and p = 0.007). The results
for no disease were mixed: for the first 12 hours there was a poor correlation,
but the results for the second 12 hours correlated well. The protein:creatinine
ratio had a significant correlation (p = 0.02), using a cutoff of 0.15, returned
specificity of 50%, sensitivity of 100%, positive predictive value of 75% and
negative predictive value of 100%. CONCLUSION: Total protein values for 12- and
24-hour urine samples correlate well for the diagnosis of preeclampsia. A
protein:creatinine ratio of < or = 0.15 rules out significant proteinuria. In
combination, these 2 tests may allow more rapid diagnosis of preeclampsia.
PMID- 17039702
TI - Pregnancy in a woman with a continent appendicovesicostomy: a case report.
AB - BACKGROUND: Few cases of pregnancy following the Mitrofanoff procedure (continent
appendicovesicostomy) have been reported, but in those cases there was an
increased rate of cesarean delivery with no long-term consequences to renal
function or to the urinary diversion. CASE: A 15-year-old primagravida with a
prior nephrectomy for a dysplastic kidney and prior continent
appendicovesicostomy for urinary retention due to spina bifida occulta and
neurogenic bladder had a pregnancy complicated by preterm premature rupture of
membranes, preterm labor, breech presentation and cesarean delivery with the
assistance of a urologist. The patient had a minimal decline in renal function,
and she and the infant did well. CONCLUSION: Cesarean delivery should be reserved
for obstetric indications. Surgical assistance by a urologist at the time of
cesarean delivery may be helpful.
PMID- 17039701
TI - Pulmonary benign metastasizing leiomyoma: a report of 2 cases with different
outcomes.
AB - BACKGROUND: Benign metastasizing leiomyoma (BML) of the lung is a rare
manifestation of metastasis from a uterine myoma, in which its benign
characteristics are maintained. The majority of cases are asymptomatic. CASES:
Case 1 responded to the classic treatment of oophorectomy, after which an
improvement in symptoms was achieved. In case 2, however, symptoms appeared
following oophorectomy and were treated with raloxifene. CONCLUSION: These cases
show the uncertainty that exists with respect to the evolution and treatment of
symptomatic BML. Raloxifene is a therapeutic agent that has not been widely
studied for this purpose but should be considered for inclusion in the arsenal of
therapeutic options available.
PMID- 17039703
TI - Spontaneous rupture of uterine surface varicose veins in pregnancy: a case
report.
AB - BACKGROUND: Spontaneous rupture of uterine surface varicose veins is rare but may
become a serious complication of pregnancy. CASE: A 40-year-old woman, gravida 2,
para 0-0-1-0, presented with worsening generalized abdominal pain after
occasional nausea, vomiting and diarrhea over the previous 2 days. After a 4-hour
observation period, sudden onset of severe, prolonged fetal heart rate
decelerations was recognized along with frequent uterine contractions. Emergency
cesarean section was performed under a tentative diagnosis of placental
abruption. A live, female infant weighing 1,730 g was delivered and had Apgar
scores of 5 and 9 at 1 and 5 minutes, respectively. Intraoperatively,
approximately 500 mL of hemoperitoneum was present, and multiple bleeding sites
from varicose veins on the posterior uterine surface were detected. Because the
maternal vital signs became unstable and hemostasis was difficult, hysterectomy
was performed and blood transfusion administered. CONCLUSION: Although very rare,
hemoperitoneum should be included in the differential diagnosis when a pregnant
woman experiences acute-onset, severe abdominal pain, even without an episode of
abdominal trauma.
PMID- 17039704
TI - Arrhythmogenic right ventricular dysplasia in pregnancy: a case report.
AB - BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by
progressive fibrous or fibrofatty tissue replacement of the right ventricular
myocardium. Interspersed adipocytes and fibrous tissue may provide foci for
arrhythmias. The clinical spectrum of ARVD may include asymptomatic premature
ventricular complexes to ventricular tachycardia and sudden death. There is
currently little information about ARVD in pregnancy. CASE: A 29-year-old
primigravida, diagnosed with ARVD 1 year prior to pregnancy, underwent a full
term, uncomplicated pregnancy and delivery while maintained on acebutolol and an
implanted cardioverter defibrillator. Her infant was born without an apparent
cardiac anomaly or heart rate abnormality. CONCLUSION: Successful management of
pregnancy complicated by ARVD can be accomplished with an implanted cardioverter
defibrillator and an antiarrhythmic agent. Such patients should be managed with
close monitoring during pregnancy for signs and symptoms of arrhythmia and
preventive obstetric care appropriate to their clinical profile to optimize
normal deliveries.
PMID- 17039705
TI - Heterotopic pregnancy after 2 prior ectopic pregnancies: a case report.
AB - BACKGROUND: Heterotopic pregnancy is a rare occurrence, with spontaneous
pregnancy often unsuspected and associated with delayed diagnosis. When previous
ectopic pregnancy has been treated, future pregnancy is associated with an
increased risk for ectopic pregnancy and potentially heterotopic pregnancy.
Conservative treatment for ectopic pregnancy with either surgery or methotrexate
leaves the patient with hope for potential future fertility, especially when
assisted reproductive technology is not available. CASE: A woman who had been
treated for ectopic pregnancy in both fallopian tubes presented with a
spontaneous heterotopic pregnancy. CONCLUSION: Heterotopic pregnany may occur
after treatment of previous ectopic pregnancy and may lead to a successful
outcome when diagnosed and treated appropriately.
PMID- 17039706
TI - Incisional bladder hernia and refractory urinary urgency after pelvic surgery: a
case report.
AB - BACKGROUND: Isolated incisional herniation of the bladder is very rare following
pelvic surgery and may present as suprapubic discomfort. We report a case of
incisional bladder hernia following pelvic surgery presenting as refractory
urinary urgency. CASE: A 70-year-old woman, para 2, presented with a long history
of suprapubic tenderness and refractory urinary urgency following reconstructive
pelvic surgery. Over the 3 years following her surgery, multiple physicians
evaluated the patient but were unable to find a definitive source of her urgency.
She had used multiple anticholinergic agents without relief of the symptoms. A
complete urogynecologic evaluation, radiologic imaging and high clinical
suspicion for incisional hernia revealed a bladder hernia. Surgical exploration
confirmed the fascial defect and bladder hernia. Herniorrhaphy corrected the
defect and relieved the patient's symptoms of refractory urgency. CONCLUSION: An
incisional bladder hernia may present as refractory urinary urgency following
reconstructive pelvic surgery. Strong clinical suspicion can allow earlier
diagnosis and surgical treatment of this rare condition. Primary herniorrhaphy
offers successful repair of the fascial defect and resolution of the urgency
symptoms.
PMID- 17039707
TI - Latent pelvic tuberculosis reactivating in a postmenopausal woman: a case report.
AB - BACKGROUND: Tuberculosis most often affects the pulmonary system; however, 8-15%
of cases infect the genitourinary system. The primary treatment of uterine
tuberculosis is medical therapy, and only when that fails is surgical
intervention warranted. CASE: A 75-year-old woman presented with chronic back
pain and fatigue. She had been on prednisone for 9 years for autoimmune hepatitis
and had earlier exposure to tuberculosis. Evaluation led to the diagnosis of
uterine tuberculosis. The patient was unable to tolerate a full course of
antituberculin therapy, so she underwent an abdominal hysterectomy and bilateral
salpingo-oophorectomy. CONCLUSION: We believe the patient had latent uterine
tuberculosis that was reactivated from her chronic steroid use. If she had a
purified protein derivative test prior to the start of prednisone therapy, latent
tuberculosis may have been diagnosed and treated before she developed a
clinically active infection.
PMID- 17039708
TI - Small bowel volvulus after uterine artery embolization requiring bowel resection:
a case report.
AB - BACKGROUND: Previously described surgical complications following uterine artery
embolization for leiomyomata include sequelae of uterine aberrant embolization
(buttock and labial necrosis, vesicouterine fistula), prolapsed cervical myoma,
uterine necrosis, ischemic uterine rupture and sepsis. CASE: A 43-year-old woman
presented with severe abdominal pain, nausea and vomiting 7 days after bilateral
uterine artery embolization for symptomatic leiomyomata. Mechanical obstruction
of the distal ileum was diagnosed and did not respond to conservative measures.
At laparotomy, volvulus of the distal ileum, which adhered to omental and uterine
adhesions, required resection and end-to-end anastomosis. CONCLUSION: Volvulus
may occur following uterine artery embolization for leiomyomata.
PMID- 17039709
TI - Symptomatic cesarean scar diverticulum: a case report.
AB - BACKGROUND: Extrauterine lesions of intermediate trophoblast have occurred in and
around fallopian tubes and ovaries and are thought to result from an exaggerated
trophoblastic response to the implantation site of a previous ectopic pregnancy.
Additionally, cesarean scar defects have recently been identified as a source of
persistent, irregular vaginal bleeding in women and can be identified by pelvic
ultrasound. CASE: A 35-year-old woman presented with irregular vaginal bleeding
in association with an anterior extrauterine cystic mass detected by pelvic
ultrasound and thought to represent a cesarean scar defect. Subsequent histology
revealed an endometrial diverticulum lined with chorionic-type intermediate
trophoblast, a subpopulation of trophoblast that composes placental site nodules.
CONCLUSION: This was the first case of a lesion of intermediate trophoblast
occurring in a cesarean scar diverticulum.
PMID- 17039711
TI - Huge leiomyoma in a woman with Down syndrome: a case report.
AB - BACKGROUND: For patients with Down syndrome, the reproductive period is becoming
longer in relation to the increasing lifetime. Thus, the possibility of
reproductive disorders is also increasing. CASE: A 37-year-old woman with trisomy
21 was hospitalized with uterine myomatosis, which was spreading to the
umbilicus. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were
performed, and estrogen replacement was given after surgery. CONCLUSION: The
incidence of solid tumors in Down syndrome patients is extremely rare or
nonexistent. This case calls attention to reproductive pathology in long-lived
women with Down syndrome.
PMID- 17039710
TI - Keratinizing squamous cell carcinoma of the cervix in a sexually inexperienced
woman: a case report.
AB - BACKGROUND: Even though cervical cancer is largely considered to be a sexually
transmitted disease with a viral etiology, other modes of transmission are
theoretically possible. CASE: A 38-year-old woman with cervical squamous cell
carcinoma adamantly denied having ever had sexual intercourse due to personal,
religious and cultural beliefs. CONCLUSION: Because the human papillomavirus may
be spread via nonsexual means, Pap smear screening in sexually active and
inexperienced women is important.
PMID- 17039712
TI - Term delivery of the second twin after miscarriage of the first: a case report.
AB - BACKGROUND: Term delivery of the second twin after miscarriage of the first twin
is rare. There is always a risk of preterm delivery as well as infection leading
to chorioamnionitis. CASE: The second twin was delivered at term after
miscarriage of the first twin at 17 weeks'gestation. The pregnancy was carefully
monitored for prevention and early detection of chorioamnionitis. Delivery was
delayed to 30 weeks after the miscarriage of the first twin, with a good outcome.
CONCLUSION: Delayed delivery of the second twin with conservative management
clearly is of benefit.
PMID- 17039714
TI - McKinsey 'PCT support' bid sparks conflict-of-interest row.
PMID- 17039713
TI - Pelvic pain associated with an unsuspected intraomental intrauterine device
placed 30 years earlier: a case report.
AB - BACKGROUND: Recent-onset chronic pelvic pain thought to originate from an
intraomental Dalkon Shield intrauterine device (IUD) (A. H. Robbins, Inc.,
Richmond, Virginia) that had remained asymptomatic for over 30 years is unusual.
Case reports and patient series suggest that intraomental IUDs remain
asymptomatic for long periods of time and are usually not associated with chronic
pelvic pain. CASE: A 49-year-old woman with an unrecollected history of Dalkon
Shield placement 30 years earlier was evaluated after 6 months of pelvic pain. A
negative workup and failure of conservative management prompted an abdominal
hysterectomy with bilateral salpingooophorectomy, which failed to relieve the
symptoms. Revaluation identified a mobile, intraabdominal Dalkon Shield. Real
time x-ray fluoroscopy and reverse Trendelenburg positioning were used to
laparoscopically retrieve the IUD from the patient's benign-appearing omentum.
The pelvic pain remained resolved for over 1 year after removal of the IUD.
CONCLUSION: An intraomental IUD that remained asymptomatic for 30 years was the
most likely source of chronic pelvic pain in this perimenopausal patient.
Increased intraabdominal fat deposition associated with the perimenopause may
have contributed to this patient's change in clinical status.
PMID- 17039715
TI - Four in five spearhead PCTs fall behind on inequalities.
PMID- 17039716
TI - Charities fear 'nuisance' penalties.
PMID- 17039717
TI - Are paid-up ITC millions being consigned the scrapheap?
PMID- 17039718
TI - On iSoft--the inside story.
PMID- 17039719
TI - Barometer. Public health September 2006.
PMID- 17039720
TI - Fraud. Your cheating art.
PMID- 17039721
TI - Staff management. Soft solutions.
AB - The projected spend on NHS agency staff for 2005-06 is around pounds sterling
1bn. Some trusts spend significantly more than 10 per cent of their total pay
bill on non-NHS staff. NHS Employers points to huge potential savings from e
rostering. The software dramatically cuts time spent preparing rotas and also
produces useful management information.
PMID- 17039722
TI - Cutting edge care.
PMID- 17039723
TI - Assistive technology. Home comforts.
PMID- 17039724
TI - Health hotel: Finance. Golden wonder.
PMID- 17039725
TI - Health hotel: welfare and health. What about the workers?
PMID- 17039726
TI - Health hotel: access and choice. Lofty ambitions.
PMID- 17039727
TI - Health hotel: quality of service. Safe as houses.
PMID- 17039728
TI - [Virological diagnosis and follow-up of HIV infection. State of the art and
situation in Tunisia].
AB - Human immunodeficiency virus (HIV) is a retrovirus infecting approximatively 40
million people worldwide. HIV is characterized by a great variability with
epidemiological, diagnostic and therapeutic implications. The course of infection
goes through three stages (acute infection, clinical latency and AIDS) with the
evolution of virological markers (anti-HIV antibodies, p24 antigenemia, plasma
RNA and proviral DNA). Direct virological diagnosis is mainly based on molecular
tools allowing viral genome detection and amplification with specific primers and
nucleic probes besides p24 antigenemia detection, and more rarely viral culture.
Antigenic properties of viral proteins elicit in infected patients antibody
synthesis, which is detected using serology (ELISA and Western blot tests). The
follow-up of infected patients is carried out with plasma HIV-1 RNA quantitation
and phenotypic or genotypic characterization of variant isolates. Virological
tests are prescribed according to clinical presentation (screening, acute
infection, newborn from HIV-infected mother). Most of these virological tools are
available in Tunisia, allowing both diagnosis of HIV infection and monitoring of
infected individuals. Regarding diagnostic tests indication and interpretation,
multidisciplinary concertation is hopeful in order to optimize patient
management.
PMID- 17039729
TI - [Microscopic colitis. A 20 cases series].
AB - Microscopic colitis are defined as a chronic inflammation of a normal macroscopic
colonic mucosa. We report 20 cases of microscopic colitis. Chronic diarrhea
revealed the diagnosis in 95% of cases. Endoscopic examination was normal in 95%
of patients. We diagnosed collagenous colitis in 65% of cases and lymphocytic
colitis in 35% of cases. The treatment was based on sulphasalazine in 16
patients, on 5 aminosalicylic acid in 1 case, on gluten free diet in 2 cases and
a symptomatic treatment was prescribed to one patient. A clinical remission was
observed in 41.2% of patients taking sulphasalazine.
PMID- 17039730
TI - [Superficial fungal infections. Epidemiologic, clinical and mycologic study over
a three year period].
AB - The object of our study is to release the epidemiological, clinical and
mycological characteristics of superficial fugal infections. A retrospective
study was carried out during three years (1996-1998). Direct microscopy was
positive in 86% cases, the culture in 62% cases. Trichophyton rubrum accounts for
85% of the dermatophytic flora. The superficial fugal infections account for 15%
of the reasons for consultation in our service. They would touch according to
data's of literature 2 to 13% of the general population. Trichophyton rubrum in
accordance with the various series published, is the fungi most frequently
insulated with variable rates between 46 and 82% of the superficial fungal
infections. Any time, Candida albicans is prevalent on the level of the hands.
PMID- 17039732
TI - [Epidemiologic and clinical features of patients with type 2 diabetes mellitus in
primary care facilities (Sousse, Tunisie)].
AB - As a result of epidemiologic transition, diabetes mellitus became a major public
health problem in Tunisia. We tried to determine the epidemiological and clinical
features of patients with type 2 diabetes mellitus in primary health care units
in Sousse (Tunisia). It was a cross sectional study about a stratified sample of
404 type 2 diabetes mellitus patients followed in primary care offices in Sousse
in 2003. Average age was 60 + 10.9 years and sex-ratio was 0.5. Hypertension and
obesity were found in respectively 71.3% and 37.6%. Diabetic neuropathy was the
most frequent degenerative complication (41.1%) followed by diabetic retinopathy
(18.3%). Thus, type 2 diabetes mellitus patients, followed in primary care units
show a high cardiovascular risk with serious and frequent complications. That's
why, the national care program of type diabetes mellitus, in primary health care
should take in consideration, in its guidelines, the clinical and epidemiological
characteristics of these patients.
PMID- 17039731
TI - [Premature ovarian insufficiency. Analysis of 30 cases].
AB - Premature menopause is a relatively rare disease but it has delicate consequences
dominated by infertility problems. Most often, etiologic investigation is
disappointing. Helped in some cases by the association to some auto-immune
diseases or a previous treatment with chemotherapy or an irradiation may be
useful to understand the origin of the premature ovarian failure. We analyse in
this paper 30 cases of premature menopause to try to precise its etiologic
factors, its diagnosis tools, the fertility prognostic and the therapeutic
possibilities
PMID- 17039733
TI - [Mal de Meleda. 16 cases].
AB - Mal de Meleda is a recessive transgression palmoplantar keratoderma. We report
the epidemiological, clinical and progressiveness aspects of the disease in 16
patients of a large consanguineous tunisian family. The age ranged from 3 to 90
years. Nine were male and 7 female patients. Onset in early infancy was
characterized by erythema of the palms and soles, followed by a diffuse yellowish
hyperkeratosis. Thickness of the dorsal aspect of the fingers started in
childhood. Extension of hyperkeratosis to the dorsal of the hand were reported
only in adults and usually precede the involvement of the feet Palmoplantar
hyperhidrosis with fetid odor between the toes was frequently seen as well as
conical distal phalanges. In some adults keratoderma gave contracture of the
fingers leading to limitation of movements Mal de Meleda must be differentiated
from other recessive palmoplantar keratoderma such as Papillon-Lefevre syndrome
and Mal de Naxos. the remaining inherited palmoplantar keratoderma being
autosomal dominant. Mal de Meleda is a rare disease but is still relatively
frequent in some tunisian regions, due to the high rate of consanguinity Mal de
Meleda remains an afflicting and disabling disease.
PMID- 17039734
TI - Co-analgesic effect of ketorolac after thoracic surgery.
AB - Thoracotomies are painful surgical procedures and adequate pain relief is
associated with improved respiratory function and fewer respiratory
complications. After thoracotomy for lung resection, patients received morphine
based patient-controlled analgesia (PCA). Three groups were prospectively and
randomised investigated: patients receiving preemptive ketorolac, those given
postoperative ketorolac and controls. No differences among groups were found for
demographic data, anaesthesia and surgery durations, or for the amounts of
anaesthesia drugs administered. The blood losses were also comparable: 565 +/-
374 ml for the preemptive ketorolac group. 749 +/- 491 ml for the postoperative
ketorolac group and 674 +/- 323 ml for the controls. At 48 h after surgery,
compared to controls, morphine consumption was 36% lower for the preemptive
ketorolac group and 17% lower for postoperative ketorolac group (p < 0.05). No
statistically significant differences were observed for pulmonary function tests.
These results suggest that non-steroidal anti-inflammatory drugs can reduce the
opioid requirements after thoracic surgery but do not improve lung function.
PMID- 17039735
TI - [Clinical features and treatment in Cushing's disease. 18 cases].
AB - We report a retrospective study about 18 Cushing's diseases in the department of
endocrinology at Charles Nicolle hospital in 24 years. The mean age was 33.7
years with a male-female ratio of 4/14. Diagnosis was established on
adrenocorticotropin hormone analysis and pituitary imaging. Transsphenoidal
adenomectomy was released in 8 cases of Cushing's disease, it was successful in 5
patients (62.5%). Bilateral adrenalectomy was performed in three cases.
PMID- 17039736
TI - [Radon in Tunisian buildings].
AB - Radon is a natural radioactive gas produced by decay of uranium and radium
present in soils. Diluted in air, in confined atmospheres, it may accumulate in
high concentrations. Inhalation of radon and its progeny is thought to increase
lung cancer risk. For the first time, air radon concentrations were determined in
1151 dwellings situated in all the inhabited regions of Tunisia, using open alpha
track dosimeters exposed during two months. The median of 1864 measurements was
36 Bq m(-3) (with a maximum of 512 Bq m(-3), most of them being less than 100 Bq
m(-3). All results were under the International Instances recommended range.
PMID- 17039737
TI - [Adult-onset Still disease. 11 cases].
AB - Still's Disease of the adult is a systemic disease that the cause is unknown. If
the pediatric forms are frequent, the affection of the adult is rare and its
diagnosis is difficult. The purpose of this study is to analyse the features of
the clinical evolution of adult Still's disease and to compare our results with
the literature. It is a retrospective study about 21 years that permitted to
collect 11 cases according the criteria of Yamaguchi. It is a matter of 6 men and
5 women that the mean age is 31 years old (age range: 16 to 48 years old). The
fever was constant, the skin rash was noticed in 8 patients (72.7%); a
polyarthritis was noticed in all the patients, chronic in 10 cases (90.9%) which
2 erosive forms. Adenopathies were present in 5 patients, a splenomegaly and a
hepatomegaly were noticed respectively in 4 and 2 cases. Inflammatory syndrome
with hyperleukocytosis was constant, and a hepatic cytolysis was noticed in 80%.
The total ferritinemia titrated in 8 patients was constantly high. The
hemocultures realized in all the patients were sterile and the complete
immunologic examination was negative. The strong dose of corticoid was prescribed
with success in all the patients. The immediate evolution was favourable in 10
patients. We deplore one death after a state of deep denutrition. Still's disease
of the adult is rare, its diagnosis is difficult, sensitive to corticotherapy and
its clinical evolution in our country is comparable to the literature.
PMID- 17039738
TI - [Giant placental chorioangioma].
AB - The large placental chorioangioma is a non-trophoblastic vascular tumor of
placenta which size is more than 4 cm. It's a rare tumor, the incidence is
between 1/3500 and 1/9000 birth. We analyze, on base of our case and from a
literature review, the ultrasonography aspects of this tumor: we bring out also
the physiological mechanisms of maternal and fetal complications and finally we
detail the therapeutic possibilities. Chorioangioma appears in ultrasound scan
like a thoroughly limited hypo-echogenic zone The vascular origin of the tumor
can be confirmed by color Doppler. A left-right shunt effect results from arterio
venous communications and causes backwardness growth and fetal death in-utero The
fetus is exposed to anemia and microangiopathic thrombopenia The maternal
complications are: hydramnios, abruption placenta, premature ruptured membrane.
Therapeutic possibilities are reduced: In several fetal anemia, blood transfusion
can be done. Some techniques for tumor devascularization are be tried by someone.
PMID- 17039739
TI - [Inflammatory fibroid polyp of the ileum presenting as intussusception: a case
report in an adolescent].
AB - Inflammatory fibroid polyp is an uncommon and benign submucosal lesion of the
gastrointestinal tract. The maximal incidence is in the fifth and sixth decades.
The main histological characteristics are diffuse inflammatory infiltrate with
eosinophils and highly vascularized fibrocystic stroma. We report a case of 15
year-old patient who underwent emergency surgery because of acute intestinal
obstruction as a result of an intussusception. The macroscopical study after
segmental ileal resection showed a nodular lesion 3x2x2 cm, arising from the
submucosa with an ulcerated surface. The pathologic diagnosis was ileal
inflammatory fibroid polyp. Immunohistochemically, the cells reacted with
vimentin and CD34. It has no malignant potential although extensive infiltration
may occur. The etiology is unknown. We discuss the clinical, the pathological
aspects and the possible etiological factors of the inflammatory fibroid polyp.
PMID- 17039740
TI - [Prune belly syndrome: early prenatal diagnosis and management].
AB - Prune Belly syndrome is characterized by a combination of megacystis, anterior
abdominal wall distension with deficiency of the abdominal wall musculature, and
bilateral cryptorchidism. Diagnosis is easy after 15 weeks of gestation, but may
be difficult at the end of the first term. Authors report 2 cases of Prune Belly
syndrome diagnosed at 11 and 14 weeks of gestation respectively. After literature
review, diagnosis and prognosis particularities of this syndrome are discussed.
PMID- 17039741
TI - [Pelvic ganglioneuroma. Report of a case].
AB - Ganglioneuroma is a rare benign tumor. It is the most mature of neurogenic
tumors. We report a case of a pelvic ganglioneuroma diagnosed in 24-year-old
pregnant woman who presented with an urinary infection. Echographic examination
suggested an ovarian mass. At surgical operation, the tumor was close to the
sacrum. A total resection of the tumor was performed. Pathological examination
proved it as a ganglioneuroma. Sixteen months later, the patient is free from
disease.
PMID- 17039742
TI - [Deficient expression of leukocyte adhesion proteins. A new Tunisian case].
AB - Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency inherited
as an autosomal recessive genetic disorder. LAD was suspected in a four days old
girl. She was born from healthy first cousins. A family history of a boy who died
from omphalitis and sepsis was reported. Our patient had the severe form, she had
delayed umbilical cord separation and suffered recurrent infections. She had a
deletion of the G at position 1497. The patient received bone marrow
transplantation from her HLA-identical mother at age of 14 months. She is now 9
years old and in good health.
PMID- 17039743
TI - Clarification of guidelines for the proper use of child car seats.
PMID- 17039744
TI - Health care for the homeless in America.
PMID- 17039745
TI - Imperative integration: medical care for older patients.
PMID- 17039746
TI - Vaccines for preventing influenza in healthy children.
PMID- 17039747
TI - Expectant management vs. surgical treatment for miscarriage.
PMID- 17039748
TI - Exercises for mechanical neck disorders.
PMID- 17039749
TI - The homeless in America: adapting your practice.
AB - In 2004, the National Guidelines Clearinghouse placed eight guidelines from the
National Health Care for the Homeless Council on its Web site. Seven of the
guidelines are on specific disease processes and one is on general care. In
addition to straightforward clinical decision making, the guidelines contain
medical information specific to patients who are homeless. These guidelines have
been endorsed by dozens of physicians who spend a large part of their clinical
time caring for some of the millions of adults and children who find themselves
homeless each year in the United States. In one guideline, physicians are
prompted to keep in mind that someone living on the street does not always have
access to water for taking medication. Another guideline points out the
difficulty of eating a special diet when the patient depends on what the local
shelter serves. As the number of homeless families and individuals increases,
family physicians need to become aware of medically related information specific
to this population. This can help ensure that physicians continue to offer
patient-centered care with minimal adherence barriers.
PMID- 17039750
TI - Kawasaki disease: summary of the American Heart Association guidelines.
AB - Kawasaki disease is an acute vasculitis of childhood that predominantly affects
the coronary arteries. The etiology of Kawasaki disease remains unknown, although
an infectious agent is strongly suspected based on clinical and epidemiologic
features. A genetic predisposition is also likely, based on varying incidences
among ethnic groups, with higher rates in Asians. Symptoms include fever,
conjunctival injection, erythema of the lips and oral mucosa, rash, and cervical
lymphadenopathy. Some children with Kawasaki disease develop coronary artery
aneurysms or ectasia, ischemic heart disease, and sudden death. Kawasaki disease
is the leading cause of acquired heart disease among children in developed
countries. This article provides a summary of the diagnostic and treatment
guidelines published by the American Heart Association.
PMID- 17039751
TI - Information from your family doctor. Kawasaki disease: what you should know.
PMID- 17039752
TI - Preventive health counseling for adolescents.
AB - The leading causes of adolescent mortality are accidents (death from
unintentional injury), homicide, and suicide. Additional morbidity is related to
drug, tobacco, and alcohol use; risky sexual behaviors; poor nutrition; and
inadequate physical activity. One third of adolescents engage in at least one of
these high-risk behaviors. Physicians should specifically target these risk
factors with preventive counseling, although adolescents may be reluctant to
initiate discussions about risky behaviors because of confidentiality concerns.
The key to providing relevant and useful preventive counseling for adolescent
patients is developing the trust necessary to discuss the specific issues that
impact this age group.
PMID- 17039753
TI - A practical guide to crisis management.
AB - Family physicians often treat patients who are experiencing psychological or
medical crises. Any event perceived as overwhelming by the patient may trigger a
crisis reaction consisting of psychological and physiological symptoms.
Physicians are encouraged to assist patients who are experiencing a crisis by:
(1) providing reassurance and support; (2) evaluating the nature of the problem
and determining the patient's mental, psychiatric, suicidal or homicidal, and
medical statuses; (3) ensuring the safety of the patient and others; (4)
assisting the patient in developing an action plan that minimizes distress, and
obtaining patient commitment to the plan; and (5) following up with the patient
and other relevant persons to ensure follow-through, assess progress, and provide
additional assistance and support. Medication or referral for psychiatric or
psychological counseling may be necessary for patients with continuing problems.
PMID- 17039754
TI - Information from your family doctor. Crisis management.
PMID- 17039755
TI - Growing plantar lesion following trauma.
PMID- 17039756
TI - Information from your family doctor. Colds and the flu: tips for feeling better.
PMID- 17039757
TI - Information from your family doctor. Sore throat.
PMID- 17039758
TI - Information from your family doctor. Antibiotics: when they can and can't help.
PMID- 17039759
TI - Facilitating shared decision making with patients.
PMID- 17039760
TI - In search of a best practice model for the hospital-foundation relationship.
PMID- 17039761
TI - Gaining a competitive edge: e-philanthropy and hospital development.
AB - E-philanthropy offers tremendous potential for hospital development. Using the
Internet, a hospital can efficiently communicate with current and prospective
donors, reach donors that it otherwise would not reach, and build stronger
relationships with the next generation of major and planned givers. Developing a
strategic online program will help hospitals and their associated foundations
achieve greater success and more effectively fulfill their missions well into the
future.
PMID- 17039762
TI - Tapping the river of grateful patients: principles and techniques for best
practices in patient prospecting.
PMID- 17039763
TI - Build it and they will come.
PMID- 17039764
TI - Acceptable noise level: A clinical measure for predicting hearing aid outcome.
PMID- 17039765
TI - Acceptable noise level as a predictor of hearing aid use.
AB - Acceptable noise level (ANL) measures a listener's reaction to background noise
while listening to speech. Relations among hearing aid use and ANL, speech in
noise (SPIN) scores, and listener characteristics (age, gender, pure-tone
average) were investigated in 191 listeners with hearing impairment. Listeners
were assigned to one of three groups based on patterns of hearing aid use: full
time use (whenever hearing aids are needed), part-time use (occasional use), or
nonuse. Results showed that SPIN scores and listener characteristics were not
related to ANL or hearing aid use. However, ANLs were related to hearing aid use.
Specifically, full-time hearing aid users accepted more background noise than
part-time users or nonusers, yet part-time users and nonusers could not be
differentiated. Thus, a prediction of hearing aid use was examined by comparing
part-time users and nonusers (unsuccessful hearing aid users) with full-time
users (successful hearing aid users). Regression analysis determined that unaided
ANLs could predict a listener's success of hearing aids with 85% accuracy.
PMID- 17039766
TI - Acceptable noise level: reliability measures and comparison to preference for
background sounds.
AB - The present study (1) assessed the reliability of the acceptable noise level
(ANL) measure using speech-spectrum and speech-babble noises as the competing
stimuli, and (2) investigated the relationship between ANL and preference for
background sounds in 30 young adults with normal hearing sensitivity. Listeners
were evaluated during three test sessions approximately one week apart. Results
demonstrated that ANLs are highly reliable over short periods of time,
independent of the background noise distraction. Mean ANLs, however, were
affected by type of background noise distraction, indicating ANLs obtained using
different competing stimuli should not be compared directly. Results further
demonstrated that participants' ratings of preference for background sound were
consistent over time; however, listeners' preference for background sound was not
related to their acceptance of background noise (i.e., ANL). This may indicate
listeners cannot accurately assess their ability to accept background sounds, at
least with the questionnaire used in the present study.
PMID- 17039767
TI - Acceptance of background noise levels in bilingual (Korean-English) listeners.
AB - The acceptable noise level (ANL) is the maximum amount of background noise that
listeners are willing to accept while listening to speech. ANL has not been
studied in listeners who use languages other than English. The purpose of this
study was to explore whether ANLs obtained from Korean listeners in both English
and Korean were comparable to ANLs obtained from monolingual English listeners.
The results showed that ANLs obtained in English (ANL-E) did not differ
significantly for the bilingual and monolingual listeners. Additionally, a cross
language comparison, within bilinguals, showed that ANLs obtained using Korean
(ANL-K) speech stimuli were not significantly different from ANL-E. Finally,
speech perception in noise did not correlate with ANLs in English or Korean for
the bilingual listeners. Results suggest that the ANL measure is language
independent within bilinguals and may be of potential clinical use in minority
language groups.
PMID- 17039768
TI - Acceptance of noise with monaural and binaural amplification.
AB - The present study investigated the effects of monaural and binaural amplification
on speech understanding in noise and acceptance of noise for 39 listeners with
hearing impairment. Results demonstrated that speech understanding in noise
improved with binaural amplification; however, acceptance of noise was not
dependent on monaural or binaural amplification for most listeners. These results
suggest that although two hearing aids maximize speech understanding ability in
noise, most individuals' acceptance of noise, which is directly related to
hearing aid use, may not be affected by the use of binaural amplification. It
should be noted that monaural amplification resulted in greater acceptance of
noise for some listeners, indicating that binaural amplification may negatively
affect some individuals' willingness to wear hearing aids. It should also be
noted that interaural differences in acceptance of noise might exist for some
listeners; therefore, if only one hearing aid is fitted, monaural ANLs should be
measured.
PMID- 17039769
TI - Differences in responses from the cochleae and central nervous systems of females
with low versus high acceptable noise levels.
AB - Studies of acceptable noise level (ANL) consistently report large intersubject
variability in acceptance of background noise while listening to speech. This
variability is not related to age, gender, hearing sensitivity, type of
background noise, speech perception in noise performance, or efferent activity of
the medial olivocochlear pathway. An exploratory study was conducted to determine
if differences in aggregate responses from the peripheral and central auditory
system can account for intersubject variability in ANL. Click-evoked otoacoustic
emissions (CEOAEs), binaural auditory brainstem responses (ABRs), and middle
latency responses (MLRs) were measured in females with normal hearing with low (n
= 6) versus high (n = 7) ANLs. Results of this preliminary study indicate no
differences between the groups for CEOAEs or waves I or III of the ABR.
Differences between the two groups emerge for the amplitudes of wave V of the ABR
and for the Na-Pa component of the MLR, suggesting that physiological variations
arising from more central regions of the auditory system may mediate background
noise acceptance.
PMID- 17039770
TI - [Advances in the study of nucleoside antiviral drugs].
PMID- 17039771
TI - [Recent advances in the study of pharmacological activities and solid-phase
synthesis of indoles and their analogues].
PMID- 17039772
TI - [Advances in the study of cardiac M3 receptor as a novel target of antiarrhythmic
drugs].
PMID- 17039773
TI - [Comparison of the inhibitory activities of salvianolic acid B and Ginkgo biloba
extract EGb 761 on neurotoxicity of beta-amyloid peptide].
AB - AIM: To compare the effects of salvianolic acid B (Sal B) and Ginkgo biloba
extract EGb 761 on beta-amyloid peptide (beta-AP) fibril formation and
cytotoxicity to PC12 cells. METHODS: The inhibitory effects of Sal B and EGb 761
on beta-AP1-40 fibril formation were determined by using fluorescence analysis
with Thioflavin T (ThT) and electron microscopic image. beta-AP25-35 was aged by
incubating at 37 degrees C for 7 d, then the protein was incubated with PC12
cells. The protective effects of Sal B and EGb 761 against cytotoxicity induced
by aged beta-AP25-35 in PC12 cells were evaluated by MTT reduction assay and flow
cytometric analysis. beta-AP25-35-induced accumulation of intracellular reactive
oxygen species (ROS) was determined by fluorescence analysis. RESULTS: Both Sal B
and EGb 761 inhibited the formation of amyloid fibrils, protected PC12 cells from
beta-AP25-35-induced cytotoxicity, and decreased ROS accumulation caused by beta
AP25-35. The effective doses of Sal B were far lower than those of EGb 761.
CONCLUSION: Sal B was much more efficient than EGb 761 in inhibiting beta-AP
aggregation and in protecting PC12 cells from beta-AP-induced cytotoxicity.
PMID- 17039774
TI - [Effect of inducible nitric oxide synthase on tumour cells sensitivity to
mitomycin C analogue 629 in vitro].
AB - AIM: To examine the effect of inducible nitric oxide synthase (iNOS) on tumour
cells chemosensitivity to mitomycin C (MMC) analogue 5-aziridinyl-3-hydroxyl-1
methylindole-4,7-dione (629) in vitro, and elucidate the possible role of iNOS in
the metabolism of 629. METHODS: Human sarcoma cells (HT1080) and its iNOS gene
transfected clones (iNOS9, iNOS12) were exposed to 629 at concentrations of 1
nmol x L(-1) - 100 micromol x L(-1). 3-[4, 5-Dimethylthiazol-2-yl] -2,5
diphenyltetrazolium bromide (MTT) assay, agarose electrophoresis and flow
cytometric analysis were used to determine cell sensitivity, deoxyribonucleic
acid (DNA) damage and the change of cell cycle in above process, respectively.
All experiments were performed both in air and under hypoxia parallelly. RESULTS:
629 was more toxic than MMC, and enhanced cytotoxicity under hypoxia, which
resulted in cell necrosis. Sixteen hours after treated with 629, HT1080 cells and
related iNOS-transfected clone cells were obviously blocked in G2/M phase.
CONCLUSION: iNOS plays dual roles in 629 metabolism, enhancing or decreasing the
cytoxicity of 629 depending on the intracellular oxygen pressure P(O2), which
caused higher cytotoxicity to hypoxia cells of 629 with the increasing of iNOS
activity.
PMID- 17039775
TI - [Action of AMP579 and adenosine on potassium or sodium ionic channels in isolated
rat and guinea pig ventricular myocytes].
AB - AIM: To study the effect of AMP579 and adenosine on potassium ionic (K+) or
sodium ionic (Na+) channels and to elucidate ionic mechanisms underlying negative
inotropic and antiarrhythmic effects of AMP579 and adenosine. METHODS: Ionic
channel currents of rat and guinea pig ventricular myocytes were recorded by
patch clamp technique in whole-cell configuration. RESULTS: Adenosine showed a
stronger activating effect on transient outward K+ current (I(to)) than AMP579,
EC50 of adenosine and AMP579 were 2.33 and 8. 32 micromol x L(-1), respectively
(P < 0.05). An adenosine A1 receptor blocker, 1,3-dipropyl-8-cyclopentylxanthine
(PD116948), can abolish the effects of AMP579 and adenosine on I(to),
demonstrating that the effect is mediated by adenosine A1 receptor. Adenosine
exerted a more obvious inhibitory effect on delayed rectifier K+ current (IK)
than AMP579. IC50 of adenosine and AMP579 were 1.21 and 2.31 micromol x L(-1),
respectively (P < 0.05). AMP579 had a more powerful inhibitory effect on inward
rectifier K+ current (IK1) than adenosine. IC50 of AMP579 and adenosine were 4.15
and 20.7 micromol x L(-1), repectively (P < 0.01). AMP579 and adenosine exerted a
similar inhibitory effect on fast inward Na+ current (INA), IC50 of AMP579 and
adenosine were 9.46 and 6.23 micromol x L(-1), respectively (P > 0.05).
CONCLUSION: Adenosine showed a stronger activating effect on I(to) than AMP579,
however, the mechanism of AMP579 and adenosine activating I(to) was mediated by
adenosine A1 receptor. AMP579 has a more powerful inhibitory effect on IK1, and
less inhibitory effect on IK than adenosine. Both drugs have a similar inhibitory
effect on INa. The negative inotropic and antiarrhythmic effects are related to
these ionic mechanisms.
PMID- 17039776
TI - [Establishment of a reporter gene-based cell screening model for discovering new
agonists of estrogen receptor beta subtype].
AB - AIM: To establish a sensitive and efficient reporter gene-based screening model
for finding agonists of estrogen receptor beta subtype. METHODS: A recombinant
vector pTAL-ERE-SEAP was constructed by inserting a synthetic sequence composed
of five estrogen responsive elements in front of promoter of pTAL-SEAP vector.
pTAL-ERE-SEAP was then transfected into human embryonic kidney (HEK293) cells.
G418 (200 microg x mL(-1)) was added to select positive clones that can be
induced by E2 to express reporter gene SEAP. The speciality was tested by several
ligands of relative nuclear receptors of the same family. The stability of the
model, the time-effect relationship, the dose-response relationship, and the
immunocytochemistry staining of ERbeta expression after transfection were
observed. 2 622 compounds were screened by using this model. RESULTS: Stably
transfected clones were obtained. The expression levels of reporter gene SEAP of
positive clones was induced by E2 in a dose-response and time-effect relationship
manners. The Z' factor value was 0.7. The expression levels of dexamethasone and
other ligands were low. The result of immunocytochemistry staining showed the
expression of ERbeta. E2 had no proliferating effects on stably transfected
clones. CONCLUSION: Stably transfected positive clones transfected with
recombinant vector pTAL-ERE-SEAP were obtained. The positive clones may be used
to screen for agonists of estrogen receptor beta subtype by measurement of
luminescent value of expressed SEAP in wells of microlitre plate.
PMID- 17039777
TI - [The design and synthesis of 2-aminothiazole derivatives and their inhibitory
activity on apoptosis].
AB - AIM: To investigate the inhibitory effect of 2-aminothiazole derivatives on Neuro
cell apoptosis and QSAR. METHODS: The 2-aminothiazole derivatives were designed
and synthesized based on the lead compound of PFT-alpha, the protective action of
the compounds I and II against and their inhibitory action on PC12 cell apoptosis
induced by H2O2 were determined by MTT method and FCM method. The QSAR equation
was obtained from Cerius2-QSAR+ module. RESULTS: Eleven novel 2-aminothiazole
Schiff base compounds (II) have been designed and synthesized. The structure of
the compound II were characterized by IR, MS,1H NMR, 13C NMR. Their protective
action against and the inhibitory action on PC12 cell apoptosis induced by H2O2
were found in this experiment. The optimal QSAR equation obtained from the
Cerius2-QSAR+ module by using log (1/EC50) with corresponding descriptors is
Activity = 6.947 68 - 0.088 72 x "LUMO" - 0.043 018 x "Alogp98" - 0.128 752 x
"Rad0fGration" + 0.018 246 x "Dipole-mag". The correlation statistics parameters
of the above equation are as follows: r2 = 0.970, F-test = 49. 149, r = 0. 985
and Lse = 0. 001. CONCLUSION: The 2-aminothiazole derivatives exhibited certain
activity in inhibiting PC12 cell apoptosis induced by H2O2. Some compounds such
as I-6, I-9 and II-6 have the dual activities, the protective action against and
inhibitory action on PC12 cell apoptosis induced by H2O2. The QSAR equation
indicated that it is favorable for enhance the activity of 2-aminothiazole
derivatives by the reduction of "radius of gyration" and the energy of "LUMO" of
the compounds.
PMID- 17039778
TI - [Chemical constituents of Knoxia valerianoides].
AB - AIM: To study the chemical constituents of Knoxia valerianoides Thorel et Pitard.
METHODS: Chromatographic methods were used for the isolation and purification.
Structures were elucidated on the basis of chemical analysis and spectroscopic
data. RESULTS: Three anthraguinones were isolated from K. valerianoides and
identified as 1, 3, 5-trihydroxy-2-methyl-6-methoxyl-anthraguinone (kaoxiadin,
I), 1, 3, 6-trihydroxy-5-ethoxylmethyl-anthraguinone (II) and 1, 3-dihydroxy-2
methylanthraguinone (rubiadin, III). CONCLUSION: Compound II is a new
anthraguinone constituent.
PMID- 17039779
TI - Water-soluble phenolic glycosides from the whole plant of Bulbophyllum
odoratissimum.
AB - AIM: To investigate the water-soluble phenolic glycosides from the whole plant of
Bulbophyllum odoratissimum. METHODS: Column chromatography techniques were used
to isolate the chemical constituents, physico-chemical constants and
spectroscopic analysis were employed for structural elucidation. RESULTS:
Bulbophyllinoside (1), a new phenolic glycoside and three known compounds were
isolated from the whole plant of Bulbophyllum odoratissimum Lindl. Their
structures were determined as 3-hydroxyphenethyl alcohol 4-O-( 6'-O-beta
apiofuranosyl) -beta-D-glucopyranoside (1), 3-methoxyphenethyl alcohol 4-O-beta-D
glucopynanoside (2), 3, 5-dimethoxyphenethyl alcohol 4-O-alpha-D-glucopynanoside
(3) and syringin (4). CONCLUSION: Bulbophyllinoside (1) is a new compound.
PMID- 17039780
TI - [Determination of ginsenoside Rd and its metabolites in rat urine by LC-MS].
AB - AIM: To study the metabolic pathways of ginsenoside Rd in rats. METHODS: Urine
samples were collected before and after 24 h of single oral administration of 150
mg and intravenous administration of 60 mg of ginsenoside Rd to six rats,
separately. The samples were purified by SPE column and then were analyzed by
liquid chromatography-ESI-mass spectrometry for putative metabolites. RESULTS:
Parent drug and its seven metabolites were identified in rat urine based on
comparing total ion chromatograms of the blank with the metalolic urine as well
as mass spectra. Its main metabolic pathways and possible structures are
elucidated. CONCLUSION: Oxidation, combination and deglucosylation were found to
be the major metabolic pathway of ginsenoside Rd in rats.
PMID- 17039781
TI - [RP-HPLC fingerprint for quality assessment of Radix Angelicae dahuricae].
AB - AIM: To establish the RP-HPLC fingerprint analysis for the quality control of
Radix Angelicae dahuricae. METHODS: HPLC fingerprint analysis method of Radix
Angelicae dahuricae was developed. Kromasil C18 column (250 mm x 4.6 mm ID, 5
microm) was used, with mixture of acetonitrile and water as mobile phase in a
gradient mode. The flow rate was 1.0 mL x min(-1). The wavelength of measurement
was 254 nm. Twenty-one batches of Radix Angelicae dahuricae were determined.
RESULTS: The 21 samples were classified as 4 clusters by cluster analysis and the
11 superior in producing area samples were confirmed to establish the mutual
model. The samples' quality was assessed by Similarity Evaluation System for
Chromatographic Fingerprint of TCM 2004. CONCLUSION: The method can be used to
identify and evaluate the quality of Radix Angelicae dahuricae conveniently.
PMID- 17039782
TI - [Biliary excretion of genistein and its metabolite at different doses in rats].
AB - AIM: To study the biliary excretion of genistein and its metabolite at different
doses in rats. METHODS: Suspended in 0.5% CMC-Na solution, genistein was orally
administered to rats at the dose of 6.25, 12.5 and 50 mg x kg(-1), separately. At
various time intervals, the bile was collected. The bile was treated with beta
glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL
mixture of methyl tert-tubtyl ether and pentane (8:2). The organic phase was
removed into the tubes and then evaporated in ventilation cabinet. The residue
was dissolved in 50 microL of methanol. Twenty microL solution was drawn and
detected by high-performance liquid chromatography. RESULTS: The accumulative
biliary excretion of genistein was (42.56 +/- 6.54) , (75.17 +/- 18.87) and
(126.60 +/- 34.78) microg at the dose of 6.25, 12.5 and 50 mg x kg(-1),
respectively. The total drug (genistein plus glucuronidated genistein) excreted
from bile was (108.46 +/- 35.23), (423.46 +/- 158.31) and ( 853.74 +/- 320. 84)
microg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85.17%
at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. CONCLUSION: The
genistein was excreted mainly in the form of glucuronidated genistein in rat
bile. The genistein and glucuronidated genistein were excreted in a nonlinear
dose-dependent manner.
PMID- 17039783
TI - [Peptide mapping analysis of recombinant human interleukin-11 with HPLC-ESI-Q
TOF/MS spectrometry].
AB - AIM: To analyze the peptide mapping of recombinant human interleukin-11 (rhIL-11)
by HPLC-ESI-Q-TOF/MS spectrometry. METHODS: The trypsin digested rhIL-11 at 37
degrees C over night, and the peptide mapping was performed by HPLC. The relative
molecular weight of the peptides fragments was measured by ESI-Q-TOF/MS, and
amino acid sequence was analyzed by MS/MS. RESULTS: The peptide fragments of rhIL
11 in the peptide mapping were assigned by analyzing the retain time, relative
molecular weight and amino acid sequence. And 97% of the expected peptides were
detected in this way. CONCLUSION: The study proves that HPLC-ESI-Q-TOF/MS is a
good method to analyze peptide mapping of protein with the advantage of
sensitivity, high speed and accuracy.
PMID- 17039784
TI - [Preparation, characterization, and pulmonary delivery of rifapentine liposomes
modified by lauric diethanolamide].
AB - AIM: To prepare rifapentine (RIF) liposomes modified by surfactants for studying
their the water-solubility, drug loading effeciency, release rate and pulmonary
drug delivery. METHODS: The film method was used to prepare RIF liposomes. Of
verious RIF liposomes morphology by lauric diethanolamide (LDEA), Tween 80 and
azone, the properties were studied, envolving morphology, entrapment drug release
rate and dissected lung-membrance penetration rate of swine. Pulmonary delivery
study was carried out through bronchoscope. RESULTS: The particle size of RIF
LDEA liposomes was between 15 - 50 nm. The top entrapment efficiency reached
83.0%. The apparent coefficient of membrane penetration (Kp) was 44.29. LD50 was
675 mg x kg(-1) by iv. CONCLUSION: LDEA increased the water-solubility, loading
effeciency and release rate of RIF liposomes. The prepared RIF-LDEA liposomes
were suitable for the treatment of pulmonary tubrculosis through bronchoscope.
PMID- 17039785
TI - [Preparation of verapamil hydrochloride controlled-onset extended-release pellets
and its pharmacokinetics in dogs].
AB - AIM: To prepare verapamil hydrochloride controlled-onset extended-release pellets
(VH-COERP) and study its release behavior in vitro. To compare the
pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral
administration of VH-COERP and verapamil hydrochloride delayed-release pellets
(VH-DRP) as reference. METHODS: The core of VH-COERP were prepared in the
fluidized bed (mini-glatt) by spraying water solution containing drugs onto
sucrose-starch pellets with hydroroxy propyl methyl cellulose (HPMC) as the inner
coating swelling layer and ethylcellulouse aqueous dispersion as the outer
coating controlled layer. Through modifying the coating level of inner and outer
layer, the VH-COERP with the optimized cumulative release profile was obtained.
The concentration of VH in plasma of six dogs and its pharmacokinetic behaviors
after oral administration of VH-COERP and VH-DRP at different times were studied
by RP-HPLC. The pharmacokinetic parameters were computed by software program
3P97. RESULTS: The lag time, the release behavior and the amount of VH from VH
COERP within 24 hours were not influenced by the pH of dissolution medium and
post-process, but obviously influenced by the different kinds of added material
in swelling layer and the coating level of the inner swelling layer and the outer
controlled layer. In vitro the lag time of release profile of VH from VH-COERP
was 5 h and then VH was extended release from VH-COERP in the following time.
Compared with the VH-DRP, VH-COERP in vivo has an obviously lag time (4 h) , Tmax
was also delayed (8 h) and the relative bioavailability was (94.56 +/- 7.64)%.
CONCLUSION: The release profile of VH from VH-COERP was shown to be extended
release after an conspicuous lag time in vitro and in vivo. So the drug can be
taken by the patient before bed time and begin to work at the morning.
PMID- 17039786
TI - [Effects of D-limonene and L-limonene on transdermal absorption of ligustrazine
hydrochloride].
AB - AIM: To investigate the effects and permeation mechanism of D-limonene and L
limonene on transdermal delivery of ligustrazine hydrochloride (LH). METHODS:
Transdermal flux of LH through porcine skin was determined in vitro by Franz-type
diffusion cells. The peak shift and peak areas of C-H stretching vibration
absorption were estimated by Fourier transform-infrared (FTIR). Morphological
changes in the stratum corneum (SC) treated with enhancers were observed by a
scanning electron microscope (SEM) and apparent density, a new concept, was
proposed to estimate the desquamated extent of SC for the first time. RESULTS:
There were no statistic difference (P > 0.05) between the transdermal fluxs of
the enantiomer enhancers which were higher than those of control and azone. But
the lag time of L-limonene was 2.55 times than that of D-limonene. The FTIR
results revealed that the shift and decreased peak area of C-H stretching
vibrations in the SC lipids were dependent on the enhancers. The enantiomers
permeation enhancers, D-limonene and L-limonene, were able to perturb and extract
the SC lipids to different extent. The disordering and extracting lipids activity
of L-limonene was stronger than that of D-limonene. SEM studies demonstrated that
the extraction of lipids was depended on the selected penetration promoters.
CONCLUSION: D-limonene was the most effective enhancer which had the greater
transdermal flux of LH and the least lag time. The results showed that the
permeation enhancement mechanism of the enantiomer enhancers to LH was multiple
ones including disordering and extracting the SC lipids and probably including
stereoselective mechanism.
PMID- 17039787
TI - [Pharmacokinetics of doxorubicin alginate microspheres and evaluation of its
hepatic arterial embolization in vivo].
AB - AIM: To investigate the pharmacokinetics of doxorubicin alginate microspheres
(DOX-AM) in vivo after hepatic arterial embolization. METHODS: China miniature
pigs were chosen as the experimental animals. Transcatheter hepatic arterial
chemoembolization (TACE) with DOX-AM (experimental group), lipiodol and DOX (DOX
lipiodol, control group 1), and infusion with DOX (control group 2) were
performed after angiography and superselection of an intrahepatic branch of
hepatic artery. After chemoembolization or infusion, the blood was collected at
different time intervals. Drug concentration in plasma was measured by HLPC and
the parameters of pharmacokinetics were calculated. RESULTS: The values of T1/2,
AUC, Cmax, and MRT of the DOX-AM were significantly different from those of
control group 1 and control group 2. After embolization, the DOX-AM embolized in
the vessel and still retained there at 8 weeks. The digital subtraction
arteriography (DSA) and computerized tomography (CT) showed the reliable
embolization results. The histological examination indicated that the liver
damnifications were changed transitorily in all groups (P < 0.05) and were
recovered within two weeks. The liver damnifications increased in following
order: DOX < DOX-AM < DOX-lipiodol. CONCLUSION: DOX-AM showed definite property
of delayed release of drug in liver, and increased the retention time and
concentration of DOX after embolization in vivo.
PMID- 17039788
TI - [In vitro and in vivo assesemet of sodium norcantharidin lipid microsphere].
AB - AIM: To prepare lipid microsphere of sodium norcantharidin (NCTD) and then study
their characters and pharmacokinetic behavior. METHODS: Dynamic Light Scattering,
HPLC and retrodialysis technique were used to determine the in vitro characters
of the NCTD loaded lipid microsphere (LM), such as the particle size, xi
potential, content, incorporation ratio, release profile and changes after
dilute. And the plasma concentration was determined by HPLC-MS, compared with
NCTD aqueous solution at the same time. RESULTS: Every property showed that the
LM was preferable. The average diameter was about 200 nm. The xi-potential was -
38 mV. The content was close to 100%. And the incorporation ratio exceeded 80%.
After i. v. administration of single dose, the pharmacodynamic parameter of LM
AUC was 111.28 microg x mL(-1) x h(-1). The data of plasma concentrations showed
that the NCTD LM was of two compartment. There was no obvious difference between
in vivo parameters of LM and reference solution. CONCLUSION: The NCTD LM was
eligible and the character of it in vivo was not changed.
PMID- 17039789
TI - [Excretion of (-)-clausenamide in rats].
AB - AIM: To study the excretion of (-)-clausenamide in rats. METHODS: The urine,
feces and bile were collected at predetermined time points after (-)-clausenamide
was orally administrated to 6 rats (30 mg x kg(-1)). The concentrations of (-)
clausenamide and its metabolite 6-OH-(-)-clausnamide were determined by HPLC
MS/MS method using glipzide as the internal reference, and the accumulative
excretion amount of (-)-clausenamide and 6-OH-(-)-clausenamide was calculated in
the urine, feces and bile, separately. RESULTS: (-)-Clausenamide was recovered
mostly (44%) from feces in 112 hours, 7.1% was found from urine in 120 hours and
0.013% was detected from bile in 24 hours. The accumulative excretions of 6-OH-(
)-clausenamide were 0.92% , 0.46% and 0.0003% of the administered dose from
feces, urine and bile, respectively. CONCLUSION: The major amount of (-)
clausenamide was recovered from feces after (-)-clausenamide was orally
administrated to rats (30 mg kg(-1)).
PMID- 17039790
TI - [Determination of three constituents in Radix Astragali by HPLC-MS].
AB - AIM: To determine calycosin-7-O-beta-D-glucoside, astragaloside IV and
formononetin in Radix Astragali and other relative samples by HPLC-MS. METHODS:
HPLC was carried out with Agilent 1100LC/MSD, equipped with Agilent Zorbax SB C18
column (250 mm x 4.6 mm ID, 5 microm) and mass spectrum detector. The mobile
phase (CH3CN-H2O) was eluted in gradient mode. RESULTS: The calibration curves of
calycosin-7-O-beta-D-glucoside, astragaloside IV and formononetin were linear in
the range of 0.03 - 1.21 microg x mL(-1), 0.35 - 13.86 microg x mL(-1) and 0.38 -
15.22 microg x mL(-1), respectively. These recoveries of samples were from 95% to
105% with RSD less than 1.5%. CONCLUSION: The method was employed to analyse 25
samples of Radix Astragali and other relative samples, including Radix Astragali
slice, Radix Astragali Preparata, Hedysarum polybotrys Hand. -Mazz, Astragalus
ernestii Comb. The contents of three constituents vary greatly because of the
species, place of collection and season of harvesting. This method could apply to
evaluate the quality of Radix Astragali and it is simple, sensitive and reliable.
PMID- 17039791
TI - [Antitumor effects of nobiletin on Heps and its mechanism].
AB - AIM: To study the inhibitory effect and mechanism of nobiletin on Heps tumor
bearing mice. METHODS: Models of Heps tumor bearing mice were established. The
inhibitory rates of tumor growth were calculated, the apoptosis morphology of
tumor tissue was observed. The T lymphocyte transformation capacity was tested by
MTT assay, the TNFalpha and IL-2 production were measured by LDH kits. RESULTS:
Nobiletin could significantly inhibit Heps tumor growth. The inhibitory rates
were 42.14% - 65.09% (P < 0.01). The morphology of tumor tissues in nobiletin
group had typical characters of necrosis and apoptosis through transmission
electron microscope. Nobiletin could stimulate T lymphocyte transformation and
the production of TNFalpha and IL-2. CONCLUSION: Nobiletin has obvious antitumor
effect on Heps, the main mechanism is to enhance the cellular immune function and
induce apoptosis of tumor tissue.
PMID- 17039793
TI - [Some usual definitions in the article of the middle ear surgery].
PMID- 17039792
TI - [Recognition of chronic otitis media and mastoiditis].
PMID- 17039794
TI - [Relationship between the content of fibrinogen in middle ear effusion and the
effect of treatment on secretory otitis media].
AB - OBJECTIVE: To study the relationship between the fibrinogen content in middle ear
effusion (MEE) and the protracted inflammation of secretory otitis media (SOM)
and to explore the possible mechanism of batroxobin in treatment of SOM. METHODS:
The fibrinogen content of middle ear effusion from 156 patients with SOM was
investigated with concretion technique at different stages. After two times
punctuation of tympanum, the recurrence patients were randomly divided into two
groups: batroxobin and dexamethasone group, and 0.5 ml (2 BU/ml) batroxobin or
dexamethasone (2 mg/ml) was injected into middle ear cavity. The therapeutic
effects were investigated. RESULTS: The concentration of fibrinogen in the
recurrence group of SOM patients was higher than that in the cured group, and
even higher in the second recurrence group than in the first recurrence group (P
< 0.01). There was significantly different (P < 0.001) in the therapeutic
efficacy between the batroxobin group (91.6%) and the dexamethasone group (62.
5%); the difference of the fibrinogen content in MEE and air conduction of pure
tone audiometry at frequencies (0.5, 1.0, 2.0 kHz) between the two groups after
treatment were also significant (P < 0.01). CONCLUSIONS: Fibrinogen may play a
significant role in the occurrence and development of secretory otitis media.
Batroxobin had better therapeutic effect on SOM than dexamethasone. The mechanism
of batroxobin in the treatment of SOM may be that the batroxobin can relief the
depressant effect of fibrinogen on surface active agents of the Eustachian tube
and prevent the fibrinogen from turning into insoluble fibrin polymer by means of
fibrinolysis.
PMID- 17039795
TI - [Preparation of new protein carrier of vaccine against pneumococcal otitis media
with genetic engineering technology].
AB - OBJECTIVE: To prepare pneumolysin as a new protein carrier of vaccine against
otitis media with genetic engineering technology and establish the base of the
study on pneumococcal conjugative vaccines. METHODS: Genomic DNA was isolated
from streptococcus pneumoniae. A pair of primers which included two restriction
sites was designed based on the published pneumolysin gene sequence. The
pneumolysin gene was amplified from pneumococcal DNA with PCR technology. The
restriction enzyme digested fragment was linked into the cloning vector PET-28a
and the recombinant plasmid DNA containing pneumolysin was then transfected into
host cell E. coli JM109 (DE3). RESULTS: DNA fragments were subcloned to construct
the complete pneumolysin gene by a conventional coning and PCR. The inserted
pneumolysin gene sequence was confirmed by DNA sequencing and the pneumolysin
protein was successfully expressed. The relative molecular mass of the expressed
product was 52 000. The expressed product amounted to 8% of the total host cell
protein. CONCLUSIONS: The pneumolysin gene was successfully cloned into host cell
using genetic engineering technology. The recombinant pneumolysin was expressed
and purified for preparation. This work laid a foundation of the preparation of
pneumococcal conjugative vaccines.
PMID- 17039796
TI - [Immunohistochemical discrimination of aggressivity between the cholesteatoma
from different positions].
AB - OBJECTIVE: To investigate whether the cholesteatoma from different positions have
different biological characteristics. METHODS: The expression of the Ki-67 and
collagen IV in 19 specimens of cholesteatoma were stained immunohistochemically
using the SP method, according to the origin of the specimens, include 7 cases
from the epitympanum, 8 cases from tympanic sinus and 4 cases from the out
acoustic canal. According to the severity of the inflammation in the perimatrix,
the inflammation group included 7 cases, the non-inflammation group included 8
cases. RESULTS: The average count was the same between the cholesteatoma from
epitympanum and tympanic sinus. And the count of the cholesteatoma in the middle
ear was also the same to the cholesteatoma from the out acoustic canal. But even
from the same sample, the cholesteatoma from the positions with severe
inflammation in the perimatrix count much higher, and the difference was
statistically significant. Collagen IV had been found to localized in the basic
membrane. In some specimens the staining of the collagen IV was not continuous.
CONCLUSIONS: The results suggested that it was the severity of inflammation in
the perimatrix influenced the differences, but not the origins of the
cholesteatoma.
PMID- 17039797
TI - [Endoscopic surgery for nasopharyngeal angiofibroma].
AB - OBJECTIVE: To investigate the efficacy and the surgical techniques of transnasal
endoscopic procedure for juvenile nasopharyngeal angiofibroma (JNA). METHODS:
Twenty-one nasopharyngeal angiofibroma patients were treated using transnasal
endoscopic approach. They were divided into group A (without intracranial
extension) and group B (minimal intracranial extension) according to the staging
of Sessions. The patients were treated mostly with endoscopic surgery. In two
midfacial operations cases, endoscopy was also used. The staging, average blood
loss during surgery, tumor residual, and (or) recurrent tumor were evaluated.
RESULTS: Group A (19 cases) had an average blood loss of 1000 ml. Nineteen
patients had no residual or recurrent tumor over a follow-up of 8-24 months.
Group B (2 cases) had an average blood loss of 1500 ml. One of the patients had
minimal residual tumor around the cavernous sinus, but showed no progression over
a follow-up of 2 years. Another patient had no residual or recurrent tumor over a
follow-up of 8 months. CONCLUSIONS: The data suggests that transnasal endoscopic
surgical techniques can be used to treat JNA which either limited to nasal and
nasopharyngeal cavities or and the tumor with sphenoid and ethmoid invasions and
even minimal intracranial extension.
PMID- 17039798
TI - [Effects of ephedrine on human nasal cilia movement measured with high-speed
digital microscopy].
AB - OBJECTIVE: To investigate the effects of ephedrine on human nasal cilia movement.
METHODS: Ciliary beat frequency (CBF) of cultured human nasal epithelial cells
was measured by high-speed digital microscopy in HBSS and ephedrine solution of
different concentrations in 10 minutes. RESULTS: CBF of cultured nasal epithelial
cells exposed to HBSS showed no significant changes in 10 minutes. However, in
2.5 g/L , 5 g/L, 10 g/L and 20 g/L ephedrine solution, CBF increased
significantly in 1-2 minutes and reached the apex, then it decreased gradually,
at the 10th minute. CBF of the samples exposed to 2.5 g/L and 5 g/L ephedrine
solution were slower than those in HBSS, but no significant changes were found.
However, in 10 g/L and 20 g/L ephedrine solution, CBF decreased significantly
when compared with samples in sHBSS. With the concentrations from 2.5 g/L to 20
g/L ephedrine, the increment was independent on the concentration, the inhibitory
effect was dependent on the concentration. CONCLUSIONS: In initial time, 2. 5 g/L
20 g/L ephedrine stimulated CBF, then 10 g/L-20 g/L ephedrine inhibited CBF. The
stimulation of 2.5 g/L and 5 g/L ephedrine on CBF was longer than that of 10 g/L
and 20 g/L ephedrine. 5 g/L ephedrine had maximum stimulatory effect without
obvious inhibitory effect on cultured human nasal CBF.
PMID- 17039800
TI - [Autologous transplantation of fascia into the vocal fold for sulcus vocalis].
AB - OBJECTIVE: To evaluate the effects of vocal fold autologous fascia
transplantation for treating sulcus vocalis. METHODS: Sulcus vocalis among 23
cases were dissected and vocal fold autologous fascia transplantation performed.
For type III sulcus associated with thyroarytenoid muscle atrophy, autologous fat
injection was carried out also. The voice acoustic quality and video
laryngostroboscopic data were evaluated before and after surgery. RESULTS: Among
23 patients, 4 were excluded from the analysis because of failure of surgery or
lost to follow-up, leaving a total of 19 patients who were included in the
analysis. Until 6-8 weeks after surgery, patients could start to phonate. Vocal
quality became better 3 months postoperatively. Vocal quality became steady 6
months after the surgery. Vocal improvement was obtained in 89. 5% (17/19) of the
patients. The shapes, glottal closures and mucosal waves of vocal folds were
improved. There was a significant decrease (improvement) in scales of grading,
roughness, breathiness, and asthenic after surgery (P < 0.05). For the grade
parameter, it improved 2 scales in 2 patients (10.5%) and 1 scale in 15 patients
(79.0%). Acoustic analysis and maximum phonation time (MPT) were significantly
improved after surgery (P < 0.01). Acoustic parameters of 42.0% (8/19) patients
returned to normal range. MPT of 17 patients (89.5%) was in normal scopes. With 6
to 24 months follow-up, vocal function was steadily. There was no apparent
reabsorption. CONCLUSIONS: Autologous transplantation of fascia into the vocal
fold was a useful and safe procedure for pathological sulcus vocalis.
PMID- 17039799
TI - [Free anterolateral thigh flap for repairing the defects of oral cavity and
maxillofacial].
AB - OBJECTIVE: To investigate the outcomes following the tumor resection of oral
cavity and maxillofacial and reconstruction with free anterolateral thigh flaps
(ALT). METHODS: Thirty one patients underwent ALT reconstruction following the
tumor resection from Dec. 2004 to Dec. 2005. Among them, 17 cases were squamous
cell carcinoma (SCC) of tongue, 6 cases of buccal SCC and 8 other malignant. The
size of the ALT flaps ranged from 4 to 8 cm in width and 6 to 23 cm in length.
Tracheotomy were performed for 4 cases intraoperatively. RESULTS: The overall
successful rate was 96.8%. Thirty cases survival no cancer, 1 case died of
recurrent and no-controlled of lymph-node in 8 months after operation.
Postoperative vessel thrombosis occurred in 3 flaps between 12 hours to 4 days
after operation. Two of them were saved. The necrosis area of the third flap was
25%. CONCLUSIONS: The ALT was benefit to repair the defects of oral cavity and
maxillofacial, and the donor place was more easily hidden and didn't not
influence the outlook and function; the important normal functional framing such
as teeth and bone should be preserved; the pedicle of vessel could't be twisted
during the procedure of reconstruction to avoid vein oppressed; the size of flap
should be suitable to defects in order to avoid flaps being crowd and blood clot;
tracheotomy was safe while repairing the defect of hard and soft palate.
Reconstructive surgical procedures;
PMID- 17039801
TI - [Surgical treatment of hyperthyroidism].
AB - OBJECTIVE: In order to explore the management of peri-operation and the
therapeutic effect in the surgical treatment of hyperthyroidism. METHODS: Fifty
five cases of hyperthyroidism were undergone near-total thyroidectomy, during the
operation recurrent laryngeal nerve was exposed, and the parathyroid was found
with microscope when necessary. The third rank of inferior thyroid arteries were
ligated to guarantee the blood supply for parathyroid. RESULTS: All cases
underwent near-total thyroidectomy. There was no mortality, and no permanent
recurrent laryngeal nerve palsy occurred, and no permanent hypoparathyroidism,
and no recurrent hyperthyroidism. Follow-up was carried out 16 months to
approximately 5 years after near-total thyroidectomy patients, Hypothyroidism
occurred in 15 cases (57.7%), serum calcium levels were 2.15-2.45 mmol/L.
CONCLUSIONS: Special attention should be given to the management of peri
operation, the above the method can prevent operative complication in the
surgical treatment of hyperthyroidism, with excellent result.
PMID- 17039802
TI - [Distribution of cervical lymph node metastasis in well-differentiated thyroid
carcinoma].
AB - OBJECTIVE: To study the distribution of cervical lymph nodes metastases in
patients with differentiated thyroid carcinoma, explore the surgical modality of
the neck of cN + cervical node metastasis and evaluate the role of preoperative
ultrasonography in detecting of cervical metastases of differentiated thyroid
carcinoma. METHODS: Data were reviewed retrospectively from medical records
between July 2003 and July 2005, in which 93 patients (113 sides) of
differentiated thyroid carcinoma patients with cN + cervical lymph nodes
metastasis. Patients were divided into 2 groups: group 1, 64 cervical sides with
preoperative palpable cervical lymph nodes; group 2, 49 cervical sides with
impalpable node but preoperative ultrasonic positive nodal metastasis. All the
pathologic specimens were reviewed by pathologists counting the numbers of
pathologic positive nodes and mapping localization of positive nodes in level II,
III, IV, V and VI respectively. RESULTS: In 93 patients 21.5% (20/93) of those
metastasize bilaterally. In those 113 sides specimens 92 sides (81.4%) involved
multi-sites in the neck. The distribution of metastasized nodes were; level II,
60.2% (68/113); level III, 70.8% (80/113); level IV,61.9% (70/113); level VI,
58.4% (66/113); level V, 22.5% (25/113). The numbers of positive nodes of group 1
were more than the number of group 2 (10.1 vs 6.9) and the involved levels of
group 1 was also more than the levels of group 2 (3.18 level vs 2.61 level).
Preoperative ultrasonography could detect 43.4% (49/113) of lymph nodes
metastasis that were missed by palpation in the physical examination.
CONCLUSIONS: The distribution of the cervical nodes in patients with
differentiated thyroid carcinoma were multi-levels in the neck and mainly
localized in level II , level III, level IV and level VI. Preoperative
ultrasonography is a mainstay in detecting of cervical lymph nodes metastasis in
thyroid cancer. For patients with differentiated thyroid carcinoma of cN +
cervical lymph nodes should be undergone modified neck dissection, includes level
II, III, IV, V, VI.
PMID- 17039803
TI - [Experimental study on facial nerve regeneration by porous silk fibroin conduit].
AB - OBJECTIVE: To evaluate the feasibility of using polyporus silk fibroin as a kind
of novel material for facial nerve regeneration. METHODS: The porous silk fibroin
conduit was used in the reconstruction of a 5 mm facial nerve gap of SD rat.
Chitosan conduit was taken as control group. General observation,
electrophysiological study, histological study and image analysis were performed
2, 4, 6 and 8 weeks postoperatively. RESULTS: The facial nerve of SD rat
regenerated successfully as time passed through. Mean CAP percentage of
regenerated nerve in SF conduit was 24.94% +/- 5.73% 8 weeks postoperatively,
which had no statistical significance with that of chitosan conduit group (P =
1.125). And the average number of myelinated myelinated nerve fibers in SF
conduit was 62. 5 +/- 6. 3, which had statistical significance with that in
chitosan conduit group (P = 0.016). CONCLUSIONS: The porous silk fibroin conduit
could effectively repair facial nerve defect and improve peripheral nerve
functional recovery.
PMID- 17039804
TI - [Effects of anti-cancer bioactive peptide on cell cycle in human nasopharyngeal
carcinoma strain CNE].
AB - OBJECTIVE: To investigate effects of two kinds of anti-cancer bioactive peptide
(ACBP) on proliferation and cell cycle in human nasopharyngeal carcinoma strain
CNE. METHODS: Cell culture was used in vitro, CNE cells were exposed to different
concentration ACBP, in all groups, contrast groups were set up. And 24, 48, 72
hours later, growth characteristics of CNE cells were studied by morphological
observation and MTT assay . Cell cycle and apoptosis were analyzed by flow
cytometry (FCM). RESULTS: In normal contrast group, CNE cells grew intensively
and contacted with each other. However, cells which were treated with ACBP were
inhibitory greatly in higher dose ACBP group, necrosis could be found. MTT assay
showed that ACBP inhibited growth of CNE cell. FCM showed that ACBP (20.0
microg/ml) could raise cell ratio of S phase and induce apoptosis of CNE cells.
CNE cells were treated by two kind of ACBP (5.0 microg/ml) for 24 h, FCM showed
that early apoptosis rate were (11.8 +/- 0.3)% and (8.1 +/- 0.2)% respectively,
which showed statistical significance in comparison with control group (t =
42.535, 47.300 respectively, P = 0.000). Under light microscope, some sings of
cell apoptosis including coagulation of chromatin, fragmentation of nuclei and
apoptotic body could be found. CONCLUSIONS: Two kinds of ACBP inhibited human
nasopharyngeal carcinoma strain CNE proliferation and arrested the cells to S
phase, also induced the cells to apoptosis. Nasopharyngeal neoplasms;
PMID- 17039805
TI - [Apoptosis in nasopharyngeal carcinoma cell line NCE induced by curcumin and its
molecular mechanism].
AB - OBJECTIVE: To investigate the mechanism underlying the curcumin-induced apoptosis
of nasopharyngeal carcinoma (NPC) cell line NCE cells. METHODS: The
characteristics of apoptosis were identified by observation acridine orange and
ethidium bromide stains, ultrastructure assay, DNA fragmentation assay and TdT
mediated dUTP nick end labeling method (TUNEL). Mitochondrial membrane potential
(delta psi m), activity of caspase-3, cytosol cytochrome C and expression of gene
Fas were determined by flow cytometry (FCM), Western Blot and reverse
transcription-polymerase chain reaction (RT-PCR). RESULTS: Several evidences of
apoptosis were obtained from curcumin-treated NCE cells by acridine orange and
ethidium bromide stains, ultrastructure identification, DNA fragmentation assay
and TUNEL staining. And the mean TUNEL-positive rates increased significantly at
the 3 different time points (12 h, 24 h and 48 h; 25.6%, 40.3% and 54.5%,
respectively). In the curcumin-treated-groups, delta psi m altered significantly
and the positive rates increased in a time-dependent manner. At the 3 different
time points, the mean positive rates were 26.8%, 42.3% and 68.2%, respectively.
When caspase-3 activity was detected, 80.5% cells presented proteases activities
after 12 h incubation with curcumin. Western Blot analysis showed that
cytoplasmic cytochrome C increased significantly after incubation with curcumin.
Flow cytometry and RT-PCR analysis showed that curcumin could up-regulate the Fas
expression in time-depended manner , the positive rates of Fas protein increased
from 33.6% to 89.9%. CONCLUSIONS: Curcumin induced apoptosis of NCE cells both
through mitochondria-dependent pathway and death receptor pathway.
PMID- 17039806
TI - [Inhibitory effects of small interfering RNA specific to protein kinase CK2a on
the growth of laryngeal carcinoma cells].
AB - OBJECTIVE: To assess the effect of small interfering RNA (siRNA) specific to
protein kinase CK2a on proliferation and apoptosis of Hep-2 cell line. METHODS:
siRNA expression plasmid psiRNA-hH1neo-CK2 specific to protein kinase CK2a and
non-specific siRNA expression plasmid psiRNA-hH1neo-cont were constructed
respectively, and then were transfected into Hep-2 cells by lipofectamine
methods. Protein kinase CK2a mRNA and protein of the transfected cells were
detected by reverse transcription polymerase chain reaction (RT-PCR) and Western
Blot, respectively. Proliferation and apoptosis of the transfected cells were
observed by methyl thiazolyl tetrazolium (MTT) method and flow cytometry (FCM),
respectively. RESULTS: Protein kinase CK2a mRNA and protein expressions were
significantly decreased in the cells transfected with psiRNA-hH1neo-CK2 (P <
0.05). The Hep-2 cells grew slowly after transfected with psiRNA-hH1neo-CK2(P <
0.05). Obvious subdiploid peaks were found in the cells transfected with psiRNA
hH1neo-CK2 (P < 0.05). CONCLUSIONS: siRNA expression plasmid specific to protein
kinase CK2a suppressed the protein kinase CK2a expression and the proliferation
of Hep-2, and induced apoptosis of Hep-2 cells.
PMID- 17039807
TI - [A case of primary uvular carcinoma].
PMID- 17039808
TI - [Relationship among lymphangiogenesis, vascular endothelial growth factor-C mRNA
expression and cervical lymphatic metastasis in laryngeal carcinoma].
PMID- 17039809
TI - [Expression of Glut-1 and Glut-3 in the head and neck squamous carcinoma].
PMID- 17039810
TI - [Application of the transplanting amygdalas with pedicle in the surgery of
pharynx].
PMID- 17039811
TI - [Clinical diagnosis and therapy analysis of cervical lymphadenitis in cat-scratch
disease].
PMID- 17039812
TI - [Two cases report of the full resection of communicating cranio-osteoma in the
adjacent skull to orbitonasal].
PMID- 17039813
TI - [Pathology and classification of otitis media and early surgical treatment].
PMID- 17039814
TI - [Diagnosis of otitis media with effusion in infants].
PMID- 17039815
TI - [Preoperational evaluation of the feasibility of carotid artery resection for
patients with head and neck neoplasm].
PMID- 17039816
TI - [Correlated questions of tympanoplasty].
PMID- 17039817
TI - Alternatives to traditional Medicare: Medicare Part C poised to prosper.
AB - Recent events indicate that Medicare Part C (Medicare Advantage) plans are poised
to prosper. Yet many employers express hesitation to offer Medicare Advantage,
formerly known as Medicare+Choice, plans to their retirees because they are
concerned about the potential withdrawal of those plans if there is a reversal of
federal funding rules. This article addresses those concerns. It provides a
historical overview of Medicare Part C and describes the impact of the most
recent agency guidance. The author cites plan trends, raises employer
implications and concludes that Medicare Advantage plans will continue to expand,
possibly facilitated by employers as they implement leading-edge retiree medical
designs.
PMID- 17039818
TI - What comes after the retiree drug subsidy?
AB - Under the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of
2003 and agency guidance that has followed, an employer now faces many options,
such as contracting with a supplemental prescription drug plan, offering its own
prescription drug plan or eliminating its retiree drug subsidy. This article
discusses the complex financial, administrative and communication issues an
employer must ponder. For instance, short-term cash savings must be weighed
against longer term accounting implications; yet the best financial alternative
may come with other baggage that offsets the dollar savings. The author uses data
to show what employers have done to date and raises unresolved issues employers
must address as Medicare Part D evolves.
PMID- 17039819
TI - Beyond the subsidy: Medicare Part D employer options.
AB - The Medicare Modernization Act, now more than a year old, is opening up an array
of possibilities for employers in dealing with retiree medical benefits. Many
employers are beginning to look beyond the question of whether to accept
Medicare's prescription drug subsidy and are more broadly considering how to
shape their retiree health plans. This article describes the options available to
employers now that Medicare Part D is in place. Through this analysis, the
authors also explain how the choices employers make could affect retiree medical
benefits and workforce planning issues.
PMID- 17039820
TI - Evolving with Medicare: an approach to retirement strategy.
AB - With Medicare Part D now providing prescription drug coverage, employers' retiree
health plans are ripe for change. Effective change requires more than just
adjustments. A global or enterprisewide approach to the development of a
retirement strategy is important and should encompass five components: design,
finance, administration, communication and control. This article discusses the
strategic approach to crafting retiree health policy as the Medicare landscape
continues to evolve.
PMID- 17039821
TI - Health plans--eligibility decisions--preemption. DiFelice v. Aetna U.S.
Healthcare.
PMID- 17039822
TI - FMLA-serious health condition. Perry v. Jaguar of Troy.
PMID- 17039823
TI - Child death review teams: a vital component of child protection.
AB - The alarming number of children killed and seriously injured as a result of child
maltreatment and neglect has led to increased calls for action. In response,
interdisciplinary and multiagency child death review teams have emerged as an
important component of child protection. Paradoxically, child death review teams
are among the least visible and understood elements in efforts to protect
children. This article examines the role and functions of child death review
teams and their contributions to child welfare in practice, prevention, and
policy.
PMID- 17039824
TI - Indian Family Exception Doctrine: still losing children despite the Indian Child
Welfare Act.
AB - Since 1982, the Indian Family Exception Doctrine has been circumventing the
Indian Child Welfare Act of 1978. Although not clearly defined, the doctrine has
been pivotal in several American Indian child welfare cases in the United States.
Over time, the doctrine continues to evolve and self-define. Several phrases have
become part of the definition, such as Indian family and culture. This doctrine
presents major concerns and implications in the field of child welfare.
PMID- 17039825
TI - Comprehensive Family Services and customer satisfaction outcomes.
AB - Comprehensive Family Services (CFS) is a strengths-based and partnership-oriented
approach to casework implemented through multiple initiatives. This study
examines the relationship between the practice of CFS and satisfaction of
clients, foster parents, and community partners. CFS indicators are paired with
statewide customer satisfaction survey results. CFS practices are associated with
significantly higher customer satisfaction that improved over time for all
groups. Although causality cannot be determined, the relationship is consistent,
robust, and meaningful.
PMID- 17039826
TI - The impact of state TANF policy decisions on kinship care providers.
AB - Based on a survey of public assistance and child welfare agency staff, this
article examines how state Temporary Assistance for Needy Families (TANF) policy
decisions have affected kinship care providers. Findings indicate that most
states have continued using TANF to provide income support to kinship caregivers,
and some have used TANF to find related support services. These payments,
however, are much lower than rates for licensed providers, and many kinship
caregivers are subject to work, training requirements, and time limits.
PMID- 17039827
TI - The relationship of severe acute respiratory syndrome coronavirus with avian and
other coronaviruses.
AB - In February 2003, a severe acute respiratory syndrome coronavirus (SARS-CoV)
emerged in humans in Guangdong Province, China, and caused an epidemic that had
severe impact on public health, travel, and economic trade. Coronaviruses are
worldwide in distribution, highly infectious, and extremely difficult to control
because they have extensive genetic diversity, a short generation time, and a
high mutation rate. They can cause respiratory, enteric, and in some cases
hepatic and neurological diseases in a wide variety of animals and humans. An
enormous, previously unrecognized reservoir of coronaviruses exists among
animals. Because coronaviruses have been shown, both experimentally and in
nature, to undergo genetic mutations and recombination at a rate similar to that
of influenza viruses, it is not surprising that zoonosis and host switching that
leads to epidemic diseases have occurred among coronaviruses. Analysis of
coronavirus genomic sequence data indicates that SARS-CoV emerged from an animal
reservoir. Scientists examining coronavirus isolates from a variety of animals in
and around Guangdong Province reported that SARS-CoV has similarities with many
different coronaviruses including avian coronaviruses and SARS-CoV-like viruses
from a variety of mammals found in live-animal markets. Although a SARS-like
coronavirus isolated from a bat is thought to be the progenitor of SARS-CoV, a
lack of genomic sequences for the animal coronaviruses has prevented elucidation
of the true origin of SARS-CoV. Sequence analysis of SARS-CoV shows that the 5'
polymerase gene has a mammalian ancestry; whereas the 3' end structural genes
(excluding the spike glycoprotein) have an avian origin. Spike glycoprotein, the
host cell attachment viral surface protein, was shown to be a mosaic of feline
coronavirus and avian coronavirus sequences resulting from a recombination event.
Based on phylogenetic analysis designed to elucidate evolutionary links among
viruses, SARS-CoV is believed to have branched from the modern Group 2
coronaviruses, suggesting that it evolved relatively rapidly. This is significant
because SARS-CoV is likely still circulating in an animal reservoir (or
reservoirs) and has the potential to quickly emerge and cause a new epidemic.
PMID- 17039828
TI - Increased level of Eimeria sensitivity to diclazuril after using a live coccidial
vaccine.
AB - Anticoccidial vaccine and an anticoccidial drug rotation program were compared to
determine which program was more effective in producing coccidia populations
sensitive of 1 ppm diclazuril. The study used an anticoccidial drug-sensitivity
battery test (AST) to determine the baseline level of diclazuril sensitivity to
field isolates of Eimeria spp. from seven broiler complexes that had used
diclazuril. Based on percentage reduction in weight gain and lesion scores, 25%
or fewer of the isolates were effectively controlled by diclazuril. Following the
baseline sampling, four of the complexes switched to a nondiclazuril in-feed
anticoccidial drug program and three of the complexes switched to a vaccination
program for two broiler grow-out cycles as the sole coccidiosis-control program.
This study demonstrated that the vaccine used (Coccivac-B) contained
anticoccidial drug-sensitive strains. Eimeria isolates were subsequently
collected from the identical houses and diclazuril AST results were compared with
the baseline AST results. Following the two grow-out cycles, sensitivity of the
isolates to diclazuril from the four complexes that continued to use in-feed
anticoccidial drugs remained essentially unchanged. The isolates from the three
complexes that switched to the vaccination program demonstrated a marked increase
in diclazuril sensitivity, with 60%-100% of the isolates from each complex
effectively controlled by diclazuril. Vaccination with the anticoccidial drug
sensitive strains produced a measurable increase in the level of sensitivity to
diclazuril.
PMID- 17039829
TI - Development and evaluation of a DAS-ELISA for rapid detection of avian influenza
viruses.
AB - Rapid detection of avian influenza virus (AIV) infection is critical for control
of avian influenza (AI) and for reducing the risk of pandemic human influenza. A
double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was
developed for this purpose. The method employed a monoclonal antibody (MAb) as
the capture antibody and rabbit polyclonal IgG labeled with horseradish
peroxidase as the detector antibody, and both antibodies were against type
specific influenza A nucleoprotein (NP). The DAS-ELISA could detect minimally 2.5
ng of influenza viral protein in virus preparations treated with Triton X-100,
which is equvilent to 2.5 x 10(2) EID50 virus particles. This DAS-ELISA could
detect all 15n AIV subtypes (H1-H15) and did not cross react with other avian
pathogens tested. The DAS-ELISA were directly compared with virus isolation (VI)
in embryonated chicken eggs, the current standard of influenza virus detection,
for 805 chicken samples. The DAS-ELISA results correlated with VI results for
98.6% of these samples, indicating a sensitivity of 97.4% and specificity of
100%. The method was further tested with H5N1 and H9N2 AIV experimentally
infected chickens, ducks, and pigeons, as well as field samples obtained from
central China in 2005. The DAS-ELISA method has demonstrated application
potential as an AIV screening tool and as a supplement for virus isolation in
Asia.
PMID- 17039830
TI - Characterization of monoclonal antibodies against fowl adenovirus serotype 1
(FAV1) isolated from gizzard erosion.
AB - Six clones of monoclonal antibodies (Mabs) to fowl adenovirus (FAV) serotype 1
were produced. All Mabs reacted positively by enzyme-linked immunosorbent assay.
Three Mabs recognized the putative 100-kD hexon protein and reacted to serotype 1
specifically by western blot analysis but did not react to other FAV serotypes
(2, 3, 4, 5, 6, 7, and 8a). These Mabs will be useful for immunodiagnosis of FAV
serotype 1 infection in chickens with gizzard erosion and in further research
studies involving the genomes and proteins of FAV serotype 1.
PMID- 17039831
TI - Susceptibility and protection of naive and vaccinated racing pigeons (Columbia
livia) against exotic Newcastle disease virus from the California 2002-2003
outbreak.
AB - The susceptibility, immune response, and protection to challenge after
vaccination in racing pigeons (Columbia livia) was assessed with the 2002-2003
exotic Newcastle disease (END) virus responsible for the most recent major
outbreak in Southern California. Immunologically naive pigeons appeared resistant
to disease, regardless of dose, after a natural route of exposure. Twenty percent
morbidity was observed in each group of birds receiving between 10(2.1) and
10(8.1) 50% embryo infectious dose (EID50) per bird, with one bird succumbing to
challenge in the 10(8.1) EID50/bird group at day 12 postinoculation. Although
resistant to disease, birds in all groups continued to shed virus from either
oral or cloacal route at the end of the 14-day sampling period, and
seroconversion was only observed in birds receiving > or =10(6.1) EID50. Single
or double vaccination of juvenile and adult birds with pigeon paramyxovirus virus
type 1 (PPMV-1) vaccine followed by END challenge with 10(6.1) EID50/bird
decreased the duration, incidence, and viral load. A positive correlation was
observed between the presence of hemagglutination-inhibiting antibody titers at
challenge and decreased viral shedding. Overt clinical signs of disease were not
observed in any PPMV-1-vaccinated birds after challenge.
PMID- 17039832
TI - Susceptibility of various parental lines of commercial white leghorn layers to
infection with a naturally occurring recombinant avian leukosis virus containing
subgroup B envelope and subgroup J long terminal repeat.
AB - Chickens from seven different parental lines of commercial White Leghorn layer
flocks from three independent breeders were inoculated with a naturally occurring
avian leukosis virus (ALV) containing an ALV-B envelope and an ALV-J long
terminal repeat (LTR) termed ALV-B/J. Additional groups of chickens from the same
seven parental lines were inoculated with ALV-B. Chickens were tested for ALV
viremia and antibody at 0, 4, 8, 16, and 32 wk postinfection. Chickens from all
parental lines studied were susceptible to infection with ALV-B with 40%-100% of
inoculated chickens positive for ALV at hatch following embryo infection.
Similarly, infection of egg layer flocks with the ALV-B/J recombinant virus at 8
days of embryonation induced tolerance to ALV with 86%-100% of the chickens
viremic, 40%-75% of the chickens shedding virus, and only 2/125 (2%) of the
chickens producing serum-neutralizing antibodies against homologous ALV-B/J
recombinant virus at 32 wk postinfection. In contrast, when infected with the ALV
B/J recombinant virus at hatch, 33%-82% of the chickens were viremic, 28%-47%
shed virus, and 0%-56% produced serum-neutralizing antibodies against homologous
ALV-B/J recombinant virus at 32 wk postinfection. Infection with the ALV-B/J
recombinant virus at embryonation and at hatch induced predominately lymphoid
leukosis (LL), along with other common ALV neoplasms, including erythroblastosis,
osteopetrosis, nephroblastomas, and rhabdosarcomas. No incidence of myeloid
leukosis (ML) was observed in any of the commercial White Leghorn egg layer
flocks infected with ALV-B/J in the present study. Data suggest that the parental
line of commercial layers may influence development of ALV-B/J-induced viremia
and antibody, but not tumor type. Differences in type of tumors noted in the
present study and those noted in the field case where the ALV-B/J was first
isolated may be attributed to differences in the genetics of the commercial layer
flock in which ML was first diagnosed and the present commercial layer flocks
tested in the present study.
PMID- 17039833
TI - Detection and sequence analysis of avian polyomavirus and psittacine beak and
feather disease virus from psittacine birds in Taiwan.
AB - Avian polyomavirus (APV) and psittacine beak and feather disease virus (PBFDV)
are the most common viral diseases of psittacine birds. In Taiwan, however, the
existence of these viruses in psittacine birds has not been established.
Polymerase chain reaction (PCR) methodology was therefore employed to ascertain
whether APV and PBFDV genomes were present in isolates from psittacine birds of
Taiwan. A total of 165 psittacine birds belonging to 22 genera were examined
between 2002 and 2005. Findings revealed an APV-positive rate of 15.2%, a PBFDV
positive rate of 41.2%, and an APV/PBFDV dual infection rate of 10.3%. After
cloning and sequencing, sequences of the PCR products were compared with
sequences obtained from GenBank. For APV, the nucleotide identity among VP1 and
t/T antigen coding regions ranged from 97.5% to 100% and 97.6% to 100%,
respectively. For PBFDV, the nucleotide identity of ORF V1 and ORF C1 sequences
ranged from 92.2% to 100% and 83.3% to 100%, respectively. The derived amino acid
sequence alignment for PBFDV ORF V1 fragments revealed the conservation of two
replication motifs and of the nucleotide binding site motif. In PBFDV, six of 42
deduced positions in the ORF C1 amino acid sequence were considered
hypervariable. The established phylogenetic trees based on the four genome
fragments examined in this study did not allow the assignment of particular APV
or PBFDV nucleotide sequences to distinct avian species.
PMID- 17039834
TI - Susceptibility of adult chickens, with and without prior vaccination, to
challenge with Marek's disease virus.
AB - Marek's disease (MD) outbreaks can occur in previously healthy adult layer or
breeder flocks. However, it is not clear whether such outbreaks are caused by
recent challenge with highly virulent (vv and vv+) strains of MD virus (MDV; i.
e., new infection hypothesis) or by exacerbation of an earlier MDV infection (i.
e., old infection hypothesis). To discriminate between these hypotheses, adult
White Leghorn chickens of laboratory strains or commercial crosses with or
without prior vaccination or MDV exposure were challenged at 18-102 wk of age
with highly virulent MDVs, and lesion responses were measured. Horizontal
transmission was studied in one trial. Challenge of adult chickens, which were
free from prior MDV vaccination or exposure, with highly virulent MDV strains
induced transient paralysis or tumors in 60%-100% of 29 groups (mean = 91%), and
horizontal spread of virus was detected. The magnitude of the response was
similar to that induced by challenge at 3 wk of age. In contrast, comparable
challenge of adult chickens, which had been vaccinated or exposed to MDV early in
life, induced transient paralysis or tumors in 0%-6% of 12 groups (mean = 0. 5%),
although some birds showed limited virologic evidence of infection and
transmission of the virus to contacts. The MD responses were influenced by the
virulence of the challenge virus strain, and to a lesser extent by virus dose and
route of exposure. Strong inflammatory lesions were induced in the brain and
nerves of adult specific pathogen-free (SPF) chickens at 9-15 days after
infection. The low susceptibility of previously vaccinated and exposed groups to
challenge at > or =18 wk of age suggests that late outbreaks of MD in commercial
flocks are not likely a result of recent challenge alone and that additional
factors could be involved.
PMID- 17039835
TI - Effects of nonimmunized egg yolk powder-supplemented feed on Salmonella
enteritidis prevention and elimination in broilers.
AB - Chicken consumption is a newly identified risk factor in Salmonella enterica
serovar Enteritidis (SE) infection in humans. SE is widely distributed in
commercial chicken flocks and high levels of cecal carriage and shedding may lead
to broiler meat contamination. In the present study, the preventive and
eliminative effect of nonimmunized freeze-dried egg yolk powder (EYP) on SE in
broilers was investigated. In the prevention trial, reduced SE counts were
observed in liver (P < or = 0.05), cecal contents, and fecal shedding (P < or =
0.05) in birds fed 10% or 5% EYP. Histological examination of cecal wall and
cecal tonsils at 23 days postinfection indicated a lesser degree of intestinal
pathology. In the elimination trial, a significantly lower (P < or = 0.05) number
of SE reached the liver and spleen, and a reduction in cecal carriage and fecal
shedding was observed. The histological changes in the cecal mucosa and cecal
tonsils reflected an apparent inflammation and mucosal repair and also suggested
that the infection had not completely resolved, confirming SE bacterial
isolations in the cecal tissue. The present study indicates that supplementing
the diets of broilers with 5% nonimmunized EYP, at the early stages of the
growing period, reduces preharvest Salmonella load with a minimal degree of
intestinal pathology.
PMID- 17039836
TI - Persistence of immunity in commercial egg-laying hens following vaccination with
a killed H6N2 avian influenza vaccine.
AB - The California poultry industry experienced an outbreak of H6N2 avian influenza
beginning in February 2000. The initial infections were detected in three
commercial egg-laying flocks and a single noncommercial backyard flock but later
spread to new premises. The vaccination of pullet flocks with a commercially
prepared, killed autogenous vaccine prior to their placements on farms with
infected or previously infected flocks was used as a part of the eradication
programs for some multiage, commercial egg production farms. The purpose of this
study was to follow three vaccinated flocks on two commercial farms to track the
immune responses to vaccination. The antibody-mediated responses of the three
flocks followed in this study were markedly different. One flock achieved 100%
seroconversion at 12.5 wk of age, but by 32 wk of age, all of the hens were
seronegative by agar gel immunodiffusion (AGID). In contrast, at 32 wk of age,
flocks from the other farm (flocks 2A and 2B) were 95% and 72% seropositive by
AGID, respectively. Of the differences that were identified between the
vaccination protocols on the two farms, the distinction that could explain the
level of disparity between responses is the delivery of the second dose of
vaccine with a bacterin on the first farm, which may have interfered with the
persistence of immunity in this flock. Hens from flocks 2A and 2B were
experimentally challenged at 25 wk of age with H6N2 avian influenza virus. Hens
from flock 2A did not transmit virus to naive contact-exposed hens, but hens from
flock 2B did. At 34 wk of age, hens from flock 2A were again challenged and naive
contact-exposed hens were infected in this second trial. These challenge
experiments served to demonstrate that despite detectable antibody responses in
flocks 2A and 2B, the birds were protected from infection for less than 21 wk
after the second vaccination.
PMID- 17039837
TI - Isolation and characterization of an adventitious avian leukosis virus isolated
from commercial Marek's disease vaccines.
AB - Commercial Marek's disease (MD) vaccines produced by two manufacturers were
tested for possible contamination with avian leukosis virus (ALV). Samples of MD
vaccines manufactured by two companies (A and B) were received from a breeder
company; samples were also received directly from vaccine company B. Using virus
isolation tests, samples initially tested positive for subgroup E (endogenous)
ALV. However, upon repassage, the vaccines also tested positive for exogenous
ALV. The isolated exogenous ALV proved to be a subgroup A virus, as determined by
flow cytometry using polyclonal chicken antibodies specific for various subgroups
of ALV, and by DNA sequencing of the envelope glygoprotein (gp85). The exogenous
ALV isolated from MD vaccines was inoculated in chickens from ADOL lines 15I(5) x
7(1) and 0 to determine its pathogenicity and compare it with that of Rous
associated-virus-1 (RAV-1), the prototype strain of ALV-A. Each chicken from each
line was inoculated with approximately 10,000 infectious units of RAV-1 or the
ALV-A isolated from vaccines termed B-39 virus at 7th day of embryonation. At
hatch, and at 4, 8, and 16 wk of age, chickens were tested for viremia and
cloacal shedding; chickens were also observed for ALV-induced tumors within 16 wk
of age. Viremia and cloacal shedding results suggest that chickens from both
lines were susceptible to infection with either virus. Within 16 wk of age, the
proportion of ALV tumors induced by strain B-39 in line 0 and line 15I5 x 7(1)
chickens was 0% and 12%, respectively, compared with 62% and 67% in chickens
inoculated with RAV-1. The data indicate that commercial MD vaccines produced by
two manufacturers were contaminated with endogenous subgroup E and an exogenous
subgroup A ALV. Further, data from biological characterization suggest that the
ALV-A isolated from commercial MD vaccines is of low oncogenicity, compared with
that of RAV-1. GenBank accession numbers: The gp85 gene sequences of ALV isolated
from commercial Marek's disease vaccines have been deposited in GenBank and
assigned the following accession numbers: A46 subgroup A, DQ412726 ; B53 subgroup
A, DQ412727; A46 subgroup E, DQ412728; B53 subgroup E, DQ412729.
PMID- 17039838
TI - Isolation, identification, and comparison of four isolates of avian paramyxovirus
serotype 2 in China.
AB - Four Yucaipa-like viruses of avian paramyxovirus serotype 2 (APMV-2) were
isolated in China from the imported Gouldian Finch (Chloebia gouldiae) and
broilers in 1998-2002, and were named F4, F6, F8, and NK, respectively. Examined
under electron microscope, the isolates were found to be round in shape and
varying in size. The results of the hemagglutination inhibition test and indirect
enzyme-linked immunosorbent assay (using monoclonal antibodies) showed some
differences between the isolates and the reference strain Yucaipa. The isolates
derived from chickens had a closer relationship to Yucaipa virus than did those
of finches. Sequence comparison of the fusion gene and the haemagglutinin
neuraminidase gene showed similar results, although the variations were lesser
among APMV-2 viruses in nucleotide and amino acid sequence. By sequence
comparison, it was also revealed that at the molecular level the four virus
strains belong to APMV-2, and that two of the strains were isolated from the same
group of imported Gouldian Finches.
PMID- 17039839
TI - Molecular analysis of infectious bursal disease virus from bursal tissues
collected on FTA filter paper.
AB - We investigated the feasibility of using FTA filter cards for the storage of
bursas of Fabricius containing infectious bursal disease virus (IBDV) and for
IBDV detection by reverse transcriptase (RT)-polymerase chain reaction (PCR), and
characterization by restriction fragment length polymorphism (RFLP) or nucleotide
sequencing. The FTA card is a cotton-based cellulose membrane containing
lyophilized chemicals that lyses many types of bacteria and viruses. IBDV was
inactivated upon contact with the FTA as shown by the inability of the virus to
be propagated in embryonating chicken eggs. Viral RNA in minced bursas or stamped
bursas could be amplified by RT-PCR (VP2 gene fragment, 248 base pairs) after
storage on FTA for at least 15 days at room temperature or 8 mo at -20 C.
Analytical sensitivity of the test was between 0.5-5 ng of RNA template or 5 x
10(1) mean tissue culture infective dose (TCID50)/FTA spot. Detection rate of
IBDV in domestic clinical samples collected on FTA or collected by the non-FTA
standard procedure was 36.7% and 41.7%, respectively, which represents 88%
agreement. Detection of IBDV from FTA cards inoculated with bursal tissues in the
laboratory or in the field was 36.7% and 37.1%, respectively. Detection of IBDV
from FTA samples when the cards were inoculated with bursal tissues and sent
through customs into the United States was 32.9%. Analysis of the amplified
products showed that molecular characterization of IBDV by RFLP or nucleotide
sequencing is feasible in bursas stored on FTA at 25 C for 1-3 mo or at -20 C for
at least 8 mo. The use of FTA for the collection of bursal tissues and
simultaneous inactivation of IBDV allows the movement of specimens within the
United States and also from outside the United States in compliance with federal
regulations and in a manner adequate for molecular characterization.
PMID- 17039840
TI - Molecular characterization and typing of chicken and turkey astroviruses
circulating in the United States: implications for diagnostics.
AB - Avian astroviruses were detected by reverse transcriptase and polymerase chain
reaction in intestinal contents collected from commercial chickens and turkeys
from throughout the United States from 2003 through 2005. Astroviruses were
detected in birds from both healthy and poorly performing flocks with or without
enteric disease. Phylogenetic analysis was performed with sequence data from the
polymerase (ORF-1b) genes of 41 turkey-origin astroviruses and 23 chicken-origin
astroviruses. All currently available avian astrovirus sequence data and selected
mammalian astrovirus sequence data were included in the analysis. Four groups of
avian astroviruses were observed by phylogenetic analysis: turkey astrovirus type
1 (TAstV-1)-like viruses, turkey astrovirus type 2 (TAstV-2)-like viruses, both
detected in turkeys; avian nephritis virus (ANV)-like viruses, detected in both
chickens and turkeys; and a novel group of chicken-origin astroviruses (CAstV).
Among these four groups, amino acid identity was between 50.1% and 73.8%, and was
a maximum of 49.4% for all avian isolates when compared with the mammalian
astroviruses. There were multiple phylogenetic subgroups within the TAstV-2, ANV,
and CAstV groups based on 9% nucleotide sequence divergence. Phylogenetic
analysis revealed no clear assortment by geographic region or isolation date.
Furthermore, no correlation was observed between the detection of a particular
astrovirus and the presence of enteric disease or poor performance. Based on
these data, a revision of the present taxonomic classification for avian
astroviruses within the genus Avastrovirus is warranted.
PMID- 17039841
TI - Occurrence of pathogenicity island I(APEC-O1) genes among Escherichia coli
implicated in avian colibacillosis.
AB - Colibacillosis caused by avian pathogenic Escherichia coli (APEC) is a leading
cause of economic loss to the poultry industry worldwide. The ability of APEC to
cause disease is determined by certain virulence markers, some of which are
located on pathogenicity islands (PAls). We recently described one such PAI in an
APEC O1:K1 strain (APEC-O1). This PAI, termed PAI I(APEC-O1), carries the genes
of the pap operon, a region similar to the tia invasion determinant of
enterotoxigenic E coli; ireA, a gene that encodes an iron-responsive element; and
a novel 1.5-kb region, ORF 54. Here, the occurrence of six selected loci of PAI
I(APEC-O1) (papA, papC, papG, ireA, tia, and ORF 54) among APEC and fecal E. coli
strains from apparently healthy chickens (avian commensal E. coli) was determined
using polymerase chain reaction (PCR) techniques. None of the commensal E. coli
was positive for all six traits, whereas 7.2% of the APEC isolates were positive
for all the traits. Although there was no significant difference in the
occurrence of ORF 54 among APEC and commensal E. coli, tia, ireA, papC, and papG
genes were predominantly present in APEC rather than in avian commensal E. coli.
papA was detected in only 6.3% of APEC, perhaps because of the presence of
allelic variants of the gene. Additionally, the presence of all six traits was
tested with PCR in APEC isolates collected in the 1980s, and these results were
compared with those obtained with the APEC isolated in the 1990s. There was no
significant difference in the occurrence of tia, ireA, papC, papG, and ORF 54
between APEC isolates collected during the different decades. However, papA was
more frequently present in APEC from the 1980s than it was in APEC from the
1990s. Phylogenetic group of an isolate did not correlate with pathogenicity or
the presence of PAI traits, except that more APEC of the low-pathogenicity group
belonged to the phylogenetic group B1. However, PAI traits occurred more
frequently in isolates belonging to the intermediate- and high-pathogenicity
groups than in isolates of low pathogenicity.
PMID- 17039842
TI - Detection of rotaviruses and intestinal lesions in broiler chicks from flocks
with runting and stunting syndrome (RSS).
AB - The intestinal tract and intestinal contents were collected from 34 stunted, 5-to
14-day-old broiler chicks from eight flocks with runting and stunting syndrome
(RSS) in Northern Germany to investigate intestinal lesions and the presence of
enteric pathogens with a special focus on rotaviruses (RVs). Seven chicks from a
healthy flock were used as controls. Severe villous atrophy was seen in chicks
from six flocks with RSS but not in the control flock. Lesions were often
"regionally" distributed in the middle-to-distal small intestine. Transmission
electron microscopy (TEM), polyacrylamide-gel electrophoresis (PAGE), reverse
transcriptase polymerase chain reaction (RT-PCR), and seminested RT-PCR were used
for detection and characterization of RVs. The PAGE allows discrimination of
different RV groups, and the RT-PCR was used to verify the presence of group (gp)
A RVs. RVs were detected (by all methods) in 32 of 34 chicks from the flocks with
RSS. By TEM (negative staining), RV particles were observed in intestinal
contents of 28 chicks from the flocks with RSS. PAGE analysis showed four RV
groups: gpA, gpD, gpF, and gpG. Group A RVs were detected in four chicks from two
flocks with RSS, without intestinal lesions. GpD RVs were detected in 12 chicks
of five flocks with RSS, 10 of them with severe villous atrophy. GpF RVs were
confirmed in four chicks from three flocks with RSS and in two birds in the
control flock. GpG RVs were verified in two chicks from two flocks with RSS, one
with, and one without, intestinal lesions. At present, PCR methods are only
available for detection of gpA RVs. Using RT-PCR, gpA RVs were identified in
samples from 22 chicks including samples of two chicks from the control flock.
Statistical analysis revealed a positive correlation between presence of gpD RV
and severe villous atrophy in flocks with RSS. The results suggest that gpD RV
plays a major role in the pathogenesis of RSS.
PMID- 17039843
TI - Production and characterization of monoclonal antibodies that react to the
nucleocapsid protein of avian metapneumovirus subtype C.
AB - Monoclonal antibodies (MAbs) were prepared against avian metapneumovirus (aMPV)
subtype C (aMPV/ Minnesota/turkey/1a/97). Six MAbs were selected based on enzyme
linked immunosorbent assay activities and characterized by isotyping,
neutralization test, western blot analysis, and immunohistochemistry assay. The
results showed that three MAbs (3E, 9D, and 12C) belonged to the IgG1 subclass,
whereas the other three (5D, 8E, and 16E) were of the IgG2a subclass. None of the
six MAbs neutralized aMPV infectivity at a detectable level, but all reacted with
both denatured and nondenatured forms of the nucleocapsid (N) protein of aMPV,
suggesting that these MAbs may recognize structurally independent epitopes of the
N protein. These MAbs provide new tools and methods for investigating aMPV
infection and pathogenesis, as well as diagnosis of aMPV disease.
PMID- 17039844
TI - Comparison of Salmonella enterica serovar enteritidis levels in crops of fed or
fasted infected hens.
AB - Long-term feed withdrawal has been shown to increase ileocecal intestinal
colonization and fecal shedding of Salmonella enterica serovar Enteritidis in
challenged hens. Less information is available regarding effects of fasting on
crop colonization. Two trials were conducted to compare effects of 14-day feed
withdrawal vs. full feed on crop colonization in hens challenged with Salmonella
Enteritidis. The levels of Salmonella Enteritidis in the crops of fasted hens
were significantly higher than in nonfasted hens on days 3 and 10 and days 3, 9,
and 16 postinfection (PI) in trials 1 and 2, respectively. Fecal shedding of
Salmonella Enteritidis was significantly increased in the fasted hens on day 10
PI in trial 1. Analysis of crop IgA anti-Salmonella Enteritidis
lipopolysaccharide levels in crop lavage samples of hens in trial 1 revealed a
humoral response PI in both treatment groups with no significant differences,
although peak response for fasted hens occurred 1 wk later. Histologic evaluation
of hematoxylin and eosin-stained crop sections from trial 1 birds revealed mild
to moderate heterophilic infiltration within the crop lamina propria (LP) or LP
and epithelium of nonfasted infected hens at 24 and 96 hr PI. In comparison,
heterophils in crops of fasted hens infected at this time point were sparse,
indicating a possible diminished heterophil response in the fasted birds.
Multifocal areas of tissue inflammation, as indicated by marked heterophil
infiltration, with necrosis and sloughing of epithelium, were observed in crops
from fasted hens at day 11 PI (14th day of feed withdrawal) but not in the fed
groups. This severe heterophilic inflammation was observed in both challenged and
nonchallenged fasted hens, suggesting that some factor other than Salmonella
Enteritidis was responsible. These results indicate that feed withdrawal can have
a dramatic effect on the integrity of the crop and its ultimate response to
infection.
PMID- 17039845
TI - Presence of inoculated Campylobacter and Salmonella in unabsorbed yolks of male
breeders raised as broilers.
AB - Day-old male broiler breeder chicks were obtained from a commercial hatchery and
raised as broilers. For Experiment 1, at 5 wk of age, the broilers were orally
inoculated with a 10(6) cfu/ml of a characterized strain of Campylobacter jejuni
and a cocktail (three naladixic acid-resistant strains) of Salmonella serovars.
One week after inoculation, the birds were euthanatized and defeathered. The
abdominal cavity was examined and any unabsorbed yolk material (and remaining
yolk stalk) and ceca were aseptically removed for microbiological analyses. For
each pooled sample (two birds per pool), an aerobic plate count (APC), an
Enterobacteriaceae (ENT) count, and a test for the presence of Campylobacter and
Salmonella was performed. For Experiment 2, at 5 wk of age, the broilers were
orally inoculated with 10(5) cfu/ml of a characterized strain of Campylobacter
jejuni. One week after inoculation, the birds (n = 20) were killed, defeathered,
and the yolk stalk, attached yolk, or free-floating yolk and ceca were
individually analyzed for presence of Campylobacter. For Experiment 1, the
Salmonella-inoculated birds had 2/12 ceca and 0/12 unabsorbed yolk samples
positive for Salmonella. The average yolk APC was log10 3.4 cfu/g and the average
ENT was log10 1.9 cfu/g. For the Campylobacter-inoculated birds, 12/12 ceca and
9/12 unabsorbed yolk samples were positive for Campylobacter. The average yolk
APC was log10 3.5 cfu/g and the average ENT was log10 3.1 cfu/g. For Experiment
2, the inoculated Campylobacter birds had 19/20 ceca, 5/20 free floating yolks,
and 19/20 yolk stalks positive. In Experiment 1, the inoculated Campylobacter
colonized the ceca in every instance and were present in 75% of the unabsorbed
yolks. Alternatively, the inoculated Salmonella were not found in any of the
unabsorbed yolks and only rarely in the ceca. In Experiment 2, the inoculated
Campylobacter was found in very high numbers in the yolk and internal body
samples. Determining to what extent these internal bodies and unabsorbed yolks
play in bacterial colonization and contamination of the birds at processing has
not been determined. The next step will be to determine the incidence of
unabsorbed yolks and presence of Campylobacter and Salmonella in these bodies of
commercial broilers at processing.
PMID- 17039846
TI - Higher incidence of Eimeria spp. field isolates sensitive for diclazuril and
monensin associated with the use of live coccidiosis vaccination with paracox-5
in broiler farms.
AB - Twenty European Eimeria spp. field isolates were subjected to an anticoccidial
sensitivity test (AST). The anticoccidial drugs tested were diclazuril (Clinacox)
and monensin (Elancoban). The assay was performed in a battery cage trial.
Infected medicated birds were compared with an unmedicated control group.
Coccidial lesion scores and oocyst shedding were used as parameters. The results
of the AST show that resistance is common amongst coccidiosis field isolates,
especially Eimeria acervulina (68% and 53% resistance for diclazuril and
monensin, respectively). Resistance is less frequent amongst Eimeria maxima (38%
and 50% resistance for diclazuril and monensin, respectively) and Eimeria tenella
isolates (23% and 38% resistance for diclazuril and monensin, respectively). A
highly significant influence of the coccidiosis prevention program (live
coccidiosis vaccination with Paracox-5 vs. anticoccidial drugs in feed) on the
sensitivity patterns of Eimeria spp. field isolates for both diclazuril (P=
0.000) and monensin (P= 0.001) was found. Further, when looking at the single
species and each anticoccidial drug level, significantly more sensitivity of E.
acervulina for monensin (P= 0.018), E. maxima for diclazuril (P = 0.009), and E.
tenella for diclazuril (P = 0.007) was found in isolates originating from
vaccinated flocks. Moreover, for E. acervulina and diclazuril, E. maxima and
monensin, and E. tenella and monensin a trend toward higher sensitivity of
isolates for these products was found when live coccidiosis vaccination was
applied. The present study shows that sensitivity for the anticoccidial drugs
diclazuril and monensin is more frequent in Eimeria spp. field isolates
originating from broiler farms where a coccidiosis vaccination policy is
followed.
PMID- 17039847
TI - Isolation and molecular biological investigations of avian poxviruses from
chickens, a turkey, and a pigeon in Croatia.
AB - In the last 3 yr, several outbreaks of avian poxviruses (APVs) have been observed
in different parts of Croatia. Four strains of APVs, from chickens, a pigeon, and
a turkey, were isolated from cutaneous lesions by inoculation onto the
chorioallantoic membranes (CAM) of 12-day-old specific-pathogen-free chicken
embryos. The resulting proliferative CAM lesions contained eosinophilic
cytoplasmic inclusion bodies. The characteristic viral particles of poxvirus were
detected in the infected CAM and also in the infected tissues by transmission
electron microscopy. Further identification and differentiation of the four
various APVs were carried out by the use of a polymerase chain reaction (PCR)
combined with restriction enzyme analysis. Using one primer set, which framed a
region within the APV 4b core protein gene, it was possible to detect APV
specific DNA from all four tested isolates. PCR results revealed no recognizable
differences in size of amplified fragments between the different APVs from
chickens, turkey, and pigeon. Restriction enzyme analysis of PCR products using
NlaIII showed the same cleavage pattern for turkey and chicken isolates and a
different one for the pigeon isolate. Multiplex PCR for direct detection of APV
and reticuloendotheliosis virus (REV) was carried out to determine the possible
integration of REV in the genome of isolated APVs. The obtained results revealed
that REV was present in chicken and turkey strains of poxviruses, whereas the
pigeon isolate was negative. It is not known whether the avipoxvirus vaccine
strain used in Croatia is contaminated with REV or if the REV is naturally
contaminating Croatian field strains of fowl poxvirus. The latter is indicated by
the negative REV finding in the pigeon, which was not vaccinated. The results of
the present study indicate the reemergence of fowlpox in Croatia, where
infections have not been recorded since 1963 and never confirmed etiologically.
PMID- 17039848
TI - Characterization of monoclonal antibodies to avian Escherichia coli Iss.
AB - Colibacillosis accounts for annual multimillion dollar losses in the poultry
industry, and control of this disease is hampered by limited understanding of the
virulence mechanisms used by avian pathogenic Escherichia coli (APEC). Previous
work in our laboratory has found that the presence of the increased serum
survival gene (iss) is strongly associated with APEC but not commensal E. coli,
making iss and the protein it encodes (Iss) candidate targets of colibacillosis
control procedures. Previously, we produced monoclonal antibodies (MAbs) against
Iss to be used as a reagent in studies of APEC virulence and colibacillosis
pathogenesis. Unfortunately, the utility of these MAbs was limited because these
MAbs exhibited nonspecific binding. It was thought that the lack of specificity
might be related to the fact that these MAbs were of the immunoglobulin M (IgM)
isotype. In the present study, new MAbs were produced using a different
immunization strategy in an effort to generate MAbs of a different isotype. Also,
because Iss bears strong similarity to Bor, a lambda-derived protein that occurs
commonly among E. coli, MAbs were assessed for their ability to distinguish Iss
and Bor. For these studies, the bor gene from an APEC isolate was cloned into an
expression vector. The fusion protein expressed from this construct was used to
assess the potential of the anti-Iss MAbs produced in the past and present
studies to distinguish Bor and Iss. The MAbs produced in this study were of the
IgG1 isotype, which appeared to bind more specifically to Iss than previously
generated antibodies in certain immunologic procedures. These results suggested
that the MAbs generated in this study might prove superior to the previous MAbs
as a reagent for study of APEC. However, both MAbs recognized recombinant Iss and
Bor, suggesting that any results obtained using anti-Iss MAbs would need to be
interpreted with this cross-reactivity in mind.
PMID- 17039849
TI - Natural presence of Campylobacter spp. in various internal organs of commercial
broiler breeder hens.
AB - Campylobacter are known to cause acute bacterial gastroenteritis in humans.
Poultry products have been implicated as a significant source of these
infections. Six experiments were performed to determine whether Campylobacter
could be isolated naturally from the primary and secondary lymphoid organs,
liver/gallbladder, and ceca of commercial broiler breeder hens. Broiler breeder
hens were acquired from different commercial sources during the early, middle,
and late lay cycles. The birds were euthanatized, defeathered, and aseptically
opened. To reduce the possibility of cross-contamination between samples, the
thymus, spleen, and liver/gallbladder were aseptically removed prior to removal
of the ceca. Individual samples were placed in sterile bags, packed on ice, and
transported to the laboratory for evaluation. In this study Campylobacter were
found in 11 of 43 thymii, eight of 43 spleens, four of 43 liver/gallbladders, and
30 of 43 ceca. Overall, 28 of 53 isolates from the above samples were
Campylobacter coli and 25 of 53 isolates were found to be Campylobacter jejuni.
PMID- 17039850
TI - Passive West Nile virus antibody transfer from maternal Eastern screech-owls
(Megascops asio) to progeny.
AB - Transovarial antibody transfer in owls has not been demonstrated for West Nile
virus (WNV). We sampled chicks from captive adult WNV-antibody-positive Eastern
Screech-Owls (Megascops asio) to evaluate the prevalence of transovarial maternal
antibody transfer, as well as titers and duration of maternal antibodies. Twenty
four owlets aged 1 to 27 days old circulated detectable antibodies with
neutralizing antibody titers ranging from 20 to 1600 (median 1:40). Demonstrating
that WNV antibodies are passively transferred transovarially is important for
accurate interpretation of serologic data from young birds.
PMID- 17039851
TI - West Nile virus-associated mortality events in domestic Chukar partridges
(Alectoris chukar) and domestic Impeyan pheasants (Lophophorus impeyanus).
AB - West Nile virus (WNV) infection was diagnosed in captive juvenile chukars
(Alectoris chukar), and captive juvenile Impeyan pheasants (Lophophorus
impeyanus) on the basis of necropsy, histopathology, polymerase chain reaction,
and immunohistochemistry. The chukars were kept in a game bird farm that
experienced two outbreaks with approximately 25% mortality in hundreds of chukars
between September and October 2002 and during the same months in 2003. The
submitted pheasants were part of a group of 15 juvenile Impeyan pheasants that
all died within approximately 2 wk at the end of August 2002. The macroscopic
lesions in the pheasants were dominated by mucosal hemorrhage at the
proventricular to ventricular junction and cecal ulcers, whereas the gross
lesions in the chukar partridges were nonspecific. The predominant microscopic
lesion in the chukar partridges was myocardial necrosis, whereas fibrinous and
necrotizing splenitis was prominent in the pheasants. Viral antigen was usually
widespread in animals of both species. Spontaneously occurring WNV infection
should be considered a differential diagnosis in cases of mortality among select
species of galliform birds.
PMID- 17039852
TI - Litter impaction of the lower intestinal tract in male broiler breeders.
AB - Increased mortality occurred among males in a house of 26-wk-old broiler
breeders. A severe impaction of the lower intestinal tract, because of litter,
was found on necropsy in two of three recently dead cockerels. Litter could be
seen in the markedly distended vent of the most affected bird. This bird also had
feces and litter in the body cavity because of a ruptured small intestine. Both
birds had extensive urate and fecal soiling of feathers around the vent. Other
visceral organs were normal except for lack of fat around the base of the heart
and decreased myocardial tone. Impaction of the lower intestinal tract in these
birds most likely resulted from eating litter because of a change in feeding
regimen, which caused confusion and feed competition among male birds.
PMID- 17039853
TI - Predation as a cause of neurologic signs and acute mortality in a pheasant flock.
AB - A flock of approximately 15,000 ring-necked pheasants (Phasianus colchicus) was
evaluated for a sudden increase in mortality and acute neurological signs after
having been previously diagnosed 3 wk earlier with a chronic respiratory disease
of undetermined etiology. Approximately 25 live birds were displaying
neurological signs including circling, ataxia, and obtunded behavior and 50 birds
were dead. Three birds with neurological signs were submitted for evaluation.
Extensive subcutaneous hemorrhage over the head and penetrating puncture wounds
through the skull and into the brain were found. Trauma from a wild predatory
mammal, most likely the long-tailed weasel (Mustela frenata) that had invaded the
pheasant house and expressed surplus killing behavior was determined to be the
cause of the acute neurological signs and mortality. The relationship of the
chronic respiratory disease to the predation episode was not determined but it is
possible that pheasants with severe respiratory disease may have had increased
susceptibility to predation.
PMID- 17039854
TI - Micronutrients in women's reproductive health: I. Vitamins.
AB - Proper nutritional status of women before, during, and after pregnancy is an
important element of reproductive health. It maintains maternal health and
reduces the risk of adverse pregnancy outcome, birth defects and chronic disease
in children later in postnatal life. Pregnancy creates a special metabolic demand
for high-quality nutrients. With careful food selection, it is possible to obtain
most of the recommended levels of nutrients. Apart from the dietary intake,
nutrition is highly dependant on economic status, social and cultural
environment, and personal habits of the mother. Nutritional imbalance could cause
detrimental effects to the pregnant woman, influence pregnancy outcome, and
impair breast milk composition. Despite the extensive research, we still do not
have a complete understanding how nutritional status of the mother influences her
health as well as fetal growth and development. It is well known that fetal
growth and development is strongly linked with maternal supply of essential
nutrients, e.g. vitamins. The exact role of the variety of micronutrients in
fetal growth and development has yet to be explored in detail. It is estimated
that up to 30% of pregnant women suffer from a vitamin deficiency. Without
supplementation, about 75% would show a deficit of at least one vitamin.
Moreover, multivitamin deficit combinations often co-exist, and subclinical
depletations are probably common; consequences could be severe. Studies carried
on in developing countries have shown that improving micronutrient intake in
deficient women can reduce maternal morbidity and mortality. Also, proper
maternal intake of important micronutrients directly enhances the quality of
breast milk. To meet the increasing demands during pregnancy and the
breastfeeding period women should not be dependent only upon the dietary intake:
adequate reserve is essential for the successful pregnancy outcome.
PMID- 17039855
TI - Micronutrients in women's reproductive health: II. Minerals and trace elements.
AB - It is widely accepted that micronutrients have a major function in many periods
of women's life, particularly during pregnancy and lactation. Inadequate stores
or intake of micronutrients might have adverse effects both to the mother
(hypertension, anemia, complications of labor) and the fetus (congenital
malformations, pre-term delivery, intrauterine growth retardation). The effect of
improper nutrition is influenced by gestational age, severity of deficiency, or
both. Generally, the daily requirements in minerals and trace elements are easily
met in women having a balanced diet. Such diet during pregnancy should provide
the recommended daily allowance of all nutrients except elemental iron.
Consequently, deficiency states are supposed to be rare in developed countries,
and supplementation should be made on an individual basis. On the other hand,
nutritional deficiencies during pregnancy might be difficult to detect. Studies
from developing countries where micronutrient malnutrition is common during
pregnancy gave us strong evidence that supplementation of certain trace elements
and minerals could prevent some of the most severe adverse pregnancy outcomes.
While some micronutrients have been studied extensively (e.g. calcium, iron,
zinc, iodine), much less is known about others. It has been shown that multiple
micronutrient deficiencies, rather than single deficiencies, are common. Our
knowledge about the significance of interactions between micronutrients in
relation to pregnancy outcome is limited. The role of these interactions in
improving pregnancy outcome need to be investigated more precisely. According to
the summarized data, the potential benefits of routine supplementation seem to
outweigh any potential adverse reaction that can be attributed to their
consumption.
PMID- 17039856
TI - Menopacenutrient therapy: an alternative approach to pharmaceutical treatments
for menopause.
AB - Considerable controversy surrounds the use of hormone replacement therapy (HRT)
for treatment of peri-menopausal symptoms. Recent publications from three large,
prospective randomized studies call the safety of HRT into question, and leave
patients searching for answers. Nutrient therapy may provide symptomatic relief
without increasing risk of chronic disease. In this study, results of a series of
uncontrolled prospective studies of peri-menopausal symptom relief using Menopace
nutrient therapy were combined to provide a broad perspective on the safety and
effectiveness of this alternative treatment modality. Data from seven studies
with a total of 766 subjects were analyzed. Subjects with specific menopausal
symptoms reported improvement after three months of daily use of the therapy,
ranging from 87.8% of subjects with hot flashes to 67.5% of subjects with poor
concentration reporting improvement. Overall improvement in menopausal symptoms
was reported in 93.2% of all subjects. These results provide consistent evidence
of the effectiveness of comprehensive, nutritionally balanced nutrient therapy
for treatment of menopausal symptoms. While most evidence-based practitioners
focus primarily on research results from randomized, controlled clinical trials,
other forms of research evidence can also guide clinicians searching for safe and
effective treatment options for their patients.
PMID- 17039857
TI - Does the use of folic acid increase the risk of twinning?
AB - The increased rates of twinning and the increased consumption of folic acid are
two parallel processes described in recent years. However, the possible
association between an increased incidence of twin pregnancies and
periconceptional folic acid supplementation remains controversial. Whereas the
data indicating that when folic acid levels are increased to the range required
for reducing the incidence of neural tube defects, the data pertaining to the
increase in twinning rate are significantly incoherent and are flawed by serious
confounders, such as fertility treatments and maternal age. The only plausible
theory connecting methyltetrahydrofolate reductase mutation, folic acid, and
twinning has not been confirmed. In addition, temporal and dose-effect
relationships have not been established. Because of the lack of coherence,
questionable plausibility, and no clear dose-effect and temporal relationships, a
cause (folic acid supplementation) and effect (increased twinning rate)
association cannot be, at present, accepted. Thus, the established policy of peri
conceptional folic acid supplementation to reduce the incidence of neural tube
defects should be continued.
PMID- 17039858
TI - Rate of blastocyst development from excess embryos remaining in culture after day
3 embryo transfer.
AB - OBJECTIVE: To assess the rate of blastocyst development (BDR) from embryos
remaining in culture after day-3 embryo transfer (ET), and its relationship to
cause of infertility. STUDY DESIGN: Retrospective cohort study in tertiary-care
IVF Center. Blastocyst development rate (BDR) after day-3 ET was assessed in 126
women who underwent either conventional IVF or ICSI. RESULTS: Mean age, early
follicular FSH levels, number of 2PN zygotes, number of excess embryos, and
number of ET were similar between patients that underwent IVF and ICSI. Overall,
20% of extra embryos from conventional IVF patients developed into blastocysts
compared to 14% of embryos obtained from ICSI. Cause of infertility did not
affect BDR, even in patients who required ICSI due to male factors. CONCLUSIONS:
Low rates of blastocyst development from excess embryos are similar between IVF
and ICSI patients. Only 15 to 25% of excess embryos left in culture develop into
blastocysts, regardless of cause of infertility. Physicians and patients can use
this information to adjust both AR treatment protocols and patient expectations.
PMID- 17039859
TI - SUMEVA, a new system of climacteric symptom evaluation, and its correlation with
FSH and estradiol levels.
AB - OBJECTIVE: To evaluate a new climacteric symptom scale (SUMEVA) and to assess its
correlation with follicle stimulating hormone (FSH) and estradiol (E2) levels.
METHODS: 115 healthy perimenopausal women who were not receiving, nor had
received, hormone therapy were studied. They were asked to complete 3
questionnaires concerning climacteric symptoms: (1) Kupperman's index (KI), (2)
Green scale (GS), and (3) SUMEVA, which is the sum of symptom evaluations done in
an analog visual scale. FSH and E2 determinations were done by chemoluminiscence.
STATISTICAL ANALYSIS: The comparison among the groups was done by Student's t
test. Pearson correlation analysis was done between FSH and E2 levels and KI, the
GS, and SUMEVA. RESULTS: There were 60 women with FSH < or = 30 mIU/mL (group I)
and 55 with FSH > 30 mIU/mL (group II). The KI average in the whole group was
13.2 +/- 8.1, the GS 20.6 +/- 13.1, and the SUMEVA 65.6 +/- 44.9. The three
scales had a significant correlation between them. CONCLUSIONS: No correlation of
KI, GS, or SUMEVA was found with FSH and E2 levels, but the SUMEVA was as
effective as the other previously validated, scales for climacteric symptom
evaluation.
PMID- 17039860
TI - Characterization of dental fillings found in skulls from individuals buried in
San Jeronimos Church, New Spain: historical and archaeological evidences.
AB - Repair of teeth during the XIX century was often a very costly and painful
procedure. During this period, restoration of teeth was a procedure limited only
to those who could afford such care. In this study we analyzed teeth from a skull
sample found in San Jeronimo's Church. The characterization of molar fillings was
made with techniques such as X-ray fluorescence, X-ray diffraction and electron
microscopy. The purpose of this investigation was to establish technical
procedures for analysis, and to discuss the results within the context of the
socioeconomic status of these individuals and the written descriptions of the
dental practice during the XIX century.
PMID- 17039861
TI - Leroy E. Burney, MD, MPH: quiet champion of American dentistry and dental
research at mid-century.
AB - Leroy E. Burney was a preeminent Surgeon General and was recognized for
modernizing the Public Health Service. He promoted environmental public health
and access to health care for the poor. He oversaw major expansion of health
professions' education and research, and he was the first public official to
alert America to the link between cigarette smoking and lung cancer. Historical
accounts of Burney's legacy have not focused on his remarkable contributions to
dental public health. The aim of this study was to elucidate Burney's role over
four decades in promoting the interests of dentistry in America, through his
support of dental science, dental education, and public access to dental health
services. Burney engaged in dental research and developed a model dental public
health program for Indiana. As Surgeon General, he oversaw dramatic expansion of
dental research and education and the building of the National Institute for
Dental Research. A skillful collaborator, Burney worked toward common goals with
leaders of American dentistry and Congress. He was one of the few physician
members of the Trustees of the American Fund for Dental Education. A humble man,
Burney was a quiet champion of American dentistry and dental research for almost
forty years.
PMID- 17039862
TI - Benjamin Franklin and the dentist: the story of R. C. Skinner.
AB - Among Benjamin Franklin's papers was a letter from a young British immigrant, R.
C. Skinner, asking for a loan of only twenty dollars to help this young man begin
the practice of dentistry in this country. Although we don't know what the great
man's response was to this appeal, Skinner went on to achieve fame in his
profession. He was the first dentist ever, in this country, to be appointed to a
hospital staff; he established the first free dental clinic for the poor; and he
authored the first book on dentistry ever published in America, earning him the
title "The Father of American Dental Literature." From a newspaper advertisement
of 1794, further information has been gleaned about Skinner's practice: he not
only did conventional dentistry, but also supplied missing eyes, ears, noses and
legs. This was a forerunner of the contemporary subspecialty of prosthodontics
termed "maxillofacial prosthetics". An interesting list of Skinner's services and
his fees for each, gives us a good picture of what dentistry was like in Colonial
America.
PMID- 17039863
TI - The students of Edward Hartley Angle, the first specialist in orthodontics: a
definitive compilation.
AB - Edward Hartley Angle, MD, DDS, (1855-1930) was ardent in making orthodontics a
distinct specialty. In 1900, he founded the first school in the world devoted to
specialty training in orthodontics, the Angle School of Orthodontia in St. Louis,
Missouri. Over the next 30 years, the Angle School moved from St. Louis to New
York City to New London, Connecticut, and finally to Pasadena, California. There
was always some uncertainty regarding the accuracy of lists of graduates of the
Angle School, since the associated prestige was often a lure for false
representation by some practitioners. The purpose of this article is to delineate
an authoritative list of Angle's students. Recent additions to primary source
material help in reconstructing Edward Angle's seminal educational contributions.
From 1900 to 1930, Angle taught orthodontics to 198 students of which 185
received certificates of course completion. The remaining 13 received some
training from Angle, but did not complete his formal course for a variety of
reasons. He was highly selective in choosing the best dentist-students. Among his
students were 8 women, 6 Canadians and 27 from 15 countries outside North
America. Angle's graduates invariably became worldwide leaders and contributors
in orthodontics in the first half of the 20th century.
PMID- 17039864
TI - Gleanings about dentistry from the world of literature (thirty-seventh in a
series).
PMID- 17039865
TI - Dentistry on stamps. Chewing gum.
PMID- 17039866
TI - The Thomas W. Evans Museum and Institute revisited. 1907.
PMID- 17039867
TI - Renee Reijo Pera. Infertility researcher, UCSF.
PMID- 17039868
TI - Getting back on track.
PMID- 17039869
TI - Science and the gender gap.
PMID- 17039871
TI - [Study on melanin from taihe silky fowl and its complexes with Cu2+, Fe3+ ions by
IR spectrum].
AB - OBJECTIVE: The interaction between Cu2+, Fe3+ and Melanin from Taihe Silky fowl
for different pH values was investigated in heterogeneous system. METHODS: The IR
spectrum of melanin and its complexes with Cu2+, Fe3+ ions was determined.
RESULTS: The carbonyl group of melanin may interact with metals. CONCLUSION:
Taihe Silky fowl melanin is the mixture of pheomelanin and isomelanin.
PMID- 17039870
TI - [Preliminary study on the characteristics of Bupleurum chinense in nutrition
uptake].
AB - It was studied that the characteristics of Bupleurum chinense DC. in nutrition
uptake based on potted and field experiment to provide a properly fertilizer
application measure. The result showed that the absorption amounts of N, P and K
were in the order of K > N > P under field condition. For one-year-old B.
chinesnse DC., the average N, P2O5 and K2O absorption per 100 kg dry matter of
root were 11.77 kg, 2.43 kg, 14.07 kg respectively; for two-year-old, the average
N, P2O5 and K2O absorption amount per 100 kg dry matter of root were 12.11 kg,
2.74 kg, 18.39 kg respectively. The total absorption amount of N, P2O5 and K2O
were lower in the first year, while the percentage of content was higher, that
was to say, the demand for N, P and K was urgent in the first year. The
accumulation peak of N, P2O5 and K2O occurred regreening to later elongation
stage in the second year. The ratio of N, P and K were differential in different
growth stages.
PMID- 17039872
TI - [The analysis on processed chrysanthemum by FTIR spectrums second-order
derivative spectrums and two-dimensional spectrums].
AB - Using Infrared spectrums, Second-order derivative spectrums and Two-dimensional
spectrums to analyze Chrysanthemum and processed Chrysanthemum in henan province,
the infrared characters of Chrysanthemum and processed Chrysanthemum can be
found.
PMID- 17039873
TI - [Study on the TLC-fingerprint of Xiatianwu].
AB - OBJECTIVE: To develop a method that can well evaluate the quality of Xiatianwu.
METHODS: Methods are researched and discussed to construct the TLC-FP (thin-layer
chromatography finger-print) of Xiatianwu to evaluate its quality. RESULTS: The
areas of six evident peaks in the thin-layer chromatography of Xiatianwu are
compared with the area of dl-tetrahydropalmatine peak companied with them in the
same chromatography. The Rr of every peak and its relative area were acquired to
evaluate the quality of Xiatianwu and identify it. CONCLUSION: The TLC
fingerprint of Xiatianwu can well evaluate the quality of Xiatianwu.
PMID- 17039874
TI - [The identification of microscopic, physical and chemistrical analysis on
Curculigo orchiode and its counterfeit].
AB - OBJECTIVE: To identify sham Curculigo orchiode from the genuine. METHODS: Using
the distinguishing method of morphology and histology, TLC and UV spectrum
analysis. RESULTS: The tissue structrue, the physical and chemical featrures of
Curculigo orchiode and its counterfeit have obvious differences. CONCLUSION: The
counterfeit of Curculigo orchiode come from Paeonia lactifora's axillary root.
PMID- 17039875
TI - [Chemical constituents from the south China sea gorgonian coral Subergorgia
reticulata].
AB - Nine compounds, cholesterol (1), ergostra-7,22-diene-3beta, 5alpha, 6beta-triol
(2), cholesta-7,22-diene-3beta, 5alpha, 6beta-triol (3),5,8-epidioxycampesta-6,22
dien-3-o1 (4), batyl alcohol (5), theine (6), thymine (7), uracil (8), guanine
(9), were isolated from the South China Sea gorgonian coral Subergorgia
reticulata and their structures elucidated on the basis of spectral data. All of
these compounds were isolated for the first time from this gorgonian coral.
PMID- 17039876
TI - [Study on the chemical constituents of Mitragyna rotundifolia].
AB - Twelve compounds were isolated from the EtOAc-soluble and ButOH-soluble portions
of the EtOH extract from the bark of Mitragyna rotundifolia. These compounds were
identified by their spectral data as dauricine (1), 3,4-dihydroxybezoic acid (2),
beta-sitosterol (3), scopleton (4),3,4,5-trimethyoxyphenol-1-glucopyranoside (5),
taraxerol (6), 4-hydroxy-3-methyloxybenzoic acid (7), 3-hydroxy-4
methyloxybenzoic acid (8), caffeic acid (9), gambirine (10), gambireine (11),1,1
dimetheyl-2-acetl-diethyl ether (12), respectively. All compounds were isolated
from this genus for the first time.
PMID- 17039877
TI - [Studies on phloroglucinol derivatives of Dryopteris fragrans L].
AB - OBJECTIVE: To study the phloroglucinol derivatives of Dryopteris fragrans.
METHODS: Isolation and purification were carried out on repeated silica gel,
Sephadex LH-20 column chromatography and prepare HPLC. The structures of the
compounds were determined by physicochemical properties and spectral analysis.
RESULTS: Four compounds were isolated and identified as aspidin PB (I),
dryofragin (II), aspidinol (III), aspidin BB (IV). CONCLUSION: Compounds IV is
isolated from this plant for the first time.
PMID- 17039878
TI - [Studies on the chemical constituents of essential oil of Hunan Artemisia annua].
AB - The chemical constituents of the essential oil of Hunan wild Artemisia annua L.
in Xuefeng mountain region have been studied by means of the GC-MS. The essential
oil was extracted from Artemisia annua L. by steam distillation. The chemical
constituents were separated and identified by GC-MS, and the relative contents of
them in the oil were determined with area normalization method. Forty-five
components were separated and identified which accounted for 90% of total
essential oil. These components identified from the essential oil indicate that
Hunan wild Artemisia annua L. in Xuefeng mountain region is a good medical plant,
and worth to exploiting.
PMID- 17039879
TI - [Deterimination of schisandrin in Kadsura heteroclita (Roxb.) Craib by RP-HPLC].
AB - OBJECTIVE: To develop a method of RP-HPLC for determination of schisandrin
content in Kadsura heteroclita (Roxb.) Craib. METHOD: RP-HPLC analysis was
carried out by using Kromasil C18 column (5 microm, 250 mm x 4.6 mm) and methanol
water (65:35) as the mobile, and the detection wavelength was 250 nm. RESULTS:
The method was linear in the range of 0.08-0.06 nicrog (r = 0.9998), and the
average recovery was 100.24%, with the RSD of 2.09% (n=5). CONCLUSION: The method
was simple, accurate, highly sensitive and reproducible. It may be used for the
quantitative determination of schisandrin in extract of Kadsura heteroclita
(Roxb.) Craib.
PMID- 17039880
TI - [Harmine induces apoptosis in human SGC-7901 cells].
AB - OBJECTIVE: [corrected] To investigate the effect of apoptosis induced in human
SGC-7901 cells by Harmine. METHODS: The effect of Harmine on human SGC-7901 cell
survival and apoptosis was determined by MTT assay, light microscopy and flow
cytometry. Cell genomic DNA was detected by agarose electrophoresis. RESULTS: The
survival of human SGC-7901 cells decreased; Apoptotic cells were observed by
fluorescent microscope; FCM analysis showed that the peak of apoptosis increased.
Typical DNA Ladder were detected in DNA agarose gel electrophoresis. CONCLUSION:
HM can induce apoptosis in human SGC-7901 cells.
PMID- 17039881
TI - [The study on angiogenesis activity of danggui, chuanxiong and danshen].
AB - OBJECTIVE: To observe the effect of danggui (Radix angelicae sinensis),
chuanxiong (Rhizoma chuanxiong) and danshen (Radix salvae miltionrrhizae) on
cardiac microvascular endothelial cells (CMECs) obtained from rat and
quantitation of vessels on chick embryo chorioallantoic membrane (CAM) model.
METHODS: Normal rat cardiac microvascular endothelial cells (CMECs) were cultured
by collagenase and trypsin and the influences of the herbs on the CMECs were
observed by cell count and MTT colorimetry. The activity of blood vessels was
determined by quantitation of vessels on chick embryo chorioallantoic membrane
(CAM) model. RESULTS: Compared with the normal group, after treatment with
chuanxiong of high dosage, danggui of high and middle dosages, danshen of high
and middle and low dosages, they enhanced proliferation significantly (P < 0.05).
The two later could be in dependent dose. And the herbs might increase
quantitation of vessels on CAM. CONCLUSION: These Chinese herbs may promote
angiogenesis by stimulating proliferation of CMEC and incresasing blood vessels.
PMID- 17039882
TI - [Effect of the ethyl acetate extract of zhi ju zi on serum makers and the
expression of TGF-beta1 in rats with hepatic fibrosis].
AB - OBJECTIVE: To study the effect of the Ethyl Acetate Extract of Zhi Ju Zi on
hepatic fibrosis. METHODS: Model of liver fibrosis in rats was induced by CCl4.
The level of hyaluronic acid (HA) and laminin (LN) was detected by RIN. The
expression of TGF-beta1 of the rat liver was detected by RT-PCR. RESULTS: After
treatment, the level of HA was apparently decreased (P < 0.05); the level of LN
wsn't apparently different with the Colchicin group (P > 0.05); The expression of
TGF-beta1, was apparently decreased (P < 0.05) CONCLUSION: The Ethyl Acetate
Extract of Zhi Ju Zi can effectviely decrease the level of serum markers of
hepatic fibrosis and the expression of TGF-beta1.
PMID- 17039883
TI - [Studies on extraction process optimization of Panax notogingseng saponins].
AB - OBJECTIVE: To optimize the conditions for the extraction of panax notogingseng
saponins (PNS). METHODS: After selected extraction solvent and suitable particle,
we employed orthogonal experimental design to examine the conditions for the
extraction by determination of PNS. RESULTS: Significant effect was observed only
in extraction times. CONCLUSION: The optimum condition for extraction of PNS was
to extract panax notogingseng (Burk.) F. H. Chen with 10 times 70% ethanol for
1.5 hours for 3 times.
PMID- 17039884
TI - [The extraction, purification and assaying of Gynostemma pentaphyllum
polysaccharides].
AB - By orthogonal design, and considering extracting efficiency and cost, optimizing
the extract method of Gynostemma pentaphyllum polysaccharides. We purified the
crude Gynostemma pentaphyllum polysaccharides initially, and assayed the
polysaccharides content of Gynostemma pentaphyllum polysccharides. The content of
Gynostemma pentaphyllum polysaccharides was sigificantly higher than the
predecessor. It would provide conditions for the deep exploitation of Gynostemma
pentaphyllum.
PMID- 17039885
TI - [Research on extracting process for compound shenzhutiaozhi capsule].
AB - OBJECTIVE: The technics of optimal extraction for compound shenzhutiaozhi capsule
is investigated in this study. METHODS: Orthogonal test were employed for
selecting the optimum of extraction technics and the contents of oleanolic acid
and salvianolic acid B were detected by TLC-scanning and HPLC, respectively.
RESULTS: Five volume of 70% alcohol, extracting 3 times with half an hour for
each time, and seven volume of water, extracting 3 times with half an hour for
each time were considered the optimum extraction technics of Frugtus Ligustri
lucid, Salvie miltiorrhizae as well as Reizaoma Atractylodis Macrocfphalae,
respectively. CONCLUSION: The considerable extraction rate of active components
in the drugs is achieved by applying the selected technics.
PMID- 17039886
TI - Research progress on anti-diabetic Chinese medicines.
AB - Diabetes mellitus (DM) is commonly known as Xiaokezheng ([Chinese characters: see
text]) with respect to the sign of imbalance of yin, yang and qi in the
traditional Chinese medical system. This review is mainly focused on peer
reviewed international journals in chemistry, pharmacological and clinical
research of Chinese medicines (CM) used in therapeutic treatments of DM and its
complications. This article will also discuss the advantages and future
perspectives of anti-diabetic CM.
PMID- 17039887
TI - [The effect of shanzha xiaozhi capsule on the blood lipid and the function of
endothelial cells in patients with dislipide mia].
AB - OBJECTIVE: To explore the Mechanism of Shanzha xiaozhi Capsule improving the
functions of endonthelial cells in patients with dislipide mia. METHODS: To
measurate the blood lipid and the levels of plasma Endothelin (ET) and nitrodi
oxide (NO) in 30 patients with dislipide mia before and after taking the Shanzha
xiaozhi Capsule, and there were 10 normal persons in control group, which were
measured the blood lipid and the levels of ET and NO only one time. RESULTS:
After treatment with Shanzha xiaozhi Capsule, the levels of triglyceride (TG),
total cholesterol (TC), low density lipoprotein cholestero (LDL-C), ET were
markedly reduced (P < 0.05), and the levels of NO were obviously elevated (P <
0.05). CONCLUSION: Shanzha xiaozhi Capsule can reduce blood lipid level and the
plasma ET levels, increase the NO levels and the protection to the functions of
endothelial cells which might be involved in the mechanisms of against
atherosclerosis.
PMID- 17039888
TI - [Tuberculosis--a permanent problem].
PMID- 17039889
TI - [Significance of ultrasonography of the terminal ileum in moderate Crohn's
disease].
AB - BACKGROUND/AIM: Crohn's disease (CD) is a chronic granulomatous inflammatory
disease of unknown etiology, involving any part of the gastrointestinal tract,
and frequently followed by extraintestinal manifestations. The use of
ultrasonography plays a significant role in diagnosing this disease, as well as
in monitoring the effects of the therapy. The aim of this study was to assess the
use of ultrasonographic diagnostics in the patients with moderate serious and the
mild form of CD. METHODS: The study involved 30 patients both sexes with CD of
moderate form determined using the standard diagnostics, according to the Crohn's
Disease Activity Index--CDAI ranging from 220-400. The patients were divided into
two groups with CDAI > 320 (Ia), and CDAI between 220 and 320 (Ib), respectively.
The Control group was made of 19 patients with the mildly active stage of the
disease and the CDAI values in the range from 100-220. The patients were
submitted to an ultrasonographic examination of the terminal ileum affected with
CD in order to determine the length of the affected segment of intestine, the
thickness of the wall, the changes of the structure of the wall, the changes of
the surrounding mesenterium with the enlarged lymph nodes. CD complications,
abscesses, and enteroenteral fistulas were investigated, too. RESULTS: The
comparison of the ultrasonographic findings of the three groups revealed that
more serious clinical-laboratory image of CD significantly correlated with the
higher length of the affected segment (p < 0.001), higher thickness of the wall
(p < 0.001), the higher number and the larger lymph nodes of the mesenterium (p <
0.001). Only the most serious patients were found to have abscess of the
ileocecal area (Ia - 40%). There was no difference found between the groups
regarding the occurrence of enteroenteral fistulas. CONCLUSION: Considering the
obtained results and data from the literature, it could be concluded that an
ultrasonographic examination of the ileocecal area plays an important role in the
diagnostic procedure in the management of a patient with CD. Of particular
significance is the possibility to use this examination in monitoring the effects
of the therapy in patients with CD.
PMID- 17039890
TI - [Roentgencraniometric evaluation of the craniofacial dimensions in subjects with
symptoms of temporomandibular disorders].
AB - BACKGROUND/AIM: The aim of this study was to evaluate the possible association
between certain morphologic features of the craniofacial skeleton and the
presence of symptoms of temporomandibular disorders in young subjects with
natural dentitions. METHODS: The investigation was carried out on 80 lateral
cephalometric radiographs of two groups of male and female subjects between 18
and 25 years of age with natural dentitions. The analysed group consisted of 30
subjects with symptoms of temporomandibular disorders, and the control group of
50 subjects without such symptoms. According to the values of the ANB angle
(position of the maxilla with the mandible-Steiner cephalometric analysis) all
subjects were classified in the skeletal class 1. The roentgencraniometric
analysis of cephalometric radiographs included the evaluation of 25 linear
dimensions which values were compared between the examined groups and with the
values of the same dimensions in the Bolton standards for 18 years of age.
RESULTS: The results of this study confirmed the presence of significant
differences between the examined linear dimensions in the Bolton standards and
the same dimensions measured in the subjects of the analysed and the control
group. The comparative analysis of these values between the groups confirmed the
presence of significant differences in following linear dimensions at the level
of p < 0.00: S - Cs(Go), Mol - PP, Mol - MP and Ar - Go. CONCLUSION: Significant
differences between the examined linear dimensions measured in the subjects
included in this study and the same dimensions in the Bolton standards can be
explained by specific morphologic features of the craniofacial skeleton in people
of our population. Within the limitation of this study, the minor differences in
the values of the examined linear variables between the subjects of the
experimental and the control group can not be accepted as indicators of disturbed
function of the orofacial system.
PMID- 17039891
TI - [Use of the modified Fries technique in the reconstruction of the lower lip after
the removal of a malignant tumor].
AB - BACKGROUND/AIM: Lip carcinoma makes about 1/4 of all oral carcinomas. Primary
treatment of the lower lip carcinoma means radical excision of the full thickness
of the lower lip tissue together with the tumor. The reconstruction of the defect
accomplished after the removal of the lower lip tumor is a challenge for the
surgeon and requires a detailed preoperative planning, the right choice of the
method for reconstruction and the knowledge of the adequate surgical techniques
needed. The aim of this study was to presenta ten-year clinical results and
experience concerning the reconstruction of lower lip defects longer than 4 cm by
means of the modified Fries method in patients treated for the lower lip
carcinoma. METHODS: The reconstruction of the lower lip by means of the modified
Fries method was performed in 37 patients. The following parameters were
analyzed: sex, age, the time elapsed from the occurrence of the first symptoms
until the first consultation with the doctor, the size of tumors, the size of the
postexcision defect, TNM classification, the application of side diagnostic
procedures, pathohistological diagnosis of postoperative complications. The
sensibility of the lower lip region was monitored, as well as the obtained
esthetic effects. RESULTS: The results classified according to the mentioned
parameters were processed, analyzed and displayed in detail. Clinical experience
concerning the application of this reconstruction technique was presented and
analyzed. CONCLUSION: The modified Fries technique can successfully be applied in
the reconstruction of the lower lip defects longer than 4 cm because its
application leads to satisfactory functional and acceptable esthetic results.
PMID- 17039892
TI - [Methods of the physical medicine therapy in prevention of heterotopic
ossification after total hip arthroplasty].
AB - BACKGROUND/AIM: In the prevention of periarticular heterotopic ossification (HO),
a common complication after total hip arthroplasty (THA), nonsteroidal
antiinflammatory drugs (NSAID) and irradiation are used. Some theories presume
that local hypoxia of the soft tissue causes HO. The aim of this study was to
investigate if the early use of pulsed electromagnetic fields (PEMF) could
prevent this ossification since it accelerates the circulation and oxigenation of
soft tissue. METHODS: The study included three groups of the patients with
primary THA. The group C consisted of 66 patients/79 hips who had only
kinesitherapy in postoperative rehabilitation. The group B consisted of 117
patients/131 hips who had PEMF and interferential current (IC) which, on average,
started on the 14th day after the surgery combined with the standard
kinesitherapy. The group A consisted of 117 patients/131 hips who had PEMF from
the third postoperative day and IC from, on average, the 14th postoperative day
with the standard kinesitherapy. The classification of HO was done on a standard
AP roentgenograms of the hips, taken at least one year after the surgery.
RESULTS: The overall HO was seen in 50.63% of the group C patients, in 43.51% of
the B group and in 16.67% of the group A. Severe HO (III and IV class according
to Brooker) was seen in 26.58% of the group C patients and in 6.10% of the group
B, but none in the group A. CONCLUSION: According to the obtained results an
early treatment with PEMF could prevent severe HO and reduce the overall HO.
PMID- 17039893
TI - [Analysis of loss of heterozygosity of the tumor suppressor genes p53 and BRCA1
in ovarial carcinomas].
AB - BACKGROUND/AIM: Among the genes involved in ovarian carcinogenesis, there has
been increased interest in tumor-suppressor genes p53 and BRCA1. Both of the
genes make control of cell cycle, DNA repair and apoptosis. The p53 is a "genome
guardian" inactivated in more than 50% of human cancers, while BRCA1 mutations
are found mostly in breast and ovarian cancer. The aim of this investigation was
to establish the frequency of loss of heterozygosity (LOH) in the regions of the
genes p53 and BRCA1 in ovarian carcinomas, and to analyze the association of LOH
with the disease stage and prognosis. METHODS: We analyzed 20 patients with a
confirmed diagnosis of epithelilal ovarian carcinoma. DNA for molecular-genetic
analysis was extracted from the tumor tissue and blood as normal tissue of each
person. Microsatellite markers of the regions of genes p53 and BRCA1 were
amplified by PCR method. The determination of allelic status of microsatellites
and detection of LOH was performed after PAA gel electroforesis. RESULTS: Both of
the analyzed microsatellite markers were informative in 13/20 (65%) cases. In the
region of gene p53, LOH was established in 4/13 (30.7%) tumors. One of them had
histological gradus G1, one had gradus G2, and two of them had gradus G3, while
all were with the International Federation of Gynecology and Obstetrics (FIGO)
IIIc stage. In the region of gene BRCA1, LOH was detected in 5/13 (38.5%) tumors.
Four of them had histological gradus G2, and one had gradus G3, while by the
(FIGO) classification one was with stage Ib, one was with stage IIIb, while the
three were with stage IlIc. LOH in both of the analyzed regions was detected in
one tumor (7.70), with histological gradus G3 and the FIGO IIIc stage.
CONCLUSION: The frequency of LOH in epthelial ovarian carcinomas was 30.7% and
38.5% for p53 and BRCA1 gene regions, respectively. Most of tumors with LOH had
histological gradus G2 or G3, and the clinical FIGO stage IIIc, suggesting the
association of this occurrence with a later phase of the disease.
PMID- 17039895
TI - [Pulmonary barotrauma].
PMID- 17039894
TI - Histopathology of chronic hepatitis C in relation to virus genotype.
AB - BACKGROUND/AIM: The natural history of hepatitis C virus (HCV) infection is
variable and the factors determining the course of the illness are unclear. There
are geographical variations in the distribution of different HCV genotypes, and
some of them are related to the specific infection routes. Regarding our country,
the dominant genotype is genotype 1b. It is unclear and still remains a question
whether the distinct histopathological manifestations are related to the
particular genotypes of HCV. Thus, the aim of this study was to determine whether
the distinct histopathological manifestations of HCV infection might be in
relation to the individual virus genotype. METHODS: In this study we examined 126
patients with chronic HCV infection regarding the histopathological features,
demographic data, and virus genotype. The observed groups of patients were
predominantly infected with HCV genotypes 1b and 3a. RESULTS: In this study we
found that the patients infected with HCV genotype 1b had more frequently
moderate or severe necroinflammatory activity of the disease, significantly
higher grading score as compared with other genotypes (p < 0.0001). A higher
degree of fibrosis was, also, more common in the patients infected with genotype
1b of HCV as compared with other genotypes (p < 0.05). There were no significant
correlations between the necroinflammatory activity of the disease and the stage
of fibrosis in 1b, 4 and mixed genotypes. CONCLUSION: The present data support
the hypothesis that distinct genotypes of HCV are associated with the particular
histopathological manifestation of the disease.
PMID- 17039896
TI - [Second-line antitubercular agents and their adverse effects].
PMID- 17039897
TI - Long-term outcome of strabismus and ptosis surgery in a mother and daughter with
congenital fibrosis of extraocular muscles.
AB - BACKGROUND: Congenital fibrosis of extraocular muscles (CFEOM) is a very rare
congenital condition, characterized by variable amounts of restriction of the
extraocular muscles, with or without ptosis. The aim of this report was to
describe a severe, atypical, exposure-induced corneal stromal lysis in two
patients. CASE REPORT: A mother and a daughter with a severe CFEOM were
presented. The surgery of both extraocular muscles and ptosis led to a fair
outcome in mother even 30 years after, and a very good outcome in daughter 4
years after the treatment. CONCLUSION: Though frequently challenging and
dissapointing the outcome of surgery of both extraocular muscles and ptosis in
CFEOM can be favorable even in rather severe cases. To the best of our knowledge,
the atypical keratolysis we described has not been highlighted in the literature
on CFEOM so far.
PMID- 17039898
TI - [Aggressive intraabdominal fibromatosis].
AB - BACKGROUND: Intraabdominal or mesenteric fibromatosis is a rare benign
nonmetastatic neoplasm that appears as a sporadic lesion or in patients with
familiar polyposis. Its evolution is unpredictable. About 10% of the cases shaw a
very aggressive growth. CASE REPORT: We presented a 22-year-old woman in whom an
aggressive intraabdominal fibromatosis had appeared during the first pregnancy as
a well circumscribed ovoid tumor, involving the terminal ileum, the caecum, the
ascending colon, the right kidney, the ureter, and the right common iliac artery.
The tumor was excised with right colectomy, nephroureterectomy and resection of
the involved artery using arterial reconstruction with graft interposition. Two
years after the surgery the patient developed an inoperable tumor recurrency with
a fatal outcome. CONCLUSION: In spite of a successful surgical excision during
the original surgery intraabdominal or mesenteric fibromatosis might have an
aggressive evolution leading to an inoperable tumor recurrency and a fatal
outcome.
PMID- 17039899
TI - [Abdominal compartment syndrome caused by ruptured abdominal aortic aneurysm in
vena cava].
AB - BACKGROUND: Abdominal compartment syndrome (ACS) is a rapid increase in intra
abdominal pressure asssociated with multi-organs dysfunction. It is caused mostly
by abdominal bleeding und massive volume compensation. CASE REPORT: We reported a
76-year-old patient admitted to the hospital with aortic abdominal aneurysm, 13.7
cm in diameter, ruptured in vena cava, which caused intraabdominal hypertension,
the liver and kidney dysfunction, as well as circulation, respiration and
metabolic disorders. Intraabdominal pressure was measured by bladder manometry.
Central venous pressure and systemic arterial pressure were monitored
continuously. Clinical signs were thrill and typical abdominal bruit. Aorto-caval
fistula was diagnosed by the use of contrast computerized tomography. Caval
endoaneurysmatic suture and aortobiiliac bypass with 18 x 9 mm Dacron prothesis
were performed. Haemodynamic changes were mostly corrected during the surgery.
The complete correction of haemodynamics, liver, kidney, respiration and
metabolic changes was established in the next few weeks. CONCLUSION: The ACS was
caused by rupture of abdominal aortic aneurysm in vena cava followed by edema of
the abdominal organs, retroperitoneum, abdominal wall and ascites. Caval
endoaneurysmatic suture and aortobiiliac bypass with 18 x 9 mm Dacron prothesis
solved aortocaval fistula as well as all the organs and metabolic dysfunctions
caused by ACS.
PMID- 17039900
TI - Global initiative for the prevention of blindness: Vision 2020--the Right to
Sight.
PMID- 17039901
TI - [Clinical trials of statins and fibrates --a meta-analysis].
AB - INTRODUCTION: Several clinical trials of hypolipidemics showed a decrease in
mortality by 30-40%, while others showed detrimental or no effects. The question
remains: which trial should be the basis of clinical decision making in the
choice of hypolipidemic therapy? MATERIAL AND METHODS: Meta-analysis is a method
for combining research results of several studies. Effects of statins and
fibrates with respect to placebo, were assessed by systematic literature review
and meta-analysis. Medline and CENTRAL databases were searched using the
following keywords: hyperlipoproteinemia, hypolipidemic agents and individual
drug names. The main inclusion criteria were as follows: statin or fibrate,
placebo controlled randomized trial, at least one year treatment on average, at
least 100 patients per study arm and reported mortality. RESULTS: Fibrates showed
almost complete absence of treatment effects on mortality with odds ratio of 0.99
and 95% confidence interval 0.80 - 1.11. The odds for statins were 0.87, 0.80 -
0.95. DISCUSSION: Despite the absence of treatment effects of fibrates, it is
noteworthy that inclusion criteria of early fibrate trials focused mainly on
cholesterol with recent identification of elevated triglycerides as an
independent risk factor. As fibrates exert the most pronounced effect on
triglycerides, they still may show effect in target populations. Effects of
statins are confirmed, but they are noticeably lower than in individual trials
which are given most publicity. CONCLUSION: Even after several decades of fibrate
use, conclusive evidence of their beneficial effects still needs to be elucidated
in appropriately designed trials. However, a beneficial effect of statins on
mortality decrease has been proven. Meta-analysis has an important role in
estimating true treatment effects and in the practice of evidence-based medicine.
PMID- 17039902
TI - [The probability of finding HLA identical or partially matched unrelated donors
in the population of Vojvodina].
AB - INTRODUCTION: Allogeneic bone marrow transplantation and hematopoietic stem cell
transplantation from unrelated donors are treatments of choice for patients
lacking HLA identical siblings or family matched donors. MATERIAL AND METHODS:
Class I HLA typing was performed by using a standard microlymphocytotoxicity test
in 434 unrelated persons from Vojvodina, while, class II HLA typing was performed
using a modified immunofluorescent technique. The estimated gene frequencies for
the populations of Crete, Korea, China, Scotland, Romania, and North America,
were used to calculate phenotype frequencies, the probability of finding HLA
identical or partially (in 5/6 HLA antigens) matched unrelated donors, the number
of donors necessary for research, as well as genetic distances between
populations. RESULTS: The probability of finding HLA identical or partially
matched unrelated donors for patients from Vojvodina is higher in closely related
populations with low genetic distances, such as populations of Crete, Romania and
Scotland. DISCUSSION: The probability of finding HLA identical or partially
matched unrelated donors is in inverse proportion with the number of unrelated
donors necessary for research with aim of finding at least one HLA compatible
donor. CONCLUSION: The probability of finding compatible unrelated donors depends
on the degree of HLA matching between the donor and recipient, HLA phenotype
frequencies and the donor pool size. These methodology may have a wider usage,
because it can be applied in calculating the probability of finding suitable
genotypically matched donors, by using HLA allele frequencies defined by
molecular techniques.
PMID- 17039903
TI - Cigarette smoking and lung cancer trends in Serbia--a ten-year analysis.
AB - Cigarette smoking is the single most common cause of morbidity and mortality in
the world, and the most important risk factor for developing lung cancer (LC). LC
is the most frequent form of cancer in men worldwide. Almost half of the adult
population in Serbia smokes. The aim of the study was to analyze the incidence
rate (IR) and trend of LC in Serbia from 1994 to 2003, with special regard to
tobacco smoking status (TSS). Referral annual reports of the Institute of Lung
Diseases and Tuberculosis on newly diagnosed cases of LC, categorized by sex and
TSS, have been analyzed TSS included three categories: smokers, ex-smokers and
non-smokers. LC IR showed an increasing tendency (RR: 0.2859) with 34/100,000
population in 2003, and significant differences among districts (6.3
39.1/100.000). Smokers, ex-smokers, and non-smokers account for 70.3%, 17% and
12.6%, respectively (p < 0.001). An increasing trend of female lung cancer was
evident in all three categories, but the most remarkable in smokers. There is a
clear and urgent need to inform the population on harmful effects of tobacco
smoking on health and risks for lung cancer.
PMID- 17039904
TI - [Chronic hepatitis C virus infection: is there a correlation between HCV
genotypes and the level of viremia?].
AB - INTRODUCTION: Hepatitis C virus (HCV) RNA status and HCV genotypes have become
extremely important for exact diagnosis, prognosis, duration of treatment and
monitoring of antiviral therapy of chronic HCV infection. MATERIAL AND METHODS:
For the purpose of precise and objective assessment of virologic analyses, such
as the determination of the number of virus copies and virus genotypes, 110
patients with chronic HCV infection were tested Genotyping of HCV isolates and
HCV RNA quantification were performed by using the PCR method. Genotype 1b
infection was verified in 49.1% of patients, genotype 3a infection was found in
28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections
were diagnosed in 9.1% of cases. RESULTS: Patients infected by genotype 1b had
significantly higher serum HCV RNA level in relation to patients infected by
other genotypes (p < 0.05). Over 70% of patients infected by genotype 1b had more
than 2 x 10(6) virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the
percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately
7.7 x 10(6) virus copies in 1 ml of blood, which was significantly higher in
comparison with female patients (2.3 x 10(6) copies/ml; p < 0.05). CONCLUSION:
Our results are in concordance with the results of other authors reporting that
genotype 1b is predominant in Europe, as well as significantly higher incidence
of viremia in patients with genotype 1b infection in relation to other HCV
genotypes. Based on these results, we can conclude that our patients, most
commonly, present with severe clinical course of chronic HCV infection and
require longer treatment (48 weeks), which causes economic problems.
PMID- 17039905
TI - [Antibiotic prescribing policy of the Republic Health Insurance Fund of
Montenegro in the period 2000 - 2004: effects of drug utilization reform
strategy].
AB - INTRODUCTION: Monitoring of antibiotic prescribing promotes rational use of these
drugs, reduces costs and slows down the progress of resistance. The objective of
present study was to analyze the effects of drug utilization reform strategy
realized by the Republic Health Insurance Fund of Montenegro, during the period
2000-2004. MATERIAL AND METHODS: This before-after comparative
pharmacoepidemiological study comprised a sample of 100% prescription only
antibiotics available in public pharmacies during the period 2000 - 2004. The
drug use was calculated using ATC/DDD methodology and Wilcoxon's test for matched
pairs was used in order to calculate the statistical significance of difference.
RESULTS: Antibiotic prescribing was approximately lower by 12% in 2004 in regard
to 2000 (12.80 vs. 14.57 DDDs, p > 0.05). The participation of this
pharmacotherapeutic group in the total drug dispensing has remained almost equal
(approximately 8%). The highest increase in prescribing was established for
macrolides (1.05 vs. 1.64 DDDs, 59%); penicillins were also prescribed more
frequently (6.41 vs. 6.56 DDDs, 2%), but other subgroups were prescribed less
frequently: cephalosporins--(23%) (3.11 vs. 2.43 DDDs) and quinolones--(63%)
(1.10 vs. 0.47 DDDs). CONCLUSION: The drug utilization reform strategy showed
mostly positive effects on antibiotic prescribing during the period 2000 - 2004.
Further educational activities are necessary in order to establish more rational
approach to prescribing and utilization of antibiotics.
PMID- 17039906
TI - [Microsatellite DNA analysis as a tool for forensic paternity testing (DNA
paternity testing)].
AB - MICROSATELLITE ANALYSIS: By using serological or HLA-testing, the alleged father
can be excluded as the biological father, but, regardless of the degree of
probability, positive paternity results cannot be obtained without DNA testing.
According to the results of the National Human Genome Project, human genome
consists of approximately 30.000 genes. The vast majority of human DNA is not
organized in genes and has no genetic expression or visible function. Non-coding
DNA contains genetic markers important for human identification. Short tandem
repeats, or STRs, are a class of microsatellites consisting of tandemly repeated
sequences of 2 to 6 base pair length monomers. Most of the microsatellites show a
high degree of polymorphism, which can be evaluated by PCR technique, and used in
criminalistics, forensic identification and parentage testing. A source of DNA in
parentage testing are blood samples or buccal swabs which are routinelly used.
Amplification of isolated DNA can be performed in 25-30 cycles by PCR, and
fragments are separated by capillary electrophoresis. CONCLUSION: The probability
of paternity of 99.99% or higher corresponds to the paternity "practically
proven", indicating that the alleged father is the biological father. Such
results can be obtained only by DNA testing. DNA-testing laboratories are
required to conduct validation of laboratory facilities, equipment and staff and
are subject to permanent control by the society.
PMID- 17039907
TI - [Attitudes of women and gynecologists towards voluntary sterilization in
Serbia?].
AB - INTRODUCTION: Voluntary sterilization is a very effective and safe birth control
method. Is it, however, accepted as a birth control method in Serbia? This is
certainly a question that should be explored, regardless of the fact that
voluntary sterilization is neither accessible nor promoted. MATERIAL AND METHODS:
The target group included women who decided to terminate their pregnancy, and
gynecologists from various parts of Serbia. RESULTS AND DISCUSSION: The survey
results indicate that more than half of women believe that voluntary
sterilization should be available in Serbia. Also, a large number of surveyed
women, almost half of them, would undergo voluntary sterilization. Younger women,
respondents with secondary education, those who gave birth to a desired number of
children, as well as those who have a good relationship with their partners,
those who have experienced a great number of induced abortions, namely those who
wish to use contraception in the future, are more open to voluntary
sterilization. The majority of gynecologists also think that voluntary
sterilization should become available in Serbia. Most of them consider
therapeutic and eugenic reasons as appropriate for surgical sterilization.
However, gynecologists lack current knowledge about this contraceptive method,
and would not accept to use voluntary sterilization themselves. CONCLUSION: The
reasons for individual nonacceptance indicate that many of the registered
ambivalent or negative opinions can be changed by spreading knowledge on
voluntary sterilization. Moreover, the knowledge of gynecologists about voluntary
sterilization should be improved as well.
PMID- 17039908
TI - [Natriuretic peptides and multimarker approach to risk stratification of patients
with acute coronary syndromes].
AB - NATRIURETIC PEPTIDES IN ACUTE CORONARY SYNDROMES: Brain natriuretic peptides
(BNP) and N-terminal prohormone brain natriuretic peptides (N-proBNP) have been
shown to provide important prognostic information in patients with acute coronary
syndrome (ACS). Ischemia may be an important stimulus for BNP release. This does
not imply, however, that BNP is useful for diagnosing ischemia, and BNP is
unlikely to prove sensitive or specific enough for this purpose. SIGNIFICANCE OF
NATRIURETIC PEPTIDES IN ASSESSING PROGNOSIS IN PATIENTS WITH ACUTE CORONARY
SYNDROMES: In patients with ST-elevation and non-ST-elevation myocardial
infarction, higher BNP and N-proBNP levels have been shown to predict a greater
likelihood of death or heart failure, independent of other prognostic factors.
THERAPEUTIC IMPLICATIONS OF BNP ELEVATION IN ACUTE CORONARY SYNDROMES: Patients
with BNP or NT-proBNP elevation following ACS are clearly at high risk for death
and for developement of heart failure, but specific therapeutic implications of
BNP elevation have not been defined. In particular, it is not known how patients
with BNP elevation should be treated considering the fact that they have normal
troponin levels and no clinical evidence of heart failure. MULTIMARKER STRATEGIES
FOR RISK STRATIFICATION IN ACUTE CORONARY SYNDROMES: It has been shown recently
that in patients with acute coronary syndromes the risk increased sequentially
among those with one, two or three elevated biomarkers. THERAPEUTIC APPLICATIONS
OF CARDIAC BIOMARKERS IN ACUTE CORONARY SYNDROMES: Multimarker strategies, that
incorporate panels of cardiac biomarkers, are likely to be used in the future for
risk stratification and for pathophysiologically-guided treatment of patients
with ACS.
PMID- 17039909
TI - [Predisposing factors of the migraine syndrome in children].
AB - INTRODUCTION: The aim of this paper was to define characteristics which could be
used to recognize groups of children at risk for migraine syndrome. MATERIAL AND
METHODS: Predisposing factors of migraine syndrome were investigated by
conducting a poll among 24.828 children aged 3-16, in Vojvodina, during the
period between 1988-2004. RESULTS: For the purpose of defining recognizable
characteristics of children with migraine syndrome, a comparison of children with
migraine headaches, non-migraine headaches, and those without headaches was done
among 24.828 children. Apart from direct heredity, the following factors should
be accepted as predisposing factors of migraine syndrome: child's order of birth
(second child), length of breast-feeding, age at which the ready-made industrial
food was introduced, as well as the age at which the child started the whole-day
stay (which is in inverse proportion to the risk of migraine attacks and the age
of the first symptoms), particularities in behaviour pattern, family social
status, atmosphere in the family, previous paroxysmal torticollis, episodic
vertigo of unknown etiology, recurrent abdominal pain, and lack of cerebral
hemisphere dominance. CONCLUSION: Children with migraine headaches have
particularities, not clear enough for the time being, but recognition of which is
necessary for early prevention of migraine syndrome in childhood.
PMID- 17039910
TI - [The prevalence of craniomandibular disorders in the military population of the
Republic of Serbia].
AB - INTRODUCTION: The aim of this study was to determine the prevalence of
craniomandibular dysfunction (CMD) in the military personnel of the Republic of
Serbia, as well as the distribution of sings and symptoms of CMD in this
population group. MATERIAL AND METHODS: The epidemiological investigation
included 284 male persons between 18 - 25 years of age. The sample consisted of
Military Academy students, and soldiers from different regions of the Republic of
Serbia. A questionnaire was designed using Helkimo's clinical dysfunction index
and sings and symptoms of CMD were evaluated, namely the anamnestic index (Ai)
and the dysfunction index (Di). RESULTS: According to the anamnestic dysfunction
index (Ai), 85% of persons among the examined group presented without any
symptoms of CMD (Ai = 0), 14% had mild symptoms (Ai =1) and 1% had severe
symptoms of CMD (Ai = 5). Functional analysis of the orofacial system in the
examined group (evaluation of dysfunction index - Di) revealed, however, that 70%
of solders had at least one sign of CMD, precisely a dysfunction index Di > 0.
The analysis of signs and symptoms of CMD revealed that disturbances in
mandibular kinematics were the most prevalent sign of CMD in this population
group, which was confirmed in 56% of examined persons. Disturbed functions of
temporomandibular (TM) joints (click, and reciprocal click, deviation and
deflection during mandibular opening) were established in 31% of examined
persons, and sensitivity of TM joints and masticatory muscles during palpation in
4% of examined persons. Pain during mandibular movements was established only in
1% of examined persons. CONCLUSION: The results of this investigation point to
significant prevalence of craniomandibular disorders in the examined population
group. The incidence of TMJ and masticatory muscle pain in 4% of examined persons
and of pain during mandibular movements only in 1% of examined persons, points to
presence of mild or initial types of CMD in this population group.
PMID- 17039911
TI - [Some psychological characteristics of children and adolescents with vitiligo-
our results].
AB - INTRODUCTION: Numerous studies have characterized patients with chronic skin
disease as psychologically vulnerable, mainly due to the fact that their
condition affects their social relations and all other aspects of life. The
purpose of this work was to determine whether there are significant differences
in the level of anxiety, severity of depressive symptoms, and presence of
stressful life events between adolescent patients with vitiligo and healthy
peers. MATERIAL AND METHODS: 33 patients with vitiligo aged 10-15 years, and a
control group of 60 healthy subjects of the same age, were included in this
prospective study. A clinical examination was performed to determine the clinical
types of vitiligo, estimate depressive symptoms using the Birleson Depression
Scale, and anxiety was evaluated by the Spielberger's scale (State-Trait Anxiety
Inventory). For determination of the frequency of stressful events, the Risk
Scale was used. RESULTS: Adolescents with vitiligo did not show more pronounced
signs of anxiety or depression than healthy subjects; differences were not
apparent in the Risk Scale either, considering stressful events. DISCUSSION AND
CONCLUSION: The lack of differences between the two examined groups might be due
to prepubertal age of the majority of subjects. 63.63% of all children included
in this study were in the prepubertal age (10-12 years), which is the period when
they are still not focused on their own body and changes to physical appearance.
It is possible that early onset of vitiligo is a "protective factor", enabling
the child to attain compensatory mechanisms to solve the problem of vitiligo
through various interests and aspirations, which do not depend on physical
appearance.
PMID- 17039912
TI - [Ultrasound diagnostics of atherosclerosis in chronic renal insufficiency].
AB - INTRODUCTION: Atherosclerosis is more frequent in patients with chronic renal
insufficiency than in general population. The aim of this study was to
investigate the frequency of atherosclerosis and risk factors in hemodialysis
patients. MATERIAL AND METHODS: We studied 62 patients (36 male and 26 female;
mean age, 56 +/- 13 years). The mean time on HD was 65.7 +/- 46.7 months. These
patient underwent the following examinations: assessments of risk factors, body
mass index, soft tissue calcification biochemical analyses and Duplex
ultrasonography of carotid arteries; RESULTS: In two thirds of patients older
than fifty years, thickening of the intima-media complex was found. No
statistically significant difference was found in the frequency of
atherosclerosis regarding sex, tissue calcification, plaque, smoking and Diabetes
Mellitus. There was no correlation between the thickness of the intima-media
complex and traditional risk factors for atherosclerosis. However, there was a
statistically significant correlation among atherosclerosis, age and time on
dialysis. Atherosclerosis was found in 68% of patients between the age of fifty
and seventy years. Duration of dialysis and age are statistically significant
factors for atherosclerosis.
PMID- 17039913
TI - [Treatment of knee flexion contracture in patients with chronic juvenile
arthritis--a case report].
AB - INTRODUCTION: Knee flexion contractures are common after-effects of juvenile
arthritis. Treatment is usually conservative and may include physical therapy and
kinesitherapy. Surgical treatment, particularly of the soft parts, indicated for
contractures resistant to conservative treatment, helps to correct the deformity,
maintain movements, and relieves pain. Intensive postoperative physiotherapy is
of special importance. CASE REPORT: A 23-year-old female patient with chronic
juvenile arthritis since the age of one was admitted for treatment of flexion
contractures in both knees, muscle hypotrophy, loss of strength and gait
disability. The patient underwent arthroscopic synovectomy. The operation was
first performed on the right and after 3 mouths on the left knee. The
preoperative range of motion in the right knee was 30 degrees - 70 degrees and in
the left 40 degrees - 80 degrees. The patient underwent intensive physical
therapy to reduce postoperative swelling of knees and firstly passive and then
active kinesitherapy. Nine months after the first surgery and six months after
the second, the range of motion in the right knee was 0 degrees - 100 degrees and
in the left 0 degrees - 105 degrees. The strength of tested muscles was increased
and gait was improved. CONCLUSION: Management and rehabilitation of patients with
chronic juvenile arthritis include maintenance or improvement in position and
function of joints that is achieved with synovectomy. The results depend on
combined interdisciplinary rehabilitation, well-experienced staff and pre- and
post-operative physiotherapy as well as kinesitherapy. Arthroscopic synovectomy
has many advantages and we believe that it was a better solution than open
capsulosynovectomy in this patient with chronic juvenile arthritis of the knee.
PMID- 17039914
TI - [Maternal and fetal death due to placenta previa/accreta in a concealed pregnancy
-a case report].
AB - INTRODUCTION: This is a case report of maternal and fetal death due to major
hemorrhage of a patients with placenta previa/accreta in a concealed pregnancy.
Bleeding is the leading cause of maternal mortality in obstetrics. Postpartum
hemorrhage is the most important cause of maternal death. Placenta accreta is a
severe complication involving an abnormal attachment to the uterine wall so that
it cannot be easily separated from the uterus. CASE REPORT: Due to the fact that
one part of the placenta is partially detached, while the other part has grown
into the uterus, postpartum hemorrhage may occur with lethal outcome, unless the
mother is hospitalized. Fetal death was caused by severe meconium aspiration. One
way to prevent such complications is to support legal abortions.
PMID- 17039915
TI - [Rene Favaloro--a surgeon who has changed the history of coronary disease].
AB - Rene Favaloro was one of the most distinguished surgeons of the 20th century. He
was the first to introduce the original technique of aortocoronary bypass
grafting, entering the new era of coronary artery disease treatment. Working at
the Cleveland Clinic, together with Mason Sones and Effler, he became a member of
the medical team which performered the first aortocoronary bypass grafting and
showed the functional competence of the new graft. Although today percutaneous
coronary interventions and coronary artery stents have a very important role in
coronary artery disease treatment, five years after his death aortocoronary
bypass grafting is the method of choice in selected groups of patients. Nowadays,
when urgent percutaneous coronary interventions are an important treatment option
in our country, it is good to remember that this also was the idea of Rene
Favaloro and Mason Sones, who discussed agressive treatment in the first hours of
myocardial infarction, and to remember his tremendous contributions and life
dedicated to cardiosurgery.
PMID- 17039916
TI - [Basic characteristics of duplex sonography in the assessment of lower limb
arterial circulation].
AB - INTRODUCTION: Dulpex and color duplex ultrasonography of lower limb arteries are
valuable non-invasive diagnostic methods in the pathology of vascular diseases
and a major step in diagnostics and in follow-up of hemodynamic and morphologic
characteristics. COLOR DUPLEX SONOGRAPHY: The method consists of image analysis
and analysis of Doppler information. Real-time-B mode is used to visualize the
anatomy of blood vessels and other pathological lesions. Doppler information
based on the Doppler effect determine the pulse wave i.e. the shape of flow
velocity--hemodynamic characteristics. Spectral analysis is the most important
element of Doppler examination of the lower limb peripheral arteries. Based on
the spectral analysis, there are four stages of lower limb arterial disease:
normal findings--1% - 19% diameter reduction; medium stenosis--artery diameter
reduction of 20% - 49%; high level stenosis--artery diameter reduction of 50% -
100%; occlusion--no flow detected within the imaged arterial segment. In the
first place, both iliac arteries are examined, which is followed with femoral,
popliteal and crural arteries. The examination of iliac arteries is carried out
with a 3.5 MHz transducer, and other peripheral arteries of the lower limbs are
examined with a 7, 5 or 5 MHz transducer. CONCLUSION: Color Doppler is an
extremely valuable diagnostic method in detecting pathology of the lower limb
arteries. With high reliability level arterial insufficiency and pathological
arterial segments are diagnosed by a duplex-Doppler.
PMID- 17039918
TI - [Clinical appearance and outcome of zone 1 retinopathy of prematurity (ROP)].
AB - The goal of this clinical trial was to evaluate outcomes of the treatment of
retinopathy of prematurity (ROP) located in zone 1 (Zone 1 ROP). This disease has
a specific clinical appearance and poor prognosis. Usually it is difficult to
identify particular stages of ROP and to indicate treatment while following
progression of the disease. In the group of zone 1 ROP it is necessary to
separate transient forms (TF), in which vascularizations reach edges of zone 2,
from very posterior forms (VPR), in which vascularizations and pathological
changes are present only in zone 1. There were 24 eyes with zone 1 ROP (15
children) treated with combination of transcleral laser photocoagulation and
cryotherapy during the years 2000 till 2005 in our series. Five eyes suffered
from VPR, 19 eyes from TF. Average follow -up was 24 months. We found better
outcomes in eyes with TF treated in pre-threshold stage of ROP (10 eyes) than in
threshold stage of ROP (9 eyes). All 5 eyes with VPR developed unfavourable ROP
stage IV or V. Zone 1 ROP becomes diagnostic and therapeutic challenge
considering growing incidence of surviving of newborns with low or very low birth
weight. Treatment initiation during prethreshold stage of ROP as it is supported
by ETROP study (Early treatment of ROP) seems to be promising.
PMID- 17039917
TI - [The human lens' transparence changes in children, adolescents, and young adults
with diabetes mellitus type I].
AB - Authors followed up the changes' development of the human lens' transparence in
213 children and young adult patients with diabetes mellitus type I. As initial
changes of the lens' transparence they considered the posterior "Y" suture
accentuation, because it was noticed in 44.4 % of lenses during the first 10
years of the metabolic disease duration, in contrast to 28.1 % representation of
this dissociation in the control group of patients without diabetes (p = 0.012),
and it was always markedly more often in patients with myopia. Substantial
changes were detected predominantly during the sixth until the tenth year of
duration of the basic disease as fine subcapsular opacities graded as first
degree of lens transparency changes in 48 % of eyes. After 10 years of the
disease duration, the lenses were never clear. Consequently, the changes in the
transparency in the anterior subcapsular layer associated in 18 %. After 15 years
of diabetes duration, we detected opacities in the anterior and posterior
subcapsular layers of the lenses, graded as second degree of lenses transparence
changes in 85 % of eyes. This subjective evaluating of lenses' opacity changes by
means of the slit lamp examination was correlated with densitometric examination
by means of Pentacam camera in a representative sample of 29 patients. In the
first degree of lenses' transparence changes, the posterior subcapsular layer was
affected in 50 %, and in the second degree, the opacities in this layer were
found practically in 90 % of cases. False positive result in clear lenses or
congenital opacities or "Y" suture was not detected. In general, the affected
lens transparency did not basically influence the visual acuity and the decrease
of contrast sensitivity was not statistically significant (p = 0.34). For the
initial change of the lenses' transparency is also determining the patient's age
at the onset of the diabetes mellitus type I. The changes are more common if the
onset of the disease is after the fifteenth year of age as before that (p =
0.026). The authors also detected sporadic opacities in 4.2 % of eyes, probably
of congenital origin (out of them, in two patients there was bilateral finding of
the cerulean cataract) without visual acuity decrease.
PMID- 17039919
TI - [The use of accommodative lenses for surgical correction of the presbyopia using
the Prelex method].
AB - The authors refer about their experience with the surgical correction of the
presbyopia by means of the Prelex (presbyopic lens exchange) method. Patients,
who underwent this type of refractive surgery procedure to decrease their
dependency on glasses correction for far as well as for near vision (12 patients,
23 eyes) and 1 young female patient (2 eyes) with juvenile cataract and high
hyperopia, were included in the study. The average age at the time of the surgery
was 51.0 +/- 5.5 years (range, 19-77 years). The average follow up period of the
whole group of patients is 9.8 months (range, 1-13 months). Depending on the type
of the lens implanted, the group was divided into subgroup A with the
accommodative lens 1 CU produced by Human Optics Company implanted, and subgroup
B with the accommodative lens Kellan TetraFlex KH 3500 produced by LensTec
Company implanted. The subgroup A consists of 8 patients (15 eyes) with the
average preoperative refractive error +2.35 +/- 3.45 diopters. The average
uncorrected visual acuity of this group was 0.24 +/- 0.18, and the average best
corrected visual acuity was 0.77 +/- 0.22 at the time before the surgery. The
average glasses correction for near was +4.1 dioptres, and the uncorrected vision
for near was Jaeger's table Nr. (J) 13. The B subgroup consists of 5 patients (10
eyes). The average preoperative refractive error was +2.23 +/- 0.93 diopters. The
average value of the uncorrected visual acuity before the surgery was 0.43 +/-
0.28, and the average corrected visual acuity was 0.82 +/- 0.25. The average
value of the glasses correction for near was +5.25 and uncorrected vision for
near J 13. The final average postoperative error at the time of the last visit
was in the A subgroup +0.06 +/- 1.17 dioptres. The average uncorrected visual
acuity was 0.69 +/- 0.24, and the average best-corrected visual acuity 0.96 +/-
0.12. The average vision of the patients of this subgroup for near was J 3. In
the B subgroup we found at the last visit the average final value of the
postoperative refractive error -0.2 +/- 0.72 dioptres. The average uncorrected
visual acuity 0.57 +/- 0.22 and the average corrected visual acuity 0.95 +/-
0.12. Average uncorrected vision for near was J 5. We did not notice any serious
per- or postoperative complication of this procedure.
PMID- 17039920
TI - [The quality of vision in premature infants--first results].
AB - In last years, thanks to the development in neonatology, the numbers of saved
premature children with high co-morbidity are rapidly growing. Contrary to great
advances in contemporary neonatology, the saved premature children are not spared
different health's problems in the future life, including the vision. The main
cause remains the retinopathy of prematurity and neurological diseases. In the
study the authors present first results of their examinations of visual functions
in premature children at the school age comparing with the group of healthy,
mature children of the same age.
PMID- 17039921
TI - [The color Doppler ultrasonography in glaucoma diagnosis].
AB - The insufficiency of the autoregulation at the optic nerve's head may cause the
glaucoma optic neuropathy (GON). If the long-term stressing exists and an
additional endurance arises, the autoregulation may fail and significant changes
of the resistance index (RI) at the central retinal artery (CRA) and at the
posterior ciliar artery (PCA) can be detected by color flow ultrasonography.
Resistivity index represents peripheral resistance. It is displayed in numerical
value 0-1. 0 indicates none peripheral resistance, 1 indicates maximal peripheral
resistance. The goal of this paper was to determine a risk value of the RI at the
CRA and PCA that could suggest possible damaging of the optic nerve. Two groups
of the patients were evaluated in the course of 4 years duration of the study. In
the I. Group were 72 patients (144 eyes) with GON and with intraocular pressure
(IOP) 14-24 mm Hg. The II. Group consisted of 25 healthy men (48 eyes) without
diagnosis of GON and with IOP values 14-20 mm Hg. There were RI measurements at
all patients at the CRA and CPA at the idle mode and immediately after ordinary
addition endurance (performing squatting--Master test). The statistical analysis
by T test was evaluated with value: 0.05. CONCLUSION: According to our findings,
the difference between RI: 0.12 +/- 0.03 at the CRA at the idle mode and
immediately after ordinary addition endurance is significant for damaging of the
autoregulation at the optic nerve's head. For assessment of the insufficiency of
the autoregulation at the optic nerve's head RI from PCA is not significant.
PMID- 17039922
TI - [The influence of corneal thickness on level of intraocular pressure in the group
of healthy persons and patients with primary open angle glaucoma (POAG)].
AB - AIM: To asses the relation between the level of intraocular pressure (IOP) and
central corneal thickness (CCT), and to examine the dependence of CCT on age, sex
and refraction in the control group of healthy persons (CG) and the group of
patients with POAG. METHODS: The control group was formed by 42 eyes of healthy
people and 20 eyes of patients with POAG. There were 26 women and 16 men in CG
with a median age of 27.5 years and a median refraction of 0 D. The study group
with POAG included 9 women and 11 men, with a median age of 71 years and median
refraction of 0 D. The corneal thickness was measured with an ultrasonic
pachymeter and the IOP with an applanation tonometer. RESULTS: A mean IOP level
in CG was 15,4 +/- 5,6 mm Hg and a mean CCT level 558 +/- 42 microm. In the study
group of POAG there was a mean IOP level 19,6 +/- 4,6 mm Hg, and a mean CCT level
562.7 +/- 35.7 microm. In the CG a significant positive correlation was found
between CCT and IOP (p = 0.01). The dependence of CCT on sex (p = 0.92),
refraction (p = 0.99) and age (p = 0.41) was not statistically significant. On
the contrary, in the study group of POAG no significant correlation between CCT
level and IOP level was found (p = 0.15). The dependence of CCT level on sex (p =
0.43), refraction (p = -0.08) and age (p = -0.17) was also not statistically
significant. The difference in the CCT level between CG and the study group of
POAG was not significant (p = 0.81). The IOP level appeared to be the only
significant difference between both groups (p = 0.007). CONCLUSION: The level of
IOP was influenced by CCT only in the control group of healthy persons. This
dependence was not significant in the group of persons with POAG.
PMID- 17039923
TI - [Ocular symptoms as an indication for carotid endarterectomy].
AB - Ocular symptoms can be the first sign of carotid artery stenosis. In our carotid
endarterectomy patients group were ocular symptoms present in 15%, as the only
sign (without accompanying neurological signs) in 10.5%. Amaurosis fugax was a
dominant sign in 56 cases, blindness in 5, quadrantanopia in 3; trochlear and
oculomotor nerve paresis in one case. Angiography finding of more than 60% ICA
stenosis according NASCET criteria was an indication for surgery. The operative
technique per se was a microsurgical endarterectomy with selective peroperative
shunt application. The 30-d morbidity was 3%--with one case of central retinal
artery embolization and subsequent blindness and another case of major residual
neurological deficit due to hyperperfusion syndrome and the resultant capsular
hemorrhage. Shunt was applied in 3% of cases and microscope was used always since
the beginning of the dissection up to the final suture. Considering low
perioperative morbidity/mortality rates the carotid endarterectomy represents an
important means of brain ischaemia profylaxis. In the process of hemodynamically
significant ICA stenosis, indication for surgical management the authors
emphasize the role of ocular signs and symptoms and thus the importance of an
ophthalmology consultant.
PMID- 17039924
TI - [How severe eye injuries were treated more than 50 years ago].
PMID- 17039925
TI - [Research on the progress of neuroprosthesis for the limb motor system].
AB - This paper reviews the current developing situation of neuroprostheses which are
based on the functional electrical stimulation (FES) technique and are used to
provide limb movements. It also discusses the major challenges of
neuroprostheses, which will be faced in the future development and in the
clinical applications for the rehabilitation of spinal cord injury and stroke.
PMID- 17039926
TI - [A study on the interpolation algorithm for the serial-parallel robot-controlled
HIFU].
AB - According to the hardware characters of the high intensive focused ultrasound
(HIFU) serial-parallel robots, this paper presents an algorithm of 2-grade
interpolation scheme which includes the rough and fine interpolations. Both pre
acceleration and post-acceleration are employed to meet the restrictive
requirements of coordinated dynamic performance and the detailed procedure of the
interpolation algorithm is given too.
PMID- 17039927
TI - [An image acquisition & processing system of the wireless endoscope based on
DSP].
AB - This paper covers an image acquisition & processing system of the capsule-style
endoscope. Images sent by the endoscope are compressed and encoded with the
digital signal processor (DSP) saving data in HD into PC for analyzing and
processing in the image browser workstation.
PMID- 17039928
TI - [The database and its data sharing of neuropathic images].
AB - This paper introduces the basic principle and method of establishing a database
for neuropathic images, and discusses its significance and data sharing. The
database is composed of three data volumes about basic knowledge for images,
cranial sectional anatomy and neuropathic images. The data sharing is achieved by
using a method of linking the dynamic network of neuropathic images with database
of neuropathic images. There are three searching approaches: catalog searching,
key words searching and code searching.
PMID- 17039929
TI - [Construction of a regional information system based on standardization and
middleware platform].
AB - In this article, based on the analysis on the regional information system's
development background and its applications, the construction of the regional
medical information system through creating the electronic medical record and the
medicine image data centers is proposed, for information resource sharing. And
then, the system's software construction and various subsystems functions are
mainly introduced. Standardization and the middleware platform are suggested as
the effective way of constructing these two data centers in the present situation
in our country.
PMID- 17039930
TI - [Monitoring the depth of anesthesia using a fuzzy neural network based on EEG].
AB - In this paper, a fuzzy neural network (FNN) is proposed for fusing the anesthesia
information, and realizing the monitoring of the depth of anesthesia (DOA). EEG
data from 31 patients undergoing general anesthesia with different anesthetic
agents, and Kc complexity (Kc), approximate entropy (ApEn) were extracted and the
fuzzy neural network was trained by 25 samples, and tested by the other 6
samples. The results show that the outputs of the fuzzy neural network whose
inputs were Kc and ApEn obtained under the awake state and asleep state, exist
obvious difference. It can be regarded as an quantitative index to estimate DOA.
PMID- 17039931
TI - [The application of data mining technology in the hospital management].
AB - This paper introduces the application and role of data mining technology in the
hospital management.
PMID- 17039932
TI - [An introduction of the principle for the middleware based on HL7].
AB - This article introduces the development of a middleware based on HL7, which
solves the problem of data integration and sharing effectively and successfully,
among the hospital internal subsystems and different hospitals' information
systems.
PMID- 17039933
TI - [Research and implementation of the registry system of multimedia EMR sharing
based on XDS-I].
AB - Referring to XDS-I and RIM of ebXML, we have built a registry system for
electronic medical records sharing which is introduced, in this paper.
PMID- 17039935
TI - [Non-linear registration of MR brain images integrated with machine learning].
AB - This paper presents a machine learning method to select best geometric features
for deformable brain registration for each brain location. By incorporating those
learned best attribute vector into the framework of HAMMER registration
algorithm, The accuracy has increased by about 10% in estimating the simulated
deformation fields. At the same time, on real MR brain images, we have found a
great deal of improvement of registration in cortical regions.
PMID- 17039934
TI - [Segmenting lung fields in serial chest radiographs using both population and
patient-specific shape statistics].
AB - This paper presents a new deformable model using both population-based and
patient-specific shape statistics to segment lung fields from serial chest
radiographs. First, a modified scale-invariant feature transform (SIFT) local
descriptor is used to characterize the image features in the vicinity of each
pixel, so that the deformable model deforms in a way that seeks for the region
with similar SIFT local descriptors; second, the deformable model is constrained
by both population-based and patient-specific shape statistics. At first,
population-based shape statistics plays an leading role when the number of serial
images is small, and gradually, patient-specific shape statistics plays a more
and more important role after a sufficient number of segmentation results on the
same patient have been obtained. The proposed deformable model can adapt to the
shape variability of different patients, and obtain more robust and accurate
segmentation results.
PMID- 17039936
TI - [The study of associated reconstruction using MV linear accelerator and cone-beam
CT].
AB - In this paper, we proposed a new scan mode and image reconstruction method, which
combines the data from both the linear accelerator and the cone-beam CT to
reconstruct the volume with a limited rotation angle and low sampling rate. The
classical filtered backprojection method and the iterative method are utilized to
reconstruct the volume. The reconstruction results of the two methods are
compared with each other with a relavant anlysis given here.
PMID- 17039937
TI - [Exploration for building PACS and RIS].
AB - This article elaborates key points of the PACS and RIS project: its overall
planning, implementation step by step, integration of PACS and HIS based on IHE,
and the prudent selection of partners and so on.
PMID- 17039938
TI - [Development of DICOM software platfrom for medical image communication].
AB - In this paper, we have brought forward the framework design of DICOM software
platform, using the SUR-DICOM-Lib software and have completed the connection test
with the RSNA-CTNT Test Node. PACS, DICOM, realize
PMID- 17039939
TI - [Research on testing the robustness of DICOM-e-mail secure teleradiology
systems].
AB - DICOM-e-mail is a secure teleradiology protocol released by German Radiology
Society and has already been applied clinically. To improve the robustness of the
system, the protocol has been upgraded by adding some mechanisms such as system
feedback. Moreover, a test method is also implemented by sending erroneous mails
to application software that supports DICOM-e-mail. Through the tests for two
different DICOM-e-mail teleradiology application, the validity of the new
protocol is proved and at the same time some bugs are found. The implementation
of the latest protocol and the general error tests can help to make the whole
teleradiology system a better robustness. The implementation of DICOM-e-mail
protocol in our country is also discussed in this paper.
PMID- 17039940
TI - [A 3-D image reconstruction algorithm based on helical CT raw data].
AB - A CT 3-D image is reconstructed based on a lot of 2-D slice images. A new 3-D
image reconstruction method, presented in this paper, is to use the helical scan
continuity, sufficient condition of image reconstruction and the raw data from a
few helical scan cycles to reconstruct,by a direct interpolation algorithm, 2-D
images and then 3-D images.
PMID- 17039941
TI - [Research on the distributed PACS based on grid technology].
AB - In this paper, we introduce the grid technology into the design of the
distributed PACS. First, we analyse the architecture and functions of OGSA-DAI,
and then, introduce a model of the distributed PACS based on OGSA-DAI, and give a
detailed analysis on its basic components and workflow. Finally, we make a
conclusion on the distributed PACS based on grid technology.
PMID- 17039942
TI - [The application value of the PACS in general hospitals].
AB - In order to evaluate the diagnostic value of the PACS, the PACS has been applied
to Dept.of Radiology in Renji Hospital in Shanghai for nearly two and a half
years. Clinical practice shows that the doctors can work more efficiently and
accurately by using the diagnostic workstation of PACS. PACS is an inevitable
development trend of image diagnosis and is playing a more and more important
role in clinical applications.
PMID- 17039943
TI - [Study on network architecture of a tele-medical information sharing platform].
AB - In the article,a plan of network construction which satisfies the demand of
applications for a telemedical information sharing platform is proposed. We
choice network access plans in view of user actual situation, through the
analysis of the service demand and many kinds of network access technologies.
Hospital servers that locate in LAN link sharing platform with node servers,
should separate from the broadband network of sharing platform in order to ensure
the security of the internal hospital network and the administration management.
We use the VPN technology to realize the safe transmission of information in the
platform network. Preliminary experiments have proved the plan is practicable.
PMID- 17039944
TI - [Design and implementation of a medical record management subsystem as a part of
a telemedical system].
AB - This paper introduces the work on the design and implementation of a medical
record management subsystem, which is a part of a telemedicine system based on
Microsoft .NET. First, an analysis is given on components and structure of
medical record, together with an explanation for what is needed in a
teleconsultation, how they should be organized and realized in a database, and
how to deal with consultation data granularity using XML in combination with
database; second, the work done during the realization stage is expatiated,
including system analysis and design, database design, and system implementation.
PMID- 17039945
TI - [JPIP-based wireless transmission and display of high resolution DICOM medical
images].
AB - This paper uses JPIP protocol to transmit and display high-resolution medical
images through the wireless network. JPIP server extracts medical images from
PACS system, transforms the format of medical images, and parses and recomposes
the JPEG2000 codestream. Wireless PDA access and display DICOM medical images
through accessing the JPIP server.
PMID- 17039946
TI - [The registration of false teeth and the others].
AB - The quality control of false teeth should include the control for designing and
processing. The registration of false teeth should emphasize particularly on the
qualification of the makers, technology management, quality control and the
labeling.
PMID- 17039947
TI - [An investigation of medical devices in use in hospitals in Shanghai Baoshan
District].
AB - This article briefly presents the situation of medical devices in use in
hospitals in Baoshan District, including purchasing, daily management, routine
maintaining and the usage, and mainly puts forward some existent problems, such
as less attention to maintenance, irregular operations, nonstandard measurements
and calibrations, and shortage of relative files. In the end of this article,
some suggestions are made, for example, to set up a "cooperation team for
maintenance
PMID- 17039948
TI - [Automatical updating the application software on the hospital information
system's client].
AB - In view of the current predicament of updating the application software on the
hospital information system's client, the Synchronizer module in PowerBuilder is
used in combination with some techniques of the windows operation system, in
order to implement automatic synchronistic updating of the application software
on the Hospital Information System's client before the program's running.
PMID- 17039949
TI - Material surfaces and MRSA.
AB - It appears that our hospitals are facing serious threats from antibiotic
resistant bacteria, especially meticillin-resistant Staphylococcus aureus (MRSA).
In this article, some of the new materials related solutions to these threats are
discussed
PMID- 17039950
TI - Next generation polymer nanocomposites.
AB - Developments in nanocomposite technology are giving designers a much broader set
of combinations of materials and properties to use. This will lead to medical
devices with mechanical properties and enhanced integration of different
functions. Some of the possibilities are described here.
PMID- 17039951
TI - Bonding cyanoacrylates and ultraviolet-curing adhesives.
AB - This guide to the correct adhesives to use for bonding medical plastics reviews
recent technological advances and the benefits they offer. Material and design
considerations are also examined.
PMID- 17039952
TI - Metal injection moulding for medical devices.
AB - One moulding process is described here that offers speed and cost savings
together with precision and robust material properties. New product designers are
advised to design for it from the outset.
PMID- 17039953
TI - Strategic planning for U.S. premarket approval submissions.
AB - The United States premarket approval (PMA) process is costly and time-consuming
and differs in important ways from the CE-marking process. This article discusses
the importance of strategic planning for submission of a PMA and the issues that
should be considered, which can lead to a reduction in the time and cost
involved.
PMID- 17039954
TI - Wireless pressure monitoring systems.
AB - Sensor systems based on micro- and nanotechnologies allow continuous monitoring
and control of therapeutic procedures. Advances in this area are transferring
this functionality into long-term, fully implanted systems. Some of these
developments and applications are described here.
PMID- 17039955
TI - Thin-client medical devices.
AB - Designing as little functionality as possible on the device, and placing the
processing burden on the server, can reduce the cost of medical devices and
provide other benefits.
PMID- 17039956
TI - Using ultrasonic technology to manufacture products.
AB - The use of ultrasonics in medical device manufacturing is gaining momentum as
designers and engineers take advantage of the benefits it offers. A number of
example medical applications are described that demonstrate the utility of
ultrasonic processing in their manufacturer.
PMID- 17039957
TI - Biosensing in California.
AB - Worldwide sales of medical biosensors now exceed pounds 2.8 billion (Euro 4.1
billion) per annum and applications of biosensing technology are highly relevant
to United States homeland security. A recent mission funded by the United Kingdom
government to California, USA, investigated some of the development work going on
there.
PMID- 17039958
TI - Achieving effective component placement.
AB - Greater use of electronics assemblies, a decrease in product size and increased
complexity are placing new demands on placement systems.
PMID- 17039959
TI - The medical device industry in Italy.
AB - Important changes have been taking place in Italy, particularly in the areas of
enforcement of the medical device Directives and reimbursement. An update on
these developments and news on the industry in Italy are provided here.
PMID- 17039960
TI - Meeting the challenges in Italy.
AB - Companies in the dynamic biomedical district of Mirandola are finding success in
the new strategies they are adopting. This article reviews their challenges and
initiatives.
PMID- 17039961
TI - Implantable PEEK extends the options.
AB - The availability of a performance polymer alongside the established metals and
ceramics for orthopaedic applications offers more choice and capabilities.
PMID- 17039962
TI - Giving patients the choice of home therapy.
PMID- 17039963
TI - Setting quality measures for dialysis in SNFs.
PMID- 17039964
TI - Dialysis Facility Compare: A consumer choice tool gets better.
PMID- 17039965
TI - Making things work (successfully) in hospital-based dialysis.
PMID- 17039966
TI - Understanding software license and services agreements.
PMID- 17039967
TI - Use of the NxStage system one for daily home hemodialysis.
PMID- 17039968
TI - Dialysis: A love/hate relationship? Interview by Courtney Stuempges.
PMID- 17039969
TI - The Northwest Kidney Centers' experience with the Aksys PHD system.
PMID- 17039970
TI - Dialyzing at home with the 2008K.
PMID- 17039971
TI - Document it!
PMID- 17039972
TI - Lessons learned--one facility's experience with venturing into the home
hemodialysis market.
AB - The home hemodialysis program team at Community/ Physicians Dialysis Center
Fairborn began training their first patient in October 2004. They now have six
home patients dialyzing using either daily nocturnal or short daily home
hemodialysis. Improved patient outcomes, including excellent morbidity/mortality
figures, are hallmarks of the success of the. program. In addition, all home
patients have seen moderate to large improvements in quality of life since
starting to dialyze at home. This article describes the details involved with
developing the program, and what was learned along the way. It is the hope of
this author that others will be encouraged by this story, and embrace the
challenge of providing this exciting modality option to the patients they serve.
PMID- 17039974
TI - Clinical semiology of neuromuscular diseases (2).
PMID- 17039973
TI - Why we need the option of more dialysis.
PMID- 17039975
TI - Readthrough strategies for stop codons in Duchenne muscular dystrophy.
AB - Duchenne muscular dystrophy is due to mutations of the dystrophin gene. These are
large deletions or duplications in 80% of cases, while premature stop codons
(nonsense point mutations) account for 7% of cases. This subgroup of patients may
take advantage of the properties of the antibiotic gentamicin to suppress stop
codons (readthrough). The efficiency of the readthrough varies inversely to the
efficiency of a stop codon and is also affected by the different components of
the drug. Following gentamicin treatment of mdx mice, dystrophin was re-expressed
up to 20% of normal level, albeit with variability among animals. Human trials
with gentamicin have so far obtained doubtful results. PTC124 belongs to a new
class of small molecules that mimics at lower concentrations the readthrough
activity of gentamicin. The administration of PTC124 resulted in the production
of full-length and functionally active dystrophin both in vitro and in mdx mice.
A Phase II clinical trial is now in course and will be terminated at the end of
2006.
PMID- 17039976
TI - Parkin and its association with alpha-synuclein and AbetaPP in inclusion-body
myositis and AbetaPP-overexpressing cultured human muscle fibers.
AB - Parkin, an E3-ubiquitin ligase in the ubiquitin-proteasome system, facilitates
degradation of alpha-synuclein and other proteins. Since ubiquitinated
multiprotein-aggregates containing amyloid-beta (Abeta), alpha-synuclein, and
other proteins, are characteristic of sporadic inclusion-body myositis (s-IBM)
muscle fibers, we asked whether parkin might have a role in s-IBM pathogenesis.
We studied the association of parkin with alpha-synuclein and Abeta-precursor
protein (AbetaPP) in s-IBM muscle biopsies and in our IBM model based on
overexpression of AbetaPP into cultured human muscle fibers. We report the
following in s-IBM muscle fibers: a) parkin was increased 2.7 fold and
accumulated in aggregates also containing Abeta and alpha-synuclein; b) alpha
synuclein was increased 6.3 fold; c) parkin physically associated with alpha
synuclein and AbetaPP; d) alpha-synuclein and AbetaPP were ubiquitinated. In the
IBM model: a) parkin was increased 2.7 fold, b) it associated with alpha
synuclein and AbetaPP. CONCLUSION: 1. This is the first demonstration that in a
human muscle disease alpha-synuclein associates with parkin, and might be
ubiquitinated by it. 2. The small increase of parkin relative to the much larger
increase of alpha-synuclein might be insufficient to secure complete
ubiquitination and consequent degradation of alpha-syn. 3. AbetaPP might be a
novel substrate of parkin.
PMID- 17039977
TI - Italian guidelines for molecular analysis in myotonic dystrophies.
AB - Myotonic dystrophies, the most common form of adult muscular dystrophy, comprise
at least two forms, clinically and genetically heterogeneous. Myotonic dystrophy
type 1 and type 2 are both caused by unstable repetitions in untranslated gene
regions: a [CTG]n expansion in the 3' region of the DMPK gene on chromosome 19q13
(DM1) and [CCTG]n tetranucleotide repeat located in the first intron of the ZNF9
gene on chromosome 3q21 (DM2). DM clinical features are caused by a gain of
functions RNA mechanism in which the CUG and CCUG repeats alter nuclear
functions, including alternative splicing of shared genes. Southern blot and/or
polymerase chain reaction PCR-based approaches allow the detection of DM
mutations in almost 100% of cases, however, the expansion size and the elevated
grade of somatic instability make molecular testing for DM a diagnostic
challenge. The increased use of DNA testing for DM generates many questions
regarding the indications and interpretations of the test which require
standardized methods, routinely available in molecular genetic laboratories.
Here, we propose Guidelines for the molecular diagnosis of DM1 and DM2 approved
by the Italian Ministry of Health in 2005 (Piano Nazionale Linee Guida, PNLG).
Best practice for DM molecular analysis in diagnostic application, presymptomatic
and prenatal testing, using direct and indirect approaches are described, with
particular attention focused on ethical, legal and social issues. Overviews of
materials used in the molecular diagnosis, as well as internet resources, are
also included.
PMID- 17039978
TI - Early onset Charcot-Marie-Tooth disease caused by a homozygous Leu239Phe mutation
in the GDAP1 gene.
AB - Mutations in the ganglioside -induced differentiation-associated protein 1
(GDAP1) gene are common a cause of the Charcot-Marie-Tooth (CMT4A) disease with
autosomal recessive mode of inheritance. To date more than twenty mutations in
the GDAP1 gene have been reported in patients suffering from the demyelinating,
axonal or mixed form of Charcot-Marie-Tooth disease. Only in a few CMT4A affected
patients sural nerve biopsy findings have been provided. We report a homozygous
Leu239Phe mutation in the GDAP1 gene in a 39-year-old female with a severe form
of mixed axonal and demyelinating Charcot-Marie-Tooth disease.
PMID- 17039979
TI - Tumor-like brain lesions in a patient with Hashimoto encephalopathy and
hereditary motor and sensory neuropathy.
PMID- 17039980
TI - Exon skipping with U7 gene transfer.
PMID- 17039981
TI - Predictors of death within six months in patients with advanced AIDS.
AB - OBJECTIVES: This study sought to identify potential predictive variables of death
within 6 months in patients with advanced AIDS. METHODS: Investigators enrolled a
consecutive series of patients with advanced AIDS admitted to a skilled nursing
facility in New York City over a 1-year period. Demographic, clinical,
laboratory, and outcome data were abstracted from medical records using a
standardized data collection instrument. RESULTS: Of the 152 patients enrolled
during the study period, 61 patients (40%) died within 6 months from date of
admission. Serum albumin, percent deviation from ideal body weight, and number of
comorbidities at the time of admission proved to be the best combination of
predictors of death within 6 months. SIGNIFICANCE OF RESULTS: The decrease in
AIDS mortality over the past decade, along with an increase in prevalence due to
longer survival, has been attributed primarily to the successful use of highly
active antiretroviral therapy (HAART). HAART regimens, however, can also produce
both short-term adverse effects and long-term complications. The prognostic model
developed by this study may be useful in guiding treatment decisions in patients
with advanced AIDS for whom a more palliative care plan may be sought.
PMID- 17039982
TI - A pilot examination of the impact of cancer patients' fatigue on their spousal
caregivers.
AB - OBJECTIVE: In this pilot project we examined the quality of life of spouses of
cancer patients who had significant fatigue. METHODS: We assessed both the
spouses of cancer patients and the patients who presented with chemotherapy
induced fatigue and anemia. Study endpoints included the impact that cancer
patients' fatigue had on their spouses' quality of life, including their own
levels of fatigue, depressive symptoms, activity levels, work absenteeism, and
marital adjustment. We examined the extent to which changes in patients' fatigue
from baseline to one month follow-up were associated with changes in spouses'
quality of life indices. RESULTS: 25 couples completed the study. Seven (28%)
spousal caregivers reported handling fewer responsibilities at work, 8 (32%) had
reduced their work hours, and 8 (32%) felt that they were less effective overall
at work. Spousal caregivers also missed a significant amount of time at work
during the month long study, missing an average of 2.7 (SD = 2.95) days, with an
additional 1.29 (SD = 2.97) sick days and 1.76 (SD = 2.63) vacation days during
that time. Spouses reporting greater levels of caregiver strain were more likely
to have increased fatigue at baseline (F1,23 = 8.11, p < .01), and worse dyadic
adjustment at both time points (baseline: F1,23 = 7.80, p < .01; follow-up: F1,21
= 9.24, p < .01). Also, those with more caregiver strain were less likely to
engage in social activity at baseline (F1,23 = 6.11, p < .05) and more likely to
engage in less work by the one month follow-up (F1,20 = 8.36, p < .01).
SIGNIFICANCE OF RESULTS: Spouses who were identified as having elevated burden
experienced more personal fatigue, had worse dyadic adjustment, reported poor
energy levels, and tended to engage in fewer work and social activities; the
impact of patient's fatigue level on these parameters was highly variable in this
small pilot study.
PMID- 17039983
TI - Are palliative cancer patients willing and able to participate in a physical
exercise program?
AB - OBJECTIVE: The primary aim of the present article was to identify palliative care
patient populations who are willing to participate in and able to complete a
group exercise/physical training program designed specifically for the individual
patient. METHOD: We conducted a prospective phase II intervention study examining
the willingness and ability of palliative care cancer patients to participate in
a group exercise physical training program. Patients who were diagnosed with
incurable cancer and had a life expectancy of less than 1 year at two outpatient
clinics were invited to participate in an exercise program in the hospitals. The
groups met twice a week over a 6-week period. RESULTS: One hundred one
consecutive patients were asked for inclusion. Sixty-three patients agreed to
participate. Sixteen (25%) of the 63 patients dropped out after consent was
given, but before the program started due to medical problems, social reasons, or
death. Thus, 47 patients started the exercise program. Thirteen patients withdrew
during the program due to sudden death, medical problems, or social reasons. The
most frequent reasons for withdrawal were increased pain or other symptoms.
Thirty-four patients completed the exercise program. SIGNIFICANCE OF RESULTS: A
high proportion of incurable cancer patients were willing to participate (63%) in
a structured exercise program. The attrition rate was high, but despite being
severely ill, 54% of the patients completed the exercise period. This shows that
a physical exercise program tailored to the individual patient is feasible in
this population.
PMID- 17039984
TI - Patient desires: a model for assessment of patient preferences for care of severe
or terminal illness.
AB - OBJECTIVE: Patient-centered care is better achieved through a comprehensive
understanding of patients' preferences for how they want to live their life and
how they want to influence their own death. Though much has been written on
identifying goals of care, it is often difficult for clinicians to articulate
patient goals to guide care planning. We explored the literature on patient's
preferences for their care in chronic or life-limiting illness to develop a model
for assessment of patient perspectives. We then illustrated our model with
composite patients from our clinics and we provide questions to guide patient
discussion. METHODS: We searched MEDLINE from 1986 to 2004 for primary research
articles that relate primarily to a patient's preferences for his or her care. We
reviewed over 3500 titles, abstracts, and research papers. Hundreds of articles
described patients' quality of life, health status, or satisfaction. We excluded
consensus guidelines, non-English papers, reviews, and articles focused on
medical professional perspectives. Forty-eight studies focused primarily on
patient preferences. Using an iterative process, we identified unique issues and
broader themes in patients' desires for their care. RESULTS: Studies focused on
patients with cancer, those in hospice or those with terminal disease. Three
domains emerged: patient feelings about disease, feelings about suffering, and
feelings about the circumstances of death. Attention was given to the differences
between patients in terms of the strength and persistence of feelings in each
domain. SIGNIFICANCE OF RESULTS: Based on existing data, there are three
fundamental domains of patient perspective that influence preferences for care.
These domains can be assessed by the care team to guide the development of a plan
of care and to identify areas of conflict. Our review identifies gaps in the end
of-life literature and areas for future work in patient preferences.
PMID- 17039985
TI - Pain management and related factors in advanced cancer patients who initiated
opioid therapy in an outpatient setting.
AB - OBJECTIVE: The aim of this study was to clarify the state of pain management in
Japanese patients with advanced cancer who initiated opioid therapy in an
outpatient setting. METHODS: Interview surveys using questionnaires were
conducted and medical records were reviewed. Pain relief was defined as >33%
decrease in worst pain intensity score, and significance of early pain relief was
investigated in terms of changing self-efficacy for activities of daily living
(ADL). Factors related to early pain relief were also investigated. RESULTS: The
study was conducted between June and December 2003, on 20 patients (13 women, 7
men; mean age, 59 years). Compared to score at initiation of opioid
administration (Numerical Rating Scale, 8.3 +/- 1.3), pain relief was generally
insufficient at 2 weeks (early pain relief ratio was only 42%). Patients with
sufficient pain relief at 2 weeks displayed significant improvements in numerous
ADL functions and symptom-coping efficacy (p = 0.037), confirming the importance
of early pain relief. Early pain relief was associated with high frequency of
hospital visits before opioid administration and absence of sudden excavation
within the first 2 weeks. SIGNIFICANCE OF RESULTS: Result of this study indicated
insufficient pain relief at an outpatients setting with advanced cancer patients.
In the meantime, patients had who their pain decrease after 2 weeks also had
improved ADL and self-efficacy at the same time. These findings suggest that to
achieve early pain relief in an outpatient setting, clinical staff must assess
pain earlier and inform patients of possible breakthrough pain following opioid
administration and available treatments for such occurrences.
PMID- 17039986
TI - Methadone in the treatment of pain and terminal delirum in advanced cancer
patients.
AB - OBJECTIVE: This prospective study documents the use of methadone as part of an
opioid rotation strategy in patients with uncontrolled pain and severe delirium
admitted for terminal care to a tertiary cancer palliative care hospital.
METHODS: We reviewed the treatment of 20 patients with severe pain and delirium
at the end of life who's delirium did not improve 24 h or longer after starting a
neuroleptic medication. RESULTS: Ten male and 10 female patients, 47 to 77 years
old, were rotated or "switched" to methadone due to uncontrolled pain in the
setting of delirium, limiting further opioid dose escalation. At 2 weeks, a total
of 10 patients had expired. Of the 10 patients who were alive 2 weeks after
starting methadone, 7 patients were stable on an average of 1.1 mg/h methadone, 2
patients were restarted on morphine IV and one on Percocet. The calculated
average equianalgesic dose of methadone was 9% (2%-17%) of the previous morphine
equivalent dose. Of the 20 patients who were switched to methadone for what
appeared to be terminal delirium, the pain control was significant in 15,
moderate in 3, and unchanged in 2 patients. Average analgesia was good to
excellent (average Numeric Analog Scale rating [NAS] decreased from 8.2 to 2.5).
Sedation had decreased from 1.65 to 0.55 on a scale of 0 to 3. Of the 20
patients, improvement of cognitive status was significant in 9, moderate in 6,
partial in 2, and none in 3 patients. The Memorial Delirium Assessment Scale
(MDAS) showed improvement from an average of 23.6 prior to the switch to 10.6 3
days after. Decreased alertness on methadone was devoid of agitated features.
SIGNIFICANCE OF RESULTS: Our study suggests that methadone can be effective in
the treatment of both refractory pain and what appears to be terminal delirium.
Most patients in our group had at least a short-term improvement in mental status
as well as significant and lasting improvement in analgesia.
PMID- 17039987
TI - Clinical assessment of depression in terminally ill cancer patients: a practical
guide.
AB - Depression is commonly experienced by cancer patients at the end of life. The
identification of patients suffering from depression is essential to provide
clinicians with an opportunity to relieve considerable suffering. However, the
assessment of depressive symptoms is complex and often challenging in a
terminally ill cancer population. This article offers practical guidelines to
assist clinicians with the diagnosis of depression, reviews the defining symptoms
of depression and their unique presentation in patients at the end of life,
suggests modifications of the standard diagnostic interview, and provides
examples of specific assessment questions to target depressive symptoms at the
end of life.
PMID- 17039988
TI - Caring for those who care for the dying: coping with the demands on palliative
care workers.
AB - The article reviews the complex and demanding field of palliative care, noting
the sources of the stresses and strains that the health care workers often
encounter. It illustrates the multidimensional needs of patients, the reasons why
they and/or their families may hamper palliative care, and, mostly, what can be
done to deal with and-better yet-prevent palliative workers' burnout.
PMID- 17039989
TI - Development of Wernicke encephalopathy in a terminally ill cancer patient
consuming an adequate diet: a case report and review of the literature.
AB - Malignancy-associated primary thiamine deficiency has been documented in several
experimental tumors, clinical case reports, and in patients with fast growing
malignancies. We report a terminally ill cancer patient who developed delirium.
Close examination of the patient demonstrated that delirium was caused by
thiamine deficiency, although she had been consuming an average of 990 cal/day
for the past 3 weeks. Malabsorption or consumption by the tumor was considered
the mechanism of thiamine deficiency. Early recognition and subsequent treatment
resulted in successful palliation of delirium. In terminally ill cancer patients,
clinicians must remain aware of the possibility of Wernicke's encephalopathy,
when the patients develop unexplained delirium, even if the patient has been
consuming adequate amounts of food. Early intervention may correct the symptoms
and prevent irreversible brain damage, and the quality of life for the patient
may improve.
PMID- 17039990
TI - Wernicke encephalopathy presented in the form of postoperative delirium in a
patient with hepatocellular carcinoma and liver cirrhosis: a case report and
review of the literature.
AB - OBJECTIVE: Although Wernicke encephalopathy has been reported in the oncological
literature, it has not previously been reported in postoperative cancer patients.
METHODS: In this communication, we report a patient of hepatocellular carcinoma
with liver cirrhosis who developed Wernicke encephalopathy in the form of
postoperative delirium. Preoperatively, the patient had a very good appetite and
had eaten all the food of an 1800 cal/day diet until 1 day before operation. The
operation was done without any complications. The patient developed delirium 2
days after the lobectomy of the liver. The level of delirium remained unchanged
until administration of thiamine starting on day 7 postoperatively, which
resulted in palliation of delirium without brain damage. Laboratory data
demonstrated that the serum thiamine level at day 6 postoperatively was below the
lower limit of normal. As the mechanism of Wernicke encephalopathy, we thought
that decreased ability to store thiamine due to liver cirrhosis led to depletion
of thiamine faster than had been expected. RESULTS AND SIGNIFICANCE OF THE
RESEARCH: In cancer patients, clinicians must always remain aware of the
possibility of Wernicke encephalopathy, especially in patients with liver
dysfunction, which decreases the ability to store thiamine in the liver. Early
detection and intervention may alleviate the symptoms of delirium and prevent
irreversible brain damage.
PMID- 17039991
TI - Nursing practice models: time for change.
PMID- 17039992
TI - Sabbatical journey of discovery: recruitment, retention and quality of work life.
PMID- 17039993
TI - Wendy S. Hill.
PMID- 17039994
TI - Health Outcomes for Better Information and Care (HOBIC): integrating patient
outcome information into nursing undergraduate curricula.
AB - Nursing-sensitive outcomes provide common information across sectors, thus
eliminating duplication that frequently occurs as individuals move across
settings. These outcomes also facilitate increased trust among colleagues and
support common understandings of patient care needs, thus enhancing continuity of
care. Outcomes-oriented information is also likely to increase patient safety and
improve overall quality of care. Shared standards and data support consistent
decision-making, as nursing decisions can be tracked back over time to assess
patient care outcomes. Consequently, nurses will have the means to determine the
impact of their interventions on patient outcomes. At the same time, adoption of
common approaches to patient assessment leads to greater professional
accountability and moves nursing care from a task orientation to an outcomes
focus. For administrators, such improvements in monitoring and evaluating patient
outcomes translate into improvements in efficiencies and effectiveness, thus
providing a return on investment in implementing these outcomes within their
agency. For nurses, integration and utilization of outcomes information increases
the visibility and significance of their decision-making and patient care.
Together with patients, nurses can utilize the outcomes information to make
evidence-based decisions and advocate for appropriate care. At an aggregate
level, the use of outcomes information creates a continuous feedback loop that is
essential to ensuring evidence-based care and the best possible patient outcomes,
not only for individuals, but also for families, communities and populations.
Outcomes-oriented care provides a gateway for transforming the way we care for
patients; puts safe, ethical, high-quality care for patients first; embodies the
principles of evidence-based practice; ensures that the value of nursing is
clearly understood within the larger system; and ensures that the requirements
for measurability and accountability can be achieved. This journey is continuous
and is being expanded to engage all other health disciplines in understanding and
documenting their contributions to patient care, both as individual practitioners
and as members of a healthcare team. Preparing nursing students in an outcomes
approach will facilitate systemwide adoption of HOBIC patient outcomes over time
and provide a means to determine the impact of nursing care on our patients.
PMID- 17039995
TI - Case study: on the leading edge of new curricula concepts: systems and safety in
nursing education.
AB - The Nursing Division of the Saskatchewan Institute of Applied Science and
Technology (SIAST) first included systems and patient safety as a priority in its
institutional business and strategic plan in 2003. Three interrelated leading
edge, two-year projects (2004-2006) were launched: Best Practice, Mentorship and
Patient Safety, with the intent that each project would enhance the others. This
case study focuses on the work of the Patient Safety Project Team. The team
developed a project framework and strategic plan, conducted a literature review
and identified key concepts related to systems and patient safety. Strategies to
integrate these concepts into the school's 15 nursing education programs are
being implemented.
PMID- 17039996
TI - Workplace empowerment, work engagement and organizational commitment of new
graduate nurses.
AB - As a large cohort of experienced nurses approaches retirement, it is critical to
examine factors that will promote the engagement and empowerment of the newer
workforce, allowing them to provide high quality patient care. The authors used a
predictive, non-experimental survey design to test a theoretical model in a
sample of new graduate nurses. More specifically, the relationships among
structural empowerment, six areas of work life (conceptualized as antecedents of
work engagement), emotional exhaustion and organizational commitment were
examined. As predicted, structural empowerment had a direct positive effect on
the areas of work life, which in turn had a direct negative effect on emotional
exhaustion. Subsequently, emotional exhaustion had a direct negative effect on
commitment. Implications of these findings for nursing administrators are
discussed.
PMID- 17039997
TI - Nurses' perceptions of medication safety and medication reconciliation practices.
AB - Medication reconciliation (MR) involves the accurate transfer of medication
information across the continuum of care. The aim of this study was to measure
nurses perceptions of patient safety, medication safety and current MR practice
at transition points in a patient's hospital stay. Surveys were distributed to
111 nursing staff in three general medicine units at Capital Health District,
Nova Scotia, in August 2005. A total of 39 nurses (35% response rate) completed
the survey. "Teamwork within units" was the safety culture dimension with the
highest positive response (98.1%), while the processes of handoffs and
transitions received the lowest positive response (42.8%). Key areas identified
for improvement relative to the current level of MR practice include
institutional patient safety systems (e.g., low confidence in existing systems
and procedures), inconsistent practices (e.g., wide variation in whether
community pharmacists are contacted to verify medication profiles), lack of
communication (e.g., between healthcare professionals) and staffing resources
(e.g., MR is perceived as a very time-consuming process). Addressing these
challenges prior to implementing a formalized MR program should help to ensure
success of the project. The insights gained through the use of this survey may
prove valuable to other Canadian healthcare organizations that are implementing
MR services.
PMID- 17039998
TI - Magnet hospital characteristics and northern Canadian nurses' job satisfaction.
AB - Retention of health professionals is a serious problem in northern and rural
Canada. Magnet hospital factors are known to increase job satisfaction, which
contributes to retention. The purpose of this paper is to examine the extent to
which magnet hospital characteristics (management support, nurse-doctor and nurse
manager relationships, professional autonomy and responsibility) contribute to
northwestern Canadian hospital nurses' job satisfaction. Participants were 123
nurses from 13 hospitals in western Canada. They completed a survey and
structured interview that provided data on their attitudes and perspectives about
their hospital jobs. We found that some magnet hospital characteristics apply in
northern and rural western Canadian hospitals. Our findings indicate that
management support and nurse-manager relations are important to nurses' job
satisfaction, but participants' views of management were fairly negative, an
issue that management needs to address. Nurses' ability to work professionally
and autonomously is also important to their satisfaction. There are indications
that nursing supervisory skill sets need to be upgraded in some instances.
PMID- 17039999
TI - Words matter: a proposed nosologic lexicon for sleep breathing.
PMID- 17040000
TI - Neurobehavioral morbidity associated with disordered breathing during sleep in
children: a comprehensive review.
AB - STUDY OBJECTIVES: To comprehensively review research on the association between
childhood sleep-disordered breathing (SDB) and neurobehavioral functioning.
DESIGN: Qualitative and quantitative literature review. SETTING: N/A. PATIENTS OR
PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The findings of
61 studies of the relationship between childhood SDB and neurobehavioral
functioning were critically evaluated and synthesized. There is strong evidence
that childhood SDB is associated with deficits in behavior and emotion
regulation, scholastic performance, sustained attention, selective attention, and
alertness. There is also evidence that SDB has minimal association with a child's
typical mood, expressive language skills, visual perception, and working memory.
Findings have been insufficient to draw conclusions about intelligence, memory,
and some aspects of executive functioning. Mechanisms by which SDB might result
in neurobehavioral morbidity are being explored, but clinical symptoms such as
chronic snoring remain the best predictors of morbidity. Short-term SDB treatment
outcome studies are encouraging, but the long-term outcomes are not known.
Failing to treat SDB appears to leave children at risk for long-term
neurobehavioral deficits. CONCLUSIONS: Childhood SDB is associated with
neurobehavioral morbidity. Applying commonly used guidelines for causal
inference, even in the absence of a much-needed randomized clinical trial, there
is strong evidence of association, consistent findings, and specificity of
effect. There is suggestive evidence that this association fits the expected
temporal pattern and that SDB is a biologically plausible cause of
neurobehavioral deficits. Clinicians should be alert to the coexistence of SDB
symptoms and concerns about a child's academic progress, attention, arousal, or
behavior or emotion regulation.
PMID- 17040001
TI - An epidemiologic study of sleep-disordered breathing symptoms among adolescents.
AB - STUDY OBJECTIVES: To examine the prevalence and distribution of the symptoms of
sleep-disordered breathing (SDB) in a community-based sample of adolescents, and
to assess association of SDB with body mass index, daytime sleepiness, school
performance, and attention-deficit/hyperactivity disorder. DESIGN: Epidemiologic
study of a community-based sample of adolescents and 1 parent with whom separate
structured face to face diagnostic interviews were conducted. SETTING:
Metropolitan Detroit, Michigan, USA. PARTICIPANTS: One thousand fourteen
adolescents aged 13 to 16 years and a paired parent. MEASURES AND RESULTS: SDB
was defined as report of loud snoring, gasping/choking or snorting, awakening
with gasping or choking, or momentary periods of stopped or abnormal breathing
occurring weekly. More than 20% of the adolescents snored at least a few nights
per month, 6% snoring every or nearly every night. Apnea-like symptoms affected
from 2.5% to 6.1% of adolescents. The prevalence of weekly SDB was 6.0% according
to both adolescent and parental report and was twice as likely among African
Americans as Caucasians. The association of body mass index with SDB was twice as
great among Caucasian adolescents as African American adolescents. SDB was
independently associated with excessive daytime sleepiness, poorer grade point
averages, and attention-deficit/hyperactivity disorder-inattention type; each
being more than twice as likely to occur among those with SDB than those without
SDB. CONCLUSIONS: Symptoms of SDB appear to be common among adolescents and
independently associated with short- and longer-term adverse outcomes. These
associations appear to be complex in the population and will require longitudinal
epidemiologic studies to clarify the nature of their relationships and the
opportunities for intervention.
PMID- 17040002
TI - Bruxism in children: effect on sleep architecture and daytime cognitive
performance and behavior.
AB - STUDY OBJECTIVES: Sleep bruxism is an involuntary mandibular movement with tooth
grinding during sleep. The prevalence of sleep bruxism in children is high and
may lead to frequent arousals with altered daytime functioning. We investigated
the sleep architecture, the incidence of gastroesophageal reflux, and the daytime
cognitive behavioral functioning in a group of children with sleep bruxism.
DESIGN-PATIENTS: This prospective pilot study included 10 children.
Polysomnographic data with pH-probe analysis was compared with 10 age- and sex
matched controls. Each patient completed a dental evaluation, a nighttime
polysomnogram, and cognitive behavioral tests (Kaufman Brief Intelligence Test
and Achenbach Child Behavior Checklist). RESULTS: Eight of 10 children had
clinically significant bruxism and the 2 remaining patients had recent teeth
exfoliation. There was no difference on sleep architecture between patients and
controls, except for a higher arousal index for the bruxism group (36.7 vs 20.7,
p < .007). Sleep bruxism occurred more frequently in stage 2 and rapid eye
movement sleep, with arousals in 66% of the cases. There was no relationship of
bruxism to gastroesophageal reflux or intelligence. However, 40% of the patients
had elevated scores on the Achenbach Child Behavior Checklist, indicating
significant attention and behavior problems, and there were moderate correlations
between the arousal index and several of the behavior-problem scales from the
Achenbach Child Behavior Checklist (0.5 to 0.6). CONCLUSIONS: The data suggest
that children with bruxism have a higher arousal index, which may be associated
with an increased incidence of attention-behavior problems. Future studies
investigating pediatric sleep bruxism will need to focus on behavior issues that
may be prevalent in this population.
PMID- 17040003
TI - Recommendations for a standard research assessment of insomnia.
AB - STUDY OBJECTIVES: To present expert consensus recommendations for a standard set
of research assessments in insomnia, reporting standards for these assessments,
and recommendations for future research. PARTICIPANTS: N/A. INTERVENTIONS: N/A.
METHODS AND RESULTS: An expert panel of 25 researchers reviewed the available
literature on insomnia research assessments. Preliminary recommendations were
reviewed and discussed at a meeting on March 10-11, 2005. These recommendations
were further refined during writing of the current paper. The resulting key
recommendations for standard research assessment of insomnia disorders include
definitions/diagnosis of insomnia and comorbid conditions; measures of sleep and
insomnia, including qualitative insomnia measures, diary, polysomnography, and
actigraphy; and measures of the waking correlates and consequences of insomnia
disorders, such as fatigue, sleepiness, mood, performance, and quality of life.
CONCLUSIONS: Adoption of a standard research assessment of insomnia disorders
will facilitate comparisons among different studies and advance the state of
knowledge. These recommendations are not intended to be static but must be
periodically revised to accommodate further developments and evidence in the
field.
PMID- 17040004
TI - Attenuated thermoregulatory response to mild thermal challenge in subjects with
sleep-onset insomnia.
AB - STUDY OBJECTIVES: To determine if heat loss capacity of sleep onset insomniacs
was different from that of healthy sleepers. DESIGN: Measure skin temperature
responses following brief exposure to a warm peripheral thermal challenge (PTC).
SETTING: Sleep research laboratory in South Australia. PARTICIPANTS: Eight
primary insomniacs with sleep onset insomnia according to DSM-IV-TR criteria
(SOI; 5 male, 3 female; mean age +/- SEM = 35.2 +/- 4.2 years) and ten healthy
sleeping control subjects (HS; 7 male, 3 female; mean age = 28.2 +/- 2.8 years).
INTERVENTIONS: Two PTC conditions in counterbalanced order on non-consecutive
days. During each condition, the subject's non-dominant forearm and hand were
immersed for 3 minutes in Warm (45 degrees C) or Control water (i.e. same as the
subject's non-dominant index finger temperature just prior to immersion, range 30
35 degrees C). MEASUREMENTS AND RESULTS: HS had a significantly higher maximum
finger temperature response after immersion than SOI (P < 0.05). Expressed
relative to Control PTC temperatures, the Warm PTC caused a significant increase
in mean finger temperature for HS of 4.1 +/- 0.8 degrees C, compared with SOI of
0.9 +/- 0.4 degrees C. A significant negative relationship was observed between
maximum finger temperature response and self-reported sleep onset latencies (R =
0.57, P < 0.05). There were no main effects of sleep status (SOI vs. HS) or
interactions by time, in skin temperatures measured at either the back of hands
or feet. CONCLUSIONS: SOI were observed to have significantly attenuated
thermoregulatory responses to a mild positive thermal challenge, providing
evidence that impaired heat loss capacity from the periphery is associated with
sleep onset insomnia.
PMID- 17040005
TI - PLMS and PLMW in healthy subjects as a function of age: prevalence and interval
distribution.
AB - STUDY OBJECTIVES: Several studies have demonstrated a positive correlation
between periodic leg movements during sleep (PLMS) and age in healthy subjects.
However, little is known about periodic leg movements during wakefulness (PLMW)
in this population. Although the definitions of PLMS and PLMW specify a typical
intermovement interval of 20 to 40 seconds, scoring criteria allow an
intermovement interval of 4 to 90 seconds. The aim of the present study was to
look at the prevalence and interval distribution of PLMS and PLMW in relationship
with age in a population of healthy subjects. DESIGN: Periodic leg movements were
recorded during 1 night. SETTING: Sleep laboratory, Hopital du Sacre-Coeur de
Montreal. PARTICIPANTS: Sixty-seven healthy subjects aged between 5 and 76 years
(32 F, 35 M). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The presence of PLMS
was rare before the age of 40, but then the index increased dramatically. PLMW
index was higher in younger subjects compared with middle-aged subjects. Interval
histograms of PLMS did not revealed a clear peak in younger subjects. With
advancing age, PLMS interval histograms show a peak around 15 to 35 seconds,
which is not observed in younger subjects. On the other hand, despite high
indexes, PLMW interval histograms do not show a clear peak for any age group.
CONCLUSION: These results illustrate that interval evaluation is an important
feature of the calculation of periodic movements to discriminate spontaneous
motor activity from PLMS or PLMW.
PMID- 17040006
TI - A randomized trial evaluating the effectiveness of sodium oxybate therapy on
quality of life in narcolepsy.
AB - STUDY OBJECTIVES: To evaluate the efficacy of sodium oxybate versus placebo to
improve quality of life in patients with narcolepsy. DESIGN: A multicenter,
double-blind, placebo-controlled trial. SETTING: Outpatient facility of 42 sleep
centers in the United States, Canada, and Europe. PARTICIPANTS: Study
participants were 285 patients with narcolepsy, 16 to 75 years of age, with a
median Epworth Sleepiness Scale score of 18, a Maintenance of Wakefulness Test
sleep latency of 9.56 minutes, and experiencing symptoms of narcolepsy, including
cataplexy and excessive daytime sleepiness with recurrent sleep episodes almost
daily for at least 3 months at the time of enrollment. INTERVENTIONS: Subjects
were gradually withdrawn from narcolepsy medications used for cataplexy,
including antidepressants. Subsequently, participants were randomly assigned to
receive 4.5, 6.0, or 9.0 g per day of sodium oxybate or placebo taken in two
equally divided doses upon retiring to bed and again 2.5 to 4 hours later for 4
weeks during the stable dosing phase. MEASUREMENTS AND RESULTS: The change in
quality of life following the administration of sodium oxybate was measured with
the Functional Outcomes of Sleep Questionnaire. The nightly administration of
sodium oxybate produced significant dose-related improvements in the Total
Functional Outcomes of Sleep Questionnaire score, as well as in the Activity
Level, General Productivity, Vigilance, and Social Outcomes subscales.
CONCLUSIONS: The nocturnal administration of sodium oxybate in patients with
narcolepsy was associated with statistically significant and clinically relevant
improvements in functional status, an important component of quality of life.
PMID- 17040007
TI - Nocturnal overdrive pacing for the treatment of sleep apnea syndrome.
AB - STUDY OBJECTIVES: We investigated the effect of 1 week of nocturnal overdrive
pacing (NOP) on the apnea-hypopnea index (AHI) in patients with a chronically
implanted pacemaker and diagnosed during a screening phase with sleep apnea.
DESIGN: Randomized, single-blind, crossover study. SETTING: University medical
centers in Zurich, Switzerland, and Berlin, Germany. PATIENTS: Nineteen patients
with mild to severe sleep apnea/hypopnea (16 men, mean age = 68.8 +/- 11.4 years)
participated. The individuals did not suffer from permanent atrial arrhythmia,
did not use continuous positive airway pressure, and had been implanted with
atrial or dual-chamber pacemakers. INTERVENTIONS: Nocturnal lower rates were 45
and 75 beats per minute (bpm) at night for the control and NOP arms,
respectively, and daytime lower rates were 60 bpm. Subjects were in each arm for
1 week. MEASUREMENTS AND RESULTS: Heart-rate increase from control (61 +/- 9 bpm)
to NOP (78 +/- 4 bpm) followed by significant reduction in circulation time (24.6
seconds control, 20.7 seconds NOP; p = .04) resulted in no significant change in
AHI (26.8 +/- 17.1/h control, 23.0 +/- 16.7/h NOP; p = .49). Seven subjects
characterized by a higher hypopnea index, less stage 1 and 2 sleep, and less slow
wave sleep improved at least 1 AHI severity level with NOP, mainly attributable
to reduction of hypopneas. CONCLUSION: NOP over a period of 1 week followed by a
reduction in circulation time did not improve AHI in patients with SA. Whether an
improvement by 1 AHI severity level in a specific subset of patients reflects a
true response remains to be elucidated by further studies.
PMID- 17040008
TI - Complex sleep apnea syndrome: is it a unique clinical syndrome?
AB - STUDY OBJECTIVES: Some patients with apparent obstructive sleep apnea hypopnea
syndrome (OSAHS) have elimination of obstructive events but emergence of
problematic central apneas or Cheyne-Stokes breathing pattern. Patients with this
sleep-disordered breathing problem, which for the sake of study we call the
"complex sleep apnea syndrome," are not well characterized. We sought to
determine the prevalence of complex sleep apnea syndrome and hypothesized that
the clinical characteristics of patients with complex sleep apnea syndrome would
more nearly resemble those of patients with central sleep apnea syndrome (CSA)
than with those of patients with OSAHS. DESIGN: Retrospective review SETTING:
Sleep disorders center. PATIENTS OR PARTICIPANTS: Two hundred twenty-three adults
consecutively referred over 1 month plus 20 consecutive patients diagnosed with
CSA. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Prevalence of complex sleep
apnea syndrome, OSAHS, and CSA in the 1-month sample was 15%, 84%, and 0.4%,
respectively. Patients with complex sleep apnea syndrome differed in gender from
patients with OSAHS (81% vs 60% men, p < .05) but were otherwise similar in sleep
and cardiovascular history. Patients with complex sleep apnea syndrome had fewer
maintenance-insomnia complaints (32% vs 79%; p < .05) than patients with CSA but
were otherwise not significantly different clinically. Diagnostic apnea-hypopnea
index for patients with complex sleep apnea syndrome, OSAHS, and CSA was 32.3 +/-
26.8, 20.6 +/- 23.7, and 38.3 +/- 36.2, respectively (p = .005). Continuous
positive airway pressure suppressed obstructive breathing, but residual apnea
hypopnea index, mostly from central apneas, remained high in patients with
complex sleep apnea syndrome and CSA (21.7 +/- 18.6 in complex sleep apnea
syndrome, 32.9 +/- 30.8 in CSA vs 2.14 +/- 3.14 in OSAHS; p < .001). CONCLUSIONS:
Patients with complex sleep apnea syndrome are mostly similar to those with OSAHS
until one applies continuous positive airway pressure. They are left with very
disrupted breathing and sleep on continuous positive airway pressure. Clinical
risk factors don't predict the emergence of complex sleep apnea syndrome, and
best treatment is not known.
PMID- 17040009
TI - Diurnal sex differences in the sleep-wake cycle of mice are dependent on gonadal
function.
AB - STUDY OBJECTIVES: Sex is an important determinant of the pathophysiology of
several disorders that influence and/or impair sleep-wake regulation. To date,
few studies have examined either the role of sex or the gonadal hormones on sleep
and wakefulness. The difficulty in performing well-controlled clinical
experiments on sex and sleep underscores the need for effective animal models to
investigate the influence of the gonadal hormones on sleep-wake states. This
study describes the influence of sex on sleep and wakefulness in mice, the
primary mammalian genetic model for sleep analysis, and tests the hypothesis that
gonadal function drives sex differences in sleep-wake states. DESIGN:
Electroencephalogram/electromyogram sleep-wake patterns were recorded in intact
and gonadectomized male and female C57BL/6J mice maintained on a 14-hour light:10
hour dark schedule. Following a 24-hour baseline recording, mice were sleep
deprived during the light phase by gentle handling and given a 10-hour recovery
opportunity during the immediate dark phase. MEASUREMENTS AND RESULTS: Intact
female mice spent more time awake than intact males during 24 hours of baseline
recording at the expense of non-rapid eye movement (NREM) sleep. Though the
recovery response of NREM sleep was similar between males and females, when
examined in reference to baseline levels, females exhibited a more robust
recovery response. Gonadectomy in males and females reduced or eliminated the
majority of sex differences in sleep architecture and homeostasis. CONCLUSIONS:
These data demonstrate that the gonadal hormones influence the amount,
distribution, and intensity of sleep but do not account for all sex differences
in the sleep-wake cycle.
PMID- 17040010
TI - Sex differences in sleep: the response to sleep deprivation and restraint stress
in mice.
AB - STUDY OBJECTIVES: Numerous clinical studies and sleep surveys have shown
pronounced sex differences in the occurrence of insomnia and other sleep
pathologies. It has been suggested that sex differences in sleep, while subtle
under baseline conditions, may increase in magnitude under biological or
environmental challenges. However, controlled and experimental studies on sleep
under challenged conditions rarely include female subjects. In this context, we
examined sex differences in sleep in the mouse, not only under baseline
conditions, but also after sleep deprivation and restraint stress. DESIGN: Adult
male and female C57BL/6J mice were implanted with electrodes to record sleep-wake
architecture and sleep electroencephalogram under baseline conditions and after 6
hours of sleep deprivation or 1 hour of restraint stress at the beginning of the
daily light phase. RESULTS: Although baseline sleep patterns slightly differed
between the sexes, the homeostatic recovery response to sleep deprivation was
similar. In contrast, the changes in sleep after restraint stress were markedly
different between male and female mice, with males displaying a stronger initial
suppression of sleep and a stronger rebound of rapid-eye-movement sleep later in
the recovery phase. CONCLUSIONS: In mice, the fundamental homeostatic properties
of sleep regulation may not differ between the sexes, but the way sleep is
affected and disrupted by environmental influences may be sex dependent. The
latter may reflect sex differences in stress sensitivity.
PMID- 17040011
TI - A reassessment of the hyperphagia/weight-loss paradox during sleep deprivation.
AB - STUDY OBJECTIVES: Sleep deprivation is a well-known paradigm to investigate the
deleterious effects of prolonged wakefulness. Previous studies have shown that,
during sleep deprivation, rats are hyperphagic but, paradoxically, lose body
weight. This phenomenon has been attributed to increased metabolism. However,
most previous studies have failed to account for food spillage, which may be
considerable during sleep deprivation. DESIGN: In the present study, we revisited
the issue of feeding changes in sleep-deprived rats and introduced different
procedures to allow accurate estimation of food spillage prior to, during, and
after 120 hours of sleep deprivation by a single platform technique. SETTING:
Animal Sleep Research Laboratory, Psychobiology Department, Universidade Federal
de Sao Paulo, Brazil. MEASUREMENTS AND RESULTS: The main finding was that, once
corrected for spillage, food intake was not significantly increased during sleep
deprivation. Increases in food removed from feeders were accompanied by
proportional increases in food spillage, resulting in no net changes in food
intake. Further, weight loss did occur during the sleep-deprivation period,
especially in the first 24 hours, and it was actually explained by a reduction in
food intake. CONCLUSION: The hyperphagia/weight-loss paradox previously seen
during prolonged sleep deprivation does not necessarily occur with shorter
periods of deprivation. Although we found no evidence of hyperphagia for up to 5
days of sleep deprivation in chow-fed rats, our data suggest that an impairment
in the ability to increase food intake in response to increased energy
expenditure contributes to the energy deficit during sleep deprivation in rats.
PMID- 17040012
TI - Technical innovations and the evolution of endoscopic sinus surgery.
AB - Since the introduction of endoscopic sinus surgery, a number of significant
technological advances, as well as an improved understanding of disease
pathogenesis and management, have enabled major evolutions in surgical
techniques. Modifications to surgical instruments, imaging, the development of
the microdebrider, and other newer instrumentation have all contributed to the
current level of patient success associated with endoscopic intranasal
techniques. At the same time, it has become evident that anatomic variations are
less important in the pathogenesis of chronic rhinosinusitis than was previously
thought, and that ventilation alone is insufficient to resolve well-established
disease. This paper reviews the changes that have occurred in endoscopic sinus
surgery over the past 20 years since the techniques were first introduced into
the United States, and the technologies that have enabled these changes and the
development of extended endoscopic techniques. Continuing developments of
interactive computer-guided surgery, endoscopic 3-dimensional imagery, robotics,
and improved adjunctive therapies will further extend the role of endoscopic
transnasal approaches to an expanded number of skull base and intracranial
lesions.
PMID- 17040013
TI - Frontal sinus surgery: its evolution, present standard of care, and
recommendations for current use.
AB - From a historical perspective, frontal sinus surgery has evolved from radical,
highly invasive, disfiguring approaches to function-preserving, minimally
invasive, and non-disfiguring intranasal procedures. Most sinus surgeons would
agree that a sound surgical procedure is one that relieves patients' symptoms and
provides a safe sinus in which future intracranial and orbital complications will
not occur. For the future, sinus surgeons are searching for the ideal procedure,
ie, one that is minimally invasive, reversible, and ensures the patient a safe
frontal sinus for the long term. The ideal surgery will also leave minimal
morbidity, will leave no cosmetic defect, and will allow for easy postoperative
surveillance. To achieve this new standard in frontal sinus surgery, continuous
refinements are required in the medical management and understanding of the
disease processes that undermine long-term surgical success. Further advancements
in instrumentation and visualization techniques are also necessary to enhance
surgical precision, spare mucosa, and prevent the scarring and neo-osteogenesis
that may cause surgical failures. Perhaps the most important development may be
in the selection criteria for appropriate candidates who will benefit most from
frontal sinus surgery.
PMID- 17040014
TI - Sinonasal mucociliary clearance in health and disease.
AB - Although much has been elucidated in the past 170 years concerning the precise
mechanism of ciliary function in the healthy or diseased human respiratory
system, significant questions remain. The first description of ciliary action is
credited to Sharpey in 1835. However, the importance of mucosal function was not
apparent until Hilding's investigations of the postsurgical canine sinus
demonstrated scar formation and disruption of mucociliary clearance.
Subsequently, several techniques for mucosal coverage of exposed bone, most
notably by Sewall and Boyden, were reported. The underlying physiology explaining
the importance of the mucosa and the concept of mucosal preservation became
apparent with the description of the sinonasal mucociliary flow patterns by
Messerklinger; and thus the restoration of natural sinus physiology, ie,
mucociliary clearance, became the goal of both medical and surgical treatment of
sinonasal inflammatory disease. Clearance of benign and pathological substances
in the mucus is governed by the propulsive force of the beating cilia and the
physical characteristics of the overlying mucus. The respiratory cilia
continually beat in a coordinated fashion, and in times of stress (eg, exercise,
infection, or fever) ciliary beat frequency increases to accelerate mucus
clearance. Thus, upper airway ciliary motility is under dynamic modulation.
Multiple investigations incontrovertibly demonstrate a marked decrease in
sinonasal mucociliary clearance in patients with chronic rhinosinusitis. Possible
explanations for this finding are 1) a reduced basal ciliary beat frequency, 2)
an alteration of the viscoelastic properties of airway secretions, and/or 3) a
blunted dynamic response of sinonasal cilia to environmental stimuli. Studies of
the first two explanations yield conflicting results, and to date, the third
possibility remains uninvestigated. A review of the current understanding of the
cellular regulation of respiratory ciliary activity and its contribution to
chronic rhinosinusitis is presented.
PMID- 17040015
TI - Fungus and chronic rhinosinusitis: from bench to clinical understanding.
AB - Although fungus-related sinusitis has been described for at least 2 centuries, a
more detailed pathologic description of the problem as it relates to eosinophilic
disease was not detailed until 1983, when "allergic fungal sinusitis" was
described histopathologically. Until then, most fungal sinus disease was
perceived to occur in immunosuppressed diabetic patients with invasive fungus. It
is now acknowledged that depending upon the immune status of the host, fungus
related sinus disease can take several forms. Interest in this subject matter was
intensified in 1999, when it was suggested that fungi might be an important cause
of most cases of chronic rhinosinusitis. This hypothesis remains controversial,
and there is mounting evidence to support the multifactorial nature of chronic
rhinosinusitis, which may include fungus. In fact, etiologic factors for all
forms of fungus-related sinus disease are still poorly understood. The prevalence
of the disease and the dominant fungal pathogen appear to vary in different
geographic regions and probably are related to individual host conditions.
Immunoglobulin E-mediated allergic reactions to mold appear to be associated with
disease in some patients, but not in all. Although antifungal therapy is known to
be lifesaving for invasive disease, its role in extramucosal disease is less well
defined. Preliminary trials suggest that some systemic and topical antifungal
agents are of clinical benefit in extramucosal disease. Since sinus fungi are
rarely invasive in immunocompetent individuals, it is not clear whether the
effects of the antifungal treatments are a result of the antifungal action
itself, or due to additional properties these drugs possess. This review
summarizes the available data and presents some of our clinical and experimental
findings as to the role of fungus in chronic rhinosinusitis.
PMID- 17040016
TI - Bacterial biofilms in chronic rhinosinusitis.
AB - Chronic sinusitis is a prevalent, debilitating condition, and a subpopulation of
patients fails to respond to either medical or surgical intervention. Bacterial
biofilms are 3-dimensional aggregates of bacteria that have special properties
due to their group structure, including increased resistance to antibiotics in
some forms. They have been shown to play a major role in many chronic infections,
including cystic fibrosis, endocarditis, and otitis media. Evidence now suggests
that they may play an important role in chronic sinusitis. Our laboratory has
identified the presence of biofilms in sinonasal mucosa isolated from human
patients and on stents removed after frontal sinus surgery. In addition, biofilms
have been found on the sinus epithelium of rabbits infected with Pseudomonas
aeruginosa, but not in rabbits infected with non-biofilm-forming P. aeruginosa
mutants. This animal model can provide opportunities to address the functional
significance of biofilm production in the sinus cavities. A further understanding
of the role of bacterial biofilms may lead to the development of more appropriate
therapies for the treatment and prevention of chronic sinusitis.
PMID- 17040017
TI - Surfactant and its role in chronic sinusitis.
AB - Although numerous studies have focused on the nature and defensive role of
surfactant in the lower airways, relatively little is known about its role in the
upper airways. Decreased levels of the main component of surfactant-
phospholipids--have been implicated in atrophic rhinitis. The lamellar body
arrangement of phospholipids has now been demonstrated in both normal and
diseased sinus tissue, resulting in the implication that these structures may
play a crucial role in mucociliary clearance against inhaled pathogens, as well
as in the regulation of mucous viscosity. Furthermore, they may be secreted from
sinonasal ciliated epithelium. Surfactant proteins (SPs) make up a relatively
smaller proportion of surfactant, but appear to have an important role in innate
immunity. Altered levels of SPs have been observed in a number of respiratory
tract diseases. These SPs may prove to play a significant role in chronic
sinusitis. Demonstrated expression of SP-A and SP-D in diseased and normal sinus
tissue may mean that these SPs are excreted into the airway-lining fluid of the
sinuses. Additionally, initial contact and interaction between pathogens and SP-A
and SP-D may occur relatively early after inhalation and deposition into the
mucus of the respiratory tract. These findings may lead to potential therapeutic
options for difficult-to-treat sinus disease in the future.
PMID- 17040018
TI - Transnasal endoscopy-assisted skull base surgery.
AB - Skull base surgery (SBS), which originated in the 19th century, became refined in
the 20th century in parallel with technological advancements and is now in the
midst of further refinements largely driven by advances in endoscopic sinus
surgery. With the development of modern SBS, lesions that were once inoperable
and potentially fatal can now be eradicated successfully by means of endoscopy
assisted procedures that reduce or completely eliminate intracranial trauma,
minimize postsurgical morbidity, and make full recovery possible. It is
absolutely mandatory to have the appropriate instrumentation for endoscopy
assisted SBS. Among the new technologies available are advanced endoscopes, high
speed suction irrigation drills, digital video cameras, computed tomography and
magnetic resonance imaging, and systems for 3-dimensional computer-assisted image
guided surgical navigation. An experienced endoscopic surgeon working with
multidisciplinary teams, and using new instrumentation and techniques, can bring
SBS to new levels of success in the 21st century.
PMID- 17040019
TI - Evolution of medical management of chronic rhinosinusitis.
AB - Chronic rhinosinusitis (CRS) is a surprisingly common, poorly defined, and
notoriously difficult-to-treat disease. It has a complex pathophysiology that
often, but not always, involves nasal or paranasal sinus infection. Anatomic
variations that predispose the sinuses to obstruction may play a role, but are
unusual sole causes of chronic disease. Other possible causative factors include
allergic or nonallergic inflammation, mucociliary dysfunction, aspirin
intolerance (Samter's triad), immunodeficiency, and cystic fibrosis. Although a
majority of patients achieve long-term relief from CRS after successful
endoscopic sinus surgery, a significant proportion do not, and are likely to
benefit from sustained postsurgical medical therapy. Medical therapy for CRS may
include treatment with corticosteroids, antibiotics, antifungal agents,
antihistamines, leukotriene modifiers, nasal decongestants, mucolytics, and nasal
irrigations. The selection of appropriate medical therapy is based on endoscopic
evaluation, sinus cultures, and symptoms. Computed tomography, the imaging
standard for evaluation of the sinuses, provides information about the extent and
distribution of mucosal disease beyond what is visible endoscopically. Because it
fails to provide information on the origin of the mucosal changes, computed
tomography provides limited information to guide medical therapy.
PMID- 17040020
TI - Progress in sinonasal imaging.
AB - Imaging of sinonasal structures has evolved from standard radiographs to the much
more complicated and informative techniques used today. The plain radiograph was
useful when the surgical techniques practiced were primarily aimed at the
maxillary and frontal sinuses. With a better understanding of the mucociliary
clearance of the nasal cavity and the paranasal sinuses, the surgical technique
was shifted to the ethmoid sinuses and became more focal, thus needing a better
understanding and display of the intricate morphology of the nasal cavity and
paranasal sinuses. Polytomography was a step above plain radiographs and was
first used in the display of the regional anatomy for the development of
functional endoscopic sinus surgery. Polytomography was quickly replaced by
computed tomography, as this imaging technique provides a much more detailed view
of the sinonasal architecture than does polytomography. Magnetic resonance
imaging has also shown usefulness in imaging this morphological area, as it
provides better soft tissue resolution, but it does not allow good visualization
of bony structures. Newer computer systems with software capable of
reconstructing the digitized information into a 3-dimensional display further
enhance our understanding of the regional morphology and afford an improved means
of correlating the imaging and endoscopic information. Furthermore, stereotactic
navigation systems allow surgeons the ability to visualize the endoscope
instrument tip position, as instruments are actively being used during surgery,
on the computed tomographic and/or magnetic resonance images. There is a
persistent trend toward reducing the size of the imaging equipment to render it
more mobile (computed tomography) and adapt it for operating room use.
PMID- 17040021
TI - Approval of nonprescription sale of Plan B muddies ethical waters.
AB - The best way to minimize conflicts and confusion over ethical and religious
issues is to understand provider and patients' rights and have a solid plan in
place, say ED experts. Make sure you know what your providers are and are not
willing to do. Staff members who refuse care still are obligated to inform
patients how they can receive it. Have other physicians or nurses available to
provide care when such situations arise.
PMID- 17040022
TI - EDs pool resources to weather flood.
AB - When disaster strikes your community, creativity can go a long way toward keeping
your ED up and running, but cooperating with neighboring facilities can double
your available resources in a hurry. Contact all unscheduled staff members and
request that they accept additional shifts during the crisis. If nearby
facilities are shut down, contact their manager to ascertain availability of
their staff and supplies. Seek additional staffing help from local residency
programs.
PMID- 17040023
TI - Hospital planning ahead for bird flu pandemic.
AB - In preparing your department's response to a pandemic, it's best to plot out
worst-case scenarios. Once the scenarios have been created, explore all possible
solutions to equipment and staffing shortages. Since existing capacity will be
insufficient, identify in advance alternative sites for treating victims. Stay
abreast of new equipment developments, such as multiple ventilators, that may
help deal with the added volume of immune compromised patients. Recognize that
the level of care will be reduced, and adjust your emergency preparedness
protocols accordingly.
PMID- 17040024
TI - Satisfaction turnaround requires persistence.
AB - The key to improving patient satisfaction scores and maintaining those
improvements lies not only in devising a successful strategy, but in ensuring
that your staff consistently follow the new procedures. Institute simple changes,
such as stools in exam rooms, to ensure closer physician-patient contact. Post
satisfaction scores in the department to make the staff aware of how they are
performing. Use focus groups and outside experts to generate new ideas for you to
implement with your staff.
PMID- 17040025
TI - Will new e-facility help fight ED overcrowding?
AB - The use of telemedicine to diagnose patients before they come to the ED may
benefit the operation of your ED, as well as the emergency medicine system in
general. Potential advantages include the following: By identifying nonemergent
cases, it can help reduce overcrowding. Since nonemergent patients have the
longest wait times, it may reduce rates for patients who leave without being seen
and boost satisfaction. It can help avoid unnecessary transfers to and from the
ED.
PMID- 17040027
TI - Patch Adams, MD: healthcare activist.
PMID- 17040026
TI - Quality- and severity-based payment: will you receive what you earn?
AB - Pay-for-performance programs that call for healthcare providers to meet external
quality metrics are being proposed by the Centers for Medicare and Medicaid
Services and other payers in order to increase the value of dollars spent on
health care. While linking payment with the quality of health care may be a
laudable goal, such programs have the potential to test the relationships between
hospitals and physicians and unfairly penalize hospitals for factors that are
beyond their control. In the following article, HFMA, with sponsorship from 3M
Health Information Systems, asks five industry leaders to share their thoughts
about what pay-for-performance programs may entail, how these programs and
severity-based payment adjustments may affect their healthcare facilities, and
strategies healthcare organizations should employ to best prepare.
PMID- 17040028
TI - Clearing the way for transparency in health care.
PMID- 17040029
TI - 'What's good today isn't going to be nearly enough tomorrow'.
PMID- 17040030
TI - Bariatric surgery coverage decision: opportunities and limitations.
AB - CMS's national coverage decision on bariatric surgery has implications for obese
patients, insurers, and the physicians and hospitals that treat those patients.
Other insurers may follow Medicare's lead, causing an increase in patient volume.
As the number of approved facilities increases, the number of procedures
performed will grow, bringing in new revenue.
PMID- 17040031
TI - The myths of benchmarking healthcare IT spending.
AB - Healthcare organizations should make those IT investments that they believe can
be managed to achieve an acceptable return. They should make investment decisions
based on the merits of the IT proposal, not because they have to catch up to
another industry, such as banking.
PMID- 17040032
TI - Picking up the pace: accelerating your pricing competency.
AB - There are at least four things your organization can do to accelerate progress
toward more defensible, margin-enhancing prices and rates: Choose the right
starting point. Adopt a pricing formula. Create a pricing toolkit. Align pricing
roles and responsibilities.
PMID- 17040033
TI - Developing a defensible pricing strategy. Hospital pricing is a science, not an
art.
AB - A more sophisticated approach to establishing hospital pricing strategies should
include: Reevaluating billing policies and processes to establish payment plans
and protocols for collection. Establishing a predictable and accurate pricing
schedule for all services based on variables such as market, cost, and fee
schedules. Leveraging IT to guide decision making Informing hospital boards of
the basis for pricing strategies.
PMID- 17040034
TI - Pricing and paying for proactive care.
AB - Now that proactive health services are increasingly being paid for by third
parties, entirely new bases for and kinds of pricing are being practiced. New
options becoming common include: Pay-for-performance bonuses. Bonuses based on
achieving disease-specific or risk-specific outcomes. Gainsharing arrangements.
PMID- 17040035
TI - Capacity management and patient throughput: putting this problem to bed.
AB - Organizations dealing with capacity issues have several options, including:
Increasing capacity within current licensed space. Building more beds. Adding
functional capacity through improving patient throughput. Smoothing demand
through variability isolation.
PMID- 17040036
TI - Lean-Six Sigma: tools for rapid cycle cost reduction.
AB - Organizational costs can be grouped as process cost, cost of quality, and cost of
poor quality. Providers should train managers in the theory and application of
Lean-Six Sigma, including the seven categories of waste and how to remove them.
Healthcare financial executives should work with managers in eliminating waste to
improve service and reduce costs.
PMID- 17040037
TI - Beyond budgeting in an IDS: the Park Nicollet experience.
AB - Beyond budgeting transcends the limitations of traditional budgeting by replacing
fixed financial targets with targets based on key performance indicators. For
Park Nicollet Health Services, the decision to implement beyond budgeting
coincided with a larger move to adopt a Lean approach to management. Park
Nicollet's process to implement beyond budgeting-from submission of the initial
proposal through two test runs with process refinements to full implementation
lasted about one year, from January 2005 to January 2006.
PMID- 17040038
TI - A formula for success for women (and men!) in leadership.
PMID- 17040039
TI - Why women's health business development?
AB - Studies show that women are the primary healthcare decision makers in this
country; 66 cents of every healthcare dollar is spent on or by women. The
Department of Health and Human Services will spend $8.3 billion on women's health
in 2006.
PMID- 17040040
TI - Sleep deficit: the performance killer. A conversation with Harvard Medical School
Professor Charles A. Czeisler.
AB - Companies today glorify the executive who logs 100-hour workweeks, the road
warrior who lives out of a suitcase in multiple time zones, and the negotiator
who takes a red-eye to make an 8 A.M. meeting. But to Dr. Charles A. Czeisler,
the Baldino Professor of Sleep Medicine at Harvard Medical School, this kind of
corporate behavior is the antithesis of high performance. In fact, he says, it
endangers employees and puts their companies at risk. In this interview, Czeisler
describes four neurobiological functions that affect sleep duration and quality
as well as individual performance. When these functions fall out of alignment
because of sleep deprivation, people operate at a far lower level of performance
than they would if they were well rested. Czeisler goes on to observe that
corporations have all kinds of policies designed to protect employees- rules
against smoking, sexual harassment, and so on-but they push people to the brink
of self-destruction by expecting them to work too hard, too long, and with too
little sleep. The negative effects on cognitive performance, Czeisler says, can
be similar to those that occur after drinking too much alcohol: "We now know that
24 hours without sleep or a week of sleeping four or five hours a night induces
an impairment equivalent to a blood alcohol level of .1%. We would never say,
'This person is a great worker! He's drunk all the time!' yet we continue to
celebrate people who sacrifice sleep for work." Czeisler recommends that
companies institute corporate sleep policies that discourage scheduled work
beyond 16 consecutive hours as well as working or driving immediately after late
night or overnight flights. A sidebar to this article summarizes the latest
developments in sleep research.
PMID- 17040041
TI - The tools of cooperation and change.
AB - Employers can choose from lots of tools when they want to encourage employees to
work together toward a new corporate goal. One of the rarest managerial skills is
the ability to understand which tools will work in a given situation and which
will misfire. Cooperation tools fall into four major categories: power,
management, leadership, and culture. Choosing the right tool, say the authors,
requires assessing the organization along two critical dimensions: the extent to
which people agree on what they want and the extent to which they agree on cause
and effect, or how to get what they want. The authors plot on a matrix where
various organizations fall along these two dimensions. Employees represented in
the lower-left quadrant of the model, for example, disagree strongly both about
what they want and on what actions will produce which results. Those in the upper
right quadrant agree on both dimensions. Different quadrants call for different
tools. When employees share little consensus on either dimension, for instance,
the only methods that will elicit cooperation are "power tools" such as fiat,
force, and threats. Yugoslavia's Josip Broz Tito wielded such devices
effectively. So did Jamie Dimon, current CEO of J.P. Morgan Chase, during the
bank's integration with Bank One. For employees who agree on what they want but
not on how to get it--think of Microsoft in 1995--leadership tools, such as
vision statements, are more appropriate. Some leaders are blessed with an
instinct for choosing the right tools--Continental Airlines' Gordon Bethune,
General Electric's Jack Welch, and IBM's Lou Gerstner are all examples. Others
can use this framework to help select the most appropriate tools for their
circumstances.
PMID- 17040042
TI - Ideas as art. Interview by Dane Cutu.
AB - Three years ago, consultants Laurence Prusak and Thomas H. Davenport asked
prominent management thinkers to name their gurus and reported the results in
HBR. James G. March appeared on more lists than any other person except Peter
Drucker. A professor emeritus in management, sociology, political science, and
education at Stanford University, March has taught courses in subjects as diverse
as organizational psychology, behavioral economics, leadership, rules for killing
people, friendship, computer simulation, and statistics. He is perhaps best known
for his pioneering contributions to organization and management theory. March's
accomplishments in that field, and in many others, have conferred on him an
almost unprecedented reputation as a rigorous scholar and a deep source of
wisdom. As University of Chicago professor John Padgett wrote in the journal
Contemporary Sociology, "March's influence, unlike that of any of his peers, is
not limited to any possible subset of the social science disciplines; it is
pervasive." March approaches thought aesthetically; he cares that ideas have
"some form of elegance or grace or surprise." His poetic sensibility can be felt
in the metaphors he has created over the years--the "garbage can theory" of
organizational choice, for instance, and the "hot-stove effect" in learning. In
this edited interview with HBR senior editor Diane Coutu, March shares his
thinking on aesthetics, leadership, the role of folly, and the irrelevance of
relevance when it comes to the pursuit of ideas. He also comments on the
fundamental differences between academic and experiential knowledge, underscoring
the need for both.
PMID- 17040043
TI - Meeting the challenge of corporate entrepreneurship.
AB - To be competitive, companies must grow innovative new businesses. Corporate
entrepreneurship, however, isn't easy. New ventures face innumerable barriers and
seldom mesh smoothly with well-established systems, processes, and cultures.
Nonetheless, success requires a balance of old and new organizational traits-and
unless companies keep those opposing forces in equilibrium, their new businesses
will flounder. The authors describe the challenges companies face when they
pursue new businesses, as well as the usual problematic responses to those
challenges. Such companies, they say, must perform three balancing acts: Develop
strategy by trial and error, which includes narrowing potential choices, learning
from small samples, using prototypes to test business models, tracking progress
through nonfinancial measures, and knowing how and when to pull the plug on a new
venture. Find the best combination of old and new operational processes by
staffing new ventures with "mature turks", changing veterans' thinking, knowing
which capabilities to develop and which to acquire, and having old and new
businesses share responsibility for operating decisions. Strike the right balance
of integration and autonomy by assigning both corporate and operating sponsors to
new ventures, establishing criteria for handoffs to existing divisions, and using
creative organizational structures. The authors provide a detailed look at IBM's
Emerging Business Opportunity system, which manages all these balancing acts
simultaneously.
PMID- 17040044
TI - Can science be a business? Lessons from biotech.
AB - In 1976, Genentech, the first biotechnology company, was founded by a young
venture capitalist and a university professor to exploit recombinant DNA
technology. Thirty years and more than 300 billion dollars in investments later,
only a handful of biotech firms have matched Genentech's success or even shown a
profit. No avalanche of new drugs has hit the market, and the long-awaited
breakthrough in R&D productivity has yet to materialize. This disappointing
performance raises a question: Can organizations motivated by the need to make
profits and please shareholders successfully conduct basic scientific research as
a core activity? The question has largely been ignored, despite intense debate
over whether business's invasion of basic science-long the domain of universities
and nonprofit research institutions- is limiting access to discoveries, thereby
slowing advances in science. Biotech has not lived up to its promise, says the
author, because its anatomy, which has worked well in other high-tech sectors,
can't handle the fundamental challenges facing drug R&D: profound, persistent
uncertainty and high risks rooted in the limited knowledge of human biology; the
need for the diverse disciplines involved in drug discovery to work together in
an integrated fashion; and barriers to learning, including tacit knowledge and
murky intellectual property rights, which can slow the pace of scientific
advance. A more suitable anatomy would include increased vertical integration; a
smaller number of closer, longer collaborations; an emphasis by universities on
sharing rather than patenting scientific discoveries; more cross-disciplinary
academic research; and more federal and private funding for translational
research, which bridges basic and applied science. With such modifications,
science can be a business.
PMID- 17040045
TI - What business are you in? Classic advice from Theodore Levitt.
AB - For all the talk about management as a science, experienced executives know that
strategic decisions and tactics depend heavily on context. No one understood this
better than Theodore Levitt (1925-2006). A Harvard Business School professor
renowned as a founder of modern marketing, he sought above all to use his
knowledge to serve the needs of businesspeople. In a series of powerfully
insightful--and delightfully written--essays in Harvard Business Review, he
provoked readers to reexamine their settled thinking about vital issues so that
they could better meet the needs of customers. Levitt had the gifts of
provocation and generalization, offering ideas that startled readers but
compelled them to think creatively and intelligently about their companies.
Writing in a period when business was held in far less esteem than it is today,
he rejected the easy contempt that many intellectuals had for managers and
consumers. Levitt carried that practical approach to his tenure at Harvard
Business Review from 1985 to 1989. As one of HBR's most intellectual and most
populist chief editors, he understood that the magazine's main purpose was to
serve as a kind of sophisticated translation, clarifying authors' raw-and
sometimes rough-ideas for impatient, time-pressed readers. This tribute, a look
into one of business's great minds, offers excerpts from six of Levitt's most
influential HBR articles: "Marketing Myopia" (July-August 1960) "After the Sale
Is Over..."(SeptemberOctober1983) "Marketing Success Through Differentiation-of
Anything" (January-February 1980) "Production-Line Approach to Service"
(September-October 1972) "The Globalization of Markets" (May-June 1983)
"Creativity Is Not Enough" (May-June 1963).
PMID- 17040046
TI - 10 questions for Elizabeth Edwards.
PMID- 17040047
TI - My right hand.
PMID- 17040048
TI - What's killing the sea otters.
PMID- 17040049
TI - Sleep, snoring and the blues.
PMID- 17040050
TI - The real skinny.
PMID- 17040051
TI - [Holmium laser enucleation of the prostate: the Kobe City General Hospital
experience].
AB - Between October 2004 and August 2005, 43 patients with the mean age of 70.9
(ranging 57-83) years, who had lower urinary tract symptoms underwent holmium
laser enucleation of the prostate (HoLEP) at our hospital. The mean operative
time, change in hemoglobin and resected tissue weight were 193 (83-390) minutes,
2.1 (-5.3 -/+ 1.3) g/dl and 40.2 (6.3-90.9) g, respectively. The mean
postoperative urethral catheter time and postoperative hospital stay were 1.7 and
5.5 days, respectively. Minor prostatic capsular perforation and bladder mucosal
injuries in 18 cases without need of additional interventions or treatments.
Blood transfusion for preoperative anemia was needed in one case.
Postoperatively, high fever occurred in 6 cases including sepsis in one case,
while recatheterization was needed in 2 cases because of urination difficulty.
After discharge, meatal stenosis was found in 7 cases, urethral stenosis in 3
cases including 2 cases with preoperative urethral stenosis. Scrotal abscess
developed after acute epididymitis in one case. Transient urinary incontinence
reported in 12 cases, which requires medication or more than 1 pad per day. HoLEP
improved international prostate symptom score, quality of life score, peak
urinary flow rates and postvoiding residual urine volumes immediately and
significantly. HoLEP is a feasible and effective procedure to relieve lower
urinary tract symptoms, although technical and instrumental advances are required
to reduce the operative time and complications.
PMID- 17040052
TI - [Effect of oral lactosucrose supplementation on human enteric oxalate-degrading
bacteria].
AB - A variety of oxalate-degrading bacteria including Oxalobacter formigenes and some
species of Bifidobacterium are known to colonize the human intestinal tract. Oral
lactosucrose supplementation promotes the growth of Bifidobacterium in the human
intestine. Therefore, we investigated the effect of oral lactosucrose
supplementation on enteric oxalate-degrading bacteria in twelve healthy men (age
ranging from 25 to 39 years). Lactosucrose was orally administered 10 g daily for
2 weeks without restriction of dietary intake. The total number of oxalate
degrading bacteria in feces and the 24-hour urinary excretion of oxalate were
examined before and after lactosucrose supplementation. The total number of
oxalate degrading-bacteria was significantly increased by lactosucrose
supplementation (9.20 +/- 0.44 versus 9.77 +/- 0.46, p<0.05), although there was
no significant change in the urinary oxalate excretion. The oxalate degrading
bacteria isolated from feces was biochemically identified as Bifidobacterium
adolescentis. In conclusion, oral supplementation of 10 g lactosucrose daily for
2 weeks was effective in multiplying oxalate-degrading bacteria, but not in
reducing urinary oxalate excretion under free non-restricted dietary intake. In
addition, it was suggested that various species of Bifidobacterium were related
to degradation of oxalate in the human intestine.
PMID- 17040053
TI - [Second-line chemotherapy with gemcitabine and cisplatin for urothelial cancer
previously treated with or resistant to M-VAC therapy].
AB - We evaluated the efficacy of gemcitabine-cisplatin (GC) therapy as a second line
chemotherapy for recurrent urothelial cancer previously treated with or resistant
to methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) therapy. Four
patients who had recurrent cancer after adjuvant M-VAC therapy and five patients
with resistant lesions to M-VAC were treated by GC. Of the nine patients, three
completely responded to GC and three obtained partial response. These complete
responders were cancer-free for 34, 32 and 24 months. In one partial responder,
the metastatic masses have been decreasing in size for 12 months after completion
of GC therapy. Our findings suggested that GC would be useful as a second line
chemotherapy for urothelial cancer previously treated with M-VAC.
PMID- 17040054
TI - [Does early vascular access intervention therapy reduce acute obstruction and
reconstruction of arterial-venous fistula?].
AB - Acute vascular access (VA) obstruction is one of the most common complications
for hemodialysis patients and medical professions. We performed early vascular
access intervention therapy (VAIVT) to reduce the incidence of acute VA
obstruction, VAIVT and fistula reconstruction. During a 2-year period, we
performed 125 procedures of VAIVT in 145 cases in 50 patients who underwent
arterio-venous fistula angiography. We performed early VAIVT within two weeks
since we clinically found VA stenosis. The 125 procedures of VAIVT (95 non
thrombosed cases, 30 thrombosed cases) involved 86 native fistulas (74 non
thrombosed, 12 thrombosed) and 39 graft fistulas (21 non-thrombosed, 18
thrombosed). Prevalence of thrombosed cases was significantly higher in graft
fistula than in native fistula (P<0.001). The primary patency rate in 50 patients
at 6, 12 and 24 months was 62.1, 46.9 and 41.7%, respectively, while the
secondary patency rate was 93.7, 90.7 and 86.6%, respectively. The highest
primary patency rate was found in the non-thrombosed group with native fistula
and the lowest secondary patency rate was found in the thrombosed group with
graft fistula. By comparing the results of this study with the events for the
previous 2 years, the total VAIVT number was almost the same. The number of non
thrombosed cases increased significantly from 54 to 95, and those of thrombosed
cases decreased from 68 to 30 (P < 0.001). The number of fistula reconstructions
significantly decreased from 59 to 22 (P<0.001). Early VAIVT for VA stenosis
could decrease acute VA obstruction and fistula reconstruction without increasing
the total number of VAIVT.
PMID- 17040055
TI - [Solitary fibrous tumor of a kidney: a case report].
AB - We report a case of solitary fibrous tumor (SFT) arising from a kidney. The
patient was an 18-year-old female who visited our hospital with the complaint of
left abdominal pain. Computed tomography revealed a slightly enhanced tumor of
approximately 3 cm in diameter near the upper calyx of the left kidney. Renal
cell carcinoma was suspected, and left nephrectomy was performed under
laparoscopy. Histopathological examination revealed proliferation of CD34
positive spindle-shaped cells, and a diagnosis of SFT was made. There has been no
local recurrence or distant metastasis for 15 months after the operation.
PMID- 17040056
TI - [A case of retroperitoneal schwannoma extracted by a nerve sparing procedure
under microscopic surgery].
AB - We report a case in which we extracted retroperitoneal schwannoma by a nerve
sparing procedure under microscopic surgery. A 63-year-old male was diagnosed
with left ureter stone and left hydronephrosis. A left retroperitoneal tumor was
found by the abdominal ultrasound sonography. Abdominal computed tomography and
magnetic resonance imaging revealed the mass 20 mm in diameter in the
retroperitoneal cavity. We considered that the tumor arose from the left femoral
nerve, and removed it under microscopic surgery. There was no malignancy. There
was neither recurrence nor neuropathy after operation. Since it is rare to find
the origin nerve of schwannoma before operation, we report our experience.
PMID- 17040057
TI - [Bladder cancer with skin metastasis: a case report].
AB - Bladder carcinoma with skin metastasis is extremely rare. We herein report a case
of a bladder tumor with skin metastasis. A 68-year-old man was referred to our
hospital with macroscopic hematuria. Cystoscopy revealed a trigone papillary
tumor. Transurethral resection of bladder tumor (TURBT) was performed and the
pathological diagnosis was transitional cell carcinoma (TCC), pT1, G3.
Thereafter, he received several courses of TURBT, intravesical chemotherapy
(pirarubicin, bacillus Calmette-Guerin and mitomycin C) and intra-arterial
chemotherapy because of recurrence. Thirteen years later, he underwent total
cystoprostatectomy with neobladder formation. Histological examination revealed
muscle-invasive bladder cancer with a staging of T3bNOM0. Two years and three
months later, multiple firm nodules with eruptions appeared on the skin in
several regions; they were resected and the histological findings revealed TCC.
This indicated metastatic spread from the primary bladder TCC. He received only
supportive treatment during this period due to renal dysfunction. He died four
months after the manifestation of the skin metastasis due to multiple metastases.
PMID- 17040058
TI - [A case of transitional cell carcinoma with squamous differentiation which
developed squamous cell carcinoma in situ in the clinical course].
AB - In August 2000, a 62-year-old woman presented to another municipal hospital with
macroscopic Transurethral resection of bladder tumor (TUR-Bt) was performed. The
pathological hematuria. diagnosis was transitional cell carcinoma (TCC), G2 >
squamous cell carcinoma (SCC). TUR-Bt repeated in July 2003 indicated recurrence.
The pathological diagnosis was TCC, G2. She was referred to our hospital in
August 2003 because she desired bladder preservation. After cystoscopy and random
biopsy, pathological diagnosis was TCC with squamous differentiation, G1-G2,
pTis. She received 7 weekly intravesical bacillus Calmette-Guerin (BCG)
instillations. In April 2004, TUR-Bt was repeated and multiple recurrences were
found. The pathological diagnosis was TCC with squamous differentiation, G1-G2,
pTa. She received 10 weekly intravesical Pirarubicin hydrochroride instillations.
In August cystoscopy and random biopsy were performed for evaluation of the
intavesical instillation treatment. Pathological diagnosis was atypical squamous
cells. In November, cystoscopy revealed recurrence of a bladder tumor. After
admission, a small papillary tumor and multiple flat lesion biopsies demonstrated
SCC without obvious invasion. The patient underwent cystectomy. There were
widespread areas of full thickness squamous atypia. Most of the bladder did not
show appearance of typical TCC, but the final pathological diagnosis was TCC
because the case developed from TCC and could not be diagnosed as pure SCC. The
diagnosis of SCC in situ of bladder is difficult, and this may contribute to its
rarity.
PMID- 17040059
TI - [Small cell carcinoma of the prostate: a case report].
AB - A 79-year-old man was admitted to our department with a chief complaint of
urinary incontinence. The prostate was enlarged (145 cc), although the serum
level of prostate specific antigen (PSA) was within the normal range (1.09
ng/ml). Digital rectal examination showed an enlarged, irregular prostate with
stony hardness. We performed a prostate biopsy and histological examinations
indicated poorly differentiated adenocarcinoma with a Gleason score of 5+5=10. A
computed tomographic (CT) scan revealed a prostatic tumor invading the bladder,
seminal vesicle and rectum. He was diagnosed with a stage T4N1M0 adenocarcinoma
of the prostate. He was started-on hormonal therapy, but died one month from the
start of treatment. Histological and immunohistological examinations were
repeated; suggesting small cell neuroendocrine carcinoma of the prostate.
PMID- 17040060
TI - Acute myocardial infarction during combined chemotherapy with bleomycin,
etoposide and cisplatin for testicular cancer.
AB - We report a case of acute myocardial infarction during combined chemotherapy with
bleomycin, etoposide and cisplatin for testicular cancer. A 30-year-old smoker
without any history of ischemic heart disease complained of sudden chest pain on
the ninth day of his third course of chemotherapy. An electrocardiogram showed ST
segment elevation in II, III and aVF. Emergency coronary angiography revealed
total occlusion of the right coronary artery by a thrombus, which was removed by
coronary atherectomy.
PMID- 17040061
TI - [A case of myxoid liposarcoma in the right inguinal region: a case report].
AB - We report a case of myxoid liposarcoma developed in the right inguinal region. A
45-year-old man visited our hospital with a chief complaint of painless right
inguinal mass. He was diagnosed with right direct inguinal hernia for the first
time and received a hernia repair. However, the size of the inguinal mass
increased gradually after the operation. Then, the tumor was re-evaluated by
imaging study such as ultrasonography, computed tomography and magnetic resonance
imaging. A fatty mass 4.0 cm in diameter was demonstrated and the tumor was
diagnosed as a liposarcoma preoperatively. In addition to the right high
orchiectomy, surrounding fatty tissue was also removed at the time of the
operation. Histological examination revealed a myxoid liposarcoma and the
existence of several daughter regions outside the pseudo-capsule. Right spermatic
cord and testis were intact. Postoperatively, he received 54 Gy dose of radiation
therapy to right inguinal region for the prevention of the local recurrence of
the disease.
PMID- 17040062
TI - [A case of metastatic tumor of spermatic cord from ascending colon carcinoma].
AB - A 75-year-old man presented with a left inguinal mass two months after surgery
for ascending colon cancer. Physical examination revealed a solid mass in the
left inguinal area. High orchiectomy was performed under the diagnosis of
spermatic cord tumor. Gross examination of the specimen revealed a 5.0 X 3.2 X
3.0 cm tumor in the spermatic cord. Pathological examination of the tumor was
reported as poorly differentiated adenocarcinoma with features similar to those
of previously resected colon cancer. He developed peritonitis carcinomatosa and
died 6 months after left orchiectomy. To our knowledge, a metastatic tumor of the
spermatic cord from colon or rectal cancer is rare. As previously reported, the
prognosis of this case was also poor.
PMID- 17040064
TI - [Arterial injury associated with tension-free vaginal tape procedure successfully
treated by radiological embolization: a case report].
AB - A 75-year-old woman underwent a tension-free vaginal tape (TVT) procedure for
urinary stress incontinence. The patient complained of lower abdominal pain, a
feeling of lower abdominal distension and nausea three hours after the operation.
In addition, systolic blood pressure decreased gradually to 80 mmHg. Enhanced
computed tomography revealed a retropubic hematoma sized up to 16 cm X 12 cm X 11
cm and bleeding from a vessel running through the posterosuperior aspect of the
pubic bone. Successively, arteriography was performed. The arteriogram also
confirmed arterial injury, which was successfully treated by selective
embolization using a gelatin sponge and pushable coils. Postoperative course was
uneventful requiring neither blood transfusion nor surgical removal of the
hematoma.
PMID- 17040063
TI - [A case of leiomyosarcoma of the scrotum: chemotherapy with anti-cancer agents
was effective for the lung metastasis].
AB - A 59-year-old male was referred to our hospital with the chief complaint of a
painless scrotal mass. A 6 X 4.5 X 4 cm elastic hard mass with irregular surface
was palpable in the right scrotum. We diagnosed a tumor in the right scrotum and
resected the tumor surgically. Histopathologically, the tumor was liposarcoma of
the right scrotum. Lung tumors were found 20 months after resection of the
origin. Systemic chemotherapy with new anti-cancer agents (Paclitaxel and
Gemcitabine) was performed. The main tumor was reduced to 56% in its diameter
after 6 courses of chemotherapy. Exclusion of the right middle and lower
pulmonary lobe was performed. The final pathological diagnosis of the lung tumor
was metastatic liposarcoma.
PMID- 17040065
TI - Growth and sporulation of Phytophthora ramorum in vitro in response to
temperature and light.
AB - Phytophthora ramorum, recently found in the US, is causing concern for hardwood
forests and the nursery industry. In an effort to identify some of the
environmental limitations to growth and sporulation we undertook a laboratory
study of four US and three European (EU) isolates. On V8 media, isolates grew
when incubated at 2-28 C and produced chlamydospores at 8-28 C. Sporangia were
produced at all temperatures tested: 10-30 C for US isolates and 6-26 C for EU
isolates. Optimal temperatures were 16-26 C for growth, 14-26 C for chlamydospore
production and 16-22 C for sporangia production. US isolates grew less and
produced fewer spores when exposed to increasing doses of near-UV radiation (50
300 microW/cm(2)) and visible radiation (250-1500 microW/cm(2)). EU isolates were
exposed to 300 microW/cm(2) near-UV only, which significantly reduced growth of
one of three isolates and had no significant effect on spore production. In our
studies P. ramorum tolerated a broad range of temperature and light conditions,
which suggests that it is capable of establishment in a wide geographic area.
PMID- 17040066
TI - Spatial structure and richness of ectomycorrhizal fungi colonizing bioassay
seedlings from resistant propagules in a Sierra Nevada forest: comparisons using
two hosts that exhibit different seedling establishment patterns.
AB - In this study we analyzed the spatial structure of ectomycorrhizal fungi present
in the soils as resistant propagules (e.g. spores or sclerotia) in a mixed
conifer forest in the Sierra Nevada, California. Soils were collected under old
growth Abies spp. stands across approximately 1 km and bioassayed with seedlings
of hosts that establish best in stronger light (Pinus jeffreyi) or that are shade
tolerant (Abies concolor). Ectomycorrhizal fungi colonizing the roots were
characterized with molecular techniques (ITSRFLP and DNA sequence analysis).
Wilcoxina, five Rhizopogon species and Cenococcum were the most frequent of 17
detected species. No spatial structure was detected in the resistant propagule
community as a whole, but P. jeffreyi seedlings had higher species richness and
associated with seven Rhizopogon species that were not detected on A. concolor
seedlings. We drew two conclusions from comparisons between this study and a
prior study of the ectomycorrhizal community on mature trees in the same forest:
(i) the resistant propagule community was considerably simpler and more
homogeneous than the active resident community across the forest and (ii)
Cenococcum and Wilcoxina species are abundant in both communities.
PMID- 17040067
TI - Comparison of taxonomic, colony morphotype and PCR-RFLP methods to characterize
microfungal diversity.
AB - We compared three methods for estimating fungal species diversity in soil
samples. A rapid screening method based on gross colony morphological features
and color reference standards was compared with traditional fungal taxonomic
methods and PCR-RFLP for estimation of ecological indices of soil microfungal
community composition. Normalized counts of colony morphotypes on dichloran rose
bengal medium were used to estimate species richness (S) and evenness (J) and to
calculate Shannon's diversity (H) and Simpson's (SI) dominance indices. Isolates
were obtained by dilution plating techniques from litter and soil layer samples
taken from Douglas-fir forest and clear-cut areas at two locations in the Cascade
Mountains. The highest correspondence (97%) was observed between taxonomic
identification and RFLP patterns (32:33). Cladistic analyses of PCR-RFLP patterns
indicated an 81% correspondence between RFLP patterns:colony morphotypes (33:41).
A correspondence of 78% was observed between traditional taxonomic
identification:colony morphotypes (32:41). Statistical analyses of ecological
indices based on quantitative application of the colony morphotyping method
indicated significant differences (P < 0.05) in fungal community composition
between forested and clear-cut areas at the Toad Road site but not at the Falls
Creek site. Comparisons of ecological indices based on traditional identification
of taxa by microscopic characterization on defined culture media resulted in
identical findings of statistical significance. The colony morphotyping approach
is proposed as a screening method to identify potential effects of land
management practices, edaphic factors and pollutants on microfungal diversity.
PMID- 17040068
TI - 5-fluoro-orotic acid induces chromosome alterations in genetically manipulated
strains of Candida albicans.
AB - We previously reported the occurrence of chromosome alterations in a Candida
albicans prototrophic strain 3153A treated with 5-fluoro-orotic acid (5-FOA). In
this study we investigated the mutagenic properties of 5-FOA with two derivatives
of C. albicans strain CAF4-2 (ura3/ura3), each containing an ectopic copy of URA3
gene (ura3/ ura3 URA3) on a different chromosome. As expected, after the
ura3/ura3 URA3 constructs were applied to 5-FOA containing solid medium, the "pop
outs" that lost URA3 appeared. However most of the "pop-outs" acquired various
chromosome alterations. Thus constructs exposed to 5-FOA should be examined for
chromosome alterations or the use of 5-FOA should be avoided.
PMID- 17040069
TI - Isolation of cell wall mutants in Aspergillus nidulans by screening for
hypersensitivity to Calcofluor White.
AB - As a first step toward identifying novel genes of wall metabolism in filamentous
fungi, we have screened a collection of Aspergillus nidulans mutants for strains
exhibiting hypersensitivity toward the chitin binding agent Calcofluor White
(CFW). This strategy has been used previously to identify cell wall mutants in
Saccharomyces cerevisiae. We have identified 10 mutants representing eight loci,
designated calA through calH, for Calcofluor hypersensitivity. All cal mutants
are impaired for sporulation at 30 C or 42 C or both, and in eight of the 10
mutations this sporulation defect shows at least partial osmotic remediability.
All cal mutants show elevated sensitivity to one or more of the following agents:
Caspofungin, Nikkomycin, Tunicamycin, Congo red and SDS, which are recognized
wall-compromising agents or have been shown to be inhibitory to wall integrity
mutants in yeast. Seven of the 10 cal mutants show swelling at elevated
temperature, which in most cases is osmotically remediable. Spore swelling also
can be induced at 30 C in all but one of the cal mutants by germination in the
presence of one or more of the following: Caspofungin, Nikkomycin or Tunicamycin.
Analysis of wall sugars showed no major changes in mutant strains. We also report
that the chitin synthase inhibitor Nikkomycin induces excessive spore swelling
during germination in all tested strains that have wild type cell wall metabolism
(GR5, A4, A28 and AH12) at 42 C but not at 30 C. This effect mimics that of
certain temperature-sensitive swollen cell (swo) mutations.
PMID- 17040071
TI - Three new Lasiodiplodia spp. from the tropics, recognized based on DNA sequence
comparisons and morphology.
AB - Botryosphaeria rhodina (anamorph Lasiodiplodia theobromae) is a common endophyte
and opportunistic pathogen on more than 500 tree species in the tropics and
subtropics. During routine disease surveys of plantations in Australia and
Venezuela several isolates differing from L. theobromae were identified and
subsequently characterized based upon morphology and ITS and EF1-alpha nucleotide
sequences. These isolates grouped into three strongly supported clades related to
but different from the known taxa, B. rhodina and L. gonubiensis, These have been
described here as three new species L. venezuelensis sp. nov., L. crassispora sp.
nov. and L. rubropurpurea sp. nov. The three could be distinguished easily from
each other and the two described species of Lasiodiplodia, thus confirming
phylogenetic separations. Furthermore all five Lasiodiplodia spp. now recognized
separated from Diplodia spp. and Dothiorella spp. with 100% bootstrap support.
PMID- 17040070
TI - Phylogenetic relationships of Pythium and Phytophthora species based on ITS rDNA,
cytochrome oxidase II and beta-tubulin gene sequences.
AB - Fifty-eight isolates representing 39 Pythium species and 17 isolates representing
nine Phytophthora species were chosen to investigate intra- and intergeneric
relationships with sequence analysis of three genomic areas. The internal
transcribed spacer regions (ITS1 and ITS2), including the 5.8S gene of the
ribosomal DNA were PCR amplified with the universal primers ITS1 and ITS4. On the
other hand 563 bp of the cytochrome oxidase II (cox II) gene was amplified with
the primer pair FM66 and FM58 for Pythium and FM75 and FM78 for Phytophthora. The
658 bp partial beta-tubulin gene was amplified with the forward primer BT5 and
reverse primer BT6. Maximum parsimony analysis of the three DNA regions revealed
four major clades, reflective of sporangial morphology. Clade 1 was composed of
Pythium isolates that bear filamentous to lobulate sporangia. Clade 2 represents
Pythium isolates that bear globose to spherical zoosporangia or spherical hyphal
swellings. Meanwhile Phytophthora isolates were lumped into Clade 3 wherein the
papillate, semipapillate and nonpapillate species occupied separate subclades.
Lastly, Clade 4 was composed of Pythium species that bear subglobose sporangia
resembling the papillate sporangia observed in Phytophthora. Hence a number of
species (Ph. undulata, P. helicoides, P. ostracodes, P. oedochilum and P. vexans)
have been proposed to be the elusive intermediate species in the Pythium-to
Phytophthora evolutionary line.
PMID- 17040073
TI - Morphology and development of the reticuloperidial ascomata of Auxarthron
conjugatum.
AB - Light and electron microscopy showed that the reticuloperidium of thick-walled
hyphae, characteristic of the mature ascoma of Auxarthron conjugaturn, originated
from branches that grew from the broad, gyre-like hyphal loops making up the
ascomatal initials. Within the developing peridium, short, acropetally
proliferating chains of prototunicate asci each arose from a single crozier and
matured from base to tip. The walls of young asci were two-layered but evanesced
as they matured with the outer layer dissolving before the inner one. Distal asci
in some chains retained the inner wall, detached from adjacent asci by septum
schizolysis and when transferred to fresh media produced germ tubes and mycelium.
Ultraviolet epifluorescent staining with a DNA intercalator (Hoechst) indicated
that these spore-like asci probably contained diploid nuclei. In normal asci,
ascospores had an inner, electron lucent primary wall and a three-layered
secondary wall. The deposition pattern of the middle layer of the secondary wall
created the distinctive array of pits and ridges characteristic of the ascospores
in this taxon. The production of ascospores, spore-like asci and arthroconidia,
along with the tendency of ascospores to adhere in a mass, is interpreted as
contributing to the reproductive flexibility and inoculum potential of A.
conjugatum. In all respects the ascomata of A. conjugatum differed substantially
from the morphologically similar taxon, Myxotrichum arcticum. These findings
underscore the benefit of using DNA-based phylogenies in concert with cytological
and ultrastructural observations for exploring selective pressures behind
homoplasious characters and revealing novel structural features.
PMID- 17040072
TI - Multilocus sequence data reveal extensive phylogenetic species diversity within
the Neurospora discreta complex.
AB - Previous observations of morphological, reproductive and genetic variation have
suggested that Neurospora discreta, as presently circumscribed, might represent a
diverse complex of multiple species. To investigate this hypothesis we examined
the phylogenetic relationships among 73 fungal strains traditionally identified
as N. discreta. Strains were chosen from across the morphological, ecological and
geographical ranges of the species. Sequence data were obtained from three
unlinked nuclear loci, and phylogenetic species recognition was applied to the
dataset using protocols that have been shown to be reliable for identifying
independent lineages and delineating species of Neurospora. The results
demonstrate that the present circumscription of N. discreta includes at least
eight separate phylogenetic species. This research also reveals an abundance of
previously unrecognized genetic diversity within the genus, characterizes the
interspecific evolutionary relationships and contributes to a fuller
understanding of species diversity in Neurospora.
PMID- 17040074
TI - Gerronema wildpretii sp. nov. (Agaricales, Basidiomycetes) a new species from the
Canary Islands.
AB - Gerronema wildpretii, collected in climactic sites of the monteverde forest of
the Canary Islands is described and illustrated. Its macro- and microscopic
features delimit this taxon as a new species.
PMID- 17040075
TI - Vittatispora, a new melanosporaceous genus from Indian soil.
AB - Vittatispora coorgii gen. sp. nov., isolated from soil in India, is described and
illustrated. The fungus has morphological characteristics of the genera
Melanospora, Sphaerodes and Syspastospora. The most striking feature is the
presence of a thick hyaline ridge along the vertical axis of the lemon-shaped
ascospores wall. Perithecia also have a long neck composed of adhering hyphae,
similar to that of Syspatospora. Phylogenetic studies on the 28S rDNA indicate it
is closely related to Melanospora and Sphaerodes and belongs in the
Ceratostomataceae. The new genus is based on the distinctive morphology and
phylogenetic analyses. The fungus grew in culture only conjointly with a sterile
fungus which a BLAST analysis suggested was close to Tetracladium marchalianum.
PMID- 17040076
TI - Rediscovery of Alnicola cholea (Cortinariaceae): taxonomic revision and
description of its mycorrhiza with Polygonum viviparum (Polygonaceae).
AB - Alnicola cholea, a little-known species so far reported only from the two
original localities in the French Alps, is redefined here based on revision of
herbarium materials and studies of recent field collections. A detailed
morphological and anatomical description of fruit bodies of Alnicola cholea,
including a discussion on its taxonomic status and distribution data is provided.
Due to the unique combination of characters of Alnicola cholea within the genus,
a new monospecific section is introduced for this species: Alnicola sect. Cholea,
sect. nov. Mycorrhizal symbiosis of A. cholea with an arcticalpine plant
Polygonum viviparum was observed in the Tatra Mountains (Poland). A description
of these mycorrhizae is given, providing first detailed data on an identified
herbaceous plant mycorrhiza.
PMID- 17040077
TI - Trichomycetes from China and the description of three new Smittium species.
AB - Trichomycetes were recovered from the guts of aquatic insect larvae collected
from a stream in the Qinling Mountains in western China. These collections
included Smittium hecatei, known only from Spain, as well as Smittium simulii and
Stachylina penetralis, which appear to be more widely distributed. Caudomyces
japonicus, previously recorded only from Japan, also is reported from crane fly
larvae (Antocha sp.) from China. We describe three new species, Smittium
chinliense from a tipulid host, as well as Smittium naiadis and Smittium
nodifixum, both from chironomid larvae. A probable new species of Gauthieromyces
was collected in mayfly nymphs and is illustrated but not described here.
PMID- 17040078
TI - Anamorphic fungi from French Guyana: two undescribed Gliocephalotrichum species
(Nectriaceae, Hypocreales).
AB - Morphological and molecular studies of Gliocephalotrichum collections from rain
forest leaf litter in French Guyana revealed the occurrence of two undescribed
species, described here as G. bacillisporum and G. longibrachium. Both species
have a whorl of sterile stipe extensions directly subtending the conidiogenous
penicilli. Gliocephalotrichum bulbilium also was isolated from leaf litter in
French Guyana. Two sequences in GenBank, of uncultured ascomycetes from Gabon,
Africa, cluster in the Gliocephalotrichum clade, suggesting the probable
existence of additional undescribed taxa from the Central African rainforest.
PMID- 17040079
TI - Hypocrea crystalligena sp. nov., a common European species with a white-spored
Trichoderma anamorph.
AB - The new species Hypocrea crystalligena (Hypocreales, Ascomycota, Fungi) is
described as a holomorph and characterized based on an integrated phenotypic and
phylogenetic approach, using teleomorph and anamorph morphologies, culture
studies and analyses of phylogenetic markers including internal transcribed
spacer 1 and 2 (ITS1 and 2), two last introns of the translation elongation
factor 1-alpha encoding gene (tef1), and a portion of the rpb2 gene, encoding the
second largest RNA polymerase subunit. Stromata of H. crystalligena show
similarities with those of species from Trichoderma sect. Trichoderma but differ
in several respects, including color, presence of white crystals on the surface
and small ascospores. Colonies on CMD appear distinct, form colorless to white
crystals on isolation, a yellowish to brown pigment and an anamorph with hyaline
conidia exhibiting verticillium-like to gliocladium-like structural elements.
ITS1 and 2 sequences exhibit all genus-specific features but also contain several
unique hallmarks permitting development of a species-diagnostic barcode. Based on
the analyses of partial rpb2 and tef1 sequences, H. crystalligena constitutes a
separate evolutionary lineage with H. megalocitrina and H. psychrophila as its
nearest neighbors. All these species form one phylogenetic clade with the H.
pulvinata/H. citrina node.
PMID- 17040080
TI - A strategy for recovering high quality genomic DNA from a large number of
Phytophthora isolates.
AB - We present a strategy to recover high molecular weight genomic DNA from large
numbers of isolates of Phytophthora. Included are steps for generating mycelial
mass in 24-well reuseable deep well plates, efficient lyophilization and
disruption of the mycelium and genomic DNA extraction with 96-well glass fiber
filter plates. The resulting DNA is consistently high molecular weight and is
suitable for applications that require high quality DNA such as AFLP analysis and
TILLING. A single operator easily can manage mycelium preparation and/or DNA
extraction from 384 isolates in a single day and this approach might be useful
for other fungi or fungi-like organisms that can be grown in liquid media.
PMID- 17040081
TI - Editors' preface: reflexivity and responsiveness: the expansive orbit of
knowledge.
PMID- 17040082
TI - Mindblindness: autism, writing, and the problem of empathy.
PMID- 17040083
TI - Autism and the contemporary sentimental: fiction and the narrative fascination of
the present.
PMID- 17040084
TI - Listening to Chekhov: narrative approaches to depression.
PMID- 17040085
TI - Enlightening the fibre-woven body: William Blake and eighteenth-century fibre
medicine.
PMID- 17040086
TI - Writing against memory and forgetting.
PMID- 17040087
TI - Trauma, narrative, and two forms of death.
PMID- 17040088
TI - "Himself he devises too for company": self-making in Samuel Beckett's Company.
PMID- 17040089
TI - Medical-industrial Discourses: Muriel Rukeyser's "The Book of the Dead".
PMID- 17040090
TI - A Phase II Nonrandomised Open-Label Study of Liposomal Daunorubicin (DaunoXome)
in Advanced Soft Tissue Sarcoma.
AB - Thirty four patients with advanced soft tissue sarcoma not previously treated
with an anthracycline were treated with DaunoXome 100mg/m2 every 3 weeks. Thirty
three patients were evaluable for toxicity. Grade 3-4 neutropenia was seen in 20
patients (60.6%), complicated by febrile neutropenia in 2 (6.1%). Other grade 3
toxicities were rare. Among 32 patients assessable for response, one patient had
a partial response, giving a response rate of 3.13% (95% confidence interval,
0.08-16.22%). Seven patients (21.9%) had stable disease, and 24 patients (75.0%)
had disease progression. The median time to progression for all patients was 42
days (95% CI, 39-49) and the progression-free rate at 3 months was 12.5%. In
conclusion, DaunoXome at this dose and schedule is well tolerated in patients
with advanced soft tissue sarcoma, but is not associated with significant
activity. Further studies at this dose and schedule cannot be recommended in this
disease.
PMID- 17040091
TI - Relative hypocalcaemia and muscle cramps in patients receiving imatinib for
gastrointestinal stromal tumour.
AB - Purpose. Imatinib treatment causes muscle cramps in up to 40% of patients, but
their pathogenesis is unknown. We present a case series illustrating an
association between imatinib, relative hypocalcaemia, and the development of
cramps. Patients. The index patient developed muscle spasms and cramps after
receiving imatinib for gastrointestinal stromal tumour (GIST) for 5 months. The
adjusted serum calcium had dropped to the lower limit of normal. The low serum
calcium and muscle cramps improved on stopping imatinib and recurred on
rechallenge. We reviewed the medical records of 16 further patients. Results. Two
patients reported muscle cramps (12%). There was a rapid and sustained reduction
in adjusted serum calcium in the first 6 months from 2.45 +/- 0.11 mmol/L (mean
+/- SD) to 2.30 +/- 0.08 mmol/L (p = 0.025). Conclusion. Imatinib treatment of
GIST is associated with reduction in serum calcium which may explain the
development of neuromuscular symptoms. In patients receiving imatinib, serum
electrolytes should be monitored and muscle cramps treated by correction of serum
calcium, or an empirical trial of quinine sulphate.
PMID- 17040092
TI - The radiation response of sarcomas by histologic subtypes: a review with special
emphasis given to results achieved with razoxane.
AB - Purpose. Relatively few results are available in the literature about the
radiation response of unresectable sarcomas in relation to their histology.
Therefore, an attempt was made to summarize the present situation. Materials and
methods. This report is based on a review of the literature and the author's own
experience. Adult-type soft tissue sarcomas, chondrosarcomas, and chordomas were
analyzed. Radioresponse was mainly associated with the degree of tumor shrinkage,
that is, objective responses. Histopathologic responses, that is, the degree of
necrosis, are only discussed in relation to radiation treatment reports of soft
tissue sarcomas as a group. Results. Radiation therapy alone leads to major
responses in about 50% of lipo-, fibro-, leiomyo-, or chondrosarcomas. The
response rate is less than 50% in malignant fibrous histiocytomas, synovial,
neurogenic, and other rare soft tissue sarcomas. The response rates may increase
up to 75% through the addition of radiosensitizers such as halogenated
pyrimidines or razoxane, or by the use of high-LET irradiation. Angiosarcomas
become clearly more responsive if biologicals, angiomodulating, and/or tubulin
affinic substances are given together with radiation therapy. Razoxane is able to
increase the duration and quality of responses even in difficult-to-treat tumors
like chondrosarcomas or chordomas. Conclusions. The available data demonstrate
that the radioresponsiveness of sarcomas is very variable and dependent on
histology, kind of radiation, and various concomitantly given drugs. The rate of
complete sustained remissions by radiation therapy alone or in combination with
drugs is still far from satisfactory although progress has been made through the
use of sensitizing agents.
PMID- 17040093
TI - Clinical outcomes of intraoperative radiation therapy for extremity sarcomas.
AB - Purpose. Radiation of extremity lesions, a key component of limb-sparing therapy,
presents particular challenges, with significant risks of toxicities. We sought
to explore the efficacy of intraoperative radiation therapy (IORT) in the
treatment of soft tissue sarcomas of the extremities. Patients. Between 1995 and
2001, 17 patients received IORT for soft tissue sarcomas of the extremities.
Indications for IORT included recurrent tumors in a previously radiated field or
tumors adjacent to critical structures. Results. Gross total resections were
achieved in all 17 patients. Two patients experienced locoregional relapses, six
patients recurred at metastatic sites, and one patient died without recurrence.
Thirty-six month estimates for locoregional control, disease free survival, and
overall survival were 86%, 50%, and 78%, respectively. IORT was extremely well
tolerated, with no toxicities referable to IORT. Conclusions. For patients with
soft tissue sarcomas of the extremities, IORT used as a boost to EBRT provides
excellent local control, with limited acute toxicities.
PMID- 17040094
TI - Future of toxicology--predictive toxicology: An expanded view of "chemical
toxicity".
AB - A chemistry approach to predictive toxicology relies on structure-activity
relationship (SAR) modeling to predict biological activity from chemical
structure. Such approaches have proven capabilities when applied to well-defined
toxicity end points or regions of chemical space. These approaches are less well
suited, however, to the challenges of global toxicity prediction, i.e., to
predicting the potential toxicity of structurally diverse chemicals across a wide
range of end points of regulatory and pharmaceutical concern. New approaches that
have the potential to significantly improve capabilities in predictive toxicology
are elaborating the "activity" portion of the SAR paradigm. Recent advances in
two areas of endeavor are particularly promising. Toxicity data informatics
relies on standardized data schema, developed for particular areas of
toxicological study, to facilitate data integration and enable relational
exploration and mining of data across both historical and new areas of
toxicological investigation. Bioassay profiling refers to large-scale high
throughput screening approaches that use chemicals as probes to broadly
characterize biological response space, extending the concept of chemical
"properties" to the biological activity domain. The effective capture and
representation of legacy and new toxicity data into mineable form and the large
scale generation of new bioassay data in relation to chemical toxicity, both
employing chemical structure information to inform and integrate diverse
biological data, are opening exciting new horizons in predictive toxicology.
PMID- 17040095
TI - Fenton chemistry and iron chelation under physiologically relevant conditions:
Electrochemistry and kinetics.
AB - The goal of iron-chelation therapy is to reduce the levels of labile plasma iron,
and intravenously administered desferrioxamine is the gold standard of
therapeutic agents. Hydroxypyridinones, e.g., CP20 (3-hydroxy-1,2-dimethylpyridin
4(1H)-one), are used or are under investigation as orally administered iron
chelators. We determined electrode potentials of CP20, the related
hydoxypyridones CP361, CP363, and CP502, and ICL670 (4-[3,5-bis(2-hydroxyphenyl)
1H-1,2,4-triazol-1-yl]benzoic acid) under physiologically relevant conditions to
address the question of whether iron in the presence of these chelating agents
can carry out Fenton chemistry in vivo. We found that iron(III) but not iron(II)
binds tightly to both CP20 and ICL670 at pH 7 and higher, compared to nearly
complete binding of 1 microM iron(II) to 10 microM desferrioxamine at pH 7.4 The
electrode potentials of the hydroxypyridinones shift to more negative values with
decreasing pK(a) values at lower concentrations of iron(III) (0.02 mM) and ligand
(0.1 mM). The electrode potential of the iron-CP20 system decreases as a function
of increasing pH, with a minimum near pH 10.5. We estimate an electrode potential
for the ascorbyl radical/ascorbate couple under physiological conditions of +105
mV, which is higher than the electrode potential of the iron(III) complex of CP20
at all concentrations of iron. The rate of oxidation of iron(II) in the presence
of CP20 by hydrogen peroxide increases with the concentrations of both ligand and
peroxide. Although iron(II) is oxidized by hydrogen peroxide, the thus-formed
Fe(III)(CP20)(3) complex cannot be reduced by ascorbate. Therefore, the tight
binding of iron(III) by this class of chelators prevents redox cycling.
PMID- 17040096
TI - Identification of potential genomic biomarkers of hepatotoxicity caused by
reactive metabolites of N-methylformamide: Application of stable isotope labeled
compounds in toxicogenomic studies.
AB - The inability to predict if a metabolically bioactivated compound will cause
toxicity in later stages of drug development or post-marketing is of serious
concern. One approach for improving the predictive success of compound toxicity
has been to compare the gene expression profile in preclinical models dosed with
novel compounds to a gene expression database generated from compounds with known
toxicity. While this guilt-by-association approach can be useful, it is often
difficult to elucidate gene expression changes that may be related to the
generation of reactive metabolites. In an effort to address this issue, we
compared the gene expression profiles obtained from animals treated with a soft
electrophile-producing hepatotoxic compound against corresponding deuterium
labeled analogues resistant to metabolic processing. Our aim was to identify a
subset of potential biomarker genes for hepatotoxicity caused by soft
electrophile-producing compounds. The current study utilized a known hepatotoxic
compound N-methylformamide (NMF) and its two analogues labeled with deuterium at
different positions to block metabolic oxidation at the formyl (d(1)) and methyl
(d(3)) moieties. Groups of mice were dosed with each compound, and their livers
were harvested at different time intervals. RNA was prepared and analyzed on
Affymetrix GeneChip arrays. RNA transcripts showing statistically significant
changes were identified, and selected changes were confirmed using TaqMan RT-PCR.
Serum clinical chemistry and histopathologic evaluations were performed on
selected samples as well. The data set generated from the different groups of
animals enabled us to determine which gene expression changes were attributed to
the bioactivating pathway. We were able to selectively modulate the metabolism of
NMF by labeling various positions of the molecule with a stable isotope, allowing
us to monitor gene changes specifically due to a particular metabolic pathway.
Two groups of genes were identified, which were associated with the metabolism of
a certain part of the NMF molecule. The metabolic pathway leading to the
production of reactive methyl isocyanate resulted in distinct expression patterns
that correlated with histopathologic findings. There was a clear correlation
between the expression of certain genes involved in the cell cycle/apoptosis and
inflammatory pathways and the presence of reactive metabolite. These genes may
serve as potential genomic biomarkers of hepatotoxicity induced by soft
electrophile-producing compounds. However, the robustness of these potential
genomic biomarkers will need to be validated using other hepatotoxicants (both
soft- and hard-electrophile-producing agents) and compounds known to cause
idiosyncratic liver toxicity before being adopted into the drug discovery
screening process.
PMID- 17040097
TI - Identification and characterization of genes susceptible to transcriptional cross
talk between the hypoxia and dioxin signaling cascades.
AB - The aryl hydrocarbon receptor (AHR) and hypoxia inducible factors (HIFs) are
transcription factors that control the adaptive response to toxicants such as
dioxins and decreases in available oxygen, respectively. The AHR and HIFs utilize
the same heterodimeric partner, the aryl hydrocarbon nuclear translocator (ARNT)
for proper function. This requirement raises the possibility that cross-talk
exists between these critical signaling systems. Single gene and reporter assays
have yielded conflicting results regarding the nature of the competition for
ARNT. Therefore, to determine the extent of cross-talk between the AHR and HIFs,
a comprehensive analysis was performed using global gene expression analysis. The
results identified 767 and 430 transcripts that are sensitive to cobalt chloride
and 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD) stimulation, respectively, with
308 and 176, respectively, exhibiting sensitivity to cross-talk. The overlap
between these two sets consists of 33 unique transcripts, including the classic
target genes CYP1A1, carbonic anhydrase IX, and those involved in lipid
metabolism and coagulation. Computational analysis of the regulatory region of
these genes identified complex relationships between HIFs, AHR, and their
respective response elements as well as other DNA motifs, including the SRF, Sp
1, NF-kB, and AP-2 binding sites. These results suggest that HIF-AHR cross-talk
is limited to genes with regulatory regions that contain specific motifs and
architectures.
PMID- 17040098
TI - Synthesis and cytotoxic profile of 3,4-methylenedioxymethamphetamine ("ecstasy")
and its metabolites on undifferentiated PC12 cells: A putative structure-toxicity
relationship.
AB - The toxicological and redox profiles of MDMA and its major metabolites (MDA,
alpha-methyldopamine, N-methyl-alpha-methyldopamine, 6-hydroxy-alpha
methyldopamine, 3-methoxy-alpha-methyldopamine) were studied to establish a
structure-toxicity relationship and determine their individual contribution to
cell death induction by apoptosis and/or necrosis. The results of the comparative
toxicity study, using undifferentiated PC12 cells, strongly suggest that the
metabolites possessing a catecholic group are more toxic to the cells than MDMA
and metabolites with at least one protected phenolic group. Redox studies reveal
that an oxidative mechanism seems to play an important role in metabolite
cytotoxicity. Nuclear features of apoptosis and/or necrosis show that most of the
metabolites, particularly N-methyl-alpha-methyldopamine, induce cell death by
apoptosis, largely accompanied by necrotic features. No significant differences
were found between MDMA and the metabolites, concerning overall characteristics
of cell death. These results may be useful to ascertain the contribution of
metabolism in MDMA neurotoxicity molecular mechanisms.
PMID- 17040099
TI - Esterification prevents induction of the mitochondrial permeability transition by
N-acetyl perfluorooctane sulfonamides.
AB - N-Alkyl perfluorooctane sulfonamides have been widely used as surfactants on
fabrics and papers, fire retardants, and anticorrosion agents, among many other
commercial applications. The broad use, global distribution, and environmental
persistence of these compounds has generated considerable interest regarding
potentially toxic effects. We have previously reported that
perfluorooctanesulfonamidoacetate (FOSAA) and N
ethylperfluorooctanesulfonamidoacetate (N-EtFOSAA) induce the mitochondrial
permeability transition (MPT) in vitro, resulting in cytochrome c release,
inhibition of respiration, and generation of reactive oxygen species. By
synthesizing the corresponding methyl esters of FOSAA and N-EtFOSAA (methyl
perlfuorinated sulfonamide acetates), we tested the hypothesis that the N-acetate
moiety of FOSAA and N-EtFOSAA is the functional group responsible for induction
of the MPT. Swelling of freshly isolated liver mitochondria from Sprague-Dawley
rats was monitored spectrophotometrically and membrane potential (DeltaPsi) was
measured using a tetraphenylphosphonium-selective (TPP(+)) electrode. In the
presence of calcium, 40 microM FOSAA and 7 microM N-EtFOSAA each induced
mitochondrial swelling and a biphasic depolarization of membrane potential.
Mitochondrial swelling and the second-phase depolarization were inhibited by
cyclosporin-A or the catalyst of K(+)/H(+) exchange nigericin, whereas the first
phase depolarization was not affected by either. In contrast, the methyl esters
of FOSAA and N-EtFOSAA exhibited no depolarizing or MPT inducing activity.
Results of this investigation demonstrate that the carboxylic acid moiety of the
N-acetates is the active functional group, which triggers the MPT by
perfluorinated sulfonamides.
PMID- 17040100
TI - Computational prediction of the chromosome-damaging potential of chemicals.
AB - We report on the generation of computer-based models for the prediction of the
chromosome-damaging potential of chemicals as assessed in the in vitro chromosome
aberration (CA) test. On the basis of publicly available CA-test results of more
than 650 chemical substances, half of which are drug-like compounds, we generated
two different computational models. The first model was realized using the (Q)SAR
tool MCASE. Results obtained with this model indicate a limited performance (53%)
for the assessment of a chromosome-damaging potential (sensitivity), whereas CA
test negative compounds were correctly predicted with a specificity of 75%. The
low sensitivity of this model might be explained by the fact that the underlying
2D-structural descriptors only describe part of the molecular mechanism leading
to the induction of chromosome aberrations, that is, direct drug-DNA
interactions. The second model was constructed with a more sophisticated machine
learning approach and generated a classification model based on 14 molecular
descriptors, which were obtained after feature selection. The performance of this
model was superior to the MCASE model, primarily because of an improved
sensitivity, suggesting that the more complex molecular descriptors in
combination with statistical learning approaches are better suited to model the
complex nature of mechanisms leading to a positive effect in the CA-test. An
analysis of misclassified pharmaceuticals by this model showed that a large part
of the false-negative predicted compounds were uniquely positive in the CA-test
but lacked a genotoxic potential in other mutagenicity tests of the regulatory
testing battery, suggesting that biologically nonsignificant mechanisms could be
responsible for the observed positive CA-test result. Since such mechanisms are
not amenable to modeling approaches it is suggested that a positive prediction
made by the model reflects a biologically significant genotoxic potential. An
integration of the machine-learning model as a screening tool in early discovery
phases of drug development is proposed.
PMID- 17040101
TI - Metabolism of furans in vitro: ipomeanine and 4-ipomeanol.
AB - Ipomeanine (IPN), 4-ipomeanol (4-IPO), 1-ipomeanol (1-IPO), and 1,4-ipomeadiol
(DIOL) are toxic 3-substituted furans found in mold-damaged sweet potatoes. IPN
and 4-IPO are the most toxic, but all produce pulmonary toxicity in cattle and
rodents, and 4-IPO induces hepatotoxicity in humans. These furans require
metabolic activation to elicit toxicity, but the limited information obtained
from previous metabolism studies prompted us to initiate the investigation
reported here. Our initial studies of 4-IPO metabolism by rat liver microsomes
demonstrated that the oxidation of 4-IPO to IPN and reduction to DIOL occurred
and that more IPN was metabolized to a reactive species than 4-IPO or DIOL.
Incubation of IPN and Gly produced a 2'-pyrrolin-5'-one adduct establishing that
IPN was metabolized to an enedial. N-Acetylcysteine reacted with the 5'-aldehyde
of the enedial to give two 2',5'-dihydro-2'-hydroxyfurans stabilized by H bonding
between the 2'-OH and 3'-keto group. Reaction of the enedial metabolite of IPN
with one GSH gave several adducts including a pyrrole derived from the 1,2
addition of GSH to the 5'-aldehyde as well as two tricyclic 2'-pyrrolines derived
from the 1,4-addition of GSH at the 4'-position. The identities of the pyrrole
and 2'-pyrroline GSH adducts were confirmed by observation of structurally
similar adducts from Cys conjugation with the enedial metabolite of IPN. Several
minor adducts from the conjugation of the enedial metabolite of IPN with two GSH
were also detected. Mono-GSH and bis-GSH adducts were derived from both the 1,2
and 1,4-addition of GSH to the enedial metabolite of 4-IPO in rat liver
microsomal incubations of 4-IPO and GSH. Sequential oxidation of 4-IPO to IPN and
then to the enedial metabolite followed by GSH conjugation also occurred in the 4
IPO incubations. The complex structures of the reaction products of the enedial
with biological nucleophiles may explain why the many attempts to identify 4-IPO
adducts to protein have not been successful.
PMID- 17040102
TI - Characterization of the amino acid adducts of the enedial derivative of teucrin
A.
AB - The toxicity of germander, a herb used to treat obesity, is attributed to
cytochrome P450 activation of the furan ring of its major diterpenoid component
(teucrin A) into a reactive metabolite capable of adducting proteins. 1,4
Enedials have been proposed to be the reactive products of metabolism, possibly
arising from a rearrangement of putative epoxide intermediates. We synthesized
the enedial derivative of teucrin A as well as the enedial derived from a model
furan, 3-(4-methoxy-benzyloxymethyl)-furan, by dimethyldioxirane oxidation and
characterized the products of their reactions with amino acids and peptides. The
reactions of the model enedial, 2-(4-methoxy-benzyloxymethyl)-but-2-enedial, with
N-acetyl lysine (NAL) afforded regioisomeric N-alkyl-3-pyrrolin-2-ones, differing
in the substitution on the double bond of the heterocyclic ring. Novel products
formed in the reactions of the model enedial with N-acetyl cysteine (NAC) and
both NAC/NAL uncovered the existence of tautomerization between the enedial and a
hydroxyenal, which was manifest by the loss of 4-methoxybenzylalcohol and the
incorporation of a second molecule of NAC. The reactions of teucrin A-enedial
with NAC and NAL afforded analogues of the products observed with the model
enedial, and the existence of the tautomeric equilibrium resulted in
epimerization of the proton (H12) adjacent to the former furan ring. This work
further illuminates the complex chemical behavior of unsaturated dialdehydes as
an important class of toxic metabolites and lays the foundation for studies of
the protein targets of teucrin A-enedial.
PMID- 17040103
TI - Metabolism-dependent mutagenicity of a compound containing a piperazinyl indazole
motif: Role of a novel p450-mediated metabolic reaction involving a putative
oxaziridine intermediate.
AB - Compound 1a (6-chloro-5-{3-[4-(1H-indazol-3-yl)-piperazin-1-yl]-propyl}-3,3
dimethyl-1,3-dihydro-indol-2-one) was mutagenic to Salmonella typhimurium TA98 in
the presence of rat liver S9 subcellular fraction. The metabolism of 1a in rat
liver S9 or microsomes demonstrated that it underwent a P450-mediated N
deindazolation (loss of indazole ring) as a predominant metabolic pathway. To
investigate a possible link between metabolism and mutagenicity, a structural
analogue 1b (6-chloro-5-{3-[4-(1H-indazol-3-yl)-piperidin-1-yl]-propyl}-3,3
dimethyl-1,3-dihydro-indol-2-one), the cleaved product 2a (6-chloro-3,3-dimethyl
5-(3-piperazin-1-yl-propyl)-1,3-dihydro-indol-2-one), and the core motif 3a (3
piperazinyl indazole) were evaluated in the Ames assay. It was found that 1b was
not mutagenic to Salmonella typhimurium TA98 in the absence or presence of a
metabolic activating system. In contrast to 1a, 1b did not undergo the metabolic
cleavage (loss of indazole ring). Marginal mutagenicity of 2a to TA98 was
observed with rat liver S9, whereas 3a was shown to be a promutagen. It was
further demonstrated that 1a inactivated P450 3A, the principle enzyme catalyzing
the N-deindazolation reaction, in an NADPH-, time-, and concentration-dependent
manner. The kinetics of inactivation was characterized by a K(I) of 8.1 microM
and k(inact) of 0.114 min(-1). The differences in mutagenicity between 1a and 1b
suggest that a chemical bond extending from the 3-position of the indazole to a
heteroatom (as part of another cyclic ring) is a prerequisite for the toxicity.
The metabolic process leading to the elimination of the indazole from the rest of
the molecule apparently plays a key role in causing mutagenicity. It is
postulated that the N-deindazolation of 1a proceeds via an oxaziridine
intermediate, the formation of which is indirectly inferred from the presence of
benzoic acid in microsomal incubations. Benzoic acid is thought to be derived
from the hydrolysis of 3-indazolone, an unstable product generated from the
oxaziridine. Evidence suggests that the electrophilic oxaziridine intermediate
may be responsible for the mutagenicity and inactivation of P450 3A.
PMID- 17040104
TI - Enhanced sensitivity of Escherichia coli uvrB mutants to mitomycin C points to a
UV-C distinct repair for DNA adducts.
AB - Nucleotide excision repair (NER) in Escherichia coli repairs DNA by incising the
damaged strand on the 3' and 5' sides of the lesion within pyrimidine dimers and
DNA cross-linking adducts. Cross-linking adducts belong to a class of chemical
damage to DNA that prevent strand separation, and thus, replication and
transcription. For this reason, cross-linking agents such as mitomycin C (MC)
have been used in cancer chemotherapy. The mechanisms involved in MC binding to
DNA have already been defined; however, the repair of these lesions is not fully
understood. Our goal was to study the repair of MC DNA lesions in E. coli cells.
Several bacterial strains with specific mutations were tested for cellular
inactivation and kinetics of DNA repair through analysis of DNA sedimentation
profiles in alkaline sucrose gradients. The results obtained show that uvrB
mutants are extremely sensitive to MC in contrast to the other isogenic uvrA and
uvrC mutant strains. uvrB mutant strains are unable to repair DNA strand breaks
produced by MC. Thus, UvrB might play a NER-uncoupled role in the repair of
lesions induced by MC in vivo, different from its role on the repair of lesions
produced by UV-C. Also it is suggested that a modified NER system is taking place
in the repair of MC-adducts.
PMID- 17040105
TI - Nuclear magnetic resonance studies of the 4R and 4S diastereomers of
spiroiminodihydantoin 2'-deoxyribonucleosides: absolute configuration and
conformational features.
AB - The present study was aimed at gaining further insights into stereochemical and
conformational features of the 4R and 4S diastereomers of spiroiminodihydantoin
2'-deoxyribonucleosides that have been shown to be the predominant singlet oxygen
oxidation products of 2'-deoxyguanosine in aqueous solutions. It may be added
that spiroiminodihydantoin derivatives are efficiently generated by one-electron
and singlet oxygen oxidation of the 8-oxo-7,8-dihydroguanine moiety of several
nucleic acid components including nucleosides, nucleotides, and oligonucleotides.
The reported structural data on the pair of diastereomeric spiroiminodihydantoin
2'-deoxyribonucleosides 1 and 2 are mostly inferred from extensive (1)H and (13)C
NMR analyses including two-dimensional nuclear Overhauser effect measurements
performed in both D(2)O and dimethyl sulfoxide. This approach that has been shown
previously to be suitable to assign the stereochemistry of the base moiety of
oxidized pyrimidine nucleosides was completed by molecular modeling and quantum
mechanics studies. Thus, application of these two complementary approaches
together with the consideration of the results of a recent relevant quantum
mechanic study has allowed the assignment of the absolute stereoconfiguration of
the C-4 carbon of diastereomers 1 and 2. In addition, information is provided on
the conformational features of the 2-deoxyribose moiety and the orientation of
the base around the N-glycosidic bond of both 2'-deoxyribonucleosides 1 and 2.
PMID- 17040107
TI - Increased DNA damage in ALDH2-deficient alcoholics.
AB - Drinking alcohol is a risk factor for cancers of the oral cavity, pharynx,
larynx, and esophagus. Although many studies suggest that acetaldehyde, a major
metabolite of orally ingested alcohol, plays a crucial role in cancer initiation,
the link between the aldehyde dehydrogenase-2 (ALDH2) genotype and acetaldehyde
derived DNA damage has not yet been explored. We have developed a sensitive and
quantitative method for detecting the acetaldehyde-derived DNA adducts, N(2)
ethyl-2'-deoxyguanosine (N(2)-Et-dG), alpha-S- and alpha-R-methyl-gamma-hydroxy
1,N(2)-propano-2'-deoxyguanosine (alpha-S-Me-gamma-OH-PdG and alpha-R-Me-gamma-OH
PdG), and N(2)-(2,6-dimethyl-1,3-dioxan-4-yl)-deoxyguanosine (N(2)-Dio-dG), by
using liquid chromatography electrospray tandem mass spectrometry (LC/ESI-MS/MS)
and stable-isotope internal standards. We determined the DNA adducts in 44 blood
DNA samples from Japanese alcoholic patients. The levels of three acetaldehyde
derived DNA adducts, N(2)-Et-dG, alpha-S-Me-gamma-OH-PdG, and alpha-R-Me-gamma-OH
PdG, were significantly higher in alcoholics with the ALDH2 1/2 2 genotype
compared to those with the ALDH2 1/2 1 genotype. N(2)-Dio-dG was not detected in
any of the DNA samples analyzed. These results provide molecular evidence that
the ALDH2 genotype affects the genotoxic damage caused by acetaldehyde.
PMID- 17040106
TI - Reductive detoxification of arylhydroxylamine carcinogens by human NADH
cytochrome b5 reductase and cytochrome b5.
AB - Heterocyclic and aromatic amine carcinogens are thought to lead to tumor
initiation via the formation of DNA adducts, and bioactivation to
arylhydroxylamine metabolites is necessary for reactivity with DNA. Carcinogenic
arylhydroxylamine metabolites are cleared by a microsomal, NADH-dependent, oxygen
insensitive reduction pathway in humans, which may be a source of interindividual
variability in response to aromatic amine carcinogens. The purpose of this study
was to characterize the identity of this reduction pathway in human liver. On the
basis of our findings with structurally similar arylhydroxylamine metabolites of
therapeutic drugs, we hypothesized that the reductive detoxification of
arylhydroxylamine carcinogens was catalyzed by NADH cytochrome b5 reductase (b5R)
and cytochrome b5 (cyt b5). We found that reduction of the carcinogenic
hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette
smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b]
pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system
containing only human b5R and cyt b5. Specific activities were 56-346-fold higher
in the purified system as compared to human liver microsomes (HLM), with similar
Michaelis-Menten constants (K(m) values) in both systems. The stoichiometry for
b5R and cyt b5 that yielded the highest activity in the purified system was also
similar to that found in native HLM ( approximately 1:8 to 1:10). Polyclonal
antisera to either b5R or cyt b5 significantly inhibited N-hydroxy-4
aminobiphenyl (NHOH-4-ABP) reduction by 95 and 89%, respectively, and
immunoreactive cyt b5 protein content in individual HLM was significantly
correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH
PhIP). Finally, titration of HLM into the purified b5R/cyt b5 system did not
enhance the efficiency of reduction activity. We conclude that b5R and cyt b5 are
together solely capable of the reduction of arylhydroxylamine carcinogens, and we
further hypothesize that this pathway may be a source of individual variability
with respect to cancer susceptibility following 4-ABP or PhIP exposure.
PMID- 17040108
TI - Tyrosine-dependent oxidative DNA damage induced by carcinogenic
tetranitromethane.
AB - Tetranitromethane (TNM) is used as an oxidizer in rocket propellants and
explosives and as an additive to increase the cetane number of diesel fuel. TNM
was reported to induce pulmonary adenocarcinomas and squamous cell carcinomas in
mice and rats. However, the mechanisms underlying carcinogenesis induced by TNM
has not yet been clarified. We previously revealed that nitroTyr and nitroTyr
containing peptides caused Cu(II)-dependent DNA damage in the presence of P450
reductase, which is considered to yield nitroreduction. Since TNM is a reagent
for nitration of Tyr in proteins and peptides, we have hypothesized that TNM
treated Tyr and Tyr-containing peptides induce DNA damage by the modification of
Tyr. We examined DNA damage induced by TNM-treated amino acids or peptides using
(32)P-5'-end-labeled DNA fragments obtained from the human p53 tumor suppressor
gene and the c-Ha-ras-1 protooncogene. TNM-treated Tyr and Lys-Tyr-Lys induced
DNA damage including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in the
presence of Cu(II) and NADH. DNA damage was inhibited by catalase and
bathocuproine, indicating the involvement of H(2)O(2) and Cu(I). The cytosine
residue of the ACG sequence complementary to codon 273, well-known hotspots of
the p53 gene, was cleaved with piperidine and Fpg treatments. On the other hand,
nitroTyr and Lys-nitroTyr-Lys did not induce DNA damage in the presence of Cu(II)
and NADH. Time-of-flight mass spectrometry confirmed that reactions between Lys
Tyr-Lys and TNM yielded not only Lys-nitroTyr-Lys but also Lys-nitrosoTyr-Lys.
Therefore, it is speculated that the nitrosotyrosine residue can induce oxidative
DNA damage in the presence of Cu(II) and NADH. It is concluded that Tyr-dependent
DNA damage may play an important role in the carcinogenicity of TNM. TNM is a new
type of carcinogen that induces DNA damage not by itself but via Tyr
modification.
PMID- 17040109
TI - Analysis of crotonaldehyde- and acetaldehyde-derived 1,n(2)-propanodeoxyguanosine
adducts in DNA from human tissues using liquid chromatography electrospray
ionization tandem mass spectrometry.
AB - Crotonaldehyde, a mutagen and carcinogen, reacts with deoxyguanosine (dGuo) in
DNA to generate a pair of diastereomeric 1,N(2)()-propanodeoxyguanosine adducts
(Cro-dGuo, 2), which occur in (6S,8S) and (6R,8R) configurations. They can also
be formed through the consecutive reaction of two acetaldehyde molecules with
dGuo. Cro-dGuo adducts inhibit DNA synthesis and induce miscoding in human cells.
Considering their potential role in carcinogenesis, we have developed a sensitive
and specific liquid chromatography-electrospray ionization-tandem mass
spectrometry (LC-ESI-MS/MS) method to explore the presence of Cro-dGuo adducts in
DNA from various human tissues, such as liver, lung, and blood. DNA was isolated
from human tissues and enzymatically hydrolyzed to deoxyribonucleosides.
[(15)N(5)]Cro-dGuo was synthesized and used as an internal standard. The Cro-dGuo
adducts were enriched from the hydrolysate by solid-phase extraction and analyzed
by LC-ESI-MS/MS using selected reaction monitoring (SRM). This method allows the
quantitation of the Cro-dGuo adducts at a concentration of 4 fmol/micromol dGuo,
corresponding to about 1 adduct per 10(9) normal nucleosides starting with 1 mg
of DNA, with high accuracy and precision. DNA from human liver, lung, and blood
was analyzed. The Cro-dGuo adducts were detected more frequently in human lung
DNA than in liver DNA but were not detected in DNA from blood. The results of
this study provide quantified data on Cro-dGuo adducts in human tissues. The
higher frequency of Cro-dGuo in lung DNA than in the other tissues investigated
is potentially important and deserves further study.
PMID- 17040110
TI - Remission, a therapeutic goal in inflammatory arthropathies? Clinical data from
adalimumab studies.
AB - In recent years, there have been major advances in the management of rheumatoid
arthritis (RA), leading to the development of tumour necrosis factor (TNF)
antagonists. With these agents, it is possible to arrest joint damage and, by
treating early in the disease course, to prevent joint damage. It is also now
thought that early treatment can achieve clinical remission in a substantial
proportion of patients. With these increased expectations, a change is required
in the way clinical improvement and drug efficacy is measured. The existing
standard endpoint commonly used in RA clinical trials, the American College of
Rheumatology (ACR) 20% response measure, is inadequate for the new goals of
therapy that should be based on clinical remission and radiographic
assessment.Adalimumab, a fully human anti-TNF monoclonal antibody, has been shown
to be effective in achieving remission and preventing radiographic progression of
joint damage in patients with RA and other inflammatory arthropathies, including
psoriatic arthritis and ankylosing spondylitis. In a placebo-controlled trial in
patients with early RA, combination treatment with adalimumab plus methotrexate
(MTX) has been shown to be superior to either treatment alone in inducing
significant clinical remission while being generally well tolerated. Compared
with monotherapy, combination therapy resulted in significantly more patients
(49% vs 25%; p < 0.001) remaining in clinical remission after 2 years.
Suppression of joint damage assessed by the degree of inhibition of radiographic
progression was also significantly higher for patients treated with adalimumab
plus MTX (and with adalimumab alone) at 6 months, 1 and 2 years than for those
treated with MTX alone. These data support the notion that clinical remission is
a realistic therapeutic goal in patients with RA.
PMID- 17040111
TI - Antistaphylococcal vaccines and immunoglobulins: current status and future
prospects.
AB - Staphylococci are among the most frequently encountered pathogens in both the
inpatient and the outpatient setting. Management of infections caused by these
organisms is complicated by the increasingly common resistance of staphylococcal
pathogens to commonly used antibacterials. As a consequence, novel approaches to
prevention and treatment are urgently required. Such approaches include the
development of vaccines and immunoglobulin preparations targeted at virulence
factors expressed in vivo by staphylococci. This article reviews the
biopharmaceutical progress made to date in this field and suggests approaches to
further progress.
PMID- 17040112
TI - Short-term therapy for patients with hepatitis C virus genotype 2 or 3 infection.
AB - In the past 10 years, progress has been made in the management of patients with
chronic hepatitis C. A sustained virological response (SVR) is achieved in 80-85%
of patients infected with hepatitis C virus (HCV) genotype 2 or 3 after 24 weeks
of treatment with peginterferon-alpha and ribavirin. Treatment durations <24
weeks have been investigated to determine whether shorter-term therapy reduces
adverse effects and costs compared with longer-term therapy without compromising
efficacy. Three studies involving only patients with HCV genotype 2 or 3, with
different baseline patient characteristics have shown that 12-16 weeks of
treatment can be as effective as 24 weeks of treatment. In all three trials,
undetectable HCV RNA 4 weeks after the start of treatment was defined as rapid
virological response (RVR), and only patients with RVR stopped treatment early.
In the first trial, 75% of patients treated with peginterferon-alpha-2b and
ribavirin achieved RVR; these rapid responders achieved an SVR rate of 90% after
14 weeks of treatment. In the second trial, 63% of patients achieved RVR after 4
weeks of treatment with peginterferon-alpha-2b and ribavirin, and 85% of patients
with RVR achieved SVR after 12 weeks of treatment. In comparison, 91% of patients
with RVR treated for 24 weeks had SVR. In the third study, 93% of the total study
population achieved RVR and were randomly assigned to 16 or 24 weeks of treatment
with peginterferon-alpha-2a and ribavirin. Among patients with RVR, 85% in the
group treated for 16 weeks and 80% in the group treated for 24 weeks achieved
SVR. Among patients with HCV genotype 2 or 3, achieving an RVR to interferon
based treatment is common and a criterion to reduce the duration of treatment. In
patients with genotype 2 and RVR, 12 weeks of therapy with peginterferon-alpha
and ribavirin is recommended. For patients with genotype 3, a univocal
recommendation on treatment duration cannot be made. However, ongoing trials will
probably clarify this aspect.
PMID- 17040113
TI - Combination therapy in epilepsy: when and what to use.
AB - After being regarded as a last resort for over two decades, the role of
combination therapy as a treatment strategy for epilepsy is undergoing re
evaluation. This is a result of the growing appreciation that all seizures cannot
be controlled by monotherapy in a substantial proportion of patients, and of the
development of a range of modern antiepileptic drugs (AEDs), some of which are
better tolerated and less prone to complex pharmacokinetic drug interactions than
their older counterparts.Robust evidence to guide clinicians on when and how to
combine AEDs is lacking, and current practice recommendations are largely
empirical. Monotherapy should remain the treatment of choice for newly diagnosed
epilepsy. A combination of two AEDs can be considered after failure, resulting
from lack of efficacy, of one or two different monotherapy regimens. A few
patients will become seizure-free with a combination of three AEDs, but treatment
with a combination of four or more is unlikely to be successful. There is some
evidence to support a pharmacomechanistic approach to AED combination. Care
should be taken to avoid excessive drug load, which is associated with increased
toxicity. Bigger and better randomised, controlled studies are needed to
determine the optimal time and way to combine AEDs.
PMID- 17040115
TI - Corticosteroid-free strategies in liver transplantation.
AB - Corticosteroid avoidance is feasible and may be desirable in liver
transplantation. Approximately 50% of liver transplant recipients who use
calcineurin inhibitors and azathioprine do not need corticosteroids. The
availability of newer agents, such as mycophenolate mofetil and antibody therapy,
has increased the percentage of patients who do not need to use corticosteroids
to about 75%. The feasibility of corticosteroid-free immunosuppression has been
established by controlled trials demonstrating non-inferiority with respect to
patterns of rejection as well as patient and graft survival. However, the
evidence available to date does not unequivocally establish the benefits of
corticosteroid-free immunosuppression, although some advantage has been
established relating to post-transplant diabetes mellitus, cytomegalovirus
infection and growth patterns in children. The effect of corticosteroid-free
immunosuppression in hepatitis C liver transplant recipients is yet to be
resolved.
PMID- 17040114
TI - Natural course, therapeutic options and economic evaluation of therapies for
chronic hepatitis B.
AB - Chronic hepatitis B virus infection afflicts 400 million people worldwide and
untreated will progress to cirrhosis in 15-40% of individuals, with an associated
increased risk for the development of hepatocellular carcinoma. The 'inactive
carrier state' carries a benign prognosis with a very low risk of cirrhosis or
hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive
chronic hepatitis state is an active disease state with increased risk for
progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant
variety of chronic hepatitis B has been associated with a higher incidence of
cirrhosis at initial presentation and more frequent progression to hepatocellular
carcinoma compared with the wild-type hepatitis B. Five medications are currently
approved by the US FDA for the treatment of chronic hepatitis B: interferon
alpha, lamivudine, adefovir dipivoxil, entecavir and peginterferon-alpha-2a.
Interferon-alpha therapy has been shown to increase the rate of HBeAg and
hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but
has significant adverse effects and is ineffective against the HBeAg-negative
mutant. Lamivudine is a safely used, orally administered drug with good efficacy,
but is associated with the development of a lamivudine-resistant (Lam-R) mutant
in a large proportion of patients after long-term therapy. High relapse rates
after lamivudine therapy make this medication less effective in the HBeAg
negative mutant also. Adefovir dipivoxil is a safely used, orally administered
drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is
effective against the wild-type and HBeAg-negative hepatitis B and has a very low
incidence of resistance development. Entecavir is a highly potent and selective
new oral drug against hepatitis B. It has demonstrated no resistance development
in treatment-naive patients, but a low incidence of resistance in patients
infected with prior Lam-R mutants. Peginterferon-alpha-2a is administered once
weekly and has improved efficacy compared with standard interferon-alpha and
lamivudine. However, it has a similar adverse-effect profile to standard
interferon-alpha. Pharmacoeconomic studies have demonstrated a cost benefit in
treating chronic hepatitis B patients compared with no therapy. However, results
have been conflicting, with earlier studies showing a cost advantage of
lamivudine over interferon-alpha and a more recent, comprehensive study favouring
interferon-alpha monotherapy in HBeAg-negative patients and adefovir dipivoxil
'salvage' after lamivudine resistance development in HBeAg-positive patients.
PMID- 17040116
TI - Pioglitazone/metformin.
AB - A fixed-dose pioglitazone/metformin tablet is approved in the US and the EU for
the treatment of adult patients with type 2 diabetes mellitus who currently have
inadequate glycaemic control with metformin monotherapy. In the US, the
combination tablet is also approved for the treatment of adult patients with type
2 diabetes who currently have inadequate glycaemic control with pioglitazone
monotherapy and for those already receiving a combination of pioglitazone and
metformin. Bioequivalence, based on absorption and bioavailability parameters,
has been established between the fixed-dose tablets and equivalent doses of
pioglitazone and metformin coadministered as separate agents. Combination therapy
with pioglitazone plus metformin was significantly more effective at improving
both glycaemic and lipid control than metformin plus placebo in patients with
type 2 diabetes in a 16-week, well designed trial. Pioglitazone plus metformin
demonstrated similar antihyperglycaemic efficacy to that of rosiglitazone plus
metformin in a well designed 12-month trial; however, pioglitazone plus metformin
was the superior combination in terms of lipid control. In several comparative
trials of 1-3.5 years' duration, pioglitazone plus metformin was at least as
effective as combination therapy with a sulphonylurea plus metformin in terms of
antihyperglycaemic efficacy, but provided superior lipidaemic control with regard
to levels of triglyceride and high-density lipoprotein-cholesterol. Pioglitazone
plus metformin was generally well tolerated in patients with type 2 diabetes,
with adverse events common to metformin monotherapy observed at a similar
incidence to that with metformin plus placebo.
PMID- 17040120
TI - Valsartan/hydrochlorothiazide: a review of its use in the management of
hypertension.
AB - Valsartan/hydrochlorothiazide is a fixed-dose (valsartan 80, 160 or 320mg plus
hydrochlorothiazide 12.5 or 25mg) angiotensin II receptor blocker/diuretic drug
combination indicated for the treatment of patients with essential hypertension
not adequately controlled by monotherapy.There is ample evidence that
valsartan/hydrochlorothiazide is an effective fixed-dose combination
antihypertensive agent. However, efficacy and tolerability data pertaining to the
320mg dose of valsartan in the combination are currently relatively few. There is
also some evidence of potential benefits associated with the relatively
favourable tolerability profile of the combination, the low occurrence of new
onset diabetes mellitus versus amlodipine and the valsartan-associated
improvements in cardiac and endothelial function.
PMID- 17040121
TI - Large-scale turnover of functional transcription factor binding sites in
Drosophila.
AB - The gain and loss of functional transcription factor binding sites has been
proposed as a major source of evolutionary change in cis-regulatory DNA and gene
expression. We have developed an evolutionary model to study binding-site
turnover that uses multiple sequence alignments to assess the evolutionary
constraint on individual binding sites, and to map gain and loss events along a
phylogenetic tree. We apply this model to study the evolutionary dynamics of
binding sites of the Drosophila melanogaster transcription factor Zeste, using
genome-wide in vivo (ChIP-chip) binding data to identify functional Zeste binding
sites, and the genome sequences of D. melanogaster, D. simulans, D. erecta, and
D. yakuba to study their evolution. We estimate that more than 5% of functional
Zeste binding sites in D. melanogaster were gained along the D. melanogaster
lineage or lost along one of the other lineages. We find that Zeste-bound regions
have a reduced rate of binding-site loss and an increased rate of binding-site
gain relative to flanking sequences. Finally, we show that binding-site gains and
losses are asymmetrically distributed with respect to D. melanogaster, consistent
with lineage-specific acquisition and loss of Zeste-responsive regulatory
elements.
PMID- 17040122
TI - Viral and latent reservoir persistence in HIV-1-infected patients on therapy.
AB - Despite many years of potent antiretroviral therapy, latently infected cells and
low levels of plasma virus have been found to persist in HIV-infected patients.
The factors influencing this persistence and their relative contributions have
not been fully elucidated and remain controversial. Here, we address these issues
by developing and employing a simple, but mechanistic viral dynamics model. The
model has two novel features. First, it assumes that latently infected T cells
can undergo bystander proliferation without transitioning into active viral
production. Second, it assumes that the rate of latent cell activation decreases
with time on antiretroviral therapy due to the activation and subsequent loss of
latently infected cells specific for common antigens, leaving behind cells that
are successively less frequently activated. Using the model, we examined the
quantitative contributions of T cell bystander proliferation, latent cell
activation, and ongoing viral replication to the stability of the latent
reservoir and persisting low-level viremia. Not surprisingly, proliferation of
latently infected cells helped maintain the latent reservoir in spite of loss of
latent infected cells through activation and death, and affected viral dynamics
to an extent that depended on the magnitude of latent cell activation. In the
limit of zero latent cell activation, the latent cell pool and viral load became
uncoupled. However, as the activation rate increased, the plasma viral load could
be maintained without depleting the latent reservoir, even in the absence of
viral replication. The influence of ongoing viral replication on the latent
reservoir remained insignificant for drug efficacies above the "critical
efficacy" irrespective of the activation rate. However, for lower drug efficacies
viral replication enabled the stable maintenance of both the latent reservoir and
the virus. Our model and analysis methods provide a quantitative and qualitative
framework for probing how different viral and host factors contribute to the
dynamics of the latent reservoir and the virus, offering new insights into the
principal determinants of their persistence.
PMID- 17040123
TI - Quantitative analyses of circadian gene expression in mammalian cell cultures.
AB - The central circadian pacemaker is located in the hypothalamus of mammals, but
essentially the same oscillating system operates in peripheral tissues and even
in immortalized cell lines. Using luciferase reporters that allow automated
monitoring of circadian gene expression in mammalian fibroblasts, we report the
collection and analysis of precise rhythmic data from these cells. We use these
methods to analyze signaling pathways of peripheral tissues by studying the
responses of Rat-1 fibroblasts to ten different compounds. To quantify these
rhythms, which show significant variation and large non-stationarities (damping
and baseline drifting), we developed a new fast Fourier transform-nonlinear least
squares analysis procedure that specifically optimizes the quantification of
amplitude for circadian rhythm data. This enhanced analysis method successfully
distinguishes among the ten signaling compounds for their rhythm-inducing
properties. We pursued detailed analyses of the responses to two of these
compounds that induced the highest amplitude rhythms in fibroblasts, forskolin
(an activator of adenylyl cyclase), and dexamethasone (an agonist of
glucocorticoid receptors). Our quantitative analyses clearly indicate that the
synchronization mechanisms by the cAMP and glucocorticoid pathways are different,
implying that actions of different genes stimulated by these pathways lead to
distinctive programs of circadian synchronization.
PMID- 17040124
TI - The role of compensatory mutations in the emergence of drug resistance.
AB - Pathogens that evolve resistance to drugs usually have reduced fitness. However,
mutations that largely compensate for this reduction in fitness often arise. We
investigate how these compensatory mutations affect population-wide resistance
emergence as a function of drug treatment. Using a model of gonorrhea
transmission dynamics, we obtain generally applicable, qualitative results that
show how compensatory mutations lead to more likely and faster resistance
emergence. We further show that resistance emergence depends on the level of drug
use in a strongly nonlinear fashion. We also discuss what data need to be
obtained to allow future quantitative predictions of resistance emergence.
PMID- 17040125
TI - Phylogenetic relationships of the Wolbachia of nematodes and arthropods.
AB - Wolbachia are well known as bacterial symbionts of arthropods, where they are
reproductive parasites, but have also been described from nematode hosts, where
the symbiotic interaction has features of mutualism. The majority of arthropod
Wolbachia belong to clades A and B, while nematode Wolbachia mostly belong to
clades C and D, but these relationships have been based on analysis of a small
number of genes. To investigate the evolution and relationships of Wolbachia
symbionts we have sequenced over 70 kb of the genome of wOvo, a Wolbachia from
the human-parasitic nematode Onchocerca volvulus, and compared the genes
identified to orthologues in other sequenced Wolbachia genomes. In comparisons of
conserved local synteny, we find that wBm, from the nematode Brugia malayi, and
wMel, from Drosophila melanogaster, are more similar to each other than either is
to wOvo. Phylogenetic analysis of the protein-coding and ribosomal RNA genes on
the sequenced fragments supports reciprocal monophyly of nematode and arthropod
Wolbachia. The nematode Wolbachia did not arise from within the A clade of
arthropod Wolbachia, and the root of the Wolbachia clade lies between the
nematode and arthropod symbionts. Using the wOvo sequence, we identified a
lateral transfer event whereby segments of the Wolbachia genome were inserted
into the Onchocerca nuclear genome. This event predated the separation of the
human parasite O. volvulus from its cattle-parasitic sister species, O. ochengi.
The long association between filarial nematodes and Wolbachia symbionts may
permit more frequent genetic exchange between their genomes.
PMID- 17040126
TI - COPI activity coupled with fatty acid biosynthesis is required for viral
replication.
AB - During infection by diverse viral families, RNA replication occurs on the surface
of virally induced cytoplasmic membranes of cellular origin. How this process is
regulated, and which cellular factors are required, has been unclear. Moreover,
the host-pathogen interactions that facilitate the formation of this new
compartment might represent critical determinants of viral pathogenesis, and
their elucidation may lead to novel insights into the coordination of vesicular
trafficking events during infection. Here we show that in Drosophila cells,
Drosophila C virus remodels the Golgi apparatus and forms a novel vesicular
compartment, on the surface of which viral RNA replication takes place. Using
genome-wide RNA interference screening, we found that this step in the viral
lifecycle requires at least two host encoded pathways: the coat protein complex I
(COPI) coatamer and fatty acid biosynthesis. Our results integrate, clarify, and
extend numerous observations concerning the cell biology of viral replication,
allowing us to conclude that the coupling of new cellular membrane formation with
the budding of these vesicles from the Golgi apparatus allows for the regulated
generation of this new virogenic organelle, which is essential for viral
replication. Additionally, because these pathways are also limiting in flies and
in human cells infected with the related RNA virus poliovirus, they may represent
novel targets for antiviral therapies.
PMID- 17040127
TI - Terminal reassortment drives the quantum evolution of type III effectors in
bacterial pathogens.
AB - Many bacterial pathogens employ a type III secretion system to deliver type III
secreted effectors (T3SEs) into host cells, where they interact directly with
host substrates to modulate defense pathways and promote disease. This
interaction creates intense selective pressures on these secreted effectors,
necessitating rapid evolution to overcome host surveillance systems and defenses.
Using computational and evolutionary approaches, we have identified numerous
mosaic and truncated T3SEs among animal and plant pathogens. We propose that
these secreted virulence genes have evolved through a shuffling process we have
called "terminal reassortment." In terminal reassortment, existing T3SE termini
are mobilized within the genome, creating random genetic fusions that result in
chimeric genes. Up to 32% of T3SE families in species with relatively large and
well-characterized T3SE repertoires show evidence of terminal reassortment, as
compared to only 7% of non-T3SE families. Terminal reassortment may permit the
near instantaneous evolution of new T3SEs and appears responsible for major
modifications to effector activity and function. Because this process plays a
more significant role in the evolution of T3SEs than non-effectors, it provides
insight into the evolutionary origins of T3SEs and may also help explain the
rapid emergence of new infectious agents.
PMID- 17040128
TI - Two Plasmodium rhomboid proteases preferentially cleave different adhesins
implicated in all invasive stages of malaria.
AB - Invasion of host cells by the malaria pathogen Plasmodium relies on parasite
transmembrane adhesins that engage host-cell receptors. Adhesins must be released
by cleavage before the parasite can enter the cell, but the processing enzymes
have remained elusive. Recent work indicates that the Toxoplasma rhomboid
intramembrane protease TgROM5 catalyzes this essential cleavage. However,
Plasmodium does not encode a direct TgROM5 homolog. We examined processing of the
14 Plasmodium falciparum adhesins currently thought to be involved in invasion by
both model and Plasmodium rhomboid proteases in a heterologous assay. While most
adhesins contain aromatic transmembrane residues and could not be cleaved by
nonparasite rhomboid proteins, including Drosophila Rhomboid-1, Plasmodium
falciparum rhomboid protein (PfROM)4 (PFE0340c) was able to process these
adhesins efficiently and displayed novel substrate specificity. Conversely,
PfROM1 (PF11_0150) shared specificity with rhomboid proteases from other
organisms and was the only PfROM able to cleave apical membrane antigen 1 (AMA1).
PfROM 1 and/or 4 was thus able to cleave diverse adhesins including TRAP, CTRP,
MTRAP, PFF0800c, EBA-175, BAEBL, JESEBL, MAEBL, AMA1, Rh1, Rh2a, Rh2b, and Rh4,
but not PTRAMP, and cleavage relied on the adhesin transmembrane domains.
Swapping transmembrane regions between BAEBL and AMA1 switched the relative
preferences of PfROMs 1 and 4 for these two substrates. Our analysis indicates
that PfROMs 1 and 4 function with different substrate specificities that together
constitute the specificity of TgROM5 to cleave diverse adhesins. This is the
first enzymatic analysis of Plasmodium rhomboid proteases and suggests an
involvement of PfROMs in all invasive stages of the malaria lifecycle, in both
the vertebrate host and the mosquito vector.
PMID- 17040130
TI - Cell size checkpoint control by the retinoblastoma tumor suppressor pathway.
AB - Size control is essential for all proliferating cells, and is thought to be
regulated by checkpoints that couple cell size to cell cycle progression. The
aberrant cell-size phenotypes caused by mutations in the retinoblastoma (RB)
tumor suppressor pathway are consistent with a role in size checkpoint control,
but indirect effects on size caused by altered cell cycle kinetics are difficult
to rule out. The multiple fission cell cycle of the unicellular alga
Chlamydomonas reinhardtii uncouples growth from division, allowing direct
assessment of the relationship between size phenotypes and checkpoint function.
Mutations in the C. reinhardtii RB homolog encoded by MAT3 cause supernumerous
cell divisions and small cells, suggesting a role for MAT3 in size control. We
identified suppressors of an mat3 null allele that had recessive mutations in DP1
or dominant mutations in E2F1, loci encoding homologs of a heterodimeric
transcription factor that is targeted by RB-related proteins. Significantly, we
determined that the dp1 and e2f1 phenotypes were caused by defects in size
checkpoint control and were not due to a lengthened cell cycle. Despite their
cell division defects, mat3, dp1, and e2f1 mutants showed almost no changes in
periodic transcription of genes induced during S phase and mitosis, many of which
are conserved targets of the RB pathway. Conversely, we found that regulation of
cell size was unaffected when S phase and mitotic transcription were inhibited.
Our data provide direct evidence that the RB pathway mediates cell size
checkpoint control and suggest that such control is not directly coupled to the
magnitude of periodic cell cycle transcription.
PMID- 17040132
TI - Functionality of intergenic transcription: an evolutionary comparison.
AB - Although a large proportion of human transcription occurs outside the boundaries
of known genes, the functional significance of this transcription remains
unknown. We have compared the expression patterns of known genes as well as
intergenic transcripts within the ENCODE regions between humans and chimpanzees
in brain, heart, testis, and lymphoblastoid cell lines. We find that intergenic
transcripts show patterns of tissue-specific conservation of their expression,
which are comparable to exonic transcripts of known genes. This suggests that
intergenic transcripts are subject to functional constraints that restrict their
rate of evolutionary change as well as putative positive selection to an extent
comparable to that of classical protein-coding genes. In brain and testis, we
find that part of this intergenic transcription is caused by widespread use of
alternative promoters. Further, we find that about half of the expression
differences between humans and chimpanzees are due to intergenic transcripts.
PMID- 17040135
TI - AAHPM College of Palliative Care: mentorship and career development.
PMID- 17040131
TI - Forces shaping the fastest evolving regions in the human genome.
AB - Comparative genomics allow us to search the human genome for segments that were
extensively changed in the last approximately 5 million years since divergence
from our common ancestor with chimpanzee, but are highly conserved in other
species and thus are likely to be functional. We found 202 genomic elements that
are highly conserved in vertebrates but show evidence of significantly
accelerated substitution rates in human. These are mostly in non-coding DNA,
often near genes associated with transcription and DNA binding. Resequencing
confirmed that the five most accelerated elements are dramatically changed in
human but not in other primates, with seven times more substitutions in human
than in chimp. The accelerated elements, and in particular the top five, show a
strong bias for adenine and thymine to guanine and cytosine nucleotide changes
and are disproportionately located in high recombination and high guanine and
cytosine content environments near telomeres, suggesting either biased gene
conversion or isochore selection. In addition, there is some evidence of
directional selection in the regions containing the two most accelerated regions.
A combination of evolutionary forces has contributed to accelerated evolution of
the fastest evolving elements in the human genome.
PMID- 17040129
TI - Inferring the demographic history and rate of adaptive substitution in
Drosophila.
AB - An important goal of population genetics is to determine the forces that have
shaped the pattern of genetic variation in natural populations. We developed a
maximum likelihood method that allows us to infer demographic changes and detect
recent positive selection (selective sweeps) in populations of varying size from
DNA polymorphism data. Applying this approach to single nucleotide polymorphism
data at more than 250 noncoding loci on the X chromosome of Drosophila
melanogaster from an (ancestral) African population and a (derived) European, we
found that the African population expanded about 60,000 y ago and that the
European population split off from the African lineage about 15,800 y ago,
thereby suffering a severe population size bottleneck. We estimated that about
160 beneficial mutations (with selection coefficients s between 0.05% and 0.5%)
were fixed in the euchromatic portion of the X in the African population since
population size expansion, and about 60 mutations (with s around 0.5%) in the
diverging European lineage.
PMID- 17040136
TI - Iraq of the palliative care movement.
PMID- 17040139
TI - Preventing burnout.
PMID- 17040140
TI - Applying the concepts from Maslow in a large U.S. hospice program.
PMID- 17040141
TI - A central role for palliative care in an influenza pandemic.
PMID- 17040142
TI - Palliative care services in Pennsylvania nursing homes.
AB - BACKGROUND: Palliative care is an interdisciplinary model that focuses on the
comprehensive management of physical, psychological, social, and spiritual needs
of individuals with lifelimiting illness. Although palliative care is
increasingly common in acute care settings, regulatory, financial, and
educational barriers often bar nursing home residents from access to palliative
care services. OBJECTIVE: The purpose of the Palliative Care Services in
Pennsylvania Nursing Homes Survey was to describe existing palliative care
services within nursing homes in Pennsylvania, and to classify these services by
level of care delivery. METHODS: Ninety-one nursing home administrators
throughout the state of Pennsylvania participated in the mailed survey. Multiple
logistic regression analysis was used to investigate the association between
various organizational characteristics and provision of palliative care services.
RESULTS: Results reveal that urban facilities were more likely to provide
palliative care services than rural facilities. Urban facilities cited the need
for bereavement training most frequently, whereas rural clinical cited the need
for training in pain management. Larger facility size was associated with an
increased likelihood of pain management practices, even after adjusting for
regional differences. CONCLUSIONS: These pilot findings are consistent with and
extend previous findings suggesting that palliative care practice in nursing
homes is strongly influenced by nonclinical factors and invites further
investigation.
PMID- 17040143
TI - Errors in symptom intensity self-assessment by patients receiving outpatient
palliative care.
AB - BACKGROUND: Patient-based symptom scores are the standard method for assessment
in palliative care. There has been limited research on the frequency of errors
upon using this approach. The Edmonton Symptom Assessment Scale (ESAS) is a
reliable and valid assessment tool routinely used for symptom intensity
assessment in our cancer center. OBJECTIVE: To determine if patients were scoring
the symptoms on the ESAS in the way it was supposed to be scored. SETTINGS: The
study was carried out at the outpatient palliative care center. DESIGN AND
SUBJECTS: Retrospective review of 60 consecutive patient charts was done where
the patient had initially scored the ESAS. The physician looked at this scoring
on the ESAS and went back to the patient to do the scoring again to see if the
patient had scored it in the way it was intended to be scored. The same physician
did the assessment on all of the patients. OUTCOME MEASURES: Level of agreement
(weighted kappa) before versus after the physician visit; Screening performance
of patient completed ESAS for mild and moderate symptom intensity. RESULTS:
Complete agreement ranged from 58% (sleep) to 82% (well-being); the weighted
kappa ranged from 0.49 (drowsiness) to 0.78 (well-being). There was more
agreement for symptoms such as dyspnea, nausea, anxiety, and depression and less
agreement for symptoms such as lack of sleep and lack of appetite. The screening
performance of the initial patient self assessment showed less sensitivity for
nausea, drowsiness if the intensity was mild and less sensitivity for pain,
nausea, anxiety, and drowsiness if the intensity was moderate. CONCLUSIONS:
Vigilance needs to be maintained about the ESAS scores done by the patients
particularly for symptoms of sleep, appetite, and pain. There is a likelihood of
error if doctors or nurses do not routinely check the way patients have completed
the assessment form. More research is needed to determine the best way to teach
patients how to minimize errors in self-reporting of symptoms.
PMID- 17040145
TI - Racial differences in next-of-kin participation in an ongoing survey of
satisfaction with end-of-life care: a study of a study.
AB - Despite disparities in health care access and quality, African Americans are
underrepresented in many areas of clinical investigation, including research in
end-of-life care. Because of the importance of surrogate reports in assessing the
quality of end-of-life care, this study examined racial differences in next-of
kin participation in an ongoing study of satisfaction with end-of-life care. The
parent study includes after-death interviews with next-of-kin of elderly African
Americans and Caucasians who died at Duke Hospital. This analysis included next
of-kin of elders who died at Duke Hospital from December 1, 2003 to December 31,
2004. During this period, there were 471 decedents whose next-of-kin were
eligible for participation. Of these, 133 (28%) were African American and 338
(72%) were Caucasian. There were no racial differences in completion, contact, or
overall response rates. Of those contacted, 39.8% of African Americans and 37.8%
of Caucasians completed the study. In multivariate analysis, only the
relationship of the next-of-kin to the decedent was an independent predictor of
study completion. Children of decedents were significantly more likely to
participate than spouses (odds ratio [OR] 2.1 [1.14, 3.86]). In this analysis,
next-of-kin of African American and Caucasian decedents were equally likely to
participate in an after-death interview assessing satisfaction with end-of-life
care. The use of racially concordant interviewers, subject identification with
the institution, and the absence of socioeconomic constraints may partly explain
these findings. Given the growing diversity of the U.S. population, researchers
in end-of-life care must use strategies aimed at recruiting racially and
ethnically diverse samples.
PMID- 17040144
TI - Use of Palliative Performance Scale in end-of-life prognostication.
AB - BACKGROUND: Current literature suggests clinicians are not accurate in
prognostication when estimating survival times of palliative care patients. There
are reported studies in which the Palliative Performance Scale (PPS) is used as a
prognostic tool to predict survival of these patients. Yet, their findings are
different in terms of the presence of distinct PPS survival profiles and
significant covariates. OBJECTIVE: This study investigates the use of PPS as a
prognostication tool for estimating survival times of patients with life-limiting
illness in a palliative care unit. These findings are compared to those from
earlier studies in terms of PPS survival profiles and covariates. METHODS: This
is a retrospective cohort study in which the admission PPS scores of 733
palliative care patients admitted between March 3, 2000 and August 9, 2002 were
examined for survival patterns. Other predictors for survival included were age,
gender, and diagnosis. RESULTS: Study findings revealed that admission PPS score
was a strong predictor of survival in patients already identified as palliative,
along with gender and age, but diagnosis was not significantly related to
survival. We also found that scores of PPS 10% through PPS 50% led to distinct
survival curves, and male patients had consistently lower survival rates than
females regardless of PPS score. CONCLUSION: Our findings differ somewhat from
earlier studies that suggested the presence of three distinct PPS survival
profiles or bands, with diagnosis and noncancer as significant covariates. Such
differences are likely attributed to the size and characteristics of the patient
populations involved and further analysis with larger patient samples may help
clarify PPS use in prognosis.
PMID- 17040146
TI - Psychometric characteristics of a quality of communication questionnaire
assessing communication about end-of-life care.
AB - The importance of good clinician-patient communication to quality end-of-life
care has been well documented yet there are no validated measures that allow
patients to assess the quality of this communication. Using a sample of hospice
patients (n = 83) and patients with chronic obstructive pulmonary disease (COPD)
(n = 113), we evaluated the psychometric characteristics of a 13-item patient
centered, patient-report questionnaire about the quality of end-of-life
communication (QOC). Our purpose was to explore the measurement structure of the
QOC items to ascertain if the items represent unitary or multidimensional
constructs and to describe the construct validity of the QOC score(s). Analyses
included: principal component analyses to identify scales, internal consistency
analyses to demonstrate reliability, and correlational and group comparisons to
support construct validity. Findings support the construction of two scales: a
six-item "general communication skills" scale and a seven-item, "communication
about end-of-life care" scale. The two scales meet standards of scale
measurement, including good factor convergence (values >or= 0.63) and
discrimination (values different >or= 0.25), percent of variance explained
(69.3%), and good internal consistency (alpha >or= 0.79). The scales' construct
validity is supported by significant associations (p Asp amino acid substitution)
and A252G polymorphisms of the LTA gene and the C3279T polymorphism of the
galectin-2 (LGALS2) gene, which affects LTA secretion, are associated with
inflammatory parameters and cell adhesion molecules, and whether these
polymorphisms are related to CHD in American women and men. We conducted a
prospective nested case-control study within the Nurses' Health Study and Health
Professionals Follow-Up Study. Among participants free of cardiovascular disease
at baseline, 249 women and 266 men developed CHD during 8 and 6 years of follow
up respectively, and we matched controls 2:1 based on age and smoking. The LGALS2
gene variant was significantly associated with a decreased risk of CHD in women
[odds ratio (95% confidence interval), 0.70 (0.50-0.97); P=0.03]. In addition,
the LGALS2 polymorphism was directly associated with CRP (C-reactive protein)
levels in cases from both studies (P<0.05). The LTA gene polymorphisms were
directly associated with levels of sTNFRs (soluble tumour necrosis factor
receptors) and VCAM-1 (vascular cell adhesion molecule-1) in both women and men
with CHD (P<0.05). However, no overall effect was demonstrated between LTA gene
polymorphisms and risk of CHD.
PMID- 17040206
TI - Depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence
in African trypanosomes.
AB - In trypanosomes, the thioredoxin-type protein TXN (tryparedoxin) is a multi
purpose oxidoreductase that is involved in the detoxification of hydroperoxides,
the synthesis of DNA precursors and the replication of the kinetoplastid DNA.
African trypanosomes possess two isoforms that are localized in the cytosol and
in the mitochondrion of the parasites respectively. Here we report on the
biological significance of the cTXN (cytosolic TXN) of Trypanosoma brucei for
hydroperoxide detoxification. Depending on the growth phase, the concentration of
the protein is 3-7-fold higher in the parasite form infecting mammals (50-100
microM) than in the form hosted by the tsetse fly (7-34 microM). Depletion of the
mRNA in bloodstream trypanosomes by RNA interference revealed the
indispensability of the protein. Proliferation and viability of cultured
trypanosomes were impaired when TXN was lowered to 1 muM for more than 48 h.
Although the levels of glutathione, glutathionylspermidine and trypanothione were
increased 2-3.5-fold, the sensitivity against exogenously generated H2O2 was
significantly enhanced. The results prove the essential role of the cTXN and its
pivotal function in the parasite defence against oxidative stress.
PMID- 17040207
TI - Seven Dictyostelium discoideum phosphodiesterases degrade three pools of cAMP and
cGMP.
AB - The Dictyostelium discoideum genome uncovers seven cyclic nucleotide PDEs
(phosphodiesterases), of which six have been characterized previously and the
seventh is characterized in the present paper. Three enzymes belong to the
ubiquitous class I PDEs, common in all eukaryotes, whereas four enzymes belong to
the rare class II PDEs that are present in bacteria and lower eukaryotes. Since
all D. discoideum PDEs are now characterized we have calculated the contribution
of each enzyme in the degradation of the three important pools of cyclic
nucleotides: (i) extracellular cAMP that induces chemotaxis during aggregation
and differentiation in slugs; (ii) intracellular cAMP that mediates development;
and (iii) intracellular cGMP that mediates chemotaxis. It appears that each
cyclic nucleotide pool is degraded by a combination of enzymes that have
different affinities, allowing a broad range of substrate concentrations to be
degraded with first-order kinetics. Extracellular cAMP is degraded predominantly
by the class II high-affinity enzyme DdPDE1 and its close homologue DdPDE7, and
in the multicellular stage also by the low-affinity transmembrane class I enzyme
DdPDE4. Intracellular cAMP is degraded by the DdPDE2, a class I enzyme regulated
by histidine kinase/phospho-relay, and by the cAMP-/cGMP-stimulated class II
DdPDE6. Finally, basal intracellular cGMP is degraded predominantly by the high
affinity class I DdPDE3, while the elevated cGMP levels that arise after receptor
stimulation are degraded predominantly by a cGMP-stimulated cGMP-specific class
II DdPDE5. The analysis shows that the combination of enzymes is tuned to keep
the concentration and lifetime of the substrate within a functional range.
PMID- 17040208
TI - Role of Ca2+ activation and bilobal structure of calmodulin in nuclear and
nucleolar localization.
AB - Ca2+ signalling to the nucleus is thought to occur by calmodulin entry into the
nucleus where calmodulin has many functions. In the present study we have
investigated the role of Ca2+ and the N- and C-terminal lobes of calmodulin in
its subnuclear targeting by using fluorescently labelled calmodulin and its
mutants and confocal microscopy. Our data show, first, that Ca2+ stimulation
induces a reorganization of subnuclear structures to which apo-calmodulin can
bind. Secondly, Ca2+-independent association of the C-terminal lobe is seen with
subnuclear structures such as chromatin, the nuclear envelope and the nucleoli.
Thirdly, Ca2+-dependent accumulation of both calmodulin and the C-terminal
calmodulin lobe occurs in the nucleoli. The N-terminal lobe of calmodulin does
not show significant binding to subnuclear structures although, similarly to the
C-terminal lobe, it accumulates in the nucleoplasm of wheat germ agglutinin
blocked nuclei suggesting that a facilitated nuclear export mechanism exists for
calmodulin.
PMID- 17040209
TI - Identification of a novel targeting sequence for regulated secretion in the
serine protease inhibitor neuroserpin.
AB - Ns (neuroserpin) is a member of the serpin (serine protease inhibitor) gene
family that is primarily expressed within the central nervous system. Its
principal target protease is tPA (tissue plasminogen activator), which is thought
to contribute to synaptic plasticity and to be secreted in a stimulus-dependent
manner. In the present study, we demonstrate in primary neuronal cultures that Ns
co-localizes in LDCVs (large dense core vesicles) with the regulated secretory
protein chromogranin B. We also show that Ns secretion is regulated and can be
specifically induced 4-fold by secretagogue treatment. A novel 13-amino-acid
sorting signal located at the C-terminus of Ns is identified that is both
necessary and sufficient to target Ns to the regulated secretion pathway. Its
deletion renders Ns no longer responsive to secretagogue stimulation, whereas PAI
Ns [Ns (neuroserpin)-PAI-1 (plasminogen activator inhibitor-1) chimaera appending
the last 13 residues of Ns sequence to the C-terminus of PAI-1] shifts PAI-1
secretion into a regulated secretory pathway.
PMID- 17040211
TI - Comparison of early and late toxic effects of sulfur mustard in Iranian veterans.
AB - Sulfur mustard is an alkylating agent that reacts with ocular, respiratory,
cutaneous, and bone marrow tissues, resulting in early and late toxic effects. We
compare these effects based on the experience in Iranian veterans exposed to the
agent during the Iran-Iraq conflict (1983-88). The first clinical manifestations
of sulfur mustard poisoning occurred in the eyes with a sensation of grittiness,
lacrimation, photophobia, blepharospasm, and corneal ulceration. Respiratory
effects appeared as rhinorhea, laryngitis, tracheobronchitis, and dyspnoea. Skin
lesions varied from erythema to bullous necrotization. Initial leukocytosis and
lymphopenia returned to normal within four weeks in recovered patients, but
marked cytopenia with bone marrow failure occurred in fatal cases. Late toxic
effects of sulfur mustard were most commonly found in lungs, skin and eyes. Main
respiratory complications were chronic obstructive pulmonary disease,
bronchiectasis, asthma, large airway narrowing, and pulmonary fibrosis. Late skin
lesions were hyperpigmentation, dry skin, atrophy, and hypopigmentation. Fifteen
of the severely intoxicated patients were diagnosed with delayed keratitis,
having corneal vascularization, thinning, and epithelial defect. Respiratory
complications exacerbated over time, while cutaneous and ocular lesions decreased
or remained constant. Both the severity and frequency of bronchiectatic lesions
increased during long-term follow-up. The only deteriorating cutaneous
complication was dry skin. The maximum incidence of delayed kaeratitis was
observed 15 to 20 years after initial exposure. Being suggested as the main cause
ofassociated with malignancies and recurrent infections, natural killer cells
were significantly lower 16 to 20 years after intoxication.
PMID- 17040210
TI - BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in
vitro and in vivo.
AB - Hormones and growth factors induce the activation of a number of protein kinases
that belong to the AGC subfamily, including isoforms of PKA, protein kinase B
(also known as Akt), PKC, S6K p70 (ribosomal S6 kinase), RSK (p90 ribosomal S6
kinase) and MSK (mitogen- and stress-activated protein kinase), which then
mediate many of the physiological processes that are regulated by these
extracellular agonists. It can be difficult to assess the individual functions of
each AGC kinase because their substrate specificities are similar. Here we
describe the small molecule BI-D1870, which inhibits RSK1, RSK2, RSK3 and RSK4 in
vitro with an IC(50) of 10-30 nM, but does not signi-ficantly inhibit ten other
AGC kinase members and over 40 other protein kinases tested at 100-fold higher
concentrations. BI-D1870 is cell permeant and prevents the RSK-mediated phorbol
ester- and EGF (epidermal growth factor)-induced phosphoryl-ation of glycogen
synthase kinase-3beta and LKB1 in human embry-onic kidney 293 cells and Rat-2
cells. In contrast, BI-D1870 does not affect the agonist-triggered
phosphorylation of substrates for six other AGC kinases. Moreover, BI-D1870 does
not suppress the phorbol ester- or EGF-induced phosphorylation of CREB (cAMP
response-element-binding protein), consistent with the genetic evidence
indicating that MSK, and not RSK, isoforms mediate the mitogen-induced
phosphorylation of this transcription factor.
PMID- 17040212
TI - The established and emerging uses of aspirin.
AB - In this paper, summary narratives on the established and emerging uses of aspirin
are presented. On the former, aspirin is used to treat conditions such as
headache and also reduce the risks associated with cardiovascular disease and
also with pre-eclampsia. On the latter, aspirin might be taken more widely by
individuals over 50 years, used as a dietary supplement to possibly reduce cancer
risk and used post-transplant to improve organ survival. Aspirin will continue to
be an important therapeutic agent and to generate considerable interest among the
research community for the foreseeable future.
PMID- 17040213
TI - New melanocortin 1 receptor binding motif based on the C-terminal sequence of
alpha-melanocyte-stimulating hormone.
AB - The C-terminal tripeptide of the alpha-melanocyte stimulating hormone (alpha
MSH11-13) possesses strong antiinflammatory activity without known cellular
target. In order to better understand the structural requirements for function of
such motif, we designed, synthesized and tested out Trp- and Tyr-containing
analogues of the alpha-MSH11-13. Seven alpha-MSH11-13 analogues were synthesized
and characterized for their binding to the melanocortin receptors recombinantly
expressed in insect (Sf9) cells, infected with baculovirus carrying corresponding
MC receptor DNA. We also tested these analogues on B16-F1 mouse melanoma cells
endogenously expressing the MC1 receptor for binding and for ability to increase
cAMP levels as well as on COS-7 cells transfected with the human MC receptors.
The data indicate that HS401 (Ac-Tyr-Lys-Pro-Val-NH2) and HS402 (Ac-Lys-Pro-Val
Tyr-NH2) selectively bound to the MC1 receptor and stimulated cAMP generation in
a concentration dependent way while the other Tyr- and Trp-containing alpha-MSH11
13 analogues neither bound to MC receptors nor stimulated cAMP. We have thus
identified new MC receptor binding motif derived from the C-terminal sequence of
alpha-MSH. The tetrapeptides have novel properties as the both act via MC-ergic
pathways and also carry the anti-inflammatory alpha-MSH11-13 message sequence.
PMID- 17040214
TI - Mitochondrial uncoupling by the sulindac metabolite, sulindac sulfide.
AB - Sulindac is a non-steroidal antiinflammatory drug (NSAID) known to inhibit
cyclooxygenases (COX) 1 and 2, and at present of interest for cancer prevention.
However, its therapeutic use has been limited by its toxicity to the
gastrointestinal tract and liver. We address the effects of sulindac, of the
pharmacologically inactive metabolite, sulindac sulfone, and of the
pharmacologically active metabolite, sudindac sulfide, on isolated rat liver
mitochondria and HepG2 cells. Sulindac sulfide, but not sulindac sulfone or
sulindac itself, caused mitochondrial uncoupling, released preaccumulated Ca2+
from the organelle, and decreased Hep-G2 cell viability in apparent association
with cell ATP depletion resulting from mitochondrial uncoupling-associated
membrane potential dissipation.
PMID- 17040215
TI - Effect of caffeine intake 12 or 24 hours prior to melatonin intake and CYP1A2*1F
polymorphism on CYP1A2 phenotyping by melatonin.
AB - Earlier evidence suggests that melatonin is almost exclusively metabolised by
CYP1A2 and could serve as a probe drug for CYP1A2 phenotyping. However, caffeine
inhibits the metabolism of melatonin by CYP1A2 and dietary caffeine could be a
potential confounder for the measurement of CYP1A2 activity with melatonin. We
undertook a 3-phase cross-over study in 12 healthy volunteers to examine whether
caffeine (200 mg single dose), taken 12 hr or 24 hr prior to melatonin intake,
would affect the results of CYP1A2 phenotyping results as assessed by a spot
sample melatonin concentration 1.5 hr after intake of 6 mg of melatonin orally.
In addition we examined the influence of the CYP1A2*1F polymorphism on the
phenotyping results by combining the present material with another 12 persons
from a previous study. Caffeine, co-administered 12 or 24 hr prior to melatonin
intake, did not have any significant effect on the 1.5 hr melatonin concentration
(P=0.086 for ANOVA), but in two volunteers about 4 times increase in melatonin
concentration was observed after caffeine intake 12 hr (but not 24 hr) before
phenotyping with melatonin. Also, individuals homozygous for the CYP1A2*1A allele
had clearly higher 1.5 hr melatonin concentration compared with the *1F/*1F or
the *1F/*1A genotypes. Abstinence from caffeine for 24 hr prior to melatonin
intake should be enough to overcome the possible confounding effect of caffeine
on the CYP1A2 phenotyping with melatonin. Also, melatonin may be a sensitive
probe to detect phenotypic differences with regard to CYP1A2*1F polymorphism.
Melatonin might be, thus, advantageous for CYP1A2 phenotyping compared to the
standard probe caffeine.
PMID- 17040216
TI - Increased susceptibility to phenytoin teratogenicity: excessive generation of
reactive oxygen species or impaired antioxidant defense?
AB - Phenytoin is a human and animal teratogen. Accumulating evidence suggests that
the teratogenicity is associated with a potential of phenytoin to cause embryonic
cardiac arrhythmia and resultant generation of toxic reactive oxygen species via
hypoxia-reoxygenation mechanisms. The A/J mouse is more susceptible to phenytoin
teratogenicity than other mouse strains. The aim of this study was to investigate
whether A/J mice have other antioxidant enzyme activities than C57BL/6J and CD-1
mice. Also, strain differences in phenytoin effects on embryonic heart rate and
rhythm were determined. Another objective was to determine whether a spin
trapping agent with capacity to capture reactive oxygen species alter the
developmental toxicity of phenytoin. Treatment with this agent resulted in a
marked decrease in phenytoin teratogenicity, which supports the idea that
reactive oxygen species are important mediators for the teratogenic action of
phenytoin. The A/J mice embryos were most susceptible to the adverse cardiac
effects of phenytoin and had the highest activity of superoxide dismutase and
glutathione peroxidase, while the activity of catalase was the same in embryos of
the three different strains. The high activities of antioxidant enzymes in the
A/J stain indicate that the sensitivity to develop malformations is caused by
excessive arrhythmia-related generation of reactive oxygen species rather than
impaired antioxidant defense.
PMID- 17040217
TI - Ranitidine in acute high-dose organophosphate exposure in rats: effect of the
time-point of administration and comparison with pyridostigmine.
AB - Weak and reversible inhibitors of cholinesterase, when co-administered in large
doses, can act in a protective manner against more potent inhibitors such as
organophosphates. The clinically widely used histamine type 2 (H2) receptor
blocker ranitidine is among H2 blockers the most potent inhibitor of
acetylcholinesterase but roughly three to four orders of magnitude less potent
than paraoxon (an irreversible organophosphate esterase inhibitor) or
pyridostigmine (a reversible carbamate esterase inhibitor). We have previously
shown that in vitro ranitidine confers some protection against inhibition of
cholinesterases by paraoxon and that in vivo it both increases the number of rats
surviving an acute paraoxon exposure and also protects to some degree the
cholinesterases from organophosphate inhibition. The purpose of the study was to
compare in a prospective non-blinded study, in a rat model of acute high-dose
paraoxon exposure, ranitidine with pyridostigmine either administered
simultaneously or 30 min. before exposure. There were 36 rats in each of the 5
groups. All substances were applied intraperitoneally. Additional analysis
included data from a similar experiment carried out in 2005, in which 54 rats
were exposed to paraoxon only (G1) and 54 to paraoxon+ranitidine simultaneously
(G2). All groups (except controls; G6 & G7) received 1 micro Mol paraoxon
(approximately LD75); groups 2-5 received in addition to paraoxon: G2: 50 micro
Mol ranitidine within 1 min. of paraoxon, G3: 1 micro Mol pyridostigmine within 1
min. of paraoxon, G4: 50 micro Mol ranitidine 30 min. before paraoxon, G5: 1
micro Mol pyridostigmine 30 min. before paraoxon. Groups 6 & 7 received only
ranitidine and pyridostigmine respectively, group G1 received only paraoxon.
Mortality was recorded at 30 min., 1, 2, 3, 4, 24 and 48 hr. Mortality data were
compared using Kaplan-Meier plots and logrank tests. No Bonferroni correction for
multiple comparisons was applied and an alpha < or = 0.05 was considered
significant. All statistical analysis was performed by using SPSS 12.0
statistical software (SPSS Inc., Chicago, IL, USA). Simultaneous administration
of ranitidine or pyridostigmine with paraoxon does not significantly affect
mortality. Pretreatment (30 min. before) with both ranitidine or pyridostigmine
statistically and significantly reduced mortality. When administered before
paraoxon, pyridostigmine is statistically significantly superior to ranitidine.
Both ranitidine and pyridostigmine are protective against acute paraoxon toxicity
provided they are administered before paraoxon. Pyridostigmine results are
statistically significantly superior to ranitidine (< or =0.05).
PMID- 17040218
TI - Zidovudine inhibits protein kinase C activity in human chronic myeloid (K562)
cells.
AB - In this paper we show that human erythroleukaemia (K562) cells exhibited a
significant inhibition of protein kinase C activity when cells were exposed to 40
micro M zidovudine in a time interval of 5-180 min., whereas prolonged treatment
(24 hr) was uneffective. The addition of an excess of thymidine (125:1, mol:mol),
in the cell suspension with or without zidovudine fully restored the protein
kinase C activity. Interestingly, either in cell homogenates and in commercially
purified rat brain protein kinase C, both zidovudine and its monophosphate
derivative, caused inhibition that was higher than in intact cells. This
inhibition reached a maximal value of 45% when zidovudine or zidovudine
monophosphate were incubated with the pure commercial enzyme and in this case the
addition of thymidine did not prevent the enzyme inhibition. The conclusions from
these data are that either zidovudine or zidovudine monophosphate interact
directly with the pure enzyme, causing inhibition, while in intact cells exposed
to the drug, zidovudine monophosphate appears to be the main metabolite
responsible for protein kinase C inhibition.
PMID- 17040219
TI - Protection of azidothymidine-induced cardiopathology in mice by mildronate, a
mitochondria-targeted drug.
AB - Azidothymidine, a nucleoside-analogue reverse transcriptase inhibitor (NRTI), is
a commonly used antiretroviral drug in AIDS treatment, however its use is limited
by severe toxic side effects due to its influence on mitochondria that result in
myopathy, particularly affecting the cardiac muscle. We suggest that effective
protection of azidothymidine-induced cardiopathology can be expected from drugs
that are capable of targeting mitochondria. Therefore the present study in mice
was carried out with mildronate, a cardioprotective drug of the aza-butyrobetaine
class, which previously has been shown to act as a highly potent protector of
mitochondrial processes. In our study, saline (control), azidothymidine (50
mg/kg), mildronate (50, 100 and 200 mg/kg), and azidothymidine + mildronate (at
the doses mentioned) were injected intraperitoneally daily in separate groups of
mice for two weeks. At the termination of the experiment, mice were sacrificed,
the hearts were removed and cardiac tissue was examined morphologically and
immunohistochemically. It was found that azidothymidine, compared to control and
mildronate groups, induced major morphologic changes in cardiac tissue, which
were manifestated as degeneration and inflammation. These changes were prevented
when mildronate was co-administered with azidothymidine. Mildronate also reduced
the azidothymidine-induced expression of nuclear factor kappaBp65 (NF-kappaBp65).
The obtained data demonstrate a high ability of mildronate of preventing
azidothymidine-induced cardiopathologic changes, and suggest mildronate's
indirect action on azidothymidine-caused oxidative stress reactions leading to
mitochondrial dysfunction. This offers a rational combination of mildronate with
azidothymidine or other anti-HIV drugs for beneficial application in AIDS
therapy.
PMID- 17040220
TI - Evaluation of novel fluorogenic substrates for the detection of glycosidases in
Escherichia coli and enterococci.
AB - AIMS: Enzyme substrates based on 4-methylumbelliferone are widely used for the
detection of Escherichia coli and enterococci in water, by detection of beta
glucuronidase and beta-glucosidase activity respectively. This study aimed to
synthesize and evaluate novel umbelliferone-based substrates with improved
sensitivity for these two enzymes. METHODS AND RESULTS: A novel beta-glucuronide
derivative based on 6-chloro-4-methylumbelliferone (CMUG) was synthesized and
compared with 4-methylumbelliferyl-beta-D-glucuronide (MUG) using 42 strains of
E. coli in a modified membrane lauryl sulfate broth. Over 7 h of incubation, the
fluorescence generated from the hydrolysis of CMUG by E. coli was over twice that
from MUG, and all of the 38 glucuronidase-positive strains generated a higher
fluorescence with CMUG compared with MUG. Neither substrate caused inhibition of
bacterial growth in any of the tested strains. Four beta-glucosidase substrates
were also synthesized and evaluated in comparison with 4-methylumbelliferyl-beta
D-glucoside (MU-GLU) using 42 strains of enterococci in glucose azide broth. The
four substrates comprised beta-glucoside derivatives of umbelliferone-3
carboxylic acid and its methyl, ethyl and benzyl esters. Glucosides of the
methyl, ethyl and benzyl esters of umbelliferone-3-carboxylic acid, were found to
be superior to MU-GLU for the detection of enterococci, especially after 18 h of
incubation, while umbelliferone-3-carboxylic acid-beta-D-glucoside was inferior.
However, the variability in detectable beta-glucosidase activity among the
different strains of enterococci in short-term assays using the three carboxylate
esters (7 h incubation) may compromise their use for rapid detection and
enumeration of these faecal indicator bacteria. CONCLUSIONS: The beta
glucuronidase substrate CMUG appears to be a more promising detection system than
the various beta-glucosidase substrates tested. SIGNIFICANCE AND IMPACT OF THE
STUDY: The novel substrate CMUG showed enhanced sensitivity for the detection of
beta-glucuronidase-producing bacteria such as E. coli, with a clear potential for
application in rapid assays for the detection of this indicator organism in
natural water and other environmental samples.
PMID- 17040221
TI - Isolation and characterization of a bacterial strain of the genus Ochrobactrum
with methyl parathion mineralizing activity.
AB - AIMS: To isolate and characterize a methyl parathion (MP)-mineralizing bacterium,
and to elucidate the degradative pathway of MP and localize the responsible
degrading genes. METHODS AND RESULTS: A bacterial strain, designated B2, capable
of mineralizing MP was isolated from the MP-polluted soil. Analysis of the 16S
rRNA gene sequence and phenotypic analysis suggested that strain B2 had a close
relationship with Ochrobactrum anthropi. B2 could totally degrade MP and four
metabolites [p-nitrophenol (PNP), 4-nitrocatechol (4-NC), 1,2,4-benzenetriol (BT)
and hydroquinone (HQ)] were identified by HPLC and gas chromatography-mass
spectrometry analyses. Plasmid curing of strain B2 resulted in the loss of
ability of B2 to degrade PNP, but not the ability to hydrolyse MP. CONCLUSIONS:
Ochrobactrum sp. B2 can mineralize MP rapidly via PNP, 4-NC, BT and HQ pathway.
B2 harbours a plasmid encoding the ability to degrade PNP, while MP-hydrolysing
activity is encoded on the bacterial chromosome. SIGNIFICANCE AND IMPACT OF THE
STUDY: This new bacterial strain (B2) capable of mineralizing MP will be useful
in a pure-culture remediation process of organophosphate pesticides and their
metabolites such as nitroaromatics.
PMID- 17040222
TI - Assessment of DNA damage and repair in Mycobacterium terrae after exposure to UV
irradiation.
AB - AIM: Ultraviolet (UV) irradiation for drinking water treatment was examined for
inactivation and subsequent dark and photo-repair of Mycobacterium terrae.
METHODS AND RESULTS: UV sources tested were low pressure (monochromatic, 254 nm)
and medium pressure (polychromatic UV output) Hg lamps. UV exposure resulted in
inactivation, and was followed by dark or photo-repair experiments. Inactivation
and repair were quantified utilizing a molecular-based endonuclease sensitive
site (ESS) assay and conventional colony forming unit (CFU) viability assay.
Mycobacterium terrae was more resistant to UV disinfection compared to many other
bacteria, with approximately 2-log reduction at a UV fluence of 10 mJ cm(-2) ;
similar to UV inactivation of M. tuberculosis. There was no difference in
inactivation between monochromatic or polychromatic UV lamps. Mycobacterium
terrae did not undergo detectable dark repair. Photo-repair resulted in recovery
from inactivation by approximately 0.5-log in less than 30 min for both UV lamp
systems. CONCLUSIONS: Mycobacterium terrae is able to photo-repair DNA damage
within a short timeframe. The number of pyrimidine dimers induced by UV light
were similar for Escherichia coli and M. terrae, however, this similarity did not
hold true for viability results. SIGNIFICANCE AND IMPACT OF THE STUDY: There is
no practical difference between UV sources for disinfection or prevention of DNA
repair for M. terrae. The capability of M. terrae to photo-repair UV damage
fairly quickly is important for wastewater treatment applications where
disinfected effluent is exposed to sunlight. Finally, molecular based assay
results should be evaluated with respect to differences in the nucleic acid
content of the test micro-organism.
PMID- 17040223
TI - Optimum melanin production using recombinant Escherichia coli.
AB - AIMS: A parametric study was conducted to define optimum conditions to achieve
high yields in the conversion of tyrosine to eumelanin (EuMel) using recombinant
Escherichia coli. METHODS AND RESULTS: Escherichia coli W3110 (pTrcMutmelA)
expressing the tyrosinase coding gene from Rhizobium etli and glucose-mineral
media were used to transform tyrosine into EuMel. Batch aerobic fermentor
cultures were performed to study the effect of temperature, pH and inducer
concentration (isopropyl-D-thio-galactopyranoside) on melanin production. Under
optimum conditions, 0.1 mmol l(-1) of isopropyl-D-thio-galactopyranoside,
temperature of 30 degrees C, and changing pH from 7.0 to 7.5 during the
production phase, a 100% conversion of tyrosine into EuMel is obtained.
Furthermore, tyrosine feeding allowed us to obtain the highest level (6 g l(-1))
of EuMel produced by recombinant E. coli reported until now. CONCLUSIONS: The
most important factors affecting melanin formation and hence influencing the rate
and efficiency in the conversion of tyrosine into EuMel in this system, are the
temperature and pH. SIGNIFICANCE AND IMPACT OF THE STUDY: Maximum theoretical
yield was obtained using a simple culture process and mineral media to convert
tyrosine (a medium value compound) into melanin, a high value compound. The
process reported here avoids the use of purified tyrosinase, expensive chemical
methods or the cumbersome extraction of this polymer from animal or plant
tissues.
PMID- 17040224
TI - Introduction of air in the anaerobic culture of Streptococcus pneumoniae serotype
23F induces the release of capsular polysaccharide from bacterial surface into
the cultivation medium.
AB - AIM: An approach to increase Streptococcus pneumoniae capsular polysaccharide
(CPS) in the culture medium during fed-batch cultivation in bioreactor. METHODS
AND RESULTS: Streptococcus pneumoniae serotype 23F was cultivated in a 5-l
bioreactor with nitrogen-sparging and followed by addition of air in the
stationary phase. The amount of CPS released in the supernatant progressively
increased under air sparging. The profile of cellular viability and optical
density was similar in both cultures. Immunoelectron microscopy showed that the
amount of tightly cell-bound CPS was higher in bacteria cultivated under nitrogen
than under air. CONCLUSIONS: The stress caused by the addition of air at the
stationary phase promoted a large increase of free CPS into the medium, as a
consequence of the morphologic change in the capsule. SIGNIFICANCE AND IMPACT OF
THE STUDY: The use of air in the stationary phase of the culture would greatly
simplify the subsequent downstream process, allowing CPS purification from the
supernatant. The direct consequence of this process improvement is the reduction
of vaccine production costs.
PMID- 17040225
TI - F+ RNA coliphage typing for microbial source tracking in surface waters.
AB - AIMS: The utility of coliphages to detect and track faecal pollution was
evaluated using South Carolina surface waters that exceeded State faecal coliform
standards. METHODS AND RESULTS: Coliphages were isolated from 117 surface water
samples by single agar layer (SAL) and enrichment presence/absence (EP/A)
methods. Confirmed F+ RNA coliphages were typed for microbial source tracking
using a library-independent approach. Concentrations of somatic coliphages using
37 and 44.5 degrees C incubation temperatures were found to be significantly
different and the higher temperature may be more specific for faecal
contamination. The EP/A technique detected coliphages infecting Escherichia coli
Famp in 38 (66%) of the 58 surface water samples negative for F+ coliphages by
the SAL method. However, coliphages isolated by EP/A were found to be less
representative of coliphage diversity within a sample. Among the 2939 coliphage
isolates tested from surface water and known source samples, 813 (28%) were found
to be F+ RNA. The majority (94%) of surface water F+ RNA coliphage isolates typed
as group I. Group II and/or III viruses were identified from 14 surface water
stations, the majority of which were downstream of wastewater discharges. These
sites were likely contaminated by human-source faecal pollution. CONCLUSIONS: The
results suggest that faecal contamination in surface waters can be detected and
source identifications aided by coliphage analyses. SIGNIFICANCE AND IMPACT OF
THE STUDY: This study supports the premise that coliphage typing can provide
useful, but not absolute, information to distinguish human from animal sources of
faecal pollution. Furthermore, the comparison of coliphage isolation methods
detailed in this study should provide valuable information to those wishing to
incorporate coliphage detection into water quality assessments.
PMID- 17040226
TI - Genetic variability of Campylobacter jejuni isolated from fresh and frozen
broiler carcasses.
AB - AIMS: The aim of this study was to determine the genetic variability of
Campylobacter jejuni isolates from poultry before and after freezing treatment in
order to identify genotypes that would survive the treatment. METHODS AND
RESULTS: C. jejuni was isolated from both fresh and frozen halves of the same
carcass after freezing for 2 or more than 20 days at -20 degrees C. From 36
carcasses, representing five unrelated flocks in Norway, a total of 209 isolates
were included in the study. Thirty-two of the isolates were recovered with a
qualitative method while the remaining 177 were isolated using a quantitative
method. Isolates were genotyped with fluorescent amplified fragment length
polymorphism using MfeI and BglII restriction enzymes. Nine different genotypes
were identified, however, one genotype was shown to be dominant in three
different flocks. This genotype and the dominant genotype of another flock were
found among isolates from fresh and frozen broiler halves. They were also shown
to be identical to genotypes frequently identified among strains isolated from
humans, cattle and poultry flocks in previous years. CONCLUSIONS: Freezing
treatment or isolation method appeared not to select for a particular genotype.
SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the present study indicate
that the freezing tolerance of strains is not genotype dependent.
PMID- 17040227
TI - Use of n-hexadecane as an oxygen vector to improve Phaffia rhodozyma growth and
carotenoid production in shake-flask cultures.
AB - AIMS: To identify beneficial oxygen vectors for Phaffia rhodozyma in liquid
cultures, and to evaluate their use to improve the oxygen transfer and carotenoid
production in the yeast cultures. METHODS AND RESULTS: Several liquid
hydrocarbons were tested as oxygen vectors for improving the yeast growth and
carotenoid production in shake-flask cultures of P. rhodozyma. While all nontoxic
organic liquids (Log P: > or =5.6) showed a positive effect, n-hexadecane was
proved to be the most beneficial for the yeast growth and carotenoid production.
The addition of 9% (v/v) n-hexadecane to the liquid medium at the time of
inoculation was found to be optimal, increasing the carotenoid yield by 58% (14.5
mg l(-1) vs 9.2 g l(-1) in the control) and the oxygen transfer rate (OTR) by
90%. CONCLUSIONS: The addition of n-hexadecane to shake-flask cultures of P.
rhodozyma significantly improved the oxygen transfer in culture, thus increasing
the carotenoid production. SIGNIFICANCE AND IMPACT OF THE STUDY: Use of organic
oxygen vectors such as n-hexadecane may be a simple and useful means for
enhancing oxygen transfer and carotenoid production in liquid fermentation of P.
rhodozyma.
PMID- 17040228
TI - Lipolytic activity of Antarctic cold-adapted marine bacteria (Terra Nova Bay,
Ross Sea).
AB - AIMS: The aim of this study was to investigate the lipolytic activity of cold
adapted Antarctic marine bacteria and, furthermore, the combined effect of some
environmental factors on this enzymatic process. METHODS AND RESULTS: Strains
were assayed for lipolytic activity on a basal medium amended with seven
individual fatty acid esters. A significant activity was observed for 148
isolates (95.5% of the total screened). The interactive effect of pH, temperature
and NaCl concentration on the substrates was tested for six representative
isolates, identified as Pseudoalteromonas, Psychrobacter and Vibrio. Differences
between strains according to NaCl and pH tolerances were observed. Only one
strain degraded the substrate more efficiently at 4 degrees C than at 15 degrees
C. CONCLUSIONS: Our findings demonstrate that the lipolytic activity of Antarctic
marine bacteria is rather variable, depending on culture conditions, and occurs
in a wide range of salt concentration and pH. SIGNIFICANCE AND IMPACT OF THE
STUDY: Isolation and characterization of bacteria that are able to efficiently
remove lipids at low temperatures will provide insight into the possibility to
use cold-adapted bacteria as a source of exploitable enzymes. Moreover, research
on the interactive effects of salt concentration, pH and temperature will be
useful to understand the true enzyme potentialities for industrial applications.
PMID- 17040229
TI - Degradation of naphthenic acids by sediment micro-organisms.
AB - AIMS: Naphthenic acids (NAs) are naturally occurring, linear and cyclic
carboxylic surfactants associated with the acidic fraction of petroleum. NAs
account for most of the acute aquatic toxicity of oil sands process-affected
water (OSPW). The toxicity of OSPW can be reduced by microbial degradation. The
aim of this research was to determine the extent of NA degradation by sediment
microbial communities exposed to varying amounts of OSPW. METHODS AND RESULTS:
Eleven wetlands, both natural and process-affected, and one tailings settling
pond in Northern Alberta were studied. The natural wetlands and process-affected
sites fell into two distinct groups based on their water chemistry. The extent of
degradation of a 14C-labelled monocyclic NA surrogate [14C-cyclohexane carboxylic
acid (CCA)] was relatively uniform in all sediments (approximately 30%) after 14
days. In contrast, degradation of a bicyclic NA surrogate [14C-decahydronaphthoic
acid (DHNA)] was significantly lower in non process-affected sediments.
Enrichment cultures, obtained from an active tailings settling pond, using
commercially available NAs as the sole carbon source, resulted in the isolation
of a co-culture containing Pseudomonas putida and Pseudomonas fluorescens.
Quantitative GC-MS analysis showed that the co-culture removed >95% of the
commercial NAs, and partially degraded the process NAs from OSPW with a resulting
NA profile similar to that from 'aged wetlands'. CONCLUSIONS: Exposure to NAs
induced and/or selected micro-organisms capable of more effectively degrading
bicyclic NAs. Native Pseudomonas spp. extensively degraded fresh, commercial NA.
The recalcitrant NAs resembled those found in process-affected wetlands.
SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that it may be
possible to manipulate the existing environmental conditions to select for a
microbial community exhibiting higher rates of NA degradation. This will have
significant impact on the design of artificial wetlands for water treatment.
PMID- 17040230
TI - Glutamate dehydrogenase activity in lactobacilli and the use of glutamate
dehydrogenase-producing adjunct Lactobacillus spp. cultures in the manufacture of
cheddar cheese.
AB - AIMS: The study was undertaken to investigate the occurrence of glutamate
dehydrogenase activity in different species of lactobacilli, and to determine, in
a series of cheese-making trials, the effects of glutamate dehydrogenase
producing adjunct cultures on sensory attribute development during the maturation
of cheddar cheese. METHODS AND RESULTS: The presence of dehydrogenase activity
with glutamate as substrate was monitored in cell lysates of >100 strains from 30
different species of lactobacilli using a qualitative colorimetric plate
screening assay. Activity was detectable in 25 of the 29 representative species
obtained from culture collections and in 12 of the 13 non-starter species
isolated from cheese. There were pronounced interspecies and strain differences
in the occurrence, level and pyridine nucleotide specificity of the glutamate
dehydrogenase activity detected. Among the non-starter lactobacilli the highest
frequency of enzyme occurrence and activity was detected in the Lactobacillus
plantarum isolates. The establishment of glutamate dehydrogenase-producing
adjunct strains in the predominant population of lactobacilli in the cheese curd
affected the formation of a number of volatile compounds in ripening cheddar
cheese, while the presence of Lact. plantarum strains, in particular, was
associated with an intensification and acceleration of aroma and flavour
development during the maturation period. CONCLUSIONS: Glutamate dehydrogenase
formation by lactobacilli is a strain-dependent metabolic attribute, and adjunct
cultures expressing the activity that are able to proliferate during cheese
ripening have a positive impact on the rate of development and the intensity of
cheddar cheese aroma and flavour development. SIGNIFICANCE AND IMPACT OF THE
STUDY: It has been demonstrated that some strains of glutamate dehydrogenase
producing lactobacilli have potential use as adjunct cultures to accelerate and
intensify aroma and flavour formation during the manufacture of cheddar and, by
analogy, other similar varieties of cheese. The importance of phenotypic
discriminative monitoring of the dominant lactobacilli present during ripening to
confirm adjunct establishment and population complexity was highlighted as was
the requirement to establish the metabolic attributes of the non-starter
population in uninoculated control cheeses in comparative trials.
PMID- 17040231
TI - Nitrogen-fixing chemo-organotrophic bacteria isolated from cyanobacteria-deprived
lichens and their ability to solubilize phosphate and to release amino acids and
phytohormones.
AB - AIMS: Cyanobacteria-deprived lichens of the species Canoparmelia caroliniana,
Canoparmelia crozalsiana, Canoparmelia texana, Parmotrema sancti-angeli and
Parmotrema tinctorum were screened for the presence of chemo-organotrophic
nitrogen-fixing bacteria. METHODS AND RESULTS: Fifty-three lichen samples
subjected to enrichment selection using a nitrogen-free minimal medium were
positive for acetylene reduction. Seventeen isolates, able to fix nitrogen,
belonged to Gamma-proteobacteria group and were identified as: Acinetobacter sp.,
Pantoea sp., Pseudomonas sp., Pseudomonas stutzeri, Serratia marcescens and
Stenotrophomonas maltophilia, according to 16S rRNA gene sequences and
biochemical tests. The excretion of amino acid and phytohormone and the ability
of mineral phosphate solubilization were determined in 14 isolates. All isolates
were able to release amino acids and 3-indoleacetic acid. About 64% of the
isolates solubilized phosphates and 30% released ethylene. CONCLUSIONS: These
data confirm sparse evidence from the literature on the occurrence of chemo
organotrophic nitrogen-fixing bacteria in cyanobacteria-deprived lichens; the
isolates presented physiologic features which might benefit the host if they are
expressed when the bacteria are harboured by lichens. SIGNIFICANCE AND IMPACT OF
THE STUDY: Chemo-organotrophic nitrogen-fixing bacteria were isolated from a high
percentage (72.6%) of cyanobacteria-deprived lichens. All isolates presented
important physiological characteristics, some of which are being described here
for the first time.
PMID- 17040232
TI - Interaction of Desulfovibrio desulfuricans biofilms with stainless steel surface
and its impact on bacterial metabolism.
AB - AIMS: To study the influence of some metallic elements of stainless steel 304 (SS
304) on the development and activity of a sulfate-reducing bacterial biofilm,
using as comparison a reference nonmetallic material polymethylmethacrylate
(PMMA). METHODS AND RESULTS: Desulfovibrio desulfuricans biofilms were developed
on SS 304 and on a reference nonmetallic material, PMMA, in a flow cell system.
Steady-state biofilms were metabolically more active on SS 304 than on PMMA.
Activity tests with bacteria from both biofilms at steady state also showed that
the doubling time was lower for bacteria from SS 304 biofilms. The influence of
chromium and nickel, elements of SS 304 composition, was also tested on a
cellular suspension of Des. desulfuricans. Nickel decreased the bacterial
doubling time, while chromium had no significant effect. CONCLUSIONS: The
following mechanism is hypothesized: a Des. desulfuricans biofilm grown on a SS
304 surface in anaerobic conditions leads to the weakening of the metal passive
layer and to the dissolution in the bulk phase of nickel ions that have a
positive influence on the sulfate-reducing bacteria metabolism. This phenomenon
may enhance the biocorrosion process. SIGNIFICANCE AND IMPACT OF THE STUDY: A
better understanding of the interactions between metallic surfaces such as
stainless steel and bacteria commonly implied in the corrosion phenomena which is
primordial to fight biocorrosion.
PMID- 17040233
TI - Screening and characterization of yeasts for xylitol production.
AB - AIMS: To discover novel naturally occurring xylitol producing yeast species with
potential for industrial applications. METHODS AND RESULTS: Exactly 274 strains
were cultivated on both solid and liquid screening medium with xylose as the sole
carbon resource. Five strains were selected on the basis of significant growth
and high degree of xylose assimilation. Their phylogenetic position was confirmed
by the PCR-RFLP and sequence analysis of the D1/D2 domain of the 5' end of the
large subunit rDNA gene (5'-LSU rDNA). Enzymatic analysis was conducted to
compare xylose metabolism in each strain. Candida guilliermondii Xu280 and
Candida maltosa Xu316 were found to have high xylose consumption rates and
xylitol yields in the batch fermentation under micro-aerobic condition. The
effect of the different media with high initial xylose concentration on
biosynthesis of xylitol by both strains was investigated. CONCLUSIONS: We have
identified Candida spp. strains, which exhibit high levels of xylitol production
from xylose suggesting that these may have potential for industrial applications.
SIGNIFICANCE AND IMPACTS OF THE STUDY: Microbial species are of importance for
xylitol production. Xylitol production involves complicated metabolic regulation
including xylose transport, production of key enzymes and cofactor regeneration.
Thus, screening of naturally occurring xylose-utilizing micro-organisms is a
viable and effective mean to obtain xylitol producing organisms with industrial
application. Moreover, the research on selected strains will contribute to a
better understanding of regulatory properties of xylose metabolism in different
yeasts.
PMID- 17040234
TI - Carbon : nitrogen : phosphorus ratios influence biofilm formation by Enterobacter
cloacae and Citrobacter freundii.
AB - AIMS: To test the effects of C : N : P ratio modification of a well-known
nutrient medium formulation, the Endo formulation on biofilm formation by
Enterobacter cloacae Ecl and Citrobacter freundii Cf1 in both single-species and
binary species biofilms. METHODS AND RESULTS: The C : N : P atom : atom ratio of
a well-known nutrient medium formulation, the Endo formulation, that has been
applied in fermentative biohydrogen studies, was modified to include two
different C concentrations, one containing 17.65 g l(-1) and the other 8.84 g l(
1) sucrose, each containing four different C : N : P ratios, two at higher C : N
: P ratios (334 : 84 : 16.8 and 334 : 84 : 3) and two at lower C : N : P ratios
(334 : 28 : 5.6 and 334 : 28 : 1). Attached cells were enumerated after
dislodging the biofilms that had formed on granular activated carbon (GAC). The
modified medium containing 17.65 g l(-1) sucrose and having a C : N : P ratio of
334 : 28 : 5.6 resulted in significantly (P < 0.05) higher counts of attached
cells for both single-species biofilms at 7.73 log(10) CFU g(-1) GAC and 9.3
log(10)CFU g(-1) GAC for Ent. cloacae Ecl and Cit. freundii Cf1, respectively,
and binary species biofilms at 8.2 log(10) CFU g(-1) GAC and 6.34 log(10) CFU g(
1) GAC for Ent. cloacae Ecl and Cit. freundii Cf1, respectively. Scanning
electron micrographs showed qualitative evidence that the 334 : 28 : 5.6 ratio
encouraged more complex and extensive biofilm growth for both single-species and
binary species biofilms. CONCLUSIONS: The differences in the attachment numbers
between the different ratios were found not to be a result of the individual
actions of the bacterial isolates involved but rather because of the effects of
the various C : N : P ratios. The 334 : 28 : 5.6 ratio showed significantly (P <
0.05) higher counts of attached cells for both single-species and binary species
biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicates that C : N :
P ratios should be a key consideration with regard to maximizing biofilm
formation in shake flask and fluidized bed bioreactor studies as well as
understanding fundamental factors affecting biofilm growth in natural
environments.
PMID- 17040235
TI - Addition of oxidizing or reducing agents to the reaction medium influences amino
acid conversion to aroma compounds by Lactococcus lactis.
AB - AIMS: The aim of this research was to investigate the impact of extracellular
redox potential (Eh) on amino acid conversion to aroma compounds by Lactococcus
lactis that is commonly used as a starter in the cheese industry. METHODS AND
RESULTS: The study was realized in vitro by incubating resting cells of L. lactis
in reaction media in which E(h) was modified by the addition of oxidizing or
reducing agents. Oxidative condition (+300 mV) favoured the production of
aldehydes and volatile sulfur compounds responsible for malty, floral, fruity,
almond and cabbage aroma. This production was mainly the result of a chemical
oxidation of the alpha-keto acids produced by amino acid transamination. In
contrast, reducing condition (-200 mV) stimulated the production of carboxylic
acids such as phenylacetic, methylthiopropionic and isovaleric acids, which
contribute to the very-ripened-cheese aroma as well as the production of hydroxy
acids. CONCLUSIONS: Eh of the medium highly influences the nature of aroma
compounds produced from amino acid catabolism by the resting cells of L. lactis.
SIGNIFICANCE AND IMPACT OF THE STUDY: E(h) is a parameter that is not controlled
during cheese production. Its control throughout cheese making and ripening could
permit control of aroma formation in cheese.
PMID- 17040236
TI - Human astroviruses in raw sewage samples in Hungary.
AB - AIMS: Routine procedures for monitoring viruses in water samples have not been
drawn up for the water-microbiology screening panel. Enteric viruses, including
astroviruses, are able to persist under environmental conditions and may cause
public health problems by contaminating natural and drinking water resources. The
aim of this study was to detect human astroviruses (HAstVs) from raw wastewater
samples. METHODS AND RESULTS: To obtain data on whether human astroviruses are
shed in the environment, 35 raw sewage samples from 22 sewage plants in different
regions of Baranya County, Hungary were tested for astrovirus using a
polyethylene glycol method for concentration and a guanidinium thiocyanate-silica
procedure for extraction of viral RNA. Reverse transcription-polymerase chain
reaction (RT-PCR) with HAstV-specific primer pairs was used for amplification and
the specificity of amplicons was confirmed by nucleotide sequencing and
phylogenetic analysis. Among the 35 raw sewage samples, 15 (43%) contained HAstV
and by sequence analysis, 10 genotype HAstV-1 and one genotype HAstV-2 were
identified. CONCLUSIONS: The high detection rate of astroviruses we encountered
in this study provide convincing evidence that HAstVs circulate at a relatively
high frequency in the Hungarian population. No correlation between the standard
indicators of faecal pollution and the presence of HAstVs was found. SIGNIFICANCE
AND IMPACT OF THE STUDY: Our study is the first report on detection of HAstV in
sewage in Hungary and suggests that HAstV might be potent indicators of viral
pollution in environmental specimens.
PMID- 17040237
TI - Genetic diversity and description of transmission routes for Campylobacter on
broiler farms by amplified-fragment length polymorphism.
AB - AIMS: To investigate the genetic diversity of Campylobacter in broilers and in
the environment of broiler farms, to compare the genetic profiles and describe
critical factors for transmission to broilers. METHODS AND RESULTS: Flocks at
three of four investigated farms became colonized with Campylobacter. The total
proportion of Campylobacter-positive samples at different farms varied from 20%
to 42%. The farm with the poorest biosecurity routines had broilers that became
infected earliest, the highest proportion of positive samples and the highest
genetic diversity among the broiler Campylobacter isolates. Campylobacter
isolates within common amplified-fragment length polymorphism (AFLP) clusters (95
100%) were found to be present in outdoor environment and in broilers at adjacent
farms before they were found in the broilers. A large presence of Campylobacter
in the farm environment was demonstrated after the broilers were infected. A high
genetic diversity was found among Campylobacter present in the outdoor
environment, where certain Campylobacter clusters were found for periods of up to
6 weeks. CONCLUSION: Confirmation by AFLP indicates adjacent poultry farms and
outdoor environment as major sources of Campylobacter infection of broilers, this
being the novel achievements. SIGNIFICANCE AND IMPACT OF THE STUDY: The results
provide more exact knowledge on transmission of Campylobacter at farm level,
helpful for developing optimal preventive strategies.
PMID- 17040238
TI - Combined effect of mild heat and acetic acid treatment for inactivating
Escherichia coli O157:H7, Listeria monocytogenes and Salmonella typhimurium in an
asparagus puree.
AB - AIMS: This study was conducted to validate combined heat and acid treatments for
inactivating Escherichia coli O157:H7, Listeria monocytogenes and Salmonella
typhimurium in an acidified brine containing, or pickled, asparagus model food.
METHODS AND RESULTS: A mixture of three strains of E. coli O157:H7, L.
monocytogenes and S. typhimurium were inoculated onto pickled asparagus samples.
Combinations of various concentrations of acetic acid [0%, 0.25%, 0.5%, 0.75%,
1%, 1.5% and 2% (v/v)] and various temperatures (40 degrees C, 50 degrees C, 60
degrees C and 75 degrees C) were investigated. Following treatment, asparagus
samples were stored at room temperature and enumerated at 0, 0.5, 1, 2 and 3
days. Heat and acetic acid treatments were synergistic. The inhibitory effects of
these combined treatments on the tested foodborne pathogens were also effective
during storage. Loss of green colour in the pickled asparagus significantly
increased with increasing concentrations of acetic acid. CONCLUSIONS: Using a
combination of mild heat and acetic acid treatments can successfully control E.
coli O157:H7, L. monocytogenes and S. typhimurium in pickled asparagus,
combinations of heat and acid are synergistic and effective treatments can be
selected to reduce adverse effect on colour which occur during product storage.
SIGNIFICANCE AND IMPACT OF THE STUDY: Mild heating plus acetic acid treatment are
synergistic, so combined treatments can be developed, which would lower the
temperature and amount of acetic acid required for minimally processed vegetables
while maintaining pathogen control.
PMID- 17040239
TI - Commensal bacilli inhibitory to mastitis pathogens isolated from the udder
microbiota of healthy cows.
AB - AIMS: To isolate from the microbiota of the healthy cow udder commensal bacteria
having antimicrobial activity against bovine mastitis pathogens, with a long-term
view to their potential application as antimastitis probiotics. METHODS AND
RESULTS: Bacterial isolates from four healthy cow udders were tested for
inhibitory activity against three Gram-positive indicator bacteria. This led to
the selection of nine broadly inhibitory strains. All were of the Bacillus genus
and their antimicrobial activities, which appeared heterogeneous on the basis of
their antibacterial spectra and heat susceptibilities, enabled grouping of the
inhibitory bacilli into six different inhibitory profiles. All displayed strong
in vitro activity against Gram-positive mastitis pathogens. Inhibitory bacilli
were recovered from each of the 11 udder samples collected over 7 months from one
of these cows and the isolates included representatives of all six inhibitory
profiles. CONCLUSIONS: Bacilli present in the udder microbiota of healthy cows
can produce a variety of broadly active inhibitors of Gram-positive bacteria,
including potential mastitis pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY:
Inhibitor-producing strains of commensal Bacillus species have been identified,
which may have the potential for use as possible antimastitis probiotics.
PMID- 17040240
TI - Mechanisms of killing of spores of Bacillus subtilis by dimethyldioxirane.
AB - AIMS: To determine the mechanisms of Bacillus subtilis spore resistance to and
killing by a novel sporicide, dimethyldioxirane (DMDO) that was generated in situ
from acetone and potassium peroxymonosulfate at neutral pH. METHODS AND RESULTS:
Spores of B. subtilis were effectively killed by DMDO. Rates of killing by DMDO
of spores lacking most DNA protective alpha/beta-type small, acid-soluble spore
proteins (alpha- beta- spores) or the major DNA repair protein, RecA, were very
similar to that of wild-type spore killing. Survivors of wild-type and alpha-
beta- spores treated with DMDO also exhibited no increase in mutations. Spores
lacking much coat protein due either to mutation or chemical decoating were much
more sensitive to DMDO than were wild-type spores, but were more resistant than
growing cells. Wild-type spores killed with this reagent retained their large
pool of dipicolinic acid (DPA), and the survivors of spores treated with DMDO
were sensitized to wet heat. The DMDO-killed spores germinated with nutrients,
albeit more slowly than untreated spores, but germinated faster than untreated
spores with dodecylamine. The killed spores were also germinated by very high
pressures and by lysozyme treatment in hypertonic medium, but many of these
spores lysed shortly after their germination, and none of these treatments were
able to revive the DMDO-killed spores. CONCLUSIONS: DMDO is an effective reagent
for killing B. subtilis spores. The spore coat is a major factor in spore
resistance to DMDO, which does not kill spores by DNA damage or by inactivating
some component needed for spore germination. Rather, this reagent appears to kill
spores by damaging the spore's inner membrane in some fashion. SIGNIFICANCE AND
IMPACT OF THE STUDY: This work demonstrates that DMDO is an effective
decontaminant for spores of Bacillus species that can work under mild conditions,
and the killed spores cannot be revived. Evidence has also been obtained on the
mechanisms of spore resistance to and killing by this reagent.
PMID- 17040241
TI - Degradation of mikan (Japanese mandarin orange) peel by a novel Penicillium
species with cellulolytic and pectinolytic activity.
AB - AIMS: The mikan, or Japanese mandarin orange, is a popular fruit in Japan, but
its peel is one of the major agricultural wastes. The aims of this study were to
screen, isolate, and characterize a mikan peel-degrading microbe. METHODS AND
RESULTS: Several samples including activated sludge, sediment, compost and
spoiled mikan peel were collected and cultured in a minimal salt medium
containing mikan peel as the sole carbon source. Degradation activity was found
in a culture of the spoiled mikan peel, and a fungal strain, designated OP1, with
both cellulolytic and pectinolytic activity was isolated. No toxic metabolites,
such as mycotoxins, were found in OP1 cultures, as evaluated by gas
chromatography/mass spectrometry. A phylogenetic analysis strongly suggested that
OP1 is a novel species of the genus Penicillium. CONCLUSIONS: Results suggest
that Penicillium sp. OP1 plays an important role in aerobic microbial degradation
of cellulose/pectin-rich biomasses in soil ecology, and further imply that this
strain may be useful for both simultaneous cellulase/pectinase production and
reduction of agricultural waste. SIGNIFICANCE AND IMPACT OF THE STUDY: The
present results advance our understanding of microbial degradation of
cellulose/pectin-rich biomasses in the natural environment, and offer a new tool
for reduction of agricultural waste, which is important for sustaining
circulatory societies.
PMID- 17040242
TI - Surface decontamination of beef inoculated with Salmonella Typhimurium DT104 or
Escherichia coli O157:H7 using dry air in a novel heat treatment apparatus.
AB - AIMS: To determine the effectiveness of a novel dry air decontamination apparatus
in the deactivation of Salmonella serotype Typhimurium DT104 or Escherichia coli
O157:H7 on beef surfaces. METHODS AND RESULTS: A laboratory scale dry air
decontamination apparatus, capable of producing repeatable and known heating time
temperature cycles on food surfaces was used in decontamination trials. Beef
samples were surface inoculated with 7-8 log10CFU cm(-2) of S. Typhimurium DT104
or E. coli O157:H7 and heated at 60, 75, 90 and 100 degrees C using fast and slow
heating rates and subsequently held at these temperatures for up to 600 s. A
substantial reduction in pathogen numbers was achieved at higher temperatures (90
and 100 degrees C, 4.18-6.06 log10CFU cm(-2)) using both heating rates, but cell
survival at these temperatures was also observed. At the lower temperatures,
deactivation was small at 60 degrees C in particular it was less than one log
unit after 3 min heating. No significant differences were observed when total
reductions in pathogen counts were compared for all the temperature/heat up time
combinations tested. During slow heating at 90 degrees C, and both heating rates
at 100 degrees C, the pattern of deactivation of S. Typhimurium DT104 or E. coli
O157:H7 was triphasic. CONCLUSIONS: This study has shown that heating meat
surfaces with dry air can achieve substantial reductions in S. Typhimurium DT104
or E. coli O157:H7. As surface decontamination of beef surfaces with dry air had
a negative effect on beef colour and appearance, such a decontamination apparatus
would be unsuitable for producing meat for retail sale but it could be used to
produce safer meat for use in the catering trade. SIGNIFICANCE AND IMPACT OF THE
STUDY: This study provides researchers and food processors with data on the
dynamic changes in S. Typhimurium DT104 and E. coli O157:H7 counts on intact beef
surfaces during heating with dry air under realistic (time-varying) temperature
conditions.
PMID- 17040243
TI - Campylobacter jejuni inactivation in New Zealand soils.
AB - AIM: The study was undertaken to determine the inactivation rate of Campylobacter
jejuni in New Zealand soils. METHODS AND RESULTS: Farm dairy effluent (FDE)
inoculated at c. 10(5) ml(-1) with C. jejuni was applied to intact soil cores at
a rate of 2 l m(-2). Four soils were used: Hamilton (granular); Taupo (pumice);
Horotiu and Waihou (allophanic). After FDE application cores were incubated at 10
degrees C for up to 32 days. For all four soils all the FDE remained within the
cores and at least 99% of C. jejuni were retained in the top 5 cm. Campylobacter
jejuni had declined to the limit of detection (two C. jejuni 100 g(-1)) by 25
days in Hamilton and Taupo soils and by 32 days in Waihou soil. In contrast, in
Horotiu soil the decline was only three orders of magnitude after 32 days.
Simulated heavy rainfall was applied 4 and 11 days after FDE application and only
about 1% of the applied C. jejuni were recovered in leachates. CONCLUSIONS: This
study demonstrated that at least 99% of applied C. jejuni were retained in the
top 5 cm of four soils where they survived for at least 25 days at 10 degrees C.
SIGNIFICANCE AND IMPACT OF THE STUDY: Soil retention of C. jejuni is efficient at
FDE application rates that prevent drainage losses. The low infectious dose of C.
jejuni and its ability to survive up to 25 days have implications for stock
management on dairy farms.
PMID- 17040245
TI - Zoonotic viral diseases and the frontier of early diagnosis, control and
prevention.
AB - Public awareness of the human health risks of zoonotic infections has grown in
recent years. Currently, concern of H5N1 flu transmission from migratory bird
populations has increased with foci of fatal human cases. This comes on the heels
of other major zoonotic viral epidemics in the last decade. These include other
acute emerging or re-emerging viral diseases such as severe acute respiratory
syndrome (SARS), West-Nile virus, Ebola virus, monkeypox, as well as the more
inapparent insidious slow viral and prion diseases. Virus infections with
zoonotic potential can become serious killers once they are able to establish the
necessary adaptations for efficient human-to-human transmission under
circumstances sufficient to reach epidemic proportions. The monitoring and early
diagnosis of these potential risks are overlapping frontiers of human and
veterinary medicine. Here, current viral zoonotics and evolving threats are
reviewed.
PMID- 17040246
TI - Pathogenesis and treatment of diabetic vascular disease - illustrated by two
cases.
AB - This publication is a summary of the presentations given at the First JIM Grand
Round held at the Sahlgrenska University Hospital on 15 March 2006. The Grand
Round was based on two case reports; a patient with type 2 diabetes and
pronounced macrovascular disease and another patient with early microvascular
disease combined with the macrovascular complications. The pathogenesis of the
vascular complications and the current treatment regimens were discussed in
relation to the history and examinations performed in these patients.
PMID- 17040247
TI - Right bundle branch block and long-term mortality in patients with acute
congestive heart failure.
AB - OBJECTIVES: Risk stratification in acute congestive heart failure (ACHF) is
poorly defined. The aim of the present study was to assess the impact of right
bundle brunch block (RBBB) on long-term mortality in patients presenting with
ACHF. METHODS AND RESULTS: The initial 12-lead electrocardiogram was analysed for
RBBB in 192 consecutive patients presenting with ACHF to the emergency
department. The primary endpoint was all-cause mortality during 720-day follow
up. This study included an elderly cohort (mean age 74 years) of ACHF patients.
RBBB was present in 27 patients (14%). Age, sex, B-type natriuretic peptide
levels and initial management were similar in patients with RBBB when compared
with patients without RBBB. However, patients with RBBB more often had pulmonary
comorbidity. A total of 84 patients died during follow-up. Kaplan-Meier analysis
revealed that mortality at 720 days was significantly higher in patients with
RBBB when compared with patients without RBBB (63% vs. 39%, P = 0.004). In Cox
proportional hazard analysis, RBBB was associated with a two-fold increase in
mortality (hazard ratio 2.18, 95% CI 1.26-3.66; P = 0.003). This association
persisted after adjustment for age and comorbidity. CONCLUSIONS: RBBB is a
powerful predictor of mortality in patients with ACHF. Early identification of
this high-risk group may help to offer tailored treatment in order to improve
outcome.
PMID- 17040248
TI - Increased levels of KL-6 and subsequent mortality in patients with interstitial
lung diseases.
AB - OBJECTIVES: KL-6 is a specific marker in patients with interstitial lung diseases
(ILDs); however, the relationship between elevated levels of KL-6 and subsequent
mortality is not well defined. To determine if elevated serum levels of KL-6 are
associated with increased mortality, and to identify the most suitable cut-off
level of KL-6 by which to distinguish between good prognosis and poor prognosis,
we evaluated the prognostic significance of serum KL-6 levels in patients with
stable-state ILDs. METHODS: Two hundred and nineteen patients diagnosed with ILDs
(152 with idiopathic interstitial pneumonia and 67 with collagen disease
associated pulmonary fibrosis) at Tsukuba University Hospital from April 1999 to
October 2005 were entered in this study. Serum KL-6 levels in patients with ILDs
were measured with a commercially available enzyme immunoassay kit, and these
patients were then followed up. RESULTS: During the follow-up period, 58 of the
219 patients died of respiratory failure. Patients who died during this period
had higher levels of KL-6 than did those who did not (P = 0.0004). The receiver
operating characteristic curve analysis showed 1000 U mL(-1) as the most suitable
cut-off level by which to distinguish between the two groups of patients. The 95%
specificity serum KL-6 level with poor outcome was 2750 U mL(-1). In univariate
and multivariate analysis, elevated serum KL-6 (>1000 U mL(-1)) in the stable
state indicated poor prognosis (P = 0.0005, log-rank test; P = 0.0001, Cox
proportional hazard model). CONCLUSIONS: Elevated KL-6 level may provide simple,
yet valuable information by which to identify patients with ILDs who are at
increased risk for subsequent mortality.
PMID- 17040249
TI - Characteristics and outcome amongst young adults suffering from out-of-hospital
cardiac arrest in whom cardiopulmonary resuscitation is attempted.
AB - OBJECTIVES: Amongst patients suffering from out-of-hospital cardiac arrest, young
adults represent a minority. However, these victims suffer from the catastrophe
when they are in a very active phase of life and have a long life expectancy.
This survey aims to describe young adults in Sweden who suffer from out-of
hospital cardiac arrest and in whom cardiopulmonary resuscitation (CPR) is
attempted in terms of characteristics and outcome. DESIGN: Prospective and
descriptive design. SUBJECTS AND METHODS: Young adults (18-35 years) who suffered
from out-of-hospital cardiac arrest in whom CPR was attempted and who were
included in the Swedish Cardiac Arrest Registry between 1990 and 2004. MAIN
OUTCOME MEASURES: Survival to 1 month. RESULTS: In all, 1105 young adults (3.1%
of all the patients in the registry) were included, of which 29% were females,
51% were nonwitnessed and 15% had a cardiac aetiology. Only 17% were found in
ventricular fibrillation, 53% received bystander CPR. The overall survival to 1
month was 6.3%. High survival was found amongst patients found in ventricular
fibrillation (20.8%) and those with a cardiac aetiology (14.8%). Ventricular
fibrillation at the arrival of the rescue team remained an independent predictor
of an increased chance of survival (odds ratio: 7.43; 95% confidence interval:
3.44-16.65). CONCLUSION: Amongst young adults suffering from out-of-hospital
cardiac arrest and in whom CPR was attempted, a minority survived to 1 month.
Subgroups with a higher survival could be defined (patients found in ventricular
fibrillation and patients in whom there was a cardiac aetiology). However, only
one independent predictor of an increased chance of survival could be
demonstrated, i.e. ventricular fibrillation at the arrival of the rescue team.
PMID- 17040250
TI - Prospective study of body size and risk for stroke amongst women below age 60.
AB - The relation between obesity, particularly abdominal obesity, and risk of stroke
amongst women remains unclear. In 1991-1992, a prospective study was initiated in
Sweden amongst women who returned a self-administered questionnaire. Through
linkage with nation-wide registries, 45,449 women, free of stroke at entry, were
followed up until diagnosis of first incident stroke, death, or the end of follow
up in 2002. We estimated multivariate relative risks (RRs) with 95% confidence
intervals (CIs) from Cox proportional hazards regression models. A total of 170
incident stroke cases occurred during an average of 11 years of follow-up. The RR
of stroke amongst women in the highest compared with the lowest quintile was 2.4
(95% CI 1.3-4.2; P for trend 0.04) for waist-to-hip ratio, 2.5 (95% CI 1.5-4.3; P
for trend 0.01) for waist-to-height ratio and 2.3 (95% CI 1.2-4.3; P for trend
0.02) for waist circumference. Adjustment for hypertension and diabetes
attenuated these risk estimates. In contrast, birth weight, body mass index (BMI)
at age 18, BMI at entry, weight change in adulthood and adult height were not
significantly associated with risk of stroke. This study provides evidence that,
in contrast to BMI, several different measures of abdominal obesity are strong
predictors of stroke in women.
PMID- 17040251
TI - Antipsychotics and risk of first-time hospitalization for myocardial infarction:
a population-based case-control study.
AB - BACKGROUND: Use of antipsychotics has been linked with an adverse cardiovascular
risk factor profile and an increased risk of dysrhythmia and sudden cardiac
death. However, detailed data on the association between use of antipsychotics
and development of atherosclerotic disease are limited. OBJECTIVE: To examine
risk of hospitalization for myocardial infarction (MI) amongst users of
antipsychotics compared with non-users. DESIGN AND SUBJECTS: A population-based
case-control study using data from hospital discharge registries in the counties
of North Jutland, Viborg and Aarhus, Denmark, and the Danish Civil Registration
System. We identified 21,377 cases of first-time hospitalization for MI and
106,885 sex- and age-matched non-MI population controls in the period 1992-2004.
All prescriptions for antipsychotics filled prior to the date of admission for MI
were retrieved from population-based prescription databases. We used conditional
logistic regression to adjust for a wide range of covariates. RESULTS: Current
users of atypical [adjusted relative risk: 0.98, 95% confidence interval (CI):
0.88-1.09] and typical antipsychotics (adjusted relative risk: 0.99, 95% CI: 0.96
1.03) had no increased overall risk of being admitted to hospital for MI when
compared with non-users of antipsychotics. These findings were consistent in all
examined subgroups. Further, we found no association between the cumulative dose
of antipsychotics and the risk of hospitalization for MI. CONCLUSION: These
findings do not support the hypothesis that use of antipsychotics and in
particular atypical antipsychotics is associated with increased risk of MI.
PMID- 17040252
TI - A simple diagnostic strategy in hospitalized patients with clinically suspected
pulmonary embolism.
AB - OBJECTIVES: Diagnostic strategies in patients with suspected pulmonary embolism
have been extensively studied in outpatients; their value in hospitalized
patients has not been well established. Our aim was to determine the safety and
clinical utility of a simple diagnostic strategy in hospitalized patients with
suspected pulmonary embolism. DESIGN: Prospective management study. SETTING:
Twelve teaching hospitals (five academic, seven general hospitals). SUBJECT: A
total of 605 hospitalized patients with clinically suspected pulmonary embolism.
All patients completed the study. INTERVENTIONS: First the clinical decision rule
(CDR)-score was calculated. An unlikely CDR-score in combination with a normal D
dimer excluded pulmonary embolism. All other patients underwent helical computed
tomography (CT). CT either diagnosed or excluded pulmonary embolism, in which
case anticoagulants were started or withheld. All patients were instructed to
report symptoms of venous thrombosis. Objective tests were performed to confirm
venous thromboembolism. The primary outcome was the incidence of symptomatic
venous thrombosis during 3-month follow-up. RESULTS: The combination of an
unlikely CDR-score and a normal D-dimer excluded pulmonary embolism in 60
patients (10% of all patients); no venous thromboembolic event occurred during
follow-up (0%; 95% CI 0-6.7%). CT excluded pulmonary embolism in 380 patients;
during follow-up venous thromboembolism occurred in five patients (1.4%; 95% CI
0.4-3.1%). CONCLUSIONS: An unlikely CDR-score in combination with a normal D
dimer appears to exclude pulmonary embolism safely in hospitalized patients.
Before clinical implementation it is important this safety is confirmed by
others. CT testing was obviated in only 10% of patients. CT can safely exclude
pulmonary embolism in hospitalized patients.
PMID- 17040253
TI - The impact of gender on survival amongst patients with implantable cardioverter
defibrillators for primary prevention against sudden cardiac death.
AB - BACKGROUND: Implantable cardioverter defibrillators (ICDs) are a life-saving
therapy for many patients with cardiovascular disease at increased risk of fatal
dysrhythmias. As men comprise the majority of the study population (67-92%) in
clinical trials, the benefit to women is unknown. We performed a meta-analysis of
primary prevention trials to evaluate the impact of ICDs in men and women on
death from any cause. METHODS: Included trials met the following criteria: (i)
randomized controlled trials versus standard of care, (ii) ICD used as primary
prevention in a well-described protocol and (iii) data provided on risk of death
from any cause for both male and female patients. RESULTS: Five clinical trials
were included in this meta-analysis. The risk of death from any cause was
significantly reduced by 26% in male patients who received ICD therapy compared
to control, hazard ratio (HR) 0.74 (95% CI 0.60-0.91) but not amongst female
patients, HR 0.81 (95% CI 0.60-1.09). As the COMPANION trial evaluated the
combination of biventricular pacemaker with ICD therapy we conducted a separate
analysis without the inclusion of this study. Male patients receiving ICD therapy
demonstrated a similar 24% reduction in risk of death from any cause, HR 0.76
(95% CI 0.58-0.99) whilst female patients demonstrated a reduction of only 12%,
HR 0.88 (95% CI 0.63-1.22). CONCLUSIONS: Unlike their male counterparts, females
did not significantly benefit from ICD therapy and without concurrent
biventricular pacing, appear only to achieve a nonsignificant 12% reduction in
risk of death.
PMID- 17040254
TI - Low plasma adiponectin is associated with coronary artery disease but not with
hypertension in high-risk nondiabetic patients.
AB - OBJECTIVE: To investigate the association of plasma adiponectin levels with
coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance
(IR) in nondiabetic Caucasian patients. DESIGN: We measured plasma adiponectin
levels, IR (HOMA index), and the CAD atherosclerotic burden (angiography-based
modified Duke Index score) in 400 nondiabetic patients undergoing coronary
angiography. HT was diagnosed by the European Society of Hypertension/European
Society of Cardiology (ESH/ESC) guidelines or if patients were on
antihypertensive treatment. RESULTS: Coronary artery disease was found in 62% of
the patients and ruled out in the rest (non-CAD group). Plasma adiponectin levels
were inversely related to the CAD score (beta = -0.12, P = 0.029) and predicted
the coronary atherosclerotic burden independent of other cardiovascular risk
factors. However, they were similar in NT and HT and showed no correlation with
blood pressure values. In non-CAD, but not in CAD patients, they were lower in
patients with than without IR (8.3 +/- 1.2 vs. 11.3 +/- 1.3, respectively; P =
0.007). CONCLUSIONS: In nondiabetic high-risk Caucasian patients plasma
adiponectin levels are inversely related to CAD severity and IR; however, they
are not strongly related to blood pressure values.
PMID- 17040256
TI - Efficacy or effectiveness?
PMID- 17040255
TI - HER-2 overexpression and targeted treatment by trastuzumab in a very old patient
with gastric cancer.
PMID- 17040258
TI - A qualitative study to assess the effectiveness of laser epilation using a
quality-of-life scoring system.
AB - BACKGROUND: Facial hirsutism has a negative effect on the quality of life (QOL)
of female patients. AIM: To assess the efficacy of laser epilation on the quality
of life in hirsute women. METHODS: Over a 6-month period, we recruited 38
patients with severe pathological facial hirsutism. Each patient completed a
pretreatment questionnaire consisting of a modified Dermatology Life Quality
Index (DLQI), a visual analogue scoring system, and an 'out-of-10' scoring
system. The patients were also scored independently by a doctor and a nurse. Each
patient received a laser-epilation treatment programme and was reassessed in an
identical fashion. RESULTS: Following laser epilation, the mean patient DLQI
score fell by 5 points. All three scoring groups scored lower across all scoring
methods following laser treatment. There was also correlation in scoring between
disciplines. CONCLUSION: DLQI provides a valid scoring system to assess the
efficacy of laser epilation. The interdisciplinary scores in this study indicate
that an objective grading system for facial hirsutism could be developed in the
future.
PMID- 17040259
TI - Preliminary testing for normality: some statistical aspects of a common concept.
AB - BACKGROUND: Statistical methodology has become an increasingly important topic in
dermatological research. Adequacy of the statistical procedure depends among
others on distributional assumptions. In dermatological articles, the choice
between parametric and nonparametric methods is often based on preliminary
goodness-of-fit tests. AIM: For the special case of the assumption of normally
distributed data, the Kolmogorov-Smirnov test is the most popular choice. We
investigated the performance of this test on four types of non-normal data,
representing the majority of real data in dermatological research. METHODS:
Simulations were run to assess the performance of the Kolmogorov-Smirnov test,
depending on sample size and severity of violations of normality. RESULTS: The
Kolmogorov-Smirnov test performs badly on data with single outliers, 10% outliers
and skewed data at sample sizes < 100, whereas normality is rejected to an
acceptable degree for Likert-type data. CONCLUSION: Preliminary testing for
normality is not recommended for small-to-moderate sample sizes.
PMID- 17040261
TI - Glomeruloid haemangioma with cerebriform morphology in a patient with POEMS
syndrome.
AB - A 40-year-old Chinese man presented with sensorimotor polyneuropathy, IgAlambda
paraprotein, osteosclerotic bone lesions, hypertrichosis, and impotence with
decreased testosterone and raised prolactin level. POEMS (polyneuropathy,
organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome
was diagnosed and he was treated with melphalan and prednisolone. After
chemotherapy, other manifestations of POEMS syndrome developed, such as multiple
haemangiomas over the chest and neck region, splenomegaly and generalized oedema.
One haemangioma had a peculiar clinical morphology, similar to the appearance of
cerebral gyri. Skin biopsy confirmed the diagnosis of glomeruloid haemangioma.
Chemotherapy was then switched to cyclophosphamide and prednisolone, resulting in
further improvement in muscle power and hypertrichosis. To our knowledge, this is
the first report on a clinically distinctive morphology of glomeruloid
haemangioma, and its recognition may increase the index of suspicion for early
skin biopsy.
PMID- 17040260
TI - Psychosomatic cofactors and psychiatric comorbidity in patients with chronic
itch.
AB - BACKGROUND: While psychosomatic factors may be involved in eliciting as well as
coping with chronic itch, psychiatric comorbidity often goes unrecognized in
dermatological patients. AIM: To record psychiatric illness, psychiatric and
psychotherapeutic pretreatment, and psychotherapy indication in dermatology
inpatients with pruritus. METHODS: A consecutive sample of 109 dermatology
inpatients with the symptom of pruritus were examined by interviews with
consecutive ratings by experts (using psychiatric ICD-10 diagnoses, the Global
Assessment of Functioning Scale and the Impairment Score) and self-assessment
using the the Eppendorf Itch Questionnaire. RESULTS: In > 70% of the pruritus
patients, 1-6 psychiatric diagnoses could be demonstrated. In > 60%,
psychotherapeutic or psychiatric treatment was recommended. In contrast, almost
90% of the patients had had no previous psychotherapeutic experience. CONCLUSION:
As psychiatric comorbidity in dermatology inpatients suffering from chronic itch
is high, dermatology departments should aim for an improvement of their
psychosomatic consultation and liaison services.
PMID- 17040262
TI - Unilateral naevoid trichoepitheliomas on the face of a child.
AB - Trichoepitheliomas are benign epidermal appendage tumours that present most
commonly as solitary lesions, and less often as multiple, symmetrically
distributed lesions on the face, scalp, neck and trunk. Only a few patients have
been reported in whom trichoepitheliomas were found as unusually configured
linear or plaque-like confluent lesions, all of which occurred in patients with
skin types V or VI. We describe a white girl with a hemifacial plaque of
confluent naevoid trichoepitheliomas, the first report of such lesions in a white
patient.
PMID- 17040263
TI - Generalized essential telangiectasia with conjunctival involvement.
AB - Generalized essential telangiectasia (GET) is a rare skin disorder characterized
by generalized development of dilated venules, which start at the lower
extremities and progressively spread to the rest of the body. Mucous and
conjunctival involvement is rare. The diagnosis is based on clinical examination,
after excluding other primary and secondary causes of telangiectasia.
PMID- 17040264
TI - Expression of adhesion molecules in atopic dermatitis is reduced by tacrolimus,
but not by hydrocortisone butyrate: a randomized immunohistochemical study.
AB - Topical tacrolimus represents an effective and well-tolerated treatment for
atopic dermatitis (AD). Its known effects include reduced production of
proinflammatory cytokines and reduced chemokine gradient. We performed lesional
skin biopsies on adult patients affected by moderate-to-severe AD. Then, patients
were randomized to receive local treatment with tacrolimus ointment 0.1% and
hydrocortisone butyrate ointment 1%. On the 21st day of treatment, another skin
specimen was taken. Nine patients treated with tacrolimus and seven treated with
hydrocortisone successfully concluded the trial. By immunohistochemistry
(alkaline phosphatase/antialkaline phosphatase method), we demonstrated that
endothelial leucocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule
(VCAM)-1 and intercellular adhesion molecule (ICAM)-1 showed different
intensities and patterns of expression in untreated AD lesions. Tacrolimus
treated specimens featured a significant reduction of the expression of ELAM-1,
VCAM-1 and ICAM-1, while hydrocortisone-treated lesions did not. Inhibition of
adhesion molecule expression may represent another selective mechanism of action
of topical tacrolimus in AD.
PMID- 17040265
TI - Depression accompanying compensatory hyperhidrosis following endoscopic thoracic
sympathectomy.
PMID- 17040266
TI - Hydrous ointment: potential confusion.
PMID- 17040267
TI - Basal cell carcinoma arising in a tattoo.
PMID- 17040268
TI - Oropharyngeal mycosis fungoides.
PMID- 17040269
TI - Treatment of mycosis fungoides with imiquimod 5% cream.
PMID- 17040270
TI - Treatment of chronic erythema nodosum with infliximab.
PMID- 17040271
TI - A case of isolated axillary hyperhidrosis successfully treated topically with 1%
glycopyrronium cream.
PMID- 17040272
TI - Second cite.
PMID- 17040273
TI - Pruritic papules on the trunk of a 67-year-old man.
PMID- 17040274
TI - An unusual tongue.
PMID- 17040275
TI - QT interval prolongation and beyond.
PMID- 17040276
TI - Magnitude of error introduced by application of heart rate correction formulas to
the canine QT interval.
AB - BACKGROUND: Accurate detection of drug-induced QT interval changes is often
confounded by concurrent heart rate changes. Application of heart rate correction
formulas has been the traditional approach to account for heart rate-induced QT
interval changes, and thereby identify the direct effect of the test article on
cardiac repolarization. Despite numerous recent studies identifying the
imprecision of these formulas they continue to be applied. METHODS: Using a
chronic atrioventricular dissociated His-paced canine model, heart rate
correction methods were evaluated for their ability to generate a corrected QT
interval independent of original heart rate. Additionally, His bundle pacing at a
heart rate of 60 beats/min allowed calculation of the magnitude of error
introduced by application of heart rate correction formulas. RESULTS: Of the
fixed parameter heart rate correction formulas, only Van de Water was able to
predict corrected QT values independent of the original heart rate. The magnitude
of error discovered by application of heart rate correction formulas varied, but
in many cases was very large. Bazett's formula was associated with a mean
overcorrection of 67.9 ms; Fridericia's 28.7 ms. Van de Water was the best fixed
parameter formula with a mean error of 10.8 ms. As expected, group and individual
corrections derived from linear regression of the HR-QT data offered improvement
over the traditional formulas. Both were able to predict QTc values independent
of the heart rate. However, errors of the magnitude of 10 and 6 ms, respectively,
were still introduced. CONCLUSION: Van de Water and linear regression correction
methods were superior to others in this study, but all methods generated QTc
errors equal to or much greater than the magnitude of interest for drug safety
evaluation.
PMID- 17040277
TI - Correlation between beat-to-beat QT interval variability and impaired left
ventricular function in patients with previous myocardial infarction.
AB - BACKGROUND: Beat-to-beat QT interval variability (QTV) is associated with sudden
cardiac death and New York Heat Association functional class severity. We sought
to evaluate the relationship between QTV and left ventricular (LV) function in
patients with previous myocardial infarction (MI). METHODS: Fifty-nine patients
with previous anterior MI were enrolled. LV ejection fraction (EF), LV end
systolic volume index (LVESVI), and LV end-diastolic volume index (LVEDVI) were
measured by LV contrast angiography. QT interval was measured by automated
analysis of 512-beat records of 12-lead electrocardiogram. The mean interval,
standard deviation and variance in RR and QT intervals, and the QT variability
index (QTVI) were calculated for each patient using two leads that corresponded
with and without the infarction site. High-frequency power, low-frequency power,
total-frequency power, and the ratio of low-frequency to high-frequency power in
RR and QT intervals were calculated. RESULTS: While measured indices of RR
intervals and indices of QT intervals, which did not correspond with the
infarction site, did not correlate with differences in LV function, measured
indices of QT intervals, which corresponded with the infarction site, did
correlate with differences in LV function. However, there were no correlations
between the ratio of low-frequency to high-frequency power in QT intervals and EF
or LVEDVI. Correlations between QTVI and LV function were observed, particularly
between QTVI and LVESVI (r = 0.712, P < 0.0001). CONCLUSION: In patients with
previous anterior MI, there was variability in temporal dispersion of QT interval
and a strong correlation between QTV corresponded with the infarcted site and LV
function.
PMID- 17040278
TI - Heart rate variability in young women with polycystic ovary syndrome.
AB - BACKGROUND: Limited data are available related to the effects of sex hormones on
cardiac autonomic function. Few studies investigated the heart rate variability
(HRV) parameters during regular menstrual cycle or in postmenopausal women using
hormone replacement therapy, but the results were contradictory. The aim of the
study was to compare the characteristics of the autonomic innervation of the
heart in polycystic ovary syndrome (PCOS) patients with regularly cycling
controls. METHODS: Thirty PCOS patients and 30 healthy regularly cycling controls
were included in the study. Groups were compared with respect to age and various
cardiovascular risk factors. Characteristics of autonomic innervation of the
heart were evaluated with HRV. Power spectral analysis of HRV was performed to
calculate the low frequency peak (LF 0.04-0.15 Hz), high-frequency peak (HF 0.15
0.40 Hz), LF in normalized unit (LF nu), HF in normalized unit (HF nu) and LF/HF
ratio. RESULTS: PCOS patients had adverse cardiovascular risk profile than
controls. As the HRV parameters, PCOS patients had significantly higher LF nu (P
= 0.005) and LF/HF ratio (P = 0.001) and significantly lower HF (P = 0.006) and
HF nu (P < 0.001) compared to controls. CONCLUSION: Autonomic innervation of the
heart can be affected in PCOS with increased sympathetic and decreased
parasympathetic components of HRV. As a result, sympathetic to parasympathetic
ratio may increase in PCOS. This finding should be confirmed with larger studies
also evaluating the clinical implications of altered HRV parameters.
PMID- 17040279
TI - Uncomplicated metabolic syndrome is associated with prolonged
electrocardiographic QTc interval and QTc dispersion.
AB - AIM: Metabolic syndrome is associated with increased risk of mortality and
morbidity. The present study evaluates the repolarization abnormalities in
patients with uncomplicated metabolic syndrome measuring corrected QT interval
(QTc) and corrected QT dispersion (QTd) on electrocardiogram. METHODS: The study
involved 83 subjects. A total of 50 individuals met criteria of metabolic
syndrome (Group A: 11 men, 39 women, mean body mass index (BMI) 36.7 kg/m2, mean
waist circumference 117.3 cm). And 33 participants were healthy normal volunteers
(Group B: 9 men, 24 women, mean BMI 21.3 kg/m2, mean waist circumference 76.2
cm). The two groups were matched for age and sex. Metabolic syndrome was
diagnosed according to the Adult Treatment Panel III criteria. The QTc intervals
and QTd were measured. RESULTS: Patients with uncomplicated metabolic syndrome
had significantly higher values of QTc-min, QTc-max, and QTd than control group
(P < 0.001). CONCLUSION: Patients with uncomplicated metabolic syndrome have a
greater dispersion of ventricular repolarization time and increased QTc-min and
QTc-max.
PMID- 17040280
TI - Reproducibility of computerized measurements of QT interval from multiple leads
at rest and during exercise.
AB - BACKGROUND: Accurate measurement of the QT interval is important for diagnosing
long QT syndrome (LQTS), and in research on determinants of ventricular
repolarization time. We tested automatic analysis of QT intervals from multiple
ECG leads on chest. METHODS: Eleven healthy volunteers and 10 genotyped LQTS
patients were tested at rest and during exercise with a bicycle ergometer twice 1
31 months apart. Electrocardiograms were recorded with the body surface potential
mapping system, and 12 precordial channels were selected for analysis. Averaged
QT peak and QT end intervals were determined with an automated algorithm, and the
difference QT end minus QT peak (Tp-e) was calculated. Repeatability was assessed
by coefficient of variation (CV) between measurements. RESULTS: Within one test
at rest the QT end intervals were highly repeatable with CV 0.6%. In repeated
tests CV was 4.4% for QT end interval and 3.5% when the QT interval was corrected
for heart rate. In exercise test at specified heart rates, mean CV was 3.0% for
QT end and 2.9% for QT peak interval. The CV of Tp-e interval was 10.2% at rest,
and 9.3% in exercise test. Reproducibility was comparable between healthy
subjects and LQTS patients. CONCLUSIONS: The BSPM system with automated analysis
produced accurate and highly repeatable QT interval measurements. Reproducibility
was adequate also over prolonged time periods both at rest and in exercise stress
test. The method can be applied in studying duration of ventricular
repolarization time in different physiologic and pharmacologic interventions.
PMID- 17040281
TI - Electrocardiographic predictors of arrhythmic death.
PMID- 17040282
TI - History of Wolff-Parkinson-White syndrome: introductory note to a classic article
by Louis Wolff, MD, John Parkinson, MD, and Paul D White, MD.
PMID- 17040283
TI - Bundle-branch block with short P-R interval in healthy young people prone to
paroxysmal tachycardia. 1930.
PMID- 17040284
TI - Wide QRS tachycardia: what is the rhythm?
AB - We report a case of an elderly man who presented to the emergency room
complaining of palpitations. Electrocardiogram revealed wide QRS tachycardia with
a narrow beat within the tachycardia. Most commonly, a narrow complex beat during
a wide complex tachycardia suggests a capture or fusion beat in the setting of
ventricular tachycardia. However, there are situations where supraventricular
tachycardia can also manifest this way. In our patient a pacemaker interrogation
clarified the diagnosis.
PMID- 17040286
TI - Molecular tumor markers for asbestos-related mesothelioma: serum diagnostic
markers.
AB - Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually
associated with previous exposure to asbestos. The incubation period of the tumor
may be described as 30-40 years, and the prognosis is dismal. In addition to
immunohistochemical markers, recently, serum markers for the diagnosis of
mesothelioma have been reported as candidates. In contrast, the expression in
renal carcinoma (ERC) gene has been discovered in the Eker rat model (Tsc2 gene
mutant), which is a homolog of the human mesothelin/megakaryocyte potentiating
factor gene, and a novel ELISA system (N-ERC/mesothelin) has been developed. It
has also been found that N-ERC/mesothelin is very stable and plentiful in the
blood. In the present paper the potential utility of molecular diagnostic markers
is reviewed, including ELISA systems for asbestos-related mesothelioma.
PMID- 17040287
TI - Immunohistochemical study of the relationship between Ki-67 labeling index of
proliferating cells of gynecomastia, histological phase and duration of disease.
AB - Gynecomastia is a benign proliferative lesion caused by various etiological
factors and may result from a relative imbalance between serum estrogen and
androgen levels. The histological alterations are similar, and gynecomastia can
progress from a florid type to a fibrous type. The Ki-67 labeling index (LI) of
gynecomastia specimen was investigated and higher Ki-67 LI was observed in florid
and intermediate than in fibrous gynecomastia (P = 0.017). A correlation was
found between the duration of disease and Ki-67 LI (P = 0.041): the shorter the
duration the higher the Ki-67 LI. Thus, Ki-67 LI seems a useful tool to examine
proliferation activity of gynecomastia and can assist in determination of
appropriate treatment of gynecomastia with hormonal therapy.
PMID- 17040288
TI - Immortalization of Epstein-Barr virus-negative human B lymphocytes with minimal
chromosomal instability.
AB - The genes required for immortalization of human B cells infected by Epstein-Barr
virus are multiple, and the precise mechanism of this process remains to be
elucidated. In the present study HPV16 E6 and E7 were retrovirally transduced
into human primary B cells stimulated by CD40-CD40L interaction, thereby
establishing an Epstein-Barr virus negative immortalized human B cell line, which
continued to proliferate for more than 2 years (100 population doublings). The
established cell line had a high telomerase activity from the beginning of the
culture period, and no shortening of the telomere length was observed. A
chromosomal analysis revealed that a large portion of the HPV16E6E7 transduced
cells had retained a normal karyotype. Similar to human epithelial cells, human B
lymphocytes seem to require two steps for immortalization, namely, the
inactivation of the p16/Rb pathway and the activation of telomerase, the latter
that can be induced by the CD40-CD40L interaction. Furthermore, using this
system, it is possible to analyze the role of individual genes in human B
lymphocyte immortalization without the influence of a pre-existing Epstein-Barr
virus genome.
PMID- 17040289
TI - Hepatosplenic gammadelta T-cell lymphoma following seven malaria infections.
AB - Hepatosplenic gammadelta T-cell lymphoma (HSTL) is a clinicopathological entity
associated with an immunocompromised status in approximately 25% of patients.
Herein is described a case of HSTL in a 53-year-old Brazilian man with seven
previous malaria infections, initially misdiagnosed as a hyperreactive
splenomegaly due to chronic malaria. A characteristic lymphoid infiltrate was
observed in spleen, liver and bone marrow sinusoids/sinuses. Neoplastic cells had
a CD45RO+, CD2+, CD7+, CD3+, CD5-, CD8+, CD56+, perforin+, FasL-negative, T-cell
receptor (TCR)alphabeta-negative, TCRgammadelta+ profile. Analyses of gamma and
delta TCR rearrangements confirmed diagnosis of gammadelta T-cell lymphoma by
detecting VgammaI/Vdelta1-Jdelta1 clonal rearrangements. Sensitive polymerase
chain reaction (PCR) for Plasmodium falciparum, Epstein-Barr virus and
herpesvirus-8 failed to demonstrate infection. The disease progressed to a fatal
outcome following cutaneous infiltration and leukemic proliferation. The authors
also comment on the association of lymphoma and infection, focusing on PCR
diagnosis of TCRgamma and delta clonal rearrangements and the presumed pathogenic
events leading to HSTL in the context of chronic malaria infection. Initial
lymphomagenic stages might not be direct consequences of antigenic stimulation of
Vdelta1 T-cells, but might depend on interactions between gammadelta T and B
cells during cooperative or regulatory responses to Plasmodium sp.
PMID- 17040290
TI - Sparganum mansoni parasitic infection in the lung showing a nodule.
AB - Reported herein is a 57-year-old man infected by Sparganum mansoni, a kind of
tapeworm, showing a solitary nodule of the middle lobe of the right lung. Because
a transbronchial biopsy could not diagnose the nodule, a right middle lobectomy
was performed on suspicion of malignant tumor. The lesion was diagnosed as
sparganosis by histological and immuno-serological examinations. Histological
examination revealed granulomatous inflammation with neutrophil and eosinophil
infiltration around the worm and interstitial pneumonia surrounding the nodule.
Moreover, vasculitis with foreign body giant cell was seen around the lesion. To
the authors' knowledge this is the second case of sparganosis limited in the
lung, and the current report presents the first detailed histological description
of a pulmonary sparganosis case.
PMID- 17040291
TI - Cockayne syndrome with recurrent acute tubulointerstitial nephritis.
AB - A 12-year-old girl, who had been diagnosed as having Cockayne syndrome (CS), was
admitted for emaciation and dehydration. On admission the patient had mild
chronic renal failure (glomerular filtration rate: GFR 50 mL/min) and
hyperuricemia. After rehydration, allopurinol was commenced for her
hyperuricemia. Then, her renal function rapidly deteriorated (GFR 20 mL/min) with
enhancement of proximal tubular dysfunction and hypertension. A renal biopsy
showed that the patient had acute tubulointerstitial nephritis (ATIN). Based on
this diagnosis, allopurinol was stopped and prednisolone was started (2 mg/kg per
day), following which the renal tubular function improved. However, the
proteinuria intensified to become nephrotic syndrome. After 1 month the patient
developed a gastric ulcer. Famotidine was commenced but GFR deteriorated and
renal proximal tubular dysfunction re-occurred. The renal pathology was evaluated
by referring to the previous reports of renal pathology in CS. It is suggested
that rapid deterioration of the renal function in CS patients might be the result
of ATIN. In addition, the present nephrotic syndrome seemed to be accompanied by
ATIN, as in other reports.
PMID- 17040292
TI - Pleomorphic lobular carcinoma in situ of the breast composed almost entirely of
signet ring cells.
AB - Some examples of lobular carcinoma in situ (LCIS) may be composed in part of
signet ring cells. Such proliferations have been considered examples of
pleomorphic LCIS based on pathological features of the more conventional
component. However, the occurrence of LCIS composed entirely of signet ring cells
is extraordinarily rare. This report describes an example of an in situ
proliferation that was composed almost entirely (>95%) of signet ring cells,
which was unassociated with an invasive carcinoma and which showed comedo-type
necrosis. There was only focal lobulocentric distention by lesional cells, as is
typical of classic LCIS. However, discrete, ductal-type cross-sectional profiles
showed a purely intraepithelial proliferation of remarkably discohesive signet
ring cells. The signet ring cells had intermediate-grade nuclear atypia, no
significant mitotic activity and were positive for mucicarmine and PAS stains
(the latter with and without diastase predigestion). The cells displayed marked
immunoreactivity for high-molecular-weight keratin (stained by 34beta E12
antibody), MUC1, gross cystic disease fluid protein-15, cytokeratin 7 and were
negative for cytokeratin 20, E-cadherin, progesterone receptor and HER2/neu. It
is concluded that this is an example of a purely signet ring variant of
pleomorphic LCIS.
PMID- 17040293
TI - Primary large cell neuroendocrine carcinoma of the urinary bladder.
AB - Primary large cell neuroendocrine carcinomas (LCNEC) of the urinary bladder are
rare. Reported herein is a case of a primary, pure LCNEC occurring in a man. The
patient was a 32-year-old man who presented with hematuria of 1 week's duration.
On cystoscopic examination, a solitary mass measuring 3 cm in diameter was
detected protruding from the anterosuperior wall of the urinary bladder. Two
months after the primary transurethral resection, significant regrowth of the
remnant mass was noted on CT, and the patient underwent a partial cystectomy. A
diagnosis of LCNEC was made based upon histological and immunohistochemical
findings. Tumor cells were positive for synaptophysin, chromogranin A, CD56,
epithelial membrane antigen, and cytokeratin. Histologically, the tumor
penetrated the deep muscle and perivesical fat. In spite of three cycles of
chemotherapy, the patient developed multiple metastases in the lung and liver 10
months postoperatively. LCNEC of the urinary bladder are uncommon entities, which
have a possible fatal outcome.
PMID- 17040294
TI - Unusual hemangioendothelioma of the liver with epithelioid morphology associated
with marked eosinophilia: autopsy case.
AB - Vascular neoplasms characterized by epithelioid endothelial cells consist of
several different entities from benignity to high-grade malignancy. Because of
histological overlap between them, there is substantial difficulty in classifying
them correctly. The present patient, a 33-year-old man, presented with
hepatomegaly, striking eosinophilia and elevated serum interleukin-5 level.
Biopsy and autopsy revealed an unusual epithelioid vascular tumor in the liver,
which is histologically distinct from epithelioid hemangioma, epithelioid
hemangioendothelioma, or epithelioid angiosarcoma. The tumor cells had
vasoformative and partly solid growth with no severe nuclear atypia and very low
mitotic activity, and the histological features were similar to those of the
entity recognized as hemangioendothelioma of bone. Organs other than the liver,
for example the testes and bone, were also involved. This tumor should be
considered in the differential diagnosis of severe eosinophilia.
PMID- 17040295
TI - SMARCB1/INI1 missense mutation in mucinous carcinoma with rhabdoid features.
AB - Malignant rhabdoid tumor (MRT) is a rare and aggressive tumor associated with
deletion or mutation of a tumor suppressor gene SMARCB1/INI1, a member of the
SWI/SNF chromatin-remodeling complex. Reported herein is a case of pancreatic
mucinous carcinoma accompanying rhabdoid features with immunohistochemical and
ultrastructural studies as well as analysis of the SMARCB1/INI1 gene. A 65-year
old woman presented with a 2 month history of abdominal and chest pain. A well
defined grayish tan fish-flesh mass (11 x 9 x 7 cm) with focal mucinous area was
present in the pancreatic tail. Microscopically, the tumor had a biphasic growth
pattern: a mucinous carcinoma component and a poorly differentiated carcinoma
component with rhabdoid features showing loosely cohesive cells with abundant
eosinophilic cytoplasm, displaced nuclei, and prominent nucleoli. The rhabdoid
component coexpressed vimentin and cytokeratin. Sequencing analysis of the DNA
extracted from the mucinous and rhabdoid components showed a missense mutation
CCC to ACC in codon 116 of the SMARCB1/INI1 gene. Being aware of rhabdoid
features would help diagnose this rare and aggressive malignant tumor and may
provide an opportunity for further evaluation of SMARCB1/INI1 gene alteration and
determination of its prognostic significance.
PMID- 17040296
TI - Non-cystic solid-pseudopapillary tumor of the pancreas showing nuclear
accumulation and activating gene mutation of beta-catenin.
AB - Solid-pseudopapillary tumor (SPT) is an unusual pancreatic neoplasm that is
characterized by a mixture of solid and cystic components and a fibrous capsule.
Recently, the tumorigenesis of SPT has been reported to be associated with gene
mutations of beta-catenin, which is a molecule participating in the Wnt signaling
pathway. Reported herein is the case of a 53-year-old woman with SPT. The tumor,
approximately 3 cm in diameter in the pancreas body, had a clear margin and
central calcification but had neither a cystic component nor fibrous capsule.
Several lines of pathological findings in the surgically resected specimen
indicated SPT: (i) pseudopapillary proliferation of eosinophilic polygonal cells
with oval nuclei; (ii) positive expression of several marker molecules indicating
differentiation into acinar and endocrine cells; and (iii) zymogen granule-like
structures in the cytoplasm on electron microscopy. Further, the tumor cells had
intense nuclear accumulation of beta-catenin and an activating mutation,
(34)Gly(GGA) to Arg(AGA), in exon 3 of the beta-catenin gene, as previously
reported in most SPT. These findings suggest that association of the beta-catenin
phenotype with development of the rare phenotype of SPT, a non-cystic and
unencapsulated tumor, is unlikely.
PMID- 17040297
TI - De novo cancers and post-transplant lymphoproliferative disorder in adult liver
transplantation.
AB - De novo cancer is one of the most serious complications after organ
transplantation. Chronic immunosuppression, viral agents, pretransplant chronic
alcohol-induced and other addictive behavior-induced injury are important
conditions associated with the development of de novo cancers in solid organ
transplants. The aim of the study was to evaluate types and clinical course of de
novo cancers in adult liver transplant recipients. Data regarding 502 adult
patients who underwent to 554 liver transplantations have been collected. Sex,
age at transplantation, immunosuppressive regimen, time from transplantation to
diagnosis of cancer, cancer type, surgical and non-surgical treatments and follow
up time have been analyzed as well as acute rejection episodes and viral status.
Thirty patients developed 31 de novo cancers. The predominant tumors were
carcinoma of the skin, lymphomas and Kaposi's sarcoma. Kaposi's sarcoma and lung
cancer were associated with greater mortality. In lymphomas and Kaposi's sarcoma,
a high rate of graft involvement was observed. In liver transplant recipients, de
novo cancers demand strategies focusing on prophylactic and careful long-term
screening protocols. Lymphomas and Kaposi's sarcoma should be ruled out in all
patients with clinical manifestations of chronic biliary obstruction.
PMID- 17040298
TI - Oxygen - elixir of life or Trojan horse? Part 1: oxygen and neonatal
resuscitation.
PMID- 17040299
TI - Ultrasonographic guidance in pediatric regional anesthesia. Part 2: techniques.
AB - The benefits of regional anesthesia are well documented. The downsides of such
techniques have been a significant failure rate and a potential for serious
complications. Nearly, all regional blocks were first described as essentially
'blind' techniques. The development of high-resolution portable ultrasound (US)
has made the use of US for regional anesthesia possible. Improved understanding
of sonographic anatomy should lessen both the failure rate and the possibility of
incurring serious complications. Natural caution has dictated that only a
selection of blocks used in adults has been commonly used in pediatric practice,
but with the aid of US, the repertoire of blocks for infants and children may be
widened. The second part of this review will concentrate on the practice of both
peripheral and central blocks.
PMID- 17040300
TI - Outpatient arthroscopic knee surgery under combined local and intravenous
propofol anesthesia in children and adolescents.
AB - BACKGROUND: This prospective observational study included a case series of
children and adolescents receiving light intravenous propofol anesthesia combined
with local anesthesia (LA) for arthroscopic knee procedures. The aim was to
examine the merits of anesthesia, to discuss the indications for the procedure
and to analyze recovery/discharge times from the postanesthesia care unit (PACU).
METHODS: A cohort of 147 children and adolescents (ASA 1 and 2) aged 12-18 years
admitted for outpatient arthroscopic knee procedures between January 2004 and May
2005 were studied. After IV access in the operating theater, the patients
received propofol (10 mg.ml(-1)). Arthroscopy was performed approximately 15 min
after injecting local anesthetic (15 ml 2% lidocaine with epinephrine 1:200,000)
partly at the site of insertion of the arthroscope and other instruments (5 ml),
and the rest intra-articular. The following parameters were assessed: airway
patency, propofol requirement, vital signs, procedure time, surgical operating
conditions, patient satisfaction score, time to discharge, postoperative
analgesia and adverse events. RESULTS: Of 147 patients, 133 patients (90.5%)
underwent arthroscopic knee surgery, whereas knee arthroscopy alone was performed
in 14 patients (9.5%) without indication for operative treatment. The arthroscopy
was well tolerated in 96.6% patients (no pain, movement or discomfort during the
procedure) and only five patients required conversion to general anesthesia. Pain
experienced during the injection of lidocaine was more severe than pain
experienced during the surgical procedure itself (P < 0.001). The surgical
evaluation of operative conditions (visualization and access to intra-articular
structures) was generally satisfactory and completely acceptable. Almost 94%
(138/147) of patients said they would have the same procedure again under the
same type of anesthesia. The mean propfol induction dose was 1.4 mg.kg(-1)
(range: 0.9-3.8) and mean propofol infusion rate 167 microg.kg(-1).min(-1)
(range: 130-250). Movement was more likely at lower infusion rates (mean: 151
microg.kg(-1).min(-1)). The maximal decrease in respiratory rate was 5.9 +/- 5.1
br.min(-1) (27.2 +/- 21%) and no patient became hypoxic. Patients recovered to
preoperative values at 9.8 +/- 7.5 min following infusion discontinuation. There
were no respiratory or cardiovascular complications. The mean stay in PACU was 47
min (range: 32-150). As many as 71% (105/147) of patients required no analgesics
during the first two postoperative hours. CONCLUSIONS: The combination of light
intravenous propofol anesthesia combined with local anesthesia for arthroscopic
knee procedures provided effective sedation, good preservation of upper airway
patency, rapid recovery and pain relief without major side effects and offers a
good alternative to the methods already available. The majority of patients did
not require postoperative analgesia.
PMID- 17040301
TI - Esophageal saturation during antegrade cerebral perfusion: a preliminary report
using visible light spectroscopy.
AB - BACKGROUND: Visible light spectroscopy (VLS) is newer technology that measures
real-time tissue oxygenation. It has been validated in detecting mucosal ischemia
in adults. During complex neonatal heart surgery, antegrade cerebral perfusion
(ACP) maintains cerebral saturation. Whether ACP maintains peripheral tissue
perfusion in humans is not known. METHODS: Five patients undergoing neonatal open
heart surgery with hypothermic cardiopulmonary bypass (CPB) were studied using a
VLS esophageal probe in addition to bilateral near infrared cerebral oximetry.
Three of five patients required ACP for arch repair, while two patients did not.
VLS and cerebral saturation data were collected and analyzed in 5 min intervals
prior to CPB, during CPB, and during ACP. RESULTS: In the two patients undergoing
heart surgery with routine hypothermic CPB, both cerebral and esophageal
saturations were maintained. However in all three neonates requiring ACP,
although cerebral saturations did not decrease, esophageal saturation fell below
the ischemic threshold (35%). Following establishment of normal CPB, esophageal
saturation returned to baseline. CONCLUSIONS: Antegrade cerebral perfusion
maintains cerebral oxygen delivery, however, it does not adequately perfuse the
esophagus in neonates. This could have clinical implications.
PMID- 17040302
TI - Emergence agitation in preschool children: double-blind, randomized, controlled
trial comparing sevoflurane and isoflurane anesthesia.
AB - BACKGROUND: This randomized, double-blind controlled trial was conducted to
determine whether the association of sevoflurane for induction and isoflurane for
anesthesia maintenance resulted in a lower incidence of postoperative agitation
compared with sevoflurane as single agent. METHODS: After Institute Ethics
Committee's approval and parental written informed consent, 128 unpremedicated
children (1-6 years), ASA I-II, scheduled for elective subumbilical surgery were
enrolled. After induction with 8% sevoflurane, patients were randomly allocated
to receive sevoflurane or isoflurane 1-1.5 MAC as maintenance agent. The primary
endpoint of the study was the incidence of postoperative agitation defined as a
screaming and crying child and/or a child that required physical restraint during
emergence. RESULTS: Eighteen children were excluded because they received
sedatives, analgesia or anesthesia or because of ineffective regional analgesia
before randomization. Fifty-four patients receiving sevoflurane and 56 receiving
isoflurane completed the study. Twenty-eight children (95% CI 38-66%) in the
sevoflurane group presented with postoperative agitation compared with 18 (95% CI
20-46%) patients receiving isoflurane (P = 0.028). Fifteen minutes after
awakening, 11/54 children receiving sevoflurane were agitated compared with 4/56
receiving isoflurane (P = 0.03). Thereafter, there was a gradual reduction in the
incidence of postoperative agitation over time. CONCLUSIONS: The association of
sevoflurane for induction and isoflurane for maintenance produced significant
less postoperative agitation in preschool children receiving regional anesthesia
during subumbilical surgery compared with sevoflurane for induction and
maintenance.
PMID- 17040303
TI - Safe removal of LMA in children - at what BIS?
AB - BACKGROUND: Removal of an LMA without producing untoward complications has
remained a matter of concern to all anesthesiologists; more so in pediatric
practice where the margin of safety is narrow. Most work on LMA in adults
supports its removal following return of airway reflexes. The situation regarding
its removal in children is, however, less clear. METHODS: We conducted a
randomized, prospective study to compare incidence of airway complications after
removal of the LMA at deep or awake planes in 120 children, ASA I or II, aged 1-8
years and to objectively determine the most appropriate Bispectral index (BIS) to
allow safe removal of an LMA in children. They were studied in two groups of 60
and depth of anesthesia (whether awake-Gp A or deep-Gp D) for LMA removal was
decided by random distribution from sealed envelopes. BIS was recorded
continuously for all the patients until 2 min after removal of LMA. RESULTS: Mean
SpO2 after removal of LMA was 93% Gp A and 98% in Gp D. The mean duration of
surgery in Gp A was 53.9 +/- 10 and in Gp D 46.7 +/- 4 min. PESev at removal in
Gp A was 0.20 +/- 0.16 and in Gp D was 0.59 +/- 0.1. BIS median in Gp A was 79
with a maximum of 86 and minimum of 66. In Gp D BIS, median was 60 with maximum
of 76 and minimum of 58. The number of patients with airway complications in
awake removal group was 21 (35%) and in deep removal group was 4 (6.6%).
CONCLUSIONS: Bispectral index scoring should prove a useful adjunct to the
present monitoring and can be used to achieve smoother emergence conditions. We
suggest that LMA removal should be attempted in children when a BIS value of
approximately 60 is reached.
PMID- 17040304
TI - Pain management in fulminating ulcerative colitis.
AB - BACKGROUND: Toxic megacolon is a life-threatening complication of ulcerative
colitis (UC) characterized by systemic toxicity, loss of blood per rectum and
severe pain. Pain management is challenging in these patients because
nonsteroidal anti-inflammatory drugs may exacerbate bleeding and opioids are
contraindicated because they adversely affect bowel peristalsis causing an
increased risk of colonic perforation. METHODS: We describe three episodes of
fulminating UC in two children in whom ketamine analgesia was used. Our protocol
for a low-dose continuous ketamine infusion with either nurse-controlled
analgesia (NCA) or patient-controlled analgesia (PCA) bolus administration is
presented and a review of the literature regarding the use of ketamine analgesia
in children is discussed. RESULTS: Low-dose ketamine N/PCA with a continuous
background infusion provided satisfactory analgesia and none of our children
reported adverse effects. CONCLUSIONS: We have demonstrated the safe and
effective use of ketamine analgesia in children with toxic megacolon, a condition
in which the child is in severe pain and morphine is contraindicated.
PMID- 17040305
TI - A factorial study of ondansetron, metoclopramide, and dexamethasone for emesis
prophylaxis after adenotonsillectomy in children.
AB - BACKGROUND: We conducted a factorial study of emesis prophylaxis with ondansetron
(OND), metoclopramide (MET), and dexamethasone (DEX). METHODS: After informed
parental consent, 240 children having adenotonsillectomy were randomized to one
of 15 combinations of OND (0-60 microg.kg(-1)), MET (0-400 microg.kg(-1)), and/or
DEX (0-500 microg.kg(-1)). Using multivariable logistic regression, models were
generated for the probability of emesis before discharge, after discharge and
overall for 24 h. RESULTS: Odds of emesis increased by a factor of three to four
for children older than 7 years. Before discharge, odds of emesis decreased by
factors of 0.29 for each 15 microg.kg(-1) of OND and 0.37 for each 100 microg.kg(
1) of MET. After discharge, odds of emesis decreased by a factor of 0.67 for each
125 microg.kg(-1) of DEX and increased by a factor of 3.5 for emesis before
discharge. Over 24 h, odds of emesis decreased with OND, MET, and DEX (ORs as
above). A negative interaction between OND and MET was seen before discharge and
over 24 h, reducing the efficacy of their combination. CONCLUSIONS: We present
novel study design and methods of analysis which are uniquely suited to studies
of multiple interventions. Factorial design was a powerful tool, allowing
simultaneous determination of dose-response relationships for three drugs and
identifying a previously unreported negative interaction between OND and MET.
PMID- 17040306
TI - Intraoperative and postoperative risk factors for prolonged mechanical
ventilation after pediatric cardiac surgery.
AB - BACKGROUND: Early extubation after cardiac surgery in children is feasible;
however, predictors of prolonged mechanical ventilation (MV) should be recognized
as soon as possible. METHODS: At a tertiary pediatric cardiac center, prospective
case series analyses were carried out with a total of 411 patients within 1 year
of cardiac surgery. Perioperative factors were evaluated for strength of
association with duration of MV > 61 h (medium, MMV) and > 7 days (long, LMV).
Two multiple regression models were performed for both cut-off points: one model
considered factors identified until 24 h postoperation, the other was performed
with all parameters. RESULTS: One hundred and three patients (25%) were still
intubated after 61 h; 38 patients required LMV and they occupied 33% of total
intensive care unit (ICU) bed days. If factors occurring until 24 h after surgery
were analyzed, duration of cardiopulmonary bypass (CPB), intraoperative
transfusion, post-CPB arterial oxygen tension (PaO2/FiO2), and fluid intake on
the first day were found to be associated with MMV. Urea nitrogen value, nitric
oxide treatment, delayed sternal closure, and tracheobronchomalacia, measured at
the same point of time, were independent predictors of LMV. Of all the studied
clinical predictors, MMV was associated with pulmonary hypertensive events,
delayed sternal closure, peritoneal dialysis, nonvascular pulmonary problems, low
output syndrome and fluid intake, while urea nitrogen (24 h), postsurgical
neurological events, nitric oxide, tracheobronchomalacia, pulmonary hypertensive
events and cardiac reoperations were identified as determinants of LMV.
CONCLUSIONS: Causes of MV after surgery are heterogeneous, vary with time, and
have variable impact on the duration of MV.
PMID- 17040307
TI - Continuous venovenous hemodiafiltration to treat controlled-release carbamazepine
overdose in a pediatric patient.
AB - Carbamazepine (CBZ) intoxication is an important issue in acute poisoning
practice. Highly protein-bound, CBZ is not removed efficiently through
conventional hemodialysis. We describe the use of continuous venovenous
hemodiafiltration (CVVHDF) in a 2-year-old boy who developed general tonic clonic
seizure and respiratory depression due to controlled-release formula of CBZ
overdose (peak drug level of > 20 microg.ml(-1), therapeutic range: 5-10
microg.ml(-1)). Serum CBZ concentrations fell to 0.25 microg.ml(-1) at the end of
hemodiafiltration. The patient recovered rapidly and was discharged from hospital
4 days from the time of ingestion with no complications or neurologic impairment.
PMID- 17040308
TI - Cardiac arrest at induction of anesthesia in a child with undiagnosed right
ventricular dependent coronary circulation: a case report.
AB - Pediatric perioperative cardiac arrest occurs in 1.4 per 10,000 anesthetics, with
an overall mortality rate of 26%. The etiology of the arrest is identifiable in
the majority of these patients. We report the case of a child with a complex
congenital heart defect, who sustained a cardiac arrest at induction of
anesthesia, secondary to right-ventricular dependent coronary circulation. We
discuss the incidence, risks, anesthetic management and outcomes of pediatric
cardiac arrest in the perioperative period especially in patients with complex
congenital heart disease.
PMID- 17040309
TI - Anesthesia management with short acting agents for bilateral pheochromocytoma
removal in a 12-year-old boy.
AB - A 12-year-old boy with bilateral adrenal pheochromocytoma pretreated with
furosemide, nifedipine, prazosin, and propranolol underwent surgical removal of
the tumors. General anesthesia with desflurane, remifentanil infusion and
thoracic epidural analgesia was performed. To control the blood pressure (BP),
remifentanil up to 1 microg.kg(-1).min(-1) infusion rate, sodium nitroprusside,
and esmolol infusions were administered successfully. Following the ligation of
the adrenal veins, hemodynamic parameters were stable and neither inotropic
support nor corticosteroid replacement was required. We concluded that
remifentanil-based anesthesia combined with low-dose desflurane and thoracic
epidural analgesia may reduce the need for vasoactive drugs in the anesthesia
management of pheochromocytoma. This combination may not prevent the hemodynamic
fluctuations during tumor manipulation, but appears to facilitate a rapid and
stable postoperative recovery.
PMID- 17040310
TI - Anesthesia management for the child with Sanjad-Sakati syndrome.
AB - Sanjad-Sakati syndrome (SSS) is a rare genetic disorder characterized by
congenital hypoparathyroidism, hypocalcemia and hyperphosphatemia, seizures,
severe intrauterine and postnatal growth failure, dwarfism, mental retardation,
dysmorphic features including retromicrognathia and abnormal dentition and
increased susceptibility to infection. It is mainly confined to children in the
Middle-East countries. We report the anesthesia management of a 12-year-old boy
with SSS for dental treatment, and discuss the anesthesia implications of this
disorder.
PMID- 17040311
TI - Therapeutic airway obstruction.
PMID- 17040312
TI - Intraoperative cardiac arrest because of oculocardiac reflex and subsequent
pulmonary edema in a patient with extraocular cysticercosis.
PMID- 17040313
TI - Anesthetic management of a patient with Moyamoya disease undergoing open heart
surgery.
PMID- 17040314
TI - To make epidural catheterization less difficult in infants.
PMID- 17040315
TI - Caudal anesthesia in children with shunt devices.
PMID- 17040316
TI - Torsades de pointes with sevoflurane.
PMID- 17040318
TI - Inadvertent bolus administration of high-dose remifentanil during anesthesia in a
6-year-old girl.
PMID- 17040319
TI - Predation on mutualists can reduce the strength of trophic cascades.
AB - Ecologists have put forth several mechanisms to predict the strength of predator
effects on producers (a trophic cascade). We suggest a novel mechanism--in
systems in which mutualists of plants are present and important, predators can
have indirect negative effects on producers through their consumption of
mutualists. The strength of predator effects on producers will depend on their
relative consumption of mutualists and antagonists, and on the relative
importance of each to producer population dynamics. In a meta-analysis of
experiments that examine the effects of predator reduction on the pollination and
reproductive success of plants, we found that the indirect negative effects of
predators on plants are quite strong. Most predator removal experiments measure
the strength of predator effects on producers through the antagonist pathway; we
suggest that a more complete understanding of the role of predators will be
achieved by simultaneously considering the effects of predators on plant
mutualists.
PMID- 17040320
TI - The silver spoon effect and habitat selection by natal dispersers.
AB - The silver spoon effect in the context of habitat selection occurs when
dispersers in good condition are more likely to settle in high-quality habitats
than dispersers in poor condition. Positive relationships between disperser
condition and the quality of post-dispersal habitats are predicted by at least
two non-exclusive ultimate hypotheses. The competition hypothesis assumes that a
disperser's condition affects its chances of competing for space or joining an
established group after arriving at a high-quality habitat, while the search
hypothesis assumes that a disperser's condition affects its selectivity, and
hence its chances of accepting a lower-quality habitat when it is searching for a
new habitat. Thus far, silver spoon effects in the context of habitat selection
have been reported in only a handful of species (several birds and marine
invertebrates), but this study suggests that they may be relatively common in
particular species and situations.
PMID- 17040321
TI - Stoichiometry of consumer-driven nutrient recycling across nutrient regimes in
streams.
AB - Stoichiometric constraints within ecological interactions and their ecosystem
consequences may depend on characteristics of the abiotic environment such as
background nutrient levels. We assessed whether consumer identity, via differing
body stoichiometry, could regulate periphyton stoichiometry across nutrient
regimes in open systems. In 60 flow-through artificial streams, we factorially
crossed dissolved inorganic nitrogen levels (elevated = 294 micog L(-1), ambient
= 26 microg L(-1)) with dissolved inorganic phosphorus levels (DIP: elevated = 15
microg L(-1), ambient = 3 microg L(-1)) and consumer type [crayfish (body N : P =
18), snails (body N : P = 28) or a control]. At ambient DIP, periphyton in the
crayfish treatment had a lower %P and a lower C : P than periphyton in the snail
treatment suggesting that consumer identity, probably mediated by differing P
excretion, regulated periphyton P content. At high DIP, consumer identity no
longer affected periphyton elemental composition. Therefore, the stoichiometry of
consumer-driven nutrient recycling and consumer identity may be less important to
ecosystem functioning in environments with elevated nutrient levels.
PMID- 17040322
TI - Weed evolution after crop gene introgression: greater survival and fecundity of
hybrids in a new environment.
AB - Crop-wild hybridization may produce offspring with lower fitness than their wild
parents due to deleterious crop traits and outbreeding depression. Over time,
however, selection for improved fitness could lead to greater invasiveness of
hybrid taxa. To examine evolutionary change in crop-wild hybrids, we established
four wild (Raphanus raphanistrum) and four hybrid radish populations (R.
raphanistrum x Raphanus sativus) in Michigan (MI), USA. Hybrid and wild
populations had similar growth rates over four generations, and pollen fertility
of hybrids improved. We then measured hybrid and wild fitness components in two
common garden sites within the geographical range of wild radish [MI and
California (CA)]. Advanced generation hybrids had slightly lower lifetime
fecundity than wild plants in MI but exhibited c. 270% greater lifetime fecundity
and c. 22% greater survival than wild plants in CA. Our results support the
hypothesis that crop-wild hybridization may create genotypes with the potential
to displace parental taxa in new environments.
PMID- 17040323
TI - Invariant scaling of phytoplankton abundance and cell size in contrasting marine
environments.
AB - Scaling relationships such as the variation of population abundance with body
size provide links between individual organisms and ecosystem functioning.
Previous work, in marine pelagic ecosystems, has focused on the relationship
between total phytoplankton abundance and the assemblage mean cell size. However,
the relationship between specific population abundance and cell size in marine
phytoplankton has received little attention. Here, we show that cell size
accounts for a significant amount of variability in the population abundance of
phytoplankton species across a cell volume range spanning seven orders of
magnitude. The interspecific scaling of population abundance and cell size takes
a power exponent near -3/4. Unexpectedly, despite the constraints imposed on
large phytoplankton by limited resource acquisition, the size scaling exponent
does not differ between contrasting marine environments such as coastal and
subtropical regions. These findings highlight the adaptive abilities of
individual species to cope with different environmental conditions and suggest
that a general rule such as the 'energetic equivalence' constrains the abundance
of phytoplankton populations in marine pelagic ecosystems.
PMID- 17040324
TI - Structure of Caribbean coral reef communities across a large gradient of fish
biomass.
AB - The collapse of Caribbean coral reefs has been attributed in part to historic
overfishing, but whether fish assemblages can recover and how such recovery might
affect the benthic reef community has not been tested across appropriate scales.
We surveyed the biomass of reef communities across a range in fish abundance from
14 to 593 g m(-2), a gradient exceeding that of any previously reported for coral
reefs. Increased fish biomass was correlated with an increased proportion of apex
predators, which were abundant only inside large marine reserves. Increased
herbivorous fish biomass was correlated with a decrease in fleshy algal biomass
but corals have not yet recovered.
PMID- 17040325
TI - Allometric scaling enhances stability in complex food webs.
AB - Classic local stability theory predicts that complex ecological networks are
unstable and are unlikely to persist despite empiricists' abundant documentation
of such complexity in nature. This contradiction has puzzled biologists for
decades. While some have explored how stability may be achieved in small modules
of a few interacting species, rigorous demonstrations of how large complex and
ecologically realistic networks dynamically persist remain scarce and
inadequately understood. Here, we help fill this void by combining structural
models of complex food webs with nonlinear bioenergetic models of population
dynamics parameterized by biological rates that are allometrically scaled to
populations' average body masses. Increasing predator-prey body mass ratios
increase population persistence up to a saturation level that is reached by
invertebrate and ectotherm vertebrate predators when being 10 or 100 times larger
than their prey respectively. These values are corroborated by empirical predator
prey body mass ratios from a global data base. Moreover, negative effects of
diversity (i.e. species richness) on stability (i.e. population persistence)
become neutral or positive relationships at these empirical ratios. These results
demonstrate that the predator-prey body mass ratios found in nature may be key to
enabling persistence of populations in complex food webs and stabilizing the
diversity of natural ecosystems.
PMID- 17040326
TI - Spatial segregation of specialists and generalists in bird communities.
AB - Each species generally has a close relationship with one or more habitats and can
therefore be classified as either specialist or generalist. We studied whether
specialist and generalist species are spatially distributed independently of each
other. Repeating the analysis for 100 of the most frequent terrestrial bird
species recorded over the 10 000 sampled sites of the French Breeding Bird
survey, we found that specialists were more abundant if the rest of the community
was specialized, and that the inverse was also true. This pattern was far subtler
than just a simple dichotomy: most species actually presented a maximum abundance
at a value of community specialization similar to their own level of
specialization. Bird communities appear very well defined along a specialist
generalist gradient. We believe this pattern becomes more apparent with habitat
degradation. The consequences on both ecological services and community
resilience may well be considerable.
PMID- 17040327
TI - Habitat effects on the relative importance of trait- and density-mediated
indirect interactions.
AB - Classical views of trophic cascades emphasize the primacy of consumptive predator
effects on prey populations to the transmission of indirect effects [density
mediated indirect interactions (DMIIs)]. However, trophic cascades can also
emerge without changes in the density of interacting species because of non
consumptive predator effects on prey traits such as foraging behaviour [trait
mediated indirect interactions (TMIIs)]. Although ecologists appreciate this
point, measurements of the relative importance of each indirect predator effect
are rare. Experiments with a three-level, rocky shore food chain containing an
invasive predatory crab (Carcinus maenas), an intermediate consumer (the snail,
Nucella lapillus) and a basal resource (the barnacle, Semibalanus balanoides)
revealed that the strength of TMIIs is comparable with, or exceeds, that of
DMIIs. Moreover, the sign and strength of each indirect predator effect depends
on whether it is measured in risky or refuge habitats. Because habitat shifts are
often responsible for the emergence of TMIIs, attention to the sign and strength
of these interactions in both habitats will improve our understanding of the link
between individual behaviour and community dynamics.
PMID- 17040328
TI - How parasites affect interactions between competitors and predators.
AB - We present a synthesis of empirical and theoretical work investigating how
parasites influence competitive and predatory interactions between other species.
We examine the direct and indirect effects of parasitism and discuss examples of
density and parasite-induced trait-mediated effects. Recent work reveals
previously unrecognized complexity in parasite-mediated interactions. In addition
to parasite-modified and apparent competition leading to species exclusion or
enabling coexistence, parasites and predators interact in different ways to
regulate or destablize the population dynamics of their joint prey. An emerging
area is the impact of parasites on intraguild predation (IGP). Parasites can
increase vulnerability of infected individuals to cannibalism or predation
resulting in reversed species dominance in IGP hierarchies. We discuss the
potential significance of parasites for community structure and biodiversity, in
particular their role in promoting species exclusion or coexistence and the
impact of emerging diseases. Ongoing invasions provide examples where parasites
mediate native/invader interactions and play a key role in determining the
outcome of invasions. We highlight the need for more quantitative data to assess
the impact of parasites on communities, and the combination of theoretical and
empirical studies to examine how the effects of parasitism scale up to community
level processes.
PMID- 17040330
TI - Psychiatric comorbidity of migraine.
AB - Migraine affects nearly 12% of the adult population in the United States and
causes significant lost productivity and decrements in health-related quality of
life. The burden of migraine and the challenge in managing it are increased by
the comorbid psychiatric conditions that occur in association with it. Studies in
both clinical and community-based settings have demonstrated an association
between migraine and a number of specific psychiatric disorders. This review will
focus on the relationships between migraine and depression, generalized anxiety
disorder, panic disorder, and bipolar disorder. In large scale population-based
studies, persons with migraine are from 2.2 to 4.0 times more likely to have
depression. In longitudinal studies, the evidence supports a bidirectional
relationship between migraine and depression, with each disorder increasing the
risk of the other disorder. Migraine is also comorbid with generalized anxiety
disorder (Odds Ratio [OR] 3.5 to 5.3), panic disorder (OR 3.7), and bipolar
disorder (OR 2.9 to 7.3). A diagnosis of migraine should lead to a heightened
level of diagnostic suspicion for these comorbid psychiatric disorders.
Similarly, a diagnosis of one of these psychiatric disorders should increase
vigilance for migraine. Treatment plans for migraine should be mindful of the
comorbid conditions.
PMID- 17040331
TI - Modifiable risk factors for migraine progression.
AB - Migraine is a chronic-recurrent disorder that progresses in some individuals.
Transformed migraine is the result of this progression. Since migraine does not
progress in most patients, identifying the risk factors for progression has
emerged as a very important public health priority. If risk factors can be
identified, that might provide a foundation for more aggressive preventive
intervention. Risk factors for progression may be divided into non-remediable
(gender, age, race) and remediable categories. In this paper, we focus on several
already identified remediable risk factors, including frequency of migraine
attacks, obesity, acute medication overuse, caffeine overuse, stressful life
events, depression, and sleep disorders. We present the evidence for each risk
factor and discuss possible interventions to address them.
PMID- 17040332
TI - Headache and sleep disorders: review and clinical implications for headache
management.
AB - Review of epidemiological and clinical studies suggests that sleep disorders are
disproportionately observed in specific headache diagnoses (eg, migraine, tension
type, cluster) and other nonspecific headache patterns (ie, chronic daily
headache, "awakening" or morning headache). Interestingly, the sleep disorders
associated with headache are of varied types, including obstructive sleep apnea
(OSA), periodic limb movement disorder, circadian rhythm disorder, insomnia, and
hypersomnia. Headache, particularly morning headache and chronic headache, may be
consequent to, or aggravated by, a sleep disorder, and management of the sleep
disorder may improve or resolve the headache. Sleep-disordered breathing is the
best example of this relationship. Insomnia is the sleep disorder most often
cited by clinical headache populations. Depression and anxiety are comorbid with
both headache and sleep disorders (especially insomnia) and consideration of the
full headache-sleep-affective symptom constellation may yield opportunities to
maximize treatment. This paper reviews the comorbidity of headache and sleep
disorders (including coexisting psychiatric symptoms where available). Clinical
implications for headache evaluation are presented. Sleep screening strategies
conducive to headache practice are described. Consideration of the spectrum of
sleep-disordered breathing is encouraged in the headache population, including
awareness of potential upper airway resistance syndrome in headache patients
lacking traditional risk factors for OSA. Pharmacologic and behavioral sleep
regulation strategies are offered that are also compatible with treatment of
primary headache.
PMID- 17040333
TI - The neuropsychology of recurrent headache.
AB - Headache is recognized as one of the most prevalent neurological disorders, and
is the most frequently reported symptom following injury to the head, brain, or
neck. Although studies of central nervous system abnormalities in headache
sufferers have emerged in recent years, less is known about the associated
functional impairments. The research literature addressing neuropsychological
consequences of headache has been far from conclusive. Migraine has been most
extensively studied, with some consistent evidence of subtle but potentially
significant changes in cognition occurring during and between migraine episodes.
It also appears likely that migraine patients with aura experience more
neuropsychological deficits than those without aura. While the literature devoted
to understanding the neurocognitive profile of migraine sufferers is growing,
much less research has addressed the neuropsychology of tension-type headache and
posttraumatic headache (PTHA). There is some suggestion of poorer
neuropsychological function in tension-type headache than controls, but the
evidence is inconclusive. The PTHA population is highly varied in degree and
location of trauma, preexisting headache condition, and other injury-related
variables, allowing little generalization across studies. This paper summarizes
research regarding the cognitive symptoms associated with migraine, tension-type
headache, and PTHA, provides an overview of the cognitive side effects of
headache medications, and addresses clinical implications and priorities for
future research.
PMID- 17040334
TI - Understanding psychological stress, its biological processes, and impact on
primary headache.
AB - Psychological stress is generally acknowledged to be a central contributor to
primary headache. Stress results from any challenge or threat, either real or
perceived, to normal functioning. The stress response is the body's activation of
physiological systems, namely the hypothalamic-pituitary-adrenal axis, to protect
and restore functioning. Chronic activation of the stress response can lead to
wear and tear that eventually can predispose an individual to disease. There are
multiple ways that stress and headache are closely related. Stress can (a) be a
predisposing factor that contributes to headache disorder onset, (b) accelerate
the progression of the headache disorder into a chronic condition, and (c)
precipitate and exacerbate individual headache episodes. How stress impacts
headache is not often understood. However, stress is assumed to affect primary
headache by directly impacting pain production and modulation processes at both
the peripheral and central levels. Stress can also independently worsen headache
related disability and quality of life. Finally, the headache experience itself
can serve as a stressor that compromises an individual's health and well-being.
With the prominent role that stress plays in headache, there are implications for
the evaluation of stress and the use of stress reduction strategies at the
various stages of headache disorder onset and progression. Future directions can
help to develop a better empirical understanding of the pattern of the stress and
headache connections and the mechanisms that explain the connections. Further
research can also examine the interactive effects of stress and other factors
that impact headache disorder onset, course, and adjustment.
PMID- 17040335
TI - Behavioral facilitation of medical treatment for headache--part I: Review of
headache treatment compliance.
AB - Noncompliance or nonadherence with medical regimens represents a major challenge
to the practice of medicine including the treatment of headache. Indeed,
medication use patterns are particularly relevant to headache because of the
potential for headache therapies to induce medication-overuse headache. Previous
research has demonstrated that adherence to long-term medication therapy for
various chronic illnesses averages only about 50%. The rate of adherence among
headache patients has been found to be similarly poor. Misuse or overuse of
symptomatic medication has been demonstrated to contribute to treatment failure,
and one-fourth to one-half of patients are noncompliant with prophylactic
headache medications and at least 40% nonadherent with appointment-keeping.
Adherence declines with more frequent and complex dosing regimens, side effects,
and costs, and is subject to a wide range of psychosocial influences. Subjective
reports of adherence are likely not only to overestimate but also to be
discordant with more objective measurements. As the first of 2 articles, this
paper describes the problem of noncompliance in medical practice and reviews
literature addressing compliance specific to headache management. A companion
paper (Behavioral Facilitation of Medical Treatment for Headache--Part II:
Theoretical Models and Behavioral Strategies for Improving Adherence) summarizes
social learning models proposed to characterize the multiple determinants of
adherence and guide behavioral adherence-enhancing interventions, and then
presents cognitive and behavioral strategies that may facilitate treatment
adherence with headache patients.
PMID- 17040336
TI - Behavioral facilitation of medical treatment for headache--part II: Theoretical
models and behavioral strategies for improving adherence.
AB - This is the second of 2 articles addressing the problem of noncompliance in
medical practice and, more specifically, compliance with headache treatment. The
companion paper describes the problem of noncompliance in medical practice and
reviews literature addressing compliance in headache care (Behavioral
Facilitation of Medical Treatment for Headache--Part I: Review of Headache
Treatment Compliance). The present paper first summarizes relevant health
behavior theory to help account for the myriad biopsychosocial determinants of
adherence, as well as patient's shifting responsiveness or "readiness for change"
over time. Appreciation of health behavior models may assist in optimally
tailoring interventions to patient needs through instructional, motivational, and
behavioral treatment strategies. A wide range of specific cognitive and
behavioral compliance-enhancing interventions are described, which may facilitate
treatment adherence among headache patients. Strategies address patient
education, patient/provider interaction, dosing regimens, psychiatric
comorbidities, self-efficacy enhancement, and other behavioral interventions.
PMID- 17040337
TI - Headache and psychological functioning in children and adolescents.
AB - Headache can affect all aspects of a child's functioning, leading to negative
affective states (eg, anxiety, depression, anger) and increased psychosocial
problems (for instance, school absences, problematic social interactions). For
children and adolescents who experience frequent headache problems, comorbid
psychological issues are a well-recognized, but poorly understood, clinical
phenomenon. The confusion surrounding the relationship between pediatric headache
and psychopathology exists for several reasons. First, in some cases, headache
has been inappropriately attributed to psychological or personality features
based on anecdotal observations or interpretations that go beyond the available
data. Additionally, measures of psychopathology have not always adhered to the
American Psychiatric Association's diagnostic criteria, thus reducing the
reliability of diagnostic judgments. Furthermore, the diagnosis of headache has
not always followed standard criteria, and has been complicated by the emergence
of new terms and evolving measures. Finally, methodological shortcomings, such as
incomplete descriptions of the procedures and criteria used for the study,
inadequate descriptions of headache severity, lack of a control group for
comparison with individuals without headaches, reliance primarily on cross
sectional research designs that are often discussed with inferences to causal
hypotheses, and the use of unstandardized assessment measures, have significantly
limited the validity of research findings. The goal of the current review is to
examine the extant literature to provide the most up-to-date picture on what the
research has made available about the magnitude, specificity, and causes of
psychopathology in children and adolescents with headache, in an effort to
further elucidate their relationship and prompt a more methodologically rigorous
study of these issues.
PMID- 17040338
TI - The comorbidity of headache with other pain syndromes.
AB - In this article, we consider the possible reasons and supporting evidence for the
comorbidity of chronic pain conditions. To simplify the discussion, we primarily
focus on the epidemiology of headache with other pain conditions, dividing
studies into those based on children or adolescents and those based on adults. We
consider exogenous and endogenous factors, and methodological challenges, in
understanding whether and how 2 pain conditions may be related.
PMID- 17040339
TI - Topiramate prophylaxis and response to triptan treatment for acute migraine.
AB - OBJECTIVE: To evaluate the effect of topiramate migraine prophylaxis on subject
responsiveness to triptans used for acute symptomatic migraine treatment.
BACKGROUND: Clinical experience suggests that prophylactic migraine treatment may
enhance the efficacy of symptomatic medications used to treat acute migraine
attacks. METHODS: This open-label, single-arm multicenter study consisted of a 6
week baseline period followed by a 16-week topiramate treatment period. Subjects
meeting International Headache Society (IHS) criteria for migraine with and
without aura signed consent and entered the baseline period. Those with 3 to 12
migraine periods per month during baseline received topiramate prophylactic
treatment. Only patients who completed at least 12 weeks of topiramate treatment
were included in the data analysis. RESULTS: Of 55 patients screened, 40 subjects
entered the topiramate treatment period and 21 subjects received at least 12
weeks of treatment. Mean final dose of topiramate was 124 mg per day (range 50 to
200 mg per day). During the baseline period, the mean percentage of attacks
rendered pain-free at 2 hours for the 21 subjects was 46.9% (SD = 31.9), while
during the topiramate treatment period it was 44.6% (SD = 32.2) (P= .8). On
topiramate, after the first 8 weeks of dosage titration, patients experienced a
mean of 3.68 migraine attacks/month, compared to 4.31 during the baseline period
(P < .03). Thirteen subjects discontinued because of adverse events. The most
commonly reported adverse events were paresthesia, fatigue, anxiety, and
dizziness. CONCLUSION: Although topiramate prophylaxis did reduce migraine attack
frequency, in this pilot study topiramate prophylactic migraine treatment did not
increase the proportion of patients pain-free 2 hours after symptomatic triptan
therapy.
PMID- 17040340
TI - Visual stimuli are common triggers of migraine and are associated with pattern
glare.
AB - OBJECTIVE: To investigate the associations between interictal pattern glare,
visual stress, and visual triggers of migraine. BACKGROUND: There has been
relatively little research on the visual stimuli that can trigger migraine
episodes. This is surprising, since if practitioners can obviate such triggers,
then some attacks may be prevented. The existing literature suggests that
patients who are prone to visually triggered migraines report more illusions on
viewing striped patterns ("pattern glare") and that colored filters may be an
effective intervention for these people. METHODS: Headache symptoms and headache
triggers were investigated in migraine and control groups in 2 separate
experiments. In one experiment, we also determined, for each participant, pattern
glare, whether it was reduced by colored filters and, if so, what the optimum
color of filter was. Color vision was also assessed with the D15 test. RESULTS:
People with migraine saw significantly more illusions on viewing each striped
pattern and experienced greater pattern glare. They were also more likely to
select a colored filter to aid visual comfort, particularly colors in the blue-to
green sector of the spectrum. Color vision was impaired subtly but significantly
in migraine. Principal component analyses grouped common headache triggers into 5
broadly equal components: food, visual triggers, alcohol, stress and tiredness,
and the environment. In a second analysis, the overall number of illusions seen
in striped patterns was associated with visual triggers while pattern glare, use
of colored filters, and interictal light sensitivity together formed a sixth
component interpreted as visual stress. CONCLUSIONS: It is suggested that
clinicians should ask migraine patients whether visual stimuli trigger their
migraine, about interictal visual symptoms, and use the pattern glare test to
ensure that those who may benefit from optometric interventions are appropriately
managed.
PMID- 17040341
TI - Treatment of headaches in the ED with lower cervical intramuscular bupivacaine
injections: a 1-year retrospective review of 417 patients.
AB - OBJECTIVE: The primary objective of this retrospective chart review is to
describe 1 year's experience of an academic emergency department (ED) in treating
a wide spectrum of headache classifications with intramuscular injections of 0.5%
bupivacaine bilateral to the spinous process of the lower cervical vertebrae.
BACKGROUND: Headache is a common reason that patients present to an ED. While
there are a number of effective therapeutic interventions available for the
management of headache pain, there clearly remains a need for other treatment
options. The intramuscular injection of 1.5 mL of 0.5% bupivacaine bilateral to
the sixth or seventh cervical vertebrae has been used to treat headache pain in
our facility since July 2002. The clinical setting for the study was an academic
ED with an annual volume of over 75,000 patients. METHODS: We performed a
retrospective review of over 2805 ED patients with the discharge diagnosis of
headache and over 771 patients who were coded as having had an anesthetic
injection between June 30, 2003 and July 1, 2004. All adult patients who had
undergone paraspinous intramuscular injection with bupivacaine for the treatment
of their headache were gleaned from these 2 larger databases and were included in
this retrospective chart review. A systematic review of the medical records was
accomplished for these patients. RESULTS: Lower cervical paraspinous
intramuscular injections with bupivacaine were performed in 417 patients.
Complete headache relief occurred in 271 (65.1%) and partial headache relief in
85 patients (20.4%). No significant relief was reported in 57 patients (13.7%)
and headache worsening was described in 4 patients (1%). Overall a therapeutic
response was reported in 356 of 417 patients (85.4%). Headache relief was
typically rapid with many patients reporting complete headache relief in 5 to 10
minutes. Associated signs and symptoms such as nausea, vomiting, photophobia,
phonophobia, and allodynia were also commonly relieved. CONCLUSION: Our
observations suggest that the intramuscular injection of small amounts of 0.5%
bupivacaine bilateral to the sixth or seventh cervical spinous process appears to
be an effective therapeutic intervention for the treatment of headache pain in
the outpatient setting.
PMID- 17040342
TI - Reversible anorgasmia with topiramate therapy for headache: a report of 7
patients.
AB - OBJECTIVE: To describe 7 patients who developed new onset anorgasmia while using
topiramate therapy for migraine prophylaxis. BACKGROUND: Topiramate is an
effective drug for the prevention of migraine headaches. Though it is generally
well tolerated, it may be associated with a dose-related anorgasmia. METHODS:
Case reports. RESULTS: Seven patients (5 women, 2 men), between the ages of 40
and 62, developed anorgasmia while using topiramate for headache prevention. Four
women and 2 men had migraine without aura, and 1 woman had migraine with aura.
None had a prior history of anorgasmia or sexual dysfunction. Doses associated
with this side effect ranged from 45 to 200 mg daily. All subjects had symptom
resolution. Six patients had resolution within 7 days of discontinuing or
decreasing the medication; the exact time frame of resolution for the seventh
patient is unknown. CONCLUSION: In our series, anorgasmia was a reversible, dose
related adverse effect of topiramate. Physicians need to be aware of the
potential for topiramate to cause sexual side effects, and should inquire about
these symptoms in patients for whom this agent has been prescribed.
PMID- 17040343
TI - An engineer's 6-year headache diary.
PMID- 17040344
TI - Intracranial hypotension following chiropractic spinal manipulation.
AB - We report a case of intracranial hypotension caused by chiropractic manipulation
which, in contrast to previously reported cases, documents the location of the
cerebrospinal fluid leak by radionuclide cisternography. Cervical spinal
manipulation produced a remote lumbar dural tear in our patient. Spinal magnetic
resonance imaging may falsely localize the dural tear in this condition. Although
conservative management is often sufficient, precise localization is required for
more invasive therapies.
PMID- 17040345
TI - Trigeminal neuralgia in wind musicians.
AB - The author reports 3 patients with trigeminal neuralgia whose pain was triggered
by musical performance. Use of the muscles of embouchure activated the trigger
zone when playing the clarinet, saxophone, flute, piccolo, trombone, or
whistling. In each case, the location of the trigger zone was perioral,
regardless of which division of the trigeminal nerve emanated pain. Trigeminal
neuralgia is a particularly disabling affliction when it occurs in wind
musicians.
PMID- 17040346
TI - Subcortical lesions in migraine: are they related to mitochondrial dysfunction?
PMID- 17040347
TI - Migraine prevention.
PMID- 17040348
TI - Behavioral headache treatment: modest costs, demonstrated long-term
effectiveness.
PMID- 17040351
TI - Time for a medical educational change in time.
PMID- 17040352
TI - Liver biopsy: is it still relevant?
PMID- 17040353
TI - Twenty-year audit of percutaneous liver biopsy in a major Australian teaching
hospital.
AB - BACKGROUND: To examine the changes in indications, patient characteristics,
safety and outcomes in consecutive patients undergoing percutaneous core liver
biopsies in a major Australian teaching hospital over a period of two decades.
METHODS: A retrospective audit was carried out on all percutaneous core liver
biopsies from a single institution between 1996 and 2005. This was combined with
10 years of data already reported on for the years 1986-1995 to detect trends in
indications and outcomes. RESULTS: Medical records from 1398 patients were
included for analysis. Over a 20-year period, the most common indications for
liver biopsy were hepatitis C (37.8%), hepatitis B (26.4%) and abnormal liver
function tests (22.2%). Twelve major complications (1.0%) were seen; 10 episodes
of haemorrhage, 1 bile leak and 1 visceral perforation. Seven of these patients
had an abnormal baseline coagulation profile; a significant risk for major
haemorrhage (P < 0.001), resulting in three deaths. All deaths occurred in
inpatients with major comorbidities. Minor complications occurred in 13.6% of
patients, with multiple passes a significant risk factor. Whereas the overall
major and minor complication rates were independent of operator experience
inadequate specimens were more frequently obtained by the registrar. CONCLUSION:
This large series extending over two decades shows that despite advances in
biopsy techniques, the rates of both minor and major complications remain
significant. Of particular concern are the procedure-related deaths. Identifying
factors that may increase risk requires further scrutiny and careful patient
selection needs to be undertaken.
PMID- 17040355
TI - Access to stroke care units in Australian public hospitals: facts and temporal
progress.
AB - BACKGROUND: There is level I evidence that management of stroke patients in
stroke units (SU) improves outcomes (death and institutionalization) by
approximately 20%. In Australia, there is uncertainty as to the proportion of
incident cases that have access to SU. Recent national and State-based policy
initiatives to increase access to SU have been taken. However, objective evidence
related to SU implementation progress is lacking. The aims of the study were (i)
to determine the number of SU in Australian acute public hospitals in 2004, (ii)
to describe hospitals according to national SU policy criteria and (iii) to
compare results to the 1999 survey to track progress. METHODS: The method used in
the study was a cross-sectional, postal survey technique. The participants were
clinical representatives considered appropriate to describe stroke care within
survey hospitals. RESULTS: The outcome of the study was presence of a SU
according to an accepted definition. Response rate was 261/301 (87%). Sixty-one
sites (23%) had either a SU and/or a dedicated stroke team. Fifty sites claimed
to have a SU (19%). New South Wales with 23 had the most number of SU. Based on
policy criteria, up to 64 sites could have a SU. In 1999, there were 35 public
hospitals with a SU. CONCLUSION: Access to SU in Australian public hospitals
remains low compared with other countries (Sweden, 70%). Implementation
strategies supported by appropriate health policy to improve access are needed.
PMID- 17040356
TI - Comparison and validation of three measures of quality of life in patients with
pulmonary hypertension.
AB - BACKGROUND: Pulmonary hypertension, when advanced, markedly limits exercise
capacity, activities of daily living and quality of life (QoL). No measure of QoL
has yet been validated for the assessment of pulmonary hypertension. The aim of
the study was to compare the validity of the Minnesota Living with Heart Failure
(MLwHF) questionnaire, the Short Form-36 (SF-36) questionnaire and the Australian
Quality of Life (AQoL) measure for assessing pulmonary hypertension treatment.
METHODS: Eighty-three patients were enrolled in three studies of pulmonary
hypertension treatment (treprostinil, bosentan and sildenafil). They were
assessed at baseline and 3 months with the MLwHF questionnaire. Treprostinil and
bosentan groups also had 6 and 12 months' data. Twenty-one patients in the
sildenafil trial completed concurrently, the SF-36 and AQoL measures at baseline
and 3 months. QoL scores were correlated with the 6-min walk test distance, New
York Heart Association functional class and right heart catheter-derived
haemodynamic parameters of the disease for all matching time points and for
changes in scores and clinical measurements over time. RESULTS: The MLwHF and SF
36 scores correlated well with the 6-min walk test distance and New York Heart
Association functional class, but did not correlate with haemodynamic
measurements. MLwHF and SF-36 scores also correlated with the rate of change of
the 6-min walk test distance and New York Heart Association functional class over
time. CONCLUSION: The MLwHF questionnaire and SF-36 are useful tools for the
assessment of QoL in pulmonary hypertension and may be useful in the ongoing
evaluation of QoL in the treatment and study of pulmonary hypertension.
PMID- 17040357
TI - Information sources used by New South Wales cancer clinicians: a qualitative
study.
AB - BACKGROUND: This study identified (i) information sources used by cancer
clinicians to guide pharmacological treatments, (ii) utilization of, and opinions
about, online information sources and (iii) clinicians' ability to access a
specific cancer treatment protocol (escalated bleomycin, etiposide, doxorubicin,
cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) for Hodgkin's
Lymphoma). The work was carried out before activation of the Cancer Institute New
South Wales Standard Cancer Treatment (CI-SCaT) programme. METHODS: We conducted
semistructured interviews with a purposeful sample of senior and junior doctors,
nurses and pharmacists treating adult cancer patients (n = 32) in eight New South
Wales public hospitals. RESULTS: Information seeking processes are context
specific and vary from clinician to clinician and ward to ward. Clinicians use
human, electronic and printed information sources at, or close to, the point of
patient care; however, experienced colleagues are preferred where information is
needed quickly or in unfamiliar clinical situations. Barriers to using online
cancer information are environmental (hardware, connection speeds, time),
personal (poor computer literacy and lack of awareness of appropriate sites) and
economic (costs of journal subscriptions). Just over half of participants were
able to locate a specific cancer protocol and none of these protocols was fully
consistent with CI-SCaT recommendations. CONCLUSION: There is no standardized
approach to the pharmacological treatment of cancer patients in this sample of
New South Wales clinicians. CI-SCaT will fill a gap with respect to standardizing
oncology treatment. However, to ensure maximal CI-SCaT uptake, implementation
plans should harness positive behavioural influences and attempt to modify the
negative forces that act on hospital clinicians in their day-to-day work.
PMID- 17040358
TI - Information from the Internet: attitudes of Australian oncology patients.
AB - BACKGROUND: Patients require accurate information about their illness to make
informed decisions. Many sources of information exist, although reliability is
variable. Our objective was to investigate information seeking behaviour and
attitudes toward health-related information from the Internet in a sample of
Australian oncology patients. METHOD: During their outpatient attendance, 109
patients completed a self-administered paper-pen format questionnaire. They were
required to have a recent cancer diagnosis (<6 months ago) adequate English and
no cognitive impairment. RESULTS: Seventy-four per cent of questionnaires were
returned. The majority of patients (78%) wanted as much information about their
cancer diagnosis as possible and 90% reported receiving adequate information from
their treating team. Despite this, more than half actively searched for
additional information, with 77% using the Internet. Patients were trusting of
information obtained from the Internet. More than half of information searchers
discussed information obtained in their search with a health professional. The
majority of patients did not believe that information searching adversely
affected the doctor-patient relationship. CONCLUSION: Information searching is
common in ambulatory Australian oncology patients, with the Internet being a
frequently used resource. To ensure patients find reliable and relevant
information and to minimize the risk of harm, health professionals involved in
treating oncology patients should provide guidance in finding information sources
and assistance in interpreting the information obtained.
PMID- 17040359
TI - Irritable bowel syndrome.
AB - Conceptually, the irritable bowel syndrome (IBS) has been considered a brain-gut
functional disorder, but this paradigm is under serious challenge. There is
increasing evidence that organic disease of the gastrointestinal tract can be
identified in subsets of patients who fulfil the Rome criteria for IBS. Evidence
for subtle inflammatory bowel disease, serotonin dysregulation, bacterial
overgrowth and central dysregulation continue to accumulate. The underlying
causes of IBS remain to be adequately identified, but postinfectious IBS is a
clear-cut entity. Furthermore, a genetic contribution to IBS also seems likely.
Diagnosis continues to be based on the symptom profile and the absence of alarm
features. A heightened awareness of coeliac disease masquerading as IBS is
becoming accepted. Management remains largely based on symptomatic rather than on
disease-modifying therapy, but this is likely to change in the near future. Here,
recent advances in the pathophysiology and management of IBS are considered.
PMID- 17040360
TI - Bronchiectasis.
AB - Bronchiectasis is generally classified into cystic fibrosis and non-cystic
fibrosis bronchiectasis. This review article describes non-cystic fibrosis
bronchiectasis in adults. Bronchiectasis can be considered a heterogeneous
condition characterized by irreversible airway dilatation with chronic bronchial
infection/inflammation. It remains a common condition and is a major cause of
respiratory morbidity. Many factors are associated with bronchiectasis, but most
commonly patients will have idiopathic disease. Important clinical findings
include chronic productive cough, rhinosinusitis, fatigue and bi-basal crackles.
Patients have usually had symptoms for many years. Diagnosis is confirmed by high
resolution computed tomography scanning using standardized criteria. Spirometry
shows moderate airflow obstruction and there is a high prevalence of bronchial
hyperreactivity. The most common pathogens are non-typeable Haemophilus
influenzae and Pseudomonas aeruginosa. There may be considerable overlap with
other chronic airway diseases. Treatment regimens are still not well defined.
Patients tend to have ongoing symptoms and decline in respiratory function
despite treatment.
PMID- 17040361
TI - Thyroid hormone resistance: the role of mutational analysis.
AB - The finding of increased thyroxine (T4) and tri-iodothyronine (T3) levels in a
patient with normal or increased thyroid-stimulating hormone is unexpected and
presents a differential diagnosis between a thyroid-stimulating hormone-secreting
pituitary adenoma, generalized resistance to thyroid hormone (RTH) and laboratory
artefact. Without careful clinical and biochemical evaluation, errors may occur
in patient diagnosis and treatment. In the case of RTH, mutation of the thyroid
hormone receptor beta gene results in generalized tissue resistance to thyroid
hormone. As the pituitary gland shares in this tissue resistance, euthyroidism
with a normal thyroid-stimulating hormone is usually maintained by increased
thyroid hormones. To date, we have identified eight pedigrees in New Zealand with
mutations in the thyroid hormone receptor beta gene, including two novel
mutations. Mutational analysis of the thyroid hormone receptor beta gene allows
definitive diagnosis of RTH, potentially avoiding the need for protracted and
expensive pituitary function testing and imaging. Mutational analysis also
enables family screening and may help to avoid potential misdiagnosis and
inappropriate treatment.
PMID- 17040362
TI - Acute copper toxicity following copper glycinate injection.
AB - We present a patient who developed multi-organ failure due to severe copper
toxicity following attempted suicide by s.c. injection of copper glycinate. Acute
copper toxicity is rare in the developed world, although it occurs more
frequently in developing world countries, where it is a common mode of suicide.
Acute toxicity usually results from oral ingestion and there are several local
and systemic effects. Specific management can be difficult as there is little
evidence regarding the efficacy of chelating agents in acute toxicity.
PMID- 17040363
TI - Fulminant methicillin-sensitive Staphylococcus aureus infection in a healthy
adolescent, highlighting 'Panton-Valentine leucocidin syndrome'.
AB - A 14-year-old immunocompetent adolescent presented systemically unwell with left
knee septic arthritis. Within several days, disseminated bone and soft tissue
collections became evident, associated with deep venous thrombosis and pulmonary
involvement. Methicillin-sensitive Staphylococcus aureus was isolated, harbouring
Panton-Valentine leucocidin genes. Aggressive antibiotic and surgical therapies
eventually lead to recovery. Intrafamilial spread of the pathogenic isolate was
shown by household screening. This presentation is consistent with 'PVL Syndrome'
and is typical of severe S. aureus infection emerging in young populations
globally.
PMID- 17040364
TI - Diabetic muscle infarction.
PMID- 17040365
TI - Anomalous origin of the right coronary artery from the left anterior descending
artery: a rare subtype of single coronary artery anomaly.
PMID- 17040366
TI - Grey-Turner sign after intra-aortic balloon pump insertion.
PMID- 17040367
TI - Hyperandrogenism in a patient with previous colorectal cancer.
PMID- 17040368
TI - Hepatotoxicity and valproate therapy.
PMID- 17040369
TI - Celecoxib allergies and cross-reactivity.
PMID- 17040370
TI - Australian data do not support current Pharmaceutical Benefits Scheme criteria
for use of tumour necrosis factor-alpha inhibitors in ankylosing spondylitis.
PMID- 17040371
TI - Fluctuating asymmetry and developmental instability in evolutionary biology:
past, present and future.
AB - The role of developmental instability (DI), as measured by fluctuating asymmetry
(FA), in evolutionary biology has been the focus of a wealth of research for more
than half a century. In spite of this long period and many published papers, our
current state of knowledge reviewed here only allows us to conclude that patterns
are heterogeneous and that very little is known about the underlying causes of
this heterogeneity. In addition, the statistical properties of FA as a measure of
DI are only poorly grasped because of a general lack of understanding of the
underlying mechanisms that drive DI. If we want to avoid that this area of
research becomes abandoned, more efforts should be made to understand the
observed heterogeneity, and attempts should be made to develop a unifying
statistical protocol. More specifically, and perhaps most importantly, it is
argued here that more attention should be paid to the usefulness of FA as a
measure of DI since many factors might blur this relationship. Furthermore, the
genetic architecture, associations with fitness and the importance of
compensatory growth should be investigated under a variety of stress situations.
In addition, more focus should be directed to the underlying mechanisms of DI as
well as how these processes map to the observable phenotype. These insights could
yield more efficient statistical models and a unified approach to the analysis of
patterns in FA and DI. The study of both DI and canalization is indispensable to
obtain better insights in their possible common origin, especially because both
have been suggested to play a role in both micro- and macro-evolutionary
processes.
PMID- 17040372
TI - Genetic, physiologic and ecogeographic factors contributing to variation in Homo
sapiens: Homo floresiensis reconsidered.
AB - A new species, Homo floresiensis, was recently named for Pleistocene hominid
remains on Flores, Indonesia. Significant controversy has arisen regarding this
species. To address controversial issues and refocus investigations, I examine
the affinities of these remains with Homo sapiens. Clarification of problematic
issues is sought through an integration of genetic and physiological data on
brain ontogeny and evolution. Clarification of the taxonomic value of various
'primitive' traits is possible given these data. Based on this evidence and using
a H. sapiens morphological template, models are developed to account for the
combination of features displayed in the Flores fossils. Given this overview, I
find substantial support for the hypothesis that the remains represent a variant
of H. sapiens possessing a combined growth hormone-insulin-like growth factor I
axis modification and mutation of the MCPH gene family. Further work will be
required to determine the extent to which this variant characterized the
population.
PMID- 17040373
TI - RNA world - the dark matter of evolutionary genomics.
AB - For a long time, molecular evolutionary biologists have been focused on DNA and
proteins, whereas RNA has lived in the shadow of its famous chemical cousins as a
mere intermediary. Although this perspective has begun to change since genome
wide transcriptional profiling was successfully extended to evolutionary biology,
it still echoes in evolutionary literature. In this mini-review, new developments
of RNA biochemistry and transcriptomics are brought to the attention of
evolutionary biologists. In particular, the unexpected abundance and functional
significance of noncoding RNAs is briefly reviewed. Noncoding RNAs control a
remarkable range of biological pathways and processes, all with obvious fitness
consequences, such as initiation of translation, mRNA abundance, transposon
jumping, chromosome architecture, stem cell maintenance, development of brain and
muscles, insulin secretion, cancerogenesis and plant resistance to viral
infections.
PMID- 17040374
TI - Exploring the evolution of environmental sex determination, especially in
reptiles.
AB - Environmental sex determination has been documented in a variety of organisms for
many decades and the adaptive significance of this unusual sex-determining
mechanism has been clarified empirically in most cases. In contrast, temperature
dependent sex determination (TSD) in amniote vertebrates, first noted 40 years
ago in a lizard, has defied a general satisfactory evolutionary explanation
despite considerable research effort. After briefly reviewing relevant theory and
prior empirical work, we draw attention to recent comparative analyses that
illuminate the evolutionary history of TSD in amniote vertebrates and point to
clear avenues for future research on this challenging topic. To that end, we then
highlight the latest empirical findings in lizards and turtles, as well as
promising experimental results from a model organism, that portend an exciting
future of progress in finally elucidating the evolutionary cause(s) and
significance of TSD.
PMID- 17040375
TI - On the logical relationship between natural selection and self-organization.
AB - Most evolutionary biologists cherish Darwin's theory of natural selection (NS) as
the process of adaptive evolution more than 140 years after publication of his
first book on the subject. However, in the past few decades the study of self
organization (SO) in complex dynamical systems has suggested that adaptation may
occur through intrinsic reorganization without NS. In this study, we attempt to
describe the logical framework that relates the general process of SO to the
specific process of NS. We describe NS as a mechanism that coordinates the
coevolution of species in an ecosystem to effectively capture, process and
dissipate solar energy into the earth's shadow. Finally, we conclude that NS is
an emergent process founded on the same thermodynamic imperatives that are
thought to underlie all SO. This perspective suggests that the theory of self
organizing systems offers a broader physical context in which to understand the
process of NS, rather than contesting it. It even suggests the possibility that
there may be a physical basis for understanding the origin of the process of NS.
Rather than being merely a fluke of nature, the origin of NS that may be driven
by energy flows across gradients.
PMID- 17040376
TI - The cost of mating rises nonlinearly with copulation frequency in a laboratory
population of Drosophila melanogaster.
AB - Previous studies of Drosophila melanogaster have demonstrated a cost to females
from male courtship and mating, but two critically important parameters remain
unresolved: (i) the degree to which harm from multiple-mating reduces lifetime
fitness and (ii) how harm from mating might change with successive matings
(rematings). Here we use 'laboratory island analysis' to quantify the costs that
females incur with each remating, in the currency of lifetime fitness and under
conditions that closely match those to which the flies have adapted for hundreds
of generations. We experimentally manipulated the number of female matings by
varying the order of daily 2-h exposures of females to either sperm-less males
(XO) or intact males (XY). Females that mated more often had substantially
reduced lifetime fecundity, and importantly, the fitness cost from remating
rapidly accelerated.
PMID- 17040377
TI - Contrasting patterns of body shape and neutral genetic divergence in marine and
lake populations of threespine sticklebacks.
AB - Comparisons of neutral marker and quantitative trait divergence can provide
important insights into the relative roles of natural selection and neutral
genetic drift in population differentiation. We investigated phenotypic and
genetic differentiation among Fennoscandian threespine stickleback (Gasterosteus
aculeatus) populations, and found that the highest degree of differentiation
occurred between sea and freshwater habitats. Within habitats, morphological
divergence was highest among the different freshwater populations. Pairwise
phenotypic and neutral genetic distances among populations were positively
correlated, suggesting that genetic drift may have contributed to the
morphological differentiation among habitats. On the other hand, the degree of
phenotypic differentiation (PST) clearly surpassed the neutral expectation set by
FST, suggesting a predominant role for natural selection over genetic drift as an
explanation for the observed differentiation. However, separate PST/FST
comparisons by habitats revealed that body shape divergence between lake and
marine populations, and even among marine populations, can be strongly influenced
by natural selection. On the other hand, genetic drift can play an important role
in the differentiation among lake populations.
PMID- 17040378
TI - Substantial changes in the genetic basis of tadpole morphology of Rana lessonae
in the presence of predators.
AB - Predator-induced morphological plasticity is a model system for investigating
phenotypic plasticity in an ecological context. We investigated the genetic basis
of the predator-induced plasticity in Rana lessonae by determining the pattern of
genetic covariation of three morphological traits that were found to be induced
in a predatory environment. Body size decreased and tail dimensions increased
when reared in the presence of preying dragonfly larvae. Genetic variance in body
size increased by almost an order of magnitude in the predator environment, and
the first genetic principal component was found to be highly significantly
different between the two environments. The across environment genetic
correlation for body size was significantly below 1 indicating that different
genes contributed to this trait in the two environments. Body size may therefore
be able to respond to selection independently in the two environments to some
extent.
PMID- 17040379
TI - Reproductive tradeoffs and yolk steroids in female leopard geckos, Eublepharis
macularius.
AB - Life history theory predicts tradeoffs among reproductive traits, but the
physiological mechanisms underlying such tradeoffs remain unclear. Here we
examine reproductive tradeoffs and their association with yolk steroids in an
oviparous lizard. Female leopard geckos lay two eggs in a clutch, produce
multiple clutches in a breeding season, and reproduce for several years. We
detected a significant tradeoff between egg size and the number of clutches laid
by females during their first two breeding seasons. Total reproductive effort was
strongly condition-dependent in the first season, but much less so in the second
season. Although these and other tradeoffs were unmistakable, they were not
associated with levels of androstenedione, oestradiol, or testosterone in egg
yolk. Female condition and egg size, however, were inversely related to
dihydrotestosterone (DHT) levels in egg yolk. Finally, steroid levels in egg yolk
were not directly related to steroid levels in the maternal circulation when
follicles were developing, indicating that steroid transfer to eggs is regulated.
These findings suggest that maternal allocation of DHT could mitigate tradeoffs
that lead to poor offspring quality (i.e. poor female condition) and small
offspring size (i.e. small egg size).
PMID- 17040380
TI - Postzygotic incompatibilities between the pupfishes, Cyprinodon elegans and
Cyprinodon variegatus: hybrid male sterility and sex ratio bias.
AB - I examined the intrinsic postzygotic incompatibilities between two pupfishes,
Cyprinodon elegans and Cyprinodon variegatus. Laboratory hybridization
experiments revealed evidence of strong postzygotic isolation. Male hybrids have
very low fertility, and the survival of backcrosses into C. elegans was
substantially reduced. In addition, several crosses produced female-biased sex
ratios. Crosses involving C. elegans females and C. variegatus males produced
only females, and in backcrosses involving hybrid females and C. elegans males,
males made up approximately 25% of the offspring. All other crosses produced
approximately 50% males. These sex ratios could be explained by genetic
incompatibilities that occur, at least in part, on sex chromosomes. Thus, these
results provide strong albeit indirect evidence that pupfish have XY chromosomal
sex determination. The results of this study provide insight on the evolution of
reproductive isolating mechanisms, particularly the role of Haldane's rule and
the 'faster-male' theory in taxa lacking well-differentiated sex chromosomes.
PMID- 17040381
TI - A broad-scale analysis of population differentiation for Zn tolerance in an
emerging model species for tolerance study: Arabidopsis halleri (Brassicaceae).
AB - Although current knowledge about the overall distribution of zinc (Zn) tolerance
in Arabidopsis halleri populations is scarce, the species is an emerging model
for the study of heavy metal tolerance in plants. We attempted to improve this
knowledge by testing the Zn tolerance of scattered European metallicolous (M) and
nonmetallicolous (NM) populations of A. h. subsp. halleri and A. h. subsp.
ovirensis in hydroponic culture. The occurrence of constitutive tolerance was
unconditionally established in A. h. halleri and tolerance was extended to the
subspecies ovirensis. M populations were the most tolerant but there was a
continuous range of variation in tolerance from NM to M populations. Finally,
relatively high levels of tolerance were detected in some NM populations,
suggesting that enhanced tolerance could be present at high frequency in
populations that have not experienced metal exposure. We used our results to
argue the evolutionary dynamics and origin of Zn tolerance in A. halleri.
PMID- 17040382
TI - Fitness effects of X chromosome drive in the stalk-eyed fly, Cyrtodiopsis
dalmanni.
AB - Sex-ratio (SR) males produce predominantly female progeny because most Y
chromosome sperm are rendered nonfunctional. The resulting transmission advantage
of XSR chromosomes should eventually cause population extinction unless
segregation distortion is masked by suppressors or balanced by selection. By
screening male stalk-eyed flies, Cyrtodiopsis dalmanni, for brood sex ratio we
found unique SR alleles at three X-linked microsatellite loci and used them to
determine if SR persists as a balanced polymorphism. We found that XSR/XST
females produced more offspring than other genotypes and that SR males had lower
sperm precedence and exhibited lower fertility when mating eight females in 24 h.
Adult survival was independent of SR genotype but positively correlated with eye
span. We infer that the SR polymorphism is likely maintained by a combination of
weak overdominance for female fecundity and frequency dependent selection acting
on male fertility. Our discovery of two SR haplotypes in the same population in a
10-year period further suggests that this SR polymorphism may be evolving
rapidly.
PMID- 17040383
TI - Phenotypic plasticity in two marine snails: constraints superseding life history.
AB - In organisms encountering predictable environments, fixed development is
expected, whereas in organisms that cannot predict their future environment,
phenotypic plasticity would be optimal to increase local adaptation. To test this
prediction we experimentally compared phenotypic plasticity in two rocky-shore
snail species; Littorina saxatilis releasing miniature snails on the shore, and
Littorina littorea releasing drifting larvae settling on various shores,
expecting L. littorea to show more phenotypic plasticity than L. saxatilis. We
compared magnitude and direction of vectors of phenotypic difference in juvenile
shell traits after 3 months exposure to different stimuli simulating sheltered
and crab-rich shores, or wave-exposed and crab-free shores. Both species showed
similar direction and magnitude of vectors of phenotypic difference with minor
differences only between ecotypes of the nondispersing species, indicating that
plasticity is an evolving trait in L. saxatilis. The lack of a strong plastic
response in L. littorea might be explained by limits rather than costs to
plasticity.
PMID- 17040384
TI - Sperm competition in a fish with external fertilization: the contribution of
sperm number, speed and length.
AB - The role of sperm number and quality in male competitiveness was investigated
using in vitro fertilization experiments with bluegill (Lepomis macrochirus).
Bluegill males use one of three mating tactics: 'sneakers', which streak spawn;
'satellites', which mimic females; and 'parentals', which are territorial. The in
vitro experiments mimicked natural spawning by incorporating these males' mean
proximity to eggs and timing of sperm release. Using a maximum-likelihood
algorithm, raffle equations were fit to paternity data, which revealed a strong
effect of sperm number on male competitiveness. There was no difference in sperm
flagellum length, curvilinear swim speed or path linearity among the three male
mating types, and these traits did not explain any additional variation in male
competitiveness. It was estimated that, given closer proximity to eggs,
satellites need release only 0.34 times as many sperm as parentals to obtain
equal paternity. Despite being farther from the eggs and releasing sperm about
half a second after parentals, sneakers need only release 0.58 times as many
sperm as parentals to obtain equal paternity. Thus, the increased competitiveness
of sneakers' sperm must come from a component of sperm quality other than speed
or length.
PMID- 17040385
TI - Genetics of host plant use and life history in the comma butterfly across Europe:
varying modes of inheritance as a potential reproductive barrier.
AB - Comma butterflies (Nymphalidae: Polygonia c-album L.) from one Belgian site and
three Spanish sites were crossed with butterflies from a Swedish population in
order to investigate inheritance of female host plant choice, egg mass and larval
growth rate. We found three different modes of inheritance for the three
investigated traits. In line with earlier results from crosses between Swedish
and English populations, the results regarding female oviposition preference
(choice between Urtica dioica and Salix caprea) showed X-linked inheritance to be
of importance for the variation between Sweden and the other sites. Egg mass and
growth rate did not show any sex-linked inheritance. Egg mass differences between
populations seem to be controlled mainly by additive autosomal genes, as hybrids
showed intermediate values. The growth rates of both hybrid types following
reciprocal crossings were similar to each other but consistently higher than for
the two source populations, suggesting a nonadditive mode of inheritance which is
not sex-linked. The different modes of inheritance for host plant preference vs.
important life history traits are likely to result in hybrids with unfit
combinations of traits. This type of potential reproductive barrier based on
multiple ecologically important traits deserves more attention, as it should be a
common situation for instance in the early stages of population divergence in
host plant usage, facilitating ecological speciation.
PMID- 17040386
TI - Male Drosophila melanogaster have higher mating success when adapted to their
thermal environment.
AB - Adaptation to new environments is a well-documented phenomenon. Individuals from
populations maintained in a particular environment for multiple generations tend
to be better able to survive and/or reproduce in that environment than their
ancestors or other individuals adapted to alternative environments. A third major
component of fitness, mating success, has not been well studied in replicated
populations under selection in divergent environments. In this study, we used
mating trials to compare the mating success of male Drosophila melanogaster
adapted for 10 years to two different temperatures, 18 and 25 degrees C. In
competition for female partners, males had significantly higher mating success at
their adapted temperature compared with males adapted to a different temperature.
These results are consistent with the notion that those mutations favoured by
natural selection also tend to be favoured by sexual selection.
PMID- 17040387
TI - Rapid increase in cuckoo egg matching in a recently parasitized reed warbler
population.
AB - Parasitic cuckoos lay eggs that mimic those of their hosts, and such close
phenotypic matching may arise from coevolutionary interactions between parasite
and host. However, cuckoos may also explicitly choose hosts in a way that
increases degree of matching between eggs of cuckoos and parasites, with female
preference for specific host phenotypes increasing the degree of matching. We
tested for temporal change in degree of matching between eggs of the parasitic
European cuckoo (Cuculus canorus) and its reed warbler (Acrocephalus scirpaceus)
host during 24 consecutive years in a recently parasitized reed warbler
population. Cuckoo-host egg matching in an ultraviolet-brownness component
yielding most of the chromatic variance of eggs improved during the study period.
Improved matching was not due to changes in cuckoo egg phenotype. Cuckoo eggs
matched host eggs for ultraviolet-brownness within nests irrespective of duration
of sympatry. Ultraviolet-brownness of cuckoo eggs was similar to that of reed
warbler eggs at parasitized nests, but differed from that of reed warbler eggs at
unparasitized nests. These findings provide tentative support for the cuckoo
preference hypothesis suggesting that cuckoo-host egg matching could partially be
due to cuckoo females selecting host nests based on the appearance of their eggs.
PMID- 17040388
TI - Is size-assortative mating important for rapid pigment differentiation in a
freshwater isopod?
AB - Identifying mechanisms behind assortative mating is central to the understanding
of ecological divergence and speciation. Recent studies show that populations of
the freshwater isopod Asellus aquaticus can rapidly become locally differentiated
when submerged Chara vegetation expands in lakes. In the novel Chara habitat,
isopods have become lighter pigmented and smaller than in ancestral reed stands.
In this study, we used a laboratory multiple-choice experiment to investigate
assortative mating as a possible prezygotic reproductive barrier between Chara
and reed isopods. Mating was assortative when Chara isopods were experimentally
mixed with isopods from an adjacent reed site with large-size individuals,
suggesting a partial prezygotic reproductive barrier. No deviation from random
mating could, however, be detected when Chara isopods were mixed with smaller
sized isopods from another reed site. In both experiments, assortative mating was
apparently based on size, as Chara isopods were larger and reed isopods smaller
in mixed pairs than in assortative pairs. Pigmentation did not have any clear
influence on mating. We suggest that divergence in pigmentation evolved through
natural selection in conjunction with size-assortative mating indirectly causing
assortative mating between Chara and reed isopods. Size-assortative mating is
likely a by-product of natural selection, but its importance may hypothetically
be transient, if selection erodes the correlation between pigmentation and size
over time.
PMID- 17040389
TI - The importance of growth and mortality costs in the evolution of the optimal life
history.
AB - A central assumption of life history theory is that the evolution of the
component traits is determined in part by trade-offs between these traits.
Whereas the existence of such trade-offs has been well demonstrated, the relative
importance of these remains unclear. In this paper we use optimality theory to
test the hypothesis that the trade-off between present and future fecundity
induced by the costs of continued growth is a sufficient explanation for the
optimal age at first reproduction, alpha, and the optimal allocation to
reproduction, G, in 38 populations of perch and Arctic char. This hypothesis is
rejected for both traits and we conclude that this trade-off, by itself, is an
insufficient explanation for the observed values of alpha and G. Similarly, a
fitness function that assumes a mortality cost to reproduction but no growth cost
cannot account for the observed values of alpha. In contrast, under the
assumption that fitness is maximized, the observed life histories can be
accounted for by the joint action of trade-offs between growth and reproductive
allocation and between mortality and reproductive allocation (Individual Juvenile
Mortality model). Although the ability of the growth/mortality model to fit the
data does not prove that this is the mechanism driving the evolution of the
optimal age at first reproduction and allocation to reproduction, the fit does
demonstrate that the hypothesis is consistent with the data and hence cannot at
this time be rejected. We also examine two simpler versions of this model, one in
which adult mortality is a constant proportion of juvenile mortality
[Proportional Juvenile Mortality (PJM) model] and one in which the
proportionality is constant within but not necessarily between species [Specific
Juvenile Mortality (SSJM) model]. We find that the PJM model is unacceptable but
that the SSJM model produces fits suggesting that, within the two species
studied, juvenile mortality is proportional to adult mortality but the value
differs between the two species.
PMID- 17040390
TI - Adaptive evolution of the Bordetella autotransporter pertactin.
AB - The virulence factor pertactin is expressed by the closely related pathogens
Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.
Pertactin is an autotransporter involved in adherence of Bordetella species to
the lung epithelium of mammalian hosts, and it is an important component of most
current acellular pertussis vaccines. These three species produce immunologically
distinct pertactin molecules, resulting in a lack of cross-protection against B.
parapertussis and probably also against B. bronchiseptica. Variation in pertactin
is not only inter-specific, but also occurs between isolates from the same
species. Knowledge about codons that are under positive selection could
facilitate the development of more broadly protective vaccines. Using different
nucleotide substitution models, pertactin genes from B. bronchiseptica, B.
parapertussis and B. pertussis were compared, and positively selected codons were
identified using an empirical Bayesian approach. This approach yielded 15 codons
predicted to be under diversifying selection pressure. These results were
interpreted in an immunological context and may help in improving future
pertussis vaccines.
PMID- 17040391
TI - On the track of the Red Queen: bark beetles, their nematodes, local climate and
geographic parthenogenesis.
AB - Geographic parthenogenesis has been explained as resulting from parasite pressure
(Red Queen hypothesis): several studies have found high degrees of sexuals where
the prevalence of parasites is high. However, it is important to address whether
prevalence of parasites mirrors risk of infection. We explored geographic
parthenogenesis of Ips acuminatus bark beetles and their nematodes. Local climate
is crucial for nematode stages outside the host, in spring and summer, and
prevalence should thus be associated with those temperatures if prevalence
reliably reflects exposure risk across populations. This was the case; however,
high prevalence of a virulent nematode species was not associated with many
sexuals, whereas highly sexual populations were characterized by high infection
risk of benign nematodes. Low virulence of the latter makes Red Queen dynamics
unlikely. Geographical patterns of parthenogenesis were instead associated with
winter temperature and variance in temperature.
PMID- 17040392
TI - Resistance in introduced populations of a freshwater snail to native range
parasites.
AB - Introduced species provide an opportunity to examine responses to novel
ecological conditions, in particular to the absence of co-evolved enemies.
Introduced populations could evolve lower investment in resistance or could down
regulate their immune system as a plastic response to enemy absence. The response
might have consequences for the success of introduced species. Assuming a trade
off between resistance and traits related to demographic success, an evolved
change or reallocation from resistance could increase the chances of invasions.
On the other hand, introduced populations could have increased resistance as a
correlate of greater vigour and competitive ability among successful invaders
[Sampling Bias hypothesis (SBH)]. These hypotheses make different predictions
about investment in resistance in introduced populations. Using a New Zealand
clonal snail (Potamopyrgus antipodarum), we examined the resistance of three
introduced genotypes (one from the US and two from Europe) to several populations
of a native range parasite (Microphallus sp.). One genotype (Euro A) was
resistant to all native range parasite populations, consistent with the SBH.
However, two remaining genotypes (Euro C and US 1) were less susceptible to
parasite populations that were allopatric to their source populations.
Furthermore, resistance of one genotype (US 1) collected from the introduced
range was indistinguishable from its resistance when collected from the range of
the parasite. Hence, there was no evidence for decreased resistance in the
absence of native enemies, which is inconsistent with hypotheses that envision
reduced allocation to resistance or a trade-off between competitive ability and
resistance.
PMID- 17040393
TI - Relative number of generations of hosts and parasites does not influence parasite
local adaptation in coevolving populations of bacteria and phages.
AB - A potential consequence of host-parasite coevolution in spatially structured
populations is parasite local adaptation: local parasites perform better than
foreign parasites on their local host populations. It has been suggested that the
generally shorter generation times of parasites compared with their hosts
contributes to parasites, rather than hosts, being locally adapted. We tested the
hypothesis that relative generation times of hosts and parasites affect local
adaptation of hosts and parasites, using the bacterium Pseudomonas fluorescens
and a lytic phage as host and parasite, respectively. Generation times were not
directly manipulated, but instead one of the coevolving partners was regularly
removed and replaced with a population from an earlier time point. Thus, one
partner underwent more generations than the other. Manipulations were carried out
at both early and later periods of coevolutionary interactions. At early stages
of coevolution, host and parasites that underwent relatively more generations
displayed higher levels of resistance and infectivity, respectively. However, the
relative number of generations that bacteria and phages underwent did not change
the level of local adaptation relative to control populations. This is likely
because generalist hosts and parasites are favoured during early stages of
coevolution, preventing local adaptation. By contrast, at later stages
manipulations had no effect on either average levels of resistance or
infectivity, or alter the level of local adaptation relative to the controls,
possibly because traits other than resistance and infectivity were under strong
selection. Taken together, these data suggest that the relative generation times
of hosts and parasites may not be an important determinant of local adaptation in
this system.
PMID- 17040394
TI - Increased male mating rate in Drosophila is associated with Wolbachia infection.
AB - The maternally inherited bacterium Wolbachia pipientis infects 25-75% of
arthropods and manipulates host reproduction to improve its transmission. One way
Wolbachia achieves this is by inducing cytoplasmic incompatibility (CI), where
crosses between infected males and uninfected females are inviable. Infected
males suffer reduced fertility through CI and reduced sperm production. However,
Wolbachia induce lower levels of CI in nonvirgin males. We examined the impact of
Wolbachia on mating behaviour in male Drosophila melanogaster and D. simulans,
which display varying levels of CI, and show that infected males mate at a higher
rate than uninfected males in both species. This may serve to increase the spread
of Wolbachia, or alternatively, may be a behavioural adaptation employed by males
to reduce the level of CI. Mating at high rate restores reproductive
compatibility with uninfected females resulting in higher male reproductive
success thus promoting male promiscuity. Increased male mating rates also have
implications for the transmission of Wolbachia.
PMID- 17040395
TI - MHC class I variation associates with parasite resistance and longevity in
tropical pythons.
AB - Using restriction fragment length polymorphism (RFLP) we identified 26 unique
major histocompatibility complex (MHC) genotypes in 104 water pythons. We
observed a significant independent association between reduced blood parasite
load (Hepatozoon sp.) and python body length/age, presence of a specific RFLP
fragment (C-fragment) and the overall number of fragments. The parasite has a
negative impact on several python life-history traits such as growth, nutritional
status and longevity. Thus, the C-fragment could be considered a 'good gene' (a
fitness-enhancing genetic element). However, while the number of fragments
affected parasite load, the association between level of parasitaemia and
fragment number was not linear, and, hence, minimum parasite infection level was
achieved at an intermediate number of fragments. Intermediate MHC fragment
numbers were also observed among the largest/oldest pythons, suggesting that both
a specific fragment and intermediate levels of MHC polymorphism enhanced python
longevity. Thus, our results suggest python MHC is subject to both frequency
dependent and balancing selection.
PMID- 17040396
TI - The genetic basis of intrinsic and extrinsic post-zygotic reproductive isolation
jointly promoting speciation in the lake whitefish species complex (Coregonus
clupeaformis).
AB - Understanding the genetic architecture of reproductive barriers and the
evolutionary forces that drove their divergence represents a considerable
challenge towards understanding speciation. The objective of this study was to
determine the genetic basis of intrinsic and extrinsic post-zygotic isolation in
diverging populations of dwarf and normal lake whitefish with allopatric glacial
origins. We found that the rate of embryonic mortality was 5.3-6.5 times higher
in dwarf-normal hybrid backcrosses during development than in F1 dwarf and normal
crosses. When comparing embryos that died during development against larvae that
successfully hatched, patterns of Mendelian segregation at 101 loci whose linkage
is known identified 13 loci distributed over seven linkage groups that exhibited
significant shifts in segregation ratios leading to significant segregation
distortion at these loci in the surviving progeny. Controlled crosses and
quantitative trait loci analysis revealed a significant genetic basis for
developmental time until emergence, a trait critical to fish larval survival in
nature. Hatching backcross progeny exhibited asynchronous emergence and
transgressive segregation, suggesting that extrinsic post-zygotic isolation may
select against hybridization in specific environmental contexts. Evidence of a
genetic basis for increased embryonic mortality followed by asynchronous
emergence indicated that intrinsic and extrinsic mechanisms are not mutually
exclusive in the formation and maintenance of reproductive isolation, but may be
jointly promoting population divergence and ultimately speciation.
PMID- 17040397
TI - Variation in the intensity of inbreeding depression among successive life-cycle
stages and generations in gynodioecious Silene vulgaris (Caryophyllaceae).
AB - Inbreeding depression is one of the hypotheses explaining the maintenance of
females within gynodioecious plant populations. However, the measurement of
fitness components in selfed and outcrossed progeny depends on life-cycle stage
and the history of inbreeding. Comparative data indicate that strong inbreeding
depression is more likely to occur at later life-cycle stages. We used
hermaphrodite individuals of Silene vulgaris originating from three populations
located in different valleys in the Swiss Alps to investigate the effect of two
generations of self- and cross-fertilization on fitness components among
successive stages of the life cycle in a glasshouse experiment. We detected
significant inbreeding depression for most life-cycle stages including: the
number of viable and aborted seeds per fruit, probability of germination, above
ground biomass, probability of flowering, number of flowers per plant, flower
size and pollen viability. Overall, the intensity of inbreeding depression
increased among successive stages of the life cycle and cumulative inbreeding
depression was significantly stronger in the first generation (delta
approximately 0.5) compared with the second generation (delta approximately
0.35). We found no evidence for synergistic epistasis in our experiment. Our
finding of more intense inbreeding depression during later stages of the life
cycle may help to explain the maintenance of females in gynodioecious populations
of S. vulgaris because purging of genetic load is less likely to occur.
PMID- 17040398
TI - Thermal evolution of pre-adult life history traits, geometric size and shape, and
developmental stability in Drosophila subobscura.
AB - Replicated lines of Drosophila subobscura originating from a large outbred stock
collected at the estimated Chilean epicentre (Puerto Montt) of the original New
World invasion were allowed to evolve under controlled conditions of larval
crowding for 3.5 years at three temperature levels (13, 18 and 22 degrees C).
Several pre-adult life history traits (development time, survival and competitive
ability), adult life history related traits (wing size, wing shape and wing
aspect ratio), and wing size and shape asymmetries were measured at the three
temperatures. Cold-adapted (13 degrees C) populations evolved longer development
times and showed lower survival at the highest developmental temperature. No
divergence for wing size was detected following adaptation to temperature
extremes (13 and 22 degrees C), in agreement with earlier observations, but wing
shape changes were obvious as a result of both thermal adaptation and development
at different temperatures. However, the evolutionary trends observed for the wing
aspect ratio were inconsistent with an adaptive hypothesis. There was some
indication that wing shape asymmetry has evolutionarily increased in warm-adapted
populations, which suggests that there is additive genetic variation for
fluctuating asymmetry and that it can evolve under rapid environmental changes
caused by thermal stress. Overall, our results cast strong doubts on the
hypothesis that body size itself is the target of selection, and suggest that pre
adult life history traits are more closely related to thermal adaptation.
PMID- 17040399
TI - Frequency-dependent predation and maintenance of prey polymorphism.
AB - In positive frequency-dependent predation, predation risk of an individual prey
correlates positively with the frequency of that prey type. In a number of small
scale experiments individual predators have shown frequency-dependent behaviour,
often leading to the conclusion that a population of such predators could
maintain prey polymorphism. Using simulations, I studied the dynamics of
frequency-dependent predation and prey polymorphism. The model suggests that
persistence of prey polymorphism decreases with increasing number of predators
that show frequency-dependent behaviour, questioning conclusions about
polymorphism based on experiments with few predators. In addition, prey
population size, prey crypsis, difference in crypsis between prey morphs and the
way the behaviour was adjusted affected the persistence of polymorphism. Under
some circumstances prey population remained polymorphic for a shorter time under
frequency-dependent than under frequency-independent predation. This suggests
that although positive frequency-dependent predator behaviour may maintain prey
polymorphism, it is not a sufficient condition for persistent prey polymorphism.
PMID- 17040400
TI - Unicoloniality, recognition and genetic differentiation in a native Formica ant.
AB - Some ants have an extraordinary form of social organization, called
unicoloniality, whereby individuals mix freely among physically separated nests.
This mode of social organization has been primarily studied in introduced and
invasive ant species, so that the recognition ability and genetic structure of
ants forming unicolonial populations in their native range remain poorly known.
We investigated the pattern of aggression and the genetic structure of six
unicolonial populations of the ant Formica paralugubris at four hierarchical
levels: within nests, among nests within the same population, among nests of
populations within the Alps or Jura Mountains and among nests of the two mountain
ranges. Ants within populations showed no aggressive behaviour, but recognized
nonnestmates as shown by longer antennation bouts. Overall, the level of
aggression increased with geographic and genetic distance but was always
considerably lower than between species. No distinct behavioural supercolony
boundaries were found. Our study provides evidence that unicoloniality can be
maintained in noninvasive ants despite significant genetic differentiation and
the ability to discriminate between nestmates and nonnestmates.
PMID- 17040401
TI - Chromosomal basis of viability differences in Tigriopus californicus
interpopulation hybrids.
AB - Crosses between populations of Tigriopus californicus result in backcross and F2
hybrid breakdown for a variety of fitness related measures. The magnitude of this
hybrid breakdown is correlated with evolutionary divergence. We assessed the
chromosomal basis of viability differences in nonrecombinant backcross hybrids
using markers mapped to individual chromosomes. To assess effects of evolutionary
divergence we crossed one population to three different populations: two
distantly related (approximately 18% mitochondrial COI sequence divergence) and
one closely related (approximately 1% mitochondrial COI sequence divergence). We
found that all three interpopulation crosses resulted in significant deviations
from expected Mendelian ratios at a majority of the loci studied. In all but one
case, deviations were due to a deficit of parental homozygotes. This pattern
implies that populations of T. californicus carry a significant genetic load, and
that a combination of beneficial dominance and deleterious homozygote
heterozygote interactions significantly affects hybrid viability. Pairwise tests
of linkage disequilibrium detected relatively few significant interactions. For
the two divergent crosses, effects of individual chromosomes were highly
concordant. These two crosses also showed higher heterozygote excess in females
than males across the vast majority of chromosomes.
PMID- 17040402
TI - The design of complex sexual traits in male barn swallows: associations between
signal attributes.
AB - Variation in the expression of sexually selected traits among individuals is
widely investigated on the premise that these traits evolved to signal male
quality. Significant repeatabilities of sexual signals and their associations
with condition, mating success, survivorship and age may be the signatures of
sexual selection. However, little is known about the relationship between these
sexual attributes. Here we studied 28 acoustic and visual traits in the barn
swallow, Hirundo rustica, that may potentially function in sexual selection.
Based on effect sizes calculated at the between-individual level, we assessed the
relationship between repeatability, condition-dependence, attractiveness, age
dependence and viability indicator value of sexual traits using sexual signals as
the units of analyses. Those traits that showed high within-year repeatability
also showed high between-year repeatability, indicating that between-individual
variation is consistent within and among seasons. In addition, age-dependence of
traits, probably causing between-year variation, was negatively related to
between-year repeatability. Condition-dependence was negatively correlated with
effect sizes for the extent to which traits predicted viability. Therefore,
traits that are positively related to immediate condition are those that are
negatively related to survival, which may be the signature of a trade-off between
current and future reproductive success ultimately reflecting signal reliability.
No other significant relationship was found between trait attributes. We conclude
that multiple sexual signals reflect different aspects of male quality in the
barn swallow.
PMID- 17040405
TI - Serotonin transporter gene polymorphisms in irritable bowel syndrome.
PMID- 17040406
TI - Electrical stimulation - an evolving concept in the treatment of colonic motor
dysfunctions.
AB - Electrical stimulation of digestive organs is a new approach for the treatment of
dismotility-based diseases affecting the gastrointestinal (GI) tract. The most
significant advancement in this field has been obtained with stomach stimulation.
As a result, a fully implantable stimulation system to treat gastroparesis - the
'Enterra' system - is now commercially available. Similarly, electrical
stimulation of the colon may become a valuable alternative to drug therapy and
surgical procedures in the treatment of colonic motor dysfunctions. Over the past
decade, several stimulation patterns to modulate colon motility have been tested
in animal and human models. The results of these studies are reviewed here in
connection with aspects regarding physiological mechanisms activated by
electrical stimulation of the colon.
PMID- 17040407
TI - Assessment of oesophageal emptying in achalasia patients by intraluminal
impedance monitoring.
AB - Oesophageal emptying can be assessed by radiographic and scintigraphic tests with
radiation exposure or by multichannel intraluminal impedance monitoring (MII).
The aim of this study was to evaluate the applicability of MII for the assessment
of oesophageal emptying in achalasia patients. In 10 achalasia patients,
impedance tracings were scored independently by three observers after ingestion
of a 100-mL barium bolus. Bolus clearance time (BCT) and height of barium column
were scored using fluoroscopic images acquired at 20-s intervals. All patients
showed a low baseline impedance level in the distal oesophagus. Air trapping in
the proximal oesophagus was detected in nine patients. BCT on MII was similar to
that on fluoroscopy in 40-70% of the patients. Correlations between height of
barium on fluoroscopy and fluid level on MII were poor to moderate at different
time intervals. Concordance (Kendall's coefficient) between the three observers
for assessment of fluid level on MII was 0.31 (P = 0.04) at 1 and 5 min, 0.26 (P
= 0.08) at 10 and 0.44 (P = 0.01) at 15 min. We conclude that in achalasia
patients, low baseline impedance levels and air entrapment in the proximal
oesophagus limit the value of intraluminal impedance monitoring as a test of
oesophageal emptying.
PMID- 17040408
TI - Ambulatory 24-h oesophageal impedance-pH recordings: reliability of automatic
analysis for gastro-oesophageal reflux assessment.
AB - Oesophageal pH-impedance monitoring allows detection of acid and non-acid gastro
oesophageal reflux (GOR) events. Visual analysis of impedance recording requires
expertise. Our aim was to evaluate the efficacy of an automated analysis for GOR
assessment. Seventy-three patients with suspected GORD underwent 24-h oesophageal
pH-impedance monitoring. Recordings analysis was performed visually (V) and
automatically using Autoscan function (AS) of Bioview software. A symptom index
(SI) > or =50% was considered for a significant association between symptoms and
reflux events. AS analysis detected more reflux events, especially non-acid,
liquid, pure gas and proximal events. Detection of oesophageal acid exposure and
acid reflux events was similar with both analyses. Agreement between V and AS
analysis was good (Kendall's coefficient W > 0.750, P < 0.01) for all parameters.
During pH-impedance studies, 65 patients reported symptoms. As compared to visual
analysis, the sensitivity and specificity of a positive SI determined by AS were
respectively 85.7% and 80% for all reflux events, 100% and 98% for acid reflux
and 33% and 87.5% for non-acid reflux. Despite good agreement with visual
analysis, automatic analysis overestimates the number of non-acid reflux events.
Visual analysis remains the gold standard to detect an association between
symptoms and non-acid reflux events.
PMID- 17040409
TI - Relationship between upper gastrointestinal symptoms and changes in body weight
in a population-based cohort.
AB - Obesity has been associated with increased reporting of gastrointestinal (GI)
symptoms, but whether weight gain or loss causes symptoms is unclear. We studied
the association between changes in body weight and changes in upper GI symptoms.
Prospective cohort study on random samples of Olmsted County, MN residents.
Distinct upper GI symptom complexes [gastro-oesophageal reflux disease (GERD),
chest pain, dyspepsia- pain predominant, dyspepsia-dysmotility] were defined.
Subjects with persistent, new-onset or disappearing symptoms were identified as
cases, subjects with no reported symptoms in any of the surveys served as
controls. Associations were studied in a logistic regression model, using age,
gender, baseline Body Mass Index and somatic symptom score as covariates.
Participants for whom baseline and follow-up data were available (n = 637) had a
median time between surveys of 10.5 years. Baseline body weight was associated
with GERD, chest pain and dyspepsia-pain predominant symptom complexes. An
increase in body weight >10 lb between surveys was associated with new onset of
dyspepsia-dysmotility (OR 5.57, 95% CI 1.91, 16.2). No association was found
between weight loss >10 lb and the studied symptom complexes. Moderate body
weight increases and decreases are generally not associated with upper GI symptom
changes over time in the general population.
PMID- 17040410
TI - Serotonin transporter gene polymorphism and irritable bowel syndrome.
AB - Polymorphisms in the promoter region of the serotonin reuptake transporter (SERT)
gene may underlie the disturbance in gut function in patients with irritable
bowel syndrome (IBS). Association studies of SERT polymorphisms and IBS have
shown diverse results among different countries, which might be due to racial and
subject composition differences. The aim of this study was to assess the
potential association between SERT polymorphisms and IBS in Koreans. A total of
190 IBS patients, who met the Rome II criteria, and 437 healthy controls were
subjected to genotyping. SERT polymorphisms differed in the IBS and control
groups (P = 0.014). The SERT deletion/deletion genotype occurred with greater
frequency in the diarrhoea-predominant IBS group than in the controls. A strong
genotypic association was observed between the SERT deletion/deletion genotype
and diarrhoea-predominant IBS (P = 0.012). None of the clinical symptoms analysed
was significantly associated with the SERT genotypes. The frequency of the SERT
insertion/insertion genotype was much lower than that of the other two genotypes.
A significant association was observed between the SERT polymorphism and IBS,
especially diarrhoea-predominant IBS, suggesting that the SERT gene is a
potential candidate gene involved in IBS in Korea.
PMID- 17040411
TI - Influence of alcohol consumption on IBS and dyspepsia.
AB - The role of alcohol use in irritable bowel syndrome (IBS) and dyspepsia is not
well understood. We hypothesised that people with psychological distress who
drink no alcohol, or excess alcohol, are at increased risk of having IBS or
dyspepsia. Valid gastrointestinal (GI) symptom surveys were mailed to randomly
selected cohorts of community residents. Associations between IBS, dyspepsia and
abdominal pain and alcohol use were assessed using logistic regression adjusted
for a Somatic Symptom Checklist score (SSC). A total of 4390 (80%) responded; of
these, 10.5% reported IBS, 2% dyspepsia and 22% abdominal pain. Alcohol
consumption >7 drinks week(-1) was associated with a greater odds for dyspepsia
(OR 2.3; 95% CI:1.1-5.0) and frequent abdominal pain (OR 1.5; 95% CI: 1.1-2.0)
but not IBS. However, significant interactions among gender, alcohol use and SSC
scores were detected (P < 0.005). In females with a low SSC score, consuming
alcohol > or =7 drinks week(-1) increased the odds of IBS compared to drinking
alcohol moderately. Alcohol consumption was associated with dyspepsia and
abdominal pain. A relationship with IBS was identified when interactions with
somatization and gender were appropriately considered. Whether these associations
are due to the effects of alcohol on the gut, or a common central mechanism
remains to be determined.
PMID- 17040412
TI - Vasoactive intestinal peptide receptor subtypes and signalling pathways involved
in relaxation of human stomach.
AB - Vasoactive intestinal peptide (VIP) relaxes smooth muscle by interacting with
receptors coupled to cAMP- or cGMP-signalling pathways. Their relative
contribution to human gastric relaxation is unknown. This study aimed at
investigating, in terms of biological activity, receptor expression and related
signalling pathways, the action of VIP separately on the human fundus and the
antrum. VIP caused greater relaxation of smooth muscle cells (SMC) and strips of
the antrum presenting on the former a higher efficacy and potency (ED(50): 0.53
+/- 0.17 nmol L(-1)) than on the fundus (ED(50): 3.4 +/- 1.4 nmol L(-1)). On both
fundus and antrum strips, its effect was tetrodotoxin insentitive. Reverse
transcriptase-polymerase chain reaction analysis showed the sole expression of
VPAC2 and natriuretic peptide clearance receptors, with VPAC2 being more abundant
in the antrum. Functional regional differences in receptor-related signalling
pathways were found. Activation of the cAMP-pathway by forskolin or its
inhibition by adenylate cyclase (2'5'-dideoxyadenosine) or kinase (Rp-cAMPs)
inhibitors had more pronounced effects on antrum SMC. Activation of the cGMP
pathway by sodium nitroprusside or its inhibition by guanylate cyclase (LY83583)
or kinase (KT5823) inhibitors had more effects on fundus SMC, on which a higher
expression of endothelial nitric oxide synthase was found. In conclusion,
regional differences in VIP action on human stomach are related to distinct
myogenic properties of SMC of the antrum and the fundus.
PMID- 17040413
TI - Different susceptibilities of spontaneous rhythmicity and myogenic contractility
to intestinal muscularis inflammation in the hapten-induced colitis.
AB - We examined the time-dependent changes in the immunoreactivity of the smooth
muscle region and the accompanying motility disorder in a hapten-induced rat
model of colitis. Histological analysis and myeloperoxidase (MPO) activity
indicated that inflammatory cells infiltrated into the muscle layer at 2 days
after 2,4,6-trinitrobenzenesulphonic acid (TNBS) treatment. The infiltrated
immune cells then gradually decreased in number, but were still present at 14
days. The expression of proinflammatory cytokine mRNAs (TNF-alpha, IL-1beta and
IL-6) and proteins in the muscle layer was increased at 2 days, then began to
decrease, returning to control levels at 14 days. The frequency of spontaneous
rhythmicity was suppressed at 2 and 7 days, and returned to control levels at 14
days. Consistent with these observations, the immunoreactivity of the
interstitial cells of Cajal network was disrupted at 2 and 7 days, which then
gradually reformed at 14 days. On the other hand, the myogenic contractions
induced by high K(+) and carbachol were decreased at 2 days, and were still
inhibited at 14 days. These results suggest that spontaneous rhythmicity
dysfunction may improve more rapidly than myogenic contractility dysfunction in a
hapten-induced rat model of colitis.
PMID- 17040414
TI - Supraspinal control of external anal sphincter motility: effects of vesical
distension in humans and cats.
AB - A pontine centre located near the micturition centre controlling external anal
sphincter (EAS) motility via noradrenergic neurones has been described in cats.
The aim of this study was to determine (i) whether a similar centre controls EAS
motility in humans and (ii) whether this centre is involved in vesico-sphincteric
reflexes in cats and humans. The effects of an alpha-1-adrenoceptor antagonist
(nicergoline) and those of vesical distension on the electrical activity of the
EAS were studied in paraplegic and non-paraplegic volunteers. The effects of
vesical distension by injecting saline at physiological levels on the responses
of the EAS to pudendal nerve stimulation were investigated in intact cats and
cats with nerve sections. In non-paraplegic subjects, nicergoline and vesical
distension abolished the activity of the EAS. These effects were no longer
observed in paraplegic patients. In cats, vesical distension inhibited the reflex
response of the EAS to pudendal nerve stimulation. This vesico-sphincteric
reflex, which was no longer observed in spinal animals, persisted after
nicergoline injection. These findings indicate that in humans, there exists a
supra-spinal centre facilitating the tonic activity of the EAS via noradrenergic
neurones not involved in the inhibitory vesico-sphincteric reflex.
PMID- 17040415
TI - MRI of the stomach in neurogastroenterology.
PMID- 17040417
TI - Outcomes of low-vision services using optometric and multidisciplinary
approaches: a non-randomized comparison.
AB - Consecutive patients (n = 215) who were referred to optometric (55%) or
multidisciplinary (45%) low-vision services and above 50 years of age were
recruited from four hospitals in the Netherlands. They completed two vision
related quality of life questionnaires, the Vision Quality of Life Core Measure
(VCM1) and the Low Vision Quality of Life Questionnaire (LVQOL), before their
first visit with low-vision services and 1 year later. At follow-up, patients
referred to multidisciplinary low-vision services had lower scores on the
mobility subscale of the LVQOL than patients referred to optometric low-vision
services [5.3 points; 95% confidence interval (CI): 0.2-10.5]. Paired sample t
tests for the two groups of patients taken together show improvement for the VCM1
(3.1 points; 95% CI: 0.6-5.6) and deterioration for the basic aspects of vision
(3.5 points; 95% CI: 1.1-5.9) and the mobility (6.6 points; 95% CI: 3.7-9.5)
subscales of the LVQOL. In conclusion, people referred to optometric services
showed less deterioration in mobility than those referred to multidisciplinary
services. No differences were observed for any of the other subscales of the
LVQOL and the VCM1. Future research in this field should include randomized
controlled designs comparing low-vision services with no treatment or placebo.
PMID- 17040418
TI - The effect of font and line width on reading speed in people with mild to
moderate vision loss.
AB - PURPOSE: The aim of this study was to evaluate the effects of print size,
typeface, and line width on reading speed in readers with mild to moderate sight
problems. METHODS: A total of 43 patients, most of whom had mild cataract or
glaucoma with acuity 6/30 or better (median age = 72; range = 24-88 years), read
aloud a selection of texts presented randomly in four sizes (10, 12, 14 and 16
point), for each of four typefaces [Foundry Form Sans (FFS), Helvetica (HV),
Tiresias PCfont (TPC), Times New Roman (TNR)] at a standard line width of 70
characters and a viewing distance of 40 cm. A subset of letter sizes and
typefaces were tested at two additional line widths (35, 90). RESULTS: As
expected, reading speed increased with print size from a median of 144 words min(
1) for 10-point text to 163 words min(-1) for 16-point text (repeated measures
anova, p < 0.0001). There was also a significant effect of typeface with TPC
being read about 8 words min(-1) faster, on average, than the other fonts (159
words min(-1) for TPC vs 151 words min(-1) for the other fonts, p < 0.0001).
However fonts of the same nominal point size were not equivalent in actual size.
When adjusted for the actual horizontal and vertical space occupied, the
advantage of TPC was eliminated. There was no effect of line width (p > 0.3).
Data from the present study were extrapolated to the general population over age
65. This extrapolation indicated that increasing minimum print size from 10
points to 16 points would increase the proportion of the population able to read
fluently (>85 words min(-1)) from 88.0% to 94.4%. CONCLUSION: This study shows
that line width and typeface have little influence on reading speed in people
with mild to moderate sight problems. Increasing the minimum recommended print
size from 10 points to 14 or 16 points would significantly increase the
proportion of the population able to read fluently.
PMID- 17040419
TI - Double-masked randomised placebo-controlled trial of the effect of prismatic
corrections on rate of reading and the relationship with symptoms.
AB - Practitioners' decisions on when to intervene in decompensated heterophoria are
often based on symptoms, which are in some cases an unreliable indicator of
whether an intervention will be helpful. The aim of our study was to determine
when prismatic corrections improve performance at a measure of dynamic visual
function: the Wilkins Rate of Reading Test (WRRT). All participants manifested an
aligning prism (associated heterophoria) on the near Mallett Unit of 0.5Delta or
greater. There were 80 participants, of whom 58 had exophoria, 15 esophoria, and
seven hyperphoria. The effect of the aligning prism on the WRRT was compared with
a control lens using a double-masked randomised design. For exophoria, an
aligning prism of 2Delta and above has a sensitivity of 67% and a specificity of
79% for improving performance at the WRRT by 5% or more. It is not possible from
our data to achieve a good compromise between sensitivity and specificity for the
other types of heterophoria. Patients in the horizontal (but not vertical)
heterophoria groups had significantly more symptoms than a control group. The
patients whose visual performance is improved by prismatic correction are not
necessarily those who report the most symptoms. Our data suggest that exophoric
patients of any age are likely to have improved visual performance with an
intervention if they have an aligning prism of 2Delta or more, even in the
absence of symptoms. We stress that although the Mallett Unit Fixation Disparity
test provides useful information, its results need to be considered in the
overall context of the patient's symptoms, lifestyle, and the results of other
optometric tests. Although this study evaluated prismatic corrections, we note
that interventions for decompensated heterophoria include not only prismatic
corrections, but also eye exercises and refractive modification.
PMID- 17040420
TI - Screening for Meares-Irlen sensitivity in adults: can assessment methods predict
changes in reading speed?
AB - Two methods of assessing candidates for coloured overlays were compared with the
aim of determining which method had the most practical utility. A total of 58
adults were assessed as potential candidates for coloured overlays, using two
methods; a questionnaire, which identified self-reported previous symptoms, and a
measure of perceptual distortions immediately prior to testing. Participants were
classified as normal, Meares-Irlen sensitive, and borderline sensitive. Reading
speed was measured with and without coloured overlays, using the Wilkins Rate of
Reading Test and the change in speed was calculated. Participants classified as
normal did not show any significant benefit from reading with an overlay. In
contrast, a significant reading advantage was found for the borderline and Meares
Irlen participants. Current symptom rating was found to be a significant
predictor of the change in reading speed, however the previous symptom rating was
not found to be a reliable predictor. These data indicate that the assessment of
perceptual distortions immediately prior to measuring colour preference and
reading speed is the most meaningful method of assessing pattern glare and
determining the utility of coloured overlays.
PMID- 17040421
TI - Dynamics in longitudinal eye movements and corneal shape.
AB - The magnitude and character of longitudinal movements of the eye were studied in
the context of high speed videokeratoscopy. It was of interest to determine
whether these dynamic changes in the eye movements can affect the corneal shape
and its estimation. A high speed videokeratoscope with a sampling frequency of 50
Hz was used for measuring the corneal apex movements as well as for measuring
variations in the best-fit sphere radius and central radius of curvature. The
magnitude of the measured longitudinal apex movements could reach over 200 microm
showing a slow trend. The estimated local changes of the apex movements that
could be associated with the cardiopulmonary system were about 40-50 microm. The
temporal variations in the equivalent estimated central radius of curvature
ranged between 10 and 15 microm. Spectral analysis of the longitudinal eye
movements revealed strong signatures of the pulse and respiration signals as well
as the assumed blink control signal. No clear association between the
longitudinal apex movements and the corneal curvature was found. However, very
slow significant changes in the corneal shape were observed. The central radius
of curvature of the cornea revealed slow changes of up to 120 microm.
Understanding the nature of such changes will be of benefit in ophthalmic
applications requiring highly accurate measurements of corneal shape, such as
contact lens design and refractive surgery.
PMID- 17040422
TI - End-box scoring artefact evaluation of the Farnsworth-Munsell 100-Hue colour
vision test.
AB - The scoring artefact in the Farnsworth-Munsell 100-Hue test, arising from the
grouping of the caps into four boxes, was investigated. The traditional method of
scoring performed with the numbers of the anchor caps disregarded and the
alternative scoring performed with the numbers of the anchor caps employed, were
compared. For the traditional method of scoring, we revealed an increase of the
error score of the outside (end-box) caps when the total error score was above
240. On the contrary for scoring performed with the numbers of the anchor caps
employed, the difference between the error score of the outside caps and the
average error per cap is not significant. To mitigate the end-box artefact and to
improve the reliability of the Farnsworth-Munsell 100-Hue test, corrections to
the traditional method of scoring are proposed.
PMID- 17040423
TI - Subtle binocular vision anomalies in migraine.
AB - A literature review reveals old references to an association between migraine
headache and binocular vision anomalies, but a lack of scientific evidence
evaluating these claims. In a masked case control study, we investigated
binocular vision using standard clinical tests in people with migraine and in
controls. Some test results suggest that heterophoria and fixation disparity are
more common in the migraine group. The migraine group also had slightly reduced
stereopsis. We found significant correlations between some migraine variables and
some binocular vision variables (e.g., duration of worst headache and impaired
stereopsis) but our analyses do not suggest that a causal relationship is likely.
In conclusion, people with migraine have on average a slightly higher prevalence
of heterophoria and aligning prism, and reduced stereopsis compared with
controls. However, the differences are subtle and our data do not support the use
of binocular vision interventions prescribed solely on the basis of the presence
of migraine.
PMID- 17040424
TI - Comparison of logMAR ETDRS chart and a new computerised staircased procedure for
assessment of the visual acuity of children.
AB - The validity and repeatability of visual acuity measures are particularly
important in the detection and monitoring of childhood visual anomalies such as
amblyopia. The repeatability and sensitivity of a new computerised visual acuity
test, 'Staircased Procedure' is compared with the now gold standard visual acuity
test, the early treatment of diabetic retinopathy study (ETDRS). Twenty-seven
visually normal children (mean age: 6.7 +/- 1.1 years) and 27 children with
amblyopia (mean age: 6.1 +/- 0.7 years) were tested with the ETDRS and Staircased
Procedure. A retest was administered 4-5 weeks later and 30 min later for the
visually normal and the amblyopic children, respectively. The staircased
procedure produced significantly better visual acuity than the ETDRS for visually
normal and amblyopic children. Repeatability was similar for both tests (ETDRS:
0.11 log units; staircased procedure: 0.13 log units). In conclusion, the
Staircased Procedure was an acceptable test with high repeatability and validity.
PMID- 17040425
TI - Approximating ocular surfaces by generalised conic curves.
AB - Most of the optical models of the human eye use simple conic functions to
represent its individual components such as corneal surfaces and the surfaces of
the crystalline lens. Although a conic function provides an acceptable
approximation for most anatomical eye surfaces, it also leads to a simple optical
analysis of the whole eye system. To fill the gap between the classical use of
conic surfaces and the use of more sophisticated functions that often invoke
numerically expensive procedures in the optical analysis, a functional
generalisation of the conic curve is proposed. A detailed derivation of the
generalised conic function is presented for a two-dimensional (meridional) case.
This is followed by a three-dimensional surface approximation. Examples are given
in which the superiority of the proposed approximation over a classical conic
function as well as the hyperbolic cosine approximation is evident. In
particular, it is shown that for an average total corneal profile, the proposed
generalisation results in a residual height error that is of an order smaller
than those achieved with the conic and hyperbolic cosine approximations. In
conclusion, the proposed generalised conic function can be a useful tool in eye
modelling, where the simplicity of expression is often desirable.
PMID- 17040427
TI - Rituximab: applications in dermatology.
AB - Rituximab is a chimeric anti-CD20 monoclonal antibody which has been used
extensively for B-lymphocytic malignancies. In addition, applications for
autoimmune diseases have emerged in recent years. Case reports support the use of
rituximab in certain dermatologic conditions, including paraneoplastic pemphigus,
pemphigus vulgaris, graft versus host disease, and cutaneous B-cell malignancies.
Clinical trials are lacking and would be an appropriate next step.
PMID- 17040428
TI - Serum eosinophil cationic protein in children with atopic dermatitis.
AB - BACKGROUND: Eosinophil cationic protein (ECP) is a cytotoxic agent secreted by
activated eosinophils during allergic and inflammatory processes. The aim of the
study was to determine the ECP level, absolute and relative eosinophil count and
IgE antibodies in children with atopic dermatitis (AD) compared with those of
nonatopic children, and to assess the correlation of these laboratory parameters
with the clinical severity of AD. METHODS: This prospective study comprised 70
children. There were 49 children with AD aged 3-36 months, and the control group
comprised 21 children with a negative personal and family history for atopic
diseases. Detailed history, serum ECP levels (UniCAP FEIA), relative and absolute
eosinophil counts and total serum IgE antibodies were determined in both groups.
In the children with AD, skin involvement was measured by the SCORAD index.
RESULTS: The calculated SCORAD index was between 16 and 83. IgE antibodies,
relative and absolute eosinophil counts showed a significantly wider range of
values and a statistically higher median (P < 0.001) in the patients with AD
compared with the control group. These laboratory parameters did not correlate
with the severity of AD. The serum ECP median level, in the children with AD, was
16.2 microg/L (range 3.01-65.30) compared with 5.92 microg/L (range 2.76-21.90)
in the control group. Correlation of the total SCORAD index and the serum ECP
levels was negative, weak (r = -0.065) and statistically not significant (P >
0.05). The same was found for the correlation of serum ECP and intensity of skin
changes (r = -0.095) and serum ECP and subjective symptoms (r = -0.045). The
correlation was positive, but weak and statistically not significant for the
serum ECP and extent of the skin lesions (r = 0.079, P > 0.05). CONCLUSION:
Elevated levels of ECP, relative and absolute eosinophil counts, as well as IgE
antibodies were determined in the patients with AD. As these laboratory findings
did not correlate with the severity of AD, they can be considered only as
additional methods in the evaluation of patients with AD.
PMID- 17040429
TI - Self-inflicted garlic burns: our experience and literature review.
AB - BACKGROUND: Throughout history, garlic has been used to treat a large variety of
illnesses. One of garlic's adverse local effects is contact dermatitis. METHODS:
We present three patients treated in the Department of Plastic Surgery for
suspected self-inflicted lower extremity burns. RESULTS: The burns had unique
features, not consistent with the etiology first claimed by the patients. All
were soldiers with low motivation who confessed to using garlic to cause the
burns. CONCLUSIONS: Garlic application usually results in local inflammation,
but, if applied under a pressure bandage, or if there is poor wound care or a
secondary infection, it can cause a severe dermal reaction and a deep chemical
burn. We present these cases to increase physician awareness of the
characteristics of self-inflicted garlic burns, and review the dermatotoxic
effect.
PMID- 17040430
TI - Prurigo pigmentosa: not an uncommon disease in the Turkish population.
AB - BACKGROUND: Prurigo pigmentosa (PP) is a rare inflammatory dermatosis of unknown
etiology. It is characterized by erythematous papules of the trunk that resolve
leaving a reticulate hyperpigmentation. The original report from Japan in 1971
was followed by new cases, mostly of Japanese origin. METHODS: We scrutinized PP
cases diagnosed in our clinic and reviewed the English, German, French, and
Turkish language literature. RESULTS: We report six additional Turkish patients.
We found more than 40 cases reported from various countries outside Japan. The
patients had different racial origins. The number of Turkish patients reported in
recent years is higher than the number of other non-Japanese patients reported.
CONCLUSIONS: The disease is not uncommon in the Turkish population. It may be
underestimated in other countries with Caucasian populations. Therapeutic results
with tetracycline and doxycycline was successful in our patients.
PMID- 17040431
TI - Evaluation of specific antibodies for early diagnosis and management of syphilis.
AB - For many years, tests for cardiolipin antibodies Tp15, Tp17, Tp45, Tp47, and
other specific Treponema pallidum antibodies, have been used to diagnose
syphilis, but the timing and rates of antibody detection differ in primary and
secondary syphilis. Our objective was to determine the value of the rapid plasma
reagin (RPR) test, T. pallidum passive particle agglutination (TPPA) assay and
Western blotting (WB) in the diagnosis of early syphilis, by studying 67 patients
(20 with primary and 47 with secondary syphilis) over a recent 5-year period. All
patients were tested before and 21/67 were tested after treatment. Western
blotting showed that while there was a difference within the study group in terms
of the number of bands detected, all patients with primary syphilis demonstrated
the 47-kDa antibody, but RPR and TPPA were negative in some patients. Eighteen to
24 months after treatment, 21/67 patients were tested by WB and TPPA; antibodies
to T. pallidum became undetectable within 24 months after treatment in 29% of
patients. By RPR, 29% patients had negative titers within 6 months of treatment,
and 86% returned to normal within 24 months. We conclude that detection of
specific 47-kDa T. pallidum antibodies can be used to diagnose primary syphilis.
By RPR, antibodies disappear in 6-24 months after treatment in many patients,
suggesting that a change in titer may be an indicator of treatment success.
PMID- 17040432
TI - Unusual palmoplantar blistering in the setting of hemodialysis: a case report and
review of the dermatoses associated with hemodialysis.
AB - We describe a 70-year-old White female on maintenance high-flux hemodialysis for
chronic renal insufficiency with an abrupt onset of asymptomatic palmoplantar
blisters. The lesions were tense, noninflamed and 0.2-1.0 cm in dimension.
Concomitant photo-distributed blistering of the dorsal hands and forearms was not
present. A cutaneous biopsy demonstrated nonspecific histological and direct
immunofluorescent findings. Serum indirect immunofluorescence and tissue cultures
for bacteria, fungi and viruses were negative. Fecal porphyrins were normal but
an elevated plasma uroporphyrin level of 17.0 microg/dL (normal: < 1.0 microg/dL)
was observed. The duration of each hemodialysis treatment, which the patient had
continued to receive three times per week, was changed from 2 to 2.5 h. Within 2
weeks no new blisters occurred. Within 6 weeks complete clinical and biochemical
remission was noted. During this time course no topical steroid or antifungal
therapy was employed nor was the patient's oral medication regimen altered.
PMID- 17040433
TI - Genetic epidemiology of vitiligo: a study of 815 probands and their families from
south China.
AB - BACKGROUND: Genetic factors are thought to be involved in the development of
vitiligo. AIM: To explore the possible genetic model of vitiligo by analyzing the
genetic characteristics of 815 patients and their families from south China
(Zhejiang Province). METHODS: Data for 815 patients with vitiligo were obtained
by questionnaire. The inheritance pattern estimation, heritability calculation,
and complex segregation analysis were performed using the Penrose method,
Falconer regression method, and SAGE-REGTL program, respectively. RESULTS: In 815
vitiligo probands, 128 (15.7%) had a family history. The ratio of the sibling
prevalence rate to the population prevalence rate (s/q) approached 1/square root
q using the Penrose calculation, and the heritability degrees of vitiligo in the
first- and second-degree relatives were 59.6% and 55.2%, respectively. The
complex segregation analysis suggested that the dominant model was the best-fit
genetic model for vitiligo. CONCLUSIONS: Genetic factors play an important role
in the occurrence of vitiligo, and the genetic model of vitiligo in this
population is consistent with a polygenetic or multifactorial inheritance in a
dominant major gene pattern.
PMID- 17040434
TI - Erosive pustular dermatosis of the leg.
PMID- 17040435
TI - Association of linear IgA bullous disease of childhood with Crohn's disease.
PMID- 17040436
TI - Central trichoptilosis with onycholysis.
PMID- 17040437
TI - Monosymptomatic hypochondriacal psychosis presenting with recurrent oral mucosal
ulcers and multiple skin lesions responding to olanzapine treatment.
AB - Monosymptomatic hypochondriacal psychosis (MHP) is a form of psychosis
characterized by the delusional idea that there is a serious problem in the skin
or other body parts. Because MHP patients believe that their complaint is
dermatological, not psychiatric, they often admit to several other medical
disciplines before coming to a psychiatry clinic. This leads to a series of time
consuming examinations and treatment interventions. In this case report, we
emphasize the importance of diagnosing the illness correctly and referring the
patient to a psychiatrist. The patient presented in this report has been treated
with a new generation neuroleptic, olanzapine. This treatment has led to complete
resolution of delusional symptoms. Therefore, we conclude that knowing that MHP
is a psychiatric illness allows early establishment of diagnosis and successful
treatment.
PMID- 17040438
TI - CD4/CD8 double-positive, acute type of adult T-cell leukemia/lymphoma with
extensive cutaneous involvement.
PMID- 17040439
TI - Trichotillomania or alopecia areata?
PMID- 17040440
TI - Unusual coexistence of molluscum contagiosum and verruca plana in a hyper-IgE
syndrome.
PMID- 17040441
TI - Precalcaneal congenital fibrolipomatous hamartoma.
PMID- 17040442
TI - Cutaneous and pulmonary nocardiosis in pemphigus vulgaris: a rare complication of
immunosuppressive therapy.
PMID- 17040443
TI - Primary amelanotic melanoma of the esophagus.
AB - Primary melanoma of the esophagus (PME) is an uncommon malignancy with less than
250 cases reported in the literature. Amelanotic PME is exceedingly rare and
accounts for 10-25% of melanomas of the esophagus. A 59-year-old male with a
history of mild dysphagia, heartburn, moderate anorexia and weight loss for 1
month is described. Barium swallow examination and videogastroscopy showed a
polypoid, ulcerated mass located 30-38 cm from the incisors. No skin or eye
melanoma lesions were found. Five biopsy samples were obtained. Histological
examinations revealed proliferation of large, loosely cohesive cells of variable
shapes and prominent central nucleoli in the deep mucosa. Immunohistochemical
findings included positive vimentin, protein S-100, Melan A, and HMB-45, and
negative AE1/AE3, CD 17, and desmin. A total transhiatal esophagectomy with high
cervical esophagogastric anastomosis was performed. Peritumoral lymph nodes
revealed malignant invasion. A diagnosis of primary amelanotic melanoma of the
esophagus was made. Fourteen months after diagnosis the patient developed
disseminated PME.
PMID- 17040444
TI - Angiolymphoid hyperplasia with eosinophilia induced by trauma.
PMID- 17040445
TI - Unusual cutaneous findings of urticaria pigmentosa and telangiectasia macularis
eruptiva perstans associated with marked myelofibrosis.
AB - Mastocytosis is a heterogeneous group of disorders characterized by mast cell
hyperplasia in the bone marrow, liver, spleen, lymph nodes, gastrointestinal
tract, and skin. We present a patient with malignant mastocytosis of 11 years'
duration. This case highlights the cutaneous findings of mastocytosis with
systemic involvement, yet the patient maintains a relatively normal lifestyle
with only minimal discomfort and only borderline normochromic anemia. Thus his
course is not truly that of malignant mastocytosis but of indolent systemic
mastocytosis with cutaneous findings of telangiectasia macularis eruptiva
perstans (TMEP).
PMID- 17040446
TI - Syringoid eccrine carcinoma with apparently aggressive transformation: case
report and review of the literature.
PMID- 17040447
TI - Necrotizing fasciitis: delay in diagnosis results in loss of limb.
PMID- 17040448
TI - Treatment of severe chronic idiopathic urticaria with oral mycophenolate mofetil
in patients not responding to antihistamines and/or corticosteroids.
AB - BACKGROUND: Urticarial patients are usually treated with oral antihistamines and
50% respond well to this treatment; however, the other 50% do not respond to
antihistamines and need a more aggressive approach, such as short or prolonged
courses of oral corticosteroids or cyclosporine. Potential adverse effects,
however, limit this regimen. OBJECTIVE: To determine the efficacy of
mycophenolate mofetil, an immunomodulatory drug, in the treatment of patients
with severe chronic urticaria. METHODS: In an open-label, uncontrolled trial,
nine patients with documented chronic urticaria who had been treated previously
with antihistamines and/or corticosteroids with poor response were enrolled in
the trial. After 2 weeks of baseline assessment, patients received 1000 mg twice
daily of mycophenolate mofetil for 12 weeks. Improvement was monitored using the
urticarial activity score, which is the sum of the wheal number score and itch
severity score. Patients also recorded their daily need for other medications to
control allergic symptoms. RESULTS: There was a significant decrease in the
urticarial activity score relative to the baseline assessment at the end of the
study period (P < 0.001). All patients were able to stop prednisone on completion
of the study. There was also a decrease in antihistamine dose, but this did not
reach statistical significance. Treatment with mycophenolate mofetil was not
associated with significant adverse effects. CONCLUSIONS: Mycophenolate mofetil
may be a valuable and safe treatment for patients with chronic urticaria who do
not respond to antihistamines and/or corticosteroids, and who require aggressive
treatment to control their disease symptoms. Further controlled clinical studies
are needed to determine its value.
PMID- 17040449
TI - Contribution of Brazilian dermatologists to the development of dermatology.
PMID- 17040450
TI - Public health dermatology: regeneration and repair of the skin in the developed
transitional and developing world.
PMID- 17040451
TI - Efficacy of isotretinoin in pityriasis rubra pilaris: unapproved use.
PMID- 17040452
TI - Irritant-induced enhancement of induction and elicitation of sensitization for
the treatment of seborrheic keratoses.
PMID- 17040453
TI - Subjective and objective measurement methods in clinical dermatology from an
historical perspective: the long way from Joseph Plenck to validation.
PMID- 17040454
TI - Effective treatment of erosive lichen planus with thalidomide and topical
tacrolimus.
PMID- 17040455
TI - Tetracycline/doxycycline-induced cutaneous depressed pigmentation.
PMID- 17040456
TI - Acute generalized exanthematous pustulosis triggered by intake of herbal
medications.
PMID- 17040457
TI - Heliotrope-like eruption mimicking dermatomyositis in a patient treated with
imatinib mesylate for chronic myeloid leukemia.
PMID- 17040458
TI - Successful treatment of Zoon's balanitis with topical tacrolimus.
PMID- 17040459
TI - Vulvo-vaginal-gingival syndrome of lichen planus.
PMID- 17040460
TI - Bullous Sweet's syndrome following influenza vaccination in a HIV-infected
patient.
PMID- 17040461
TI - Hydroxychloroquine as a treatment for atrophoderma of Pasini and Pierini.
PMID- 17040462
TI - Cytokeratin 7 staining was useful in a case of pigmented mammary Paget's disease
resembling malignant melanoma.
PMID- 17040463
TI - Black piedra: report of a French case associated with Trichosporon asahii.
PMID- 17040464
TI - Toxic epidermal necrolysis caused by tetrazepam.
PMID- 17040465
TI - Chloroquine/hydroxychloroquine-induced pemphigus.
PMID- 17040466
TI - Malignant eccrine poroma presenting with pulmonary and liver metastases.
PMID- 17040467
TI - Treatment of HIV-associated eosinophilic pustular folliculitis with narrow-band
UVB.
PMID- 17040468
TI - Cutaneous schwannoma treated by tumescent suction technique.
PMID- 17040469
TI - Unilesional folliculotropic/syringotropic cutaneous T-cell lymphoma presenting as
an indurated plaque on the nape.
PMID- 17040470
TI - Evaluation of a pharmacotherapy context-learning programme for preclinical
medical students.
AB - AIM: To evaluate a context-learning pharmacotherapy programme for approximately
750 2nd, 3rd and 4th year preclinical medical students with respect to mastering
cognitive pharmacotherapeutic skills, i.e. choosing a (drug) treatment and
determining patient information. METHODS: The context-learning pharmacotherapy
programme consists of weekly organized role play sessions in the form of
consulting hours. Fourth year students sit for a therapeutic Objective Structured
Clinical Examination (OSCE) in the form of consulting hours at the outpatient
clinic. Sixty-one 2nd, 74 3rd and 49 4th year medical students who attended the
role play sessions and the OSCE were randomly selected. Their performances were
assessed by clinical examiners and clinical experts and compared with a reference
group of 6th year graduated students. Additionally, the scores of a questionnaire
on study load and appreciation were collected. RESULTS: The level of the
pharmacotherapeutic skills of the 4th year students who followed the
pharmacotherapy context-learning programme was not far below that of 6th year
graduates who had finished their clinical clerkships, but had not followed the
pharmacotherapy programme. The time spent on the programme was about 1% of the
total study load per year. The students appreciated the role play sessions and
OSCE by around 80% and 99% of the maximum possible scores. CONCLUSIONS:
Preclinical pharmacotherapy context learning has a modest but positive effect on
learning cognitive pharmacotherapeutic skills, i.e. choosing a drug treatment and
determining patient information. This effect has been obtained with role play
sessions, a suboptimal form of context learning, with a minimal study load and a
high appreciation by students.
PMID- 17040471
TI - Relationship of opioid receptors with GABAergic neurons in the rat inferior
colliculus.
AB - The inferior colliculus is a critical structure for processing auditory
information and receives ascending and descending synaptic auditory projections.
In addition to GABAergic and glutamatergic innervations, other neurotransmitter
systems are also reported in the inferior colliculus, including opioid peptides.
In the present study, the relative distribution of each type of opioid receptor,
mu (MOR), delta (DOR) and kappa (KOR) within GABAergic neurons in the inferior
colliculus was examined. GABA immunoreactivity was expressed by small, medium and
large neurons and distributed in the central nucleus and the pericentral nucleus
of the inferior colliculus. Immunostaining for MOR, DOR and KOR receptors was
found in both disc-shaped cells and stellate cells. Punctiform beta-endorphin
immunolabelling was observed in the proximity of GABA-positive neurons. Co
localization of GABA and MOR receptors was observed in neurons and nerve
terminals in the central nucleus, dorsal cortex and external cortex of the
inferior colliculus. Quantification of the co-localization patterns determined
that a higher proportion of GABA neurons was associated with MOR receptors
compared with KOR or DOR receptors.
PMID- 17040472
TI - Effects of nitric oxide-active drugs on the discharge of subthalamic neurons:
microiontophoretic evidence in the rat.
AB - The presence of nitric oxide (NO) synthase and of soluble guanylyl cyclase, the
main NO-activated metabolic pathway, has been demonstrated in many cells of the
subthalamic nucleus. In this study, the effects induced on the firing of 96
subthalamic neurons by microiontophoretically administering drugs modifying NO
neurotransmission were explored in anaesthetized rats. Recorded neurons were
classified into regularly and irregularly discharging on the basis of their
firing pattern. Nomega-nitro-L-arginine methyl ester (L-NAME; a NO synthase
inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1; a NO donor), S-nitroso
glutathione (SNOG; another NO donor) and 8-Br-cGMP (a cell-permeable analogue of
cGMP, the main second-messenger of NO neurotransmission) were iontophoretically
applied while performing single-unit extracellular recordings. The activity of
most neurons was influenced in a statistically significant way: in particular,
both current-related inhibitory L-NAME-induced effects (20/39 tested cells) and
excitatory effects of SIN-1 (25/41 tested neurons), SNOG (19/32 tested cells) and
8-Br-cGMP (13/19 tested neurons) were demonstrated. Neither statistically
significant differences between the responses of regularly and irregularly
discharging cells, nor specific topographical clustering of responding neurons,
were demonstrated. Neurons administered drugs oppositely modulating the NO
neurotransmission often displayed responses to only one treatment. We hypothesize
that NO neurotransmission could exert a modulatory influence upon subthalamic
neurons, with a prevalent excitatory effect. However, in the light of the
presence of some responses of opposite sign to the same drug displayed by
different subthalamic neurons, more complex effects of NO neurotransmission could
be suggested, probably due to interactions with other classical neurotransmitter
systems.
PMID- 17040473
TI - Neuropathic pain and the endocannabinoid system in the dorsal raphe:
pharmacological treatment and interactions with the serotonergic system.
AB - We used a model of neuropathic pain consisting of rats with chronic constriction
injury (CCI) of the sciatic nerve, in order to investigate whether
endocannabinoid levels are altered in the dorsal raphe (DR) and to assess the
effect of repeated treatment with (R)-(+)-[2,3-dihydro-5-methyl-3-(4
morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone
mesylate, a synthetic cannabinoid agonist, or N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z
eicosatetraenamide (AM404), an inhibitor of endocannabinoid reuptake, on DR
serotonergic neuronal activity and on behavioural hyperalgesia. CCI resulted in
significantly elevated anandamide but not 2-arachidonoylglycerol levels in the
DR. Furthermore, as well as thermal and mechanical hyperalgesia, CCI caused
serotonergic hyperactivity (as shown by the increase of basal activity of
serotonergic neurones, extracellular serotonin levels and expression of 5-HT1A
receptor gene). Repeated treatment with either (R)-(+)-[2,3-dihydro-5-methyl-3-(4
morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone
mesylate or AM404 reverted the hyperalgesia and enhanced serotonergic activity
induced by CCI in a way attenuated by N-piperidino-5-(4-chlorophenyl)-1
(2,4dichlorophenyl)-4-methyl-3-pyrazolecarboxamide, a selective cannabinoid
subtype 1 (CB1) receptor antagonist. Despite the elevated levels of anandamide
following CCI, N-piperidino-5-(4-chlorophenyl)-1-(2,4dichlorophenyl)-4-methyl-3
pyrazolecarboxamide did not produce hyperalgesia or any other effect on
serotonergic neuronal activity when administered alone. Furthermore, the effects
of AM404 were not accompanied by an increase in endocannabinoid levels in the DR.
In conclusion, following CCI of the sciatic nerve, the endocannabinoid and
serotonergic systems are activated in the DR, where repeated stimulation of CB1
receptors with exogenous compounds restores DR serotonergic activity, as well as
thermal and mechanical nociceptive thresholds, to pre-surgery levels. However, an
elevated level of endogenous anandamide in the DR does not necessarily contribute
to the CB1-mediated tonic control of analgesia and serotonergic neuronal
activity.
PMID- 17040474
TI - Activation of muscarinic cholinergic receptors inhibits giant neurones in the
caudal pontine reticular nucleus.
AB - Giant neurones in the caudal pontine reticular nucleus (PnC) play a crucial role
in mediating the mammalian startle response. They receive input from cochlear,
trigeminal and vestibular nuclei and project directly to motoneurones.
Furthermore, they integrate modulatory input from different brain regions either
enhancing or inhibiting startle responses. One prominent startle modulation is
prepulse inhibition where a non-startling stimulus presented prior to the startle
stimulus inhibits a subsequent startle response. Several behavioural studies have
indicated that this inhibition is mediated by muscarinic receptors at the level
of the PnC. Here, we performed whole-cell patch-clamp recordings from PnC giant
neurones in acute rat brain slices in order to examine muscarinic inhibition. We
stimulated afferent trigeminal and auditory fibres and applied muscarinic
agonists and antagonists in order to investigate their effect on excitatory
postsynaptic current amplitudes, paired-pulse ratio and passive membrane
properties of PnC giant neurones. The cholinergic agonist carbachol and the
muscarinic agonist oxotremorine significantly reduced excitatory postsynaptic
current amplitudes and increased the paired-pulse ratio. Carbachol additionally
reduced the membrane resistance of postsynaptic PnC giant neurones. The subtype
specific antagonists AF-DX116 (M2 preferring) and tropicamide (M4 preferring)
antagonized the oxotremorine effect indicating that M4 and possibly M2 receptor
subtypes are involved in this inhibition. The G-protein-activated inward
rectifying potassium channel blocker tertiapin-Q had no effect on oxotremorine
induced inhibition of giant neurones. Our results show a mainly presynaptically
mediated strong inhibition of PnC giant neurones by activation of M4 and possibly
M2 receptors that presumably contribute to prepulse inhibition.
PMID- 17040475
TI - Striatum gray matter reduction in males with an overactive behavioral activation
system.
AB - Using optimized voxel-based morphometry, we studied the relationship between gray
matter volume in brain areas associated with reward and scores on a behavioral
activation system measure (the Sensitivity to Reward scale) in a sample of 50
male undergraduates. Voxel-based morphometry analysis revealed a negative
correlation between Sensitivity to Reward scores and gray matter volume in the
dorsal striatum and prefrontal cortex. Results indicate that a reduced volume in
the striatum might be associated with enhanced reward sensitivity and deficits in
inhibitory control.
PMID- 17040476
TI - Neurosteroid pregnenolone sulfate enhances glutamatergic synaptic transmission by
facilitating presynaptic calcium currents at the calyx of Held of immature rats.
AB - Pregnenolone sulfate (PREGS) is an endogenous neurosteroid widely released from
neurons in the brain, and is thought to play a memory-enhancing role. At
excitatory synapses PREGS facilitates transmitter release, but the underlying
mechanism is not known. We addressed this issue at the calyx of Held in rat
brainstem slices, where direct whole-cell recordings from giant nerve terminals
are feasible. PREGS potentiated nerve-evoked excitatory postsynaptic currents
(EPSCs) without affecting the amplitude of miniature EPSCs, suggesting that its
site of action is presynaptic. In whole-cell recordings from calyceal nerve
terminals, PREGS facilitated Ca2+ currents, by accelerating their activation
kinetics and shifting the half-activation voltage toward negative potentials.
PREGS had no effect on presynaptic K+ currents, resting conductance or action
potential waveforms. In simultaneous pre- and postsynaptic recordings, PREGS did
not change the relationship between presynaptic Ca2+ influx and EPSCs, suggesting
that exocytotic machinery downstream of Ca2+ influx is not involved in its
effect. PREGS facilitated Ba2+ currents recorded from nerve terminals and also
from HEK 293 cells expressed with recombinant N- or P/Q-type Ca2+ channels,
suggesting that PREGS-induced facilitation of voltage-gated Ca2+ channels (VGCCs)
is neither Ca2+ dependent nor VGCC-type specific. The PREGS-induced VGCC
facilitation was blocked by the PREGS scavenger (2-hydroxypropyl)-beta
cyclodextrin applied from outside, but not from inside, of nerve terminals. We
conclude that PREGS facilitates VGCCs in presynaptic terminals by acting from
outside, thereby enhancing transmitter release. We propose that PREGS may
directly modulate VGCCs acting on their extracellular domain.
PMID- 17040477
TI - Locomotor activity correlates with modifications of hippocampal mossy fibre
synaptic transmission.
AB - The hippocampus has long been implicated in memory formation. Although
accumulating evidence suggests involvement of the hippocampus in other brain
functions including locomotor regulation and emotional processes, cellular and
synaptic bases underlying these functions remain largely unknown. We here report
that environmental manipulations in mice unveiled the association of locomotor
activity with the hippocampal mossy fibre (MF) synaptic transmission.
Electrophysiological recordings of synaptic responses were made using hippocampal
slices prepared from mice whose behaviour had been analysed. Environmental
enrichment induced parallel decreases in open-field locomotor activity and MF
synaptic facilitation. Facilitation induced by paired-pulse stimulation at
relatively long intervals (>or=200 ms) was selectively reduced while the basal
synaptic efficacy and high-frequency transmission were unaffected. Social
isolation caused a change in behaviour in an elevated plus-maze, but neither the
open-field activity nor the MF synaptic transmission was significantly altered.
Effects of dopamine, a neurotransmitter essential for locomotor regulation, on
the MF synapse were also examined using these mice. Environmental manipulations
did not cause significant changes in potentiation of the MF synaptic transmission
induced by dopamine. However, analysis of behavioural and electrophysiological
results in individual subjects revealed that locomotor activity negatively
correlates with magnitude of the dopamine-induced potentiation. These results
suggest that the MF synapse plays important roles in the regulation of locomotor
activity. We propose that the MF synapse can serve as the synaptic model for
certain forms of locomotor regulation, with potential importance for
investigation of the pathophysiology of psychiatric diseases using animal models.
PMID- 17040478
TI - Injury-induced axonal sprouting in the hippocampus is initiated by activation of
trkB receptors.
AB - Penetrating head injuries are often accompanied by the delayed development of
post-traumatic epilepsy. Schaffer collateral transection leads to axonal
sprouting and hyperexcitability in area CA3 of hippocampal slice cultures. We
used this model to test the hypothesis that the injury-induced axonal sprouting
results from increased neurotrophin signaling via trkB receptors near the lesion.
Using rats and mice, we established that sprouting CA3 pyramidal cell axons are
labeled with an antibody to the growth-associated protein GAP-43. We observed two
to threefold increases in the level of brain-derived neurotrophic factor and
trkB protein in area CA3 by 24-48 h after Schaffer collateral transection,
preceding the onset of axonal sprouting. Finally, we demonstrated that injury
induced axonal sprouting of GAP-43-immunoreactive axons is impaired in
hippocampal slice cultures from mice expressing low levels of trkB receptors. We
conclude that injury-induced axonal sprouting is initiated by brain-derived
neurotrophic factor-trkB signaling and suggest that this process may be critical
for the genesis of post-traumatic epilepsy.
PMID- 17040479
TI - Mechanisms involved in modulation of trigeminal primary afferent activity in rats
with peripheral mononeuropathy.
AB - In order to clarify the mechanisms underlying the changes in primary afferent
neurons in trigeminal neuropathic pain, a chronic constriction nerve injury model
of the infraorbital nerve (ION-CCI) was developed in rats. Mechanical allodynia
was observed at 3 days after ION-CCI and lasted more than 14 days. Single-unit
activities were recorded from the ION of anesthetized rats. C-, Abeta- and Adelta
units were identified on the basis of their conduction velocity. Adelta-units
were frequently encountered at a later period after ION-CCI. The highest Adelta
spontaneous activity was recorded at 3 days after ION-CCI and progressively
decreased after that, but spontaneous activity was still higher at 14 days after
ION-CCI than that of naive rats. Mechanical-evoked responses of Adelta-units were
also highest at 3 days after ION-CCI and then gradually decreased. In
consideration of these data, patch-clamp recordings were performed on medium to
large size neurons of the dissociated trigeminal ganglion (TRG). Patch-clamp
recordings revealed that the IK (sustained) and IA (transient) in rats with ION
CCI were significantly smaller than those of naive rats, and correlated with an
increase in duration of repolarization phase and a decrease in duration of
depolarization phase, respectively. The hyperpolarization-activated current (Ih)
was significantly larger in TRG neurons of rats with ION-CCI as compared with
those of naive rats. The present results suggest that Ih, IK and IA in Adelta
afferent neurons in TRG are significantly involved in the changes in afferent
spontaneous activity and mechanically evoked activity that accompany mechanical
allodynia produced by trigeminal nerve injury.
PMID- 17040480
TI - Increased expression and activity of urokinase-type plasminogen activator during
epileptogenesis.
AB - Our recent large-scale molecular profiling study revealed a sevenfold
upregulation in the expression of urokinase-type plasminogen activator (uPA)
during epileptogenesis. uPA is a member of the plasminogen activation system,
which is a major contributor to the reorganization of neuronal circuits after
trauma. Here, we investigated the expression and activity of uPA in normal and
epileptogenic rat hippocampus to test a hypothesis that the expression of uPA is
altered in brain areas that undergo epilepsy-related circuitry reorganization.
Epileptogenesis was triggered by inducing status epilepticus (SE) with electrical
stimulation of the amygdala in rats. Continuous video-electroencephalogram
recordings were used to monitor the development of SE and the occurrence of
spontaneous seizures. Animals were killed at 1, 4 or 14 days after SE, and brains
were processed for immunohistochemistry or protein extraction. Confocal
microscopy analysis of double-immunolabelled preparations indicated that SE
triggered an increased expression of uPA in hippocampal astrocytes, neurons,
white matter and blood vessels. Zymography revealed that the expression of uPA
protein is associated with increased levels of enzymatically active uPA during
epileptogenesis. uPA expression and enzymatic activity peaked within 1-4 days
after SE, that is, before the occurrence of spontaneous seizures, and remained
elevated for at least 2 weeks. These data suggest that uPA is involved in the
reorganization of neuronal tissue during the epileptogenic process.
PMID- 17040481
TI - Brain-derived neurotrophic factor (BDNF) is required for the enhancement of
hippocampal neurogenesis following environmental enrichment.
AB - Neurogenesis continues to occur in the adult mammalian hippocampus and is
regulated by both genetic and environmental factors. It is known that exposure to
an enriched environment enhances the number of newly generated neurons in the
dentate gyrus. However, the mechanisms by which enriched housing produces these
effects are poorly understood. To test a role for neurotrophins, we used
heterozygous knockout mice for brain-derived neurotrophic factor (BDNF+/-) and
mice lacking neurotrophin-4 (NT-4-/-) together with their wild-type littermates.
Mice were either reared in standard laboratory conditions or placed in an
enriched environment for 8 weeks. Animals received injections of the mitotic
marker bromodeoxyuridine (BrdU) to label newborn cells. Enriched wild-type and
enriched NT-4-/- mice showed a two-fold increase in hippocampal neurogenesis as
assessed by stereological counting of BrdU-positive cells in the dentate gyrus
and double labelling for BrdU and the neuronal marker NeuN. Remarkably, this
enhancement of hippocampal neurogenesis was not seen in enriched BDNF+/- mice.
Failure to up-regulate BDNF accompanied the lack of a neurogenic response in
enriched BDNF heterozygous mice. We conclude that BDNF but not NT-4 is required
for the environmental induction of neurogenesis.
PMID- 17040482
TI - Biodiversity of Saccharomyces yeast strains from grape berries of wine-producing
areas using starter commercial yeasts.
AB - The use of commercial wine yeast strains as starters has grown extensively over
the past two decades. In this study, a large-scale sampling plan was devised over
a period of 3 years in three different vineyards in the south of France, to
evaluate autochthonous wine yeast biodiversity in vineyards around wineries where
active dry yeasts have been used as fermentation starters for more than 5 years.
Seventy-two spontaneous fermentations were completed from a total of 106 grape
samples, and 2160 colonies were isolated. Among these, 608 Saccharomyces strains
were identified and 104 different chromosomal patterns found. The large majority
of these (91) were found as unique patterns, indicating great biodiversity. There
were differences in biodiversity according to the vineyard and year, showing that
the biodiversity of Saccharomyces strains is influenced by climatic conditions
and specific factors associated with the vineyards, such as age and size. Strains
that were terroir yeast candidates were not found. The biodiversity of S.
cerevisiae strains after harvest was similar to that in the early campaign;
moreover, a temporal succession of S. cerevisiae strains is shown. This fact,
together with the differences in biodiversity levels verifies that other factors
were more important than commercial yeast utilization in the biodiversity of the
vineyard.
PMID- 17040483
TI - Study design, recruitment, and baseline characteristics: the Department of
Veterans Affairs Dental Diabetes Study.
AB - OBJECTIVES: We are conducting a clinical trial of the efficacy of periodontal
therapy in the improvement of glycaemic control in veterans with poorly
controlled diabetes. This report describes study design, recruitment and
randomization and compares baseline characteristics of the sample frame with
those randomized into study groups. METHODS: Veterans with poorly controlled
diabetes were randomized in two groups: immediate periodontal therapy ("early
treatment") or usual care followed by periodontal therapy ("deferred treatment").
Half of each group continued care for 12 months; the other half returned to their
usual care. We studied baseline patient characteristics, self-reported health
measures, and clinical examination data. We examined means for continuous
variables, frequencies for categorical variables and compared groups using t
tests and chi(2) tests (alpha=0.05 for both). RESULTS: The 193 randomized
participants were younger (58 years) and had slightly higher HbA1c (10.2%) than
the 2534 non-randomized participants (64 years, HbA1c =9.8%). The deferred
treatment group was more likely than the early treatment group to have a history
of stroke, transient ischaemic attacks, and less likely to be current or former
smokers. CONCLUSIONS: The mechanism for randomization was largely successful in
this study.
PMID- 17040485
TI - Endoplasmic reticulum and Golgi complex: Contributions to, and turnover by,
autophagy.
AB - The degradation of cytoplasmic contents, especially organelles [mitochondria,
peroxisomes, endoplasmic reticulum (ER), Golgi complex (GC)], cannot be
accomplished solely by the cytosolic degradation machinery, of which the most
prominent component is the proteasome. However, it is possible that such
organelles (or portions thereof) can be degraded by the cell's autophagic
machinery. In this manner, organelles can be either specifically or non
specifically targeted to the vacuole/lysosome for degradation. These processes
can be triggered in response to different environmental cues. Here, we focus on
two particular organelles, the ER and the GC, and their relationship with the
autophagic process. Firstly, we briefly consider how these two organelles
contribute to the synthesis and delivery of hydrolytic enzymes involved in
autophagy as well as how they may potentially contribute to their own degradation
by addressing the origin of the autophagic membrane. Secondly, we summarize the
evidence for the turnover of these two organelles by autophagic processes in
different organisms.
PMID- 17040484
TI - An efficacy and safety analysis of a chlorhexidine chewing gum in young
orthodontic patients.
AB - AIM: The objective of the present study was to investigate the impact of a
chlorhexidine (CHX) chewing gum in teenage orthodontic patients on plaque levels,
gingival bleeding tendency and tooth staining. MATERIALS AND METHODS: A
randomized-controlled, double-blind, parallel study was conducted on 31 teenagers
in fixed orthodontic therapy. Subjects of the CHX gum group were asked to
continue their oral hygiene procedures in conjunction with chewing two pieces of
a 5 mg CHX-containing chewing gum for 10 min. twice a day for 3 months. Subjects
of the placebo gum group received the same instructions; however, using a CHX
free chewing gum. Plaque levels, gingival bleeding on probing and tooth staining
were monitored at baseline and subsequently after 1-3 months. RESULTS: Plaque
levels significantly decreased from baseline at lingual/palatal sites in the
placebo gum group. In the CHX gum group, a similar, yet non-significant trend was
observed. At buccal sites, plaque levels remained unaffected in both groups.
Gingival bleeding tendency significantly decreased in both groups, predominantly
at lingual/palatal sites. There were no significant between-group differences in
any of the efficacy parameters at any time point. However, the increase in
staining was nearly five times higher in the CHX gum group. CONCLUSIONS: There
seems to be no indication for a CHX chewing gum in teenage orthodontic patients
when used as an adjunct to normal oral hygiene practices.
PMID- 17040486
TI - The prevalence of sexual dysfunction and potential risk factors that may impair
sexual function in Malaysian women.
AB - INTRODUCTION: Female sexual dysfunction (FSD) is a prevalent sexual health
problem that does not spare the women in Malaysia, a nation with a conservative
multiethnic society. AIM: To investigate the prevalence of FSD and the potential
risk factors that may impair sexual function among women at a primary care
setting in Malaysia. MAIN OUTCOME MEASURE: The prevalence, the risk factors, and
the main predictors for FSD were measured among these women. METHODS: A validated
Malay version of the Female Sexual Function Index was used to assess FSD. A total
of 230 married women aged 18-70 years participated in this study. The
sociodemographic and marital profiles of women who had FSD and those who did not
were compared; the risk factors for FSD were determined. RESULTS: The majority of
the respondents were younger than 50 years old, predominantly Malays, and had a
higher academic achievement. The prevalence of FSD in the primary care population
was 29.6%. The prevalence of women with lack of orgasms, low sexual arousal, lack
of lubrication, sexual dissatisfaction, and sexual pain were 59.1%, 60.9%, 50.4%,
52.2%, and 67.8%, respectively. CONCLUSION: The risk factors for FSD are older
age, Malays, married longer (more than 14 years), having less sexual intercourse
(less than 1-2 times a week), having more children, married to an older husband
(aged >42 years), and having a higher academic status. Lack of lubrication is
found to be the main predictor for FSD in this study. Is lack of lubrication a
cause or a complication of FSD? Prospective research is needed in the near
future.
PMID- 17040487
TI - Lung function, arterial saturation and oxygen uptake in elite cross country
skiers: influence of exercise mode.
AB - Arterial desaturation during exercise is common in endurance-trained athletes, a
phenomenon often more pronounced when the muscle mass engaged in the exercise is
large. With this background, the present study monitored seven international
level cross country skiers performing on a treadmill while running (RUN), double
poling (DP; upper body exercise) and diagonal skiing (DIA; arm and leg exercise).
Static and dynamic lung function tests were performed and oxygen uptake was
measured during submaximal and maximal exercise. Lung function variables
(including the diffusion capacity) were only 5-20% higher than reported in
sedentary men. Vital capacity was considerably lower than expected from the
skiers' maximal oxygen uptake (VO(2max)), but the maximal ventilation followed a
linear relationship with VO(2max). None or only a mild desaturation was observed
in DP, RUN and DIA. Blood lactate concentration was slightly higher in DIA than
in DP but not different from RUN. In DIA, VO(2max) was 6.23 +/- 0.47 L/min (mean
+/- SD), which was 3.8% and 13.9% higher than in RUN and DP, respectively, with
similar peak heart rates for the three exercise modes. No relationships were
present either between the degree of desaturation and pulmonary functions tests,
or with peak oxygen uptakes. The low blood lactate accumulation during the
exhaustive efforts contributed to the arterial oxygen saturation being mild in
spite of the very high oxygen uptake observed in these skiers.
PMID- 17040488
TI - Integration of omics data: how well does it work for bacteria?
AB - In the current omics era, innovative high-throughput technologies allow measuring
temporal and conditional changes at various cellular levels. Although individual
analysis of each of these omics data undoubtedly results into interesting
findings, it is only by integrating them that gaining a global insight into
cellular behaviour can be aimed at. A systems approach thus is predicated on data
integration. However, because of the complexity of biological systems and the
specificities of the data-generating technologies (noisiness, heterogeneity,
etc.), integrating omics data in an attempt to reconstruct signalling networks is
not trivial. Developing its methodologies constitutes a major research challenge.
Besides for their intrinsic value towards health care, environment and industry,
prokaryotes are ideal model systems to further develop these methods because of
their lower regulatory complexity compared with eukaryotes, and the ease with
which they can be manipulated. Several successful examples outlined in this
review already show the potential of the systems approach for both fundamental
and industrial applications, which would be time-consuming or impossible to
develop solely through traditional reductionist approaches.
PMID- 17040490
TI - Identification of the core transmembrane complex of the Legionella Dot/Icm type
IV secretion system.
AB - Type IV secretion systems (T4SS) are utilized by a wide range of Gram negative
bacteria to deliver protein and DNA substrates to recipient cells. The best
characterized T4SS are the type IVA systems, which exhibit extensive similarity
to the Agrobacterium VirB T4SS. In contrast, type IVB secretion systems share
almost no sequence homology to the type IVA systems, are composed of
approximately twice as many proteins, and remain largely uncharacterized. Type
IVB systems include the Dot/Icm systems found in the pathogens Legionella and
Coxiella and the conjugative apparatus of IncI plasmids. Here we report the first
extensive characterization of a type IVB system, the Legionella Dot/Icm secretion
apparatus. Based on biochemical and genetic analysis, we discerned the existence
of a critical five-protein subassembly that spans both bacterial membranes and
comprises the core of the secretion complex. This transmembrane connection is
mediated by protein dimer pairs consisting of two inner membrane proteins, DotF
and DotG, which are able to independently associate with DotH/DotC/DotD in the
outer membrane. The Legionella core subcomplex appears to be functionally
analogous to the Agrobacterium VirB7-10 subcomplex, suggesting a remarkable
conservation of the core subassembly in these evolutionarily distant type IV
secretion machines.
PMID- 17040491
TI - Different roles of P1 and P2 Saccharomyces cerevisiae ribosomal stalk proteins
revealed by cross-linking.
AB - The stalk is an essential domain of the large ribosomal subunit formed by a
complex of a set of very acidic proteins bound to a core rRNA binding component.
While in prokaryotes there is only one type acidic protein, L7/12, two protein
families are found in eukaryotes, phosphoproteins P1 and P2, which presumably
have different roles. To search for differences zero-length cross-linking by S-S
bridge formation was applied using Saccharomyces cerevisiae mutant P1 and P2
proteins carrying single cysteine residues at various positions. The results show
a more exposed location of the N-terminal domain of the P2 proteins, which in
contrast to P1, can be found as dimers when the Cys is introduced in this domain.
Similarly, the Cys containing C-terminal domain of mutant P2 proteins shows a
notable capacity to form cross-links with other proteins, which is considerably
lower in the P1 type. On the other hand, mutation at the conserved C-domain of
protein P0, the eukaryotic stalk rRNA binding component, results in removal of
about 14 terminal amino acids. Protein P2, but not P1, protects mutant P0 from
this truncation. These results support a eukaryotic stalk structure in which P1
proteins are internally located with their C-terminals having a restricted
reactivity while P2 proteins are more external and accessible to interact with
other cellular components.
PMID- 17040492
TI - The Hsp70 member, Ssa1, acts as a DNA-binding transcriptional co-activator of
laccase in Cryptococcus neoformans.
AB - Hsp70 proteins are a well-known class of chaperones that have also been described
to have roles in cellular regulation. Here, we show that a Cryptococcus
neoformans Hsp70 homologue Ssa1 acts as a DNA-binding transcriptional co
activator of the fungal virulence factor, laccase, via binding to a GC-rich
element within the 5'-UAS in response to glucose starvation, iron, copper,
calcium and temperature. In addition, Ssa1 forms a regulatory complex with heat
shock transcription factor and TATA-binding protein during laccase induction.
Furthermore, deletion of Ssa1 results in reduced laccase and attenuated virulence
using a mouse model. These results indicate that Hsp70 functions as a stress
related transcriptional co-activator required for fungal virulence.
PMID- 17040493
TI - Recent advances in chemical peeling in Japan.
AB - Chemical peeling is one of the dermatological treatments available for certain
cutaneous diseases and conditions or aesthetic improvement. This treatment
consists of the application of one or more chemical agents to the skin. Recently
in Japan, chemical peeling has been very popular for medical as well as aesthetic
treatment. Because the scientific background and an adequate approach have not
been completely established, medical and social problems have been reported. To
address these issues, the Japanese Dermatological Association has established
standard guidelines for chemical peeling, and the scientific background and
validity of chemical peeling has been assessed. In this review, a set of
guidelines for chemical peeling is introduced, and we will discuss several
clinical and histological studies including the effects of glycolic acid, and the
application of deer peeling to skin tumors in our department.
PMID- 17040494
TI - Vitamin D3 upregulated protein 1 (VDUP1) is a regulator for redox signaling and
stress-mediated diseases.
AB - Vitamin D(3) upregulated protein 1 (VDUP1) is a 46-kDa multifunctional protein,
initially isolated in HL-60 cells as a protein of which expression is upregulated
by vitamin D(3) administration. Subsequently, it was identified independently by
investigators from diverse scientific backgrounds as a thioredoxin binding
protein that negatively regulates the expression and the activity of thioredoxin,
and is thus involved in redox regulation. Further studies have revealed that
VDUP1 plays multiple roles in a wide range of cellular processes such as
proliferation or apoptosis. Recently, it has been reported that VDUP1 is also
involved in the immune system via positive regulation of natural killer
development. In addition, VDUP1 has been revealed to be associated with the fatty
acid utilization. In the present review, we discuss the novel aspects of VDUP1
function as well as the historical background of VDUP1. Future studies will
explore the diagnostic and therapeutic potential of modulating the function of
VDUP1 in vivo.
PMID- 17040495
TI - Collagen-poly glycolic acid hybrid matrix with basic fibroblast growth factor
accelerated angiogenesis and granulation tissue formation in diabetic mice.
AB - Because poor skin wound healing associated with diabetes is thought to be partly
a result from impaired angiogenesis, treatments that improve angiogenesis could
have important clinical applications. We herein report the effects of novel
developed material, collagen-poly glycolic acid fiber hybrid matrix, being used
together with basic fibroblast growth factor to promote wound healing of full
thickness skin defects on the back of type 2 diabetic Lepr(db) mice. Our data
indicates that this therapeutic approach markedly promotes angiogenesis and
granulation tissue formation in comparison with other conditions 14 days after
wounding.
PMID- 17040496
TI - Bidens pilosa suppresses interleukin-1beta-induced cyclooxygenase-2 expression
through the inhibition of mitogen activated protein kinases phosphorylation in
normal human dermal fibroblasts.
AB - Bidens pilosa (BP) Linn. var. radiata is a plant used in traditional folk
medicine. It is clinically effective in various diseases; the pathogenesis of
most of these involves cyclooxygenase (COX)-2. To investigate the mechanism on
which the clinical effectiveness of BP is based, we examined its effects on COX-2
expression and its major product, prostaglandin (PG)E(2), under conditions of
inflammation. We induced inflammation in normal human dermal fibroblasts with
interleukin (IL)-1beta and examined the effects of BP on COX-2 expression and
PGE(2) production using Western blotting and competitive enzyme immunoassay,
respectively. The functional involvements of mitogen activated protein kinases
(MAPK) ERK1/2, p38, and JNK in COX-2 expression were also examined by Western
blotting. IL-1beta-induced COX-2 expression was regulated by MAPK pathways,
especially by p38. BP inhibited the phosphorylation of MAPKs, COX-2 expression,
and subsequent PGE(2) production. The physiological activities and clinical
effectiveness of BP observed under diverse conditions may be partly attributable
to its ability to inhibit MAPK, mainly p38, activity, COX-2 expression, and
subsequent PGE(2) production.
PMID- 17040497
TI - Application of the Food and Drug Administration (FDA) bioequivalent guidance of
topical dermatological corticosteroid in yellow-skinned Japanese population:
validation study using a chromameter.
AB - The American Food and Drug Administration (FDA) bioequivalent guidance of topical
dermatological corticosteroids in 1995 (the Guidance) requires measurement of the
skin blanching response with a chromameter for evaluation of cutaneously applied
corticosteroid formulations. The Japanese government decided to apply the same
guidelines in 2003, despite there having been no reported trial for the yellow
skinned races. The purpose of this study was to obtain basic data of
corticosteroid-induced skin blanching response measured with a chromameter on
yellow-skinned races. Four studies were performed according to the Japanese
version of the Guidance for Industry using a chromameter on the forearms of
healthy Japanese volunteers. This involved: (i) a validation study of proper
duration of treatment exposure (dose duration); (ii) a comparison study of two
dermatological corticosteroid products that represented different potency
classes; (iii) inspection of reproducibility using right and left forearms; and
(iv) study of seasonal difference. We showed that: (i) the same medication can
give different values of ED(50) (the dose duration required to achieve 50% of the
fitted areas under the effect curves [AUEC](max) value) under different dose
durations; (ii) ED(50) do not always represent the potency of the corticosteroid;
(iii) the results of AUEC at maximum duration were similar, but AUEC at an
approximate ED(50) duration time varied widely; and (iv) the results of AUEC were
different according to season. In conclusion the dose duration relationships,
determination of the AUEC(max), and the ED(50) could be obtained on yellow
skinned races using the FDA method. However, negligible differences were found in
our study regarding dose duration, reproducibility and seasonal change.
PMID- 17040498
TI - Novel mutation (Asp158Val) in H1 domain of keratin 5 gene in a Japanese patient
with Kobner-type epidermolysis bullosa simplex.
AB - We describe a 19-year-old Japanese male with Kobner-type epidermolysis bullosa
simplex (EBS-KB) with a novel keratin gene mutation. The patient developed
blisters on the feet, palms, elbows and knees soon after birth. His father is
similarly affected with blistering, but his mother and younger brother are not
affected. Histological examination revealed that the primary separation in the
blister occurred within the basal cell layer. Sequence analysis demonstrated an A
to-T transition at the second position of codon 158 in the keratin 5 (K5) gene.
The amino acid at codon 158 was deduced to have changed from asparagine to
valine. We identified a novel mutation (Asp158Val) in the H1 domain of the K5
gene in this Japanese patient with EBS-KB. This is the first gene mutation report
of EBS-KB in the H1 domain of the K5 gene.
PMID- 17040499
TI - Androgenetic alopecia in adolescents: a report of 43 cases.
AB - Androgenetic alopecia (AGA) is the most common type of hair loss in adults, but
it also occurs in adolescents, though its prevalence among this younger
population is not well established. The purpose of this study was to evaluate the
clinical manifestations and endocrine status of adolescent patients with AGA in
Korea. This 5-year (January 2001-August 2005) clinical study involved 43
adolescent patients with AGA. Testosterone and dehydroepiandrosterone sulfate
(DHEA-S) laboratory studies were undertaken to investigate androgenic hormonal
effects. Hair loss severity was categorized using the Hamilton-Norwood and Ludwig
classifications. Gender ratio showed a male predominance (M : F, 35:8), and a
mean age at onset of 16.8 years. These adolescent patients showed milder symptoms
than adults, and a family history of alopecia was found in 72.1%, which is
greater than that reported in adults, which ranges 30.9-64.5%. Seborrheic
dermatitis (27.9%) was the condition most commonly associated with AGA among our
study subjects, followed in descending order by acne vulgaris and atopic
dermatitis. Serum levels of testosterone and DHEA-S were within normal limits,
except in one subject. Our study shows the clinical characteristics of AGA in
Korean adolescents.
PMID- 17040500
TI - Reverse sural artery flap for distal lower extremity defects.
AB - Traumatic and various dermatological conditions resulting in skin and
subcutaneous tissue loss on the lower limb cause a therapeutic challenge for the
dermatological surgeon, because this anatomical location lacks adequate skin
laxity and has limited local soft tissue, especially around the heel. In this
report, we present our experience with the reverse sural artery flap on seven
patients. The soft tissue defect was traumatic in two patients. We also treated
three diabetic patients. There were no immediate or late surgical complications
in four cases; flap and donor site healing was uneventful. The remaining three
cases were diabetic, and all presented with the following complications:
rejection of split skin graft at donor site, infection at the flap border and
superficial flap necrosis. The flap necrosis was concluded to be at least in part
due to the patient's noncompliance with postoperative measures. We conclude that
the reverse sural artery flap is a satisfactory alternative in the reconstruction
of lower limb defects, but we also feel that the importance of proper evaluation
prior to surgery in terms of vascular impairment and patient compliance should be
emphasized to ensure a successful surgical outcome.
PMID- 17040501
TI - Drug eruption caused by the nonionic contrast medium iohexol. "Recall-like
phenomenon" appearing on an area previously affected by herpes zoster.
AB - We report a case of "recall-like phenomenon" caused by nonionic contrast medium.
A 62-year-old woman suffering from postherpetic neuralgia developed erythematous
plaques 12 h after an intercostal nerve block under X-ray guidance using iohexol
(Omnipaque) as contrast medium. The erythematous plaques were preferentially
located in the sites where she had experienced herpes zoster 4 months previously.
The lesions cleared spontaneously leaving no pigmentation. Both patch testing and
intradermal testing with iohexol and ioversol were positive. We postulate that
local immunological changes in the skin, such as an increased number and/or
accelerated activity of Langerhans cells and mast cells in the herpes zoster
lesions, were responsible for this phenomenon. This "recall-like phenomenon",
occurring preferentially in skin previously affected by herpes zoster, could
facilitate understanding of the pathology of drug eruptions.
PMID- 17040502
TI - Generalized morphea and primary biliary cirrhosis coexisting in a male patient.
AB - We present further evidence that generalized morphea (GM) and primary biliary
cirrhosis (PBC) may be associated. As far as we know, only six cases with this
association have been previously reported in the published work, all of which
were observed in women. We describe the case of a 62-year-old man diagnosed with
M2-antibody-positive PBC who developed multiple generalized indurated plaques on
the trunk and extremities 3 years later. Clinical history, laboratory data and
histopathological examination were consistent with the diagnosis of GM. The
coexistence in a male of these two entities that predominantly affect females
reinforces the hypothesis that a pathogenic link exists between GM and PBC.
Consequently, PBC should be looked for in all patients with GM.
PMID- 17040503
TI - Juvenile-onset hypergammaglobulinemic purpura and fetal congenital heart block.
AB - Waldenstrom's hypergammaglobulinemic purpura (HGP) is a rare chronic disorder
characterized by recurrent purpura on the legs, a polyclonal increase in serum
gamma-globulin, an elevated erythrocyte sedimentation rate and a positive
rheumatoid factor. A 30-year-old primigravid woman with 14 years of HGP was found
to have fetal bradycardia at 25 weeks' gestation. Laboratory investigations
demonstrated positive anti-Ro/SSA and anti-La/SSB antibodies in the maternal
serum. Cesarean delivery was performed at 39 weeks, and a 2750-g female infant
was born with complete atrioventricular block. Fortunately, the neonatal period
has been uneventful without need for pace-making. Maternal HGP exacerbated just
after delivery, but resolved within 1 week without treatment. Physicians should
be aware of the possible presence of neonatal lupus-related anti-Ro/SSA and anti
La/SSB autoantibodies in patients with HGP. Screening for these autoantibodies is
important and could be used as a marker to identify and manage high-risk
pregnancies.
PMID- 17040504
TI - Granuloma caused by subcutaneous injection of leuprorelin acetate product: case
report and histopathological findings.
AB - Leuprorelin acetate is a luteinizing hormone-releasing hormone (LH-RH) analog,
which is used for chemical castration. Chemical castration treatment has an
especially important role for prostate cancer. To ensure ongoing chemical
castration, a novel sustained-action injection system using spherical
microcapsules has been developed. We report a patient who had granuloma caused by
administration of the 11.25 mg leuprorelin acetate product. Histological
examination revealed many giant cells with vacuoles. On the basis of reported
cases, these vacuoles are characteristic for the granuloma caused by leuprorelin
acetate product. The vacuoles in the granuloma are the same size as the
microcapsules, and their shape is almost spherical. We assume that the vacuoles
in the granuloma are actually the microcapsules. We expect that there will be
investigations regarding the procatarctic cause of granuloma formation.
PMID- 17040505
TI - Case of morphea occurring on a scar after laparoscopy.
PMID- 17040506
TI - Case of co-morbidity of alopecia areata and pityriasis lichenoides in a five year
old boy for two years.
PMID- 17040507
TI - Cicatricial pemphigoid with widespread bullous eruption.
PMID- 17040508
TI - Measuring and reporting what matters: a cornerstone for evidence-based health
care.
PMID- 17040509
TI - Evidence-based nursing practice: making progress and making a difference.
PMID- 17040510
TI - State-of-the-evidence reviews: advantages and challenges of including grey
literature.
AB - BACKGROUND: Increasingly, health policy decision-makers and professionals are
turning to research-based evidence to support decisions about policy and
practice. Systematic reviews are useful for gathering, summarizing, and
synthesizing published and unpublished research about clearly defined
interventions. State-of-the-evidence reviews are broader than traditional
systematic reviews and may include not only published and unpublished research,
but also published and unpublished non-research literature. Decisions about
whether to include this "grey literature" in a review are challenging and lead to
many questions about whether the advantages outweigh the challenges. AIMS: The
primary purpose of this article is to describe what constitutes grey literature,
and methods to locate it and assess its quality. The secondary purpose is to
discuss the core issues to consider when making decisions to include grey
literature in a state-of-the-evidence review. METHODS: A recent state-of-the
evidence review is used as an exemplar to present advantages and challenges
related to including grey literature in a review. RESULTS: Despite the
challenges, in the exemplar, inclusion of grey literature was useful to validate
the results of a research-based literature search. CONCLUSION: Decisions about
whether to include grey literature in a state-of-the-evidence review are complex.
A checklist to assist in decision-making was created as a tool to assist the
researcher in determining whether it is advantageous to include grey literature
in a review.
PMID- 17040511
TI - Constructing a new approach to developing evidence-based practice with nurses and
older people.
AB - PURPOSE: Providing evidence-based nursing care to older people is central to the
international development agenda. This paper is a report on the first 5 years
(2000-2005) of a participatory research project, the purpose of which was to
collaborate with practitioners and older people to develop approaches to promote
the attainment of evidence-based nursing care across Scotland. DESIGN: Many
theoretical influences shaped the design of this action research study including
realistic evaluation, participatory social learning theory, and descriptions of
communities of practice. Multiple methods of data collection were used during
four action cycles. The inaugural community of practice comprised 30 nurses, a
second group of 30 nurses joined midway, followed by a third group of 15 nurses,
and finally, an older person-carer community of 21 members was established.
FINDINGS: Project outputs included the construction of an internet-based,
practice-development college. A procedural model for developing and demonstrating
care guidance drawn from a diversity of evidence and reflective of an agreed set
of principles was piloted and endorsed by the national standard setting agency. A
preliminary version of a promising approach to practice development, "the
Caledonian Model," was delineated for future testing and refinement. CONCLUSION:
This work indicates the merits of using participatory research to find solutions
to the challenge of promoting evidence-based practice. Evaluation data suggest
that in combination, the approaches developed in this project empower nurses to
work with older people to champion developments even in seemingly unfavorable
conditions.
PMID- 17040512
TI - Development and testing of tools to assess physical restraint use.
AB - BACKGROUND: To implement best practice in restraint use, healthcare providers and
decision makers require current, accurate, and easily accessible information
about restraint practices in their setting. There is a need for a reliable and
valid instrument that is feasible for use in these settings to rapidly assess
physical restraint use. METHOD: Two instruments to assess physical restraint use
were developed and tested: an observation tool and a chart audit. The instruments
were tested in complex continuing care units and rehabilitation units at two
healthcare organizations. The restraint use observation tool was administered by
trained observers in a series of five observations over a 2-week period. Chart
audits were conducted for a sample of residents. Inter-rater agreement of the
observation tool and chart audit was assessed. Point prevalence estimates were
obtained for each site. The time required to use the observation tool and
complete chart audits as well as the comparability of findings from the two data
sources were described. FINDINGS: Restraint use observations were completed for
289 patients and chart audits were completed for 207 patients. Prevalence and
patterns of restraint use varied between sites and across time periods.
Observations took an average of 2.6 (Site A) and 0.6 (Site B) minutes per
patient. There was excellent inter-rater agreement for most items on the
observation tool with the exception of whether or not the patient was able to
release or loosen the restraint. There was significant concordance but as
expected, not complete agreement between paired estimates of prevalence using the
observational tool and the chart audit. CONCLUSION: The observation and chart
audit tools are feasible to use and reliably assess physical restraint use in
healthcare organizations. The patient's physical capacity to move independently,
the patient's waking status, and the restraint's restriction of mobility are
items that should be added to the observation tool. The tools are complementary
and should be used in tandem to capture the multifaceted complexity of restraint
use in health service organizations.
PMID- 17040514
TI - Re: Letter submission "Antiseptic obstetric cream for pelvic examination: where
is the evidence?".
PMID- 17040517
TI - Moral geographies of restraint in nursing homes.
PMID- 17040518
TI - A systematic review of the safety and effectiveness of restraint and seclusion as
interventions for the short-term management of violence in adult psychiatric
inpatient settings and emergency departments.
AB - AIMS: The aim of this review was to assess whether restraint and seclusion are
safe and effective interventions for the short-term management of
disturbed/violent behaviour. Staff and service user perspectives on the use of
these interventions were also considered. The review was undertaken as part of
the development process for a national guideline on the short-term management of
disturbed/violent behaviour in adult psychiatric inpatient settings and emergency
departments in the United Kingdom. METHOD: An exhaustive literature search was
undertaken. Systematic reviews, before and after studies, as well as qualitative
studies were included. Searches were run from 1985 to 2002. FINDINGS: Thirty-six
eligible studies were identified. However, none were randomised controlled
trials. Most of the included studies had many limitations, such as small sample
sizes, confounders not adequately accounted for, potential selection bias, poorly
reported results, and lack of clarity as to whether mechanical restraints were
used. This review must therefore be viewed as a mapping exercise, which
illustrates the range and quality of studies that have been undertaken in this
area to date. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Insufficient evidence is
available to determine whether seclusion and restraint are safe and/or effective
interventions for the short-term management of disturbed/violent behaviour in
adult psychiatric inpatient settings. These interventions should therefore be
used with caution and only as a last resort once other methods of calming a
situation and/or service user have failed.
PMID- 17040519
TI - Evidence base for practice: reduction of restraint and seclusion use during child
and adolescent psychiatric inpatient treatment.
AB - BACKGROUND: Restraint and seclusion of children has great potential for harm.
Since the mid-1980s, psychiatric inpatient personnel for children and adolescents
have put considerable energy in reducing the use of extreme measures of
aggression management. While the use of restraints is a particular problem in the
United States, aggression management and means of control in psychiatric settings
is an international issue. APPROACH: The core question of this review was: What
is the current state of the evidence supporting restraint reduction efforts with
children and adolescents? Studies were reviewed and critiqued that related to
programs of restraint reduction, restraint reduction methods, and aggression
management. Internationally, there seems to be more emphasis on reducing coercive
measures by understanding the context of their use. Thus, studies exploring staff
perceptions and decisions concerning coercive measures were also examined.
FINDINGS: The evidence supporting restraint reduction methods in the United
States comes mainly from case study reports of clinical sites' quality
improvement projects. Consequently, a collection of studies is accumulating that
supports a multi-strategy approach to restraint reduction. Limited evidence
exists for aggression management measures and training in de-escalation
techniques. Controversial aggression management techniques such as the use of pro
re nata medication and holding continue to be used with very little support for
their efficacy. RECOMMENDATIONS: Recommendations include taking a view of
restraint and seclusion as emergency measures to address dangerous aggression,
not interventions examined in controlled studies. As such it is suggested that
sites pool data on restraint use and reduction efforts to create a database for
benchmarking and studying variations among hospitals. Furthermore, attention
should also be given to developing additional means for addressing aggressive
behaviors.
PMID- 17040520
TI - Patient choice: an influencing factor on policy-related research to decrease
bedrail use as physical restraint.
AB - BACKGROUND: This paper shows patients' enactment of choice in mixed methods,
multidisciplinary study on the use of bedrails as restraints. APPROACH: Under the
pressure of the implementation of impending legislation, patients from a Canadian
elderly care rehabilitation unit were recruited to be part of this study and
assigned to either a study or control group. Study group patients were exposed to
a new facility policy on restraints in which bedrails were not to be used on a
patient's bed except under specified conditions. Patients in the control group
continued to have bedrails on a routine basis according to the facility's old
policy. Following group assignments, patients could choose to crossover to either
the control or study group based on their opinions about bedrails. FINDINGS:
After patients crossed over into either the study or control group, findings for
the new groups differed significantly. Participants in the rails-up group had
lower admission Functional Independence Measure scores (p = .001) and higher
admission Cumulative Illness Rating scores (p = .000) compared to those in the
rails-down group. CONCLUSIONS: Patients have specific concerns related to the use
of bedrails that might affect implementing bedrail minimization policies.
Additionally, the authors conclude that patients' input into research design may
increase patients' support of the protocol and help maintain study integrity.
PMID- 17040522
TI - Teaching EBP: the critical step of critically appraising the literature.
PMID- 17040523
TI - Resources for evidence-based practice.
PMID- 17040524
TI - The politics of evidence-based practice.
PMID- 17040525
TI - Contextual factors influencing research use in nursing.
AB - BACKGROUND: Contextual factors are perceived to be significant barriers to
research-utilisation-related activity, but little is known about how context
impacts on specific research-based decisions, or how the individual interacts
with the organisation in the requirement for research-based change. AIM: This
study describes the impact of contextual factors on the practical reasoning of
nurse specialists in the construction of policy for practice. METHODS: Three
groups of clinical nurse specialists were observed during a series of meetings
convened to construct evidence-based guidelines for nursing practice. Transcripts
of the meetings were analysed to identify and categorise the physical, social,
political, and economic influences on 31 nursing issues. FINDINGS: Multiple
contextual factors influenced each decision made, with decisions about nursing
practice bounded by setting and system considerations, relationships with others
in the care team, and resource constraints. Practitioners were involved in
weighing up alternative scenarios, contexts, and contingencies for each decision,
requiring strategies to adapt and reconstruct the nature of care, to influence
others, and to affect organisational decision-making processes. DISCUSSION: The
practical accomplishment of evidence-based practice required diverse skills:
translating between evidence and practice; mediating the values, preferences, and
working practices of multiple stakeholders; negotiating organisational complexity
and the management of boundaries; and coordinating inter-organisational and inter
agency working. Nurse specialists in this study had a significant role in
instigating, fuelling, and coordinating policy review, predominantly by
communication across professional and organisational boundaries.
IMPLICATIONS/CONCLUSIONS: Clinical specialists acting as organisational boundary
spanners require skills in the informal cultural work of organising,
facilitating, and maintaining links across professional, team, and organisational
boundaries. If their role in the negotiation of evidence-based practice patterns
across professional and organisational boundaries is to be successful, wider
skills than information management need to be recognised and their development
and enactment supported.
PMID- 17040526
TI - Barriers and facilitators influencing call center nurses' decision support for
callers facing values-sensitive decisions: a mixed methods study.
AB - BACKGROUND: Call center nurses triage symptoms and provide health information.
However, information alone is not adequate for people facing values-sensitive
health decisions. For these decisions, effective interventions are evidence-based
patient decision aids and in-person nurse coaching using a structured process.
Little is known about the quality of decision support provided by call center
nurses. AIMS: To identify the barriers and facilitators influencing the provision
of decision support by call center nurses to callers facing values-sensitive
health decisions at a Canadian province-wide health call center. METHODS: A mixed
qualitative and quantitative descriptive study from December 2003 to January 2004
using key informant interviews (n= 4), two focus groups (n= 7), a barriers
assessment survey (n= 57), and analysis of simulated patient calls (n= 38) were
carried out. Triangulation of these data was conducted using a conceptual content
analysis method. RESULTS: Participants indicated positive attitudes toward call
center nurses preparing callers facing values-sensitive decisions. Facilitators
included decision support resources, nurses' ability to recognize callers having
difficulty, and having a supportive organizational infrastructure. The most
frequently identified barriers were (a) limited usability of patient decision
aids via telephone; (b) lack of a structured process to guide nurses during these
types of calls; (c) nurses' inadequate knowledge, skills, and confidence in
providing values-sensitive decision support; (d) unclear program direction; (e)
organizational pressure to minimize call length; and (f) low public awareness of
the services. CONCLUSIONS AND IMPLICATIONS: Despite call center nurses having
positive attitudes, several modifiable barriers were interfering with nurses'
current approaches to supporting callers facing values-sensitive decisions.
Nurses wanted educational opportunities to further develop their decision support
knowledge and skills, and decision support resources that are easier to use via
telephone. As well, changes to organizational policies that address identified
barriers could further facilitate the provision of decision support.
PMID- 17040527
TI - Evaluating psychiatric nurses' awareness of evidence-based nursing publications.
AB - BACKGROUND: Research has shown that nurses lack skills to find and appraise
research literature, lack time and organisational support to utilise research,
and need user-friendly research material to implement evidence-based health care
in practice. In Sweden, the concept of evidence-based health care has been
introduced by The Swedish Council on Technology Assessment in Health Care (SBU),
a concept which the nursing profession quickly adopted. This study was initiated
synchronously with the publication of two reports on evidence-based nursing (EBN)
in psychiatric care. AIM: To investigate the dissemination and awareness of
literature on EBN among psychiatric nurses in Sweden, and more specifically
whether nurses were aware of the EBN reports. METHODS: A postal questionnaire was
used with a prospective pre-post design. A questionnaire was constructed and
distributed to the members in The National Association of Psychiatric Nurses at
two occasions--before publication of the two reports and 1 year post-publication.
The questionnaire was initially circulated to 2,294 nurses. The response rate for
the first distribution was 82% and for the second 72%. RESULTS: Although the
results demonstrate an increase in awareness concerning the concept of EBN and
access to literature between data collection, there were still many nurses who
reported no access to the literature. The reported use of literature in practice
was scarce; however, findings demonstrated an increase in opinion about the value
of using literature in practice. CONCLUSIONS: The findings of this study
demonstrate that the dissemination of literature in EBN, as well as EBN
literature in psychiatric care, still requires considerable development to assure
its use in practice. IMPLICATIONS: The diffusion and dissemination of evidence
based literature within nursing must be guided by a structured plan followed by
concrete examples of its implication(s) for practice.
PMID- 17040528
TI - Teaching EBP: getting to the gold: how to search for the best evidence.
PMID- 17040530
TI - Resources for evidence-based practice.
PMID- 17040531
TI - Implementing the evidence--how warm is the climate?
PMID- 17040532
TI - Outcomes and implementation strategies from the first U.S. Evidence-Based
Practice Leadership Summit.
PMID- 17040533
TI - Performing subcutaneous injections: a literature review.
AB - BACKGROUND: Persons using daily subcutaneous injections to administer medicine
perform them in different ways and thereby increase the risk of skin
complications related to the injection. It is often part of nurses' role to
administer medicine and educate the patient in injection technique. Course
literature in nursing education, commercial patient education pamphlets, and
instructional leaflets do not give consistent advice regarding subcutaneous
injection technique. AIM: The aim of this review was to identify the scientific
foundation for the technical performance of subcutaneous injections. The question
to be answered was: How should a subcutaneous injection be administered to
achieve the right dose in the right place with minimum complications? METHOD: The
review included a search in three databases, a screening process at abstract
level, followed by a quality assessment of included articles. The quality
assessment was done independently by two people and followed specific protocols.
RESULT: A total of 38 articles were assessed for quality and covered information
on dose, location, and complications of subcutaneous injection. The assessed
studies are heterogeneous in design and describe different aspects of the
subcutaneous injection technique. Therefore, the scientific foundation for
technical performance is weak. However, several studies indicate that the amount
of subcutaneous fat and appropriate needle length are of high importance for the
drug to reach the target tissue. CONCLUSION: More research regarding effective
subcutaneous injection technique needs to be done.
PMID- 17040534
TI - Developing postoperative pain management: utilising the promoting action on
research implementation in health services (PARIHS) framework.
AB - BACKGROUND: The development of acute pain services (APS), education programmes,
and protocols assumed an expectation that health care professionals would
integrate evidence into everyday practice. However, research evidence into pain
management would suggest that this is not the case. APPROACH: Through a review of
the literature, the authors aim to (1) explore the factors that have a
significant influence on getting evidence into practice (using the PARIHS model
as a guide) and (2) examine the relevance of these factors to postoperative pain
practices. FINDINGS: The need to assist clinicians with developing a greater
awareness of the competing and complex influences that surround pain management
practices is outlined. RECOMMENDATIONS: There is a necessity to adopt a
systematic, rigorous, and multidimensional approach to pain management issues,
utilising the PARIHS framework as a guide, to improve pain practices.
PMID- 17040535
TI - Space, place, and the evidence base: Part II--Rereading nursing environment
through geographical research.
AB - This, the second and final article in the short health geography series,
articulates how, moving beyond the models and assumptions associated with the
metaparadigm of Nursing Environment, as a focused subdisciplinary approach,
health geography might provide unique insights into nursing. A case study of a
fictional yet somewhat typical children's hospital is presented and demonstrates
some wide-ranging geographical issues and research questions (and hence potential
geographical data) pertaining to nursing and the allied health professions.
Indeed, this broad-brush approach is purposeful to make as many connections as
possible to readers with varied theoretical, methodological, empirical, and
practice expertise. In addition to the case study, to indicate further how
geographical inquiry might locate quite comfortably in nursing research, the
article also makes some initial and tentative connections between geography and
an established nursing framework for the uptake of research evidence for
practice. Although it is acknowledged that geographical inquiry should certainly
never have the first call on researching the relationships between nurses and
their environments, it is argued that its conceptual focus on space and place
provides dedicated and detailed attention and a sound basis for a reformed,
"spatialized" route to a more comprehensive understanding. Moreover, it is argued
that it also demonstrates great versatility in terms of the scales and the
subject matter with which it might engage. Some important issues certainly remain
with respect to what might be the correct form of engagement between geographical
and nursing research, but arguably, as a reformed disciplinary approach, health
geography has the potential to provide a wealth of focused evidence for nursing
practice.
PMID- 17040536
TI - Teaching EBP: asking searchable, answerable clinical questions.
PMID- 17040538
TI - Resources for evidence-based practice.
PMID- 17040540
TI - To synthesise or not synthesise? That is the question!
PMID- 17040541
TI - Quality improvement and evidence-based practice: As one or at odds in the effort
to promote better health care?
PMID- 17040542
TI - Space, place, and the evidence base: Part I--An introduction to health geography.
PMID- 17040543
TI - Evidence for smoking cessation: Implications for gender-specific strategies.
AB - BACKGROUND: Facilitating smoking cessation requires an evidence-based approach.
The Lienhard School of Nursing Institute for Healthy Aging in the United States,
whose focus is providing health information to aging baby boomers, developed an
interest in studying strategies for smoking cessation in women. APPROACH: Studies
were reviewed and critiqued related to the question: What is the relative
efficacy of first-line smoking cessation interventions for women versus men in
the 40- to 65-year-old age group? This article first discusses the procedure used
to construct an integrative framework for finding the evidence on smoking
cessation, including a literature search and refinement of the problem to be
studied, and then a summary of the evidence gathered on the selected variable
(gender) and interventions (counseling, pharmacotherapy, nicotine replacement
therapy). FINDINGS: Evidence was found that supports the general efficacy of
three first-line smoking cessation interventions: counseling, bupropion-sustained
release (BSR), and nicotine replacement therapy (NRT). What the evidence does not
show, however, is which of these interventions may be more effective for women
versus men in general or specifically in the 40- to 65-year-old age group.
RECOMMENDATIONS: Recommendations include the development of a clinical trial and
the inclusion from the outset of gender as a major variable in all future
intervention studies. IMPLICATIONS: Practice implications include the fact that
since effective treatments already exist for assisting clients to stop smoking,
all health-care providers should offer an intervention that has been found
effective to any client who expresses a desire to quit smoking. Further studies
of efficacy are needed to develop more focused implications.
PMID- 17040544
TI - Research and theory for Nursing and Midwifery: Rethinking the Nature of Evidence.
AB - BACKGROUND AND RATIONALE: The rise in the principles of evidence-based medicine
in the 1990s heralded a re-emerging orthodoxy in research methodologies. The view
of the randomised controlled trial (RCT) as a "gold standard" for evaluation of
medical interventions has extended recently to evaluation of organisational forms
and reforms and of change in complex systems-within health care and in other
human services. Relatively little attention has been given to the epistemological
assumptions underlying such a hierarchy of research evidence. AIMS AND METHODS:
Case studies from research in maternity care are used in this article to describe
problems and limitations encountered in using RCTs to evaluate some recent policy
driven and consumer-oriented developments. These are discussed in relation to
theory of knowledge and the epistemological assumptions, or paradigms,
underpinning health services research. The aim in this discussion is not to
advocate, or to reject, particular approaches to research but to advocate a more
open and critical engagement with questions about the nature of evidence.
FINDINGS AND DISCUSSION: Experimental approaches are of considerable value in
investigating deterministic and probabilistic cause and effect relationships, and
in testing often well-established but unevaluated technologies. However, little
attention has been paid to contextual and cultural factors in the effects of
interventions, in the culturally constructed nature of research questions
themselves, or of the data on which much research is based. More complex, and
less linear, approaches to methodology are needed to address these issues. A
simple hierarchical approach does not represent the complexity of evidence well
and should move toward a more cyclical view of knowledge development.
PMID- 17040545
TI - From workshop to work practice: An exploration of context and facilitation in the
development of evidence-based practice.
AB - BACKGROUND: This article examines the process of translating evidence into
practice using a facilitation model developed by the Western Australian Centre
for Evidence Based Nursing and Midwifery. AIMS: Using the conceptual framework
Promoting Action on Research Implementation in Health Services (PARIHS), the aims
of the study were (1) to explore the relative and combined importance of context
and facilitation in the successful implementation of a new evidence-based
clinical practice protocol and (2) to examine the establishment of more lasting
change to individuals and organizations that resulted in greater incorporation of
the principles of evidence-based practice (EBP). METHODS: A pre-workshop, semi
structured telephone survey with 16 nurse managers in six rural hospitals; a
summative evaluation immediately post-workshop with 54 participants; and follow
up, semi-structured interviews with 23 workshop participants. FINDINGS: The
contexts in each of the participating hospitals were very different; of the six
hospitals, only one had not implemented the new protocol. Five had reviewed their
practices and brought them in line with the protocol developed at the workshop.
The rate of adoption varied considerably from 2 weeks to months. The participants
reported being better informed about EBP in general and were positive about their
ability to improve their practice and search more efficiently for best practice
information. Underlying motivations for protocol development should be included
in the PARIHS framework. IMPLICATIONS FOR EDUCATION: Good facilitation appears to
be more influential than context in overcoming the barriers to the uptake of EBP.
PMID- 17040546
TI - Translating fall prevention best practices in the hospital setting: Reflecting on
McInnes and Askie's (2004) evidence review.
PMID- 17040547
TI - Teaching EBP: "Getting from zero to one." Moving from recognizing and admitting
uncertainties to asking searchable, answerable questions.
PMID- 17040549
TI - Getting evidence into practice: a contact sport.
PMID- 17040550
TI - A systematic review for effective management of central venous catheters and
catheter sites in acute care paediatric patients.
AB - BACKGROUND: Central venous catheters (CVCs) have provided many benefits in modern
day medical practice; however, they also put patients at risk of catheter-related
complications. Numerous studies have been carried out in relation to the
management of central venous catheters with conflicting results. While there were
several systematic reviews of central venous catheter-related issues, it is clear
that there was no systematic review of CVC-related studies specific to the
paediatric population in the acute care setting. OBJECTIVE: To present the best
available evidence for effective management of central venous catheters and
catheter sites in the prevention and/or reduction of catheter-related
complications in hospitalised paediatric patients. METHODS: A systematic review
was undertaken according to the approach of the Centre for Reviews and
Dissemination (CRD; http://www.york.ac.uk/inst/crd). DATA SOURCE: Literature was
identified by electronic searching of Cochrane Library, MEDLINE, CINAHL,
HealthSTAR, and CancerLit; checking references of all review articles; hand
searching of key relevant journals and conference proceedings; and contact with
expert informants, medical suppliers, and pharmaceutical companies.
INCLUSION/EXCLUSION CRITERIA: The review included randomised and non-randomised
controlled trials conducted with hospitalised paediatric patients. Studies that
included mixed adult and paediatric populations and mixed hospitalised and home
care settings were excluded. DATA EXTRACTION: Two independent reviewers extracted
data onto a standard data extraction form, with differences resolved by
discussion. QUALITY ASSESSMENT: The quality assessment of retrieved studies
included: study design, the degree to which systematic bias was avoided or
minimised, the degree to which the assessment was "blind," the degree to which
follow up was completed. DATA SYNTHESIS: Quantitative pooling of studies was not
feasible due to the diversity of interventions and outcome measures between
similar studies. A narrative account of the study characteristics and results was
therefore undertaken. RESULTS: Thirty-eight randomised and quasi-randomised
controlled trials were retrieved for critical appraisal. Of these, 32 were
excluded from the review because the studies did not meet the inclusion criteria
and some lacked reporting of appropriate data. Six studies met the criteria with
interventions such as antibiotic flushes, antiseptic skin preparations, and
dressing materials. CONCLUSION: Quality of reporting was generally lacking.
Statistical pooling of results was not possible due to diversity in the reporting
of outcomes. There was no evidence to make recommendations on the degree of
barrier precautions and the type of aseptic technique to be used at the time of
catheter insertion in the paediatric population to prevent catheter-related
infection. There was insufficient evidence to support the routine use of an
antibiotic flushing solution. There was a lack of randomised controlled trial
(RCT) evidence on the benefit of heparin flushes, the use of in-line filters, the
frequency of fluid administration set changes, or the type of dressing to use and
the frequency of dressing changes. There was some evidence to suggest that
chlorhexidine lotion is superior to povidone iodine as a cutaneous antiseptic at
the catheter insertion site. However, no recommendation can be made for the use
of chlorhexidine in neonates less than 2 weeks old or in premature infants. This
systematic review concluded that there is an urgent need for well-designed
randomised controlled trials with sufficient power to determine the effectiveness
of various interventions in relation to management of CVCs.
PMID- 17040552
TI - The concept of decisional control: building the base for evidence-based nursing
practice.
AB - PURPOSES: The purposes of this article are to add clarification to the meaning of
decisional control and provide a review of research related to the concept.
DEFINITIONS AND CHARACTERISTICS OF DECISIONAL CONTROL: A summary of the
definitions of decisional control is followed by a discussion of the
characteristics of the concept. The concept of decisional control includes the
ability or power to decide what will be one's involvement in health care
decisions. REVIEW OF RESEARCH: Studies on decisional control have tended to
center on inpatient, physician office, or clinic settings with a focus on the
diagnosis of cancer in which multiple medical treatment decisions arise. Most of
the research thus far has been performed in the United States and Canada related
to medical treatment. At this point, it is not entirely clear how patient
preferences for decisional control relate to health outcomes. MEASURING
DECISIONAL CONTROL: An overview of the tools available to measure decisional
control follows the review of the research. FUTURE DIRECTION: Future research
needs to focus on the identification of the differences in decisional control by
country, in differing cultural and ethnic groups within countries, and in various
geographical areas of countries. The relationship of patient characteristics
(e.g., age, gender, education, and income) to decisional control preferences is
not clearly identified. A large gap in the research relates to how nurses can
facilitate preferred decisional control to improve patient outcomes through
evidence-based nursing practice.
PMID- 17040553
TI - Sharing empirical knowledge to improve breastfeeding promotion and support:
description of a research dissemination project.
AB - BACKGROUND: Effective transfer of research findings to health care settings is a
shared priority among researchers, clinicians, and decision makers. A
multidisciplinary, multi-method investigation conducted in 2001 that explored
breastfeeding practices and support within a large immigrant community in
Montreal, Quebec, Canada, bore numerous implications for practice. Peer-reviewed
funding was subsequently granted to support dissemination of these findings to
relevant stakeholders. METHOD: Key steps in implementing this research
dissemination project included (1) identifying and attracting target audiences
from hospitals, community health settings, and government agencies; (2) tailoring
tools for communication of research findings to the various needs of audiences;
(3) designing interactive workshops to facilitate knowledge uptake; and (4)
integrating the project outcomes within a government-sponsored regional
breastfeeding committee for longer-term impact. FINDINGS: Despite organizational
challenges, more than 90 health care providers, decision makers, and
breastfeeding support volunteers participated in the project workshops. Through
feedback loops, the dissemination activities contributed new layers of
understanding to the original research findings. The activities also engaged
audience members to identify more effective breastfeeding support interventions
and led to the adoption of breastfeeding support priorities shared by hospital,
community, and government stakeholders. CONCLUSION: This dissemination project
provided unique opportunities for researchers and stakeholders to share in the
interpretation of research findings and to strategically plan for future
interventions to promote and support breastfeeding within ethnically diverse
communities. Further research dissemination work should continue to be
theoretically grounded, include systematic, long-term assessment of dissemination
outcomes, and be adequately financed throughout.
PMID- 17040554
TI - Clinical practice guideline for the assessment and prevention of falls in older
people.
PMID- 17040555
TI - Teaching EBP: a challenge for educators in the 21st century.
PMID- 17040558
TI - The DAMASK trial protocol: a pragmatic randomised trial to evaluate whether GPs
should have direct access to MRI for patients with suspected internal derangement
of the knee.
AB - BACKGROUND: Though new technologies like Magnetic Resonance Imaging (MRI) may be
accurate, they often diffuse into practice before thorough assessment of their
value in diagnosis and management, and of their effects on patient outcome and
costs. MRI of the knee is a common investigation despite concern that it is not
always appropriate. There is wide variation in general practitioners (GPs) access
to, and use of MRI, and in the associated costs. The objective of this study was
to resolve uncertainty whether GPs should refer patients with suspected internal
derangement of the knee for MRI or to an orthopaedic specialist in secondary
care. METHODS/DESIGN: The design consisted of a pragmatic multi-centre randomised
trial with two parallel groups and concomitant economic evaluation. Patients
presenting in general practice with suspected internal derangement of the knee
and for whom their GP was considering referral to an orthopaedic specialist in
secondary care were eligible for inclusion. Within practices, GPs or practice
nurses randomised eligible and consenting participants to the local radiology
department for an MRI examination, or for consultation with an orthopaedic
specialist. To ensure that the waiting time from GP consultation to orthopaedic
appointment was similar for both trial arms, GPs made a provisional referral to
orthopaedics when requesting the MRI examination. Thus we evaluated the more
appropriate sequence of events independent of variations in waiting times. Follow
up of participants was by postal questionnaires at six, twelve and 24 months
after randomisation. This was to ensure that the evaluation covered all events up
to and including arthroscopy. DISCUSSION: The DAMASK trial should make a major
contribution to the development of evidence-based partnerships between primary
and secondary care professionals and inform the debate when MRI should enter the
diagnostic pathway.
PMID- 17040559
TI - Pseudo current density maps of electrophysiological heart, nerve or brain
function and their physical basis.
AB - BACKGROUND: In recent years the visualization of biomagnetic measurement data by
so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became
popular. METHODS: The physical basis of these intuitive maps is clarified by
means of analytically solvable problems. RESULTS: Examples in
magnetocardiography, magnetoencephalography and magnetoneurography demonstrate
the usefulness of this method. CONCLUSION: Hardware realizations of the HC
transformation and some similar transformations are discussed which could
advantageously support cross-platform comparability of biomagnetic measurements.
PMID- 17040560
TI - Independent centromere formation in a capricious, gene-free domain of chromosome
13q21 in Old World monkeys and pigs.
AB - BACKGROUND: Evolutionary centromere repositioning and human analphoid
neocentromeres occurring in clinical cases are, very likely, two stages of the
same phenomenon whose properties still remain substantially obscure. Chromosome
13 is the chromosome with the highest number of neocentromeres. We reconstructed
the mammalian evolutionary history of this chromosome and characterized two human
neocentromeres at 13q21, in search of information that could improve our
understanding of the relationship between evolutionarily new centromeres,
inactivated centromeres, and clinical neocentromeres. RESULTS: Chromosome 13
evolution was studied, using FISH experiments, across several diverse
superordinal phylogenetic clades spanning >100 million years of evolution. The
analysis revealed exceptional conservation among primates (hominoids, Old World
monkeys, and New World monkeys), Carnivora (cat), Perissodactyla (horse), and
Cetartiodactyla (pig). In contrast, the centromeres in both Old World monkeys and
pig have apparently repositioned independently to a central location (13q21). We
compared these results to the positions of two human 13q21 neocentromeres using
chromatin immunoprecipitation and genomic microarrays. CONCLUSION: We show that a
gene-desert region at 13q21 of approximately 3.9 Mb in size possesses an inherent
potential to form evolutionarily new centromeres over, at least, approximately 95
million years of mammalian evolution. The striking absence of genes may represent
an important property, making the region tolerant to the extensive
pericentromeric reshuffling during subsequent evolution. Comparison of the
pericentromeric organization of chromosome 13 in four Old World monkey species
revealed many differences in sequence organization. The region contains clusters
of duplicons showing peculiar features.
PMID- 17040561
TI - Prediction of trans-antisense transcripts in Arabidopsis thaliana.
AB - BACKGROUND: Natural antisense transcripts (NATs) are coding or non-coding RNAs
with sequence complementarity to other transcripts (sense transcripts). These
RNAs could potentially regulate the expression of their sense partner(s) at
either the transcriptional or post-transcriptional level. Experimental and
computational methods have demonstrated the widespread occurrence of NATs in
eukaryotes. However, most previous studies only focused on cis-NATs with little
attention being paid to NATs that originate in trans. RESULTS: We have performed
a genome-wide screen of trans-NATs in Arabidopsis thaliana and identified 1,320
putative trans-NAT pairs. An RNA annealing program predicted that most trans-NATs
could form extended double-stranded RNA duplexes with their sense partners. Among
trans-NATs with available expression data, more than 85% were found in the same
tissue as their sense partners; of these, 67% were found in the same cell as
their sense partners at comparable expression levels. For about 60% of
Arabidopsis trans-NATs, orthologs of at least one transcript of the pair also had
trans-NAT partners in either Populus trichocarpa or Oryza sativa. The observation
that 430 transcripts had both putative cis- and trans-NATs implicates multiple
regulations by antisense transcripts. The potential roles of trans-NATs in
inducing post-transcriptional gene silencing and in regulating alternative
splicing were also examined. CONCLUSION: The Arabidopsis transcriptome contains a
fairly large number of trans-NATs, whose possible functions include silencing of
the corresponding sense transcripts or altering their splicing patterns. The
interlaced relationships observed in some cis- and trans-NAT pairs suggest that
antisense transcripts could be involved in complex regulatory networks in
eukaryotes.
PMID- 17040562
TI - Deep mtDNA divergences indicate cryptic species in a fig-pollinating wasp.
AB - BACKGROUND: Figs and fig-pollinating wasps are obligate mutualists that have
coevolved for ca. 90 million years. They have radiated together, but do not show
strict cospeciation. In particular, it is now clear that many fig species host
two wasp species, so there is more wasp speciation than fig speciation. However,
little is known about how fig wasps speciate. RESULTS: We studied variation in 71
fig-pollinating wasps from across the large geographic range of Ficus rubiginosa
in Australia. All wasps sampled belong to one morphological species
(Pleistodontes imperialis), but we found four deep mtDNA clades that differed
from each other by 9-17% nucleotides. As these genetic distances exceed those
normally found within species and overlap those (10-26%) found between
morphologically distinct Pleistodontes species, they strongly suggest cryptic fig
wasp species. mtDNA clade diversity declines from all four present in Northern
Queensland to just one in Sydney, near the southern range limit. However, at most
sites multiple clades coexist and can be found in the same tree or even the same
fig fruit and there is no evidence for parallel sub-division of the host fig
species. Both mtDNA data and sequences from two nuclear genes support the
monophyly of the "P. imperialis complex" relative to other Pleistodontes species,
suggesting that fig wasp divergence has occurred without any host plant shift.
Wasps in clade 3 were infected by a single strain (W1) of Wolbachia bacteria,
while those in other clades carried a double infection (W2+W3) of two other
strains. CONCLUSION: Our study indicates that cryptic fig-pollinating wasp
species have developed on a single host plant species, without the involvement of
host plant shifts, or parallel host plant divergence. Despite extensive evidence
for coevolution between figs and fig wasps, wasp speciation may not always be
linked strongly with fig speciation.
PMID- 17040563
TI - Oxidative stress is increased in critically ill patients according to antioxidant
vitamins intake, independent of severity: a cohort study.
AB - INTRODUCTION: Critically ill patients suffer from oxidative stress caused by
reactive oxygen species (ROS) and reactive nitrogen species (RNS). Although
ROS/RNS are constantly produced under normal circumstances, critical illness can
drastically increase their production. These patients have reduced plasma and
intracellular levels of antioxidants and free electron scavengers or cofactors,
and decreased activity of the enzymatic system involved in ROS detoxification.
The pro-oxidant/antioxidant balance is of functional relevance during critical
illness because it is involved in the pathogenesis of multiple organ failure. In
this study the objective was to evaluate the relation between oxidative stress in
critically ill patients and antioxidant vitamin intake and severity of illness.
METHODS: Spectrophotometry was used to measure in plasma the total antioxidant
capacity and levels of lipid peroxide, carbonyl group, total protein, bilirubin
and uric acid at two time points: at intensive care unit (ICU) admission and on
day seven. Daily diet records were kept and compliance with recommended dietary
allowance (RDA) of antioxidant vitamins (A, C and E) was assessed. RESULTS:
Between admission and day seven in the ICU, significant increases in lipid
peroxide and carbonyl group were associated with decreased antioxidant capacity
and greater deterioration in Sequential Organ Failure Assessment score. There was
significantly greater worsening in oxidative stress parameters in patients who
received antioxidant vitamins at below 66% of RDA than in those who received
antioxidant vitamins at above 66% of RDA. An antioxidant vitamin intake from 66%
to 100% of RDA reduced the risk for worsening oxidative stress by 94% (ods ratio
0.06, 95% confidence interval 0.010 to 0.39), regardless of change in severity of
illness (Sequential Organ Failure Assessment score). CONCLUSION: The critical
condition of patients admitted to the ICU is associated with worsening oxidative
stress. Intake of antioxidant vitamins below 66% of RDA and alteration in
endogenous levels of substances with antioxidant capacity are related to redox
imbalance in critical ill patients. Therefore, intake of antioxidant vitamins
should be carefully monitored so that it is as close as possible to RDA.
PMID- 17040564
TI - The reach of the genome signature in prokaryotes.
AB - BACKGROUND: With the increased availability of sequenced genomes there have been
several initiatives to infer evolutionary relationships by whole genome
characteristics. One of these studies suggested good congruence between genome
synteny, shared gene content, 16S ribosomal DNA identity, codon usage and the
genome signature in prokaryotes. Here we rigorously test the phylogenetic signal
of the genome signature, which consists of the genome-specific relative
frequencies of dinucleotides, on 334 sequenced prokaryotic genome sequences.
RESULTS: Intrageneric comparisons show that in general the genomic dissimilarity
scores are higher than in intraspecific comparisons, in accordance with the
suggested phylogenetic signal of the genome signature. Exceptions to this trend,
(Bartonella spp., Bordetella spp., Salmonella spp. and Yersinia spp.), which have
low average intrageneric genomic dissimilarity scores, suggest that members of
these genera might be considered the same species. On the other hand, high
genomic dissimilarity values for intraspecific analyses suggest that in some
cases (e.g. Prochlorococcus marinus, Pseudomonas fluorescens, Buchnera aphidicola
and Rhodopseudomonas palustris) different strains from the same species may
actually represent different species. Comparing 16S rDNA identity with genomic
dissimilarity values corroborates the previously suggested trend in phylogenetic
signal, albeit that the dissimilarity values only provide low resolution.
CONCLUSION: The genome signature has a distinct phylogenetic signal, independent
of individual genetic marker genes. A reliable phylogenetic clustering cannot be
based on dissimilarity values alone, as bootstrapping is not possible for this
parameter. It can however be used to support or refute a given phylogeny and
resulting taxonomy.
PMID- 17040565
TI - Reduction of anion reversal potential subverts the inhibitory control of firing
rate in spinal lamina I neurons: towards a biophysical basis for neuropathic
pain.
AB - BACKGROUND: Reduction of the transmembrane chloride gradient in spinal lamina I
neurons contributes to the cellular hyperexcitability producing allodynia and
hyperalgesia after peripheral nerve injury. The resultant decrease in anion
reversal potential (i.e. shift in Eanion to less negative potentials) reduces
glycine/GABAA receptor-mediated hyperpolarization, but the large increase in
membrane conductance caused by inhibitory input can nonetheless shunt concurrent
excitatory input. Without knowing the relative contribution of hyperpolarization
and shunting to inhibition's modulation of firing rate, it is difficult to
predict how much net disinhibition results from reduction of Eanion. We therefore
used a biophysically accurate lamina I neuron model to investigate quantitatively
how changes in Eanion affect firing rate modulation. RESULTS: Simulations reveal
that even a small reduction of Eanion compromises inhibitory control of firing
rate because reduction of Eanion not only decreases glycine/GABAA receptor
mediated hyperpolarization, but can also indirectly compromise the capacity of
shunting to reduce spiking. The latter effect occurs because shunting-mediated
modulation of firing rate depends on a competition between two biophysical
phenomena: shunting reduces depolarization, which translates into reduced
spiking, but shunting also shortens the membrane time constant, which translates
into faster membrane charging and increased spiking; the latter effect
predominates when average depolarization is suprathreshold. Disinhibition
therefore occurs as both hyperpolarization- and shunting-mediated modulation of
firing rate are subverted by reduction of Eanion. Small reductions may be
compensated for by increased glycine/GABAA receptor-mediated input, but the
system decompensates (i.e. compensation fails) as reduction of Eanion exceeds a
critical value. Hyperexcitability necessarily develops once disinhibition becomes
incompensable. Furthermore, compensation by increased glycine/GABAA receptor
mediated input introduces instability into the system, rendering it increasingly
prone to abrupt decompensation and even paradoxical excitation. CONCLUSION:
Reduction of Eanion dramatically compromises the inhibitory control of firing
rate and, if compensation fails, is likely to contribute to the allodynia and
hyperalgesia associated with neuropathic pain. These data help explain the
relative intractability of neuropathic pain and illustrate how it is important to
choose therapies not only based on disease mechanism, but based on quantitative
understanding of that mechanism.
PMID- 17040566
TI - Technology mediator: a new role for the reference librarian?
AB - The Arizona Health Sciences Library has collaborated with clinical faculty to
develop a federated search engine that is useful for meeting real-time clinical
information needs. This article proposes a technology mediation role for the
reference librarian that was inspired by the project, and describes the
collaborative model used for developing technology-mediated services for targeted
users.
PMID- 17040567
TI - Ethnomedicines used in Trinidad and Tobago for urinary problems and diabetes
mellitus.
AB - BACKGROUND: This paper is based on ethnobotanical interviews conducted from 1996
2000 in Trinidad and Tobago with thirty male and female respondents. METHODS: A
non-experimental validation was conducted on the plants used for urinary problems
and diabetes mellitus: This is a preliminary step to establish that the plants
used are safe or effective, to help direct clinical trials, and to inform
Caribbean physicians of the plants' known properties to avoid counter
prescribing. RESULTS: The following plants are used to treat diabetes: Antigonon
leptopus, Bidens alba, Bidens pilosa, Bixa orellana, Bontia daphnoides, Carica
papaya, Catharanthus roseus, Cocos nucifera, Gomphrena globosa, Laportea
aestuans, Momordica charantia, Morus alba, Phyllanthus urinaria and Spiranthes
acaulis. Apium graviolens is used as a heart tonic and for low blood pressure.
Bixa orellana, Bontia daphnoides, Cuscuta americana and Gomphrena globosa are
used for jaundice. The following plants are used for hypertension: Aloe vera,
Annona muricata, Artocarpus altilis, Bixa orellana, Bidens alba, Bidens pilosa,
Bonta daphnoides, Carica papaya, Cecropia peltata, Citrus paradisi, Cola nitida,
Crescentia cujete, Gomphrena globosa, Hibiscus sabdariffa, Kalanchoe pinnata,
Morus alba, Nopalea cochinellifera, Ocimum campechianum, Passiflora
quadrangularis, Persea americana and Tamarindus indicus. The plants used for
kidney problems are Theobroma cacao, Chamaesyce hirta, Flemingia strobilifera,
Peperomia rotundifolia, Petiveria alliacea, Nopalea cochinellifera, Apium
graveolens, Cynodon dactylon, Eleusine indica, Gomphrena globosa, Pityrogramma
calomelanos and Vetiveria zizanioides. Plants are also used for gall stones and
for cooling. CONCLUSION: Chamaesyce hirta, Cissus verticillata, Kalanchoe
pinnata, Peperomia spp., Portulaca oleraceae, Scoparia dulcis, and Zea mays have
sufficient evidence to support their traditional use for urinary problems,
"cooling" and high cholesterol. Eggplant extract as a hypocholesterolemic agent
has some support but needs more study. The plants used for hypertension, jaundice
and diabetes that may be safe and justify more formal evaluation are Annona
squamosa, Aloe vera, Apium graveolens, Bidens alba, Carica papaya, Catharanthus
roseus, Cecropia peltata, Citrus paradisi, Hibsicus sabdariffa, Momordica
charantia, Morus alba, Persea americana, Phyllanthus urinaria, Tamarindus indicus
and Tournefortia hirsutissima. Several of the plants are used for more than one
condition and further trials should take this into account.
PMID- 17040568
TI - Activin B can signal through both ALK4 and ALK7 in gonadotrope cells.
AB - BACKGROUND: Activins stimulate pituitary FSH synthesis via transcriptional
regulation of the FSHbeta subunit gene (Fshb). Like other members of the TGFbeta
superfamily, these ligands signal through complexes of type I and type II
receptor serine/threonine kinases. The type I receptors, or activin receptor-like
kinases (ALKs), propagate intracellular signals upon ligand binding and
phosphorylation by associated type II receptors. ALK4 is generally regarded as
the type I receptor for activins; however, recent data suggested that activin B
and AB might also signal through ALK7. Here, we examined a role for ALK7 in
activin B-regulated Fshb transcription. METHODS: We analyzed ALK7 mRNA expression
in immortalized gonadotrope cells, LbetaT2, and adult murine pituitary by RT-PCR.
We next transfected LbetaT2 cells with wild-type and kinase-deficient (Lys to
Arg, KR) forms of ALK4 and ALK7 and examined the effects of these receptors on
activin A and B stimulated Fshb promoter-reporter activity. Cells were also
transfected with constitutively active (Thr to Asp, TD) forms of the receptors
and their effects on endogenous Fshb mRNA levels and phosphorylation of
transfected Smad2/3 were measured by RT-PCR and Western blot, respectively.
Finally, we measured ALK4(TD) and ALK7(TD) stimulation of Fshb transcription when
endogenous Smad3 levels were depleted using short hairpin RNAs. RESULTS: ALK7
mRNA was expressed in LbetaT2 cells and pituitary gland. Transfection of ALK4
cDNA potentiated the effects of both activin A and activin B on Fshb promoter
reporter activity in LbetaT2 cells. In contrast, ALK7 transfection selectively
potentiated activin B's effects. Transfection of ALK4(KR) and ALK7(KR) partly
inhibited basal and activin B-stimulated reporter activity, whereas ALK4(TD) and
ALK7(TD) potently stimulated the Fshb promoter and endogenous mRNA levels.
Transfection of both ALK4(TD) and ALK7(TD) stimulated Smad2/3 phosphorylation,
and the effects of both receptors on Fshb promoter activity were inhibited by
depletion of endogenous Smad3 protein levels. CONCLUSION: These data suggest that
immortalized gonadotropes express ALK7 and that activin B can signal through this
receptor to stimulate Fshb transcription. The relative roles of endogenous ALK4
and ALK7 receptors in mediating activin B's effects in these cells have yet to be
determined.
PMID- 17040569
TI - Living with primary ciliary dyskinesia: a prospective qualitative study of
knowledge sharing, symptom concealment, embarrassment, mistrust, and stigma.
AB - BACKGROUND: Primary ciliary dyskinesia (PCD) is a chronic respiratory disease for
which there is little psycho-social research and no qualitative studies of
individuals living with the condition. A questionnaire-based survey in 2003 found
evidence of stigmatisation in some individuals with PCD. Although the
questionnaire had face and construct validity, stigmatisation was not cross
validated against interviews. The present study had the twin aims of carrying out
a qualitative study of the adult patients living with PCD, and using a structured
design to validate the questionnaire measure of stigma. METHODS: Interviews were
carried out with six pairs of individuals with PCD, matched for sex, situs, and
age, one with a high stigma score in 2003 and the other with a low stigma score.
Depth-qualitative interviews were conducted by one author to explore themes
surrounding the psycho-social impact of PCD using a grounded theory analysis. The
interviewer was blind to the stigma scores of participants, and after the
qualitative analysis was completed, the interviewer made an assessment of which
member of each pair seemed the more stigmatised, after which the code was broken.
RESULTS: Interviews revealed a number of themes, including other people's
knowledge of PCD, the sharing of knowledge about PCD, the concealment of symptoms
of PCD, embarrassment at symptoms, changes of behaviour in response to PCD,
mistrust of medical care, in particular in relation to problems in diagnosis, a
mistrust of general practitioners who were seen as poorly informed, and the
importance of expert care at tertiary referral centres. Although stigmatisation
as such was rarely mentioned directly by respondents, when the interviewer's
judgement on level of stigmatisation was correlated with stigma scores from 2003,
it was found that the more stigmatised member had been correctly identified in
all six pairs (p = .016). CONCLUSION: Our results suggest that some people with
PCD feel isolated through mistrust in medicine, and lack of knowledge surrounding
PCD. Many responses to PCD can be explained in terms of stigmatisation, and in
particular felt stigma. The correlation between questionnaire used several years
previously, and the interviewer's judgements of stigmatisation suggest that the
stigma questionnaire had both predictive validity and long-term stability. As in
other chronic conditions, stigmatisation occurs only in some individuals with
PCD, and the present study explores the basis of stigmatisation, and validate the
questionnaire as a measure of difference in stigma.
PMID- 17040570
TI - Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13,
12p13, 17q12, and 20q13 amplifications in breast cancers.
AB - BACKGROUND: Oncogene amplification and overexpression occur in tumor cells.
Amplification status may provide diagnostic and prognostic information and may
lead to new treatment strategies. Chromosomal regions 8p12, 8q24, 11q13, 17q12
and 20q13 are recurrently amplified in breast cancers. METHODS: To assess the
frequencies and clinical impact of amplifications, we analyzed 547 invasive
breast tumors organized in a tissue microarray (TMA) by fluorescence in situ
hybridization (FISH) and calculated correlations with histoclinical features and
prognosis. BAC probes were designed for: (i) two 8p12 subregions centered on
RAB11FIP1 and FGFR1 loci, respectively; (ii) 11q13 region centered on CCND1;
(iii) 12p13 region spanning NOL1; and (iv) three 20q13 subregions centered on
MYBL2, ZNF217 and AURKA, respectively. Regions 8q24 and 17q12 were analyzed with
MYC and ERBB2 commercial probes, respectively. RESULTS: We observed amplification
of 8p12 (amplified at RAB11FIP1 and/or FGFR1) in 22.8%, 8q24 in 6.1%, 11q13 in
19.6%, 12p13 in 4.1%, 17q12 in 9.9%, 20q13Z (amplified at ZNF217 only) in 9.9%,
and 20q13Co (co-amplification of two or three 20q13 loci) in 8.5% of cases. The
8q24, 12p13, and 17q12 amplifications were correlated with high grade. The most
frequent single amplifications were 8p12 (9.8%), 8q24 (3.3%) and 12p13 (3.3%),
20q13Z and 20q13Co (1.6%) regions. The 17q12 and 11q13 regions were never found
amplified alone. The most frequent co-amplification was 8p12/11q13.
Amplifications of 8p12 and 17q12 were associated with poor outcome. Amplification
of 12p13 was associated with basal molecular subtype. CONCLUSION: Our results
establish the frequencies, prognostic impacts and subtype associations of various
amplifications and co-amplifications in breast cancers.
PMID- 17040572
TI - Antithrombin significantly influences platelet adhesion onto immobilized
fibrinogen in an in-vitro system simulating low flow.
AB - BACKGROUND: Adhesion of platelets onto immobilized fibrinogen is of importance in
initiation and development of thrombosis. According to a recent increase in
evidence of a multiple biological property of antithrombin, we evaluated the
influence of antithrombin on platelet adhesion onto immobilized fibrinogen using
an in-vitro flow system. METHODS: Platelets in anticoagulated whole blood (29
healthy blood donors) were labelled with fluorescence dye and perfused through a
rectangular flow chamber (shear rates of 13 s-1 to 1500 s-1). Platelet adhesion
onto fibrinogen-coated slips was assessed using a fluorescence laser-scan
microscope and compared to the plasma antithrombin activity. Additionally the
effect of supraphysiological AT supplementation on platelets adhesion rate was
evaluated. RESULTS: Within a first minute of perfusion, an inverse correlation
between platelet adhesion and plasma antithrombin were observed at 13 s-1 and 50
s-1 (r = -0.48 and r = -0.7, p < 0.05, respectively). Significant differences in
platelet adhesion related to low (92 +/- 3.3%) and high (117 +/- 4.1%)
antithrombin activity (1786 +/- 516 U vs. 823 +/- 331 U, p < 0.05) at low flow
rate (13 s-1, within first minute) have been found. An in-vitro supplementation
of whole blood with antithrombin increased the antithrombin activity up to 280%
and platelet adhesion rate reached about 65% related to the adhesion rate in a
non-supplemented blood (1.25 +/- 0.17 vs. 1.95 +/- 0.4 p = 0.008, respectively).
CONCLUSION: It appears that antithrombin in a low flow system suppresses platelet
adhesion onto immobilized fibrinogen independently from its antithrombin
activity. A supraphysiological substitution of blood with antithrombin
significantly reduces platelet adhesion rate. This inhibitory effect might be of
clinical relevance.
PMID- 17040571
TI - Health-related quality of life of Canadian children and youth prenatally exposed
to alcohol.
AB - BACKGROUND: In Canada, the incidence of Fetal Alcohol Spectrum Disorder (FASD)
has been estimated to be 1 in 100 live births. Caused by prenatal exposure to
alcohol, FASD is the leading cause of neuro-developmental disabilities among
Canadian children, and youth. OBJECTIVE: To measure the health-related quality of
life (HRQL) of Canadian children and youth diagnosed with FASD. METHODS: A
prospective cross-sectional study design was used. One-hundred and twenty-six
(126) children and youth diagnosed with FASD, aged 8 to 21 years, living in urban
and rural communities throughout Canada participated in the study. Participants
completed the Health Utilities Index Mark 3 (HUI3). HUI3 measures eight health
attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition,
and pain. Utilities were used to measure a single cardinal value between 0 and
1.0 (0 = all-worst health state; 1 = perfect health) to reflect the global HRQL
for that child. Mean HRQL scores and range of scores of children and youth with
FASD were calculated. A one-sample t-test was used to compare mean HRQL scores of
children and youth with FASD to those from the Canadian population. RESULTS: Mean
HRQL score of children and youth with FASD was 0.47 (95% CI: 0.42 to 0.52) as
compared to a mean score of 0.93 (95% CI: 0.92 to 0.94) in those from the general
Canadian population (p < 0.001). Children demonstrated moderate to severe
dysfunction on the single-attributes of cognition and emotion. CONCLUSION:
Children and youth with FASD have significantly lower HRQL than children and
youth from the general Canadian population. This finding has significant
implications for practice, policy development, and research.
PMID- 17040573
TI - Rural-urban differentials of premature mortality burden in south-west China.
AB - BACKGROUND: Yunnan province is located in south western China and is one of the
poorest provinces of the country. This study examines the premature mortality
burden from common causes of deaths among an urban region, suburban region and
rural region of Kunming, the capital of Yunnan. METHODS: Years of life lost (YLL)
rate per 1,000 and mortality rate per 100,000 were calculated from medical death
certificates in 2003 and broken down by cause of death, age and gender among
urban, suburban and rural regions. YLL was calculated without age-weighting and
discounting rate. Rates were age-adjusted to the combined population of three
regions. However, 3% discounting rate and a standard age-weighting function were
included in the sensitivity analysis. RESULTS: Non-communicable diseases
contributed the most YLL in all three regions. The rural region had about 50%
higher premature mortality burden compared to the other two regions. YLL from
infectious diseases and perinatal problems was still a major problem in the rural
region. Among non-communicable diseases, YLL from stroke was the highest in the
urban/suburban regions; COPD followed as the second and was the highest in the
rural region. Mortality burden from injuries was however higher in the rural
region than the other two regions, especially for men. Self-inflicted injuries
were between 2-8 times more serious among women. The use of either mortality rate
or YLL gives a similar conclusion regarding the order of priority. Reanalysis
with age-weighting and 3% discounting rate gave similar results. CONCLUSION:
Urban south western China has already engaged in epidemiological pattern of
developed countries. The rural region is additionally burdened by diseases of
poverty and injury on top of the non-communicable diseases.
PMID- 17040574
TI - Passive immunoprophylaxis and therapy with humanized monoclonal antibody specific
for influenza A H5 hemagglutinin in mice.
AB - BACKGROUND: Highly pathogenic avian H5N1 influenza virus is a major public health
concern. Given the lack of effective vaccine and recent evidence of antiviral
drug resistance in some isolates, alternative strategies for containment of a
possible future pandemic are needed. Humanized monoclonal antibodies (mAbs) that
neutralize H5N1 virus could be used as prophylaxis and treatment to aid in the
containment of such a pandemic. METHODS: Neutralizing mAbs against H5
hemagglutinin were humanized and introduced into C57BL/6 mice (1, 5, or 10 mg/kg
bodyweight) one day prior to-, one day post- and three days post-lethal challenge
with H5N1 A/Vietnam/1203/04 virus. Efficacy was determined by observation of
weight loss as well as survival. RESULTS: Two mAbs neutralizing for antigenically
variant H5N1 viruses, A/Vietnam/1203/04 and A/Hong Kong/213/03 were identified
and humanized without loss of specificity. Both antibodies exhibited prophylactic
efficacy in mice, however, VN04-2-huG1 performed better requiring only 1 mg/kg
bodyweight for complete protection. When used to treat infection VN04-2-huG1 was
also completely protective, even when introduced three days post infection,
although higher dose of antibody was required. CONCLUSION: Prophylaxis and
treatment using neutralizing humanized mAbs is efficacious against lethal
challenge with A/Vietnam/1203/04, providing proof of principle for the use of
passive antibody therapy as a containment option in the event of pandemic
influenza.
PMID- 17040575
TI - Analysis of role-play in medical communication training using a theatrical device
the fourth wall.
AB - BACKGROUND: Communication training is a central part of medical education. The
aim of this article is to explore the positions and didactic functions of the
fourth wall in medical communication training, using a role-play model basically
similar to a theatrical performance. METHOD: The empirical data stem from a
communication training model demonstrated at an international workshop for
medical teachers and course organizers. The model involves an actress playing a
patient, students alternating in the role of the doctor, and a teacher who
moderates. The workshop was videotaped and analyzed qualitatively. RESULTS: The
analysis of the empirical material revealed three main locations of the fourth
wall as it moved and changed qualities during the learning session: 1) A
traditional theatre location, where the wall was transparent for the audience,
but opaque for the participants in the fiction. 2) A "timeout/reflection"
location, where the wall was doubly opaque, for the patient on the one side and
the moderator, the doctor and the audience on the other side and 3) an
"interviewing the character" location where the wall enclosed everybody in the
room. All three locations may contribute to the learning process. CONCLUSION: The
theatrical concept 'the fourth wall' may present an additional tool for new
understanding of fiction based communication training. Increased understanding of
such an activity may help medical teachers/course organizers in planning and
evaluating communication training courses.
PMID- 17040576
TI - Adenocarcinoma of the caecum metastatic to the bladder: an unusual cause of
haematuria.
AB - BACKGROUND: Primary malignancies of colorectal origin can metastasise to the
bladder. Reports are however extremely rare, particularly from the caecum. CASE
REPORT: The report describes the case of a 45-year old male with Duke's B caecal
carcinoma treated with a laparoscopically-assisted right hemicolectomy and
adjuvant 5-Fluorouracil chemotherapy. Subsequently, a metastatic lesion to the
bladder was demonstrated and successfully excised by partial cystectomy.
CONCLUSION: In order that optimal therapeutic options can be determined, it is
important for clinicians to distinguish between primary disease of the bladder
and other causes of haematuria. Various immunohistochemical techniques attempt to
differentiate primary adenocarcinoma of the bladder from secondary colorectal
adenocarcinoma. Suspicion of metastatic disease must be raised when
histologically unusual bladder tumours are identified.
PMID- 17040577
TI - Circulating immune complexes and trace elements (Copper, Iron and Selenium) as
markers in oral precancer and cancer : a randomised, controlled clinical trial.
AB - AIM: To evaluate the levels of circulating immune complexes, trace elements
(copper, iron and selenium) in serum of patients with oral submucous fibrosis
(OSMF), oral leukoplakia (L), and oral squamous cell carcinoma (SCC), analyze the
alteration and identify the best predictors amongst these parameters for disease
occurrence and progression. METHODS: Circulating immune complexes (CIC) were
estimated using 37.5% Polyethylene Glycol 6000(PEG) serum precipitation. Serum
estimation of copper (Cu), Iron (Fe) and selenium (Se) was done using the Oxalyl
Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse
Cathodic Stripping Voltametry respectively. RESULTS: The data analysis revealed
increased circulating immune complex levels in the precancer and cancer patients.
Serum copper levels showed gradual increase from precancer to cancer patients.
However, serum iron levels were decreased significantly in the cancer group.
Selenium levels showed marked decrease in the cancer group. Among CIC, serum,
copper, iron and selenium the best predictors for the occurrence of lesions were
age, serum iron, CIC, serum selenium in the decreasing order. CONCLUSION: The
present study shows that these immunological and biological markers may be
associated with the pathogenesis of oral premalignant and malignant lesions and
their progressions. Concerted efforts would, therefore, help in early detection,
management, and monitoring the efficacy of treatment.
PMID- 17040578
TI - Molecular basis of inherited skin-blistering disorders, and therapeutic
implications.
AB - Epidermolysis bullosa (EB) and associated skin-fragility syndromes are a group of
inherited skin diseases characterised by trauma-induced blistering of the skin
and mucous membranes. Mutations in at least 14 distinct genes encoding molecular
components of the epidermis or the dermal-epidermal junction (DEJ) can cause
blistering skin diseases that differ by clinical presentation and severity of the
symptoms. Despite great advances in discerning the genetic basis of this group of
diseases, the molecular pathways leading to symptoms are not yet fully
understood. Unravelling these pathways by molecular analysis of the structure and
in vitro assessment of functional properties of the human proteins involved,
combined with genetic models in lower organisms, should pave the way for specific
cures for inherited skin fragility.
PMID- 17040579
TI - Tornwaldt's cyst formation after concurrent chemoradiotherapy for nasopharyngeal
carcinoma.
AB - The complications of concurrent chemoradiotherapy for nasopharyngeal carcinoma
include dryness of mouth, sensorineural hearing loss, dental caries, trismus,
pituitary dysfunction, myelitis, paralysis of cranial nerves IX-XII, massive neck
fibrosis and pharyngeal wall necrosis. Tornwaldt's cyst formation after
concurrent chemoradiotherapy for nasopharyngeal carcinoma has not been reported
previously in the world literature. Tornwaldt's cyst, a persistent pharyngeal
bursa, is found in about 3 per cent of the adult population, although the
majority of these are asymptomatic. We describe the previously unreported
complication of Tornwaldt's cyst formation after concurrent chemoradiotherapy for
nasopharyngeal carcinoma.
PMID- 17040580
TI - Long-term outcomes of laser-assisted uvulopalatoplasty in 168 patients with
snoring.
AB - Laser-assisted uvulopalatoplasty (LAUP) is an established treatment for snoring.
Our institution has been using a modification of the Kamami technique since 1995.
Between January 1995 and December 2001, 469 patients underwent LAUP for snoring.
A telephone survey of these patients and their partners was conducted
retrospectively. One hundred and sixty-eight patients and their partners were
interviewed and the findings analysed.Of the 168 patients, 122 had LAUP alone, 42
had LAUP and tonsillectomy and four had LAUP and septoplasty. The median follow
up time was 59 months (range 19 to 98 months).Seventy-four per cent reported
improvement at six weeks, 69 per cent reported improvement at nine months and 55
per cent reported improvement at the time of interview. To assess the degree of
improvement, patients and their partners were asked to grade any improvement in
percentage terms. The mean subjective improvement scores were 57 per cent at six
weeks (95 per cent confidence interval (CI) 50-64 per cent), 45 per cent at nine
months (95 per cent CI 38-59 per cent) and 30 per cent at the time of interview
(95 per cent CI 23-35 per cent). Patients who reported weight gain since surgery
did not have a poorer outcome than those who reported no weight change or weight
loss. Neither did weight loss predict a better outcome. The procedure was
generally well tolerated, with only 30 patients (18 per cent) reporting
complications (mainly minor). The benefits of LAUP wane with time and the results
are best in the first 12 months following surgery. Our study suggests that 55 per
cent of patients selected after sleep studies and sleep nasendoscopy will enjoy
long-term benefit.
PMID- 17040581
TI - Angina masquerading as sinusitis.
AB - Facial pain of cardiac origin is rare. There are several references in the world
literature to angina referred to the teeth and the mandible. This report
describes a patient with facial pain which was thought to be of sinus origin and
which was relieved by coronary stenting.
PMID- 17040582
TI - Otolaryngological requirements for recreational self-contained underwater
breathing apparatus (SCUBA) diving.
AB - Recreational self-contained underwater breathing apparatus (SCUBA) diving
continues to grow in popularity. Medical requirements to be 'fit to dive' vary
throughout the world, from self-certification to a full medical examination prior
to training. This review discusses the relative merits of the most commonly used
guidelines for recreational SCUBA diving, with reference to common diving-related
otorhinolaryngological conditions. Areas of controversy, such as fitness to dive
after rhinological and otological surgery, are discussed. The authors suggest
that a unified approach from the various recreational SCUBA diving organizations
involved would aid in clarification for divers and physicians alike. The
difficulties in achieving such a unified approach, however, should not be
underestimated.
PMID- 17040583
TI - Spinal accessory nerve function after neck dissections.
AB - The aim of this study was to evaluate spinal accessory nerve function after
functional neck dissection (FND) and radical neck dissection (RND) by monitoring
the nerve with electromyographic (EMG) examinations. A prospective, double-blind,
clinical study was undertaken in 21 patients (42 neck side dissections) operated
on for head and neck malignant diseases, separated into two groups: 10 neck sides
in the RND group and 32 neck sides in the FND group. Electromyographic
examinations were performed pre-operatively and post-operatively in the third
week and third and ninth months. Additionally, a questionnaire, modified from the
neck dissection impairment index, was applied to all the patients in order to
assess shoulder function in the ninth post-operative month. All patients had
maximum EMG scores pre-operatively. Following the operation, motor amplitudes
decreased in both groups. At the third post-operative month, amplitudes decreased
to their lowest values. As expected, the decreases in amplitude and EMG score
were more prominent in the RND group. Following reinnervation, the amplitudes of
the trapezius motor response increased in the FND group but never reached pre
operative values (during the time of follow up). The FND group scores for pain,
neck and shoulder stiffness, and disability in heavy object lifting, light object
lifting and reaching overhead were significantly lower than those of the RND
group. In FND, one aims to preserve anatomically the spinal accessory nerve, and
it is presumed to be intact after the procedure. However, using EMG nerve
function monitoring, our study revealed that profound spinal nerve injury was
detected immediately after FND surgery, which tended to improve over subsequent
months but had not regained its original function by the end of the ninth post
operative month.
PMID- 17040584
TI - Multifocal bigerminal mature teratomas of the head and neck.
AB - Teratomas and dermoids or hairy polyps of the head and neck are rare congenital
tumours, often confused and reported to appear as single masses, that may cause
upper aerodigestive tract impairment. Their histological classification, origin
and embryological basis of development have been a topic of debate in the past
and recent literature. We report a case of an infant presenting with a multifocal
bigerminal teratoma in the nasopharynx and the neck, causing a deep neck
infection, and discuss the unique clinicopathological aspects of this case.
PMID- 17040585
TI - A multivariate analysis of the factors predicting hearing outcome after surgery
for cholesteatoma in children.
AB - OBJECTIVE: To explore factors influencing hearing outcomes in children treated by
canal wall up (CWU) and canal wall down (CWD) mastoid surgery. METHODS:
Retrospective cohort study including three units in Bristol and Bath, UK. Ninety
consecutive children underwent cholesteatoma mastoid surgery, with the first
procedure between 1998 and 2001; minimum follow up was three disease-free years.
RESULTS: The CWU and CWD cohorts significantly differed in pre-operative stage
and hearing. After disease eradication, air conduction (AC) thresholds changed by
+4.0 dB (95 per cent confidence intervals (95% CI) -2.0, 10.1) in the CWD group
and -5.3 dB (95% CI -9.3, 1.3) in the CWU group (p=0.029). Using multiple linear
regression to account for cohort differences, AC thresholds were increased by:
pre-operative AC threshold (p<0.0001), initial ossicular stage (p=0.013), and CWD
surgery (p=0.005). CONCLUSION: Disease-free hearing was better with CWU-surgery,
less initial ossicular damage, and better pre-operative hearing. Worse initial
disease increased the likelihood of CWD surgery. Wider use of ossiculoplasty in
the CWU cohort (51 per cent vs 5 per cent) may partially explain the superior
results.
PMID- 17040586
TI - Pneumosinus dilatans: demonstrated by sinus expansion on serial sinus X-rays with
discussion of possible aetiology.
AB - A case of pneumosinus dilatans of the frontal sinus is presented. The findings on
serial skull X-rays, performed on three occasions over a 10-year period, seem to
support a developmental aetiology for this rare condition.
PMID- 17040587
TI - Can we improve dysphagia referrals?
AB - We set out to examine whether a multidisciplinary out-patient dysphagia referral
triage service would shorten the duration of a patient's referral process and
direct patients to the correct specialty. A review was carried out of patients
referred with dysphagia before and after the introduction of a multidisciplinary
out-patient dysphagia service, from February 2001 to April 2001 and from January
2002 to March 2002, inclusive. One hundred and eight patients were referred in
total. The length of time until the first appointment was reduced from four to
three weeks (median; range one to 23; p<0.001). The number of instrumental
investigations was reduced, with a median of one instrumentation per patient
under the new service, compared with two in those under the standard service
(p<0.001). Attendance to hospital was also reduced, with 45 per cent of patients
under the new service requiring only one appointment, compared with 13 per cent
in those under the standard service (p<0.001). The multidisciplinary out-patient
dysphagia service was associated with significant reductions in waiting times, in
the number of instrumental investigations and in the duration of the patient's
referral process.
PMID- 17040588
TI - Etanercept, a tumour necrosis factor alpha receptor antagonist, and methotrexate
in acute sensorineural hearing loss.
AB - Patients with autoimmune inner-ear disease (AIED) are treated with high doses of
steroids in the short term when suffering an acute hearing loss. As a
consequence, substances such as methotrexate have been employed in the role of
steroid-sparing agents. Additionally, it is known that tumour necrosis factor
alpha (TNFalpha) is an important mediator of the inflammatory process, inhibition
of which may be of benefit in AIED. This case report illustrates the use of a
TNFalpha inhibitor in combination with methotrexate, which is known to be an
effective combination in rheumatoid arthritis but has yet to be described for
sensorineural hearing loss. We conclude that progressive AIED may respond well to
TNFalpha inhibition, whilst more difficult cases, such as this example, could
benefit from combining such therapy with methotrexate.
PMID- 17040589
TI - Timing of co-phenylcaine administration before rigid nasendoscopy: a randomized,
controlled trial.
AB - Rigid nasendoscopy is a commonly used method of examining the nasal cavity and
postnasal space. Co-phenylcaine is useful for its vasoconstrictive and
anaesthetic properties, but the length of time allowed for it to take effect is
variable. We performed a single-blind, randomized, controlled trial to determine
whether it was better to allow one or 10 minutes for co-phenylcaine to take
effect. Fifty patients were randomized into two groups, 25 in each. Patients in
the 10 minute group experienced less discomfort (p=0.02) and less pain (p=0.018)
than those in the one minute group. Ease of examination was also greater in the
10 minute group, as was the quality of the image obtained (p<0.001).
PMID- 17040590
TI - Role of mitomycin C in reducing adhesion formation following endoscopic sinus
surgery.
AB - OBJECTIVE: To study the role of mitomycin C in reducing adhesion formation
following endoscopic sinus surgery. STUDY DESIGN: Prospective, randomized,
controlled trial. SETTING: Tertiary care referral centre. PATIENTS: Thirty
patients were selected suffering long-term problems with bilateral chronic
rhinosinusitis, with no relief obtained from medical therapy. Patients requiring
revision sinus surgery or having acute upper respiratory tract infection were
excluded. INTERVENTIONS: Diagnostic nasal endoscopies and non-contrast
computerized tomography of nose and paranasal sinuses were undertaken and,
following confirmation of the diagnosis, functional endoscopic sinus surgery
(FESS) was carried out bilaterally using the Messerklinger technique. On
completion of the surgery, a cotton wick soaked in mitomycin C was placed in one
or other side of the nose in the middle meatus. Follow up was for three months
and patients were assessed for subjective and objective improvement in their
symptoms. RESULTS: Post-operatively, of the 11 (36.6 per cent) patients
complaining of persistent nasal obstruction, nine had complaints limited to the
control side only (p=0.005). Out of the nine (30 per cent) patients complaining
of recurrent nasal discharge, eight had complaints on the control side and only
one reported discharge from both sides (p=0.006). CONCLUSION: Mitomycin C may be
topically applied in post-operative FESS cases to reduce adhesion formation and
hence the need for revision surgery.
PMID- 17040591
TI - Surgical management of only hearing ears with positive indications.
AB - Positive surgical indications for an only hearing ear were evaluated in order to
improve patients' quality of life. Fifteen cases of surgery involving an only
hearing ear over the past eight years were retrospectively reviewed. Of eight
perforated chronic otitis media cases, seven underwent type one tympanoplasty and
one underwent simple underlay myringoplasty regardless of otorrhoea at the time
of surgery. Of six cholesteatoma cases, two received the canal wall up method and
four received the canal wall down method. Ossiculoplasty was carefully performed
in six cases. Hearing was improved in seven cases, whereas it remained unchanged
in seven cases and deteriorated in one case. Of nine patients, two did not need a
hearing aid after surgery. Five patients with severe combined hearing loss (>90
dB) were able to communicate with a hearing aid, alleviating their anxiety
regarding hearing loss. Only hearing ears with chronic otitis media and
cholesteatoma can be successfully treated by tympanoplasty with or without
ossiculoplasty.
PMID- 17040592
TI - Role of information leaflets in improving the practice of informed consent for
patients undergoing septoplasty.
AB - AIM: To evaluate the effectiveness of an information leaflet in improving patient
understanding of the procedure and complications of septoplasty. DESIGN: The
baseline knowledge of a group of patients who had attended a pre-assessment
clinic prior to septoplasty was assessed. The procedure and its complications
were then verbally explained. The patients' knowledge was then re-assessed on the
morning of surgery and any improvements noted. In the second arm of the study, an
information leaflet was introduced at the time of verbal instruction and any
differences in improvement in knowledge were assessed. RESULTS: Data from the two
groups were analysed using an analysis of covariance with differences in baseline
(pre-instruction) knowledge controlled. Additional improvements in mean recall
score following leaflet distribution were highly statistically significant when
compared with mean recall in the control group (p<0.001). CONCLUSION: The use of
information leaflets increases patients' knowledge about a surgical procedure and
its potential complications.
PMID- 17040593
TI - Investigation of interleukin 10, 12 and 18 levels in patients with head and neck
cancer.
AB - Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial
malignancy. It is the most common neoplasm arising in the upper aerodigestive
tract. Interleukin (IL) 12 and IL-18 are cytokines which have a major anti-tumour
activity via stimulation of a T-helper type 1 (Th1) immune response. Interleukin
10, a potent antagonist of IL-12, is a cytokine which possesses immunosuppressive
activity mainly produced via T-helper type 2 (Th2) cells. Studies of other types
of cancer have shown that the level of IL-12 in serum or tissues is suppressed
and/or the IL-10 level is increased, suggesting that there is an impaired cell
mediated anti-tumour response. The aim of this study was to measure pre-operative
serum cytokine concentrations in HNSCC patients in order to detect any changes in
IL-10, IL-12 and IL-18, compared with non-tumour controls. The relationship
between cytokine levels and standard clinicopathological features, including
tumour site, tumour stage and presence of nodal metastasis, was also examined.
Fifty-seven patients with primary HNSCC were prospectively recruited, together
with 40 non-tumour control patients with a similar age and sex distribution.
Serum cytokine levels were measured using commercial quantitative enzyme-linked
immunosorbent assay. The HNSCC patients had significantly lower IL-12 levels
(median; interquartile range) than controls (42.8 pg/ml, 26.2-61.6 vs 52.3 pg/ml,
37.5-113.7; p=0.018). Also, patients were more likely to have detectable IL-10
levels than were controls, as IL-10 was positive in 27/55 patients but in only
9/39 controls (p=0.011). Furthermore, IL-10 detectability varied according to
primary site, being more commonly observed in hypopharyngeal and laryngeal
tumours, and IL-10 was more likely to be detected with advanced tumour stage (T3
and T4). No differences in IL-18 levels were observed between patients and
controls (p=0.169). These results suggest (in agreement with studies on other
solid malignancies) that HNSCC causes a significant change in the serum levels of
specific Th1 and Th2 cytokines, producing an in vivo environment that is unlikely
to promote an effective cell-mediated anti-tumour response.
PMID- 17040594
TI - Idiopathic maxillary antral mucocele in a child: a rare presentation.
AB - We report a case of a large maxillary sinus mucocele in a 14-year-old girl
presenting with epiphora, proptosis and dental pain. This was marsupialized
endoscopically, with complete resolution of symptoms over three months' follow
up. The literature is reviewed.
PMID- 17040595
TI - Departmental audit of tonsillectomy haemorrhage rates: pitfalls in
interpretation.
AB - Concerns that a largely anecdotal increase in post tonsillectomy haemorrhage
rates was related to the introduction of disposable instruments have prompted
much investigation. The result has been, rather, to highlight other variables
influencing this risk, but especially to insist on the following: 1. Training in
traditional 'cold' techniques. 2. Regular departmental audit of haemorrhage
rates. 3. Presentation of such data to patients to ensure informed consent. This
audit demonstrates the pitfalls in interpretation of crude data, unadjusted for
case-mix, in predicting individual patient risk and in national ranking of unit
performance.
PMID- 17040596
TI - Laryngeal cancer after topical mitomycin C application.
AB - Mitomycin C is part of the mitomycin group of antibiotics and has found use in
medicine in the treatment of various cancers, including those of the head and
neck. In recent years, it has gained popularity as a topical treatment to prevent
scar formation in the larynx and choanae in paediatric and adult inflammatory
processes. Also, this alkylating agent is potentially a potent carcinogen. We
report the first case in the world literature of laryngeal carcinoma in a non
smoking adult, which may have been induced by topical mitomycin C application to
a glottic web. We discuss the mechanism of action of this drug, and we advise
caution on its use for benign laryngeal pathologies.
PMID- 17040597
TI - Tinnitus and Paget's disease of bone.
AB - AIM: To investigate the prevalence of tinnitus and deafness in subjects with
Paget's disease of bone. MATERIALS AND METHODS: One hundred and thirty-four
subjects in total (77 with Paget's disease) were identified and audiologically
examined. Subjects' experience of tinnitus was surveyed via a questionnaire and
the results compared with those of age-matched controls. RESULTS: Hearing loss in
those with Paget's disease of bone was significantly worse than in controls.
Hearing handicap was also much worse in the Paget's subjects. Sixty-one per cent
of the Paget's subjects suffered from tinnitus, compared with 36 per cent of the
controls. CONCLUSION: Deafness is a recognized, common sequelae of Paget's
disease of bone, and tinnitus is a common accompanying symptom.
PMID- 17040598
TI - Prospective study of the microbiological flora of hearing aid moulds and the
efficacy of current cleaning techniques.
AB - INTRODUCTION: Wearing hearing aid earmoulds has been implicated as a predisposing
factor in the development of chronic otitis externa. Audiologists come into
contact with a large number of hearing aid earmoulds and these could potentially
harbour pathogenic micro-organisms, with the risk of subsequent cross infection.
Cleaning with dilute alcohol is widely used in an attempt to break the chain of
infection. OBJECTIVE: To determine the presence and nature of microbial flora on
hearing aid earmoulds and the efficacy of cleaning methods used to prevent cross
infection. SETTING: Secondary health care within the audiology department of
Addenbrooke's Hospital, Cambridge, UK. DESIGN: A prospective, observational
study. METHODS: Hearing aid earmoulds were swabbed before and after cleaning.
Samples were cultured to determine qualitatively and quantitatively the
microbiological flora present before and after cleaning. RESULTS: Twenty out of
21 (95 per cent) earmoulds had microbes present and, of these, 19/20 (95 per
cent) had a polymicrobial profile. Coagulase negative staphylococci and
diphtheroids were the most frequent microbial isolates, but pathogenic bacteria
and fungi were also demonstrated on earmoulds both before and after cleaning.
CONCLUSIONS: The polymicrobial flora, including recognized pathogens, that
colonizes earmoulds may lead to chronic otitis externa. Cleaning with 70 per cent
alcohol solution was ineffective, in particular for pathogenic fungi on
earmoulds.
PMID- 17040599
TI - Anaplastic thyroid carcinoma implantation after fine needle aspiration cytology.
AB - We report the case of a 59-year-old man with a two-month history of a fast
growing, left-sided neck mass and a 5 mm nodule over a thyroid mass at the site
of fine needle aspiration cytology performed four weeks earlier.
Histopathological studies confirmed anaplastic carcinoma of the thyroid and
cutaneous needle track seeding of the primary tumour. The patient succumbed to
extensive disease 10 weeks after initial diagnosis. To our knowledge, this is a
rare report of implantation of anaplastic thyroid carcinoma along the track of
fine needle aspiration. Some factors involved in needle track seeding are: needle
size; number of passes; withdrawing the needle without releasing suction;
injecting the tumour at time of biopsy; and inherent characteristics of the
lesion (e.g. number of cells dislodged, adhesiveness of cells, amount of stroma
present, enzymes released and immunologic characteristics).
PMID- 17040600
TI - Pre-vertebral surgical emphysema following functional endoscopic sinus surgery.
AB - Functional endoscopic sinus surgery (FESS) is a widely practiced technique in the
UK. This procedure has variable complication rates and can have some serious
consequences. We present a case of surgical emphysema of the neck, face and the
pre-vertebral space following FESS. Emphysema of the face and neck has been
previously reported. However, to our knowledge, emphysema of the pre-vertebral
space following FESS has not been documented. Pre-vertebral emphysema following
FESS is an unusual and potentially serious complication.
PMID- 17040601
TI - Radiofrequency ablation (coblation): a promising new technique for laryngeal
papillomata.
AB - This paper describes a new application for radiofrequency ablation in head and
neck surgery. Two patients with extensive laryngeal papillomata were successfully
treated using this technology. The technique is described in detail, highlighting
the main benefits of this approach as compared with existing techniques. These
advantages include limited damage to underlying tissues and a bloodless field.
PMID- 17040602
TI - Management of surgical airway emergencies by junior ENT staff: a telephone
survey.
AB - OBJECTIVE: To determine levels of confidence in the management of surgical airway
emergencies by junior ENT staff. DESIGN: Telephone survey. PARTICIPANTS: 100
Senior House Officers (SHOs) from 100 hospitals in the UK, providing 24 hour
first on-call emergency ENT cover. METHOD: A list of questions was put to
participants. The effects of different variables on confidence with airway
emergencies and what SHOs considered to be adequate training were compared.
RESULTS: Most SHOs provided cover for the management of surgical airway
emergencies. Many of the participants were not confident to handle airway
emergencies or felt that their training was inadequate. As expected, the amount
of previous experience in ENT and the ability to perform advanced airway
procedures gave SHOs greater confidence, but attendance at airway courses did
not. CONCLUSION: Confidence in the management of airway problems is variable and
does not correlate well with perceived adequacy of training. We suggest that
systems of training in airway management are improved. Training issues may be
better approached at an individual level, where deficiencies can be addressed.
PMID- 17040603
TI - A comparison of the incidence of facial palsy following parotidectomy performed
by ENT and non-ENT surgeons.
AB - OBJECTIVE: To compare the complication rates of parotidectomy operations on
benign histology performed by ENT and non-ENT surgeons. STUDY DESIGN AND SETTING:
A seven-year (1994-2000) retrospective case notes review of patients undergoing
parotidectomy in a United Kingdom district general hospital was performed.
Patients with malignant histology were excluded. PARTICIPANTS: Patients were
identified from the hospital computer database. One hundred and fifty-nine
patients underwent parotidectomy for both benign and malignant conditions over
the seven-year period. One hundred and thirty-seven (86 per cent) patients had
parotidectomy for benign conditions and were included in this study. MAIN OUTCOME
MEASURES: The presence or absence of facial palsy and other associated
complications following parotidectomy surgery in both groups. RESULTS: The
temporary facial palsy rates for ENT and non-ENT surgeons were 56 per cent and 57
per cent, respectively. The permanent facial palsy rates for ENT and non-ENT
surgeons were 2 per cent and 7 per cent, respectively. Differences in facial
palsy were not statistically significant. The difference in other complication
rates such as Frey's syndrome, haematoma, salivary fistula, and neuroma were also
not statistically significant. CONCLUSION: Our complication rates were comparable
with published results. There was no significant difference in the observed rate
of post-operative facial nerve palsy and other known complications following
parotid surgery performed by ENT and non-ENT surgeons.
PMID- 17040604
TI - Methicillin resistant Staphylococcus aureus: is it a problem for nasal surgery?
AB - Methicillin resistant Staphylococcus aureus (MRSA) is becoming ever more
prevalent in the UK, and the proportion of MRSA to methicillin sensitive
Staphylococcus aureus (MSSA) seems to be increasing. New strains of MRSA are ever
developing resistance to antibiotic treatment, increasing morbidity and mortality
of infection. Staphylococcus aureus is part of the normal flora of the nose, and
MRSA colonizes the nose in infection. However, nasal surgery is rarely
complicated by staphylococcal infections, and MRSA infection following nasal
surgery is rare. The authors present a literature review of MRSA infection, its
relation to the nasal cavity, and infection following nasal surgery.
PMID- 17040605
TI - A correlative study of NF-kappaB activity and cytokines expression in human
chronic nasal sinusitis.
AB - A growing body of literature suggests that cytokines play an important part in
the pathogenesis of chronic nasal sinusitis. However, the mechanism by which the
expression of cytokines in chronic nasal sinusitis is upregulated has not been
well documented. The present study investigated the role of nuclear factor-kappa
B (NF-kappaB) activation in upregulating the expression of interleukin-5, -6 and
8 (IL-5, IL-6 and IL-8). We titrated the levels of IL-5, IL-6 and IL-8 in nasal
mucosa in 52 cases of chronic nasal sinusitis and 12 normal subjects using enzyme
linked immunosorbent assay. According to whether allergic rhinitis was associated
or not, we subdivided the patients into the AR group (with allergic rhinitis) and
the NAR group (without allergic rhinitis). Semi-quantitative reverse
transcription-polymerase chain reaction and immunohistochemical staining were
used to evaluate expression and activation of NF-kappaB P50 and P65 subunits in
nasal mucosa. The correlation between activities of P50 and P65 and cytokines
expression was analysed. Our results showed that IL-5, IL-6 and IL-8 in both the
AR and NAR groups were strikingly elevated in comparison with the control group
(all p < 0.01 for AR group; p < 0.05, 0.05, 0.01, respectively, for NAR group);
and they were even higher in the AR group than those in the NAR group (p < 0.01,
0.05, 0.01, respectively). P50 and P65 mRNA levels in both AR and NAR groups were
markedly greater than those in the control group (all p < 0.01); and the AR group
had further higher levels as compared with the NAR group (both p < 0.05).
Immunohistochemical study revealed that nucleus-positive rates of P50 and P65 in
both AR and NAR groups were significantly higher than those of the control group
(all p < 0.01), and they were much greater in the AR group in comparison with the
NAR group (all p < 0.01). Pearson correlation analysis demonstrated that P50 and
P65 nucleus-positive rates were closely correlated with IL-6 and IL-8 levels, but
not IL-5, with a correlation coefficient of 0.49 for P50 and IL-6, 0.54 for P50
and IL-8, 0.61 for P65 and IL-6, and 0.66 for P65 and IL-8 (all p < 0.01). In
conclusion, upregulated expression and activation of NF-kappaB P50 and P65 might
be one of the mechanisms for induction of IL-6 and IL-8 expression in chronic
nasal sinusitis. Association of allergic rhinitis with chronic nasal sinusitis
further enhanced NF-kappaB activity, and subsequently lead to even stronger
expression of IL-6 and IL-8. IL-5 expression appeared to be independent of NF
kappaB pathway in chronic nasal sinusitis.
PMID- 17040606
TI - Actinomycetes colonization of tonsils: a comparative study between patients with
and without recurrent tonsillitis.
AB - OBJECTIVE: To determine the prevalence of tonsillar actinomycetes colonization in
patients with and without recurrent tonsillitis and to study the association of
this condition with recurrent tonsillitis and tonsillar hypertrophy. STUDY DESIGN
AND SETTING: A retrospective study of 834 patients who had undergone
tonsillectomy for recurrent tonsillitis (group A) and for sleep-disordered
breathing without a history of recurrent tonsillitis (group B). RESULTS: The
prevalence of tonsillar actinomycetes colonization was higher in patients who had
undergone tonsillectomy for sleep-disordered breathing (44.1 per cent) than in
patients who had undergone tonsillectomy for recurrent tonsillitis (33.3 per
cent). The prevalence did not differ by sex or age of patient, although the
occurrence rate was higher in the adult compared with the paediatric population.
There was no statistically significant difference between the mean size of the
tonsils removed in the two groups, and actinomycetes colonization did not affect
tonsil size. Histopathological analysis of resected tonsils did not show active
tissue infection. CONCLUSION: The presence of actinomyces does not indicate
active disease. We are of the opinion that, although actinomyces colonization is
more prevalent in patients with sleep-disordered breathing, it does not
contribute to tonsillar hypertrophy nor to recurrent tonsillitis.
PMID- 17040607
TI - Do all epistaxis patients with a nasal pack need admission? A retrospective study
of 116 patients managed in accident and emergency according to a peer reviewed
protocol.
AB - INTRODUCTION: Epistaxis is the most common nasal emergency and if nasal packing
is required this commonly results in admission. METHODS: A literature search
could find no published (UK) protocols for the management of this common
condition in accident and emergency (A&E) departments. This paper presents a
retrospective review of 116 patients with epistaxis, following implementation of
the new peer reviewed protocol in June 2004. RESULTS: Apart from cautery, 62 had
nasal packing inserted. Only 17 required admission. Forty-six patients were
discharged with nasal packing in situ and only seven (16 per cent) returned due
to bleeding. The overall return rate was 11 per cent. DISCUSSION: We feel this is
a safe and logical protocol. Compared to mandatory admission after nasal pack
insertion, we saved 39 admissions in five months. There were also the added
benefits to patients of being able to recuperate at home rather than in hospital
and avoidance of the risk of hospital acquired infection.
PMID- 17040608
TI - Is there objective evidence that septal surgery improves nasal airflow?
AB - OBJECTIVE: To identify any prospective, controlled trials providing objective
evidence of a reduction in nasal airway resistance following nasal septal
surgery, and to undertake a meta-analysis of available data. METHODS: A
systematic review with meta-analysis of data was undertaken. A systematic review
of the literature using a defined search strategy was conducted to identify
papers that used objective methods of airway assessment to evaluate the benefit
of septal surgery. Accepted techniques for objective airway assessment included
acoustic rhinometry, active anterior rhinomanometry and peak nasal inspiratory
airflow. Papers were included based on pre-defined criteria, which included
standardization of techniques as outlined in the guidelines of the 1984 committee
report on the standardization of rhinomanometry. RESULTS: We identified 942
articles, of which 13 were prospective studies evaluating the objective benefit
of nasal septal surgery. Only three of these studies conformed to the inclusion
criteria. A meta-analysis on these papers was performed using the Mantel-Haenszel
method, and this demonstrated an overall reduction in nasal airway resistance
following septal surgery for nasal obstruction (p=0.018). CONCLUSIONS: The
majority of studies evaluating the objective benefit of septal surgery did not
conform to the recommendations of the committee report on the standardization of
rhinomanometry. Only three prospective controlled trials, with pooled data from
141 cases, were identified for meta-analysis. The conclusions that can be drawn
concerning objective improvement in airway function following nasal septal
surgery are therefore limited. More long-term studies, adhering to standardized
techniques, are needed to provide more convincing data.
PMID- 17040609
TI - Electromyography of the cricoarytenoid unit during supracricoid laryngectomy with
a cricohyoidoepiglottopexy procedure.
AB - Two patients who received supracricoid laryngectomy with cricohyoidoepiglottopexy
to treat laryngeal cancers, underwent intra-operative electromyography analysis.
After the lesion was removed and the electrodes were inserted into the remaining
intrinsic laryngeal muscles, the depth of anaesthesia was carefully reduced.
Gentle tactile stimulations were applied to the pharynx to trigger the reflex
movement of the remaining arytenoids. Recordings were made when reflex movement
was achieved. Case one: Electromyography (EMG) of the remaining arytenoid
demonstrated clear phase differences indicating reciprocal activities between the
adductor group (lateral cricoarytenoid muscle, interarytenoid muscle) and the
abductor muscle (posterior cricoarytenoid muscle). Case two: EMG of the remaining
arytenoid demonstrated reciprocal activities between the interarytenoid muscle
and the posterior cricoarytenoid muscle. Activity of the lateral cricoarytenoid
muscle was not evident because the muscle was excised during removal of the
paraglottic space. Mobility of the arytenoid was attributed to interaction
between the interarytenoid muscle and posterior cricoarytenoid muscle. Reciprocal
interaction between the interarytenoid muscle and posterior cricoarytenoid muscle
alone is also capable of maintaining post-operative laryngeal functions after
supracricoid laryngectomy with cricohyoidoepiglottopexy.
PMID- 17040610
TI - Copying clinic letters to patients: a survey of patient attitudes.
AB - Guidance from the Department of Health, published in 2000, stated that, 'as a
matter of right', communications between clinicians would be copied to patients.
In further guidance, the department indicated that, from April 2004, patients
would receive copies of correspondence exchanged between healthcare
professionals. There has been little research on this issue, and the few existing
publications have come from the hospital psychiatric clinic setting. We examined
the attitudes of 100 patients attending an ENT clinic as well as those of 100
parents of children attending a paediatric ENT clinic in a general hospital out
patient setting. At the end of consultations, patients or parents were invited to
take part in the survey by completing a short questionnaire. Forty-three per cent
of the adult patients and 44 per cent of the parents requested a copy of the
clinic letter. These people were followed up by a telephone survey, three weeks
after the copy of the clinic letter to the general practitioner was posted to the
patient or parent. Eighty-one per cent of the patients and 77 per cent of the
parents were successfully contacted for the follow-up telephone survey. Sixty per
cent of the adults and 77 per cent of the parents reported that the copy of the
clinic letter was helpful. There were no differences in responses between the
adult patient and paediatric patient groups. In this study, less than half of
both groups requested a copy of the ENT clinic letter to their general
practitioner. To follow Department of Health guidance and copy the letter without
patient consent is arguably contradictory to best practice and also to the
concept of patient choice. There are significant financial implications in
adopting the departmental guidance. We propose patients should be offered a copy
of their clinic letter on request.
PMID- 17040611
TI - Early pulmonary response in rats infected with Trichinella spiralis.
AB - The migratory stage of Trichinella spiralis, the newborn larva, travels along the
pulmonary microvascular system on its way to the striated muscle cells. In the
present study, an important inflammatory reaction was observed on days 5 and 14
post-infection (p.i.) in the lungs of infected rats. This inflammation was
characterized by a Th2 cell phenotype of hyperplastic bronchus-associated
lymphoid tissue and by goblet cell hyperplasia. Among the inflammatory cells were
eosinophils and mast cells scattered over the pulmonary parenchyma. On day 5 p.i.
the number of IgE(+), CD4(+) and CD5(+) cells in the bronchus-associated lymphoid
tissue were increased and IgE-secreting lung cells were also detected. At the end
of the migratory phase of the infection (day 14 p.i.), only IgE(+) cells were
detected in high numbers and in the bronchoalveolar lavage fluid, an increment in
the total IgE levels as well as the presence of IgE and IgA anti-larvae surface
were also detected. In cytotoxicity assays, cells from the bronchoalveolar lavage
had considerable biological activity since they were able to kill the larvae even
in the absence of specific antibodies. These results show that the lung is an
organ involved in the immune response developed early during a T. spiralis
infection and suggest its importance in the protection of the host.
PMID- 17040612
TI - Interactions between parasites of the cockle Austrovenus stutchburyi: hitch
hikers, resident-cleaners, and habitat-facilitators.
AB - The patterns of association between parasites within a particular host are
determined by a number of factors. One of these factors is whether or not
infection by one parasite influences the probability of acquiring other parasite
species. This study investigates the pattern of association between various
parasites of the New Zealand cockle Austrovenus stutchburyi. Hundreds of cockles
were collected from one locality within Otago Harbour, New Zealand and examined
for trematode metacercariae and other symbionts. Two interspecific associations
emerged from the study. First, the presence of the myicolid copepod Pseudomyicola
spinosus was positively associated with higher infection intensity by
echinostomes. The side-effect of the copepod's activities within the cockle is
suggested as the proximate mechanism that facilitates infection by echinostome
cercariae, leading to a greater rate of accumulation of metacercariae in cockles
harbouring the copepod. Second, a positive association was also found between
infection intensity of the metacercariae of foot-encysting echinostomes and that
of gymnophallid metacercariae. This supports earlier findings and suggests that
the gymnophallid is a hitch-hiker parasite because, in addition to the pattern of
positive association, it (a) shares the same transmission route as the
echinostomes, and (b) unlike the echinostomes, it is not capable of increasing
the host's susceptibility to avian predation. Thus, both active hitch-hiking and
incidental facilitation lead to non-random infection patterns in this parasite
community.
PMID- 17040614
TI - Cochlear implantation in the irradiated temporal bone.
AB - OBJECTIVE: To demonstrate the feasibility and complexities of cochlear
implantation in the setting of bilateral temporal bone osteoradionecrosis. STUDY
DESIGN: Case report. SETTING: Tertiary care referral centre. CASE DESCRIPTION: A
66-year-old woman with bilateral temporal bone osteoradionecrosis and profound
hearing loss, following treatment for tonsillar cancer, underwent cochlear
implantation. Prior canal wall down mastoidectomy and subsequent temporal bone
resection with free flap reconstruction had been performed on the implanted ear.
The contralateral ear received a canal wall down mastoidectomy. A completely
dehiscent mastoid segment of the facial nerve and extensive fibrosis were evident
in the implanted ear. Only minimal fibrous reaction was found within the cochlea,
allowing for full electrode insertion. At three months, speech recognition
testing documented a consonant-nucleus-consonant (CNC) word score of 54 per cent.
CONCLUSIONS: This report demonstrates the feasibility of cochlear implantation
after temporal bone surgery and free flap reconstruction in the setting of
diffuse osteoradionecrosis. The patient's excellent open-set speech understanding
using the cochlear implant implies that radiation did not severely damage the
central auditory pathways. Thus, some patients with radiation-induced hearing
loss may be appropriate cochlear implant candidates. Special attention should be
paid to surgical planning, as complications related to wound healing, electrode
insertion and facial nerve injury may be more likely.
PMID- 17040615
TI - Application of ligating loops to control bleeding during endoscopic surgery for a
highly vascular hypopharyngeal tumour.
AB - Endoscopic treatment of hypervascular lesions of the hypopharynx is challenging
because of difficulty in controlling bleeding during surgery. We report a highly
vascular hypopharyngeal solitary fibrous tumour treated by endoscopic laser
surgery combined with ligating loops. Application of dual ligating loops provided
easy and secure haemostasis of the feeding artery before resection. Since the
endoscopic approach is less invasive than the external approach, we confirm that
it is worthwhile to attempt an endoscopic approach using ligating loops before
resorting to the external approach in the treatment of hypervascular
hypopharyngeal lesions.
PMID- 17040613
TI - Determination of thermodynamics and kinetics of RNA reactions by force.
AB - Single-molecule methods have made it possible to apply force to an individual RNA
molecule. Two beads are attached to the RNA; one is on a micropipette, the other
is in a laser trap. The force on the RNA and the distance between the beads are
measured. Force can change the equilibrium and the rate of any reaction in which
the product has a different extension from the reactant. This review describes
use of laser tweezers to measure thermodynamics and kinetics of
unfolding/refolding RNA. For a reversible reaction the work directly provides the
free energy; for irreversible reactions the free energy is obtained from the
distribution of work values. The rate constants for the folding and unfolding
reactions can be measured by several methods. The effect of pulling rate on the
distribution of force-unfolding values leads to rate constants for unfolding.
Hopping of the RNA between folded and unfolded states at constant force provides
both unfolding and folding rates. Force-jumps and force-drops, similar to the
temperature jump method, provide direct measurement of reaction rates over a wide
range of forces. The advantages of applying force and using single-molecule
methods are discussed. These methods, for example, allow reactions to be studied
in non-denaturing solvents at physiological temperatures; they also simplify
analysis of kinetic mechanisms because only one intermediate at a time is
present. Unfolding of RNA in biological cells by helicases, or ribosomes, has
similarities to unfolding by force.
PMID- 17040616
TI - Parental satisfaction with health services provided to children with Down
syndrome in north-west England: an ENT perspective.
AB - AIMS: To evaluate parents' satisfaction with medical and allied health services
provided to children with Down syndrome in north-west England, comparing ENT and
its allied services with other areas of health service provision. METHODS: A
questionnaire survey of parents attending a north-west England Down syndrome
association conference. Demographic data, departments visited, satisfaction with
each service (scored one to five), waiting times for each service (scored one to
five), service need (scored one to three) and accessibility (scored one to three)
were recorded. RESULTS: Otolaryngology had been used by 50 per cent of children,
with a satisfaction of 2.63 (the second worst score). Speech and language therapy
was used by 90 per cent of the children, with a satisfaction of 3.26 (the worst
score). The service felt to be most needed and also most difficult to access was
speech and language therapy. CONCLUSION: Otorhinolaryngology departments should
assess how they can improve their service to this population with specific ENT
needs. Speech and language services for children with Down syndrome should be
expanded.
PMID- 17040618
TI - Induction therapy for adults with acute lymphoblastic leukemia.
PMID- 17040617
TI - Evaluation of the clinical utility of diagnostic versus therapeutic interventions
in oncology: related but quite different processes.
PMID- 17040619
TI - Improving outcomes in difficult bone cancers using multimodality therapy,
including radiation: physician and nursing perspectives.
AB - Principles of therapy are similar for Ewing's sarcoma and osteosarcoma.
Chemotherapy or surgery alone cures few patients. Multimodality measures are
needed for durable response. Quality of life and function are very important
short- and long-term considerations. The spine, sacrum, pelvis, ankle, hand,
mediastinum, pulmonary hilum, and chest wall are examples of bone cancer
locations for which surgery is difficult. Patients with positive margins may need
radiation and may experience systemic therapy delay, recurrence, loss of
function, or any combination of these. When radiation is used as a means of local
control, concomitant chemotherapy can increase its effectiveness. Options for
difficult Ewing's sarcoma and osteosarcoma situations and multimodality
solutions, including 1 mCi/kg of samarium and proton therapy, are discussed.
Combination radiation and chemotherapy regimens are summarized, and organization
of patients, caregivers, and medical teams for multimodality therapy is
described, along with tools used in our institution that aid in this process.
PMID- 17040620
TI - Molecular genetics of pediatric central nervous system tumors.
AB - Recent advances in molecular biology have enhanced our understanding of the
pathogenesis of brain tumors, particularly in children. The use of molecular
diagnostic tools is quickly becoming a standard component in the diagnosis and
classification of brain tumors in children, in addition to providing insight
leading to treatment stratification and improved outcome prediction. All new
protocols involving treatments for brain tumors in children include studies of
biomarkers and biologic correlates as a means to identify new targets for
therapeutics and possible intervention strategies.
PMID- 17040621
TI - Induction of apoptosis in lymphoid and myeloid leukemia.
AB - Defects in the core machinery of the apoptosis pathway contribute to
chemoresistance and poor outcomes in patients with acute leukemia. To overcome
these defects, novel molecules that target key proteins in the apoptosis pathway
are being developed. This review highlights compounds that target the
mitochondrial, death receptor, and convergence pathways of caspase activation
that are being developed for the treatment of acute leukemia.
PMID- 17040622
TI - Gene therapy for ovarian cancer.
AB - Ovarian cancer remains the leading cause of death due to gynecologic cancer in
women in the United States. Gene and viral-based therapies represent novel
therapeutic approaches for cancer. The manipulation of genetic content of tumor
cells toward a therapeutic end has been divided into several general strategies,
including molecular chemotherapy, mutation compensation, immunopotentiation, and
virotherapy. Improvements in delivery vehicles and in evaluation of gene transfer
and viral replication remain important areas of investigation. We highlight the
most recent advances in these novel therapeutic approaches for ovarian cancer and
include a summary of recent clinical trials.
PMID- 17040623
TI - The current treatment of recurrent ovarian cancer.
AB - Contemporary management of recurrent ovarian, primary peritoneal, and fallopian
tube cancers has continued to evolve and now offers women the hope of extended
survival with an improved quality of life. Platinum continues to be the single
most active agent in the treatment of ovarian cancer, but acquired resistance to
platinum often emerges. Fortunately, a number of novel agents and treatment
strategies have been developed to meet the goals of ameliorating symptoms while
extending survival. Classically, patients have been treated based upon the
interval from last platinum administration during front-line therapy until time
of recurrence. This review focuses upon the current treatment strategies used for
platinum-refractory, platinum-resistant, and platinum-sensitive patients. The
incorporation of targeted biologic agents is also discussed, along with the role
of secondary cytoreduction. It is hoped that the results of future and ongoing
clinical trials will offer further advances in the treatment of this devastating
disease.
PMID- 17040624
TI - Historical progress in the initial management of ovarian cancer: intraperitoneal
chemotherapy.
AB - Despite measured improvement in survival with the introduction of the platinates
and taxanes in treatment of advanced ovarian cancer, little additional progress
has been made with conventional cytotoxic agents. Recently, the Gynecologic
Oncology Group (GOG) published data from a study evaluating the merits of
intraperitoneal chemotherapy in women with advanced, optimally cytoreduced
ovarian cancer. They documented a significant advantage in progression-free and
overall survival for the experimental regimen, a combination of intravenous
paclitaxel and intraperitoneal cisplatin and paclitaxel, compared with standard
intravenous cisplatin and paclitaxel chemotherapy. The intraperitoneal regimen
was substantially more toxic and was associated with reduced short-term quality
of life. The GOG trial joins six other published phase III trials since 1994
comparing intravenous with intraperitoneal chemotherapy in advanced-stage
epithelial ovarian cancer. A recent meta-analysis suggests a 21% reduction in the
hazard for progression (four studies) and death (seven studies). Reluctance to
adopt a new standard of care is rooted in toxicity concerns. Further evaluation
is warranted to clarify unanswered questions regarding administration schedule,
agents, techniques, number of courses, and patient eligibility for
intraperitoneal chemotherapy.
PMID- 17040625
TI - Current and emerging treatment approaches for tobacco dependence.
AB - Nicotine in tobacco is the primary reason why most people find it hard to stop
using tobacco. Nicotine creates dependence by activating the dopaminergic reward
system in the brain. Physiologic withdrawal symptoms that occur when nicotine is
no longer administered reinforce continued nicotine administration to avoid
withdrawal. Extrapolating from this evidence has led to the development of
tobacco dependence pharmacotherapy based upon the concept of replacing and/or
blocking the effects of nicotine in the brain. The efficacy of nicotine
replacement and blockade treatments in lessening symptoms of nicotine withdrawal
and increasing quit rates has been consistently demonstrated in clinical trials.
Despite the availability of efficacious medications to treat nicotine dependence,
current therapies remain underutilized across the population. Health-care
providers need to systematically encourage all tobacco users to quit and ensure
that their tobacco-using patients use evidence-based treatments when they attempt
to quit.
PMID- 17040627
TI - Screening tests for colorectal cancer: a menu of options remains relevant.
AB - Until the early 1990s, no evidence was available to show that screening for
colorectal cancer (CRC) by any means actually saved lives. Subsequently,
sufficient evidence for the efficacy of fecal occult blood testing (FOBT) and
flexible sigmoidoscopy allowed the US Preventive Services Task Force to publish
guidelines for CRC screening. Since that time the major organizations in the
United States concerned with screening guidelines have recommended a menu of
screening test options including FOBT, flexible sigmoidoscopy, flexible
sigmoidoscopy plus FOBT, barium enema, and colonoscopy. No organization, except
for the American College of Gastroenterology, has designated any one of these
options as "preferred." Nevertheless, the lay press and many gastroenterology
opinion leaders have encouraged Americans to have only one test--colonoscopy. In
this review we discuss the rationale for caution in designating one screening
test as "the best" and present information on how new stool and serum tests can
be used effectively to screen for CRC.
PMID- 17040628
TI - [Spanish version of the DASH questionnaire. Cross-cultural adaptation,
reliability, validity and responsiveness].
AB - BACKGROUND AND OBJECTIVE: The Disabilities of the Arm, Shoulder and Hand (DASH)
questionnaire is a specific outcome instrument developed to measure upper
extremity disability and symptoms. The aim of this work is to develop a Spanish
version of the DASH questionnaire and to analyze its reliability, validity and
responsiveness. MATERIAL AND METHOD: We performed cross-cultural adaptation of
the DASH to Spanish, using a process that included double forward and backward
translations, expert review and field-testing. The Spanish version's reliability,
content, construct and criterion validity and responsiveness were then evaluated
in 98 patients with upper-extremity conditions that completed the DASH and SF-36
generic health questionnaire before and after medical rehabilitation treatment.
RESULTS: We obtained a Spanish DASH version (DASHe) linguistically and
conceptually equivalent to the original version. Internal consistency of the
DASHe was high (Cronbach alpha = 0.96), test-retest reliability was excellent (r
= 0.96) and the floor and ceiling effects were negligible. Construct and criteria
validity was shown by a positive association of DASHe scores with worse
condition, and a significant correlation with the SF-36 scores, stronger with the
SF-36 pain dimension. Responsiveness was excellent (effect size and standardized
response means higher than 0.80). CONCLUSIONS: The DASHe is a reliable, valid and
responsive instrument that can provide a standardized measure in Spanish patients
with upper-extremity musculoskeletal conditions.
PMID- 17040626
TI - Molecular screening for breast cancer prevention, early detection, and treatment
planning: combining biomarkers from DNA, RNA, and protein.
AB - The completion of the human genome project, along with the ancillary technologies
derived from this effort, provides the ability to comprehensively analyze patient
tumors as well as the individual patient's own genetic make-up at the DNA, RNA,
and protein level. As a result, novel molecular screening techniques have the
potential to push the boundaries of detection to even smaller tumors and also to
allow accurate risk assessment, cancer prevention, and treatment planning in
individual women. This review focuses on advances over the past 2 years in the
use of molecular signatures and circulating tumor cells for early breast cancer
detection and for prediction of response to therapy.
PMID- 17040629
TI - [Infectious diarrhea study in Castellon, Spain (EDICS): population incidence of
sporadic cases in 2004 and comparison with the year 2000].
AB - BACKGROUND AND OBJECTIVE: Infectious intestinal diseases are highly prevalent,
and among them sporadic cases are the most common processes. The aim of this
study was to estimate the incidence of sporadic cases diagnosed in a healthcare
district of Castellon (Spain) in the year 2004, and to compare them with those of
the year 2000. MATERIAL AND METHOD: Based on routine coprocultures and individual
demographic data of each patient, we calculated the population rates by age for
the more frequent microorganisms, especially detailed for children up to 5 years
of age. We report the results of the year 2004, and compare these with the
previous study of the year 2000. RESULTS: Campylobacter showed the highest rate
(1.01 x 103), followed by Salmonella (0.75), each without significant differences
regarding the year 2000. The rate of rotavirus cases (0.65) was smaller than in
2000; and for adenovirus 2004 was an atypical seasonal year. In children younger
than 3 years, rates were 26.54; 10.23 and 11.75. As in the previous study, the
age-distribution in children < 5 years was very particular. An U inverted shape
was seen for Campylobacer, and the rates for rotavirus decreased after the peak
observed in the youngest group (< 6 months). Among hospitalized patients
rotavirus was the most common and Campylobacter the less common. CONCLUSIONS: The
epidemiological traits of the rates by age until the age of five are
characteristic for each microorganism, as are the proportions of hospitalization.
Rates of Campylobacter and Salmonella in the year 2004 were similar to the year
2000, but a decrease in the rotavirus rates was observed.
PMID- 17040630
TI - [Swelling of the bronchial mucose and quickness of onset in acute asthma].
AB - BACKGROUND AND OBJECTIVE: The plasma protein leakage produced in the bronchial
mucose of patients with acute asthma might be associated to the quickness of the
onset exacerbation. The aim of this study was to study this association. PATIENTS
AND METHOD: 22 patients with acute asthma were recruited, and the magnitude of
plasma protein leakage was measured by the concentrations of albumin and alpha2
macroglobulin in sputum. RESULTS: Days of onset in acute asthma correlated
negatively with albumin sputum concentration (r = -0.563; p = 0.006), alpha2
macroglobulin sputum concentration (r = -0.603; p = 0.003), and related relative
coefficients of albumin sputum/serum (r = -0.538; p = 0.01) and alpha2
macroglobulin sputum/serum (r = -0.514; p = 0.014). When the sample was divided
by the following daily cutoff: < or = 4, patients suffering from a shorter onset
of acute asthma showed a higher concentration of alpha2-macroglobulin in sputum:
mean (standard deviation) of 14.4 (18) versus 5.3 (5.4) (p = 0.028). CONCLUSIONS:
Plasma protein leakage seems to play an important role in the inflammatory
pathogenesis of asthma exacerbation. The quicker onset of asthma the more plasma
protein extravasation to the bronchial lumen.
PMID- 17040631
TI - [Upper extremity related disorders and quality of life].
PMID- 17040632
TI - [Open access and the Spanish medical journals].
PMID- 17040633
TI - [Pathogenesis of lipodystrophy and metabolic syndromes associated with HIV
infection].
AB - Lipodystrophy, and the metabolic alterations (dislipemia, insulin-resistance)
associated with human immunodeficiency virus (HIV) infection, is a multifactorial
syndrome due to the interaction of host related factors (cellular immune status,
diet, gene mutations), viral factors (cytokine synthesis, polyunsaturated fatty
acid or PUFA depletion), and pharmacological effects (mitochondrial DNA
polymerase inhibition, lipolysis inhibition, adiponectin synthesis reduction).
HIV probably modifies the adipocyte differentiation and the lipid metabolism.
This retroviral effect is mediated by proinflammatory cytokines (tumor necrosis
factor) and the participation of other factors (drugs, diet), all in the context
of a particular host genetic setting. The adipocyte (and several cellular
receptors, fatty acids, membrane proteins, and cytokines) plays a central role in
the pathogenesis of HIV-associated lipodystrophy.
PMID- 17040634
TI - [Lack of compliance of recommendations of endocarditis prophylaxis in
outpatients].
PMID- 17040635
TI - [Prevalence of positive prick-test to latex in the surgical population].
PMID- 17040636
TI - [Agenesia of inferior vena cava in young adults with iliac deep vein thrombosis].
PMID- 17040637
TI - [Epiploic appendagitis: an entity to be considered in the differential diagnosis
of patient with clinical suspicious of appendicitis or diverticulitis].
PMID- 17040638
TI - [Pituitary apoplexy following treatment for acute coronary syndrome].
PMID- 17040639
TI - [Good response to treatment with rituximab in a child with refractory idiopathic
thrombocytopenic purpura].
PMID- 17040640
TI - [Isolated IIIrd nerve palsy as the only sign of chronic subdural haematoma].
PMID- 17040641
TI - [Exposure to risk factors across the life course and cardiovascular disease].
PMID- 17040642
TI - [Prioritizing patients on waiting list for cataract surgery: preference
differences among citizens].
AB - OBJECTIVES: To estimate and compare citizen preferences regarding patient
prioritization for cataract surgery. METHOD: A conjoint analysis was performed.
Priority criteria were identified and selected using 4 focus/nominal groups
consisting of the general public, patients/relatives, allied health-professionals
and specialists from Catalonia (n=36). Preferences elicitation (score of
criteria): representative sample survey of the above mentioned groups (n=771) and
rank-ordered logit model application. Differences were assessed by group analysis
and their comparison. RESULTS: The criteria selected and their relative
importance were: visual impairment (45%), difficulty in performing activities of
daily living (ADL) (15%), limitation of ability to work (14%), being looked after
by someone (11%), being a caregiver (8%), and recovery probability (7%).
Differences in scores were observed among groups. Visual impairment was scored
more highly by the general public and patients/relatives than by other groups
(p<0.001). These two groups also assigned less importance to difficulty in
performing ADL (p<0.001). The probability of recovery was the least scored
criterion by most groups. Correlations among the order of hypothetical patient
scenarios were high (r>0.9). However, the final order of patients on the waiting
list could differ by up to 27 positions when different group scores were applied.
CONCLUSIONS: Social and clinical criteria were considered important. The observed
differences among citizens regarding how to prioritize patients on the waiting
lists indicates the need to take into account the preferences of all groups of
citizens.
PMID- 17040643
TI - [Association of income with use of and access to health services in Spain at the
beginning of the XXI century].
AB - OBJECTIVE: To estimate the association of household income and provincial income
with visits to general practitioners and specialists and with hospitalization and
to determine whether waiting times to access these services vary with both
economic variables. METHOD: Data from the 2001 National Health Survey were used.
The association was estimated by sex- and age-adjusted odds ratios; in the case
of per capita income, odds ratios were also adjusted for household income.
Percentiles and the geometric mean of waiting times in each health service were
estimated and the statistical significance of their association with both
economic variables was evaluated. RESULTS: Subjects with the lowest household
income showed the highest frequency of visits to general practitioners and
hospitalization, although they waited longer for hospital admission. Subjects
with the lowest household income also showed the lowest frequency of specialist
visits: the odds ratio in the lowest income quartile with respect to the highest
income quartile was 0.73 (95% CI: 0.62-0.87). However, when only visits to
specialists working in the public system were analyzed, the lowest frequency of
visits was observed in subjects with the highest household income. No differences
were found in health services utilization or in waiting times according to
provincial income. CONCLUSIONS: The frequency of specialist visits according to
household income shows a different pattern from that observed for visits to
general practitioners and hospitalizations. The longest waiting times for
admission to hospital were observed in subjects with the lowest household income.
PMID- 17040644
TI - [Famine in the Spanish civil war and mortality from coronary heart disease: a
perspective from Barker's hypothesis].
AB - OBJECTIVE: To determine whether the famine experienced during the Spanish civil
war and immediate postwar period influenced mortality from coronary heart disease
(CHD) in persons born in this period, following the lines of Barker's hypothesis
on fetal programming of chronic diseases in adult life. METHODS: Using CHD
mortality data by age and sex for 1990-2002, annual and age-adjusted rates were
calculated by the direct method. Poisson regressions were used to estimate
period, age and cohort effects by year of birth (1918-1957). RESULTS: During the
study period, CHD mortality fell by a yearly average of -2.3% in both sexes and
in all ages yearly. This trend was influenced by both cohort and period effects
(p<0.001); an increased risk was observed for both sexes and in all ages in the
deaths corresponding to persons born during the war and postwar years when the
famine was most intense (1937, 1940, 1943 and 1945). CONCLUSIONS: The results
obtained by studying yearly CHD mortality are compatible with those expected by
Barker's hypothesis of the effect of nutritional stress during pregnancy. In
addition to its human, economic and political costs, the Spanish civil war could
also have had negative consequences for the health of persons born in this
period.
PMID- 17040645
TI - Evaluation of the research methodology in genetic, molecular and proteomic tests.
AB - INTRODUCTION: The advances in genomic analysis technologies have conducted to the
development of new diagnostic tests in the clinical practice. As well as it
happened in other diagnostic fields, the knowledge of the main flaws affecting
genetic investigation will facilitate the application of the results. METHODS: We
included 44 original articles that evaluate diagnostic exactitude of genetic and
molecular tests (including proteomic), published from 2002 to June 2005 in five
international publications: JAMA, Lancet, New England Journal of Medicine, Cancer
Research and Clinical Cancer Research. We examined adherence to 24 methodological
criteria included in the guide STARD (Standards for Reporting of Diagnostic
Accuracy. RESULTS: The mean number of methodological criteria satisfied was 9.8
(95% CI 8.8-10.6); the greater deficiencies were in aspects related to the
description of patient's selection 9 (20%), the treatment of indeterminate
results 5 (11%) and the determination of test reproducibility 6 (13%). It was
observed a high fulfillment in the description of the gold standard 39 (87%) and
in the methodology of the test 28 (62%). DISCUSSION: The methodologic quality of
the evaluated articles is lower than the quality observed in other research
fields. The methodologic aspects that most need improvement are those linked to
the clinical information of the populations studied and the reproducibility of
the tests. The research and development of new genetic-molecular technologies
requires a better fulfillment of the epidemiological and clinical criteria
already followed by other diagnostic fields.
PMID- 17040646
TI - [Safety-engineered devices to prevent percutaneous injuries: cost-effectiveness
analysis on prevention of high-risk exposure].
AB - OBJECTIVE: To assess the efficiency of the replacement of several medical devices
by engineered sharp injury (SI) prevention devices (ESIPDs). METHODS: The cost
effectiveness ratios of the replacement of medical devices in use by ESIPDs were
estimated: their purchasing costs and the direct costs of sharp injury care were
taken into account; the number of SI avoidable by each ESIPD was estimated from
the 252 occupational SI notified by healthcare workers at a 1,300 bed hospital
from March 2002 to February 2003. The relationship between ESIPD additional costs
and the number of high-risk SI was estimated (SI were classified as high-risk if
they met two or more of the following criteria: moderately-deep or deep injury,
injury with a device previously inserted in an artery or vein, or with a device
exposed to blood). RESULTS: ESIPDs order according to cost-effectiveness ratio:
safety needle for implanted ports (-2.65 euro/SI avoided), followed by syringes
with protective shield (869.79 euro/SI), resheathable winged steel needles,
needleless administration sets, and short catheters with protective encasement.
ESIPDs order according to relationship between additional costs and number of
high-risk sharp injuries avoided: safety needles for implanted ports, followed by
winged steel needles, hypodermic syringes, short catheter and needleless
administration sets. CONCLUSIONS: Savings in SI care outweigh additional costs of
certain ESIPDs. Cost-effectiveness analysis is useful in assigning priorities;
however the risks of SI by every device must be taken into account.
PMID- 17040647
TI - [Cost of assisted reproduction technology in a public hospital].
AB - OBJECTIVES: Most studies on the costs of assisted reproductive technologies (ART)
identify the total cost of the procedure with the direct cost, without
considering important items such as overhead or intermediate costs. The objective
of this study was to determine the cost per ART procedure in a public hospital in
2003 and to compare the results with those in the same hospital in 1998. METHODS:
Data from the Human Reproduction Unit of the Virgen de las Nieves University
Hospital in Granada (Spain) from 1998 and 2003 were analyzed. Since the total
costs of the unit were known, the cost of the distinct ART procedures performed
in the hospital was calculated by means of a methodology for cost distribution.
RESULTS: Between 1998 and 2003, the activity and costs of the Human Reproduction
Unit analyzed evolved differently. Analysis of activity showed that some
techniques, such as intracytoplasmic sperm injection, were consolidated while
others, such as stimulation without assisted reproduction or intracervical
insemination were abandoned. In all procedures, unit costs per cycle and per
delivery decreased in the period analyzed. CONCLUSIONS: Important changes took
place in the structure of costs of ART in the Human Reproduction Unit of the
Virgen de las Nieves University Hospital between 1998 and 2003. Some techniques
were discontinued, while others gained importance. Technological advances and
structural innovations, together with a "learning effect," modified the structure
of ART-related costs.
PMID- 17040648
TI - [Comment. On studies of the costs of healthcare processes].
PMID- 17040649
TI - [Smoking cessation in Galician [Spain] smokers during pregnancy and breast
feeding, 1954-2004].
AB - OBJECTIVE: To determine how many women living in Galicia (Spain) quit smoking
during pregnancy and in the first 6 months of breast feeding. A second objective
was to identify possible temporal changes in smoking cessation. METHOD: Data
retrospectively provided by smokers and ex-smokers living in Galicia were
analyzed. RESULTS: A total of 31.9% (26.9-37.0) of Galician smokers did not quit
smoking during pregnancy or in the 6 first months of breast feeding. No
statistically significant differences were found in the percentage of women who
stopped smoking in relation to the period when they became pregnant. A tendency
towards lower cessation rates was found. CONCLUSIONS: A high percentage of
pregnant women do not quit smoking during pregnancy or in the first 6 months of
breast feeding. These data indicate that health policies on smoking during
pregnancy and breast feeding should be improved.
PMID- 17040650
TI - [Evolution of health inequalities in Catalonia [Spain]].
AB - OBJECTIVE: To analyze the evolution of social inequalities in health in Catalonia
(Spain) in the last 20 years. METHODS: Mortality in 354 small areas of Catalonia
(288 cities in Catalonia and 66 health areas in the city of Barcelona) was
analyzed for the 1984-98 period. Indicators of self-perceived health status,
lifestyles, and health services utilization by social class and gender were
compared for 1994 and 2002. Factors related to occupational health, immigration
and health, environmental health, and policies to reduce social inequalities in
health were also analyzed. RESULTS: Although most health indicators improved,
multiple inequalities in health were found in both 1994 and 2002. These
inequalities were the same in 2002 as in 1994 or, in some cases, worse. The
collectives with the worst indicators were persons living in the most deprived
areas, those from disadvantaged social classes, women, and immigrants from low
income countries. CONCLUSION: Social inequalities in health have persisted over
the past 20 years in Catalonia. We present some recommendations on health
information systems, research, and policies to reduce these inequalities.
PMID- 17040651
TI - [Drunk driving in professional drivers in the Via Blanca highway in Cuba].
AB - To determine the frequency of drunk driving in professional drivers (Via Blanca,
Havana City), we carried out a descriptive study of 832 drivers selected by
multistage stratified sampling. A structured interview with each driver was
carried out to record the variables under study, and a breath alcohol test was
subsequently performed. The frequency of drunk driving was 8.18% (95% CI, 5.94%
10.42%), with a predominance of drivers with alcohol levelsor= 64 are considered to be
indicative of recent infection. A number of commercial EIAs have been developped.
The difficulty for IgG interpretation is a definition of a cutoff value for
discriminating infected and healthy subjects. Most of the IgM assays show good
diagnostic sensitivities and are valuable tools for the early diagnosis of
Mycoplasma pneumoniae infection in children. There are no wholly satisfactory
serological methods for diagnosis of Chlamydia pneumoniae infection. Problems
arise from the high background of IgG antibody prevalence, the lack of
standardized testing methods.
PMID- 17040872
TI - [Primary immunodeficiencies and Bruton's disease genetic analysis: which
prospects offers this genetic diagnosis?].
AB - Bruton's disease is the most frequently primary X-linked immunodeficiency.
Bruton's tyrosine kinase (Btk) is encoded by the XLA gene that when mutated
causes bruton's disease. This protein acts in multiple intracellular signaling
pathways where the BCR (B-cell receptor) pathway is the most elucidated. Moreover
400 mutations were found and identified as responsible for B-cells
differentiation block; consequences are a lack of B-cells in peripheral blood and
hypo/agammaglobulinemia. Thus, patients are more susceptible to early and
recurring infections occurring before the age of one year. Laboratory testing
allow differential diagnosis among primary immunodeficiencies in which others
hypogammaglobulinemia. Genetic analyses help physicians for clinical and
biological diagnosis, and allow prenatal diagnosis for patient's family.
Patient's management is based upon polyclonal immunoglobulin supplementation,
infectious diseases prevention and genetic advice.
PMID- 17040873
TI - [Functional characterization of naturally occurring CFTR mutants: interest for
cystic fibrosis].
AB - Cystic fibrosis is caused by mutations in the CFTR gene (Cystic Fibrosis
Transmembrane conductance Regulator) encodes a protein mainly functioning as a
chloride channel that regulates chloride and sodium transport in secretory
epithelial cells. The past several years with advances in DNA analysis have seen
an increased knowledge of the mutational spectrum for cystic fibrosis. The
functional characterization of some naturally occurring CFTR mutants led to
classification of mutations according to the mechanisms by which they disrupt
CFTR function. This article reports the strategies that are currently available
to evaluate the deleterious consequences of naturally occurring CFTR mutants. A
number of in silico tools and molecular approaches are presented. The accurate
knowledge of CFTR mutations causing or non-causing disease present obvious
interest in both clinical diagnosis and research fields. A better understanding
of the molecular defects associated with various CFTR mutations will provide a
basis for development of novel pharmacologic compounds intended to correct
transcriptional abnormalities or improve protein processing/trafficking. This is
illustrated by the functional characterization of the first sequence variation
identified in the CFTR minimal promoter, which allowed to address in original way
the important and poorly understood regulation of expression of the CFTR gene.
PMID- 17040874
TI - [Prevalence of celiac disease serological markers in Tunisian type 1 diabetic
adults].
AB - OBJECTIVE: to evaluate the prevalence of celiac serological markers; anti
transglutaminase (ATGt), anti-endomysium (AE), anti-gliadin (AGD) and anti
reticulin (AR) antibodies; in type 1 diabetic Tunisian adults. SUBJECTS AND
METHODS: 261 type 1 diabetic patients aged from 16 to 60 years were enrolled in
this prospective study. IgG and IgA transglutaminase and gliadin were measured
with ELISA. IgA AE were tested by indirect immunofluorescence using 2 substrates;
monkey oesophagus and human umbilical cord. AR were detected by indirect
immunofluorescence on rat liver, kidney and stomach. Sera IgA level was measured
by turbidimetry. RESULTS: 83/261 of diabetics were positive for at least one
antibody, 5.7% had ATGt-A, 3.4% AE on monkey esophagus, 3.1% AE on umbilical
cordon, 18% AGD-A, 19.5% AGD-G and 3.1% AR. There was an excellent concordance
between AE and ATGt (r = 0.9). Out of the 261 diabetics, 5 had an IgA deficiency
and one of them has IgG AE and ATGt. CONCLUSION: serological markers of celiac
disease seem to be frequent in diabetics. Nevertheless, diagnosis must be
confirmed by histological studies which allow us to know the real prevalence of
celiac disease in diabetic adults.
PMID- 17040875
TI - [Validation of a Bruton's disease genetic analysis method].
AB - Bruton's disease is the most frequently primary X-linked immunodeficiency.
Patients are more susceptible to early and recurring infections associated with
hypo/agammaglobulinemia and a severe B-cell deficiency. Moreover, 400 mutations
were found in the XLA gene which codes the Btk tyrosine kinase and were
identified as responsible for Bruton's disease. Genetic study was carried out
with one group of patients named NECKER, composed by five XLA patients and two
parents whose XLA gene was sequenced by an Italian crew. Results were obtained by
PCR of 19 exons and initial/terminal intron's parts, followed by PCR-sequencing
with universal primers and sequencing. The results from this study allowed the
validation of the sequencing technique by comparing NECKER group data (equivalent
results with Italian data). In addition, the mutation multiplicity (described or
not, coding/non coding) need an exact analysis that should be given to clinicians
through clear and trustful results. In this way, a strategy to analyse untreated
results was created based on the mutation type. The genetic analysis could help
physicians for uncertain diagnosis in immune defficiencies, allows proposing a
genetic advice to the patient's family and the construction of a data base
permits a best understanding of this disease.
PMID- 17040876
TI - [Significance of "anti HBC alone" serological profile in 284 patients suspicious
of being infected with hepatitis B virus].
AB - The "anti-HBc alone" serological profile is a frequent finding in hepatitis B
virus infections, but little is known about its clinical significance. The aim of
this study was to explore the 'anti-HBc alone' serological profile obtained by
immunosorbent assay (ELISA) in 284 patients suspicious of being infected with
hepatitis B virus. Sera were screened for following serological markers: HBs Ag,
anti-HBc and anti-HBs antibodies using immunoradiometric assay (IRMA) and for HBV
DNA using polymerase chain reaction. Among 284 studied sera with 'anti-HBc alone'
serological profile, 124 were positives for anti-HBs antibodies by IRMA and
corresponding to a recovered form of hepatitis B. Nineteen sera were negatives
for anti-HBc antibodies, suggesting false positive results by ELISA. Two sera
were found positives for HBs Ag by IRMA, which are related to authentic hepatitis
B. HBV DNA was positive in 4 sera, suggesting occult hepatitis B. This study
indicates that "anti-HBc alone" serological profile is most often correlates with
recovered hepatitis B infection, but it can mask an occult hepatitis B.
PMID- 17040877
TI - [Haematological characteristics, FAB and WHO classification of 153 cases of
myeloid acute leukaemia in Tunisia].
AB - A complete blood analysis with a careful morphologic examination of peripheral
blood and bone morrow smears completed by cytochemical reaction will help to
classify the most acute myeloid leukaemia (AML). Actually, the study of other
cytogenetis and immunophenotypic markers are now necessary to confirm diagnosis.
The World Health Organisation WHO classification (2001) incorporates theses
approaches. The purpose of this study is a bio-clinical review according to the
WHO recommendations in 153 cases of LAM diagnosed between January 1998 and
December 2003. The patients were aged 2 months to 90 years with sex ratio (M/F)
of 1,22. The morphologic conclusion was difficult in 12% cases. Presence of
dysplasia is noted in 50% of cases with multilineage dysplasia in 42% of cases.
Our results showed cloned chromosomal abnormalities in 57% of cases (t(8;21):
12%, t(15;17) : 10%, Inv16: 1,3%, 11q23: 2,6% et complex karyotype: 14,3%). In
69% of cases with multilineage dysplasia, the karyotype was normal. 3 cases of
LAM were noted at patients treated for breast cancer with chirurgic chemotherapy
and radiotherapy 3, 4 et 5 years after treatment (LAM3 with t(15;17), LAM4 with
genetic abnormalities of chromosomes 3, 5, 7, 8, 9, 14 et 16 et LAM 6 with
genetic abnormalities of chromosomes 4, 7, 12, 14, 19 et 21). In WHO
classification, cytology is essential in diagnosis of LAM even if the karytype
have an important prognostic value. Research of signs of dysplasia lineage after
lineage constitutes an important microscopic work and it is difficult to quantify
dysplasia when the lineage is poor.
PMID- 17040878
TI - [Simultaneous detection of IgM anti-Epstein-Barr virus and IgM anti-hepatitis A
during an acute hepatitis].
AB - We report a case of a 15-year-old young man who was admitted for an acute
hepatitis. Virological assessment showed both IgM anti-EBV and IgM anti-hepatitis
A. IgG anti-EBNA and clinical history allowed to rule out the hypothesis of a
recent EBV infection and confirmed the diagnosis of acute hepatitis A infection.
PMID- 17040879
TI - [Adaptation of methotrexate determination in plasma with Dimension Xpand].
AB - The treatment with methotrexate at high doses is responsible of many side
effects. It's necessary to evaluate serum methotrexate rate to monitor the
administration of the methotrexate antagonist, the folinic acid. The aim of this
study is to validate the determination of methotrexate in plasma using the
automate Xpand Dimension (Dade Behring). Assay results were linearly related to
the concentration for the wide range which was examinated (0.15 - 1.4
micromol/L). We report the precision, accuracy, linearity, sensitivity of this
assay. The CV was less than 10%. We present the results of correlations with Aca
(Dade Behring) and Cobas Mira (Roche). The reagent cartridge in the instrument
and the calibration are stable during 28 days.
PMID- 17040880
TI - [Non-secreting myeloma associated with nephrotic syndrome].
AB - The non-secreting myeloma is a rare form of myeloma. Its association with a
nephrotic syndrome is exceptional. The observation which we report below
described the history of a 66 years old patient who presents a non-secreting
myeloma revealed by a nephrotic syndrome. Various assumptions on the mechanism of
no excretion were put forth. Nevertheless, several points are to be elucidated as
for the pathogenesis of the association non-secreting myeloma and nephrotic
syndrome.
PMID- 17040881
TI - [Hyperhomocysteinaemia and type 2 diabetes].
AB - OBJECTIVES: Hyperhomocysteinaemia is associated with cardiovascular events in
nondiabetic individuals. The present study was aimed to explore the implication
of hyperhomocysteinemia in development of cardiovascular events in patients with
type 2 diabetes. DESIGN: A total of 185 patients with type 2 diabetes (115 women
and 70 men, 30 to 93 years of age) have been included consecutively in the
ambulatory unit at the Saint-Philibert Hospital. For each patient the
concentration of homocysteine, cholesterol and triglyceride levels and HbA1c have
been measured. In the studied population, 121 patients presented cardiovascular
events (myocardial infarctus, peripheric arteriopathy, cerebrovascular accident).
RESULTS: The patients with cardiovascular events were older, the concentration of
homocysteine and creatinine were higher. The plasma homocysteine levels adjusted
for age and creatinine levels were higher in patients with cardiovascular events
than in patients without cardiovascular events (15.4 +/- 3.52 micromol/L and
13.13 +/- 2.26 micromol/L respectively; p = 2. 10(-5)). CONCLUSIONS:
Hyperhomocysteinemia is an independant risk factor for cardiovascular events in
type 2 diabetes, independent of age and renal function.
PMID- 17040882
TI - [Incubated osmotic fragility test does not exclude red blood cell membrane
disorders! About a case of hereditary elliptocytosis].
AB - We report a case of hereditary elliptocytosis in an infant diagnosed a few months
after the birth, in a context of regenerative normocytic normochromic anaemia.
The investigations, including incubated osmotic fragility, erythrocytic enzymes
study and haemoglobin electrophoresis, were not contributive. Only the
persistence of elongated (or cigar-shaped) erythrocytes on blood smears was
noted. Hereditary elliptocytosis was confirmed by specialized investigations
(rheological study and erythrocytic membrane proteins electrophoresis).
Investigations in the mother were realized and led to the discovery of a similar
biological pattern. Hereditary elliptocytosis is a red blood cell membrane
disorder due to the defect in cytoskeleton proteins (spectrin or 4.1), leading to
the loss of deformability properties of erythrocytes. This disorder is considered
as rare; however, its incidence is probably underestimated because most cases are
pauci- or asymptomatic and the discovery is often fortuitous. The absence of
detection of this defect by incubated osmotic fragility should not discard the
hypothesis of erythrocytes membrane disorders. The persistent observation of
elongated erythrocytes on blood smear must encourage the biologist to evocate a
hereditary elliptocytosis.
PMID- 17040883
TI - [Acute polyarthritis during a parvovirus B19 primary infection].
AB - Parvovirus B19 classically causes erythema infectiosum in children, febrile
arthralgia or acute erythroblastopenia in adult. The clinical spectrum of adult
primary infection is sometimes misleading. We report an observation of an acute
rheumatoid-like arthritis following primary parvovirus B19 infection in a 42-year
old woman.
PMID- 17040884
TI - [Severe imported malaria. The experience of the military hospital of Marrakech].
AB - Incidence of severe imported malaria increases with the multiplication of
humanitarian and military missions in malarial endemic areas. The purpose of this
study was to describe the demographic, clinical, therapeutic and outcome aspects
of 9 cases which have been hospitalized in the intensive care unit and medecine
service of the military hospital of Marrakech, between january 2001 and december
2004. Out of 68 patients admitted with symptomatic malaria during this period, 9
cases were considered as severe. All of them were male soldiers (mean age: 33,3
years), 7 of them have stayed in Democratic Republic of Congo, and 2 in Ivory
Coast. Chemoprophylaxis consisted in chloroquine plus proguanil in 5 cases and
mefloquine in 4 cases. The mean duration of stay in endemic area was 9,3 months.
The clinical presentation was dominated by troubles of consciousness, which
justified initial admission in the intensive care unit. The mean duration of
hospitalization was 3,3 days in intensive care unit and 5,6 days in the medical
department. Thick smear always revealed high parasitemia (5-15%) with Plasmodium
falciparum, associated with Plasmodium ovale in two cases. Antimalarial treatment
consisted in quinine salts administration. Evolution was favourable without
recurrence in 7 cases, but 2 deaths were recorded. Severe imported malaria
remains associated with bad outcome and requires early diagnosis and close
monitoring of such cases.
PMID- 17040885
TI - [National external quality assessment in auto-immunity: auto-antibodies against
thyroid constituents].
AB - The French Health Products Safety Agency organized in 2005, for the scheme of the
national external quality assessment, a survey on antibodies against thyroid
constituents which included for the first time the quantitative assay. The
purpose of this survey was to assess the quality of the different methods of
these assays. The overall qualitative results are satisfactory. However, this
survey pointed out a lower performance for immunodot which appeared to have been
misused. Concerning the titer of antibodies, results show a broad dispersion
between reagents. This confirms the lack of a real standardisation despite of the
existence of the international MRC standards.
PMID- 17040886
TI - Does low mercury containing skin-lightening cream (fair & lovely) affect the
kidney, liver, and brain of female mice?
AB - Fair & Lovely is an over-the-counter skin-lightening cream sold widely in Saudi
markets. Its mercury content is 0.304+/-0.316 microg/g, in the range of 0.102 to
0.775 microg/g. This study was designed to evaluate its toxic effects on mice.
The cream was applied on mice for a period of 1 month at different intervals.
Mercury levels were measured in the liver, kidney, and brain tissue samples of a
total of 75 adult female CD1 mice by Atomic Absorption Spectrophotometer coupled
to a Vapor Generator Accessory. The mean mercury concentrations in the tissues of
the treated mice were 0.193+/-0.319 microg/g; whereas for the control group, it
was 0.041 microg/g+/-0.041microg/g. While the kidney was found to have the
highest mercury content, the brain was found to have the lowest content. Treated
mice showed a significant reduction in body weight. Marked histological changes
were clearly noted in the kidney and, to a lesser extent, in the brain and liver.
These results indicate that although Fair & Lovely mercury content is less than
the U.S. Food and Drug Administration (FDA) permissible limits histopathological
changes in the brain, kidney, and liver tissues are evidence of its possible
toxicity.
PMID- 17040887
TI - Correlating sensory effects with irritation.
AB - The goal of this preliminary study was to examine data collected in the course of
the development and conduct of the behind-the-knee (BTK) test for correlations
between the objective scores of erythema and the sensory effects reported by the
panelists. In addition, the intensity of physical characteristics of femcare
products and prototypes was evaluated using the descriptive analysis panel (DAP)
and results were compared to the BTK results to determine if certain physical
characteristics of the products correlated to different sensations experienced by
the BTK panelists. Test materials were commercially available or developmental
catemenial products. In the BTK test, samples were applied daily to the area
behind the knee and held in place for 6 hours per day for 5 consecutive days by
an elastic knee band of the appropriate size. Irritation was graded 30-60 minutes
after removal of each application. The DAP uses individuals trained to recognize
and grade certain physical characteristics of products, including degree of
plastic feel, scratchiness, glide, and cottony feel. In the BTK studies, the
ability to differentiate between the test samples via reported sensory effects
correlated with the ability to differentiate via objective scores for irritation
in seven of 15 comparisons. A correlation between the magnitude of the irritation
score, independent of the specific test sample, and reports of adverse sensory
effects was observed in 13 of 15 comparisons. Two comparisons conducted in the
BTK were also evaluated using the DAP. For one comparison, there was a clear
difference in the product physical characteristics in the DAP that was consistent
with mean erythema scores and reported sensory effects in the BTK. For the other
comparison, there was no clear difference between the two products by either the
DAP or the BTK.
PMID- 17040888
TI - Comparative cytotoxicity potential of soft contact lens care products.
AB - PURPOSE: To determine the cytotoxicity potential of soft contact lens care
products and benzalkonium chloride (BAK) by two colorimetric in vitro assays on
an immortalized human corneal epithelial cell line (HCE-T). METHODS: Four
commercial soft contact lens care solutions were tested at 1:3 dilution in growth
medium. The positive controls for cytotoxicity were BAK in Dulbecco's phosphate
buffered saline (DPBS) at 10, 5, 2.5, and 1.25 ppm and 1:3 dilution of DPBS as
negative control. Cell viability was assayed using a novel tetrazolium compound
and an electron coupling reagent (MTS/PES), and by cell membrane integrity using
neutral red dye uptake and release (NRUR). Mean spectrophotometric optical
density of the test samples was compared to mean optical density of the controls
at 24 and 48 hours of exposure to test product. Significance was measured by
ANOVA/Tukey HSD test. RESULTS: Cell viability and cell membrane integrity tests
were not significantly different between lens care solutions and the negative
controls for CIBA Vision SOLOcare PLUS, Advanced Medical Optics COMPLETE Comfort
PLUS, or BAK at 1.25 ppm. Exposure to Bausch and Lomb ReNu MultiPlus, Alcon OPTI
FREE Express with Aldox, BAK 10, 5, and 2.5 ppm yielded significant reduction in
cell viability and membrane integrity compared to negative controls. DISCUSSION:
Assays of HCE-T cell viability by MTS/PES, and cell membrane integrity by NRUR
cells yielded data that were similar to that previously reported with mouse L929
cells in tests based on the USP Elution Test. For the MTS/PES and NRUR assay
methods, the solutions in order of increasing cytotoxicity potential were:
SOLOCare = COMPLETE Comfort Plus < ReNu < < OPTI-FREE Express with Aldox.
PMID- 17040889
TI - Preparation and characterization of demeclocycline liposomal formulations and
assessment of their intraocular pressure-lowering effects.
AB - The objective of the present study is to enhance the ocular permeability and to
study the ocular disposition of demeclocycline (DEM), liposomal topical
formulation for treatment of elevated intraocular pressure using Male New Zealand
albino rabbits as an animal model. METHODS: Different liposomal formulations of
the DEM were prepared and characterized for their drug entrapment, drug-liposome
affinity and the in vivo distribution of DEM in various ocular tissues. Liposomal
formulations of promising drug distribution within the various ocular tissues
have been scaled up for the in vivo intraocular pressure (IOP) measurements by
Pneuma-tonometer using different dosing regimens. RESULTS: The amounts of drug
entrapped in the charged liposomal formulations were comparable and lower than
that entrapped with neutral ones. DEM was found to be more concentrated (69-95%)
in the lipid phase of the liposome. The concentrations of DEM in the cornea,
aqueous humor, and conjunctiva were 4.76, 2.18, and 23.32 microg/g of tissue,
respectively. Test formulations have shown significant reductions in the IOP on
using different treatment protocols. CONCLUSION: Preparation of liposomal
formulations of DEM has substantially enhanced its transcorneal transport.
Furthermore, the test formulations have shown promising and long-lasting
intraocular pressure-lowering effect comparable with that of pilocarpine
formulation as a control.
PMID- 17040890
TI - The vulva is relatively insensitive to menses-induced irritation.
AB - Skin patch testing of menses and venous blood on the vulva (labia majora) and the
upper arm was performed to assess the potential contribution of these biological
fluids to vulvar irritation during menstruation. After 24 and 48 hours of
occlusive exposure, the skin of the labia majora was relatively unaffected by
these fluids compared to the skin of the upper arm: no significant irritation was
observed on the labia at either exposure time, but discernible irritation was
elicited on the upper arm after 48 hours of exposure. Pre-treatment of the upper
arm with a petrolatum-based emollient attenuated the upper arm response. Semi
occlusive conditions also reduced the degree of upper-arm irritation elicited
test materials and an irritant control, sodium lauryl sulfate. The relative
insensitivity of the vulva to irritation by menses or blood was not predictable a
priori because some irritants elicit heightened responses on the vulva relative
to the arm (3). These results suggest that the vulva (labia majora) may be
adapted to be less sensitive to menses-induced skin irritation than other
anatomical sites.
PMID- 17040892
TI - UK consultant rheumatologists' access to biological agents and views on the BSR
Biologics Register.
AB - OBJECTIVES: The British Society for Rheumatology Biologics Register (BSRBR) is a
prospective cohort study to determine the efficacy and toxicity of biological
agents in rheumatoid arthritis (RA) patients compared with RA controls. Entry of
patients to the register is a condition of use of anti-tumour necrosis factor
(anti-TNF) therapy in the UK, but little is known of clinicians' views of its
usefulness. Data from the register suggest uneven provision of anti-TNF-alpha
therapy. METHODS: A questionnaire was sent on behalf of the BSRBR to all UK
consultant rheumatologists concerning provision and use of anti-TNF-alpha therapy
and their experience of working with the BSRBR. RESULTS: Response rate was 49.5%
representing 252 consultants. Fourty-six per cent had some limitation of access
to anti-TNF-alpha drugs, usually a financial cap (70%), even for RA patients
meeting National Institute for Health and Clinical Excellence (NICE) criteria.
Sixty-seven per cent could prescribe for ankylosing spondylitis (AS) or psoriatic
arthritis (PsA) in some circumstances but only 25 and 35%, respectively, could
prescribe according to BSR guidance. More than 50% found the workload involved in
submitting data to the registry at least difficult, but most had favourable
impressions of the BSRBR and thought similar registries desirable or essential
for PsA, AS and rituximab. CONCLUSIONS: Access to anti-TNF therapy for patients
with inflammatory arthritis is variable in the UK, even for RA where it is NICE
approved. Access is more limited for conditions where NICE has not yet issued
guidance. The BSRBR generates a significant workload for rheumatology staff but
is generally well-regarded.
PMID- 17040893
TI - Characterization of a nucleocapsid-like region and of two distinct primer
tRNALys,2 binding sites in the endogenous retrovirus Gypsy.
AB - Mobile LTR-retroelements comprising retroviruses and LTR-retrotransposons form a
large part of eukaryotic genomes. Their mode of replication and abundance favour
the notion that they are major actors in eukaryote evolution. The Gypsy
retroelement can spread in the germ line of the fruit fly Drosophila melanogaster
via both env-independent and env-dependent processes. Thus, Gypsy is both an
active retrotransposon and an infectious retrovirus resembling the
gammaretrovirus MuLV. However, unlike gammaretroviruses, the Gypsy Gag structural
precursor is not processed into Matrix, Capsid and Nucleocapsid (NC) proteins. In
contrast, it has features in common with Gag of the ancient yeast TY1
retroelement. These characteristics of Gypsy make it a very interesting model to
study replication of a retroelement at the frontier between ancient
retrotransposons and retroviruses. We investigated Gypsy replication using an in
vitro model system and transfection of insect cells. Results show that an
unstructured domain of Gypsy Gag has all the properties of a retroviral NC. This
NC-like peptide forms ribonucleoparticle-like complexes upon binding Gypsy RNA
and directs the annealing of primer tRNA(Lys,2) to two distinct primer binding
sites (PBS) at the genome 5' and 3' ends. Only the 5' PBS is indispensable for
cDNA synthesis in vitro and in Drosophila cells.
PMID- 17040894
TI - Identification of insertion hot spots for non-LTR retrotransposons: computational
and biochemical application to Entamoeba histolytica.
AB - The genome of the human pathogen Entamoeba histolytica contains non-long terminal
repeat (LTR) retrotransposons, the EhLINEs and EhSINEs, which lack targeted
insertion. We investigated the importance of local DNA structure, and sequence
preference of the element-encoded endonuclease (EN) in selecting target sites for
retrotransposon insertion. Pre-insertion loci were tested computationally to
detect unique features based on DNA structure, thermodynamic considerations and
protein interaction measures. Target sites could readily be distinguished from
other genomic sites based on these criteria. The contribution of the EhLINE1
encoded EN in target site selection was investigated biochemically. The sequence
specificity of the EN was tested in vitro with a variety of mutated substrates.
It was possible to assign a consensus sequence, 5'-GCATT-3', which was
efficiently nicked between A-T and T-T. The upstream G residue enhanced EN
activity, possibly serving to limit retrotransposition in the A+T-rich
E.histolytica genome. Mutated substrates with poor EN activity showed structural
differences compared with normal substrates. Analysis of retrotransposon
insertion sites from a variety of organisms showed that, in general, regions of
favorable DNA structure were recognized for retrotransposition. A combination of
favorable DNA structure and preferred EN nicking sequence in the vicinity of this
structure may determine the genomic hotspots for retrotransposition.
PMID- 17040895
TI - Fluorescent T7 display phages obtained by translational frameshift.
AB - Lytic phages form a powerful platform for the display of large cDNA libraries and
offer the possibility to screen for interactions with almost any substrate. To
visualize these interactions directly by fluorescence microscopy, we constructed
fluorescent T7 phages by exploiting the flexibility of phages to incorporate
modified versions of its capsid protein. By applying translational frameshift
sequences, helper plasmids were constructed that expressed a fixed ratio of both
wild-type capsid protein (gp10) and capsid protein fused to enhanced yellow
fluorescent protein (EYFP). The frameshift sequences were inserted between the 3'
end of the capsid gene and the sequence encoding EYFP. Fluorescent fusion
proteins are only formed when the ribosome makes a -1 shift in reading frame
during translation. Using standard fluorescence microscopy, we could sensitively
monitor the enrichment of specific binders in a cDNA library displayed on
fluorescent T7 phages. The perspectives of fluorescent display phages in the fast
emerging field of single molecule detection and sorting technologies are
discussed.
PMID- 17040896
TI - ATM mediates oxidative stress-induced dephosphorylation of DNA ligase IIIalpha.
AB - Among the three mammalian genes encoding DNA ligases, only the LIG3 gene does not
have a homolog in lower eukaryotes. In somatic mammalian cells, the nuclear form
of DNA ligase IIIalpha forms a stable complex with the DNA repair protein XRCC1
that is also found only in higher eukaryotes. Recent studies have shown that
XRCC1 participates in S phase-specific DNA repair pathways independently of DNA
ligase IIIalpha and is constitutively phosphorylated by casein kinase II. In this
study we demonstrate that DNA ligase IIIalpha, unlike XRCC1, is phosphorylated in
a cell cycle-dependent manner. Specifically, DNA ligase IIIalpha is
phosphorylated on Ser123 by the cell division cycle kinase Cdk2 beginning early
in S phase and continuing into M phase. Interestingly, treatment of S phase cells
with agents that cause oxygen free radicals induces the dephosphorylation of DNA
ligase IIIalpha. This oxidative stress-induced dephosphorylation of DNA ligase
IIIalpha is dependent upon the ATM (ataxia-telangiectasia mutated) kinase and
appears to involve inhibition of Cdk2 and probably activation of a phosphatase.
PMID- 17040897
TI - Beta-Catenin stabilizes cyclooxygenase-2 mRNA by interacting with AU-rich
elements of 3'-UTR.
AB - Cyclooxygenase-2 (COX-2) mRNA is induced in the majority of human colorectal
carcinomas. Transcriptional regulation plays a key role in COX-2 expression in
human colon carcinoma cells, but post-transcriptional regulation of its mRNA is
also critical for tumorigenesis. Expression of COX-2 mRNA is regulated by various
cytokines, growth factors and other signals. beta-Catenin, a key transcription
factor in the Wnt signal pathway, activates transcription of COX-2. Here we found
that COX-2 mRNA was also substantially stabilized by activating beta-catenin in
NIH3T3 and 293T cells. We identified the beta-catenin-responsive element in the
proximal region of the COX-2 3'-untranslated region (3'-UTR) and showed that beta
catenin interacted with AU-rich elements (ARE) of 3'-UTR in vitro and in vivo.
Interestingly, beta-catenin induced the cytoplasmic localization of the RNA
stabilizing factor, HuR, which may bind to beta-catenin in an RNA-mediated
complex and facilitate beta-catenin-dependent stabilization of COX-2 mRNA. Taken
together, we provided evidences for beta-catenin as an RNA-binding factor and a
regulator of stabilization of COX-2 mRNA.
PMID- 17040898
TI - The majority of Escherichia coli mRNAs undergo post-transcriptional modification
in exponentially growing cells.
AB - Polyadenylation of RNAs by poly(A) polymerase I (PAP I) in Escherichia coli plays
a significant role in mRNA decay and general RNA quality control. However, many
important features of this system, including the prevalence of polyadenylated
mRNAs in the bacterium, are still poorly understood. By comparing the
transcriptomes of wild-type and pcnB deletion strains using macroarray analysis,
we demonstrate that >90% of E.coli open reading frames (ORFs) transcribed during
exponential growth undergo some degree of polyadenylation by PAP I, either as
full-length transcripts or decay intermediates. Detailed analysis of over 240
transcripts suggests that Rho-independent transcription terminators serve as
polyadenylation signals. Conversely, mRNAs terminated in a Rho-dependent fashion
are probably not substrates for PAP I, but can be modified by the addition of
long polynucleotide tails through the biosynthetic activity of polynucleotide
phosphorylase (PNPase). Furthermore, real-time PCR analysis indicates that the
extent of polyadenylation of individual full-length transcripts such as lpp and
ompA varies significantly in wild-type cells. The data presented here
demonstrates that polyadenylation in E.coli occurs much more frequently than
previously envisioned.
PMID- 17040899
TI - Different loop arrangements of intramolecular human telomeric (3+1) G
quadruplexes in K+ solution.
AB - Intramolecular G-quadruplexes formed by the human telomeric G-rich strand are
promising anticancer targets. Here we show that four-repeat human telomeric DNA
sequences can adopt two different intramolecular G-quadruplex folds in K+
solution. The two structures contain the (3+1) G-tetrad core, in which three G
tracts are oriented in one direction and the fourth in the opposite direction,
with one double-chain-reversal and two edgewise loops, but involve different loop
arrangements. This result indicates the robustness of the (3+1) core G-quadruplex
topology, thereby suggesting it as an important platform for structure-based drug
design. Our data also support the view that multiple human telomeric G-quadruplex
conformations coexist in K+ solution. Furthermore, even small changes to flanking
sequences can perturb the equilibrium between different coexisting G-quadruplex
forms.
PMID- 17040900
TI - Chondroitin 4-O-sulfotransferase-1 regulates E disaccharide expression of
chondroitin sulfate required for herpes simplex virus infectivity.
AB - We have demonstrated a defect in expression of chondroitin 4-O-sulfotransferase-1
(C4ST-1) in murine sog9 cells, which are poorly sensitive to infection by herpes
simplex virus type 1 (HSV-1). Sog9 cells were previously isolated as CS-deficient
cells from gro2C cells, which were partially resistant to HSV-1 infection and
defective in the expression of heparan sulfate (HS) because of a splice site
mutation in the EXT1 gene encoding the HS-synthesizing enzyme. Here we detected a
small amount of CS chains in sog9 cells with a drastic decrease in 4-O-sulfation
compared with the parental gro2C cells. RT-PCR revealed that sog9 cells had a
defect in the expression of C4ST-1 in addition to EXT1. Gel filtration analysis
showed that the decrease in the amount of CS in sog9 cells was the result of a
reduction in the length of CS chains. Transfer of C4ST-1 cDNA into sog9 cells
(sog9-C4ST-1) restored 4-O-sulfation and amount of CS, verifying that sog9 cells
had a specific defect in C4ST-1. Furthermore, the expression of C4ST-1 rendered
sog9 cells significantly more susceptible to HSV-1 infection, suggesting that CS
modified by C4ST-1 is sufficient for the binding and infectivity of HSV-1.
Analysis of CS chains of gro2C and sog9-C4ST-1 cells revealed a considerable
proportion of the E disaccharide unit, consistent with our recent finding that
this unit is an essential component of the HSV receptor. These results suggest
that C4ST-1 regulates the expression of the E disaccharide unit and the length of
CS chains, the features that facilitate infection of cells by HSV-1.
PMID- 17040901
TI - Hemoglobin-degrading plasmepsin II is active as a monomer.
AB - A family of aspartic proteases called plasmepsins is important for hemoglobin
degradation in intraerythrocytic Plasmodium parasites. Plasmepsin II (PM II) is
the best studied member of this family. PM II and its close orthologs and
paralogs form homodimers with extensive interfaces in all known crystal
structures. This raised the question whether the homodimer is the functional
subunit of plasmepsins in solution. We have used gel filtration chromatography,
site-directed mutagenesis, and analytical ultracentrifugation to study the
oligomeric status of PM II in solution. Our results reveal that PM II exists
mainly as a monomer in solution and that the monomer is fully functional for
catalysis. A hydrophobic loop at the PM II monomer surface, which would be buried
in a PM II dimer, is shown to be essential for the hemoglobin degradation
capability of PM II.
PMID- 17040902
TI - Induction of the heat shock pathway during hypoxia requires regulation of heat
shock factor by hypoxia-inducible factor-1.
AB - Activation of heat shock proteins (Hsps) is critical to adaptation to low oxygen
levels (hypoxia) and for enduring the oxidative stress of reoxygenation. Hsps are
known to be regulated by heat shock factor (Hsf), but our results demonstrate an
unexpected regulatory link between the oxygen-sensing and heat shock pathways.
Hsf transcription is up-regulated during hypoxia due to direct binding by hypoxia
inducible factor-1 (HIF-1) to HIF-1 response elements in an Hsf intron. This
increase in Hsf transcripts is necessary for full Hsp induction during hypoxia
and reoxygenation. The HIF-1-dependent increase in Hsps has a functional impact,
as reduced production of Hsps decreases viability of adult flies exposed to
hypoxia and reoxygenation. Thus, HIF-1 control of Hsf transcriptional levels is a
regulatory mechanism for sensitizing heat shock pathway activity in order to
maximize production of protective Hsps. This cross-regulation represents a
mechanism by which the low oxygen response pathway has assimilated complex new
functions by regulating the key transcriptional activator of the heat shock
pathway.
PMID- 17040903
TI - Trypanosoma seryl-tRNA synthetase is a metazoan-like enzyme with high affinity
for tRNASec.
AB - Trypanosomatids are important human pathogens that form a basal branch of
eukaryotes. Their evolutionary history is still unclear as are many aspects of
their molecular biology. Here we characterize essential components required for
the incorporation of serine and selenocysteine into the proteome of Trypanosoma.
First, the biological function of a putative Trypanosoma seryl-tRNA synthetase
was characterized in vivo. Secondly, the molecular recognition by Trypanosoma
seryl-tRNA synthetase of its cognate tRNAs was dissected in vitro. The cellular
distribution of tRNA(Sec) was studied, and the catalytic constants of its
aminoacylation were determined. These were found to be markedly different from
those reported in other organisms, indicating that this reaction is particularly
efficient in trypanosomatids. Our functional data were analyzed in the context of
a new phylogenetic analysis of eukaryotic seryl-tRNA synthetases that includes
Trypanosoma and Leishmania sequences. Our results show that trypanosomatid seryl
tRNA synthetases are functionally and evolutionarily more closely related to
their metazoan homologous enzymes than to other eukaryotic enzymes. This
conclusion is supported by sequence synapomorphies that clearly connect metazoan
and trypanosomatid seryl-tRNA synthetases.
PMID- 17040904
TI - Molecular mechanisms of import of peroxisome-targeting signal type 2 (PTS2)
proteins by PTS2 receptor Pex7p and PTS1 receptor Pex5pL.
AB - In the present study, we investigated molecular mechanisms underlying the import
of peroxisome-targeting signal type 2 (PTS2) proteins into peroxisomes. Purified
Chinese hamster Pex7p that had been expressed in an Sf9/baculovirus system was
biologically active in several assays such as those for PTS2 binding and
assessing the restoration of the impaired PTS2 protein import in Chinese hamster
ovary (CHO) pex7 mutant ZPG207. Pex7p was eluted as a monomer in gel filtration
chromatography. Moreover, the mutation of the highly conserved cysteine residue
suggested to be involved in the dimer formation did not affect the complementing
activity in ZPG207 cells. Together, Pex7p more likely functions as a monomer.
Together with PTS1 protein, the Pex7p-PTS2 protein complex was bound to Pex5pL,
the longer form of Pex5p, which was prerequisite for the translocation of Pex7p
PTS2 protein complexes. Pex5pL-(Pex7p-PTS2 protein) complexes were detectable in
wild-type CHO-K1 cells and were apparently more stable in pex14 CHO cells
deficient in the entry site of the matrix proteins, whereas only the Pex7p-PTS2
protein complex was discernible in a Pex5pL-defective pex5 CHO mutant. Pex7p-PTS2
proteins bound to Pex14p via Pex5pL. In contrast, PTS2 protein-bound Pex7p as
well as Pex7p directly and equally interacted with Pex13p, implying that the PTS2
cargo may be released at Pex13p. Furthermore, we detected the Pex13p complexes
likewise formed with Pex5pL-bound Pex7p-PTS2 proteins. Thus, the Pex7p-mediated
PTS2 protein import shares most of the steps with the Pex5p-dependent PTS1 import
machinery but is likely distinct at the cargo-releasing stage.
PMID- 17040905
TI - The functional effects of physical interactions among Toll-like receptors 7, 8,
and 9.
AB - Toll-like receptors (TLRs) TLR1, TLR2, TLR4, and TLR6 are evolutionarily
conserved, highly homologous, and localized to plasma membranes of host cells and
recognize pathogen-associated molecular patterns (PAMPs) derived from bacterial
membranes. These receptors cooperate in a pairwise combination to elicit or
inhibit the inflammatory signals in response to certain PAMPs. The other TLRs
that are evolutionarily closely related and highly homologous are TLR7, TLR8, and
TLR9. They are all confined to the membranes of endosomes and recognize similar
molecular structures, the oligonucleotide-based PAMPs. However, the cooperative
interactions among these receptors that may modulate the inflammatory signaling
in response to their cognate agonists are not reported. We report here for the
first time the functional effects of one TLR on the other among TLR7, TLR8, and
TLR9. The results indicate that TLR8 inhibits TLR7 and TLR9, and TLR9 inhibits
TLR7 but not vice versa in HEK293 cells transfected with TLRs in a pairwise
combination. This is concluded by selectively activating one TLR over the other
by using small molecule TLR agonists. We also show that these inhibitory
interactions are the result of direct or indirect physical interactions between
the TLRs. The murine TLR8 that does not respond to any known human TLR8 agonists
also inhibits both murine and human TLR7. The implications of the inhibitory
interactions among these TLRs in host-pathogen recognition and subsequent
inflammatory responses are not obvious. However, given the complexity in
expression pattern in a particular cell type and the variation in distribution
and response to different pathogens and stress signals in different cell types,
the inhibitory physical interactions among these TLRs may play a role in
balancing the inflammatory outcome from a given cell type to a specific
challenge.
PMID- 17040906
TI - Mitochondrial production of reactive oxygen species mediate dicumarol-induced
cytotoxicity in cancer cells.
AB - Dicumarol is a naturally occurring anticoagulant derived from coumarin that
induces cytotoxicity and oxidative stress in human pancreatic cancer cells
(Cullen, J. J., Hinkhouse, M. M., Grady, M., Gaut, A. W., Liu, J., Zhang, Y.,
Weydert, C. J. D., Domann, F. E., and Oberley, L. W. (2003) Cancer Res. 63, 5513
5520). Although dicumarol has been used as an inhibitor of the two-electron
reductase NAD(P)H:quinone oxidoreductase (NQO1), dicumarol is also thought to
affect quinone-mediated electron transfer reactions in the mitochondria, leading
to the production of superoxide (O2*-) and hydrogen peroxide (H(2)O(2)). We
hypothesized that mitochondrial production of reactive oxygen species mediates
the increased susceptibility of pancreatic cancer cells to dicumarol-induced
metabolic oxidative stress. Dicumarol decreased clonogenic survival equally in
both MDA-MB-468 NQO1(-) and MDA-MB-468 NQO1+ breast cancer cells. Dicumarol
decreased clonogenic survival in the transformed fibroblast cell line IMRSV-90
compared with the IMR-90 cell line. Dicumarol, with the addition of mitochondrial
electron transport chain blockers, decreased clonogenic cell survival in human
pancreatic cancer cells and increased superoxide levels. Dicumarol with the
mitochondrial electron transport chain blocker antimycin A decreased clonogenic
survival and increased superoxide levels in cells with functional mitochondria
but had little effect on cancer cells without functional mitochondria.
Overexpression of manganese superoxide dismutase and mitochondrial-targeted
catalase with adenoviral vectors reversed the dicumarol-induced cytotoxicity and
reversed fluorescence of the oxidation-sensitive probe. We conclude mitochondrial
production of reactive oxygen species mediates the increased susceptibility of
cancer cells to dicumarol-induced cytotoxicity.
PMID- 17040907
TI - Antiangiogenic antithrombin blocks the heparan sulfate-dependent binding of
proangiogenic growth factors to their endothelial cell receptors: evidence for
differential binding of antiangiogenic and anticoagulant forms of antithrombin to
proangiogenic heparan sulfate domains.
AB - The anticoagulant serpin antithrombin acquires a potent antiangiogenic activity
upon undergoing conformational alterations to cleaved or latent forms. Here we
show that antithrombin antiangiogenic activity is mediated at least in part
through the ability of the conformationally altered serpin to block the
proangiogenic growth factors fibroblast growth factor (FGF)-2 and vascular
endothelial growth factor (VEGF) from forming signaling competent ternary
complexes with their protein receptors and heparan sulfate co-receptors on
endothelial cells. Cleaved and latent but not native forms of antithrombin
blocked the formation of FGF-2-FGF receptor-1 ectodomain-heparin ternary
complexes, and the dimerization of these complexes in solution and similarly
inhibited the formation of FGF-2-heparin binary complexes and their dimerization.
Only antiangiogenic forms of antithrombin likewise inhibited (125)I-FGF-2 binding
to its low affinity heparan sulfate co-receptor and blocked FGF receptor-1
autophosphorylation and p42/44 MAP kinase phosphorylation in cultured human
umbilical vein endothelial cells (HUVECs). Moreover, treatment of HUVECs with
heparinase III to specifically eliminate the FGF-2 heparan sulfate co-receptor
suppressed the ability of antiangiogenic antithrombin to inhibit growth factor
stimulated proliferation. Antiangiogenic antithrombin inhibited full-length
VEGF(165) stimulation of HUVEC proliferation but did not affect the stimulation
of cells by the heparin-binding domain-deleted VEGF(121). Taken together, these
results demonstrate that antiangiogenic forms of antithrombin block the
proangiogenic effects of FGF-2 and VEGF on endothelial cells by competing with
the growth factors for binding the heparan sulfate co-receptor, which mediates
growth factor-receptor interactions. Moreover, the inability of native
antithrombin to bind this co-receptor implies that native and conformationally
altered forms of antithrombin differentially bind proangiogenic heparan sulfate
domains.
PMID- 17040908
TI - The cysteine-rich domain of snake venom metalloproteinases is a ligand for von
Willebrand factor A domains: role in substrate targeting.
AB - Snake venom metalloproteinases (SVMPs) are members of the Reprolysin family of
metalloproteinases to which the ADAM (a disintegrin and metalloproteinase)
proteins also belong. The disintegrin-like/cysteine-rich domains of the ADAMs
have been implicated in their function. In the case of the SVMPs, we hypothesized
that these domains could function to target the metalloproteinases to key
extracellular matrix proteins or cell surface proteins. Initially we detected
interaction of collagen XIV, a fibril-associated collagen with interrupted triple
helices containing von Willebrand factor A (VWA) domains, with the PIII SVMP
catrocollastatin. Next we investigated whether other VWA domain-containing matrix
proteins could support the binding of PIII SVMPs. Using surface plasmon
resonance, the PIII SVMP jararhagin and a recombinant cysteine-rich domain from a
PIII SVMP were demonstrated to bind to collagen XIV, collagen XII, and matrilins
1, 3, and 4. Jararhagin was shown to cleave these proteins predominantly at sites
localized at or near the VWA domains suggesting that it is the VWA domains to
which the PIII SVMPs are binding via their cysteine-rich domain. In light of the
fact that these extracellular matrix proteins function to stabilize matrix,
targeting the SVMPs to these proteins followed by their specific cleavage could
promote the destabilization of extracellular matrix and cell-matrix interactions
and in the case of capillaries could contribute to their disruption and
hemorrhage. Although there is only limited structural homology shared by the
cysteine-rich domains of the PIII SVMPs and the ADAMs our results suggest an
analogous function for the cysteine-rich domains in certain members of the
expanded ADAM family of proteins to target them to VWA domain-containing
proteins.
PMID- 17040909
TI - TorT, a member of a new periplasmic binding protein family, triggers induction of
the Tor respiratory system upon trimethylamine N-oxide electron-acceptor binding
in Escherichia coli.
AB - In anaerobiosis, Escherichia coli can use trimethylamine N-oxide (TMAO) as a
terminal electron acceptor. Reduction of TMAO in trimethylamine (TMA) is mainly
performed by the respiratory TMAO reductase. This system is encoded by the torCAD
operon, which is induced in the presence of TMAO. This regulation involves a two
component system comprising TorS, an unorthodox histidine kinase, and TorR, a
response regulator. A third protein, TorT, sharing homologies with periplasmic
binding proteins, plays a key role in this regulation because disruption of the
torT gene abolishes tor expression. In this study we showed that TMAO protects
TorT against degradation by the GluC endoproteinase and modifies its temperature
induced CD spectrum. We also isolated a TorT negative mutant that is no longer
protected by TMAO from degradation by GluC. Isothermal titration calorimetry
confirmed that TorT binds TMAO with a binding constant of 150 mum. Therefore, we
conclude that TorT binds TMAO and that this binding promotes a conformational
change of TorT. We also showed that TorT interacts with the periplasmic domain of
TorS in both the presence and absence of TMAO but the TorT-TMAO complex induces a
higher GluC protection of TorS than TorT alone. These results support the idea
that TMAO binding to TorT induces a cascade of conformational changes from TorT
to TorS, leading to TorS activation. We identified several homologues of the TorT
protein that define a new family of periplasmic binding proteins. We thus propose
that the members of this family bind TMAO or related compounds and that they are
involved in signal transduction or even substrate transport.
PMID- 17040910
TI - Investigation of the dimer interface and substrate specificity of prolyl
dipeptidase DPP8.
AB - DPP8 belongs to the family of prolyl dipeptidases, which are capable of cleaving
the peptide bond after a penultimate proline residue. Unlike DPP-IV, a drug
target for type II diabetes, no information is available on the crystal structure
of DPP8, the regulation of its enzymatic activity, or its substrate specificity.
In this study, using analytical ultracentrifugation and native gel
electrophoresis, we show that the DPP8 protein is predominantly dimeric when
purified or in the cell extracts. Four conserved residues in the C-terminal loop
of DPP8 (Phe(822), Val(833), Tyr(844), and His(859)), corresponding to those
located at the dimer interface of DPP-IV, were individually mutated to Ala.
Surprisingly, unlike DPP-IV, these single-site mutations abolished the enzymatic
activity of DPP8 without disrupting its quaternary structure, indicating that
dimerization itself is not sufficient for the optimal enzymatic activity of DPP8.
Moreover, these mutations not only decreased k(cat), as did the corresponding DPP
IV mutations, but also dramatically increased K(m). We further show that the K(m)
effect is independent of the substrate assayed. Finally, we identified the
distinctive and strict substrate selectivity of DPP8 for hydrophobic or basic
residues at the P2 site, which is in sharp contrast to the much less
discriminative substrate specificity of DPP-IV. Our study has identified the
residues absolutely required for the optimal activity of DPP8 and its unique
substrate specificity. This study extends the functional importance of the C
terminal loop to the whole family of prolyl dipeptidases.
PMID- 17040911
TI - Protease domain glycans affect oligomerization, disulfide bond formation, and
stability of the meprin A metalloprotease homo-oligomer.
AB - The meprin A homo-oligomer is a highly glycosylated, secreted zinc
metalloprotease of the astacin family and metzincin superfamily. This isoform of
meprin is composed of disulfide-bonded dimers of alpha subunits that further
associate to form large, secreted megadalton complexes of 10 or more subunits.
The aim of this study was to determine the sites of glycan attachment and to
assess their ability to affect the formation and stability of the homo-oligomer.
Nine of the ten potential N-linked glycosylation sites (Asn-41, Asn-152, Asn-234,
Asn-270, Asn-330, Asn-426, Asn-452, Asn-546, and Asn-553) were found to be
glycosylated in recombinant mouse meprin A using chemical and enzymatic
deglycosylation methods and electrospray ionization mass spectrometry. Chemical
cross-linking demonstrated that carbohydrates are at or near the noncovalent
subunit interface. The removal of two glycans in the protease domain at Asn-234
and Asn-270, as well as one in the tumor necrosis factor receptor-associated
factor domain at Asn-452, by a deglycosidase under nondenaturing conditions
decreased the chemical and thermal stability of the homo-oligomer without
affecting quaternary structure. Site-directed mutagenesis demonstrated that no
single glycan was essential for oligomer formation; however, the combined absence
of the glycans at Asn-152 and Asn-270 in the protease domain hindered
intersubunit disulfide bond formation, prevented noncovalent associations, and
abolished enzymatic activity. These studies provide insights into the role of
glycans in the biosynthesis, activity, and stability of this extracellular
protease.
PMID- 17040912
TI - A new class of signal transducer in His-Asp phosphorelay systems.
AB - Nitrate transport activity of the LtnT permease of the cyanobacterium
Synechococcus elongatus is activated when LtnA, a response regulator without an
effector domain, is phosphorylated by LtnB, a hybrid histidine kinase. We
identified a protein (LtnC) that is required for activation of LtnT. LtnC
consists of an N-terminal histidine-containing phosphoacceptor (HisKA) domain, a
receiver domain, and a unique C-terminal domain found in some cyanobacterial
proteins. Because LtnC lacks an ATP-binding kinase domain of a histidine kinase,
it is incapable of autophosphorylation, but LtnC is phosphorylated by LtnA. The
histidine residue in the HisKA domain but not the aspartate residue in the
receiver domain is essential for phosphorylation of LtnC and activation of LtnT.
LtnC phosphorylation leads to oligomerization of the protein. Fusion of the C
terminal domain of LtnC to glutathione S-transferase, which forms oligomers, also
activates LtnT, suggesting that oligomerization of the LtnC C-terminal domain
causes LtnT activation. These results indicate that the C-terminal domain of LtnC
acts as an effector domain that directs the output of the signal from the
phosphorelay system. The two-step (His-Asp-His) phosphorelay system, composed of
the LtnB, LtnA, and LtnC proteins, is distinct from the known phosphorelay
systems, namely, the typical two-component system (His-Asp) and the multistep
phosphorelay system (His-Asp-His-Asp), because the HisKA domain of LtnC is the
terminal phosphoacceptor that determines the signal output. LtnC is a new class
of signal transducer in His-Asp phosphorelay systems that contains a HisKA domain
and an effector domain.
PMID- 17040913
TI - An unusual twin-his arrangement in the pore of ammonia channels is essential for
substrate conductance.
AB - Amt proteins constitute a class of ubiquitous integral membrane proteins that
mediate movement of ammonium across cell membranes. They are homotrimers, in
which each subunit contains a narrow pore through which substrate transport
occurs. Two conserved histidine residues in the pore have been proposed to be
necessary for ammonia conductance. By analyzing 14 engineered polar and non-polar
variants of these histidines, in Escherichia coli AmtB, we show that both
histidines are absolutely required for optimum substrate conductance. Crystal
structures of variants confirm that substitution of the histidine residues does
not affect AmtB structure. In a subgroup of Amt proteins, found only in fungi,
one of the histidines is replaced by glutamate. The equivalent substitution in E.
coli AmtB is partially active, and the structure of this variant suggests that
the glutamate side chain can make similar interactions to those made by
histidine.
PMID- 17040914
TI - Molecular determinants for G protein betagamma modulation of ionotropic glycine
receptors.
AB - The ligand-gated ion channel superfamily plays a critical role in neuronal
excitability. The functions of glycine receptor (GlyR) and nicotinic
acetylcholine receptor are modulated by G protein betagamma subunits. The
molecular determinants for this functional modulation, however, are still
unknown. Studying mutant receptors, we identified two basic amino acid motifs
within the large intracellular loop of the GlyR alpha(1) subunit that are
critical for binding and functional modulation by Gbetagamma. Mutations within
these sequences demonstrated that all of the residues detected are important for
Gbetagamma modulation, although both motifs are necessary for full binding.
Molecular modeling predicts that these sites are alpha-helixes near transmembrane
domains 3 and 4, near to the lipid bilayer and highly electropositive. Our
results demonstrate for the first time the sites for G protein betagamma subunit
modulation on GlyRs and provide a new framework regarding the ligand-gated ion
channel superfamily regulation by intracellular signaling.
PMID- 17040915
TI - The DNA binding preference of RAD52 and RAD59 proteins: implications for RAD52
and RAD59 protein function in homologous recombination.
AB - We examined the double-stranded DNA (dsDNA) binding preference of the
Saccharomyces cerevisiae Rad52 protein and its homologue, the Rad59 protein. In
nuclease protection assays both proteins protected an internal sequence and the
dsDNA ends equally well. Similarly, using electrophoretic mobility shift assays,
we found the affinity of both Rad52 and Rad59 proteins for DNA ends to be
comparable with their affinity for internal sequences. The protein-DNA complexes
were also directly visualized using atomic force microscopy. Both proteins formed
discrete complexes, which were primarily found (90-94%) at internal dsDNA sites.
We also measured the DNA end binding behavior of human Rad52 protein and found a
slight preference for dsDNA ends. Thus, these proteins have no strong preference
for dsDNA ends over internal sites, which is inconsistent with their function at
a step of dsDNA break repair that precedes DNA processing. Therefore, we conclude
that S. cerevisiae Rad52 and Rad59 proteins and their eukaryotic counterparts
function by binding to single-stranded DNA formed as intermediates of
recombination rather than by binding to the unprocessed DNA double-strand break.
PMID- 17040916
TI - Mammalian transcription in support of hybrid mRNA and protein synthesis in testis
and lung.
AB - Post-transcriptional mechanisms including differential splicing expand the
protein repertoire beyond that provided by the one gene-one protein model. Trans
splicing has been observed in mammalian systems but is low level (sometimes
referred to as noise), and a contribution to hybrid protein expression is
unclear. In the study of rat sperm tail proteins a cDNA, called 1038, was
isolated representing a hybrid mRNA derived in part from the ornithine
decarboxylase antizyme 3 (Oaz3) gene located on rat chromosome 2 fused to
sequences encoded by a novel gene on chromosome 4. Cytoplasmic Oaz3 mRNA is
completely testis specific. However, in several tissues Oaz3 is transcribed and
contributes to hybrid 1038 mRNA synthesis, without concurrent Oaz3 mRNA
synthesis. 1038 mRNA directs synthesis of a hybrid 14-kDa protein, part
chromosome 2- and part chromosome 4-derived as shown in vitro and in transfected
cells. Antisera that recognize a chromosome 4-encoded C-terminal peptide confirm
the hybrid character of endogenous 14-kDa protein and its presence in sperm tail
structures and 1038-positive tissue. Our data suggest that the testis-specific
OAZ3 gene may be an example of a mammalian gene that in several tissues is
transcribed to contribute to a hybrid mRNA and protein. This finding expands the
repertoire of known mechanisms available to cells to generate proteome diversity.
PMID- 17040917
TI - Molecular adaptation and allostery in plant pantothenate synthetases.
AB - Pantothenate synthetase catalyzes the ATP-dependent condensation of pantoate and
beta-alanine to yield pantothenate, the essential precursor to coenzyme A.
Bacterial and plant pantothenate synthetases are dimeric enzymes that share
significant sequence identity. Here we show that the two-step reaction mechanism
of pantothenate synthetase is conserved between the enzymes from Arabidopsis
thaliana and Escherichia coli. Strikingly, though, the Arabidopsis enzyme
exhibits large allosteric effects, whereas the Escherichia coli enzyme displays
essentially non-allosteric behavior. Our data suggest that specific subunit
contacts were selected and maintained in the plant lineage of the pantothenate
synthetase protein family and that the resulting allosteric interactions are
balanced for efficient catalysis at low pantoate levels. This is supported by
mutations in the putative subunit interface of Arabidopsis pantothenate
synthetase, which strongly attenuated or otherwise modified its allosteric
properties but did not affect the dimeric state of the enzyme. At the molecular
level, plant pantothenate synthetases exemplify functional adaptation through
allostery and without alterations to the active site architecture. We propose
that the allosteric behavior confers a selective advantage in the context of the
subcellular compartmentation of pantothenate biosynthesis in plants.
PMID- 17040918
TI - The Arabidopsis protein kinase PTI1-2 is activated by convergent phosphatidic
acid and oxidative stress signaling pathways downstream of PDK1 and OXI1.
AB - Arabidopsis PDK1 activity is regulated by binding to the lipid phosphatidic acid
(PA) resulting in activation of the oxidative stress-response protein kinase
OXI1/AGC2-1. Thus there is an inferred link between lipid signaling and oxidative
stress signaling modules. Among a panel of hormones and stresses tested, we found
that, in addition to PA, the fungal elicitor xylanase activated PDK1, suggesting
that PDK1 has a role in plant pathogen defense mechanisms. The downstream OXI1
was activated by additional stress factors, including PA, H(2)O(2), and partially
by xylanase. We have isolated an interacting partner of OXI1, a Ser/Thr kinase
(PTI1-2), which is downstream of OXI1. Its sequence closely resembles the tomato
Pti kinase, which has been implicated in the hypersensitive response, a localized
programmed cell death that occurs at the site of pathogen infection. PTI1-2 is
activated by the same stresses/elicitors as OXI1 and additionally flagellin. We
have used RNA interference to knock out the expression of PDK1 and OXI1 and to
study the effects on PTI1-2 activity. We show that specific lipid signaling
pathways converge on PTI1-2 via the PDK1-OXI1 axis, whereas H(2)O(2) and
flagellin signals to OXI1-PTI1-2 via a PDK1-independent pathway. PTI1-2
represents a new downstream component that integrates diverse lipid and reactive
oxygen stress signals and functions closely with OXI1.
PMID- 17040919
TI - Hydrophobic interface between two regulators of K+ conductance domains critical
for calcium-dependent activation of large conductance Ca2+-activated K+ channels.
AB - It has been suggested that the large conductance Ca(2)+-activated K(+) channel
contains one or more domains known as regulators of K(+) conductance (RCK) in its
cytosolic C terminus. Here, we show that the second RCK domain (RCK2) is
functionally important and that it forms a heterodimer with RCK1 via a
hydrophobic interface. Mutant channels lacking RCK2 are nonfunctional despite
their tetramerization and surface expression. The hydrophobic residues that are
expected to form an interface between RCK1 and RCK2, based on the crystal
structure of the bacterial MthK channel, are well conserved, and the interactions
of these residues were confirmed by mutant cycle analysis. The hydrophobic
interaction appears to be critical for the Ca(2+)-dependent gating of the large
conductance Ca(2+)-activated K(+) channel.
PMID- 17040920
TI - Inherent limitations in protein-protein docking procedures.
AB - MOTIVATION: The limited success rate of protein-protein docking procedures is
generally attributed to structure differences between the bound and unbound
states of the molecules. Herein we analyze a large dataset of protein-protein
docking results and identify additional parameters that affect the performance of
docking procedures. RESULTS: We find that the distinction between nearly correct
models (NCMs) and decoys depends on the size of the interface to be predicted
thus setting a limit to the prediction ability of docking procedures,
particularly those in which the geometric complementarity descriptor is dominant.
The geometric complementarity score in grid-based docking carries a large
statistical error which further reduces the distinction between NCMs and decoys.
We propose a method for correcting the statistical error and show that the
distinction is improved when the docking models are ranked by statistically
equivalent scores. AVAILABILITY: MolFit can be downloaded from our website
http://www.weizmann.ac.il/Chemical_Research_Support/molfit. SUPPLEMENTARY
INFORMATION: Supplementary data are available at Bioinformatics online.
PMID- 17040921
TI - Striosomes and mood dysfunction in Huntington's disease.
AB - Variable phenotype is common in neurological disorders with single-gene
inheritance patterns. In Huntington's disease, mood and cognitive symptoms are
variably co-expressed with motor symptoms. There is also variable degeneration of
neurons in the two major neurochemical compartments of the striatum, the
striosomes and the extrastriosomal matrix. To determine whether the phenotypic
variability in Huntington's disease is related to this compartmental
organization, we carried out a double-blind study in which we used GABA(A)
receptor immunohistochemistry to analyse the status of striosomes and matrix in
the brains of 35 Huntington's disease cases and 13 control cases, and collected
detailed data on the clinical symptomatology expressed by the patients from
family members and records. We report here a significant association between
pronounced mood dysfunction in Huntington's disease patients and differential
loss of the GABA(A) receptor marker in striosomes of the striatum. This
association held for both clinical onset and end-stage assessments of symptoms.
The cases with accentuated striosome abnormality further exhibited later onset
age, lower disease grade and lower CAG repeat length in the HD gene. We found no
independent association, however, between CAG repeat length or age of onset and
mood dysfunction. We suggest that variation in clinical symptomatology in
Huntington's disease is associated with variation in the relative abnormality of
GABA(A) receptor expression in the striosome and matrix compartments of the
striatum, and that striosome-related circuits may modulate mood functioning.
PMID- 17040922
TI - Bactericidal agents in the treatment of MRSA infections--the potential role of
daptomycin.
AB - Over the last decade, methicillin-resistant Staphylococcus aureus (MRSA) strains
have emerged as serious pathogens. These strains are often multiresistant to
several antibiotic classes and are a major cause of serious hospital- and now
community-acquired infections and associated morbidity and mortality. As a result
of increasing antimicrobial resistance, glycopeptides, such as vancomycin, are
widely used as first-line therapy for serious MRSA infections. However, the
emergence of glycopeptide tolerance and resistance has complicated treatment and
there remains a clinical need for new antibiotics with suitable pharmacokinetic
properties with activity against MRSA and other gram-positive pathogens.
Infections caused by MRSA and other bacteria usually respond as well to
bacteriostatic agents as to bactericidal ones. Nevertheless, there is evidence
that rapid bacterial killing has potential clinical advantages over
bacteriostatic therapy in certain infections. Daptomycin, the first of the cyclic
lipopeptides, shows rapid bactericidal activity against S. aureus, including
strains tolerant or resistant to other agents. This review outlines the methods
by which bactericidal and bacteriostatic properties are defined and tested,
discusses the potential importance of bactericidal therapy in MRSA and other
infections and examines the potential role of daptomycin in treatment.
PMID- 17040923
TI - Analysis of the mechanisms of fluoroquinolone resistance in urinary tract
pathogens.
AB - OBJECTIVES: To characterize the mechanisms of fluoroquinolone resistance in
urinary tract pathogens exhibiting a multiple antibiotic resistance phenotype as
well as a high-level resistance to fluoroquinolones. METHODS: Nineteen
Escherichia coli urinary tract infection pathogens exhibiting high-level
resistance to fluoroquinolones were characterized in this study. Alterations in
outer membrane proteins (OMPs) and lipopolysaccharide (LPS) were analysed by
PAGE. Changes to the quinolone resistance-determining regions (QRDRs) of GyrA and
ParC were determined by PCR and DNA sequencing. The presence of the qnrA gene was
determined by PCR amplification. Ciprofloxacin uptake was determined
spectrophotometrically using the quinolone accumulation assay. RESULTS: OMP
analysis showed decreased expression, the absence of certain proteins or the
presence of proteins with altered molecular weights when compared with wild-type
strains. Most isolates possessed a smooth LPS phenotype. Isolates had double
mutations in GyrA codons 83 and 87, in addition to a ParC alteration at Ser
80/Glu-84. Isolates accumulated varying levels of ciprofloxacin, and upon the
addition of carbonyl cyanide m-chlorophenylhydrazone, increased accumulation was
observed in all instances. E. coli isolates with a rough LPS phenotype appeared
to accumulate higher levels of ciprofloxacin compared with those with a smooth
LPS phenotype expressing OmpF normally, or even those not possessing OmpF. All E.
coli isolates tested demonstrated active efflux of ciprofloxacin. Plasmid
mediated quinolone resistance (presence of the qnrA gene) was observed in 36.8%
of isolates. CONCLUSIONS: A combination of target gene alterations, altered OM
permeability, presence of the qnrA gene and active efflux appear to act together
to produce a high-level, multiresistance phenotype.
PMID- 17040924
TI - Prevention of HIV and sexually transmitted diseases in high risk social networks
of young Roma (Gypsy) men in Bulgaria: randomised controlled trial.
AB - OBJECTIVE: To determine the effects of a behavioural intervention for prevention
of HIV and sexually transmitted diseases that identified, trained, and engaged
leaders of Roma (Gypsy) men's social networks to counsel their own network
members. DESIGN: A two arm randomised controlled trial. SETTING: A disadvantaged,
impoverished Roma settlement in Bulgaria. PARTICIPANTS: 286 Roma men from 52
social networks recruited in the community. INTERVENTION: At baseline all
participants were assessed for HIV risk behaviour, tested and treated for
sexually transmitted diseases, counselled in risk reduction, and randomised to
intervention or control groups. Network leaders learnt how to counsel their
social network members on risk prevention. Networks were followed up three and 12
months after the intervention to determine evidence of risk reduction. MAIN
OUTCOME MEASURE: Occurrence of unprotected intercourse during the three months
before each assessment. RESULTS: Reported prevalence of unprotected intercourse
in the intervention group fell more than in control group (from 81% and 80%,
respectively, at baseline to 65% and 75% at three months and 71% and 86% at 12
months). Changes were more pronounced among men with casual partners. Effects
remained strong at long term follow-up, consistent with changes in risk reduction
norms in the social network. Other measures of risk reduction corroborated the
intervention's effects. CONCLUSIONS: Endorsement and advice on HIV prevention
from the leader of a social network produces well maintained change in the
reported sexual practices in members of that network. This model has particular
relevance for health interventions in populations such as Roma who may be
distrustful of outsiders. TRIAL REGISTRATION: Clinical Trials NCT00310973.
PMID- 17040925
TI - Effect of baseline serum albumin concentration on outcome of resuscitation with
albumin or saline in patients in intensive care units: analysis of data from the
saline versus albumin fluid evaluation (SAFE) study.
AB - OBJECTIVE: To determine whether outcomes of resuscitation with albumin or saline
in the intensive care unit depend on patients' baseline serum albumin
concentration. DESIGN: Analysis of data from a double blind, randomised
controlled trial. SETTING: Intensive care units of 16 hospitals in Australia and
New Zealand. PARTICIPANTS: 6045 participants in the saline versus albumin fluid
evaluation (SAFE) study. INTERVENTIONS: Fluid resuscitation with 4% albumin or
saline in patients with a baseline serum albumin concentration of 25 g/l or less
or more than 25 g/l. MAIN OUTCOME MEASURES: Primary outcome was all cause
mortality at 28 days. Secondary outcomes were length of stay in the intensive
care unit, length of stay in hospital, duration of renal replacement therapy, and
duration of mechanical ventilation. MAIN RESULTS: The odds ratios for death for
albumin compared with saline for patients with a baseline serum albumin
concentration of 25 g/l or less and more than 25 g/l were 0.87 and 1.09,
respectively (ratio of odds ratios 0.80, 95% confidence interval 0.63 to 1.02);
P=0.08 for heterogeneity. No significant interaction was found between baseline
serum albumin concentration as a continuous variable and the effect of albumin
and saline on mortality. No consistent interaction was found between baseline
serum albumin concentration and treatment effects on length of stay in the
intensive care unit, length of hospital stay, duration of renal replacement
therapy, or duration of mechanical ventilation. CONCLUSION: The outcomes of
resuscitation with albumin and saline are similar irrespective of patients'
baseline serum albumin concentration. TRIAL REGISTRATION: ISRCTN76588266.
PMID- 17040926
TI - Self management of arthritis in primary care: randomised controlled trial.
AB - OBJECTIVE: To evaluate clinical effectiveness of a self management programme for
arthritis in patients in primary care with osteoarthritis. DESIGN: Randomised
controlled trial. SETTING: 74 general practices in the United Kingdom.
PARTICIPANTS: 812 patients aged 50 and over with osteoarthritis of hips or knees
(or both) and pain or disability (or both). INTERVENTION: Participants were
randomised to six sessions of self management of arthritis and an education
booklet (intervention group) or the education booklet alone (control group). MAIN
OUTCOME MEASURES: Primary outcome was quality of life, as assessed by the short
form health survey (SF-36). Several other physical and psychosocial secondary
outcomes were assessed. Data were collected at baseline, four months, and 12
months. RESULTS: Response rates were 80% and 76% at four and 12 months. The two
groups showed significant differences at 12 months on the anxiety subscore of the
hospital anxiety and depression scale (mean difference -0.62, 95% confidence
interval -1.08 to -0.16), arthritis self efficacy scale for pain (0.98, 0.07 to
1.89), and self efficacy for other aspects of management (1.58, 0.25 to 2.90).
Results were similar for intention to treat and per protocol analyses. No
significant difference was seen in number of visits to the general practitioner
at 12 months. CONCLUSIONS: The self management of arthritis programme reduced
anxiety and improved participants' perceived self efficacy to manage symptoms,
but it had no significant effect on pain, physical functioning, or contact with
primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79115352
[controlled-trials.com].
PMID- 17040927
TI - Diabetes mellitus and infective endocarditis: the insulin factor in patient
morbidity and mortality.
AB - AIMS: To analyse the characteristics of infective endocarditis (IE) in patients
with diabetes mellitus (DM), and to evaluate the prognostic significance of DM
according to insulin use. METHODS AND RESULTS: A total of 559 patients with
definite IE including 75 patients (13%) with DM (insulin use n = 22; oral
antidiabetic n = 53) were evaluated. Comparison of insulin-DM, oral-DM, and non
DM patients showed an older age (66 +/- 13, 66 +/- 10, 58 +/- 17, respectively; P
= 0.004) in DM patients, and more frequent IE on prosthetic valves (32, 11, and
15%, respectively; P = 0.068) in insulin-DM patients. Oral streptococci (0, 8,
and 18%, respectively; P = 0.016) were less frequently the causative organism
than staphylococci (64, 26, and 29%, respectively; P = 0.002) in insulin-DM
patients. Vegetations, dehiscence, abscess, and regurgitation rates did not
differ among the three groups, nor did cardiac surgery rates (32, 47, and 48%,
respectively; P = 0.334), but in-hospital mortality was higher in insulin-DM
patients (50, 19, and 15%; P < 0.001). In multivariable analysis, independently
of other determinants of death (age, IE location, Staphylococcus aureus, history
of heart failure, immunosuppression, creatinine serum), insulin-DM was a
predictor of death (OR, 4.69; 95% CI, 1.77-12.44), whereas oral-DM was not.
CONCLUSION: IE prognosis in insulin-DM patients is poor due to the coexistence of
host and pathogen factors. Insulin-DM patients with IE may require specific
management.
PMID- 17040928
TI - The impact of anthropomorphic indices on clinical outcomes in patients with acute
ST-elevation myocardial infarction.
AB - AIMS: Multiple studies have focused on the relationship of body anthropometric
measures with clinical events in ST-elevation myocardial infarction (STEMI)
patients, highlighting the 'obesity paradox'. However, the relative prognostic
importance of these measures over other baseline variables is less known. METHOD
AND RESULTS: We performed a retrospective analysis of 94,108 STEMI patients from
seven clinical trials evaluating various reperfusion strategies to study the
relationship and prognostic importance of height, weight, body mass index (BMI),
and body surface area (BSA) with 30-day death and in-hospital cardiogenic shock,
major bleeding, and stroke. Main outcome measures of interest included 30-day
death and in-hospital cardiogenic shock, major bleeding, and stroke. Weight, BMI,
and BSA were inversely and independently related to all clinical events. Despite
being statistically significant (P<0.0001), the prognostic information
contributed by weight beyond that conferred by baseline clinical factors was
minimal (<1% of total prognostic information) making it of limited clinical
relevance for predicting 30-day death and cardiogenic shock. In contrast, weight
accounted for 8.4% and 4.3% of the prognostic information in the logistic
regression models for major bleeding and for stroke. BMI or BSA added little
incremental value over simple measure of weight. CONCLUSION: Although
statistically significantly related to most outcomes in patients with STEMI
including death and shock, body weight provided clinically relevant prognostic
information only for the risk of major bleeding and of stroke. Furthermore, BMI
or BSA contributed little incremental prognostic information beyond that provided
by weight alone. Thus, the existing large body of information concerning the
strong prognostic importance of anthropometric measures with outcomes after STEMI
should be interpreted in the context of other more important risk factors.
PMID- 17040929
TI - Coronary plaque composition of culprit/target lesions according to the clinical
presentation: a virtual histology intravascular ultrasound analysis.
AB - AIMS: To evaluate the plaque composition obtained by virtual histology (VH) IVUS
according to the clinical presentation and to compare those data to previously
published histopathology data. METHODS AND RESULTS: VH was performed on 95 de
novo significant lesions (>75% stenosis) in 85 patients [28 acute coronary
syndrome (ACS) patients, 30 lesions; 57 stable angina pectoris (SAP) patients, 65
lesions]. There were a higher prevalence of positive remodelling (47 vs. 22%,
P=0.013), thrombus (20 vs. 1.5%, P=0.0037), and echo-lucent area (23.3 vs. 7.7%,
P=0.047) in ACS patients. At the minimal lumen site, fibrous plaque area was
significantly larger in ACS lesions than in SAP lesions (66.0+/-10.7 vs. 61.4+/
8.9%, P=0.034), whereas necrotic core and dense calcium plaque area were smaller
in ACS lesions (Necrotic core: 6.8+/-6.0 vs. 11.0+/-8.3%, P=0.02; Dense calcium:
2.6+/-3.0 vs. 4.9+/-5.8%, P=0.03). No differences in rate of thin cap
fibroatheroma, thick fibrotheroma, or for the presence of multiple necrotic core
layers were observed between both groups. CONCLUSION: Plaque composition obtained
by VH-IVUS shows less necrotic core and more fibrous tissue in ACS compared to
SAP lesions, which is in contradiction with previously published histopathologic
data.
PMID- 17040930
TI - A modified back-etch method for preparation of plan-view high-resolution
transmission electron microscopy samples.
AB - A modified back-etch method is described that has been successfully used to
prepare samples of thin films and nanoparticles on Si wafer substrates for
examination by high-resolution transmission electron microscopy (HRTEM). This
process includes ultrasonic cutting, abrasive pre-thinning and a two-stage
etching procedure. Unlike previous reports of back-etching methods, tetramethyl
ammonium hydroxide, which has a very high-etching selectivity of Si to SiO(2), is
used for the final etching to allow removal of the Si without degradation of the
SiO(2) membrane. An innovative wrapping method is also described. This novel
approach reduces the preparation time for HRTEM samples to <1 h per sample for
groups of 10 or more samples. As an example, the preparation of FePt nanoparticle
samples for HRTEM imaging is described.
PMID- 17040931
TI - The association of sequence variants in DNA repair and cell cycle genes with
cancers of the upper aerodigestive tract.
AB - Cancers of the upper aerodigestive tract (UADT), comprising the oral cavity,
pharynx, larynx and oesophagus, account for 5.2% of all cancers cases worldwide.
The major risk factors, tobacco and alcohol can directly or indirectly generate
DNA damage, which if unrepaired can give rise to mutations, unregulated cell
growth and apoptosis induction. To clarify the role of DNA repair and cell cycle
control proteins in UADT cancer susceptibility, we studied the risk in relation
to 28 SNPs in 18 DNA repair enzymes and 9 SNPs in 7 cell cycle control genes. A
case-control study was conducted from 2000 to 2002 in six centers from Romania,
Poland, Russia, Slovakia and the Czech Republic. Patients diagnosed with squamous
cell carcinoma of the UADT (n=811) and controls with a recent diagnosis of
diseases unrelated to tobacco and alcohol (n=1083) were recruited. For UADT
cancer risk, associations were observed for the homozygous carriers of the
variant alleles of MGMT L84F [odds ratio (OR) 2.35, 95% confidence interval (CI)
1.32-4.20], MGMT 171C > T (OR 2.24, 95% CI 1.20-4.17) and OGG1 S326C (OR 2.07,
95% CI 1.15-3.73) whilst three variants were associated with a protective effect
(XPA 23G > A, P for trend 0.022, APEX Q51H, P for trend 0.036, CHEK2 intron 9
200T > C, P for trend 0.009). Several other sequence variants showed associations
with specific cancers without an overall association with UADT cancer. While some
of these associations are consistent with previous studies, we cannot rule out
the possibility of false-positive associations. The positive findings should be
explored in another large-scale study on UADT cancers.
PMID- 17040932
TI - Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive
pulmonary disease in a nationally representative population sample.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth most
common cause of death worldwide. It is caused primarily by cigarette smoking.
Given its importance, it is remarkable that reliable national prevalence data are
lacking for most countries. This study provides estimates of the national
prevalence of COPD in England, the extent of under-detection of the disorder, and
patterns of cigarette smoking, dependence, and motivation to stop smoking in
those with the disease. METHODS: Data from 8215 adults over the age of 35 who
participated in the Health Survey for England were analysed. Information was
obtained on self-reported and cotinine validated smoking status, cigarette
dependence, motivation to stop smoking, COPD defined by spirometry using joint
American Thoracic Society and European Respiratory Society criteria, and self
reports of diagnosis with respiratory disorders. RESULTS: Spirometry-defined COPD
was present in 13.3% (95% CI 12.6 to 14.0) of participants, over 80% of whom
reported no respiratory diagnosis. Even among people with severe or very severe
COPD by spirometric assessment, only 46.8% (95% CI 39.1 to 54.6) reported any
diagnosed respiratory disease. A total of 34.9% (95% CI 32.1 to 37.8) of people
with spirometry-defined COPD were smokers compared with 22.4% (95% CI 21.4 to
23.4) of those without, and smoking prevalence increased with disease severity.
Smokers with spirometry-defined COPD were more cigarette dependent but had no
greater desire to quit than other smokers. CONCLUSION: COPD is common among
adults in England and is predominantly undiagnosed. In smokers it is associated
with higher degrees of cigarette dependence but not with a greater motivation to
stop smoking.
PMID- 17040933
TI - Outcome of occupational asthma after cessation of exposure: a systematic review.
AB - BACKGROUND: Patients with occupational asthma, and their medical advisers, need
valid information about the prognosis of their disease. METHODS: A systematic
review of the published literature on the symptomatic and functional outcomes of
occupational asthma was carried out after avoidance of exposure to the causative
agent. Through a full search of electronic and bibliographic sources, original
studies documenting complete recovery from asthma (n = 39,1681 patients) or
improvement in non-specific bronchial hyper-responsiveness (NSBHR; n = 28,695
patients) were identified. The median duration of follow-up was 31 (range 6-240)
months for studies of symptomatic recovery and 37 (6-240) months for studies of
NSBHR. Most studies were of patients recruited from special clinics. RESULTS:
Reported rates of symptomatic recovery varied from 0% to 100%, with a pooled
estimate of 32% (95% CI 26% to 38%). These rates were lower with increasing age
(p = 0.019) and among clinic based populations (p = 0.053). Patients with the
shortest durations of exposure (< or =76 months) had the highest rate of recovery
(36%; 95% CI 25% to 50%), but the effect was not linear. The pooled prevalence of
persistent NSBHR at follow-up was 73% (95% CI 66% to 79%). This figure was higher
among patients whose disease was due to high-molecular-weight agents (p = 0.006)
and, less clearly, those from clinic-based populations (p = 0.561). In between
study comparisons, no clear patterns of improvement relating to total duration of
exposure or follow-up were found. From within-study comparisons there was some
evidence that a shorter duration of symptoms was associated with a higher rate of
symptomatic recovery. CONCLUSION: The available data on the prognosis of
occupational asthma are insufficiently consistent to allow confident advice to be
given to patients with the disease. Clinicians and epidemiologists with an
interest in this disease should consider a collaborative and carefully
standardised study of the prognosis of occupational asthma.
PMID- 17040934
TI - Air travel in women with lymphangioleiomyomatosis.
AB - BACKGROUND AND OBJECTIVE: The safety of air travel in patients with pneumothorax
prone pulmonary diseases, such as lymphangioleiomyomatosis (LAM), has not been
studied to any great extent. A questionnaire-based evaluation of air travel in
patients with LAM was conducted to determine experiences aboard commercial
aircraft. METHODS: A survey was sent to women listed in the US LAM Foundation
registry (n = 389) and the UK LAM Action registry (n = 59) to assess air travel,
including problems occurring during flight. Women reporting a pneumothorax in
flight were followed up to ascertain further details about the incident. RESULTS:
327 (73%) women completed the survey. 308 women answered the travel section, of
whom 276 (90%) had "ever" travelled by aeroplane for a total of 454 flights. 95
(35%) women had been advised by their doctor to avoid air travel. Adverse events
reported included shortness of breath (14%), pneumothorax (2%, 8/10 confirmed by
chest radiograph), nausea or dizziness (8%), chest pain (12%), unusual fatigue
(11%), oxygen desaturation (8%), headache (9%), blue hands (2%), haemoptysis
(0.4%) and anxiety (22%). 5 of 10 patients with pneumothorax had symptoms that
began before the flight: 2 occurred during cruising altitude, 2 soon after
landing and 1 not known. The main symptoms were severe chest pain and shortness
of breath. DISCUSSION AND CONCLUSION: Adverse effects occurred during air travel
in patients with LAM, particularly dyspnoea and chest pain. Hypoxaemia and
pneumothorax were reported. The decision to travel should be individualised;
patients with unexplained shortness of breath or chest pain before scheduled
flights should not board. Patients with borderline oxygen saturations on the
ground should be evaluated for supplemental oxygen therapy during flight.
Although many women had been advised not to travel by air, most travelled without
the occurrence of serious adverse effects.
PMID- 17040935
TI - Does living near heavy industry cause lung cancer in women? A case-control study
using life grid interviews.
AB - BACKGROUND: The incidence of lung cancer among women is high in the highly
industrialised area of Teesside in north-east England. Previous research has
implicated industrial pollution as a possible cause. A study was undertaken to
investigate whether prolonged residence close to heavy industry is associated
with lung cancer among women in Teesside. METHODS: Two hundred and four women
aged <80 years with incident primary lung cancer and 339 age matched community
controls were recruited to a population based case-control study. Life course
residential, occupational, and active and passive smoking histories were obtained
using an interviewer administered questionnaire. RESULTS: The age adjusted odds
ratio (OR) for lung cancer among people living >25 years v 0 years near (within 0
5 km) heavy industry in Teesside was 2.13 (95% CI 1.34 to 3.38). After adjustment
for confounding factors the OR was 1.83 (95% CI 0.82 to 4.08) for >25 years or
1.10 (95% CI 0.96 to 1.26) for an additional 10 years living near industry. ORs
were similar after residence near heavy industry outside Teesside was also
included, and when latency was allowed for by disregarding residential exposures
within the last 20 years. Adjustment for active smoking had the greatest effect
on the OR. CONCLUSIONS: This population based study using life grid interviews
for life course exposure assessment has addressed many deficiencies in the design
of previous studies. The findings support those in most of the international
literature of a modestly raised risk of lung cancer with prolonged residence
close to heavy industry, although the confidence intervals were wide. The effect
of air pollution on the incidence of lung cancer merits continued study.
PMID- 17040936
TI - Asthma is associated with preterm birth but not with small for gestational age
status among a population-based cohort of Medicaid-enrolled children <10 years of
age.
AB - BACKGROUND: Few population-based studies have evaluated the association between
birth weight or gestation and subsequent clinically significant asthma. METHODS:
Birth records of 37 349 Alaska residents <10 years of age who were enrolled in
Medicaid for at least 365 days during 1999-2002 were linked to a Medicaid billing
file. The occurrence of asthma and lower respiratory infections during the study
period was categorised on the basis of standard International Classification of
Diseases 9th Revision codes. The association between gestational age or small for
gestational age status and asthma outcomes was adjusted for recent history of
lower respiratory infection, years of Medicaid enrolment, age at enrolment and a
variety of birth-related factors. RESULTS: Among children <5 years of age, the
adjusted odds ratio (OR) for developing asthma decreased by 5.5% (95% confidence
interval (CI) -0.2 to 10.9) and 7.9% (95% CI 5.2 to 10.4) per additional week of
gestational age for children without and with any lower respiratory tract
infection, respectively. For children > or =5 years of age, the adjusted OR for
developing asthma decreased by 3.4% (95% CI -2.8 to 9.8) and 3.7% (95% CI -2.0 to
9.2) per additional week of gestation for those without and with lower
respiratory tract infection, respectively. Among all children with asthma, the
adjusted OR for hospitalisation due to asthma decreased by 6.9% (95% CI 2.1 to
11.5) for each additional week of gestational age. Small for gestational age
status was not significantly associated with asthma outcomes. CONCLUSIONS:
Preterm birth but not small for gestational age status predicted subsequent
asthma outcomes. Adverse effects of preterm birth on asthma outcomes persist
beyond age 5 years.
PMID- 17040937
TI - Maternal effects on docility in Limousin cattle.
AB - The objective of this study was to quantify the role of maternal effects on
docility in Limousin cattle. Docility scores were obtained at weaning while
animals were restrained in a squeeze chute. Scores 1 through 6 represented a
docile to aggressive temperament, respectively, and were provided by the North
American Limousin Foundation. Observations with unknown age of dam, contemporary
groups containing less than 10 observations, contemporary groups with no
variation, and single-sire contemporary groups were removed, leaving 21,932
observations. A 2-generation pedigree file compiled from animals with
observations contained 49,459 animals. Fixed effects were weaning contemporary
group and age of dam (2, > or =3 yr). Six animal models encompassed combinations
of random factors: direct genetic, maternal genetic, and maternal permanent
environmental effects. The model D was the most basic, containing direct genetic
and residual effects, and it resembled the method currently used by the North
American Limousin Foundation for genetic evaluation of docility. Maternal genetic
or permanent environmental effects were separately added to the model D, denoted
as models DM and DC, respectively. Model DMC contained all random factors. Models
DM-Zero and DMC-Zero were equivalent to models DM and DMC, respectively, but with
zero direct-maternal genetic covariance. Direct heritability estimates were
moderate for all models (0.29 +/- 0.02 to 0.38 +/- 0.03). Maternal heritability
estimates were low, ranging from 0.01 +/- 0.01 (DM-Zero) to 0.05 +/- 0.02 (DM).
Negative direct-maternal genetic correlations of -0.41 +/- 0.09 and -0.55 +/-
0.09 were estimated for models DM and DMC, respectively. The proportion of
phenotypic variance accounted for by maternal permanent environmental effects was
0.03 +/- 0.01, 0.04 +/- 0.01, and 0.02 +/- 0.01 for models DC, DMC, and DMC-Zero,
respectively. Likelihood ratio tests indicated that model DMC best fit the data.
Although maternal genetic and maternal permanent environmental effects were
significant, they accounted for only 8% (model DMC) of the phenotypic variance,
and a Spearman rank correlation of 0.99 between models D and DMC showed sires did
not rank differently with or without inclusion of these effects. Given these
results, inclusion of maternal effects to the genetic evaluation of docility in
Limousin cattle does not seem warranted.
PMID- 17040938
TI - Analysis of litter size and days to lambing in the Ripollesa ewe. I. Comparison
of models with linear and threshold approaches.
AB - The analysis focused on model fitting of 2 ewe reproductive traits, litter size,
and days to lambing (interval between the introduction of the ram into the flock
and the subsequent parturition of the ewes). The experimental data set of the
Universitat Autonoma of Barcelona flock was used, including 1,598 records of
litter size and 1,699 records of days to lambing from 376 Ripollesa ewes between
1986 and 2005. Univariate and bivariate models were considered as beginning
points with linear or threshold approximation for litter size. Model fitting was
evaluated in terms of goodness-of-fit and predictive ability, using the mean
square error and the correlation between phenotypic and predicted records
(rho(y,y)) as reference parameters. The bivariate model was preferable for both
variables, minimizing mean square error and maximizing rho(y,y). A threshold
approximation for litter size was preferable over a linear approximation. Models
were also compared with a simulation study, comparing the correlation coefficient
between simulated and predicted breeding values (rho(a,a)). The bivariate
threshold model was favored, with a rho(y,y) of 0.677 and 0.834 for litter size
and days to lambing, respectively. Correlation coefficients between simulated and
predicted breeding values in the bivariate linear model were reduced slightly to
0.651 and 0.831, respectively, and they were lowest with linear univariate models
(0.642 and 0.802). Although the bivariate models for ewe litter size and days to
lambing were more accurate than the univariate models, the threshold approaches
showed a greater advantage under the bivariate model. For the purpose of genetic
evaluation of litter size in sheep, use of the threshold-linear model seems
justified. In the Ripollesa breed, the evaluation of litter size can benefit from
recording birth weight.
PMID- 17040939
TI - Effect of manganese supplementation and source on carcass traits, meat quality,
and lipid oxidation in broilers.
AB - An experiment was conducted using a total of 336 one-day-old, Arbor Acres
commercial male broilers to investigate the effect of dietary Mn supplementation
on carcass traits, meat quality, lipid oxidation, relative enzyme activities in
abdominal fat and meat, and Mn-containing superoxide dismutase (MnSOD) mRNA level
in meat. Broilers were randomly allotted by BW to 1 of 8 replicate cages (6
chicks per cage) for each of 7 treatments in a completely randomized design
involving a 2 x 3 factorial + 1 arrangement of treatments. Dietary treatments
included the corn-soybean meal-based diet (control) and the basal diet
supplemented with 100 or 200 mg of Mn/kg as MnSO(4) x H(2)O, Mn AA A with a
chelation strength of 26.3 formation quotient (8.34% Mn), or Mn AA B with a
chelation strength of 45.3 formation quotient (6.48% Mn). Birds fed supplemental
Mn had lower (P < 0.10) percentages of abdominal fat, lipoprotein lipase (LPL),
and malate dehydrogenase activities and greater (P < 0.07) hormone-sensitive
lipase activities in abdominal fat than birds fed a control diet. Birds fed
supplemental Mn from Mn AA A or Mn AA B had lower (P < 0.05) LPL activities in
abdominal fat than those fed supplemental MnSO(4) x H(2)O. Birds fed supplemental
Mn had lower (P < 0.03) malondialdehyde content in leg muscle and greater (P <
0.02) MnSOD activities and MnSOD mRNA level in breast or leg muscle than those
fed the control diet. Birds fed supplemental Mn from Mn AA A had a greater (P <
0.02) MnSOD mRNA level in leg muscle than those fed supplemental MnSO(4) x H(2)O.
Results from this study indicated that organic Mn was more available than
inorganic Mn for decreasing LPL activity in abdominal fat of broilers, and
dietary Mn might reduce abdominal adipose deposition by decreasing LPL and malate
dehydrogenase activities or increasing hormone-sensitive lipase activity in
abdominal adipose tissue. The results also indicated that dietary Mn upregulated
muscle MnSOD gene expression pretranslationally in association with increased
MnSOD activity, which might explain the decrease of malondialdehyde content in
leg muscle.
PMID- 17040940
TI - Could the pale, soft, and exudative condition be explained by distinctive
histological characteristics?
AB - Pork quality depends on various genetic and environmental factors. Despite the
improvement of slaughter conditions, the PSE type is still one of the main
concerns in this field. This study was conducted on nonstressed animals to
evaluate the tissue characteristics of some muscles usually involved during
stress compared with a reference muscle, the M. triceps brachii, which is
actually not subject to stress-caused damages. Samples of M. triceps brachii, M.
longissimus dorsi, M. biceps femoris, and M. semimembranosus were taken from pigs
exhibiting 1 of the 3 HAL genotypes (NN, Nn, or nn) and 2 of the 3 RN genotypes
(rn+rn+ or rn+RN-). Histoenzymology and immunohistochemistry were used to compare
the fiber typing and capillary network in these muscles within these different
stress susceptibility genotypes. In comparison with the reference muscle, M.
triceps brachii, the combination of a high value of the number of type IIb fibers
and a low vascular network showed a primary effect on muscles usually involved
during stress. This led to the definition of a PSE index. A dramatic increase (P
< 0.001) in this PSE index was systematically found in muscles usually involved
in the PSE-type condition. These results show that distinctive histological
characteristics were associated with the vulnerability of some muscles
independently of the genotypes. Moreover, this study highlights the distinctive
histological features of each genotype and is likely to suggest some interactions
between them.
PMID- 17040941
TI - Simulation of cow-calf production with and without realistic levels of
variability.
AB - The Colorado beef cattle production model, a whole-herd, individual-animal, life
cycle simulation model, was used to determine if level of simulated variability
affects simulation results. Beyond variability created by deterministic equations
describing known biological relationships and direct input, the Colorado beef
cattle production model can produce additional variation in a number of traits
through its capacity to generate multinormal deviates for each animal. Runs
simulating cow-calf production under ample and sparse levels of nutrition were
performed with less than realistic and realistic levels of variability for mature
weight, milk production, gestation length, maintenance requirements, appetite,
and combinations thereof. Under poor nutrition, simulation with less than
realistic variability altered means for pregnancy rate, postpartum interval, milk
production, weaning weight, and mature weight by up to 14%, 8.6 d, 0.8 kg/d, 9.6
kg, and 19.1 kg, respectively, in addition to changing the output for numerous
other variables. The level of simulated variability affected the means of output
variables through 2 mechanisms: (1) change in potentials due to differential
culling, which can only take place if potentials are allowed to vary; and (2)
further interaction with the model's nonlinear, deterministic equations. Our
findings indicate that by not simulating realistic levels of variability, models
with nonlinear functions may yield misleading results.
PMID- 17040942
TI - Mutations in BMPR-IB and BMP-15 genes are associated with litter size in Small
Tailed Han sheep (Ovis aries).
AB - The Small Tailed Han is a prolific local sheep breed in China. The bone
morphogenetic protein receptor IB (BMPR-IB) gene, which affects the fecundity of
Booroola Merino sheep, and the bone morphogenetic protein 15 (BMP-15) gene, which
affects the fecundity of Inverdale, Hanna, Belclare, Cambridge, and Lacaune
sheep, were studied as candidate genes associated with the prolificacy of Small
Tailed Han sheep. Single nucleotide polymorphisms of BMPR-IB and BMP-15 genes
were detected in Small Tailed Han ewes (n = 188) by PCR-RFLP. The combined effect
of the 2 genes on the prolificacy of Small Tailed Han sheep was studied. The
results indicated that the same FecB mutation (Q249R) occurred in the BMPR-IB
gene in Small Tailed Han ewes as found in Booroola Merino ewes. The Small Tailed
Han ewes with genotypes FecB(B)/FecB(B) and FecB(B)/FecB(+) had 1.40 (P < 0.01)
and 1.11 (P < 0.01) more lambs, respectively, than those with genotype
FecB(+)/FecB(+). The same FecX(G) mutation (Q239Ter) of the BMP-15 gene was found
in Small Tailed Han ewes as in Belclare and Cambridge ewes. The Small Tailed Han
ewes with the heterozygous mutant FecX(G)/FecX(+) had 0.55 (P < 0.01) more lambs
than those with the wild-type FecX(+)/FecX(+). The Small Tailed Han ewes carrying
mutations in both BMPR-IB and BMP-15 genes had greater litter size than those
with either mutation alone. In view of our results, marker-assisted selection
using both BMPR-IB and BMP-15 genes is warranted to increase litter size in sheep
and will be of considerable economic value to sheep producers.
PMID- 17040943
TI - Lipid microencapsulation allows slow release of organic acids and natural
identical flavors along the swine intestine.
AB - The purpose of the present work was to investigate the in vivo concentrations of
sorbic acid and vanillin as markers of the fate of organic acids (OA) and natural
identical flavors (NIF) from a microencapsulated mixture and from the same
mixture non-microencapsulated, and the possible consequences on the intestinal
microbial fermentation. Fifteen weaned pigs were selected from 3 dietary groups
and were slaughtered at 29.5 +/- 0.27 kg of BW. Diets were (1) control; (2)
control supplemented with a blend of OA and NIF microencapsulated with
hydrogenated vegetable lipids (protected blend, PB); and (3) control supplemented
with the same blend of OA and NIF mixed with the same protective matrix in
powdered form but without the active ingredient coating (non-protected blend,
NPB). Stomach, cranial jejunum, caudal jejunum, ileum, cecum, and colon were
sampled to determine the concentrations of sorbic acid and vanillin contained in
the blend and used as tracers. Sorbic acid and vanillin were not detectable in
pigs fed the control, and their concentrations were not different in the stomach
of PB and NPB treatments. Pigs fed PB showed a gradual decrease of the tracer
concentrations along the intestinal tract, whereas pigs fed NPB showed a decline
of tracer concentration in the cranial jejunum and onwards, compared with the
stomach concentrations. Sorbic acid and vanillin concentrations along the
intestinal tract were greater (P = 0.02) in pigs fed PB compared with pigs fed
NPB. Pigs fed PB had lower (P = 0.03) coliforms in the caudal jejunum and the
cecum than pigs fed the control or NPB. Pigs fed the control or PB had a greater
(P = 0.03) lactic acid bacteria plate count in the cecum than pigs fed NPB, which
showed a reduction (P = 0.02) of lactic acid concentrations and greater (P =
0.02) pH values in the caudal jejunum. The protective lipid matrix used for
microencapsulation of the OA and NIF blend allowed slow-release of both active
ingredients and prevented the immediate disappearance of such compounds upon
exiting the stomach.
PMID- 17040944
TI - Inbreeding trends and pedigree analysis of Irish dairy and beef cattle
populations.
AB - The objective of this study was to determine the inbreeding levels and to analyze
the pedigree of Irish purebred populations of Charolais, Limousin, Hereford,
Angus, and Simmental beef cattle, as well as the Holstein-Friesian dairy breed.
Pedigree analyses included quantifying the depth of known pedigree, average
generation intervals, effective population size, the effective number of
founders, ancestors, and founder genomes, as well as identifying the most
influential animals within the current population of each breed. The annual rate
of increase in inbreeding over the past decade was 0.13% (P < 0.001) in the
Hereford, 0.06% (P < 0.001) in the Simmental, and 0.10% (P < 0.001) in the
Holstein-Friesian breeds. Inbreeding in the other breeds remained relatively
constant over the past decade. Herefords had the greatest mean inbreeding in
2004, at 2.19%, whereas Charolais had the lowest, at 0.54%. Over half of each
purebred population in 2004 was inbred to some degree; the population with the
greatest proportion of animals inbred was the Hereford breed (85%). All 6 breeds
displayed a generation interval of approximately 6 yr in recent years. In the
pure-bred females born in 2004, the 3 most influential animals contributed
between 11% (Limousin) and 24% (Hereford) of the genes. Effective population size
was estimated for the Hereford, Simmental, and Holstein-Friesian only, and was
64, 127, and 75, respectively. The effective number of founders varied from 55
(Simmental) to 357 (Charolais), whereas the effective number of ancestors varied
from 35 (Simmental and Hereford) to 82 (Limousin). Thus, despite the majority of
animals being inbred, the inbreeding level across breeds is low but rising at a
slow rate in the Hereford, Simmental, and Holstein-Friesian.
PMID- 17040945
TI - Variation in plasma growth hormone during first parity in lactating cows.
AB - This study analyzed genetic and phenotypic variation in plasma GH during
lactation in first parity dairy cows. The heritability and repeatability were
examined using an algorithm for separation of basal and peak concentrations and
different power transformations. Blood samples were obtained 17 times during
first parity in 85 Holstein, 67 Red Dane, and 62 Jersey cows and assayed for GH.
Each breed comprised 2 genetic groups; thus, a total of 6 genetic groups were
defined. Across genetic groups, cows were assigned to 1 of 2 total mixed rations
with a low or a normal energy concentration. The separation algorithm identified
only 4.0% of the plasma GH concentrations as peaks. After excluding peak
concentrations, the repeatability of GH during lactation was improved. A log
transformation was found appropriate for GH. The log-transformed GH
concentrations for lactating dairy cows had a heritability ranging between 0.14
in early lactation to 0.08 in mid and late lactation. The repeatability was 0.24
in early lactation and increased to between 0.58 and 0.61 in mid and late
lactation. We conclude that for GH concentrations in lactating cows that are
sampled infrequently, the exclusion of peak values to obtain a basal GH
concentration was not effective in clarifying phenotypic or genetic effects.
PMID- 17040946
TI - Development of computational models for the purpose of conducting individual
livestock and premises traceback investigations utilizing National Animal
Identification System-compliant data.
AB - Many of the efforts surrounding the development of the National Animal
Identification System have encompassed the identification of livestock production
and handling premises as well as individuals or herds of animals, whereas little
effort has been directed toward the ultimate goal of animal traceback within 48
h. A mock data set representative of the Colorado cattle population was created
for modeling of cattle traceability. Using this data set, algorithms were
developed to complete rapid and accurate traceback and traceforward of animals or
premises or both. On July 19, 2005, the Colorado Department of Public Health and
Environment, in conjunction with the Colorado Department of Agriculture,
conducted a test exercise pertaining to homeland security. The exercise team
randomly identified animal number 926,583 (of the 2 million total animals) as a
potentially infected animal of interest and requested a traceback of this animal.
Traceback was accomplished in 215 s, and 540 primary coresident animals were
identified. However, due to animal movements, the number of coresidents (animals
exposed, directly or indirectly, to the animal of interest) expanded with
coresidency level (level 1 = direct contact; level 2 = direct contact with an
animal that had direct contact with the animal of interest; level 3 = direct
contact with an animal that had contact with an animal that had direct contact
with the animal of interest, etc.) to more than 1.2 million coresidents at level
4, and more than 90% of all animals identified as a coresident at some level. In
addition to the coresidency results, the premises containing the coresidents were
identified and sorted by the number of coresidents. Because of animal movement,
all 19,391 premises included in the data set had coresidents at some level. This
exercise demonstrated the capability of the developed algorithms to complete
rapid traceback and the complexity of the resulting animal traceback output.
PMID- 17040947
TI - Associations of polymorphisms of the ovine prion protein gene with growth,
carcass, and computerized tomography traits in Scottish Blackface lambs.
AB - The objective of this study was to investigate and estimate the associations of
the ovine prion protein (PrP) genotypes with a wide range of performance traits
in Scottish Blackface lambs. Performance records of up to 7,138 sheep of known
PrP genotypes born from 1999 to 2004 in 2 experimental farms were utilized.
Performance traits studied were BW at birth, marking (when the sheep were
identified with permanent ear tags at an average age of 52 d), and weaning
(average age of 107 d); slaughter traits (BW at slaughter, slaughter age, carcass
weight, and carcass conformation); ultrasonic muscle and fat depths; and
computerized tomography-predicted carcass composition and carcass yield at
weaning. Different linear mixed models, including random, direct animal effect,
and up to 3 maternal effects (genetic, permanent, and temporary environmental)
were used for the different traits. The PrP genotype was included in the model as
a fixed effect, along with other fixed factors with significant effects (P <
0.05). Five separate analyses were carried out for each trait, differing in the
method of PrP genotypic classification. The first analysis was based on
classifying the sheep into categories according to all 9 available PrP genotypes.
In the other 4 analyses, sheep were categorized according to the number of each
PrP allele carried. Results showed that there were no significant differences
between PrP genotypes for any of the performance traits studied when all 9
genotypes were compared (first analysis). Similarly, performance of the lambs did
not significantly differ between genotypes with different numbers of ARR copies.
However, there were significant variations in a few traits with respect to the
number of ARQ, AHQ, and VRQ alleles carried. Heterozygous lambs for the AHQ or
the ARQ allele were significantly heavier at some ages than lambs of the other
genotypes. Lambs carrying the VRQ allele required approximately 10 d longer
finishing time (P = 0.01) and yielded carcasses approximately 0.5 kg heavier (P =
0.03) compared with noncarriers. The few significant associations found do not
have a negative influence on performance when selecting against the most
susceptible PrP allele (VRQ) or in favor of the most resistant one (ARR).
Overall, there were no major associations of PrP genotypes with most lamb
performance traits in Scottish Blackface sheep.
PMID- 17040948
TI - Effects of crude red kidney bean lectin (phytohemagglutinin) exposure on
performance, health, feeding behavior, and gut maturation of pigs at weaning.
AB - The aim of this study was to obtain information that could help to ease the
weaning transition in commercial pig production. Before weaning,
phytohemagglutinin (PHA) in the form of a crude preparation of red kidney bean
lectin was fed by gavage to 24 crossbred [(Swedish Landrace x Yorkshire) x
Hampshire] piglets, whereas 24 control piglets were fed alpha-lactalbumin by
gavage, to study the effect on growth, occurrence of postweaning diarrhea,
feeding behavior, and some anatomical and physiological traits of the
gastrointestinal tract. Within the litter, piglets were randomly assigned to PHA
treatment or control and remained in the same pen from the beginning (PHA
exposure at 7 d before weaning) until the end of the experiment (14 d post
weaning). Weaning took place at the age of 31 to 34 d. Pigs treated with PHA grew
faster (P = 0.013) during the first week postweaning and tended to have lower
total diarrhea scores (P = 0.10) than did control pigs. On d 5 after weaning,
piglets treated with PHA spent more time eating (P = 0.028) than control pigs. No
immunostimulating effect of PHA, measured by plasma immunoglobulin G, could be
detected. An increase in the intestinal barrier properties before weaning, as a
response to PHA treatment, was demonstrated in intestinal absorption studies
using Na-fluorescein and BSA as gavage-fed markers. Less uptake (measured as
plasma concentrations) of the marker molecule Na-fluorescein occurred during a 24
h study period, and numerically lower levels of BSA were observed compared with
studies in control pigs of the same age. A total of 12 pigs (6 control, 6 PHA
treated) were euthanized on the day of weaning for analyses of gastrointestinal
properties. The PHA-treated pigs tended to have a longer total small intestinal
length (P = 0.063) than that of the control pigs. The enzyme profile of the
jejunal epithelium responded to PHA exposure with a decrease in lactase activity
and an increase in maltase and sucrase activities, which is similar to changes
normally observed after weaning. No differences were found in the size of the
pancreas or in its contents of trypsin and amylase. In conclusion, exposing
piglets to crude, red kidney bean lectin for 3 d during the week before weaning
led to changes in performance and small intestinal functional properties that
would be expected to contribute to a more successful weaning.
PMID- 17040949
TI - Ribonucleic acid interference: a new approach to the in vivo study of gene
function.
AB - The definition of hormone function was classically accomplished by ablation
replacement studies. However, as our knowledge of the complexity of hormones and
growth factors has grown, it has become increasingly difficult to clearly define
the necessity and function of many of the hormones, growth factors, and
regulatory proteins under investigation. The use of homologous recombination
within mouse embryonic stem cell lines allows functional gene ablation and has
been used extensively during the past 15 yr to define specific gene function. The
use of similar methodologies in livestock species has yet to yield an efficient
approach. In contrast, the parallel development of our understanding of naturally
occurring RNA interference, along with the development of efficient virus-based
vectors for gene transfer, holds great potential for effectively "knocking down"
specific gene function. Short-hairpin (sh) RNA-encoding cassettes, typically
consisting of inverted repeats separated by a loop sequence and followed by a
short poly(T) string to terminate transcription, are inserted downstream of an
RNA polymerase III promoter within the viral vector of choice. Several viral
vectors are useful for delivery of shRNA expression cassettes, each with
particular attributes. Adenovirus- and lentivirus-derived vectors provide a high
rate of infectivity in most mammalian cell types, with lentiviral vectors
allowing stable integration into the host genome if the study of long-term
effects is needed. Upon transcription, a shRNA is generated, and the loop is
recognized by the processing enzyme Dicer, generating guide sequences. Guide
sequences are incorporated into the RNA-induced silencing complex, which targets
mRNA for degradation if recognized by the guide sequence. For each mRNA of
interest, design and testing of a number of shRNA, along with adequate controls,
are required to identify the most efficient construct before proceeding to in
vivo use. This technology may become the method of choice for defining gene
function in livestock.
PMID- 17040950
TI - Regulation of meiotic maturation.
AB - Mammalian oocytes are arrested at prophase of the first meiotic division before
induction of maturation by the preovulatory LH surge. In vitro, oocyte maturation
occurs spontaneously. The first meiotic arrest is characterized by a large
nucleus called the germinal vesicle. One important signaling molecule for
resumption of meiosis is cyclic AMP (cAMP). High levels of cAMP block spontaneous
meiotic resumption. Research investigating the regulation of oocyte cAMP has led
to the discovery of new receptors, guanosine 5'-triphosphate-binding (G)
proteins, cyclases, and phosphodiesterases. Leydig insulin-like 3, a polypeptide
growth factor of the insulin family, is expressed in thecal cells. Leydig insulin
like 3 activates the Leu-rich, repeat-containing, G protein-coupled receptor 8,
which is expressed in the oocyte. Coupled to the inhibitory GTP binding protein,
this receptor leads to a decrease in cAMP production. Treatment with Leydig
insulin-like 3 polypeptide initiates meiotic progression of oocytes in
preovulatory follicles, demonstrating the importance of cAMP management for
meiotic resumption. Furthermore, microinjection of an antibody against
stimulatory G protein (Gs) into mouse oocytes results in meiotic resumption,
suggesting that meiotic arrest of the oocyte is dependent on Gs activity. The
orphan Gs-linked receptor, GPR3, is expressed in the oocyte. The oocytes of GPR3
null mice resume meiosis when still in their follicles, suggesting that GPR3 is
involved in the control of cAMP production and thus meiotic arrest. Cyclic
nucleotides are synthesized by cyclases and degraded by phosphodiesterases. Mouse
and rat oocytes express isoform 3 of adenylyl cyclase. In the mouse, the null
mutation results in approximately 50% of the oocytes resuming meiosis,
demonstrating the importance of the synthesis of cAMP in controlling nuclear
maturation. The null mutation of the major phosphodiesterase expressed in mouse
oocytes results in female sterility due to ovulation of meiotically arrested
oocytes that cannot be fertilized. Maintenance of meiotic arrest is explained by
constitutive cAMP signaling associated with undetectable cAMP-phosphodiesterase
activity. Collectively, these results are beginning to illuminate the key
signaling molecules involved in the control of intraoocyte cAMP levels, thus
regulating the arrest and resumption of meiosis.
PMID- 17040951
TI - Technical note: preorbital gland opening in red deer (Cervus elaphus) calves as
an indicator of stress.
AB - The opening of the preorbital gland of red deer (Cervus elaphus) calves has been
previously associated with feeding and satiety. However, it has been suggested to
be most likely affected by some other factor or factors, possibly by excitement
of the calf. If so, a calf should open its preorbital gland while being exposed
to any stressful procedure. The hypothesis was tested that the preorbital gland
is closed in a relaxed calf, whereas it is opened in a stressed calf. Preorbital
opening was observed in 41 newborn red deer farm calves during a regular daily
routine consisting of a search for newborn calves, their inspection, weighing,
and painful marking with an ear tag. The openness of the preorbital gland
(preorbital gland closed or opened) was recorded just before manipulation of a
lying calf (i.e., in a calm calf) and then during the manipulation (i.e., in a
distressed calf). Before manipulation, in all but 3 calves (7.3%, all of which
were males), the preorbital gland was closed. All calves observed (100%) opened
their preorbital gland during their manipulation, at least by the time the ear
was punctured by the ear tag. The proportion of individuals with an open gland
was lower (P < 0.001) before than during manipulation (7.3 vs. 100%,
respectively). Hence, openness of the preorbital gland in newborn red deer calves
was associated with a stressful manipulation by the humans, which suggests that
it may be a simple and easily recognized indicator of calf stress.
PMID- 17040952
TI - Why is the fetal allograft not rejected?
AB - In viviparous species, the conceptus must be protected from a potentially hostile
maternal immune system. The major histocompatibility complex (MHC) is a genetic
region that encodes MHC class I and class II proteins, which present peptide
antigens to T lymphocytes and induce graft rejection. The MHC, class II proteins
are only expressed on professional, antigen-presenting cells. However, classical,
MHC class I proteins are expressed on all nucleated somatic cells. Protection of
the conceptus from immune-mediated rejection involves downregulation of classical
MHC class I antigen expression on trophoblast cells, which form the external
epithelial layer of the placenta, and maintenance of an immunologically favorable
immunosuppressive environment in the uterus. Normally, bovine trophoblast cells
do not express MHC class I antigens before d 120 of pregnancy. However, during
the last third of gestation, trophoblast cells in the inter-placentomal and
arcade regions of the placenta express classical, MHC class I proteins, which
could potentially induce fetal rejection, as well as nonclassical, MHC class I
proteins. A human, nonclassical, MHC class I antigen, human leukocyte antigen G,
is an important immunoregulatory factor required for the maintenance of
pregnancy. In cattle, MHC class I expression during the last third of pregnancy
has no adverse effects and probably contributes to placental separation at
parturition. However, somatic cell nuclear transfer (SCNT) conceptuses, the
majority of which are aborted between d 30 and 90 of pregnancy, had trophoblast
cell expression of MHC class I antigens before d 34 of pregnancy. In conjunction
with increased trophoblast MHC class I expression, SCNT pregnancies exhibited a
marked increase in the number of stromal lymphocytes in the uteri of surrogate
dams. A retrospective study found that SCNT pregnancies established using MHC
class I-homozygous cell lines, in which the immunological barrier is greatly
reduced, had significantly improved fetal survival from d 28 to term (51%
survival for MHC-homozygous and 5% for MHC-heterozygous SCNT fetuses).
Consequently, it appears that the high rate of fetal mortality in SCNT
pregnancies is due, at least in part, to inappropriate expression of trophoblast,
MHC class I antigens resulting in immune-mediated placental rejection. This
suggests that appropriate regulation of MHC class I genes is critical for
immunological acceptance of an allogeneic conceptus.
PMID- 17040953
TI - Association of a single nucleotide polymorphism in SPP1 with growth traits and
twinning in a cattle population selected for twinning rate.
AB - Continued validation of genetic markers for economically important traits is
crucial to establishing marker-assisted selection as a tool in the cattle
industry. The objective of the current study was to evaluate the association of a
SNP (T(9)/T(10)) in the osteopontin gene (SPP1) with growth rate in a large
cattle population spanning multiple generations and representing alleles from 12
founding breeds. This population has been maintained at the US Meat Animal
Research Center since 1981 and subjected to selection for twinning rate.
Phenotypic records for this population included twinning rate and ovulation rate,
providing an opportunity to examine the potential effects of SPP1 genotype on
reproductive traits. A set of 2,701 animals was geno-typed for the T(9)/T(10)
polymorphism at SPP1. The geno-typic data, including previously genotyped markers
on chromosome 6 (BTA6), were used in conjunction with pedigree information to
estimate genotypic probabilities for all 14,714 animals with phenotypic records.
The genotypic probabilities for females were used to calculate independent
variables for regressions of additive, dominance, and imprinting effects.
Genotypic regressions were fit as fixed effects in a mixed model analysis, in
which each trait was analyzed in a 2-trait model where single births were treated
as a separate trait from twin births. The association of the SPP1 marker with
birth weight (P < 0.006), weaning weight (P < 0.007), and yearling weight (P <
0.003) was consistent with the previously reported effects of SPP1 genotype on
yearling weight. Our data supports the conclusion that the SNP successfully
tracks functional alleles affecting growth in cattle. The previously undetected
effect of the SNP on birth and weaning weight suggests this particular SPP1
marker may explain a portion of the phenotypic variance explained by QTL for
birth and HCW on BTA6.
PMID- 17040954
TI - Online database for documenting clinical pathology resident education.
AB - BACKGROUND: Training of clinical pathologists is evolving and must now address
the 6 core competencies described by the Accreditation Council for Graduate
Medical Education (ACGME), which include patient care. A substantial portion of
the patient care performed by the clinical pathology resident takes place while
the resident is on call for the laboratory, a practice that provides the resident
with clinical experience and assists the laboratory in providing quality service
to clinicians in the hospital and surrounding community. Documenting the
educational value of these on-call experiences and providing evidence of
competence is difficult for residency directors. An online database of these
calls, entered by residents and reviewed by faculty, would provide a mechanism
for documenting and improving the education of clinical pathology residents.
METHODS: With Microsoft Access we developed an online database that uses active
server pages and secure sockets layer encryption to document calls to the
clinical pathology resident. Using the data collected, we evaluated the efficacy
of 3 interventions aimed at improving resident education. RESULTS: The database
facilitated the documentation of more than 4 700 calls in the first 21 months it
was online, provided archived resident-generated data to assist in serving
clients, and demonstrated that 2 interventions aimed at improving resident
education were successful. CONCLUSIONS: We have developed a secure online
database, accessible from any computer with Internet access, that can be used to
easily document clinical pathology resident education and competency.
PMID- 17040955
TI - Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio
analysis in maternal plasma: Theoretical and empirical considerations.
AB - BACKGROUND: The discovery of cell-free fetal DNA in maternal plasma has opened up
new possibilities for noninvasive prenatal diagnosis. However, the use of
maternal plasma fetal DNA for the direct detection of fetal chromosomal
aneuploidies has not been reported. We postulate that the aneuploidy status of a
fetus could be revealed by an epigenetic allelic ratio approach, i.e., by
analyzing the allelic ratio of a single-base variation present within DNA
molecules exhibiting a placental-specific epigenetic signature in maternal
plasma. METHODS: Placental-derived fetal-specific unmethylated maspin (SERPINB5)
promoter sequences on human chromosome 18 were detectable in placental-maternal
DNA mixtures and in maternal plasma by bisulfite modification followed by
methylation-specific PCR (MSP) and primer extension. The ratios between the
extension products of the 2 alleles were calculated for heterozygous placentas,
placental-maternal blood cell DNA mixtures, and maternal plasma samples. The
allelic ratios were compared between pregnancies carrying trisomy 18 and euploid
fetuses. RESULTS: The epigenetic allelic ratios of all tested trisomy 18 samples
deviated from the reference range obtained from euploid samples (placental DNA,
1.135 to 2.052; placental-maternal DNA mixtures, 1.170 to 1.985; maternal plasma,
0.330 to 3.044; without skew correction on the raw mass spectrometric data). A
theoretical model was established and validated that predicted that a minimum of
200 copies of genomic DNA after bisulfite conversion were required for
distinguishing euploid and aneuploid fetuses with confidence. CONCLUSION:
Epigenetic allelic ratio analysis of maternal plasma DNA represents a promising
approach for noninvasive prenatal diagnosis of fetal chromosomal aneuploidies.
PMID- 17040956
TI - Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin
resistance, and hyperglycemia in humans.
AB - BACKGROUND: Lipocalin-2, a 25-kDa secreted glycoprotein, is a useful biomarker
for early detection of various renal injuries. Because lipocalin-2 is abundantly
expressed in adipose tissue and liver, we investigated its relevance to obesity
related pathologies. METHODS: We used real-time PCR and in-house immunoassays to
quantify the mRNA and serum concentrations of lipocalin-2 in C57BL/KsJ db/db
obese mice and their age- and sex-matched lean littermates. We analyzed the
association between serum lipocalin-2 concentrations and various metabolic and
inflammatory variables in 229 persons (121 men and 108 women) recruited from a
previous cross-sectional study, and we evaluated the effect of the insulin
sensitizing drug rosiglitazone on serum lipocalin-2 concentrations in 32 diabetic
patients (21 men and 11 women). RESULTS: Compared with the lean littermates,
lipocalin-2 mRNA expression in adipose tissue and liver and its circulating
concentrations were significantly increased in db/db diabetic/obese mice (P
<0.001). These changes were normalized after rosiglitazone treatment. In humans,
circulating lipocalin-2 concentrations were positively correlated (P <0.005) with
adiposity, hypertriglyceridemia, hyperglycemia, and the insulin resistance index,
but negatively correlated (P = 0.002) with HDL cholesterol. There was also a
strong positive association between lipocalin-2 concentrations and high
sensitivity C-reactive protein (hs-CRP), independent of age, sex, and adiposity
(P = 0.007). Furthermore, rosiglitazone-mediated decreases in lipocalin-2
concentrations correlated significantly with increases in insulin sensitivity (r
= 0.527; P = 0.002) and decreases in hs-CRP concentrations (r = 0.509; P =
0.003). CONCLUSIONS: Lipocalin-2 is an inflammatory marker closely related to
obesity and its metabolic complications. Measurement of serum lipocalin-2 might
be useful for evaluating the outcomes of various clinical interventions for
obesity-related metabolic and cardiovascular diseases.
PMID- 17040957
TI - Quantification of urinary oxalate by liquid chromatography-tandem mass
spectrometry with online weak anion exchange chromatography.
AB - BACKGROUND: Urinary oxalate is commonly measured with an enzymatic assay that is
specific but requires a manual clean-up step to reduce ascorbic acid
interference. We developed a urinary oxalate assay that uses liquid
chromatography-tandem mass spectrometry (LC-MS/MS) with anion exchange
chromatography and simple sample preparation. METHODS: We added calibrator or
urine sample (10 microL) to 10 microL of (13)C2 oxalate and 400 microL of water
and performed separation on a Waters OASIS WAX column, flow rate 0.6 mL/min, and
then elution for 0.3 min with water containing 2 mmol/L ammonium acetate and 1
mL/L formic acid and for 1.0 min with 750 mL/L methanol containing 20 mL/L
ammonia. We detected multiple reaction monitoring transitions m/z 88.6 > 60.5 and
m/z 90.5 > 61.5 for oxalic acid and 13C2-oxalate, respectively, with a Quattro
micro tandem mass spectrometer in electrospray-negative mode. RESULTS: Oxalate
and 13C2-oxalate eluted at 1.2 min. Mean recovery was 95%, limit of detection 3.0
micromol/L, lower limit of quantification 100.0 micromol/L, linearity to 2212
micromol/L, imprecision <6%, and bias <3% at 166, 880, and 1720 micromol/L.
Oxalate eluted after the main area of ion suppression. Mean response ratios for
urine and aqueous samples, enriched at 200 and 1000 micromol/L, were 3.7% and
5.4%, respectively. No interference was observed from other organic acids.
Passing and Bablock regression analysis comparing the Trinity Biotech enzymatic
reagent set and LC-MS/MS showed LC-MS/MS = 1.06 (enzymatic assay) -21.2, r =
0.964, n = 110. Bland Altman analysis showed general agreement, with a mean bias
of -1.9 mumol/L. CONCLUSION: This LC-MS/MS assay is applicable for quantifying
urinary oxalate excretion.
PMID- 17040958
TI - Measurement of fibrosis marker xylosyltransferase I activity by HPLC electrospray
ionization tandem mass spectrometry.
AB - BACKGROUND: Xylosyltransferase I (XT-I), the key enzyme in the biosynthesis of
glycosaminoglycan chains in proteoglycans, has increased activity in the blood
serum of patients with connective tissue diseases. Therefore, the measurement of
serum XT-I activity is useful to monitor disease activity in these patients.
METHODS: We developed an HPLC electrospray ionization tandem mass spectrometry
method to assay XT-I activity in serum by use of a synthetic peptide (Bio-BIK-F)
as the XT-I substrate. On the basis of XT-I-mediated transfer of D-xylose from
UDP-D-xylose to the synthetic peptide to form Bio-BIK-F-Xyl, we determined XT-I
activity in human serum samples. RESULTS: Multiple calibration curves for the
analysis of Bio-BIK-F-Xyl exhibited consistent linearity and reproducibility in
the range of 0.20-20 mg/L, corresponding to XT-I activity of 1.14-114 mU/L under
assay conditions. The mean (SD, range) XT-I activity values in 30 blood donor
sera were 18.4 (3.0, 8.7-24.8) mU/L. The limit of detection and lower limit of
quantification were 8.5 microg/L (0.05 mU/L) and 163 microg/L Bio-BIK-F-Xyl (0.93
mU/L XT-I activity), respectively. Interassay imprecision (CV) was 5.4%-26.1% in
the range of 0.64 to 129 mU/L, and mean recovery was 107% (range, 96%-129%).
Method comparison with the radiochemical assay showed a moderate correlation (r =
0.79). The Passing-Bablok regression line was: radiochemical assay = 0.045 LC
MS/MS + 0.061 mU/L, S(y/x) = 0.186. CONCLUSIONS: This simple and robust LC-MS/MS
assay permits the rapid and accurate determination of XT-I activity in human
serum.
PMID- 17040959
TI - Quantitative assay of deletion or duplication genotype by capillary
electrophoresis system: Application in Prader-Willi syndrome and Duchenne
muscular dystrophy.
AB - BACKGROUND: Deletions and duplications involving large DNA segments result in
underexpression or overexpression, depending on the changes in allele dose, and
are known to cause many common disorders. Detection of allele dose variations in
the human genome is increasingly important in medical genetic diagnosis. METHODS:
We used multiplex quantitative PCR coupled with capillary electrophoresis for
accurate allele dose determination. In cases of Prader-Willi syndrome (PWS), a
total of 24 patients with PWS, as well as 205 control individuals from the
general population, were analyzed by use of multiplex quantitative PCR to amplify
the FGFR2 gene, the KRIT1 gene, and the SNRPN gene simultaneously. In cases of
Duchenne muscular dystrophy (DMD), we optimized the multiplex quantitative PCR to
amplify 38 exons to analyze the DMD gene for rapid diagnosis of 12 DMD-affected
males, 12 obligate carriers from families, and 50 unaffected female controls.
RESULTS: We were able to unambiguously diagnose the deletion genotype in PWS
patients and identify all deletion or duplication genotypes and carrier status in
DMD-affected cases with 100% sensitivity and specificity. CONCLUSIONS: This
report describes a novel single assay that can rapidly quantify allele dose to
provide accurate clinical genetic diagnosis. This technique offers a valuable
alternative for the rapid detection of genomic deletions or duplications and
decreases costs because it does not require expensive fluorescent reagents.
PMID- 17040960
TI - Sensitive detection of KIT D816V in patients with mastocytosis.
AB - BACKGROUND: The 2447 A > T pathogenic variation at codon 816 of exon 17 (D816V)
in the KIT gene, occurring in systemic mastocytosis (SM), leads to constitutive
activation of tyrosine kinase activity and confers resistance to the tyrosine
kinase inhibitor imatinib mesylate. Thus detection of this variation in SM
patients is important for determining treatment strategy, but because the
population of malignant cells carrying this variation is often small relative to
the normal cell population, standard molecular detection methods can be
unsuccessful. METHODS: We developed 2 methods for detection of KIT D816V in SM
patients. The first uses enriched sequencing of mutant alleles (ESMA) after BsmAI
restriction enzyme digestion, and the second uses an allele-specific competitive
blocker PCR (ACB-PCR) assay. We used these methods to assess 26 patients
undergoing evaluation for SM, 13 of whom had SM meeting WHO classification
criteria (before variation testing), and we compared the results with those
obtained by direct sequencing. RESULTS: The sensitivities of the ESMA and the ACB
PCR assays were 1% and 0.1%, respectively. According to the ACB-PCR assay
results, 65% (17/26) of patients were positive for D816V. Of the 17 positive
cases, only 23.5% (4/17) were detected by direct sequencing. ESMA detected 2
additional exon 17 pathogenic variations, D816Y and D816N, but detected only 12
(70.5%) of the 17 D816V-positive cases. Overall, 100% (15/15) of the WHO
classified SM cases were codon 816 pathogenic variation positive. CONCLUSION:
These findings demonstrate that the ACB-PCR assay combined with ESMA is a rapid
and highly sensitive approach for detection of KIT D816V in SM patients.
PMID- 17040961
TI - Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum.
AB - BACKGROUND: Resistin is a newly identified adipocytokine which has demonstrated
links between obesity and insulin resistance in rodents. In humans,
proinflammatory properties of resistin are superior to its insulin resistance
inducing effects. OBJECTIVES: To assess resistin expression in synovial tissues,
serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis
and spondylarthropathies (SpA), and to study its relationship with inflammatory
status and rheumatoid arthritis disease activity. METHODS: Resistin expression
and localisation in synovial tissue was determined by immunohistochemistry and
confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin
(IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant
protein-1 levels were measured. The clinical activity of patients with rheumatoid
arthritis was assessed according to the 28 joint count Disease Activity Score
(DAS28). RESULTS: Resistin was detected in the synovium in both rheumatoid
arthritis and osteoarthritis. Staining in the sublining layer was more intensive
in patients with rheumatoid arthritis compared with those with osteoarthritis. In
rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells
(CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial
fluid resistin was higher in patients with rheumatoid arthritis than in those
with SpA or osteoarthritis (both p<0.001). In patients with rheumatoid arthritis
and SpA, serum resistin levels were higher than those with osteoarthritis
(p<0.01). Increased serum resistin in patients with rheumatoid arthritis
correlated with both CRP (r=0.53, p<0.02), and DAS28 (r=0.44, p<0.05), but not
with selected (adipo) cytokines. CONCLUSION: The upregulated resistin at local
sites of inflammation and the link between serum resistin, inflammation and
disease activity suggest a role for resistin in the pathogenesis of rheumatoid
arthritis.
PMID- 17040962
TI - High anti-collagen type-II antibody levels and induction of proinflammatory
cytokines by anti-collagen antibody-containing immune complexes in vitro
characterise a distinct rheumatoid arthritis phenotype associated with acute
inflammation at the time of disease onset.
AB - OBJECTIVE: To investigate whether the cytokine-inducing properties of surface
bound collagen type II (CII)-containing immune complexes (IC), which were
reported earlier, have any clinical impact. METHODS: Anti-CII serology was
analysed in 274 patients with early rheumatoid arthritis (RA). Patients with
increased levels of anti-CII were followed serially for 1-5 years with regard to
anti-CII IC-induced levels of tumour necrosis factor (TNF)alpha, interleukin
(IL)1beta and IL8. Levels of antibodies and IC-induced cytokines were compared
with clinical indices over 5 years of follow-up. RESULTS: 5/100 healthy controls
and 24/274 (8.8%) patients with RA exhibited increased levels (>29 arbitrary
units (AU)/ml) of anti-native CII antibodies, a non-significant difference. 9/274
(3.3%) patients with RA and no controls comprised a discrete group with high anti
CII levels>450 AU/ml. These high anti-CII level sera were associated with
induction of pro-inflammatory cytokines by anti-CII-containing IC formed in
vitro. 8/9 patients with high baseline anti-CII levels exhibited a parallel
decline in antibody levels, IC-induced cytokines, C reactive protein (CRP) and
erythrocyte sedimentation rate (ESR). Anti-CII-positive patients had
significantly increased levels of CRP and ESR at baseline, but not later during
the follow-up. CONCLUSIONS: Anti-native CII-positive patients with RA have a
distinct clinical phenotype characterised by an early acute phase response that
might be driven by anti-CII-containing IC in joint cartilage.
PMID- 17040963
TI - Increase of B cell-activating factor of the TNF family (BAFF) after rituximab
treatment: insights into a new regulating system of BAFF production.
AB - BACKGROUND: The cytokine B cell-activating factor of the TNF family (BAFF) is
involved in the pathogenesis of autoimmune diseases. OBJECTIVE: To access changes
in serum protein and mRNA levels of BAFF after rituximab treatment. METHODS:
Serum and peripheral blood mononuclear cells (PBMCs) were isolated from five
patients (two with lupus, two with Sjogren's syndrome, one with rheumatoid
arthritis) before and 12 weeks (range 7-17) after a first course of rituximab
infusion. Monocytes and B cells were selected from healthy controls and
cocultured for 72 h. BAFF protein and mRNA levels were assessed by ELISA and real
time PCR, respectively. RESULTS: After rituximab treatment, median serum BAFF
protein level and BAFF to actin mRNA ratio in PBMCs significantly increased. In
monocytes cocultured with autologous B cells, BAFF protein level decreased,
whereas the mRNA level was stable. In one closely monitored patient, the mRNA
ratio of BAFF to actin in PBMCs increased later than the BAFF serum level.
CONCLUSIONS: Two distinct mechanisms are probably involved in the increase in
BAFF level after B cell depletion: (1) the decrease in its receptors leading to a
release of BAFF; (2) a delayed regulation of BAFF mRNA transcription. This could
favour the re-emergence of autoreactive B cells.
PMID- 17040964
TI - Insulin-like growth factor-I receptors in atherosclerotic plaques of symptomatic
and asymptomatic patients with carotid stenosis: effect of IL-12 and IFN-gamma.
AB - The balance between apoptosis and survival of vascular smooth muscle cells
(VSMCs) in the fibrous cap appears to best correlate with plaque instability or
stability and is controlled by growth factors and cytokines. We recently reported
the inhibition of insulin-like growth factor (IGF)-I-induced proliferation and
increase in apoptosis of VSMCs by atheroma-associated cytokines. Here we assessed
the expression of IGF-I receptor (IGF-IR) in atherosclerotic plaques and in
plaque VSMCs of asymptomatic and symptomatic patients with carotid stenosis and
examined the effect of IGF-I, IL-12, and IFN-gamma on the expression of IGF-IR
and IGF-binding protein (IGFBP)-3 in plaque VSMCs. We observed significantly
lower density of terminal deoxynucleotidyl transferase-mediated dUTP nick-end
labeling-positive apoptotic nuclei and increased positive immunoreactivity to IGF
IR and mRNA transcripts of endogenous IGF-I and IGF-IR in asymptomatic than in
symptomatic plaque VSMCs. Positive correlation was found between apoptosis and
IGF-IR expression in asymptomatic (r(2) = 0.942) and symptomatic (r(2) = 0.908)
plaque VSMCs. The specific binding of (125)I-labeled IGF-I was 3.7-fold higher in
plaque VSMCs of asymptomatic patients than in symptomatic patients. IGF-I
increased both IGF-IR mRNA transcripts and expression of IGFBP-3 in VSMCs of
asymptomatic plaques. IL-12 and IFN-gamma decreased IGF-IR mRNA transcripts and
further increased the expression of IGFBP-3 in asymptomatic VSMCs but had no
effect in symptomatic VSMCs. These data suggest that the decreased expression of
IGF-IR mRNA and increased expression of IGFBP-3 in carotid plaques of symptomatic
patients could be due to atheroma-associated cytokines and this could result in
plaque instability.
PMID- 17040965
TI - Kv1.5 is a major component underlying the A-type potassium current in retinal
arteriolar smooth muscle.
AB - Little is known about the molecular characteristics of the voltage-activated K(+)
(K(v)) channels that underlie the A-type K(+) current in vascular smooth muscle
cells of the systemic circulation. We investigated the molecular identity of the
A-type K(+) current in retinal arteriolar myocytes using patch-clamp techniques,
RT-PCR, immunohistochemistry, and neutralizing antibody studies. The A-type K(+)
current was resistant to the actions of specific inhibitors for K(v)3 and K(v)4
channels but was blocked by the K(v)1 antagonist correolide. No effects were
observed with pharmacological agents against K(v)1.1/2/3/6 and 7 channels, but
the current was partially blocked by riluzole, a K(v)1.4 and K(v)1.5 inhibitor.
The current was not altered by the removal of extracellular K(+) but was
abolished by flecainide, indicative of K(v)1.5 rather than K(v)1.4 channels.
Transcripts encoding K(v)1.5 and not K(v)1.4 were identified in freshly isolated
retinal arterioles. Immunofluorescence labeling confirmed a lack of K(v)1.4
expression and revealed K(v)1.5 to be localized to the plasma membrane of the
arteriolar smooth muscle cells. Anti-K(v)1.5 antibody applied intracellularly
inhibited the A-type K(+) current, whereas anti-K(v)1.4 antibody had no effect.
Co-expression of K(v)1.5 with K(v)beta1 or K(v)beta3 accessory subunits is known
to transform K(v)1.5 currents from delayed rectifers into A-type currents.
K(v)beta1 mRNA expression was detected in retinal arterioles, but K(v)beta3 was
not observed. K(v)beta1 immunofluorescence was detected on the plasma membrane of
retinal arteriolar myocytes. The findings of this study suggest that K(v)1.5,
most likely co-assembled with K(v)beta1 subunits, comprises a major component
underlying the A-type K(+) current in retinal arteriolar smooth muscle cells.
PMID- 17040966
TI - Heart slice NMR.
AB - Nuclear magnetic resonance (NMR) spectroscopy of the heart is normally carried
out using whole heart preparations under coronary perfusion. In such
preparations, either radical changes in ionic composition of the perfusate or
applications of numerous drugs would affect coronary microcirculation. This
report communicates the first (31)P NMR spectroscopy study using a heart slice
preparation (left ventricular slices) superfused with extracellular medium. The
ratio of phosphocreatine concentration to ATP concentration was approximately
2.1. Also, intracellular pH and Mg(2+) concentration ([Mg(2+)](i)), estimated
from the chemical shifts of inorganic phosphate and ATP, were comparable with
those under retrograde perfusion. [Mg(2+)](i) was significantly increased by the
removal of extracellular Na(+), supporting the essential role of Na(+)-coupled
Mg(2+) transport in Mg(2+) homeostasis of the heart. Heart slice preparation
could also be used to evaluate the potency of cardiac drugs, regardless of their
possible effects on coronary microcirculation.
PMID- 17040967
TI - The mechanism of flow-induced dilation in human adipose arterioles involves
hydrogen peroxide during CAD.
AB - Flow-induced dilation (FID) is an important physiological stimulus that regulates
tissue blood flow and is mediated by endothelium-derived factors that play a role
in vascular integrity and the development of atherosclerosis. In coronary artery
disease (CAD), conduit artery FID is impaired. The purpose of this study was to
determine the mechanism of FID in human visceral adipose and examine whether the
presence of conduit coronary atherosclerosis is associated with altered
endothelial function in visceral fat. FID was determined in isolated visceral fat
arterioles from patients with and without CAD. After constriction with endothelin
1, increases in flow produced an endothelium-dependent vasodilation that was
sensitive to N(omega)-nitro-l-arginine methyl ester (l-NAME) in visceral fat
arterioles from patients without CAD. In contrast, l-NAME alone or in combination
with indomethacin had no effect on FID in similarly located arterioles from
patients with CAD. Flow increased dichlorofluorescein (DCF) and dihydroethidium
fluorescence accumulation in arterioles from patients with CAD versus without,
indicative of the production of oxidative metabolites and superoxide,
respectively. Both the dilation and DCF fluorescence to flow were reduced in the
presence of the H(2)O(2) scavenger polyethylene glycol-catalase. Exogenous
H(2)O(2) elicited similar relaxations of arterioles from patients in both groups.
These data indicate that FID in visceral fat arterioles is nitric oxide dependent
in the absence of known CAD. However, in the presence of CAD, H(2)O(2) replaces
nitric oxide as the mediator of endothelium-dependent FID. This study provides
evidence that adverse microvascular changes during CAD are evident in human
visceral adipose, a tissue associated with CAD.
PMID- 17040968
TI - Surface association of pregnancy-associated plasma protein-A accounts for its
colocalization with activated macrophages.
AB - Intense immunostaining for pregnancy-associated plasma protein-A (PAPP-A), a
newly characterized metalloproteinase in the insulin-like growth factor system,
colocalizes with activated macrophages in human atherosclerotic plaque. To
determine macrophage regulation of PAPP-A expression, we developed two models of
human macrophages with basal and activated phenotypes. THP-1 cells and peripheral
blood monocytes could be differentiated into macrophages and activated upon
specific treatment regimens with phorbol myristate acetate, macrophage colony
stimulating factor, and interleukin-1beta. Activation was assessed by cell
secretion of tumor necrosis factor-alpha, which increased 30- to 100-fold with
activation. Activated macrophages also secreted matrix metalloproteinase-9.
However, no PAPP-A mRNA or PAPP-A antigen could be detected in these cells under
any condition. Upon incubation with recombinant PAPP-A, we found that activated
macrophages bound and internalized more PAPP-A than unactivated macrophages or
monocytes. Internalization accounted for at least 50% of macrophage-associated
PAPP-A, as assessed in studies with cytochalasin B. Membrane-bound PAPP-A
retained protease activity, whereas internalized PAPP-A had little or no
activity. Similar experiments carried out with a mutated variant of PAPP-A, which
retains functionality as a protease but is unable to bind surface-associated
glycosaminoglycan, showed no macrophage association or internalization. Absence
of PAPP-A expression was confirmed in activated macrophages isolated from a
hypercholesterolemic rabbit model of atherosclerosis. We therefore conclude that
PAPP-A is not synthesized in, but rather is bound and internalized by,
macrophages. Our findings likely account for the observed intense immunostaining
for PAPP-A colocalizing with activated macrophages and may have physiological
significance in the development of vulnerable plaque.
PMID- 17040969
TI - Adenoviral expression of 15-lipoxygenase-1 in rabbit aortic endothelium: role in
arachidonic acid-induced relaxation.
AB - Endothelium-dependent vasorelaxation of the rabbit aorta is mediated by either
nitric oxide (NO) or arachidonic acid (AA) metabolites from cyclooxygenase (COX)
and 15-lipoxygenase (15-LO) pathways. 15-LO-1 metabolites of AA, 11,12,15
trihydroxyeicosatrienoic acid (THETA), and 15-hydroxy-11,12-epoxyeicosatrienoic
acid (HEETA) cause concentration-dependent relaxation. We tested the hypothesis
that in the 15-LO pathway of AA metabolism, 15-LO-1 is sufficient and is the rate
limiting step in inducing relaxations in rabbit aorta. Aorta and rabbit aortic
endothelial cells were treated with adenoviruses containing human 15-LO-1 cDNA
(Ad-15-LO-1) or beta-galactosidase (Ad-beta-Gal). Ad-15-LO-1-transduction
increased the expression of a 75-kDa protein corresponding to 15-LO-1, detected
by immunoblotting with an anti-human15-LO-1 antibody, and increased the
production of HEETA and THETA from [(14)C]AA. Immunohistochemical studies on Ad
15-LO-1-transduced rabbit aorta showed the presence of 15-LO-1 in endothelial
cells. Ad-15-LO-1-treated aortic rings showed enhanced relaxation to AA (max 31.7
+/- 3.2%) compared with Ad-beta-Gal-treated (max 12.7 +/- 3.2%) or control
nontreated rings (max 13.1 +/- 1.6%) (P < 0.01). The relaxations in Ad-15-LO-1
treated aorta were blocked by the 15-LO inhibitor cinnamyl-3,4-dihydroxy-a
cyanocinnamate. Overexpression of 15-LO-1 in the rabbit aortic endothelium is
sufficient to increase the production of the vasodilatory HEETA and THETA and
enhance the relaxations to AA. This confirms the role of HEETA and THETA as
endothelium-derived relaxing factors.
PMID- 17040970
TI - Extracellular glycerol regulates the cardiac energy balance in a working rat
heart model.
AB - We reported previously that glycerol is a substrate for energy production in
cardiomyocytes. Increasing glycerol availability results in increased glycerol
uptake and its involvement in complex lipid biosynthesis and energy production.
This study evaluated the relationship between glycerol supply, energy demand, and
intermediary metabolism leading to energy production. The work was performed on
isolated rat heart perfused in the working mode. Glycerol concentrations modeled
the fasting (0.33 mM) and fed (3.33 mM) states. Cardiac energy demand was modeled
by increasing heart rate from 350 to 450 beats/min (bpm). Increasing glycerol
supply increased glycerol uptake from 1.4 (350 bpm) to 3.8 (450 bpm) and from 9.7
(350 bpm) to 34.2 (450 bpm) micro mol glycerol/heart in 30 min at 0.33 and 3.33
mM glycerol, respectively. At low glycerol supply, increasing heart rate did not
influence the complex lipid synthesis. Conversely, high glycerol concentration
increased the complex lipid synthesis by 5- and 30-fold at 350 and 450 bpm,
respectively. Increasing glycerol supply and heart rate significantly increased
glycerol oxidation rate. Moreover, increasing glycerol supply did not affect
glucose oxidation but increased palmitate uptake and significantly decreased its
beta-oxidation. Physiological concentrations of glycerol contribute to the
cardiac intermediary metabolism, both for energy production and glycerolipid
synthesis. Increasing energy demand enhances the requirement and use of glycerol.
Glycerol contributes to the regulation of cardiac metabolism and energy balance,
mainly by decreasing the contribution of fatty acid oxidation, and may thus
represent a new factor in cardiac protection through the reduction of oxygen
demand.
PMID- 17040971
TI - Swimming stress in DN 14-3-3 mice triggers maladaptive cardiac remodeling: role
of p38 MAPK.
AB - It is generally believed that a mechanical signal initiates a cascade of
biological events leading to coordinated cardiac remodeling. 14-3-3 family
members are dimeric phosphoserine-binding proteins that regulate signal
transduction, apoptotic, and checkpoint control pathways. To evaluate the
molecular mechanism underlying swimming stress-induced cardiac remodeling, we
examined the role of 14-3-3 protein and MAPK pathway by pharmacological and
genetic means using transgenic mice with cardiac-specific expression of dominant
negative (DN) mutants of 14-3-3 (DN 14-3-3/TG) and p38alpha/beta MAPK (DNp38alpha
and DNp38beta) mice. p38 MAPK activation was earlier, more marked, and longer in
the myocardium of the TG group compared with that of the nontransgenic (NTG)
group after swimming stress, whereas JNK activation was detected on day 5 and
decreased afterward. In contrast, ERK1/2 was not activated after swimming stress
in either group. Cardiomyocyte apoptosis, cardiac hypertrophy, and fibrosis were
greatly increased in the TG group compared with those in the NTG group. Moreover,
we found a significant correlation between p38 MAPK activation and apoptosis in
the TG group. Furthermore, DN 14-3-3 hearts showed enhanced atrial natriuretic
peptide expression. In contrast, DNp38alpha and DNp38beta mice exhibited reduced
mortality and increased resistance to cardiac remodeling after 28 days of
swimming stress compared with TG and NTG mice. Besides, treatment with a p38 MAPK
inhibitor, FR-167653, resulted in regression of cardiac hypertrophy and fibrosis
and improvement in the survival rate in the TG group. These results indicate for
the first time that 14-3-3 protein along with p38 MAPK plays a crucial role in
left ventricular remodeling associated with swimming stress.
PMID- 17040972
TI - P2X purinergic receptor-mediated ionic current in cardiac myocytes of
calsequestrin model of cardiomyopathy: implications for the treatment of heart
failure.
AB - P2X purinergic receptors, activated by extracellular ATP, mediate a number of
cardiac cellular effects and may be important under pathophysiological
conditions. The objective of the present study was to characterize the P2X
receptor-mediated ionic current and determine its role in heart failure using the
calsequestrin (CSQ) model of cardiomyopathy. Membrane currents under voltage
clamp were determined in myocytes from both wild-type (WT) and CSQ mice. The P2X
agonist 2-methylthio-ATP (2-meSATP) induced an inward current that was greater in
magnitude in CSQ than in WT ventricular cells. The novel agonist, MRS-2339, an N
methanocarba derivative of 2-chloro-AMP relatively resistant to nucleotidase,
induced a current in the CSQ myocyte similar to that by 2-meSATP. When
administered via a miniosmotic pump (Alzet), it significantly increased longevity
compared with vehicle-injected mice (log rank test, P = 0.02). The improvement in
survival was associated with decreases in the heart weight-to-body weight ratio
and in cardiac myocyte cross-sectional area [MRS-2339-treated mice: 281 +/- 15.4
(SE) mum(2), n = 6 mice vs. vehicle-treated mice: 358 +/- 27.8 mum(2), n = 6
mice, P < 0.05]. MRS-2339 had no vasodilator effect in mouse aorta ring
preparations, indicating that its salutary effect in heart failure is not because
of any vascular unloading. The cardiac P2X current is upregulated in the CSQ
heart failure myocytes. Chronic administration of a nucleotidase-resistant
agonist confers a beneficial effect in the CSQ model of heart failure, apparently
via an activation of the cardiac P2X receptor. Cardiac P2X receptors represent a
novel and potentially important therapeutic target for the treatment of heart
failure.
PMID- 17040973
TI - Immune suppression prevents renal damage and dysfunction and reduces arterial
pressure in salt-sensitive hypertension.
AB - The goal of this study was to test the hypothesis that renal infiltration of
immune cells in Dahl S rats on increased dietary sodium intake contributes to the
progression of renal damage, decreases in renal hemodynamics, and development of
hypertension. We specifically studied whether anti-immune therapy, using
mycophenolate mofetil (MMF), could help prevent increases in renal NF-kappaB
activation, renal infiltration of monocytes/macrophages, renal damage, decreases
in glomerular filtration rate (GFR) and renal plasma flow, and increases in
arterial pressure. Seventy-four 7-to 8-wk-old Dahl S, Rapp strain rats were
maintained on an 8% Na, 8% Na + MMF (20 mg.kg(-1).day(-1)), 0.3% Na, or 0.3% Na +
MMF diet for 5 wk. Arterial and venous catheters were implanted at day 21. By day
35, renal NF-kappaB in 8% Na rats was 47% higher than in 0.3% Na rats and renal
NF-kappaB was 41% lower in 8% Na + MMF rats compared with the 8% Na group. MMF
treatment significantly decreased renal monocyte/macrophage infiltration and
renal damage and increased GFR and renal plasma flow. In high-NA Dahl S rats mean
arterial pressure increased to 182 +/- 5 mmHg, and MMF reduced this arterial
pressure to 124 +/- 3 mmHg. In summary, in Dahl S rats on high sodium intake,
treatment with MMF decreases renal NF-kappaB and renal monocyte/macrophage
infiltration and improves renal function, lessens renal injury, and decreases
arterial pressure. This suggests that renal infiltration of immune cells is
associated with increased arterial pressure and renal damage and decreasing GFR
and renal plasma flow in Dahl salt-sensitive hypertension.
PMID- 17040975
TI - Oxidative stress of myosin contributes to skeletal muscle dysfunction in rats
with chronic heart failure.
AB - Intrinsic muscle abnormalities affecting skeletal muscle are often reported
during chronic heart failure (CHF). Because myosin is the molecular motor of
force generation, we sought to determine whether its dysfunction contributes to
skeletal muscle weakness in CHF and, if so, to identify the underlying causative
factors. Severe CHF was induced in rats by aortic stenosis. In diaphragm and
soleus muscles, we investigated in vitro mechanical performance, myosin-based
actin filament motility, myosin heavy (MHC) and light (MLC) chain isoform
compositions, MLC integrity, caspase-3 activation, and oxidative damage.
Diaphragm and soleus muscles from CHF exhibited depressed mechanical performance.
Myosin sliding velocities were 16 and 20% slower in CHF than in sham in diaphragm
(1.9 +/- 0.1 vs. 1.6 +/- 0.1 microm/s) and soleus (0.6 +/- 0.1 vs. 0.5 +/- 0.1
microm/s), respectively (each P < 0.05). The ratio of slow-to-fast myosin isoform
did not differ between sham and CHF. Immunoblots with anti-MLC antibodies did not
detect the presence of protein fragments, and no activation of caspase-3 was
evidenced. Immunolabeling revealed oxidative damage in CHF muscles, and MHC was
the main oxidized protein. Lipid peroxidation and expression of oxidized MHC were
significantly higher in CHF than in shams. In vitro myosin exposure to increasing
ONOO(-) concentrations was associated with an increasing amount of oxidized MHC
and a reduced myosin velocity. These data provide experimental evidence that
intrinsic myosin dysfunction occurs in CHF and may be related to oxidative damage
to myosin.
PMID- 17040974
TI - Circulating levels of cytochrome c after resuscitation from cardiac arrest: a
marker of mitochondrial injury and predictor of survival.
AB - Ca(2+) overload and reactive oxygen species can injure mitochondria during
ischemia and reperfusion. We hypothesized that mitochondrial injury occurs during
cardiac resuscitation, causing release of cytochrome c to the cytosol and
bloodstream while activating apoptotic pathways. Plasma cytochrome c was measured
using reverse-phase HPLC and Western immunoblotting in rats subjected to 4 or 8
min of untreated ventricular fibrillation and 8 min of closed-chest resuscitation
followed by 240 min of postresuscitation hemodynamic observation. A sham group
served as control. Plasma cytochrome c rose progressively to levels 10-fold
higher than in sham rats 240 min after resuscitation (P < 0.01), despite reversal
of whole body ischemia (decreases in arterial lactate). Cytochrome c levels were
inversely correlated with left ventricular stroke work (r = -0.40, P = 0.02).
Western immunoblotting of left ventricular tissue demonstrated increased levels
of 17-kDa cleaved caspase-3 fragments in the cytosol. Plasma cytochrome c was
then serially measured in 12 resuscitated rats until the rat died or cytochrome c
returned to baseline. In three survivors, cytochrome c rose slightly to 10), the
two longer peptides (11-ala and 17-ala, but not 7-ala) showed remarkable
enhancement of beta-sheet content and formed fibrils after incubation for 1-2
weeks at room temperature. Fluorescence studies suggested that tyrosyl radicals
produced at high pH cross-linked to form dityrosine, which provided added
stabilization for fibril growth. The kinetic progress curves for fibril
formation, obtained by ThT fluorescence assay, showed exponential increase with
time after an initial quiescent period (lag time) and an eventual saturation
phase, all of which are indicative of a nucleation-controlled polymerization
mechanism for fibrillation. Hierarchical self-assembly of the peptides led to the
formation of striking fractal-shaped growth patterns on substrates, raising the
possibility of designing novel materials using these peptides.
PMID- 17040986
TI - Conformational sampling with implicit solvent models: application to the PHF6
peptide in tau protein.
AB - Implicit solvent models approximate the effects of solvent through a potential of
mean force and therefore make solvated simulations computationally efficient. Yet
despite their computational efficiency, the inherent approximations made by
implicit solvent models can sometimes lead to inaccurate results. To test the
accuracy of a number of popular implicit solvent models, we determined whether
implicit solvent simulations can reproduce the set of potential energy minima
obtained from explicit solvent simulations. For these studies, we focus on a six
residue amino-acid sequence, referred to as the paired helical filament 6 (PHF6),
which may play an important role in the formation of intracellular aggregates in
patients with Alzheimer's disease. Several implicit solvent models form the basis
of this work--two based on the generalized Born formalism, and one based on a
Gaussian solvent-exclusion model. All three implicit solvent models generate
minima that are in good agreement with minima obtained from simulations with
explicit solvent. Moreover, free-energy profiles generated with each implicit
solvent model agree with free-energy profiles obtained with explicit solvent. For
the Gaussian solvent-exclusion model, we demonstrate that a straightforward
ranking of the relative stability of each minimum suggests that the most stable
structure is extended, a result in excellent agreement with the free-energy
profiles. Overall, our data demonstrate that for some peptides like PHF6,
implicit solvent can accurately reproduce the set of local energy minimum arising
from quenched dynamics simulations with explicit solvent. More importantly, all
solvent models predict that PHF6 forms extended beta-structures in solution, a
finding consistent with the notion that PHF6 initiates neurofibrillary tangle
formation in patients with Alzheimer's disease.
PMID- 17040988
TI - Cerulean, Venus, and VenusY67C FRET reference standards.
AB - Forster's resonance energy transfer (FRET) can be used to study protein-protein
interactions in living cells. Numerous methods to measure FRET have been devised
and implemented; however, the accuracy of these methods is unknown, which makes
interpretation of FRET efficiency values difficult if not impossible. This
problem exists due to the lack of standards with known FRET efficiencies that can
be used to validate FRET measurements. The advent of spectral variants of green
fluorescent protein and easy access to cell transfection technology suggests a
simple solution to this problem: the development of genetic constructs with known
FRET efficiencies that can be replicated with high fidelity and freely
distributed. In this study, fluorescent protein constructs with progressively
larger separation distances between donors and acceptors were generated and FRET
efficiencies were measured using fluorescence lifetime spectroscopy, sensitized
acceptor emission, and spectral imaging. Since the results from each method were
in good agreement, the FRET efficiency value of each construct could be
determined with high accuracy and precision, thereby justifying their use as
standards.
PMID- 17040987
TI - Enhanced surfactant adsorption via polymer depletion forces: a simple model for
reversing surfactant inhibition in acute respiratory distress syndrome.
AB - Lung surfactant adsorption to an air-water interface is strongly inhibited by an
energy barrier imposed by the competitive adsorption of albumin and other surface
active serum proteins that are present in the lung during acute respiratory
distress syndrome. This reduction in surfactant adsorption results in an
increased surface tension in the lung and an increase in the work of breathing.
The reduction in surfactant adsorption is quantitatively described using a
variation of the classical Smolukowski analysis of colloid stability. Albumin
adsorbed to the interface induces an energy barrier to surfactant diffusion of
order 5 k(B)T, leading to a reduction in adsorption equivalent to reducing the
surfactant concentration by a factor of 100. Adding hydrophilic, nonadsorbing
polymers such as polyethylene glycol to the subphase provides a depletion
attraction between the surfactant aggregates and the interface that eliminates
the energy barrier. Surfactant adsorption increases exponentially with polymer
concentration as predicted by the simple Asakura and Oosawa model of depletion
attraction. Depletion forces can likely be used to overcome barriers to
adsorption at a variety of liquid-vapor and solid-liquid interfaces.
PMID- 17040989
TI - Metastable mesoscopic clusters in solutions of sickle-cell hemoglobin.
AB - Sickle cell hemoglobin (HbS) is a mutant, whose polymerization while in deoxy
state in the venous circulation underlies the debilitating sickle cell anemia. It
has been suggested that the nucleation of the HbS polymers occurs within clusters
of dense liquid, existing in HbS solutions. We use dynamic light scattering with
solutions of deoxy-HbS, and, for comparison, of oxy-HbS and oxy-normal adult
hemoglobin, HbA. We show that solutions of all three Hb variants contain clusters
of dense liquid, several hundred nanometers in size, which are metastable with
respect to the Hb solutions. The clusters form within a few seconds after
solution preparation and their sizes and numbers remain relatively steady for up
to 3 h. The lower bound of the cluster lifetime is 15 ms. The clusters exist in
broad temperature and Hb concentration ranges, and occupy 10(-5)-10(-2) of the
solution volume. The results on the cluster properties can serve as test data for
a potential future microscopic theory of cluster stability and kinetics. More
importantly, if the clusters are a part of the nucleation mechanism of HbS
polymers, the rate of HbS polymerization can be controlled by varying the cluster
properties.
PMID- 17040990
TI - Structural features of parathyroid hormone receptor coupled to Galpha(s)-protein.
AB - The molecular basis of the activation of G-proteins by the G-protein coupled
receptor for parathyroid hormone (PTH) is unknown. Employing a combination of NMR
methods and computer-based structural refinement, structural features involved in
the activation of Galpha(s) by the PTH receptor (PTH1R) have been determined.
Focusing on the C-terminus of the third intracellular loop (IC3), previously
shown to be important for Galpha(s) activation by PTH1R, the structure of this
region, PTH1R(402-408), while bound to Galpha(s), was determined by transferred
nuclear Overhauser effect spectroscopy. The relative topological orientation of
the IC3 while associated with Galpha(s) was determined by saturation transfer
difference spectroscopy. These experimental data were incorporated into molecular
dynamics simulations of the PTH1R and Galpha(s) to provide atomic insight into
the receptor-protein interactions important for PTH signaling and a structural
framework to analyze previous mutagenesis studies of Galpha(s). These data
provide the first step toward development of a molecular mechanism for the
signaling profile of PTH1R, an important regulator of calcium levels in the
bloodstream.
PMID- 17040991
TI - The gas-phase absorption spectrum of a neutral GFP model chromophore.
AB - We have studied the gas-phase absorption properties of the green fluorescent
protein (GFP) chromophore in its neutral (protonated) charge state in a heavy-ion
storage ring. To accomplish this we synthesized a new molecular chromophore with
a charged NH(3) group attached to a neutral model chromophore of GFP. The gas
phase absorption cross section of this chromophore molecule as a function of the
wavelength is compared to the well-known absorption profile of GFP. The
chromophore has a maximum absorption at 415 +/- 5 nm. When corrected for the
presence of the charged group attached to the GFP model chromophore, the
unperturbed neutral chromophore is predicted to have an absorption maximum at 399
nm in vacuum. This is very close to the corresponding absorption peak of the
protein at 397 nm. Together with previous data obtained with an anionic GFP model
chromophore, the present data show that the absorption of GFP is primarily
determined by intrinsic chromophore properties. In other words, there is strong
experimental evidence that, in terms of absorption, the conditions in the
hydrophobic interior of this protein are very close to those in vacuum.
PMID- 17040993
TI - A prospective study of anaemia and long-term outcomes in kidney transplant
recipients.
AB - BACKGROUND: Anaemia is prevalent in kidney transplant recipients (KTR), and only
few KTR with anaemia receive treatment with erythropoietin. Some have claimed
that this undertreatment might contribute to suboptimal outcomes such as
mortality and cardiovascular events in these patients. However, no evidence is
currently available that anaemia is actually associated with such risks in KTR.
METHODS: We merged two cohorts of KTR to study the associations between anaemia
and two outcomes: all-cause mortality and kidney allograft loss. Detailed
information on the demographic and clinical characteristics of these 825 patients
was available at baseline. As recommended by the American Society of
Transplantation, anaemia was considered present if the haemoglobin concentration
was < or =13 g/dl in men or < or =12 g/dl in women. Patients were followed using
the Austrian Dialysis and Transplant Registry. RESULTS: After 8.2 years of follow
up, 251 patients died and 401 allografts were lost. In multivariate analyses,
anaemia was not associated with all-cause mortality (HR: 1.08; 95% CI: 0.80
1.45), but it was associated with 25% greater risk of allograft loss (HR = 1.25;
95% CI: 1.02-1.59). This association was even more pronounced in death-censored
analyses. Analyses using haemoglobin as a continuous variable or in categories
also found no association with mortality. CONCLUSIONS: Anaemia may not be
associated with mortality in KTR. In light of the recent findings of increased
mortality in chronic kidney disease patients with higher haemoglobin treatment
target, further evidence is needed to guide clinicians in the treatment of
anaemia in these patients.
PMID- 17040992
TI - A mathematical model of glioblastoma tumor spheroid invasion in a three
dimensional in vitro experiment.
AB - Glioblastoma, the most malignant form of brain cancer, is responsible for 23% of
primary brain tumors and has extremely poor outcome. Confounding the clinical
management of glioblastomas is the extreme local invasiveness of these cancer
cells. The mechanisms that govern invasion are poorly understood. To gain insight
into glioblastoma invasion, we conducted experiments on the patterns of growth
and dispersion of U87 glioblastoma tumor spheroids in a three-dimensional
collagen gel. We studied two different cell lines, one with a mutation to the
EGFR (U87DeltaEGFR) that is associated with increased malignancy, and one with an
endogenous (wild-type) receptor (U87WT). We developed a continuum mathematical
model of the dispersion behaviors with the aim of identifying and characterizing
discrete cellular mechanisms underlying invasive cell motility. The mathematical
model quantitatively reproduces the experimental data, and indicates that the
U87WT invasive cells have a stronger directional motility bias away from the
spheroid center as well as a faster rate of cell shedding compared to the
U87DeltaEGFR cells. The model suggests that differences in tumor cell dispersion
may be due to differences in the chemical factors produced by cells, differences
in how the two cell lines remodel the gel, or different cell-cell adhesion
characteristics.
PMID- 17040994
TI - Markers of bone turnover in haemodialysis patients.
PMID- 17040995
TI - P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte
free radical production.
AB - BACKGROUND: Chronic renal insufficiency is associated with the retention of
solutes normally excreted by healthy kidneys. P-cresol, a prototype protein-bound
uraemic retention solute, has been shown to exert toxic effects in vitro.
Recently, however, it has been demonstrated that p-cresol in the human body is
conjugated, with p-cresylsulphate as the main metabolite. METHODS: The present
study evaluates the effect of p-cresylsulphate on the respiratory burst activity
of leucocytes. RESULTS: P-cresylsulphate significantly increased the percentage
of leucocytes displaying oxidative burst activity at baseline. Oxidative burst
activity of stimulated leucocytes was however not affected. In contrast, p-cresol
had no effect on the leucocytes at baseline, but inhibited leucocytes burst
activity after stimulation. CONCLUSION: The present study demonstrates, for the
first time, that p-cresylsulphate, the main in vivo metabolite of p-cresol, has a
pro-inflammatory effect on unstimulated leucocytes. This effect could contribute
to the propensity to vascular disease in the uraemic population.
PMID- 17040996
TI - A nationwide blood spot screening study for Fabry disease in the Czech Republic
haemodialysis patient population.
AB - BACKGROUND: Fabry disease (FD) is a genetic disorder characterized by
accumulation of trihexosylceramide in lysosomes of various tissues leading to
multiorgan manifestations, including progressive renal disease. Previous
screening studies have shown that a non-neglectable proportion of
haemodialysis(HD) patients have unsuspected FD. An extensive FD screening study,
the largest to date, has been conducted in HD patients in Czech Republic. We
aimed to uncover previously undiagnosed FD patients, to enable them to benefit
from cause-specific therapeutic intervention with enzyme replacement therapy
(ERT). METHODS: Large-scale screening was executed using a convenient automated
enzymatic (alpha-galactosidose A, alpha-Gal A) dried blood spot on filter paper
fluorescence method. RESULTS: In total, 3370 (45.1% males, 54.9% females) out of
4058 HD patients (83%) in Czech Republic participated in this blood spot
screening (BSS) study. Abnormal low fluorescence readings were obtained in 117
patients (3.5%). Subsequent determination of plasma alpha-Gal A activity
identified four males and three females with deficient plasma enzyme activity.
Determination of alpha-Gal A activity in peripheral blood leucocytes and
confirmatory molecular analysis resulted in four newly diagnosed Fabry males and
one female. Subsequent family screening identified 10 family members with
genotypically proven FD. Based on these screening results, ERT could be offered
to five male FD patients. CONCLUSIONS: BSS represents a promising screening tool
that has proven to be convenient and effective in uncovering unrecognized FD
patients among the chronic HD population in Czech Republic.
PMID- 17040997
TI - Increased expression of the pro-apoptotic ATP-sensitive P2X7 receptor in
experimental and human glomerulonephritis.
AB - BACKGROUND: The involvement of IL-1beta and other pro-inflammatory cytokines in
most forms of glomerulonephritis is now well established. The P2X(7) receptor, an
ATP-sensitive P2X receptor, functions not only as a non-selective cation channel,
but it is also involved in the rapid processing and release of IL-1beta,
apoptosis and necrotic cell death. Therefore, we wanted to investigate if
expression of this receptor is altered in the glomeruli of rodent models of
glomerulonephritis. METHODS: P2X(7) receptor protein expression was investigated
using immunohistochemistry, and apoptosis was assessed using the TUNEL assay and
caspase-3 immunostaining. Real-time PCR with gene-specific primers was used to
detect P2X(7), IL-1beta, p53, bax and bcl-2 mRNA expression. RESULTS: Although
the levels of the P2X(7) receptor protein in mouse kidney are normally very low,
or undetectable, we detected an increase in glomerular expression of this
receptor and an increase in glomerular apoptotic cells in a mouse model of
accelerated nephrotoxic nephritis. We also observed increased glomerular and
tubular expression of the P2X(7) receptor protein in renal biopsy tissue of
patients with autoimmune-related glomerulonephritis. Furthermore, P2X(7) receptor
mRNA increased in the kidneys of a rat model of proliferative glomerulonephritis
and this coincided with the onset of proteinuria. We also observed increased mRNA
expression of Il-1beta and the pro-apoptotic markers p53 and bax, but not of anti
apoptotic bcl-2. CONCLUSION: Although there is an association between expression
of the pro-inflammatory and pro-apoptotic P2X(7) receptor and glomerulonephritis
in these rodent models, and in at least one form of human glomerulonephritis, the
underlying relationship and its functional significance remain to be explored.
PMID- 17040998
TI - Kidney biopsy in myeloma.
PMID- 17040999
TI - Which cardiovascular risk factors matter in chronic kidney disease?
PMID- 17041000
TI - Mitomycin- and calcineurin-associated HUS, endothelial dysfunction and
endothelial repair: a new paradigm for the puzzle?
PMID- 17041001
TI - Effect of risedronate on high-dose corticosteroid-induced bone loss in patients
with glomerular disease.
AB - BACKGROUND: Corticosteroids are often used for the treatment of glomerular
diseases. We examined whether bisphosphonate or vitamin D3 has beneficial effects
on bone mineral density (BMD) in patients with glomerular diseases being treated
with high-dose corticosteroids, including pulse therapy. METHODS: Thirty-eight
patients (19 men and 19 women, aged 42 +/- 16 years) were randomized into three
groups: bisphosphonate alone (risedronate 2.5 mg/day, group R, n = 12), vitamin
D3 alone (alfacalcidol 0.5 mug/day, group A, n = 15) and the combination of both
agents (group R+A, n = 11). BMD at the lumbar spine was measured before and 12
months after treatment. The biochemical parameters of bone metabolism were
assessed before and 3, 6 and 12 months after treatment. RESULTS: In group R+A,
BMD was significantly increased (+2.0%), whereas BMD was significantly decreased
in group A (-5.6%). The BMD in group R did not show a significant change. In
patients treated with steroid-pulse, BMD was decreased in groups R and A. In
group R+A, BMD was significantly increased (+2.1%). Serum osteocalcin and
alkaline phosphatase levels, markers of bone formation, were significantly
decreased in all groups. Urinary crosslinked N-telopeptide of type I collagen
(NTx) levels, a marker of bone resorption, were decreased in groups R and R+A. In
patients with decreased BMD, the urinary NTx levels at baseline were
significantly higher than the patients with increased BMD. CONCLUSIONS:
Bisphosphonate might be beneficial for the prevention of steroid-induced bone
loss in patients with glomerular diseases compared with vitamin D3. The combined
therapy may be more effective, especially in patients treated with high-dose
corticosteroids, including pulse therapy. A high urinary NTx level before
receiving corticosteroids might be a predictive marker of the loss of BMD.
PMID- 17041002
TI - Interview with Dr. Maurizio C. Capogrossi regarding pivotal advance: high
mobility group box 1 protein--a cytokine with a role in cardiac repair. Interview
by Helene F. Rosenberg and Joost J Oppenheim.
PMID- 17041003
TI - Aggravation of intestinal inflammation by depletion/deficiency of gammadelta T
cells in different types of IBD animal models.
AB - The role of gammadelta T cells in inflammatory bowel disease (IBD) is still
controversial. Although gammadelta T cells induce IBD in immunodeficient animals,
others suggest a protective role of gammadelta T cells. Therefore, this study was
conducted in order to elucidate the effect of gammadelta T cell
depletion/deficiency on different IBD animal models. Mice depleted of or
deficient in gammadelta T cells were exposed to dextran sodium sulfate (DSS) in
order to induce colitis. In addition, gammadelta T cells were depleted in mice
with terminal ileitis (TNFDeltaARE) or colitis due to interleukin 2 deficiency
(IL-2 ko). Finally, DSS-induced colitis was studied in mice deficient in
interferon gamma (IFN-gamma ko) upon gammadelta T cell depletion. Depletion of
gammadelta T cells aggravated DSS-induced colitis and terminal ileitis of
TNFDeltaARE mice. Exacerbated DSS-induced colitis was also found in gammadelta T
cell-deficient mice. IL-2 ko mice showed increased mortality upon early (starting
at 4 wk of age) but not late depletion (starting at 8 wk of age). Early
gammadelta T cell depletion or deficiency resulted in increased IFN-gamma
production by both lamina propria lymphocytes and splenocytes in every model
investigated herein. In IFN-gamma ko mice, gammadelta T cell depletion did not
affect the development and course of DSS-induced colitis. The protective effect
of gammadelta T cells in IBD was confirmed in various IBD animal models.
Particularly, during the early phase of intestinal inflammation, gammadelta T
cells appear to be important. The mechanism seems to involve the control of IFN
gamma production and epithelial regeneration.
PMID- 17041004
TI - The melanocortin system in leukocyte biology.
AB - The melanocortin system is composed of the melanocortin peptides,
adrenocorticotropic hormone and alpha-, beta-, and gamma-melanocyte-stimulating
hormone, the melanocortin receptors (MCRs), and the endogenous antagonists agouti
and agouti-related protein. Melanocortin peptides exert multiple effects upon
the host, including anti-inflammatory and immunomodulatory effects. Leukocytes
are a source of melanocortins and a major target for these peptides. Because of
reduced translocation of the nuclear factor NF-kappaB to the nucleus, MCR
activation by their ligands causes a collective reduction of the most important
molecules involved in the inflammatory process. This review examines how
melanocortin peptides and their receptors participate in leukocyte biology.
PMID- 17041005
TI - Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by
cannabinoids.
AB - Effects of cannabinoids (CBs) are mediated by two types of receptors, CB1 and
CB2. In this report, we investigated whether CBs regulate gene expression of
their cognate receptors in T cells and studied underlying mechanisms in CD4+
Jurkat T cells. Transcription of the CB1 gene was strongly induced in response to
Delta9-tetrahydrocannabinol (THC), whereas the CB2 gene was not regulated. The
induction of CB1 gene expression is mediated by CB2 receptors only, as
demonstrated by using the CB1 and CB2 agonists R(+)-methanandamide and JWH 015,
respectively, and combinations of THC plus CB1- and CB2-specific antagonists.
After activation of CB2 receptors, the transcription factor STAT5 is
phosphorylated. STAT5 then transactivates IL-4. Induction of IL-4 mRNA as well as
IL-4 protein release from the cells are necessary for the following induction of
the CB1 gene. This was demonstrated by using decoy oligonucleotides against
STAT5, which blocked IL-4 and CB1 mRNA induction, and by using the IL-4 receptor
antagonist IL-4 [R121D,Y124D], which blocked the up-regulation of CB1 gene
transcription. Transactivation of the CB1 gene in response to IL-4 is then
mediated by the transcription factor STAT6, as shown by using decoy
oligonucleotides against STAT6. An increase in CB1-mediated phosphorylation of
MAPK in cells prestimulated with CB2-specific agonists suggests up-regulation of
functional CB1 receptor proteins. In summary, up-regulation of CB1 in T
lymphocytes in response to CBs themselves may facilitate or enhance the various
immunomodulatory effects related to CBs.
PMID- 17041006
TI - A p38alpha selective mitogen-activated protein kinase inhibitor prevents
periodontal bone loss.
AB - In the oral microbial environment, Gram-negative bacterial derived
lipopolysaccharide (LPS) can initiate inflammatory bone loss as seen in
periodontal diseases. p38 Mitogen-activated protein kinase (MAPK) signaling is
critical to inflammatory cytokine and LPS-induced cytokine expression, which may
contribute toward periodontal bone loss. The purpose of this proof-of-principle
study was to evaluate the ability of an orally active p38alpha MAPK inhibitor (SD
282) to reduce periopathogenic LPS-induced alveolar bone loss in an experimental
rat model. Five groups of Sprague-Dawley rats received one of the following
treatments: LPS injected to the palatal gingiva adjacent to the maxillary molars
three times per week for 8 weeks, LPS plus two doses of SD-282 (15 or 45 mg/kg)
twice daily by oral gavage, or control groups given drug vehicle (1% polyethylene
glycol) or SD-282 (45 mg/kg) only. Baseline and 8-week alveolar bone loss was
assessed by microcomputed tomography (microCT) and histological examination. LPS
induced severe bone loss over this time period, whereas control groups were
unchanged from baseline measurements. Both doses of SD-282 showed significant
protection from LPS-induced bone loss. Bone area and volumetric analysis of
maxillas by microCT indicated significant loss of bone volume with LPS treatment,
which was blocked with the p38 inhibitor. Histological examination indicated
significantly fewer tartate-resistant acid phosphatase-positive osteoclasts and a
significant decrease in interleukin (IL)-6, IL-1beta, and tumor necrosis factor
alpha expression in p38 inhibitor-treated groups compared with LPS groups by
immunostaining. Results from this in vivo study suggest that orally active p38
MAPK inhibitors can reduce LPS-induced inflammatory cytokine production and
osteoclast formation and protect against LPS-stimulated alveolar bone loss.
PMID- 17041007
TI - Nicotinic regulation of calcium/calmodulin-dependent protein kinase II activation
in the spinal cord.
AB - Recent studies have implicated the involvement of Ca2+-dependent mechanisms, in
particular, calcium/calmodulin-protein kinase II in nicotine-induced
antinociception using the tail-flick test. The spinal cord was suggested as a
possible site of this involvement. The present study was undertaken to
investigate the hypothesis that the beta2 nicotinic receptor subunit plays a
central role in nicotine-induced spinal antinociception via calcium/calmodulin
dependent calmodulin protein kinase II activation. The antinociceptive effects of
i.t. nicotine in the tail-flick test did not significantly differ in wild-type
and alpha7 knockout (KO) animals but were lost in beta2 knockout mice. When
calcium/calmodulin-dependent calmodulin protein kinase II activity in the lumbar
spinal cord after acute i.t. administration of nicotine was investigated in wild
type and beta2 and alpha7 knockout mice, the increase in calcium/calmodulin
dependent calmodulin protein kinase II activity was not significant reduced in
alpha7 KO mice but was eliminated in the beta2 KO mice. In addition, L-type
calcium channel blockers nimodipine and verapamil but not the N-methyl-D
aspartate antagonist MK-801 (dizocilpine maleate) blocked the increase in the
kinase activity induced by nicotine. Taken together, these results are consistent
with the hypothesis that increases in intracellular calcium result in activation
of calcium-mediated second messengers in the spinal cord that play an important
role in nicotine-induced antinociception as measured in the tail-flick test.
Furthermore, our findings indicate that nicotinic stimulation of beta2-containing
acetylcholine nicotinic receptors in the spinal cord can activate
calcium/calmodulin-dependent calmodulin protein kinase II and produce nicotinic
analgesia, which may require L-type calcium voltage and gated channels but not
the intervention of glutamatergic transmission.
PMID- 17041008
TI - Relative activation of human pregnane X receptor versus constitutive androstane
receptor defines distinct classes of CYP2B6 and CYP3A4 inducers.
AB - Both the human pregnane X receptor (hPXR) and constitutive androstane receptor
(hCAR) are capable of regulating CYP3A4 and CYP2B6 gene expression. However, the
majority of currently identified CYP3A4 and CYP2B6 inducers are confirmed
activators of hPXR but not hCAR. To compare these receptors with respect to their
chemical selectivities, 16 drugs known to induce CYP3A4 and/or CYP2B expression
were evaluated for relative activation of hPXR versus hCAR. Because of the high
basal but low chemical-induced activation of hCAR in immortalized cells,
alternative methods were used to evaluate hCAR activation potential. Thirteen of
the 16 compounds were classified as moderate to strong hPXR activators. In
contrast, carbamazepine (CMZ), efavirenz (EFV), and nevirapine (NVP) were
classified as negligible or weak hPXR activators at concentrations associated
with efficacious CYP2B6 reporter or endogenous gene induction in primary human
hepatocytes, suggesting potential activation of hCAR. Subsequent experiments
demonstrated that these three drugs efficiently induced nuclear accumulation of
in vivo-transfected enhanced yellow fluorescent protein-hCAR and significantly
increased expression of a CYP2B6 reporter gene when hCAR was expressed in CAR-/-
mice. In addition, using a recently identified, chemically responsive splice
variant of hCAR (hCAR3), the hCAR activation profiles of the 16 compounds were
evaluated. By combining results from the hPXR- and hCAR3-based reporter gene
assays, these inducers were classified as hPXR, hCAR, or hPXR/hCAR dual
activators. Our results demonstrate that CMZ, EFV, and NVP induce CYP2B6 and
CYP3A4 preferentially through hCAR and that hCAR3 represents a sensitive tool for
in vitro prediction of chemical-mediated human CAR activation.
PMID- 17041009
TI - Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2
on human eosinophils and basophils.
AB - Prostaglandin (PG) D2 acts through both the DP(1) receptor, which is coupled to
adenylyl cyclase, and the DP2 receptor (chemoattractant receptor-homologous
molecule expressed on Th2 cells), which is present on eosinophils, basophils, and
Th2 cells and results in cell activation and migration. The most potent
prostanoid DP2 agonist so far reported is 15R-methyl-PGD2, in which the hydroxyl
group has the unnatural R configuration. In contrast, the corresponding analog
possessing the natural 15S configuration is approximately 75 times less potent.
This raised the question of whether the isoprostane 15R-PGD2 might have potent
DP2 receptor-mediated biological activity. We therefore chemically synthesized
15R-PGD2 and investigated its biological activity. This compound elicited DP2
receptor-mediated CD11b expression in human basophils and eosinophils and induced
actin polymerization and migration in eosinophils with a potency about the same
as that of PGD2. In contrast, it had only a weak effect on DP1 receptor-mediated
adenylyl cyclase activity in human platelets. We also investigated the effects of
modification of the 9-hydroxyl and 11-oxo groups of PGD2. Both PGK2, in which the
9-hydroxyl group is replaced by an oxo group, and 11-deoxy-11-methylene PGD2, in
which the 11-oxo group is replaced by a CH2 group, have little or no DP1 or DP2
agonist activity. However, the 11-methylene analog is a DP2 antagonist (IC50,
approximately 2 microM). We conclude that 15R-PGD2, which may be generated by
oxidative stress, is a potent and selective DP2 agonist and that modification of
the 11-oxo group of PGD2 can result in DP2 antagonist activity.
PMID- 17041010
TI - Sleep-disordered breathing in overweight and obese children and adolescents:
prevalence, characteristics and the role of fat distribution.
AB - AIMS: To determine the prevalence of sleep-disordered breathing (SDB) in a
clinical sample of overweight and obese children and adolescents, and to examine
the contribution of fat distribution. METHODS: Consecutive subjects without
chronic lung disease, neuromuscular disease, laryngomalacia, or any genetic or
craniofacial syndrome were recruited. All underwent measurements of neck and
waist circumference, waist-to-hip ratio, % fat mass and polysomnography.
Obstructive apnoea index > or =1 or obstructive apnoea-hypopnoea index (OAHI) >
or =2, further classified as mild (2< or =OAHI<5) or moderate-to-severe (OAHI> or
=5), were used as diagnostic criteria for obstructive sleep apnoea (OSA). Central
sleep apnoea was diagnosed when central apnoeas/hypopnoeas > or =10 s were
present accompanied by >1 age-specific bradytachycardia and/or >1 desaturation
<89%. Subjects with desaturation < or =85% after central events of any duration
were also diagnosed with central sleep apnoea. Primary snoring was diagnosed
when: snoring was detected by microphone and normal obstructive indices and
saturation. RESULTS: 27 overweight and 64 obese subjects were included (40 boys;
mean (standard deviation (SD)) age 11.2 (2.6) years). Among the obese children,
53% were normal, 11% had primary snoring, 11% had mild OSA, 8% had moderate-to
severe OSA and 17% had central sleep apnoea. Half of the patients with central
sleep apnoea had desaturation <85%. Only enlarged tonsils were predictive of
moderate-to-severe OSA. On the other hand, higher levels of abdominal obesity and
fat mass were associated with central sleep apnoea. CONCLUSION: SDB is very
common in this clinical sample of overweight children. OSA is not associated with
abdominal obesity. On the contrary, higher levels of abdominal obesity and fat
mass are associated with central sleep apnoea.
PMID- 17041011
TI - Tachykinin-1 receptor stimulates proinflammatory gene expression in lung
epithelial cells through activation of NF-kappaB via a G(q)-dependent pathway.
AB - The respiratory tract is innervated by irritant-responsive sensory nerves, which,
on stimulation, release tachykinin neuropeptides in the lung. Tachykinins
modulate inflammatory responses to injury by binding to tachykinin (neurokinin)
receptors present on various pulmonary cell types. In the present study, the
activation of the proinflammatory transcription factor NF-kappaB in lung
epithelial cells was investigated as a mechanism by which tachykinins stimulate
inflammatory processes. In A549 human lung epithelial cells transfected with the
tachykinin-1 receptor (Tacr1), treatment with the Tacr1 ligand substance P (SP)
resulted in NF-kappaB activation, as judged by transcription of an NF-kappaB
luciferase reporter gene and production of interleukin-8, a chemokine whose
expression is upregulated by NF-kappaB. SP caused a dose-dependent activation of
NF-kappaB that was inhibited by the selective Tacr1 antagonist RP67580. Tacr1 is
a G protein-coupled receptor capable of activating both the G(q) and G(s)
families of G proteins. Expression of inhibitory peptides and constitutively
active G protein mutants revealed that G(q) signaling was both necessary for
Tacr1-induced NF-kappaB activation and sufficient for NF-kappaB activation in the
absence of any other treatment. Treatment with pharmacological inhibitors to
investigate events downstream of G(q) revealed that Tacr1-induced NF-kappaB
activation proceeded through an intracellular signaling pathway that was
dependent on phospholipase C, calcium, Ras, Raf-1, MEK, Erk, and proteasome
function. These results identify intracellular signaling mechanisms that underlie
the proinflammatory effects of tachykinins, which previously have been implicated
in lung injury and disease.
PMID- 17041012
TI - Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via
RelA/p65 NF-kappaB in macrophages in vitro and in rat lungs in vivo: implications
for chronic inflammation and aging.
AB - The silent information regulator 2 (Sir2) family of proteins (sirtuins or SIRTs),
which belong to class III histone/protein deacetylases, have been implicated in
calorie restriction, aging, and inflammation. We hypothesized that cigarette
smoke-mediated proinflammatory cytokine release is regulated by SIRT1 by its
interaction with NF-kappaB in a monocyte-macrophage cell line (MonoMac6) and in
inflammatory cells of rat lungs. Cigarette smoke extract (CSE) exposure to
MonoMac6 cells caused dose- and time-dependent decreases in SIRT1 activity and
levels, which was concomitant to increased NF-kappaB-dependent proinflammatory
mediator release. Similar decrements in SIRT1 were also observed in inflammatory
cells in the lungs of rats exposed to cigarette smoke as well as with increased
levels of several NF-kappaB-dependent proinflammatory mediators in
bronchoalveolar lavage fluid and in lungs. Sirtinol, an inhibitor of SIRT1,
augmented, whereas resveratrol, an activator of SIRT1, inhibited CSE-mediated
proinflammatory cytokine release. CSE-mediated inhibition of SIRT1 was associated
with increased NF-kappaB levels. Furthermore, we showed that SIRT1 interacts with
the RelA/p65 subunit of NF-kappaB, which was disrupted by cigarette smoke,
leading to increased acetylation RelA/p65 in MonoMac6 cells. Thus our data show
that SIRT1 regulates cigarette smoke-mediated proinflammatory mediator release
via NF-kappaB, implicating a role of SIRT1 in sustained inflammation and aging of
the lungs.
PMID- 17041013
TI - Exploring host-pathogen interactions at the epithelial surface: application of
transcriptomics in lung biology.
AB - The epithelial surface of the airways is the largest barrier-forming interface
between the human body and the outside world. It is now well recognized that, at
this strategic position, airway epithelial cells play an eminent role in host
defense by recognizing and responding to microbial exposure. Conversely, inhaled
microorganisms also respond to contact with epithelial cells. Our understanding
of this cross talk is limited, requiring sophisticated experimental approaches to
analyze these complex interactions. High-throughput technologies, such as DNA
microarray analysis and serial analysis of gene expression (SAGE), have been
developed to screen for gene expression levels at large scale within single
experiments. Since their introduction, these hypothesis-generating technologies
have been widely used in diverse areas such as oncology and brain research.
Successful application of these genomics-based technologies has also revealed
novel insights in host-pathogen interactions in both the host and pathogen. This
review aims to provide an overview of the SAGE and microarray technology
illustrated by their application in the analysis of host-pathogen interactions.
In particular, the interactions between epithelial cells in the human lungs and
clinically relevant microorganisms are the central focus of this review.
PMID- 17041014
TI - The reverse mode of the Na(+)/Ca(2+) exchanger provides a source of Ca(2+) for
store refilling following agonist-induced Ca(2+) mobilization.
AB - Agonist-induced contraction of airway smooth muscle (ASM) can be triggered by an
elevation in the intracellular Ca(2+) concentration, primarily through the
release of Ca(2+) from the sarcoplasmic reticulum (SR). The refilling of the SR
is integral for subsequent contractions. It has been suggested that Ca(2+) entry
via store-operated cation (SOC) and receptor-operated cation channels may
facilitate refilling of the SR. Indeed, depletion of the SR activates substantial
inward SOC currents in ASM that are composed of both Ca(2+) and Na(+).
Accumulation of Na(+) within the cell may regulate Ca(2+) handling in ASM by
forcing the Na(+)/Ca(2+) exchanger (NCX) into the reverse mode, leading to the
influx of Ca(2+) from the extracellular domain. Since depletion of the SR
activates substantial inward Na(+) current, it is conceivable that the reverse
mode of the NCX may contribute to the intracellular Ca(2+) pool from which the SR
is refilled. Indeed, successive contractions of bovine ASM, evoked by various
agonists (ACh, histamine, 5-HT, caffeine) were significantly reduced upon removal
of extracellular Na(+); whereas contractions evoked by KCl were unchanged by
Na(+) depletion. Ouabain, a selective inhibitor of the Na(+)/K(+) pump, had no
effect on the reductions observed under normal and zero-Na(+) conditions. KB
R7943, a selective inhibitor of the reverse mode of the NCX, significantly
reduced successive contractions induced by all agonists without altering KCl
responses. Furthermore, KB-R7943 abolished successive caffeine-induced Ca(2+)
transients in single ASM cells. Together, these data suggest a role for the
reverse mode of the NCX in refilling the SR in ASM following Ca(2+) mobilization.
PMID- 17041015
TI - Hydraulic conductance of lung endothelial phenotypes and Starling safety factors
against edema.
AB - Recent permeability studies comparing endothelial cell phenotypes derived from
alveolar and extra-alveolar vessels have significant implications for
interpreting the mechanisms of fluid homeostasis in the intact lung. These
studies indicate that confluent monolayers of rat pulmonary microvascular
endothelial cells had a hydraulic conductance (L(p)) that was only 5% and a
transendothelial flux rate for 72-kDa dextran only 9% of values determined for
rat pulmonary artery endothelial cell monolayers. On the basis of previous
studies partitioning the filtration coefficients between alveolar and extra
alveolar vascular segments in rat lungs and previous studies of lymph albumin
fluxes and permeability, the contribution of the alveolar capillary segment to
total albumin flux in lymph was estimated to be less than 10%. In addition, the
Starling safety factors against the edema calculated for the alveolar capillaries
are quite different from those estimated for whole lung. Estimates of the edema
safety factor due to increased filtration across the alveolar capillary wall
based on the low L(p) indicate it is quantitatively the greatest safety factor,
although it would be a minor safety factor for extra-alveolar vessels. Also, a
markedly higher effective protein osmotic absorptive force for plasma proteins
must occur in the capillaries relative to extra-alveolar vessels. The lower L(p)
for alveolar capillaries also has implications for the sequence of hydrostatic
edema formation, and it also may have a role in preventing exercise-induced
alveolar flooding.
PMID- 17041016
TI - Self-perceived weight status and exercise adequacy.
AB - The growing prevalence of obesity and inadequate physical activity levels in the
population highlight an opportunity to examine public opinion about exercise, as
well as the perceived adequacy of exercise among adults. This article summarizes
findings from a 2004 survey of exercise habits and beliefs among Michigan adults
using bivariate and logit analysis. It examines perceptions of weight status and
adequacy of exercise, illuminates public opinion regarding the importance and
value of exercise as one aspect of active living and highlights some of the
perceived barriers and facilitators to exercise. The results indicate that people
believe that they exercise enough, but that demographic, socio-economic and
attitudinal factors may be potential barriers to physical activity. It is
important to establish and/or bolster individual and community support structures
while also minimizing potential barriers to exercise at the individual,
organizational and community levels.
PMID- 17041017
TI - Use of research by the Australian health promotion workforce.
AB - This paper examines the attitudes and practices of Australian health promotion
practitioners toward evidence-based practice (EBP). The study used a survey
methodology and questionnaires were sent to 1114 members of the Australian Health
Promotion Association. A response rate of 27% (n = 277) was achieved. The data
showed that the vast majority of participant's attitudes toward EBP was very
welcoming. However, in practice the impact of EBP was limited. Participants
identified a range of significant barriers to implementing EBP including
organizational culture, policy directives and lack of resources. A range of
concerns was also identified regarding the applicability of the medically based
EBP model within health promotion, which is based upon a social model of health.
The findings highlight the importance of acknowledging the complexity of health
promotion interventions and working toward developing an appropriate evidence
base.
PMID- 17041018
TI - Comparing stage of change and behavioral intention to understand fruit intake.
AB - We explored if the pre-action Transtheoretical stages of change are indeed
discrete stages for fruit intakes. In a longitudinal design, a cohort of 735
adults completed electronic questionnaires assessing fruit intake, stages of
change and intention to increase fruit intake at baseline and 35 and 67 days
follow-up. A dichotomization of a continuous intention measure ('pseudostages')
was compared with precontemplation and contemplation stages. The results showed
(i) that pseudostages and stages of change were strongly associated; (ii) that
for most respondents, stability and transitions in stages of change resembled
transitions in pseudostage, while test-retest reliabilities for both measures
were similar and (iii) that pseudostages and the continuous intention measure
were stronger predictors of fruit intake than stage of change. We conclude that
pre-action stages of change for fruit are not different from a mere
categorization of a continuous intention measure.
PMID- 17041019
TI - Nutrition knowledge and body mass index.
AB - The purpose of this study was to investigate the relationship between nutrition
knowledge and body mass index (BMI). The General Nutrition Questionnaire was
distributed to 500 individuals on the database of a large general practice.
Results demonstrated that there was no significant correlation between levels of
nutrition knowledge and BMI; however, a high level of nutrition knowledge was
found among the sample. This suggests that a knowledge deficit may not be the
most significant factor preventing overweight individuals from adopting a
healthier diet and questions the utility of purely educational approaches to
dietary behaviour change. Evidence-based health behaviour change techniques are
discussed.
PMID- 17041020
TI - Young people and physical activity: a systematic review matching their views to
effective interventions.
AB - A systematic review was conducted to examine the barriers to, and facilitators
of, physical activity among young people (11-16 years). The review focused on the
wider determinants of health, examining community- and society-level
interventions. Four trials and 16 studies of young people's views were included.
Evidence for the effectiveness of the interventions was limited, with some
suggestions of improvements in knowledge and possible differences according to
gender. Young women in particular identified barriers to physical activity
associated with certain ways of providing physical education in schools. Young
people in general identified a need for increased choice and facilities within
the community and emphasized physical activity's social side. Some of the
barriers and facilitators identified by young people had been addressed by
'soundly evaluated' effective interventions but significant gaps were identified
where no evaluated interventions appear to have been published (e.g. initiatives
explicitly addressing gender issues or the combination of sport and other leisure
activities), or where there were no soundly evaluated interventions. Rigorous
evaluation is required particularly to assess initiatives that address the
limited practical and material resources that young people identify as barriers
to physical activity.
PMID- 17041021
TI - Infant-feeding attitudes of expectant mothers in Northern Ireland.
AB - Northern Ireland (NI) has one of the lowest rates of breast-feeding initiation
and duration in both the UK and the industrialized world. This study therefore
aimed to explore the relationship between infant-feeding attitudes and feeding
intention and outcome in expectant mothers within NI. Expectant mothers (n = 200)
were recruited from hospital antenatal booking clinics. Each completed a
demographic questionnaire and the self-administered Iowa Infant Feeding Attitude
Scale (IIFAS). Participants (n = 192) were followed up after birth through the
Northern Ireland Maternity System. The IIFAS distinguished between those mothers
who intended to breast-feed (higher IIFAS scores) and those who intended to
artificially feed (lower IIFAS scores) as well as between those who breast-fed
and those who artificially fed on discharge from hospital. The IIFAS was also
able to distinguish between mothers in regard to feeding intention and outcome on
the basis of education, socio-economic class, income and marital status. This
suggests that the IIFAS could prove useful in the targeting and evaluation of
intervention to promote breast-feeding.
PMID- 17041022
TI - Cultural accommodation of the Strengthening Families Programme 10-14: UK Phase I
study.
AB - Social and cultural differences between the United States and the United Kingdom
mean that positive results from US prevention programmes may not translate to the
United Kingdom. The Strengthening Families Programme 10-14 (SFP10-14) has been
evaluated in a large Phase III randomized controlled trial in rural Iowa in the
United States and shown to be effective for delaying alcohol and drug initiation.
This paper reports the first stage of the adaptation and evaluation of the SFP10
14 for the United Kingdom through a process of cultural accommodation of the
SFP10-14 materials and format. Themes that emerged in nominal group and focus
group research with young people and their parents indicated that changes to the
US SFP10-14 materials needed to consider language, narrators, realism,
acceptability of exercises/games, perceived religiosity and ethnic
representativeness. However, not all changes reflected straightforward cultural
differences, as adaptations were also required to improve the quality and to
update the material, indicating that cultural accommodation does not necessarily
imply cultural diversity.
PMID- 17041023
TI - Dynamic response of prevacuolar compartments to brefeldin a in plant cells.
AB - Little is known about the dynamics and molecular components of plant prevacuolar
compartments (PVCs) in the secretory pathway. Using transgenic tobacco (Nicotiana
tabacum) Bright-Yellow-2 (BY-2) cells expressing membrane-anchored yellow
fluorescent protein (YFP) reporters marking Golgi or PVCs, we have recently
demonstrated that PVCs are mobile multivesicular bodies defined by vacuolar
sorting receptor proteins. Here, we demonstrate that Golgi and PVCs have
different sensitivity in response to brefeldin A (BFA) treatment in living
tobacco BY-2 cells. BFA at low concentrations (5-10 microg mL(-1)) induced YFP
marked Golgi stacks to form both endoplasmic reticulum-Golgi hybrid structures
and BFA-induced aggregates, but had little effect on YFP-marked PVCs in
transgenic BY-2 cells at both confocal and immunogold electron microscopy levels.
However, BFA at high concentrations (50-100 microg mL(-1)) caused both YFP-marked
Golgi stacks and PVCs to form aggregates in a dose- and time-dependent manner.
Normal Golgi or PVC signals can be recovered upon removal of BFA from the culture
media. Confocal immunofluorescence and immunogold electron microscopy studies
with specific organelle markers further demonstrate that the PVC aggregates are
distinct, but physically associated, with Golgi aggregates in BFA-treated cells
and that PVCs might lose their internal vesicle structures at high BFA
concentration. In addition, vacuolar sorting receptor-marked PVCs in root-tip
cells of tobacco, pea (Pisum sativum), mung bean (Vigna radiata), and Arabidopsis
(Arabidopsis thaliana) upon BFA treatment are also induced to form similar
aggregates. Thus, we have demonstrated that the effects of BFA are not limited to
endoplasmic reticulum and Golgi, but extend to PVC in the endomembrane system,
which might provide a quick tool for distinguishing Golgi from PVC for its
identification and characterization, as well as a possible new tool in studying
PVC-mediated protein traffic in plant cells.
PMID- 17041024
TI - Common plantain. A collection of expressed sequence tags from vascular tissue and
a simple and efficient transformation method.
AB - The vascular tissue of higher plants consists of specialized cells that differ
from all other cells with respect to their shape and size, their organellar
composition, their extracellular matrix, the type of their plasmodesmata, and
their physiological functions. Intact and pure vascular tissue can be isolated
easily and rapidly from leaf blades of common plantain (Plantago major), a plant
that has been used repeatedly for molecular studies of phloem transport. Here, we
present a transcriptome analysis based on 5,900 expressed sequence tags (ESTs)
and 3,247 independent mRNAs from the Plantago vasculature. The vascular
specificity of these ESTs was confirmed by the identification of well-known
phloem or xylem marker genes. Moreover, reverse transcription-polymerase chain
reaction, macroarray, and northern analyses revealed genes and metabolic pathways
that had previously not been described to be vascular specific. Moreover, common
plantain transformation was established and used to confirm the vascular
specificity of a Plantago promoter-beta-glucuronidase construct in transgenic
Plantago plants. Eventually, the applicability and usefulness of the obtained
data were also demonstrated for other plant species. Reporter gene constructs
generated with promoters from Arabidopsis (Arabidopsis thaliana) homologs of
newly identified Plantago vascular ESTs revealed vascular specificity of these
genes in Arabidopsis as well. The presented vascular ESTs and the newly developed
transformation system represent an important tool for future studies of
functional genomics in the common plantain vasculature.
PMID- 17041025
TI - SIZ1 small ubiquitin-like modifier E3 ligase facilitates basal thermotolerance in
Arabidopsis independent of salicylic acid.
AB - Small ubiquitin-like modifier (SUMO) conjugation/deconjugation to heat shock
transcription factors regulates DNA binding of the peptides and activation of
heat shock protein gene expression that modulates thermal adaptation in
metazoans. SIZ1 is a SUMO E3 ligase that facilitates SUMO conjugation to
substrate target proteins (sumoylation) in Arabidopsis (Arabidopsis thaliana).
siz1 T-DNA insertional mutations (siz1-2 and siz1-3; Miura et al., 2005) cause
basal, but not acquired, thermosensitivity that occurs in conjunction with
hyperaccumulation of salicylic acid (SA). NahG encodes a salicylate hydroxylase,
and expression in siz1-2 seedlings reduces endogenous SA accumulation to that of
wild-type levels and further increases thermosensitivity. High temperature
induces SUMO1/2 conjugation to peptides in wild type but to a substantially
lesser degree in siz1 mutants. However, heat shock-induced expression of genes,
including heat shock proteins, ascorbate peroxidase 1 and 2, is similar in siz1
and wild-type seedlings. Together, these results indicate that SIZ1 and, by
inference, sumoylation facilitate basal thermotolerance through processes that
are SA independent.
PMID- 17041026
TI - A eukaryotic factor required for accumulation of the chloroplast NAD(P)H
dehydrogenase complex in Arabidopsis.
AB - The NAD(P)H dehydrogenase (NDH) complex in chloroplasts mediates photosystem I
cyclic and chlororespiratory electron transport. Eleven chloroplast genes and
three nuclear genes have been identified as encoding Ndh subunits, but the entire
subunit composition is still unknown. An Arabidopsis (Arabidopsis thaliana)
chlororespiratory reduction (crr3) mutant was isolated based on its lack of
transient increase in chlorophyll fluorescence after actinic light illumination;
this was due to a specific defect in accumulation of the NDH complex. The CRR3
gene (At2g01590) encodes a novel protein containing a putative plastid-targeting
signal and a transmembrane domain. Consistent with the gene structure, CRR3
localized to the membrane fraction of chloroplasts. In addition to the essential
function of CRR3 in stabilizing the NDH complex, the NDH complex is also required
for the accumulation of CRR3. These results suggest that CRR3 interacts with the
NDH complex in the thylakoid membrane. In contrast to other subunits in the
chloroplast NDH complex, CRR3 is not conserved in cyanobacteria from which the
chloroplast NDH complex is believed to have originated. We propose that CRR3 is a
subunit of the NDH complex, which is specific to the chloroplast.
PMID- 17041027
TI - Geminivirus infection up-regulates the expression of two Arabidopsis protein
kinases related to yeast SNF1- and mammalian AMPK-activating kinases.
AB - Geminivirus Rep-interacting kinase 1 (GRIK1) and GRIK2 constitute a small protein
kinase family in Arabidopsis (Arabidopsis thaliana). An earlier study showed that
a truncated version of GRIK1 binds to the geminivirus replication protein AL1. We
show here both full-length GRIK1 and GRIK2 interact with AL1 in yeast two-hybrid
studies. Using specific antibodies, we showed that both Arabidopsis kinases are
elevated in infected leaves. Immunoblot analysis of healthy plants revealed that
GRIK1 and GRIK2 are highest in young leaf and floral tissues and low or
undetectable in mature tissues. Immunohistochemical staining showed that the
kinases accumulate in the shoot apical meristem, leaf primordium, and emerging
petiole. Unlike the protein patterns, GRIK1 and GRIK2 transcript levels only show
a small increase during infection and do not change significantly during
development. Treating healthy seedlings and infected leaves with the proteasome
inhibitor MG132 resulted in higher GRIK1 and GRIK2 protein levels, whereas
treatment with the translation inhibitor cycloheximide reduced both kinases,
demonstrating that their accumulation is modulated by posttranscriptional
processes. Phylogenetic comparisons indicated that GRIK1, GRIK2, and related
kinases from Medicago truncatula and rice (Oryza sativa) are most similar to the
yeast kinases PAK1, TOS3, and ELM1 and the mammalian kinase CaMKK, which activate
the yeast kinase SNF1 and its mammalian homolog AMPK, respectively.
Complementation studies using a PAK1/TOS3/ELM1 triple mutant showed that GRIK1
and GRIK2 can functionally replace the yeast kinases, suggesting that the
Arabidopsis kinases mediate one or more processes during early plant development
and geminivirus infection by activating SNF1-related kinases.
PMID- 17041028
TI - Developmentally controlled farnesylation modulates AtNAP1;1 function in cell
proliferation and cell expansion during Arabidopsis leaf development.
AB - In multicellular organisms, organogenesis requires tight control and coordination
of cell proliferation, cell expansion, and cell differentiation. We have
identified Arabidopsis (Arabidopsis thaliana) nucleosome assembly protein 1
(AtNAP1;1) as a component of a regulatory mechanism that connects cell
proliferation to cell growth and expansion during Arabidopsis leaf development.
Molecular, biochemical, and kinetic studies of AtNAP1;1 gain- or loss-of-function
mutants indicate that AtNAP1;1 promotes cell proliferation or cell expansion in a
developmental context and as a function of the farnesylation status of the
protein. AtNAP1;1 was farnesylated and localized to the nucleus during the cell
proliferation phase of leaf development when it promotes cell division. Later in
leaf development, nonfarnesylated AtNAP1;1 accumulates in the cytoplasm when it
promotes cell expansion. Ectopic expression of nonfarnesylated AtNAP1;1, which
localized to the cytoplasm, disrupts this developmental program by promoting
unscheduled cell expansion during the proliferation phase.
PMID- 17041030
TI - NAD(P)H oscillates in pollen tubes and is correlated with tip growth.
AB - The location and changes in NAD(P)H have been monitored during oscillatory growth
in pollen tubes of lily (Lilium formosanum) using the endogenous fluorescence of
the reduced coenzyme (excitation, 360 nm; emission, >400 nm). The strongest
signal resides 20 to 40 microm behind the apex where mitochondria (stained with
Mitotracker Green) accumulate. Measurements at 3-s intervals reveal that NAD(P)H
dependent fluorescence oscillates during oscillatory growth. Cross-correlation
analysis indicates that the peaks follow growth maxima by 7 to 11 s or 77 degrees
to 116 degrees, whereas the troughs anticipate growth maxima by 5 to 10 s or 54
degrees to 107 degrees. We have focused on the troughs because they anticipate
growth and are as strongly correlated with growth as the peaks. Analysis of the
signal in 10-microm increments along the length of the tube indicates that the
troughs are most advanced in the extreme apex. However, this signal moves
basipetally as a wave, being in phase with growth rate oscillations at 50 to 60
microm from the apex. We suggest that the changes in fluorescence are due to an
oscillation between the reduced (peaks) and oxidized (troughs) states of the
coenzyme and that an increase in the oxidized state [NAD(P)(+)] may be coupled to
the synthesis of ATP. We also show that diphenyleneiodonium, an inhibitor of
NAD(P)H dehydrogenases, causes an increase in fluorescence and a decrease in tube
growth. Finally, staining with 5-(and-6)-chloromethyl-2',7'
dichlorohydrofluorescein acetate indicates that reactive oxygen species are most
abundant in the region where mitochondria accumulate and where NAD(P)H
fluorescence is maximal.
PMID- 17041029
TI - Heterologous expression and molecular and cellular characterization of CaPUB1
encoding a hot pepper U-Box E3 ubiquitin ligase homolog.
AB - The U-box motif is a conserved domain found in the diverse isoforms of E3
ubiquitin ligase in eukaryotes. From water-stressed hot pepper (Capsicum annuum
L. cv Pukang) plants, we isolated C. annuum putative U-box protein 1 (CaPUB1),
which encodes a protein containing a single U-box motif in its N-terminal region.
In vitro ubiquitination and site-directed mutagenesis assays revealed that CaPUB1
possessed E3 ubiquitin ligase activity and that the U-box motif was indeed
essential for its enzyme activity. RNA gel-blot analysis showed that CaPUB1 mRNA
was induced rapidly by a broad spectrum of abiotic stresses, including drought,
high salinity, cold temperature, and mechanical wounding, but not in response to
ethylene, abscisic acid, or a bacterial pathogen, suggesting its role in the
early events in the abiotic-related defense response. Because transgenic work was
extremely difficult in hot pepper, in this study we overexpressed CaPUB1 in
Arabidopsis (Arabidopsis thaliana) to provide cellular information on the
function of this gene in the development and plant responses to abiotic stresses.
Transgenic Arabidopsis plants that constitutively expressed the CaPUB1 gene under
the control of the cauliflower mosaic virus 35S promoter had markedly longer
hypocotyls and roots and grew more rapidly than the wild type, leading to an
early bolting phenotype. Microscopic analysis showed that 35S::CaPUB1 roots had
increased numbers of small-sized cells, resulting in disordered, highly populated
cell layers in the cortex, endodermis, and stele. In addition, CaPUB1
overexpressing plants displayed increased sensitivity to water stress and mild
salinity. These results indicate that CaPUB1 is functional in Arabidopsis cells,
thereby effectively altering cell and tissue growth and also the response to
abiotic stresses. Comparative proteomic analysis showed that the level of RPN6
protein, a non-ATPase subunit of the 26S proteasome complex, was significantly
reduced in 35SCaPUB1 seedlings as compared to the wild type. Pull-down and
ubiquitination assays demonstrated that RPN6 interacted physically with CaPUB1
and was ubiquitinated in a CaPUB1-dependent manner in vitro. Although the
physiological function of CaPUB1 is not yet clear, there are several
possibilities for its involvement in a subset of physiological responses to
counteract dehydration and high-salinity stresses in transgenic Arabidopsis
seedlings.
PMID- 17041031
TI - Interactions between MUR10/CesA7-dependent secondary cellulose biosynthesis and
primary cell wall structure.
AB - Primary cell walls are deposited and remodeled during cell division and
expansion. Secondary cell walls are deposited in specialized cells after the
expansion phase. It is presently unknown whether and how these processes are
interrelated. The Arabidopsis (Arabidopsis thaliana) MUR10 gene is required for
normal primary cell wall carbohydrate composition in mature leaves as well as for
normal plant growth, hypocotyl strength, and fertility. The overall sugar
composition of young mur10 seedlings is not significantly altered; however, the
relative proportion of pectin side chains is shifted toward an increase in 1 -->
5-alpha-arabinan relative to 1 --> 4-beta-galactan. mur10 seedlings display
reduced fucogalactosylation of tightly cell wall-bound xyloglucan. Expression
levels of genes encoding either nucleotide sugar interconversion enzymes or
glycosyl transferases, known to be involved in primary and secondary cell wall
biosynthesis, are generally unaffected; however, the CesA7 transcript is
specifically suppressed in the mur10-1 allele. The MUR10 locus is identical with
the CesA7 gene, which encodes a cellulose catalytic subunit previously thought to
be specifically involved in secondary cell wall formation. The xylem vessels in
young mur10 hypocotyls are collapsed and their birefringence is lost. Moreover, a
fucogalactosylated xyloglucan epitope is reduced and a 1 --> 5-alpha-arabinan
epitope increased in every cell type in mur10 hypocotyls, including cells that do
not deposit secondary walls. mur10 also displays altered distribution of an
arabinogalactan-protein epitope previously associated with xylem differentiation
and secondary wall thickening. This work indicates the existence of a mechanism
that senses secondary cell wall integrity and controls biosynthesis or structural
remodeling of primary cell walls and cellular differentiation.
PMID- 17041032
TI - The liverwort Marchantia polymorpha expresses orthologs of the fungal Agaricus
bisporus agglutinin family.
AB - A lectin different from the previously described mannose-binding agglutinins has
been isolated from the liverwort Marchantia polymorpha. Biochemical
characterization of the purified lectin combined with the data from earlier
transcriptome analyses demonstrated that the novel M. polymorpha agglutinin is
not related to any of the known plant lectin families, but closely resembles the
Agaricus bisporus-type lectins, which hitherto have been found exclusively in
fungi. Immunolocalization studies confirmed that lectin is exclusively associated
with plant cells, ruling out the possibility of a fungal origin. Extensive
screening of publicly accessible databases confirmed that, apart from fungi, the
occurrence of A. bisporus-type lectins is confined to M. polymorpha and the moss
Tortula ruralis. Expression of a typical fungal protein in a liverwort and a moss
raises the question of the origin of the corresponding genes. Regardless of the
evolutionary origin, the presence of a functional A. bisporus lectin ortholog in
M. polymorpha provides evidence for the expression of an additional carbohydrate
binding domain in Viridiplantae.
PMID- 17041033
TI - Embolism formation during freezing in the wood of Picea abies.
AB - Freeze-thaw events can cause embolism in plant xylem. According to classical
theory, gas bubbles are formed during freezing and expand during thawing.
Conifers have proved to be very resistant to freeze-thaw induced embolism,
because bubbles in tracheids are small and redissolve during thawing. In
contrast, increasing embolism rates upon consecutive freeze-thaw events were
observed that cannot be explained by the classical mechanism. In this study,
embolism formation during freeze-thaw events was analyzed via ultrasonic and Cryo
scanning electron microscope techniques. Twigs of Picea abies L. Karst. were
subjected to up to 120 freeze-thaw cycles during which ultrasonic acoustic
emissions, xylem temperature, and diameter variations were registered. In
addition, the extent and cross-sectional pattern of embolism were analyzed with
staining experiments and Cryo-scanning electron microscope observations. Embolism
increased with the number of freeze-thaw events in twigs previously dehydrated to
a water potential of -2.8 MPa. In these twigs, acoustic emissions were
registered, while saturated twigs showed low, and totally dehydrated twigs showed
no, acoustic activity. Acoustic emissions were detected only during the freezing
process. This means that embolism was formed during freezing, which is in
contradiction to the classical theory of freeze-thaw induced embolism. The
clustered pattern of embolized tracheids in cross sections indicates that air
spread from a dysfunctional tracheid to adjacent functional ones. We hypothesize
that the low water potential of the growing ice front led to a decrease of the
potential in nearby tracheids. This may result in freezing-induced air seeding.
PMID- 17041034
TI - Nuclear magnetic resonance spectroscopy-based metabolite profiling of transgenic
tomato fruit engineered to accumulate spermidine and spermine reveals enhanced
anabolic and nitrogen-carbon interactions.
AB - Polyamines are ubiquitous aliphatic amines that have been implicated in myriad
processes, but their precise biochemical roles are not fully understood. We have
carried out metabolite profiling analyses of transgenic tomato (Solanum
lycopersicum) fruit engineered to accumulate the higher polyamines spermidine
(Spd) and spermine (Spm) to bring an insight into the metabolic processes that
Spd/Spm regulate in plants. NMR spectroscopic analysis revealed distinct
metabolite trends in the transgenic and wild-type/azygous fruits ripened off the
vine. Distinct metabolites (glutamine, asparagine, choline, citrate, fumarate,
malate, and an unidentified compound A) accumulated in the red transgenic fruit,
while the levels of valine, aspartic acid, sucrose, and glucose were
significantly lower as compared to the control (wild-type and azygous) red fruit.
The levels of isoleucine, glucose, gamma-aminobutyrate, phenylalanine, and
fructose remained similar in the nontransgenic and transgenic fruits. Statistical
treatment of the metabolite variables distinguished the control fruits from the
transgenic fruit and provided credence to the pronounced, differential metabolite
profiles seen during ripening of the transgenic fruits. The pathways involved in
the nitrogen sensing/signaling and carbon metabolism seem preferentially
activated in the high Spd/Spm transgenics. The metabolite profiling analysis
suggests that Spd and Spm are perceived as nitrogenous metabolites by the fruit
cells, which in turn results in the stimulation of carbon sequestration. This is
seen manifested in higher respiratory activity and up-regulation of
phosphoenolpyruvate carboxylase and NADP-dependent isocitrate dehydrogenase
transcripts in the transgenic fruit compared to controls, indicating high
metabolic status of the transgenics even late in fruit ripening.
PMID- 17041035
TI - Analysis of proline reduction in the nosocomial pathogen Clostridium difficile.
AB - Clostridium difficile, a proteolytic strict anaerobe, has emerged as a clinically
significant nosocomial pathogen in recent years. Pathogenesis is due to the
production of lethal toxins, A and B, members of the large clostridial cytotoxin
family. Although it has been established that alterations in the amino acid
content of the growth medium affect toxin production, the molecular mechanism for
this observed effect is not yet known. Since there is a paucity of information on
the amino acid fermentation pathways used by this pathogen, we investigated
whether Stickland reactions might be at the heart of its bioenergetic pathways.
Growth of C. difficile on Stickland pairs yielded large increases in cell density
in a limiting basal medium, demonstrating that these reactions are tied to ATP
production. Selenium supplementation was required for this increase in cell
yield. Analysis of genome sequence data reveals genes encoding the protein
components of two key selenoenzyme reductases, glycine reductase and d-proline
reductase (PR). These selenoenzymes were expressed upon the addition of the
corresponding Stickland acceptor (glycine, proline, or hydroxyproline).
Purification of the selenoenzyme d-proline reductase revealed a mixed complex of
PrdA and PrdB (SeCys-containing) proteins. PR utilized only d-proline but not l
hydroxyproline, even in the presence of an expressed and purified proline
racemase. PR was found to be independent of divalent cations, and zinc was a
potent inhibitor of PR. These results show that Stickland reactions are key to
the growth of C. difficile and that the mechanism of PR may differ significantly
from that of previously studied PR from nonpathogenic species.
PMID- 17041036
TI - Role of RelGsu in stress response and Fe(III) reduction in Geobacter
sulfurreducens.
AB - Geobacter species are key members of the microbial community in many subsurface
environments in which dissimilatory metal reduction is an important process. The
genome of Geobacter sulfurreducens contains a gene designated rel(Gsu), which
encodes a RelA homolog predicted to catalyze both the synthesis and the
degradation of guanosine 3',5'-bispyrophosphate (ppGpp), a regulatory molecule
that signals slow growth in response to nutrient limitation in bacteria. To
evaluate the physiological role of Rel(Gsu) in G. sulfurreducens, a rel(Gsu)
mutant was constructed and characterized, and ppGpp levels were monitored under
various conditions in both the wild-type and rel(Gsu) mutant strains. In the wild
type strain, ppGpp and ppGp were produced in response to acetate and nitrogen
deprivation, whereas exposure to oxygen resulted in an accumulation of ppGpp
alone. Neither ppGpp nor ppGp could be detected in the rel(Gsu) mutant. The
rel(Gsu) mutant consistently grew to a higher cell density than the wild type in
acetate-fumarate medium and was less tolerant of oxidative stress than the wild
type. The capacity for Fe(III) reduction was substantially diminished in the
mutant. Microarray and quantitative reverse transcription-PCR analyses indicated
that during stationary-phase growth, protein synthesis genes were up-regulated in
the rel(Gsu) mutant and genes involved in stress responses and electron
transport, including several implicated in Fe(III) reduction, were down-regulated
in the mutant. The results are consistent with a role for Rel(Gsu) in regulating
growth, stress responses, and Fe(III) reduction in G. sulfurreducens under
conditions likely to be prevalent in subsurface environments.
PMID- 17041037
TI - Genome sequence of Avery's virulent serotype 2 strain D39 of Streptococcus
pneumoniae and comparison with that of unencapsulated laboratory strain R6.
AB - Streptococcus pneumoniae (pneumococcus) is a leading human respiratory pathogen
that causes a variety of serious mucosal and invasive diseases. D39 is an
historically important serotype 2 strain that was used in experiments by Avery
and coworkers to demonstrate that DNA is the genetic material. Although isolated
nearly a century ago, D39 remains extremely virulent in murine infection models
and is perhaps the strain used most frequently in current studies of pneumococcal
pathogenesis. To date, the complete genome sequences have been reported for only
two S. pneumoniae strains: TIGR4, a recent serotype 4 clinical isolate, and
laboratory strain R6, an avirulent, unencapsulated derivative of strain D39. We
report here the genome sequences and new annotation of two different isolates of
strain D39 and the corrected sequence of strain R6. Comparisons of these three
related sequences allowed deduction of the likely sequence of the D39 progenitor
and mutations that arose in each isolate. Despite its numerous repeated sequences
and IS elements, the serotype 2 genome has remained remarkably stable during
cultivation, and one of the D39 isolates contains only five relatively minor
mutations compared to the deduced D39 progenitor. In contrast, laboratory strain
R6 contains 71 single-base-pair changes, six deletions, and four insertions and
has lost the cryptic pDP1 plasmid compared to the D39 progenitor strain. Many of
these mutations are in or affect the expression of genes that play important
roles in regulation, metabolism, and virulence. The nature of the mutations that
arose spontaneously in these three strains, the relative global transcription
patterns determined by microarray analyses, and the implications of the D39
genome sequences to studies of pneumococcal physiology and pathogenesis are
presented and discussed.
PMID- 17041038
TI - Characterization of the Moraxella catarrhalis opa-like protein, OlpA, reveals a
phylogenetically conserved family of outer membrane proteins.
AB - Moraxella catarrhalis is a human-restricted pathogen that can cause respiratory
tract infections. In this study, we identified a previously uncharacterized 24
kDa outer membrane protein with a high degree of similarity to Neisseria Opa
protein adhesins, with a predicted beta-barrel structure consisting of eight
antiparallel beta-sheets with four surface-exposed loops. In striking contrast to
the antigenically variable Opa proteins, the M. catarrhalis Opa-like protein
(OlpA) is highly conserved and constitutively expressed, with 25 of 27 strains
corresponding to a single variant. Protease treatment of intact bacteria and
isolation of outer membrane vesicles confirm that the protein is surface exposed
yet does not bind host cellular receptors recognized by neisserial Opa proteins.
Genome-based analyses indicate that OlpA and Opa derive from a conserved family
of proteins shared by a broad array of gram-negative bacteria.
PMID- 17041039
TI - Kinase activity of overexpressed HipA is required for growth arrest and multidrug
tolerance in Escherichia coli.
AB - Overexpression of the HipA protein of the HipBA toxin/antitoxin module leads to
multidrug tolerance in Escherichia coli. HipA is a "toxin" that causes reversible
dormancy, whereas HipB is an antitoxin that binds HipA and acts as a
transcriptional repressor of the hipBA operon. Comparative sequence analysis
shows that HipA is a member of the phosphatidylinositol 3/4-kinase superfamily.
The kinase activity of HipA was examined. HipA was autophosphorylated in the
presence of ATP in vitro, and the purified protein appeared to carry a single
phosphate group on serine 150. Thus, HipA is a serine kinase that is at least
partially phosphorylated in vivo. Overexpression of HipA caused inhibition of
cell growth and increase in persister formation. Replacing conserved aspartate
309 in the conserved kinase active site or aspartate 332 in the Mg2+-binding site
with glutamine produced mutant proteins that lost the ability to stop cellular
growth upon overexpression. Replacing serine 150 with alanine yielded a similarly
inactive protein. The mutant proteins were then examined for their ability to
increase antibiotic tolerance. Cells overexpressing wild-type HipA were highly
tolerant to cefotaxime, a cell wall synthesis inhibitor, to ofloxacin, a
fluoroquinolone inhibitor of DNA gyrase, and to topoisomerase IV and were almost
completely resistant to killing by mitomycin C, which forms DNA adducts. The
mutant proteins did not protect cells from cefotaxime or ofloxacin and had an
impaired ability to protect from mitomycin C. Taken together, these results
suggest that the protein kinase activity of HipA is essential for persister
formation.
PMID- 17041040
TI - Analysis of the roles of FlgP and FlgQ in flagellar motility of Campylobacter
jejuni.
AB - Flagellar motility is an important determinant of Campylobacter jejuni that is
required for promoting interactions with various hosts to promote gastroenteritis
in humans or commensal colonization of many animals. In a previous study, we
identified a nonmotile mutant of C. jejuni 81-176 with a transposon insertion in
Cj1026c, but verification of the role of the encoded protein in motility was not
determined. In this study, we have determined that Cj1026c and the gene
immediately downstream, Cj1025c (here annotated as flgP and flgQ, respectively),
are both required for motility of C. jejuni but not for flagellar biosynthesis.
FlgP and FlgQ are not components of the transcriptional regulatory cascades to
activate sigma(28)- or sigma(54)-dependent expression of flagellar genes. In
addition, expression of flgP and flgQ is not largely dependent on sigma(28) or
sigma(54). Immunblot analyses revealed that the majority of FlgP in C. jejuni is
associated with the outer membrane. However, in the absence of FlgQ, the amounts
of FlgP in the outer membrane of C. jejuni are greatly reduced, suggesting that
FlgQ may be required for localization or stability of FlgP at this location. This
study provides insight into features of FlgP and FlgQ, two proteins with
previously undefined functions that are required for the larger, multicomponent
flagellar system of C. jejuni that is necessary for motility.
PMID- 17041041
TI - Agrobacterium tumefaciens soxR is involved in superoxide stress protection and
also directly regulates superoxide-inducible expression of itself and a target
gene.
AB - Inactivation of Agrobacterium tumefaciens soxR increases sensitivity to
superoxide generators. soxR expression is highly induced by superoxide stress and
is autoregulated. SoxR also directly regulates the superoxide-inducible
expression of atu5152. Taken together, the physiological role of soxR and the
mechanism by which it regulates expression of target genes make the A.
tumefaciens SoxR system different from other bacterial systems.
PMID- 17041042
TI - Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron
utilization.
AB - The pathogenesis of human infections caused by the gram-positive microbe
Staphylococcus aureus has been previously shown to be reliant on the acquisition
of iron from host hemoproteins. The iron-regulated surface determinant system
(Isd) encodes a heme transport apparatus containing three cell wall-anchored
proteins (IsdA, IsdB, and IsdH) that are exposed on the staphylococcal surface
and hence have the potential to interact with human hemoproteins. Here we report
that S. aureus can utilize the host hemoproteins hemoglobin and myoglobin, but
not hemopexin, as iron sources for bacterial growth. We demonstrate that
staphylococci capture hemoglobin on the bacterial surface via IsdB and that
inactivation of isdB, but not isdA or isdH, significantly decreases hemoglobin
binding to the staphylococcal cell wall and impairs the ability of S. aureus to
utilize hemoglobin as an iron source. Stable-isotope-tracking experiments
revealed removal of heme iron from hemoglobin and transport of this compound into
staphylococci. Importantly, mutants lacking isdB, but not isdH, display a
reduction in virulence in a murine model of abscess formation. Thus, IsdB
mediated scavenging of iron from hemoglobin represents an important virulence
strategy for S. aureus replication in host tissues and for the establishment of
persistent staphylococcal infections.
PMID- 17041043
TI - Molecular evolution of the H-NS protein: interaction with Hha-like proteins is
restricted to enterobacteriaceae.
AB - We show here that chromosomal hha-like genes are restricted to the
Enterobacteriaceae. The H-NS N-terminal domain of members of this family includes
an unaltered seven-amino-acid sequence located between helixes 1 and 2, termed
the Hha signature, that contains key residues for H-NS-Hha interaction.
PMID- 17041044
TI - Proteolytic processing is not essential for multiple functions of the Escherichia
coli autotransporter adhesin involved in diffuse adherence (AIDA-I).
AB - The Escherichia coli adhesin involved in diffuse adherence (AIDA-I), like many
other autotransporter proteins, is released in the periplasm as a proprotein
undergoing proteolytic processing after its translocation across the outer
membrane. The proprotein is cleaved into a membrane-embedded fragment, AIDAc, and
an extracellular fragment, the mature AIDA-I adhesin. The latter remains
noncovalently associated with the outer membrane and can be released by heat
treatment. The mechanism of cleavage of the proprotein and its role in the
functionality of AIDA-I are not understood. Here, we show that cleavage is
independent of the amount of AIDA-I in the outer membrane, suggesting an
intramolecular autoproteolytic mechanism or a cleavage mediated by an unknown
protease. We show that the two fragments, mature AIDA-I and AIDAc, can be
cosolubilized and copurified in a folded and active conformation. We observed
that the release by heat treatment results from the unfolding of AIDA-I and that
the interaction of AIDA-I with AIDAc seems to be disturbed only by denaturation.
We constructed an uncleavable point mutant of AIDA-I, where a serine of the
cleavage site was changed into a leucine, and showed that adhesion,
autoaggregation, and biofilm formation mediated by the mutant are
indistinguishable from the wild-type levels. Lastly, we show that both proteins
can mediate the invasion of cultured epithelial cells. Taken together, our
experiments suggest that the proteolytic processing of AIDA-I plays a minor role
in the functionality of this protein.
PMID- 17041045
TI - Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis.
AB - Pseudomonas aeruginosa is a human opportunistic pathogen that chronically infects
the lungs of cystic fibrosis patients and is the leading cause of morbidity and
mortality of people afflicted with this disease. A striking correlation between
mutagenesis and the persistence of P. aeruginosa has been reported. In other well
studied organisms, error-prone replication by Y family DNA polymerases
contributes significantly to mutagenesis. Based on an analysis of the PAO1 genome
sequence, P. aeruginosa contains a single Y family DNA polymerase encoded by the
dinB gene. As part of an effort to understand the mechanisms of mutagenesis in P.
aeruginosa, we have cloned the dinB gene of P. aeruginosa and utilized a
combination of genetic and biochemical approaches to characterize the activity
and regulation of the P. aeruginosa DinB protein (DinB(Pa)). Our results indicate
that DinB(Pa) is a distributive DNA polymerase that lacks intrinsic proofreading
activity in vitro. Modest overexpression of DinB(Pa) from a plasmid conferred a
mutator phenotype in both Escherichia coli and P. aeruginosa. An examination of
this mutator phenotype indicated that DinB(Pa) has a propensity to promote C-->A
transversions and -1 frameshift mutations within poly(dGMP) and poly(dAMP) runs.
The characterization of lexA+ and DeltalexA::aacC1 P. aeruginosa strains,
together with in vitro DNA binding assays utilizing cell extracts or purified P.
aeruginosa LexA protein (LexA(Pa)), indicated that the transcription of the dinB
gene is regulated as part of an SOS-like response. The deletion of the dinB(Pa)
gene sensitized P. aeruginosa to nitrofurazone and 4-nitroquinoline-1-oxide,
consistent with a role for DinB(Pa) in translesion DNA synthesis over N2-dG
adducts. Finally, P. aeruginosa exhibited a UV-inducible mutator phenotype that
was independent of dinB(Pa) function and instead required polA and polC, which
encode DNA polymerase I and the second DNA polymerase III enzyme, respectively.
Possible roles of the P. aeruginosa dinB, polA, and polC gene products in
mutagenesis are discussed.
PMID- 17041046
TI - Differentiation and distribution of colistin- and sodium dodecyl sulfate-tolerant
cells in Pseudomonas aeruginosa biofilms.
AB - During Pseudomonas aeruginosa flow cell biofilm development, the cell population
differentiates into a nonmotile subpopulation which forms microcolonies and a
migrating subpopulation which eventually colonizes the top of the microcolonies,
resulting in the development of mushroom-shaped multicellular structures. The cap
forming subpopulation was found to develop tolerance to membrane-targeting
antimicrobial agents, such as the cyclic cationic peptide colistin and the
detergent sodium dodecyl sulfate. The stalk-forming subpopulation, on the other
hand, was sensitive to the membrane-targeting antibacterial agents. All biofilm
associated cells were sensitive to the antibacterial agents when tested in
standard plate assays. A mutation eliminating the production of type IV pili, and
hence surface-associated motility, prevented the formation of regular mushroom
shaped structures in the flow cell biofilms, and the development of tolerance to
the antimicrobial agents was found to be affected as well. Mutations in genes
interfering with lipopolysaccharide modification (pmr) eliminated the biofilm
associated colistin tolerance phenotype. Experiments with a PAO1 strain harboring
a pmr-gfp fusion showed that only the cap-forming subpopulation in biofilms
treated with colistin expresses the pmr operon. These results suggest that
increased antibiotic tolerance in biofilms may be a consequence of
differentiation into distinct subpopulations with different phenotypic
properties.
PMID- 17041047
TI - High-affinity binding of the staphylococcal HarA protein to haptoglobin and
hemoglobin involves a domain with an antiparallel eight-stranded beta-barrel
fold.
AB - Iron scavenging from the host is essential for the growth of pathogenic bacteria.
In this study, we further characterized two staphylococcal cell wall proteins
previously shown to bind hemoproteins. HarA and IsdB harbor homologous ligand
binding domains, the so called NEAT domain (for "near transporter") present in
several surface proteins of gram-positive pathogens. Surface plasmon resonance
measurements using glutathione S-transferase (GST)-tagged HarAD1, one of the
ligand binding domains of HarA, and GST-tagged full-length IsdB proteins
confirmed high-affinity binding to hemoglobin and haptoglobin-hemoglobin
complexes with equilibrium dissociation constants (K(D)) of 5 to 50 nM.
Haptoglobin binding could be detected only with HarA and was in the low
micromolar range. In order to determine the fold of this evolutionarily conserved
ligand binding domain, the untagged HarAD1 protein was subjected to nuclear
magnetic resonance spectroscopy, which revealed an eight-stranded, purely
antiparallel beta-barrel with the strand order (-beta1 -beta2 -beta3 -beta6
beta5 -beta4 -beta7 -beta8), forming two Greek key motifs. Based on structural
homology searches, the topology of the HarAD1 domain resembles that of the
immunoglobulin (Ig) fold family, whose members are involved in protein-protein
interactions, but with distinct structural features. Therefore, we consider that
the HarAD1/NEAT domain fold is a novel variant of the Ig fold that has not yet
been observed in other proteins.
PMID- 17041048
TI - NrrA directly regulates expression of hetR during heterocyst differentiation in
the cyanobacterium Anabaena sp. strain PCC 7120.
AB - Heterocyst differentiation in the cyanobacterium Anabaena sp. strain PCC 7120
requires NtcA, the global nitrogen regulator in cyanobacteria, and HetR, the
master regulator of heterocyst differentiation. Expression of hetR is upregulated
by nitrogen deprivation, and its upregulation depends on NtcA. However, it has
not yet been revealed how NtcA regulates the expression of hetR. In the
experiments presented here, it was confirmed that NrrA (All4312), a nitrogen
responsive response regulator, was required for the upregulation of hetR. The use
of the nitrogen-responsive transcription initiation sites (TISs) for the hetR
gene depended upon NrrA. NrrA bound specifically to the region upstream of TISs
located at positions -728 and -696 in vitro. Overexpression of nrrA resulted in
enhanced hetR expression and heterocyst formation. A molecular regulatory cascade
is proposed whereby NtcA upregulates the expression of nrrA upon limitation of
combined nitrogen in the medium and then NrrA upregulates the expression of hetR,
leading to heterocyst differentiation.
PMID- 17041049
TI - BadM is a transcriptional repressor and one of three regulators that control
benzoyl coenzyme A reductase gene expression in Rhodopseudomonas palustris.
AB - The rate-limiting enzyme of anaerobic benzoate degradation by Rhodopseudomonas
palustris, benzoyl coenzyme A (CoA) reductase, is highly sensitive to oxygen, and
its synthesis is tightly regulated. We determined that a previously unknown gene
in the benzoate gene cluster, badM, encodes a transcriptional repressor of
benzoyl-CoA reductase gene expression. BadM controls gene expression from the
benzoyl-CoA reductase promoter in concert with two previously described
transcriptional activators.
PMID- 17041050
TI - Inactivation of Lgt allows systematic characterization of lipoproteins from
Listeria monocytogenes.
AB - Lipoprotein anchoring in bacteria is mediated by the prolipoprotein
diacylglyceryl transferase (Lgt), which catalyzes the transfer of a
diacylglyceryl moiety to the prospective N-terminal cysteine of the mature
lipoprotein. Deletion of the lgt gene in the gram-positive pathogen Listeria
monocytogenes (i) impairs intracellular growth of the bacterium in different
eukaryotic cell lines and (ii) leads to increased release of lipoproteins into
the culture supernatant. Comparative extracellular proteome analyses of the EGDe
wild-type strain and the Delta lgt mutant provided systematic insight into the
relative expression of lipoproteins. Twenty-six of the 68 predicted lipoproteins
were specifically released into the extracellular proteome of the Delta lgt
strain, and this proved that deletion of lgt is an excellent approach for
experimental verification of listerial lipoproteins. Consequently, we generated
Delta lgt Delta prfA double mutants to detect lipoproteins belonging to the main
virulence regulon that is controlled by PrfA. Overall, we identified three
lipoproteins whose extracellular levels are regulated and one lipoprotein that is
posttranslationally modified depending on PrfA. It is noteworthy that in contrast
to previous studies of Escherichia coli, we unambiguously demonstrated that
lipidation by Lgt is not a prerequisite for activity of the lipoprotein-specific
signal peptidase II (Lsp) in Listeria.
PMID- 17041051
TI - Group B streptococcal pilus proteins contribute to adherence to and invasion of
brain microvascular endothelial cells.
AB - Surface filamentous structures known as pili have been discovered recently in the
gram-positive streptococcal pathogens that cause invasive disease in humans,
including group B Streptococcus (GBS). We show that two GBS proteins involved in
pilus formation, encoded by pilA and pilB, also facilitate the interaction of
this important agent of central nervous system infection with endothelial cells
of the human blood-brain barrier.
PMID- 17041052
TI - Expression of the pyr operon of Lactobacillus plantarum is regulated by inorganic
carbon availability through a second regulator, PyrR2, homologous to the
pyrimidine-dependent regulator PyrR1.
AB - Inorganic carbon (IC), such as bicarbonate or carbon dioxide, stimulates the
growth of Lactobacillus plantarum. At low IC levels, one-third of natural
isolated L. plantarum strains are nutritionally dependent on exogenous arginine
and pyrimidine, a phenotype previously defined as high-CO2-requiring (HCR)
prototrophy. IC enrichment significantly decreased the amounts of the enzymes in
the pyrimidine biosynthetic pathway encoded by the pyrR1BCAa1Ab1DFE operon, as
demonstrated by proteomic analysis. Northern blot and reverse transcription-PCR
experiments demonstrated that IC levels regulated pyr genes mainly at the level
of transcription or RNA stability. Two putative PyrR regulators with 62% amino
acid identity are present in the L. plantarum genome. PyrR1 is an RNA-binding
protein that regulates the pyr genes in response to pyrimidine availability by a
mechanism of transcriptional attenuation. In this work, the role of PyrR2 was
investigated by allelic gene replacement. Unlike the pyrR1 mutant, the DeltapyrR2
strain acquired a demand for both pyrimidines and arginine unless bicarbonate or
CO2 was present at high concentrations, which is known as an HCR phenotype.
Analysis of the IC- and pyrimidine-mediated regulation in pyrR1 and pyrR2 mutants
suggested that only PyrR2 positively regulates the expression levels of the pyr
genes in response to IC levels but had no effect on pyrimidine-mediated
repression. A model is proposed for the respective roles of PyrR1 and PyrR2 in
the pyr regulon expression.
PMID- 17041053
TI - 4-Chlorobenzoate uptake in Comamonas sp. strain DJ-12 is mediated by a tripartite
ATP-independent periplasmic transporter.
AB - The fcb gene cluster involved in the hydrolytic dehalogenation of 4
chlorobenzoate is organized in the order fcbB-fcbA-fcbT1-fcbT2-fcbT3-fcbC in
Comamonas sp. strain DJ-12. The genes are operonic and inducible with 4-chloro-,
4-iodo-, and 4-bromobenzoate. The fcbT1, fcbT2, and fcbT3 genes encode a
transporter in the secondary TRAP (tripartite ATP-independent periplasmic)
family. An fcbT1T2T3 knockout mutant shows a much slower growth rate on 4
chlorobenzoate compared to the wild type. 4-Chlorobenzoate is transported into
the wild-type strain five times faster than into the fcbT1T2T3 knockout mutant.
Transport of 4-chlorobenzoate shows significant inhibition by 4-bromo-, 4-iodo-,
and 4-fluorobenzoate and mild inhibition by 3-chlorobenzoate, 2-chlorobenzoate, 4
hydroxybenzoate, 3-hydroxybenzoate, and benzoate. Uptake of 4-chlorobenzoate is
significantly inhibited by ionophores which collapse the proton motive force.
PMID- 17041055
TI - Malonyl-coenzyme A reductase in the modified 3-hydroxypropionate cycle for
autotrophic carbon fixation in archaeal Metallosphaera and Sulfolobus spp.
AB - Autotrophic members of the Sulfolobales (Crenarchaeota) contain acetyl-coenzyme A
(CoA)/propionyl-CoA carboxylase as the CO2 fixation enzyme and use a modified 3
hydroxypropionate cycle to assimilate CO2 into cell material. In this central
metabolic pathway malonyl-CoA, the product of acetyl-CoA carboxylation, is
further reduced to 3-hydroxypropionate. Extracts of Metallosphaera sedula
contained NADPH-specific malonyl-CoA reductase activity that was 10-fold up
regulated under autotrophic growth conditions. Malonyl-CoA reductase was
partially purified and studied. Based on N-terminal amino acid sequencing the
corresponding gene was identified in the genome of the closely related
crenarchaeum Sulfolobus tokodaii. The Sulfolobus gene was cloned and
heterologously expressed in Escherichia coli, and the recombinant protein was
purified and studied. The enzyme catalyzes the following reaction: malonyl-CoA +
NADPH + H+ --> malonate-semialdehyde + CoA + NADP+. In its native state it is
associated with small RNA. Its activity was stimulated by Mg2+ and thiols and
inactivated by thiol-blocking agents, suggesting the existence of a cysteine
adduct in the course of the catalytic cycle. The enzyme was specific for NADPH
(Km = 25 microM) and malonyl-CoA (Km = 40 microM). Malonyl-CoA reductase has 38%
amino acid sequence identity to aspartate-semialdehyde dehydrogenase, suggesting
a common ancestor for both proteins. It does not exhibit any significant
similarity with malonyl-CoA reductase from Chloroflexus aurantiacus. This shows
that the autotrophic pathway in Chloroflexus and Sulfolobaceae has evolved
convergently and that these taxonomic groups have recruited different genes to
bring about similar metabolic processes.
PMID- 17041054
TI - Characterization of a highly conserved island in the otherwise divergent
Bordetella holmesii and Bordetella pertussis genomes.
AB - The recently discovered pathogen Bordetella holmesii has been isolated from the
airways and blood of diseased humans. Genetic events contributing to the
emergence of B. holmesii are not understood, and its phylogenetic position among
the bordetellae remains unclear. To address these questions, B. holmesii strains
were analyzed by comparative genomic hybridization (CGH) to a Bordetella
pertussis microarray and by multilocus sequence typing. Both methods indicated
substantial sequence divergence between B. pertussis and B. holmesii. However,
CGH identified a putative pathogenicity island of 66 kb that is highly conserved
between these species and contains several IS481 elements that may have been
laterally transferred from B. pertussis to B. holmesii. This island contains,
among other genes, a functional, iron-regulated locus encoding the biosynthesis,
export, and uptake of the siderophore alcaligin. The acquisition of this genomic
island by B. holmesii may have significantly contributed to its emergence as a
human pathogen. Horizontal gene transfer between B. pertussis and B. holmesii may
also explain the unusually high sequence identity of their 16S rRNA genes.
PMID- 17041056
TI - The UreEF fusion protein provides a soluble and functional form of the UreF
urease accessory protein.
AB - Four accessory proteins (UreD, UreE, UreF, and UreG) are typically required to
form the nickel-containing active site in the urease apoprotein (UreABC). Among
the accessory proteins, UreD and UreF have been elusive targets for biochemical
and structural characterization because they are not overproduced as soluble
proteins. Using the best-studied urease system, in which the Klebsiella aerogenes
genes are expressed in Escherichia coli, a translational fusion of ureE and ureF
was generated. The UreEF fusion protein was overproduced as a soluble protein
with a convenient tag involving the His-rich region of UreE. The fusion protein
was able to form a UreD(EF)G-UreABC complex and to activate urease in vivo, and
it interacted with UreD-UreABC in vitro to form a UreD(EF)-UreABC complex. While
the UreF portion of UreEF is fully functional, the fusion significantly affected
the role of the UreE portion by interrupting its dimerization and altering its
metal binding properties compared to those of the wild-type UreE. Analysis of a
series of UreEF deletion mutants revealed that the C terminus of UreF is required
to form the UreD(EF)G-UreABC complex, while the N terminus of UreF is essential
for activation of urease.
PMID- 17041057
TI - Identification of a gene negatively affecting antibiotic production and
morphological differentiation in Streptomyces coelicolor A3(2).
AB - SC7A1 is a cosmid with an insert of chromosomal DNA from Streptomyces coelicolor
A3(2). Its insertion into the chromosome of S. coelicolor strains caused a
duplication of a segment of ca. 40 kb and delayed actinorhodin antibiotic
production and sporulation, implying that SC7A1 carried a gene negatively
affecting these processes. The subcloning of SC7A1 insert DNA resulted in the
identification of the open reading frame SCO5582 as nsdA, a gene negatively
affecting Streptomyces differentiation. The disruption of chromosomal nsdA caused
the overproduction of spores and of three of four known S. coelicolor antibiotics
of quite different chemical types. In at least one case (that of actinorhodin),
this was correlated with premature expression of a pathway-specific regulatory
gene (actII-orf4), implying that nsdA in the wild-type strain indirectly
repressed the expression of the actinorhodin biosynthesis cluster. nsdA
expression was up-regulated upon aerial mycelium initiation and was strongest in
the aerial mycelium. NsdA has DUF921, a Streptomyces protein domain of unknown
function and a conserved SXR site. A site-directed mutation (S458A) in this site
in NsdA abolished its function. Blast searching showed that NsdA homologues are
present in some Streptomyces genomes. Outside of streptomycetes, NsdA-like
proteins have been found in several actinomycetes. The disruption of the nsdA
like gene SCO4114 had no obvious phenotypic effects on S. coelicolor. The nsdA
orthologue SAV2652 in S. avermitilis could complement the S. coelicolor nsdA-null
mutant phenotype.
PMID- 17041058
TI - Complete sequence analysis of novel plasmids from emetic and periodontal Bacillus
cereus isolates reveals a common evolutionary history among the B. cereus-group
plasmids, including Bacillus anthracis pXO1.
AB - The plasmids of the members of the Bacillus cereus sensu lato group of organisms
are essential in defining the phenotypic traits associated with pathogenesis and
ecology. For example, Bacillus anthracis contains two plasmids, pXO1 and pXO2,
encoding toxin production and encapsulation, respectively, that define this
species pathogenic potential, whereas the presence of a Bt toxin-encoding plasmid
defines Bacillus thuringiensis isolates. In this study the plasmids from B.
cereus isolates that produce emetic toxin or are linked to periodontal disease
were sequenced and analyzed. Two periodontal isolates examined contained almost
identical approximately 272-kb plasmids, named pPER272. The emetic toxin
producing isolate contained one approximately 270-kb plasmid, named pCER270,
encoding the cereulide biosynthesis gene cluster. Comparative sequence analyses
of these B. cereus plasmids revealed a high degree of sequence similarity to the
B. anthracis pXO1 plasmid, especially in a putative replication region. These
plasmids form a newly defined group of pXO1-like plasmids. However, these novel
plasmids do not contain the pXO1 pathogenicity island, which in each instance is
replaced by plasmid specific DNA. Plasmids pCER270 and pPER272 share regions that
are not found in any other pXO1-like plasmids. Evolutionary studies suggest that
these plasmids are more closely related to each other than to other identified B.
cereus plasmids. Screening of a population of B. cereus group isolates revealed
that pXO1-like plasmids are more often found in association with clinical
isolates. This study demonstrates that the pXO1-like plasmids may define
pathogenic B. cereus isolates in the same way that pXO1 and pXO2 define the B.
anthracis species.
PMID- 17041059
TI - Functional analysis of AtlA, the major N-acetylglucosaminidase of Enterococcus
faecalis.
AB - The major peptidoglycan hydrolase of Enterococcus faecalis, AtlA, has been
identified, but its enzyme activity remains unknown. We have used tandem mass
spectrometry analysis of peptidoglycan hydrolysis products obtained using the
purified protein to show that AtlA is an N-acetylglucosaminidase. To gain insight
into the regulation of its enzyme activity, the three domains of AtlA were
purified alone or in combination following expression of truncated forms of the
atlA gene in Escherichia coli or partial digestion of AtlA by proteinase K. The
central domain of AtlA was catalytically active, but its activity was more than
two orders of magnitude lower than that of the complete protein. Partial
proteolysis of AtlA was detected in vivo: zymograms of E. faecalis extracts
revealed two catalytically active protein bands of 62 and 72 kDa that were both
absent in extracts from an atlA null mutant. Limited digestion of AtlA by
proteinase K in vitro suggested that the proteolytic cleavage of AtlA in E.
faecalis extracts corresponds to the truncation of the N-terminal domain, which
is rich in threonine and glutamic acid residues. We show that the truncation of
the N-terminal domain from recombinant AtlA has no impact on enzyme activity. The
C-terminal domain of the protein, which contains six LysM modules bound to highly
purified peptidoglycan, was required for optimal enzyme activity. These data
indicate that AtlA is not produced as a proenzyme and that control of the AtlA
glucosaminidase activity is likely to occur at the level of LysM-mediated binding
to peptidoglycan.
PMID- 17041060
TI - Abortive infection mechanisms and prophage sequences significantly influence the
genetic makeup of emerging lytic lactococcal phages.
AB - In this study, we demonstrated the remarkable genome plasticity of lytic
lactococcal phages that allows them to rapidly adapt to the dynamic dairy
environment. The lytic double-stranded DNA phage ul36 was used to sequentially
infect a wild-type strain of Lactococcus lactis and two isogenic derivatives with
genes encoding two phage resistance mechanisms, AbiK and AbiT. Four phage mutants
resistant to one or both Abi mechanisms were isolated. Comparative analysis of
their complete genomes, as well as morphological observations, revealed that
phage ul36 extensively evolved by large-scale homologous and nonhomologous
recombination events with the inducible prophage present in the host strain. One
phage mutant exchanged as much as 79% of its genome compared to the core genome
of ul36. Thus, natural phage defense mechanisms and prophage elements found in
bacterial chromosomes contribute significantly to the evolution of the lytic
phage population.
PMID- 17041061
TI - N-acetylanthranilate amidase from Arthrobacter nitroguajacolicus Ru61a, an
alpha/beta-hydrolase-fold protein active towards aryl-acylamides and -esters, and
properties of its cysteine-deficient variant.
AB - N-acetylanthranilate amidase (Amq), a 32.8-kDa monomeric amide hydrolase, is
involved in quinaldine degradation by Arthrobacter nitroguajacolicus Ru61a.
Sequence analysis and secondary structure predictions indicated that Amq is
related to carboxylesterases and belongs to the alpha/beta-hydrolase-fold
superfamily of enzymes; inactivation of (His(6)-tagged) Amq by
phenylmethanesulfonyl fluoride and diethyl pyrocarbonate and replacement of
conserved residues suggested a catalytic triad consisting of S155, E235, and
H266. Amq is most active towards aryl-acetylamides and aryl-acetylesters.
Remarkably, its preference for ring-substituted analogues was different for
amides and esters. Among the esters tested, phenylacetate was hydrolyzed with
highest catalytic efficiency (k(cat)/K(m) = 208 mM(-1) s(-1)), while among the
aryl-acetylamides, o-carboxy- or o-nitro-substituted analogues were preferred
over p-substituted or unsubstituted compounds. Hydrolysis by His(6)Amq of primary
amides, lactams, N-acetylated amino acids, azocoll, tributyrin, and the
acylanilide and urethane pesticides propachlor, propham, carbaryl, and isocarb
was not observed; propanil was hydrolyzed with 1% N-acetylanthranilate amidase
activity. The catalytic properties of the cysteine-deficient variant
His(6)AmqC22A/C63A markedly differed from those of His(6)Amq. The replacements
effected some changes in K(m)s of the enzyme and increased k(cat)s for most aryl
acetylesters and some aryl-acetylamides by factors of about three to eight while
decreasing k(cat) for the formyl analogue N-formylanthranilate by several orders
of magnitude. Circular dichroism studies indicated that the cysteine-to-alanine
replacements resulted in significant change of the overall fold, especially an
increase in alpha-helicity of the cysteine-deficient protein. The conformational
changes may also affect the active site and may account for the observed changes
in kinetic properties.
PMID- 17041062
TI - Regulation of Aggregatibacter (Actinobacillus) actinomycetemcomitans leukotoxin
secretion by iron.
AB - The gram-negative oral and systemic pathogen Aggregatibacter (Actinobacillus)
actinomycetemcomitans produces a leukotoxin (LtxA) that is a member of the RTX
(repeats in toxin) family of secreted bacterial toxins. We have recently shown
that LtxA has the ability to lyse erythrocytes, which results in a beta-hemolytic
phenotype on Columbia blood agar. To determine if LtxA is regulated by iron, we
examined beta-hemolysis under iron-rich and iron-limiting conditions. Beta
hemolysis was suppressed in the presence of FeCl3. In contrast, strong beta
hemolysis occurred in the presence of the iron chelator deferoxamine. We found
that secretion of LtxA was completely inhibited by free iron, but expression of
ltxA was not regulated by iron. Free chromium, cobalt, and magnesium did not
affect LtxA secretion. Other LtxA-associated genes were not regulated by iron.
Thus, iron appears to play an important role in the regulation of LtxA secretion
in A. actinomycetemcomitans in a manner independent of gene regulation.
PMID- 17041063
TI - Membrane topology mapping of the Na+-pumping NADH: quinone oxidoreductase from
Vibrio cholerae by PhoA-green fluorescent protein fusion analysis.
AB - The membrane topologies of the six subunits of Na+-translocating NADH:quinone
oxidoreductase (Na+-NQR) from Vibrio cholerae were determined by a combination of
topology prediction algorithms and the construction of C-terminal fusions. Fusion
expression vectors contained either bacterial alkaline phosphatase (phoA) or
green fluorescent protein (gfp) genes as reporters of periplasmic and cytoplasmic
localization, respectively. A majority of the topology prediction algorithms did
not predict any transmembrane helices for NqrA. A lack of PhoA activity when
fused to the C terminus of NqrA and the observed fluorescence of the green
fluorescent protein C-terminal fusion confirm that this subunit is localized to
the cytoplasmic side of the membrane. Analysis of four PhoA fusions for NqrB
indicates that this subunit has nine transmembrane helices and that residue T236,
the binding site for flavin mononucleotide (FMN), resides in the cytoplasm. Three
fusions confirm that the topology of NqrC consists of two transmembrane helices
with the FMN binding site at residue T225 on the cytoplasmic side. Fusion
analysis of NqrD and NqrE showed almost mirror image topologies, each consisting
of six transmembrane helices; the results for NqrD and NqrE are consistent with
the topologies of Escherichia coli homologs YdgQ and YdgL, respectively. The
NADH, flavin adenine dinucleotide, and Fe-S center binding sites of NqrF were
localized to the cytoplasm. The determination of the topologies of the subunits
of Na+-NQR provides valuable insights into the location of cofactors and
identifies targets for mutagenesis to characterize this enzyme in more detail.
The finding that all the redox cofactors are localized to the cytoplasmic side of
the membrane is discussed.
PMID- 17041064
TI - Serological survey of encephalomyocarditis virus infection in pigs in France.
AB - Samples of serum from 76 gilts, 1440 sows, 1473 piglets and 3093 finishing pigs
from 96 farrow-to-finish herds were tested for antibodies to encephalomyocarditis
virus (EMCV) in microtitre serum neutralisation tests employing two strains of
virus, one associated with myocarditis and the other with reproductive failure.
The total seroprevalence of EMCV infection was 2.48 per cent. There was no
significant difference between the seroprevalence of the reproductive failure
strain (1.6 per cent) and the myocardial strain (1.85 per cent). The
seroprevalence was higher in the gilts (6.57 per cent) and sows (5.13 per cent)
than in the piglets (1 per cent) and finishing pigs (1.84 per cent), and the
highest titres were observed in the sows (1:540) and finishing pigs (1:640). In
the gilts, the difference in seroprevalence between the reproductive failure
strain (3.95 per cent) and the myocardial strain (5.33 per cent) was wider than
in the other groups.
PMID- 17041065
TI - Skeletal deformities and mortality in grey herons (Ardea cinerea) at Besthorpe
heronry, Nottinghamshire.
AB - Dead and sick grey heron chicks with multiple fractures of the leg and wing bones
and/or bone deformities have been reported at Besthorpe Nature Reserve heronry in
north Nottinghamshire since 1996. Forty-five grey heron carcases were examined,
35 from the Besthorpe colony and 10 from other colonies where bone disease was
not known to occur. On the basis of the results of radiological studies,
postmortem examinations, peripheral quantitative computed tomography scanning and
four-point bending tests, it was concluded that the skeletal abnormalities were
probably due to metabolic bone disease.
PMID- 17041066
TI - Production of prolific microsheep by embryo transfer into large non-prolific
sheep.
AB - The Garole is a prolific breed of microsheep that possesses the FecB gene, which
increases ovulation rate. The purpose of this study was to compare embryo
production by multiple ovulation in seven Garole ewes with that in seven normal
size, non-prolific Malpura ewes, and assess the influence of the large body size
of Awassi crossbred recipient ewes on the birth-weight of Garole lambs. Oestrus
was synchronised with two intramuscular injections of 7.5 mg prostaglandin
F(2alpha) administered 10 days apart. The donor ewes were superovulated by the
use of pregnant mare serum gonadotrophin and follicle-stimulating hormone. The
onset and duration of oestrus were similar in both breeds. The Garole donors had
higher total mean (se) ovarian responses (15.6 [3.6] v 9.1 [2.3]), ovulation rate
(13.6 [3.1] v 8.4 [2.2]) and produced more transferable embryos (6.0 [3.5] v 4.0
[0.9]) than the Malpura donors, but the differences were not statistically
significant. The Garole lambs produced by embryo transfer were on average 57.8
per cent heavier at birth than contemporary Garole lambs produced by natural
mating.
PMID- 17041067
TI - Evaluation of four manual tick-removal devices for dogs and cats.
PMID- 17041068
TI - Multiple endocrine neoplasia-like syndrome in a horse.
PMID- 17041069
TI - Isolation of EBLV-2 in a Daubenton's bat (Myotis daubentonii) found in
Oxfordshire.
PMID- 17041070
TI - MRSA in companion animals.
PMID- 17041071
TI - Treatment for fear of fireworks in dogs.
PMID- 17041072
TI - Modular RCVS certificates.
PMID- 17041073
TI - Prologue: combining research and reason to make treatment decisions.
PMID- 17041074
TI - Evidence-based practice: an examination of its ramifications for the practice of
speech-language pathology.
AB - PURPOSE: The purpose of this article is to consider some of the ramifications
that arise when a discipline newly endorses evidence-based practice (EBP) as a
primary guiding principle. Although EBP may appear straightforward, events
experienced by peer disciplines that have preceded us in the implementation of
EBP raise questions about defining acceptable forms of evidence for treatment
effectiveness and efficacy, the potential roles of nonspecific or common factors,
therapist quality in achieving therapy outcomes, and eventual applications of EBP
that may overly confine which treatments are considered acceptable and
reimbursable. METHOD: Through narrative review of the literature, the article
examines valuable as well as controversial features of EBP in addition to
obstacles that may impede the transition of evidence (research findings) to
clinical practice. CONCLUSION: EBP is a valuable construct in ensuring quality of
care. However, bridging between research evidence and clinical practice may
require us to confront potentially difficult issues and establish thoughtful
dialogue about best practices in fostering EBP itself.
PMID- 17041075
TI - Evidence-based practice in communication disorders: progress not perfection.
AB - PURPOSE: This commentary is written in response to a companion paper by Nan
Bernstein Ratner (Evidence-Based Practice: An Examination of its Ramifications
for the Practice of Speech-Language Pathology). METHOD: The comments reflect my
experience as Vice President for Research and Technology of the American Speech
Language-Hearing Association (ASHA). One of the responsibilities of the Vice
President is to monitor the work of the Advisory Committee on Evidence-Based
Practice. CONCLUSION: Evidence-based practice (EBP) is a challenging but
attainable goal for audiology and speech-language pathology. Our professions have
made rapid progress in developing the foundations for EBP. To be sure, a great
deal of work remains to be done, but we have learned from the experiences of
other professions and have built our own systems to support EBP.
PMID- 17041076
TI - Treatment decisions for children with speech-sound disorders.
AB - PURPOSE: In this article, I consider how research, clinical expertise, client
values, a clinician's theoretical perspective, and service delivery
considerations affect the decisions that clinicians make to treat children with
speech-sound disorders (SSD). METHOD: After reviewing the research on
phonological treatment, I discuss how a clinician's theoretical perspective
influences goal selection. Five perspectives are considered: (a) normative; (b)
bottom-up, discrete skill; (c) language-based; (d) broad-based; and (e)
complexity-based. The literature on treatment efficiency is then considered,
followed by a discussion of service delivery factors, client values, and
clinician factors. IMPLICATIONS: I believe like M. Ylvisaker (2004) that
treatment decisions are influenced the most by the changes that occur in client
behaviors. These changes must, however, be experimentally validated, which is not
always easy to do. M. Ylvisaker suggests that validation could take the form of
trial therapy, diagnostic teaching, or dynamic assessment, but it may also be
important to show that the treatment provided, not some other variable, was
primarily responsible for the behavioral change (A. Tyler, personal
communication, January 11, 2006).
PMID- 17041077
TI - Commentary on "treatment decisions for children with speech-sound disorders":
revisiting the past in EBP.
AB - PURPOSE: This commentary, written in response to Alan Kamhi's paper, "Treatment
Decisions for Children with Speech-Sound Disorders," further considers the "what"
or goal selection process of decision making with the aim of efficiency-getting
the most change in the shortest time. METHOD: My comments reflect a focus on the
client values piece of the evidence-based practice (EBP) triad through validating
treatment decisions for individual clients using generalization data. Such data
are ideal for demonstrating change according to specific benchmarks and
suggesting that treatment was responsible for this change. Consideration is also
given to deficit profiles and their implications for long-term outcomes when
validating the effects of treatment. CONCLUSION: Although the abundance of
evidence suggests that a variety of treatment approaches are effective for
children with speech-sound disorders, less is known about which are most
efficient as compared to one another or for which specific children.
Practitioners, however, are embracing EBP when they select a treatment by
matching the research evidence with a client's profile, collect systematic data,
and use those data to demonstrate that change is attributable to treatment.
PMID- 17041078
TI - Evidence-based practice, response to intervention, and the prevention of reading
difficulties.
AB - PURPOSE: This article provides an evidence-based perspective on what school
communities can do to lower the prevalence of reading difficulties among their
pupils through preventive interventions. It also delineates the roles that speech
language pathologists (SLPs) might play in these interventions. METHOD: This
article is organized to first provide a broad overview of current directions in
research, practice, and policy in educational interventions, with an emphasis on
how the three are increasingly integrated to respond to evidence showing that
American school children are underperforming in reading. Next, the concept of
response to intervention (RTI) is described. RTI is an educational policy and
practice that is grounded in the accumulated literature that focuses on how
schools might better organize themselves to deliver multitiered reading
interventions to reduce children's risk for reading disability. Last, this
article provides three organizational principles that school-based professionals,
including SLPs, might follow to deliver RTI interventions. IMPLICATIONS: This
article provides an important and timely description of key concepts in the
prevention of reading difficulties through proactive multitiered interventions.
SLPs can draw on the suggestions presented here to inform their local efforts in
implementing preventive literacy programs that are consistent with an RTI
paradigm.
PMID- 17041079
TI - The implications of RTI and EBP for SLPs: commentary on L. M. Justice.
AB - PURPOSE: This commentary responds to Justice's article on response to
intervention (RTI) and evidence-based practice (EBP) for reading instruction. The
educational changes brought about by RTI and EBP provide an opportunity as well
as a challenge for speech-language pathologists (SLPs) to make fundamental
changes in service delivery. METHOD: In this article, I discuss how RTI will
change who qualifies as reading disabled and who receives special reading
instruction. I examine how RTI might change who qualifies and how they qualify
for speech-language services. Finally, I consider what can be taken from EPB and
RTI to improve speech-language service delivery. CONCLUSION: RTI has the
potential to fundamentally change regular education and its interface with
special education. If SLP clinicians, researchers, and policymakers recognize the
possibilities, RTI could also significantly and positively impact educational
speech-language pathology.
PMID- 17041080
TI - Making evidence-based decisions about child language intervention in schools.
AB - PURPOSE: The results of recent survey studies suggest that speech-language
pathologists base most of their clinical decisions on information they were
taught during their graduate programs, their clinical experience, and the
opinions of colleagues (T. Wolf & J. Balderson, 2005; R. Zipoli & M. Kennedy,
2005). This is contrary to the principles of evidence-based practice (EBP), in
which clinical decisions arise from the integration of scientific evidence,
clinician experience, and client needs. Our field's interest in EBP is relatively
young. Currently, there are no published committee-derived EBP guidelines for
providing language intervention services for children with language disorders.
Until national or international organizations publish recommendations from EBP
guideline writing panels, clinicians will need to make personal evidence-based
decisions with relatively little assistance from outside sources. The purpose of
this article is to summarize a seven-step process for making local EBP decisions.
METHOD: The authors provide information about a method for forming clinical
questions, finding relevant scientific studies, and evaluating those studies that
requires relatively little time and few external resources. The authors also
provide a system for integrating scientific evidence with their own expertise and
training within the context of their employment settings. Finally, an example is
provided to show clinicians how to use the evidence-based decision-making process
to answer a clinical question about clinical methods for improving grammatical
morphology in children with speech-language impairment. CONCLUSION: It is
possible for clinicians to make time- and resource-efficient evidence-based
decisions that integrate scientific evidence, clinical expertise, and student
parent preferences.
PMID- 17041081
TI - Commentary on "making evidence-based decisions about child language intervention
in schools" by Gillam and Gillam.
AB - PURPOSE: This paper is a personal reaction to Gillam and Gillam's treatise on
evidence-based decision making in schools. This evaluation focuses principally on
the costs and benefits of clinicians' search for external evidence, potential
problems associated with efforts to grade that evidence, and the integration of
this evidence with "internal" evidence related to specific children and their
families, clinician preferences and experience, and the school setting. METHOD:
Descriptive methods (that are not evidence-based) are used to evaluate critically
Gillam and Gillam's proposals on the implementation of evidence-based practice
(EBP) in schools. CONCLUSION: Early efforts to implement the plan for EBP
illustrated by Gillam and Gillam are likely to be difficult, forcing clinicians
to be flexible and patient. Nevertheless, if the plan is followed, it will result
ultimately in improved speech-language pathology services in the schools and
improved clinical research to support those services.
PMID- 17041082
TI - Epilogue: some final thoughts on EBP.
AB - PURPOSE: In this afterward, I will offer some final thoughts on this clinical
forum by considering a central question of EBP--how experimental validation is
defined--to illustrate the difficulty involved in implementing EBP. METHOD: The
comments draw on critical reviews I have received on my article in this forum and
conversations I have had with professional colleagues about EBP. CONCLUSION: Like
most scientific constructs, EBP is open to different interpretations. At their
worst, these differences have the potential to polarize clinical practice. The
hope, however, as Kent and Fey have expressed, is that articles and commentaries
such as these will serve as the basis for discussion and even argument among
clinicians and researchers as we attempt to define a philosophy and
implementation of EBP suited to our profession.
PMID- 17041083
TI - Which orthodontic archwire sequence? A randomized clinical trial.
AB - The aim of this study was to compare three orthodontic archwire sequences. One
hundred and fifty-four 10- to 17-year-old patients were treated in three centres
and randomly allocated to one of three groups: A = 0.016-inch nickel titanium
(NiTi), 0.018 x 0.025-inch NiTi, and 0.019 x 0.025-inch stainless steel (SS); B =
0.016-inch NiTi, 0.016-inch SS, 0.020-inch SS, and 0.019 x 0.025-inch SS; and C =
0.016 x 0.022-inch copper (Cu) NiTi, 0.019 x 0.025-inch CuNiTi, and 0.019 x 0.025
inch SS. At each archwire change and for each arch, the patients completed
discomfort scores on a seven-point Likert scale at 4 hours, 24 hours, 3 days, and
1 week. Time in days and the number of visits taken to reach a 0.019 x 0.025-inch
SS working archwires were calculated. A periapical radiograph of the upper left
central incisor was taken at the start of the treatment and after placement of
the 0.019 x 0.025-inch SS wire so root resorption could be assessed. There were
no statistically significant differences between archwire sequences A, B, or C
for patient discomfort (P > 0.05) or root resorption (P = 0.58). The number of
visits required to reach the working archwire was greater for sequence B than for
A (P = 0.012) but this could not be explained by the increased number of
archwires used in sequence B.
PMID- 17041084
TI - The clinical features and aetiological basis of primary eruption failure.
AB - Primary failure of eruption (PFE) is a poorly understood condition associated
with tooth eruption failure. This investigation systematically reviews the
literature, evaluates clinical features and associations with PFE, and describes
five further cases. Publications were selected and identified as describing PFE
when there was no identifiable aetiological factor contributing to eruption
failure and no evidence of successful orthodontic extrusion of the affected tooth
or teeth. A data abstraction form recorded the following additional information;
subject age, gender, general health status, and teeth present. Eighteen
publications were sourced that detailed at least one case of PFE in a manner
conforming to the selection criteria; these papers included a total of 35
individual cases, to which five previously unreported subjects were added. Within
the whole sample of 40 cases, a total of 24 (60 per cent) were females and 16 (40
per cent) males. First and second molar teeth were most commonly affected;
incisors, canines, and premolars were also involved, but with a reduced
individual frequency. There was no significant difference in incidence between
the maxilla and mandible, or between left and right sides. A family history of
eruption failure was found in almost 50 per cent of the sample, with eruption
failure or ankylosis affecting at least one primary tooth, also a common finding.
Within the 40 cases, hypodontia was present at levels higher than population
norms. PFE appears to be a condition that predominantly affects the molar
dentition. The increased frequency of hypodontia in affected individuals and
common findings of a family history regarding tooth eruption problems suggests a
significant genetic component to the aetiology of this rare condition.
PMID- 17041085
TI - Orthognathic treatment: how much does it cost?
AB - The aim of this multi-centre retrospective study was to assess the cost, and
factors influencing the cost, of combined orthodontic and surgical treatment for
dentofacial deformity. The sample, from the south-west of England, comprised 352
subjects (109 males and 243 females) with an age range of 14 to 57 years treated
in 11 hospital orthodontic units. Treatment costs were calculated for each
subject by combining consumable costs with staff overhead and capital costs. The
median total treatment cost was euro 6075.25 (interquartile range: euro 5139.41
euro 7069.68). Out-patient costs comprised 43 per cent. The median orthodontic
treatment costs were euro 1456.23 (interquartile range: euro 1283.73-euro
1638.75). Orthodontic costs on average comprised 25 per cent of the total
treatment cost. The cost of orthodontics for orthognathic patients in a hospital
setting appears to represent excellent value for the state funded National Health
Service in the United Kingdom.
PMID- 17041086
TI - Tumor models for efficacy determination.
AB - The first in vivo tumor models were developed in the mid-1960s. These models were
mouse leukemia models grown as ascites. The growth pattern was like that of
bacteria in vivo and therefore it was possible to apply similar mathematics of
growth and response to these tumors as had been worked out for bacteria. Since
the development of the murine leukemia models, investigators have devoted a large
effort to modeling solid tumors in mice. There are now a variety of models
including syngeneic mouse tumors and human tumor xenografts grown as s.c.
nodules, syngeneic mouse tumors and human tumor xenografts grown in orthotopic
sites, models of disseminated disease, "labeled" tumor models that can be
visualized using varied technologies, and transgenic tumor models. Each of these
types of models has advantages and disadvantages to the "drug hunter" searching
for improved treatments.
PMID- 17041087
TI - Developing gene expression signatures of pathway deregulation in tumors.
AB - Recent advances in our understanding of cancer biology have led to the
development of therapies targeting specific signaling pathways. Molecular
targeting promises to improve our ability to predict who will respond by
assessing the state of these targeted pathways in patients. However, a single
pathway can be deregulated by multiple mechanisms, and for some pathways it may
be difficult to assess activation state by analyzing a single oncogene or tumor
suppressor. Therefore, developing gene expression signatures of pathway
activation status using model systems or human tumor samples may enable a more
reliable measurement of pathway activity. This review discusses recent advances
in the identification of gene expression-based signatures of pathway deregulation
and how this information may lead to improved therapeutic response prediction.
PMID- 17041088
TI - Comparing Aurora A and Aurora B as molecular targets for growth inhibition of
pancreatic cancer cells.
AB - To address the increased need to understand the similarities and differences in
targeting Aurora A or Aurora B for the treatment of cancer, we systematically
evaluated the relative importance of Aurora A and/or Aurora B as molecular
targets using antisense oligonucleotides. It was found that perturbations in
Aurora A and Aurora B signaling result in growth arrest and apoptosis
preferentially in cancer cells. The biological fingerprints of Aurora A and
Aurora B inhibition were compared and contrasted in efforts to identify the
superior therapeutic target. Due to the different biological responses, we
conclude that each Aurora kinase should be treated as autonomous drug targets,
which can be targeted independently or in combination. We observed no advantages
to targeting both kinases simultaneously and feel that an Aurora A-targeted
therapy may have some beneficial consequences over an Aurora B-targeted therapy,
such as mitotic arrest and the rapid induction of apoptosis.
PMID- 17041089
TI - Role of the ABCG2 drug transporter in the resistance and oral bioavailability of
a potent cyclin-dependent kinase/Aurora kinase inhibitor.
AB - Cell cycle kinase inhibitors have advanced into clinical trials in oncology. One
such molecule, JNJ-7706621, is a broad-spectrum inhibitor of the cyclin-dependent
kinases and Aurora kinases that mediate G(2)-M arrest and inhibits tumor growth
in xenograft models. To determine the putative mechanisms of resistance to JNJ
7706621 that might be encountered in the clinic, the human epithelial cervical
carcinoma cell line (HeLa) was exposed to incrementally increasing concentrations
of JNJ-7706621. The resulting resistant cell population, designated HeLa-6621,
was 16-fold resistant to JNJ-7706621, cross-resistant to mitoxantrone (15-fold)
and topotecan (6-fold), and exhibited reduced intracellular drug accumulation of
JNJ-7706621. ABCG2 was highly overexpressed at both the mRNA ( approximately 163
fold) and protein levels. The functional role of ABCG2 in mediating resistance to
JNJ-7706621 was consistent with the following findings: (a) an ABCG2 inhibitor,
fumitremorgin C, restored the sensitivity of HeLa-6621 cells to JNJ-7706621 and
to mitoxantrone; (b) human embryonic kidney-293 cells transfected with ABCG2 were
resistant to both JNJ-7706621 and mitoxantrone; and (c) resistant cells that were
removed from the drug for 12 weeks and reverted to susceptibility to JNJ-7706621
showed near-normal ABCG2 RNA levels. ABCG2 is likely to limit the bioavailability
of JNJ-7706621 because oral administration of JNJ-7706621 to Bcrp (the murine
homologue of ABCG2) knockout mice resulted in an increase in the plasma
concentration of JNJ-7706621 compared with wild-type mice. These findings
indicate that ABCG2 mediates the resistance to JNJ-7706621 and alters the
absorption of the compound following administration.
PMID- 17041090
TI - Differing effects of microtubule depolymerizing and stabilizing chemotherapeutic
agents on t-SNARE-mediated apical targeting of prostate-specific membrane
antigen.
AB - Prostate-specific membrane antigen (PSMA) is a protein up-regulated in the vast
majority of prostate cancers. Antibodies to PSMA have proved highly specific for
prostate cancer cells, and the therapeutic potential of such antibodies is
currently being assessed in clinical trials. We have previously shown that PSMA
at the cell surface of polarized epithelial cells is predominantly expressed at
the apical plasma membrane and that microtubule depolymerization abolishes apical
PSMA targeting. In the current report, we implicate a functional role for a
target membrane soluble N-ethylmaleimide-sensitive factor adaptor protein
receptor, syntaxin 3, in the microtubule-dependent apical targeting of PSMA. PSMA
and syntaxin 3 are similarly localized to the apical plasma membrane of the
prostatic epithelium and Madin-Darby canine kidney cells. Introduction of a point
mutation into syntaxin 3 abolishes its polarized distribution and causes PSMA to
be targeted in a nonpolarized fashion. Additionally, treatment of polarized Madin
Darby canine kidney cells with vinblastine, a microtubule depolymerizing
chemotherapeutic agent, causes both syntaxin 3 and PSMA to redistribute in a
nonpolarized fashion. However, following treatment with the microtubule
stabilizing chemotherapeutic agent Taxotere, both syntaxin 3 and PSMA continue to
localize in a polarized manner at the apical plasma membrane. Thus, microtubule
depolymerizing and stabilizing chemotherapeutic drugs might exact similar
cytotoxic effects but have disparate effects on protein targeting. This
phenomenon might have important clinical implication, especially related to
antibody-mediated immunotherapy, and could potentially be exploited for
therapeutic benefit.
PMID- 17041091
TI - Dimerization of CXCR4 in living malignant cells: control of cell migration by a
synthetic peptide that reduces homologous CXCR4 interactions.
AB - Chemokine receptor CXCR4 (CD184) may play a role in cancer metastasis and is
known to form homodimers. However, it is not clear how transmembrane regions (TM)
of CXCR4 and receptor homotypic interactions affect the function of CXCR4 in
living cells. Using confocal microscopy and flow cytometric analysis, we showed
that high levels of CXCR4 are present in the cytoplasm, accompanied by lower
expression on the cell surface in CXCR4 transfectants, tumor cells, and normal
peripheral blood lymphocytes. CXCR4 homodimers were detected in tumor cells, both
on the cell surface membrane and in the cytoplasm using fluorescence resonance
energy transfer and photobleaching fluorescence resonance energy transfer to
measure energy transfer between CXCR4-CFP and CXCR4-YFP constructs. Disruption of
lipid rafts by depletion of cholesterol with methyl-beta-cyclodextrin reduced the
interaction between CXCR4 molecules and inhibited malignant cell migration to
CXCL12/SDF-1alpha. A synthetic peptide of TM4 of CXCR4 reduced energy transfer
between molecules of CXCR4, inhibited CXCL12-induced actin polymerization, and
blocked chemotaxis of malignant cells. TM4 also inhibited migration of normal
monocytes toward CXCL12. Reduction of CXCR4 energy transfer by the TM4 peptide
and methyl-beta-cyclodextrin indicates that interactions between CXCR4s may play
important roles in cell migration and suggests that cell surface and
intracellular receptor dimers are appropriate targets for control of tumor cell
spread. Targeting chemokine receptor oligomerization and signal transduction for
the treatment of cancer, HIV-1 infections, and other CXCR4 mediated inflammatory
conditions warrants further investigation.
PMID- 17041092
TI - Inhibition of cell growth and nuclear factor-kappaB activity in pancreatic cancer
cell lines by a tylophorine analogue, DCB-3503.
AB - A tylophorine analogue, DCB-3503, has been shown to have potent activity against
tumor growth in vitro and in vivo, as well as activity in an autoimmune disease
model in vivo. This study focuses on investigating the mechanisms responsible for
antitumor activity of DCB-3503. The concentrations for inhibiting 50%
growth/colony formation ability are 50/162 and 40/149 nmol/L for PANC-1 and HPAC
cells, respectively. The growth inhibition effects are associated with DCB-3503
induced reprogramming of tumor cells. DCB-3503 could interfere with cell cycle
progression. Several cell cycle regulatory proteins, including cyclin D(1), are
down-regulated by DCB-3503. Using several different transcription elements
coupled with a reporter gene, it was found that the nuclear factor-kappaB (NF
kappaB) signaling pathway is the most sensitive pathway mediator affected by DCB
3503. The inhibition of NF-kappaB activity is dependent on the down-regulation of
nuclear phosphorylated p65, a component of the active form of the NF-kappaB
complex. Such a decrease in nuclear phosphorylated p65 can be reversed by a
proteosome inhibitor. Furthermore, the activity and protein expression of nuclear
IkappaB kinase alpha, which is responsible for p65 phosphorylation, is suppressed
and down-regulated in cells treated with DCB-3503. In summary, DCB-3503 could
affect cell cycle regulatory proteins and is a potent modulator of NF-kappaB
function. It is a potentially useful compound in the management of cancers in
which cyclin D1 overexpression and high NF-kappaB activity play a pivotal role.
PMID- 17041093
TI - Signaling interactions of rapamycin combined with erlotinib in cervical carcinoma
xenografts.
AB - Clinical trials using rapamycin analogues or HER1/epidermal growth factor
receptor (EGFR) inhibitors show that each class of agent has activity against a
range of human solid tumors. Because blockade of mitogen-activated protein kinase
signaling occurs following HER1/EGFR inhibition in some cell types, we tested the
combination of rapamycin and erlotinib in SiHa, Me180, and CaSki human cervical
carcinomas xenografts in severe combined immunodeficient mice. In tissue culture,
all three cell lines showed decreased phosphorylated S6 ribosomal protein and
decreased phosphorylated extracellular signal-regulated kinase (ERK) following
treatment with rapamycin and erlotinib, respectively. In SiHa tumors, suppression
of phosphorylated S6 was induced by either drug alone, whereas phosphorylated ERK
decreased with erlotinib, and enhancement of these effects was obtained with the
combination. Continuous treatment of xenografts for 3 weeks led to significant
tumor growth delay compared with vehicle control for rapamycin as single agent (P
= 0.003) and greater for the combination (P = 0.04 versus rapamycin). Significant
antiangiogenic effect was obtained in SiHa xenografts using the drugs together
(measured by microvascular density and vascular endothelial growth factor plasma
levels) but not for the single agents. Me180 and CaSki xenografts showed
significant growth delay with rapamycin but not with erlotinib. Erlotinib
treatment resulted in decreased phosphorylated ERK, associated with enhanced
suppression of phosphorylated S6 and improved growth delay in Me180 but not in
CaSki tumors. These results support the further clinical investigation of
rapamycin and EGFR inhibitor combinations in anticancer therapy but highlight the
problem of intertumoral heterogeneity in the prediction of in vivo response.
PMID- 17041094
TI - Expression of a suicidal gene under control of the human secreted protein acidic
and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the
inhibition of tumor cell growth.
AB - The successful use of transcriptional targeting for cancer therapy depends on the
activity of a given promoter inside the malignant cell. Because solid human
tumors evolve as a "cross-talk" between the different cell types within the
tumor, we hypothesized that targeting the entire tumor mass might have better
therapeutic effect. Secreted protein acidic and rich in cysteine (SPARC) is a
matricellular protein overexpressed in different human cancers malignant
melanomas both in the malignant cells compartment as in the stromal one
(fibroblasts and endothelial cells). We have shown that expression of the herpes
simplex virus-thymidine kinase (TK) gene driven by the SPARC promoter in
combination with ganciclovir inhibited human melanoma cell growth in monolayer as
well as in multicellular spheroids. This inhibitory effect was observed both in
homotypic spheroids composed of melanoma cells alone as well as in spheroids made
of melanoma cells and stromal cells. Expression of the TK gene was also efficient
to inhibit the in vivo tumor growth of established melanomas when TK was
expressed either by the malignant cells themselves or by coadministered
endothelial cells. Our data suggest that the use of therapeutic genes driven by
SPARC promoter could be a valuable strategy for cancer therapy aiming to target
all the cellular components of the tumor mass.
PMID- 17041095
TI - Reverse phase protein array: validation of a novel proteomic technology and
utility for analysis of primary leukemia specimens and hematopoietic stem cells.
AB - Proteomics has the potential to provide answers in cancer pathogenesis and to
direct targeted therapy through the comprehensive analysis of protein expression
levels and activation status. The realization of this potential requires the
development of new, rapid, high-throughput technologies for performing protein
arrays on patient samples, as well as novel analytic techniques to interpret
them. Herein, we describe the validation and robustness of using reverse phase
protein arrays (RPPA) for the analysis of primary acute myelogenous leukemia
samples as well as leukemic and normal stem cells. In this report, we show that
array printing, detection, amplification, and staining precision are very high,
reproducible, and that they correlate with traditional Western blotting. Using
replicates of the same sample on the same and/or separate arrays, or using
separate protein samples prepared from the same starting sample, the intra- and
interarray reproducibility was extremely high. No statistically significant
difference in protein signal intensities could be detected within the array
setups. The activation status (phosphorylation) was maintained in experiments
testing delayed processing and preparation from multiple freeze-thawed samples.
Differences in protein expression could reliably be detected in as few as three
cell protein equivalents. RPPA prepared from rare populations of normal and
leukemic stem cells were successfully done and showed differences from bulk
populations of cells. Examples show how RPPAs are ideally suited for the large
scale analysis of target identification, validation, and drug discovery. In
summary, RPPA is a highly reliable, reproducible, high-throughput system that
allows for the rapid large-scale proteomic analysis of protein expression and
phosphorylation state in primary acute myelogenous leukemia cells, cell lines,
and in human stem cells.
PMID- 17041096
TI - The antitumor effects of sunitinib (formerly SU11248) against a variety of human
hematologic malignancies: enhancement of growth inhibition via inhibition of
mammalian target of rapamycin signaling.
AB - We studied antitumor effects of receptor tyrosine kinase inhibitor sunitinib
(formerly SU11248) against a variety of hematologic malignancies including the
following leukemias: eosinophilic (EOL-1), acute myeloid (THP-1, U937, Kasumi-1),
biphenotypic (MV4-11), acute lymphoblastic (NALL-1, Jurkat, BALL-2, PALL-1, PALL
2), blast crisis of chronic myeloid (KU812, Kcl-22, K562), and adult T-cell (MT
1, MT-2, MT-4), as well as non-Hodgkin's lymphoma (KS-1, Dauji, Akata) and
multiple myeloma (U266). Thymidine uptake studies showed that sunitinib was
active against EOL-1, MV4-11, and Kasumi-1 cells, which possessed activating
mutations of the PDGFRalpha, FLT-3, and c-KIT genes, respectively, with IC(50)s
of <30 nmol/L. In addition, sunitinib inhibited the proliferation of freshly
isolated leukemia cells from patients possessing mutations in FLT3 gene. Annexin
V staining showed that sunitinib induced apoptosis of these cells. Sunitinib
inhibited phosphorylation of FLT3 and PDGFRalpha in conjunction with blockade of
mammalian target of rapamycin signaling in MV4-11 and EOL-1 cells, respectively.
Interestingly, rapamycin analogue RAD001 enhanced the ability of sunitinib to
inhibit the proliferation of leukemia cells and down-regulate levels of mammalian
target of rapamycin effectors p70 S6 kinase and eukaryotic initiation factor 4E
binding protein 1 in these cells. Taken together, sunitinib may be useful for
treatment of individuals with leukemias possessing activation mutation of
tyrosine kinase, and the combination of sunitinib and RAD001 represents a
promising novel treatment strategy.
PMID- 17041097
TI - Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant
glioma.
AB - Promoter hypermethylation of the DNA repair protein O(6)-alkylguanine-DNA
alkyltransferase (AGT) has been associated with an enhanced response to
chloroethylating and methylating agents in patients with malignant glioma. The
purpose of this study was to compare three distinct yet related indices for
measuring AGT to determine if these assays could be used interchangeably when AGT
status is to be used to guide chemotherapeutic decisions. Real-time methylation
specific PCR (MSP), assessed as the ratio of methylated AGT copies to internal
beta-actin control, was used to quantitate AGT hypermethylation in 32 glioma
samples. Data were compared with AGT enzyme activity as well as
immunohistochemical detection of AGT protein from the same samples.
Hypermethylation of the AGT promoter was detected in 19 of 31 (61%) samples
evaluable by MSP. Low-level AGT, defined as <20% nuclear AGT staining by
immunohistochemistry, was found in 10 of 32 samples (31%), whereas 12 of 32 (38%)
had low levels of AGT activity. Correlation of immunohistochemistry to AGT
activity was statistically significant (P = 0.014) as was the correlation of
immunohistochemistry to MSP (P = 0.043), whereas MSP compared with AGT activity
(P = 0.246) was not significant. Cross-tabulation of immunohistochemistry and MSP
data based on prognostic groups, where good prognosis was represented by an
immunohistochemistry of <20% and an MSP ratio >12, showed no significant
relationship (P = 0.214), suggesting that one assay cannot be used
interchangeably for another. The observed discordance between respective measures
of AGT based on prognosis supports further standardization of AGT assays designed
to guide therapeutic practice. The data also suggest that consideration be given
to the large population of AGT-expressing cells within samples when therapeutic
strategies based on tumor methylation are used.
PMID- 17041099
TI - The effect of a novel transition state inhibitor of methylthioadenosine
phosphorylase on pemetrexed activity.
AB - Pemetrexed is a new-generation antifolate inhibitor of thymidylate synthase (TS)
and a weaker inhibitor of glycinamide ribonucleotide transformylase (GARFT)
required for de novo purine synthesis. Methylthioadenosine phosphorylase (MTAP)
salvages purines by releasing adenine from methylthioadenosine and is often
deleted in mesothelioma. The current study addresses the effect of MTAP on
pemetrexed activity using a highly potent transition state inhibitor of MTAP, MT
DADMe-Immucillin A (ImmA; K(i) = 86 pmol/L) in the MTAP(+) NCI-H28 and MTAP(-)
NCI-H2052 mesothelioma cell lines. Based on selective nucleoside protection, TS
was found to be the primary pemetrexed target in both cell lines with GARFT
inhibition requiring 20- to 30-fold higher pemetrexed concentrations. ImmA had no
effect on pemetrexed activity but, when thymidine was added, the pemetrexed
IC(50) decreased by a factor of approximately 3 in MTAP(+) H28 cells with no
effect in MTAP(-) H2052 cells. Conversely, the transfection of MTAP into H2052
cells increased the pemetrexed IC(50) by nearly 3-fold but only in the presence
of thymidine; this was reversed by ImmA. An MTAP-specific short interfering RNA
produced a 2-fold decrease in pemetrexed IC(50) in MTAP(+) HeLa cells in the
presence of thymidine. These data indicate that suppression of constitutive MTAP
has no effect on pemetrexed activity when the primary target is TS. There is a
modest salutary effect when the pemetrexed target is GARFT alone.
PMID- 17041098
TI - The mechanism of methylselenocysteine and docetaxel synergistic activity in
prostate cancer cells.
AB - The study was designed to evaluate the combination treatment of
methylselenocysteine (MSeC) and docetaxel and to delineate the underlying
mechanism associated with observed in vitro synergy between MSeC and docetaxel in
prostate cancer cells. Cells were treated with different concentrations and
schedules (concurrent or sequential) of MSeC and docetaxel alone or in
combination. Cell growth/death was assessed with sulforhodamine B assay, trypan
blue assay, and time-lapse video. Loewe synergism/antagonism model was used to
determine whether the combination effect was additive, synergistic, or
antagonistic. Apoptosis and caspase-3 activity were evaluated with cell death
ELISA assay and caspase activity assay, respectively. Synergy between MSeC and
docetaxel was further assessed in the presence and absence of z-VAD-fmk, a pan
caspase inhibitor. Effect of MSeC and docetaxel alone or in combination on the
cellular expression of the antiapoptotic protein survivin was measured with
Western blot analyses. Pretreatment with MSeC was crucial to enhance docetaxel
antitumor activity. The enhanced antitumor activity of the sequential combination
treatment of MSeC and docetaxel (MSeC/docetaxel) was highly synergistic.
Apoptosis increased after MSeC/docetaxel, compared with each drug alone or
concurrent treatment. Pretreatment with z-VAD-fmk converted the synergy into
antagonism, suggesting that the synergy is caspase-dependent apoptosis. The
survivin level was down-regulated following MSeC/docetaxel treatment when
compared with each drug alone. In conclusion, pretreatment with MSeC was
essential to markedly sensitize cells to docetaxel. The synergy between MSeC and
docetaxel in C2G prostate cancer cells is associated with increased level of
caspase-dependent apoptosis and decreased level of survivin.
PMID- 17041100
TI - A urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many
human tumor cell types.
AB - Urokinase plasminogen activator (uPA) is a tumor-specific protease highly
expressed in several types of solid tumors and rarely present on normal cells
under physiologic conditions. Due to its high expression on metastatic tumors,
several different strategies have been used to target the urokinase system. These
have mostly led to tumor growth inhibition rather than tumor regression. A
different approach was adopted by replacing the furin activation site on a
recombinant anthrax toxin with a urokinase activation site. The resulting toxin,
PrAgU2/FP59, was highly potent against tumors both in vitro and in vivo. In this
study, we show that PrAgU2/FP59 is toxic to a wide range of tumor cell lines,
including non-small cell lung cancer, pancreatic cancer, and basal-like breast
cancer cell lines. Of the few cell lines found to be resistant to PrAgU2/FP59,
most became sensitive upon addition of exogenous pro-uPA. PrAgU2/FP59 was much
less toxic to normal human cells. The potency of PrAgU2/FP59 was dependent on
anthrax toxin receptor, uPA receptor, and uPA levels but not on total plasminogen
activator inhibitor-1 levels. In this study, we show that PrAgU2/FP59 is a wide
range, highly potent, and highly selective toxin that is capable of specifically
targeting uPA-expressing tumor cells, independently of the tissue of origin of
these cells. Furthermore, we identify three molecular markers, anthrax toxin
receptor, uPA, and uPA receptor, which can be used as predictors of tumor cell
sensitivity to PrAgU2/FP59.
PMID- 17041101
TI - Synthesis and biological analysis of new curcumin analogues bearing an enhanced
potential for the medicinal treatment of cancer.
AB - Curcumin (diferuloylmethane) is a dietary phytochemical with low toxicity that
exhibits growth-suppressive activity against a variety of cancer cells and
possesses certain chemopreventive properties. Curcumin has already been the
subject of several clinical trials for use as a treatment in human cancers.
Synthetic chemical modifications of curcumin have been studied intensively in an
attempt to find a molecule with similar but enhanced properties of curcumin. In
this study, a series of novel curcumin analogues were synthesized and screened
for anticancer activity. New analogues that exhibit growth-suppressive activity
30 times that of curcumin and other commonly used anticancer drugs were
identified. Structurally, the new analogues are symmetrical 1,5
diarylpentadienone whose aromatic rings possess an alkoxy substitution at each of
the positions 3 and 5. Analysis of the effects of the analogues on the expression
of cancer-related genes usually affected by curcumin indicated that some induced
the down-regulation of beta-catenin, Ki-ras, cyclin D1, c-Myc, and ErbB-2 at as
low as one eighth the concentration at which curcumin normally has an effect. The
analogues, however, exhibited neither harmful nor growth-suppressive effects on
normal hepatocytes where oncogene products are not activated. They also exhibited
no toxicities in vivo that they may provide effective alternative therapies for
the prevention and treatment of some human cancers.
PMID- 17041102
TI - Correction for chromosome-17 is critical for the determination of true Her-2/neu
gene amplification status in breast cancer.
AB - PURPOSE: Trastuzumab is the cornerstone for treatment of women with HER2
overexpressing breast cancer, both in the adjuvant and in the metastatic
settings. The accurate assessment of HER2 is, therefore, critical to identifying
patients who may benefit from trastuzumab-based therapy. This project aimed to
determine the optimal scoring method for fluorescence in situ hybridization
(FISH) assay. METHODS: FISH assay was done on 893 samples of breast cancer. Three
scoring methods were evaluated: Her2/CEP17> or =2, Her2>4, or Her2>6. Protein and
gene expression were evaluated by immunohistochemistry (n = 584) and
mRNA/assay/nucleic acid sequence-based amplification (NASBA; n = 90). RESULTS:
Samples were divided into five groups based on FISH results: disomic amplified
and nonamplified, polysomic amplified, nonamplified, and discordant (10.8% of
cases, mostly positive with Her2>4 scoring, but negative with the others).
Her2/CEP17> or =2 and Her2>6 scoring methods showed the best association (a) with
regard to FISH scoring (kappa = 0.906, P < 10(-6)) and (b) between FISH and
immunohistochemistry (3+ as positive; kappa > 0.650, P < 10(-6)) or NASBA (kappa
> 0.536, P < 10(-6)). Polysomy had an effect on Her2 copy number (P < 10(-6)),
but had no effect on protein and mRNA content. Therefore, within the discordant
subgroup, for which additive Her-2 gene copies are due to high polysomy, protein
and mRNA levels were similar to those of the nonamplified samples. For this
subgroup, the best concordance between FISH/immunohistochemistry/NASBA was
observed with the Her2/CEP17 ratio and Her-2>6 scoring (68% and 58% perfect
matches, respectively). No perfect matches were observed using the Her2>4 scoring
method. CONCLUSION: Correction for chromosome-17 is the method of choice for
clinical practice; Her-2>6, but not Her-2>4, could be used as an alternative.
PMID- 17041103
TI - Induction of apoptosis by monastrol, an inhibitor of the mitotic kinesin Eg5, is
independent of the spindle checkpoint.
AB - Spindle poisons such as paclitaxel are widely used as cancer therapeutics. By
interfering with microtubule dynamics, paclitaxel induces mitotic arrest and
apoptosis. Targeting the kinesin Eg5, which is required for the formation of a
bipolar spindle, is a promising therapeutic alternative to drugs that interfere
with microtubule dynamics. Recent data suggest that the spindle checkpoint can
determine the response of tumor cells to microtubule poisons. The relationship
between checkpoint function and Eg5 inhibition, however, has not yet been fully
investigated. Here, we used time-lapse video microscopy and biochemical analysis
to study the effect of spindle checkpoint abrogation on the response of HeLa
cells to monastrol, a selective Eg5 inhibitor. In HeLa cells, monastrol activated
the spindle checkpoint, leading to mitotic arrest and apoptosis. Small
interfering RNA-mediated depletion of the spindle checkpoint proteins BubR1 or
Mad2 significantly shortened drug-induced arrest, causing premature mitotic exit
without cell division. Time-lapse microscopy as well as analysis of caspase
activation shows that these checkpoint-deficient cells initiate apoptosis after
mitotic exit in response to monastrol. Checkpoint-deficient cells treated with
paclitaxel, on the other hand, yielded a higher frequency of cells with >4N DNA
content and a decreased incidence of apoptotic events, particularly in Mad2
depleted cells. These results indicate that the immediate fate of postmitotic
cells is influenced by both the nature of the checkpoint defect and the type of
drug used. Furthermore, these results show that inactivation of the kinesin Eg5
can induce apoptosis in tumor cells in the absence of critical spindle checkpoint
components.
PMID- 17041105
TI - Coronary artery giant aneurysm with fistulas to the left ventricular
diverticulum.
PMID- 17041106
TI - Mycotic aneurysm complicating prosthetic valve endocarditis.
PMID- 17041104
TI - Sensitization of B16 tumor cells with a CXCR4 antagonist increases the efficacy
of immunotherapy for established lung metastases.
AB - Expression of the chemokine receptor CXCR4 by tumor cells promotes metastasis,
possibly by activating prosurvival signals that render cancer cells resistant to
immune attack. Inhibition of CXCR4 with a peptide antagonist, T22, blocks
metastatic implantation of CXCR4-transduced B16 (CXCR4-luc-B16) melanoma cells in
lung, but not the outgrowth of established metastases, raising the question of
how T22 can best be used in a clinical setting. Herein, whereas the treatment of
CXCR4-luc-B16 cells in vitro with the CXCR4 ligand CXCL12 did not reduce killing
induced by cisplatin or cyclophosphamide, CXCL12 markedly reduced Fas-dependent
killing by gp100-specific (pmel-1) CD8(+) T cells. T22 pretreatment restored
sensitivity of CXCR4-luc-B16 cells to pmel-1 killing, even in the presence of
CXCL12. Two immune-augmenting regimens were used in combination with T22 to treat
experimental lung metastases. First, low-dose cyclophosphamide treatment (100
mg/kg) on day 5 in combination with T22 (days 4-7) yielded a approximately 70%
reduction of B16 metastatic tumor burden in the lungs compared with
cyclophosphamide treatment alone (P < 0.001). Furthermore, whereas anti-CTL
antigen 4 (CTLA4) monoclonal antibody (mAb; or T22 treatment) alone had little
effect on established B16 metastases, pretreatment with T22 (in combination with
anti-CTLA4 mAb) resulted in a 50% reduction in lung tumor burden (P = 0.02).
Thus, in vitro, CXCR4 antagonism with T22 renders B16 cells susceptible to
killing by antigen-specific T cells. In vivo, T22 synergizes with
cyclophosphamide or anti-CTLA4 mAb in the treatment of established lung
metastases, suggesting a novel strategy for augmenting the efficacy of
immunotherapy.
PMID- 17041107
TI - Pathological changes in the coronary arteries in the acute coronary syndromes.
PMID- 17041108
TI - Live three dimensional echocardiography in evaluation of left ventricular to
right atrial shunt (Gerbode defect).
PMID- 17041109
TI - Stent angioplasty in aortic arch interruption.
PMID- 17041110
TI - Prolapsing left atrial myxoma causing severe pulmonary hypertension: dynamic
echocardiographic and magnetic resonance imaging.
PMID- 17041111
TI - Sign of the times.
PMID- 17041112
TI - Angiographic presentation of sinus of Valsalva aneurysm.
PMID- 17041113
TI - Endothelialisation of an autologous pericardial valve implanted in the aortic
position.
PMID- 17041114
TI - New insight into the tricuspid valve in Ebstein anomaly using three-dimensional
echocardiography.
PMID- 17041115
TI - Multislice cardiac computed tomographic images of anomalous origin of the left
circumflex artery from the right coronary sinus.
PMID- 17041116
TI - Carbomedics bi-leaflet aortic valve prosthesis: a sticky problem.
PMID- 17041117
TI - Focal femoral artery narrowing caused by suture mediated closure device.
PMID- 17041118
TI - Sneddon's syndrome: cardiac involvement detected by magnetic resonance imaging.
PMID- 17041119
TI - Severe hypothermia showing Osborn waves associated with transient atrial
fibrillation and ST segment depression.
PMID- 17041120
TI - Is heart rate variability a valid parameter to predict sudden death in patients
with Becker's muscular dystrophy?
PMID- 17041121
TI - Postural sway in patients with syncope and poor orthostatic tolerance.
PMID- 17041122
TI - Different effects of atenolol and nebivolol on coronary flow reserve.
PMID- 17041123
TI - Cardiac arrest after occlusion of anomalous origin of left main artery.
PMID- 17041124
TI - Epidemiology and antibiotic treatment of infective endocarditis: an update.
PMID- 17041125
TI - Childhood risk factors for adult cardiovascular disease and primary prevention in
childhood.
PMID- 17041126
TI - Treating patients with ventricular ectopic beats.
PMID- 17041127
TI - Value of the sagittal abdominal diameter in coronary heart disease risk
assessment: cohort study in a large, multiethnic population.
AB - Whether visceral obesity predicts coronary heart disease (CHD) risk above and
beyond overall fatness remains unsettled. Moreover, whether the association
between visceral obesity and CHD risk differs by sex, age, race, and overall
fatness is poorly understood. The authors conducted a cohort study among 101,765
adult members of Kaiser Permanente of Northern California who underwent
multiphasic health checkups between 1965 and 1970. After a median of 12 years and
adjustment for age, race, body mass index (BMI), educational level, smoking,
alcohol consumption, and hormone replacement therapy (in women), the upper
quartile of standing sagittal abdominal diameter, relative to the lowest
quartile, was associated with a 1.42-fold increased hazard of CHD in men (95%
confidence interval: 1.30, 1.55) and a 1.44-fold increased hazard of CHD in women
(95% confidence interval: 1.30, 1.59). Further adjustment for metabolic mediators
attenuated the association minimally. Standing sagittal abdominal diameter was a
consistent predictor of CHD across racial groups but was more strongly associated
with CHD in the younger age group. Joint consideration of BMI/standing sagittal
abdominal diameter categories better discriminated risk of CHD compared with use
of BMI alone. In conclusion, standing sagittal abdominal diameter was a strong
predictor of CHD independently of BMI and added incremental CHD risk prediction
at each level of BMI.
PMID- 17041128
TI - Inaccessible novel questionnaires in published medical research: hidden methods,
hidden costs.
AB - Although critical analysis of survey research is limited when reviewers and
readers cannot view a study's questionnaire, access to novel questionnaires used
in published research has not been systematically examined. The authors
identified publications reporting the results of novel questionnaires in three
medical journals (JAMA, The New England Journal of Medicine, and The Lancet) in
January 2000-May 2003 and searched portable document format (PDF) versions of the
studies for the complete questionnaire or a Uniform Resource Locator (URL)
providing access to the questionnaire. When the questionnaire was not provided in
the publication or a published URL, the authors requested it from the
corresponding author in writing up to three times over a 6-week period. Of 93
publications with novel questionnaires, four printed the questionnaire in the
article and three provided online access. Corresponding authors failed to provide
questionnaires for 37 of 81 (46%) studies. Novel questionnaires used in published
research are frequently not available to readers or researchers. Policies that
improve access to novel questionnaires will allow better assessment of study
results, reduce duplicated efforts, and improve authorship attribution for
questionnaire design.
PMID- 17041129
TI - Height and body mass index and risk of lymphohematopoietic malignancies in two
million Norwegian men and women.
AB - Reports on the association between obesity and lymphohematopoietic malignancies
(LHMs) have been inconsistent. The present study aimed at exploring this
association for specific disease lymphohematopoietic entities in a large
Norwegian cohort. Height and weight were measured in two million Norwegian men
and women aged 20-74 years during 1963-2001. During follow-up, 24,500 cases of
LHMs were observed. Relative risks of disease were estimated by Cox proportional
hazards regression. The risk of LHMs overall increased moderately by increasing
body mass index and height in both sexes. The relative risk of LHMs per five-unit
increase in body mass index was 1.11 (95% confidence interval (CI): 1.08, 1.14)
in men and 1.08 (95% CI: 1.05, 1.11) in women. For each 10-cm increase in height,
the relative risk was 1.19 (95% CI: 1.16, 1.22) in men and 1.16 (95% CI: 1.12,
1.20) in women. Separate analyses for different lymphohematopoietic malignancies
did not reveal any group's being particularly strongly associated with body mass
index. A modest increase in the risk of LHMs combined was observed with
increasing height. The moderate associations between height and body mass index
and LHMs found in the present study indicate that the observed increase in
overweight/obesity plays only a minor role in explaining the increase in the
incidence of LHMs.
PMID- 17041130
TI - Re: "confounding of the relation between homocysteine and peripheral arterial
disease by lead, cadmium, and renal function".
PMID- 17041131
TI - Spouse resemblance in body mass index: effects on adult obesity prevalence in the
offspring generation.
AB - Accruing evidence indicates that mate selection is promoted by similarity in body
fatness. Assortative mating for obesity may contribute genetically to the obesity
epidemic by increasing the risk in subsequent generations. To test this
hypothesis, the authors analyzed measured and validated questionnaire data on
family members, obtained between 1987 and 2000 from 7,834 obese probands and from
829 subjects randomly ascertained from the general Swedish population. Spouse
correlations in body mass index were strongest among couples with the shortest
duration of cohabitation. Obesity concordance in parents was associated with an
obesity prevalence of 20.1% in adult offspring compared with 1.4% if parents were
concordantly nonobese (odds ratio = 18.3, 95% confidence interval: 9.0, 37.4).
The prevalence was 8.2% if parents were obesity discordant (odds ratio = 6.5, 95%
confidence interval: 3.2, 13.2). No association was found between rearing
parents' and nonbiologic offspring's body mass index. These results agree with
the hypothesis that assortative mating for obesity confers a higher risk of
obesity in the offspring generation and thus contributes to the obesity epidemic.
Parental obesity concordance is a strong, easily identifiable genetic risk factor
that should be considered in the complex network of risk factors for obesity in
designing primary prevention programs.
PMID- 17041132
TI - An internet-based method of selecting control populations for epidemiologic
studies.
AB - Identifying control subjects for epidemiologic studies continues to increase in
difficulty because of changes in telephone technology such as answering services
and machines, caller identification, and cell phones. An Internet-based method
for obtaining study subjects that may increase response rates has been developed
and is described. This method uses information from two websites that, when
combined, provide accurate and complete lists of names, addresses, and listed
phone numbers. This method was developed by use of randomly selected streets in a
suburb of Salt Lake City, Utah, in June 2005.
PMID- 17041133
TI - Invited commentary: the art of making questionnaires better.
AB - A paper by Schilling et al. (Am J Epidemiol 2006;164:1141-4) addresses a crucial
issue for epidemiologists: limited peer access to questionnaires. This limited
access hampers the ability to evaluate and improve the questions used by
investigators and, in turn, the quality of some of the self-reported data. The
authors of this commentary analyzed recent publications in core epidemiology
journals, finding that self-reported data were used in 64% of articles, but key
questions were seldom printed in the article (9%), and open access to complete
questionnaires (16%) was rarely provided. Only 47% of articles even discussed
validation; of these, only 67% actually validated questions used in the study.
The authors join Schilling et al. in making recommendations to improve
questionnaire access and collaboration. A first step, proposed before, involves
investigators posting their questionnaires on a website concurrently with
publication of their article. Journal editors should require online access to
full questionnaires for published articles and inclusion of key questions within
the article when possible. Funding agencies should take the lead in increasing
access and collaboration by developing a searchable database.
PMID- 17041134
TI - Childhood socioeconomic position and cause-specific mortality in early adulthood.
AB - There is growing evidence that childhood socioeconomic position (SEP) influences
adult health. The authors' aim was to describe the association between childhood
SEP measures (parents' education, occupation, and income) and mortality, for both
genders, and to assess to what extent this association was mediated by adult SEP.
Registry data for all Norwegians born in 1955-1965 were used. Death records were
linked to the cohort, and 6,589 persons died during 1990-2001. Cox's regression
was used to calculate relative rates and the relative index of inequality. Low
childhood SEP was associated with increased mortality for most causes of death,
except for breast cancer, where no association was found. For suicide in women,
low childhood SEP was protective. Adult SEP accounted for the associations for
total mortality and most causes of death. However, adult SEP accounted for only
one half of the association of father's educational level with ischemic heart
disease mortality among men. The increased suicide risk among women with high
childhood SEP persisted, regardless of adult SEP. In summary, childhood SEP had a
direct association with early adult cardiovascular mortality in men and with
suicide in women. For other causes of death, childhood SEP was only indirectly
associated, mostly through persons' own educational level.
PMID- 17041135
TI - Associations between findings on cranial magnetic resonance imaging and retinal
photography in the elderly: the Cardiovascular Health Study.
AB - Associations between findings on cranial magnetic resonance imaging (MRI) and
retinal photographs have been described mostly in middle-aged people. In the
Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal
photography between 1991 and 1999. Associations were sought between MRI findings
and four findings of retinal microvascular disease: retinopathy, focal arteriolar
narrowing, arteriovenous nicking, and the arteriovenous ratio--the last based
upon semiautomated measurements of arterioles and venules. After controlling for
age and gender, the authors found associations between MRI findings and the
smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts
(odds ratio = 1.18, 95% confidence interval: 1.05, 1.34; p = 0.007), white matter
grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio =
1.26, 95% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter
grade (odds ratio = 1.12, 95% confidence interval: 0.98, 1.29; p = 0.09).
Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95%
confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95%
confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension
and diabetes had minimal effect. Evidence of small vessel disease in the retina
increases the likelihood of finding it in the brain. Associations were less
prominent in this elderly population than have been described in middle-aged
people.
PMID- 17041136
TI - Helicobacter pylori persistence: an overview of interactions between H. pylori
and host immune defenses.
AB - Helicobacter pylori is a gram-negative bacterium that persistently colonizes more
than half of the global human population. In order to successfully colonize the
human stomach, H. pylori must initially overcome multiple innate host defenses.
Remarkably, H. pylori can persistently colonize the stomach for decades or an
entire lifetime despite development of an acquired immune response. This review
focuses on the immune response to H. pylori and the mechanisms by which H. pylori
resists immune clearance. Three main sections of the review are devoted to (i)
analysis of the immune response to H. pylori in humans, (ii) analysis of
interactions of H. pylori with host immune defenses in animal models, and (iii)
interactions of H. pylori with immune cells in vitro. The topics addressed in
this review are important for understanding how H. pylori resists immune
clearance and also are relevant for understanding the pathogenesis of diseases
caused by H. pylori (peptic ulcer disease, gastric adenocarcinoma, and gastric
lymphoma).
PMID- 17041137
TI - Emerging respiratory viruses: challenges and vaccine strategies.
AB - The current threat of avian influenza to the human population, the potential for
the reemergence of severe acute respiratory syndrome (SARS)-associated
coronavirus, and the identification of multiple novel respiratory viruses
underline the necessity for the development of therapeutic and preventive
strategies to combat viral infection. Vaccine development is a key component in
the prevention of widespread viral infection and in the reduction of morbidity
and mortality associated with many viral infections. In this review we describe
the different approaches currently being evaluated in the development of vaccines
against SARS-associated coronavirus and avian influenza viruses and also
highlight the many obstacles encountered in the development of these vaccines.
Lessons learned from current vaccine studies, coupled with our increasing
knowledge of the host and viral factors involved in viral pathogenesis, will help
to increase the speed with which efficacious vaccines targeting newly emerging
viral pathogens can be developed.
PMID- 17041138
TI - Ventilator-associated pneumonia: diagnosis, treatment, and prevention.
AB - While critically ill patients experience a life-threatening illness, they
commonly contract ventilator-associated pneumonia. This nosocomial infection
increases morbidity and likely mortality as well as the cost of health care. This
article reviews the literature with regard to diagnosis, treatment, and
prevention. It provides conclusions that can be implemented in practice as well
as an algorithm for the bedside clinician and also focuses on the controversies
with regard to diagnostic tools and approaches, treatment plans, and prevention
strategies.
PMID- 17041140
TI - Developmental biology of sporozoite-host interactions in Plasmodium falciparum
malaria: implications for vaccine design.
AB - The Plasmodium falciparum sporozoite infects different types of cells in a
mosquito's salivary glands and human epithelial and Kuppfer cells and
hepatocytes. These become differentiated later on, transforming themselves into
the invasive red blood cell form, the merozoite. The ability of sporozoites to
interact with different types of cells requires a wide variety of mechanisms
allowing them to survive in both hosts: mobility, receptor-ligand interactions
with different cellular receptors, and transformation and development into other
invasive parasite forms, which are vitally important for parasite survival.
Sporozoite complexity is reflected in the large quantity of proteins that can be
expressed. Some of them have been extensively studied, such as CSP, TRAP, STARP,
LSA-1, LSA-3, SALSA, SPECT1, SPECT2, MAEBL, and SPATR, due to their importance in
infection and their potential use as vaccines. Our work has been focused on the
search for the molecular mechanisms of parasite-host cellular receptor-ligand
interactions by identifying amino acid sequences and the critical binding
residues from these proteins relevant to parasite invasion. Once such sequences
have been identified, it will be possible to modify them to induce a strong
immune response against P. falciparum in the experimental Aotus monkey model.
This all leads towards developing multistage, multicomponent, subunit-based
vaccines that will be effective in eradicating or controlling malaria caused by
P. falciparum.
PMID- 17041139
TI - Molecular epidemiology of tuberculosis: current insights.
AB - Molecular epidemiologic studies of tuberculosis (TB) have focused largely on
utilizing molecular techniques to address short- and long-term epidemiologic
questions, such as in outbreak investigations and in assessing the global
dissemination of strains, respectively. This is done primarily by examining the
extent of genetic diversity of clinical strains of Mycobacterium tuberculosis.
When molecular methods are used in conjunction with classical epidemiology, their
utility for TB control has been realized. For instance, molecular epidemiologic
studies have added much-needed accuracy and precision in describing transmission
dynamics, and they have facilitated investigation of previously unresolved
issues, such as estimates of recent-versus-reactive disease and the extent of
exogenous reinfection. In addition, there is mounting evidence to suggest that
specific strains of M. tuberculosis belonging to discrete phylogenetic clusters
(lineages) may differ in virulence, pathogenesis, and epidemiologic
characteristics, all of which may significantly impact TB control and vaccine
development strategies. Here, we review the current methods, concepts, and
applications of molecular approaches used to better understand the epidemiology
of TB.
PMID- 17041141
TI - Coinfections acquired from ixodes ticks.
AB - The pathogens that cause Lyme disease (LD), human anaplasmosis, and babesiosis
can coexist in Ixodes ticks and cause human coinfections. Although the risk of
human coinfection differs by geographic location, the true prevalence of
coinfecting pathogens among Ixodes ticks remains largely unknown for the majority
of geographic locations. The prevalence of dually infected Ixodes ticks appears
highest among ticks from regions of North America and Europe where LD is endemic,
with reported prevalences of < or =28%. In North America and Europe, the majority
of tick-borne coinfections occur among humans with diagnosed LD. Humans
coinfected with LD and babesiosis appear to have more intense, prolonged symptoms
than those with LD alone. Coinfected persons can also manifest diverse, influenza
like symptoms, and abnormal laboratory test results are frequently observed.
Coinfecting pathogens might alter the efficiency of transmission, cause
cooperative or competitive pathogen interactions, and alter disease severity
among hosts. No prospective studies to assess the immunologic effects of
coinfection among humans have been conducted, but animal models demonstrate that
certain coinfections can modulate the immune response. Clinicians should consider
the likelihood of coinfection when pursuing laboratory testing or selecting
therapy for patients with tick-borne illness.
PMID- 17041142
TI - Going wild: lessons from naturally occurring T-lymphotropic lentiviruses.
AB - Over 40 nonhuman primate (NHP) species harbor species-specific simian
immunodeficiency viruses (SIVs). Similarly, more than 20 species of nondomestic
felids and African hyenids demonstrate seroreactivity against feline
immunodeficiency virus (FIV) antigens. While it has been challenging to study the
biological implications of nonfatal infections in natural populations,
epidemiologic and clinical studies performed thus far have only rarely detected
increased morbidity or impaired fecundity/survival of naturally infected SIV- or
FIV-seropositive versus -seronegative animals. Cross-species transmissions of
these agents are rare in nature but have been used to develop experimental
systems to evaluate mechanisms of pathogenicity and to develop animal models of
HIV/AIDS. Given that felids and primates are substantially evolutionarily removed
yet demonstrate the same pattern of apparently nonpathogenic lentiviral
infections, comparison of the biological behaviors of these viruses can yield
important implications for host-lentiviral adaptation which are relevant to human
HIV/AIDS infection. This review therefore evaluates similarities in epidemiology,
lentiviral genotyping, pathogenicity, host immune responses, and cross-species
transmission of FIVs and factors associated with the establishment of lentiviral
infections in new species. This comparison of consistent patterns in lentivirus
biology will expose new directions for scientific inquiry for understanding the
basis for virulence versus avirulence.
PMID- 17041145
TI - The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by
TLR ligands.
AB - The endogenous anti-microbial peptide LL-37/hCAP-18 is an effector molecule of
the innate host defense system at surfaces of the body. Besides its direct anti
microbial activity, the peptide interacts with different cell types. Dendritic
cells (DCs) play a central role in mucosal host defense. It was the aim of the
study to determine whether LL-37 modulates the response of DCs to pathogen
associated molecular patterns. Monocyte-derived DCs were stimulated with the Toll
like receptors (TLRs) ligands LPS, lipoteichoic acid and flagellin. We measured
classical markers of DC maturation and assayed the ability of the DCs to activate
T cell responses. Co-incubation with LL-37 resulted in suppressed activation of
DCs. Levels of released IL-6, IL-12p70 and TNF-alpha and surface expression of
HLA-DR, CD80, CD83, CD86 and the chemokine receptor CCR7 were decreased. Exposure
of DCs to LL-37 during LPS exposure induced co-cultured naive T cells to produce
less IL-2 and IFN-gamma and decreased their proliferation. The response of memory
T cells to a recall antigen was also decreased. In conclusion, we demonstrate
that the anti-microbial peptide LL-37 inhibits the activation of DCs by TLR
ligands. We propose that LL-37 is a regulator of host defense responses at the
intersection of innate and adaptive immune systems.
PMID- 17041143
TI - Human pharmacogenomic variations and their implications for antifungal efficacy.
AB - Pharmacogenomics is defined as the study of the impacts of heritable traits on
pharmacology and toxicology. Candidate genes with potential pharmacogenomic
importance include drug transporters involved in absorption and excretion, phase
I enzymes (e.g., cytochrome P450-dependent mixed-function oxidases) and phase II
enzymes (e.g., glucuronosyltransferases) contributing to metabolism, and those
molecules (e.g., albumin, A1-acid glycoprotein, and lipoproteins) involved in the
distribution of antifungal compounds. By using the tools of population genetics
to define interindividual differences in drug absorption, distribution,
metabolism, and excretion, pharmacogenomic models for genetic variations in
antifungal pharmacokinetics can be derived. Pharmacogenomic factors may become
especially important in the treatment of immunocompromised patients or those with
persistent or refractory mycoses that cannot be explained by elevated MICs and
where rational dosage optimization of the antifungal agent may be particularly
critical. Pharmacogenomics has the potential to shift the paradigm of therapy and
to improve the selection of antifungal compounds and adjustment of dosage based
upon individual variations in drug absorption, metabolism, and excretion.
PMID- 17041144
TI - Updated review of blood culture contamination.
AB - Blood culture contamination represents an ongoing source of frustration for
clinicians and microbiologists alike. Ambiguous culture results often lead to
diagnostic uncertainty in clinical management and are associated with increased
health care costs due to unnecessary treatment and testing. A variety of
strategies have been investigated and employed to decrease contamination rates.
In addition, numerous approaches to increase our ability to distinguish between
clinically significant bacteremia and contamination have been explored. In recent
years, there has been an increase in the application of computer-based tools to
support infection control activities as well as provide clinical decision support
related to the management of infectious diseases. Finally, new approaches for
estimating bacteremia risk which have the potential to decrease unnecessary blood
culture utilization have been developed and evaluated. In this review, we provide
an overview of blood culture contamination and describe the potential utility of
a variety of approaches to improve both detection and prevention. While it is
clear that progress is being made, fundamental challenges remain.
PMID- 17041146
TI - A p67Phox-like regulator is recruited to control hyphal branching in a fungal
grass mutualistic symbiosis.
AB - Key requirements for microbes to initiate and establish mutualistic symbiotic
interactions with plants are evasion of potential host defense responses and
strict control of microbial growth. Reactive oxygen species (ROS) produced by a
specific NADPH oxidase isoform, NoxA, regulate hyphal growth in the mutualistic
interaction between the fungal endophyte Epichloe festucae and its grass host
Lolium perenne. Unlike mammalian systems, little is known about the fungal NADPH
oxidase complex and its response to differentiation signals. We identify an E.
festucae p67(phox)-like regulator, NoxR, dispensable in culture but essential in
planta for the symbiotic interaction. Plants infected with a noxR deletion mutant
show severe stunting and premature senescence, whereas hyphae in the meristematic
tissues show increased branching leading to increased fungal colonization of
pseudostem and leaf blade tissue. Inhibition of ROS production or overexpression
of noxR recapitulates the hyperbranching phenotype in culture. NoxR interacts in
vitro with the small GTP binding protein RacA and requires a functional RacA
binding site to complement the noxR mutant and restore the wild-type plant
interaction phenotype. These results show that NoxR is a key regulator of NoxA in
symbiosis, where it acts together with RacA to spatially regulate ROS production
and control hyphal branching and patterning.
PMID- 17041147
TI - A pentatricopeptide repeat protein facilitates the trans-splicing of the maize
chloroplast rps12 pre-mRNA.
AB - The pentatricopeptide repeat (PPR) is a degenerate 35-amino acid repeat motif
that is widely distributed among eukaryotes. Genetic, biochemical, and
bioinformatic data suggest that many PPR proteins influence specific
posttranscriptional steps in mitochondrial or chloroplast gene expression and
that they may typically bind RNA. However, biological functions have been
determined for only a few PPR proteins, and with few exceptions, substrate RNAs
are unknown. To gain insight into the functions and substrates of the PPR protein
family, we characterized the maize (Zea mays) nuclear gene ppr4, which encodes a
chloroplast-targeted protein harboring both a PPR tract and an RNA recognition
motif. Microarray analysis of RNA that coimmunoprecipitates with PPR4 showed that
PPR4 is associated in vivo with the first intron of the plastid rps12 pre-mRNA, a
group II intron that is transcribed in segments and spliced in trans. ppr4
mutants were recovered through a reverse-genetic screen and shown to be defective
for rps12 trans-splicing. The observations that PPR4 is associated in vivo with
rps12-intron 1 and that it is also required for its splicing demonstrate that
PPR4 is an rps12 trans-splicing factor. These findings add trans-splicing to the
list of RNA-related functions associated with PPR proteins and suggest that
plastid group II trans-splicing is performed by different machineries in vascular
plants and algae.
PMID- 17041148
TI - A rice Tc1/mariner-like element transposes in yeast.
AB - The Tc1/mariner transposable element superfamily is widely distributed in animal
and plant genomes. However, no active plant element has been previously
identified. Nearly identical copies of a rice (Oryza sativa) Tc1/mariner element
called Osmar5 in the genome suggested potential activity. Previous studies
revealed that Osmar5 encoded a protein that bound specifically to its own ends.
In this report, we show that Osmar5 is an active transposable element by
demonstrating that expression of its coding sequence in yeast promotes the
excision of a nonautonomous Osmar5 element located in a reporter construct.
Element excision produces transposon footprints, whereas element reinsertion
occurs at TA dinucleotides that were either tightly linked or unlinked to the
excision site. Several site-directed mutations in the transposase abolished
activity, whereas mutations in the transposase binding site prevented
transposition of the nonautonomous element from the reporter construct. This
report of an active plant Tc1/mariner in yeast will provide a foundation for
future comparative analyses of animal and plant elements in addition to making a
new wide host range transposable element available for plant gene tagging.
PMID- 17041149
TI - Retention of a bean phaseolin/maize gamma-Zein fusion in the endoplasmic
reticulum depends on disulfide bond formation.
AB - Most seed storage proteins of the prolamin class accumulate in the endoplasmic
reticulum (ER) as large insoluble polymers termed protein bodies (PBs), through
mechanisms that are still poorly understood. We previously showed that a fusion
between the Phaseolus vulgaris vacuolar storage protein phaseolin and the N
terminal half of the Zea mays prolamin gamma-zein forms ER-located PBs. Zeolin
has 6 Cys residues and, like gamma-zein with 15 residues, is insoluble unless
reduced. The contribution of disulfide bonds to zeolin destiny was determined by
studying in vivo the effects of 2-mercaptoethanol (2-ME) and by zeolin
mutagenesis. We show that in tobacco (Nicotiana tabacum) protoplasts, 2-ME
enhances interactions of newly synthesized proteins with the ER chaperone BiP and
inhibits the secretory traffic of soluble proteins with or without disulfide
bonds. In spite of this general inhibition, 2-ME enhances the solubility of
zeolin and relieves its retention in the ER, resulting in increased zeolin
traffic. Consistently, mutated zeolin unable to form disulfide bonds is soluble
and efficiently enters the secretory traffic without 2-ME treatment. We conclude
that disulfide bonds that lead to insolubilization are a determinant for PB
mediated protein accumulation in the ER.
PMID- 17041151
TI - Comparative genome analysis of the neurexin gene family in Danio rerio: insights
into their functions and evolution.
AB - Neurexins constitute a family of proteins originally identified as synaptic
transmembrane receptors for a spider venom toxin. In mammals, the 3 known
Neurexin genes present 2 alternative promoters that drive the synthesis of a long
(alpha) and a short (beta) form and contain different sites of alternative
splicing (AS) that can give rise to thousands of different transcripts. To date,
very little is known about the significance of this variability, except for the
modulation of binding to some of the Neurexin ligands. Although orthologs of
Neurexins have been isolated in invertebrates, these genes have been studied
mostly in mammals. With the aim of investigating their functions in lower
vertebrates, we chose Danio rerio as a model because of its increasing importance
in comparative biology. We have isolated 6 zebrafish homologous genes, which are
highly conserved at the structural level and display a similar regulation of AS,
despite about 450 Myr separating the human and zebrafish species. Our data
indicate a strong selective pressure at the exonic level and on the intronic
borders, in particular on the regulative intronic sequences that flank the exons
subject to AS. Such a selective pressure could help conserve the regulation and
consequently the function of these genes along the vertebrates evolutive tree. AS
analysis during development shows that all genes are expressed and finely
regulated since the earliest stages of development, but mark an increase after
the 24-h stage that corresponds to the beginning of synaptogenesis. Moreover, we
found that specific isoforms of a zebrafish Neurexin gene (nrxn1a) are expressed
in the adult testis and in the earliest stages of development, before the
beginning of zygotic transcription, indicating a potential delivery of paternal
RNA to the embryo. Our analysis suggests the existence of possible new functions
for Neurexins, serving as the basis for novel approaches to the functional
studies of this complex neuronal protein family and more in general to the
understanding of the AS mechanism in low vertebrates.
PMID- 17041150
TI - Abiotic stress generates ROS that signal expression of anionic glutamate
dehydrogenases to form glutamate for proline synthesis in tobacco and grapevine.
AB - Glutamate dehydrogenase (GDH) may be a stress-responsive enzyme, as GDH exhibits
considerable thermal stability, and de novo synthesis of the alpha-GDH subunit is
induced by exogenous ammonium and senescence. NaCl treatment induces reactive
oxygen species (ROS), intracellular ammonia, expression of tobacco (Nicotiana
tabacum cv Xanthi) gdh-NAD;A1 encoding the alpha-subunit of GDH, increase in
immunoreactive alpha-polypeptide, assembly of the anionic isoenzymes, and in
vitro GDH aminating activity in tissues from hypergeous plant organs. In vivo
aminating GDH activity was confirmed by gas chromatorgraphy-mass spectrometry
monitoring of (15)N-Glu, (15)N-Gln, and (15)N-Pro in the presence of methionine
sulfoximine and amino oxyacetic acid, inhibitors of Gln synthetase and
transaminases, respectively. Along with upregulation of alpha-GDH by NaCl,
isocitrate dehydrogenase genes, which provide 2-oxoglutarate, are also induced.
Treatment with menadione also elicits a severalfold increase in ROS and
immunoreactive alpha-polypeptide and GDH activity. This suggests that ROS
participate in the signaling pathway for GDH expression and protease activation,
which contribute to intracellular hyperammonia. Ammonium ions also mimic the
effects of salinity in induction of gdh-NAD;A1 expression. These results,
confirmed in tobacco and grape (Vitis vinifera cv Sultanina) tissues, support the
hypothesis that the salinity-generated ROS signal induces alpha-GDH subunit
expression, and the anionic iso-GDHs assimilate ammonia, acting as antistress
enzymes in ammonia detoxification and production of Glu for Pro synthesis.
PMID- 17041152
TI - Maximum likelihood estimation of ancestral codon usage bias parameters in
Drosophila.
AB - We present a likelihood method for estimating codon usage bias parameters along
the lineages of a phylogeny. The method is an extension of the classical codon
based models used for estimating dN/dS ratios along the lineages of a phylogeny.
However, we add one extra parameter for each lineage: the selection coefficient
for optimal codon usage (S), allowing joint maximum likelihood estimation of S
and the dN/dS ratio. We apply the method to previously published data from
Drosophila melanogaster, Drosophila simulans, and Drosophila yakuba and show, in
accordance with previous results, that the D. melanogaster lineage has
experienced a reduction in the selection for optimal codon usage. However, the D.
melanogaster lineage has also experienced a change in the biological mutation
rates relative to D. simulans, in particular, a relative reduction in the
mutation rate from A to G and an increase in the mutation rate from C to T.
However, neither a reduction in the strength of selection nor a change in the
mutational pattern can alone explain all of the data observed in the D.
melanogaster lineage. For example, we also confirm previous results showing that
the Notch locus has experienced positive selection for previously classified
unpreferred mutations.
PMID- 17041153
TI - Molecular architecture of the DNA-binding region and its relationship to
classification of basic helix-loop-helix proteins.
AB - Multivariate statistical analyses are used to explore the molecular architecture
of the DNA-binding and dimerization regions of basic helix-loop-helix (bHLH)
proteins. Alphabetic amino acid data are transformed to biologically meaningful
quantitative values using a set of 5 multivariate "indices." These multivariate
indices summarize variation in a large suite of amino acid physiochemical
attributes and reflect variability in polarity-accessibility-hydrophobicity,
propensity for secondary structure, molecular size, codon composition, and
electrostatic charge. Using these index score data, discriminant analyses
describe the multidimensional aspects of physiochemical variation and clarify the
structural basis of the prevailing evolutionary classification of bHLH proteins.
A small number of amino acids from both the binding dimerization domains, when
considered simultaneously, accurately distinguish the 5 known DNA-binding groups.
The relevant sites often have well-documented structural and functional
characteristics.
PMID- 17041154
TI - Genetic manipulation of Prochlorococcus strain MIT9313: green fluorescent protein
expression from an RSF1010 plasmid and Tn5 transposition.
AB - Prochlorococcus is the smallest oxygenic phototroph yet described. It numerically
dominates the phytoplankton community in the mid-latitude oceanic gyres, where it
has an important role in the global carbon cycle. The complete genomes of several
Prochlorococcus strains have been sequenced, revealing that nearly half of the
genes in each genome are of unknown function. Genetic methods, such as reporter
gene assays and tagged mutagenesis, are critical to unveiling the functions of
these genes. Here, we describe conditions for the transfer of plasmid DNA into
Prochlorococcus strain MIT9313 by interspecific conjugation with Escherichia
coli. Following conjugation, E. coli bacteria were removed from the
Prochlorococcus cultures by infection with E. coli phage T7. We applied these
methods to show that an RSF1010-derived plasmid will replicate in Prochlorococcus
strain MIT9313. When this plasmid was modified to contain green fluorescent
protein, we detected its expression in Prochlorococcus by Western blotting and
cellular fluorescence. Further, we applied these conjugation methods to show that
a mini-Tn5 transposon will transpose in vivo in Prochlorococcus. These genetic
advances provide a basis for future genetic studies with Prochlorococcus, a
microbe of ecological importance in the world's oceans.
PMID- 17041155
TI - Virus-specific responses of Heterosigma akashiwo to infection.
AB - We used flow cytometry to examine the process of cell death in the bloom-forming
alga Heterosigma akashiwo during infection by a double-stranded DNA virus (OIs1)
and a single-stranded RNA virus (H. akashiwo RNA virus [HaRNAV]). These viruses
were isolated from the same geographic area and infect the same strain of H.
akashiwo. By use of the live/dead stains fluorescein diacetate and SYTOX green as
indicators of cellular physiology, cells infected with OIs1 showed signs of
infection earlier than HaRNAV-infected cultures (6 to 17 h versus 23 to 29 h).
Intracellular esterase activity was lost prior to increased membrane permeability
during infection with OIs1, while the opposite was seen with HaRNAV-infected
cultures. In addition, OIs1-infected cells accumulated in the cultures while
HaRNAV-infected cells rapidly disintegrated. Progeny OIs1 viruses consisted of
large and small morphotypes with estimated latent periods of 11 and 17 h,
respectively, and about 1,100 and 16,000 viruses produced per cell, respectively.
In contrast, HaRNAV produced about 21,000 viruses per cell and had a latent
period of 29 h. This study reveals that the characteristics of viral infection in
algae are virus dependent and therefore are variable among viruses infecting the
same species. This is an important consideration for ecosystem modeling
exercises; calculations based on in situ measurements of algal physiology must be
sensitive to the diverse responses of algae to viral infection.
PMID- 17041156
TI - Bestowing inducibility on the cloned methanol dehydrogenase promoter (PmxaF) of
Methylobacterium extorquens by applying regulatory elements of Pseudomonas putida
F1.
AB - PmxaF is a strong methanol-inducible promoter in Methylobacterium extorquens.
When this promoter is cloned in expression vectors and used to drive heterologous
gene expression, methanol inducibility is either greatly reduced or entirely
lost. In order to bestow inducibility upon the cloned PmxaF promoter in
expression vectors, we adopted combinational methods (regulatory elements of the
Pseudomonas putida F1 cym and cmt operons and Tn7 transposon system) to control
reporter gene expression at the transcriptional level in M. extorquens. An
operator fragment (26 nucleotides) of the cmt operon was inserted downstream of
the cloned PmxaF promoter in the broad-host-range expression vector (pCHOI3). The
repressor gene (cymR) located upstream of the cym operon in P. putida F1 was
amplified by PCR. To avoid cellular toxicity for M. extorquens caused by the
overexpression of CymR, single and/or double copies of cymR were integrated into
the chromosome of M. extorquens using the mini-Tn7 transposon system. Cultures
containing the chromosomally integrated cymR gene were subsequently transformed
with pCHOI3 containing modified PmxaF (i.e., PmxaF plus operator). In this
construct, inducibility is afforded by cumate (p-isopropylbenzoate). In this
report, we describe the inducible and tightly regulated expression of
heterologous genes (bgl [for beta-galactosidase], est [for esterase], and gfp
[for green fluorescent protein]) in M. extorquens. This is the first documented
example of an inducible/regulated heterologous gene expression system in M.
extorquens.
PMID- 17041157
TI - Study of biochemical pathways and enzymes involved in pyrene degradation by
Mycobacterium sp. strain KMS.
AB - Pyrene degradation is known in bacteria. In this study, Mycobacterium sp. strain
KMS was used to study the metabolites produced during, and enzymes involved in,
pyrene degradation. Several key metabolites, including pyrene-4,5-dione, cis-4,5
pyrene-dihydrodiol, phenanthrene-4,5-dicarboxylic acid, and 4-phenanthroic acid,
were identified during pyrene degradation. Pyrene-4,5-dione, which accumulates as
an end product in some gram-negative bacterial cultures, was further utilized and
degraded by Mycobacterium sp. strain KMS. Enzymes involved in pyrene degradation
by Mycobacterium sp. strain KMS were studied, using 2-D gel electrophoresis. The
first protein in the catabolic pathway, aromatic-ring-hydroxylating dioxygenase,
which oxidizes pyrene to cis-4,5-pyrene-dihydrodiol, was induced with the
addition of pyrene and pyrene-4,5-dione to the cultures. The subcomponents of
dioxygenase, including the alpha and beta subunits, 4Fe-4S ferredoxin, and the
Rieske (2Fe-2S) region, were all induced. Other proteins responsible for further
pyrene degradation, such as dihydrodiol dehydrogenase, oxidoreductase, and
epoxide hydrolase, were also found to be significantly induced by the presence of
pyrene and pyrene-4,5-dione. Several nonpathway-related proteins, including
sterol-binding protein and cytochrome P450, were induced. A pyrene degradation
pathway for Mycobacterium sp. strain KMS was proposed and confirmed by proteomic
study by identifying almost all the enzymes required during the initial steps of
pyrene degradation.
PMID- 17041158
TI - Sec-mediated transport of posttranslationally dehydrated peptides in Lactococcus
lactis.
AB - Nisin is a lanthionine-containing antimicrobial peptide produced by Lactococcus
lactis. Its (methyl)lanthionines are introduced by two posttranslational
enzymatic steps involving the dehydratase NisB, which dehydrates serine and
threonine residues, and the cyclase NisC, which couples these dehydrated residues
to cysteines, yielding thioether-bridged amino acids called lanthionines. The
prenisin is subsequently exported by the ABC transporter NisT and extracellularly
processed by the peptidase NisP. L. lactis expressing the nisBTC genes can modify
and secrete a wide range of nonlantibiotic peptides. Here we demonstrate that in
the absence of NisT and NisC, the Sec pathway of L. lactis can be exploited for
the secretion of dehydrated variants of therapeutic peptides. Furthermore,
posttranslational modifications by NisB and NisC still occur even when the nisin
leader is preceded by a Sec signal peptide or a Tat signal peptide 27 or 44 amino
acids long, respectively. However, transport of fully modified prenisin via the
Sec pathway is impaired. The extent of NisB-mediated dehydration could be
improved by raising the intracellular concentration NisB or by modulating the
export efficiency through altering the signal sequence. These data demonstrate
that besides the traditional lantibiotic transporter NisT, the Sec pathway with
an established broad substrate range can be utilized for the improved export of
lantibiotic enzyme-modified (poly)peptides.
PMID- 17041159
TI - Different levels of transcriptional regulation due to trophic constraints in the
reduced genome of Buchnera aphidicola APS.
AB - Symbiotic associations involving intracellular microorganisms and animals are
widespread, especially for species feeding on poor or unbalanced diets. Buchnera
aphidicola, the obligate intracellular bacterium associated with most aphid
species, provides its hosts with essential amino acids (EAAs), nutrients in short
supply in the plant phloem sap. The Buchnera genome has undergone severe
reductions during intracellular evolution. Genes for EAA biosynthesis are
conserved, but most of the transcriptional regulatory elements are lost. This
work addresses two main questions: is transcription in Buchnera (i) regulated and
(ii) scaled to aphid EAA demand? Two microarray experiments were designed for
profiling the gene expression in Buchnera. The first one was characterized by a
specific depletion of tyrosine and phenylalanine in the aphid diet, and the
second experiment combined a global diminution of EAAs in the aphid diet with a
sucrose concentration increase to manipulate the aphid growth rate. Aphid
biological performance and budget analysis (the balance between EAAs provided by
the diet and those synthesized by Buchnera) were performed to quantify the
nutritional demand from the aphids toward their symbiotic bacteria. Despite the
absence of known regulatory elements, a significant transcriptional regulation
was observed at different levels of organization in the Buchnera genome: between
genes, within putative transcription units, and within specific metabolic
pathways. However, unambiguous evidence for transcriptional changes underpinning
the scaling of EAA biosynthesis to aphid demand was not obtained. The phenotypic
relevance of the transcriptional response from the reduced genome of Buchnera is
addressed.
PMID- 17041160
TI - Antimicrobial use and resistance in swine waste treatment systems.
AB - Chlortetracycline and the macrolide tylosin were identified as commonly used
antimicrobials for growth promotion and prophylaxis in swine production.
Resistance to these antimicrobials was measured throughout the waste treatment
processes at five swine farms by culture-based and molecular methods.
Conventional farm samples had the highest levels of resistance with both culture
based and molecular methods and had similar levels of resistance despite
differences in antimicrobial usage. The levels of resistance in organic farm
samples, where no antimicrobials were used, were very low by a culture-based
method targeting fecal streptococci. However, when the same samples were analyzed
with a molecular method detecting methylation of a specific nucleotide in the 23S
rRNA that results in resistance to macrolides, lincosamides, and streptogramin B
(MLSB), an unexpectedly high level of resistant rRNA (approximately 50%) was
observed, suggesting that the fecal streptococci were not an appropriate target
group to evaluate resistance in the overall microbial community and that
background levels of MLSB resistance may be substantial. All of the feed samples
tested, including those from the organic farm, contained tetracycline resistance
genes. Generally, the same tetracycline resistance genes and frequency of
detection were found in the manure and lagoon samples for each commercial farm.
The levels of tetracycline and MLSB resistance remained high throughout the waste
treatment systems, suggesting that the potential impact of land application of
treated wastes and waste treatment by-products on environmental levels of
resistance should be investigated further.
PMID- 17041162
TI - Identification of human and animal adenoviruses and polyomaviruses for
determination of sources of fecal contamination in the environment.
AB - The Adenoviridae and Polyomaviridae families comprise a wide diversity of viruses
which may be excreted for long periods in feces or urine. In this study, a
preliminary analysis of the prevalence in the environment and the potential
usefulness as source-tracking tools of human and animal adenoviruses and
polyomaviruses has been developed. Molecular assays based on PCR specifically
targeting human adenoviruses (HAdV), porcine adenoviruses (PAdV), bovine
adenoviruses (BAdV), and bovine polyomaviruses (BPyV) were applied to
environmental samples including urban sewage, slaughterhouse, and river water
samples. PAdV and BPyV were detected in a very high percentage of samples
potentially affected by either porcine or bovine fecal contamination,
respectively. However, BAdV were detected in only one sample, showing a lower
prevalence than BPyV in the wastewater samples analyzed. The 22 slaughterhouse
samples with fecal contamination of animal origin showed negative results for the
presence of HAdV. The river water samples analyzed were positive for the presence
of both human and animal adenoviruses and polyomaviruses, indicating the
existence of diverse sources of contamination. The identities of the viruses
detected were confirmed by analyses of the amplified sequences. All BPyV isolates
showed a 97% similarity in nucleotide sequences. This is the first time that
PAdV5, BAdV6, and BPyV have been reported to occur in environmental samples.
Human and porcine adenoviruses and human and bovine polyomaviruses are proposed
as tools for evaluating the presence of viral contamination and for tracking the
origin of fecal/urine contamination in environmental samples.
PMID- 17041163
TI - Comparative effects of osmotic, sodium nitrite-induced, and pH-induced stress on
growth and survival of Clostridium perfringens type A isolates carrying
chromosomal or plasmid-borne enterotoxin genes.
AB - About 1 to 2% of Clostridium perfringens isolates carry the enterotoxin gene
(cpe) necessary for causing C. perfringens type A food poisoning. While the cpe
gene can be either chromosomal or plasmid borne, food poisoning isolates usually
carry a chromosomal cpe gene. Previous studies have linked this association
between chromosomal cpe isolates (i.e., C-cpe isolates) and food poisoning, at
least in part, to both the spores and vegetative cells of C-cpe isolates being
particularly resistant to high and low temperatures. The current study now
reveals that the resistance phenotype of C-cpe isolates extends beyond
temperature resistance to also include, for both vegetative cells and spores,
enhanced resistance to osmotic stress (from NaCl) and nitrites. However, by
omitting one outlier isolate, no significant differences in pH sensitivity were
detected between the spores or vegetative cells of C-cpe isolates versus isolates
carrying a plasmid-borne cpe gene. These results indicate that both vegetative
cells and spores of C-cpe isolates are unusually resistant to several food
preservation approaches in addition to temperature extremes. The broad-spectrum
nature of the C-cpe resistance phenotype suggests these bacteria may employ
multiple mechanisms to persist and grow in foods prior to their transmission to
humans.
PMID- 17041164
TI - Inactivation of poliovirus 1 and F-specific RNA phages and degradation of their
genomes by UV irradiation at 254 nanometers.
AB - Several models (animal caliciviruses, poliovirus 1 [PV1], and F-specific RNA
bacteriophages) are usually used to predict inactivation of nonculturable
viruses. For the same UV fluence, viral inactivation observed in the literature
varies from 0 to 5 logs according to the models and the methods (infectivity
versus molecular biology). The lack of knowledge concerning the mechanisms of
inactivation due to UV prevents us from selecting the best model. In this
context, determining if viral genome degradation may explain the loss of
infectivity under UV radiation becomes essential. Thus, four virus models (PV1
and three F-specific RNA phages: MS2, GA, and Qbeta) were exposed to UV radiation
from 0 to 150 mJ.cm-2. PV1 is the least-resistant virus, while MS2 and GA phages
are the most resistant, with phage Qbeta having an intermediate sensitivity;
respectively, 6-log, 2.3-log, 2.5-log, and 4-log decreases for 50 mJ.cm-2. In
parallel, analysis of RNA degradation demonstrated that this phenomenon depends
on the fragment size for PV1 as well as for MS2. Long fragments (above 2,000
bases) for PV1 and MS2 fell rapidly to the background level (>1.3-log decrease)
for 20 mJ.cm-2 and 60 mJ.cm-2, respectively. Nevertheless, the size of the viral
RNA is not the only factor affecting UV-induced RNA degradation, since viral RNA
was more rapidly degraded in PV1 than in the MS2 phage with a similar size.
Finally, extrapolation of inactivation and UV-induced RNA degradation kinetics
highlights that genome degradation could fully explain UV-induced viral
inactivation.
PMID- 17041165
TI - Rationale for use of Tdap booster vaccines for adolescent immunization: overview
of efficacy, safety, and clinical use.
AB - Pertussis is one of the only vaccine-preventable diseases with increasing
incidence in the United States. The incidence of pertussis infection in
adolescents is a growing concern; it can be a severe disease that may lead to
significant morbidity and mortality when transmitted to susceptible populations
(eg, infants). Experts have conceded that booster vaccination of adolescents may
considerably decrease the incidence of pertussis infections in previously
immunized, partially immunized, and nonimmunized populations. Studies in 2
tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccines licensed by
the Food and Drug Administration (FDA) have shown efficacy against pertussis
disease and have demonstrated a safety profile comparable to tetanus and
diphtheria vaccine (Td) in adolescents. Immunization schedules now include use of
Tdap vaccines for preadolescent and adolescent populations to counter the
increase in pertussis outbreaks. Challenges for clinicians include prompt
recognition of pertussis symptoms, proper diagnosis using appropriate tools, and
timely reporting of pertussis infections to surveillance bodies. Additional
studies are needed to monitor trends of pertussis incidence after implementing
the new vaccination schedule for adolescents.
PMID- 17041166
TI - Catheterization of the bladder in infants and children.
AB - Catheterization of the urinary bladder is a common procedure that can be
emotionally and physically traumatic for the child and family. The purpose of
this review is to familiarize readers with the procedure and techniques that will
minimize the physical and emotional discomfort, and complications.
PMID- 17041161
TI - Community structure analyses are more sensitive to differences in soil bacterial
communities than anonymous diversity indices.
AB - Changes in the diversity and structure of soil microbial communities may offer a
key to understanding the impact of environmental factors on soil quality in
agriculturally managed systems. Twenty-five years of biodynamic, bio-organic, or
conventional management in the DOK long-term experiment in Switzerland
significantly altered soil bacterial community structures, as assessed by
terminal restriction fragment length polymorphism (T-RFLP) analysis. To evaluate
these results, the relation between bacterial diversity and bacterial community
structures and their discrimination potential were investigated by sequence and T
RFLP analyses of 1,904 bacterial 16S rRNA gene clones derived from the DOK soils.
Standard anonymous diversity indices such as Shannon, Chao1, and ACE or
rarefaction analysis did not allow detection of management-dependent influences
on the soil bacterial community. Bacterial community structures determined by
sequence and T-RFLP analyses of the three gene libraries substantiated changes
previously observed by soil bacterial community level T-RFLP profiling. This
supported the value of high-throughput monitoring tools such as T-RFLP analysis
for assessment of differences in soil microbial communities. The gene library
approach also allowed identification of potential management-specific indicator
taxa, which were derived from nine different bacterial phyla. These results
clearly demonstrate the advantages of community structure analyses over those
based on anonymous diversity indices when analyzing complex soil microbial
communities.
PMID- 17041167
TI - Diagnosis and management of childhood bipolar disorder in the primary care
setting.
AB - Early-onset bipolar disorder (BD) is often misdiagnosed and inadequately treated
because of the varying constellation of symptoms that occur across different
developmental stages, the variety of disorders with similar presentation, and the
frequent comorbidities. The etiology of BD is complex, but research confirms the
major role that genetics and environment play in its development. The
pediatrician initially identifies most cases, with subsequent referral to mental
health providers. A complex case involving a child initially diagnosed with
attention deficit hyperactivity disorder (ADHD) and later found to have comorbid
childhood BD is considered, illustrating diagnostic considerations and
appropriate behavioral and psychopharmacological intervention.
PMID- 17041168
TI - Melatonin treatment in adolescents with delayed sleep phase syndrome.
AB - This retrospective study describes the effects of long-term treatment with
melatonin in 33 adolescents (age range, 10-18 years) with delayed sleep phase
syndrome (DSPS). Patients were treated with oral melatonin, 3 to 5 mg/day for an
average period of 6 months. During the treatment, sleep onset was advanced and
sleep duration was longer. Treatment was also associated with a decrease in the
proportion of patients reporting school difficulties. No adverse effects of
melatonin were noted. This study indicates that long-term treatment with
melatonin can be beneficial for adolescents with DSPS in terms of sleep-wake
schedule and school performance.
PMID- 17041169
TI - Atomoxetine in the management of children with ADHD: effects on quality of life
and school functioning.
AB - The purpose of this study was to examine in a controlled trial the effects of
atomoxetine on the management of attention deficit-hyperactivity disorder (ADHD)
symptoms and functional impairments at school and at home. Participants were 153
children (age 8 to 12 years) diagnosed with attention-deficit hyperactivity
disorder who were randomized to double-blind treatment with either atomoxetine (n
= 101) or placebo (n = 52). Findings revealed significant improvements both for
parent and teacher ratings of behavior for children receiving atomoxetine
therapy. Children also were reported to evidence a trend toward better response
to active medication than to placebo for health-related quality of life as rated
by parents. No significant effects were revealed for the teacher ratings of
academic productivity. Data were interpreted to provide support for the efficacy
of atomoxetine on the symptoms associated with ADHD. The effects of atomoxetine
on other functional outcomes including academic performance and health-related
outcomes are of interest, albeit less compelling for this particular
investigation, than for the effects on overt symptom display.
PMID- 17041170
TI - The attitude of physicians toward cold remedies for upper respiratory infection
in infants and children: a questionnaire survey.
AB - Over-the-counter cold remedies are widely used for symptomatic relief of upper
respiratory tract infections. The safety of these drugs is not well established
in infants and their efficacy is questionable. Our aim was to study the attitude
of family physicians and pediatricians toward the use of cold remedies in infants
and children. A questionnaire was sent to 400 family physicians and 100
pediatricians randomly selected across Ontario. The overall response rate was
53.2%. Sixteen percent of family physicians recommended cold remedies for infants
0 to 6 months of age compared to 4% of the pediatricians (P = 0.01). For infants
6 to 12 months of age, the difference between pediatricians and family physicians
persisted (14% and 38% of, respectively; P < 0.001). Despite that cold remedies
are not proven to be effective and some safety issues are associated with their
use in the pediatric age group, physicians still recommend them. Continuing
medical education programs should address the issue.
PMID- 17041171
TI - A multimedia program helps parents manage childhood aggression.
AB - Participants were 65 parents of 6- to 18-month-old children presenting for a well
child checkup between September 2002 and February 2003 to one of two private
pediatric offices. The intervention was a 30-minute multimedia program, Play
Nicely, viewed at home, which teaches the basics in childhood aggression
management. One year after intervention, parents were asked, "Do you feel that
the CD program was helpful in managing aggressive behavior in your child?" Most
(65%) parents who watched the program agreed that it helped them manage
aggression with their own child (strongly agree, 31%; agree, 34%; uncertain, 28%;
disagree, 7%; and strongly disagree, 0%). An inexpensive, brief, independently
viewed, multimedia program helps parents manage aggression in their young
children as long as 1 year after receiving it from their pediatrician. An easily
implemented intervention may contribute to violence prevention efforts.
PMID- 17041172
TI - Prenatal office practices regarding infant feeding choices.
AB - The objective of this study was to determine the obstetric care providers' roles
in breast-feeding promotion during prenatal care. A questionnaire addressing
breast-feeding issues was sent to family practitioners (FP), obstetric
gynecologists (OB/GYN), and nurse midwives (NM) in Iowa, USA. All NM, 97% of FP,
and 85% of OB/GYN reported asking infant feeding preference-usually only at the
first prenatal visit. NM (73%) were most likely to provide extensive breast
feeding counseling. OB/GYN (68%) and FP physicians (90%) reported doing their own
breast-feeding counseling. Breast examinations targeting future breast-feeding
problems were done in 82% to 84% of patients. NM practices shared more
information supportive of breast-feeding. Nearly all providers offered prenatal
classes, but only 41% of FP offered breast-feeding classes. Free formula samples
were available in 73% of FP, 54% of OB/GYN, and 36% NM offices. Pamphlets on
formula feeding and also breast-feeding were readily available. Overall NM (64%)
reported being strong breast-feeding advocates compared to only 13% of FP and 7%
of OB/GYN. In conclusion, little promotion of breast-feeding occurs in most
prenatal practice settings.
PMID- 17041173
TI - Teaching practice management skills to pediatric residents.
AB - To satisfy the core competencies required by the Pediatric Residency Review
Committee, the author describes an educational program for the residents in a
large pediatric training program. The course provides a year-long overview of
multiple medical management topics. The sessions cover nonclinical subjects
usually missed in other educational settings, with particular focus on areas of
finance, compliance, personnel management, career advancement, and leadership.
The series is currently in its third year, with a positive response from the
participants, and demonstrated improvement in resident knowledge of the covered
areas.
PMID- 17041174
TI - Infants fed docosahexaenoic acid- and arachidonic acid-supplemented formula have
decreased incidence of bronchiolitis/bronchitis the first year of life.
AB - To assess the effect of docosahexaenoic acid and arachidonic acid supplementation
in infant formula on the incidence of respiratory illnesses, pediatricians
assigned infants to receive docosahexaenoic acid/arachidonic acid-supplemented
formula or control formula. Anthropometrics, medical history, and illnesses were
reported. Among 1342 infants, there was a higher incidence of bronchiolitis in
control versus docosahexaenoic acid/arachidonic acid-supplemented groups at 5, 7,
and 9 months (P < .01). Weight, length, and head circumference were similar for
both groups. Infants fed formula supplemented with 0.32% docosahexaenoic acid and
0.64% arachidonic acid experienced a lower incidence of bronchiolitis compared
with infants fed formula supplemented with no docosahexaenoic acid/arachidonic
acid or lower levels of docosahexaenoic acid/arachidonic acid in the first year
of life.
PMID- 17041175
TI - The safety of mineral oil in the treatment of constipation--a lesson from
prolonged overdose.
AB - There have been concerns regarding the interference in the absorption of fat
soluble vitamins in long-term treatment with mineral oil; however, there is no
clear evidence in the literature to support this claim. We present a case report
illustrating the effect of prolonged (5 months) large doses of mineral oil on the
fat-soluble vitamin absorption in a 17-year-old girl.
PMID- 17041176
TI - Painless bloody nipple discharge in a 16-month-old infant.
PMID- 17041177
TI - Mollaret's meningitis due to human herpesvirus 6 in an adolescent.
AB - We report the first pediatric case of Mollaret meningitis in an adolescent female
with acute lymphoblastic leukemia in remission. This patient had signs and
symptoms consistent with meningitis, with three episodes over a 3-month period.
Human herpesvirus 6 (HHV-6) was identified during her last episode from
polymerase chain reaction assay of a cerebrospinal fluid specimen. She was
treated successfully with foscarnet, after which HHV-6 was undetectable in her
cerebrospinal fluid.
PMID- 17041178
TI - Smelling like dead fish: a case of trimethylaminuria in an adolescent.
PMID- 17041179
TI - Buttock spots.
PMID- 17041180
TI - Chronic cough.
PMID- 17041181
TI - Bullying.
PMID- 17041184
TI - Peroxisome function regulates growth on glucose in the basidiomycete fungus
Cryptococcus neoformans.
AB - The function of the peroxisomes was examined in the pathogenic basidiomycete
Cryptococcus neoformans. Recent studies reveal the glyoxylate pathway is required
for virulence of diverse microbial pathogens of plants and animals. One exception
is C. neoformans, in which isocitrate lyase (encoded by ICL1) was previously
shown not to be required for virulence, and here this was extended to exclude
also a role for malate synthase (encoded by MLS1). The role of peroxisomes, in
which the glyoxylate pathway enzymes are localized in many organisms, was
examined by mutation of two genes (PEX1 and PEX6) encoding AAA (ATPases
associated with various cellular activities)-type proteins required for
peroxisome formation. The pex1 and pex6 deletion mutants were unable to localize
the fluorescent DsRED-SKL protein to peroxisomal punctate structures, in contrast
to wild-type cells. pex1 and pex6 single mutants and a pex1 pex6 double mutant
exhibit identical phenotypes, including abolished growth on fatty acids but no
growth difference on acetate. Because both icl1 and mls1 mutants are unable to
grow on acetate as the sole carbon source, these findings demonstrate that the
glyoxylate pathway can function efficiently outside the peroxisome in C.
neoformans. The pex1 mutant exhibits wild-type virulence in a murine inhalation
model and in an insect host, demonstrating that peroxisomes are not required for
virulence under these conditions. An unusual phenotype of the pex1 and pex6
mutants was that they grew poorly with glucose as the carbon source, but nearly
wild type with galactose, which suggested impaired hexokinase function and that
C. neoformans peroxisomes might function analogously to the glycosomes of the
trypanosomid parasites. Deletion of the hexokinase HXK2 gene reduced growth in
the presence of glucose and suppressed the growth defect of the pex1 mutant on
glucose. The hexokinase 2 protein of C. neoformans contains a predicted
peroxisome targeting signal (type 2) motif; however, Hxk2 fused to fluorescent
proteins was not localized to peroxisomes. Thus, we hypothesize that glucose or
glycolytic metabolites are utilized in the peroxisome by an as yet unidentified
enzyme or regulate a pathway required by the fungus in the absence of
peroxisomes.
PMID- 17041185
TI - Parallels in fungal pathogenesis on plant and animal hosts.
PMID- 17041186
TI - Identification of translational regulation target genes during filamentous growth
in Saccharomyces cerevisiae: regulatory role of Caf20 and Dhh1.
AB - The dimorphic transition of yeast to the hyphal form is regulated by the mitogen
activated protein kinase and cyclic AMP-dependent protein kinase A pathways in
Saccharomyces cerevisiae. Signaling pathway-responsive transcription factors such
as Ste12, Tec1, and Flo8 are known to mediate filamentation-specific
transcription. We were interested in investigating the translational regulation
of specific mRNAs during the yeast-to-hyphal-form transition. Using polyribosome
fractionation and RT-PCR analysis, we identified STE12, GPA2, and CLN1 as
translation regulation target genes during filamentous growth. The transcript
levels for these genes did not change, but their mRNAs were preferentially
associated with polyribosomes during the hyphal transition. The intracellular
levels of Ste12, Gpa2, and Cln1 proteins increased under hyphal-growth
conditions. The increase in Ste12 protein level was partially blocked by
mutations in the CAF20 and DHH1 genes, which encode an eIF4E inhibitor and a
decapping activator, respectively. In addition, the caf20 and dhh1 mutations
resulted in defects in filamentous growth. The filamentation defects caused by
caf20 and dhh1 mutations were suppressed by STE12 overexpression. These results
suggest that Caf20 and Dhh1 control yeast filamentation by regulating STE12
translation.
PMID- 17041187
TI - Skp1p regulates Soi3p/Rav1p association with endosomal membranes but is not
required for vacuolar ATPase assembly.
AB - Skp1p is an essential component of SCF-type E3 ubiquitin ligase complexes and
associates with these through binding to F-box proteins. Skp1p also binds F-box
proteins in a number of non-SCF complexes. The Skp1p-associated yeast protein
Soi3p/Rav1p (hereafter referred to as Rav1p) is a component of the RAVE complex
required for regulated assembly of vacuolar ATPase (V-ATPase). Rav1p is also
involved in transport of TGN proteins and endocytic cargo between early and late
endosomes. To evaluate the role of Skp1p in the RAVE complex, we made use of the
fact that overexpression of Rav1p is toxic because it sequesters Skp1p from
essential interactions. We isolated a separation of function allele of SKP1,
skp1(Asn108Tyr), that completely abrogated the Rav1p interaction but allowed
Skp1p to perform other essential cellular functions. Cells containing the
skp1(Asn108Tyr) allele as the sole source of Skp1p exhibited normal V-ATPase
assembly and activity. However, in the skp1(Asn108Tyr) mutant strain, the
membrane-associated pool of Rav1-green fluorescent protein was increased,
suggesting that Skp1p is important for the release of Rav1p from endosomal
membranes where it functions in V-ATPase assembly. Thus, although part of the
RAVE complex, Skp1p does not appear to be involved in V-ATPase assembly but
instead in the cycling of the complex off membranes. This work also provides a
generalizable approach to defining the roles of interactions of Skp1p with
individual F-box proteins through the isolation of special alleles of SKP1.
PMID- 17041188
TI - Pheromone-induced degradation of Ste12 contributes to signal attenuation and the
specificity of developmental fate.
AB - The Ste12 transcription factor of Saccharomyces cerevisiae regulates
transcription programs controlling two different developmental fates. One is
differentiation into a mating-competent form that occurs in response to mating
pheromone. The other is the transition to a filamentous-growth form that occurs
in response to nutrient deprivation. These two distinct roles for Ste12 make it a
focus for studies into regulatory mechanisms that impart biological specificity.
The transient signal characteristic of mating differentiation led us to test the
hypothesis that regulation of Ste12 turnover might contribute to attenuation of
the mating-specific transcription program and restrict activation of the
filamentation program. We show that prolonged pheromone induction leads to
ubiquitin-mediated destabilization and decreased amounts of Ste12. This depletion
in pheromone-stimulated cultures is dependent on the mating-pathway-dedicated
mitogen-activated protein kinase Fus3 and its target Cdc28 inhibitor, Far1.
Attenuation of pheromone-induced mating-specific gene transcription (FUS1)
temporally correlates with Ste12 depletion. This attenuation is abrogated in the
deletion backgrounds (fus3Delta or far1Delta) where Ste12 is found to persist.
Additionally, pheromone induces haploid invasion and filamentous-like growth
instead of mating differentiation when Ste12 levels remain high. These
observations indicate that loss of Ste12 reinforces the adaptive response to
pheromone and contributes to the curtailing of a filamentation response.
PMID- 17041189
TI - Binding specificities and potential roles of isoforms of eukaryotic initiation
factor 4E in Leishmania.
AB - The 5' cap structure of trypanosomatid mRNAs, denoted cap 4, is a complex
structure that contains unusual modifications on the first four nucleotides. We
examined the four eukaryotic initiation factor 4E (eIF4E) homologues found in the
Leishmania genome database. These proteins, denoted LeishIF4E-1 to LeishIF4E-4,
are located in the cytoplasm. They show only a limited degree of sequence
homology with known eIF4E isoforms and among themselves. However, computerized
structure prediction suggests that the cap-binding pocket is conserved in each of
the homologues, as confirmed by binding assays to m(7)GTP, cap 4, and its
intermediates. LeishIF4E-1 and LeishIF4E-4 each bind m(7)GTP and cap 4 comparably
well, and only these two proteins could interact with the mammalian eIF4E binding
protein 4EBP1, though with different efficiencies. 4EBP1 is a translation
repressor that competes with eIF4G for the same residues on eIF4E; thus,
LeishIF4E-1 and LeishIF4E-4 are reasonable candidates for serving as translation
factors. LeishIF4E-1 is more abundant in amastigotes and also contains a typical
3' untranslated region element that is found in amastigote-specific genes.
LeishIF4E-2 bound mainly to cap 4 and comigrated with polysomal fractions on
sucrose gradients. Since the consensus eIF4E is usually found in 48S complexes,
LeishIF4E-2 could possibly be associated with the stabilization of trypanosomatid
polysomes. LeishIF4E-3 bound mainly m(7)GTP, excluding its involvement in the
translation of cap 4-protected mRNAs. It comigrates with 80S complexes which are
resistant to micrococcal nuclease, but its function is yet unknown. None of the
isoforms can functionally complement the Saccharomyces cerevisiae eIF4E,
indicating that despite their structural conservation, they are considerably
diverged.
PMID- 17041191
TI - Intratumoral heterogeneity of her-2/neu in invasive mammary carcinomas using
fluorescence in-situ hybridization and tissue microarray.
AB - Fluorescence in-situ hybridization is increasingly being used to determine HER
2/neu status in patients with breast carcinoma. The possibility that intratumoral
heterogeneity of HER-2/neu gene amplification may potentially contribute to
inaccurate assessment of HER-2/neu status was investigated in routine cases of
invasive mammary carcinomas. From 169 representative formalin-fixed, paraffin
embedded blocks of invasive duct mammary carcinomas with grade 3 architecture, 48
cases were analyzed by fluorescence in-situ hybridization and 59 analyses were
performed. Intratumoral heterogeneity for HER-2/neu gene amplification was
demonstrated in only 5 (16%) of 31 cases where morphologically similar areas of a
single tumor were analyzed. We conclude from this study that intratumoral
heterogeneity of HER-2/neu gene amplification is a demonstrable but relatively
uncommon occurrence. For invasive mammary carcinomas, the accurate assessment of
HER-2/neu status by fluorescence in-situ hybridization analysis is not
significantly confounded by intratumoral heterogeneity of HER-2/neu gene
amplification in individual tumors.
PMID- 17041190
TI - Transcriptional regulation of MDR1, encoding a drug efflux determinant, in
fluconazole-resistant Candida albicans strains through an Mcm1p binding site.
AB - Constitutive, high-level transcription of the gene encoding the drug efflux
facilitator Mdr1p is commonly observed in laboratory and clinical strains of
Candida albicans that are resistant to the antifungal drug fluconazole (FLC). In
five independently isolated FLC(R) laboratory strains, introduction of a wild
type MDR1 promoter fragment fused to the yeast enhanced green fluorescent protein
(yEGFP) reporter gene resulted in high-level expression of GFP, demonstrating
that overexpression of MDR1 is dependent on a trans-acting factor. This study
identified a 35-bp MDR1 promoter element, termed the MDRE, that mediates high
level MDR1 transcription. When inserted into a heterologous promoter, the MDRE
was sufficient to mediate high-level expression of the yEGFP reporter gene
specifically in MDR1 trans-activation strains. The MDRE promoted transcription in
an orientation-independent and dosage-dependent manner. Deletion of the MDRE in
the full-length promoter did not abolish MDR1 trans-activation, indicating that
elements upstream of the MDRE also contribute to transcription of MDR1 in these
overexpression strains. Analysis of the MDRE sequence indicated that it contains
an Mcm1p binding site very similar in organization to the site seen upstream of
the Saccharomyces cerevisiae MFA1 and STE2 genes. Electrophoretic mobility shift
analysis demonstrated that both wild-type, FLC-sensitive and MDR1 trans
activated, FLC-resistant strains contain a factor that binds the MDRE. Depletion
of Mcm1p, by use of a strain in which MCM1 expression is under the control of a
regulated promoter (44), resulted in a loss of MDRE binding activity. Thus, the
general transcription factor Mcm1p participates in the regulation of MDR1
expression.
PMID- 17041192
TI - Critical comparison of 31 commercially available digital slide systems in
pathology.
AB - Advances in new technologies for complete slide digitization in pathology have
allowed the appearance of a wide spectrum of technologic solutions for whole
slide scanning, which have been classified into motorized microscopes and
scanners. This article describes technical aspects of 31 different digital
microscopy systems. The most relevant characteristics of the scanning devices are
described, including the cameras used, the speed of digitization, and the image
quality. Other aspects, such as the file format, the compression techniques, and
the solutions for visualization of digital slides, (including diagnosis-aided
tools) are also considered. Most of the systems evaluated allow a high-resolution
digitization of the whole slide within about 1 hour using a x40 objective. The
image quality of the current virtual microscopy systems is suitable for clinical,
educational, and research purposes. The efficient use of digital microscopy by
means of image analysis systems can offer important benefits to pathology
departments.
PMID- 17041193
TI - Predicting sentinel lymph node metastases in infiltrating breast carcinoma with
vascular invasion.
AB - Sentinel lymph node and clinically negative axillary node status was compared
with well-known clinicopathological characteristics such as tumor size,
histologic and nuclear grade, lymphovascular invasion, steroid receptor, and HER
2 status in patients with breast cancer (pT1 and pT2). Positive sentinel lymph
nodes were found in 29 of 100 patients: 19 with metastases detected by
hematoxylin and eosin staining and 10 with micrometastases confirmed by
immunohistochemistry with cytokeratin. Positive sentinel lymph nodes were present
in larger carcinomas (P < 0.03), more frequently in tumors with negative PR
status (P < 0.037) and evident lymphovascular invasion (P < 0.002).
Lymphovascular invasion was also associated with breast cancer of higher
histologic (P = 0.011) and nuclear grade (P = 0.039). Tumor size and the presence
of lymphovascular invasion were found to be significant predictors of
pathologically positive sentinel lymph node in T1 and T2.
PMID- 17041194
TI - The correlation between the tumor necrosis and renal artery changes in renal cell
carcinoma.
AB - Necrosis, cysts, hemorrhage, and calcification represent common findings in renal
cell carcinoma. Different lesions, including arteriosclerosis or fibromuscular
dysplasia, or both, may involve the main renal artery. This study analyzed the
relationship between the presence and extent of necrosis in renal cell carcinoma
with renal artery changes in a consecutive series of 112 patients (71 men, 41
women) with mean renal cell carcinoma of 7.7 cm (range, 2 to 20 cm). Necrosis was
seen macroscopically and confirmed microscopically in 88 cases (78.6%), with 64
tumors having less than 50% and 24 more than 50% necrosis. Fibromuscular
dysplasia was found in 41 patients (36.6%; 17 men, 24 women) and atherosclerotic
changes in 21 patients (18.8%; 18 men, 3 women). The results suggest that
necrosis of renal cell carcinoma was significantly more common in women with
associated fibromuscular dysplasia (especially type I) and men with
atherosclerotic changes of renal artery.
PMID- 17041196
TI - Images in pathology. Endometrial stromal sarcoma with hyalinizing giant rosettes
and separate leiomyoma with palisading nuclei in the same uterus.
PMID- 17041195
TI - Benign schwannoma with perineurioma-like areas: A clinicopathologic study of 11
cases.
AB - Eleven schwannomas are described. All tumors were well demarcated and surrounded
by a true capsule or pseudocapsule and manifested Antoni A and Antoni B areas,
Verocay bodies, and hyalinized vessels. In addition to typical schwannoma, there
were clear cell areas composed of spindled cells arranged either in parallel
sheets or in loops within the myxoid matrix, morphologically identical to
retiform (reticular) perineurioma. The Schwann cells in the conventional
schwannomatous areas displayed typical ultrastructural features. Those comprising
the perineurioma-like areas revealed a primitive morphology. They were slender or
polygonal and were devoid of an external lamina, pinocytic vesicles, or
junctions. These findings suggest that the perineurioma-like areas consist of
primitive or modified Schwann cells, or, alternatively, these perineurioma-like
areas represent true, but incomplete perineurial differentiation within otherwise
ordinary benign schwannomas. These neoplasms represent a morphologic variant of
schwannoma having distinctive perineurial-like areas, a pattern which may elicit
diagnostic difficulties.
PMID- 17041198
TI - Images in pathology. Histiocytic lymphadenopathy secondary to metallosis
following hip replacement.
PMID- 17041199
TI - Images in pathology. Spontaneous coronary artery dissection as cause of sudden
cardiac death in a young woman with oral contraceptive use.
PMID- 17041200
TI - Images in pathology. Glomangioma of the sural nerve.
PMID- 17041202
TI - Images in pathology. Invasive squamous cell carcinoma of vulva that wanted to be
a puppy.
PMID- 17041203
TI - Synchronous sporadic carcinoma and primary hyperplasia of the parathyroid glands:
A case report and review of the literature.
AB - Parathyroid carcinoma is the least common endocrine malignancy. Although it has
been noted to be associated with certain clinical factors, such as familial hyper
parathyroidism, its etiology remains unknown. In rare instances, particularly in
patients with chronic renal failure, it has been proposed that parathyroid
carcinoma can arise from malignant transformation of benign lesions. We present a
case of synchronous malignant and primary hyperplastic parathyroid disease in a
patient with normal renal function. A 46-year-old woman was seen with symptomatic
refractory hypercalcemia. Investigations suggested a hyperactive parathyroid
gland. Operative findings were of a low-grade parathyroid carcinoma in
concurrence with diffuse hyperplasia of the remaining glands. To our knowledge
this represents the fifth reported case. The possibility of malignant change in
hyperplastic parathyroid tissue has implications for patient management and
follow-up, particularly if tissue is left in situ to maintain hormonal function.
PMID- 17041204
TI - Epithelioid hemangioendothelioma of the spinal cord: Description of a case with
cytogenetic analysis.
AB - A case of epithelioid hemangioendothelioma of the cauda equina is reported. The
patient presented with rapidly worsening low back pain. Magnetic resonance
imaging revealed a sharply demarcated intradural lumbar lesion. A bluish-red
lesion, attached to the filum terminale, was removed. The patient is alive
without evidence of recurrence 18 months after surgery. The tumor was composed of
variously sized vessels lined by epithelioid endothelial cells with clear
cytoplasm and centrally located, moderately atypical nuclei. These cells were
immunoreactive for CD31 and factor VIII antibodies. Cytogenetic analysis
disclosed two clones: 44-45X, - Y [cp3]/46XY[11]. Epithelioid
hemangioendothelioma may arise in several sites, the most common being soft
tissues. It is a borderline tumor that may recur, may metastasize, and rarely
causes death. The present case appears to be the first example of epithelioid
hemangioendothelioma of the spinal cord.
PMID- 17041205
TI - Leydig cell tumor of the testis with histological and immunohistochemical
features of malignancy in a 1-year-old boy with isosexual pseudoprecocity.
AB - The article reports the clinical, histopathological, and immunohistochemical
findings of a 1-year-old boy presenting with isosexual pseudoprecocity
attributable to a functioning Leydig cell tumor of the testis. The case appears
to represent the youngest patient ever recognized with this well-known syndrome.
Malignancy features were also for the first time initially assessed using
criteria, retrospectively developed from the literature, for metastasizing Leydig
cell tumor. All the following were found: infiltrative borders, cellular
pleomorphism, high mitotic index (12-14/high-power field), high MIB-1 index
(40%), P53 positivity in 50% of the cells, and bcl-2 positivity in 15% of the
cells. Immunohistochemistry proved the cells of the tumor to be positive for
inhibin, Melan-A, synaptophysin, cytokeratin, and calretinin and negative for S
100 and chromogranin A. Notably, lipochrome and crystals of Reinke were not found
in the tumor cells. Although the neoplasm fulfilled the criteria for a
potentially metastasizing Leydig cell tumor, there was no evidence of that event
having occurred, perhaps as a result of early treatment or as indication that
criteria developed for Leydig cell tumor of adults may not apply to children.
PMID- 17041206
TI - Isolated hepatic involvement of cat scratch disease in immunocompetent adults:
Enhanced magnetic resonance imaging, pathological findings, and molecular
analysis--two cases.
AB - Visceral involvement in absence of lymphadenopathy is a rare manifestation in cat
scratch disease; hepatic granulomas are rare, representing 0.3% of systemic
manifestations of cat scratch disease, and gallbladder extension is a singular
case. The present article refers to 2 rare cases of visceral cat scratch disease
in immunocompetent adults with hepatic granulomatous inflammation, caused by
Bartonella henselae infection, with gallbladder involvement in 1 case and no
lymphadenopathy. Histological features demonstrated the presence of inflammatory
necrotizing granulomatous nonneoplastic process. Molecular studies (polymerase
chain reaction) were performed to confirm the infectious etiology.
PMID- 17041207
TI - Ectopic modified sebaceous glands in human penis.
AB - The balanopreputial sulcus is believed to be the most frequent site of the so
called Tyson's glands. The intriguing feature of these anatomical structures is
their mere existence, which has been doubted. Herein, the authors present a case
of a 24-year-old man who underwent surgical treatment of his phimosis. On
microscopic examination of the specimen, glands with morphological features
similar to those described by Tyson were noted.
PMID- 17041211
TI - Molecular evolution of hepatitis B virus over 25 years.
AB - Determining the longitudinal molecular evolution of hepatitis B virus (HBV) is
difficult due to HBV's genomic complexity and the need to study paired samples
collected over long periods of time. In this study, serial samples were collected
from eight hepatitis B virus e antigen-negative asymptomatic carriers of HBV
genotype B in 1979 and 2004, thus providing a 25-year period to document the long
term molecular evolution of HBV. The rate, nature, and distribution of mutations
that emerged over 25 years were determined by phylogenetic and linear regression
analysis of full-length HBV genome sequences. Nucleotide hypervariability was
observed within the polymerase and pre-S/S overlap region and within the core
gene. The calculated mean number of nucleotide substitutions/site/year (7.9 x 10(
5)) was slightly higher than published estimates (1.5 x 10(-5) to 5 x 10(-5)).
Nucleotide changes in the quasispecies population did not significantly alter the
molecular evolutionary rate, based on linear regression analysis of evolutionary
distances among serial clone pre-S region sequences. Therefore, the directly
amplified or dominant sequence was sufficient to estimate the putative molecular
evolutionary rate for these long-term serial samples. On average, the ratio of
synonymous (dS) to nonsynonymous (dN) substitutions was highest for the
polymerase-coding region and lowest for the core-coding region. The low dS/dN
ratios observed within the core suggest that selection occurs within this gene
region, possibly as an immune evasion strategy. The results of this study suggest
that HBV sequence divergence may occur more rapidly than previously estimated, in
a host immune phase-dependent manner.
PMID- 17041210
TI - Nonsegmented negative-strand viruses as vaccine vectors.
PMID- 17041212
TI - Identifying epitopes responsible for neutralizing antibody and DC-SIGN binding on
the spike glycoprotein of the severe acute respiratory syndrome coronavirus.
AB - The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) uses
dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) to facilitate cell
entry via cellular receptor-angiotensin-converting enzyme 2. For this project, we
used recombinant baculoviruses expressing different lengths of SARS-CoV spike (S)
protein in a capture assay to deduce the minimal DC-SIGN binding region. Our
results identified the region location between amino acid (aa) residues 324 to
386 of the S protein. We then generated nine monoclonal antibodies (MAbs) against
the S protein to map the DC-SIGN-binding domain using capture assays with
pseudotyped viruses and observed that MAb SIa5 significantly blocked S protein-DC
SIGN interaction. An enhancement assay using the HKU39849 SARS-CoV strain and
human immature dendritic cells confirmed our observation. Data from a pepscan
analysis and M13 phage peptide display library system mapped the reactive MAb
SIa5 epitope to aa residues 363 to 368 of the S protein. Results from a capture
assay testing three pseudotyped viruses with mutated N-linked glycosylation sites
of the S protein indicate that only two pseudotyped viruses (N330Q and N357Q,
both of which lost glycosylation sites near the SIa5 epitope) had diminished DC
SIGN-binding capacity. We also noted that MAb SIb4 exerted a neutralizing effect
against HKU39849; its reactive epitope was mapped to aa residues 435 to 439 of
the S protein. We offer the data to facilitate the development of therapeutic
agents and preventive vaccines against SARS-CoV infection.
PMID- 17041213
TI - Postentry events are responsible for restriction of productive varicella-zoster
virus infection in Chinese hamster ovary cells.
AB - Productive infection of varicella-zoster virus (VZV) in vitro is restricted
almost exclusively to cells derived from humans and other primates. We
demonstrate that the restriction of productive VZV infection in CHO-K1 cells
occurs downstream of virus entry. Entry of VZV into CHO-K1 cells was
characterized by utilizing an ICP4/beta-galactosidase reporter gene that has been
used previously to study herpes simplex virus type 1 entry. Entry of VZV into CHO
K1 cells involved cell surface interactions with heparan sulfate
glycosaminoglycans and a cation-independent mannose-6-phosphate receptor.
Lysosomotropic agents inhibited the entry of VZV into CHO-K1 cells, consistent
with a low-pH-dependent endocytic mechanism of entry. Infection of CHO-K1 cells
by VZV resulted in the production of both immediate early and late gene products,
indicating that a block to progeny virus production occurs after the initiation
of virus gene expression.
PMID- 17041214
TI - Administration of fludarabine-loaded autologous red blood cells in simian
immunodeficiency virus-infected sooty mangabeys depletes pSTAT-1-expressing
macrophages and delays the rebound of viremia after suspension of antiretroviral
therapy.
AB - A major limitation of highly active antiretroviral therapy is that it fails to
eradicate human immunodeficiency virus (HIV) infection due to its limited effects
on viral reservoirs carrying replication-competent HIV, including
monocytes/macrophages (M/M). Therefore, therapeutic approaches aimed at targeting
HIV-infected M/M may prove useful in the clinical management of HIV-infected
patients. In previous studies, we have shown that administration of fludarabine
loaded red blood cells (RBC) in vitro selectively induces cell death in HIV
infected M/M via a pSTAT1-dependent pathway. To determine the in vivo efficacy of
this novel therapeutic strategy, we treated six naturally simian immunodeficiency
virus (SIV)-infected sooty mangabeys (SMs) with either 9-[2-(R)
(phosphonomethoxy)propyl]adenine (PMPA) only, fludarabine-loaded RBC only, or
PMPA in association with fludarabine-loaded RBC. The rationale of this treatment
was to target infected M/M with fludarabine-loaded RBC at a time when PMPA is
suppressing viral replication taking place in activated CD4+ T cells. In vivo
administration of fludarabine-loaded RBC was well tolerated and did not induce
any discernible side effect. Importantly, addition of fludarabine-loaded RBC to
PMPA delayed the rebound of viral replication after suspension of therapy, thus
suggesting a reduction in the size of SIV reservoirs. While administrations of
fludarabine-loaded RBC did not induce any change in the CD4+ or CD8+ T-cell
compartments, we observed, in chronically SIV-infected SMs, a selective depletion
of M/M expressing pSTAT1. This study suggests that therapeutic strategies based
on the administration of fludarabine-loaded RBC may be further explored as
interventions aimed at reducing the size of the M/M reservoirs during chronic HIV
infection.
PMID- 17041216
TI - Identification of major histocompatibility complex class II-restricted antigens
and epitopes of the Epstein-Barr virus by a novel bacterial expression cloning
approach.
AB - Epstein-Barr virus (EBV)-specific T cells have been successfully used to treat or
prevent EBV-positive lymphoproliferative disease in hematopoietic stem cell
transplant recipients, but the antigens recognized by the infused CD4+ T cells
have remained unknown. Here, we describe a simple procedure that permits the
identification of viral T-helper (TH)-cell antigens and epitopes. This direct
antigen identification method is based on the random expression of viral
polypeptides fused to chloramphenicol acetyltransferase (CAT) in bacteria, which
are subsequently fed to major histocompatibility complex class II+ antigen
presenting cells and probed with antigen-specific T cells. The fusion of
antigenic fragments to CAT offers several advantages. First, chloramphenicol
treatment allows the selection of bacteria expressing antigen-CAT fusion proteins
in frame, which greatly reduces the number of colonies to be screened. Second,
antigenic fragments fused to CAT are expressed at high levels, even when derived
from proteins that are toxic to bacteria. Third, the uniformly high expression
level of antigen-CAT fusion proteins permits the establishment of large and
representative pool sizes. Finally, antigen identification does not require
knowledge of the restriction element and often leads directly to the
identification of the T-cell epitope. Using this approach, the BALF4 and BNRF1
proteins were identified as targets of the EBV-specific T-helper-cell response,
demonstrating that lytic cycle antigens are a relevant component of the EBV
specific TH-cell response.
PMID- 17041215
TI - Host cell DNA repair pathways in adeno-associated viral genome processing.
AB - Recentstudies have shown that wild-type and recombinant adeno-associated virus
(AAV and rAAV) genomes persist in human tissue predominantly as double-stranded
(ds) circular episomes derived from input linear single-stranded virion DNA.
Using self-complementary recombinant AAV (scAAV) vectors, we generated
intermediates that directly transition to ds circular episomes. The scAAV genome
ends are palindromic hairpin-structured terminal repeats, resembling a double
stranded break repair intermediate. Utilizing this substrate, we found cellular
DNA recombination and repair factors to be essential for generating circular
episomal products. To identify the specific cellular proteins involved, the scAAV
circularization-dependent vector was used as a reporter in 19 mammalian DNA
repair-deficient cell lines. The results show that RecQ helicase family members
(BLM and WRN), Mre11 and NBS1 of the Mre11-Rad50-Nbs1 (MRN) complex, and ATM are
required for efficient scAAV genome circularization. We further demonstrated that
the scAAV genome requires ATM and DNA-PK(CS), but not NBS1, to efficiently
convert to a circular form in nondividing cells in vivo using transgenic mice.
These studies identify specific pathways involved for further elucidating viral
and cellular mechanisms of DNA maintenance important to the viral life cycle and
vector utilizations.
PMID- 17041217
TI - Antilipopolysaccharide factor interferes with white spot syndrome virus
replication in vitro and in vivo in the crayfish Pacifastacus leniusculus.
AB - In a study of genes expressed differentially in the freshwater crayfish
Pacifastacus leniusculus infected experimentally with the white spot syndrome
virus (WSSV), one protein, known as antilipopolysaccharide factor (ALF), was
chosen, among those whose transcript levels increased upon viral infection, for
further studies. ALF RNA interference (RNAi) experiments in whole animals and in
cell cultures indicated that ALF can protect against WSSV infection, since
knockdown of ALF by RNAi specifically resulted in higher rates of viral
propagation. In a cell culture of hematopoietic tissue (Hpt) from P. leniusculus,
quantitative PCR showed that knockdown of ALF by RNAi resulted into WSSV levels
that were about 10-fold higher than those treated with control double-stranded
RNA (dsRNA). In addition, RNAi experiments with other crayfish genes that had
been found to be up-regulated by a WSSV infection did not result in any changes
of viral loads. Thus, the cell culture does not respond to dsRNA in a similar
manner, as shown earlier for dsRNA injected into shrimp, which gave a higher
degree of resistance to WSSV infection. If ALF transcription in whole animals was
stimulated by the administration of UV-treated WSSV, a partial protection against
a subsequent challenge with the active virus was conferred to the host. This is
the first crustacean gene product identified with the capacity to interfere with
replication of this important pathogen.
PMID- 17041218
TI - Pathogenesis of a genogroup II human norovirus in gnotobiotic pigs.
AB - We evaluated the gnotobiotic (Gn) pig as a model to study the pathogenesis of
human norovirus (HuNoV) and to determine the target cells for viral replication.
Sixty-five Gn pigs were inoculated with fecal filtrates of the
NoV/GII/4/HS66/2001/US strain or with pig-passaged intestinal contents (IC) and
euthanized acutely (n = 43) or after convalescence (n = 22). Age-matched Gn
piglets (n = 14) served as mock-inoculated controls. Seventy-four percent (48/65)
of the inoculated animals developed mild diarrhea compared to 0 of 14 controls.
Pigs from postinoculation days (PID) 1 to 4 tested positive for HuNoV by reverse
transcription-PCR of rectal swab fluids (29/65) and IC (9/43) and by antigen (Ag)
enzyme-linked immunosorbent assay (ELISA) using antiserum to virus-like particles
of HuNoV GII/4. No control pigs were positive. Histopathologic examination showed
mild lesions in the proximal small intestine of only one pig (1/7).
Seroconversion after PID 21 was detected by antibody ELISA in 13 of 22 virus
inoculated pigs (titers, 1:20 to 1:200) but not in controls. Immunofluorescent
microscopy using a monoclonal antibody to HuNoV GII capsid revealed patchy
infection of duodenal and jejunal enterocytes of 18 of 31 HuNoV-inoculated pigs
with a few stained cells in the ileum and no immunofluorescence (IF) in mock
inoculated controls. Immunofluorescent detection of the viral nonstructural N
terminal protein antigen in enterocytes confirmed translation. Transmission
electron microscopy of intestines from HuNoV-inoculated pigs showed disrupted
enterocytes, with cytoplasmic membrane vesicles containing calicivirus-like
particles of 25 to 40 nm in diameter. In summary, serial passage of HuNoV in
pigs, with occurrence of mild diarrhea and shedding, and immunofluorescent
detection of the HuNoV structural and nonstructural proteins in enterocytes
confirm HuNoV replication in Gn pigs.
PMID- 17041219
TI - Murine hepatitis virus strain 1 produces a clinically relevant model of severe
acute respiratory syndrome in A/J mice.
AB - Severe acute respiratory syndrome (SARS) is a life-threatening infectious disease
which has been difficult to study and treat because of the lack of a readily
available animal model. Intranasal infection of A/J mice with the coronavirus
murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features
of SARS. All MHV-1-infected A/J mice developed progressive interstitial
pneumonitis, including dense macrophage infiltrates, giant cells, and hyaline
membranes, resulting in death of all animals. In contrast, other mouse strains
developed only mild transitory disease. Infected A/J mice had significantly
higher cytokine levels, particularly macrophage chemoattractant protein 1 (MCP
1/CCL-2), gamma interferon, and tumor necrosis factor alpha. Furthermore,
FGL2/fibroleukin mRNA transcripts and protein and fibrin deposits were markedly
increased in the lungs of infected A/J mice. These animals developed a less
robust type I interferon response to MHV-1 infection than resistant C57BL/6J
mice, and treatment with recombinant beta interferon improved survival. This
study describes a potentially useful small animal model of human SARS, defines
its pathogenesis, and suggests treatment strategies.
PMID- 17041220
TI - Human immunodeficiency virus type 1 Gag polyprotein modulates its own
translation.
AB - The full-length viral RNA of human immunodeficiency virus type 1 (HIV-1)
functions both as the mRNA for the viral structural proteins Gag and Gag/Pol and
as the genomic RNA packaged within viral particles. The packaging signal which
Gag recognizes to initiate genome encapsidation is in the 5' untranslated region
(UTR) of the HIV-1 RNA, which is also the location of translation initiation
complex formation. Hence, it is likely that there is competition between the
translation and packaging processes. We studied the ability of Gag to regulate
translation of its own mRNA. Gag had a bimodal effect on translation from the HIV
1 5' UTR, stimulating translation at low concentrations and inhibiting
translation at high concentrations in vitro and in vivo. The inhibition was
dependent upon the ability of Gag to bind the packaging signal through its
nucleocapsid domain. The stimulatory activity was shown to depend on the matrix
domain of Gag. These results suggest that Gag controls the equilibrium between
translation and packaging, ensuring production of enough molecules of Gag to make
viral particles before encapsidating its genome.
PMID- 17041221
TI - Regulation of inducible nitric oxide synthase expression by viral A238L-mediated
inhibition of p65/RelA acetylation and p300 transactivation.
AB - Uncontrolled generation of nitric oxide (NO) by inducible nitric-oxide synthase
(iNOS) can cause damage to host cells and inflammation, two undesirable events
for virus spreading. African swine fever virus (ASFV) infection regulates iNOS
induced gene expression through the synthesis of the A238L virus protein. We here
explored the role of A238L, an NF-kappaB and NFAT inhibitor, in the regulation of
iNOS transcription in macrophages. NO production and iNOS mRNA and protein levels
as well as iNOS promoter activity after lipopolysaccharide (LPS)-gamma interferon
(IFN-gamma) treatment were down-regulated both during ASFV infection and in Raw
264.7 cells stably expressing the viral protein. Overexpression of p300, but not
of a histone acetyltransferase (HAT) defective mutant, reverted the A238L
mediated inhibition of both basal and LPS-IFN-gamma-induced iNOS promoter
activity. Following stimulation with LPS-IFN-gamma, p65 and p300 interaction was
abolished in Raw-A238L cells. Expression of A238L also inhibited p65/relA and
p300 binding to the distal NF-kappaB sequence of the iNOS promoter together with
p65 acetylation. Finally, A238L abrogated p300 transactivation mediated by a GAL4
p300 construction. These results provide evidence for an unique viral mechanism
involved in transcriptional regulation of iNOS gene expression.
PMID- 17041222
TI - Macrophage transcriptional responses following in vitro infection with a highly
virulent African swine fever virus isolate.
AB - We used a porcine microarray containing 2,880 cDNAs to investigate the response
of macrophages to infection by a virulent African swine fever virus (ASFV)
isolate, Malawi LIL20/1. One hundred twenty-five targets were found to be
significantly altered at either or both 4 h and 16 h postinfection compared with
targets after mock infection. These targets were assigned into three groups
according to their temporal expression profiles. Eighty-six targets showed
increased expression levels at 4 h postinfection but returned to expression
levels similar to those in mock-infected cells at 16 h postinfection. These
encoded several proinflammatory cytokines and chemokines, surface proteins, and
proteins involved in cell signaling and trafficking pathways. Thirty-four targets
showed increased expression levels at 16 h postinfection compared to levels at 4
h postinfection and in mock-infected cells. One host gene showed increased
expression levels at both 4 and 16 h postinfection compared to levels in mock
infected cells. The microarray results were validated for 12 selected genes by
quantitative real-time PCR. Levels of protein expression and secretion were
measured for two proinflammatory cytokines, interleukin 1beta and tumor necrosis
factor alpha, during a time course of infection with either the virulent Malawi
LIL20/1 isolate or the OUR T88/3 nonpathogenic isolate. The results revealed
differences between these two ASFV isolates in the amounts of these cytokines
secreted from infected cells.
PMID- 17041223
TI - Integrity of membrane lipid rafts is necessary for the ordered assembly and
release of infectious Newcastle disease virus particles.
AB - Membrane lipid raft domains are thought to be sites of assembly for many
enveloped viruses. The roles of both classical lipid rafts and lipid rafts
associated with the membrane cytoskeleton in the assembly of Newcastle disease
virus (NDV) were investigated. The lipid raft-associated proteins caveolin-1,
flotillin-2, and actin were incorporated into virions, while the non-lipid raft
associated transferrin receptor was excluded. Kinetic analyses of the
distribution of viral proteins in lipid rafts, as defined by detergent-resistant
membranes (DRMs), in non-lipid raft membranes, and in virions showed an
accumulation of HN, F, and NP viral proteins in lipid rafts early after
synthesis. Subsequently, these proteins exited the DRMs and were recovered
quantitatively in purified virions, while levels of these proteins in detergent
soluble cell fractions remained relatively constant. Cholesterol depletion of
infected cells drastically altered the association of viral proteins with DRMs
and resulted in an enhanced release of virus particles with reduced infectivity.
Decreased infectivity was not due to effects on subsequent virus entry, since the
extraction of cholesterol from intact virus did not significantly reduce
infectivity. Particles released from cholesterol-depleted cells had very
heterogeneous densities and altered ratios of NP and glycoproteins, demonstrating
structural abnormalities which potentially contributed to their lowered
infectivity. Taken together, these results indicate that lipid rafts, including
cytoskeleton-associated lipid rafts, are sites of NDV assembly and that these
domains are important for ordered assembly and release of infectious Newcastle
disease virus particles.
PMID- 17041224
TI - PmRab7 is a VP28-binding protein involved in white spot syndrome virus infection
in shrimp.
AB - Our aim was to isolate and characterize white spot syndrome virus (WSSV)-binding
proteins from shrimp. After a blot of shrimp hemocyte membrane proteins was
overlaid with a recombinant WSSV envelope protein (rVP28), the reactive bands on
the blot were detected using anti-VP28 antibody. Among three membrane-associated
molecules identified by liquid chromatography-tandem mass spectrometry, there was
a 25-kDa protein that bound to both rVP28 and WSSV. Since it had a primary
structure with high homology to the small GTP-binding protein Rab7, we named it
Penaeus monodon Rab7 (PmRab7). The full-length PmRab7 cDNA was obtained, and
results from a glutathione S-transferase pull-down assay confirmed specific
binding to rVP28. Reverse transcriptase PCR analysis revealed PmRab7 expression
in many tissues, and real-time PCR analysis revealed that expression was
constitutive. Binding of PmRab7 to rVP28 or WSSV occurred in a dose-dependent
manner and was inhibited by anti-Rab7 antibody. In an in vivo neutralization
assay, the number of dead shrimp after challenge with WSSV plus PmRab7 (15%) or
WSSV plus anti-Rab7 antibody (5%) was significantly lower than after challenge
with WSSV alone (95%). In contrast to the WSSV-injected group, shrimp injected
with WSSV plus PmRab7 or WSSV plus anti-Rab7 showed no WSSV-type histopathology.
We conclude that PmRab7 is involved in WSSV infection in shrimp. This is the
first study to identify a shrimp protein that binds directly to a major viral
envelope protein of WSSV.
PMID- 17041225
TI - At least 50% of human-specific HERV-K (HML-2) long terminal repeats serve in vivo
as active promoters for host nonrepetitive DNA transcription.
AB - We report the first genome-wide comparison of in vivo promoter activities of a
group of human-specific endogenous retroviruses in healthy and cancerous germ
line tissues. To this end, we employed a recently developed technique termed
genomic repeat expression monitoring. We found that at least 50% of human
specific long terminal repeats (LTRs) possessed promoter activity, and many of
them were up- or downregulated in a seminoma. Individual LTRs were expressed at
markedly different levels, ranging from approximately 0.001 to approximately 3%
of the housekeeping beta-actin gene transcript level. We demonstrated that the
main factors affecting the LTR promoter activity were the LTR type (5'-proviral,
3' proviral, or solitary) and position with regard to genes. The averaged
promoter strengths of solitary and 3'-proviral LTRs were almost identical in both
tissues, whereas 5'-proviral LTRs displayed two- to fivefold higher promoter
activities. The relative content of promoter-active LTRs in gene-rich regions was
significantly higher than that in gene-poor loci. This content was maximal in
those regions where LTRs "overlapped" readthrough transcripts. Although many
promoter-active LTRs were mapped near known genes, no clear-cut correlation was
observed between transcriptional activities of genes and neighboring LTRs. Our
data also suggest a selective suppression of transcription for LTRs located in
gene introns.
PMID- 17041226
TI - Human cytomegalovirus IE86 attenuates virus- and tumor necrosis factor alpha
induced NFkappaB-dependent gene expression.
AB - Human cytomegalovirus (HCMV) infection regulates a number of genes involved in
the host antiviral response. We have previously reported that HCMV attenuates the
expression of beta interferon (IFN-beta) and a number of proinflammatory
chemokines, and this attenuation is mediated by the HCMV immediate-early protein
IE86. The present study seeks to identify the mechanism by which IE86 blocks IFN
beta expression. We demonstrate that the induction of IFN-beta during HCMV
infection requires the activation of both the IRF-3 and the NFkappaB pathways.
Therefore, IE86 may target either pathway to block IFN-beta expression. Our
results show that IE86 does not block IRF-3 phosphorylation, dimerization,
nuclear translocation, or target gene expression. However, using gel shift
analysis, we demonstrate that IE86 efficiently inhibits virus-induced binding of
NFkappaB to the IFN-beta promoter, resulting in attenuation of IFN-beta and
NFkappaB-dependent gene expression. Furthermore, IE86 expression inhibits tumor
necrosis factor alpha-induced NFkappaB DNA binding and target gene expression.
Together, these results identify IE86 as a NFkappaB antagonist, which results in
the suppression of NFkappaB-dependent cytokine and chemokine gene expression.
PMID- 17041227
TI - JC virus minor capsid proteins Vp2 and Vp3 are essential for virus propagation.
AB - Virus-encoded capsid proteins play a major role in the life cycles of all
viruses. The JC virus capsid is composed of 72 pentamers of the major capsid
protein Vp1, with one of the minor coat proteins Vp2 or Vp3 in the center of each
pentamer. Vp3 is identical to two-thirds of Vp2, and these proteins share a DNA
binding domain, a nuclear localization signal, and a Vp1-interacting domain. We
demonstrate here that both the minor proteins and the myristylation site on Vp2
are essential for the viral life cycle, including the proper packaging of its
genome.
PMID- 17041229
TI - Human papillomavirus genotype 31 does not express detectable microRNA levels
during latent or productive virus replication.
AB - It has recently become clear that several pathogenic DNA viruses express virally
encoded microRNAs in infected cells. In particular, numerous microRNAs have been
identified in a range of human and animal herpesviruses, and individual microRNAs
have also been identified in members of the polyoma- and adenovirus families.
Although their functions remain largely unknown, it seems likely that these viral
microRNAs play an important role in viral replication in vivo. Here we present an
analysis of the microRNAs expressed in human cells during the latent and
productive phases of the human papillomavirus genotype 31 (HPV31) replication
cycle. Although over 500 cellular microRNAs were cloned and identified, not a
single HPV31-specific microRNA was obtained. We therefore concluded that HPV31,
and possibly human papillomaviruses in general, does not express viral microRNAs.
PMID- 17041228
TI - Novel envelope determinants for CCR3 use by human immunodeficiency virus.
AB - Human immunodeficiency virus type 1 can generally use CCR3 and CCR5 for cell
entry. We show that envelopes with novel phenotypes arise during "coreceptor
switch": one loses the ability to use CCR3 (R5-only phenotype), and another gains
use of CXCR4 in addition to CCR5 and CCR3 (R3/R5/X4-using phenotype). The
envelope determinants for CCR3 use mapped to three amino acids. One, N356 in
conserved region 3, is a potential glycosylation site and has not previously been
associated with coreceptor use. The other two, R440 and N448 in conserved region
4, are proximal to but distinct from residues already identified as being
important for CCR5 binding.
PMID- 17041230
TI - Genetic modifications of seizure susceptibility and expression by altered
excitability in Drosophila Na(+) and K(+) channel mutants.
AB - A seizure-paralysis repertoire characteristic of Drosophila "bang-sensitive"
mutants can be evoked electroconvulsively in tethered flies, in which behavioral
episodes are associated with synchronized spike discharges in different body
parts. Flight muscle DLMs (dorsal longitudinal muscles) display a stereotypic
sequence of initial and delayed bouts of discharges (ID and DD), interposed with
giant fiber (GF) pathway failure and followed by a refractory period. We examined
how seizure susceptibility and discharge patterns are modified in various K(+)
and Na(+) channel mutants. Decreased numbers of Na(+) channels in nap(ts) flies
drastically reduced susceptibility to seizure induction, eliminated ID, and
depressed DD spike generation. Mutations of different K(+) channels led to
differential modifications of the various components in the repertoire. Altered
transient K(+) currents in Sh(133) and Hk mutants promoted ID induction. However,
only Sh(133) but not Hk mutations increased DD seizure and GF pathway failure
durations. Surprisingly, modifications in sustained K(+) currents in eag and Shab
mutants increased thresholds for DD induction and GF pathway failure.
Nevertheless, both eag and Shab, like Sh(133), increased DD spike generation and
recovery time from GF pathway failure. Interactions between channel mutations
with the bang-sensitive mutation bss demonstrated the role of membrane
excitability in stress-induced seizure-paralysis behavior. Seizure induction and
discharges were suppressed by nap(ts) in bss nap double mutants, whereas Sh
heightened seizure susceptibility in bss Sh(133) and bss Sh(M) double mutants.
Our results suggest that individual seizure repertoire components reflect
different neural network activities that could be differentially altered by
mutations of specific ion channel subunits.
PMID- 17041231
TI - The occurrence and outcome of 39 pregnancies after 1621 cases of transcervical
resection of endometrium.
AB - BACKGROUND: To evaluate the outcomes and management of pregnancy after
transcervical resection of the endometrium (TCRE). METHODS: Retrospective study
of 39 pregnancies after 1621 procedures of TCRE. RESULTS: Among 1621 women who
were successfully followed up after TCRE, there were 39 pregnancies in 32 women,
including five ectopic pregnancies (12.8%) and 34 intrauterine pregnancies
(87.2%). The majority of pregnancies (84.6%) occurred within the first 2 years.
In the first year after TCRE, the incidence of pregnancy was 1.5%. In women who
had amenorrhoea after TCRE, the chances of conception (2/676; 0.3%) were
significantly (P < 0.001) lower than for those who continued to have period
(30/945; 3.2%). Thirty-two cases with intrauterine pregnancy were terminated
under ultrasound guidance with two difficult procedures. Only one pregnancy in
our study resulted in spontaneous miscarriage which was managed by suction
curettage. One term pregnancy had placenta increta resulting in Caesarean
hysterectomy. CONCLUSIONS: Pregnancies after TCRE are associated with increased
risk, and clinicians should be aware of the various complications of pregnancy
that may occur after TCRE, including an increased risk of ectopic pregnancy.
Surgical termination of pregnancy after TCRE is potentially a difficult procedure
and should be carried out under ultrasound guidance.
PMID- 17041232
TI - Can computers improve patient care by primary health care workers in India?
AB - OBJECTIVE: The objective was to test whether a decision support technology for
non-physicians can increase health care utilization and quality. DESIGN: Before
and after measurements were taken from a systematic random sample of patients and
staff at randomly assigned intervention and control facilities. SETTING: The
study took place at primary health facilities in rural Tamil Nadu, India.
PARTICIPANTS: One thousand two hundred and eighty-six patients and 82 staff were
interviewed. INTERVENTION: A computer-assisted decision support technology was
introduced to assist with patient screening. MAIN OUTCOME MEASURES: Outcome
measures included new patient visits per month, a Global Patient Assessment of
Care Index, and health worker attitude variables. RESULTS: There was a difference
of difference of 430 new patient visits per month at the intervention sites (P =
0.005), an increase from baseline of 18% at intervention sites compared with a
decline of 5% at control sites. The intervention was associated with significant
improvements in a Global Patient Assessment of Care Index (mean difference of
difference 7.9, P < 0.001). The largest gains were made in patient communication,
technical quality, and general satisfaction with care. The attitudes of public
health workers toward the new technology and their jobs did not change.
CONCLUSIONS: Decision support technologies have considerable potential to improve
coverage and quality of health care for the poor and where there is no doctor,
but the unreceptive attitude of public health workers would need to be overcome.
Application of these technologies should take advantage of their popularity with
patients and the opportunity to work through the private sector.
PMID- 17041233
TI - A graph-based motif detection algorithm models complex nucleotide dependencies in
transcription factor binding sites.
AB - Given a set of known binding sites for a specific transcription factor, it is
possible to build a model of the transcription factor binding site, usually
called a motif model, and use this model to search for other sites that bind the
same transcription factor. Typically, this search is performed using a position
specific scoring matrix (PSSM), also known as a position weight matrix. In this
paper we analyze a set of eukaryotic transcription factor binding sites and show
that there is extensive clustering of similar k-mers in eukaryotic motifs, owing
to both functional and evolutionary constraints. The apparent limitations of
probabilistic models in representing complex nucleotide dependencies lead us to a
graph-based representation of motifs. When deciding whether a candidate k-mer is
part of a motif or not, we base our decision not on how well the k-mer conforms
to a model of the motif as a whole, but how similar it is to specific, known k
mers in the motif. We elucidate the reasons why we expect graph-based methods to
perform well on motif data. Our MotifScan algorithm shows greatly improved
performance over the prevalent PSSM-based method for the detection of eukaryotic
motifs.
PMID- 17041234
TI - Solution structure of a purine rich hexaloop hairpin belonging to PGY/MDR1 mRNA
and targeted by antisense oligonucleotides.
AB - A preferential target of antisense oligonucleotides directed against human
PGY/MDR1 mRNA is a hairpin containing a stem with a G*U wobble pair, capped by
the purine-rich 5'r(GGGAUG)3' hexaloop. This hairpin is studied by
multidimensional NMR and restrained molecular dynamics, with special emphasis on
the conformation of south sugars and non-standard phosphate linkages evidenced in
both the stem and the loop. The hairpin is found to be highly structured. The G*U
wobble pair, a strong counterion binding site, displays structural
particularities that are characteristic of this type of mismatch. The upper part
of the stem undergoes distortions that optimize its interactions with the
beginning of the loop. The loop adopts a new fold in which the single-stranded
GGGA purine tract is structured in A-like conformation stacked in continuity of
the stem and displays an extensive hydrogen bonding surface for recognition. The
remarkable hairpin stability results from classical inter- and intra-strand
interactions reinforced by numerous hydrogen bonds involving unusual backbone
conformations and ribose 2'-hydroxyl groups. Overall, this work emphasizes
numerous features that account for the well-ordered structure of the whole
hairpin and highlights the loop properties that facilitate interaction with
antisense oligonucleotides.
PMID- 17041235
TI - MMASS: an optimized array-based method for assessing CpG island methylation.
AB - We describe an optimized microarray method for identifying genome-wide CpG island
methylation called microarray-based methylation assessment of single samples
(MMASS) which directly compares methylated to unmethylated sequences within a
single sample. To improve previous methods we used bioinformatic analysis to
predict an optimized combination of methylation-sensitive enzymes that had the
highest utility for CpG-island probes and different methods to produce
unmethylated representations of test DNA for more sensitive detection of
differential methylation by hybridization. Subtraction or methylation-dependent
digestion with McrBC was used with optimized (MMASS-v2) or previously described
(MMASS-v1, MMASS-sub) methylation-sensitive enzyme combinations and compared with
a published McrBC method. Comparison was performed using DNA from the cell line
HCT116. We show that the distribution of methylation microarray data is
inherently skewed and requires exogenous spiked controls for normalization and
that analysis of digestion of methylated and unmethylated control sequences
together with linear fit models of replicate data showed superior statistical
power for the MMASS-v2 method. Comparison with previous methylation data for
HCT116 and validation of CpG islands from PXMP4, SFRP2, DCC, RARB and TSEN2
confirmed the accuracy of MMASS-v2 results. The MMASS-v2 method offers improved
sensitivity and statistical power for high-throughput microarray identification
of differential methylation.
PMID- 17041236
TI - Association of -592C/A, -819C/T and -1082A/G interleukin-10 promoter
polymorphisms with idiopathic recurrent spontaneous abortion.
AB - Increasing evidence supports a role for altered T helper 1 (Th1)-Th2 cytokine
balance in idiopathic recurrent spontaneous abortion (RSA). The aim of this study
was to investigate the association of the interleukin 10 (IL-10) promoter
polymorphisms -592C/A, -819C/T and -1082A/G with RSA. Women (n = 350) with at
least three consecutive spontaneous abortions (RSA cases) and 200 control women
with at least two successful pregnancies were included. The frequency of the
819T allele [P = 0.05, odds ratio (OR) = 1.51], but not other single-nucleotide
polymorphisms (SNPs), was higher among RSA patients. Complete linkage
disequilibrium (LD) was seen between -592C and -819C and -1082G alleles, as well
as between -592A and -819T and between -819C and -1082G alleles only among
patients. Although the genotype frequencies (except for -819C/C) of the three
polymorphisms were comparable between patients and controls, higher frequency of
592A/-819T/-1082A haplotype (OR = 4.01, 95% CI = 1.83-7.95) was seen in cases
versus controls. Regression analysis indicated that, after adjusting for
potential variables, -592C/A (OR = 3.32, 95% CI = 1.76-6.27) and -819C/T (OR =
5.06, 95% CI = 2.59-9.91) were associated with exclusively early but not
exclusively late RSA, where negative association for both was noted. This
supports the notion of involvement of IL-10-592C/A and -819C/T polymorphisms as
inherited risk factors of idiopathic RSA.
PMID- 17041238
TI - The combination of ultrasound with antibiotics released from bone cement
decreases the viability of planktonic and biofilm bacteria: an in vitro study
with clinical strains.
AB - OBJECTIVES: Antibiotic-loaded bone cements are used for the permanent fixation of
joint prostheses. Antibiotic-loaded cements significantly decrease the incidence
of infection. The objective of this study was to investigate whether the
viability of bacteria derived from patients with a prosthesis-related infection
could be further decreased when antibiotic release from bone cements was combined
with application of pulsed ultrasound. METHODS: Escherichia coli ATCC 10798,
Staphylococcus aureus 7323, coagulase-negative staphylococci (CoNS 7368 and CoNS
7391) and Pseudomonas aeruginosa 5148 were grown planktonically in suspension and
as a biofilm on three different bone cements: Palacos R without gentamicin as
control, gentamicin-loaded Palacos R-G and gentamicin/clindamycin-loaded Copal.
The viability of planktonic and biofilm bacteria was measured in the absence and
presence of pulsed ultrasound for 40 h. RESULTS: Ultrasound itself did not affect
bacterial viability. However, application of pulsed ultrasound in combination
with antibiotic release by antibiotic-loaded bone cements yielded a reduction of
both planktonic and biofilm bacterial viability compared with antibiotic release
without application of ultrasound. CONCLUSIONS: This study shows that antibiotic
release in combination with ultrasound increases the antimicrobial efficacy
further than antibiotic release alone against a variety of clinical isolates.
Application of ultrasound in combination with antibiotic release in clinical
practice could therefore lead to better prevention or treatment of prosthesis
related infections.
PMID- 17041239
TI - Number of X-ray examinations performed on paediatric and geriatric patients
compared with adult patients.
AB - The age of the patient is of prime importance when assessing the radiological
risk to patients due to medical X-ray exposures and the total detriment to the
population due to radiodiagnostics. In order to take into account the age
specific radiosensitivity, three age groups are considered: children, adults and
the elderly. In this work, the relative number of examinations carried out on
paediatric and geriatric patients is established, compared with adult patients,
for radiodiagnostics as a whole, for dental and medical radiology, for 8
radiological modalities as well as for 40 types of X-ray examinations. The
relative numbers of X-ray examinations are determined based on the corresponding
age distributions of patients and that of the general population. Two broad
groups of X-ray examinations may be defined. Group A comprises conventional
radiography, fluoroscopy and computed tomography; for this group a paediatric
patient undergoes half the number of examinations as that of an adult, and a
geriatric patient undergoes 2.5 times more. Group B comprises angiography and
interventional procedures; for this group a paediatric patient undergoes a one
fourth of the number of examinations carried out on an adult, and a geriatric
patient undergoes five times more.
PMID- 17041240
TI - General guidelines for the assessment of internal dose from monitoring data:
progress of the IDEAS project.
AB - In recent major international intercomparison exercises on intake and internal
dose assessments from monitoring data, the results calculated by different
participants varied significantly. Based on this experience the need for
harmonisation of the procedures has been formulated within an EU 5th Framework
Programme research project. The aim of the project, IDEAS, is to develop general
guidelines for standardising assessments of intakes and internal doses. The IDEAS
project started in October 2001 and ended in June 2005. The project is closely
related to some goals of the work of Committee 2 of the ICRP and since 2003 there
has been close cooperation between the two groups. To ensure that the guidelines
are applicable to a wide range of practical situations, the first step was to
compile a database of well-documented cases of internal contamination. In
parallel, an improved version of an existing software package was developed and
distributed to the partners for further use. A large number of cases from the
database was evaluated independently by the partners and the results reviewed.
Based on these evaluations, guidelines were drafted and discussed with dosimetry
professionals from around the world by means of a virtual workshop on the
Internet early in 2004. The guidelines have been revised and refined on the basis
of the experiences and discussions in this virtual workshop. The general
philosophy of the Guidelines is presented here, focusing on the principles of
harmonisation, optimisation and proportionality. Finally, the proposed Levels of
Task to structure the approach of internal dose evaluation are reported.
PMID- 17041241
TI - Disruption of neurofascin localization reveals early changes preceding
demyelination and remyelination in multiple sclerosis.
AB - Saltatory conduction in the nervous system is enabled through the intimate
association between the leading edge of the myelin sheath and the axonal membrane
to demarcate the node of Ranvier. The 186 kDa neuron specific isoform of the
adhesion molecule neurofascin (Nfasc186) is required for the clustering of
voltage gated Na+ channels at the node, whilst the 155 kDa glial specific isoform
(Nfasc155) is required for the assembly of correct paranodal junctions. In order
to understand the relationship between these vital structures and how they are
affected in multiple sclerosis we have examined the expression of Nfasc155 and
Nfasc186 in areas of inflammation, demyelination and remyelination from post
mortem brains. Fourteen cases of neuropathologically confirmed multiple sclerosis
(8 female and 6 male; post-mortem delay 7-24 h; age 37-77 years; and disease
duration 15-40 years), comprising 20 tissue blocks with 32 demyelinating or
remyelinating lesions, were used in this study. A significant early alteration in
Nfasc155+ paranodal structures occurs within and adjacent to actively
demyelinating white matter lesions that are associated with damaged axons. Shaker
type Kv1.2 channels, normally located distally to the paranode, overlapped with
the disrupted Nfasc155+ structures. In the absence of Nfasc155, Kv1.2 channels
abutted normally clustered Nfasc186+ nodes, indicating that complete disruption
of the paranodal structure and movement of Kv1.2 channels precede alterations at
the node itself. Within areas of partial remyelination, a number of atypical
triple-Nfasc155+ structures were noted that may represent transient
oligodendrocyte-axonal contacts during the process of myelin repair or aberrant
interactions. Within shadow plaques discretely clustered Na+v, Nfasc186+ and
Nfasc155+ domains indicated the restoration of normal nodal architecture. The
alterations in oligodendrocyte Nfasc155 expression that accompany inflammation
and demyelination suggest an ongoing disruption to the axonal-oligodendrocyte
complex within newly forming as well as established lesions in multiple
sclerosis, resulting in destruction of the Nfasc186+/Na+v nodal complex vital to
successful fast neurotransmission in the CNS.
PMID- 17041242
TI - Mechanims of aerosol particle deposition in the Oro-pharynx under non-steady
airflow.
AB - Comparison of experimental and computational results of aerosol deposition in the
oro-pharyngeal cast of human published recently (Sosnowski TR, Moskal A, Gradon
L. (2006) Inhal Toxicol; 18: 773-780) demonstrated the applicability and
relevance of considering realistic breathing patterns in analysis of aerosol flow
and deposition within the human head airways. This issue is extended in the
current paper, focused on a detailed analysis of spatial and temporal
distribution of particle deposition in the oro-pharynx during inspiration. CFD
modeling was used to determine both the 3D airflow structure and the local
particle deposition fluxes at two different inspiratory patterns. Behavior of
aerosol (particle size: 0.3-10 micro m, material density: 2200 kg m(-3)) was
analyzed applying Lagrangian approach and considering Brownian effects for
submicron particles. Results indicate that particles of different sizes are
deposited in different parts of the oro-pharynx, depending on the point in the
inspiration cycle. Larger particles (3-10 micro m) are separated efficiently in
the naso-pharyngeal bend due to inertia, which predominate in the middle phase of
inspiration. Submicron particles are deposited more uniformly in the oro
pharyngeal space, and their separation from the air is enhanced in a short
transition period between inspiration and expiration. It suggests the importance
of mixing of inspired and expired air streams for particle deposition pattern.
Comparison of our computational results of deposition to the approximation
derived from the in vivo data (Stahlhofen W, Rudolf G, James AC. (1989) J Aerosol
Med; 2: 285-308) shows a good agreement for particles, for which the inertia is a
predominant mechanism of deposition. The results of this work lead to a more
detailed description of the dynamics of oro-pharyngeal aerosol deposition during
inspiratory part of the breathing cycle. The recognition of that problem is
essential for prediction of toxic or pharmacological local effects of inhaled
aerosols.
PMID- 17041243
TI - Nanotechnology: the next big thing, or much ado about nothing?
AB - Nanotechnology encompasses an increasingly sophisticated ability to manipulate
matter at the nanoscale, resulting in new materials, products and devices that
demonstrate new and unusual behaviour. While emerging nanotechnologies have great
potential for good, there are increasing concerns that the selfsame attributes
that make them attractive will also lead to new risks to human health. Research
to date suggests that some purposely made nanomaterials will present hazards
based on their structure--as well as their chemistry--thus challenging many
conventional approaches to risk assessment and management. People involved in
making and using these materials need to know what the risks are and how to
manage them, if safe nanotechnology-based businesses are to emerge. Yet the
challenges faced by the occupational hygiene community in ensuring safe nano
workplaces are substantial. We currently know enough to suggest that some
engineered nanomaterials will present new and unusual risks, but there is very
little information on how these risks can be identified, assessed and controlled.
And many nanomaterials are in production and use now. Good occupational hygiene
practices and existing knowledge on working with hazardous substances provide a
useful basis for working safely with nanomaterials. But where existing knowledge
fails, new research is needed to fill the gaps: this must be strategically
administered and targeted to addressing specific issues in a timely manner.
Failing to take these steps will ultimately lead to people's health being
endangered and emerging nanotechnologies floundering. However, with foresight,
sound science and strategic research, we have the opportunity to ensure that
emerging nanotechnologies are as safe as possible, while reaching their full
potential.
PMID- 17041244
TI - Comparison of the Grimm 1.108 and 1.109 portable aerosol spectrometer to the TSI
3321 aerodynamic particle sizer for dry particles.
AB - This study compared the response of two optical particle counters with that of an
aerodynamic particle sizer. The optical particle counters rely on the amount of
incident light scattered at 90 degrees by a particle to measure particle number
concentration by optical particle size. Two models of optical particle counters
from Grimm Technologies were used: the portable aerosol spectrometer (PAS) 1.108
(0.3-20 microm in 15 channels); and the PAS 1.109 (0.2-20 microm in 30 size
channels). With a substantially different operating principle from that employed
by the optical particle counters, the aerodynamic particle sizer (APS) model 3321
(TSI, Inc., St Paul, MN, USA) sizes particles according to their behavior in an
accelerating flow to provide particle number concentration by aerodynamic size
over a slightly narrower size range (0.5-20 microm) in 52 channels. The responses
of these instruments were compared for three sizes of monodisperse solid aerosols
composed of polystyrene latex spheres and a polydisperse aerosol composed of
Arizona test dust. The PASs provided similar results to those from the APS.
However, there were systematic differences among instruments in number and mass
concentration measurement that depended upon particle size.
PMID- 17041245
TI - Physical collection efficiency of filter materials for bacteria and viruses.
AB - The purpose of this study was to determine the physical collection efficiency of
commercially available filters for collecting airborne bacteria, viruses, and
other particles in the 10-900 nm (nanometer) size range. Laboratory experiments
with various polytetrafluoroethylene (PTFE), polycarbonate (PC) and gelatin
filters in conjunction with Button Inhalable samplers and three-piece cassettes
were undertaken. Both biological and non-biological test aerosols were used:
Bacillus atrophaeus, MS2, polystyrene latex (PSL), and sodium chloride (NaCl).
The B.atrophaeus endospores had an aerodynamic diameter of 900 nm, whereas MS2
virion particles ranged from 10 to 80 nm. Monodisperse 350 nm PSL particles were
used as this size was believed to have the lowest filtration efficiency. NaCl
solution (1% weight by volume) was used to create a polydisperse aerosol in the
10-600 nm range. The physical collection efficiency was determined by measuring
particle concentrations size-selectively upstream and downstream of the filters.
The PTFE and gelatin filters showed excellent collection efficiency (>93%) for
all of the test particles. The PC filters showed lower collection efficiency for
small particles especially <100 nm. Among the tested filters, the lowest
collection efficiencies, 49 and 22%, were observed for 1 and 3-microm pore size
PC filters at the particle sizes of 47 and 63 nm, respectively. The results
indicate that the effect of filter material is more significant for the size
range of single virions than for bacteria. The effect of filter loading was
examined by exposing filters to mixtures of PSL particles, which aimed at
mimicking typical indoor dust levels and size distributions. A 4-h loading did
not cause significant change in the physical collection efficiency of the tested
filters.
PMID- 17041246
TI - Annals of Occupational Hygiene at volume 50: many achievements, a few mistakes,
and an interesting future.
AB - The past 10 years have seen a doubling of the number of papers submitted to the
Annals, and a 5-fold increase in the number of institutions with access to the
journal. Electronic access is now far more important than print access. Papers
from British authors dominated the first 20 years of the journal, but the rest of
Europe is now more important, with Scandinavia and The Netherlands being the
major continental sources. North America is the other major source. For British
papers, there has been a big growth in government authors, and a decline in
papers from industry and armed forces. From many possible topics, trends are
selectively reviewed in: standards and exposure limits; measurement methods and
criteria; sampling strategy and statistics; fibres; control banding; dermal
exposure; and evaluation of control. For the future, we will continue to have the
same aims and standards, but the changes of the past few years, and the growth of
new approaches such as open access, have emphasized the difficulty of
forecasting. The growth in submissions from countries which we presently regard
as 'developing', and especially the growth in higher education in China, and the
amount of occupational disease there, are bound to have major impacts. Perhaps
the English language will not continue to dominate scientific publishing, but in
any case an eastward shift in the source of papers must lead to other changes.
PMID- 17041247
TI - Phospholipase C isoforms are localized at the cleavage furrow during cytokinesis.
AB - It has recently been demonstrated that phosphatidylinositol 4,5-bisphosphate
(PIP2) is localized at the cleavage furrow in dividing cells and its hydrolysis
is required for complete cytokinesis, suggesting a pivotal role of PIP2 in
cytokinesis. Here, we report that at least three mammalian isoforms of
phosphoinositide-specific phospholipase C (PLC), PLCdelta1, PLCdelta3 and
PLCbeta1, are localized to the cleavage furrow during cytokinesis. Targeting of
the delta1 isoform to the furrow depends on the specific interaction between the
PH domain and PIP2 in the plasma membrane. The necessity of active PLC in animal
cell cytokinesis was confirmed using the specific inhibitors for PIP2 hydrolysis.
These results support the model that activation of selected PLC isoforms at the
cleavage furrow controls progression of cytokinesis through regulation of PIP2
levels: induction of the cleavage furrow by a contractile ring consisting of
actomyosin is regulated by PIP2-dependent actin-binding proteins and formation of
specific lipid domains required for membrane separation is affected by
alterations in the lipid composition of the furrow.
PMID- 17041248
TI - Testing the theoretical framework of the COPE program for mothers of critically
ill children: an integrative model of young children's post-hospital adjustment
behaviors.
AB - OBJECTIVE: To test a theoretical model examining processes through which a parent
focused educational-behavioral intervention [Creating Opportunities for Parent
Empowerment (COPE)] relates to children's post-hospital adjustment problems.
METHODS: Mothers (n = 143) and their 2-7-year-old children, unexpectedly
hospitalized in two pediatric intensive care units, were randomized to COPE or
control conditions. Maternal measures included parental beliefs, anxiety,
negative mood, and child adjustment 3 months post discharge. Observers rated
maternal support of their children during hospitalization. RESULTS: Structural
equation modeling suggested that the model tested provided a reasonable fit to
the data [chi2 (97 df) = 129.43; p = .016; root mean square error of
approximation = .048; comparative fit index = .95]. COPE effects on children's
post-hospital externalizing behaviors were indirect, via associations with
parental beliefs and maternal negative mood state. Furthermore, COPE
participation was associated with more maternal support of their children, which
was also associated with less internalizing and externalizing behaviors 3 months
post discharge. CONCLUSION: Implementing COPE may help avert future mental health
problems in this high risk population. Understanding the processes by which an
already empirically validated program relates to child outcomes is likely to aid
clinicians and administrators in the widespread uptake of the COPE program.
PMID- 17041249
TI - The MDRD formula and validation.
PMID- 17041251
TI - Genetic variability affects the development of brown adipocytes in white fat but
not in interscapular brown fat.
AB - Cold exposure induces brown adipocytes in retroperitoneal fat (RP) of adult A/J
mice but not in C57BL/6J (B6) mice. In contrast, induction of the mitochondrial
uncoupling protein 1 gene (Ucp1) in interscapular brown adipose tissue (iBAT)
shows no strain dependence. We now show that unlike iBAT, in which Ucp1 was
expressed in the fetus and continued throughout life, in RP, Ucp1 was transiently
expressed between 10 and 30 days of age and then disappeared. Similar to the lack
of genetic variation in the expression of Ucp1 in iBAT during cold induction of
adult mice, no genetic variation in Ucp1 expression in iBAT was detected during
development. In contrast, UCP1-positive multilocular adipocytes, together with
corresponding increases in Ucp1 expression, appeared in RP at 10 days of age in
A/J and B6 mice, but with much higher expression in A/J mice. At 20 days of age,
brown adipocytes represent the major adipocyte present in RP of A/J mice. The
disappearance of brown adipocytes by 30 days of age suggested that tissue
remodeling occurred in RP. Genetic variability in Ucp1 expression could not be
explained by variation in the expression of selective transcription factors and
signaling molecules of adipogenesis. In summary, the existence of genetic
variability between A/J and B6 mice during the development of brown adipocyte
expression in RP, but not in iBAT, suggests that developmental mechanisms for the
brown adipocyte differentiation program are different in these adipose tissues.
PMID- 17041252
TI - Falls and patient safety for older adults.
AB - The risk of falling increases with age. Falls in the elderly have been found to
raise mortality and morbidity rates and are a leading cause of premature
admission to long-term care facilities. Attention to known intrinsic and
extrinsic factors that predispose to falling is important in community dwelling
and institutionalized older adults. New government guidelines for long-term care
facilities have helped focus attention on the safety aspect of fall risk and
information about the physical and psychological impact of falling is increasing.
Implementation of fall prevention protocols, including the use of fall risk
assessment tools, may help reduce the incidence of falls and resultant
complications.
PMID- 17041250
TI - The natural inverse agonist agouti-related protein induces arrestin-mediated
endocytosis of melanocortin-3 and -4 receptors.
AB - Agouti-related protein (Agrp), one of the two naturally occurring inverse
agonists known to inhibit G protein-coupled receptor activity, regulates energy
expenditure by decreasing basal and blocking agonist-promoted melanocortin
receptor (MCR) signaling. Here we report that, in addition to its inverse
agonistic activities, Agrp exhibits agonistic properties on the endocytosis
pathway of melanocortin receptors. Sustained exposure of human embryonic kidney
293 cells to Agrp induced endocytosis of the MC3R or the MC4R. The extent and
kinetics of Agrp-promoted MCR endocytosis were similar to the endocytosis induced
by melanocortins. Using the bioluminescence resonance energy transfer technique,
we further showed that after binding of Agrp both MCRs interacted with beta
arrestins. In line with this observation, in COS-7 cells co-expression of beta
arrestins enhanced Agrp-induced MCR endocytosis, whereas in human embryonic
kidney 293 cells co-transfection of beta-arrestin-specific small interference
RNAs diminished Agrp-promoted endocytosis. This new regulatory mechanism was
likewise detectable in a cell line derived from murine hypothalamic neurons
endogenously expressing MC4R, pointing to the physiological relevance of Agrp
promoted receptor endocytosis. In conclusion, we demonstrated that Agrp does not
solely act by directly blocking MCR signaling but also by reducing the amount of
MCR molecules accessible to melanocortins at the cell surface. This beta-arrestin
dependent mechanism reveals a new aspect of MCR signaling in particular and
refines the concept of G protein-coupled receptor antagonism in general.
PMID- 17041253
TI - Obesity: changing the face of geriatric care.
AB - Statistics suggest that more and more older Americans are carrying extra weight
an estimated 40% of individuals between the ages of 60 and 69 have a body mass
index >30 and 30% of persons between ages of 70 and 79 years are obese. Obesity,
coupled with the challenges of aging, leads to an unfortunate burden of chronic
disease, functional decline, poor quality of life, and an increased risk of being
homebound. Physical assessment of the elderly obese patient should include
measurement of height, weight (to determine body mass index) and waist
circumference (to address central obesity) and consideration of vascular, skin,
and mobility issues. Weight management strategies such as diet and hydration
should balance nutritional requirements with weight loss; particular attention to
protein needs in chair- and bedbound patients is necessary. Additional approaches
such as exercise, bariatric weight loss surgery, and weight loss medication
should be considered on an individual basis related to their inherent risks in
this population. Weight loss/management options framed from an interdisciplinary
perspective can improve quality of life for these patients and their caregivers.
Research specific to obesity in this age group is warranted.
PMID- 17041254
TI - Lower extremity malignancies masquerading as ulcers.
AB - Ulcers of the lower extremities, particularly in individuals >65 years old, are a
common cause for visits to the podiatrist, wound care specialist, primary care
physician, vascular surgeon, or dermatologist. When an ulcer does not respond to
adequate medical and wound care, the potential for an underlying malignancy
should be considered. Cutaneous malignancies that may masquerade as ulcers
include nodulo-ulcerative basal cell carcinoma, squamous cell carcinoma,
keratoacanthoma, nodular melanoma, tumor stage mycosis fungoides, lymphomatoid
granulomatosis, lymphomatoid papulosis, angiosarcoma, and cutaneous metastases
from internal malignancy. It is crucial for healthcare providers to recognize
these presentations and render appropriate therapeutic intervention.
PMID- 17041255
TI - Nutrition and aging: a transdisciplinary approach.
AB - Numerous factors may predispose the elderly to decreased nutritional status.
These include physical (illness, physiological changes related to aging, pain,
and gastro-intestinal issues), psychological (depression), and socio-economic
(income and decreased mobility that leads to isolation and loneliness). The
latter may affect food insecurity and the ability to nourish and hydrate. When
nutrition suffers, wellness and healing cannot be sustained. Healthcare providers
should 1) be aware of the care implications associated with decreased nutritional
status, 2) assess nutritional status, and 3) individualize treatment plans,
providing and/or pursuing assistance for persons at risk for nutritional
deficiency by interceding with commercially prepared products, medications, and
supplements and securing consultations with dietitians. A transdisciplinary team
approach (multidisciplinary across specialties and settings) can provide the
needed care.
PMID- 17041256
TI - Combinatorial protein design strategies using computational methods.
AB - Computational methods continue to facilitate efforts in protein design. Most of
this work has focused on searching sequence space to identify one or a few
sequences compatible with a given structure and functionality. Probabilistic
computational methods provide information regarding the range of amino acid
variability permitted by desired functional and structural constraints. Such
methods may be used to guide the construction of both individual sequences and
combinatorial libraries of proteins.
PMID- 17041257
TI - Global incorporation of unnatural amino acids in Escherichia coli.
AB - The incorporation of amino acid analogs is becoming increasingly useful. Site
specific incorporation of unnatural amino acids allows the application of
chemical biology to protein-specific investigations and applications. However,
the global incorporation of unnatural amino acids allows for tests of proteomic
and genetic code hypotheses. For example, the adaptation of organisms to
unnatural amino acids may lead to new genetic codes. To understand and quantify
changes from such perturbations, an understanding is required of the
microbiological and proteomic responses to the incorporation of unnatural amino
acids. Here we describe protocols to characterize the effects of such proteome
wide perturbations.
PMID- 17041258
TI - Considerations in the design and optimization of coiled coil structures.
AB - Coiled coil motifs are, despite their apparent simplicity, highly specific, and
play a significant role in the understanding of tertiary structure and its
formation. The most commonly observed of the coiled coils, the parallel dimeric,
is yet to be fully characterized for this structural class in general.
Nonetheless, strict rules have emerged for the necessity of specific types of
amino acids at specific positions. In this chapter, we discuss this system in
light of existing coiled coil structures and in applying rules to coiled coils
that are to be designed or optimized. Understanding and expanding on these rules
is crucial in using these motifs, which play key roles in virtually every
cellular process, to act as drug-delivery agents by sequestering other proteins
that are not behaving natively or that have been upregulated (for example, by
binding to coiled coil domains implicated in oncogenesis). The roles of the a and
d "hydrophobic" core positions and the e and g "electrostatic" edge positions in
directing oligomerization and pairing specificity are discussed. Also discussed
is the role of these positions in concert with the b, c, and f positions in
maintaining alpha-helical propensity, helix solubility, and dimer stability.
PMID- 17041259
TI - Calcium indicators based on calmodulin-fluorescent protein fusions.
AB - Calmodulin (CaM) is an ubiquitous protein involved in Ca2+-mediated signal
transduction. On Ca2+ influx, CaM acquires a strong affinity to various cellular
proteins with one or more CaM recognition sequences, resulting in the onset or
termination of Ca2+-regulated cascades. Through nuclear magnetic resonance and
crystallographic structural studies of these Ca2+-CaM complexes, we have gained a
deep understanding of CaM target recognition mechanisms. One immediate
application is the creation of protein-based Ca2+ sensors using CaM complexes and
green fluorescent proteins, previously named "chameleon." The major advantage of
chameleons is that they can be expressed in single cells and targeted to the
specific organelles or tissues to measure localized Ca2+ changes. This chapter
describes the methods involved in cloning chameleons, characterizing their
biochemical and biophysical properties, and imaging them in single cells using a
digital fluorescence microscope.
PMID- 17041260
TI - Design and synthesis of artificial zinc finger proteins.
AB - Of the DNA-binding motifs, the (Cys)2(His)2-type zinc finger motif has great
potential for manipulation. The zinc finger motif offers an attractive framework
for the design of novel DNA-binding proteins. Specially, a structure-based design
strategy is valuable for the creation of new artificial zinc finger proteins that
have novel DNA-binding properties, namely, long-DNA recognition, DNA bending, and
AT-rich sequence recognition. Herein, new strategies for the design of multi-zinc
finger proteins for the recognition of a target DNA sequence, a DNA-bending zinc
finger protein, a (His)4-type zinc finger protein, and an AT-recognizing zinc
finger protein are described based on recent experimental results.
PMID- 17041261
TI - Monobodies: antibody mimics based on the scaffold of the fibronectin type III
domain.
AB - We developed the use of the 10th fibronectin type III domain of human fibronectin
(FNfn10) as a scaffold to display multiple surface loops for target binding. We
termed FNfn10 variants with novel binding function "monobodies." FNfn10 is a
small (94 residues) protein with a beta-sandwich structure similar to the
immunoglobulin fold. It is highly stable without disulfide bonds or metal ions,
and it can be expressed in the correctly folded form at a high level in bacteria.
These desirable physical properties render the FNfn10 scaffold compatible with
virtually any display technologies. This chapter describes methods for library
construction and screening and for the production of monobodies.
PMID- 17041263
TI - Protein library design and screening: working out the probabilities.
AB - In designing protein libraries for selection, we must coordinate our capacity to
create a large diversity of protein variants with the physical limitations of
what we can actually screen. This chapter aims to bring the language of
probabilities into the protein engineer's laboratory to answer some of our common
questions: How can we most efficiently design a library? What fraction of the
theoretical library diversity have we actually sampled at the end of the day?
What is the probability of missing an individual of the library? Are the
mutations present in the variants we have selected statistically meaningful or
the product of random variation? The computation of these criteria throughout the
process of experimental protein engineering will enable us to better design and
evaluate the products of our libraries of protein variants.
PMID- 17041262
TI - Engineering site-specific endonucleases.
AB - Site-specific endonucleases are involved in many aspects of the biochemistry of
nucleic acids. Restriction enzymes and their relatives have become paradigms for
enzymes acting on DNA. Numerous efforts have been devoted to changing their
specificity by rational protein design, with, by and large, little success,
presumably because the recognition process is highly redundant and recognition
and catalysis are tightly coupled. This chapter describes one of the few
successful examples of a change in specificity--namely the conversion of the
mismatch repair nuclease, MutH, which, when stimulated by MutS and MutL, nicks
hemimethylated d(GATC) sites, into a variant that cleaves fully methylated DNA as
well as hemimethylated and unmethylated DNA. This chapter will describe the
various steps involved in this design project, starting from the analysis of the
structure and the identification of candidate amino acid residues responsible for
sensing the methylation status, to the generation and characterization of MutH
variants with an altered specificity toward hemimethylated d(GATC) sites.
PMID- 17041264
TI - Protein design by binary patterning of polar and nonpolar amino acids.
AB - The design of large libraries of well-folded de novo proteins is a powerful
approach toward the ultimate goal of producing proteins with novel structures and
functions for use in industry or medicine. A method for library design that
incorporates both rational design and combinatorial diversity relies on the
"binary patterning" of polar and nonpolar amino acids. Binary patterning is based
on the premise that the appropriate arrangement of polar and nonpolar residues
can direct a polypeptide chain to fold into amphipathic elements of secondary
structure that anneal together to form a desired tertiary structure. A designed
binary pattern exploits the periodicities inherent in protein secondary
structure, and allows the identity of the side chain at each polar and nonpolar
position to be varied combinatorially. This chapter provides an overview of the
considerations necessary to use binary patterning to design libraries of novel
proteins.
PMID- 17041265
TI - Versatile DNA fragmentation and directed evolution with nucleotide exchange and
excision technology.
AB - Mimicking natural evolution by DNA shuffling is a commonly used method for the
optimization of DNA and protein properties. Here, we present an advancement of
this approach whereby a gene library is amplified using a standard polymerase
chain reaction (PCR), but incorporates dUTP as a fragmentation-defining exchange
nucleotide, together with the four standard dNTPs. Incorporated uracil bases are
excised using uracil-DNA-glycosylase, and the DNA backbone subsequently is
cleaved with piperidine. This oligonucleotide pool is then reassembled with an
internal primer extension procedure using a proofreading polymerase to increase
yield, and, finally, is amplified by PCR. Denaturing polyacrylamide urea gels
demonstrate this method to produce adjustable fragmentation size ranges dependent
on the dUTP:dTTP ratios. Using the model protein, chloramphenicol
acetyltransferase I, the sequencing of shuffled gene libraries based on a PCR
containing 33% dUTP revealed a low mutation rate, of approx 0.1%, with an average
parental fragments size of 86 bases, even without the use of a fragment-size
separation. Nucleotide exchange and excision technology (NExT) DNA shuffling is,
thus, reproducible and easily executed, making it superior to competing
techniques. Additionally, NExT fragmentation outcome can be predicted using the
computer software, NExTProg.
PMID- 17041266
TI - Degenerate oligonucleotide gene shuffling.
AB - Improvement of the biochemical characteristics of enzymes has been aided by
misincorporation mutagenesis and DNA shuffling. Shuffling techniques can be used
on a collection of mutants of the same gene, or related families of genes can be
shuffled to produce mutants encoding chimeric gene products. One difficulty with
current shuffling procedures is the predominance of unshuffled ("parental")
molecules in the pool of mutants. We describe a procedure for gene shuffling
using degenerate primers that allows control of the relative levels of
recombination between the genes that are shuffled and reduces the regeneration of
unshuffled parental genes. This procedure has the advantage of avoiding the use
of endonucleases for gene fragmentation before shuffling and allows the use of
random mutagenesis of selected segments of the gene as part of the procedure. We
illustrate the use of the technique with a diverse family of beta-xylanase genes
that possess widely different G and C contents.
PMID- 17041267
TI - M13 bacteriophage coat proteins engineered for improved phage display.
AB - This chapter describes a method for increasing levels of protein fusions
displayed on the surfaces of M13 bacteriophage particles. By introducing
mutations into the anchoring M13 coat protein, protein display levels can be
increased by up to two orders of magnitude. Experimental methods are presented
for the design, construction, and screening of phage-displayed libraries for
improved protein display.
PMID- 17041268
TI - Ribosome-inactivation display system.
AB - We present a novel strategy for the connection of phenotype and genotype in vitro
that can be used for the selection of functional proteins. The strategy involves
the generation of a stable complex among a ribosome, an messenger RNA and its
translated protein, without removal of the termination codon, as a result of the
action of the ricin A chain during translation. The technique requires no
transfection, no chemical synthesis, no ligation, and no removal of the
termination codon. Thus, our novel ribosome-inactivation display system should
provide, without loss of the pool population, a reliable, simple, and robust
selection system for the in vitro evolution of the properties of proteins in a
predictable direction by a combination of randomization and appropriate selection
strategies.
PMID- 17041269
TI - Compartmentalized self-replication: a novel method for the directed evolution of
polymerases and other enzymes.
AB - Compartmentalized self-replication (CSR) is a novel method for the directed
evolution of enzymes and, in particular, polymerases. In its simplest form, CSR
consists of a simple feedback loop involving a polymerase that replicates only
its own encoding gene (self-replication). Self-replication occurs in discrete,
spatially separate, noncommunicating compartments formed by a heat-stable water
in-oil emulsion. Compartmentalization ensures the linkage of phenotype and
genotype (i.e., it ensures that each polymerase replicates only its own encoding
gene to the exclusion of those in the other compartments). As a result, adaptive
gains by the polymerase directly (and proportionally) translate into genetic
amplification of the encoding polymerase gene. CSR has proven to be a useful
strategy for the directed evolution of polymerases directly from diverse
repertoires of polymerase genes. In this chapter, we describe some of the CSR
protocols used successfully to evolve variants of T. aquaticus Pol I (Taq)
polymerase with novel and useful properties, such as increased thermostability or
resistance to the potent inhibitor, heparin, from a repertoire of randomly
mutated Taq polymerase genes.
PMID- 17041270
TI - Synthesis of degenerated libraries of the ras-binding domain of raf and rapid
selection of fast-folding and stable clones with the dihydrofolate reductase
protein fragment complementation assay.
AB - The protein-engineering field is mainly concerned with the design of novel enzyme
activities or folds and with understanding the fundamental sequence determinants
of protein folding and stability. Much effort has been put into the design of
methods to generate and screen libraries of polypeptides. Screening for the
ability of proteins to bind with high affinity and/or specificity is most often
approached with phage display technologies. In this chapter, we present an
alternative to phage display, performed totally in vivo, based on the
dihydrofolate reductase (DHFR) protein-fragment complementation assay (PCA). We
describe the application of the DHFR PCA to the selection of degenerated
sequences of the ras-binding domain (RBD) of raf for correct folding and binding
to ras. Our screening system allows for enrichment of the libraries for the best
behaving sequences through iterative competition experiments, without the
discrete library screening and expansion steps that are necessary in in vitro
approaches. Moreover, the selected clones can be processed rapidly to
purification by Ni-nitrilotriacetic acid (NTA) affinity chromatography in 96-well
plates. Our methods are particularly suitable for the designing and screening of
libraries aimed at studying sequence folding and binding determinants. Finally,
it can be adapted for library-against-library screening, thus, allowing for
coevolution of interacting proteins simultaneously.
PMID- 17041271
TI - A general method of terminal truncation, evolution, and re-elongation to generate
enzymes of enhanced stability.
AB - Improving enzyme stability is a highly desirable design step in generating
enzymes able to function under extreme conditions, such as elevated temperatures,
while having the additional benefit of being less susceptible to cleavage by
proteases. For these reasons, many different approaches and techniques have been
devised in constructing such proteins, but the results to date have been of mixed
success. Here, we present a robust method involving the terminal truncation,
random mutagenesis and fragmentation, recombination, elongation, and finally,
selection at physiological temperatures, to generate an enzyme with improved
stability. Three cycles of directed evolution comprising of random mutagenesis,
DNA shuffling, and selection at 37 degrees C were used, using the bacterial
enzyme TEM-1 beta-lactamase as a model protein to yield deletion mutants with in
vivo ampicillin resistance levels comparable to wild-type (wt) enzyme. Kinetic
studies demonstrate the selected mutant to have a significantly improved
thermostability relative to its wt counterpart. Elongation of this mutant to the
full-length gene resulted in a beta-lactamase variant with dramatically increased
thermostability. This technique was so fruitful that the evolved enzyme retained
its maximum catalytic activity even 20 degrees C above its wt parent protein
optimum. Thus, structural perturbation by terminal truncation and subsequent
compensation by directed evolution at physiological temperatures is a fast,
efficient, and highly effective way to improve the thermostability of proteins
without the need for selecting at elevated temperatures.
PMID- 17041272
TI - Iron deficiency in infancy and mother-child interaction at 5 years.
AB - Five-year-old Costa Rican children, who had either chronic, severe iron
deficiency or good iron status in infancy, were observed with their mothers
during a structured interaction task in a laboratory setting and everyday
interactions in their home. Child affect and behavior as well as the quality of
mother-child interaction of the formerly chronic iron-deficient children (n = 40)
were compared to those with good iron status in infancy (n = 102). Children who
had chronic iron deficiency in infancy were more likely to display lower levels
of physical activity, positive affect, and verbalization during the structured
task at 5 years, despite iron therapy that corrected their iron deficiency anemia
in infancy. Mother-child reciprocity during the structured task (e.g., eye
contact, shared positive affect, turn taking) was more likely to be lower in the
chronic iron deficiency group compared to the good iron group. Mothers of
children in the chronic iron deficiency group showed less responsivity in both
settings. These results show that children with chronic, severe iron deficiency
in infancy continue at behavioral disadvantage relative to their peers at school
entry. Sustained differences in mother-child interaction might contribute to the
long-lasting behavioral and developmental alterations reported in children with
chronic, severe iron deficiency in infancy.
PMID- 17041273
TI - Characteristics of school-age children with autism.
AB - The objectives of this study were to provide a national profile of children with
autism, to describe the impact of autism on school functioning, and to describe
the utilization of services among children with autism. We performed a cross
sectional descriptive analysis of 9583 children (grades K-8) from the 2001
National Household Education Survey Before and After School Survey. We used
parent-reported information to determine the prevalence of autism, and children
with autism were compared to children without autism on sociodemographic measures
and several measures of school functioning and utilization of services. The
prevalence of autism in this sample was 66 per 10,000. Children with autism were
proportionately represented in all communities and all regions of the country.
While children with autism were equally likely to attend public schools compared
to children without autism, they were significantly more likely to have learning
difficulties and to carry multiple diagnoses, including attention deficit
disorder and learning disability. Most of these children received services for
their disability through the school district. In conclusion, data from this
survey yielded a prevalence estimate of autism similar to other recent studies.
Children with autism have performance and behavior problems that persist despite
the availability of services to the majority of children. The important needs of
these children warrant further attention.
PMID- 17041275
TI - Physical health of mothers with HIV/AIDS and the mental health of their children.
AB - A longitudinal study was conducted on the psychological well-being of 81 young
children (mean age = 8.8 years) living with mothers with AIDS or HIV-infected
mothers with symptomatic disease. The relationship between mothers' physical
health and children's psychological well-being was investigated. The children
were assessed at seven time points over approximately 6 years. Individual growth
models were estimated for children's depression, anxiety, and aggressiveness in
relation to: mothers' viral load (medical records) and physical functioning,
number of HIV-related physical symptoms, and medical visits due to illness (self
report). Results showed significant linear declines in children's depression,
anxiety, and aggressiveness over time. Lower levels of physical functioning and
more physical symptoms among mothers were associated with higher levels of
children's depression, anxiety, and aggressiveness at baseline. Lower levels of
physical functioning and more physical symptoms among mothers were associated
with initially high but more rapidly decreasing levels of depression among
children. However, mothers who began the study in better health appear to have
changed in health more quickly than mothers who began the study in poorer health.
Thus, stability in mothers' health appears to be associated with a more rapid
improvement in children's mental health over time. Our findings suggest that the
measures representing observable levels of, and changes in, mothers' health that
are most likely to be directly experienced by themselves and their children are
the measures that are most predictive of changes in children's mental health over
time.
PMID- 17041276
TI - Predictors of stress in parents of children with fetal alcohol spectrum
disorders.
AB - This study examined child characteristics and family factors as predictors of
stress in the biological or adoptive parents of 6- to 12-year-old children with
fetal alcohol spectrum disorders (FASDs). Impaired executive functioning, poorer
adaptive functioning, externalizing and internalizing behavior problems, and
adoptive parent status all made significant and independent contributions to the
prediction of higher levels of child domain stress, as reported by parents on the
Parenting Stress Index. Biological parent status and fewer family resources were
associated with higher levels of parent domain stress. Teacher ratings of the
child"s executive functioning impairments and externalizing and internalizing
behavior problems also were associated with parent reports of child domain
stress. Findings highlight the need to provide support not only to children with
FASDs, but to their caregivers as well.
PMID- 17041277
TI - 11 Month-old twins with food avoidance.
PMID- 17041279
TI - ADHD: new pharmacological treatments on the horizon.
AB - Attention-deficit/hyperactivity disorder (ADHD) is the most common
neurobehavioral disorder affecting school-age children. In many cases, symptoms
persist into adolescence and adulthood, causing significant lifelong impairments
in academic, career, and social functioning. The stimulants methylphenidate and
amphetamines have been used for decades as first-line therapy for the treatment
of ADHD. Short-acting stimulant formulations control symptoms only for a few
hours, creating the need for multiple daily doses of the medication. For school
age children, this necessitates administering medication during school hours,
creating the potential for embarrassment and noncompliance. To offset these
problems, longer acting stimulant formulations have been developed. Long-acting
medications often control symptoms for up to 8 hours with only one daily dose of
the medication, eliminating the need for in-school administration. Some long
acting stimulants are designed to control symptoms for up to 10 to 12 hours.
Although stimulants are effective in most cases, some children are unable to
tolerate these medications. Nonstimulant options are available for the treatment
of ADHD and include atomoxetine, alpha-adrenergic agents, and antidepressants. Of
these, atomoxetine is the only medication approved to treat ADHD. In spite of the
number of medications available for the management of ADHD, treatment options
with greater flexibility and reduced side effects are still desirable. A
transdermal methylphenidate patch has recently been approved, and advances to
existing stimulants currently under development include an amphetamine prodrug
and a longer acting formulation of amphetamine. In addition, a number of
nonstimulant entities, including guanfacine and modafinil, are under development
for the treatment of ADHD.
PMID- 17041282
TI - Female monozygotic twins with selective mutism--a case report.
PMID- 17041283
TI - Mental health and health-related quality of life: a 10-year follow-up of tortured
refugees.
AB - The aim of the study was to identify predictors of mental symptoms (posttraumatic
stress disorder, depression, and anxiety), and of health-related quality of life
in refugees 10 years after referral to the Rehabilitation and Research Centre for
Torture Victims, and to study changes in mental health over time. The study
sample comprises 139 tortured refugees admitted to a pretreatment assessment in
1991 to 1994. Data on background and trauma, and in a subsample on mental
symptoms, were collected at baseline. In 2002 and 2003, data on mental symptoms,
health-related quality of life, and the participants' social situation were
collected. The level of emotional distress was high at follow-up. Social
relations and unemployment at follow-up were important predictors of mental
health symptoms and low health-related quality of life. A significant decrease in
mental symptoms was observed in the subsample. Social relations and unemployment
should be taken into account when developing health-related and social
interventions.
PMID- 17041284
TI - Predicting medication-free treatment response in acute psychosis: cross
validation from the Finnish Need-Adapted Project.
AB - This study tested predictors of 2-year antipsychotic-free response from the
Soteria study (older, better social functioning, fewer cardinal symptoms) using
data from the Finnish Acute Psychosis Integrated treatment study. The quasi
experimental study compared need-adapted family-oriented psychosocial
intervention within a 3-week antipsychotic-free trial to psychosocial
intervention plus antipsychotic medications. Forty-six percent of experimental
completers (37% of intent-to-treat subjects) were successfully treated without
antipsychotic medications for the entire 2-year study. The DSM-III-R diagnoses of
schizophrenia and schizophreniform disorder and Soteria-suggested predictors were
not related to antipsychotic-free response. Different variables within the same
domains of good prognosis and fewer schizophrenia symptoms predicted
antipsychotic-free response or nonresponse with 74% accuracy. The 6-month
duration of symptom criterion distinguishing schizophrenia from schizophreniform
disorder does not separate medication-free treatment responders from those
requiring medications. Prognosis appears related to antipsychotic-free response
and may be helpful in distinguishing schizophrenia from schizophreniform disorder
in early episodes.
PMID- 17041285
TI - Insight and recovery from acute psychotic episodes: the effects of cognitive
behavior therapy and premature termination of treatment.
AB - Research suggests that insight in schizophrenia is only weakly responsive to
targeted psychosocial interventions. One of the aims of the present study was to
examine the effects on insight of cognitive behavior therapy (CBT) for acutely
psychotic patients. A second aim was to test predictions drawn from research on
recovery styles that patients who reject psychological assistance will show a
reduction in insight while those who continue to accept psychological assistance
will show increases in insight over time. Patients with acute schizophrenia
spectrum disorders were assigned at random to treatment-as-usual (TAU) or TAU
plus CBT. The latter were also divided into those who terminated treatment
prematurely (dropouts) and those who did not (stay-ins). Insight was assessed at
baseline and three follow-up assessments. Insight increased over the follow-up
period, but there were no differences between the CBT and TAU groups. Within the
CBT group, dropouts showed a reduction in insight at the 6-month assessment
before returning to their baseline level, while the stay-ins showed linear
improvement up to 12 months. Possible explanations for these contrasting
patterns, in terms of resilience, attachment styles, and an insecure sense of
self, are discussed.
PMID- 17041286
TI - Adherence to medication and quality of life in people with schizophrenia: results
of a European multicenter study.
AB - Quality of life is often severely impaired in people with schizophrenia, and
adherence to antipsychotic medication has been consistently found to be low in
this population. Although there is a considerable amount of evidence on these two
variables in schizophrenia research, there is only limited knowledge on how they
relate to one another. The aim of this study is to develop a meaningful model of
the relationship between quality of life and adherence that includes mediating
variables. A multicenter randomized controlled trial recruited 409 subjects in
London, Verona, Amsterdam, and Leipzig. Baseline interviews obtained data on
adherence, quality of life, and other variables. We used graphical modeling to
investigate the relationships between the variables. No direct relation could be
discerned between subjective quality of life and adherence to medication.
Mediating variables, most importantly symptomatic impairment, global functioning,
and medication side effects, were identified by the model. It can be concluded
that, when aiming at the improvement of quality of life in people with
schizophrenia, variables other than adherence, i.e., symptomatic impairment,
global functioning, and medication side effects, should be targeted.
PMID- 17041287
TI - Naive theory impairment in schizophrenia: is it domain-specific?
AB - The ability to represent mental states of self and others to account for behavior
is called theory of mind (ToM). This study examined whether ToM deficit in
schizophrenia patients is a specific deficit in the cognitive component of
interpersonal skills or a more global deficit, involving impaired information
processing skills. Schizophrenia inpatients (N = 41) were compared with a control
group of healthy subjects (N = 22) and to nonschizophrenia psychiatric patients
(24 with affective disorders, seven with other psychosis) over a range of ToM
tasks and another naive theory (theory of biology; ToB). Psychiatric inpatients
as a whole showed significant deficit compared with the control group of healthy
subjects in ToM tasks. The schizophrenia patients showed significantly larger
deficits compared with patients suffering from affective disorder, while the
performance of patients with nonschizophrenia psychosis was intermediate. In
contrast, no difference was observed in the performance of the different groups
on the ToB tasks. The fact that a deficit was found in ToM but not in ToB
suggests a specific deficit in a cognitive component of interpersonal skills in
schizophrenia rather than a general deficit in information processing skills.
Naive theories deficits in schizophrenia seem to be domain-dependent.
PMID- 17041288
TI - Jumping to conclusions and delusion proneness: the impact of emotionally salient
stimuli.
AB - The present study investigated whether those who are delusion-prone demonstrate a
jumping to conclusions reasoning bias similar to that demonstrated by those with
active delusions in previous studies. Two hundred individuals, none of whom had a
psychotic disorder, were assessed for delusion-proneness and engaged in two
probabilistic reasoning tasks, one emotionally neutral and the other emotionally
salient. The emotionally salient task consisted of both positively and negatively
valenced personally referent stimuli. Level of delusion-proneness was positively
related to jumping to conclusions when stimuli were emotionally salient, though
the bias was present only when the first personally referent stimulus was
negatively valenced (p < 0.01). Thus, the jumping to conclusions reasoning bias
previously demonstrated by individuals who have active delusions appears to be
demonstrated under certain conditions by those who are not actively delusional
but score high on a measure of delusion-proneness.
PMID- 17041289
TI - Self-stigma in women with borderline personality disorder and women with social
phobia.
AB - Little is known about how women with borderline personality disorder (BPD) and
women with social phobia react to mental illness stigma. The goal of this study
was to assess empirically self-stigma and its correlates in these groups. Self
stigma and related constructs were measured by self-report questionnaires among
60 women with BPD and 30 women with social phobia. Self-stigma was inversely
related to self-esteem, self-efficacy, and quality of life and predicted low self
esteem after controlling for depression and shame-proneness. Stereotype awareness
was not significantly correlated with self-esteem or quality of life. While there
was no difference in stereotype awareness between women with BPD and women with
social phobia, women with BPD showed higher self-stigma than women with social
phobia. Self-stigma is associated with low self-esteem and other indices of poor
psychological well-being. In comparison to women with social phobia, women with
BPD suffer from more self-stigma. This may reflect intense labeling processes as
being mentally ill due to repeated hospitalizations, frequent interpersonal
difficulties, and visible scars.
PMID- 17041290
TI - A valence-dependent group-specific recall bias of retrospective self-reports: a
study of borderline personality disorder in everyday life.
AB - Recall is an active reconstruction process likely to distort past experiences.
This distortion, known as recall bias, seems to manifest itself differently in
sick and healthy people. A recall bias has been documented in several disorders,
but never investigated in borderline personality disorder (BPD). To determine
recall bias in BPD, we assessed momentary and retrospective ratings of specific
emotions in 50 patients with BPD and 50 healthy controls (HCs), using the
methodology of 24-hour ambulatory monitoring. Our data reveal a group-specific
valence-dependent recall bias of retrospective self-report, indicated by a
different overall recall pattern in HCs and BPD. BPD patients show an overall
negative recall pattern, whereas HCs show a positive recall pattern. A
traditional questionnaire approach does not distinguish between symptoms of the
disorder and recall bias, although the pathological mechanisms underlying them as
well as the appropriate treatment strategies may be different.
PMID- 17041291
TI - Specificity of patients' satisfaction with the delivery and outcome of treatment.
AB - This study investigated the hypotheses that the general disposition to be
satisfied is more influential than the nature of service delivery in determining
satisfaction with treatment, and that there is a specificity to satisfaction with
the delivery of care and with clinical outcome of care that makes their ratings
distinct. Data were obtained by questionnaire at intake into treatment and 4
months later from 154 male veterans. There were statistically significant
relationships between the general disposition to be satisfied and satisfaction
with treatment, but they had only a trivial effect on the relationships between
treatment satisfaction and other variables. There was, however, a specificity to
satisfaction ratings such that a major feature of the delivery of care, the
experience of friendliness and caring from staff, was related more highly to
satisfaction with care than to satisfaction with outcome, while measures of
clinical outcome were related more highly to satisfaction with outcome than to
satisfaction with care. A general disposition to be satisfied, therefore, appears
not to have a major biasing effect on satisfaction with treatment. Further,
patients appear to make valid differentiations between satisfaction with the
delivery of care and the clinical outcome of care when their attention is focused
specifically on satisfaction with these features.
PMID- 17041292
TI - Diagnosing major depressive disorder VIII: are some symptoms better than others?
AB - The present report from the Rhode Island Methods to Improve Diagnostic Assessment
and Services project examined whether symptoms that are not part of the DSM-IV
definition of major depressive disorder (MDD) are better at discriminating
depressed from nondepressed patients than the current criteria. Symptoms assessed
included diminished drive, helplessness, hopelessness, nonreactive mood, psychic
anxiety, somatic anxiety, subjective anger, and overtly expressed anger. A total
of 1538 psychiatric outpatients were administered a semistructured diagnostic
interview. We inquired about all of the symptoms of depression for all patients.
Diminished drive exhibited stronger performance in differentiating MDD from non
MDD relative to all DSM-IV criteria except depressed mood, reduced
interest/pleasure, and impaired concentration/indecisiveness. A compound
criterion combining diminished drive with loss of energy was endorsed by nearly
all MDD patients. Helplessness and hopelessness, when combined into a single
criterion, performed more strongly than some of the DSM-IV criteria. Lack of
reactivity, anxiety, and anger symptoms failed to differentiate more strongly
than current DSM-IV criteria. The implications of these results for revising the
diagnostic criteria for major depression are discussed.
PMID- 17041293
TI - The relationship of premorbid functioning to illness course in schizophrenia and
psychotic mood disorders during two years following first hospitalization.
AB - Studies suggest that better premorbid functioning is associated with better
outcomes in chronic schizophrenia. Yet first admission studies, which are more
appropriate to examine this, are less conclusive. Also, little attention has been
given to whether these findings hold for other psychoses. We examined the
relationship of premorbid functioning using the Premorbid Adjustment Scale and
outcomes in first admission psychoses (schizophrenia, N = 177; bipolar disorder,
N = 106; major depression, N = 68) in the Suffolk County-wide mental health
project. Poor premorbid functioning was associated with worse outcomes in all
three diagnostic groups. Specifically, it was associated with more negative
symptoms early in the course of illness, less improvement in negative symptoms,
poorer overall clinical functioning, and poorer social functioning. Consistent
with new epidemiological research, early assessment of premorbid functioning
could provide an avenue for targeted interventions that might improve outcomes.
PMID- 17041294
TI - Negative bias in the perception of others' facial emotional expressions in major
depression: the role of depressive rumination.
AB - Depressed individuals display a negative bias in the perception of others' facial
emotional expressions. The extent of this selective processing, moreover, has
proven predictive of a poor outcome in depression. However, to date, little is
known about the possible mechanisms that may account for this bias. This study
examined the hypothesis that rumination--an analytical type of self-focused
attention--would be associated with higher levels of perception of negative
facial emotions in major depression. Twenty-six depressed patients (17 women)
completed the Perception of Facial Expressions Questionnaire, the Ruminative
Response Scale, and other measures assessing depression-related constructs.
Consistent with prediction, rumination was positively related to a negative bias
in the judgment of facial expressions, even when controlling for other depression
related variables. Although the correlational design of the present study limits
the extent to which conclusions can be drawn on the directionality of the
observed relationship, the present study reveals self-focused rumination as a
possibly important causal mechanism in explaining depressed persons' negative
bias in the perception of others' facial emotions.
PMID- 17041295
TI - Risk factors for long-term posttraumatic stress reactions in unarmed UN military
observers: a four-year follow-up study.
AB - Follow-up data from 187 male Norwegian veteran officers from unarmed UN military
observer missions were compared with follow-up data from 211 male veteran
officers from Norwegian contingents of the UNIFIL peacekeeping mission in South
Lebanon on stress exposure, posttraumatic stress symptoms, level of alcohol
consumption, and problems with social adaptation after redeployment from the
mission. Observer mission veterans reported exposure to significantly higher
levels of war zone stressors than veterans from peacekeeping units did. Observer
veterans also reported significantly more posttraumatic stress symptoms at follow
up, higher alcohol consumption levels during service and at follow-up, and more
problems with social adaptation to their lives at home in the years after their
UN military service. All of these difficulties were most prominent in observers
having served in missions with high-intensity stress exposure. Multivariate
analyses demonstrated stress exposure during the mission and problems with social
adaptation after homecoming to predict posttraumatic stress symptoms at follow
up.
PMID- 17041296
TI - Professional competencies for applied epidemiologists: a roadmap to a more
effective epidemiologic workforce.
PMID- 17041298
TI - A comprehensive Laboratory Services Survey of State Public Health Laboratories.
AB - In November 2004, the Association of Public Health Laboratories (APHL) conducted
a Comprehensive Laboratory Services Survey of State Public Health Laboratories
(SPHLs) in order to establish the baseline data necessary for Healthy People 2010
Objective 23-13. This objective aims to measure the increase in the proportion of
health agencies that provide or assure access to comprehensive laboratory
services to support essential public health services. This assessment addressed
only SPHLs and served as a baseline to periodically evaluate the level of
improvement in the provision of laboratory services over the decade ending 2010.
The 2004 survey used selected questions that were identified as key indicators of
provision of comprehensive laboratory services. The survey was developed in
consultation with the Centers for Disease Control and Prevention National Center
for Health Statistics, based on newly developed data sources. Forty-seven states
and one territory responded to the survey. The survey was based on the 11 core
functions of SPHLs as previously defined by APHL. The range of performance among
individual laboratories for the 11 core functions (subobjectives) reflects the
challenging issues that have confronted SPHLs in the first half of this decade.
APHL is now working on a coordinated effort with other stakeholders to create
seamless state and national systems for the provision of laboratory services in
support of public health programs. These services are necessary to help face the
threats raised by the specter of terrorism, emerging infections, and natural
disasters.
PMID- 17041297
TI - Fear of terrorism and preparedness in New York City 2 years after the attacks:
implications for disaster planning and research.
AB - OBJECTIVES: To help improve disaster planning and research, we studied
psychosocial predictors of terrorism fear and preparedness among New York City
residents after the World Trade Center disaster (WTCD). METHOD: We conducted a
random cross-sectional survey of 1,681 adults interviewed 2 years after the WTCD.
Participants were living in New York City at the time of the attack and exposed
to ongoing terrorist threats. RESULTS: We found 44.9 percent (95% confidence
interval [CI] = 41.9-47.9) of residents were concerned about future attacks and
16.9 percent (95% CI = 14.7-19.3) reported a fear level of "10" on a 10-point
analog scale. Furthermore, 14.8 percent (95% CI = 12.8-17.0) reported they had
made some plans for a future attack, a significant increase from the previous
year. In addition, although 42.6 percent (95% CI = 39.6-45.7) indicated that they
would likely wait for evacuation instructions following a chemical, biological,
or nuclear attack, 34.4 percent (95% CI = 31.5-37.3) reported they would evacuate
immediately against official advice. Predictors of high terrorism fear in a
multivariate model included Hispanic ethnicity (odds ratio [OR] = 2.0, P = .006),
lower education (OR = 4.4, P < .001, and OR = 3.7, P < .001, respectively, for
nonhigh school and high school graduates, compared with college graduates), being
exposed to stressful life events (OR = 1.6, P = .048), having current
posttraumatic stress disorder (3.1, P < .001), having a fear of death (OR = 2.5,
P = .002), and reporting a likelihood of fleeing an attack against advice (OR =
1.5, P = .034). The best predictors of preparedness in a multivariate model was
being between 30 to 64 years old (30-44 years old, OR = 2.6, P = .001; 45-64
years old, OR = 1.8, P = .03, respectively, compared with 18-29 years old),
having higher exposure to the WTCD (moderate exposure, OR = 1.7, P = .05; high
exposure, OR = 2.4, P = .002; very high exposure, OR = 4.1, P < .001),
respectively, compared with no little WTCD exposure), and having greater exposure
to other lifetime traumatic events (high traumatic event exposure, OR = 2.1, P =
.005, compared with no exposure). CONCLUSION: Our study suggests that among those
exposed to ongoing terrorism threats, terrorism fear and preparedness were
related to socioeconomic factors, mental health status, terrorism exposure
levels, and exposure to stressful life events.
PMID- 17041299
TI - Local public health agency performance and community health status.
AB - This study describes the results of an analysis of the relationship between local
public health agency performance and health outcomes. Findings support the model
that local public health agency performance affects community health status, and
depending on the outcome, performance contributions vary. New hypotheses are
offered that could help determine how system performance affects health outcomes.
PMID- 17041300
TI - The Local Public Health System Assessment of MAPP/The National Public Health
Performance Standards Local Tool: a community-based, public health practice and
academic collaborative approach to implementation.
AB - The Local Public Health System Assessment (LPHSA) in Mobilizing for Action
through Planning and Partnerships (MAPP), and the Local Tool of the National
Public Health Performance Standards Program (LT/NPHPSP)--which are one in the
same-attempt to assess the capacity to provide the essential public health
services. Both tools have been utilized in various public health practice
settings; however, users have been challenged with the complexity of the tools
and time and human resource investment necessary to complete them. The recent
Journal of Public Health Management and Practice issue focus on MAPP provided
several examples of LPHSA implementation, both as a component of MAPP and as a
stand-alone activity in the context of performance standards. The uniqueness in
our approach involved a collaborative between a community-based organization, a
public health academic program, and a governmental public health agency which
conducted the LPHSA in a manner that did not require actual modification of the
tool itself, was practical and feasible, and was of benefit and value to all
partners.
PMID- 17041301
TI - Using principles of community-based participatory research to enhance health data
skills among local public health community partners.
AB - In a prior statewide health disparities assessment, local community public health
and social service professionals indicated a need for technical capacity growth
in order to understand and effectively utilize health data. Using a community
based participatory research approach in addressing this need, health data
training was provided to 26 individuals with the primary goals being to provide
capacity to identify health disparities that result in higher morbidity and
mortality, and to provide the skills needed to access, interpret, and utilize
health data. Satisfaction surveys showed that an overwhelming majority of
participants were extremely pleased with the training. Follow-up telephone
interviews (100% response rate) conducted 2 months after the training indicated
positive results, with participants discussing how they felt empowered to find,
interpret, and use data as a result of the training. Results of a 6-month follow
up questionnaire (54% response rate) further supported the program's desired
outcome to expand participants' knowledge and use of health data. This pilot
project illustrated how utilizing a community-level partnership approach to
program development not only enhances the utilization of such programs but also
helps sustain participants' knowledge and skills.
PMID- 17041302
TI - Evaluation of the timeliness and completeness of a Web-based notifiable disease
reporting system by a local health department.
AB - OBJECTIVE: To evaluate the completeness and timeliness of the Colorado statewide
Web-based system for reporting notifiable diseases, called the Colorado
Electronic Disease Reporting System. This project demonstrates how a local health
department can conduct a surveillance evaluation to identify areas of
improvement. METHODS: Reports received by Colorado for 2004 were categorized as
Tri-County Health Department (TCHD) reports and reports received for the rest of
Colorado. Report completeness and timeliness were compared for all diseases
routinely followed up by TCHD for both datasets. A data field was considered
complete if there was data entry for that field. Timeliness in this study was
defined as the interval between "specimen collection date" and "report date" for
each record. RESULTS: Six of 12 selected data fields were 95% or more complete
for both datasets. Twenty-four-hour notifiable diseases were reported a median of
2.0 days for reports in the TCHD dataset and a median of 3.0 days for reports in
the dataset for the rest of Colorado. Seven-day notifiable diseases were reported
a median of 4.0 days for both datasets. CONCLUSIONS: Both Colorado datasets were
found to be relatively complete and timely. Improved data collection by
interviewers will help better determine demographic information of reported cases
and timeliness of reports.
PMID- 17041303
TI - Applying comprehensive community-based approaches in diabetes prevention:
rationale, principles, and models.
AB - The literature regarding the prevention of diabetes provides few standards for
community-based initiatives. The present article offers four principles for
engaging communities in comprehensive community approaches to diabetes prevention
including (1) facilitating meaningful and central roles for communities, (2)
giving primary attention to participatory processes rather than to best
practices, (3) emphasizing cultural relevance in designing interventions
particularly in racial and ethnic communities, and (4) incorporating social
ecology approaches that are holistic and that address larger environmental
influences rather than individual behavioral change alone. In order that
community public health practitioners may operationalize the principles, models
are provided for each.
PMID- 17041304
TI - Low-fat milk and high-fiber bread availability in food stores in urban and rural
communities.
AB - As part of the Albany Prevention Research Center's Core Project to understand
environmental influences on a healthy lifestyle, all food stores in downtown
Albany (N=79) and rural Columbia and Greene counties (N=177) in New York State
were visited and surveyed for their availability of low-fat milk and high-fiber
bread. Stores in the rural community were significantly (P < .01) more likely to
stock low-fat milk (71%) and high-fiber bread (55%) than stores in Albany (40%
and 33%, respectively). The rural community also had a significantly higher
population ratio of "healthy milk & bread (M&B) stores" (carrying both items)
than Albany (7.6 vs 3.9 per 10,000 residents). Urban healthy M&B stores were more
likely to be a convenience store and accept food stamps, whereas rural healthy
M&B stores were more likely to be a gas station store and offer off-street
parking. Multiple logistic regression analysis found that healthy M&B stores were
inversely associated with proportions of ethnic/racial minorities in the census
block group (CBG). More than 80 percent of minorities in Albany resided in a CBG
without a healthy M&B store. Urban residents in predominantly minority
neighborhoods were most likely to encounter environmental barriers to obtain
healthy staple food, and intervention should be tailored to aid this population.
PMID- 17041305
TI - Identifying housing that poisons: a critical step in eliminating childhood lead
poisoning.
AB - The purpose of our study was to develop a method to identify and prioritize "high
risk" buildings in Chicago that could be targeted for childhood lead poisoning
prevention activities. We defined "high-risk" buildings as those where multiple
children younger than 6 years with elevated blood lead levels (BLLs) had lived
and where lead hazards were previously identified on environmental inspection. By
linking 1997-2003 Chicago elevated blood lead surveillance, environmental
inspection, and building footprint data, we found that 49,362 children younger
than 6 years with elevated BLLs lived at 30,742 buildings. Of those, 67 were
"high-risk" buildings and these were associated with 994 children with elevated
BLLs. On average, 15 children with elevated BLLs had lived in each building
(range: 10-53, median: 13). Almost two thirds (n = 43) of the high-risk buildings
had two or more referrals for inspection to the same apartment or housing unit;
of those, 40 percent (n = 17) failed to maintain lead-safe status after
compliance. Linking blood lead surveillance, environmental inspection, and
building footprint databases allowed us to identify individual high-risk
buildings. This approach prioritizes lead hazard control efforts and may help
health, housing, and environmental agencies in targeting limited resources to
increase lead-safe housing for children.
PMID- 17041306
TI - Validity of self-reported health plan information in a population-based health
survey.
AB - OBJECTIVE: To validate information on private health insurance coverage in a
population-based study. METHODS: Respondents to the Massachusetts Behavioral Risk
Factor Surveillance System were asked the name of their health plan company
(affiliation) and specific brand of insurance (product), the duration in which
they belonged to the plan, and demographic and health-related data. Information
on plan affiliation and product was used to classify individuals on type of
coverage. At the end of the survey, respondents with health insurance were asked
to retrieve their health plan cards, and to read detailed information from the
cards. Self-reported data were compared with information from the cards. RESULTS:
Self-reported information on health plan affiliation agreed with plan cards for
93 percent of individuals, while agreement was 79 percent for health plan
product. Among health maintenance organization (HMO) participants, 93 percent
correctly reported being in an HMO (sensitivity), whereas 76 percent of
respondents in a non-HMO plan correctly self-reported (specificity). Individuals
with higher levels of income, those with a primary care doctor, and those in a
health plan for at least 1 year had higher agreement. Higher validity was
associated with poor physical health and recent cancer screening. CONCLUSIONS:
Self-reported data on health plan affiliation and product have good validity in a
population-based sample of adults. While agreement differs according to specific
respondent characteristics, these differences do not appear substantial.
PMID- 17041308
TI - The continued spread of HIV in the United States: prevention failure or systems
defect?
PMID- 17041307
TI - A comparison of breastfeeding rates in an urban birth cohort among women
delivering infants at hospitals that employ and do not employ lactation
consultants.
AB - OBJECTIVE: To compare rates of breastfeeding at hospital discharge between
facilities that employ and do not employ International Board Certified Lactation
Consultants (IBCLCs). METHODS: This study used a cross-sectional design. Data
from 11,525 birth certificates of Philadelphia residents who delivered in 2003
were used. Breastfeeding was assessed using a question included on the
Pennsylvania birth record, "Is the infant being breastfed at discharge?" The
Philadelphia Department of Public Health's lactation consultants collected
information on number of hours worked annually by IBCLCs by facility. RESULTS:
After adjusting for race/ethnicity, education, insurance status, age, marital
status, route of delivery, birth weight, and gestational age, delivering in a
hospital that employed an IBCLC was associated with a 2.28 (95% confidence
interval [CI] =1.98,2.62) times increase in the odds of breastfeeding at hospital
discharge. Among women receiving Medicaid, delivering at a hospital that employed
IBCLCs was associated with a 4.13 (95% CI =3.22,4.80) times increase in the odds
of breastfeeding at hospital discharge. CONCLUSIONS: The findings presented here
identify an association between delivering at a facility that employs IBCLCs and
breastfeeding at hospital discharge. As the strength of this association is not
negligible, particularly for women on Medicaid, these findings may be used to
encourage widespread use of IBCLCs.
PMID- 17041309
TI - The behavioral event interview: avoiding interviewing pitfalls when hiring.
AB - The Management Moment" is a regular column within the Journal of Public Health
Management and Practice. Edward L. Baker, MD, MPH, MSc, is serving as The
Management Moment Editor. Dr Baker is Director of The North Carolina Institute
for Public Health, School of Public Health, at the University of North Carolina
at Chapel Hill. This column provides commentary and guidance on timely management
issues commonly encountered in public health practice.
PMID- 17041310
TI - Searching for lessons from the New Orleans Health Department: implications for
public health practice.
AB - The National Association footline of County and City Health Officials (NACCHO) is
the national organization representing local health departments. NACCHO supports
efforts that protect and improve the health of all people and all communities by
promoting national policy, developing resources and programs, seeking health
equity, and supporting effective local public health practice and systems.
PMID- 17041312
TI - The global sex disparity in blindness and visual impairment.
PMID- 17041315
TI - Central corneal epitheliopathy in a long-term, overnight orthokeratology lens
wearer: a case report.
AB - PURPOSE: The purpose of this study is to report an unusual case of central
corneal epitheliopathy (CCE) in a long-term orthokeratology lens wearer. CASE
REPORT: A single observational case report of a 12-year-old Chinese female myope
with 3(1/2) years' experience in wearing orthokeratology lenses overnight was
diagnosed with a CCE lesion during her regular orthokeratology aftercare
consultation. The patient was asymptomatic. Trace or almost negative fluorescein
staining was observed over the particular lesion area and, according to the
clinical features of the corneal lesion, was thought to be a partially formed
"dellen." The lesion healed after the use of the orthokeratology lenses was
suspended for 4 months and reappeared when the patient resumed wearing the
lenses. Close monitoring of the corneal condition was needed on this patient, and
permanent discontinuation of the orthokeratology procedures will be considered if
the signs and symptoms of the lesion worsen. DISCUSSION: The etiology, clinical
management and the possible differential diagnosis of the central cornea "dellen"
are discussed. CONCLUSION: A central corneal "dellen" may be associated with long
term, overnight use of orthokeratology lenses.
PMID- 17041316
TI - The morphology of the palpebral fissure in different directions of vertical gaze.
AB - PURPOSE: The purpose of this study is to investigate the normative morphology of
the palpebral fissure by measuring a range of biometric eye dimensions for a
population of young subjects through analysis of digital images in primary gaze
and two typical angles of downward vertical gaze. Palpebral fissure
characteristics are clinically important in areas such as contact lens practice.
METHODS: High-resolution digital images were taken of 76 young subjects with a
range of refractive errors in primary gaze and 20 degrees and 40 degrees downward
gaze. The digital images were analyzed to ascertain a range of biometric measures
of the palpebral fissure for each subject in each angle of gaze. Repeated
measures analysis of variance was used to investigate changes occurring in the
palpebral fissure dimensions with vertical angle of gaze. RESULTS: Highly
significant changes were found to occur in the horizontal and vertical palpebral
fissure dimensions, the palpebral fissure angle, and the eyelid contour as a
function of angle of gaze. The palpebral fissure narrows in the vertical
dimension (from an average vertical palpebral aperture width for white subjects
in primary gaze of 9.7+/-1.2 mm to an average width of 6.4+/-1.1 mm in 40 degrees
downgaze), shortens in the horizontal dimension (from average horizontal
palpebral aperture width of 27.1+/-1.5 mm in primary gaze to an average of 25.6+/
1.8 mm in 40 degrees downgaze), and becomes more "down-slanted" with increasing
downward gaze. CONCLUSIONS: Highly significant changes to the palpebral fissure
dimensions occur in downward vertical gaze. These changes are important because
many visual tasks are performed in downward gaze. These findings have
implications for the management of lid anomalies and for contact lens fitting and
design.
PMID- 17041317
TI - Temporal progression and spatial repeatability of tear breakup.
AB - PURPOSE: This study used image analysis to compare the temporal progression and
spatial reoccurrence of the area of tear film breakup (AB) in dry eye and normal
subjects. METHODS: Tear breakup was induced in 10 control and 10 dry eye subjects
during the Staring Tear Breakup Dynamics (S-TBUD) test, which involves keeping
one eye open for as long as possible, termed the maximum blink interval (MBI).
Video imaging of tear film fluorescence measured the onset and progression of the
AB. AB location and area were mapped. The progression of ABs from the first
trial, the rate of tear breakup or dry area growth rate (DAGR), and the overlap
of ABs in three successive trials 5 minutes apart were computed by custom MATLAB
programs. RESULTS: The final AB before the blink was significantly greater
(average, 30.7%+/-12.5% vs. 16.1%+/-9.2%) and the MBI was significantly less
(average, 19.5+/-9.0 seconds vs. 56.5+/-38.9 seconds) among dry eye subjects
compared with controls (p<0.05, Mann-Whitney U test). The DAGR was four times
greater among dry eye subjects, who also showed significantly more tear breakup
in the central cornea than controls (p<0.0001, Mann-Whitney U test). When the
final image from three successive trials was overlapped, tear breakup occurred
more often in the same location in three trials than would be expected by the
overlap of independent points. CONCLUSIONS: Structural influences such as the
"black line" or corneal lid defects appeared to influence the recurrence of
breakup in the same region. The S-TBUD quantitative image analysis technique
demonstrates that the tear film of subjects with dry eye continues to rapidly
destabilize after an initial first break; thus, a low TBUT was combined with a
high DAGR. The central corneal region of subjects with dry eye appeared
especially susceptible to increased tear breakup when compared with controls.
PMID- 17041318
TI - Tear meniscus height, lower punctum lacrimale, and the tear lipid layer in normal
aging.
AB - PURPOSE: The purposes of this study are to investigate the tear meniscus height
(TMH), lipid layer, and critical dimensions of the lower punctum lacrimale (DPL)
in normal human subjects over a large age range; and to determine the shape and
general characteristics of the lower punctum lacrimale in a normal population.
METHODS: TMH and DPL were measured using a graticule set at the eyepiece of a
slit lamp biomicroscope (magnification 32x). Lipid layer was assessed by
interferometry (Tearscope, Keeler). Only one eye (right) of each subject was
assessed. All subjects were normals without any tear-related disorders and/or
symptoms. RESULTS: Four hundred forty-four subjects were assessed (268 females,
age range, 6-91 years; 176 males, age range, 6-91 years). Mean (+/-standard
deviation) TMH in females was 0.19 mm (+/-0.11) and in males was 0.19 mm (+/
0.10). TMH was related to age (x): in females, TMH=0.13+0.0009x (r=0.2393,
p<0.001); in males, TMH=0.14+0.0008x (r=0.2492, p<0.001). TMH increased from 0.15
mm (+/-0.06) in the young (<20 years) to 0.21 mm (+/-0.10) in the elderly (>80
years). The punctum was closed in 10.8%, slit shaped in 24.3%, oval in 5.4%, and
round in 59.5% of all cases. Mean age and TMH of those presenting with closed
puncta was significantly higher than those presenting with open puncta (p<0.001).
Mean (+/-standard deviation) area of open puncta was 0.008 mm (+/-0.013) in
females and 0.010 mm (+/-0.018) in males. The difference was not significant.
Diameter of round puncta was inversely related to age in females (r=-0.4985,
n=149, p<0.001) but not within the males. A total of 14.6% of females and 12.5%
of males presented with no discernible lipid layer. Lipid layer tended to be
thinner in older subjects (one-way analysis of variance, F=6.667, p<0.001). There
was no clear relationship between TMH and the lipid layer. CONCLUSIONS: There is
a gradual increase in TMH and shift in size and shape of the punctum lacrimale
with advancing years. Age-related changes in the lipid layer are expected to
reduce tear volume by way of increased evaporation. On balance, it would appear
any effects on tear volume by a thinning lipid layer are outweighed by changes in
the puncta.
PMID- 17041319
TI - Rigid gas-permeable contact lens base curve radius and transmissibility effects
on corneal oxygen uptake.
AB - PURPOSE: The purpose of this study is to determine the effects of rigid gas
permeable contact lens thickness, base curve radius, and material permeability on
corneal hypoxic stress. METHODS: Corneal oxygen uptake rates were measured with a
Clark-type polarographic electrode on the right eye of 10 human subjects for the
normal open eye (air) and after 5 minutes of static wear of rigid contact lenses
of four cornea-to-contact lens base curve fitting relationships: 0.2 mm steeper
than-K (STK), 0.1 mm STK, on K, and 0.1 mm flatter-than-K (FTK). There were also
four materials (polymethylmethacrylate [Dk=0], lotifocon B [OP-2, Dk=15.9],
lotifocon A [OP-3, Dk=30], lotifocon C [OP-6; Dk=60]) and three center
thicknesses (0.14, 0.28, and 0.53 mm for the OP-6 lenses and 0.14 mm for all
other materials) with all other parameters being constant. Each subject
participated in two identical sessions. A repeated-measures analysis of variance
was performed to compare the mean response across lens materials/thicknesses and
the four curvature values. RESULTS: Significant differences were found only for
lens material/thickness (p<0.0001). Although OP-2 and OP-6 (0.53 mm) were
manufactured to have the same Dk/t, post hoc comparisons showed that the oxygen
uptake rate with OP-6 (0.53 mm) was significantly lower. The same is also true
for OP-3 and OP-6 (0.28 mm), with OP-6 (0.28 mm) having a significantly lower
oxygen uptake rate. CONCLUSIONS: In contrast to past studies with PMMA, cornea-to
contact lens base curve fitting relationship, with the lens materials and designs
studied here, did not affect corneal hypoxic stress, and thick, high Dk lenses
resulted in less change in corneal response than did thin, lower Dk lenses of the
same Dk/t. This is attributed to the lens reservoir effect that has been
previously described.
PMID- 17041320
TI - Reduced corneal swelling and deswelling response in the iridocorneal endothelial
syndrome.
AB - PURPOSE: Despite severe abnormalities of the corneal endothelium in the
iridocorneal endothelial (ICE) syndrome, the cornea can remain clear and maintain
its normal thickness for years before corneal decompensation occurs. The aim of
this study is to analyze this discrepancy by studying corneal hydration control
in the ICE syndrome. METHODS: In four subjects with unilateral ICE syndrome,
without signs of corneal decompensation, a "corneal stress test" was performed in
both the affected and the unaffected eye. The stress test measures the recovery
of corneal thickness after swelling induced by wearing a soft contact lens with
the eyes closed. Corneal thickness was measured by noncontact pachymetry.
RESULTS: Mean baseline corneal thickness of affected eyes (535+/-56 microm) was
not different from unaffected eyes (526+/-39 microm). On the other hand, the
corneal stress test showed a smaller induced swelling in affected eyes (33+/-15
microm) compared with unaffected eyes (67+/-11 microm) and a slower recovery of
corneal thickness in affected eyes. In one of four subjects, the cornea of the
affected eye was calculated not yet to have recovered its original thickness
before midnight. After this finding, although the cornea of this subject did not
show any signs of clinical decompensation, the study was discontinued.
CONCLUSIONS: Corneal hydration control is altered in the ICE syndrome. The ICE
cornea can maintain its normal thickness despite severe morphologic abnormalities
of the endothelium. Because we found that recovery of corneal thickness can be
extremely slow, it cannot be guaranteed that such corneal "stress tests" are
completely safe for subjects with the ICE syndrome, and we therefore feel that
they should no longer be performed in these subjects.
PMID- 17041321
TI - Deposition rates and lens care influence on galyfilcon A silicone hydrogel
lenses.
AB - PURPOSE: The purpose of this study is to investigate the frequency of deposition
and impact of various multipurpose care regimens on a silicone hydrogel contact
lens material (galyfilcon A; Acuvue Advance, Vistakon, Inc.). METHODS: This was a
two-phase, monadic, open-label, daily-wear clinical study. The analyses from
Phase I were aimed at determining total lens front surface area deposition after
two 2-week periods of galyfilcon A lens wear. Deposition was graded clinically
using a slit-lamp biomicroscope from grade 0 (0% surface area) to grade 4 (>25%
surface area). Secondary outcomes included visual acuity and self-reported
overall comfort, end-of-day comfort, and perceived vision. Phase II determined
the impact of various multipurpose solutions with and without a rub step on
"heavy depositors" (grade 3 or 4) from a single phase I site. There were four
arms associated with phase II, and front surface deposition was again the primary
outcome with the same secondary outcomes as that mentioned previously. RESULTS:
In phase I, after the initial 2-week wear period, 9.4% of subjects exhibited
grades 3 and 4 deposition. There were no differences in visual acuity, comfort,
end-of-day comfort, and self-reported perceived vision when comparing
"depositors" and "nondepositors." Twenty-seven "heavy depositors" from phase I
completed phase II. After using Complete MoisturePlus (with a digital rub), no
patients (0%) had clinically significant (grades 3 or 4) deposition, whereas for
comparison, 33% of patients (the "heavy depositors") from phase I had clinically
significant deposition without a digital rub (p=0.003). Similarly, 3.7% of
patients had grade 3 or 4 deposition after using Opti-Free Express (with a
digital rub) (p=0.01) and AOSEPT with a Miraflow-based rub (p=0.01) compared with
the 33% of patients using Complete MoisturePlus without a digital rub. There were
no differences in visual acuity or self-reported outcomes when stratified by lens
care system in phase II. CONCLUSIONS: Less than 10% of subjects exhibit
clinically significant levels of deposition with galyfilcon A lenses when cleaned
with Complete MoisturePlus (no-rub) multipurpose solution, and this was shown to
not interfere with lens performance. The addition of a rub-and-rinse step to the
care of galyfilcon lenses significantly reduces this deposition rate.
PMID- 17041322
TI - Objective and subjective responses in patients refitted to daily-wear silicone
hydrogel contact lenses.
AB - PURPOSE: Silicone hydrogel (SiH) lenses offer many physiological advantages for
daily wear (DW) in addition to the continuous-wear modality for which they were
originally developed. The purpose of this study was to investigate the clinical
performance and physiological responses in a group of successful long-term
wearers of conventional hydrogel lenses when refitted with DW SiH contact lenses.
METHODS: Eighty-seven successful soft lens wearers (8.4+/-4.7 years of prior lens
wear) participated in this study. Bulbar and limbal hyperemia were subjectively
graded and digitally photographed for subsequent masked objective evaluation.
Subjective symptoms were scored using visual analog scales. In addition,
refractive error, corneal curvature, and corneal thickness were measured. All
subjects were refitted with Focus Night & Day (lotrafilcon A) SiH lenses;
however, to reduce the potential for bias, they were informed that they were
being randomly assigned to wear either low oxygen permeability (Dk) lenses or
high Dk SiH lenses and were "masked" as to their lens assignment. Subjects
returned after 1 week, 1 month, and 2 months of DW, at which time all gradings,
photographs, and measurements were repeated. End-of-day subjective symptoms were
also graded periodically during the study. RESULTS: Ninety-three percent of
subjects were successfully refitted. Both objective and subjective evaluations
showed that bulbar and limbal hyperemia decreased significantly in all quadrants
during the study (p<0.001), particularly for those subjects with greater baseline
hyperemia (p<0.001). Subjects reported a concurrent reduction in end-of-day
dryness and improved end-of-day comfort compared with their habitual lenses
(p<0.001). No significant changes in refractive error, tarsal papillary response,
corneal curvature, or corneal thickness were found during the study. CONCLUSIONS:
Hyperemia in contact lens wearers may be attributed to a number of factors,
including hypoxia. Refitting existing low Dk lens wearers with SiH lenses on a DW
basis can result in a decrease in hyperemia, which may be significant for some
subjects and also results in improvements in symptoms of dryness and discomfort.
PMID- 17041323
TI - A comparison of wavefront aberrations in eyes wearing different types of soft
contact lenses.
AB - PURPOSE: The purpose of this study is to investigate the optical quality of eyes
wearing different types of soft contact lenses (sCLs) using wavefront
aberrometry. METHOD: A psychophysical aberrometer (WFA1000B; BriteEye, SuZhou,
China) was used to measure wavefront aberrations for 56 eyes of 28 subjects under
four conditions: 1) without contact lenses (non-CL), 2) with lathe-cut contact
lenses (lathe-cut CL; Shuliang, Weicon Optics, Shanghai, China), 3) with cast
molded contact lenses (cast-molded CL; Vistavue, J&J Vision Care, U.S.), and 4)
with spun-cast contact lenses (spun-cast CL; Lanfenzhiji, Justcome Optics,
Beijing, China). The three types of sCLs were made from different materials and
lens design. The root mean square (RMS) values of the wavefront aberrations and
individual Zernike aberrations were calculated and compared among the CL-wearing
conditions. RESULTS: Astigmatism was not significantly changed by any of the
three soft contact lenses when compared with the non-CL condition. However, a
significant difference in the RMS values of higher-order aberrations was observed
between the lens types (F=8.29, p<0.0001). Induced higher-order aberrations were
found for both the cast-molded CL and the spun-cast CL conditions. There were
significant differences in the aberrations in each of the higher orders between
the CL conditions (F=3.77, p=0.011 for third order; F=5.31, p=0.002 for fourth
order; F=13.86, p<0.0001 for fifth and higher orders). More higher-order Zernike
aberrations such as coma and spherical aberration were induced by cast-molded CLs
and/or the spun-cast CLs. CONCLUSION: Wavefront aberrations in the eyes with soft
contact lenses vary from one individual lens type to another. Although the
variation in wavefront aberrations could be attributed to the differences in the
methods of manufacture, influences from other factors such as the lens material
and lens design could not be excluded and deserve further investigation.
PMID- 17041324
TI - History of mirrors dating back 8000 years.
AB - PURPOSE: The purpose of this study is to consider the ancient history and early
development of mirrors, because mirrors played a key role in refraction and
magnification for an extended period of time before the invention of spectacles,
including broad use in Roman times. FINDINGS: The earliest known manufactured
mirrors (approximately 8000 years old) have been found in Anatolia (south central
modern-day Turkey). These were made from obsidian (volcanic glass), had a convex
surface and remarkably good optical quality. Mirrors from more recent periods
have been found both in Egypt and Mesopotamia and still later in China and in the
New World. In each of these areas, mirrors were in use by approximately 2000 BC
or 4000 years ago.
PMID- 17041325
TI - Another look at synovial fluid leukocytosis and infection.
AB - Synovial fluid white blood cell counts are considered to be useful in diagnosing
infectious arthritis, however, considerable overlap exists between infectious and
noninfectious types of inflammatory arthritis. We undertook this review of
synovial fluid studies at our institution to better define this degree of overlap
and characterize the features of infectious arthritis in relationship to synovial
fluid white cell counts. The records of 202 consecutive patients with synovial
fluid white blood cell counts >2000/mm were reviewed. Infectious arthritis was
diagnosed in 77% (10/13) of patients with counts >100,000, 47% (8/17) in the
50,000-100,000 range, and 5% (9/172) with counts <50,000. Crystal-induced
arthritis and rheumatoid arthritis made up 81% of patients in the 15,000-50,000
range. Overall, 10 of 27 (37%) cases of infectious arthritis had white cell
counts >100,000, and 18 of 27 (67%) had counts >50,000. A majority of these
infections (14/18) were related to Staphylococcus aureus, while 5 of 7 infections
associated with counts <20,000 were associated with atypical organisms. This
study confirms that a majority of patients with very high synovial fluid white
blood cell counts have infectious arthritis, and that the likelihood of infection
is markedly reduced, but certainly not excluded, below this level. The presence
of atypical infections in a small percentage of patients with low counts
emphasizes the importance of clinical judgment in evaluating all patients with
inflammatory arthritis, regardless of synovial fluid white cell counts.
PMID- 17041326
TI - Fibromyalgia pain and substance P decrease and sleep improves after massage
therapy.
AB - Massage therapy has been observed to be helpful in some patients with
fibromyalgia. This study was designed to examine the effects of massage therapy
versus relaxation therapy on sleep, substance P, and pain in fibromyalgia
patients. Twenty-four adult fibromyalgia patients were assigned randomly to a
massage therapy or relaxation therapy group. They received 30-minute treatments
twice weekly for 5 weeks. Both groups showed a decrease in anxiety and depressed
mood immediately after the first and last therapy sessions. However, across the
course of the study, only the massage therapy group reported an increase in the
number of sleep hours and a decrease in their sleep movements. In addition,
substance P levels decreased, and the patients' physicians assigned lower disease
and pain ratings and rated fewer tender points in the massage therapy group.
PMID- 17041327
TI - Cognitive and dissociative manifestations in fibromyalgia.
AB - Memory decline and mental confusion frequently complicate the clinical
presentation of fibromyalgia; however, formal cognitive examination often does
not support deterioration. This paradox was examined in the context of
dissociation, a condition with many cognitive similarities. Dissociation refers
to the separation of parts of experience from the mainstream of consciousness. A
common example is highway hypnosis. Eighty-nine fibromyalgia (FM) patients and 64
other rheumatic disease patients were screened for memory decline and mental
confusion using a questionnaire format. Pain, dissociation, affective distress,
fatigue, sleep difficulty, and mental confusion were also assessed. Cognitive
complaints (76.4%-43.8%) and dissociative symptoms (37.1%-1.9%) were
overrepresented in patients with FM. Among FM patients with high dissociation,
cognitive difficulties were reported by 95%; 100% of these cases reported that
both memory and mental clarity were affected, a condition referred to as
fibrofog. Dissociation in combination with fibrofog was associated with higher
levels of FM symptom intensity and decreased mental well being. These findings
suggest that dissociation may play a role in FM symptom amplification and may aid
in comprehending the regularity of cognitive symptoms. Separating cases of
fibrofog from cognitive conditions with actual brain damage is important. It may
be prudent to add a test of dissociation as an adjunct to the evaluation of FM
patients in cases of suspected fibrofog. Otherwise, test results may prove normal
even in patients with disabling cognitive symptoms.
PMID- 17041328
TI - Neutrophilic myositis: an extra-intestinal manifestation of ulcerative colitis.
AB - Myositis of the skeletal muscle is rarely seen as an extraintestinal
manifestation of inflammatory bowel disease. We report a case of a 36-year-old
man with ulcerative colitis who developed 3 episodes of steroid responsive
myositis in a 4-month period. He presented with a blistering rash followed by
pain and massive swelling in the right shoulder and lower extremities, with
marked elevation in muscle enzymes. Diagnosis of myositis was made after a muscle
biopsy, which showed neutrophilic infiltrate in the deep subcutaneous tissue and
skeletal muscle. Review of the literature indicates only a few cases of myositis
associated with ulcerative colitis, most of them during an acute exacerbation of
the disease. However, the present patient had his first episode when the
ulcerative colitis was in remission. Myositis in ulcerative colitis may present
atypically, in particular mimicking pyomyositis. Clinicians should be aware of
this unusual steroid-sensitive complication.
PMID- 17041329
TI - Pseudoxanthoma elasticum masquerading as Sjogren's syndrome.
AB - Pseudoxanthoma elasticum is an inherited disorder of abnormal calcification of
elastic fibers in the skin, retina, and cardiovascular system. Herein, we report
a patient who had dry eyes and mouth, keratoconjunctivitis sicca, and a low titer
ANA at presentation. A lip biopsy was performed to confirm a clinical suspicion
of Sjogren's syndrome; however, the histologic findings were diagnostic of
pseudoxanthoma elasticum. Antibodies to Ro and La were negative. Subsequently,
she was found to have skin and eye findings consistent with pseudoxanthoma
elasticum. Although a causal relationship between keratoconjunctivitis sicca and
pseudoxanthoma elasticum is not proven, salivary gland involvement with
pseudoxanthoma elasticum may explain this patient's symptoms. Physicians should
consider the diagnosis of pseudoxanthoma elasticum in patients who present with
sicca symptoms without obvious cause, especially if cutaneous or ophthalmologic
abnormalities, or both, are present. Careful monitoring for associated problems
is needed as soon as pseudoxanthoma elasticum is diagnosed.
PMID- 17041330
TI - Isolated superior mesenteric artery vasculitis with response to glucocorticoids.
AB - This report describes a patient with abdominal pain at presentation, which on
angiography was found to be caused by vasculitis limited to the superior
mesenteric artery. He was treated with oral glucocorticoids after an initial 5
day course of pulse therapy and obtained excellent relief of symptoms. Steroids
were tapered over 8 months. Repeat angiography revealed complete resolution of
the vasculitis with a residual aneurysm of a branch of the left gastric artery,
which was resected to avoid the risk of rupture. Histologic analysis revealed
thickened intima with myxoid degeneration and no evidence of active vasculitis.
Extensive laboratory and clinical investigations did not reveal an underlying
connective tissue disorder to account for the gastrointestinal vasculitis. This
report of an angiographically defined regional vasculitis involving the superior
mesenteric artery with complete clinical as well as radiologic resolution on
treatment with glucocorticoids alone emphasizes the need to differentiate between
an isolated or regional vasculitis, which has an excellent prognosis, to avoid
subjecting the patient to cytotoxic therapy with significant toxicities.
PMID- 17041331
TI - Faces of eosinophilic fasciitis in childhood.
AB - Eosinophilic fasciitis is a rare connective tissue disease in children
characterized by hardening and thickening of the skin and soft tissues,
peripheral eosinophilia, elevated erythrocyte sedimentation rate, and
hypergammaglobulinemia. In this study, we report three pediatric patients with
eosinophilic fasciitis whose clinical presentation and response to therapy
differed from those reported in the literature. All three patients were female.
Two of them had Raynaud's phenomenon as an initial feature, and the third had
hepatosplenomegaly. Muscle involvement with weakness was present in two patients,
as documented not only by increased aldolase levels at the time of presentation
but also by inflammatory changes in the muscle biopsy. Serum immunoglobulin G
levels were increased only in the most severely involved patient. Peripheral
eosinophilia was present in all three cases. All three patients responded well to
prednisone therapy. Two patients had a uni-phasic course, and one required
further therapy to control a postinfection relapse. In summary, we found that
Raynaud's phenomenon and hepatosplenomegaly can be part of the spectrum of
clinical manifestations of childhood eosinophilic fasciitis. Identification as
eosinophilic fasciitis and not scleroderma, despite hand involvement and
Raynaud's phenomenon, can suggest that the illness may be steroid responsive.
PMID- 17041332
TI - Color Doppler ultrasonographic findings show tendon sheath inflammation in
mechanic's hands.
AB - Two male patients with mechanics hands and concomitant interstitial lung disease,
Raynaud's phenomenon, dermatomyositis-like rash, and arthritis were evaluated
with gray-scale ultrasonography (US) and color Doppler US of the hands using a
high-resolution hockey stick configuration 10-MHz transducer (ATL3000). Color
Doppler US and gray scale US images of the flexor tendons were obtained at the
level of the metacarpophalangeal joint. Initial gray-scale US demonstrated
subcutaneous tissue and tendon thickening and synovial sheath effusion; color
Doppler US demonstrated hyperemia of the subcutaneous tissues and tendons. Flexor
tendon dysfunction on physical examination was proportional to hyperemia and
thickening of structures shown by US. Follow-up examination, at a time when
patients were improved, showed decreased blood flow in tendon sheaths and
subcutaneous tissues and resolution of synovial sheath effusion; one patient,
however, demonstrated accumulation within the sheath. Relative improvement in
functional status mirrored the changes in the US. The color Doppler US finding of
increased blood flow in the soft tissues of these two patients with mechanic's
hands represents a physiologic anatomic abnormality amenable to treatment and
provides prognostic information for these patients. Mechanic's hands and
tenosynovitis occur in patients like these without muscle weakness.
PMID- 17041333
TI - Spinal cord compression in atypical Wegener's granulomatosis.
PMID- 17041335
TI - A surprise on joint fluid aspiration.
PMID- 17041334
TI - Molecular biology and immunology for clinicians 17: T-cell signal transduction.
AB - Peptide antigen recognition by T-cells occurs because of the interaction of the
epitope cradled within the peptide-binding groove of the major histocompatibility
complex molecule on the surface of an antigen-presenting cell with the T-cell
antigen receptor, a heterodimer whose chains belong to the immunoglobulin
superfamily. Passage of the message from the receptor to the cell's nucleus
occurs via a complex choreography of kinases, calcium, and chemical combinations
consisting of families of proteins described by arcane acronyms, numbers and
letters that perplex the casual observer. However, taming the T-cell is crucial
in transplantation and in controlling autoimmunity. Behind the jargon is a
fascinating, albeit confusing, set of mechanisms that already offer therapeutic
promise.
PMID- 17041337
TI - Chronic arthropathy in childhood and sarcoid of skin and lungs in middle age. How
are they related?
PMID- 17041338
TI - Concurrence of relapsing polychondritis and psoriatic arthritis.
PMID- 17041339
TI - Arthroscopic debridement and visco-supplementation: a minimally invasive
treatment for symptomatic osteoarthritis involving the base of the thumb.
AB - Symptomatic osteoarthritis of the base of the thumb is a common malady and is
responsible for significant morbidity. This report describes a minimally invasive
technique combining arthroscopic debridement and intraarticular visco
supplementation in patients who do not respond to more conservative measures.
Eleven patients with symptomatic osteoarthritis of the carpometacarpal joint not
responding to antiinflammatory medications, injections, and splinting underwent
arthroscopic debridement and intraarticular visco-supplementation. Using pain
relief as a measure of success, 5 patients had excellent results, 4 patients had
good results, and 2 patients had poor results. There were no complications. This
procedure may provide a bridge between more conservative palliative therapies and
the much more invasive open hand procedures currently being performed for this
problem.
PMID- 17041340
TI - Assessment of renal function in rheumatoid arthritis: validity of a new
prediction method.
AB - Medical treatment of patients with rheumatoid arthritis (RA) requires assessment
of renal function. Because determination of endogenous creatinine clearance from
a 24-hour urine collection is an unreliable and time-consuming procedure, several
formulae that predict creatinine clearance from clinical and serum parameters
have been developed. However, because of muscular atrophy, these formulae show
lower correlations with measured creatinine clearance in patients with RA than in
the healthy population. Recently, a new formula has been derived from the large
Modification of Diet in Renal Disease (MDRD) study and has been shown reliably to
predict renal function in individuals with renal dysfunction. To investigate the
validity of this method in the RA population, estimates of creatinine clearance
were derived using the most commonly used Cockcroft-Gault formula and the new
MDRD method in control subjects and patients with RA. Age, height, serum albumin,
blood urea nitrogen, and creatinine clearance were similar in both groups, but
patients with RA had a lower body weight as well as serum and urinary creatinine
concentrations. In control subjects, both methods showed comparable correlations
with measured creatinine clearance (r = 0.82 and 0.83, respectively). In patients
with RA, the Cockcroft-Gault formula revealed a lower correlation (r = 0.69) with
a moderate bias (mean error = -10.7) and prediction accuracy (mean squared error
= 342). For the MDRD method, r was still lower at 0.41, the mean error was -18.9,
and the mean squared error was 479. We conclude that in patients with RA, the
Cockroft-Gault formula is preferable to predict creatinine clearance before use
of drugs such as methotrexate or nonsteroidal anti-inflammatory drugs.
PMID- 17041342
TI - Definitely hip, but not trendy.
AB - The etiology of hip discomfort and tendinitis often is confusing and the
differential diagnosis is large. Some entities are overlooked because diagnosis
requires appropriate clinical awareness and a specific radiographic examination.
Coxa saltans, or snapping hip, is one of those commonly overlooked diagnoses.
There are three types of snapping hip--the internal type, the external type, and
the intra-articular type--and each presentation is unique. Most are symptomatic,
but some may be quite painful and disabling. Evaluating the hip structures with
bursography under dynamic conditions often is helpful to evaluate the anatomy and
determine the etiology of the snapping hip. Treatment may range from conservative
physical therapy, to corticosteroid injections, to arthroscopic treatment.
PMID- 17041343
TI - Ciprofloxacin-related acute peripheral neuropathy in a patient with lupus
nephritis.
AB - Ciprofloxacin is a commonly prescribed antibiotic, and drug-related peripheral
neuropathy is a rare side effect. A woman with lupus nephritis on high-dose
prednisone presented with acute peripheral neuropathy within 2 days of starting
ciprofloxacin for a urinary tract infection. Nerve conduction and
electromyographic studies confirmed a predominantly sensory, bilateral, lower
extremity neuropathy with mild motor nerve involvement. At initial presentation,
it could not be determined whether neuropathy was secondary to lupus or related
to ciprofloxacin. Based on the temporal association of drug initiation and the
onset of neuropathy, ciprofloxacin was discontinued. Her symptoms resolved within
2 weeks of ciprofloxacin discontinuation despite a simultaneous reduction in
prednisone. The short duration of the peripheral neuropathy, the absence of lupus
flare at the time of presentation, and the remission of symptoms during the
prednisone taper all strongly suggest a rare but serious neuropathic adverse
effect from ciprofloxacin. Ciprofloxacin neuropathy must be considered in
patients with lupus who present with neuropathic symptoms after initiation of
this commonly used antibiotic.
PMID- 17041344
TI - Fungal arthritis of the knee caused by Candida parapsilosis in a kidney
transplant recipient.
AB - Fungal arthritis is a rare infection usually caused by Candida species. Candida
parapsilosis has emerged as a new pathogen and has been implicated in several
cases of fungal arthritis, mostly associated with a joint prosthesis or after
arthrocentesis. We report an unusual case of fungal arthritis of the knee caused
by this organism in a 38-year-old female kidney transplant recipient, who had no
previous invasive procedures on her knee. Systemic and intraarticular antifungal
therapy combined with surgical debridement proved to be an effective treatment of
this clinically difficult condition. To our knowledge, this case is the first
report of fungal arthritis caused by C. parapsilosis in a transplant recipient.
The multimodality approach used in the treatment of this patient should be
considered in similar forms of fungal arthritis in immunocompromised patients.
PMID- 17041345
TI - Churg-Strauss syndrome and pregnancy: successful treatment with intravenous
immunoglobulin.
AB - Churg-Strauss syndrome is an extremely rare disease, and even less common in
women of childbearing age. The initial management of Churg-Strauss syndrome
consists of high doses of corticosteroids. Patients with severe disease, or those
who are unresponsive to corticosteroids, usually are treated with cytotoxic
drugs. Intravenous immunoglobulin (IVIg) has become a promising, but not
completely accepted, form of treatment for systemic vasculitis that is
unresponsive to standard therapy. We present a case of a woman diagnosed with
Churg-Strauss syndrome that was refractory to corticosteroid and cyclophosphamide
treatment. When she was found to be 3 months pregnant, treatment with IVIg was
instituted with successful results. This case not only supports the beneficial
effect of IVIg in Churg-Strauss syndrome, it illustrates its successful use in a
patient who was pregnant.
PMID- 17041346
TI - Catastrophic antiphospholipid syndrome: proposed guidelines for diagnosis and
treatment.
AB - The term "catastrophic" antiphospholipid syndrome (APS) was introduced to define
an accelerated form of APS resulting in multi-organ failure. Although patients
with the catastrophic form represent less than 1% of all patients with APS, they
are usually in a life-threatening medical situation that requires high clinical
awareness. In this article, we propose guidelines for the diagnosis and treatment
of patients with catastrophic APS, based on the cumulated published experience of
130 cases with this syndrome. We believe that it is essential that this syndrome
should be diagnosed early and treated aggressively. The combination of high doses
of heparin and corticosteroids plus intravenous gamma globulins or plasmapheresis
is proposed as the treatment of choice in patients with this severe condition. In
addition, preventive measures in patients with APS may be effective to avoid the
development of catastrophic APS. We recommend that these proposed guidelines be
tested in future prospective, collaborative studies to assess clearly the real
prevalence and the best therapy for this life-threatening condition.
PMID- 17041347
TI - The bone and joint decade 2000-;2010.
PMID- 17041348
TI - Osteoporotic vertebral compression fracture causing neurologic deficit.
AB - Osteoporotic vertebral fractures rarely cause neurologic deficits. We discuss a
69-year-old man who presented with the signs of impaired function of the left L5
nerve root. Imaging revealed a fracture of the posterior upper edge of the fifth
lumbar vertebra with a bony fragment protruding into the spinal canal. The
fracture was attributed to sneezing and coughing in this man with osteoporosis
secondary to hypogonadism. Literature search revealed 64 cases of neurologic
deficit associated with osteoporotic vertebral fracture. Most osteoporotic
fractures with neurologic deficit (72%) occur at the thoracolumbar junction. The
symptomatology of girdle-like pain and hypesthesia is not specific and may be
misinterpreted as an abdominal problem or renal pain. A typical sign is the
slowly progressive neurologic deficit, occurring spontaneously or after minor
trauma such as a fall on the buttocks. Surgical treatment confirms the diagnosis
and usually leads to remission of the neurologic signs. With increasing frequency
of osteoporotic fractures in the developed world because of the expanding elderly
population, cases with neurologic problems become more important.
PMID- 17041349
TI - Molecular biology and immunology for clinicians 18: Heat shock
proteins/chaperonins.
AB - Heat shock proteins are a highly conserved set of families of proteins produced
after a variety of stresses, both pathologic and physiologic. They are made by
all living cells; all cells use basically the same mechanisms to deal with
profound stresses. The second remarkable feature of the heat shock proteins is
that their sequence and structure are remarkably conserved across broad stretches
of evolutionary history: from Escherichia coli to Homo sapiens, heat shock
proteins have not changed a lot! Finally, as alluded to previously, heat shock
proteins are involved in physiologic functions as well, such as keeping hormonal
and antigen receptors and cell cycle-related proteins in their appropriate state
of readiness or inactivity, awaiting the ligand that will activate them.
Polypeptide chains emerge from the ribosome as a straight chain that then assumes
a tertiary structure (e.g., alpha helices, beta-pleated sheets, disulfide and
hydrogen bonds). The process of folding into this final structure may require
help because the required tertiary structure may not be the one into which the
polypeptide chain would fold if left to its own devices. Scaffolding may be
needed to coax the polypeptide to fold into its proper functional final
structure, which may not be the morphology most thermodynamically favored. The
polypeptide chain contains a series of potentially interactive surfaces (with
other sections of the polypeptide or with other proteins in the cell), just as a
receptor has at least one potentially interactive surface. Heat shock proteins
guard these potentially interactive surfaces from unwanted interactions with
extraneous and irrelevant "suitors" and may help coax the protein into the
desired interaction. The alternative to this assistance may be that the protein
folds into a useless blob or a shape that is not optimal for its intended use;
such misfolded proteins are degraded by normal housekeeping functions of the
cell. The highly conserved nature of heat shock proteins means that the immune
response to heat shock proteins of pathogens or malignant cells may recognize and
then react with host heat shock proteins and produce autoimmune disease.
PMID- 17041351
TI - Ulcerating skin lesions and arthritis after a crab bite.
PMID- 17041353
TI - Cutaneous vasculitis and antiphospholipid syndrome in a patient with ankylosing
spondylitis: how may they be related?
PMID- 17041356
TI - Question about coexisting lyme disease and parvovirus infection.
PMID- 17041354
TI - Cerebrovascular disease in systemic lupus erythematosus (SLE): lack of
association with anticardiolipin (aCL) antibodies.
PMID- 17041357
TI - It's a dirty job but someone has to do it: thoughts about mud and other
complementary and alternative therapies.
PMID- 17041358
TI - Central nervous system compromise in primary Sjogren's syndrome.
AB - Central nervous system (CNS) involvement in primary Sjogren's syndrome (SS) is
poorly understood, and its frequency as well as its manifestations are subjects
of controversy. The current study was undertaken to determine the prevalence and
the clinical and immunogenetic characteristics of CNS compromise in a well
defined group of patients with primary SS. In this retrospective study, patients
fulfilled the European classification criteria. Among 120 patients with primary
SS, 3 (2.5%) had CNS compromise (multiple sclerosis-like illness, complicated
migraine, and optic neuritis with epilepsy). The CNS involvement coincided with
the onset of sicca symptoms in 1 case. All 3 patients carried the human leukocyte
antigen (HLA) DQB1*0303 allele and tested positive for anti-Ro antibodies, but
not for anti-cardiolipin antibodies. Although rare, CNS compromise in primary SS
can be the presenting manifestation of the disease in a few cases, and may be
severe and varied.
PMID- 17041359
TI - Therapy with mud compresses for knee osteoarthritis: comparison of natural mud
preparations with mineral-depleted mud.
AB - Mud pack therapy is an alternative mode of treatment for rheumatic diseases. It
is based on the application of heated mud packs to the entire body or to specific
areas, such as over joints. The aim of the current study was to evaluate the
efficacy of treatment with mud compresses at patients' homes for osteoarthritis
of the knee. Fifty-eight patients with osteoarthritis of the knee were enrolled
in a prospective, double-blinded, controlled study. Forty patients were treated
with natural mineral-rich mud compresses and 18 patients were treated with
mineral-depleted mud compresses. Mud compresses were applied 5 times each week
during 3 weeks for a total of 15 treatments. Patients were assessed at baseline,
at completion of the 3-week treatment period, and twice after the conclusion of
the treatment period-after 1 month and after 3 months. The main outcome measures
were the Lequesne Index of severity of knee osteoarthritis, patient self
assessment of pain, and severity of knee pain on a visual analog scale. A
reduction of 20% or more in the pain scores was considered clinically
significant. In the group treated with natural mud compresses, a significant
reduction in knee pain was observed at all assessments. Similarly, improvement in
the Lequesne Index was seen at the end of therapy and a month after treatment. In
the control group, given mineral-depleted mud compresses, no significant change
in knee pain was seen at any assessment. Improvement in the Lequesne Index was
seen 1 and 3 months after completion of the therapy, but not at the end of
therapy. Seventy-two percent of the patients in the treatment group had an
improvement of >20% in self-assessment of knee pain, compared with 33% in the
control group (p = 0.005). The data suggest that treatment with mud compresses,
but only in their natural form, temporarily relieves pain in patients with
osteoarthritis of the knees. We believe that treatment with mud compresses might
augment conventional medical therapy in these patients.
PMID- 17041361
TI - Transient elevation of the tumor markers CA 15-3 and CASA as markers of
interstitial lung disease rather than underlying malignancy in dermatomyositis
sine myositis.
AB - A 37-year-old woman with severe interstitial lung disease associated with
dermatomyositis sine myositis is reported. A thoracoscopic lung biopsy revealed
organizing diffuse alveolar damage. Significantly elevated serum levels of the
tumor markers CA 15-3 and CASA (cancer-associated serum antigen) were detected,
but no evidence of an underlying malignancy (including breast and ovarian) was
found on serial clinical and radiologic examinations. These levels gradually
normalized as the interstitial lung disease responded to a combination of
cyclophosphamide and corticosteroids. The use of the CA 15-3 and CASA assays to
measure serum levels of the highly glycosylated, high-molecular-weight mucin MUC1
in interstitial lung disease has not been previously described. Clinicians should
therefore be aware that elevation of these tumor markers may reflect the presence
of interstitial lung disease rather than an underlying malignancy in patients
with dermatomyositis, especially if the levels normalize after successful
treatment of the lung disease.
PMID- 17041363
TI - Sudden death in rheumatoid arthritis: pulmonary embolism--a fatal complication of
iliopsoas bursitis.
AB - Sudden death resulting from embolic complications of iliopsoas bursitis has not
been previously reported. This case report deals with a 48-year-old woman with
seropositive rheumatoid arthritis who presented with symptoms suggestive of deep
vein thrombosis. She was found to have complete occlusion of the femoral vein
secondary to iliopsoas bursal inflammation and swelling. She died suddenly. At
autopsy, a large pulmonary embolism was identified as the cause of death. This
report should increase awareness of the incidence of iliopsoas bursitis in
rheumatoid arthritis and its potential danger. Early and aggressive management
approaches described herein might have prevented this fatality.
PMID- 17041365
TI - Paget's disease of bone in an Indian patient: genetic and environmental factors.
AB - Epidemiologic data have shown that Paget's disease of bone is common among people
of Anglo-Saxon descent, but it is believed to be rare in India and Asia. The
worldwide prevalence of the disease shows pronounced geographic and ethnic
heterogeneity, and can vary in populations through migration or loss of
geographic isolation. The risk to an individual who changes geographic locations,
however, is difficult to quantify because the specific genetic or environmental
factors responsible for Paget's disease have yet to be completely determined. We
describe a case of monostotic Paget's disease in a 59-year-old Asian Indian man,
and consider the potential epidemiologic and etiologic influences (moving to an
area of higher disease prevalence, role of genetics, viral exposures) that may
have increased his risk for the disorder. The patient presented with several
months of right anterior leg pain, and was found on examination to have anterior
bowing of the tibia as well as warmth and an audible bruit. Radiographs of the
tibia demonstrated a V-shaped lucency, enhanced trabecular pattern, and cortical
thickening. Whole-body bone scan confirmed monostotic disease with expansile
uptake in the tibia, and laboratory data revealed an elevated urinary collagen N
telopeptide that normalized after bisphosphonate treatment, as did his clinical
symptoms. In light of the environmental factors that appear significantly to
influence the development of Paget's disease, the diagnosis should be considered
in patients traditionally considered at low risk for the disorder.
PMID- 17041367
TI - Fatal cytomegalovirus infection in two patients with systemic lupus erythematosus
undergoing intensive immunosuppressive therapy: role for cytomegalovirus
vigilance and prophylaxis?
AB - Cytomegalovirus (CMV) infection is an uncommon but potentially fatal
opportunistic infection in patients with systemic lupus erythematosus (SLE). We
report 2 patients with severe SLE with life-threatening, multisystemic
involvement who were treated with intensive immunosuppressive therapy. SLE was
successfully controlled, but the patients succumbed to fatal reactivation of CMV
disease despite antiviral therapy. Both were seropositive for CMV. We therefore
advocate that there should be more active CMV vigilance, and polymerase chain
reaction (PCR)-based CMV prophylaxis should be considered in CMV PCR-positive
patients with SLE/rheumatic disease undergoing intensive immunosuppressive
therapy.
PMID- 17041368
TI - Upcoming international meetings.
PMID- 17041370
TI - Molecular biology and immunology for clinicians 19: Protein purification and
synthesis technology.
AB - Everywhere one looks in the practice of medicine there is the need to understand
things at the level of specific proteins: vaccine design using a single protein
would be much safer and efficient than the whole organism; diagnostic tests would
be less prone to false-positive results if a single protein could be used; and on
and on. The DNA revolution allowed us to manipulate the specific genes making
proteins of interest, leading to the ability to make single proteins, called
recombinant proteins, in inexhaustible supply. And now we can make chimeric
proteins, like the mythical animal, with the head of one protein, the tail of
another, and perhaps the body of a third--as many components as you like, the sky
is the limit.
PMID- 17041371
TI - A case of multicentric reticulohistiocytosis initially misdiagnosed as lupus.
PMID- 17041369
TI - Isolated digital gangrene complicating hepatitis a infection in a child.
AB - Hepatitis A virus is rarely associated with extrahepatic complications. A child
presented with a history suggesting Raynaud's phenomenon and severe digital
gangrene, as a complication of hepatitis A infection. Coagulation study results
(protein C, protein S, antithrombin III, and activated protein C resistance) were
all normal except for anticardiolipin antibodies, which were present on initial
presentation and resolved later. Antinuclear antibodies, rheumatoid factor, lupus
anticoagulant, antineutrophilic cytoplasmic antibodies, and Venereal Disease
Research Laboratory test were all negative. Cryoglobulins were not detected. C3
and C4 levels were normal. Blood urea nitrogen and creatinine levels were normal
as well. The patient was treated with aspirin and diclofenac, and improved slowly
with complete resolution of gangrene and symptoms after 3 months. She remains
asymptomatic 4 years later. Transient antiphospholipid syndrome or isolated
Raynaud's phenomenon may be added to the list of extrahepatic complications of
hepatitis A.
PMID- 17041372
TI - Why are all these rows of joints involved?
PMID- 17041374
TI - Combined antibiotic therapy of post-venereal reactive arthritis.
PMID- 17041375
TI - Minimally-invasive salivary gland biopsy technique.
PMID- 17041376
TI - Ethnic differences in male lupus.
PMID- 17041377
TI - Are monoclonal gammopathies in rheumatoid arthritis predictive for
lymphoproliferative disorders?
AB - There is limited evidence for the association of specific malignancies with
rheumatoid arthritis (RA). Monoclonal gammopathies can occur in RA. Their
predictive value for the development of a lymphoproliferative disorder remains
unclear and disputed. We reviewed charts of 214 RA patients all of whom had at
least one serum protein electrophoresis. We performed a retrospective study of 12
patients with RA and an M spike. We further characterized the M spike by serum
immunofixation and bone marrow studies. The median age at which the M spike was
identified was 69 years. IgG was the predominant gammopathy in 50% of patients,
with no difference in the amount of kappa (kappa) and lambda (lambda) chains. One
patient was diagnosed with multiple myeloma, one with an undefined primary
lymphoproliferative disorder, one with T-cell leukemia, five with myelodysplastic
syndrome, and four with monoclonal gammopathy of undetermined significance at
most recent evaluation. Of our patients, 42% had a myelodysplastic syndrome,
which has not been previously reported, and, in contrast to previous reports, no
lymphomas were identified. The follow-up evaluation of patients with
myelodysplastic syndrome and monoclonal gammopathy of undetermined significance
is important because they may progress to an overt neoplasia.
PMID- 17041378
TI - Cardiopulmonary exercise testing with pulmonary artery catheterization detects
early pulmonary vasculature changes in patients with connective tissue diseases.
AB - Pulmonary hypertension is a well-recognized complication of connective tissue
diseases (CTD), with clinical symptoms typically limited to those with relatively
advanced disease. The objective of this study was to identify patients with early
pulmonary vasculature changes using cardiopulmonary exercise testing with
pulmonary artery catheterization. Four patients with CTD and normal Doppler
echocardiogram results identified as high risk for pulmonary hypertension on the
basis of disease process underwent cardiopulmonary exercise testing with
pulmonary artery catheterization. All patients had normal mean pulmonary artery
pressures at rest (<25 mmHg), but exhibited an abnormal rise in mean pulmonary
artery pressure with exercise. Cardiopulmonary exercise testing should be
considered in patients at high risk for pulmonary hypertension to identify those
individuals who may benefit from early therapeutic intervention.
PMID- 17041380
TI - Antiprothrombin antibodies in patients with systemic lupus erythematosus or with
primary antiphospholipid syndrome.
AB - Some authors have found a strong statistical association of antibodies to
prothrombin (aPT) with thrombosis in patients with antiphospholipid syndrome
(APS); others have not confirmed this finding. It is unknown if the detection of
aPT, in addition to anticardiolipin (aCL) and anti-beta2-glycoprotein-I (abeta2GP
I) antibodies, provides additional information in the clinical study of these
patients. We studied 38 patients with primary antiphospholipid syndrome and 466
patients with systemic lupus erythematosus (SLE; 24 had a history of thrombosis
and 69 had secondary APS). All were tested by ELISA for serum aPT (IgG and IgM)
using irradiated and plain plates. We also detected aCL and anti-beta2GP-I by
ELISA. One hundred sera from clinically healthy individuals were used as
controls. Twenty-six percent and 11% primary APS sera were positive for IgG and
IgM aPT, respectively, compared with 3% and 5% of controls (p < 0.001, both
comparisons). We found no difference in the frequency of aPT in SLE patients and
controls, but aPT were positive in 46% of lupus patients with a history of
thrombosis (20% IgG, 33% IgM) and in 9% of those without thrombosis (6% IgG, 5%
IgM; p < 0.001, both comparisons). Likewise, there was a significant difference
in the frequency of aPT in SLE patients with (22%) or without (9%) secondary APS
(p < 0.001). aPT titers decreased two- to sixfold when tested in plain plates.
Thirty-five of 38 primary APS sera (92%) had IgG anti-beta2GP-I and 12 (31%) had
aCL. No patient had aPT as the only antibody. The higher binding of aPT on
irradiated plates suggests that aPT recognize a hidden epitope exposed by
negative surfaces. The higher frequency of aPT found in patients with primary
APS, SLE with thrombosis, or with secondary APS may suggest concerted pathogenic
actions with other autoantibodies, but the detection of aPT does not seem to be
of clinical value.
PMID- 17041381
TI - Successful treatment of idiopathic febrile panniculitis (Weber-Christian disease)
with thalidomide in a patient having failed multiple other medical therapies.
AB - The authors describe a case of idiopathic nodular panniculitis (Weber-Christian
disease) with recurrent febrile episodes resistant to glucocorticosteroids and
methotrexate (MTX) in various combinations with hydroxychloroquine, azathioprine,
cyclosporine, colchicine, and doxycycline. Thalidomide at 100 mg/day has induced
a remission for 3 years.
PMID- 17041382
TI - Pulmonary artery involvement in Takayasu's arteritis with lung infarction and
pulmonary aspergillosis.
AB - We describe a patient with a chronic case of pulmonary involvement of Takayasu's
arteritis in the resected lung. A 49-year-old woman was first diagnosed with
Takayasu's arteritis at age 30 years. On her first admission, she presented with
Takayasu's arteritis and pneumonia with cavitation in the left lung. After
recovering from pneumonia, she was treated initially with prednisolone, 30
mg/day, and remained well until she developed hemoptysis at age 34 years.
Findings suggesting aspergilloma were found in the same lobe on chest x-ray film
when she was 46 years of age. By age 49 years, the hemoptysis became massive, and
she was admitted for surgery. Left upper lobectomy and partial resection of S6
and S8 pulmonary segments were performed. Histologic analysis of the resected
lung revealed typical pathologic findings of pulmonary artery involvement in
Takayasu's arteritis, such as stenosis recanalization and a vessel-in-vessel
feature, but not active vasculitis. Infection probably occurred in the cavity of
the infarcted tissue. Pulmonary artery involvement is common in Takayasu's
arteritis, but the aspergilloma in this corticosteroid-treated patient is an
uncommon complication.
PMID- 17041383
TI - Mycobacterium marinum tenosynovitis in a patient on etanercept therapy for
rheumatoid arthritis.
AB - Opportunistic infections are a theoretical concern with the use of tumor necrosis
factor antagonists, as these agents can impair host immunity. A 61-year-old man
with rheumatoid arthritis being treated with only etanercept (soluble tumor
necrosis factor receptor) and in remission from the rheumatoid arthritis
presented with dorsal tenosynovitis of his right wrist. The synovitis was not
improved by a local corticosteroid injection. Surgical exploration showed
granulomatous inflammation, and cultures were positive for Mycobacterium marinum
infection. Etanercept was discontinued 4 months after the hand infection started.
The infection resolved completely with surgery and antibiotic therapy with
clarithromycin 500 mg twice daily orally for 3 months. Although M. marinum
infection was locally invasive, there was no systemic dissemination of the
infection despite ongoing etanercept therapy for 4 months before it was
discontinued. With more frequent use of this class of agents for rheumatoid
arthritis and Crohn's disease, we caution physicians to be alert for the
possibility of this kind of local opportunistic infection.
PMID- 17041384
TI - Myasthenia gravis in a patient with pauciarticular juvenile chronic arthritis.
AB - There have been reported cases of children with histories of pauciarticular
juvenile chronic arthritis (JCA) later developing myasthenia gravis (MG) as young
adults. This is intriguing because it had been considered rare to diagnose a
second autoimmune disease in a patient with pauciarticular JCA, unlike in those
with adult-onset rheumatoid arthritis. We report a case of MG in a 20-year-old
woman with a history of pauciarticular JCA. She presented with bilateral ptosis,
weakness, and a history of dysphagia. The diagnosis was confirmed with positive
serum acetylcholine receptor antibodies (2000 nm/L) and electromyography showing
a decremental response to repetitive muscle stimulation. The patient's
inflammatory arthritis was quiescent at diagnosis. The patient underwent a
surgical thymectomy and was treated with pyridostigmine, intravenous
immunoglobulin, and corticosteroids with a fluctuating clinical course. Previous
cases have been reported of MG associated with this subtype of JCA, suggesting a
connection in autoimmune pathology. The earlier recognition and management of MG
in a patient with pauciarticular JCA presenting with weakness may improve the
prognosis of this disease.
PMID- 17041385
TI - Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome)
associated with hypogammaglobulinemia and elevated serum tumor necrosis factor
alpha levels.
AB - Pyogenic aseptic arthritis, pyoderma gangrenosum, and cystic acne (PAPA) syndrome
is an unusual triad that was recently mapped to a chromosome 15q mutation. We
describe a patient from this kindred in whom hypogammaglobulinemia and elevated
tumor necrosis factor-alpha serum levels were detected. The patient responded
well to intravenous gammaglobulin and intra-articular corticosteroid therapy.
Immune abnormalities can be found in PAPA syndrome and could be the consequence
of the chromosomal abnormalities affecting candidate genes on this chromosome
with subsequent abnormalities in cytokine or chemokine secretion. Rheumatologists
should be alert for this syndrome. Correction of the immune abnormalities may be
effective in controlling the disease manifestations.
PMID- 17041386
TI - Thrombotic microangiopathy in a patient with adult onset Still's disease.
AB - We report a case of a 23-year-old man with adult onset Still's disease (AOSD)
developing a rare, life-threatening complication of thrombotic microangiopathy
(TMA). While the AOSD was in an active phase, our patient first developed
hemolytic uremia syndrome, soon followed by convulsions, sudden loss of vision,
and thrombotic angiopathy of retinal vessels. After immediate and aggressive
treatment with high dose prednisolone and 18 courses of plasmapheresis, he
recovered from this severe complication. We think that the occurrence of TMA in
AOSD may not be coincidental, although more reports are needed to support this.
Early recognition and aggressive immunotherapy can allow patients with AOSD to
completely recover from this life-threatening complication.
PMID- 17041389
TI - An unusual synovial fluid as a clue to a cause of ankle monoarthritis.
PMID- 17041387
TI - Molecular biology and immunology for clinicians 20: Angiogenesis and vascular
growth factors and signals.
AB - If we accept the perfectly reasonable premise that the mass of inflammatory
tissue in rheumatoid arthritis (and psoriatic arthritis or any other inflammatory
joint disease) requires oxygen and nutrition to survive and grow, we are
confronted with a novel concept for therapy: if we can block the nutritional
supply of the pannus, we can suppress or prevent its growth and the subsequent
destruction of the joint. Thus, an understanding of how new blood vessels nourish
the inflammatory mass could be pivotal in successfully treating our patients.
Angiogenesis is the process whereby new blood vessels enter the site of
inflammation or growing malignancy to supply the invading tissue. Many growth
factors and local tissue conditions help to determine blood vessel growth, there
being pro- and anti-angiogenetic influences. Thus, this is fertile ground for
therapeutic molecular manipulations.
PMID- 17041391
TI - Leflunomide in psoriatic polyarthritis.
PMID- 17041392
TI - Implication of occult alveolar hemorrhage in Henoch-Schonlein purpura.
PMID- 17041394
TI - Is coadministration of alendronate and nonsteroidal antiinflammatory drugs an
unacceptable risk?
PMID- 17041395
TI - Acute hip monoarthritis in systemic lupus erythematosus.
PMID- 17041396
TI - Postmarketing surveys: up sides and down sides.
PMID- 17041397
TI - Mini-aspirin: more facets of a tiny pill?
PMID- 17041398
TI - Effect of minidose aspirin on renal function and renal uric acid handling in
healthy young adults.
AB - Minidose aspirin (60-325 mg/day) has been widely used in the prevention and
treatment of cardiovascular and cerebrovascular diseases. However, studies on the
effects of minidose aspirin on renal handling of uric acid and renal function are
limited. We studied the effect of aspirin at 60 mg/day (n = 18) and 300 mg/day (n
= 14) on uric acid handling and renal function in healthy subjects. The subjects
were evaluated weekly during 2 weeks of aspirin therapy, and again 1 week after
aspirin was discontinued. Aspirin at both dosages decreased the fractional
excretion of uric acid. However, aspirin at 300 mg/day, but not 60 mg/day,
significantly decreased uric acid clearance and creatinine clearance by the end
of the second week of aspirin therapy. Despite these changes, serum uric acid and
serum creatinine remained constant. The uric acid clearance, but not the
creatinine clearance, returned to baseline value 1 week after aspirin therapy was
discontinued. As aspirin at 60 mg/day showed no suppressive effect on renal
function, it may be better for long-term use.
PMID- 17041399
TI - Prescription and tolerability of meloxicam in day-to-day practice: postmarketing
observational cohort study of 13,307 patients in Germany.
AB - The goal of this study was to obtain data for prescription habits, tolerability
for patients at high risk, and clinical effectiveness of meloxicam administered
at 7.5 mg and 15 mg for various rheumatic diseases under real world prescribing
conditions. This was a 3-month large-scale prospective observational cohort study
in 4000 medical practices throughout Germany shortly after the introduction of
meloxicam. To be eligible, patients had to have a diagnosis of acute or chronic
active rheumatic disease for which nonsteroidal antiinflammatory drug (NSAID)
therapy was required according to the prescribing information. In this study,
13,307 patients receiving meloxicam prescriptions (7.5 mg in 65% and 15 mg in
33%) were observed. The diagnoses of these patients included osteoarthritis
(61%), rheumatoid arthritis (24%), ankylosing spondylitis (1.6%), and other
rheumatic conditions (28%). A substantial proportion of high risk patients were
enrolled: 12% with a previous history of a perforation, ulceration, and bleeding
(PUB), 24% with at least one concomitant cardiovascular disorder, and 26%
receiving concomitant antihypertensive medication. Many of the patients (58%) had
received NSAIDs before meloxicam, including patients with insufficient prior
treatment effectiveness (43%) and those with NSAID-related adverse drug reactions
(21%). In 85% and 94% of the patients, respectively, effectiveness and
tolerability were rated as good or very good. Quality of life and daily functions
improved in 64% to 84% of the patients. Only 0.8% of the patients reported
gastrointestinal (GI) adverse drug reactions. Four uncomplicated cases of gastric
ulceration, one serious perforated gastric ulcer, and one serious ileus
complication were reported after incorrect use or overdosing of meloxicam.
Treatment with the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam in
doses of 7.5 mg and 15 mg resulted in meaningful treatment responses under real
life conditions, despite inclusion of a substantial number of patients with
insufficient effectiveness of previous use of non-COX-2 selective NSAIDs. All
major GI toxicity (PUB) observed was owing to the fact that prescribing
conditions were not respected appropriately. Despite a selection of high risk
patients overall, GI, cardiovascular, and renal tolerability was favorable.
PMID- 17041400
TI - Coronary electron beam computed tomography in 13 patients with systemic lupus
erythematosus and two or more cardiovascular risk factors.
AB - Cardiovascular and cerebrovascular events, the third leading cause of death in
patients with systemic lupus erythematosus (SLE), are disproportionately common
by age and gender. Risk factors for atherosclerotic cardiovascular disease
(ASCVD) cannot reliably predict subsets of patients at risk for events. Coronary
electron beam computed tomography (EBCT), a noninvasive imaging technique that
quantifies ASCVD by measuring calcium deposition in the walls of coronary
arteries, has been demonstrated to be a marker of ASCVD in traditional
populations. A pilot group of 13 SLE patients (ages, 33-48 years) with two or
more traditional risk factors for cardiovascular disease were studied by EBCT.
Five of these SLE patients had calcification scores in the 70th percentile or
higher, as compared with age-matched women without known coronary artery disease,
and three had scores in the 90th percentile. Four of these five patients had
antiphospholipid antibodies currently or in the past. These data suggest that
EBCT may be able to detect premature ASCVD in SLE patients and may be a useful
noninvasive tool as more attention is directed to ASCVD as a major complication
of SLE.
PMID- 17041402
TI - Coexistence of four autoimmune diseases in one patient: the kaleidoscope of
autoimmunity.
AB - Genetic, immune, hormonal, and environmental factors are associated with the
multifactorial origin of autoimmunity. When one or more of these factors are
altered, a "switch" from one autoimmune condition to another can occur,
developing the so called "kaleidoscope phenomenon" of autoimmunity. We present
the case of a 30-year-old woman with myasthenia gravis and hypothyroidism
probably resulting from autoimmune thyroiditis. A thymectomy was performed, and 1
year later, rheumatoid arthritis was diagnosed based on clinical, radiological,
and serological features. Nine years after thymectomy, systemic lupus
erythematosus was diagnosed based on skin, renal, hematologic, and immunologic
manifestations. We suggest that the immune system function was modified when
thymectomy was performed, playing an important role in the development of the new
autoimmune conditions. Thymectomy increases the risk of developing a new
autoimmune disease because it modifies, by mechanisms not well defined, the
equilibrium and normal function of the immune system. This patient presents the
infrequent association of four autoimmune conditions. When a patient has one
autoimmune disease, she is at risk for another.
PMID- 17041403
TI - Widespread cutaneous necrosis associated with antiphospholipid antibodies: report
of four cases.
AB - We describe four patients with widespread cutaneous necrosis as a manifestation
of the antiphospholipid antibody syndrome. In three of the patients, the lesions
were the first manifestation of the syndrome, and they were located in upper and
lower extremities. Vascular thrombosis was present in the skin biopsy in all of
the patients. Patients were effectively treated with anticoagulants, and healing
occurred within 60 days. Such widespread cutaneous necrosis is a rare
manifestation of the syndrome, and it must be regarded as major thrombotic event.
Long-term treatment with anticoagulants must be considered. The recognition of
these lesions is important, because they may be the onset of the syndrome,
allowing its early diagnosis and treatment.
PMID- 17041404
TI - Chorea and rapidly progressive subcortical dementia in antiphospholipid syndrome.
AB - Antiphospholipid antibodies are associated with a variety of neurologic
manifestations, both in patients with and without concomitant systemic lupus
erythematosus. We report a patient in whom chorea and rapidly progressive
subcortical dementia developed in the setting of persistently high titers of
antiphospholipid antibodies. While some manifestations of antiphospholipid
syndrome can be clearly linked to vascular thrombosis, it is not known whether
this is also true for patients affected with chorea, dementia, or both. In our
patient, serial magnetic resonance imaging showed the progressive development of
deep white matter lesions but no cortical infarcts. The development of widespread
pulmonary arterial thrombosis and acute cerebral ischemia, evidenced clinically
and on diffusion-weighted magnetic resonance imaging of the brain, provided
indirect evidence for a thrombotic pathogenesis for this patient's neurologic
disease. Anticoagulation should be considered as an adjunct to the treatment of
patients with antiphospholipid antibodies and chorea or subcortical dementia.
PMID- 17041405
TI - Shrinking lung syndrome in systemic lupus erythematosus and Sjogren's syndrome.
AB - Shrinking lung syndrome (SLS) is a rare complication of systemic lupus
erythematosus (SLE) characterized by unexplained dyspnea, a restrictive pattern
on pulmonary function tests, and an elevated hemidiaphragm. A total of 59 cases
are reported in literature including the current case. The mean age of these
patients is 36.85 years (range, 15-61 years), and the female-to-male ratio is
6:1. This disorder is seen primarily during the later stages of SLE. The most
common presenting features include dyspnea and pleuritic chest pain. Myositis has
been reported in only 8 of 59 patients (13%). Diagnosis is made with chest x-ray
showing an elevated hemidiaphragm and a restrictive pattern on pulmonary function
testing without any evidence of interstitial lung disease along with decreased
transdiaphragmatic pressure (Pdi). Corticosteroids are the most common method of
treatment. Immunosuppressive therapy, beta-agonists, and theophylline are used in
those resistant to steroids. The prognosis is generally good. This article
reports the case of a 22-year-old man presenting with a 7-month history of dry
mouth and dry eyes accompanied by increasing difficulty in breathing, progressing
to dyspnea at rest. The patient's history included bilateral parotid gland
swelling and nephrotic syndrome diagnosed 4 years earlier. Pertinent physical and
laboratory findings included positive Schirmer's test results; bilateral parotid
gland enlargement; bibasilar lung crackles; synovitis of the second and third
proximal interphalangeal joints; a positive antinuclear antibody (Ro/SSA), Sm,
and anticardiolipin antibodies; and elevated right hemidiaphragm on chest x-ray.
Pulmonary function tests demonstrated restrictive lung disease with normal high
resolution computerized axial tomography. A dramatic response to oral prednisone
(60 mg daily) was observed in all of the patient's complaints in a matter of
several days. A diagnosis of SLE with secondary Sjogren's syndrome (SS) and SLS
was made. Although SLS has been reported in association with SLE, there has been
only one previous report of SLS in SLE/SS overlap syndrome. Early recognition
with appropriate treatment can decrease the morbidity associated with this rare
syndrome.
PMID- 17041406
TI - Intramuscular bleeding as a complication of anticoagulation treatment in a
patient with systemic lupus erythematosus and antiphospholipid syndrome.
AB - Thrombotic events account for significant morbidity and mortality among patients
with antiphospholipid syndrome. The cornerstone of management includes long-term
anticoagulation. However, the benefit of long-term anticoagulation must be
weighed against the risk of bleeding complications. This article presents the
case of a patient with systemic lupus erythematosus and antiphospholipid syndrome
who experienced severe intramuscular hemorrhage as a complication of warfarin
anticoagulation. This case emphasizes the importance of careful monitoring of
anticoagulation treatment, and of recognizing a new differential diagnosis when
dealing with a painful, swollen calf in the setting of lupus and antiphospholipid
syndrome.
PMID- 17041407
TI - Molecular biology and immunology for clinicians 21: The innate immune system: an
introduction.
AB - The human (mammalian) immune response includes two interrelated but separable
components: the innate immune system and an adaptive immune response. The former
constitutes the sole immune defense strategy of invertebrates. It is only with
vertebrate evolution that an adaptive immune response, first cellular, then later
humoral, develops. Recent studies and a reconsideration of the innate system
allow a fuller appreciation of its complexities, unique qualities, and
irreplaceable value. In the early days of an infection, long before an effective
adaptive immune response can be mounted, the innate system puts up an effective
defense. Innate systems provide the costimulatory signal needed to unleash the
adaptive immune response. Future contributions to this series will provide
details about some of the specific innate immune systems. This article serves as
an introduction to this underappreciated (until recently) aspect of human immune
defenses.
PMID- 17041410
TI - Comment on bone mineral density and bone turnover markers in a group of male
ankylosing spondylitis patients.
PMID- 17041411
TI - Cholangiocarcinoma in a patient on long-term methotrexate: are there theoretical
reasons for its occurrence?
PMID- 17041412
TI - Clinical aspects of combined cyclosporin a and leflunomide therapy in rheumatoid
arthritis.
PMID- 17041413
TI - Small vessel vasculitis in Takayasu's arteritis.
PMID- 17041414
TI - Fasciitis: what is the significance of various forms?
PMID- 17041415
TI - The managed care versus fee for service dilemma and its impact on the outcome of
lupus.
PMID- 17041416
TI - Outcome of chilean patients with lupus nephritis and response to intravenous
cyclophosphamide.
AB - Several recent open studies suggest that the response rates of lupus nephritis to
intravenous (IV) cyclophosphamide are lower than those observed in clinical
trials. One explanation could be ethnic differences; for example, black patients
more frequently have treatment-resistant lupus nephritis. Another could be the
inclusion of patients who are noncompliant with therapy. From our register of 268
systemic lupus erythematosus (SLE) patients examined between 1973 and 1996, 61
patients were treated for proliferative lupus nephritis (17 had World Health
Organization [WHO] type III and 43 had WHO type IV) and were followed through to
2001. Exclusion criteria included a serum creatinine level >3 mg/dL. In this
retrospective study, we assessed renal outcome and survival with an endpoint of
end-stage renal disease (ESRD) or death (Kaplan-Meier). In the univariate
analysis, worse prognostic factors for survival were serum creatinine >1.3 mg/dL
(p < 0.001), age <30 years (p < 0.001), class 2 renal function stage (p < 0.03),
and renal biopsy activity index >7 (p < 0.02). In the subgroup of 26 patients
treated with IV cyclophosphamide, survival at 5 and 10 years was 82% and 73%,
respectively. The dosage of IV cyclophosphamide was slightly lower than usual and
used for a shorter period (median = 23 months) than what is usually recommended
because of the high frequency of complications. Renal outcome of the IV
cyclophosphamide-treated patients was poorer than that reported in the National
Institutes of Health series (ESRD: 15% versus 3%). This low survival rate could
reflect the short course and lower doses of IV cyclophosphamide used or ethnic
differences. These data emphasize the need for continuous research for better
tolerated drug schemes for treatment of our lupus nephritis patients.
PMID- 17041417
TI - An overview of the use of computers in clinical rheumatology: models of care for
the next millennium.
AB - Practitioners of rheumatology in the 21st century are increasingly recognizing
the benefits of computer technology as they relate to point-of-service care
delivered in the hospital or in the outpatient setting. Electronic medical
records and other computer-driven aids are resources emerging as affordable tools
that can greatly enhance the rheumatologist's ability to provide stellar care,
reduce professional and administrative burdens and improve lifestyle measures.
Herein, we provide a practical nontechnical introduction to the world of
electronic medical records, personal digital assistants, and other computer
dependent tools, with an emphasis placed on how these instruments can be used by
the clinical rheumatologist to achieve excellence in medical care.
PMID- 17041418
TI - Impact of managed care on clinical outcome of systemic lupus erythematosus in
Puerto Rico.
AB - This study was designed to explore the impact of a managed care system on the
morbidity and mortality rates in a systemic lupus erythematosus (SLE) cohort in
Puerto Rico. The clinical manifestations and outcome measures of public SLE
patients, before and after implementation of the managed care system, were
compared with those of SLE patients treated in a private fee-for-service system.
Of the cohort of 171 patients, 103 (60%) were treated in the public system and 68
(40%) in the private sector. Except for higher prevalence of hematuria, renal
insufficiency, and serositis in the public group, both groups had a similar
prevalence of clinical manifestations, Systemic Lupus Erythematosus International
Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage score,
and mortality rate before introduction of the managed care system. Six years
after implementation of the managed care system, medically indigent patients were
more likely to have photosensitivity (90% vs. 75%), malar rash (85% vs. 65%),
hematuria (43% vs. 24%), nephrotic syndrome (17% vs. 6%), and end-stage renal
disease (8% vs. 0%). They also had a higher mortality rate (10% vs. 2%) and
SLICC/ACR damage index score (1.5 vs. 0.8). In summary, SLE patients treated in
the public system of Puerto Rico demonstrated higher morbidity and mortality
after being treated in a managed care system compared with patients managed in a
private fee-for-service system. Different from the fee-for-service system, the
managed care system seeks medical care cost reductions that could affect the
management and outcome of SLE patients. These differences could also be related
to the higher disease severity before implementation of the managed care system
and lower socioeconomic status of the public group. Nevertheless, the public
managed care system in Puerto Rico requires continuous evaluation to ensure SLE
patients better access to specialty and subspecialty healthcare and optimal
pharmacologic treatments.
PMID- 17041419
TI - Fasciitis after allogeneic peripheral blood stem cell transplantation in a
patient with chronic myelogenous leukemia.
AB - Fasciitis, one of the presentations of chronic skin graft-versus-host disease
(GVHD), is characterized by symmetrical inflammatory swelling of extremities with
or without eosinophilia, but it is rarely reported. This article describes a
patient with the clinical and histologic features of fasciitis, as the only form
of chronic GVHD that developed 20 months after HLA-matched allogeneic peripheral
hematopoietic stem cell transplantation (HSCT) for chronic myelogenous leukemia
(CML). She reported tightness of the skin and pain in both wrists and elbows on
motion, with edema of the limbs. A deep cutaneous biopsy showed thickening of the
subcutaneous fascia with inflammatory infiltrates. The patient was treated with
cyclosporine and prednisone, which resulted in much improvement of her symptoms
and signs related to the fasciitis. The authors recommend that clinicians
maintain a high index of suspicion for fasciitis because fasciitis is a distinct
entity among the chronic GVHD that may lead to a functional disability.
PMID- 17041420
TI - Inflammatory arthritis associated with thromboangiitis obliterans.
AB - Thromboangiitis obliterans (TAO) is an uncommon to rare vasculitis of small and
medium arteries and veins typically affecting young male smokers. Inflammatory
arthritis has only been rarely reported in association with TAO. We describe the
case of a young male smoker presenting with inflammatory arthritis as the initial
manifestation of his TAO. His arthritis resolved with a course of corticosteroid
therapy. The vascular disease improved with hyperbaric oxygen therapy, although
he continued to smoke. Similar cases have been described, suggesting that
rheumatologists should keep Buerger's disease in mind in patients with arthritis
and vascular disease.
PMID- 17041421
TI - Blister as the initial presentation of gout.
AB - We present a case of gout that presented initially as a bullous lesion. The
patient had no history of gout, and the lesion was diagnosed initially as a
simple pressure sore. Examination revealed a large blister over the right medial
first metatarsophalangeal joint. Aspiration of the blister yielded cloudy fluid,
with many monosodium urate crystals present on microscopic examination. There is
scant literature on bullous lesions in gout. Such lesions can occur in patients
known to have gout or can lead to the diagnosis of gout in previously undiagnosed
patients. Gouty blisters likely form at sites of trauma, as has been proposed for
gouty tophi. This case also emphasizes the importance of careful clinical and
microscopic examination of aspirated fluid for crystals in the diagnosis of gout.
PMID- 17041422
TI - Hypercapnic respiratory failure in systemic sclerosis.
AB - Respiratory failure from causes exclusive of intrinsic lung disease is rare in
systemic sclerosis. We report an unusual case of a young woman with diffuse
systemic sclerosis who presented with proximal muscle weakness, dyspnea, weight
loss, and nasal regurgitation. On physical examination, she had normal breath
sounds but severe limitation of chest wall expansion. Pulmonary function tests
(PFTs) were consistent with restrictive lung disease. Pulmonary pressures were
normal on right heart catheterization and chest radiography and high-resolution
computed tomography showed no evidence of intrinsic lung disease. Quadriceps
muscle biopsy was consistent with type II atrophy, without any element of
inflammatory myositis. After a meal, the patient aspirated, developed severe
persistent hypercapnia, and required ventilatory support. Therapy with
corticosteroids and intravenous gamma globulin failed to improve her condition,
and the patient subsequently expired. Hypercapnic respiratory failure on the
basis of chest wall involvement from systemic sclerosis may occur in the absence
of intrinsic lung disease, and the prognosis, as in this case, may be grave.
PMID- 17041423
TI - Systemic nocardiosis in a splenectomized patient with systemic lupus
erythematosus: successful treatment using linezolid.
AB - A splenectomized patient with systemic lupus erythematosus, who had previously
been treated with high doses of corticosteroids, presented with headaches and
symptoms of a respiratory tract infection. A magnetic resonance imaging scan of
the brain revealed a ring-enhancing lesion, and Nocardia asteroides was isolated
from a stereotactic biopsy specimen. After adverse reactions to a number of
antibiotics, infection control was finally achieved by the new oxazolidinone
drug, linezolid. Nocardiosis should be considered as a differential diagnosis in
all immunocompromised patients who develop an obscure infection; delay in
diagnosis and subsequent initiation of appropriate treatment often results in a
fatal outcome. Linezolid is a new option for the treatment of nocardiosis and is
effective when given orally.
PMID- 17041424
TI - Fasciitis in amyopathic dermatomyositis.
AB - Dermatomyositis is a disease frequently treated by rheumatologists and
dermatologists due to prominent systemic features of inflammatory myositis, less
common arthritis, and rare systemic vasculitis, in addition to the characteristic
cutaneous manifestations of Gottron's papules over extensor surfaces, and a
heliotrope rash over the eyelids. Patients with amyopathic dermatomyositis, a
subset of dermatomyositis, display skin disease but no apparent muscle disease.
This report describes an adult patient with the typical dermatomyositis rash with
no weakness, normal muscle enzymes, and the unique finding of fasciitis without
myositis on muscle biopsy, which correlated with a Magnetic Resonance Imaging
(MRI) finding of a peripheral halo of intense signal around muscles on T2
weighted and fat suppression sequences. Although MRI finding of presumed
fasciitis has been reported in juvenile-onset dermatomyositis, this is the first
report of MRI evidence of fasciitis with pathological correlation in adult-onset
dermatomyositis. We suggest that if MRI scans are ordered, as part of the work-up
of dermatomyositis, a peripheral halo of increased signal should specifically be
looked for, which could be interpreted as fasciitis based on this case report.
PMID- 17041425
TI - Iliac bone sarcoma presenting as hip pain.
PMID- 17041427
TI - Does the joint fluid help?
PMID- 17041426
TI - Molecular biology and immunology for clinicians 22: natural killer cell receptors
and activation mechanisms.
AB - Natural killer (NK) cells (called "third population cells" many years ago because
they did not bear surface markers of the first two defined populations, B cells
and T cells) are now known to occupy a pivotal position in the immune system,
straddling the "divide" between the innate and adaptive responses. Natural killer
cells are capable of production of many cytokines, both pro- and anti
inflammatory, and induction of target cell death by lysis and/or programmed cell
death (apoptosis). Some of these cytokines are pivotal in the autoimmune and
antipathogenic immune responses, implicating NK cells in the pathogenesis of many
human diseases. Multiple detection systems allow tight control of the potent
effector systems that mediate NK cells' effects. Recent studies have shown that
NK cell function is under tight control, with complex inhibitory and activating
signaling assuring that these cells can accurately detect intracellular infection
and malignant degeneration without damaging healthy cells. Although NK cell
receptors do not have antigenic specificity, they do detect certain patterns on
the surface of target cells. Their ability to make many cytokines that alter
antigen-specific immune responses mediated by other cells puts NK cells in a
unique position to influence both innate and adaptive responses.
PMID- 17041428
TI - Patient satisfaction with COX-2 guidelines at a Veterans Administration hospital.
PMID- 17041429
TI - Klinefelter syndrome with antisynthetase syndrome: why might they be associated?
PMID- 17041430
TI - Cyclic post methotrexate dosing arthritis in systemic lupus erythematosus.
PMID- 17041431
TI - Homocysteine and Behcet disease.
PMID- 17041432
TI - Regional musculoskeletal examination: what the students say.
AB - Confusion exists over which musculoskeletal examination skills medical students
should learn. This study aimed to explore the views of third-year medical
students. This was a qualitative study to allow in-depth exploration of beliefs
and attitudes. Twenty students were randomly assigned to 1 of 2 focus groups.
Their attitudes towards musculoskeletal examination were explored and discussed.
The groups' discussions were recorded, transcribed, and framework analysis was
undertaken with the aid of NUD*IST computer software. The following themes were
identified: students dislike eponymous names for clinical tests; students felt
there is a need for a more structured approach to musculoskeletal examination;
students appeared unaware that many clinical tests were not based on evidence;
students complained of a lack of confidence in the use of musculoskeletal
clinical tests. Student's confidence in their musculoskeletal examination skills
may be improved by the development of an agreed set of so-called core examination
skills.
PMID- 17041433
TI - Lupus pernio in sarcoidosis: clinical features and treatment outcomes of 14
patients.
AB - Lupus pernio (LP) is the most characteristic skin lesion of sarcoidosis. In this
study, we retrospectively evaluated the clinical features of sarcoidosis patients
with diagnosed LP at our center. Of 516 sarcoidosis patients diagnosed within a
36-year period, 14 (2.7%) had skin lesions that were clinically and
histologically diagnosed as LP. Thirteen of our LP patients were females, and one
was a male (mean age: 46.3, range: 24-67). In 2 sarcoidosis patients, the initial
presentation of the disease was LP. When the LP patients were compared with other
sarcoidosis patients, there were more females, and the frequency of
extrapulmonary involvement and the number of patients with advanced stage disease
were higher (P <0.001). Oral and/or intralesional steroid therapy was the
preferred treatment modality in all our patients and led to either recovery or
regression in most patients with LP. As our study was an uncontrolled,
retrospective one with few patients, it is difficult to say whether steroids are
effective. LP runs a chronic course and spontaneous remission of lesions of more
than 2 years' duration is quite rare. Because of the unwanted side effects of
steroids, the efficacy of new treatment modalities should be tested especially in
sarcoidosis patients with only skin involvement.
PMID- 17041434
TI - Evidence for disseminated Mycoplasma fermentans in New Jersey residents with
antecedent tick attachment and subsequent musculoskeletal symptoms.
AB - Mycoplasma species are one of nature's most abundant groups of microbes. These
bacteria inhabit a wide diversity of insect, plant, and animal species, including
humans. Certain mycoplasma species have been identified in blood-sucking
arthropods, including Ixodes ticks. Frequent human exposure to this genus of
ticks led us to explore the possibility of tick-mediated transmission of these
bacteria. We evaluated 7 residents of central New Jersey who developed fatigue,
musculoskeletal symptoms, and cognitive disturbance after tick attachment. All 7
of these patients lacked both serological evidence and erythema migrans skin
lesions characteristic of Lyme disease. We were able to amplify and quantitate
Mycoplasma fermentans-specific DNA from their peripheral blood lymphocytes. After
antimicrobial therapy, symptoms subsided, and M. fermentans DNA could no longer
be detected in their blood specimens. These findings suggest that a subset of
disseminated M. fermentans infections may be a vector-mediated process in humans
and should be considered in patients with puzzling musculoskeletal presentations.
PMID- 17041435
TI - Historical vignette: Raynaud's phenomenon as perceived by musculoskeletal
specialists (1862-1957).
PMID- 17041436
TI - Transient renal dysfunction with Raynaud's phenomenon: is there a connection?
AB - We describe a patient with an episode of severe Raynaud's phenomenon and early or
mild scleroderma who presented with a transient elevation of her serum creatinine
that resolved spontaneously after 2 days. Vascular response to cold temperatures
has been described in vascular beds other than the extremities, and a similar
phenomenon in the kidney might have been responsible for the transient renal
dysfunction. Possible mechanisms to explain this phenomenon are discussed.
Vasospasm merits consideration as an uncommon but largely reversible cause of
elevated creatinine in patients with Raynaud's phenomenon.
PMID- 17041437
TI - Relapsing polychondritis with involvement of posterior inferior cerebellar artery
causing acute lateral medullary syndrome.
AB - We present a patient with relapsing polychondritis who presented with findings of
lateral medullary syndrome, known as the syndrome of Wallenberg, produced by
infarction of a wedge of lateral medulla lying posterior to the inferior olivary
nucleus. Angiographic examination showed complete occlusion of the right
posterior inferior cerebellar artery and segmental narrowings in the basilar
artery. We believe that the angiographic findings were based on an underlying
vasculitis because of his relapsing polychondritis. This is the first case of
relapsing polychondritis with angiographically demonstrated posterior inferior
cerebellar artery involvement. Although this syndrome is usually a result of
atherosclerosis, our case suggests that vasculitis must also be considered
because it may respond to treatment with corticosteroids.
PMID- 17041438
TI - Successful treatment with low-dose thalidomide in a patient with both Behcet's
disease and complex regional pain syndrome type I: case report.
AB - Thalidomide is a recognized treatment of Behcet's disease. Low-dose thalidomide
seems to be effective in the treatment of orogenital ulcers and is potentially
safer with a lower incidence of adverse effects than higher doses. We wish to
report a case of Behcet's disease in a 33-year-old woman who responded well to
thalidomide 50 mg 2 to 4 times per week. Her disease manifestations (severe
orogenital ulceration, pseudofolliculitis, mild thrombophlebitis, positive
pathergy response, and fatigue) were previously resistant to courses of
prednisone, dapsone, colchicine, various types of mouthwash, and topical steroid
preparations. She also gave a history of complex regional pain syndrome type I
(CRPS 1) over her left patella (severe pain, intermittent edema, hyperalgesia,
allodynia, cold skin, and loss of movement) after a fall onto her left knee 6
years previously. This had only partially responded to a variety of treatment
modalities. After starting thalidomide for her Behcet's disease, the pain in her
left knee unexpectedly disappeared. There are rat experiments showing that
thalidomide improves neuropathic pain, probably by selectively blocking tumor
necrosis factor-alpha production in activated macrophages. We believe this is the
first report of successful use of thalidomide in a human being with CRPS 1, and
we therefore recommend that thalidomide should be considered in the treatment of
CRPS 1.
PMID- 17041439
TI - When thought leaders mislead: "discoid lupus is not related to SLE".
PMID- 17041440
TI - Differentiating the new rheumatoid arthritis biologic therapies.
AB - Current understanding of the mechanisms behind the pathogenesis of rheumatoid
arthritis (RA) has led to the development of therapies involving biologic agents
that target specific mediators of the disease process. Although the biologic
agents used to treat RA share the ability to alter the cytokine cascade, they
differ in ways that are clinically important. For example, they vary with regard
to how they block cytokine activity (ie, as receptors, as receptor blockers, or
as anticytokine antibodies) and the particular cytokine they target (eg, tumor
necrosis factor [TNF] versus interleukin-1). Biologic therapies for RA also
differ in mode of administration. Several are administered subcutaneously,
whereas others are given intravenously. They also have molecular dissimilarities
that result in differences in pharmacokinetics (ie, long versus medium half-life)
and that may influence their safety profiles.Some biologic agents, such as the
TNF inhibitors etanercept and infliximab, have been rigorously examined for long
term safety and efficacy, whereas other agents, like the TNF inhibitor
adalimumab, have not. Differences between the various biologic agents may relate
to the usefulness of each individual drug as a long-term treatment in RA. For
example, the need for physician visits may impact the practicality of drugs that
are administered intravenously. Also, physicians should be aware that use of
cytokine inhibitors increases the risk of infection. The prevalence of
tuberculosis during therapy with infliximab exceeds the background rate in
patients with RA. Accordingly, physicians should be familiar with the updated
warnings in the package inserts that accompany these drugs.
PMID- 17041441
TI - Examination of the risk of continuous leflunomide treatment on the incidence of
infectious complications after joint arthroplasty in patients with rheumatoid
arthritis.
AB - SYNOPSIS: To determine whether the risk of infectious complications after total
joint arthroplasty is increased in rheumatoid arthritis patients who are treated
continuously with leflunomide, the incidences of infectious complications in 41
rheumatoid arthritis patients who received continuous leflunomide treatment
(leflunomide group) and in 41 patients who did not receive leflunomide within 4
weeks of surgery (nonleflunomide group) were compared. The incidence (6.1%) of
local infection after surgery in the leflunomide group (82 procedures) was
slightly lower than that (6.3%) in the nonleflunomide group (79 procedures).
There were no systemic or deep infections. None of the other variables analyzed
were identified as risk factors for postoperative complications. The results
indicate that there is no dramatically increased risk of postoperative infectious
complications in rheumatoid arthritis patients who continue to be treated with
low doses of leflunomide perioperatively.
PMID- 17041444
TI - Acute inflammatory arthritis: an adverse effect of clopidogrel?
PMID- 17041442
TI - Molecular biology and immunology for clinicians 23: autoimmunity and the
superfamilies of tumor necrosis factor and tumor necrosis factor receptor.
AB - The parsimony of nature can be stated as "if its not broke don't fix it, just
tweak it and reuse it again and again." Nature recycles: once a motif is
demonstrably useful it shows up again, often in unexpected places. Tumor necrosis
factor and its receptor(s) are examples of this. At least 20 molecules have now
been identified as being 25% homologous or more identical with tumor necrosis
factor and being involved in a variety of immune and nonimmune functions. Members
of the receptor superfamily have shared structural motifs and trigger shared
intracellular signaling pathways. Rather than having been implicated in arcane
and rare syndromes, some of these activities are pivotal in immune function and,
when perturbed, some predispose to known immunodeficiency and autoimmune disease.
Not surprisingly, some of these are becoming targets for immunomodulation. New
members of these 2 superfamilies are currently being described and the newcomers
and the "original stock" will show up in the clinic before you know it! Part of
the confusion has always been that each laboratory describing a new biologic
principle names the mediating compound. Thus, multiple labs, multiple names for
the same protein (recall Ro/SS-A, La/SS-B). Thus, special attention is paid below
to acronyms and their synonyms.
PMID- 17041445
TI - Annular, semicircular lipoatrophy of the thighs associated with incomplete
"CREST" syndrome: Raynaud's, telangiectasias, and esophageal dysmotility.
PMID- 17041447
TI - Evaluating treatment efficacy: potential biases behind randomized controlled
trials.
PMID- 17041448
TI - Topical treatment of osteoarthritis of the knee with herbal products: promising
results but still questions.
PMID- 17041449
TI - The impact of disease activity on the quality of life, mental health status, and
family dysfunction in colombian patients with rheumatoid arthritis.
AB - This study investigated the relationship between activity of disease, mental
health status, quality of life, and family dysfunction in northwestern Colombian
patients with rheumatoid arthritis (RA). Seventy-nine patients completed a 2
phase study that included physical examination (objective measurement of disease
activity according to adapted American College of Rheumatology criteria) and a
pretested questionnaire that sought information on helplessness, disability,
depression, anxiety, quality of life, arthritis self-efficacy for pain, and other
symptoms, as well as family dysfunction and socioeconomic status. Nineteen
patients (24%) had active RA, 48 (61%) had moderately active RA, and 12 (15%)
were in remission. Symptoms of depression, helplessness, disability, pain,
anxiety, lower quality of life, and self-efficacy were associated with RA
activity regardless of age, sex, and duration of the disease. Symptoms of
depression were directly correlated with anxiety, helplessness, pain, and
disability and inversely correlated with quality of life and self-efficacy.
Although family dysfunction was present in 39% of patients, no associations
between family dysfunction, activity of RA, mental health variables,
socioeconomical status or quality of life were observed. These results indicate
that RA activity significantly influences mental health status and quality of
life in this population. Accordingly, a holistic conception of therapy should
guide the treatment of patients with RA.
PMID- 17041450
TI - The decreasing prevalence of uveitis associated with juvenile rheumatoid
arthritis: do NSAIDs play a role?
AB - We studied the prevalence and characteristics of chronic uveitis in a population
of children diagnosed with juvenile rheumatoid arthritis (JRA). Uveitis is one of
the most important, potentially debilitating extra-articular manifestations of
JRA and has been observed in as many as 20% of cases. The medical records of 230
patients diagnosed with JRA and treated at a tertiary care hospital ophthalmology
clinic between 1992 and 2000 were retrospectively reviewed. Seventeen patients
(7.4%) were found to have clinical features of uveitis. There was a preponderance
of female patients (16/17) and pauciarticular disease (13/17). Only 12 of 17 were
ANA positive. Six had uveitis at diagnosis. Patients who were receiving naproxen
had less incidence of uveitis compared with those receiving other nonsteroidal
antiinflammatory drugs. Despite a relatively low prevalence of uveitis,
complications occurred in about 24% (4/17) of the patients, even with adequate
treatment and close monitoring. The prevalence of uveitis in JRA seems to be
decreasing and may be secondary to the increased use of naproxen. However,
routine ophthalmologic screening should be continued in patients with JRA to
avoid potential complications of chronic uveitis.
PMID- 17041451
TI - Hypertension and elevated ESR as diagnostic features of Takayasu arteritis in
children.
AB - Takayasu arteritis (TA) is an inflammatory disease of the aorta and its branches.
Delay in diagnosis is a common problem for adults and children. Although early
manifestations are nonspecific (i.e., malaise, fever, anorexia, weight loss,
myalgia, arthralgia/arthritis, elevated acute phase reactants), the clinical
features that lead to diagnosis often appear suddenly and are related to vascular
involvement. Hypertension, which is rare in children, and elevated ESR are found
in most patients with TA. The authors hypothesized that these features, then,
could be used as way to raise the clinical suspicion of TA. A total of 190 young
patients with TA were retrospectively analyzed from local records and the
literature to find the signs and symptoms associated with the disease that could
be used to educate caregivers about when to suspect TA and to provide a screening
tool for the disease. Hypertension and elevated ESR are found in most patients
with TA. For this local study group, the sensitivity of this combination was 67%.
Including the literature sources for which patient-specific information was
available, the overall sensitivity was 65%. Thus, the combination of hypertension
and elevated ESR in pediatric patients should merit further screening for TA,
particularly in those with systemic complaints. Physical examination should focus
on pulse abnormalities. Further evaluation should involve extensive imaging of
the vascular system.
PMID- 17041452
TI - Effect of a topical herbal cream on the pain and stiffness of osteoarthritis: a
randomized double-blind, placebo-controlled clinical trial.
AB - This study compared the efficacy of an herbal ointment to a placebo ointment in
relieving the pain and stiffness of osteoarthritis. The herbal preparation
contained substances believed by alternative practitioners to be helpful in
treating osteoarthritis. This study was a double-blind randomized placebo
controlled clinical trial. Subjects were solicited from patients attending an
arthritis clinic in Dallas, Texas. Selection of subjects with osteoarthritis was
based on the criteria developed by the American College of Rheumatology. Subjects
were randomized to an active (n = 11) or a placebo (n = 8) group. Herbal ointment
and control contained small amounts of capsaicin and menthol and were similar
when applied. Subjects graded their levels of pain and stiffness for a 1-week no
treatment baseline. Subjects then applied the herbal or sham ointment to the
involved joint(s) for 28 consecutive days and recorded their levels of pain and
stiffness daily on visual analog scales. Significant differences between the
active and placebo groups for pain (P < 0.05) and stiffness (P < 0.05) were found
when the baseline phase was compared with the fourth week. An herbal ointment was
shown to be effective in relieving the pain and stiffness of osteoarthritis
without adverse effects. If future studies confirm effectiveness of this
treatment, it may have a role as an adjunct to standard drug therapy.
PMID- 17041453
TI - Incidence of nonvertebral fractures in relation to time on treatment and bone
density in glucocorticoid-treated patients: a retrospective approach.
AB - The effects of duration of treatment and bone mineral density (BMD) on
nonvertebral fracture in 560 glucocorticoid users were examined by using baseline
and retrospective data from 2 parallel studies assessing the efficacy and safety
of alendronate therapy. Baseline spine and hip BMD were significantly (P < 0.01)
lower with increased time spent receiving glucocorticoids. Forty-three patients
(7.7%) had experienced at least 1 nonvertebral fracture after starting
glucocorticoid treatment. The hazard function for nonvertebral fracture
occurrence increased significantly (P < 0.01) with time spent receiving
glucocorticoids: fracture incidence per 1,000 person-years on glucocorticoids was
18 (< 5 years), 31 (5-10 years), and 35 (> 10 years). Patients with a history of
nonvertebral fractures after starting glucocorticoid treatment had significantly
lower lumbar spine (P < 0.01) and hip (< 0.01) BMD value than those without
fractures. This retrospective analysis suggests that a BMD measurement of spine
and hip may identify risk for nonvertebral fractures in a heterogeneous
population of glucocorticoid users.
PMID- 17041454
TI - Reactivation of systemic lupus erythematosus after initiation of highly active
antiretroviral therapy for acquired immunodeficiency syndrome.
AB - As the demographics of human immunodeficiency virus (HIV) infection continue to
include more African-American and Hispanic females, the prevalence of concomitant
HIV infection and systemic lupus erythematosus (SLE) may increase. We describe a
36-year-old woman with a 19-year history of active SLE who, after acquiring HIV
infection, developed quiescent SLE with advanced immunosuppression (CD4 cell
count 10/2%). After presenting with an opportunistic infection, she began
receiving highly active antiretroviral therapy. Throughout a 6-month period,
highly active antiretroviral therapy resulted in suppression of her viremia, as
well as a concomitant rise in her CD4 cell count. With recovery of her immune
status, she presented with transverse myelitis caused by her SLE, which responded
well to intravenous steroids. There have been several observations of quiescence
of lupus disease activity with advanced immunosuppression in HIV patients. This
is a report of the recurrence of rheumatic disease in an acquired
immunodeficiency syndrome patient after the initiation of highly active
antiretroviral therapy. We recommend careful observation of HIV patients for
reactivation of rheumatic disease while initiating highly active antiretroviral
therapy.
PMID- 17041455
TI - Subcutaneous nodules and joint deformity in leprosy: case report and review.
AB - Leprosy (Hansen's disease), known to be caused by Mycobacterium leprae, is a well
known illness with multiple rheumatologic manifestations. This chronic
granulomatous infection has clinical features that are variable, depending on the
immune response of the host. Manifestations consist mainly of involvement of the
peripheral nerves, skin, upper respiratory system, eyes, and testes, as well as
joints. Musculoskeletal manifestations include arthralgias, arthritis, Charcot
arthropathy, and positive autoantibodies. We report a case of a Puerto Rican-born
woman who was living within the northeastern United States and had subcutaneous
nodules, saddle nose deformity, and painless contractures of her fingers and
toes. This case illustrates some of the musculoskeletal manifestations of leprosy
to raise awareness of this disease as part of the differential diagnosis of
articular abnormalities with subcutaneous nodules in a nonendemic country.
PMID- 17041456
TI - Underuse of intra-articular and periarticular corticosteroid injections by
primary care physicians: discomfort with the technique.
AB - Musculoskeletal disorders account for 11% to 13% of office visits in ambulatory
care clinics and 9% of all physician visits in the United States. Intra-articular
or periarticular aspiration or injections are an integral part of the management
of arthritis or periarthritis. Our aim was to determine the use and level of
comfort of administering intra-articular and periarticular injections by primary
care physicians (PCPs) practicing in a university setting.A self-administered
questionnaire with 20 questions querying experience and training in local
injection therapy was mailed to 82 physicians (junior residents, senior
residents, and faculty) offering primary care at the University of Chicago.
Comfort scores were measured with a scale of 1 to 10 (1 = minimum and 10 =
maximum). The response rate to the questionnaire was 67% (36 residents and 19
faculty). Seventy-one percent of PCPs routinely suggested the procedure for
severe arthritis and bursitis, but only 19% had (self-administered) performed it
themselves. Eighty-nine percent of the PCPs referred their patients to specialty
clinics. Forty-eight percent referred their patients to rheumatology, 11.5% to
orthopedics, and 29% to both. Other PCPs were consulted for the procedure by
9.6%. Discomfort with the performance of the technique was the predominant reason
for 83% of the referrals. The mean comfort score for intra-articular or
periarticular injections was 3.10 +/- 2.14 in general and 4.45 +/- 2.92 for knee
joint. The mean comfort score for other joints and bursae ranged from 1.20 to
2.15. Ninety-five percent of PCPs regarded themselves to be inadequately trained.
Regarding the training, 41% had received a lecture during medical school and
residency, while 40% had received demonstration of the techniques during
residency. Of the faculty, 26% had never received any formal lecture, and 5.2%
had never received formal demonstration of the techniques during their training.
Joint injections observed ranged from 89% for knee to 59% for shoulder and 22%
for wrist joints. Only 11% of faculty had performed more than 5 intra-articular
injections during their training. A need for formal training in these techniques
was identified by 95% of the subjects, of whom 65% thought the residency period
was the best time to do so. Performing 5 to 10 intra-articular injections during
residency was considered optimal training by 60%. On subanalysis, the mean
comfort scores were higher in the residents in general (3.60 +/- 2.29 versus 2.18
+/- 1.47;P = 0.01) as compared with faculty. The residents' scores were also
higher across different joints as compared with those of faculty but assumed
statistical significance only for olecranon bursa injection (2.32 +/- 2.76 versus
1.27 +/- 0.67;P = 0.04) and subacromial bursa injection (2.08 +/- 2.27 versus
1.27+/- 0.75;P = 0.06). The mean comfort scores were lower by 1.74 (P = 0.007)
for women physicians. There is underuse of self-administered intra-articular and
periarticular injection techniques by PCPs in the management of arthritis or
periarthritis. The reasons include inadequate training and low comfort in
performing these procedures. Eighty-nine percent of PCPs would refer their
patients to subspecialty clinics for these "routine" injections. There is a clear
need for a training in these procedures during residency.
PMID- 17041457
TI - Evidence-based soft tissue rheumatology. Part I: subacromial impingement
syndrome.
AB - Impingement into the coracoacromiohumeral space, a common cause of rotator cuff
tendinopathy, may result from an impinging osteoligamentous upper boundary,
abnormalities in the tendon itself, or failure of muscles that retain the humeral
head on the glenoid. An overuse mechanism is clearly a risk factor in throwing
athletes, whereas occupational overuse may contribute to its development in
nonathletes. The subacromial anesthetic injection test remains as the
acknowledged gold standard for diagnosis. There is evidence on the therapeutic
efficacy of nonsteroidal antiinflammatory drugs, glucocorticoid subacromial
injection, and acupuncture as compared with placebo. Also, acromioplasty appears
to be better than physiotherapy. Patients with rotator cuff tendinopathy may be
successfully treated with nonsteroidal antiinflammatory drugs, a glucocorticoid
subacromial injection, or acupuncture. In failures of conservative therapy,
surgery should be considered. Further research is required on etiology,
diagnosis, natural course, and validity of many treatments currently used in this
common condition.
PMID- 17041458
TI - Molecular biology and immunology for clinicians 24: phylogeny of the immune
system.
AB - The human immune system consists of layer upon layer of response, communication,
and coordination mechanisms added during its evolution throughout the last half
billion years. Given the parsimony of nature, it is not surprising that many of
the systems prominent within the human immune response are recognizable within
the immune systems of less advanced species. Insights drawn from these species
and common sense suggest that "autoimmune" reactivity was not the original or
primary reason for the evolution of these mechanisms. Also, it becomes clear that
certain functions thought to be "immune" may actually be nonspecific, really
innate functions served by these ancient mechanisms. There is good evidence of
communication between levels of the immune system, the innate and adaptive
systems working with each other, often the former (not antigen-specific)
preceding and serving to trigger or magnify the latter (antigen-specific). A
future article in this series will focus more on the innate system and how it
interdigitates with the adaptive system.
PMID- 17041459
TI - Pseudogout and gout in a patient after liver transplantation for primary biliary
cirrhosis: what might be the association?
PMID- 17041460
TI - Use of a dopamine against in fibromyalgia: where is the evidence?
PMID- 17041461
TI - Influence of leflunomide on renal handling of urate and phosphate in patients
with rheumatoid arthritis.
AB - Reduction of serum urate and phosphate levels has been observed in patients
receiving leflunomide therapy, but the mechanism for such changes has not been
evaluated. Thirty-eight patients with rheumatoid arthritis who began leflunomide
were studied. Serum urate, creatinine, and phosphate, and 24-hour uric acid,
creatinine, and phosphate were measured before, during, and in some instances
after leflunomide treatment. Clearances of urate and creatinine, fractional
excretion of urate, and tubular reabsorption of phosphate were calculated.
Undissociated urinary uric acid was estimated with a nomogram. Twelve patients
gave consent to withdraw leflunomide treatment of a 2-week period and underwent a
third study. Decreases in serum urate and phosphate levels were observed, with
parallel increases in clearances of urate and in fractional excretion of urate,
and a reduction in tubular reabsorption of phosphate. Clearances of creatinine
and undissociated urinary uric acid remained unchanged. Two weeks after
withdrawing the drug, a partial return toward baseline values was observed, but
residual changes were apparent. No case of clinical gout was observed.
Leflunomide enhances urate and phosphate loss, an effect that partially persisted
after 2-week withdrawal. The long-term effect of mild phosphate wasting warrants
further investigation. The urate-lowering effect of leflunomide may be useful in
monitoring compliance in leflunomide therapy.
PMID- 17041462
TI - Abnormalities of bone mineral density and bone metabolism in Venezuelan patients
with rheumatoid arthritis.
AB - Patients with rheumatoid arthritis (RA) are at increased risk for osteoporosis
and bone fractures. To our knowledge, the frequency of osteopenia and
osteoporosis in patients with RA from Latin America has not been established. In
this study, we have examined the bone mineral density (BMD) by dual-energy x-ray
absorptiometry, as well as biochemical markers of bone metabolism, in a
population of 85 Venezuelan RA patients. Twenty-seven patients (29.4%) fulfilled
the World Health Organization's (WHO) criteria for either trabecular osteopenia
or osteoporosis compared with 10 healthy controls (8.1%; odds ratio [OR] = 3.25;
P = 0.004). In addition, 30 patients (26.4%) showed cortical osteopenia or
osteoporosis compared with 5 healthy controls (4.0%; OR = 8.18; P < 0.00001).
Past or concurrent use of prednisone or methotrexate was not related to decreased
BMD. Rheumatoid patients showed increased serum levels of osteocalcin (P = 0.002)
and 24-hour urine excretion of N-telopeptide cross-links (P = 0.03). The bone
marker profiles suggest an increased bone turnover during the premenopausal stage
in these patients. After menopause, a resorptive pattern seems to predominate,
leading to accelerated bone mass loss in RA patients. In conclusion, Venezuelan
female patients with RA may be at increased risk for osteopenia or osteoporosis,
particularly after menopause. Our study supports the initiation of antiresorptive
medication in Latin American premenopausal patients with RA, as in other ethnic
groups, to diminish the risk of osteoporosis in the postmenopausal stage.
PMID- 17041463
TI - A look at rheumatology in China (2002).
AB - This report describes a visit by an international group interested in
Rheumatology to the Rheumatology centers and traditional Chinese medicine units
in the People's Republic of China. Differing disease patterns and treatment
approaches offer opportunities for studies and collaborations. We can also learn
from the traditional Chinese approach with individualization of therapy and
attention to health maintenance.
PMID- 17041464
TI - Bronchiolitis obliterans with organizing pneumonia associated with scleroderma
and scleroderma spectrum diseases.
AB - Systemic sclerosis (SSc) is an autoimmune disorder with a high mortality rate
from pulmonary manifestations, such as interstitial lung disease and pulmonary
hypertension, seen at autopsy in 90% and 75% of patients, respectively.
Bronchiolitis obliterans with organizing pneumonia (BOOP) has numerous causes,
but it has only been reported in three patients with SSc. We present three cases
of biopsy-proven BOOP in patients with scleroderma spectrum disease, including
diffuse cutaneous SSc, mixed connective tissue disease with SSc features, and
limited cutaneous SSc that later evolved to dermatomyositis/SSc overlap. BOOP and
SSc alveolitis have similar findings on spirometry, radiographs, and BAL; the
definitive diagnosis of BOOP was therefore made by open lung biopsy.
Cyclophosphamide is the current treatment of alveolitis associated with SSc,
whereas high-dose prednisone is used to treat BOOP. As a result of this
difference, we emphasize the importance of a thorough investigation of pulmonary
disease in SSc patients to exclude BOOP and treat appropriately.
PMID- 17041465
TI - Cavitary necrobiotic nodule imitating malignant lung disease in a patient without
articular manifestations of rheumatoid arthritis.
AB - Pulmonary involvement is a serious complication of rheumatoid arthritis (RA) and
may be seen as airway disease, rheumatoid nodules, interstitial lung disease, and
pleurisy. However, cavitary rheumatoid nodules without articular manifestations
are rare. We describe a male patient presenting with pleurisy and multiple
rheumatoid necrobiotic nodules in the absence of arthritis or subcutaneous
nodules. One of the nodules was quite large (5 x 8 cm in diameter) and cavitary,
imitating bronchial carcinoma radiologically and bronchoscopically. Definite
histopathologic diagnosis was obtained by open lung biopsy. The patient was given
methylprednisolone and methotrexate, and significant regression was observed in
clinical and radiologic findings. He has been followed for 14 months with no
articular manifestations yet, receiving 4 mg/d methylprednisolone and 20 mg/wk
methotrexate. The diagnosis of rheumatoid pulmonary involvement without articular
manifestations can be difficult. Rheumatoid nodules may imitate bronchial
carcinoma, or bronchial carcinoma may coexist in RA patients. Open lung biopsy
may be necessary for differential diagnosis of pulmonary lesions in RA.
PMID- 17041466
TI - Macrophage activation syndrome in a patient with systemic onset rheumatoid
arthritis: rescue with intravenous immunoglobulin therapy.
AB - We report the case of a 7-year-old boy with systemic onset juvenile rheumatoid
arthritis (JRA) who developed macrophage activation syndrome during a period of
relative remission. He presented with high-grade fever, enlarged lymph nodes,
acute hepatitis, severe pancytopenia, and evidence of disseminated intravascular
coagulopathy. He became severely ill, with persistent mucosal bleeding,
hypovolemia, and vascular instability, and he was admitted to the intensive care
unit. No response was observed to treatment with high-dose intravenous
corticosteroids and blood product replacements, but the patient fully recovered
after the completion of two pulses of intravenous immunoglobulin. This treatment
modality may be an alternative to anti-TNF-alpha and cyclosporine A for a prompt
response in JRA patients with this potentially fatal condition.
PMID- 17041467
TI - Panniculitis: a presenting manifestation of disseminated histoplasmosis in a
patient with rheumatoid arthritis.
AB - We report a case of histoplasma panniculitis in a patient with rheumatoid
arthritis treated with multiple immunosuppressive agents including infliximab.
The patient presented with erythematous plaques involving the right upper
anterior abdominal wall, the right flank and later extension to involve the left
flank and the left axilla. The histopathologic examination of these lesions was
consistent with lobular panniculitis and the cultures of these lesions and blood
grew Histoplasma capsulatum. The clinical and histopathologic picture of
histoplasma panniculitis and rheumatoid arthritis-associated panniculitis can be
very similar, but the treatment is clearly different. Our case emphasizes the
importance of considering rare manifestations of opportunistic infections in an
era of widespread use of immunosuppressive medications in the field of
rheumatology.
PMID- 17041468
TI - Refractory pulmonary hypertension in a lupus patient with occult pulmonary
vasculitis.
AB - Primary pulmonary hypertension is a disease that has become increasingly
recognized in lupus patients. Pathologic findings from lupus patients usually do
not differ from those who have idiopathic pulmonary hypertension. In recent
years, intravenous vasodilator therapy has improved morbidity and mortality in
patients with primary pulmonary hypertension. In this case report, we describe a
young woman with severe pulmonary hypertension refractory to aggressive
parenteral vasodilator treatment. Steroid treatment was initiated after a
tentative diagnosis of lupus was made on the basis of the presence of Raynaud's
phenomenon, proteinuria, pericarditis with tamponade, and a positive anti-Ro
antibody. Despite treatment with vasodilators and steroids, the patient's
condition rapidly deteriorated and she died. Unexpectedly, active pulmonary
arteritis was demonstrated at autopsy. This case suggests that immunosuppressive
therapy should be considered in lupus patients with severe pulmonary hypertension
who are refractory to aggressive vasodilator therapy and high-dose parenteral
steroids.
PMID- 17041471
TI - Crohn disease worsened by anakinra administration.
PMID- 17041469
TI - Molecular biology and immunology for clinicians 25: defense collagens.
AB - The adaptive immune response specializes in reacting efficiently and rapidly with
protein antigens. Many pathogens and host cells are coated with carbohydrates
(more about lipid antigens and the response thereto in a future installment of
this series). The carbohydrate arrays on pathogens are remarkable for their
relative lack of diversity, remarkable conservation, and how different they are
from the carbohydrates found on mammalian cells. Thus, they represent excellent
targets for the innate immune response, which is characterized by limited
effector molecule heterogeneity. Defense collagens are a class of innate immune
response recognition proteins targeting these common carbohydrate motifs, a class
you may not have encountered previously. These invariant germ-line encoded
proteins are not produced as a specific response to a particular antigen.
Nonetheless, they too have an antigen-binding site, called the carbohydrate
recognition domain with the other end of the molecule (made up of collagen-like
domains) devoted to the transmission of biologically relevant information,
analogous with the antibody molecule's Fc component, but this is where the
similarities end. Defense collagens have been broadly viewed as an "anti
antibody," broadly similar in structure and function. Despite the fact that they
are germline-encoded and do not have individual antigen specificity, their
phylogenetic longevity and durability prove the value of defense collagens in
maintaining the host. On the basis of emerging studies, they may play important
roles in the defense against many pathogens and in the pathogenesis of
rheumatologic and other diseases. Thus, they are good targets for studies to
better understand our diseases and to craft therapeutic manipulations in the
future.
PMID- 17041472
TI - Ropinirole, open preliminary observations of a dopamine agonist for refractory
fibromyalgia.
PMID- 17041473
TI - Comment on Furst's editorial: postmarketing surveys: up sides and down sides.
PMID- 17041475
TI - Possible relationship between AA amyloidosis and decreased complements in
patients with rheumatoid arthritis.
PMID- 17041476
TI - Modafinil for the treatment of fatigue of fibromyalgia.
PMID- 17041477
TI - Rheumatoid nodulosis: a diagnostic dilemma.
PMID- 17041478
TI - Are isolated antinucleolar antibodies a marker of scleroderma?
AB - This study was designed to determine the prevalence and positive predictive value
of isolated antinucleolar antibody (ANA) in scleroderma patients. We identified
73 rheumatology clinic patients with isolated ANAs. ANA titers greater than 1:160
were considered positive. The overall prevalence of isolated ANAs was 2.9%. The
prevalence of isolated ANAs in scleroderma, systemic lupus erythematosus (SLE),
and rheumatoid arthritis were 20.3%, 2.68%, and 3.3%, respectively. Scleroderma
and SLE were present in 12 patients (16.4%) each. Other rheumatologic disorders
identified in these patients were RA (12.3%), undifferentiated connective tissue
disease (8.2%), mixed connective tissue disease (4.1%), vasculitis (6.8%),
fibromyalgia (8.2%), osteoarthritis (5.4%), crystal-related arthropathy (6.8%),
seronegative arthritis (2.7%), sarcoidosis (4.1%), and others (8.2%). There were
no statistically significant differences in the median ANA titers in scleroderma
versus systemic lupus (P = 0.16) or undifferentiated connective tissue disease (P
= 0.18). The median titers were higher in scleroderma in comparison with
rheumatoid arthritis (P = 0.01), osteoarthritis (P = 0.007), fibromyalgia (P =
0.001), and crystal-related arthropathy (P = 0.009). Isolated ANAs have poor
sensitivity (20.3%) and the positive predictive value for this test is only 16.4%
for scleroderma.
PMID- 17041479
TI - Rheumatoid nodulosis: is it a different subset of rheumatoid arthritis?
AB - Rheumatoid nodulosis is an entity that describes a particular variant of
polyarthritis associated with early manifestations of palindromic rheumatism,
radiologic subchondral bone cysts, and subcutaneous rheumatoid nodules. This
study describes the clinical, radiologic, histologic, crystallographic, and
laboratory findings, as well as the outcome in a group of 16 patients with
rheumatoid nodulosis that were followed for a period of 1-12 years. Six of these
patients had an aggressive course and developed classic erosive polyarticular
rheumatoid arthritis, while the others continued having episodic arthritis
without erosive disease. Seven patients had cholesterol crystals in olecranon
bursae containing nodules. Second-line drugs used to control the articular
manifestations did not improve the nodulosis, erosive, or cystic subchondral bone
changes. Rheumatoid nodulosis mimics several other rheumatic diseases, and in
about 40%, classic erosive rheumatoid arthritis develops. The presence of
cholesterol crystals in rheumatoid nodules or affected bursae can increase the
confusion with other crystal-induced arthritis, in particular, tophaceous
monosodium urate gout or xanthomatosis.
PMID- 17041480
TI - Persistent hiccups associated with intravenous corticosteroid therapy.
AB - Singulata, commonly known as hiccups, have many causes and are most often
idiopathic and short-lived. Occasionally, hiccups can be persistent and becoming
quite bothersome, distracting, and even disabling. Many medications have been
implicated as a cause of hiccups. Although uncommon, corticosteroids and
benzodiazepines are 2 classes of drugs most frequently associated with the
development of hiccups. The following case series describes 5 patients with
intravenous corticosteroid-associated hiccups reported to our adverse drug
reaction reporting system between January 1998 and December 2000. Physicians
using intravenous corticosteroids should be aware of this potential complication.
PMID- 17041481
TI - The use of topical tacrolimus (FK506/Protopic) in cutaneous manifestations of
autoimmune diseases.
AB - The cutaneous manifestations of autoimmune diseases, including systemic lupus
erythematosus, are common and often recalcitrant to treatment. Unfortunately,
therapy for lupus and other autoimmune skin diseases has not advanced and relies
heavily on the use of oral and topical corticosteroids. Frequently, treatments
prove less than ideal, either from toxicity or lack of efficacy. A topical form
of the immunomodulating transplant medication, tacrolimus (FK-506, Protopic), has
recently been developed and approved for use in treating atopic dermatitis. Its
mechanism of action and local route of administration render tacrolimus a
potentially attractive novel therapeutic alternative for the treatment of various
autoimmune dermatologic conditions. We report our successful experience using
this drug in 3 patients with autoimmune dermatologic disease who were referred to
a tertiary care subspecialty clinic.
PMID- 17041482
TI - Valvular disease and myocardial infarctions in a patient with Behcet disease.
AB - Cardiac involvement occurs in less than 5% of Behcet patients, and coincidence of
regurgitation of the aortic and mitral valves and myocardial infarctions is rare.
This report describes a 49-year-old Turkish man with Behcet disease (BD) of 6
years' duration who presented with reduced left ventricular function. Both aortic
and mitral valves had to be replaced. Five months later, the patient presented
with non-ST segment elevation myocardial infarction. Only 1 month later, the
patient was successfully resuscitated after an acute ST segment elevation
inferior myocardial infarction. Coronary arteries were normal in appearance at
angiography before valvular replacement and at autopsy 2 years later. This report
should increase awareness of cardiac involvement in BD and its potential danger.
Even in BD patients without atherothrombotic plaques, myocardial infarctions can
happen. Early and adequate immunosuppressive treatment might have reduced cardiac
morbidity in this patient.
PMID- 17041483
TI - The management of chronic noninfectious synovitis ca. 1818.
PMID- 17041484
TI - A case of isolated sacral and pelvic sarcoidosis diagnosed by bone marrow biopsy.
AB - Although sarcoidosis frequently involves bone, it rarely presents as isolated
osseous disease. We present a case in which sarcoidosis is limited to the sacrum
and pelvis, a case that underscores the potential importance of both magnetic
resonance imaging (MRI) and bone marrow biopsy in establishing the diagnosis.
Additionally, we report the interval resolution of bony disease by MRI following
glucocorticoid treatment.
PMID- 17041485
TI - Resource-Based Relative Value Scale (RBRVS): a useful tool for practice analysis.
AB - This system determines Medicare reimbursement in the USA but also may provide
information to help analyze your practice. Since being implemented in 1992, the
Resource- Based Relative Value Scale (RBRVS) has been the basis of all physician
reimbursement from Medicare and increasingly is being used by other third-party
payers to determine physician payments. The development of the RBRVS dates back
to the 1980s and has evolved to the current system. Besides its use in physician
reimbursement, by virtue of its nationwide usage, RBRVS has become a tool by
which physicians can compare practice volume and efficiency, both with respect to
other practices and within a single practice, to compare individual physicians.
Although seemingly complex, the RBRVS provides a useful tool for physicians to
understand their productivity, contracting, and reimbursement.
PMID- 17041486
TI - 85-year-old retired welder.
PMID- 17041487
TI - Successful treatment of a patient with refractory adult-onset still disease with
anakinra.
PMID- 17041488
TI - A pilot trial of external Qigong therapy for arthritis.
PMID- 17041489
TI - Surgical anatomy of microneurosurgical sulcal key points.
AB - OBJECTIVE: The brain sulci constitute the main microanatomic delimiting landmarks
and surgical corridors of modern microneurosurgery. Because of the frequent
difficulty in intraoperatively localizing and visually identifying the brain
sulci with assurance, the main purpose of this study was to establish
cortical/sulcal key points of primary microneurosurgical importance to provide a
sulcal anatomic framework for the placement of craniotomies and to facilitate the
main sulci intraoperative identification. METHODS: The study was performed
through the evaluation of 32 formalin-fixed cerebral hemispheres of 16 adult
cadavers, which had been removed from the skulls after the introduction of
plastic catheters through properly positioned burr holes necessary for the
evaluation of cranial-cerebral relationships. Three-dimensional anatomic and
surgical images are displayed to illustrate the use of sulcal key points.
RESULTS: The points studied were the anterior sylvian point, the inferior
rolandic point, the intersection of the inferior frontal sulcus with the
precentral sulcus, the intersection of the superior frontal sulcus with the
precentral sulcus, the superior rolandic point, the intersection of the
intraparietal sulcus with the postcentral sulcus, the superior point of the
parieto-occipital sulcus, the euryon (the craniometric point that corresponds to
the center of the parietal tuberosity), the posterior point of the superior
temporal sulcus, and the opisthocranion, which corresponds to the most prominent
point of the occipital bossa. These points presented regular neural and cranial
cerebral relationships and can be considered consistent microsurgical cortical
key points. CONCLUSION: These sulcal and gyral key points can be particularly
useful for initial intraoperative sulci identification and dissection. Together,
they compose a framework that can help in the understanding of hemispheric lesion
localization, in the placement of supratentorial craniotomies, as landmarks for
the transsulcal approaches to periventricular and intraventricular lesions, and
in orienting the anatomic removal of gyral sectors that contain infiltrative
tumors.
PMID- 17041490
TI - An anatomical evaluation of the mini-supraorbital approach and comparison with
standard craniotomies.
AB - OBJECTIVE: To compare anatomically the surgical exposure provided by pterional
(PT), orbitozygomatic (OZ), and minisupraorbital (SO) craniotomies. METHODS:
Seven sides of six fixed cadaver heads injected with silicone were used. The mini
SO craniotomy followed by the PT and OZ approaches were performed sequentially.
The bony flaps were attached with miniplates and screws, allowing easy conversion
between the approaches. A frameless stereotactic device was used to calculate an
area of surgical exposure and the angles of approach for six different anatomic
targets. An image guidance system was used to demonstrate the limits of the
surgical exposure for each technique. RESULTS: No significant differences were
observed in the total area of surgical exposure when comparing the mini-SO (A =
1831.2 +/- 415.3 mm), PT (A = 1860.0 +/- 617.2 mm), and OZ approaches (A = 1843.3
+/- 358.1 mm; P > 0.05). Angular exposure was greater for the OZ and PT
approaches than for the mini-SO approach, either in the vertical and horizontal
axes, considering all of the six targets studied (P < 0.05). Except for the
distal segment of the ipsilateral sylvian fissure, no practical differences in
the limits of the exposure were detected. CONCLUSION: The mini-SO approach may
offer a similar surgical working area compared with that provided by standard
craniotomies and constitutes an excellent alternative to the OZ and PT
craniotomies in selected patients. Selection should not be based primarily on the
area to be exposed, but rather on the working angles that are anticipated to be
required. The key point is to use the most adequate technique for a particular
patient, rather than using a one-size-fits-all approach for all patients.
PMID- 17041491
TI - Gray matter overlying anterior basal temporal sulci as an intraoperative landmark
for locating the temporal horn in amygdalohippocampectomies.
AB - OBJECTIVE: Use of the gray matter overlying the anterior portions of the
occipitotemporal and rhinal sulci as an intraoperative landmark for locating the
temporal horn during amygdalohippocampectomies approached by the superior or
lateral surface of the temporal lobe. METHODS: The presence of occipitotemporal
and rhinal sulci was analyzed in the magnetic resonance imaging scans of 165
patients who subsequently underwent mesial temporal resections, focusing on
coronal slices up to 4 cm from the temporal pole. These sulci were used during
surgery to locate the temporal horn in 150 surgeries. Five adult cadaveric heads
whose vessels were perfused with colored silicone were used for photography.
RESULTS: These sulci are the principal sulci of the anterior basal temporal lobe.
They were present in 154 out of 165 and 165 out of 165 patients, respectively.
When approaching mesial temporal structures from the superior or lateral surface
of the temporal lobe, dissection is initially performed through the white matter
toward the floor of the middle fossa until the gray matter overlying an anterior
basal sulcus is encountered. Dissection continues medially and superiorly from
the top of the gray matter until the temporal horn is entered. CONCLUSION: Gray
matter overlying these sulci leads toward the anterior portion of the floor of
the temporal horn and constitutes a landmark for locating the temporal horn.
However, only the rhinal sulcus was always present. When both are present, the
gray matter overlying the occipitotemporal sulcus is a reliable landmark. These
landmarks are most suitable for mesial temporal resections without significant
displacement of the temporal horn.
PMID- 17041492
TI - Meyer's loop and the optic radiations in the transsylvian approach to the
mediobasal temporal lobe.
AB - OBJECTIVE: In the transsylvian approach to the mediobasal temporal structures,
the temporal horn is approached through the floor of the sylvian fissure. The
anterior bundle of the optic radiations (Meyer's loop) courses between the floor
of the sylvian fissure and roof of the temporal horn and could be damaged in this
approach. This study was designed to define the route through the floor of the
sylvian fissure least likely to damage the optic pathways. METHODS: Meyer's loop
was dissected by applying Klingler's fiber dissection technique in 10 formalin
fixed human hemispheres. Several measurements quantified the relationship of the
Meyer's loop to surgically important structures. RESULTS: This study identified a
triangular safe area below the floor of the sylvian fissure through which the
temporal horn could be accessed in the transsylvian approach with a low risk of
damaging the optic radiations. An incision in the floor of the sylvian fissure
directed downward at the level of limen insula and the adjacent 5 mm of the
inferior insular sulcus would avoid the optic radiations. An incision directed
straight downward 10, 15, and 20 mm behind the limen in the inferior insular
sulcus would cross Meyer's loop and would need to be directed downward and
medially as much as 80 degrees from the sagittal plane to avoid Meyer's loop.
CONCLUSION: In the transsylvian approach to the temporal horn, incisions at the
level of the limen, or adjacent 5 mm of the inferior insular sulcus, are less
likely to damage Meyer's loop and the optic radiations than more posterior
incisions along the inferior insular sulcus. Incision at this safe level commonly
opens into the amygdala, a portion of which is removed to provide entry into the
temporal horn for removal of the mediobasal structures.
PMID- 17041493
TI - The endoscopic endonasal approach to the lateral recess of the sphenoid sinus via
the pterygopalatine fossa: comparison of endoscopic and radiological landmarks.
AB - OBJECTIVE: The endoscopic endonasal approach offers the opportunity to reach the
pterygopalatine fossa, the lateral recess of the sphenoid sinus, and other areas
of the cranial base through a minimally invasive approach. This study compares
the anatomy of these areas when observed through an endoscopic endonasal view
with the anatomy of the same regions as they appear in computed tomographic
scans. The aim was to identify and correlate the corresponding anatomic
structures, providing the surgeons with anatomic landmarks to guide them when
operating in these areas through an endoscopic endonasal approach. METHODS: An
anatomic dissection of six fixed cadaver heads was performed by an endoscopic
endonasal approach. A step-by-step comparison of endoscopic and radiological
images was made to identify the landmarks of the surgical field. RESULTS: The
step-by-step comparison of endoscopic and radiological images acquired during the
endoscopic endonasal approach to the lateral recess of the sphenoid sinus via the
pterygopalatine fossa allowed the identification of all the relevant anatomic
landmarks of the procedure. CONCLUSION: The endoscopic endonasal approach via the
pterygopalatine fossa offers direct, minimally invasive access to the lateral
recess of the sphenoid sinus, which can be monitored in each phase through
consistent radiological imagery.
PMID- 17041494
TI - The supratonsillar approach to the inferior cerebellar peduncle: anatomy,
surgical technique, and clinical application to cavernous malformations.
AB - OBJECTIVE: To introduce the supratonsillar approach, an approach that traverses
the tonsillobiventral fissure in a trajectory over the cerebellar tonsil to the
inferior cerebellar peduncle, and to demonstrate the utility of this approach for
resecting peduncular cavernous malformations. METHODS: Anatomy of the cerebellar
tonsil and surrounding fissures, arteries, and veins are reviewed using cadaveric
brain specimens. The surgical approach uses the three-quarter prone position, a
suboccipital craniotomy, and wide splitting of the tonsillobiventral fissure.
RESULTS: Of our experience with 171 patients with cavernous malformations, six
patients had lesions in the inferior cerebellar peduncle that were resected using
the supratonsillar approach. All cavernous malformations were removed completely
and no patients experienced surgical complications or new deficits. CONCLUSION:
The supratonsillar approach differs from the transvermian and telovelar
approaches to the fourth ventricle, with a more superolateral trajectory that
leads instead to the inferior cerebellar peduncle. By splitting the
tonsillobiventral fissure and mobilizing the tonsil inferomedially, the point of
access to the lesion is deepened and transgression of normal cerebellar tissue is
minimized. This elegant approach is ideally suited to the removal of cavernous
malformations.
PMID- 17041495
TI - Extradural anterior clinoidectomy as an alternative approach for optic nerve
decompression: anatomic study and clinical experience.
AB - OBJECTIVE: We introduce pterional craniotomy extradural anterior clinoidectomy as
a new alternative approach for optic nerve decompression in patients with
traumatic optic neuropathy. METHODS: Intracranial structures pertinent to
pterional craniotomy extradural anterior clinoidectomy were carefully studied in
10 dry craniums and 10 cranial bases with dura mater. Important parameters of
these structures were measured. Stepwise dissections simulating pterional
craniotomy extradural anterior clinoidectomy were performed in 20 cadaver heads
bilaterally. Pterional craniotomy extradural anterior clinoidectomy was then
applied to 12 patients (13 eyes) with traumatic optic neuropathy and severe
visual dysfunction. RESULTS: The anatomic features and their variations of optic
canal, ophthalmic artery, falciform ligament, and Zinn's ring (annular tendon)
were studied and measured in detail. Extensive opening of the optic canal and
optic nerve sheath was successfully achieved in all 12 patients without major
surgical complications. Significant visual acuity improvement occurred in eight
(nine eyes) out of our 12 patients after surgery. The surgical techniques and
advantages of pterional craniotomy extradural anterior clinoidectomy for optic
nerve decompression are presented and discussed in detail. CONCLUSION: Pterional
craniotomy extradural anterior clinoidectomy is a promising new alternative
approach for optic nerve decompression in patients with traumatic optic
neuropathy.
PMID- 17041496
TI - The pterional-transsylvian approach: an analytical study.
AB - OBJECTIVE: Splitting of the sylvian fissure (SF) improves exposure with the
pterional (PT) approach. Traditionally, the choice of whether or not to split the
SF and how far to open it has depended on the neurosurgeon's experience and
preference rather than on quantifiable data. We undertook this study to evaluate
the effects of progressive splitting of the SF on surgical exposure with the PT
approach. METHODS: A PT craniotomy was performed on nine sides of cadaver heads.
Splitting the SF was divided into four steps: 1) dissection of the basal
cisterns, 2) dissection of the sphenoidal compartment, 3) dissection of the
operculoinsular compartment to the anterior ascendant ramus, and 4) dissection
progressing 2.0 cm distal to the anterior ascendant ramus. The degree of the
retraction and the relative position of the brain retractors were kept constant.
After each step, we used a computerized tracking system to measure the area of
surgical exposure of the circle of Willis, the angles of approach to the carotid
bifurcation, and the distance between the frontal lobe and skull base. RESULTS:
Exposure of the circle of Willis, angles of approach to the carotid bifurcation,
and linear distance between the frontal lobe and skull base all increased
significantly as splitting of the SF progressed from Steps 1 to 2 and from Steps
2 to 3. There was no significant difference between Steps 3 and 4. CONCLUSION:
Exposure of the basal cisterns and circle of Willis by the PT approach is
optimized when dissection of the SF reaches the anterior ascendant ramus. Further
splitting of the SF provides no additional gain.
PMID- 17041497
TI - The subtemporal interdural approach to dumbbell-shaped trigeminal schwannomas:
cadaveric prosection.
AB - OBJECTIVE: Successful resection of dumbbell-shaped trigeminal schwannomas via a
subtemporal interdural approach requires an understanding of both the anatomy
related to the bone dissection of the petrous apex (Kawase's triangle or
quadrilateral) and meningeal anatomy. We studied the meningeal anatomy related to
this approach and describe the dural incisions and stepwise mobilization.
METHODS: Meningeal anatomy around Meckel's cave and porus trigeminus was examined
during the subtemporal interdural anterior transpetrosal approach in both sides
of 15 cadaveric heads. Histological study of the Meckel's cave region was
performed in two cadaveric heads. RESULTS: The Gasserian ganglion and trigeminal
roots have two layers of dura propria on their dorsolateral surface: an inner
layer from the posterior fossa dura propria that constitutes the dorsolateral
wall of Meckel's cave and an outer layer from the dura propria of the middle
fossa. The cleavage plane between these two layers continues distally as the
cleavage plane between the epineural sheaths of the trigeminal divisions and the
dura propria of the middle fossa. This cleavage plane serves as the anatomic
landmark for the interdural exposure of the contents of Meckel's cave. The
superior petrosal sinus is sectioned at the medial aspect of Kawase's triangle
and reflected along with the porus trigeminus roof. CONCLUSION: Understanding the
critical meningeal architecture in and around Meckel's cave allows experienced
cranial neurosurgeons to develop a subtemporal interdural approach to dumbbell
shaped trigeminal schwannomas that effectively converts a multiple-compartment
tumor into a single-compartment tumor. Dural incisions and stepwise mobilization
complements our previous description of the bony dissection for this approach.
PMID- 17041498
TI - Microsurgical approaches to the medial temporal region: an anatomical study.
AB - OBJECTIVE: To describe the surgical anatomy of the anterior, middle, and
posterior portions of the medial temporal region and to present an anatomic-based
classification of the approaches to this area. METHODS: Twenty formalin-fixed,
adult cadaveric specimens were studied. Ten brains provided measurements to
compare different surgical strategies. Approaches were demonstrated using 10
silicon-injected cadaveric heads. Surgical cases were used to illustrate the
results by the different approaches. Transverse lines at the level of the
inferior choroidal point and quadrigeminal plate were used to divide the medial
temporal region into anterior, middle, and posterior portions. Surgical
approaches to the medial temporal region were classified into four groups:
superior, lateral, basal, and medial, based on the surface of the lobe through
which the approach was directed. The approaches through the medial group were
subdivided further into an anterior approach, the transsylvian transcisternal
approach, and two posterior approaches, the occipital interhemispheric and
supracerebellar transtentorial approaches. RESULTS: The anterior portion of the
medial temporal region can be reached through the superior, lateral, and basal
surfaces of the lobe and the anterior variant of the approach through the medial
surface. The posterior group of approaches directed through the medial surface
are useful for lesions located in the posterior portion. The middle part of the
medial temporal region is the most challenging area to expose, where the approach
must be tailored according to the nature of the lesion and its extension to other
medial temporal areas. CONCLUSION: Each approach to medial temporal lesions has
technical or functional drawbacks that should be considered when selecting a
surgical treatment for a given patient. Dividing the medial temporal region into
smaller areas allows for a more precise analysis, not only of the expected
anatomic relationships, but also of the possible choices for the safe resection
of the lesion. The systematization used here also provides the basis for
selection of a combination of approaches.
PMID- 17041499
TI - Increasing exposure of the petrous internal carotid artery for revascularization
using the transzygomatic extended middle fossa approach: a cadaveric morphometric
study.
AB - OBJECTIVE: When internal carotid artery (ICA) sacrifice is planned in the
management of difficult tumors or aneurysms at the cranial base, the petrous ICA
may be a useful site for anastomosis for interpositional vascular bypass.
However, exposure of the artery and performing an anastomosis in this region may
be technically challenging because of the narrow working corridor. The authors
describe a transzygomatic extended middle fossa approach that maximizes the
exposure of the petrous ICA for performing the difficult anastomosis. METHODS:
Bilateral dissections were performed on eight silicone-injected cadaveric head
specimens. Exposure of the entire petrous ICA (horizontal segment, genu, and
vertical segment) using the transzygomatic extended middle fossa approach was
performed by the following steps. A frontotemporal craniotomy was performed
followed by a zygomatic osteotomy. The temporal lobe dura was elevated
extradurally to expose the posterior cavernous sinus and floor of the middle
fossa. The middle fossa rhomboid was identified, which is bordered by V3
anteriorly, the GSPN laterally, the arcuate eminence posteriorly, and the petrous
edge medially. Bone drilling was performed in the middle fossa rhomboid and
Glasscock's triangle with care not to violate the cochlea. The horizontal and
vertical segments of the petrous ICA were skeletonized entirely and mobilized
from carotid canal. The V3 segment of the trigeminal nerve was retracted
anteriorly to obtain more distal exposure of the ICA. An osteoplastic bone flap
of the middle fossa floor lateral to the ICA was removed to increase the working
space. A morphometric analysis was performed, quantifying the petrous ICA
exposure, the surgical working corridor, and the angles of exposure. RESULTS: On
average, the length of the horizontal petrous ICA exposed was 9.2 +/- 1.0 mm
(range, 8.0-11.0 mm). Anterior retraction of V3 provided an additional 4.3 +/-
0.4 mm of carotid exposure (46.7% increase; P < 0.05). The length of the genu was
on average 3.6 +/- 0.4 mm (range, 3.0-4.0 mm), and the length of the vertical
segment of the petrous ICA was 13.1 +/- 2.0 mm (range, 10.0-15.0 mm). The average
depth of the petrous ICA from the outer surface of the temporal bone was 30.6 +/-
1.1 mm (range, 30.0-33.0 mm) at the V3-ICA junction and 27.2 +/- 0.7 mm (range,
26.0-28.0 mm) at the ICA genu. The average diameter of the inner working corridor
was 24.2 +/- 3.0 mm (range, 21.5-30.0 mm). Removal of the zygoma increased the
outer working corridor from an average distance of 24.4 +/- 3.8 mm to 33.4 +/-
3.4 mm (36.9% increase in exposure; P < 0.05). The average angle of exposure was
66.5% greater (P < 0.05) with zygomatic arch removal (39.3 +/- 4.9 degrees) than
without zygomatic arch removal (23.6 +/- 2.7 degrees). CONCLUSION: The
transzygomatic extended middle fossa approach provides a wide surgical corridor
for maximal exposure of the petrous ICA with minimized temporal lobe retraction.
This large exposure facilitates vascular anastomoses at the petrous ICA and
provides working room to maneuver instruments. The middle fossa rhomboid is a key
landmark to identify the petrous ICA and to avoid neuro-otologic structures.
PMID- 17041500
TI - "Target bypass": a method for preoperative targeting of a recipient artery in
superficial temporal artery-to-middle cerebral artery anastomoses.
AB - OBJECTIVE: To introduce a method for preoperative targeting of a proper recipient
artery in superficial temporal artery-to-middle cerebral artery anastomosis.
METHODS: Six operations for superficial temporal artery-to-middle cerebral artery
anastomosis in four patients with moyamoya disease or moyamoya-like disease and
two operations in two patients with atherosclerotic cerebrovascular occlusive
disease accompanied by coronary artery stenosis were performed using our method.
Before surgery, a 3-Tesla magnetic resonance imaging study was performed with
axial T1-weighted three-dimensional magnetization-prepared rapid acquisition
gradient-echo sequences and three-dimensional time-of-flight magnetic resonance
angiography. Data on quantitative regional cerebral blood flow were obtained by
iodine-123-labeled N-isopropyl-iodoamphetamine single-photon emission computed
tomography or positron emission computed tomography. The magnetic resonance
angiography and regional cerebral blood flow data sets were registered with the
magnetization-prepared rapid acquisition gradient-echo data set by means of the
coregistration function of the SPM2 software. We examined the arteries located on
or near the cortex where the regional cerebral blood flow had significantly
decreased and used the coregistered data set and MRIcro software to select the
cortical artery with the largest diameter as the target recipient artery. At the
surgery, the data sets were applied to the neuronavigation system and the actual
site of the target was confirmed in the operation before scalp incision. The
superficial temporal artery was anastomosed with the target through a small
craniotomy. RESULTS: Successful bypass surgery to the target was confirmed in all
cases. CONCLUSION: The "target bypass" method might be effective for cases with
moyamoya disease or for cases requiring surgery through a small craniotomy.
PMID- 17041501
TI - Treatment of giant and large internal carotid artery aneurysms with a high-flow
replacement bypass using the excimer laser-assisted nonocclusive anastomosis
technique.
AB - OBJECTIVE: To define the clinical value of the high-flow replacement bypass using
the excimer laser-assisted nonocclusive anastomosis technique in the treatment of
patients with a noncoilable, nonclippable giant or large intracranial aneurysm of
the internal carotid artery (ICA). METHODS: We studied 34 patients with a giant
intracranial aneurysm of the ICA proximal to its bifurcation who were treated
with an extracranial-intercranial high-flow replacement bypass in our hospital
between 1999 and 2004. We retrospectively collected data for patient
characteristics, operative aspects, complications, and functional health scores
using the modified Rankin scale. Long-term data were updated by questionnaire and
telephone survey. Mean long-term follow-up period was 3.3 years (range, 0.6-5.6
yr). RESULTS: We were able to construct a patent bypass in 33 out of 34 patients
(97%). In six patients (17%), we needed two bypass attempts. In one patient (3%),
the bypass was technically impossible. After bypass construction, we occluded the
ICA during or after surgery in 32 patients (94%), causing aneurysm thrombosis in
all of these patients. A fatal complication occurred in two patients (6%) before
we could occlude the ICA. A nonfatal complication occurred in seven patients
(21%). In the long term, 25 patients (74%) had a favorable outcome and 27
patients (79%) were independent (modified Rankin scale, <3). CONCLUSION: This
study shows that the excimer laser-assisted nonocclusive anastomosis high-flow
replacement bypass, which provides maximum brain protection because of its
nonocclusive character, is a reliable and effective method to treat these
otherwise untreatable patients.
PMID- 17041502
TI - Surgical management of hypothalamic hamartomas with epilepsy: the
stereoendoscopic approach.
AB - OBJECTIVE: Hypothalamic hamartomas (HHs) require surgical treatment in patients
presenting with refractory epilepsy. METHODS: The authors report on a single
center series of 33 patients (24 males, 9 females) who underwent surgery between
January 1997 and April 2004. They experienced several types of seizure (gelastic,
tonic, partial, atonic, generalized tonic-clonic, dacrystic, infantile spasm,
mental retardation, and behavioral and endocrinological abnormalities). Forty
nine interventions were carried out. Every patient, with the exception of the
first, underwent hamartoma disconnection (pterional approach, six patients;
endoscopy, 15 patients; both, 11 patients). The endoscopic approach was carried
out with a frameless stereotactic system to enhance feasibility and efficacy of
the disconnecting procedure. RESULTS: Surgery-related neurological complications
occurred in two patients, both after a pterional microsurgical approach.
Furthermore, two patients experienced panhypopituitarism and one patient
experienced transitory central insipid diabetes. All patients but one showed
recovery or considerable improvement of their epilepsy (Engel Class 1, 48.5%;
Engel Class 2, 3%; Engel Class 3, 45.5%; mean follow-up duration, 1 yr 7 mo).
CONCLUSION: According to the proposed classification of sessile HH into four
types, the best candidates for endoscopic disconnection are Type 2 and Type 3
HHs. In the present series, 90% of patients affected by Type 2 HH became seizure
free and the remaining 10% improved; of those with Type 3 HH at presentation,
35.3% recovered and 60% improved. Neuropsychological and endocrinological test
results showed improvement in many patients. Data from our series demonstrate
that frameless stereotactic endoscopic disconnection should be considered as the
treatment of choice in the presence of favorable anatomic conditions.
PMID- 17041503
TI - Orthogonal interlocking tandem clipping technique for the reconstruction of
complex middle cerebral artery aneurysms.
AB - OBJECTIVE: Complex aneurysms arising at the middle cerebral artery (MCA)
bifurcation frequently present a microsurgical challenge to effectively
obliterate while maintaining patency of the distal MCA branches. These aneurysms
are often multilobed, with their long axis aligned with the long axis of the M1
trunk, placing the dome of the aneurysm in the surgeons' line of sight,
preventing an unobstructed view of the entire bifurcation and proximal M1
segment. MCA aneurysms often have a broad neck, splaying the bifurcation. An
orthogonal interlocking tandem clipping technique, maximizing the use of
fenestrated aneurysm clips, is presented as a means to completely obliterate the
aneurysm and simultaneously "reconstruct" the MCA bifurcation. CLINICAL
PRESENTATIONS AND INTERVENTION: Fifteen complex MCA aneurysms were treated using
an interlocking tandem clipping technique. In its simplest application, the
blades of the initial aneurysm clip are incorporated into the fenestration of the
second clip. Obliteration of the residual aneurysm is achieved with the blades of
the second, fenestrated clip. RESULTS: Satisfactory aneurysm obliteration and
reconstruction of the MCA bifurcation was achieved in all cases using this
technique, with excellent neurological outcomes. CONCLUSION: Morphologically
complex multilobed MCA aneurysms can be effectively clipped with "reconstruction"
of the normal vascular anatomy using a tandem interlocking clipping technique. A
fenestrated clip is used to incorporate the blades of the initial clip, while
obliterating the remainder of the aneurysm.
PMID- 17041504
TI - Submandibular-infratemporal interpositional carotid artery bypass for cranial
base tumors and giant aneurysms.
AB - OBJECTIVE: Cerebral revascularization is an important strategy in the surgical
management of some complex cranial base tumors and unclippable aneurysms. A high
flow bypass may be necessary in planned carotid occlusion or sacrifice. The
cervical-to-supraclinoid internal carotid artery bypass or cervical carotid-to
middle cerebral artery bypass are useful procedures to bypass lesions at the base
of the cranium. We describe technical modifications of the submandibular
infratemporal interpositional saphenous vein (or radial artery) graft bypass
technique specifically designed to avoid removal of the zygoma. METHODS: The
saphenous vein or radial artery interpositional graft is tunneled through a burr
hole created in the floor of the middle fossa via a submandibular-infratemporal
route avoiding removal of zygoma and attachments of the masseter or temporalis
muscles. RESULTS: The technique is demonstrated in one patient with removal of a
malignant cavernous sinus tumor and in another patient with an unclippable giant
carotid bifurcation aneurysm. CONCLUSION: The advantages of this approach include
preservation of the facial anatomy and creation of a short and safe route for
passage of the saphenous vein or radial artery graft.
PMID- 17041505
TI - Minimally invasive transmuscular pedicle screw fixation of the thoracic and
lumbar spine.
AB - OBJECTIVE: This study assessed the feasibility and safety of percutaneous
posterior pedicle screw fixation for instabilities of the thoracic and lumbar
spine, using standard instruments designed for the open approach and fluoroscopy.
METHODS: All patients who underwent percutaneous posterior pedicle screw fixation
of the thoracic and lumbar spine were studied retrospectively. Charts and
operative notes were analyzed for epidemiological data, underlying spinal
pathological features, and indications for stabilization, stabilized segments,
number of implanted pedicle screws, surgical time, and complications.
Postoperative computed tomographic scans were analyzed for screw position.
RESULTS: From May 2002 through May 2005, 115 internal fixators were implanted
percutaneously in 104 patients. A total of 488 pedicle screws were implanted,
stabilizing 1 to 5 spinal motion segments. Median surgical time was 93 minutes.
On postoperative computed tomographic scans, 87% of screw positions were rated
good, 10% were rated acceptable, and 3% were rated unacceptable. A total of 11
revisions were necessary, 9 for misplaced screws and 2 for loosening of anchor
bolts. Only two of the patients experienced new clinical symptoms (i.e.,
radicular pain) because of screw misplacement. No patients experienced new
neurological deficits or other surgery-related morbidity. CONCLUSION: This study
shows that percutaneous internal pedicle screw fixation using standard
instruments is feasible and safe for posterior stabilization of the thoracic and
lumbar spine. It is a straightforward alternative for open approaches or
minimally invasive ones using navigation in conjunction with customized
instruments. Accuracy of screw placement is similar to that reported for other
techniques.
PMID- 17041506
TI - Intraoperative cortical surface characterization using laser range scanning:
preliminary results.
AB - OBJECTIVE: To present a novel methodology that uses a laser range scanner (LRS)
capable of generating textured (intensity-encoded) surface descriptions of the
brain surface for use with image-to-patient registration and improved cortical
feature recognition during intraoperative neurosurgical navigation. METHODS: An
LRS device was used to acquire cortical surface descriptions of eight patients
undergoing neurosurgery for a variety of clinical presentations. Textured surface
descriptions were generated from these intraoperative acquisitions for each
patient. Corresponding textured surfaces were also generated from each patient's
preoperative magnetic resonance tomograms. Each textured surface pair (LRS and
magnetic resonance tomogram) was registered using only cortical surface
information. Novel visualization of the combined surfaces allowed for
registration assessment based on quantitative cortical feature alignment.
RESULTS: Successful textured LRS surface acquisition and generation was performed
on all eight patients. The data acquired by the LRS accurately presented the
intraoperative surface of the cortex and the associated features within the
surgical field-of-view. Registration results are presented as overlays of the
intraoperative data with respect to the preoperative data and quantified by
comparing mean distances between cortical features on the magnetic resonance
tomogram and LRS surfaces after registration. The overlays demonstrated that
accurate registration can be provided between the preoperative and intraoperative
data and emphasized a potential enhancement to cortical feature recognition
within the operating room environment. Using the best registration result from
each clinical case, the mean feature alignment error is 1.7 +/- 0.8 mm over all
cases. CONCLUSION: This study demonstrates clinical deployment of an LRS capable
of generating textured surfaces of the surgical field of view. Data from the LRS
was registered accurately to the corresponding preoperative data. Visual
inspection of the registration results was provided by overlays that put the
intraoperative data within the perspective of the whole brain's surface. These
visuals can be used to more readily assess the fidelity of image-to-patient
registration, as well as to enhance recognition of cortical features for
assistance in comparing the neurotopography between magnetic resonance image
volume and physical patient. In addition, the feature-rich data presented here
provides considerable motivation for using LRS scanning to measure deformation
during surgery.
PMID- 17041507
TI - Axially dynamic implants for stabilization of the cervical spine.
AB - OBJECTIVE: Subsidence is a naturally occurring process that is observed during
aging and after spine surgery. Rigid cervical spine instrumentation is excellent
for stabilizing the spine. These devices, however, also retard subsidence after
surgery. Thus, the implant carries much of the axial load, rather than sharing
the axial load with the bone graft. This results in an increased incidence of
construct failures, pseudoarthrosis, or both, which often occur late in the
postoperative course. METHODS: In contrast, dynamic implants allow normal
(natural) subsidence to occur, while effectively stabilizing the spine by
preventing translation, rotation, and angular deformation. Load sharing, which
works with, instead of against, the normal biology of bone healing, occurs with
axially dynamic implants, resulting in more robust and earlier fusions. RESULTS:
Diminished incidences of construct failures have been reported with dynamic
implants. CONCLUSION: Dynamic implants seem to be the system of choice for
ventral cervical stabilization in selected patients.
PMID- 17041508
TI - Surgical pitfalls of an ultrasonic bone curette (SONOPET) in spinal surgery.
AB - OBJECTIVE: We report our experience with the SONOPET ultrasonic bone curette.
METHODS: Between September 2001 and July 2005, 546 patients underwent microscopic
spinal surgeries using a high-speed drill and the SONOPET instrument. RESULTS: We
encountered operative complications thought to be attributable to the use of the
SONOPET in six patients (1.1%). There were five instances of dural puncture and
one spinal cord injury. All dural tears occurred when the dura mater was
aspirated into the tip of the SONOPET. None of the affected patients developed
postoperative clinical complications because cerebrospinal fluid leakage was
avoided by appropriate closure. We think that the transient spinal cord injury
occurred because the vibration emanating from the SONOPET was transmitted
directly to the spinal cord. Some patients experienced damage to the epidural
venous plexus for reasons similar to those described above. CONCLUSION: SONOPET
facilitates the removal of bone in a narrow field, such as that encountered
during keyhole surgery. It aids in the removal of the lateral edge of bone and is
especially useful for expanding the foramen intervertebrale or opening the
lateral recess. However, its use is not without risk. To prevent dural tears and
venous plexus injury, we recommend that cotton be placed between the SONOPET and
important structures. To avoid spinal cord injury, we suggest that the SONOPET be
inserted horizontal with the dura mater to avoid the direct transmission of
vibrations emanating from the instrument to the spinal cord. SONOPET is suitable
for decompression on the lateral side, but not for decompression above the spinal
cord.
PMID- 17041509
TI - Frameless stereotactic cannulation of the foramen ovale for ablative treatment of
trigeminal neuralgia.
AB - OBJECTIVE: Ablative neurosurgical treatment of trigeminal neuralgia, including
percutaneous radiofrequency thermocoagulation, requires cannulation of the
foramen ovale. To maximize patient security and cannulation success, a frameless
stereotactic system was evaluated in a phantom study, a cadaveric study, and a
preliminary clinical trial. METHODS: Frameless stereotaxy using an optical
navigation system, an aiming device, and a noninvasive vacuum mouthpiece-based
registration and patient fixation technique was used for the targeting of a test
body based on 1-, 3-, and 5-mm axial computed tomographic slices and of the
foramen ovale in three cadavers and 15 patients based on 3-mm axial computed
tomographic slices. RESULTS: The mean normal (x/y) localization accuracy/standard
deviation (n = 360) was 1.31/0.67 mm (1-mm slices), 1.38/0.65 mm (3-mm slices),
and 1.84/0.96 mm (5-mm slices). Significantly better results were achieved with 1
and 3-mm slices when compared with 5-mm slices (P < 0.001). The foramen ovale (3
x 6 mm) was successfully cannulated at the first attempt in all cadavers and
patients, which indicates clinical localization accuracies better than 1.5 mm in
the anteroposterior and 3 mm in the medial-lateral directions. CONCLUSION: Based
on the noninvasive Vogele-Bale-Hohner vacuum mouthpiece, there is no need for
invasive head clamp fixation. Imaging, real laboratory simulation, and the actual
surgical intervention can be separated in time and location. The presented data
suggest that frameless stereotaxy is a predictable and reproducible procedure,
which may enhance patient security and cannulation success independent of the
surgeon's experience.
PMID- 17041510
TI - Recanalization of obstructed cerebrospinal fluid ventricular catheters using
ultrasonic cavitation.
AB - OBJECTIVE: Fifty percent of implanted cerebrospinal fluid (CSF) shunts fail
within 2 years, primarily because of obstruction of the proximal catheter.
Percutaneous techniques to reduce the morbidity of shunt revision are being
developed. The authors describe the development of a device that uses ultrasonic
cavitation to unblock ventricular catheters. METHODS: In collaboration with
Cybersonics, Inc. (Erie, PA), we designed, built, and tested a system that
produces low-frequency ultrasound (20-28 kHz). Extensional ultrasonic waves are
transmitted along a tapered wire (final diameter, approximately 0.8 mm) to the
tip, where cavitation is produced in a highly localized region. An in vitro model
of sheep choroid plexus occluding typical ventricular catheters was developed.
The device was safety tested in vivo in rat and pig brains by introducing the
device into shunt catheters inserted during simulated shunt surgery. A clinical
safety trial using the device to attempt to remove blocked and adherent
ventricular catheters has commenced. RESULTS: In the sheep choroid plexus model,
at least 90% of the occluded holes were unblocked in a few minutes, restoring
normal flow. There was no adverse effect of the device within shunt catheters
inserted into live animal brains. Four patients have undergone treatment with the
device at open CSF shunt surgery without adverse effect, and the device seems
effective at unblocking and freeing the occluded catheters. CONCLUSION:
Ultrasonic cavitation produced at the end of a fine wire that is introduced
percutaneously into a CSF shunt promises to be a useful technique for minimally
invasive proximal ventricular CSF shunt catheter revision.
PMID- 17041511
TI - Electrocautery-induced ignition of spark showers and self-sustained combustion of
onyx ethylene-vinyl alcohol copolymer.
AB - OBJECTIVE: Ethylene-vinyl alcohol copolymer mixed with micronized tantalum (Ta)
as radiopacifier (Onyx; Micro Therapeutics Inc., Irvine, CA) has emerged as a
useful liquid embolic agent for vascular malformations. We describe
intraoperative ignition of Onyx-embolized tissue and undertake an in vitro
investigation to reproduce and characterize this hazard. METHODS: Samples of
Onyx, Ta-depleted Onyx, Ta-n-butylcyanoacrylate (Ta-NBCA), and Ta powder were
exposed to monopolar and bipolar electrocautery in cut and coagulation modes at
different power settings to reproduce the intraoperative findings. Recordings of
sparking and combustion events were analyzed to characterize duration and
relative frequency. RESULTS: Spark showers and self-sustained combustion were
observed intraoperatively when an Onyx-embolized artery was coagulated with the
monopolar electrocautery. Sparking covered a radius greater than 10 cm, and
combustion lasted a median of 1.65 seconds (range, 0.3-12.3 s). Sparking and
sustained combustion were reproduced in vitro by both cut and coagulation
monopolar modes in Onyx casts and free Ta powder but not in samples of Ta
depleted Onyx or casts of Ta-NBCA. Ignition was similarly observed when using
bipolar electrocautery but only at higher energy settings. CONCLUSION:
Electrocautery use on tissue containing Onyx results in potentially dangerous
uncontrolled sparking and combustion in a process that is Ta dependent. It is
recommended that Ta-NBCA be used instead of Onyx in situations mandating the use
of a liquid embolic and high-energy electrocautery, pending the development of a
safer radiopacifier for use with ethylene-vinyl alcohol copolymer.
PMID- 17041512
TI - Hemorrhagic complications of external ventricular drainage.
AB - OBJECTIVE: Despite the widespread use of external ventricular drainage (EVD), the
frequency of associated hemorrhagic complications remains unclear. This
retrospective study examined the frequency of hemorrhagic complications of EVD
and attempted to discern associated risk factors. METHODS: Treatment records from
160 patients admitted during a 2.5-year period who required EVD placement were
reviewed. Indications for placement of EVD included acute complications of
cerebrovascular disease (n = 94), traumatic brain injury (n = 36), primary
hydrocephalus (n = 16), and tumor (n = 14). Patients received either a 3.0 or 2.5
mm outer diameter ventricular catheter (n = 82 and 78, respectively).
Postinsertion computed tomographic scans were obtained within 24 hours on all
patients and were analyzed for any new hemorrhage related to the ventricular
catheter. Patient age, sex, catheter type, and dimensions of hemorrhage were also
analyzed. RESULTS: The incidence of EVD-related hemorrhage was 33 +/- 0.04%.
However, the incidence of detectable change in the clinical neurological
examination was 2.5%. A significant proportion of EVD-related hemorrhages were
small (<4 cm), punctate, intraparenchymal hematomas. Patients with
cerebrovascular disease exhibited an increased incidence (39%) of hemorrhage. The
mean volume of intraparenchymal hemorrhage was larger in patients who received
the 2.5-mm ventricular catheter, as well as those admitted for cerebrovascular
disease. CONCLUSION: Hemorrhagic complications of EVD placement are more common
than previously suspected. Admitting diagnosis seems to have an effect on the
development of an associated hemorrhage and its size. Catheter gauge has an
effect on hematoma volume. Most of the hemorrhages seen on postinsertion computed
tomographic scans do not cause detectable changes in the clinical examination.
PMID- 17041513
TI - Extended bifrontal craniotomy for midline anterior fossa meningiomas:
minimization of retraction-related edema and surgical outcomes.
AB - OBJECTIVE: Meningiomas of the anterior cranial base can be approached with a
variety of techniques. The extended bifrontal approach is often thought to be
associated with increased morbidity because of the need for extensive removal of
the bone and longer surgical times. The authors have attempted to quantitate
retraction-related edema occurring after surgery to determine whether the extra
bone removal limits retraction and reduces the chance of brain injury. METHODS:
Charts were reviewed for patients who underwent extended bifrontal craniotomies
performed for meningiomas at the University of California, San Francisco, between
1997 and 2005. Magnetic resonance imaging scans obtained before and after surgery
were reviewed for brain edema as indicated by fluid-attenuated inversion
recovery/T2 abnormality and grouped into four categories: A, no edema; B, edema
restricted to the gyrus rectus; C, edema beyond the gyrus rectus; and D,
extensive bifrontal edema. RESULTS: Forty-five patients were identified. Fifty
four percent of patients had tumors with a diameter of more than 4 cm. Simpson
Grade 2 or 3 resection was achieved in 82% of patients, and the average operative
time was 12.3 hours. Vision outcome was favorable in 74% of patients. Extent of
fluid-attenuated inversion recovery abnormality remained unchanged in 87.5%, with
91% of patients in categories A or B edema remaining in those categories after
surgery. There were no infections and there were two cerebrospinal fluid leaks.
CONCLUSION: The extended bifrontal approach is a safe surgical procedure with
limited morbidity that the authors think: 1) prevents secondary brain injury from
excessive retraction; 2) offers great flexibility of view for the surgeon; and 3)
should be considered the preferred approach compared with the standard bifrontal
craniotomy for large tumors of the anterior cranial base.
PMID- 17041514
TI - Risk of damage to the endolymphatic sac and duct during removal of the posterior
meatal wall: an anatomic study.
AB - OBJECTIVE: With removal of the posterior meatal wall for intrameatal acoustic
neurinoma, preservation of the structures adjacent to the internal acoustic
meatus is important. The authors performed an anatomic study to clarify the risk
of damage to the endolymphatic sac and endolymphatic duct during this maneuver.
METHODS: Twenty-seven sides of adult temporal bone were examined. Distances
measured were between the posterior meatal lip and the upper limit of the
endolymphatic ledge, at the upper extent of the endolymphatic sac, and between a
reference line extending from the inferior margin of the internal acoustic meatus
posteriorly (parallel to the petrous ridge), simulating the inferior margin of
the drilling, and the upper limit of the endolymphatic ledge. Whether the latter
was located on or above the line was also recorded. After posterior meatal wall
drilling, the distance between the posterior meatal lip and the vestibular
aqueduct surrounding the endolymphatic duct and the depth of the structure from
the surface were assessed. RESULTS: The shortest distances between the posterior
meatal lip and the endolymphatic ledge and between the posterior meatal lip and
the vestibular aqueduct were 6.80 mm and 4.68 mm, respectively. The upper limit
of the endolymphatic ledge was present on or above the reference line in
approximately half of the specimens. CONCLUSION: During surgical maneuvers to
remove the posterior meatal wall, the occasional close proximity of the
endolymphatic sac and endolymphatic duct to the internal acoustic meatus should
be kept in mind. Preoperative radiological evaluation of anatomic relationships
is mandatory when preservation of hearing is the aim.
PMID- 17041515
TI - Complication avoidance in peripheral nerve surgery: preoperative evaluation of
nerve injuries and brachial plexus exploration--part 1.
AB - Complication avoidance during peripheral nerve surgery has received little
attention in the neurosurgical literature. The goal of our two-part review is to
discuss these possible complications, with this initial article highlighting the
pitfalls associated with pre- and intraoperative assessment of nerve injuries, as
well as the operative nuances used during brachial plexus exploration to minimize
complications.
PMID- 17041516
TI - Complication avoidance in peripheral nerve surgery: injuries, entrapments, and
tumors of the extremities--part 2.
AB - The goal of this two-part review is to discuss peripheral nerve surgery
complications, along with the techniques and principles used to prevent them. In
this second article, we concentrate on injuries, tumors, and entrapment of nerves
in the extremities, including carpal tunnel syndrome and ulnar nerve compression
at the elbow.
PMID- 17041517
TI - A method for calculating the exact angle required during pedicle subtraction
osteotomy for fixed sagittal deformity: comparison with the trigonometric method.
AB - OBJECTIVE: Pedicle subtraction osteotomy (PSO) has emerged as a powerful
procedure for correcting fixed sagittal deformity. There has only been one
attempt to quantify the magnitude of correction needed to restore sagittal
balance; the trigonometric method for calculating the desired PSO angle is an
approximation. We propose a method for calculating the exact angle required for
PSO and explore how this angle differs from that obtained via the trigonometric
method in illustrative cases. METHODS: We conducted a mathematical analysis of
the spine with application in illustrative cases. The trigonometric method
calculates the necessary angular correction at the axial level of the PSO, but
along the sacral vertical line. However, the angular measurement should take
place at the true axis of rotation, the apex of the PSO. Measurements were taken
from full-length standing x-rays, and both methods were explored. RESULTS: The
trigonometric method for calculating PSO angle is an exact measurement only if
the apex of the PSO site lies on the sacral vertical line. As the apex of the PSO
site moves anterior to that line, the trigonometric approximation underestimates
the actual angle. As the apex of the PSO moves posterior to that line, the
trigonometric approximation overestimates the actual angle. CONCLUSION: The
trigonometric method for calculating the PSO angle required for surgical
deformity correction is an approximation, but its validity in clinical practice
was confirmed by this study. The exact angle is obtained by a method centered on
the apex of the PSO site. Although the difference between these angles is small,
it is an important conceptual point for spine surgeons. Measurement of the exact
angle is easily performed and should replace the trigonometric method for
calculating the required PSO angle when standard digital measurement tools are
available.
PMID- 17041518
TI - 2-Hexyl cyanoacrylate (neuracryl M) embolization of cerebral arteriovenous
malformations.
AB - OBJECTIVE: Neuracryl M is a newly designed liquid embolic agent. In an attempt to
verify the safety and efficacy of neuracryl M, we participated in the PROVASIS
Trial, a pilot study using this agent in the preoperative treatment of cerebral
arteriovenous malformations (AVMs). Because the trial was prematurely terminated
by the sponsoring company because of financial considerations, we now present our
data as a single center series. METHODS: Between November 2002 and December 2003,
six patients were enrolled in the PROVASIS trial at our institution, and four of
these patients were randomized to treatment with neuracryl M. The patients were a
30-year-old man with a right frontal lobe AVM, a 20-year-old man with a right
cerebellar AVM, a 26-year-old woman with a midline cerebellar AVM, and a 47-year
old man with a left parietotemporal lobe AVM. All patients underwent AVM
embolization with neuracryl M, followed by definitive treatment, either open
surgery or radiosurgery. RESULTS: In each case, there were no permanent
complications, and blood loss was minimal. Follow-up imaging demonstrated either
complete AVM obliteration (open surgery) or substantial diminution in AVM size
(radiosurgery). CONCLUSION: Our data provide preliminary evidence supporting the
thesis that neuracryl M is a safe and effective liquid embolic agent for the
preoperative embolization of cerebral AVMs. Larger trials and continued
experience using this novel liquid embolic agent are warranted.
PMID- 17041519
TI - Intratumoral hydrogen peroxide injection during meningioma resection.
AB - OBJECTIVE: Meningiomas, although histologically benign, pose a particular
challenge to the neurosurgeon because of their extensive and exuberant
vascularity. They often bleed extensively during resection until separated from
their blood supply. There are a wide variety of hemostatic agents available to
the neurosurgeon. Most of these means of hemostasis involve some sort of
chemical, electrical, or compressive action. Although anecdotally known to be
useful, the use of hydrogen peroxide as an intracranial hemostatic agent in
meningioma surgery has not been formally reported. We report a technique of
meningioma resection that uses intratumoral hydrogen peroxide injection, reducing
the potential for blood loss and shortening resection times. METHODS: Seventy
five patients underwent resection of a meningioma using the direct intratumoral
H2O2 injection technique. The locations of these meningiomas included convexity
and cranial-based lesions. None of the patients underwent preoperative
endovascular embolization. RESULTS: The use of this technique greatly facilitated
the removal of these tumors. No evidence of air embolism occurred during Doppler
surveillance and no other significant side effects attributable to H2O2
application were observed. CONCLUSION: We demonstrate a previously unreported
technique of meningioma resection that uses direct intratumoral hydrogen peroxide
injection, potentially reducing blood loss, shortening resection times, and
obviating the need for preoperative embolization.
PMID- 17041520
TI - Stent placement for intracranial cysts by combined stereotactic/endoscopic
surgery.
AB - OBJECTIVE: The treatment of space-occupying cystic lesions includes percutaneous
cyst aspiration, marsupialization, percutaneous ventriculocystotomy, or Rickham
catheter implantation. In some patients, the cysts tend to recur and repeated
evacuations are necessary. The authors present a new treatment method with
internal drainage of cysts into the ventricular system using a balloon-mounted
vascular stent. METHODS: Six patients with cysts of low-grade gliomas, one with
monocystic craniopharyngioma, and one with suprasellar arachnoid cyst were
treated between September 2003 and May 2005. All patients were symptomatic after
multiple previous treatments. Stent implantations were performed under local
anesthesia in adults and under general anesthesia in children. In all patients,
the stereotactic frame and computed tomographic and magnetic resonance fusion
were used for an optimized approach. The treatment was performed in a
compassionate manner and the patients were informed about the off-label use of
the device. RESULTS: Stent placement was successful in all eight patients without
procedure-related complications. Improvement of clinical symptoms was seen in
seven out of eight patients. Seven out of eight cysts decreased in size within a
follow-up period of up to 23 months (mean, 17 mo; median, 18 mo; range, 6-23 mo).
The first patient showed recurrence of the tumor cyst 3 months after initial
treatment with a Herkulink stent (5 x 18 mm), followed by retreatment with an
Omnilink stent (6 x 28 mm; Guidant Corp., Santa Clara, CA). Stenting was
ineffective in one patient. CONCLUSION: Treatment of intracranial cystic lesions
by internal drainage is possible with the use of stent-assisted
ventriculocystostomy.
PMID- 17041521
TI - Intravascular ultrasound for intracranial angioplasty and stent placement:
technical case report.
AB - OBJECTIVE: Intravascular ultrasound (IVUS) imaging has been used extensively in
coronary artery interventions and has provided invaluable information for the
understanding and treatment of coronary arterial disease. We present here the
first description, to our knowledge, of IVUS-guided intracranial arterial
interventions in the clinical setting. CLINICAL PRESENTATION: Two patients
underwent intracranial angioplasty and stent placement with the assistance of
IVUS for the evaluation of their lesions. One patient underwent stenting to treat
an occlusive dissection of the left internal carotid artery that occurred during
arteriovenous malformation embolization. Another patient underwent angioplasty
and stenting for high-grade restenosis of a basilar artery atherosclerotic
lesion. RESULTS: Both patients underwent successful revascularization procedures.
The patient with the dissection had a small intraventricular and parenchymal
hemorrhage documented by computed tomography 4 hours after treatment, but did not
develop hydrocephalus or further hemorrhage. Both patients did well clinically
and had no permanent neurological deficits. IVUS provided important information
in terms of lesion evaluation, stent selection, and stent placement in each case.
CONCLUSION: IVUS of the intracranial circulation may assist the performance of
intracranial angioplasty and stenting. It provides useful information that can
affect clinical decisions. It may prove to be a valuable tool in clinical use and
enhance our understanding of vascular disease of the intracranial circulation, as
it has in the coronary circulation.
PMID- 17041522
TI - Coating the wall of an injured intracranial carotid artery during tumor removal
with n-butyl-2-cyanoacrylate: technical case report.
AB - OBJECTIVE: Carotid artery injury close to the clinoid process is difficult to
repair, and is even more so when the vessel is firmly attached to a calcified
tumor. We treated a patient with an intraoperative carotid lesion by coating the
vessel wall with n-butyl-2-cyanoacrylate (NBCA). CLINICAL PRESENTATION: A 7-year
old boy was referred to our clinic with a 3-month history of somnolence, apathy,
and headache. Neurological examination revealed bitemporal hemianopsia. The
cranial magnetic resonance imaging and computed tomographic scans showed a sellar
and suprasellar calcified mass with heterogeneous contrast enhancement, a cyst
component in the upper part of the tumor displaced upward and back from the
mesencephalic and diencephalic structures. INTERVENTION: The patient underwent a
pterional craniotomy. Using a microsurgical technique, the suprasellar part of
the craniopharyngioma was removed. In an attempt to dissect the calcified mass
from the carotid artery on the right side, the vessel was unintentionally
injured, followed by severe bleeding. Temporary occlusion and suturing of the
vessel was impossible because of the overlying hard mass. To avoid a permanent
occlusion, we decided to coat the injured artery wall with 100% NBCA. For this,
0.5 ml of NBCA was distributed on the surface of the injured segment and
surrounding subarachnoid space by injection through a needle. An excellent
hemostasis could be obtained immediately after coating. The patient woke up with
no new neurological deficits. A digital cerebral angiogram obtained a few days
after the procedure did not show vasospasm, stenosis, or pseudoaneurysm in the
supraclinoidal segment of the carotid artery. A magnetic resonance angiogram
obtained 3 years later showed a normal shape of the internal carotid artery and a
stable residual tumor without inflammatory signs. The child is now attending
school and is under hormonal therapy. CONCLUSION: For hemostatic purposes, the
technique of coating an injured arterial wall with NBCA may be useful in cases in
which a microsuture is impossible and a permanent artery occlusion is unwanted
because of a risk of an ischemic stroke. It could serve as a transitory measure
until a microsurgical bypass or the balloon test occlusion tolerance allow the
trapping of the affected artery.
PMID- 17041523
TI - An oblique paraspinal approach for intracanalicular disc herniations of the upper
lumbar spine: technical case report.
AB - OBJECTIVE: To present our experience of treating the central or paramedian disc
herniations of the upper lumbar levels through a paraspinal approach. CLINICAL
PRESENTATION: We present four patients with intracanalicular disc herniations at
the L1-L2 or L2-L3 level. All patients had unilateral or bilateral radicular leg
pain and motor weakness. TECHNIQUE: Considering the unique characteristics of the
upper lumbar spine, we performed the oblique paraspinal approach to expose the
central portion of disc and removed the herniated disc effectively.
Postoperatively, their symptoms were improved. There was no instability during
the follow-up period. CONCLUSION: The oblique paraspinal approach for the
treatment of central disc herniations at the upper lumbar levels is an effective
nonfusion technique that preserves most of the facet joint and provides a wide
surgical field.
PMID- 17041524
TI - Endoscope-assisted microvascular decompression for trigeminal neuralgia:
technical case report.
AB - OBJECTIVE: Microvascular decompression may fail to relieve trigeminal neuralgia
because a compressing vessel at the root entry zone may be overlooked during
surgery. Alternatively, effective decompression may not always be achieved with
the visualization provided by the microscope alone. We theorized that the
addition of an endoscope would improve the efficacy of microvascular
decompression. METHODS: We retrospectively reviewed microvascular decompression
of the trigeminal nerve in 114 patients. Before closure, the endoscope was used
to inspect the root entry zone. When visualization with the microscope was poor,
the endoscope was used to identify an aberrant vessel and to perform or improve
the subsequent decompression. RESULTS: Of 114 patients who underwent
microvascular decompression, 113 successfully underwent endoscopy. In 38 patients
(33%), endoscopy revealed arteries that were poorly seen (25%) or not seen at all
(8%) with the microscope. At a mean follow-up period of 29 months, the pain was
completely relieved in 112 patients (99.1%), all of whom were off medication.
Complications included trigeminal dysesthesias in nine patients and a wound
infection, partial hearing loss, and complete hearing loss in one patient each.
The overall complication rate was 9%. CONCLUSION: Endoscopy is a simple and safe
adjunct to microscopic exploration of the trigeminal nerve. The markedly improved
visualization increases the likelihood of identifying the offending vessel and
consequently of achieving satisfactory decompression of the nerve. Thus far, the
success rate has been high, and the complication profile is comparable to that of
other large series.
PMID- 17041525
TI - Unruptured intracranial aneurysms: the unreliability of clinical judgment, the
necessity for evidence, and reasons to participate in a randomized trial.
PMID- 17041526
TI - [Diffusion and perfusion MR imaging in cerebral lymphomas].
AB - Because of the increasing incidence of cerebral lymphoma, it is critical for
patient management to recognize the MR features of this disease. We present the
characteristic morphological and functional MRI features of this tumor. The
findings on MRI studies, including morphological, diffusion and perfusion
imaging, performed in 9 biopsy-proven cases of cerebral lymphoma with 13 lesions
are presented and analyzed, and are discussed in comparison with published
literature data. All patients underwent diffusion-weighted imaging with a single
shot echo-planar pulse sequence. Dynamic susceptibility-contrast MRI was
performed using a T2*-weighted gradient-echo echo-planar sequence after
intravenous injection of chelates of gadolinium at the rate of 6 ml/s and a
temporal resolution of 1 second. All cases of cerebral lymphoma appeared
hypointense or isointense on T1-weighted images and in 75% of cases iso- or
hypointense on T2-weighted images. All lesions enhanced except one in a patient
receiving steroid therapy. On diffusion-weighted images, tumours were
hyperintense with normal or decreased ADC values (0.717+/-0.152.10-3 mm2/sec,
range: 0.550-1.014) and an ADC ratio tumour/normal white matter of 0.974+/-0.190
(range: 0.768-1.410). On perfusion, the signal intensity-time curve of each
tumour showed a characteristic type of curve with a significant increase of the
signal intensity above the baseline and a low maximum relative cerebral blood
volume ratio (rCVBmax) of 1.43+/-0.64 (0.55-2.62). Due to their higher
cellularity, the lack of neoangiogenesis, and the increased permeability of the
blood-brain barrier related to the infiltration of blood vessels wall by
lymphomatous cells, cerebral lymphoma presents characteristic diffusion and
perfusion MRI features that should be useful for diagnosis and patient follow-up.
PMID- 17041527
TI - Reversible splenial lesion with restricted diffusion in a wide spectrum of
diseases and conditions.
AB - OBJECTIVE: Reversible lesion in the central area of the splenium of the corpus
callosum (SCC) is a unique phenomenon occurring particularly in patients with
encephalitis or encephalopathy and in patients receiving antiepileptic drugs
(AED). We report MR imaging findings, clinical courses, and outcomes in eight
patients with various diseases and conditions. MATERIALS AND METHODS: Eight
patients with a reversible SCC lesion with transiently restricted diffusion were
reviewed retrospectively. Diseases and conditions that were associated with a
reversible lesion included epilepsy receiving AED (n=1), seizure from eclampsia
receiving AED (n=1), mild infectious encephalitis (n=2), hypernatremia resulting
in osmotic myelinolysis (n=1), and neoplasm (n=3) such as acute lymphocytic
leukemia, spinal meningeal melanocytoma, and esophageal cancer. We evaluated MR
imaging findings and clinical findings. RESULTS: Seven patients had isolated SCC
lesions; one patient with osmotic myelinolysis showed additional parenchymal
lesions. The reversible SCC lesion shape was oval (n=6) or extended (n=2). The
mean apparent diffusion coefficient value of the splenial lesion was 0.40+/-0.16
x 10-3 mm2/s, ranging from 0.22 to 0.64 x 10-3 mm2/s. In a patient with osmotic
myelinolysis, additional white matter lesions, shown as restricted diffusion,
were revealed as not reversible on follow-up MR imaging. Neurological courses and
outcomes were good in seven patients with isolated SCC lesions, but poor in one
with osmotic myelinolysis. CONCLUSION: Reversible SCC lesion with restricted
diffusion is apparent in a wide spectrum of diseases and conditions. Neurological
courses and outcomes are good, particularly in patients with isolated SCC
lesions. Knowledge of MR imaging findings and the associated spectrum of diseases
and conditions might prevent unnecessary invasive examinations and treatments.
PMID- 17041528
TI - Facial malignant peripheral nerve sheath tumors.
AB - BACKGROUND/PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are rare
neoplasms, only sporadically reported involving the maxillo-mandibular region
(ten cases with CT or MR data). We present here five additional cases with CT and
MR findings along with an extensive review of the literature. RESULTS: Accurate
diagnosis of MPNSTs is difficult because pathological like radiological criteria
are often non specific. Radiological features display a large spectrum of
abnormalities from a well-delineated heterogeneous appearance simulating benign
schwannoma to extensive erosive patterns. Their development along the mandibular
nerve, the absence of any target or central dot sign, their strong predominant
peripheral enhancement must suggest the diagnosis of MPNSTs while irregular bone
destruction or the detection of poorly defined margins with muscular infiltration
are the most reliable criteria of malignancy. Unfortunately, MPNSTs also display
a considerably varied histology. Careful clinical and radiological correlation
should bring pathologists to examining large samples of the lesion to better
evaluate the overall organisation of the lesion and detect some evocative
criteria often only present in some areas of the sample as the peculiar curlicue
or whorled arrangement of the spindle cells or the alternation of densely
cellular fascicles with hypocellular, myxoid zones. Focal, limited immunostaining
for S-100 protein is one of the most important additional criterion. CONCLUSION:
If accurate early diagnosis often remains difficult, careful correlation of
clinical, pathological and radiological data should in most cases suggest a
diagnosis of MPNSTs which display a poor prognosis and requires early and adapted
treatment.
PMID- 17041529
TI - [MRI findings in neuro-Behcet's disease].
AB - PURPOSE: Describe the patterns and location of lesions seen on MR imaging in
neuro-Behcet's disease. OBSERVATIONS: 33 patients with neuro-Behcet's disease
(mean age: 27 years) imaged by MRI were reviewed. Most common neurologic symptoms
included headaches and pyramidal signs. MRI examinations (Siemens Magnetom Impact
1 Tesla) included the following sequences: T1wi, T2wi, Flair, MPR-3D and MRA
sequences. RESULTS: Parenchymal lesions were identified in 21 patients.
Brainstem, internal capsule, cerebral white matter, basal ganglia were involved
respectively in 14, 10, 7, and 5 cases. Vascular thrombosis (venous: n=7;
arterial: n=1) were observed in eight. MRI was normal in four patients.
CONCLUSION: This study shows the value of MR imaging for the exploration of
parenchymal lesions of neuro-Behcet's and confirms the frequency of brainstem
involvement.
PMID- 17041531
TI - Massive stroke in a patient with pituitary apoplexy, cervical carotid artery
stenosis and hypotension.
AB - We report a case of massive cerebral infarct in the early stage of pituitary
apoplexy. The case is unique because the stroke was delayed and occurred only
after the patient developed severe arterial hypotension superimposed on a tandem
internal carotid artery stenosis by both the sellar mass on the siphon and an
unknown homolateral atheromatous cervical lesion. Illustrated with MRI and
specifically by diffusion-weighted imaging, this case reinforces the idea that a
low apparent diffusion coefficient in a non-enhancing sellar mass may indicate
the presence of pituitary apoplexy and help in the early adequate management of
such patients.
PMID- 17041530
TI - Hyperselective intra-arterial preoperative chemotherapy in patients with squamous
cell carcinoma of the oral cavity: preliminary results.
AB - OBJECTIVES: To investigate radiological response and findings after Intra
Arterial Chemotherapy (IAC) for patients with Squamous Cell Carcinoma (SCC) of
the oral cavity. MATERIALS AND METHODS: Patients received 1-2 cycles of IAC.
Radiological assessment was performed on day 7 and day 21 after each cycle using
CT scan and MRI. RESULTS: Six patients (median age: 52, ranging 46-60;
male/female: 5/1) received 10 cycles (4 patients received 2 cycles). Primary
tumors were floor of the mouth (4 patients) and oral tongue (2 patients). TNM
classification was T2N0-2b in 3 patients and T4N0-1 in 3 patients. All patients
had good locoregional/systemic tolerance and 3 showed clinical objective response
(OR). Four patients were evaluable on both CT and MRI, 1 patient on MRI only and
1 patient did not tolerate imaging. Three patients showed OR both on CT and MRI,
1 patient showed stable disease (SD) on CT and OR on MRI and 1 patient showed SD
on MRI. Contrast-enhancement of hemiperfused tongue was reported in all evaluable
patients. Two patients presented intratumoral necrosis and 5 patients displayed
local edema (MRI). One patient had modification of the sternocleidomastoid muscle
after IAC. CONCLUSION: Radiological modifications were observed in the infused
area and correlated well with clinical response. This study is ongoing.
PMID- 17041532
TI - Bilateral wallerian degeneration of the middle cerebellar peduncles due to
unilateral pontine infarction.
AB - We report the case of a patient with bilateral and symmetrical T2
hyperintensities of the middle cerebellar peduncles. She had a history of left
pontine infarction 8 months before. This was attributed to bilateral Wallerian
degeneration. MR Spectroscopy showed decreased N-acetyl aspartate/Creatine
(NAA/Cr) ratio in the cerebellar peduncles as well as in the whole cerebellum. We
hypothesize that this could reflect neuronal degeneration following a stroke.
PMID- 17041533
TI - [Imaging follow-up of post-traumatic myelomalacia].
AB - The authors report a case of secondary worsening of neurological symptoms in a
patient 2 months after cord injury at T5 causing paraplegia. The MRI showed
myeolomalacia, which appears as cord oedema, located in the grey matter,
extending increasingly from the initial lesion (eighth thoracic vertebra) to the
bulb. This cord lesion known as grey matter cytotoxic oedema, evolved into a
syringomyelic cavity.
PMID- 17041534
TI - Intracerebral epidermoid tumor: pathogenesis of intraparenchymal location and
magnetic resonance imaging findings.
PMID- 17041535
TI - Malignant oculomotor schwannoma: diffusion MR imaging.
PMID- 17041536
TI - Endovascular treatment of ruptured intracranial aneurysms: immediate result and
long term follow up.
PMID- 17041537
TI - [Neurosarcoidosis as the initial presentation of systemic sarcoidosis].
PMID- 17041538
TI - The abnormally dilated internal auditory canal: a non-specific finding or a
distinctive pathologic entity.
PMID- 17041539
TI - Comparison of multidetector row CT cross-sectional source images with multiplanar
2D-, 3D- reconstructions and virtual endoscopy in assessment of the middle ear.
PMID- 17041540
TI - [Atypical location of a solitary fibrous tumor in the fourth ventricle].
PMID- 17041542
TI - Granular cells tumour in the oral cavity: report of eleven cases treated with
laser surgery.
AB - AIM: The aim of this paper is to examine the clinical and histological feature of
oral tumours of neural derivation and discuss their treatment. METHODS: Between
1999 and 2004, 11 patients (6 females, 5 males; age range 28-66 years) were
treated for tumours classified as being of neural origin; they were all
myoblastomas or granular cells tumours (ex Abrikossoff tumour). Eight were
located on the dorsum of the tongue, 2 on the lateral margin and 1 on the right
buccal mucosa. In all cases the mass appeared nodular, single and firm; patients
were treated in a single session by excisional resection with 808 and 830 diode
laser. RESULTS: During follow-up, which ranged from 5 months to 5 years, there
was no indication of tumour recurrence. Histopathological analysis of
haematoxylin and eosinstained sections showed all specimens to exhibit features
typical of GCT; 6 tumours were well circumscribed, whereas 5 infiltrated adjacent
connective tissue, muscle fibres and nerve bundles. In 10 of the 11 cases, the
immunohistochemical S-100 protein stain was available and appeared positive.
Pseudo-epitheliomatous hyperplasia of different degrees was present in 5
patients, along the overlying epithelium. CONCLUSIONS: Granular cell tumour is a
benign neoplasm with a tendency to relapse if not completely removed. The
usefulness of laser in the surgical treatment of these tumours particularly if
small in size, is underlined.
PMID- 17041541
TI - The condyle-fossa relationship in temporomandibular disorders. Considerations on
the pathogenetic role of the disc.
AB - AIM: The purpose of this study is to evaluate the condylar position and its
variation in patients with temporomandibular joint (TMJ) disorders before and
after therapy with occlusal gnathologic devices. METHODS: Twenty-five TMJ of 25
patients with temporomandibular joint disorder were examined by linear
measurement of the anterior, posterior and superior joint space between the
condyle and glenoid fossa through cephalometric analysis on X-ray tomography of
the TMJ and by calculating the condylar position with the Pullinger and Hollender
method. RESULTS: The average condylar position in the TMJ with DTM was posterior
with a mean value of 22.2% and a range from 14.3% to 36%. The condylar position
of 25 TMJs was: anterior 0(0%); centric 8(32%) and posterior 17(68%). After
therapy with occlusal gnathologic devices the average condylar position was
centric with a mean value of 0.6% and a range from 5.3% to 6.6%. The condylar
position of 25 TMJs was: anterior 2(8%); centric 22(88%) and posterior 1 (14%).
CONCLUSIONS: The hypothesis can be advanced that joint pathology is the
consequence of the alteration of the condyle position and therefore of the
mandibular movement and vice versa. Therapy with occlusal devices makes it
possible to modify the condylar position by increasing the condylar capability to
recapture the joint disc.
PMID- 17041543
TI - Clinical evaluation of an ointment with 10% metronidazole and 2% lidocaine in the
treatment of alveolitis.
AB - AIM: In this study, the authors evaluate the use of a 10% metronidazole and 2%
lidocaine ointment, using a lanolin base and mint as flavoring, to treat
alveolitis in humans. METHODS: Twenty-five patients, with a diagnosis of
alveolitis, were treated in the following way: locoregional anesthesia; surgical
cleaning of the socket with alveolar curettes; saline solution irrigation with a
20 ml disposable syringe; and complete filling of the socket with the ointment.
RESULTS: The analysis of the results showed that the painful symptoms were severe
before and on the day of the treatment in 17 (68%) of the 25 patients treated.
Post-treatment analysis presented 2 patients (18%) with severe painful symptoms
after 24 h of the treatment and complete remission of painful symptoms after 48 h
of the treatment with the ointment. CONCLUSIONS: Based on the results, it is
possible to conclude that the 10% metronidazole and 2% lidocaine ointment, with
mint flavoring and lanolin as a base, can be used to treat alveolitis.
PMID- 17041544
TI - Effectiveness of a glutaraldehyde formulation in decontamination of dental unit
water systems.
AB - AIM: Dental-medical devices may transmit infections caused by bacteria that are
usually found in water distribution systems, and which are difficult to treat and
control. High bacterial contamination in the water systems of dental units is due
to the presence of biofilm inside the pipes. Our study evaluated the efficacy of
glutaraldehyde formulated with quarternary ammonium salts (Sanicide T4) examined
in a previous study, employing a series of assays to confirm or otherwise the
results obtained previously. METHODS: A purification protocol for the dental unit
water system, together with a protocol for daily maintenance treatment, were
tested on two dental units (in the Departments of Conservative and Prosthetic
Dentistry) taking specimens from the turbine, micro-engine and air-water gun. The
chemical substance, at a concentration of 20 cc per litre of water, was allowed
to act when the department closed, for a total of 15 days. The Sanicide T4 was
handled with protective gloves and the dental units were fitted with two safety
devices to avoid accidental ingestion. RESULTS: Laboratory results enabled us to
compare values for bacterial load at 36 degrees C and at 22 degrees C and for
Pseudomonas aeruginosa, before and after applying the test protocol. Data
obtained are satisfactory except for Pseudo-monas in the fountain in the
Department of Conservative Dentistry; the value was in any case below the safety
level set by the American Dental Association, confirming the results obtained in
our previous study. CONCLUSIONS: The two protocols may now be considered an
excellent solution to control the development of biofilm. Should the product be
found to be effective for a longer period of use, each dental unit should be
provided with: an anti-reflux valve to stop accidental ingestion of disinfectant;
a hydraulic mechanism to pump the product to the handpieces and other water
supply devices; possibility of discriminating the use of the public water system
from the use of that in the disinfectant circuit; an automatic mechanism whereby
the disinfectant can be flushed out with drinking water every morning.
PMID- 17041545
TI - Caries-risk assessment: the role of salivary tests.
AB - Although the incidence of caries has diminished dramatically over the past 3
decades, small groups of subjects remain highly susceptible and do not respond to
conventional preventive programs. An accurate individual caries-risk assessment
allows to identify the etiological factors responsible for the disease and design
a rational approach to treatment, addressed to the specific needs of the
patients. The use of appropriate caries-risk prediction models, which include the
use of simple chairside caries-susceptibility salivary tests, is the most
suitable and modern approach to the problem. A review of the literature on
salivary tests, at present available, able to identify the factors contributing
to caries susceptibility, is presented. Each test is accurately described, with
regard both to its procedure and the interpretation of its results:
PMID- 17041546
TI - Facial nerve paralysis following mandibular trauma: a case report.
AB - A strong posteriorly directed force applied to the mandible resulting in
fracture, can also displace the mandibular condyle towards the external auditory
canal or superiorly against the mandibular fossa, causing its penetration into
the middle cranial fossa or even the fracture of the temporal bone. We report the
case of a 30-year-old male patient victim of a bicycle accident that developed
facial expression muscles paralysis on the left side soon after the trauma. On
physical examination he presented left side postauricular ecchymosis, diminished
muscular tonus of the left mouth angle and difficulty to close the left eye, he
did not present clinical signs of facial fractures. The neurological and CT scan
examination revealed fracture of the left temporal bone with total facial
expression muscles paralysis. The patient was referred to the neurosurgical team
for evaluation and they opted for a conservative treatment. After 3 months the
patient showed a marked improvement with almost normal facial expression muscle
movements. The trauma dynamics and treatment details are discussed.
PMID- 17041547
TI - A review of endoparasitic acarines of Malaysia with special reference to novel
endoparasitism of mites in amphibious sea snakes and supplementary notes on
ecology of chiggers.
AB - Some 2,000 species of mites of the family Trombiculidae are known in the world.
The 6-legged larvae are mostly ectoparasites of reptiles, birds, mammals and
invertebrates. Their 8-legged active nymphs and adults are free-living predators.
In the Asia-Pacific region, a few species in various genera are vectors of scrub
typhus and scrub-itch. In this a paper, a very bizarre trombiculid species,
Vatacarus ipoides Southcott 1957, endoparasitic in the trachea of the amphibious
sea snake, Laticauda colubrina (Schenider) is re-described based mostly on new
born larvae reared in the laboratory. Life history study of the mite produced
very novel and interesting results. A brief account of the life-cycle was
presented at the first laboratory demonstration of the Malaysian Society of
Parasitology and Tropical Medicine Meeting by Nadchatram and Audy (1965). The
life history is illustrated and described here in greater detail. The active
nymphal, and the akinetic teleiophane stages are bypassed, which is unusual in
the life-cycle of the family Trombiculidae. Also, the larva is the only stage in
the life-cycle that feeds. The sexes are predetermined in the larval neosomatic
stage and give rise to small males and bigger females. Having obtained adults of
the species, by rearing, it is deemed unnecessary for the original proposal by
Southcott to erect a new family, Vatacaridae, because the adults share all the
attributes of the family Trombiculidae. The male and female obtained through
laboratory rearing are illustrated for the first time. Relationship of V. ipoides
with Laticauda snakes show close host-specificity, in a group of acarines that
are generally habitat-specific. Possible explanations for their association are
discussed. The unusual morphology and the formation of new structures during an
instar is of ontogenetic and evolutionary importance. The hypertrophic larvae are
superficially vermiform, rather than typically acarine in shape. This, and other
biological features, necessitated the proposal of new morphological terms, and
they are discussed here.
PMID- 17041548
TI - Daily feeding of fresh Neem leaves (Azadirachta indica) for worm control in
sheep.
AB - This study was Conducted To Evaluate The Anthelmintic Effect Of Neem (azadirachta
Indica) On Nematode Parasites Of Sheep. Twelve Santa Ines Cross Bred Sheep From A
Government Farm were randomly selected and equally divided into control (n = 6)
and treated groups (n =6). Faecal egg counts (FEC) using the modified McMaster
technique and the FAMACHA score for assessing clinical anaemia were carried out
daily and recorded for 6 weeks. At the end of the study all the animals were
slaughtered and the total worm count (TWC) was done. The results of FEC showed
that there was no significant difference between the control and treated group (p
= 0.081). However, worm burden estimations showed that the number of parasites
was significantly higher in the control group compared to the treated group (p <
0.05). This result indicated that feeding Neem had an effect on worm numbers in
sheep, but was not reflected in their faecal egg counts. Further work is needed
to reconfirm the effect of Neem on helminth infections of sheep.
PMID- 17041549
TI - Use of molecular tools to distinguish Entamoeba histolytica and Entamoeba dispar
infection among the aborigines in Cameron Highlands.
AB - Amoebiasis is an infectious diseased caused by parasitic one-celled protozoan
called Entamoeba histolytica. Numerous protozoa also can inhabit the gastro
intestinal tract of human. Majority of these protozoa are non-pathogenic
commensals or only causes disease under certain circumstances. Morphologically,
E. histolytica, the invasive form, share the same characteristic with the
nonpathogenic form, E. dispar. Both strains can be distinguished by using DNA
identification. Many previous researches in Malaysia only reported infection with
E. histolytica infection. Therefore in this study we tried to classify infection
among the aborigines in Cameron Highland as true E. histolytica or E. dispar by
Nested Polymerase Chain Reaction (Nested PCR) and Restriction enzyme (RE)
digestion. Results showed that 31 samples were positive by microscopic
examination, however of these 28 (13.2%) samples were positive for E. histolytica
and 12 (5.6%) samples were positive for E. dispar by molecular tools.
PMID- 17041550
TI - Field evaluation of Bacillus thuringiensis H-14 against Aedes mosquitoes.
AB - Studies were carried out on the residual efficacy of Bacillus thuringiensis H-14
(water dispersible granule, VectoBac ABG 6511) as direct application in the
control of Aedes larvae in the field. Field Aedes sp populations in the earthen
and glass jars were predetermined before initiation of the trial. On confirmation
of the presence of Aedes species in the designated area, Sungai Nibong Kecil,
Penang Island, Malaysia, Bti was introduced in the 55L earthen and 3L glass
jars). Two test designs were carried out. The first design had treated water
replenished daily with 6L of seasoned water and the second design is without the
replenishment of water but evaporated water was replenished. Bti was effective in
the field for at least 35 days with more than 80% reduction in the Aedes larvae
in the treated containers. For earthen jars with daily replenishment of water,
100% reduction was recorded for the first 3 days, while more than 80% reduction
was recorded up to day 40. At day 60, Bti still provided an efficacy of 54.32 +/-
4.61 (%) of reduction. Whilst for earthen jars without daily replenishment of
water, 100% reduction was recorded for the first 5 days, while more than 80% of
reduction was recorded up to day 40. For the glass jars studied, similar efficacy
was observed. In jars with daily replenishment of water a better larval control
was observed. Percentage of reduction from day 50 to 60 for replenishment of
water was between 50 to 70% compared to without replenishment of water with less
than 40%.
PMID- 17041551
TI - Recovery of phosphatase and transaminase activity of mercury intoxicated Mus
musculus (Linn.) liver tissue by Tribulus terrestris (Linn.) (Zygophyllaceae)
extract.
AB - The efficacy of the methanolic fraction (MF) of Tribulus terrestris fruit extract
on mercury intoxicated mice, Mus musculus has been studied. At a median-lethal
dose of mercuric chloride (12.9 mg/kg body wt.) administration an enhanced level
of glutamate oxaloacete transaminase (GOT), glutamate pyruvate transminase (GPT)
and simultaneously decreased level of acid phosphatase (ACP) and alkaline
phosphatase (ALT) activities were noticed in the liver. Due to the mercury
toxicity the liver cells are damaged to cause the alterations in their enzymes.
During the recovery period, all the enzymological parameters are restored to
reach near normal level. The result suggested that the oral administration of MF
of T. terrestris fruit extract has (6 mg/kg body wt.) provided protection against
the mercuric chloride induced hepatic damage in the mice, M. musculus.
PMID- 17041552
TI - Quantitative analysis of the expression of p53 gene in colorectal carcinoma by
using real-time PCR.
AB - Colorectal carcinoma ranks third among ten leading causes of cancer in Malaysia.
The colorectal carcinoma tumourigenesis involves the inactivation of tumour
suppressor genes, and activation of proto-oncogenes. The p53 is one of the tumour
suppressor genes that is involved in the colorectal carcinogenesis. The p53 gene
is located on human chromosome 17p13.1 and comprises of 11 exons. Deficiencies in
the p53 gene can cause the cancerous cells to spread to distant organs such as
liver, lungs, lymph nodes, spine and bone. The most common p53 abnormalities that
can lead to the metastasis of colorectal tumours are mutation and deregulation of
the gene. In this study, nine colorectal carcinoma samples were used to establish
a simple and sensitive strategy in the study on in vivo p53 expression by using
realtime LightCycler SYBR Green I technology.
PMID- 17041553
TI - Condemnation of lungs in abattoirs in peninsular Malaysia due to parasitic
infection from 1998-2004.
AB - A study on causes of lung condemnation in 25 abattoirs from peninsular Malaysia
for a period of seven years (1998-2004) was conducted by examining the records at
the Department of Veterinary Services headquarters in Kuala Lumpur. A total of
5.3% of lungs from 233,417 cattle and buffaloes were condemned from 1998 to 2004.
The main cause of condemnation was congestion (2.98%). The percentage of lungs
that were condemned due to parasitic infection among the total population
slaughtered was low (0.11%). Parasitic infection contributed to 2.1% of all lungs
condemned. It was also found that the prevalence of parasitic infection in the
lungs was generally much higher in buffaloes than in cattle.
PMID- 17041554
TI - A transmission electron microscopy study on effects of a modified Glutaraldehyde
fixation on Acanthamoeba castellanii.
AB - Transmission electron microscopy (TEM) can provide high resolution imaging of
biological specimens. The study is to establish the effects of a modified
glutaraldehyde (GA) compare to the standard GA fixation on Acanthamoeba
castellanii from TEM perspectives and thus provide precise and accurate
information on the ultrastructure studies of the parasite. By increasing the
contrast, the ultrastructures of the parasite were more evident. The TEM images
were obtained from parasites fixed with the modified GA and the standard GA and
then the area of the nucleus and the gray values of the image of the nucleus of
the parasites were measured. The mean areas of the nucleus were found to be
significantly reduced in the standard GA fixed parasites (12210.4 nm2) compared
to the modified GA fixed parasites (8676.3 nm2) (p < 0.05). The mean gray values
of the image were significantly reduced from 2024 in the standard GA fixed
parasites (2024) to the modified GA fixed parasites (1636) (p < 0.05). The study
shows that the modified GA produced significantly better contrast on TEM images
of the A. castellanii compared to the standard GA. This was because the modified
GA generated more free water molecules during fixation and the uptake of modified
GA by the nucleus of the parasite organizing all protein constituents in the cell
into a more closely packed configuration than that of the standard GA. With such
properties, the modified GA is a better fixative providing better images for
ultrastructures of the parasite.
PMID- 17041555
TI - Prevalence and factors related to smoking among secondary school students in Kota
Tinggi District, Johor, Malaysia.
AB - Smoking among adolescent is a public health concern in Malaysia. Multiple studies
on smoking prevalence and its related factors have been conducted in Malaysia,
however, they were specific to either urban or rural areas alone. Studies in
mixed settlement areas (urban, rural, land development area) had not been
intensively investigated. This study reports the prevalence, demographic and
factors related to smoking amongst form four students in the district of Kota
Tinggi, Johor. A cross-sectional study of 16-year old secondary school students
in Kota Tinggi district was conducted using two-stage stratified, proportionate
sampling in July 2005. The study instrument used was a validated structured
questionnaire on smoking and its related factors. Smoking prevalence was found to
be 29.7%. More than 50% of male students were smokers. Prevalence was highest in
FELDA (Federal Land Development Authority) settlement areas. Smoking was
associated with having a brother or friend who smokes and poor academic
performance. The study revealed that smoking prevalence was high, especially
among male students in land development schemes. This situation will contribute
to high smoking-related health problems in the future if proper preventive
measures are not taken accordingly.
PMID- 17041556
TI - Spatial, environmental and entomological risk factors analysis on a rural dengue
outbreak in Lundu District in Sarawak, Malaysia.
AB - The objective of this study was to elucidate the association of various risk
factors with dengue cases reported in Lundu district, Sarawak, by analyzing the
interaction between environmental, entomological, socio-demographic factors.
Besides conventional entomological, serological and house surveys, this study
also used GIS technology to generate geographic and environmental data on Aedes
albopictus and dengue transmission. Seven villages were chosen based on the high
number of dengue cases reported. A total of 551 households were surveyed. An
overall description of the socio-demographic background and basic facilities was
presented together with entomological and geographical profiles. For serological
and ovitrap studies, systematic random sampling was used. Serological tests
indicated that 23.7% of the 215 samples had a history of dengue, either recent or
previous infections. Two samples (0.9%) were confirmed by IgM ELISA and 49
samples (22.8%) had IgG responses. A total of 32,838 Aedes albopictus eggs were
collected in 56 days of trapping. Cluster sampling was also done to determine
whether any of the risk factors (entomological or geographical) were influenced
by geographical location. These clusters were defined as border villages with
East Kalimantan and roadside villages along Lundu/Biawas trunk road. The data
collected were analyzed using SPSS version 10.01. Descriptive analysis using
frequency, means, and median were used. To determine the association between
variables and dengue cases reported, and to describe the differences between the
two clusters of villages, two-sample t-test, and Pearson's Chi-Square were used.
Accurate maps were produced with overlay and density function, which facilitates
the map visualization and report generating phases. This study also highlights
the use of differential Global Positioning System in mapping sites of 1m
accuracy. Analysis of the data revealed there are significant differences in
clusters of villages attributable to container density, house density, distance
of the house from the main road, and number of Ae. albopictus eggs from ovitraps
set indoor, outdoor and in dumping sites (Person's Chi-Square = 6.111, df = 1, p
< 0.01). Further analysis using t-test showed that house density, container
density, indoor mosquitoes egg count, outdoor mosquitoes egg count, and dumping
sites mosquitoes egg count were higher at the roadside villages compared to
border villages. A number of potential risk factors including those generated
from GIS were investigated. None of the factors investigated in this study were
associated with the dengue cases reported.
PMID- 17041557
TI - Detection of insecticides resistance status in Culex quinquefasciatus and Aedes
aegypti to four major groups of insecticides.
AB - The resistance to various insecticides from 4 major groups (organochlorine,
organophosphate, carbamate and pyrethroid) was investigated in a field strain of
Culex quinquefasciatus from Baan Suan community, Nonthaburi province, Thailand by
using a standard World Health Organization susceptibility test. The Baan Suan
strain was completely resistant to DDT and highly resistant to deltamethrin,
permethrin, fenitrothion and propoxur but this strain was still found to be
highly susceptible to malathion. This strain displayed high resistance to
cypermethrin since the result revealed that the resistance ratio of the 50%
lethal concentration value (RR50) between the field and the laboratory strains
(NIH strain) was 16. The study indicated that mosquitoes were resistant to almost
all insecticide tested except malathion and this should be an alternative for Cx.
quinquefasciatus control in this area. Moreover, Aedes aegypti, which is a main
dengue vector in Baan Suan community was also tested with deltamethrin,
permethrin and fenitrothion. The results showed that dengue mosquitoes are
clearly resistant to permethrin and tolerant to deltamethrin, but was 100%
susceptible to fenitrothion. The cause of insecticide resistance in Cx.
quinquefasciatus may be due to the continuous use of insecticide for dengue
vector control programme in Baan Suan community.
PMID- 17041558
TI - Some epidemiological aspects of intestinal parasites in women workers before
going abroad.
AB - A study was conducted in Jakarta on 903 women workers before going abroad through
stool examination by Ritchie's technical method. Of the women workers studied,
640 subjects (70.87%) were found to be infected with intestinal parasites either
helminthes, protozoa or combination. Out of those infected, 451 (70.47%) subjects
were infected with intestinal helminthes, namely Ascaris lumbricoides (38.13%),
Trichuris trichiura (28.13%), a combination of Necator americanus and Ancylostoma
duodenale (13.59%) and Enterobius vermicularis (4.84%). In addition 319 (49.84%)
subjects were infected with intestinal protozoa namely Giardia lamblia (22.03%),
Entamoeba histolytica (14.53%), Blastocystis hominis (6.56%) and Entamoeba coli
(6.72%). The youngest age to be affected was 14 years old (14.19% of the subjects
studied). Majority (72.09%) of the study subjects received junior high school
level of education. Home yard (46.51%) and ground under the trees (22.09%) were
places favourable for the habits of defaecation, whereas garbage disposal took
place in 52.33% home yards and 25.58% creeks. This study revealed that various
life style habits and indiscriminate defaecation were the causes of the
continuous transmission of intestinal parasitic infections. The different
parasites that were found in women workers before going abroad relate to the
various epidemiological aspects of intestinal parasites in women workers in
Indonesia who came from different islands in the country and possessed different
life style patterns, socioeconomic status, geographical condition and cultures.
PMID- 17041559
TI - A cost-effective modified micromethod for measuring urine iodine.
AB - A modified micromethod for measuring urine iodine was successfully established
and validated. The micromethod showed good correlation with the method used by
several World Health Organization (WHO) collaborative laboratories (y = 0.9342x +
4.6213; r = 0.962; p = 0.01; n = 50). The micromethod also showed good agreement
when compared to the reference WHO method. The sensitivity of the assay was
13.809 ug/L (n = 8) and mean recoveries were 114, 103 and 106% at concentrations
of 30, 40 and 50 ug/L (n = 3) respectively. At iodine concentrations of 51 +/-
15.5, 108 +/- 32.4 and 149 +/- 38.6 ug/L, intra-assay coefficient of variations
(CVs) were 13%, 7% and 5% respectively (n = 20), and inter-assay CVs were 10%,
15% and 7% respectively (n = 10). The assay showed good linearity plot (y =
1.0407x + 60.451; r = 0.993; n = 3).
PMID- 17041560
TI - Infection of Blastocystis hominis in primary schoolchildren from Nakhon Pathom
province, Thailand.
AB - A study was conducted to evaluate the infection status of Blastocystis hominis in
children from four public schools in Phuttamonthon district, Nakhon Pathom
province, Thailand during November to December 2004. A total of 814 faecal
specimens were used for B. hominis cultivation using Jones' medium. Mixed
infections with other intestinal parasites were also examined by formalin ethyl
acetate concentration method. It was found that 13.51% (110 of 814) of the
children examined were infected with B. hominis. Mixed infections with other
intestinal protozoa and helminths were observed in 10.91% (12 of 110) of B.
hominis positive specimens. There were Giardia lamblia cysts (4.55%), Trichomonas
hominis trophozoites (1.82%), Entamoeba histolytica cysts (0.91%), Endolimax nana
cysts (0.91%), Strongyloides stercoralis larvae (0.91%), hookworm eggs (0.91%),
and Trichuris trichiura eggs (0.91%). Of the children positive for B. hominis,
there was no significant differences between sex (P > 0.05) and showed no
correlation between age and the percentage of infection. The different infection
rates among four schools indicated the involvement of hygienic factors which
promoted the infection of this common intestinal protozoan. Variation in size of
B. hominis was found in culture medium, which might indicate to the presence of
different strains of B. hominis infection.
PMID- 17041561
TI - The application of PCR-ELISA to the detection of Trypanosoma congolense type
savannah (TCS) in bovine blood samples.
AB - PCR-ELISA was set up to detect strains of Trypanosoma congolense type savannah
(TCS) in field samples of buffy coats. Results of PCR-ELISA and PCR were compared
and the effectiveness of both techniques was also compared with the Murray's
method for the detection of TCS in 257 bovine buffy coats. The PCR products were
labelled with digoxigenin (DIG-dUTP) during amplification cycles of the
repetitive satellite DNA. A biotinylated DNA capture probe was used to detect the
PCR products by ELISA in streptavidin coated microplates. Both the PCR-ELISA and
PCR were more sensitive and more specific than the Murray's method. Of the 257
buffy coats analysed by the three techniques, PCR-ELISA and PCR detected TCS in
98 and 97 buffy coats respectively, whereas the Murray's method detected only 39
samples. PCR-ELISA and PCR had almost the same sensitivity and specificity. PCR
ELISA and PCR respectively detected TCS in 39.2% and 38.6% in all the 334 samples
analysed by both techniques in this study.
PMID- 17041562
TI - Notes on some ectoparasites received by the Medical Entomology Unit, Institute
for Medical Research.
AB - There were a spate of recent complaints of insect bites and the entomological
specimens received from various sources were identified to be those of cat flea
(Ctenocephalides felis) and rat flea (Xenopsylla cheopis), the tropical bed-bug
(Cimex hemipterus) and the dog louse (Heterodoxus spiniger). Only the fleas and
the bed-bug are known to attack humans.
PMID- 17041564
TI - Antisense and nonantisense effects of antisense Bcl-2 on multiple roles of Bcl-2
as a chemosensitizer in cancer therapy.
AB - Bcl-2 is an oncoprotein that plays a critical role in inhibiting apoptotic cell
death in the mitochondria-dependent pathway in cancer chemotherapy. As a strategy
for blocking Bcl-2 for enhancement of the chemotherapeutic effect, antisense Bcl
2 (AS Bcl-2; G3139, oblimersen sodium, Genasense) has shown promise, and there
are several ongoing clinical studies with hematological malignancies as well as
solid tumors. Although several preclinical and clinical studies have shown the
therapeutic efficacy of Bcl-2 in combination with an anticancer drug as a
chemosensitizer, in clinical trials the downregulation of Bcl-2 has not been
observed with a high frequency in tumor cells. Nevertheless, previous studies
showed nonantisense effects such as production of reactive oxygen species and
immunostimulatory action through cytosine-phosphate-guanosine-motif in the
antisense oligodeoxynucleotides. Further, Bcl-2 is able to inhibit Beclin 1
dependent autophagic cell death, which is a nonapoptotic cell death. The current
status and future directions of AS Bcl-2 and the potential mechanisms for
multiple roles that Bcl-2 has in cancer therapy are reviewed.
PMID- 17041563
TI - International Society for Cell and Gene Therapy of Cancer: 2005 meeting in
Shenzhen, China.
AB - The 2005 International Society for Cell and Gene Therapy of Cancer (ISCGT)
Congress was held in Shenzhen, China (www.iscgtchina2005.com) from December 9th
11th 2005. Here, we describe a representation of the most seminal presentations
providing an overview of the progress in the field of cancer gene therapy
including the successful introduction of the first approved gene therapy drug.
PMID- 17041565
TI - Intramucosal gastric adenocarcinoma of poorly differentiated type in the young is
characterized by Helicobacter pylori infection and antral lymphoid hyperplasia.
AB - The aim of this investigation was to clarify the histological characteristics of
gastric cancer in the young. Twenty-three surgically resected specimens of young
patients (under 30 years of age; young group) with intramucosal cancer of poorly
differentiated type and 42 surgically resected specimens of elderly patients
(more than 40 years of age; elderly group) with tumors of the identical depth and
histological type were examined. The degree of gastritis and Helicobacter pylori
(H. pylori) infection was evaluated according to the updated Sydney system. The
incidence of H. pylori infection was significantly higher in the young group than
in the elderly group (96 vs 36%, P<0.05). Within the background mucosa, antral
chronic inflammatory infiltrates with lymphoid-follicle hyperplasia were more
severe, and intestinal metaplasia was less frequent in the young group than in
the elderly group. Glandular atrophy was not different between the two groups.
Intramucosal gastric adenocarcinomas of poorly differentiated type in the young
may be associated with H. pylori infection with antral chronic inflammation with
lymphoid-follicle hyperplasia, regardless of the existence of intestinal
metaplasia within the background gastric mucosa.
PMID- 17041566
TI - Heparanase upregulation by colonic epithelium in inflammatory bowel disease.
AB - Heparanase is an endo-beta-D-glucuronidase capable of cleaving heparan sulfate
(HS) side chains at a limited number of sites, yielding HS fragments of still
appreciable size ( approximately 5-7 kDa). Heparanase activity has long been
detected in a number of cell types and tissues. Importantly, heparanase activity
correlated with the metastatic potential of tumor-derived cells, attributed to
enhanced cell dissemination as a consequence of HS cleavage and remodeling of the
extracellular matrix barrier. Similarly, heparanase activity was implicated in
neovascularization, inflammation and autoimmunity, involving migration of
vascular endothelial cells and activated cells of the immune system. The
involvement of heparanase in inflammatory processes of the gastrointestinal tract
has not been examined. Here, we utilized immunohistochemical analysis to
investigate heparanase expression in acute and chronic inflammatory conditions.
Heparanase expression was not detected in specimens derived from normal colon
tissue. In contrast, strong heparanase staining was observed in Crohn's disease
and ulcerative colitis, but not in infectious colitis. Interestingly, heparanase
staining was primarily observed in epithelial rather than immune cells.
Importantly, un-fractionated as well as low molecular weight heparin
(enoxaparin), which exhibit a strong inhibitory activity towards heparanase, have
proven efficacious in ulcerative colitis and Crohn's disease patients, suggesting
that heparanase is actively involved in these pathologies and thus may be
considered as a target for the development of anti-inflammatory therapies.
PMID- 17041567
TI - Chronic myelomonocytic leukemia: The role of bone marrow biopsy immunohistology.
AB - The World Health Organization criteria for diagnosing chronic myelomonocytic
leukemia (CMML) are largely based on findings observed in the peripheral blood
and bone marrow aspirate. A specific diagnostic role for the bone marrow biopsy
has not been adequately explored. We examined whether bone marrow biopsy
supplemented by immunohistochemistry may be helpful in distinguishing CMML from
cases of chronic myelogenous leukemia and atypical chronic myeloid leukemia
(aCML). We immunostained 25 cases of CMML with paraffin reactive antibodies which
included CD68 (KP1), CD68R (PG-M1), and CD163, and compared the results with
those observed in six cases of chronic myelogenous leukemia and in three cases of
atypical CML. In addition, we examined whether CD34 immunohistochemistry could be
useful in separating cases of CMML with less than 10% blasts (type-1) from cases
of CMML with blasts accounting for 10-19% (type-2), and cases of CMML in acute
transformation to acute myeloid leukemia (blasts > or = 20%). The presence of
nodules of plasmacytoid monocytes was investigated by CD123 staining. CD42b was
used to highlight abnormal megakaryocytes. Our results demonstrate significant
differences between the groups. CD34 analysis allowed separating CMML type-1 from
type-2 and the former from CMML in acute transformation. CD123-positive
plasmacytoid monocyte nodules were found only in CMML and not in the other two
disease groups. Overlap between CMML and the other two groups were observed with
CD68 immunostaining. CD68R was more restricted to bone marrow macrophages and
monocytes than CD68, but the differences between CMML and chronic myelogenous
leukemia or atypical CML were still not significant. Although CD42b
immunostaining facilitated the detection of dwarf megakaryocytes often present in
CMML, the distinction between those and the small forms seen in chronic
myelogenous leukemia was still problematic.
PMID- 17041568
TI - Patient pathways for macular disease: what will the new optometrist with special
interest achieve?
PMID- 17041570
TI - Retinal detachment following meningococcal endophthalmitis.
PMID- 17041572
TI - Locking the Luer lock.
PMID- 17041573
TI - Ciliary body naevus.
AB - PURPOSE: To describe clinical, ultrasound biomicroscopy (UBM), and
histopathologic characteristics of benign melanocytic tumors of the ciliary body.
DESIGN: Consecutive case series. METHODS: Six patients with a pigmented ciliary
body tumour underwent complete ophthalmic examination and UBM, with
histopathologic examination carried out on three cases. RESULTS: Six patients
presented with a pigmented iridociliary mass, with central displacement of iris
root. UBM revealed a stromal mass arising in pars plicata and/or pars plana in
all six with a cyst in three cases (intrinsic=1 and extrinsic=2). Iridocyclectomy
was performed because of documented growth in three cases, and all three cases
proved to be ciliary body spindle-cell naevus. The other three patients have
remained stable. CONCLUSIONS: On clinical basis and with available ancillary
studies, ciliary body naevi cannot be reliably differentiated from ciliary body
melanocytoma and ciliary body melanoma. Even with clinically documented growth,
the lesions may prove to be ciliary body naevi.
PMID- 17041574
TI - Epileptic convulsion following aspirin withdrawal before lid surgery.
PMID- 17041575
TI - Pathological findings in the lens capsules and intraocular lens in chronic
pseudophakic endophthalmitis: an electron microscopy study.
AB - PURPOSE: The aim of this study was to describe the pathological findings in lens
capsules and intraocular lens (IOL) studied by scanning and/or transmission
electron microscopy (SEM and TEM, respectively) in a series of four eyes with
chronic pseudophakic endophthalmitis (CPE). PATIENTS AND METHODS: We performed a
retrospective study of four patients presenting CPE in whom surgical treatment
with pars plana vitrectomy, capsulectomy with extraction of the IOL, and
intravitreous antibiotic therapy was thereafter performed. The extracted IOL and
the capsular remains were studied by SEM and/or TEM and microbiologic analysis of
aqueous humour and vitreous aspirate was also carried out in all the cases.
RESULTS: The presence of microorganisms was observed in the material analysed in
all the cases studied. The use of TEM identified bacterial contamination by
Staphylococcus spp and mixed contamination with microorganisms presenting a
bacillar morphology suggestive of infection by Propionibacterium acnes in
addition to the presence of cocci in the capsular remains. In another two cases,
SEM localized colonies of Staphylococcus spp on the surface of the IOL in one
case and mixed bacterial colonization with cocci plus filamentous bacteria in the
other. The presence of macrophages associated with bacteria was observed in the
capsular remains. CONCLUSIONS: Microorganisms were found in the IOL or the
capsular material in the four cases studied, thereby explaining the
refractoriness and severity of infection. The possible presence of polymicrobial
infections, especially in the cases with filamentous bacteria, also explains the
recurrence of infection.
PMID- 17041576
TI - Phenotype of autosomal dominant cone-rod dystrophy due to the R838C mutation of
the GUCY2D gene encoding retinal guanylate cyclase-1.
AB - AIMS: To describe the phenotype of members of a large Caucasian British family
affected by autosomal dominant cone-rod dystrophy due to an R838C mutation in the
guanylate cyclase 2D (GUCY2D) gene encoding retinal guanylate cyclase-1 (RETGC
1). METHODS: Retrospective review of 29 patients from four generations of the
same family. RESULTS: Visual symptoms usually commenced in childhood. Only two
patients, aged 14 and 25 years, had visual acuity compatible with driving. Of the
12 patients aged over 40 years, eight (66%) had vision of counting fingers or
worse and were eligible for blind registration in the UK. Of the 29 patients, 18
(62%) had myopia greater than 5 D in at least one eye. Most had discernible
macular changes on biomicroscopy, which varied from subtle RPE change to gross
macular atrophy. All patients who underwent computerised perimetry exhibited a
central or paracentral scotoma with normal peripheral field of vision. Of the 21
patients who underwent electrodiagnostic testing, all exhibited decreased cone
function, but rod function was normal in 12 (57%) patients. CONCLUSION: We
believe this report highlights the importance of phenotype-genotype correlation
in cone and cone-rod dystrophies. Increased understanding of the varying
phenotypes associated with different genetic mutations allows appropriate
counselling of patients. In addition, the phenotypic characterisation of the
natural history of these conditions may prove valuable in the future should
therapeutic interventions become available.
PMID- 17041577
TI - Minimising blinding complications of cyclodiode laser in high risk and only eyes.
PMID- 17041578
TI - Use of 18-gauge intravenous catheter needle for frontalis suspension in children
with congenital ptosis.
PMID- 17041579
TI - Screening for wet AMD by optometrists: resistance to change or professional
rivalry?
PMID- 17041581
TI - Making metallic glasses plastic by control of residual stress.
AB - Metallic glasses, now that many compositions can be made in bulk, are of interest
for structural applications exploiting their yield stress and yield strain, which
are exceptionally high for metallic materials. Their applicability is limited by
their near-zero tensile ductility resulting from work-softening and shear
localization. Even though metallic glasses can show extensive local plasticity,
macroscopically they can effectively be brittle, and much current research is
directed at improving their general plasticity. In conventional engineering
materials as diverse as silicate glasses and metallic alloys, we can improve
mechanical properties by the controlled introduction of compressive surface
stresses. Here we demonstrate that we can controllably induce such residual
stresses in a bulk metallic glass, and that they improve the mechanical
performance, in particular the plasticity, but that the mechanisms underlying the
improvements are distinct from those operating in conventional materials.
PMID- 17041582
TI - Phase inversion of particle-stabilized materials from foams to dry water.
AB - Small particles attached to liquid surfaces arise in many products and processes,
including crude-oil emulsions and food foams and in flotation, and there is a
revival of interest in studying their behaviour. Colloidal particles of suitable
wettability adsorb strongly to liquid-liquid and liquid-vapour interfaces, and
can be sole stabilizers of emulsions and foams, respectively. New materials,
including colloidosomes, anisotropic particles and porous solids, have been
prepared by assembling particles at such interfaces. Phase inversion of particle
stabilized emulsions from oil in water to water in oil can be achieved either by
variation of the particle hydrophobicity (transitional) or by variation of the
oil/water ratio (catastrophic). Here we describe the phase inversion of particle
stabilized air-water systems, from air-in-water foams to water-in-air powders and
vice versa. This inversion can be driven either by a progressive change in silica
particle hydrophobicity at constant air/water ratio or by changing the air/water
ratio at fixed particle wettability, and has not been observed in the
corresponding systems stabilized by surfactants. The simplicity of the work is
that this novel inversion is achieved in a single system. The resultant materials
in which either air or water become encapsulated have potential applications in
the food, pharmaceutical and cosmetics industries.
PMID- 17041583
TI - High-performance transparent inorganic-organic hybrid thin-film n-type
transistors.
AB - High-performance thin-film transistors (TFTs) that can be fabricated at low
temperature and are mechanically flexible, optically transparent and compatible
with diverse substrate materials are of great current interest. To function at
low biases to minimize power consumption, such devices must also contain a high
mobility semiconductor and/or a high-capacitance gate dielectric. Here we report
transparent inorganic-organic hybrid n-type TFTs fabricated at room temperature
by combining In2O3 thin films grown by ion-assisted deposition, with nanoscale
organic dielectrics self-assembled in a solution-phase process. Such TFTs combine
the advantages of a high-mobility transparent inorganic semiconductor with an
ultrathin high-capacitance/low-leakage organic gate dielectric. The resulting,
completely transparent TFTs exhibit excellent operating characteristics near 1.0
V with large field-effect mobilities of >120 cm2 V(-1) s(-1), drain-source
current on/off modulation ratio (I(on)/I(off)) approximately 10(5), near-zero
threshold voltages and sub-threshold gate voltage swings of 90 mV per decade. The
results suggest new strategies for achieving 'invisible' optoelectronics.
PMID- 17041584
TI - Effects of hydration on molecular junction transport.
AB - The study of charge transport through increasingly complex small molecules will
benefit from a detailed understanding of how contaminants from the environment
affect molecular conduction. This should provide a clearer picture of the
electronic characteristics of molecules by eliminating interference from adsorbed
species. Here we use magnetically assembled microsphere junctions incorporating
thiol monolayers to provide insight into changing electron transport
characteristics resulting from exposure to air. Using this technique, current
voltage analysis and inelastic electron tunnelling spectroscopy (IETS)
demonstrate that the primary interaction affecting molecular conduction is rapid
hydration at the gold-sulphur contacts. We use IETS to present evidence for
changing mechanisms of charge transport as a result of this interaction. The
detrimental effects on molecular conduction discussed here are important for
understanding electron transport through gold-thiol molecular junctions once
exposed to atmospheric conditions.
PMID- 17041585
TI - Computational high-throughput screening of electrocatalytic materials for
hydrogen evolution.
AB - The pace of materials discovery for heterogeneous catalysts and electrocatalysts
could, in principle, be accelerated by the development of efficient computational
screening methods. This would require an integrated approach, where the catalytic
activity and stability of new materials are evaluated and where predictions are
benchmarked by careful synthesis and experimental tests. In this contribution, we
present a density functional theory-based, high-throughput screening scheme that
successfully uses these strategies to identify a new electrocatalyst for the
hydrogen evolution reaction (HER). The activity of over 700 binary surface alloys
is evaluated theoretically; the stability of each alloy in electrochemical
environments is also estimated. BiPt is found to have a predicted activity
comparable to, or even better than, pure Pt, the archetypical HER catalyst. This
alloy is synthesized and tested experimentally and shows improved HER performance
compared with pure Pt, in agreement with the computational screening results.
PMID- 17041586
TI - Gbetagammas and the Ras binding domain of p110gamma are both important regulators
of PI(3)Kgamma signalling in neutrophils.
AB - Through their ability to regulate production of the key lipid messenger
PtdIns(3,4,5)P(3), the class I phosphatidylinositol-3-OH kinases (PI(3)Ks)
support many critical cell responses. They, in turn, can be regulated by cell
surface receptors through signals acting on either their adaptor subunits (for
example, through phosphotyrosine or Gbetagammas) or their catalytic subunits (for
example, through GTP-Ras). The relative significance of these controlling inputs
is undefined in vivo. Here, we have studied the roles of Gbetagammas, the adaptor
p101, Ras and the Ras binding domain (RBD) in the control of the class I PI(3)K,
PI(3)Kgamma, in mouse neutrophils. Loss of p101 leads to major reductions in the
accumulation of PtdIns(3,4,5)P(3), activation of protein kinase B (PKB) and in
migration towards G-protein activating ligands in vitro, and to an aseptically
inflamed peritoneum in vivo. Loss of sensitivity of PI(3)Kgamma to Ras
unexpectedly caused similar reductions, but additionally caused a substantial
loss in production of reactive oxygen species (ROS). We conclude that
Gbetagammas, p101 and the Ras-RBD interaction all have important roles in the
regulation of PI(3)Kgamma in vivo and that they can simultaneously, but
differentially, control distinct PI(3)Kgamma effectors.
PMID- 17041587
TI - Input from Ras is required for maximal PI(3)K signalling in Drosophila.
AB - Class I phosphoinositide 3-kinases (PI(3)Ks) are activated through associated
adaptor molecules in response to G protein-coupled and tyrosine kinase receptor
signalling. They contain Ras-binding domains (RBDs) and can also be activated
through direct association with active GTP-bound Ras. The ability of Ras to
activate PI(3)K has been established in vitro and by overexpression analysis, but
its relevance for normal PI(3)K function in vivo is unknown. The Drosophila class
I PI(3)K, Dp110, is activated by nutrient-responsive insulin signalling and
modulates growth, oogenesis and metabolism. To investigate the importance of Ras
mediated PI(3)K activation for normal PI(3)K function, we replaced Dp110 with
Dp110(RBD), which is unable to bind to Ras but otherwise biochemically normal. We
found that Ras-mediated Dp110 regulation is dispensable for viability. However,
egg production, which requires large amounts of growth, is dramatically lowered
in Dp110(RBD) flies. Furthermore, insulin cannot maximally activate PI(3)K
signalling in Dp110(RBD) imaginal discs and Dp110(RBD) flies are small. Thus,
Dp110 integrates inputs from its phosphotyrosine-binding adaptor and Ras to
achieve maximal PI(3)K signalling in specific biological situations.
PMID- 17041588
TI - CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and
regulates histone methylation.
AB - The CUL4-DDB1-ROC1 ubiquitin E3 ligase regulates cell-cycle progression,
replication and DNA damage response. However, the substrate-specific adaptors of
this ligase remain uncharacterized. Here, we show that CUL4-DDB1 complexes
interact with multiple WD40-repeat proteins (WDRs) including TLE1-3, WDR5, L2DTL
(also known as CDT2) and the Polycomb-group protein EED (also known as ESC). WDR5
and EED are core components of histone methylation complexes that are essential
for histone H3 methylation and epigenetic control at K4 or K9 and K27,
respectively, whereas L2DTL regulates CDT1 proteolysis after DNA damage through
CUL4-DDB1 (ref. 8). We found that CUL4A-DDB1 interacts with H3 methylated
mononucleosomes and peptides. Inactivation of either CUL4 or DDB1 impairs these
histone modifications. However, loss of WDR5 specifically affects histone H3
methylation at K4 but not CDT1 degradation, whereas inactivation of L2DTL
prevents CDT1 degradation but not histone methylation. Our studies suggest that
CUL4-DDB1 ligases use WDR proteins as molecular adaptors for substrate
recognition, and modulate multiple biological processes through ubiquitin
dependent proteolysis.
PMID- 17041589
TI - TRAPPII subunits are required for the specificity switch of a Ypt-Rab GEF.
AB - Ypt-Rab GTPases are key regulators of the various steps of intracellular
trafficking. Guanine nucleotide-exchange factors (GEFs) regulate the conversion
of Ypt-Rabs to the GTP-bound state, in which they interact with effectors that
mediate all the known aspects of vesicular transport. An interesting possibility
is that Ypt-Rabs coordinate separate steps of the transport pathways. The
conserved modular complex TRAPP is a GEF for the Golgi gatekeepers Ypt1 and
Ypt31/32 (Refs 5-7). However, it is not known how Golgi entry and exit are
coordinated. TRAPP comes in two configurations: the seven-subunit TRAPPI is
required for endoplasmic reticulum-to-Golgi transport, whereas the ten-subunit
TRAPPII functions in late Golgi. The two essential TRAPPII-specific subunits
Trs120 and Trs130 have been identified as Ypt31/32 genetic interactors. Here, we
show that they are required for switching the GEF specificity of TRAPP from Ypt1
to Ypt31. Moreover, a trs130ts mutation confers opposite effects on the
intracellular localization of these GTPases. We suggest that the Trs120-Trs130
subcomplex joins TRAPP in the late Golgi to switch its GEF activity from Ypt1 to
Ypt31/32. Such a 'switchable' GEF could ensure sequential activation of these
Ypts, thereby coordinating Golgi entry and exit.
PMID- 17041590
TI - Electrostatic couplings in OmpA ion-channel gating suggest a mechanism for pore
opening.
AB - The molecular forces that drive structural transitions between the open and
closed states of channels and transporters are not well understood. The gate of
the OmpA channel is formed by the central Glu52-Arg138 salt bridge, which can
open to form alternate ion pairs with Lys82 and Glu128. To gain deeper insight
into the channel-opening mechanism, we measured interaction energies between the
relevant side chains by double-mutant cycle analysis and correlated these with
the channel activities of corresponding point mutants. The closed central salt
bridge has a strong interaction energy of -5.6 kcal mol(-1), which can be broken
by forming the open-state salt bridge Glu52-Lys82 (DeltaDeltaG(Inter) = -3.5 kcal
mol(-1)) and a weak interaction between Arg138 and Glu128 (DeltaDeltaG(Inter) =
0.6 kcal mol(-1)). A covalent disulfide bond in place of the central salt bridge
completely blocks the channel. Growth assays indicate that this gating mechanism
could physiologically contribute to the osmoprotection of Escherichia coli cells
from environmental stress.
PMID- 17041591
TI - Memory modulates color appearance.
AB - We asked human observers to adjust the color of natural fruit objects until they
appeared achromatic. The objects were generally perceived to be gray when their
color was shifted away from the observers' gray point in a direction opposite to
the typical color of the fruit. These results show that color sensations are not
determined by the incoming sensory data alone, but are significantly modulated by
high-level visual memory.
PMID- 17041592
TI - Activation of a presynaptic glutamate transporter regulates synaptic transmission
through electrical signaling.
AB - Whereas glutamate transporters in glial cells and postsynaptic neurons contribute
significantly to re-uptake of synaptically released transmitter, the functional
role of presynaptic glutamate transporters is poorly understood. Here, we used
electrophysiological recording to examine the functional properties of a
presynaptic glutamate transporter in rat retinal rod bipolar cells and its role
in regulating glutamatergic synaptic transmission between rod bipolar cells and
amacrine cells. Release of glutamate activated the presynaptic transporter with a
time course that suggested a perisynaptic localization. The transporter was also
activated by spillover of glutamate from neighboring rod bipolar cells. By
recording from pairs of rod bipolar cells and AII amacrine cells, we demonstrate
that activation of the transporter-associated anion current hyperpolarizes the
presynaptic terminal and thereby inhibits synaptic transmission by suppressing
transmitter release. Given the evidence for presynaptic glutamate transporters,
similar mechanisms could be of general importance for transmission in the nervous
system.
PMID- 17041593
TI - 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic
regulation of chromatin structure.
AB - Temporal lobe epilepsy is a common form of drug-resistant epilepsy that sometimes
responds to dietary manipulation such as the 'ketogenic diet'. Here we have
investigated the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in
the rat kindling model of temporal lobe epilepsy. We show that 2DG potently
reduces the progression of kindling and blocks seizure-induced increases in the
expression of brain-derived neurotrophic factor and its receptor, TrkB. This
reduced expression is mediated by the transcription factor NRSF, which recruits
the NADH-binding co-repressor CtBP to generate a repressive chromatin environment
around the BDNF promoter. Our results show that 2DG has anticonvulsant and
antiepileptic properties, suggesting that anti-glycolytic compounds may represent
a new class of drugs for treating epilepsy. The metabolic regulation of neuronal
genes by CtBP will open avenues of therapy for neurological disorders and cancer.
PMID- 17041594
TI - Phase-locking of hippocampal interneurons' membrane potential to neocortical up
down states.
AB - During quiet wakefulness and sleep, and under anesthesia, the membrane potentials
of neocortical pyramidal neurons show synchronous, slow oscillations, so-called
up-down states (UDS), that can be detected in the local field potential (LFP).
The influence of this synchronized, spontaneous neocortical activity on the
hippocampus is largely unknown. We performed the first in vivo whole-cell
recordings from hippocampal dorsal CA1 interneurons and found that their membrane
potentials were phase-locked to neocortical up-down states with a small delay.
These results provide strong evidence for cortico-hippocampal interaction and
suggest that neocortical activity drives hippocampal interneurons during UDS.
PMID- 17041595
TI - How MT cells analyze the motion of visual patterns.
AB - Neurons in area MT (V5) are selective for the direction of visual motion. In
addition, many are selective for the motion of complex patterns independent of
the orientation of their components, a behavior not seen in earlier visual areas.
We show that the responses of MT cells can be captured by a linear-nonlinear
model that operates not on the visual stimulus, but on the afferent responses of
a population of nonlinear V1 cells. We fit this cascade model to responses of
individual MT neurons and show that it robustly predicts the separately measured
responses to gratings and plaids. The model captures the full range of pattern
motion selectivity found in MT. Cells that signal pattern motion are
distinguished by having convergent excitatory input from V1 cells with a wide
range of preferred directions, strong motion opponent suppression and a tuned
normalization that may reflect suppressive input from the surround of V1 cells.
PMID- 17041596
TI - Interleukin-10 determines viral clearance or persistence in vivo.
AB - Persistent viral infections are a major health concern. One obstacle inhibiting
the clearance of persistent infections is functional inactivation of antiviral T
cells. Although such immunosuppression occurs rapidly after infection, the
mechanisms that induce the loss of T-cell activity and promote viral persistence
are unknown. Herein we document that persistent viral infection in mice results
in a significant upregulation of interleukin (IL)-10 by antigen-presenting cells,
leading to impaired T-cell responses. Genetic removal of Il10 resulted in the
maintenance of robust effector T-cell responses, the rapid elimination of virus
and the development of antiviral memory T-cell responses. Therapeutic
administration of an antibody that blocks the IL-10 receptor restored T-cell
function and eliminated viral infection. Thus, we identify a single molecule that
directly induces immunosuppression leading to viral persistence and demonstrate
that a therapy to neutralize IL-10 results in T-cell recovery and the prevention
of viral persistence.
PMID- 17041597
TI - Oriented loading of FtsK on KOPS.
AB - In Escherichia coli, the ATP-dependent DNA translocase FtsK transports DNA across
the site of cell division and activates recombination by the XerCD recombinases
at a specific site on the chromosome, dif, to ensure the last stages of
chromosome segregation. DNA transport by FtsK is oriented by 8-base-pair
asymmetric sequences ('KOPS'). Here we provide evidence that KOPS promote FtsK
loading on DNA and that translocation is oriented at this step.
PMID- 17041598
TI - Identification of the FtsK sequence-recognition domain.
AB - FtsK is a prokaryotic multidomain DNA translocase that coordinates chromosome
segregation and cell division. FtsK is membrane anchored at the division septum
and, guided by highly skewed DNA sequences, translocates the chromosome to bring
the terminus of replication to the septum. Here, we use in vitro single-molecule
and ensemble methods to unveil a mechanism of action in which the translocation
and sequence-recognition activities are performed by different domains in FtsK.
PMID- 17041599
TI - Structural and biochemical basis for misfolded RNA recognition by the Ro
autoantigen.
AB - The Ro autoantigen is ring-shaped, binds misfolded noncoding RNAs and is proposed
to function in quality control. Here we determine how Ro interacts with misfolded
RNAs. Binding of Ro to misfolded precursor (pre)-5S ribosomal RNA requires a
single-stranded 3' end and helical elements. As mutating most sequences of the
helices and tail results in modest decreases in binding, Ro may be able to
associate with a range of RNAs. Ro binds several other RNAs that contain single
stranded tails. A crystal structure of Ro bound to a misfolded pre-5S rRNA
fragment reveals that the tail inserts into the cavity, while a helix binds on
the surface. Most contacts of Ro with the helix are to the backbone. Mutagenesis
reveals that Ro has an extensive RNA-binding surface. We propose that Ro uses
this surface to scavenge RNAs that fail to bind their specific RNA-binding
proteins.
PMID- 17041600
TI - R-spondin1 is essential in sex determination, skin differentiation and
malignancy.
AB - R-spondins are a recently characterized small family of growth factors. Here we
show that human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome
characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition
to squamous cell carcinoma of the skin. Our data show, for the first time, that
disruption of a single gene can lead to complete female-to-male sex reversal in
the absence of the testis-determining gene, SRY.
PMID- 17041601
TI - Abnormal skin, limb and craniofacial morphogenesis in mice deficient for
interferon regulatory factor 6 (Irf6).
AB - Transcription factor paralogs may share a common role in staged or overlapping
expression in specific tissues, as in the Hox family. In other cases, family
members have distinct roles in a range of embryologic, differentiation or
response pathways (as in the Tbx and Pax families). For the interferon regulatory
factor (IRF) family of transcription factors, mice deficient in Irf1, Irf2, Irf3,
Irf4, Irf5, Irf7, Irf8 or Irf9 have defects in the immune response but show no
embryologic abnormalities. Mice deficient for Irf6 have not been reported, but in
humans, mutations in IRF6 cause two mendelian orofacial clefting syndromes, and
genetic variation in IRF6 confers risk for isolated cleft lip and palate. Here we
report that mice deficient for Irf6 have abnormal skin, limb and craniofacial
development. Histological and gene expression analyses indicate that the primary
defect is in keratinocyte differentiation and proliferation. This study describes
a new role for an IRF family member in epidermal development.
PMID- 17041602
TI - Essential role of Jun family transcription factors in PU.1 knockdown-induced
leukemic stem cells.
AB - Knockdown of the transcription factor PU.1 (encoded by Sfpi1) leads to acute
myeloid leukemia (AML) in mice. We examined the transcriptome of preleukemic
hematopoietic stem cells (HSCs) in which PU.1 was knocked down (referred to as
'PU.1-knockdown HSCs') to identify transcriptional changes preceding malignant
transformation. Transcription factors c-Jun and JunB were among the top
downregulated targets. Restoration of c-Jun expression in preleukemic cells
rescued the PU.1 knockdown-initiated myelomonocytic differentiation block.
Lentiviral restoration of JunB at the leukemic stage led to loss of leukemic self
renewal capacity and prevented leukemia in NOD-SCID mice into which leukemic PU.1
knockdown cells were transplanted. Examination of human individuals with AML
confirmed the correlation between PU.1 and JunB downregulation. These results
delineate a transcriptional pattern that precedes leukemic transformation in PU.1
knockdown HSCs and demonstrate that decreased levels of c-Jun and JunB contribute
to the development of PU.1 knockdown-induced AML by blocking differentiation and
increasing self-renewal. Therefore, examination of disturbed gene expression in
HSCs can identify genes whose dysregulation is essential for leukemic stem cell
function and that are targets for therapeutic interventions.
PMID- 17041603
TI - Irf6 is a key determinant of the keratinocyte proliferation-differentiation
switch.
AB - The epidermis is a highly organized structure, the integrity of which is central
to the protection of an organism. Development and subsequent maintenance of this
tissue depends critically on the intricate balance between proliferation and
differentiation of a resident stem cell population; however, the signals
controlling the proliferation-differentiation switch in vivo remain elusive.
Here, we show that mice carrying a homozygous missense mutation in interferon
regulatory factor 6 (Irf6), the homolog of the gene mutated in the human
congenital disorders Van der Woude syndrome and popliteal pterygium syndrome,
have a hyperproliferative epidermis that fails to undergo terminal
differentiation, resulting in soft tissue fusions. We further demonstrate that
mice that are compound heterozygotes for mutations in Irf6 and the gene encoding
the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3sigma) show
similar defects of keratinizing epithelia. Our results indicate that Irf6 is a
key determinant of the keratinocyte proliferation-differentiation switch and that
Irf6 and Sfn interact genetically in this process.
PMID- 17041604
TI - The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt
signaling, is mutated in inherited anonychia.
AB - Anonychia and hyponychia congenita (OMIM 206800) are rare autosomal recessive
conditions in which the only presenting phenotype is the absence or severe
hypoplasia of all fingernails and toenails. After determining linkage to
chromosome 20p13, we identified homozygous or compound heterozygous mutations in
the gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt
signaling, in eight affected families. Rspo4 expression was specifically
localized to developing mouse nail mesenchyme at embryonic day 15.5, suggesting a
crucial role in nail morphogenesis.
PMID- 17041605
TI - Interface-disrupting amino acids establish specificity between T cell receptors
and complexes of major histocompatibility complex and peptide.
AB - T cell receptors (TCRs) bind complexes of cognate major histocompatibility
complex (MHC) and peptide at relatively low affinities (1-200 microM).
Nevertheless, TCR-MHC-peptide interactions are usually specific for the peptide
and the allele encoding the MHC. Here we show that to escape thymocyte negative
selection, TCRs must interact with many of the side chains of MHC-peptide
complexes as 'hot spots' for TCR binding. Moreover, even when the 'parental' side
chain did not contribute binding affinity, some MHC-peptide residues contributed
to TCR specificity, as amino acid substitutions substantially reduced binding
affinity. The presence of such 'interface-disruptive' side chains helps to
explain how TCRs generate specificity at low-affinity interfaces and why TCRs
often 'accommodate' a subset of amino acids at a given MHC-peptide position.
PMID- 17041606
TI - Low mortality of children undergoing hematopoietic stem cell transplantation from
7 to 8/10 human leukocyte antigen allele-matched unrelated donors with the use of
antithymocyte globulin.
AB - Human leukocyte antigen (HLA)-matched sibling donor hematopoietic stem cell
transplantation (HSCT) is available for only approximately 30% patients needing
HSCT. Use of alternative donors is associated with a high incidence and severity
of graft-versus-host disease (GVHD). Here we report our experience with GVHD
prophylaxis using pre-transplant rabbit antithymocyte globulin (rATG), in
addition to post transplant cyclosporin A and methotrexate. Seventy-five children
received unmanipulated grafts from 7 to 10/10 HLA allele-matched unrelated
donors. Median follow-up was 25 months (range, 6-65 months). Only 2/75 patients
(2.5%) developed acute GVHD grades III-IV, and 17/75 (25%) developed extensive
chronic GVHD. Overall survival was 79%. It was similar in patients receiving
grafts from 7 or 8/10 to 9 or 10/10 allele-matched donors, and similar in
patients receiving peripheral blood stem cells and marrow. Six (11%) patients
died owing to relapse, and 10 (13%) due to transplant-related complications. The
addition of rATG appears to result in a low incidence of severe GVHD and overall
mortality.
PMID- 17041607
TI - Addressing parenting concerns of bone marrow transplant patients: opening (and
closing) Pandora's box.
AB - Although a significant number of adults undergoing stem cell transplant (SCT) or
bone marrow transplantation (BMT) care for dependent children, and these
treatments pose significant challenges for families, research has virtually
ignored the impact of parenting on patients' quality of life during BMT/SCT and
children's responses to having a parent undergo these treatments. Physicians
rarely inquire about parenting concerns related to the extended hospitalizations
necessitated by these treatments, yet clinical experience suggests that
addressing patient concerns about children's reactions to cancer and BMT/SCT can
improve the experience of the patient and the patient's family, and help the
medical team respond effectively to sources of patients' distress. Parents
frequently want to know what reactions to expect from children, thus general
developmental information is reviewed, and recommendations given for when
professional help for children is warranted. A key way for parents to support
their children is with open, honest communication; however, parents often find it
extremely difficult to talk about cancer and BMT/SCT with their children. The
medical team can assist patients' efforts to communicate with and support their
children by asking about a patient's children, providing some targeted
information, and discussing the potential impact of treatments on parenting
capacity. Inquiring about and addressing parenting concerns may initially seem
difficult, but can ultimately facilitate stronger doctor-patient alliances, and
more compassionate care.
PMID- 17041608
TI - Bone marrow transplantation for cartilage-hair-hypoplasia.
AB - The association of cartilage hair hypoplasia (CHH) with severe combined
immunodeficiency (SCID) has been known for more than three decades. Bone marrow
transplantation (BMT) remains the only effective treatment that might cure SCID.
Surprisingly little has been reported on the experience with BMT in CHH. We
report here survival and long-term reconstitution of immunity after BMT in three
patients with CHH. Regardless of whether a related human leukocyte antigen
matched or unrelated matched donors were used as the source of BMT, all patients
are alive and well 5-20 years after BMT. Engraftment appears robust with most
cells of donors origin. Repeated evaluation of the immune system showed normal
cellular and humoral immunity. Our results should encourage the use of BMT in
patients with CHH who have profound immunodeficiency.
PMID- 17041609
TI - Autologous stem cell transplantation beyond 60 years of age.
AB - Along with improved supportive care and thus reduced treatment-related mortality,
an increasing number of elderly patients (> 60 years) with haematological
malignancies are now considered for high-dose therapy (HDT) supported by
autologous stem cell transplantation (ASCT). ASCT is feasible in selected elderly
patients with multiple myeloma and those with non-Hodgkin's lymphoma. As elderly
patients have generally been excluded from randomized studies evaluating efficacy
of ASCT in comparison with non-transplant approaches, limited data are available
on the efficacy of ASCT in this patient population. Recent developments in
supportive care including amifostine and palifermin may increase feasibility of
ASCT in elderly patients. Prospective studies are needed to evaluate feasibility
and efficacy of ASCT in patients over 60 years of age. Also, further studies are
needed in order to decrease toxicity of high-dose regimens in this patient group
where co-morbid conditions may modify the toxicity of HDT in a clinically
significant manner.
PMID- 17041610
TI - Iron homeostasis in plants: when transcription affects translocation.
PMID- 17041612
TI - The increasing importance of systematic reviews in clinical dermatology research
and publication.
PMID- 17041616
TI - CD95-mediated signals in the skin: going out with an (inflammatory) bang?
AB - The death ligand CD95L (Fas/Apo-1-ligand) has been viewed as a proapoptotic
molecule involved in the pathogenesis of T cell-mediated skin diseases including
eczema. In the presence of inhibitors of caspases, CD95L induces proinflammatory
genes in keratinocytes. This more pleiotropic function of CD95L as enhancer of
inflammation may be equally important to apoptosis induction of keratinocytes, at
least in eczema.
PMID- 17041617
TI - The new keratin nomenclature.
AB - When the first nomenclature of the keratin protein family was published over 20
years ago, only 19 keratins were thought to exist. Sequencing of the human genome
has now revealed that there are 54 keratin genes. As a consequence, the
nomenclature needed revision to apply a logical numbering system that includes
the more recently identified keratins of the hair follicle.
PMID- 17041618
TI - A new nail in the CTCL coffin.
AB - The impact of immunotherapy on the natural progression of cutaneous T-cell
lymphoma (CTCL), particularly the mycosis fungoides and Sezary syndrome variants,
has been based on our evolving understanding of the disease's immunobiology.
PMID- 17041621
TI - Upstream of the mammalian target of rapamycin: do all roads pass through mTOR?
AB - The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that
controls many aspects of cellular physiology, including transcription,
translation, cell size, cytoskeletal organization and autophagy. Recent advances
in the mTOR signaling field have found that mTOR exists in two heteromeric
complexes, mTORC1 and mTORC2. The activity of mTORC1 is regulated by the
integration of many signals, including growth factors, insulin, nutrients, energy
availability and cellular stressors such as hypoxia, osmotic stress, reactive
oxygen species and viral infection. In this review we highlight recent advances
in the mTOR signaling field that relate to how the two mTOR complexes are
regulated, and we discuss stress conditions linked to the mTOR signaling network
that have not been extensively covered in other reviews. Given the diversity of
signals that have been shown to impinge on mTOR, we also speculate on other
signal-transduction pathways that may be linked to mTOR in the future.
PMID- 17041622
TI - Insulin and amino-acid regulation of mTOR signaling and kinase activity through
the Rheb GTPase.
AB - Target of Rapamycin (TOR), a giant protein kinase expressed by all eucaryotic
cells, controls cell size in response to nutrient signals. In metazoans, cell and
organismal growth is controlled by nutrients and the insulin/insulin-like growth
factor (IGF) system, and the understanding of how these inputs coordinately
regulate TOR signaling has advanced greatly in the past 5 years. In single-cell
eucaryotes and Caenorhabditis elegans, TOR is a dominant regulator of overall
mRNA translation, whereas in higher metazoans, TOR controls the expression of a
smaller fraction of mRNAs that is especially important to cell growth. TOR
signals through two physically distinct multiprotein complexes, and the control
of cell growth is mediated primarily by TOR complex 1 (TORC1), which contains the
polypeptides raptor and LST8. Raptor is the substrate binding element of TORC1,
and the ability of raptor to properly present substrates, such as the
translational regulators 4E-BP and p70 S6 kinase, to the TOR catalytic domain is
essential for their TOR-catalysed phosphorylation, and is inhibited by the
Rapamycin/FKBP-12 complex. The dominant proximal regulator of TORC1 signaling and
kinase activity is the ras-like small GTPase Rheb. Rheb binds directly to the
mTOR catalytic domain, and Rheb-GTP enables TORC1 to attain an active
configuration. Insulin/IGF enhances Rheb GTP charging through the ability of
activated Akt to inhibit the Rheb-GTPase-activating function of the tuberous
sclerosis heterodimer (TSC1/TSC2). Conversely, energy depletion reduces Rheb-GTP
charging through the ability of the adenosine monophosphate-activated protein
kinase to phosphorylate TSC2 and stimulate its Rheb-GTPase activating function,
as well as by HIFalpha-mediated transcriptional responses that act upstream of
the TSC1/2 complex. Amino-acid depletion inhibits TORC1 acting predominantly
downstream of the TSC complex, by interfering with the ability of Rheb to bind to
mTOR. The components of the insulin/IGF pathway to TORC1 are now well
established, whereas the elements mediating the more ancient and functionally
dominant input of amino acids remain largely unknown.
PMID- 17041623
TI - Stress and mTORture signaling.
AB - The TOR (target of rapamycin) pathway is an evolutionarily conserved signaling
module regulating cell growth (accumulation of mass) in response to a variety of
environmental cues such as nutrient availability, hypoxia, DNA damage and osmotic
stress. Its pivotal role in cellular and organismal homeostasis is reflected in
the fact that unrestrained signaling activity in mammals is associated with the
occurrence of disease states including inflammation, cancer and diabetes. The
existence of TOR homologs in unicellular organisms whose growth is affected by
environmental factors, such as temperature, nutrients and osmolarity, suggests an
ancient role for the TOR signaling network in the surveillance of stress
conditions. Here, we will summarize recent advances in the TOR signaling field
with special emphasis on how stress conditions impinge on insulin/insulin-like
growth factor signaling/TOR signaling.
PMID- 17041624
TI - Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three
classes of nuclear RNA polymerases.
AB - The target of rapamycin (TOR) signal-transduction pathway is an important
mechanism by which eucaryotic cells adjust their protein biosynthetic capacity to
nutrient availability. Both in yeast and in mammals, the TOR pathway regulates
the synthesis of ribosomal components, including transcription and processing of
pre-rRNA, expression of ribosomal proteins and the synthesis of 5S rRNA.
Expression of the genes encoding the numerous constituents of ribosomes requires
transcription by all three classes of nuclear RNA polymerases. In this review, we
summarize recent advances in understanding the interplay among nutrient
availability, transcriptional control and ribosome biogenesis. We focus on
transcription in response to nutrients, detailing the relevant downstream targets
of TOR in yeast and mammals. The critical role of TOR in linking environmental
queues to ribosome biogenesis provides an efficient means by which cells alter
their overall protein biosynthetic capacity.
PMID- 17041625
TI - Cell growth control: little eukaryotes make big contributions.
AB - The story of rapamycin is a pharmaceutical fairytale. Discovered as an antifungal
activity in a soil sample collected on Easter Island, this macrocyclic lactone
and its derivatives are now billion dollar drugs, used in, and being evaluated
for, a number of clinical applications. Taking advantage of its antifungal
property, the molecular Target Of Rapamycin, TOR, was first described in the
budding yeast Saccharomyces cerevisiae. TORs encode large, Ser/Thr protein
kinases that reside in two distinct, structurally and functionally conserved,
multi-protein complexes. In yeast, these complexes coordinate many different
aspects of cell growth. TOR complex 1, TORC1, promotes protein synthesis and
other anabolic processes, while inhibiting macroautophagy and other catabolic and
stress-response processes. TORC2 primarily regulates cell polarity, although
additional readouts of this complex are beginning to be characterized. TORC1
appears to be activated by nutrient cues and inhibited by stresses and rapamycin;
however, detailed mechanisms are not known. In contrast, TORC2 is insensitive to
rapamycin and physiological regulators of this complex have yet to be defined.
Given the unsurpassed resources available to yeast researchers, this simple
eukaryote continues to contribute to our understanding of eukaryotic cell growth
in general and TOR function in particular.
PMID- 17041626
TI - mTOR, translation initiation and cancer.
AB - Control of mRNA translation plays a fundamental role in many aspects of cell
metabolism. It constitutes a critical step in the control of gene expression, and
consequently cell growth, proliferation and differentiation. Translation is
regulated in response to nutrient availability, hormones, mitogenic and growth
factor stimulation and is coupled with cell cycle progression and cell growth.
Signaling by the PI3K/Akt/mTOR pathway profoundly affects mRNA translation
through phosphorylation of downstream targets such as 4E-BP and S6K. Inhibitors
of this pathway and thus cap-dependent translation are emerging as promising
therapeutic options for the treatment of cancer.
PMID- 17041627
TI - When translation meets transformation: the mTOR story.
AB - There is currently a high level of interest in signalling through the mammalian
target of rapamycin (mTOR). This reflects both its key role in many cell
functions and its involvement in disease states such as cancers. The best
understood targets for mTOR signalling are proteins involved in controlling the
translational machinery, including the ribosomal protein S6 kinases and proteins
that regulate the initiation and elongation phases of translation. Indeed, there
is compelling evidence that at least one of these targets of mTOR (eukaryotic
initiation factor eIF4E) plays a key role in tumorigenesis. It is regulated
through the mTOR-dependent phosphorylation of inhibitory proteins such as eIF4E
binding protein 1. Thus, targeting mTOR signalling may be an effective anticancer
strategy, in at least a significant subset of tumours. Not all effects of mTOR
are sensitive to the classical anti-mTOR drug rapamycin, and this compound also
interferes with other processes besides eIF4E function. Developing new approaches
to targeting mTOR for cancer therapy requires more detailed knowledge of
signalling downstream of mTOR. Such advances are likely to come from further work
to understand the regulation of mTOR targets such as components of the
translational apparatus.
PMID- 17041628
TI - mTOR and cancer therapy.
AB - Proteins regulating the mammalian target of rapamycin (mTOR), as well as some of
the targets of the mTOR kinase, are overexpressed or mutated in cancer.
Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of
recently developed rapamycin analogs (rapalogs) consisting of synthetically
derived compounds containing minor chemical modifications to the parent
structure, inhibit the growth of cell lines derived from multiple tumor types in
vitro, and tumor models in vivo. Results from clinical trials indicate that the
rapalogs may be useful for the treatment of subsets of certain types of cancer.
The sporadic responses from the initial clinical trials, based on the hypothesis
of general translation inhibition of cancer cells are now beginning to be
understood owing to a more complete understanding of the dynamics of mTOR
regulation and the function of mTOR in the tumor microenvironment. This review
will summarize the preclinical and clinical data and recent discoveries of the
function of mTOR in cancer and growth regulation.
PMID- 17041629
TI - The type III secretion injectisome.
AB - The type III secretion injectisome is a complex nanomachine that allows bacteria
to deliver protein effectors across eukaryotic cellular membranes. In recent
years, significant progress has been made in our understanding of its structure,
assembly and mode of operation. The principal structural components of the
injectisome, from the base located in the bacterial cytosol to the tip of the
needle protruding from the cell surface, have been investigated in detail. The
structures of several constituent proteins were solved at the atomic level and
important insights into the assembly process have been gained. However, despite
the ongoing concerted efforts of molecular and structural biologists, the role of
many of the constituent components of this nanomachine remain unknown.
PMID- 17041630
TI - Bacterial populations as perfect gases: genomic integrity and diversification
tensions in Helicobacter pylori.
AB - Microorganisms that persist in single hosts face particular challenges.
Helicobacter pylori, an obligate bacterial parasite of the human stomach, has
evolved a lifestyle that features interstrain competition and intraspecies
cooperation, both of which involve horizontal gene transfer. Microbial species
must maintain genomic integrity, yet H. pylori has evolved a complex nonlinear
system for diversification that exists in dynamic tension with the mechanisms for
ensuring fidelity. Here, we review these tensions and propose that they create a
dynamic pool of genetic variants that is sufficiently genetically diverse to
allow H. pylori to occupy all of the potential niches in the stomach.
PMID- 17041631
TI - Viruses of the Archaea: a unifying view.
AB - DNA viruses of the Archaea have highly diverse and often exceptionally complex
morphotypes. Many have been isolated from geothermally heated hot environments,
raising intriguing questions about their origins, and contradicting the
widespread notion of limited biodiversity in extreme environments. Here, we
provide a unifying view on archaeal viruses, and present them as a particular
assemblage that is fundamentally different in morphotype and genome from the DNA
viruses of the other two domains of life, the Bacteria and Eukarya.
PMID- 17041632
TI - The silent path to thousands of merozoites: the Plasmodium liver stage.
AB - Plasmodium sporozoites are deposited in the skin of their vertebrate hosts
through the bite of an infected female Anopheles mosquito. Most of these
parasites find a blood vessel and travel in the peripheral blood circulation
until they reach the liver sinusoids. Once there, the sporozoites cross the
sinusoidal wall and migrate through several hepatocytes before they infect a
final hepatocyte, with the formation of a parasitophorous vacuole, in which the
intrahepatic form of the parasite grows and multiplies. During this period, each
sporozoite generates thousands of merozoites. As the development of Plasmodium
sporozoites inside hepatocytes is an obligatory step before the onset of disease,
understanding the parasite's requirements during this period is crucial for the
development of any form of early intervention. This Review summarizes our current
knowledge on this stage of the Plasmodium life cycle.
PMID- 17041634
TI - Reduced-intensity conditioning allogeneic stem cell transplantation: hype,
reality or time for a rethink?
PMID- 17041633
TI - Genomics meets HIV-1.
AB - Genomics is now a core element in the effort to develop a vaccine against HIV-1.
Thanks to unprecedented progress in high-throughput genotyping and sequencing, in
knowledge about genetic variation in humans, and in evolutionary genomics, it is
finally possible to systematically search the genome for common genetic variants
that influence the human response to HIV-1. The identification of such variants
would help to determine which aspects of the response to the virus are the most
promising targets for intervention. However, a key obstacle to progress remains
the scarcity of appropriate human cohorts available for genomic research.
PMID- 17041635
TI - Difference between hematological malignancy and solid tumor research articles
published in four major medical journals.
PMID- 17041636
TI - Towards defining the lymphoma methylome.
PMID- 17041637
TI - Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia.
AB - The cells of solid tumours are known to have an altered metabolism, with high
rates of glucose uptake and glycolysis, which results in the excessive production
of lactate. To date there has been no definitive research documenting metabolic
changes in acute lymphoblastic leukaemia (ALL) cells. In order to investigate
whether ALL cells have an altered metabolism, we initially compared the
transcriptional profiles of 22 specimens from paediatric patients diagnosed with
ALL to five CD34+ specimens isolated from bone marrow, which was verified in an
independent cohort of 101 specimens. Profiling revealed the upregulation of genes
facilitating glycolysis in the ALL specimens compared to the CD34+ specimens,
while those involved in the tricarboxylic acid cycle were downregulated.
Functional studies supported the microarray findings threefold: (1) higher
expression of the glucose transport protein glucose transporter 1 in ALL compared
to CD34+ specimens, (2) the excessive production of lactate in ALL cell lines and
(3) sensitivity of ALL cell lines to the glycolysis inhibitor 2-deoxy-D-glucose.
While metabolic alterations have been well documented in solid tumours, this is
the first study to provide direct evidence for the existence of metabolic changes
in the leukaemic cells of ALL patients. The finding offers new options for
targeted therapy for ALL patients.
PMID- 17041639
TI - Rapid and sensitive typing of NPM1 mutations using LNA-mediated PCR clamping.
PMID- 17041638
TI - Characterization of an artificial antigen-presenting cell to propagate cytolytic
CD19-specific T cells.
PMID- 17041640
TI - Estimation of the power scintillation probability density function in free-space
optical links by use of multicanonical Monte Carlo sampling.
AB - Free-space optics (FSO) can provide cost-effective, high-bandwidth, wireless
connections. However, atmospheric turbulence may degrade the performance of FSO
links by causing intensity and power scintillations at the receiver.
Multicanonical Monte Carlo sampling is used in conjunction with the phase screen
method to calculate the statistics, and particularly the probability density
function (PDF), of the power fluctuations at an FSO receiver. This allows the
efficient calculation of the PDF even for very small values with a limited number
of iterations. The obtained PDF can be used to characterize the performance of
the system in terms of the error probability.
PMID- 17041641
TI - Rotational frequency shifts for electromagnetic fields of arbitrary states of
coherence and polarization.
AB - The rotational frequency shift is studied for fields of arbitrary states of
coherence and polarization. It is shown that the power spectrum of the field in
the rotating frame is influenced both by the degree of polarization and the
degree of coherence. Examples for some model field classes are given.
PMID- 17041642
TI - Optical ultrawideband monocycle pulse generation based on cross-gain modulation
in a semiconductor optical amplifier.
AB - A novel method for generating ultrawideband (UWB) monocycle pulses based on cross
gain modulation (XGM) in a semiconductor optical amplifier (SOA) is proposed and
experimentally demonstrated. Thanks to the XGM in the SOA, a pair of polarity
reversed optical Gaussian pulses is generated at the output of the SOA, to which
a Gaussian pulse pump and a continuous-wave probe are applied. The two polarity
reversed optical pulses are then time delayed by two cascaded fiber Bragg
gratings to introduce a time delay difference. A UWB monocycle pulse with a full
width at half-maximum of 48 ps and a fractional bandwidth of 188% is generated at
the output of a high-speed photodetector.
PMID- 17041643
TI - Raman response function for silica fibers.
AB - The commonly used Lorentzian form of the Raman response function for studying
propagation of ultrashort pulses in silica fibers does not properly account for
the shoulder in the Raman gain spectrum originating from the Boson peak. We
propose a more accurate form of this response function and show that its
predictions for the Raman-induced frequency shift should be in better agreement
with experiments.
PMID- 17041644
TI - Absorption as a selective mechanism in surface plasmon resonance fiber optic
sensors.
AB - A new concept of surface plasmon resonance fiber optic sensor is presented. By
tuning the plasmon resonance to a wavelength for which the outer medium is
absorptive, a significant variation of the spectral transmittance of the device
is produced as a function of the concentration of the analyte. With this
mechanism, selectivity can be achieved without the need of any functionalization
of the surfaces or the use of recognizing elements, which is a very interesting
feature for any kind of chemical sensor or biosensor. Doubly deposited uniform
waist tapered fibers are well suited for the development of these new sensors.
Multiple surface plasmon resonance, obtainable in those structures, can be used
for the development of microspectrometers based on this principle.
PMID- 17041645
TI - Slowing down of solitons by intrapulse Raman scattering in fibers with frequency
cutoff.
AB - A method for transforming fast solitons into slow ones in bandgap fibers is
proposed. The approach is based on the deceleration of the solitons by intrapulse
Raman scattering, which can be achieved for fiber modes having a cutoff
frequency. We develop a comprehensive theory for the soliton slowdown and
elucidate how the fiber losses introduce a fundamental minimum for the soliton
velocity.
PMID- 17041646
TI - Submicrometer digital in-line holographic microscopy at 32 nm with high-order
harmonics.
AB - Soft-x-ray digital in-line microscopic holography is achieved using a fully
coherent high-order harmonic source emitting at 32 nm. Combination of commercial
grade soft-x-ray optics and a back-illuminated CCD detector allows a compact and
versatile holographic setup. Different experimental geometries have been tested
by imaging calibrated 50 nm tips and 1 microm wires. Spatial resolution of 800 nm
is measured with magnifications ranging from 30 to 110 and a numerical aperture
around 0.01. Finally, the potentiality of three-dimensional numerical
reconstruction from a single hologram acquisition is shown experimentally.
PMID- 17041647
TI - Spectrally resolved phase-shifting interferometry for accurate group-velocity
dispersion measurements.
AB - We report an accurate method to measure the group-velocity dispersion (GVD) of
transparent materials by use of spectrally resolved phase-shifting
interferometry. The GVD of silica glass slide measured using an eight-step phase
shifting algorithm agrees well with that calculated using the Sellmeier
dispersion equation over the entire visible wavelength region, with a rms error
of < or =0.0036 microm(-2), better than that of other measurement methods
reported so far.
PMID- 17041648
TI - Frequency-comb-referenced two-wavelength source for absolute distance
measurement.
AB - We propose a new tunable laser source concept for multiple-wavelength
interferometry, offering an unprecedented large choice of synthetic wavelengths
with a relative uncertainty better than 10(-11) in vacuum. Two lasers are
frequency stabilized over a wide range of frequency intervals defined by the
frequency comb generated by a mode-locked fiber laser. In addition, we present
experimental results demonstrating the generation of a 90 mum synthetic
wavelength calibrated with an accuracy better than 0.2 parts in 10(6). With this
synthetic wavelength we can resolve one optical wavelength, which opens the way
to absolute distance measurement with nanometer accuracy.
PMID- 17041649
TI - Polarization beam splitter based on a photonic crystal heterostructure.
AB - The design and characterization of a photonic crystal (PC) polarization beam
splitter (PBS) that operates with an extinction ratio of greater than 15 dB for
both polarizations are presented. The PBS is fabricated on a silicon-on-insulator
(SOI) wafer where the input and output ports consist of 5 mum wide ridge
waveguides. A large spectral shift is observed in the dispersion plots of the
lowest-order even (TE-like) and odd (TM-like) modes due to the SOI confinement.
Because of this shift, the TE-like mode is close to a directional gap at the top
of the band, and the TM-like mode is in a low-frequency regime where the
dispersion surface is almost isotropic. We show that the TE-like mode has very
high reflection at the interface between the two PCs, whereas the TM-like mode
exhibits a very high transmission.
PMID- 17041650
TI - Simultaneous achievement of narrow pulse width and low pulse-to-pulse timing
jitter in 1.3 microm passively mode-locked quantum-dot lasers.
AB - We have analyzed pulse width and timing jitter in passively mode-locked two
section InAs quantum-dot lasers emitting at 1310 nm and have identified two
distinct, extensive mode-locked regions with robust short pulses and low timing
jitter. A record combination of 2 ps pulses and 25 fs/cycle timing jitter (500
fs, 1-100 MHz), with 1 mW average output power per facet, is demonstrated.
PMID- 17041651
TI - Expedited laser damage profiling of KDxH(2-x)PO4 with respect to crystal growth
parameters.
AB - We investigate the laser-induced damage resistance at 355 nm in deuterated
potassium dihydrogen phosphate (DKDP) crystals grown with varying growth
parameters, including speed of growth and temperature. The aim is to explore a
new expedited method to study the growth parameters affecting the laser-induced
damage resistance in DKDP material to obtain crystals with enhanced performance.
PMID- 17041652
TI - Carrier-envelope phase shift caused by variation of grating separation.
AB - The effects of variation of the grating separation in a stretcher on the carrier
envelope (CE) phase of amplified pulses are investigated. By translating one of
the telescope mirrors in the stretcher with a piezoelectric transducer, it is
found that a 1 mum change of the distance causes a 3.7+/-1.2 rad shift of the CE
phase, which is consistent with theoretical estimations. The results indicate
that optical mounts used for gratings and telescope mirrors must be
interferometrically stable; otherwise their vibration and thermal drift will
cause significant phase error. The CE phase drift was corrected by feedback
controlling the grating separation.
PMID- 17041653
TI - 110 W double-ended ytterbium-doped fiber superfluorescent source with M2 = 1.6.
AB - High-power operation of a broadband superfluorescent fiber source has been
achieved via the process of amplified spontaneous emission (ASE) in a double-clad
Yb-doped multimode-offset-core fiber by using a novel fiber-end termination
geometry to suppress lasing. The fiber was cladding pumped by a high-power diode
source at 976 nm and yielded a maximum ASE output of 63 and 47 W from the two
ends of the fiber, respectively. The maximum combined ASE output was 110 W with
slope efficiency with respect to launched pump power of up to 68%. The wavelength
spectrum of the ASE source spanned the range from approximately 1032 to 1120 nm,
and the bandwidth (FWHM) of the emission spectrum was 40 nm. The output beam was
slightly multimode with a beam-quality factor (M2) of 1.6. The prospects for
further improvement in performance are considered.
PMID- 17041655
TI - Sensing cell metabolism by time-resolved autofluorescence.
AB - We built a time-resolved confocal fluorescence spectroscopy system equipped with
the multichannel time-correlated single-photon-counting technique. The instrument
provides a unique approach to study the fluorescence sensing of cell metabolism
via analysis of the wavelength- and time-resolved intracellular autofluorescence.
The experiments on monolayered cell cultures show that with UV excitation at 365
nm the time-resolved autofluorescence decays, dominated by free-bound reduced
nicotinamide adenine dinucleotide signals, are sensitive indicators for cell
metabolism. However, the sensitivity decreases with the increase of excitation
wavelength possibly due to the interference from free-bound flavin adenine
dinucleotide fluorescence. The results demonstrate that time-resolved
autofluorescence can be potentially used as an important contrast mechanism to
detect epithelial precancer.
PMID- 17041654
TI - Assessing epithelial cell nuclear morphology by using azimuthal light scattering
spectroscopy.
AB - We describe azimuthal light scattering spectroscopy (phi/LSS), a novel technique
for assessing epithelial-cell nuclear morphology. The difference between the
spectra measured at azimuthal angles phi = 0 degrees and phi = 90 degrees
preferentially isolates the single backscattering contribution due to large
(approximately 10 microm) structures such as epithelial cell nuclei by
discriminating against scattering from smaller organelles and diffusive
background. We demonstrate the feasibility of using phi/LSS for cancer detection
by showing that spectra from cancerous colon tissue exhibit significantly greater
azimuthal asymmetry than spectra from normal colonic tissues.
PMID- 17041656
TI - Polychromatic interface solitons in nonlinear photonic lattices.
AB - We demonstrate that interfaces between two nonlinear periodic photonic lattices
offer unique possibilities for controlling the nonlinear interaction between
different spectral components of polychromatic light, and a change in the light
spectrum can have a dramatic effect on the propagation along the interface. We
predict the existence of polychromatic surface solitons that differ fundamentally
from their counterparts in infinite lattices.
PMID- 17041657
TI - BiB3O6 femtosecond optical parametric oscillator.
AB - We report a femtosecond optical parametric oscillator (OPO) based on the
nonlinear material BiB3O6. The OPO is synchronously pumped in the blue by the
second harmonic of a Kerr-lens-mode-locked Ti:sapphire laser. It can provide wide
and continuous tuning across the entire green-yellow-orange-red spectral range
with a single crystal and a single set of mirrors. Using a 500 microm BiB3O6
crystal and collinear type I (e+e->o) phase matching in the optical yz plane, a
signal wavelength range of 480-710 nm is demonstrated with angle tuning at room
temperature at average output powers of 270 mW. With 220 fs blue pump pulses,
near-transform-limited signal pulses of 120 fs duration have been obtained at 76
MHz repetition rate.
PMID- 17041658
TI - Chaotic stimulated Brillouin scattering near the threshold in a fiber.
AB - We investigate the nonlinear dynamic behavior of stimulated Brillouin scattering
(SBS) near threshold in the absence of feedback. When a cw Nd:YAG laser is
injected into a single-mode optical fiber, the SBS signal exhibits intermittently
appearing irregular self-pulsations near the threshold. By examining the time
series of the SBS signals, we verify that the irregular SBS signal is one of the
chaotic phenomena appearing near the bifurcation point.
PMID- 17041659
TI - Planar-waveguide quasi-phase-matched second-harmonic-generation device in Y-cut
MgO-doped LiNbO3.
AB - We designed a planar-waveguide quasi-phase-matched second-harmonic-generation
device, which consists of a Y-cut periodically poled 5 mol.% MgO-doped LiNbO3
core and SiO2 claddings, that provided a 1.08 W green light with 30% conversion
efficiency by using a 7 mm long sample at room temperature. The highest
conversion efficiency of 49% at 0.88 W second-harmonic generation was attained by
using an 18 mm long device.
PMID- 17041660
TI - Vector soliton switching by using the cascade connection of saturable absorbers.
AB - We have numerically studied the cascade connection of a nonlinear amplifying loop
mirror and a length of birefringent fiber with two linear polarizers. This
structure is shown to work as a vector soliton switch under certain conditions.
After optimizing each structure separately, we show the improvement of the
switching response when the cascade connection is used. It is also demonstrated
that this design acts as a good intensity filter for vector soliton pulses.
PMID- 17041661
TI - Silicon waveguides for creating quantum-correlated photon pairs.
AB - We propose to use four-wave mixing inside silicon waveguides for generating
quantum-correlated photon pairs in a single spatial mode. Such silicon-based
photon sources not only exhibit high pair correlation but also have high spectral
brightness. As the proposed scheme is based on mature silicon technology, it has
the potential of becoming a cost-effective platform for on-chip quantum
information processing applications.
PMID- 17041662
TI - Nonlinear mirror based on cross-polarized wave generation.
AB - We present a new type of nonlinear mirror based on the generation of a cross
polarized wave through a nonresonant electronic third-order process. It is
characterized by a reflection coefficient that depends on the input intensity.
Its behavior results from the interference between the nonlinearly generated
cross-polarized wave and a pi/2 phase-retarded wave. This setup has a lot of
advantages: it does not require any phase matching, it is achromatic and suitable
for femtosecond pulses, linear losses are easily adjustable, and the overall
behavior is predictable. The device has been experimentally tested using BaF2 and
YVO4 crystals.
PMID- 17041663
TI - Quadratic phase matching in slot waveguides.
AB - We analyze phase matching with reference to frequency doubling in nanosized
quadratic waveguides encompassing form birefringence and supporting cross
polarized fundamental and second-harmonic modes. In an AlGaAs rod with an air
void, we show that phase-matched second-harmonic generation could be achieved in
a wide spectral range employing state-of-the-art nanotechnology.
PMID- 17041664
TI - 52 mJ narrow-bandwidth degenerated optical parametric system with a large
aperture periodically poled MgO:LiNbO3 device.
AB - We have demonstrated efficient, high-energy, narrow-spectral-bandwidth 2.128
microm pulse generation by use of periodically poled MgO:LiNbO3 devices with a 36
mm length and a 5 mm x 5 mm large aperture. A free-running degenerated optical
parametric oscillator (OPO) pumped with a Q-switched 1.064 microm Nd:YAG laser
exhibits a high slope efficiency of 75% and an optical-to-optical conversion
efficiency of 70% with a broad spectral bandwidth (>100 nm). In a configuration
with a spectrally narrowed master oscillator followed by a power amplifier, we
have achieved an output pulse energy of 52 mJ with a spectral bandwidth of less
than 2 nm at the degeneracy point. The total optical-to-optical conversion
efficiency of the system reached 50%.
PMID- 17041665
TI - Effect of photonic crystal structure on the nonlinear optical anisotropy of
birefringent porous silicon.
AB - Anisotropic photonic crystal structures consisting of birefringent porous silicon
layers with alternating porosity were fabricated. The in-plane birefringence
formed as a result of anisotropic etching in Si(110) results in unique
multilayered structures with two distinct photonic bandgaps for orthogonal light
polarizations. Nonlinear optical studies based on the third-harmonic generation
from these structures demonstrate variation in the symmetry of the nonlinear
optical response.
PMID- 17041666
TI - Multiscale Bessel beams generated by a tunable acoustic gradient index of
refraction lens.
AB - A beam that resembles a Bessel beam on two scales is generated using a tunable
acoustic gradient index of refraction (TAG) lens. The minor scale of the TAG
generated Bessel beam is nondiffracting and self-healing. The major scale of the
beam diffracts while still forming a Bessel pattern due to the specific geometry
of the TAG lens. The acoustic and optical theory behind the TAG lens is outlined,
and the experimental beam itself is presented. The major and minor rings are
explained, and the TAG beam is compared with both axicon-generated and
conventionally focused Gaussian beams.
PMID- 17041667
TI - Three-level phase modulator based on orthoconic antiferroelectric liquid
crystals.
AB - Surface-stabilized orthoconic antiferroelectric liquid crystals (OAFLCs) have a
director tilt of theta = 45 degrees and are, with no field applied, negatively
uniaxial with the optic axis perpendicular to the cell substrates. We demonstrate
that OAFLCs can be utilized to achieve lossless phase modulation with three
almost equidistant phase levels. This turns out to be true also for polymer
stabilized OAFLCs, where the polymer network increases the switching speed of the
device without affecting the phase modulation appreciably.
PMID- 17041668
TI - Slanted hole array beam profiler (SHArP)-a high-resolution portable beam profiler
based on a linear aperture array.
AB - We demonstrate a novel high-resolution portable beam profiler based on a slanted
linear array of small apertures, termed a slanted hole array beam profiler
(SHArP). The apertures are directly fabricated on a metal-coated CMOS imaging
sensor. With a single linear scan, the aperture array can establish a virtual
grid of sampling points for beam profiling. With our prototype, we demonstrate
beam profiling of Gaussian beams over an area of 66.5 microm x 66.5 microm with a
resolution of 0.8 microm (compare with the CMOS pixel size of 10 microm). The
resolution can be improved into the range of submicrometers by fabricating
smaller apertures. The good correspondence between the measured and calculated
beam profiles proves the fidelity of our new beam profiling scheme.
PMID- 17041669
TI - Tunable two-dimensional hexagonal phase array in domain-engineered Z-cut lithium
niobate crystal.
AB - An optical phase array with tunable phase step is demonstrated. The phase array
consists of a two-dimensional hexagonal lattice of inverted ferroelectric domains
fabricated on a Z-cut lithium niobate substrate. The electro-optically tunable
phase step is obtained by the application of an external electric field along the
z axis of the crystal via transparent electrodes. Theoretical analysis and
experimental results are presented, showing that a tunable and flexible adaptive
optical illuminator device can be realized by combining the electro-optic
tunability with the Talbot effect. Generation of a multiplicity of light patterns
is shown.
PMID- 17041670
TI - Optical detection of the Casimir force between macroscopic objects.
AB - We report the optical detection of mechanical deformation of a macroscopic object
induced by the Casimir force. An adaptive holographic interferometer based on a
photorefractive BaTiO3:Co crystal was used to measure periodical nonlinear
deformations of a thin pellicle caused by an oscillating Casimir force. A
reasonable agreement between the experimental and calculated values of the first
and second harmonics of the Casimir force oscillations has been obtained.
PMID- 17041672
TI - Giant enhancement of band edge emission in ZnO and SnO nanocomposites.
AB - ZnO/SnO nanocomposites have been designed to enhance the band edge emission and
suppress the defect emission of ZnO nanorods simultaneously. It is found that the
intensity ratio between the band edge and defect emission can be improved by up
to 4 orders of magnitude. The underlying mechanism is interpreted in terms of
surface modification as well as carrier transfer from SnO nanoparticles to ZnO
nanorods. Our approach is very useful for creating highly efficient
optoelectronic devices.
PMID- 17041671
TI - CO and CO2 spectroscopy using a 60 nm broadband tunable MEMS-VCSEL at
approximately 1.55 microm.
AB - The spectroscopic application of a new broadband microelectromechanical-system
tunable vertical cavity surface-emitting laser with single-mode coverage of 60 nm
(245 cm(-1)) in a single, continuous sweep is described. The operation of the
device is illustrated with high-resolution spectra of CO and CO2 over 110 cm(-1)
(27 nm) and 67 cm(-1) (17 nm), respectively, with the CO band shown for high
pressure scans between 1 and 3 bars (0.1-0.3 MPa). The achieved tuning range
opens up new opportunities for tunable diode laser absorption spectroscopy. The
spectra were compared with HITRAN-derived model calculations. The benefits of a
sensor based on this laser are greater speed, laser power, and tuning range.
PMID- 17041673
TI - Sensitive femtosecond coherent anti-Stokes Raman spectroscopy discrimination
between dipicolinic acid and dinicotinic acid.
AB - We demonstrate that femtosecond ultraviolet and visible coherent anti-Stokes
Raman spectroscopy provides the sensitivity and specificity needed to distinguish
between two similar molecules of pyridinedicarboxylic acid. The Fourier
transforms of the temporal measurements provide the energy difference between the
ground state vibrational modes. Quantum chemical calculations provide theoretical
predictions that agree well with the measurements. The present technique allows
us to distinguish 10 cm(-1) frequency shifts by using pulses ten times broader
than the shifts.
PMID- 17041674
TI - Continuous-wave frequency comb Fourier transform source based on a high
dispersion cavity.
AB - A dispersive grating compressor was included in a fiber ring laser to generate an
unequally spaced frequency comb spanning approximately 1549-1552 nm. Beating of
nearby modes in the comb naturally assigns unique amplitude modulation
frequencies to each spectral component emitted. The source contains no moving
parts. The single-mode fiber-coupled output is directed through hydrogen cyanide
gas and detected by a photodiode. A Fourier transform of a 1 ms record yields a
spectrum that agrees with results from a grating spectrometer at 0.06 nm
resolution. By engineering stable, broadband combs, the technique could result in
a universal and simple approach for spectroscopy at almost arbitrary measurement
speeds and spectral resolutions limited only by Fourier principles.
PMID- 17041675
TI - Spectral line-shape measurement of an extremely weak amplitude-fluctuating light
source by photon-counting-based second-order correlation spectroscopy.
AB - We demonstrate line-shape measurement of an extremely weak amplitude-fluctuating
light source by using photon-counting-based second-order correlation spectroscopy
combined with the heterodyne technique. The amplitude fluctuation of a finite
bandwidth introduces a low-lying spectral structure in the line shape, and thus
its effect can be isolated from that of the phase fluctuation. Our technique
provides extreme sensitivity suited for single-atom-level applications.
PMID- 17041676
TI - Generation of 11 fs pulses by using hollow-core gas-filled fibers at a 100 kHz
repetition rate.
AB - Using self-phase modulation in a hollow-core fiber filled with xenon, we were
able to produce 2.3 microJ laser pulses with a duration of 10.9 fs at a
repetition rate of up to 100 kHz. We started with 45 fs, 4.4 microJ, 800 nm
pulses generated by a Coherent RegA Ti:sapphire regenerative amplifier system,
then spectrally broadened the 30 nm bandwidth to more than 100 nm. Dispersion
compensation was achieved with two pairs of chirped mirrors. This is believed to
be the first time this type of compression was achieved at a repetition rate as
high as 100 kHz. This brings the advantages of few-cycle laser pulses to
experiments that require high-repetition-rate, low-energy laser systems, for
example, coincidence experiments.
PMID- 17041677
TI - Generating single attosecond pulses via spatial filtering.
AB - The first observation of isolated attosecond pulses by Hentschel [Nature 414, 509
(2001)] resulted from an experiment that left the exact mechanism of their
generation unresolved. A complete simulation of the experiment reveals the reason
for its success: single pulses were efficiently isolated from two or more
generated pulses by spatial filtering in the far field. Our explanation suggests
a new, simple paradigm for the production of isolated attosecond bursts. We show
that this method can be used, in conjunction with carrier-envelope phase
stabilization, to select single attosecond pulses by use of 10 fs driving pulses.
PMID- 17041678
TI - Propagation of femtosecond pulses in large-mode-area, higher-order-mode fiber.
AB - We demonstrate propagation of 14 nJ femtosecond pulses through a large-mode-area,
higher-order-mode (HOM) fiber with an effective area of 2100 microm2. The pulses
propagate stably in the LP07 mode of the fiber through lengths as long as 12 m.
The strongly chirped pulses exiting the amplifier fiber are dechirped by the high
order-mode fiber, resulting in pulses with a peak power of 61 kW after
propagation in 5 m of the positive-dispersion fiber. A small amount of self-phase
modulation is observed in the compressed pulses and is described well by a
nonlinear Schrodinger equation model that takes into account the measured
effective area and dispersion of the HOM fiber.
PMID- 17041679
TI - Crystal optics as guard apertures for coherent x-ray diffraction imaging.
AB - A crucial issue in coherent x-ray diffraction imaging experiments is how to
increase the signal-to-noise ratio when measuring relatively weak diffraction
intensities from a nonperiodic object. A novel crystal guard aperture is
described that makes use of a pair of multiple-bounce crystal optics to eliminate
unwanted parasitic scattering background. This background is often produced by
upstream optical elements such as a coherent-beam defining aperture. Recent
experimental observation and theoretical analysis confirm the effectiveness of
the crystal guard aperture method with coherence-preserved wave propagation
through the crystal guard aperture and dramatically reduced scattering background
in coherent x-ray diffraction images.
PMID- 17041680
TI - What do practitioners think? A qualitative study of a shared care mental health
and nutrition primary care program.
AB - OBJECTIVE: To develop an in-depth understanding of a shared care model from
primary mental health and nutrition care practitioners with a focus on program
goals, strengths, challenges and target population benefits. DESIGN: Qualitative
method of focus groups. SETTING/PARTICIPANTS: The study involved fifty-three
practitioners from the Hamilton Health Service Organization Mental Health and
Nutrition Program located in Hamilton, Ontario, Canada. METHOD: Six focus groups
were conducted to obtain the perspective of practitioners belonging to various
disciplines or health care teams. A qualitative approach using both an editing
and template organization styles was taken followed by a basic content analysis.
MAIN FINDINGS: Themes revealed accessibility, interdisciplinary care, and complex
care as the main goals of the program. Major program strengths included
flexibility, communication/collaboration, educational opportunities, access to
patient information, continuity of care, and maintenance of practitioner and
patient satisfaction. Shared care was described as highly dependent on
communication style, skill and expertise, availability, and attitudes toward
shared care. Time constraint with respect to collaboration was noted as the main
challenge. CONCLUSION: Despite some challenges and variability among practices,
the program was perceived as providing better patient care by the most
appropriate practitioner in an accessible and comfortable setting.
PMID- 17041681
TI - Of clamps, clips, and computers.
PMID- 17041682
TI - Myotrophin/V-1 does not act as an extracellular signal to induce myocyte
hypertrophy.
AB - The myotrophin/V-1 protein was originally found to be elevated in failing heart
tissues and was described as an exogenously acting hypertrophy-inducing factor.
However, several studies have proposed only intracellular functions for this
protein. We investigated whether this protein is an exogenously acting
hypertrophy-inducing trophin or an intracellular nuclear factor of kappa B
(NFkappaB) regulatory protein. In the current report, immunofluorescence and cell
fractionation studies showed that myotrophin is present only in the cytoplasm and
is not actively released into the extracellular environment in response to
hypertrophy-inducing stimuli. Moreover, in response to ischemia/reperfusion
injury, an active release of myotrophin from adult rat myocardium was not
observed. Furthermore, protein synthesis studies in rat neonatal myocytes
indicated that exogenous myotrophin did not induce hypertrophy. On the other
hand, myotrophin stimulates the generation of NFkappaB dimers in vitro and thus
regulates the NFkappaB-mediated transcription in cardiac myocytes. Taken
together, these studies suggest that myotrophin is a strictly cytosolic protein
that regulates the NFkappaB-mediated transcriptional process.
PMID- 17041683
TI - A simple and fast experimental model of myocardial infarction in the mouse.
AB - In this report, we describe a simple and fast method for creating a murine
myocardial infarction model and providing a useful and convenient tool for the
research in ischemic heart disease. We established acute myocardial infarction in
the Kunming-strain mouse within 2 minutes by ligating the left anterior
descending coronary artery. The model was evaluated by observing the changes in
histology and in the serum levels of aspartate aminotransferase and lactate
dehydrogenase. Obvious myocardial necrosis was found in the 24-hr experimental
(ligation) group. The average size of the infarction was 44.3% +/- 2.9% of the
left ventricle. Serum levels of aspartate aminotransferase and lactate
dehydrogenase reached their peak in the 24-hr experimental group and were normal
in the 72-hr experimental group. We set forth a simple and quick method for
producing acute myocardial infarction experimentally in the mouse. The model can
be reproduced in a stable manner, under experimental conditions that are easy to
duplicate.
PMID- 17041684
TI - Nitric oxide, endothelin-1, and superoxide production in arterial bypass grafts.
AB - In this study, basal and thrombin-stimulated release of nitric oxide and
endothelin-1 in the internal mammary artery and the radial artery were measured,
together with superoxide radicals generated after anoxia and reoxygenation.
Arterial segments were obtained from patients undergoing coronary bypass
operations. Quantification of nitric oxide was performed by measuring the stable
oxidation products of nitric oxide. Endothelin levels were measured by an enzyme
immunoassay kit, and the superoxides were measured by lucigenin-enhanced
chemiluminescence. Basal and stimulated release of nitric oxide from the internal
mammary artery is significantly higher than that in the radial artery. On the
other hand, basal release of endothelin-1 is less in the internal mammary artery
than in the radial artery, but similar after stimulation. In our study, the
quantity of superoxide radicals produced by the internal mammary artery was
greater than that produced by the radial artery. Our results show that there are
differences between these 2 arteries in regard to production of nitric oxide,
endothelin-1, and superoxide radicals. These differences may have a role in the
process of atherogenesis and may contribute to long-term patency of arterial
bypass grafts. These results may also explain the mechanism of radial artery
graft spasm in coronary artery surgery and may constitute a basis for future
pharmacological and clinical improvements for successful surgical application.
PMID- 17041685
TI - Lowest hematocrit on cardiopulmonary bypass impairs the outcome in coronary
surgery: An Italian Multicenter Study from the National Cardioanesthesia
Database.
AB - Severe hemodilutional anemia on cardiopulmonary bypass increases morbidity and
mortality after coronary surgery. The present study focuses on the lowest
hematocrit values during extracorporeal circulation and on allogenic blood
transfusions as mortality and morbidity risk factors. The records of 1,766
consecutive adult patients undergoing isolated coronary artery bypass graft
surgery at 3 institutions have been analyzed retrospectively for in-hospital
mortality and adverse outcomes. Clinical data were from the Italian National
Cardioanesthesia Database. Multivariate analysis and analysis of receiver
operating characteristic curves were applied. The lowest hematocrit value on
cardiopulmonary bypass was an independent risk factor for postoperative low
output syndrome and renal failure. The hematocrit cutoff values were similar for
renal failure (23%) and low-output syndrome (24%). Blood transfusions were
significantly associated with both renal failure and low-output syndrome. The
risk of renal failure doubled when the nadir-on-cardiopulmonary-bypass hematocrit
occurred in transfused patients. Anemia upon cardiopulmonary bypass was not
associated with death. Our findings confirm that both severe anemia and blood
transfusions were significantly associated with renal failure and low-output
syndrome.
PMID- 17041686
TI - Open-chest management after heart transplantation.
AB - Postcardiotomy open-chest management has been widely used in cardiac surgery.
Although this strategy can be applied to heart transplantation, the use of
immunosuppressants in transplant recipients raises particular concerns about
sternal wound infection and impaired healing. We performed a retrospective review
of 403 patients who had undergone 410 heart transplantations at our institution
from 1985 through 2004. Among them, 9 patients (2.2%) had open-chest management
postoperatively. There were 8 men and 1 woman, with a mean age of 58 +/- 7 years.
The graft ischemic time ranged from 130 to 374 minutes (mean, 218 +/- 99 min),
and the cardiopulmonary bypass time ranged from 98 to 360 minutes (mean, 210 +/-
69 min). In all cases, the reason for open-chest management was hemodynamic
lability that precluded chest closure after transplantation. One patient also
experienced postoperative bleeding. All patients underwent delayed sternal
closure between postoperative days 1 and 11 (median, 4 days). Delayed sternal
closure did not cause any significant hemodynamic changes. One patient died of
stroke on postoperative day 22. No patient had sternal wound infection or
impaired wound healing during the follow-up period. We conclude that, when
required, open-chest management is an effective and safe measure for
hemodynamically unstable heart transplant patients.
PMID- 17041687
TI - Direct versus side-graft cannulation of the right axillary artery for antegrade
cerebral perfusion.
AB - Antegrade selective cerebral perfusion through the right axillary artery has
proved to be a safe and effective method for cerebral protection in aortic
surgery. In this study, we prospectively evaluated the techniques of direct right
axillary artery cannulation (Group 1) and right axillary artery side-graft
cannulation (Group 2), investigated cannulation-related complications, and
determined the hemodynamic advantages and disadvantages of both cannulation
techniques. Sixty-eight patients underwent surgery from April 2001 through August
2004 with the diagnoses of ascending and aortic arch aneurysms (10 patients),
type A aortic dissection (56 patients), and aortic pseudoaneurysm (2 patients).
There were 22 patients in Group 1 (33.4%) and 46 patients in Group 2 (67.6%). The
antegrade selective cerebral perfusion flow was 500 to 700 mL/min in Group 1,
whereas in Group 2 the flow was adjusted in accordance with the mean right radial
arterial pressure, which was 50 mmHg. There was no significant difference between
the groups in antegrade selective cerebral perfusion times, but the transient
neurologic dysfunction rate (4 of 22 patients in Group 1 vs 1 of 42 in Group 2)
was significantly lower in Group 2 (P =0.035). In Group 1, axillary artery
dissection occurred in 2 patients (9%), and postoperative arm ischemia occurred
in 1 patient (4.5%). These complications were not seen in Group 2 (P =0.031). The
side-graft cannulation technique may be more acceptable because of its lower
local-complication rate and because it provides pressure-controlled cerebral
perfusion.
PMID- 17041688
TI - The transition from open to endoscopic saphenous vein harvesting and its clinical
impact: The Texas Heart Institute experience.
AB - Open saphenous vein harvesting can be associated with wound complications,
incision pain, prolonged convalescence, and poor cosmetic results. Endoscopic
vein harvesting has been widely used for prevention of these problems. We
compared outcomes of open and endoscopic vein harvesting for coronary artery
bypass grafting at the Texas Heart Institute. We retrospectively analyzed data
from 1,573 consecutive coronary artery bypass procedures performed at our
institution during a 20-month period. Each procedure included saphenectomy by
endoscopic vein harvesting (n = 588) performed by physician assistants, or by
traditional open vein harvesting (n = 985) performed by physicians or physician
assistants. The primary outcome variable was the incidence of postoperative leg
infections. Both groups were similar in terms of preoperative risk factors. After
surgery, leg wound infections were significantly less frequent in the endoscopic
vein harvesting group (3/588, 0.5%) than in the open vein harvesting group
(27/985, 2.7%; P < 0.002). The most common organism involved in leg infections
was Staphylococcus (20/30, 66%): S. aureus was present in 14 of 30 infections
(47%). Open vein harvesting was the only significant independent risk factor for
leg infection. We conclude that endoscopic vein harvesting reduces leg wound
infections, is safe and reliable, and should be the standard of care when venous
conduits are required for coronary artery bypass grafting and vascular
procedures. Although the transition from open to endoscopic vein harvesting can
be challenging in institutions, it can be successful if operators receive
adequate training in endoscopic technique and are supported by surgeons and
staff.
PMID- 17041689
TI - Myocardial injury in coronary artery bypass grafting: On-pump versus off-pump
comparison by measuring heart-type fatty-acid-binding protein release.
AB - This prospective study uses heart-type fatty-acid-binding protein (hFABP) and
creatine kinase-MB (CK-MB) release to compare myocardial injury in on-pump versus
off-pump coronary artery bypass grafting (CABG). Fifty patients were randomly
assigned to on-pump or off-pump CABG. The hFABP and CK-MB concentrations were
measured in serial venous blood samples drawn before heparinization in both
groups and after aortic unclamping at 1, 2, 4, 8, 24, 48, and 72 hours in the on
pump group. In the off-pump group, samples were taken after the last distal
anastomosis at the same time intervals as in the on-pump group. The total amount
of hFABP and CK-MB released was significantly higher in the on-pump than in the
off-pump group (hFABP = 100.43 +/- 77.63 vs 3.94 +/- 0.36 ng/mL, P < 0.0001; CK
MB = 33.33 +/- 3.81 vs 28.65 +/- 3.91 log units, P < 0.001). In all patients,
hFABP levels peaked as early as 1 hour after declamping (on-pump group) or 2
hours after the last distal anastomosis (off-pump group), whereas CK-MB peaked
only at 4 hours after declamping (on-pump group) or 24 hours after the last
distal anastomosis (off-pump group). The lower release of hFABP and CK-MB in the
off-pump CABG group indicates that on-pump CABG with cardioplegic arrest causes
more myocardial damage than does off-pump CABG. Heart-type fatty-acid-binding
protein is a more rapid marker of perioperative myocardial damage, peaks earlier
than CK-MB, and may predict the requirement for intensive monitoring for
postoperative myocardial infarction.
PMID- 17041690
TI - Experience with the Edwards MIRA mechanical bileaflet valve in the aortic and
mitral positions.
AB - The Edwards MIRA bileaflet mechanical prosthesis, a heart valve not yet available
in the United States, is designed with a unique hinge mechanism, curved leaflets,
and thin titanium housing. We performed this study to investigate its clinical
performance and postoperative hemodynamic results. We implanted 58 Edwards MIRA
prostheses in 51 patients in the aortic (n = 18), mitral (n = 26), and aortic and
mitral (n = 7) positions. Patients' ages ranged from 25 to 84 years (mean age,
53.7 +/- 13.6). Operative mortality was 2% (n = 1), and late mortality was 4% (n
= 2). Thromboembolic events were observed in 2 patients (valve thrombosis in 1
and a cerebrovascular event in 1). There were no complications related to
anticoagulation. No signs of valvular dysfunction or paravalvular leakage were
observed. Peak transvalvular gradients of the aortic prostheses ranged from 24.25
+/- 5.32 mmHg for the 21-mm valve to 11 +/- 1.41 mmHg for the 25-mm valve. The
effective orifice area ranged from 1.99 +/- 0.12 cm2 for the 21-mm valve to 2.44
+/- 0.17 cm2 for the 25-mm valve. The mean transvalvular gradients of the mitral
prostheses ranged from 5.85 +/- 2.91 mmHg for the 27-mm valve to 4.5 +/- 0 mmHg
for the 31-mm valve. The effective orifice area ranged from 2.31 +/- 0.03 cm2 for
the 27-mm valve to 2.64 +/- 0.05 cm2 for the 33-mm valve. These preliminary data
suggest good hemodynamic function and a low rate of valve-related complications
in the use of the Edwards MIRA mechanical prosthesis.
PMID- 17041691
TI - Surgical treatment of cardiac hydatid disease: A report of 7 cases.
AB - Cardiac echinococcosis is a rare but potentially very serious complication of
hydatid disease. It is a diagnostic and therapeutic challenge due to the
variability of signs and symptoms at presentation and to its numerous, often
unpredictable, preoperative complications. Our clinical experiences with 7 cases
of cardiac echinococcosis are reported, and the diagnostic and therapeutic
considerations for the management of patients are discussed, together with a
review of the literature.
PMID- 17041694
TI - Cannulation in the diseased aorta: a safe approach using the Seldinger technique.
AB - The Seldinger technique is a method of femoral cannulation that has been used to
establish cardiopulmonary bypass. Reports of cannulation of the ascending aorta
for antegrade perfusion using the Seldinger method are anecdotal. To the best of
our knowledge, the approach described herein for direct cannulation of the
ascending aorta with use of the Seldinger technique for antegrade perfusion has
not been previously described in the English-language medical literature. This
method is helpful when the surgeon is treating a patient who has a calcified
ascending aorta, complicated aortic dissection, calcified femoral vessels, or a
diseased thoracoabdominal aorta. In such cases, retrograde perfusion has been
associated with severe complications as a result of atheromatous embolization
from the descending thoracic aorta. Herein, we describe our approach to
cannulation for cardiopulmonary bypass, which entails insertion of an aortic
cannula into the ascending aorta by means of the Seldinger technique. A soft-tip
guidewire is inserted through an arterial entry catheter that has been used to
puncture a hole in the wall of the vessel. Then the aortic cannula is introduced
into the vessel, sliding along the guidewire. Guided by transesophageal
echocardiography, the tip of the cannula is positioned carefully and is then
advanced into the descending aorta. This positioning of the cannula decreases the
chance of arterial embolization, thereby improving cerebral protection. If
cannulation of the ascending aorta is not feasible, the transverse aortic arch or
proximal descending aorta can be used.
PMID- 17041692
TI - The cardiomyopathy of iron deficiency.
AB - Iron-deficiency anemia can have deleterious effects on the heart. Herein, we
describe the effects of iron deficiency on the heart as corroborated with
electrocardiography, radiology, echocardiography, and cardiac catheterization. We
review the pathophysiology, clinical features, and management of iron-deficiency
induced cardiomyopathy.
PMID- 17041693
TI - The open-artery hypothesis revisited.
PMID- 17041695
TI - Alternative surgical strategy for the treatment of a mycotic aortic arch
aneurysm.
AB - We report the case of a 69-year-old man who presented with a symptomatic mycotic
aneurysm of the aortic arch. Diagnosis was confirmed by positron emission
tomography and by blood cultures positive for Salmonella species. A complete
resection of the aortic arch process was performed via left thoracotomy using a
cryopreserved aortic homograft and normothermic left heart bypass. The left-sided
cerebral vessels were clamped, and adequacy of collateral left brain flow and
oxygenation was confirmed by neurophysiologic monitoring. Using this less
invasive operative strategy, we avoided the risks inherent to deep hypothermic
circulatory arrest and the use of prosthetic materials.
PMID- 17041696
TI - Catheterization of the AbioCor implantable replacement heart: evaluation of the
unique physiology created by the device.
AB - We performed the 1st catheterization of an AbioCor implantable replacement heart,
in a patient who had developed high right-sided pump pressures, to determine
whether the high pressures were caused by graft kinking or obstruction.
PMID- 17041697
TI - Clinical presentation of persistent 5th aortic arch: 3 new cases.
AB - We report 3 cases of a persistent 5th aortic arch. This anomaly is usually
associated with other intracardiac defects. Although all 3 patients were found to
have similar vascular structures that were best explained by the persistence of
the 5th aortic arch into postnatal life, the clinical presentations were quite
different. One patient presented with coarctation of the aorta, the 2nd patient
with cyanosis, and the 3rd patient with pulmonary overcirculation. The 2nd case
is unique in that the 5th aortic arch was found to be sensitive to prostaglandin
E1. Understanding the embryologic derivation and differing presentations of a
persistent 5th aortic arch aids in diagnosis and management of these patients.
PMID- 17041698
TI - Successful transcatheter coil occlusion of a right-sided patent ductus arteriosus
with aberrant left subclavian artery.
AB - Right aortic arch is a relatively rare congenital anomaly. The combination of a
right aortic arch, a right patent ductus arteriosus, and an aberrant left
subclavian artery in a child with an otherwise structurally normal heart is very
uncommon. We report the successful transcatheter coil occlusion of a right-sided
patent ductus arteriosus in a child with the above-mentioned anatomy. To our
knowledge, such a case has not been reported in the English-language medical
literature to date.
PMID- 17041699
TI - Chronic pseudoaneurysm and coarctation of the aorta: a rare delayed complication
of trauma.
AB - We report an unusual case of pseudoaneurysm and coarctation of the descending
thoracic aorta after trauma. The coarctation of aorta resulted in hypertension,
severe left ventricular dysfunction, and symptoms of congestive heart failure.
Surgical bypass resulted in control of blood pressure and improvement of heart
failure symptoms. The mechanism of aortic injury leading to the development of
this rare combination is discussed.
PMID- 17041700
TI - Endoluminal stenting of mycotic saccular aneurysm at the aortic arch.
AB - Endovascular grafts have been widely used for the treatment of aneurysms since
the early 1990s. They are preferred especially for use in patients in whom
conventional surgical methods carry high risks of death and morbidity. Increasing
operator experience and technical refinements in endovascular grafting have
enabled these procedures to be performed even in critical segments of the aorta,
such as the thoracic and arch levels. In this report, we present the case of a
patient who was treated successfully with an endovascular graft for a mycotic
saccular aneurysm located just below the left subclavian artery.
PMID- 17041701
TI - Nonsurgical management of left main coronary artery aneurysms: report of 2 cases
and review of the literature.
AB - Aneurysms of the left main coronary artery are exceedingly rare clinical
entities, encountered incidentally in approximately 0.1% of patients who undergo
routine angiography. Thrombosis within the aneurysm can lead to distal
embolization and myocardial infarction. These lesions can extend into adjacent
coronary branches and can occur in the presence or absence of obstructive
coronary disease. Depending on the severity of coexistent coronary stenoses,
patients with left main coronary artery aneurysms can be effectively managed
either operatively or medically. We report the cases of 2 patients who were
treated medically for large left main coronary aneurysms and concomitant right
coronary artery ectasia.
PMID- 17041702
TI - Daughter, you broke my heart: accidental thrombosis at a muscular bridge.
AB - We report the case of a 59-year-old trained runner, who sustained an acute
myocardial infarction, with residual effort angina, following extreme exertion
while experiencing severe anxiety. Coronary angiography revealed that this
patient had a myocardial bridge at the mid-left anterior descending artery, and
an occlusive clot had developed at the proximal end of the muscular bridge. We
discuss the possible relationships between the various circumstances of this
sudden event. We argue that, under exceptional conditions, myocardial bridges can
lead to myocardial infarction by clot formation.
PMID- 17041703
TI - Transcatheter treatment of "pulmonary artery hypertension" due to patent ductus
arteriosus and pulmonary artery stenosis.
AB - The association between large, left-sided patent ductus arteriosus and severe,
peripheral, right pulmonary artery stenosis with no other cardiac malformation is
an unreported condition that might be misdiagnosed as pulmonary hypertension due
to long-standing ductal shunt. A 57-year-old man with supposed hypertensive
patent ductus arteriosus underwent confirmatory cardiac catheterization. At
angiography, a severe pre-hilar right pulmonary artery stenosis (peak pressure
gradient, 65 mmHg) was found to complicate the hemodynamic picture of a moderate
to-large patent ductus arteriosus (QP/QS, 1.7:1), by causing pulmonary
hypertension (mean pressure, 65 mmHg) and left-to-right pulmonary flow imbalance.
Both lesions were treated in a single procedure of right pulmonary artery
stenting and patent ductus arteriosus closure, after which the pulmonary artery
pressure significantly decreased (mean, 35 mmHg). In our opinion, a thorough
hemodynamic evaluation followed by pulmonary angiography should be mandatory
before proceeding to patent ductus arteriosus closure in the adult patient who
has "hypertensive" ductus, in whom possible associated malformations can be
missed due to a poor echocardiographic window.
PMID- 17041705
TI - Giant left atrium with rheumatic mitral stenosis.
AB - A chest radiograph of a 38-year-old woman, who was diagnosed with rheumatic
mitral stenosis, revealed cardiac enlargement due to a giant left atrium that was
distorting the cardiac structures. The patient's cardiothoracic ratio was
approximately 0.90. A giant left atrium can readily be delineated by
echocardiography. Optimal timing of surgery is important in cases of mitral
stenosis, because delaying mitral valve replacement can lead to fatal outcomes.
To our knowledge, the left atrial diameter of 18.7 cm that we found in our
patient is the largest reported to date.
PMID- 17041704
TI - Arrhythmogenic right ventricular dysplasia: initial presentation in a middle-aged
woman.
AB - Arrhythmogenic right ventricular dysplasia is a rare disorder that is familial in
30% to 50% of cases. It is characterized by structural and functional
abnormalities of the right ventricle and a propensity for ventricular arrhythmias
and sudden death. We report the case of a 59-year-old woman who had idiopathic,
severe, right-sided heart failure and nonsustained ventricular tachycardia. She
was diagnosed with arrhythmogenic right ventricular dysplasia by means of cardiac
magnetic resonance imaging. We discuss the clinical features, diagnostic
criteria, and role of cardiac magnetic resonance imaging in the diagnosis of
arrhythmogenic right ventricular dysplasia.
PMID- 17041706
TI - Penetrating trauma to the mitral valve and ventricular septum.
AB - Penetrating cardiac trauma is typically life-threatening and often requires
urgent surgical intervention. Penetrating injury can cause damage in more than 1
cardiac structure that may be difficult to identify at the initial urgent
operation. We describe the case of a young man in whom a perimembranous
ventricular septal defect and perforation of the anterior leaflet of the mitral
valve were caused by a screwdriver wound.
PMID- 17041707
TI - Symptomatic bradycardia due to total occlusion of left circumflex artery without
electrocardiographic evidence of myocardial infarction at initial presentation.
AB - We present the case of a 72-year-old man who was admitted due to low blood
pressure and acute-onset dizziness with sinus bradyarrhythmia on
electrocardiography. He had no obvious anginal symptoms, and there was no marked
evidence of myocardial infarction. He was ultimately diagnosed with coronary
artery disease with total occlusion of the left circumflex coronary artery, and
he underwent successful coronary angioplasty after primary conduction disorders
were ruled out.
PMID- 17041708
TI - Left ventricular outflow tract obstruction after bioprosthetic mitral valve
replacement with posterior mitral leaflet preservation.
AB - We present a case of transient left ventricular outflow tract obstruction after
mitral valve replacement with a high-profile bioprosthesis; only the posterior
native mitral valve leaflet was preserved. A 76-year-old woman was admitted to
our institution with pulmonary edema. Two weeks earlier, she had undergone mitral
valve replacement at our hospital due to severe mitral stenosis and 2+ mitral
regurgitation complicated by cardiac failure and atrial fibrillation. The patient
was taking digoxin, furosemide, and warfarin at the time of readmission.
Echocardiography showed a narrowed left ventricular outflow tract. Doppler
echocardiography revealed a peak 64-mmHg gradient between the septum and the
strut of the bioprosthesis. The patient was successfully treated medically. This
case indicates that the risk of left ventricular outflow tract obstruction after
bioprosthetic mitral valve replacement is not always eliminated by removal of the
anterior mitral valve leaflet when the posterior mitral leaflet is preserved.
PMID- 17041709
TI - Use of a nasal speculum for chest-drain insertion: a simple technique.
AB - Tube thoracostomy is a very commonly performed procedure in cardiothoracic
surgery. Insertion of a chest drain requires expertise to minimize complications.
We describe a simple technique of using a nasal speculum to perform this
procedure.
PMID- 17041710
TI - Nontraumatic pericardiophrenic defect with tamponade.
PMID- 17041711
TI - An unusual course of the ramus intermedius: shown by multislice computed
tomographic coronary angiography.
PMID- 17041712
TI - Apical hypertrophic cardiomyopathy: diagnosed by cardiac magnetic resonance
imaging.
PMID- 17041713
TI - A closed interatrial septal aneurysm mimicking a tumor in the left atrium.
PMID- 17041714
TI - Chimpanzee heart was not rejected by human recipient.
PMID- 17041715
TI - Use of a recirculator device for pericardial cold saline irrigation in cardiac
surgery.
PMID- 17041716
TI - Pharmacologic targets and prototype therapeutics in the kallikrein-kinin system:
bradykinin receptor agonists or antagonists.
AB - The kallikrein-kinin system (KKS) is a complex system produced in various organs.
This system includes kininogen (precursor for kinin), kallikreins, and
pharmacologically active bradykinin (BK), which is considered to be
proinflammatory and/or cardioprotective. It is a proinflammatory polypeptide that
is involved in many pathological conditions and can cause pain, inflammation,
increased vascular permeability, vasodilation, contraction of various smooth
muscles, as well as cell proliferation. On the other hand, it has been shown that
BK has cardioprotective effects, as all components of KKS are located in the
cardiac muscles. Numerous observations have indicated that decreased activity of
this system may lead to cardiovascular diseases, such as hypertension, cardiac
failure, and myocardial infarction. BK acts on two receptors, B1 and B2, which
are linked physiologically through their natural stimuli and their common
participation in a variety of inflammatory responses. Recently, numerous BK
antagonists have been developed in order to treat several diseases that are due
to excessive BK formation. Although BK has many beneficial effects, it has been
recognized to have some undesirable effects that can be reversed with BK
antagonists. In addition, products of this system have multiple interactions with
other important metabolic pathways, such as the renin-angiotensin system.
PMID- 17041717
TI - Infusion of autologous retrodifferentiated stem cells into patients with beta
thalassemia.
AB - Beta-thalassemia is a genetic, red blood cell disorder affecting the beta-globin
chain of the adult hemoglobin gene. This results in excess accumulation of
unpaired alpha-chain gene products leading to reduced red blood cell life span
and the development of severe anemia. Current treatment of this disease involves
regular blood transfusion and adjunct chelation therapy to lower blood
transfusion-induced iron overload. Fetal hemoglobin switching agents have been
proposed to treat genetic blood disorders, such as sickle cell anemia and beta
thalassemia, in an effort to compensate for the dysfunctional form of the beta
globin chain in adult hemoglobin. The rationale behind this approach is to pair
the excess normal alpha-globin chain with the alternative fetal gamma-chain to
promote red blood cell survival and ameliorate the anemia. Reprogramming of
differentiation in intact, mature, adult white blood cells in response to
inclusion of monoclonal antibody CR3/43 has been described. This form of
retrograde development has been termed "retrodifferentiation", with the ability
to re-express a variety of stem cell markers in a heterogeneous population of
white blood cells. This form of reprogramming, or reontogeny, to a more
pluripotent stem cell state ought to recapitulate early hematopoiesis and
facilitate expression of a fetal and/or adult program of hemoglobin synthesis or
regeneration on infusion and subsequent redifferentiation. Herein, the outcome of
infusion of autologous retrodifferentiated stem cells (RSC) into 21 patients with
beta-thalassemia is described. Over 6 months, Infusion of 3-h autologous RSC
subjected to hematopoietic-conducive conditions into patients with beta
thalassemia reduced mean blood transfusion requirement, increased mean fetal
hemoglobin synthesis, and significantly lowered mean serum ferritin. This was
always accompanied by an increase in mean corpuscular volume (MCV), mean
corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration
(MCHC) in such patients. No adverse side effects in response to the infusion of
autologous RSC were noted. This novel clinical procedure may profoundly modify
the devastating course of many genetic disorders in an autologous setting, thus
paving the way to harnessing pluripotency from differentiated cells to regenerate
transiently an otherwise genetically degenerate tissue such as thalassemic blood.
PMID- 17041718
TI - xSyndecan-4 regulates gastrulation and neural tube closure in Xenopus embryos.
PMID- 17041719
TI - The Israeli Rett Syndrome Center. Evaluation and transdisciplinary play-based
assessment.
AB - Rett syndrome (RS) is a neuro-developmental syndrome of genetic origin, which
mainly affects women. Individuals diagnosed with RS exhibit a variety of
functional difficulties, which impair their quality of life. The variety of
impairments and the differences between each child makes it necessary to
administer skilled treatment, individually tailored to each client. Since the
foundation of proper treatment is based on a structured, well administered,
insightful assessment, the individual with RS with her complex array of
difficulties should benefit from such a procedure. This notion has led to the
establishment of the Israel Rett Syndrome Center. The center includes a medical
branch located at the Safra Shildren's Medical Center at Tel Hashomer and an
education/rehabilitation team, who performs assessments in special education
facilities and residential settings throughout Israel. The assessment team works
by means of arena assessment according to the concept of play-based assessment.
This article presents the working model used by the education/rehabilitation team
at the Israeli Rett Syndrome Center. The principles and working characteristics
of the Israel Rett Syndrome Center team are suggested here as a potential model
for establishing additional teams, presenting similar evaluation services for
other individuals with RS as well as for analogous populations.
PMID- 17041720
TI - Physical therapy intervention for individuals with Rett syndrome.
AB - Individuals with Rett syndrome (RS) present a vast array of orthopedic and
neurological difficulties. Typical problems, which may need to be addressed, when
treating this population are functional limitations, low cardiovascular capacity,
hypotonia, ataxia, apraxia, loss of transitional movements, spasticity, scoliosis
and/or kyphosis, loss of ambulation, loss of hand function, foot deformities, and
spatial disorientation. Coping with such difficulties and overcoming the
associated limitations carry a wearisome task for the individual with Rett as
well as for her family. An informed and intensely applied physical therapy regime
can help the child and the family cope and even overcome the above-mentioned
limitations. The present article presents some insights regarding the
intervention with individuals with RS, an overview of typical neuromuscular
problems associated with RS, and appropriate suggestions pertaining to clinical
intervention that have been found to contribute to this population's well-being.
The information presented is mainly based on the clinical knowledge of the
authors.
PMID- 17041721
TI - Effects of caloric restriction and exercise training on skeletal muscle
histochemistry in aging Fischer 344 rats.
AB - The purpose of this study was to determine the effects of calorie restriction and
exercise on hindlimb histochemistry and fiber type in Fischer 344 rats as they
advanced from adulthood through senescence. At 10 months of age, animals were
divided into sedentary fed ad libitum, exercise (18 m/min, 8% grade, 20 min/day,
5 days/week) fed ad libitum, and calorie restricted by alternate days of feeding.
Succinic dehydrogenase, myosin adenosine triphosphatase (mATPase at pH 9.4),
nicotine adenonine dinucleotide reductase, and Periodic Acid Shiff histochemical
stains were performed on plantaris and soleus muscles. The results indicated that
aging resulted in a progressive decline in plantaris Type I muscle fiber in
sedentary animals, while exercise resulted in maintenance of these fibers. The
percent of plantaris Type II fibers increased between 10 and 24 months of age.
Exercise also resulted in a small, but significant, increase in the percentage of
plantaris Type IIa fibers at 24 months of age. The soleus fiber distribution for
Type I fibers was unaffected by increasing age in all groups of animals. The
implications of these results suggest the implementation of exercise as a
lifestyle modification as early as possible.
PMID- 17041722
TI - [Biological effects of toosendanin, an active ingredient of herbal vermifuge in
Chinese traditional medicine].
AB - The fact that the fruit and bark of plant belonging to family Melia could be used
as digestive tract-parasiticide and agricultural insecticide was recorded about
two thousand years ago in ancient China. Toosendanin (TSN, C30H38O11, FW=574), a
triterpenoid derivative, was extracted from the bark of Melia toosendan Sieb. et
Zucc. by Chinese scientists in 1950os and used as an ascarifuge in China instead
of imported sendanin. Studies have demonstrated that TSN possesses special
biological actions as well as considerable various values in scientific research,
clinic medicine and agriculture. The first is that by interfering with
neurotransmitter release by causing an initial facilitation, TSN eventually
blocks synaptic transmission at both the neuromuscular junction and central
synapses. The action might result from TSN-induced Ca(2+)-sensitivity change and
final elimination of transmitter release machinery. The second is that despite
sharing many similar actions with botulinum neurotoxin (BoNT) on blocking
neuromuscular transmission, TSN has a markedly antibotulismic action in vivo and
in vitro: TSN-treatment saves the botulism mice or monkeys from death; TSN
incubation in vitro or TSN-injection in vivo endows neuromuscular junction with a
high tolerance to BoNT. Studies suggest that the antibotulismic action is
achieved by preventing BoNT from approaching its enzymatic substrate, SNARE
protein. The third, in recent years, it is also observed that TSN can induce
differentiation and apoptosis in several cell lines, and suppress proliferation
of various human cancer cells. The TSN-induced differentiation is Ca(2+)
dependent and the mitochondria-dependent apoptosis pathway is involved in the TSN
induced apoptosis. The fourth is that TSN inhibits various K(+) channels and
selectively facilitates Ca(2+) current through L-type Ca(2+) channels and hence
elevates [Ca(2+)](i). The TSN-induced [Ca(2+)](i) increase and overload could be
responsible for the TSN-induced biphasic effect on neurotransmitter release, cell
differentiation, apoptosis as well as the cytotoxicity of TSN.
PMID- 17041723
TI - Postsynaptic calcium pathway contributes to synaptic plasticity between retinal
cones and luminosity-type horizontal cells.
AB - It was previously found that the efficacy of synaptic transmission between
retinal cone systems and luminosity-type horizontal cells (LHCs) was activity
dependent. Repetitive activation of red-cone pathway increased the LHCos
hyperpolarizing response to red light, and the response enhancement was
reversible. In this study, intracellular recording and pharmacological method
were applied to investigate the mechanism(s) underlying red-flickering-induced
response enhancement. Lowering intracellular Ca(2+) in the LHC by intracellular
injection of Ca(2+) chelator EGTA prevented the development of red-flickering
induced response enhancement, which implicates the importance of postsynaptic
calcium signal. The response enhancement could also be eliminated by a potent
antagonist of Ca(2+)-permeable AMPA receptor (CP-AMPAR), which suggests the
possibility that Ca(2+) influx via glutamate-gated calcium channels is related to
the changes of [Ca(2+)](i). Furthermore, the administration of ryanodine or
caffeine also attenuated the phenomenon, which gives evidence that the local
calcium signal caused by intracellular calcium-induced calcium release (CICR) may
be involved. Taken together, our data implicate that postsynaptic CICR and CP
AMPAR are related to the activity-dependent response enhancement.
PMID- 17041724
TI - Forced running enhances neurogenesis in the hippocampal dentate gyrus of adult
rats and improves learning ability.
AB - To investigate the effect of forced running in motor-driven wheel on neurogenesis
in the hippocampal dentate gyrus (DG) of adult rats, 5-bromo-2-deoxyuridine
(BrdU), a thymidine analog was applied to mark cell proliferation. Neuroepthelial
stem cell protein (nestin) expression was used to identify neural stem/precursor
cells. The BrdU- and nestin-positive cells were examined by immunohistochemical
technique. The ability of learning was evaluated by Y-maze test to explore the
functional role of the newborn cells in the DG after forced running. It was found
that the number of BrdU- and nestin-positive cells in the DG in running groups
was significantly increased compared to that in the control group (P<0.05). The
effect of forced running on neurogenesis was intensity-dependent. In addition, an
improvement of learning ability in Y-maze test was observed after forced running.
These findings suggest that forced running in motor-driven wheel could enhance
neurogenesis in the hippocampal DG of adult rats and improve learning ability.
PMID- 17041725
TI - [Overexpression of alpha-synuclein in SH-SY5Y cells partially protected against
oxidative stress induced by rotenone].
AB - Both genetic and environmental factors are involved in the pathogenesis of
Parkinsonos disease (PD). Epidemiological studies showed that environmental
factors shared with the common mechanisms of resulting in alpha-synuclein
aggregation by inhibiting complex I of mitochondria and leading to oxidative
stress. To investigate the relationship between alpha-synuclein and oxidative
stress, we used human dopaminergic SH-SY5Y cells transfected with alpha-synuclein
enhanced green fluorescent protein (EGFP). alpha-synuclein gene expression was
determined by immunocytochemistry and real-time quantitative PCR. Both SH-SY5Y
and alpha-synuclein overexpressed SH-SY5Y (SH-SY5Y/Syn) cells were treated with
various concentrations of rotenone for different time. Cell viability and
oxidative stress were detected by MTT assay and DCF assay. Superoxide dismutase
(SOD) activity was assessed with xanthine peroxidase method. Cell apoptosis was
detected with flow cytometry. Results showed that alpha-synuclein gene was
constantly overexpressed in SH-SY5Y/Syn cells. After treatment with rotenone,
both cell viability and complex I activity in these cells were reduced in a
concentration-dependent manner. Oxidative stress was also found in these cells.
Compared with SH-SY5Y cells, SOD activity in SH-SY5Y/Syn cells was increased
distinctly (P<0.05) and alpha-synuclein significantly attenuated rotenone-induced
cell apoptosis. These results suggest that the alpha-synuclein overexpression in
SH-SY5Y cells has a tendency to partially resist oxidative stress induced by
rotenone and this response may assist cell survival.
PMID- 17041726
TI - [Expression of caveolin-1 protein in the rat brain and its role in the
discrimination learning].
AB - Caveolin-1 (Cav-1) is a marker protein for caveolae, and acts as scaffolding
protein to regulate the activities of signaling molecules. Previous studies
indicate that Cav-1 mainly locates at the base of axonal and dendritic terminals
of mouse primary hippocampal neurons and plays an active role in the regulation
of injury-induced synaptic and terminal remodeling in central nervous system. The
aim of this study was to identify the expression profile of Cav-1 protein in the
brains of rats at different ages and to investigate the role of Cav-1 in Y-maze
bright-dark discrimination learning (BDL). Firstly, the expressions of Cav-1 in
the brains of young (1-month), adult (3-month) and aged (22-month) rats were
observed by Western blot. Higher expression in the hippocampus and lower
expression in the cortex were shown in the adult rats. It was also found that the
score of BDL was related with the expression level of Cav-1. Secondly, using open
field test for spontaneous locomotor activities (SLA) and BDL, the role of Cav-1
in the learning and memory was observed. Compared with that in the control adult
group, the Cav-1 protein expression in the hippocampus and prefrontal cortex of Y
maze trained adult rats significantly increased, while no marked changes in the
cerebellum. These results suggest that Cav-1 protein is involved in BDL and plays
an important role in the plasticity of central nervous system.
PMID- 17041727
TI - Forskolin and 8-cyclopentyltheophylline synergistically facilitate the neuronal
activity in the CA2 area of rat hippocampus via cAMP and non-cAMP cascades.
AB - High level of adenosine A1 receptor-like immunoreactivity has been found in the
CA2/CA3a region of adult rat hippocampus, but its roles in the neuronal activity
or signal propagation in hippocampus and its intracellular cascade remain to be
studied. In this study, we examined the relation between adenosine-3',5'-cyclic
monophosphate (cAMP) cascade and suppression of synaptic transmission by
endogenous adenosine through adenosine A1 receptor in the CA2 area. In transverse
hippocampal slice, maximal electrical stimulation of the hilus region (0.6 mA)
only evoked small population spikes (PSs) in the CA2 area (0.5 mV). In the
presence of forskolin (20 micromol/L), a direct adenylate cyclase activator, PSs
in CA2 were increased to 1.1 mV. When 8-cyclopentyltheophylline (8CPT, 2
micromol/L), an adenosine A1 receptor antagonist, was added in the presence of 20
micromol/L forskolin, PSs with an average amplitude of 4.7 mV were recorded in
the CA2 area, much higher than the sum of the amplitude of PSs in the presence of
forskolin and 8CPT alone. To test whether this synergistic potentiation results
from the additive activation of cAMP cascade, the cAMP content in hippocampal
slices was measured with enzyme immunoassay (EIA). Results showed that 8CPT did
not increase the cAMP content in CA2 with or without forskolin. Co-application of
forskolin and Ro 20-1724, a cAMP-specific phosphodiesterase-IV inhibitor, only
increased PSs in CA2 to 1.3 mV but increased cAMP content by 4.4 times. On the
other hand, co-application of 8CPT and 1, 9-dideoxyforskolin, a forskolin analog
which has no effect on adenylate cyclase, did not mimic the synergistic effect of
8CPT and forskolin on PSs in CA2. These results indicate that up-regulation of
adenylate cyclase activity and inhibition of adenosine A1 receptor activity
synergistically facilitate the neuronal activity in the CA2 area and the effect
of adenosine A1 receptor antagonist is via non-cAMP cascade. These data also
suggest that acting on adenosine A1 receptors, endogenous and extragenous
adenosine/adenosine A1 agonist(s) inhibit neuronal activity through different
pathways.
PMID- 17041728
TI - [Changes of NMDA receptor expression in rat hippocampal formation after
establishment of spatial memory by different training modes].
AB - There is no unambiguous report so far on whether short reinforcing training could
establish stable spatial long-term memory and how the NMDA/NR1 expression in the
hippocampal formation changes after establishment of short- and long-term memory.
In the present study, three spatial memory training modes of Morris water maze
were used: spatial long-term memory training mode (LT group), spatial short-term
memory training mode (ST group) and short reinforcing training mode (SRT group).
The characteristics of those memories established by different training modes
were compared. The immunofluorescence histochemical staining technique was used
to observe the changes of NMDA/NR1 expression in the hippocampal formation in the
three groups. The results showed that, during Morris water maze training, no
significant difference was found in the mean latency and the strategies to the
target between the LT and SRT groups. The examination of the memories following
different trainings indicated that the mean latency and the strategies to the
target as well as the times crossing the target in LT group were not
significantly different from those in SRT group, except that the mean time
remaining in the platform quadrant in LT group was significantly longer than that
in SRT group. In addition, no significant difference in the intensity of NMDA/NR1
immunoreactivity in CA1, CA3 and dentate gyrus of the hippocampal formation was
observed between the control and ST groups or between LT and SRT groups. However,
the intensity of NMDA/NR1 immunoreactivity in CA1 area and dentate gyrus in both
LT and SRT groups was significantly increased as compared with that in ST or the
control groups. These results suggest that the short reinforcing training mode
can establish long-term spatial memory, which is almost the same as that
established by the long-term training mode, and that the increase of NMDA/NR1
expression in CA1 area and dentate gyrus of the hippocampal formation may be one
of the mechanisms of spatial long-term memory formation.
PMID- 17041729
TI - [Effects of sodium salicylate on the expressions of gamma-aminobutyricacid and
glutamate and auditory response properties of the inferior colliculus neurons].
AB - The effects of sodium salicylate (NaSA) on the expressions of gamma
aminobutyricacid (GABA) and glutamate (Glu), and auditory response properties of
the inferior colliculus neurons in mice were studied. Thirty-six Kunming mice
were divided into three groups: control group (saline injection); NaSA group
(NaSA 450 mg/kg, i.p., each day for 15 d); NaSA + lidocaine group (NaSA 450 mg/kg
+ lidocaine 10 mg/kg, i.p., each day for 15 d). The expressions of GABA and Glu
were examined with immunohistochemical method. The intensity-rate function,
intensity-latency function and frequency-tuning curve were determined with
extracellular electrophysiological recording. Results are as follows: (1) The
expression of GABA in the NaSA and NaSA + lidocaine groups decreased remarkably
compared with that in the control group; there was no noticeable difference
between the NaSA and NaSA + lidocaine groups. The expression of Glu in the NaSA
group increased significantly compared with that in the control and NaSA +
lidocaine groups. No difference in the expression of Glu was found between the
control and NaSA + lidocaine groups. (2) In NaSA group, the intensity-rate
function displayed a non-monotonic pattern, rising at low intensity and
descending at high intensity; the tip of frequency-tuning curves became broad
after administration of NaSA. (3) The changes in intensity-rate function and
intensity-latency function were not evident and the tips of the frequency-tuning
curves sharpened in the NaSA + lidocaine group. These results suggest that
administration of NaSA increases the expression of Glu-positive neurons and
reduces that of GABA-positive neurons in the inferior colliculus. NaSA changes
the auditory response properties of the inferior colliculus and lidocaine can
reverse these changes.
PMID- 17041730
TI - [Effects of chloride channel blockers on excitatory junction potentials in smooth
muscle cells of cochlear spiral modiolar artery in guinea pigs].
AB - Chloride channels have been identified in vascular smooth muscle cells (SMCs). It
has been shown that these channels are involved in myogenic tone regulation and
neuromuscular transmission in various vascular beds. However, whether the
chloride channels are responsible for the formation of excitatory junction
potentials (EJPs) of SMCs in the spiral modiolar artery (SMA) remains
unelucidated. In the present study, the effects of chloride channel blockers
(niflumic acid, NFA; indanyloxyacetic acid 94, IAA-94; disodium 4, 4'
diisothiocyanatostilbene-2, 2'-disulfonate, DIDS) on EJP were explored in guinea
pigs, using intracellular recording techniques on acutely isolated SMA. It was
found that EJP was evoked in the majority of the SMCs (75%, n=49) with an
adequate electronic stimulation. The amplitude of the EJP was partially blocked
(30% approximately 80%) by combined application of alpha(1) receptor antagonist
(prazosin) and alpha(2) receptor antagonist (idazoxan) at concentration of up to
1 micromol/L, and P(2x) receptor antagonist (PPADS, 10 approximately 100
micromol/L). NFA (100 micromol/L) could further inhibit the residual EJP in the
presence of alpha(1), alpha(2)-adrenergic and P(2x) receptor antagonists. IAA-94
or DIDS not only inhibited the amplitude but also shortened the duration of EJP.
Decrease of extracellular chloride concentration from 135.6 mmol/L to 60 mmol/L
would enhance EJP. Moreover, IAA-94 (100 micromol/L) and DIDS (200 mumol/L) could
reverse the enhancement of EJP by low extracellular Cl(-). NFA (100 micromol/L)
could also block the residual depolarizations evoked by norepinephrine (NE, 1
approximately 50 micromol/L). Based on these results, it is inferred that NE
could activate a novel adrenoceptor to open the chloride channel on the membrane
of the SMCs, leading to a transmembrane Cl(-) current. This current is involved,
at least partially, in the formation of EJP.
PMID- 17041731
TI - [Hypoxic preconditioning induces endoplasmic reticulum stress-related
cardioprotection mediated by p38 mitogen-activated protein kinase].
AB - Calreticulin (CRT), an important Ca(2+)-binding molecular chaperone in the
endoplasmic reticulum (ER), and caspase-12, a pivotal molecule mediating ER
initiated apoptosis, are involved in the ER stress (ERS). Using primary cultured
neonatal cardiomyocytes, CRT and caspase-12 expression and activation during
hypoxic preconditioning (HPC) and hypoxia/reoxygenation (H/R) were studied to
explore the role of ERS in cardioprotection by HPC. And by using SB203580 and
SP600125 [the specific inhibitors of p38 mitogen-activated protein kinase (MAPK)
and c-Jun N-terminal kinase (JNK)] separately, the role of p38 MAPK in HPC
induced ERS was also detected. Neonatal cardiomyocytes were prepared from Sprague
Dawley rats aged 24 h, and cultured in DMEM medium containing 10% fetal bovine
serum, and then randomly divided into six groups as follows: H/R, HPC+H/R,
SB203580+HPC+H/R, SP600125+HPC+H/R, HPC and control groups. H/R was produced by 2
hour hypoxia/14-hour reoxygenation, and HPC by 20-minute hypoxia/24-hour
reoxygenation. Morphological studies, estimation of lactate dehydrogenase (LDH)
leakage and flow cytometry were employed to assess cell apoptosis and necrosis.
CRT and caspase-12 expression and activation, levels of phospho-p38 MAPK and
phospho-JNK were detected by Western blot. All experiments were repeated at least
four separate times. The results obtained are as follows: (1) HPC relieved the
cell injury caused by H/R. Compared with that in H/R group, cellso survival rate
in HPC+H/R group increased by 6.4%, and the apoptosis rate and LDH leakage in the
cell culture medium decreased by 6.6% and 70.0%, respectively. (2) H/R induced
caspase-12 activation (33.2-fold increase in comparison with control) and CRT
expression (8.1-fold increase in comparison with control). HPC itself resulted in
mild CRT up-regulation (2.6-fold increase in comparison with control), but the
extent of up-regulation was lower than that induced by H/R. HPC before H/R was
found to relieve the over-expression of CRT induced by H/R (72.4% decrease), and
to inhibit the activation of caspase-12 (59.6% decrease). (3) The protection of
HPC and HPC-induced up-expression of CRT and inhibition of caspase-12 activation
were almost eliminated when the inhibitor of p38 MAPK, not of JNK, was present
before HPC. These results suggest that HPC protects the neonatal cardiomyocytes
from severe ERS-induced apoptosis during sustained H/R through pre-invoking
proper ERS response. Mild up-expression of CRT and inhibition of caspase-12
activation induced by HPC, which are important protection factors, are mediated
by p38 MAPK, not by JNK.
PMID- 17041732
TI - [Calcium-dependent chloride channels in plasma membrane of oocytes from toad,
Bufo bufo gargarizans].
AB - In this paper, membrane current properties of the fully-grown oocytes from toad,
Bufo bufo gargarizans, were studied by using two-microelectrode voltage clamp
technique. Axion of adult female toad was destroyed, and then ovarian lobes
containing oocytes in stage I to VI were removed and incubated in Ca(2+)-free
ND96 solution with collagenase (1.5 mg/ml) for 1 h. Subsequently, the oocytes
were washed in Ca(2+)-free ND96 solution for 10 min to completely remove the
follicular layer. For the experiments only the oocytes in stage V and VI were
selected and used during 1 to 5 d. The membrane was depolarized from a holding
potential of -80 mV to +60 mV in 10 mV step. It was found that a sustained
outward current was elicited by depolarization. Potassium channel blockers
(tetraethylammonium chloride, TEA, 10 mmol/L and 4-aminopyridine, 4-AP, 10
mmol/L) reduced the outward current to (23.4+/-0.72)% of the maximum. However,
further addition of chloride channel blocker (5-nitro-2, 3-phenypropylamino
benzoate, NPPB, 30 micromol/L) could almost completely block the outward current
to (2.1+/-0.08)% of the maximum. In the presence of TEA and 4-AP, removal of
extracellular Ca(2+) or adding verapamil (40 micromol/L), could also reduce the
outward current to (2.2+/-0.04) % and (3.1+/-0.15) % of the maximum,
respectively. It is concluded that calcium-dependent chloride channels exist in
plasma membrane of Bufo bufo gargarizans oocytes, besides potassium channels.
PMID- 17041733
TI - [Electrophysiological study on rat conduit pulmonary artery smooth muscle cells
under normoxia and acute hypoxia].
AB - The present study was designed to investigate the electrophysiological
characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and
the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the
conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were
divided into acute hypoxia preconditioned group and normoxia group. Hypoxia
solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min
before cell perfusion. Potassium currents were compared between these two groups
using whole-cell patch clamp technique. The total outward current of PASMCs was
measured under normoxia condition when iBTX [specific blocking agent of large
conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent
of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath
solution. PASMCs were classified into three types according to their size, shape
and electrophysiological characteristics. Type I cells are the smallest with
spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show
the biggest size with banana-like appearance. Type III cells have the similar
size with type I, and present intermediary shape between type I and type II. iBTX
had little effect on the total outward current in type I cells, while 4-AP almost
completely blocked it. Most of the total outward current in type II cells was
inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells,
the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia
reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/
33.6) pA for type I cells (P<0.01); (438.3+/-42.8) pA to (277.5+/-44.7) pA for
type II cells (P<0.01); (1 042.0+/-37.2) pA to (613.6+/-23.8) pA for type III
(P<0.01), and raised the resting membrane potentials (E(m)) in all these three
types of cells: (-41.6+/-1.6) mV to (-18.6+/-1.5) mV (P<0.01), (-42.3+/-3.8) mV
to (-30.6+/-3.0) mV (P<0.01), (-43.3+/-1.6) mV to (-28.4+/-1.4) mV (P<0.01), for
type I, II, III cells, respectively. These results suggest that acute hypoxia
suppresses the potassium current and improves the E(m) in PASMCs. These effects
may be involved in the modulation of constriction/relaxation of conduit artery
under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these
three types of PASMCs might account for their different constriction/relaxation
response to acute hypoxia.
PMID- 17041734
TI - Carbon monoxide inhalation protects lung from lipopolysaccharide-induced injury
in rat.
AB - Carbon monoxide (CO), a metabolite of heme catalysis by heme oxygenase (HO), has
been proposed to have anti-oxidative, anti-inflammatory and anti-apoptotic
functions. Lipopolysaccharide (LPS)-induced lung injury (LI) is characterized by
oxidative stress, inflammatory reaction and excessive pulmonary cell apoptosis.
So we supposed that CO might have protection against LI. LI in rats was induced
by intravenous injection of LPS (5 mg/kg). To observe the effect of CO
inhalation, LI rats were exposed to 2.5 x 10(-4) (V/V) CO for 3 h. CO-induced
changes of lung oxidative stress parameters, inflammatory cytokines, cell
apoptosis, HO-1 expression and histology were examined. Results revealed that
expressions of the tumor necrosis factor-alpha (TNF-alpha) and interlukin-6 (IL
6), activities of maleic dialdehyde (MDA) and myeloperoxidase (MPO), and cell
apoptosis in LPS injection + CO inhalation group were (0.91+/-0.25) pg/mg
protein, (0.64+/-0.05) pg/mg protein, (1.02+/-0.23) nmol/mg protein, (7.18+/
1.62) U/mg protein and (1.60+/-0.34)%, respectively, significantly lower than the
corresponding values in LI group [(1.48+/-0.23) pg/mg protein, (1.16+/-0.26)
pg/mg protein, (1.27+/-0.33) nmol/mg protein, (8.16+/-1.49) U/mg protein and
(3.18+/-0.51) %, P<0.05]. Moreover, CO inhalation obviously increased the
expressions of HO-1 and interlukin-10 (IL-10) and activity of superoxide
dismutase (SOD) [(5.43+/-0.92), (0.26+/-0.07) pg/mg protein and (60.09+/-10.21)
U/mg protein in LPS injection + CO inhalation group vs (3.08+/-0.82), (0.15+/
0.03) pg/mg protein and (50.98+/-6.88) U/mg protein in LI group, P<0.05]. LI was
attenuated by CO inhalation. Our study demonstrates that inhalation of low
concentration of CO protects lung against LPS-induced injury via anti-oxidant,
anti-inflammation, anti-apoptosis and up-regulation of HO-1 expression.
PMID- 17041735
TI - [Formation of platelets from cord blood CD34+ cells-derived megakaryocytes
induced by S-nitrosoglutathione].
AB - To investigate the effect of S-nitrosoglutathione (GSNO), a nitric oxide donor,
on platelet production from megakaryocytes differentiated from cord blood CD34(+)
cells in vitro, the CD34 (+) cells from eight fresh umbilical cord blood samples
by a high-gradient magnetic cell sorting (MACS) system were cultured in serum
free medium for 14 d with thrombopoietin (TPO) 50 ng/ml, IL-3 10 ng/ml, stem cell
factor (SCF) 50 ng/ml and rHuGM-CSF 20 ng/ml. Then, CD61 (+) cells were purified
by MACS system from these CD34 (+) cells, and were cultured in serum-free medium
supplemented with TPO 50 ng/ml, IL-3 10 ng/ml and SCF 50 ng/ml in the presence
(treatment group) and absence (control group) of GSNO for 30 min or 2 h. Platelet
sized particles were counted by flow cytometry; megakaryocyte structure was
detected by scanning electron microscope. Aggregation of the thrombin-induced
platelet particle was observed under inversion microscope. cGMP was assessed by
commercial ELISA kit. The results showed that, compared with the control group,
the number of platelet-sized particles significantly increased (P<0.05) in the
treatment group, in which megakaryocytes presented significant pseudopod
formation and extensive membrane blebbing. The platelet particle aggregation
could be observed under microscope after thrombin induction. cGMP activity was
significantly increased after treatment with GSNO (P<0.05). These results propose
that GSNO can facilitate platelet production from megakaryocyte, and it may be
partly through cGMP pathway.
PMID- 17041736
TI - [Effect of 4 degrees C pretreatment on the membrane current and cell polarity in
human neutrophils].
AB - To investigate the role of ion channels in the coupling responses of neutrophils
to extracellular stimulus, it is necessary to study the membrane ion channel
activities using patch-clamp technique. However, little has been known about the
ion channel activities in neutrophils due to the difficulties in forming giga
seal with pipettes because of small diameter of neutrophils and the easily
developed polarization. Some studies indicated that favorable results could be
achieved through pretreatment at low temperature before electrophysiological
recordings. But it remains unclear whether the pretreatment affects the membrane
current and why the seal rate increases after low temperature pretreatment. The
purpose of this study was to investigate the effects of 4 degrees C pretreatment
on the membrane current and cell polarity in human neutrophils. In the
experiments, human neutrophils were isolated from fresh peripheral blood of
healthy volunteers and divided into two groups (room temperature group and 4
degrees C pretreatment group). Voltage-dependent K(+) (Kv) currents were recorded
in whole-cell voltage-clamp mode and large-conductance Ca(2+)-activated K(+)
(BK(Ca)) currents were recorded using inside-out patches. The results showed that
4 degrees C pretreatment significantly inhibited cell polarity (P<0.05), and it
took more time for neutrophils to form a polarity-cycle [(534+/-32) s, n=20]
compared with those at room temperature [(257+/-24) s, n=20]. Meanwhile, seal
rate significantly increased in 4 degrees C pretreatment group (64%) compared
with that in the room temperature group (27.5%). The seal rate and cell polarity
rate during 0 approximately 1 min after 4 degrees C pretreatment were
significantly different from those at room temperature, while no significant
difference was found during 9 approximately 10 min between the two groups. Our
results suggest that 4 degrees C pretreatment can inhibit cell polarity and
increase seal rate, but has no effects on membrane currents. It is also suggested
that 0 approximately 1 min after 4 degrees C pretreatment is a more suitable time
for electrophysiological recording in neutrophils.
PMID- 17041738
TI - Meningomyeloradiculitis as presenting feature of brucellosis.
PMID- 17041737
TI - Characteristics associated with involuntary versus voluntary legal status at
admission and discharge among psychiatric inpatients.
AB - BACKGROUND: The objective of this analysis was to determine the ways in which
patients' legal statuses at hospital admission and discharge are associated with
select sociodemographic and clinical variables. This study specifically
investigated differences between patients who were voluntary during both
admission and discharge, patients who were involuntary on admission but voluntary
on discharge (having converted to voluntary status during hospitalization), and
patients who were involuntary during both admission and discharge. METHOD: Data
were collected from the charts and treating clinicians of 227 consecutively
discharged patients from two psychiatric units in a large, urban, county hospital
in the southeastern United States. Based on results of bivariate tests,
sociodemographic and clinical factors were entered into a polytomous logistic
regression model to determine effect estimates (adjusted odds ratios). RESULTS:
In the bivariate analyses, 15 variables were significantly associated with the
trichotomous legal status. In the model, three factors were independently
significantly associated with legal status, while controlling for four potential
confounders: (1) whether or not the patient was experiencing psychotic symptoms
at discharge, (2) whether or not the patient had documented medical problems
requiring medication at discharge, and (3) the number of psychiatric medications.
CONCLUSIONS: A generalized lack of treatment engagement and adherence among
involuntary patients likely underlies significant differences between the groups
in terms of psychotic symptoms, diagnosed medical problems requiring medications,
and number of psychiatric medications at discharge. Studying legal status (and
the process of legal status conversion from involuntary to voluntary) and its
correlates is an important topic for further research.
PMID- 17041739
TI - Frontal diaschisis in a German case of fatal familial insomnia.
PMID- 17041740
TI - Differentiating Alzheimer's disease from subcortical vascular dementia with the
FAB test.
AB - BACKGROUND: The frontal assessment battery (FAB) test is a composite tool for
assessing executive functions related to the frontal lobe. Neuropsychological and
blood-flow studies indicate distinct patterns of deterioration of anterior and
posterior cortical function in Alzheimer's disease (AD) and subcortical vascular
dementia (VD) patients. We predict that the FAB score may be useful for
discriminating VD from AD. OBJECTIVE: To evaluate the clinical usefulness of the
FAB test for differential diagnosis of AD and VD. METHODS: We compared FAB scores
in 25 patients with AD, 27 patients with VD, and 80 age-matched normal control
subjects. The AD group was matched for age, education and MMSE score with the VD
group. The subtest scores in FAB were also compared among the three groups.
RESULTS: The FAB scores were significantly decreased in both the AD and VD groups
compared to the control group, and the reduction were greater in the VD group.
Among the FAB subtests, mental flexibility (phonological verbal fluency) was the
only subtest that significantly discriminated VD from the other two groups.
CONCLUSIONS: The FAB test can provide useful information for differentiating AD
and VD at the bedside.
PMID- 17041742
TI - Anomalous thermal denaturing of proteins adsorbed to nanoparticles.
AB - We have used localized surface plasmon resonance (LSPR) to monitor the structural
changes that accompany thermal denaturing of bovine serum albumin (BSA) adsorbed
onto gold nanospheres of size 5nm-60nm. The effect of the protein on the LSPR was
monitored by visible extinction spectroscopy. The position of the resonance is
affected by the conformation of the adsorbed protein layer, and as such can be
used as a very sensitive probe of thermal denaturing that is specific to the
adsorbed protein. The results are compared to detailed calculations and show that
full calculations can lead to significant increases in knowledge where gold
nanospheres are used as biosensors. Thermal denaturing on spheres with diameter >
20 nm show strong similarity to bulk calorimetric studies of BSA in solution. BSA
adsorbed on nanospheres with d [Symbol: see text] 15nm shows a qualitative
difference in behavior, suggesting a sensitivity of denaturing characteristics on
local surface curvature. This may have important implications for other protein
nanoparticle interactions.
PMID- 17041741
TI - Impaired baroreflex function in temporal lobe epilepsy.
AB - Changes of cardiovascular function are frequent in temporal lobe epilepsy (TLE).
The baroreflex - the most important reflex for cardiovascular stability - has not
been studied systematically in TLE. We evaluated cardiovascular variability and
baroreflex function in TLE. In 22 TLE patients and 20 controls, we continuously
monitored heart rate (HR) and blood pressure (BP). Time-domain parameters were
derived from recordings at rest and from standard cardiovascular reflex tests.
Spectral analysis determined sympathetic and parasympathetic modulation of HR and
BP in the low (LF-power) and high frequency range (HF-power). We calculated the
relative LF- and HF-powers of HR in relation to the sum of LF- and HF-powers.
LF/HF-ratio of HR was assessed as a parameter of sympatheticovagal balance. LF
transfer function gain between BP and HR determined baroreflex function.Time
domain parameters did not differ between TLE patients and controls. Spectral
analysis showed decreased absolute LF- and HF-powers but increased relative LF
power and LF/HF-ratio of HR in TLE. LF-transfer function gain between BP and HR
was reduced in TLE (p<0.05). The reduction of absolute LF- and HF-powers
indicates decreased total autonomic variability in TLE. However, increased
relative LF-power and LF/HF-ratio of HR in TLE show a relative increase of
sympathetic tone. Most importantly, we demonstrate an impaired baroreflex
function in TLE. These cardiovascular autonomic abnormalities may contribute to
cardiac arrhythmia in TLE.
PMID- 17041743
TI - Wormlike lipid/DNA micelles in a non-polar solvent.
AB - The phase behavior of DOPE/DOTAP-DNA complexes in phase-separated
oil(dodecane)/water mixtures was explored using Small Angle X-Ray Scattering
(SAXS) and Fluorescence Correlation Spectroscopy (FCS). Inverse micelles of DNA
with cationic-lipid coating were found in the oil phase. Varying the ratio
between cationic and neutral lipids a transition from wormlike to spherical
structures is observed for both long ( approximately 75000bp) and short (30
1246bp) DNA. In contrast to lipid/DNA complexes in the water phase, there is no
indication of condensed liquid-crystalline structures in the non-polar phase. In
fact, FCS measurements on short DNA oligomers complexed with cationic lipid in
alkane give clear evidence for monomeric inverse micelles of DNA. Dilution series
revealed a critical lower concentration of lipids and DNA for observing lipid/DNA
micelles.
PMID- 17041744
TI - Sudden deterioration in nonclassical infantile-onset Pompe disease responding to
alglucosidase alfa infusion therapy: a case report.
AB - A patient with atypical infantile Pompe disease suffered acute respiratory
insufficiency at the age of 8 years which resulted in complete immobilization and
dependence on assisted ventilation. Shortly after initiation of enzyme
replacement therapy, she regained her mobility and, after 20 months of treatment,
she now leads an almost normal life with limited restrictions.
PMID- 17041745
TI - The aetiology of neurological complications of organic acidaemias--a role for the
blood-brain barrier.
AB - The blood-brain barrier (BBB) metabolically isolates the central nervous system
(CNS) from the circulation and protects it against fluctuations of hydrophilic
nutrients in plasma and from intoxication. Recent studies have shown that
dicarboxylic acids (DCAs) are transported across the blood-brain barrier at very
low rates. In organic acidaemias, neurological complications are common. We
hypothesize that, as a result of the very limited efflux, in certain organic
acidaemias there is pathological accumulation of DCAs (e.g. glutarate, 3
hydroxyglutarate, D-2- and L-2-hydroxyglutarate, methylmalonate) in the brain
secondary to the metabolic block. At high concentrations some of these compounds
may become neurotoxic. Treatment should be aimed at preventing the accumulation
of these compounds using our understanding of the properties of the BBB.
PMID- 17041746
TI - Mutational spectrum of classical galactosaemia in Spain and Portugal.
AB - Classical galactosaemia is an autosomal recessive inherited metabolic disorder
due to deficient galactose-1-phosphate uridyltransferase (GALT). Over 180
different base changes and disease-causing mutations have been reported in the
GALT gene. Mutation p.Q188R was found to be the most common molecular defect
among caucasian classical galactosaemia patients. We have characterized the
spectrum of GALT mutations in a group of 51 Spanish families and 32 Portuguese
families with this disease. p.Q188R is also the most prevalent mutation in the
Spanish and Portuguese population, accounting for 50% and 57.8% of galactosaemic
alleles, respectively. An additional 15 mutations were also identified in Spanish
patients, four of which were novel: p.D28H, p.S181A, c.658dupG and
c.377+53_1059+87del. In the Portuguese population, 11 different mutations were
found, three of which were novel: p.R33H, p.P185S, and p.S192G. The differences
observed between the genotypes identified in Portuguese and Spanish galactosaemic
populations are notable. Only mutations p.Q188R, p.R148Q and c.820+13g>a were
identified in both populations. In spite of the geographical proximity of Spain
and Portugal, it seems that they have received genetic influences from different
populations. The repeated migrations that occurred in the Iberian Peninsula
throughout centuries may explain such variability.
PMID- 17041747
TI - Preclinical assessment of anthracycline cardiotoxicity in laboratory animals:
predictiveness and pitfalls.
AB - Doxorubicin is one of the most prescribed anticancer drugs, due to its important
activity in hematological malignancies as in solid tumors. However, its important
cardiac toxicity still limits its long-term use and prevents from reaching
optimal benefits. Numerous ways have been proposed to avoid cardiac toxicity,
such as protracted infusions or special formulations, development of less
cardiotoxic analogues and of cardioprotectors. There is a need for preclinical
models able to screen rapidly these various approaches and to provide rational
bases for clinical trials. The first model is the long-term rabbit model.
Weanling rabbits given weekly injections of doxorubicin for 4 months developed a
cardiomyopathy which was obvious from a clinical (cardiac failure) and from a
pathological point of view. This model has been widely used afterwards for the
discovery of cardioprotective molecules. Models in other animals such as rats or
mice were similarly implemented, also with long-term exposures to the drug,
resulting in cardiac failure and severe pathological alterations which could be
graded for comparison. Starting from the evidence that the damage caused by
anthracyclines on cardiomyocytes was immediate after each injection and that the
functional efficiency of the myocardium should be affected by the anthracyclines
long before the morphological alterations become detectable, we developed a short
term model studying the cardiac performances of isolated perfused hearts of rats
that had been treated within 12 days by repetitive administrations of the
molecule(s) to be tested. This model appeared easy to implement and provided the
data expected from clinical experience: epirubicin appeared less cardiotoxic than
doxorubicin; liposomal formulations appeared less cardiotoxic than free drug
formulations; dexrazoxane strongly protected against doxorubicin cardiotoxicity.
We were then to show that paclitaxel could potentiate doxorubicin cardiotoxicity,
but that docetaxel did not so; or that a high dose of dexrazoxane brought
significantly higher protection than a conventional dose. Based upon these
various contributions, we can encourage the use of the short-term model of
isolated perfused rat heart to screen the preclinical cardiotoxicity of
anthracycline molecules, formulations and combinations.
PMID- 17041748
TI - An evidence-based, multidisciplinary approach to the clinical considerations,
management, and surveillance of adrenal lesions in familial adenomatous
polyposis: report of three cases.
AB - Adrenal masses are commonly discovered incidentally in patients with familial
adenomatous polyposis, and adrenal malignancies have been rarely reported.
Individuals with familial adenomatous polyposis frequently undergo abdominal CT
scan examinations for surveillance or symptoms. Adrenal lesions often are
detected unexpectedly and are thus becoming a common clinical problem in this
population. Adrenal lesions encompass a heterogeneous spectrum of pathologic
entities, including primary adrenocortical and medullary tumors, benign or
malignant lesions, hormonally active or inactive lesions, metastases, and
infections. When an adrenal mass is detected, the clinician needs to address two
crucial questions: 1) is the mass malignant? and 2) is it hormonally active? This
article presents three new cases of incidental adrenal lesions in familial
adenomatous polyposis, reviews the medical literature for this setting, and
provides an overview of the diagnostic clinical approach and management of the
adrenal findings in familial adenomatous polyposis patients.
PMID- 17041749
TI - Indication and benefit of pelvic sidewall dissection for rectal cancer.
AB - PURPOSE: This study was designed to clarify indication and benefit of pelvic
sidewall dissection for rectal cancer. METHODS: The retrospective, multicenter
study collected the data of rectal cancer patients who underwent surgery between
1991 and 1998 and were prospectively followed. RESULTS: Of 1,977 patients with
rectal cancers, 930 underwent pelvic sidewall dissection without adjuvant
radiotherapy. Positive lateral lymph nodes were found in 129. Multivariate
analysis disclosed a significantly increased incidence of positive lateral lymph
nodes in female gender, lower rectal cancers, non-well-differentiated
adenocarcinoma, tumor size of > or =4 cm and T3-T4. The five-year survival rate
for 1,977 patients was 79.7 percent. The survival of patients with positive
lateral lymph nodes was significantly worse than that of Stage III patients with
negative lateral lymph nodes (45.8 vs. 71.2 percent, P<0.0001). Multivariate
analysis showed significantly worse prognosis in male gender, pelvic sidewall
dissection, lower rectal cancers, T3-T4, perirectal lymph node metastasis, and
positive lateral lymph nodes. During the median follow-up time of 57 months,
recurrence developed in 19.7 percent: 17 percent in negative and 58.1 percent in
positive lateral lymph nodes (P<0.0001). Local recurrence was found in 8 percent:
6.8 percent in negative and 25.6 percent in positive lateral lymph nodes
(P<0.0001). Multivariate analysis disclosed that lower rectal cancers, non-well
differentiated adenocarcinoma, T3-T4, perirectal lymph node metastasis, and
positive lateral lymph nodes were significantly associated with an increased
local recurrence. CONCLUSIONS: Positive lateral lymph node was the strongest
predictor in both survival and local recurrence. Pelvic sidewall dissection may
be indicated for patients with T3-T4 lower rectal cancers because of the greater
probability of positive lateral lymph nodes.
PMID- 17041750
TI - Measurement of health-related quality of life in the early follow-up of colon and
rectal cancer.
AB - PURPOSE: Little is known about factors that affect health-related quality of life
during the early follow-up of colorectal cancer. This study was designed to
identify the factors that contribute to poor health-related quality of life after
six weeks of follow-up and to compare the relative performance of instruments
best suited to measure it. METHODS: A single-center, prospective study was
designed to examine health-related quality of life after potentially curative
surgery for colorectal cancer. Two condition-specific and two generic instruments
(QLQ-C30, FACT-C, SF12 and EQ-5D) measured quality of life six weeks after
discharge. Univariate and multivariate analyses were used to assess the impact of
16 treatment factors, demographic variables, and symptoms on seven global health
related quality of life scores. RESULTS: Questionnaires were obtained from 201
consecutive patients. Five factors were associated with poor health-related
quality of life scores at six-week follow-up in the multivariate analysis:
reduced preoperative performance status, stomas, diarrhea, constipation, and
younger than aged 65 years. No instrument out performed the others. However,
condition-specific instruments and those in which patients subjectively rated
their overall health-related quality of life were better suited to detect health
related quality of life differences relating to the effects of colorectal cancer
treatment. CONCLUSIONS: Younger patients, those with stomas, and those suffering
from diarrhea or constipation are more likely to report poor health-related
quality of life at six-week follow-up. The routine measurement of health-related
quality of life using an instrument that includes a patient-rated scale together
with condition-specific items could be used to detect patients at risk of poorer
short-term health-related quality of life outcomes.
PMID- 17041751
TI - Practice parameters for the prevention of venous thrombosis.
PMID- 17041752
TI - Effect of aging on anorectal and pelvic floor functions in females.
AB - PURPOSE: In females, fecal incontinence often is attributed to birth trauma;
however, symptoms sometimes begin decades after delivery, suggesting that
anorectal sensorimotor functions decline with aging. METHODS: In 61 asymptomatic
females (age, 44 +/- 2 years, mean +/- standard error of the mean) without risk
factors for anorectal trauma, anal pressures, rectal compliance, and sensation
were assessed by manometry, staircase balloon distention, and a visual analog
scale during phasic distentions respectively. Anal sphincter appearance and
pelvic floor motion also were assessed by static and dynamic magnetic resonance
imaging respectively in 38 of 61 females. RESULTS: Aging was associated with
lower anal resting (r = -0.44, P < 0.001) and squeeze pressures (r = -0.32, P =
0.01), reduced rectal compliance (i.e., r for pressure at half-maximum volume vs.
age = 0.4, P = 0.001), and lower (P 7 cm,
53%; 0.9). Gains were comparable
in size with those previously reported for participants who received equal
intensities of directly supervised AutoCITE training or standard one-on-one CI
therapy without the device.
PMID- 17041825
TI - Relationships between upper-limb functional limitation and self-reported
disability 3 months after stroke.
AB - This study explored relationships between upper-limb (UL) functional limitations
and self-reported disability in stroke patients with relatively pure motor
hemiparesis who were enrolled in an acute rehabilitation treatment trial. All
participants were enrolled in the VECTORS (Very Early Constraint Treatment for
Recovery from Stroke) study. VECTORS is a single-center pilot clinical trial of
early application of constraint-induced movement therapy (CIMT). All 39 subjects
who completed 90 days of VECTORS were included in this analysis. Trained study
personnel who were blinded to the treatment type performed all evaluations. Data
in this article examine relationships between assessments performed 90 days after
stroke. Functional limitation measures included the Action Research Arm (ARA)
test and Wolf Motor Function Test (WMFT), and self-reported disability measures
included the Functional Independence Measure (FIM) and Motor Activity Log (MAL)
(by telephone). Mean plus or minus standard deviation time from stroke onset to
randomization was 9.4 plus or minus 4.3 days, and median time to follow-up was 99
days (range 68-178). Subjects with perfect or near-perfect scores on the ARA test
or WMFT reported residual disability on the FIM and MAL. Quality of movement on
the WMFT (functional ability score) was not strongly associated with self
reported frequency, and speed of movement on the WMFT (timed score) was not
associated with self-reported frequency (MAL amount of use). In this early UL
intervention trial, we found that perceived disability measures captured
information that was not assessed by functional limitation and impairment scales.
Our results indicate that excellent motor recovery as measured by functional
limitation and impairment scales did not equal restoration of everyday productive
UL use and speed of task completion did not translate to actual use. Our results
confirm the need for a measurement strategy that is sensitive to change, assesses
a broad performance range, and detects meaningful clinical improvements in early
rehabilitation intervention trials.
PMID- 17041826
TI - Influence of intensive phonomotor rehabilitation on apraxia of speech.
AB - In this phase I rehabilitation study, we investigated the effects of an intensive
phonomotor rehabilitation program on verbal production in a 73-year-old male, 11
years postonset a left-hemisphere stroke, who exhibited apraxia of speech and
aphasia. In the context of a single-subject design, we studied whether treatment
would improve phoneme production and generalize to repetition of multisyllabic
words, words of increasing length, discourse, and measures of self-report. We
predicted that a predominant motor impairment would respond to intensive
phonomotor rehabilitation. While able to learn to produce individual sounds, the
subject did not exhibit generalization to other aspects of motor production.
Discourse production was judged perceptually slower in rate and less effortful,
but also less natural. Finally, self-report indicated less apprehension toward
speaking with unfamiliar people, increased telephone use, and increased ease of
communication.
PMID- 17041827
TI - Using the magnetic resonance three-dimensional volume rendering for tissues
technique in the planning of craniotomy flaps with linear scalp incision.
AB - Preoperative three-dimensional images with surface venous anatomy may be used in
the planning of a linear scalp incision and the opening site of the dura mater
for protection of surface veins during surgical dissection, and to find the
splitting site of the brain according to the lesion. In 45 patients who had a
brain tumor, linear scalp incision planning was done by regarding the three
dimensional images derived from post-contrast time-of-flight (TOF) sequence raw
data. The findings of correspondence and the quality of routine contrast-enhanced
magnetic resonance imaging (MRI) and three-dimensional volume rendering for
tissues (VRT) images were analyzed separately with the surgical findings
according to a visual grading system. Our experience revealed that the surgical
findings correlated well with the three-dimensional VRT images. According to a
visual surgical grading system, a grade III correlation was found in 20 (45%),
grade II in 15 (33%), grade I in 7 (15%), and grade 0 in 3 (7%) patients in our
study population. At the end of our research we conclude that this method is
useful in terms of the preoperative determination of brain surface anatomy and
may be used in the determination of the site of a linear scalp incision according
to the localization of an intracranial lesion.
PMID- 17041828
TI - Endoscopic management of thalamic gliomas.
AB - The management of thalamic gliomas is extremely variable, ranging from radical
excision in some cases to more conservative therapy such as a biopsy and
radiation. There is a high incidence of associated hydrocephalus. The principles
of management are, therefore, histological diagnosis, CSF diversion and adjuvant
therapy. Endoscopy appears to offer a new approach to achieve histology and CSF
diversion. The various goals achieved with the use of endoscopy in the management
of 4 patients with thalamic gliomas are described. With the endoscope we achieved
histological diagnoses and CSF diversion was facilitated in all these cases.
There were no complications. The advantages of endoscopy in the management of
thalamic masses are discussed. Endoscopic intervention appears to offer a modular
approach to these lesions.
PMID- 17041829
TI - Application of intraoperative 3D ultrasound during navigated tumor resection.
AB - Intraoperative 3D ultrasound (3D-iUS) may enhance the quality of neuronavigation
by adding information about brain shift and tumor remnants. The aim of our study
was to prove the concept of 3D ultrasound on the basis of technical and human
effects. A 3D-ultrasound navigation system consisting of a standard personal
computer containing a video grabber card in combination with an optical tracking
system (NDI Polaris) and a standard ultrasound device (Siemens Omnia) with a 7.5
MHz probe was used. 3D-iUS datasets were acquired after craniotomy, at different
subsequent times of the procedure and overlaid with preoperative MRI. All
patients underwent early postoperative 3D MRI including contrast agent within 24
hours after surgery. Acquisition of 3D iUS and the fusion with preoperative MRI
was successful in 22/23 patients. The expenditure of time was at least 5 minutes
for one intraoperative 3D US dataset. The technique was used three to seven times
during surgery. The quality of the ultrasound images was superior in cases of
metastasis, meningeoma and angioma over those in malignant glioma. Brain shifting
ranged from 2-25 mm depending on localization and kind of tumor. A resection
control was possible in 78%. All six neurosurgeons demonstrated a learning curve.
The introduction of 3D ultrasound has increased the value of neuronavigation
substantially, making it possible to update several times during surgery and
minimize the problem of brain shift. Configuration of both the 3D iUS based on a
standard ultrasound system and the MR navigation system is time- and especially
cost-effective. Faster navigational datasets and more intuitive image-guided
surgery enable novel and user-friendly display techniques.
PMID- 17041830
TI - The role of cyberknife radiosurgery/radiotherapy for brain metastases of multiple
or large-size tumors.
AB - OBJECTIVE: Focused, highly targeted radiosurgery and fractionated radiotherapy
using the Cyberknife are useful treatments for multiple or large metastases. Here
we present our results of Cyberknife radiosurgery for 71 patients with 148
metastatic brain lesions. METHODS: There were 32 women and 39 men with a median
age of 63 (range: 30-88) years. Radiographic follow-up was available for 60
patients with 104 lesions. The mean and median initial volumes of the tumor per
lesion were 6.6 and 2.9 cm(3) (range: 0.1-53.2 cm(3)), respectively, at the time
of the initial Cyberknife treatment. Forty patients (56%) had a single lesion,
and 31 (44%) had multiple lesions (range: 2-7) at initial treatment. The number
of fractions ranged from 1 to 3, and forty (27%) of 148 lesions were treated by a
fractionated course of Cyberknife therapy. The mean marginal dose was 20.2 Gy
(range 7.8-30.1 Gy, median: 20.7 Gy). RESULTS: At 44 weeks of median follow-up,
there were no permanent symptoms resulting from radiation necrosis. Overall 6
month and 1-year survival rates were 74% and 47%, respectively, and the median
survival time was 56 weeks. The Karnofsky performance score and extracranial
metastasis were significant prognostic factors at 6 months and 1 year,
respectively, in both univariate and multivariate analyses. Age or multiple
metastases did not influence prognosis at 6 months and 1 year. Local control was
achieved in 83% (86 lesions). After additional radiosurgical or surgical salvage,
no patient died as a result of intracranial disease. Twenty-five patients
developed 92 new metastases (range 1-13) outside of the treated lesions with 22.4
weeks of median follow-up. Among them, 21 patients (84 lesions) were treated by
salvage Cyberknife. CONCLUSION: Despite the inclusion of an unfavorable group of
patients with large tumors, our results for survival and tumor control rates are
comparable to those of published series. The Cyberknife provides the advantage of
allowing for fractionated treatment to multiple or large-size tumors.
PMID- 17041831
TI - Application of neuronavigation system to brain tumor surgery with clinical
experience of 420 cases.
AB - A new era of neurosurgery has recently been unveiled with the advent of image
guided surgery. The use of neuronavigation is beginning to have a significant
impact on a variety of intracranial procedures. Herein, we report our clinical
experience using a neuronavigation system with different surgical applications
and techniques for a variety of brain tumors. We used the BrainLab VectorVision
neuronavigation system, which is a frameless and image-guided system. We operated
on 420 cases having various types of brain tumor with the help of this system.
The mean target localizing accuracy and mean volume were 1.15 mm and 30.8 mL (0.2
216.4 mL), respectively. We utilized this system to effectively make bone flaps,
to detect critically located, deep-seated, subcortical, skull-base and skull bone
tumors, and to operate on intraparenchymal lesions with grossly unclear margins,
such as gliomas. We also performed tumor biopsy using the combination of a
conventional stereotactic biopsy instrument and an endoscope. The application of
the neuronavigation system not only revealed benefits for operative planning,
appreciation of anatomy, lesion location and the safety of surgery, but also
greatly enhanced surgical confidence.
PMID- 17041832
TI - Endoscopic carpal tunnel release in the elderly.
AB - The present study is aimed to clarify the postoperative outcome of endoscopic
carpal tunnel release in elderly patients with carpal tunnel syndrome. Endoscopic
carpal tunnel release was performed on 37 hands of 27 patients (2 men, 25 women)
who were aged 70 years or older and clinically and electrophysiologically
diagnosed with carpal tunnel syndrome. Mean age at the time of surgery was 74.5
years (range: 70-85 years). Mean postoperative follow-up was 35.5 months (range:
12-114 months). Pain was present preoperatively in 20 hands, but quickly resolved
postoperatively in all cases. Numbness completely disappeared in 13 of 37 hands
(35.1%), but some degree of numbness remained in the remaining cases.
Preoperative severity of thenar muscle atrophy was none in 4 hands, mild in 7
hands, moderate in 12 hands and severe in 14 hands. Postoperative severity of
thenar muscle atrophy at final follow-up was none in 13 hands, mild in 16 hands,
moderate in 2 hands and severe in 6 hands, confirming that thenar muscle atrophy
improves even in elderly patients. However, moderate or severe thenar muscle
atrophy remained in 8 hands (21.6%). Endoscopic carpal tunnel release should be
considered in the elderly, even though clinical symptoms may not improve
substantially in advanced cases.
PMID- 17041833
TI - Morphological study of the spinal canal content for subarachnoid endoscopy.
AB - STUDY DESIGN AND OBJECTIVE: This study was designed to examine the morphology of
the spinal dural sac and contents, using magnetic resonance imaging in order to
define the inner geometrical dimensions that confine the manoeuvre of an
endoscope inserted in the lumbar region and along the thoracic and cervical
spine. BACKGROUND: The morphology of the spine has been studied since the
development of myelography. However, most studies have measured the diameters of
the spinal cord only, not the size of the subarachnoid space. In addition, the
few studies available on the subarachnoid space have focused on the cervical
spine, leaving a near-complete dearth of data on the subarachnoid space
dimensions along the thoracic spine. METHODS: Based on MRI images of the spine
from 42 patients, the dimensions of the spinal cord, dural sac, and subarachnoid
space were measured at mid-vertebral and inter-vertebral disc levels. RESULTS: It
was found that at each selected transverse level, the subarachnoid space tends to
be symmetrical on the right and left sides of the cord, and measures 2.5 mm on
average. However, the posterior and anterior segments, measured on the mid
sagittal plane, are generally asymmetrical and vary widely in size, ranging from
1 to 5 mm. These measurements match those found in previous studies, where these
are available. The coefficient of variance for the dimensions of the subarachnoid
space is as high as 42.4%, while that for the dimensions of the spinal cord is 10
15%. CONCLUSIONS: The findings presented here expand our knowledge of the spinal
canal's morphology, and show that an endoscope designed to travel within the
subarachnoid space must be smaller than 2.5 mm in diameter.
PMID- 17041834
TI - Open-window laparotomy during a transperitoneal approach to the lower lumbar
vertebrae: new method for reducing complications.
AB - There are numerous approaches for exploring the lower lumbar vertebrae, and the
anterior transperitoneal route is one of the most popular. Like all surgical
techniques, this approach has advantages and disadvantages. It provides direct
access to the target tissue through a small incision, exposes the anterior
portion of the vertebrae well, and permits good visualization of the major
vessels, thus reducing risk of vascular injury and life-threatening hemorrhage.
However, compared to the extraperitoneal route, the transperitoneal approach
carries higher risks for peritoneal complications. This article describes a new
practical method for creating an extraperitoneal passageway or "window" during
transperitoneal approaches to the lower lumbar vertebrae. Isolation of the
peritoneal cavity and its contents with this technique can reduce peri- and
postoperative abdominal complications.
PMID- 17041835
TI - Trigeminal neuroma with extracranial extension: the 31st case.
AB - Neuromas arising from the distal branches of the trigeminal nerve with
extracranial extension are unusual. Here, we present the clinical features,
diagnosis and treatment of 28-year-old woman with trigeminal neuroma with
extension to the infratemporal fossa.
PMID- 17041836
TI - "Triple cross" of the hypoglossal nerve and its microsurgical impact to
entrapment disorders.
AB - OBJECTIVE: Cadaveric dissections were performed to review the intracranial and
extracranial course of the hypoglossal nerve. The neurological significance of a
newly defined "triple cross" of the hypoglossal nerve is discussed. MATERIALS AND
METHODS: 10 cadaveric heads (left and right; 20 sides) were dissected using
microsurgical techniques. RESULTS: In the cisternal segment of hypoglossal nerve,
the diameter of the rostral trunk amounted to 155-680 microm (mean 435 microm),
and the caudal trunk to 210-820 microm (mean 482 microm). The roots formed three
trunks in 20% of the hypoglossal nerves and two trunks in the rest. As a first
cross, the anterior medullary segment of the vertebral artery crossed the
hypoglossal nerve roots in 14 of 20 sides (70%). As a rare variation, the
vertebral artery extended medial to the nerve (25%) or between its roots (5%).
The second cross was found between the descendens hypoglossus and the occipital
artery (75%), sternocleidomastoid artery and vein complex (15%) and external
carotid artery (10%). The third cross was shown in the submandibular triangle
between the lingual hypoglossus and its drainage vein; vena committans nervus
hypoglossus. CONCLUSION: Throughout its way, the hypoglossal nerve passes over
vascular structures in three crossing points which may serve as a probable cause
of hypoglossal nerve entrapment disorders.
PMID- 17041837
TI - Outcome prediction of third ventriculostomy: a proposed hydrocephalus grading
system.
AB - An important factor in making a recommendation for different treatment modalities
in hydrocephalus patients (VP shunt versus endoscopic third ventriculostomy) is
the definition of the underlying pathology which determines the prognosis/outcome
of the surgical procedure. Third ventriculostomies (3rd VS) are successful mainly
in obstructive hydrocephalus but also in some subtypes of communicating
hydrocephalus. A simple, easily applicable grading system that is designed to
predict the outcome of 3rd VS is proposed. The hydrocephalus is graded on the
basis of the extent of downward bulging of the floor of the third ventricle,
which reflects the pressure gradient between the 3rd ventricle and the basal
cisterns, presence of directly visualised CSF pathway obstruction in MRI, and the
progression of the clinical symptoms resulting in five different grades. In this
proposed grading system, grade 1 hydrocephalus subtype shows no downward bulged
floor of the 3rd ventricle, no obstruction of the CSF pathway, and no progressive
symptoms of hydrocephalus. There is no indication for 3rd VS. Grades 2 to 4 show
different combinations of the described parameters. Grade 5 subtype shows a
markedly downward bulged floor of the 3rd ventricle and direct detection of the
CSF pathway obstruction (i.e., aqueductal stenosis) with progressive clinical
deterioration. Retrospective application of this grading scheme to a series of 72
3rd VS has demonstrated a high correlation with the outcome: The success rate in
grade 3 reached 40%, in grade 4: 58%, and in grade 5: 95%. This standardised
grading system predicts the outcome of 3rd VS and helps in decision making for
3rd VS versus VP shunting.
PMID- 17041838
TI - Endoscopic removal of ethmoido-sphenoidal foreign body with intracranial
extension.
AB - We describe the case of a foreign body lodged into ethmoidal labyrinth and
sphenoidal sinus with fracture of the clivus and consequent rhinoliquorrhea
removed by an endoscopic technique. We performed a skull base plasty to close the
rhino-liquoral fistula with resolution of the rhinoliquorrhea. There were no
postoperative complications and there was a good therapeutic result at long-term
follow-up.
PMID- 17041839
TI - Neuroendoscopic management of a solitary pineal region tumor. Case report of an
adenocarcinoma metastasis.
AB - The present case describes a two-step endoscopic management of hydrocephalus and
diagnosis of a single pineal region metastasis arising from a gastric
adenocarcinoma. A 62-year-old man presenting with signs of subacute obstructive
hydrocephalus from a pineal region mass had at first been treated with an
endoscopic third ventriculostomy. As cerebrospinal fluid tumor markers (alpha
fetoprotein, beta-human chorionic gonadotropin) were negative, an endoscopic
biopsy of the pineal region tumor was performed through a more anterior frontal
burr hole. Pathology showed an adenocarcinoma and primary tumor work-up revealed
an unsuspected gastric tumor, the pathology of which matched with the
intracranial metastasis. The present report emphasizes the role of neuroendoscopy
in pineal region tumors and reports a rare case of a solitary gastric
adenocarcinoma metastasis in this location.
PMID- 17041840
TI - Fatal intratumoral hemorrhage immediately after gamma knife radiosurgery for
brain metastases: case report.
AB - Radiosurgical treatment of brain tumors is sometimes considered to be free from
significant acute complications or adverse effects. A rare case of fatal
intratumoral hemorrhage immediately after gamma knife radiosurgery (GKR) for
brain metastasis is reported. A 46-year-old woman with lung cancer complicated by
systemic dissemination experienced an acute episode of headache, speech
disturbances, and right-side hemiparesis. She had no history of arterial
hypertension or coagulation disorders. CT and MRI disclosed multiple brain
metastases. The largest tumor, which was located in the left frontal lobe and
caused a significant mass effect, was removed microsurgically without any
complications. GKR for nine residual metastases was done on the fourth
postoperative day. The marginal dose, which corresponded to the 50% prescription
isodose line, constituted 20 Gy. No complications were noticed during frame
fixation, treatment itself, or frame removal. Fifteen minutes after the end of
the GKR session the patient acutely fell into a deep coma. Urgent CT disclosed a
massive hemorrhage in the left cerebellar hemisphere in the vicinity of the
radiosurgically treated lesion. The patient died 4 days later and autopsy
confirmed the presence of intratumoral hemorrhage. In conclusion, GKR for
metastatic brain tumors should not be considered as a risk-free procedure and,
while extremely rare, even fatal complications can occur after treatment.
PMID- 17041841
TI - Endotherapy of Zenker's diverticulum using the needle-knife technique: long-term
follow-up.
AB - BACKGROUND AND STUDY AIMS: Endotherapy of Zenker's diverticulum by mucomyotomy of
the bridge between the diverticulum and the esophageal lumen has been introduced
as a promising alternative to surgical techniques. However the data on long-term
clinical outcome are limited. After poor results in four patients treated by
argon plasma coagulation, we studied the efficacy and the long-term outcome of
dissection using a needle-knife in a consecutive series of patients. PATIENTS AND
METHODS: Between December 2001 and November 2004, 31 consecutively treated
symptomatic patients (18 men; median age 69 years; range 52-92) with Zenker's
diverticulum were enrolled into this retrospective study. In all cases
mucomyotomy was performed with a needle-knife with the patient under conscious
sedation. The procedure was repeated in the case of incomplete relief from
dysphagia or of recurrent symptoms during follow-up. All patients completed
questionnaires on the frequency and severity of dysphagia, using a numeric
analogue scale, ranging from 0 (never/none/excellent) to 10 (each time of
swallowing/very severe/very bad). RESULTS: Endoscopic mucomyotomy was achieved in
all 31 patients, with initial symptomatic improvement. Repeat treatment was
required in 10 patients after a mean of 5.3 months, due to recurrence of
symptoms. During a mean follow-up period of 26 months (range 14-49), 26 patients
(84%) had long-term success of variable degree (65% with no or minimal remaining
symptoms); four patients (13%) had insufficient relief and wanted a repeat
treatment; and one patient (3%) underwent surgery. The success rate in the entire
group was 84% (26/31) including those with repeat treatment, and 61% (19/31) if
only success following a single treatment session was counted. Minor
complications such as subcutaneous or mediastinal emphysema were observed in 23%
and were conservatively managed. There were no major complications. CONCLUSIONS:
A single needle-knife mucomyotomy procedure can achieve long-term symptomatic
improvement in about two out of three cases of Zenker's diverticulum. The success
rate can be increased to above 80% by repeated sessions. Minor complications
occur frequently but they can be conservatively managed. Major complications were
not observed. Further long-term studies are warranted to elucidate the role of
endoscopy as a definitive single treatment, with determination of prognostic
parameters for a successful long-term outcome.
PMID- 17041842
TI - Food safety revisited.
PMID- 17041843
TI - Are second-line drugs necessary to control multidrug-resistant tuberculosis?
PMID- 17041844
TI - Human bocavirus: developing evidence for pathogenicity.
PMID- 17041845
TI - Use of streptogramin growth promoters in poultry and isolation of streptogramin
resistant Enterococcus faecium from humans.
AB - BACKGROUND: Virginiamycin use in poultry selects for Enterococcus faecium with
cross-resistance to quinupristin-dalfopristin, a drug for vancomycin-resistant E.
faecium in humans. We conducted an epidemiologic study of poultry exposures as
risk factors for human carriage of quinupristin-dalfopristin-resistant E.
faecium. METHODS: Rectal or fecal samples for E. faecium testing were obtained
from 567 newly admitted hospital patients and 100 healthy vegetarians.
Participants were interviewed regarding poultry exposure. Retail poultry washes
(160 conventional and 26 antibiotic free) were also tested for the presence of E.
faecium. Constitutive and inducible quinupristin-dalfopristin resistance were
assessed in E. faecium isolates, and resistance genes were identified by
polymerase chain reaction. RESULTS: E. faecium was isolated from 105 patients, 65
vegetarians, and 77 conventional and 23 antibiotic-free poultry washes.
Constitutive quinupristin-dalfopristin resistance was absent in human E. faecium,
but 56% of conventional poultry isolates were quinupristin-dalfopristin
resistant. Inducible quinupristin-dalfopristin resistance was more common in
samples from patients than in those from vegetarians and in washes of
conventional than antibiotic-free poultry. Higher poultry consumption was
associated with inducible quinupristin-dalfopristin resistance. vatE was present
in 38% of E. faecium isolates from patients and none from vegetarians. Touching
raw poultry was associated with the presence of vatE. CONCLUSIONS: Poultry
exposure is associated with a quinupristin-dalfopristin resistance gene and
inducible quinupristin-dalfopristin resistance in human fecal E. faecium. The
continued use of virginiamycin may increase the potential for streptogramin
resistant E. faecium infection in humans.
PMID- 17041846
TI - An outbreak of gastrointestinal illness and erythema nodosum from grated carrots
contaminated with Yersinia pseudotuberculosis.
AB - BACKGROUND: Outbreaks of Yersinia pseudotuberculosis infection have been
epidemiologically linked to fresh produce, but the bacterium has not been
recovered from the food items implicated. In May 2003, a cluster of
gastrointestinal illness and erythema nodosum was detected among schoolchildren
who had eaten lunches prepared by the same institutional kitchen. METHODS: We
conducted a case-control study and trace-back, environmental, and laboratory
investigations. Case patients had culture-confirmed Y. pseudotuberculosis O:1
infection, erythema nodosum, or reactive arthritis. Bacterial isolates from
clinical and environmental samples were compared using pulsed-field gel
electrophoresis (PFGE). RESULTS: Of 7392 persons at risk, 111 (1.5%) met the case
definition; 76 case patients and 172 healthy control subjects were enrolled in
the case-control study. Only raw grated carrots were significantly associated
with illness in a logistic-regression model (multivariable odds ratio, 5.7 [95%
confidence interval, 1.7-19.5]); a dose response was found for increasing amount
of consumption. Y. pseudotuberculosis O:1 isolates from 39 stool specimens and
from 5 (42%) of 12 soil samples that contained carrot residue and were obtained
from peeling and washing equipment at the production farm were indistinguishable
by PFGE. CONCLUSIONS: Carrots contaminated early in the production process caused
a large point-source outbreak. Our findings enable the development of evidence
based strategies to prevent outbreaks of this emerging foodborne pathogen.
PMID- 17041847
TI - Impact of vitamin A on selected gastrointestinal pathogen infections and
associated diarrheal episodes among children in Mexico City, Mexico.
AB - BACKGROUND: The overall effect of vitamin A supplementation on diarrheal disease
in community trials may result from its effect on specific diarrheal pathogens.
METHODS: We conducted a placebo-controlled, double-blind trial of the
prophylactic effect of vitamin A on gastrointestinal pathogen infections and
clinical symptoms among 188 children in Mexico City, Mexico, from January 1998 to
May 1999. Children 6-15 months of age were randomly assigned to receive either a
vitamin A supplement (for children <12 months of age, 20,000 international units
[IU] of retinol; for children > or =12 months of age, 45,000 IU of retinol) every
2 months or a placebo and were followed for up to 15 months. Stool samples,
collected semimonthly, were screened for enteropathogenic Escherichia coli
(EPEC), enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC),
enteroinvasive E. coli (EIEC), and Giardia lamblia. RESULTS: Vitamin A
supplementation reduced the prevalence of EPEC infections (rate ratio [RR], 0.52
[95% confidence interval {CI}, 0.23-0.86]) and led to shorter durations of both
EPEC and ETEC infections. Supplementation also reduced the prevalence of EPEC
associated diarrhea (RR, 0.41 [95% CI, 0.16-1.00]), EPEC-associated fever (RR,
0.15 [95% CI, 0.02-0.98]), and G. lamblia-associated fever (RR, 0.27 [95% CI,
0.13-0.80]). Finally, children who received vitamin A supplementation had shorter
durations of EPEC-associated diarrhea than did children who did not receive
supplementation but had longer durations of G. lamblia-associated diarrhea.
CONCLUSIONS: These results suggest that the effect of vitamin A supplementation
on clinical outcomes may be pathogen dependent.
PMID- 17041848
TI - Antituberculosis drug resistance in the south of Vietnam: prevalence and trends.
AB - BACKGROUND: There is limited evidence that the DOTS (directly observed therapy,
short course) strategy for tuberculosis (TB) control can contain the emergence
and spread of drug resistance in the absence of second-line treatment. We
compared drug-resistance levels between 1996 and 2001 in the south of Vietnam, an
area with a well-functioning DOTS program. METHODS: Sputum specimens were
collected from consecutively diagnosed patients with smear-positive TB at 40
randomly selected public TB clinics. Mycobacterium tuberculosis isolates were
tested for susceptibility to first-line drugs. RESULTS: Among 888 new patients in
2001, resistance to any drug was observed in 238 (26.3%), resistance to isoniazid
was observed in 154 (16.6%), resistance to rifampin was observed in 22 (2.0%),
resistance to ethambutol was observed in 12 (1.1%), resistance to streptomycin
was observed in 173 (19.4%), and resistance to both isoniazid and rifampicin
(multidrug resistance [MDR]) was observed in 20 (1.8% [95% confidence interval,
1.0%-3.3%]). Among 136 previously treated patients in 2001, any resistance was
observed in 89 (62.9%), and MDR was observed in 35 (23.2%). The prevalence of any
drug resistance and of streptomycin resistance among new patients had decreased
significantly (P<.01) since 1996; there was no increase in the prevalence of MDR.
CONCLUSION: The prevalence of drug resistance decreased despite high initial
levels of resistance to isoniazid and streptomycin and despite the absence of
second-line treatment. Therefore, a DOTS program can contain drug-resistant TB in
this setting.
PMID- 17041850
TI - A live experimental vaccine against Burkholderia pseudomallei elicits CD4+ T cell
mediated immunity, priming T cells specific for 2 type III secretion system
proteins.
AB - Burkholderia pseudomallei is the etiological agent of melioidosis, a serious
human disease for which no vaccine is available. Immunization of susceptible
BALB/c mice with the live attenuated mutant B. pseudomallei ilvI (referred to as
"2D2") generated significant, although incomplete, immunity. Splenic B.
pseudomallei-specific T cells, detected in immunized mice, proliferated and
produced interferon-gamma in vitro in response to dead bacteria. Assessment of T
cell antigen specificity indicated that subpopulations of B. pseudomallei
reactive T cells were responsive to BopE, a type III secretion system (TTSS)
effector protein, and to a lesser extent to BipD, a TTSS translocator protein.
Increased survival of severe combined immunodeficient mice adoptively transferred
with T cells from immunized mice, compared with that of naive T cell recipients,
demonstrated that immunization with 2D2 generated T cell-mediated immunity. CD4+
and CD8+ cell depletion studies demonstrated that CD4+ cells, but not CD8+ cells,
mediated this protection in vivo. Thus, CD4+ T cells can mediate vaccine-induced
immunity to experimental melioidosis.
PMID- 17041849
TI - Deletion of a Mycobacterium tuberculosis proteasomal ATPase homologue gene
produces a slow-growing strain that persists in host tissues.
AB - The in vivo rate of proliferation of Mycobacterium tuberculosis, the causative
agent of tuberculosis, has been linked to the rate of progression and severity of
disease. Here, we report that deletion of the gene MT2175 (Rv2115c), a putative
mycobacterial proteasome-associated AAA-ATPase, leads to a reduction in the
growth rate of M. tuberculosis in vitro and in vivo. Despite the reduced growth,
the mutant persisted, with slow and gradual clearance in mouse lungs. The mutant
elicited reduced levels of interferon-gamma production in the lungs and, when
used as an immunizing agent, provided significant protection against challenge
with a virulent strain of M. tuberculosis. Expression of the genes lat and MT3159
were highly up-regulated in the mutant. Thus, loss of MT2175 slows both in vitro
and in vivo growth rates and compromises the lethality of M. tuberculosis in mice
but has a minimal impact on the organism's ability to persist in host tissues.
PMID- 17041851
TI - Protective immunity against respiratory tract challenge with Yersinia pestis in
mice immunized with an adenovirus-based vaccine vector expressing V antigen.
AB - The aerosol form of the bacterium Yersinia pestis causes the pneumonic plague, a
rapidly fatal disease. At present, no plague vaccines are available for use in
the United States. One candidate for the development of a subunit vaccine is the
Y. pestis virulence (V) antigen, a protein that mediates the function of the
Yersinia outer protein virulence factors and suppresses inflammatory responses in
the host. On the basis of the knowledge that adenovirus (Ad) gene-transfer
vectors act as adjuvants in eliciting host immunity against the transgene they
carry, we tested the hypothesis that a single administration of a replication
defective Ad gene-transfer vector encoding the Y. pestis V antigen (AdsecV) could
stimulate strong protective immune responses without a requirement for repeat
administration. AdsecV elicited specific T cell responses and high IgG titers in
serum within 2 weeks after a single intramuscular immunization. Importantly, the
mice were protected from a lethal intranasal challenge of Y. pestis CO92 from 4
weeks up to 6 months after immunization with a single intramuscular dose of
AdsecV. These observations suggest that an Ad gene-transfer vector expressing V
antigen is a candidate for development of an effective anti-plague vaccine.
PMID- 17041852
TI - Identification of CT521 as a frequent target of Th1 cells in patients with
urogenital Chlamydia trachomatis infection.
AB - BACKGROUND: The human immune response to a Chlamydia trachomatis serovar D lysate
was investigated in patients with urogenital C. trachomatis infection, to
identify novel T cell targets. METHODS: A C. trachomatis lysate was fractionated
on the basis of molecular mass, and each fraction was used to stimulate
peripheral-blood mononuclear cells from patients with C. trachomatis infection.
In frequently recognized fractions, proteins were identified by mass
spectrometry, recombinantly expressed, and tested for T cell recognition.
RESULTS: T cell recognition of the fractions was highly heterogeneous in patients
with C. trachomatis infection (n=16). Four patients exhibited responses that were
strongly targeted to antigens of 16-20-kDa molecular mass. Three proteins were
identified in this fraction: CT043, CT511, and CT521. The T cell response to the
individual recombinant proteins were investigated, and CT521 was found to induce
the highest level of interferon (IFN)- gamma. The recognition of CT521 was
investigated in a larger study population (n=41), and a positive IFN-gamma
response was measured in 83% of the patients. Several T cell epitopes were
identified in CT521; in particular, peptide 5 in the central part of the protein
was frequently recognized by T cells (63%). CONCLUSION: We have identified a
novel C. trachomatis antigen, CT521, that is frequently recognized in patients
with urogenital C. trachomatis infection.
PMID- 17041853
TI - Regulation of Staphylococcus aureus alpha-toxin gene (hla) expression by agr,
sarA, and sae in vitro and in experimental infective endocarditis.
AB - BACKGROUND: The Staphylococcus aureus global regulators--agr, sarA, and sae-
coordinately control alpha-toxin gene (hla) expression in vitro. However, their
relative in vivo contributions to hla expression, particularly in endovascular
infections, have not been defined. METHODS: A plasmid-based hla-promoter:green
fluorescent protein reporter system was constructed in 2 genetically related S.
aureus strains: RN6390 (a natural sigma factor B [sigB]-deficient mutant), SH1000
(a sigB-repaired variant of RN6390 lineage), and their respective agr, sarA,
agr/sarA, and sae mutants. These strain sets were used to quantify hla expression
in vitro and in an experimental infective endocarditis (IE) model using flow
cytometry. RESULTS: In vitro, hla expression was positively modulated by all 3
regulons (sae > agr/sarA > agr and sarA) in both RN6390 and SH1000 backgrounds.
In the IE model, hla expression in cardiac vegetations was lower in all single
mutants than in the respective parental strains (P<.05 for sae mutant) but was
maintained at near-parental levels in the agr/sarA double mutant in both
backgrounds. A similar finding was also observed in kidneys and spleens.
CONCLUSIONS: These results indicate that, although several distinct regulatory
circuits can affect hla expression in vitro and in vivo, sae appears to play a
crucial role in this context.
PMID- 17041854
TI - Human bocavirus infection in young children in the United States: molecular
epidemiological profile and clinical characteristics of a newly emerging
respiratory virus.
AB - BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus that
was originally identified in the respiratory secretions of children with
respiratory tract disease. To further investigate the epidemiological profile and
clinical characteristics of HBoV infection, we screened infants and children <2
years of age (hereafter referred to as "children") for HBoV. METHODS: Children
for whom respiratory specimens submitted to a diagnostic laboratory tested
negative for respiratory syncytial virus, parainfluenza viruses (types 1-3),
influenza A and B viruses, and adenovirus, as well as asymptomatic children,
underwent screening for HBoV by use of polymerase chain reaction (PCR).
Respiratory specimens were obtained from the children from 1 January 2004 through
31 December 2004. RESULTS: Twenty-two (5.2%) of the 425 children who had a
respiratory specimen submitted to the diagnostic laboratory and 0 of the 96
asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever,
rhinorrhea, cough, and wheezing were observed in > or =50% of the HBoV-positive
children. Of the 17 children who had chest radiography performed, 12 (70.6%) had
abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide
polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two
distinct HBoV genotypes circulated during the study period. CONCLUSIONS: HBoV is
circulating in the United States and is associated with both upper and lower
respiratory tract disease in infants and young children.
PMID- 17041855
TI - Epidemiological profile and clinical associations of human bocavirus and other
human parvoviruses.
AB - BACKGROUND: Human bocavirus (HBoV) and PARV4 are newly discovered human
parvoviruses. HBoV, which was first detected in respiratory samples, has a
potential role in the development of human respiratory disease. The present study
compared the frequencies, epidemiological profiles, and clinical backgrounds of
HBoV and PARV4 infections with those of other respiratory virus infections, by
evaluating diagnostic samples referred to the Specialist Virology Laboratory
(SVL) at the Royal Infirmary of Edinburgh (Edinburgh, United Kingdom). METHODS:
Anonymized samples and study subject information were obtained from the
respiratory sample archive of the SVL. Samples were screened for HBoV, PARV4,
B19, respiratory syncytial virus (RSV), adenoviruses, influenza viruses, and
parainfluenza viruses by use of nested polymerase chain reaction. RESULTS: HBoV
infection was detected in 47 (8.2%) of 574 study subjects, ranking third in
prevalence behind RSV infection (15.7%) and adenovirus infection (10.3%). Peak
incidences of HBoV were noted among infants and young children (age, 6-24 months)
during the midwinter months (December and January) and were specifically
associated with lower respiratory tract infections. HBoV infections were
frequently accompanied by other respiratory viruses (frequency, 43%), and they
were more prevalent among individuals infected with other respiratory viruses
(17%), frequently adenovirus or RSV. All respiratory samples were negative for
PARV4. CONCLUSIONS: In the present study, HBoV was a frequently detected,
potential respiratory pathogen, with a prevalence and an epidemiological profile
comparable to those of RSV. Identification of HBoV infections may be clinically
important in the future.
PMID- 17041856
TI - Human papillomavirus genotypes and the cumulative 2-year risk of cervical
precancer.
AB - BACKGROUND: Prospective data on the risks of cervical precancer associated with
specific human papillomavirus (HPV) genotypes are limited. METHODS: In 5060 women
participating in the Atypical Squamous Cells of Undetermined Significance/Low
Grade Squamous Intraepithelial Lesions Triage Study (ALTS), we determined the
cumulative 2-year risks of cervical intraepithelial neoplasia (CIN) grade 2 or
more severe (> or =CIN2) and of grade 3 or more severe (> or =CIN3) for 38
individual HPV genotypes, as detected by polymerase chain reaction. RESULTS: The
most common HPV genotypes detected at baseline, in descending order of
prevalence, were 16, 52, 51, 31, 18, 53, 39, 56, 62, 59, and 58. When detected as
a single-type HPV infection, HPV-16 had a 2-year cumulative risk of 50.6% (95%
confidence interval [CI], 44.1%-57.2%) for > or =CIN2 and 39.1% (95% CI, 32.9%
45.7%) for > or =CIN3. For other singly detected carcinogenic HPV types, the risk
of > or =CIN2 ranged from 4.7% (for HPV-59) to 29.5% (for HPV-31), and the risk
of > or =CIN3 ranged from 0.0% (for HPV-59) to 14.8% (for HPV-31). Multiple
infections with HPV genotypes of different risk classes resulted in a risk that
was similar to, and not significantly different from, the risk observed for the
HPV genotype of the highest risk class. CONCLUSIONS: Genotype-specific HPV
testing may be useful for identifying women with atypical squamous cells of
undetermined significance and low-grade squamous intraepithelial lesions who are
at higher and lower risk of prevalent and incipient cervical precancer.
PMID- 17041857
TI - Humanized monoclonal antibody against West Nile virus envelope protein
administered after neuronal infection protects against lethal encephalitis in
hamsters.
AB - Humans infected with West Nile virus (WNV) may clinically present with symptoms
that are suggestive of neurological infection. Nearly all treatments of WNV
disease have been effective in animal models only if administered before or soon
after viral challenge. Here, we evaluated whether a potent neutralizing anti-WNV
humanized monoclonal antibody (MAb), hE16, could improve the course of disease in
a hamster model when administered after the virus had infected neurons in the
brain. Five days after viral injection, WNV was detected in the brains of
hamsters by cytopathic assay, quantitative reverse-transcription polymerase chain
reaction, and immunohistochemical staining of WNV envelope in neurons. Notably,
80%-90% of the hamsters treated 5 days after viral injection by intraperitoneal
injection with hE16 survived the disease, compared with 37% of the placebo
treated hamsters (P< or =.001). The hamsters that received hE16 directly in the
brain also exhibited markedly improved survival rates, compared with those in the
placebo-treated hamsters. In prospective experiments, hamsters with high levels
of infectious WNV in their cerebrospinal fluid were also protected by hE16 when
administered 5 days after viral injection. These experiments suggest that
humanized MAbs with potent neutralizing activity are a possible treatment for
human patients after WNV has infected neurons in the central nervous system.
PMID- 17041858
TI - A randomized trial of treatment interruption before optimized antiretroviral
therapy for persons with drug-resistant HIV: 48-week virologic results of ACTG
A5086.
AB - BACKGROUND: The role of structured treatment interruption (STI) before optimized
antiretroviral therapy (ART) in patients with drug-resistant human
immunodeficiency virus type 1 (HIV-1) is uncertain. METHODS: AIDS Clinical Trial
Group protocol A5086 was a prospective trial of 41 patients with multiple drug
class-resistant HIV who were randomized to undergo a 16-week STI followed by
optimized ART (STI) or immediate optimized ART (no STI). The primary end point
was the proportion of subjects with HIV-1 RNA loads <400 copies/mL 48 weeks after
randomization. RESULTS: Of 39 evaluable patients, 4 (19%) in the STI arm and 6
(33%) in the no STI arm had HIV-1 RNA loads <400 copies/mL at 48 weeks (P=.44).
Median changes from baseline in CD4+ cell counts and HIV-1 RNA loads were similar
for both arms. Standard genotypes at the end of STI showed nearly complete
reversion to wild-type virus in a minority of patients (n=5; 28%). Virus with 3
drug class resistance reemerged even when ART included only 1 or 2 drug classes.
Single-genome sequencing showed that each genome encoded resistance mutations for
3 drug classes. CONCLUSIONS: A 16-week STI before optimized ART did not improve
virologic response. Genetic analyses strongly suggest that virologic failure
resulted from the reemergence of virus present before STI that encoded 3-drug
class resistance on the same genome.
PMID- 17041859
TI - Viral decay dynamics in HIV-infected patients receiving ritonavir-boosted
saquinavir and efavirenz with or without enfuvirtide: a randomized, controlled
trial (HIV-NAT 012).
AB - The availability of enfuvirtide enables assessment of whether human
immunodeficiency virus (HIV) decay can be enhanced by targeting reverse
transcriptase, protease, and fusion. We performed a 12-week study of 22 patients
randomized to receive ritonavir-boosted saquinavir and efavirenz with (the 3
target arm) or without (the 2-target arm) enfuvirtide. We observed no difference
in the mean+/-SD elimination-rate constant for overall decay (0.142+/-0.040 per
day and 0.128 +/- 0.033 per day in the 2- and 3-target arms, respectively; P>.1)
or for modeled first-phase decay rate (-0.62+/-0.34 per day and -0.51+/-0.16 per
day; P>.1). Antiretroviral therapy that inhibits HIV reverse transcriptase and
protease exerts potent antiviral effects that might not be augmented by the
addition of an HIV fusion inhibitor.
PMID- 17041860
TI - Epstein-Barr virus infects B and non-B lymphocytes in HIV-1-infected children and
adolescents.
AB - Epstein-Barr virus (EBV) is a widespread, persistent herpesvirus that can
transform B cells and that is associated with malignant lymphomas. EBV dynamics
and specific immunity in human immunodeficiency virus (HIV)-1-infected children
are unknown. We found that, in 74% of EBV-seropositive, HIV-1-infected children,
EBV DNA loads at the start of highly active antiretroviral therapy (HAART) were
comparable with those in acutely EBV-infected, HIV-negative children. EBV DNA
load remained elevated in most HIV-1-infected children for months to years of
follow-up. Frequencies of interferon-gamma-producing EBV-specific CD8+ T cells
were comparable with those in healthy control children, and antibodies to EBV
nuclear antigen were detected in 73% of EBV-seropositive children. Detectable EBV
DNA load was not correlated with HIV-1 RNA level or with CD4+ T cell count
increase after the start of HAART. Because of its resemblance to chronic active
EBV, we studied the cellular tropism of EBV in these patients. EBV DNA was found
not only in the CD19+ B cell fraction but also--at stable levels--in the CD4+ and
CD8+ T cell fractions. Although the reason for the aberrant T cell tropism of EBV
remains unclear, these data may provide an explanation for the differential EBV
dynamics in the presence of normal serological findings.
PMID- 17041861
TI - Early procoagulant shift in the bronchoalveolar compartment of patients with
secondary peritonitis.
AB - BACKGROUND: In acute respiratory distress syndrome or pneumonia, a procoagulant
shift is observed in bronchoalveolar lavage fluid (BALF). The effect of a
primarily extrapulmonary infection on coagulation and fibrinolysis in the
pulmonary compartment is unclear. METHODS: In 35 patients, 87 bronchoalveolar
lavages were performed on the day of operation for secondary peritonitis (day 0)
and on days 2 and 3 after surgery. Two noninfectious control groups were
included: subjects undergoing bronchoalveolar lavage after elective surgery (n=8)
and those undergoing long-term mechanical ventilation (n=10). RESULTS: In BALF
from patients with peritonitis, a tissue factor (TF)/factor VIIa-mediated
activation of coagulation was shown (high levels of thrombin-antithrombin
complexes). Levels of fibrinolysis activators decreased rapidly after day 0,
whereas levels of inhibitors increased. The net effect was reduced fibrinolysis
(plasminogen activator activity). The sequential comparison of plasma levels of
TF pathway inhibitor showed higher levels in patients who died (28-day mortality;
P<.001). Sequential levels of TF in BALF were higher in patients with low PaO2 :
FiO2 ratios (<200; P=.039). Differences between patients and control subjects
were more pronounced in BALF than in plasma. CONCLUSIONS: Secondary peritonitis
induces an early activation of the coagulation and inhibition of fibrinolysis in
the systemic and bronchoalveolar compartments, possibly via a compartmentalized
response. This imbalance may be associated with reduced oxygen delivery and an
adverse outcome in secondary peritonitis.
PMID- 17041863
TI - Elevated plasma levels of limulus amoebocyte lysate-reactive material.
PMID- 17041864
TI - Chloride uptake and base secretion in freshwater fish: a transepithelial ion
transport metabolon?
AB - Despite all the efforts and technological advances during the last few decades,
the cellular mechanisms for branchial chloride uptake in freshwater (FW) fish are
still unclear. Although a tight 1 : 1 link with HCO-3 secretion has been
established, not much is known about the identity of the ion-transporting
proteins involved or the energizing steps that allow for the inward transport of
Cl- against the concentration gradient. We propose a new model for Cl- uptake in
FW fish whereby the combined action of an apical anion exchanger, cytoplasmic
carbonic anhydrase, and basolateral V-type H+ -ATPase creates a local [HCO-3]
high enough to energize Cl- uptake. Our model is based on analyses of structure
function relationships, reinterpretation of previous results, and novel
observations about gill cell subtypes and immunolocalization of the V-H+ -ATPase.
PMID- 17041865
TI - The coupled evolution of breathing and locomotion as a game of leapfrog.
AB - Because the increase in metabolic rate related to locomotor activity places
demands on the cardiorespiratory apparatus, it is not surprising that the
evolution of breathing and of locomotion are coupled. As the respiratory faculty
becomes more refined, increasingly aerobic life strategies can be explored, and
this activity is in turn expedited by a higher-performance respiratory apparatus.
This apparent leapfrogging of respiratory and locomotor faculties begins in
noncraniate chordates and continues in water-breathing and air-breathing
vertebrates. Because both locomotor and cardiorespiratory activities are
coordinated in the brain, neurological as well as biochemical coupling is
evident. In spite of very different breathing mechanisms in various vertebrate
groups, the basic respiratory control mechanisms appear to have been conserved,
and respiratory-locomotor coupling is evident in all classes of vertebrates.
Hypaxial body wall muscles that were strictly locomotor in fish have respiratory
function in amniotes, but some locomotor function remains in all groups.
PMID- 17041866
TI - Coupling of the respiratory rhythm in fish with activity in hypobranchial nerves
and with heartbeat.
AB - Fish have a central respiratory pattern generator (CRPG) in the brain stem that
initiates activity in a series of cranial nerves innervating respiratory muscles.
These nerves burst sequentially in the order of their rostrocaudal distribution
in the central nervous system. When respiratory drive is high, this activity
spreads caudally to occipital and anterior spinal neurons that project via the
hypobranchial nerves to stimulate hypaxial muscles, causing active jaw abduction.
The CRPG may also recruit the heart. Fish, like mammals, show respiratory
components in the intrinsic variability of heart rate (HRV). Cardiorespiratory
synchrony in the dogfish is driven by bursting activity in the cardiac branches
of the vagus nerve, which emanates from preganglionic neurons in the dorsal vagal
motor nucleus. A respiratory component in HRV is difficult to discriminate in
other species, requiring the use of power spectral analysis and the subsequent
elimination of aliased components.
PMID- 17041867
TI - Lung and buccal ventilation in the frog: uncoupling coupled oscillators.
AB - The frog, with two distinct ventilatory acts, provides a useful model to
investigate the prospective interaction of two oscillators in generating the
respiratory rhythm. Building on evidence supporting the existence of separate
oscillators generating buccal and lung ventilation, we have attempted to uncouple
the two rhythms in the isolated brain stem preparation. Opioid preferentially
inhibits the lung rhythm, suggesting an uncoupling of the lung from the buccal
oscillator. Reduction of the superfusate chloride concentration alters both the
buccal and the lung rhythms. Joint application of opioid and reduced-chloride
superfusate leads to an increase in the variability of the buccal burst-to-lung
burst intervals. This increase in variability suggests that chloride-mediated
mechanisms are involved in coupling the buccal oscillator to the lung oscillator.
Given the results from these interventions, we propose a simple schematic model
of the frog respiratory rhythm generator, outlining the coupling of the lung and
buccal oscillators.
PMID- 17041868
TI - Function of intracoelomic septa in lung ventilation of amniotes: lessons from
lizards.
AB - Aspiration breathing is the dominant mechanism of lung inflation among extant
amniotes. However, aspiration has two fundamental problems associated with it:
paradoxical visceral translation and partial lung collapse. These can constrain
the inspiratory tidal volume, reduce the effective lung ventilation, and
ultimately curtail the aerobic capacity of an animal. Separation of the pleural
and peritoneal cavities by an intracoelomic septum can restrict the cranial shift
of abdominal viscera and provide structural support to the caudal lung surface. A
muscular septum, such as the diaphragm of mammals or the diaphragmaticus of
crocodilians, can exert active control over visceral translation and the degree
of lung inflation. To a lesser degree, a nonmuscular septum can also function as
a passive barrier when stretched taut by rib rotation. Studies of the posthepatic
septum in teiid lizards and the postpulmonary septum in varanid lizards
underscore the importance of nonmuscular septa in aspiration. These septa provide
plausible functional models that help us infer the evolution of mammalian and
avian lung ventilatory systems, respectively.
PMID- 17041869
TI - Effects of the natural tidal cycle and artificial temperature cycling on Hsp
levels in the tidepool sculpin Oligocottus maculosus.
AB - The rocky intertidal zone is characterized by a predictable cycle of
environmental change cued by the ebb and flow of the tides. Tidepools are thus an
excellent environment in which to determine whether predictability of
environmental change can entrain an endogenous rhythmicity in heat shock protein
(Hsp) levels. In this study, we monitored changes in Hsp mRNA and protein levels
that occurred over the tidal cycle in tidepool sculpins and investigated whether
there was an endogenous tidal rhythm in Hsp expression that persisted once the
sculpins were transferred to a stable environment. Fluctuations in the tidepool
environment increased hsc70, hsp70, and hsp90 mRNA levels, which translated into
increased Hsc/Hsp70 and Hsp90 protein levels; however, this was not due to an
endogenous tidal rhythm in Hsp levels because sculpins held under constant
conditions did not show any rhythmicity in the expression of these genes. By
exposing sculpins to an artificial temperature cycling regime that mimicked the
temperature changes of a mid-intertidal pool, we were able to account for the
direct role of temperature in regulating Hsp expression. However, there are
additional extrinsic factors that likely integrate with temperature and result in
differences between the hsp induction profiles that were observed in sculpins
inhabiting their natural environment and those in cycling conditions in the
laboratory.
PMID- 17041870
TI - Swimming performance, metabolic rates, and their correlates in the Iceland
scallop Chlamys islandica.
AB - The dramatic escape response of some scallops is modified by reproductive
investment and by acclimation temperature. Despite considerable knowledge of the
physiology of the escape response, functional links between escape response
performance, organismal rates of oxygen uptake, and tissue metabolic capacities
are little known. We measured oxygen consumption rates (standard, maximal, and
aerobic scope), escape behavior (initial and repeat performance), tissue mass,
condition index, protein content, and tissue metabolic capacities in the Iceland
scallop Chlamys islandica to examine links between these parameters. Postexercise
oxygen consumption rates were positively linked to contraction rate (repeat test)
and to pyruvate kinase activity in the adductor muscle but negatively linked to
digestive gland wet mass. Swimming behavior was mainly related to activity of
glycolytic enzymes, and enzymatic activities were related to anatomic parameters.
Scallop behavior and physiology change with size, both within our samples and on
a larger scale. Small scallops showed more intense swimming activity and had
higher arginine kinase activities but lower glycolytic enzyme activities in their
adductor muscle than larger scallops. This corresponds to the ontogenetic change
in susceptibility to predation and in habitat use observed in C. islandica.
PMID- 17041871
TI - Wiping behavior, skin resistance, and the metabolic response to dehydration in
the arboreal frog Phyllomedusa hypochondrialis.
AB - Several species of arboreal frogs secrete lipids from cutaneous glands and wipe
these secretions over the body surfaces to reduce evaporative water losses.
Following wiping, frogs become immobile in water-conserving postures, and some
have suggested they are torpid. Here we report wiping behaviors and the
physiological correlates of immobile postures in the arboreal monkey frog
Phyllomedusa hypochondrialis. Skin resistance to water loss was comparatively
high, and rates of evaporation were as low as 4% of that from a free water
surface. Standard rates of metabolism (SMR) varied from 89 microL O2 h(-1) at 18
degrees C to 316 microL O2 h(-1) at 34 degrees C and were sensitive to both
temperature (T) and body mass (W; mL O2 h(-1) = 0.016W0.642 x 10(0.030T)). The
mean SMR did not change significantly during four consecutive days of dehydration
when animals lost 19%-34% of body mass. Therefore, it appears these frogs do not
routinely depress metabolic rates following wiping. However, some individuals
that lost higher percentages of body water exhibited trends of decreasing oxygen
consumption, suggesting that suppression of metabolic rates might occur at
greater levels of body water deficit or perhaps during a slower course of
dehydration than imposed by our experiments (e.g., individuals that are secluded
during periods of drought).
PMID- 17041872
TI - Influence of the nest environment on bone mineral content in hatchling painted
turtles (Chrysemys picta).
AB - We performed an experiment at a field site in north-central Nebraska to assess
the role of the nest environment in inducing variation in bone mineral content in
hatchling painted turtles Chrysemys picta (Schneider 1783). The contents of
several newly constructed nests were manipulated by reciprocal transplant, after
which the eggs were allowed to incubate for 8 wk under natural conditions. The
nests were then excavated, and the eggs were brought into the laboratory to
complete incubation and hatch under standard conditions of temperature and
moisture. The hatchlings were killed, and their carcasses and residual yolks were
analyzed separately for calcium and phosphorus. More of the random variation in
carcass calcium and phosphorus was related to the nest in which eggs incubated
(37% and 42%, respectively) than was associated with the clutch of origin (21%
and 37%). Moreover, hatchlings from some nests contained substantially more
calcium and phosphorus than did hatchlings from other nests, both in terms of the
absolute amounts of the elements in their carcasses (pointing to variation in
body size) and in terms of the concentrations of those elements (pointing to
variation in bone density). The amounts of calcium and phosphorus in carcasses of
hatchlings were positively correlated with changes in mass of their eggs during
the 8 wk that the eggs incubated in nests in the field, thereby indicating that
the influence of the nest environment on developing embryos probably was mediated
by water exchanges experienced by the eggs. These findings indicate that
developmental plasticity underlies a major fraction of the variation in mineral
content of hatchling painted turtles emerging from nests in the field. Phenotypic
variation attributable to plasticity consequently needs to be addressed in models
for life-history evolution of painted turtles and other chelonians producing eggs
with soft, flexible shells.
PMID- 17041874
TI - Physiological response to feeding in little penguins.
AB - Specific dynamic action (SDA), the increase in metabolic rate above resting
levels that accompanies the processes of digestion and assimilation of food, can
form a substantial part of the daily energy budget of free-ranging animals. We
measured heart rate (fH) and rate of oxygen consumption (VO2) in 12 little
penguins while they digested a meal of sardines in order to determine whether
they show specific dynamic action. In contrast to some studies of other penguin
species, little penguins showed a substantial SDA, the magnitude of which was
proportional to the size of the meal. The energy utilized in SDA was equivalent
to 13.4% of the available energy content of the fish. Furthermore, animals such
as penguins that forage in a cold environment will probably expend further energy
in heating their food to body temperature to facilitate efficient digestion. It
is estimated that this additional energy expenditure was equivalent to 1.6%-2.3%
of the available energy content of the fish, depending on the time of year and
therefore the temperature of the water. Changes in fH during digestion were
qualitatively similar to those in VO2, implying that there were no substantial
circulatory adjustments during digestion and that the relationship between fH and
VO2 in penguins is unaffected by digestive state.
PMID- 17041873
TI - Hummingbirds fuel hovering flight with newly ingested sugar.
AB - We sought to characterize the ability of hummingbirds to fuel their energetically
expensive hovering flight using dietary sugar by a combination of respirometry
and stable carbon isotope techniques. Broadtailed hummingbirds (Selasphorus
platycercus) were maintained on a diet containing beet sugar with an isotopic
composition characteristic of C3 plants. Hummingbirds were fasted and then
offered a solution containing cane sugar with an isotopic composition
characteristic of C4 plants. By monitoring the rates of CO2 production and O2
consumption, as well as the stable carbon isotope composition of expired CO2, we
were able to estimate the relative contributions of carbohydrate and fat, as well
as the absolute rate at which dietary sucrose was oxidized during hovering. The
combination of respirometry and carbon isotope analysis revealed that
hummingbirds initially oxidized endogenous fat following a fast and then
progressively oxidized proportionately more carbohydrates. The contribution from
dietary sources increased with each feeding bout, and by 20 min after the first
meal, dietary sugar supported approximately 74% of hovering metabolism. The
ability of hummingbirds to satisfy the energetic requirements of hovering flight
mainly with recently ingested sugar is unique among vertebrates. Our finding
provides an example of evolutionary convergence in physiological and biochemical
traits among unrelated nectar-feeding animals.
PMID- 17041875
TI - Yolk antioxidants vary with male attractiveness and female condition in the house
finch (Carpodacus mexicanus).
AB - The manipulation of egg content is one of the few ways by which female birds can
alter offspring quality before hatch. Lipid-soluble vitamins and carotenoids are
potent antioxidants. Female birds deposit these antioxidants into eggs in
variable amounts according to environmental and social conditions, and the
quantities deposited into eggs can have effects on offspring health and
immunological condition. Allocation theory posits that females will alter the
distribution of resources according to mate quality, sometimes allocating
resources according to the differential allocation hypothesis (DAH), investing
more in offspring sired by better-quality males, and other times allocating
resources according to a compensatory strategy, enhancing the quality of
offspring sired by lower-quality males. It is unknown, however, whether
antioxidants are deposited into eggs according to the DAH or a compensatory
strategy. We examined deposition patterns of yolk antioxidants (including vitamin
E and three carotenoids) in relation to laying order, mate attractiveness, female
condition, and yolk androgen content in the house finch (Carpodacus mexicanus).
Female house finches deposited significantly more total antioxidants into eggs
sired by less attractive males. Additionally, yolk antioxidant content was
significantly positively correlated with female condition, which suggests a cost
associated with the deposition of antioxidants into eggs. Finally, concentrations
of antioxidants in egg yolks were positively correlated with total yolk androgen
content. We suggest that yolk antioxidants are deposited according to a
compensatory deposition strategy, enabling females to improve the quality of
young produced with less attractive males. Additionally, yolk antioxidants may
act to counter some of the detrimental effects associated with high levels of
yolk androgens in eggs and, thus, may exert a complementary effect to yolk
androgens.
PMID- 17041876
TI - Angiotensin II and aldosterone increase with fasting in breeding adult male
northern elephant seals (Mirounga angustirostris).
AB - The renin-angiotensin-aldosterone system (RAAS) appears to contribute
significantly to osmoregulation of fasting northern elephant seal (Mirounga
angustirostris) pups; however, RAAS has not been characterized in fasting adult
seals. Therefore, this study examined the contribution of RAAS to water turnover
rates in fasting adult male northern elephant seals. Blood samples were obtained
twice during their breeding fast at an interval of 6.5 wk, and water efflux rate
was estimated by isotopic dilution during the same period. Serum electrolytes
(Na+, K+, Cl-) and osmolality were unaltered between the two sampling periods,
indicating ionic and osmotic homeostasis during the fast. Despite the lack of an
increase in vasopressin, serum angiotensin II and aldosterone were increased and
were significantly and positively correlated. Changes in aldosterone
concentration and water efflux rate were significantly and negatively correlated,
suggesting that the greater the increase in aldosterone, the smaller the loss of
water. Adult male seals maintain ionic and osmotic homeostasis similar to that of
fasting weaned pups, and this homeostasis appears to be mediated, at least in
part, by RAAS, which probably contributes to increased water retention as well.
The hormonal mechanisms by which northern elephant seals maintain water and
electrolyte balance during fasting conditions appear to be similar regardless of
age.
PMID- 17041877
TI - Determination of the mutation spectrum of the EXT1/EXT2 genes in British
Caucasian patients with multiple osteochondromas, and exclusion of six candidate
genes in EXT negative cases.
AB - We describe here the spectrum and distribution of mutations in the EXT1 and EXT2
genes in the largest reported British Caucasian multiple osteochondromas (MO)
population. Furthermore, we report for the first time the screening of the EXT1
and EXT2 promoters, 5'UTRs, and 3'UTRs, and exclude six potential MO candidate
genes in individuals without a detectable mutation within the coding region of
EXT1 and EXT2. The coding exons of EXT1 and EXT2 were screened in 72 unrelated
probands affected with MO. Forty-six different mutations were identified in 56
probands, of which 29 were novel. Mutation in the EXT1 and EXT2 genes each
accounted for 50% of the mutations identified. Of the 72 probands, 42 were of
British Caucasian descent, which when added to the 41 British Caucasian families
previously reported from our total cohort, gave a total of 83 families. This
cohort's proportional frequency for EXT1/EXT2 mutation was 53%/47%. We also
validated the technique of high-resolution melting analysis in a blind study
using 27 unique EXT1 or EXT2 mutations. This technique was found to be sensitive
with a detection rate of 100% regarding heterozygote detection for EXT mutation
scanning. Furthermore, this technique has a very high throughput and is very cost
effective.
PMID- 17041879
TI - Autocalibrating parallel imaging of in vivo trabecular bone microarchitecture at
3 Tesla.
AB - In this work the generalized autocalibrating partially parallel acquisition
(GRAPPA) technique was implemented with modified reconstruction and applied to in
vivo high-resolution (HR) magnetic resonance imaging (MRI) of the trabecular bone
microarchitecture at 3 Tesla (T) with a multiple-acquisition balanced steady
state free precession (b-SSFP) sequence. Trabecular bone is made up of a network
of microstructures (80-140 microm), and its structural deterioration is
associated with the skeletal metabolic disorder osteoporosis. HR-MRI is a
promising noninvasive tool for assessing the trabecular microarchitecture in
vivo, but it involves long acquisition times. Using partially parallel imaging
(PPI) to accelerate the acquisition may help mitigate this shortcoming and allow
more flexibility in protocol design. In this study the effects of GRAPPA-based
reconstruction on image characteristics and the measurement of trabecular bone
structural parameters were evaluated. Initial studies showed that image quality
and depiction of microstructure were preserved in the GRAPPA-based
reconstruction, indicating the feasibility of PPI in HR-MRI of trabecular bone.
The results also demonstrated the potential of PPI for increasing the signal-to
noise ratio (SNR) efficiency of multiple-acquisition b-SSFP imaging protocols.
PMID- 17041880
TI - How many nuclei make an embryo sac in flowering plants?
AB - Research on early-divergent angiosperms, including Amborella, the putative sister
to all other extant angiosperms, is increasingly used as a yardstick to infer the
nature of the hypothetical ancestral angiosperm. Some traits are relatively
diverse (and hence relatively labile) in this phylogenetic grade, compared with
the more derived eudicot clade, in which developmental patterns have become
increasingly canalized. One of the many mysteries surrounding the origin of the
angiosperms is the evolutionary origin of the Polygonum-type embryo sac
(monosporic, eight-nucleate and seven-celled) that occurs in the majority of
flowering plants. Observations on the megagametophyte of Amborella are
conflicting, but a recent report of a supernumerary synergid in this genus raises
the question of whether the Polygonum-type embryo sac is derived by duplication
of a four-nucleate structure or by reduction from a multicellular structure.
PMID- 17041881
TI - Concerning the preparation and use of substances with a magnetic susceptibility
equal to the magnetic susceptibility of air.
AB - In this work it is demonstrated that the susceptibility of diamagnetic
substances, such as water and agarose gel, can easily be tuned to the
susceptibility of air by the addition of a proper amount of strongly paramagnetic
ions, in this case 16.6 +/- 0.1 mM holmium(III). The resultant air-equivalent
substances are shown to allow the creation of objects that do not disturb the
static magnetic field of the scanner and hence do not invoke susceptibility
artifacts, regardless of the objects' shape, size, and orientation with respect
to B(0), and regardless of the pulse sequence being used. The addition of the
proper amount of holmium(III) to aqueous solutions and gels is further shown to
exert a negligible influence on the chemical shift and to cause a moderate
increase of the relaxation rates 1/T(1) and 1/T(2). The results indicate the
potential of air-equivalent substances for many purposes, including construction
of artifact-free test objects; experimental setups and accessory devices;
investigation of systems that contain air cavities, gas bubbles, etc.; and
monitoring of system-related and object-induced field disturbances.
PMID- 17041884
TI - Survival of men with clinically localized prostate cancer treated with
prostatectomy, brachytherapy, or no definitive treatment: impact of age at
diagnosis.
AB - BACKGROUND: The optimal treatment for men with early stage prostate cancer
remains undefined. Survival of such patients after surgery, brachytherapy, or no
definitive therapy was investigated specifically to determine the impact of age
at diagnosis. METHODS: In all, 60,290 men diagnosed with organ-confined, low and
moderate grade prostate cancer between 1988 and 2002 were retrospectively
identified from centers participating in the National Cancer Institute's
Surveillance, Epidemiology, and End Results (SEER) Program. Prostate cancer
specific mortality (PCSM) and any-cause mortality (ACM) were determined. Outcomes
for patients treated by brachytherapy, surgery, or receiving no definitive
treatment were compared using the Wilcoxon test, stratified by T-stage and grade,
and using multivariate analysis. RESULTS: The median follow-up time was 46 months
(range, 0-189 months). For men under age 60 at diagnosis, PCSM at 10 years was
1.3%, 0.5%, and 3.7% for surgery, brachytherapy, and no definitive therapy,
respectively. For men age 60 and older the PCSM was 3.8%, 5.3%, and 8.4%,
respectively. On univariate and multivariate analysis, surgery and brachytherapy
resulted in statistically equivalent PCSM and ACM, and both had a significantly
lower PCSM and ACM versus no definitive therapy. CONCLUSIONS: A better survival
was observed in men treated with a definitive therapy. The magnitude of the
benefit on PCSM or ACM was similar for both definitive therapies irrespective of
age.
PMID- 17041885
TI - Silencing the receptor EphA2 suppresses the growth and haptotaxis of malignant
mesothelioma cells.
AB - BACKGROUND: The over-expression of the ephrin-A1 ligand receptor EphA2 is
associated with the growth and metastatic potential of tumors. Although EphA2 is
expressed in a variety of tumors, its expression and function in malignant
mesothelioma (MM) remain unknown. The authors hypothesized that expression of the
receptor EphA2 in MM cells (MMCs) plays a key role in the growth and haptotactic
migration of MM. They also hypothesized that silencing EphA2 expression by using
small-interfering RNA (siRNA) inhibits the proliferation and haptotaxis of MMCs
and induces apoptosis in MMCs. METHODS: The expression of EphA2 in MMCs and in
normal pleural mesothelial cells (PMCs) was studied by using real-time
quantitative polymerase chain reaction analysis and Western blot analysis. The
growth of MMCs was determined with the WST-1 cell-proliferation assay. The
haptotactic migration of MMCs and PMCs was determined with a Boyden chamber
assay. Expression of caspases was determined with calorimetric assays. RESULTS:
The results demonstrated that silencing the receptor EphA2 by siRNA significantly
reduced the proliferation and haptotactic migration of MMCs compared with
controls. Over-expression of EphA2 with plasmid pcDNA/EphA2 enhanced the
proliferation and haptotaxis of MMCs significantly. Knocking down EphA2
expression initiated caspase-9-mediated apoptosis in MMCs. CONCLUSIONS: The
current results suggested that constitutive expression of EphA2 may contribute to
the aggressive behavior and cellular survival of MMCs. EphA2 may be an effective
therapeutic target in patients with mesothelioma. Silencing the receptor EphA2
gene is a novel approach for the containment of growth and migration of tumor in
patients with malignant mesothelioma.
PMID- 17041886
TI - Comparison of mRNA abundance quantified by gene expression profiling and
percentage of positive cells using immunophenotyping for diagnostic antigens in
acute and chronic leukemias.
AB - BACKGROUND: Microarray analysis is considered a future diagnostic tool in
leukemias. Whereas data accumulate on specific gene expression patterns in
biologically defined leukemia entities, data on the correlation between flow
cytometrically determined protein expression, which are essential in the
diagnostic setting today, and microarray results are limited. METHODS: The
results obtained by microarray analysis were compared using the Affymetrix
GeneChip HG-U133 system in parallel with flow cytometric findings of 36 relevant
targets in 814 patients with newly diagnosed acute and chronic leukemias as well
as in normal bone marrow samples. RESULTS: In a total of 21,581 individual
comparisons between signal intensities obtained by microarray analysis and
percentages of positive cell as determined by flow cytometry, coefficients of
correlation in the range of 0.171 to 0.807 were obtained. In particular, the
degree of correlation was high in the following genes critical in the diagnostic
setting: CD4, CD8, CD13 (ANPEP), CD33, CD23 (FCER2), CD64 (FCGR1A), CD117 (KIT),
CD34, MPO, CD20 (MS4A1), CD7 (range of r, 0.589-0.807). CONCLUSIONS: The present
data prove the high degree of correlation between findings obtained by microarray
analysis and flow cytometry. They are in favor of a future application of the
microarray technology as a robust diagnostic tool in leukemias.
PMID- 17041887
TI - Standardization of pelvic lymphadenectomy performed at radical cystectomy: can we
establish a minimum number of lymph nodes that should be removed?
AB - BACKGROUND: The number of lymph nodes (LNs) removed during radical cystectomy
(RC) for transitional cell carcinoma (TCC) of the bladder affects overall and
disease-specific survival, but no consensus exists regarding the minimum number
of LNs that should be removed. The goal of the current study was to determine if
a threshold number of nodes exists, above which taking additional LNs has no
clinical benefit. METHODS: A total of 1121 patients were identified who underwent
RC for clinically localized TCC of the bladder between January 1990 and April
2004. To determine the relation of LNs removal and overall survival, a Cox
proportional hazards model was used with pathologic stage, age, and comorbidity
as covariates. A dose-response curve, adjusted for covariates, was modeled to
assess the impact of an increasing number of LNs removed on overall survival.
RESULTS: A median of 9 LNs were removed (range, 0-53 LNs). In multivariable
analysis, all covariates (number of LNs removed, age, stage of disease, and
comorbidity) were found to be predictive of survival. The dose-response curve for
number of LNs versus survival revealed that, when adjusted for covariates, the
probability of survival did not plateau but instead continued to rise as the
number of LNs removed increased. CONCLUSIONS: No evidence was found that a
minimum number of LNs is sufficient for optimizing bladder cancer outcomes when a
limited or extended pelvic LN dissection is performed during RC. Instead, the
probability of survival continues to rise as the number of LNs removed increases.
This study supports a more extended LN dissection at the time of RC, and
highlights the challenges of interpreting retrospective LN dissection data.
PMID- 17041888
TI - Cotreatment with a novel phosphoinositide analogue inhibitor and carmustine
enhances chemotherapeutic efficacy by attenuating AKT activity in gliomas.
AB - BACKGROUND: Heightened activity of the AKT signaling pathway is prominent in
malignant gliomas and has been suggested to play a role in treatment resistance.
Selective targeting of AKT, therefore, may increase chemosensitivity. Recently, a
novel class of AKT-selective inhibitors has been described, including SH-6, a
phosphatidylinositol analogue. METHODS: The effects of SH-6 on AKT signaling were
tested in glioma cells, and the putative role of AKT signaling in chemoresistance
was tested by attenuating AKT signaling pharmacologically and genetically. The
initial characterization of SH-6 included treatment of glioma cells with
increasing doses of SH-6 (0.30-30 microM) and examining the effects on AKT
signaling proteins by Western blot analyses and in kinase assays with
immunoprecipitated AKT1. Dose-response studies with SH-6 administered to glioma
cell lines were performed using a luminescent cell-viability assay (0.1-30
microM). Studies examining the effect of carmustine, either alone or in
combination with either the phosphatidylinositol 3-kinase inhibitor LY294002 or
SH-6, were performed by cell viability assays and clonogenic survival assays. The
effect of carmustine on AKT activity as a response to treatment also was
examined. Caspase assays were used to examine the potential role of apoptosis in
SH-6/ carmustine -elicited cell death. Finally, the induction of a dominant
negative AKT1 transgene was used in combination with carmustine to demonstrate
the role of AKT1 in carmustine chemoresistance. RESULTS: Serum-stimulated
phosphorylation of AKT1 was inhibited by SH-6 at doses > or =10 microM (>70%
decrease in Threonine 308 and Serine 473 phosphorylation of AKT1). In adenosine
triphosphate assays, 72 hours of treatment with SH-6 led to 50% lethal doses near
10 microM for 2 cell lines tested. SH-6 enhancement of carmustine-mediated cell
death led to synergistic increases in Caspase 3/Capsase 7 activity, implicating
apoptosis as the cell death mechanism. In clonogenic assays, SH-6 cotreatment
with carmustine significantly decreased the number of colonies at 10 microM (P <
.05) compared with carmustine alone. No decrease was observed in cells that were
treated with SH-6 alone (10 microM). LY294002 (10 microM) was also able to
enhance the effects of carmustine significantly in both cell lines. CONCLUSIONS:
In the current study, the authors characterized the efficacy of a new class of
adjuvant chemotherapeutics that show promise in enhancing the efficacy of
standard chemotherapy regimens in gliomas.
PMID- 17041889
TI - Recessive arrhythmogenic right ventricular dysplasia due to novel cryptic splice
mutation in PKP2.
AB - Arrhythmogenic right ventricular dysplasia (ARVD) is a genetic disorder resulting
in fibro-fatty replacement of right ventricular myocytes and consequent
ventricular arrhythmias. Heterozygous mutations in PKP2 encoding plakophilin-2
have previously been reported to cause dominant ARVD with reduced penetrance. We
report the first case of recessive ARVD caused by mutations in PKP2. Candidate
gene analysis in a typical proband with this disorder identified a novel
homozygous mutation in PKP2 (c.[2484C>T]+[2484C>T]), which is predicted to be
translationally silent (p.Gly828). Analysis of the proband's mRNA, however, shows
that this mutation causes predominantly cryptic splicing, with a 7-nucleotide
deletion in exon 12. The ensuing frame shift disrupts the last 54 amino acids of
plakophilin-2 and extends the open reading frame by 145 nucleotides (48 amino
acids) into the 3' untranslated region. Haplotype analysis demonstrates the
absence of remote consanguinity. Heterozygous family members produce
approximately 60% of properly spliced PKP2 and do not have manifestations of
ARVD. Further analysis of PKP2 mRNA sequence revealed two additional
alternatively spliced transcripts. The possibility of cryptic or alternative
splicing should be considered with identification of apparently synonymous
nucleotide substitutions in this gene.
PMID- 17041890
TI - Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in
Zellweger spectrum patients.
AB - Mutations in each of the 13 identified human PEX genes are known to cause a
peroxisomal biogenesis defect (PBD). Affected patients can be divided into two
broad clinical spectra: the Zellweger spectrum, which accounts for about 80% of
PBD patients, and the rhizomelia chondrodysplasia punctata (RCDP) spectrum. The
clinical continuum of Zellweger spectrum patients extends from Zellweger syndrome
(ZS) as the prototype and the most severe entity of this group to neonatal
adrenoleukodystrophy (NALD) as an intermediate form and infantile Refsum (IRD)
disease as the mildest variant. Characteristic features of ZS patients are
dysmorphic features, severe neurological impairment, liver dysfunction, and eye
and skeletal abnormalities. Similar but less severe clinical signs are seen in
patients with NALD and IRD. In this study ten clinically and/or biochemically
well-characterized patients with classical ZS were investigated for defects in
all known human PEX genes. We identified two novel mutations in PEX2 (official
symbol, PXMP3), two novel mutations in PEX6, two novel mutations in PEX10, one
novel mutation in PEX12, and one novel mutation in PEX13.
PMID- 17041891
TI - A new genetic isolate with a unique phenotype of syndromic oculocutaneous
albinism: clinical, molecular, and cellular characteristics.
AB - An extended, highly consanguineous Israeli Bedouin family with at least 20
individuals exhibiting a unique phenotype of oculocutaneous albinism (OCA) was
identified. All known OCA genes were excluded in this family. Electron
microscopic analysis of platelets revealed absence of dense bodies, suggesting a
diagnosis of Hermansky-Pudlak syndrome (HPS). HPS is a rare autosomal recessive
disorder of lysosome-related organelle biogenesis, clinically characterized by
OCA and platelet dysfunction, sometimes accompanied by other systemic
pathologies. All human HPS genes (HPS1-8) and five genes corresponding to murine
HPS models were evaluated. Haplotype analysis and homozygosity mapping of the HPS
loci revealed linkage to chromosome 10 in the studied family. Subsequently, a
novel insertion mutation, c.1066-1067insG was identified in HPS6. Most frameshift
mutations generating premature termination codon cause mRNA nonsense mediated
decay (NMD), while intronless genes like HPS6 are usually not monitored by NMD.
Expression analysis revealed no mRNA decay in patient's fibroblasts, hence
truncated protein is most probably produced. Confocal microscopy revealed
abnormal distribution of LAMP-3 (lysosomal associated membrane protein-3) in
fibroblasts from the patients, indicating abnormal trafficking of lysosomal
lineage organelles. So far, a single HPS-6 patient phenotypically similar to HPS
3 and HPS-5 has been identified. The HPS-6 phenotype in the studied family is
unique since it resembles OCA and not HPS. Therefore, our finding broadens the
phenotypic definition of HPS. Two major genetic isolates of HPS-1 and HPS-3
patients were previously diagnosed in Puerto Rico. The extended Bedouin family is
the largest isolate of non-Puerto Rican HPS patients.
PMID- 17041892
TI - The Wnt/beta-catenin pathway: master regulator of liver zonation?
AB - The liver contains two systems for the removal of ammonia - the urea cycle and
the enzyme glutamine synthetase. These systems are expressed in a complementary
fashion in two distinct populations of hepatocytes, referred to as periportal and
perivenous cells. One of the unresolved problems in hepatology has been to
elucidate the molecular mechanisms responsible for induction and maintenance of
the cellular heterogeneity for ammonia detoxification. There is now a potential
molecular explanation for the zonation of the urea cycle and glutamine synthetase
based on the Wnt/beta-catenin pathway.
PMID- 17041894
TI - DiGeorge syndrome and pharyngeal apparatus development.
AB - DiGeorge syndrome is the most frequent microdeletion syndrome in humans, and is
characterized by cardiovascular, thymic and parathyroid, and craniofacial
anomalies. The underlying cause is disturbed formation of the pharyngeal
apparatus, a transient structure present during vertebrate development that gives
rise to endocrine glands, craniofacial tissue, and the cardiac outflow tract. The
pharyngeal apparatus is composed of derivatives of ectoderm, endoderm, mesoderm
and the neural crest. Thus, complex interactions between cell types from
different origins have to be orchestrated in the correct spatiotemporal manner to
establish proper formation of the pharyngeal system. The analysis of engineered
mouse mutants developing a phenotype resembling DiGeorge syndrome has revealed
genes and signalling pathways crucial for this process. Intriguingly, these mouse
models reveal that interference with either of two distinct phases of pharyngeal
apparatus development can contribute to the aetiology of DiGeorge syndrome.
PMID- 17041893
TI - Measurement of phosphorus content in normal and osteomalacic rabbit bone by solid
state 3D radial imaging.
AB - In osteomalacia decreased mineralization reduces the stiffness and static
strength of bone. We hypothesized that hypomineralization in osteomalacic bone
could be quantified by solid-state (31)P magnetic resonance imaging (SS-MRI).
Hypomineralization was measured with a 3D radial imaging technique at 162 MHz
(9.4T) in rabbit cortical bone of hypophosphatemic (HY) and normophosphatemic
(NO) animals. The results were compared with those obtained by quantitative micro
CT (micro-CT) and (31)P solution NMR. 3D images of 277 microm isotropic voxel
size were obtained in 1.7 hr with SNR approximately 9. Mineral content was lower
in the HY relative to the NO group (SS-MRI: 9.48 +/- 0.4 vs. 11.15 +/- 0.31
phosphorus wet wt %, P < 0.0001; micro-CT: 1114.6 +/- 28.3 vs. 1175.7 +/- 23.5 mg
mineral/cm(3); P = 0.003). T(1) was shorter in the HY group (47.2 +/- 3.5 vs.
54.1 +/- 2.7 s, P = 0.004), which suggests that relaxation occurs via a dipole
dipole (DD) mechanism involving exchangeable water protons, which are more
prevalent in bone from osteomalacic animals.
PMID- 17041895
TI - Genome-wide prediction of genetic interactions in a metazoan.
AB - Genetic interactions provide information about genes and processes with
overlapping functions in biological systems. For Saccharomyces cerevisiae,
computational integration of multiple types of functional genomic data is used to
generate genome-wide predictions of genetic interactions. However, this
methodology cannot be applied to the vastly more complex genome of metazoans, and
only recently has the first metazoan genome-wide prediction of genetic
interactions been reported. The prediction for Caenorhabditis elegans was
generated by computationally integrating functional genomic data from S.
cerevisiae, C. elegans and Drosophila melanogaster. This achievement is an
important step toward system-level understanding of biological systems and human
diseases.
PMID- 17041896
TI - Identification of novel mutations in the human ornithine transcarbamylase (OTC)
gene of Korean patients with OTC deficiency and transient expression of the
mutant proteins in vitro.
AB - The urea cycle plays key roles to prevent the accumulation of toxic nitrogenous
compound and synthesize arginine de novo. Ornithine transcarbamylase (OTC)
deficiency is the most common inborn error of urea cycle, which is inherited in
an X-linked manner. This study was undertaken to characterize molecular defects
in Korean patients with OTC deficiency. With direct sequence analysis of OTC gene
of 26 unrelated Korean patients with OTC deficiency, 23 different mutations were
identified. Among these mutations, eleven were novel mutations. The novel
mutations were p.Leu9X, p.Arg26Pro, p.Gly100Arg, p.Met205Thr, p.Lys221Asn,
p.Asp249Gly, p.Phe281Ser, p.Val323Met, c.571delC, c.853delC, and c.796-805del.
All the novel mutations in this study were tested in 100 normal alleles. In vitro
expression study of some of novel missense mutations elucidated the correlation
of genotype and phenotype of the OTC deficiency.
PMID- 17041897
TI - Deficient membrane integration of the novel p.N14D-GJB2 mutant associated with
non-syndromic hearing impairment.
AB - Mutations in GJB2, the gene encoding for the Gap Junction protein Connexin 26
(Cx26), have been established as the major cause of hereditary, non-syndromic
hearing impairment (HI). We report here the identification of a novel point
mutation in GJB2, c.40A>G [p.N14D], detected in compound heterozygosity with the
c.35delG mutation in two brothers with moderate non-syndromic sensorineural HI.
The mother who carried one wildtype and a p.N14D allele displayed normal hearing.
The mutation leads to substitution of the neutral amino acid asparagine (N) by
the negatively charged aspartic acid (D) at amino acid number 14, a position that
is conserved among Cx26 of different organisms and among many other connexin
isoforms. To investigate the impact of this mutation on protein function, Cx26
activity was measured by depolarization activated hemichannel conductance in non
coupled Xenopus laevis oocytes. Oocytes injected with the p.N14D mutant cRNA
showed strongly reduced currents compared to wildtype. Coinjection of wildtype
and mutant cRNA at equimolar levels restored the conductive properties supporting
the recessive character of this mutation. Total Cx26 protein expression and cell
surface abundance examined by western blotting and by quantitative immunoassays
revealed that the hemichannel was properly synthesized but not integrated into
the plasma membrane. In this study we have shown that the GJB2 mutation p.N14D is
associated with recessively inherited HI and exhibits a defective phenotype due
to diminished expression at the cell surface.
PMID- 17041898
TI - Reactive oxygen species as signals that modulate plant stress responses and
programmed cell death.
AB - Reactive oxygen species (ROS) are known as toxic metabolic products in plants and
other aerobic organisms. An elaborate and highly redundant plant ROS network,
composed of antioxidant enzymes, antioxidants and ROS-producing enzymes, is
responsible for maintaining ROS levels under tight control. This allows ROS to
serve as signaling molecules that coordinate an astonishing range of diverse
plant processes. The specificity of the biological response to ROS depends on the
chemical identity of ROS, intensity of the signal, sites of production, plant
developmental stage, previous stresses encountered and interactions with other
signaling molecules such as nitric oxide, lipid messengers and plant hormones.
Although many components of the ROS signaling network have recently been
identified, the challenge remains to understand how ROS-derived signals are
integrated to eventually regulate such biological processes as plant growth,
development, stress adaptation and programmed cell death.
PMID- 17041899
TI - Red cell glucose phosphate isomerase (GPI): a molecular study of three novel
mutations associated with hereditary nonspherocytic hemolytic anemia.
AB - Molecular characteristics of red blood cell (RBC) glucose phosphate isomerase
(GPI) deficiency are described in two Spanish patients with chronic
nonspherocytic hemolytic anemia. One patient, with residual GPI activity in RBCs
of around 7% (GPI-Catalonia), is homozygous for the missense mutation c.1648A>G
(p.Lys550Glu) in exon 18. The other patient, with residual activity in RBCs of
around 20% (GPI-Barcelona), was found to be a compound heterozygote for two
different missense mutations: c.341A>T (p.Asp113Val) in exon 4 and c.663T>G
(p.Asn220Lys) in exon 7. Molecular modeling using the human crystal structure of
GPI as a model was performed to determine how these mutations could affect enzyme
structure and function.
PMID- 17041900
TI - On the dynamic nature of positional information.
AB - Morphogenetic fields are among the most fundamental concepts of embryology.
However, they are also among the most ill-defined, since they consist of dynamic
regulatory processes whose exact nature remains elusive. In order to achieve a
more rigorous definition of a developmental field, Lewis Wolpert introduced the
concept of positional information illustrated by his French Flag model. Here we
argue that Wolpert's positional information - a static coordinate system defining
a field - lacks essential properties of the original field concept. We show how
data-driven mathematical modeling approaches now enable us to study regulatory
processes in a way that is qualitatively different from our previous level of
understanding. As an example, we review our recent analysis of segmentation gene
expression in the blastoderm embryo of the fruit fly Drosophila melanogaster.
Based on this analysis, we propose a revised French Flag, which incorporates the
dynamic, feedback-driven nature of pattern formation in the Drosophila
blastoderm.
PMID- 17041901
TI - On the origins of morphological disparity and its diverse developmental bases.
AB - It has been repeatedly claimed that morphological novelties are an unresolved
problem in evolutionary theory. Several definitions of novelty exist but most
emphasize that novelties imply qualitative changes on the phenotype and not the
quantitative gradual changes favored in the neo-Darwinian approach to
evolutionary theory. This article discusses how the concept of novelty is used to
describe aspects of morphological evolution that are not satisfactorily explained
under the modern synthesis. In this article, it is suggested that there is a
repertoire of morphological changes rather than two discrete qualitatively
different types of morphological change. How these different types of
morphological changes can be understood from the diversity of developmental
mechanisms existing in animal development is explored. Specifically, it is
proposed that animal morphology and its variation can be understood from the
spatial patterns produced by a set of basic developmental mechanisms and their
combination. Some specific examples of these kinds of morphologic changes are
explained.
PMID- 17041902
TI - Meiosis and sex: potent weapons in the competition between early eukaryotes and
prokaryotes.
AB - The earliest eukaryote species almost certainly evolved in an environment
dominated by numerous prokaryotic species. If the first eukaryotic cells were
larger and grew more slowly than their prokaryotic neighbours, they might well
have been at a competitive disadvantage. It is proposed here that the early
evolution of meiosis, with its capacity for generating new favourable gene
combinations, might have served to offset any such competitive disadvantages.
Meiosis and sex could have arisen in an asexually reproducing species and formed
a clonal population.
PMID- 17041903
TI - Detection of ultrarare somatic mutation in the human TP53 gene by bidirectional
pyrophosphorolysis-activated polymerization allele-specific amplification.
AB - The detection of ultra-rare mutation in the presence of excess amounts of normal
genomic DNA is highly advantageous in a number of circumstances, including: 1)
identification of minimal residual disease for improved cancer chemotherapy; 2)
measurement of mutation load to assess environmental mutagen exposure or
endogenous DNA repair; and 3) prenatal diagnosis of paternally-derived mutations
within fetal cells in the maternal circulation. Bidirectional pyrophosphorolysis
activated polymerization allele-specific amplification (Bi-PAP-A) utilizes two
opposing 3'-terminal blocked oligonucleotides (P(*)s) with 1 nucleotide overlap
at their 3' termini. The selectivity of Bi-PAP-A derives from the serial coupling
of pyrophosphorolysis and DNA polymerization. A total of 13 Bi-PAP-A assays were
developed and validated for the human p53 gene (TP53). The sensitivity and
specificity of each assay were determined with mutated and wild-type DNA
templates, respectively. Bi-PAP-A has a sensitivity of one molecule for most
assays and a selectivity (sensitivity:specificity) greater than 1:10(7)-1:10(9)
for four of all six mutation types. Four assays with high selectivity were used
to detect rare somatic mutations in blood white cells. The silent g.13147C>G
(p.R156) mutation was present at an estimated frequency of 1.1 x 10(-7). The
g.14523A>T (p.E285V), g.14487G>C (p.R273P), and g.14060G>C (p.G245R) mutations
were undetectable with frequencies less than 2.0 x 10(-8). We conclude that Bi
PAP-A is a general and rapid method for detecting ultra-rare mutations.
PMID- 17041904
TI - Autophagy in neuronal cell loss: a road to death.
AB - The regulation of ageing has been extensively studied in divergent animal model
systems including worms, flies and mice. However, little is known about the
cellular pathways that mediate the death of these organisms. Analysing major
cellular changes in the ageing nematode Caenorhabditis elegans has revealed a
gradual, progressive deterioration of different tissues except for the nervous
system, which remarkably preserves its integrity even in advanced old age. In
addition, genetic data have shown that, in C. elegans and in the fruit fly
Drosophila melanogaster, lifespan is controlled by signals derived from neurons
and acting throughout adulthood. Organismal death thus seems to be a consequence
of the decline of specific neurons. Accumulating evidence demonstrates that late
onset of neuronal cell loss generally occurs via autophagy, a process in which
eukaryotic cells self-digest parts of their contents during development or to
survive starvation. Here we suggest that overactivation of autophagy in the cells
of the nervous system is the eventual cause of "physiological" death.
PMID- 17041905
TI - mRNPs take shape by CLIPPING and PAIRING.
AB - The interaction of RNA-binding proteins (RBPs) with RNA is a crucial aspect of
normal cellular metabolism. Yet, the diverse number of RBPs and RNA motifs to
which they bind, the wide range of interaction strengths and the fact that RBPs
associate in dynamic complexes have made it challenging to determine whether a
particular RNA-binding protein binds a particular RNA. Recent work by three
different laboratories has led to the development of new tools to query such
interactions in the more physiological environs of cultured cells. The use of
these methods has led to insights into (1) the networks of RNAs regulated by a
particular protein, (2) the identification of new protein partners within
messenger ribonucleoprotein particles and (3) the flux of RNA-binding proteins on
an mRNA throughout its lifecycle. Here, I examine these new methods and discuss
their relative strengths and current limitations.
PMID- 17041906
TI - Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point
mutations and molecular basis for BMD with nonsense and frameshift mutations in
the DMD gene.
AB - Straightforward detectable Duchenne muscular dystrophy (DMD) gene rearrangements,
such as deletions or duplications involving an entire exon or more, are involved
in about 70% of dystrophinopathies. In the remaining 30% a variety of point
mutations or "small" mutations are suspected. Due to their diversity and to the
large size and complexity of the DMD gene, these point mutations are difficult to
detect. To overcome this diagnostic issue, we developed and optimized a routine
muscle biopsy-based diagnostic strategy. The mutation detection rate is almost as
high as 100% and mutations were identified in all patients for whom the diagnosis
of DMD and Becker muscular dystrophy (BMD) was clinically suspected and further
supported by the detection on Western blot of quantitative and/or qualitative
dystrophin protein abnormalities. Here we report a total of 124 small mutations
including 11 nonsense and frameshift mutations detected in BMD patients. In
addition to a comprehensive assessment of muscular phenotypes that takes into
account consequences of mutations on the expression of the dystrophin mRNA and
protein, we provide and discuss genomic, mRNA, and protein data that pinpoint
molecular mechanisms underlying BMD phenotypes associated with nonsense and
frameshift mutations.
PMID- 17041907
TI - Fourth international symposium on the biology of vertebrate sex determination.
PMID- 17041908
TI - Recruitment pharmacophore for interleukin 5 receptor alpha antagonism.
AB - Interleukin-5 receptor alpha is a therapeutic target for hypereosinophilic
diseases including allergic inflammations and asthma. The cyclic peptide AF17121
(Ac-VDE[CWRIIASHTWFC]AEE-CONH(2)) has been identified as a submicromolar
inhibitor of interleukin 5 (IL5)-interleukin 5 receptor alpha (IL5Ralpha)
interaction from a random peptide screen. However, this inhibitor has limitations
as a drug lead because of its relatively large size. We used chemical synthesis
of peptides with natural and non-natural amino acids along with kinetic binding
and cell proliferation competition assays to expand definition of structural
elements in the peptide that are important for receptor antagonism and to
elucidate the underlying pharmacophore. We found that the specific steric array
of hydrogen bonding groups in the Arg 6 guanido side chain is critical for
receptor inhibition. We also investigated noncharged structural elements in
AF17121. Screening a set of five hydrophobic residues showed that peptide
function is strongly sensitive to variations in several of these residues, most
prominently Ile 7 and Trp 13. We postulate that presentation of charged, hydrogen
bonding and hydrophobic structural elements within the disulfide-constrained
peptide drives IL5Ralpha recruitment by AF17121. We hypothesize from these
results and previous receptor mutagenesis studies that Arg 6 recruitment of
IL5Ralpha occurs through hydrogen bonding as well as charge-charge interactions
with Asp 55 in site one of domain 1 of IL5Ralpha, and that this interaction is
complemented by additional charged and hydrophobic interactions around the Asp 55
locus. Scaffolding a limited set of structural elements in the inhibitor
pharmacophore may be useful for small molecule antagonist design inspired by the
peptide.
PMID- 17041909
TI - Human biology: an ever-expanding subject.
PMID- 17041910
TI - Multiexon skipping leading to an artificial DMD protein lacking amino acids from
exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular
dystrophy.
AB - Approximately two-thirds of Duchenne muscular dystrophy (DMD) patients show
intragenic deletions ranging from one to several exons of the DMD gene and
leading to a premature stop codon. Other deletions that maintain the
translational reading frame of the gene result in the milder Becker muscular
dystrophy (BMD) form of the disease. Thus the opportunity to transform a DMD
phenotype into a BMD phenotype appeared as a new treatment strategy with the
development of antisense oligonucleotides technology, which is able to induce an
exon skipping at the pre-mRNA level in order to restore an open reading frame.
Because the DMD gene contains 79 exons, thousands of potential transcripts could
be produced by exon skipping and should be investigated. The conventional
approach considers skipping of a single exon. Here we report the comparison of
single- and multiple-exon skipping strategies based on bioinformatic analysis. By
using the Universal Mutation Database (UMD)-DMD, we predict that an optimal
multiexon skipping leading to the del45-55 artificial dystrophin (c.6439_8217del)
could transform the DMD phenotype into the asymptomatic or mild BMD phenotype.
This multiple-exon skipping could theoretically rescue up to 63% of DMD patients
with a deletion, while the optimal monoskipping of exon 51 would rescue only 16%
of patients.
PMID- 17041911
TI - Advanced three-dimensional tailored RF pulse for signal recovery in T2*-weighted
functional magnetic resonance imaging.
AB - T(2) (*)-weighted functional MR images are plagued by signal loss artifacts
caused by susceptibility-induced through-plane dephasing. We present major
advances to the original three-dimensional tailored RF (3DTRF) pulse method that
pre-compensates the dephasing using three-dimensional selective excitation. The
proposed 3DTRF pulses are designed iteratively with off-resonance incorporation
and with a novel echo-volumar trajectory that frequency-encodes in z and phase
encodes in x,y. We also propose a computational scheme to accelerate the pulse
design process. We demonstrate effective signal recovery in a 5-mm slice in both
phantom and inferior brain, using 3DTRF pulses that are only 15.4 ms long.
Compared to the original method, the new approach leads to significantly reduced
pulse length and enhancement in slice selectivity. 3D images of the slice volume
confirm fidelity of the excited phase pattern and slice profile.
PMID- 17041912
TI - The effect of zoledronic acid incorporated in a poly(D,L-lactide) implant coating
on osteoblasts in vitro.
AB - Bisphosphonates such as zoledronic acid (ZOL) are used in diseases associated
with osteoclast-mediated bone loss. However, their antiresorptive activity is
partly due to their effect on osteoblasts. Local application might increase the
therapeutical fence and their local efficiency and reduce systemic side effects.
Aim of the study was to investigate the effect of ZOL on human osteoblasts like
cells in vitro with special focus on the synthesis of factors mediating
osteoclast differentiation (RANKL, OPG). ZOL was incorporated in an implant
coating based on poly(D,L-lactide) (PDLLA) in different concentrations (10-150
microM). Control groups were treated with uncoated implants, PDLLA-coated
implants, and ZOL pure substance in corresponding concentrations. After an
experimental period of 144 h, primary human osteoblasts were stained with alamar
blue and cell viability was measured. Procollagen I synthesis, osteoprotegerin
(OPG) secretion, and soluble receptor activator of nuclear factor-kappaB ligand
(sRANKL) were analyzed. Results showed that cell viability was not affected when
treated with doses equivalent up to 100 microM ZOL-coated implants (ZOL-CI).
Procollagen I synthesis was highest when treated with 50 microM ZOL-CI. OPG
increased significantly in the 10 microM ZOL-CI group, whereas sRANKL decreased
significantly with different concentrations of ZOL-CI. Higher concentrations or
exposure to the pure substance showed a decrease in cell viability, collagen I,
OPG, and sRANKL synthesis. In conclusion, exposure to specific concentrations of
ZOL-CI showed a beneficial effect on osteoblast differentiation and protein
synthesis without influencing their proliferation. Changes in sRANKL and OPG
production may contribute to the inhibition of osteoclastic bone resorption. This
local antiresorptive effect might be clinically useful in osseous implant
integration and fracture healing.
PMID- 17041913
TI - Effects of collagen fiber orientation on the response of biologically derived
soft tissue biomaterials to cyclic loading.
AB - In the present study, the effects of initial collagen fiber orientation on the
medium-term (up to 50 x 10(6) cycles) fatigue response of heart valve soft tissue
biomaterials was investigated. Glutaraldehyde treated bovine pericardium (GLBP),
preselected for uniform structure and collagen fiber orientation, was used as the
representative heart valve biomaterial. Using specialized instrumentation, GLBP
specimens were subjected to cyclic tensile loading to maximum stress levels of
500 +/- 50 kPa at a frequency of 22 Hz. Two sample groups were examined, one with
the preferred collagen fiber direction parallel (PD) and perpendicular (XD) to
the direction of applied strain. The primary findings indicated that GLBP fatigue
response was highly sensitive to the direction of loading with respect to fiber
orientation. Specifically, when loading perpendicular to the preferred collagen
fiber orientation, fiber reorientation is the dominant mechanism. In contrast,
when loaded parallel to the preferred fiber direction a reduction in both
collagen fiber crimp and fiber reorientation occurred. Moreover, alterations in
the degree and direction of mechanical anisotropy can be inducted by cyclic
loading when specimens are loaded perpendicular to the preferred fiber direction.
Fourier Transform Infrared Spectroscopy (FT-IR) results indicate that molecular
level damage to collagen occurs in both groups after only 20 x 10(6) cycles.
Taken as a whole, the results of this study suggest that initial collagen
orientation plays a critical role in bioprosthetic heart valve biomaterial
fatigue response.
PMID- 17041914
TI - Rumination in posttraumatic stress disorder.
AB - Recent studies have shown that rumination is a powerful predictor of persistent
posttraumatic stress disorder (PTSD). However, to date, the mechanisms by which
rumination maintains PTSD symptoms are little understood. Two studies of assault
survivors, a cross-sectional (N = 81) and a 6-month prospective longitudinal
study (N = 73), examined several facets of ruminative thinking to establish which
aspects of rumination provide the link to PTSD. The current investigation showed
that rumination is not only used as a strategy to cope with intrusive memories
but it also triggers such memories. Certain characteristics of rumination, such
as compulsion to continue ruminating, occurrence of unproductive thoughts, and
"why" and "what if" type questions, as well as negative emotions before and after
rumination, were significantly associated with PTSD, concurrently and
prospectively. These characteristics explained significantly more variance in
PTSD severity than the mere presence of rumination, thereby indicating that not
all ways of ruminative thinking are equally maladaptive.
PMID- 17041915
TI - Association of cigarette smoking and depressive symptoms in a forensic
population.
AB - The link between mental health issues and smoking has been an important area of
investigation. However, little is known about this association in a general
adult, male forensic population. The aim of this study was to identify
demographic and clinical (depression and anxiety) variables that predict smoking
in a forensic population. A large cohort of 353 inmates in a high-security prison
underwent a psychiatric interview, including administration of the Montgomery
Asberg Rating Scale for Depression (MADRS) and Hamilton's Rating Scale for
Anxiety (HAM-A). Multiple regression analysis suggested that younger age and
higher depression scores might predict the amount of daily smoking in this
population. In contrast, anxiety symptoms were not an independent predictor for
smoking in our study. These findings support the need for additional research to
focus on those factors associated with smoking in forensic populations.
Psychiatric screening for younger male individuals in forensic settings and
targeted cognitive-behavioral interventions to treat depressed smokers may
ameliorate the smoking abstinence rate in prisons.
PMID- 17041916
TI - Sieving functional morphology of the gill raker feeding apparatus of atlantic
menhaden.
AB - Menhaden occupy an important position in estuarine food webs, thus the rate
processes associated with their feeding are critical to the ecosystem management
of fishery and ecological resources. Atlantic menhaden feed on a wide range of
plankton, the size and food quality of which change ontogenetically. We analyzed
the functional morphology of the menhaden feeding apparatus in a size series of
menhaden representative of juveniles and the adult migratory stock. The physical
dimensions of gill arches and rakers increased isometrically with fish length;
however, branchiospinule spacing, the dimension that forms the sieve apertures of
the branchial basket, scaled allometrically with fish length. Juvenile menhaden
from North Carolina have branchiospinule spacings that averaged 12 microm, with
three arch subsections of average spacing < 10 microm. Spacings did not increase
with juvenile growth until the first allometric inflection point at approximately
100 mm fork length (FL). Spacing data for juveniles from other locations suggests
spacing increases with latitude. Spacings increase with fish length in adults
until a second inflection at 200 mm FL, after which spacing averages 37 microm.
These data suggest menhaden juveniles filter smaller plankton with higher
filtration efficiency than previously considered and that regional recruitment
may affect adult distribution through foraging preferences.
PMID- 17041917
TI - Uterine motility in the reptile Anolis carolinensis: interactive effects of
tension, prostaglandins, calcium, and vasotocin.
AB - Uteri of Anolis carolinensis exhibited spontaneous rhythmic contractions in
vitro. Addition of arginine vasotocin (AVT) caused an immediate, strong, tonic
contraction followed by rhythmic contractions with the same frequency as
spontaneous contractions but of a greater amplitude. At low tension (1.5 g) the
AVT-induced tonic contraction was blocked by low dose of indomethacin, suggesting
that it is influenced by calcium rather than prostaglandins (PGs). An increase in
tension (from 1.5 to 15 g) reduced the duration of the AVT-induced tonic
contraction; this stretch-induced decrease was also blocked by indomethacin.
Stretch also decreased the duration of the rhythmic contractions, but this
stretch effect was not inhibited by indomethacin. The rest interval between
rhythmic contractions was decreased by PGF2alpha and PGE2, and indomethacin or
stretch blocked these PG effects. Indomethacin, AVT, or stretch alone did not
affect PGF2alpha secretion from AVT-treated uteri. Stretch also reduced PGF2alpha
secretion from AVT-treated uteri, an effect inhibited by indomethacin.
PMID- 17041918
TI - Regulation of immunocompetence by different androgen metabolites in a blenny with
alternative reproductive tactics.
AB - In Parablennius parvicornis, small reproductive males with relatively low
expression of secondary sexual characters (M- morphotype) parasite on the
parental investment of the larger nest-holder males which have fully developed
secondary sexual characters (M+ morphotype). In comparison with M+ males, M-
males have relatively low levels of androgens while having high blood cell
percentages of lymphocytes and antigen responsiveness. Here we test the
hypothesis that androgens are a causal factor for these differences in
immunocompetence between morphotypes. After drawing an initial blood sample,
males received a silastic implant containing either oil only (C), or oil with
testosterone (T) or 11-ketotestosterone (KT). Males were re-caught 2 weeks later
for drawing of the final blood sample. KT but not T induced the development of
secondary sexual characters in M- males. M- males treated with KT showed lower
swimming activity than the males treated with T or C implants, suggesting that KT
also mediates behavioral changes in M- males. As expected, blood cell percentages
of lymphocytes, but not of granulocytes, were higher in M- males than in M+
males. Overall, lymphocyte percentages increased in the C group which might have
been a response to the surgery/treatment. In concordance with the hypothesis,
lymphocyte percentages were suppressed in males treated with T in comparison with
controls. However, no significant change was found in KT-treated males. This
suggests that androgens modulate central, morphological and immunological traits
by partly independent androgen mechanisms in P. parvicornis.
PMID- 17041919
TI - Structure-activity relationship studies of a series of peptidomimetic ligands for
alpha(4) beta(1) integrin on Jurkat T-leukemia cells.
AB - alpha(4)beta(1) integrin is a therapeutic target for inflammation, autoimmune
diseases, and lymphoid cancers. A series of peptidomimetic ligands based on the
Nle-D-I motif have been synthesized and their binding affinities (IC(50)) to
activated alpha(4)beta(1) integrin on Jurkat T-leukemia cells have been
determined using a cell adhesion assay. One of the 51 ligands, 18, has been
determined to have an IC(50) of 0.6 nM and has a more than twofold increase of
binding affinity than the initial lead compound 1. Extensive SAR studies provide
important information for further ligand optimization, which has served as a
foundation for studies that ultimately led to identification of a potent ligand
with an IC(50) of 2 pM.
PMID- 17041920
TI - Pineal germinoma presenting as anorexia nervosa: Case report and review of the
literature.
AB - OBJECTIVE: Tumors of the hypothalamic-pineal region may present with a wide
variety of symptoms, including disturbed eating. We present a case where such a
tumor was misdiagnosed as anorexia nervosa. METHOD: We describe a case of pineal
germinoma invading the hypothalamus, which was initially diagnosed as anorexia
nervosa. RESULTS: Clinical features included weight loss, vomiting, pyrexia,
hypernatraemia, and visual disturbance and the typical psychopathology of
anorexia nervosa was absent. CONCLUSION: Organic disorder should always be
considered before making a diagnosis of anorexia nervosa, particularly if the
presentation is atypical.
PMID- 17041921
TI - Korean Anxiety Sensitivity Index-Revised: its factor structure, reliability, and
validity in clinical and nonclinical samples.
AB - The factor structure and convergent and discriminant validity of the Anxiety
Sensitivity Index-Revised (ASI-R) were examined in a community sample, a student
sample, and patients with panic disorder in Korea. Results from a confirmatory
factor analysis (CFA) comparing our data to factor solutions commonly reported as
representative of European American populations indicated a poor fit. A
subsequent exploratory factor analysis (EFA) indicated that a four-factor
solution provided the best fit. Correlations between the ASI-R and anxiety
measures were moderately high, providing evidence of convergent validity.
Implications for assessment with Koreans are discussed.
PMID- 17041922
TI - A prospective study of escitalopram in the treatment of major depressive episodes
in the presence or absence of anxiety.
AB - This open, multicenter, prospective study in France assessed the efficacy and
tolerability of escitalopram in patients with depression, with or without
comorbid anxiety. Escitalopram was administered over a 12-week treatment period
to 790 depressed patients, including 482 patients with at least one concomitant
anxiety disorder. The study was completed by 649 patients. At baseline, the mean
Montgomery-Asberg Depression Rating Scale (MADRS) total score was 31.5 and
decreased to 12.4 at end point (last observation carried forward [LOCF]). The
MADRS score decreased by 20.5 points in patients with no anxiety disorder and by
18.3 points in patients with at least one concomitant anxiety disorder. The mean
Hamilton Anxiety Rating Scale (HAM-A) total score at baseline was 25.6, which
decreased to 10.8 at end point (LOCF). The HAM-A score decreased by 13.8 points
in patients with no anxiety disorder and by 15.5 points in patients with at least
one anxiety disorder. Adverse events were reported by 246 patients (31%). The
most frequent adverse events were nausea in 65 patients (8%) and headache in 38
patients (5%); 61 patients (8%) discontinued treatment due to adverse events.
Escitalopram was well tolerated and efficacious in reducing symptoms of
depression in patients with or without comorbid anxiety over a 12-week treatment
period.
PMID- 17041923
TI - A novel G106D alteration of the SDHD gene in a pedigree with familial
paraganglioma.
AB - Head and neck paragangliomas are tumors derived from parasympathetic paraganglia.
Familial cases account for 10% or more of these tumors, and mutations of the
genes encoding subunits for the mitochondrial respiratory chain complex II, SDHD,
SDHB, and SDHC, have been reported. We analyzed mutations in the all four SDH
genes, SDHA through SDHD, in a Japanese family with cervical paraganglioma that
include a father with bilateral tumors and his daughter with a malignant left
carotid body tumor with nodal metastasis. This pedigree harbored a germline G106D
alteration in exon 4 of the SDHD gene that has not previously been reported to
date. The tumors of the father expressed biallelic SDHD, but the SDHD expression
was highly suppressed by an unknown mechanism(s) in tumors of his daughter, and
the wild-type allele was predominantly suppressed in the metastatic node. These
results suggest that the missense dysfunction of SDHD prepares neoplastic
condition and that expressional silencing, particularly of the wild-type allele,
plays an important role in the malignant transformation of the paragangliomas.
Our results may lead to a better understanding of this disease and to the
development of methods for prevention of this disease.
PMID- 17041924
TI - Friction of total hip replacements with different bearings and loading
conditions.
AB - Metal-on-ultra-high molecular weight polyethylene (UHMWPE) total hip replacements
have been the most popular and clinically successful implants to date. However,
it is well documented that the wear debris from these prostheses contributes to
osteolysis and ultimate failure of the prosthesis, hence alternative materials
have been sought. A range of 28 mm diameter bearings were investigated using a
hip friction simulator, including conventional material combinations such as
metal-on-UHWMPE, ceramic-on-ceramic (CoC), and metal-on-metal (MoM), as well as
novel ceramic-on-metal (CoM) pairings. Studies were performed under different
swing-phase load and lubricant conditions. The friction factors were lowest in
the ceramic bearings, with the CoC bearing having the lowest friction factor in
all conditions. CoM bearings also had low friction factors compared with MoM, and
the trends were similar to CoC bearings for all test conditions. Increasing swing
phase load was shown to cause an increase in friction factor in all tests.
Increased serum concentration resulted in increased friction factor in all
material combinations, except MoM, where increased serum concentration produced a
significant reduction in friction factor.
PMID- 17041925
TI - In vivo performance of antibiotic embedded electrospun PCL membranes for
prevention of abdominal adhesions.
AB - The aim of this study was to prepare nonwoven materials from poly(epsilon
caprolactone) (PCL) and their antibiotic containing forms by electrospinning, so
as to prevent postsurgery induced abdominal adhesions in rats. epsilon
Caprolactone was first polymerized by ring-opening polymerization, and then it
was processed into matrices composed of nanofibers by electrospinning. A model
antibiotic (Biteral) was embedded within a group of PCL membranes. In the rat
model, defects on the abdominal walls in the peritoneum were made to induce
adhesion. The plain or antibiotic embedded PCL membranes were implanted on the
right side of the abdominal wall. No membrane implantation was made on the left
side of the abdominal wall that served as control. Macroscopical and histological
evaluations showed that using these barriers reduces the extent, type, and
tenacity of adhesion. The antibiotic embedded membranes significantly eliminated
postsurgery abdominal adhesions, and also improved healing.
PMID- 17041926
TI - Evaluation of an accelerated aging medium for acrylic bone cement based on
analysis of nanoindentation measurements on laboratory-prepared and retrieved
specimens.
AB - The thrust of the study was a critical evaluation of the efficacy of a medium
(30% v/v H(2)O(2), at 60 degrees C) that has been suggested in a literature
report as being suitable for simulating the oxidative aging process, seen in
vivo, in the acrylic bone cement mantles of total hip and knee joint
replacements. For this purpose, quasi-static and dynamic nanoindentation
measurements were used to obtain material properties--elastic modulus, E;
hardness, H; and the variation of the storage and loss moduli with the frequency
of the applied indenting force--of PalacosR acrylic bone cement specimens after
various periods of immersion (7, 14, 21, and 28 days) in the aging solution, and
of specimens prepared from cement mantles retrieved from cemented total hip joint
replacements after various times in vivo (0.92-21 years). Also, best-fit
relationships were obtained between E and time in the H(2)O(2) solution (t), H
and t, E and in vivo time (T), and H and T. This body of results points to the
possibility that the aging solution is effective, although the evidence is not
conclusive.
PMID- 17041927
TI - Neurotrophin-eluting hydrogel coatings for neural stimulating electrodes.
AB - Improved sensory and motor prostheses for the central nervous system will require
large numbers of electrodes with low electrical thresholds for neural excitation.
With the eventual goal of reducing stimulation thresholds, we have investigated
the use of biodegradable, neurotrophin-eluting hydrogels (i.e., poly(ethylene
glycol)-poly(lactic acid), PEGPLA) as a means of attracting neurites to the
surface of stimulating electrodes. PEGPLA hydrogels with release rates ranging
from 1.5 to 3 weeks were synthesized. These hydrogels were applied to
multielectrode arrays with sputtered iridium oxide charge-injection sites. The
coatings had little impact on the iridium oxide electrochemical properties,
including charge storage capacity, impedance, and voltage transients during
current pulsing. Additionally, we quantitatively examined the ability of
neurotrophin-eluting, PEGPLA hydrogels to promote neurite extension in vitro
using a PC12 cell culture model. Hydrogels released neurotrophin (nerve growth
factor, NGF) for at least 1 week, with neurite extension near that of an NGF
positive control and much higher than extension seen from sham, bovine serum
albumin-releasing boluses, and a negative control. These results show that
neurotrophin-eluting hydrogels can be applied to multielectrode arrays, and
suggest a method to improve neuron-electrode proximity, which could result in
lowered electrical stimulation thresholds. Reduced thresholds support the
creation of smaller electrode structures and high density electrode prostheses,
greatly enhancing prosthesis control and function.
PMID- 17041928
TI - Protective effects of antioxidants on micronuclei induced by camphorquinone/N,N
dimethyl-p-toluidine employing in vitro mammalian test system.
AB - Camphorquinone (CQ) is widely used as an initiator in modern visible-light (VL)
cured resin systems. CQ is also characterized as a potential allergenic compound.
To date, there is growing concern that CQ may produce genetic damage by inducing
mutation. In this study, CQ in the presence of reducing agent N,N-dimethyl-p
toluidine (DMT) with or without VL irradiation was analyzed for the induction of
chromosomal aberrations indicated by micronuclei (MN) induced in CHO cells. Our
data demonstrated that an increase in the numbers of MN was observed with CQ/DMT
with or without VL irradiation (p < 0.05). Significant prolongation of cell
cycles was observed by the treatment with CQ/DMT with or without VL irradiation
(p < 0.05). In addition, VL irradiated CQ/DMT was found to exhibit significantly
genotoxic and cytotoxic effects as compared with CQ/DMT alone (p < 0.05).
Furthermore, to determine whether oxidative stress could modulate the MN induced
by CQ/DMT with or without VL irradiation in CHO cells, cells were pre-treated
with various antioxidants 10 mM N-acetyl-L-cysteine (NAC), 2 mM ascorbic acid,
and 2 mM alpha-tocopherol. The pre-treatment with antioxidants could antagonize
not only the increased MN cells but also the prolonged cell cycle induced by
CQ/DMT with or without VL irradiation in CHO cells (p < 0.05). Our findings
provide the evidences for the induction of MN by CQ/DMT employing mammalian test
system, indicating clastogenic activity of CQ/DMT with or without VL irradiation
in vitro. In addition, VL irradiated CQ/DMT exhibits higher genotoxic and
cytotoxic effects than CQ/DMT alone. Moreover, NAC, ascorbic acid, and alpha
tocopherol act as the antagonists against the genotoxicity and cytotoxicity of
CQ/DMT with or without VL irradiation.
PMID- 17041929
TI - Psychosocial outcomes of anxious first graders: a seven-year follow-up.
AB - This study examined the concurrent and long-term psychosocial outcomes associated
with anxiety symptoms among a community sample of predominately low-income
African Americans (N=149; 72 females). We classified first graders as high or low
anxious using child, parent, and teacher reports. Academic, social, and
psychological outcomes were assessed in the first and eighth grades. Logistic
regressions with concurrent data revealed that highly anxious children were
significantly more likely to score lower on measures of academic achievement and
peer acceptance, but higher on measures of depression and aggression compared to
their low-anxious peers. Longitudinal analyses revealed that high-anxious first
graders, compared to their low-anxious peers, scored significantly lower on
measures of academic achievement, aggression, and peer acceptance; and higher on
measures of anxiety and depression in the eighth grade. Importantly, outcomes
varied depending on informant. Findings suggest that, similar to European
American youth, early-onset anxious symptoms in African American children are
associated with both concurrent and long-term academic, social, and psychological
difficulties.
PMID- 17041930
TI - Family-based association study of the MTHFR polymorphism C677T in the bladder
exstrophy-epispadias-complex.
PMID- 17041931
TI - Further phenotypic and genetic variation in ADULT syndrome.
AB - ADULT (Acro-dermato-ungual-lacrimal-tooth) syndrome is characterized by
ectrodactyly, syndactyly, fingernail and toenail dysplasia, hypoplasia of the
breast and nipple, excessive freckling, lacrimal duct atresia, frontal alopecia,
primary hypodontia, and/or early loss of permanent teeth. It is a rare autosomal
dominant disorder which has been linked to mutation in the p63 gene. The p63 gene
has been described in five overlapping limb malformation syndromes including the
EEC syndrome (ectodermal ectrodactyly clefting). We report on the first case of
ADULT syndrome of a mother and daughter with a new mutation R227Q in exon 6 of
the p63 gene. This has not been previously associated with ADULT syndrome but
only seen in EEC. In addition to the previously reported features of ADULT
syndrome this report also describes some additional findings including
hyperextensibility at the distal interphalageal joints, bilateral thumb
duplication, bifid toenails, symptoms of urinary retention, vesicoureteric
reflux, prominent ears, conductive hearing loss, and an overgrowth of a patch of
hair in the midline of the neck. This report expands the knowledge of genotype
phenotype data on the p63 gene and suggests there may be a considerable overlap
between the EEC syndrome and the ADULT syndrome.
PMID- 17041932
TI - Trismus-pseudocamptodactyly syndrome is caused by recurrent mutation of MYH8.
AB - Trismus-pseudocamptodactyly syndrome (TPS) is a rare autosomal dominant distal
arthrogryposis (DA) characterized by an inability to open the mouth fully
(trismus) and an unusual camptodactyly of the fingers that is apparent only upon
dorsiflexion of the wrist (i.e., pseudocamptodactyly). TPS is also known as Dutch
Kentucky syndrome because a Dutch founder mutation is presumed to be the origin
of TPS cases in the Southeast US, including Kentucky. To date only a single
mutation, p.R674Q, in MYH8 has been reported to cause TPS. Several individuals
with this mutation also had a so-called "variant" of Carney complex, suggesting
that the pathogenesis of TPS and Carney complex might be shared. We screened MYH8
in four TPS pedigrees, including the original Dutch family in which TPS was
reported. All four TPS families shared the p.R674Q substitution. However,
haplotype analysis revealed that this mutation has arisen independently in North
American and European TPS pedigrees. None of the individuals with TPS studied had
features of Carney complex, and p.R674Q was not found in 49 independent cases of
Carney complex that were screened. Our findings show that distal arthrogryposis
syndromes share a similar pathogenesis and are, in general, caused by disruption
of the contractile complex of muscle.
PMID- 17041933
TI - Childhood emotional, physical, and sexual abuse, and diagnoses of depressive and
anxiety disorders in adult psychiatric outpatients.
AB - Although a number of theorists have hypothesized a link between negative
experiences during childhood (e.g., abuse) and the presence of psychopathology in
adults, little is known about the relative specificity of childhood emotional,
physical, or sexual abuse to different forms of psychopathology. In this study,
we hypothesized that adult psychiatric outpatients' reports of childhood
emotional abuse would exhibit a specific relationship with diagnoses of
depression. Analyses partially supported our hypothesis. Specifically, diagnoses
of major depression were significantly more strongly related to reports of
childhood emotional abuse than to physical or sexual abuse. However, the same
effect was observed for social phobia. In addition, patients with major
depression reported equivalent levels of childhood emotional abuse as patients
with social phobia, but lower levels of emotional abuse than those with
posttraumatic stress disorder.
PMID- 17041934
TI - Microdeletion and microduplication 22q11.2 screening in 295 patients with
clinical features of DiGeorge/Velocardiofacial syndrome.
AB - The 22q11.2 region is susceptible to chromosomal rearrangements, leading to
various types of congenital malformation and mental retardation. The most common
anomaly is 22q11.2 microdeletion, associated with DiGeorge/Velocardiofacial
syndrome (DG/VCFS). Recently the microduplication 22q11.2 syndrome has been
identified. Some clinical features in patients with this new chromosomal disorder
present a substantial overlap with DG/VCFS. The aim of this hospital-based study
was to evaluate the incidence of deletions and duplications on 22q11.2 in
patients with DG/VCFS features. We investigated a group of 295 patients with
widely variable manifestations associated with DG/VCFS. Along with the clinical
diagnoses different anomalies were noted such as conotruncal cardiac anomaly,
velopharyngeal insufficiency, characteristic facial dysmorphic features, language
impairment, developmental delay/learning difficulties, and immunologic anomalies
or thymic hypoplasia. Laboratory studies included conventional cytogenetic and
FISH testing. Metaphase and interphase cells were analyzed for the presence of
22q11.2 microdeletion or microduplication. There were 12 patients who carried
22q11.2 microdeletion and no microduplication in the region was identified. Other
chromosomal anomalies were reported in five patients with an overlapped DG/VCFS
phenotype. All patients with 22q11.2 microdeletion showed a characteristic
phenotype of DG/VCFS. We did not identify 22q11.2 microduplication, suggesting
that this is a rare event in patients with DG/VCFS features.
PMID- 17041936
TI - DLL3 as a candidate gene for vertebral malformations.
AB - Investigations have not identified a major locus for congenital vertebral
malformations. Based on observations in mice, we hypothesized that mutations in
DLL3, a member of the notch-signaling pathway, might contribute to human
vertebral malformations. We sequenced the DLL3 gene in 50 patients with
congenital vertebral malformations. A Caucasian male patient with VACTERL
manifestations including a T5-T6 block vertebrae was heterozygous for a "G" to
"A" missense mutation changing glycine to arginine at codon 269. This residue is
conserved in mammals, including chimpanzee, mouse, dog, and rat. Additional
testing in the patient did not show evidence of chromosome abnormalities. The
patient's asymptomatic mother was also heterozygous for the missense mutation.
Since this mutation was not observed in a control population and leads to an
amino acid change, it may be clinically significant. The mutation was not found
in a control population of 87 anonymous individuals. Several established
mechanisms could explain the mutation in both the patient and his asymptomatic
mother (susceptibility allele requiring additional environmental factors, somatic
mosaicism, multigenic inheritance). Documenting the absence of the mutation in a
larger control population or the presence of the mutation in additional affected
patients, or documenting a functional difference in DLL3 would provide further
evidence supporting its causal role.
PMID- 17041937
TI - Tracking rare incidence syndromes (TRIS) project.
PMID- 17041935
TI - Obsessive-compulsive disorder versus body dysmorphic disorder: a comparison study
of two possibly related disorders.
AB - The relationship between obsessive-compulsive disorder (OCD) and body dysmorphic
disorder (BDD) is unclear. BDD has been proposed to be an OCD-spectrum disorder
or even a type of OCD. However, few studies have directly compared these
disorders' clinical features. We compared characteristics of subjects with OCD
(n=210), BDD (n=45), and comorbid BDD/OCD (n=40). OCD and BDD did not
significantly differ in terms of demographic features, age of OCD or BDD onset,
illness duration, and many other variables. However, subjects with BDD had
significantly poorer insight than those with OCD and were more likely to be
delusional. Subjects with BDD were also significantly more likely than those with
OCD to have lifetime suicidal ideation, as well as lifetime major depressive
disorder and a lifetime substance use disorder. The comorbid BDD/OCD group
evidenced greater morbidity than subjects with OCD or BDD in a number of domains,
but differences between the comorbid BDD/OCD group and the BDD group were no
longer significant after controlling for BDD severity. However, differences
between the comorbid BDD/OCD group and the OCD group remained significant after
controlling for OCD severity. In summary, OCD and BDD did not significantly
differ on many variables but did have some clinically important differences.
These findings have implications for clinicians and for the classification of
these disorders.
PMID- 17041938
TI - Frontonasal malformation, first branchial arch anomalies, congenital heart
defect, and severe central nervous system involvement: a possible "new" autosomal
recessive syndrome?
AB - Here we report on a girl presenting with midline cleft lip/palate, prominent
forehead, macrocephaly, first branchial arch anomalies, and tetralogy of Fallot.
Imaging studies showed polymicrogyria, enlarged ventricles with a large cystic
lesion extending postero-superiorly over the cerebellum, abnormally modeled
cerebellum, and congenital aqueductal stenosis. To our knowledge, this
combination of clinical signs involving the frontonasal process, midline lip
clefting, congenital heart malformation, and severe CNS developmental
abnormalities has not previously been reported. Clinical, imaging data, as well
as differential diagnosis are discussed.
PMID- 17041939
TI - Antenatal screening tests: knowledge and practice patterns of obstetricians in
Utah.
AB - We sought to assess knowledge and practices of obstetricians regarding antenatal
testing and test the efficacy of continuing education via a direct mailing. In
June 2004, an educational brochure entitled "New Options for Maternal Serum
Screening for Birth Defects" as well as an anonymous survey pertaining to
antenatal testing was sent to 241 American College of Obstetricians and
Gynecologists (ACOG) Fellows and Junior Fellows residing in Utah. Data from the
85 (35%) respondents were analyzed. The majority of respondents practice
obstetrics (81/85, or 95%). Of these, 67% of respondents perform sonograms
routinely in their offices. Respondents were distributed evenly across all years
of practice. Respondents offer HIV screening routinely (85%), but only 40% follow
ACOG cystic fibrosis (CF) screening recommendations. Midtrimester serum screening
is offered routinely by 89% of the respondents, but only 54% adequately
understood the capabilities and limitations of the test. Questions related to the
patient education brochure included in the mailing were answered correctly more
often than the other questions. The brochure emphasized the usefulness of
combined integrated screening for detecting Down syndrome, and 94% of respondents
subsequently understood this concept. We show that in Utah, ACOG recommendations
for HIV and maternal serum testing are being followed uniformly, but CF screening
is still not being routinely offered. The accurate responses to questions related
to an enclosed education brochure suggest that direct mailings may be useful for
provider education, especially in regions where many providers practice remote
from academic centers.
PMID- 17041940
TI - No association between periconceptional multivitamin supplementation and risk of
multiple congenital abnormalities: a population-based case-control study.
AB - Two previous Hungarian intervention trials showed that periconceptional folic
acid-containing multivitamin supplementation did not change the total (birth +
fetal) prevalence of cases with multiple congenital abnormalities (MCAs).
However, two US observational studies found an elevated risk for MCAs in the
offspring of women who reported periconceptional use of multivitamins containing
folic acid. These conflicting results stimulated us to evaluate the data set of
the Hungarian Case-Control Surveillance of Congenital Abnormalities and to check
the possible association between the use of periconceptional multivitamin
supplementations and the total prevalence of cases with MCAs. Of 1,349 cases with
MCA, 69 (5.1%) had mothers who used multivitamins during the second and third
month of pregnancy. Of 2,405 matched controls without any defect, 126 (5.2%) had
mothers who used multivitamin supplementation in early pregnancy. Of 21,494
malformed controls with isolated congenital abnormalities, 1,052 (4.9%) mothers
received supplementation with multivitamins during the critical period of CAs
including MCAs. There was no difference in the use of multivitamins among the
study groups either in the total data set or at the evaluation of only
prospective medically recorded data. Medically recorded folic acid use without
any multivitamins in the second and third gestational month showed some
protective effect for MCAs. In conclusion, our observational case-control study
did not detect a folic acid containing multivitamins during the early pregnancy
as a risk factor for MCAs.
PMID- 17041941
TI - Genotype-phenotype correlations in cerebral cavernous malformations patients.
AB - OBJECTIVE: To compare clinical features of CCM1, CCM2, and CCM3 mutation
carriers. METHODS: A detailed clinical and molecular analysis of 163 consecutive
cerebral cavernous malformation (CCM) families was performed. RESULTS: A
deleterious mutation was detected in 128 probands. Three hundred thirty-three
mutation carriers were identified (238 CCM1, 67 CCM2, and 28 CCM3). Ninety-four
percent of the probands with an affected relative had a mutation compared with
57% of the probands with multiple lesions but no affected relative (p < 0.001).
The number of affected individuals per family was lower in CCM3 families (p <
0.05). The proportion of patients with onset of symptoms before 15 years of age
was higher in the CCM3 group (p < 0.0025). Cerebral hemorrhage was the most
common initial presentation in CCM3 patients. The average number of T2-weighted
imaging lesions was similar in the three groups, in contrast with a significantly
lower number of gradient-echo sequence lesions in CCM2 patients (p < 0.05). The
number of gradient-echo sequence lesions increased more rapidly with age in CCM1
than in CCM2 patients (p < 0.05). INTERPRETATION: Despite similarities among the
three groups, there is a significantly lower number of affected individuals in
CCM3 pedigrees, CCM3 mutations may confer a higher risk for cerebral hemorrhage,
particularly during childhood, and the increment of gradient-echo sequence
lesions with age differs between CCM1 and CCM2 patients.
PMID- 17041942
TI - RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion
Smith-Magenis syndrome.
AB - Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental
retardation disorder characterized by distinct craniofacial features and
neurobehavioral abnormalities usually associated with an interstitial deletion in
17p11.2. Heterozygous point mutations in the retinoic acid induced 1 gene (RAI1)
have been reported in nine SMS patients without a deletion detectable by
fluorescent in situ hybridization (FISH), implicating RAI1 haploinsufficiency as
the cause of the major clinical features in SMS. All of the reported point
mutations are unique and de novo. RAI1 contains a polymorphic CAG repeat and
encodes a plant homeo domain (PHD) zinc finger-containing transcriptional
regulator. We report a novel RAI1 frameshift mutation, c.3103delC, in a non
deletion patient with many SMS features. The deletion of a single cytosine occurs
in a heptameric C-tract (CCCCCCC), the longest mononucleotide repeat in the RAI1
coding region. Interestingly, we had previously reported a frameshift mutation,
c.3103insC, in the same mononucleotide repeat. Furthermore, all five single base
frameshift mutations preferentially occurred in polyC but not polyG tracts. We
also investigated the distribution of the polymorphic CAG repeats in both the
normal population and the SMS patients as one potential molecular mechanism for
variability of clinical expression. In this limited data set, there was no
significant association between the length of CAG repeats and the SMS phenotype.
However, we identified a 5-year-old girl with an apparent SMS phenotype who was a
compound heterozygote for an RAI1 missense mutation inherited from her father and
a polyglutamine repeat of 18 copies, representing the largest known CAG repeat in
this gene, inherited from her mother.
PMID- 17041944
TI - Age-dependent decreases in mitogen-stimulation level and RNA content in
peripheral blood mononuclear cells of Down syndrome patients.
AB - OBJECTIVE: The aim of the present study was to determine whether or not the
phytohemagglutinin (PHA)-activated proliferation and average RNA content in
peripheral blood mononuclear cells (PBMC) of Down syndrome (DS) patients change
with age. METHOD: Stimulated portion of PBMC and total RNA levels in these cells
after 72 h of PHA stimulation from 38 DS patients were compared with 28 age
matched healthy controls using flow cytometric measurement. RESULTS: Decreased
ratio of PBMC from DS patients undergoes mitogenic stimulation with age (r =
0.84, P = 0.000). This decrease is not observed in the cells of control
individuals (r = 0.03, P = 0.869). Stimulated PBMC in infants with DS have higher
level of RNA contents compared to controls (Z = 2.227, P = 0.026). While RNA
content in mitogen-stimulated PBMC of DS decreased progressively and
significantly with age (r = -0.70, P = 0.000), no significant age-related change
in RNA content was found among the cells of healthy individuals in the range of 0
27 year old (r = 0.275, P = 0.157, P > 0.05). CONCLUSION: Age-dependent decreases
in mitogen-activated proliferation ratio and average RNA content of PBMC from DS
patients appear as regular events. These results may contribute to the
explanation of the immune deficiency seen in DS patients since the PHA-stimulated
cells are principally T-lymphocytes. This is the first report on the decrease in
PHA-stimulated proliferation ratio (stimulability) and RNA level in PBMC of DS
patients in relation to age.
PMID- 17041943
TI - DNA sequence analysis of GJB2, encoding connexin 26: observations from a
population of hearing impaired cases and variable carrier rates, complex
genotypes, and ethnic stratification of alleles among controls.
AB - Mutations in GJB2 are associated with hereditary hearing loss. DNA sequencing of
GJB2 in a cohort of hearing impaired patients and a multi-ethnic control group is
reported. Among 610 hearing impaired cases, 43 DNA sequence variations were
identified in the coding region of GJB2 including 24 mutations, 8 polymorphisms,
3 unclassified variants (G4D, R127C, M163V), 1 controversial variant (V37I), and
7 novel variants (G12C, N14D, V63A, T86M, L132V, D159,
592_600delinsCAGTGTTCATGACATTC). Sixteen non-coding sequence variations were also
identified among cases including the IVS1+1A>G mutation, 2 polymorphisms, and 13
novel variants. A diagnosis of GJB2-associated hearing loss was confirmed for 63
cases (10.3%). Heterozygous mutations were found in 39 cases (6.4%). Eleven cases
carrying novel or unclassified variants (1.8 %) and 18 cases carrying the
controversial V37I variant were identified (3%). In addition, 294 control
subjects from 4 ethnic groups were sequenced for GJB2. Thirteen sequence
variations in the coding region of GJB2 were identified among controls including
2 mutations, 6 polymorphisms, 2 unclassified variants (G4D, T123N), 1
controversial variant (V37I), and 2 novel variants (R127L, V207L). Nine sequence
variations were identified among controls in the non-coding regions in and around
GJB2 exon 2. Of particular interest among controls were the variability in
carrier rates and ethnic stratification of alleles, and the complex genotypes
among Asians, 47% of whom carried two to four sequence variations in the coding
region of GJB2. These data provide new information about carrier rates for GJB2
based hearing loss in various ethnic groups and contribute to evaluation of the
pathogenicity of the controversial V37I variant.
PMID- 17041945
TI - HIV-1-infected children on HAART: immunologic features of three different levels
of viral suppression.
AB - BACKGROUND: HIV-1-infected children show changes of blood lymphocyte
subpopulations. We have, therefore, investigated how highly active anti
retroviral therapy (ART) alter these subsets. Blood samples were taken from 41
HIV-1-infected children on ART who were divided into groups showing good, partial
and poor responses to ART on the basis of viral load (VL) measurement in blood.
The observations were compared to those seen in 20 uninfected children. METHODS:
The samples were studied using 4-color flow cytometry for "naive", central memory
and effector memory cells as well as for CD38 expression as the sign of
activation within both the CD4+ and the CD8+ T cell populations. HIV-1 infected
children were also evaluated for the presence and the titers of antibodies
induced by vaccination against childhood infections in our patients while on
HAART. RESULTS: Lymphocyte counts were lower in the "poor" viral load responding
(VLR) group when compared with partial and good VLRs. Poor VLRs had lower total
and naive CD4+ T cell counts. HIV-1-infected children from all three groups had
high CD8+ T cell counts. Central memory CD4+ and CD8+ T cell percentages were
particularly low in the poor VLR group while in the poor VLR group the
percentages of effector memory CD4+ and CD8+ T cells were higher when compared
with the control group. Higher cellular activation of CD8+ T cells was observed
in HIV-1-infected children, particularly when analyzed for the intensity of CD38
expression in the poor VLR group. CD5 expression on B cells was higher among all
HIV-1-infected children. Antibodies to tetanus, diphtheria, measles, rubella, and
hepatitis B were present in a large proportion of children but the titers were
similarly low for all three groups of HIV-infected children. CONCLUSIONS:
Children with different levels of viral response to HAART present immune
phenotype characteristics that tend to place the children with partial and good
virological responses into the same group. These children are still moderately
deficient in their immune responses but show better recovery than seen with
children in the poor VLR group. These observations indicate that the proportions
of central memory cells among the CD4+ T cells and the intensity of the
expression of CD38 activation antigen on CD8+ T cells provide more informative
parameters for monitoring children on HAART than the absolute numbers of CD4+ and
CD8+ T cells alone.
PMID- 17041946
TI - National standardization of ZAP-70 determination by flow cytometry: the French
experience.
AB - BACKGROUND: ZAP-70, after being considered as a potential surrogate for VH
mutational status, has seen its own prognostic value emerge. We aimed at
standardizing a simple, fast, and reproducible flow cytometry method. METHODS:
AntiZAP-70 antibody 2F3.2 was used with indirect labeling and secondary anti
IgG2a antibody. The reference values for the expression of the results were
determined on 45 normal blood samples. ZAP-70 protein expression was investigated
in 192 CLL samples. The indirect technique was compared with FITC-conjugated
2F3.2 clone, and with clone 1E7.2-FITC, -PE or -AlexaFluor 488. RESULTS: Using
FITC or PE-conjugated antibodies, 2F3.2 and 1E7.2 clones allowed a much less
adequate discrimination between positive and negative cells and discordant cases
were most likely true negative cases. Using the AlexaFluor 488 conjugated 1E7.2
clone, the discordant cases were mostly negative with the conjugated antibody and
positive with the 2F3.2 clone but Western blotting or RNA microarray confirmed
discordant cases were false negative with the conjugated antibody. Subsequently,
recommendations were used by 13 centers participating in an interlaboratory
quality control protocol. The use of MFI ratio appeared to be more reliable.
CONCLUSIONS: Results suggested that slight differences in the procedure had
little impact on the interpretation in characteristic cases; however, careful
interpretation was required for values close to threshold.
PMID- 17041947
TI - Fluoxetine treatment increases trabecular bone formation in mice.
AB - Mounting evidence exists for the operation of a functional serotonin (5-HT)
system in osteoclasts and osteoblasts, which involves both receptor activation
and 5-HT reuptake. In previous work we showed that the serotonin transporter (5
HTT) is expressed in osteoclasts and that its activity is required by for
osteoclast differentiation in vitro. The purpose of the current study was to
determine the effect of treatment with fluoxetine, a specific serotonin reuptake
inhibitor, on bone metabolism in vivo. Systemic administration of fluoxetine to
Swiss-Webster mice for 6 weeks resulted in increased trabecular BV and BV/TV in
femurs and vertebrae as determined by micro-computed tomography (microCT). This
correlated with an increase in trabecular number, connectivity, and decreased
trabecular spacing. Fluoxetine treatment also resulted in increased volume in
vertebral trabecular bone. However, fluoxetine-treated mice were not protected
against bone loss after ovariectomy, suggesting that its anabolic effect requires
the presence of estrogen. The effect of blocking the 5-HTT on bone loss following
an LPS-mediated inflammatory challenge was also investigated. Subcutaneous
injections of LPS over the calvariae of Swiss-Webster mice for 5 days resulted in
increased numbers of osteoclasts and net bone loss, whereas new bone formation
and a net gain in bone mass was seen when LPS was given together with fluoxetine.
We conclude that fluoxetine treatment in vivo leads to increased bone mass under
normal physiologic or inflammatory conditions, but does not prevent bone loss
associated with estrogen deficiency. These data suggest that commonly used anti
depressive agents may affect bone mass.
PMID- 17041948
TI - Improvement of diagnostic accuracy and screening conditions with liquid-based
cytology.
AB - The aim of this population-based study was to compare the histological follow-up
diagnoses of cervicocytological neoplasia (dysplasia, carcinoma in situ and
carcinoma) in conventional Papanicolaou (CP) smear and ThinPrep PapTest samples
(TP). All cytological samples from the County of Funen, Denmark, in the periods
2000 (n = 34,832) and 2002 (n = 29,995) were included in the study. In 2000 and
2002, the specimens were CP and TP, respectively. The detection rate of > or =
mild dysplasia was 0.8% in CP and 1.4% in TP, showing a 75% increase in TP when
compared with CP (p < 0.001). Histological follow-up of > or = moderate dysplasia
revealed a neoplastic lesion in 77.1% and 87.9% in CP and TP, respectively (P <
0.001). The present study indicates that the diagnostic accuracy of cervical
cytology is improved with liquid-based cytology. In addition, we focus on the
optimized cellular material that shows the diagnostic details very clearly to the
microscopist and leads to radically improved screening conditions.
PMID- 17041949
TI - Salivary gland crystalloids.
PMID- 17041950
TI - Fine needle aspiration cytology of lipomatous lesions of the thyroid.
PMID- 17041951
TI - Fine-needle aspiration cytology of an intrathyroid parathyroid adenoma.
PMID- 17041952
TI - Pneumatosis cystoides intestinalis--is it possible to diagnose it by fine-needle
aspiration cytology?
PMID- 17041953
TI - Pancreatic mucinous lesions: a retrospective analysis with cytohistological
correlation.
AB - The diagnosis of mucinous pancreatic lesions, which include mucinous noncystic
adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic
neoplasm (MCN), and mucinous metaplasia, is critical, given different clinical
management and prognosis. This retrospective study is done to assess the
cytological features and pitfalls associated with these entities in cytological
samples.A search for pancreatic cytology specimens with histological confirmation
of the various pancreatic mucinous lesions was done from 1988 to 2005: 9 mucinous
adenocarcinoma, 14 IPMN, 11 MCN, and 3 mucinous metaplasia. The majority (35/37)
had been endoscopic ultrasound-guided fine-needle aspirations. The cellularity,
background extracellular mucin, epithelial architecture, mucinous nature of the
epithelium, cell shape, and nuclear features were evaluated on the cytology
material. Of the 22 cytological features evaluated, the presence of three
dimensional clusters, micropapillary structures, and nuclear atypia, which
includes nuclear crowding, increased N/C ratio, anisonucleosis, nuclear membrane
contour irregularity, clumpy chromatin, and prominent nucleoli, was found to be
consistently associated with mucinous adenocarcinoma. There were no statistically
significant cytological features, which helped in differentiating IPMN, MCN, and
mucinous metaplasia. There was a relatively high false-positive rate in the IPMN
group (5/14, 36%). Review of the histological specimen showed severe dysplastic
epithelial change in these cases. One false-positive case of mucinous metaplasia
(1/3, 33%) showed marked intraepithelial acute inflammation. The cytological
diagnosis of mucinous pancreatic lesions remains challenging, except for mucinous
noncystic adenocarcinoma. The findings were largely nonspecific in the
differentiation between IPMN, MCN, mucinous metaplasia, and incidentally sampled
gastrointestinal epithelium. False-positive diagnosis of adenocarcinoma occurs
not infrequently in the setting of IPMN with severe dysplastic epithelial change
and in lesions with associated acute inflammation, and can be a pitfall in the
diagnosis of these lesions.
PMID- 17041954
TI - Utility of reflex Gomori methenamine silver staining for Pneumocystis jirovecii
on bronchoalveolar lavage cytologic specimens: a review.
AB - Pneumocystis jiroveci (Pj; formerly Pneumocystis carinii) is an opportunistic
pathogen causing life-threatening pneumonia (Pneumocystis pneumonia) in
immunosuppressed individuals. Its diagnosis is dependent on identification in
bronchoalveolar lavage (BAL) specimens. Gomori's methenamine silver nitrate (GMS)
stain has been advocated to highlight the organisms in BAL specimens. This study
was performed to determine the utility of reflex GMS staining on all BAL
specimens for identifying Pj.All BAL specimens from years 2000 to 2004 were
processed as cytospins and stained with Papanicolaou (Pap) and GMS stains. A
total of 2,984 BAL specimens were identified. A total of 116 (3.9% of total BAL)
BAL specimens were diagnostic of Pj. The diagnostic specimens were grouped as
follows: 103 (88.8% of total positive cases) Pj identified with both Pap and GMS
staining; 11 (9.5% of total positive cases) Pj identified only with Pap staining;
and 2 (1.7% of total positive cases) Pj identified only with GMS staining. In
conclusion, the prevalence of Pj in BAL specimens is 3.9%, which can be
attributed to improved management of immunocompromised patients. Performing
reflex GMS staining on all BAL specimens does not improve the diagnostic
identification of Pj since the majority (98.3%) of diagnoses can be rendered on
Pap stained slides. A cost analysis for GMS staining on 2,879 GMS-negative BAL
specimens was estimated at $143,950. Thus, from diagnostic and cost benefit
perspectives, GMS staining can be recommended only on cases where Pap stain is
negative, and the clinical presentation is consistent with Pneumocystis
pneumonia.
PMID- 17041955
TI - ASC-US and high-risk HPV testing: performance in daily clinical practice.
AB - Data are beginning to accrue on high-risk HPV DNA testing in patients with ASC-US
on cervical cytology. We report on our experience at the University of Wisconsin
Hospital and Clinics. From February 2002 through December 31, 2005 (3 yr, 11 mo),
the cytopathology laboratory processed 49,599 Pap Tests, of which 1,792 (3.6%)
were diagnosed as ASC-US. Six hundred and seventy two (37.5%) of these cases were
processed for high-risk HPV genotypes using the Digene Hybrid Capture II method.
Of these cases, 266 (39.6%) were positive for high-risk HPV genotypes, 11 (1.6%)
were equivocal, and 395 (58.8%) were negative. Biopsy follow-up was available for
127 (47.7%) of the 266 cases, of which 66 (52%) were negative, 46 (36.2%) showed
CIN I, 9 (7.1%) were CIN II, and 6 (4.7%) were CIN III. Of the remaining 139
(52.3%) cases, 86 (62%) had follow-up Pap Tests, of which 57 (66.3%) were
negative, 15 (17.4%) were ASC-US, 12 (15%) were low-grade squamous
intraepithelial lesions, and 2 (2.3%) were high-grade squamous intraepithelial
lesions; 53 (38.1%) were lost to follow-up. In combination, 90 (42.25%) of the
213 cases with follow-up showed atypia or above after a diagnosis of ASC-US; of
which 58 (64%) were low-grade lesions and 17 (19%) were high-grade lesions. Our
laboratory's reported high-risk HPV positivity is comparable to recent reports in
the literature on its use in daily clinical practice. In addition, cervical
abnormalities were found in a significant proportion of the cases.
PMID- 17041956
TI - Cost efficiency analysis for fine-needle aspiration in the workup of parotid and
submandibular gland nodules.
AB - The utility and cost effectiveness of salivary gland fine-needle aspiration (FNA)
is controversial. Some authorities argue FNA has no added value over clinical
radiographic study because most salivary gland nodules occur in the parotid and
the tumor's relationship to the facial nerve determines the operative procedure
rather than the histology. Other experts contend FNA is of value by reducing the
overall number of operative procedures performed. We studied 306 salivary gland
nodules (214 parotid and 92 submandibular gland) undergoing FNA. One hundred and
seventy one were subsequently surgically resected and the remaining 135 followed
clinically. A 16% error rate was associated with the nonoperative group,
necessitating later surgical resection. The cost of the FNAs and surgical
resections (when performed) was calculated based on Medicare reimbursement rates.
Costs were based on all cases undergoing initial FNA. The expense of initial
resection was based on the observed percentage of patients undergoing resection
in our series. The costs of resections related to erroneous FNA diagnoses were
based on the error rate associated with FNA diagnoses clinically followed (i.e.,
chronic sialadenitis). Costs of FNAs, initial resections, and subsequent
resections related to FNA errors were summed and compared with the cost which
would have occurred if all nodules had been primarily resected.FNA reduced the
number of operative procedures by approximately 65% for submandibular nodules and
35% for parotid nodules. Diagnoses which resulted in nonsurgical management
included chronic radiation-induced sialadenitis, intraparotid lymph node,
recurrent lymphoma, and accessory nodules or lobes of the parotid gland. Pure
surgical management was associated with a cost of $275,750.00 per 100 patients.
FNA management was associated with an expenditure of $206,632.00 per 100
patients, representing a savings of $69,118.00 (33% savings over surgical
management alone). Based on these data, FNA appears to be cost effective in
addition to supplying preoperative diagnoses helpful in counseling, operative
planning, and allaying patient anxiety.
PMID- 17041957
TI - Upregulation of telomerase (hTERT) is related to the grade of cervical
intraepithelial neoplasia, but is not an independent predictor of high-risk human
papillomavirus, virus persistence, or disease outcome in cervical cancer.
AB - Telomerase activation and telomere maintenance are essential for cell
immortalization and represent a rate-limiting step in cancer progression. The E6
oncoprotein of high-risk human papillomavirus (HPV) is known to activate
telomerase, but its expression in CIN lesions and its prognostic value in
cervical cancer (CC) are still incompletely understood. As part of our HPV
PathogenISS study, a series of 150 CCs and 152 CIN lesions were examined using
immunohistochemical (IHC) staining for hTERT (telomerase reverse transcriptase),
and tested for HPV using PCR with three primer sets (MY09/11, GP5(+)/GP6(+),
SPF). Follow-up data were available from all SCC patients, and 67 CIN lesions had
been monitored with serial PCR for HPV after cone treatment. Expression of hTERT
was increased in parallel with the grade of CIN, with major up-regulation upon
transition to CIN3 (OR 18.81; 95% CI 8.48-41.69; P = 0.0001). Positive hTERT
expression was 90% specific indicator of CIN, with 98.7% PPV, but suffers from
low sensitivity (57.5%) and NPV (14.3%). hTERT expression was also significantly
associated to HR-HPV with OR 3.38 (95% CI 1.90-6.02; P = 0.0001), but this
association was confounded by the histological grade (Mantel-Haenszel common OR =
1.83; 95% CI 0.92-3.79; P = 0.086). Expression of hTERT did not predict
clearance/persistence of HR-HPV after treatment of CIN, and it was not a
prognostic predictor in cervical cancer in univariate or multivariate survival
analysis. It was concluded that up-regulation of hTERT was closely associated
with HR-HPV, due to activation by the E6 oncoprotein. hTERT is a late marker of
cervical carcinogenesis, significantly associated with progression to CIN3.
Theoretically, a combination of hTERT assay (showing high SP and PPV) with
another test showing high SE and high NPV (e.g. Hybrid Capture 2 for HPV), should
provide an ideal screening tool capable of high-performance detection of CIN
lesions.
PMID- 17041958
TI - Fine-needle aspiration biopsy findings in epithelioid myoepithelioma of the
parotid gland: a case report.
AB - We describe the fine-needle aspiration biopsy findings in a case of epithelioid
myoepithelioma of the parotid gland in a 24-yr-old male. The cytologic features
of myoepithelioma of the parotid gland are only documented in a few case reports
and we believe the cytologic description of the epithelioid variant has been
described in only one other case. The differential diagnosis with other salivary
gland neoplasms is discussed.
PMID- 17041959
TI - Bioremediation potential of live and dead Spirulina: spectroscopic, kinetics and
SEM studies.
AB - Metal binding by algae has enormous potential for environmental bioremediation
targeting towards detoxification of water bodies. The present work reports the
use of live and dead Spirulina sp. for sorption of metals like Cr(3+), Ni(2+),
Cu(2+), and Cr(6+) in form of Cr(2)O(7)(2-). Preliminary investigation shows that
this biomass takes up substantial amount of metal ions indicated above. IR
spectroscopic study, kinetics models, Langmuir and Freundlich adsorption
isotherms, SEM analysis, and fluorescence microscopic study of Spirulina sp. and
the Spirulina sp. treated with different metal ions have been employed to
understand the sorption mechanism. It is hoped that live Spirulina sp. will be a
strong candidate for management of industrial wastewater.
PMID- 17041960
TI - Immunological characterization of a newly developed antibody for localization of
a beta-keratin in turtle epidermis.
AB - Turtle scutes are made of hard (beta)-keratins. In order to study size and
localization of beta-keratins in turtle shell, we produced a rat polyclonal
antiserum against a turtle scute beta-keratin of 13-16 kDa, which allowed the
immunolocalization of the protein in the epidermis. In immunoblots the antiserum
recognized turtle beta-keratins but showed variable cross-reactivity with lizard,
snake, and avian beta-keratins. The turtle antiserum appears less cross-reactive
than a chicken scale antiserum (Beta-1). In bidimensional immunoblots, three main
protein spots at 15-16 kDa with pI at 7.3, 6.8, 6.4, and an unresolved large spot
at 40-45 kDa with pI around 5 were more constantly obtained. The latter may
result from the aggregation of the smaller beta-keratin protein. The corneous
layer of the carapace and plastron of various species of chelonians appeared
immunofluorescent. The ultrastructural immunolocalization showed sparse labeling
over beta-keratin filaments of cells of the horny layer of both carapace and
plastron. The study for the first time shows that the isolated protein band
derived from a component of the beta-keratin filaments of the corneous layer of
turtles. This antibody can be used for further studies on beta-keratin expression
and sequencing in chelonian shell. No labeling was present over other cell
organelles or layers of turtle epidermis and it was absent in non-epidermal
cells. The specificity for turtle beta-keratin suggests that the antiserum
recognizes some epitope/s specific for chelonians beta-keratins, and that it also
variably recognizes other reptilian and avian beta-keratins.
PMID- 17041961
TI - Germ cell depletion does not alter the morphogenesis of the fetal testis or ovary
in the red-eared slider turtle (Trachemys scripta).
AB - In the red-eared slider turtle, Trachemys scripta, both prospective male and
female gonads contain primitive cord structures at the time when the gonad first
forms. Primordial germ cells arrive in the gonad and accumulate on the coelomic
surface. If testis development is initiated, these cords develop further at the
same time that germ cells migrate from the coelomic surface and become
sequestered in the interior of the cords. In contrast, in the developing ovary
germ cells proliferate in a defined cortical domain, while the primitive cords
regress and form flattened lacunae in the medulla. Because of their intimate
association with these developmental processes, we investigated whether germ
cells were required in turtles to establish the morphology of the fetal testis
and ovary. We present evidence that normal morphological development of the fetal
gonad occurs in both sexes in T. scripta after germ cell depletion, suggesting a
conservation of developmental mechanisms across vertebrates.
PMID- 17041963
TI - The objectives and work of the National Rheumatoid Arthritis Society.
PMID- 17041964
TI - Overview of the psychosocial concerns of young adults with juvenile arthritis.
AB - Young adults who develop juvenile idiopathic arthritis in childhood have a
significant risk of long-term morbidity and continuing disease activity in
adulthood. The impact of a physically restricting and painful chronic illness can
make the transition from adolescence to adulthood more challenging. In this
overview of the psychological and social impact of juvenile arthritis on young
adults, particular attention is given to those areas that are of concern to this
age group. The transition from adolescence to adulthood can be detrimentally
affected not only by the attitudes of peers and parents, but also by the
attitudes of the individual with arthritis. Chronic arthritis, including juvenile
arthritis, is related to increased rates of anxiety and depression. In the face
of functional restriction, pain, and poor body image, social and sexual
relationships may be harder to develop and maintain. The family of the young
adult may also be affected on many levels. Employment and financial security are
common and well-founded concerns of young disabled adults.
PMID- 17041962
TI - Expression profiling of BEN regulated genes in mouse embryonic fibroblasts.
AB - BEN is a member of the TFII-I family of helix-loop-helix transcription factors.
Both TFII-I and BEN are involved in gene regulation through interactions with
tissue-specific transcription factors and chromatin remodeling complexes.
Identification of the downstream target genes of TFII-I proteins is critical in
delineating the regulatory effects of these proteins. In this study, we conducted
a microarray analysis to determine gene expression alterations following the
overexpression of BEN in primary mouse embryonic fibroblasts (MEFs). We found the
BEN-dependent modulation in the expression of large groups of genes representing
a wide variety of functional categories including genes important in the immune
response, cell cycle, transcriptional regulation and cell signaling. A set of
genes identified by the microarray analysis was validated by independent real
time PCR analysis. Among upregulated genes were Shrm, Tgfb2, Ube2l6, G1p2, Ccl7
while downregulated genes were Folr1, Tgfbr2, Csrp2, and Dlk1. These results
support a versatile function of TFII-I proteins in vertebrate physiology and lead
to an increased understanding of the BEN-dependent molecular events.
PMID- 17041965
TI - Being a parent or grandparent with back pain, ankylosing spondylitis or
rheumatoid arthritis: a descriptive postal survey.
AB - Research that explores being a parent or grandparent with musculoskeletal
problems has been fairly limited to date. The aim of this study was to describe
the experience of parenting in the context of back pain (BP), ankylosing
spondylitis (AS) and rheumatoid arthritis (RA), with a particular focus on the
extent and nature of childcare experiences and to compare these experiences
across the three groups. In addition, the possible reasons for these reported
experiences, the availability of advice and support and the development of
strategies for coping were explored using a cross-sectional descriptive survey. A
total of 448 participants was recruited from relevant charitable organizations
and the National Health Service (280 with BP, 106 with AS and 62 with RA). A
combination of opportunistic and random sampling was used. Quantitative data were
analysed with appropriate descriptive and inferential statistics using
Statistical Package for the Social Sciences (SPSS version 10). Qualitative data
were analysed using content analysis. Results indicate that a high proportion of
all groups experienced a wide range of difficulties with parenting (81% BP, 77%
AS, 97% RA). The most prevalent problems were similar for all three groups:
lifting baby/child from the floor or cot, encouraging children/grandchildren to
help with domestic chores and keeping up (in terms of energy) with
children/grandchildren. However, the RA group reported having greater
difficulties than the other two groups. Very little advice was offered to
participants with parenting difficulties which may indicate a gap in service
provision. However, a wide range of strategies for coping were described by
respondents. The study highlighted a need for healthcare professionals to develop
a greater awareness of parenting issues and to provide opportunities for these
issues to be addressed.
PMID- 17041966
TI - A review of the history of hand exercises in rheumatoid arthritis.
AB - The management of the hand in the patient with rheumatoid arthritis (RA) is a
challenge to all therapists and evidence for optimum management historically
scarce. Given that it is estimated that hands and wrists are affected in 80-90%
of RA patients (Maini and Feldmann, 1998), it is apparent that this is an
important area for both the patient and practitioner. While acknowledging the
importance of hand function to the patient with RA (Jones et al., 1991), it
should also be admitted that there is little research evidence relating to the
conservative management of hand function in this patient population. This paper
reviews the research that has been carried out in this area and explores possible
areas for further research.
PMID- 17041967
TI - An exploration of patients' experiences of anti-TNF therapy.
AB - OBJECTIVE: To explore the experience of rheumatoid arthritis patients receiving
anti-tumour necrosis factor (anti-TNF) therapy on physical, psychological and
social well-being. METHOD: Seven patients with rheumatoid arthritis (RA) who
received six months of infliximab were interviewed in depth by one researcher to
identify their experiences of this treatment. The interviews were tape-recorded
and analysed using Colaizzi's procedural steps. RESULTS: Four main categories
were identified from the interview relating to the patient's experience of anti
TNF therapy. These included: The impact of living with RA on physical,
psychological and social function. The influence of anti-TNF therapy on physical,
psychological and social function. The experience of attending for treatment. The
impact of discontinuing anti-TNF treatment. CONCLUSION: All seven patients
experienced benefits from receiving anti-TNF therapy. These benefits were not
maintained once the treatment period was completed.
PMID- 17041968
TI - Biologic agents used to treat rheumatoid arthritis and their relevance to
podiatrists: a practice update.
AB - This review considers the pharmacological management of rheumatoid arthritis
including the role of anti-tumour necrosis factor alpha (TNFalpha) agents, as a
precursor to highlighting some of the issues for podiatrists involved in the care
of patients on this particular medication.
PMID- 17041969
TI - Should nurses be screening for ischaemic heart disease in nurse-led rheumatoid
arthritis clinics?
PMID- 17041970
TI - Nurse prescribing in rheumatology: a case study.
AB - This case study outlines the clinical management, and in particular the drug
management, of a patient with polymyalgia rheumatica (PMR) in secondary care. The
lady in question, Mrs Adams (pseudonym as per NMC Guidelines), is under the care
of the consultant rheumatologist. Within this clinical setting, and in
conjunction with an appropriate, agreed clinical management plan, this paper
demonstrates that the nurse consultant can effectively manage Mrs Adams' care and
treatment.
PMID- 17041971
TI - Practice development: an important component of the clinical nurse specialist
role.
PMID- 17041972
TI - Pain mechanisms and the rheumatic diseases.
AB - Pain is the predominant complaint of those with a rheumatological condition. This
paper provides a broad overview of the current theories on the mechanisms of
pain, the structure of the nervous system, and how these may relate to the
sometimes seemingly incomprehensible symptoms of pain and other sensory
disturbances that some rheumatology patients describe. Three case histories
relating to rheumatoid arthritis, osteoarthritis and fibromyalgia are used to
illustrate how this knowledge can be applied to clinical practice.
PMID- 17041973
TI - Drug treatment for fibromyalgia.
AB - The term 'fibromyalgia' probably covers a variety of diagnoses for which we have
no formal diagnostic tests. Nevertheless, it remains a cause of discomfort and
disability, often amenable to non-drug treatment that should always be tried
first. This article reviews the different drug treatments available that are of
interest to the rheumatology community because the drugs that often procure pain
relief are not always the same as those that are conventionally used for
degenerative or inflammatory polyarthritis. This, in turn, may provide a clue to
causation.
PMID- 17041975
TI - Towards multidisciplinary teamworking in musculoskeletal care: evolution of a
service.
PMID- 17041974
TI - Occupational balance of women with rheumatoid arthritis: a qualitative study.
AB - OBJECTIVE: Occupational balance has been shown to be an important factor in
maintaining health. Rheumatoid arthritis (RA) reduces functional ability and
quality of life and may thus reduce occupational balance. The aim of this
qualitative pilot study was to explore occupational balance in women who have RA.
METHODS: Nine women with RA with past, but not current, paid work experience, no
other confounding neuro-motor disease and with disease duration of 0.75-31 years
were selected from an Austrian rheumatology outpatient clinic. Age range of the
participants was 28-68 years. A semi-structured interview was conducted with each
participant and transcribed verbatim. Data were analysed by the constant
comparative method from an occupational perspective. RESULTS: Three main
categories emerged: (1) The participants experienced a process of change that
affected their occupational balance. (2) This new state of occupational balance
was characterized by changed levels of involvement in physical, mental, social
and rest occupations and by a certain level of unpredictability of symptoms. (3)
Overall, the new state of occupational balance was valued differently:
positively, indifferently or negatively. CONCLUSION: RA was found to have a
considerable impact on occupational balance. The experience is not invariably
seen as negative as previous literature would suggest. Further research should
explore the longitudinal dimension of occupational balance in people with RA.
PMID- 17041976
TI - Rheumatology telephone advice lines.
PMID- 17041977
TI - Cannulation: professional needs and patient experiences.
PMID- 17041978
TI - Rehabilitation in rheumatoid arthritis: a critical review.
AB - This article considers the evidence for effectiveness and timing of
rehabilitation for people with rheumatoid arthritis (RA). The Cochrane Library,
DARE, Medline, Embase, CINAHL and AMED were searched to identify systematic
reviews and randomized controlled trials evaluating rehabilitation interventions
for people with rheumatoid arthritis. Many trials identified had methodological
limitations (e.g. short follow-up periods, small sample sizes). Evidence to date
is that symptomatic relief results from thermotherapy, laser therapy, acupuncture
and assistive devices. In the short-term, comprehensive occupational therapy (in
established rheumatoid arthritis), orthoses, and mind-body approaches can help
maintain function. Over at least a one-year period, the following are effective
in reducing pain and maintaining function: patient education and joint protection
training using behavioural approaches; dynamic exercise therapy, hand exercises
and hydrotherapy; and cognitive-behavioural therapy (in people with poorer
psychological status). Many trials have recruited people with moderate to severe,
established RA and relatively little is known about the long-term effectiveness
of early rehabilitation, although this is becoming much more common in practice.
Despite the increased availability of guidelines and systematic reviews, most
conclude there is insufficient evidence for many areas of rheumatology
rehabilitation. Further well-designed clinical trials are needed recruiting
people with early disease using patient-centred outcomes.
PMID- 17041979
TI - Long-term influences of a biopsychosocial rehabilitation programme for chronic
pain patients.
AB - OBJECTIVE: Chronic pain leads to high costs in the form of compensation for
absence from work due to illness, production loss and health care utilization.
Multidisciplinary treatment programmes at pain clinics can result in return to
work and a decrease in doctor visits. The aim of this study was to evaluate the
long-term influences of a rehabilitation programme in primary health care for
chronic pain patients with regard to doctor visits, frequency of sick-leave and
level of disability. DESIGN: A longitudinal, intervention study design was used
over a three-year period. METHODS: A biopsychosocial rehabilitation programme
based on ego-strengthening psychotherapy was used. An occupational therapist and
a physiotherapist led the intervention, which comprised two meetings per week for
six weeks. The study was performed in a primary health care area in the southwest
of Sweden with 54 chronic pain patients. RESULTS: The results showed a
significant decrease in the number of doctor visits as well as sick-leave days.
The level of absenteeism due to occupational disability changed significantly
from being on sick leave to receiving a disability pension. CONCLUSIONS: The
rehabilitation programme reduced patient attendance at health care facilities but
did not increase the numbers of patients returning to work.
PMID- 17041980
TI - Patients' perspectives on self-management following a back rehabilitation
programme.
AB - OBJECTIVE: The management of chronic low back pain (CLBP) is becoming
increasingly demanding upon health care services and society. Programmes
combining exercise, education and a biopsychosocial approach have become a
popular way of managing CLBP. Programmes are designed to change behaviour,
increase activity levels and encourage self-management. Patients' experiences of
attending a back rehabilitation programme were examined. METHODS: This study used
a qualitative approach combining interviews, non-participant observation and
evaluation of documentation to establish the patients' perspective of self
management following a back programme. RESULTS: All the patients (n = 6 )
indicated they were self-managing by continuing to exercise and utilizing the
advice given after attendance. Two patients felt they should continue attending
the therapy department to exercise in order to gain benefit, demonstrating
reliance on continued health care support. Obstacles to continuing with exercise
were cited as pain, time, and family constraints. Patients also expressed
limitations following attendance regarding the type and level of activity their
CLBP would allow them to manage. The data suggested activity limitation was
inadvertently reinforced by the therapists during the sessions, in the programme
letter and by the patients' existing beliefs regarding the cause of their CLBP.
CONCLUSION: The study demonstrated the importance of understanding patients'
beliefs and expectations prior to a back programme and accounting for these
during attendance. This study also highlighted that all heath care professionals
should be aware of the impact of the language and terminology used when working
with CLBP patients.
PMID- 17041981
TI - Complex interventions.
PMID- 17041982
TI - Ankylosing spondylitis: clinical update.
PMID- 17041983
TI - The role of social comparison in coping with rheumatoid arthritis: an interview
study.
AB - OBJECTIVE: This study aimed to explore the effects of participants' perceptions
of support, ways of coping and feelings of control, on their accounts of well
being. METHODS: Semi-structured interviews were conducted with 10 patients with
rheumatoid arthritis (RA) and explored the dynamics of participants' accounts of
coping with their everyday lives. RESULTS: Four categories of coping mechanisms
were evident in all participants' accounts: support during the medical
consultation, nurse support, social support, and comparative strategies. This
paper focuses on just one of the themes that emerged from our analysis. Further
insight into coping mechanisms was provided by the prevalence of comparative
coping strategies. A comparison with previous disease states was used by every
participant. This comparison enhanced their sense of control and fostered a sense
of well-being. Social comparison was used by seven participants to show
themselves how fortunate they were in relation to others with RA. CONCLUSION:
Comparative coping has been identified as an important strategy adopted by these
participants that could be explored in further intervention-based studies of
coping.
PMID- 17041984
TI - The impact of group education on participants' management of their disease in
lupus and scleroderma.
AB - OBJECTIVES: The aim of this study was to investigate the impact of the pilot
education programmes, entitled 'Focus on Lupus' and 'Focus on Scleroderma', upon
participants' management of their disease. METHODS: Five people with lupus and
five with scleroderma were invited to take part in individual semi-structured
interviews. Qualitative analysis of transcripts was performed using a framework
approach. Views relating to changes in knowledge and behaviour, increased
empowerment, meeting others and the format and delivery of the programmes were
explored. RESULTS: Analysis of the interviews revealed overall satisfaction with
both programmes, however people with lupus had more positive feelings about their
attendance. Both disease groups considered it valuable to meet others with the
same disease and welcomed the involvement of a patient educator within the
programme planning team. The main difference between the two groups concerned
behaviour change. The lupus group revealed more definite life changes.
Participants unanimously regarded the format of the programme highly and most
were satisfied with the content.
PMID- 17041985
TI - An introduction to medical statistics for health care professionals: describing
and presenting data.
AB - This article is the first in a series of three that will give health care
professionals a sound and helpful introduction to medical statistics. This
article covers three main areas: description of the different types of data
available, appropriate summary measures used to describe different data types,
and methods used to present these data.
PMID- 17041986
TI - The development of a user-led clinical service for newly diagnosed rheumatoid
arthritis patients. An action research study.
AB - OBJECTIVE: To identify the clinical services required to meet the perceived needs
of patients within the first 6-12 months following a diagnosis of rheumatoid
arthritis in an orthopaedic NHS trust. METHODS: An action research methodology
was utilized. Twenty three newly diagnosed patients were asked to complete a
questionnaire focusing on their needs at the time of diagnosis. The content
included reactions to diagnosis, physical and psychological implications and
clinical services that were required. A sub-sample of patients (n = 6)
participated in an interview to explore these issues in more depth. A
questionnaire was also distributed to 14 members of the multidisciplinary team
(MDT) to ascertain their views on the purpose, content, and provision of a
clinical service for newly diagnosed patients. RESULTS: Eighteen patients agreed
to take part (M:F, 9:9, age range 23-74 years, mean age 52.3 years, mean disease
duration from diagnosis 16 weeks). Data from the questionnaires and interviews
led to the following themes being identified: pre-diagnosis anxiety and fear, the
impact of the diagnosis, physical and psychological implications of the
diagnosis, and issues related to control perceptions. There was concordance
between the MDT and the patients regarding impact of the disease and the need for
information. Areas of the service that were identified independently by patients
related to the importance of the period of time pre-diagnosis while awaiting the
hospital appointment, and employment issues. CONCLUSIONS: This study has
identified the impact of RA in the early stages of pre- and post- diagnosis on
physical, psychological and social functioning and has consequently informed
service development.
PMID- 17041987
TI - The Early Rheumatoid Arthritis Network (ERAN).
PMID- 17041988
TI - Long-term observational studies in rheumatoid arthritis: a valuable resource for
clinicians and health professionals.
PMID- 17041989
TI - Clinical and psychological outcomes of patient education in rheumatoid arthritis.
AB - OBJECTIVE: Evidence that patient education improves outcome in self-selected
patients is often based on studies using patients with a mixture of diagnoses
(primarily osteoarthritis) and where the education is delivered in a community
setting. This study explored whether hospital outpatients with rheumatoid
arthritis (RA) who were offered a self-management programme showed a similar
response. METHODS: A randomized controlled trial was undertaken of either
observation or observation plus an educational intervention of five sessions
(12.5 hours) designed to enhance self-management. Pain and self-efficacy for pain
were the primary outcome measures. These and other standardized assessments were
made at 0, 4, 8 and 36 weeks for a variety of psychological and disease states.
Knowledge of RA and its treatment was measured at 0 and 4 weeks using a multiple
choice questionnaire. RESULTS: Sixty-eight of 79 randomized patients provided
adequate data. In those randomized to be offered education, knowledge of RA and
its treatment increased by 18% compared to 9% in controls (p = 0.058). Self
efficacy for pain improved between weeks 0 and 4 by 10.3% (p = 0.015) in those
offered education, and by 14.1% in those who were offered and accepted education
(p = 0.001) but the difference from controls was not maintained after four weeks.
There were no significant differences between groups in pain or in any of the
remaining variables. Most patients reported that the education had been helpful.
CONCLUSIONS: Patients offered education gained knowledge and reported personal
benefit, but only improved in self-efficacy for pain and only for a short time.
RA patients drawn from hospital outpatient clinics and allocated to an
educational intervention may not gain changes in health status as measured by the
instruments employed in this study.
PMID- 17041991
TI - Fife Rheumatic Diseases Unit 10 years on: a personal perspective.
AB - May 2004 marked the 10th anniversary of the Fife Rheumatic Diseases Unit (FRDU)
based at the Sir George Sharp Unit, Cameron Hospital in Fife. This article aims
to share with the reader FRDU's particular model of service delivery, how FRDU,
and the occupational therapy service in particular, has evolved over the past 10
years.
PMID- 17041990
TI - Within-day reliability of temporal-spatial gait parameters associated with
rheumatoid arthritic feet.
AB - OBJECTIVE: To determine whether the GAITRite system can reliably measure temporal
and spatial gait parameters in patients with rheumatoid arthritic feet. METHODS:
Fifty patients diagnosed with rheumatoid arthritis were each measured on two
separate occasions on the same outpatient visit. Temporal and spatial gait
parameter readings were recorded for each of three walks across the GAITRite mat.
Intraclass correlations (2,1) in combination with within-subject standard
deviation were used to quantify within-day reliability. RESULTS: The intraclass
correlation, ranging from 0.75 to 0.87, demonstrated excellent within-day
repeatability for walking speed, cadence, step length and stride length. Good
reliability was reported with cycle time (0.74) and base of support (0.62).
Within-subject standard deviation allows these to be used in a clinical setting.
CONCLUSION: The within-day reliability of temporal and spatial gait parameters in
rheumatoid arthritic patients has been demonstrated in the current study.
However, further investigation of between-day reliability is necessary and would
provide clinicians with reliable data in the objective assessment and any form of
intervention in rheumatoid arthritis patients.
PMID- 17041992
TI - Internet information on rheumatoid arthritis: an evaluation.
AB - OBJECTIVE: To evaluate the quality of internet information, readily accessible by
the public, relating to rheumatoid arthritis and to investigate the relationship
between financial interests of websites and the quality of information provided.
METHODS: Five well-known search engines on the internet were investigated in an
attempt to replicate a search undertaken by a typical patient. The phrase
'rheumatoid arthritis' was used for each search and the first 20 results were
evaluated. Each site was evaluated in terms of 'general website criteria' and
'specific criteria' in relation to rheumatoid arthritis. The websites were scored
out of 30. RESULTS: Fifty-five websites were evaluated. The mean total quality
score was 12.15 (SD = 6.53) and 40 sites (72.7%) scored < 50% of the total marks
available. Information about authorship, ownership and currency were missing in
more than 75% (n = 42) of cases; only 20% (n = 11) of sites gave clear references
to scientific literature; 64% (n = 35) of sites were judged to have a financial
interest and these scored significantly lower total quality scores compared to
the informative sites (p = <0.01). Information about the role of physiotherapy in
the management of rheumatoid arthritis was absent in 70.9% (n = 39). CONCLUSION:
The internet is a poor source of information for rheumatoid arthritis patients.
Quality information is scarce and finding it is time-consuming. Guidelines are
needed to regulate information that is published on the internet and define who
is eligible to publish it. Until then the internet should not be recommended as a
single source of patient information unless professionally endorsed websites are
recommended.
PMID- 17041993
TI - An exploratory survey of the practice of rheumatology nurses addressing the
sexuality of patients with rheumatoid arthritis.
AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic progressive inflammatory
condition primarily affecting the joints. It is characterized by pain, stiffness
and fatigue. Research has demonstrated that the symptoms of RA can negatively
impact on a patient's sexuality and patients would welcome the opportunity to
discuss their sexual needs with a health professional. AIMS: To identify current
perceived practice, skills, and knowledge of rheumatology nurses in addressing
the sexuality of patients with RA. METHODS: A postal questionnaire was sent to
132 rheumatology nurses identified from the British Health Professionals in
Rheumatology Handbook. The questionnaire sought to identify the nurse's role in
the assessment and management of RA patients' sexuality. RESULTS: Seventy six
questionnaires were returned (response rate of 57.5%). Sixty nine respondents
stated that sexuality should be included within the nursing assessment. The main
factors that influenced whether sexuality was discussed was privacy, the level of
knowledge and skills and time. Nurses felt that while contraceptive advice for
patients treated with cytotoxic drugs was discussed in depth, the patient's
sexual relationship was not discussed at all. The majority of respondents (83%)
had never received any training in this area and would undergo training if they
had the opportunity. CONCLUSION: While rheumatology nurses acknowledge the
importance of including sexuality in the care management of patients with RA, in
practice the impact of the condition on a patient's sexuality is only discussed
briefly. Rheumatology nurses have identified the need for further training in
this complex area.
PMID- 17041994
TI - Addressing psychological and social issues of rheumatoid arthritis within the
consultation: a case report.
PMID- 17041995
TI - Adherence with drug therapy in the rheumatic diseases Part one: a review of
adherence rates.
AB - Drug therapy plays a major role in the management of many rheumatic diseases and
is particularly important in rheumatoid arthritis (RA) because of the significant
rates of morbidity and mortality (Pincus, 1995). Understanding of the
pathogenesis of RA has led to the development of new and more effective drugs
(Emery et al., 1999), but the ultimate efficacy of any drug therapy depends upon
the patient's decision to take it. There is widespread agreement that many people
with rheumatic disease do not adhere to their medication regimens (Deyo et al.,
1981; Belcon et al., 1984; Pullar et al., 1988; Hill et al., 2001). Research has
demonstrated that 50% of women taking hormone replacement therapy for the
prevention of osteoporosis discontinue treatment after a year (Fordham, 2000) and
similar rates of discontinuation are found in other chronic diseases (Haynes et
al., 1996, 2000). This is bewildering as, in asymptomatic illnesses such as
hypertension and diabetes, the expectation is that levels of adherence would be
lower than in diseases where pain and stiffness are present. The picture becomes
even more confusing when we consider the findings from a recent multi-country
study of RA, which found no association between adherence and disease severity,
nor with the treatment prescribed (Viller et al., 1999). In chronic disease poor
adherence is commonplace. The World Health Organization (WHO) recognizes this and
has recently stated that 'poor adherence to treatment of chronic diseases is a
worldwide problem of striking magnitude' and cites adherence to long-term therapy
for chronic illnesses in developed countries averaging just 50% (WHO, 2003). The
first part of this two part review focuses on adherence with drug therapy, and
the second part discusses different methods of measuring it.
PMID- 17041996
TI - How people with rheumatoid arthritis perceive leisure activities: a qualitative
study.
AB - OBJECTIVE: To explore how people with rheumatoid arthritis (RA) perceive leisure
activities. METHOD: A phenomenographic approach using semi-structured interviews
to explore the impact of RA on leisure pursuits was used. RESULTS: Three
descriptive categories containing 11 conceptions emerged: (1) Experiencing
constraints included four conceptions: seeing limitations, needing time, finding
balance, being dependent. (2) Experiencing coherence included four conceptions:
accepting feelings participating in a social context, being active, having
insight. (3) Finding solutions included three conceptions: choosing, planning,
and adapting. CONCLUSIONS: This study emphasizes the limited choices and problems
people with RA had participating in leisure activities, as well as its impact on
self-esteem.
PMID- 17041997
TI - Static orthoses in the prevention of hand dysfunction in rheumatoid arthritis: a
review of the literature.
AB - Static orthoses are recommended for individuals who have early rheumatoid
arthritis (Scottish Intercollegiate Guidelines Network, 2002; College of
Occupational Therapists, 2003). These orthoses aim to rest and immobilize
weakened joint structures and decrease local inflammation (Janssen et al., 1990;
Nicholas et al., 1982); correctly position joints (Nordenskiold, 1990; Ouellette,
1991); minimize joint contractures (McClure et al., 1994); increase joint
stability (Kjeken et al., 1995); relieve pain (Feinberg, 1992; Callinan and
Mathiowetz, 1996; Kjeken et al., 1995) and improve function (Janssen et al.,
1990; Pagnotta et al., 1998; Nordenskiold, 1990). Wrist and hand orthoses have
been routinely prescribed for individuals with rheumatoid arthritis (RA) for the
last 30 years with limited evidence that they are effective in achieving their
purported aims. This article reviews the possible deterioration in hand structure
that can occur in RA and discusses the theoretical basis for the application of
static orthoses in RA. The evidence for the effectiveness of four commonly used
static orthoses is then examined.
PMID- 17041998
TI - An introduction to medical statistics for health care professionals: Hypothesis
tests and estimation.
AB - This article is the second in a series of three that will give health care
professionals (HCPs) a sound introduction to medical statistics (Thomas, 2004).
The objective of research is to find out about the population at large. However,
it is generally not possible to study the whole of the population and research
questions are addressed in an appropriate study sample. The next crucial step is
then to use the information from the sample of individuals to make statements
about the wider population of like individuals. This procedure of drawing
conclusions about the population, based on study data, is known as inferential
statistics. The findings from the study give us the best estimate of what is true
for the relevant population, given the sample is representative of the
population. It is important to consider how accurate this best estimate is, based
on a single sample, when compared to the unknown population figure. Any
difference between the observed sample result and the population characteristic
is termed the sampling error. This article will cover the two main forms of
statistical inference (hypothesis tests and estimation) along with issues that
need to be addressed when considering the implications of the study results.
PMID- 17041999
TI - Patients as teachers: a new approach to patient involvement.
AB - Patients as Teachers is an approach to patient involvement which involves
bringing together a key sub-group for a speciality with a facilitator to focus on
particular aspects of the service. This approach was used by the rheumatology
team in Bradford to elicit feedback from South Asian women for whom English is
not the first language. The focus groups generated constructive feedback about
issues relating to, the hospital environment, information giving and service
provision. This was fed back to clinicians at an educational meeting attended by
lay representatives, and agreed actions were determined. Progress made on the
recommendations was evaluated at six months.
PMID- 17042001
TI - The updated BSR guidelines for anti-TNF in adults with RA: what has changed and
why?
AB - In 2001 the British Society for Rheumatology (BSR) published guidelines for
prescribing TNF-alphablockers in adults with rheumatoid arthritis (RA). In an
unusual move, the National Institute of Clinical Excellence (NICE) accepted the
BSR guidelines and published them unchanged and included them in their own
Technology Appraisal (National Institute of Clinical Excellence, 2002). The field
of anti-TNF in RA is rapidly changing, and the BSR Standards, Guidelines and
Audit Working Group decided in 2004 to update the guidelines. These were
published in February 2005 (Ledingham and Deighton, 2005). This article
summarizes the key changes, and attempts to justify them, using further data that
has emerged since the updated guidelines were produced, and audit data from the
Derby Rheumatology department.
PMID- 17042003
TI - Adherence with drug therapy in the rheumatic diseases Part two: measuring and
improving adherence.
AB - Part one of this review highlighted the problem of high rates of non-adherence
with drug therapy in the rheumatic diseases. Part two addresses the problem of
assessing adherence to drug therapy, focuses on factors affecting medication
taking and discusses interventions that can help to improved adherence.
PMID- 17042002
TI - Outcomes generated by patients with rheumatoid arthritis: how important are they?
AB - BACKGROUND: It has been shown previously that patients with rheumatoid arthritis
(RA) can generate a wide range of outcomes that they consider important in
treatment. It is not known if these outcomes are generally important in the wider
RA patient community. OBJECTIVES: (1) To examine whether recent patient-generated
outcomes are generalizable within a wider RA population; (2) to assess the
relative importance of each outcome; and(3) to explore whether any important
outcomes have been omitted. METHODS: A questionnaire, listing 23 outcomes
previously generated by RA patients, was distributed through three rheumatology
centres in the UK. Patients gave an importance score to each outcome (0-3),
selected their top three most important outcomes, and then listed any outcomes of
personal importance that were missing. RESULTS: 323 questionnaires were returned
(65%). All outcomes were deemed important. Independence, pain, and mobility were
most frequently selected by patients in their top three outcomes but were not
chosen by 61-66% of patients. The next most commonly chosen outcomes related to
feeling well and fatigue. Factor analysis revealed six reasonably distinct
groupings: general well-being (11.9% explained variance), day-to-day
functioning(10.6%), emotional and psychological well-being (10.6%), social role
and confidence (10%), physical symptoms (9.5%) and medication issues (7.9%).
CONCLUSION: Outcomes generated by patients as important in RA, are generalizable
and inclusive. The most important (independence, pain and mobility) are routinely
treated and measured. The next most important (feeling well, fatigue) are
infrequently addressed and deserve urgent consideration for measurement,
treatment and research.
PMID- 17042004
TI - Perception of tactile massage as a complement to other forms of pain relief in
rheumatic disease.
AB - OBJECTIVE: To investigate how patients with rheumatic disease perceive tactile
massage as a complement to other pain alleviation methods. METHODS: A
phenomenographic approach with semi-structured interviews was employed on a
strategic sample of 14 patients with various rheumatic diseases, both
inflammatory and non-inflammatory, who had been admitted to Spenshult Rheumatic
Hospital. RESULTS: Three descriptive categories with a total of nine conceptions
emerged. The descriptive categories were: experiencing alleviation, experiencing
trust, and gaining insight. Experiencing alleviation described how patients
experience relaxation, pleasure and respite. Experiencing trust described how
patients experience a sense of security, confirmation and inner peace. Gaining
insight described how patients get to know themselves, see possibilities, and
experience wholeness. CONCLUSIONS: When caring for patients who have a chronic
illness involving considerable changes to their lives, it is important for health
professionals not only to be aware of their physical needs but also to take
account of the whole person. This study demonstrates the importance of offering
patients a complement to conventional treatment. Tactile massage is a method that
promotes a holistic view of patients with chronic pain as well as allowing them
to find a new focus in terms of the disease and how they cope with it in their
daily lives.
PMID- 17042005
TI - Providing specialist clinical skills in soft tissue and intra-articular injection
through a postgraduate masters module.
AB - Current philosophy and policy changes in the National Health Service are
encouraging healthcare practitioners to extend their clinical skills to create a
more patient-centred approach thus allowing patients to be seen in a timely and
more appropriate manner. This often requires further development of the
practitioners' skills and knowledge. One approach to achieve this is through
collaboration between employers and educational providers to ensure that
educational experience is not only evidence based but also responsive to the
needs of the current and future workforce. A postgraduate module was developed to
raise critical and evaluative skills, as well as the technical skills of
practitioners using injections in the management of joint and soft tissue
pathology, while developing a professional responsibility towards injection
practice. The module emphasized learning though experience by contextualizing the
theoretical aspects of the module and by its student centred assessments. Further
strengths of this module are that it has utilized academic and clinical expertise
and knowledge to enable clinicians to gain additional skills and the
multidisciplinary approach engendered good working practice Overall the module
was evaluated positively by both tutors and students and not only met its aims
but also addressed the current professional and policy issues around continuing
professional development.
PMID- 17042006
TI - Prescribing and injecting: the expanding role of the rheumatology nurse.
PMID- 17042007
TI - How effective is physiotherapy in the treatment of complex regional pain syndrome
type I? A review of the literature.
AB - Complex regional pain syndrome (CRPS) is a debilitating pain disorder for which
patients commonly receive physiotherapy. The objective of this literature review
is to assess how effective physiotherapy is in the management of adult and
childhood CRPS type I. An electronic literature search was performed of the
databases AMED, Cinahl, Embase, Ovid Medline, Pubmed, PEDro and PsycINFO, from
their inception to November 2004. Human subjects clinical trials, written in
English, which could assist in answering the research question were included.
Twenty-five (of 748) papers met the inclusion criteria and were reviewed. The
review suggests that exercise, motor imagery and mirror feedback exercises,
relaxation techniques, acupuncture, electroacupuncture, transcutaneous nerve
stimulation and combined treatment programmes may help in the treatment of CRPS
type I. However, since numerous methodological weaknesses (e.g. small sample
sizes, not employing control groups, not evaluating findings against statistical
tests) littered the limited literature, it was not possible to determine the
effectiveness of individual treatments. Recommendations are made to develop the
evidence base.
PMID- 17042008
TI - An introduction to medical statistics for health care professionals: basic
statistical tests.
AB - This article, the third and final article in the series, aims to give health care
professionals (HCPs) a sound and helpful introduction to medical statistics
(Thomas, 2004, 2005). A brief summary of the content of the previous articles is
given in Table 1. The current article will cover the area of basic statistical
tests with the aim of guiding HCPs to the correct test for a particular research
question and dataset. The article will not go into great depth of the formal
methods of calculation required for all the tests covered but I would suggest
that the reader refer to standard textbooks (Jordan et al., 1998; Swinscow, 1998;
Altman, 1994; Bland, 2000), the help sections of statistical packages (SPSS or
Stata), or consult a statistician. For ease of reference within the article the
tests have been grouped by the data type, i.e. numerical or categorical. Further
separation within each data type has been carried out depending on the number of
groups being compared, whether the groups are independent, the size of the
sample, and, in the case of numerical data, the distribution of the variable. For
quick reference, two other tables are also presented which summarize which
analysis methods should be used in each situation.
PMID- 17042009
TI - Patients' perceptions of drug dispensing in a rheumatological in-patient unit.
AB - INTRODUCTION: The dispensing of drugs in medical care systems is, in most
countries, strictly regulated, and nurses are responsible for distributing drugs
to in-patients. AIM: To describe the perceptions of patients with rheumatic
diseases regarding traditional drug dispensing during in-patient care and
rehabilitation in a specialized rheumatological care unit. METHOD: Twenty in
patients who stayed in the Spenshult Hospital unit for 3-4 weeks and who were on
continuous medication were chosen for the study. The phenomenographic approach
was used for the collection and analysis of data. FINDINGS: Three descriptive
categories emerged - Relief, Active Participation and Dependence. These
descriptive categories comprised: three perceptions for Relief (to experience
security, to be 'served', to dare to bother), two for Active Participation (to
rely on one's own ability, to search for knowledge) and two for Dependence (lack
of independence, lack of information). CONCLUSION: The patients experienced
relief due to the nurse assuming responsibility for the medication and its
dispensation. Patients expressed a wish to be more active in the management of
their medication, as they trusted their own ability. The patients articulated
that they were dependent on the nurse to give them the correct medication and
they also asked for more information about their medication.
PMID- 17042010
TI - Paracetamol use in musculoskeletal pain: an audit of use and patient perceptions
of paracetamol as an effective analgesic.
AB - Musculoskeletal pain is a complex problem with often very detrimental
consequences which affects a high proportion of the general population. Health
care professionals, when prescribing for musculoskeletal pain, often overlook
simple analgesia. Patient perceptions of analgesia may vary to those of health
care professionals, and in part affect the use of simple analgesia for
musculoskeletal pain. This paper describes an audit of paracetamol use and
patient perceptions of paracetamol as an effective analgesic agent, in 113
patients attending a musculoskeletal pain outpatient clinic in a university
teaching hospital. The audit has helped prompt the development of a multi
disciplinary strategy to achieve optimum management.
PMID- 17042011
TI - An evaluation of nurse-led rheumatology telephone clinics.
AB - AIMS AND OBJECTIVES: The aim of the study was to examine the impact on waiting
times and patient satisfaction of nurse-led rheumatology telephone clinics.
METHODS: Patients awaiting outpatient review were contacted by the rheumatology
clerk and offered a nurse-led rheumatology telephone appointment. Those who
accepted were given a date and time for the appointment. A telephone consultation
proforma was used to structure the call and to organize appropriate
investigations/action. A questionnaire was mailed to the 68 patients reviewed
during the first month of the telephone clinics to assess satisfaction. Status
forms were also completed to record further action. RESULTS: Of the 68 patients
surveyed 73% completed and returned the questionnaire. Overall 72% were happy
with the telephone consultation and would be happy to use the service again.
Waiting times were reduced by two months as a total of 169 patients were reviewed
during the April to August period. CONCLUSION: Nurse-led telephone consultation,
as part of chronic disease management, can be extremely beneficial for all
rheumatology patients as a high level of satisfaction was achieved. In addition
telephone consultations have helped to reduce the follow-up waiting times within
the department by two months. This audit shows that telephone appointments
conducted by an experienced nurse using an assessment proforma can be
incorporated into routine follow-up care.
PMID- 17042012
TI - High disease activity scores predict the need for additional health services in
patients over 60 with rheumatoid arthritis.
AB - OBJECTIVE: To determine whether we meet perceived need, in terms of appropriate
supportive health services (physiotherapy, occupational therapy, chiropody and
footwear, surgery, education and information), of patients aged 60 years and over
with rheumatoid arthritis (RA). DESIGN: A cross-sectional survey. PARTICIPANTS:
123 patients attending rheumatology outpatient clinics. RESULTS: The response
rate was 82% (99/123). Of the respondents 78% had one or more perceived needs.
Respondents were more likely to express a need for chiropody or footwear (46%),
education about RA (29%), or physiotherapy (22%) than for occupational therapy
(7%) or surgery (6%). Further analysis compared this group with the 'non-needy'
group. There was a correlation between high disease activity scores and high
anxiety scores and greater perceived need for additional health services.
CONCLUSION: There was significant unmet demand for chiropody and footwear,
education about RA, physiotherapy, occupational therapy and surgery. It is
possible that strategies to reduce anxiety and improve control of active
inflammatory disease may reduce demand for supportive services in certain
patients.
PMID- 17042013
TI - Measuring sensation in the feet of patients with rheumatoid arthritis.
AB - OBJECTIVES: (1) To determine the test-retest reliability of monofilaments pressed
against the skin as a method of assessing sensation in the feet of patients with
rheumatoid arthritis (RA) and in controls using two grades of monofilaments; (2)
to determine the stability of findings over 6 weeks; and (3) to calculate initial
estimates of frequency of loss of sensation and to investigate its association
with disease status. METHOD: Clinical examination of the feet was undertaken in
51 patients with RA and 20 normal controls. Six sites on each foot were tested
twice with both 10 g and 3 g research grade monofilaments and this was repeated
after 6 weeks. Disease status was measured using the Disease Activity Score, the
Health Assessment Questionnaire, visual analogue scales of pain, and the acute
phase response using erythrocyte sedimentation rate and plasma viscosity.
RESULTS: Reproducibility was high for 3 g (kappa=0.73) and 10 g (kappa=0.75)
monofilaments. The best balance between sensitivity (58.8%) and specificity
(87.5%) for distinguishing the feet of patients from the feet of controls was
using the 3 g filament and defining reduced protective sensation as being
sensitive to less than 11 of 12 applications. Using this definition, the
prevalence of reduced protective sensation is 59% in the patient group and 12.5%
in the feet of controls. There was some variation in sensation over 6 weeks in
the patient group, but this was not related to measures of clinical status.
CONCLUSION: The use of monofilaments in assessing sensation levels in the RA foot
is repeatable and reproducible over a six-week period and requires only a short
time to perform. The frequency of reduced sensation in the feet of patients with
RA was greater than previously reported. Future studies should assess
relationships with disease duration and inflammatory status.
PMID- 17042014
TI - Rheumatology telephone helplines: patient and health professionals' requirements.
AB - OBJECTIVES: The aim of this study was to ascertain patients' and health
professionals' requirements from a rheumatology helpline and how such a service
should be delivered. METHODS: Self-completed questionnaires were administered to
both users of rheumatology helplines, patients and health professionals (HPs),
and providers of rheumatology services at five UK NHS trusts. Additional data
were sought from experts in the field. Information was elicited on access to the
service, preferred waiting time for response to a call, acceptability of an
answerphone and choice of HP responding. Quantitative data were analysed using
percentages and Chi-squared tests. Open questions were analysed as free text
responses, and organized into clusters of themes. RESULTS: A total of 607
questionnaires were returned, 523 from users (411 patients, 112 health
professionals) and 84 from providers. There were no significant differences
across the five Trusts. The top six reasons for patients contacting the helpline
were: advice on changes in condition, drug information, understanding symptoms,
blood results, information on diagnosis, and appointment queries. All groups
recommended a return call on the same day and were happy to leave an answerphone
message. HP users requested additional access via e-mail and fax. Rheumatology
practitioners were deemed the most appropriate personnel to staff a helpline.
CONCLUSIONS: The findings of this study have contributed a valuable insight into
the essential components of a rheumatology helpline service from a user and
provider perspective. These data will add to existing recommendations for the
management of a rheumatology helpline service and ultimately contribute to a
proposal for national guidelines.
PMID- 17042015
TI - Leadership in health care.
PMID- 17042016
TI - Multiprofessional education for allied health professionals in rheumatology:
breaking down traditional barriers.
PMID- 17042017
TI - Patient-reported outcome: Measuring what matters or just another paper exercise?
PMID- 17042018
TI - Is the drive to manage long-term conditions in the community compatible with
improving standards of care for those with inflammatory arthritis?
AB - At the same time as the Government is pushing ahead with its agenda to manage
long-term conditions in the community, standards of care have been published by
the Arthritis and Musculoskeletal Alliance (ARMA) in an attempt to improve and
standardize the care of people with inflammatory arthritis. This raises the
question of whether the needs and preferences of people with arthritis can be
adequately met in a primary care setting. This paper looks at the evidence so far
and discusses the possibilities for achieving ARMA's standards if arthritis care
is managed in the community.
PMID- 17042019
TI - Evaluation of the Bristol Royal Infirmary physiotherapy programme for the
management of patients with osteoarthritis of the knee.
AB - The aim of this paper is to investigate whether comparable outcomes can be
achieved when research evidence is translated into clinical practice in the
management of osteoarthritis (OA) of the knee. An evidence-based physiotherapy
programme for the management of OA of the knee was established at the Bristol
Royal Infirmary (BRI). It incorporated both group education and exercise into a
six week course. Outcomes from the programme were measured using the WOMAC self
evaluated questionnaire which is sub-divided into pain, stiffness and function
sections with an additional visual analogue scale (VAS) for pain in each knee.
Outcomes from the BRI programme were compared with those reported in four papers
which used similar interventions and evaluation tools. A reduction in pain (VAS)
of 43% was demonstrated following this programme compared with a mean reduction
of 16% reported in the other programmes investigated. It is concluded that
favourable outcomes for patients can be achieved by implementing evidence into
practice, e.g. in the BRI knee programme.
PMID- 17042020
TI - Rheumatology nurse practitioners' perceptions of their role.
AB - OBJECTIVES: To identify the current practices of rheumatology nurse practitioners
and ascertain their perceptions of how their role could be enhanced. METHOD: A
cross-sectional questionnaire study of currently employed nurse practitioners in
rheumatology in the United Kingdom (UK) was undertaken. RESULTS: 200
questionnaires were distributed and 118 nurses responded. Ninety-five respondents
met the inclusion criteria for undertaking an advanced nursing role. Typical
conditions dealt with included: rheumatoid arthritis (96.8%); psoriatic arthritis
(95.8%); osteoarthritis (63.2%); ankylosing spondylitis (62.8%); systemic lupus
erythematosus (51.6%); and scleroderma (34.7%). Drug monitoring, education,
counselling of patients and arranging basic investigations were routinely
performed by more than 80% of respondents. A smaller proportion performed an
extended role that included dealing with referrals, research and audit, the
administration of intra-articular injections, and admission of patients. Specific
attributes identified as being necessary for competence were: knowledge and
understanding of rheumatic diseases (48.4%); drug therapy (33.7%); good
communication skills (35.8%); understanding of the roles of the team (27.4%);
working effectively (23.2%) as part of a multidisciplinary team; assessment of
patients by physical examination (28.4%); teaching (26.3%), research (17.9%);
organizational skills (14.7%); and the interpretation of investigations (9.5%).
Factors that could enhance their role included: attendance at postgraduate
courses (30.5%); obtaining further qualifications (13.7%); active participation
in the delivery of medical education (41.1%); training in practical procedures
(31.6%); protected time and resources for audit and research (11.6%); formal
training in counselling (11.6%); and implementation of nurse prescribing (10.5%).
CONCLUSION: Nurse practitioners already have a wide remit and play an invaluable
part in the delivery of modern rheumatology services. An extended role could
improve patient care and enhance nursing career pathways in rheumatology.
PMID- 17042021
TI - Why do patients with rheumatoid arthritis use complementary therapies?
AB - OBJECTIVES: (1) to develop an understanding as to how the use of complementary
therapy (CT) affects a patient's perspective of health and well-being, (2) to
offer the rheumatology professional insight and understanding as to why a patient
chooses to use a CT, and (3) to raise awareness as to the forms of CT most
commonly used by patients with rheumatoid arthritis. METHODS: This qualitative
study was based on phenomenological principles applied through focused inquiry to
develop an understanding of the lived experience of the study participants. The
inclusion criteria of an established diagnosis of rheumatoid arthritis and known
use of CT were applied to a convenience sample of patients attending a
rheumatology outpatient department clinic on two consecutive days. Of the 15
eligible patients identified, five were randomly selected for inclusion in the
study. Narrative data were collected through analysis of transcripts taken from
audiotape recordings of unstructured interviews with study participants. A manual
indexing system was used to develop four significant categorisation themes to
reflect the findings: (1) incentives to use CT, (2) perceived benefits of CT use,
(3) the choice of CT used, and (4) perceived disadvantages and risks of CT use.
RESULTS: Incentives to use CT included dissatisfaction with conventional
treatment, often in the form of side effects, and drug ineffectiveness. Social
factors, such as loss of employment and social activities, were also indicated,
as were psychological changes in the form of depression, hopelessness and fear.
Perceived benefits were categorised as either physical or psychological with
associated aspects of choice and control viewed as important elements of personal
empowerment. The choice of CT used fell into three categories; physical,
spiritual and herbal. The most commonly used of these were herbal remedies and
supplements, closely followed by aromatherapy massage. Disadvantages and risks
were identified as physical (pain and discomfort), psychological (fear and
uncertainty), and/or material (cost). CONCLUSIONS: This study suggests that
regular use of CT by patients with rheumatoid arthritis offers holistic benefits.
Compared to conventional treatments, CT is seen to have advantages in terms of a
lower incidence of adverse reactions, greater patient choice, psychological
comfort and an increased quality of the patient/therapist relationship. The use
of CT by patients with rheumatoid arthritis indicates a need for evidence-based
information about its use and safety in order to direct practice within a
rheumatology department.
PMID- 17042022
TI - Accelerating teamwork: A personal reflection.
PMID- 17042023
TI - Putting caring into research - the CARE conferences.
PMID- 17042024
TI - Influences that drive clinical decision-making among rheumatology nurses. Part 1:
literature review.
AB - Decisions nurses make while providing patient care to their client group will
impact on the patient's immediate and long-term outcomes and will also impact on
service provision. Although many studies have focused on the clinical decision
making process itself within general nursing areas, little has been published as
to what factors influence decisions in rheumatology nursing at the clinical
level. Initial review of the literature suggested the following themes could
influence decision-making: clinical decision-making, intuition, evidence-based
practice, experiential learning, knowing the patient, skilled knowledge and
rheumatology nursing. This article examines the literature surrounding clinical
decision-making which may influence decision-making within rheumatology nursing
practice.
PMID- 17042025
TI - Physiotherapy rehabilitation in patients with massive, irreparable rotator cuff
tears.
AB - BACKGROUND: Massive rotator cuff tears provide a challenge for effective
rehabilitation. Work has been ongoing at Torbay Hospital, Devon since 2000 to
develop an exercise programme for the management of this patient group. This
programme has been evaluated in a pilot study and a further randomised controlled
trial is currently taking place which will enable us to estimate the treatment
effect. This paper discusses the background to the development of the
rehabilitation programme, the programme itself and the results of the pilot
study. The pilot study was an evaluation of the rehabilitation programme.
OBJECTIVES: This study examined the effectiveness of a physiotherapy regime for
the treatment of patients with massive rotator cuff tears. METHODS: Patients
identified through primary and secondary care referrals to physiotherapy with a
clinical diagnosis of a massive rotator cuff tear underwent an ultrasound scan to
confirm the diagnosis. A massive cuff tear was one where the leading edge of the
tear had retracted past the glenoid margin. The clinical diagnosis was based on
the presence of some or all of the following signs: positive humeral thrust on
elevation, gross weakness and wasting of supraspinatus and infraspinatus,
infraspinatus lag and rupture of the long head of biceps. Eligible patients were
invited to take part in the study and informed consent was obtained. The baseline
assessment was carried out and then the patient undertook the treatment
programme. Outcome measures were reassessed 12 weeks from the baseline
assessment. DESIGN: A cohort study of 10 patients evaluating the change from
baseline to twelve weeks in the shoulder function of patients undergoing a
programme of anterior deltoid strengthening and functional rehabilitation. The
outcome measures used were the Oxford Shoulder Disability Questionnaire (OSDQ)
and SF36. The OSDQ is validated for use with the UK population and has 12
questions with 5 point responses. The lowest (best) score is 12 and the highest
(worse) score is 60. RESULTS: Scores on the OSDQ improved with all patients. The
mean improvement was 9 (range 3 to 16, standard deviation 10.3). The SF36 showed
an improvement in the pain scores for all patients (mean 22 points) and an
overall improvement of 10 points for the sections on role limitation due to
physical health. There was an overall decline in perceived general health (9
points) and in role limitation due to emotional health (23 points). CONCLUSIONS:
As all 10 patients showed improved scores on the OSDQ, in spite of the long
standing nature of many of their shoulder problems, this rehabilitation programme
was shown to improve shoulder function in this group of patients. The variation
shown in the quality of life scores reflects the age group of this cohort who had
a mean age of 75.5 years. All patients deemed their pain and function to have
improved over the three-month period.
PMID- 17042026
TI - Personal impact of disability in osteoarthritis: patient, professional and public
values.
AB - BACKGROUND: Osteoarthritis (OA) is a leading cause of disability. Numerous tools
are available to assess this, but they fail to place a patient value upon
disability. In rheumatoid arthritis, research has shown patients have different
importance values for similar disabilities, and these individual values can be
used to weight disability levels, creating a measure of personal impact.
OBJECTIVES: Firstly, to determine if the Health Assessment Questionnaire (HAQ)
can be used as the basis for an importance value scale by assessing if it
includes activities considered important by OA patients. Secondly, to determine
if the weights used for the value scale should be based on population, healthcare
professional or patient values. METHOD: Twenty-five OA patients, 25 healthy
controls and 25 healthcare professionals rated the importance of the items on the
HAQ and shortened Modified HAQ (MHAQ). Prior to completing the HAQ, patients
generated a list of activities that were important to them. RESULT: The HAQ
contained 69% of items that patients considered important. No items were
consistently deemed unimportant by patients. There was low agreement within and
between groups about the importance of the items on the HAQ and MHAQ. CONCLUSION:
The HAQ is a suitable basis for a value scale for an OA disability impact score.
Importance values for function differed for patients, healthcare professionals
and the general population; therefore individual patient weightings need to be
used. Further work is under way to validate a measure of the personal impact of
disability in patients with lower limb OA.
PMID- 17042027
TI - Exploring the perceived role and impact of the nurse consultant.
AB - BACKGROUND: Nurse consultant roles were introduced in 1999 with defined role
criteria including expert practice, research, education and leadership. The
primary objective of the role is to develop nurses and nursing to provide
effective patient outcomes. In 2000 the first nurse consultant in rheumatology
was appointed to establish a co-ordinated service for the management of patients
with chronic musculoskeletal pain. There are now ten nurse consultants within
rheumatology yet little is known of their role or impact. AIM: The aim of the
study was to identify the perceived role and impact of one nurse consultant (NC)
in rheumatology within the context of being a practitioner-researcher. METHOD:
Seven peers of the NC and five patients cared for by the NC participated in a
semi-structured interview to identify their perceptions regarding the role of the
NC within the rheumatology service. RESULTS: The following themes were identified
from the interviews: (1) development of a new model of care for patients with
chronic musculoskeletal pain; (2) holistic person-centred care experienced and
valued by the patient; (3) leadership and education; and (4) feeling cared for.
CONCLUSION: The NC role had impacted on service development and culture in the
instigation of a chronic musculoskeletal pain service and leadership and
education activities. Patients experienced the holistic nature of the role.
PMID- 17042028
TI - The new British Society for Rheumatology disease modifying anti-rheumatic drugs
guidelines.
PMID- 17042029
TI - Competency frameworks and the changing workforce.
PMID- 17042030
TI - Bats as a continuing source of emerging infections in humans.
AB - Amongst the 60 viral species reported to be associated with bats, 59 are RNA
viruses, which are potentially important in the generation of emerging and re
emerging infections in humans. The prime examples of these are the lyssaviruses
and Henipavirus. The transmission of Nipah, Hendra and perhaps SARS coronavirus
and Ebola virus to humans may involve intermediate amplification hosts such as
pigs, horses, civets and primates, respectively. Understanding of the natural
reservoir or introductory host, the amplifying host, the epidemic centre and at
risk human populations are crucial in the control of emerging zoonosis. The
association between the bat coronaviruses and certain lyssaviruses with
particular bat species implies co-evolution between specific viruses and bat
hosts. Cross-infection between the huge number of bat species may generate new
viruses which are able to jump the trans-mammalian species barrier more
efficiently. The currently known viruses that have been found in bats are
reviewed and the risks of transmission to humans are highlighted. Certain
families of bats including the Pteropodidae, Molossidae, Phyllostomidae, and
Vespertilionidae are most frequently associated with known human pathogens. A
systematic survey of bats is warranted to better understand the ecology of these
viruses.
PMID- 17042031
TI - Prenatal diagnosis of trisomy 21 without the Down syndrome phenotype.
AB - OBJECTIVE: To report a patient with the prenatal diagnosis of trisomy 21 without
the clinical Down syndrome (DS) phenotype secondary to the absence of the Down
syndrome chromosomal region (DSCR) in a derivative chromosome 21. CASE REPORT AND
METHODS: A newborn patient with prenatal diagnosis of duodenal atresia.
Cytogenetic studies revealed a regular trisomy 21. At birth, she did not present
the clinical features of DS. FISH analysis was performed in the patient with the
LSI spectrum probe for the DSCR and in the mother with FISH multicolor analysis
using painting probes for chromosomes 20 and 21. RESULTS: FISH analysis in the
patient showed two hybridization signals suggesting that the third chromosome 21
did not have the DSCR region explaining the absence of the DS phenotype. FISH
multicolor analysis in the mother showed three hybridization signals for
chromosomes 20 and 21, concluding a maternal karyotype,
46,XX,t(20;21)(p11.2;q22.1). CONCLUSIONS: The patient was found to have a
derivative chromosome 21 secondary to a nondisjunction error in meiosis II
without the DS critical region and the phenotype was mostly secondary to the
combination of the two partial trisomies.
PMID- 17042032
TI - Structural elucidation of nitro-substituted five-membered aromatic heterocycles
utilizing GIAO DFT calculations.
AB - The GIAO (Gauge Including Atomic Orbitals) DFT (Density Functional Theory) method
is applied at the B3LYP/6-31+G(d,p)//B3LYP/6-31+G(d), B3LYP/6
311++G(d,p)//B3LYP/6-31+G(d), B3LYP/6-311+G (2d,p)//B3LYP/6-31+G(d) and B3LYP/6
311++G(d,p)//B3LYP/6-311++G(d,p) levels of theory for the calculation of proton
and carbon chemicals shifts and coupling constants for 25 nitro-substituted five
membered heterocycles. Difference (1D NOE) spectra in combination with long-range
gHMBC experiments were used as tools for the structural elucidation of nitro
substituted five-membered heterocycles. The assigned NMR data (chemical shifts
and coupling constants) for all compounds were found to be in good agreement with
theoretical calculations using the GIAO DFT method. The magnitudes of one-bond
(1JCH) and long-range (nJCH, n>1) coupling constants were utilized for
unambiguous differentiation between regioisomers of nitro-substituted five
membered heterocycles.
PMID- 17042033
TI - Gene duplications in 21-hydroxylase deficiency: the importance of accurate
molecular diagnosis in carrier detection and prenatal diagnosis.
AB - BACKGROUND: The detection of 21-OH deficiency (21OHD) carriers in the general
population requires that misinterpretations of apparently severe mutations in
alleles carrying duplicated genes be avoided. Prenatal treatment prevents
virilization in female fetuses and genetic counseling may be offered to couples
in which one partner is either a patient or a carrier. This paper proposes a
semiquantitative PCR method involving primer extension that distinguishes the
severe point mutation Q318X in single gene copy alleles from the
normal/nondeficient variant in gene-duplicated alleles. SAMPLES AND METHODS: DNA
from 65 individuals carrying Q318X variants, that of 85 partners of 21OHD
carriers or patients, and one fetal sample (as well as the DNA of his family)
were analyzed. 21OHD alleles were studied by gene-specific PCR/allele-specific
oligonucleotides hybridization for common mutations, Southern analysis,
complementary direct sequencing and microsatellite typing. Primer extension
analysis of the Q318X variants using fluorescent dideoxynucleotides was performed
on CYP21A2 gene-specific PCR-amplified DNA samples from controls, patients,
potential carriers and prenatal samples. RESULTS: Different fluorescence patterns
were seen for the severe mutation (single gene copy) and the nondeficient (gene
duplicated) alleles carrying Q318X. The normal/mutant fluorescence peak (N/M)
ratio was < 1 in all heterozygous carriers (mean 0.83; min. 0.70; max. 0.95). In
all normal individuals carrying the gene-duplicated Q318X normal variant, the N/M
ratio was > 1 (mean 1.69; min. 1.44; max. 2.02). CONCLUSION: The proposed method
discriminated between the severe Q318X mutation and the normal Q318X variant in
gene duplication, and could be a useful complementary tool in prenatal diagnosis
and carrier detection.
PMID- 17042034
TI - The "Consecutive Combined Test"--using double test from week 8 + 0 and nuchal
translucency scan, for first trimester screening for Down syndrome.
AB - OBJECTIVE: To test the performance of the "Consecutive Combined Test", applied on
a high-risk population. The classic "Combined Test" (Double test (DT) and Nuchal
Translucency (NT) measurement on the same day at app. week 12) gives detection
rates (DR) for Down syndrome (DS) of 80-90% for false positive rates (FPR) of 5%.
In affected pregnancies, however, the low PAPP-A level is more pronounced, the
earlier in pregnancy. Thus, we hypothesized that the Double Test could be taken
as early as from week 8 + 0, without compromising the excellent performance of
the Combined Test. This "Consecutive Combined Test" allows for a centralised
laboratory function. METHODS: Inclusion criteria were maternal age > 35 years
(80%) or a family history (20%). Double test was taken at a median gestational
age (GA) = 10 weeks. NT was measured at GA = 11 + 0 - 13 + 6. A combined risk
estimate of > 1:400 at birth was used as cut-off. RESULTS: 881 had the full test.
Screen positive = 34. CVS with aneuploidy = 11 (6 trisomy-21, 5 others). FPR =
3.2%. Positive Predictive Value (PPV) = 17.6% for T-21. CONCLUSION: The
"Consecutive Combined Test" applied on a high-risk population seems to be highly
efficient with a remarkably high PPV.
PMID- 17042036
TI - Silica-immobilized chromium colloids for cyclohexane autoxidation.
PMID- 17042035
TI - Cervical length in women in preterm labor with intact membranes: relationship to
intra-amniotic inflammation/microbial invasion, cervical inflammation and preterm
delivery.
AB - OBJECTIVE: Intra-amniotic infection, diagnosed by microbial invasion of the
amniotic cavity (MIAC) and/or the presence of intra-amniotic inflammation (IAI),
is related to adverse perinatal outcome in women with preterm labor. Due to the
subclinical nature of IAI, a correct diagnosis depends on amniocentesis, which is
an invasive method not performed as a clinical routine. The aim of this study was
to evaluate if cervical length measured by transvaginal sonography could assist
in the identification of women at high risk for IAI. METHODS: Cervical length was
assessed by transvaginal sonography in 87 women with singleton pregnancies in
preterm labor (<34 weeks of gestation). Cervical (n=87) and amniotic (n=55)
fluids were collected. Polymerase chain reactions for Ureaplasma urealyticum and
Mycoplasma hominis, and culture for aerobic and anaerobic bacteria, were
performed. Interleukin (IL)-6 and IL-8 were analyzed by enzyme-linked
immunosorbent assay. RESULTS: IAI was present in 25/55 (45%) of the patients
presenting with preterm labor who underwent amniocentesis. Women with IAI had a
significantly shorter cervical length (median, 10 (range, 0-34) mm) than had
those without IAI (median, 21 (range, 11-43) mm) (P<0.0001). Receiver-operating
characteristics curve analysis showed that a cervical length (cut-off of 15 mm)
predicted IAI (relative risk, 3.6; CI, 1.9-10.0) with a sensitivity of 72%,
specificity of 83%, positive predictive value of 78% and negative predictive
value of 78%. Cervical length was also significantly associated with preterm
birth up to 7 days from sampling and at 7.0 the ligand is unprotonated,
it stays inside the micelles and is quenching, while addition of Hg(2+) in the
7.0-9.5 pH range results in the formation of [C4-NS4Hg](2+), which is hydrophilic
enough to leave the micelles and to be released into the bulk solution where it
is no longer capable of quenching pyrene fluorescence. Additional studies on C1
NS4, C3-NS4 and C8-NS4 indicate that the optimal chain length to observe this OFF
ON behaviour is C(3)-C(4).
PMID- 17042049
TI - P(8) (8-) polyanion with phosphorus atoms in three different formal oxidation
states stabilized by a combination of Ag(+) and Hg(2+) cations.
PMID- 17042050
TI - Surface modification of a six-capped body-centered cube Ni9W6 cluster: structure
and single-molecule magnetism.
PMID- 17042051
TI - Selective electrochemical retro-cycloaddition reaction of pyrrolidinofullerenes.
PMID- 17042052
TI - A highly efficient palladium nanocatalyst anchored on a magnetically
functionalized polymer-nanotube support.
PMID- 17042053
TI - Reversible red fluorescent molecular switches.
PMID- 17042054
TI - Ankylosing spondylitis: a dual perspective of current issues and challenges.
AB - This series of articles on ankylosing spondylitis (AS) provides insight into the
burden of disease and focuses on early diagnosis and effective management. AS
leads to progressive functional impairment over time and has tremendous impact on
society at large in terms of economic costs and indirect costs associated with
physical impairment and loss of employment. Early diagnosis is crucial now that
we have more effective therapy with tumor necrosis factor (TNF) antagonists,
which suppress disease activity and improve the functional ability of patients
whose disease is refractory to conventional drug therapy. Early identification of
variables that help predict severe disease with bad functional prognosis is
needed. If biological therapy with TNF inhibitors is proven to retard disease
progression and prevent or delay functional limitations, insight into such
prognosticators will help us offer the correct treatment to the correct patient
at the correct time. There is also a need to demonstrate longterm benefits of
such a therapy as well as a favorable cost/benefit ratio to help convince
healthcare authorities, insurance companies, and others of the utility of these
drugs for treating patients with AS refractory to conventional drug therapy.
PMID- 17042055
TI - The burden of ankylosing spondylitis.
AB - The acute as well as chronic clinical features of ankylosing spondylitis (AS) are
a burden to the patient and society. Apart from the axial and articular
manifestations, extraarticular AS-related comorbidities such as uveitis,
inflammatory bowel disease, and psoriasis contribute to the burden of the
disease. In addition, a large proportion of patients have osteoporosis or
osteopenia, which may be associated with fractures and contribute to kyphosis.
All these features result in decreased quality of life. Moreover, patients with
AS have an increased mortality rate. The impact of this disease also can be seen
in various aspects of workforce participation, from requiring more assistance at
paid work to withdrawal from the workforce. Further, patients with AS and,
subsequently, society are affected by substantial healthcare costs related to
medications and healthcare provider expenses. Early diagnosis and management of
patients will likely prevent functional disability and improve patient outcomes.
PMID- 17042056
TI - Diagnosing ankylosing spondylitis.
AB - This article focuses on the early diagnosis and effective management of
ankylosing spondylitis (AS), a disease that is not uncommon and that can cause
early retirement and severe functional disability. AS, like most other
rheumatologic diseases, has no diagnostic gold standard. Correct diagnosis
depends largely on a constellation of clinical symptoms and signs in addition to
radiological findings. Early diagnosis has become all the more important because
effective therapies are available: tumor necrosis factor antagonists that
suppress disease activity and improve functional ability in patients with AS
refractory to conventional drug therapy. The biologic agents are probably even
more effective if given early. Inflammation of the sacroiliac joints and the
spine is a common, early feature and possibly the most frequent first
manifestation of disease. Therefore, its early detection is important, and
magnetic resonance imaging has proven useful in this regard. To optimize
diagnostic accuracy of early disease, it is crucial to use a comprehensive
approach and have a deep understanding of the disease and its clinical picture.
The clinician should gather a complete history, paying close attention to all the
elements of this multisystem disease, as well as judiciously ordering laboratory
testing and imaging. New strategies are being developed to assist primary care
physicians in their screening for these patients, which in turn should result in
early referral to rheumatologists and early diagnosis.
PMID- 17042057
TI - Treatment of ankylosing spondylitis.
AB - Ankylosing spondylitis (AS) is a condition characterized by inflammatory back
pain and associated with considerable disability and diminished quality of life
in affected individuals. The condition is undertreated in part due to a delay in
diagnosis and limited therapeutic interventions. Although traditional treatment
approaches (physical therapy, exercise, patient education, nonsteroidal
antiinflammatory drugs) remain important components of the management of AS, the
demonstrated efficacy of tumor necrosis factor-a (TNF-a) antagonists such as
etanercept and infliximab have allowed clinicians to more effectively manage this
condition. These targeted therapies have demonstrated rapid and consistent
effectiveness in reducing the axial and peripheral symptoms of AS, slowing
disease progression, and improving patient function and quality of life.
Appropriate and timely use of TNF-a antagonists offers additional options for
patients with active AS who are inadequately controlled with conventional
treatment.
PMID- 17042058
TI - From health to peace in Afghanistan--the story so far.
PMID- 17042059
TI - Socioeconomic stress and drug consumption: unemployment as an adverse health
factor in Croatia.
AB - AIM: To explore to what degree unemployment was related to health problems
expressed in terms of consumption of prescription drugs in Croatian citizens.
METHODS: Based on the Croatian Institute for Health Insurance data for 2003, the
number of prescriptions per insured individual (NPI) was calculated for employed
and unemployed persons, as well as for different subsets according to the region
(Zagreb, Split, Rijeka, Osijek), age, gender, and prescribed drug category.
RESULTS: During 2003, a total of 1 003 547 drugs were prescribed to 949 746
health-insured persons aged 18-69 years. NPI was 32% higher for unemployed than
for employed citizens; it averaged 0.995 among the employed, and 1.317 among the
unemployed. Differences in NPI (DeltaNPI) between the employed and the unemployed
varied within the subsets; the largest difference was observed in the Zagreb
region (DeltaNPI =0.522), in the 30-39 age group (DeltaNPI =0.563), in men
(DeltaNPI =0.565), and for anxiolytic/antidepressant drugs (DeltaNPI =0.184).
CONCLUSION: Our findings indicate that unemployed Croatian citizens used more
drugs, which calls for the implementation of health care measures to reduce or
prevent their medical problems, particularly those affecting mental health.
Medical problems associated with unemployment present a specific burden for
family medicine and the health care system.
PMID- 17042060
TI - Capecitabine as a radiosensitizing agent in neoadjuvant treatment of locally
advanced resectable rectal cancer: prospective phase II trial.
AB - AIM: To evaluate the efficacy and toxicity of preoperative chemoradiotherapy with
capecitabine in locally advanced rectal cancer. METHODS: Between June 2004 and
January 2005, 57 patients with operable, clinical stage II-III adenocarcinoma of
the rectum entered the prospective phase II study. Radiation dose was 45 Gy
(25x1.8 Gy). Concurrent chemotherapy with a daily dose of 1650 mg/m2 capecitabine
was administered orally, divided into two equal doses per day, including
weekends. Patients were evaluated weekly for acute toxicity and compliance with
the protocol. Surgery was scheduled 6 weeks after the completion of the
chemoradiotherapy. RESULTS: A single female patient died after receiving 27 Gy,
because of pulmonary embolism. All other patients completed the preoperative
chemoradiotherapy according to the protocol and a definitive operation was
performed in all but one of these patients. The complete pathological response
was recorded in 5 patients (9.1%). Tumor (T), lymph nodes (N), and overall
downstaging rates were 40%, 52.9%, and 49.1%, respectively. Total sphincter
preservation rate was 65.5% (36 out of 55 patients) and the rate in 27 patients
with tumors located within 5 cm of the anal opening was 37% (10 out of 27
patients). The most frequent side-effect of the combined therapy was dermatitis
(grade 3 in 19 patients). After surgery, a single patient died due to sepsis
during the early perioperative period. Nonlethal perioperative complications were
recorded in 24/55 patients. CONCLUSION: Preoperative chemoradiotherapy with oral
capecitabine is safe and well tolerated. It has a downstaging potential and can
increase the possibility for sphincter preservation surgery.
PMID- 17042061
TI - Antenatal assessment of discordant umbilical arteries in singleton pregnancies.
AB - AIM: To assess the relationship between discordant umbilical arterial size and
resultant blood flow parameters and determine the impact of discordance on fetal
outcome. METHODS: This is a descriptive, cross-sectional study of 200 patients
with a singleton gestation, who underwent a fetal anatomy survey between 18 to 23
weeks of gestation, with documented umbilical cord morphological patterns and
blood flow characteristics. Umbilical vessel diameters and Doppler parameters
(umbilical vein blood flow volume, mean resistance index, and peak-systolic
velocity) were analyzed for discordance. Discordances encountered were examined
for their possible association with perinatal outcome. RESULTS: We had adequate
ultrasound umbilical cord images, Doppler flow parameters, and all necessary
demographic data for 154 patients. Umbilical artery discordance averaged 13.1%
and was significantly correlated with both the expected and the true percent of
difference in resistance index values (RI, P<0.001). In 12 patients (7.8%), a
significant discordance of more than 29.5%, or 95th percentile, was observed
between the two umbilical artery diameters. However, in these cases no associated
adverse perinatal outcome or significant placental pathology was noted. There was
no significant difference between patients discordant or concordant umbilical
artery in terms of maternal, labor, and neonatal data. CONCLUSION: The magnitude
of umbilical arteries' luminal discordance directly influences the corresponding
blood flow parameters. In our sample of patients, the presence of discordant-in
size umbilical arteries was not associated with umbilical cord or placental
abnormalities.
PMID- 17042062
TI - Effects of age on plasma glucose levels in non-diabetic Hong Kong Chinese.
AB - AIM: To analyze the relationship between age and plasma glucose levels in Hong
Kong Chinese population. METHODS: We performed a cross-sectional study with
15,603 non-diabetic subjects from the community of Hong Kong. Plasma glucose
concentration was measured in blood specimens from the subjects. The time of
blood taking varied, depending on the availability of the patients. RESULTS:
There were 11,148 (71.4%) women and 4455 (28.6%) men (mean age: 50.1+/-16.1
years). There were 6901 (44.2%) patients who had plasma glucose measured in the
fasting condition, 2999 (19.2%) who were 2-hour post-prandial, and 5703 (36.6%)
who had plasma glucose measured at a random time. The correlation coefficients
between age and plasma glucose levels in fasting, 2-hour post-prandial, and
random group of patients were 0.159, 0.169, and 0.114, respectively (adjusted for
body mass index, smoking, and gender; all P values <0.001). Fasting and random
plasma glucose level increased by 0.15 mmol/L, while 2-hour post-prandial plasma
glucose level increased by 0.26 mmol/L per decade-increase in age. CONCLUSION:
Plasma glucose levels progressively increase with age in Hong Kong Chinese non
diabetic subjects.
PMID- 17042063
TI - Perinatal and maternal outcomes in Tuzla Canton during 1992-1995 war in Bosnia
and Herzegovina.
AB - AIM: To compare perinatal and maternal outcomes in Tuzla Canton during the 1992
1995 war in Bosnia and Herzegovina with those before (1988-1991) and after (2000
2003) the war. METHODS: We retrospectively collected data on a total of 59,707
liveborn infants and their mothers from the databases of Tuzla University
Department for Gynecology and Obstetrics and Tuzla Institute for Public Health.
Data on the number of live births, stillbirths, early neonatal deaths, causes of
death, gestational age, and birth weights were collected. We also collected data
on the number of medically unattended deliveries, examinations during pregnancy,
preterm deliveries, and causes of maternal deaths. Perinatal and maternal
outcomes were determined for each study period. RESULTS: There were 23,194 live
births in the prewar, 18,302 in the war, and 18,211 in the postwar period. Prewar
perinatal mortality of 23.3 per 1000 live births increased to 25.8 per 1000 live
births during the war (P<0.001), due to a significant increase in early neonatal
mortality (10.3 per thousand before vs 15.1 per thousand after the war, P<0.001).
After the war, both perinatal mortality (14.4 per thousand) and early neonatal
mortality (6.6 per thousand) decreased (P<0.001 for both). The most frequent
cause of early neonatal death during the war was prematurity (55.7%), with
newborns most often dying within the first 24 hours after birth. During the war,
there were more newborns with low birth weight (<2500 g), while term newborns had
lower average body weight. Women underwent 2.4 examinations during pregnancy (5.4
before and 6.3 after the war, P<0.001 for both) and 75.9% had delivery attended
by a health care professional (99.1% before and 99.8% after the war; P<0.001 for
both). Maternal mortality rate of 65 per 100,000 deliveries during the war was
significantly higher than that before (39 per 100,000 deliveries) and after (12
per 100,000 deliveries) the war (P<0.001 for both). CONCLUSION: Perinatal and
maternal mortality in Tuzla Canton were significantly higher during the war,
mainly due to lower adequacy and accessibility of perinatal and maternal health
care.
PMID- 17042064
TI - Prevalence of and risk factors for self-reported sexually transmitted infections
in Slovenia in 2000.
AB - AIM: To estimate the prevalence of self-reported sexually transmitted infections
(STIs) and examine the associations between self-reported STIs and
sociodemographic and behavioral factors among sexually active Slovenians aged 18
49 years. METHODS: Data were collected during 1999-2001 from a probability sample
of the general population at respondents' homes by a combination of face-to-face
interviews and anonymous self-administered questionnaires. Statistical methods
for complex survey data were used to account for stratification, clustered
sampling, and weighing. RESULTS: The proportion of sexually active Slovenian
population that reported ever being diagnosed with an STI, excluding pelvic
inflammatory disease and vaginal discharge for women, was 5.5% for men and 5.1%
for women. Gonorrhea was the most commonly self-reported STI among men (3.7%) and
hepatitis B among women (1.7%). Independent risk factors associated with self
reported STIs included having concurrent heterosexual relationships during
lifetime [adjusted odds ratio (AOR) for men 3.3 (CI 1.3-8.6) and for women 2.3
(CI 1.0-5.3)], ever having paid for sex for men (AOR 4.0, CI 1.5-10.7), and
having at least 10 lifetime heterosexual partners for women (AOR 4.7, CI 1.7
13.0). CONCLUSION: Our estimates of lifetime prevalence of self-reported STIs in
a probability sample of Slovenian men and women aged 18 to 49 indicate a
substantial national burden of STIs. The results could be used in shaping
national STI prevention and control policies and strategies. Identification of
risk factors associated with self-reported STIs provide a basis for targeting
prevention and control efforts to individuals at higher risk.
PMID- 17042065
TI - Consequences of domestic violence on women's mental health in Bosnia and
Herzegovina.
AB - AIM: To assess psychological consequences of domestic violence, and determine the
frequency and forms of domestic violence against women in Bosnia and Herzegovina.
METHODS: The study was carried out in the Tuzla Canton region in the period from
2000 to 2002, and included 283 women aged 43+/-9.6 years. Out of 283 women, 104
received psychiatric treatment at the Department for Psychiatry of the University
Clinical Center Tuzla, 50 women were refugees; and 129 were domicile inhabitants
of the Tuzla Canton. Domestic Violence Inventory, Cornell Index, Symptom
Checklist-90-Revised, PTSD Checklist Version for Civilians, and Beck Depression
Inventory were used for data collection. Basic sociodemographic data and
information from the medical documentation of the Department for Psychiatry of
the University Clinical Center Tuzla was also collected. RESULTS: Out of 283
women, 215 (75.9%) were physically, psychologically, and sexually abused by their
husbands. Among the abused, 107 (50.7%) experienced a combination of various
forms of domestic violence. The frequency of domestic violence was high among
psychiatric patients (78.3%). Victims of domestic violence had a significantly
higher rate of general neuroticism, depression, somatization, sensitivity,
obsessive-compulsive symptoms, anxiety, and paranoid tendency than women who were
not abused. The prevalence of posttraumatic stress disorder (PTSD) symptoms
according to the type of trauma was higher in women with the history of childhood
abuse (8/11) and domestic violence (53/67) than in women who experienced war
trauma (26/57) and the loss of loved ones (24/83). The majority of 104
psychiatric patients suffered from PTSD in comorbidity with depression (n=45),
followed by depression (n=17), dissociative disorder (n=13), psychotic disorder
(n=7), and borderline personality disorder with depression (n=7). The intensity
of psychological symptoms, depression, and Global Severity Index for
Psychological Symptoms (GSI) were in significant positive correlation with the
frequency of psychological (r=0.45, P<0.001), physical (r=0.43, P<0.001), and
sexual abuse (r=0.37, P<0.001). CONCLUSION: Domestic violence in various forms
had long-term consequences on mental health of women. This should be taken into
account when treating women with war-related trauma.
PMID- 17042066
TI - Domestic violence against women in Sivas, Turkey: survey study.
AB - AIM: To determine the self-reported prevalence of domestic violence and
associated risk factors in the Sivas province of Turkey. METHOD: Five hundred and
eighty-three households were chosen by the method of stratified random sampling.
The average age among women was 28.65+/-4.64. A total of 45.3% of women were in
30-34 age-group, 76.5% were housewives, and 91.2% were married. The data were
gathered by performing face-to-face interviews in participants' homes.
Demographic data were obtained by fill-in forms. RESULTS: We found a
statistically significant relationship among the types of violence and annual
income, type of family, education and occupation level of women, education level
of perpetrators, watching violent films, and childhood experience of emotional
abuse or negligence. Fifty-two percent of women were exposed to at least one type
of violence. Verbal violence was the most frequent type of violence (53.8%),
followed by physical violence (38.3%). About 45% of women exposed to violence
were in the 30-34 age group, 41.6% completed only primary schools, 73.6% were
housewives, 91.7% were married, 71.0% had been exposed to violence during their
childhood, and 45.2%, had been exposed to violence several times in a month.
Economic problems were reported as the most important reason for domestic
violence (31.4%). CONCLUSION: Our study found higher prevalence of domestic
violence than expected. As an important public health problem, domestic violence
requires a multidisciplinary approach to understand its causes and plan
preventive measures.
PMID- 17042067
TI - Mobbing, stress, and work ability index among physicians in Bosnia and
Herzegovina: survey study.
AB - AIM: To assess the frequency of reported mobbing and the association among
mobbing, working environment factors, stress, health outcome, personality type,
and work ability index in a sample of physicians in Bosnia and Herzegovina.
METHOD: We conducted a questionnaire survey using a validated self-reported
questionnaire among 511 physicians in national health sector of Bosnia and
Herzegovina. The questions covered five major categories of mobbing behavior.
Characteristics of the work, perceived work environment and its effects, stress,
health, and satisfaction with work and life were assessed by the standardized
abridged form of Occupational Stress Questionnaire (OSQ). A standardized
questionnaire Work Ability Index (WAI) was used to determine the relation between
mobbing and work ability. RESULTS: Of 511 surveyed physicians, 387 (76%)
physicians self-reported mobbing behavior in the working environment and 136
(26%) was exposed to persistent mobbing. More than a half of the physicians
experienced threats to their professional status and almost a half felt isolated.
Logistic regression analysis showed that lack of motivation, loss of self-esteem,
loss of confidence, fatigue, and depressiveness were significantly associated
with lack of support from colleagues. Intention to leave work was associated with
lack of support from colleagues (OR 2.3, 95% CI, 1.065-3.535; t =4.296, P =0.003)
and lack of support from superiors (OR 1.526, 95% CI, 0.976-2.076; t =5.753; P
=0.001). Isolation or exclusion and threats to professional status were
predictors for mental health symptoms. Persistent mobbing experience was a
significant predictor for sick leave. CONCLUSION: Exposure to persistent threat
to professional status and isolation or exclusion as forms of mobbing are
associated with mental health disturbances and lack of self-esteem and
confidence. Setting up a system of support for physicians exposed to mobbing may
have important benefits.
PMID- 17042068
TI - Between stigma and dawn of medicine: the last leprosarium in Croatia.
AB - In an attempt to reconstruct the function of the last leprosarium in Croatia,
situated in the little town of Metkovic in the Neretva valley, we used local folk
tales and compared them with different data sources, such as register of deaths
in the Roman Catholic parishes in Metkovic and the nearby village of Vidonje,
archived local newspapers, building documents, and different artifacts from the
beginning of the 20th century. We identified individuals and families who were
treated in the leprosarium during its existence from 1905, when it was built,
until 1925, when it was closed down. We analyzed why the Neretva river valley was
chosen for the isolation of lepers. It seems that the geographical position of
the region, close to the endemic seat of the disease in the neighboring Bosnia,
was more important for the decision to build the leprosarium than the incidence
of leprosy or some recent outbreak of the disease in Croatia. Building of
leprosariums, such as this one in Metkovic, was a part of tradition of separating
lepers from human community. This was considered as a socially and medically
justified behavior in a time when it was not possible to identify the cause of
leprosy and apply the proper treatment.
PMID- 17042069
TI - Introductory course on getting to know journals and on "browsing" a research
paper: first steps to proficiency in scientific communication.
AB - AIM: To evaluate the effectiveness and appropriateness of a course that promotes
familiarity with biomedical periodicals and teaches efficient reading skills.
METHODS: A 16-hour course was designed to help inexperienced readers gain
confidence navigating the contents of a research paper (instead of reading only
abstracts), and make the first steps to critical appraisal. The course consisted
of short lessons and small group work in which research papers were read and
presented to the class. Participants learned a method called "browsing" that
guides the first, superficial reading of a research paper and substitutes
abstract reading. The course was administered to 15 hospital physicians and 40
graduate students of molecular medicine, in 4 separate sessions. RESULTS: At
course entry, 45 of 55 participants normally read the abstract before consulting
the body of a research paper. An end-of-course questionnaire, completed by 47
participants, revealed that only 3 would still read the abstract first, while 33
would perform browsing, 7 would scan figures and tables, and 4 would consult
another section of a paper outside of their research interests; similar responses
were given for a research paper within their fields. For 43 participants, the
course was effective in developing reading skills. On a final comprehension test,
participants had a median score of 69% correct responses (interquartile range,
56%-80%). CONCLUSION: This introductory course on reading scientific articles is
effective in overcoming abstract-only reading and in developing confidence with
the research literature. Considering participants' subjective evaluation and test
scores, the course contents are appropriate for both physicians and young
researchers.
PMID- 17042071
TI - 34.8 degrees C and rising.
PMID- 17042070
TI - Scientific production of research fellows at the Zagreb University School of
Medicine, Croatia.
AB - AIM: To evaluate scientific production among research fellows employed at the
Zagreb University School of Medicine and identify factors associated with their
scientific output. METHOD: We conducted a survey among research fellows and their
mentors during June 2005. The main outcome measure was publication success,
defined for each fellow as publishing at least 0.5 articles per employment year
in journals indexed in the Current Contents bibliographic database. Bivariate
methods and binary logistic regression were used in data analysis. RESULTS: A
total of 117 fellows (response rate 95%) and 83 mentors (100%) were surveyed. The
highest scientific production was recorded among research fellows employed in
public health departments (median 3.0 articles, interquartile range 4.0),
compared with those from pre-clinical (median 0.0, interquartile range 2.0) and
clinical departments (median 1.0, interquartile range 2.0) (Kruskal-Wallis, P
=0.003). A total of 36 (29%) research fellows published at least 0.5 articles per
employment year and were considered successful. Three variables were associated
with fellows' publication success: mentor's scientific production (odds ratio
[OR], 3.14; 95% confidence interval [CI], 1.31-7.53), positive mentor's
assessment (OR, 3.15; 95% CI, 1.10-9.05), and fellows' undergraduate publication
in journals indexed in the Current Contents bibliographic database (OR, 4.05; 95%
CI, 1.07-15.34). CONCLUSION: Undergraduate publication could be used as one of
the main criteria in selecting research fellows. One of the crucial factors in a
fellow's scientific production and career advancement is mentor's input, which is
why research fellows would benefit most from working with scientifically
productive mentors.
PMID- 17042072
TI - Specialist training programs for African physicians.
PMID- 17042080
TI - Outbreak news. Avian influenza, Egypt--update.
PMID- 17042081
TI - Addressing the threat of tuberculosis caused by extensively drug-resistant
Mycobacterium tuberculosis.
PMID- 17042082
TI - The underrecognized burden of influenza.
PMID- 17042083
TI - The underrecognized burden of influenza.
PMID- 17042084
TI - Hospital volume and outcomes of mechanical ventilation.
PMID- 17042085
TI - Intensive care of patients with HIV infection.
PMID- 17042086
TI - [Very good effect of Hib vaccination in Kenya].
PMID- 17042087
TI - Tooth sensitivity and whitening.
AB - This article presents a review of the basic concepts of tooth sensitivity and how
those concepts apply to cervical dentin hypersensitivity and the sensitivity
frequently associated with tooth whitening. The etiology and treatment of
cervical dentin hypersensitivity are described. The clinical presentation,
incidence, and predisposing factors for sensitivity associated with tooth
whitening also are discussed.
PMID- 17042088
TI - Balanced force and rotary shaping.
AB - Studies on instrument performance in clear acrylic canals have Professor Emeritus
of Endodontics indicated that the helical angle of the cutting edge is a
contributing factor Oklahoma City Oklahoma in instrument overload and failure. In
clinical trials, changing the design of modern shaping instruments to eliminate
the inclined angulations of the Private Practice in Endodontics cutting edges has
proven to be beneficial by reducing the risk of fracture. Norman, Oklahoma Yet
another benefit of a nonhelical cutting edge is that the flute space is
accessible past the segment so that the fragment can be bypassed rather easily
and the apex can be shaped with hand instruments. It appears that this feature
may reduce the impact of a separated instrument.
PMID- 17042089
TI - Endodontic and esthetic/restorative treatment of the same tooth: a synergistic
approach for successful outcomes.
AB - Endodontic and restorative treatment of compromised teeth should not be
considered separate, unrelated procedures. It is beneficial for both the
endodontist and the restorative dentist to consider the other's treatment of a
patient with compromised teeth. Both practitioners should thoroughly understand
their respective modalities and the ways in which their work affects the
remaining structure and integrity of the teeth being treated. The restorative
dentist also should be aware that there are 2 primary goals of endodontic
treatment: cleaning and disinfecting the affected canals, and sealing those
canals to prevent reinfection. The endodontist should be aware that the
objectives of the restorative dentist are to ensure postoperative root strength,
prevent vertical root fracture, and retain the core of the restoration. This
article describes a synergistic approach to treating teeth requiring both
endodontic and restorative treatment.
PMID- 17042090
TI - Recent article on Thomas Evans.
PMID- 17042091
TI - The management of abuse: 2. Child abuse.
AB - The role of the GDP and the dental team in the recognition and management of
child abuse is discussed. Information on the current legislation and protocols
for referral are provided. CLINICAL RELEVANCE: This paper discusses child abuse
and offers information and practical advice for the dental team.
PMID- 17042092
TI - [Effect of potassium level on output and diosgenin content of Dioscorea
zingiberensisg].
AB - OBJECTIVE: To study the effect of potassium level on physiological
characteristics and diosgenin content of Dioscorea zingiberensisg and provide
experimental basis for proper use of potassium fertilizer. METHODS: Field
experiment including four potassium levels was carried out. The physiological
characteristics of leaves were determined at different growth stages and the
diosgenin content in bulk root was assayed after harvest. RESULTS: Within the
arrange of 0-180 kg K2SO4/hm2, the content of chlorophyll and amino acid, Fv/Fo,
Fv/Fm, and phiPs II were increased with the increase in potassium level.
Meanwhile, the ability to defense the damage caused by active oxygen was
obviously enhanced. Further increase in potassium level resulted in the decrease
in efficiency of potassium fertilizer. CONCLUSION: It indicats that higher yield
and diosgenin content can be obtained when the potassium level is 180 kg K2/hm2.
PMID- 17042093
TI - High-dose, single-bolus eptifibatide: a safe and cost-effective alternative to
conventional glycoprotein IIb/IIIa inhibitor use for elective coronary
interventions.
AB - BACKGROUND: Adjunctive pharmacotherapy with eptifibatide, a glycoprotein (GP)
IIb/IIIa inhibitor, as an intravenous bolus followed by infusion has been shown
to improve outcomes in elective coronary interventions (PCI). However, bleeding
complications and costs have limited the routine adoption of this regimen.
PURPOSE: The goal of this study was to examine the safety, efficacy and cost
effectiveness of high-dose, single-bolus eptifibatide, without post-intervention
infusion, in "real-world" patients undergoing elective PCI. METHODS: We studied
401 patients with stable and unstable angina who were treated with a high-dose
(20 mg), single bolus of eptifibatide plus heparin prior to the start of elective
PCI. Exclusion criteria included recent MI, stenting of bypass graft(s),
rotational atherectomy and/or brachytherapy. The primary study endpoints were
major adverse clinical events (MACE), defined as the in-hospital and 30-day
incidence of death from any cause, Q-wave or non-Q-wave MI, repeat target vessel
revascularization and/or major bleeding complications. RESULTS: Relevant
demographic and procedural characteristics included mean age: 66.4 +/- 11.2; male
gender: 242/401 (61%); number of vessels treated per patient: 1.46 +/- 0.42; and
number of stents deployed per patient: 1.82 +/- 0.65. In-hospital non-Q-wave MI
(CPK and/or CPK-MB > 3 times the upper limit of normal) occurred in 7/401
patients (1.75%) and MACE was 2.25%. Major bleeding complications were seen in
2/401 patients (0.49%). There were 4 additional MACE events at 30-day follow up
(total MACE and bleeding = 3.25%). The average anticoagulation cost was 66
dollars/patient. CONCLUSIONS: Intravenous eptifibatide, administered as a high
dose (20 mg) single-vial bolus, is a safe, effective and highly cost-effective
alternative to the conventional regimens of bolus plus prolonged intravenous GP
IIb/IIIa inhibitor infusion for patients undergoing elective PCI.
PMID- 17042094
TI - Five-year clinical follow up after intracoronary radiation for the prevention of
in-stent restenosis.
AB - Intracoronary radiation therapy (IRT), utilizing both gamma- and beta-emitting
radiation sources, is considered to be a safe and effective treatment for in
stent restenosis (ISR). Although no longer in clinical use, a significant number
of patients were treated in the past with IRT, and their long-term outcomes have
not been well documented. The aim of the present analysis was to document the
long-term outcomes of all patients who underwent IRT at our institution for the
prevention of recurrence of ISR. Data were collected from 132 patients (148
irradiated lesions) treated with IRT at our institution between March 1999 and
January 2004. Clinical and angiographic data were collected over a 5-year period.
Patients were divided into 2 groups: those with failed IRT (n = 65), defined as a
procedure that resulted in a major adverse cardiac event: death, myocardial
infarction, target lesion revascularization, target vessel revascularization or
coronary artery bypass graft surgery at any time during the follow-up period, and
patients with successful IRT (n = 67). Both groups were identical regarding
baseline clinical and angiographic characteristics, with the exception of a
higher percentage of multivessel disease and diffuse restenosis in patients who
failed IRT (p = 0.01). At 1-year follow up, slightly less than half (43%) of
those patients in the failure group experienced a major adverse cardiac event.
During the long-term follow up period, half of all patients who underwent IRT at
our institution experienced a major adverse cardiac event, 61 patients (46%)
either died or underwent a revascularization procedure, 16 patients (24%) had a
myocardial infarction or died, and 55 patients (42%) required repeat coronary
revascularization. The average time to develop a major adverse cardiac event was
14.6 +/- 15 months. Therefore, during long-term follow up following IRT for the
prevention of ISR, half of all patients developed a major cardiovascular event,
mainly due to the need for repeat revascularization procedures.
PMID- 17042095
TI - Commentary: Alternative safe, effective and cost-efficient dosing for
eptifibatide in low-risk patients.
PMID- 17042096
TI - Commentary: Can distal embolic protection yield better results in acute
myocardial infarction treatment?
PMID- 17042097
TI - Commentary: Bifurcations: the problem is the side branch.
PMID- 17042098
TI - Distal protection during primary angioplasty: a feasibility and safety study
utilizing a novel filter technology.
AB - BACKGROUND: The degree of myocardial reperfusion after primary percutaneous
coronary intervention (PCI) may be reduced by distal embolization. We tested the
safety, feasibility and efficacy of a novel filter device, the Spider Distal
Embolic Protection System, as an adjunct to primary PCI. METHODS AND RESULTS:
Twenty consecutive patients undergoing primary PCI with the Spider Embolic
Protection Device were included in the analysis. Successful Spider device
positioning was obtained in all cases, with predilatation of the lesions in 1 of
these cases (5%). There were no procedural complications attributable to the use
of a filter. Histological analysis of the content of 5 filters showed multiple
embolic debris in all cases, from 8 to 48 particles per filter, from 101-1,299 mm
in diameter and from 212-1,487 mm2 in area. The use of the Spider filter was
associated with a profound ST-segment resolution (STR: 85.6 +/- 16.5%) and the
occurrence of complete (50%) STR of 90%. CONCLUSIONS: The Spider Embolic
Protection Device as an adjunctive therapy during primary PCI is feasible and
safe, preventing distal embolization and improving myocardial reperfusion.
Currently, an international, multicenter, randomized clinical trial is
prospectively testing this challenging hypothesis.
PMID- 17042099
TI - Medicaid program; state allotments for payment of Medicare Part B premiums for
qualifying individuals: federal fiscal year 2006 and fiscal year 2007. Final
rule.
AB - This final rule sets forth the methodology and process used to compute and issue
each State's allotments for fiscal years (FY) 2006 and FY 2007 that are available
to pay Medicare Part B premiums for qualifying individuals. It also provides the
final FY 2006 allotments and the preliminary FY 2007 allotments determined under
this methodology. We are also confirming the April 28, 2006 interim final rule as
final.
PMID- 17042100
TI - Assessment of FFR-negative intermediate coronary artery stenoses by spectral
analysis of the radiofrequency intravascular ultrasound signal.
AB - BACKGROUND: Assessing the clinical importance of angiographically intermediate
coronary artery stenoses at the time of cardiac catheterization remains a
challenge. Spectral analysis of radiofrequency ultrasound backscatter signals, or
virtual histology (VH), allows in vivo assessment of plaque composition. This
study characterizes the VH composition of fractional flow reserve (FFR)-negative
intermediate stenoses and adjacent vessel segments. METHODS: Intermediate
coronary artery stenoses (> 40% and < 70% diameter stenosis) were assessed by
pressure wire. If the FFR was > or = 0.75, percutaneous coronary intervention was
deferred and VH was performed on the lesion and adjacent segments using a
commercially available system. The primary clinical endpoint was any adverse
cardiac event. RESULTS: Thirty-seven intermediate stenoses in 30 patients were
studied. The reference vessel size was 3.02 +/- 0.71 mm, the QCA diameter
stenosis was 52 +/- 6% and the FFR was 0.89 +/- 0.07. The target stenoses were
characterized by VH as: thin-cap fibroatheroma (VH-TCFA; n = 22); fibrous cap
atheroma (n = 5), fibrocalcific lesion (n = 7) and pathological intimal
thickening (n = 3). The relative contribution of each stenosis plaque component
was conserved across adjacent segments ("signature" plaque). Three patients, all
with VH-TCFAs at index, had events in the clinical follow-up period of 12 +/- 2
months, but only 1 of these patients had an event related to the index stenosis.
CONCLUSIONS: FFR-negative intermediate stenoses have heterogeneous plaque by VH,
but are enriched in VH-TCFAs. Relative plaque composition is conserved along
adjacent vessel segments. Although the specificity of VH-TCFA for index stenosis
related events appears low, larger trials are needed to assess the prognostic
value of VH in this lesion subset.
PMID- 17042101
TI - Balloon alignment T-stenting for bifurcation coronary artery disease using the
sirolimus-eluting stent.
AB - OBJECTIVE: The purpose of this study was to evaluate the long-term outcomes of
bifurcation coronary lesions treated with a novel technique called "balloon
alignment T-stenting". BACKGROUND: The optimal technique for the treatment of
bifurcation coronary disease has not yet been established. METHODS: Twenty-six
patients with bifurcation coronary lesions were treated with currently available
drug-eluting stent (DES) platforms. This was a pilot study to determine the long
term efficacy of a novel technique, "balloon alignment T-stenting". Based on this
technique we performed 6-month anniversary angiography to determine restenosis
rates for both main and side branch lesions treated. RESULTS: Twenty-six main
branches and 27 side branches were treated with this novel technique.
Angiographic 6-month follow up was available for all 26 patients treated. There
were no postprocedural mortalities and no cases of postprocedural stent
thrombosis during the follow-up period. At 6-month anniversary angiography, no
evidence of main branch restenosis was seen. However, there were 2 cases of side
branch restenosis for a total side branch restenosis rate of 7.4%. Target lesion
revascularization for the 26 patients in the study was 7.6%. The total major
adverse cardiac event rate for the group as a whole was 15.4%, with 2
periprocedural non-Q-wave myocardial infarctions and 2 target lesions requiring
revascularization at 6 months. CONCLUSION: Using currently available DES
platforms, the data compiled from this small, single-center pilot study suggest
that balloon alignment T-stenting may represent a reasonable approach for the
treatment of bifurcation coronary artery disease. However, more comprehensive,
larger-scale trials will be required to validate these preliminary findings.
PMID- 17042102
TI - Titanium and nitride oxide-coated stents and paclitaxel-eluting stents for
coronary revascularization in an unselected population.
AB - The aim of this study was to compare clinical outcome of a stainless-steel stent
coated with titanium nitride oxide (TITANOX) and a paclitaxel-eluting stent (PES)
in routine clinical practice represented by two prospective registries including
all patients with de novo coronary artery disease treated exclusively with a
TITANOX stent (n = 201) or with a PES (n = 204) between May 2003 and November
2004 (63% of all PCI patients). The primary endpoint of the study was major
adverse cardiac events (MACE) at 30 days and 12 months. The TITANOX stent
patients were more frequently (p = 0.011) treated for acute myocardial infarction
and had more complex B- and C-type lesions (p = 0.004). The PES patients had
longer (p < 0.001) total stent length. At 30 days, the rate of MACE was 0% and
4.9% for the TITANOX stent and PES groups, respectively (p = 0.001). A
significant difference in target vessel revascularization (TVR) was seen in favor
of the TITANOX stent (0% vs. 2.9% for PES; p = 0.014). This was mainly driven by
stent thrombosis (n = 7). At 12 months, the difference in MACE was no longer
significant (10.9% vs. 13.7%; p = 0.40), but the rate of myocardial infarction
was lower in the TITANOX stent group (4.5% vs. 10.3%; p = 0.025). The rate of TVR
(8% vs. 6.9%; p = 0.67) was similar between the two groups. In conclusion, both
the TITANOX-coated stent and PES resulted in good clinical outcome with
infrequent need for repeat interventions in the real-world setting of high-risk
patients and complex coronary lesions.
PMID- 17042103
TI - Automated contrast injection in contemporary practice during cardiac
catheterization and PCI: effects on contrast-induced nephropathy.
AB - OBJECTIVES: To evaluate the incidence of contrast-induced nephropathy (CIN) with
the use of an automated contrast injection system in conjunction with
contemporary measures to prevent CIN after cardiac catheterization and
percutaneous coronary intervention (PCI). BACKGROUND: The use of automated
contrast injection systems can reduce the volume of procedural contrast, but
whether lower contrast volume is associated with a lower incidence of CIN is
uncertain. METHODS: The incidence of CIN was assessed in 1,798 patients after
diagnostic catheterization or PCI at Wake Forest University Baptist Medical
Center from April 2002 to November 2004 using traditional handheld manifold
injection systems, and in 377 subsequent patients using an automated contrast
injection system. Preprocedural hydration was used on a routine basis, and N
acetylcysteine and bicarbonate infusion were used on an ad hoc basis. Outcomes
were adjusted by standard logistic regression modeling. RESULTS: Mean contrast
volume (+/- standard deviation) per case was reduced from 204 +/- 147 ml to 146
+/- 108 ml, p < 0.05 by use of automated contrast injection. The incidence of CIN
was 19.3% using manifold injection, and was 13.3%, p < 0.05, after use of
automated contrast injection. The use of automated contrast injection was
associated with a reduced relative risk of CIN, 0.66 (0.47-0.93), compared to
manual injection, even after adjustment for baseline clinical and procedural
covariates. CONCLUSIONS: The use of an automated contrast injection system in
conjunction with contemporary hydration and pharmacologic strategies to prevent
CIN during diagnostic catheterization and PCI was associated with a significant
reduction in the use of contrast volume, as well as in the incidence of CIN.
PMID- 17042104
TI - R (on the application of Quintavalle) v Secretary of State for Health.
PMID- 17042105
TI - R (Quintavalle) v Human Fertilisation and Embryology Authority (Secretary of
State for Health Intervening).
PMID- 17042106
TI - R (on the application of Quintavalle) v Human Fertilisation and Embryology
Authority.
PMID- 17042107
TI - R (On the application of Quintavalle) v Secretary of State for Health.
PMID- 17042108
TI - AB v Leeds Teaching Hospital NHS Trust.
PMID- 17042109
TI - The grapes of wrath.
PMID- 17042110
TI - Microorganisms and clean energy.
PMID- 17042111
TI - Not every cell is sacred: a reply to Charo.
AB - Massimo Reichlin, in an earlier article in this journal, defended a version of
the 'argument from potential' (AFP), which concludes that the human embryo should
be protected from the moment of conception. But R. Alto Charo, in her essay
entitled 'Every Cell is Sacred: Logical Consequences of the Argument from
Potential in the Age of Cloning', claims that versions of the AFP like Reichlin's
are vulnerable to a rather embarrassing problem: with the advent of human
cloning, such versions of the AFP entail that every somatic cell in the human
body ought to be protected. Since this entailment is clearly absurd, Charo
argues, these versions of AFP should be rejected. I argue that the reasons Charo
cites for believing in this entailment are inconclusive. For example, the four
reasons she gives for doubting any differences between the nature of skin cells
and zygotes are ultimately unconvincing. Against Charo, I maintain that there is
a relevant distinction between the sort of potential possessed by the somatic
cell and the sort of potential possessed by the early human embryo. Since only
the latter sort of potential falls within the scope of the AFP, the alleged
absurd entailment Charo invites us to consider is no entailment at all. Hence the
AFP cannot be rejected on the grounds Charo advances. Even in an age of cloning,
the claim that some cells are 'sacred' because of their potential does not entail
the claim that every cell is sacred.
PMID- 17042112
TI - Should children and adolescents be tested for Huntington's disease? Attitudes of
future lawyers and physicians in Switzerland.
AB - The objective of the study was to identify future lawyers' and physicians' views
on testing children for Huntington's disease (HD) against parents' wishes. After
receiving general information about HD, patient autonomy and confidentiality, law
students and advanced medical students were shown an interview with a mother
suffering from HD who is opposed to informing and testing her two children (aged
10 and 16) for HD. Students then filled out questionnaires concerning their
agreement with testing. No significant differences were found between medical and
law students or between students from different courses concerning the adolescent
son. Three quarters of students thought that he should be told about his mother's
disease, and 91% thought the adolescent son should have the opportunity of
genetic testing for HD himself. However, significant differences were found
concerning the 10-year old son, with 44% of law students and 30% of medical
students in favour of testing the child for HD. Students raised some important
ethical issues in their elective comments. In conclusion, we found highly
positive attitudes towards informing a 16-year old of his mother's HD and
offering to test him. These attitudes were not in tune with guidelines. Students
did not consider several practical and ethical issues of genetic testing of
children and adolescents. Specific education should ensure that attitudes are
based on sufficiently detailed knowledge about all aspects of genetic testing of
children to discourage pressures on persons at risk of HD.
PMID- 17042113
TI - Inconsistencies in pro ANT-OAR position.
PMID- 17042114
TI - Prospects for pluripotent stem cells: a reply to Communio.
PMID- 17042115
TI - A contralife argument against altered nuclear transfer.
PMID- 17042116
TI - The embryo as person.
PMID- 17042117
TI - Freedom at the end of life: voluntary death versus human flourishing.
PMID- 17042118
TI - Euthanasia: an uncontrollable power over death.
PMID- 17042119
TI - Welcoming the child at birth.
PMID- 17042120
TI - A case studies approach to assisted nutrition and hydration.
PMID- 17042121
TI - Human cloning and embryonic stem cell research after Seoul: examining
exploitation, fraud and ethical problems in the research. Testimony of Richard M.
Doerflinger.
PMID- 17042122
TI - Terrorism and dispelling the myth of a panic prone public.
AB - Governments and commentators perceive the public to be prone to panic in response
to terrorist attacks--conventional or involving chemical, biological or
radiological weapons. Evidence from five such incidents suggests that the public
is not prone to panic, although people can change their behaviours and attitudes
to reduce the risk of themselves being exposed to a terrorist incident.
Behavioural responses may be divided into acts of omission, such as not making
unnecessary journeys, and acts of commission, such as taking prophylactic
medication despite the inherent risk of side effects. Evidence suggests that the
public are aware of these differences, and tend to adopt responses proportionate
to the risk. Drawing upon the literature in the social and natural sciences, our
discussion encompasses differing risk perceptions of terrorist threats and
consequences of attacks. How do fear and anxiety interact with behavioural
responses to amplify or attenuate perceptions that can be modified through risk
communication undertaken by authorities?
PMID- 17042123
TI - The effects of obesity on doctor-diagnosed chronic diseases in Africa: empirical
results from Senegal and South Africa.
AB - While inadequate food and communicable infectious diseases have been a concern of
researchers and policy makers in Africa, little attention has been given to
obesity and chronic, non-communicable diseases. Africa is not usually associated
with obesity and chronic diseases. Yet there has been a sharp rise in the
incidence of obesity and chronic diseases, a major public health problem in many
countries. The paper examines the impact of obesity on the prevalence of four
doctor-diagnosed chronic diseases in Senegal and South Africa. The results reveal
that obese respondents were 4.7, 2.8, and 4.8% more likely to face the risks of
arthritis, diabetes, and heart diseases in South Africa and 6.5 and 7.4% more
likely to face the risks of heart disease and asthma in Senegal than their lean
counterparts. Obesity imposes a real and substantial danger, affecting the
prevalence of chronic diseases. Unchecked it can be a major public health
problem, impose a serious challenge to the health sector, and can jeopardize
future developments.
PMID- 17042124
TI - Setting health priorities across nations: more convergence than divergence?
AB - Recently, various theories of convergence of health care systems have been
presented. This review of several dimensions of health priority setting in nine
countries sheds light on the interrelationship between convergence and
embeddedness. It reconfirms that within a co-existence of convergence and
divergence, there are clusters of convergence, primarily at the ideational and
social value levels. However, our findings suggest that the variation across
different substantive levels is less clear cut than suggested by others.
Moreover, the variation between different procedural aspects of convergence
appears more significant. Certain ideas involving the need for rationing, the
role of market mechanisms, and cost containment have gained recognition by health
policy makers across countries, but this has not guaranteed their adoption. Our
analysis demonstrates that despite these signs of a convergence at the conceptual
level, policy content and the preferred policy instruments for implementing such
policy continue to vary widely across these countries.
PMID- 17042125
TI - Evidence against breast self examination is not conclusive: what policymakers and
health professionals need to know.
AB - Breast cancer is a serious health concern and a disease that is not well
understood. Early detection remains the best way to prevent debilitation and
death. Traditionally, mammography, clinical breast examination (CBE), and breast
self examination (BSE) have been accepted as legitimate breast screening
modalities. Over the past 5 years, academics, health professionals, and
policymakers have seriously questioned the usefulness of BSE after influential
organizations such as the Canadian Task Force on Preventive Health Care
downgraded their BSE recommendation citing fair evidence of no benefit and good
evidence of harm. We briefly review the three large BSE trials, highlighting
methodological weaknesses limiting their ability to evaluate its effectiveness,
as well as critique the 2001 Canadian Task Force on Preventive Health Care report
on BSE. We argue that it is premature to conclude that BSE is ineffective. Given
that most women find their own breast cancer, this article cautions policymakers
and health professionals that a prudent approach to BSE promotion should be
taken.
PMID- 17042126
TI - Policy needs regarding the duty to protect in epidemiological research with high
risk populations.
AB - The paper presents an analysis of policy directives needed to respond to threats
of harm (e.g., violence against third parties) that may arise in the course of
conducting descriptive epidemiological research with high-risk populations. It
identifies two key areas where new policies must be developed to guide
researchers conducting such investigations. The paper recommends that: (1) an NIH
consensus panel be convened to set standards, analogous to Common Toxicity
Criteria (CTC) criteria, to classify the severity of different types of indirect,
non-research-related risk; and (2) case-based training modules be developed and
incorporated into public health research ethics courses and training programs, to
enhance researcher judgments in determining the likelihood of harm in different
situations. In addition, researchers, Institutional Review Boards (IRBs) and
community advisory groups must consider the issue of staff safety and the
effectiveness of available responses to reduce the threat of harm. The author
reviews and discusses implications for informed consent and IRB review.
PMID- 17042127
TI - The Federation's Pages. Public health workforce, the new role.
PMID- 17042128
TI - Lombardy poplar.
PMID- 17042129
TI - Specific polysaccharide antibody deficiency.
PMID- 17042130
TI - Pathogenesis and recent therapeutic trends in Stevens-Johnson syndrome and toxic
epidermal necrolysis.
AB - OBJECTIVE: To review the current pathophysiologic mechanisms and recent
therapeutic trends in Stevens-Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN). DATA SOURCES: A MEDLINE search for SJS and TEN in combination
with Fas, Fas ligand (FasL), cytotoxic T cells, intravenous immunoglobulin, and
cyclosporine for articles published in English during 1966 to 2006. STUDY
SELECTION: Information was derived from original research articles and reviews
published in peer-reviewed journals. RESULTS: The hallmark of SJS and TEN is
epidermal cell apoptosis, which may be mediated through keratinocyte Fas-FasL
interaction or through cytotoxic T-cell release of perforin and granzyme B.
Whereas systemic corticosteroid therapy showed contradictory results, intravenous
immunoglobulin (IVIG) and cyclosporine have shown promising outcomes. IVIG
contains anti-Fas antibodies that can abrogate apoptosis when preincubated with
keratinocytes. Most studies on IVIG in SJS and TEN reported improvement in
arresting disease progression and reduction in time to skin healing. Because of
variations among studies, the findings cannot be optimally compared. In general,
mortality varied from 0% to 12% in studies that supported the use of IVIG and 25%
to 41.7% in those that did not demonstrate a beneficial effect. Cyclosporine
inhibits CD8 activation and thus may reduce epidermal destruction. Relatively few
case reports and 1 case series have been published regarding the use of
cyclosporine in SJS and TEN. In general, cyclosporine was associated with a
significant improvement in time to disease arrest and to complete
reepithelization, with no reported fatalities. CONCLUSIONS: Both IVIG and
cyclosporine have been associated with enhanced healing and better survival
through inhibition of apoptosis. Multicenter, randomized, placebo-controlled
trials using a standardized design are needed to validate these findings.
PMID- 17042131
TI - Lack of cross-reactivity between 5-aminosalicylic acid-based drugs: a case report
and review of the literature.
AB - BACKGROUND: 5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of
therapy in inflammatory bowel disease, but adverse reactions to these medications
are relatively common. Because there may be a lack of cross-reactivity among the
various 5-ASA formulations, treatment with alternative preparations is sometimes
possible even after an apparent allergic reaction to a 5-ASA product. OBJECTIVE:
To describe a patient with a possible allergy to 2 different 5-ASA drugs who
tolerated a third. METHODS: A 27-year-old man with Crohn disease developed a rash
while taking mesalamine (Pentasa and Asacol). Treatment with 5-ASA products was
discontinued, and 6-mercaptopurine and prednisone were prescribed. He then
experienced multiorgan failure secondary to herpes simplex infection, which
required discontinuation of the immunosuppressive therapy. After recovery from
the acute infection, he underwent successful graded challenge with balsalazide.
RESULTS: The patient continued treatment with balsalazide for 9 months, with good
control of his inflammatory bowel disease and no adverse effects. CONCLUSIONS:
Adverse reactions to 1 or more 5-ASA medications do not necessarily preclude the
use of others in the same class. A treatment algorithm for patients with adverse
reactions to 5-ASA is outlined based on the case report and review of the
literature.
PMID- 17042132
TI - Improvement of asthma control with omalizumab in 2 obese pediatric asthma
patients.
AB - BACKGROUND: Dosing of the anti-IgE antibody (omalizumab) in the treatment of
allergic asthma depends on serum IgE concentration and body weight. It is unclear
whether omalizumab is therapeutically effective in obese patients with difficult
to-control asthma whose body weights fall outside dosing guidelines. OBJECTIVE:
To report the efficacy of omalizumab in 2 obese pediatric patients with severe
persistent asthma whose high body weights placed them outside current dosing
guidelines. METHODS: Omalizumab was given at maximum doses to both patients.
Standard asthma therapy was continued throughout the treatment period. Multiple
parameters of asthma disease activity were followed at every health encounter for
approximately 1 year during and before omalizumab treatment. These parameters
included asthma disease severity and activity, pulmonary functions, daily inhaled
corticosteroid requirements, systemic steroid rescue, and urgent care and
emergency department visits and hospitalizations. RESULTS: While receiving
omalizumab, both patients had improvements in asthma disease activity and
reduction in systemic steroid requirements. One patient required fewer daily
inhaled corticosteroids and achieved total asthma control. CONCLUSION: Patients
with difficult-to-treat asthma may benefit from receiving omalizumab even if they
fall outside current dosing guidelines because of high body weight.
PMID- 17042133
TI - Clustered sensitivity to fungi: anaphylactic reactions caused by ingestive
allergy to yeasts.
AB - BACKGROUND: Respiratory allergy to environmental molds is relatively common, and
fungal allergen-specific reactivity seems to cluster in certain persons. However,
generalized reactions caused by ingested fungi have seldom been described.
OBJECTIVE: To describe a mold-sensitized patient who developed multiple
anaphylactic reactions after ingesting a yeast preparation widely used by the
food industry as flavoring in, for example, powdered and ready-made sauces.
METHODS: Skin prick tests and serum IgE tests were performed with inhalant and
food allergens, including molds and yeasts, 2 pasta sauces consumed by the
patient, individual sauce ingredients, and a food-quality yeast extract.
Radioallergosorbent test inhibition was used for specificity studies. RESULTS:
Skin prick and serum IgE test results were positive to several molds
(Cladosporium herbarum, Alternaria alternata, Aspergillus fumigatus, and
Penicillium notatum), baker's yeast (Saccharomyces cerevisiae), Malassezia
furfur, and champignon and to the 2 pasta sauces, the yeast ingredient, and a
food-quality yeast extract. Radioallergosorbent test inhibition studies confirmed
that the sauces contain cross-reacting yeast and mold allergens. CONCLUSIONS:
This patient has a clustered sensitization to fungi characterized by allergy to
environmental fungal allergens and to yeast extracts used in the food industry.
Yeasts should be considered as possible ingestive allergens in mold-allergic
patients.
PMID- 17042134
TI - Use of the health plan employer data and information set for measuring and
improving the quality of asthma care.
AB - OBJECTIVES: To discuss the Health Plan Employer Data and Information Set (HEDIS)
criteria for measuring performance in asthma care and to review new strategies to
improve the quality of asthma care. DATA SOURCES: Expert opinion from a
roundtable on National Committee for Quality Assurance HEDIS and asthma care,
supplemented with a MEDLINE database search to identify articles published
between January 1, 1990, and May 31, 2005, with the following keywords in the
title: asthma plus HEDIS, pay for performance, incentive programs, reimbursement,
or employee education. STUDY SELECTION: Studies and review articles were selected
for their relevance to measuring the quality of asthma care using HEDIS and
improving care using newer trends, such as employee education and physician
incentive programs. RESULTS: Components of the HEDIS asthma measure have been
found to correlate with outcomes, including risk of hospitalization and emergency
department visits. However, refinements to the measure may be needed because it
may misclassify a portion of patients as having persistent asthma who actually
have intermittent asthma according to National Heart, Lung, and Blood Institute
criteria. Physician incentive programs are increasingly being explored as a means
of improving the quality of care while managing costs. Under current pay-for
performance programs, rewards are issued to providers who demonstrate high
quality care based on the HEDIS asthma measure. CONCLUSIONS: The HEDIS asthma
measure remains the most widely used performance tool for evaluating the quality
of asthma care. Reimbursement models based on public reporting and pay for
performance are expected to be a strong component of future health care payment
systems.
PMID- 17042135
TI - Clinical and laboratory characteristics of 75 patients with specific
polysaccharide antibody deficiency syndrome.
AB - BACKGROUND: There are limited studies of large cohorts of patients with specific
polysaccharide antibody deficiency (SPAD) syndrome. OBJECTIVE: To study the
clinical and laboratory characteristics of patients with specific polysaccharide
antibody deficiency syndrome. METHODS: We retrospectively studied 75 patients
with total IgG levels of at least 500 mg/dL and fewer than 9 of 12 responses to
vaccination with pneumococcal vaccine polyvalent. Exclusion criteria included an
IgG level less than 500 mg/dL, established immunodeficiency syndrome, and
secondary immunodeficiency. RESULTS: The most common clinical presentation was
frequent infections (n = 69; 92%), including sinusitis (n = 53; 77%), pneumonia
(n = 29; 42%), ear infections (n = 18; 26%), and bronchitis (n = 19; 28%). Other
presentations were systemic infections (n = 5; 7%), autoimmune or rheumatic
diseases (n = 6; 8%), and chronic diarrhea (n = 4; 5%). The median IgG2 level of
patients with no response to pneumococcal vaccine polyvalent tended to be lower
than that of patients with at least 1 response (150 vs 193 mg/dL, respectively; P
= .06). There was no association between total IgG level (categorized as 500-600
or > or = 600 mg/dL) and frequency of infection (P = .43). Patients with fewer
responses to pneumococcal vaccine polyvalent and a higher frequency of infections
were more likely to receive intravenous immunoglobulin (IVIG) therapy (P = .01
and .003, respectively). Treatment with IVIG significantly reduced the number of
infections (P < .001). CONCLUSION: Patients with no response to pneumococcal
vaccine polyvalent tended to have lower IgG2 levels; those with fewer responses
were more likely to receive IVIG therapy.
PMID- 17042136
TI - Profiles of proinflammatory cytokines in sputum from different groups of severe
asthmatic patients.
AB - BACKGROUND: Severe asthma represents a heterogeneous group of patients whose
characteristics of airway inflammation are poorly known. OBJECTIVE: To evaluate
the sputum cytokine profiles of different phenotypes of severe asthma. METHODS:
Severe asthmatic patients (n = 45) were divided into 3 groups: frequent
exacerbations, persistent bronchoconstriction, and both features. Two other
groups (9 patients with untreated mild asthma and 10 control subjects) were also
studied. Selected sputum portions were assayed for differential cell count,
supernatant interleukin 5 (IL-5), granulocyte-macrophage colony-stimulating
factor, IL-8, and eosinophil cationic protein. RESULTS: There were no
statistically significant differences among the 3 severe asthma groups in terms
of sputum inflammatory cell percentages, IL-8 levels, and eosinophil cationic
protein levels, although IL-8 levels tended to be higher in patients with
persistent bronchoconstriction. Sputum concentrations of granulocyte-macrophage
colony-stimulating factor and IL-5 were significantly higher in patients with
frequent exacerbations compared with the other 2 groups. Levels of IL-5 and IL-8
were higher in severe asthmatic patients compared with mild asthmatic patients
and controls, whereas sputum eosinophil percentages were intermediate between
those of mild asthmatic patients and controls. CONCLUSIONS: Proeosinophilic
cytokine levels are increased in severe asthmatic patients with frequent
exacerbations but not in severe asthmatic patients with persistent
bronchoconstriction, suggesting that different cytokine profiles could be
associated with different phenotypes of severe asthma.
PMID- 17042137
TI - The effect of CD14-c159T genotypes on the cytokine response to endotoxin by
peripheral blood mononuclear cells from asthmatic children.
AB - BACKGROUND: A C-T polymorphism at position 159 in the promoter of CD14 (C-159T)
modulates the cellular response to endotoxin and significantly influences total
IgE levels. The effect of this genetic variant on the cytokine response of the
inflammatory cells is incompletely understood. OBJECTIVE: To investigate the
effects of CD14-C159T genotypes on the response to endotoxin by peripheral blood
mononuclear cells (PBMCs) in children with asthma. METHODS: The PBMCs from
asthmatic children with the TT (n = 11) and CC (n = 11) genotypes at the CD14
promoter were cultured in the presence of endotoxin, 100 ng/mL; concanavalin A,
10 microg/mL; or medium alone. Concentrations of soluble CD14 (sCD14),
interleukin (IL) 1beta, IL-4, IL-10, IL-12, IL-13, interferon-gamma, and
transforming growth factor beta were determined in culture supernatants by enzyme
linked immunosorbent assay, and the transcriptional differences were evaluated
using reverse-transcriptase polymerase chain reaction. RESULTS: Under
unstimulated conditions, children with the TT genotype produced higher levels of
sCD14 into the culture supernatant compared with children with the CC genotype (P
= .03, Mann Whitney U test). Both IL-10 and IL-1beta concentrations were
significantly higher in culture supernatants of children with the TT genotype
after endotoxin stimulation (P = .02 and P = .009, respectively, by analysis of
covariance [ANCOVA]). Messenger RNA expression was consistent with the results of
protein concentration for IL-10 and sCD14. Concanavalin A stimulation resulted in
lower levels of IL-4 in children with the TT genotype (P = .02, ANCOVA).
CONCLUSION: The genotype at the CD14 promoter C159T locus may significantly
influence the cytokine response of PBMCs obtained from asthmatic children.
Differences in IL-10 and IL-4 production by alternative genotypes may contribute
to the observed genotype effect on total IgE.
PMID- 17042138
TI - Effect of montelukast on bacterial sinusitis in allergic mice.
AB - BACKGROUND: In mice, allergic rhinitis augments the infectious and inflammatory
response to Streptococcus pneumoniae-induced sinusitis. OBJECTIVE: To investigate
the effects of cysteinyl leukotriene antagonism on the severity of bacterial
infection. METHODS: We performed 3 parallel, placebo-controlled experiments. In
the first, mice were ovalbumin sensitized and ovalbumin challenged to show the
effects of montelukast on the allergic inflammation; in the second, we evaluated
the effect of montelukast on S. pneumoniae infection; in the third, we used mice
that were both allergic and infected. Montelukast was given starting 2 days after
sensitization until the day before euthanasia. One day after drug treatment
began, the mice were inoculated intranasally with S. pneumoniae in the infected
groups. Nasal hypersensitivity was measured with histamine challenges before the
first sensitization and on the day before euthanasia. On the fifth day after
infection, mice were euthanized, nasal lavage was performed, bacteria were
cultured, and inflammatory cells in the sinuses were quantified. RESULTS: Mice
that were infected only tended toward having increased bacterial counts from
nasal lavage in the montelukast-treated group. The mice that were allergic and
infected experienced significantly higher bacterial counts (P < .05). All 3
montelukast treatment groups had significantly decreased eosinophil counts as
well as T-lymphocyte counts. CONCLUSIONS: Montelukast reduces the manifestations
of allergic rhinitis in mice. Surprisingly, montelukast led to an increase in
bacterial growth in infected mice. This suggests an effect of the cysteinyl
leukotrienes on the innate response to bacterial infection.
PMID- 17042140
TI - Allergenic proteins in Urtica dioica, a member of the Urticaceae allergenic
family.
AB - BACKGROUND: Allergy to the pollen of flowering plant species significantly
affects the health of people in many parts of the world. Pollens of related
genera usually share common antigens and are often, but not always, cross
reactive. Several studies have shown that Parietaria pollen is one of the most
common causes of pollinosis in the Mediterranean area, whereas Urtica has no
allergenic significance. OBJECTIVES: To report on the localization of Parietaria
judaica major allergen in Urtica dioica pollen grains and on the detection of
allergenic proteins in U. dioica pollen grains during the hydration-activation
process. METHODS: A combination of transmission electron microscopy and
immunocytochemical methods was used to locate allergenic proteins in U. dioica
pollen grains after different periods of hydration-activation using the anti-Par
j 1 (4.1.3.) monoclonal antibody and serum samples from allergic patients.
RESULTS: No significant labeling was noted for Parj 1 allergen after 10, 15, and
20 minutes in the walls and cytoplasm. Slight labeling was observed for allergic
proteins in the walls of U. dioica after 10 minutes of hydration, and no
significant labeling was found after 15 and 20 minutes of hydration. CONCLUSIONS:
Immunocytochemical methods confirmed the absence of cross-reactivity between 2
related genera, Parietaria and Urtica, and the lowest allergenic potential of U.
dioica.
PMID- 17042139
TI - Identification of italian cypress (Cupressus sempervirens) pollen allergen Cup s
3 using homology and cross-reactivity.
AB - BACKGROUND: The prevalence of seasonal allergic diseases of the upper airways is
increasing in industrialized countries. The Cupressaceae are important causes of
pollinosis, particularly in Europe. OBJECTIVE: To determine whether the pollen
from Cupressus sempervirens (Italian cypress) contains a pathogenesis-related
group 5 (PR-5) protein, similar to that found in other allergenic Cupressaceae
pollens. METHODS: Messenger RNA was purified from Italian cypress pollen, and
complementary DNA (cDNA) was synthesized. cDNAs for PR-5 proteins were amplified
by polymerase chain reaction and extended by rapid amplification of cDNA ends
methods. Recombinant Cup s 3 was expressed in Escherichia coli as a fusion
protein. Inhibition enzyme-linked immunosorbent assays were used to test the
allergenicity of Cup s 3. RESULTS: Three cDNAs were cloned. These clones had
approximately 95% identity to Jun a 3 and Cup a 3. Recombinant Cup s 3.0102
maltose-binding protein inhibited the IgE from most patients from binding to an
extract of Italian cypress. The extent of inhibition suggested that antibodies to
Cup s 3 were a prominent component of the IgE response to Italian cypress pollen.
CONCLUSION: Cup s 3, an allergen of Italian cypress pollen, was identified based
on cross-reactivity and homology with other pollen PR-5 proteins, despite an
apparently low level of protein expression. Variations in the content of Cup s 3
in the pollen from different regions or trees should be considered in the choice
of extracts for diagnosis and specific immunotherapy for Italian cypress pollen
hypersensitivity.
PMID- 17042141
TI - Comparison of enzyme immunoassay-based assays for environmental Alternaria
alternata.
AB - BACKGROUND: Alternaria alternata-derived allergenic materials are causes of human
disease. Several immunoassays exist to quantify these materials. OBJECTIVE: To
compare methods for evaluating Alternaria content. METHODS: Four methods,
including 1 monoclonal antibody (MAb)-based assay specific for recombinant Alt a
1, 1 MAb-based assay for chromatographically purified Alt a 1, 1 polyclonal
antibody (PAb)-based assay for chromatographically purified Alt a 1, and 1 PAb
based assay for whole Alternaria extract, were evaluated. Environmental samples
collected as part of the National Survey of Lead and Allergens in Housing were
examined. Alternaria spore counts were determined in dust by observation.
RESULTS: The MAb-based assay for recombinant Alt a 1 detected Alternaria in few
samples (25%); the PAb-based assay for whole Alternaria proteins detected antigen
in 97% of the samples. The PAb- and MAb-based assays for purified Alt a 1
detected antigen in 100% of the samples. There was a significant positive
correlation between the 2 assays directed against purified Alt a 1. There was a
positive correlation between the PAb-based assay for whole Alternaria and the PAb
based assay for Alt a 1. Nearly all the dust samples contained Alternaria spores,
and there was a strong positive correlation between counts and all assays.
CONCLUSION: Because of the multifaceted nature of Alternaria, the disparities
between methods for quantifying Alternaria, the cross-reactivity between fungal
allergens, and the documented genetic promiscuity of this fungus, enzyme
immunoassays using PAbs against a range of Alternaria proteins will probably
produce the most reliable estimation of overall Alternaria exposure in house
dust.
PMID- 17042143
TI - Use of complementary and alternative medicine by food-allergic patients.
AB - BACKGROUND: Interest in complementary and alternative medicine (CAM) is
increasing. Use of CAM in food-allergic patients has not previously been
evaluated. OBJECTIVES: To determine the prevalence of CAM use, the types of CAM
modalities used, and opinions about CAM in food-allergic patients. METHODS: A
questionnaire was distributed to attendees at a patient conference in 2002 and to
patients at pediatric food allergy clinics in 2005. RESULTS: Surveys were
completed by 380 families. Respondents were mainly white, parents of children
with multiple food allergies, and from the tri-state (New York, New Jersey,
Connecticut) area. Diagnostic modalities considered unproven or disproven (such
as serum IgG4, electrodermal skin testing, and kinesiology) were used by 22% of
respondents; CAM therapies were used by 18%. Participants used several types of
CAM practitioners, the most common being chiropractors, homeopaths, and
acupuncturists. Only 49% of patients using CAM disclosed this to their
physicians. Efficacy ratings for CAM were poor. Regarding participants' opinions,
an herbal therapy of equal efficacy, safety, and cost was preferred to a
pharmaceutical drug (37% vs 12%; P = .001), but most participants (51%) had no
preference or were unsure. CONCLUSION: Unproven or disproven diagnostic methods
and CAM treatments were used by approximately 1 in 5 respondents. Those using CAM
noted poor efficacy, but if given a choice, many would prefer herbal therapies to
pharmaceutical drugs. Education regarding reliable testing for food allergy and
further research on CAM therapies are warranted.
PMID- 17042142
TI - Evaluation of antibody binding to diisocyanate protein conjugates in a general
population.
AB - BACKGROUND: Specific IgG binding to diisocyanate-human serum albumin (HSA) has
been proposed as an indicator of diisocyanate exposure. One residential study
reported IgG binding to diisocyanate conjugates in 8% of residents living near a
factory using toluene diisocyanate (TDI). Because comparable assays were not
performed using individuals distant from such facilities, the significance of
this finding is uncertain. OBJECTIVE: To determine the prevalence of diisocyanate
specific antibodies in sera from individuals "not known to be exposed" to
diisocyanates. METHODS: Serum samples from 139 anonymous donors without known
diisocyanate exposure were assayed by means of enzyme-linked immunosorbent assay
for IgG or IgE specific for TDI-HSA, diphenylmethane diisocyanate (MOI)-HSA, and
hexamethylene diisocyanate (HDI)-HSA. Positive responses (optical density > or =
0.1 and > or = 3 SDs above the mean of 8 laboratory controls) were run 3 times.
Competitive inhibition was performed for sera exhibiting binding of optical
density of at least 0.2. RESULTS: We detected IgG reactive with HDI-HSA,
diphenylmethane diisocyanate-HSA, and TDI-HSA in 18 (13%), 0, and 7 donors (5%),
respectively. Inhibition (>50%) was demonstrated in 6 of 9 participants with
elevated HDI-HSA levels and in 2 of 7 with elevated TDI-HSA levels. We detected
IgE reactive with the same antigens in 3 donors (2%); however, none were
confirmed to be positive using the biotin-streptavidin IgE assay. CONCLUSIONS:
Specific and nonspecific IgG binding to HDI-HSA and TDI-HSA were detected in
individuals without known exposure to isocyanates. These antibody measurements
may not be reliable indicators of diisocyanate exposure in nonoccupational
populations and should not be interpreted as surrogates of diisocyanate exposure
in the absence of defined referent populations.
PMID- 17042144
TI - Fasting: an important issue in asthma management compliance.
AB - BACKGROUND: Fasting, neither eating nor drinking anything between dawn (sahur
time) and sundown (iftar time), may have an important role in the treatment and
follow-up of asthmatic patients in countries where most of the population is
Muslim. OBJECTIVE: To analyze the effects of fasting on outpatient asthmatic
patients. METHODS: One hundred twenty-one fasting patients were evaluated for
attendance at follow-up visits, attitudes about undergoing diagnostic
investigations, and opinions and practices regarding medication use during
fasting. Their sources of knowledge about asthma, fasting, and medication
consumption were also evaluated. RESULTS: Ninety percent of fasting patients
reported no harm with respect to religion of visiting physicians while fasting.
Although 96% of the patients stated that inhaled medication could be used, only
13% continued to use medication in the same manner as when they were not fasting.
Most patients rearranged their medication-consumption hours. Although 96% of the
patients received general information about asthma from their physicians, rates
of receiving information about the fasting-medication use relationship from
physicians and religious sources were similar (37% and 32%, respectively).
CONCLUSION: Most Muslim asthmatic patients do not consider asthma to be a
drawback to fasting, and they continue fasting by rearranging their medication
consumption times. During Ramadan, patients should be questioned about this
subject and should be followed up carefully for asthma control at regular visits.
PMID- 17042145
TI - Impact of azelastine nasal spray on symptoms and quality of life compared with
cetirizine oral tablets in patients with seasonal allergic rhinitis.
AB - BACKGROUND: In fall 2004, the first Azelastine Cetirizine Trial demonstrated
statistically significant improvements in the total nasal symptom score (TNSS)
and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores with the use
of azelastine nasal spray vs oral cetirizine in patients with seasonal allergic
rhinitis (SAR). OBJECTIVE: To compare the effects of azelastine nasal spray vs
cetirizine on the TNSS and RQLQ scores in patients with SAR. METHODS: This 2
week, double-blind, multicenter trial randomized 360 patients with moderate-to
severe SAR to azelastine, 2 sprays per nostril twice daily, or cetirizine, 10-mg
tablets once daily. The primary efficacy variable was the 12-hour reflective TNSS
(rhinorrhea, sneezing, itchy nose, and nasal congestion). Secondary efficacy
variables were individual symptom scores and the RQLQ score. RESULTS: Azelastine
nasal spray and cetirizine significantly improved the TNSS and individual
symptoms compared with baseline (P < .001). The TNSS improved by a mean of 4.6
(23.9%) with azelastine nasal spray compared with 3.9 (19.6%) with cetirizine.
Significant differences favoring azelastine nasal spray were seen for the
individual symptoms of sneezing and nasal congestion. Improvements in the RQLQ
overall (P = .002) and individual domain (P < or = .02) scores were greater with
azelastine nasal spray. Both treatments were well tolerated. CONCLUSIONS:
Azelastine nasal spray and cetirizine effectively treated nasal symptoms in
patients with SAR. Improvements in the TNSS and individual symptoms favored
azelastine over cetirizine, with significant differences for nasal congestion and
sneezing. Azelastine nasal spray significantly improved the RQLQ overall and
domain scores compared with cetirizine.
PMID- 17042146
TI - Effect of formoterol fumarate treatment on exercise-induced bronchoconstriction
in children.
AB - BACKGROUND: Exercise-induced bronchoconstriction (EIB) is common, particularly in
children. OBJECTIVES: To compare the protective effect of single doses of
formoterol fumarate via Aerolizer with placebo and albuterol in children with
EIB. METHODS: In this randomized, double-blind, double-dummy, crossover trial, 23
children (aged 4-11 years) received formoterol, 12 or 24 microg; albuterol, 180
microg; or placebo at 4 separate visits. Protection against EIB was evaluated as
the maximum percentage decrease in forced expiratory volume in 1 second (FEV1)
from the preexercise value after exercise challenge tests (6-minute treadmill)
conducted 15 minutes and 4, 8, and 12 hours after administration of the dose.
RESULTS: The maximum percentage decrease in FEV1 after the 4-hour exercise test
(primary efficacy variable) was significantly less for formoterol, 12 and 24
microg, vs placebo (P < .001 for both) or albuterol (P = .016 and .010,
respectively); albuterol was not significantly different from placebo.
Formoterol, 12 and 24 microg, differed from placebo at 8 hours (P = .002 and
.001, respectively), with a smaller difference between albuterol and placebo (P =
.045). Rescue medication use and a high dropout rate may have biased treatment
differences at later time points. Protection against EIB (<20% maximum decrease
in FEV1) across all time points was observed for 17 (77%) of 22 and 17 (74%) of
23 children with formoterol, 12 and 24 microg, respectively, compared with 8
(35%) of 23 with albuterol and 6 (27%) of 22 with placebo. CONCLUSIONS: Single
doses of formoterol, 12 or 24 microg, are effective in protecting against EIB in
children, affording a statistically significantly greater protective effect than
placebo or albuterol.
PMID- 17042147
TI - Comparison of cetirizine-pseudoephedrine and placebo in patients with seasonal
allergic rhinitis and concomitant mild-to-moderate asthma: randomized, double
blind study.
AB - BACKGROUND: Allergic rhinitis (AR) and asthma are common concurrent conditions.
OBJECTIVES: To evaluate the effects of cetirizine hydrochloride (5 mg)
pseudoephedrine hydrochloride (120 mg) (cetirizine-D) twice daily on AR and
asthma symptoms, pulmonary function, and asthma-related quality of life in 274
patients with confirmed seasonal AR and concomitant mild-to-moderate asthma.
METHODS: In this multicenter, randomized, double-blind, placebo-controlled study,
after a 1-week screening period, patients took cetirizine-D or placebo for 4
weeks. The primary efficacy variable, AR total symptom severity complex score,
was derived from patient daily diary ratings of sneezing, runny nose, itchy nose,
postnasal drip, and nasal congestion. Asthma symptom severity total scores were
derived from twice-daily diary ratings of wheezing, coughing, shortness of
breath, and chest tightness. Pulmonary function was tested at clinic visits and
by patients each morning and evening. Patients completed the Asthma Quality of
Life Questionnaire at each visit. All tests were 2-sided, with statistical
significance at the .05 level. RESULTS: Cetirizine-D reduced total symptom
severity complex scores by 42.3% overall vs 23.6% with placebo (P < .001). Asthma
symptom severity total scores were significantly improved with cetirizine-D at
most times vs placebo. Cetirizine-D treatment was also associated with
significantly improved Asthma Quality of Life Questionnaire overall scores.
Pulmonary function test results were neutral. Cetirizine-D was well tolerated,
with discontinuation and adverse event rates similar to placebo. Somnolence
occurred in 8 patients (5.8%) taking cetirizine-D and in 1 (0.7%) taking placebo.
CONCLUSIONS: Treatment with cetirizine-D twice daily significantly reduced
rhinitis and asthma symptoms and improved overall asthma quality of life in
patients with seasonal AR and concomitant mild-to-moderate asthma.
PMID- 17042149
TI - Medication compliance and disease exacerbation in patients with asthma: a
retrospective study of managed care data.
AB - BACKGROUND: Compliance with asthma medications probably results in improved
outcomes, but few studies have examined this relationship. OBJECTIVE: To examine
the association between medication compliance and exacerbation in asthmatic
patients. METHODS: Retrospective analysis of a managed care database. The 97,743
participants (aged 6-99 years; mean age, 32.8 years) had asthma and prescriptions
for controller medications. Compliance with the index medication (the first
controller medication prescribed) was measured using 2 methods: medication
possession ratio (MPR), calculated for 365 days after the index date, and number
of prescriptions for each index medication. Exacerbation was defined as 1 or more
emergency department visits or hospitalizations within 1 year of the index date.
Multivariate models were used to determine the odds of exacerbation based on
relative compliance for each definition of compliance. RESULTS: Based on the
median MPR, more-compliant patients were less likely to experience exacerbation
than less-compliant patients (odds ratio, 0.94; 95% confidence interval, 0.91
0.97; P < .001). Using the 75th percentile MPR, risk of exacerbation was even
smaller (odds ratio, 0.89; 95% confidence interval, 0.86-0.92; P < .001). All the
cutoff points for compliance (> or = 2 through > or = 6 prescriptions)
demonstrated significantly less exacerbations in more-compliant vs less-compliant
patients after adjusting for covariates. As the criteria for compliance became
more stringent, more-compliant patients became increasingly less likely to have
an exacerbation vs less-compliant patients. CONCLUSION: More-compliant asthmatic
patients were significantly less likely to experience exacerbation than less
compliant asthmatic patients. These findings demonstrate the importance of
improving medication compliance among asthmatic patients to impact outcomes.
PMID- 17042148
TI - Treatment with 400 microg of inhaled budesonide vs 200 microg of inhaled
budesonide and oral montelukast in children with moderate persistent asthma:
randomized controlled trial.
AB - BACKGROUND: Montelukast is reported to be beneficial in asthma as add-on therapy
to inhaled corticosteroids and may reduce the need for the latter. OBJECTIVE: To
evaluate whether a combination of oral montelukast and 200 microg of inhaled
budesonide has comparable efficacy to 400 microg of inhaled budesonide alone in
children with moderate persistent asthma. METHODS: In this prospective, blinded,
hospital-based randomized controlled trial, 71 children with moderate persistent
asthma were randomized to receive either montelukast, 5-mg chewable tablet, with
200 microg of inhaled budesonide or only 400 microg of inhaled budesonide daily
for 12 weeks. Baseline and serial measurements of forced expiratory volume in 1
second, peak expiratory flow rate, and Asthma Symptom Score were performed; the
frequency and severity of exacerbations were also recorded. RESULTS: Measurements
of forced expiratory volume in 1 second, peak expiratory flow rate, and Asthma
Symptom Score showed no significant differences between the 2 groups at baseline,
during the serial follow-up visits, and at the end of the study. However,
children who received montelukast had a greater frequency of exacerbations vs
those who did not (33.3% vs 9.1%; P < .01). CONCLUSION: The overall control of
asthma with 5 mg of oral montelukast and 200 microg of inhaled budesonide is
inferior to that with 400 microg of inhaled budesonide in children with moderate
persistent asthma.
PMID- 17042151
TI - Empowering patients with a history of anaphylaxis to use an epinephrine
autoinjector without fear.
PMID- 17042150
TI - Asthma-related health status determinants of environmental control practices for
inner-city preschool children.
AB - BACKGROUND: Asthma guidelines recommend environmental control practices (ECPs) to
improve asthma health. In the inner city, where asthma morbidity is high, it is
not known whether children's health status affects the use of ECPs. OBJECTIVE: To
investigate health status determinants of ECPs in the homes of children with
asthma. METHODS: Caregivers of children aged 2 to 6 years with (n = 150) and
without (n = 150) asthma completed a survey about ECPs. Atopic status was
determined by means of skin prick testing. RESULTS: Most ECPs were similarly
practiced, regardless of whether the child had asthma. Only pet avoidance was
more common in children with asthma (30% vs 19%). Asthma severity and recent
acute health care visits for asthma were not associated with ECP use. Most ECPs
were not linked to allergen sensitization (eg, mite and mouse), although
cockroach-sensitized children were more likely to have cockroach control than
nonsensitized individuals (65% vs 45%). Caregivers of asthmatic children with
rhinitis were more likely than those without rhinitis to report ECPs, including
pet avoidance (44% vs 15%), smoking avoidance (78% vs 53%), cockroach control
(65% vs 42%), mouse control (78% vs 42%), air-conditioning (45% vs 24%), and
allergyproof covers (7% vs 0%). CONCLUSIONS: The presence of asthma, asthma
severity, and allergen sensitization seem to have little relationship to ECP use
in the homes of inner-city children. Rhinitis was consistently linked to ECPs,
which suggests that caregivers may make changes in the home environment for upper
airway but not lower airway symptoms.
PMID- 17042152
TI - Guideline 1: minimum technical requirements for performing clinical
electroencephalography.
PMID- 17042153
TI - Guideline two: minimum technical standards for pediatric electroencephalography.
PMID- 17042154
TI - Guideline 3: minimum technical standards for EEG recording in suspected cerebral
death.
PMID- 17042155
TI - Guideline 4: standards of practice in clinical electroencephalography.
PMID- 17042156
TI - Guideline 5: guidelines for standard electrode position nomenclature.
PMID- 17042157
TI - Guideline 6: a proposal for standard montages to be used in clinical EEG.
PMID- 17042158
TI - Guideline 7: guidelines for writing EEG reports.
PMID- 17042159
TI - Guideline 8: guidelines for recording clinical EEG on digital media.
PMID- 17042160
TI - Guideline 9A: guidelines on evoked potentials.
PMID- 17042161
TI - Guideline 9B: guidelines on visual evoked potentials.
PMID- 17042163
TI - Guideline 9D: guidelines on short-latency somatosensory evoked potentials.
PMID- 17042162
TI - Guideline 9C: guidelines on short-latency auditory evoked potentials.
PMID- 17042164
TI - Guideline 10: guidelines for writing clinical evoked potential reports.
PMID- 17042165
TI - Immunization against periodontal disease: current strategy and future prospects.
PMID- 17042166
TI - Association of periodontal disease severity with diabetes duration and diabetic
complications in patients with type 1 diabetes mellitus.
AB - OBJECTIVES: The association between periodontal disease severity and diabetes
complications and duration in patients with type 1 diabetes mellitus (DM) was
investigated in this comparative cross-sectional study. MATERIALS AND METHODS:
Twenty-nine patients with type 1 DM of < or = 5 years duration were compared with
43 patients with > 5 years duration of DM. Complete medical history and
examination and assessments of retinopathy, neuropathy, and nephropathy were
performed, followed by assessments of the plaque index (PI), pocket depth (PD),
clinical attachment level (CAL), and the number of missing teeth by one examiner
masked to the diabetic status of the patients. RESULTS: The number of missing
teeth (4 versus 0) and CAL (2.88 vs 2.56 mm) were significantly higher in
patients with longer DM duration (p < 0.05). For patients with > or = 5 years DM
duration, periodontal disease severity was also greater in patients with one or
more DM complications, as assessed by the number of missing teeth (17 vs 0; p <
0.001) and CAL (4.74 vs 2.81 mm; p < 0.01). Stepwise multiple regression analysis
associated the presence of > or = 1 DM complications and smoking history with
severe attachment loss (CAL > or = 7 mm; p < 0.001). CONCLUSION: Periodontal
disease severity is associated with both DM duration and the presence of DM
complications in this sample of type 1 DM patients.
PMID- 17042167
TI - SEM analyses of bacterial contamination of e-PTFE membranes and GTR clinical
results.
AB - The aim of the present study was to determine whether bacterial contamination of
expanded polytetrafluoroethylene (e-PTFE) membranes and the degree of membrane
exposure could affect the clinical results of guided tissue regeneration (GTR).
Seven patients (aged 42 to 58 years) presented with twenty intrabony defects that
were treated by GTR + DFDBA (decalcified freeze-dried bone allograft). Gingival
recession, probing depths, and clinical attachment levels were recorded before
surgery and 10 months subsequently. Exposure of the membrane was recorded at the
moment of removal. The membranes were analyzed in three distinct regions by
scanning electron microscopy (SEM): collar, medial and apical regions. The
presence of host cells adhering to the e-PTFE membrane was determined and
bacterial contamination was quantified as per Simion et al. (1994). Statistical
analysis did not show significant differences for bacterial contamination or for
the presence of host cells on the membrane surface at different levels of
exposure (up to 30%, from 31% to 60%, and from 61% to 75%). Results were
considered statistically significant at p < 0.05, according to the Kruskal-Wallis
rank sum test. Exposure of the membrane and bacterial contamination did not
modify the levels recorded. Bacterial contamination had an adverse effect on bone
defect filling.
PMID- 17042168
TI - Repeated oral hygiene instructions alone, or in combination with metronidazole
dental gel with or without subgingival scaling in adult periodontitis patients: a
one-year clinical study.
AB - The aims of the present study were to evaluate the clinical efficacy of, and to
monitor microbiologically, repeated oral hygiene instructions alone or in
combination with metronidazole 25% gel or subgingival scaling with or without
metronidazole gel in treatment of new, residual or recurrent periodontal pockets
in previously treated adult periodontitis patients. Ten suitable patients were
included in this randomized single-blind clinical study with an intra-individual
design. Clinical parameters were measured before and at 1, 3, 6, 9 and 12 months
after treatment. Subgingival plaque samples were taken at every examination from
one selected site in each quadrant. Smears from plaque samples were silver
stained and differential counting was performed under light microscopy at 1000X
magnification. Four treatment modalities: (i) oral hygiene instruction (OHI)
alone; (ii) OHI and metronidazole dental gel; (iii) OHI and subgingival scaling;
(iv) OHI and subgingival scaling plus metronidazole gel, were randomly assigned
to one quadrant of each patient. At the 12-month examination, the mean reductions
in probing pocket depth were 2.6 mm after OHI alone, 2.8 mm after OHI and
metronidazole gel, 3.3 mm after OHI and subgingival scaling and 2.6 mm after oral
OHI and subgingival scaling plus metronidazole gel. The mean gains in probing
attachment level were 2.2 mm, 1.9 mm, 2.7 mm and 1.6 mm, respectively. Although
there were statistically significant differences in treatment responses between
some treatment modalities at some time points, these were not considered to be
clinically significant. Differential counts showed a shift towards a healthy
microflora in response to all treatment modalities. From the 12-month results, it
was concluded that the metronidazole 25% gel produced positive effects on the
clinical parameters and on the subgingival plaque microbiological composition in
new, residual or recurrent pockets in previously treated chronic periodontitis
patients. However, the metronidazole gel alone or in combination with scaling
does not seem to have any additional clinically significant therapeutic effects
over and above those derived from improved oral hygiene resulting from monthly
recalls, with or without subgingival scaling.
PMID- 17042169
TI - Periodontal diseases in Asians.
AB - Asia encompasses three of the four most populous nations in the world (China,
India and Indonesia), accounting for nearly two-fifths of the worlds' total
population. Over half of the world's population now inhabits Asia, which by
definition includes countries of the Middle East and some former Socialist Soviet
Republics. There has been a generally held view that Asians are particularly
susceptible to periodontitis. The aim of this review is to consider the reasons
for this view having become entrenched and to examine the evidence on which it
could have been established and sustained. This view of a particularly high
prevalence of periodontal diseases in Asians appears in retrospect to have
originated from early epidemiological studies using an index system which gives
weight to gingivitis and moderate periodontitis resulting from poor oral hygiene
and calculus deposition, very commonly encountered in Asian populations. Studies
that have been conducted comparing Asians immigrants with native Caucasians in
industrialized northern hemisphere nations broadly concluded that Asians
displayed worse periodontal conditions than Caucasians. Similarly, a classic
study comparing Norwegian males with Sri Lankan Tamil males demonstrated worse
periodontal conditions in the Asian males. A recent review (Albander and Rams,
2002) has stated that those of African origin display the highest prevalence of
periodontitis followed by Hispanics and Asians. Studies of the natural history of
periodontal disease in Asians, of perio-dontopathogens in Asians, of risk for
periodontal destruction, and of reasons for extraction do not appear to explain
increased susceptibility of Asians to periodontal destruction. Poor oral hygiene
and calculus deposits are widespread, however. Traditional assessments of
periodontitis focus on destruction of the periodontal attachment in terms of
attachment loss and probing pocket depths, with no consideration being given to
the morphological features of the dentition from which the periodontal attachment
is being lost, features that may predispose to or complicate the management of
periodontal destruction. The Mongoloid dentition shows a high prevalence of such
features, which adds a further dimension to the consideration of periodontal
diseases among many Asian peoples. Appropriate strategies for the prevention and
management of periodontal disease should focus upon improvements in the oral
hygiene situation in the diverse continent of Asia.
PMID- 17042170
TI - Determination of monensin, narasin, and salinomycin in mineral premixes,
supplements, and animal feeds by liquid chromatography and post-column
derivatization: collaborative study.
AB - A liquid chromatographic (LC) method for the analysis of monensin, narasin, and
salinomycin in mineral premixes, supplements, and complete animal feeds at
medicating and trace levels was collaboratively studied. The method uses methanol
water (90 + 10) extraction with mechanical shaking for 1 h, filtration, and
dilution if necessary. Determination of the 3 ionophores is by reversed-phase LC
using post-column derivatization with vanillin and detection at 520 nm. Suspect
positive trace-level products and medicated feeds containing unexpected
ionophores are confirmed by hexane extraction or post-column derivatization with
dimethylaminobenzaldehyde (DMAB). Twenty-five test samples of medicated feeds,
supplements, and mineral and drug premixes, and 9 test samples for trace-level
analysis were sent to 11 collaborators in Bulgaria, Czech Republic, Portugal,
France, The Netherlands, United States, and Canada. Acceptable results were
received from 10 laboratories. For the medicated complete feeds, supplements, and
mineral premixes, RSDr values (within-laboratory repeatability) ranged from 2.5
to 5.2%, RSDR values (among-laboratory reproducibility) ranged from 2.7 to 6.8%,
and HorRat values ranged from 0.31 to 1.30. For the drug premixes, the result
variability was excessive and HorRat values ranged from 2.27 to 14.1. For the
trace-level test samples, all laboratories correctly identified the analytes and
did not report any false positives. RSDr values ranged from 1.3 to 9.5%, RSDR
values ranged from 5.2 to 13.1%, and HorRat values ranged from 0.4 to 0.97.
PMID- 17042171
TI - Ion chromatographic determination of phosphorus soluble in different extracting
media in fertilizers.
AB - A new method based on ion chromatography (IC) was developed for the determination
of phosphorus in fertilizers. Fertilizers were extracted with water, mineral
acids, and 2% formic acid, 2% citric acid, and neutral ammonium citrate solutions
according to European Regulation No. 2003/2003 of the European Parliament and the
Council of October 13, 2003, or the Decree of the Italian Agriculture Minister of
June 17, 2002; the extracts were analyzed by direct injection, after simple
filtration, by IC on an IonPac AS19 (250 x 4 mm id) column, using a KOH (21-50-21
mM) gradient and suppressed conductivity detection. The calibration plot was
linear over the range of 5-50 mg/L (r(2) of >0.999). The method was evaluated by
comparison with a gravimetric method according to established norms. Associated
uncertainty at the 95% confidence level was established as 0.47% for the
determination of 3-46% P2O5 by IC. A good chromatographic separation of
phosphorus forms such as phosphates and phosphites, and some other important
anions like nitrates, chlorides, and sulfates present in many commercial
fertilizers was also possible, with a linear response over the range of 5-50
mg/L. After a more complete validation, this IC determination of phosphorus could
replace more tedious methods such as those using gravimetric determinations.
PMID- 17042172
TI - Affinity liquid chromatography method for the quantification of immunoglobulin G
in bovine colostrum powders.
AB - An affinity liquid chromatography (LC) method for the determination of bovine
immunoglobulin G (IgG), using protein G coupled to an agarose support, was
modified to permit the quantification of IgG in colostrum-based powders. Sample
preparation included pH adjustment to 4.6 to precipitate casein and denatured
whey protein. The method was applied to a range of colostrum powders and was
compared with the alternative independent methods of surface plasmon resonance
immunoassay, radial immunodiffusion, and reversed-phase LC. The method was rapid,
and performance parameters included a working range of 10-150 microg IgG and
precision relative standard deviation values of <10%.
PMID- 17042173
TI - Direct determination of lycopene content in tomatoes (Lycopersicon esculentum) by
attenuated total reflectance infrared spectroscopy and multivariate analysis.
AB - Lycopene is a potent antioxidant that has been shown to play critical roles in
disease prevention. Efficient assays for detection and quantification of lycopene
are desirable as alternatives to time- and labor-intensive methods. Attenuated
total reflectance infrared (ATR-IR) spectroscopy was used for quantification of
lycopene in tomato varieties. Calibration models were developed by partial least
squares regression (PLSR) using quantitative measures of lycopene concentration
from liquid chromatography as reference method. IR spectra showed a distinct
marker band at 957 cm(-1) for trans Carbon-Hydrogen (CH) deformation vibration of
lycopene. PLSR models predicted the lycopene content accurately and reproducibly
with a correlation coefficient (sigma) of 0.96 and standard error of cross
validation <0.80 mg/100 g. ATR-IR spectroscopy allowed for rapid, simple, and
accurate determination of lycopene in tomatoes with minimal sample preparation.
Results suggest that the ATR-IR method is applicable for high-throughput
quantitative analysis and screening for lycopene in tomatoes.
PMID- 17042174
TI - Highly sensitive spectrofluorimetric determination of ephedrine hydrochloride in
pharmaceutical preparations.
AB - A sensitive and specific spectrofluorimetry method was developed and validated
for the quantification of ephedrine (EP) in pharmaceutical preparations. The
method is based on the fluorescent enhancing reaction of EP with 7-chloro-4
nitrobenzofurazan (NBD-C1; derivatization reagent), in borate buffer of pH 9 to
yield a yellow, fluorescent product. Under these experimental conditions, the
derivatized product of EP had excitation and emission wavelength maxima at 458
and 516 nm, respectively. The linear range of this method was 20-2500 ng/mL. The
detection limit was 7.3 ng/mL EP. Intra- and interday precisions of the assay at
3 concentrations within this range were 0.037-1.77%. The low relative standard
deviation values indicate good precision, and high recovery values indicate
excellent accuracy of the method. The proposed method was applied to the
determination of the examined drugs in pharmaceutical formulations, and the
results indicate that the method is equally as accurate, precise, and
reproducible as the official method.
PMID- 17042175
TI - Validation of liquid chromatography and liquid chromatography/tandem mass
spectrometry methods for the determination of etoricoxib in pharmaceutical
formulations.
AB - Reversed-phase liquid chromatography (LC) and LC/tandem mass spectrometry
(LC/MS/MS) methods were developed and validated for the determination of
etoricoxib in pharmaceutical dosage forms. The LC method was performed by
reversed-phase chromatography on a Synergi fusion C18 column (150 x 4.6 mm id)
maintained at ambient temperature. The mobile phase consisted of 0.01 M
phosphoric acid, pH 3.0-acetonitrile (62 + 38, v/v) at a flow rate of 1.0 mL/min,
and photodiode array detection at 234 nm was used. The chromatographic separation
was obtained within 7.0 min, and calibration curves were linear in the
concentration range of 0.02-150 microg/mL. The LC/MS/MS method was performed on a
Luna C18 column (50 x 3.0 mm id). The mobile phase consisted of acetonitrile
water (95 + 5)-0.1% acetic acid (90 + 10, v/v). Detection was performed by
positive electrospray ionization in the multiple reaction monitoring mode,
monitoring the transitions 359.3 > 280.0 and 332.0 > 95.0 for etoricoxib and
piroxicam (internal standard), respectively. The chromatographic separation was
obtained within 2.0 min, and calibration curves were linear in the concentration
range of 1-5000 ng/mL. Validation parameters, such as specificity, linearity,
precision, accuracy, and robustness, were evaluated, which gave results within
the acceptable range for both methods. Moreover, the proposed methods were
successfully applied for routine quality control analysis of pharmaceutical
products and showed significant correlation (r = 0.9999) of the results.
PMID- 17042176
TI - A validated spectrofluorometric assay for the determination of certain macrolide
antibiotics in pharmaceutical formulations and spiked biological fluids.
AB - This paper describes a simple spectrofluorometric method for the analysis of 4
macrolide antibiotics. The method is based on the condensation of 10% (w/v)
malonic acid and acetic acid anhydride under the catalytic effect of tertiary
amine groups of the studied macrolides. The relative fluorescence intensity of
the condensation product was measured at 397/452 nm (excitation/emission) for
azithromycin dihydrate and at 392/445 nm (for clarithromycin, erythromycin
ethylsuccinate, and roxithromycin. All variables affecting the reaction
conditions were studied. The effects of potential interference due to common
excipients, such as starch, lactose, sucrose, glucose, gum acacia, and magnesium
stearate, as well as trimethoprim and sulfisoxazole acetyl formulated in
primomycin capsules and pediazole oral suspension, respectively, were studied. A
validation study for the proposed method was carried out according to U.S.
Pharmacopeia 2002. The linearity ranges were 3-80 ng/mL for all of the cited
macrolides. The limit of detection range was 0.74-1.20 ng/mL, while the limit of
quantitation range was 2.47-4.02 ng/mL. The method was applied for the assay of
the studied macrolides in pure pharmaceutical formulations and in spiked
biological fluids. Results were compared with those obtained from the reported
method, where calculated t- and F-values indicated high accuracy and good
precision for the proposed method.
PMID- 17042177
TI - Spectrofluorometric determination of citalopram in pharmaceutical preparations
and spiked human plasma using organized media.
AB - The native fluorescence of citalopram (CIT) was obtained in citrate buffer of pH
6.5 with and without beta-cyclodextrin (beta-CD) or sodium dodecyl sulfate (SDS)
as fluorescence enhancers at 305 nm using 242 nm for excitation. Micellar systems
of ionic and nonionic surfactants were investigated by measuring the fluorescence
intensity of the analyte-surfactant system. In slightly acidic aqueous solution
of pH 6.5, CIT was better incorporated in CDs and SDS micelles. The luminescence
emission from CIT was found to be greatly enhanced by SDS micelles. The
fluorescence intensity enhancements in CDs medium and in SDS as ionic surfactant
relative to slightly acidic aqueous solution were 125 and 250%, respectively.
Organized media-enhanced spectroflourometric methods were developed for the
determination of CIT, in pure form as well as in pharmaceutical preparations. The
fluorescence intensity-concentration plots were rectilinear over the ranges 0.06
to 0.64, 0.04 to 0.40, and 0.02 to 0.26 microg/mL with lower detection limits of
0.02, 0.01, and 0.007 microg/mL, either in citrate buffer only or in beta-CD and
SDS as organized media, respectively. Furthermore, the high sensitivity attained
by using SDS as organized medium allowed in vitro spectrofluorometric
determination of CIT in spiked human plasma. Interference from endogenous amino
acids has been overcome by using the solid-phase extraction technique; the mean
recovery (n = 5) was 100.1+/-0.8%
PMID- 17042178
TI - First-derivative spectrophotometry in the analysis of rosiglitazone in coated
tablets.
AB - First-derivative spectrophotometry, applying the peak-zero method, was developed
for the determination of rosiglitazone (RSG) in coated tablets. The solutions of
standard and sample were prepared in ethanol. Quantitative determination of the
drug was performed at 331.4 nm (N = 4; delta lambda = 3.2 nm) and was evaluated
for the parameters specificity, linearity, precision, and accuracy. The
specificity test showed that there was no interference from excipients commonly
found in the commercial pharmaceutical formulation at 331.4 nm. The standard
curve showed a correlation coefficient of 0.9997. Precision was demonstrated by a
relative standard deviation value of 0.50%. The recovery test resulted in an
average of 100.06%, which confirmed the accuracy of the method. The results for
first-derivative spectrophotometry (D(1)), liquid chromatography, and micellar
electrokinetic chromatography were compared by analysis of variance (ANOVA), and
there were no significant differences among these methods. Therefore, D(1) can be
easily and directly applied to analyze RSG in coated tablets.
PMID- 17042179
TI - Proficiency testing as a tool to assess the performance of visual TLC
quantitation estimates.
AB - The use of rapid and inexpensive nonlaboratory-based screening tests for drug
quality assessments is recommended as a component of a drug quality assurance
program in poor resource settings. We have established routine Minilab test
procedures to screen product quality and a proficiency testing program to
determine the competency of the inspectors and reliability of results. Samples
for the proficiency testing were prepared by pulverizing a standard reference
tablet of the appropriate drug and making serial dilutions with starch to obtain
concentrations of 0, 40, and 100%. The samples, which were labeled only with the
drug name and an identifying letter, were given to inspectors for quality
screening using Minilab procedures. In round 1 of the proficiency test, only 3 of
28 substandard samples were correctly identified. Round 2 of the proficiency
test, which was administered after a performance qualification test for the
analytical method, showed much improvement: 19 of 27 substandard drugs were
correctly identified, while 5 out of 9 inspectors made the correct inference on
the quality of 45 samples. However, in both rounds, 2 inspectors failed to
identify substandard samples, indicating that their technical competencies need
to be improved for the reliability of the results. Although the thin-layer
chromatography screening methods provide a rapid means for drug quality
assessment, they need to be put in the hands of competent users. The inclusion of
a proficiency test in the screening program provides a measure of determining
competency of the personnel and reliability of the results.
PMID- 17042180
TI - Determination of lomefloxacin in tablet preparations by liquid chromatography.
AB - A sensitive, precise, and specific high-performance liquid chromatography (HPLC)
method was developed for the assay of lomefloxacin (LFLX) in raw material and
tablet preparations. The method validation parameters yielded good results and
included the range, linearity, precision, accuracy, specificity, and recovery. It
was also found that the excipients in the commercial tablet preparation did not
interfere with the assay. The HPLC separation was performed on a reversed-phase
Phenomenex C18 column (150 x 4.6 mm id, 5 microm particle size) with a mobile
phase composed of 1% acetic acid-acetonitrile-methanol (70 + 15 + 15, v/v/v),
pumped isocratically at a flow rate of 1.0 mL/min. The effluent was monitored at
280 nm. The calibration graph for LFLX was linear from 2.0 to 7.0 mg/mL. The
interday and intraday precisions (relative standard deviation) were less than
1.0%. The method was applied for the quality control of commercial LFLX tablets
to quantitate the drug.
PMID- 17042181
TI - Evaluation of the International Organization for Standardization-International
Dairy Federation (ISO-IDF) draft standard method for detection of Enterobacter
sakazakii in powdered infant food formulas.
AB - As a result of the growing recognition of Enterobacter sakazakii as an emergent
pathogen, the International Dairy Federation (IDF) and the International
Organization for Standardization (ISO) have standardized a reference method for
the detection of E. sakazakii in milk powder products and powdered infant food
formulas (IFF). The objectives of this study were to assess the applicability of
the ISO-IDF draft standard, and to compare several chromogenic selective media
for E. sakazakii [ready-to-use ESIATM, homemade E. sakazakii isolation agar, and
Druggan-Forsythe-lversen (DFI) agar], and a selective media for
Enterobacteriaceae Violet Red Bile Glucose (VRBG). We found that the method is
sensitive, selective, and applicable to the analysis of powdered IFF, provided
that some modifications are added. In particular, definition of typical colonies
on chromogenic media should be less restrictive, and the possibility of using
chromogenic media other than ESIA should be introduced. Any of the chromogenic
media tested here could be used initially, since their performances were similar.
In these media, alpha-glucosidase-positive but non-yellow-pigmented isolates
should be also considered. Consequently, the yellow pigmentation test should be
abandoned, or completed with another test in order to select colonies to confirm.
Although the specificity of VRBG was relatively poor, it could be used as a
second nonchromogenic medium.
PMID- 17042182
TI - Two rapid methods for detection of Escherichia coli exceeding 10(4)/g action
levels: precollaborative study.
AB - The current AOAC Method 966.24 for enumeration of Escherichia coli in foods uses
a most probable number (MPN) procedure with extensive confirmation steps. Two new
methods based on membrane filtration (MF) were compared to the MPN reference
method for detection of high levels of E. coli in 5 food types, some of which
represent categories for which the U.S. Food and Drug Administration (FDA)
mandates additional testing if an action level of 10(4)/g E. coli is exceeded.
Ground beef, which is not FDA regulated, was also tested. The 5 food types were
all inoculated at 3 levels: 10(2)/g, > or = 10(4)/g, and > or = 10(5)/g E. coli.
An MF protocol using either m-ColiBlue24 (CB) or lauryl sulfate tryptose plus
BCIG (LST/BCIG) was an effective potential alternative to the reference method.
Sensitivity and specificity for both CB and LST/BCIG were 98 and 100%,
respectively. Agreement between MPN and both CB and LST/BCIG was 98%. The 2
proposed methods allow completion of both presumptive and confirmatory steps in 1
3 days, whereas the reference method requires as many as 11 days. Exclusivity
testing with 50 non-E. coli strains indicated 100% were correctly ruled out by
the proposed protocols. Inclusivity testing was used to determine whether typical
results were obtained after incubation of E. coli cultures on CB or LST/BCIG for
24 h. Of 50 E. coli strains tested, 100% yielded typical results after incubation
on CB, and 98% yielded typical results after incubation on LST/BCIG.
PMID- 17042184
TI - Collaborative trial for validation of a real-time reverse transcriptase
polymerase chain reaction assay for detection of central nervous system tissues
as bovine spongiform encephalopathy risk material: part 1.
AB - A collaborative trial was conducted to evaluate a real-time reverse transcriptase
polymerase chain reaction (RT-PCR) assay for detection of central nervous system
(CNS) tissues in meat products (e.g., sausages). The method is based on the
detection of ruminant glial fibrillary acidic protein (GFAP) mRNA by applying
real-time RT-PCR. The assay was evaluated through a multicenter trial involving
12 participating laboratories that received coded cDNA obtained from 3 different
types of sausages. The participants used 5 different real-time detection systems.
The results obtained in this validation revealed that this real-time RT-PCR assay
performed well in the different laboratories with a detection limit of at least
0.1% CNS in those test materials that contained strongly heat-treated samples
(sausages cooked at 120 degrees C) and the medium heat-treated samples (sausages
cooked at 80 degrees C). The detection limit of liver sausages was determined to
be 0.2% of CNS. Neither the samples with no CNS additive nor the bovine DNA and
the negative control containing 100% swine brain gave any positive signals. The
presented results indicate that the real-time RT-PCR assay was just as
reproducible between laboratories, as repeatable within a laboratory, could
reliably be used for detection of bovine spongiform encephalopathy risk material
in meat and meat products, and signify that it may be used with confidence in any
laboratory.
PMID- 17042183
TI - Interlaboratory study of the Charm ROSA Safe Level Aflatoxin M1 Quantitative
lateral flow test for raw bovine milk.
AB - An interlaboratory study of 21 public health, state agriculture, and industry
laboratories in the United States tested raw commingled bovine milk containing
aflatoxin M1 using the Charm Rapid One Step Assay (ROSA) Safe Level Aflatoxin M1
Quantitative lateral flow method. Blind coded sample pairs were fortified with 0,
300, 350, 400, 450, 500, and 550 parts per trillion (ppt) aflatoxin M1. A ROSA
reader quantitatively interpreted test strips with ppt readings. Readings < or =
400 ppt were interpreted as negative, and readings >400 ppt were interpreted as
positive. Initial positive samples were subsequently assayed 2 additional times.
If both retest results were >400 ppt, the sample was called positive/ actionable
relative to U.S. and Codex levels, 500 ppt. The concentration of 400 ppt was
chosen for the positive/negative interpretation to provide 90% sensitivity with
95% confidence at the 500 ppt legislative level. The combined false negative rate
was <5% (4 of 83) for samples at 500 and 550 ppt. The false violatives at 0, 300,
350, 400, and 450 ppt (n = 42 at each level) were 0, 0, 21, 14, and 93%,
respectively. The 90% positive concentration with 95% confidence was 503 ppt by
probit analysis. The average intralaboratory repeatability was 11% and average
interlaboratory reproducibility was 13% for the fortified sample pairs. High
performance liquid chromatography analysis of the study samples by 5 laboratories
showed 38% false negatives with the 500 and 550 ppt samples, and a 0% false
violative rate with samples less than the 500 ppt action level.
PMID- 17042185
TI - Determination of the acid value of instant noodles: interlaboratory study.
AB - An interlaboratory study was performed to evaluate the method for determining the
acid value of instant noodles, based on the Japanese Agricultural Standard (JAS),
with extraction of lipid using petroleum ether at a volume of 100 mL to the test
portion of 25 g. Thirteen laboratories participated and analyzed 5 test samples
as blind duplicates. Statistical treatment revealed that the repeatability (RSDr)
of acid value was <6.5%, and the reproducibility (RSDR) of acid value was <9.6%.
The HorRat values (RSDR/predicted RSDR) were 1.2-1.8, where the RSDR and the
predicted RSDR were obtained in terms of free fatty acids in the noodles per unit
weight, using the equation [acid value = percent free fatty acids (as oleic) x
1.99] and the extracted lipid contents. This method was shown to have acceptable
precision by the present study.
PMID- 17042186
TI - Interlaboratory transfer of a real-time polymerase chain reaction assay for
quantitative detection of genetically modified maize event TC-1507.
AB - A real-time polymerase chain reaction (QPCR) assay was developed for quantitative
detection of a genetically modified (GM) maize event TC-1507 and modification to
conventional PCR for qualitative purposes. Sequences 5'-flanking TC-1507 full
length insert were characterized and showed multiple rearrangements involving
insert and maize chloroplast fragments. The event specificity of the TC-1507
assays was based on the detection of transgene and plant rearranged sequences
found to 5' flank the insertion site. They were fully specific and exhibited a
limit of detection below 10 target copies, allowing consistent detection of 0.1%
GM levels. The QPCR was highly linear and efficient and proved adequate for
quantification of GM contents, aiming at the fulfillment of legal requirements
established in the European Union (i.e., compulsory labeling of TC-1507 levels
>0.9%). It satisfactorily determined TC-1507 contents on different matrixes and
was successfully transferred a different laboratory.
PMID- 17042187
TI - Determination of protein in milk powder using 2-sulfophenylazo-rhodanine as a
probe by the enhanced resonance Rayleigh light-scattering technique.
AB - In this paper, the interaction between 2-sulfophenylazo-rhodanine and protein was
investigated by Rayleigh light-scattering technique. Based on this, a novel
method for the determination of protein was developed. The effects of different
conditions, such as acidity and media, were investigated thoroughly, and the
optimum conditions were confirmed. Bis(2-ethylhexyl)sulfosuccinate (AOT)
microemulsion, which is introduced into the protein determination, markedly
increased the sensitivity of the system by changing the microenvironment. In pH
2.80 Britton-Robinson buffer solution in the presence of AOT microemulsion, the
detection limits of bovine serum albumin, human serum albumin, ovalbumin, and
gamma-globulin are 5.4, 4.5, 9.8, and 10.1 ng/mL, respectively. The method
developed in this paper has been applied to the determination of protein in milk
powder with satisfactory results.
PMID- 17042188
TI - Quantitation of Indian krait (Bungarus caeruleus) venom in human specimens of
forensic origin by indirect competitive inhibition enzyme-linked immunosorbent
assay.
AB - An indirect competitive inhibition enzyme-linked immunosorbent assay was reported
to detect krait venom in human specimens of forensic origin. Polyclonal anti
krait venom antibodies were characterized by indirect antibody capture assay. The
calibration plot was constructed based on linear regression analysis (y = 72.85 -
12.29x, r(2) = 0.98) with concentration ranges from 0.013 to 1000 ng/well of
krait venom with a limit of detection of 0.2 ng/mL in the assay system. The IC50
(inhibitory concentration at 50% displacement) value of krait venom was observed
to be 70 ng. Spiking studies indicated recoveries of 95-100% and 94-100% when
various concentrations of krait venom were spiked to rat tissues (skin, liver,
and kidneys) and pooled human serum, respectively. Polyclonal anti-krait venom
antibodies showed no cross-reactivity with cobra and viper venom when tested in
the assay system. The coefficient of variation of various concentrations of
working range in intra-assay (n = 6) was <5%, whereas in interassay (n = 6) it
was observed to be < or 7%. Further, the method was used to quantitate krait
venom in human autopsy and biopsy specimens of forensic origin. Concentration of
krait venom was found to be in the range of 4-172 ng/100 mg skin or skin
scrapings and 64-378 ng/mL blood or serum. The methodology may find application
in forensic laboratories to assess the cause of death in the cases of krait-bite
victims.
PMID- 17042189
TI - Development and in-house validation of a microbiological assay for determination
of cefepime in injectable preparations.
AB - Cefepime is a new parenteral cephalosporin that has been described as a fourth
generation, broad-spectrum antibiotic. This paper reports the development and in
house validation of an agar diffusion bioassay using a cylinder-plate method for
the determination of cefepime in powder for injection. The validation performed
yielded good results in terms of linearity, precision, accuracy, and robustness.
The assay is based on the inhibitory effect of cefepime upon the strain of
Micrococcus luteus ATCC 10240 used as the test microorganism. The results of
assays were treated statistically by analysis of variance (ANOVA) and were found
to be linear (r = 0.99993) in the selected range of 8.0-32.0 microg/mL; precise
[repeatability: relative standard deviation (RSD) = 1.39%, intermediate
precision: between-day RSD = 1.77%, and between-analyst RSD = 1.97%] and
accurate. Comparison of bioassay and liquid chromatography by ANOVA showed no
significant difference between methodologies. The results demonstrated the
validity of the proposed bioassay, which is a simple and useful alternative
methodology for cefepime determination in routine quality control.
PMID- 17042190
TI - Modification to the AOAC Sporicidal Activity of Disinfectants Test (Method
966.04): collaborative study.
AB - In an effort to improve AOAC Method 966.04, the Sporicidal Activity of
Disinfectants Test, selected modifications to the procedure were evaluated in a
collaborative study. Method 966.04 is used to generate efficacy data to support
the product registration of sporicides and sterilants. The method is a carrier
based test that provides a qualitative measure of product efficacy against spores
of Bacillus subtilis and Clostridium sporogenes. The use of garden soil extract
and the lack of standard procedures for the enumeration of spores and
neutralization of the test chemicals have been considered problematic for many
years. The proposed modifications were limited to the B. subtilis and hard
surface carrier (porcelain penicylinder) components of the method. The study
included the evaluation of a replacement for soil extract nutrient broth and an
establishment of a minimum spore titer per carrier, both considered crucial for
the improvement and utilization of the method. Additionally, an alternative hard
surface material and a neutralization confirmation procedure were evaluated. To
determine the equivalence of the proposed alternatives to the standard method, 3
medium/carrier combinations, (1) soil extract nutrient broth/porcelain carrier
(current method), (2) nutrient agar amended with 5 microg/mL manganese
sulfate/porcelain carrier, and (3) nutrient agar amended with 5 microg/mL
manganese sulfate/stainless steel carrier were analyzed for carrier counts, HCI
resistance, efficacy, quantitative efficacy, and spore wash-off. The test
chemicals used in the study represent 3 chemical classes and are commercially
available antimicrobial liquid products: sodium hypochlorite (bleach),
glutaraldehyde, and a combination of peracetic acid and hydrogen peroxide. Four
laboratories participated in the study. The results of the spore titer per
carrier, HCI resistance, efficacy, and wash-off studies demonstrate that amended
nutrient agar in conjunction with the porcelain is comparable to the current
method, soil extract nutrient broth/porcelain. The nutrient agar method is
simple, inexpensive, reproducible, and provides an ample supply of high quality
spores. Due to the current use of porcelain carriers for testing C. sporogenes,
it is advisable to retain the use of porcelain carriers until stainless steel can
be evaluated as a replacement carrier material for Clostridium. The evaluation of
stainless steel for Clostridium has been initiated by the Study Director. Study
Director recommendations for First Action revisions are provided in a modified
method.
PMID- 17042192
TI - Determination of benzimidazole fungicides in soil samples using microwave
assisted micellar extraction and liquid chromatography with fluorescence
detection.
AB - A simple and fast analytical method was developed for the determination of
benzimidazole fungicides (benomyl, carbendazim, thiabendazole, and fuberidazole)
in soil samples. The analytes were extracted from the soil samples by means of
conventional microwave-assisted extraction, using the non-ionic surfactants
polyoxyethylene 10 lauryl ether (POLE) and oligoethylene glycol monooalkyl ether
(Genapol X-080) as extractants. Determinations were made by using liquid
chromatography with direct fluorescence detection. The use of an analytical
column Symmetry C-18 offered short retention times of analytes without the need
of any pH regulators with mobile phase methanol-water (50 + 50, v/v). The best
results were obtained using 5% (v/v) POLE as extractant with recoveries of the
fungicides in spiked soil samples between 71 and 105%. The results were compared
with those obtained when Soxhlet extraction was applied to the same soil samples.
PMID- 17042191
TI - Microbiological assay for the determination of telithromycin in tablets.
AB - This study describes the development and validation of a microbiological assay,
applying the cylinder-plate method, for the determination of the antibiotic
telithromycin. The microbiological method consisted of a cylinder-plate agar
diffusion assay using Micrococcus luteus ATCC 9341 as the test microorganism. The
response graphs for standard and sample solutions were linear (r = 0.9987), and
no parallelism deviations were detected in the tested concentrations (0.25, 0.5,
and 1.0 microg/mL). The interday precision was 2.67%. Recovery values were
between 96.75 and 100.91%. A preliminary stability study of telithromycin showed
that the microbiological assay is specific for the determination of telithromycin
in the presence of its degradation products. The proposed method allows the
quantitation of telithromycin in pharmaceutical dosage form and can be used for
drug analysis in routine quality control.
PMID- 17042193
TI - Effect of ultrasound agitation on the release of heavy elements in Certified
Reference Material of human hair (CRM BCR 397).
AB - An ultrasonic-assisted leaching procedure was developed for the determination of
heavy elements (As, Cu, Cd, Pb, and Zn) in Certified Reference Material of human
hair (CRM 397) provided from the Community Bureau of Reference (BCR) of the
Commission of the European Community. Concentrated nitric acid-30% hydrogen
peroxide (2 + 1) was used for the leaching method. The effects of different
factors on acid leaching of elements, such as presonication time (without
ultrasonic stirring), sonication or exposure time to ultrasound, and temperature
of the ultrasonic bath have been investigated. Optimum values of these parameters
were selected for the maximum extraction of heavy metals from CRM BCR 397 and
human scalp hair samples of normal healthy males. To check the validity of the
proposed method, a wet acid digestion method was used to obtain the total
elemental concentration in CRM BCR 397 and scalp hair samples. Cu and Zn in
leachate and digests were measured by flame atomic absorption spectrometry using
a conventional air/acetylene flame, while As, Cd, and Pd were determined by
electrothermal atomic absorption spectrometry. Under optimized conditions, the
recovery for Zn, Cd, Pd, As, and Cu was 98, 98.5, 97.5, 98.2, and 95%,
respectively, of those obtained with the wet acid digestion method.
PMID- 17042194
TI - Single-laboratory validation of a method for the determination of furan in foods
by using static headspace sampling and gas chromatography/mass spectrometry.
AB - A headspace gas chromatography/mass spectrometry method was developed and
validated in-house for the determination of furan in foods. The method of
standard additions with d4-furan as the internal standard was used to quantitate
furan. The limit of detection and limit of quantitation (LOQ) values ranged from
0.2 and 0.6 nglg, respectively, in apple juice to 0.9 and 2.9 ng/g, respectively,
in peanut butter. Recoveries were obtained at 0.5, 1, 2, and 3 times the LOQ. At
1, 2, and 3 times the LOQ, the recoveries ranged from 89.4 to 108%, and the
relative standard deviations ranged from 3.3 to 17.3% for all the matrixes. For
apple juice, chicken broth, and infant formula, the averaged coefficients of
determination from the linear regression analyses were >0.99 with each food
fortified at 0.5, 1, 2, and 3 times the LOQ. The coefficients of determination
were >0.99 for green beans and 0.96 for peanut butter with the foods fortified at
1, 2, and 3 times the LOQ. Within-laboratory precision was determined by
comparing the amounts of furan found in 18 samples by 2 analysts on different
days with different instruments. For most of the foods, the difference between
the amounts found by each analyst was <18%. The method was used to conduct a
survey of >300 foods. The furan levels found ranged from none detected to 174
ng/g.
PMID- 17042195
TI - Determination of eight synthetic pyrethroids in bovine fat by gas chromatography
with electron capture detection.
AB - Synthetic pyrethroids are among the most widely used classes of insecticides, and
their uses are varied, including plant protection, animal dips, and as a
treatment for human clothing and bedding in very hot climates. Veterinary
applications include ear tags, pour-on formulations, sprays, and dips. Persistent
residues have been reported in livestock, and routine monitoring programs in
other countries have found detectable residues of various pyrethroids in fat. A
method has been developed using solid-phase extraction that reduces the
quantities of solvents used, the time required, and the amount of glassware used
compared to an earlier method on which it was based. The scope of analytes tested
included the 5 compounds cited in the earlier method (flucythrinate, permethrin,
cypermethrin, fenvalerate, and deltamethrin) and, in addition, cyfluthrin, lambda
cyhalothrin, and fluvalinate. Sample extracts were analyzed by gas chromatography
with electron capture detection using selected chromatographic peaks
characteristic of each compound. Limits of quantification for the compounds were
from 25-50 microg/kg, with a linear response for all compounds to 200 microg/kg.
Recoveries ranged from 80 to 123%.
PMID- 17042196
TI - Determination of chloramphenicol in royal jelly by liquid chromatography/tandem
mass spectrometry.
AB - A liquid chromatographic/tandem mass spectrometric method was developed and
validated for the determination of chloramphenicol (CAP) in royal jelly. Royal
jelly samples were first denatured with lead acetate solution, and the CAP was
extracted with solid-phase extraction before separation by liquid chromatography.
A triple-quadrupole mass spectrometer operated in the negative electrospray
ionization and selected-reaction monitoring mode was used for the detection of
CAP. For method validation, royal jelly samples were fortified at CAP levels
between 0.1 and 10.0 microg/kg; at these levels, recovery values (internal
standard-corrected) ranged from 93.3 to 105.0%, and the within-laboratory
reproducibility (relative standard deviation) was < or = 9.1%. The decision limit
was 0.07 microg/kg, and the detection capability was 0.1 microg/kg.
PMID- 17042197
TI - Simultaneous determination of florfenicol and florfenicol amine in fish, shrimp,
and swine muscle by gas chromatography with a microcell electron capture
detector.
AB - A rapid and sensitive gas chromatography method was developed for the
simultaneous determination of florfenicol (FF) and its metabolite florfenicol
amine (FFA) in fish, shrimp, and swine muscle. The extracted samples were
defatted with hexane and cleaned up by solid-phase extraction using Oasis MCX
cartridges. The eluate was evaporated to dryness, and residues were derivatized
and determined by gas chromatography with a microcell electron capture detector.
Overall average recoveries ranged from 81.7 to 109.7% for fish, 94.1 to 103.4%
for shrimp, and 71.5 to 91.4% for swine muscle. The detection limit was 0.5 ng/g
for FF and 1 ng/g for FFA, respectively. The method was validated for the
determination of incurred swine muscle samples in an actual residue study.
PMID- 17042198
TI - Patient's page. Oral health care for older patients.
PMID- 17042199
TI - The dental profession's relationship with third party carriers. 1976.
PMID- 17042200
TI - Muskogee's first dentist was talented singer as well.
PMID- 17042201
TI - Five questions dentists should ask about their money.
PMID- 17042202
TI - The Health Professional Program (HPP).
PMID- 17042204
TI - [Non surgical management of ectopic pregnancy].
AB - During the past 25 years, the incidence of ectopic pregnancy has progressively
increased while the morbidity and mortality have substantialy decreased, and the
treatment has progressed from salpingectomy by laparotomy to conservative surgery
by laparoscopy and more recently to medical therapy with Methotrexate or
expectant management. This therapeutic transition from surgical emergency to non
surgical managment has been attributed to early diagnosis through the use of
sensitive assays for hCG and the high definition of vaginal ultrasound. By using
these sensitive diagnostic tools, we are now able to select those patients who
are most likely to respond to expectant or medical managment versus those who are
at high risk of rupture and require surgery. We have reviewed the scientific
literature on ectopic pregnancy published over the past 20 years, with the aim to
assess the value of non surgical managment of etopic pregnancy. Predictor factors
of expectant managment are discussed. Medical therapy with methotrexate: results,
indications, Unpleasant side effects and complications are detailed. Several
protocols are defined and therapeutic supervision is etablished. The authors
offred several recommandations for OB/GY wich will optimize the effectivness of
non invasive methods for treatment of ectopic pregnancy.
PMID- 17042205
TI - [Prospective study of 420 biopsies realised in patients with duodenal ulcer with
positive Helicobacter pylori].
AB - It's a prospective study leaded between September 1997 and july 1999 (23 months )
in 75 patients with duodenal ulcer and positif for Helicobacter pylori. All
patients had a first endoscopy with antral, fundic and duodenal biopsies,
followed one month later by a second control fibroscopy with biopsies of the same
sites. A total of 420 biopsies was realised. Chronic gastritis was evaluated
according to sydney system. Patients was divided by randomisation in 4 groups.
Every group was received a different therapeutic association. The results was
conform to liberation concering activity 80%, intestinal metaplasia 12%.
inflammation 100%. Atrophy was observed in 56% of cases, this percentage is
variable in literature; chronic gastritis was predominant in antre relatively to
fundus (p<0.005). After treatment, a significative fall of Helicobacter pylori
and activity and atrophy was established, contrarity to intestinal metaplasia and
chronic inflammation witch are persisted. The prevalence of follicular gastritis
was 57%. The better rate of ulcer cicatrisation and Helicobacter pylori
eradication was respectively of 79% and 66% in group 1 treated by omeprazol,
amoxcillin, metronidazol by comparison with the others 3 groups (p<0.005).
PMID- 17042206
TI - [Return to work after acute myocardial infarction].
AB - OBJECTIVES: The aim of this work was to study the professional repercussions of
acute myocardial infarction and to analysis medical, social and occupational
factors which could influence return to work. MATERIAL AND METHODS: Our study
concerns 70 patients less than 66 years old, working before their hospitalization
and having been admitted for acute myocardial infarction between January 1-st,
1999 and December 31, 2000 in the Department of Cardiac Resuscitation of hospital
La Rabta of Tunis. Data were collected from retrospective review of folders and
answers to a questionnaire for which the patients have been summoned in 2002.
RESULTS: There were 70 patients almost exclusively men (n=69). The mean age was
49.0 +/- 6.8 years. The mean follow-up was 27.2 +/- 7.7 months. Sixty one
patients (87.1%) have initially been back to work and eight of them lost it
secondarily. The average delay of return to work has been 91+/- 111 days. The
direct repercussions of myocardial infarction on the professional capacities was
observed at the majority of patients. CONCLUSION: Despite an important
professional repercussions of acute myocardial infarction, our study showed a
high rate of return to work with relatively short delays.
PMID- 17042207
TI - [Ovary teratoma. Report of 91 cases].
AB - OBJECTIVE: To analyse the clinical and anatomic aspects of cystic teratomas of
the ovary, caracteristics of patients having cystic teratomas and the management
trends at our institution. STUDY DESIGN: Retrospective study of 91 cases of
cystic teratomas of the ovary diagnosed and treated at Farhat -Hached Hospital
(Sousse) between 1 january 1995 and 30 june 2003. RESULTS: Cystic teratomas
constituted 12.13% of all ovarian tumors diagnosed and treated at our institution
during the study period. The median of age was 33.35 ans. Abdominal or pelvic
pain was the most frequent symptom for presentation in 67% of the cases. In
addition; incidental finding was noted in 25.3% of the cases and swelling in 23%
of the cases. The mean tumor diameter was 10 cm. The rate of bilateral cystic
teratomas of the ovary was 14.3%. 19.8% of cystic teratomas has occurred in
pregnancy. The operative video-laparoscopy was employed in 9 cases, laparotomy
was employed in82 cases. Histopathological evaluation has detected 96.7% cases of
mature teratomas, and 3.3% cases of immature teratomas. CONCLUSION: Cystic
tertomas are the most common ovarian neoplasms, that occurs most commonly during
the reproductive years. The operative laparoscopy is the most common modality of
treatment of mature cystic teratomas. Immature teratomas must be treated by
laparotomy associated if necessary to chimiothrapiy.
PMID- 17042208
TI - [Lobular idiopathic granulomatos mastitis. About 10 cases].
AB - Our retrospective study was performed on 10 cases of granulomatous mastitis
registered in Obstetric Gynaecology Department and Pathology Department of CHU F.
Hached, Sousse, during 8 years period. The mean age was 36.4 years (range 32-59).
Among these 10 cases. 8 were observed in reproductive-age women and 2 were noted
in menopausal women. Clinical findings showed unilateral breast nodule associated
with inflammatory signs in 4 cases, mammelonary retraction in 2 cases and serous
or sero-purulent mamelonnary flow in 4 cases. Mamnmographic examination suggested
a malignant tumor in 5 patients. In all cases, the diagnosis is made by
histopathology. Surgical treatment consisted in wide excision with drainage or
radical mastectomy, eventually with combination with antibiotic therapy and non
steroid anti-inflammatory drugs. Prognostic features showed a good cicatrization
in 4 cases, local recurrence and cutaneous fistulization in one patient.
Granulomatous mastitis aetiology is still unclear, auto-immune aetio-pathogenesis
appears more interesting and should be clarified.
PMID- 17042209
TI - [Cor triatriatum: of six operated patients report].
AB - Six cases of cortriatriatum operated between January 1990 and April 2004. Their
ages ranged from 3 months to 22 years. Associated lesions are present in 4
patients. They consisted mostly of interatrial defects. The echocardiography has
been considered the procedure of choice for the diagnosis. Results of surgery
were excellent for all patients with a mean follow up of 5 years.
PMID- 17042210
TI - [Cardiac involvement in Emery-Dreifuss muscular dystrophy: a case report].
AB - Emery Dreifuss muscular dystrophy (EDMD) is an uncommon hereditary myopathy
characterized by 3 symptoms: slow progressive muscular atrophy, muscular
contractures and cardiac disease which affect prognosis. We report a 22 year-old
patient with EDMD which shows the typical features of the associated dilated
cardiomyopathy, ventricular arrhythmia, atrio-ventricular block, atrial
standstill then atrial paralysis.
PMID- 17042211
TI - [Retro-peritoneal liposarcoma. About 5 cases and revue of literature].
AB - Liposarcomas are malignant mesenchymatous tumors developed from elements
constituting the greasy tissue in various stages of differentiation. It is one of
the most frequent mesenchymatous sarcomas. Retro-peritoneum is a privileged site
of development in 12 to 15% of cases. During 9 years, from 1994 till 2002, we
have colligated and operated 5 cases of retro-peritoneal liposarcomas. Average
age was 50 years (extremes 34 to 79 years) with a sex-ratio of 1.5. Diagnosis was
late beyond 6 months. Abdominal pain and the appearance of an enormous mass (20
cm) were the revealing signs. No imagery method allowed to evoke the diagnosis.
The cyto-puncture realized once, was not able to determine with precision the
histological type. Immunohistochimy occupies nowadays an important place to
classify a sarcoma. Large surgical resection realized in 5 cases did not allowed
the complete ablation of the tumour in 3 cases considering the advanced loco
regional extension, which was at the origin of 3 recurrences. Well differentiated
histological type was noted in 3 cases, myxoid type in a case and not
differentiated type in a case.
PMID- 17042212
TI - [Idiopathic renal vein thrombosis. About two cases].
AB - Renal vein thrombosis is a rare pathology difficult to diagnose. It has quite
various clinical expressions and biological consequences. The diagnosis is based
upon radiologic explorations. This entity may have various causes. Detecting this
condition may lead to restoration of renal function compromised by renal vein
thrombosis. The treatment of renal vein thrombosis is mainly medical and based on
anticoagulants. The role of fibrinolytic treatment is controversial. Surgery is
exceptional. We report two cases of idiopathic thrombosis of the renal vein in
adult patient. Also, we have done a review of the literature on this clinical
syndrome and its diagnostic and therapeutic aspects.
PMID- 17042213
TI - [Intra vesical explosion during an endoscopic resection of a vesical tumor].
AB - The intra vesical combustion of hydrogen and oxygen, form one mixture of
explosive gas. Intra vesicale explosion during trans urethral resection is one
rare incident. Its most dangerous manifestation during is vesical rupture. We
demonstrate one case of intra vesical explosion during one endoscopic resection
of one in the anterior face tumor of bladder. Damages on bladder are small. By
going back to literature, we try to discuss the origin of intra vesical hydrogen
and oxygen as well as the different preventive measures.
PMID- 17042214
TI - [Scleredema of Buschke. A case report].
AB - Scleredema of Buschke is a rare disease whose aetiology remains unknown. It is
characterised by symetric skin induration of the upper part of the body which
usually resolve spontaneously. It can be associated with extra-cutaneous
symptoms. We report a new case in a 55 year old women.
PMID- 17042216
TI - [Common bile duct distomatosis managed by coelioscopic aproach. One case report].
AB - Biliary distomatosis is caused by a parasitis of trematode family: the fascialo
hepatica. It is a rare affection in Tunisia. The diagnostic is often done in the
status phase. Adult parasite stay preferentially at biliary ducts, cause
obstruction and cholangitis. The authors report a case of biliary treated
successfully by laparoscopic procedure.
PMID- 17042215
TI - [Thyrotoxicosis revelated by bilateral hip fracture].
AB - Hyperthyroidism is an important cause of secondary osteoporosis and therefore of
fractures. Nevertheless, facing an osteoporotic fracture, we do not
systematically seek after such thyroid disorder in our daily practice. In this
purpose, we report the case of 73 year old women, presented with a bilateral
pathological femoral neck fracture. Investigations find a hyperthyroid related
osteoporosis. Beyond orthopaedic treatment, radioiodine and bisphosphonate drugs
were prescribed.
PMID- 17042217
TI - [Tubo-ovarian actinomycosis. A report of two cases and literature review].
AB - Actinomycosis is an infection due to an anaerobic Gram-positive bacilus bacteria:
Actinomyces. Tubo-ovarian locallisation is rare. It more often appears clinically
as a pseudo-tumoral and feverish syndrom, evoking wrongly a malignant tumoral
pathology, and often leads to a mutilating surgical treatment. Intra-uterine
device appears as the principal favorable factor of this pathology. Basing on two
cases reported by the authors, and after literature review, physiopathology,
clinical and paraclinical expression, and treatment of this affection are
discussed. A set up is made.
PMID- 17042218
TI - [Eccrine poroma of the scalp: A study of three cases].
AB - The eccrine poroma is a rare benign sudoral tumour, which creates a fleshy
formation. The diagnosis is made according to the anatomopathological study. The
usual site is the sol, but in rare cases, other sites have also been reported.
The authors report three cases of eccrine poroma localised in the scalp with
literature review.
PMID- 17042219
TI - The two faces of capital femoral epiphyseal injury--new treatment paradigms
against the perceived myths.
PMID- 17042220
TI - Functional outcome after major lower extremity amputation: a survey on lower
extremity amputees.
AB - The post-operatve course of amputees is poorly documented. This cross-sectional
survey was unertaken to determine functional outcomes of 213 patients who had
undergone either a below-knee or above-knee amputation from 2000 to 2002 in a
state-hospital setting. The study comprises a self-constructed questionnaire and
interview conducted by phone. Of the 213 amputees, 41 out of 61 documented
telephone numbers of the patients were useful for contact. Only 30 amputees were
available for the study as the remaining 11 had passed away. Included in the
questionnaire was the modified Barthel Index, a measurement to assess the
amputees' ability to carry out activities of daily living (ADL). It contains ten
questions pertaining to ADL with a total score of 20 points. Two-thirds of the
respondents (67%) use their prosthesis for less than six hours per day. The
Barthel Index of 30 patients ranged from 9-20 (mean 17.7). However, the mean
Barthel Index in those with and without prosthesis was 18.4 and 15.2
respectively, but this difference was not significant. Half of the respondents
were unable to maintain their pre-amputation jobs, while the remaining 50% were
still able to work. Forty seven percent of amputees took less than a year to
return to their activities, while 33% took between one to two years. Regarding
the adequacy of preamputation information provided by the doctors, 73% amputees
responded in the affirmative, while 27% felt otherwise. Amputees were still
facing substantial disabilities following major amputation of the lower limb.
Although 80% of respondents surveyed own prosthesis, the full use of prosthesis
is suboptimal due to prosthetic-related problems. Most amputees had a good
functional outcome based on the modified Barthel Index. Some amputees were
unhappy as they felt that they were insufficiently informed regarding post
amputation expectation prior to the amputation. Despite good support from family,
the community support for amputees is still lacking.
PMID- 17042221
TI - Alteration of foot temperature in diabetic neuropathy: is it another piece of
puzzle?
AB - Poor glycaemic control and the duration of diabetes mellitus are known to
accelerate development and progression of neuropathy. Diabetic co-morbidities:
hypertension and hyperlipidaemia, have been postulated to associate with
development of neuropathy. A diabetic foot with low temperature and frequent
exposure to low temperature environment has recently been hypothesized to be at
higher risk to develop early neuropathy. This cross-sectional study is undertaken
to identify risk factors for diabetic neuropathy and the association between foot
temperature and development of diabetic neuropathy by using simple clinical
examination in the outpatient setting. From April 18, to April 30, 2005,
universal sampling method was used to select 134 diabetic patients (type 1 or
type 2 for >1 year) with peripheral neuropathy. Excluded are those with chronic
alcoholism, drug-induced neuropathy, dietary history of vitamin B deficiency and
family history of porphyria and hereditary sensorimotor neuropathy. The patient's
duration of diabetes, glycaemic control status and the presence of co-morbids:
hypertension and hyperlipidemia, were recorded. The temperature of the foot was
measured by using thermo buddy. Of 134 patients representing Malaysian ethnic
distribution with an equal number of males and females, 20.1% were in the age
group of 61 to 65 years and, 85.1% and 67.9% belonged to lower socioeconomic and
educational groups respectively. Associations between diabetic neuropathy and
glycaemic control (p = 0.018) and duration of diabetes (p < 0.05) were
significant. However, hypertension, hyperlipidaemia and low foot temperature were
not significantly associated with development of diabetic neuropathy. Poor
glycaemic control is significantly associated with diabetic neuropathy. Foot
temperature alteration is merely an effect of autonomic neuropathy with a cold
foot is attributed to co-existing peripheral arterial disease.
PMID- 17042222
TI - Bacteriology of diabetic foot lesions.
AB - Infection plays a pivotal role in enhancing a diabetic foot at risk toward
amputation. Effective antibiotic therapy against the offending pathogens is an
important component of treatment of diabetic foot infections. Recognition of the
pathogen is always difficult as the representative deep tissue sample for culture
is surrounded by ulcer surface harbouring colonies of organisms frequently
labelled as skin commensals. The emergent of resistant strains represents a
compounding problem standing against efforts to prevent amputation. This study
was undertaken to identify the pathogens associated with diabetic foot infection
in terms of their frequency and sensitivity against certain commonly used
antibiotics. Forty-four consecutive patients with open diabetic foot infections
had wound swab taken for culture and sensitivity testing. Cultures positive were
observed in 89% of the cases with Staphylococcus aureus, Klebsiella pneumoniae,
Pseudomonas aeroginosa encountered in 20%, 14% and 14% of cases respectively.
Mixed growths were isolated in 6% of cultures. All Staphylcoccus aureus isolates
were resistant to Penicillin but 80% were sensitive to Erythromycin and Co
trimoxazole. Klebsiella pneumoniae isolates were sensitive to Methicillin and
Gentamycin in 80% and 60% of cases respectively, and resistant to Ampicillin and
Ceftazidime in 83% and 50% respectively. All Pseudomonas aeroginosa isolates were
sensitive to Amikacin and Ciprofloxacin but 50% were resistant to Gentamycin.
There was no single antibiotic possessing good coverage for all common organisms
isolated from diabetic foot lesions. Staphylococcus aureus remains the
predominant cause of diabetic foot infections followed by Klebsiela pneumonia and
Pseudomonas aeroginosa. Most infections are monomicrobial. The emergence of
multiresistant organisms is a worrying feature in diabetic foot infections.
PMID- 17042223
TI - Necrotizing fasciitis of the lower limb: an outcome study of surgical treatment.
AB - Necrotizing fasciitis is a limb- and life-threatening rapidly spreading infection
affecting the deep fascia with secondary necrosis of the subcutaneous tissue. It
requires immediate medical attention and emergency surgery to prevent morbidity
and death. This study was undertaken to determine its co-morbidity and risk
factors affecting the outcome of its surgical treatment. This is a retrospective
review of 36 cases of necrotizing fasciitis of the lower limb treated in our
center between 1998 and 2002. Only 19% of the cases were correctly diagnosed upon
admission and 48.6% were initially diagnosed as 'cellulitis'. Diabetes mellitus
was the most common co-morbid. Pseudomonas, Staphylococcus, Streptococcus and
Enterobactericae were the common pathogens isolated. Ten patients (27.8%) had
major amputation as part of radical debridement. The overall mortality rate was
36% with laboratory parameters: high serum urea and creatinine, and low
haemoglobin levels were predictors for higher mortality. Poor white cell response
which is common in diabetic patients and a delay in surgical debridement were.
notable attributes to a higher mortality. Necrotizing fasciitis is a serious
infection associated with significant morbidity and mortality. A poor white blood
cell response, high serum urea and creatinine, and low haemoglobin level were the
predictors for mortality. Early diagnosis and prompt treatment are of paramount
importance in the treatment of this infection.
PMID- 17042224
TI - Antimicrobial properties of erythromycin and colistin impregnated bone cement. An
in vitro analysis.
AB - Deep surgical site infection is a devastating consequence of total joint
arthroplasty. The use of antibiotic impregnated bone cement is a well-accepted
adjunct for treatment of established infection and prevention of deep orthopaedic
infection. It allows local delivery of the antibiotic at the cement-bone
interface and sustained release of antibiotic provides adequate antibiotic
coverage after the wound closure. Preclinical testing, randomised and clinical
trials indicate that the use of antibiotic-impregnated bone cement is a
potentially effective strategy in reducing the risk of deep surgical site
infection following total joint arthroplasty. The purpose of this study was to
assess antibacterial activity of erythromycin and colistin impregnated bone
cement against strains of organisms' representative of orthopaedic infections
including Gram-positive and Gram-negative aerobic organisms: Staphylococcus
aureus, coagulase-negative Staphylococci, Enterococcus sp., Proteus sp.,
Klebsiella sp., Pseudomonas sp., and Escherichia coli. Pre-blended Simplex P bone
cement with the addition of erythromycin and colistin (Howemedica Inc) was mixed
thoroughly with 20ml liquid under sterile conditions to produce uniform
cylindrical discs with a diameter of 14mm and thickness of 2mm. 24-48 hour agar
cultures of Staphylococcus aureus, coagulase-negative Staphylococci, Enterococcus
sp.,Proteus sp., Klebsiella sp.,Pseudomonas sp., and Escherichia coli were used
for the agar diffusion tests. The agar plates were streaked for confluent growth
followed by application of erythromycin and colistin impregnated bone cement disc
to each agar plate. The plates were incubated at 30 degrees C and examined at 24,
48, 72 hours, and four and five days after the preparation of the impregnated
cement. The susceptibility of Staphylococcus aureus to the control discs was most
clearly demonstrated showing a distinct zone of inhibition. The zone observed
around coagulase-negative Staphylococci, Klebsiella sp., Pseudomonas sp., and
Escherichia coli were also significant. However, there was no zone of inhibition
or signs of antibacterial activity at the cemented surface were detected around
discs with Enterococcus sp. and Proteus sp. The results showed that Simplex P
bone cement with the addition of erythromycin and colistin was effective against
most of the broad spectrum organisms encountered during total joint arthroplasty.
The activity of Simplex P bone cement impregnated with erythromycin and colistin
is mainly during the first 72 hours.
PMID- 17042225
TI - Biomechanical properties of bone cement with addition of cefuroxime antibiotic.
AB - Antibiotic-loaded bone cement has been used as prophylaxis against infection in
total joint replacement surgery. Its effect on the mechanical strength of cement
is a major concern as high dose of antibiotic was associated with a significant
reduction in mechanical strength of bone cement. However, the cut-off antibiotic
that weakens the mechanical strength of cement remains to be determined. This
study was undertaken to observe the changes in the mechanical properties of bone
cement with gradual increments of Cefuroxime antibiotic. Cefuroxime at different
doses: 0, 1.5, 3.0 and 4.5gm were added to a packet of 40gm bone cement (Simplex
P) and study samples were prepared by using third generation cementing technique.
Mechanical impact, flexural and tensile strength were tested on each sample.
Significant impact and tensile strength reduction were observed after addition of
4.5 gm of Cefuroxime. However, flexural strength was significantly reduced at a
lower dose of 3.0 gm. The maximum dose of Cefuroxime to be safely added to 40mg
Surgical Simplex P is 1.5gm when third generation cementing technique is used.
Further study is needed to determine whether it is an effective dose as regards
to microbiological parameters.
PMID- 17042226
TI - Spinal injuries in a level-one trauma centre: a demographic study.
AB - The incidence of spinal injuries in Malaysia is on the rise following similar
trend of rapid development and increasing number of building constructions sites,
and motor vehicles. This epidemiological study was aimed at compiling local data
with a view to identifying target areas for preventive measures as well as
improvement strategies in the management of these potentially devastating
injuries. Seventy eight patients admitted with spine trauma in 1998 in a level
one trauma centre were retrospectively reviewed. All records were traced from the
admission and discharge books of the orthopaedic wards, accident and emergency
wards, operative registration book, spinal rehabilitation ward and orthopaedic
registration data of the Department of Orthopaedics, Hospital Kuala Lumpur.
Details on pre-treatment neurological and radiological level of injury and post
treatment outcomes were recorded according to the American Spinal Injury
Association (ASIA) impairment scale. Most patients (61.5%) were in the productive
ages of less than 34 years with a 4:1 male to female ratio. Majority were due to
motor vehicle accidents (57.7%) and fall from a height (28.3%). The thoraco
lumbar junction was the most common site of injury followed by the lower cervical
region with 62.5% of which associated with neurological deficit. Neurological
deficits: 11 ASIA-A, 1 ASIA-B, 6 ASIA-C, and 3 ASIA-D were detected in 21 (27%)
patients with fall from height (50%) particularly landing on the feet (50%) and
recreational sports (100%) were the risk factors. Less than 10% of patients were
treated surgically and this explains an average 39.4 days of hospitalization (5
times longer in patients treated non-operatively). On discharge, four patients
with incomplete neurology recovered to ASIA-E status and the remaining improved
to ASIA-C and -D in one and five patients respectively. Only one patient with
complete neurology improved to ASIA-B status following surgical treatment. The
demographic profiles of our patients were comparable to other series in the
literature but still inadequate to provide enough epidemiological data. A
multicenter study to provide a larger pool of patients is needed.
PMID- 17042227
TI - Sliding compression screw fixation for delayed union/non-union of femoral neck
fracture: is it a viable option.
AB - Femoral neck fracture non-unions often present with significant difficult
treatment decision as regards to surgical options and the risk of complication.
We present three cases of femoral neck non-union treated with double screw
stabilization technique using sliding compression hip screw and anti-rotational
screw. The rationale for opting to these simple implants in our setting is
discussed.
PMID- 17042228
TI - Screw osteosynthesis of displaced lateral humeral condyle fractures in children:
a mid-term review.
AB - Displaced humeral condyle fractures in children are traditionally fixed with
smooth Kirschner wire at the expense of a risk of secondary displacement
following removal of wire. Screw fixation of such fractures has recently been
advocated as it provides stable fixation. We have been using screw osteosynthesis
for treatment of displaced lateral humeral condyle fractures in children in our
institution since the turn of this century. This study provides a midterm review
of treatment of such injuries with special regards to growth disturbances after
screw osteosynthesis and to assess rate of union with a view to formulate
guidelines for screw removal. We review the outcomes of screw osteosynthesis for
displaced lateral condyle fracture of the humerus (19 Milch type-1 and 15 Milch
type-II) in 34 children treated in our institution from January 2000 to March
2004. The average age of the patients was 6.1 years. The average follow up was
24.5 months. Screw osteosynthesis led to union (average 6.9 weeks) in all
patients with excellent results in 28 patients. Growth disturbances in the form
of lateral condyle overgrowth (2 patients), valgus deformity secondary to lateral
condyle avascular necrosis (2 patients) and fishtail deformity ((3 patients) were
recognized. The implants should not be removed until fracture union is
established. Screw osteosynthesis of the lateral humeral condyle fracture
prevents secondary fracture redisplacement and lateral condyle overgrowth is
probably related to hyperemic response to metaphyseal fixation and early removal
of implant before radiological union.
PMID- 17042229
TI - Adequacy of pain relief in closed manipulative reduction of fracture and
dislocation.
AB - Adequate pain relief is a requisite for a successful closed manipulative
reduction (CMR) of fractures and dislocations. This prospective study was
undertaken to assess the mode and adequacy of pain relief given to patients
undergoing such procedures at Seremban Hospital from the 1st April to the 31st
May 2001. All patients with fractures and dislocations scheduled to undergo CMR
were included in this study. The type of sedative agents and analgesia
administered were recorded. Demographic data and the type of fracture or
dislocation of the selected patients were documented. A visual analogue scale
(VAS) for pain perception was given to both to the patients and the medical
personnel who performed the procedure. All data were collected manually before
entered into computerized database for analysis. Of 72 patients included in this
study, 47% were Malay, 26% Indian, 21% Chinese and 6% others. There was male
predominance and the patients' age ranged between 9 to 79 years (average 27.4
years). Upper limb injuries (79%) were mainly fractures of the radius and ulna
(29%) and isolated fracture radius (21%). For the lower limb injuries (21%),
combined tibia and fibula fractures constituted 10% of the total cases followed
by isolated tibia fractures (10%) and hip dislocation (1%). The most common pain
relieving agents given during the CMR were intravenous pethidine alone (43%)
followed by combination of intravenous pethidine and valium (36%), intramuscular
pethidine (17%) and intramuscular tramal (4%). The Visual Analogue Score (VAS)
for pain perception revealed that 61% of the patients had moderate pain while 21%
had severe pain during the course of the procedures. Suboptimal pain relief
administered during CMR should prompt positive actions to ensure that the patient
is not subjected to undue pain just for the sake of an acceptable fracture
reduction.
PMID- 17042230
TI - Radiation exposure to operating theatre personnel during fluoroscopic-assisted
orthopaedic surgery.
AB - Orthopaedic procedures especially dynamic hip screw (DHS) fixation, interlocking
nailing (ILN) of the tibia and femur require fluoroscopic assistance. Frequent
exposure to radiation is a major concern to members of the orthopaedic surgical
team. This study was undertaken to measure shallow (skin) dose to the operating
team personnel and deep (whole body) dose to the surgeon during such procedures
in view to provide guidelines to the operating team members regarding the number
of procedures allowable for them to perform or assist annually. Skin dose for the
operating personnel and whole body dose for the operating surgeon during 25
procedures; ten cases of DHS, seven and six cases of ILN of the tibia and femur
respectively, was measured using Thermoluminescent Dosimeter (TLD) chips. The
shallow radiation dose for theatre personnel ranged from 0.19 mSy to 0.61 per
case while the deep dose for the surgeon was 0.28, 0.55 and 0.81 mSy for seven
cases of tibial ILN, ten cases of DHS and six cases of femur ILN respectively.
The surgeon has the highest radiation exposure than other theatre personnel and
the whole body exposure for DHS was higher than that of for ILN. However, the
estimated cumulative dose was still far below the permissible annual dose limit.
PMID- 17042231
TI - Delay in treatment of primary malignant and aggressive musculoskeletal tumours.
AB - Patients with aggressive musculoskeletal tumours often arrive at specialised
treatment centres late. Such a delay could mean disfavour for potentially curable
or long-term disease-free outcome of limb preserving surgery. This study was
undertaken to identify the underlying problem-related delay with a view to
propose solution for solving it. We reviewed 30 patients to determine the periods
of delay between onset of the first symptom and the definitive treatment. The
delays were categorized as 'patient' delay, 'referral' delay and 'treatment'
delay. There was 'patient' delay in 57% of patients (n=17), ranging from 1 to 18
months; 'referral' delay in 67% of patients (n=20) ranging from 1 to 19 months
and 23% of patients (n=7) had treatment delay (average 23 days) at the treatment
centre. The causes of late arrival are not solely patient-related but are
multifactorial. Measures to minimize such delays include enhancing awareness only
with high index of suspicion among primary care practitioners, creating a special
lane specialized imaging studies and establishing a dedicated musculoskeletal
tumour unit.
PMID- 17042232
TI - Forequarter amputation of the upper extremity for musculoskeletal tumors:
posterior approach revisited.
AB - Forequarter amputation entails surgical removal of entire upper extremity,
scapula and clavicle. Several techniques of forequarter amputation have been
described. The anterior approach has been the preferred technique of exploration
of axillary vessels and brachial plexus. The posterior approach has been
condemned to be unreliable and dangerous for most large tumor of the scapula and
suprascapular area. We describe a surgical technique using posterior approach of
exploration of major vessels for forequarter amputation of upper extremity in
eight patients who presented with humeral-scapular tumor. There were six patients
with osteosarcoma: three with tumor recurrent and three chemotherapy recalcitrant
tumors with vessels involvement. One patient had massive fungating squamous cell
carcinoma and another had recurrent rhabdomyosarcoma. Four patients had fungating
ulcer and six patients had multiple pulmonary metastases at the time of surgery.
The mean estimated blood transfusion was 900 ml (range 0-1600 ml) and two
patients did not require transfusion. The duration of surgery ranged 2.5-6.0
hours (mean 3.8 hours). Two patients with known pulmonary metastases required
post-operative intensive care monitoring. The mean duration of survival was 5.8
months. The posterior approach of exploring major vessels for forequarter
amputation of upper extremity with musculoskeletal tumor is safe and reliable.
PMID- 17042233
TI - A simple practical protocol for care of metal-skin interface of external
fixation.
AB - Patients treated with external fixation for limb reconsturciton or fracture
stabilization equire regular and prolongedperiod of pin-tract care involving
frequent visits to clinic and dressing traditionally carried out by trained
nurses or medical assistants. A simple method of do-it-yourself dressing was
introduced in our institution and this study was undertaken to evaluate the
effectiveness of the protocol. Sixty patients (40 trauma-related problems and 20
congenital or developmental disorders) were enrolled into the study. Following
application of external fixation, the patients and/or their caretakers were
taught on how to do pin-site dressing using normal saline or drinking water as
cleansing solution on daily basis. Patients were discharged on the second or
third post-operative day and were followed-up every two weeks for an average 182
days (range 66 to 379 days) with special attention on identifying pin-tract
infection. A simple grading system for pin-tract infections was proposed. Of 40
patients with trauma-related problems. 65% were post-traumatic infections. There
were 788 metal-skin interfaces (239 half-pin fixations and 549 tensioned wire
fixations. A total 143 metal-skin interface infections (18.1%) involving half-pin
sites (41.3%) and tensioned wire sites (58.7%) was noted. Majority were grade I
infections (79.7%), 18.8% grade II and only 1.4% grade III. Most infections
(81%)were caused by Staphylococcus aureus. Grade I infections were successfully
treated with frequent dressing, grade II by adjunctive oral antibiotic but grade
III infections required removal of fixator. All eventually healed. Do yourself
non-sterile dressing of metal-skin interfaces is a cost-effective method of pin
site care with a low infection rate. The infections were sucessfully treated
using guidelines according to the proposed classification of pin-tract
infections.
PMID- 17042234
TI - Recalcitrant post-traumatic chronic osteomyelitis/infected non-union of the tibia
following open grade-ill fractures: treatment with vascularized osteocutaneous
fibular graft.
AB - Post-traumatic chronic osteomyelitis and infected non-unions of the tibia
following severe type-III open fracture are difficult to treat Refractoy cases
often necessitate amputation despite attempts to salvage the limb. We report our
experience in treating such difficult cases with an alternative surgical option
using free osteocutaneous fibular graft. Eight consecutive patients with post
traumatic chronic osteomyelitis/infected non-union were treated surgically with
free vascularized osteocutaneous fibular graft. Outcomes in term of graft-host
union and complication were evaluated. Four patients had anastomotic venous
thrombosis requiring anastomotic revision. Five patients developed surgical site
infections needing extended antibiotic therapy to achieve resolution at an
average of 15.2 weeks. Fibular graft fracture occurred in three patients but all
grafts survived and united after a mean time to union of 42.3 weeks (range 31 to
82 weeks). At the final follow-up, union of host-graft junction and control of
infection were achieved in all patients except one who required a secondary
amputation. Free vascularized osteo-cutaneous fibular graft is a viable limb
salvage option for refractory chronic osteomyelitis or infected non-union
following treatment of grade-III open tibial fractures.
PMID- 17042235
TI - Slipped capital femoral epiphysis (SCFE): a 12-year review.
AB - Slipped capital femoral epiphysis (SCFE) is a relatively uncommon hip disorder in
adolescents and its prevalence in Malaysia has not been studied. This
retrospective study is undertaken to provide an overview of a 12-year review of
SCFE treated in our institution. Fourteen patients (19 hips) with slipped capital
femoral epiphysis (SCFE) admitted to Hospital UKM from 1990 to 2002 were reviewed
with respect to demographic profile, functional outcome according to the Iowa Hip
Score, and complications. There were ten boys (average age, 12.5 years) and four
girls (average age, 12 years). Eight were Malays and six were Indians. The
average body mass index was 26.1 verweight). The left hips (11 hips) were
affected more than the right hips (eight hips). Five patients had bilateral
slips. Thirteen hips were considered stable while the other six hips were
unstable. The majority of cases were moderate slips (12 hips), four hips had
severe slips while three hips had mild slips. Several methods of treatment were
instituted. These include in situ cannulated screw fixation (11 hips), Knowles
pin fixation (three hips) and gentle closed manipulative reduction with
cannulated screw fixation (three hips). One patient with bilateral slips refused
surgical treatment. Based on the Iowa Hip Score, most patients (nine) had
satisfactory results (excellent or good), three had fair results while one
patient had a poor result. Avascular necrosis developed in five hips while
chondrolysis occurred in one hip. In situ cannulated screw fixation is the
treatment of choice. SCFE is an uncommon condition in Malaysia.
PMID- 17042236
TI - The pattern of femoral diaphyseal fractures in children admitted in Sarawak
General Hospital.
AB - Trend towards changing the face of management for pediatric femoral fractures
tends to advocate operative treatment. This study was undertaken to review our
current practice in the wake of recent progress in the management of pediatric
femoral fractures. Fifty patients with femoral diaphyseal fracture treated in
Sarawak General Hospital were reviewed retrospectively after an average follow-up
of 2.6 years. There were 36 boys and 14 girls, with a mean age of 6.2 years
(range five months to 14 years). Children under six years of age constituted the
majority of the patients. Half of the fractures were caused by road traffic
accident. Nine patients had associated injuries. The most common site of fracture
was at the middle third (N=31). The treatment regimens were delayed hip spica
(DHS) in 16, immediate hip spica (IHS) in 24, plate osteosynthesis (PO) in five,
titanium elastic nailing (TEN) in five, and external fixation (EF) in one. The
minimum hospital stay was two days, and the maximum 33 days (mean, 9.7 days).
Malunion was the commonest complication. Conservative treatment is the preferred
option for children under six years of age. It is cost-effective with minimal
complication. The other treatment options are reserved for specific indication in
older children. Diaphyseal fractures of the femur in children can be adequately
managed non-operatively.
PMID- 17042237
TI - Apollo total knee replacements in University Malaya Medical Centre: a short-term
outcome.
AB - Total knee arthroplasty is the most preferred option for treatment of severe
osteoarthritis of the knee. We report the short-term outcome of 48 total knee
replacements in 31 patients utilizing the Apollo Total Knee System after an
average follow-up of 48 months (range 15 to 70 months). Records of all patients
who underwent TKA using Apollo Total Knee System were retrospectively reviewed.
Functional outcome was evaluated using visual analogue scale for pain rating and
the Oxford 12-item questionnaire. Postoperative radiographs of the replaced knees
were assessed by using the Knee Society Total Knee Arthroplasty Roentgenographic
Evaluation and Scoring System. Degenerative osteoarthritis was the commonest
indication for TKA. The average patient's age was 63.7 years (range, 30-77
years). The mean visual analogue scale for pre- and post-operative pain was eight
and zero respectively. The mean Oxford 12-item questionnaire score pre- and post
operatively was 44.8 and 16.5 respectively. Patient satisfaction was notable in
98% of the cases with an average improvement in arc of flexion of 111 degrees.
There were four failures; deep infection (one) and aseptic loosening (three)
giving rise to a 94% implant survivor. The short-term results of this series is
comparable with or better than a number of outcome studies of the Apollo Knee
System or other implants of similar design.
PMID- 17042238
TI - Venous gas embolism following hydrogen peroxide irrigation during debridement of
chronic osteomyelitis lesion.
AB - We report a case of a previously healthy 53-year-old man who developed an intra
operative catastrophic event occurring in association with the use of hydrogen
peroxide for wound irrigation following surgical debridement of a chronic
osteomyelitis lesion of the humerus. It is our intention to highlight this
potentially fatal consequence of hydrogen peroxide irrigation as part of bone
debridement procedure. This case will serve as a reminder to orthopaedic surgeons
who frequently use hydrogen peroxide in their surgical practice.
PMID- 17042239
TI - Marjolin's ulcer--a near forgotten entity.
AB - We report a case of a 55-year-old man who presented with a 6-month history of a
fungating ulcer on the right hand at the site of a previously healed ulcer that
had been present for 40 years. Histopathological examination of four-quadrant
biopsy specimens showed a moderately differentiated squamous cell carcinoma
(SCC). A transradiocarpal amputation with stump closure using radial flap was
performed as it was not possible to achieve a functionally and cosmetically
acceptable hand after a wide excision with 2 cm tumour-free margin. It is our
intention to highlight this rare condition as reminder to consider this entity as
a differential diagnosis of chronic non-healing skin ulcer.
PMID- 17042241
TI - Bilateral femoral neuropathy associated with disseminated intravascular
coagulopathy: a case report.
AB - We report a case of 20-year-old man who presented with bilateral femoral nerve
palsy following resuscitation for traumatic massive blood loss and its
consequence. A high suspicious index for this complication may lead to its early
recognition. Its related pathoanatomy is discussed based on the described
evidences in the literature. Nonoperative treatment remains as a recommended
option for coagulopathy-related neuropathy.
PMID- 17042240
TI - Transphyseal fracture-separation of the femoral capital epiphysis: a true SCFE of
traumatic origin.
AB - Acute traumatic transphyseal fracture of the capital femoral epiphysis is a rare
but serious injury. The injury is typically inflicted by a severe trauma. Because
of the vulnerability and predisposed anatomy of the femoral epiphysis in relation
to its blood supply, the fracture has been designated to have poor prognosis with
inevitable osteonecrosis and eventual deformity of the hip. We report a case of
such fracture in a 13-year-old child in view to highlight some of the anticipated
problems in the management of such injury.
PMID- 17042242
TI - Revision total hip arthroplasty using impaction bone grafting technique.
AB - A variety of reconstructive options exist for revision of both femoral and
acetabular components in total hip replacement surgery. The use of impaction bone
grafting with morsellised allograft has shown promising results in revision total
hip arthroplasty. It works as a biologic reconstitution of bone stock defects and
provides a solid construct with stable fixation. We present a case of bilateral
revision total hip arthroplasty with poor bone stock where reconstructive surgery
was done by using impaction bone grafting, mesh and C-stem implants.
PMID- 17042243
TI - Delayed treatment of decompression sickness with short, no-air-break tables:
review of 140 cases.
AB - INTRODUCTION: Most cases of decompression sickness (DCS) in the U.S. are treated
with hyperbaric oxygen using U.S. Navy Treatment Tables 5 and 6, although
detailed analysis shows that those tables were based on limited data. We reviewed
the development of these protocols and offer an alternative treatment table more
suitable for monoplace chambers that has proven effective in the treatment of DCS
in patients presenting to our facility. METHODS: We reviewed the outcomes for 140
cases of DCS in civilian divers treated with the shorter tables at our facility
from January 1983 through December 2002. RESULTS: Onset of symptoms averaged 9.3
h after surfacing. At presentation, 44% of the patients demonstrated mental
aberration. The average delay from onset of symptoms to treatment was 93.5 h;
median delay was 48 h. Complete recovery in the total group of 140 patients was
87%. When 30 patients with low probability of DCS were excluded, the recovery
rate was 98%. All patients with cerebral symptoms recovered. Patients with the
highest severity scores showed a high rate of complete recovery (97.5%).
DISCUSSION: Short oxygen treatment tables as originally described by Hart are
effective in the treatment of DCS, even with long delays to definitive
recompression that often occur among civilian divers presenting to a major Divers
Alert Network referral center.
PMID- 17042244
TI - Venous filling and elastance in the calf positioned above and below heart level.
AB - INTRODUCTION: Limb venous compliance is a major factor in determining the extent
of blood pooling during orthostatic stress. We measured the filling of the calf
and of its major veins at different postures and quantified the venous
contribution to the total volume shift of the calf. The results were also used to
determine the venous elastance and to gain some information on the filling of the
small veins. METHODS: Twelve healthy volunteers participated in the study. The
calf volume was measured with strain gauge plethysmography and the veins were
imaged with ultrasound in the following positions: supine, sitting with both legs
horizontal, sitting with one leg suspended, and supine with one leg raised. Cross
sectional areas of the imaged veins were calculated from the measured diameters.
Hydrostatic change in the venous pressure was assumed when calculating the venous
elastance. RESULTS: The maximal increase in the calf area was up to 1 cm2. The
large veins accounted for approximately 30% of the total volume shift of the calf
except in cases where the subjects had one leg suspended. Then, the contribution
of the large veins was less than 20%. The estimated elastance of the large veins
was 80 +/- 14 mmHg, which may be regarded as substantial. CONCLUSIONS: The study
suggests that there is a distinct difference in the filling of the small and the
large leg veins. The small veins may be the principal contributors to the total
compliance of the calf when the venous pressure is above 30 mmHg.
PMID- 17042245
TI - Cardiovascular regulation response to hypoxia during stepwise decreases from 21%
to 15% inhaled oxygen.
AB - INTRODUCTION: The classical view states that hypoxia beyond an oxygen
concentration of about 17% induces tachycardia. However, few studies have
investigated the dose-dependent effects of acute normobaric hypoxia on autonomic
nervous regulation of the cardiovascular system. Therefore, we evaluated the
effects of stepwise hypoxia on cardiovascular neural regulation and postulated
that acute normobaric hypoxia causes vagal withdrawal and sympathetic activation
from 17% 02. METHODS: There were 18 healthy men who were exposed to acute
stepwise normobaric hypoxia (21%, 19%, 17%, 15% 02). Spectral analysis of the RR
interval and BP variability were used. RESULTS: BP was not altered. Heart rate
significantly increased at 15% (21%, 59 +/- 2; 15%, 62 +/- 2 bpm). The low
frequency power of systolic BP variability (an index of vasomotor sympathetic
nerve activity) significantly increased at 15% (21%, 6.1 +/- 1.3; 15%, 9.9 +/-
1.3 mmHg2). The low-frequency power of the RR interval variability significantly
increased from 17% (21%, 1036 +/- 233; 17%, 1892 +/- 409; 15%, 1966 +/- 362 ms2),
However, the high-frequency power of RR interval variability (an index of cardiac
parasympathetic nerve activity) did not change. Associated with these changes,
the ratio of low- to high-frequency power of RR interval variability as an index
of relative cardiac autonomic balance significantly shifted toward sympathetic
dominance (21%, 1.5 +/- 0.3; 15%, 2.2 +/- 0.3). All indices of cardiac baroreflex
function (transfer function and sequence gains) were unchanged. DISCUSSION: These
results suggest that acute exposure to normobaric mild hypoxia (O2 > or = 15%)
induces increases in sympathetic vasomotor activity and cardiac sympathetic
dominance resulting in an increased heart rate. However, 15% O2 hypoxia might not
induce changes in static BP, vagal activity, or spontaneous arterial-cardiac
baroreflex function.
PMID- 17042246
TI - The sweating foot: local differences in sweat secretion during exercise-induced
hyperthermia.
AB - INTRODUCTION: Little is known regarding local differences in foot sweat
secretion. Since such information is important to our understanding of sweat
gland control for thermoregulatory modeling and for the design of footwear we
explored this topic. METHODS: Local sweat rates were investigated across core
temperatures from 37-39 degrees C, achieved using endogenous (cycling) and
exogenous heat (water-perfusion garment: 46 degrees C). Six healthy adults (three
men, three women) performed one-legged, incremental cycling in a heated, climate
controlled chamber (36 degrees C, 60% relative humidity). Sweat rates were
measured at the forehead and stationary (left) foot (capsules 3.16 cm2): three
dorsal sites (base of toes, second metatarsal, and mid point), the lateral, and
the central plantar surfaces. RESULTS: Terminal core temperatures ranged between
38.3-39.1 oC, with peak heart rates of 155-187 bpm. Most foot sweat rates were <
50% of that observed at the forehead: dorsal 1 (38%); dorsal 2 (54%); dorsal 3
(37%); lateral (24%); and plantar surfaces (18%). When averaged across the trial,
local sweat rates were: 2.61 (forehead); 0.98 (dorsal 1); 1.39 (dorsal 2); 0.95
(dorsal 3); 0.62 (lateral); and 0.47 mg cm2 2 min-1 (plantar). CONCLUSION: Two
key observations emerged. First, sweat secretion from the experimental foot
averaged 30 ml x h(-1), peaking in the last 5 min at 50 ml x h(-1). Second,
approximately 70% of the measured sweat flow emanated from the upper skin
surfaces, with only 30% coming from the plantar surface.
PMID- 17042247
TI - CO2 detection in closed-circuit oxygen divers with and without a distracting
task.
AB - INTRODUCTION: Elevated arterial PCO2 (hypercapnia) increases the risk of CNS
oxygen toxicity when diving with enriched oxygen gas mixtures. A CO2 detection
and retention test is conducted as a matter of routine at the Israel Naval
Medical Institute for physiological training, and as a screening tool for divers
who may be prone to suffer from CNS oxygen toxicity. This test does not include
an "attention distracter", which would provide a better simulation of the true
situation during actual diving. The purpose of the present study was to examine
the hypothesis that the addition of cognitive tasks to the CO2 detection and
retention test might alter divers' detection ability. METHODS: We assessed
ventilatory and perceptual responses to variations in inspired CO2 (range 0-5.6
kPa, 0-42 mmHg) during moderate exercise, with and without the addition of
cognitive tasks, in 15 Israel Navy combat divers on active duty. The first stage
was the CO2 detection training session, followed by the CO2 detection test
session (TEST) and the CO2 detection test session while doing cognitive tasks
(COGN). The latter two sessions were performed by some of the subjects in reverse
order. RESULTS: We found that the mean (+/- SD) PICO2 at the detection threshold
was significantly lower in the COGN (1.7 +/- 0.8 kPa, 12.7 +/- 6.0 mmHg) than in
the TEST (2.4 +/- 0.6 kPa, 18.1 +/- 4.5 mmHg). The mean PETCO2 while inspiring
5.6 kPa (42 mmHg) CO2 was not significantly different in the two tests.
CONCLUSION: We suggest that the ability to detect CO2 during a dive is not
impaired, but rather improves when the diver's attention is focused on other
tasks.
PMID- 17042248
TI - Caffeinated tube food effect on pilot performance during a 9-hour, simulated
nighttime U-2 mission.
AB - INTRODUCTION: Interventions to maintain performance are necessary to meet
demanding mission requirements during sustained and surge aviation operations.
Tube foods are the only foods that can be consumed during a U-2 mission due to
the confining and encapsulating nature of required support equipment. Caffeine is
a safe and effective strategy to enhance cognitive performance and is an
ingredient in some tube foods. The objective of this study was to determine
whether moderate doses of caffeinated tube foods would enhance performance in a
simulated U-2 mission. METHODS: Volunteers were 12 healthy USAF male pilots. The
study used a double blind, placebo-controlled, two-factor, repeated-measures
(five iterations per night) design. Caffeinated (200 mg each) or placebo tube
food was consumed at 00:00 and 04:00. Dependent measures assessed included
standardized tests of cognitive performance, vigilance, and mood designed to
simulate the demands of a nighttime U-2 mission. RESULTS: Statistically
significant (p < 0.05) improvements in performance due to caffeine administration
compared with placebo were present in all five cognitive tasks either as main
effects, interactions, or absence of significant degradation in the caffeine
treatment condition compared with the placebo condition. A majority of sleep
deprivation-induced performance decrements were attenuated by 200 mg of caffeine
in tube food consumed every 4 h, and in some cases, performance was improved
beyond baseline levels. CONCLUSIONS: Caffeinated tube food maintained cognitive
performance representative of U-2 long-duration mission tasks at or near baseline
levels for a 9-h overnight period in qualified USAF pilots. Side effects were
minor and did not differ between placebo and caffeine conditions.
PMID- 17042249
TI - Head rotation during vertical impact predicted using initial head angle and
anthropometry.
AB - INTRODUCTION: Dynamic inertial loading to the head and neck complex, similar to
what is experienced during the rocket boost phase of pilot ejection, results in
diverse kinematic responses when observed in live human volunteers. The purpose
of this study was to develop a predictive model of head rotation during the
compressive phase of pilot ejection. METHODS: Post hoc analyses were conducted on
data from two previous experimental studies. This analysis included observing 138
tests involving 27 human volunteers (both men and women) where the various
kinematic responses were categorized into five modes based on the location of
primary rotation and the direction of head rotation. Several statistical methods
(logistic regression, linear regression, and Fisher's Exact test) were employed
to evaluate the influence of independent variables, body anthropometry, and
initial head angle on dependent variables head acceleration and direction of head
rotation. RESULTS: Statistical results of this data indicated that initial head
position and body anthropometry are significant factors with respect to head
response during the compressive phase of an ejection. Two statistical tools were
developed; one to assist in predicting the location of primary head rotation, and
the other to predict the direction of head rotation. DISCUSSION: By using the two
statistical tools together, a simplified method was developed for predicting the
modes of head response to vertical impact based on initial position and
anthropometry. The results of this study show the importance of initial position
prior to an ejection and may assist in identifying individuals at greater risk of
injury during an ejection.
PMID- 17042250
TI - Neck muscle activation and head postures in common high performance aerial combat
maneuvers.
AB - INTRODUCTION: Neck injuries are common in high performance combat pilots and have
been attributed to high gravitational forces and the non-neutral head postures
adopted during aerial combat maneuvers. There is still little known about the
pathomechanics of these injuries. METHODS: Six Royal Australian Air Force Hawk
pilots flew a sortie that included combinations of three +Gz levels (1, 3, and 5)
and four head postures (Neutral, Turn, Extension, and Check-6). Surface
electromyography from neck and shoulder muscles was recorded in flight. Three
dimensional measures of head postures adopted in flight were estimated postflight
with respect to end-range of the cervical spine using an electromagnetic tracking
device. RESULTS: Mean muscle activation increased significantly with both
increasing +Gz and non-neutral head postures. Check-6 at +5 Gz (mean activation
of all muscles = 51% MVIC) elicited significantly greater muscle activation in
most muscles when compared with Neutral, Extension, and Turn head postures. High
levels of muscle co-contraction were evident in high acceleration and non-neutral
head postures. Head kinematics showed Check-6 was closest to end-range in any
movement plane (86% ROM in rotation) and produced the greatest magnitude of
rotation in other planes. Turn and Extension showed a large magnitude of rotation
with reference to end-range in the primary plane of motion but displayed smaller
rotations in other planes. DISCUSSION: High levels of neck muscle activation and
co-contraction due to high +Gz and head postures close to end range were evident
in this study, suggesting the major influence of these factors on the
pathomechanics of neck injuries in high performance combat pilots.
PMID- 17042251
TI - Pilot error and its relationship with higher organizational levels: HFACS
analysis of 523 accidents.
AB - INTRODUCTION: Based on Reason's model of human error, the Human Factors Analysis
and Classification System (HFACS) was developed as an analytical framework for
the investigation of the role of human error in aviation accidents. However,
there is little empirical work that formally describes numerically the
relationship between the levels and components in the model (the organizational
structures, psychological precursors of errors, and actual errors). METHOD: This
research analyzed 523 accidents in the Republic of China (ROC) Air Force between
1978 and 2002 through the application of the HFACS framework. RESULTS: The
results revealed several key relationships between errors at the operational
level and organizational inadequacies at both the immediately adjacent level
(preconditions for unsafe acts) and higher levels in the organization (unsafe
supervision and organizational influences). CONCLUSIONS: This research lends
support to Reason's model that suggests that active failures are promoted by
latent conditions in the organization. Fallible decisions in upper command levels
were found to directly affect supervisory practices, thereby creating
preconditions for unsafe acts, and hence indirectly impaired performance of
pilots, leading to accidents. The HFACS framework was proven to be a useful tool
for guiding accident investigations and developing accident prevention
strategies.
PMID- 17042252
TI - General aviation accidents in degraded visibility: a case control study of 72
accidents.
AB - BACKGROUND: Accidents in degraded visibility continue to account for a
disproportionately large number of fatal crashes and fatalities in general
aviation (GA). However, the relatively small percentage of these crashes annually
suggests that even a small reduction in the number of crashes can result in a
large reduction in associated fatalities. OBJECTIVE: This study identified risk
factors associated with GA accidents that occur in degraded visibility. METHODS:
Data collected during 72 National Transportation Safety Board investigations of
GA accidents were compared with data collected from 135 control flights matched
on weather conditions, location, time, and rules of flight. Study variables
included pilot demographics, experience, testing and accident histories, and the
purpose and length of flights. Initial comparisons were conducted using Chi
square analyses, followed by the development of a logistic regression model.
RESULTS: Univariate analyses identified significant differences in pilot age at
accident, age at initial certification, certificate level, instrument rating,
testing performance, and previous accident involvement. There were also
significant differences between groups related to aircraft ownership, purpose of
flight, and intended flight length. The logistic regression revealed significant
increased risk for pilots initially certified after age 25 [odds ratio (OR) 4.5,
95% confidence interval (CI) 1.9-10.81, without instrument ratings (OR 4.8, 95%
CI 1.8-12.8), with prior accidents/incidents (OR 3.1, 95% CI 1.1-8.7), and for
intended flights longer than 300 nmi (OR 4.6, 95% CI 1.6-13.8). CONCLUSIONS:
Certain risk factors (e.g., instrument rating) were consistent with previous
research, while others (e.g., age at certification) raise questions for future
research.
PMID- 17042253
TI - Gas nuclei, their origin, and their role in bubble formation.
AB - Gas bubbles are the primary agent in producing the pathogenic effects of
decompression sickness. Bubble formation during decompression is not simply the
consequence of inert gas supersaturation. Numerous experiments indicate that
bubbles originate as pre-existing gas nuclei. Radii are on the order of 1 microm
or less. Heterogeneous nucleation processes are involved in generating these gas
entities. Musculoskeletal activity could be the main promoter of gas nuclei from
stress-assisted nucleation. The half-life and faculty for nuclei to initiate
bubble formation during decompression depend on many factors. Oxygen window and
surface tension are involved in resolving bubbles. Two factors have been proposed
to stabilize gas nuclei against dissolution: gas nuclei trapped in hydrophobic
crevices and gas nuclei coated with surface-active molecules such as surfactants.
Diffusion and surface tension could play an important role in the formation of
gas nuclei crevices. However, while the concept of in vivo hydrophobic crevices
remains a theoretical possibility, none have yet been identified in tissues
and/or in microcapillaries. Moreover, while surfactants seem present in numerous
tissues and could play a role in gas nuclei stabilization, they could also be
involved in bubble elimination. The understanding of such mechanisms is of
primary importance to neutralize nuclei and for modeling bubble growth. Here we
present in a single document a summary of the original findings and views from
authors in this field.
PMID- 17042254
TI - In-flight medical incapacitation and impairment of airline pilots.
AB - Medical incapacitation in the cockpit is rare, although it is a concern that has
been the subject of several investigations over the years. With recent heightened
interest in this problem, it seemed worthwhile to review all relevant scientific
literature on the topic. Medline, PsychLit, the Aerospace Database, and other
online databases were searched for studies of pilot in-flight medical
incapacitation and impairment. The search revealed 13 articles during the years
from 1968 to 2000. The studies represented several different approaches and were
divided into five categories as follows: in-flight medical events, career
termination, simulator data, questionnaires, and epidemiological analysis. The
articles based on in-flight medical events showed that the leading causes of
those episodes were myocardial infarctions, cardiac arrhythmias, and epileptic
seizures. Few of the other types of studies used data from actual in-flight
medical occurrences, instead relying on indirect measures such as career
termination due to permanent medical grounding, loss of licensure insurance, or
general epidemiological data to estimate the frequency of in-flight medical
events. The reviewed studies provided only limited information on the frequency
and categories of in-flight medical events and did not include incapacitation
rates, making meaningful comparison between studies difficult. Future research
needs to be based on actual in-flight medical events, and should be normalized to
a useful denominator, such as flight time, to allow for meaningful comparison
between studies.
PMID- 17042255
TI - PET scan as an aid for the return of a head-injured aviator to flying duty.
AB - Head injury is not a rare event in aviators, and poses a difficult dilemma for
the flight surgeon regarding return to flying duty due to the fear of post
traumatic epilepsy. Positron emission tomography (PET) is a functional
neuroimaging modality that provides additional localizing data in epileptic
patients in the interictal phase. We describe a case of penetrating head trauma
with no loss of consciousness in a military jet fighter pilot in which the
magnetic resonance imaging revealed a minimal brain contusion. PET scan was used
as an additional tool for predicting the epileptogenic potential of this finding,
thus aiding the decision regarding the return of the aviator to flying duty.
PMID- 17042256
TI - PET scans and traumatic brain injuries: a brief comment.
PMID- 17042257
TI - Lunar exploration and the advancement of biomedical research: a physiologist's
view.
AB - Over the next few years, it will become apparent just how important lunar
exploration is to biomedical research and vice versa, and how critical both are
to the future of human spaceflight. NASA's Project Constellation should put a new
lunar-capable vehicle into service by 2014 that will rely on proven Space Shuttle
components and allow four astronauts to spend 7 d on the lunar surface. A modern
space transportation system opens up a unique opportunity in the space sciences-
the establishment of a permanent lunar laboratory for the physical and life
sciences. This commentary presents a rationale for focusing American efforts in
space on such a Moon base in order to promote understanding of the long-term
physiological effects of living on a planetary body outside the Van Allen belts.
PMID- 17042258
TI - Albrecht Ludwig Berblinger--inventor of the spring prosthesis and hang-glider
(1811).
AB - Albrecht Ludwig Berblinger (1770-1829), known as the "Flying Tailor of Ulm",
started with flight experiments in Ulm, Germany, in the early 19th century. He
gained experience in downhill gliding with a maneuverable airworthy semi-rigid
hang-glider and then attempted to cross the Danube River at Ulm's Eagle's Bastion
on the 31st of May 1811. The tricky local winds caused him to crash and he was
rescued by fishermen, making him the first survivor of a water immersion accident
of a heavier-than-air manned "flight machine". Though he failed in his attempt to
be the first man to fly, Berblinger can be regarded as one of the significant
aviation pioneers who applied the "heavier than air" principle and paved the way
for the more effective glide-flights of Otto Lilienthal (1891) and the Wright
Brothers (1902). Less known are Berblinger's significant contributions to the
construction of artificial limbs for medical use, as well as the spring
application in aviation. His invention of a special mechanical joint was also
used for the juncture of the wings of his "flying machine". Because of his
worthwhile contributions to medicine and flight, in 1993 the German Academy of
Aviation Medicine named an annual award for young scientists in the field of
aerospace medicine in his honor.
PMID- 17042259
TI - Posner-Schlossman syndrome and medical certification.
AB - Posner-Schlossman syndrome is a rare eye condition involving mild anterior
chamber inflammation and extreme intermittent intraocular pressure elevations.
Symptoms are mild and not incapacitating, but aviators need proper diagnosis and
treatment to ensure that visual acuity and visual fields are not affected.
PMID- 17042260
TI - You're the flight surgeon. Restless legs syndrome.
PMID- 17042261
TI - Cardiovascular tech trends.
PMID- 17042262
TI - [PH-sensitive cationic lipopeptides for the design of drug-delivery systems].
AB - Lipopeptides on the basis of L-glutamic acid and glutamine di- and monoesters
with aliphatic alcohols of various lengths that contain L-arginine, L-ornithine,
and L-lysine were synthesized. The behavior of these amphiphiles in aqueous
medium was shown to depend on their structure.
PMID- 17042263
TI - [Luliberin analogues exhibiting a cytotoxic effect on tumor cells in vitro].
AB - Luliberin analogues modified at the N-terminus were synthesized to search for
drugs exerting a cytotoxic effect on cells of hormone-dependent tumors. A
synthetic scheme effective in the preparation of analogues containing fatty acid
residues was proposed. The cytotoxic effect of the peptides was studied on a
number of cell lines of human tumors in vitro. The dependence of the antitumor
effect on the length of peptide chain, amino acid sequence, and structure of the
N-terminal group was demonstrated. Modification with palmitic acid was found to
result in highly active compounds in the case of analogues containing more than
ten aa, whereas modifications with lauric, caproic, or trimethylacetic acid led
to compounds with significantly lower activities. Analogues of luliberin
containing a palmitic acid residue and effectively inhibiting the growth of tumor
cells in vitro were synthesized.
PMID- 17042264
TI - [Spontaneous and promoted association of linear oligoglycines].
AB - Linear oligoglycines of various lengths bearing a carboxyl or an amide group at
their C-termini and also their poly(acrylamide) conjugates were synthesized. No
self-assembly into supramolecular structures was observed for free oligoglycines
H-(Gly)m-OH(m = 3-5). At the same time, oligoglycylamides H-(Gly)m-NH2 (m = 3-5)
demonstrated ability for both self-assembly in aqueous solution and assembly
promoted by an additional interaction with surface. In the case of polymer-bound
oligoglycines (and their amides), no intramolecular clustering of peptide chains,
as expected, was observed. This means that the presence of several oligoglycine
chains bound to each other in one center is not a necessary prerequisite for
polyglycine II-type association.
PMID- 17042266
TI - [Stabilization of glucoso-6-phosphate dehydrogenase by its substrate and cofactor
in an ultrasonic field].
AB - The inactivation kinetics of glucoso-6-phosphate dehydrogenase (GPDH) and its
complexes with glucoso-6-phosphate and NADP+ was characterized in aqueous
solutions at 36-47 degrees C under treatment with low frequency (27 kHz, 60
W/cm2) and high frequency ultrasound (880 kHz, 1 W/cm2). To this end, we measured
three effective first-order inactivation rate constants: thermal k(in)* , total
(thermal and ultrasonic) kin, and ultrasonic kin (US). The values of the
constants were found to be higher for the free enzyme than for its complexes GP
DH-GP and GPDH-NADP+ at all temperatures, which confirms the enzyme stabilization
by its substrate and cofactor under both thermal and ultrasonic inactivation.
Effective values of the activation energies (Ea) were determined and the
preexponential factors of the rate constants and thermodynamic activation
parameters of inactivation processes (deltaH*, deltaS*, and deltaG*) were
calculated from the temperature dependences of the inactivation rate constants of
GPDH and its complexes. The sonication of aqueous solutions of free GPDH and its
complexes was accompanied by a reduction of Ea and deltaH* values in comparison
with the corresponding values for thermal inactivation. The Ea, deltaH*, and
deltaS* inactivation values for GPDH are lower than the corresponding values for
its complexes. A linear dependence between the growth of the deltaH* and deltaS*
values was observed for all the inactivation processes for free GPDH and its
complexes.
PMID- 17042265
TI - [Stress-protective effect of the synthetic ACTH-like peptide leucocorticotropin].
AB - We found that the tritium-labeled synthetic ACTH-like octapeptide
leucocorticotropin corresponding to the 81-88 sequence of the precursor of human
interleukin-1alpha ([3H]GKVLKKRR) is bound by the ACTH receptor of rat adrenal
cortex with a high affinity and specificity (Kd 2.2 +/- 0.1 nM). This peptide was
shown to exert no effect on the adenylate cyclase activity of the membranes of
rat adrenal cortex in the concentration range from 1 to 1000 nM.
Leucocorticotropin administration three times at doses of 10-20 microg/animal did
not change the level of hydroxycorticosteroids (11-HOCS) in the rat adrenal
glands in the absence of temperature action. At the same time, the peptide
abolishes (at a dose of 20 microg/animal, three times) or significantly decreases
(at a dose of 10 microg/animal, three times) the dramatic increase in the 11-HOCS
content in the adrenal glands occurring in the case of cold or heat shock. Thus,
leucocorticotropin normalizes the 11-HOCS level in the rat adrenal cortex during
stress. The stress-protective effect of the peptide is mediated through the ACTH
receptor.
PMID- 17042267
TI - [Compaction of single supercoiled DNA molecules adsorbed onto amino mica].
AB - A model of possible conformational transitions of supercoiled DNA in vitro in the
absence of proteins under the conditions of increasing degree of compaction was
developed. A 3993-bp pGEMEX supercoiled DNA immobilized on various substrates
(freshly cleaved mica, standard amino mica, and modified amino mica with a
hydrophobicity higher than that of standard amino mica) was visualized by atomic
force microscopy in air. On the modified amino mica, which has an increased
density of surface positive charges, single molecules with an extremely high
degree of compaction were visualized in addition to plectonemic DNA molecules. As
the degree of DNA supercoiling increased, the length of the first-order
superhelical axis of molecules decreased from 570 to 370 nm, followed by the
formation of second- and third-order superhelical axes about 280 and 140 nm long,
respectively. The compaction of molecules ends with the formation of minitoroids
about 50 nm in diameter and molecules of spherical shape. It was shown that the
compaction of single supercoiled DNA molecules immobilized on amino mica to the
level of minitoroids and spheroids is due to the shielding of mutually repulsing
negatively charged phosphate groups of DNA by positively charged amino groups of
the amino mica, which has a high charge density of its surface.
PMID- 17042268
TI - [Functionalized nanocomposite coating of a glass surface for oligonucleotide
immobilization].
AB - A new type of coating for manufacturing DNA chips was constructed of the basis of
an organic-inorganic nanocomposite based on the polyvinylbutyral
tetraethoxysilane copolymer. The organosilicon composite was functionalized by
introduction of ethanolamine vinyl ether copolymers, which contain amino groups
and anchor vinyloxide units capable of reacting with silanol groups of the
nanocomposite. The resulting coatings form a film on glass slides with a high
surface density of amino groups (up to 700 groups/nm2) suitable for three
dimensional immobilization of oligonucleotides. The use of bifunctional reagents
(e.g., phenylene diisothiocyanate) for the attachment of oligonucleotides bearing
amino linkers to the amino-containing surface provides an immobilization density
of 0.5-1.6 pmol/mm2. Immobilization with a higher density (10-12 pmol/mm2) was
achieved for attachment to amino-containing glass slides upon the use of
oligonucleotides containing selectively activated terminal phosphate groups. The
activation of oligonucleotides was carried out with the triphenylphosphine
dithiodipyridine pair in the presence of dimethylaminopyridine N-oxide. The
resulting DNA chips were shown to be useful in principle for DNA detection.
PMID- 17042269
TI - [Glycosylation of 5-Phenyl-1,3,4-oxadiazole-2-thiol with alpha-D-glucopyranosyl
chloride under phase transfer conditions].
AB - 5-Phenyl-1,3,4-oxadiazole-2-thiol is glycosylated easily and in high yields with
2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-alpha-D-glucopyranosyl chloride in the
presence of catalytic amounts of aliphatic and aromatic crown ethers under phase
transfer (solid-organic solvent) conditions. The reaction rate and the ratio of
the resulting N- and S-regioisomers depend on the catalyst nature.
PMID- 17042270
TI - [Chemical modification of heparin].
AB - Heparin was modified at carboxyl groups by reaction with several
pharmacologically important amino-containing compounds in aqueous medium in the
presence of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide. In dependence on the
nature of the amine and the ratio of reagents, conjugates containing 36-100%
amide and 0-25% isoureidocarbonyl groups were synthesized. Isoureidoarylamide
groups are present, along with amide moieties, in the products of heparin
modification by hydroxyl-containing aromatic amines. The conjugate of heparin
with p-aminobenzoic acid contained oligomeric arylamide.
PMID- 17042271
TI - [Identification and structural analysis of a glycophospholipid component from the
venom of ant Paraponera clavata].
AB - The venom of South American ant Paraponera clavata and its low-molecular-mass
fraction were shown to possess insectotoxic and pore-forming activities. A number
of glycophospholipid components were isolated from this ant venom by means of gel
filtration and reversed-phase chromatography. Some of the compounds cause
conductivity fluctuations in lipid bilayer membranes within the ranges 3-25 pS
and 200-400 pS at concentrations of 10(-6) to 10(-7) M. N-Acetylglucosamine, a
fatty acid, and phosphoric acid residues were found in their structures. A full
structure, 3-myristoyl-2-acetamido-2-deoxy-alpha-D-glucopyranosyl phosphate, was
elucidated for one of the compounds by the use of 1H, 13C, and 31P NMR
spectroscopy and mass spectrometry.
PMID- 17042272
TI - [An unusual lipid A from a marine bacterium Chryseobacterium scophtalmum CIP
104199T].
AB - The hydrolysis of defatted cells of the marine bacterium Chryseobacterium
scophtalmum CIP 104199T with 10% acetic acid (3 h, 100 degrees C) led to an
unusual lipid A (LA) (yield 0.6%), obtained for the first time. Using chemical
analysis, FAB MS, and NMR spectroscopy, it was shown to be D-glucosamine 1
phosphate acylated with (R)-3-hydroxy-15-methylhexadecanoic and (R)-3-hydroxy-13
methyltetradecanoic acids at the C2 and C3 atoms, respectively. It is similar to
the monosaccharide biosynthetic precursor of lipopolysaccharide (LPS), so-called
lipid X (LX). Unlike LX, LA can be isolated by the treatment of bacteria with
organic solvents only after the preliminary acidic hydrolysis of the cells, which
suggests that LA might be strongly, probably chemically, linked to other
components of the outer membrane. However, LPS cannot be such a component,
because extraction with phenol-water or phenol-chloroform-petroleum ether
mixtures in high yields (5.34% and 0.5%, respectively) leads to preparations that
do not contain 3-deoxy-D-manno-oct-2-ulopyranosonic acid, 3-hydroxyalkanoic
acids, or LA.
PMID- 17042273
TI - [Synthesis of thio- and selenophospholipids from 2,2,5,5
tetra(hydroxymethyl)cyclopentanone].
AB - New phospholipids, thio- and selenoanalogues of phosphatidic acids, were
synthesized on the basis of 2,2,5,5-tetra(hydroxymethyl)cyclopentanone. The
starting tetraol monoketal was phosphorylated with amidophosphorous acid
chlorides to protected polyol amidophosphites, which were further sulfurized or
selenized to phosphoacetals. These were directly acylated with fatty acid
chlorides to thio- and selenoanalogues of phospholipids.
PMID- 17042274
TI - [Delta5-7-Ketosterols with modified side chain: the synthesis and the effects on
viability and cholesterol biosynthesis in Hep G2 cells].
AB - (22E)-3beta-Hydroxysitosta-5,22-dien-7-one, (22R, 23R)-3beta,22,23
trihydroxysitost-5-en-7-one, and (22R, 23R)-3beta-hydroxy-22,23
isopropylidenedioxysitost-5-en-7-one were synthesized. The cytotoxicity and
effects on cholesterol biosynthesis of the resulting 7-ketosterols, 7
ketocholesterol, and (22S,23S)-3beta-hydroxy-22,23-oxidositost-5-en-7-one were
studied in hepatoblastoma Hep G2 cells.
PMID- 17042275
TI - [Synthesis of ethriolophospholipids of acetal type].
AB - New analogues of acetal-type phospholipids were obtained on the basis of ethriol
(2-hydroxymethyl-2-ethyl-1,3-propanediol). The starting triol originally was
condensed with decanal or dodecanal to form acetals, which were then
phosphorylated with tetraethyldiamidophosphorous acid chloride. The
amidophosphites were further oxidized with iodosobenzene or sulfurized to the
corresponding acetal-type phospholipids and their thio analogues.
PMID- 17042276
TI - [The symbiotic microflora associated with the tegument of proteocephalidean
cestodes and the intestines of their fish hosts].
AB - The indigenous symbiotic microflora associated with the tegument of
proteocephalidean cestodes and the intestines of their fish hosts has been
investigated in morphological and ecological aspects. The indigenous microflora
associated with the cestode tegument consists of the nannobacteria population,
which was present obligatorily on the surface of tegument, and the "deep
microflora". The deep microflora associates with some few species of parasites
only. Each individual host-parasite micro-biocenosis includes specific indigenous
symbiotic microorganisms, with the differing microfloras of host intestine and
parasite. Physiology, biochemistry and/or diet of hosts apparently influence on
the symbiotic microflora's structure of parasites. The least bacteria abundance
and diversity of their morphotypes were observed in the parasites from baby
fishes. The diversity and abundance of bacteria were increased with the fish host
ageing and the formation of the definitive structure of its intestine. It is an
evidence of the gradual invading of the intestinal parasites (cestodes) tegument
by bacterial cells. The invading is realized on the base of the microflora that
was present in the food of fish host. The symbiotic microflora has specific
morphological features, can regulate the homeostasis of the cestodes and fish
hosts and also can maintain equilibrium of alimentary and immune interrelations
in the host-parasite system.
PMID- 17042277
TI - [Taxonomic diversity of parasites from agnathans and fishes in the Volga basin.
II. Parasitic Coelenterata and Monogenea].
AB - A checklist of the Monogeneans and Coelenterates parasitizing fishes in the Volga
River basin is given. The list of hosts with the data on their occurrence in
different areas of the Volga River basin is provided for each parasite species.
The data on the parasites from 46 fish species are presented. The checklist
includes 139 species and 6 taxa of subspecific rank. 9 species (Dactylogyrus
aristichthys, D. ctenopharyngodonis, D. hypophthalmichthys, D. lamellatus, D.
nobilis, D. suchengtaii, Pseudodactylogyrus bini, P. microrchis, and Eudiplozoon
nipponicum) were introduced into the Volga River basin accidentally together with
the Far Eastern fish species during the process of their naturalization.
PMID- 17042278
TI - [Dracunculoid nematodes (Spirurida: Dracunculoidea) of fishes from the Volga
River delta].
AB - Faunistic and some morphological data, as well as nomenclature notes on
dracunculoid nematodes parasitising fishes in the Volga River delta, are
presented. The author replaced a preoccupied generic name Molnaria Moravec, 1968
(Skrjabillanidae) by the new name Kalmanmolnaria nom. nov. The validity of
Philometroides lusii (Vismanis, 1962) comb. nov. as a senior objective synonym of
Philometroides lusiana (Vismanis, 1967) Ivaschkin et al., 1971 is restored.
PMID- 17042279
TI - [Morphofunctional changes in the midgut of the Ixodes females (Acari: Ixodidae)
during the immunizing feedings].
AB - The changes of the midgut in the females of the tick species Ixodes persulcatus
and I. ricinus during the second and third immunizing feeding on rabbits were
studied by the histological technics. The alternation of one generation of the
digestive cells of nymphal stage and two generations of the digestive cells of
adult stage was observed. The generation of secretory cells is absent. The tick
completes feeding and drop off when the last generation of the digestive cells is
on the initial activity stages. The amount of the blood consumed is not enough
for the rhythmical functioning of the midgut. The feeding of tick is broken on
the second phase and full satiation does not take place. It is apparently an
effect of the interruption of the blood entrance into the midgut cavity of
feeding tick as a probable result of anti-ticks resistance of unnatural hosts.
PMID- 17042280
TI - [Spatial and temporal structure of the infectious diseases incidence in the
population of the south of the Russian Far East: system approach].
AB - New conception of the anthropo-parasitic system has been elaborated. Spatial and
temporal structure of the infections diseases incidence in the Primorye Territory
has been analysed on the base of this conception.
PMID- 17042281
TI - [The longevity of the tick Ixodes ricinus (Acari: Ixodidae) in Central Russia].
AB - The longevity of the tick Ixodes ricinus has been studied on 27 samples from a
wild population of the Moscow Region. Ticks were kept in small cages and glass
tubes under conditions close to natural. About 2/3 of the specimens collected in
spring survived till the next spring and later died out gradually during the
second season of their activity. Very few specimens reached the beginning of the
third winter in their life, but apparently none of them survived the end of the
winter. The life span of males was the same as that of females. No mass
activation of adult ticks was recorded in the autumn of the year of their
molting. It seems that the rise of the autumnal density of adult ticks depends
mainly on the increased activity of the females which molted from nymphs last
year.
PMID- 17042282
TI - [The abundance and distribution of the Ixodes persulcatus (Acari: Ixodidae) near
its northern spreading limit in the Ural Mountains].
AB - A count of the tick species Ixodes persulcatus Schulze, 1930 was carried out in
the "Denezhkin Kamen" Nature Reserve and adjacent territories (the Severoural'sk
and Ivdel' Districts of the Sverdlovsk Region, the Northern Urals geographical
province) in the 2005. The abundance and distribution of unengorged adults has
been evaluated on an area of 22.5 square kilometers (N 60 degrees 27'-60 degrees
30' E 059 degrees 38'-059 degrees 42'). The area includes proportionally main
landscape and vegetation elements of the region studied, from mountain analogues
of the middle and northern taiga up to tundra. One tick species, I. persulcatus,
has been collected by flagging with the abundance from 0.4 up to 6.8 (average 1.6
+/- 0.9) specimens per flag-hour. The observed values of abundance are classified
into three classes (I - ticks are absent, II - 1-2 specimens, and III - 3-7
specimens per flag-hour). The class I amounts 20, II - 75, and III - 5% of the
area examined. It has been revealed by the expert evaluation of the 2003-2004 and
counts of the 2005 that ticks occur stably in the Northern Ural, reaching N 61
degrees and 400 m above sea level. The level of the species abundance remained
constant till the middle of summer. In this period the activity of ticks
dependent on the weather optimum only.
PMID- 17042283
TI - EMRs and quality improvement in patient care.
PMID- 17042284
TI - How to choose an electronic medical record.
AB - I chose a Windows-based file system over a server-based system with a proprietary
database, or a web-based system which has both a proprietary database and which
also required a full time Internet connection. My reasoning was that I found it
uncomplicated. I was familiar with the Windows interface and it required little
effort to enter my existing data and was simple to operate the system. If one
laptop crashes, my other computers still work. I don't fear failure of an
Internet connection source, a modem or a server, power surges or other possible
single points of failure that might prevent my patient care. I can incorporate
all document types, I can update jump drives with any needed medical information.
I can share information instantly with other systems. I can store my own data in
a flexible and open format. I have no maintenance contract and I can make changes
in my system or can even change vendors at any time. Last but certainly not
least, I do not need a highly trained technical staff to operate or maintain our
system.
PMID- 17042285
TI - Electronic medical records delivers quality and efficiency to small practice.
PMID- 17042286
TI - Pediatric practice selects program designed by pediatrician.
PMID- 17042287
TI - Embracing change leads to improving patient care.
PMID- 17042288
TI - Using electronic medical records in the 21st century.
PMID- 17042290
TI - Medicine weathers challenging legislative session.
PMID- 17042289
TI - EMR decision time: your Rx for success.
PMID- 17042291
TI - CDC's Advisory Committee recommends human papillomavirus virus vaccination.
PMID- 17042292
TI - Legal implications of the electronic medical record in Georgia.
PMID- 17042293
TI - Physician be wary: the status of employment restrictive covenants in Georgia.
PMID- 17042294
TI - The 15th hole.
PMID- 17042295
TI - Hard work.
PMID- 17042296
TI - How on earth did this happen?
PMID- 17042297
TI - Nursing home medical director: revised CMS guidelines emphasize leadership.
PMID- 17042298
TI - Now hiring! Arkansas, like the nation, faces imminent health care worker
shortages.
PMID- 17042299
TI - Pericarditis: guidelines and management.
PMID- 17042300
TI - Cardiac transplantation at Arkansas Children's Hospital.
AB - Cardiac transplantation in children has evolved over the past 20 years. In 1990
Arkansas Children's Hospital (ACH) developed a Cardiac Transplant Program as part
of its tertiary care of patients with congenital and acquired heart disease. The
program evolved into a regional pediatric referral program and is now one of the
busiest in the United States. "Bridging" to transplant increased the number of
patients surviving long enough to receive a donor heart. This article reviews the
historical perspective of pediatric cardiac transplant along with the development
and current state of the program at Arkansas Children's Hospital.
PMID- 17042301
TI - Now and then: the progress of care.
PMID- 17042302
TI - Oxygen administration: is practice based on evidence?
AB - An audit of oxygen administration to children in the paediatric unit of a
district general hospital was carried out following the introduction of new
guidelines. The aim of the audit was to review oxygen administration practices
against the guidance but also to gather information concerning patients,
diagnoses, prescription practices and delivery devices. The notes of 36 infants
and children admitted during a two week (winter) period who received oxygen were
retrospectively reviewed for the audit. The standards for monitoring the amount
of oxygen delivered and oxygenation were found to be high but the prescribing of
oxygen was varied. The most common diagnosis of children receiving oxygen was
bronchiolitis, and the device used to deliver oxygen most frequently was nasal
cannula. Few headboxes were used and experienced team members noted this as a
marked change in practice. A further examination of the evidence on the use of
nasal cannulae for oxygen delivery in the younger age group led to new practice
recommendations.
PMID- 17042303
TI - Sex education in school: young people's views.
AB - The aims of this study were to explore adolescents' levels of knowledge on sexual
health issues and their views on the sex education they receive as part of their
compulsory education. Twenty students from two schools completed a short
questionnaire and participated in a focus group discussion. The students had an
excellent level of knowledge about sexual health issues, which contradicts
Government views that ignorance is the key to adolescents' sexual health concerns
(Social Exclusion Unit 1999). Participants felt their sex education was 'too
little, too late' and that it should be taught by someone other than a teacher.
Sex education should be introduced earlier in the curriculum as well as finding
an acceptable 'teacher' if adolescent sexual health is to improve.
PMID- 17042304
TI - Breast feeding and society.
AB - Britain has the lowest breastfeeding rate of all countries in Europe; it is no
longer the cultural norm in our society. Breastfeeding rates are affected by
public attitude. This state of affairs is partly because of society's views on
breastfeeding mothers, even though breastfeeding is known to be the optimum
method of infant feeding for the baby, family and society. Common themes in the
literature and websites are the economic advantages of breastfeeding, the public
health benefits and the social construct of breastfeeding. Paediatric nurses have
an important role in supporting breastfeeding mothers so that they are able to
continue breastfeeding.
PMID- 17042305
TI - Outreach: making a difference in family life.
PMID- 17042306
TI - Improving links between CAMHS and primary care.
AB - Only a small percentage of children and young people with mental health problems
reach child and adolescent mental health services (CAMHS) (Young Minds 2003).
Government policy, voluntary organisation reports and research all support the
need for improved links and open communication between health services in order
to address the mental health needs of children and young people.
PMID- 17042307
TI - Wound management.
PMID- 17042308
TI - Inhaled nitrous oxide during painful procedures: a satisfaction survey.
AB - Children with cystic fibrosis (CF) undergo repeated invasive medical procedures.
This article summarises a survey of the use of nitrous oxide to minimise the
psychological trauma and pain that was undertaken within the paediatric unit of a
district general hospital (Williams et al 2004). Pain levels pre and post
procedure, whether the treatment was effective, any adverse effects and comments
by children and carers were recorded. Nitrous oxide was safe and effective in
reducing pain, trauma and 'needle phobia'. It is now being offered to other
children in the management of procedural pain.
PMID- 17042309
TI - Negotiation of care by children's nurses: lessons from research.
AB - Parental participation and role negotiation are central elements in family
centred care, but research suggests that such negotiation tends to be ad hoc,
depending on the relationships developing between the family and health
professionals. Lack of effective communication, professional expectations and
issues of power and control often prevent open and mutual negotiation between
families and health professionals, especially nurses. This article summarises key
lessons from a critical review of relevant research literature (Corlett and
Twycross 2006) which suggests that nursing staff often control parental
participation leaving parents feeling disempowered and deskilled. Poor
communication and lack of information sharing exacerbate the situation. Where
parents do not comply with nurses' expectations conflict can arise, resulting in
more anxiety for already stressed parents. Current health policy requires that
health workers listen to children and their families, to actively involve them in
the decision-making process and to plan care around their needs and wishes.
Nurses need to be aware of the way they interact with parents and the control
they may unwittingly exert. A greater emphasis on communication, interpersonal
and negotiation skills within nurse education is also needed.
PMID- 17042310
TI - Developing rigour in observation of the sick child: Part 1.
AB - This is the first of a five part series focused on the continuing professional
development of rigour in observation of the sick child. Part 1 provides an in
depth analysis of basic principles underpinning observation generally. Parts 2 to
5 will provide in-depth analyses of specific nursing observations.
PMID- 17042311
TI - A picture of the United Kingdom using the National Statistics Socio-economic
classification.
AB - This article describes the socio-economic characteristics of working age people
in the United Kingdom in 2005 based on the National Statistics Socio-economic
Classification. The population is described by NS-SEC and gender, age-group,
region or household type.
PMID- 17042312
TI - Introducing the area classification of output areas.
AB - This article provides a brief introduction to the Area Classification of Output
Areas. The classification uses data from the 2001 Census to group the 223,060
output areas into groups of similarity based on their census attributes. The
classification is freely available as a 'National Statistic' via the National
Statistics website.
PMID- 17042313
TI - Methodology used for producing ONS's small area population estimates.
AB - The Office for National Statistics (ONS) has set up a project to investigate the
feasibility of producing postcensal small area population estimates on a
nationally consistent basis for England and Wales. Following on from earlier
investigations to identify potential data sources and methods, ward and Super
Output Area population estimates have been released as 'experimental statistics'.
This article covers the methodology used to produce these estimates, feedback
from user consultation with the initial estimates released at ward level, summary
statistics on the population estimates for mid-2001 to mid-2003, and future
developments for small area population estimates.
PMID- 17042314
TI - An international comparative study on the use of the Cohort Component Method for
estimating national populations.
AB - This comparative study explores the use of the Cohort Component Method (CCM) to
produce national level population estimates. This method is used annually to
calculate mid-year population estimates for England and Wales by the Office for
National Statistics (ONS). Initially the article considers recent population
change in England and Wales, with particular emphasis on the growing importance
and challenges faced by migration estimation. Comparisons are then made between
how population estimates are produced in England and Wales and other countries,
with a particular focus on differences in the way the CCM is applied. Recent
changes in methods used to estimate population are then reviewed along with a
discussion of alternative approaches such as those described in academic
literature.
PMID- 17042315
TI - Report: Joint ESRC/ONS/BSPS public policy seminar series on the implications of
demograhic change.
PMID- 17042316
TI - Living the legacy of 'Mother Seacole'.
PMID- 17042318
TI - An informative day.
PMID- 17042317
TI - The NHS pension scheme review--existing members.
PMID- 17042319
TI - The contribution of patients and the public to the NICE guideline.
PMID- 17042320
TI - A question of influence.
PMID- 17042321
TI - Medicines in maternal and neonatal care.
PMID- 17042322
TI - Consultation on NMC changes.
PMID- 17042323
TI - A time of independence.
PMID- 17042324
TI - A double act: implementing the National Service Framework.
PMID- 17042325
TI - Awareness of von Willebrand's.
PMID- 17042326
TI - Did the recent media coverage of the healthcare commission report accurately
portray to the public, the profession and the role of the midwife?
PMID- 17042327
TI - Synergistic combination effect of cidofovir and idoxuridine on vaccinia virus
replication.
AB - In view of the potential menace of a terrorism attack with smallpox virus, an
intensive search of chemotherapeutic agents active against orthopoxviruses is
underway. We comparatively studied the antiviral activity of cidofovir (CDV) and
idoxuridine (IUdR) against two vaccinia virus (VV) strains, Bratislava and RIIPD,
in cell cultures of chick embryo fibroblasts (CEF). The investigations were
carried out according to cytopathic effect (CPE) inhibition assay protocols. To
determine the cytotoxicity of the compounds, maximal tolerated concentration
(MTC) was calculated in CEF cell monolayers and 50% cell growth inhibitory
concentration (CGIC50) was calculated in growing cell cultures. It was found that
the antiviral effects were strongly dependent on virus inoculum size. There were
no marked differences in the susceptibility to CDV and IUdR between the two VV
strains. The individual half maximal inhibitory concentration (IC50) for CDV
varied from 7.1-8.5 microM at 10/100 virus 50% infectious dose (ID50) to 13.6
26.5 microM at 10,000 ID50. The CDV selectivity index was also virus dose
dependent with MTC/IC50 and CGIC50/IC50 values ranging between 37.8-141.4 and
33.3-124.6, respectively. For IUdR, IC50 ranged from 0.58 to 0.85 microM, but the
selectivity index for monolayer CEF and growing cell cultures produced
substantial different results with MTC/IC50 and CGIC50/IC50 values between 117.7
172.4 and 20.4-33.3, respectively. The combination effects of CDV and IUdR
against VV Bratislava strain in the CPE inhibition test were also determined. The
test design of both combination antiviral effect and combined cytotoxicity
followed a three-dimensional model. The combined effect of CDV and IUdR on VV
replication in monolayer CEF cultures was characterized as a markedly synergistic
one. In contrast, CDV and IUdR together reduced cytotoxicity in both monolayer
and growing CEF cells.
PMID- 17042328
TI - Indolyl aryl sulphones as HIV-1 non-nucleoside reverse transcriptase inhibitors:
synthesis, biological evaluation and binding mode studies of new derivatives at
indole-2-carboxamide.
AB - New non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are active
against the commonly occurring mutations of HIV are urgently needed for the
treatment of AIDS. We synthesized new NNRTIs of the indolyl aryl sulphone (IAS)
family, which are endowed with high antiviral potency against HIV-1 wt (wild
type), and the Y181C and K103N-Y181C drug resistant mutant strains. Several new
compounds were highly active in lymphocytes infected with primary isolates
carrying the K103N-V1081-M184V and L1001-V1081 mutations. The design of new IASs
was based on three-dimensional quantitative structure-activity relationship (3D
QSAR) studies and docking simulations. A cross-docking study was also undertaken
to gain some insights in to the binding mode of the newly synthesized IASs in the
wt and mutated isoforms of reverse transcriptase.
PMID- 17042329
TI - Inhibition of hepatitis C replicon RNA synthesis by beta-D-2'-deoxy-2'-fluoro-2'
C-methylcytidine: a specific inhibitor of hepatitis C virus replication.
AB - beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) is a cytidine analogue
with potent and selective anti-hepatitis C virus (HCV) activity in the subgenomic
HCV replicon assay, 90% effective concentration (EC90)=4.6 +/- 2.0 microM. The
spectrum of activity and cytotoxicity profile of PSI-6130 was evaluated against a
diverse panel of viruses and cell types, and against two additional HCV-1b
replicons. The S282T mutation, which confers resistance to 2'-C-methyl adenosine
and other 2'-methylated nucleosides, showed only a 6.5-fold increase in EC90.
When assayed for activity against bovine diarrhoea virus (BVDV), which is
typically used as a surrogate assay to identify compounds active against HCV, PSI
6130 showed no anti-BVDV activity. Weak antiviral activity was noted against
other flaviviruses, including West Nile virus, Dengue type 2, and yellow fever
virus. These results indicate that PSI-6130 is a specific inhibitor of HCV. PSI
6130 showed little or no cytotoxicity against various cell types, including human
peripheral blood mononuclear and human bone marrow progenitor cells. No
mitochondrial toxicity was observed with PSI-6130. The reduced activity against
the RdRp S282T mutant suggests that PSI-6130 is an inhibitor of replicon RNA
synthesis. Finally, the no-effect dose for mice treated intraperitoneally with
PSI-6130 for six consecutive days was > or =100 mg/kg per day.
PMID- 17042330
TI - Synthesis and antiviral evaluation of alkoxyalkyl esters of
phosphonopropoxymethyl-guanine and phosphonopropoxymethyl-diaminopurine.
AB - Phosphonopropoxymethyl-guanine is the methylene phosphonate analogue of
acyclovir. Although not highly active against HSV, 4-38 microM of
phosphonopropoxymethyl-guanine has been reported to be active against human and
murine cytomegalovirus. Recently we found that cidofovir, when esterified with
alkoxyalkyl moieties, showed greatly increased antiviral activity against
cytomegalovirus, herpes simplex virus and orthopoxviruses, in vitro. The
alkoxyalkyl esters of cidofovir are orally active in murine models of human and
murine cytomegalovirus and orthopoxviruses in vivo. To see if the antiviral
activity of phosphonopropoxymethyl-guanine, phosphonopropoxymethyl-diaminopurine
and phosphonopropoxymethyl-N6-cyclopropyl-diaminopurine could be increased by
this approach, we synthesized their hexadecyloxypropyl- and octadecyloxyethyl-
esters and evaluated antiviral activity and cytotoxicity in cells infected with
HSV-1 and HCMV, in vitro. Marked increases in antiviral activity were noted in
the alkoxyalkyl esters of phosphonopropoxymethyl-guanine. Alkoxyalkyl esters of
diaminopurine and N6-cyclopropyl-diaminopurine showed slight increases in
activity against HSV-1 and marked increases in activity against HCMV. The results
suggest that esterification with alkoxyalkyl moieties may be a generally useful
way to increase antiviral activity of nucleoside phosphonates.
PMID- 17042331
TI - Anti-herpes simplex virus activities of two novel disulphated cyclitols.
AB - By screening a library of sulphated compounds of low molecular weight, we have
found that several cyclitol derivatives, each modified with two sulphate groups
in addition to pyrrole and various aromatic moieties, inhibited infectivity of
herpes simplex virus (HSV) at concentrations approximately 100 times lower than
those toxic for cultured cells. These disulphated cyclitols interfered with HSV-1
attachment to cells, and efficiently reduced the cell-to-cell spread of the
virus. This effect is most likely due to their low molecular weight and
associated with the compounds' capability to access the narrow intercellular
spaces. Furthermore, these disulphated cyclitols also inactivated infectivity of
HSV. However, the virus-inactivating activities of these compounds were to some
extent diminished in the presence of human cervical secretions or other protein
rich solutions suggesting that disulphated cyclitols may have some features of
surfactant-type virucides. In conclusion, this new class of anti-HSV compounds
offers potential for further development.
PMID- 17042332
TI - Short communication inhibitory activity of 4-[(1,2-dihydro-2-oxo-3H-indol-3
ylidene)amino]-N-(4,6-dimethylpyrimidin-2-yl) benzenesulphonamide and its
derivatives against orthopoxvirus replication in vitro.
AB - 4-[(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)amino]-N-(4,6-dimethylpyrimidin-2-yl)
benzenesulphonamide and its derivatives were tested in vitro for antiviral
activity against vaccinia and cowpox virus replication in human foreskin
fibroblast (HFF) cells, and their activity was compared with cidofovir (CDV).
Among the tested compounds, 4-[(5-methyl-1,2-dihydro-2-oxo-3-H-indol-3
ylidene)amino]-N-(4,6-dimethylpyrimidin-2-yl)benzene-sulphonamide was the most
active against vaccinia virus, with a 50% effective concentration (EC50) value of
18 microM and 4-[(N-acetyl-1,2-dihydro-2-oxo-3-H-indol-3-ylidene)amino]-N-(4,6
dimethylpyrimidin-2-yl) benzenesulphonamide was the most active against cowpox
virus (EC50=33 microM). Cidofovir was found to have an EC50 of 20 microM and 32
microM against vaccinia and cowpox virus, respectively. Most of the tested
compounds were non-cytotoxic (>300 microM) in HFF cells as determined by a
neutral red uptake assay. The substitution of a halogen atom at the 5-position of
isatin abolished the antiviral activity.
PMID- 17042333
TI - Are we ready for a flu pandemic?
PMID- 17042334
TI - "It's easy to be lured into nursing but I'm not sure I'd recommend it".
PMID- 17042335
TI - 'Medicines management is not just a pharmacy issue'.
PMID- 17042336
TI - Why we must stop needlestick injuries.
PMID- 17042338
TI - The use of human tissue in bone grafting techniques.
AB - The Medicines and Healthcare products Regulatory Agency has informed hospitals in
England and Wales that bone graft material, which may include bone obtained
illegally without consent, may have been implanted into a small number of UK
patients. This article outlines the technique of bone grafting, examines the
normal regulation and safety considerations and highlights the nursing
implications surrounding this issue.
PMID- 17042337
TI - Living life to the full. Interview by Clare Lomas.
PMID- 17042339
TI - The urinary system. Part 1--introduction.
PMID- 17042340
TI - Cancer genetics: the importance of obtaining a family history.
AB - Cancer genetics is a rapidly evolving field that is becoming an integral part of
a cancer patient's care. Until recently little genetics had been taught in the
nursing curricula but a recent drive by the Department of Health is resulting in
the integration of genetics into nurse training.
PMID- 17042341
TI - Using a virtual care scenario to enhance student learning.
AB - A series of care scenarios were developed entitled 'eWARD' that complement
traditional teaching methods employed in the education of nursing students. This
article discusses the development of one of these scenarios, which was based on a
stroke rehabilitation theme, in relation to its theoretical underpinnings as well
as its implementation and evaluation.
PMID- 17042343
TI - Stars in their files.
PMID- 17042344
TI - Food for thought.
PMID- 17042345
TI - Specialist nursing under threat.
PMID- 17042346
TI - Australia prioritises dementia.
PMID- 17042347
TI - Healthy, wealthy and old?
PMID- 17042348
TI - Shingles: relief at last.
PMID- 17042349
TI - Future perfect or imperfect?
PMID- 17042350
TI - Mental health and functional mental disorder in older adults.
AB - The available literature on mental health and older people tends to focus on
dementia rather than functional illness, despite the greater prevalence of the
latter. This review analyses articles published on mental health in nursing
journals and considers their content. The author suggests that those working with
older adults need to hear more about the experiences of those who suffer with
mental health problems.
PMID- 17042351
TI - Introducing the Liverpool Care Pathway into nursing homes.
AB - Around half a million older people aged 65 or over live in care homes across the
UK and substantial numbers end their lives in these care settings. The Liverpool
Care Pathway for the dying patient (LCP) was developed to transfer the hospice
model of care into other care settings. This paper describes a pilot project to
introduce the LCP into care homes local to the Queen Mary's Sidcup NHS Trust with
a view to reducing the number of very ill elderly patients who are transferred to
the acute trust from care homes and then die in A&E.
PMID- 17042352
TI - Eva's view.
PMID- 17042353
TI - Our health, our care, our say.
PMID- 17042354
TI - Putting safety first.
PMID- 17042355
TI - Carol Baxter.
PMID- 17042356
TI - Knowledge management essential, not optional.
PMID- 17042357
TI - Learning differently: e-learning in nurse education.
PMID- 17042358
TI - Patient empowerment: myth or reality?
PMID- 17042359
TI - Spirituality and health.
PMID- 17042360
TI - Quality assurance of NHS funded healthcare education.
PMID- 17042361
TI - Pay: mixed blessings for HCAs.
PMID- 17042362
TI - Will you still need me?
PMID- 17042363
TI - 'Finest of the fine arts'.
AB - Florence Nightingale said nursing is 'the finest of the fine arts'. In the last
of our Heart of Nursing series, we consider the similarities between nursing care
and art.
PMID- 17042365
TI - 'I turned my life around'.
PMID- 17042364
TI - Mission to explain.
AB - Lack of information adds to the fear of cancer for people from black and minority
ethnic groups. Rose Thompson is making a difference.
PMID- 17042366
TI - HIV carriers must be honest with prospective partners.
PMID- 17042367
TI - Assessment of a patient with an acute exacerbation of asthma.
AB - This article is a reflective account of the respiratory assessment of a patient
experiencing an acute exacerbation of asthma in hospital. The patient's signs and
symptoms are examined and an analysis of the respiratory assessment and the
patient's treatment is provided.
PMID- 17042368
TI - Cross-cultural information leaflets.
AB - This article reflects on the development of leaflets in Urdu to support families
in weaning children from milk to solids. Limitations in the translation process
are highlighted and the importance of determining clients' needs is emphasised.
PMID- 17042369
TI - Specialist palliative care for patients with non-cancer diagnosis.
AB - All patients with palliative care needs should receive an equitable service, and
there is evidence to suggest that patients with life-limiting illnesses other
than cancer would benefit from specialist palliative care services. The author
discusses how this might be achieved and the barriers that exist to prevent it
happening.
PMID- 17042370
TI - Assessment of learning in clinical practice.
AB - This article explores assessment in clinical practice, including the measures
that can be taken to ensure that it is conducted fairly and the appropriateness
of the methods undertaken.
PMID- 17042371
TI - Acute coronary care.
PMID- 17042372
TI - A hard day's night.
PMID- 17042374
TI - Free and easy.
PMID- 17042373
TI - All together now.
PMID- 17042375
TI - Identification of lipopolysaccharide-binding proteins in porcine milk.
AB - Septicemia and endotoxemia initiated by bacterial lipopolysaccharide (LPS) are
relatively common in suckling and weaned piglets. Maternal milk is a source of
both nutrition and immune protection for piglets. Passive transfer of colostral
antibodies is necessary for protection of neonatal piglets against diseases, but
the concentration of immunoglobulins in milk rapidly declines during the 1st wk
of lactation in all mammals. We hypothesized, therefore, that nonimmunoglobulin
substances in milk contribute to the innate protection of neonates against
septicemia during the suckling period. Using LPS-affinity chromatography for
isolation of LPS-binding proteins and liquid chromatography-mass spectrometry for
their identification, we identified in porcine milk the following proteins with
LPS-binding capacity: lactoferrin, soluble CD14, serum amyloid A, alpha-S1
casein, beta-casein, and kappa-casein. For lactoferrin, alpha-S1 casein, and
kappa-casein, in vitro pepsin digestion did not inhibit LPS-binding activity,
whereas combined digestion with pepsin and pancreatin abolished it. The biologic
functions of these LPS-binding proteins and peptides were not determined.
PMID- 17042376
TI - Influence of lidocaine and diazepam on peri-induction intraocular pressures in
dogs anesthetized with propofol-atracurium.
AB - The purpose of this study was to evaluate the effects on the intraocular pressure
(IOP) of lidocaine or diazepam administered intravenously (IV) before induction
of anesthesia with propofol-atracurium and orotracheal intubation in normal dogs,
as well as the effects on the IOP of lidocaine applied topically to the larynx
after induction with propofol-atracurium. We randomly assigned 32 random-source
dogs, obtained from municipal pounds, to receive the following: lidocaine, 2
mg/kg IV, with saline, 0.1 mL/kg topically applied to the larynx (LIDOsal);
saline, 0.1 mL/kg IV, with lidocaine, 2 mg/kg topically applied to the larynx
(SALlido); diazepam (Valium), 0.25 mg/kg IV, with saline, 0.1 mL/kg topically
applied to the larynx (VALsal); or saline, 0.1 mL/kg IV, with saline, 0.1 mL/kg
topically applied to the larynx (SALsal). We measured arterial pressure directly,
by means of an indwelling catheter placed in a peripheral artery. Anesthesia was
induced with propofol, 8 mg/kg IV, until loss of jaw tone, followed by
atracurium, 0.3 mg/kg IV. We measured the IOP in triplicate in each eye before
premedication, before induction, before intubation, and after intubation. After
induction, the IOP was significantly increased except in the VALsal group, in
which the IOP was significantly lower than in the negative-control group before
intubation. After intubation, the IOP was significantly elevated in all the
groups compared with the values before induction. Cardiovascular parameters were
essentially similar in all the groups, except for a significant increase in blood
pressure after intubation in the SALlido group. Thus, propofol-atracurium
anesthesia causes an increase in IOP that is blunted by diazepam. However,
diazepam does not blunt the increase in IOP observed with intubation.
PMID- 17042377
TI - Postoperative effects of anesthesia and surgery on resting energy expenditure in
horses as measured by indirect calorimetry.
AB - In this study, we aimed to define the effects of anesthesia and surgery on the
resting energy expenditure of horses in experimental conditions. Six horses were
used in a longitudinal study with 2 study periods: before and after anesthesia
and surgery. Every horse underwent a standard 90-min ventral midline exploratory
laparotomy. Oxygen uptake (VO2) and carbon dioxide output (VCO2) were measured,
with the use of a closed-circuit spirometry system, on 5 consecutive days
immediately before and after the surgery. In 3 consecutive 5-min periods each
day, the expired air was collected in a Collins spirometer. Samples of the
expired gas were drawn from the spirometer through a drying column into O2 and
CO2 analyzers. Resting energy expenditure was calculated as [(VO2 STPD*3.94) +
(VCO2 STPD*1.11)]*1.44. This study showed that anesthesia and ventral midline
exploratory laparotomy in experimental conditions increase the postoperative
caloric demand in horses by an average of 1.0 Mcal/d, which represents
approximately a 10% increase (P = 0.03). Additional studies in critically ill
horses after surgery are needed to determine their caloric needs and to optimize
their nutritional management.
PMID- 17042378
TI - Serodiagnostic comparison of enzyme-linked immunosorbent assay and surface
plasmon resonance for the detection of antibody to porcine circovirus type 2.
AB - This paper describes the cloning and expression of the capsid protein of Porcine
circovirus type 2 (PCV2) in an Escherichia coli expression system that was used
to produce a fusion protein for subsequent immunologic studies: enzyme-linked
immunosorbent assay (ELISA) and surface plasmon resonance (SPR). Polymerase chain
reaction was used to amplify the gene encoding the capsid protein from the DNA of
PCV2. The protein was then cloned into a pRSET prokaryotic expression vector.
Western blot analysis revealed that the recombinant protein gave strong signals
on a polyvinylidene difluoride membrane when exposed to the serum from a pig
infected with PCV2. The expressed protein was purified and used as an antigen for
the ELISA and SPR study. A protein chip based on SPR was developed, and the
diagnostic potential of SPR was compared with that of ELISA with the use of 70
serum samples obtained from 6 pig farms. There was a strong positive correlation
between the ELISA and SPR titers (r = 0.877, P < 0.01). Therefore, this
recombinant capsid protein can be used as an antigen for serologic studies, and
the SPR, a label-free method, appears to be a valuable and reproducible tool in
the serodiagnosis of a PCV2 infection.
PMID- 17042379
TI - The role of immunostimulation in the development of postweaning multisystemic
wasting syndrome in pigs under field conditions.
AB - We evaluated the effects of immunostimulation in the development of postweaning
multisystemic wasting syndrome (PMWS) in 930 pigs 53 to 54 d old in a
grower/finisher barn with a history of PMWS. The pigs were allocated to 5
treatment groups: 4 groups received a single intramuscular injection of RespiSure
ONE (a commercial Mycoplasma hyopneumoniae vaccine; n = 197), Emulsigen (an oil
based adjuvant; n = 172), Alhydrogel (an aluminum-hydroxide-based adjuvant; n =
172), or physiologic saline (n = 218); 1 group received no treatment (n = 171).
Pigs affected by PMWS were found in all the groups. Antigen to Porcine circovirus
type 2 (PCV-2) was detected by immunohistochemical testing within lesions of
mesenteric lymph node, spleen, Peyer's patch, and lung of affected pigs. There
was no significant difference in the incidence of PMWS among the groups. The
findings indicate that immunostimulation did not influence the expression of PMWS
in this study. Thus, routine vaccination against swine diseases may not
significantly contribute to the occurrence of PMWS under field conditions.
PMID- 17042380
TI - In vitro heterogeneity of osteogenic cell populations at various equine skeletal
sites.
AB - Bone cell cultures were evaluated to determine if osteogenic cell populations at
different skeletal sites in the horse are heterogeneous. Osteogenic cells were
isolated from cortical and cancellous bone in vitro by an explant culture method.
Subcultured cells were induced to differentiate into bone-forming osteoblasts.
The osteoblast phenotype was confirmed by immunohistochemical testing for
osteocalcin and substantiated by positive staining of cells for alkaline
phosphatase and the matrix materials collagen and glycosaminoglycans. Bone
nodules were stained by the von Kossa method and counted. The numbers of nodules
produced from osteogenic cells harvested from different skeletal sites were
compared with the use of a mixed linear model. On average, cortical bone sites
yielded significantly greater numbers of nodules than did cancellous bone sites.
Between cortical bone sites, there was no significant difference in nodule
numbers. Among cancellous sites, the radial cancellous bone yielded significantly
more nodules than did the tibial cancellous bone. Among appendicular skeletal
sites, tibial metaphyseal bone yielded significantly fewer nodules than did all
other long bone sites. This study detected evidence of heterogeneity of equine
osteogenic cell populations at various skeletal sites. Further characterization
of the dissimilarities is warranted to determine the potential role heterogeneity
plays in differential rates of fracture healing between skeletal sites.
PMID- 17042381
TI - Cervical and coelomic radiologic features of the loggerhead sea turtle, Caretta
caretta.
AB - Many investigators have undertaken radiologic studies in chelonians. However,
descriptive papers focusing on the radiographic anatomy are limited to only a few
species. The purpose of this article is to provide the normal cervical and
coelomic radiographic appearance of the loggerhead sea turtle (Caretta caretta),
in the dorsoventral view, and to indicate useful landmarks to identify internal
anatomic structures. Dorsoventral radiographs were taken of the neck and body of
30 loggerhead sea turtles by means of analog and digital radiography. At various
points, distortion or superimposition of images due to the natural curvature of
the shell hindered the accuracy of interpretation. The pectoral and pelvic
girdles were easily recognized. Important external landmarks included the
vertebral and lateral scutes, and important internal landmarks included the
bronchi, coracoid bones, the caudal border of the pulmonary fields, and the
acetabulum.
PMID- 17042382
TI - Myeloperoxidase concentration in bronchoalveolar lavage fluid from healthy horses
and those with recurrent airway obstruction.
AB - The aim of this work was to measure the myeloperoxidase (MPO) concentration in
bronchoalveolar lavage (BAL) fluid collected from horses with recurrent airway
obstruction (RAO), both in crisis and in remission, as well as from healthy
horses. Seven horses with RAO were exposed to moldy hay until the maximum change
in pleural pressure was greater than 1.5 kPa. At that point, BAL was performed,
and the total cell counts and percentages in the fluid were immediately
determined. To measure the MPO concentration in BAL-fluid supernatant, we used a
specific enzyme-linked immunosorbent assay with polyclonal antibodies against
equine MPO. The tests were repeated on the horses with RAO after they had spent 2
mo on pasture. Six healthy horses serving as controls underwent the same tests.
The absolute and relative neutrophil counts and the MPO concentration in the BAL
fluid were significantly greater in the horses with an RAO crisis than in the
control horses. After 2 mo on pasture, the horses that had been in RAO crisis
were clinically normal, and their neutrophil counts and MPO levels in BAL fluid
had significantly decreased; during remission their neutrophil counts were not
significantly different from those in the healthy horses, but their MPO
concentration remained significantly higher. This study showed that determining
the MPO concentration in a horse's BAL fluid is technically possible and that
during remission from RAO the concentration remains higher than normal. Thus, MPO
may be a marker of neutrophil presence and activation in the lower airways.
PMID- 17042383
TI - The impact of animal age, bacterial coinfection, and isolate pathogenicity on the
shedding of porcine reproductive and respiratory syndrome virus in aerosols from
experimentally infected pigs.
AB - The objective of this study was to evaluate the role of different variables
(animal age, bacterial coinfection, and isolate pathogenicity) on the shedding of
Porcine reproductive and respiratory syndrome virus (PRRSV) in aerosols. Animals
were grouped according to age (2 versus 6 mo) and inoculated with a PRRSV isolate
of either low (MN-30100) or high (MN-184) pathogenicity. Selected animals in each
group were also inoculated with Mycoplasma hyopneumoniae. The pigs were
anesthetized and aerosol samples (1000 breaths/sample) collected on alternating
days from 1 to 21 after PRRSV inoculation. The results indicated that animal age
(P = 0.09), M. hyopneumoniae coinfection (P = 0.09), and PRRSV isolate
pathogenicity (P = 0.15) did not significantly influence the concentration of
PRRSV in aerosols. However, inoculation with the PRRSV MN-184 isolate
significantly increased the probability of aerosol shedding (P = 0.00005; odds
ratio = 3.22). Therefore, the shedding of PRRSV in aerosols may be isolate
dependent.
PMID- 17042384
TI - Prevalence of Brucella abortus antibodies in equines of a tropical region of
Mexico.
AB - A cross-sectional study was conducted to determinate the seroprevalence rate of
equine brucellosis in the state of Tamaulipas, Mexico. Serum samples from 420
equines were analyzed with the Rose Bengal test at cell concentrations of 3% (RBT
3%) and 8% (RBT-8%), and positive results were confirmed with the Rivanol test
(RT). Risk factors were determined with the prevalence ratio (PR) and the use of
variables generated from a questionnaire administered to the animals' owners.
Serum from 1 stallion had positive results with both the RBT-8% and the RT, for a
seroprevalence rate of 0.238%. Drinking of water from a pond that was also used
by cattle and dogs was the only associated risk factor for this animal (PR =
0.25). However, the results were considered false-positive, because the results
for other horses in the same environmental conditions were negative. Although
brucellosis is considered endemic in ruminants in the study area, the results
obtained suggest that equines are not a reservoir of brucellosis and do not play
an important role in the epidemiologic patterns of this disease in northeastern
Mexico.
PMID- 17042385
TI - Plasma concentration of vitamin C in dogs with a portosystemic shunt.
AB - Most mammals, including dogs, synthesize vitamin C in the liver. We measured the
plasma concentration of vitamin C to assess the body vitamin C status in 15 dogs
with a portosystemic shunt (PSS). The plasma biochemical parameters indicated
liver abnormalities in all the dogs. In contrast, the plasma concentration of
vitamin C ranged from 2.21 to 9.03 mg/L in the 15 dogs and was below the
reference range (3.2 to 8.9 mg/L) in only 2 dogs. These findings suggest that
vitamin C status is not impaired in dogs with PSS.
PMID- 17042386
TI - Cardiorespiratory effects of desflurane in dogs given romifidine or medetomidine
before induction of anesthesia with propofol.
AB - The objective of this study was to evaluate the use of desflurane after induction
of anesthesia with propofol in dogs sedated with romifidine or medetomidine. Each
of 8 healthy dogs received intravenously, in random order, 3 preanesthetic
protocols: romifidine, 40 microg/kg of body weight (BW) (R40); romifidine, 80
microg/kg BW (R80); and medetomidine, 10 microg/kg BW (MED). Cardiovascular and
respiratory variables were recorded during the procedure. Time to extubation,
time to sternal recumbency, and time to standing were also recorded. Heart rate
and respiratory rate decreased significantly during sedation from baseline
values, but there were no differences between the means for the 3 preanesthetic
protocols. Mean values for heart rate, mean arterial blood pressure, systolic
arterial pressure, diastolic arterial pressure, respiratory rate, tidal volume,
arterial oxygen saturation, end-tidal CO2 level, pH, and arterial blood gas
values during anesthesia were similar for the 3 protocols. The mean end-tidal
desflurane concentration was significantly lower with the R80 protocol than with
the R40 protocol. The mean time to extubation was significantly shorter with the
R40 protocol than with the R80 and MED protocols.
PMID- 17042387
TI - Serum and urine concentrations of trypsinogen-activation peptide as markers for
acute pancreatitis in cats.
AB - The purpose of this study was to compare the clinical utility of the serum
concentration of feline trypsin-like immunoreactivity (fTLI), the plasma and
urine concentrations of trypsinogen-activation peptide (TAP), and the ratio of
the urine TAP and creatinine concentrations (TAP:Cr) in the diagnosis of feline
acute pancreatitis. We used 13 healthy cats and 10 cats with a diagnosis of acute
pancreatitis. The mean serum fTLI and plasma TAP concentrations were
significantly higher in the cats with acute pancreatitis than in the healthy cats
(P < 0.05); the mean urine TAP concentrations and the median urine TAP:Cr ratios
were not significantly different. Among the cats examined in this study, there
was no benefit of plasma TAP over serum fTLI in the evaluation of suspected acute
pancreatitis.
PMID- 17042388
TI - The effects of equine skin preparation on transdermal drug penetration in vitro.
AB - An increasing number of formulations are applied to equine skin, yet variable
penetration can affect efficacy, or the incidence of adverse effects, or both. To
investigate the effects of common methods of skin preparation on transdermal drug
penetration in vitro, we clipped, harvested, and froze skin samples from 5
Thoroughbred geldings. Thawed samples were prepared as follows: control (no
preparation); cleaned with aqueous chlorhexidine (Aq-C, 0.1% w/v); cleaned with
alcoholic chlorhexidine (Al-C, 0.5% w/v); shaved (Sh); or tape-stripped (Ta) with
the use of adhesive tape. The samples were then placed in diffusion cells, and 2
g of methylsalicylate (MeSa) gel (Dencorub) was applied to the stratum corneum
side. The penetration of MeSa and its analyte, salicylate (Sa), through the skin
samples was measured over 10 h. Compared with control skin, significantly more
MeSa penetrated through skin prepared with Al-C or Sh (P < 0.01) or with Aq-C or
Ta (P < 0.05), and significantly more Sa was recovered in the receptor phase from
skin prepared with Aq-C, Al-C, or Sh (P < 0.05) or with Ta (P < 0.01). A
significantly higher rate of penetration and shorter lag time were also noted for
MeSa with all the prepared skin samples, compared with the control samples. The
results show that clinical techniques routinely used to clean or prepare skin can
significantly affect the rate and extent of penetration of a topically applied
drug. This may result in greater systemic availability of active drug, which
could lead to enhanced efficacy and, possibly, a higher incidence of adverse
effects.
PMID- 17042389
TI - Occurrence of esophageal and gastric cancer in Alaska Natives, 1969-2003.
AB - BACKGROUND: Early reports of esophageal and gastric cancer in American
Indians/Alaska Natives documented high rates. METHODS: Esophageal and gastric
cancers in Alaska Natives were reviewed for 1969-2003 using the Alaska Native
Tumor Registry database. Alaska Native incidence rates were age-adjusted and
compared to rates of several US populations. RESULTS: The incidence of esophageal
and gastric cancer has remained relatively stable during the 35-year period.
Gastric cancer is higher than that seen in US Whites, Blacks and American Indians
of New Mexico and similar US Asian/Pacific Islanders. Esophageal cancer incidence
is higher than US Whites, Asian/Pacific Islanders and American Indians of New
Mexico but similar to US Blacks. CONCLUSION: The rates of esophageal and gastric
cancer in the Alaska Native population have remained high over 35 years. While
the rate of gastric cancer has declined among US Whites, a similar decline has
not been seen in Alaska Natives.
PMID- 17042390
TI - WWAMI--Alaska's Medical School.
AB - In 2005 Alaska's medical school is WWAMI, but the WWAMI program today is far
different than it was in 1971 when it began with 5 Alaskans in a class of 9 at
Fairbanks. WWAMI students may now complete nearly 3 years of the 4-year program
in state. They can now complete postgraduate residency training at the Alaska
Family Medicine Residency in Anchorage. Alaska also benefits from a host of other
WWAMI initiatives, such as the MedCon medical consultation service. On the other
hand, the Alaska WWAMI program still allows for only 10 medical school positions,
as it has since its inception. In the face of a worsening physician shortage in
the state, class expansion appears to be warranted. When comparing this option
versus the costs of recruitment or the possibilities of increasing graduate
medical education in the state, class size increase is well justified.
PMID- 17042391
TI - The little boy from Bettles.
PMID- 17042393
TI - Fifty? Prepare for the battle for your life.
PMID- 17042392
TI - Generational approaches to current nursing issues. How younger and older nurses
can coexist.
PMID- 17042394
TI - Online lactation education tutorial.
PMID- 17042396
TI - Changes in Alabama's Child Restraint law.
PMID- 17042395
TI - Campaign for fragrance free health care in the U.S.
PMID- 17042397
TI - Breastfeeding can reduce infant infections and health care costs.
PMID- 17042398
TI - Accommodating the needs of the aging registered nurse workforce.
AB - The average age of registered nurses is 45, according to the 2000 national Sample
Survey of Registered Nurses as shown in results released in February 2002. With
the nursing workforce aging and few young people entering the profession
administrators will need to entertain ideas that will aid in retention of the
older nurses. A descriptive survey design was used to determine the awareness of
and any plans for the aging Registered Nurse (RN) workforce by Alabama nursing
administrators in hospitals and nursing homes. The average of all responding
facilities for employed RNs over the age of 55 is 11.78%, with hospitals average
being 11.68% and nursing homes being 11.43%. Fifty-four percent of administrators
were at least moderately aware of the aging workforce. There was a higher
percentage noted in nursing homes (57%) than hospitals (40%). All administrators
responded that they wished to retain older RNs. Unfortunately, 96.3% of Alabama
hospitals and nursing homes have no policies currently in place to address the
needs of the aging registered nurse workforce.
PMID- 17042399
TI - Dementia: thief of hearts.
PMID- 17042400
TI - Exploring the relation of independent and interdependent self-construals to why
and how people pursue personal goals.
AB - The authors examined whether independent or interdependent self-construals were
associated with the way in which individuals pursued personal goals. Individuals
with an independent self-construal orient toward personal-goal pursuit, whereas
individuals with interdependent self-construal prioritize in-group goals above
personal ones. The authors used a 1-week, prospective goal-setting paradigm. The
present results revealed that interdependent self-construals were significantly
associated with introjected reasons for pursuing goals, experiencing conflict
among goals, and achieving less goal progress. Independent self-construals were
significantly associated with intrinsic and identified reasons for goal pursuit
and greater goal progress. There was some evidence that the relation of
interdependent and independent self-construals to goal progress was mediated by
goal conflict and goal intrinsic motivation, respectively. The present results
also replicated previous research indicating the goal-setting benefits of
intrinsic motivation, implementation intentions, and goal harmony.
PMID- 17042401
TI - The influence of group diversity on intergroup bias following recategorization.
AB - Although recategorization in laboratory studies of nominal groups has received
considerable support, some researchers have criticized such efforts as impossible
when demographic diversity is the source of group identification. Therefore, the
purpose of the present study was to examine the influence of diversity on
intergroup bias among groups where recategorization efforts had occurred. The
author gathered data from 162 undergraduate students (as either 54 3-participant
groups or 27 6-participant groups; 107 men and 55 women). Results of moderated
regression analysis indicated that, although diversity did not influence
participants' perceptions of the aggregate as a single group, diversity did
influence intergroup bias. Specifically, bias was highest when more homogeneous
groups merged with more diverse groups. The author discussed results in terms of
theoretical contributions and implications for managing diversity.
PMID- 17042402
TI - Correlates of minimal dating.
AB - Researchers have associated minimal dating with numerous factors. The present
author tested shyness, introversion, physical attractiveness, performance
evaluation, anxiety, social skill, social self-esteem, and loneliness to
determine the nature of their relationships with 2 measures of self-reported
minimal dating in a sample of 175 college students. For women, shyness,
introversion, physical attractiveness, self-rated anxiety, social self-esteem,
and loneliness correlated with 1 or both measures of minimal dating. For men,
physical attractiveness, observer-rated social skill, social self-esteem, and
loneliness correlated with 1 or both measures of minimal dating. The patterns of
relationships were not identical for the 2 indicators of minimal dating,
indicating the possibility that minimal dating is not a single construct as
researchers previously believed. The present author discussed implications and
suggestions for future researchers.
PMID- 17042403
TI - Relationship styles of self-focused autonomy, other-focused connection, and
mutuality among Mexican American and European American college students.
AB - The author examined relationship styles of self-focused autonomy (SFA), other
focused connection (OFC), and mutuality among 415 European and Mexican American
young adults in 2 U.S. colleges. Mutuality was the most commonly reported style
for both ethnic groups, although Mexican American men were more likely than the
others to indicate that they had the SFA style. Mexican American participants
perceived their fathers' styles as SFA more often than did the others regarding
either of their parents' styles. Mutuality was associated with the best mental
health outcomes regardless of gender or ethnicity. The present results indicate
that the cultural influences on autonomy and connection are complex and that
collectivistic cultural contexts may sometimes promote autonomy concerns in men.
PMID- 17042404
TI - Rethinking culture and self-construal: China as a middle land.
AB - Amid criticisms of current paper-and-pencil type questionnaires measuring self
construal across cultural groups, the authors used a graphic representation scale
to examine whether Anglo Canadians (N = 220) were more independent than Mainland
Chinese (N = 196) and Indians (N = 212) in construing their relationships with
closest family member, family members, closest friend, friends, (other)
relatives, colleagues, and neighbors. Data generated 5 intriguing findings: (a)
Chinese were more interdependent than Canadians but less so than Indians,
indicating that Chinese culture has become more individualistic. (b) Canadians
were more independent than Chinese in 6 relationship dimensions but were as
interdependent as Chinese in self-closest-friend connectedness, somewhat
contradicting 1 assumption of theories of independent-interdependent self
construal and individualism-collectivism (I-C). (c) Canadians were more
independent than Indians in all relationship dimensions, supporting theories of
independent-interdependent self-construal and I-C. (d) Chinese were as
interdependent as Indians in self-closest-family-member, self-close-family
members, and self-relatives connectedness but more independent than Indians in
the other categories of self-other relationships. (e) Participants' age did not
have strong correlations with variables measuring self-construal in any sample,
indicating that a person's attachment style may not change greatly over a
lifespan. The authors discussed theoretical and methodological implications.
PMID- 17042405
TI - Queer in Southern MSW programs: lesbian and bisexual women discuss stigma
management.
AB - The author described the processes by which a sample of lesbian and bisexual
women assessed and managed prejudice and discrimination while pursuing degrees of
masters of social work. The author presented as being pivotal to the
participants' assessments of social work settings the social cues that
participants identified as indicative of potential attitudes and beliefs
regarding lesbian and bisexual women. In addition, the author discussed
strategies that the women used to manage others' expression of prejudicial
attitudes. Through these interactional processes, the participants demonstrated
that they were active in shaping and reducing their experience of oppression.
PMID- 17042406
TI - Procrastination and demographic characteristics in Spanish adults: further
evidence.
PMID- 17042407
TI - Benevolent sexism and cosmetic use: a replication with three college samples and
one adult sample.
PMID- 17042408
TI - Wisconsin's health disparities challenge physicians.
PMID- 17042409
TI - Further need for EC awareness and access.
PMID- 17042410
TI - Clinical use of evidence-based medicine--clinical questions: Acetylcysteine, a
new treatment for an old foe?
AB - This is a small, good quality, randomized controlled trial that shows a modest
slowing in the deterioration of VC and DLco with the addition of high dose N
acetylcysteine to standard therapy in IPF. Overall the study should be
interpreted with caution given its high drop out rate, which may have biased the
results towards a more dramatic slowing of the disease progression. There were no
differences in dyspnea score or functional status. There was no increase in the
adverse events in the N-acetylcysteine group and the medication is inexpensive.
Given only modest effects of N-acetylcysteine on VC and DLco, no change in
functional scores, and the flaws of the study we would hesitate to use N
acetylcysteine as standard therapy in all patients with IPF.
PMID- 17042411
TI - Wisconsin Medical Society embarks on campaign to define high-quality care.
PMID- 17042412
TI - Proposed constitutional amendment means restrictions of health care access.
AB - It is difficult to read all of the current studies about sexual orientation and
not hypothesize that some combination of genetic and developmental factors must
be involved. It seems likely that homosexuality is a trait like left handedness.
Treating our gay, lesbian, bisexual, or transgender patients any differently than
we treat our left handed patients makes no sense. And voting for the proposed
constitutional amendment that would deny them access to health care doesn't make
sense either.
PMID- 17042413
TI - An evidence-based context to address health care for gay and lesbian patients.
AB - There is extensive, credible evidence in the medical literature, and overwhelming
consensus among professional medical organizations, that disparities in health
care provided to gay and lesbian patients and their families must be addressed
and changed. As physicians, we continue to assess the latest medical evidence in
order to provide the highest quality health care to all our patients. We will
tell the truth when attempts to discriminate, whether legislative or societal,
harm our patients or hamper our ability to care for them. Examples from Michigan,
Ohio, and Nebraska, where constitutional amendments banning same sex civil unions
or marriage have passed, are noteworthy, with increasing legal challenges to
domestic partnerships. These discriminatory laws and amendments have jeopardized
health care decision-making, hospital visitation rights, health insurance, and
legal protections for gay as well as heterosexual couples. In Wisconsin, we can
and must do better than that as we strive to improve the health of all of our
citizens.
PMID- 17042414
TI - Medication costs in Wisconsin Medicaid: Waste not, want not?
PMID- 17042415
TI - CA-MRSA triangulation: virulent strains, susceptible hosts, and contaminated
environments.
PMID- 17042416
TI - Monitoring racial/ethnic mortality disparities in Wisconsin: 1991-2000.
AB - BACKGROUND: Wisconsin has a goal to eliminate health disparities by 2010, but
there is no consistent standard used to evaluate progress. Methodological debates
persist regarding using individual group change or relative comparisons to
monitor disparities. OBJECTIVES: To examine mortality disparities among
racial/ethnic populations in Wisconsin using statistically significant changes in
individual population mortality rates and rate ratios as measures of disparity.
These measures are proposed to monitor and evaluate progress in eliminating
racial/ethnic health disparities. METHODS: The Wisconsin Interactive Statistics
on Health database was queried to obtain Wisconsin all-cause mortality data by
race and age for the 1991-1995 and 1996-2000 periods. Age-specific and age
adjusted rates were compared across 5 major racial/ethnic populations in
Wisconsin. RESULTS: Age-adjusted mortality generally declined for all
racial/ethnic populations in Wisconsin from 19911995 to 1996-2000. However,
disparities increased significantly for African American infants, African
Americans 45-64 years old, and Hispanics/Latinos 25-44 years old. Using non
Hispanic whites as a referent resulted in a paradoxical increase in disparities
for Hispanics/Latinos despite a significant reduction in mortality in this group.
CONCLUSION: A statistically significant percent change in mortality rates and
rate ratios is a useful standard to monitor health disparities and foster
communication and targeted action around Wisconsin's goal to eliminate
racial/ethnic health disparities.
PMID- 17042417
TI - Disparities in oral and pharyngeal cancer incidence and mortality among Wisconsin
residents, 1999-2002.
AB - OBJECTIVE: Compare incidence, mortality, and trends of oral cancer (including the
pharynx) in Wisconsin and the United States by race and gender from 1999-2002.
METHODS: Age-adjusted incidence rates were compared using data from the Centers
for Disease Control and Prevention (CDC WONDER). Mortality rates were compared
using data from the Wisconsin Interactive Statistics on Health (WISH) and CDC US
Cancer Statistics. RESULTS: Incidence rates for oral cancer were higher among
males than females in both Wisconsin and the United States. Trends in the
incidence rate show the gender disparity has not changed. Furthermore, the
incidence rate for African American males is higher in Wisconsin than in the
United States. Mortality rates for males were approximately 2 times higher than
females in Wisconsin and the United States. Additionally, African American males
are more likely than white males to die from this form of cancer, and the
likelihood is higher in Wisconsin than in the United States (2.4 versus 1.8,
respectively). CONCLUSION: Racial disparities in oral cancer for African American
males are greater in Wisconsin than in the United States. This may result from
variation in access to oral health care, tobacco and alcohol use, as well as
limited resources in detection and prevention methods. Wisconsin should focus its
oral cancer prevention activities on this high-risk group.
PMID- 17042418
TI - Analysis of anti-epileptic drugs in fee-for-service Wisconsin Medicaid.
AB - INTRODUCTION: Off-label use of prescription drugs presents issues of patient
safety and can significantly increase the overall prescription drug expenditure
in providing health care services. As a class, the anti-epileptic drugs are
provided for off-label use on a frequent basis. Because of the safety issues and
increased cost with such prescribing practices, the Wisconsin Medicaid Drug
Utilization Review Board (DUR board) reviewed the use of anti-epileptic agents in
the fee-for-service Wisconsin Medicaid population. METHODS: Prescribers with the
highest amount paid for drugs in this class, and for which there was no
appropriate diagnosis (intervention group), were provided with a list of the
patients for whom they prescribed the drug for an off-label clinical condition. A
total of 488 prescribers were contacted and informed of the costs and hazards of
off-label prescribing. RESULTS: Using a comparison group of patients who were
prescribed anti-epileptic agents but who did not reach the amount paid threshold
(non-intervention group), the study demonstrated a decrease of 6652 prescriptions
in the intervention group and an increase of 4194 in the non-intervention group.
In addition, expenditures for the intervention group dropped by dollar 752,232
and the non-intervention group rose by dollar 835,351. It is estimated that the
overall financial impact of this intervention was a savings of dollar 2,552,077
over the 5-month period of review.
PMID- 17042419
TI - Community acquired methicillin resistant Staphylococcus aureus: A Wisconsin
perspective.
AB - Community-acquired methicillin-resistant Staphylococcus aureus have swept across
the United States, causing severe morbidity and mortality (see Table 1). This
manuscript provides some illustrative cases seen in Wisconsin.
PMID- 17042420
TI - Injuries from ultimate frisbee.
AB - OBJECTIVE: This paper will explore ultimate frisbee injuries. METHOD: This study
uses an anonymous, retrospective, self-reported survey of 135 adult athletes at a
Midwestern ultimate frisbee tournament. Subjects were queried regarding injuries
to specific body parts, those causing missed activity, recurring injuries,
medical care sought, basic demographic data, duration of participation,
handedness, and eye color. Categorical data were analyzed by chi-square tests.
Qualitative responses were categorized by themes. RESULTS: Respondents had a mean
age of 28 years and 59% were male. Mean playing time was 8.2 hours per week and
7.5 total years. Ultimate frisbee injuries included muscle strains (76% of
subjects), ankle (65%), knee (53%), shoulder (37%), head (30%), and rib (21%)
injuries. Blisters/calluses and black toenails were frequently mentioned.
Recurrent injuries were reported in 49%. Shoulder injuries were more common in
men than women (47% versus 24%, P<0.02). Of respondents, 88% have missed ultimate
frisbee activity due to injury, and 71% have sought medical care for ultimate
frisbee injuries. CONCLUSIONS: The majority of surveyed ultimate frisbee players
experience injuries and seek medical care. Health care professionals should be
aware of the injuries associated with ultimate frisbee and further studies should
focus on prevention and education strategies.
PMID- 17042421
TI - Is the ankle-brachial index a useful screening test for subclinical
atherosclerosis in asymptomatic, middle-aged adults?
AB - BACKGROUND: Measurement of the ankle-brachial index (ABI) is recommended as a
screening test for cardiovascular risk prediction in individuals > or = 50 years
old; however, there is little data regarding the utility of the ABI as a
screening test in individuals for whom physicians actually order non-invasive
testing for cardiovascular risk prediction. METHODS: This study included 493
consecutive asymptomatic patients without known atherosclerotic vascular disease
who were referred by their physician for measurement of the ABI and ultrasound
measurement of carotid intima-media thickness (CIMT). ABI values were classified
as "reduced" (<0.9), "normal" (0.9-1.3), and "increased" (>1.3). RESULTS: The
mean age of the patients was 55.3 (standard deviation 7.5) years. Only 1 patient
had a reduced ABI (0.2%). ABI values tended to be higher in those with increased
CIMT (P=0.051); however, CIMT was not significantly different between those with
normal and increased ABI values (P=0.802). There were no significant differences
in the prevalence of traditional cardiovascular risk factors or carotid plaque
presence among the ABI groups. CONCLUSIONS: Despite recommendations, the ABI is
not sensitive as a screening tool for detecting subclinical atherosclerosis in
asymptomatic middle-aged individuals.
PMID- 17042422
TI - Northern Wisconsin married couple infected with blastomycosis.
AB - Blastomycosis is an uncommon, chronic, granulomatous disease caused by the
dimorphic fungus Blastomycosis dermatitidis. The great majority of infections
start with primary pulmonary involvement through inhalation of spores.
Hematogenous dissemination to other sites occurs in 25% to 30% of cases. The most
common secondary site is the skin, followed in order by bone, genitourinary
system, and central venous system. We report 2 cases of blastomycosis originating
in a husband and wife who were both symptomatic and diagnosed with blastomycosis
within 4 months of each other. One presented with pulmonary symptoms, the other
with cutaneous symptoms. These 2 cases of husband and wife are of interest not
only because of their rarity but also because of the potential mode of
transmission.
PMID- 17042423
TI - Advancing the Wisconsin idea.
PMID- 17042424
TI - Want to retire early? How to avoid the 10% penalty.
PMID- 17042425
TI - MetaStar's health care and culture project: does your clinic meet federal
standards?
PMID- 17042426
TI - [The question of Gretchen in Faust..A quality the qualified nurse has to
anticipate].
PMID- 17042427
TI - [We gain nothing from blocking].
PMID- 17042428
TI - [Integration of quality health nursing into a clear concept].
PMID- 17042429
TI - [The reason for recognizing the patient's needs].
PMID- 17042430
TI - [Different "management" in old age].
PMID- 17042431
TI - [Regional networking].
PMID- 17042432
TI - [Indications for a new tariff system].
PMID- 17042433
TI - [When help becomes a crime].
PMID- 17042434
TI - [Fundamentals in our calling].
PMID- 17042435
TI - [Great demands with deadly outcomes].
PMID- 17042436
TI - ["I have had the possibility of experimenting with collaboration."].
PMID- 17042437
TI - [No tiny nurse, nor any superior nursing help].
PMID- 17042438
TI - [A "non-suicide contract" under the guise of prevention].
PMID- 17042439
TI - [Health education and professional promotion].
PMID- 17042440
TI - [Many words and few deeds].
PMID- 17042441
TI - ["I am fascinated by the wealth of the continuity of nursing"].
PMID- 17042442
TI - A sedation dental practice.
PMID- 17042443
TI - Dental anesthesiology--an access to care issue.
PMID- 17042444
TI - Current sedation practice in Israel.
PMID- 17042445
TI - Dentist anesthesiologists.
PMID- 17042446
TI - Sedation and safety: 36 years of perspective.
PMID- 17042447
TI - Use of midazolam to modify children's behavior in the dental setting.
PMID- 17042448
TI - Effective and safe pediatric oral conscious sedation: philosophy and practical
considerations.
AB - Because dental treatment can represent a threatening event for some children,
need exists to include sedation within our management arsenal. By definition, pre
cooperative children and those lacking in cooperative ability have immature
cognitive skills, a highly restricted range of coping abilities, brief or
negligible attention spans, and virtually no experience coping with stress. As
result, they can be especially prone to maladaptive responses to anxiety
provoking situations. For many of these, traditional non-pharmacologic behavior
management strategies may often prove inadequate or inappropriate to overcome
resistive or uncooperative behaviors. The importance of intervention with non
aversive techniques that provide a safe, child-oriented environment and timely
opportunity in which to encounter and cope with fear-producing situations cannot
be dismissed. The use of sedation techniques can frequently serve to obtund
interfering and potentially harmful behaviors to safely permit quality care,
minimize or eliminate the need for aversive measures, and help bridge the
transition for a child lacking cooperative ability to the time when cooperation
potential develops.
PMID- 17042449
TI - Easing the grip of patients' fear.
PMID- 17042450
TI - You had to be there to believe it!
PMID- 17042451
TI - Hurricanes' aftermath lingers on.
PMID- 17042452
TI - New standards emphasize emotional well-being.
PMID- 17042453
TI - Top 50 nursing facility chains & top 40 assisted living chains.
PMID- 17042454
TI - A case for consistent assignment.
PMID- 17042455
TI - Inviting lifestyles, caring people.
PMID- 17042456
TI - Depression and the MDS.
PMID- 17042457
TI - QIOS assist in the transfer to technology.
PMID- 17042458
TI - Shedding a new light on chronic ailments.
PMID- 17042459
TI - Keeping influenza in check.
PMID- 17042460
TI - Constructing a building contract.
PMID- 17042461
TI - VA shapes new telehealth model.
PMID- 17042462
TI - Holistic and biomedical concepts of health: a study of health notions among
Swedish occupational therapists and a suggestion for developing an instrument for
comparative studies.
AB - The objectives of this study were to inquire into notions of health among a group
of 439 Swedish occupational therapists and to test a model derived from a
qualitative study by Bjorklund & Svensson with a representative sample of
occupational therapists in Sweden. The data were collected through a
questionnaire and were analyzed using descriptive statistics, cluster analysis,
and confirmatory factor analysis. The means and ranking of the health notions
showed that Swedish occupational therapists most frequently hold holistic notions
of health, and to a lesser extent biostatistical ones. Most Swedish occupational
therapists indicate that being clearly conscious of one's health notions is
important both to themselves and to their profession. The test of the model
provides a step towards developing an instrument for measuring notions of health
that clearly distinguishes between holistic and biomedical ones and that could
possibly be used for comparative studies.
PMID- 17042463
TI - Occupational therapists' reflection on practice within psychiatric care: a Delphi
study.
AB - AIM: The aim of this study was to describe the reflections on practice in a group
of Swedish occupational therapists in psychiatric care in order to illuminate the
present practice and ideas about the future using a Delphi survey of three
rounds. MATERIAL AND METHOD: The sample consisted of 14 occupational therapists
in psychiatric care. The answers from the first and second rounds illustrate the
wide variation in their practice. The third round points out consensus and
disagreements in the domains: professional role, theories in practice, domain of
concern, occupational therapy assessment, goal setting/treatment,
outcome/evaluation and thoughts about the future. A consensus was reached in all
domains, but not regarding competence to treat functional reduction and symptoms,
or on the importance of theories for documentation, the choice of a theoretical
foundation, and the importance of an evidence-based treatment model, although the
theories were seen as supporting practice. Disagreements were found as to the
effectiveness of repeated assessments as a means of evaluation. The future for
OTs within psychiatric care was looked upon as positive. DISCUSSION: The results
developed from providing a relatively unclear and shallow perspective on OT
practice to indicating a depth that shows what occupational therapy within
psychiatry can be. During the process it became more and more clear how OTs think
and act.
PMID- 17042464
TI - Leaving homelessness and addiction: narratives of an occupational transition.
AB - The aim of this exploratory study was to gain an understanding of occupational
aspects of homelessness and of the transition from homelessness. Data were
collected through narrative interviews of two formerly homeless women recovering
from drug addiction. Data were analyzed using a constant comparative method
followed by a narrative analysis. The findings first identified homelessness as a
life of high intensity lived within a limited time perspective. Further, for
these women homelessness was related to drug addiction, which was experienced at
first as a solution to life situations that seemed impossible to handle. Second,
the analysis showed how social relationships can strengthen or change the lived
plots of the participants. Third, the transition out of homelessness was
accomplished through the development and enactment of new lived plots. Finally
the analysis showed that life as formerly homeless women was experienced as less
intense and as a life that can only partly be controlled. This new life includes
a broader time perspective. In the discussion, the relationship between time use
and the meaning-making process and possible practical implications of this study
are presented.
PMID- 17042465
TI - Experiences within the process of sick leave.
AB - The aim of this study was to explore what individuals who have been on sick leave
experienced as important in the process of returning to work, moving to long-term
sick leave, or receiving a disability pension. Grounded Theory was used for
interpreting interviews with 15 people who had been on sick leave four years
previously. In the results four ideal types were crystallized which are presented
in the form of vignettes. The ideal types were discussed focusing on occupational
life using the Model of Human Occupation and the theories of Sense of Coherence
and Status Passage. The study provided a deeper understanding of people's
experiences during the process of their sick leave. Valuable predictors for re
entry into work or disability retirement were: individual mental resources; clear
or unclear diagnosis; how long had been spent in the sick-leave process; and
personal belief in an ability to work in the future. The interventions and
support given by professionals and the social environment, the balance and sense
of coherence in life, and participation in the sick leave process were also
important. The idealtypes found could be helpful to professionals working in this
field in deepening their understanding of the clients.
PMID- 17042466
TI - Spinal cord injured persons' conceptions of hospital care, rehabilitation, and a
new life situation.
AB - BACKGROUND: The basic aim of spinal cord injury (SCI) rehabilitation is to help
patients return to a life worth living. It is therefore important that the staff
at spinal units and rehabilitation centres understand how the patients experience
their rehabilitation and their adjustment process to the new situation. AIM: To
describe SCI persons' experiences of their rehabilitation process. METHOD:
Nineteen SCI persons were interviewed. Data from the tape-recorded interviews
were analysed according to a modified descriptive version of the phenomenographic
analysis process. RESULTS: Six categories that describe the informants'
conceptions of their rehabilitation process emerged: access to information,
participation in planning rehabilitation, emotional support, feelings of
vulnerability, adjustment to a new life situation, and emotional consequences of
the injury. CONCLUSION: Straightforward information, participation in the
planning of the rehabilitation programme and emotional support were important
factors influencing the rehabilitation process after the SCI. Professionals
working with SCI rehabilitation should make use of patients' experiences in order
to develop better rehabilitation programmes that focus on the individual needs of
the patient. People are individuals and failure to take this into account can
impact negatively on quality of life and the effectiveness of the rehabilitation.
PMID- 17042467
TI - Life satisfaction in early rheumatoid arthritis: a prospective study.
AB - The aim of this study was to describe life satisfaction prospectively in patients
with early rheumatoid arthritis (RA) and to investigate its correlation with
disease activity. The early RA group was compared with RA patients with
longstanding disease and with a reference group. Gender differences were also
compared. Patients with early RA, treated by a multidisciplinary team, reported
their life satisfaction by completing a questionnaire. Disease activity score,
patient global assessment, and pain were scored at onset of disease and after two
years. The patients with early RA were less satisfied with life as a whole at
disease onset compared with the reference group, as was a cohort of patients with
longstanding disease. Patients with early RA also reported low levels of
satisfaction with self-care activities, work, and sexual life. The women reported
themselves more satisfied than men. After two years, a slight increase in the
reported levels of satisfaction could be seen for life as a whole and for five of
the eight domains. No correlation was found between disease activity variables
and satisfaction with life as a whole. There were, however, positive correlations
between disease activity and satisfaction both with partnership and with family
life after two years, i.e. the higher disease activity the higher satisfaction
with partnership relation and family life. In contrast, patients with greater
disease activity were less satisfied with self-care activities. The results of
this study indicate that greater effort is needed to assist patients with early
RA to cope with problems concerning self-care activities, sexual life, and work.
PMID- 17042468
TI - Cooperative binding and multiple recognition by bridged bis(beta-cyclodextrin)s
with functional linkers.
AB - Possessing two beta-cyclodextrin cavities in close vicinity and a functional
linker with good structural variety in a single molecule, bridged bis(beta
cyclodextrin)s can significantly enhance the original binding ability and
molecular selectivity of native beta-cyclodextrin and thus be successfully
utilized in drug carriers, solubilizers, catalysis, photochemical materials, etc.
This Account describes recent developments in the intramolecular cooperative
binding and multiple recognition of bridged bis(beta-cyclodextrin)s with
functional linkers in solution, as well as their molecular assembly behaviors
through the intermolecular cooperative binding. It also gives a description of
unique properties and wide applications of bis(beta-cyclodextrin)s and their
assemblies.
PMID- 17042469
TI - Alpha-c-galactosylceramides: synthesis and immunology.
AB - The immunostimulant activity of alpha-galactosylceramides provided the impetus
for the research described here. The activity was first discovered via screening
of extracts of a marine sponge. The active materials purified from the extracts
were alpha-O-galactosylceramides. The work described herein focuses on syntheses
of alpha-C-galactosylceramides. Crucial methodologies for the syntheses were (i)
Ramberg-Backlund reaction, (ii) modified Julia olefination, (iii) olefin cross
metathesis, and (iv) Sharpless asymmetric epoxidation in four independent routes.
The immunostimulant activity of the synthetic alpha-C-galactosylceramide far
surpasses that of the O-galactosyl material. A discussion of the reasons for the
difference in activity is presented.
PMID- 17042470
TI - Polymer-induced flip-flop in biomembranes.
AB - This Account describes the ability of amphiphilic polymers (e.g., EO/PO/EO block
copolymers) and polycations [e.g., quaternized poly(4-vinylpyridine)] to
accelerate translocation from the inside leaflet to the outside leaflet ("flip
flop") within vesicle bilayer membranes. Driving forces and mechanisms of flip
flop catalyzed by the nonionic and cationic polymers are different. The nonionics
are bound to the biological membrane via incorporation of their hydrophobic
blocks into the inner part of the lipid bilayer occupied by the hydrocarbon
chains. The resulting scrambling of lipid molecules is favored by the overall
hydrophobicity of the copolymer and the volume of its hydrophobic block. External
binding of the cationic polymers, on the other hand, is driven by electrostatic
interactions between the positively charged polymer units and the negatively
charged lipid headgroups within the outside leaflet. Electrostatic binding favors
both the flip-flop of anionic lipid from the inner to outer leaflet and the
formation of anionic domains in the outer leaflet. When it is considered that
less than 1% of the liposome surface is occupied by certain bound polymers, their
effect upon membrane dynamics, as will be described herein, is considerable. A
distinct correlation has been found between the "flippase" activity of the
polymers and their ability to mediate drug permeation through biomembranes.
PMID- 17042471
TI - P-Phos: a family of versatile and effective atropisomeric dipyridylphosphine
ligands in asymmetric catalysis.
AB - This Account outlines our efforts in the design and synthesis of a family of
highly effective atropisomeric dipyridylphosphine ligands (P-Phos and its
variants) and in the development of their widespread applications in transition
metal-catalyzed asymmetric reactions including hydrogenation, hydrosilylation,
and C-C bond formation. Desirable attributes, such as air stability, broad
substrate scope, fast rates of reaction, excellent enantioselectivities, low
catalyst loading, and mild conditions, make the catalyst systems highly
attractive and thus may provide excellent opportunities for practical
applications.
PMID- 17042472
TI - Metallo-beta-lactamases: novel weaponry for antibiotic resistance in bacteria.
AB - Metallo-beta-lactamases are broad-spectrum zinc enzymes, able to inactivate most
clinically useful beta-lactam antibiotics. Their structural and functional
diversity has thus far limited the understanding of their catalytic mechanism,
therefore thwarting the rational design of a common inhibitor. On the basis of
the recent availability of structures of enzyme-product complexes and novel
mechanistic studies, here, we attempt to find minimal common elements in
different members of this family. In contrast with other metalloenzymes, most of
the substrate binding and catalytic power resides in the adequate positioning of
one or two Zn(II) ions in the active site, empowered by an unusual flexibility.
PMID- 17042473
TI - Modeling enzymatic reactions involving transition metals.
AB - High-accuracy quantum chemistry has now been applied for almost 10 years to
biological problems involving transition metal active sites. The leading
theoretical method is hybrid density functional theory (DFT), usually with the
B3LYP functional. The chemical models vary in size, commonly from 30 to 100 atoms
treated fully quantum mechanically. Two schools exist, one using the smallest
possible adequate models and the other using as large models as possible and
sometimes including the entire enzyme by combining quantum mechanics with
molecular mechanics. In our group, we have found that the latter approach, which
is much more time-consuming and error prone, is seldom needed. In this Account,
methods and models will be described and examples of recent applications given.
The examples are chosen to illustrate trends and to show cases where theory has
predicted new mechanisms not suggested previously.
PMID- 17042474
TI - Catalytically active gold: from nanoparticles to ultrathin films.
AB - Ordered gold (Au) mono- and bilayer structures have been synthesized on a highly
reduced titania surface. The Au bilayer exhibits a significantly higher catalytic
activity for carbon monoxide oxidation than does the Au monolayer structure. This
is the first report of Au completely wetting an oxide surface and demonstrates
that ultrathin Au films on an oxide surface have exceptionally high catalytic
activity, comparable to the activity observed for Au nanoparticles. This
discovery is a key to understanding the nature of the active site of supported Au
catalysts.
PMID- 17042475
TI - Predicting the stereochemistry of diphenylphosphino benzoic acid (DPPBA)-based
palladium-catalyzed asymmetric allylic alkylation reactions: a working model.
AB - Palladium-catalyzed asymmetric allylic alkylation has proven to be a powerful
method for the preparation of a wide variety of chiral compounds and the rapid
assembly of complex molecular architecture from simple starting materials. While
many types of catalyst systems have been successfully employed with certain
systems, diphenylphosphino benzoic acid (DPPBA) based ligands have found use over
a broad range of substrate classes. This Account highlights the mechanistic
aspects considered when designing reactions with DPPBA-based ligands and presents
a working model for the a priori prediction of their stereochemical outcome.
PMID- 17042476
TI - Super radical stabilizers.
AB - A comprehensive series of substituted 1,1-dimethyl-2-methylenecyclopropanes have
been thermally rearranged. These rearrangements proceed via singlet biradical
intermediates that can be stabilized by substituents. Rates are greatly enhanced
by certain groups that are termed super radical stabilizers. Substituents
included 4-pyridyl N-oxide, 2-(1,6-methano[10]annulenyl), and a number of anion
substituted phenyl groups. Simple valence bond theory, as well as more
sophisticated computational studies, gives insights into modes of radical
stabilization.
PMID- 17042477
TI - How do low-energy (0.1-2 eV) electrons cause DNA-strand breaks?
AB - We overview our recent theoretical predictions and the innovative experimental
findings that inspired us concerning the mechanisms by which very low-energy (0.1
2 eV) free electrons attach to DNA and cause strong (ca. 4 eV) covalent bonds to
break causing so-called single-strand breaks. Our primary conclusions are that
(i) attachment of electrons in the above energy range to base pi* orbitals is
more likely than attachment elsewhere and (ii) attachment to base pi* orbitals
most likely results in cleavage of sugar-phosphate C-O sigma bonds. Later
experimental findings that confirmed our predictions about the nature of the
electron attachment event and about which bonds break when strand breaks form are
also discussed. The proposed mechanism of strand break formation by low-energy
electrons involves an interesting through-bond electron-transfer process.
PMID- 17042478
TI - Antibodies with infinite affinity: origins and applications.
AB - Antibodies with infinite affinity were developed with the aim of improving
targeted delivery of metal complexes to sites of disease. This is part of a
series of chemical technology developments for biomedical imaging and therapy.
Using a combination of genetics and chemical synthesis, it addresses challenges
in developing proteins that specifically bind synthetic molecules and do not
release them. The result is a set of reagents that promise to capture any of a
large variety of metallic elements under physiological conditions and hold them
for long periods of time.
PMID- 17042479
TI - Structural and electron paramagnetic resonance (EPR) studies of mononuclear
molybdenum enzymes from sulfate-reducing bacteria.
AB - Molybdenum and tungsten are found in biological systems in a mononuclear form in
the active site of a diverse group of enzymes that generally catalyze oxygen-atom
transfer reactions. The metal atom (Mo or W) is coordinated to one or two
pyranopterin molecules and to a variable number of ligands such as oxygen (oxo,
hydroxo, water, serine, aspartic acid), sulfur (cysteines), and selenium
(selenocysteines) atoms. In addition, these proteins contain redox cofactors such
as iron-sulfur clusters and heme groups. All of these metal cofactors are along
an electron-transfer pathway that mediates the electron exchange between
substrate and an external electron acceptor (for oxidative reactions) or donor
(for reductive reactions). We describe in this Account a combination of
structural and electronic paramagnetic resonance studies that were used to reveal
distinct aspects of these enzymes.
PMID- 17042480
TI - Enantiomeric free radicals and enzymatic control of stereochemistry in a radical
mechanism: the case of lysine 2,3-aminomutases.
AB - The product of yjeK in Escherichia coli is a homologue of lysine 2,3-aminomutase
(LAM) from Clostridium subterminale SB4, and both enzymes catalyze the
isomerization of (S)- but not (R)-alpha-lysine by radical mechanisms. The
turnover number for LAM from E. coli is 5.0 min(-1), 0.1% of the value for
clostridial LAM. The reaction of E. coli LAM with (S)-alpha-[3,3,4,4,5,5,6,6
(2)H8]lysine proceeds with a kinetic isotope effect (kH/kD) of 1.4, suggesting
that hydrogen transfer is not rate-limiting. The product of the E. coli enzyme is
(R)-beta-lysine, the enantiomer of the clostridial product. Beta-lysine-related
radicals are observed in the reactions of both enzymes by electron paramagnetic
resonance (EPR). The radical in the reaction of clostridial LAM has the (S)
configuration, whereas that in the reaction of E. coli LAM has the (R)
configuration. Moreover, the conformations of the beta-lysine-related radicals at
the active sites of E. coli and clostridial LAM are different. The nuclear
hyperfine splitting between the C3 hydrogen and the unpaired electron at C2 shows
the dihedral angle to be 6 degrees, unlike the value of 77 degrees reported for
the analogous radical bound to the clostridial enzyme. Reaction of (S)-4
thialysine produces a substrate-related radical in the steady state of E. coli
LAM, as in the action of the clostridial enzyme. While (S)-beta-lysine is not a
substrate for E. coli LAM, it undergoes hydrogen abstraction to form an (S)-beta
lysine-related radical with the same stereochemistry of hydrogen transfer from C2
of (S)-beta-lysine to the 5'-deoxyadenosyl radical as in the action of the
clostridial enzyme. The resulting beta-lysyl radical has a conformation different
from that at the active site of clostridial LAM. All evidence indicates that the
opposite stereochemistry displayed by E. coli LAM is determined by the
conformation of the lysine side chain in the active site. Stereochemical models
for the actions of LAM from C. subterminale and E. coli are presented.
PMID- 17042481
TI - Identification of structural and catalytic classes of highly conserved amino acid
residues in lysine 2,3-aminomutase.
AB - Lysine 2,3-aminomutase (LAM) from Clostridium subterminale SB4 catalyzes the
interconversion of (S)-lysine and (S)-beta-lysine by a radical mechanism
involving coenzymatic actions of S-adenosylmethionine (SAM), a [4Fe-4S] cluster,
and pyridoxal 5'-phosphate (PLP). The enzyme contains a number of conserved
acidic residues and a cysteine- and arginine-rich motif, which binds iron and
sulfide in the [4Fe-4S] cluster. The results of activity and iron, sulfide, and
PLP analysis of variants resulting from site-specific mutations of the conserved
acidic residues and the arginine residues in the iron-sulfide binding motif
indicate two classes of conserved residues of each type. Mutation of the
conserved residues Arg134, Asp293, and Asp330 abolishes all enzymatic activity.
On the basis of the X-ray crystal structure, these residues bind the epsilon
aminium and alpha-carboxylate groups of (S)-lysine. However, among these
residues, only Asp293 appears to be important for stabilizing the [4Fe-4S]
cluster. Members of a second group of conserved residues appear to stabilize the
structure of LAM. Mutations of arginine 130, 135, and 136 and acidic residues
Glu86, Asp165, Glu236, and Asp172 dramatically decrease iron and sulfide contents
in the purified variants. Mutation of Asp96 significantly decreases iron and
sulfide content. Arg130 or Asp172 variants display no detectable activity,
whereas variants mutated at the other positions display low to very low
activities. Structural roles are assigned to this latter class of conserved amino
acids. In particular, a network of hydrogen bonded interactions of Arg130, Glu86,
Arg135, and the main chain carbonyl groups of Cys132 and Leu55 appears to
stabilize the [4Fe-4S] cluster.
PMID- 17042482
TI - Structure of testis ACE glycosylation mutants and evidence for conserved domain
movement.
AB - Human angiotensin-converting enzyme is an important drug target for which little
structural information has been available until recent years. The slow progress
in obtaining a crystal structure was due to the problem of surface glycosylation,
a difficulty that has thus far been overcome by the use of a glucosidase-1
inhibitor in the tissue culture medium. However, the prohibitive cost of these
inhibitors and incomplete glucosidase inhibition makes alternative routes to
minimizing the N-glycan heterogeneity desirable. Here, glycosylation in the
testis isoform (tACE) has been reduced by Asn-Gln point mutations at N
glycosylation sites, and the crystal structures of mutants having two and four
intact sites have been solved to 2.0 A and 2.8 A, respectively. Both mutants show
close structural identity with the wild-type. A hinge mechanism is proposed for
substrate entry into the active cleft, based on homology to human ACE2 at the
levels of sequence and flexibility. This is supported by normal-mode analysis
that reveals intrinsic flexibility about the active site of tACE. Subdomain II,
containing bound chloride and zinc ions, is found to have greater stability than
subdomain I in the structures of three ACE homologues. Crystallizable
glycosylation mutants open up new possibilities for cocrystallization studies to
aid the design of novel ACE inhibitors.
PMID- 17042483
TI - Architecture of a gamma retroviral genomic RNA dimer.
AB - Retroviral genomes contain two sense-strand RNAs that are noncovalently linked at
their 5' ends, forming a dimer. Establishing a structure for this dimer is an
obligatory first step toward understanding the fundamental role of the dimeric
RNA in retroviral biology. We developed a secondary structure model for the
minimal dimerization active sequence (MiDAS) for the Moloney murine sarcoma virus
in the final dimer state using selective 2'-hydroxyl acylation analyzed by primer
extension (SHAPE). In this model, two self-complementary, or palindromic,
sequences (PAL1 and PAL2) form extended intermolecular duplexes of 10 and 16 base
pairs, respectively. The monomeric starting state was shown previously to contain
a flexible domain in which nucleotides do not form stable interactions with other
parts of the RNA. In the final dimer state, portions of this initial flexible
domain form stable base pairs, while previously base-paired elements lie in a new
flexible domain. Thus, partially overlapping and structurally well-defined
flexible domains are prominent features of both monomer and dimer states. We then
used hydroxyl radical cleavage experiments to characterize the global
architecture of the dimer state. Extensive regions, including portions of both
PAL1 and PAL2, are occluded from solvent-based cleavage indicating that the MiDAS
domain does not function simply as a collection of autonomous secondary structure
elements. Instead, the retroviral dimerization domain adopts a compact
architecture characterized by close packing of its constituent helices.
PMID- 17042484
TI - A hyperthermophilic protein acquires function at the cost of stability.
AB - Active-site residues are not often optimized for conformational stability
(activity-stability trade-offs) in proteins from organisms that grow at moderate
temperature. It is unknown if the activity-stability trade-offs can be applied to
proteins from hyperthermophiles. Because enzymatic activity usually increases at
higher temperature and hyperthermophilic proteins need high conformational
stability, they might not sacrifice the stability for their activity. This study
attempts to clarify the contribution of active-site residues to the
conformational stability of a hyperthermophilic protein. We therefore examined
the thermodynamic stability and enzymatic activity of wild-type and active-site
mutant proteins (D7N, E8A, E8Q, D105A, and D135A) of ribonuclease HII from
Thermococcus kodakaraensis (Tk-RNase HII). Guanidine hydrochloride (GdnHCl)
induced denaturation was measured with circular dichroism at 220 nm, and heat
induced denaturation was studied with differential scanning calorimetry. Both
GdnHCl- and heat-induced denaturation were highly reversible in these proteins.
All the mutations of these active-site residues, except that of Glu8 to Gln,
reduced the enzymatic activity dramatically but increased the protein stability
by 7.0 to 11.1 kJ mol(-1) at 50 degrees C. The mutation of Glu8 to Gln did not
seriously affect the enzymatic activity and increased the stability only by 2.5
kJ mol(-1) at 50 degrees C. These results indicate that hyperthermophilic
proteins also exhibit the activity-stability trade-offs. Therefore, the
architectural mechanism for hyperthermophilic proteins is equivalent to that for
proteins at normal temperature.
PMID- 17042485
TI - Role of the S128, H186, and N187 triad in substrate binding and decarboxylation
in the sheep liver 6-phosphogluconate dehydrogenase reaction.
AB - Crystal structures of 6-phosphogluconate dehydrogenase (6PGDH) from sheep liver
indicate that S128 and N187 are within hydrogen-bonding distance of 6PG in the
E:6PG binary complex and NADPH in the E:NADPH binary complex. In addition, H186
is also within hydrogen-bonding distance of NADPH in the E:NADPH binary complex,
while in the E:6PG binary complex it is within hydrogen-bonding distance of S128
and close to N187. The structures suggest that this triad of residues may play a
dual role during the catalytic reaction. Site-directed mutagenesis has been
performed to mutate each of the three residues to alanine. All mutant enzymes
exhibit a decrease in V/E(t) (the turnover number), ranging from 7- to 67-fold.
An increase in the Km for 6PG (K(6PG)) was observed for S128A and H187A mutant
enzymes, while for the H186A mutation, K(6PG) is decreased by a factor of 2.
K(NADP) remains the same as the wild type enzyme for the S128A and H186A mutant
enzyme, while it increases by 6-fold in the N187A mutant enzyme. An increased
K(iNADPH) was measured for all of the mutant enzymes. The primary kinetic 13C
isotope effect is increased, while the primary deuterium kinetic isotope effect
is decreased, indicating that the decarboxylation step has become more rate
limiting under conditions where substrate is limiting. A quantitative analysis of
the data suggests that the S128, H186, and N187 triad is multifunctional in the
6PGDH reaction and contributes as follows. The triad (1) participates in the
precatalytic conformational change; (2) provides ground state binding affinity
for 6PG and NADPH; and (3) affects the relative rates of reduction or
decarboxylation of the 3-keto-6PG intermediate by anchoring the cofactor after
hydride transfer, which is accompanied by the rotation of the nicotinamide ring
around the N-glycosidic bond and displacement of C1 of 6PG, facilitating
decarboxylation.
PMID- 17042486
TI - Crystal structures of the Synechocystis photoreceptor Slr1694 reveal distinct
structural states related to signaling.
AB - Crystal structures of the Synechocystis BLUF phototaxis photoreceptor Slr1694
have been determined in two crystal forms, a monoclinic form at 1.8 A resolution
and an orthorhombic form at 2.1 A resolution. In both forms, the photoreceptor is
comprised of two pentamer rings stacked face to face. Twenty total subunits in
the two asymmetric units of these crystal forms display three distinct tertiary
structures that differ in the length of the fifth beta-strand and in the
orientation of Trp91, a conserved Trp residue near the FMN chromophore.
Fluorescence spectroscopic analysis on Slr1694 in solution is consistent with
motion of Trp91 from a hydrophobic environment in the dark state to a more
hydrophilic environment in the light-excited state. Mutational analysis indicates
that movement of Trp91 is dependent on the occupancy of the hydrophobic Trp
binding pocket with a nearby Met. These different tertiary structures may be
associated with absorption changes in the blue region of the spectrum.
PMID- 17042487
TI - The inhibitor protein (IF1) promotes dimerization of the mitochondrial F1F0-ATP
synthase.
AB - The effect of increased expression or reconstitution of the mitochondrial
inhibitor protein (IF1) on the dimer/monomer ratio (D/M) of the rat liver and
bovine heart F1F0-ATP synthase was studied. The 2-fold increased expression of
IF1 in AS-30D hepatoma mitochondria correlated with a 1.4-fold increase in the
D/M ratio of the ATP synthase extracted with digitonin as determined by blue
native electrophoresis and averaged densitometry analyses. Removal of IF1 from
rat liver or bovine heart submitochondrial particles increased the F1F0-ATPase
activity and decreased the D/M ratio of the ATP synthase. Reconstitution of
recombinant IF1 into submitochondrial particles devoid of IF1 inhibited the F1F0
ATPase activity by 90% and restored partially the D/M ratio of the whole F1F0
complex as revealed by blue native electrophoresis and subsequent SDS-PAGE or
glycerol density gradient centrifugation. Thus, the inhibitor protein promotes or
stabilizes the dimeric form of the intact F1F0-ATP synthase. A possible location
of the IF1 protein in the dimeric structure of the rat liver F1F0 complex is
proposed. According to crystallographic and electron microscopy analyses, dimeric
IF1 could bridge the F1-F1 part of the dimeric F1F0-ATP synthase in the inner
mitochondrial membrane.
PMID- 17042488
TI - Structure of the membrane reconstituted transmembrane-juxtamembrane peptide
EGFR(622-660) and its interaction with Ca2+/calmodulin.
AB - The transmembrane (TM) and juxtamembrane (JM) regions of the epidermal growth
factor receptor (EGFR) couple ligand binding in the extracellular domain to
activation of the kinase domain. Solid-state NMR and polarized FTIR measurements
of peptides corresponding to the TM plus JM regions of EGFR (residues 622-660)
reconstituted in model phospholipid membranes are presented to address the role
of the short cytoplasmic JM sequence (residues 645-660) in regulating EGFR
activity. We show that the TM domain is helical with a transition to non-helical
structure at the TM-JM boundary. Fluorescence measurements indicate that the JM
region of EGFR(622-660) binds to the membrane surface and that binding can be
reversed by the addition of the complex of Ca2+ and calmodulin. Together these
data support models suggesting the cytoplasmic JM region of EGFR plays an active
role in regulating receptor activity.
PMID- 17042489
TI - Role of threonine 101 on the stability of the heme active site of cytochrome
P450cam: multiwavelength circular dichroism studies.
AB - The role of the threonine 101 residue that resides close to the heme propionic
acid side chain of cytochrome P450cam on the conformational properties of the
active site of the enzyme has been investigated by circular dichroism (CD)
spectroscopy. Site-specific mutation of the threonine by valine has been carried
out that does not affect the size of the residue but significantly alters the
hydropathy index. The T101V mutant of cytochrome P450cam showed distinct
differences in the CD spectra near the heme region, indicating a subtle effect of
the mutation on the properties of the heme active site. Thermal stabilities of
the mutant and wild-type enzyme have been studied by temperature dependence of
the ellipticity (intensity of the CD band) in the far-UV region for the secondary
structure and at different wavelengths in the visible region that arise from the
heme moiety for the tertiary structure around the prosthetic group. The thermal
unfolding data from variations of the CD intensity at different wavelengths were
analyzed using a generalized multistep unfolding model, and two distinct
equilibrium intermediate conformational states of the enzyme were identified. The
mutation of the T101 residue by valine was found to decrease the thermal
stability of both the intermediates in the presence of the substrate. On the
other hand, this mutation had no apparent effect on the thermal stability of the
enzyme in the absence of the substrate. These results suggested that the
threonine residue stabilizes the protein cavity around the heme center in the
case of the substrate-bound species, possibly by hydrogen bonding with one of the
propionate side chains of the heme moiety. Such hydrogen bonding of the heme
propionate with threonine is absent in the substrate-free form of the enzyme.
PMID- 17042490
TI - Binding of polyaminocarboxylate chelators to the active-site copper inhibits the
GSNO-reductase activity but not the superoxide dismutase activity of Cu,Zn
superoxide dismutase.
AB - In addition to its superoxide dismutase (SOD) activity, Cu,Zn-superoxide
dismutase (CuZnSOD) catalyzes the reductive decomposition of S-nitroso-L
glutathione (GSNO) in the presence of thiols such as L-glutathione (GSH). The
GSNO-reductase activity but not the superoxide dismutase (SOD) activity of
CuZnSOD is inhibited by the commonly used polyaminocarboxylate metal ion
chelators, EDTA and DTPA. The basis for this selective inhibition is
systematically investigated here. Incubation with EDTA or DTPA caused a time
dependent decrease in the 680 nm d-d absorption of Cu(II)ZnSOD but no loss in SOD
activity or in the level of metal loading of the enzyme as determined by ICP-MS.
The chelators also protected the SOD activity against inhibition by the arginine
specific reagent, phenylglyoxal. Measurements of both the time course of SNO
absorption decay at 333 nm and oxymyoglobin scavenging of the NO that is released
confirmed that the chelators inhibit CuZnSOD catalysis of GSNO reductive
decomposition by GSH. The decreased GSNO-reductase activity is correlated with
decreased rates of Cu(II)ZnSOD reduction by GSH in the presence of the chelators
as monitored spectrophotometrically at 680 nm. The aggregate data suggest binding
of the chelators to CuZnSOD, which was detected by isothermal titration
calorimetry (ITC). Dissociation constants of 0.08 +/- 0.02 and 8.3 +/- 0.2 microM
were calculated from the ITC thermograms for the binding of a single EDTA and
DTPA, respectively, to the CuZnSOD homodimer. No association was detected under
the same conditions with the metal-free enzyme (EESOD). Thus, EDTA and DTPA must
bind to the solvent-exposed active-site copper of one subunit without removing
the metal. This induces a conformational change at the second active site that
inhibits the GSNO-reductase but not the SOD activity of the enzyme.
PMID- 17042491
TI - Time-resolved FTIR difference spectroscopy for the study of photosystem I
particles with plastoquinone-9 occupying the A1 binding site.
AB - In photosystem I from plants and cyanobacteria a phylloquinone molecule, called
A1, functions as the secondary electron acceptor. In cyanobacteria, genes that
encode for proteins involved in phylloquinone biosynthesis can be deleted. Here,
we have studied three different gene deletion mutants called menB, menD, and menE
mutants. In these mutants, plastoquinone-9 occupies the A1 binding site. Using
time-resolved, step-scan FTIR difference spectroscopy we have produced A1(-)/A1
FTIR difference spectra for menB, menD, and menE photosystem I particles at 77 K.
These difference spectra show that the P700 triplet state ((3)P700) is formed in
a large fraction of the particles. Infrared spectral signatures that are not due
to (3)P700 are also observed in the spectra and are suggested to be associated
with plastoquinone-9 anion formation in a portion of the particles. By
subtracting the known (3)P700 spectral signatures, we produce an A1(-)/A1 FTIR
difference spectrum for PS I particles with plastoquinone-9 occupying the binding
site. This spectrum shows that a band that we have previously assigned to a C:-O
mode of the phylloquinone anion in WT A1(-)/A1 FTIR DS down-shifts approximately
8 cm(-1) when plastoquinone-9 occupies the A1 binding site. Using density
functional theory type calculations to produce anion minus neutral infrared
difference spectra for both phylloquinone and plastoquinone-9, it is shown that
such a downshift is reasonable. A1(-)/A1 FTIR difference spectra, obtained using
menB mutant photosystem I particles that were incubated in the presence of
phylloquinone, are found to be very similar to those obtained using normal WT
photosystem I particles. This result indicates that we were able to reincorporate
phylloquinone back into the A1 binding site and that the reincorporated
phylloquinone and its immediate protein environment, in both the neutral and
anion state, are very similar to that found in wild type photosystem I particles.
For the reconstituted menB mutant photosystem I particles, no spectral signatures
associated with (3)P700 are observed, indicating that phylloquinone occupies the
A1 site in all of the reconstituted menB particles.
PMID- 17042492
TI - Structural basis of the ferrous iron specificity of the yeast ferroxidase, Fet3p.
AB - Fet3p is a multicopper oxidase (MCO) that functions together with the iron
permease, Ftr1p, to support high-affinity Fe uptake in yeast. Fet3p is a
ferroxidase that, like ceruloplasmin and hephaestin, couples the oxidation of 4
equiv of Fe(II) to the reduction of O2 to 2 H2O. The ferrous iron specificity of
this subclass of MCO proteins has not been delineated by rigorous structure
function analysis. Here the crystal structure of Fet3p has been used as a
template to identify the amino acid residues that confer this substrate
specificity and then to quantify the contributions they make to this specific
reactivity by thermodynamic and kinetic analyses. In terms of the Marcus theory
of outer-sphere electron transfer, we show here that D283, E185, and D409 in
Fet3p provide a Fe(II) binding site that actually favors ferric iron; this site
thus reduces the reduction potential of the bound Fe(II) in comparison to that of
aqueous ferrous iron, providing a thermodynamically more robust driving force for
electron transfer. In addition, E185 and D409 constitute parts of the electron
transfer pathway from the bound Fe(II) to the protein's type 1 Cu(II). This
electronic matrix coupling relies on H-bonds from the carboxylate OD2 atom of
each residue to the NE2 NH group of the two histidine ligands at the type 1 Cu
site. These two acidic residues and this H-bond network appear to distinguish a
fungal ferroxidase from a fungal laccase since the specificity that Fet3p has for
Fe(II) is completely lost in a Fet3pE185A/D409A mutant. Indeed, this double
mutant functions kinetically better as a laccase, albeit a relatively inefficient
one.
PMID- 17042493
TI - Redox thermodynamics of the Fe(III)/Fe(II) couple of human myeloperoxidase in its
high-spin and low-spin forms.
AB - Myeloperoxidase (MPO) (donor, hydrogen peroxide oxidoreductase, EC 1.11.1.7) is
the most abundant neutrophil enzyme and catalyzes predominantly the two-electron
oxidation of ubiquitous chloride (Cl-), to generate the potent bleaching oxidant
hypochlorous acid (HOCl), thus contributing to bacterial killing and inflammatory
reactions of neutrophils. Here, the thermodynamics of the one-electron reduction
of the ferric heme in its ferric high-spin and cyanide-bound low-spin forms were
determined through spectroelectrochemical experiments. The E(o)' values for free
and cyanide-bound MPO (5 and -37 mV, respectively, at 25 degrees C and pH 7.0)
are significantly higher than those of other heme peroxidases. Variable
temperature experiments revealed that the enthalpic stabilization of ferric high
spin MPO is much weaker than in other heme peroxidases and is exactly compensated
by the entropic change upon reduction. In contrast to those of other heme
peroxidases, the stabilization of the ferric cyanide-bound MPO is also very weak
and fully entropic. This peculiar behavior is discussed with respect to the MPO
typical covalent heme to protein linkages as well as to the published structures
of ferric MPO and its cyanide complex and the recently published structure of
lactoperoxidase as well as the physiological role of MPO in bacterial killing.
PMID- 17042494
TI - Facile detection of acyl and peptidyl intermediates on thiotemplate carrier
domains via phosphopantetheinyl elimination reactions during tandem mass
spectrometry.
AB - With the emergence of drug resistance and the genomic revolution, there has been
a renewed interest in the genes that are responsible for the generation of
bioactive natural products. Secondary metabolites of one major class are
biosynthesized at one or more sites by ultralarge enzymes that carry covalent
intermediates on phosphopantetheine arms. Because such intermediates are
difficult to characterize in vitro, we have developed a new approach for
streamlined detection of substrates, intermediates, and products attached to a
phosphopantetheinyl arm of the carrier site. During vibrational activation of gas
phase carrier domains, facile elimination occurs in benchtop and Fourier
transform mass spectrometers alike. Phosphopantetheinyl ejections quickly reduce
>100 kDa megaenzymes to <1000 Da ions for structural assignment of intermediates
at <0.007 Da mass accuracy without proteolytic digestion. This "top down"
approach quickly illuminated diverse acyl intermediates on the carrier domains of
the nonribosomal peptide synthetases (NRPSs) or polyketide synthases (PKSs) found
in the biosynthetic pathways of prodigiosin, pyoluteorin, mycosubtilin,
nikkomycin, enterobactin, gramicidin, and several proteins from the orphan pksX
gene cluster from Bacillus subtilis. By focusing on just those regions undergoing
covalent chemistry, the method delivered clean proof for the reversible
dehydration of hydroxymethylglutaryl-S-PksL via incorporation of 2H or 18O from
the buffer. The facile nature of this revised assay will allow diverse
laboratories to spearhead their NRPS-PKS projects with benchtop mass
spectrometers.
PMID- 17042495
TI - Delayed release of inorganic phosphate from elongation factor Tu following GTP
hydrolysis on the ribosome.
AB - The dissociation of inorganic phosphate (P(i)) following GTP hydrolysis is a key
step determining the functional state of many GTPases. Here, the timing of P(i)
release from elongation factor Tu (EF-Tu) and its implications for the function
of EF-Tu on the ribosome were studied by rapid kinetic techniques. It was found
that P(i) release from EF-Tu is >20-fold slower than GTP cleavage and limits the
rate of the conformational switch of EF-Tu from the GTP- to the GDP-bound form.
The point mutation Gly94Ala in the switch 2 region of EF-Tu abolished the delay
in P(i) release, suggesting that P(i) release is controlled by the mobility of
the switch 2 region with Gly94 acting as a pivot. The rate of P(i) release or the
conformational switch of EF-Tu does not affect the selection of aminoacyl-tRNA on
the ribosome. Rather, the slow P(i) release may be a consequence of the tight
interaction of the switch regions of EF-Tu with the gamma-phosphate and the
ribosome in the GTPase activated state of the factor.
PMID- 17042496
TI - Direct kinetic evidence for half-of-the-sites reactivity in the E1 component of
the human pyruvate dehydrogenase multienzyme complex through alternating sites
cofactor activation.
AB - Recent kinetic and structural studies on various thiamin-dependent enzymes,
including the bacterial E1 component of the pyruvate dehydrogenase complex
(PDHc), suggested an active center communication between the cofactors in these
multimeric enzymes. This regulatory mode has been inferred from the dissymmetry
of active sites in proteolytic patterns and X-ray structures and from a complex
macroscopic kinetic behavior not being consistent with independently working
active sites. Here, direct microscopic kinetic evidence for this hypothesis is
presented for the alpha2beta2-type E1 component of the human pyruvate
dehydrogenase complex. Only one of the two thiamin molecules bound to the two
active sites is in a chemically activated state exhibiting an apparent C2
ionization rate constant of approximately 50 s(-1) at pH 7.6 and 30 degrees C,
whereas the thiamin in the "inactive site" ionizes with a rate that is at least 3
orders of magnitude smaller. The chemical nonequivalence is also exhibited in the
ability to bind the substrate analogue methyl acetylphosphonate and in the
catalytic turnover of the substrate pyruvate in the E1-only reaction. In the
activated active site, pyruvate is rapidly bound and decarboxylated with apparent
forward rate constants of covalent pyruvate binding of 2 s(-1) and
decarboxylation of the formed 2-lactyl-thiamin intermediate of 5 s(-1). In the
dormant site, these steps are as slow as 0.03 s(-1). Under the conditions that
were used, only the heterotetramer can be detected by analytical
ultracentrifugation, thus ruling out the possibility that multiple oligomeric
species with different reactivities cause the observed kinetic effects. The
results are consistent with the recently suggested model of an active site
synchronization in PDHc-E1 via a proton wire that keeps the two active sites in
an alternating activation state [Frank, R. A., et al. (2004) Science 306, 872].
Kinetic studies on the related thiamin enzymes transketolase, pyruvate oxidase,
and bacterial pyruvate decarboxylase are not consistent with a chemical and/or
functional nonequivalence of the active sites as observed in the E1 component of
hsPDHc. We hypothesize that the alternating sites reaction in PDHc-E1 aids in the
synchronized acyl transfer to the E2 component in the highly organized
multienzyme complex.
PMID- 17042497
TI - Chimeric thermostable DNA polymerases with reverse transcriptase and attenuated
3'-5' exonuclease activity.
AB - The synthesis of accurate, full-length cDNA from low-abundance RNA and the
subsequent PCR amplification under conditions which provide amplicon that
contains minimal mutations remain a difficult molecular biological process. Many
of the challenges associated with performing sensitive, long RT/PCR have been
alleviated by using a mixture of DNA polymerases. These mixtures have typically
contained a DNA polymerase devoid of 3'-5' exonuclease, or "proofreading",
activity blended with a small amount of an Archaea DNA polymerase possessing 3'
5' exonuclease activity, since reverse transcriptases lack 3'-5' exonuclease
activity and generally have low fidelity. To create a DNA polymerase with
efficient reverse transcriptase and 3'-5' exonuclease activity, a family of
mutant DNA polymerases with a range of attenuated 3'-5' exonuclease activities
was constructed from a chimeric DNA polymerase derived from Thermus species Z05
and Thermotoga maritima DNA polymerases. These "designer" DNA polymerases were
fashioned using structure-based tools to identify amino acid residues involved in
the substrate-binding site of the exonuclease domain of a thermostable DNA
polymerase. Mutation of some of these residues resulted in proteins in which DNA
polymerase activity was unaffected, while proofreading activity ranged from 60%
of the wild-type level to undetectable levels. Kinetic characterization of the
exonuclease activity indicated that the mutations affected catalysis much more
than binding. On the basis of their specificity constants (kcat/KM), the mutant
enzymes have a 5-15-fold stronger preference for a double-stranded mismatched
substrate over a single-stranded substrate than the wild-type DNA polymerase, a
desirable attribute for RT/PCR. The utility of these enzymes was evaluated in a
RT/PCR assay to generate a 1.7 kb amplicon from HIV-1 RNA.
PMID- 17042498
TI - Structure and function of prokaryotic glutamate transporters from Escherichia
coli and Pyrococcus horikoshii.
AB - The glutamate transporters GltP(Ec) from Escherichia coli and GltP(Ph) from
Pyrococcus horikoshii were overexpressed in E. coli and purified to homogeneity
with a yield of 1-2 mg/L of culture. Single-particle analysis and electron
microscopy indicate that GltP(Ph) is a trimer in detergent solution. Electron
microscopy of negatively stained GltP(Ph) two-dimensional crystals shows that the
transporter is a trimer also in the membrane. Gel filtration of GltP(Ec)
indicates a reversible equilibrium of two oligomeric states in detergent solution
that we identified as a trimer and hexamer by blue-native gel electrophoresis and
cross-linking. The purified transporters were fully active upon reconstitution
into liposomes, as demonstrated by the uptake of radioactively labeled L
aspartate or L-glutamate. L-aspartate/L-glutamate transport of GltP(Ec) involves
the cotransport of protons and depends only on pH, whereas GltP(Ph) catalyzes L
glutamate transport with a cotransport of H+ or Na+. L-glutamate induces a fast
transient current in GltP(Ph) proteoliposomes coupled to a solid supported
membrane (SSM). We show that the electric signal depends on the concentration of
Na+ or H+ outside the proteoliposomes and that GltP(Ph) does not require K+
inside the proteoliposomes. In addition, the electrical currents are inhibited by
TBOA and HIP-B. The half-saturation concentration for activation of GltP(Ph)
glutamate transport (K0.5(glut)) is 194 microM.
PMID- 17042499
TI - Nature and significance of the interactions between amyloid fibrils and
biological polyelectrolytes.
AB - Charged polyelectrolytes such as glycosaminoglycans and nucleic acids have
frequently been found associated with the proteinaceous deposits in the tissues
of patients with amyloid diseases. We have investigated the nature and generality
of this phenomenon by studying the ability of different polyanions, including
DNA, ATP, heparin, and heparan sulfate, to promote the aggregation of
amyloidogenic proteins and to bind to the resulting aggregates. Preformed amyloid
fibrils of human muscle acylphosphatase and human lysozyme, proteins with a net
positive charge at physiological pH values, were found to bind tightly to the
negatively charged DNA or ATP. The effects of the polyelectrolytes on the
kinetics of aggregation were studied for acylphosphatase, and the presence of
ATP, DNA, or heparin was found to increase its aggregation rate dramatically,
with a degree dependent on the net charge and size of the polyanion. Magnesium or
calcium ions were found to attenuate, and ultimately to suppress, these
interactions, suggesting that they are electrostatic in nature. Moreover, heparin
was found to stabilize the aggregated state of acylphosphatase through
compensation of electrostatic repulsion. Noteworthy, differences in affinity
between native and aggregated acylphosphatase with heparin suggest that amyloid
fibrils can themselves behave as polyelectrolytes, interacting very strongly with
other polyelectrolytes bearing the opposite charge. Within an in vivo context,
the strengthening of the electrostatic interactions with other biological
polyelectrolytes, as a consequence of protein misfolding and aggregation, could
therefore result in depletion of essential molecular components and contribute to
the known cytotoxicity of amyloid fibrils and their precursors.
PMID- 17042500
TI - Gene selection, alternative splicing, and post-translational processing regulate
neuroligin selectivity for beta-neurexins.
AB - Neuroligins 1-4 are postsynaptic transmembrane proteins capable of initiating
presynaptic maturation via interactions with beta-neurexin. Both neuroligins and
beta-neurexins have alternatively spliced inserts in their extracellular domains.
Using analytical ultracentrifugation, we determined that the extracellular
domains of the neuroligins sediment as dimers, whereas the extracellular domains
of the beta-neurexins appear monomeric. Sedimentation velocity experiments of
titrated stoichiometry ratios of beta-neurexin and neuroligin suggested a 2:2
complex formation. The recognition properties of individual neuroligins toward
beta-neurexin-1 (NX1beta), along with the influence of their splice inserts, were
explored by surface plasmon resonance and affinity chromatography. Different
neuroligins display a range of NX1beta affinities spanning more than 2 orders of
magnitude. Whereas splice insert 4 in beta-neurexin appears to act only as a
modulator of the neuroligin/beta-neurexin association, splice insert B in
neuroligin-1 (NL1) is the key element regulating the NL1/NX1beta binding. Our
data indicate that gene selection, mRNA splicing, and post-translational
modifications combine to give rise to a controlled neuroligin recognition code
with a rank ordering of affinities for particular neurexins that is conserved for
the neuroligins across mammalian species.
PMID- 17042501
TI - A single gamma-carboxyglutamic acid residue in a novel cysteine-rich secretory
protein without propeptide.
AB - Gamma-glutamyl carboxylase catalyzes the modification of specific glutamyl
residues to gamma-carboxyglutamyl (Gla) residues in precursor proteins that
possess the appropriate gamma-carboxylation recognition signal within the
propeptide region. We describe the immunopurification and first biochemical
characterization of an invertebrate high molecular weight Gla-containing protein
with homologues in mammals. The protein, named GlaCrisp, was isolated from the
venom of the marine cone snail Conus marmoreus. GlaCrisp gave intense signals in
Western blot experiments employing the Gla-specific antibody M3B, and the
presence of Gla was chemically confirmed by amino acid analysis after alkaline
hydrolysis. Characterization of a full-length cDNA clone encoding GlaCrisp
deduced a precursor containing an N-terminal signal peptide but, unlike other Gla
containing proteins, no apparent propeptide. The predicted mature protein of 265
amino acid residues showed considerable sequence similarity to the widely
distributed cysteine-rich secretory protein family and closest similarity (65%
identity) to the recently described substrate-specific protease Tex31. In
addition, two cDNA clones encoding the precursors of two isoforms of GlaCrisp
were identified. The predicted precursor isoforms differed at three amino acid
positions (-6, 9, and 25). Analysis by Edman degradation and nanoelectrospray
ionization mass spectrometry, before and after methyl esterfication, identified a
Gla residue at amino acid position 9 in GlaCrisp. This is the first example of a
Gla-containing protein without an obvious gamma-carboxylation recognition site.
The results define a new class of Gla proteins and support the notion that gamma
carboxylation of glutamyl residues is phylogenetically older than blood
coagulation and the vertebrate lineage.
PMID- 17042502
TI - Multiple interactions of FbsA, a surface protein from Streptococcus agalactiae,
with fibrinogen: affinity, stoichiometry, and structural characterization.
AB - Streptococcus agalactiae is an etiological agent of several infective diseases in
humans. We previously demonstrated that FbsA, a fibrinogen-binding protein
expressed by this bacterium, elicits a fibrinogen-dependent aggregation of
platelets. In the present communication, we show that the binding of FbsA to
fibrinogen is specific and saturable, and that the FbsA-binding site resides in
the D region of fibrinogen. In accordance with the repetitive nature of the
protein, we found that FbsA contains multiple binding sites for fibrinogen. By
using several biophysical methods, we provide evidence that the addition of FbsA
induces extensive fibrinogen aggregation and has noticeable effects on thrombin
catalyzed fibrin clot formation. Fibrinogen aggregation was also found to depend
on FbsA concentration and on the number of FbsA repeat units. Scanning electron
microscopy evidentiated that, while fibrin clot is made of a fine fibrillar
network, FbsA-induced Fbg aggregates consist of thicker fibers organized in a
cage-like structure. The structural difference of the two structures was further
indicated by the diverse immunological reactivity and capability to bind tissue
type plasminogen activator or plasminogen. The mechanisms of FbsA-induced
fibrinogen aggregation and fibrin polymerization followed distinct pathways since
Fbg assembly was not inhibited by GPRP, a specific inhibitor of fibrin
polymerization. This finding was supported by the different sensitivity of the
aggregates to the disruptive effects of urea and guanidine hydrochloride. We
suggest that FbsA and fibrinogen play complementary roles in contributing to
thrombogenesis associated with S. agalactiae infection.
PMID- 17042503
TI - Functional homodimers and heterodimers of recombinant smooth muscle tropomyosin.
AB - Skeletal and smooth muscle tropomyosin (Tm) require acetylation of their N
termini to bind strongly to actin. Tm containing an N-terminal alanine-serine
(AS) extension to mimic acetylation has been widely used to increase binding. The
current study investigates the ability of an N-terminal AS extension to mimic
native acetylation for both alpha alpha and beta beta smooth Tm homodimers. We
show that (1) AS alpha-Tm binds actin 100-fold tighter than alpha-Tm and 2-fold
tighter than native smooth alphabeta-Tm, (2) beta-Tm requires an AS extension to
bind actin, and (3) AS beta-Tm binds actin 10-fold weaker than AS alpha-Tm. Tm is
present in smooth muscle tissues as >95% heterodimer; therefore, we studied the
binding of recombinant alphabeta heterodimers with different AS extensions. This
study shows that recombinant Tm requires an AS extension on both alpha and beta
chains to bind like native Tm and that the alpha chain contributes more to actin
binding than the beta chain. Once assembled onto an actin filament, all smooth
muscle Tm's regulate S1 binding to actin Tm in the same way, irrespective of the
presence of an AS extension.
PMID- 17042504
TI - N-terminal fragments of tau inhibit full-length tau polymerization in vitro.
AB - The polymerization of the microtubule-associated protein, tau, into insoluble
filaments is a common thread in Alzheimer's disease and in a variety of
frontotemporal dementias. The conformational change required for tau to
transition from an extended monomeric state to a filamentous state with a high
beta-sheet content involves the extreme N-terminus coming into contact with
distal portions of the molecule; however, these exact interactions are
incompletely understood. Here we report that a construct representing amino acids
1-196 (Tau196), which itself does not polymerize, inhibits polymerization of full
length tau (hTau40) in vitro. In addition, we trace the inhibitory effect of
Tau196 to amino acids 18-42 of the construct. We also provide evidence that the N
terminal tau fragments require a specific C-terminal region of tau (residues 392
421) to exert their inhibitory effect. The fragments are most effective at
inhibiting polymerization when present during the initial 5 min; they remain in
the soluble fraction of the polymerization reaction, and they increase the amount
of soluble hTau40. The fragments also reduce the number and average length of
filaments that are formed. Taken together, these results suggest that the N
terminal tau fragments inhibit hTau40 polymerization by interacting with a
specific C-terminal sequence, thereby stabilizing a soluble conformation of tau.
PMID- 17042505
TI - Characterization of the heme binding properties of Staphylococcus aureus IsdA.
AB - We report the first characterization of the physical and spectroscopic properties
of the Staphylococcus aureus heme-binding protein IsdA. In this study, a
combination of gel filtration chromatography and analytical centrifugation
experiments demonstrate that IsdA, in solution, is a monomer and adopts an
extended conformation that would suggest that it has the ability to protrude from
the staphylococcal cell wall and interact with the extracellular environment.
IsdA efficiently scavenged intracellular heme within Escherichia coli. Gel
filtration chromatography and electrospray mass spectrometry together showed that
rIsdA in solution is a monomer, and each monomer binds a single heme. Magnetic
circular dichroism analyses demonstrate that the heme in rIsdA is a five
coordinate high-spin ferric heme molecule, proximally coordinated by a tyrosyl
residue in a cavity that restricts access to small ligands. The heme binding is
unlike that in a typical heme protein, for example, myoglobin, because we report
that no additional axial ligation is possible in the high-spin ferric state of
IsdA. However, reduction to ferrous heme is possible which then allows CO to
axially ligate to the ferrous iron. Reoxidation forms the ferric heme, which is
once again isolated from exogenous ligands. In summary, rIsdA binds a five
coordinate, high-spin ferric heme which is proximally coordinated by tyrosine.
Reduction results in formation of five-coordinate, high-spin ferrous heme with a
neutral axial ligand, most likely a histidine. Subsequent addition of CO results
in a six-coordinate low-spin ferrous heme also with histidine likely bound
proximally. Reoxidation returns the tyrosine as the proximal ligand.
PMID- 17042506
TI - Spectroscopic evidence for Ca2+ involvement in the assembly of the Mn4Ca cluster
in the photosynthetic water-oxidizing complex.
AB - Biogenesis and repair of the inorganic core (Mn4CaO(x)Cl(y)), in the water
oxidizing complex of photosystem II (WOC-PSII), occurs through the light-induced
(re)assembly of its free elementary ions and the apo-WOC-PSII protein, a reaction
known as photoactivation. Herein, we use electron paramagnetic resonance (EPR)
spectroscopy to characterize changes in the ligand coordination environment of
the first photoactivation intermediate, the photo-oxidized Mn3+ bound to apo-WOC
PSII. On the basis of the observed changes in electron Zeeman (g(eff)), 55Mn
hyperfine (A(Z)) interaction, and the EPR transition probabilities, the
photogenerated Mn3+ is shown to exist in two pH-dependent forms, differing in
terms of strength and symmetry of their ligand fields. The transition from an EPR
invisible low-pH form to an EPR-active high-pH form occurs by deprotonation of an
ionizable ligand bound to Mn3+, implicated to be a water molecule: [Mn3+ (OH2)] <
-> [Mn3+ (OH-)]. In the absence of Ca2+, the EPR-active Mn3+ exhibits a strong pH
dependence (pH approximately 6.5-9) of its ligand-field symmetry (rhombicity
Delta delta = 10%, derived from g(eff)) and A(Z) (DeltaA(Z) = 22%), attributable
to a protein conformational change. Binding of Ca2+ to its effector site
eliminates this pH dependence and locks both g(eff) and A(Z) at values observed
in the absence of Ca2+ at alkaline pH. Thus, Ca2+ directly controls the
coordination environment and binds close to the high-affinity Mn3+, probably
sharing a bridging ligand. This Ca2+ effect and the pH-induced changes are
consistent with the ionization of the bridging water molecule, predicting that
[Mn3+-(mu-O(-2))-Ca2+] or [Mn3+-(mu-OH(-))2-Ca2+] is the first light intermediate
in the presence of Ca2+. The formation of this intermediate templates the apo-WOC
PSII for the subsequent rapid cooperative binding and photo-oxidation of three
additional Mn2+ ions, forming the active water oxidase.
PMID- 17042507
TI - A mass spectrometry-based probe of equilibrium intermediates in protein-folding
reactions.
AB - Described here is a mass spectrometry- and H/D exchange-based approach for the
detection of equilibrium intermediate state(s) in protein-folding reactions. The
approach utilizes the stability of unpurified proteins from rates of H/D exchange
(SUPREX) technique to measure the m value (i.e., delta DeltaG/delta [denaturant]
value) associated with the folding reaction of a protein. Such SUPREX m-value
analyses can be made over a wide range of denaturant concentrations. Thus, the
described approach is well-suited for the detection of high-energy intermediates
that might be populated at low denaturant concentrations and hard to detect in
conventional chemical denaturation experiments using spectroscopic probes. The
approach is demonstrated on four known non-two-state folding proteins, including
alpha-lactalbumin, cytochrome c, intestinal fatty acid binding protein (IFABP),
and myoglobin. The non-two-state folding behavior of each model protein system
was detected by the described method. The cytochrome c, myoglobin, and IFABP
systems each had high-energy intermediate states that were undetected in
conventional optical spectroscopy-based studies and previously required other
more specialized biophysical approaches (e.g., nuclear magnetic resonance
spectroscopy-based methods and protease protection assays) for their detection.
The SUPREX-based approach outlined here offers an attractive alternative to these
other approaches, because it has the advantage of speed and the ability to
analyze both purified and unpurified protein samples in either concentrated or
dilute solution.
PMID- 17042508
TI - Replication-coupled repair of crotonaldehyde/acetaldehyde-induced guanine-guanine
interstrand cross-links and their mutagenicity.
AB - The repair of acetaldehyde/crotonaldehyde-induced guanine (N2)-guanine (N2)
interstrand cross-links (ICLs), 3-(2-deoxyribos-1-yl)-5,6,7,8-(N2-deoxyguanosyl)
6(R or S)-methylpyrimido[1,2-alpha]purine-10(3H)-one, was studied using a shuttle
plasmid bearing a site-specific ICL. Since the authentic ICLs can revert to
monoadducts, a chemically stable model ICL, 1,3-bis(2'-deoxyguanos-N2-yl)butane
derivative, was also employed to probe the ICL repair mechanism. Since the
removal of ICL depends on the nucleotide excision repair (NER) mechanism in
Escherichia coli, the plasmid bearing the model ICL failed to yield transformants
in NER-deficient host cells, proving the stability of this ICL in cells. The
authentic ICLs yielded transformants in the NER-deficient hosts; therefore, these
transformants are produced by plasmid bearing spontaneously reverted monoadducts.
In contrast, in NER-deficient human cells, the model ICL was removed by an NER
independent repair pathway, which is unique to higher eukaryotes. This repair did
not associate with a transcriptional event, but with replication. The analysis of
repaired molecules revealed that the authentic and model ICLs were repaired
mostly (>94%) in an error-free manner in both hosts. The major mutations that
were observed were G --> T transversions targeting the cross-linked dG located in
the lagging strand template. These results support one of the current models for
the mammalian NER-independent ICL repair mechanism, in which a DNA
endonuclease(s) unhooks an ICL from the leading strand template at a stalled
replication fork site by incising on both sides of the ICL and then translesion
synthesis is conducted across the "half-excised" ICL attached to the lagging
strand template to restore DNA synthesis.
PMID- 17042509
TI - Potent lectin-independent chaperone function of calnexin under conditions
prevalent within the lumen of the endoplasmic reticulum.
AB - Calnexin is a membrane-bound chaperone of the endoplasmic reticulum (ER) that
participates in the folding and quality control of newly synthesized
glycoproteins. Binding to glycoproteins occurs through a lectin site with
specificity for Glc1Man9GlcNAc2 oligosaccharides as well as through a polypeptide
binding site that recognizes non-native protein conformations. The latter
interaction is somewhat controversial because it is based on observations that
calnexin can suppress the aggregation of non-glycosylated substrates at elevated
temperature or at low calcium concentrations, conditions that may affect the
structural integrity of calnexin. Here, we examine the ability of calnexin to
interact with a non-glycosylated substrate under physiological conditions of the
ER lumen. We show that the soluble ER luminal domain of calnexin can indeed
suppress the aggregation of non-glycosylated firefly luciferase at 37 degrees C
and at the normal resting ER calcium concentration of 0.4 mM. However, gradual
reduction of calcium below the resting level was accompanied by a progressive
loss of native calnexin structure as assessed by thermal stability, protease
sensitivity, intrinsic fluorescence, and bis-ANS binding. These assays permitted
the characterization of a single calcium binding site on calnexin with a Kd =
0.15 +/- 0.05 mM. We also show that the suppression of firefly luciferase
aggregation by calnexin is strongly enhanced in the presence of millimolar
concentrations of ATP and that the Kd for ATP binding to calnexin in the presence
of 0.4 mM calcium is 0.7 mM. ATP did not alter the overall stability of calnexin
but instead triggered the localized exposure of a hydrophobic site on the
chaperone. These findings demonstrate that calnexin is a potent molecular
chaperone that is capable of suppressing the aggregation of substrates through
polypeptide-based interactions under conditions that exist within the ER lumen.
PMID- 17042510
TI - On the stability of miniemulsions in the presence of RAFT agents.
AB - The colloidal stability of miniemulsions in the presence of RAFT or other control
agents for controlled free radical polymerization is examined. A derivation,
based on Lifshitz-Slyozov-Wagner (LSW) theory, is proposed here to evaluate the
effect of a RAFT agent on the diffusional stability of the miniemulsions before
the onset of polymerization. Results indicate that, depending on the
hydrophobicity of the control agent, its presence may augment or detract from the
effectiveness of the costabilizer in preventing diffusional instability due to
Ostwald ripening.
PMID- 17042511
TI - Surface-enhanced Raman scattering on molecular self-assembly in nanoparticle
hydrogel composite.
AB - Surface-enhanced Raman scattering has been applied to study weak intermolecular
interactions between small organic gelling molecules involved in the silver
nanoparticle-hydrogel composite formation. Assembly and disassembly of the
gelator molecules in close vicinity to embedded silver nanoparticles were
followed by changes in Raman intensity of the amide II and carboxyl vibrational
bands, whereas the strength of the bands related to benzene modes remained
constant. This implied that the gelator molecules were strongly attached to the
silver particles through the benzene units, while participating in gel structure
organization by intermolecular hydrogen bonding between oxalyl amide and carboxyl
groups.
PMID- 17042512
TI - Molecular dynamics investigation of bent-core molecules on a water surface.
AB - Molecular dynamics simulations are carried out for bent-core molecules at water
surfaces. The water surface is shown to alter the equilibrium molecular structure
significantly by causing a different class of torsional states to become more
favorable. The equilibrium structure is also altered by the substitution of
chlorine atoms for hydrogen atoms on the central phenyl ring in that this
substitution forces the bent core to remain in a single torsional state rather
than be delocalized among several torsional states. The consequences of these
structural changes on the chirality and packing of these molecules on water
surfaces are discussed.
PMID- 17042513
TI - Electrochemical capacitances of well-defined carbon surfaces.
AB - Reported is the capacitive behavior of homogeneous and well-defined surfaces of
pristine carbon nanofibers (CNFs) and surface-modified CNFs. The capacitances of
the well-defined CNFs were measured with cyclic voltammetry to correlate the
surface structure with capacitance. Among the studied pristine CNFs, the edge
surfaces of platelet CNFs (PCNF) and herringbone CNFs were more effective in
capacitive charging than the basal plane surface of tubular CNF by a factor of 3
5. Graphitization of PCNF (GPCNF) changed the edge surface of PCNF into a
domelike basal plane surface, and the corresponding capacitances decreased from
12.5 to 3.2 F/g. A chemical oxidation of the GPCNF, however, recovered a clear
edge surface by removal of the curved basal planes to increase the capacitance to
5.6 F/g. The difference in the contribution of the edge surface and basal-plane
surface to the capacitance of CNF was discussed in terms of the anisotropic
conductivity of graphitic materials.
PMID- 17042514
TI - Patterning amyloid peptide fibrils by AFM charge writing.
AB - Surface charge patterns generated by atomic force microscopy-based charge writing
were used to pattern amyloid-like peptide fibrils on a solid substrate. Fibrils
of the short peptide TTR105-115 were encapsulated inside water droplets of a
water-in-perfluorocarbon oil emulsion and retained their rod morphology. They
were observed to deposit selectively with a lateral resolution of approximately 1
microm onto negatively charged patterns on a polymethyl-methacrylate substrate.
PMID- 17042515
TI - Biomimetic growth of silica tubes in confined media.
AB - Polymer membranes were used as biomimetic environments to study the effect of
confinement on silica formation. Within membrane pores, silica tubes were formed,
consisting of a dense silica shell incorporating nanoparticle aggregates. The
shell structure does not depend on the membrane pore size, suggesting that its
formation proceeds via interfacial interactions with the pore surface. In
contrast, the size of primary nanoparticles within core aggregates is influenced
by pore dimensions, indicating an effect of confinement on the diffusion-limited
growth of silica. A parallel can be drawn with reported roles of confinement in
biomineralization processes, providing a basis for future developments in
biosilicification mimetic approaches and biofunctional nanomaterials design.
PMID- 17042516
TI - Lipid diffusion in giant unilamellar vesicles is more than 2 times faster than in
supported phospholipid bilayers under identical conditions.
AB - The lateral diffusion coefficients of a BODIPY tail-labeled lipid in two model
systems, namely, free-standing giant unilamellar vesicles (GUVs) and supported
phospholipid bilayers (SPBs), were determined by fluorescence correlation
spectroscopy (FCS) using the Z-scan approach. For the first time, the performed
measurements on 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers maintain
exactly the same experimental conditions for both systems, which allows for a
quantitative comparison of lipid diffusion in these two commonly used model
membranes. The results obtained revealed that the lipid mobility in free-standing
bilayers (D=7.8+/-0.8 microm2 s-1) is significantly higher than in the bilayer
created on the solid support (mica) (D=3.1+/-0.3 microm2 s-1).
PMID- 17042517
TI - Supramolecular dynamics studied using photophysics.
AB - Dynamics is an essential feature of supramolecular systems, and it's
understanding will be central in achieving new chemical function. The methodology
to obtain association and dissociation rate constants for fast binding of guests
to host systems in real time is described. Examples are provided for binding of
guests to cyclodextrins or bile salt aggregates with an emphasis on the type of
information and mechanistic insight that can only be uncovered from kinetic
studies and is not apparent in thermodynamic investigations.
PMID- 17042518
TI - Effect of surfactant conformation on the structures of small size nonionic
reverse micelles: a molecular dynamics simulation study.
AB - We used constant pressure (P=0.1 MPa) and temperature (T=298 K) molecular
dynamics simulations to study the structures and dynamics of small size reverse
micelles (RMs) with poly(ethylene glycol) alkyl ether (CmEn) surfactants. The
water-to-surfactant molar ratio was 3, with decane as the apolar solvent. We
focused on the effect of the two possible imposed conformations (trans vs gauche)
for the surfactant headgroups on RMs structures and water dynamics. For this
purpose, we built up two RMs, which only differ by their surfactant headgroup
conformations. The results obtained for the two RMs were compared to what is
known in the literature. Here, we show that the surfactant headgroup conformation
affects mainly the water-related properties such as the water core size, the area
per surfactant headgroup, the headgroup hydration, and the water core
translational diffusion. The properties computed for the RM with the surfactant
in trans conformation fit better with the experimental data than the gauche
conformation. We further show that the surfactant hydrophilic headgroup plays a
crucial role in the micellar structures, favors the entrapment of the micellar
water, and reduces strongly their diffusion compared to the bulk water.
PMID- 17042519
TI - Depletion interaction mediated by a polydisperse polymer studied with total
internal reflection microscopy.
AB - Total internal reflection microscopy (TIRM) was applied to measure depletion
forces between a charged colloidal sphere and a charged solid wall induced by
dextran, a nonionic nonadsorbing polydisperse polysaccharide. The polymer size
polydispersity is shown to greatly influence the depletion potential. Using the
theory for the depletion interaction due to ideal polydisperse polymer chains, we
could accurately describe the experimental data with a single adjustable
parameter.
PMID- 17042520
TI - Clouding and phase behavior of nonionic surfactants in hydrophobically modified
hydroxyethyl cellulose solutions.
AB - Clouding phenomena and phase behaviors of two nonionic surfactants, Triton X-114
and Triton X-100, in the presence of either hydroxyethyl cellulose (HEC) or its
hydrophobically modified counterpart (HMHEC) were experimentally studied.
Compared with HEC, HMHEC was found to have a stronger effect on lowering the
cloud point temperature of a nonionic surfactant at low concentrations. The
difference in clouding behavior can be attributed to different kinds of molecular
interactions. Depletion flocculation is the underlying mechanism in the case of
HEC, while the chain-bridging effect is responsible for the large decrease of
cloud point for HMHEC. Composition analyses for the formed macroscopic phases
were carried out to provide support for associative phase separation for the case
of HMHEC, in contrast to segregative phase separation for HEC. An interesting
three-phase-separation phenomenon was reported in some HMHEC/Triton X-100
mixtures at high surfactant concentrations.
PMID- 17042521
TI - Fabrication of colloidal doublets by a salting out-quenching-fusing technique.
AB - It is well-known that high ionic strength promotes colloid aggregation. Here we
show that, by controlling this aggregation process, we can produce high yields of
homodoublet and heterodoublet polymer colloids. The aggregation process is
started by increasing the ionic strength to roughly 250 mM KCl. After
approximately the rapid flocculation time, we quench the "reaction" by mixing in
a large quantity of deionized water, which dilutes the ionic strength and
prevents further aggregation. At this point, the suspension consists primarily of
singlet and doublet particles. Through heating above the glass transition
temperature of the polymers, the doublets are fused together and remain intact
even after sonication. It is also shown that heterodoublets can include a silica
particle together with a polymer colloid. The salting out-quenching-fusing
technique is a rapid, easy-to-perform, repeatable process for fabricating
colloidal doublets from polymers and other materials.
PMID- 17042522
TI - Diffusion of platinum ions and platinum nanoparticles during photoreduction
processes using the transient grating method.
AB - The photoreduction process of PtCl(6)2- to Pt nanoparticles in poly(N-vinyl-2
pyrrolidone) solutions upon UV light irradiation was investigated by monitoring
the change in the diffusion coefficient (D). The D values of chemical species
during UV irradiation was measured by the laser-induced transient grating (TG)
method. The TG signal of the PtCl(6)2- solution before UV irradiation was
composed of three kinds of contributions, the thermal grating, the species
grating due to the creation of PtCl4(2-), and the species grating due to the
depletions of PtCl6(2-). Upon UV irradiation of the solution, the species grating
signal due to PtCl6(2-) diminished and then the TG signal of Pt nanoparticles
gradually appeared. This result indicates that the gradual clustering of Pt0
atoms into Pt nanoparticles occurs after all PtCl(6)2- ions are photochemically
reduced to PtCl(4)2- and subsequently transformed to Pt0 atoms with a short
delay. With increasing time of the UV irradiation, the TG signal intensity
increased, while D of the Pt nanoparticles did not change. This suggests that the
number of Pt nanoparticles increases, but the size of the Pt nanoparticles with
the polymer layer is unchanged, in the course of the UV irradiation.
PMID- 17042523
TI - Electrostatically driven protein aggregation: beta-lactoglobulin at low ionic
strength.
AB - The aggregation of beta-lactoglobulin (BLG) at ambient temperature was studied
using turbidimetry and dynamic light scattering in the range 3.8W2.2-->W3.2-->W4lite-->W4 is proposed as a
converging hierarchy of computational thermochemistry methods. A simple a priori
estimate for the importance of post-CCSD(T) correlation contributions (and hence
a pessimistic estimate for the error in a W2-type calculation) is proposed.
PMID- 17042581
TI - The Jarzynski identity derived from general Hamiltonian or non-Hamiltonian
dynamics reproducing NVT or NPT ensembles.
AB - The Jarzynski identity (JI) relates nonequilibrium work averages to thermodynamic
free energy differences. It was shown in a recent contribution [M. A. Cuendet,
Phys. Rev. Lett. 96, 120602 (2006)] that the JI can, in particular, be derived
directly from the Nose-Hoover thermostated dynamics. This statistical mechanical
derivation is particularly relevant in the framework of molecular dynamics
simulation, because it is based solely on the equations of motion considered and
is free of any additional assumptions on system size or bath coupling. Here, this
result is generalized to a variety of dynamics, along two directions. On the one
hand, specific improved thermostating schemes used in practical applications are
treated. These include Nose-Hoover chains, higher moment thermostats, as well as
an isothermal-isobaric scheme yielding the JI in the NPT ensemble. On the other
hand, the theoretical generality of the new derivation is explored. Generic
dynamics with arbitrary coupling terms and an arbitrary number of thermostating
variables, both non-Hamiltonian and Hamiltonian, are shown to imply the JI. In
particular, a nonautonomous formulation of the generalized Nose-Poincare
thermostat is proposed. Finally, general conditions required for the JI
derivation are briefly discussed.
PMID- 17042582
TI - Effective multipoles and Yukawa electrostatics in dressed molecule theory.
AB - In this paper we derive the multipolar expansion of the screened Coulomb
potential in electrolyte solutions with molecular solvent. The solute and solvent
molecules can have arbitrary sizes, shapes, and internal charge distributions. We
use the exact statistical mechanical definition of renormalized charge
distributions coming from "dressed molecule theory" to determine the effective
multipoles of a molecule immersed in an electrolyte. The effects of many-body
correlations are fully included in our formally exact theory. We restrict
ourselves to sufficiently dilute solutions so the screened Coulomb potential
decays for large distances like a Yukawa function, exp(-kappa r)/r, where r is
the distance and 1/kappa is the decay length (it is normally different from the
Debye length). The resulting "Yukawa electrostatics" differ in many respects from
ordinary, unscreened electrostatics. The "Yukawa charge" of a molecule (the
lowest order moment in the multipolar expansion) is in general not equal to its
Coulombic charge and it is not the integral of the renormalized charge
distribution of the molecule. Moreover, as shown in this paper, the multipolar
expansion of the Yukawa potential does not correspond, contrary to the case of
the Coulomb potential, to its asymptotic expansion for large r. As a consequence,
the charge term in the multipolar expansion is not the leading term in the
asymptotic expansion. Instead, for large r values, multipoles of all orders
contribute to the leading asymptotic term. Thus, the electrostatic potential
from, for example, an electroneutral solvent molecule in an electrolyte solution
has generally the same range as that from an ion. The proper asymptotic expansion
for electrostatic interactions in electrolytes is derived. It is briefly shown
how the multipole expansion formalism can also be applied in the Poisson
Boltzmann approximation for primitive model electrolytes.
PMID- 17042583
TI - Analytic calculation of the diagonal Born-Oppenheimer correction within
configuration-interaction and coupled-cluster theory.
AB - Schemes for the analytic calculation of the diagonal Born-Oppenheimer correction
(DBOC) are formulated and implemented for use with general single-reference
configuration-interaction and coupled-cluster wave function models. Calculations
are reported to demonstrate the convergence of the DBOC with respect to electron
correlation treatment and basis set as well as to investigate the size
consistency error in configuration-interaction calculations of the DBOC. The
importance of electron-correlation contributions to the DBOC is illustrated in
the computation of the corresponding corrections for the reaction energy and
activation barrier of the F + H2 --> FH + H reaction as well as of the
atomization energy for trans-butadiene.
PMID- 17042584
TI - Photodissociation dynamics of fluorobenzene (C6H5F) at 157 and 193 nm: Branching
ratios and distributions of kinetic energy.
AB - Following photodissociation of fluorobenzene (C6H5F) at 193 and 157 nm, we
detected the products with fragmentation-translational spectroscopy by utilizing
a tunable vacuum ultraviolet beam from a synchrotron for ionization. Between two
primary dissociation channels observed upon irradiation at 193 (157) nm, the HF
elimination channel C6H5F --> HF + C6H4 dominates, with a branching ratio of
0.94+/-0.02 (0.61+/-0.05) and an average release of kinetic energy of 103 (108)
kJ mol(-1); the H-elimination channel C6H5F --> H + C6H4F has a branching ratio
of 0.06+/-0.02 (0.39+/-0.05) and an average release of kinetic energy of 18.6
(26.8) kJ mol(-1). Photofragments H, HF, C6H4, and C6H4F produced via the one
photon process have nearly isotropic angular distributions. Both the HF
elimination and the H-elimination channels likely proceed via the ground-state
electronic surface following internal conversion of C6H5F; these channels exhibit
small fractions of kinetic energy release from the available energy, indicating
that the molecular fragments are highly internally excited. We also determined
the ionization energy of C6H4F to be 8.6+/-0.2 eV.
PMID- 17042585
TI - The stability of allyl radicals following the photodissociation of allyl iodide
at 193 nm.
AB - The photodissociation of allyl iodide (C3H5I) at 193 nm was investigated by using
a combination of vacuum-ultraviolet photoionization of the allyl radical,
resonant multiphoton ionization of the iodine atoms, and velocity map imaging.
The data provide insight into the primary C-I bond fission process and into the
dissociative ionization of the allyl radical to produce C3H3+. The experimental
results are consistent with the earlier results of Szpunar et al. [J. Chem. Phys.
119, 5078 (2003)], in that some allyl radicals with internal energies higher than
the secondary dissociation barrier are found to be stable. This stability results
from the partitioning of available energy between the rotational and vibrational
degrees of freedom of the radical, the effects of a centrifugal barrier along the
reaction coordinate, and the effects of the kinetic shift in the secondary
dissociation of the allyl radical. The present results suggest that the primary
dissociation of allyl iodide to allyl radicals plus I*(2P(1/2)) is more important
than previously suspected.
PMID- 17042586
TI - Low frequency backbone vibrations of individual conformational isomers:
tryptamine.
AB - The low frequency vibrations of the ethylamino backbone of six conformers of
tryptamine have been studied in the ground and excited states using dispersed
fluorescence spectroscopy, rotationally resolved laser induced fluorescence, and
ab initio calculations. Four low frequency vibrational modes of the backbone,
which involve torsional and librational motions of the ethylamino group, have
been identified. The three anti conformers show a substantially different
vibrational pattern than the four conformers in which the amino group is in
gauche position with respect to the pyrrole and the phenyl ring, respectively.
PMID- 17042587
TI - Linear and nonlinear circular dichroism of R-(+)-3-methylcyclopentanone.
AB - Linear and nonlinear circular dichroism of R-(+)-3-methylcyclopentanone (R-3MCP)
is reported in the gas and liquid phases. Measurements of (2+1) resonance
enhanced multiphoton ionization circular dichroism (REMPICD) for nozzle-jet
expanded molecular beams of the equatorial conformer of R-3MCP are presented.
Monitoring either mass-selected cations or photoelectrons produced via (2+1)
REMPI through the n --> 3s Rydberg transition yielded a REMPICD of +1.5+/-0.5%
[REMPICD identical with 2(I(L)-I(R))(I(L)+I(R))], where I(L/R) refers to the
ion/electron signal for left/right circularly polarized light. A racemic mixture
of 3-methylcyclopentanone showed no significant CD; however, the signal
fluctuations were much larger than that observed for the resolved R-(+)-3
methylcyclopentanone as might be expected for the small number of ions produced
from slightly unequal numbers of enantiomers in each laser shot. Gas phase,
vibrationally resolved, one-photon CD for vapor phase R-(+)-3
methylcyclopentanone (i.e., admixture of five axial and equatorial forms) was
measured to be approximately 0 and -0.004 at photon energies corresponding to the
one- (nonresonant) and two-(3s resonance) photon energy levels. The one-photon CD
(of the room temperature population of conformers) at an energy corresponding to
the ionization step was measured previously to be approximately +0.0011 which is
of the same sign as the REMPICD. The first step is also near a positive CD
region. This suggests that the (2+1) REMPICD is determined primarily by both the
initial and continuum steps. The one-photon CDs for the equatorial and axial
forms of 3MCP are calculated, using GAUSSIAN03, to be approximately equal but
having opposite sign for the transitions of interest. The CD for 3MCP in
cyclohexane is found to be strongly temperature dependent as a result of the
presence of both the axial and equatorial conformers. The energy difference
between the two conformers is determined from a van't Hoff plot of these data to
be 3.50+/-0.05 kJ/mole in cyclohexane and is approximately 1 kJ/mole smaller than
measurements employing other methods.
PMID- 17042588
TI - Effects of microsolvation on uracil and its radical anion: uracil(H2O)n (n = 1
5).
AB - Microsolvation effects on the stabilities of uracil and its anion have been
investigated by explicitly considering the structures of complexes of uracil with
up to five water molecules at the B3LYPDZP++ level of theory. For all five
systems, the global minimum of the neutral cluster has a different equilibrium
geometry from that of the radical anion. Both the vertical detachment energy
(VDE) and adiabatic electron affinity (AEA) of uracil are predicted to increase
gradually with the number of hydrating molecules, qualitatively consistent with
experimental results from a photodetachment-photoelectron spectroscopy study [J.
Schiedt et al., Chem. Phys. 239, 511 (1998)]. The trend in the AEAs implies that
while the conventional valence radical anion of uracil is only marginally bound
in the gas phase, it will form a stable anion in aqueous solution. The gas-phase
AEA of uracil (0.24 eV) was higher than that of thymine by 0.04 eV and this gap
was not significantly affected by microsolvation. The largest AEA is that
predicted for uracil(H2O)5, namely, 0.96 eV. The VDEs range from 0.76 to 1.78 eV.
PMID- 17042589
TI - Isotope effects in the infrared spectra of OCS-He complexes and clusters.
AB - Infrared spectra of the OCS-He van der Waals complex and of OCS-He(N) clusters
have been studied in the region of the OCS nu1 fundamental band using a tunable
diode laser to probe a pulsed supersonic slit jet. For the complex, the spectrum
of the normal isotope, 16O12C32S-4He, has been considerably extended and the 34S-
and 13C-substituted forms have been recorded for the first time. The data could
be analyzed satisfactorily using a conventional asymmetric rotor Hamiltonian with
sextic centrifugal distortion terms. For the clusters, the 34S- and 13C
substituted forms have been observed and assigned for N = 2-7, including some
transitions with higher J values than previously reported for the normal isotope,
e.g., R5. The observed vibrational shifts, relative to the free OCS molecule,
were very similar to those of the normal isotope, and most of the difference
could be explained by simple scaling. These results constitute a subtle and
precise probe of intermolecular forces and dynamical effects in a system which is
of current interest for cluster studies.
PMID- 17042590
TI - Electron hydration dynamics in water clusters: A direct ab initio molecular
dynamics approach.
AB - Electron attachment dynamics of excess electron in water cluster (H2O)n (n = 2
and 3) have been investigated by means of full-dimensional direct ab initio
molecular dynamics (MD) method at the MP26-311++G(d,p) level. It was found that
the hydrogen bond breaking due to the excess electron is an important process in
the first stage of electron capture in water trimer. Time scale of electron
localization and hydrogen bond breaking were determined by the direct ab initio
MD simulation. The initial process of hydration in water cluster is clearly
visualized in the present study. In n = 3, an excess electron is first trapped
around the cyclic water trimer with a triangular form, where the excess electron
is equivalently distributed on the three water molecules at time zero. After 50
fs, the excess electron is concentrated into two water molecules, while the
potential energy of the system decreases by -1.5 kcal/mol from the vertical
point. After 100 fs, the excess electron is localized in one of the water
molecules and the potential energy decreases by -5.3 kcal/mol, but the triangular
form still remained. After that, one of the hydrogen bonds in the triangular form
is gradually broken by the excess electron, while the structure becomes linear at
100-300 fs after electron capture. The time scale of hydrogen bond breaking due
to the excess electron is calculated to be about 300 fs. Finally, a dipole bound
state is formed by the linear form of three water molecules. In the case of n =
2, the dipole bound anion is formed directly. The mechanism of electron hydration
dynamics was discussed on the basis of theoretical results.
PMID- 17042591
TI - First-principles study of intermediate size silver clusters: Shape evolution and
its impact on cluster properties.
AB - Low-energy isomers of Ag(N) clusters are studied within gradient-corrected
density functional theory over the size range of N = 9-20. The candidate
conformations are drawn from an extensive structural database created in a recent
exploration of Cu(N) clusters [M. Yang et al., J. Chem. Phys. 124, 24308 (2006)].
Layered configurations dominate the list of the lowest-energy isomers of Ag(N)
for N < 16. The most stable structures for N > 16 are compact with quasispherical
shapes. The size-driven shape evolution is similar to that found earlier for
Na(N) and Cu(N). The shape change has a pronounced effect on the cluster cohesive
energies, ionization potentials, and polarizabilities. The properties computed
for the most stable isomers of Ag(N) are in good agreement with the available
experimental data.
PMID- 17042592
TI - Theoretical investigation on 1H and 13C NMR chemical shifts of small alkanes and
chloroalkanes.
AB - Using density functional theory (DFT) with the B3LYP, PBE, and PBE0 exchange
correlation functionals as well as the Moller-Plesset second-order perturbation
theory (MP2) combined with a series of rather extended basis sets, 1H and 13C
chemical shifts of small alkanes and chloroalkanes (with different numbers of
chlorine atoms on specific positions) have been simulated and compared to
experimental data. For the 1H chemical shifts, theory tends to reproduce
experiment within the limits of the experimental errors. In the case of 13C
chemical shift, the differences between theory and experiment increase
monotonically with the number of chlorine atoms and exhibit a deviation from
additivity. This behavior is related to the saturation of the experimental 13C
chemical shifts with the number of chlorine atoms, whereas the evolution is
mostly linear at both DFT and MP2 levels of approximation. This difference has
been traced back to the relativistic spin-orbit coupling effects, which are
exalted as a result of the enhancement of the s character of the C atom when
increasing the number of linked Cl atoms. Thus, it was demonstrated that not only
electron correlation but also relativistic effects have to be considered for
estimating the 13C chemical shifts when several Cl atoms are directly attached to
the C atom. Linear (theory/experiment) regressions have then been performed for
the different types of C atoms, i.e., bearing one, two, and three Cl atoms, with
excellent correlation coefficients. The linear correlation relationships so
obtained can then serve to predict and facilitate the interpretation of the
nuclear magnetic resonance spectra of more complex compounds. Furthermore, by
investigating the basis set effects, the correlation between the chemical shifts
calculated using the 6-311 + G(2d,p) basis set and the more extended 6-311 +
G(2df,p) and aug-cc-pvtz basis sets is excellent, demonstrating that the choice
of the 6-311 + G(2d,p) basis set for calculating the 1H and 13C chemical shifts
is relevant.
PMID- 17042593
TI - Rotational spectrum of cyanoacetylene solvated with helium atoms.
AB - The high resolution microwave spectra of He(N)-HCCCN clusters were studied in the
size ranges of 1-18 and 25-31. In the absence of an accompanying infrared study,
rotational excitation energies were computed by the reptation quantum Monte Carlo
method and used to facilitate the search and assignment of R(0) transitions from
N > 6, as well as R(1) transitions with N > 1. The assignments in the range of 25
31 are accurate to +/-2 cluster size units, with an essentially certain relative
ordering. The rotational transition frequencies decrease with N = 1-6 and then
show oscillatory behavior for larger cluster sizes, which is now recognized to be
a manifestation of the onset and microscopic evolution of superfluidity. For
cluster sizes beyond completion of the first solvation shell the rotational
frequencies increase significantly above the large-droplet limit. This behavior,
common to other linear molecules whose interaction with He features a strong
nearly equatorial minimum, is analyzed using path integral Monte Carlo
simulations. The He density in the incipient second solvation shell is shown to
open a new channel for long permutation cycles, thus increasing the decoupling of
the quantum solvent from the rotation of the dopant molecule.
PMID- 17042594
TI - Jet cooled spectroscopy of H2DO+: Barrier heights and isotope-dependent tunneling
dynamics from H3O+ to D3O+.
AB - The first high resolution spectroscopic data for jet cooled H2DO+ are reported,
specifically via infrared laser direct absorption in the OH stretching region
with a slit supersonic jet discharge source. Transitions sampling upper (0-) and
lower (0+) tunneling states for both symmetric (nu1+ <-- 0+, nu1- <-- 0-, and nu1
<-- 0+) and antisymmetric (nu3+ <-- 0+ and nu3- <-- 0-) OH stretching bands are
observed, where +/- refers to wave function reflection symmetry with respect to
the planar umbrella mode transition state. The spectra can be well fitted to a
Watson asymmetric top Hamiltonian, revealing band origins and rotational
constants for benchmark comparison with high-level ab initio theory. Of
particular importance are detection and assignment of the relatively weak band
(nu1- <-- 0+) that crosses the inversion tunneling gap, which is optically
forbidden in H3O+ or D3O+, but weakly allowed in H2DO+ by lowering of the
tunneling transition state symmetry from D(3h) to C(2v). In conjunction with
other H2DO+ bands, this permits determination of the tunneling splittings to
within spectroscopic precision for each of the ground [40.518(10) cm(-1)], nu1 =
1 [32.666(6) cm(-1)], and nu3 = 1 [25.399(11) cm(-1)] states. A one-dimensional
zero-point energy corrected potential along the tunneling coordinate is
constructed from high-level ab initio CCSD(T) calculations (AVnZ, n = 3,4,5) and
extrapolated to the complete basis set limit to extract tunneling splittings via
a vibrationally adiabatic treatment. Perturbative scaling of the potential to
match splittings for all four isotopomers permits an experimental estimate of
DeltaV0 = 652.9(6) cm(-1) for the tunneling barrier, in good agreement with full
six-dimensional ab initio results of Rajamaki, Miani, and Halonen (RMH) [J. Chem.
Phys. 118, 10929 (2003)]. (DeltaV0 (RMH) = 650 cm(-1)). The 30%-50% decrease in
tunneling splitting observed upon nu1 and nu3 vibrational excitations arises from
an increase in OH stretch frequencies at the planar transition state,
highlighting the transition between sp2 and sp3 hybridizations of the OHD bonds
as a function of inversion bending angle.
PMID- 17042595
TI - Photodissociation of 1-bromo-2-butene, 4-bromo-1-butene, and cyclopropylmethyl
bromide at 234 nm studied using velocity map imaging.
AB - We present photofragment imaging experiments to characterize potential photolytic
precursors of three C4H7 radical isomers: 1-methylallyl, cyclopropylmethyl, and 3
buten-1-yl radicals. The experiments use 2+1 resonance enhanced multiphoton
ionization (REMPI) with velocity map imaging to state-selectively detect the
Br(2P(3/2)) and Br(2P(1/2)) atoms as a function of their recoil velocity imparted
upon photodissociation of 1-bromo-2-butene, cyclopropylmethyl bromide, and 4
bromo-1-butene at 234 nm as well as the angular distributions of the
photofragments. Energy and momentum conservation allows the internal energy
distribution of the nascent momentum-matched radicals to be derived. The radicals
are detected with single photon photoionization at 157 nm. In the case of the 1
methylallyl radical the photoionization cross section is expected to be
independent of internal energy in the range of 7-30 kcal/mol. Thus, comparison of
the product recoil kinetic energy distribution derived from the measurement of
the 1-methylallyl velocity distribution, detecting the radicals with 157 nm
photoionization, with a linear combination of the Br atom recoil kinetic energy
distributions allows us to derive reliable REMPI line strength ratios for the
detection of Br atoms and to test the assumption that the photoionization cross
section does not strongly depend on the internal energy of the radical. This line
strength ratio is then used to determine the branching to the Br(2P(3/2)) and
Br(2P(1/2)) product channels for the other two photolytic systems and to
determine the internal energy distribution of their momentum-matched radicals.
(We also revisit earlier work on the photodissociation of cyclobutyl bromide
which detected the Br atoms and momentum-matched cyclobutyl radicals.) This
allows us to test whether the 157 nm photoionization of these radicals is
insensitive to internal energy for the distribution of total internal
(vibrational+rotational) energy produced. We find that 157 nm photoionization of
cyclopropylmethyl radicals is relatively insensitive to internal energy, while 3
buten-1-yl radicals show a photoionization cross section that is markedly
dependent on internal energy with the lowest internal energy radicals not
efficiently detected by photoionization at 157 nm. We present electronic
structure calculations of the radicals and their cations to understand the
experimental results.
PMID- 17042596
TI - The lowest singlet-triplet excitation energy of BN: A converged coupled cluster
perspective.
AB - The notoriously small X 3Pi-a 1Sigma+ excitation energy of the BN diatomic has
been calculated using high-order coupled cluster methods. Convergence has been
established in both the one-particle basis set and the coupled cluster expansion.
Explicit inclusion of connected quadruple excitations T4 is required for even
semiquantitative agreement with the limit value, while connected quintuple
excitations T5 still have an effect of about 60 cm(-1). Still higher excitations
only account for about 10 cm(-1). Inclusion of inner-shell correlation further
reduces Te by about 60 cm(-1) at the CCSDT, and 85 cm(-1) at the CCSDTQ level.
Our best estimate, Te = 183+/-40 cm(-1), is in excellent agreement with earlier
calculations and experiment, albeit with a smaller (and conservative)
uncertainty. The dissociation energy of BN(X 3Pi) is De = 105.74+/-0.16 kcal/mol
and D0 = 103.57+/-0.16 kcal/mol.
PMID- 17042597
TI - Coupled-cluster studies of the electronic excitation spectra of silanes.
AB - The electronic excitation spectra of unsubstituted linear silanes (n
Si(m)H(2m+2), m = 1-6), cyclopentasilane (c-Si5H10), and neopentasilane (neo
Si5H12) have been studied at the coupled-cluster approximate singles and doubles
(CC2) level using Dunning's quadruple-zeta basis sets augmented with diffuse
functions (aug-cc-pVQZ). Comparisons with measured ultraviolet spectra for Si2H6
and n-Si3H8 show that CC2 calculations using these basis sets yield excitation
energies in good agreement with experiment. The calculated excitation thresholds
for Si2H6 and n-Si3H8 of 7.61 and 6.68 eV are only 0.05 eV larger than the gas
phase values of 7.56 and 6.63 eV, respectively. For n-Si4H10, n-Si5H12, and neo
Si5H12, the calculated excitation thresholds of 6.51, 6.14, and 6.87 eV for the
lowest dipole-allowed transitions are about 0.4 eV larger than the corresponding
liquid-phase data of 6.05, 5.77, and 6.53 eV; the discrepancy can mainly be
attributed to solvent effects. The obtained excitation thresholds for n-Si6H14 is
5.85 eV, whereas no experimental data are available for its optical gap.
Calculations using the Karlsruhe triple-zeta valence basis sets augmented with
single and double sets of polarization functions show that very large basis sets
augmented with diffuse functions are needed for obtaining accurate excitation
energies. The optical gaps for silanes obtained using the triple-zeta
polarization basis sets were found to be 0.4 and 0.2 eV larger than those
obtained using Dunning's quadruple-zeta basis sets. Excitation thresholds
calculated at density functional theory levels using generalized gradient
approximation are 0.7-1.0 eV smaller than the experimental values and by
employing hybrid functionals they are 0.3-0.4 eV below the experimental
thresholds. By adding the present basis-set correction and environmental effects
to the previously calculated CC2 value for the excitation threshold of the
Si29H36 silicon nanocluster, the extrapolated absorption threshold is 4.0 eV as
compared to the recently reported experimental value of 3.7 eV.
PMID- 17042598
TI - Photodissociation dynamics of vinyl fluoride (CH2CHF) at 157 and 193 nm:
Distributions of kinetic energy and branching ratios.
AB - Using photofragment translational spectroscopy and tunable vacuum-ultraviolet
ionization, we measured the time-of-flight spectra of fragments upon
photodissociation of vinyl fluoride (CH2CHF) at 157 and 193 nm. Four primary
dissociation pathways--elimination of atomic F, atomic H, molecular HF, and
molecular H2--are identified at 157 nm. Dissociation to C2H3 + F is first
observed in the present work. Decomposition of internally hot C2H3 and C2H2F
occurs spontaneously. The barrier heights of CH2CH --> CHCH + H and cis-CHCHF -->
CHCH + F are evaluated to be 40+/-2 and 44+/-2 kcal mol(-1), respectively. The
photoionization yield spectra indicate that the C2H3 and C2H2F radicals have
ionization energies of 8.4+/-0.1 and 8.8+/-0.1 eV, respectively. Universal
detection of photoproducts allowed us to determine the total branching ratios,
distributions of kinetic energy, average kinetic energies, and fractions of
translational energy release for all dissociation pathways of vinyl fluoride. In
contrast, on optical excitation at 193 nm the C2H2 + HF channel dominates whereas
the C2H3 + F channel is inactive. This reaction C2H3F --> C2H2 + HF occurs on the
ground surface of potential energy after excitation at both wavelengths of 193
and 157 nm, indicating that internal conversion from the photoexcited state to
the electronic ground state of vinyl fluoride is efficient. We computed the
electronic energies of products and the ionization energies of fluorovinyl
radicals.
PMID- 17042599
TI - Microscopic simulations of molecular cluster decay: Does the carrier gas affect
evaporation?
AB - We develop a kinetic theory of cluster decay by considering the stochastic motion
of molecules within an effective potential of mean force (PMF) due to the
cluster. We perform molecular dynamics simulations on a 50-atom argon cluster to
determine the mean radial force on a component atom and hence the confining
potential of mean force. Comparisons between isolated clusters and clusters
thermostatted through the presence of a 100-atom helium carrier gas show that the
heat bath has only a slight effect upon the PMF. This confirms the validity of
calculations of cluster properties using isolated cluster simulations. The PMF is
used to calculate the atomic evaporation rate from these clusters, and results
are compared with the predictions of the capillarity approximation together with
detailed balance, both components of the classical theory of aerosol nucleation.
PMID- 17042600
TI - Counterpoise corrected geometries of hydrated complexes.
AB - We have calculated the equilibrium geometries of the hydrated complexes, H2O.CO2,
H2O.CS2,H2O.OCS, H2O.SO2, and H2O.SO3, in the electronic ground state. We have
used the coupled cluster with singles, doubles, and perturbative triples ab
initio method with a correlation consistent augmented triple-zeta basis set. We
find that a counterpoise corrected optimization scheme is important for an
accurate description of the geometries. These high level ab initio calculated
geometries are of comparable quality to those obtained experimentally.
PMID- 17042601
TI - S(1D2) atomic orbital polarization in the photodissociation of OCS at 193 nm:
Construction of the complete density matrix.
AB - The absolute velocity-dependent alignment and orientation for S(1D2) atoms from
the photodissociation of OCS at 193 nm were measured using the dc slice imaging
method. Three main peaks ascribed to specific groups of high rotational levels of
CO in the vibrational ground state were found, with rotationally resolved rings
in a fourth slow region ascribed to weak signals associated with excited
vibrational states of CO. The observed speed-dependent beta and polarization
parameters support the interpretation that there are two main dissociation
processes: a simultaneous two-surface (A' and A") excitation and the initial
single-surface (A') excitation followed by the nonadiabatic crossing to ground
state. At 193 nm photodissociation, the nonadiabatic dissociation process is
strongly enhanced relative to longer wavelengths. The angle- and speed-dependent
S(1D2) density matrix can be constructed including the higher order (K = 3,4)
contributions for the circularly polarized dissociation light. This was
explicitly done for selected energies and angles. It was found in one case that
the density matrix is sensitively affected by the rank 4 terms, suggesting that
the higher order contributions should not be overlooked for an accurate picture
of the dissociation dynamics in this system.
PMID- 17042602
TI - Electronic spectroscopy of NO-(Rg)x complexes (Rg = Ne,Ar) via the 4s and 3d
Rydberg states.
AB - We have employed (2 + 1) resonance enhanced multiphoton ionization spectroscopy
to investigate the 3d and 4s Rydberg states of the NO molecule when bound to the
surface of Rg(x) clusters (Rg = rare gas). We observe that the spectra of the NO
Ar(x) species converge in appearance as x increases, and this is discussed in
terms of two Rg atoms interacting with the NO+ core, with other Rg atoms being
"outside" the Rydberg orbital. We show that the interaction of each of the Rg
atoms with the NO is essentially independent for the NO-Rg2 complexes: both by
comparing our spectra for Rydberg states of NO-Rg and NO-Rg2, and from the
results of ab initio calculations on NO+ - Rg and NO+ - Rg2. In addition, we
discuss the disappearance of some electronic bands upon complexation in terms of
Franck-Condon factors that are very sensitive to the angular coordinate. We
relate our results to those of the bulk by comparing to the previously reported
electronic spectroscopy of NO in both Rg matrices and He nanodroplets.
PMID- 17042603
TI - Size effects in the infrared spectra of NH3 ice nanoparticles studied by a
combined molecular dynamics and vibrational exciton approach.
AB - Infrared extinction spectra of ammonia ice nanoparticles with radii between 2 and
10 nm show pronounced band shape variations depending on the conditions of
particle formation by collisional cooling. We present experimental and
theoretical evidence showing that the variations in the region of the nu2
(umbrella) fundamental are due to changes in the particle size. The effect is
analyzed in terms of an explicit atomistic model of the particles' structure and
vibrational dynamics. An explicit potential function combined with a novel
extension of the vibrational exciton approach allows us to simulate extinction
spectra for particles containing up to 16,000 atoms. It is shown that the
particles formed under the conditions of our experiments consist of a crystalline
core surrounded by an amorphous shell with an approximately constant thickness of
1-2 nm. For the nu2 fundamental, this shell gives rise to a broad band [full
width at half maximum (FWHM) 72 cm(-1)] blueshifted by about 19 cm(-1) relative
to a narrow peak (FWHM of 19 cm(-1)) which arises from the crystalline core.
PMID- 17042604
TI - Effect of donor-acceptor interaction strength on excitation energy migration and
diffusion at high donor concentrations.
AB - The migration and diffusion modulated excitation energy transfer has been studied
in a new dye pair 7-diethylamino-4-methylcoumarin (donor) to 3,3'
dimethyloxacarbocyanine iodide (acceptor) by steady-state and picosecond time
resolved spectroscopy. To reduce the artifact of self-absorption, at high donor
concentrations, the time-resolved studies have been carried out in thin films of
polyvinyl alcohol (solid matrix) and in methanol (liquid phase) at front-face
geometry of excitation. The Forster-type (nonradiative) energy transfer [Discuss.
Faraday Soc. 27, 7 (1959)] takes place directly from donor to acceptor in case of
solid matrix, while Yokota-Tanimoto model [J. Phys. Soc. Jpn. 22, 779 (1967)] for
diffusion has been found to be operating in the liquid phase. It has been found
here that the high interaction strength between donor and acceptor molecules as
compared to that among donors masks the effect of energy migration and diffusion
at high donor concentrations. The rate and efficiency of energy transfer increase
with increasing the acceptor concentration. This has been confirmed by the study
of acceptor kinetics.
PMID- 17042605
TI - Supercooling of aqueous NaCl and KCl solutions under acoustic levitation.
AB - The supercooling capability of aqueous NaCl and KCl solutions is investigated at
containerless state by using acoustic levitation method. The supercooling of
water is obviously enhanced by the alkali metal ions and increases linearly with
the augmentation of concentrations. Furthermore, the supercooling depends on the
nature of ions and is 2-3 K larger for NaCl solution than that for KCl solution
in the present concentration range: Molecular dynamics simulations are performed
to reveal the intrinsic correlation between supercoolability and microstructure.
The translational and orientational order parameters are applied to
quantitatively demonstrate the effect of ionic concentration on the hydrogen-bond
network and ice melting point. The disrupted hydrogen-bond structure determines
essentially the concentration dependence of supercooling. On the other hand, the
introduced acoustic pressure suppresses the increase of supercooling by promoting
the growth and coalescence of microbubbles, the effective nucleation catalysts,
in water. However, the dissolved ions can weaken this effect, and moreover the
degree varies with the ion type. This results in the different supercoolability
for NaCl and KCl solutions under the acoustic levitation conditions.
PMID- 17042606
TI - Theoretical direct correlation function for two-dimensional fluids of
monodisperse hard spheres.
AB - The direct correlation function plays an important role in describing the effects
of the structure of particle systems with respect to light diffraction, x-ray
diffraction as well as transmission and transmission fluctuations of radiation
through a dense suspension. In this paper, the direct correlation function for a
monolayer of monodisperse hard spheres or disks is derived theoretically. Based
on the approximation of Baus and Colot [Phys. Rev. A 36, 3912 (1987)] and the
equation of state for a fluid of hard disks by Santos et al. [J. Chem. Phys. 103,
4622 (1995)], we propose a new direct correlation function, which compares well
to the approximate analytical expressions and gives a good prediction of the
structure factor in a wide range of monolayer density or suspension
concentration. The resulting radial distribution function also agrees well with
Monte Carlo computer simulation data. The corresponding contact values of the
radial distribution function compare well with the results of analytic
approximations, numerical solutions, and computer simulations. Our proposed
direct correlation function is applied to the transmission fluctuation
spectrometric study. Experimental results show good agreement with the theory.
PMID- 17042607
TI - Scaling fields and pressure mixing in the Widom-Rowlinson model.
AB - We address the issues of scaling fields and of pressure mixing in the penetrable
sphere model. This model has an exact symmetry locus from which analytical
results may be derived. Based on exact results, we demonstrate that the scaling
fields are analytic functions of temperature and chemical potential only. We
conclude that there is no pressure mixing in this model. Our findings are in
accord with numerical simulations for the same model.
PMID- 17042608
TI - Expressions for the stress and elasticity tensors for angle-dependent potentials.
AB - The stress and elasticity tensors for interatomic potentials that depend
explicitly on bond bending and dihedral angles are derived by taking strain
derivatives of the free energy. The resulting expressions can be used in Monte
Carlo and molecular dynamics simulations in the canonical and microcanonical
ensembles. These expressions are particularly useful at low temperatures where it
is difficult to obtain results using the fluctuation formula of Parrinello and
Rahman [J. Chem. Phys. 76, 2662 (1982)]. Local elastic constants within
heterogeneous and composite materials can also be calculated as a function of
temperature using this method. As an example, the stress and elasticity tensors
are derived for the second-generation reactive empirical bond-order potential.
This potential energy function was used because it has been used extensively in
computer simulations of hydrocarbon materials, including carbon nanotubes, and
because it is one of the few potential energy functions that can model chemical
reactions. To validate the accuracy of the derived expressions, the elastic
constants for diamond and graphite and the Young's Modulus of a (10,10) single
wall carbon nanotube are all calculated at T = 0 K using this potential and
compared with previously published data and results obtained using other
potentials.
PMID- 17042609
TI - Changes of relaxation dynamics of a hydrogen-bonded glass former after removal of
the hydrogen bonds.
AB - Dielectric relaxation spectra of two closely related glass formers, dipropylene
glycol [H-(C3H6O)2-OH] and dipropylene glycol dimethyl ether [CH3-O-(C3H6O)2
CH3], were measured at ambient and elevated pressures in the supercooled and the
glassy states are presented. Hydrogen bonds formed in dipropylene glycol are
removed when its ends are replaced by two methyl groups to become dipropylene
glycol dimethyl ether. In the process, the primary relaxation, the excess wing,
and the resolved secondary relaxation of dipropylene glycol are all modified when
the structure is transformed to become dipropylene glycol dimethyl ether. The
modifications include the pressure and temperature dependences of these
relaxation processes and their interrelations. Thus, by comparing the dielectric
spectra of these two closely related glass formers at ambient and elevated
pressures, the differences in the relaxation dynamics and properties in the
presence and absence of hydrogen bonding are identified.
PMID- 17042610
TI - Origins of linewidth in 1H magic-angle spinning NMR.
AB - A detailed study of the factors determining the linewidth (and hence resolution)
in 1H solid-state magic-angle spinning NMR is described. Although it has been
known from the early days of magic-angle spinning (MAS) that resolution of
spectra from abundant nuclear spins, such as 1H, increases approximately linearly
with increasing sample rotation rate, the difficulty of describing the dynamics
of extended networks of coupled spins has made it difficult to predict a priori
the resolution expected for a given sample. Using recently developed, highly
efficient methods of numerical simulation, together with experimental
measurements on a variety of test systems, we propose a comprehensive picture of
1H resolution under MAS. The "homogeneous" component of the linewidth is shown to
depend primarily on the ratio between an effective local coupling strength and
the spin rate, modified by geometrical factors which loosely correspond to the
"dimensionality" of the coupling network. The remaining "inhomogeneous" component
of the natural linewidth is confirmed to have the same properties as in dilute
spin NMR. Variations in the NMR frequency due to chemical shift effects are shown
to have minimal impact on 1H resolution. The implications of these results for
solid-state NMR experiments involving 1H and other abundant-spin nuclei are
discussed.
PMID- 17042611
TI - Relationships between three-body and two-body interactions in fluids and solids.
AB - Molecular dynamics data are reported for two-body and three-body interactions in
noble gases at densities covering the gas, liquid, and solid phases. The data
indicate that simple relationships exist between three- and two-body interactions
in both fluid and solid phases. The relationship for liquids has a simple density
dependence with only one external parameter. In contrast, the solid phase
relationship depends both on density and on the square of density and requires
the evaluation of two parameters. The relationships are tested for both system
size and temperature dependences. The values of the relationship parameters are
only sensitive to system size when a small number of atoms are involved. For 500
or more atoms, they remain nearly constant. The relationships are valid for both
subcritical and slightly supercritical temperatures. A practical benefit of the
relationships is that they enable the use of two-body intermolecular potentials
for the prediction of the properties of real systems without the computational
expense of three-body calculations.
PMID- 17042612
TI - Neutron powder diffraction studies of sulfuric acid hydrates. I. The structure of
sulfuric acid hemitriskaidekahydrate D2SO4.6(1/2)D2O.
AB - We report the first neutron diffraction data from D2SO4.6(1/2)D2O. The crystal is
monoclinic, space group Cm, with four formula units per unit cell. At 4.2 K the
unit cell dimensions are a = 6.253 26(4) A, b = 26.813 62(10) A, c = 5.908 45(2)
A, and beta = 112.1939(3) degrees [V = 917.286(6) A3 and rho(deuterated) =
1664.14(2) kg m(-3)]. The deuteron positions refined from the neutron data are in
agreement with those established by single crystal x-ray analysis [D. Mootz and
A. Merschenz-Quack, Z. Naturforsch. B 42, 1231 (1987)], but not with those found
from the ab initio simulation of Hirsch and Ojamae [Acta Crystallogr, Sect. B:
Struct. Sci. 60, 179 (2004)]. The crystal consists of SO4(2-), D3O+ ions, and D2O
molecules hydrogen bonded to form a layered structure in which sheets of
"icelike" D3O+ and D2O are separated by layers of opposing SO4(2-) tetrahedra.
PMID- 17042613
TI - Competition between ultrafast relaxation and photoionization in excited
prefluorescent states of tryptophan and indole.
AB - The quantum yield of photoionization of TrpH and IndH from the nonrelaxed
prefluorescent state S* increases with the temperature decrease. This effect is
attributed to the competition between temperature independent ionization and
ultrafast thermal relaxation S* --> S1. The rate constant of the relaxation does
not depend on the solvent and on the presence of the amino acid side chain: the
temperature dependences of photoionization quantum yield, obtained for TrpH and
IndH in different solvents, practically coincide. The activation energy for the
relaxation rate constant Er approximately 4.5 kJ/mol probably corresponds to
intramolecular process or to the formation of the vibronically excited transient
complex between photoexcited molecule and solvent molecules.
PMID- 17042614
TI - Orientational dynamics of isotopically diluted H2O and D2O.
AB - We use femtosecond midinfrared pump-probe spectroscopy to compare the ultrafast
dynamics of HDO dissolved in D2O and H2O. For both systems the vibrational energy
relaxation proceeds through an intermediate state. The relaxation leads to
heating of the sample, which is observed in the transient spectra. In order to
obtain the correct anisotropy decay, the ingrowing heating signal is subtracted
from the raw data. For the OD vibration this procedure works well. For the OH
vibration, however, we find an additional effect that leads to a severe
distortion of the anisotropy. We show that this effect can be explained by a
slightly faster reorientation of excited molecules during their relaxation as
compared to unexcited molecules. We construct a model that includes this effect
and is able to reproduce the experimental data. Using this model we show how the
distorted anisotropy can be corrected.
PMID- 17042615
TI - Dynamical properties of the soft sticky dipole-quadrupole-octupole water model: a
molecular dynamics study.
AB - The dynamical properties of the soft sticky dipole-quadrupole-octupole (SSDQO)
water model using SPC/E moments are calculated utilizing molecular dynamics
simulations. This new potential for liquid water describes the water-water
interactions by a Lennard-Jones term and a sticky potential, which is an
approximate moment expansion with point dipole, quadrupole, and octupole moments,
and reproduces radial distribution functions of pure liquid water using the
moments of SPC/E [Ichiye and Tan, J. Chem. Phys. 124, 134504 (2006)]. The forces
and torques of SSDQO water for the dipole-quadrupole, quadrupole-quadrupole, and
dipole-octupole interactions are derived here. The simulations are carried out at
298 K in the microcanonical ensemble employing the Ewald method for the long
range dipole-dipole interactions. Here, various dynamical properties associated
with translational and rotational motions of SSDQO water using the moments of
SPC/E (SSDQO:SPC/E) water are compared with the results from SPC/E and also
experiment. The self-diffusion coefficient of SSDQO:SPC/E water is found to be in
excellent agreement with both SPC/E and experiment whereas the single particle
orientational relaxation time for dipole vector is better than SPC/E water but it
is somewhat smaller than experiment. The dielectric constant of SSDQO:SPC/E is
essentially identical to SPC/E, and both are slightly lower than experiment.
Also, molecular dynamics simulations of the SSDQO water model are found to be
about twice as fast as three-site models such as SPC/E.
PMID- 17042616
TI - Identification and properties of the 1La and 1Lb states of pyranine.
AB - The spectroscopic locations of the 1La and 1Lb electronic states of pyranine (1
hydroxy-3,6,8-pyrenetrisulfonic acid, commonly referred to as HPTS), as well as
several related compounds, are found using magnetic circular dichroism
spectroscopy as well as absorption and fluorescence spectroscopies. These
electronic states have been discussed in connection with the photoacid properties
of HPTS. Polarization selective fluorescence spectroscopy is used to identify the
transition dipole directions of the electronic states of the compounds studied.
The issue of the origin for the changes in vibronic structure of HPTS in
different solvents is addressed. It is demonstrated that a Brownian oscillator
model, in which the strength of the coupling of the electronic states to the
solvent changes with solvent, is sufficient to reproduce the trends in the shapes
of the vibronic structure.
PMID- 17042617
TI - Homogeneous nucleation at high supersaturation and heterogeneous nucleation on
microscopic wettable particles: A hybrid thermodynamic/density-functional theory.
AB - Homogeneous nucleation at high supersaturation of vapor and heterogeneous
nucleation on microscopic wettable particles are studied on the basis of Lennard
Jones model system. A hybrid classical thermodynamics and density-functional
theory (DFT) approach is undertaken to treat the nucleation problems. Local
density approximation and weighted-density approximation are employed within the
framework of DFT. Special attention is given to the disjoining pressure of small
liquid droplets, which is dependent on the thickness of wetting film and radius
of the wettable particle. Different contributions to the disjoining pressure are
examined using both analytical estimations and numerical DFT calculation. It is
shown that van der Waals interaction results in negative contribution to the
disjoining pressure. The presence of wettable particles results in positive
contribution to the disjoining pressure, which plays the key role in the
heterogeneous nucleation. Several definitions of the surface tension of liquid
droplets are discussed. Curvature dependence of the surface tension of small
liquid droplets is computed. The important characteristics of nucleation,
including the formation free energy of the droplet and nucleation barrier height,
are obtained.
PMID- 17042618
TI - A mechanical representation of entropy for a large finite system.
AB - The temporal evolution of the entropy of a mechanical system as described by a
single trajectory is computed using the Clausius [Philos. Mag. 40, 122 (1868)]
equality. This requires computing the maximal work that can be done by the system
and comparing it to the actual work performed. A single trajectory suffices to
determine the entropy when it is "typical," meaning that average values of
mechanical variables will not be different when computed using trajectories with
different initial conditions. The results are illustrated for small rare gas
clusters heated and compressed by an impact at a hard surface.
PMID- 17042619
TI - Dielectric study on the flow alignment in 4-n-pentyl-4'-cyanobiphenyl.
AB - Dielectric permittivity and loss are measured under steady shear flow as
functions of temperature, shear rate, electric field frequency, and electric
field strength in the nematic (N) and the isotropic (I) phases of 4-n-pentyl-4'
cyanobiphenyl. In the N phase, the dielectric permittivity in the quiescent state
is largely modified if the steady shear flow is applied. These behaviors are
discussed based on the Leslie-Ericksen theory [Q. J. Mech. Appl. Math. 19, 357
(1966); Arch. Ration. Mech. Anal. 4, 231 (1960)], showing that the dielectric
properties under the shear flow are consistently interpreted in terms of the flow
alignment of the director, a unit vector specifying the orientation of the liquid
crystals. It is also suggested that the behaviors of dielectric permittivities
are similar to those of the viscosities.
PMID- 17042620
TI - Improvement on macroscopic compressibility approximation and beyond.
AB - A numerical procedure is proposed to extend the thermodynamic perturbation
expansion (TPE) to a higher order. It is shown that the present second order term
is superior to that due to a macroscopic compressibility approximation (MCA), a
local compressibility approximation, and a superposition approximation by Barker
and Henderson [Rev. Mod. Phys. 48, 587 (1976)]. Extensive model calculation and
comparison with simulation data available in literature and supplied in the
present report indicate that the present third order TPE is superior to a
previous second order TPE based on the MCA, two previous perturbation theories,
which are respectively based on an analytical mean spherical approximation for an
Ornstein-Zernike equation, and an assumed explicit functional form for the
Laplace transform of radial distribution function multiplied by radial distance,
and a recent generalized van der Waals theory. The present critical temperature
for a hard core attractive Yukawa fluid of varying range is in very good
agreement with that due to a hierarchical reference theory. The present third
order TPE is computationally far more modest than the self-consistent integral
equation theory, and therefore is a viable alternative to use of the latter.
PMID- 17042621
TI - Hydrogen bonding and induced dipole moments in water: predictions from the
Gaussian charge polarizable model and Car-Parrinello molecular dynamics.
AB - We compare a new classical water model, which features Gaussian charges and
polarizability (GCPM) with ab initio Car-Parrinello molecular dynamics (CPMD)
simulations. We compare the total dipole moment, the total dipole moment
distribution, and degree of hydrogen bonding at ambient to supercritical
conditions. We also compared the total dipole moment calculated from both the
electron density (partitioning the electron density among molecules based on a
zero electron flux condition), and from the center of localized Wannier function
centers (WFCs). Compared to CPMD, we found that GCPM overpredicts the dipole
moment derived by partitioning the electron density and underpredicts that
obtained from the WFCs, but exhibits similar trends and distribution of values.
We also found that GCPM predicted similar degrees of hydrogen bonding compared to
CPMD and has a similar structure.
PMID- 17042622
TI - Water mediated attraction between repulsive ions: a cluster-based simulation
approach.
AB - Could two like ions be attractive to each other in the presence of water? To
address this question and to further interrogate the intriguing solvent effects
at a molecular level on multiply charged species, a "bottom-up" simulation
approach was formulated, from which the inter-ionic potential of mean force and
other properties were monitored closely with the gradual addition of the water
molecules. This approach was first tested on a commonly studied ion pair (namely,
Na+ and Cl-), where excellent agreement with the published bulk-phase data was
found. Further application of this approach to the like-ion pair indicated that
an attractive interaction between two anions or two cations can be induced by the
addition of an appropriate number of water molecules. This result corroborates a
recent experimental report of an intriguing folding of a dianionic polymer into a
more compact structure with the addition of water molecules in gas phase as well
as previous theoretical findings of possible attraction between like-ion pairs in
bulk aqueous phases.
PMID- 17042623
TI - Detection of multiple-quantum coherences with projective nuclear magnetic
resonance measurement.
AB - It is shown that in nuclear magnetic resonance, multiple-quantum (MQ) coherences
can be detected "instantly" by exploiting the principle of quantum-mechanical
projective measurement. Therefore, the mixing period, which involves collective
multispin dynamics and converts MQ coherences into observable single-quantum
coherence (magnetization), is not necessary. The experimental examples are given
for two finite clusters: benzene in liquid crystal and liquid crystal 4'-n-pentyl
4-cyanobiphenyl, and for solid adamantane with an infinite network of dipolar
couplings.
PMID- 17042624
TI - Extended spin-boson model for nonadiabatic hydrogen tunneling in the condensed
phase.
AB - A nonadiabatic rate expression for hydrogen tunneling reactions in the condensed
phase is derived for a model system described by a modified spin-boson
Hamiltonian with a tunneling matrix element exponentially dependent on the
hydrogen donor-acceptor distance. In this model, the two-level system
representing the localized hydrogen vibrational states is linearly coupled to the
donor-acceptor vibrational mode and the harmonic bath. The Hamiltonian also
includes bilinear coupling between the donor-acceptor mode and the bath
oscillators. This coupling provides a mechanism for energy exchange between the
two-level system and the bath through the donor-acceptor mode, thereby
facilitating convergence of the time integral of the probability flux correlation
function for the case of weak coupling between the two-level system and the bath.
The dependence of the rate constant on the model parameters and the temperature
is analyzed in various regimes. Anomalous behavior of the rate constant is
observed in the weak solvation regime for model systems that lack an effective
mechanism for energy exchange between the two-level system and the bath. This
theoretical formulation is applicable to a wide range of chemical and biological
processes, including neutral hydrogen transfer reactions with small solvent
reorganization energies.
PMID- 17042625
TI - Hole localization in Al doped silica: A DFT + U description.
AB - Despite density functional theory (DFT) being the most widely used ab initio
approach for studying the properties of oxide materials, the modeling of
localized hole states in doped or defective oxides can be a challenge. The
electronic hole formed when silica is doped with aluminum is such a defect, for
which a DFT description of the atomic and electronic structures has previously
been found to be inconsistent with experiment, while Hartree-Fock provides a
consistent description. We have applied the DFT + U approach to this problem and
find that the structural distortions around the dopant are consistent with
experimental data as well as earlier cluster calculations using Hartree-Fock and
perturbation theory. A hole state is found 1.1 eV (1.6 eV experimentally) above
the top of the valence band with localization of spin on the oxygen atom which
shows the elongated Al-O distance. A formation energy of 5.7 eV is found. We
discuss implications for using DFT+U to model defective oxide systems with O 2p
holes.
PMID- 17042626
TI - Freezing of hard spheres confined in narrow cylindrical pores.
AB - Monte Carlo simulations for the equation of state and phase behavior of hard
spheres confined inside very narrow hard tubes are presented. For pores whose
radii are greater than 1.1 hard sphere diameters, a sudden change in the density
and the microscopic structure of the fluid is neatly observed, indicating the
onset of freezing. In the high-density structure the particles rearrange in such
a way that groups of three particles fit in sections across the pore.
PMID- 17042627
TI - Evidence of meniscus interface transport in dip-pen nanolithography: An annular
diffusion model.
AB - Ring shaped dots were patterned with mercaptohexadecanoic acid ink by dip-pen
nanolithography. These dots have an ink-free inner core surrounded by an inked
annular region, making them different from the filled dots usually obtained. This
suggests a different transport mechanism than the current hypothesis of bulk
water meniscus transport. A meniscus interface ink transport model is proposed,
and its general applicability is demonstrated by predicting the patterned dot
radii of chemically diverse inks.
PMID- 17042628
TI - Kinetics of droplet condensation through a double free-energy barrier.
AB - Results are presented for the kinetics of nucleation of liquid droplets from a
one-component vapor phase on a planar lyophobic substrate patterned with a large
number of easily wettable (lyophilic) circular domains. If the wettability of
these lyophilic domains is characterized by a contact angle smaller than pi2, for
intermediate values of the supersaturation, the condensation of a droplet on a
lyophilic domain occurs through a free-energy barrier with two maxima, that is,
through a double barrier. A simple model is proposed for the kinetics of droplet
condensation through a double barrier that combines Kramers's [Physica (Utrecht)
7, 284 (1940)] transition rate theory with known results of nucleation theory. In
the framework of this model, the solution is derived for the steady-state limit
of the nucleation process. The number of lyophilic domains available for droplet
condensation reduces with time as domains are occupied by droplets. The problem
of droplet condensation through a double barrier is solved taking into account
the effect of the time-dependent depletion in the number of available lyophilic
domains.
PMID- 17042629
TI - Low sticking probability in the nonactivated dissociation of N2 molecules on
W(110).
AB - The six-dimensional potential energy surface for the dissociation of N2 molecules
on the W(110) surface has been determined by density functional calculations and
interpolated using the corrugation reducing procedure. Examination of the
resulting six-dimensional potential energy surface shows that nonactivated paths
are available for dissociation. In spite of this, the dissociation probability
goes to a very small value when the impact energy goes to zero and increases with
increasing energy, a behavior usually associated with activated systems.
Statistics on the dynamics indicate that this unconventional result is a
consequence of the characteristics of the potential energy surface at long
distances. Furthermore, two distinct channels are identified in the dissociation
process, namely, a direct one and an indirect one. The former is responsible for
dissociation at high energies. The latter, which includes long-lasting dynamic
trapping in the vicinity of a potential well above the W top position, is the
leading mechanism at low and intermediate energies.
PMID- 17042630
TI - O2-coverage-dependent CO oxidation on reduced TiO2(110): A first principles
study.
AB - First principles periodic slab calculations based on gradient-corrected density
functional theory have been performed to investigate CO oxidation on rutile
TiO2(110) at varying O2 coverages (theta = 1, 2, and 3, where theta is defined as
the number of O2 per oxygen vacancy). For each coverage we only present the
reaction of CO with oxygen species in the most stable configuration. Our results
show a significant variation in the oxidation activation energy with O2 coverage.
PMID- 17042631
TI - Colloidal electroconvection in a thin horizontal cell. II. Bulk electroconvection
of water during parallel-plate electrolysis.
AB - We recently have reported [J. Chem. Phys. 122, 164701 (2005)] a family of
electroconvective patterns that arise when charge-stabilized colloidal
dispersions are driven by constant (dc) vertical electric fields. Competition
between gravity and electrokinetic forces acting on the individual spheres in
this system leads to the formation of highly organized convective instabilities
involving hundreds of spheres. Here, we report a distinct class of
electroconvective patterns that emerge in confined aqueous dispersions at higher
biases. These qualitatively resemble the honeycomb and labyrinthine patterns
formed during thermally driven Rayleigh-Benard convection, but arise from a
distinct mechanism. Unlike the localized colloidal electroconvective patterns
observed at lower biases, moreover, these system-spanning patterns form even
without dispersed colloidal particles. Rather, they appear to result from an
underlying electroconvective instability during electrolysis in the parallel
plate geometry. This contrasts with recent theoretical results suggesting that
simple electrolytes are linearly stable against electroconvection.
PMID- 17042632
TI - Hydrogen bonding in the LaNi3BH3 hydride.
AB - The electronic structure of the intermetallic LaNi3B as well as the novel hydride
LaNi3BH3 have been theoretically investigated by means of quantum chemistry
methods. We employed a mixed approach to investigate the electronic structure of
these compounds: state-of-the-art energy band calculations and molecular cluster
computations. We computed the energy bands and the total and partial density of
states using both the linear-augmented plane waves and projector-augmented wave
methods. In addition the electronic structure of three representative clusters of
the local environment of Ni atoms was investigated by quantum chemistry ab initio
molecular calculations. In this report, we discuss the chemical bonding and we
investigated the H site occupancy energies and correlate this estimate with the
occupancy fraction and metal-hydrogen distances experimentally observed.
PMID- 17042633
TI - Complete wetting of curved microscopic channels.
AB - We have measured the adsorption of argon films on arrays of microscopic nonlinear
cusps and of semicircular channels. In the former case, we observe a distinct
crossover from a planarlike to a geometry dependent growth behavior near liquid
vapor bulk coexistence, characterized by a growth exponent chi equal to -0.96+/
0.04 in very good agreement with the predictions of a recent scaling theory [C.
Rascon and A. O. Parry, J. Chem. Phys. 112, 5175 (2000)]. The crossover location
is also consistent with theory. Instead, on the concave channels we find a much
steeper growth near saturation that may signal the formation of two menisci at
both sides of the channel bottom.
PMID- 17042634
TI - Dynamical motions of lipids and a finite size effect in simulations of bilayers.
AB - Molecular dynamics (MD) simulations of dipalmitoylphosphatidylcholine bilayers
composed of 72 and 288 lipids are used to examine system size dependence on
dynamical properties associated with the particle mesh Ewald (PME) treatment of
electrostatic interactions. The lateral diffusion constant Dl is 2.92 x 10(-7)
and 0.95 x 10(-7) cm2/s for 72 and 288 lipids, respectively. This dramatic finite
size effect originates from the correlation length of lipid diffusion, which
extends to next-nearest neighbors in the 288 lipid system. Consequently,
diffusional events in smaller systems can propagate across the boundaries of the
periodic box. The internal dynamics of lipids calculated from the PME simulations
are independent of the system size. Specifically, reorientational correlation
functions for the slowly relaxing phosphorus-glycerol hydrogen, phosphorus
nitrogen vectors, and more rapidly relaxing CH vectors in the aliphatic chains
are equivalent for the 72 and 288 lipid simulations. A third MD simulation of a
bilayer with 72 lipids using spherical force-shift electrostatic cutoffs resulted
in interdigitated chains, thereby rendering this cutoff method inappropriate.
PMID- 17042635
TI - Interfacial structures of methanol:water mixtures at a hydrophobic interface
probed by sum-frequency vibrational spectroscopy.
AB - Sum-frequency vibrational spectroscopy was used to study interfacial structure of
methanol:water mixtures at an octyltrichlorosilane-covered hydrophobic surface.
Methanol was found to adsorb preferentially than water at the interface with its
methyl group tilted from the surface normal by approximately 35 degrees for all
methanol concentrations. Redshift of the methanol symmetric stretch mode, gradual
disappearance of the water dangling-OH mode, and blueshifts of the dangling and
liquidlike bonded-OH modes were also observed as the methanol concentration
increased. They could be understood from the change of the interfacial hydrogen
bonding network associated with the change of surface composition.
PMID- 17042636
TI - Molecular dynamics simulations of water droplets on polymer surfaces.
AB - Molecular dynamics simulations were used to study the wetting of polymer surfaces
with water. Contact angles of water droplets on crystalline and two amorphous
polyethylene (PE) and poly(vinyl chloride) (PVC) surfaces were extracted from
atomistic simulations. Crystalline surfaces were produced by duplicating the unit
cell of an experimental crystal structure, and amorphous surfaces by pressing the
bulk polymer step by step at elevated temperature between two repulsive grid
surfaces to a target density. Different-sized water droplets on the crystalline
PE surface revealed a slightly positive line tension on the order of 10(-12)-10(
11) N, whereas droplets on crystalline PVC did not yield a definite line tension.
Microscopic contact angles produced by the simple point charge (SPC) water model
were mostly a few degrees smaller than those produced by the extended SPC model,
which, as the model with lowest bulk energy, presents an upper boundary for
contact angles. The macroscopic contact angle for the SPC model was 94 degrees on
crystalline PVC and 113 degrees on crystalline PE. Amorphicity of the surface
increased the water contact angle on PE but decreased it on PVC, for both water
models. If the simulated contact angles on crystalline and amorphous surfaces are
combined in proportion to the crystallinity of the polymer in question, simulated
values in relatively good agreement with measured values are obtained.
PMID- 17042637
TI - On the mechanism of anion desorption from DNA induced by low energy electrons.
AB - Our knowledge of the mechanisms of radiation damage to DNA induced by secondary
electrons is still very limited, mainly due to the large sizes of the system
involved and the complexity of the interactions. To reduce the problem to its
simplest form, we investigated specific electron interactions with one of the
most simple model system of DNA, an oligonucleotide tetrameter compound of the
four bases. We report anion desorption yields from a thin solid film of the
oligonucleotide GCAT induced by the impact of 3-15 eV electrons. All observed
anions (H-, O-, OH-, CN-, and OCN-) are produced by dissociative electron
attachment to the molecule, which results in desorption peaks between 6 and 12
eV. Above 14 eV nonresonant dipolar dissociation dominates the desorption yields.
By comparing the shapes and relative intensities of the anion yield functions
from GCAT physisorbed on a tantalum substrate with those obtained from isolated
DNA basic subunits (i.e., bases, deoxyribose, and phosphate groups) from either
the gas phase or condensed phase experiments, it is possible to obtain more
details on the mechanisms involved in low energy electron damage to DNA,
particularly on those producing single strand breaks.
PMID- 17042638
TI - Nature of reactive O2 and slow CO2 evolution kinetics in CO oxidation by TiO2
supported Au cluster.
AB - Recent experiments on CO oxidation reaction using seven-atom Au clusters
deposited on TiO2 surface correlate CO2 formation with oxygen associated with Au
clusters. We perform first principles calculations using a seven-atom Au cluster
supported on a reduced TiO2 surface to explore potential candidates for the form
of reactive oxygen. These calculations suggest a thermodynamically favorable path
for O2 diffusion along the surface Ti row, resulting in its dissociated state
bound to Au cluster and TiO2 surface. CO can approach along the same path and
react with the O2 so dissociated to form CO2. The origin of the slow kinetic
evolution of products observed in experiments is also investigated and is
attributed to the strong binding of CO2 simultaneously to the Au cluster and the
surface.
PMID- 17042639
TI - Collisions and reactions of gaseous propanol with molten NaOH/KOH.
AB - Molecular beam scattering experiments are used to investigate collisions of a
protic molecule, deuterated 1-propanol (PrOD), with an extremely basic solvent,
the 5149 mol % NaOH/KOH eutectic mixture. This powerful deprotonating medium
readily absorbs PrOD from the gas phase. Nearly all PrOD molecules that
thermalize at the surface of the melt enter the liquid and dissolve for long
times, most likely residing as PrO- after deprotonation by OH-. The PrO-
solvation time is controlled by dissolved H2O, which reprotonates the anion and
liberates D --> H exchanged PrOH. We find no evidence for decomposition of the
alcohol; at the 463 K temperature of the experiments, the hydroxide solution
appears to store propanol reversibly.
PMID- 17042640
TI - Nonlinear optical approach to multiexciton relaxation dynamics in quantum dots.
AB - Unlike the majority of molecular systems quantum dots can accommodate multiple
excitations, which is a particularly important attribute for potential lasing
applications. We demonstrate in this work the concept of using nth order
nonlinear spectroscopies in the transient grating configuration as a means of
selectively exciting (n-1)/2 excitons in a semiconductor and probing the
subsequent relaxation dynamics. We report a direct observation of multiparticle
dynamics on ultrashort time scales through comparison of third and fifth order
experiments for CdSe colloidal quantum dots. Time constants associated with
multiexciton recombination and depopulation dynamics are reported. Deviation from
a Poisson model for the distribution of photoexcited excitons, biexcitons, and
triexcitons is also discussed.
PMID- 17042641
TI - Water properties inside nanoscopic hydrophobic pocket studied by computer
simulations.
AB - The structure and dynamics of water in the vicinity of the hemispherical
hydrophobic pocket of 8 A radius were examined via molecular dynamics simulations
in NVT ensemble. Density, hydrogen bonding properties, and residence times of
water molecules were projected on two-dimensional planes providing a spatial
description of water behavior. We found that the average water density is
significantly depleted relative to bulk value. A detailed analysis of pocket
occupancy revealed fluctuations between states of completely empty pocket and a
pocket filled with a bulklike fluid, which seem to result from collective
behavior of water molecules. Free energy differences accompanying these
fluctuations are rather small, suggesting that the given pocket radius is close
to the critical one for transition between gas and liquid phases in the
considered system. We show that the situation is different in the case of a
simple Lennard-Jones fluid. These results indicate that changing the surface
curvature from flat to concave may lead to qualitative difference in water
behavior in its vicinity. We think that our studies may also put some light on
binding site desolvation process which is necessary to understand to make correct
predictions of binding energies.
PMID- 17042642
TI - Effect of surface tension and surface elasticity of a fluid-fluid interface on
the motion of a particle immersed near the interface.
AB - The motion of a particle immersed in a fluid near a fluid-fluid interface is
studied on the basis of the linearized Navier-Stokes equations. The motion is
influenced by surface tension, dilatational surface elasticity modulus, and
surface shear modulus, as well as by gravity. The backflow at the location of the
particle after a sudden impulse has some universal features that are the same as
for a rigid wall with stick boundary conditions. At short times the flow depends
only on the mass densities of the two fluids. The nature of the short-time flow
is calculated from potential flow theory. At a somewhat later time the particle
shows a pronounced rebound. The maximum value of the rebound and the time at
which the maximum occurs depend on the elastic properties of the interface.
PMID- 17042643
TI - Electronic structure of C60 on Au(887).
AB - We present an analysis of the electronic structure of C60 adsorbed on a vicinal
Au(111) surface at different fullerene coverages using photoemission, x-ray
absorption, and scanning tunneling microscopy/spectroscopy (STS). STS provides a
straightforward determination of the highest occupied molecular orbital (HOMO)
and the lowest unoccupied molecular orbital (LUMO) levels with respect to the
Fermi energy. At C60 coverages of 0.5 and 1 ML a 2.7 eV wide HOMO-LUMO gap is
found. The near-edge x-ray absorption fine structure (NEXAFS) spectrum for the
0.5 ML C60 nanomesh structure displays a significant intensity at the low energy
side of the LUMO exciton peak, which is explained as due to absorption into HOMO
LUMO gap states localized at individual C60 cluster edges. From 0.5 to 1 ML we
observe a rigid shift of the HOMO-LUMO peaks in the STS spectra and an almost
complete quenching of the gap states feature in NEXAFS.
PMID- 17042644
TI - Quantum chemical study of electronic and structural properties of retinal and
some aromatic analogs.
AB - The electronic and structural properties of retinal and four analogs were studied
using semiempirical, ab initio Hartree-Fock, and density functional theory
methods with the aim to evaluate the effects caused by some structural
modifications in the ring bound to the polyenic chain and compared with the all-E
trans-retinal molecule. Therefore, some properties such as bond lengths, bond
angles, atomic charges derived from electrostatic potential charges from
electrostatic potential using grid based method as well as frontier orbitals of
the polyenic chain were analyzed. Furthermore, the transition energies of the
molecules were also calculated using the Zerner's intermediate neglect of
differential overlap-spectroscopic, time-dependent Hartree-Fock, and time
dependent density functional theory methods. The results indicate that in spite
of the structural modifications of retinal derivatives in comparison with all-E
trans-retinal, their properties seem similar. Thus, these molecules may behave
similarly to all-E-trans-retinal and possibly be attempted in the search of novel
molecular devices.
PMID- 17042645
TI - Finite reservoir replica exchange to enhance canonical sampling in rugged energy
surfaces.
AB - A "finite reservoir" replica exchange method is presented to further enhance
sampling upon the regular replica exchange method (REM) in a rugged energy
surface. The present method can facilitate important sampling more efficiently by
exchanging structures with configurations randomly selected from a finite-sized
reservoir; this finite reservoir is pregenerated and updated by a mechanism of
replica exchange with neighboring "temperature" simulations. In practice, this
proposal revises exchange schedule in REM simulations in order to make productive
exchange for conformational "tunneling" more frequent.
PMID- 17042646
TI - Flexibility of phenylene oligomers revealed by single molecule spectroscopy.
AB - The rigidity of a p-phenylene oligomer (p-terphenyl) has been investigated by
single molecule confocal fluorescence microscopy. Two different rylene diimide
dyes attached to the terminal positions of the oligomer allowed for wavelength
selective excitation of the two chromophores. In combination with polarization
modulation the spatial orientation of the transition dipoles of both end groups
could be determined independently. We have analyzed 597 single molecules in two
different polymer hosts, polymethylmethacrylate and Zeonex. On average we find a
22 degrees deviation from the linear gas phase geometry (T = 0 K), indicating a
rather high flexibility of the p-phenylene oligomer independent of the matrix. To
substantiate our experimental results, we have performed quantum chemical
calculations at the density functional theory level for the molecular geometry
and the electronic excitations. Our findings are in agreement with former
experiments on the persistence length of poly(p-phenylenes).
PMID- 17042647
TI - Exact results for noise power spectra in linear biochemical reaction networks.
AB - We present a simple method for determining the exact noise power spectra and
related statistical properties for linear chemical reaction networks. The method
is applied to reaction networks which are representative of biochemical processes
such as gene expression. We find, for example, that a post-translational
modification reaction can reduce the noise associated with gene expression. Our
results also indicate how to coarse grain networks by the elimination of fast
reactions. In this context we have discovered a breakdown of the sum rule which
relates the noise power spectrum to the total noise. The breakdown can be
quantified by a sum rule deficit, which is found to be universal, and can be
attributed to the high-frequency noise in the fast reactions.
PMID- 17042648
TI - Accurate estimation of the density of states from Monte Carlo transition
probability data.
AB - This study develops an efficient approach for calculating the density of states
from energy transition probability matrices generated from extended sampling
Monte Carlo simulations. Direct and iterative variants of the method are shown to
achieve high accuracy when applied to the two-dimensional Ising model for which
the density of states function can be determined exactly. They are also used to
calculate the density of states of lattice protein and Lennard-Jones models which
generate more complex nonzero matrix structures. Whereas the protein simulations
test the method on a system exhibiting a rugged free energy landscape, the
Lennard-Jones calculations highlight implementation details that arise in
applications to continuous energy systems. Density of states results for these
two systems agree with estimates from multiple histogram reweighting,
demonstrating that the new method provides an alternative approach for computing
the thermodynamic properties of complex systems.
PMID- 17042649
TI - Testing one component plasma models on colloidal overcharging phenomena.
AB - In this paper, the mechanisms of overcharging of a colloidal macroion in the
presence of multivalent counterions are investigated by means of Monte Carlo
simulations. This computational technique appears as a powerful tool for probing
the validity of semianalytical models developed for this issue. In particular,
the simulations performed are compared with the predictions of two different
models based on the one component plasma (OCP) theory. Therein, the multivalent
ionic atmosphere confined at the macroion surface is approximated by a two
dimensional Wigner crystal. These kinds of models are largely used in the
literature since (in some cases) they present quite simple equations to describe
the electric double layer (EDL) of macroions with different geometries in the
presence of much smaller (but still multivalent) ions. In this sense, charge
inversion phenomena of membranes, polyelectrolytes, DNA molecules, etc., are
straightforwardly predicted in terms of these expressions. Unfortunately,
comparisons between these predictions and experimental results are scarce, mostly
due to the difficulty to reproduce the experimental conditions in the laboratory.
Accordingly, the goal of the present paper is to simulate EDLs under real
conditions (in which overcharging phenomena are expected to happen) and use the
results obtained in this way for comparing with those obtained from OCP models.
PMID- 17042650
TI - Does equilibrium polymerization describe the dynamic heterogeneity of glass
forming liquids?
AB - A significant body of evidence indicates that particles with excessively high or
low mobility relative to Brownian particles form in dynamic equilibrium in glass
forming liquids. We examine whether these "dynamic heterogeneities" can be
identified with a kind of equilibrium polymerization. This correspondence is
first checked by demonstrating the presence of a striking resemblance between the
temperature dependences of the configurational entropy s(c) in both the theory of
equilibrium polymerization and the generalized entropy theory of glass formation
in polymer melts. Moreover, the multiple characteristic temperatures of glass
formation are also shown to have analogs in the thermodynamics of equilibrium
polymerization, supporting the contention that both processes are varieties of
rounded thermodynamic transitions. We also find that the average cluster mass (or
degree of polymerization) varies in nearly inverse proportionality to s(c). This
inverse relation accords with the basic hypothesis of Adam-Gibbs that the number
of particles in the cooperatively rearranging regions (CRR) of glass-forming
liquids scales inversely to s(c) of the fluid. Our identification of the CRR with
equilibrium polymers is further supported by simulations for a variety of glass
forming liquids that verify the existence of stringlike or polymeric clusters
exhibiting collective particle motion. Moreover, these dynamical clusters have an
exponential length distribution, and the average "string" length grows upon
cooling according to the predictions of equilibrium polymerization theory. The
observed scale of dynamic heterogeneity in glass-forming liquids is found to be
consistent with this type of self-assembly process. Both experiments and
simulations have revealed remarkable similarities between the dynamical
properties of self-assembling and glass-forming liquids, suggesting that the
development of a theory for the dynamics of self-assembling fluids will also
enhance our understanding of relaxation in glass-forming liquids.
PMID- 17042654
TI - Multislice computed tomographic angiography versus digital subtraction
angiography in the follow-up of nitinol stents in the superficial femoral artery.
AB - PURPOSE: To compare quantitative and qualitative parameters obtained from digital
subtraction angiography (DSA) with multislice computed tomographic angiography
(MSCTA) in the follow-up of superficial femoral artery (SFA) stents. METHODS:
Thirteen patients who had SMART stents implanted in the SFA were examined
systematically with DSA and MSCTA (16-row scanner) at 6 months. Quantitative
analysis and morphological assessment were performed on DSA images by an
independent core laboratory, while the MSCTA images were analyzed by 2
radiologists in consensus. DSA measurements included stent length, minimal lumen
diameter and reference diameter at mid stent and 5 mm either side of the stent,
and percentage of stenosis. For MSCTA images, lumen area and the minimum,
maximum, and mean diameters were also recorded. The images were analyzed
qualitatively for diameter stenosis (<50%, 50% to 70%, 71% to 99%, and
occlusion), bends, fractures, and calcifications. RESULTS: There were no
statistical differences between lengths of stented segments, diameter
measurements, or percentages of stenosis from DSA and MSCTA images. The Bland
Altman method showed good agreement between the 2 methods of measurement. MSCTA
detected in-stent proliferation with a diameter stenosis <50% in all 13 cases
diagnosed on DSA (there was no stenosis >50%). There were no bends or stent
fractures on either set of images. The agreement between DSA and MSCTA for the
presence and grading of calcifications was moderate (kappa=0.5). CONCLUSION:
MSCTA provided quantitative and qualitative data comparable with DSA in the
analysis of SFA nitinol stents.
PMID- 17042655
TI - Endovascular repair of dissecting thoracic aortic aneurysm in a patient with
Turner syndrome.
AB - PURPOSE: To report a rare case of dissecting thoracic aortic aneurysm in a young
patient with Turner syndrome owing to complete or partial monosomy of the X
chromosome. CASE REPORT: A 22-year-old patient with Turner syndrome presented
with a 2-month history of voice loss and dysphagia. Multislice computed
tomography (MSCT) disclosed a large (53x75-mm) aneurysm with focal dissection
affecting the distal part of the aortic arch and the proximal descending aorta,
partially involving the left subclavian artery. A TAG endoprosthesis was
implanted without complications. MSCT scans at 3 and 6 months after the procedure
showed good position and patency of the stent-graft, with total exclusion and
shrinkage of the aneurysm. After 1 year of follow-up, she is doing well, without
voice disturbances or dysphagia. CONCLUSION: Although cardiovascular
malformations are common in patients with Turner syndrome, dissecting thoracic
aortic aneurysm is unusual. Stent-graft repair would appear to be feasible in
this situation, but long-term implantation in young patients has not been
explored.
PMID- 17042656
TI - Combined endovascular and surgical treatment of infected carotid-carotid bypass
graft.
AB - PURPOSE: To present a complex case involving an infected carotid-carotid bypass
graft that was successfully treated with a stent-graft and subsequent surgical
removal of the infected graft. CASE REPORT: A 75-year-old woman presented with
persistent purulent drainage of an infected and exposed carotid-carotid
prosthetic bypass graft. Wound cultures revealed methicillin-resistant
Staphylococcus aureus. She was treated with appropriate intravenous antibiotic
therapy without improvement in wound drainage. Because of her comorbid
conditions, a decision was made to pursue endovascular revascularization of her
left and right common carotid arteries (CCA), with subsequent surgical removal of
the infected prosthetic graft. The patient underwent balloon angioplasty; a 7x18
mm Omnilink stent was deployed in the innominate artery and a 7x18-mm Herculink
stent in the ostial left CCA. During the same procedure, the carotid-carotid
bypass graft was excluded with deployment of an 8x50-mm Viabahn stent-graft in
the right CCA. Several days later, the infected and now thrombosed carotid
carotid bypass graft was surgically removed, and an area of adjacent muscle was
used to patch the previously excluded connection of the bypass from the right
CCA. A saphenous vein patch was used to repair the defect in the left CCA. Her
postoperative course was uneventful. At 1 year, the clinical and duplex
examinations revealed satisfactory wound healing and patent left and right CCAs.
CONCLUSION: This case indicates that a combined endovascular and surgical
approach may be a safe and effective option in the treatment of carotid-carotid
bypass graft infection.
PMID- 17042657
TI - Indication for carotid endarterectomy versus carotid stenting for the prevention
of brain embolization from carotid artery plaques: in search of consensus.
PMID- 17042658
TI - Midterm outcomes from the TALON Registry: treating peripherals with SilverHawk:
outcomes collection.
AB - PURPOSE: To determine midterm clinical outcomes among patients with lower
extremity peripheral arterial disease who underwent revascularization with
catheter-based plaque excision (PE). METHODS: Between August 2003 and February
2005, 19 institutions participating in the observational, nonrandomized,
multicenter TALON registry enrolled 601 consecutive patients (353 men; mean age
70+/-11, range 36-98) with 1258 symptomatic lower extremity atherosclerotic
lesions (748 limbs) treated by plaque excision with the SilverHawk catheter.
Approximately 50% of the patients had diabetes, and nearly one third of the
procedures were indicated for Rutherford ischemia category > or =4. Mean lesion
lengths above and below the knee, respectively, were 62.5+/-68.5 mm
(interquartile range [IQR], 20.0-80.0) and 33.4+/-42.7 mm (IQR 15.0-37.5). The
primary endpoints of the study were target lesion revascularization (TLR) at 6
and 12 months. RESULTS: The device achieved < or =50% residual diameter stenosis
in 94.7% of lesions; procedural success was 97.6%. Nearly half (41.9%) of the
procedures involved PE of > or =2 lesions. Nearly three quarters (73.3%) of the
lesions did not require adjunctive therapy, and stent placement following PE
occurred in only 6.3% of lesions. The 6- and 12-month rates of survival free of
TLR were 90% and 80%, respectively. Rates of TLR were similar among patients with
diabetes (11%) and without diabetes (9%). In the multivariate analysis,
significant predictors of TLR at 6 months were a history of MI or coronary
revascularization (HR 5.49, 95% CI 1.87 to 16.10, p=0.0008), multiple (> or =2)
lesions (HR 1.37, 95% CI 1.11 to 1.70, p=0.0019), and increasing Rutherford
category (HR 1.84, 95% CI 1.28 to 2.65, p=0.0003). Lesion length >50 mm was
associated with a 2.9-fold increased risk for TLR (HR 2.88, 95% CI 1.18 to 7.01,
p=0.012); lesion length >100 mm was associated with a 3.3-fold increase in TLR
(HR 3.32, 95% CI 1.15 to 9.56, p=0.016). CONCLUSION: In patients undergoing
revascularization for lower extremity atherosclerotic disease, catheter-based PE
achieves favorable procedural success and avoids the need for repeat
revascularization at midterm follow-up. These findings support PE as a primary
endovascular therapy for patients undergoing lower extremity arterial
revascularization.
PMID- 17042659
TI - Paclitaxel delivered to adventitia attenuates neointima formation without
compromising re-endothelialization after angioplasty in a porcine restenosis
model.
AB - PURPOSE: To investigate the effect of paclitaxel delivered into the adventitia of
pig femoral arteries on neointima formation and hyperplasia as well as re
endothelialization. METHODS: Paclitaxel or vehicle was delivered into the
adventitia of pig femoral arteries using a needle injection catheter following
balloon overstretch. Arteries were then serially examined by angiography, Evan's
blue staining, morphometry, and immunohistochemistry for up to 12 weeks. RESULTS:
Local adventitial delivery of paclitaxel significantly attenuated neointima
formation. The area of neointima (0.41+/-0.17 versus 2.75+/-0.81 mm(2), p<0.01),
the ratio of intima to media (0.12+/-0.05 versus 0.86+/-0.35, p<0.05), and the
degree of stenosis (12.80%+/-3.13% versus 47.06%+/-7.25%, p<0.01) were
significantly lower in the paclitaxel-treated group compared to controls.
Furthermore, cell proliferation was significantly diminished following
adventitial delivery of paclitaxel from day 3 to 21 compared to controls.
Complete re-endothelialization was observed 3 weeks after intervention in both
groups of arteries treated with paclitaxel or vehicle alone. CONCLUSION:
Paclitaxel delivered into the adventitia of pig femoral arteries effectively
attenuates neointima formation after angioplasty without compromising re
endothelialization. Adventitial drug delivery may therefore be an alternative to
drug-eluting stents for the prevention of restenosis.
PMID- 17042660
TI - Sirolimus-eluting stenting of the external carotid artery for the treatment of
ocular ischemia.
AB - PURPOSE: To present a patient in whom severe external carotid artery (ECA)
stenosis causing ocular ischemia was treated with a drug-eluting stent. CASE
REPORT: A 55-year-old woman with severe, diffuse atherosclerosis presented with
impaired left ocular perfusion and amaurosis fugax. Duplex ultrasonography and
angiography documented bilateral occlusion at the origin of the internal carotid
arteries, bilateral subtotal ECA stenoses, and subtotal distal left common
carotid artery (CCA) restenosis following endarterectomy. Percutaneous
revascularization of the left ECA and CCA stenoses was performed using a short
coronary balloon-expandable sirolimus-eluting stent and a self-expanding nitinol
stent, respectively. The procedure was uneventful, and the ocular symptoms
resolved. At 6 months, the patient remained asymptomatic, with angiographically
patent stents. CONCLUSION: Drug-eluting stenting may be a novel option to treat
symptomatic ECA stenosis.
PMID- 17042661
TI - Percutaneous laser-facilitated thrombectomy: an innovative, easily applied, and
effective therapeutic option for recanalization of acute and subacute thrombotic
hemodialysis shunt occlusions.
AB - PURPOSE: To report our experience with excimer laser-facilitated recanalization
of acute and subacute thrombotic occlusions of hemodialysis shunts. METHODS:
Twenty-one patients (16 women; mean age 54+/-19 years, range 31-76) presented
with acute and subacute thrombotic occlusions of their hemodialysis shunts (4
Cimino, 17 prosthetic; 18 forearm, 3 upper arm); mean occlusion time was 4.1+/-3
days (range 1-14), and the thrombotic occlusion measured a mean 17.4+/-9 cm
(range 5-27). Fresh thrombus was observed in addition to the total shunt
occlusion in all cases. All patients were treated initially with a pulsed
ultraviolet (308-nm) excimer laser. Eighteen (85.7%) patients received adjunctive
local thrombolysis for treatment of residual thrombus. Nineteen (90.5%) patients
underwent angioplasty of the underlying anastomotic stenosis. RESULTS: The
angiographic occlusion was reduced from 100% to 63%+/-28% after laser treatment
and to 36%+/-18% after 1 hour of thrombolytic therapy (20 mg tissue plasminogen
activator). TIMI flow increased significantly from grade 0 to 2.7+/-0.5 following
laser ablation (p<0.001) and to 3.0+/-0.2 upon completion of the angioplasty
procedure (p>0.001 versus baseline). The immediate procedural success was 95.2%
(20/21). Detectable thrombotic embolization and laser-related complications were
not observed in any case. Primary patency was 85%; 3 patients had abnormal
Doppler flow within 6 weeks and underwent reintervention (secondary patency
100%). All successfully treated shunts were usable for further dialysis at the 6
week follow-up. CONCLUSION: Percutaneous excimer laser-facilitated thrombus
vaporization is safe and effective for recanalization of acute and subacute
thrombotic occlusions of hemodialysis shunts.
PMID- 17042662
TI - Does N-acetylcysteine prevent contrast-induced nephropathy during endovascular
AAA repair? A randomized controlled pilot study.
AB - PURPOSE: To examine if N-acetylcysteine (NAC) reduces the incidence of contrast
nephropathy during endovascular abdominal aortic aneurysm repair (EVAR) as
evidenced by changes in markers of renal function. METHODS: Twenty consecutive
men (mean age 72 years, range 65-79) undergoing EVAR were randomized to receive
standard intravenous fluid hydration or standard fluid hydration and NAC (600 mg
BID orally, 4 doses). Venous blood and urine were collected prior to the
procedure and for 5 postoperative days and analyzed blindly for serum creatinine,
urinary retinol-binding protein (RBP), and albumin/creatinine ratio (ACR).
RESULTS: There were no significant differences in baseline demographics between
the groups. No patient developed acute renal failure. In both groups, urinary RBP
rose significantly from baseline (median 15 microg/mmol to peak 699 microg/mmol
in controls versus 17 to 648 microg/mmol in the treatment group, p<0.003). There
were similar significant rises in ACR (p<0.02). There was, however, no
significant difference in the postoperative RBP or ACR between the groups at any
time point. CONCLUSION: EVAR causes significant acute renal injury in most
patients. This was not attenuated by N-acetylcysteine. The causes of renal injury
are probably multifactorial, the long-term clinical significance of which is
unclear.
PMID- 17042663
TI - Intentional coverage of a main renal artery during endovascular juxtarenal aortic
aneurysm repair in symptomatic high-risk patients.
AB - PURPOSE: To describe the efficacy and morbidity of intentionally covering a main
renal artery during symptomatic juxtarenal endovascular aneurysm repair (EVAR).
CASE REPORTS: Two patients with symptomatic juxtarenal abdominal aortic aneurysm
(AAA) were felt to be at prohibitive risk for open repair. Each underwent EVAR
with intentional coverage of 1 main renal artery to achieve adequate proximal
hemostatic seal. One patient died at 24 months; the second is symptom-free at 10
months. Both aneurysms initially decreased in diameter. Both patients had
increased serum creatinine and required increased therapy for hypertension, but
neither required hemodialysis. Renal volume decreased 48.7% and 68.0%,
respectively. CONCLUSION: Intentional coverage of a main renal artery during EVAR
for a symptomatic juxtarenal aneurysm resulted in effective short-term AAA repair
with no need for dialysis. Despite the increased requirement for antihypertensive
medications and the observed decline in renal function, this technique provides
an option for treatment of this difficult patient subset.
PMID- 17042664
TI - EndoFit stent-graft repair of isolated common iliac artery aneurysms with short
necks.
AB - PURPOSE: To evaluate the feasibility and efficacy of repairing isolated iliac
artery aneurysms with short proximal necks (<10 mm) by implanting the EndoFit
stent-graft. METHODS: Seven patients (6 men; median age 73 years, range 70-78)
were diagnosed with an isolated common iliac artery (CIA) aneurysm that featured
a short proximal landing zone, complicating endovascular treatment. The median
aneurysm diameter was 4.4 cm (range 3.5-7.0), and the median proximal neck length
was 7 mm (range 5-9).The aneurysms were treated using the EndoFit stent-graft,
which can be deployed in a short proximal landing zone. The modified technique
involves the deployment of the graft directly above the aneurysm sac without
obstructing the contralateral iliac axis, thus affixing the bare proximal stent
in the terminal aorta. Follow-up was performed by clinical evaluation and
computed tomography at 1, 6, and 12 months postoperatively. RESULTS: The EndoFit
stent-graft was successfully deployed in all cases, with complete aneurysm
exclusion. In 1 case, the deployment of a second cuff was necessary to secure
complete aneurysm exclusion. The median follow-up was 18 months, during which no
deaths occurred, and no endoleak or stent-graft migration was observed. Endograft
thrombosis occurred in 1 case due to graft angulation caused by external iliac
artery stenosis and kinking. None of the aneurysms has ruptured, and there have
been no serious complications. CONCLUSION: Direct endoluminal repair of isolated
CIA aneurysms with short proximal necks is feasible using this technique.
Efficacy and long-term results are to be confirmed by larger scale series over a
long time period.
PMID- 17042665
TI - Factors influencing the need for target vessel revascularization after renal
artery stenting.
AB - PURPOSE: To provide additional insight into factors that may be associated with
the need for target vessel revascularization (TVR) following de novo renal artery
stenting during long-term follow-up. METHODS: A retrospective chart and database
review was conducted to analyze the progress of all patients with de novo
symptomatic renal artery stenosis who underwent stent-supported angioplasty under
the auspices of the Single Operator, Single Center, Renal Stent Retrospective
Study (SOCRATES). The records review identified 782 patients who were enrolled in
the study between 1993 and 2004; after excluding 34 (4.5%) patients (lost to
follow-up or inadequate data), 748 consecutive patients (412 women; mean age
70.7+/-9.7 years, range 37-92) were suitable for longitudinal analysis. The need
for TVR was based on strict clinical criteria (> or =20% rise in serum
creatinine, worsening hypertension, and/or recurrent flash pulmonary edema), and
all patients underwent multidisciplinary evaluation before stenting and during
follow-up. RESULTS: Follow-up spanned a mean 45.8+/-26.5 months. TVR was needed
in 88 (10.03%) of 877 arteries and was best predicted by patient age < or =67
years (OR 2.91, p=0.0001), stent diameter < or =5.0 mm (OR 2.31, p=0.001),
solitary functioning kidney (OR 2.01, p=0.048), history of lower extremity
peripheral artery disease (OR 1.87, p=0.008), and antecedent history of stroke
(OR 1.73, p=0.026). CONCLUSION: Renal artery stenting appears to be durable, with
only 10% of stented arteries requiring TVR during clinically-based long-term
follow-up. Arteries with a final stent diameter < or =5.0 mm were more than twice
as likely to need TVR, as were patients with a solitary kidney. The authors
acknowledge that clinical recurrence is not a surrogate for ultrasound
surveillance after renal artery stenting, so prospective controlled trials will
be needed to determine risk factors for restenosis.
PMID- 17042666
TI - Evolution and future of preclinical testing for endovascular grafts.
AB - The preclinical testing of endovascular grafts has evolved significantly since
the creation and early testing of these devices; however, there are continued
limitations in using preclinical testing to predict clinical performance. Early
testing was conducted in the absence of standards and guidance specific to
endovascular grafts, and references available for vascular grafts and stents did
not adequately account for the complexity of endovascular graft systems. Failure
of early-generation devices suggested that the testing being conducted was
inadequate and that there was a lack of understanding of the in vivo environment.
These concerns led to several efforts to improve preclinical testing. The Food
and Drug Administration (FDA) sponsored a workshop to discuss the limitations
inherent in testing of endovascular grafts, and an ISO standard for endovascular
grafts was developed. Publication of the standard in 2003 succeeded in
standardizing testing and reporting across device manufacturers; however, several
clinical failure modes, such as migration and stent fractures, continued to be
unpredicted by current preclinical testing. This, coupled with knowledge gained
from additional clinical experience, led the FDA to hold a second workshop to
discuss the benefits and limitations of current testing and propose future
testing that may better predict device performance. This workshop was successful
in accurately describing past testing, determining what has been learned,
identifying issues that have not been adequately addressed, proposing
modifications to address these limitations, and discussing how the proposed
modifications should be implemented. While significant progress has been made in
endovascular graft testing, continued collaboration among industry, academia,
regulators, and clinicians will provide continued improvement in the
predictability of device performance.
PMID- 17042667
TI - Late perforation of a thoracic aortic dacron graft by a metallic stent-graft
component.
AB - PURPOSE: To describe a case involving perforation of a previously placed aortic
Dacron graft by the uncovered proximal stent of a thoracic stent-graft. CASE
REPORT: A 76-year-old man with a surgically treated type A dissection presented
with residual type B dissection. Thoracic stent-grafting of the entry site was
performed successfully. After 2 years, the patient was admitted for evaluation of
a non-pulsating parasternal mass. Computed tomography showed a large, hypodense
liquid-like mass affecting the mediastinum up to the subcutaneous tissue. A false
aneurysm at the proximal end of the stent-graft was observed arising from an
aortic perforation by the uncovered stent. One week later, the mass had almost
completely resolved, and the patient has been scheduled for close surveillance.
CONCLUSION: This case illustrated the importance of thoroughly examining the long
term durability and compatibility of prosthetic materials.
PMID- 17042668
TI - Influence of infrarenal neck length on outcome of endovascular abdominal aortic
aneurysm repair.
AB - PURPOSE: To evaluate the influence of the infrarenal neck length on clinical
outcome after endovascular abdominal aortic aneurysm repair (EVAR). METHODS: Data
were analyzed from 3499 patients enrolled in the EUROSTAR registry between
January 1999 and April 2005 who underwent EVAR with a Talent or Zenith endograft
and had detailed morphological data recorded. The study cohort was divided into 3
groups according to infrarenal neck length: >15 mm (reference group A, n=2822),
11 to 15 mm (group B, n=485), and < or =10 mm (group C, n=192). Uni- and
multivariate analyses were performed to evaluate differences in clinical outcomes
among the study groups. RESULTS: After correction for confounders, proximal type
I endoleak within 30 days occurred in 10.9% of group C compared to 2.6% of group
A (OR 4.46, 95% CI 2.61 to 7.61). Within 48 months of follow-up (median 12
months), the incidence of proximal endoleaks was higher in groups B (9.6%; HR
1.98, 95% CI 1.16 to 3.38) and C (11.3%; HR 2.132, 95% CI 1.17 to 4.60) compared
to group A (3.4%). CONCLUSION: Our study indicates that endovascular treatment of
abdominal aortic aneurysms with infrarenal neck length <15 mm is associated with
significantly increased risk of short- and midterm proximal endoleaks after EVAR.
The greater risk of proximal endoleaks should be weighed against the risks of
alternative treatment modalities.
PMID- 17042669
TI - Iliac anastomotic stenting with a sirolimus-eluting biodegradable poly-L-lactide
stent: a preliminary study after 6 weeks.
AB - PURPOSE: To assess technical feasibility and biocompatibility of a new
biodegradable sirolimus-eluting poly-L-lactide (PLLA) vascular anastomotic stent.
METHODS: A polytetrafluoroethylene bifurcated graft was implanted in 9 pigs
through a midline abdominal incision. After transverse graft limb incision, 6
unloaded PLLAs, 6 sirolimus-loaded PLLAs, and 6 unloaded stainless steel (316L)
stents were randomly implanted at both iliac anastomotic sites. Stents were
deployed with a 6-mm balloon under direct vision without the use of angiography.
Prior to sacrifice after 6 weeks, contrast-enhanced computed tomography (CT) was
performed to determine patency of the target vessels. Stented segments were
surgically explanted and processed for histology to measure the mean luminal
diameter and intimal thickness and to assign vascular injury and inflammation
scores. RESULTS: No animals were lost during the study period. All stented graft
limbs were patent on CT and histology. At the anastomotic sites and iliac
arteries, the mean luminal diameter of SIR-PLLA stents (4.11+/-0.15 and 4.08+/
0.13 mm, respectively) were comparable to metal stents (4.23+/-0.35 and 4.21+/
0.26 mm, respectively), but significantly higher compared to unloaded PLLA stents
[3.32+/-0.56 mm (p<0.001) and 3.29+/-0.39 mm (p=0.013), respectively]. At the
iliac arteries, the mean intimal thickness was significantly lower with SIR-PLLA
stents (0.09+/-0.02 mm) compared to unloaded PLLA stents (0.31+/-0.15 mm,
p<0.001) and metal stents (0.19+/-0.04 mm, p=0.004). Vascular injury scores
demonstrated only mild vascular trauma for all stents (SIR-PLLA: 0.42+/-0.63,
PLLA: 0.51+/-0.62, metal: 0.50+/-0.62). Only mild inflammatory reaction was noted
around SIR-PLLA stent struts (1.14+/-0.46), which was comparable to metal stents
(1.27+/-0.45) but significantly lower than PLLA stents (1.79+/-0.56, p<0.001).
CONCLUSION: SIR-PLLA stents showed comparable luminal diameter compared to metal
stents, so incorporating sirolimus could reduce the inflammatory and neointimal
response to PLLA stents. These findings need to be assessed with longer follow-up
to confirm maintenance of efficacy.
PMID- 17042671
TI - Regarding "Distal embolism during percutaneous revascularization of infra-aortic
arterial occlusive disease: an underestimated phenomenon".
PMID- 17042673
TI - An assessment of statin safety.
AB - Recently, statin safety and potential drug interactions have received close
attention in the consumer and medical press. In particular, rosuvastatin, the
most recent statin introduced into the US market, has been the object of much
speculation. Many of these reports have lost sight of the proven efficacy of
statins in coronary disease prevention at a time when coronary heart disease is
the number one killer of adults, and have failed to frame the potential drug
toxicity in the context of this benefit. Summarized here are the conclusions of
the National Lipid Association's Statin Safety Assessment Task Force, which
reviewed extensive new drug application (NDA) and postmarketing data for all the
currently marketed statins regarding their effect on the liver, muscle, renal,
and neurologic systems. The task force found that, overall, hepatic, renal, or
neurologic function does not appear to be compromised by statin use. They do not
recommend routine monitoring of these systems but do recommend ongoing
surveillance of symptomatic patients. With respect to muscle toxicity, the task
force's Muscle Expert Panel concluded that the incidence of myopathy and
rhabdomyolysis is low and appears to be dose-related, rather than associated with
the degree of low-density lipoprotein cholesterol lowering and also appears to be
related to the individual statin used. For example, from the rosuvastatin NDA
database and additional postmarketing data, the overall incidence of myopathy was
found to be lower than that observed with other statins. Administrative claims
data of hospitalization rates for adverse events in statin patients confirm the
task force conclusion that, overall, statins are safe and well tolerated when
used as monotherapy.
PMID- 17042674
TI - Rising to the challenge of treating high-risk patients.
AB - Guidelines from the National Cholesterol Education Program (NCEP) Adult Treatment
Panel III (ATP III) focus the need for the most intensive efforts to lower low
density lipoprotein cholesterol (LDL-C) in the patients at greatest risk of a
major future clinical coronary heart disease event. Major clinical trials, such
as Pravastatin or Atorvastatin Evaluation and Infection Therapy and the Heart
Protection Study, demonstrated the value of lowering LDL-C levels in high-risk
patients to well below the ATP III target of <100 mg/dL. In 2004, the NCEP
writing group suggested that a more aggressive LDL-C goal of <70 mg/dL is an
option when treating high-risk patients, particularly those with the presence of
established cardiovascular disease plus major multiple risk factors (especially
diabetes), severe and poorly controlled risk factors (ie, cigarette smoking),
multiple criteria of the metabolic syndrome, or an acute coronary syndrome. With
stricter targets, high-risk patients are less likely to achieve their cholesterol
goals than lower risk patients. Recent large trials comparing rosuvastatin with
other statin monotherapies have shown a greater LDL-C reduction and better
attainment of goals with rosuvastatin. In addition, the MERCURY [Measuring
Effective Reductions in Cholesterol Using Rosuvastatin Therapy] trials
demonstrate that switching to rosuvastatin significantly increased the percentage
of patients who achieved their ATP III LDL-C targets.
PMID- 17042675
TI - Cost efficiency and formulary considerations for statin therapy.
AB - Extensive epidemiologic evidence and reports issued by the National Cholesterol
Education Program have repeatedly identified low-density lipoprotein cholesterol
(LDL-C) as the primary target in reducing the primary and secondary risk of
coronary events. With recent evidence supporting a more aggressive approach using
higher potency statins, and a lower threshold for initiating drug therapy for
high-risk patients, providers and administrators in managed care are charged with
finding the most effective and cost-effective means of attaining these goals.
Changes in the market, such as newer high-potency statins and statin combinations
available at lower cost and expiration of patents on widely accepted brand drugs,
have provided practitioners with the ability to reduce LDL-C at lower costs than
ever. The cost-efficiency analysis presented here finds that, for low-to-moderate
reduction (<40%), generic lovastatin and simvastatin provide the lowest cost per
1% LDL-C reduction. Similarly, for reduction greater than 40%, branded
rosuvastatin and ezetimibe/simvastatin have the lowest cost per 1% reduction.
PMID- 17042676
TI - Iodine nutrition requirements during pregnancy.
PMID- 17042677
TI - Iodine supplementation for pregnancy and lactation-United States and Canada:
recommendations of the American Thyroid Association.
AB - The fetus is totally dependent in early pregnancy on maternal thyroxine for
normal brain development. Adequate maternal dietary intake of iodine during
pregnancy is essential for maternal thyroxine production and later for thyroid
function in the fetus. If iodine insufficiency leads to inadequate production of
thyroid hormones and hypothyroidism during pregnancy, then irreversible fetal
brain damage can result. In the United States, the median urinary iodine (UI) was
168 microg/L in 2001-2002, well within the range of normal established by the
World Health Organization (WHO), but whereas the UI of pregnant women (173
microg/L; 95% CI 75-229 microg/L) was within the range recommended by WHO (150
249 microg/L), the lower 95% CI was less than 150 microg/L. Therefore, until
additional physiologic data are available to make a better judgment, the American
Thyroid Association recommends that women receive 150 microg iodine supplements
daily during pregnancy and lactation and that all prenatal vitamin/mineral
preparations contain 150 microg of iodine.
PMID- 17042679
TI - Peripheral cytokine expression in autoimmune thyroiditis: effects of in vitro
modulation by rosiglitazone and dexamethasone.
AB - BACKGROUND: In Hashimoto's thyroiditis (HT), there is evidence for activation of
peripheral T-lymphocytes that predominantly express a T helper 1 (T(H)1) cytokine
bias. However, the immunomodulatory factors involved in regulating this response
have so far received scant attention. In this study, we examine the effects of
the glucocorticoid, dexamethasone, and the peroxisome proliferator-activated
receptor-gamma (PPAR-gamma) ligand, rosiglitazone on the expression of interferon
(IFN)-gamma (T(H)1) and interleukin (IL)-4 (T(H)2) by activated peripheral CD4(+)
and CD8(+) lymphocytes in patients with HT (n = 10) and healthy control subjects
(n = 12). METHODS: Peripheral blood mononuclear cells (PBMC) were stimulated in
vitro with phorbolmyristate acetate (PMA) and ionomycin in the presence or
absence of varying doses of dexamethasone and rosiglitazone (0.01 microM, 1.0
microM, and 100 microM). Cytokine expression was determined by flow cytometry.
RESULTS: CD4(+) and CD8(+) IFN-gamma expression was greater in HT than controls
(14.87 versus 9.25; p < 0.05 and 21.34 versus 10.16; p < 0.01, respectively). A
dose-dependent inhibition of IFN-gamma expression was seen with dexamethasone and
rosiglitazone. Inhibition of CD4(+) and CD8(+) IFN-gamma expression with both
dexamethasone and rosiglitazone was greater in control subjects than in patients
(p < 0.05). There was no significant difference in IL-4 expression between
patients and control groups and its expression remained unaffected by either
compound. CONCLUSIONS: We show that CD4(+) and CD8(+) T lymphocytes from HT
patients express a type 1 cytokine bias that is significantly more resistant to
in vitro modulation by rosiglitazone and dexamethasone. Further studies are
needed to clarify if this resistance plays a role in the pathogenesis of
autoimmune thyroid disease (AITD).
PMID- 17042680
TI - Effect of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary
axis in rats.
AB - OBJECTIVE: Deficiencies of vitamin A and iodine are common in many developing
countries. Vitamin A deficiency (VAD) may adversely affect thyroid metabolism.
The study aim was to investigate the effects of concurrent vitamin A and iodine
deficiencies on the thyroid-pituitary axis in rats. DESIGN: Weanling rats (n =
56) were fed diets deficient in vitamin A (VAD group), iodine (ID group), vitamin
A and iodine (VAD + ID group), or sufficient in both vitamin A and iodine
(control) for 30 days in a pair-fed design. Serum retinol (SR), thyroid hormones
(FT(4), TT(4), FT(3), and TT(3)), serum thyrotropin (TSH), pituitary TSHbeta mRNA
expression levels, and thyroid weights were determined at the end of the
depletion period. MAIN OUTCOME: Compared to the control and ID groups, SR
concentrations were about 35% lower in the VAD and VAD + ID groups (p < 0.001),
indicating moderate VA deficiency. Comparing the VAD and control groups, there
were no significant differences in TSH, TSHbeta mRNA, thyroid weight, or thyroid
hormone levels. Compared to the control group, serum TSH, TSHbeta mRNA, and
thyroid weight were higher (p < 0.05), and FT4 and TT4 were lower (p < 0.001), in
the VAD + ID and ID groups. Compared to the ID group, TSH, TSHbeta mRNA, and
thyroid weight were higher (p < 0.01) and FT(4) and TT(4) were lower (p < 0.001)
in the VAD + ID group. There were no significant differences in TT3 or FT3
concentrations among groups. CONCLUSION: Moderate VAD alone has no measurable
effect on the pituitary-thyroid axis. Concurrent ID and VAD produce more severe
primary hypothyroidism than ID alone.
PMID- 17042681
TI - Study of serum antibodies against three eye muscle antigens and the connective
tissue antigen collagen XIII in patients with Graves' disease with and without
ophthalmopathy: correlation with clinical features.
AB - OBJECTIVE: The extraocular muscles are one of the primary tissues implicated in
the autoimmune-mediated inflammation of thyroid-associated ophthalmopathy (TAO).
Our aim was to determine the prevalence and level of antibodies against three
candidate eye muscle antigens and the orbital fibroblast membrane antigen
collagen XIII, in well-characterized patient groups. STUDY DESIGN AND PATIENTS:
The study cohort consisted of patients with Graves' hyperthyroidism with and
without ophthalmopathy, controls patients with other thyroid or other autoimmune
disorders and healthy subjects. The presence of eye muscle antibodies was
determined using an optimized and standardized enzyme-linked immunosorbent assay.
We measured antibodies against (i) the 67-kDa flavoprotein (Fp) subunit of the
mitochondrial enzyme succinate dehydrogenase; (ii) G2s, a 141 amino acid fragment
of the winged-helix transcription factor FOXP1; (iii) calsequestrin, a 63-kDa
calcium-binding protein; and (iv) collagen XIII, a connective tissue protein that
is closely linked to the congestive ophthalmopathy subtype of TAO. Eye muscle
antibody levels were correlated with clinical diagnosis and presence or not of
ophthalmopathy. RESULTS: Prevalences of positive antibody tests to calsequestrin
(75.0%) and collagen XIII (43.8%) were significantly greater in Graves' disease
(GD) patients with ophthalmopathy than in healthy subjects, whereas modest
significance was demonstrated with antibodies against Fp, but not G2s.
Significantly greater serum levels of antibodies against calsequestrin, G2s, and
collagen XIII, but not Fp, were found in GD patients with ophthalmopathy compared
to control patients without eye disease and healthy subjects. CONCLUSIONS:
Calsequestrin and collagen XIII antibodies are the most specific to TAO, whereas
antibodies against G2s, and to a lesser extent Fp, are also markers of
ophthalmopathy, but less reliable. These results are unique in that it is the
first time the significance of a panel of three candidate eye muscle antibodies
and a connective tissue antibody have been evaluated in the same patients with
ophthalmopathy.
PMID- 17042682
TI - Fine-needle aspiration biopsy of thyroid lesions processed by thin-layer
cytology: one-year institutional experience with histologic correlation.
AB - Fine-needle aspiration biopsy (FNAB) is important for classifying thyroid
lesions. Thin-layer cytology (TLC) has been adopted in thyroid cytology with
encouraging results and its efficacy in diagnosing nodular lesions in a 1-year
period was evaluated. All 2006 thyroid FNAB processed by TLC only in the year
2004 were examined. The 2002 and 2003 series, processed both by TLC and
conventional smears (CS), were used as controls. All FNAB were classified
according to previously published morphologic criteria. Surgery was performed on
311 cases: all 98 benign and 30 malignant lesions were histologically confirmed.
The inadequate diagnoses resulted 11.3% in 2004, 13.3% in 2003, and 18.2% in
2002. The indeterminate diagnosis rate was 16.9% in 2004, 20.7% in 2003, and
24.8% in 2002. Sensitivity, specificity, and diagnostic accuracy values ranged
from 80% to 100%. TLC is useful in reducing inadequate and indeterminate cases
without decreasing the preoperative diagnostic accuracy. Ancillary techniques can
be successfully applied to the stored material.
PMID- 17042683
TI - Usefulness of ultrasonography for diagnosis of malignant lymphoma of the thyroid.
AB - BACKGROUND: Recent developments in ultrasonography (US) and the prevalence of
ultrasound-guided fine needle aspiration biopsy (US-FNAB) has enabled physicians
to detect and diagnosis thyroid diseases, including thyroid malignant lymphoma,
much more easily. METHODS: We describe our diagnostic strategy for malignant
lymphoma on US screening. We screened possible malignant lymphoma patients by US
characteristics such as enhanced posterior echoes. RESULTS: Among 170 patients
suspected of malignant lymphoma between 2000 and 2004, 74 (43.5%) were also
diagnosed as having or suspected of lymphoma by US-FNAB. Five patients dropped
out, and 67 of 69 patients who underwent surgical examination were pathologically
diagnosed as having lymphoma. Finally, 79 (47.9%) of 165 US-suspected patients
were confirmed as having lymphoma. Only 21.5% of lymphoma patients complained of
rapidly growing goiter. CONCLUSION: US screening for goiters contributes markedly
to diagnosis of lymphoma at an early phase, facilitating early initiation of
therapy.
PMID- 17042684
TI - Thyroid color flow Doppler sonography: an adjunctive tool for differentiating
patients with inappropriate thyrotropin (TSH) secretion due to TSH-secreting
pituitary adenoma or resistance to thyroid hormone.
AB - BACKGROUND: Thyrotropin (TSH)-secreting pituitary adenoma (TSHoma) and resistance
to thyroid hormone (RTH) are two forms of inappropriate TSH secretion. Thyroid
blood flow is largely TSH dependent. OBJECTIVE: To assess whether thyroid blood
flow may help to differentiate TSHoma and RTH. DESIGN: Intrathyroidal color flow
Doppler sonography (CFDS) pattern and peak systolic velocity (PSV) were assessed
at baseline and during T(3) suppression test on eight consecutive patients with
TSHoma and 10 with RTH. MAIN OUTCOME: All controls had CFDS pattern 0. Three RTH
patients had pattern I and seven had pattern II. Two TSHoma patients had pattern
I, five had pattern II, and one had pattern III. PSV at baseline was 3.8 +/- 1.3
cm/s in controls, 8.8 +/- 2.5 cm/s in RTH, 11.1 +/- 2.7 cm/s in TSHoma (p <
0.0003 vs. controls, p = 0.087 RTH vs. TSHoma). After T3 suppression test, PSV
values were lower in RTH than in TSHoma (4.6 +/- 1.8 vs. 7.7 +/- 2.6 cm/s, p =
0.008). PSV values and CFDS pattern normalized in nine and eight RTH patients,
respectively, after T(3) suppression test; conversely, only one TSHoma patient
had a normalization of PSV values, and none had a normalization of CFDS pattern
(p < 0.003 vs. RTH). CONCLUSIONS: Both RTH and TSHoma have increased CFDS pattern
and PSV values; however, after T(3) both parameters normalized in most patients
with RTH but not in those with TSHoma. Accordingly, CFDS pattern and PSV are
adjunctive tools to differentiate these two forms of inappropriate TSH secretion.
PMID- 17042685
TI - Scanning electron microscopy of thyroid cells under fully hydrated conditions--a
novel technique for a seasoned procedure: a brief observation.
AB - Technical information for handling fine-needle aspiration samples from thyroid
lesions for WETSEM electron microscopy is presented. The use of wet SEM
technology maintains cytological features of the thyroid cells, in the
atmospheric electronic microscope chamber without the need for solidification.
Images are presented from normal and pathological thyroid specimens showing
subcellular elements unavailable to the cytopathologist by light microscopy. Of
24 samples, 18 were adequate for clinical evaluation. In 16 of these 18
specimens, we could find features compatible with the final histological or
cytological diagnosis (post-hoc). In two cases, the cell features were too unique
to be interpretable. Because this procedure is relatively simple, there is
potential for the use of this technology as an adjunct to light microscopy in
clinical and research settings.
PMID- 17042686
TI - Perceptions of diagnostic terminology and cytopathologic reporting of fine-needle
aspiration biopsies of thyroid nodules: a survey of clinicians and pathologists.
AB - INTRODUCTION: Guidelines on thyroid fine-needle aspiration biopsy (FNABs)
reporting calls for unambiguous diagnostic terminology in order to maximize
treatment. This study evaluates how pathologists follow the guidelines and
clinicians understand the diagnostic categories in terms of patient care. DESIGN:
Survey 1 asked pathologists who perform/interpret FNABs which of "atypical,"
"indeterminate," "suspicious," and "nondiagnostic" they routinely use. Survey 2
asked clinicians who treat thyroid nodules to correlate these categories to the
options of "negative FNAB/follow-up," "repeat FNAB," and "proceed to surgery."
The anonymous, voluntary results were entered into a database and analyzed. MAIN
OUTCOME: Pathologists' and clinicians' response rates were 70% and 35%,
respectively. Survey 1: 27% of pathologists used three, 27% used one, and 44%
used two categories. Survey 2: 98% clinicians would repeat the FNAB with a
"nondiagnostic" and 96% opted for surgery with a "suspicious" diagnosis.
"Indeterminate" prompted 58% to repeat the FNAB and 32% to send the patient to
surgery. "Atypical" would lead 37% to repeat the FNAB and 52% to send the patient
to surgery. CONCLUSIONS: Pathologists actively use the terminology "suspicious,"
"indeterminate," or "atypical," which cause confusion in some clinicians. These
results support the need for a more standardized terminology for FNAB reporting
and education of the clinicians on that terminology.
PMID- 17042687
TI - Thyroid disorders in employees of a nuclear power plant.
AB - BACKGROUND: The thyroid gland is a potential target organ for radiation-related
damage. The aim of this analysis was to investigate the association between
occupational exposure to ionizing radiation and the risk of autoimmune thyroid
disease as well as thyroid nodules and dysfunction in workers of a former nuclear
power station. METHODS: Seventy-one male power station workers 38 to 57 years of
age who had been exposed to a lifetime dose in the upper allowed range
(accumulated lifetime dose 70 to 400 mSv) were compared to a population-based
sample of 670 males who were not exposed to occupational radiation. Thyroid
ultrasound was performed by the same observers. Laboratory parameters were
analyzed in a central laboratory. RESULTS: After controlling analyses for age and
further relevant confounders no significant differences with respect to thyroid
nodules and markers of autoimmune thyroid disease were detected between exposed
and nonexposed individuals. However, nuclear power plant employees had higher
odds for elevated serum thyrotropin (TSH) levels than the reference group (odds
ratio 4.54; 95% confidence interval 1.43; 13.91). CONCLUSIONS: Workers of a
nuclear power plant with occupational exposure to ionizing radiation within the
upper allowed dose range have an increased risk of elevated serum TSH levels.
Further studies are required to confirm possible effects of occupational exposure
to radiation on thyroid function.
PMID- 17042688
TI - The relative frequency in which empiric dosages of radioiodine would potentially
overtreat or undertreat patients who have metastatic well-differentiated thyroid
cancer.
AB - The dosage of (131)I for the treatment of metastatic well-differentiated thyroid
cancer is typically selected empirically. Benua and Leeper implemented a method
to estimate the maximum dosages of (131)I that could be administered to a patient
so as not to exceed a maximum tolerated radiation absorbed dose (MTD), which was
defined as 200 rads (cGy) to the blood. The objective of this study was to
determine the frequency of (131)I treatments in which the patient (1) would have
exceeded the MTD (i.e., overtreatment) or (2) would have been able to receive
higher dosages of (131)I thereby delivering a potentially higher radiation
absorbed dose to their metastases (i.e., undertreatment) had the patient been
administered various assumed empiric dosages of (131)I. The dosimetrically
determined maximum tolerated radioactivities (MTA) to deliver 200 rads to the
blood (MTD) were tabulated at our facility. Data were then grouped to determine
the percentage of patients who would have received less than or more than the MTD
for various assumed empiric dosages of (131)I. A total of 127 dosimetries were
performed. For assumed empiric dosages of (131)I (100 mCi, 150 mCi, 200 mCi, 250
mCi, and 300 mCi), the percentage of treatments for which patients would have
exceeded the MTD were less than 1%, 5%, 11%, 17%, and 22%, respectively, and
could have received a higher dosage of (131)I were more than 99%, 95%, 89%, 83%,
and 78%, respectively. A significant number of patients receiving various empiric
dosages of (131)I may exceed 200 rads (cGy) to the blood (potential
overtreating). Likewise, the majority of patients may be able to receive much
higher dosages of (131)I relative to empiric dosages thereby delivering
potentially higher radiation absorbed doses to the metastases without exceeding
200 rads (cGy) to the blood (potential undertreating).
PMID- 17042689
TI - Defective efficacy of retinoic acid treatment in patients with metastatic thyroid
carcinoma.
AB - Radioiodine (I-131) therapy is of proven efficacy for differentiated thyroid
carcinoma. However, its efficacy relies on specific uptake mechanisms, which may
be lost during the evolution of the disease. Attempts to increase the iodine
uptake of such tumors have been made using retinoic acid because it exerts
redifferentiating effects on thyrocytes. This study aims to assess the capability
of the retinoic acid (RA) treatment to reinforce iodine 131-irradiation efficacy
for metastatic and progressive multi-irradiated thyroid cancer. In this clinical
prospective study, 11 patients (mean age +/- 1 SD = 61 +/- 12 years, sex ratio
M/F = 5/6) with a progressive disease despite iterative surgery and iodine
irradiations were treated with 13-cis-retinoic acid (1.5 mg/kg day) over 8 weeks
prior to I-131 irradiation. The redifferentiating effect of RA was evaluated by
serum thyroglobulin (Tg) monitoring during RA treatment and qualitative analysis
of iodine uptake on the post-therapeutic whole body scan. The clinical usefulness
of RA treatment was assessed by clinical follow-up, Tg monitoring, and tumor
size. No serious event that could possibly be related to the treatment was
reported. The mean follow up time was 24.2 +/- 12 months (range 3-46 months).
Iodine uptake was only slightly improved in two patients. Nevertheless, the
clinical benefits of RA seem to be very poor. Five patients died of a metastatic
disease. Five others presented new clinical evidences of a progressive disease.
In conclusion, this prospective study demonstrates the absence of efficacy of I
131 irradiation combined with RA for the treatment of patients with aggressive,
rapidly growing metastatic thyroid cancer. Thus, patients with highly aggressive
disease, rapidly growing in a short period from 2 to 6 months, should not be
considered for RA therapy.
PMID- 17042690
TI - Time trends of incidence rates of thyroid cancer in Israel: what might explain
the sharp increase.
AB - BACKGROUND: Worldwide changes in the incidence, histological type, and prognosis
of thyroid cancer (TC) have been observed. Regional differences in the spectrum
of TC may be related to genetic factors, ionizing radiation, lifestyle, and
nutritional iodine, as well as to the availability of medical services. METHODS:
Analysis of records of 5864 TC patients (diagnosed between 1982 and 2001),
retrieved from the Israel National Cancer Registry. RESULTS: The age-standardized
incidence rate (ASR per 100,000 persons) of TC among Jewish women in 2001 was
12.45 (higher than generally reported in the world) and 3.68 among Jewish men.
There was a significant increase in the ASR for TC between 1982 and 2001 in the
Jewish population (by 101% among women and by 25% among men, p < 0.01 for both),
mainly due to papillary carcinoma. TC incidence increased in the non-Jewish
population from 2.33 to 6.02 in women (p < 0.05) and from 1.13 to 2.49 in men (p
> 0.05). TC incidence was similar among immigrants from Europe and America
arriving in Israel before 1990 or after 1990 for both genders. An improved 5-year
survival was noted in patients diagnosed between 1992 and 1996 in comparison to
patients diagnosed earlier: 1982-1986 (86% versus 78%, p < 0.01). CONCLUSIONS: A
marked increase in TC incidence over the last two decades (mainly due to
papillary carcinoma) has been noted in different Israeli subpopulations, being
the highest in Jewish women. The increase trends were similar regardless of
gender or ethnicity. The reasons for this rise in TC incidence and improvement in
the survival are probably multifactorial and may relate partly to increased
diagnostic vigilance and changes in clinical practice.
PMID- 17042691
TI - Differential evolution of thyroid peroxidase and thyrotropin receptor antibodies
in Graves' disease: thyroid peroxidase antibody activity reverts to pretreatment
level after carbimazole withdrawal.
AB - In this study, we compared the evolution of thyroid peroxidase antibody (TPOAb)
and thyroid-stimulating antibody (TSAb) activities before, during, and after
treatment of Graves' disease (GD) with carbimazole. TPOAb and TSAb were measured
in sera from 75 patients with GD, during an 18-month block-replace regimen and
after drug withdrawal (12, 24, and 36 months). At diagnosis, TPOAb were present
in 85% of the patients versus 99% for TSAb. During the treatment, TPOAb values
and prevalence significantly decreased, as observed with TSAb. After drug
withdrawal, TPOAb levels increased once again to reach the pretreatment values,
whereas TSAb remained unchanged. TPOAb values and prevalence at drug withdrawal
were not significantly different between patients who remained euthyroid and
those who had a relapse of hyperthyroidism. In contrast, TSAb values and
prevalence were higher at drug withdrawal in relapse patients. In conclusion,
TPOAb and TSAb changes are similar during GD treatment by carbimazole but diverge
after drug withdrawal. TPOAb might reflect autoimmune perturbations independently
of the clinical status and of the thyroid-stimulating activity.
PMID- 17042692
TI - Impaired enteral levothyroxine absorption in hypothyroidism refractory to oral
therapy after thyroid ablation for papillary thyroid cancer: case report and
kinetic studies.
AB - We present a 49-year-old patient suffering from hypothyroidism (thyrotropin
[TSH], 20-80 mU/L) refractory to oral levothyroxine (LT(4)) substitution after
total thyroidectomy and radioiodine therapy for papillary thyroid cancer.
Extensive, repetitive work-up excluded small bowel, liver, and pancreatic disease
and drug interactions. Triiodothyronine/thyroxine (T(3)/T(4)) antibodies were
negative and reverse T(3) levels were normal. Supervised absorption tests of
several LT(4) preparations in increasing dosages (250-1500 microg/d) confirmed an
insufficient rise in serum T(4) levels following oral drug administration. Thus,
intravenous LT(4) application (5 times per week) was commenced to restore at
least normal range TSH levels. Repetition of absorption tests 1 year later, after
a documented period of more than 3 months of stable euthyroidism, showed a
considerable improvement of intestinal LT(4) uptake. Subsequently, the patient
was managed on large doses of oral LT(4) (1500-2100 microg/d) alone, but this was
found to be insufficient so that continuous intravenous LT(4) was administered
via a morphine pump device to ultimately achieve stable euthyroidism. Of note, at
4-year follow-up there was no evidence of recurrent or metastasized papillary
thyroid cancer. The reason for the disturbed intestinal LT(4) absorption in this
patient remains unresolved. However, we would like to suggest the possibility of
a specific intestinal uptake deficit, which will only become apparent in the case
of previous thyroid ablation.
PMID- 17042693
TI - Burkitt's lymphoma presenting as a rapidly growing thyroid mass.
AB - A 53-year-old man was admitted to the hospital because of tracheal compressive
symptoms from a rapidly expanding thyroid mass. The patient first noticed the
nodule less than a week prior to admission. Thyroid tests were normal. A fine
needle aspiration (FNA) biopsy showed a monotonous population of intermediate
sized lymphoid cells with scant cytoplasm suspicious for lymphoma. Twelve hours
later an emergent computed tomography (CT) scan confirmed left tracheal deviation
with compression, however, there were no signs of tumor invasion. The patient
received emergent CHOP (clophosphamide, adriamycin, vincristine, prednisone) and
rituxan therapy. His mass completely resolved within 36 hours. Bone marrow biopsy
provided the final diagnosis of stage IV Burkitt's lymphoma and his therapy was
changed to hyper CVAD-R chemotherapy (cytoxan, vincristine, adriamycin,
dexamethasone, rituxan). The patient's hospital course was complicated by tumor
lysis syndrome that was managed by hydration and allopurinol. To our knowledge,
this is only the second reported case of Burkitt's lymphoma presenting as a
thyroid mass. His presentation highlights the urgency in diagnosis and provides
an opportunity to review a rare type of primary thyroid lymphoma.
PMID- 17042694
TI - Needle tract implantation of follicular neoplasm after fine-needle aspiration
biopsy: report of a case.
AB - We herein report a 28-year-old woman with a follicular neoplasm showing
subcutaneous needle tract implantation. One month after fine-needle aspiration
biopsy (FNAB) for a tumor measuring 2.5 cm, the patient became aware of a
subcutaneous nodule measuring about 1 cm at the needle insertion site. FNAB smear
of this nodule showed poorly cohesive clusters of follicular cells with nuclear
crowding, overlapping and resetting with some microfollicular architecture. Total
thyroidectomy and resection of the subcutaneous nodule were performed. Although
there was no capsular or vascular invasion of the nodule, the lesion was
diagnosed as follicular carcinoma because of the subcutaneous seeding. Ki-67
labeling indices of the thyroid nodule and implanted tumor were higher than 5%.
Furthermore, although galectin-3 was completely negative in the thyroid nodule,
it was heterogeneously positive in the implanted tumor. It is therefore suggested
that high cell proliferating activity as a characteristic of the original nodule
and the subsequently obtained invasive characteristic of the implanted tumor
contributed to this event. To date, there has not been any recurrence of the
implanted lesion. Because implanted follicular carcinoma can be surgically
removed, this complication should not impair the usefulness of FNAB.
PMID- 17042695
TI - Coregistered iodine-131 single photon emission computed tomography/computed
tomography reveals dedifferentiation in a metastatic follicular thyroid
carcinoma.
PMID- 17042696
TI - Extraskeletal Ewing sarcoma mimicking a thyroid nodule.
PMID- 17042700
TI - Lessons learned, funded research, integrity--what does it all mean?
PMID- 17042702
TI - Telethinking: with James A. Brink, M.D. [interview by Vicki Glaser].
PMID- 17042703
TI - Cost effectiveness, safety, and satisfaction with video telepsychiatry versus
face-to-face care in ambulatory settings.
AB - Videoconference telepsychiatry provides an alternative for the psychiatric
treatment of mental health patients who reside in remote communities. The
objective of this study was to compare institutional ambulatory and
hospitalization costs, treatment adherence, patient and physician satisfaction,
and treatment safety between mental healthcare via videoconferencing and care
provided in person. Data collected for 1 year of telepsychiatry treatment was
compared to that of the preceding year and a matched comparison group. Twenty
nine patients from Or Akiva and 20 patients from Reut Hostel in Hadera who met
the inclusion criteria agreed to participate; 24 and 15 patients, respectively,
completed the study. Forty-two matched patients, who continued face-to-face
interviews, comprised the comparison group. Drop-out patients and those who did
not consent to telepsychiatry treatment were not involved. During the year of
telepsychiatry treatment, patients and physicians were satisfied and treatment
was safe. However, 1 hour of telepsychiatry treatment was more expensive than
face-to-face care, and a tendency of increased hospitalizations was noted.
Adherence ratios before and during telepsychiatry treatment were similar, but
were twice as high versus the comparison group. The limited sample size precludes
the drawing of definite conclusions, and further studies involving a larger study
population and longer duration of investigation is warranted.
PMID- 17042704
TI - The accident and emergency department virtual consulting room.
AB - The goal was to describe the development of the Virtual Consulting Room (VcR), a
unique intranet-based guidance application providing direct access to local
specialist knowledge, and to evaluate its usability and whether it has the
potential to educate staff while working in the Accident and Emergency (A&E)
department. Duty staff of the A&E Department, The Royal Free Hospital, London,
participated in a prospective observational study. Two hundred and twenty
consecutive patients were identified from the triage section of their casualty
card as having a presenting complaint that featured in the VcR. These casualty
cards were highlighted with a red sticker alert and a short questionnaire
attached. Members of staff were invited to consult with the VcR after assessing
each patient by clicking on an icon located on the department's computer
desktops. No prior training was provided. The questionnaire was completed in 103
of 220 (46.8%) patients. The VcR was used in the management of 38 of 220 (17.3%)
patients. In 21 of 38 (55.3%), users reported the VcR supported clinical decision
making, in 20 of 38 (52.6%) the VcR improved knowledge and in 11 of 38 (28.9%)
the VcR helped directly influence the decision to discharge the patient. In 2 of
38 (5.3%) users changed their decision to refer and in 1 of 38 (2.6%)
investigations were altered. This evaluation indicates that A&E clinicians
accessing the VcR found it easy to use and educational in the workplace.
PMID- 17042705
TI - Teleconsultation for cardiac patients: a comparison between nurses and
physicians: the SHL experience in Israel.
AB - The absence of randomized studies on sufficiently large patient cohorts precludes
the drawing of any firm conclusions on the comparative performance between nurses
and physicians in transtelephonic triage and consultations and in diagnostic and
management decision-making. We conducted such a comparative study at the SHL
telemedicine facility. This facility also provides face-to-face medical
management for its subscribers by means of mobile intensive care units (MICUs)
staffed by physicians. The outcome of calls that came between 7:00 AM and 11:00
PM throughout the study year and that were handled at random by specially trained
physicians (n = 15) or nurses (n = 35) were analyzed. Of 48,707 subscribers who
fulfilled the study entry criteria 25,106 used the service at least once,
producing 88,103 calls (81,817 handled by nurses and 6,286 by physicians).
Teleconsultations were sufficient for most of the cases (80.13%). There were no
significant differences between the performance of nurses and physicians
regarding demographics (age, gender) and medical diagnoses of the applicants. The
nurses' performance and decisions were comparable to those of physicians with
respect to teleconsultations, medically justified dispatches of an MICU, repeated
calls to the center and mortality during the week after the index call, although
the duration of the physicians' telephone consultations was longer. Delegation of
equal authority to nurses and physicians in triage and consultation in
telecardiology results in equivalent and highly satisfactory medical care in a
system in which subscribers receive service orchestrated from a single center of
telecommunications.
PMID- 17042706
TI - Eye contact in medical examinations using videophones.
AB - In Japan, approximately 12,000,000 cellular phones with a videophone function
have been distributed and are becoming an important part of the telemedicine
infrastructure. By eye movement analysis, we investigated the effectiveness of
eye contact using cellular videophones during medical interviews. Three male
volunteers acted as first-time patients and were filmed using a high-resolution
camera. The video of each of these volunteers was converted into pictures of
three different sizes-70 cm x 40 cm (large picture), 26 cm x 20 cm (medium
picture), and 14 cm x 12 cm (small picture)-and viewed on a 32-inch video
monitor. The large, medium, and small pictures were considered to represent an
actual medical interview, an interview via a television conference system, and an
interview via a cellular videophone, respectively. Nine doctors watched these
pictures, and their eye movements were recorded with a gaze-point recorder. After
watching the videos, the doctors evaluated quality of three size pictures.
Standard deviation values of the gaze point coordinates decreased with the
picture size. However, a very low decrease was observed in the time ratio, during
which the gaze point was on the face (eye contact rate); the rate was 92.2%
(large picture), 91.8% (medium picture), and 85.1% (small picture). No
statistical difference was observed between the values of the medium and small
pictures. Subjective evaluations yielded low scores in the small pictures. The
relatively high rate of eye contact rate in the small pictures suggests that a
cellular videophone will be a good tool for telemedicine, although the usage by
which the subjective evaluations can be improved should be determined by doctors.
PMID- 17042707
TI - Osteosarcoma: evaluation of information on the internet.
AB - The information about osteosarcoma on the existing websites was examined. The
purpose of this study was to evaluate the quality of Internet information
available to patients on the topic of osteosarcoma. The secondary purpose was to
rank the identified websites with respect to the caliber of relevant information
provided by the websites sponsors' identity. A great many of people in the world
"surf" the World Wide Web, searching for medical information. The information on
the Internet varies dramatically in terms of content and quality for lack of
uniformed standard with respect to the medical publications on the Internet. Five
search engines searched the search terms "osteosarcoma." The first 25 links
displayed by each engine were evaluated for a theoretical total of 125 websites.
According to the information context, sponsor identity we evaluated each website.
An information quality score of 0 to 26 was generated for each site. A score of
20 or greater was thought to be "high-quality" information website. Eighty-nine
unique websites were identified, among which only 8 (9%) scored 20 or more on the
information quality score; 32 scored 10 or less. The overall mean information
quality score was 11.5. The websites with highest mean scores were academic
organization and affiliated hospitals of university. The quality of Internet
information on osteosarcoma is variable. Less than 10% of relevant websites were
of high information value. The rank list of high quality websites from our
information quality score should provide useful information of osteosarcoma.
PMID- 17042708
TI - Psychiatrists' satisfaction with telepsychiatry.
AB - The purpose of this evaluation study was to learn more about psychiatrists'
satisfaction with telepsychiatry. Telepsychiatry will succeed only if
psychiatrists are satisfied with this service delivery method and offer it to
their patients. While telepsychiatry appears to be effective and most patients
report that they are satisfied with it, less information is available about
factors that lead to psychiatrists' satisfaction. We interviewed psychiatrists
who treat rural/frontier patients and asked them to describe factors that
encouraged or discouraged their use of telepsychiatry. Only 4 were mostly
satisfied with telepsychiatry and all offered suggestions for improving this
delivery method. Most agreed that it was a hardship for many of their patients to
travel 100 to 750 roundtrip miles over a 1-3 day period for a 20-minute
consultation and that telepsychiatry could be a lifeline to many of them.
Nevertheless, they identified significant technical and interpersonal barriers
that discouraged their use of telepsychiatry.
PMID- 17042709
TI - Development of a broadband telehealth system for critical care: process and
lessons learned.
AB - A broadband telehealth system has been developed for supporting critical care
services between a major referral hospital and a rural hospital by transmitting
very high-quality, realtime multimedia information, including images, audio and
real-time video, over an Internet Protocol (IP)-based network. The technical
design team took an iterative and user-centred approach toward the system design.
Usability tests with scenario analysis were incorporated into the development
process to produce a system that operates seamlessly in the critical care
environment. Careful analysis of the reliability of the system was incorporated
into the clinical protocols for integration into existing work practices. The use
of high-quality multimedia data, consideration of human factors early in the
design process, and incorporation of proper development approaches were critical
for the success of the system design.
PMID- 17042710
TI - Group tele-exercise for improving balance in elders.
AB - This study was to assess the level of acceptance and efficacy of a group tele
exercise program designed for balance impaired elders to improve balance and
reduce fear of falling. The program would allow a group of elderly subjects to
participate in a structured, interactive, and supervised exercise class from
their own homes through a videoconferencing system. A total of 17 independent
living elderly subjects (mean age, 81 +/- 8 years) participated in the study. An
Internet-based videoconferencing device (VCD) was installed in each subject's
home, allowing real-time video and audio communication with the exercise
instructor and all other participants. The exercise was in the form of Tai Chi
Quan, three times per week for 15 weeks. The main study measures included
exercise compliance, level of acceptance and satisfaction, and the effectiveness
of the exercise program on balance, fear of falling, and general health. Three
subjects dropped out of the study. For those remaining, the average compliance
was 78% (range, 51% to 98%). All subjects were able to operate the VCD
independently, and expressed earnest interest in continuing tele-exercise
programs in the future. There were significant improvement (p < 0.05)
postexercise in fear of falling score (18%), single leg stance time (43%), Up-and
Go time (21%), and body sway during quiet stance (>8%). This study has
demonstrated that the group tele-exercise program is acceptable and welcomed by
elders, and is effective for improving balance and reducing fear of falling.
PMID- 17042711
TI - Patient satisfaction levels during teleophthalmology consultation in rural South
India.
AB - The application of new technologies for analysis of retinal images, neural
networks for automated retinopathy grading, and teleophthalmology have been shown
to have great value in ophthalmology. India has only one ophthalmic surgeon for
every 107,000 population. Given this situation, teleophthalmology can play a
vital role in addressing to the eye care needs of the country. The objective of
this study was to assess patient satisfaction levels and factors influencing it
during teleophthalmology consultation in India. A patient satisfaction
questionnaire was prepared to assess the prominent aspects of patient
satisfaction, including teleophthalmology screening, confidence in the technology
used to transfer the fundus images, comprehensiveness of information available to
the doctor in the central hub, and graded the opinion regarding the
teleophthalmology. A cross-sectional survey among patients who attended a
teleophthalmology screening conducted across eight villages in rural Tamilnadu.
Responses were then subjected to qualitative analysis and conclusions made. The
number of respondents was 348. Of this, 56.4% were males. The mean age of was 50
+/- 17 years. Age ranged from 2 years to 83 years. 44.4% of the respondents were
satisfied with teleophthalmology screening. (95% confidence interval [CI]: 38.58%
49.42%) No association was found between age, gender, education, and occupation,
respectively, with satisfaction levels. We found that patients who asked
questions during the screening were 2.18 times more likely to be satisfied with
teleophthalmology than those who did not (odds ratio [OR] = 2.19, 95% CI 1.37
3.5). This study highlights sentiments of the rural subjects when they underwent
teleophthalmology consultations. This study provides valuable insights about
patient's preferences and satisfaction levels with this newer technology.
PMID- 17042712
TI - Research recommendations for the american telemedicine association.
AB - The American Telemedicine Association (ATA) convened a panel of experts to
generate a research agenda for the telemedicine community to further support and
promote the long-term acceptance and use of telehealth. Three principles to guide
research and four key areas within which research is greatly needed were
identified. These four areas are technical, clinical, human factors and
ergonomics, and economic analyses. It is the hope of the panel that the research
recommendations put forth in this document will give investigators the
inspiration, tools and goals to make this happen.
PMID- 17042713
TI - Evolution of telemedicine from an applied communication perspective in the United
States.
AB - Telemedicine, the use of telecommunication technologies to provide health
services over some distance, has a history that spans more than five decades.
Technological development and deployment have been interrelated with shifting
paradigmatic views. This paper proposes that telemedicine has evolved through
three generations that began with telemedicine as a communication medium to
complement traditional services to a technology of automation and decision tools
that expands the scope and range of health services and creates a unique health
communication context. This paper provides a literature review and overviews
three proposed evolutionary stages for telemedicine to date, namely synchronous
versus asynchronous modalities, data transfer and storage, and automating
decision making and robotics. Finally, we conclude with a discussion of the
barriers for telemedicine and a call for engineers to join with social scientists
and medical professionals to set an agenda for future telemedicine development.
PMID- 17042714
TI - Recruitment and enrollment of rural and urban medically underserved elderly into
a randomized trial of telemedicine case management for diabetes care.
AB - Our goal was to identify reasons for enrollment or refusal to participate in a
randomized trial of telemedicine case management of diabetes. We performed a
prospective survey of participants and non-participants during recruitment for
the Informatics for Diabetes Education and Telemedicine (IDEATel) study, a
randomized trial of telemedicine case management of diabetes mellitus in
medically underserved elderly. There were two recruitment areas: urban New York
City, and rural upstate New York. A Participant Questionnaire (PQ) was
administered at the baseline IDEATel visit, and a Non-Participant Questionnaire
(NPQ) was administered during the recruitment telephone call. Both questionnaires
listed possible responses; subjects could choose more than one response or give
their own. Of 1,660 IDEATel participants, 99.7% completed the PQ. Most frequent
reason for participation was the belief that the technology could help them (52%
and 42% of urban and rural respondents, respectively). Of the 2,231 subjects
refusing participation, 28% answered the NPQ (90% of respondents were from rural
area). Most frequent reasons not to participate in the rural area were being too
busy (23%), and discomfort with the technology (22%), and in the urban area the
belief that the technology could not help them (71%), discomfort with it (52%),
and not liking to participate in studies (52%). In multivariate analysis (rural
respondents only), knowing how to use a computer was an independent predictor of
participation (p < 0.001). In conclusion, perceptions and beliefs regarding
technology, including the expectation to benefit from it, played an important
role in the decision to participate.
PMID- 17042715
TI - Dose-response effects of intermittent PTH on cancellous bone in hindlimb unloaded
rats.
AB - HLU suppressed bone formation and resulted in bone loss in the tibial metaphysis
of 6-month-old male rats. A human therapeutic dose of intermittent PTH (1
microg/kg/day) prevented the skeletal changes associated with HLU. INTRODUCTION:
Skeletal unloading of skeletally mature rats results in trabecular thinning in
the proximal tibial metaphysis, which is in part caused by a decrease in bone
formation. We examined the efficacy of PTH in preventing the detrimental skeletal
effects that occur with hindlimb unloading (HLU). MATERIALS AND METHODS: Six
month-old male Fisher 344 rats were HLU and treated with vehicle or recombinant
human PTH(1-34) at 1, 5, 20, or 80 microg/kg/day for 2 weeks. The bone response
was measured by microCT analysis of bone structure, histomorphometric analysis of
static and dynamic bone parameters, and Northern blot analysis of mRNA levels for
bone matrix proteins. The PTH-treated HLU animals were compared with vehicle
treated HLU and pair-fed normal weight-bearing controls. RESULTS: Unloading
resulted in a decrease in cancellous bone volume that was caused in part by a
dramatic 83% decrease in bone formation. All dose rates (1-80 microg/kg/day) of
human PTH(1-34) significantly increased bone formation rates compared with
vehicle-treated HLU controls. There was a dose response, and the highest dose
rate of the hormone increased bone formation compared with normal weight-bearing
rats by 708% (p < 0.0001). The increases in bone formation were accompanied by
increases in mRNA levels for type 1 collagen, osteocalcin, and osteonectin. Also,
treatment with PTH resulted in increases in mineral apposition rate and double
labeled perimeter, but the latter was disproportionally increased at high dose
rates. A therapeutic dose of PTH (1 microg/kg/day) prevented disuse-induced
trabecular thinning, whereas high-dose PTH (80 microg/kg/day) increased
trabecular thickness compared with normal weight-bearing rats. CONCLUSIONS: These
findings reveal that administration of a therapeutic dose of PTH to HLU rats
prevents the decrease in bone formation and trabecular thinning, whereas high
dose rates of the hormone increase bone formation and trabecular thickness to
values that exceed normal values.
PMID- 17042717
TI - Clodronate reduces the incidence of fractures in community-dwelling elderly women
unselected for osteoporosis: results of a double-blind, placebo-controlled
randomized study.
AB - A 3-year prospective, randomized, placebo-controlled trial of oral clodronate 800
mg showed that the incidence of clinical fractures was decreased by 20% in 5596
elderly women unselected for osteoporosis. The effect occurred in the absence of
systematic calcium and vitamin D supplementation and was observed across a wide
range of BMDs. INTRODUCTION: To date, most studies with bisphosphonates have
reported on their use in individuals selected to be at high risk for fracture
usually by the presence of low BMD or a prior fragility fracture, usually of the
spine. We wished to determine the effect of the bisphosphonate, clodronate, on
the rate of fractures in women > or =75 years of age living in the community.
MATERIALS AND METHODS: Women > or =75 years of age living in the general
community in South Yorkshire and North Derbyshire, identified from general
practice registers, were recruited by letter of invitation to a randomized,
double-blind, controlled trial of 800 mg oral clodronate (Bonefos) or matching
placebo daily over 3 years. The main outcomes were the incidences of hip and any
clinical fracture. RESULTS: Of the 5579 elderly women included in the intention
to-treat analysis of efficacy, 114 had a new hip fracture during the 3-year
treatment phase: 56 (2.0%) women in the clodronate group and 58 (2.1%) women in
the placebo group (hazard ration [HR], 1.02; 95% CI, 0.71-1.47). Clodronate did,
however, decrease the incidence of any clinical fracture by 20% (264 women [9.5%]
versus 337 [12.1%] in the placebo group; HR, 0.80; 95% CI, 0.68-0.94). The
incidence of osteoporosis-associated nonhip fractures was also significantly
decreased by 29% (5.2% versus 7.4%; HR, 0.71; 95% CI, 0.57-0.87). The ability of
clodronate to reduce the risk of osteoporotic fracture was independent of
baseline BMD, but the number needed-to-treat was lower in the presence of
osteoporosis. CONCLUSIONS: Oral daily clodronate can prevent fractures without
significant adverse effects in elderly women living in the general community. The
effect on hip fracture risk is not significant, but an effect similar to that at
other nonvertebral sites cannot be excluded. This study suggests that
antiresorptive therapies can reduce fracture incidence in high-risk individuals
even in the presence of a normal or osteopenic BMD.
PMID- 17042716
TI - RGS12 is essential for RANKL-evoked signaling for terminal differentiation of
osteoclasts in vitro.
AB - How RANKL evokes [Ca(2+)](i) oscillations and leads to osteoclast differentiation
is unclear. We identified a new signaling protein, RGS12, and found that RGS12 is
essential for [Ca(2+)](i) oscillations and osteoclast differentiation induced by
RANKL. RGS12 may play a critical role in the RANKL-evoked PLCgamma-calcium
channels-[Ca(2+)](i) oscillation-NFAT2 pathway. INTRODUCTION: RANKL-induced
[Ca(2+)](i) oscillations play a switch-on role in NFAT2 expression and osteoclast
differentiation. However, RANKL evokes [Ca(2+)](i) oscillations and leads to
osteoclast differentiation by an unknown mechanism. In this study, we identified
a new RANKL-induced signaling protein, regulator of G signaling protein 12
(RGS12), and investigated its effect on osteoclast differentiation in vitro.
MATERIALS AND METHODS: We used a genome-wide screening approach to identify genes
that are specifically or prominently expressed in osteoclasts. To study the role
of the RGS12 in osteoclast differentiation, we used vector and lentivirus-based
RNAi gene silencing technology to silence the RGS12 gene in the monocyte
progenitor cell lines and primary bone marrow-derived monocytes (BMMs). The
interaction between RGS12 and N-type calcium channels was elucidated using co
immunoprecipitation and immunoblotting. RESULTS: We found that RGS12 was
prominently expressed in osteoclast-like cells (OLCs) induced by RANKL. This
result was further confirmed at both the mRNA and protein level in human
osteoclasts and mouse OLCs. Silence of RGS12 expression using vector and
lentivirus based RNA interference (RNAi) impaired phosphorylation of
phospholipase C (PLC)gamma and blocked [Ca(2+)](i) oscillations, NFAT2
expression, and osteoclast differentiation in RANKL-induced RAW264.7 cells and
BMMs. We further found that N-type calcium channels were expressed in OLCs after
RANKL stimulation and that RGS12 directly interacted with the N-type calcium
channels. CONCLUSIONS: These results reveal that RGS12 is essential for the
terminal differentiation of osteoclasts induced by RANKL. It is possible that
RGS12 regulates osteoclast differentiation through a PLC gamma-calcium channel
[Ca(2+)](i) oscillation-NFAT2 pathway.
PMID- 17042719
TI - Horse slaughter ban clears House.
PMID- 17042720
TI - Echoes the desire for comparative medicine.
PMID- 17042721
TI - A proposal for the assessment of the quality of food supply veterinary medical
education.
PMID- 17042722
TI - What is your diagnosis? Inflammatory epithelium and ceruminous gland
adenocarcinoma.
PMID- 17042723
TI - What is your diagnosis? Disorder of the swim bladder.
PMID- 17042725
TI - Animal behavior case of the month.
PMID- 17042724
TI - Anesthesia case of the month. Hypotension.
PMID- 17042726
TI - Employment of female and male graduates of US veterinary medical colleges, 2006.
PMID- 17042727
TI - Detection of Borrelia burgdorferi DNA in tissues from dogs with presumptive Lyme
borreliosis.
AB - OBJECTIVE: To develop a quantitative PCR assay for detection of Borrelia
burgdorferi DNA in formalin-fixed, paraffin-embedded tissues; compare results of
this assay with results of immunohistochemical staining of tissues from
seropositive dogs; and determine whether B burgdorferi DNA could be detected in
renal tissues from dogs with presumptive Lyme nephritis. DESIGN: Cohort study.
SAMPLE POPULATION: Archived tissue samples from 58 dogs. PROCEDURES: A
quantitative PCR assay was performed on formalin-fixed, paraffin-embedded tissue
sections from the dogs. Results were compared with results of immunohistochemical
staining, B burgdorferi serostatus, clinical signs, and necropsy findings.
RESULTS: 38 dogs were classified as having positive or equivocal results for Lyme
borreliosis, and 20 were classified as having negative results on the basis of
clinical signs, serologic findings, and pathologic abnormalities. Borrelia
burgdorferi DNA was amplified from tissue samples from only 4 (7%) dogs, all of
which had been classified as having positive or equivocal results for Lyme
borreliosis and had signs of presumptive Lyme nephritis. Results of PCR assays of
renal tissue were positive for only 1 dog, and there was no agreement between
results of immunohistochemical staining (ie, detection of B burgdorferi antigen)
and results of the PCR assay (ie, detection of B burgdorferi DNA) for renal
tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that detection of
B burgdorferi DNA in formalin-fixed, paraffin-embedded tissues is feasible, but
that intact B burgdorferi DNA is rarely found in tissues from naturally infected
dogs, even tissues from dogs with presumptive Lyme borreliosis. Further, findings
support the contention that Lyme nephritis may be a sterile, immune complex
disease.
PMID- 17042728
TI - Toxicosis associated with ingestion of quick-dissolve granulated chlorine in a
dog.
AB - CASE DESCRIPTION: A dog was referred for treatment after ingestion of quick
dissolve chlorine granules intended for use in a swimming pool. CLINICAL
FINDINGS: At evaluation 18 hours after ingestion of the granules, the dog had
tachypnea, signs of depression, approximately 5% dehydration, oral mucositis, and
a productive cough. Increased respiratory tract sounds and wheezes were ausculted
in all lung fields. Complete blood count revealed erythrocytosis and lymphopenia.
Serum biochemical analyses revealed mildly high activities of hepatic enzymes and
creatine kinase. Arterial blood gas concentrations were consistent with hypoxemia
and hyperventilation. Thoracic radiography revealed widespread pulmonary alveolar
infiltrates predominantly affecting the ventral portions of both lungs,
consistent with noncardiogenic pulmonary edema secondary to aspiration of the
granulated chlorine. TREATMENT AND OUTCOME: Initial treatment included IV
administration of an electrolyte solution with supplemental KCl, ranitidine,
furosemide, cefotaxime, buprenorphine, and supplemental oxygen. Subsequent
treatment included administration of meloxicam and an endoscopically placed
percutaneous gastrostomy tube. Endoscopic examination revealed esophagitis and
mild gastritis; therefore, metoclopramide and sucralfate were also administered.
Fifteen days later, the gastrostomy tube was removed prior to discharge;
endoscopic examination revealed grossly normal esophageal and gastric mucosa, and
thoracic radiography revealed complete resolution of the lung lesions. CLINICAL
RELEVANCE: Although ingestion of granulated chlorine is rare in veterinary
patients, the resulting disease processes are common and can be treated
successfully.
PMID- 17042730
TI - Evaluation of risk factors for development of secondary glaucoma in dogs: 156
cases (1999-2004).
AB - OBJECTIVE: To determine the immediately antecedent cause of secondary glaucoma
and the prevalence of secondary glaucoma with anterior uveitis or lens
dislocation in dogs. DESIGN: Retrospective case series. ANIMALS: 156 dogs with
secondary glaucoma. PROCEDURES: Cause of glaucoma was determined from records.
Breed, age, sex, and neuter status of all dogs with secondary glaucoma were
compared with the general hospital population. The prevalence of secondary
glaucoma in dogs with a primary diagnosis of lens dislocation or anterior uveitis
during the same period was determined. RESULTS: Secondary glaucoma was diagnosed
in 156 of 2,257 (6.9%) dogs examined because of ophthalmic disease and was
bilateral in 33 (21.2%) of those dogs. In 31 (94%) bilaterally affected dogs, the
antecedent cause was the same in both eyes. Common causes of secondary glaucoma
were non-surgical anterior uveitis (44.9%), anterior uveitis associated with
prior phacoemulsification (15.8%), and lens dislocation (15.2%). Parson Russell
Terriers, Poodles, Boston Terriers, Cocker Spaniels, Rhodesian Ridgebacks, and
Australian Cattle Dogs had diagnoses of secondary glaucoma more often than
expected, compared with the reference population. Age, sex, neuter status, and
laterality were not associated with secondary glaucoma. The prevalence of
secondary glaucoma in dogs with lens dislocation or uveitis was 15% or 17%,
respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Glaucoma develops secondary to
many intraocular diseases, particularly uveitis and lens dislocation. Diagnosis
of these diseases should prompt frequent monitoring of intraocular pressure,
regardless of signalment.
PMID- 17042731
TI - Effect of rostrocaudal mobility of the mandible on feed digestibility and fecal
particle size in horses.
AB - OBJECTIVE: To evaluate the effect of rostrocaudal mobility (RCM) of the mandible
during extension and flexion of the atlanto-occipital joint on weight gain, feed
digestibility, and fecal particle size in horses. DESIGN: Randomized controlled
trial. ANIMALS: 34 pregnant mares housed in 1 barn. PROCEDURES: Horses were
randomized into a treatment (n = 17) or control (17) group. All horses were
sedated, and the distance between the rostral portions of the upper and lower
incisor arcades was determined during extension and flexion of the atlanto
occipital joint; mandibular RCM was calculated as the difference between these
values. In the treatment group, measurements were made after dental floating.
Body weight was recorded 1 day before dental floating and at intervals after
mandibular RCM determination for a period of 24 weeks. Feces were collected from
each horse during two 5-day periods. Samples of feed and feces were analyzed to
determine feed digestibility; particle size analysis was performed on dried fecal
samples. RESULTS: Data obtained from each group of horses revealed that RCM of
the mandible did not affect weight gain, feed digestibility, or particle size in
feces; there were no differences among breeds. Controlling for age and number of
dental lesions did not significantly affect results. CONCLUSIONS AND CLINICAL
RELEVANCE: In horses, RCM of the mandible did not appear to affect weight gain,
feed digestibility, or fecal particle size. On the basis of these and other
published data, the assumption that dental abnormalities affect digestion
detrimentally in horses needs to be reevaluated.
PMID- 17042733
TI - Antimicrobial susceptibility patterns of respiratory tract pathogens from sheep
and goats.
AB - OBJECTIVE: To determine the antimicrobial susceptibility of common respiratory
tract pathogens from sheep and goats. DESIGN: Cross-sectional study. SAMPLE
POPULATION: 41 respiratory tract isolates from sheep and 36 isolates from goats.
PROCEDURES: Disk diffusion assay was used to determine antimicrobial
susceptibility of isolates to amoxicillin-clavulanic acid, ceftiofur,
ciprofloxacin, florfenicol, and tetracycline. Minimum inhibitory concentrations
of florfenicol for these isolates were determined by use of the microbroth
dilution technique. RESULTS: The most common isolates were Pasteurella multocida
(n = 28) and Mannheimia haemolytica (39). All isolates were susceptible to
amoxicillin-clavulanic acid, ceftiofur, ciprofloxacin, and florfenicol. Five
percent (4/77) of isolates were resistant to tetracycline. CONCLUSIONS AND
CLINICAL RELEVANCE: Susceptibility of respiratory tract pathogens isolated from
sheep and goats to commonly used antimicrobial drugs in this study was high.
Treatment of these species for bacterial respiratory tract disease is likely not
complicated by antimicrobial resistance.
PMID- 17042734
TI - Serum IgG and total protein concentrations in dairy calves fed two colostrum
replacement products.
AB - OBJECTIVE: To evaluate effects of 2 commercially available colostrum replacement
products on serum IgG and total protein concentrations in dairy calves. DESIGN:
Prospective clinical trial. ANIMALS: 84 Holstein bull calves from a single dairy.
PROCEDURES: Calves were randomly assigned to be given 4 quarts of colostrum
(group 1; n = 21), 2 packages of a colostrum replacement product (product A;
group 2; 21), 1 package of a different colostrum replacement product (product B;
group 3; 21), or 2 packages of product B (group 4; 21). Treatments were given
within 3 hours after birth, and blood samples were collected 24 hours later and
submitted for determination of serum total protein and IgG concentrations.
RESULTS: Group 1 calves had significantly higher serum total protein and IgG
concentrations than did calves in the other 3 groups. However, the percentage of
calves with adequate passive transfer (ie, serum IgG concentration > 1,000 mg/dL)
was not significantly different among groups 1 (90%), 3 (81%), and 4 (95%). In
contrast, only 10% of calves in group 2 had adequate passive transfer. It was
predicted that calves fed product B that had serum total protein concentrations >
5.2 g/dL would have serum IgG concentrations > 1,000 mg/dL at least 90% of the
time. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that product B could
be considered as an alternative to colostrum in dairy calves, but product A
failed to routinely provide adequate serum IgG concentrations when fed according
to label directions.
PMID- 17042735
TI - The multiple roles of osteoclasts in host defense: bone remodeling and
hematopoietic stem cell mobilization.
AB - Bone remodeling by bone-forming osteoblasts and bone-resorbing osteoclasts
dynamically alters the bone inner wall and the endosteum region, which harbors
osteoblastic niches for hematopoietic stem cells. Investigators have recently
elucidated mechanisms of recruitment and mobilization; these mechanisms consist
of stress signals that drive migration of leukocytes and progenitor cells from
the bone marrow reservoir to the circulation and drive their homing to injured
tissues as part of host defense and repair. The physical bone marrow vasculature
barrier that is crossed by mobilized cells actively transmits chemotactic signals
between the blood and the bone marrow, facilitating organ communication and cell
trafficking. Osteoclasts play a dual role in regulation of bone resorption and
homeostatic release or stress-induced mobilization of hematopoietic
stem/progenitor cells. In this review, we discuss the orchestrated interplay
between bone remodeling, the immune system, and the endosteal stem cell niches in
the context of stem cell proliferation and migration during homeostasis, which
are accelerated during alarm situations.
PMID- 17042736
TI - High dietary phosphate intake reduces bone strength in the growing rat skeleton.
AB - Nutrition influences peak bone mass development in early adulthood. The effect of
high dietary phosphate intake on the growing skeleton of 1-month-old male rats (n
= 30) was assessed in an 8-week intervention. High dietary phosphate intake
increased bone remodeling and impaired bone material properties, diminishing bone
mechanical strength. INTRODUCTION: High dietary phosphate intake is typical in
the Western diet. Abundant phosphate intake enhances parathyroid secretion and
bone metabolism. To study the influence of high dietary phosphate intake on
growing bone homeostasis and structure, we submitted growing rats to experimental
diets that varied in their phosphate content. MATERIALS AND METHODS: One-month
old intact male rats (n = 30) were fed a control diet (Ca:P 1:1) or an
experimental diet of either Ca:P 1:2 or Ca:P 1:3 for 8 weeks. At the beginning
and the end of the study period, the right femurs were measured using DXA. Double
labeling with tetracycline injection was performed 12 and 2 days before death.
After death, hind legs were cut loose. Left femurs were processed for
histomorphometry. Right femurs were measured with pQCT. Mechanical testing was
performed on the right femoral neck and tibial shaft. Six right tibias were
analyzed with microCT. Serum PTH, calcium, and phosphate contents were analyzed.
RESULTS: High-phosphate intake impaired growth of the animal, limited bone
longitudinal growth, and restricted femur BMC and BMD build-up. Osteoclast
number, osteoblast perimeter, and mineral apposition rate were increased, and
trabecular area and width were decreased. Phosphate decreased femur midshaft
total bone BMD, cortical bone BMD, and mean cortical thickness. High-phosphate
diet reduced femoral neck and tibial shaft ultimate strength and tibia stiffness
and toughness. In addition, serum PTH increased. CONCLUSIONS: High dietary
phosphate intake reduced growth, skeletal material, and structural properties and
decreased bone strength in growing male rats. Adequate calcium could not overcome
this.
PMID- 17042737
TI - Effects of child- and adolescent-onset endogenous Cushing syndrome on bone mass,
body composition, and growth: a 7-year prospective study into young adulthood.
AB - The long-term effects on bone and fat mass in children with endogenous CS are
unknown. In 14 children followed for 3-7 years into young adulthood after cure of
CS, whereas bone mass largely recovered, persisting increases in total body and
visceral fat suggests an increase risk of the metabolic syndrome. INTRODUCTION:
Endogenous Cushing syndrome (CS) is associated with decreased bone mass and
increased central fat mass. Whereas bone mass seems to improve after successful
treatment, little is known about whether central fat persists. MATERIALS AND
METHODS: This was a prospective study of 14 children (10 girls and 4 boys) and
adolescents with CS who were successfully treated and remained eucortisolemic.
Growth, puberty, bone mass, and body composition were evaluated at baseline and
during regular follow-up for 3 years and in seven children for a further 4 years
of remission to assess final adult height (FH), BMI, bone mass, and body
composition. RESULTS: CS compromised growth, leading to about a -0.8 SD loss of
FH and 0.9 SD increase in weight and BMI. BMD apparent density (BMAD) SD Score
(SDS) at the lumbar spine (LS) at diagnosis were -1.8 and -1.25, respectively,
and after 3 years of follow-up approached the mean with no further increase
apparent up to 7 years of follow-up. Whereas hip BMD SDS increased from -1.3 at
diagnosis to -0.40 at 3 years and 0 at 7 years of follow-up, femoral neck BMAD
remained at or around 0 SDS at diagnosis and during follow-up. BMI was >25
kg/m(2) in five of seven adult subjects, most of whom were women. Total body fat
and the ratio of visceral to subcutaneous was abnormally high in the majority of
these subjects, whereas LS volumetric BMD was -0.7 SDS. CONCLUSIONS: Despite
remission of CS, children and adolescents have significant alterations in body
composition that result in a small but significant decrease in bone mass and
increase in visceral adiposity. Although bone mass largely recovers after
endogenous CS, changes in total and visceral fat suggest these subjects are at
increased risk of the metabolic syndrome. Therefore, long-term monitoring of body
fat and bone mass is mandatory after treatment of CS.
PMID- 17042738
TI - Effects of teriparatide and alendronate on vertebral strength as assessed by
finite element modeling of QCT scans in women with osteoporosis.
AB - FE modeling was used to estimate the biomechanical effects of teriparatide and
alendronate on lumbar vertebrae. Both treatments enhanced predicted vertebral
strength by increasing average density. This effect was more pronounced for
teriparatide, which further increased predicted vertebral strength by altering
the distribution of density within the vertebra, preferentially increasing the
strength of the trabecular compartment. INTRODUCTION: Teriparatide 20 microg/day
(TPTD) and alendronate 10 mg/day (ALN) increase areal, measured by DXA, and
volumetric, measured by QCT, lumbar spine BMD through opposite effects on bone
remodeling. Using finite element (FE) modeling of QCT scans, we sought to compare
the vertebral strength characteristics in TPTD- and ALN-treated patients.
MATERIALS AND METHODS: A subset of patients (N = 28 TPTD; N = 25 ALN) from the
Forteo Alendronate Comparator Trial who had QCT scans of the spine at baseline
and postbaseline were analyzed. The QCT scans were analyzed for compressive
strength of the L(3) vertebra using FE modeling. In addition, using controlled
parameter studies of the FE models, the effects of changes in density, density
distribution, and geometry on strength were calculated, a strength:density ratio
was determined, and a response to bending was also quantified. RESULTS: Both
treatments had positive effects on predicted vertebral strength characteristics.
At least 75% of the patients in each treatment group had increased strength of
the vertebra at 6 months compared with baseline. Patients in both treatment
groups had increased average volumetric density and increased strength in the
trabecular bone, but the median percentage increases for these parameters were 5-
to 12-fold greater for TPTD. Larger increases in the strength:density ratio were
also observed for TPTD, and these were primarily attributed to preferential
increases in trabecular strength. CONCLUSIONS: These results provide new insight
into the effects of these treatments on estimated biomechanical properties of the
vertebra. Both treatments positively affected predicted vertebral strength
through their effects on average BMD, but the magnitudes of the effects were
quite different. Teriparatide also affected vertebral strength by altering the
distribution of density within the vertebra, so that overall, teriparatide had a
5-fold greater percentage increase in the strength:density ratio.
PMID- 17042739
TI - Craniosynostosis-associated gene nell-1 is regulated by runx2.
AB - We studied the transcriptional regulation of NELL-1, a craniosynostosis-related
gene. We identitifed three OSE2 elements in the NELL-1 promoter that are directly
bound and transactivated by Runx2. Forced expression of Runx2 induces NELL-1
expression in rat calvarial cells. INTRODUCTION: We previously reported the
upregulation of NELL-1 in human craniosynostosis and the overexpression of Nell-1
in transgenic animals that induced premature suture closure associated with
increased osteoblast differentiation. To study the transcriptional regulation of
NELL-1, we analyzed the 5' flanking region of the human NELL-1 gene. We
identified three osteoblast specific binding elements 2 (OSE2) sites (A, B, and
C) within 2.2 kb upstream of the transcription start site and further studied the
functionality of these sites. MATERIALS AND METHODS: An area of 2.2 kb and a
truncated 325 bp, which lacked the three OSE sites, were cloned into a luciferase
reporter gene, and co-transfected with Runx2 expression plasmid. The three OSE2
sites were individually mutated and co-transfected with Runx2 expression plasmid
into Saos2 cells. Gel shifts and supershifts with Runx2 antibodies were used to
determine specific binding to OSE2 sites. CHIP assays were used to study in vivo
binding of Runx2 to the Nell-1 promoter. Runx2 expression plasmid was transfected
into wildtype and Runx2(-/-) calvarial cells. Nell-1, osteocalcin, and Runx2
expression levels were measured using RT-PCR. RESULTS: Addition of Runx2 dose
dependently increased the luciferase activity in the human NELL-1 promoter
luciferase p2213. The p325 truncated NELL-1 construct showed significantly lower
basal level of activity. Nuclear extract from Saos2 cells formed complexes with
site A, B, and C probes and were supershifted with Runx2 antibody. Mutation of
sites A, B, and C significantly decreased basal promoter activity. Furthermore,
mutation of sites B and C had a blunted response to Runx2, whereas mutation of
site A had a lesser effect. Runx2 bound to NELL-1 promoter in vivo. Transfection
of Runx2 in rat osteoblasts upregulated Nell-1 and Ocn expression, and in Runx2
null calvarial cells, both Nell-1 and Ocn expression were rescued. CONCLUSIONS:
Runx2 directly binds to the OSE2 elements and transactivates the human NELL-1
promoter. These results suggest that Nell-1 is likely a downstream target of
Runx2. These findings may also extend our understanding of the molecular
mechanisms governing the pathogenesis of craniosynostosis.
PMID- 17042740
TI - Fission yeast cytoskeletons and cell polarity factors: connecting at the cortex.
AB - Cell polarity is a fundamental property of cells from unicellular to
multicellular organisms. Most of the time, it is essential so that the cells can
achieve their function. The fission yeast Schizosaccharomyces pombe is a powerful
genetic model organism for studying the molecular mechanisms of the cell polarity
process. Indeed, S. pombe cells are rod-shaped and cell growth is restricted at
the poles. The accurate localization of the cell growth machinery at the cell
cortex, which involves the actin cytoskeleton, depends on cell polarity pathways
that are temporally and spatially regulated. The importance of interphase
microtubules and cell polarity factors acting at the cortex of cell ends in this
process has been shown. Here, we review recent advances in knowledge of molecular
pathways leading to the establishment of a cellular axis in fission yeast. We
also describe the role of cortical proteins and mitotic cytoskeletal
rearrangements that control the symmetry of cell division.
PMID- 17042741
TI - Bacterial protein toxins and lipids: role in toxin targeting and activity.
AB - All bacterial toxins, which globally are hydrophilic proteins, interact first
with their target cells by recognizing a surface receptor, which is either a
lipid or a lipid derivative, or another compound but in a lipid environment.
Intracellular active toxins follow various trafficking pathways, the sorting of
which is greatly dependent on the nature of the receptor, notably lipidic
receptor or receptor embedded into a distinct environment such as lipid
microdomains. Numerous other toxins act locally on cell membrane. Indeed,
phospholipase activity is a common mechanism shared by several membrane-damaging
toxins. In addition, many toxins active intracellularly or on cell membrane
modulate host cell phospholipid pathways. Unusually, a few bacterial toxins
require a lipid post-translational modification to be active. Thereby, lipids are
obligate partners of bacterial toxins.
PMID- 17042742
TI - Bacterial protein toxins and lipids: pore formation or toxin entry into cells.
AB - Lipids are hydrophobic molecules which play critical functions in cells, in
particular, they are essential constituents of membranes, whereas bacterial
toxins are mainly hydrophilic proteins. All bacterial toxins interact first with
their target cells by recognizing a surface receptor, which is either a lipid or
a lipid derivative, or another compound but in a lipid environment. Most
bacterial toxins are PFTs (pore-forming toxins) which oligomerize and insert into
the lipid bilayer. A common mechanism of action involves the formation of a beta
barrel structure, resulting from the assembly of individual beta-hairpin(s) from
individual monomers. An essential step for intracellular active toxins is to
translocate their enzymatic part into the cytosol. Some toxins use a
translocation mechanism based on pore formation similar to that of PFTs, others
undergo a yet unclear 'chaperone' process.
PMID- 17042745
TI - Jose Ruiz-Herrera - biographical sketch.
PMID- 17042743
TI - A feedback transcriptional mechanism controls the level of the arginine/lysine
transporter cat-1 during amino acid starvation.
AB - The adaptive response to amino acid limitation in mammalian cells inhibits global
protein synthesis and promotes the expression of proteins that protect cells from
stress. The arginine/lysine transporter, cat-1, is induced during amino acid
starvation by transcriptional and post-transcriptional mechanisms. It is shown in
the present study that the transient induction of cat-1 transcription is
regulated by the stress response pathway that involves phosphorylation of the
translation initiation factor, eIF2 (eukaryotic initiation factor-2). This
phosphorylation induces expression of the bZIP (basic leucine zipper protein)
transcription factors C/EBP (CCAAT/enhancer-binding protein)-beta and ATF
(activating transcription factor) 4, which in turn induces ATF3. Transfection
experiments in control and mutant cells, and chromatin immunoprecipitations
showed that ATF4 activates, whereas ATF3 represses cat-1 transcription, via an
AARE (amino acid response element), TGATGAAAC, in the first exon of the cat-1
gene, which functions both in the endogenous and in a heterologous promoter. ATF4
and C/EBPbeta activated transcription when expressed in transfected cells and
they bound as heterodimers to the AARE in vitro. The induction of transcription
by ATF4 was inhibited by ATF3, which also bound to the AARE as a heterodimer with
C/EBPbeta. These results suggest that the transient increase in cat-1
transcription is due to transcriptional activation caused by ATF4 followed by
transcriptional repression by ATF3 via a feedback mechanism.
PMID- 17042746
TI - Fungal yapsins and cell wall: a unique family of aspartic peptidases for a
distinctive cellular function.
AB - A novel class of aspartic peptidases known as fungal yapsins, whose first member
ScYps1p was identified more than a decade ago in Saccharomyces cerevisiae, is
characteristically modified by the addition of a glycophosphatidylinositol moiety
and has a preference for cleaving substrates C-terminally to mono- and paired
basic residues. Over the years, several other members, first in S. cerevisiae and
then in other fungi, have been identified. The implication of fungal yapsins in
cell-wall assembly and/or remodelling had been suspected for many years. However,
it is only very recently that studies performed on S. cerevisae and Candida
albicans have confirmed their importance for cell-wall integrity. Here, we review
16 years of research, covering all fundamental aspects of these unique enzymes,
in an effort to track their functional significance. We also propose a
nomenclature for fungal yapsins based on their sequence identity with the
founding members of this family, the S. cerevisiae yapsins.
PMID- 17042747
TI - Candida biofilms on implanted biomaterials: a clinically significant problem.
AB - In recent years there has been an increasing appreciation that microbial biofilms
are ubiquitous, which has resulted in a number of studies on infectious diseases
from a biofilm perspective. Biofilms are defined as structured microbial
communities that are attached to a surface and encased in a matrix of
exopolymeric material. A wide range of biomaterials used in clinical practice
have been shown to support colonization and biofilm formation by Candida spp.,
and the increase in Candida infections in the last decades has almost paralleled
the increase and widespread use of a broad range of medical implant devices,
mainly in populations with impaired host defenses. Formation of Candida biofilms
has important clinical repercussions because of their increased resistance to
antifungal therapy and the ability of cells within biofilms to withstand host
immune defenses. Further recognition and understanding of the role of Candida
biofilms in human infection should help in the clinical management of these
recalcitrant infections.
PMID- 17042748
TI - Use of DNA microarray technology and gene expression profiles to investigate the
pathogenesis, cell biology, antifungal susceptibility and diagnosis of Candida
albicans.
AB - The use of DNA microarrays is becoming the method of choice for assaying gene
expression, particularly as costs and complexity are being reduced as the
technology becomes more widespread and better standardized. A DNA array is
nothing but a collection of probes fixed on a solid support. The probes can be
PCR products of ORFs or short intragenic oligonucleotides deposited or
synthesized in situ by photolithographic methods. To date, sequencing projects
for fungal genomes have yielded 10 complete genomes and 21 whole shotgun
sequences, including Candida albicans strain SC5314. Sequencing of the C.
albicans genome has led to the construction of whole-genome DNA microarrays for
in vitro transcription profiling by several universities and companies. The use
of microarray or DNA chip techniques for Candida research has started recently
but the number of studies using this technology is increasing rapidly, in order
to address important remaining questions about pathogenesis, cell biology,
antifungal susceptibility, and diagnosis.
PMID- 17042749
TI - Immunolocalization of chitin synthases in the phytopathogenic dimorphic fungus
Ustilago maydis.
AB - Conserved polypeptides of the chitin synthase genes UmCHS3 and UmCHS6 from the
phytopathogenic fungus Ustilago maydis were utilized as immunogens to obtain
polyclonal antibodies that were purified by affinity procedures. Because of their
similarities at the regions encoded by either polypeptide, it was concluded that
anti-Chs3 antibodies recognized both Chs3 and Chs4 chitin synthases, whereas anti
Chs6 antibodies recognized Chs6 and Chs8 polypeptides. These antibodies were used
to analyze the localization of the corresponding chitin synthases in U. maydis
cells, using both indirect immunofluorescence microscopy and immunoelectron
microscopy with colloidal-gold-labeled secondary antibodies. It was observed that
chitin synthase proteins were accumulated both in the surface and in the
cytoplasm of the fungal cells. Electron microscopy images revealed the
accumulation of clusters of gold particles in vesicles, providing evidence for
the possible origin and destination of chitin synthases in the fungal cells.
PMID- 17042750
TI - An ectophosphatase activity in Cryptococcus neoformans.
AB - There is increasing evidence in the literature showing that fungal pathogens
express biologically active ectoenzymes. The expression of surface phosphatases
at the cell surface of Cryptococcus neoformans, the etiologic agent of
cryptococcosis, was evaluated in the present study. Different isolates of C.
neoformans express ectophosphatase activity, which is not influenced by capsule
size or serotype. The cryptococcal enzyme is an acid phosphatase, inhibited by
classic inhibitors of ectophosphatases, including ammonium molybdate and sodium
salts of fluoride and orthovanadate. Only the inhibition of enzyme activity
caused by sodium orthovanadate has been shown to be irreversible. The
cryptococcal ectoenzyme is also inhibited by Zn2+ and inorganic phosphate, the
final product of reactions catalyzed by phosphatases. The ectophosphatase from C.
neoformans efficiently releases phosphate groups from different phosphorylated
amino acids, giving a higher rate of phosphate removal when phosphothreonine is
used as a substrate. Yeast cells with irreversibly inhibited ectophosphatases are
less capable of adhering to animal epithelial cells than fungi fully expressing
enzyme activity, suggesting that ectoenzyme expression can contribute to the
pathogenesis of C. neoformans.
PMID- 17042751
TI - Cloning and characterization of Sapp2p, the second aspartic proteinase isoenzyme
from Candida parapsilosis.
AB - The human fungal pathogen Candida parapsilosis possesses at least three genes
encoding secreted aspartic proteinases. Whereas the Sapp1p isoenzyme has already
been biochemically characterized, the SAPP2 and SAPP3 gene products have not. The
Sapp2p precursor, pro-Sapp2p, was therefore expressed in Escherichia coli and
purified. Autoactivation of pro-Sapp2p in acidic conditions was inefficient and
resulted in a protein extended by eight amino acids at the N-terminus
(Sapp2p(+8)). The correct promature junction KR/SSPSS was cleaved by trypsin or
by a membrane-bound Kex2-like proteinase from Candida parapsilosis. The mature
Sapp2p obtained by the assisted activation was proteolytically active. Its
activity was more than twofold higher than that of the self-processed protein
species Sapp2p(+8), as measured by the hemoglobin cleavage test. The substrate
specificity of Sapp2p differs from that of Sapp1p. Peptides containing aromatic
residues in the P1 and P1' positions are cleaved poorly by Sapp2p. A fluorogenic
substrate was synthesized to facilitate further studies.
PMID- 17042752
TI - Absence of Gup1p in Saccharomyces cerevisiae results in defective cell wall
composition, assembly, stability and morphology.
AB - Saccharomyces cerevisiae Gup1p and its homologue Gup2p, members of the
superfamily of membrane-bound O-acyl transferases, were previously associated
with glycerol-mediated salt-stress recovery and glycerol symporter activity.
Several other phenotypes suggested Gup1p involvement in processes connected with
cell structure organization and biogenesis. The gup1Delta mutant is also
thermosensitive and exhibits an altered plasma membrane lipid composition. The
present work shows that the thermosensitivity is independent of glycerol
production and retention. Furthermore, the mutant grows poorly on salt, ethanol
and weak carboxylic acids, suggestive of a malfunctioning membrane potential.
Additionally, gup1Delta is sensitive to cell wall-perturbing agents, such as
Calcofluor white, Zymolyase, lyticase and sodium dodecyl sulphate and exhibits a
sedimentation/aggregation phenotype. Quantitative analysis of cell wall
components yielded increased contents of chitin and beta-1,3-glucans and lower
amounts of mannoproteins. Consistently, scanning electron microscopy showed a
strikingly rough surface morphology of the mutant cells. These results suggest
that the gup1Delta is affected in cell wall assembly and stability, although the
Slt2p/MAP kinase from the PKC pathway was phosphorylated during hypo-osmotic
shock to a normal extent. Results emphasize the pleiotropic nature of gup1Delta,
and are consistent with a role of Gulp1p in connection with several pathways for
cell maintenance and construction/remodelling.
PMID- 17042753
TI - Measurements of plasma membrane potential changes in Saccharomyces cerevisiae
cells reveal the importance of the Tok1 channel in membrane potential
maintenance.
AB - K+ is one of the cations (besides protons) whose transport across the plasma
membrane is believed to contribute to the maintenance of membrane potential. To
ensure K+ transport, Saccharomyces cerevisiae cells possess several types of
active and passive transporters mediating the K+ influx and efflux, respectively.
A diS-C3(3) assay was used to compare the contributions of various potassium
transporters to the membrane potential changes of S. cerevisiae cells in the
exponential growth phase. Altogether, the contributions of six K+ transporters to
the maintenance of a stable membrane potential were tested. As confirmed by the
observed hyperpolarization of trk1 trk2 deletion strains, the diS-C3(3) assay is
a suitable method for comparative studies of the membrane potential of yeast
strains differing in the presence/absence of one or more cation transporters. We
have shown that the presence of the Tok1 channel strongly influences membrane
potential: deletion of the TOK1 gene results in significant plasma membrane
depolarization, whereas strains overexpressing the TOK1 gene are hyperpolarized.
We have also proved that plasma membrane potential is not the only parameter
determining the hygromycin B sensitivity of yeast cells, and that the role of
intracellular transporters in protecting against its toxic effects must also be
considered.
PMID- 17042754
TI - Implications of sterol structure for membrane lipid composition, fluidity and
phospholipid asymmetry in Saccharomyces cerevisiae.
AB - Sterols are essential components of the plasma membrane in eukaryotic cells.
Nystatin-resistant erg mutants were used in the present study to investigate the
in vitro effects of altered sterol structure on membrane lipid composition,
fluidity, and asymmetry of phospholipids. Quantitative analyses of the wild type
and mutants erg2, erg3 and erg6 revealed that mutants have lower sterol (free)-to
phospholipid molar ratios than the wild type. Phosphatidylcholine content was
decreased in erg2 and erg3 mutants; however, it was increased in erg6 strains as
compared to normals. Phosphatidylserine content was increased in the erg6 mutant
only. Fluorescence anisotropy decreased with temperature in both probes, and was
lower for mutants than for the wild type, suggesting an increased freedom in
rotational movement due to decreased membrane order. Investigation of changes in
the aminophospholipid transbilayer distribution using two chemical probes,
trinitrobenzene sulfonic acid and fluorescamine, revealed that the amounts of
phosphatidylethanolamine derivatized by these probes were quite similar in both
the wild type and various erg strains. The present findings suggest that adaptive
responses in yeast cells with altered sterol structure are possibly manifested
through changes in membrane lipid composition and fluidity, and not through
transbilayer rearrangement of aminophospholipids.
PMID- 17042755
TI - Production of Man5GlcNAc2-type sugar chain by the methylotrophic yeast Ogataea
minuta.
AB - The methylotrophic yeast Ogataea minuta IFO 10746 was selected as a suitable
strain for producing human-compatible glycoproteins by means of analyses of its
cell-wall mannoproteins. First, the OmURA3 gene encoding an orotidine-5'
phosphate decarboxylase was cloned and disrupted to generate a host strain with a
uracil auxotrophic marker. Second, both the promoters and the terminators from
the OmAOX1 gene encoding an alcohol oxidase for an inducible promoter, or those
from the OmTDH1 gene encoding a glyceraldehyde-3-phosphate dehydrogenase for a
constitutive promoter, were isolated to construct an expression vector system for
heterologous genes. Next, the OmOCH1 gene encoding a starting enzyme with alpha
1,6-mannosyltransferase activity to form a backbone of the N-linked outer sugar
chain peculiar to yeast was disrupted, and an alpha-1,2-mannosidase gene from
Aspergillus saitoi with an endoplasmic reticulum retention signal (HDEL) under
the control of the OmAOX1 promoter was introduced to convert the sugar chain to
Man5GlcNAc2 in O. minuta. As a result, we succeeded in breeding a new
methylotrophic yeast, O. minuta, producing a Man5GlcNAc2-high-mannose-type sugar
chain as a prototype of a human-compatible sugar chain. We also elucidate here
the usefulness of the strategy for producing human-compatible sugar chains in
yeast.
PMID- 17042756
TI - Effect of farnesol on Candida dubliniensis biofilm formation and fluconazole
resistance.
AB - Candida dubliniensis and Candida albicans are dimorphic fungal species with a
number of pathogenic capabilities, including biofilm formation, systemic
infection and development of fluconazole resistance. In this study, the ability
of farnesol to disrupt these virulence capabilities was investigated. Biofilm
assessment and susceptibility studies indicated antifungal and antibiofilm
properties for farnesol on both species with a disruptive effect on the cell
membrane. Synergy testing of farnesol and fluconazole in resistant strains
resulted in reversal of fluconazole resistance, indicating a potential
application for farnesol as an adjuvant therapeutic agent.
PMID- 17042757
TI - Biofilm formation by Candida albicans mutants for genes coding fungal proteins
exhibiting the eight-cysteine-containing CFEM domain.
AB - Several features and functions of a Candida albicans gene, PGA10 (also designated
as RBT51), coding for a putative polypeptide species belonging to a subset of
fungal proteins containing an eight-cysteine domain referred as CFEM (Common in
several Fungal Extracellular Membrane proteins), are described. The ORF of the
gene (ORF19.5674) encoded a protein of 250 amino acids, with a predicted
molecular mass of 25.17 kDa. The product of the PGA10 gene also exhibited some
features reminiscent of a class II-type hydrophobin. Deletion of PGA10 resulted
in a cascade of pleiotropic effects, mostly affecting cell-surface-related
properties. Thus, the null pga10Delta mutant displayed an increased sensitivity
to cell-wall-perturbing agents and formed fragile biofilms that appeared
partially split and weakly attached to the substratum. The biofilm-forming
ability of several C. albicans mutants with single, double and triple deletions
of genes encoding other protein species also containing the CFEM domain (RBT5 and
WAP1/CSA1) was determined. These mutants also exhibited an abnormal ability to
form biofilms. Overall, the evidence presented here suggests that fungal proteins
containing the CFEM domain (Pga10p/Rbt51p, Rbt5p and Wap1p/Csa1p) may play a key
role in the formation, development and/or maintenance of the biofilm structure in
C. albicans.
PMID- 17042758
TI - An in vitro assay to study the transcriptional response during adherence of
Candida albicans to different human epithelia.
AB - Adhesion to mammalian epithelia is one of the prerequisites that are essential to
accomplish pathogenesis of Candida albicans in the mammalian host. In this
context C. albicans is able to adhere to a plethora of different cell types
providing different microenvironments for colonization. To study the response of
C. albicans adhering to different surfaces on the transcriptional level we have
established an in vitro adhesion assay exploiting confluent monolayers of the
human colorectal carcinoma cell line Caco-2 or epidermoid vulvo-vaginal A-431
cells. Candida albicans very efficiently adheres to these epithelia growing as
hyphae. Using whole-genome DNA microarrays comprising probes for almost 7000
predicted ORFs we found that transcriptional profiles of C. albicans adhering to
Caco-2 or to A-431 cells, although very similar, still significantly differ from
those of Candida cells adhering to plastic surfaces. Differences became even more
obvious when comparing C. albicans cells either growing in an adherent manner or
in suspension culture. Correspondingly, we found for several cell surface genes,
including PRA1, PGA23, PGA7 and HWP1, an adhesion-dependent induction of
transcription. Obviously, C. albicans is able to respond specifically to very
subtle differences in the environment during adhesion to various growth
substrates.
PMID- 17042759
TI - Rapid PCR-based test for identifying Candida albicans by using primers derived
from the pH-regulated KER1 gene.
AB - A PCR-based method in combination with a simple, reliable and inexpensive DNA
extraction procedure for rapid detection of Candida albicans clinical isolates is
described here. The extraction protocol is based on a combination of chemical
(NaOH and detergents) and physical (boiling) treatments, thus avoiding many of
the problems inherent in the currently available DNA extraction protocols
(basically the use of expensive and/or toxic chemical reagents), and may be
useful for daily clinical routine. The PCR-based system described here uses a
single pair of primers (SC1F and SC1R) deduced from the C. albicans-specific KER1
gene sequence. These primers amplify a 670-bp fragment of the KER1 gene. All the
clinical C. albicans isolates generated the expected 670-bp amplicon. Other non
albicans Candida species, including the azole-resistant C. krusei and C.
glabrata, and the very closely related C. dubliniensis, failed to amplify any DNA
fragment. The PCR results reported here suggest that amplification with SC1F and
SC1R primers is species specific and, consequently, may be useful for
specifically identifying C. albicans strains.
PMID- 17042760
TI - Four-year evaluation of myocardial and liver iron assessed prospectively with
serial MRI scans in young patients with beta-thalassaemia major: comparison
between different chelation regimens.
AB - This study was conducted in order to assess myocardial and liver iron
concentrations (LICs) using serial magnetic resonance imaging (MRI) scans in
patients with beta-thalassaemia major, over a 4-yr period, and consequently to
compare the effectiveness of different chelation regimens. Fifty children and
young adults with beta-thalassaemia major (27 boys and 23 girls) were recruited
(mean age: 14.74 +/- 3.67 yr). All patients underwent detailed clinical
examination, electrocardiography, echocardiography, myocardial and liver MRI at
the beginning of the study, 2 and 4 yr after. Additionally, serum ferritin levels
were regularly measured and data regarding LICs assessed by percutaneous liver
biopsy were available in 26 patients. Both myocardial and liver MRI values showed
a moderate inverse correlation with age (r = -0.379, P < 0.001 and r = -0.376, P
< 0.001, respectively). Liver MRI was better correlated with serum ferritin
concentrations (r = -0.342, P < 0.001) than myocardial MRI (r = -0.186, P =
0.011). Liver MRI values were highly correlated with LICs derived from
percutaneous liver biopsy (r = -0.863, P < 0.001), whereas myocardial MRI values
did not correlate at all with measurements derived from echocardiography.
Regarding iron chelation treatment, patients receiving combined therapy with
deferiprone and deferoxamine (DFO) significantly reduced myocardial iron overload
during the 4-yr study period, whilst patients in monotherapy with DFO showed a
significant increase in LIC.
PMID- 17042761
TI - Detection of early abnormalities in gastric function in first-degree relatives of
patients with pernicious anemia.
AB - BACKGROUND: Pernicious anemia (PA), as many other autoimmune disorders, has a
trend to appear in other members of the family of the affected patients. Although
this fact has been recognized since some decades ago, less is known about the
frequency with which the abnormalities detected in the patients appear also in
their relatives, the correlations that exist among these abnormalities and to
what extent these markers of the disease relate to serum cobalamin concentration.
SUBJECTS AND RESULTS: For these reasons we studied the values of some markers of
PA in a group of 79 first-degree relatives and we detected that the most frequent
abnormalities are a decrease in serum pepsinogen I (22.7% of cases), an increase
in serum gastrin (16.5% of cases) and in parietal cell antibody at a titer >or=40
(23.4% of cases). From a functional point of view, a decrease in hydrogen
excretion in a magnesium breath test, indicative of achlorhydria, is also
frequent (29.1%). The fall in cobalamin concentration runs in parallel with these
abnormalities. The concentration of this vitamin was below normal levels in as
much as 15.2% of cases. CONCLUSION: These findings emphasize the need for
searching for the presence of occult or latent PA in relatives of patients with
this diagnosis, not only to prevent the development of anemia but also to avoid
other undesirable consequences of cobalamin deficiency.
PMID- 17042762
TI - Effect of CD34 cell dose on hematopoietic reconstitution and outcome in 508
patients with multiple myeloma undergoing autologous peripheral blood stem cell
transplantation.
AB - BACKGROUND: We analyzed the hematopoietic reconstitution and outcome of 508
patients with multiple myeloma (MM) with respect to the number of CD34+ cells
reinfused at our center. PATIENTS AND METHODS: Each cohort of 390 patients
(unselected CD34+ cell transplant) and 118 patients (CD34+ selected transplant)
was divided into four subgroups. Among the 390 transplantations, 86 patients
received a high dose (HD-) of > or =6.50 x 10(6) unselected CD34+ cells/kg, 116
patients a low dose (LD-) of <3.00 x 10(6) CD34+ cells/kg. Among the patients
treated with CD34+ selected PBSC, 34 received > or =6.50 x 10(6) CD34+ cells/kg
(HD+) and 16 <3.00 x 10(6) CD34+ cells/kg (LD+). RESULTS: HD- patients
experienced a reduced median time to leukocyte (13 d vs. 14 d) (P < 0.001) and
platelet reconstitution >20 x 10(9)/L (10 d vs. 12 d) (P < 0.001). Similarly, HD+
showed a reduced median time to leukocyte (12 d vs. 15 d) (P < 0.001) and
platelet recovery >20 x 10(9)/L (10 d vs. 11 d) (P = 0.058). CD34+ cell-dose was
significant for long-term platelet recovery at day 360 (unselected transplant P =
0.015, selected transplant P = 0.023). Number of transplanted CD34+ cells had no
significant impact on transplant related mortality, overall survival or CR/PR
rates within 100 d. In terms of supportive care the differences of high-/low-dose
grafts were minimal. CONCLUSIONS: These results confirm that high doses of CD34+
PBSC shorten hematopoietic reconstitution and reduce hospitalization.
Nevertheless secure engraftment results from transplantation of 2.00-3.00 x 10(6)
CD34+ cells/kg. As 60% of our pretreated patients are able to collect > or =5.00
x 10(6) CD34+ cells/kg within a single leukapheresis, division into two or more
freezing bags allows safe tandem transplantation in the majority of MM patients.
PMID- 17042764
TI - Appraisal of current vitamin K dosing algorithms for the reversal of over
anticoagulation with warfarin: the need for a more tailored dosing regimen.
AB - Warfarin is the most commonly prescribed oral anticoagulant in the UK for the
treatment and prevention of thromboembolic disorders. Vitamin K administration is
an effective way of reversing excessive anticoagulation. Over-anticoagulated
patients present with a wide range of international normalized ratio (INR) values
and may respond differently to a fixed dose of vitamin K. Current dosing
algorithms for vitamin K administration in the non-urgent treatment of over
anticoagulation do not take this variability in response into account.
Consequently, over a third of over-anticoagulated patients still remain outside
their target INR 24 h after treatment. Such patients are therefore prone to
either haemorrhage (if the patient is still over-anticoagulated) or
thromboembolism (if the INR reversal is over-corrected). A number of factors such
as patient age, body weight, co-morbidity, frailty, warfarin daily dose and
CYP2C9 and VKORC1 polymorphism could affect response to vitamin K and thus the
rate and extent of INR reversal. There is a need for a more individualized
approach to the reversal of over-anticoagulation in asymptomatic or mildly
haemorrhagic patients in order to improve the safety of warfarin therapy.
PMID- 17042765
TI - Platelet autoantibodies are common in hepatitis C infection, irrespective of the
presence of thrombocytopenia.
AB - OBJECTIVE: To investigate the generation of platelet antibodies in hepatitis C
virus (HCV)-infected individuals and their relation to the development to
thrombocytopenia with the aim of using their detection as a diagnostic aid of
immune thrombocytopenia in these patients. MATERIALS AND METHODS: We tested by
the monoclonal antibody-specific immobilization of platelet antigen assay (MAIPA)
for the presence of platelet antibodies against specific glycoprotein (GP)
targets (GPIIb/IIIa, GPIb/IX, GPIa/IIa, GPIIIb, GPV, and FcRgammaIIa) in 48 HCV
infected individuals of various stages of disease and compared the results with
those from 35 patients with alcoholic liver cirrhosis. RESULTS: Thirty-two HCV
infected individuals (66%) had detectable platelet antibodies. The most common
target was GPIIb/IIIa, but all other GP were also targets. Results were not
different from patients with alcoholic liver cirrhosis. There was no correlation
between antibodies and platelet counts, or the stage of disease, or the viral
genotype, or a discernible influence of treatment with alpha-interferon.
CONCLUSION: While platelet autoantibodies are common in individuals with HCV
infection, their detection does not assist in the diagnosis of immune
thrombocytopenia.
PMID- 17042766
TI - Thrombotic thrombocytopenic purpura associated with renal failure after
autologous transplantation for multiple myeloma successfully treated with
rituximab.
AB - Thrombotic thrombocytopenic purpura (TTP) is a haematological syndrome
characterised by a dramatic onset requiring an urgent treatment with plasma
exchange (PE). However, the prognosis is still dismal for PE related
complications, a rate of failure and remarkable frequencies of relapse. TTP post
transplantation is largely described as an outstanding, unusual complication of
allogenic transplantation, but it is rarely mentioned after autologous
transplantation. We describe a 62-year-old Caucasian patient who presented with
TTP, accompanied by renal failure, after an autologous transplantation for
multiple myeloma. PE together with hemodialysis was rapidly initiated but without
any benefit. Since empirical administration of Rituximab, anti CD20 monoclonal
antibody,was reported to be effective, we administered four courses of Rituximab
inducing a complete remission of TTP and subsequently of the renal failure. This
response to Rituximab in TTP post transplantation is suggestive of a possible
implication of B-lymphocytes in the pathogenesis of TTP and it paves the way for
an investigational approach in this settings.
PMID- 17042767
TI - A novel Indian beta-thalassemia mutation in the CACCC box of the promoter region.
AB - This is the first report of a previously undescribed mutation in Indian subjects
of the CACCC box of promoter region for beta-globin, which in combination with a
common mutation produces thalassemia major in the offspring of the family.
PMID- 17042768
TI - Intrathecal donor lymphocyte infusion for the treatment of suspected refractory
lymphomatous meningitis: a case report.
AB - A 43-year-old female with large T-cell non-Hodgkin's lymphoma and central nervous
system (CNS) involvement underwent HLA-identical-sibling peripheral blood stem
cell transplantation (SCT) during her third complete remission. She presented a
possible refractory CNS relapse 5 months after the transplant. She was then
treated with intrathecal (IT) donor lymphocyte infusions (DLI). No side effects
were observed after three DLI injections. The patient died 13 months later from
infectious complications with no evidence of progressive disease. To our
knowledge, this is the first case report of IT DLI for possible refractory
lymphomatous meningitis.
PMID- 17042769
TI - Individually determined dosing of filgrastim after autologous peripheral stem
cell transplantation in patients with malignant lymphoma--results of a
prospective multicentre controlled trial.
AB - OBJECTIVES: To explore the safety and effectiveness of the individually
determined application granulocyte-colony stimulating factor (G-CSF) after
autologous peripheral blood stem cell transplantation (ASCT). METHODS: The
administration of G-CSF from day +5 (arm A) was compared in a randomised,
controlled trial with delayed, individually determined administration (G-CSF
started when WBC >or= 0.5 x 10(9)/L and ANC >or= 0.1 x 10(9)/L or at day +10; arm
B), and with placebo (arm C). RESULTS: One hundred and six patients, median age
45 (range 21-64), all with malignant lymphoma treated with BEAM chemotherapy were
analysed. A significant difference in the time to neutrophil engraftment and in
the duration of neutropenia <0.5 x 10(9)/L and <1.0 x 10(9)/L was observed
between the arms (P = 0.04-<0.0001) with a 1-d prolongation of the median
durations in arm B in comparison with arm A but a 2-4-d prolongation in the
placebo arm C in comparison with arm B. The median number and range of days to
neutrophil engraftment >0.5 x 10(9)/L after graft re-infusion was 10 (9-14) in
arm A; 11 (9-19) in arm B; and 14 (10-30) in arm C (P < 0.0001). Engraftment of
platelets to >20 x 10(9)/L and >50 x 10(9)/L was significantly delayed in the
arms using G-CSF in comparison with placebo (P = 0.04-0.002) without any increase
in bleeding or in transfusion requirement. There was no difference in the
incidence and duration of transplant-related complications and their treatment
between the arms. CONCLUSIONS: Our study has confirmed the safety of individually
determined administration of G-CSF. The optimal timing of G-CSF application after
ASCT in patients with good-quality grafts is shortly before expected spontaneous
engraftment.
PMID- 17042770
TI - An antecedent diagnosis of refractory anemia with excess blasts has no influence
on mobilization of peripheral blood stem cells and hematopoietic recovery after
autologous stem cell transplantation in acute myeloid leukemia.
AB - Several studies have reported data on factors influencing mobilization of
peripheral blood stem cells (PBSC) in non-myeloid malignancies. On the contrary,
data from patients with acute myeloid leukemia (AML) are very limited, in
particular, as the impact of an antecedent diagnosis of refractory anemia with
excess blasts (RAEB) on mobilization of PBSCs as well as hematopoietic recovery
after autologous stem cell transplantation (ASCT) is concerned. We
retrospectively analyzed a cohort of 150 consecutive AML patients in first
complete remission in order to make a comparison between patients with de novo
AML and secondary AML (s-AML) in terms of CD34 positive (CD34+) cells
mobilization and number of leukapheresis needed to collect at least one single
stem cell graft. Data concerning hematopoietic recovery after ASCT were also
compared. The successful mobilization rate (>2 x 10(6) CD34+ cells/kg) was
comparable between de novo AML patients (87%) and those with s-AML (76%), P:0.21.
No statistically significant difference was found in terms of either median
number of CD34+ cells collected (P:0.44) or CD34+ cells peak in peripheral blood
(P:0.28). Both groups of patients needed a median of two apheresis (P:0.45) and
no difference was found on the median number of CD34+ cells collected per single
apheresis (P:0.59). Finally, neutrophil and platelet recovery after ASCT were
comparable between the two groups. An antecedent diagnosis of RAEB has no impact
on mobilization and collection of PBSCs in AML as well as on hematopoietic
recovery after ASCT.
PMID- 17042771
TI - Potentiation of erythroid abnormalities following macrophage depletion in aged
rats.
AB - OBJECTIVES: The effects of prolonged macrophage depletion on haematological
parameters were investigated in aged rats and compared with those in young ones.
METHODS: Four weekly i.v. injections of dichloromethylene diphosphonate
containing liposomes (Cl2MDP-CL) were employed to achieve a prolonged depletion
of bone marrow (BM) and spleen macrophages. The number of BM macrophages was then
assessed by flow cytometry, whereas the spleen clearance function was judged by
the elimination of oxidised red blood cells (RBC). Haematological parameters and
signs of RBC ageing (reduced MCV, increased density and augmented 4.1a/4.1b
membrane protein ratio) were determined. Finally, the recovery from phlebotomy
induced acute anaemia was investigated. RESULTS: Following the Cl2MDP-CL
treatment, in comparison with young rats, the aged animals showed: (i) reduced
numbers of BM macrophages; (ii) greater impairment of spleen clearance function;
(iii) similar anaemic condition and signs of RBC ageing; (iv) greater increase in
white blood cell (WBC) numbers (mainly neutrophils). In addition, whereas aged
control rats showed a recovery from phlebotomy-induced acute anaemia which was
similar to that of the untreated young animals, in the aged-treated rats, a
significantly diminished/delayed restoration of RBC, Hb and reticulocyte to
normal values was observed, accompanied by a significantly higher increase in WBC
numbers than in the other groups of animals. CONCLUSION: Haematological
abnormalities because of Cl2MDP-CL-induced macrophage depletion are potentiated
in aged rats in which the BM regenerative potential of the erythroid lineage as
well as the clearance function of the spleen appear compromised. Thus, in aged
rats, macrophage dysfunction is likely to interfere with erythroid homeostasis
particularly during haemopoietic stress.
PMID- 17042772
TI - H63D homozygotes with hyperferritinaemia: Is this genotype, the primary cause of
iron overload?
AB - OBJECTIVES: Hereditary haemochromatosis is a disease that affects iron metabolism
and leads to iron overload. Homozygosity for the H63D mutation is associated with
increased transferrin saturation (TS) and ferritin levels. Our objective was to
find out if the homozygosity of H63D mutation was the primary cause of iron
overload. PATIENTS AND METHODS: We studied 45 H63D homozygotes (31 males and 14
females) with biochemical iron overload and/or clinical features of
haemochromatosis. The simultaneous detection of 18 known HFE, TFR2 and FPN1
mutations and sequencing of the HAMP gene were performed to rule out the possible
existence of genetic modifier factors related with iron overload. RESULTS: Values
of biochemical iron overload, measured as percentage TS and serum ferritin
concentration (SF), in our H63D homozygotes were significantly higher in patients
than in controls: TS 55 +/- 15% vs. 35 +/- 15% and SF 764 (645-883) microg/L vs.
115 (108-123) microg/L for patients and controls, respectively. These H63D
homozygotes presented extreme hyperferritinaemia and no additional mutations in
HFE, TFR2, FPN1 and HAMP genes were detected. CONCLUSIONS: The lack of additional
mutations in our H63D homozygotes suggests that this genotype could be the
primary cause of iron overload in these patients. Despite our results, we cannot
entirely discount the possibility that one or more genetic modifier factor
exists, simply because we were unable to find it, although there was a precedent
in the HFE gene. Genetic modifier factors have been described for C282Y mutations
in the HFE gene, but at the present time they have never been reported in H63D
homozygotes.
PMID- 17042773
TI - Low tolerance and high toxicity of thalidomide as maintenance therapy after
double autologous stem cell transplant in multiple myeloma patients.
AB - Although a double autologous peripheral blood stem cell transplant (APBSCT) is an
effective therapy for patients (pts) with multiple myeloma and extends
progression-free survival and overall survival, pts show a continued pattern of
recurrent disease. The feasibility and tolerability of thalidomide (Thal)
administered in the post-transplantation period as maintenance therapy was tested
in 17 pts at a dose of 100 mg/d starting between 3 and 5 months after the second
transplantation and continuing either until toxicity precluded further therapy or
until pts had disease progression. After a median administration of 13 months
(range: 3-26), 76.5% (13 pts) failed to tolerate Thal because of: transiet
ischemic attack (three pts), severe fatigue (two), neutropenia (one),
piastrinopenia (one), severe opportunistic infectious (two), erectile impotence
(one), gastrointestinal toxicity (anorexia with weight loss one), peripheral
neuropathy (two). After a median follow-up of 36 months (range: 10-59) from the
second transplant, 13 patients attained a CR + near CR (with a conversion rate
from 47.1% to 76.5%). In conclusion, Thal as maintenance therapy after double
ASCT is associated with low feasibility and high toxicity and could prevent a
lengthy use of this antineoplastic agent.
PMID- 17042774
TI - Peripheral blood haematopoietic progenitor cells in patients with beta
thalassaemia major receiving desferrioxamine or deferiprone as chelation therapy.
AB - OBJECTIVES: The main adverse effect of deferiprone is the development of
neutropenia, which occurs via an unknown mechanism. We aimed to gain insight into
the pathogenesis of deferiprone-induced neutropenia by assessing the peripheral
blood haematopoietic progenitor cells. METHODS: Sixteen patients with beta
thalassaemia were studied; nine (Group A) were receiving desferrioxamine and
seven (Group B) deferiprone. Ten healthy individuals comprised the control group
(Group C). RESULTS: Granulocyte-erythrocyte-monocyte-megakaryocyte colony forming
units were significantly more in Groups A and B compared with Group C.
Granulocyte-macrophage colony forming units (CFU-GM) were significantly more in
Group B compared with Group C. Macrophage colony forming units were significantly
less in Group B compared with Group C. Granulocyte colony forming units (CFU-G)
were significantly more in Group A compared with Group C. We found a trend in the
difference in the number of CFU-G between patients' groups (P = 0.123). Adding
serum from patients receiving deferiprone to cultures of controls resulted in a
maturation arrest of the granulocytic lineage. CONCLUSION: Our findings point to
a maturation arrest at the level of CFU-GM as a potential mechanism of
deferiprone-induced neutropenia.
PMID- 17042775
TI - Hepcidin--central regulator of iron metabolism.
AB - The knowledge about mammalian iron metabolism has advanced dramatically over the
past decades. Studies of genetics, biochemistry and molecular biology allowed us
the identification and characterization of many of the molecules involved in
regulation of iron homeostasis. Important progresses were made after the
discovery in 2000 of a small peptide--hepcidin--that has been proved to play a
central role in orchestration on iron metabolism also providing a link between
iron metabolism and inflammation and innate immunity. Hepcidin directly interacts
with ferroportin (FPN), the only known mammalian iron exporter, which is
expressed by enterocytes, macrophages and hepatocytes. The direct hepcidin-FPN
interaction allows an adaptative response from the body in situations that alter
normal iron homeostasis (hypoxia, anemia, iron deficiency, iron overload, and
inflammation).
PMID- 17042776
TI - Meta-analysis: Alvimopan vs. placebo in the treatment of post-operative ileus.
AB - BACKGROUND: Alvimopan is a selective, competitive mu-opioid receptor antagonist
with limited oral bioavailability which may be used to reduce length of post
operative ileus. AIM: The study compared alvimopan with placebo following bowel
resection or total abdominal hysterectomy. METHODS: A meta-analysis of randomized
controlled trials published between 2001 and 2006 of alvimopan vs. placebo was
performed. The primary efficacy end-points were composite measures of passage of
flatus, stool, and tolerance of solid food (GI-3) and passage of stool and
tolerance of solid food (GI-2). The incidence of treatment emergent adverse
events was assessed. RESULTS: Five trials matched the selection criteria,
reporting on 2195 patients. A total of 1521 (69.3%) had alvimopan and 674 (30.7%)
placebo. GI-3 significantly improved (hazard ratio 1.30; 95% confidence intervals
1.16, 1.45, P < 0.001), as did GI-2 (hazard ratio 1.61; 95% confidence intervals
1.26, 2.05, P < 0.001) on alvimopan 12 mg. Time to discharge (hazard ratio 1.26;
95% confidence intervals 1.13, 1.40, P < 0.001), time to bowel motion (hazard
ratio 1.74; 95% confidence intervals 1.29, 2.35, P < 0.001), and time to solid
food (hazard ratio 1.14; 95% confidence intervals 1.01, 1.30, P < 0.04) also
improved significantly. No difference was noted in the incidence of treatment
emergent adverse events. CONCLUSIONS: Alvimopan showed significant advantages
over placebo in restoring gastro-intestinal function, and reduced time to
discharge following major abdominal surgery, with acceptable side effects.
PMID- 17042777
TI - Chronic unremitting urticaria: is the use of antihistamines above the licensed
dose effective? A preliminary study of cetirizine at licensed and above-licensed
doses.
AB - Recently, several authors have suggested an off-label increase of antihistamine
dosage should be given to patients with chronic urticaria (CU) not responding to
the usual, recommended doses, in order to gain better control of the disease.
However, this recommendation is not evidence-based. The objective of this study
was to assess the effectiveness of increased doses of antihistamines in patients
with CU showing poor control at recommended doses. In total, 22 adult patients
with moderate/severe CU not controlled with the usual antihistamine doses were
studied. These subjects recorded urticaria severity on a visual analogue scale
(range 0-10) for 2 weeks. During the first week, they were treated with
cetirizine at the licensed dose (10 mg/day), and with a three-fold increased dose
(10 mg x 3/day) during week 2. Only 1 patient (5%) responded satisfactorily to
the increased dosage of antihistamine; in the remaining 21 subjects, urticaria
scores did not change, and these patients had to be treated with steroids,
ciclosporin, and in 1 case with cyclophosphamide. Disease control was eventually
gained in all cases. This study suggests that the proportion of patients with
severe CU that may gain a better control of their disease with high, off-label
doses of antihistamines is probably small, and that most patients will eventually
have to undergo more aggressive treatments.
PMID- 17042778
TI - Functional characterization and Me ion specificity of a Ca-citrate transporter
from Enterococcus faecalis.
AB - Secondary transporters of the bacterial CitMHS family transport citrate in
complex with a metal ion. Different members of the family are specific for the
metal ion in the complex and have been shown to transport Mg(2+)-citrate, Ca(2+)
citrate or Fe(3+)-citrate. The Fe(3+)-citrate transporter of Streptococcus mutans
clusters on the phylogenetic tree on a separate branch with a group of
transporters found in the phylum Firmicutes which are believed to be involved in
anaerobic citrate degradation. We have cloned and characterized the transporter
from Enterococcus faecalis EfCitH in this cluster. The gene was functionally
expressed in Escherichia coli and studied using right-side-out membrane vesicles.
The transporter catalyzes proton-motive-force-driven uptake of the Ca(2+)-citrate
complex with an affinity constant of 3.5 microm. Homologous exchange is catalyzed
with a higher efficiency than efflux down a concentration gradient. Analysis of
the metal ion specificity of EfCitH activity in right-side-out membrane vesicles
revealed a specificity that was highly similar to that of the Bacillus subtilis
Ca(2+)-citrate transporter in the same family. In spite of the high sequence
identity with the S. mutans Fe(3+)-citrate transporter, no transport activity
with Fe(3+) (or Fe(2+)) could be detected. The transporter of E. faecalis
catalyzes translocation of citrate in complex with Ca(2+), Sr(2+), Mn(2+), Cd(2+)
and Pb(2+) and not with Mg(2+), Zn(2+), Ni(2+) and Co(2+). The specificity
appears to correlate with the size of the metal ion in the complex.
PMID- 17042779
TI - Saccharomyces cerevisiae alpha1,6-mannosyltransferase has a catalytic potential
to transfer a second mannose molecule.
AB - In yeast, the N-linked oligosaccharide modification in the Golgi apparatus is
initiated by alpha1,6-mannosyltransferase (encoded by the OCH1 gene) with the
addition of mannose to the Man(8)GlcNAc(2) or Man(9)GlcNAc(2) endoplasmic
reticulum intermediates. In order to characterize its enzymatic properties, the
soluble form of the recombinant Och1p was expressed in the methylotrophic yeast
Pichia pastoris as a secreted protein, after truncation of its transmembrane
region and fusion with myc and histidine tags at the C-terminus, and purified
using a metal chelating column. The enzymatic reaction was performed using
various kinds of pyridylaminated (PA) sugar chains as acceptor, and the products
were separated by high performance liquid chromatography. The recombinant Och1p
efficiently transferred a mannose to Man(8)GlcNAc(2)-PA and Man(9)GlcNAc(2)-PA
acceptors, while Man(5)GlcNAc(2)-PA, which completely lacks alpha1,2-linked
mannose residues, was not used as an acceptor. At high enzyme concentrations, a
novel product was detected by HPLC. Analysis of the product revealed that a
second mannose was attached at the 6-O-position of alpha1,3-linked mannose
branching from the alpha1,6-linked mannose that is attached to beta1,4-linked
mannose of Man(10)GlcNAc(2)-PA produced by the original activity of Och1p. Our
results indicate that Och1p has the potential to transfer two mannoses from GDP
mannose, and strictly recognizes the overall structure of high mannose type
oligosaccharide.
PMID- 17042780
TI - Diversity of human U2AF splicing factors.
AB - U2 snRNP auxiliary factor (U2AF) is an essential heterodimeric splicing factor
composed of two subunits, U2AF(65) and U2AF(35). During the past few years, a
number of proteins related to both U2AF(65) and U2AF(35) have been discovered.
Here, we review the conserved structural features that characterize the U2AF
protein families and their evolutionary emergence. We perform a comprehensive
database search designed to identify U2AF protein isoforms produced by
alternative splicing, and we discuss the potential implications of U2AF protein
diversity for splicing regulation.
PMID- 17042781
TI - Characterization of novel M-superfamily conotoxins with new disulfide linkage.
AB - The M-superfamily with the typical Cys framework (-CC-C-C-CC-) is one of the
seven major superfamilies of conotoxins found in the venom of cone snails. Based
on the number of residues in the last Cys loop (between C4 and C5), M-superfamily
conotoxins can be provisionally categorized into four branches (M-1, M-2, M-3, M
4) [Corpuz GP, Jacobsen RB, Jimenez EC, Watkins M, Walker C, Colledge C, Garrett
JE, McDougal O, Li W, Gray WR, et al. (2005) Biochemistry44, 8176-8186]. Here we
report the purification of seven M-superfamily conotoxins from Conus marmoreus
(five are novel and two are known as mr3a and mr3b) and one known M-1 toxin tx3a
from Conus textile. In addition, six novel cDNA sequences of M-superfamily
conotoxins have been identified from C. marmoreus, Conus leopardus and Conus
quercinus. Most of the above novel conotoxins belong to M-1 and M-2 and only one
to M-3. The disulfide analyses of two M-1 conotoxins, mr3e and tx3a, revealed
that they possess a new disulfide bond arrangement (C1-C5, C2-C4, C3-C6) which is
different from those of the M-4 branch (C1-C4, C2-C5, C3-C6) and M-2 branch (C1
C6, C2-C4, C3-C5). This newly characterized disulfide connectivity was confirmed
by comparing the HPLC profiles of native mr3e and its two regioselectively folded
isoforms. This is the first report of three different patterns of disulfide
connectivity in conotoxins with the same cysteine framework.
PMID- 17042782
TI - Binding areas of urokinase-type plasminogen activator-plasminogen activator
inhibitor-1 complex for endocytosis receptors of the low-density lipoprotein
receptor family, determined by site-directed mutagenesis.
AB - Some endocytosis receptors related to the low-density lipoprotein receptor,
including low-density lipoprotein receptor-related protein-1A, very-low-density
lipoprotein receptor, and sorting protein-related receptor, bind protease
inhibitor complexes, including urokinase-type plasminogen activator (uPA),
plasminogen activator inhibitor-1 (PAI-1), and the uPA-PAI-1 complex. The unique
capacity of these receptors for high-affinity binding of many structurally
unrelated ligands renders mapping of receptor-binding surfaces of serpin and
serine protease ligands a special challenge. We have mapped the receptor-binding
area of the uPA-PAI-1 complex by site-directed mutagenesis. Substitution of a
cluster of basic residues near the 37-loop and 60-loop of uPA reduced the
receptor-binding affinity of the uPA-PAI-1 complex approximately twofold.
Deletion of the N-terminal growth factor domain of uPA reduced the affinity 2-4
fold, depending on the receptor, and deletion of both the growth factor domain
and the kringle reduced the affinity sevenfold. The binding affinity of the uPA
PAI-1 complex to the receptors was greatly reduced by substitution of basic and
hydrophobic residues in alpha-helix D and alpha-helix E of PAI-1. The
localization of the implicated residues in the 3D structures of uPA and PAI-1
shows that they form a continuous receptor-binding area spanning the serpin as
well as the A-chain and the serine protease domain of uPA. Our results suggest
that the 10-100-fold higher affinity of the uPA-PAI-1 complex compared with the
free components depends on the bonus effect of bringing the binding areas on uPA
and PAI-1 together on the same binding entity.
PMID- 17042783
TI - Odorant binding protein has the biochemical properties of a scavenger for 4
hydroxy-2-nonenal in mammalian nasal mucosa.
AB - Odorant binding proteins (OBP) are soluble lipocalins produced in large amounts
in the nasal mucosa of several mammalian species. Although OBPs can bind a large
variety of odorous compounds, direct and exclusive involvement of these proteins
in olfactory perception has not been clearly demonstrated. This study
investigated the binding properties and chemical resistance of OBP to the
chemically reactive lipid peroxidation end-product 4-hydroxy-2-nonenal (HNE), in
an attempt to establish a functional relationship between this protein and the
molecular mechanisms combating free radical cellular damage. Experiments were
carried out on recombinant porcine and bovine OBPs and results showed that both
forms were able to bind HNE with affinities comparable with those of typical OBP
ligands (K(d) = 4.9 and 9.0 microm for porcine and bovine OBP, respectively).
Furthermore, OBP functionality, as determined by measuring the binding of the
fluorescent ligand 1-aminoanthracene, was partially lost only when incubating HNE
levels and exposure time to HNE exceeded physiological values in nasal mucosa.
Finally, preliminary experiments in a simplified model resembling nasal
epithelium showed that extracellular OBP can preserve the viability of an
epithelial cell line derived from bovine turbinates exposed to toxic amounts of
the aldehyde. These results suggest that OBP, which is expressed at millimolar
levels, might reduce HNE toxicity by removing from the nasal mucus a significant
fraction of the aldehyde that is produced as a consequence of direct exposure to
the oxygen present in inhaled air.
PMID- 17042784
TI - The MprF protein is required for lysinylation of phospholipids in listerial
membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on
Listeria monocytogenes.
AB - Pathogenic bacteria have to cope with defence mechanisms mediated by adaptive and
innate immunity of the host cells. Cationic antimicrobial peptides (CAMPs)
represent one of the most effective components of the host innate immune
response. Here we establish the function of Lmo1695, a member of the VirR
dependent virulence regulon, recently identified in Listeria monocytogenes.
Lmo1695 encodes a membrane protein of 98 kDa with strong homology to the multiple
peptide resistance factor (MprF) of Staphylococcus aureus. Like staphylococcal
MprF, we found that Lmo1695 is involved in the synthesis of the membrane
phospholipid lysylphosphatidylglycerol (L-PG). In addition, Lmo1695 is also
essential for lysinylation of diphosphatidylglycerol (DPG), another phospholipid
widely distributed in bacterial membranes. A Deltalmo1695 mutant lacking the
lysinylated phospholipids was particularly susceptible to CAMPs of human and
bacterial origin. The mutant strain infected both epithelial cells and
macrophages only poorly and was attenuated for virulence when tested in a mouse
model of infection. Lmo1695 is a member of a growing list of survival factors
which enable growth of L. monocytogenes in different environments.
PMID- 17042785
TI - The exceptionally tight affinity of DnaA for ATP/ADP requires a unique aspartic
acid residue in the AAA+ sensor 1 motif.
AB - Escherichia coli DnaA, an AAA+ superfamily protein, initiates chromosomal
replication in an ATP-binding-dependent manner. Although DnaA has conserved
Walker A/B motifs, it binds adenine nucleotides 10- to 100-fold more tightly than
do many other AAA+ proteins. This study shows that the DnaA Asp-269 residue,
located in the sensor 1 motif, plays a specific role in supporting high-affinity
ATP/ADP binding. The affinity of the DnaA D269A mutant for ATP/ADP is at least 10
to 100-fold reduced compared with that of the wild-type and DnaA R270A proteins.
In contrast, the abilities of DnaA D269A to bind a typical DnaA box, unwind oriC
duplex in the presence of elevated concentrations of ATP, load DnaB onto DNA and
support minichromosomal replication in a reconstituted system are retained.
Whereas the acidic Asp residue is highly conserved among eubacterial DnaA
homologues, the corresponding residue in many other AAA+ proteins is Asn/Thr and
in some AAA+ proteins these neutral residues are essential for ATP hydrolysis but
not ATP binding. As the intrinsic ATPase activity of DnaA is extremely weak, this
study reveals a novel and specific function for the sensor 1 motif in tight
ATP/ADP binding, one that depends on the alternate key residue Asp.
PMID- 17042786
TI - Lex marks the spot: the virulent side of SOS and a closer look at the LexA
regulon.
AB - The SOS response that responds to DNA damage induces many genes that are under
LexA repression. A detailed examination of LexA regulons using genome-wide
techniques has recently been undertaken in both Escherichia coli and Bacillus
subtilis. These extensive and elegant studies have now charted the extent of the
LexA regulons, uncovered many new genes, and exposed a limited overlap in the
LexA regulon between the two bacteria. As more bacterial genomes are analysed,
more curiosities in LexA regulons arise. Several notable examples include the
discovery of a LexA-like protein, HdiR, in Lactococcus lactis, organisms with two
lexA genes, and small DNA damage-inducible cassettes under LexA control. In the
cyanobacterium Synechocystis, genetic and microarray studies demonstrated that a
LexA paralogue exerts control over an entirely different set of carbon-controlled
genes and is crucial to cells facing carbon starvation. An examination of SOS
induction evoked by common therapeutic drugs has shed new light on unsuspected
consequences of drug exposure. Certain antibiotics, most notably fluoroquinolones
such as ciprofloxacin, can induce an SOS response and can modulate the spread of
virulence factors and drug resistance. SOS induction by beta-lactams in E. coli
triggers a novel form of antibiotic defence that involves cell wall stress and
signal transduction by the DpiAB two-component system. In this review, we provide
an overview of these new directions in SOS and LexA research with emphasis on a
few themes: identification of genes under LexA control, the identification of new
endogenous triggers, and antibiotic-induced SOS response and its consequences.
PMID- 17042787
TI - Specificity of Streptococcus pyogenes NAD(+) glycohydrolase in cytolysin-mediated
translocation.
AB - The mechanism by which the cytolysin-mediated translocation (CMT) pathway of the
Gram-positive pathogen Streptococcus pyogenes injects effector proteins into the
cytosol of an infected host cell via the pore-forming protein streptolysin O is
unknown. Key questions include whether the pathway can discriminate between
different substrates for translocation, and whether the effector protein plays an
active or passive role in the translocation process. Here we show that CMT can
discriminate between a known effector of the pathway, the S. pyogenes NAD(+)
glycohydrolase (SPN), and a second secreted protein, the mitogenic factor (MF),
routing the former into the host cell cytosol and the latter into the
extracellular milieu. Residues within the amino-terminal 190 residues of SPN were
essential for discrimination, as deletions within this domain produced proteins
that retained full enzymatic activity, but were completely uncoupled from the
translocation pathway. The enzymatic domain itself played a pivotal role in the
discrimination as deletions within this domain also produced translocation
incompetent proteins and the conversion of MF to a translocation-competent form
required fusion with both SPN domains in a contiguous orientation. These data
establish that CMT is discriminatory, and that SPN is a multidomain protein that
plays an active role in its translocation.
PMID- 17042788
TI - Topoisomerases of kinetoplastid parasites: why so fascinating?
AB - DNA topoisomerases are the key enzymes involved in carrying out high precision
DNA transactions inside the cells. However, they are detrimental to the cell when
a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by
trapping the enzymes in covalent complexes on the DNA. The discovery of unusual
heterodimeric topoisomerase I in kinetoplastid family added a new twist in
topoisomerase research related to evolution, functional conservation and their
preferential sensitivity to Camptothecin. On the other hand, structural and
mechanistic studies on kinetoplastid topoisomerase II delineate some
distinguishing features that differentiate the parasitic enzyme from its
prokaryotic and eukaryotic counterparts. This review summarizes the recent
advances in research in kinetoplastid topoisomerases, their evolutionary
significance and the death of the unicellular parasite Leishmania donovani
induced by topoisomerase I inhibitor camptothecin.
PMID- 17042789
TI - Differential disinhibition of the neonatal hypothalamic- pituitary-adrenal axis
in brain-specific CRH receptor 1-knockout mice.
AB - In the adult, corticotropin-releasing hormone (CRH) is the key mediator for the
behavioural and neuroendocrine response to stress. It has also been hypothesized
that, during postnatal development of the stress system, CRH controls the
activity of the HPA axis and mediates the effects of early disturbances, e.g. 24
h of maternal deprivation. In the current study we investigated the function of
specific brain corticotropin-releasing hormone receptor type 1 (CRHR1)
subpopulations in the control of the HPA axis during postnatal development under
basal conditions as well as after 24 h of maternal deprivation. We used two
conditional CRHR1-deficient mouse lines which lack this receptor, either
specifically in forebrain and limbic structures (Cam-CRHR1) or in all neurons
(Nes-CRHR1). Basal circulating corticosterone was increased in Nes-CRHR1 mice
compared to controls. Corticosterone response to maternal deprivation was
significantly increased in both CRHR1-deficient lines. In the paraventricular
nucleus, Cam-CRHR1 animals displayed enhanced CRH and decreased vasopressin
expression levels. In contrast, gene expression in Nes-CRHR1 pups was strikingly
similar to that in maternally deprived control pups. Furthermore, maternal
deprivation resulted in an enhanced response of Cam-CRHR1 pups in the brain,
while expression levels in Nes-CRHR1 mouse pups were mostly unchanged. Our
results demonstrate that brainstem and/or hypothalamic CRHR1 contribute to the
suppression of basal corticosterone secretion in the neonate, while limbic and/or
forebrain CRHR1 dampen the activation of the neonatal HPA axis induced by
maternal deprivation.
PMID- 17042790
TI - Preferential responses in amygdala and insula during presentation of facial
contempt and disgust.
AB - Some authors consider contempt to be a basic emotion while others consider it a
variant of disgust. The neural correlates of contempt have not so far been
specifically contrasted with disgust. Using functional magnetic resonance imaging
(fMRI), we investigated the neural networks involved in the processing of facial
contempt and disgust in 24 healthy subjects. Facial recognition of contempt was
lower than that of disgust and of neutral faces. The imaging data indicated
significant activity in the amygdala and in globus pallidus and putamen during
processing of contemptuous faces. Bilateral insula and caudate nuclei and left as
well as right inferior frontal gyrus were engaged during processing of disgusted
faces. Moreover, direct comparisons of contempt vs. disgust yielded significantly
different activations in the amygdala. On the other hand, disgusted faces
elicited greater activation than contemptuous faces in the right insula and
caudate. Our findings suggest preferential involvement of different neural
substrates in the processing of facial emotional expressions of contempt and
disgust.
PMID- 17042791
TI - Depolarization-induced suppression of inhibition mediated by endocannabinoids at
synapses from fast-spiking interneurons to medium spiny neurons in the striatum.
AB - Endogenous cannabinoids (endocannabinoids) act as retrograde inhibitory
messengers in various regions of the brain. We have recently reported that
endocannabinoids mediate short-term retrograde suppression of excitatory synaptic
transmission from the neocortex to medium spiny (MS) neurons, the major
projection neurons from the striatum. However, it remains unclear whether
endocannabinoids modulate inhibitory transmission in the striatum. Here we show
that depolarization of MS neurons induces transient suppression of inhibition
that is mediated by retrograde endocannabinoid signalling. By paired recording
from a fast-spiking (FS) interneuron and an MS neuron, we demonstrated that FS-MS
inhibitory synapses undergo endocannabinoid-mediated retrograde suppression. We
verified that GABAergic inhibitory terminals immunopositive for parvalbumin (PV),
a marker for FS interneurons, expressed CB1 receptors. These PV-CB1 double
positive terminals surrounded dopamine D1 receptor-positive and D2 receptor
positive MS neurons; these constitute direct and indirect pathways, respectively.
These results suggest that endocannabinoid-mediated retrograde suppression of
inhibition influences information flow along both direct and indirect pathways,
depending on the activity of MS neurons.
PMID- 17042792
TI - Bottom-up, not top-down, modulation of imitation by human and robotic models.
AB - Visual observation of human actions provokes more motor activation than
observation of robotic actions. We investigated the extent to which this
visuomotor priming effect is mediated by bottom-up or top-down processing. The
bottom-up hypothesis suggests that robotic movements are less effective in
activating the 'mirror system' via pathways from visual areas via the superior
temporal sulcus to parietal and premotor cortices. The top-down hypothesis
postulates that beliefs about the animacy of a movement stimulus modulate mirror
system activity via descending pathways from areas such as the temporal pole and
prefrontal cortex. In an automatic imitation task, subjects performed a
prespecified movement (e.g. hand opening) on presentation of a human or robotic
hand making a compatible (opening) or incompatible (closing) movement. The speed
of responding on compatible trials, compared with incompatible trials, indexed
visuomotor priming. In the first experiment, robotic stimuli were constructed by
adding a metal and wire 'wrist' to a human hand. Questionnaire data indicated
that subjects believed these movements to be less animate than those of the human
stimuli but the visuomotor priming effects of the human and robotic stimuli did
not differ. In the second experiment, when the robotic stimuli were more angular
and symmetrical than the human stimuli, human movements elicited more visuomotor
priming than the robotic movements. However, the subjects' beliefs about the
animacy of the stimuli did not affect their performance. These results suggest
that bottom-up processing is primarily responsible for the visuomotor priming
advantage of human stimuli.
PMID- 17042793
TI - A distinct anatomical network of cortical areas for analysis of motion in far
peripheral vision.
AB - We defined cortical areas involved in the analysis of motion in the far
peripheral visual field, a poorly understood aspect of visual processing in
primates. This was accomplished by small tracer injections within and around the
representations of the monocular field of vision ('temporal crescents') in the
middle temporal area (MT) of marmoset monkeys. Quantitative analyses demonstrate
that the representation of the far periphery receives specific connections from
the retrosplenial cortex (areas 23v and prostriata), as well as comparatively
stronger inputs from the primary visual area (V1) and from areas surrounding MT
(in particular, the medial superior temporal area, MST). In contrast, the far
peripheral representation receives little or no input from most other
extrastriate areas, including the second visual area (V2), the densely myelinated
areas of the dorsomedial cortex, and ventral stream areas; these areas are shown
to have robust projections to other parts of MT. Our results demonstrate that the
responses of cells in different parts of a same visual area can be determined by
different combinations of synaptic inputs, in terms of areas of origin. They also
suggest that the interconnections responsible for motion processing in the far
periphery of the visual field convey information that is crucial for rapid
response aspects of visual function such as orienting, postural and defensive
reactions.
PMID- 17042794
TI - Zinc neurotoxicity is dependent on intracellular NAD levels and the sirtuin
pathway.
AB - Zinc neurotoxicity has been demonstrated in ischemic, seizure, hypoglycemic, and
trauma-induced neuronal death where Zn(2+) is thought to be synaptically released
and taken up in neighbouring neurons, reaching toxic concentrations. We
previously demonstrated that toxicity of extracellular Zn(2+) depended on entry,
elevation in intracellular free Zn(2+) ([Zn(2+)](i)), a reduction in NAD(+) and
ATP levels, and dysfunction of glycolysis and cellular metabolism. We suggested
that PARP-1 activation alone can not explain this loss of neuronal NAD(+). NAD(+)
was recently demonstrated to permeate neurons and glia, and we have now shown
that exogenous NAD(+) can reduce Zn(2+) neurotoxicity, and 3-acetylpyridine,
which generates inactive NAD(+), potentiated Zn(2+) neurotoxicity. Sirtinol and 2
hydroxynaphthaldehyde, inhibitors of the sirtuin pathway (SIRT proteins are
NAD(+)-catabolic protein deacetylases), attenuated both acute and chronic Zn(2+)
neurotoxicity. Resveratrol and fisetin (sirtuin activators) potentiated NAD(+)
loss and Zn(2+) neurotoxicities. Furthermore, neuronal cultures derived from the
Wld(s) mouse, which overexpress the NAD(+) synthetic enzyme nicotinamide
mononucleotide adenyl transferase (NMNAT-1), had reduced sensitivity to Zn(2+)
neurotoxicity. Finally, nicotinamide was demonstrated to attenuate CA1 neuronal
death after 10 min of global ischemia in rat even if administered 1 h after the
insult. Together with previous data, these results further implicate NAD(+)
levels in Zn(2+) neurotoxicity.
PMID- 17042795
TI - An in vivo analysis of Schwann cell programmed cell death in embryonic mice: the
role of axons, glial growth factor, and the pro-apoptotic gene Bax.
AB - Building upon previous in vitro studies, the present investigation involves an in
vivo examination of Schwann cell programmed cell death (PCD) and development in
the brachial spinal ventral roots of embryonic mice. The period of Schwann cell
PCD was found to occur between embryonic days (E) 11.5 and 18.5, which is in
close coincidence with the PCD period of associated brachial motoneurons (E13.5
E18.5). Additionally, Schwann cells exhibited a peak in proliferation at E11.5,
and differentiation from the precursor to the immature Schwann cell stage between
E12.5 and E14.5. Axon-mediated Schwann cell survival was demonstrated in vivo by
excitotoxic elimination of motoneurons and their axons, via NMDA treatment in
utero. This treatment increased apoptotic Schwann cell death within degenerating
ventral roots. Conversely, in utero co-treatment of glial growth factor (GGF)
with NMDA resulted in decreased Schwann cell death, a finding which supports
previous reports of the promotion of Schwann cell survival by GGF. Analysis of
mice lacking Bax, a pro-apoptotic Bcl-2 protein, revealed that Schwann cell PCD
occurred independently of Bax. However, owing to the lack of motoneuron PCD in
Bax-knockout mice, and the corresponding increase in the number of ventral root
axons, a decrease in Schwann cell PCD was observed during the normal period of
motoneuron PCD. In conclusion, our findings regarding the regulation of Schwann
cell development in vivo are consistent with the conclusions from in vitro
studies, including a dependency on axons for survival and proliferation signals,
timing of differentiation, and a dependency on GGF.
PMID- 17042796
TI - Lesion of the pedunculopontine nucleus reverses hyperactivity of the subthalamic
nucleus and substantia nigra pars reticulata in a 6-hydroxydopamine rat model.
AB - The pedunculopontine nucleus (PPN) and the subthalamic nucleus (STN) are
reciprocally connected by excitatory projections. In the 6-hydroxydopamine (6
OHDA) rat model the PPN was found to be hyperactive. Similarly, the STN and the
substantia nigra pars reticulata (SNr) showed increased activity in Parkinson's
disease (PD) animal models. A lesion of the STN was shown to restore increased
activity levels in the SNr of 6-OHDA-treated rats. As the STN and the PPN were
reciprocally connected by excitatory projections and both structures were shown
to be hyperactive in PD animal models, the present study was performed in order
to investigate the changes in neuronal activity of the STN and SNr under urethane
anesthesia after unilateral ibotenic acid lesioning of the PPN in animals with
previous unilateral 6-OHDA lesions of the substantia nigra pars compacta (SNc).
The firing rate of STN neurons significantly increased from 10.3 +/- 0.6 spikes/s
(mean +/- SEM) to 17.8 +/- 1.8 spikes/s after SNc lesion and returned to normal
levels of 10.8 +/- 0.7 spikes/s after additional lesion of the PPN. Similarly,
the firing rate of SNr neurons significantly increased from 19.0 +/- 1.1 to 25.9
+/- 1.4 spikes/s after SNc lesion, the hyperactivity being reversed after
additional PPN lesion to 16.8 +/- 1.2 spikes/s. The reversal of STN and SNr
hyperactivity of 6-OHDA-treated rats by additional PPN lesion suggests an
important modulatory influence of the PPN on STN activity. Moreover, these
findings could indicate a new therapeutic strategy in PD by interventional
modulation of the PPN.
PMID- 17042797
TI - Stereological methods reveal the robust size and stability of ectopic hilar
granule cells after pilocarpine-induced status epilepticus in the adult rat.
AB - Following status epilepticus in the rat, dentate granule cell neurogenesis
increases greatly, and many of the new neurons appear to develop ectopically, in
the hilar region of the hippocampal formation. It has been suggested that the
ectopic hilar granule cells could contribute to the spontaneous seizures that
ultimately develop after status epilepticus. However, the population has never
been quantified, so it is unclear whether it is substantial enough to have a
strong influence on epileptogenesis. To quantify this population, the total
number of ectopic hilar granule cells was estimated using unbiased stereology at
different times after pilocarpine-induced status epilepticus. The number of hilar
neurons immunoreactive for Prox-1, a granule-cell-specific marker, was estimated
using the optical fractionator method. The results indicate that the size of the
hilar ectopic granule cell population after status epilepticus is substantial,
and stable over time. Interestingly, the size of the population appears to be
correlated with the frequency of behavioral seizures, because animals with more
ectopic granule cells in the hilus have more frequent behavioral seizures. The
hilar ectopic granule cell population does not appear to vary systematically
across the septotemporal axis, although it is associated with an increase in
volume of the hilus. The results provide new insight into the potential role of
ectopic hilar granule cells in the pilocarpine model of temporal lobe epilepsy.
PMID- 17042798
TI - Early postnatal changes in respiratory activity in rat in vitro and modulatory
effects of substance P.
AB - Developmental changes in the respiratory activity and its modulation by substance
P (SP) were studied in the neonatal rat brainstem-spinal cord preparation from
the day of birth to day 3 (P0-P3). The respiratory network activity in the
ventrolateral medulla was represented by two types of bursts: basic regular
bursts with typical decrementing shape and biphasic bursts appearing after
augmented biphasic discharges in inspiratory neurons. With advancing postnatal
age the respiratory output was considerably modified; the basic rhythm became
faster by 20%, whereas the biphasic burst rate, which was originally 15 times
slower, declined further by 180% and the C4 burst duration significantly
decreased by 20% due to reduced decay time without preceding changes in the
central inspiratory drive. SP had an age-dependent excitatory effect on
respiratory activity. In the basic rhythm, SP could induce transient rhythm
cessations on P0-P2 but not on P3. For the biphasic burst frequency, the
sensitivity to SP significantly decreased from P0 to P3, whereas the range of SP
induced changes increased. In both types of bursts, SP prolonged C4 burst
duration due to increasing decay time. This effect was three times greater on P3
and did not depend on the central inspiratory drive. Our results suggest that the
potency of SP to regulate the respiratory activity elevates during the early
postnatal period. The developmental changes in the respiratory activity appear to
represent the transient stage in the maturation of rhythm and pattern generation
mechanisms facilitating adaptive behavior of a quickly growing organism.
PMID- 17042800
TI - Quality of care, health system errors, and nurses.
PMID- 17042801
TI - Safety in health care today: more than just freedom from errors and accidents?
PMID- 17042799
TI - Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway
inflammation in a murine model of asthma.
AB - A number of epidemiological and clinical studies have suggested an inverse
association between allergy and helminth infection, such as Schistosomiasis.
Therefore, we hypothesize that Schistosoma japonicum egg antigens, a type of
native antigen, can induce production of CD4(+) CD25(+) T cells with regulatory
activity, modulating airway inflammation and inhibiting asthma development. The
frequency of CD4(+) CD25(+) T cells was determined by flow cytometry for mice
treated with ovalbumin (OVA), CD25(+) depletion/OVA, schistosome egg antigens,
schistosome egg antigens/OVA and for control mice. The ability of CD25(+) T cells
from these mice to suppress T-cell proliferation and cytokine production was
investigated both in vivo and in vitro. Results showed that the CD4(+) CD25(+) T
cells of OVA-treated mice exhibited impaired control of dysregulated mucosal T
helper 2 responses compared to the controls (P < 0.05). Depletion of CD25(+)
cells accelerated OVA-induced airway inflammation and increased the expression of
interleukin (IL)-5 and IL-4. Treatment with schistosome egg antigens increased
the number and suppressive activity of CD4(+) CD25(+) T cells, which made IL-10,
but little IL-4. In a murine model of asthma, S. japonicum egg antigens decreased
the expression of Th2 cytokines, relieved antigen-induced airway inflammation,
and inhibited asthma development. Thus, we provided evidence that S. japonicum
egg antigens induced the production of CD4(+) CD25(+) T cells, resulting in
constitutive immunosuppressive activity and inhibition of asthma development.
These results reveal a novel form of protection against asthma and suggest a
mechanistic explanation for the protective effect of helminth infection on the
development of allergy.
PMID- 17042802
TI - Recognizing and reporting child physical abuse: a survey of primary healthcare
professionals.
AB - AIM: This paper reports a study of the self-reported ability and behaviours of
primary healthcare professionals in Northern Ireland to recognise child physical
abuse. A secondary aim was to assess the educational and training needs of these
professionals. BACKGROUND: In the United Kingdom, 7% of children suffer serious
physical abuse by a parent or carer, and two children aged under 15 years die
from abuse each week. Recognizing child physical abuse depends on the knowledge
and skills of a variety of healthcare professionals. METHODS: A stratified random
sample of 979 nurses, doctors, and dentists working in primary care in Northern
Ireland were sent a postal questionnaire; 419 responded, giving a 43% response
rate. The data were collected in 2002-2003. FINDINGS: In their working lives 60%
(251) said that they had seen a suspicious child physical abuse case; however,
only 47% (201) had reported a suspicious case to the authorities, leaving a 13%
gap in reporting. Although 74% (310) of respondents were aware of some of the
mechanisms for reporting child physical abuse, 79% (332) requested further
education on this topic. Ability to recognize and willingness to report abuse
cases discriminated between the three professional groups. Compared with doctors
or dentists, community nurses were statistically significantly more likely to
recognize and report suspicions of child physical abuse, and were the group most
aware of child abuse issues and the most willing to become involved in abuse
cases. CONCLUSIONS: The findings suggest that professional fears and anxieties
and lack of knowledge act as barriers to recognizing and reporting abuse and that
more specific education and support for primary care professionals is required.
PMID- 17042803
TI - Care of patients with chronic obstructive pulmonary disease in primary health
care.
AB - AIM: This paper is a report of a study of nurses' perceptions of caring for
patients with chronic obstructive pulmonary disease. BACKGROUND: Chronic
obstructive pulmonary disease is a global health problem and the number of
patients being treated with this disease in primary healthcare settings is
increasing. This places new demands on the nurses involved. METHOD: A
phenomenographic approach was adopted, using a purposive sample. Data were
generated between February and May 2003 from 20 interviews with district nurses
and general nurses who cared for patients in primary healthcare settings with
chronic obstructive pulmonary disease. FINDINGS: In most cases, nurses cared for
older people with moderate to severe chronic obstructive pulmonary disease. They
described this care from two overall orientations: task and individual. The
nurses' perceptions of the care of these patients were described as creating
commitment and participation by establishing a good relationship with patients
and supporting them in their personal care, educating patients by supplying
information and knowledge in various ways, co-operation by co-operating with or
referring to other caregivers, and arranging and implementing clinical
examinations and treatments. CONCLUSION: The type of care depended on who the
patient met: either a task-oriented nurse or an individual-oriented nurse.
Therefore, nursing programmes should pay special attention to the support and
guidance of new and inexperienced and task-oriented nurses. Healthcare planners
should take into consideration the need for individualized care when organizing
care and allocating resources for chronically ill people.
PMID- 17042804
TI - Health preferences and decision-making needs of disadvantaged women.
AB - AIM: This paper reports the results of a survey of disadvantaged women in La
Pintana, a municipality of Santiago, Chile, to determine their health decision
making needs. BACKGROUND: Research is needed as there is no published community
based study focusing specifically on health decision-making needs of
disadvantaged women. METHODS: From April to November 1999, we conducted a cross
sectional interview survey of women registered at primary healthcare centres in
La Pintana, an impoverished municipality of Santiago, Chile. RESULTS: The survey
participants were 554 adult women over 15 years of age. Seventy-five percent
reported making current health-related decisions. Types of decisions were
primarily about navigation: where, when and from whom to seek care. The most
common role in decision-making was sharing the decision with others, specifically
husbands and other family members. Fifty-four percent experienced decisional
conflict or uncertainty about options. Those reporting more manifestations of
decisional conflict were more likely to lack information on available options,
pros and cons of the options, and chances of benefits and harms associated with
the options; they were also more likely to be unclear about what was important to
them, to feel pressure from others, lack skill or ability in decision-making and
be older. The most common strategies used when making all types of decisions were
obtaining information on options and recommendations, and getting support from
others. Participants preferred to receive information about options through
counselling from their physicians, rather than nurses, from printed materials and
from discussion groups of people facing the same decision. CONCLUSION: The
majority of disadvantaged women were actively involved in decision-making and
needed decision support to navigate the healthcare system. Nurses should play a
more pivotal role in providing health decision support. This study needs to be
replicated in other countries and cultural contexts.
PMID- 17042805
TI - Living in the shadow of fear: adolescents' lived experience of depression.
AB - AIM: This paper reports a phenomenological study whose aim was to gain an
understanding of what it was like to be an adolescent living with depression.
BACKGROUND: Depression is a significant mental health problem among adolescents.
Identifying the meanings that adolescents assign to their experiences with
depression is needed in order to develop interventions that will improve their
care and quality of life. METHOD: The study took place in a city in Western
Canada. Fourteen adolescents (13.5 to 18 years) diagnosed with depression
participated in individual open-ended interviews and focus group interviews
between July 2001 and June 2002. Field notes were recorded. Thematic statements
that were representative of the adolescents' lived experience were isolated from
the interviews and field notes. Using all the phrases, sentence clusters and
field notes, the data were then reduced until essential and incidental themes
emerged. FINDINGS: "Living in the shadow of fear" emerged as the essence of the
adolescents' experiences and ultimately defined what it was like to live with
depression. The shadow of fear was associated not only with fear of a return of
the "bad" feelings related to their depression, but also to fear of not getting
help, not surviving the "bad" feelings, and fear of having to do all the "hard
work" in overcoming the "bad" feelings. This essence was supported by four
themes: "containing the shadow of fear", "keeping the self alive", "maintaining a
sense of belonging in the world" and "feeling valued as a human being".
CONCLUSIONS: Adolescents with depression need adequate resources and support
throughout the illness trajectory, including those periods when their depression
is under control.
PMID- 17042806
TI - Percutaneous endoscopic gastrostomies: the burden of treatment from a patient
perspective.
AB - AIM: This paper reports a study of patients' experiences of this relatively new
technology, and explores possible strategies for defining, delineating and
addressing patients' concerns, problems and needs. BACKGROUND: The number of
patients in the community relying on percutaneous endoscopic gastrostomy for
their nutritional needs is increasing, but percutaneous endoscopic gastrostomy
feeding is not problem-free. However, few studies report on its impact from a
patient perspective. METHODS: Twenty adults with long-term percutaneous
endoscopic gastrostomies were interviewed in their own homes, using both semi
structured and structured approaches. Qualitative data were analysed thematically
and related to a symptom checklist and an established quality of life measure,
the Short Form-12. FINDINGS: Most participants felt that insertion of a
percutaneous endoscopic gastrostomy had been life-saving, but found that
percutaneous endoscopic gastrostomy feeding came to dominate their lives and was
associated with an appreciable "burden of treatment". Some, but not all, of the
problems recounted were unavoidable: percutaneous endoscopic gastrostomy feeding
inevitably imposed physical restrictions on mobility; 17/20 participants had
experienced serious technical problems with their percutaneous endoscopic
gastrostomy tubes. On structured questioning, all interviewees had some,
potentially treatable, gastrointestinal symptoms, and eight had continuous
problems. In some cases, the burden of treatment was exaggerated by being
unanticipated and, for 13 patients, difficulties with care provided by non
specialist services. Describing this "burden of treatment" for each patient
required both a narrative and a structured approach: without the symptom
checklists, some important and treatable problems were missed. Both physical and
mental health Short Form-12 scores were low, and mental health scores were
congruent with the interview data. CONCLUSIONS: It might be possible to reduce
the "burden of treatment" identified by incorporating a structured approach to
patient monitoring and by reviewing the occupational territories of specialist
and non-specialist practitioners. Further research with larger numbers of
participants is needed to explore the integration of narrative and quantitative
data when determining patients' clinical needs.
PMID- 17042807
TI - Factors contributing to frailty: literature review.
AB - AIM: This paper presents a review of theoretical and research literature in order
to identify the factors contributing to frailty. BACKGROUND: Frailty is a
multifaceted gerontological concept that lacks a clear definition, but may result
from an identifiable homogeneous cluster of bio-psycho-social-spiritual factors.
METHOD: A total of 134 articles were identified through a search of the MEDLINE
(1966 to July 2004), CINAHL (1982 to July 2004), PsychInfo (1985 to July 2004)
and Ageline (1995 to July 2004) databases. Each article was reviewed to determine
its fit with inclusion/exclusion criteria. Seven research and 11 theoretical
articles were retained and further reviewed for methodological quality using a
validity tool. FINDINGS: Seventeen different definitions of frailty were
identified. Regardless of the differing definitions, common contributing factors
could be identified. Physical, cognitive/psychological, nutritional and social
factors, as well as ageing and disease, were evident in both the theoretical and
research literature. CONCLUSIONS: Although there is strong agreement that a
relationship exists between a cluster of factors and frailty, designation of the
factors as contributors or outcomes of frailty differs. Without a clear
explanatory theory of the path from contributors to frailty to outcomes, research
will continue to produce confusing results. A theoretical framework that includes
bio-psycho-social-spiritual factors as contributors to frailty is recommended as
the most useful framework for gerontological nursing.
PMID- 17042808
TI - Developing an advanced nurse practitioner service in emergency care: attitudes of
nurses and doctors.
AB - AIM: This paper reports a study to determine the attitudes of nurses, doctors and
general medical practitioners towards the development of an advanced nurse
practitioner service within an emergency department. BACKGROUND: The role of
advanced nurse practitioner in emergency care has emerged in a number of
countries, and has brought with it confusion about titles, role boundaries,
clinical accountability and educational requirements. Initially, the role
resulted from a need for healthcare professionals to provide a service to the
increased numbers of patients presenting to hospital with less urgent problems.
Since then, the service has evolved to one where nurse practitioners provide high
quality and cost-effective care to persons who seek help for non-urgent, urgent
or emergent conditions in a variety of emergency care settings. However, little
research could be identified on the attitudes of relevant nursing and medical
staff towards the development of this role. METHODS: A questionnaire survey was
carried out, and a 29-item Likert rating scale was developed to measure
attitudes. Along with some demographic variables, two open-ended questions were
added to allow respondents to elaborate on what they perceived as benefits and
difficulties associated with an advanced nurse practitioner service. All general
practitioners, emergency nurses and emergency doctors in one health board in the
Republic of Ireland were targeted, and 25 emergency nurses, 13 emergency doctors
and 69 general practitioners were approached to take part. Data were collected in
February 2004. FINDINGS: An overall response rate of 74.8% was achieved. All
respondents were positive towards the development of an advanced nurse
practitioner service, with general practitioners being less positive. The
principal differences appeared between general practitioners and hospital
emergency care staff. CONCLUSION: There is a need for a multidisciplinary
approach to the planning of advanced nurse practitioner services. To achieve
multiprofessional acceptance, an accredited and standardized education programme
is required, and this must address existing role boundaries.
PMID- 17042809
TI - Developing nursing and midwifery research capacity in a university department:
case study.
AB - AIM: This paper reports a case study which examined the selection, implementation
and outcomes of one university department's approach to building research
capacity in nursing and midwifery. BACKGROUND: The literature identifies building
nursing research capacity as an important challenge. In countries such as
Australia and the United Kingdom it is taking place in the context of the move of
nurse education into the university sector. Structural and cultural barriers to
building academic nursing research capacity exist. Previous studies highlight the
strategies that academic departments adopt to build nursing research capacity.
METHODS: Using case study methodology, data were collected using documentary
analysis and semi-structured interviews with a purposive sample of 27 academic
and related staff and a focus group with seven staff. The data were collected
between 2003 and 2005. FINDINGS: The department had adopted an inclusive approach
to capacity development (allowing all teaching staff to develop their research
capability), but is now moving towards a more focused path and the cultivation of
"leading edge" research. Neophyte researchers described lacking confidence in
undertaking research, and expressed a need for more formal support structures.
The importance of effective management of capacity building was highlighted,
including transparent communication and mapping of existing capacity. Key
external influences included the lack of core research funding, and divergence
between the university's emphasis on research and the department's desire to
develop an interface between teaching, research and clinical practice.
CONCLUSION: Academic leadership and educational management should work in tandem.
Staff development and the provision of time and support are crucial aspects of
research capacity development. The effectiveness of "inclusive" and "exclusive"
approaches to research capacity development depends on the nature of each
department, and they are not mutually exclusive.
PMID- 17042810
TI - A revision of a job evaluation system.
AB - AIMS: This paper reports a revision of the United Kingdom's National Health
Service Job Evaluation System and tests the revised system in eight clinical
nursing management jobs in four Turkish hospitals. BACKGROUND: A job evaluation
system was developed in the United Kingdom in 2003-2004. Most studies have
focused on how the whole system will be implemented in a health organization. No
study investigating proficiency of the system in terms of factors and their level
definitions was found. METHODS: The factors Knowledge, Training and experience
and Working conditions were divided into five factors: Knowledge, Experience,
Education, Environmental conditions and Hazards. To test the revised system, all
the nursing management jobs in four hospitals were evaluated using a factor-based
questionnaire including nurses' demographic information and 19 variables. The
questionnaire was distributed to 57 supervisor nurses in 31 clinics at four
hospitals in one Turkish city in 2005. All the questionnaires were analysed to
evaluate the jobs. RESULTS: The job scores change depending on clinical
conditions. Although the score range in the National Health Service Job
Evaluation system has been determined as 405-465 points (band VI) for Nurse team
leader and 469-536 points (band VII) for Nurse team manager jobs, the job scores
in the present study were 363 (band V) - 557 points (band VIIIa) and 379 (band V)
- 586 points (band VIIIa) respectively. CONCLUSION: Although this exploratory
study was limited to four hospitals in one city in Turkey, the results indicated
that two new jobs would be identified in the National Health Service system to
match the jobs in the intensive care and emergency units.
PMID- 17042811
TI - Rules and resources: a structuration approach to understanding the coordination
of children's inpatient health care.
AB - AIM: This paper presents findings from a multi-method study exploring the process
of care coordination in children's inpatient health care. BACKGROUND: Existing
work on care coordination is typified by "black-box" type studies that measure
inputs to and outcomes of care coordination roles and practices, without
addressing the process of coordination. METHOD: Using questionnaires, interviews
and observation to collect data in multiple sites in the United Kingdom and
Denmark between 1999 and 2005, the study gathered the perceptions of staff and
compared these with observed practice. Giddens' structuration theory was used to
provide an analytical and explanatory framework. FINDINGS: Current care
coordination practice is diverse and inconsistent. It involves a wide range of
clinical and non-clinical staff, many of whom perceive a lack of clarity about
who should perform specific coordination activities. Staff draw upon a wide range
of different material and non-material resources in coordinating care, the use of
which is governed by largely tacit and informal rules. CONCLUSIONS: Care
coordination can be usefully conceptualized as a "structurated" process--one that
is continually produced and reproduced by staff using rules and resources to
"instantiate" or bring about care coordination through action. Potentially
negative implications of this are manifested in diversity and inconsistency in
care coordination practice. However, positive aspects such as the opportunity
this provides to tailor care to the needs of the individual patient can be
realized.
PMID- 17042814
TI - Patient stories of living with a pressure ulcer.
AB - AIM: This paper reports the findings of a pilot study exploring the experience of
older people living with pressure ulcers. BACKGROUND: Pressure ulcers are known
to be a significant health burden, but little is known of the impact on the
quality of life of the sufferer. They mainly affect older people, and this is a
neglected group in previous studies of this topic. METHODS: A Heideggerian
phenomenological approach was used and patients were recruited if they were over
65 years of age and had a grade 3 or 4 pressure ulcer that had been present for
more than a month. Patients were recruited from multiple centres but the data
were analysed centrally. The study took place in 2003-2004. FINDINGS: Analysis of
the transcripts revealed three main themes, all with associated subthemes:
pressure ulcers produce endless pain; pressure ulcers produce a restricted life;
coping with a pressure ulcer. The endless pain theme had four subthemes: constant
presence, keeping still, equipment pain and treatment pain. Some patients found
that keeping still reduced their pain. Several patients also reported that pain
was exacerbated by their pressure relieving equipment and at dressing change.
There were three subthemes for the restricted life theme: impact on self, impact
on others and consequences. Patients found that the pressure ulcer restricted
their activities and had an impact on their families. In addition, for some, the
restrictions delayed their rehabilitation. To cope with their pressure ulcers,
patients developed ways of accepting their situation or comparing themselves with
others. CONCLUSIONS: Although a pilot, this study has produced a wealth of data
that demonstrates the impact of pressure ulcers on people. While a larger study
is required to obtain a European perspective, it is still reasonable to conclude
that the issues of pain and restrictions should be considered in the development
of pressure ulcer treatment and prevention guidelines.
PMID- 17042815
TI - Service users' experiences of 'as needed' psychotropic medications in acute
mental healthcare settings.
AB - AIMS: This paper reports a study which aimed to explore service users' views and
experiences of the processes associated with the prescription and administration
of 'as needed' (p.r.n.) psychotropic medications in acute mental health settings.
BACKGROUND: Few studies have explored the use of 'as needed' medication in acute
mental healthcare settings. Such medication is frequently requested by service
users, but the literature is unclear about the reasons for these requests or
service users' experiences of this treatment. METHOD: A convenience sample of 22
inpatients participated in face-to-face semi-structured interviews exploring
their treatment experiences of 'as needed' psychotropic medication in acute
mental health settings in a large city in the United Kingdom in 2005. Thematic
content analysis was carried out. RESULTS: Interviewees highlighted the value of
'as needed' medications. However, the process associated with their use was
perceived as confusing and stigmatizing. Service users had limited understanding
of and felt unsupported in attempts to use alternatives approaches. Additionally,
the decision-making and information-giving processes were unclear to them, which
raises issues of power and control in acute mental health settings. CONCLUSIONS:
Nurses should take account of the issues of power and control when administering
'as needed' medication. The provision of adequate treatment information should be
a priority to enable informed choices to be made about this form of medication.
PMID- 17042816
TI - Hope promoting strategies of Registered Nurses.
AB - AIM: This paper describes self-reported hope-promoting strategies used by
Registered Nurses whilst providing care for older patients in acute and long-term
care settings. BACKGROUND: The literature is replete with claims that Registered
Nurses engage in hope facilitation with their patients. However, these claims are
largely conjecture, with few studies empirically identifying the extent to which
Registered Nurses use hope interventions with their patients. Further, some
authors have questioned whether nurses have the necessary skills to undertake
this vital aspect of care. METHODS: In this Gadamerian hermeneutic
phenomenological study, undertaken in 2003 in Australia, we used in-depth
audiotaped interviews to collect data with 14 Registered Nurses. The interviews
were transcribed verbatim and analysed using the Turner method. FINDINGS: Whilst
participants clearly reported that they engaged in hope facilitation with older
patients, there were differences between the reported strategies used by
Registered Nurses in acute and long-term care settings. Further, the strategies
reported were not unique to hope promotion and have been variously described in
the literature on caring, presencing, holistic nursing and therapeutic nursing.
CONCLUSION: It is clear that participants considered hope promotion to be a vital
aspect of their care. However, the strategies that they reported were limited and
not inclusive of many and varied suggestions emerging from published studies on
hope promotion. Therefore, we recommend that nursing curricula, professional
development and in-service education programmes place hope facilitation on their
agenda and foster a culture in which promoting hope is seen as a vital aspect of
nursing care.
PMID- 17042817
TI - Heterosexual assumptions in verbal and non-verbal communication in nursing.
AB - AIM: This paper reports a study of what lesbian women and gay men had to say, as
patients and as partners, about their experiences of nursing in hospital care,
and what they regarded as important to communicate about homosexuality and
nursing. BACKGROUND: The social life of heterosexual cultures is based on the
assumption that all people are heterosexual, thereby making homosexuality
socially invisible. Nurses may assume that all patients and significant others
are heterosexual, and these heteronormative assumptions may lead to poor
communication that affects nursing quality by leading nurses to ask the wrong
questions and make incorrect judgements. METHOD: A qualitative interview study
was carried out in the spring of 2004. Seventeen women and 10 men ranging in age
from 23 to 65 years from different parts of Sweden participated. They described
46 experiences as patients and 31 as partners. FINDINGS: Heteronormativity was
communicated in waiting rooms, in patient documents and when registering for
admission, and nursing staff sometimes showed perplexity when an informant
deviated from this heteronormative assumption. Informants had often met nursing
staff who showed fear of behaving incorrectly, which could lead to a sense of
insecurity, thereby impeding further communication. As partners of gay patients,
informants felt that they had to deal with heterosexual assumptions more than
they did when they were patients, and the consequences were feelings of not being
accepted as a 'true' relative, of exclusion and neglect. Almost all participants
offered recommendations about how nursing staff could facilitate communication.
CONCLUSION: Heterosexual norms communicated unconsciously by nursing staff
contribute to ambivalent attitudes and feelings of insecurity that prevent
communication and easily lead to misconceptions. Educational and management
interventions, as well as increased communication, could make gay people more
visible and thereby encourage openness and awareness by hospital staff of the
norms that they communicate through their language and behaviour.
PMID- 17042818
TI - Stressors and coping of in-hospital haemodialysis patients aged 65 years and
over.
AB - AIMS: This paper reports a study to identify the types of stressors experienced
by in-hospital haemodialysis patients aged 65 years and older, and the use and
perceived helpfulness of coping strategies to manage these stressors. BACKGROUND:
Chronic renal failure and its treatments impose a variety of physical and
psychosocial stressors, which challenge patients. Although the stressors and
coping strategies of patients having dialysis treatment have been investigated,
no study has specifically focused on older adults. Such investigation is
important as the incidence of chronic kidney disease is increasing in this age
group. METHOD: In this descriptive, correlational study, the Haemodialysis
Stressor Scale and Jalowiec Coping Scale were used to investigate stressors and
coping strategies reported by 50 in-hospital haemodialysis patients aged 65 years
and older. The data were collected in Canada in 2004. RESULTS: Similar to
previous research, the stressors of fatigue and fluid restrictions ranked highly
as stressors in this sample. However, interference with social and recreational
activities were stressors unique to this group. Findings challenge some common
beliefs about haemodialysis patients. It is commonly believed that these patients
'get used to' haemodialysis, and therefore the number and troublesomeness of
stressors decrease over time. This belief was not supported because length of
time on haemodialysis did not affect participants' appraisal of stressors.
Another major finding was that older participants in this sample reported the use
of fewer coping strategies and found them less helpful. CONCLUSION: Further
research is needed to investigate factors affecting the stressors and coping
responses of older haemodialysis patients and to determine their impact on health
outcomes. Such knowledge will assist nurses in developing age-appropriate
strategies for promoting optimum wellness for these patients who will likely
spend the remainder of their life adhering to the regimen of haemodialysis.
PMID- 17042819
TI - Health and quality of life of ventilator-dependent children.
AB - AIM: This paper reports a qualitative study with ventilator-dependent children
and their parents, describing their experiences and meanings concerning the
children's health and quality of life. BACKGROUND: Recent medical advances have
enabled children to survive premature birth, congenital anomalies, critical
illness and accidents with long-term use of mechanical ventilation to support
breathing. In economically developed countries, the number of ventilator
dependent children is increasing and many require nurse-led home healthcare
services. Debate has been polarized as to whether life on a ventilator is in the
best interests of all children. The perspectives of ventilator-dependent children
are largely absent in the literature. METHODS: Principles derived from
Heideggerian phenomenology were used to describe how children and their parents
interpreted and rationalized the quality of the child's 'ventilator-dependent'
life and their health. The study had two phases with data collection commencing
in 1998 and completed in 2004. RESULTS: The participants were 35 ventilator
dependent children, and 50 mothers and 17 fathers of 53 children. Emergent themes
revealed some common features across this heterogeneous group. Ventilation made
the children feel better and if they had sufficient breath, they experienced
better quality of life. It was not possible to delineate the magnitude of health
gain or benefit, especially amongst preverbal children and those with profound
sensory impairments. Quality of life equated to quality of life experiences, but
some children experienced negative social impacts and low self-esteem. Home
healthcare services were not designed to bring about the desired social outcomes
that children identified. Parent's accounts showed subtle more negative
differences. CONCLUSION: The acceptance of children's dependence on machines to
live has brought about the need for nursing, medical, social and biological
boundaries to be redefined, especially around children's meanings of their
health, what they understand to be good quality of life, and what they need to
achieve it. Flexible, high quality child-focused homecare is likely to improve
children's outcomes.
PMID- 17042820
TI - Nursing is different than medicine: ethical difficulties in the process of care
in surgical units.
AB - AIM: This paper describes a study of the kinds of ethical difficulties nurses
face in the process of care in surgical units. BACKGROUND: Nurses face ethically
difficult situations in trying to find the most appropriate actions to take for
patients. Differences of opinion with doctors about the treatment and care of
patients and conflicts between nurses' value systems and those in the
organization where they are employed are described as sources of ethical
difficulty. Nurses experience moral distress when institutional constraints
restrict them from carrying out appropriate moral actions. METHODS: Ten female
nurses working in surgical units at one university hospital in Norway were
interviewed as part of a comprehensive investigation into the narratives of
nurses and doctors about being in ethically difficult situations. The transcribed
interview texts were subjected to a phenomenological-hermeneutic interpretation.
The study was conducted during 2004. FINDINGS: The main ethically difficult care
situations described by the nurses concerned being open and honest, trusting
patients' complaints, and creating limits to their involvement. Differences in
opinion with doctors about the treatments, the absence of doctors in the unit and
limited interest in holistic treatment and care resulted in nurses not receiving
the medical orders they needed. A heavy workload, lack of time and staffing
problems resulted in difficult ethical prioritizations and reduced standards of
care. Shared rooms and beds in the corridors made it difficult to preserve
patients' rights to privacy and confidentiality. CONCLUSION: Interventions and
investments are needed to improve the work environment of nurses, especially
modifying the job constraints of the work environment. The moral responsibility
for upholding the quality of care in surgical services and hospital performance
should be more equally distributed between nurses, doctors and hospital managers.
Discussions and collaboration between and within healthcare disciplines and
managers should be initiated to establish shared moral understanding of the
standards of care in hospitals.
PMID- 17042821
TI - What makes a good midwife? An integrative review of methodologically-diverse
research.
AB - AIM: This paper reports an integrative review aimed at answering the question:
'What makes a good midwife?' BACKGROUND: A research-based definition of a good
midwife which can be used as an operational definition in research and as a basis
for curriculum development could not be found. Research in nursing has identified
that patients and nurses may give different responses when asked about the most
important aspects of nurses' contribution to care. It is also possible that views
of how to define a good midwife might differ. METHODS: A four-stage systematic
review process was used, consisting of protocol development, carrying out the
search, appraisal/analysis of the papers retrieved, and synthesis of the
information. The initial search covered the period from 1993 and used the
keywords 'midwi*', 'nurse-midwi*' and 'good'. This was later extended to include
the terms 'exemplary', 'excellent' and 'superb' as synonyms of 'good', and 'bad'
as its antonym. The integrative review was descriptive and focussed on extracting
from the papers the findings that contributed to answering the research question.
FINDINGS: Thirty-three research-based papers were included in the review, and
these had used a range of approaches and methods. Eight key concepts were derived
from the data: attributes of a midwife, education, research, what a midwife does,
care organization, other professionals, partners and an international
perspective. CONCLUSION: Having good communication skills made the greatest
contribution to being 'a good midwife', while being compassionate, kind,
supportive (affective domain), knowledgeable (cognitive domain) and skilful
(psychomotor domain) also made major contributions. Being involved in education
and research were necessary requirements, and midwives' abilities to treat women
as individuals, adopt a caring approach, and 'be there' for women were essential.
A good midwife can compensate for poor management systems, but women should be
able to choose who provides their care, and partners should be involved in this
care.
PMID- 17042822
TI - The art of public health nursing: using confession techne in the sexual health
domain.
AB - AIM: This paper explores the sexual health interview from a critical perspective,
and to demonstrate how the confession ritual involved in this interview is
implicated in the construction of subjectivities (meaning identities) as well as
in fostering self-surveillance (self-regulation). BACKGROUND: The concept of
public health depends primarily on several surveillance tools that monitor both
the incidence and prevalence rates of certain diseases. Within the subgroup of
infectious diseases, sexually transmitted infections comprise a group that is
closely monitored. As a result, surveillance techniques, including policing
sexual practices, are part of the public health worker's mandate. METHOD: Using a
Foucauldian perspective, we demonstrate that confession is a political technology
in the sexual health domain. FINDINGS: As one group of frontline workers in the
field of sexual health, nurses are responsible for data collection through
methods such as interviewing clients. Nurses play an integral role in the sexual
health experience of clients as well as in the construction of the client's
subjectivity. We strongly believe that a Foucauldian perspective could be useful
in explaining certain current client behavioural trends (for example, an
avoidance by at-risk groups of interactions with nurses in sexual health clinics)
being observed in sexual health clinics across the Western hemisphere.
CONCLUSION: Clinicians need to be aware of the confessional nature of their
questions and provide requested services rather than impose services that they
determine to be important and relevant. By appreciating that the sexual health
interview is an invasive and embarrassing sexual confession, healthcare providers
and policy-makers may be better able to design and implement more user-oriented,
population-sensitive sexual health services.
PMID- 17042823
TI - Work-related fatigue and recovery: the contribution of age, domestic
responsibilities and shiftwork.
AB - AIM: This paper reports a study of the relationship between age, domestic
responsibilities (being partnered and having dependents), recovery from shiftwork
related fatigue and the evolution of maladaptive health outcomes among full-time
working female nurses. BACKGROUND: Several studies have suggested that full-time
working women with family responsibilities are at greater risk of developing work
related fatigue problems than single women without these responsibilities.
METHOD: A questionnaire was distributed in 2004 to 2400 nurses at two hospitals
in Australia, and 1280 responses were obtained (response rate 54%). The data from
a purposive sample of 846 full-time working nurses are reported here. FINDINGS:
Domestic responsibilities were not related to differences in fatigue and
recovery. Our results suggested that for full-time shiftworking nurses, being
part of a family structure, may actually be protective against the development of
maladaptive fatigue. The most important factor determining maladaptive fatigue
outcome was shift pattern worked, particularly rotation including night duty. The
effect of age was equivocal. The youngest age group reported the highest fatigue
and poorest recovery compared to the oldest group, who reported the best
characteristics. However, this latter group may represent a particularly well
adapted 'survivor cohort'. The relationship between age and fatigue was partly
confounded by older, experienced, nurses with greater job responsibilities,
working fewer multiple shifts including night duty. In general, increasing age
was not associated with poorer recovery or higher maladaptive fatigue.
CONCLUSIONS: Unpredictable internal shift rotations, including night duty, which
are traditional and typical in nursing, are inimical to maintaining nurses'
health. More creative approaches to rostering for nurses working multiple shifts
are a necessary step towards reducing wastage from the profession due to chronic
work-related fatigue. Younger nurses in particular, may need more support than is
currently recognized if they are to be retained within the profession.
PMID- 17042826
TI - Rational approaches to the neurobiologic study of youth at risk for bipolar
disorder and suicide.
AB - OBJECTIVES: The aims of this paper are to provide an overview of neuroimaging
findings specific to bipolar disorder and suicide, and to consider rational
approaches to the design of future in vivo studies in youth at risk. METHODS:
Neuroimaging and related neurobiological literature pertaining to bipolar
disorder and suicide in adult and pediatric samples was reviewed in a non
quantitative manner. RESULTS: Specific structural and functional brain findings
in bipolar disorder are described, where possible in the context of relevant
current neurobiological theories of etiology. Diagnostic and prognostic
implications are discussed. CONCLUSIONS: The simultaneous use of complementary
neurobiological approaches may be a powerful way of identifying and validating
factors reliably associated with bipolar disorder and suicide. A profile of
neurobiological markers with which to screen for bipolar disorder and suicide
risk may provide for earlier and more accurate diagnosis, perhaps even in the pre
or subsyndromal stages in high-risk youth.
PMID- 17042828
TI - Correlates of suicide attempt history in bipolar disorder: a stress-diathesis
perspective.
AB - OBJECTIVES: Distinguishing clinical characteristics of bipolar patients who have
made a suicide attempt may help to identify at-risk individuals. We sought to
identify such factors and to consider them within a stress-diathesis model of
suicidal behavior. METHODS: Patients with bipolar disorder (N = 96) were compared
with respect to the presence or absence at baseline evaluation of a history of
suicide attempt. We used multiple logistic regression analysis to assess the
unique associations of independent variables to history of a past suicide
attempt. RESULTS: The regression analysis showed that a history of suicide
attempt in bipolar disorder was associated with greater recent suicidal ideation,
more psychiatric hospitalizations, lifetime aggressive traits and an earlier age
at onset of a first mood episode. CONCLUSIONS: Aggressive traits and early
treatment of mood disorders, especially major depressive episodes, are potential
targets for suicide prevention in bipolar disorder.
PMID- 17042827
TI - A prospective study of the association of cerebrospinal fluid monoamine
metabolite levels with lethality of suicide attempts in patients with bipolar
disorder.
AB - OBJECTIVES: Bipolar disorder is a severe illness that is associated with suicidal
behavior. A biological predictor of highly lethal suicide attempts in patients
with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid
(CSF) monoamine metabolite levels are related to lethality of suicide attempts in
bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid
(5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)
levels and maximum lethality of suicide attempts at baseline and during a 2-year
follow up. METHODS: Twenty-seven bipolar depressed patients participated in the
study. Demographic and clinical parameters were examined and recorded. Lumbar
punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high
performance liquid chromatography with electrochemical detection. Following
discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each
follow-up interview included an in-depth assessment of suicidal behavior during
the intervening time period. RESULTS: Six subjects made suicide attempts during
the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up
period had higher aggression and hostility scale scores compared to bipolar
subjects who did not make a suicide attempt during the follow-up period. CSF 5
HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality
of suicide attempts during the 2-year follow-up period. CONCLUSIONS: Our finding
is the first observation that CSF monoamine metabolite levels may be predictors
of lethality of suicide attempts in patients with bipolar disorder. Further
studies are necessary to answer the question whether CSF monoamine metabolite
levels are clinically useful biochemical predictors of highly lethal suicide
attempts or completed suicides.
PMID- 17042829
TI - A comparison of the medical lethality of suicide attempts in bipolar and major
depressive disorders.
AB - OBJECTIVES: Among mood disorders, bipolar disorder (BPD) is often noted to
involve the highest rates of suicide attempts and possibly of completion. This
study sought to determine whether suicide attempters with BPD exhibit suicide
attempts with higher lethality than attempters with major depressive disorder
(MDD) and to explore differences in clinical features associated with suicidal
acts. METHODS: Mood disordered suicide attempters were interviewed about Axis I
and II diagnoses, lifetime history of suicide attempts, suicidal intent, suicidal
ideation, the medical lethality of their most severe suicide attempt, severity of
depression, hopelessness, lifetime aggression, and impulsivity. RESULTS: The
maximum lethality of suicidal acts tended to be higher among BPD attempters
compared with those with MDD. However, there were no differences in the number of
suicide attempts, intent to die or suicidal ideation. Suicide attempters with BPD
reported higher levels of aggression and impulsivity but less hopelessness
compared with MDD attempters. These differences could not be explained by Cluster
B personality disorder comorbidity. Of note, within the BPD group, but not the
MDD group, males reported suicidal acts with higher lethality. Multivariate
analyses suggested that risk for more lethal suicide attempts is associated with
BPD and male sex and that bipolar males appear to be especially vulnerable to
these behaviors. CONCLUSIONS: Males with BPD make more lethal suicide attempts
than females with BPD, an effect not observed among the MDD sample. Our findings
suggest that higher rates of suicidal behavior in BPD may be due to a specific
effect of BPD on males, leading to more dangerous suicidal behaviors. This
effect, together with the larger proportion of males in the BPD group compared
with the MDD group may lead to higher rates of reported attempted and completed
suicide.
PMID- 17042830
TI - Prospective predictors of suicide and suicide attempts in 1,556 patients with
bipolar disorders followed for up to 2 years.
AB - OBJECTIVES: Bipolar disorders are associated with high rates of suicide attempts
(SAs) and completions. Several factors have been reported to be associated with
suicide in persons with bipolar disorder, but most studies to date have been
retrospective and have not utilized multivariate statistics to account for the
redundant prediction among variables submitted for analysis. METHODS: This study
examined the association between baseline clinical and demographic variables and
subsequent SAs and completions through 2 years of follow-up of participants in
the Systematic Treatment Enhancement Program for Bipolar Disorder using a pattern
mixture model. RESULTS: Of the sample with complete data (n = 1,556), 57 patients
(3.66%) experienced an SA or completion (CS). Several variables predicted
suicidality (SA + CS) in this data set when considered alone, but after
controlling for redundant prediction from other baseline characteristics, only
history of suicide [odds ratio (OR) = 4.52, p < 0.0001] and percent days
depressed in the past year (OR = 1.16, p = 0.036) were significantly associated
with SAs and completions. A secondary analysis included a greater number of
variables but a smaller sample size (n = 1,014). In the secondary analyses, only
prior SAs predicted prospective suicidality (OR = 3.87, p = 0.0029). CONCLUSIONS:
These results indicate that patients with bipolar disorder who present with a
history of SAs are over four times as likely to have a subsequent SA or
completion. Further studies are needed to evaluate and prevent future attempts in
this high-risk cohort.
PMID- 17042831
TI - Prospective study of risk factors for attempted suicide among patients with
bipolar disorder.
AB - OBJECTIVE: There are few prospective studies on risk factors for attempted
suicide among representative samples of psychiatric patients with bipolar I and
II disorders. We conducted a prospective study to investigate risk for suicide
attempts among a secondary-level sample of psychiatric in- and outpatients with
bipolar disorder (BD). METHODS: In the Jorvi Bipolar Study (JoBS), 1,630
psychiatric in- and outpatients from three Finnish cities were screened for BDs
with the Mood Disorder Questionnaire (MDQ). Using the Structured Clinical
Interview for DSM-IV Disorders (SCID)-I and -II, 191 patients were diagnosed with
BDs (90 bipolar I and 101 bipolar II). Information on suicide attempts during the
follow-up was obtained for 176 patients (92%) at the 6-month follow-up and for
160 patients (84%) at the 18-month follow-up. RESULTS: During the 18-month follow
up 20% of patients (35/176) attempted suicide. In a Cox regression model,
baseline previous suicide attempts (OR 3.8, 95% CI 1.7-8.8; p = 0.001),
hopelessness (OR 1.2, 95% CI 1.1-1.3; p < 0.001), depressive phase at index
episode (OR 2.4, 95% CI 1.1-5.3; p = 0.03) and younger age at intake (OR 0.94,
95% CI 0.91-0.97; p < 0.001) were independent risk factors for suicide attempts
during follow-up, whereas factors such as bipolar I or II, or comorbidity did not
reach statistical significance. CONCLUSIONS: During a medium-term follow-up, as
many as one-fifth of random psychiatric patients with BD attempted suicide, which
highlights the public health importance of suicidal behavior in BD. Previous
suicide attempts, hopelessness and depressive phase were the key indicators of
risk.
PMID- 17042832
TI - Clinical predictors of suicidal acts after major depression in bipolar disorder:
a prospective study.
AB - OBJECTIVE: This study determined the clinical predictors of suicidal behavior
during a 2-year follow-up of patients with bipolar disorder presenting with a
major depressive episode (MDE). METHOD: Sixty four patients with DSM-III-R
bipolar disorder were assessed at presentation for treatment of an MDE.
Correlates of past suicidal behavior were determined by comparing patients with
and without a history of suicide attempts using a t-test, Wilcoxon test or chi
squared test of independence on individual explanatory variables. Putative
predictors of attempts during the follow-up period were tested separately using
Cox proportional hazards regression analysis. RESULTS: Twelve of 64 patients had
at least one suicide attempt in the follow-up period, five of them attempted in
the first 2 months and seven around or shortly after the 1-year follow-up visit.
All attempters had a history of past suicide attempts. Most predictors of future
suicidal behavior were correlates of past suicidal behavior. Family history of
suicide acts and comorbid borderline personality disorder predicted early
attempts, while younger age, high hostility scores, number of past attempts,
subjective pessimism as reflected in depression and suicidal ideation, and few
reported reasons for living predicted suicidal acts during the whole period.
CONCLUSION: In this data set of bipolar patients we noted an intriguing picture
of two clusters of suicide attempts. Hostility was the strongest risk factor.
These findings may have implications in both the identification of at-risk
patients and the timing of clinical interventions including aggressive
pharmacotherapeutic prophylaxis to prevent relapse or recurrence of depressive
symptomatology.
PMID- 17042833
TI - Antidepressants and suicidal behavior in bipolar disorder.
AB - Patients with bipolar disorder are at very high risk for suicidal ideation, non
fatal suicidal behaviors and suicide and are frequently treated with
antidepressants. However, no prospective, randomized, controlled study
specifically evaluating an antidepressant on suicidality in bipolar disorder has
yet been completed. Indeed, antidepressants have not yet been shown to reduce
suicide attempts or suicide in depressive disorders and may increase suicidal
behavior in pediatric, and possibly adult, major depressive disorder. Available
data on the effects of antidepressants on suicidality in bipolar disorder are
mixed. Considerable research indicates that mixed states are associated with
suicidality and that antidepressants, especially when administered as
monotherapy, are associated with both suicidality and manic conversion. In
contrast, growing research suggests that antidepressants administered in
combination with mood stabilizers may reduce depressive symptoms in patients with
bipolar depression. Further, the only prospective, long-term study evaluating
antidepressant treatment and mortality in bipolar disorder, although open-label,
found antidepressants and/or antipsychotics in combination with lithium, but not
lithium alone, reduced suicide in bipolar and unipolar patients (Angst F, et al.
J Affect Disord 2002: 68: 167-181). We conclude that antidepressants may induce
suicidality in a subset of persons with depressive (and probably anxious)
presentations; that this induction may represent a form of manic conversion, and
hence a bipolar phenotype, and that lithium's therapeutic properties may include
the ability to prevent antidepressant-induced suicidality.
PMID- 17042834
TI - Suicidal risk in bipolar I disorder patients and adherence to long-term lithium
treatment.
AB - OBJECTIVES: Among the well-established treatments for bipolar disorder (BPD),
lithium continues to offer an unusually broad spectrum of benefits that may
include reduction of suicidal risk. METHODS: We examined the association of
suicidal acts with adherence to long-term lithium maintenance treatment and other
potential risk factors in 72 BP I patients followed prospectively for up to 10
years at a Mood Disorders Research Center in Spain. RESULTS: The observed rates
of suicide were 0.143, and of attempts, 2.01%/year, with a 5.2-fold (95% CI: 1.5
18.6) greater risk among patients consistently rated poorly versus highly
adherent to lithium prophylaxis (11.4/2.2 acts/100 person-years). Treatment non
adherence was associated with substance abuse, being unmarried, being male, and
having more hypomanic-manic illness and hospitalizations. Suicidal risk was
higher with prior attempts, more depression and hospitalization, familial mood
disorders, and being single and younger, as well as treatment non-adherence, but
with neither sex nor substance abuse. In multivariate analysis, suicidal risk was
associated with previous suicidality > poor treatment adherence > more depressive
episodes > younger age. CONCLUSIONS: The findings support growing evidence of
lower risk of suicidal acts during closely monitored and highly adherent, long
term treatment with lithium and indicate that treatment adherence is a
potentially modifiable factor contributing to antisuicidal benefits.
PMID- 17042835
TI - Decreased risk of suicides and attempts during long-term lithium treatment: a
meta-analytic review.
AB - OBJECTIVES: To update and extend comparisons of rates of suicides and suicide
attempts among patients with major affective disorders with versus without long
term lithium treatment. METHODS: Broad searching yielded 45 studies providing
rates of suicidal acts during lithium treatment, including 34 also providing
rates without lithium treatment. We scored study quality, tested between-study
variance, and examined suicidal rates on versus off lithium by meta-analytic
methods to determine risk ratios (RRs) and 95% confidence intervals (CI).
RESULTS: In 31 studies suitable for meta-analysis, involving a total of 85,229
person-years of risk-exposure, the overall risk of suicides and attempts was five
times less among lithium-treated subjects than among those not treated with
lithium (RR = 4.91, 95% CI 3.82-6.31, p < 0.0001). Similar effects were found
with other meta-analytic methods, as well as for completed versus attempted
suicide, and for bipolar versus major mood disorder patients. Studies with higher
quality ratings, including randomized, controlled trials, involved shorter
exposures with somewhat lesser lithium superiority. Omitting one very large study
or those involving lithium-discontinuation had little effect on the results. The
incidence-ratio of attempts-to-suicides increased 2.5 times with lithium
treatment, indicating reduced lethality of suicidal acts. There was no indication
of bias toward reporting positive findings, nor were outcomes significantly
influenced by publication-year or study size. CONCLUSIONS: Risks of completed and
attempted suicide were consistently lower, by approximately 80%, during treatment
of bipolar and other major affective disorder patients with lithium for an
average of 18 months. These benefits were sustained in randomized as well as open
clinical trials.
PMID- 17042836
TI - Family-focused treatment of the suicidal bipolar patient.
AB - OBJECTIVES: Bipolar patients are at high risk for suicidal ideation and attempts.
Suicidal behavior is correlated with poor family communication and/or high levels
of intrafamilial conflict, particularly among adolescent bipolar patients. This
article describes the application of family-focused therapy (FFT) as an adjunct
to pharmacotherapy in the management of suicidal ideation and behavior among
bipolar patients. METHODS: We describe the empirical basis of FFT in studies of
adult and adolescent patients. We then describe the manner by which the three
modules of FFT - psychoeducation, communication skills training and problem
solving - are adapted to address the clinical issues presented by suicidal
bipolar adults or adolescents and their families. RESULTS: Key objectives of the
treatment are to help the family recognize that suicidal behavior is a part of
the pathophysiology of bipolar disorder but that it is also to some extent under
environmental control. Thus, the family is in a unique position to develop and
help assure the success of a suicide prevention contract. A case study of an
adolescent with suicidal behavior is presented. CONCLUSIONS: Future research
should include a focus on: (i) cross-cultural issues in suicide and bipolar
disorder; and (ii) the adaptation of interventions shown to be effective in
reducing suicidal behaviors in non-bipolar populations.
PMID- 17042837
TI - What is vital to measure?
PMID- 17042838
TI - The cat in the kitchen: problems with the Pippa technique.
PMID- 17042839
TI - A randomised controlled trial of the effect of continuous electronic
physiological monitoring on the adverse event rate in high risk medical and
surgical patients.
AB - We conducted a randomised controlled trial of mandated five-channel physiological
monitoring vs standard care, in acute medical and surgical wards in a single UK
teaching hospital. In all, 402 high-risk medical and surgical patients were
studied. The primary outcome was the proportion of patients experiencing one or
more major adverse events, including urgent staff calls, changes to higher care
levels, cardiac arrests or death, in 96 h following randomisation. Secondary
outcomes were the proportion of patients requiring acute treatment changes, and
the 30-day and hospital mortality. In the 96 h following randomisation, 113 (56%)
patients in the monitored arm and 116 (58%) in the control arm (OR 0.94, 95% CI
0.63-1.40, p = 0.76) had a major event. An acute change in treatment was
necessary in 107 (53%) monitored patients and 101 (50%) control patients (OR
0.55, 95% CI 0.87-1.29). Thirty-four (17%) monitored patients and 35 (17%)
control patients died within 30 days. Thirteen patients in the control group
received full five-channel monitoring at the request of the ward staff. We
conclude that mandated electronic vital signs monitoring in high risk medical and
surgical patients has no effect on adverse events or mortality.
PMID- 17042840
TI - Effect of propofol on seizure-like phenomena and electroencephalographic activity
in children with epilepsy vs children with learning difficulties.
AB - There is an ongoing debate as to whether propofol exhibits pro- or anticonvulsant
effects, and whether it should be used in patients with epilepsy. We
prospectively assessed the occurrence of seizure-like phenomena and the effects
of intravenous propofol on the electroencephalogram (EEG) in 25 children with
epilepsy (mean (SD) age: 101 (49) months) and 25 children with learning
difficulties (mean (SD) age: 52 (40) months) undergoing elective sedation for MRI
studies of the brain. No child demonstrated seizure-like phenomena of epileptic
origin during and after propofol sedation. Immediately after stopping propofol,
characteristic EEG changes in the epilepsy group consisted of increased beta wave
activity (23/25 children), and suppression of pre-existing theta rhythms (11/16
children). In addition, 16 of 18 children with epilepsy and documented EEG
seizure activity demonstrated suppression of spike-wave patterns after propofol
sedation. In all 25 children with learning difficulties an increase in beta wave
activity was seen. Suppression of theta rhythms occurred in 11 of 12 children at
the end of the MRI study. In no child of either group was a primary occurrence or
an increase in spike-wave patterns seen following propofol administration. The
occurrence of beta wave activity (children with learning difficulties and
epilepsy group) and suppression of spike-wave patterns (epilepsy group) were
transient, and disappeared after 4 h. This study demonstrates characteristic,
time-dependent EEG patterns induced by propofol in children with epilepsy and
learning difficulties. Our data support the concept of propofol being a sedative
hypnotic agent with anticonvulsant properties as shown by depression of spike
wave patterns in children with epilepsy and by the absence of seizure-like
phenomena of epileptic origin.
PMID- 17042841
TI - A comparison of an anterior jaw lift manoeuvre with the Berman airway for
assisting fibreoptic orotracheal intubation.
AB - This study compared the efficacy of an anterior jaw lift manoeuvre with that of
the Berman airway in clearing the upper airway during oral fibreoptic tracheal
intubation in anaesthetised, paralysed patients. Fifty patients were randomly
assigned to undergo fibreoptic-assisted intubation with one method, followed by
crossover to the alternative method. The time taken to view the vocal cords was
the primary endpoint, and we also noted the rate of failure to view the cords,
i.e. cords not seen after 120 s of endoscopy. Anterior jaw lift yielded
significantly shorter times to view the vocal cords (median [interquartile range;
range]: 22 [17-46; 7-120] s vs 40 [29-67; 21-120] s, p = 0.001) and a higher
success rate (49/50 vs 42/50, p = 0.014). We conclude that the anterior jaw lift
is more effective than the Berman device for achieving airway clearance in this
setting.
PMID- 17042842
TI - A comparison of cyclizine and granisetron alone and in combination for the
prevention of postoperative nausea and vomiting.
AB - We conducted a randomised double-blinded study of 960 women undergoing day-case
surgery to determine whether combination anti-emetic therapy of granisetron and
cyclizine was more effective at decreasing the incidence of postoperative nausea
and vomiting than these agents used alone. The women were randomly allocated to
three groups to receive intravenous granisetron 1 mg, cyclizine 50 mg or both
before induction of general anaesthesia. The incidence of postoperative nausea
and vomiting was 77/322 (24%) in the granisetron group, 73/316 (23%) in the
cyclizine group and 53/322 (17%) in those women given both drugs (p = 0.04).
There was no difference in the requirement for rescue anti-emetic drugs. There
were no differences in the anaesthetic techniques used in the three groups. We
conclude that the risk of postoperative nausea and vomiting is less with
cyclizine and granisetron given together than with either given alone.
PMID- 17042843
TI - The role of magnesium as an adjuvant during general anaesthesia.
AB - Magnesium sulphate is used extensively in the treatment of eclampsia, and is also
used to treat refractory arrhythmias, asthma, myocardial ischaemia and acute
respiratory failure. We studied the interaction between magnesium sulphate and
the anaesthetic agents propofol, rocuronium bromide and fentanyl citrate. This
randomised, double blind study was conducted in 50 patients. The magnesium group
A (n = 25) received 30 mg x kg(-1) magnesium sulphate before induction of
anaesthesia and 10 mg x kg(-1) continuously intra-operatively until the end of
surgery. Group B (n = 25) received the same volume of isotonic saline. Propofol,
rocuronium and fentanyl infusions were started and the patients lungs' were
ventilated with 33% oxygen in nitrous oxide. Anaesthetic depth was maintained at
a bispectral index value of between 40 and 60. Muscle relaxation was maintained
at a train-of-four count of 1 throughout surgery using neuromuscular monitoring.
The fentanyl infusion was titrated to haemodynamic variables: heart rate and
blood pressure. We concluded that magnesium sulphate has anaesthetic, analgesic
and muscle relaxation effects and significantly reduces the drug requirements of
propofol, rocuronium and fentanyl during anaesthesia.
PMID- 17042844
TI - A comparison of nerve stimulator guided paravertebral block and ilio-inguinal
nerve block for analgesia after inguinal herniorrhaphy in children.
AB - The aim of this study was to compare the efficacy of nerve stimulator guided
paravertebral block with ilio-inguinal nerve block in children undergoing
inguinal herniorrhaphy. Eighty children were randomly allocated to receive either
paravertebral block or ilio-inguinal nerve block. Each block was evaluated in
terms of intra-operative haemodynamic stability, postoperative pain scores at
rest, on movement and during activity, requirement for supplemental analgesia and
parental satisfaction. Haemodynamic stability was maintained significantly better
during sac traction in the paravertebral block group (p < 0.005). Pain scores and
analgesic consumption were significantly lower in the paravertebral block group
during the postoperative follow-up period (p < 0.05). Parental satisfaction
(93%vs 69%) and surgeon satisfaction (93%vs 64%) were significantly higher in the
paravertebral block group (p < 0.05). Paravertebral blockade improved and
prolonged postoperative analgesia, and was associated with greater parental and
surgeon satisfaction when compared to ilio-inguinal nerve block.
PMID- 17042845
TI - Thomas the Tank Engine and Friends improve the understanding of oxygen delivery
and the pathophysiology of hypoxaemia.
AB - Understanding basic pathophysiological principles underpins the practice of many
healthcare workers, particularly in a critical care setting. Undergraduate
curricula have the potential to separate physiology teaching from clinical
contexts, making understanding difficult. We therefore assessed the use of
analogous imagery as an aid to understanding. Two groups of first year
physiotherapy students were randomly assigned to receive either a control lecture
(oxygen delivery and hypoxaemia) or a study lecture (control lecture plus images
of a train set delivering rocks: an analogy to oxygen delivery.) Qualitative
assessment of the lectures showed a significant (p < 0.001) improvement in
understanding by the study group, and increased the proportion of students that
found the lecture 'interesting and stimulating' (p = 0.01). Quantitative
assessment demonstrated a significant increase in the multiple choice
questionnaire marks of the study group (p = 0.03). In conclusion, analogous
imagery can significantly increase the understanding of this physiological
concept.
PMID- 17042846
TI - Brain stem death testing after thiopental use:A survey of UK neuro critical care
practice.
AB - A postal survey was conducted to determine how thiopental is used in UK
neurosurgery critical care units. Thirty units were contacted and 26 replied.
Thiopental is used in 23 units. The majority (60%) of these units govern the use
of thiopental with protocols or guidelines and 74% use cerebral monitoring to
guide dosage. When patients have had thiopental, 20 units delay brain stem
testing, two will not perform tests and one unit incorporates cerebral
angiography into their protocol. Twelve units use serum thiopental assays in
their brain stem testing procedures, but there is wide variation in the
interpretation of the results. We found inconsistency and confusion surrounding
brain stem testing in this patient group, raising the possibility of misdiagnosis
of brain stem death.
PMID- 17042847
TI - An evaluation of protocolised weaning on the duration of mechanical ventilation.
AB - Using a before and after study design, we compared protocolised weaning from
mechanical ventilation with usual non-protocolised practice in intensive care.
Outcomes (duration of mechanical ventilation, duration of intubation, intensive
care stay) and complications (re-intubations, tracheostomy, mortality) were
compared between baseline (Phase I) and following implementation of protocolised
weaning (Phase II). Over the same period, we collected data in a second
(reference) unit to monitor practice changes over time. In the intervention unit,
outcomes were longer in Phase II compared with Phase I (all p < 0.005). When
adjusted for admission APACHE II score and diagnostic category, only intensive
care stay remained significantly longer (p = 0.002). There were significantly
more tracheostomies in Phase II (p = 0.004). The reference unit demonstrated no
statistically significant differences in study outcomes or complications between
Phases. Protocolised weaning did not reduce the duration of mechanical
ventilation and was not associated with an increased rate of re-intubation or
intensive care unit mortality.
PMID- 17042848
TI - An observational study of changes to long-term medication after admission to an
intensive care unit.
AB - Many patients admitted to intensive care units consume long-term medication. New
drugs may be commenced during intensive care intended for the short term or
longer. Patients are often cared for by several teams during hospital admission
and long-term medication may inadvertently be permanently discontinued. Following
admission, new therapies relevant only in the short term could be continued
beyond intensive care and hospital discharge. We conducted a retrospective
analysis of drug prescription by examining patients' notes and charts before,
during and after intensive care admission. Of 197 drugs prescribed up to
intensive care admission to 59 patients, 112 (57%) were stopped. Ninety-nine of
these were not reintroduced by intensive care discharge and 34 were not
reintroduced by hospital discharge. Of 154 drugs commenced during intensive care,
96 (62%) had no listed reason for their introduction. Twenty-eight were continued
beyond hospital discharge, some without apparent ongoing indication. Reliable
mechanisms to prevent prescription errors are required.
PMID- 17042849
TI - A comparison of tracheal intubation using the Airtraq or the Macintosh
laryngoscope in routine airway management: A randomised, controlled clinical
trial.
AB - The Airtraq laryngoscope is a novel single use tracheal intubation device. We
compared the Airtraq with the Macintosh laryngoscope in patients deemed at low
risk for difficult intubation in a randomised, controlled clinical trial. Sixty
consenting patients presenting for surgery requiring tracheal intubation were
randomly allocated to undergo intubation using a Macintosh (n = 30) or Airtraq (n
= 30) laryngoscope. All patients were intubated by one of four anaesthetists
experienced in the use of both laryngoscopes. No significant differences in
demographic or airway variables were observed between the groups. All but one
patient, in the Macintosh group, was successfully intubated on the first attempt.
There was no difference between groups in the duration of intubation attempts. In
comparison to the Macintosh laryngoscope, the Airtraq resulted in modest
improvements in the intubation difficulty score, and in ease of use. Tracheal
intubation with the Airtraq resulted in less alterations in heart rate. These
findings demonstrate the utility of the Airtraq laryngoscope for tracheal
intubation in low risk patients.
PMID- 17042850
TI - Comparison of forced-air warming and electric heating pad for maintenance of body
temperature during total knee replacement.
AB - We conducted a randomised controlled trial to compare the efficacy of forced-air
warming (Bair Hugger(trade mark), Augustine Medical model 500/OR, Prairie, MN)
with that of an electric heating pad (Operatherm 202, KanMed, Sweden) for
maintenance of intra-operative body temperature in 60 patients undergoing total
knee replacement under combined spinal-epidural anaesthesia. Intra-operative
tympanic and rectal temperatures and verbal analogue score for thermal comfort
were recorded. There were no differences in any measurements between the two
groups, with mean (SD) final rectal temperatures of 36.8 (0.4) degrees C with
forced-air warming and 36.9 (0.4) degrees C with the electric pad. The heating
pad is as effective as forced-air warming for maintenance of intra-operative body
temperature.
PMID- 17042851
TI - Total spinal anaesthesia after an attempted brachial plexus block using the
posterior approach.
AB - A 66-year-old patient scheduled for elective shoulder surgery underwent a
brachial plexus block using the posterior approach. Shortly after injection of
the local anaesthetic, he rapidly became unresponsive and apnoeic. We identify
the possible reasons for this occurrence and discuss the place of the posterior
approach in brachial plexus anaesthesia.
PMID- 17042852
TI - Acquired C1 esterase inhibitor deficiency: An atypical first presentation intra
operatively.
AB - We report a case of airway difficulties encountered as a result of blistering,
oedema and bleeding from the oropharyngeal mucosa of an 85-year-old female
undergoing an elective excision of a submandibular neck lump. This led to a delay
in extubation by several hours. The patient was subsequently found to have an
acquired form of C1 esterase inhibitor deficiency considered to be consequent of
haematological malignancy.
PMID- 17042853
TI - The management of severe emergence agitation using droperidol.
AB - Emergence agitation can occur following recovery from general anaesthesia. The
patient may exhibit aggressive behaviour, disorientation, agitation and
restlessness. Untreated, this complication may result in significant morbidity.
We report two cases where droperidol was successfully used in the management of
severe emergence agitation. In the first case, droperidol was administered to
prevent the occurrence of postoperative agitation in a patient known to suffer
from this condition following previous general anaesthetics. In the second case,
droperidol was used to treat emergence agitation in a morbidly obese patient with
a difficult airway who was aggressive and difficult to restrain. Both of these
patients remained calm and co-operative, with stable cardio-respiratory
parameters, following the administration of droperidol and showed no further
signs of agitation. We suggest that droperidol is an effective medication that
may be used to prevent and treat severe emergence agitation due to its rapid
sedative effect and minimal cardio-respiratory depression.
PMID- 17042854
TI - Lipid emulsion for local anaesthetic toxicity.
PMID- 17042856
TI - Local anaesthetic toxicity: prevention or cure?
PMID- 17042858
TI - The difference between the use (or not) of 'resuscitative measures' and 'Do Not
Attempt Resuscitation' requests.
PMID- 17042859
TI - Lipid emulsion for local anaesthetic toxicity.
PMID- 17042860
TI - Decision making and decision analysis.
PMID- 17042861
TI - Emergency Caesarean section--best practice.
PMID- 17042864
TI - The effects of general anaesthesia on children.
PMID- 17042865
TI - Sub-mental vs. retromolar intubation.
PMID- 17042866
TI - The Triservice Anaesthetic Apparatus--an alternative configuration.
PMID- 17042867
TI - Burn following use of the Suntouch warmer.
PMID- 17042868
TI - Variability of Guedel-type airways.
PMID- 17042870
TI - Ultrasound-guided ilio-inguinal and rectus sheath nerve blocks.
PMID- 17042871
TI - Awareness, dreaming or steroid-induced psychosis?
PMID- 17042872
TI - Nasogastric tube insertion--another technique.
PMID- 17042873
TI - Povidone-iodine antisepsis before ophthalmic surgery.
PMID- 17042874
TI - Phantom capnograph.
PMID- 17042878
TI - Patterns of oscillatory behavior in different human systems: a special reference
to psychiatry and techniques to quantify such patterns.
PMID- 17042880
TI - Approximate entropy of self-reported mood prior to episodes in bipolar disorder.
AB - BACKGROUND: Approximate entropy (ApEn) measures regularity in time series data,
while traditional linear statistics measure variability. Using self-reported mood
data from patients with bipolar disorder, this preliminary study addressed
whether ApEn could distinguish (i) the 60 days prior to the start of a manic or
depressed episode from the 60 days prior to a month of euthymia, and (ii) the 60
days prior to a manic episode from the 60 days prior to a depressed episode.
METHODS: Self-reported mood data from 49 outpatients with bipolar disorder
receiving standard treatment were analysed. The data contained 27 episodes (12
manic and 15 depressed), and 43 periods of 1 month of euthymia. For the 60 days
prior to episode or euthymia, the ApEn, linear statistics and the correlation
between linear and non-linear measures were calculated. RESULTS: ApEn was
significantly greater in the 60 days prior to a manic or depressive episode than
the 60 days prior to a month of euthymia. The onset of an episode was associated
with greater irregularity in mood. Variability was also significantly larger and
correlated with ApEn. ApEn was significantly greater in the 60 days prior to a
manic episode than in the 60 days prior to a depressed episode, whereas measures
of variability were not significantly different. Mood in the 60 days prior to
mania was more irregular than prior to depression. CONCLUSIONS: Non-linear
measures may complement traditional linear measures in the analysis of
longitudinal data in bipolar disorder. A larger study is indicated.
PMID- 17042881
TI - Approximate entropy as a measure of irregularity for psychiatric serial metrics.
AB - OBJECTIVES: The quantification of subtle patterns in sequential data, and their
changes, has considerable potential utility throughout psychiatry, including the
analyses of mood ratings, heart rate, respiratory, and electroencephalographic
recordings. METHODS: Approximate entropy (ApEn), a relatively recently developed
statistic quantifying serial irregularity, has been applied in numerous studies
throughout mathematics and other fields of study, especially biology. RESULTS: We
discussed applications of ApEn, both extant and potential, of most relevance to
psychiatrists. We provided a mechanistic interpretation of lowered ApEn values,
and discusses the relationship between ApEn and other (both classical and
complexity) measures of serial dynamics. We also briefly discussed cross-ApEn, a
thematically similar quantification of two-variable asynchrony that can aid in
uncovering subtle disruptions in complicated network dynamics. CONCLUSIONS: ApEn
and cross-ApEn have significant potential to consequentially enhance present
statistical methodologies of analysis of psychiatric data, in both clinical and
in research settings.
PMID- 17042882
TI - Linear and nonlinear methods for analyses of cardiovascular variability in
bipolar disorders.
AB - OBJECTIVES: Heart rate variability (HRV), blood pressure variability (BPV), and
the assessment of baroreflex sensitivity are widely accepted methods for
analyzing and characterizing cardiovascular regulation and for an enhanced risk
evaluation in different diseases. As a result of the complexity of the
investigated regulatory systems, univariate analyses do not often provide a
convenient description of pathological changes in the cardiovascular regulation.
Therefore, the application of a multivariate approach is preferable. METHODS: We
present principal methods of time-domain, frequency-domain, and nonlinear
analyses of HRV, BPV as well as methods for coupling and interaction analyses.
RESULTS: Changes in autonomic nervous system (ANS) tone are known to accompany
various mental disorders. Depressive patients frequently complain of symptoms of
ANS dysfunction, such as dry mouth, diarrhea, and insomnia. These clinical
observations propose the assumption of altered autonomic dysfunction in these
patients. In contrast to these clinical assumptions, inconsistent results have
been found in studies of HRV in depressive patients. This work therefore covers a
brief review of the literature in respect to bipolar disorder and the rationale
to study autonomic changes in such a psychiatric disease. CONCLUSIONS:
Prospective studies of cardiovascular changes in mania and depression are needed
to evaluate a psychopathological state in connection with cardiovascular changes
and cardiac morbidity and mortality. These studies should consider BPV, coupling
and interaction analyses, the application of nonlinear methods, and a
multivariate approach in addition to the traditional analysis of HRV.
PMID- 17042883
TI - A novel technique to evaluate fluctuations of mood: implications for evaluating
course and treatment effects in bipolar/affective disorders.
AB - OBJECTIVES: Several psychiatric conditions are associated with frequent
fluctuations of affect. In this study, we propose a new technique to uniformly
score depression and mania objectively and use a new mathematical technique to
model the frequent fluctuations in mood using simulated data. Our main aim is to
examine the usefulness of this measure for evaluating treatment effects or course
of illness, especially in bipolar or unipolar affective illness to quantify mood
fluctuations. METHODS: We use a prototypical model, which takes into account the
mean, the standard deviation (SD) and the coefficient of variation (CV =
SD*100/mean) of the mood scores of the subjects over a user-defined period. We
utilize simulated data of subjects for euthymia, minor depression, minor mania,
severe depression, severe mania and cyclic bipolar illness (manic depression,
MDP). We propose an objective method to quantify the mood of the subjects at
weekly intervals (the interval can be user-defined) using a scale of 1-9 (1-4 =
degrees of depression, 5 = euthymia, 6-9 = degrees of mania). These scores can be
sampled according to the convenience and feasibility of the measurements, which
can be derived from various clinical scales or by observation of the subjects in
hospitals or other environments. We derive a new mathematical technique to arrive
at a normalized measure for each of these conditions of simulated data in
addition to the mean, SD and approximate entropy (ApEn). RESULTS: We utilize
three sets of data, one to train the model to classify the condition of the
subjects and the other two to test the reliability of the technique. We are able
to successfully classify the condition of the subjects over a 52-timepoint period
(length can be days or weeks depending upon the sampling rate). The New Index
(NI) correlates significantly only with the mean (r(2) = 0.78), but not with the
SD or ApEn score. CONCLUSIONS: These results indicate that it may be beneficial
to reduce data according to the techniques we propose so that there is greater
uniformity within which to compare future studies to evaluate treatment effects,
not only in rapid-cycling MDP but also in other affective disorders. This method
may be suitable for the meta-analysis of several studies, although different
scales have been used in each of those studies. Our measure derived from
simulated data has shown sufficient deviation of all the abnormal states from the
euthymic state. The advantages and pitfalls of these techniques are further
discussed to evaluate affect in various disorders. However, future prospective
studies must address the importance of this measure in comparison with mean, SD
and ApEn scores or other nonlinear measures of these time series. We are
evaluating other nonlinear dynamic models, which may provide a continuous measure
with which to identify different degrees of fluctuation of mood.
PMID- 17042884
TI - Placebo-level incidence of extrapyramidal symptoms (EPS) with quetiapine in
controlled studies of patients with bipolar mania.
AB - OBJECTIVES: To evaluate extrapyramidal symptoms (EPS), including akathisia, with
quetiapine in patients with bipolar mania. METHODS: Data were analyzed from four
similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies
evaluated quetiapine monotherapy (up to 800 mg/day) (n = 209) versus placebo (n =
198), with lithium or haloperidol monotherapy as respective active controls. Two
studies evaluated quetiapine (up to 800 mg/day) in combination with a mood
stabilizer (lithium or divalproex, QTP + Li/DVP) (n = 196) compared to placebo
and mood stabilizer (PBO + Li/DVP) (n = 203). Extrapyramidal symptoms were
evaluated using the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating Scale
(BARS), adverse event reports and anticholinergic drug usage. RESULTS: The
incidence of EPS-related adverse events, including akathisia, was no different
with quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS
related adverse events with QTP + Li/DVP (21.4%) were no different than with PBO
+ Li/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients
treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated
with lithium (n = 98) monotherapy experienced adverse events related to EPS. The
incidence of akathisia was low and similar with quetiapine monotherapy (3.3%) and
placebo (6.1%), and with QTP + Li/DVP (3.6%) and PBO + Li/DVP (4.9%). Lithium was
associated with a significantly higher incidence (p < 0.05) of tremor (18.4%)
than quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of
lithium, may have contributed to the elevated rate of tremor in patients
receiving lithium therapy. Haloperidol induced a significantly higher incidence
(p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and
extrapyramidal syndrome (35.4% versus 5.9%) than quetiapine. No significant
differences were observed between quetiapine and placebo on SAS and BARS scores.
Anticholinergic use was low and similar with quetiapine or placebo. CONCLUSIONS:
In bipolar mania, the incidence of EPS, including akathisia, with quetiapine
therapy is similar to that with placebo.
PMID- 17042885
TI - Pilot sample of very early onset bipolar disorder in a military population
moderates the association of negative life events and non-fatal suicide attempt.
AB - OBJECTIVE: To examine the moderating effects of very early onset diagnostic
status (or=6 months, were randomized to l-carnitine
(15 mg/kg/day) or placebo for 26 weeks, in conjunction with a moderately energy
restricted, low-fat diet. The primary outcome measure was weight change. RESULTS:
l-carnitine had no effect on mean weight loss compared with placebo (-1.9 kg
versus - 0.9 kg) (F = 0.778, df = 1,58, p = 0.381). The number of people in each
group able to lose any weight was identical ( = 0, p = 1.0); more patients in the
carnitine group (nine versus five) achieved a clinically significant weight loss
(>or=5%) but this was not statistically significant (p = 1.0, Fisher's exact
test). CONCLUSIONS: At the dose prescribed in this study carnitine
supplementation did not improve weight loss outcomes in valproate-treated bipolar
patients consuming an energy-restricted, low-fat diet.
PMID- 17042890
TI - Cognitive-behavioral therapy for bipolar disorders in adolescents: a pilot study.
AB - OBJECTIVES: To develop a cognitive behavioral intervention for adolescents with
bipolar disorders, test its feasibility and preliminary efficacy. METHODS: Based
on existing research, a manualized, individually delivered cognitive behavioral
intervention was developed and tested with adolescents with bipolar disorders as
an adjunct to pharmacological treatment. Using existing data, baseline
characteristics and outcome were compared to a matched group of eight adolescents
with bipolar disorders who did not receive any psychosocial intervention.
RESULTS: Preliminary results support the feasibility and efficacy of this
manualized cognitive behavioral intervention. CONCLUSIONS: Individually delivered
cognitive-behavioral therapy (CBT) as an adjunct to pharmacological treatment is
feasible and associated with symptom improvement in adolescents with bipolar
disorders. Randomized controlled studies are needed.
PMID- 17042891
TI - Aromatase inhibitors and bipolar mood disorder: a case report.
AB - OBJECTIVE: To report a case in which the aromatase inhibitor letrozole produced
irritable mood elevation followed by depression in a woman with a history of
postpartum depression. METHODS: A 60-year-old Caucasian woman who had a severe
depressive episode after the birth of her only child, 32 years earlier, was
treated successively with anastrozole and letrozole following a mastectomy,
radiotherapy and chemotherapy. RESULTS: Mrs X was prescribed anastrozole for
about 6 weeks. During this time she experienced labile mood, increased activity,
tremulousness and difficulty sleeping. These symptoms disappeared after stopping
the anastrozole. On letrozole, she developed an acute irritable activated mood
elevation, which then subsided into a prolonged major depression after withdrawal
of letrozole. These effects occurred during co-prescription of amitriptyline at a
low dose for urinary frequency. CONCLUSIONS: The present case suggests caution
may be warranted when employing aromatase inhibitors, especially in women with a
past history of postpartum affective disorder or bipolar disorder. As with
postpartum mania, the primary mechanism of the effect may be acute reduction in
circulating oestrogen levels.
PMID- 17042892
TI - Re-evaluation of randomized controlled trials of lithium monotherapy.
PMID- 17042895
TI - Exercise capacity and cardiovascular changes in patients with beta-thalassaemia
major.
AB - Despite the introduction of deferoxamine, 50% of thalassaemia major patients die
before the age of 35 years predominantly from iron induced heart failure. Indeed,
the assessment of myocardial performance may be of particular interest since it
can reveal an early myocardial dysfunction. By using impedance cardiography and
mass spectrometry, we studied the cardiac function and the oxygen extraction
ratio (O(2)ER) of 14 thalassaemic patients and 15 control healthy subjects during
an incremental cycle-ergometer test. The achieved mechanical power output and the
relative O(2) uptake did not reach any significant difference between groups. At
the highest workload, O(2)ER reached significantly higher values in thalassaemic
patients versus control subjects while the relationship between cardiac index
(CI) and O(2)ER (CI/O(2)ER) decreased showing a lower contribution of
cardiovascular system to maintain O(2) uptake. Results of this study imply that
CI/O(2)ER allows an early diagnosis of the iron induced myocardial dysfunction,
whereas it is not clinically patent yet. To our knowledge, this is the first
study revealing an O(2)ER pivotal role as compensatory mechanism to maintain a
normal working capacity in subjects suffering from thalassaemia major.
PMID- 17042896
TI - Supraorbital cutaneous blood flow rate during carotid endarterectomy.
AB - BACKGROUND: The supraorbital skin region is supplied by the supraorbital artery,
which is a branch of the internal carotid artery. The supraorbital cutaneous
blood flow rate may therefore be influenced by changes in the internal carotid
artery flow during carotid endarterectomy. METHODS: The supraorbital cutaneous
blood flow rate was measured by the application of heat to the skin and following
the subsequent dissipation of the heat in seven patients undergoing carotid
endarterectomy. At the same time, the oxygenation in the right and left frontal
region was monitored by near-infrared spectroscopy (NIRS). RESULTS: During cross
clamping of the carotid artery, the ipsilateral NIRS-determined frontal
oxygenation tended to decrease [67 +/- 13% to 61 +/- 11% (P = 0.06);
contralateral 68 +/- 11% to 66 +/- 8%] as did the supraorbital cutaneous blood
flow rate from 56 +/- 23 to 44 +/- 7 ml 100 g(-1) min(-1). With the opening of
the external carotid artery, the NIRS-determined frontal oxygenation reversed to
66 +/- 8% (P<0.05) on the ipsilateral side, with no significant change on the
contralateral side and the supraorbital cutaneous blood flow rate increased to 53
+/- 11 (P<0.05). Opening of the internal carotid artery did not significantly
affect the NIRS (67 +/- 8% and 69 +/- 9%; ipsilateral, contralateral), but the
supraorbital cutaneous blood flow rate increased to 88 +/- 10 ml 100 g(-1) min(
1) (P<0.001). CONCLUSION: Cross-clamping of the internal carotid artery affects
the supraorbital cutaneous blood flow rate as well as the frontal lobe
oxygenation.
PMID- 17042898
TI - Signal quality in a three-channel ambulatory electrocardiographic monitoring
system.
AB - BACKGROUND: Ambulatory electrocardiographic recordings are not infrequently
hampered by technical artefacts. Verification of good original signal level and
an adequate number of ECG channels should enhance the quality. METHODS: Data from
all three-channel (mV5, mV1, III) recordings in Peijas hospital during one
calendar year were prospectively collected. A total of 255 recordings (24 h n =
239, and 48 h n = 16) made for 247 patients were analysed. Relative signal
strength number (integer scale 5-0) was registered during hook-up. Final quality
of recordings were afterwards evaluated with a three-point semi-quantitative
scale by an experienced physician. RESULTS: The signal strength number was
adequate (>or=3) in all 241 available cases. Distribution of signal strength did
not significantly vary between ECG channels. The overall quality of recordings
was 'good' in three-fourth of the cases and only were they seldom 'poor'. Signal
strength and quality ratings were not significantly interrelated. The quality
was, as expected, better in 24 h recording than in 48 recordings, and it was also
better in channel III than in channel mV5. CONCLUSIONS: The original signal
strength level (impedance) is not a crucial fact in ambulatory
electrocardiographic recordings as long as it is within (specified) acceptable
limits. In terms of quality, a third (inferior) ECG channel is recommendable.
PMID- 17042897
TI - Effect of adrenergic blockade on plasma adrenomedullin concentration during
static handgrip in patients with heart failure.
AB - Our previous study showed that static handgrip caused increases in the plasma
adrenomedullin (ADM) both in patients with heart failure (HF) and healthy
subjects. The present study was designed to determine the role of the sympathetic
nervous system in mediating plasma ADM changes during handgrip in patients with
HF. Twelve male HF patients (II class NYHA) treated with carvedilol, a non
selective adrenergic blocker (TC) and 12 patients untreated with carvedilol (UC)
performed two 3-min bouts of static handgrip at 30% of maximal voluntary
contraction, alternately with each hand. At the end of both exercise bouts and in
5 min of the recovery period, plasma ADM and catecholamines were determined. In
addition, heart rate, blood pressure and stroke volume (SV) were measured. The
baseline plasma ADM, noradrenaline (NA) and adrenaline (A) levels were similar in
the two groups of patients, while SV was higher (P<0.05) in TC than in UC. During
exercise plasma ADM concentrations were lower (P<0.05) in TC than in UC, but the
handgrip-induced increases in plasma ADM did not differ between the groups.
Plasma ADM correlated with NA concentrations (r = 0.764) and with SV (r = -0.435)
and increases in plasma ADM expressed as percentage of baseline values correlated
with those of plasma NA (r = 0.499), diastolic BP (r = 0.550) and total
peripheral resistance (r = 0.435). The study suggests that the sympathetic
nervous system may be involved in the stimulation of ADM secretion during static
exercise either directly or by changes in the haemodynamic response.
PMID- 17042899
TI - Pre- and postoperative evaluation of the metabolic activity in muscles associated
with ruptured rotator cuffs by F-FDG PET imaging.
AB - We examined uptake of 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) using positron
emission tomography (PET) into the bilateral shoulder muscles of four patients
before and after unilateral rotator cuff repair. The relative ratio of the
subtracted standardized uptake value on the supraspinatus with a torn
supraspinatus tendon to that of the subscapularis on the ipsilateral side was
significantly lower than that on the normal side (0.69 +/- 0.05 versus 1.06 +/-
0.36). The relative ratio of the infraspinatus on the rupture side was also
significantly lower than that on the normal side (0.91 +/- 0.09 versus 1.41 +/-
0.35). However, by 6 months postoperative, the reduced glucose metabolism in
these muscles had recovered to the same levels as those on the normal side. As
indicated by FDG PET, muscle metabolism in rotator cuff tears was reduced,
subsequently recovering to the level of the normal side after operative repair.
PMID- 17042900
TI - Subendocardial versus transmural ischaemia in myocardial perfusion SPECT--a Monte
Carlo study.
AB - Myocardial perfusion imaging with single-photon emission computed tomography
(SPECT) is useful for the evaluation of patients with known or suspected coronary
artery disease. Parameters of interest are the reduction in the blood perfusion
(severity) and the lesion volume (extent). The aim of this study was to evaluate
these parameters, as calculated by automatic quantification software, for
different cases of subendocardial and transmural myocardial lesions. METHODS: A
computer phantom was used to simulate 32 male patients with different defect
locations and activity uptakes, which were based on clinical patient studies. The
Monte Carlo program SIMIND was used to simulate realistic SPECT projections which
were reconstructed to give short-axis images, analysed by the AutoQUANT program
using the same procedure as for a real patient. RESULTS: The results showed a
disparity between the quantification of transmural and subendocardial lesions
with the same lesion activity uptake reduction and this could be confirmed by
visual interpretation. Neither the parameters given by the quantification program
nor visual interpretation could distinguish between the transmural lesions and
the subendocardial lesions with activity uptake reduction twice as high as in the
corresponding transmural lesions. CONCLUSION: Transmural lesions and the
corresponding subendocardial lesions with the same activity uptake reduction
could be separated by the quantification software for SPECT imaging and visual
analysis. The subendocardial lesions with activity uptake reduction twice as high
as in the corresponding transmural lesions could not be differentiated neither by
the quantification software nor by visual interpretation. Thus these lesions will
get the same scoring when analysed by the AutoQUANT program.
PMID- 17042901
TI - Acute administration of a single dose of valsartan improves left ventricular
functions: a pilot study to assess the role of tissue velocity echocardiography
in patients with systemic arterial hypertension in the TVE-valsartan study I.
AB - BACKGROUND: The advent of colour-coded tissue velocity echocardiography (TVE) has
now made it possible to quantify left ventricular (LV) functions in patients with
systemic arterial hypertension (HTN). Hypothesis In this project, we have studied
the cardiac effects of a single dose of orally administered valsartan in patients
with known HTN. METHODS: Fifty-five patients with HTN with a mean age of 56 +/-
10 years were given an early morning dose of 80 mg valsartan withholding regular
antihypertensive medications on the day of investigation. TVE images, acquired on
VIVID systems were digitized for postprocessing of longitudinal and radial peak
systolic velocities, strain rate, and systolic and diastolic time intervals
before (pre) and 5 h after (post) administration of the drug. RESULTS: Blood
pressure (mmHg) pre and post, respectively, were 147 +/- 15 versus 137 +/- 14
systolic and 90 +/- 7 versus 86 +/- 7 diastolic (all P<0.01). LV longitudinal
systolic velocities (cm s(-1)) were significantly higher post in LV septum (5.7
+/- 1.1 versus 6.4 +/- 1.6; P<0.001) with similar results obtained in other LV
walls. Radial strain rate (1 s(-1)) was significantly higher post compared with
pre valsartan (2.1 +/- 0.6 versus 2.3 +/- 0.9; P<0.01). Regional diastolic
filling and ejection times (ms) were significantly shorter post (390 +/- 122
versus 370 +/- 120 and 275 +/- 32 versus 163 +/- 36 respectively; all P<0.05).
CONCLUSIONS: Within 5 h after oral administration of valsartan, improvement in
regional myocardial systolic functions could be registered. Although the changes
could well be secondary to afterload reduction, additional effects of the drug,
evidenced by improved strain rate that is relatively load-independent, may have
contributed in this improvement.
PMID- 17042902
TI - Surfactant as a carrier: influence of immunosuppressive agents on surfactant
activity.
AB - INTRODUCTION: It has been proposed that exogenous pulmonary surfactant can be
used as a drug delivery system for immunosuppressive agents to the alveolar
compartment of the lung while reducing the risk of systemic toxicity. Before
using this combination, however, alterations in activity of both substances
should be examined. Therefore, this study investigated whether the activity of a
natural derived surfactant preparation is changed after it is mixed with
cyclosporine A (CsA) or rapamycin (RPM). METHODS: A surfactant suspension was
mixed with CsA or RPM and minimal surface tension of these mixtures was measured
in vitro. Surfactant activity was evaluated in vivo by its capacity to restore
gas exchange in an established model of surfactant deficiency in rats. CsA
surfactant, RPM-surfactant or surfactant alone was instilled intratracheally and
blood gases were measured under standardized ventilatory conditions. RESULTS:
Minimal surface tension of surfactant-CsA was comparable with that of surfactant
alone, whereas minimal surface tension of the surfactant-RPM mixture was
increased. In vivo partial arterial oxygen pressure levels increased immediately
to prelavage values after instillation of CsA-surfactant, RPM-surfactant and
surfactant only and were comparable during the entire study period. CONCLUSION:
The activity of a naturally derived surfactant was affected when mixed with RPM
but not when mixed with CsA at the used concentrations.
PMID- 17042903
TI - Non-dipolar content of the T-wave as a measure of repolarization inhomogeneity in
ST-elevation myocardial infarction.
AB - The non-dipolar content of the T-wave, i.e. the component of the signal, which
cannot be explained by a dipolar model, has been suggested as a measure of the
local repolarization inhomogeneity. Our purpose was to study the non-dipolar
content of the T-wave during the initial course of ST-elevation myocardial
infarction (STEMI), when local repolarization inhomogeneity presumably is
markedly increased. Twelve-lead ECG was semicontinuously collected in 211
patients with STEMI, treated with a thrombolytic agent. The T-wave was processed
by principal component analysis. The absolute and relative T-wave residues were
used as measures of the non-dipolar content. The median values for each hour and
for the entire monitoring time were computed. Changes in the parameters were
closer studied in two windows, 0-10 respectively, 11-24 h after start of ECG
monitoring. The median of the absolute T-wave residue during the entire
monitoring period was 25 000 units in the STEMI-group and 13 500 units in the
comparison group. The median for hour 1 was 36 500 units and 28 800 units for
hour 2. The decrease was greater in patients with >or=50% resolution of the ST
elevation at 60 min. The moment of change, identified by cumulative sum-method,
showed no correlation to the time for 50% ST-resolution. We conclude, that
patients with thrombolysed STEMI have an increased non-dipolar content of the T
wave. Resolution of the ST-elevation is associated with a decrease. The increased
non-dipolar content reflects a property of the repolarization phase, which is
related to but separated from the ST-elevation.
PMID- 17042904
TI - Liver-type fatty acid binding protein in serum and broncho-alveolar lavage in a
model of acute respiratory failure because of surfactant depletion--a possible
marker for lung damage?
AB - INTRODUCTION: Liver-type fatty acid binding proteins (L-FABP) have been shown to
be present in alveolar macrophages and type II pneumocytes of the lung. This
study determined levels of L-FABP in serum and broncho-alveolar lavage (BAL)
during experimental acute respiratory failure (ARF) to evaluate whether this
molecule can serve as a marker for lung damage. METHODS: Male Sprague-Dawley rats
(n = 24) were ventilated and either lung lavaged or lavaged and treated with
surfactant, and compared to ventilated, non-lavaged controls. Blood samples were
drawn every hour for 4 h to measure L-FABP concentrations in serum. At the end of
the experiment a BAL was performed to determine L-FABP levels in BAL fluid. L
FABP was measured with a sandwich enzyme-linked immunosorbent assays. RESULTS:
Serum L-FABP concentrations rose significantly during the first 2 h of
ventilation in all groups compared with baseline values. After 2 h L-FABP levels
were significantly higher in lavaged animals compared with the ventilated
controls and to animals treated with surfactant. After 4 h of ventilation, L-FABP
in BAL was significantly higher in lavaged, non-surfactant treated animals
compared with the ventilated controls. CONCLUSION: In the early phase of
experimental ARF serum L-FABP levels correlate well with the degree of lung
injury.
PMID- 17042905
TI - Early recovery from post-traumatic acute respiratory distress syndrome.
AB - BACKGROUND: To present and discuss the rationale and possible benefits of timely
alveolar recruitment in early post-traumatic acute respiratory distress syndrome.
METHODS: A 17-year-old patient who had sustained blunt thoracic trauma presented
with severe hypoxaemia on admission and whole body computed tomography showed
pulmonary contusion and substantial bilateral atelectasis. Oxygenation and lung
mechanics did not improve with low tidal volume ventilation using high positive
end-expiratory pressures (PEEPs). Therefore we applied an alveolar recruitment
manoeuvre 7 h after admission. After alveolar recruitment, PEEP was titrated to
the lowest level which prevented alveolar derecruitment. RESULTS: Oxygenation and
lung compliance improved rapidly and aeration of the entire lung was confirmed by
computed tomography 27 h after the recruitment manoeuvre. The patient recovered
completely and was discharged after 17 days. CONCLUSION: Although robust evidence
is still lacking, several lines of evidence suggest potential benefits of timely
alveolar recruitment. Patients with early post-traumatic respiratory failure seem
to most readily respond to alveolar recruitment manoeuvres and could thus benefit
from the gain in functional lung volume and oxygenation. Moreover the probability
of ventilator associated complications may be reduced.
PMID- 17042906
TI - The acute effects of different whole body vibration amplitudes on the endocrine
system of young healthy men: a preliminary study.
AB - Whole body vibration (WBV) has been suggested as an alternative form of exercise
producing adaptive responses similar to that of resistance training. Very limited
information is available on the effects of different vibration parameters on
anabolic hormones. In this study, we compared the acute effects of different WBV
amplitudes on serum testosterone (T) and insulin growth factor-1 (IGF-1). Nine
healthy young recreationally active adult males (age 22 +/- 2 years, height 181
+/- 6.3 cm, weight 77.4 +/- 9.5 kg) voluntarily participated in this randomized
controlled (cross-over design) study. The subjects performed 20 sets of 1 min
each of WBV exercise in the following conditions: Non-vibration condition
(control), low amplitude vibration [low (30 Hz, 1.5 mm peak-to-peak amplitude)]
and high amplitude vibration [high (30 Hz, 3 mm peak-to-peak amplitude)]. Blood
samples were collected before, after 10 sets, at the end (20th set) and after 24
h of the exercise bout. WBV exercise did not produce significant changes in serum
T and IGF-1 either with low or high amplitude when compared with the control
condition. The results of this study demonstrate that a single session of WBV
exposure with a frequency of 30 Hz and amplitudes of 1.5 and 3 mm does not
noticeably alter serum T and IGF-1 levels.
PMID- 17042907
TI - Phenotyping the level of blood pressure by telemetry in mice.
AB - 1. Using telemetry, arterial blood pressure (BP) can be measured directly over
long periods in freely behaving animals without recent anaesthesia or surgery. In
the present review, we discuss the strengths and limitations of this method and
important considerations in using the method to characterize the BP level in
mice. 2. A variety of informative statistics can be used to describe the BP level
and we have made available a spreadsheet template for their calculation on a
routine basis. The BP level is well summarized using the average value for an
entire 24 h period or for the individual light and dark phases of the day. Such
long-term averages exhibit less statistical variation than those of short
recording periods. In addition, averages of the dark and light phases of the day
convey information concerning circadian variations of BP. 3. The frequency
distribution of BP samples provides additional information concerning the range
of BP values recorded over the course of the day and can be described in terms of
percentiles of the distribution that correspond with the minimum and maximum BP
values and their span. 4. In mice, BP can be markedly affected by locomotor
activity cycles that occur frequently throughout both the light and dark phases
of the day. In addition, BP is strongly affected by ambient temperature and food
intake, as well as potentially by other determinants of energy balance.
Consideration of these factors may help improve accuracy and precision when
phenotyping the BP level in mice.
PMID- 17042908
TI - Comparison of the effects of tulobuterol patch and salmeterol in moderate to
severe asthma.
AB - 1. Although the clinical effects of the tulobuterol patch have been reported to
include an increase in morning peak expiratory flow (PEF) values and a decrease
of symptoms and the frequency of the rescue use of inhaled short-acting beta2
adrenoceptor agonists, no trials comparing the efficacy of the tulobuterol patch
to other standard inhaled long-acting beta2-adrenoceptor agonists have yet been
conducted. The aim of the present study was to compare the clinical effects of
the patch formulation of tulobuterol with those of inhaled salmeterol in moderate
to severe asthma. 2. Fifty-four patients with moderate to severe asthma, whose
conditions were suboptimally controlled despite receiving inhaled
corticosteroids, were recruited. The study was a prospective, randomized trial of
cross-over design comparing the effects of 4 weeks treatment with tulobuterol
patch, 2 mg once daily, and salmeterol, 50 mg twice daily. The mean
prebronchodilator morning PEF during the last 14 days of each treatment period
and health-related quality of life (HRQoL) were the primary outcome variables.
The HRQoL was assessed using the St George's Respiratory Questionnaire. 3. Forty
four patients (81.5%) completed the trial and were included in the analysis. The
mean morning PEF and HRQoL score were significantly improved in both the
salmeterol (P < 0.0001 and P < 0.05, respectively) and the tulobuterol patch (P <
0.01 and P < 0.05, respectively) treatment periods compared with the run-in
period. Although the mean morning PEF was significantly higher in the salmeterol
treated group than in the tulobuterol-treated group (P < 0.001), the HRQoL scores
were comparable. 4. The tulobuterol patch may be useful as a controller
medication in addition to inhaled corticosteroids in moderate to severe asthma.
PMID- 17042909
TI - Effects of trolox on nerve dysfunction, thermal hyperalgesia and oxidative stress
in experimental diabetic neuropathy.
AB - 1. Diabetic neuropathy is one of the most common complications of diabetes and
oxidative stress has been implicated to play a major role in its pathophysiology.
2. In the present study, we targeted oxidative stress using trolox, an anti
oxidant, in streptozotocin-induced diabetic neuropathy in rats. 3. Compared with
control rats, diabetic rats showed significant deficits in motor nerve conduction
velocity (MNCV; 49.91 +/- 1.94 vs 42.77 +/- 1.39 m/s, respectively) and nerve
blood flow (NBF; 107.98 +/- 8.22 vs 38.9 +/- 2.7 arbitarary perfusion units,
respectively) after 8 weeks of diabetes. Tail flick latencies for cold and hot
immersion tests were also significantly reduced in diabetic rats, indicating
thermal hyperalgesia. These observations indicate development of diabetic
neuropathy. 4. A significant decrease in the activity of anti-oxidant enzymes
(superoxide dismutase and catalase) and an increase in lipid peroxidation were
observed in sciatic nerves from diabetic rats compared with age-matched control
rats. Alterations in the activity of anti-oxidant enzymes and lipid peroxidation
in diabetic rats indicate oxidative stress in diabetic neuropathy. 5. Two weeks
treatment with trolox (10 and 30 mg/kg, i.p.) started on completion of the 6th
week of diabetes significantly improved MNCV, NBF and inhibited thermal
hyperalgesia. Trolox treatment also improved the activity of anti-oxidant enzymes
and inhibited lipid peroxidation in sciatic nerves of diabetic rats. 6. The
results of the present study suggest the beneficial effects of trolox in
experimental diabetic neuropathy.
PMID- 17042910
TI - Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the
rat.
AB - 1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial
dysfunction associated with nitric oxide (NO) deficiency and increased superoxide
(O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have
been reported to improve endothelial function through increased availability of
NO and reduced O2- production in various forms of hypertension. In the present
study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent
endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague
Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were
treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days.
Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in
Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood
pressure (SBP) was measured on alternate days using the tail-cuff method.
Endothelial function was assessed by acetylcholine-induced vasorelaxation and
phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was
assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3.
In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2
mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP
was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P <
0.001), but was significantly lower than SBP in the group treated with Dex alone
(P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were
greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P <
0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato
group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment
with Ato improved endothelial function, reduced superoxide production and reduced
SBP in Dex-treated SD rats.
PMID- 17042911
TI - Edaravone reduces myocardial infarct size and improves cardiac function and
remodelling in rabbits.
AB - 1. In the present study, we investigated the effect of 3-methyl-1-phenyl-2
pyrazolin-5-one (edaravone), a free radical scavenger, on myocardial infarct (MI)
size and cardiac function in an in vivo model of MI in rabbits. We further
investigated the contribution of hydroxyl radicals, superoxide and nitric oxide
(NO) to its effects. 2. Anaesthetized open-chest Japanese white male rabbits were
subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n
= 10) was injected with saline 10 min before reperfusion. The edaravone group (n
= 10) was injected with a bolus of 3 mg/kg edaravone 10 min before reperfusion.
The edaravone + N(G)-nitro-L-arginine methyl ester (L-NAME) group (n = 5) was
given 10 mg/kg, i.v., L-NAME 10 min before the administration of 3 mg/kg
edaravone. The L-NAME group (n = 5) was given 10 mg/kg, i.v., L-NAME 20 min
before reperfusion. Infarct size was measured using the triphenyl tetrazolium
chloride method and is expressed as a percentage of area at risk. Cardiac
function was assessed by echocardiography 14 days after infarction. 3. In another
series of experiments, rabbits were subjected to 30 min coronary occlusion and 30
min reperfusion and myocardial interstitial 2,3-dihydroxybenzoic acid (DHBA) and
2,5-DHBA levels, indicators of hydroxyl radical, were measured using a
microdialysis technique. 4. Infarct size in the edaravone group was significantly
reduced compared with that in the control group (27.4 +/- 6.8 vs 43.4 +/- 6.8%,
respectively; P < 0.05). The edaravone-induced reduction of infarct size was
abolished by pretreatment with L-NAME. Myocardial interstitial levels of 2,3-DHBA
and 2,5-DHBA increased 20 and 30 min after ischaemia and peaked at 10 min
reperfusion in the control group. Edaravone significantly inhibited the increase
in 2,3-DHBA and 2,5-DHBA levels seen during reperfusion. Dihydroethidium staining
showing in situ detection of superoxide was less intense in ischaemic myocardium
in the edaravone-treated group compared with the control group. Edaravone
improved cardiac function and left ventricular remodelling 14 days after
infarction. 5. In conclusion, edaravone significantly reduces MI size and
improves cardiac function and LV remodelling by decreasing hydroxyl radicals and
superoxide in the myocardium and increasing the production of NO during
reperfusion in rabbits.
PMID- 17042912
TI - D-dopa is unidirectionally converted to L-dopa by D-amino acid oxidase, followed
by dopa transaminase.
AB - 1. Many studies have shown that administration of d-3, 4-dihydroxyphenylalanine
(D-dopa) produces contralateral rotation in hemi-parkinsonian animals comparable
to L-dopa, with less potency and slower onset. It was postulated that D-dopa was
converted to L-dopa to produce these effects. 2. To investigate the postulated
chiral inversion of D-dopa to L-dopa and the related mechanism, an enantiomeric
separation method for D- and L-dopa using HPLC was first established. Then, rat
kidney homogenates containing D-dopa or L-dopa were incubated and subjected to
HPLC to detect traces of respective enantiomer generation. The mechanism of the
chiral inversion of d-dopa was explored by direct measurement of the production
of L-dopa in kidney homogenates. D-dopa incubations containing different
concentrations of an inhibitor of D-amino acid oxidase (DAAO) and an inhibitor of
dopa transaminase were measured for L-dopa generation using HPLC. The role of
DAAO in the chiral inversion of D-dopa to L-dopa was further investigated by
using purified DAAO and mutant ddY/DAAO- mouse kidney lacking DAAO activity. 3.
In rat kidney homogenate, D-dopa was, indeed, converted to L-dopa, whereas L-dopa
was not converted to D-dopa. Sodium benzoate, a selective inhibitor of DAAO,
blocked L-dopa generation in a concentration-dependant manner. In contrast with
kidney homogenates of wild-type ddY/DAAO+ mice, those of mutant ddY/DAAO- mice
lacking DAAO activity did not convert D-dopa to L-dopa unless exogenous DAAO
protein was added. Conversely, when carbidopa, an inhibitor of dopa transaminase,
was added to the homogenates, significant inhibition of L-dopa production was
noted. 4. These results prove the proposal that d-dopa undergoes unidirectional
chiral inversion and further suggest that D-dopa is first oxidatively deaminated
by DAAO to its alpha-keto acid and then transaminated by dopa transaminase to L
dopa.
PMID- 17042913
TI - Sertraline protects against monocrotaline-induced pulmonary hypertension in rats.
AB - 1. Serotonin (5-HT), as a type of mitogen for smooth muscle cells, plays an
important role in the development of pulmonary hypertension. It is known that
selective serotonin re-uptake inhibitors (SSRI) inhibit 5-HT internalization.
Therefore, the aim of the present study was to investigate the protective effect
and mechanism of the SSRI sertraline against pulmonary hypertension. 2.
Monocrotaline (MCT)-induced chronic 'inflammatory' pulmonary hypertension in
Wistar rats was established. Pulmonary haemodynamic measurement and lung tissue
morphological investigations were undertaken. Serotonin transporter (SERT) mRNA
was assayed by reverse transcription-polymerase chain reaction (RT-PCR). 3. The
results showed that pulmonary artery pressure (PAP) was significantly increased
by MCT treatment from 12.6 +/- 2.1 to 20.1 +/- 3.4 mmHg (P < 0.01 vs control) and
sertraline attenuated the MCT-induced increase in PAP from 20.1 +/- 3.4 to 16.4
+/- 1.8 mmHg (P < 0.05 vs MCT). The right ventricular index was increased in the
MCT-treated group from 0.32 +/- 0.04 to 0.51 +/- 0.09 (P < 0.01 vs control) and
was reduced to 0.42 +/- 0.04 by sertraline (P < 0.05 vs MCT). The degree of
muscularization of the pulmonary artery in the MCT-treated group was
significantly higher than control (P < 0.01) and was decreased by sertraline (P <
0.01 vs MCT). The RT-PCR assay showed that MCT increased SERT mRNA expression
from 0.86 +/- 0.08 to 0.99 +/- 0.06 (P < 0.05 vs control), which was attenuated
by sertraline (0.82 +/- 0.09; P < 0.05 vs MCT). 4. In conclusion, the SSRI
sertraline protects against MCT-induced pulmonary hypertension by decreasing PAP,
right ventricular index and pulmonary artery remodelling, which may be related to
a reduction in SERT mRNA.
PMID- 17042914
TI - Rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, reduces
infarction volume and neurological deficits in an embolic model of stroke.
AB - 1. Stroke is accompanied by a robust inflammatory response, glutamate-mediated
excitotoxicity, release of reactive oxygen species and apoptosis.
Thiazolidinediones, which target the nuclear receptor peroxisome proliferator
activated receptor (PPAR)-g, have been reported recently to exhibit potent anti
inflammatory and anti-oxidant actions and inhibit both neural excitotoxicity and
apoptosis. 2. The present study was conducted to determine whether rosiglitazone,
a potent thiazolidinedione for PPAR-g, would show efficacy against the cerebral
infarction and neurological dysfunctions induced by embolic middle cerebral
artery (MCA) occlusion in the rat. 3. Focal ischaemic injury was induced by
embolizing a preformed clot into the MCA. Rosiglitazone was dissolved in dimethyl
sulphoxide and injected i.p. 1 h before MCA occlusion at doses of 0.33, 0.1, 0.3
or 1 mg/kg. In addition, 1 mg/kg rosiglitazone was used immediately or 4 h after
embolization. Forty-eight hours after MCA occlusion, brains were removed,
sectioned and stained with a 2% solution of 2,3,5-triphenyltetrazolum chloride
and analysed using a commercial image-processing software program. 4. When
rosiglitazone was administered 1 h before embolization, it significantly reduced
infarct volume by 48.2, 68.4% and 70.3% at doses of 0.1, 0.3 and 1 mg/kg,
respectively (P < 0.001). Administration of rosiglitazone (1 mg/kg) immediately
or 4 h after stroke also reduced infarct volume by 67 and 50.8%, respectively (P
< 0.001). Rosiglitazone-treated rats also demonstrated improved neurological
functions. However, there were no statistically significant differences between
control and treated groups in terms of brain oedema at 48 h after ischaemic
injury. 5. The findings of the present study may support the idea of a potential
benefit of thiazolidinediones in the management of ischaemic stroke.
PMID- 17042915
TI - Altering extracellular potassium concentration does not modulate drug block of
human ether-a-go-go-related gene (hERG) channels.
AB - 1. Drug-induced block of the rapidly activating delayed rectifier K+ current
(I(Kr)), encoded by human ether-a-go-go-related gene (hERG), has been linked to
acquired long QT syndrome (aLQTS). Hypokalaemia is a recognized risk factor in
aLQTS. To further understand why hypokalaemia is a risk factor in aLQTS, we
examined the effect of [K+]o on drug block of the hERG potassium channel stably
expressed in human embryonic kidney (HEK-293) cells using whole-cell voltage
clamp techniques. 2. The effects of selected [K+]o (1-20 mmol/L) on hERG block
with four structurally diverse compounds (dofetilide, mesoridazine, quinidine and
terfenadine) from different therapeutic classes were evaluated. Reducing [K+]o
from 20 to 1 mmol/L had little effect on IC50 values for hERG current block for
all four compounds. For example, evaluating quinidine in external potassium
concentrations of 20, 10, 5 and 1 mmol/L resulted in IC50 values of 1.82 +/-
0.33, 2.04 +/- 0.28, 1.57 +/- 0.52 and 1.14 +/- 0.21 mmol/L, respectively. No
statistically significant difference (P > 0.35, anova) was observed between drug
block of hERG in different external potassium concentrations. These data are in
contrast with previously reported results examining hERG channel modulation
expressed in AT-1 cells under similar experimental conditions. 3. These results
demonstrate that [K+]o does not directly modulate drug block of hERG channels
expressed in an HEK-293 cell line. The enhanced risk of Torsades de Pointes
associated with hypokalaemia in aLQTS may be due to reduction of other (non-hERG)
potassium currents, further reducing the repolarization reserve, and not due to
direct modulation of hERG block by [K+]o.
PMID- 17042916
TI - CPU0507, an endothelin receptor antagonist, improves rat hypoxic pulmonary artery
hypertension and constriction in vivo and in vitro.
AB - 1. The Aim Of The Present Study Was To Test The Efficacy Of The Novel Endothelin
(Et) Receptor Antagonist CPU0507 In Treating Rat Hypoxic Pulmonary Hypertension
(Ph) In Vivo And In Vitro And To Explore The Role Of The Et-1 System In The
Disease. 2. Male Sprague-dawley Rats (220 +/- 20 G) Were Divided Into Four
Groups: (I) Control; (Ii) Untreated Hypoxic (28 Days Hypoxia); (Iii) Hypoxic Rats
Treated In The Last 5 Days Of Hypoxia With Nifedipine(5 Mg/kg Per Day, P.o.); And
(Iv) Hypoxic Rats Treated In The Last 5 Days Of Hypoxia With CPU0507 (20 Mg/kg
Per Day, S.c.). Effects Of Treatments On Haemodynamics And Biochemical Data, As
Well As Functional Assessments Of The Isolated Pulmonary Artery, Were Determined
In Vivo And In Vitro. 3. It Was Found That CPU0507 Reduced The Elevated Pulmonary
Arterial Pressure And Right Heart Weight Index And Restored Abnormalities In
Nitric Oxide (No), Malondialdehyde And No Synthase (Nos) In The Serum And
Superoxide Dismutase, Hydroxyproline And Nos In Pulmonary Homogenates. In
Addition, CPU0507 Restored Altered Pulmonary Vasoconstrictor And Vasodilator
Responses. Vascular Constriction And Dilatation Of Untreated Pulmonary Arteries
Were Reverted Effectively Towards Normal Following Exposure Of Artery Rings To
CPU0507 In Vitro. 4. In Conclusion, The Results Indicate That Hypoxic Ph Is
Relieved Significantly By CPU0507 In Vivo And In Vitro And The Effects Are
Presumed To Be Mediated By Suppression Of The Et-reactive Oxygen Species Axis.
PMID- 17042917
TI - N(G)-nitro-L-arginine methyl ester potentiates anaphylactic venoconstriction in
rat perfused livers.
AB - 1. The effects of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine
methyl ester (L-NAME) on anaphylaxis-induced venoconstriction were examined in
rat isolated livers perfused with blood-free solutions in order to clarify the
role of NO in anaphylactic venoconstriction. 2. Rats were sensitized with
ovalbumin (1 mg) and, 2 weeks later, livers were excised and perfused portally in
a recirculating manner at a constant flow with Krebs'-Henseleit solution. The
antigen (ovalbumin; 0.1 mg) was injected into the reservoir 10 min after
pretreatment with L-NAME (100 micromol/L) or D-NAME (100 micromol/L) and changes
in portal vein pressure (Ppv), hepatic vein pressure (Phv) and perfusate flow
were monitored. In addition, concentrations of the stable metabolites of NO ( and
) were determined in the perfusate using an HPLC-Griess system. 3. The antigen
caused hepatic venoconstriction, as evidenced by an increase in Ppv from a mean
(SEM) baseline value of 7.7 +/- 0.1 cmH2O to a peak of 21.4 +/- 1.1 cmH2O at 3
min in D-NAME-pretreated livers. Pretreatment with L-NAME augmented anaphylactic
venoconstriction, as reflected by a higher Ppv (27.4 +/- 0.8 cmH2O) after antigen
than observed following D-NAME pretreatment. The addition of L-arginine, a
precursor for the synthesis of NO, reversed the augmentation of anaphylactic
venoconstricion by L-NAME. This suggests that hepatic anaphylaxis increased the
production of NO, which consequently attenuated anaphylactic venoconstriction.
However, perfusate NOx levels did not increase significantly after antigen in
livers pretreated with either L-NAME or D-NAME. 4. In conclusion, L-NAME
potentiates rat anaphylactic hepatic venoconstriction, suggesting that NO
contributes to the attenuation of the venoconstriction. However, this functional
evidence was not accompanied by corresponding changes in perfusate NOx
concentrations.
PMID- 17042918
TI - Kynurenine pathway metabolism in patients with osteoporosis after 2 years of drug
treatment.
AB - 1. Metabolism of tryptophan along the oxidative pathway via kynurenine results in
the production of quinolinic acid and kynurenic acid, which can act on glutamate
receptors in peripheral tissues. We have now measured the concentrations of
kynurenine pathway metabolites in the plasma of patients with osteoporosis before
treatment with drugs, throughout and after 2 years of treatment with the drugs
raloxifene or etidronate. Oxidative stress was assessed by measuring levels of
the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Kynurenines
were analysed by HPLC. Bone density was measured using dual-energy X-ray
absorptiometry scans. 2. Patients with osteoporosis showed significantly lower
baseline levels of 3-hydroxyanthranilic acid compared with healthy controls, but
significantly higher levels of anthranilic acid and lipid peroxidation products.
After 2 years treatment with etidronate and calcium, we observed significant
therapeutic responses quantified by bone densitometric scanning. Significant
improvements were not seen in patients treated with raloxifene. 3. In parallel,
the levels of 3-hydroxyanthranilic acid, anthranilic acid and lipid peroxidation
products were restored to control values by both drug treatments studied and
tryptophan levels were increased significantly compared with baseline values. 4.
The results suggest that tryptophan metabolism is altered in osteoporosis in a
manner that could contribute to the oxidative stress and, thus, to progress of
the disease. The oxidative metabolism of tryptophan (the kynurenine pathway)
could represent a novel target for the development of new drugs for the treatment
of osteoporosis. In addition, we noted that etidronate is a more effective drug
than raloxifene, but that the simultaneous use of non-steroidal anti-inflammatory
drugs may reduce the efficacy of etidronate.
PMID- 17042919
TI - Voltage and ionic regulation of human serotonin transporter in Xenopus oocytes.
AB - 1. The serotoninergic system is known to be involved in the control of multiple
behavioural and physiological functions. The serotonin (5-hydroxtryptamine; 5-HT)
transporter (SERT), which controls the synaptic 5-HT concentration through re
uptake of this neurotransmitter into presynaptic terminals, has been a primary
therapeutic target for various psychiatric and peripheral disorders. The aim of
the present study was to identify the regulatory mechanism(s) of the human SERT
(hSERT) in heterologously expressed oocytes. 2. The hSERT cRNA was transcribed in
vitro and injected into Xenopus oocytes. The 5-HT-induced transporter currents
were measured by voltage clamp. The effects of extracellular sodium or chloride
were studied by replacement perfusion with tetramethylammonium-chloride (96
mmol/L) or sodium acetate (96 mmol/L). In addition, to alter the internal calcium
concentration, CaCl2 (50 micromol/L) and inositol triphosphate (IP3; 50
micromol/L), with or without EGTA (2.5 mmol/L), were injected into oocytes. The
specificity of 5-HT-sensitive currents was determined by the use of the SERT
antagonist desipramine and niflumic acid to block background chloride currents.
3. The hSERT-expressing oocytes displayed voltage-dependent, 5-HT-induced
currents that increased at negative potentials. Replacing extracellular sodium or
chloride significantly decreased the hSERT currents by 89 and 45%, respectively
(P < 0.05, n = 7 each). Injection of IP3 or CaCl2 increased the hSERT currents by
approximately 65% (P < 0.05; n = 10 each) and the effect of IP3 was abolished by
preinjection of EGTA. 4. These results demonstrate that hSERT activity is not
only voltage dependent, but is also affected by intracellular calcium and
extracellular sodium and chloride.
PMID- 17042921
TI - L-glutamate and glutamine improve haemodynamic function and restore myocardial
glycogen content during postischaemic reperfusion: A radioactive tracer study in
the rat isolated heart.
AB - 1. L-Glutamate and glutamine have been suggested to have cardioprotective
effects. However, the issue is controversial and the metabolic mechanisms
underlying a beneficial effect are not well understood. 2. In the present study
we investigated the effects of L-glutamate and glutamine on haemodynamic
recovery, the rate of de novo glycogen synthesis and myocardial glucose uptake
during postischaemic reperfusion. 3. Hearts from male Wistar rats (250-300 g)
were divided into three groups as follows: (i) control (n = 12); (ii) L-glutamate
(n = 12); and (iii) glutamine (n = 12). Hearts were mounted in a Langendorff
preparation and perfused with oxygenated Krebs'-Henseleit solution at 80 mmHg and
37C. Global ischaemia for 20 min was followed by 15 min reperfusion, during which
L-glutamate (50 mmol/L) or glutamine (20 mmol/L) were administered. Left
ventricular developed pressure (LVDP), de novo synthesis of glycogen using [14C]
glucose and myocardial glucose uptake using D-[2-3H]-glucose were measured. 4. L
Glutamate and glutamine increased postischaemic LVDP (P < 0.01 vs control hearts
for both). L-Glutamate and glutamine increased de novo glycogen synthesis by 78%
(P < 0.001) and 55% (P < 0.01), respectively. At the end of reperfusion, total
myocardial glycogen content was increased by both L-glutamate and glutamine (5.7
+/- 0.3 and 6.2 +/- 0.7 micromol/g wet weight, respectively; P < 0.05 and 0.01,
respectively) compared with that in control hearts (3.6 +/- 0.4 micromol/g wet
weight). Neither L-glutamate nor glutamine affected myocardial glucose uptake
during reperfusion. 5. Improved postischaemic haemodynamic recovery after L
glutamate and glutamine supplementation during reperfusion is associated with
increased de novo glycogen synthesis, suggesting a favourable modulation of
intracellular myocardial carbohydrate metabolism.
PMID- 17042920
TI - Effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine
pharmacokinetics after renal transplantation.
AB - 1. The calcineurin inhibitor cyclosporine is widely used to prevent allograft
rejection after solid organ transplantation. It has a narrow therapeutic index
and shows considerable interindividual differences in its pharmacokinetics.
Interindividual differences in the activity and expression of the metabolising
enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P
glycoprotein (P-gp) contribute considerably to cyclosporine pharmacokinetics.
Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to
result from genetic polymorphisms encoding their genes. 2. The aim of the present
study was to evaluate retrospectively the effects of genetic polymorphisms of
CYP3A4, CYP3A5 and MDR1 on cyclosporine dose adjusted trough blood concentration
during the early period after renal transplantation in Chinese patients. 3. One
hundred and six renal transplant recipients in China were genotyped by polymerase
chain reaction-restriction fragment length polymorphism for CYP3A4*18A, CYP3A5*3
and MDR1 C3435T. Cyclosporine whole blood levels were measured by fluorescence
polarization immunoassay. Dose-adjusted trough blood concentrations (C(0)) were
determined and compared among the different genotype groups. 4. The frequency of
the CYP3A4*18A, CYP3A5*3 and MDR1 C3435T variant alleles were 0.005 (95%
confidence interval (CI) 0.048, 0.0049), 0.783 (95% CI 0.781, 0.785) and 0.528
(95% CI 0.526, 0.531), respectively, and these alleles exhibited incomplete
linkage disequilibrium. The median cyclosporine dose-adjusted C(0) in CYP3A5*1/*1
genotype subjects (n = 6) was 14.8 ng/mL per mg per kg (range 11.1-26.8 ng/mL per
mg per kg), in CYP3A5*1/*3 patients (n = 34) it was 23.7 ng/mL per mg per kg
(range 9.0-61.0 ng/mL per mg per kg) and for CYP3A5*3/*3 patients (n = 66) it was
26.4 ng/mL per mg per kg (range 9.8-85.8 ng/mL per mg per kg; P = 0.012, Kruskal
Wallis test). Accordingly, cyclosporine dose-adjusted C0 was larger in CYP3A5 non
expressors than expressors in the first week after renal transplantation. In
addition, wild-type homozygotes (n = 21) for MDR1 C3435T had a slight but
significantly lower dose-adjusted C0 compared with heterozygotes (n = 58): 17.7
(10.3-60.8) versus 26.4 (9.0-67.3) ng/mL per mg per kg, respectively (P = 0.014,
Mann-Whitney U-test). 5. In conclusion, the present study shows that genetic
polymorphisms in CYP3A5 may be responsible, in part, for the large
interindividual variability of cyclosporine pharmacokinetics during the early
phase after renal transplantation in Chinese patients. Patients with the CYP3A5*3
variant genotype require a low dose of cyclosporine to reach target levels
compared with those with the CYP3A5*1 allele.
PMID- 17042922
TI - Antihyperglycaemic and antiperoxidative roles of acarbose in type 2 diabetes
mellitus are possibly mediated through changes in thyroid function.
AB - 1. The aim of the present study was to reveal the possible involvement of thyroid
hormones in the antihyperglycaemic and antiperoxidative effects of acarbose. 2.
The effects of acarbose on changes in serum concentration of thyroid hormones,
insulin and glucose in dexamethasone-induced type 2 diabetic mice were
investigated. Simultaneously, changes in lipid peroxidation (LPO), reduced
glutathione (GSH) content and the activity of associated endogenous anti-oxidant
enzymes, such as superoxide dismuatase (SOD) and catalase (CAT), were
investigated in renal and cardiac tissues, which are commonly affected in
diabetes mellitus. 3. Although administration of dexamethasone (1.0 mg/kg, i.m.,
for 22 days) caused hyperglycaemia with a parallel increase in serum insulin and
tissue LPO, it decreased thyroid hormone concentrations and the activity of SOD
and CAT. 4. When dexamethasone-induced hyperglycaemic mice were treated with
acarbose (10 mg/kg per day, p.o., for 15 days), levels of thyroid hormones were
increased and most of the abnormalities, including serum insulin and glucose
levels, tissue LPO, SOD and CAT activity and GSH content, were reversed. 5. These
findings suggest the involvement of thyroid hormones in the mode of action of
acarbose in amelioration of type 2 diabetes mellitus.
PMID- 17042923
TI - Regulation of ryanodine receptors from skeletal and cardiac muscle during rest
and excitation.
AB - 1. In muscle, intracellular calcium concentration, hence skeletal muscle force
and cardiac output, is regulated by uptake and release of calcium from the
sarcoplasmic reticulum (SR). The ryanodine receptor (RyR) forms the calcium
release channel in the SR. 2. Calcium release through RyRs is modulated by a wide
variety of endogenous molecules, including small diffusible ligands such as ATP,
Ca2+ and Mg2+. The regulation of RyR channels by ATP, Ca2+ and Mg2+ is a complex
interplay of several regulatory mechanisms, which are still being unravelled.
Consequently, it is not clearly known how RyRs are regulated in resting muscle
and during contraction. 3. The present paper reviews factors controlling the
activity of RyRs in skeletal and cardiac muscle with an emphasis on mechanistic
insights derived from single channel recording methods. 4. In addition, the
nature of dihydropyridine receptor (DHPR) control of RyRs in skeletal muscle
derived from experiments with peptide fragments of the DHPR II-III loop is
reviewed. 5. Finally, recent experiments on coupled RyRs in lipid bilayers and
their potential for resolving the elusive mechanisms controlling calcium release
during cardiac contraction are discussed.
PMID- 17042924
TI - Structural and functional characterization of interactions between the
dihydropyridine receptor II-III loop and the ryanodine receptor.
AB - 1. Excitation-contraction coupling in skeletal muscle is dependent on a physical
interaction between the dihydropyridine receptor (DHPR) and the ryanodine
receptor (RyR). 2. A number of peptides derived from the II-III loop region of
the DHPR have been shown to be functionally active in stimulating the release of
calcium via RyR channels. Their function has been found to correlate with the
presence of a basic helical region located at the N-terminus of the II-III loop.
3. The entire recombinant skeletal DHPR II-III loop is an efficient activator of
RyR1 and RyR2. 4. The skeletal DHPR II-III loop is comprised of a series of a
helices, but its tertiary structure has been determined to be unstructured and
flexible. 5. Fluorescence quenching experiments have been used to identify and
measure the binding affinity of the II-III loop with fragments of the RyR.
PMID- 17042925
TI - ClC-1 chloride channel: Matching its properties to a role in skeletal muscle.
AB - 1. ClC-1 is a Cl- channel in mammalian skeletal muscle that plays an important
role in membrane repolarization following muscular contraction. Reduction of ClC
1 conductance results in myotonia, a state characterized by muscle
hyperexcitability. 2. As is the case for other members of the ClC family, ClC-1
exists as a dimer that forms a double-barrelled channel. Each barrel, or pore, of
ClC-1 is gated by its own gate ('fast' or 'single pore' gate), whereas both pores
are gated simultaneously by another mechanism ('slow' or 'common' gate). 3.
Comparison of the biophysical and pharmacological properties of heterologously
expressed ClC-1 with the properties of the Cl- conductance measured in skeletal
muscle strongly suggests that ClC-1 is the major Cl- channel responsible for
muscle repolarization. However, not all results obtained in experiments on whole
muscle or muscle fibres support this notion. 4. In the present review we attempt
to bring together the current knowledge of ClC-1 with the physiology of skeletal
muscle.
PMID- 17042926
TI - Immune deficiencies and parasitic diseases.
PMID- 17042928
TI - Primary immunodeficiencies and susceptibility to parasitic infections.
AB - Primary immunodeficiencies are important disorders because they typically cause
severe illness in affected patients. In addition, these diseases provide a unique
glimpse at the underpinnings of the immune system in humans. Susceptibility to
infections, including those caused by parasites, is a hallmark of these immune
defects. Understanding the association between primary immunodeficiencies and
parasitic infections will likely improve our grasp on the mechanisms of defense
against these pathogens.
PMID- 17042930
TI - Co-infection of malaria with HIV: an immunological perspective.
AB - Human immunodeficiency virus (HIV) and Plasmodium parasites are pathogens that
induce significant perturbation and activation of the immune system. Due to their
geographical overlap, there have been concerns that co-infection with the two
pathogens may be a factor in the modification of their development, and in the
severity and rate of disease progression that they induce. In this article, we
have reviewed some of the studies that have addressed this topic and we have
tried to provide immunological mechanisms to explain these potential
interactions.
PMID- 17042929
TI - Interactions of malnutrition and immune impairment, with specific reference to
immunity against parasites.
AB - 1. Clinical malnutrition is a heterogenous group of disorders including
macronutrient deficiencies leading to body cell mass depletion and micronutrient
deficiencies, and these often coexist with infectious and inflammatory processes
and environmental problems. 2. There is good evidence that specific
micronutrients influence immunity, particularly zinc and vitamin A. Iron may have
both beneficial and deleterious effects depending on circumstances. 3. There is
surprisingly slender good evidence that immunity to parasites is dependent on
macronutrient intake or body composition.
PMID- 17042931
TI - Interactions between schistosomiasis and infection with HIV-1.
AB - In many regions of the world, both schistosomiasis and HIV/AIDS are endemic,
resulting in patients harbouring co-infections. Because interaction with host
CD4(+) T cells is a characteristic of schistosome as well as HIV-1 infections, bi
directional disease effects may be sufficiently different from sequelae caused by
either infectious agent alone to warrant alteration of public health approaches
in areas of co-endemnicity. Studies published over the past decade provide useful
insights into interactions between schistosomiasis and infection with HIV-1, and
overall support the hypothesis that special emphasis on treatment of
schistosomiasis in populations with elevated prevalence or risk of HIV-1
infection is justified.
PMID- 17042927
TI - The immunology of parasite infections in immunocompromised hosts.
AB - Immune compromise can modify the severity and manifestation of some parasitic
infections. More widespread use of newer immnosuppressive therapies, the growing
population of individuals with immunocompromised states as well as the prolonged
survival of these patients have altered the pattern of parasitic infection. This
review article discusses the burden and immunology of parasitic infections in
patients who are immunocompromised secondary to congenital immunodeficiency,
malnutrition, malignancy, and immunosuppressive medications. This review does not
address the literature on parasitic infections in the setting of HIV-1 infection.
PMID- 17042932
TI - HIV and helminth co-infection: is deworming necessary?
AB - We have previously suggested that helminth infections play a major role in the
pathogenesis of HIV-1 infection in Africa and other developing areas, due to
their profound effects on the host immune system, which make those infected more
susceptible to HIV-1 infection and less able to cope with it. Chronic immune
activation with a dominant Th2 profile, and anergy, are the hallmarks of chronic
helminth infection, and may therefore account for most of these effects. In the
present review, we summarize the studies that have addressed these issues and
argue that despite some conflicting results, the cumulative immunological and
epidemiological evidence is in favour of deworming as a preventive and possible
therapeutic measure vis-a-vis HIV-1 infection. We suggest that it should be at
least tested on a wider and larger scale than has been done until now, because of
its immense potential impact on the still raging AIDS epidemic in developing
countries.
PMID- 17042933
TI - Helminths and HIV infection: epidemiological observations on immunological
hypotheses.
AB - Parasitic helminths have co-evolved with the mammalian immune system. Current
hypotheses suggest that immunological stimulation in the presence of helminths is
balanced by immuno-regulation and by the broad spectrum of mechanisms possessed
by helminths for countering the host immune response. The degree to which this
balance is perfected, and the mechanisms by which this is achieved, vary between
helminth species; we suggest that this is reflected not only in the degree of
pathology induced by helminths but also in a variety of relationships with HIV
infection and HIV disease. Available epidemiological data regarding interactions
between helminths and HIV are largely observational; results are variable and
generally inconclusive. Well designed, controlled intervention studies are
required to provide definitive information on the species-specific nature of
these interactions and on the advantages, disadvantages and optimal timing of de
worming in relation to HIV infection.
PMID- 17042935
TI - REEF: searching REgionally Enriched Features in genomes.
AB - BACKGROUND: In Eukaryotic genomes, different features including genes are not
uniformly distributed. The integration of annotation information and genomic
position of functional DNA elements in the Eukaryotic genomes opened the way to
test novel hypotheses of higher order genome organization and regulation of
expression. RESULTS: REEF is a new tool, aimed at identifying genomic regions
enriched in specific features, such as a class or group of genes homogeneous for
expression and/or functional characteristics. The method for the calculation of
local feature enrichment uses test statistic based on the Hypergeometric
Distribution applied genome-wide by using a sliding window approach and adopting
the False Discovery Rate for controlling multiplicity. REEF software, source code
and documentation are freely available at
http://telethon.bio.unipd.it/bioinfo/reef/. CONCLUSION: REEF can aid to shed
light on the role of organization of specific genomic regions in the
determination of their functional role.
PMID- 17042936
TI - Comparison of capillary based microflurometric assay for CD4+ T cell count
estimation with dual platform Flow cytometry.
AB - The CD4+ T cell count estimation is an important monitoring tool for HIV disease
progression and efficacy of anti-retroviral treatment (ART). Due to availability
of ART at low cost in developing countries, quest for reliable cost effective
alternative methods for CD4+ T cell count estimation has gained importance. A
simple capillary-based microflurometric assay (EasyCD4 System, Guava Technology)
was compared with the conventional flow cytometric assay for estimation of CD4+ T
cell counts in 79 HIV infected individuals. CD4+ T cell count estimation by both
the assays showed strong correlation (r = 0.938, p < 0.001, 95% CI 0.90 to 0.96).
The Bland Altman plot analysis showed that the limits of variation were within
agreeable limits of +/- 2SD (-161 to 129 cells/mm3). The Easy CD4 assay showed
100% sensitivity for estimating the CD4+ T cell counts < 200 cells/mm3 and < 350
cells/mm3 and 97% sensitivity to estimate CD4+ T cell count < 500 cells/mm3. The
specificity ranged from 82 to 100%. The Kappa factor ranged from 0.735 for the
CD4+ T cell counts < 350 cells/mm3 to 0.771 for < 500 cells/mm3 CD4+ T cell
counts. The system works with a simple protocol, is easy to maintain and has low
running cost. The system is compact and generates minimum amount of waste. Hence
the EasyCD4 System could be applied for estimation of CD4+ T cell counts in
resource poor settings.
PMID- 17042934
TI - Immune reconstitution disease associated with parasitic infections following
antiretroviral treatment.
AB - HIV-associated immune reconstitution disease (IRD) is the clinical presentation
or deterioration of opportunistic infections that results from enhancement of
pathogen-specific immune responses among patients responding to antiretroviral
treatment (ART). The vast majority of reported cases of IRD have been associated
with mycobacterial, chronic viral and invasive fungal infections; such cases
result from dysregulated augmentation of cell-mediated type 1 cytokine-secreting
host immune responses. However, the spectrum of infections now recognized as
associated with IRD is expanding and includes a number of parasitic infections,
which may be mediated by different immunopathological mechanisms. These include
leishmaniasis (visceral, cutaneous, mucosal and post kala azar dermal
leishmaniasis), schistosomiasis and strongyloidiasis. Since the major burden of
HIV lies in resource-limited countries where access to ART is now rapidly
expanding, increased awareness and knowledge of these phenomena is important.
Here we review the clinical spectrum and pathogenesis of IRD associated with
parasitic infections.
PMID- 17042937
TI - Atlanto-axial rotatory fixation in a girl with Spondylocarpotarsal synostosis
syndrome.
AB - We report a 15-year-old girl who presented with spinal malsegmentation,
associated with other skeletal anomalies. The spinal malsegmentation was
subsequently discovered to be part of the spondylocarpotarsal synostosis
syndrome. In addition, a distinctive craniocervical malformation was identified,
which included atlanto-axial rotatory fixation. The clinical and the radiographic
findings are described, and we emphasise the importance of computerised
tomography to characterize the craniocervical malformation complex. To the best
of our knowledge, this is the first clinical report of a child with
spondylocarpotarsal synostosis associated with atlanto-axial rotatory fixation.
PMID- 17042938
TI - Alternative technologies in cervical cancer screening: a randomised evaluation
trial.
AB - BACKGROUND: Cervical cancer screening programmes have markedly reduced the
incidence and mortality rates of the disease. A substantial amount of deaths from
the disease could be prevented further by organised screening programmes or
improving currently running programmes. METHODS/DESIGN: We present here a
randomised evaluation trial design integrated to the Finnish cervical cancer
screening programme, in order to evaluate renewal of the programme using emerging
technological alternatives. The main aim of the evaluation is to assess screening
effectiveness, using subsequent cancers as the outcome and screen-detected pre
cancers as surrogates. For the time being, approximately 863,000 women have been
allocated to automation-assisted cytology, human papillomavirus (HPV) DNA
testing, or to conventional cytology within the organised screening programme.
Follow-up results on subsequent cervical cancers will become available during
2007-2015. DISCUSSION: Large-scale randomised trials are useful to clarify
effectiveness and cost-effectiveness issues of the most important technological
alternatives in the screening programmes for cervical cancer.
PMID- 17042939
TI - Time- and concentration-dependent changes in gene expression induced by
benzo(a)pyrene in two human cell lines, MCF-7 and HepG2.
AB - BACKGROUND: The multi-step process of carcinogenesis can be more fully understood
by characterizing gene expression changes induced in cells by carcinogens. In
this study, expression microarrays were used to monitor the activity of 18,224
cDNA clones in MCF-7 and HepG2 cells exposed to the carcinogen benzo(a)pyrene
(BaP) or its non-carcinogenic isomer benzo(e)pyrene (BeP). Time and concentration
gene expression effects of BaP exposure have been assessed and linked to other
measures of cellular stress to aid in the identification of novel genes/pathways
involved in the cellular response to genotoxic carcinogens. RESULTS: BaP (0.25
5.0 muM; 6-48 h exposure) modulated 202 clones in MCF-7 cells and 127 in HepG2
cells, including 27 that were altered in both. In contrast, BeP did not induce
consistent gene expression changes at the same concentrations. Significant time-
and concentration-dependent responses to BaP were seen in both cell lines.
Expression changes observed in both cell lines included genes involved in
xenobiotic metabolism (e.g., CYP1B1, NQO1, MGST1, AKR1C1, AKR1C3,CPM), cell cycle
regulation (e.g., CDKN1A), apoptosis/anti-apoptosis (e.g., BAX, IER3), chromatin
assembly (e.g., histone genes), and oxidative stress response (e.g., TXNRD1).
RTqPCR was used to validate microarray data. Phenotypic anchoring of the
expression data to DNA adduct levels detected by 32P-postlabelling, cell cycle
data and p53 protein expression identified a number of genes that are linked to
these biological outcomes, thereby strengthening the identification of target
genes. The overall response to BaP consisted of up-regulation of tumour
suppressor genes and down-regulation of oncogenes promoting cell cycle arrest and
apoptosis. Anti-apoptotic signalling that may increase cell survival and promote
tumourigenesis was also evident. CONCLUSION: This study has further characterised
the gene expression response of human cells after genotoxic insult, induced after
exposure to concentrations of BaP that result in minimal cytotoxicity. We have
demonstrated that investigating the time and concentration effect of a carcinogen
on gene expression related to other biological end-points gives greater insight
into cellular responses to such compounds and strengthens the identification of
target genes.
PMID- 17042940
TI - Severe malnutrition with and without HIV-1 infection in hospitalised children in
Kampala, Uganda: differences in clinical features, haematological findings and
CD4+ cell counts.
AB - BACKGROUND: The aim of this study was to describe the clinical features,
haematological findings and CD4+ and CD8+ cell counts of severely malnourished
children in relation to human immunodeficiency virus (HIV) infection. METHODS:
The study was conducted in the paediatric wards of Mulago hospital, which is
Uganda's national referral and teaching hospital. We studied 315 severely
malnourished children (presence of oedema and/or weight-for-height: z-score < -3)
and have presented our findings. At admission, the CD4+ and CD8+ cells were
measured by the flow cytometry and HIV serology was confirmed by Enzyme linked
Immunoassay for children >18 months of age, and RNA PCR was performed for those <
or =18 months. Complete blood count, including differential counts, was
determined using a Beckman Coulter counter. RESULTS: Among the 315 children, 119
(38%) were female; the median age of these children was 17 months (Interquartile
range 12-24 months), and no difference was observed in the HIV status with regard
to gender or age. The children showed a high prevalence of infections: pneumonia
(68%), diarrhoea (38%), urinary tract infection (26%) and bacteraemia (18%), with
no significant difference with regard to the HIV status (HIV-positive versus HIV
negative children). However, the HIV-positive children were more likely to have
persistent diarrhoea than the HIV-uninfected severely malnourished children (odds
ratio (OR) 2.0, 95% confidence interval (CI) 1.2-3.6). When compared with the HIV
negative children, the HIV-positive children showed a significantly lower median
white blood cell count (10700 versus 8700) and lymphocyte count (4033 versus
2687). The CD4+ cell percentages were more likely to be lower in children with
non-oedematous malnutrition than in those with oedematous malnutrition even after
controlling for the HIV infection. The novel observation of this study is that
the CD4+ percentages in both HIV-positive and HIV-negative children without
oedema were lower that those in children with oedema. These observations appear
to imply that the development of oedema requires a certain degree of
immunocompetence, which is an interesting clue to the pathophysiology of oedema
in severe malnutrition.
PMID- 17042942
TI - Whole genome association mapping by incompatibilities and local perfect
phylogenies.
AB - BACKGROUND: With current technology, vast amounts of data can be cheaply and
efficiently produced in association studies, and to prevent data analysis to
become the bottleneck of studies, fast and efficient analysis methods that scale
to such data set sizes must be developed. RESULTS: We present a fast method for
accurate localisation of disease causing variants in high density case-control
association mapping experiments with large numbers of cases and controls. The
method searches for significant clustering of case chromosomes in the "perfect"
phylogenetic tree defined by the largest region around each marker that is
compatible with a single phylogenetic tree. This perfect phylogenetic tree is
treated as a decision tree for determining disease status, and scored by its
accuracy as a decision tree. The rationale for this is that the perfect phylogeny
near a disease affecting mutation should provide more information about the
affected/unaffected classification than random trees. If regions of compatibility
contain few markers, due to e.g. large marker spacing, the algorithm can allow
the inclusion of incompatibility markers in order to enlarge the regions prior to
estimating their phylogeny. Haplotype data and phased genotype data can be
analysed. The power and efficiency of the method is investigated on 1) simulated
genotype data under different models of disease determination 2) artificial data
sets created from the HapMap ressource, and 3) data sets used for testing of
other methods in order to compare with these. Our method has the same accuracy as
single marker association (SMA) in the simplest case of a single disease causing
mutation and a constant recombination rate. However, when it comes to more
complex scenarios of mutation heterogeneity and more complex haplotype structure
such as found in the HapMap data our method outperforms SMA as well as other
fast, data mining approaches such as HapMiner and Haplotype Pattern Mining (HPM)
despite being significantly faster. For unphased genotype data, an initial step
of estimating the phase only slightly decreases the power of the method. The
method was also found to accurately localise the known susceptibility variants in
an empirical data set--the DeltaF508 mutation for cystic fibrosis--where the
susceptibility variant is already known--and to find significant signals for
association between the CYP2D6 gene and poor drug metabolism, although for this
dataset the highest association score is about 60 kb from the CYP2D6 gene.
CONCLUSION: Our method has been implemented in the Blossoc (BLOck aSSOCiation)
software. Using Blossoc, genome wide chip-based surveys of 3 million SNPs in 1000
cases and 1000 controls can be analysed in less than two CPU hours.
PMID- 17042941
TI - Stroke prevalence among the Spanish elderly: an analysis based on screening
surveys.
AB - BACKGROUND: This study sought to describe stroke prevalence in Spanish elderly
populations and compare it against that of other European countries. METHODS: We
identified screening surveys--both published and unpublished--in Spanish
populations, which fulfilled specific quality requirements and targeted
prevalence of stroke in populations aged 70 years and over. Surveys covering
seven geographically different populations with prevalence years in the period
1991-2002 were selected, and the respective authors were then asked to provide
descriptions of the methodology and raw age-specific data by completing a
questionnaire. In addition, five reported screening surveys in European
populations furnished useful data for comparison purposes. Prevalence data were
combined, using direct adjustment and logistic regression. RESULTS: The overall
study population, resident in central and north-eastern Spain, totalled 10,647
persons and yielded 715 cases. Age-adjusted prevalences, using the European
standard population, were 7.3% for men, 5.6% for women, and 6.4% for both sexes.
Prevalence was significantly lower in women, OR 0.79 95% CI 0.68-0.93, increased
with age, particularly among women, and displayed a threefold spatial variation
with statistically significant differences. Prevalences were highest, 8.7%, in
suburban, and lowest, 3.8%, in rural populations. Compared to pooled Spanish
populations, statistically significant differences were seen in eight Italian
populations, OR 1.39 95% CI (1.18-1.64), and in Kungsholmen, Sweden, OR 0.40 95%
CI (0.27-0.58). CONCLUSION: Prevalence in central and north-eastern Spain is
higher in males and in suburban areas, and displays a threefold geographic
variation, with women constituting the majority of elderly stroke sufferers.
Compared to reported European data, stroke prevalence in Spain can be said to be
medium and presents similar age- and sex-specific traits.
PMID- 17042943
TI - Building multiclass classifiers for remote homology detection and fold
recognition.
AB - BACKGROUND: Protein remote homology detection and fold recognition are central
problems in computational biology. Supervised learning algorithms based on
support vector machines are currently one of the most effective methods for
solving these problems. These methods are primarily used to solve binary
classification problems and they have not been extensively used to solve the more
general multiclass remote homology prediction and fold recognition problems.
RESULTS: We present a comprehensive evaluation of a number of methods for
building SVM-based multiclass classification schemes in the context of the SCOP
protein classification. These methods include schemes that directly build an SVM
based multiclass model, schemes that employ a second-level learning approach to
combine the predictions generated by a set of binary SVM-based classifiers, and
schemes that build and combine binary classifiers for various levels of the SCOP
hierarchy beyond those defining the target classes. CONCLUSION: Analyzing the
performance achieved by the different approaches on four different datasets we
show that most of the proposed multiclass SVM-based classification approaches are
quite effective in solving the remote homology prediction and fold recognition
problems and that the schemes that use predictions from binary models constructed
for ancestral categories within the SCOP hierarchy tend to not only lead to lower
error rates but also reduce the number of errors in which a superfamily is
assigned to an entirely different fold and a fold is predicted as being from a
different SCOP class. Our results also show that the limited size of the training
data makes it hard to learn complex second-level models, and that models of
moderate complexity lead to consistently better results.
PMID- 17042945
TI - C-reactive protein in aortic valve disease.
AB - Aortic Valve Disease, includes a range of disorder severity from mild leaflet
thickening without valve obstruction, "aortic sclerosis", to severe calcified
aortic stenosis. It is a slowly progressive active process of valve modification
similar atherosclerosis for cardiovascular risk factors, lipoprotein deposition,
chronic inflammation, and calcification. Systemic signs of inflammation, as wall
and serum CRP, similar to those found in atherosclerosis, are present in patients
with degenerative aortic valve stenosis and may be expression of a common
disease, useful in monitoring of stenosis progression.
PMID- 17042944
TI - The eggshell is required for meiotic fidelity, polar-body extrusion and
polarization of the C. elegans embryo.
AB - BACKGROUND: Fertilization restores the diploid state and begins the process by
which the single-cell oocyte is converted into a polarized, multicellular
organism. In the nematode, Caenorhabditis elegans, two of the earliest events
following fertilization are secretion of the chitinous eggshell and completion of
meiosis, and in this report we demonstrate that the eggshell is essential for
multiple developmental events at the one-cell stage. RESULTS: We show that the
GLD (Germline differentiation abnormal)-1-regulated hexosamine pathway enzyme,
glucosamine-6-phosphate N-acetyltransferase (GNA)-2, is required for synthesis of
uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc), the substrate for eggshell
chitin synthesis by chitin synthase-1 (CHS-1). Furthermore, while chs-1(RNAi) or
combined RNAi with the chitin-binding proteins, CEJ-1 and B0280.5, does not
interfere with normal meiotic timing, lagging chromosomes are observed at
meiosis, and polar-body extrusion fails. We also demonstrate that chitin, and
either CEJ-1 or B0280.5, are essential for the osmotic/permeability barrier and
for movement of the sperm pronucleus/centrosome complex to the cortex, which is
associated with the initiation of polarization. CONCLUSION: Our results indicate
that the eggshell is required in single-cell C. elegans development, playing an
essential role in multiple actin-dependent early events. Furthermore, the
earliest meiotic roles precede osmotic barrier formation, indicating that the
role of the eggshell is not limited to generation of the osmotic barrier.
PMID- 17042946
TI - Levels of acute phase proteins remain stable after ischemic stroke.
AB - BACKGROUND: Inflammation and inflammatory biomarkers play an important role in
atherosclerosis and cardiovascular disease. Little information is available,
however, on time course of serum markers of inflammation after stroke. METHODS:
First ischemic stroke patients > or =40 years old had levels of high-sensitivity
C-reactive protein (hsCRP), serum amyloid A (SAA), and fibrinogen measured in
plasma samples drawn at 1, 2, 3, 7, 14, 21 and 28 days after stroke. Levels were
log-transformed as needed, and parametric and non-parametric statistical tests
were used to test for evidence of a trend in levels over time. Levels of hsCRP
and SAA were also compared with levels in a comparable population of stroke-free
participants. RESULTS: Mean age of participants with repeated measures (n = 21)
was 65.6 +/- 11.6 years, and 13 (61.9%) were men, and 15 (71.4%) were Hispanic.
Approximately 75% of patients (n = 15) had mild strokes (NIH Stroke Scale score 0
5). There was no evidence of a time trend in levels of hsCRP, SAA, or fibrinogen
for any of the markers during the 28 days of follow-up. Mean log(hsCRP) was 1.67
+/- 1.07 mg/L (median hsCRP 6.48 mg/L) among stroke participants and 1.00 +/-
1.18 mg/L (median 2.82 mg/L) in a group of 1176 randomly selected stroke-free
participants from the same community (p = 0.0252). CONCLUSION: Levels of hsCRP
are higher in stroke patients than in stroke-free subjects. Levels of
inflammatory biomarkers associated with atherosclerosis, including hsCRP, appear
to be stable for at least 28 days after first ischemic stroke.
PMID- 17042947
TI - Cloning, expression and functional activity of deoxyhypusine synthase from
Plasmodium vivax.
AB - BACKGROUND: Plasmodium vivax is the most widespread human malaria parasite.
However, genetic information about its pathogenesis is limited at present, due to
the lack of a reproducible in vitro cultivation method. Sequencing of the
Plasmodium vivax genome suggested the presence of a homolog of deoxyhypusine
synthase (DHS) from P. falciparum, the key regulatory enzyme in the first
committed step of hypusine biosynthesis. DHS is involved in cell proliferation,
and thus a valuable drug target for the human malaria parasite P. falciparum. A
comparison of the enzymatic properties of the DHS enzymes between the benign and
severe Plasmodium species should contribute to our understanding of the
differences in pathogenicity and phylogeny of both malaria parasites. RESULTS: We
describe the cloning of a 1368 bp putative deoxyhypusine synthase gene (dhs)
sequence from genomic DNA of P. vivax PEST strain Salvador I (Accession number
AJ549098) after touchdown PCR. The corresponding protein was expressed and
functionally characterized as deoxyhypusine synthase by determination of its
specific activity and cross-reactivity to human DHS on a Western blot. The
putative DHS protein from P. vivax displays a FASTA score of 75 relative to DHS
from rodent malaria parasite, P. yoelii, and 74 relative to that from the human
parasite, P. falciparum strain 3D7. The ORF encoding 456 amino acids was
expressed under control of IPTG-inducible T7 promoter, and expressed as a protein
of approximately 50 kDa (theoretically 52.7 kDa) in E. coli BL21 DE3 cells. The N
terminal histidine-tagged protein was purified by Nickel-chelate affinity
chromatography under denaturing conditions. DHS with a theoretical pI of 6.0 was
present in both eluate fractions. The specific enzymatic activity of DHS was
determined as 1268 U/mg protein. The inhibitor, N-guanyl-1, 7-diaminoheptane
(GC7), suppressed specific activity by 36-fold. Western blot analysis performed
with a polyclonal anti-human DHS antibody revealed cross-reactivity to DHS from
P. vivax, despite an amino acid identity of 44% between the proteins. CONCLUSION:
We identify a novel DHS protein in the more benign malaria parasite,P. vivax, on
the basis of specific enzymatic activity, cross-reactivity with a polyclonal
antibody against human DHS, and amino acid identity with DHS homologs from the
rodent malaria parasite, P. yoelii, and human P. falciparum strains.
PMID- 17042948
TI - Evaluation of three 3ABC ELISAs for foot-and-mouth disease non-structural
antibodies using latent class analysis.
AB - BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious viral disease of
even-toed ungulates. Serological diagnosis/surveillance of FMD presents several
problems as there are seven serotypes worldwide and in the event of vaccination
it may be necessary to be able to identify FMD infected/exposed animals
irrespective of their vaccination status. The recent development of non
structural 3ABC protein (NSP) ELISA tests has greatly advanced sero
diagnosis/surveillance as these tests detect exposure to live virus for any of
the seven serotypes of FMD, even in vaccinated populations. This paper analyses
the performance of three NSP tests using a Bayesian formulation of the Hui-Walter
latent class model to estimate test sensitivity and specificity in the absence of
a "gold-standard" test, using sera from a well described cattle population in
Cameroon with endemic FMD. RESULTS: The analysis found a high sensitivity and
specificity for both the Danish C-ELISA and the World Organisation for Animal
Health (O.I.E.) recommended South American I-ELISA. However, the commercial
CHEKIT kit, though having high specificity, has very low sensitivity. The results
of the study suggests that for NSP ELISAs, latent class models are a useful
alternative to the traditional approach of evaluating diagnostic tests against a
known "gold-standard" test as imperfections in the "gold-standard" may give
biased test characteristics. CONCLUSION: This study demonstrates that when
applied to naturally infected zebu cattle managed under extensive rangeland
conditions, the FMD ELISAs may not give the same parameter estimates as those
generated from experimental studies. The Bayesian approach allows for full
posterior probabilities and capture of the uncertainty in the estimates. The
implications of an imperfect specificity are important for the design and
interpretation of sero-surveillance data and may result in excessive numbers of
false positives in low prevalence situations unless a follow-up confirmatory test
such as the enzyme linked immunoelectrotransfer blot (EITB) is used.
PMID- 17042949
TI - Re-interpreting conventional interval estimates taking into account bias and
extra-variation.
AB - BACKGROUND: The study design with the smallest bias for causal inference is a
perfect randomized clinical trial. Since this design is often not feasible in
epidemiologic studies, an important challenge is to model bias properly and take
random and systematic variation properly into account. A value for a target
parameter might be said to be "incompatible" with the data (under the model used)
if the parameter's confidence interval excludes it. However, this
"incompatibility" may be due to bias and/or extra-variation. DISCUSSION: We
propose the following way of re-interpreting conventional results. Given a
specified focal value for a target parameter (typically the null value, but
possibly a non-null value like that representing a twofold risk), the difference
between the focal value and the nearest boundary of the confidence interval for
the parameter is calculated. This represents the maximum correction of the
interval boundary, for bias and extra-variation, that would still leave the focal
value outside the interval, so that the focal value remained "incompatible" with
the data. We describe a short example application concerning a meta analysis of
air versus pure oxygen resuscitation treatment in newborn infants. Some general
guidelines are provided for how to assess the probability that the appropriate
correction for a particular study would be greater than this maximum (e.g. using
knowledge of the general effects of bias and extra-variation from published bias
adjusted results). SUMMARY: Although this approach does not yet provide a method,
because the latter probability can not be objectively assessed, this paper aims
to stimulate the re-interpretation of conventional confidence intervals, and more
and better studies of the effects of different biases.
PMID- 17042950
TI - Anemia, costs and mortality in chronic obstructive pulmonary disease.
AB - BACKGROUND: Little is known about cost implications of anemia and its association
with mortality in chronic obstructive pulmonary disease (COPD). This claims
analysis addresses these questions. METHODS: Using the the US Medicare claims
database (1997-2001), this study identified Medicare enrollees with an ICD-9
diagnosis of COPD. Concomitant anemia was identified based on ICD-9 codes or
receipt of transfusions. Persons with anemia secondary to another disease state,
a nutritional deficiency or a hereditary disease were excluded. Medicare claims
and payments, resource utilization and mortality were compared between COPD
patients with and without anemia. RESULTS: Of the 132,424 enrollees with a COPD
diagnosis, 21% (n = 27,932) had concomitant anemia. At baseline, anemic patients
were older, had more co-morbidities and higher rates of health care resource use
than non-anemic individuals with COPD. In a univariate analysis annual Medicare
payments for persons with anemia were more than double for those without anemia
($1,466 vs. $649, p < 0.001), the direction maintained in all categories of
payments. Adjusting for demographics, co-morbidities, and other markers of
disease severity revealed that anemia was independently associated with $3,582
incremental increase per patient (95% CI: $3,299 to $3,865) in Medicare annual
reimbursements. The mortality rate among COPD patients with anemia was 262 vs.
133 deaths per 1,000 person-years among those without anemia (p < 0.001).
CONCLUSION: Anemia was present in 21% of COPD patients. Although more prevalent
in more severely ill COPD patients, anemia significantly and independently
contributes to the costs of care for COPD and is associated with increased
mortality.
PMID- 17042951
TI - Audit of the change in the on-call practices in neuroradiology and factors
affecting it.
AB - BACKGROUND: On call practices had recently changed at the Newcastle General
Hospital to accommodate increasing CT scan requests and reduce the workloads of
the radiologists. In the new system, the person responsible for dealing with the
out of hours requests for imaging changed from the neuroradiologist to the
neuroradiographer. This audit was conducted to assess any change in the
departmental workload as a result of this change. METHODS: The audit was carried
out over a period of six months and data was collected from the on-call booklets
which the neuroradiographers maintained and the log books maintained in the
department of neuroradiology. Details of the imaging requested; the source of the
request, the reason for the request and the results of the scans were recorded
and analysed using Microsoft Excel. RESULTS: The number of CT scans requested
from the A&E went up by 73.4% after the change in practice and majority of these
increases were due to increased requests for scans on head injuries which
increased by 122%. Although this was not statistically significant due to lack of
study power, it is clinically relevant. CONCLUSION: The increase in the number of
CT scans for head injuries reflects a general change in practice in management of
head injuries in the UK. Changing the gatekeeper from radiologist to radiographer
was associated with an increase in CT rate, particularly for head injuries. Other
factors such as clinician seniority and a greater awareness of the NICE
guidelines may have also contributed.
PMID- 17042952
TI - Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem
cells carrying allelic fluorescent protein genes.
AB - BACKGROUND: Loss of heterozygosity (LOH) contributes to many cancers, but the
rate at which these events occur in normal cells of the body is not clear. LOH
would be detectable in diverse cell types in the body if this event were to
confer an obvious cellular phenotype. Mice that carry two different fluorescent
protein genes as alleles of a locus would seem to be a useful tool for addressing
this issue because LOH would change a cell's phenotype from dichromatic to
monochromatic. In addition, LOH caused by mitotic crossing over might be
discernable in tissues because this event produces a pair of neighboring
monochromatic cells that are different colors. RESULTS: As a step in assessing
the utility of this approach, we derived primary embryonic fibroblast populations
and embryonic stem cell lines from mice that carried two different fluorescent
protein genes as alleles at the chromosome 6 locus, ROSA26. Fluorescence
activated cell sorting (FACS) showed that the vast majority of cells in each line
expressed the two marker proteins at similar levels, and that populations
exhibited expression noise similar to that seen in bacteria and yeast. Cells with
a monochromatic phenotype were present at frequencies on the order of 10(-4) and
appeared to be produced at a rate of approximately 10(-5) variant cells per
mitosis. 45 of 45 stably monochromatic ES cell clones exhibited loss of the
expected allele at the ROSA26 locus. More than half of these clones retained
heterozygosity at a locus between ROSA26 and the centromere. Other clones
exhibited LOH near the centromere, but were disomic for chromosome 6. CONCLUSION:
Allelic fluorescent markers allowed LOH at the ROSA26 locus to be detected by
FACS. LOH at this locus was usually not accompanied by LOH near the centromere,
suggesting that mitotic recombination was the major cause of ROSA26 LOH.
Dichromatic mouse embryonic cells provide a novel system for studying
genetic/karyotypic stability and factors influencing expression from allelic
genes. Similar approaches will allow these phenomena to be studied in tissues.
PMID- 17042953
TI - Atypically diffuse functional connectivity between caudate nuclei and cerebral
cortex in autism.
AB - BACKGROUND: Autism is a neurodevelopmental disorder affecting sociocommunicative
behavior, but also sensorimotor skill learning, oculomotor control, and executive
functioning. Some of these impairments may be related to abnormalities of the
caudate nuclei, which have been reported for autism. METHODS: Our sample was
comprised of 8 high-functioning males with autism and 8 handedness, sex, and age
matched controls. Subjects underwent functional MRI scanning during performance
on simple visuomotor coordination tasks. Functional connectivity MRI (fcMRI)
effects were identified as interregional blood oxygenation level dependent (BOLD)
signal cross-correlation, using the caudate nuclei as seed volumes. RESULTS: In
the control group, fcMRI effects were found in circuits with known participation
of the caudate nuclei (associative, orbitofrontal, oculomotor, motor circuits).
Although in the autism group fcMRI effects within these circuits were less
pronounced or absent, autistic subjects showed diffusely increased connectivity
mostly in pericentral regions, but also in brain areas outside expected
anatomical circuits (such as visual cortex). CONCLUSION: These atypical
connectivity patterns may be linked to developmental brain growth disturbances
recently reported in autism and suggest inefficiently organized functional
connectivity between caudate nuclei and cerebral cortex, potentially accounting
for stereotypic behaviors and executive impairments.
PMID- 17042954
TI - Novel insights on effect of atrioventricular programming of biventricular
pacemaker in heart failure--a case series.
AB - BACKGROUND: Echocardiography plays an integral role in the diagnosis of
congestive heart failure including measurement of left heart pressure as well as
mechanical dyssynchrony. METHODS: In this report we describe novel therapeutic
uses of echo pulsed wave Doppler in atrioventricular pacemaker optimization in
patients who had either not derived significant symptomatic benefit post
biventricular pacemaker implantation or deteriorated after deriving initial
benefit. In these patients atrioventricular optimization showed novel findings
and improved cardiac output and symptoms. RESULTS: In 3 patients with Cheyne
Stokes pattern of respiration echo Doppler showed worsening of mitral
regurgitation during hyperpneac phase in one patient, marked E and A fusion in
another patient and exaggerated ventricular interdependence in a third patient
thus highlighting mechanisms of adverse effects of Cheyne Stokes respiration in
patients with heart failure. All 3 patients required a very short
atrioventricular delay programming for best cardiac output. In one patient with
recurrent congestive heart failure post cardiac resynchronization, mitral inflow
pulse wave Doppler showed no A wave until a sensed atrioventricular delay of 190
ms was reached and showed progressive improvement in mitral inflow pattern until
an atrioventricular delay of 290 ms. In 2 patients atrioventricular delay as
short as 50 ms was required to allow E and A separation and prevent diastolic
mitral regurgitation. All patients developed marked improvement in congestive
heart failure symptoms post echo-guided biv pacemaker optimization. CONCLUSION:
These findings highlight the value of echo-guided pacemaker optimization in
symptomatic patients post cardiac resynchronization treatment.
PMID- 17042955
TI - Social support during intensive care unit stay might improve mental impairment
and consequently health-related quality of life in survivors of severe acute
respiratory distress syndrome.
AB - INTRODUCTION: We investigated health-related quality of life (HRQoL) and
persistent symptoms of post-traumatic stress disorder (PTSD) in long-term
survivors of acute respiratory distress syndrome (ARDS). We wished to evaluate
the influence of PTSD on HRQoL and to investigate the influence of perceived
social support during intensive care unit (ICU) treatment on both PTSD symptoms
and HRQoL. METHODS: In ARDS patients we prospectively measured HRQoL (Medical
Outcomes Study 36-Item Short Form; SF-36), symptoms of PTSD (Post-Traumatic
Stress Syndrome 10-Questions Inventory; PTSS-10), perceived social support
(Questionnaire for Social Support; F-Sozu) and symptoms of psychopathology
(Symptom Checklist-90-R); and collected sociodemographic data including current
employment status. Sixty-five (50.4%) out of 129 enrolled survivors responded, on
average 57 +/- 32 months after discharge from ICU. Measuring symptoms of PTSD the
PTSS-10 was used to divide the ARDS patients into two subgroups ('high-scoring
patients', indicating patients with an increased risk for developing PTSD, and
'low-scoring patients'). RESULTS: HRQoL was significantly reduced in all
dimensions in comparison with age- and gender-adjusted healthy controls. Eighteen
patients (29%) were identified as being at increased risk for PTSD. PTSD risk was
significantly linked with anxiety during their ICU stay. In this group of
patients there was a trend towards permanent or temporary disability, independent
of the period between discharge from ICU and study entry. Perceived social
support was associated with a reduction in PTSD symptoms (Pearson correlation; p
< 0.05). Post-hoc test revealed a significant difference between 'high-scoring
patients' and 'low-scoring patients' with respect to mental health, although they
did not differ in physical dimensions. CONCLUSION: HRQoL was reduced in long-term
survivors, and was linked with an increased risk of chronic PTSD with ensuing
psychological morbidity. This was independent of physical condition and was
associated with traumatic memories of anxiety during their ICU stay. Social
support might improve mental health and consequently long-term outcome including
employment status.
PMID- 17042956
TI - Alterations of metabolic activity in human osteoarthritic osteoblasts by lipid
peroxidation end product 4-hydroxynonenal.
AB - 4-Hydroxynonenal (HNE), a lipid peroxidation end product, is produced abundantly
in osteoarthritic (OA) articular tissues, but its role in bone metabolism is ill
defined. In this study, we tested the hypothesis that alterations in OA
osteoblast metabolism are attributed, in part, to increased levels of HNE. Our
data showed that HNE/protein adduct levels were higher in OA osteoblasts compared
to normal and when OA osteoblasts were treated with H2O2. Investigating
osteoblast markers, we found that HNE increased osteocalcin and type I collagen
synthesis but inhibited alkaline phosphatase activity. We next examined the
effects of HNE on the signaling pathways controlling cyclooxygenase-2 (COX-2) and
interleukin-6 (IL-6) expression in view of their putative role in OA
pathophysiology. HNE dose-dependently decreased basal and tumour necrosis factor
alpha (TNF-alpha)-induced IL-6 expression while inducing COX-2 expression and
prostaglandin E2 (PGE2) release. In a similar pattern, HNE induces changes in
osteoblast markers as well as PGE2 and IL-6 release in normal osteoblasts. Upon
examination of signaling pathways involved in PGE2 and IL-6 production, we found
that HNE-induced PGE2 release was abrogated by SB202190, a p38 mitogen-activated
protein kinase (MAPK) inhibitor. Overexpression of p38 MAPK enhanced HNE-induced
PGE2 release. In this connection, HNE markedly increased the phosphorylation of
p38 MAPK, JNK2, and transcription factors (CREB-1, ATF-2) with a concomitant
increase in the DNA-binding activity of CRE/ATF. Transfection experiments with a
human COX-2 promoter construct revealed that the CRE element (-58/-53 bp) was
essential for HNE-induced COX-2 promoter activity. However, HNE inhibited the
phosphorylation of IkappaBalpha and subsequently the DNA-binding activity of
nuclear factor-kappaB. Overexpression of IKKalpha increased TNF-alpha-induced IL
6 production. This induction was inhibited when TNF-alpha was combined with HNE.
These findings suggest that HNE may exert multiple effects on human OA
osteoblasts by selective activation of signal transduction pathways and
alteration of osteoblastic phenotype expression and pro-inflammatory mediator
production.
PMID- 17042957
TI - Accumulation of low density lipoprotein associated cholesterol in calcifying
vesicle fractions correlates with intimal thickening in thoracic aortas of
juvenile rabbits fed a supplemental cholesterol diet.
AB - BACKGROUND: It has been shown that calcifying vesicles play an important role in
aortic calcification and that cholesterol content in the isolated vesicle
fraction is increased when rabbits are fed supplemental cholesterol diets.
Whether lipoprotein-associated cholesterols and other lipids are also increased
in the vesicle fraction and whether the increase correlates with atherosclerosis
remain unknown. RESULTS: Fourteen juvenile male rabbits fed an atherogenic diet
containing 0.5% cholesterol and 2% peanut oil for 3 months developed varying
degrees of hypercholesterolemia and intimal thickening in the ascending thoracic
aorta. The correlation between these two parameters was insignificant, and likely
attributable to the use of small numbers of rabbits in this study. Despite this
lack of correlation, we demonstrate that the accumulation of cholesterol in
calcifying vesicle fractions obtained from the collagenase-digested aorta
fragments correlates well with intimal thickening (r2 = 0.98, p < 0.0001). To a
smaller degree, the correlation was also significant between intimal thickening
and the cholesterol accumulation in the microsomal and post-vesicle fractions.
The cholesterol supplemental diet increased the low density lipoprotein
cholesterol (LDL-C) content in calcifying vesicle fractions by 3-fold but did not
affect the triglyceride content. High density lipoprotein-cholesterol (HDL-C) and
very low-density lipoprotein cholesterol (VLD-C) were absent in calcifying
vesicle fractions. CONCLUSION: When limited numbers of rabbits are used, LDL-C
accumulation in calcifying vesicle fractions is a better biomarker for
atherosclerosis than LDL-C levels in the serum. The close association of LDL-C
with calcifying vesicles may play an important role in atherosclerosis and
calcification.
PMID- 17042958
TI - A framework for protein structure classification and identification of novel
protein structures.
AB - BACKGROUND: Protein structure classification plays a central role in
understanding the function of a protein molecule with respect to all known
proteins in a structure database. With the rapid increase in the number of new
protein structures, the need for automated and accurate methods for protein
classification is increasingly important. RESULTS: In this paper we present a
unified framework for protein structure classification and identification of
novel protein structures. The framework consists of a set of components for
comparing, classifying, and clustering protein structures. These components allow
us to accurately classify proteins into known folds, to detect new protein folds,
and to provide a way of clustering the new folds. In our evaluation with SCOP
1.69, our method correctly classifies 86.0%, 87.7%, and 90.5% of new domains at
family, superfamily, and fold levels. Furthermore, for protein domains that
belong to new domain families, our method is able to produce clusters that
closely correspond to the new families in SCOP 1.69. As a result, our method can
also be used to suggest new classification groups that contain novel folds.
CONCLUSION: We have developed a method called proCC for automatically classifying
and clustering domains. The method is effective in classifying new domains and
suggesting new domain families, and it is also very efficient. A web site
offering access to proCC is freely available at
http://www.eecs.umich.edu/periscope/procc.
PMID- 17042959
TI - Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides.
AB - BACKGROUND: Evaluation of microbicides for prevention of HIV-1 infection in
macaque models for vaginal infection has indicated that the concentrations of
active compounds needed for protection by far exceed levels sufficient for
complete inhibition of infection in vitro. These experiments were done in the
absence of seminal plasma (SP), a vehicle for sexual transmission of the virus.
To gain insight into the possible effect of SP on the performance of selected
microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was
determined. METHODS: The inhibitory activity of compounds against the X4 virus,
HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator
cells and quantitated by measuring beta-galactosidase induced by infection. The
virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP), the
only microbicide provided in water insoluble, micronized form, in the presence of
SP was measured. RESULTS: The HIV-1 inhibitory activity of the polymeric
microbicides, poly(naphthalene sulfonate), cellulose sulfate, carrageenan, CAP
(in soluble form) and polystyrene sulfonate, respectively, was considerably
(range approximately 4 to approximately 73-fold) diminished in the presence of SP
(33.3%). Formulations of micronized CAP, providing an acidic buffering system
even in the presence of an SP volume excess, effectively inactivated HIV-1
infectivity. CONCLUSION: The data presented here suggest that the in vivo
efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might
become at least partly compromised by the inevitable presence of SP. These
possible disadvantages could be overcome by combining the respective polymers
with acidic pH buffering systems (built-in for formulations of micronized CAP) or
with other anti-HIV-1 compounds, the activity of which is not affected by SP,
e.g. reverse transcriptase and zinc finger inhibitors.
PMID- 17042960
TI - Cdt1 revisited: complex and tight regulation during the cell cycle and
consequences of deregulation in mammalian cells.
AB - In eukaryotic cells, replication of genomic DNA initiates from multiple
replication origins distributed on multiple chromosomes. To ensure that each
origin is activated precisely only once during each S phase, a system has evolved
which features periodic assembly and disassembly of essential pre-replication
complexes (pre-RCs) at replication origins. The pre-RC assembly reaction involves
the loading of a presumptive replicative helicase, the MCM2-7 complexes, onto
chromatin by the origin recognition complex (ORC) and two essential factors, CDC6
and Cdt1. The eukaryotic cell cycle is driven by the periodic activation and
inactivation of cyclin-dependent kinases (Cdks) and assembly of pre-RCs can only
occur during the low Cdk activity period from late mitosis through G1 phase, with
inappropriate re-assembly suppressed during S, G2, and M phases. It was
originally suggested that inhibition of Cdt1 function after S phase in vertebrate
cells is due to geminin binding and that Cdt1 hyperfunction resulting from Cdt1
geminin imbalance induces re-replication. However, recent progress has revealed
that Cdt1 activity is more strictly regulated by two other mechanisms in addition
to geminin: (1) functional and SCFSkp2-mediated proteolytic regulation through
phosphorylation by Cdks; and (2) replication-coupled proteolysis mediated by the
Cullin4-DDB1Cdt2 ubiquitin ligase and PCNA, an eukaryotic sliding clamp
stimulating replicative DNA polymerases. The tight regulation implies that Cdt1
control is especially critical for the regulation of DNA replication in mammalian
cells. Indeed, Cdt1 overexpression evokes chromosomal damage even without re
replication. Furthermore, deregulated Cdt1 induces chromosomal instability in
normal human cells. Since Cdt1 is overexpressed in cancer cells, this could be a
new molecular mechanism leading to carcinogenesis. In this review, recent
insights into Cdt1 function and regulation in mammalian cells are discussed.
PMID- 17042962
TI - Neuroaxial anesthesia in a patient with progressive systemic sclerosis : case
presentation and review of the literature on systemic sclerosis.
AB - BACKGROUND: Systemic sclerosis (SSc), a progressive disease characterized by
excessive accumulation of connective tissue components. Although most patients
have long survival, some of them progress rapidly to death. Pulmonary system
involvement and pulmonary hypertension are the most frequent cause of death. When
the patient with SSc is to be operated, the anesthetic procedure could be a
serious problem. In this article, we report a combined spinal--epidural technique
in a patient with progressive SSc and the anesthetic considerations that could be
recommended for these patients. CASE PRESENTATION: A 68-year-old woman who had a
history of progressive systemic sclerosis, pulmonary fibrosis, kyphoscoliosis and
decreased oral apertura underwent total hip arthroplasty. This operation was
performed successfully under combined spinal epidural anesthesia. CONCLUSION:
Systemic sclerosis is a complex disease that involves multiple organ systems.
Every aspects of anesthetic care may be altered or hindered by the pathogenesis
of disease. Although the choice of regional or general anesthesia is unclear, to
choose combined spinal epidural anesthesia may be useful.
PMID- 17042961
TI - Inactivation of tumor suppressor Dlg1 augments transformation of a T-cell line
induced by human T-cell leukemia virus type 1 Tax protein.
AB - BACKGROUND: The interaction of human T-cell leukemia virus type 1 (HTLV-1) Tax1
protein with the tumor suppressor Dlg1 is correlated with cellular
transformation. RESULTS: Here, we show that Dlg1 knockdown by RNA interference
increases the ability of Tax1 to transform a mouse T-cell line (CTLL-2), as
measured interleukin (IL)-2-independent growth. A Tax1 mutant defective for the
Dlg1 interaction showed reduced transformation of CTLL-2 compared to wild type
Tax1, but the transformation was minimally affected by Dlg1 reduction. The few
Tax1DeltaC-transduced CTLL-2 cells that became transformed expressed less Dlg1
than parental cells, suggesting that Dlg1-low cells were selectively transformed
by Tax1DeltaC. Moreover, all human T-cell lines immortalized by HTLV-1, including
the recombinant HTLV-1-containing Tax1DeltaC, expressed less Dlg1 than control T
cell lines. CONCLUSION: These results suggest that inactivation of Dlg1 augments
Tax1-mediated transformation of CTLL-2, and PDZ protein(s) other than Dlg1 are
critically involved in the transformation.
PMID- 17042964
TI - Antimicrobial activity of some ethnomedicinal plants used by Paliyar tribe from
Tamil Nadu, India.
AB - BACKGROUND: Antimicrobial activity of 18 ethnomedicinal plant extracts were
evaluated against nine bacterial strains (Bacillus subtilis, Staphylococcus
aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli,
Klebsiella pneumonia, Pseudomonas aeruginosa, Ervinia sp, Proteus vulgaris) and
one fungal strain (Candida albicans). The collected ethnomedicinal plants were
used in folk medicine in the treatment of skin diseases, venereal diseases,
respiratory problems and nervous disorders. METHODS: Plants were collected from
Palni hills of Southern Western Ghats and the ethnobotanical data were gathered
from traditional healers who inhabit the study area. The hexane and methanol
extracts were obtained by cold percolation method and the antimicrobial activity
was found using paper disc diffusion method. All microorganisms were obtained
from Christian Medical College, Vellore, Tamil Nadu, India. RESULTS: The results
indicated that out of 18 plants, 10 plants exhibited antimicrobial activity
against one or more of the tested microorganisms at three different
concentrations of 1.25, 2.5 and 5 mg/disc. Among the plants tested, Acalypha
fruticosa, Peltophorum pterocarpum, Toddalia asiatica,Cassia auriculata, Punica
granatum and Syzygium lineare were most active. The highest antifungal activity
was exhibited by methanol extract of Peltophorum pterocarpum and Punica granatum
against Candida albicans. CONCLUSION: This study evaluated the antimicrobial
activity of the some ethnomedicinal plants used in folkloric medicine. Compared
to hexane extract, methanol extract showed significant activity against tested
organisms. This study also showed that Toddalia asiatica, Syzygium lineare,
Acalypha fruticosa and Peltophorum pterocarpum could be potential sources of new
antimicrobial agents.
PMID- 17042965
TI - Endotracheal tube migration following transoesophageal echocardiography probe
placement in a child.
PMID- 17042963
TI - High prevalence of ACE DD genotype among north Indian end stage renal disease
patients.
AB - BACKGROUND: The Renin-Angiotensin system (RAS) is a key regulator of both blood
pressure and kidney functions and their interaction. In such a situation, genetic
variability in the genes of different components of RAS is likely to contribute
for its heterogeneous association in the renal disease patients. Angiotensin
converting enzyme-1 (ACE-1) is an important component of RAS which determines the
vasoactive peptide Angiotensin-II. METHODS: In the present study, we have
investigated 127 ESRD patients and 150 normal healthy controls from north India
to deduce the association between ACE gene polymorphism and ESRD. The inclusion
criteria for patients included a constantly elevated serum creatinine level above
normal range (ranging from 3.4 to 15.8) and further the patients were recommended
for renal transplantation. A total of 150 normal healthy controls were also
genotyped for ACE I/D polymorphism. The criterion of defining control sample as
normal was totally based on the absence of any kidney disease determined from the
serum creatinin level. Genotyping of ACE I/D were assayed by polymerase chain
reaction (PCR) based DNA amplification using specific flanking primers Based on
the method described elsewhere. RESULTS: The difference of DD and II genotypes
was found highly significant among the two groups (p = 0.025; OR = 3.524; 95% CI
= 1.54-8.07). The combined genotype DD v/s ID+II comparison validated that DD
genotype is a high risk genotype for ESRD (p = 0.001; OR = 5.74; 95% CI limit =
3.4-8.5). However, no correlation was obtained for different biochemical
parameters of lipid profile and renal function among DD and non DD genotype.
Interestingly, approximately 87% of the DD ESRD patients were found hypertensive
in comparison to the 65% patients of non DD genotype CONCLUSION: Based on these
observations we conclude that ACE DD genotype implicate a strong possible role in
the hypertensive state and in renal damage among north Indians. The study will
help in predetermining the timing, type and doses of anti-hypertensive therapy
for ESRD patients.
PMID- 17042966
TI - An unusual adverse effect of an accidental epidural morphine overdose.
PMID- 17042967
TI - Analgesia for venous cannulation by subcutaneous infiltration: effect of
lidocaine concentration.
PMID- 17042968
TI - Securing the airway of a 'super sized' patient: another use for the Aintree
Catheter.
PMID- 17042969
TI - 'Spraying the cords'.
PMID- 17042970
TI - Pancreatitis and hypertriglyceridaemia.
PMID- 17042971
TI - First national guidelines will help better control HIV/AIDS in China.
PMID- 17042972
TI - Guidelines for diagnosis and treatment of HIV/AIDS in China (2005).
PMID- 17042973
TI - Association between Nef-specific CD8 T-cell responses and disease progression in
HIV-1 subtype B infection.
AB - BACKGROUND: The correlation between HIV-1 Nef-specific CD8 T-cell responses and
markers of HIV-1 disease progression still remains unclear. This study analysed
and compared the role of HIV-1 Nef-specific CD8 T-cell responses in patients with
different disease status. METHODS: Two groups of patients with HIV-1 subtype B
infection were selected according to CD4 count and clinical manifestations: long
term nonprogressors (LTNPs, n = 20) and advanced progressors (APs, CD4 count <
500 cells/microl, n = 34). Nef-specific CD8 T-cell responses were studied by
interferon-gamma ELISpot assay against 3 pools of HIV-Nef peptides. RESULTS: Nef
specific CD8 T-cell responses did not correlate with viral load or CD4 count in
all patients and no significant differences were found in the magnitude of Nef
specific CD8 T-cell responses between groups LTNPs and APs (670 SFC/10(6)
peripheral blood mononuclear cells vs 1107 SFC/10(6) peripheral blood mononuclear
cells, P = 0.255). Further comparisons showed that there were also no significant
correlations observed in group LTNPs, but Nef-specific CD8 T cells correlated
negatively with viral load (r = -0.397, P = 0.020) and positively with CD4 count
(r = 0.364, P = 0.034) in group APs. CONCLUSION: These data suggest that
different correlation patterns between Nef-specific CD8 T-cell responses and
disease progression exist in LTNPs and APs. Although a negative association was
observed with concurrent plasma HIV RNA in APs, Nef-specific CD8 T-cell responses
might fail to play a protective role in different stages of HIV-1 infection.
PMID- 17042974
TI - Identification of HIV-1 specific T lymphocyte responses in highly exposed
persistently seronegative Chinese.
AB - BACKGROUND: Studies of highly exposed persistently seronegative (HEPS)
individuals may provide valuable information on mechanisms of protection and on
vaccine design. Cellular immune responses play a critical role in containing
human immunodeficiency virus. However, the cellular immune responses in HEPS
individuals have not been thoroughly assessed at the entire viral genome level.
METHODS: Ten HEPS Chinese with a history of frequent penetrative vaginal
intercourse (mean frequency, at least once a week), with some unprotected sexual
contact occurring in the weeks or days immediately before enrollment, 25 HIV-1
seropositive individuals, 10 HIV-1-seronegative healthy individuals with low-risk
sexual behavior and no history suggestive of exposure to HIV-1 infection were
enrolled. HIV-1-specific T cell responses were comprehensively analyzed by an
interferon-gamma Elispot assay against 770 overlapping peptides spanning all HIV
1 proteins. RESULTS: HIV-1-specific T-cell responses of interferon-gamma
secretion were identified in 3 (30%) out of 10 HEPS individuals; the specific
cytotoxic T lymphocytes were targeted at Pol (2/10), Env (2/10), and Tat (1/10).
HIV-1-specific T-cell responses of interferon-gamma secretion were identified in
20 (80%) out of 25 seropositive intravenous drug users (IDUs), revealing that all
HIV-1 proteins and protein subunits could serve as targets for HIV-1-specific
CD8(+) T cell responses with 85% recognizing Gag, 80% recognizing Nef, 75%
recognizing Pol, 60% recognizing Env, 55% recognizing Vpu, 45% recognizing Vpr,
20% recognizing Vif, 20% recognizing Tat and 15% recognizing Rev in these
seropositive individuals. None of the seronegative healthy individuals gave the
positive T-cell responses. CONCLUSIONS: About 30% of HEPS Chinese mounted HIV-1
specific T cell immune responses. Cell-mediated immunity against HIV-1 may be
developed through non-productive infections.
PMID- 17042975
TI - Genetic characterization of three CRF01_AE full-length HIV type 1 sequences from
Fujian Province, China.
AB - BACKGROUND: One of the major characteristics of the human immunodeficiency virus
type 1 (HIV-1) is its unusually high degree of genetic variability, which
involves in genetic diagnosis, subtyping, vaccine design, and epidemiology. HIV-1
CRF01_AE is a main prevalent HIV-1 recombinant strain in China. In this study,
three full-length CRF01_AE genomes from Fujian Province, China were cloned,
sequenced, and analyzed; and the further genetic diversity defining and
epidemiologic analysis were carried out. METHODS: Proviral DNA was extracted from
non-cultured peripheral blood mononuclear cells, the near full-length HIV-1
genome was amplified and the PCR products were cloned into pCR-XL-TOPO vector and
sequenced. 5'-long terminal repeat (LTR) and 3'-LTRs were amplified by additional
independent PCR and cloned into pMD18T vector. Gene-based phylogenic tree was
constructed and genetic distances were calculated by MEGA 3.1. Simplot was used
for Bootscan analysis. RESULTS: The phylogeny and genetic distance analysis of
the three near full-length sequences confirmed that these three samples clustered
with CRF01_AE isolates, more close to Thailand CRF01_AE strain CM240, and were
distantly related to African CRF01_AE strain 90CF402. Analysis of their genomic
organization revealed the presence of nine potential open reading frames. There
were no major deletions, rearrangements, or insertions in the three sequences,
but an in-frame stop codon was found in tat gene of Fj051. LTRs of the three
sequences contained a few nucleotides mutation. We did not find new mosaic
recombinant in the three sequences. The V3 motif was GPGQ in all the three
sequences, and there were only few amino acids differences in all three V3 loop
sequences. CONCLUSION: This report reveals the background of the three full
length CRF01_AE genomes, the most dominantly circulating HIV-1 strain in Fujian
Province, China. The work is essential for the design and development of an
effective AIDS vaccine for the region.
PMID- 17042976
TI - CD4+ T cell-mediated presentation of non-infectious HIV-1 virion antigens to HIV
specific CD8+ T cells.
AB - BACKGROUND: The mechanism of chronic immune activation and impairment of HIV
specific immune responses during chronic infection is not fully understood.
However, it is known that high immune activation leads to more rapid progression
to AIDS. We hypothesize that CD4(+) T cell-mediated viral antigen presentation
contributes to this pathologic immune activation in HIV-infected individuals.
METHODS: HIV-specific T cells, responding to noninfectious HIV-1 virions as
antigen, were measured by flow cytometric assays. These experimental conditions
reflect the in vivo condition where noninfectious HIV-1 represents more than 99%
of the antigens. RESULTS: CD4(+) T cells purified from HIV-infected individuals
were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1
specific CD8(+) T cells. Cross presentation required the entry of HIV-1 to CD4(+)
T cells and antigen translocation from endoplasmic reticulum to the Golgi
complex. Blocking CD4(+) mediated activation of HIV-specific CD8(+) T cells and
redirecting the viral antigens to antigen presenting cells improved HIV-specific
T cell responses. CONCLUSIONS: One possible cause of chronic immune activation
and impairment of HIV-1 specific T cell responses is represented by HIV-1
harboring CD4(+) T cells cross presenting HIV-1 antigen to activate CD8(+) T
cells. This new mechanism provides the first evidence that cross presentation of
noninfectious HIV-1 virions play a role in the immunopathogenesis of HIV-1
infection.
PMID- 17042977
TI - Protection of human islets from induction of apoptosis and improved islet
function with HO-1 gene transduction.
AB - BACKGROUND: Islet transplantation represents an ideal therapeutic approach for
treatment of type 1 diabetes but islet function and regeneration may be
influenced by necrosis or apoptosis induced by oxidative stress and other
insults. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in the catabolism of
heme into biliverdin, releasing free iron and carbon monoxide. It has also been
reported to be an antioxidant enzyme which can improve the function of grafted
islets by cytoprotection via free radical scavenging and apoptosis prevention. In
the present study, we investigated whether transduction of HO-1 genes into human
islets with an adenovirus vector has cytoprotective action on islets cultured in
vitro and discuss this method of gene therapy for clinical islet transplantation.
METHODS: Cadaveric pancreatic islets were isolated and purified in vitro.
Transduction efficiency of islets was determined by infecting islets with
adenovirus vector containing the enhanced green fluorescent protein gene (Ad
EGFP) at multiplicities of infection (MOI) of 2, 5, 10, or 20. Newly isolated
islets were divided into three groups: EGFP group, islets transduced with Ad-EGFP
using MOI = 20; HO-1 group, transduced with adenovirus vectors containing the
human HO-1 gene using MOI = 20; and control group, mock transduced islets.
Insulin release after glucose stimulation of the cell lines was determined by a
radioimmunoassay kit and the stimulation index was calculated. Flow cytometry was
used to detect apoptotic cells in the HO-1 group and in the control group after
induction by recombinant human tumor necrosis factor-alpha (rTNFalpha) and
cycloheximide (CHX) for 48 hours. RESULTS: Adenovirus vectors have a high
efficiency of gene transduction into adult islet cells. Transduction of islets
with the Ad-EGFP was most successful at MOI 20, at which MOI fluorescence was
very intense on day 7 after transduction and EGFP was expressed in cultured islet
cells for more than four weeks in vitro. The insulin release in the control group
was (182.36 +/- 58.96) mIU/L after stimulation by high glucose media (16.7
mmol/L), while insulin release from the HO-1 group and the EGFP group were
(270.09 +/- 89.37) mIU/L and (175.95 +/- 75.05) mIU/L respectively. Compared to
the control group and the EGFP group, insulin release in the HO-1 group increased
significantly (P < 0.05). After treatment with rTNFalpha and CHX the apoptotic
ratio of islet cells was (63.09 +/- 10.86)% in the HO-1 group, significantly
lower than (90.86 +/- 11.25)% in the control group (P < 0.05). CONCLUSIONS:
Transduction of human islets with Ad-HO-1 can protect against TNF-alpha and CHX
mediated cytotoxicity. The HO-1 gene also appears to facilitate insulin release
from human islets. Transduction of donor islets with the adenovirus vector
containing an HO-1 gene might have potential value in clinical islet
transplantation.
PMID- 17042978
TI - Antigen-specific tolerance induced by IL-10 gene modified immature dendritic
cells in experimental autoimmune myocarditis in rats.
AB - BACKGROUND: Experimental autoimmune myocarditis (EAM) in rats is a T-cell
mediated disorder. The initiation and maintenance of autoimmune responses in EAM
depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic
immunomodulatory cytokine that functions at different levels of the immune
response, so it has emerged as a promising therapeutic factor for the treatment
of autoimmune/inflammatory diseases. This study was designed to test the
hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells
(iDCs) ameliorate EAM and to explore the underlying mechanisms. METHODS: EAM was
induced using the methods of cardiac myosin immunization on day 0 and day 7.
Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated
without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was
analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10
plasmid. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected
iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were
injected intravenously for treatment 5 days after the first immunization. On day
21, HE staining was performed to detect the myocardial inflammation and T
lymphocyte proliferation assay was used to determine the effects of IL-10 gene
transfected iDC on autoreactive T cell proliferation. Expression of IkappaB, the
inhibitor of NF-kappaB pathway, was determined by Western blot. RESULTS: BMDCs
generated in a medium supplemented with granulocyte-macrophage-colony-stimulating
factor (GM-CSF) were relatively immature, as determined by flow cytometry.
However, stimulation with LPS induced these cells to become mature (m) DCs with
higher levels of surface major histocompatibility complex (MHC)-II and
costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL
10 transfected iDC, ameliorated the histopathological severity of the myosin
induced-EAM, and the effect was lost after the DCs underwent maturation induced
by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen
specific T cell responses towards cardiac myosin. IkappaB protein was up
regulated significantly in the IL-10 gene modified iDC group. CONCLUSIONS: IL-10
gene modified iDC induced antigen-specific tolerance in EAM. The underlying
mechanisms may be related to costimulatory molecules down-regulation and NF
kappaB pathway inhibition.
PMID- 17042979
TI - Microsurgical treatment of craniopharyngiomas: report of 284 patients.
AB - BACKGROUND: Generally, total surgical removal of craniopharyngioma results in
satisfactory outcome with a low recurrence rate, however, the location of the
tumor and its adherence to the hypothalamic structures can make the operation
difficult. The goal of the present study was to assess the outcome of
craniopharyngiomas in 284 patients treated surgically. METHODS: A total of 284
patients (151 men and 133 women) with craniopharyngioma were treated surgically
by our neurosurgeons from January 1996 to March 2006. Among them, 226 (79.6%)
patients were adults (15 years of age or older; mean, 35.8 +/- 10.6), 58 (20.4%)
were children (14 years of age or younger; mean, 9.1 +/- 3.8). The diameter of
the tumors were 2.0 - 9.0 cm (mean, 36.54 +/- 11.4). The tumors were classified
into the superior (23 patients) and inferior ventricular (261) types according to
the location of the tumor relative to the third ventricular floor. For the
patients with craniopharyngioma of inferior ventricular type, pterional approach
was used in 191 (67.3%) patients, subfrontal approach in 17 (6.0%), and
translamina terminalis through frontobasal interhemispheric approach in 53
(18.7%). For those with the tumors of superior ventricular type, transcallosal
approach into the anterior third ventricle was done in 10 (3.5%) patients, and
the lamina terminalis approach in 13 (4.6%). Of the 284 patients, 204 (71.8%)
were followed up for 0.5 to 8 years (mean, 2.1 +/- 1.8), including 162 patients
received total tumor removal, and 37 underwent subtotal or partial removal.
RESULTS: Total, subtotal and partial removal of the tumors were achieved in 237
(83.5%), 34 (12.0%) and 13 (4.5%) patients, respectively. The pituitary stalk was
preserved in 176 (62.0%) patients, severed in 52 (18.3%), and unidentified in 56
(19.7%). Twelve (4.2%) patients died within one month after the surgery. During
the follow-up, 23 (14.1%) patients experienced tumor recurrence 1.0 - 3.5 years
(mean, 1.8 +/- 1.6) after total tumor removal, and 24 (64.9%) had recurrent tumor
0.25 - 1.5 years (mean, 0.5 +/- 0.4) after subtotal or partial resection. Normal
activities of daily living were regained in 63 (80%) patients, independence in 29
(14.2%), and daily life with assistance in 9 (4.4%). Four (2.0%) patients died
0.9 - 3 years (mean, 1.6 +/- 1.4) after discharge from hospital, 3 of them died
of hypothalamic deficiency. CONCLUSIONS: We can protect the hypothalamic
structures and its perforating arteries by choosing surgical approaches according
to the location of craniopharygioma relative to the third ventricular floor. The
mortality, morbidity, and recurrence rate in patients received total resection
are lower than those of patients underwent subtotal or partial resections. In
addition, preservation of the pituitary stalk is critical when total tumor
resection is feasible.
PMID- 17042980
TI - Vascular endothelial growth factor expressing mesenchymal stem cells improves
cardiac function in chronic myocardial infarction in pigs.
PMID- 17042981
TI - Teaching chronic obstructive airway disease patients using a metered-dose
inhaler.
PMID- 17042982
TI - [Lipid lowering goals in high risk and very high cardiovascular risk patients: a
reasonable challenge?].
AB - OBJECTIVE: The last modifications of the National Cholesterol Education Program
(NCEP) indicate some lower therapeutic targets of low density protein cholesterol
(LDL-c) in patients with very high vascular risk. Our study aims to establish the
degree of compliance of the therapeutic targets defined by these modifications.
PATIENTS AND METHOD: Descriptive and cross sectional study of patients from a
cardiovascular clinic. Low-density lipoprotein cholesterol (LDL-c) was calculated
and targets were established according the new update of NCEP-ATP III. RESULTS:
836 patients, 625 (75%) with HR and 211(25%) with VHR were studied 45% of HR and
67% of VHR were receiving treatment with statins (p < 0.001) but only 38% of HR
and 15% of VHR achieved target LDL-c levels. The percentage of patients who could
achieve LDL-goals using the maximum approved dose of the statins plus other lipid
lowering drug was calculated: The 31% of HR and 51% of VHR were unable to achieve
the LDL-c targets. CONCLUSIONS: Only 15% of very high risk patients achieve
target levels of LDL-c according to the new NCEP-ATP III recommendations. Even
using maximum dose of statins in combination with other lipid lowering drugs,
less than half of the patients will be able to achieve LDL-c goal (< 70 mg/dl).
PMID- 17042983
TI - [Analysis of the characteristics of patients with bladder cancer diagnosed of
multiple neoplasms in the health district of Leon (Spain)].
AB - OBJECTIVE: We analyzed the characteristics of the patients with bladder neoplasms
who developed a multiple malignant primary neoplasm (MMPN) in the health district
of Leon, the impact on survival and the prognostic variables. MATERIAL AND
METHODS: We have used the data from the Tumor Registry of the Hospital of Leon
and selected all those patients who were diagnosed of a bladder tumor between
1993 and 2002. They were classified into two groups: the first with 71 patients
with MMPN and a second group with 159 patients with single bladder tumors
diagnosed between 1996 and 1997. RESULTS: Incidence of MMPN was of 7.1 percent.
More than half of the patients had familial oncologic background. The second most
frequently diagnosed neoplasms were urologic, followed by gastrointestinal and
respiratory. Survival of patients with MMPN was 21 percent lower than single
neoplasms. Variables with prognosis significance were the stage of the second
neoplasm, diagnosis of a second urologic neoplasm and surgery treatment for the
second tumor. CONCLUSIONS: MMPN in patients with bladder tumors are frequent in
our geographic area. The high frequency of familial oncologic antecedents in
these patients suggest a genetic background. Prognosis of MMPN patients is worse
than single tumors patients, but no differences were observed regarding prognosis
in patients with synchronous or metachronous MMPN.
PMID- 17042984
TI - [Effectiveness of a quality improvement intervention in blood pressure control in
Primary Care].
AB - INTRODUCTION AND OBJECTIVES: To evaluate the effectiveness of a quality
improvement intervention on professionals sanitary in blood pressure control in
hypertensive patients. METHODS: Quality improvement trials with cuasi
experimental design. Two primary care health centres. One centre was assigned
intervention group (7 family doctors and 419 patients) and the other was control
group (7 family doctors and 419 patients). The quality improvement intervention
consisted of a combined program comprising audit, feedback, training sessions
about main hypertension clinical guidelines during 6 months. The main measurement
were blood pressure, lipid levels, diabetes, smoking and body index mass,
antihypertensive drugs and record treatment adherence and therapeutic plan in
march 2002 the baseline measurement and march 2004 the post intervention.
RESULTS: In study group blood pressure systolic and diastolic decreased 8.16/3.71
mmHg and control group increased 1.56/0.13 mmHg, respectively. The intervention
effect was a drop of 9.72 mmHg (IC 95%: 7.50-11.94) and diastolic blood pressure
in 3.84 mmHg (IC 95%: 2.40-5.28). The rate of hypertensive patients with blood
pressure < 140/90 mmHg increased from 37.5% to 68.8% in study group, without
changes in control group (p < 0.05). The drugs and combination drugs prescribed
increased in both group, while the records of therapeutics plans and adherence
increased only in intervention group (p < 0.05). CONCLUSIONS: The quality
improvement intervention was associated to a systolic and diastolic blood
pressure reduction and a increase of rate patients with blood pressure
controlled.
PMID- 17042985
TI - [COPD, a public health problem].
AB - The fundamental etiologic factor of COPD is tobacco. This has a 9% prevalence in
Spain and although this rate is underestimated according to the last studies,
COPD generates about 39,000 hospital admissions per year. It has a re-admission
rate between 12% and 32%, infections being the fundamental cause. The average
care cost per patient from its diagnostic to death is 27,500 euro and we should
add a high percentage of employee absenteeism. Due to its chronic aspect, high
health care cost and possible improvement of the quality of life of patient, the
solution to the problem needs to have a more active involvement of the doctor who
attends these patients.
PMID- 17042986
TI - [Data and reflections on the current process of the multicenter clinical trial
assessment in Spain].
AB - The European Directive 2001/20/EC was intended, among other things, to simplify
and accelerate the start of multicenter clinical trials (MCT) in all European
Union countries. The Spanish regulation in force since May 2004 has failed to
achieve this. Because there is not a real single opinion in Spain, as given by a
single Research Ethics Committee, a key point to accelerate the MCT assessment,
less than 50% of the protocols are assessed in the maximum time of 60 days
established by the Directive. As a consequence in 2005 up to 29% of investigators
(twice as much as in 2003 percentage) had no time to recruit patients in the MCT,
since when the ethical-administrative process is finally completed, the
recruitment period has almost concluded, or even has finalized internationally.
Likewise, a 37% reduction in the percentage of investigators recruiting > 90% of
committed cases in MCT was observed between 2003 and 2005. All these differences
are statistically significant (p < 0.0001). These figures clearly show that Spain
needs urgent changes in the current regulation of MCT to be competitive in
clinical research in Europe.
PMID- 17042987
TI - [Classification criteria and clinical significance of the metabolic syndrome].
AB - The metabolic syndrome (MS) is a multifactorial entity (genetic and behavioral).
Its incidence and prevalence have risen dramatically, especially in Western
countries, where lifestyle is changing (high caloric intake of mostly saturated
fat, heavy alcohol consumption, smoking and little physical activity). It results
from the striking increase prevalence of obesity and is an increasingly
recognized factor for cardiovascular risk. The MS is defined in various ways. The
most recent NCEP and IDF definitions are simple and easy to use in clinical
practice. Nevertheless, a unique worldwide definition is still needed, as these
definitions show significant differences in some ethnic groups.
PMID- 17042988
TI - [Generalized seizure episode of metabolic origin].
PMID- 17042989
TI - [Extrapleural lesion in right upper lobe associated to lytic lesion of the fifth
right rib].
PMID- 17042990
TI - [Ungual alterations in patient with edemas in lower limbs].
PMID- 17042991
TI - [35 year old male with lumbar pain and fever after intravenous cocaine
consumption].
PMID- 17042992
TI - [Deep venous thrombosis of left arm and multiple enlarged lymph nodes].
PMID- 17042993
TI - [Persistent leukocytosis and hyperglycemia].
PMID- 17042994
TI - [Cyclosporine A in treatment of lupus nephritis resistant to cyclophosphamide and
mycophenolate mofetil: a case report].
PMID- 17042995
TI - [Hepatobiliary fasciolasis without eosinophilia].
PMID- 17042996
TI - [Metabolic bone disease: something more than medication].
PMID- 17042997
TI - [Vitamin D deficit as cause of latent tetany].
PMID- 17042998
TI - [Diaphragmatic hernia of Morgagni in the adult].
PMID- 17042999
TI - [Multidisciplinary access to Intensive Care Medicine].
PMID- 17043000
TI - [Doss porphyria without demonstrated enzyme deficit: a secondary porphyrinuria?].
PMID- 17043001
TI - [Fabry disease in Spain: first analysis of the response to enzyme replacement
therapy].
AB - BACKGROUND AND OBJECTIVE: Fabry disease is a X-linked lysosomal disorder caused
by a deficient activity of the enzyme alfa-galactosidase A. Lack of enzyme
activity results in progressive accumulation of globotriaosylceramide (Gb3)
leading to multiorgan dysfunction and early death. Enzyme replacement therapy
(ERT) has recently become available and the database Fabry Outcome Survey (FOS)
of Spain gives us the opportunity to asses the efficacy of this therapy. Our
objective is to describe the safety and the effects on renal, cardiac and
neurological (pain) aspects of ERT with agalsidase alfa. PATIENTS AND METHOD: The
effects of 1, 2, 3 and 4 years of ERT with agalsidase alfa on renal function
(assessed by estimated glomerular filtration rate), proteinuria, heart size
(assessed by echocardiography), arrhythmias, cardiac valvular anomalies and pain
(assessed by the need of concomitant pain therapy) were analyzed in 33 patients
under treatment. Safety of ERT was assessed by the reported infusion-related
reactions in FOS. RESULTS: Overall, treatment with agalsidase alfa stabilized
renal function, but the final result depends on the onset of ERT: there is a
tendency to stabilization of renal function in those patients with mild
deterioration of renal function, a tendency to improve in those patients with
moderate deterioration and to worse in those with severe deterioration of renal
function. Proteinuria and left ventricular heart size also estabilized under ERT,
and pain improved. TSE infusion-related reactions occurred with an incidence of
0.7%. CONCLUSIONS: ERT with agalsidase alfa is safe and stabilized the abnormal
clinical parameters observed in patients with Fabry disease.
PMID- 17043002
TI - [Linguistic adaptation and Spanish validation of the LANSS (Leeds Assessment of
Neuropathic Symptoms and Signs) scale for the diagnosis of neuropathic pain].
AB - BACKGROUND AND OBJECTIVE: This study was intended to achieve a linguistic
adaptation and validation into Spanish of the LANNS scale for the differential
diagnosis of neuropathic pain. MATERIAL AND METHOD: Cross-sectional validation
study carried out in two phases: first, cultural adaptation into Spanish
language, by means of a conceptual equivalence approach, including forward and
backward translations in duplicate and review by experts; and second, validation
study of the scale in patients with neuropathic, noniceptive and mixed pain, in
which the scale properties of reliability (internal consistency and inter-rater
agreement with kappa and intra-class correlation coefficients) and validity (ROC
curves analisys, agreement with reference diagnosis and determination of
sensitivity, specificity and positive and negatives predictive values) were
evaluated. RESULTS: A total of 156 subjects (90 women, 58.4%), 89 with pain of
neuropathic origin (mean age [SD], 59.6 [19.4] years, 22 with mixed pain due to
radiculopathy) and 67 with nociceptive pain (66.6 [11.8] years) were included in
the study. Diagnosis of the type of pain was performed by standard clinical
criteria. The scale was administrated by trained interviewers, in duplicate and
blinded to the reference diagnosis. The scale showed good reliability (internal
consistency: Cronbach and Guttman split-half coefficients between 0.68 and 0.71;
inter-rater agreement: kappa coefficient of 0.70 and intra-class correlation
coefficients between 0.77 and 0.92) and validity for a cut-off value > or = 12
points, which represented the best value to discriminate between patients with
neuropathic and nociceptive components of pain (kappa coefficient = 0.70; CI 95%,
0.59-0.81; p < 0.0001); area under the curve, 0.929; (p < 0.0001); specificity,
89.4% (CI 95%, 79.4%-95.6%) and positive value, 91.1%; CI 95%, 82.6%-96.4%).
CONCLUSIONS: The Spanish version of the LANSS scale is reliable and valid for the
differential diagnosis of neuropathic pain.
PMID- 17043003
TI - [Usefulness of a new index for mortality after hospitalization in adults older
than 70 years].
AB - BACKGROUND AND OBJECTIVE: Walter et al developed and validated a mortality
prognostic index in older adults after hospitalization. Our objective was to
evaluate the Walter index utility and to compare it with Charlson index and
Barthel index in our population. PATIENTS AND METHOD: 455 patients were included
(224 men and 231 women), medium age was 81.4 years (range: 70-99), who were
discharged from 4 hospitals in Barcelona. At the moment of discharge Barthel
index, Charlson index and Walter index were administered. RESULTS: One year after
discharge the mortality was 40.66%. Medium Barthel index (standard deviation) was
64.42 (35.66), medium Charlson index was 3.07 (1.87), and medium Walter index was
5.34 (2.97). ROC curves analysis was done and it shows the bigger area under the
curve was Walter index (0.691). CONCLUSIONS: It's proved the Walter index utility
for mortality prognostic one year after discharge in elderly people who are
admitted in our hospitals. This could be useful to make a care design and
therapeutic objectives.
PMID- 17043004
TI - [Behcet disease].
PMID- 17043005
TI - [Neurological complications of celiac disease].
PMID- 17043006
TI - [Linoleic conjugated acid: current interest in human nutrition].
AB - Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of
linoleic acid. The major dietary sources of CLA are meat from rumiants and dairy
products. There are also foods enriched in CLA (by modification animal feed or
addition of commercial CLA from cartamo oil). However, the major isomer of CLA in
natural food is cis-9,trans-11 and commercial CLA contains approximately equal
amounts of cis-9,trans-11 and trans-10,cis-12 isomers. Although CLA is minor
component of the diet, at present CLA has provoked intense scientific research
accompanied by an advertising boom. This is due to the potential health effects
demonstrated in animal and cell culture experiments including effects on body
composition, specially a reduction in body fat mass and anticarcinogenic,
antidiabetogenic and immune modulating effects. The results obtained in human
volunteers are limited and even sometimes contradictory. This review focuses on
recently studies in humans. To draw conclusions on CLA's potential interest as a
functional ingredient, additional studies are needed to clearly define optimal
level of CLA intake, short and long term effects and side effects of each
individual CLA isomer in order to determine its safety and efficacy.
PMID- 17043007
TI - [Active hemosurveillance: a system that evaluates those post-transfusional
adverse effects that are not detected by the conventional hemosurveillance
system].
PMID- 17043008
TI - [Management of heart failure in short stay medical unit: mean stay, frequency and
predictors of readmission].
PMID- 17043009
TI - [Carbamazepine intoxication in a HIV patient under artiretroviral therapy].
PMID- 17043010
TI - [Hypogammaglobulinemia secundary to actinic enteritis].
PMID- 17043011
TI - [Liver abscess by Salmonella within a metastases of mullerian uterin cancer].
PMID- 17043012
TI - [Visceral leishmaniasis with cardiac affectation in an immunocompetent patient].
PMID- 17043013
TI - JAK2V617F mutations as cooperative genetic lesions in t(8;21)-positive acute
myeloid leukemia.
AB - Significant progress has been made in identifying genetic lesions that are
causally implicated in the pathogenesis of acute myeloid leukemia (AML). These
insights improve our understanding of the genetic basis of the disease, a
prerequisite for the development of novel therapeutic approaches.
PMID- 17043014
TI - Risk of second cancer after treatment of aggressive non-Hodgkin's lymphoma; an
EORTC cohort study.
AB - BACKGROUND AND OBJECTIVES: Second cancer has been associated with non-Hodgkin's
Lymphoma (NHL) treatment, but few studies have addressed this issue considering
specific treatments. DESIGN AND METHODS: We estimated risk by standardized
incidence ratios (SIR) and absolute excess risk (AER) based on general population
rates (European Network of Cancer Registries) in 748 patients (aged 15-82 years)
treated for aggressive NHL in four successive EORTC (European Organization for
Research on Treatment of Cancer) trials. RESULTS: All patients received fully
dosed CHOP-like chemotherapy, 65% received involved-field radiotherapy and 14%
high-dose treatment. Half of the patients needed salvage treatment and 37% were
followed for more than 10 years. The cause of death was NHL in 79% of the
patients; 4% died of second cancer (median survival 8.9 (0.8- 20.5) years).
Cumulative incidences (death from any cause being a competing event) were 5% and
11% for solid cancer and 1% and 3% for acute myeloid leukemia/myelodysplastic
syndrome at 10 and 15 years, respectively. Cancer risk appeared age-related: in
young patients high risks were observed for leukemia (SIR 16.7,95% CI 1.4
93.1,AER 5.0), Hodgkin's lymphoma (SIR 60.1,95% CI 12.4-175.2, AER 15.7),
colorectal cancer (SIR 12.5, 95% CI 2.6-36.5, AER 14.7) and lung cancer (SIR
15.4; 95% CI 4.2-39.4, AER 19.8), while risk in patients older than 45 years
matched than that in the normal population. The risk of cancer was significantly
raised by smoking and salvage treatment. INTERPRETATION AND CONCLUSIONS: Half of
the patients die of aggressive NHL before living long enough to experience second
cancer. Only young patients have a high risk of second cancer during follow-up
beyond 10 years.
PMID- 17043015
TI - The activity and toxicity of low dose clofarabine against relapsed or refractory
myeloma.
AB - Eight patients with refractory multiple myeloma were treated with clofarabine 4
mg/m2/day on days 1-5 of a 28 day cycle. No objective evidence of anti-myeloma
activity was observed (median time to progression of 52 days). All patients
experienced grade 3-4 neutropenia and a greater than 50% decrease in platelet
counts during treatment.
PMID- 17043016
TI - The risk of bleeding in thrombocytopenic patients with acute myeloid leukemia.
AB - BACKGROUND AND OBJECTIVES: Patients with acute myeloid leukemia are at risk of
bleeding. The risk factors for different severities of bleeding are poorly
studied. DESIGN AND METHODS: Data from Rebulla et al. were analyzed in an
exploratory analysis using multivariate Cox regression analyses for time-to-first
bleed with time-depend- ent covariates reflecting measures of clinical and
laboratory variables on the previous day. The relationships of the variables with
three bleeding categories were studied: mild bleeding (WHO grades 1 and 2)
clinically significant (bleeding grades 2, 3 and 4) and severe (bleeding grades 3
and 4). RESULTS: Bleeding of any severity occurred in 149 (58.4%) of 255
patients. There were 743 days of bleeding over 7335 patient-days of observation.
Risk factors for mild bleeding included increased body temperature and decreased
platelet count; the risk was decreased with administration of antifungal
medication or platelet transfusion on the previous day. Risk factors for
clinically significant bleeding included grade 1 bleeding on the previous day,
decreased platelet count and elevated body temperature. Decreased platelet count
and mild bleeding on the previous day were risk factors for severe bleeding.
Higher hemoglobin values were associated with a delay in the time-to-first
clinically significant bleed. INTERPRETATION AND CONCLUSIONS: These results
support clinical guidelines for increasing the platelet transfusion threshold in
the presence of fever and support the use of milder bleeding symptoms as an
outcome in clinical trials. The suggestion that hemo- globin concentration maybe
predictive of bleeding risk supports the hypothesis that this maybe a valuable
intervention in anemic thrombocytopenic patients at high risk of bleeding.
PMID- 17043017
TI - CARMA1 and chromosomal translocations in extranodal marginal zone B-cell
lymphomas of MALT type or diffuse large B-cell lymphomas.
AB - We analyzed the configuration of the CARMA1 gene, encoding a protein that closely
interacts with BCL10 and MALT1, in a series of 120 extranodal marginal zone B
cell lymphomas of MALT-type and 35 diffuse large B-cell lymphomas. Our study
suggests that CARMA1 is not targeted by chromosomal translocations in these
lymphoma entities.
PMID- 17043018
TI - Quantitative assessment of the transcriptional impact of mutations in the
3'untranslated region of the human beta-globin gene: application to the +1480 C-
>G mutation.
AB - The +1480 C -->G mutation in the 3' untranslated region (UTR) of the human beta
globin gene has been associated with beta-thalassemia. A previously vali- dated
in vitroexpression model used to assess the transcriptional impact of this 3'UTR
mutation demonstrated that it has no effect on beta-globin gene expression.
PMID- 17043019
TI - Identification of risk factors in atypical chronic myeloid leukemia.
AB - In the WHO classification atypical chronic myeloid leukemia (CML) has been
considered as a new distinct clinical entity included in the category of mixed
myeloproliferative/myelodysplastic disorders. Little is known about this uncommon
disease, whose incidence is about of one-two cases every 100 cases of Ph-positive
CML. We analyzed our series of 55 patients diagnosed as having aCML, with the aim
of identifying clinical factors of possible prognostic value on survival and
acute transformation.
PMID- 17043020
TI - Concomitant aberrant overexpression of RUNX1 and NCAM in regenerating bone marrow
of myeloid leukemia of Down's syndrome.
AB - BACKGROUND AND OBJECTIVES: Myeloid leukemia of Down's syndrome (ML-DS) has
characteristic biological features (e.g. expression of the truncated GATA1s),
which are different from those of non-DS childhood acute myeloid leukemias (AML).
The objective of this study was to investigate factors predisposing to the
development of ML-DS. DESIGN AND METHODS: We analyzed 134 bone marrow specimens
from 64 children with ML-DS and non-DS AML during chemotherapy and 7 specimens
from DS children with- out leukemia,who did not receive any chemotherapy,The
specimens were analyzed by multiparameter flow cytometry and quantitative reverse
transcriptase polymerase chain reaction for transcription factors involved in
hematopoiesis. RESULTS: Samples taken from children with ML-DS in complete
remission during chemotherapy aberrantly expressed CD56 (NCAM) at the surface of
monocytic and granulocytic cells. Compared to non-DS AML cases,children with ML
DS had a statistically significant higher proportion of CD56+ cells in the CD33+
fraction: 71%+/-6% vs. 4%+/-1% (p<0.00001). A significant decrease of the amount
of CD33+/CD56+ cells was observed during and after maintenance therapy. An
increased number of CD33+/CD56+ cells was also present (>85%) in children with DS
who did not receive chemotherapy, but showed a left-shift (due to infection),
compared with DS children without left-shift (<10% CD33+/CD56+ cells). Within the
CD33+/CD56+ fraction, RUNX1 was overexpressed more than 5-fold (p<0.02) compared
to CD33+/CD56- cells, whereas there were no differences regarding GATA1, SPI1,
ERG or ETS-2 levels. INTERPRETATION AND CONCLUSIONS: The combined overexpression
of RUNX1 and NCAM during stress hematopoiesis in children with DS might be a key
factor in the development of overt leukemia and/or in the growth advantage of the
malignant GATA1s clone in ML- DS.
PMID- 17043021
TI - The expression of PRDI-BF1 beta isoform in multiple myeloma plasma cells.
AB - The PRDM1 gene, a master regulator of plasma cells (PC), can generate two
transcription factor isoforms: PRDI-BF1alpha and PRDI-BF1beta. The present study
shows that purified human normal PC have a significantly lower levels of PRDI
BF1beta expression than that in tumoral PC isolated from multiple myeloma (MM)
(0.06+/-0.01 and 0.25+/-0.05, respectively; p<0.001). The role of this finding in
MM is discussed.
PMID- 17043022
TI - Diagnosis and treatment of vitamin B12 deficiency--an update.
AB - We represent an update on diagnosing and treatment of vitamin B12 deficiency.
Vitamin B12 deficiency should be suspected in all patients with unexplained
anaemia and/or neurological symptoms,as well as in patients at risk of developing
vitamin B12 deficiency such as the elderly and patients with intestinal diseases.
Measurement of plasma cobalamins is suggested as the primary analysis followed by
measurement of plasma methylmalonic acid in unsettled cases. Accumulating
evidence indicates that the biologically active cobalamin,plasma
holotranscobalamin (holoTC),may be superior to plasma cobalamins, and measurement
of holoTC is currently introduced in the clinical setting. No consensus exists
concerning evaluation of the cause for vitamin B12 deficiency,and pros and cons
on the different tests mainly aiming at evaluation of the function of the gastric
mucosa are presented. Once the diagnosis of vitamin B12 deficiency has been
confirmed efficient treatment can be ensured either by injections every 2-3 month
or by a daily dose of 1 mg vitamin B12.
PMID- 17043023
TI - The association of increased p14ARF/p16INK4a and p15INK4a gene expression with
proliferative activity and the clinical course of multiple myeloma.
AB - p14/p16 and p15 gene expression was assessed by quantitative polymerase chain
reaction in purified plasma cells (PC) from 52 patients with symptomatic multiple
myeloma (MM) and seven with smoldering MM in order to clarify the impact of these
genes on the proliferative activity of tumor cells and patients' outcome. p15
expression was lower in symptomatic MM than in smoldering SMM (-1.80
vs.1.51,p=0.026); similar results were observed for p14/p16. MM patients whose PC
displayed high p15 and/or p14/p16 expression had a lower percentage of S-phase PC
than the remaining cases (1.79%+/-1.35 vs. 3.04%+/-1.42, p=0.028), favorable
prognostic factors and longer survival (100% vs. 49%at 2.5 years; p=0.007).
PMID- 17043024
TI - A comparison of the in vitro cytotoxicity of daunorubicin and liposomal
daunorubicin in pediatric acute leukemia.
AB - Anthracyclines are effective in the treatment of leukemia, but their use is
limited because of cardiotoxicity. Liposomal daunorubicin (L-DNR) is potentially
less cardiotoxic than daunorubicin (DNR). We compared in vitro cytotoxicity in
pediatric acute leukemia samples and found no significant differences between
cytotoxicity of DNR and L-DNR.
PMID- 17043025
TI - Bortezomib plus dexamethasone as induction treatment prior to autologous stem
cell transplantation in patients with newly diagnosed multiple myeloma: results
of an IFM phase II study.
AB - BACKGROUND AND OBJECTIVES: Induction regimens prior to autologous stem cell
transplantation (ASCT) in newly diagnosed multiple myeloma patients usually
result in complete remission (CR) rates of <10%. The use of novel agents may
increase the CR rate before ASCT, which may improve post-transplantation response
and survival. DESIGN AND METHODS: This was a phase II, open-label trial of
bortezomib (1.3 mg/m(2), days 1,4,8,11) and dexamethasone (40 mg,days 1-4 and 9
12 for cycles 1-2,days 1-4 for cycles 3-4) administered for four 21-day cycles as
induction therapy in chemotherapy-naive myeloma patients. RESULTS: Of 52
recruited patients, 48 were eligible for the study. The overall response rate was
66% including 21% CR and 10% very good partial remission (>90% reduction of the M
component). Four patients had a minimal response, six had stable disease and five
had progression. One patient died after salvage therapy with VAD. The most common
side effects were gastrointestinal symptoms, peripheral neuropathy, and fatigue.
These were usually mild. Peripheral neuropathy was observed in 15 cases but was
grade 2-3 in only seven cases (14%). There was no deep vein thrombosis and no
hematologic toxicity greater than grade 2. Grade 3 infections were recorded in
five patients including three who had herpes zoster infections. Stem cell
collection was programmed in 44 cases and all patients had sufficient CD34+ cells
to perform one ASCT (> 2 x 10(6)/kg). INTERPRETATION AND CONCLUSION: This regimen
of bortezomib plus dexamethasone appears effective and well tolerated in newly
diagnosed myeloma patients.
PMID- 17043026
TI - The effect of silencing NKG2D through RNA interference on receptor functions in
interleukin-2-activated human natural killer cells.
AB - Natural killer (NK) cells are effectors of the innate immunity involved in tumor
surveillance. NKG2D is a potent activating receptor eliciting cytokine and
cytolytic NK responses upon recognition of tumor-associated ligands. We
engineered primary interleukin (IL)-2-activated human NK cells to express
constitutively low levels of NKG2D by lentiviral delivery of small interfering
RNA. NKG2D-mediated effector functions were strongly impaired in NKG2D(low) NK
cells. Reduction of NKG2D surface expression to 15%, corresponding to receptor
levels in resting NK cells, rendered cells fully insensitive to NKG2D triggering.
These data underscore the importance of NKG2D receptor cell surface density and
suggest a threshold of expression for optimal reactivity of human NK cells.
PMID- 17043027
TI - CD52 expression patterns in myeloma and the applicability of alemtuzumab therapy.
AB - Alemtuzumab has been proposed as a therapeutic agent in myeloma. CD52 was
detected on plasma cells in 46/106 patients but levels were 30-fold lower than on
alemtuzumab-responsive cells (n=138) and 8-fold lower than on alemtuzumab
resistant cells (n=57). The data suggest that myeloma plasma cells are unlikely
to be depleted by alemtuzumab in most patients.
PMID- 17043029
TI - Balancing within various discourses--the art of being old and living as a Sami
woman.
AB - The aim of this part of the Umea 85+ Study was to explore how indigenous women
narrate their lives and their experience of being old as Sami women. Interviews
with 9 old Sami women were analyzed using grounded theory. The categories
identified were "reindeer as the basis of life," "longing for significant Sami
values," "feeling valued as a Sami woman," and "changing for survival;" these
evolved into the core category: "balancing within various discourses-the art of
being old and living as a Sami woman." Knowing how to balance provided the
ability to make use of available opportunities.
PMID- 17043030
TI - Review: Takagi-Sugeno fuzzy modeling of skin permeability.
AB - The skin is a major exposure route for many potentially toxic chemicals. It is,
therefore, important to be able to predict the permeability of compounds through
skin under a variety of conditions. Available skin permeability databases are
often limited in scope and not conducive to developing effective models. This
sparseness and ambiguity of available data prompted the use of fuzzy set theory
to model and predict skin permeability. Using a previously published database
containing 140 compounds, a rule-based Takagi-Sugeno fuzzy model is shown to
predict skin permeability of compounds using octanol-water partition coefficient,
molecular weight, and temperature as inputs. Model performance was estimated
using a cross-validation approach. In addition, 10 data points were removed prior
to model development for additional testing with new data. The fuzzy model is
compared to a regression model for the same inputs using both R2 and root mean
square error measures. The quality of the fuzzy model is also compared with
previously published models. The statistical analysis demonstrates that the fuzzy
model performs better than the regression model with identical data and
validation protocols. The prediction quality for this model is similar to others
that were published. The fuzzy model provides insights on the relationships
between lipophilicity, molecular weight, and temperature on percutaneous
penetration. This model can be used as a tool for rapid determination of initial
estimates of skin permeability.
PMID- 17043032
TI - Subacute inhalation toxicity of 2-chloro-4-toluidine in rats.
AB - This article addresses results from a 4-wk inhalation exposure study in Wistar
rats with the vapor and/or aerosol atmospheres of 2-chloro-4-toluidine. Groups of
10 rats/sex were nose-only exposed to mean analytical concentrations of 19.1,
115.1, and 702.3 mg/m3 using an exposure regimen of 6 h/day and 20-22 exposures
within a time period of 4 wk. These concentrations were selected based on results
from a repeated 5 x 6 h/day pilot study using concentrations of 27.1, 104.8,
381.6, and 1283.7 mg/m3. In a single 4-h exposure study at the maximum tested
concentration of 7620 mg/m3, 1 of 10 female rats succumbed (no mortality in
males), while no mortality occurred at 3293 mg/m3. In the 1- and 4-wk studies
mortality occurred at 1283.7 and 702.3 mg/m3, respectively. Rats exposed for 4 wk
to 702.3 mg/m3 displayed characteristic signs of toxicity that included cyanosis,
respiratory distress, and significantly decreased body weights. Rectal
temperatures were significantly decreased at 115.1 mg/m3 and above. Dark and
enlarged spleens occurred at 702.3 mg/m3. At this concentration, prominent
treatment-related effects included methemoglobinemia, reticulocytosis, red blood
cells with Heinz bodies, decreased hemoglobin, hematocrit, and red blood cell
counts. Borderline evidence of erythrocytotoxicty was noticed at 115.1 mg/m3
(based on a minimal increase in Heinz bodies). Spleen and liver weights were
significantly increased at 702.3 mg/m3, whereas the thymus weight was decreased
at 115.1 mg/m3 and above. Microscopic changes were found in the spleen
(hemosiderosis) at 702.3 mg/m3. An atrophy of the olfactory epithelium in the
nasal cavities occurred at 115.1 mg/m3 and above. Clinical pathology revealed
changes pathognostic of hepatic effects, although microscopic examinations did
not reveal any specific changes. The no-observed-adverse-effect level (NOAEL) of
the 4-wk study was 19.1 mg/m3 and is based on the predominant atrophic changes of
the olfactory epithelium and the minimal to borderline erythrocytotoxic effects
at 115.1 mg/m3.
PMID- 17043031
TI - Brevetoxin-induced neural insult in the retrosplenial cortex of mouse brain.
AB - Brevetoxins (polyether breve toxins; PbTx) are polyether neurotoxins produced by
the marine dinoflagellate Karenia brevis, an organism associated with red tide
blooms in the Gulf of Mexico and along the Atlantic coast from Florida to North
Carolina. Brevetoxin-3 (PbTx-3) is a major component of the array of brevetoxins
found in marine aerosols measured along red tide affected beaches. Humans exposed
to aerosolized brevetoxins for short periods of time often suffer a variety of
adverse health effects. It was consequently of interest to assess the potential
for aerosolized brevetoxin to produce a neurotoxic response. Female BALB/c mice
were exposed nose-only for 2 consecutive days to PbTx-3 aerosol, with a 2-h
exposure on the first day and a 4-h exposure on the second day. The average PbTx
3 exposure concentrations on days 1 and 2 were 312 +/- 113 mug brevetoxin 3/m3
and 278 +/- 24 mug brevetoxin 3/m3, respectively. The brevetoxin-containing
aerosol had a mass median aerodynamic diameter of 0.92 mum with a geometric
standard deviation of 1.38. Coronal sections of mouse brains were evaluated for
neuronal damage using both silver and Fluoro-Jade B staining to identify
degenerating neuronal elements. PbTx-3 inhalation exposure produced neuronal
degeneration in the posterior cingulate/retrosplenial cortex of mice as evidenced
by silver-positive degenerating neurons in this region. No staining was found in
other regions of the PBTx-3-exposed mouse brains or in brains of control, sham
exposed mice. The existence of a neurotoxic insult in PbTx-3-exposed mice was
confirmed using Fluoro-Jade B to label degenerating neurons. Fluro-Jade-positive
neurons were observed in the retrosplenial cortex of PBTx-3 exposed, but not
control, mice. These results suggest that subacute exposure to PbTx-3 for 2 days
is sufficient to induce neuronal degeneration in a discrete region of the mouse
cerebral cortex.
PMID- 17043033
TI - Sampling period determination for heart rate logging under an exercise regimen.
AB - Using a mathematical procedure, we determine appropriate sampling rates for
logging heart rate, at a variety of exercise intensities. The mathematical
procedure involves correlating exercise and heart rate data to determine a
dynamical mathematical model, from which the frequency response of the
relationship between exercise intensity and heart rate can be determined. The
sampling rate is then straightforwardly deduced by making appropriate
measurements on the frequency response curve. We show how careful consideration
needs to be given to the choice of dynamical model structure and the work
regimen, so that consistent and convincing conclusions can be drawn. We
demonstrate that the dynamics of the work-rate/heart-rate system are dependent on
the nominal work/heart rate, but a 5-s sampling period, as used in many
commercial heart rate monitors, appears to be adequate, especially when some
averaging is performed before logging.
PMID- 17043034
TI - Ecological validity of neuropsychological assessment and perceived employability.
AB - Ecological validity studies that have examined the relationship between cognitive
abilities and employment in psychiatric and medical populations have found that a
wide range of cognitive domains predict employability, although memory and
executive skills appear to be the most important. However, no information is
available regarding a patient's self-perceived work attributes and objective
neuropsychological performance, and whether the same cognitive domains associated
with successful employment are also related to a patient's self-perception of
work competence. In the present study, 73 medical and psychiatric patients
underwent comprehensive neuropsychological assessment. Step-wise multiple
regression analyses revealed that the visual-spatial domain was the only
significant predictor of self-perceived work attributes and work competence as
measured by the Working Inventory (WI) and the Work Adjustment Inventory (WAI),
accounting for 7% to 10% of inventory score variability. The results raise the
intriguing possibility that targeting of visual spatial skills for remediation
and development might play a separate and unique role in the vocational
rehabilitation of a lower SES population, specifically, by leading to enhanced
self-perception of work competence as these individuals attempt to enter the job
market.
PMID- 17043035
TI - Idiopathic sudden hearing loss: contradictory clinical evidence, placebo effects
and high spontaneous recovery rate--where do we stand in assessing treatment
outcomes?
AB - Idiopathic sudden hearing loss (ISHL) has an estimated incidence of 10-20/100,000
per year, impairing not only patients' hearing but also their ability to interact
socially and their quality of life. Confronted with patients who demand
successful treatment, physicians need to judge potential treatment options with
regard to their reported efficiency, as well as their suitability for the
individual patient. The dilemma of assessing treatment outcomes and options in
ISHL will be discussed regarding a lack of knowledge of the disease's etiology,
contradictory clinical evidence, high spontaneous recovery rate, and possible
placebo effects. In conclusion, there is a dearth of structured research adhering
to a common protocol, which makes comparison of trials and assessment of
potential treatment outcomes difficult. Further research is warranted, taking
some key recommendations into consideration.
PMID- 17043037
TI - Seasonal variation of falling asleep while driving: An examination of fatal road
accidents.
AB - Road accidents related to sleep show a clear time-of-day pattern. Following the
previous finding that such accidents in Finland happen more often (absolutely and
relatively) during the summer months, especially during the afternoon, the main
aim of this study was to reveal the factors behind such seasonality. The data
included the computerized database of the Finnish fatal road accident
investigation system restricted to nonprofessional, non-intoxicated car drivers
(N=1464) and sample of the original folders (N=101). The results of the analysis
on the sample of the original folders showed that investigation teams adequately
documented and explained their decisions concerning falling-asleep accidents and
that the observed seasonality is a real phenomenon, not a result of bias of the
teams. With the exception of 26-35-year-olds, men of all of the other age groups
had a notable absolute and relative increase of sleep-related accidents in the
summer. Young male drivers (< or =25 yrs), followed by the oldest group (> or =66
yrs) had the highest increase in the absolute number of sleep-related accidents
between the summer and winter months, while the relative change was the highest
for ages 56-65. Women showed similar trends. A detailed analysis of 44 cases of
summer afternoon falling-asleep accidents revealed that many drivers were engaged
in unusual activities the day or night before the accident. The findings are
discussed in relation to different driving and lifestyle habits between seasons,
including sleep quality. Preliminary results of this study were presented at the
17th Congress of the European Sleep Research Society, Prague 2004.
PMID- 17043038
TI - Cross-sectional reference values for height, weight and body mass index of school
children living in Tehran, Iran.
AB - AIM: The aim of the study was to create reference values for weight, height and
body mass index (BMI) of school children living in Tehran. METHOD AND SAMPLES:
The study subjects consisted of 1,420 girls between 6 and 17 years of age and
1,515 boys between 6 and 15 years of age. Samples were collected by a multistage
sampling method from schools in different areas of Tehran. All participants were
established to be healthy and their height, weight and BMI evaluated. Reference
standard values estimated by the LMS method using LMS Light software and 3rd,
5th, 10th, 25th, 50th, 75th, 90th, 97th and 85th (only for BMI) centiles were
constructed and the results compared with US reference values. RESULTS: The
centiles provided a good fit to the data. In boys, there were some significant
differences of mean standard deviation scores (SDS) of height and BMI from zero,
but there were no significant differences in weight. In girls, the mean SDS of
height, weight and BMI were significantly lower than zero, especially for 7-9
years of age. Among 12-13-year-old girls, the mean SDS of height, weight and BMI
came closer to zero, and the differences were not significant. Thereafter,
although girls seemed to be shorter than US reference measures, their weight and
BMI did not differ from reference values significantly. CONCLUSION: Our results
for boys between 6 and 15 years are comparable with US reference values; however,
the US reference values, especially for height, are not applicable for Iranian
girls between 6 and 17 years.
PMID- 17043039
TI - Present and future biochemical markers for detection of acute coronary syndrome.
AB - The use of biochemical markers in the diagnosis and management of patients with
acute coronary syndrome has increased continually in recent decades. The
development of highly sensitive and cardiac-specific troponin assays has changed
the view on diagnosis of myocardial infarction and also extended the role of
biochemical markers of necrosis into risk stratification and guidance for
treatment. The consensus definition of myocardial infarction places increased
emphasis on cardiac marker testing, with cardiac troponin replacing creatine
kinase MB as the "gold standard" for diagnosis of myocardial infarction. Along
with advances in the use of more cardiac-specific markers of myocardial necrosis,
biochemical markers that are involved in the progression of atherosclerotic
plaques to the vulnerable state or that signal the presence of vulnerable plaques
have recently been identified. These markers have variable abilities to predict
the risk of an individual for acute coronary syndrome. The aim of this review is
to provide an overview of the well-established markers of myocardial necrosis,
with a special focus on cardiac troponin I, together with a summary of some of
the potential future markers of inflammation, plaque instability, and ischemia.
PMID- 17043040
TI - Influence of particle size on drug delivery to rat alveolar macrophages following
pulmonary administration of ciprofloxacin incorporated into liposomes.
AB - In order to confirm the efficacy of ciprofloxacin (CPFX) incorporated into
liposomes (CPFX-liposomes) for treatment of respiratory intracellular parasite
infections, the influence of particle size on drug delivery to rat alveolar
macrophages (AMs) following pulmonary administration of CPFX-liposomes was
investigated. CPFX-liposomes were prepared with hydrogenated soybean
phosphatidylcholine (HSPC), cholesterol (CH) and dicetylphosphate (DCP) in a
lipid molar ratio of 7/2/1 by the hydration method and then adjusted to five
different particle sizes (100, 200, 400, 1000 and 2000 nm). In the
pharmacokinetic experiment, the delivery efficiency of CPFX to rat AMs following
pulmonary administration of CPFX-liposomes increased with the increase in the
particle size over the range 100-1000 nm and became constant at over 1000 nm. The
concentrations of CPFX in rat AMs until 24 h after pulmonary administration of
CPFX-liposomes with a particle size of 1000 nm were higher than the minimum
inhibitory concentration of CPFX against various intracellular parasites. In a
cytotoxic test, no release of lactate dehydrogenase (LDH) from rat lung tissues
by pulmonary administration of CPFX-liposomes with a particle size of 1000 nm was
observed. These findings indicate that efficient delivery of CPFX to AMs by CPFX
liposomes with a particle size of 1000 nm induces an excellent antibacterial
effect without any cytotoxic effects on lung tissues. Therefore, CPFX-liposomes
may be useful in the development of drug delivery systems for the treatment of
respiratory infections caused by intracellular parasites, such as Mycobacterium
tuberculosis, Chlamydia pneumoniae and Listeria monocytogenes.
PMID- 17043042
TI - Role of TNFRp55 in Yersinia enterocolitica O:3-induced arthritis: triggering
bacterial antigens and articular immune response.
AB - OBJECTIVES: The pathogenesis of reactive arthritis (ReA), an aseptic synovitis
that follows an extra-articular infection, is incompletely known. We studied the
impact of tumour necrosis factor receptor (TNFR) p55 deficiency on the
progression to ReA after oral Yersinia enterocolitica O:3 infection, the Yersinia
antigens triggering articular inflammation and a possible articular TNFRp55
mediated mechanism that protects against ReA. METHODS: Wild-type C57BL/6 and
TNFRp55-/- mice were orogastrically infected with Y. enterocolitica O:3 and
monitored for survival and arthritis development. The bacterial load was
determined in mesenteric lymph nodes (MLNs), the spleen and joints. Interferon
(IFN)-gamma, TNF-alpha and IL-10 mRNA expression in MLN and joints were analysed
by reverse transcription-polymerase chain reaction (RT-PCR). Articular antibodies
to Yersinia antigens, TNF-alpha protein and nitric oxide (NO) levels were
assessed. Acute arthritis was evaluated after joint injection of Yersinia
antigens. RESULTS: The survival rate was 60% in TNFRp55-/- mice. They showed
impaired bacterial clearance in MLN, the spleen and joints, and excessive mRNA
expression of pro-inflammatory cytokines in MLN. Clinical and histological
examinations revealed that TNFRp55-/- mice developed severe arthritis. Moreover,
augmented articular outer membrane protein (OMP)-specific antibodies and TNF
alpha but impaired NO levels were detected in TNFRp55-/- mice. Synovial
inflammatory response was detected by joint OMP injection. CONCLUSIONS: TNFRp55
mediated immune mechanisms prevent ReA development after oral infection with Y.
enterocolitica O:3. Yersinia OMPs are the relevant antigens triggering ReA. NO
induction through TNFRp55 signalling could have a local antibacterial function to
prevent ReA. This study could contribute to ReA-specific therapeutic studies.
PMID- 17043043
TI - Traditional cardiovascular risk factors in primary Sjogren's syndrome--role of
dyslipidaemia.
PMID- 17043046
TI - Patient perception of UK scleroderma services--results of an anonymous
questionnaire.
PMID- 17043045
TI - A longitudinal study exploring pain control, treatment and service provision for
individuals with end-stage lower limb osteoarthritis.
AB - OBJECTIVE: To investigate the level of pain control, treatment and service
provision amongst individuals with end-stage lower limb osteoarthritis who were
on the waiting list for hip or knee joint replacement. METHODS: A total of 105
patients on a waiting list for primary knee or hip replacement from a regional
orthopaedic centre in the UK were recruited. The study was longitudinal and based
on direct interviews at baseline and 6 months, with a postal questionnaire at 3
months. Data were collected on pain by a visual analogue scale (VAS) and the
Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. In
addition, medication and the use of services and treatments were recorded.
RESULTS: Participants experienced high levels of pain as measured by VAS [mean
7.0; 95% confidence interval (CI) 6.6-7.5] and WOMAC pain (mean 11.2; 95% CI 10.6
11.9). The majority of participants (78, 74%) was taking analgesics more than
once a day. Primary care utilization was variable. Of the 74 (70%) participants
who had consulted their GP in the previous 3 months, 41 (55%) had not discussed
their pain or osteoarthritis during these consultations. Just below one-third of
participants (31, 30%) reported to have received information on osteoarthritis.
CONCLUSIONS: Pain appears to be difficult to manage in individuals with end-stage
lower limb osteoarthritis. Individuals appeared not to be taking appropriate
levels of analgesia in relation to levels of pain. Improvements are required in
the provision of information on pain and osteoarthritis. Patients would benefit
from more proactive management by health professionals (especially by GPs).
PMID- 17043047
TI - Investigation of the role of ENPP1 and TNAP genes in chondrocalcinosis.
AB - OBJECTIVES: Extracellular inorganic pyrophosphate (ePPi) inhibits certain forms
of pathological mineralization while promoting others. Three molecules involved
in ePPi regulation are important candidates for the development of calcium
pyrophosphate dihydrate chondrocalcinosis (CPPD CC). These include ANKH,
ectonucleotide pyrophosphatase (ENPP1) and TNAP. We have previously showed that
genetic variation in ANKH is a cause of autosomal dominant familial CC and also
some sporadic cases of CPPD CC. We now investigate the possible role of ENPP1 and
TNAP in CPPD CC. METHODS: Exons, untranslated regions (UTR) and exon-intron
boundaries of ENPP1 and TNAP were sequenced using ABI Big Dye chemistry on
automated sequencers. Sixteen variants were identified (3 in ENPP1 and 13 in
TNAP) and were subsequently genotyped in 128 sporadic Caucasian CPPD CC patients
and 600 healthy controls using a combination of polymerase chain
reaction/restriction fragment-length polymorphism analysis or using Taqman.
Allele and genotype frequencies were compared between cases and controls using
the chi(2) test. Linkage disequilibrium, haplotype and the single nucleotide
polymorphism-specific analyses were also performed. This study had 80% power to
detect an odds ratio of 2.2 or more at these loci. RESULTS: No difference was
observed in the allele or genotype frequencies between patients and controls at
either ENPP1 or TNAP. CONCLUSIONS: Polymorphisms of ENPP1 and TNAP are not major
determinants of susceptibility to CC in the population studied. Further studies
of the aetiology of sporadic CPPD CC are required to determine its causes.
PMID- 17043048
TI - The differential expression of corticosteroid receptor isoforms in corticosteroid
resistant and -sensitive patients with rheumatoid arthritis.
AB - OBJECTIVE: A proportion of patients with rheumatoid arthritis (RA) fail to
respond adequately to corticosteroid (CS) therapy. Using an in vitro CS
sensitivity bioassay, we have subdivided RA patients into steroid-sensitive (SS)
and -resistant (SR) subgroups and this correlates with clinical responses to CS
therapy. CSs exert their effects via the CS receptor (CR), which exists as two
main isoforms, CRalpha and CRbeta. CRbeta can function as a negative inhibitor of
CRalpha. We have hypothesized that steroid resistance in RA patients is due in
part to a relative over-expression of the CRbeta. METHODS: Peripheral blood
mononuclear cells (PBMCs) were isolated from SS and SR RA patients. CRalpha and
CRbeta mRNA expression was determined by quantitative real time polymerase chain
reaction (qRT-PCR). The ratio of CRbeta/CRalpha mRNA expression was determined.
CRalpha and CRbeta protein expression by PBMCs was analysed by flow cytometry.
RESULTS: qRT-PCR analysis showed a trend towards higher expression of both CRbeta
and basal CRbeta/CRalpha ratio in SR RA patients. Stimulation of PBMCs in vitro
with concanavalin-A induced a significantly higher CRbeta mRNA expression, and
CRbeta/CRalpha ratio in SR RA patients compared with SS patients, which was not
inhibited by hydrocortisone. Flow cytometry showed that the percentage of PBMCs
staining for CRbeta protein was significantly lower in the SS RA group (SS 43.3
+/- 14.8% vs SR 88.6 +/- 8.6%; P < 0.0010). The mean intensity of fluorescence
CRbeta staining was higher in the SR RA patients (P < 0.001). CONCLUSION: We show
for the first time that CRbeta is over-expressed in SR RA patients and that
hydrocortisone fails to inhibit concanavalin-A stimulated increase in CRbeta mRNA
in SR RA patients. This mechanism may contribute in part to the CS
hyporesponsiveness seen in some RA patients.
PMID- 17043049
TI - Very early 'Rheumatoid' arthritis cohorts: limited by selection.
PMID- 17043050
TI - Engagement and satisfaction with an Internet-based physical activity intervention
in patients with rheumatoid arthritis.
AB - OBJECTIVE: To assess the engagement in and satisfaction with an Internet-mediated
physical activity intervention with individual supervision in patients with
rheumatoid arthritis (RA). METHODS: The intervention studied was one of the two
strategies aimed at enhancing physical activity in RA patients that were being
compared in a randomized controlled trial. A total of 82 patients, all
experienced in using Internet and e-mail and registered at three different
rheumatology out-patient clinics, were randomly allocated to the Internet
mediated individualized intervention (52 weeks). They had access to personal
physical activity schedules and received individual supervision by a physical
therapist by means of weekly e-mail feedback. In addition, telephone contacts, an
online discussion forum, six face-to-face group meetings and electronic
newsletters were offered. Besides registration of returned physical activity
schedules, engagement and satisfaction were measured through questionnaires.
RESULTS: The median physical activity schedule return rate of the 82 participants
was 55%. The mean number of patients logging into the website at least once a
week was 53 (70%) over 12 months. Of all patients, 69 returned the questionnaires
(response 84%). Telephone contacts were used by 38/67 patients (57%), the mean
(SD) number of attended group meetings was 3.1 (1.5) and the discussion forum
comprised 15 posted messages. Overall, the proportions of patients being (very)
satisfied with the amount of e-mail contacts, telephone contacts, usefulness of
website information, physical activity schedules, group meetings and website
layout were >/=85%. A smaller proportion of patients were satisfied with the
links to other websites (68%), the newsletters (55%) and the online discussion
forum (32%). CONCLUSION: Physical activity schedules with weekly feedback by e
mail, telephone contacts and a limited number of group meetings were frequently
used website tools and modes of communication of an Internet-based physical
activity intervention, with high-satisfaction rates from RA patients. Discussion
forum and newsletters were less used and appreciated. Caution should be taken
when extrapolating the results found to groups of patients who are not
experienced Internet and e-mail users or patients with more severe physical
disabilities.
PMID- 17043051
TI - Invasive fungal infection in systemic lupus erythematosus: an analysis of 15
cases and a literature review.
AB - OBJECTIVE: To analyse 15 cases of invasive fungal infection and mortality
parameters in the largest series in the last 35 yrs of patients with systemic
lupus erythematosus (SLE) at a single medical centre. METHODS: Fifteen patients
with SLE and invasive fungal infections were retrospectively enrolled. Clinical
and laboratory data, fungal species and infected sites, corticosteroid and
immunosuppressant doses and SLE disease activity index were assessed
retrospectively. Comparison and correlation analyses utilized Fisher's exact
test, the chi-square test, Mann-Whitney U-test or the Wilcoxon signed-rank test
where appropriate. RESULTS: In contrast to other review reports, Cryptococcus
neoformans was the most commonly identified fungus in this Taiwanese series.
Notably, the prevalence of autoimmune haemolytic anaemia and positive results for
the anti-cardiolipin antibody in this study were significantly higher than those
in SLE patients in general (P < 0.0001 and P < 0.0001, respectively). Fungal
infection contributed to cause of death in 7 of 15 (46.7%) patients, of which
Cryptococcus neoformans accounted for six of these infections. Low-dose
prednisolone (<1 or <0.5 mg/kg/day based on arbitrary division) prior to fungal
infection tended to correlate with 1 yr mortality after diagnosis of SLE (P =
0.077 or P = 0.080). However, following fungal infection, patients who died from
infection itself had been prescribed with higher prednisolone dose or equivalent
than surviving patients (P = 0.016). All SLE patients with fungal infections had
active SLE (SLEDAI >7). CONCLUSIONS: Cryptococcus neoformans infection accounted
for most fatalities in SLE patients with fungal infections in this series. Active
lupus disease is probably a risk factor for fungal infection in SLE patients.
Notably, low prednisolone doses prior to fungal infection or high prednisolone
doses following fungal infection tended to associate with or correlated to
fatality, respectively. Therefore, we suggest that different prednisolone doses
prescribed at various times impact the incidence of fungal infection and its
associated mortality.
PMID- 17043052
TI - Atorvastatine for chronic synovitis due to massive intra-articular cholesterol
monohydrate deposition in long-standing rheumatoid arthritis.
PMID- 17043053
TI - Takayasu's arteritis--recent advances in imaging offer promise.
AB - Takayasu's arteritis (TA), a rare large vessel vasculitis of unknown aetiology,
remains a difficult disease to manage with diagnosis often delayed until the late
occlusive stage when irreversible vascular damage has occurred. Recent studies
suggest that non-invasive imaging modalities including magnetic resonance
imaging, ultrasound and 18F-fluorodeoxyglucose positron emission tomography (18F
FDG-PET) allow diagnosis of TA earlier in the disease course than standard
angiography and provide a means for monitoring disease activity. Choice of
appropriate therapy for TA is limited by a lack of evidence and a combination of
corticosteroids and immunosuppressive drugs is most commonly used. Novel
therapeutic approaches such as the use of anti-tumour necrosis factor alpha (TNF
alpha) inhibitors and drug-eluting arterial stents show promise for improving the
prognosis in severe disease. In addition, strict management of traditional
cardiovascular risk factors such as dyslipidaemia, hypertension and lifestyle
factors is mandatory to minimize secondary cardiovascular complications, which
are the major cause of death in this disease.
PMID- 17043054
TI - Mass spectrometric mapping of linker histone H1 variants reveals multiple
acetylations, methylations, and phosphorylation as well as differences between
cell culture and tissue.
AB - Posttranslational modifications of histones are involved in regulation of
chromatin structure and gene activity. Whereas the modifications of the core
histones H2A, H2B, H3, and H4 have been extensively studied, our knowledge of H1
modifications remained mainly limited to its phosphorylation. Here we analyzed
the composition of histone H1 variants and their modifications in two human cell
lines and nine mouse tissues. Use of a hybrid linear ion trap-orbitrap mass
spectrometer facilitated assignment of modifications by high resolution and low
ppm mass accuracy for both the precursor and product mass spectra. Across
different tissues we identified a range of phosphorylation, acetylation, and
methylation sites. We also mapped sites of ubiquitination and report
identification of formylated lysine residues. Interestingly many of the mapped
modifications are located within the globular domain of the histones at sites
that are thought to be involved in binding to nucleosomal DNA. Investigation of
mouse tissue in addition to cell lines uncovered a number of interesting
differences. For example, whereas methylation sites are frequent in tissues, this
type of modification was much less abundant in cultured cells and escaped
detection. Our study significantly extends the known spectrum of linker histone
variability.
PMID- 17043055
TI - The results of cosmic radiation in-flight TEPC measurements during the CAATER
flight campaign and comparison with simulation.
AB - The European-Commission-supported project DOSMAX (Dosimetry of Aircrew Exposure
to Radiation During Solar Maximum) was aimed at measuring aircrew exposure to
cosmic radiation on-board the aircraft during solar maximum. During a dedicated
international comparison mission (Co-ordinated Access to Aircraft for
Transnational Environmental Research; CAATER) different measurement techniques
have been compared by six European institutes (Results of the CAATER Mission,
DOSMAX Meeting, Dublin, June 2004). In this paper, we present the tissue
equivalent proportional counter (TEPC) measurements carried out by ARC
Seibersdorf research (ARCS), Austria, and Institut de Radioprotection et de
Surete Nucleaire (IRSN), France, together with a comparison with simulation
results under the same conditions. The whole flight campaign consists of four
different in-flight investigations performed at two different geographical
positions at 12.2 km (FL 400) and 9.8 km (FL 320). One location was chosen above
Rome (42 degrees North, 12 degrees East), Italy, for high cut-off rigidity (6.4
GV) and the second above Aalborg (57 degrees North, 10 degrees East), Denmark,
for low cut-off rigidity (1.8 GV). The TEPC measurements are presented in terms
of absorbed dose and ambient dose equivalent as well as microdosimetric spectra
as a function of lineal energy. For the same conditions of the CAATER flights the
response of the TEPC has also been simulated by using the Monte Carlo Transport
Code FLUKA (version 2003). The results from simulations are compared with
measurements and they show a reasonable agreement.
PMID- 17043056
TI - Negative selection with the Diphtheria toxin A fragment gene improves frequency
of Cre-mediated cassette exchange in ES cells.
AB - The Cre-lox system is an important tool for genetic manipulation in embryonic
stem cells. We previously reported that the cassette exchange strategy using the
mutant lox66/71 and lox2272 combination showed high recombination efficiency and
stability. However, the efficiency was strongly affected by the position of
chromosomal target lox sites. To enrich successful cassette exchange events, even
in clones showing lower recombination efficiency, we have improved exchange
vector. The Diphtheria toxin A fragment gene was placed in the un-exchanged
region for negative selection and the puromycin N-acetyltransferase gene, instead
of the neomycin phosphotransferase gene, was used for positive selection. By
reducing random integration, the frequency of successful cassette exchange
increased up to 2-4 fold. Furthermore, by adding the third lox site to induce
intrarmolecular recombination, the recombination efficiency of cassette exchange
itself was improved, and the frequency increased to maximum 5 fold, in which the
percentage of exchanged clones reached to 50-70%. This strategy should be useful
for other recombinase-mediated cassette exchanges.
PMID- 17043057
TI - PTEN c.511C>T nonsense mutation in a BRRS family disrupts a potential exonic
splicing enhancer and causes exon skipping.
AB - Bannayan-Riley-Ruvalcaba syndrome (BRRS) is an autosomal dominant disorder
characterized by macrocephaly, intestinal hamartomatous polyps, lipomas and
pigmented macules of the glans penis. We identified a Thai family affected with
BRRS. In addition to typical manifestations of BRRS, the proband has a large
hepatic AVM which is rarely found in BRRS. The molecular analysis revealed
affected members were heterozygous for an exon skipping-associated nonsense
mutation c.511C>T in the PTEN gene. The mutation was previously assumed to be
deleterious by causing a change to a termination codon, Q171X. We, herein, found
that another pathogenic effect was splicing related by disrupting a potential
exonic splicing enhancer (ESE) and causing an entire exon 6 skipping. The results
prompted us to investigate other reported missense/nonsense mutations in the PTEN
gene. We found that they do not colocalize with ESE sites, suggesting that most
of their pathogenic effects are not through ESE disruption.
PMID- 17043058
TI - The range of tumor extension should have precedence over the location of the
deepest tumor center in determining the regional lymph node grouping for widely
extending esophageal carcinomas.
AB - BACKGROUND: The Japanese Guide Lines for the Clinical and Pathologic Studies on
Carcinoma of the Esophagus (9th edn) give precedence to the location of the
deepest tumor center rather than the range of tumor extension when determining
regional lymph node grouping. We evaluated the validity of this recommendation.
METHODS: The subjects were 49 patients with carcinomas of the distal thoracic
esophagus and cardia who had undergone esophagectomy with three-field lymph node
dissection. We measured variables defining tumor location, such as the distance
from the esophagogastric junction (EGJ) to the proximal margin of the tumor
(DJP), the distance from the EGJ to the distal margin of the tumor (DJD), and the
distance from the EGJ to the deepest tumor center (DJC). To examine the relation
of tumor location to lymph node metastasis in the proximal direction, the
patients were divided into two groups according to the presence (14 patients) or
absence (35 patients) of middle-upper mediastinal and/or cervical lymph node
metastases. These two groups were compared with respect to the above variables.
To analyze lymph node metastasis in the distal direction, the patients were also
divided into two groups according to the presence (12 patients) or absence (37
patients) of distant abdominal lymph node metastases. These two groups were
similarly compared with respect to the above variables. RESULTS: DJP was
significantly longer in the patients with middle-upper mediastinal and/or
cervical lymph node metastases than in those without such metastases. Multiple
logistic regression analysis showed that the DJP was a better predictor of middle
upper mediastinal and/or cervical lymph node metastases than was the DJC. The DJD
was significantly longer in the patients with distant abdominal lymph node
metastases. Multiple logistic regression analysis also showed that the DJD was a
better predictor of distant abdominal lymph node metastases than was the DJC.
CONCLUSIONS: The range of tumor extension is a more reliable predictor of the
risk of distant lymph node metastases than is the location of the deepest tumor
center in esophageal carcinoma.
PMID- 17043059
TI - A phase II trial of docetaxel plus capecitabine in patients with previously
treated non-small cell lung cancer.
AB - BACKGROUND: A combination of docetaxel (T) and capecitabine (X) showed
synergistic effects in preclinical studies and phase III randomized trials of
metastatic breast cancer. We conducted this phase II study to examine its
efficacy in previously treated non-small cell lung cancer (NSCLC) patients.
METHODS: Patient eligibility required advanced NSCLC with measurable lesion(s),
at least one prior regimen failure and Eastern Cooperative Oncology Group (ECOG)
performance status 0-2. Treatment consisted of T 36 mg/m(2) i.v. on days 1 and 8
plus X 1000 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle (level I) or T 30
mg/m(2) i.v. on days 1 and 8 plus X 625 mg/m(2) p.o. b.i.d. on days 1-14 of a 21
day cycle (level II). RESULTS: A total of 35 patients (M/F=24/11) were enrolled;
29 had received one prior regimen and 19 had received platinum-based regimens.
Significant non-hematologic toxicities were observed after the treatment given at
level I, including one treatment-related death. Subsequently 29 patients were
treated at level II. The treatment at level II was well tolerated with grade 3 or
4 neutropenia only in 10%, grade 3 asthenia in 21% and stomatitis in 14% of
patients. Four (15%) of 27 evaluable patients had partial response (PR) at level
II and eight (30%) had stable disease (SD). CONCLUSIONS: The TX regimen showed
modest antitumor effects in patients with previously treated NSCLC. For further
studies, we recommend T 30 mg/m(2) i.v. on days 1 and 8 plus X 625 mg/m(2) p.o.
b.i.d. on days 1-14 of a 21-day cycle.
PMID- 17043060
TI - Effect of clopidogrel on 1-year mortality in hospital survivors of acute ST
segment elevation myocardial infarction in clinical practice.
AB - AIMS: We sought to assess the effect of clopidogrel on clinical events 1 year
after discharge in survivors of ST-elevation myocardial infarction (STEMI) in
clinical practice. METHODS AND RESULTS: We analysed data of consecutive survivors
of acute STEMI and either concomitant therapy with aspirin or aspirin plus
clopidogrel at discharge, who were prospectively enrolled in the Acute Coronary
Syndromes (ACOS) registry between July 2000 and November 2002. A total of 5886
(3795 with and 2091 without clopidogrel) patients were included into this
analysis. Patients were divided into three groups according to the initial
reperfusion therapy: no reperfusion therapy (n=1445), fibrinolysis (n=1734), or
primary PCI (n=2707). The multivariable analysis for 12+2 month mortality after
discharge using the propenstiy score with adjustment for baseline characteristics
and treatments (age, sex, diabetes mellitus, hypertension, prior MI,
hyperlipidaemia, renal insufficiency, cardiogenic shock, heart rate, systolic
blood pressure, anterior infarct location, reduced left ventricular function,
elective revascularization, beta-blockers, statins, ACE-inhibitors) showed that
mortality was significantly lower in the aspirin plus clopidogrel group compared
with the aspirin group in the total group and patients with reperfusion therapy
[total group odds ratio (OR) 0.48, 95% confidence interval (CI) 0.48-0.61; no
reperfusion therapy OR 0.96, 95% CI 0.65-1.45; fibrinolysis OR 0.53, 95% CI 0.32
0.87; primary percutaneous coronary intervention OR 0.38, 95% CI 0.23-0.62].
CONCLUSION: In clinical practice, adjunctive therapy with clopidogrel, in
addition to aspirin, in survivors after STEMI is associated with a reduction in 1
year mortality in patients treated with early reperfusion therapy.
PMID- 17043061
TI - Soccer world championship: a challenge for the cardiologist.
AB - The 18th FIFA Soccer World Cup 2006 in Germany enthused millions of people
worldwide, but only little is known about the association of such an event with
cardiovascular events. Modest physical activity is known to reduce the
cardiovascular risk significantly. On the other hand, vigorous physical activity
and emotional strain increase the cardiovascular risk and the incidence of
cardiovascular events likely due to an increased sympathetic tone with
consecutive catecholamine stimulation of the heart. Few reviews and case-reports
are dealing with the risk of physical activity in cardiovascular high-risk
patients or athletes with congenital heart diseases (e.g. hypertrophic
obstructive cardiomyopathy), but the impact of highly competitive events on
cardiovascular events, especially in spectators were rarely addressed. Thus, the
increased risk of cardiovascular events in players and spectators were addressed
in this review with respect to various soccer matches and tournaments, such as
the FIFA World Cup.
PMID- 17043062
TI - 'Cobra malformation' of an Amplatzer device during percutaneous closure of a
ventricular septal defect.
PMID- 17043063
TI - Gigantic left atrial thrombus.
PMID- 17043064
TI - Functional mitral regurgitation in acute coronary syndrome: what determines its
prognostic impact?
PMID- 17043065
TI - Australian parents' views on their 5-6-year-old children's food choices.
AB - The home food environment is central to the development of healthy eating
behaviours, but associations between the home food environment and children's
food choices are not yet fully understood. The aims of this study were to explore
parents' views regarding factors that influence children's food choices and
parents' decision-making regarding the food they provide to their children. In
depth one-on-one interviews were conducted using a semi-structured interview
schedule. Key concepts and themes were coded independently by two investigators.
Participants include seventeen parents (16 mothers and 1 father) of children in
their first year of formal schooling (aged 5-6 years). Five main themes emerged
from the interviews: food marketing, food availability/food exposure, feeding
strategies, modelling of eating and opportunities for food involvement. Parents
believed that food marketing influenced their child's food preferences but
differed in the ways they managed these influences. The food made available to
children was also seen to influence what a child ate. Yet, although some parents
believed it was the parents' role to determine what foods were made available to
their child, others offered food on the basis of the child's tastes or
preferences. The use of food as a reward was a feeding strategy employed by many
parents. Family mealtimes were seen as an important opportunity for modelling of
eating behaviour by parents. Peers were also seen to influence children's food
preferences and eating behaviour. Finally, many parents believed that involving
children in the preparation of food had a positive impact on children's food
choices. Associations between the home food environment and children's food
choices are complex and involve multiple mediators. Parents' views on the
promoters and reinforcers of their decision-making regarding food and their
child's food choices provide useful insights into these mediating factors.
Increased understanding of these relationships is likely to enhance obesity
prevention efforts.
PMID- 17043066
TI - P-selectin mediates metastatic progression through binding to sulfatides on tumor
cells.
AB - Hematogenous carcinoma metastasis is associated with tumor cell emboli formation,
which is now known to be facilitated by selectins. P-selectin-mediated
interactions of platelets with cancer cells are based mostly on mucin- and
glycosaminoglycan-type selectin ligands. We previously showed that mouse colon
carcinoma cells (MC-38) carry P-selectin ligands of nonmucin origin, which were
not identified. Here we show that P-selectin ligands recognized on MC-38 cells
are sulfated glycolipids, thereby facilitating experimental metastasis in a
syngeneic mouse model. Metabolic inhibition of sulfation by incubation of cells
with sodium chlorate almost completely abrogated P-selectin binding. Metabolic
labeling of MC-38 cells with (35)S sulfate revealed only a single band as
detected by high-performance thin layer chromatography analysis of a total lipid
extract. Matrix-assisted laser desorption/ionization tandem time-of-flight/time
of-flight analysis (MALDI-TOF-TOF) analysis of the purified sulfate-containing
lipid fraction identified the selectin ligand to be a sulfated galactosylceramide
SM4 (HSO(3)-3Galbeta-1Cer). Modulation of glycolipid biosynthesis in MC-38 cells
altered P-selectin binding, thereby confirming sulfoglycolipids to be major P
selectin ligands. In addition, P-selectin was also found to recognize
lactosylceramide sulfate SM3 (HSO(3)-3Galbeta-4Glcbeta-1Cer) and
gangliotriaosylceramide sulfate SM2 [GalNAcbeta-4(HSO(3)-3)Galbeta-4Glcbeta-1Cer]
in human hepatoma cells. Finally, the enzymatic removal of sulfation from the
cell surface of MC-38 cells resulted in decreased P-selectin binding and led to
attenuation of metastasis. Thus, SM4 sulfatide serves as a native ligand for P
selectin contributing to cell-cell interactions and to facilitation of
metastasis.
PMID- 17043067
TI - Analysis of surface electrocardiograms in atrial fibrillation: techniques,
research, and clinical applications.
AB - Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical
practice. Neither the natural history of AF nor its response to therapy is
sufficiently predictable by clinical and echocardiographic parameters. The
purpose of this article is to describe technical aspects of novel
electrocardiogram (ECG) analysis techniques and to present research and clinical
applications of these methods for characterization of both the fibrillatory
process and the ventricular response during AF. Atrial fibrillatory frequency (or
rate) can reliably be assessed from the surface ECG using digital signal
processing (extraction of atrial signals and spectral analysis). This measurement
shows large inter-individual variability and correlates well with intra-atrial
cycle length, a parameter which appears to have primary importance in AF
maintenance and response to therapy. AF with a low fibrillatory rate is more
likely to terminate spontaneously and responds better to antiarrhythmic drugs or
cardioversion, whereas high-rate AF is more often persistent and refractory to
therapy. Ventricular responses during AF can be characterized by a variety of
methods, which include analysis of heart rate variability, RR-interval
histograms, Lorenz plots, and non-linear dynamics. These methods have all shown a
certain degree of usefulness, either in scientific explorations of
atrioventricular (AV) nodal function or in selected clinical questions such as
predicting response to drugs, cardioversion, or AV nodal modification. The role
of the autonomic nervous system for AF sustenance and termination, as well as for
ventricular rate responses, can be explored by different ECG analysis methods. In
conclusion, non-invasive characterization of atrial fibrillatory activity and
ventricular response can be performed from the surface ECG in AF patients.
Different signal processing techniques have been suggested for identification of
underlying AF pathomechanisms and prediction of therapy efficacy.
PMID- 17043068
TI - The assessment of autonomic function in chronic atrial fibrillation: description
of a non-invasive technique based on circadian rhythm of atrioventricular nodal
functional refractory periods.
AB - AIMS: Heart rate variability (HRV) parameters can be used to assess autonomic
function and to predict outcome, but this has been done exclusively in patients
with sinus rhythm. Atrial fibrillation (AF) is the commonest sustained arrhythmia
and is particularly prevalent in heart failure. We have developed a simple index
to assess autonomic function in patients with chronic AF. METHODS AND RESULTS:
Forty patients with chronic AF (>1 month) and symptoms of heart failure underwent
ambulatory 24 h electrocardiography recording as well as evaluation of symptoms,
exercise capacity (6 min walk distance), ventricular function (echocardiography
and radionuclide ventriculography), and neuroendocrine activation. A number of
standard HRV parameters shown to have prognostic significance in sinus rhythm
were also determined. A modified in-house HRV statistical programme was used to
filter labelled QRS intervals and to compute the 5th percentile RR interval in
each hour. This parameter has been shown to approximate the functional refractory
period (FRP) of the atrioventricular node (AVN). A cosine curve was fitted to
hourly 5th percentile RR intervals for each patient and from this was estimated
the diurnal change in hourly 5th percentile RR interval (approximating DeltaFRP
of the AVN) and, by inference, diurnal variation in sympathovagal input to the
AVN. Digoxin was the sole agent permitted for control of ventricular rate.
DeltaFRP of the AVN varied and revealed a significant correlation, on
multivariate analysis, with mean RR interval (P<0.001), SDARR (SD of 5-min
average RR intervals during 24 h, P<0.001), and NYHA class of heart failure
(classes III and IV heart failure vs. classes I and II, P=0.02). SDARR has
previously been shown independently to predict mortality in patients with chronic
AF and heart failure. CONCLUSION: This analysis describes a novel non-invasive
method for assessing autonomic function in chronic AF. Whether DeltaFRP in
chronic AF patients can independently predict adverse prognosis or sudden death
requires further study.
PMID- 17043069
TI - Verification of pacemaker automatic mode switching for the detection of atrial
fibrillation and atrial tachycardia with Holter recording.
AB - AIMS: Verification of the accuracy of onset, offset, and duration of automatic
mode switching (AMS) of pacemakers compared with onset and end of atrial
fibrillation (AF) or atrial tachycardia (AT). Correct pacemaker diagnosis of
atrial tachyarrhythmias (AA) is indispensable for reliable automatic prevention
and intervention algorithms of AA. METHODS AND RESULTS: Comparison was made of
the AMS registration of the pacemaker-stored electrograms (EGMs) and the number
and cumulative duration of these episodes with continuous 7-day Holter
monitoring. Atrial sensitivity was kept at 0.5 mV and far field R-wave
recognition in the atrial channel was excluded by blanking of this signal. Lead
types were confined to leads with short-ring tip spacing (10-13.8 mm). During
Holter monitoring, 18 of 57 included patients with standard reason for pacemaker
implantation showed episodes of AF or AT. Cumulative duration of AF and AT from
Holter was correctly interpreted by the pacemaker in 99.9% of the patients. All
episodes of AF, as seen on the Holter recording, were recognized by the pacemaker
(correlation 99.9%). During AF, multiple episodes of undersensing were detected.
The number of AMS episodes was influenced by undersensing during AF. The
influence of these short episodes of undersensing on the total duration of AF was
trivial (cumulative duration of AF was 99.9% correct). In patients with AT
without AF on Holter (n=7) and in contrast to the AF episodes, the cumulative AT
duration did not correlate well (63%) with the Holter recordings. The number of
AMS episodes in the setting of AT was influenced by the atrial tachycardia
detection rate setting and the duration of the post-ventricular atrial blanking
interval. CONCLUSION: The total duration of AF is correctly represented by the
total duration of AMS and can be considered a reliable measure of total AF
duration. AT duration was poorly correlated with AMS duration. The number of mode
switches does not reflect the number of episodes of AF/AT. Increased memory
capacity allowing the storing of all EGMs triggered by the initiation of AF/AT
would be the ideal setting with which to optimize the diagnostic performance of
pacemakers.
PMID- 17043070
TI - The effectiveness of a high output/short duration radiofrequency current
application technique in segmental pulmonary vein isolation for atrial
fibrillation.
AB - AIMS: Segmental pulmonary vein (PV) isolation by radiofrequency (RF) catheter
ablation has become a curative therapy for atrial fibrillation (AF). However, the
long procedure time limits the wide application of this procedure. The aim of the
current study was to compare a novel ablation technique with a high power output
and short application time vs. a conventional technique using a low power output
and long application time. METHODS AND RESULTS: The study included 90 consecutive
patients (age 53+/-10 years; 66 men). Segmental PV isolation was performed by
irrigated RF catheter ablation in both groups. In the conventional group (Group
1, 45 patients), the power output was limited to 30 W with a target temperature
of 50 degrees C and an RF preset duration of 120 s. In the novel group (Group 2,
45 patients), the maximum power output was preset to 45 W, with a target
temperature of 55 degrees C and duration of 20 s. In Group 2, a significant
reduction in the PV isolation time (127+/-57 vs. 94+/-33 min, P<0.02), mean
fluoroscopy time (73+/-23 vs. 55+/-16 min, P<0.001), and radiation dose was
observed. According to the application time and number, Group 2 showed a
reduction in RF application time, but a higher number of RF applications were
required for creation of complete PV isolation. During a mean follow-up of 15+/-7
months, a total of 74% of patients in Group 1 and 76% of patients in Group 2
demonstrated stable SR. CONCLUSION: Segmental PV isolation using a high power
output and short application time is safe and effective in PV isolation in
patients with AF. This technique can significantly reduce the procedure and
fluoroscopy time compared with a low-power output technique.
PMID- 17043071
TI - Substrate mapping vs. tachycardia mapping using CARTO in patients with coronary
artery disease and ventricular tachycardia: impact on outcome of catheter
ablation.
AB - AIMS: For ablation of ventricular tachycardia (VT) in patients after myocardial
infarction, a three-dimensional mapping system is often used. We report on our
overall success rate of VT ablation using CARTO in 47 patients, with a subgroup
analysis comparing VT mapping with the results of mapping that had to be
performed during sinus rhythm or pacing (substrate mapping). METHODS AND RESULTS:
A CARTO map was performed and VT ablation attempted using two strategies:
Patients in the VT-mapping group had incessant VT (four patients) or inducible
stable VT (18 patients) such that the circuit of the clinical VT could be
reconstructed using CARTO. During VT, the critical area of slow conduction was
identified using diastolic potentials and conventional concealed entrainment
pacing. In contrast, patients in the substrate-mapping group had initially
inducible VT. However, a complete VT map was not possible because of catheter
induced mechanical block (six patients) or because haemodynamics deteriorated
during the ongoing VT (19 patients). Therefore, pathological myocardium was
identified by fragmented, late- and/or low-amplitude (<1.5 mV) bipolar potentials
during sinus rhythm or pacing, and the ablation site was primarily determined by
pace mapping inside or at the border of this pathological myocardium. Acute
ablation success in all patients with regard to non-inducibility of the clinical
VT or any slower VT was 79% after a single ablation procedure, but increased to
95% after a mean of 1.2 ablation procedures. However, chronic success was 75%,
when it was defined as freedom from any ventricular tachyarrhythmia (VT or VF)
during a follow-up of 25+/-13 months. In the subgroup analysis, patients in the
VT-mapping group were not significantly different from patients in the substrate
mapping group with regard to age (65+/-7 vs. 65+/-9 years), ejection fraction
(30+/-7 vs. 30+/-8%), VT cycle length (448+/-81 vs. 429+/-82 ms), number of
radiofrequency applications (17+/-9 vs. 14+/-6 applications), use of an irrigated
tip catheter (23 vs. 32%), and ablation results. CONCLUSION: When using a CARTO
guided approach for VT ablation in patients with coronary artery disease, the
freedom from any ventricular arrhythmia is high (75%), but leaves the patient at
a 23% risk of developing fast VT/VF during follow-up. Mapping during sinus rhythm
or pacing is as successful as mapping during VT.
PMID- 17043072
TI - Cardiac pacing in sleep apnoea: diagnostic and therapeutic implications.
AB - The sleep apnoea syndrome is a particularly common health problem associated with
increased cardiovascular morbidity and mortality, as well as harmful
socioeconomical and familial complications. In this article, the diagnostic and
therapeutic role of cardiac pacing in this syndrome is discussed.
PMID- 17043073
TI - Impact of left ventricular epicardial and biventricular pacing on ventricular
repolarization in normal-heart individuals and patients with congestive heart
failure.
AB - AIMS: Malignant ventricular arrhythmias can arise in a subset of congestive heart
failure (CHF) patients after they undergo cardiac resynchronization therapy
(CRT), thus counteracting the haemodynamic benefits typically associated with
biventricular pacing. This study seeks to assess whether alteration of the
ventricular transmural repolarization and conduction due to reversal of the
depolarization sequence during epicardial or biventricular pacing facilitate the
development of ventricular arrhythmias. METHODS AND RESULTS: ECGs and monophasic
action potential (MAP) were recorded during programmed stimulation from right
ventricle (RV) endocardium (RV-Endo), left ventricle (LV) epicardium (LV-Epi), or
both (biventricular, Bi-V) in 15 individuals without structural heart diseases.
In patients with severe CHF and CRT (n=21), ECGs were collected during RV-Endo,
LV-Epi, and Bi-V pacing. MAP duration on intracardiac electrogram, the QT, JT,
and T(peak)-T(end) intervals on ECGs at different pacing sites were measured and
compared. In subjects with or without structural heart disease, compared with RV
Endo pacing, LV-Epi and Bi-V pacing resulted in a longer JT (341.78+/-61.97 ms
with LV-Epi, 325.86+/-59.69 ms with Bi-V vs. 286.14+/-38.68 ms with RV-Endo in
CHF individuals, P<0.0001) or T(peak)-T(end) interval (121.55+/-19.88 ms with LV
Epi, 117.71+/-42.63 ms with Bi-V vs. 102.28+/-12.62 ms with RV-Endo in normal
heart subjects, P<0.0001; 199.70+/-62.44 ms with LV-Epi, 184.89+/-74.08 ms with
Bi-V vs. 146.41+/-31.06 ms with RV-Endo in CHF patients, P<0.0001), in addition
to prolonged myocardial repolarization time and delayed endocardial activation.
During follow-up, sudden death and arrhythmia storm occurred in two CHF patients
after CRT. CONCLUSION: Epicardial and biventricular pacing prolong the time and
increase the dispersion of myocardial repolarization and delay the transmural
conduction. All of these should be considered as potential arrhythmogenic factors
in CHF patients who receive CRT.
PMID- 17043074
TI - Different working and living conditions and their associations with persistent
neck/shoulder and/or low back disorders.
AB - OBJECTIVES: To investigate whether different combinations of working and living
conditions are associated with the risk for persistent neck/shoulder and/or low
back disorders. The underlying purpose of this contextual approach was to
identify target groups for primary/secondary prevention. METHODS: In a baseline
study, 11 groups with different working and living conditions were identified by
cluster analysis. In this study, these 11 groups were followed up by a postal
questionnaire 5 years after baseline (response rate 82%, n = 1095). RESULTS: Five
of the groups--the onerous human services job, the free agent, the family burden,
the mentally stretched and the physically strained groups--had an increased risk
for persistent disorders (OR 2.38-2.70). Four of these groups had rather sex
specific working and living conditions. CONCLUSIONS: The results support the
hypothesis that different combinations of working and living conditions may
increase the risk for persistent neck/shoulder and/or low back disorders to
different degrees. Sex-specific working and living conditions increased the risk
for women as well as for men, irrespective of whether the conditions were
specific to women or men.
PMID- 17043075
TI - Exposure to carcinogens for defined job categories in Norway's offshore petroleum
industry, 1970 to 2005.
AB - OBJECTIVES: To identify and describe the exposure to selected known and suspected
carcinogenic agents, mixtures and exposure circumstances for defined job
categories in Norway's offshore petroleum industry from 1970 to 2005, in order to
provide exposure information for a planned cohort study on cancer. METHODS:
Background information on possible exposure was obtained through company visits,
including interviewing key personnel (n = 83) and collecting monitoring reports
(n = 118) and other relevant documents (n = 329). On the basis of a previous
questionnaire administered to present and former offshore employees in 1998, 27
job categories were defined. RESULTS: This study indicated possible exposure to
18 known and suspected carcinogenic agents, mixtures or exposure circumstances.
Monitoring reports were obtained on seven agents (benzene, mineral oil mist and
vapour, respirable and total dust, asbestos fibres, refractory ceramic fibres,
formaldehyde and tetrachloroethylene). The mean exposure level of 367 personal
samples of benzene was 0.037 ppm (range: less than the limit of detection to 2.6
ppm). Asbestos fibres were detected (0.03 fibres/cm3) when asbestos-containing
brake bands were used in drilling draw work in 1988. Personal samples of
formaldehyde in the process area ranged from 0.06 to 0.29 mg/m3. Descriptions of
products containing known and suspected carcinogens, exposure sources and
processes were extracted from the collected documentation and the interviews of
key personnel. CONCLUSIONS: This study described exposure to 18 known and
suspected carcinogenic agents, mixtures and exposure circumstances for 27 job
categories in Norway's offshore petroleum industry. For a planned cohort study on
cancer, quantitative estimates of exposure to benzene, and mineral oil mist and
vapour might be developed. For the other agents, information in the present study
can be used for further assessment of exposure, for instance, by expert
judgement. More systematic exposure surveillance is needed in this industry. For
future studies, new monitoring programmes need to be implemented.
PMID- 17043076
TI - Enhanced preventive programme at a beryllium oxide ceramics facility reduces
beryllium sensitisation among new workers.
AB - BACKGROUND: A 1998 survey at a beryllium oxide ceramics manufacturing facility
found that 10% of workers hired in the previous 6 years had beryllium
sensitisation as determined by the beryllium lymphocyte proliferation test
(BeLPT). In response, the facility implemented an enhanced preventive programme
to reduce sensitisation, including increased respiratory and dermal protection
and particle migration control. AIM: To assess the programme's effectiveness in
preventing sensitisation. METHODS: In 2000, the facility began testing newly
hired workers for beryllium sensitisation with the BeLPT at time of hire and
during employment. The sensitisation rate and prevalence for workers hired from
2000 to 2004 were compared with that for workers hired from 1993 to 1998, who
were tested in the 1998 survey. Facility environmental conditions for both time
periods were evaluated. RESULTS: Newly hired workers in both cohorts worked for a
mean of 16 months. Of the 97 workers hired from 2000 to 2004 with at least one
employment BeLPT result, four had abnormal results at time of hire and one became
sensitised during employment. Of the 69 workers hired from 1993 to 1998 and
tested in 1998, six were found to be sensitised. The sensitisation rate for the
2000-4 workers was 0.7-2.7/1000 person-months of employment, and that for the
1993-8 workers was 5.6/1000 person-months, at least 2.1 (95% confidence interval
(CI) 0.6 to 8.4) and up to 8.2 (95% CI 1.2 to 188.8) times higher than that for
the 2000-4 workers. The sensitisation prevalence for the 2000-4 workers was 1%
and that for the 1993-8 workers was 8.7%, 8.4 (95% CI 1.04 to 68.49) times higher
than that for the 2000-4 workers. Airborne beryllium levels for production
workers for the two time periods were similar. CONCLUSIONS: A comprehensive
preventive programme reduced beryllium sensitisation in new workers during the
first years of employment, despite airborne beryllium levels for production
workers that were similar to pre-programme levels.
PMID- 17043077
TI - Occupational exposure to low frequency magnetic fields and dementia: a case
control study.
AB - BACKGROUND: Several studies point to a potential aetiological relevance to
dementia of exposure to low-frequency magnetic fields, but the evidence is
inconclusive. OBJECTIVE: To further examine the relationship between low
frequency magnetic fields and dementia. METHODS: From 23 general practices, 195
patients with dementia were recruited. Of these, 108 had possible Alzheimer's
disease, 59 had possible vascular dementia and 28 had secondary or unclassified
dementia. A total of 229 controls were recruited: 122 population controls and 107
ambulatory patients free from dementia. Data were gathered in a structured
personal interview; in cases, the interview was administered to the next of kin.
Exposure to low-frequency electromagnetic fields was assessed by expert rating.
To identify occupations suspected to be associated with dementia, major
occupations were a priori formed. Odds ratios were calculated using logistic
regression, to control for age, region, sex, dementia in parents and smoking.
RESULTS: Exposure to magnetic fields was not significantly associated with
dementia; restriction of the analysis to cases with possible Alzheimer's disease
or possible vascular dementia did not lead to statistically significant results.
We found an increased risk of dementia in blue-collar occupations (electrical and
electronics workers, metal workers, construction workers, food and beverage
processors and labourers). CONCLUSIONS: Our study does not support a strong
association between occupational exposure to low-frequency magnetic fields and
dementia. Further studies should consider the relationship between blue-collar
work and the late development of dementia.
PMID- 17043078
TI - Multidisciplinary consensus on the terminology and classification of complaints
of the arm, neck and/or shoulder.
AB - BACKGROUND: There is no universally accepted way of labelling or defining upper
extremity musculoskeletal disorders. A variety of names are used and many
different classification systems have been introduced. OBJECTIVE: To agree on an
"unambiguous language" concerning the terminology and classification that can be
used by all relevant medical and paramedical disciplines in the Netherlands.
METHODS: A Delphi consensus strategy was initiated. The outcomes of a
multidisciplinary conference were used as a starting point. In total, 47 experts
in the field of upper-extremity musculoskeletal disorders were delegated by 11
medical and paramedical professional associations to form the expert panel for
the Delphi consensus strategy. Each Delphi round consisted of a questionnaire, an
analysis and a feedback report. RESULTS: After three Delphi rounds, consensus was
achieved. The experts reported the consensus in a model. This so-called CANS
model describes the term, definition and classification of complaints of arm,
neck and/or shoulder (CANS) and helps professionals to classify patients
unambiguously. CANS is defined as "musculoskeletal complaints of arm, neck and/or
shoulder not caused by acute trauma or by any systemic disease". The experts
classified 23 disorders as specific CANS, because they were judged as diagnosable
disorders. All other complaints were called non-specific CANS. In addition, the
experts defined "alert symptoms" on the top of the model. CONCLUSIONS: The use of
the CANS model can increase accurate and meaningful communication among
healthcare workers, and may also have a positive influence on the quality of
scientific research, by enabling comparison of data of different studies.
PMID- 17043079
TI - Leukocyte telomere length and cardiovascular disease in the cardiovascular health
study.
AB - The telomere length of replicating somatic cells is inversely correlated with age
and has been reported to be associated cross-sectionally with cardiovascular
disease (CVD). Leukocyte telomere length, as expressed by mean terminal
restriction fragment (TRF) length, was measured in 419 randomly selected
participants from the Cardiovascular Health Study, comprising a community
dwelling cohort recruited in four US communities. The authors investigated
associations between TRF length and selected measures of subclinical CVD/risk
factors for CVD (data were collected at the 1992/1993 clinic visit) and incident
CVD (ascertained through June 2002). In these participants (average age = 74.2
years (standard deviation, 5.2)), mean TRF length was 6.3 kilobase pairs
(standard deviation, 0.62). Significant or borderline inverse associations were
found between TRF length and diabetes, glucose, insulin, diastolic blood
pressure, carotid intima-media thickness, and interleukin-6. Associations with
body size and C-reactive protein were modified by gender and age, occurring only
in men and in participants aged 73 years or younger. In younger (but not older)
participants, each shortened kilobase pair of TRF corresponded with a threefold
increased risk of myocardial infarction (hazard ratio = 3.08, 95% confidence
interval: 1.22, 7.73) and stroke (hazard ratio = 3.22, 95% confidence interval:
1.29, 8.02). These results support the hypotheses that telomere attrition may be
related to diseases of aging through mechanisms involving oxidative stress,
inflammation, and progression to CVD.
PMID- 17043080
TI - Re: "when is baseline adjustment useful in analyses of change? An example with
education and cognitive change".
PMID- 17043081
TI - Tissue growth in a rotating bioreactor. Part II: fluid flow and nutrient
transport problems.
AB - Fluid flow and nutrient transport around a growing tissue construct within a
cylindrical bioreactor of circular cross-section are considered. The bioreactor
is filled with nutrient-rich culture medium, and the growing tissue construct is
modelled as a cylindrical obstacle, also of circular cross-section, at a given
(moving) position within the nutrient solution. The bioreactor rotates about its
cylindrical axis, and its axial length is small relative to its radius (the high
aspect ratio vessel bioreactor). This small-aspect ratio means that a simple
idealized model may be considered, in which (leading order) quantities are
averaged across the axial direction. The leading-order fluid flow is then of Hele
Shaw type, and may be solved for explicitly. The trajectory of the tissue
construct within the rotating bioreactor is determined by analysis of the various
forces acting on it. Several different modes of motion are found to be possible,
depending on the experimental conditions, and examples of each type of motion are
presented. Additionally, we solve the problem for the nutrient transport around
the tissue construct in the special case in which the construct remains fixed in
the laboratory frame, and (as the cells proliferate in response to the nutrient
available locally) deduce growth rates for the construct. Finally, we discuss our
results in the light of possible experimental bioreactor set-ups. We note the
present model's limitations, and consider how our work could be extended and
improved to inform experimental protocols in future.
PMID- 17043082
TI - Neural populations can induce reliable postsynaptic currents without observable
spike rate changes or precise spike timing.
AB - Fine temporal patterns of firing in much of the brain are highly irregular. In
some circuits, the precise pattern of irregularity contains information beyond
that contained in mean firing rates. However, the capacity of neural circuits to
use this additional information for computational purposes is not well
understood. Here we employ computational methods to show that an ensemble of
neurons firing at a constant mean rate can induce arbitrarily chosen temporal
current patterns in postsynaptic cells. If the presynaptic neurons fire with
nearly uniform interspike intervals, then current patterns are sensitive to
variations in spike timing. But irregular, Poisson-like firing can drive current
patterns robustly, even if spike timing varies by tens of milliseconds from trial
to trial. Notably, irregular firing patterns can drive useful patterns of current
even if they are so variable that several hundred repeated experimental trials
would be needed to distinguish them from random firing. Together, these results
describe an unrestrictive set of conditions in which postsynaptic cells might
exploit virtually any information contained in spike timing. We speculate as to
how this capability may underlie an extension of population coding to the
temporal domain.
PMID- 17043084
TI - Molecular interaction between Methylobacterium extorquens and seedlings: growth
promotion, methanol consumption, and localization of the methanol emission site.
AB - Four Methylobacterium extorquens strains were isolated from strawberry (Fragaria
x ananassa cv. Elsanta) leaves, and one strain, called ME4, was tested for its
ability to promote the growth of various plant seedlings. Seedling weight and
shoot length of Nicotiana tabacum, Lycopersicon esculentum, Sinapis alba, and
Fragaria vesca increased significantly in the presence of the pink-pigmented
facultative methylotroph (PPFM), but the germination behaviour of seeds from six
other plants was not affected. The cell-free supernatant of the bacterial culture
stimulated germination, suggesting the production of a growth-promoting agent by
the methylotroph. Methanol emitted from N. tabacum seedlings, as determined by
proton-transfer-reaction mass spectrometry (PTR-MS), ranged from 0.4 to 0.7 ppbv
(parts per billion by volume), while significantly lower levels (0.005 to 0.01
ppbv) of the volatile alcohol were measured when the seedlings were co-cultivated
with M. extorquens ME4, demonstrating the consumption of the gaseous methanol by
the bacteria. Additionally, by using cells of the methylotrophic yeast Pichia
pastoris transformed with the pPICHS/GFP vector harbouring a methanol-sensitive
promoter in combination with the green fluorescence protein (GFP) reporter gene,
stomata were identified as the main source of the methanol emission on tobacco
cotyledons. Methylobacterium extorquens strains can nourish themselves using the
methanol released by the stomata and release an agent promoting the growth of the
seedlings of some crop plants.
PMID- 17043083
TI - The apoplastic antioxidant system in Prunus: response to long-term plum pox virus
infection.
AB - This work describes, for the first time, the changes taking place in the
antioxidative system of the leaf apoplast in response to plum pox virus (PPV) in
different Prunus species showing different susceptibilities to PPV. The presence
of p-hydroxymercuribenzoic acid (pHMB)-sensitive ascorbate peroxidase (APX)
(class I APX) and pHMB-insensitive APX (class III APX), superoxide dismutase
(SOD), peroxidase (POX), NADH-POX, and polyphenoloxidase (PPO) was described in
the apoplast from both peach and apricot leaves. PPV infection produced different
changes in the antioxidant system of the leaf apoplast from the Prunus species,
depending on their susceptibility to the virus. In leaves of the very susceptible
peach cultivar GF305, PPV brought about an increase in class I APX, POX, NADH
POX, and PPO activities. In the susceptible apricot cultivar Real Fino, PPV
infection produced a decrease in apoplastic POX and SOD activities, whereas a
strong increase in PPO was observed. However, in the resistant apricot cultivar
Stark Early Orange, a rise in class I APX as well as a strong increase in POX and
SOD activities was noticed in the apoplastic compartment. Long-term PPV infection
produced an oxidative stress in the apoplastic space from apricot and peach
plants, as observed by the increase in H2O2 contents in this compartment.
However, this increase was much higher in the PPV-susceptible plants than in the
resistant apricot cultivar. Only in the PPV-susceptible apricot and peach plants
was the increase in apoplastic H2O2 levels accompanied by an increase in
electrolyte leakage. No changes in the electrolyte leakage were observed in the
PPV-inoculated resistant apricot leaves, although a 42% increase in the
apoplastic H2O2 levels was produced. Two-dimensional electrophoresis analyses
revealed that the majority of the polypeptides in the apoplastic fluid had
isoelectric points in the range of pI 4-6. The identification of proteins using
MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) and
peptide mass fingerprinting analyses showed the induction of a thaumatin-like
protein as well as the decrease of mandelonitrile lyase in peach apoplast due to
PPV infection. However, most of the selected polypeptides showed no homology with
known proteins. This fact emphasizes that, at least in Prunus, most of the
functions of the apoplastic space remain unknown. It is concluded that long-term
PPV infection produced an oxidative stress in the leaf apoplast, contributing to
the deleterious effects produced by PPV infection in leaves of inoculated,
susceptible Prunus plants.
PMID- 17043085
TI - Leaf hairs influence phytopathogenic fungus infection and confer an increased
resistance when expressing a Trichoderma alpha-1,3-glucanase.
AB - The leaf surface of a very large number of plant species are covered by
trichomes. Non-glandular trichomes are specialized unicellular or multicellular
structures that occur in many different plant species and function in xenobiotic
detoxification and protecting the plant against pest attack. By analysing the
susceptibility of trichome mutants, evidence is provided that indicates the
influence of leaf trichomes on foliar fungal infections in Arabidopsis thaliana,
probably by facilitating the adhesion of the fungal spores/hyphae to the leaf
surface. A decreased trichome number in the hairless Arabidopsis mutant gl1
enhances tolerance against the necrotrophic fungus Botrytis cinerea. By contrast,
the try mutant shows an increased susceptibility to both fungal infection and
accumulation. Trichome density does not influence infection by the soil-borne
pathogen Rhizoctonia solani. In addition, the influence of trichomes on foliar
infection is supported by targeting the high-level expression of the Trichoderma
harzianum alpha-1,3-glucanase protein to the specialized cell structures.
Trichome expression of this anti-fungal hydrolase shows a significant resistance
to infection by the foliar pathogen Botrytis cinerea. Resistance to this fungus
is not dependent on the constitutive induction of the salicylic or jasmonic
defence signalling pathways, but the presence of the alpha-1,3-glucanase protein
in trichomes.
PMID- 17043086
TI - Expression profiling of Chondrus crispus (Rhodophyta) after exposure to methyl
jasmonate.
AB - Methyl jasmonate (MeJA) is a plant hormone important for the mediation of signals
for developmental processes and defence reactions in higher plants. The effects
of MeJA and the signalling pathways on other photosynthetic organism groups are
largely unknown, even though MeJA may have very important roles. Therefore the
effects of MeJA in a red alga were studied. A medium-scale expression profiling
approach to identify genes regulated by MeJA in the red seaweed Chondrus crispus
is described here. The expression profiles were studied 0, 2, 4, 6, 12, and 24 h
after the addition of MeJA to the seawater surrounding the algae. The changes in
the transcriptome were monitored using cDNA microarrays with 1920 different cDNA
representing 1295 unique genes. The responses of selected genes were verified
with real-time PCR and the correlation between the two methods was generally
satisfying. The study showed that 6% of genes studied showed a response to the
addition of MeJA and the most dynamic response was seen after 6 h. Genes that
showed up-regulation included several glutathione S-transferases, heat shock
protein 20, a xenobiotic reductase, and phycocyanin lyase. Down-regulated
transcripts included glucose kinase, phosphoglucose isomerase, and a ribosomal
protein. A comparison between different functional groups showed an up-regulation
of stress-related genes and a down-regulation of genes involved in energy
conversion and general metabolism. It is concluded that MeJA, or a related
compound, has a physiological role as a stress hormone in red algae. This study
represents to our knowledge the first analysis of gene expression using cDNA
microarrays in a red macroalga.
PMID- 17043087
TI - MtArt: a new model of amino acid replacement for Arthropoda.
AB - A statistical approach was applied to select those models that best fit each
individual mitochondrial (mt) protein at different taxonomic levels of metazoans.
The existing mitochondrial replacement matrices, MtREV and MtMam, were found to
be the best-fit models for the mt-proteins of vertebrates, with the exception of
Nd6, at different taxonomic levels. Remarkably, existing mitochondrial matrices
generally failed to best-fit invertebrate mt-proteins. In an attempt to better
model the evolution of invertebrate mt-proteins, a new replacement matrix, named
MtArt, was constructed based on arthropod mt-proteomes. The new model was found
to best fit almost all analyzed invertebrate mt-protein data sets. The observed
pattern of model fit across the different data sets indicates that no single
replacement matrix is able to describe the general evolutionary properties of mt
proteins but rather that taxonomical biases and/or the existence of different mt
genetic codes have great influence on which model is selected.
PMID- 17043088
TI - Protein-energy supplements to preserve nutritional status of sugar cane cutters.
AB - BACKGROUND: Sugar cane cutters in south-eastern Brazil are temporarily hired for
the harvest period of 8 months. They often have minimal benefits and may not
receive adequate nutrition. AIMS: To evaluate alterations in weight and body
composition of sugar cane cutters during harvest with the use of protein-energy
and electrolyte supplements. METHODS: Three products were used daily: a milk
drink, a seasoned manioc meal mixture and an electrolyte replacement fluid,
adding approximately 398 kcal and 28.5 g of protein/day. RESULTS: There were
small, but significant, reductions in body mass index and percentage body fat
with maintenance of lean mass. There was a significant improvement in hydration
status, serum albumin and cholesterol. There were no medical absences related to
dehydration. CONCLUSIONS: Even though alterations in body mass and biochemistry
were small, the significance of the findings suggests these supplements may have
a useful role to play in reducing lean mass losses and maintaining nutritional
and hydration status of these workers.
PMID- 17043089
TI - Activity, functional capacity and well-being in ageing Finnish workers.
AB - BACKGROUND: The ageing of the labour force and falling employment rates have
forced policy makers in industrialized countries to find means of increasing the
well-being of older workers and of lengthening their work careers. AIMS: To
longitudinally study the relationship between activity and functional capacity
and the well-being of ageing workers. METHODS: Follow-up study to that carried
out by the Finnish Institute of Occupational Health in 1981-97 (n = 3817).
Activity level was measured using various free-time activities, and functional
capacity was measured through daily-life activities. The measure of well-being
included items with both positive and negative affects. The associations between
activity, functional capacity and well-being were analysed by general linear
models with repeated measures. RESULTS: Activity level and functional capacity
had a strong positive effect (the effects of one unit increase were 0.32 and
0.30, respectively) on well-being. They were also interdependent. The impact of
activity level in maintaining well-being became 31% greater during the follow-up,
whereas the effect of functional capacity diminished by 17%. CONCLUSION: The
results of the study indicate that both involvement in activities and functional
capacity have an important, partly compensatory role in maintaining the well
being of ageing workers.
PMID- 17043090
TI - Effects of overtime work on blood pressure and body mass index in Japanese male
workers.
AB - BACKGROUND: Effects of overtime work on health is a controversial issue. AIMS: To
determine the effects of overtime work on blood pressure and body mass index
(BMI) for male workers in Japan. METHODS: Participants were 323 male participants
of three companies. Data were collected by occupational physicians at periodic
physical examinations and additional examinations. The time courses for the
development of definite hypertension and an increase in BMI were recorded. The
Kaplan-Meier method was used to estimate the cumulative incidence rates of
developing definite hypertension and increasing BMI, and the Cox proportional
hazard model was used to determine the adjusted relative hazard of overtime work.
RESULTS: The age-adjusted incidence rates of developing definite hypertension and
increasing BMI were significantly lower among the participants whose mean
overtime was > or =50 h than among those whose mean overtime was <50 h/month (log
rank P < 0.05). The Cox proportional hazard model indicated that those who worked
a mean overtime of > or =50 h/month had lower risks of developing definite
hypertension (hazard ratio, 0.36; 95% CI, 0.15-0.88; P < 0.05) and increasing
their BMI (hazard ratio, 0.44; 95% CI, 0.31-0.63; P < 0.01) after adjusting for
age. CONCLUSIONS: The results of this study indicate that workers whose mean
overtime was > or =50 h have lower risks of developing definite hypertension and
increasing their BMI.
PMID- 17043091
TI - Clinicopathological features of pyothorax-associated lymphoma; a retrospective
survey involving 98 patients.
AB - To investigate clinicopathological features of pyothorax-associated lymphoma
(PAL), we examined medical records of 98 patients (88 males and 10 females) with
PAL at a median age of 70 years (range 51-86). Seventy-nine patients had a
history of artificial pneumothorax. Median interval between diagnosis and
artificial pneumothorax was 43 years (range 19-64). At diagnosis, performance
status (PS) was 0-1 (n=56) and 2-4 (n=42). Clinical stages were I (n=42), II
(n=26), III (n=8) and IV (n=22). Pathological diagnosis comprised diffuse large-B
cell (n=78) and peripheral T-cell lymphoma (n=1). Seventeen were treated
supportively. The other 81 received aggressive treatments; chemotherapy (n=52),
radiotherapy (n=7), surgery (n=4) and combination (n=18). Five-year overall
survival (OS) was 0.35 (95% confidence interval, 24% to 45%). Causes of deaths
were PAL (n=39), respiratory failure (n=13) and others (n=12). Multivariate
analysis identified prognostic factors for OS; lactate dehydrogenase levels
[hazard ratio (HR)=2.36; P=0.013], sex (female versus male) (HR=0.15; P=0.01), PS
(2-4 versus 0-1) (HR=2.20; P=0.02), clinical stages (III/IV versus I/II)
(HR=1.95; P=0.037) and chemotherapy (HR=0.31; P=0.01). Most patients with PAL are
elderly and have comorbidities, while some of them achieve durable remission with
appropriate treatments. These findings prompt us to establish an optimal
treatment strategy on the basis of risk stratification of individual patients.
PMID- 17043092
TI - Predicting prognosis in patients with advanced cancer.
AB - BACKGROUND: Patients with advanced cancer and their carers frequently wish to
know how long they can expect to live. Improved prognostication would enable
patients and their carers to be better prepared for their impending death, and
would allow clinicians to make better informed decisions about place of care.
However, clinician estimates of survival are inaccurate and systematically
overoptimistic. Recently, attempts have been made to improve upon clinician
estimates of survival by devising prognostic scales incorporating clinical
information with biochemical and haematological results. DESIGN: A descriptive
and critical review of palliative prognostic scales, on the basis of the
recommendations of the European Association of Palliative Care prognosis working
group (2005) supplemented by an Ovid Medline search 1966-March 2006 using the key
words 'prognosis', 'neoplasms', 'palliative care' and 'terminal care'. RESULTS:
This paper reviews the advantages and limitations of the palliative prognostic
score, the palliative prognostic index, the Chuang prognostic scale, the terminal
cancer prognostic score and the poor prognostic indicator. CONCLUSIONS: All the
currently available prognostic scales have limitations, but nonetheless offer an
improvement on unadjusted clinician estimates of survival. Further research is
required to systematically develop a prognostic scale on the basis of all the
known prognostic variables in patients with advanced cancer.
PMID- 17043093
TI - The cost-effectiveness of bisphosphonates in metastatic breast cancer: letter to
the editor in response to Botteman et al. 2006.
PMID- 17043094
TI - Randomized phase II trial of gemcitabine plus weekly versus three-weekly
paclitaxel in previously untreated advanced non-small-cell lung cancer.
AB - INTRODUCTION: Gemcitabine and paclitaxel (Taxol) each provides an efficacious non
platinum option for the treatment of advanced non-small-cell lung cancer (NSCLC),
but the optimal dosage and schedule of the two agents used in combination are not
well defined. METHODS: Previously untreated patients with advanced NSCLC were
randomized to receive gemcitabine-paclitaxel on a traditional three-weekly
schedule (Arm A) or a novel weekly schedule (Arm B) as follows-Arm A (three
weekly): gemcitabine 1000 mg/m2 infused>30 min on days 1 and 8 and paclitaxel 200
mg/m2 infused>3 h on day 1 of a 21-day cycle or Arm B (weekly): gemcitabine 1000
mg/m2 infused>30 min and paclitaxel 100 mg/m2 infused>1 h, both administered on
days 1 and 8 of a 21-day cycle. RESULTS: One hundred patients received at least
one dose of treatment. The weekly schedule, Arm B, was more efficacious and less
hematologically toxic than Arm A. Confirmed complete and partial response rates
were 28.2% and 26.8%, respectively. Median survival was 10.3 months on Arm B and
7.9 months on Arm A (log-rank P=0.10); 1- and 2-year survival rates also favor
Arm B: 42.0% versus 34.0% and 18.0% versus 6.0%. Progression-free survival was
5.8 versus 4.8 months, again favoring Arm B (log-rank P=0.06). There was a two
fold lower frequency of grade 3/4 hematologic events with Arm B as follows:
neutropenia (16% versus 30%), thrombocytopenia (4% versus 8%), and anemia (2%
versus 6%). One patient (2%) in each treatment group developed febrile
neutropenia. CONCLUSION: In this trial, both schedules were efficacious and
tolerable, although the weekly schedule resulted in improved survival and lower
hematologic toxicity compared with a three-weekly schedule. The weekly schedule
of gemcitabine-paclitaxel indicates an improved therapeutic index.
PMID- 17043095
TI - Henoch-Schonlein purpura (HSP) during treatment with anastrozole.
PMID- 17043096
TI - Artificial sweeteners and cancer risk in a network of case-control studies.
AB - BACKGROUND: The role of sweeteners on cancer risk has been widely debated over
the last few decades. To provide additional information on saccharin and other
sweeteners (mainly aspartame), we considered data from a large network of case
control studies. METHODS: An integrated network of case-control studies has been
conducted between 1991 and 2004 in Italy. Cases were 598 patients with incident,
histologically confirmed cancers of the oral cavity and pharynx, 304 of the
oesophagus, 1225 of the colon, 728 of the rectum, 460 of the larynx, 2569 of the
breast, 1031 of the ovary, 1294 of the prostate and 767 of the kidney (renal cell
carcinoma). Controls were 7028 patients (3301 men and 3727 women) admitted to the
same hospitals as cases for acute, non-neoplastic disorders. Odds ratios (ORs),
and the corresponding 95% confidence intervals (CIs), were derived by
unconditional logistic regression models. RESULTS: The ORs for consumption of
saccharin were 0.83 (95% CI 0.30-2.29) for cancers of the oral cavity and
pharynx, 1.58 (95% CI 0.59-4.25) for oesophageal, 0.95 (95% CI 0.67-1.35) for
colon, 0.93 (95% CI 0.60-1.45) for rectal, 1.55 (95% CI 0.76-3.16) for laryngeal,
1.01 (95% CI 0.77-1.33) for breast, 0.46 (95% CI 0.29-0.74) for ovarian, 0.91
(95% CI 0.59-1.40) for prostate and 0.79 (95% CI 0.49-1.28) for kidney cancer.
The ORs for consumption of other sweeteners, mainly aspartame, were 0.77 (95% CI
0.39-1.53) for cancers of the oral cavity and pharynx, 0.77 (95% CI 0.34-1.75)
for oesophageal, 0.90 (95% CI 0.70-1.16) for colon, 0.71 (95% CI 0.50-1.02) for
rectal, 1.62 (95% CI 0.84-3.14) for laryngeal, 0.80 (95% CI 0.65-0.97) for
breast, 0.75 (95% CI 0.56-1.00) for ovarian, 1.23 (95% CI 0.86-1.76) for prostate
and 1.03 (95% CI 0.73-1.46) for kidney cancer. A significant inverse trend in
risk for increasing categories of total sweeteners was found for breast and
ovarian cancer, and a direct one for laryngeal cancer. CONCLUSION: The present
work indicates a lack of association between saccharin, aspartame and other
sweeteners and the risk of several common neoplasms.
PMID- 17043097
TI - Role of fluorodeoxyglucose positron emission tomography in the staging of
patients with breast cancer candidated to surgery.
PMID- 17043098
TI - Chemical genomic profiling for identifying intracellular targets of toxicants
producing Parkinson's disease.
AB - The yeast deletion collection includes approximately 4700 strains deleted for
both copies of every nonessential gene. This collection is a powerful resource
for identifying the cellular pathways that functionally interact with drugs. In
the present study, the complete pool of approximately 4700 barcoded homozygous
deletion strains of Saccharomyces cerevisiae were surveyed to identify
genes/pathways interacting with 1-methyl-4-phenylpyridinium (MPP(+)) and N,N
dimethyl-4-4-bipiridinium (paraquat), neurotoxicants that can produce Parkinson's
disease. Each yeast mutant is molecularly "barcoded" the collections can be grown
competitively and ranked for sensitivity by microarray hybridization. Analysis
data from these screens allowed us to determine that the multivesicular body
pathway is an important element of toxicity induced by both MPP(+) and paraquat.
When yeast genes that when deleted showed sensitivity to MPP(+) and paraquat
toxicity were analyzed for their homology to human genes, 80% were found to have
highly conserved human homologs (with e < 10(-8)). Future work will address if
these human genes may also functionally interact with MPP(+) and paraquat
toxicity.
PMID- 17043099
TI - Human oviductal epithelial cells express Toll-like receptor 3 and respond to
double-stranded RNA: Fallopian tube-specific mucosal immunity against viral
infection.
AB - BACKGROUND: The aim of this study was to evaluate the site-specific
immunoregulatory mechanisms against viral infection in human Fallopian tubes.
METHODS: We therefore investigated the effects of double-stranded RNA (dsRNA) on
the production of interleukin (IL)-6, IL-8 and granulocyte chemotactic protein-2
(GCP-2) by cultured oviductal epithelial cells (OECs) using enzyme-linked
immunosorbent assays. Phosphorylation of inhibitor kappaB-alpha (IkappaB-alpha)
protein after dsRNA stimulation and the expression of Toll-like receptor (TLR) 3
in these cells were also evaluated by western blot analysis. RESULTS:
Polyriboinosinic:polyribocytidylic acid (poly I:C), a synthetic dsRNA that
antagonizes TLR3, stimulated the secretion of IL-6, IL-8 and GCP-2 by OECs. Poly
I:C-induced production of these cytokines by OECs was inhibited by the
pretreatment of these cells with anti-TLR3 antibody. The phosphorylation of
IkappaB-alpha protein was detected in OECs after stimulation by poly I:C. The
expression of TLR3 was also detected in OECs. CONCLUSION: These results suggest
that the epithelial cells of the human Fallopian tube have evolved a unique, site
specific mechanism for recognizing viral infection. TLR3-mediated production of
proinflammatory cytokines and chemokines in OECs in response to viral dsRNA may
be important for antiviral immunity in the human female reproductive tract.
PMID- 17043100
TI - Menstrual cycle-dependent changes of Toll-like receptors in endometrium.
AB - BACKGROUND: Rapid innate immune defences against infection usually involve the
recognition of invading pathogens by specific pattern recognition receptors
recently attributed to the family of Toll-like receptors (TLRs). Reports from our
laboratory and others have demonstrated the existence of TLRs 1-6 in the female
reproductive tract. However, little has been done to identify TLRs 7-10 in the
female reproductive tract, particularly in the uterus. Also little information
exists regarding variation in TLRs in the female reproductive tract during the
menstrual cycle. METHOD: The distribution of TLR7-10 protein was detected by
immunostaining in timed endometrial biopsies from normal women. RT-PCR was used
to show the existence of TLR1-10 genes in endometrial tissue and real-time PCR
analysis to investigate the relative expression of these genes during the
menstrual cycle in normal human endometrium. RESULTS: TLR7-10 proteins were
detected in endometrial epithelium and stroma. TLR1-10 genes were expressed in
human endometrial tissue, and the mean relative expression of TLR2-6, 9 and 10
genes was significantly higher during the secretory phase compared with other
phases of the menstrual cycle. CONCLUSIONS: TLR7-10 localization is not limited
to endometrial epithelium but is also present in the stroma of the endometrial
tissue. Endometrial TLR2-6, 9 and 10 genes are cyclically expressed during the
menstrual cycle.
PMID- 17043101
TI - Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection.
AB - Gastrointestinal nematode infections are prevalent worldwide and are potent
inducers of T helper 2 responses with the capacity to modulate the immune
response to heterologous antigens. Parasitic helminth infection has even been
shown to modulate the immune response associated with autoimmune diseases.
Nonobese diabetic (NOD) mice provide a model for studying human autoimmune
diabetes; as in humans, the development of diabetes in NOD mice has been linked
to the loss of self-tolerance to beta cell autoantigens. Previous studies with
the NOD mouse have shown that helminth and bacterial infection appears to inhibit
type 1 diabetes by disrupting the pathways leading to the Th1-mediated
destruction of insulin-producing beta cells. The aim of our study was to examine
whether infection with the gastrointestinal helminths Trichinella spiralis or
Heligmosomoides polygyrus could inhibit the development of autoimmune diabetes in
NOD mice and to analyze the mechanisms involved in protection and the role of Th2
responses. Protection from diabetes was afforded by helminth infection, appeared
to inhibit autoimmune diabetes by disrupting pathways leading to the destruction
of beta cells, and was mediated by seemingly independent mechanisms depending on
the parasite but which may be to be related to the capacity of the host to mount
a Th2 response.
PMID- 17043102
TI - Proteolytic processing of the Cryptosporidium glycoprotein gp40/15 by human furin
and by a parasite-derived furin-like protease activity.
AB - The apicomplexan parasite Cryptosporidium causes diarrheal disease worldwide.
Proteolytic processing of proteins plays a significant role in host cell invasion
by apicomplexan parasites. In previous studies, we described gp40/15, a
Cryptosporidium sp. glycoprotein that is proteolytically cleaved to yield two
surface glycopeptides (gp40 and gp15), which are implicated in mediating
infection of host cells. In the present study, we showed that biosynthetically
labeled gp40/15 is processed in Cryptosporidium parvum-infected HCT-8 cells. We
identified a putative furin cleavage site RSRR downward arrow in the deduced
amino acid sequence of gp40/15 from C. parvum and from all Cryptosporidium
hominis subtypes except subtype 1e. Both human furin and a protease activity
present in a C. parvum lysate cleaved recombinant C. parvum gp40/15 protein into
2 peptides, identified as gp40 and gp15 by size and by immunoreactivity with
specific antibodies. C. hominis gp40/15 subtype 1e, in which the RSRR sequence is
replaced by ISKR, has an alternative furin cleavage site (KSISKR downward arrow)
and was also cleaved by both furin and the C. parvum lysate. Site-directed
mutagenesis of the C. parvum RSRR sequence to ASRR resulted in inhibition of
cleavage by furin and the C. parvum lysate. Cleavage of recombinant gp40/15 and a
synthetic furin substrate by the C. parvum lysate was inhibited by serine
protease inhibitors, by the specific furin inhibitor decanoyl-Arg-Val-Lys-Arg
chloromethylketone (Dec-RVKR-cmk), and by calcium chelators, suggesting that the
parasite expresses a Ca2+ dependent, furin-like protease activity. The furin
inhibitor Dec-RVKR-cmk decreased C. parvum infection of HCT-8 cells, suggesting
that a furin-like protease activity may be involved in mediating host-parasite
interactions.
PMID- 17043103
TI - Protein P200 is dispensable for Mycoplasma pneumoniae hemadsorption but not
gliding motility or colonization of differentiated bronchial epithelium.
AB - Mycoplasma pneumoniae protein P200 was localized to the terminal organelle, which
functions in cytadherence and gliding motility. The loss of P200 had no impact on
binding to erythrocytes and A549 cells but resulted in impaired gliding motility
and colonization of differentiated bronchial epithelium. Thus, gliding may be
necessary to overcome mucociliary clearance.
PMID- 17043104
TI - Dendritic cell-derived exosomes express a Streptococcus pneumoniae capsular
polysaccharide type 14 cross-reactive antigen that induces protective
immunoglobulin responses against pneumococcal infection in mice.
AB - Exosomes activate T cells in vivo, but whether exosomes are able to induce
humoral immune responses is still unknown. We found that dendritic cells, but not
other immune cells, constitutively release an exosome-associated glycoconjugate
that is cross-reactive with the capsular polysaccharide of Streptococcus
pneumoniae type 14 (Cps14-CRA). Cps14-CRA was localized to the cholesterol
enriched microdomains or rafts of the exosomes and was mapped to the beta1-->6
branched N-acetyl-lactosamine derivatives of the Cps14-CRA. Injection of CFA
primed naive mice with purified dendritic cell exosomes induced immunoglobulin
(Ig) anti-Cps14 responses composed predominantly of IgM, IgG3, and IgG1. These
responses were associated with protection against a lethal challenge with live S.
pneumoniae type 14, but not with type 3 bacteria, and was correlated with the
titer of elicited IgM and IgG3 anti-Cps14. These data show, for the first time,
that exosomes can induce a humoral immune response to an associated unprocessed,
autologous antigen. Although anti-Cps14 Ig responses are specifically
demonstrated, these could reflect a broader mechanism that modulates both natural
immunity and autoimmunity to other glycotopes.
PMID- 17043105
TI - Limited role for CD4+ T-cell help in the initial priming of Trypanosoma cruzi
specific CD8+ T cells.
AB - Immune control of the protozoan parasite Trypanosoma cruzi requires the
activation of both CD4+ and CD8+ T cells. We recently identified two T. cruzi
trans-sialidase peptides that are targets of approximately 30% of all CD8+ T
cells during acute T. cruzi infection in mice. To determine whether CD4+ T cells
are required for generation of these dominant CD8+ T-cell responses, major
histocompatibility complex class II (MHC II)-deficient mice were infected with
the Brazil strain of T. cruzi and examined for the generation of antigen-specific
CD8+ T cells. Strong trans-sialidase TSKB18- and TSKB20-specific CD8+ T-cell
responses were generated in both the presence and the absence of CD4+ help.
However, the magnitudes of the immunodominant TSKB20-specific CD8+ T-cell
responses detectable using class I MHC-peptide tetramers were consistently lower
in the blood and spleens of MHC II-deficient mice. Spleen cells from infected MHC
II-deficient mice produced gamma interferon after in vitro stimulation with T.
cruzi peptides at levels similar to those in wild-type mice, and MHC II-deficient
mice displayed strong T. cruzi peptide-specific cytotoxic T-lymphocyte activity
in vivo. Thus, primary CD8+ T-cell responses in experimental T. cruzi infection
are generated in the absence of CD4+ T cells, providing further evidence that T.
cruzi directly activates and licenses antigen-presenting cells. Nevertheless,
unhelped CD8+ T cells in T. cruzi-infected mice fail to reach the frequencies
achieved in the presence of CD4 T-cell help and are unable to prevent acute-phase
death of these mice.
PMID- 17043106
TI - Serratia marcescens serralysin induces inflammatory responses through protease
activated receptor 2.
AB - The Serratia marcescens-derived protease serralysin is considered to play an
important role in the pathogenesis of infection. Protease-activated receptor 2
(PAR-2) is activated by trypsin and also several other trypsin-like serine
proteases, leading to the modulation of inflammatory and immune responses.
However, little is known about the activation of PAR-2 by bacterial proteases and
its roles in bacterial infection. In this study, we investigated whether S.
marcescens serralysin activates host inflammatory responses through PAR-2. Our
results demonstrated that serralysin induces interleukin-6 (IL-6) and IL-8 mRNA
expression in a human lung squamous cell carcinoma, EBC-l cells. In addition,
serralysin activated activator protein 1 (AP-1)-, CCAAT/enhancer-binding protein
(C/EBP)-, and nuclear factor-kappaB (NF-kappaB)-driven promoters in EBC-1 cells.
An electrophoretic mobility shift assay showed that serralysin activates the
binding of AP-1, C/EBPbeta, and NF-kappaB in the cells. Inactivation of
serralysin resulted in the failure of transactivation of AP-1-, C/EBP-, and NF
kappaB-driven promoters in the cells. Furthermore, serralysin activated AP-1-,
C/EBP-, and NF-kappaB-driven promoters via PAR-2 in HeLa cells. PAR-2 antagonist
peptides decreased serralysin-induced transactivation of AP-1-, C/EBP-, and NF
kappaB-driven promoters in EBC-1 cells. Considered together, these results
suggest that serralysin requires PAR-2 to activate the critical transcription
factors AP-1, C/EBPbeta, and NF-kappaB for host inflammatory responses.
PMID- 17043107
TI - High levels of CXCL10 are produced by intestinal epithelial cells in AIDS
patients with active cryptosporidiosis but not after reconstitution of immunity.
AB - Chemokines play key roles in attracting immune cells to sites of infections.
However, few data on chemokine expression in the gut during human infections are
available. We examined expression of chemokines in intestinal tissues of AIDS
patients during active Cryptosporidium infection and during resolution of such an
infection. The chemokines and cytokines in cell lysates from jejunal biopsy
tissues were assayed by a 22-multiplex bead immunoassay. CXCL10 (IP-10) and its
receptor, CXCR3, in sections were studied by immunohistochemistry. In biopsies
from AIDS patients with active cryptosporidiosis, four chemokines (CXCL10, CCL11
[eotaxin], CCL5 [RANTES], and CCL2 [monocyte chemoattractant protein 1]) and
three cytokines (interleukin-1alpha [IL-1alpha], IL-10, and granulocyte colony
stimulating factor) were detected. The level of CXCL10 was significantly
increased in AIDS patients with cryptosporidiosis compared to the level in AIDS
patients without cryptosporidiosis or in normal volunteers (median in AIDS
patients with cryptosporidiosis, 508 pg/mg protein, compared to 111 pg/mg and 72
pg/mg protein in AIDS patients without cryptosporidiosis and in normal
volunteers, respectively [P < 0.05 and P < 0.005, respectively, as determined by
a Mann-Whitney test]). The level of CXCL10 correlated with the parasite burden
(as measured by the number of Cryptosporidium oocysts in the stools) and also
with the IL-1alpha concentration (Pearson correlation values, 0.961 [P < 0.01]
and 0.737 [P < 0.05]). As determined by immunohistochemistry, CXCL10 localized to
epithelial cells at the site of infection. Following effective antiparasite and
antiretroviral therapy, Cryptosporidium infections resolved, and the levels of
CXCL10 decreased to normal levels. We hypothesized that CXCL10 plays an important
role in the resolution of cryptosporidiosis by attracting immune effector cells
to the site of infection. By contrast, in AIDS patients lacking effector cells,
CXCL10 may contribute to the immunopathogenesis by recruiting inflammatory cells.
PMID- 17043108
TI - The activity and stability of the transcriptional coactivator p/CIP/SRC-3 are
regulated by CARM1-dependent methylation.
AB - The transcriptional coactivator p/CIP(SRC-3/AIB1/ACTR/RAC3) binds liganded
nuclear hormone receptors and facilitates transcription by directly recruiting
accessory factors such as acetyltransferase CBP/p300 and the coactivator arginine
methyltransferase CARM1. In the present study, we have established that
recombinant p/CIP (p300/CBP interacting protein) is robustly methylated by CARM1
in vitro but not by other protein arginine methyltransferase family members.
Metabolic labeling of MCF-7 breast cancer cells with S-adenosyl-L-[methyl
(3)H]methionine and immunoblotting using dimethyl arginine-specific antibodies
demonstrated that p/CIP is specifically methylated in intact cells. In addition,
methylation of full-length p/CIP is not supported by extracts derived from CARM1(
/-) mouse embryo fibroblasts, indicating that CARM1 is required for p/CIP
methylation. Using mass spectrometry, we have identified three CARM1-dependent
methylation sites located in a glutamine-rich region within the carboxy terminus
of p/CIP which are conserved among all steroid receptor coactivator proteins.
These results were confirmed by in vitro methylation of p/CIP using carboxy
terminal truncation mutants and synthetic peptides as substrates for CARM1.
Analysis of methylation site mutants revealed that arginine methylation causes an
increase in full-length p/CIP turnover as a result of enhanced degradation.
Additionally, methylation negatively impacts transcription via a second mechanism
by impairing the ability of p/CIP to associate with CBP. Collectively, our data
highlight coactivator methylation as an important regulatory mechanism in
hormonal signaling.
PMID- 17043110
TI - Drosophila dCBP is involved in establishing the DNA replication checkpoint.
AB - The CBP/p300 family of proteins comprises related acetyltransferases that
coactivate signal-responsive transcription. Recent evidence suggests that
p300/CBP may also interact directly with complexes that mediate different aspects
of DNA metabolism such as replication and repair. In this report, we show that
loss of dCBP in Drosophila cells and eye discs results in a defect in the cell
cycle arrest induced by stalled DNA replication. We show that dCBP and the
checkpoint kinase Mei-41 can be found together in a complex and, furthermore,
that dCBP has a genetic interaction with mei-41 in the response to stalled DNA
replication. These observations suggest a broader role for the p300/CBP
acetyltransferases in the modulation of chromatin structure and function during
DNA metabolic events as well as for transcription.
PMID- 17043109
TI - The protein arginine methyltransferase Prmt5 is required for myogenesis because
it facilitates ATP-dependent chromatin remodeling.
AB - Skeletal muscle differentiation requires the coordinated activity of
transcription factors, histone modifying enzymes, and ATP-dependent chromatin
remodeling enzymes. The type II protein arginine methyltransferase Prmt5
symmetrically dimethylates histones H3 and H4 and numerous nonchromatin proteins,
and prior work has implicated Prmt5 in transcriptional repression. Here we
demonstrate that MyoD-induced muscle differentiation requires Prmt5. One of the
first genes activated during differentiation encodes the myogenic regulator
myogenin. Prmt5 and dimethylated H3R8 (histone 3 arginine 8) are localized at the
myogenin promoter in differentiating cells. Modification of H3R8 required Prmt5,
and reduction of Prmt5 resulted in the abrogation of promoter binding by the Brg1
ATPase-associated with the SWI/SNF chromatin remodeling enzymes and all
subsequent events associated with gene activation, including increases in
chromatin accessibility and stable binding by MyoD. Prmt5 and dimethylated H3R8
were also associated with the myogenin promoter in activated satellite cells
isolated from muscle tissue, further demonstrating the physiological relevance of
these observations. The data indicate that Prmt5 facilitates myogenesis because
it is required for Brg1-dependent chromatin remodeling and gene activation at a
locus essential for differentiation. We therefore conclude that a histone
modifying enzyme is necessary to permit an ATP-dependent chromatin remodeling
enzyme to function.
PMID- 17043111
TI - The 6-fluoro-8-methoxy quinolone gatifloxacin down-regulates interleukin-8
production in prostate cell line PC-3.
AB - Fluoroquinolones exhibit immunomodulatory effects on monocytes and macrophages,
in addition to their bactericidal activities. It remains unknown even whether the
quinolones act directly on the prostate. This study was based on the
understanding of the molecular mechanisms of the actions of the fluoroquinolones
that can be used for the treatment of chronic prostatitis/chronic pelvic pain
syndrome. We investigated whether the 6-fluroro-8-methoxy quinolone gatifloxacin
(GFLX) affected the production and secretion of interleukin-8 (IL-8) in the
prostate cell line PC-3. GFLX decreased the level of IL-8 release from
unstimulated PC-3 cells. GFLX also attenuated IL-8 secretion from PC-3 cells
stimulated with peptidoglycan, Mycoplasma hominis, phorbol ester, and tumor
necrosis factor alpha (TNF-alpha), indicating that GFLX exhibits an anti
inflammatory effect on the prostate cell line. However, GFLX failed to alter
activation of the NF-kappaB and AP-1 elicited by these stimulants. GFLX
significantly attenuated the expression of IL-8 mRNA in TNF-alpha-stimulated PC-3
cells and down-regulated the transcriptional activity of the 5'-flanking region
of the IL-8 gene from -1481 to +44 bp. The deletion construct without the 5'
flanking region from -1481 to -170 bp but not the construct without the region
from -1481 to -188 bp reversed the suppressive effect of GFLX on IL-8 promoter
activity. These results demonstrate that GFLX suppresses IL-8 expression in the
prostate cell line by decreasing the promoter activity of the IL-8 gene.
PMID- 17043112
TI - Susceptibility of acinetobacter strains isolated from deployed U.S. military
personnel.
AB - The susceptibilities of 142 Acinetobacter baumannii-calcoaceticus complex
isolates (95 from wounded U.S. soldiers deployed overseas) to 13 antimicrobial
agents were determined by broth microdilution. The most active antimicrobial
agents (> or =95% of isolates susceptible) were colistin, polymyxin B, and
minocycline.
PMID- 17043113
TI - Hygromycin B inhibition of protein synthesis and ribosome biogenesis in
Escherichia coli.
AB - The aminoglycoside antibiotic hygromycin B was examined in Escherichia coli cells
for inhibitory effects on translation and ribosomal-subunit formation. Pulse
chase labeling experiments were performed, which verified lower rates of
ribosomal-subunit synthesis in drug-treated cells. Hygromycin B exhibited a
concentration-dependent inhibitory effect on viable-cell numbers, growth rate,
protein synthesis, and 30S and 50S subunit formation. Unlike other
aminoglycosides, hygromycin B was a more effective inhibitor of translation than
of ribosomal-subunit formation in E. coli. Examination of total RNA from treated
cells showed an increase in RNA corresponding to a precursor to the 16S rRNA,
while mature 16S rRNA decreased. Northern hybridization to rRNA in cells treated
with hygromycin B showed that RNase II- and RNase III-deficient strains of E.
coli accumulated 16S rRNA fragments upon treatment with the drug. The results
indicate that hygromycin B targets protein synthesis and 30S ribosomal-subunit
assembly.
PMID- 17043114
TI - Combination of multiplex PCRs for staphylococcal cassette chromosome mec type
assignment: rapid identification system for mec, ccr, and major differences in
junkyard regions.
AB - Staphylococcal cassette chromosome mec (SCCmec) typing, in combination with
genotyping of the Staphylococcus aureus chromosome, has become essential for
defining methicillin-resistant S. aureus (MRSA) clones in epidemiological
studies. We have developed a convenient system for SCCmec type assignment. The
system consists of six multiplex PCRs (M-PCRs) for identifying the ccr gene
complex (ccr), the mec gene complex (mec), and specific structures in the
junkyard (J) regions: M-PCR with primer set 1 (M-PCR 1) identified five types of
ccr genes; M-PCR 2 identified class A to class C mec; M-PCRs 3 and 4 identified
specific open reading frames in the J1 regions of type I and IV and of type II,
III, and V SCCmec elements, respectively; M-PCR 5 identified the transposons
Tn554 and PsiTn554 integrated into the J2 regions of type II and III SCCmec
elements; and M-PCR 6 identified plasmids pT181 and pUB110 integrated into J3
regions. The system was validated with 99 MRSA strains carrying SCCmec elements
of different types. The SCCmec types of 93 out of the 99 MRSA strains could be
assigned. The SCCmec type assignments were identical to those made with a PCR
system that uses numerous primer pairs to identify genes or gene alleles. Our
system of six M-PCRs is thus a convenient and reliable method for typing SCCmec
elements.
PMID- 17043115
TI - Effect of carbapenem administration on establishment of intestinal colonization
by vancomycin-resistant enterococci and Klebsiella pneumoniae in mice.
AB - In a mouse model, ertapenem inhibited the anaerobic intestinal microflora and
promoted overgrowth of enterococci, whereas imipenem-cilastatin had no effect on
the indigenous microflora. Ertapenem, but not imipenem-cilastatin, promoted
modest overgrowth of vancomycin-resistant enterococci when exposure occurred
during treatment. Neither agent promoted colonization with extended-spectrum beta
lactamase-producing Klebsiella pneumoniae.
PMID- 17043116
TI - Pharmacokinetics of intravenous linezolid in cerebrospinal fluid and plasma in
neurointensive care patients with staphylococcal ventriculitis associated with
external ventricular drains.
AB - The pharmacokinetic profile of linezolid in cerebrospinal fluid (CSF) in five
neurointensive care patients with staphylococcal ventriculitis was studied. The
mean area under concentration-time curve (+/- standard deviation) was 63 +/- 18.9
mg x h/liter, with a CSF-to-plasma ratio of 0.8 +/- 0.3. Times above MIC in CSF
were 99.8% and 57.2% for pathogens with MICs of 2 mg/liter and 4 mg/liter,
respectively.
PMID- 17043117
TI - Quinolone resistance in Helicobacter pylori isolates in Germany.
AB - We show that quinolone resistance in Helicobacter pylori has reached an alarming
level in Germany. Our data suggest that the use of quinolones requires prior
antimicrobial susceptibility testing, especially for isolates from patients who
have already undergone previous unsuccessful eradication treatments, and also
underline the further need for surveillance studies to monitor antibiotic
resistance in H. pylori.
PMID- 17043118
TI - Effect of anaerobic growth on quinolone lethality with Escherichia coli.
AB - Quinolone activity against Escherichia coli was examined during aerobic growth,
aerobic treatment with chloramphenicol, and anaerobic growth. Nalidixic acid,
norfloxacin, ciprofloxacin, and PD161144 were lethal for cultures growing
aerobically, and the bacteriostatic activity of each quinolone was unaffected by
anaerobic growth. However, lethal activity was distinct for each quinolone with
cells treated aerobically with chloramphenicol or grown anaerobically. Nalidixic
acid failed to kill cells under both conditions; norfloxacin killed cells when
they were grown anaerobically but not when they were treated with
chloramphenicol; ciprofloxacin killed cells under both conditions but required
higher concentrations than those required with cells grown aerobically; and
PD161144, a C-8-methoxy fluoroquinolone, was equally lethal under all conditions.
Following pretreatment with nalidixic acid, a shift to anaerobic conditions or
the addition of chloramphenicol rapidly blocked further cell death. Formation of
quinolone-gyrase-DNA complexes, observed as a sodium dodecyl sulfate (SDS)
dependent drop in cell lysate viscosity, occurred during aerobic and anaerobic
growth and in the presence and in the absence of chloramphenicol. However, lethal
chromosome fragmentation, detected as a drop in viscosity in the absence of SDS,
occurred with nalidixic acid treatment only under aerobic conditions in the
absence of chloramphenicol. With PD161144, chromosome fragmentation was detected
when the cells were grown aerobically and anaerobically and in the presence and
in the absence of chloramphenicol. Thus, all quinolones tested appear to form
reversible bacteriostatic complexes containing broken DNA during aerobic growth,
during anaerobic growth, and when protein synthesis is blocked; however, the
ability to fragment chromosomes and to rapidly kill cells under these conditions
depends on quinolone structure.
PMID- 17043119
TI - Sublethal concentrations of the aminoglycoside amikacin interfere with cell
division without affecting chromosome dynamics.
AB - Aminoglycosides bind to the 16S rRNA at the tRNA acceptor site (A site) and
disturb protein synthesis by inducing codon misreading. We investigated
Escherichia coli cell elongation and division, as well as the dynamics of
chromosome replication and segregation, in the presence of sublethal
concentrations of amikacin (AMK). The fates of the chromosome ori and ter loci
were monitored by visualization by using derivatives of LacI and TetR fused to
fluorescent proteins in E. coli strains that carry operator arrays at the
appropriate locations. The results showed that cultures containing sublethal
concentrations of AMK contained abnormally elongated cells. The chromosomes in
these cells were properly located, suggesting that the dynamics of replication
and segregation were normal. FtsZ, an essential protein in the process of cell
division, was studied by using an ectopic FtsZ-cyan fluorescent protein fusion.
Consistent with a defect in cell division, we revealed that the Z ring failed to
properly assemble in these elongated cells.
PMID- 17043120
TI - Activity of DX-619 compared to other agents against viridans group streptococci,
Streptococcus bovis, and Cardiobacterium hominis.
AB - Against 198 viridans group streptococci, 25 Streptococcus bovis strains, and 5
Cardiobacterium hominis strains, MICs of DX-619, a des-F(6)-quinolone, were
between 0.004 and 0.25 microg/ml. These MICs were lower than those of other
quinolones (< or = 0.008 to > 32 microg/ml). Beta-lactam MICs were between < or =
0.008 and 16 microg/ml. Azithromycin resistance was found in most species, while
most were telithromycin susceptible. Glycopeptides and linezolid were active
against viridans group strains but inactive against C. hominis.
PMID- 17043121
TI - Comparative bactericidal activities of daptomycin and vancomycin against
glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous GISA
isolates.
AB - Staphylococcus aureus strains from the U.S. SENTRY Antimicrobial Surveillance
Program, 2002-2003, glycopeptide-intermediate S. aureus (GISA) strains, and
heterogeneous GISA (hGISA) strains were used to compare bactericidal activities
of daptomycin and vancomycin using MICs and minimum bactericidal concentrations.
Glycopeptide-susceptible S. aureus and hGISA strains were further studied by
using time-kill curves. For all isolates, the daptomycin MIC50 and MIC90 are four
times lower and the log drops in viable counts at 6 h and 24 h are significantly
greater than those for vancomycin.
PMID- 17043122
TI - Combination of amphotericin B with flucytosine is active in vitro against
flucytosine-resistant isolates of Cryptococcus neoformans.
AB - The combination of flucytosine and amphotericin B was tested against 10
flucytosine-resistant isolates of Cryptococcus neoformans by checkerboard,
killing curves, and Etest. Although differences were observed depending on the
technique used, antagonism was never observed. The synergistic interaction was
related to the mechanism of flucytosine resistance of the isolates.
PMID- 17043123
TI - Pharmacokinetics of CS-023 (RO4908463), a novel parenteral carbapenem, in healthy
male Caucasian volunteers.
AB - The CS-023 concentration in plasma after administration by infusion to healthy
volunteers at a dose of 700 mg was decreased, with a half-life of 1.7 h, and the
cumulative urinary excretion was 59.4% of the dose. The total clearance, renal
clearance, and volume of distribution were 8.12 liters/h, 4.14 liters/h, and 17.2
liters, respectively.
PMID- 17043124
TI - Molecular characteristics and in vitro susceptibility to antimicrobial agents,
including the des-fluoro(6) quinolone DX-619, of Panton-Valentine leucocidin
positive methicillin-resistant Staphylococcus aureus isolates from the community
and hospitals.
AB - Highly virulent, community-acquired methicillin-resistant Staphylococcus aureus
(MRSA) strains with Panton-Valentine leucocidin (PVL) genes have been found
increasingly worldwide. Among a total of 2,101 MRSA strains isolated from
patients in hospitals in Japan, two were positive for PVL genes. One strain was
identified as a community-acquired MRSA strain with genotype sequence type 30
(ST30) and spa (staphylococcal protein A gene) type 19 from Japan and was
resistant only to beta-lactam antimicrobial agents. The other strain was closely
related to PVL+ multidrug-resistant, hospital-acquired MRSA strains (ST30, spa
type 43) derived from nosocomial outbreaks in the 1980s to 1990s in Japan but
with a divergent sequence type, ST765 (a single-locus variant of ST30). Twenty
two PVL+ MRSA strains, including those from Japan and those from other countries
with various sequence types (ST1, ST8, ST30, ST59, and ST80) and genotypes, were
examined for susceptibility to 31 antimicrobial agents. Among the agents, DX-619,
a des-fluoro(6) quinolone, showed the greatest activity, followed by rifampin and
sitafloxacin, a fluoroquinolone. The data suggest that DX-619 exhibits a superior
activity against PVL+ MRSA strains with various virulence genetic traits from the
community as well as from hospitals.
PMID- 17043125
TI - Phenotypic and molecular analysis of penicillin-nonsusceptible Streptococcus
pneumoniae isolates in Poland.
AB - beta-Lactams are the drugs of choice for the treatment of infections caused by
the important bacterial pathogen Streptococcus pneumoniae. The recent growth of
resistance of this organism to penicillin observed worldwide is of the highest
concern. In this study, using 887 surveillance pneumococcal isolates recovered in
Poland from 1998 to 2002, we observed the increase in penicillin
nonsusceptibility from 8.7% to 20.3%. All of the 109 penicillin-nonsusceptible S.
pneumoniae (PNSP) isolates identified, together with 22 archival PNSP isolates
from 1995 to 1997, were subsequently analyzed by susceptibility testing,
serotyping, profiling of pbp genes, pulsed-field gel electrophoresis, and
multilocus sequence typing (MLST). Four predominant serotypes, serotypes 6B, 9V,
14, and 23F, characterized 85.5% of the isolates. MLST revealed the presence of
34 sequence types, 15 of which were novel types. Representatives of seven
multiresistant international clones (Spain(23F)-1, Spain(6B)-2, Spain(9V)-3,
Taiwan(23F)-15, Poland(23F)-16, Poland(6B)-20, and Sweden(15A)-25) or their
closely related variants comprised the majority of the study isolates. The spread
of Spain(9V)-3 and its related clone of serotype 14/ST143 has remarkably
contributed to the recent increase in penicillin resistance in pneumococci in the
country.
PMID- 17043126
TI - Acyl-substituted dermaseptin S4 derivatives with improved bactericidal
properties, including on oral microflora.
AB - The 15-mer dermaseptin S4 derivative S4(1-15) was recently shown to exhibit
potent activity against oral pathogens associated with caries and periodontitis.
Here, we investigated possible modes for improving the peptide's properties
through systematic replacement of an N-terminal amino acid(s) with various fatty
acids that modulate the peptide's hydrophobicity and/or charge. Deletion of 1 to
3 residues led to progressive loss of potency as assessed by MIC experiments
performed on four test bacteria. Replacing the deleted amino acids with fatty
acids most often resulted in potency recovery or improvement, as evidenced by
lower MICs and faster bactericidal kinetics in culture media. Best results were
obtained after replacement of the N-terminal dipeptide alanine-leucine with
heptanoic (C7) or aminododecanoic (NC12) acid. Circular dichroism analysis
correlated antibacterial properties to the peptide's secondary structure. MIC
experiments and confocal laser scanning microscopy results indicated that C7-S4(3
15) and NC12-S4(3-15) were bactericidal to various oral pathogens, including
those which are immobilized in a biofilm. C7-S4(3-15) performed similarly to or
better than (depending on growth medium) IB-367, a peptide assessed in clinical
trials for treatment of oral mucositis, reducing CFU counts by >3 log units
within 2 min of incubation. Collectively, the data indicate that substitution of
fatty acids for amino acids may be a useful strategy in revealing improved
derivatives of known antimicrobial peptides and suggest the suitability of such
compounds for controlling pathogens associated with oral diseases.
PMID- 17043127
TI - Characterization of squalene epoxidase of Saccharomyces cerevisiae by applying
terbinafine-sensitive variants.
AB - Squalene epoxidase (SE) is the target of terbinafine, which specifically inhibits
the fungal enzyme in a noncompetitive manner. On the basis of functional
homologies to p-hydroxybenzoate hydroxylase (PHBH) from Pseudomonas fluorescens,
the Erg1 protein contains two flavin adenine dinucleotide (FAD) domains and one
nucleotide binding (NB) site. By in vitro mutagenesis of the ERG1 gene, which
codes for the Saccharomyces cerevisiae SE, we isolated erg1 alleles that
conferred increased terbinafine sensitivity or that showed a lethal phenotype
when they were expressed in erg1-knockout strain KLN1. All but one of the amino
acid substitutions affected conserved FAD/nucleotide binding sites. The G(25)S,
D(335)X (W, F, P), and G(210)A substitutions in the FADI, FADII, and NB sites,
respectively, rendered the SE variants nonfunctional. The G(30)S and L(37)P
variants exhibited decreased enzymatic activity, accompanied by a sevenfold
increase in erg1 mRNA levels and an altered sterol composition, and rendered KLN1
more sensitive not only to allylamines (10 to 25 times) but also to other
ergosterol biosynthesis inhibitors. The R(269)G variant exhibited moderately
reduced SE activity and a 5- to 10-fold increase in allylamine sensitivity but no
cross-sensitivity to the other ergosterol biosynthesis inhibitors. To further
elucidate the roles of specific amino acids in SE function and inhibitor
interaction, a homology model of Erg1p was built on the basis of the crystal
structure of PHBH. All experimental data obtained with the sensitive Erg1
variants support this model. In addition, the amino acids responsible for
terbinafine resistance, although they are distributed along the sequence of
Erg1p, cluster on the surface of the Erg1p model, giving rise to a putative
binding site for allylamines.
PMID- 17043128
TI - Multidrug resistance conferred by novel DNA polymerase mutations in human
cytomegalovirus isolates.
AB - The emergence of antiviral-resistant cytomegalovirus (CMV) strains is a
continuing clinical problem, with increased numbers of immunocompromised patients
given longer-duration antiviral prophylaxis. Two previously unrecognized CMV DNA
polymerase mutations (N408K and A834P) identified separately and together in at
risk lung and kidney transplant recipients and a third mutation (L737M)
identified in a liver transplant recipient were characterized by marker transfer
to antiviral-sensitive laboratory strains AD169 and Towne. Subsequent phenotypic
analyses of recombinant strains demonstrated the ability of mutation N408K to
confer ganciclovir (GCV) and cidofovir (CDV) resistance and of mutation A834P to
confer GCV, foscarnet, and CDV resistance. Mutation L737M did not confer
resistance to any of the antiviral agents tested. A recombinant strain containing
both N408K and A834P demonstrated increased GCV and CDV resistance compared to
the levels of resistance of the virus containing only the A834P mutation. The
addition of mutation N408K in combination with A834P also partially reconstituted
the replication impairment of recombinant virus containing only A834P. This
suggests that perturbation of both DNA polymerization (A834P) and exonuclease
(N408K) activities contributes to antiviral resistance and altered replication
kinetics in these mutant strains. The identification of these multidrug-resistant
CMV strains in at-risk seronegative recipients of organs from seropositive donors
suggests that improved prophylactic and treatment strategies are required. The
additive effect of multiple mutations on antiviral susceptibility suggests that
increasing antiviral-resistant phenotypes can result from different virus
antiviral interactions.
PMID- 17043129
TI - Clonal spread of macrolide- and tetracycline-resistant [erm(A) tet(O)] emm77
Streptococcus pyogenes isolates in Italy and Norway.
PMID- 17043130
TI - LfrR is a repressor that regulates expression of the efflux pump LfrA in
Mycobacterium smegmatis.
AB - The lfrA gene of Mycobacterium smegmatis encodes an efflux pump which mediates
resistance to different fluoroquinolones, cationic dyes, and anthracyclines. The
deletion of the lfrR gene, coding for a putative repressor and localized upstream
of lfrA, increased the lfrA expression. In this study, reverse transcription-PCR
experiments showed that the two genes are organized as an operon, and lacZ
reporter fusions were used to identify the lfrRA promoter region. The lfrRA
promoter assignment was verified by mapping the transcription start site by
primer extension. Furthermore, we found that some substrates of the multidrug
transporter LfrA, e.g., acriflavine, ethidium bromide, and rhodamine 123, enhance
lfrA expression at a detectable level of transcription. LfrR protein was purified
from Escherichia coli as a fusion protein with a hexahistidine tag and found to
bind specifically to a fragment 143 bp upstream of lfrR by gel shift analysis.
Furthermore, acriflavine was able to cause the dissociation of the LfrR from the
promoter, thus suggesting that this molecule interacts directly with LfrR,
inducing lfrA expression. These results suggest that the LfrR repressor is able
to bind to different compounds, which allows induction of LfrA multidrug efflux
pump expression in response to these ones. Together, all data suggest that the
LfrA pump is tightly regulated and that the repression and induction can be
switched about a critical substrate concentration which is toxic for the cell.
PMID- 17043131
TI - Contribution of target gene mutations and efflux to decreased susceptibility of
Salmonella enterica serovar typhimurium to fluoroquinolones and other
antimicrobials.
AB - The mechanisms involved in fluoroquinolone resistance in Salmonella enterica
include target alterations and overexpression of efflux pumps. The present study
evaluated the role of known and putative multidrug resistance efflux pumps and
mutations in topoisomerase genes among laboratory-selected and naturally
occurring fluoroquinolone-resistant Salmonella enterica serovar Typhimurium
strains. Strains with ciprofloxacin MICs of 0.25, 4, 32, and 256 microg/ml were
derived in vitro using serovar Typhimurium S21. These mutants also showed
decreased susceptibility or resistance to many nonfluoroquinolone antimicrobials,
including tetracycline, chloramphenicol, and several beta-lactams. The expression
of efflux pump genes acrA, acrB, acrE, acrF, emrB, emrD, and mdlB were
substantially increased (>or=2-fold) among the fluoroquinolone-resistant mutants.
Increased expression was also observed, but to a lesser extent, with three other
putative efflux pumps: mdtB (yegN), mdtC (yegO), and emrA among mutants with
ciprofloxacin MICs of >or=32 microg/ml. Deletion of acrAB or tolC in S21 and its
fluoroquinolone-resistant mutants resulted in increased susceptibility to
fluoroquinolones and other tested antimicrobials. In naturally occurring
fluoroquinolone-resistant serovar Typhimurium strains, deletion of acrAB or tolC
increased fluoroquinolone susceptibility 4-fold, whereas replacement of gyrA
double mutations (S83F D87N) with wild-type gyrA increased susceptibility>500
fold. These results indicate that a combination of topoisomerase gene mutations,
as well as enhanced antimicrobial efflux, plays a critical role in the
development of fluoroquinolone resistance in both laboratory-derived and
naturally occurring quinolone-resistant serovar Typhimurium strains.
PMID- 17043132
TI - Cardiac perforation 6 weeks after percutaneous atrial septal defect repair using
an Amplatzer septal occluder.
AB - A 14-year-old boy presented to the emergency department unaccompanied by his
parents with a decreased level of consciousness, bradycardia, and hypotension
after a syncopal episode. The patient's electronic chart revealed a percutaneous
closure of a secundum atrial septal defect using an Amplatzer septal occluder
(AGA Medical, Golden Valley, MN) 6 weeks before this presentation. An urgent
echocardiogram revealed a moderate pericardial effusion, and 320 mL of fresh
blood was evacuated by subxiphoid pericardiocentesis. The child underwent
surgical exploration and was found to have a perforation in the superior
posterior aspect of the right atrium, which was corrected. The septal occluder
was extracted, and the atrial septal defect was closed with a pericardial patch.
This case illustrates a rare but life-threatening complication of percutaneous
closure of atrial septal defect using an Amplatzer septal occluder and the
importance of timely access to patient records when available history and
physical examination are limited.
PMID- 17043134
TI - Systemic hyalinosis: a distinctive early childhood-onset disorder characterized
by mutations in the anthrax toxin receptor 2 gene (ANTRX2).
AB - OBJECTIVE: We sought to further characterize the phenotype and facilitate
clinical recognition of systemic hyalinosis in children who present with chronic
pain and progressive contractures in early childhood. PATIENTS AND METHODS: We
report on 3 children who presented in infancy with symptoms and signs that
initially were not recognized to be those of systemic hyalinosis. Although the
children were evaluated for a variety of problems, including lysosomal storage
disorders and nonaccidental trauma, all eventually underwent genetic analysis of
the anthrax toxin receptor 2 gene (ANTRX2) and were diagnosed as having systemic
hyalinosis. RESULTS: We describe the recognizable but variable clinical phenotype
of systemic hyalinosis and associated mutations in ANTRX2. Affected individuals
presented in early infancy with severe pain and progressive contractures. Initial
diagnostic evaluations were unrevealing; however, hyperpigmented skin over bony
prominences, skin nodules, and fleshy perianal masses suggested a diagnosis of
systemic hyalinosis. ANTRX2 analysis confirmed the diagnosis in each case.
Although 2 of the children died in infancy as a result of complications of
chronic diarrhea, the third child has survived into midchildhood. These data
suggest that some ANTRX2 mutations, such as that identified in the long-term
survivor, may be associated with a less severe course of disease. CONCLUSIONS:
Although some aspects of systemic hyalinosis may resemble lysosomal storage
disorders, the clinical features of systemic hyalinosis are distinctive, and
detection of an ANTRX2 mutation can confirm the diagnosis. Early recognition of
affected individuals should allow for aggressive pain control and expectant
management of the multiple associated problems, including gastrointestinal
dysfunction.
PMID- 17043133
TI - Reducing premature infants' length of stay and improving parents' mental health
outcomes with the Creating Opportunities for Parent Empowerment (COPE) neonatal
intensive care unit program: a randomized, controlled trial.
AB - OBJECTIVE: Although low birth weight premature infants and parents are at high
risk for adverse health outcomes, there is a paucity of studies that test early
NICU interventions with parents to prevent the development of negative parent
infant interaction trajectories and to reduce hospital length of stay. Our
objective was to evaluate the efficacy of an educational-behavioral intervention
program (ie, Creating Opportunities for Parent Empowerment) that was designed to
enhance parent-infant interactions and parent mental health outcomes for the
ultimate purpose of improving child developmental and behavior outcomes. DESIGN,
SETTING, AND PARTICIPANTS: A randomized, controlled trial was conducted with 260
families with preterm infants from 2001 to 2004 in 2 NICUs in the northeast
United States. Parents completed self-administered instruments during
hospitalization, within 7 days after infant discharge, and at 2 months' corrected
age. Blinded observers rated parent-infant interactions in the NICU.
INTERVENTION: All participants received 4 intervention sessions of audiotaped and
written materials. Parents in the Creating Opportunities for Parent Empowerment
program received information and behavioral activities about the appearance and
behavioral characteristics of preterm infants and how best to parent them. The
comparison intervention contained information regarding hospital services and
policies. MAIN OUTCOME MEASURES: Parental stress, depression, anxiety, and
beliefs; parent-infant interaction during the NICU stay; NICU length of stay; and
total hospitalization were measured. RESULTS: Mothers in the Creating
Opportunities for Parent Empowerment program reported significantly less stress
in the NICU and less depression and anxiety at 2 months' corrected infant age
than did comparison mothers. Blinded observers rated mothers and fathers in the
Creating Opportunities for Parent Empowerment program as more positive in
interactions with their infants. Mothers and fathers also reported stronger
beliefs about their parental role and what behaviors and characteristics to
expect of their infants during hospitalization. Infants in the Creating
Opportunities for Parent Empowerment program had a 3.8-day shorter NICU length of
stay (mean: 31.86 vs 35.63 days) and 3.9-day shorter total hospital length of
stay (mean: 35.29 vs 39.19 days) than did comparison infants. CONCLUSIONS: A
reproducible educational-behavioral intervention program for parents that
commences early in the NICU can improve parent mental health outcomes, enhance
parent-infant interaction, and reduce hospital length of stay.
PMID- 17043135
TI - Endosomes generate localized Rho-ROCK-MLC2-based contractile signals via Endo180
to promote adhesion disassembly.
AB - The regulated assembly and disassembly of focal adhesions and adherens junctions
contributes to cell motility and tumor invasion. Pivotal in this process is
phosphorylation of myosin light chain-2 (MLC2) by Rho kinase (ROCK) downstream of
Rho activation, which generates the contractile force necessary to drive
disassembly of epithelial cell-cell junctions and cell-matrix adhesions at the
rear of migrating cells. How Rho-ROCK-MLC2 activation occurs at these distinct
cellular locations is not known, but the emerging concept that endocytic dynamics
can coordinate key intracellular signaling events provides vital clues. We report
that endosomes containing the promigratory receptor Endo180 (CD280) can generate
Rho-ROCK-MLC2-based contractile signals. Moreover, we provide evidence for a
cellular mechanism in which Endo180-containing endosomes are spatially localized
to facilitate their contractile signals directly at sites of adhesion turnover.
We propose migration driven by Endo180 as a model for the spatial regulation of
contractility and adhesion dynamics by endosomes.
PMID- 17043136
TI - Protein tyrosine phosphatase TbPTP1: A molecular switch controlling life cycle
differentiation in trypanosomes.
AB - Differentiation in African trypanosomes (Trypanosoma brucei) entails passage
between a mammalian host, where parasites exist as a proliferative slender form
or a G0-arrested stumpy form, and the tsetse fly. Stumpy forms arise at the peak
of each parasitaemia and are committed to differentiation to procyclic forms that
inhabit the tsetse midgut. We have identified a protein tyrosine phosphatase
(TbPTP1) that inhibits trypanosome differentiation. Consistent with a tyrosine
phosphatase, recombinant TbPTP1 exhibits the anticipated substrate and inhibitor
profile, and its activity is impaired by reversible oxidation. TbPTP1
inactivation in monomorphic bloodstream trypanosomes by RNA interference or
pharmacological inhibition triggers spontaneous differentiation to procyclic
forms in a subset of committed cells. Consistent with this observation,
homogeneous populations of stumpy forms synchronously differentiate to procyclic
forms when tyrosine phosphatase activity is inhibited. Our data invoke a new
model for trypanosome development in which differentiation to procyclic forms is
prevented in the bloodstream by tyrosine dephosphorylation. It may be possible to
use PTP1B inhibitors to block trypanosomatid transmission.
PMID- 17043137
TI - Dynamic subcompartmentalization of the mitochondrial inner membrane.
AB - The inner membrane of mitochondria is organized in two morphologically distinct
domains, the inner boundary membrane (IBM) and the cristae membrane (CM), which
are connected by narrow, tubular cristae junctions. The protein composition of
these domains, their dynamics, and their biogenesis and maintenance are poorly
understood at the molecular level. We have used quantitative immunoelectron
microscopy to determine the distribution of a collection of representative
proteins in yeast mitochondria belonging to seven major processes: oxidative
phosphorylation, protein translocation, metabolite exchange, mitochondrial
morphology, protein translation, iron-sulfur biogenesis, and protein degradation.
We show that proteins are distributed in an uneven, yet not exclusive, manner
between IBM and CM. The individual distributions reflect the physiological
functions of proteins. Moreover, proteins can redistribute between the domains
upon changes of the physiological state of the cell. Impairing assembly of
complex III affects the distribution of partially assembled subunits. We propose
a model for the generation of this dynamic subcompartmentalization of the
mitochondrial inner membrane.
PMID- 17043138
TI - SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the
mammalian ER.
AB - Protein quality control in the endoplasmic reticulum (ER) involves recognition of
misfolded proteins and dislocation from the ER lumen into the cytosol, followed
by proteasomal degradation. Viruses have co-opted this pathway to destroy
proteins that are crucial for host defense. Examination of dislocation of class I
major histocompatibility complex (MHC) heavy chains (HCs) catalyzed by the human
cytomegalovirus (HCMV) immunoevasin US11 uncovered a conserved complex of the
mammalian dislocation machinery. We analyze the contributions of a novel complex
member, SEL1L, mammalian homologue of yHrd3p, to the dislocation process.
Perturbation of SEL1L function discriminates between the dislocation pathways
used by US11 and US2, which is a second HCMV protein that catalyzes dislocation
of class I MHC HCs. Furthermore, reduction of the level of SEL1L by small hairpin
RNA (shRNA) inhibits the degradation of a misfolded ribophorin fragment (RI332)
independently of the presence of viral accessories. These results allow us to
place SEL1L in the broader context of glycoprotein degradation, and imply the
existence of multiple independent modes of extraction of misfolded substrates
from the mammalian ER.
PMID- 17043139
TI - Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes.
AB - A mutation in the small GTPase Rab38 gives rise to the mouse coat color phenotype
"chocolate" (cht), implicating Rab38 in the regulation of melanogenesis. However,
its role remains poorly characterized. We report that cht Rab38(G19V) is inactive
and that the nearly normal pigmentation in cht melanocytes results from
functional compensation by the closely related Rab32. In cht cells treated with
Rab32-specific small interfering RNA, a dramatic loss of pigmentation is
observed. In addition to mature melanosomes, Rab38 and Rab32 localize to
perinuclear vesicles carrying tyrosinase and tyrosinase-related protein 1,
consistent with a role in the intracellular sorting of these proteins. In
Rab38/Rab32-deficient cells, tyrosinase appears to be mistargeted and degraded
after exit from the trans-Golgi network (TGN). This suggests that Rab38 and Rab32
regulate a critical step in the trafficking of melanogenic enzymes, in
particular, tyrosinase, from the TGN to melanosomes. This work identifies a key
role for the Rab38/Rab32 subfamily of Rab proteins in the biogenesis of
melanosomes and potentially other lysosome-related organelles.
PMID- 17043140
TI - Membranes of the world unite!
AB - Despite diverse origins, cellular fusion mechanisms converge at a pathway of
phospholipid bilayer fusion. In this mini-review, we discuss how proteins can
mediate each of the three major stages in the fusion pathway: contact,
hemifusion, and the opening of an expanding fusion pore.
PMID- 17043141
TI - Darkness descends with two Rabs.
AB - Over 60 distinct Rab GTPases regulate specific vesicular transport steps in the
mammalian central vacuolar system. Wasmeier et al. (this issue, p. 271) reveal a
redundant role for two tissue-specific Rab proteins in regulating transport to a
tissue-specific lysosome-related organelle, the melanosome.
PMID- 17043142
TI - Growth control by EGF repeats of the C. elegans Fibulin-1C isoform.
AB - Fibulin is a broadly conserved component of the extracellular matrix (ECM).
Previous studies have shown that Caenorhabditis elegans FIBULIN-1 (FBL-1)
controls the width of the gonad (Hesselson, D., C. Newman, K.W. Kim, and J.
Kimble. 2004. Curr. Biol. 14:2005-2010; Kubota, Y., R. Kuroki, and K. Nishiwaki.
2004. Curr. Biol. 14:2011-2018; Muriel, J.M., C. Dong, H. Hutter, and B.E. Vogel.
2005. Development. 132: 4223-4234). In this study, we report that FBL-1 also
controls developmental growth and that one isoform of fibulin-1, called FBL-1C,
controls both functions by distinct mechanisms. A large FBL-1C fragment,
including both epidermal growth factor (EGF) and fibulin-type C domains, is
responsible for constraining gonadal width, but a much smaller fragment
containing only two complete EGF repeats (EGF1-2C+) is critical for developmental
growth. We suggest that the larger fragment serves a scaffolding function to
stabilize the basement membrane and that the smaller fragment provides a
regulatory function at the cell surface or within the ECM to control growth.
PMID- 17043143
TI - T cell receptor for antigen induces linker for activation of T cell-dependent
activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2.
AB - Adaptor proteins positively or negatively regulate the T cell receptor for
antigen (TCR) signaling cascade. We report that after TCR stimulation, the
inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are
involved in a multimolecular complex including the lipid phosphatase Src homology
2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP)-1 and Grb-2
which interacts with the membrane signaling scaffold linker for activation of T
cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored
recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative
control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the
view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback
loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a
critical role in shaping the immune response and as gatekeepers for T cell
tolerance.
PMID- 17043144
TI - Triggering CD40 on endothelial cells contributes to tumor growth.
AB - Inflammatory cells can either promote or inhibit tumor growth. Here we studied
whether CD40, a key molecule for adaptive immune response, has any role in
mammary carcinogenesis of BALB/NeuT transgenic tumor-prone mice. We transferred
the HER2/neu oncogene into CD40-null background to obtain the CD40-KO/NeuT
strain. CD40-KO/NeuT mice showed delayed tumor onset and reduced tumor
multiplicity. BM (BM) transplantation experiments excluded a role of BM-derived
cells in the reduced tumorigenicity associated with CD40 deficiency. Rather, CD40
expressed by endothelial cells (ECs) takes part to the angiogenic process.
Accordingly, large vessels, well organized around the tumor lobular structures,
characterize BALB/NeuT tumors, whereas tiny numerous vessels with scarce
extracellular matrix are dispersed in the parenchyma of poorly organized CD40
KO/NeuT tumors. Activated platelets, which may interact with and activate ECs,
are a possible source of CD40L. Their localization within tumor vessels prompted
the idea of treating BALB/NeuT and CD40-KO/NeuT mice chronically with the anti
platelet drug clopidogrel, known to inhibit platelet CD40L expression. Treatment
of BALB/NeuT mice reduced tumor growth to a level similar to CD40-deficient mice,
whereas CD40-KO/NeuT mice treated or not showed the same attenuated tumor
outgrowth, indicating that activated platelets are the likely source of CD40L in
this model. Collectively, these data point to a participation of CD40/CD40L in
the angiogenic processes associated with mammary carcinogenesis of BALB/NeuT
mice.
PMID- 17043145
TI - Follicular lymphoma-like B cells in healthy individuals: a novel intermediate
step in early lymphomagenesis.
AB - Follicular lymphoma is one of the most common adult lymphoma, and remains
virtually incurable despite its relatively indolent nature. t(14;18)(q32;q21)
translocation, the genetic hallmark and early initiating event of follicular
lymphoma (FL) pathogenesis, is also present at low frequency in the peripheral
blood of healthy individuals. It has long been assumed that in healthy
individuals t(14;18) is carried by circulating quiescent naive B cells, where its
oncogenic potential would be restrained. Here, we question this current view and
demonstrate that in healthy individuals, t(14;18) is actually carried by an
expanding population of atypical B cells issued from germinal centers, displaying
genotypic and phenotypic features of FL, and prone to constitute potent
premalignant FL niches. These findings strongly impact both on the current
understanding of disease progression and on the proper handling of t(14;18)
frequency in blood as a potential early biomarker for lymphoma.
PMID- 17043146
TI - Identification of 12/15-lipoxygenase as a suppressor of myeloproliferative
disease.
AB - Though Abl inhibitors are often successful therapies for the initial stages of
chronic myelogenous leukemia (CML), refractory cases highlight the need for novel
molecular insights. We demonstrate that mice deficient in the enzyme 12/15
lipoxygenase (12/15-LO) develop a myeloproliferative disorder (MPD) that
progresses to transplantable leukemia. Although not associated with dysregulation
of Abl, cells isolated from chronic stage 12/15-LO-deficient (Alox15) mice
exhibit increased activation of the phosphatidylinositol 3-kinase (PI3-K)
pathway, as indicated by enhanced phosphorylation of Akt. Furthermore, the
transcription factor interferon consensus sequence binding protein (ICSBP) is
hyperphosphorylated and displays decreased nuclear accumulation, translating into
increased levels of expression of the oncoprotein Bcl-2. The ICSBP defect,
exaggerated levels of Bcl-2, and prolonged leukemic cell survival associated with
chronic stage Alox15 MPD are all reversible upon treatment with a PI3-K
inhibitor. Remarkably, the evolution of Alox15 MPD to leukemia is associated with
additional regulation of ICSBP on an RNA level, highlighting the potential
usefulness of the Alox15 model for understanding the transition of CML to crisis.
Finally, 12/15-LO expression suppresses the growth of a human CML-derived cell
line. These data identify 12/15-LO as an important suppressor of MPD via its role
as a critical upstream effector in the regulation of PI3-K-dependent ICSBP
phosphorylation.
PMID- 17043147
TI - Giving blood: a new role for CD40 in tumorigenesis.
AB - CD40 was initially identified as a receptor expressed by B cells that is crucial
for inducing an effective adaptive immune response. CD40 was subsequently shown
to be expressed by endothelial cells and to promote angiogenesis. New data now
show that in tumor-prone transgenic mice, CD40-mediated neovascularization is
essential for early stage tumorigenicity. This suggests, at least in this mouse
model, that CD40 has an important role in the angiogenic process that is coupled
to carcinogenesis, a finding that could lead to novel therapeutic opportunities.
PMID- 17043148
TI - Thermodynamics of CFTR channel gating: a spreading conformational change
initiates an irreversible gating cycle.
AB - CFTR is the only ABC (ATP-binding cassette) ATPase known to be an ion channel.
Studies of CFTR channel function, feasible with single-molecule resolution,
therefore provide a unique glimpse of ABC transporter mechanism. CFTR channel
opening and closing (after regulatory-domain phosphorylation) follows an
irreversible cycle, driven by ATP binding/hydrolysis at the nucleotide-binding
domains (NBD1, NBD2). Recent work suggests that formation of an NBD1/NBD2 dimer
drives channel opening, and disruption of the dimer after ATP hydrolysis drives
closure, but how NBD events are translated into gate movements is unclear. To
elucidate conformational properties of channels on their way to opening or
closing, we performed non-equilibrium thermodynamic analysis. Human CFTR channel
currents were recorded at temperatures from 15 to 35 degrees C in inside-out
patches excised from Xenopus oocytes. Activation enthalpies(DeltaH(double
dagger)) were determined from Eyring plots. DeltaH(double dagger) was 117 +/- 6
and 69 +/- 4 kJ/mol, respectively, for opening and closure of partially
phosphorylated, and 96 +/- 6 and 73 +/- 5 kJ/mol for opening and closure of
highly phosphorylated wild-type (WT) channels. DeltaH(double dagger) for reversal
of the channel opening step, estimated from closure of ATP hydrolysis-deficient
NBD2 mutant K1250R and K1250A channels, and from unlocking of WT channels locked
open with ATP+AMPPNP, was 43 +/- 2, 39 +/- 4, and 37 +/- 6 kJ/mol, respectively.
Calculated upper estimates of activation free energies yielded minimum estimates
of activation entropies (DeltaS(double dagger)), allowing reconstruction of the
thermodynamic profile of gating, which was qualitatively similar for partially
and highly phosphorylated CFTR. DeltaS(double dagger) appears large for opening
but small for normal closure. The large DeltaH(double dagger) and DeltaS(double
dagger) (TDeltaS(double dagger) >/= 41 kJ/mol) for opening suggest that the
transition state is a strained channel molecule in which the NBDs have already
dimerized, while the pore is still closed. The small DeltaS(double dagger) for
normal closure is appropriate for cleavage of a single bond (ATP's beta-gamma
phosphate bond), and suggests that this transition state does not require large
scale protein motion and hence precedes rehydration (disruption) of the dimer
interface.
PMID- 17043149
TI - Cooperative gating between single HCN pacemaker channels.
AB - HCN pacemaker channels (I(f), I(q), or I(h)) play a fundamental role in the
physiology of many excitable cell types, including cardiac myocytes and central
neurons. While cloned HCN channels have been studied extensively in macroscopic
patch clamp experiments, their extremely small conductance has precluded single
channel analysis to date. Nevertheless, there remain fundamental questions about
HCN gating that can be resolved only at the single channel level. Here we present
the first detailed single channel study of cloned mammalian HCN2. Excised patch
clamp recordings revealed discrete hyperpolarization-activated, cAMP-sensitive
channel openings with amplitudes of 150-230 fA in the activation voltage range.
The average conductance of these openings was approximately 1.5 pS at -120 mV in
symmetrical 160 mM K(+). Some traces with multiple channels showed unusual gating
behavior, characterized by a variable long delay after a voltage step followed by
runs of openings. Noise analysis on macroscopic currents revealed fluctuations
whose magnitudes were systematically larger than predicted from the actual single
channel current size, consistent with cooperativity between single HCN channels.
PMID- 17043150
TI - Detection of the opening of the bundle crossing in KcsA with fluorescence
lifetime spectroscopy reveals the existence of two gates for ion conduction.
AB - The closed KcsA channel structure revealed a crossing of the cytosolic ends of
the transmembrane helices blocking the permeation pathway. It is generally agreed
that during channel opening this helical bundle crossing has to widen in order to
enable access to the inner cavity. Here, we address the question of whether the
opening of the inner gate is sufficient for ion conduction, or if a second gate,
located elsewhere, may interrupt the ion flow. We used fluorescence lifetime
measurements on KcsA channels labeled with tetramethylrhodamine at residues in
the C-terminal end of TM2 to report on the opening of the lower pore region. We
found two populations of channels with different fluorescence lifetimes, whose
relative distribution agrees with the open probability of the channel. The
absolute fraction of channels found with an open bundle crossing is too high to
explain the low open probability of the KcsA-WT channel. We found the same
distribution as in the WT channel between open and closed bundle crossing for two
KcsA mutants, A73E and E71A, which significantly increase open probability at low
pH. These two results strongly suggest that a second gate in the ion permeation
pathway exists. The location of the mutations A73E and E71A suggests that the
second gate may be the selectivity filter, which resides in an inactivated state
under steady-state conditions. Since the long closed times observed in KcsA-WT
are not present in KcsA-A73E or -E71A, we propose that KcsA-WT remains
predominantly in a state with an open bundle crossing but closed (inactivated)
second gate, while the mutations A73E and E71A sharply decrease the tendency to
enter in the inactivated state, and as a consequence, the second gate is
predominantly open at steady state. The ability to monitor the opening of the
bundle crossing optically enables the direct recording of the movement of the
pore helices while the channel is functioning.
PMID- 17043151
TI - Cross talk between activation and slow inactivation gates of Shaker potassium
channels.
AB - This study addresses the energetic coupling between the activation and slow
inactivation gates of Shaker potassium channels. To track the status of the
activation gate in inactivated channels that are nonconducting, we used two
functional assays: the accessibility of a cysteine residue engineered into the
protein lining the pore cavity (V474C) and the liberation by depolarization of a
Cs(+) ion trapped behind the closed activation gate. We determined that the rate
of activation gate movement depends on the state of the inactivation gate. A
closed inactivation gate favors faster opening and slower closing of the
activation gate. We also show that hyperpolarization closes the activation gate
long before a channel recovers from inactivation. Because activation and slow
inactivation are ubiquitous gating processes in potassium channels, the cross
talk between them is likely to be a fundamental factor in controlling ion flux
across membranes.
PMID- 17043152
TI - Positive charges at the intracellular mouth of the pore regulate anion conduction
in the CFTR chloride channel.
AB - Many different ion channel pores are thought to have charged amino acid residues
clustered around their entrances. The so-called surface charges contributed by
these residues can play important roles in attracting oppositely charged ions
from the bulk solution on one side of the membrane, increasing effective local
counterion concentration and favoring rapid ion movement through the channel.
Here we use site-directed mutagenesis to identify arginine residues contributing
important surface charges in the intracellular mouth of the cystic fibrosis
transmembrane conductance regulator (CFTR) Cl(-) channel pore. While wild-type
CFTR was associated with a linear current-voltage relationship with symmetrical
solutions, strong outward rectification was observed after mutagenesis of two
arginine residues (R303 and R352) located near the intracellular ends of the
fifth and sixth transmembrane regions. Current rectification was dependent on the
charge present at these positions, consistent with an electrostatic effect.
Furthermore, mutagenesis-induced rectification was more pronounced at lower Cl(-)
concentrations, suggesting that these mutants had a reduced ability to
concentrate Cl(-) ions near the inner pore mouth. R303 and R352 mutants exhibited
reduced single channel conductance, especially at negative membrane potentials,
that was dependent on the charge of the amino acid residue present at these
positions. However, the very low conductance of both R303E and R352E-CFTR could
be greatly increased by elevating intracellular Cl(-) concentration. Modification
of an introduced cysteine residue at position 303 by charged methanethiosulfonate
reagents reproduced charge-dependent effects on current rectification.
Mutagenesis of arginine residues in the second and tenth transmembrane regions
also altered channel permeation properties, however these effects were not
consistent with changes in channel surface charges. These results suggest that
positively charged arginine residues act to concentrate Cl(-) ions at the inner
mouth of the CFTR pore, and that this contributes to maximization of the rate of
Cl(-) ion permeation through the pore.
PMID- 17043154
TI - Concentration-dependent mode of interaction of angiotensin II receptor blockers
with uric acid transporter.
AB - Serum uric acid (SUA) is currently recognized as a risk factor for cardiovascular
disease. It has been reported that an angiotensin II receptor blocker (ARB),
losartan, decreases SUA level, whereas other ARBs, such as candesartan, have no
lowering effect. Because the renal uric acid transporter (URAT1) is an important
factor controlling the SUA level, we examined the involvement of URAT1 in those
differential effects of various ARBs on SUA level at clinically relevant
concentrations. This study was done by using URAT1-expressing Xenopus oocytes.
Losartan, pratosartan, and telmisartan exhibited cis-inhibitory effects on the
uptake of uric acid by URAT1, whereas at higher concentrations, only telmisartan
did, and these ARBs reduced the uptake in competitive inhibition kinetics. On the
other hand, candesartan, EXP3174 [2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5
yl)biphenyl-4-yI)methyl]imidazole-5-carboxylic acid] (a major metabolite of
losartan), olmesartan, and valsartan were not inhibitory. Preloading of those
ARBs in the oocytes enhanced the URAT1-mediated uric acid uptake, showing a trans
stimulatory effect. The present study is a first demonstration of the
differential effects of ARBs on URAT1 that some ARBs are both cis-inhibitory and
trans-stimulatory, depending on concentration, whereas others exhibit either a
trans-stimulatory or cis-inhibitory effect alone, which could explain the
clinically observed differential effects of ARBs on SUA level. Furthermore, it
was found that such differential effects of ARBs on URAT1 could be predicted from
the partial chemical structures of ARBs, which will be useful information for the
appropriate use and development of ARBs without an increase of SUA.
PMID- 17043155
TI - Valproic acid is not a substrate for P-glycoprotein or multidrug resistance
proteins 1 and 2 in a number of in vitro and in vivo transport assays.
AB - The antiepileptic drug valproic acid (VPA) is widely used in the treatment of
epilepsy, bipolar disorders, and migraine. However, rather high doses are
required for the clinical effects of VPA, which is due to its relatively
inefficient delivery to the brain. The poor brain distribution of VPA is thought
to reflect an asymmetric transport system at the blood-brain barrier (BBB). Based
on recent data from in vitro experiments, multidrug resistance proteins (MRPs)
have been proposed to be involved in the efflux transport of VPA at the BBB. In
the present study, we used different experimental in vitro and in vivo strategies
to evaluate whether VPA is a substrate for MRPs or the efflux transporter P
glycoprotein (Pgp). In contrast to known Pgp or MRP substrates, such as
cyclosporin A or vinblastine, no directional transport of VPA was observed in
cell monolayer efflux assays using the kidney cell lines Madin Darby canine
kidney II and LLC-PK1, which had been transfected with either human or mouse
cDNAs for the genes encoding Pgp, MRP1, or MRP2. Likewise, no indication for
efflux transport of VPA was obtained in a rat microdialysis model, using
inhibitors of either Pgp or MRPs. Furthermore, a significant role of MRP2 in
brain efflux of VPA was excluded by using MRP2-deficient rats. Our data do not
support the hypothesis that MRP1 or MRP2 is involved in the efflux of VPA from
the brain. Thus, the molecular identity of the putative transporter(s) mediating
the active efflux of VPA from the brain remains to be elucidated.
PMID- 17043156
TI - Atrial peptides modify the effect of marinobufagenin on sodium pumps:
implications for blood pressure control.
PMID- 17043158
TI - ANP differentially modulates marinobufagenin-induced sodium pump inhibition in
kidney and aorta.
AB - NaCl loading and plasma volume expansion stimulate 2 natriuretic systems,
vasoconstrictor, digitalis-like Na/K-ATPase inhibitors and vasorelaxant ANP
peptides. Several hormones, including ANP, regulate activity of the Na/K-ATPase
by modulation of its phosphorylation state. We studied effects of ANP on Na/K
ATPase phosphorylation and inhibition by an endogenous sodium pump ligand,
marinobufagenin, in the aorta and renal medulla from male Sprague-Dawley rats.
Marinobufagenin dose-dependently inhibited the Na/K-ATPase in renal and vascular
membranes at the level of higher (nanomolar) and lower affinity (micromolar)
binding sites. Marinobufagenin (1 nmol/L) inhibited Na/K-ATPase in aortic
sarcolemma (18%) and in renal medulla (19%). prepro-ANP 104 to 123 (ppANP) and
alpha-human ANP ([alpha-hANP] both 1 nmol/L) potentiated marinobufagenin-induced
Na/K-ATPase inhibition in the kidney, but reversed the effect of marinobufagenin
in the aorta. Similarly, ppANP and alpha-hANP modulated the sodium pump (ouabain
sensitive (86)Rb uptake) inhibitory effects of marinobufagenin in the aorta and
renal medulla. In renal medulla, ppANP and alpha-hANP induced alpha-1 Na/K-ATPase
phosphorylation, whereas in aorta, both peptides dephosphorylated Na/K-ATPase.
The effect of ppANP on Na/K-ATPase phosphorylation and inhibition was mimicked by
a protein kinase G activator, 8-Br-PET-cGMP (10 micromol/L), and prevented by a
protein kinase G inhibitor, KT5823 (60 nmol/L). Our results suggest that alpha-1
Na/K-ATPase inhibition by marinobufagenin in the kidney is enhanced via Na/K
ATPase phosphorylation by ANP, whereas in the aorta, ANP exerts an opposite
effect. The concurrent production of a vasorelaxant, ANP, and a vasoconstrictor,
marinobufagenin, potentiate each other's natriuretic effects, but ANP peptides
may offset the deleterious vasoconstrictor effect of marinobufagenin.
PMID- 17043157
TI - Angiotensin II induces interleukin-6 in humans through a mineralocorticoid
receptor-dependent mechanism.
AB - This study tested the hypothesis that angiotensin promotes oxidative stress and
inflammation in humans via aldosterone and the mineralocorticoid receptor. We
measured the effect of intravenous aldosterone (0.7 mug/kg per hour for 10 hours
followed by 0.9 mug/kg per hour for 4 hours) and vehicle in a randomized, double
blind crossover study in 11 sodium-restricted normotensive subjects. Aldosterone
increased interleukin (IL)-6 (from 4.7+/-4.9 to 9.4+/-7.1 pg/mL; F=4.94; P=0.04)
but did not affect blood pressure, serum potassium, or high-sensitivity C
reactive protein. We next conducted a randomized, double-blind, placebo
controlled, crossover study to measure the effect of 3-hour infusion of
angiotensin II (2 ng/kg per minute) and norepinephrine (30 ng/kg per minute) on
separate days after 2 weeks of placebo or spironolactone (50 mg per day) in 14
salt-replete normotensive subjects. Angiotensin II increased blood pressure
(increase in systolic pressure: 13.7+/-7.5 and 15.2+/-9.4 mm Hg during placebo
and spironolactone, respectively; P<0.001 for angiotensin II) and decreased renal
plasma flow (-202+/-73 and -167+/-112 mL/min/1.73 kg/m(2); P<0.001 for
angiotensin II effect) similarly during placebo and spironolactone.
Spironolactone enhanced the aldosterone response to angiotensin II (increase of
17.0+/-10.6 versus 9.0+/-5.7 ng/dL; P=0.002). Angiotensin II transiently
increased free plasma F(2)-isoprostanes similarly during placebo and
spironolactone. Angiotensin II increased serum IL-6 concentrations during placebo
(from 1.8+/-1.1 to 2.4+/-1.4 pg/mL; F=4.5; P=0.04) but spironolactone prevented
this effect (F=6.4; P=0.03 for spironolactone effect). Norepinephrine increased
blood pressure and F(2)-isoprostanes but not aldosterone or IL-6. Aldosterone
increases IL-6 in humans. These data suggest that angiotensin II induces IL-6
through a mineralocorticoid receptor-dependent mechanism in humans. In contrast,
angiotensin II-induced oxidative stress, as measured by F(2)-isoprostanes, is
mineralocorticoid receptor independent and may be pressor dependent.
PMID- 17043160
TI - Correlating ambulatory blood pressure measurements with arterial stiffness: a
conceptual inconsistency?
PMID- 17043161
TI - Cardiovascular effects of nonproteolytic activation of prorenin.
PMID- 17043162
TI - Exaggerated cardiovascular stress responses and impaired beta-adrenergic-mediated
pressor recovery in obese Zucker rats.
AB - Clinical studies have demonstrated that the pressor response to acute stress is
larger in obese versus lean individuals. We therefore tested the hypotheses that
the pressor response to behavioral stress is greater in obese (OZRs) versus lean
Zucker rats (LZRs) and that reduced beta-adrenergic-mediated vasodilation
contributes to the enhanced pressor response. Animals were restrained and
subjected to acute pulsatile air jet stress (3 minutes), followed by a poststress
period of 20 minutes; beta-adrenergic blockade was achieved with propranolol (5
mg/kg, IV) given 15 minutes before the start of air jet stress. Mean arterial
pressure (MAP) was continuously monitored by telemetry. Untreated OZRs responded
with a greater integrated pressor response (area under the curve [AUC]) to acute
stress (41.2+/-6.1 versus 21.2+/-3.3 mm Hgx3 minutes, OZR versus LZR; P<0.05) and
significantly reduced poststress recovery of MAP. Beta-adrenergic blockade had no
effect on stress AUC in either LZRs or OZRs but significantly attenuated the
poststress recovery of MAP in LZRs only (poststress AUC: -100.1+/-48.1 versus
49.0+/-13.5 mm Hgx20 minutes, untreated versus propranolol; P<0.05). In
anesthetized animals, significantly smaller increases in mesenteric vascular
conductance contributed to blunted depressor responses to isoproterenol in OZRs
versus LZRs, suggesting that beta-adrenergic stimulation causes a greater
reduction in total peripheral resistance in lean versus obese animals. We
conclude that beta-adrenergic-mediated vasodilation facilitates blood pressure
recovery after stress and that this pathway is compromised in an animal model of
morbid obesity, resulting in the impaired ability to regulate blood pressure
during stress.
PMID- 17043163
TI - CuZn superoxide dismutase deficiency: culprit of accelerated vascular aging
process.
PMID- 17043164
TI - Heterozygous CuZn superoxide dismutase deficiency produces a vascular phenotype
with aging.
AB - The goal of this study was to test the hypothesis that loss of a single copy of
the gene for CuZn superoxide dismutase (CuZnSOD) increases vascular superoxide
levels and produces vascular dysfunction with aging. Responses of carotid
arteries from young (7 months) and old (22 to 24 months of age) heterozygous
CuZnSOD-deficient (CuZnSOD(+/-)) mice and their wild-type (CuZnSOD(+/+))
littermates were examined in vitro. Total superoxide dismutase activity in aorta
was reduced by approximately 30% (P<0.05) in CuZnSOD(+/-) mice compared with wild
type mice. Responses to acetylcholine (an endothelium-dependent agonist) produced
relaxation that was similar (P>0.05) in carotid arteries from young wild-type,
young CuZnSOD(+/-), and old wild-type mice. In contrast, relaxation to
acetylcholine was markedly impaired in old CuZnSOD(+/-) mice (eg, 100 micromol/L
acetylcholine produced 51+/-5% and 96+/-5% relaxation in vessels from old
CuZnSOD(+/-) and old wild-type mice, respectively). This effect was selective,
because relaxation to nitroprusside (an endothelium-independent agonist) was not
affected by either CuZnSOD genotype or aging. The impaired response to
acetylcholine in old CuZnSOD(+/-) mice was restored toward normal with either
tempol (a scavenger of superoxide; 1 mmol/L) or PJ34 (an inhibitor of poly-ADP
ribose polymerase; 3 micromol/L). Vascular superoxide levels were increased in
aorta in old CuZnSOD(+/+) mice and increased further in CuZnSOD(+/-) mice with
aging. These findings provide the first direct evidence that normal CuZnSOD
expression protects endothelial function and that deficiency in a single copy of
the gene that encodes CuZnSOD produces increases in superoxide and marked
impairment of endothelial function with aging.
PMID- 17043166
TI - Activation of the cardiac proteasome during pressure overload promotes
ventricular hypertrophy.
AB - BACKGROUND: The adaptation of cardiac mass to hemodynamic overload requires an
adaptation of protein turnover, ie, the balance between protein synthesis and
degradation. We tested 2 hypotheses: (1) chronic left ventricular hypertrophy
(LVH) activates the proteasome system of protein degradation, especially in the
myocardium submitted to the highest wall stress, ie, the subendocardium, and (2)
the proteasome system is required for the development of LVH. METHODS AND
RESULTS: Gene and protein expression of proteasome subunits and proteasome
activity were measured separately from left ventricular subendocardium and
subepicardium, right ventricle, and peripheral tissues in a canine model of
severe, chronic (2 years) LVH induced by aortic banding and then were compared
with controls. Both gene and protein expressions of proteasome subunits were
increased in LVH versus control (P<0.05), which was accompanied by a significant
(P<0.05) increase in proteasome activity. Posttranslational modification of the
proteasome was also detected by 2-dimensional gel electrophoresis. These changes
were found specifically in left ventricular subendocardium but not in left
ventricular subepicardium, right ventricle, or noncardiac tissues from the same
animals. In a mouse model of chronic pressure overload, a 50% increase in heart
mass and a 2-fold increase in proteasome activity (both P<0.05 versus sham) were
induced. In that model, the proteasome inhibitor epoxomicin completely prevented
LVH while blocking proteasome activation. CONCLUSIONS: The increase in proteasome
expression and activity found during chronic pressure overload in myocardium
submitted to higher stress is also required for the establishment of LVH.
PMID- 17043167
TI - Long-term stimulation of adenosine A2b receptors begun after myocardial
infarction prevents cardiac remodeling in rats.
AB - BACKGROUND: Adenosine inhibits proliferation of cardiac fibroblasts and
hypertrophy of cardiomyocytes, both of which may play crucial roles in cardiac
remodeling. In the present study, we investigated whether chronic stimulation of
adenosine receptors begun after myocardial infarction (MI) prevents cardiac
remodeling. METHODS AND RESULTS: MI was produced in Wistar rats by permanent
ligation of the left anterior descending coronary artery. One week after the
onset of MI, animals were randomized into 8 groups: vehicle, dipyridamole (DIP;
the adenosine uptake inhibitor, 50 mg/kg), 2-chroloadenosine (CADO; the stable
analogue of adenosine, 2 mg/kg), and CADO in the presence of the nonselective
adenosine receptor antagonist 8-sulfophenyltheophylline (8-SPT) or the selective
antagonist for adenosine A1, A2a, A2b, or A3 receptor. Three weeks after
treatment, hemodynamic and echocardiographic parameters in the DIP and CADO
groups were significantly improved compared with the vehicle group. These
hemodynamic and echocardiographic improvements were blunted by either 8-SPT or
the selective adenosine A2b antagonist MRS1754 but not by the selective
antagonists for other subtypes of adenosine receptors. The collagen volume
fraction was smaller, and gene expression of the molecules associated with
cardiac remodeling such as matrix metalloproteinase in noninfarcted areas was
reduced in the DIP and CADO groups compared with the vehicle group, both of which
were attenuated by either 8-SPT or MRS1754. CONCLUSIONS: Long-term stimulation of
adenosine A2b receptors begun after MI attenuates cardiac fibrosis in the
noninfarcted myocardium and improves cardiac function. Drugs that stimulate
adenosine A2b receptors or increase adenosine levels are new candidates for
preventing cardiac remodeling after MI.
PMID- 17043168
TI - Transcriptional profiling in coronary artery disease: indications for novel
markers of coronary collateralization.
AB - BACKGROUND: The development of collateral circulation plays an important role in
protecting tissues from ischemic damage, and its stimulation has emerged as one
of principal approaches to therapeutic angiogenesis. Clinical observations have
documented substantial differences in the extent of collateralization among
patients with coronary artery disease (CAD), with some individuals demonstrating
marked abundance and others showing nearly complete absence of these vessels.
Recent studies have suggested that circulating monocytes play a major role in
collateral growth. The present study was undertaken to determine transcriptional
profiles of circulating monocytes in CAD patients with different extents of
collateral growth. METHODS AND RESULTS: Monocyte transcriptomes from CAD patients
with and without collateral vessels were obtained by use of high-throughput
expression profiling. Using a newly developed redundancy-based data mining
method, we have identified a set of molecular markers characteristic of a
"noncollateralgenic" phenotype. Moreover, we show that these transcriptional
abnormalities are independent of the severity of CAD or any other known clinical
parameter thought to affect collateral development and correlated with protein
expression levels in monocytes and plasma. CONCLUSIONS: Monocyte transcription
profiling identifies sets of patients with extensive versus poorly developed
collateral circulation. Thus, genetic factors may heavily influence coronary
collateral vessel growth in CAD and affect prognosis and response to therapeutic
interventions.
PMID- 17043169
TI - Short-term treatment with anti-CD3 antibody reduces the development and
progression of atherosclerosis in mice.
AB - BACKGROUND: Atherosclerosis is a chronic inflammatory disease of the large
arteries that is the primary cause of heart disease and stroke. Anti-CD3-specific
antibodies suppress immune responses by antigenic modulation of the CD3
antibody/T-cell receptor complex. Their unique capacity to restore self-tolerance
in a mouse model of diabetes and, importantly, in patients with recent-onset type
1 diabetes involves transforming growth factor-beta-dependent mechanisms via
expansion and/or activation of regulatory T cells. We hypothesized that treatment
with anti-CD3-specific antibodies might inhibit atherosclerosis development and
progression in mice. METHODS AND RESULTS: Low-density lipoprotein receptor
deficient mice were fed a high-cholesterol diet for 13 or 24 weeks. Anti-CD3
antibody was administered on 5 consecutive days beginning 1 week before or 13
weeks after the high-cholesterol diet was initiated, respectively. Control mice
were injected in parallel with phosphate-buffered saline. Anti-CD3 antibody
therapy reduced plaque development when administered before a high-cholesterol
diet and markedly decreased lesion progression in mice with already established
atherosclerosis. We found increased production of the antiinflammatory cytokine
transforming growth factor-beta in concanavalin A-stimulated lymph node cells and
enhanced expression of the regulatory T-cell marker Foxp3 in spleens of anti-CD3
antibody-treated mice. A higher percentage of apoptotic cells within the plaques
of anti-CD3 antibody-treated mice was also observed. CONCLUSIONS: Altered disease
progression, combined with the emergence of this particular cytokine pattern,
indicates that short-term treatment with an anti-CD3 antibody induces a
regulatory T-cell phenotype that restores self-tolerance in a mouse model of
atherosclerosis.
PMID- 17043170
TI - Images in cardiovascular medicine. Bilateral sinus of Valsalva aneurysms: an
extreme case.
PMID- 17043171
TI - Images in cardiovascular medicine. Takayasu's arteritis: the "macaroni sign".
PMID- 17043172
TI - Images in cardiovascular medicine. Vieussens' ring: combining computed tomography
coronary angiography and magnetic resonance imaging in assessing collateral
pathways.
PMID- 17043173
TI - Letter by Undas and Jakubowski regarding article, "Relationship between
homocysteine and mortality in chronic kidney disease".
PMID- 17043174
TI - A view from Cyprus.
PMID- 17043175
TI - Transvenous radiofrequency catheter ablation for atrial flutter and atrial
fibrillation: the end of the beginning?
PMID- 17043176
TI - Cardiac troponin: friend of the cardiac physician, foe to the cardiac patient?
PMID- 17043177
TI - Are drug-eluting stents cost-effective? It depends on whom you ask.
PMID- 17043178
TI - Drug-eluting stents: the price is not right.
PMID- 17043179
TI - A new terminology for left ventricular walls and location of myocardial infarcts
that present Q wave based on the standard of cardiac magnetic resonance imaging:
a statement for healthcare professionals from a committee appointed by the
International Society for Holter and Noninvasive Electrocardiography.
PMID- 17043180
TI - Successful treatment of mucous membrane pemphigoid with infliximab.
PMID- 17043181
TI - Aesthetic and functional efficacy of subcuticular running epidermal closures of
the trunk and extremity: a rater-blinded randomized control trial.
AB - OBJECTIVE: To ascertain whether subcuticular epidermal closures of elliptical
excisions of the trunk and extremities result in better functional and cosmetic
outcomes than simple running epidermal closures of the same sites. DESIGN:
Randomized controlled trial, with allocation of epidermal closure of elliptical
excisions to 4 arms, including 1 control arm (simple running polypropylene
sutures removed after 14 days) and 3 experimental arms (subcuticular running
polypropylene sutures removed after 14 days, subcuticular running polypropylene
sutures left in place, and subcuticular running polyglactin 910 sutures left in
place). All experimental interventions were preceded by deep dermal closure with
simple interrupted polyglactin 910 sutures. Interventions were delivered by 3
surgeons, who underwent 2 training sessions to minimize intersurgeon technique
variability. SETTING: Institutional referral practice providing ambulatory care
in an urban environment. PATIENTS: A consecutive sample of 36 adult patients
(ages 18-65 years), each referred for concurrent elliptical excision of at least
2 clinically atypical nevi of the trunk and/or extremity, were included in the
study. MAIN OUTCOME MEASURES: Primary outcome measures obtained at 3 and 9 months
included scar width in millimeters and blinded observer ordinal scale assessment
of overall scar appearance. Secondary outcome measures included ratings on the
standardized Vancouver Scar Scale and the Hollander Scar Scale; an additional
nonstandard item was added to assess pruritus. RESULTS: No difference among
groups was found in scar width at 3 or 9 months. Differences among groups were
detected in overall scar appearance (3 months, P<.001; 9 months, P<.001),
vascularity (3 months, P = .001; 9 months, P<.001), excessive distortion (3
months, P = .04; 9 months, P = .02), contour irregularity (3 months, P<.001), and
edge inversion (3 months, P = .01). The best overall appearance was with a
subcuticular running polyglactin 910 suture left in place, and the next best was
with a subcuticular running polypropylene suture left in place; differences
across groups persisted but decreased in intensity at 9 months. A secondary
analysis that matched high-tension anatomic sites (back and lower leg), and high
and moderate tension sites (also chest and shoulder) yielded the same main
effects and mostly the same results in pairwise comparisons. CONCLUSION: While
scar width does not appear to vary significantly based on choice of epidermal
closure, bilayered closures of the trunk and extremity have better overall
appearance and less associated erythema at 3 and 9 months after surgery with the
use of a subcuticular running polyglactin 910 suture left in place.
PMID- 17043182
TI - Factors influencing coexistence of toenail onychomycosis with tinea pedis and
other dermatomycoses: a survey of 2761 patients.
AB - OBJECTIVE: To evaluate the prevalence and factors influencing the presence of
concomitant dermatomycoses in patients with toenail onychomycosis. DESIGN:
Prospective study based on a specially designed questionnaire completed by
dermatologists. PATIENTS: A total of 2761 patients with toenail onychomycosis.
MAIN OUTCOME MEASURES: The diagnosis of fungal skin infections was confirmed by
direct microscopic examination or by culture. RESULTS: In 1181 patients (42.8%)
with toenail onychomycosis, concomitant fungal skin infections were noted. Tinea
pedis was the most common and was found in 933 patients (33.8%). Other
concomitant fungal skin infections were fingernail onychomycosis (7.4%), tinea
cruris (4.2%), tinea corporis (2.1%), tinea manuum (1.6%), and tinea capitis
(0.5%). The presence of concomitant fungal skin infections depended on number of
involved toenails; duration of onychomycosis; sex, age, and education level; area
of residence; and type of isolated fungus. CONCLUSIONS: The coexistence of
toenail onychomycosis with other types of fungal skin infections is a frequent
phenomenon. It could be hypothesized that infected toenails may be a site from
which the fungal infections could spread to other body areas. Effective therapy
for onychomycosis might therefore be essential not only to treat the lesional
toenails but also to prevent spreading the infection to other sites of the skin.
PMID- 17043183
TI - Skin and soft tissue infections due to rapidly growing mycobacteria: comparison
of clinical features, treatment, and susceptibility.
AB - OBJECTIVE: To compare the demographics, clinical features, susceptibility
patterns, and treatment for skin and soft tissue infections due to Mycobacterium
fortuitum and Mycobacterium chelonae or Mycobacterium abscessus. DESIGN:
Retrospective medical record review. SETTING: Mayo Clinic, Rochester, Minn.
PATIENTS: All patients seen at our institution with a positive culture for M
chelonae, M abscessus, or M fortuitum from skin or soft tissue sources between
January 1, 1987, and October 31, 2004. MAIN OUTCOME MEASURES: Patient
demographics, clinical characteristics, therapeutic data, microbiological data,
and outcomes. RESULTS: The medical records of 63 patients with skin or soft
tissue infections due to rapidly growing mycobacteria were reviewed. Patients
with M chelonae or M abscessus were older (61.5 vs 45.9 years, P<.001) and more
likely to be taking immunosuppressive medications (60% vs 17%, P = .002) than
patients with M fortuitum. Mycobacterium fortuitum tended to manifest as a single
lesion (89% vs 38%, P<.001), while most M chelonae or M abscessus manifested as
multiple lesions (62% vs 11%, P<.001). More patients with M fortuitum had a prior
invasive surgical procedure at the infected site (56% vs 27%, P = .04). Patients
with multiple lesions were more likely to be taking immunosuppressive medications
than those with single lesions (67% vs 30%, P = .006). Seven patients failed
treatment, several of whom were immunocompromised and had multiple comorbidities.
CONCLUSIONS: Skin and soft tissue infections due to rapidly growing mycobacteria
are associated with systemic comorbidities, including the use of
immunosuppressive medications. There are significant differences in the
demographic and clinical features of patients who acquire specific organisms,
including association with immunosuppression and surgical procedures.
PMID- 17043184
TI - Dermatologic adverse effects of lenalidomide therapy for amyloidosis and multiple
myeloma.
AB - OBJECTIVES: To examine dermatologic adverse effects of lenalidomide in patients
with amyloidosis and multiple myeloma and to determine whether the adverse
effects are different when lenalidomide is used alone compared with when it is
used in combination with dexamethasone. DESIGN: Retrospective review of medical
records. SETTING: Tertiary referral center. PATIENTS: Seventy-five patients with
multiple myeloma and 23 patients with amyloidosis participating in clinical
trials. INTERVENTION: In the 75 patients with multiple myeloma, lenalidomide was
the treatment in 24 and lenalidomide and dexamethasone in 51. In the 23 patients
with amyloidosis, lenalidomide was used alone. MAIN OUTCOME MEASURES: The
frequency, type, severity, and time of onset of all skin eruptions that were
temporally related to lenalidomide treatment were recorded. RESULTS: In the
patients with amyloidosis treated with lenalidomide, 10 (43%) had rashes. In the
patients with multiple myeloma, rashes occurred in 7 (29%) of those receiving
lenalidomide alone and in 15 (29%) of those receiving lenalidomide and
dexamethasone. The rashes were characterized as morbilliform, urticarial,
dermatitic, acneiform, and undefined. Severe rashes required permanent
discontinuation of lenalidomide therapy in 2 patients. In 23 patients (72%),
rashes occurred in the first month after therapy was initiated; however, delayed
onset rashes occurred in 9 (28%). CONCLUSIONS: The prevalence of dermatologic
adverse effects in patients receiving lenalidomide was higher in those with
amyloidosis than in those with multiple myeloma. The prevalence of skin eruptions
was not diminished by the concurrent use of systemic corticosteroids. Most skin
eruptions were mild and did not necessitate withdrawal of lenalidomide therapy.
PMID- 17043185
TI - Validity of beachgoers' self-report of their sun habits.
AB - OBJECTIVE: To examine the validity of beachgoers' self-reported sun protection
and UV exposure using objective measures. DESIGN: Eighty-eight participants
completed a brief survey when they arrived at the beach; their skin was swabbed
for the presence of sunscreen, while an observer recorded their clothing worn to
the beach and the presence of sunburn. On leaving the beach, an exit survey
detailing activities and sun habits while on the beach was completed by the
participants, follow-up sunscreen swabs were obtained, and sunburns were
recorded. Clothing observations were made for a subgroup (n = 25) of participants
during their beach stay. RESULTS: Most participants (38 [44%]) reported spending
2 to 3 hours at the beach, which was consistent with researcher observations
(Spearman rank correlation, r = 0.75). Moderate to substantial agreement was
achieved between reported use of sunscreen for the day and sunscreen swabs
(kappa, 0.54, 0.70, and 0.72 for the face, legs, and arms, respectively).
Participants' self-report of clothing worn to the beach had substantial agreement
with researcher observation: kappa coefficients ranged from 0.63 for footwear to
0.77 for head wear. Agreement was variable for clothing worn while on the beach,
with slight to fair agreement for sunglasses (kappa, 0.11) and footwear (kappa,
0.23) and substantial agreement for upper body clothing (kappa, 0.79). Agreement
between self-reported and observed sunburn was consistently lower (kappa, 0.21,
0.33, and 0.39 for the face, legs, and arms, respectively), with participants
reporting more sunburn on arrival than was observed. CONCLUSIONS: Overall, self
report measures of time outside, sunscreen use, and clothing worn demonstrated
good criterion validity when compared with observation and sunscreen swabbing.
Sunscreen swabbing proved an effective procedure for detecting sunscreen at a
beach setting.
PMID- 17043186
TI - African tick bite fever: a not-so-uncommon illness in international travelers.
AB - BACKGROUND: African tick bite fever is a rickettsial illness that has recently
emerged as a significant disease among international travelers. The vector is the
Amblyomma tick, which is endemic to sub-Saharan Africa and parts of the eastern
Caribbean. OBSERVATIONS: We describe a middle-aged woman who returned from a
mission trip to Zimbabwe with an influenzalike illness and inoculation eschar;
she also had a history of travel to a game farm. Biopsy revealed a
histopathologic pattern consistent with an infectious pathogenesis.
Immunohistochemical staining confirmed the presence of rickettsial organisms. In
light of the patient's history, the clinical constellation of signs and symptoms,
and the results of ancillary laboratory testing, a diagnosis of African tick bite
fever was made. The patient was treated with doxycycline hydrochloride and had an
uncomplicated course. CONCLUSIONS: This report further highlights the
epidemiological and clinical features of African tick bite fever. With the
increase in international travel, it is important to recognize the illness in
those who have been to endemic countries and to counsel patients regarding
preventive measures for planned travel.
PMID- 17043187
TI - Dermoscopy patterns of fibroepithelioma of pinkus.
AB - BACKGROUND: Fibroepithelioma of Pinkus (FeP) is a rare variant of basal cell
carcinoma that may clinically mimic a number of benign skin tumors. While the
dermoscopic features of basal cell carcinoma have been studied extensively,
little is known about the dermoscopic features of FeP. OBSERVATIONS:
Retrospective evaluation of clinical records and digital clinical dermoscopic
images of 10 histopathologically proved FePs (6 nonpigmented and 4 pigmented) was
performed. Clinically, no FeP was correctly identified and, in half of all
patients, a clinical differential diagnosis of purely benign skin lesions was
made. Dermoscopy enabled the correct diagnosis in 9 of 10 FePs, based on the
presence of fine arborizing vessels, either alone or associated with dotted
vessels, and white streaks (in 100%, 70%, and 90% of lesions, respectively). In
the 4 pigmented FePs, a structureless gray-brown area of pigmentation and
variable numbers of gray-blue dots were observed, in addition. CONCLUSIONS:
Dermoscopy is helpful in diagnosing FeP and in differentiating this variant of
basal cell carcinoma from other benign skin tumors commonly included in the
clinical differential diagnosis. This presumes, however, that dermoscopy is used
as a first-line examination for all skin lesions, not only for those that are
clinically suspect.
PMID- 17043188
TI - Antimicrobial allergy from polyvinyl chloride gloves.
AB - BACKGROUND: Contact allergy to plastic gloves is rare. Benzisothiazolinone is a
biocide that is mainly used in industrial settings. We first suspected delayed
type contact allergy to benzisothiazolinone from polyvinyl chloride (PVC) gloves
in 2004. We looked through our medical records from 1991 to 2005 to find similar
cases. OBSERVATIONS: We found a total of 8 patients who are allergic to
benzisothiazolinone and who had had exacerbations of their hand dermatitis while
using PVC gloves. Patch testing revealed that 3 of them had weak allergic or
doubtful reactions to the glove materials. Six of them had used Evercare Soft,
Medi-Point, or Derma Grip PVC gloves, which in chemical analysis were shown to
contain 9 to 32 ppm of benzisothiazolinone. Seven of the patients worked in
dentistry or health care and 1 in farming. All of them had had hand dermatitis
for many years. CONCLUSIONS: To our knowledge, there have been no previous
reports of contact allergy to antimicrobial agents in plastic gloves.
Benzisothiazolinone is widely used as a biocide in the manufacture of disposable
PVC gloves. Small amounts of benzisothiazolinone in the gloves may sensitize
those who already have hand dermatitis. We recommend that all patients with hand
dermatitis while using PVC gloves should be patch tested with
benzisothiazolinone.
PMID- 17043189
TI - Effect of topical vitamin D analogue on in vivo contact sensitization.
AB - BACKGROUND: The immunomodulatory role of vitamin D and its analogues has been
demonstrated in vitro and in vivo using animal models. We evaluated the effect of
a vitamin D analogue, calcipotriene, in vivo on human subjects using a contact
hypersensitivity model. OBSERVATIONS: Subjects were pretreated with topical
calcipotriene, simulated solar radiation, or both on buttock skin. They were then
sensitized and challenged using the contact allergen dinitrochlorobenzene. Immune
response was measured by change in skinfold thickness before vs after elicitation
across the challenge sites. CONCLUSIONS: Calcipotriene-treated individuals
demonstrated 64% immunosuppression compared with untreated controls. This is
equivalent to the immunosuppression induced by UV exposure.
PMID- 17043190
TI - Successful treatment of recalcitrant chronic idiopathic urticaria with
sulfasalazine.
AB - BACKGROUND: Antihistamines are the standard treatment for chronic idiopathic
urticaria (CIU). For patients whose urticaria is unresponsive to antihistamines,
the treatment options are limited. During the previous decade, there have been
several case reports demonstrating success with sulfasalazine therapy. In this
article, we present a case series evaluating sulfasalazine therapy for
antihistamine-unresponsive CIU. OBSERVATIONS: Nineteen patients with
antihistamine-unresponsive CIU were treated with sulfasalazine between 2002 and
2005. During sulfasalazine therapy, 14 patients (74%) reported significant
improvement, 4 patients (21%) reported minimal improvement but were not satisfied
with their symptom relief, and 1 patient (5%) reported a worsening of symptoms.
Of the 13 patients who required systemic steroids to control their urticaria, all
were able to reduce or discontinue steroid use during sulfasalazine therapy.
Although 7 patients (37%) had adverse effects (eg, nausea, headache, mild or
transient leukopenia, and transaminitis) that were thought to be caused by the
use of sulfasalazine, they all kept taking the drug. CONCLUSIONS: This case
series demonstrates that sulfasalazine can be a successful and safe treatment
option for patients with CIU who have not responded adequately to treatment with
antihistamines. Sulfasalazine was steroid sparing in all subjects who were
steroid dependent.
PMID- 17043191
TI - The pedal fungus reservoir.
PMID- 17043192
TI - Methods in skin cancer prevention: using a question-driven approach to guide the
choice of assessment approaches.
PMID- 17043193
TI - Purpuric nodule on the shoulder. Targetoid hemosiderotic hemangioma.
PMID- 17043194
TI - Bilateral lower eyelid masses. Orbital (intraorbital and extraocular) metastases
in breast cancer.
PMID- 17043195
TI - Painful plaque on a young man. Eccrine angiomatous hamartoma (EAH).
PMID- 17043196
TI - Multiple annular plaques in an infant. Neonatal lupus erythematosus (NLE).
PMID- 17043197
TI - Being a visual person: a dermatology residency interview perspective.
PMID- 17043198
TI - Electrical shavers as a possible risk factor for metal exposure.
PMID- 17043199
TI - Low but detectable serum levels of tacrolimus seen with the use of very dilute,
extemporaneously compounded formulations of tacrolimus ointment in the treatment
of patients with netherton syndrome.
PMID- 17043200
TI - To perform a biopsy or excise suspected actinic keratoses: another view.
PMID- 17043201
TI - Pimozide at least as safe and perhaps more effective than olanzapine for
treatment of Morgellons disease.
PMID- 17043202
TI - Adverse effects of cosmetic tattooing: an illustrative case of granulomatous
dermatitis following the application of permanent makeup.
PMID- 17043203
TI - Fever, episcleritis, epistaxis, and rash after safari holiday in Swaziland.
PMID- 17043204
TI - Metastatic hidradenocarcinoma: efficacy of capecitabine.
PMID- 17043205
TI - Leishmania major cutaneous leishmaniasis in HIV-positive patients does not spread
to extralesional sites.
PMID- 17043206
TI - Localized cutaneous sporotrichosis in a child.
PMID- 17043207
TI - A case of CD56+ mycosis fungoides.
PMID- 17043208
TI - Peristomal metastatic adenocarcinoma of the rectum.
PMID- 17043209
TI - Cyclosporine resolves generalized pustular psoriasis of pregnancy.
PMID- 17043210
TI - The significance of targetoid nevus.
PMID- 17043211
TI - Predicting complex biology with simple chemistry.
PMID- 17043212
TI - Smoking and lung cancer--a new role for an old toxicant?
PMID- 17043213
TI - Profile of Jacob N. Israelachvili.
PMID- 17043214
TI - Protective immunity to lethal challenge of the 1918 pandemic influenza virus by
vaccination.
AB - The remarkable infectivity and virulence of the 1918 influenza virus resulted in
an unprecedented pandemic, raising the question of whether it is possible to
develop protective immunity to this virus and whether immune evasion may have
contributed to its spread. Here, we report that the highly lethal 1918 virus is
susceptible to immune protection by a preventive vaccine, and we define its
mechanism of action. Immunization with plasmid expression vectors encoding
hemagglutinin (HA) elicited potent CD4 and CD8 cellular responses as well as
neutralizing antibodies. Antibody specificity and titer were defined by a
microneutralization and a pseudotype assay that could assess antibody specificity
without the need for high-level biocontainment. This pseudotype inhibition assay
can define evolving serotypes of influenza viruses and facilitate the development
of immune sera and neutralizing monoclonal antibodies that may help contain
pandemic influenza. Notably, mice vaccinated with 1918 HA plasmid DNAs showed
complete protection to lethal challenge. T cell depletion had no effect on
immunity, but passive transfer of purified IgG from anti-H1(1918) immunized mice
provided protective immunity for naive mice challenged with infectious 1918
virus. Thus, humoral immunity directed at the viral HA can protect against the
1918 pandemic virus.
PMID- 17043215
TI - Recruitment of CD63 to Cryptococcus neoformans phagosomes requires acidification.
AB - The subcellular localization of the cluster of differentiation 63 (CD63)
tetraspanin and its interaction with the class II MHC antigen presentation
pathway were examined in the context of phagocytosis by live cell imaging, by
using monomeric red fluorescent protein-tagged mouse CD63 expressed in primary
bone marrow-derived cell cultures. Upon phagocytosis of Cryptococcus neoformans
and polystyrene beads, CD63 was recruited selectively to C. neoformans-containing
phagosomes in a MyD88-independent acidification-dependent manner. Bead-containing
phagosomes, within a C. neoformans-containing cell, acidified to a lesser extent
and failed to recruit CD63 to a level detectable by microscopy. CD63 recruitment
to yeast phagosomes occurred independently of class II MHC and LAMP-1. These
observations indicate that the composition of distinct phagosomal compartments
within the same cell is determined by phagosomal cargo and may affect the outcome
of antigen processing and presentation.
PMID- 17043216
TI - Effect of force on mononucleosomal dynamics.
AB - Using single-molecule optical-trapping techniques, we examined the force-induced
dynamic behavior of a single nucleosome core particle. Our experiments using the
DNA construct containing the 601 nucleosome-positioning sequence revealed that
the nucleosome unravels in at least two major stages. The first stage, which we
attributed to the unraveling of the first DNA wrap around the histone octamer,
could be mechanically induced in a reversible manner, and when kept at constant
force within a critical force range, exhibited two-state hopping behavior. From
the hopping data, we determined the force-dependent equilibrium constant and
rates for opening/closing of the outer wrap. Our investigation of the second
unraveling event at various loading rates, which we attributed to the inner DNA
wrap, revealed that this unraveling event cannot be described as a simple two
state process. We also looked at the behavior of the mononucleosome in a high
salt buffer, which revealed that the outer DNA wrap is more sensitive to changes
in the ionic environment than the inner DNA wrap. These findings are needed to
understand the energetics of nucleosome remodeling.
PMID- 17043217
TI - erbB2 is required for G protein-coupled receptor signaling in the heart.
AB - erbB2/Her2, a ligandless receptor kinase, has pleiotropic effects on mammalian
development and human disease. The absence of erbB2 signaling in cardiac myocytes
results in dilated cardiomyopathy in mice, resembling the cardiotoxic effects
observed in a subset of breast cancer patients treated with the anti-Her2
antibody herceptin. Emerging evidence suggests that erbB2 is pivotal for
integrating signaling networks involving multiple classes of extracellular
signals. However, its role in G protein-coupled receptor (GPCR) signaling remains
undefined. Because the activation of the MAPK pathway through GPCR signaling is
important for cardiac homeostasis, we investigated whether erbB2 is required for
GPCR-mediated MAPK signaling in wild-type and heart-specific erbB2 mutant mice.
Here we demonstrate that erbB2, but not EGF receptor, is essential for MAPK
activation induced by multiple GPCR agonists in cardiac myocytes. erbB2 is
immunocomplexed with a GPCR in vivo and is transactivated after ligand treatment
in vitro. Coexpression of erbB2 with GPCRs in heterologous cells results in
ligand-dependent complex formation and MAPK activation. Furthermore, MAPK
activation and cardiac contractility are markedly impaired in heart-specific
erbB2 mutants infused with a GPCR agonist. These results reveal an essential
mechanism requiring erbB2 as a coreceptor for GPCR signaling in the heart. The
obligatory role of erbB2 in GPCR-dependent signaling may also be important in
other cellular systems.
PMID- 17043218
TI - The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with
RNA polymerase II.
AB - CDK8 (cyclin-dependent kinase 8), along with CycC, Med12, and Med13, form a
repressive module (the Cdk8 module) that prevents RNA polymerase II (pol II)
interactions with Mediator. Here, we report that the ability of the Cdk8 module
to prevent pol II interactions is independent of the Cdk8-dependent kinase
activity. We use electron microscopy and single-particle reconstruction to
demonstrate that the Cdk8 module forms a distinct structural entity that binds to
the head and middle region of Mediator, thereby sterically blocking interactions
with pol II.
PMID- 17043219
TI - An intramolecular folding sensor for imaging estrogen receptor-ligand
interactions.
AB - Strategies for high-throughput analysis of interactions between various hormones
and drugs with the estrogen receptor (ER) are crucial for accelerating the
understanding of ER biology and pharmacology. Through careful analyses of the
crystal structures of the human ER (hER) ligand-binding domain (hER-LBD) in
complex with different ligands, we hypothesized that the hER-LBD intramolecular
folding pattern could be used to distinguish ER agonists from selective ER
modulators and pure antiestrogens. We therefore constructed and validated
intramolecular folding sensors encoding various hER-LBD fusion proteins that
could lead to split Renilla/firefly luciferase reporter complementation in the
presence of the appropriate ligands. A mutant hER-LBD with low affinity for
circulating estradiol was also identified for imaging in living subjects. Cells
stably expressing the intramolecular folding sensors expressing wild-type and
mutant hER-LBD were used for imaging ligand-induced intramolecular folding in
living mice. This is the first hER-LBD intramolecular folding sensor suited for
high-throughput quantitative analysis of interactions between hER with hormones
and drugs using cell lysates, intact cells, and molecular imaging of small living
subjects. The strategies developed can also be extended to study and image other
important protein intramolecular folding systems.
PMID- 17043220
TI - UV irradiation induces a postreplication DNA damage checkpoint.
AB - Eukaryotic cells irradiated with high doses of UV exhibit cell-cycle responses
referred to as G(1)/S, intraS, and G(2)/M checkpoints. After a moderate UV dose
that approximates sunlight exposure and is lethal to fission yeast checkpoint
mutants, we found unexpectedly that these cell-cycle responses do not occur.
Instead, cells at all stages of the cell cycle carry lesions into S phase and
delay cell-cycle progression for hours after the completion of bulk DNA
synthesis. Both DNA replication and the checkpoint kinase, Chk1, are required to
generate this cell-cycle response. UV-irradiation of Deltachk1 cells causes
chromosome damage and loss of viability only after cells have replicated
irradiated DNA and entered mitosis. These data suggest that an important
physiological role of the cell-cycle response to UV is to provide time for
postreplication repair.
PMID- 17043221
TI - Unusual mechanical stability of a minimal RNA kissing complex.
AB - By using optical tweezers, we have investigated the mechanical unfolding of a
minimal kissing complex with only two G.C base pairs. The loop-loop interaction
is exceptionally stable; it is disrupted at forces ranging from 7 to 30 pN, as
compared with 14-20 pN for unfolding hairpins of 7 and 11 bp. By monitoring
unfolding/folding trajectories of single molecules, we resolved the
intermediates, measured their rate constants, and pinpointed the rate-limiting
steps. The two hairpins unfold only after breaking the intramolecular kissing
interaction, and the kissing interaction forms only after the folding of the
hairpins. At forces that favor the unfolding of the hairpins, the entire RNA
structure is kinetically stabilized by the kissing interaction, and extra work is
required to unfold the metastable hairpins. The strong mechanical stability of
even a minimal kissing complex indicates the importance of such loop-loop
interactions in initiating and stabilizing RNA dimers in retroviruses.
PMID- 17043222
TI - A rapid genome-scale response of the transcriptional oscillator to perturbation
reveals a period-doubling path to phenotypic change.
AB - Perturbation of the gated-synchrony system in yeast with phenelzine, an
antidepressant drug used in the treatment of affective disorders in humans, leads
to a rapid lengthening in the period of the genome-wide transcriptional
oscillation. The effect is a concerted, genome-scale change in expression that is
first seen in genes maximally expressed in the late-reductive phase of the cycle,
doubling the length of the reductive phase within two cycles after treatment.
Clustering of genes based on their temporal patterns of expression yielded just
three super clusters whose trajectories through time could then be mapped into a
simple 3D figure. In contrast to transcripts in the late-reductive phase, most
transcripts do not show transients in expression relative to others in their
temporal cluster but change their period in a concerted fashion. Mapping the
trajectories of the transcripts into low-dimensional surfaces that can be
represented by simple systems of differential equations provides a readily
testable model of the dynamic architecture of phenotype. In this system, period
doubling may be a preferred pathway for phenotypic change. As a practical matter,
low-amplitude, genome-wide oscillations, a ubiquitous but often unrecognized
attribute of phenotype, could be a source of seemingly intractable biological
noise in microarray studies.
PMID- 17043223
TI - Natural variation in Drosophila melanogaster diapause due to the insulin
regulated PI3-kinase.
AB - This study links natural variation in a Drosophila melanogaster overwintering
strategy, diapause, to the insulin-regulated phosphatidylinositol 3-kinase (PI3
kinase) gene, Dp110. Variation in diapause, a reproductive arrest, was associated
with Dp110 by using Dp110 deletions and genomic rescue fragments in transgenic
flies. Deletions of Dp110 increased the proportion of individuals in diapause,
whereas expression of Dp110 in the nervous system, but not including the visual
system, decreased it. The roles of phosphatidylinositol 3-kinase for both
diapause in D. melanogaster and dauer formation in Caenorhabditis elegans suggest
a conserved role for this kinase in both reproductive and developmental arrests
in response to environmental stresses.
PMID- 17043224
TI - Differential sensitivities of transcription factor target genes underlie cell
type-specific gene expression profiles.
AB - Changes in transcription factor levels and activities dictate developmental fate.
Such a change might affect the full ensemble of target genes for a factor or only
uniquely sensitive targets. We investigated the relationship among activity of
the hematopoietic transcription factor GATA-1, chromatin occupancy, and target
gene sensitivity. Graded activation of GATA-1 in GATA-1-null cells revealed high
, intermediate-, and low-sensitivity targets. GATA-1 activity requirements for
occupancy and transcription often correlated. A GATA-1 amino-terminal deletion
mutant severely deregulated the low-sensitivity gene Tac-2. Thus, cells
expressing different levels of a cell type-specific activator can have
qualitatively distinct target gene expression patterns, and factor mutations
preferentially deregulate low-sensitivity genes. Unlike other target genes, GATA
1-mediated Tac-2 regulation was bimodal, with activation followed by repression,
and the coregulator Friend of GATA-1 (FOG-1) selectively mediated repression. A
GATA-1 mutant defective in FOG-1 binding occupied a Tac-2 regulatory region at
levels higher than wild-type GATA-1, whereas FOG-1 facilitated chromatin
occupancy at a distinct target site. These results indicate that FOG-1 is a
determinant of GATA factor target gene sensitivity by either facilitating or
opposing chromatin occupancy.
PMID- 17043225
TI - An algorithm for assembly of ordered restriction maps from single DNA molecules.
AB - The restriction mapping of a massive number of individual DNA molecules by
optical mapping enables assembly of physical maps spanning mammalian and plant
genomes; however, not through computational means permitting completely de novo
assembly. Existing algorithms are not practical for genomes larger than lower
eukaryotes due to their high time and space complexity. In many ways, sequence
assembly parallels map assembly, so that the overlap-layout-consensus strategy,
recently shown effective in assembling very large genomes in feasible time, sheds
new light on solving map construction issues associated with single molecule
substrates. Accordingly, we report an adaptation of this approach as the formal
basis for de novo optical map assembly and demonstrate its computational
feasibility for assembly of very large genomes. As such, we discuss assembly
results for a series of genomes: human, plant, lower eukaryote and bacterial.
Unlike sequence assembly, the optical map assembly problem is actually more
complex because restriction maps from single molecules are constructed,
manifesting errors stemming from: missing cuts, false cuts, and high variance of
estimated fragment sizes; chimeric maps resulting from artifactually merged
molecules; and true overlap scores that are "in the noise" or "slightly above the
noise." We address these problems, fundamental to many single molecule
measurements, by an effective error correction method using global overlap
information to eliminate spurious overlaps and chimeric maps that are otherwise
difficult to identify.
PMID- 17043226
TI - Powering the planet: chemical challenges in solar energy utilization.
AB - Global energy consumption is projected to increase, even in the face of
substantial declines in energy intensity, at least 2-fold by midcentury relative
to the present because of population and economic growth. This demand could be
met, in principle, from fossil energy resources, particularly coal. However, the
cumulative nature of CO(2) emissions in the atmosphere demands that holding
atmospheric CO(2) levels to even twice their preanthropogenic values by
midcentury will require invention, development, and deployment of schemes for
carbon-neutral energy production on a scale commensurate with, or larger than,
the entire present-day energy supply from all sources combined. Among renewable
energy resources, solar energy is by far the largest exploitable resource,
providing more energy in 1 hour to the earth than all of the energy consumed by
humans in an entire year. In view of the intermittency of insolation, if solar
energy is to be a major primary energy source, it must be stored and dispatched
on demand to the end user. An especially attractive approach is to store solar
converted energy in the form of chemical bonds, i.e., in a photosynthetic process
at a year-round average efficiency significantly higher than current plants or
algae, to reduce land-area requirements. Scientific challenges involved with this
process include schemes to capture and convert solar energy and then store the
energy in the form of chemical bonds, producing oxygen from water and a reduced
fuel such as hydrogen, methane, methanol, or other hydrocarbon species.
PMID- 17043227
TI - Time scales of membrane fusion revealed by direct imaging of vesicle fusion with
high temporal resolution.
AB - Membrane fusion is a vital process of life involved, for example, in cellular
secretion via exocytosis, signaling between nerve cells, and virus infection. In
both the life sciences and bioengineering, controlled membrane fusion has many
possible applications, such as drug delivery, gene transfer, chemical
microreactors, or synthesis of nanomaterials. Until now, the fusion dynamics has
been elusive because direct observations have been limited to time scales that
exceed several milliseconds. Here, the fusion of giant lipid vesicles is induced
in a controlled manner and monitored with a temporal resolution of 50 micros. Two
different fusion protocols are used that are based on synthetic fusogenic
molecules and electroporation. For both protocols, the opening of the fusion
necks is very fast, with an average expansion velocity of centimeters per second.
This velocity indicates that the initial formation of a single fusion neck can be
completed in a few hundred nanoseconds.
PMID- 17043228
TI - Renal cortical cyclooxygenase 2 expression is differentially regulated by
angiotensin II AT(1) and AT(2) receptors.
AB - Macula densa cyclooxygenase 2 (COX-2)-derived prostaglandins serve as important
modulators of the renin-angiotensin system, and cross-talk exists between these
two systems. Cortical COX-2 induction by angiotensin-converting enzyme (ACE)
inhibitors or AT(1) receptor blockers (ARBs) suggests that angiotensin II may
inhibit cortical COX-2 by stimulating the AT(1) receptor pathway. In the present
studies we determined that chronic infusion of either hypertensive or
nonhypertensive concentrations of angiotensin II attenuated cortical COX-2.
Angiotensin II infusion reversed cortical COX-2 elevation induced by ACE
inhibitors. However, we found that angiotensin II infusion further stimulated
cortical COX-2 elevation induced by ARBs, suggesting a potential role for an
AT(2) receptor-mediated pathway when the AT(1) receptor was inhibited. Both WT
and AT(2) receptor knockout mice were treated for 7 days with either ACE
inhibitors or ARBs. Cortical COX-2 increased to similar levels in response to ACE
inhibition in both knockout and WT mice. In WT mice ARBs increased cortical COX-2
more than ACE inhibitors, and this stimulation was attenuated by the AT(2)
receptor antagonist PD123319. In the knockout mice ARBs led to significantly less
cortical COX-2 elevation, which was not attenuated by PD123319. PCR confirmed
AT(1a) and AT(2) receptor expression in the cultured macula densa cell line
MMDD1. Angiotensin II inhibited MMDD1 COX-2, and CGP42112A, an AT(2) receptor
agonist, stimulated MMDD1 COX-2. In summary, these results demonstrate that
macula densa COX-2 expression is oppositely regulated by AT(1) and AT(2)
receptors and suggest that AT(2) receptor-mediated cortical COX-2 elevation may
mediate physiologic effects that modulate AT(1)-mediated responses.
PMID- 17043229
TI - PGC-1alpha controls hepatitis B virus through nutritional signals.
AB - Hepatitis B virus (HBV) is a 3.2-kb DNA virus that replicates preferentially in
the liver. Liver-enriched nuclear receptors (NRs) play a major role in the HBV
life cycle, operating as essential transcription factors for viral gene
expression. Notably, these NRs are also key players in metabolic processes that
occur in the liver, serving as central transcription factors for key enzymes of
gluconeogenesis, fatty acid beta-oxidation, and ketogenesis. However, the
association between these metabolic events and HBV gene expression is poorly
understood. Here we show that peroxisome proliferator-activated receptor-gamma
coactivator 1alpha (PGC-1alpha), a major metabolic regulator and a coactivator of
key gluconeogenic genes, robustly coactivates HBV transcription. We further
demonstrate that the liver-enriched NR hepatocyte nuclear factor 4alpha that
binds HBV plays an important role in this process. Physiologically, we show that
a short-term fast that turns on the gluconeogenic program robustly induces HBV
gene expression in vivo. This induction is completely reversible by refeeding and
depends on PGC-1alpha. We conclude that HBV is tightly regulated by changes in
the body's nutritional state through the metabolic regulator PGC-1alpha. Our data
provide evidence for nutrition signaling to control viral gene expression and
life cycle and thus ascribe to metabolism an important role in virus-host
interaction.
PMID- 17043230
TI - Emergence of a bacterial clone with enhanced virulence by acquisition of a phage
encoding a secreted phospholipase A2.
AB - The molecular basis of pathogen clone emergence is relatively poorly understood.
Acquisition of a bacteriophage encoding a previously unknown secreted
phospholipase A(2) (designated SlaA) has been implicated in the rapid emergence
in the mid-1980s of a new hypervirulent clone of serotype M3 group A
Streptococcus. Although several lines of circumstantial evidence suggest that
SlaA is a virulence factor, this issue has not been addressed experimentally. We
found that an isogenic DeltaslaA mutant strain was significantly impaired in
ability to adhere to and kill human epithelial cells compared with the wild-type
parental strain. The mutant strain was less virulent for mice than the wild-type
strain, and immunization with purified SlaA significantly protected mice from
invasive disease. Importantly, the mutant strain was significantly attenuated for
colonization in a monkey model of pharyngitis. We conclude that transductional
acquisition of the ability of a GAS strain to produce SlaA enhanced the spread
and virulence of the serotype M3 precursor strain. Hence, these studies
identified a crucial molecular event underlying the evolution, rapid emergence,
and widespread dissemination of unusually severe human infections caused by a
distinct bacterial clone.
PMID- 17043231
TI - The genomic landscape of histone modifications in human T cells.
AB - To understand the molecular basis that supports the dynamic gene expression
programs unique to T cells, we investigated the genomic landscape of activating
histone modifications, including histone H3 K9/K14 diacetylation (H3K9acK14ac),
H3 K4 trimethylation (H3K4me3), and the repressive histone modification H3 K27
trimethylation (H3K27me3) in primary human T cells. We show that H3K9acK14ac and
H3K4me3 are associated with active genes required for T cell function and
development, whereas H3K27me3 is associated with silent genes that are involved
in development in other cell types. Unexpectedly, we find that 3,330 gene
promoters are associated with all of these histone modifications. The gene
expression levels are correlated with both the absolute and relative levels of
the activating H3K4me3 and the repressive H3K27me3 modifications. Our data reveal
that rapidly inducible genes are associated with the H3 acetylation and H3K4me3
modifications, suggesting they assume a chromatin structure poised for
activation. In addition, we identified a subpopulation of chromatin regions that
are associated with high levels of H3K4me3 and H3K27me3 but low levels of
H3K9acK14ac. Therefore, these regions have a distinctive chromatin modification
pattern and thus may represent a distinct class of chromatin domains.
PMID- 17043232
TI - Hereditary family signature of facial expression.
AB - Although facial expressions of emotion are universal, individual differences
create a facial expression "signature" for each person; but, is there a unique
family facial expression signature? Only a few family studies on the heredity of
facial expressions have been performed, none of which compared the gestalt of
movements in various emotional states; they compared only a few movements in one
or two emotional states. No studies, to our knowledge, have compared movements of
congenitally blind subjects with their relatives to our knowledge. Using two
types of analyses, we show a correlation between movements of congenitally blind
subjects with those of their relatives in think-concentrate, sadness, anger,
disgust, joy, and surprise and provide evidence for a unique family facial
expression signature. In the analysis "in-out family test," a particular movement
was compared each time across subjects. Results show that the frequency of
occurrence of a movement of a congenitally blind subject in his family is
significantly higher than that outside of his family in think-concentrate,
sadness, and anger. In the analysis "the classification test," in which
congenitally blind subjects were classified to their families according to the
gestalt of movements, results show 80% correct classification over the entire
interview and 75% in anger. Analysis of the movements' frequencies in anger
revealed a correlation between the movements' frequencies of congenitally blind
individuals and those of their relatives. This study anticipates discovering
genes that influence facial expressions, understanding their evolutionary
significance, and elucidating repair mechanisms for syndromes lacking facial
expression, such as autism.
PMID- 17043234
TI - Late Archean rise of aerobic microbial ecosystems.
AB - We report the (13)C content of preserved organic carbon for a 150 million-year
section of late Archean shallow and deepwater sediments of the Hamersley Province
in Western Australia. We find a (13)C enrichment of approximately 10 per thousand
in organic carbon of post-2.7-billion-year-old shallow-water carbonate rocks
relative to deepwater sediments. The shallow-water organic-carbon (13)C content
has a 29 per thousand range in values (-57 to -28 per thousand), and it contrasts
with the less variable but strongly (13)C-depleted (-40 to -45 per thousand)
organic carbon in deepwater sediments. The (13)C enrichment likely represents
microbial habitats not as strongly influenced by assimilation of methane or other
(13)C-depleted substrates. We propose that continued oxidation of shallow
settings favored the expansion of aerobic ecosystems and respiring organisms,
and, as a result, isotopic signatures of preserved organic carbon in shallow
settings approached that of photosynthetic biomass. Facies analysis of published
carbon-isotopic records indicates that the Hamersley shallow-water signal may be
representative of a late Archean global signature and that it preceded a similar,
but delayed, (13)C enrichment of deepwater deposits. The data suggest that a
global-scale expansion of oxygenated habitats accompanied the progression away
from anaerobic ecosystems toward respiring microbial communities fueled by
oxygenic photosynthesis before the oxygenation of the atmosphere after 2.45
billion years ago.
PMID- 17043233
TI - Vitamin K-dependent proteins in Ciona intestinalis, a basal chordate lacking a
blood coagulation cascade.
AB - We have isolated and sequenced several cDNAs derived from the sea squirt Ciona
intestinalis that encode vitamin K-dependent proteins. Four of these encode gamma
carboxyglutamic acid (Gla) domain-containing proteins, which we have named Ci
Gla1 through Ci-Gla4. Two additional cDNAs encode the apparent orthologs of gamma
glutamyl carboxylase and vitamin K epoxide reductase. Ci-Gla1 undergoes gamma
glutamyl carboxylation when expressed in CHO cells and is homologous to Gla-RTK,
a putative receptor tyrosine kinase previously identified in a related ascidian.
The remaining three Gla domain proteins are similar to proteins that participate
in fundamental developmental processes, complement regulation, and blood
coagulation. These proteins are generally expressed at low levels throughout
development and exhibit either relatively constant expression (Ci-Gla1, gamma
glutamyl carboxylase, and vitamin K epoxide reductase) or spatiotemporal
regulation (Ci-Gla2, -3, and -4). These results demonstrate the evolutionary
emergence of the vitamin K-dependent Gla domain before the divergence of
vertebrates and urochordates and suggest novel functions for Gla domain proteins
distinct from their roles in vertebrate hemostasis. In addition, these findings
highlight the usefulness of C. intestinalis as a model organism for investigating
vitamin K-dependent physiological phenomena, which may be conserved among the
chordate subphyla.
PMID- 17043235
TI - Global aggregation of newly translated proteins in an Escherichia coli strain
deficient of the chaperonin GroEL.
AB - In a newly isolated temperature-sensitive lethal Escherichia coli mutant
affecting the chaperonin GroEL, we observed wholesale aggregation of newly
translated proteins. After temperature shift, transcription, translation, and
growth slowed over two to three generations, accompanied by filamentation and
accretion (in approximately 2% of cells) of paracrystalline arrays containing
mutant chaperonin complex. A biochemically isolated inclusion body fraction
contained the collective of abundant proteins of the bacterial cytoplasm as
determined by SDS/PAGE and proteolysis/MS analyses. Pulse-chase experiments
revealed that newly made proteins, but not preexistent ones, were recruited to
this insoluble fraction. Although aggregation of "stringent" GroEL/GroES
dependent substrates may secondarily produce an "avalanche" of aggregation, the
observations raise the possibility, supported by in vitro refolding experiments,
that the widespread aggregation reflects that GroEL function supports the proper
folding of a majority of newly translated polypeptides, not just the limited
number indicated by interaction studies and in vitro experiments.
PMID- 17043236
TI - Distance measurements reveal a common topology of prokaryotic voltage-gated ion
channels in the lipid bilayer.
AB - Voltage-dependent ion channels are fundamental to the physiology of excitable
cells because they underlie the generation and propagation of the action
potential and excitation-contraction coupling. To understand how ion channels
work, it is important to determine their structures in different conformations in
a membrane environment. The validity of the crystal structure for the prokaryotic
K(+) channel, K(V)AP, has been questioned based on discrepancies with biophysical
data from functional eukaryotic channels, underlining the need for independent
structural data under native conditions. We investigated the structural
organization of two prokaryotic voltage-gated channels, NaChBac and K(V)AP, in
liposomes by using luminescence resonance energy transfer. We describe here a
transmembrane packing representation of the voltage sensor and pore domains of
the prokaryotic Na channel, NaChBac. We find that NaChBac and K(V)AP share a
common arrangement in which the structures of the Na and K selective pores and
voltage-sensor domains are conserved. The packing arrangement of the voltage
sensing region as determined by luminescence resonance energy transfer differs
significantly from that of the K(V)AP crystal structure, but resembles that of
the eukaryotic K(V)1.2 crystal structure. However, the voltage-sensor domain in
prokaryotic channels is closer to the pore domain than in the K(V)1.2 structure.
Our results indicate that prokaryotic and eukaryotic channels that share similar
functional properties have similar helix arrangements, with differences arising
likely from the later introduction of additional structural elements.
PMID- 17043237
TI - An inherent role of microtubule network in the action of nuclear receptor.
AB - Estrogen receptor alpha (ERalpha) functions as both a transcription factor and a
mediator of rapid estrogen signaling. Recent studies have shown a role for
ERalpha-interacting membranous and cytosolic proteins in ERalpha action, but our
understanding of the role of the microtubule network in the modulation of ERalpha
signaling remains unclear. Here we found that endogenous ERalpha associates with
microtubules through the microtubule-binding protein hematopoietic PBX
interaction protein (HPIP). Biochemical and RNA-interference studies demonstrated
that HPIP influences ERalpha-dependent rapid estrogen signaling by acting as a
scaffold protein and recruits Src kinase and the p85 subunit of
phosphatidylinositol 3-kinase to a complex with ERalpha, which in turn stimulates
AKT and MAPK. We also found that ERalpha interacts with beta-tubulin through
HPIP. Destabilization of microtubules activated ERalpha signaling, whereas
stabilization of microtubules repressed ERalpha transcriptional activity in a
HPIP-dependent manner. These findings revealed a role for HPIP-microtubule
complex in regulating 17beta-estradiol-ERalpha responses in mammalian cells and
discovered an inherent role of microtubules in the action of nuclear receptor.
PMID- 17043238
TI - Wild-type microglia extend survival in PU.1 knockout mice with familial
amyotrophic lateral sclerosis.
AB - The most common inherited form of amyotrophic lateral sclerosis (ALS), a
neurodegenerative disease affecting adult motoneurons, is caused by dominant
mutations in the ubiquitously expressed Cu(2+)/Zn(2+) superoxide dismutase
(SOD1). Recent studies suggest that glia may contribute to motoneuron injury in
animal models of familial ALS. To determine whether the expression of mutant SOD1
(mSOD1(G93A)) in CNS microglia contributes to motoneuron injury, PU.1(-/-) mice
that are unable to develop myeloid and lymphoid cells received bone marrow
transplants resulting in donor-derived microglia. Donor-derived microglia from
mice overexpressing mSOD1(G93A), an animal model of familial ALS, transplanted
into PU.1(-/-) mice could not induce weakness, motoneuron injury, or an ALS-like
disease. To determine whether expression of mSOD1(G93A) in motoneurons and
astroglia, as well as microglia, was required to produce motoneuron disease,
PU.1(-/-) mice were bred with mSOD1(G93A) mice. In mSOD1(G93A)/PU.1(-/-) mice,
wild-type donor-derived microglia slowed motoneuron loss and prolonged disease
duration and survival when compared with mice receiving mSOD1(G93A) expressing
cells or mSOD1(G93A) mice. In vitro studies confirmed that wild-type microglia
were less neurotoxic than similarly cultured mSOD1(G93A) microglia. Compared with
wild-type microglia, mSOD1(G93A) microglia produced and released more superoxide
and nitrite+nitrate, and induced more neuronal death. These data demonstrate that
the expression of mSOD1(G93A) results in activated and neurotoxic microglia, and
suggests that the lack of mSOD1(G93A) expression in microglia may contribute to
motoneuron protection. This study confirms the importance of microglia as a
double-edged sword, and focuses on the importance of targeting microglia to
minimize cytotoxicity and maximize neuroprotection in neurodegenerative diseases.
PMID- 17043239
TI - Human DNA polymerase kappa forms nonproductive complexes with matched primer
termini but not with mismatched primer termini.
AB - Human DNA polymerase kappa (pol kappa) is a member of the Y family of DNA
polymerases that function in translesion synthesis. It synthesizes DNA with
moderate fidelity and does not efficiently incorporate nucleotides opposite DNA
lesions. Pol kappa has the unusual ability to efficiently extend from mismatched
primer termini, and it extends readily from nucleotides inserted by other DNA
polymerases opposite a variety of DNA lesions. All of this has suggested that pol
kappa functions during the extension step of translesion synthesis. Here, we have
carried out pre-steady-state kinetic studies of pol kappa using DNA with matched
and mismatched primer termini. Interestingly, we find that mismatches present
only a modest kinetic barrier to nucleotide incorporation by pol kappa. Moreover,
and quite surprisingly, active-site titrations revealed that the concentration of
active pol kappa is very low with matched DNA, and from DNA trapping experiments
we determined that this was due to the formation of nonproductive protein.DNA
complexes. In marked contrast, we found that the concentration of active pol
kappa was six-fold greater with mismatched DNA than with matched DNA. Thus, pol
kappa forms nonproductive complexes with matched but not with mismatched DNA.
From these observations, we conclude that pol kappa has evolved to specifically
function on DNA substrates with aberrant primer-terminal base pairs, such as the
ones it would encounter during the extension step of translesion synthesis.
PMID- 17043240
TI - Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the
complex network of hemostasis.
AB - This article demonstrates that a simple chemical model system, built by using a
modular approach, may be used to predict the spatiotemporal dynamics of
initiation of blood clotting in the complex network of hemostasis. Microfluidics
was used to create in vitro environments that expose both the complex network and
the model system to surfaces patterned with patches presenting clotting stimuli.
Both systems displayed a threshold response, with clotting initiating only on
isolated patches larger than a threshold size. The magnitude of the threshold
patch size for both systems was described by the Damkohler number, measuring
competition of reaction and diffusion. Reaction produces activators at the patch,
and diffusion removes activators from the patch. The chemical model made
additional predictions that were validated experimentally with human blood
plasma. These experiments show that blood can be exposed to significant amounts
of clot-inducing stimuli, such as tissue factor, without initiating clotting.
Overall, these results demonstrate that such chemical model systems, implemented
with microfluidics, may be used to predict spatiotemporal dynamics of complex
biochemical networks.
PMID- 17043241
TI - Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin
dependent kinase 1.
AB - Androgen receptors (ARs) are phosphorylated at multiple sites in response to
ligand binding, but the kinases mediating AR phosphorylation and the importance
of these kinases in AR function have not been established. Here we show that
cyclin-dependent kinase 1 (Cdk1) mediates AR phosphorylation at Ser-81 and
increases AR protein expression, and that Cdk1 inhibitors decrease AR Ser-81
phosphorylation, protein expression, and transcriptional activity in prostate
cancer (PCa) cells. The decline in AR protein expression mediated by the Cdk
inhibitor roscovitine was prevented by proteosome inhibitors, indicating that
Cdk1 stabilizes AR protein, although roscovitine also decreased AR message
levels. Analysis of an S81A AR mutant demonstrated that this site is not required
for transcriptional activity or Cdk1-mediated AR stabilization in transfected
cells. The AR is active and seems to be stabilized by low levels of androgen in
"androgen-independent" PCas that relapse subsequent to androgen-deprivation
therapy. Significantly, the expression of cyclin B and Cdk1 was increased in
these tumors, and treatment with roscovitine abrogated responses to low levels of
androgen in the androgen-independent C4-2 PCa cell line. Taken together, these
findings identify Cdk1 as a Ser-81 kinase and indicate that Cdk1 stabilizes AR
protein by phosphorylation at a site(s) distinct from Ser-81. Moreover, these
results indicate that increased Cdk1 activity is a mechanism for increasing AR
expression and stability in response to low androgen levels in androgen
independent PCas, and that Cdk1 antagonists may enhance responses to androgen
deprivation therapy.
PMID- 17043242
TI - Microsporidian mitosomes retain elements of the general mitochondrial targeting
system.
AB - Microsporidia are intracellular parasites that infect a variety of animals,
including humans. As highly specialized parasites, they are characterized by a
number of unusual adaptations, many of which are manifested as extreme reduction
at the molecular, biochemical, and cellular levels. One interesting aspect of
reduction is the mitochondrion. Microsporidia were long considered to be
amitochondriate, but recently a tiny mitochondrion-derived organelle called the
mitosome was detected. The molecular function of this organelle remains poorly
understood. The mitosome has no genome, so it must import all its proteins from
the cytosol. In other fungi, the mitochondrial protein import machinery consists
of a network series of heterooligomeric translocases and peptidases, but in
microsporidia, only a few subunits of some of these complexes have been
identified to date. Here, we look at targeting sequences of the microsporidian
mitosomal import system and show that mitosomes do in some cases still use N
terminal and internal targeting sequences that are recognizable by import systems
of mitochondria in yeast. Furthermore, we have examined the function of the inner
membrane peptidase processing enzyme and demonstrate that mitosomal substrates of
this enzyme are processed to mature proteins in one species with a simplified
processing complex, Antonospora locustae. However, in Encephalitozoon cuniculi,
the processing complex is lost altogether, and the preprotein substrate functions
with the targeting leader still attached. This report provides direct evidence
for presequencing processing in mitosomes and also shows how a complex molecular
system has continued to degenerate throughout the evolution of microsporidia.
PMID- 17043244
TI - Isolation, characterization, and genetic complementation of a cellular mutant
resistant to retroviral infection.
AB - By using a genetic screen, we have isolated a mammalian cell line that is
resistant to infection by retroviruses that are derived from the murine leukemia
virus, human immunodeficiency virus type 1, and feline immunodeficiency virus. We
demonstrate that the cell line is genetically recessive for the resistance, and
hence it is lacking a factor enabling infection by retroviruses. The block to
infection is early in the life cycle, at the poorly understood uncoating stage.
We implicate the proteasome at uncoating by completely rescuing the resistant
phenotype with the proteasomal inhibitor MG-132. We further report on the
complementation cloning of a gene (MRI, modulator of retrovirus infection) that
can also act to reverse the inhibition of infection in the mutant cell line.
These data implicate a role for the proteasome during uncoating, and they suggest
that MRI is a regulator of this activity. Finally, we reconcile our findings and
other published data to suggest a model for the involvement of the proteasome in
the early phase of the retroviral life cycle.
PMID- 17043243
TI - Galectin-1 is essential in tumor angiogenesis and is a target for
antiangiogenesis therapy.
AB - We describe that galectin-1 (gal-1) is a receptor for the angiogenesis inhibitor
anginex, and that the protein is crucial for tumor angiogenesis. gal-1 is
overexpressed in endothelial cells of different human tumors. Expression
knockdown in cultured endothelial cells inhibits cell proliferation and
migration. The importance of gal-1 in angiogenesis is illustrated in the
zebrafish model, where expression knockdown results in impaired vascular guidance
and growth of dysfunctional vessels. The role of gal-1 in tumor angiogenesis is
demonstrated in gal-1-null mice, in which tumor growth is markedly impaired
because of insufficient tumor angiogenesis. Furthermore, tumor growth in gal-1
null mice no longer responds to antiangiogenesis treatment by anginex. Thus, gal
1 regulates tumor angiogenesis and is a target for angiostatic cancer therapy.
PMID- 17043245
TI - A role for adrenomedullin as a pain-related peptide in the rat.
AB - Adrenomedullin (AM) belongs to the calcitonin gene-related peptide (CGRP) family
and is a well known potent vasodilator. We show here that AM is a powerful pain
inducing neuropeptide. AM-like immunoreactivity is widely distributed in both
CGRP-containing and lectin IB4-binding nociceptors in dorsal root ganglion and
axon terminals in the superficial dorsal horn of the rat spinal cord. Specific
binding sites for the radioligand, [(125)I]AM13-52 as well as immunoreactivity
for receptor markers such as the calcitonin receptor-like receptor and three
receptor-activity-modifying proteins are localized in the superficial dorsal
horn, demonstrating the existence of AM/CGRP receptors in this region.
Intrathecal injection of rat AM1-50, dose- and time-dependently, induced long
lasting heat hyperalgesia and increased the phosphorylation of Akt and GSK3beta
in the dorsal horn. Pre- and posttreatments with the AM receptor antagonist AM22
52 and PI3 kinase inhibitors (LY294002 and Wortmannin) significantly blocked or
reversed AM-induced heat hyperalgesia. Pre- and posttreatments with AM22-52 and
Wortmannin also significantly blocked or reversed intraplantar capsaicin-induced
heat hyperalgesia. Taken together, our results demonstrate that AM acts as a pain
inducing peptide in the dorsal horn. By activating specific receptors (likely
AM2) and the PI3K/Akt/GSK3beta signaling pathway, AM could play a significant
role in long-lasting heat hypersensitivity and inflammatory heat hyperalgesia.
PMID- 17043246
TI - Contrary prostaglandins: the opposing roles of PGD2 and its metabolites in
leukocyte function.
AB - Traditionally, PGD(2) has been considered to be a pro-inflammatory mediator,
acting via classical PG receptors, such as the PGD(2) receptor (DP). PGD(2) is
degraded rapidly in vitro and in vivo to a variety of metabolites, the majority
of which were thought, until recently, to be physiologically inactive. Several
"inactive" metabolites, particularly 15d-PGJ(2), have been shown to have wide
ranging effects on leukocytes and other cell types, however, and a potentially
important anti-inflammatory role for PGD(2) has now been recognized, and the
complexity of PGD(2) signaling is beginning to be elucidated. PGD(2) and its
metabolites are biologically active over a broad concentration range, and,
intriquingly, it appears that there are marked concentration-dependent variations
in the consequences of signaling by these eicosanoids, which have the potential
to exert pro- and anti-inflammatory effects. For example, the actions of PGD(2)
can influence multiple stages in the life of the mature eosinophil, from causing
its release from the bone marrow to inducing its recruitment and activation and,
ultimately, regulating its apoptosis. This review is concerned with the diverse
responses induced in leukocytes by PGD(2) and its metabolites and the signaling
mechanisms which are thought to be responsible for them.
PMID- 17043247
TI - Incidence and survival rates for young blacks with nasopharyngeal carcinoma in
the United States.
AB - OBJECTIVES: To compare the incidence rates of nasopharyngeal carcinoma (NPC)
among US black, white, and Asian/Pacific Islander (Asian) populations, with a
focus on those diagnosed before age 20 years and between ages 20 and 29 years.
Our secondary objective was to determine differences in survival rates between US
blacks, whites, and Asians with NPC who were younger than 30 years. DESIGN: Data
from the National Cancer Institute Surveillance, Epidemiology, and End Results
(SEER) tumor registry system were used to determine incidence and survival rates
for cases of NPC diagnosed in the specified age groups between 1973 and 2002.
PATIENTS: Blacks, whites, and Asians younger than 30 years with NPC. MAIN OUTCOME
MEASURES: Incidence rates and 2- and 5-year survival rates. RESULTS: From 1973 to
2002, incidence rates per 1 million persons, adjusted to the 2000 standard
population, for blacks, whites, and Asians younger than 20 years with NPC were
1.61 (n=43), 0.61 (n=99), and 0.95 (n=18), respectively. The incidence rate ratio
of blacks to Asians younger than 20 years was 1.69 (95% confidence interval [CI],
0.96-3.12) (P=.07), while the rate ratio for blacks to whites was 2.66 (95% CI,
1.82-3.85) (P<.001). From ages 20 to 29 years, rates increased slightly in blacks
(1.87) and whites (0.96), while increasing dramatically in Asians (7.18). Two-
and 5-year relative survival rates in blacks younger than 30 years were 84% and
64%, respectively, with little variation between races in this age group.
CONCLUSIONS: Blacks younger than 20 years have increased incidence rates of NPC
relative to whites and may be the only group having a higher NPC incidence rate
than Asians. Two- and 5-year survival rates of blacks, whites, and Asians younger
than 30 years with NPC are similar.
PMID- 17043248
TI - Association between development of hypothyroidism and improved survival in
patients with head and neck cancer.
AB - OBJECTIVE: To determine if the development of hypothyroidism has an effect on the
outcome of advanced-stage head and neck squamous cell carcinoma. DESIGN:
Retrospective database analysis. SETTING: Tertiary care center. PATIENTS: The
study population comprised 155 patients with advanced-stage head and neck
squamous cell carcinoma. INTERVENTIONS: Patients underwent radiation therapy
alone or in combination with chemotherapy and surgery when indicated. MAIN
OUTCOME MEASURES: Kaplan-Meier analysis was used to assess survival, not
adjusting for timing of the detection of hypothyroidism. The following 2 analyses
were then performed to adjust for the timing of detection: (1) hypothyroidism was
assessed as a time-varying covariate in a Cox proportional hazards model and (2)
a landmark analysis was conducted at 9, 12, 15, 18, 21, and 24 months using the
Kaplan-Meier method. RESULTS: Of the 155 patients, 59 developed hypothyroidism,
defined as a thyrotropin level greater than 5.5 mIU/L (institutional value). An
unadjusted Kaplan-Meier analysis indicated that patients who develop
hypothyroidism have significantly better survival than patients who do not
(P<.001, log-rank test). After adjusting for the timing of hypothyroidism, a Cox
proportional hazards analysis indicated that survival was better, but not
statistically significant, for patients who developed hypothyroidism (hazard
ratio, 0.62; P=.12); results from a landmark analysis supported this finding (P
values ranged from .11 to .19). CONCLUSIONS: Development of hypothyroidism may be
associated with improved survival and increased recurrence-free survival. Larger,
prospective studies appear warranted to test the beneficial effect of
hypothyroidism.
PMID- 17043249
TI - Importance of routine evaluation of the thyroid gland prior to open partial
laryngectomy.
AB - OBJECTIVES: To determine the incidence and presentation of synchronous thyroid
lesions in a patient population undergoing open partial laryngectomy (OPL), and
to determine whether routine preoperative evaluation of the thyroid gland prior
to OPL is useful to identify synchronous thyroid lesions in order to reduce the
need for reoperation in this complex patient population. DESIGN: Retrospective
medical chart review. SETTING: Academic institution. PATIENTS: Sixty-seven
consecutive patients with laryngeal tumors who had undergone OPL from 1996 to
2005. INTERVENTIONS: Charts of 67 consecutive patients with laryngeal tumors who
underwent OPL in 1996 to 2005 have been reviewed for synchronous thyroid lesions.
For all patients, reports of (1) complete preoperative examination findings, (2)
inpatient course, (3) postoperative follow-up, and (4) postoperative final
histopathologic findings were reviewed. For patients with synchronous thyroid
lesions, reports of (1) thyroid evaluation and imaging and (2) preoperative (fine
needle aspiration), (3) intraoperative (frozen section), and (4) postoperative
(final) histopathologic results for the thyroid lesions were reviewed. MAIN
OUTCOME MEASURES: Incidence of synchronous thyroid lesions and laryngeal cancer
in patients undergoing OPL. RESULTS: Eight (11.9%) of 67 (95% confidence
interval, 5.3%-22.2%) patients with laryngeal tumors who underwent OPL had
evidence of synchronous thyroid lesions. All 8 patients had squamous cell
carcinoma of the larynx and underwent either supracricoid or supraglottic
laryngectomy. In these 8 patients, synchronous thyroid lesions were incidentally
detected. Four patients had papillary thyroid carcinoma, 1 had squamous
metaplasia, and 3 had follicular thyroid tissue that was negative for malignancy
on final pathologic examination. In 2 patients, the thyroid lesions were detected
preoperatively (prior to OPL); in another 2 patients, thyroid masses were
detected intraoperatively; and in 4 patients, the thyroid disease was identified
postoperatively on histopathologic examination of excised cervical lymph nodes.
In 2 patients, thyroidectomy was performed as a second operation after the OPL,
and 1 of them had transient vocal fold paralysis for 2 months. Thyroid
ultrasonography was performed in 4 patients. In 3 patients, the ultrasonography
was performed after the OPL final pathologic findings indicated the presence of
metastatic thyroid disease in cervical lymph nodes. Ultrasonography revealed
intrathyroidal lesions in all 3 patients. CONCLUSIONS: Patients with laryngeal
tumors who will be undergoing OPL might have occult synchronous thyroid lesions.
Thyroid surgery in patients with previous OPL may have an increased potential for
complication owing to postsurgical changes in the central neck region. Routine
preoperative evaluation of the thyroid gland, especially with ultrasonography, to
screen for occult synchronous thyroid lesions is recommended for all patients
with laryngeal tumors who will be undergoing OPL. Eradication of any thyroid
cancer detected preoperatively by fine-needle aspiration should be performed at
the same time as OPL. Pros and cons of total thyroidectomy for indeterminate
thyroid nodules should be discussed with this patient population.
PMID- 17043250
TI - The association between elevated EphB4 expression, smoking status, and advanced
stage disease in patients with head and neck squamous cell carcinoma.
AB - OBJECTIVE: To examine the expression of EphB4 in tumor tissue, surrounding normal
tissue, and metastatic lymph node in patients with head and neck squamous cell
carcinoma (HNSCC) and to evaluate its association with disease stage and smoking.
DESIGN: A retrospective study. SETTING: University of Southern California
University Hospital, University of Southern California and Los Angeles County
Medical Center, and Department of Otolaryngology-Head and Neck Surgery,
University of Southern California, Los Angeles. PATIENTS: Forty-eight patients
with different stages of HNSCC (I-IV) were enrolled into this study. Staging was
based on the staging system of the American Joint Committee on Cancer. MAIN
OUTCOME MEASURES: EphB4 expression in tumor tissue, surrounding normal tissue,
and metastatic lymph node was evaluated by immunohistochemical analysis, Western
blot, and real-time polymerase chain reaction. EphB4 expression was then compared
between patients based on disease stage and smoking status. RESULTS: EphB4
expression was detected in all tumor specimens and metastatic lymph nodes of
patients with HNSCC, but expression levels were higher in the metastatic lymph
nodes. There was a statistically significantly higher mean EphB4 protein
expression and EphB4 gene amplification in patients with advanced disease (stage
III or IV) vs patients with initial disease (stage I or II) and in smokers vs
nonsmokers. CONCLUSIONS: Overexpression of EphB4 is associated with advanced
stages of HNSCC as well as with patients who smoke. These data are the first to
demonstrate the association of EphB4 with advanced stages of disease and smoking
in HNSCC and hence provide a strong rationale for targeting EphB4 for HNSCC
therapies.
PMID- 17043251
TI - Lymphatic metastases to level IIb in hypopharyngeal squamous cell carcinoma.
AB - OBJECTIVES: To evaluate the prevalence of level IIb lymph node (LN) metastasis
and to identify potential clinical risk factors when level IIb metastatic
diseases are present in patients with clinically node-negative (N0) and node
positive (N+) necks with hypopharyngeal squamous cell carcinoma (HPSCC). This
will provide a basis for determining whether this region can be excluded in
elective or therapeutic neck dissection in patients with HPSCC. DESIGN:
Prospective analysis of a case series. SETTING: University hospital. PATIENTS:
Fifty patients with HPSCC who underwent surgical treatment for a primary lesion
and simultaneous neck dissection from January 1998 to February 2004. MAIN OUTCOME
MEASURES: The incidences and clinical risk factors for level IIb LN metastasis
and regional recurrence according to the presence or absence of pathologic LN
involvement in level IIb. RESULTS: A total of 93 neck dissections were analyzed
in this study. Of these dissections, 59 (63%) were elective and 34 (37%) were
therapeutic. Three percent (2 of 59) of all N0 necks and 32% (11 of 34) of all N+
necks had level IIb LN metastases. Level IIb nodal metastases were significantly
more prevalent in N+ necks (P=.007) than in N0 necks and in the presence of other
positive LNs (P=.01) than in the absence of other positive LNs. Of the 35
patients with pathologic LNs, the regional recurrence rate was significantly
higher in cases with positive level IIb LNs (33% [4 of 12]) than without (4% [1
of 23]; P=.04). CONCLUSIONS: Level IIb LN pads may be preserved during elective
neck dissection in the treatment of patients with clinically N0 necks with HPSCC.
This area should be removed during therapeutic neck dissection in the treatment
of clinically N+ necks.
PMID- 17043252
TI - Cricohyoidoepiglottopexy vs near-total laryngectomy with epiglottic
reconstruction in the treatment of early glottic carcinoma.
AB - OBJECTIVE: To compare functional and oncological outcomes of
cricohyoidoepiglottopexy (CHEP) and near-total laryngectomy with epiglottic
reconstruction (NTLER) techniques in early glottic carcinoma. DESIGN: Case
series, clinical study. SETTING: Two tertiary care referral centers. PATIENTS:
Seventeen patients with T1b glottic squamous cell carcinoma were treated with
CHEP and 21 were treated with NTLER. MAIN OUTCOME MEASURES: Fundamental
frequency, maximum phonation time, maximum phonation intensity, Voice Handicap
Index, and GRBAS (grade, roughness, breathiness, asthenia, and strain) scale were
used to evaluate voice. Nasogastric tube removal times and late postoperative
aspiration scales were used to evaluate swallowing ability. RESULTS: Fundamental
frequency (P=.78), maximum phonation time (P=.44), and maximum phonation
intensity (P=.94) measurements were not significantly different in the 2 groups.
There was also no significant difference in mean Voice Handicap Index score
(P=.62), mean decannulation time (P=.25), time to nasogastric tube removal
(P=.12), or clinical grades of late postoperative aspiration (P=.87) between the
2 groups. The mean Voice Handicap Index score was 55.58 in the CHEP group and
52.78 in the NTLER group. According to the GBRAS scale, overall voice quality was
moderately altered in both groups. All patients were successfully decannulated.
In the CHEP and NTLER groups, the mean decannulation times were 27 and 20 days,
respectively, and the nasogastric tubes were removed after an average of 23 and
17 days. The overall (Kaplan-Meier) survival rate was 94% in the patients who
underwent CHEP and 90% in the patients who underwent NTLER (P=.76). The disease
free survival rates were 100% and 76% in the CHEP and NTLER groups, respectively
(P=.07). CONCLUSIONS: Functional and oncological results appear to be similar
with both treatment methods. If open surgery is planned, the choice between these
procedures mainly depends on the experience and preference of the surgeon.
PMID- 17043253
TI - Randomized controlled trial of harmonic scalpel use during thyroidectomy.
AB - OBJECTIVE: To compare operative factors, postoperative outcomes, and surgical
complications of thyroidectomy when using the harmonic scalpel (HS) vs
conventional hemostasis (CH). DESIGN: Single-blind, randomized controlled trial.
SETTING: Department of Surgery, S. Chiara Hospital, University of Pisa, Pisa,
Italy. PATIENTS: One hundred patients undergoing thyroidectomy. MAIN OUTCOME
MEASURES: Postoperative pain, drainage volume, hypocalcemia, nerve injury, and
operative time. INTERVENTION: Patients underwent total thyroidectomy in which
either the HS or CH was used. RESULTS: We found no significant differences
between the HS and CH groups at baseline. Postoperative pain was reduced in the
HS group at 24 hours (mean visual analog scale score, 3.90 vs 5.30; P<.001) and
36 hours (2.27 vs 3.95; P<.001). Drainage volume was significantly lower in the
HS group (40.1 mL vs 75.4 mL; P<.001). Transient hypocalcemia was significantly
lower in the HS group (5 patients [10%] vs 16 [32%]; P=.01). No patients
experienced nerve injury or permanent hypocalcemia. Mean operative times were
shorter in the HS group (40.0 vs 46.7 minutes, P<.001). CONCLUSIONS: Use of the
HS may reduce postoperative pain, drainage volume, and transient hypocalcemia in
patients undergoing thyroidectomy. Shorter operative times and improved outcomes
might justify the cost of the HS compared with that of CH.
PMID- 17043254
TI - In vivo optical coherence tomography of the human oral cavity and oropharynx.
AB - Optical coherence tomography (OCT) is an evolving imaging modality that combines
interferometry with low-coherence light to produce high-resolution tissue
imaging. Cross-sectional in vivo images were obtained using an OCT device
consisting of a Michelson interferometer, 1.3-microm broadband light source, and
a handheld fiberoptic imaging probe. Image pixel resolution approached 10 microm.
The mucosa of the oral cavity and oropharynx were examined in 41 patients during
operative endoscopy. Optical coherence tomographic imaging was combined with
endoscopic photography for gross and histologic image correlation. Optical
coherence tomographic images of the oral cavity and oropharynx provided
microanatomical information on the epithelium, basement membrane (BM), and
supporting lamina propria (LP) of the mucosa. Normal microstructures identified
in these tissues included an overlying keratin layer, papillae, ducts, glands,
and blood vessels. Regions of pathologic features studied included mature scar,
granulation tissue, mucous cysts, leukoplakia, and invasive cancer. Optical
coherence tomographic imaging showed distinct zones of normal, altered, and
ablated tissue microstructures for each pathologic process studied. Abnormal
findings were directly compared with regions of normal tissue or conventional
histopathologic features when tissue for analysis was available. This study
provides a composite series of in vivo OCT images of the oral cavity and
oropharynx in a variety of normal regions and pathologic states as well as
outline future applications of OCT technology.
PMID- 17043255
TI - Efficacy of sucralfate in the postoperative management of
uvulopalatopharyngoplasty: a double-blind, randomized, controlled study.
AB - OBJECTIVE: To evaluate the effectiveness of sucralfate in influencing throat
pain, otalgia, analgesic requirement, bleeding, mucosal recovery, and incidence
of postoperative bleeding in patients undergoing uvulopalatopharyngoplasty.
DESIGN: A prospective double-blind randomized study. SETTING: University
affiliated tertiary referral hospital. PARTICIPANTS: Eighty adult patients with
obstructive sleep apnea syndrome requiring uvulopalatopharyngoplasty were
recruited and randomly allocated into either a sucralfate treatment group or a
control group. INTERVENTIONS: All patients underwent uvulopalatopharyngoplasty.
Patients enrolled in the sucralfate group (n=40) were instructed to gargle the
sucralfate suspension and then to swallow. Patients enrolled in the control group
(n=40) were instructed to gargle placebo suspension at the same doses and
schedule. MAIN OUTCOME MEASURES: Postoperative throat pain, otalgia, amount of
analgesic required, degree of strength (defined as patients' general well-being
and return to regular daily activities), percentage of mucosal covering, and
postoperative bleeding. RESULTS: Throat pain and otalgia occurred significantly
less often in sucralfate group, with less analgesic requirement and with rapid
mucosal healing and early return to regular daily activities. There was no
significant difference in episodes of postoperative bleeding between the 2 groups
(P=.37). CONCLUSIONS: Although sucralfate therapy may not provide complete
analgesia after uvulopalatopharyngoplasty, it may reduce the amount of analgesic
required, thus preventing dose-related adverse effects from the analgesic agent.
It can also significantly reduce the total number of days needed to return to
normal daily activities (P=.41).
PMID- 17043256
TI - Bacterial colonization of airway stents: a promoter of granulation tissue
formation following laryngotracheal reconstruction.
AB - OBJECTIVE: To investigate whether airway granulation, a common occurrence during
laryngotracheal reconstructive surgery and a common cause of delays in definitive
treatment and treatment failure, is associated with a microbial etiology. DESIGN:
Prospective case-control study. SETTING: Tertiary referral airway reconstruction
unit. PATIENTS: Patients who had an airway stent as part of their treatment for
laryngotracheal stenosis. INTERVENTIONS: All airway stents were sent for
microbiological analysis. Information about patient demographics, lesion
characteristics, and presence of airway granulation tissue at different times
during treatment were obtained and correlated against the microbiological
findings from airway stents. MAIN OUTCOME MEASURES: A chi2 test was used to
correlate airway colonization with specific pathogens and occurrence of airway
granulation. Logistic regression analysis was used to identify independent
microbiological predictors of airway granulation. RESULTS: Thirty-one airway
stents were removed from 26 patients. The mean (SD) age at presentation was 42
(18) years, and postintubation tracheal stenosis was the most common etiology.
There were highly significant associations between stent colonization with
Staphylococcus aureus and Pseudomonas aeruginosa and the occurrence of airway
granulation (P<.02), and these microorganisms were independently associated with
the risk of developing airway granulation. Furthermore, S aureus was associated
with persistence of airway granulation on average 4 months following removal of
the stent. CONCLUSIONS: Airway granulation seems to be associated not with
polymicrobial airway colonization but with infection with specific pathogenic
microorganisms. All patients undergoing laryngotracheoplasty should receive
antibiotic prophylaxis to cover these microorganisms, and the development and use
of antibiotic-impregnated airway stents should be explored.
PMID- 17043257
TI - Risk factors for serious complication after uvulopalatopharyngoplasty.
AB - OBJECTIVE: To test the hypothesis that comorbidity, performance of concurrent
sleep apnea procedures in addition to uvulopalatopharyngoplasty, body mass index,
apnea-hypopnea index, and lowest oxygen saturation are risk factors for serious
perioperative complications after uvulopalatopharyngoplasty. DESIGN: Prospective
cohort and nested case-control studies. SETTING: United States Veterans Affairs
medical centers. PATIENTS: A prospective cohort of 3130 consecutive adult
inpatients who underwent uvulopalatopharyngoplasty from 1991 to 2001 was
retrospectively analyzed from the Veterans Affairs National Surgical Quality
Improvement Program database to determine the relationship between perioperative
complications and both concurrent procedures and medical comorbidity. A nested
case-control analysis was conducted on 43 cases with complications and 212
controls without complications from the cohort. Controls were matched on age,
sex, year of operation, and concurrent surgery; this case-control analysis
enabled the study of body mass index, apnea-hypopnea index, and lowest oxygen
saturation, which were not available in the cohort database. Multivariate
logistic regression measured associations between risk factors and complications,
adjusting or controlling for age, sex, race, smoking status, year of
uvulopalatopharyngoplasty, and presence of any concurrent procedure. MAIN OUTCOME
MEASURE: Sixteen specific serious perioperative complications, including 30-day
mortality. RESULTS: The cohort included 3130 veterans (97% were men aged 50+/-11
[mean+/-SD] years). In the cohort study, comorbidity was associated with serious
complication: the adjusted risk ratio was 1.96 (95% confidence interval, 1.16
3.18) for each increase in American Society of Anesthesiologists class.
Concurrent nonnasal procedures increased the risk of complication compared with
no concurrent procedures (adjusted risk ratio, 4.94; 95% confidence interval,
2.34-10.4). In the case-control analyses, the apnea-hypopnea index, body mass
index, and medical comorbidity were each associated with serious complication
after adjustment for confounding variables, but this study had insufficient power
to determine if these risk factors were independent of each other. Concurrent
retrolingual procedures demonstrated an independent association with complication
after adjustment for confounders. The lowest oxygen saturation was not associated
with serious complication. CONCLUSIONS: Apnea-hypopnea index, body mass index,
and medical comorbidity were each associated with serious complication; however,
the low complication rate precluded demonstration of associations independent of
each other. Concurrent retrolingual procedures were also associated with serious
complication, but the cumulative risk of separate retrolingual procedures is
unknown.
PMID- 17043258
TI - Bacteriology of chronic sinusitis and acute exacerbation of chronic sinusitis.
AB - OBJECTIVE: To establish the microbiological characteristics of acute exacerbation
of chronic sinusitis (AECS). SETTING: Academic medical center. PATIENTS: Thirty
two patients with chronic sinusitis and 30 patients with AECS. MAIN OUTCOME
MEASURE: The aerobic and anaerobic microbiology of maxillary AECS and chronic
maxillary sinusitis. RESULTS: A total of 81 isolates (33 aerobic and 48
anaerobic) were recovered from the 32 cases (2.5 per specimen) with chronic
sinusitis. Aerobes alone were recovered in 8 specimens (25%), anaerobes only were
isolated in 11 (34%), and mixed aerobes and anaerobes were recovered in 13 (41%).
The predominant aerobic and facultative bacteria were Enterobacteriaceae and
Staphylococcus aureus. The predominant anaerobic bacteria were Peptostreptococcus
subspecies, Fusobacterium subspecies, anaerobic gram-negative bacilli, and
Propionibacterium acnes. Twenty-one beta-lactamase-producing bacteria were
recovered from 17 specimens (53%). A total of 89 isolates (40 aerobic and
facultatives, and 49 anaerobic) were recovered from the 30 patients (3.0 per
specimen) with AECS. Aerobes were recovered in 8 instances (27%), anaerobes only
in 11 (37%), and mixed aerobes and anaerobes were recovered in 11 (37%). The
predominant aerobes were Streptococcus pneumoniae, Enterobacteriaceae, and S
aureus. The predominant anaerobes were Peptostreptococcus subspecies,
Fusobacterium subspecies, anaerobic gram-negative bacilli, and P acnes. Thirty
six beta-lactamase-producing bacteria were recovered from 28 specimens (53%).
CONCLUSIONS: This study demonstrates that the organisms isolated from patients
with AECS were predominantly anaerobic and were similar to those generally
recovered in patients with chronic sinusitis. However, aerobic bacteria that are
usually found in acute infections (eg, S pneumoniae, Haemophilus influenzae, and
Moraxella catarrhalis) can also emerge in some of the episodes of AECS.
PMID- 17043259
TI - Effect of genetic background on the response to bacterial sinusitis in mice.
AB - OBJECTIVE: To study the importance of ongoing allergen exposure and TH1/TH2
genetic background in augmented bacterial and inflammatory responses in allergic
and infected mice. DESIGN: BALB/c and C57BL/6 mice were made allergic to
ovalbumin. After 1 day of intranasal allergen exposure, they were inoculated
intranasally with Streptococcus pneumoniae. The numbers of bacteria and
inflammatory cells in the sinuses were determined, and nasal responsiveness to
histamine was assessed. RESULTS: Infected BALB/c and C57BL/6 mice that received
ongoing ovalbumin challenge following intraperitoneal sensitization showed
significantly greater bacterial load and phagocyte level compared with the
infected-only mice. Differences were diminished after the allergen challenge was
stopped. Allergic and infected C57BL/6 mice showed fewer bacteria and phagocytes
compared with the allergic and infected BALB/c mice. Surprisingly, in contrast to
the nonallergenic C57BL/6 mice, the infected BALB/c mice showed a larger number
of bacteria 28 days after infection. CONCLUSIONS: Ongoing allergic reaction
augments bacterial load in both BALB/c and C57BL/6 mice and induces nasal
hyperreactivity to histamine. Allergic and infected C57BL/6 mice show less
allergic inflammation and bacterial load compared with allergic and infected
BALB/c mice. Stopping allergen exposure reduces the response. Infected BALB/c
mice, which favor a TH2 response, were less able to clear infection than C57BL/6
mice, which favor a TH1 response. Inflammation and bacterial load are affected by
genetic background of mice and ongoing allergen stimulation.
PMID- 17043260
TI - Eustachian tube function in patients with eosinophilic otitis media associated
with bronchial asthma evaluated by sonotubometry.
AB - OBJECTIVE: To determine eustachian tube function in patients with asthma and with
or without eosinophilic otitis media (EOM), a new middle ear disease entity with
a highly viscous middle ear effusion containing many eosinophils and usually
associated with bronchial asthma. One of the most important causes of otitis
media (OM) is eustachian tube dysfunction. DESIGN: Retrospective case review.
SETTING: A referral center. PATIENTS: Twenty patients with EOM and patients with
asthma but without OM. MAIN OUTCOME MEASURES: We studied eustachian tube function
using sonotubometry and a questionnaire. Sonotubometry was also performed on 13
control patients with chronic otitis media (COM) and 7 normal controls. RESULTS:
The tubal opening duration was significantly longer in patients with EOM than in
patients with asthma but without OM, controls with COM, and normal controls,
indicating the presence of patulous eustachian tubes in patients with EOM.
Responses to the questionnaire also supported the presence of patulous eustachian
tubes in the patients with EOM. CONCLUSIONS: The presence of a patulous
eustachian tube may be a major cause of EOM in patients with bronchial asthma. In
patients with asthma who have a helper T-cell 2-dominant predisposition, a
patulous eustachian tube easily allows the entry of antigenic materials into the
middle ear, causing eosinophil-dominant inflammation.
PMID- 17043261
TI - Predictors of chronic suppurative otitis media in children.
AB - OBJECTIVE: To determine which factors predict development of chronic suppurative
otitis media (CSOM) in children. DESIGN: Case-control study, with univariate and
multivariate logistic regression analysis applied to determine which factors
independently predict CSOM. SUBJECTS: Prognostic factors for CSOM were identified
in (1) 100 children with CSOM and 161 controls aged 1 to 12 years and (2) 83
children who developed CSOM in the presence of a tympanostomy tube and 136
children with tympanostomy tubes who did not develop CSOM. RESULTS: Independent
predictors for CSOM were previous tympanostomy tube insertion (odds ratio [OR],
121.4 [95% confidence interval {CI}, 38.9-379.3]); having had more than 3 upper
respiratory tract infections in the past 6 months (OR, 12.2 [95% CI, 3.5-42.3]);
having parents with a low education level (OR, 14.1 [95% CI, 2.9-68.6]); and
having older siblings (OR, 4.4 [95% CI, 1.6-12.6]). Independent predictors for
CSOM after tympanostomy tube insertion were having experienced more than 3
episodes of otitis media in the past year (OR, 4.9 [95% CI, 2.2-11.0]; attending
day care (OR, 3.6 [95% CI, 1.7-7.8]); and having older siblings (OR, 2.6 [95% CI,
1.2-5.5]). CONCLUSIONS: Treatment with tympanostomy tubes is the most important
prognostic factor for CSOM in children. In children who are being treated with
tympanostomy tubes for persistent middle ear effusion, the most important
prognostic factor for CSOM is a history of recurrent episodes of acute otitis
media. This information should be taken into consideration and discussed with
parents when considering insertion of tympanostomy tubes in children.
PMID- 17043262
TI - Piriform sinus tracts in children.
AB - OBJECTIVES: To describe the various presentations and management of piriform
sinus tracts in children and to provide a treatment algorithm. DESIGN: Case
series. SETTING: Pediatric otolaryngology service in a tertiary care setting.
PATIENTS: Eight pediatric patients diagnosed as having a piriform sinus tract
between 1999 and 2005. INTERVENTIONS: Patients were treated with surgical
excision, endoscopic cauterization, or observation. MAIN OUTCOME MEASURE:
Recurrence of neck infection. RESULTS: Three different modes of presentation were
identified. Four patients presented primarily with an intrathyroidal abscess; 2
presented with recurrent deep neck infections requiring repeated drainage; and 2
presented with symptoms unrelated to the tract. Barium swallows identified the
tracts in 5 of 8 patients, and telescopic hypopharyngoscopy identified the tracts
in all 8 patients. Five patients were treated with complete excision of their
tracts; 1 was treated with cauterization of the internal opening; and 2 were
observed for symptoms related to the tracts. All 8 patients are currently
asymptomatic. CONCLUSIONS: Piriform sinus tracts are rare. Most patients with
tracts present with recurrent deep neck infections. Telescopic hypopharyngoscopy
is the diagnostic modality of choice. Endoscopic cauterization is recommended as
the initial therapy in symptomatic patients, with complete excision reserved for
recurrences. Observation is appropriate for asymptomatic patients.
PMID- 17043263
TI - Adenotonsillectomy for obstructive sleep apnea in obese children: effects on
respiratory parameters and clinical outcome.
AB - OBJECTIVE: To assess the efficacy of adenotonsillar surgery on respiratory sleep
parameters and avoiding continuous positive airway pressure (CPAP) treatment in
morbidly obese children with obstructive sleep apnea syndrome (OSAS). DESIGN:
Retrospective. SETTING: Tertiary referral institution. PATIENTS: Children aged 2
to 18 years, with a body mass index (BMI) at or higher than the 95th percentile
(adjusted for age and sex), undergoing adenotonsillar surgery for OSAS.
INTERVENTIONS: Adenotonsillectomy. MAIN OUTCOME MEASURES: Preoperative and
postoperative respiratory disturbance index, oxygen saturation nadir, overall
severity of OSAS (mild, moderate, or severe) and candidacy for CPAP treatment
were assessed and compared. Variables such as age, severity of disease,
adenotonsillar size, and BMI z scores were compared between responders and
nonresponders to surgical treatment. RESULTS: A total of 19 patients with full
preoperative and postoperative data for evaluation were identified. The median
(SD) age was 78 months (53.3 months). The median (SD) BMI z score was 2.84
(0.94). Eighteen patients (95%) had OSAS preoperatively to warrant CPAP
treatment. Surgery reduced the overall median (SD) respiratory disturbance index
from 20.7 (24.5) to 7.3 (14.9) (P<.001) and improved the median (SD) oxygen
saturation nadir from 77.5% (16.3%) to 88.5 (13.1%) (P<.01). A total of 7
patients (37%) were cured by surgery. Ten patients (53%) had postoperative
disease of sufficient severity to require CPAP. Surgery obviated the need for
further treatment in only 8 (44%) of the 18 patients with preoperative disease
warranting CPAP. No differences were identified between responders and
nonresponders to surgical treatment. CONCLUSIONS: Adenotonsillar surgery improves
sleep respiratory parameters in morbidly obese children with OSAS. Most patients
have residual OSAS requiring further treatment.
PMID- 17043264
TI - An update in thinking about nonorganic voice disorders.
AB - OBJECTIVE: To describe and evaluate psychosocial factors in nonorganic voice
disorders (NVDs). Nonorganic voice disorders are presumed to be the result of
increased muscular tension that is caused to varying extents by vocal misuse and
emotional stress. It is therefore necessary to include both of these in the
diagnosis and treatment of patients with voice disorders. DESIGN: Clinical
survey. SETTING: Academic tertiary referral center. PATIENTS: To evaluate
psychosocial factors in NVDs, a sample of 74 patients with NVDs was examined
psychologically using the Giessen Test and Picture Frustration Test. The results
were compared with a control group of 19 patients with an organic dysphonia
(vocal cord paralysis). MAIN OUTCOME MEASURES: Six scales of the Giessen Test
(social response, dominance, control, underlying mood, permeability, and social
potency), 3 reaction types of the Picture Frustration Test (obstacle dominance,
ego defense, and need persistence), and 3 aggression categories of the Picture
Frustration Test (extrapunitivity, intropunitivity, and impunitivity). RESULTS:
The most striking significant difference between the 2 groups was that in
conflict situations, patients with NVDs sought a quick solution or expected other
people to provide one, which prevented them from understanding the underlying
causes of the conflict. CONCLUSIONS: Only if the psychosocial aspects are taken
into account can patients with NVD be offered a therapy that treats the causes of
the voice disorder. It must be decided individually whether and when a voice
training approach or a more psychological-psychotherapeutical approach is
preferable.
PMID- 17043265
TI - Central auditory development in children with bilateral cochlear implants.
AB - OBJECTIVE: To examine the time course of maturation of P1 latencies in infant
sequential and simultaneous bilateral cochlear implant recipients. DESIGN:
Retrospective case series. SETTING: Pediatric collaborative cochlear implant
program. PATIENTS: Four children who received bilateral cochlear implants prior
to age 2 years. INTERVENTION: Cortical auditory evoked potential was completed to
determine the latency of the P1 response in 4 children with bilateral cochlear
implants. MAIN OUTCOME MEASURES: Longitudinal development of the latency of the
P1 cortical auditory evoked potential in children who received bilateral cochlear
implants prior to age 2 years. RESULTS: In 2 patients who received sequential
bilateral implants, P1 latencies recorded from the first implanted ear were
within normal limits after 3 to 6 months of implant use. By comparison, P1
latencies from the second implanted ear reached normal limits as early as 1 month
after implant use. In 2 patients who received simultaneous bilateral implants, P1
latencies from both ears were also within normal limits in a very short time
frame (ie, by 1 month poststimulation). CONCLUSIONS: Our data suggest a high
degree of plasticity of the central auditory pathways after early bilateral
implantation. We find that P1 latencies provide a clinically useful biomarker of
central auditory system development in children after cochlear implantation.
PMID- 17043266
TI - Stored human septal chondrocyte viability analyzed by confocal microscopy.
AB - OBJECTIVES: To analyze the effects of prolonged storage time, at warm and cold
temperatures, on the viability of human nasal septal chondrocytes and to
understand the implications for tissue engineering of septal cartilage. DESIGN:
Basic science. SUBJECTS: Septal cartilage was obtained from 10 patients and
placed in bacteriostatic isotonic sodium chloride solution. Four specimens were
kept at 23 degrees C, and 4 were kept at 4 degrees C. The viability of the
chondrocytes within the cartilage was assessed using confocal laser scanning
microscopy every 5 days. The 2 other specimens were assessed for viability on the
day of harvest. RESULTS: Viability on the day of harvest was 96%, implying
minimal cell death from surgical trauma. After 1 week, cell survival in all
specimens was essentially unchanged from the day of harvest. At 23 degrees C, the
majority (54%) of cells were alive after 20 days. At 4 degrees C, 70% of cells
survived 1 month and 38% were alive at 2 months. Qualitatively, chondrocytes died
in a topographically uniform distribution in warm specimens, whereas cold
specimens displayed a more irregular pattern of cell death. CONCLUSION: Septal
chondrocytes remain viable for prolonged periods when stored in simple
bacteriostatic isotonic sodium chloride solution, and such survival is enhanced
by cold storage.
PMID- 17043267
TI - Auricular seroma: a new concept, and diagnosis and management of 16 cases.
PMID- 17043268
TI - Dural arteriovenous fistula presenting as subjective pulsatile tinnitus.
PMID- 17043269
TI - Radiology quiz case 1. Diagnosis: supernumerary intranasal tooth.
PMID- 17043270
TI - Radiology quiz case 2. Diagnosis: basal cell adenoma (BCA) of the minor salivary
gland involving the left parapharyngeal space.
PMID- 17043271
TI - Pathology quiz case 1. Diagnosis: carcinoid tumor of the middle ear.
PMID- 17043272
TI - Pathology quiz case 2. Diagnosis: malakoplakia of the left tongue base.
PMID- 17043273
TI - When fine-needle aspiration biopsy cannot exclude papillary thyroid cancer: a
therapeutic dilemma.
AB - HYPOTHESIS: Clinical or cytologic factors predictive of malignancy can be
identified and incorporated into a treatment algorithm for patients with a fine
needle aspiration biopsy (FNAB) specimen interpreted as "suspicious for"
papillary thyroid cancer (PTC). DESIGN: Retrospective review of a prospectively
maintained database. SETTING: University-affiliated tertiary care hospital.
PATIENTS: Seven hundred thirty-eight patients with nodular thyroid disease
evaluated between 1990 and 2004. INTERVENTIONS: Patients with an FNAB specimen
suspicious for PTC were identified. The frequency of carcinoma was determined.
Clinical features were reviewed. The FNAB specimens suspicious for PTC were
examined in a blinded fashion to determine if specific cytologic features were
important in distinguishing benign vs malignant disease. MAIN OUTCOME MEASURES:
The presence of specific clinical and cytologic features was correlated with the
incidence of carcinoma. A secondary outcome measure was to determine the value of
frozen section examination in establishing the extent of thyroidectomy. RESULTS:
Forty-five patients (7%) had an FNAB specimen suspicious for PTC; 18 (40%) of
these patients had carcinoma. Prominent nuclear inclusions and/or grooves,
papillary formations, and the absence of colloid were features associated with
PTC (P<.05). No clinical features reliably identified malignant disease. Frozen
section examination results altered treatment in 15 (56%) of 27 patients.
CONCLUSIONS: An FNAB specimen suspicious for PTC is associated with a 40%
incidence of carcinoma. Extensive nuclear inclusions and/or grooves, papillary
formations, and the absence of colloid are predictive of carcinoma. Rare
intranuclear inclusions and/or grooves alone in an otherwise benign-appearing
specimen are uniformly associated with benign disease. Frozen section examination
is of value in determining the extent of thyroidectomy.
PMID- 17043274
TI - Cancer antigens 19-9 and 125 in the differential diagnosis of pancreatic mass
lesions.
AB - HYPOTHESIS: Accurate differentiation between inflammatory and neoplastic tumors
of the pancreas remains a diagnostic dilemma for surgeons. The aim of the study
was to assess the utility of 2 neoplastic markers, cancer antigen (CA) 19-9 and
CA 125, in the differential diagnosis of pancreatic tumors. DESIGN: The patients
were assigned to a malignant or benign group based on cytological and
histological evaluation of pancreatic lesion samples. The serum from each patient
was tested for CA 19-9 and CA 125. SETTING AND PATIENTS: One hundred ten patients
with heterogeneous pancreatic lesions (inflammatory and malignant tumors) treated
at a surgical department of a university hospital were analyzed. INTERVENTIONS:
Samples for cytological and histological evaluation were taken during
ultrasonography-guided fine-needle aspiration biopsy or open surgery. MAIN
OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive
values of each test in the differential diagnosis of pancreatic tumors were
determined. RESULTS: The sensitivity, specificity, positive predictive value, and
negative predictive value of the CA 19-9 test were 80.8%, 89.1%, 93.7%, and
89.2%, respectively. The sensitivity, specificity, positive predictive value, and
negative predictive value of the CA 125 test were 60.8%, 83.3%, 88.2%, and 50.8%,
respectively. The sensitivity and specificity of a combined evaluation of both CA
19-9 and CA 125 tests were 87.8% and 77.8%, respectively. CONCLUSIONS: Taking
into account the high but still limited sensitivity and specificity of the CA 19
9 and CA 125 tests, their results in the differential diagnosis of pancreatic
tumors should be interpreted consistently and in reference to imaging techniques
such as ultrasonography and computed tomography.
PMID- 17043275
TI - Part-time training in general surgery: results of a web-based survey.
AB - HYPOTHESIS: The recent increase in female medical school enrollment and emphasis
on lifestyle considerations for both men and women pose challenges for residency
recruitment and retention. This study was designed to assess interest in part
time surgical training. We hypothesized that more women than men would be
interested in this option. DESIGN: A Web-based survey soliciting demographic
information and opinions about training priorities was distributed to medical
students, surgery residents, fellows, and trained surgeons. Respondents were
asked to express on a 5-point Likert scale interest in (and deterrents to)
substituting 1 or more years of standard residency with a shorter workweek (< 80
hours but > 40 hours) in exchange for a proportionately overall longer length of
training. SETTING: The survey was located on the American College of Surgeons Web
site. PARTICIPANTS: Medical students (482), surgical residents (789), fellows
(179), and fully trained surgeons (2858) affiliated with at least 1 of 4 major
surgical societies. RESULTS: There were 4308 respondents (76% male). Of physician
respondents, 9.1% had taken time out of residency for nonresearch reasons. Thirty
six percent of female and 24% of male students agreed to increased interest in
surgical careers if part-time training were an option (P = .005). Twenty-five
percent of female and 13% of male residents (P<.001) expressed interest in this
option. Prolonged training was cited as the primary deterrent. CONCLUSIONS:
Eleven percent to 36% of total male and female respondents expressed interest in
pursuing part-time training. Significantly more women than men favored a part
time option.
PMID- 17043276
TI - Treatment of elderly breast cancer patients in a community hospital setting.
AB - HYPOTHESIS: Elderly breast cancer patients are underdiagnosed and undertreated in
a community hospital setting. DESIGN: Retrospective study of tumor registry
patients. SETTING: Community hospital. PATIENTS: A total of 354 breast cancer
patients aged 70 years or older diagnosed between 1992 and 2002 were identified
from the tumor registry. The data for 3 prospectively chosen age subgroups (aged
70-74, 75-79, and > or =80 years) were subsequently analyzed. MAIN OUTCOME
MEASURES: Data were collected regarding the method of detection of cancer, tumor
characteristics and staging, type of treatment, and patient comorbidities.
Comparisons between age subgroups were made using a likelihood ratio chi2 test.
RESULTS: Forty-six percent of all patients presented with palpable breast cancer.
Mammography was frequently used as an adjunct to the physical examination but was
helpful in detecting occult disease in only 54% of all patients and 38% of
patients older than 80 years. Although more than 70% of patients were considered
stage I or II, complete pathologic staging was only performed in 64% of patients.
Approximately 50% of patients were treated with breast-conservation surgery;
however, adjuvant radiation therapy was omitted in 55% of these patients.
Additionally, only 29% of patients with positive lymph nodes received
chemotherapy, and 67% patients who were estrogen receptor-positive received
adjuvant hormonal therapy. CONCLUSIONS: Older breast cancer patients are more
likely to be diagnosed and staged clinically. Mammography is underused as a
screening modality. While breast-conservation surgery was performed in about half
of the patients, adjuvant radiation, chemotherapy, and hormonal therapies were
frequently excluded.
PMID- 17043277
TI - The therapeutic efficacy of edaravone in extensively burned rats.
AB - BACKGROUND: Extensive burn injury leads to production of free radicals subsequent
to massive fluid resuscitation, which in turn increases the risk of acute lung
injury. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical
scavenger, is clinically effective in improving the prognosis after cerebral
infarction. However, the effect of edaravone against extensive burn injury has
not been tested. Objected To evaluate whether edaravone can reduce free radical
precursors in a 30% burn model in rats. DESIGN: Prospective, randomized
controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male
Wistar rats weighing 200 to 220 g. MAIN OUTCOME MEASURES: All rats (n = 10) were
given a 30% full-thickness burn according to the Walker and Mason method.
Immediately after the burn, edaravone was injected into the rats (n = 5)
intraperitoneally at a dose of 9 mg/kg. One hour after burn injury, blood and
tissue samples were collected to analyze free radical changes of serum and tissue
malondialdehyde (MDA) and xanthine oxidase (XOD) and lung white blood cells.
RESULTS: Statistical significance was found between nontreatment and edaravone
treatment relative to serum MDA (mean +/- SD, 2.50 +/- 0.54 vs 1.74 +/- 0.29
nmol/mL), serum XOD (mean +/- SD, 5.04 +/- 1.67 vs 2.26 +/- 0.83 U/L), tissue MDA
(mean +/- SD, 1268.7 +/- 289.9 vs 569.1 +/- 135.9 nmol/mg protein), tissue XOD
(mean +/- SD, 256.3 +/- 58.1 vs 50.96 +/- 19.60 mU/g tissue), lung white blood
cells (mean +/- SD, 3088 +/- 1144 vs 1542 +/- 575 mU/g tissue), and lung XOD
(mean +/- SD, 428.3 +/- 210.5 vs 81.8 +/- 36.0 nmol/mg protein). CONCLUSIONS:
Edaravone treatment induces significant reduction of free radical precursors and
their metabolites compared with controls in burn rats. This suggests that
edaravone could be helpful in the clinical treatment of large burns.
PMID- 17043278
TI - Metastatic neuroendocrine hepatic tumors: resection improves survival.
AB - BACKGROUND: The optimal treatment for hepatic metastases from neuroendocrine
tumors remains controversial because of the often indolent nature of these
tumors. We sought to determine the effect of 3 major treatment modalities
including medical therapy, hepatic artery embolization, and surgical resection,
ablation, or both in patients with liver-only neuroendocrine metastases, with the
hypothesis that surgical treatment is associated with improvement in survival.
DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: Patients
with metastatic liver-only neuroendocrine tumors were identified from hospital
records. INTERVENTIONS: Patients were subdivided into those receiving medical
therapy, hepatic artery embolization, or surgical management. MAIN OUTCOME
MEASURES: Effect of treatment on survival and palliation of symptoms was
analyzed. RESULTS: From January 1996 through May 2004, 48 patients with liver
only neuroendocrine metastases were identified (median follow-up, 20 months),
including 36 carcinoid and 12 islet cell tumors. Seventeen patients were treated
conservatively, which consisted of octreotide (n = 7), observation (n = 6), or
systemic chemotherapy (n = 4). Hepatic artery embolization was performed in 18
patients. Thirteen patients underwent surgical therapy, including anatomical
liver resection (n = 6), ablation (n = 4), or combined resection and ablation (n
= 3). No difference was noted in the percentage of liver involved with tumor
between the 3 groups. An association of improved survival was noted in patients
treated surgically, with a 3-year survival of 83% for patients treated by
surgical resection, compared with 31% in patients treated with medical therapy or
embolization (P = .01). No difference in palliation of symptoms was noted among
the 3 treatment groups (P = .2). CONCLUSION: In patients with liver-only
neuroendocrine metastases, surgical therapy using resection, ablation, or both is
associated with improved survival.
PMID- 17043279
TI - Selection criteria for simultaneous resection in patients with synchronous liver
metastasis.
AB - HYPOTHESIS: While simultaneous resection has been shown to be safe and effective
in patients with synchronous metastasis, neoadjuvant chemotherapy followed by
hepatectomy has gradually gained acceptance for both initially nonresectable
metastasis and resectable metastasis. The boundary between these treatments is
becoming unclear. We hypothesized that factors associated with colorectal cancer
may play an important role in the prognosis of patients with synchronous
metastasis and may be useful for identifying patients who can be expected to have
adequate results following simultaneous resection. DESIGN: Outcome study.
SETTING: Tertiary referral center. PATIENTS: From January 1980 to December 2002,
187 patients underwent curative resection for synchronous liver metastasis from
colorectal cancer. One hundred forty-two patients received simultaneous
resection, 18 underwent staged resection, and 27 underwent delayed hepatic
resection. Twenty-one clinicopathological factors were analyzed, and long-term
prognosis was assessed. MAIN OUTCOME MEASURES: Prognostic factors and patient
survival. RESULTS: There was no in-hospital death. In a multivariate analysis,
the factors that significantly affected the prognosis of synchronous metastasis
were 4 or more lymph node metastases around the primary cancer (P<.001) and
multiple liver metastases (P = .003). In patients with 3 or fewer lymph node
metastases around the primary cancer, the 5-year survival rates of those with 1,
2 to 3, and 4 or more liver metastases were 63%, 33%, and 40%, respectively, but
these rates were 15%, 22%, and 0%, respectively, in patients with 4 or more lymph
node metastases around the primary cancer. CONCLUSIONS: The results support the
application of simultaneous resection in patients with 0 to 3 colorectal lymph
node metastases. However, in patients with 4 or more colorectal lymph node
metastases, biological selection by neoadjuvant chemotherapy may be more
suitable.
PMID- 17043280
TI - Surgical site infection following bowel surgery: a retrospective analysis of 1446
patients.
AB - HYPOTHESIS: We sought to determine whether the administration of preoperative
antibiotics, intraoperative transfusion of blood products, and intraoperative
hypothermia has any impact on the incidence of postoperative surgical site
infections (SSIs) in a heterogeneous patient population undergoing bowel surgery.
DESIGN: Retrospective analysis. SETTING: From September through December 2002,
data on 1472 patients undergoing bowel surgery at 31 academic medical centers in
the United States were collected. PATIENTS: Patients were included in the
analysis if they were older than 17 years of age and underwent any surgery
involving the small bowel, colon, or rectum. Main Outcome Measure Postoperative
SSI. Variables that might affect the risk for developing SSIs were analyzed using
multivariate logistic regression analysis. RESULTS: Perioperative transfusion (P
= .04; odds ratio, 1.64), and the presence of any infection at the time of
surgery (P = .05; odds ratio, 2.46) were independent risk factors for SSI.
Patients with a lower intraoperative temperature nadir had a lower risk for SSI
(P = .05; odds ratio, 1.33), although this difference is not clinically
significant (35.8 degrees C +/- 0.8 degrees C vs 36.0 degrees C +/- 0.9 degrees
C, P<.05). There was a trend toward statistical significance for wound class when
added to the multivariate model (P = .09; odds ratio, 1.41). The administration
of antibiotics within 120 minutes prior to incision or within 120 minutes prior
to and 120 minutes after incision had no effect on SSIs in this patient
population. CONCLUSIONS: This study validates perioperative transfusion as an
independent risk factor for SSI. The lack of effectiveness of perioperative
antibiotic prophylaxis is surprising because it is discordant with the previous
literature, and this finding needs further evaluation.
PMID- 17043281
TI - Ethical and regulatory challenges associated with the exception from informed
consent requirements for emergency research: from experimental design to
institutional review board approval.
AB - Clinical research studies conducted in emergency settings under the waiver of
consent provision outlined in federal regulations are uncommon, yet the
importance of such research that may result in potentially lifesaving
interventions is indisputable. Surgeons, as well as health care professionals in
other disciplines of medicine, should be aware of the multiple challenges facing
them if they contemplate conducting a research trial without the prospective
informed consent of enrolled subjects. The challenges associated with conducting
research studies using the exception from informed consent requirements for
emergency research are numerous, beginning with ensuring an appropriate study
design, understanding state and federal regulations that govern such emergency
research studies, and continuing through a complicated and sometimes arduous
institutional review board (IRB) process that is unique to these studies. This
article will describe the challenges encountered when implementing the exception
from informed consent requirements for emergency research and will provide
surgeon researchers with an understanding of the ethical controversies
surrounding such studies.
PMID- 17043282
TI - Methods and complications of anterior exposure of the thoracic and lumbar spine.
AB - OBJECTIVE: To review the methods and complications of exposing the anterior
aspects of the thoracic and lumbosacral spine. DATA SOURCES: PubMed (journals
database of the National Library of Medicine), text books, the University
HealthSystem Consortium Clinical Process Improvement Benchmarking Project, a
newspaper, and the US government Healthcare Cost and Utilization Project. STUDY
SELECTION: Descriptions of morbidity and mortality specifically related to
anterior spine exposure depicted in both case reports and clinical series were
used. DATA EXTRACTION: Mortality data from clinical series with more than 30
cases were tabulated. Morbidity incidences were described. DATA SYNTHESIS: The
frequency of anterior exposure of the spine for structural operations is steadily
increasing. Both thoracic and lumbosacral anterior spine operations are
associated with exposure-related complication rates of 10% to 50%. Pulmonary
complications are frequent after thoracic exposures. Chylothorax is the most
common of several rarer chest-exposure complications. Vascular complications,
particularly arterial thrombosis (<1% of cases) and venous bleeding (2%-15% of
cases), are the most frequent complications at the lumbar level. Other
lumbosacral exposure complications include ureteral and nerve (somatic and
sympathetic) injury. The mortality rate in anterior spine exposures is less than
1%. CONCLUSIONS: The exposure portions of anterior spine operations result in
numerous complications. There are fewer reported complications with endoscopic
exposures of the anterior spine than with open exposures, although endoscopic
exposures have been used for less complicated cases. In comparable cases, neither
exposure nor results of endoscopic operations have proven better than operations
done through minilaparotomy incisions. Perioperative cooperation between exposing
and spine surgeons is necessary to enhance results in anterior spine operations.
PMID- 17043283
TI - Groin hernia: anatomical and surgical history.
AB - The history of surgical repair of groin hernia is a lengthy record of assorted
techniques in search of a cure for an ailment that comes in many sizes and shapes
and that has plagued humanity for thousands of years. Although improvements are
still being sought and found, for several decades surgeons have had the means to
relieve most hernia sufferers. A remaining issue is whether the wide array of
surgical procedures can or should be whittled down to a few "standard" operations
that are safe, effective, and cost-efficient. The history of the anatomy of groin
hernia shows how much there was to learn and how much remains to be learned. It
also shows how important it is for the surgeon to know and understand both the
anatomy of the area and the formation of groin hernia.
PMID- 17043284
TI - Image of the month. Cecal gastrointestinal stromal tumor.
PMID- 17043285
TI - Image of the month. Mesenteric lipoma.
PMID- 17043286
TI - Associations of HLA-C alleles with multinodular goiters.
PMID- 17043287
TI - Wrong-site surgery.
PMID- 17043288
TI - Futility of positron emission tomography and other modalities in the initial
radiographic screening of patients with melanoma.
PMID- 17043289
TI - Camptocormia in Parkinson's disease: new insights.
PMID- 17043290
TI - Defining and quantifying coping strategies after stroke: a review.
AB - The coping strategies that people use after a stroke may influence recovery.
Coping measures are generally used to assess the mediating behaviour between a
stressor (ie, disease or condition) and the physical or psychological outcome of
an individual. This review evaluates measures that quantified coping strategies
in studies on psychological adaptation to stroke. The main aspects of the coping
measures reviewed were (a) conceptual basis; (b) coping domains assessed; (c)
coping strategies used after a stroke; and (d) psychometric properties of coping
measures used in studies assessing patients with stroke. Four databases (Medline,
CINAHL, PsychINFO and Cochrane Systematic Reviews) were searched to identify
studies that used a coping measure in stroke. 14 studies assessed coping
strategies in patients after stroke. Ten different coping measures were used, and
the studies reviewed had many limitations. Few studies provided definitions of
"coping" and the psychometric properties of the coping measures were under
reported. The need for future studies to more clearly define the coping process
and to present data on the reliability and validity of the measures used is
emphasised.
PMID- 17043291
TI - Essential tremor: predictors of disease progression in a clinical cohort.
AB - OBJECTIVES: To examine the utility of baseline factors to predict disease
progression among a clinical cohort of patients diagnosed with essential tremor.
MEASURES: Tremor Rating Scale (TRS). METHODS: A clinical series of 128
consecutive patients diagnosed with essential tremor was included for study. 45
(35%) patients had at least one follow-up exam (mean = 3.6 years). Baseline
predictive factors examined included age, age at onset of symptoms, disease
duration, sex, handedness, total tremor rating score, asymmetric tremor ratings,
location of initial tremor onset, use of drugs for movement disorders, ETOH
responsiveness of tremor, association of head or neck tremor, history of
depression, familial history of essential tremor, Parkinson's disease,
Alzheimer's disease and other movement disorders. RESULTS: On average, the TRS
total score increased by <1 point per year before the first visit to the clinic
and by about 2 points per year during the observed study period. The increase of
2 points per year during the observed study period represented an approximate 12%
annual change from the mean TRS total score at the first clinic visit.
Significant (p<0.05) predictive factors associated with increased tremor severity
at the initial clinic visit included older age, longer disease duration, use of
movement disorder drugs and the presence of voice tremor (r = 0.24, 0.27, 0.25,
0.19). The major factors associated with an increase in tremor severity from the
initial clinic visit to the last follow up included asymmetrical tremor ratings,
unilateral initial tremor onset and longer follow-up duration (r = 0.32, 0.31,
0.30). Multivariate regression analysis accounted for about 17-30% of the
variance in tremor ratings (p<0.05). CONCLUSION: Essential tremor is a slow,
progressive disease. The rate of disease progression and the factors associated
with disease progression may vary throughout the disease course.
PMID- 17043292
TI - Neurological picture. Intracranial calcifications and activating mutation of the
calcium-sensing receptor.
PMID- 17043293
TI - Neurological picture. Production of oil in a brain abscess caused by
Propionibacterium acnes.
PMID- 17043294
TI - Pontomedullary sulcus infarct: a variant of lateral medullary syndrome.
AB - With the advent of magnetic resonance imaging (MRI) technology, it is now
possible to identify and determine the precise location of medullary infarcts.
The lateral part of the medulla is most commonly affected by infarction.
Classifications of lateral medullary infarcts are usually based on anatomical
data, using rostrocaudal and dorsoventral axes to establish correlations with
clinical symptoms. Different subtypes of lateral medullary syndrome, depending on
location, shape and size of the infarct, have been described in the literature.
We report a rare case of a patient presenting with an unusual clinical picture in
relation to an infarct specifically located in the lateral part of the
pontomedullary sulcus.
PMID- 17043296
TI - Myotonic dystrophy: practical issues relating to assessment of strength.
AB - BACKGROUND: Myotonic dystrophy type 1 is a slowly progressive multisystem disease
in which skeletal muscle involvement is prominent. As novel physical and
pharmacological treatments become available, it is crucial to be able to measure
their efficacy accurately. METHODS: 158 consecutive patients with myotonic
dystrophy were assessed annually in a specialist muscle clinic. Strength was
measured using both the Medical Research Council (MRC) scale and a hand-held
dynamometer. Dynamometer readings were obtained from 108 normal subjects
(controls). RESULTS: The movements showing the greatest rate of change in
strength were ankle dorsiflexion and pinch grip. Both of these showed a decline
of only 0.06 points/year on the MRC scale. Using a hand-held dynamometer, a
change in strength of 1.18 kgN/year for women and 1.61 kgN/year for men was
detected. CONCLUSIONS: The MRC scale is unsuitable for detecting the small
changes in strength seen in a slowly progressive disease such as myotonic
dystrophy. Dynamometry provides a simple alternative that can give meaningful
data over the duration of a typical clinical trial.
PMID- 17043295
TI - Interleukin 10, monocytes and increased risk of early infection in ischaemic
stroke.
AB - BACKGROUND AND PURPOSE: The pathophysiology of stroke-associated infection (SAI)
is uncertain. The cytokine profile and peripheral white cell response were
assessed in patients with or without SAI. METHODS: The incidence of SAI was
assessed in 110 patients with ischaemic stroke allocated antibiotic prophylaxis
or placebo within 24 h of clinical onset. Peripheral white cell counts,
interleukin (IL)6, tumour necrosis factor (TNF)alpha and IL10 were measured in
plasma. RESULTS: 17 (15%) patients developed infection and showed time-dependent
increases of total white cell count, neutrophils, monocytes, lymphocytes, IL6 and
IL10, whereas TNFalpha and the TNFalpha/IL10 ratio decreased. In logistic
regression, IL10 (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.01 to
1.16), monocyte count (OR 1.42, 95% CI 1.08 to 1.87) and National Institute for
Health Stroke Survey score on admission (OR 1.17, 95% CI 1.05 to 1.31) were
independent predictors of systemic infection. CONCLUSIONS: SAI is associated with
stroke severity, excessive IL10-mediated response and an increased number of
circulating monocytes. These results support the finding that acute ischaemic
brain injury triggers a blood-borne anti-inflammatory response that decreases the
antimicrobial drive of the immune system.
PMID- 17043297
TI - Increased cerebrospinal fluid and serum levels of S100B in first-onset
schizophrenia are not related to a degenerative release of glial fibrillar acidic
protein, myelin basic protein and neurone-specific enolase from glia or neurones.
AB - OBJECTIVE: To assess levels of glial fibrillar acidic protein (GFAP), myelin
basic protein (MBP), neurone-specific enolase (NSE) and S100B in patients with
first-onset schizophrenia. METHOD: We investigated CSF and serum samples from 12
patients with first-onset schizophrenia and from 17 control subjects by ELISA
(GFAP, MBP) or immunoluminometric sandwich assays (NSE, S100B). RESULTS: Patients
with schizophrenia had significantly higher levels of S100B in CSF (p = 0.004;
2.73 (SD 0.80) v 1.92 (0.58) microg/l) and serum (p = 0.032; 0.09 (0.03) v 0.08
(0.02) microg/l) in comparison with those in the matched control group. No
diagnosis-dependent differences of protein concentration were seen for GFAP, MBP
and NSE. DISCUSSION: Our finding of increased levels of S100B in patients with
schizophrenia without an indication for significant glial (GFAP, MBP) or neuronal
(NSE) damage may be interpreted as indirect evidence for increased active
secretion of S100B during acute psychosis.
PMID- 17043299
TI - Sturge-Weber syndrome (encephalotrigeminal or leptomeningeal angiomatosis).
PMID- 17043298
TI - Changes in optic nerve head blood flow in children with cerebral malaria and
acute papilloedema.
AB - OBJECTIVE: To investigate capillary blood flow in the optic nerve head (ONH) of
children with cerebral malaria. METHODS: Malawian children with cerebral malaria
admitted to a paediatric research ward were examined by direct and indirect
ophthalmoscopy. ONH blood flow was measured using laser Doppler flowmetry (LDF)
in suitable patients. Mean blood volume and velocity were obtained from 30 to 60
s recordings from the temporal ONH and used to calculate blood flow. These were
compared with admission variables, funduscopic findings and disease outcomes.
RESULTS: 45 children with cerebral malaria had LDF recordings; 6 subsequently
died and 5 survivors had neurological sequelae. 12 (27%) had papilloedema. The
mean microvascular blood volume was higher in patients with papilloedema (3.28 v
2.54 arbitrary units, p = 0.002). The blood velocity correlated directly with
haematocrit (r = 0.46, p = 0.001) and inversely with blood glucose (r = -0.49, p
= 0.001). CONCLUSION: The increase in ONH microvascular blood volume in
papilloedema measured by LDF is consistent with current theories of pathogenesis
of papilloedema. LDF has potential as a tool to distinguish papilloedema from
pseudopapilloedematous disc swellings. The relationship between blood velocity
and haematocrit may relate to levels of sequestration in cerebral malaria.
PMID- 17043300
TI - Reinfection with Lyme borreliosis presenting as a painful polyradiculopathy:
Bannwarth's, Beevor's and Borrelia.
PMID- 17043301
TI - Pigmentary macular dystrophy in spinocerebellar ataxia type 1.
PMID- 17043302
TI - What's in a name--familial rectal pain syndrome becomes paroxysmal extreme pain
disorder.
PMID- 17043303
TI - Email triage for new neurological outpatient referrals: what the customers think.
PMID- 17043304
TI - Now dear, I have a headache! Immediate improvement of cluster headaches after
sexual activity.
PMID- 17043305
TI - Denoising feedback loops by thresholding--a new role for microRNAs.
PMID- 17043306
TI - Spineless provides a little backbone for dendritic morphogenesis.
PMID- 17043307
TI - Histone H3 Lys 4 methylation: caught in a bind?
PMID- 17043308
TI - Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter
determines the Xist transcription program.
AB - Initiation of X inactivation depends on the coordinated expression of the
sense/antisense pair Xist/Tsix. We show here that a precisely defined Xist
promoter region flanked by CTCF is maintained by Tsix in a heterochromatic-like
state in undifferentiated embryonic stem (ES) cells and shifts to a
pseudoeuchromatic structure upon Tsix truncation. We further demonstrate that the
epigenetic state of the Xist 5' region prior to differentiation predicts the
efficiency of transcriptional machinery recruitment to the Xist promoter during
differentiation. Our results provide mechanistic insights into the Tsix-mediated
epigenetic regulation of Xist resulting in Xist promoter activation and
initiation of X inactivation in differentiating ES cells.
PMID- 17043309
TI - Identification of Sin1 as an essential TORC2 component required for complex
formation and kinase activity.
AB - Target of rapamycin (TOR) is an evolutionally conserved protein kinase in
eukaryotes and a central cell growth controller. TOR exists in two distinct
complexes, termed TORC1 and TORC2. Mammalian TORC2 has recently been shown to
possess kinase activity toward the C-terminal hydrophobic site of Akt/PKB. Here,
we report that Sin1 is an essential component of TORC2 but not of TORC1, and
functions similarly to Rictor, the defining member of TORC2, in complex formation
and kinase activity. Knockdown of Sin1decreases Akt phosphorylation in both
Drosophila and mammalian cells and diminishes Akt function in vivo. It also
disrupts the interaction between Rictor and mTOR. Furthermore, Sin1 is required
for TORC2 kinase activity in vitro. Disruption of the Rictor gene in mice results
in embryonic lethality and ablates Akt phosphorylation. These data demonstrate
that Sin1 together with Rictor are key components of mTORC2 and play an essential
role in Akt phosphorylation and signaling.
PMID- 17043310
TI - Hedgehog-regulated localization of Vax2 controls eye development.
AB - Cell fates in the optic neuroepithelium are determined by the combinational
action of homeotic transcription factors. One of these is Vax2, a homeodomain
protein that ventralizes the vertebrate eye field by repressing transcription of
the Pax6 gene. We find that Vax2 shuttles between the nucleus and cytoplasm as a
function of time in eye development, and that this dynamic shuttling is an
essential feature of retinal differentiation. We show that subcellular
localization of Vax2 is controlled by phosphorylation of a single serine residue,
S170, downstream from its homeodomain, and that this modification results in the
exclusion of Vax2 from the nucleus. Phosphorylation of S170 is most probably
mediated by protein kinase A and is antagonized by the ventralizing morphogen
Sonic hedgehog. Expression of a nonphosphorylatable, constitutively nuclear Vax2
protein in the chick optic vesicle results in constitutive repression of Pax6,
and leads to the formation of an eyeless embryo. These results indicate that
regulated changes in Vax2 localization modify the developmental competence of the
optic neuroepithelium over time and thereby provide a mechanism for the
sequential staging of eye development.
PMID- 17043311
TI - Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and
suppresses an imprinting defect in the PWS/AS domain.
AB - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by deficiency
of imprinted gene expression from paternal or maternal chromosome 15q11-q13,
respectively. Genomic imprinting of the PWS/AS domain is regulated through a
bipartite cis-acting imprinting center (PWS-IC/AS-IC) within and upstream of the
SNRPN promoter. Here, we show that two Rb-binding protein-related genes,
Rbbp1/Arid4a and Rbbp1l1/Arid4b, are involved in the regulation of imprinting of
the IC. We recovered these two genes from gene trap mutagenesis selecting for
altered expression of an Snrpn-EGFP fusion gene strategy. RBBP1/ARID4A is an Rb
binding protein. RBBP1/ARID4A interacts with RBBP1L1/ARID4B and with the Snrpn
promoter, implying that both are part of a protein complex. To further elucidate
their roles on regulation of imprinting, we deleted the Rbbp1/Arid4a and
Rbbp1l1/Arid4b genes in mice. Combined homozygous deficiency for Rbbp1/Arid4a and
heterozygous deficiency for Rbbp1l1/Arid4b altered epigenetic modifications at
the PWS-IC with reduced trimethylation of histone H4K20 and H3K9 and reduced DNA
methylation, changing the maternal allele toward a more paternal epigenotype.
Importantly, mutations of Rbbp1/Arid4a, Rbbp1l1/Arid4b, or Rb suppressed an AS
imprinting defect caused by a mutation at the AS-IC. These data identify
Rbbp1/Arid4a and Rbbp1l1/Arid4b as new members of epigenetic complexes regulating
genomic imprinting at the PWS/AS domain.
PMID- 17043312
TI - Role of Brg1 and HDAC2 in GR trans-repression of the pituitary POMC gene and
misexpression in Cushing disease.
AB - Negative feedback regulation of the proopiomelanocortin (POMC) gene by the
glucocorticoid (Gc) receptor (GR) is a critical feature of the hypothalamo
pituitary-adrenal axis, and it is in part exerted by trans-repression between GR
and the orphan nuclear receptors related to NGFI-B. We now show that Brg1, the
ATPase subunit of the Swi/Snf complex, is essential for this trans-repression and
that Brg1 is required in vivo to stabilize interactions between GR and NGFI-B as
well as between GR and HDAC2. Whereas Brg1 is constitutively present at the POMC
promoter, recruitment of GR and HDAC2 is ligand-dependent and results in histone
H4 deacetylation of the POMC locus. In addition, GR-dependent repression inhibits
promoter clearance by RNA polymerase II. Thus, corecruitment of repressor and
activator at the promoter and chromatin modification jointly contribute to trans
repression initiated by direct interactions between GR and NGFI-B. Loss of Brg1
or HDAC2 should therefore produce Gc resistance, and we show that approximately
50% of Gc-resistant human and dog corticotroph adenomas, which are the hallmark
of Cushing disease, are deficient in nuclear expression of either protein. In
addition to providing a molecular basis for Gc resistance, these deficiencies may
also contribute to the tumorigenic process.
PMID- 17043313
TI - Inhibition of homologous recombination by a cohesin-associated clamp complex
recruited to the rDNA recombination enhancer.
AB - Silencing within the yeast ribosomal DNA (rDNA) repeats protects the integrity of
this highly repetitive array by inhibiting hyperrecombination and repressing
transcription from foreign promoters. Using affinity purification combined with
highly sensitive mixture mass spectrometry, we have analyzed the protein
interaction network involved in suppressing homologous recombination within the
rDNA locus. We show that the Net1 and Sir2 subunits of the RENT (regulator of
nucleolar silencing and telophase exit) silencing complex, and Fob1, which
recruits RENT to the nontranscribed spacer I (NTS1) region of rDNA, are
physically associated with Tof2. In addition to RENT components and Fob1, Tof2
copurified with a two-subunit complex composed of Lrs4 and Csm1. Tof2, Lrs4, and
Csm1 are recruited to the NTS1 region by Fob1 and are specifically required for
silencing at this rDNA region. Moreover, Lrs4 and Csm1 act synergistically with
Sir2 to suppress unequal crossover at the rDNA and are released from the
nucleolus during anaphase. Together with previous observations showing that Csm1
physically associates with cohesin, these findings suggest a possible model in
which RENT, Tof2, and Lrs4/Csm1 physically clamp rDNA to the cohesin ring,
thereby restricting the movement of rDNA sister chromatids relative to each other
to inhibit unequal exchange.
PMID- 17043314
TI - Canalization of auxin flow by Aux/IAA-ARF-dependent feedback regulation of PIN
polarity.
AB - Plant development is characterized by a profound ability to regenerate and form
tissues with new axes of polarity. An unsolved question concerns how the position
within a tissue and cues from neighboring cells are integrated to specify the
polarity of individual cells. The canalization hypothesis proposes a feedback
effect of the phytohormone auxin on the directionality of intercellular auxin
flow as a means to polarize tissues. Here we identify a cellular and molecular
mechanism for canalization. Local auxin application, wounding, or auxin
accumulation during de novo organ formation lead to rearrangements in the
subcellular polar localization of PIN auxin transport components. This auxin
effect on PIN polarity is cell-specific, does not depend on PIN transcription,
and involves the Aux/IAA-ARF (indole-3-acetic acid-auxin response factor)
signaling pathway. Our data suggest that auxin acts as polarizing cue, which
links individual cell polarity with tissue and organ polarity through control of
PIN polar targeting. This feedback regulation provides a conceptual framework for
polarization during multiple regenerative and patterning processes in plants.
PMID- 17043315
TI - Impact of intervention surveillance bias on analyses of child welfare report
outcomes.
AB - Two studies using data from child maltreatment intervention outcome evaluations
were conducted examining several aspects of surveillance bias, including directly
measuring rates of surveillance reporting, comparing characteristics of
surveillance versus nonsurveillance reports, examining differences across service
types and doses, and testing how ignoring versus removing surveillance reports in
the data affects survival analysis. The net effect of surveillance bias was small
in the studies examined. Home-visiting services were not biased more than center
based services, and bias was not greater among intervention compared to
prevention cases. Surveillance reports were equally as severe as nonsurveillance
reports, failing to support the hypothesis that surveillance serves as early
detection of less severe maltreatment. However, surveillance bias was far more
substantial during time periods when participants were actively engaged in
services. Therefore, the net impact of surveillance could vary with service
engagement rates and the relative duration of service engagement and postservice
follow-up times.
PMID- 17043316
TI - Completing substance abuse treatment in child welfare: the role of co-occurring
problems and primary drug of choice.
AB - A significant number of substance-abusing parents in the child welfare system do
not complete substance abuse treatments. Consequently, their children experience
longer stays in substitute care settings, and the risk of the termination of
parental rights is increased. This study identifies and determines the specific
factors that explain the completion of substance abuse treatment for substance
abusing caregivers in child welfare. The sample includes 871 caregivers enrolled
in the Illinois Alcohol and Other Drug Abuse waiver demonstration. Approximately
22% of these caregivers successfully completed all required levels of substance
abuse treatment. The multivariate models indicate that age, employment status,
and legal involvement were significantly associated with the likelihood of
completing substance abuse treatment. Heroin users were significantly less likely
to complete treatment as compared with alcohol, cocaine, and marijuana users. The
findings are discussed in terms of policy and practice implications for public
child welfare systems.
PMID- 17043317
TI - Prenatal cocaine exposure and child welfare outcomes.
AB - This study examines the relationship between prenatal cocaine exposure and child
welfare outcomes. Seventy-six infants positive for cocaine at birth were matched
to 76 negative infants. With prenatal care and maternal use of alcohol and
tobacco controlled, cocaine-exposed infants had significant decrements in birth
weight, length, head circumference, and depressed 5-min Apgar scores. This
confirmed the health risk of prenatal cocaine exposure for the sample. Three-year
follow-up data were obtained from the State Central Register and foster care
records. Adjusting for prior maternal involvement with child welfare services the
study groups did not differ in incidents of child maltreatment or foster care
placement. These findings suggest that prenatal cocaine exposure is not a marker
for abusive parenting. However, from the perspective of a cumulative risk model,
the identification of cocaine-exposed infants at birth can form the starting
point for the development of appropriate diagnostic and follow-up services for
mother and child.
PMID- 17043318
TI - This is my child: differences among foster parents in commitment to their young
children.
AB - In this study, the authors examined variables associated with foster mothers'
level of commitment to their young foster children, who ranged in age from 5
months to 5 years. Commitment was assessed using a semistructured interview known
as the "This Is My Baby" interview (TIMB; Bates & Dozier, 1998). Among 84 foster
parent-child dyads, foster mothers who had fostered more children previously
showed lower levels of commitment than did foster mothers who had fostered fewer
children. Commitment also was associated with child age at placement, with foster
parents showing higher levels of commitment to children who were placed at
younger ages than to children who were placed at older ages. Commitment predicted
the stability of the relationship, with higher levels of commitment associated
with a greater likelihood of adoption or long-term placement. These results
suggest the importance of designing a child welfare system that will enhance
caregivers' ability to commit to the children for whom they provide care.
PMID- 17043320
TI - Service outcomes in physical and sexual abuse cases: a comparison of child
advocacy center-based and standard services.
AB - Child Advocacy Centers (CACs) were developed to improve on child abuse
investigative services provided by child protective service (CPS) agencies.
However, until very recently, there has been little research comparing CAC-based
procedures and outcomes to those in CPS investigations not based in CACs. The
current study tracked 76 child abuse cases that were reported to authorities and
investigated through either a private, not-for-profit CAC or typical CPS services
in a mid-south rural county. Comparisons between CAC and CPS cases were made in
terms of involvement of local law enforcement in the investigation, provision of
medical exams, abuse substantiation rates, mental health referrals, prosecution
referrals, and conviction rates. Analyses revealed higher rates of law
enforcement involvement, medical examinations, and case substantiation in the CAC
based cases compared to the CPS cases. Despite limitations due to sample size and
non-randomization, this study found preliminary support for the assumptions
underlying the establishment of CACs.
PMID- 17043319
TI - Adolescent girls' offending and health-risking sexual behavior: the predictive
role of trauma.
AB - Several studies have highlighted high levels of risk for girls who have been
exposed to traumatic experiences, but little is known about the exact
relationship between traumatic experiences and problems with delinquency and
health-risking sexual behavior (e.g., precipitory and/or exacerbatory roles).
However, numerous short- and long-term detrimental effects have been linked to
trauma, delinquency, and health-risking sexual behavior. The utility of
diagnostic and experiential trauma measures in predicting the greatest risk for
poor outcomes for delinquent girls was examined in this study. Results indicate
that the experiential measures of trauma (cumulative and composite trauma scores)
significantly predicted adolescent offending and adolescent health-risking sexual
behavior, whereas the diagnostic measures of trauma (full and partial diagnostic
criteria) did not.
PMID- 17043321
TI - Pediatrician characteristics associated with child abuse identification and
reporting: results from a national survey of pediatricians.
AB - Pediatrician experience with child protective services (CPS) and factors
associated with identifying and reporting suspected child physical abuse were
examined by a survey of members of the American Academy of Pediatrics (AAP).
Respondents provided information about their demographics and experience,
attitudes and practices with child abuse. They indicated their diagnosis and
management of a child in a purposely ambiguous clinical vignette. Pediatricians
who had received recent child abuse education were more confident in their
ability to identify and manage child abuse. High confidence in ability to manage
child abuse and positive attitude about domestic violence screening and value of
anticipatory guidance predicted that pediatricians would have high suspicion that
the child in the vignette was abused and that they would report the child to CPS.
Future efforts to improve medical intervention in child abuse should focus on
physician attitudes and experience, as well as cognitive factors.
PMID- 17043322
TI - An elaboration on the distinction between controversial parenting and therapeutic
practices versus developmentally appropriate attachment parenting: a comment on
the APSAC Task Force report.
PMID- 17043323
TI - The report of the APSAC Task Force on Attachment Therapy, Reactive Attachment
Disorder, and Attachment Problems.
PMID- 17043324
TI - The report of the APSAC Task Force on Attachment Therapy, Reactive Attachment
Disorder, and Attachment Problems.
PMID- 17043325
TI - The report of the APSAC Task Force on Attachment Therapy, Reactive Attachment
Disorder, and Attachment Problems.
PMID- 17043327
TI - To breathe or not to breathe: the respiratory muscles and COPD.
PMID- 17043328
TI - Development of an in vitro model for study of the efficacy of ischemic
preconditioning in human skeletal muscle against ischemia-reperfusion injury.
AB - Ischemia-reperfusion (I/R) injury causes skeletal muscle infarction and ischemic
preconditioning (IPC) augments ischemic tolerance in animal models. To date, this
has not been demonstrated in human skeletal muscle. This study aimed to develop
an in vitro model to investigate the efficacy of simulated IPC in human skeletal
muscle. Human skeletal muscle strips were equilibrated in oxygenated Krebs
Henseleit-HEPES buffer (37 degrees C). Aerobic and reperfusion phases were
simulated by normoxic incubation and reoxygenation, respectively. Ischemia was
simulated by hypoxic incubation. Energy store, cell viability, and cellular
injury were assessed using ATP, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H
tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) assays, respectively.
Morphological integrity was assessed using electron microscopy. Studies were
designed to test stability of the preparation (n = 5-11) under normoxic
incubation over 24 h; the effect of 1, 2, 3, 4, or 6 h hypoxia followed by 2 h of
reoxygenation; and the protective effect of hypoxic preconditioning (HPC; 5 min
of hypoxia/5 min of reoxygenation) before 3 h of hypoxia/2 h of reoxygenation.
Over 24 h of normoxic incubation, muscle strips remained physiologically intact
as assessed by MTT, ATP, and LDH assays. After 3 h of hypoxia/2 h of
reoxygenation, MTT reduction levels declined to 50.1 +/- 5.5% (P < 0.05). MTT
reduction levels in HPC (82.3 +/- 10.8%) and normoxic control (81.3 +/- 10.2%)
groups were similar and higher (P < 0.05) than the 3 h of hypoxia/2 h of
reoxygenation group (45.2 +/- 5.8%). Ultrastructural morphology was preserved in
normoxic and HPC groups but not in the hypoxia/reoxygenation group. This is the
first study to characterize a stable in vitro model of human skeletal muscle and
to demonstrate a protective effect of HPC in human skeletal muscle against
hypoxia/reoxygenation-induced injury.
PMID- 17043329
TI - Contralateral effects of unilateral strength training: evidence and possible
mechanisms.
AB - If exercises are performed to increase muscle strength on one side of the body,
voluntary strength can increase on the contralateral side. This effect, termed
the contralateral strength training effect, is usually measured in homologous
muscles. Although known for over a century, most studies have not been designed
well enough to show a definitive transfer of strength that could not be explained
by factors such as familiarity with the testing. However, an updated meta
analysis of 16 properly controlled studies (range 15-48 training sessions) shows
that the size of the contralateral strength training effect is approximately 8%
of initial strength or about half the increase in strength of the trained side.
This estimate is similar to results of a large, randomized controlled study of
training for the elbow flexors (contralateral effect of 7% initial strength or
one-quarter of the effect on the trained side). This is likely to reflect
increased motoneuron output rather than muscular adaptations, although most
methods are insufficiently sensitive to detect small muscle contributions. Two
classes of central mechanism are identified. One involves a "spillover" to the
control system for the contralateral limb, and the other involves adaptations in
the control system for the trained limb that can be accessed by the untrained
limb. Cortical, subcortical and spinal levels are all likely to be involved in
the "transfer," and none can be excluded with current data. Although the size of
the effect is small and may not be clinically significant, study of the
phenomenon provides insight into neural mechanisms associated with exercise and
training.
PMID- 17043330
TI - Counterpoint: the classical Guyton view that mean systemic pressure, right atrial
pressure, and venous resistance govern venous return is not correct.
PMID- 17043333
TI - The classical Guyton view that mean systemic pressure, right atrial pressure, and
venous resistance govern venous return is/is not correct.
PMID- 17043334
TI - Summaries for patients. Can antibiotics improve the symptoms of the irritable
bowel syndrome?
PMID- 17043335
TI - Summaries for patients. What happens to patients during the year following
treatment for sexually transmitted infections? How well does antibiotic treatment
work?
PMID- 17043336
TI - Summaries for patients. Mild thyroid dysfunction is not associated with anxiety,
depression, or cognition in the elderly.
PMID- 17043337
TI - The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the
irritable bowel syndrome: a randomized trial.
AB - BACKGROUND: Alterations in gut flora may be important in the pathophysiology of
the irritable bowel syndrome (IBS). OBJECTIVE: To determine whether the
nonabsorbed antibiotic rifaximin is more effective than placebo in reducing
symptoms in adults with IBS. DESIGN: Double-blind, randomized, placebo-controlled
study. SETTING: 2 tertiary care medical centers. PARTICIPANTS: 87 patients who
met Rome I criteria for IBS and were enrolled from December 2003 to March 2005.
INTERVENTIONS: Participants who met enrollment criteria were randomly assigned to
receive 400 mg of rifaximin 3 times daily for 10 days (n = 43) or placebo (n =
44). Eighty participants completed rifaximin therapy or placebo, and follow-up
data were available for at least 34 participants per study group at any time
point thereafter. MEASUREMENTS: A questionnaire was administered before treatment
and 7 days after treatment. The primary outcome was global improvement in IBS.
Patients were then asked to keep a weekly symptom diary for 10 weeks. RESULTS:
Over the 10 weeks of follow-up, rifaximin resulted in greater improvement in IBS
symptoms (P = 0.020). In addition, rifaximin recipients had a lower bloating
score after treatment. LIMITATIONS: The major limitations of the study were its
modest sample size and short duration and that most patients were from 1 center.
CONCLUSIONS: Rifaximin improves IBS symptoms for up to 10 weeks after the
discontinuation of therapy.
PMID- 17043338
TI - High incidence of new sexually transmitted infections in the year following a
sexually transmitted infection: a case for rescreening.
AB - BACKGROUND: Studies show 11% to 15% of women treated for Chlamydia trachomatis
are reinfected 3 to 4 months after treatment, suggesting the need for
rescreening. There is little information on infections among men, infections with
Neisseria gonorrhoeae or Trichomonas vaginalis, or long-term follow-up.
OBJECTIVE: To determine the incidence of new sexually transmitted infections
during the year after a visit to a sexually transmitted disease (STD) clinic and
associated risk factors. DESIGN: Secondary analysis of data from a randomized,
controlled trial (RESPECT-2). SETTING: 3 urban STD clinics. PATIENTS: Sexually
active patients enrolled in an HIV prevention counseling trial. MEASUREMENTS:
Patient characteristics at the initial visit; behaviors during follow-up; and new
infections with C. trachomatis, N. gonorrhoeae, or T. vaginalis (women only)
detected during 4 scheduled return visits and any other interim visits. RESULTS:
2419 persons had 8129 three-month follow-up intervals. Among 1236 women, 25.8%
had 1 or more new infections (11.9% acquired C. trachomatis, 6.3% acquired N.
gonorrhoeae, and 12.8% acquired T. vaginalis); among 1183 men, 14.7% had 1 or
more new infections (9.4% acquired C. trachomatis, and 7.1% acquired N.
gonorrhoeae). Black persons and those with sexually transmitted infections at
baseline were at highest risk for recurrent infection (adjusted odds ratio, 2.5
and 2.4, respectively). For persons infected at baseline, the risk for infection
was high at 3 and 6 months (16.3 per 100 three-month intervals) and remained high
at 9 and 12 months (12.0 per 100 three-month intervals). Most (67.2%) infections
were diagnosed during study-related visits, and 66.2% of these patients reported
no symptoms. LIMITATIONS: Because patients were recruited from STD clinics,
results may not be generalizable. CONCLUSIONS: Men and women who receive
diagnoses of C. trachomatis, N. gonorrhoeae, or T. vaginalis infections should
return in 3 months for rescreening because they are at high risk for new
asymptomatic sexually transmitted infections. Although single-dose therapy may
adequately treat the infection, it often does not adequately treat the patient.
PMID- 17043339
TI - Is subclinical thyroid dysfunction in the elderly associated with depression or
cognitive dysfunction?
AB - BACKGROUND: Widespread use of automated sensitive assays for thyroid hormones and
thyroid-stimulating hormone (TSH) has increased identification of mild thyroid
dysfunction, especially in elderly patients. The clinical significance of this
dysfunction, however, remains uncertain, and associations with cognitive
impairment, depression, and anxiety are unconfirmed. OBJECTIVE: To determine the
association between mild thyroid dysfunction and cognition, depression, and
anxiety in elderly persons. DESIGN: Cross-sectional study. Associations were
explored through mixed-model analyses. SETTING: Primary care practices in central
England. PATIENTS: 5865 patients 65 years of age or older with no known thyroid
disease who were recruited from primary care registers. MEASUREMENTS: Serum TSH
and free thyroxine (T4) were measured. Depression and anxiety were assessed by
using the Hospital Anxiety and Depression Scale (HADS), and cognitive functioning
was established by using the Middlesex Elderly Assessment of Mental State and the
Folstein Mini-Mental State Examination. Comorbid conditions, medication use, and
sociodemographic profiles were recorded. RESULTS: 295 patients met the criteria
for subclinical thyroid dysfunction (127 were hyperthyroid, and 168 were
hypothyroid). After confounding variables were controlled for, statistically
significant associations were seen between anxiety (HADS score) and TSH level (P
= 0.013) and between cognition and both TSH and free T4 levels. The magnitude of
these associations lacked clinical relevance: A 50-mIU/L increase in the TSH
level was associated with a 1-point reduction in the HADS anxiety score, and a 1
point increase in the Mini-Mental State Examination score was associated with an
increase of 50 mIU/L in the TSH level or 25 pmol/L in the free T4 level.
LIMITATIONS: Because of the low participation rate, low prevalence of subclinical
thyroid dysfunction, and other unidentified recruitment biases, participants may
not be representative of the elderly population. CONCLUSIONS: After the
confounding effects of comorbid conditions and use of medication were controlled
for, subclinical thyroid dysfunction was not associated with depression, anxiety,
or cognition.
PMID- 17043340
TI - Device-associated nosocomial infections in 55 intensive care units of 8
developing countries.
AB - BACKGROUND: Health care-associated infections from invasive medical devices in
the intensive care unit (ICU) are a major threat to patient safety. Most
published studies of ICU-acquired infections have come from industrialized
western countries. In a Centers for Disease Control and Prevention (CDC) National
Nosocomial Infections Surveillance (NNIS) System report, the U.S. pooled mean
rates of central venous catheter (CVC)-related bloodstream infections, ventilator
associated pneumonia, and catheter-associated urinary tract infections were 4.0
per 1000 CVC days, 5.4 per 1000 mechanical ventilator days, and 3.9 per Foley
catheter days, respectively. OBJECTIVE: To ascertain the incidence of device
associated infections in the ICUs of developing countries. DESIGN: Multicenter,
prospective cohort surveillance of device-associated infection by using the CDC
NNIS System definitions. SETTING: 55 ICUs of 46 hospitals in Argentina, Brazil,
Colombia, India, Mexico, Morocco, Peru, and Turkey that are members of the
International Nosocomial Infection Control Consortium (INICC). MEASUREMENTS:
Rates of device-associated infection per 100 patients and per 1000 device days.
RESULTS: During 2002-2005, 21,069 patients who were hospitalized in ICUs for an
aggregate 137,740 days acquired 3095 device-associated infections for an overall
rate of 14.7% or 22.5 infections per 1000 ICU days. Ventilator-associated
pneumonia posed the greatest risk (41% of all device-associated infections or
24.1 cases [range, 10.0 to 52.7 cases] per 1000 ventilator days), followed by CVC
related bloodstream infections (30% of all device-associated infections or 12.5
cases [range, 7.8 to 18.5 cases] per 1000 catheter days) and catheter-associated
urinary tract infections (29% of all device-associated infections or 8.9 cases
[range, 1.7 to 12.8 cases] per 1000 catheter days). Notably, 84% of
Staphylococcus aureus infections were caused by methicillin-resistant strains,
51% of Enterobacteriaceae isolates were resistant to ceftriaxone, and 59% of
Pseudomonas aeruginosa isolates were resistant to fluoroquinolones. The crude
mortality rate for patients with device-associated infections ranged from 35.2%
(for CVC-associated bloodstream infection) to 44.9% (for ventilator-associated
pneumonia). LIMITATIONS: These initial data are not adequate to represent any
entire country, and likely variations in the efficiency of surveillance and
institutional resources may have affected the rates that were detected.
CONCLUSIONS: Device-associated infections in the ICUs of these developing
countries pose greater threats to patient safety than in U.S. ICUs. Active
infection control programs that perform surveillance of infection and implement
guidelines for prevention can improve patient safety and must become a priority
in every country.
PMID- 17043341
TI - Graduate medical education and patient safety: a busy--and occasionally hazardous
-intersection.
AB - A patient admitted to a teaching hospital with a mild episode of acute
pancreatitis initially improved, but then her condition deteriorated and she
subsequently died. The initial deterioration probably reflected bowel
obstruction, as shown on an abdominal radiograph that an on-call intern forgot to
review. This diagnostic delay was compounded by poor communication that resulted
in a medical student inserting a feeding tube--rather than a nasogastric tube--to
decompress the bowel, followed by failure to recognize how ill the patient had
become. The case highlights the hazards of patient handoffs as well as the
importance of clear communication techniques and knowing when to ask for help.
The discussion also shows the vicious circle that results when attending
physicians fail to provide effective supervision: Not only is safety compromised
but trainees lose the experience of being supervised. Consequently, trainees have
no models of effective supervision on which to draw when they become supervisors.
They then fall into the same trap as those who taught them, busying themselves
with direct patient care and providing supervision only as time allows.
PMID- 17043342
TI - Narrative review: reperfusion strategies for ST-segment elevation myocardial
infarction.
AB - Optimal treatment for ST-segment elevation myocardial infarction depends on early
diagnosis and rapid selection of the appropriate reperfusion strategy. Primary
percutaneous coronary intervention (PCI) is the preferred reperfusion strategy at
PCI-capable hospitals. For hospitals without PCI capability, there are 2
reperfusion strategies, primary PCI and thrombolytic therapy, which are both
supported by clinical evidence and national guidelines. Transferring patients for
primary PCI may cause delays and requires established, proven protocols, systems,
and networks to achieve minimal door-to-balloon times. The authors review the
available data and present a systematic, evidence-based approach in a simple
framework to enable noncardiovascular and cardiovascular physicians to select the
optimal reperfusion strategy. The framework is based on available data from
clinical trials and local circumstances from clinical practice by incorporating
duration of symptoms (fixed ischemia time) and anticipated transport delays to a
PCI-capable facility (incurred ischemia time).
PMID- 17043343
TI - Update in cardiology.
PMID- 17043344
TI - Treatment for bacterial overgrowth in the irritable bowel syndrome.
PMID- 17043345
TI - Quality grand rounds: the case for patient safety.
PMID- 17043346
TI - Green tea, coffee, and diabetes.
PMID- 17043347
TI - Green tea, coffee, and diabetes.
PMID- 17043349
TI - Green tea, coffee, and diabetes.
PMID- 17043350
TI - Green tea, coffee, and diabetes.
PMID- 17043351
TI - Clinicopathologic characteristics and outcome of diffuse large B-cell lymphomas
presenting with an associated low-grade component at diagnosis.
AB - PURPOSE: Some diffuse large B-cell lymphomas (DLBCL) present at diagnosis with
associated morphologic features of small B-cell non-Hodgkin's lymphoma (NHL) and
may arise from the transformation of a previously unknown indolent low-grade
lymphoma. The characteristics and prognosis of these particular DLBCL are not
well known. PATIENTS AND METHODS: The strict morphologic review of consecutive
DLBCL patients diagnosed over 12 years in our department (Hematology Department,
Centre Hospitalier Lyon-Sud, Lyon, France) allowed to retrieve 60 DLBCL that
could be have occurred from the transformation of marginal zone B-cell NHL (32
patients), follicular NHL (22 patients), and small lymphocytic NHL (6 patients).
We compared them to 180 matched patients of de novo DLBCL. RESULTS: Patients
median age was 55 years and presented the following clinical characteristics:
poor performance status in 33%, disseminated disease in 97%, more than one
extranodal site in 50%, and increased lactate dehydrogenase level in 55%.
Complete remission with multidrug chemotherapy regimens was achieved in 60% of
the patients, but 48% relapsed: 28% with aggressive and 20% with indolent
histology, respectively. Overall survival (OS) and freedom-from-progression rates
at 5 years were 57% and 33%, respectively. The matched-control analysis showed
that patients with transformed NHL at diagnosis had lower complete response to
chemotherapy (P = .004) and higher progression rate (P = .03), whereas no
difference was observed in OS (P = .21). CONCLUSION: Compared to de novo DLBCL,
transformed NHL at diagnosis have similar overall survival but lower complete
response to initial treatment and higher risk of indolent relapses.
PMID- 17043352
TI - Post-transcriptional destabilization of p21cip1 by protein kinase C in
fibroblasts.
AB - p21(cip1) inhibits S phase entry by binding to cyclin-cdk2 (cyclin-dependent
kinase-2) complexes. The levels of p21(cip1) are rapidly induced after mitogenic
stimulation of quiescent fibroblasts and then down-regulate as the cells reach
late G(1) phase and activate cyclin E-cdk2. In this study, we have shown that
pharmacological inhibition of protein kinase C (PKC), expression of dominant
negative PKCdelta, or knockdown of PKCdelta with small interfering RNA elevates
p21(cip1) protein levels in mouse embryo fibroblasts. This effect is selective,
post-transcriptional, and proteasome-dependent but distinct from previously
identified post-transcriptional control mechanisms involving cyclin D1 and Skp2.
PKCdelta inhibition results in a reduced entry into S phase, and this effect is
not detected in p21(cip1)-null cells. Thus, post-transcriptional destabilization
of p21(cip1) appears to be a major mitogenic effect of PKCdelta in fibroblasts.
PMID- 17043353
TI - Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin
ligase gp78.
AB - Insig-1 and Insig-2, closely related endoplasmic reticulum membrane proteins,
mediate transcriptional and post-transcriptional mechanisms that assure
cholesterol homeostasis through their sterol-induced binding to Scap (SREBP
cleavage-activating protein) and 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Recent studies show that Insig-1 (but not Insig-2) is ubiquitinated and rapidly
degraded when cells are depleted of sterols. Conversely, ubiquitination of Insig
1 is blocked, and the protein is stabilized when intracellular sterols
accumulate. Here, we report that the ubiquitin ligase gp78, which binds with much
higher affinity to Insig-1 than Insig-2, is required for ubiquitination and
degradation of Insig-1 in sterol-depleted cells. Sterols prevent Insig-1
ubiquitination and degradation by displacing gp78 from Insig-1, an event that
results from sterol-induced binding of Scap to Insig-1. In addition to providing
a mechanism for sterol-regulated degradation of Insig-1, these results help to
explain why Scap is subject to endoplasmic reticulum retention upon Insig-1
binding, whereas 3-hydroxy-3-methylglutaryl coenzyme A reductase is ubiquitinated
and degraded.
PMID- 17043354
TI - Deletion of core fucosylation on alpha3beta1 integrin down-regulates its
functions.
AB - The core fucosylation (alpha1,6-fucosylation) of glycoprotein is widely
distributed in mammalian tissues. Recently alpha1,6-fucosylation has been further
reported to be very crucial by the study of alpha1,6-fucosyltransferase (Fut8)
knock-out mice, which shows the phenotype of emphysema-like changes in the lung
and severe growth retardation. In this study, we extensively investigated the
effect of core fucosylation on alpha3beta1 integrin and found for the first time
that Fut8 makes an important contribution to the functions of this integrin. The
role of core fucosylation in alpha3beta1 integrin-mediated events has been
studied by using Fut8(+/+) and Fut8(-/-) embryonic fibroblasts, respectively. We
found that the core fucosylation of alpha3beta1 integrin, the major receptor for
laminin 5, was abundant in Fut8(+/+) cells but was totally abolished in Fut8(-/-)
cells, which was associated with the deficient migration mediated by alpha3beta1
integrin in Fut8(-/-) cells. Moreover integrin-mediated cell signaling was
reduced in Fut8(-/-) cells. The reintroduction of Fut8 potentially restored
laminin 5-induced migration and intracellular signaling. Collectively, these
results suggested that core fucosylation is essential for the functions of
alpha3beta1 integrin.
PMID- 17043356
TI - A Mitogen-activated protein kinase kinase kinase mediates reactive oxygen species
homeostasis in Arabidopsis.
AB - Mitogen-activated protein kinase kinase kinases (MAPKKKs) play key roles in intra
and extracellular signaling in eukaryotes. Here we report that the MAPKKK MEKK1
regulates redox homeostasis in Arabidopsis. We show that MEKK1-deficient plants
are misregulated in the expression of a number of genes involved in cellular
redox control and accumulate reactive oxygen species (ROS). Most strikingly,
homozygous mekk1 mutant plants exhibit a lethal phenotype when developing true
leaves. MEKK1 kinase activity and protein stability was regulated by H(2)O(2) in
a proteasome-dependent manner and mekk1 plants were compromised in ROS-induced
MAPK MPK4 activation. Whereas mpk3 and mpk6 knock out plants showed no defects in
development or changes in redox control genes, mpk4 null mutant shared several
phenotypic and transcript profile features with mekk1 plants. In agreement with
the concept that ROS negatively regulates auxin responses in plants, mekk1 and
mpk4 mutants show reduced expression of several auxin-inducible marker genes.
Overall, our data defines MPK4 as downstream target of MEKK1 and show that MEKK1
functions in integrating ROS homeostasis with plant development and hormone
signaling.
PMID- 17043355
TI - The tandem BRCT domain of 53BP1 is not required for its repair function.
AB - 53BP1 plays an important role in cellular response to DNA damage. It is thought
to be the mammalian homologue of budding yeast Rad9 and/or fission yeast Crb2.
Rad9/Crb2 are bona fide checkpoint proteins whose activation requires their
corresponding C-terminal tandem BRCT (BRCA1 C-terminal) motifs, which mediate
their oligomerization and phosphorylation at multiple sites following DNA damage.
Here we show that the function of human 53BP1 similarly depends on its
oligomerization and phosphorylation at multiple sites but in a BRCT domain
independent manner. Moreover, unlike its proposed yeast counterparts, human 53BP1
only has limited checkpoint functions but rather acts as an adaptor in the repair
of DNA double strand breaks. This difference in function may reflect the higher
complexity of the DNA damage response network in metazoa including the evolution
of other BRCT domain-containing proteins that may have functions redundant or
overlapping with those of 53BP1.
PMID- 17043357
TI - Nucleocytoplasmic shuttling of the retinoblastoma tumor suppressor protein via
Cdk phosphorylation-dependent nuclear export.
AB - The retinoblastoma (RB) tumor suppressor protein is a negative regulator of cell
proliferation that is functionally inactivated in the majority of human tumors.
Elevated Cdk activity via RB pathway mutations is observed in virtually every
human cancer. Thus, Cdk inhibitors have tremendous promise as anticancer agents
although detailed mechanistic knowledge of their effects on RB function is needed
to harness their full potential. Here, we illustrate a novel function for Cdks in
regulating the subcellular localization of RB. We present evidence of significant
cytoplasmic mislocalization of ordinarily nuclear RB in cells harboring Cdk4
mutations. Our findings uncover a novel mechanism to circumvent RB-mediated
growth suppression by altered nucleocytoplasmic trafficking via the Exportin1
pathway. Cytoplasmically mislocalized RB could be efficiently confined to the
nucleus by inhibiting the Exportin1 pathway, reducing Cdk activity, or mutating
the Cdk-dependent phosphorylation sites in RB that result in loss of RB-Exportin1
association. Thus RB-mediated tumor suppression can be subverted by
phosphorylation-dependent enhancement of nuclear export. These results support
the notion that tumor cells can modulate the protein transport machinery thereby
making the protein transport process a viable therapeutic target.
PMID- 17043358
TI - Association of focal adhesion kinase with tuberous sclerosis complex 2 in the
regulation of s6 kinase activation and cell growth.
AB - Tuberous sclerosis complex 1 (TSC1) and TSC2 tumor suppressor proteins have been
shown to negatively regulate cell growth through inhibition of the mammalian
target of rapamycin (mTOR) pathway. Focal adhesion kinase (FAK) is a cytoplasmic
tyrosine kinase that plays a critical role in integrin signaling. Here we
identify a novel interaction between FAK and TSC2 and show that TSC2 is
phosphorylated by FAK. Furthermore, we show that overexpression of FAK kinase
dead mutant inhibits the phosphorylation of ribosomal S6 kinase (S6K) and
eukaryotic initiation factor 4E-binding protein-1, two key mTOR (mammalian target
of rapamycin) downstream targets, and negatively regulates the cell size and that
FAK regulation of S6K phosphorylation is through TSC2. Finally, we provide data
that FAK plays a positive role in cell adhesion-induced S6K phosphorylation,
whereas TSC2 is required for cell suspension-induced S6K inactivation. Together,
these results suggest that FAK might regulate S6K activation and cell size
through its interaction with and phosphorylation of TSC2 and also provide a
previously unappreciated role of TSC2 in the regulation of mTOR signaling by cell
adhesion.
PMID- 17043359
TI - Mechanism of regulation of prokaryotic tubulin-like GTPase FtsZ by membrane
protein EzrA.
AB - At initiation of cell division, FtsZ, a tubulin-like GTPase, assembles into a so
called Z-ring structure at the site of division. The formation of Z ring is
negatively regulated by EzrA, which ensures only one ring at the midcell per cell
cycle. The mechanism leading to the negative regulation of Z-ring formation by
EzrA has been analyzed. Our data reveal that the interaction between EzrA and
FtsZ not only reduces the GTP-binding ability of FtsZ but also accelerates the
rate of GTP hydrolysis, both of which are unfavorable for the polymerization of
FtsZ. Moreover, the acceleration in rate of GTP hydrolysis by EzrA is attributed
to stabilization of the transition state for GTP hydrolysis and reduction in the
affinity of GDP for FtsZ. Clearly, EzrA is able to modify the GTP hydrolysis
cycle of FtsZ. On the basis of these results, a model for how EzrA acts to
negatively regulate Z-ring formation is proposed.
PMID- 17043360
TI - Interactions between the RNA interference effector protein Ago1 and 14-3-3
proteins: consequences for cell cycle progression.
AB - The Argonaute family member Ago1 is required for formation of pericentric
heterochromatin and small interfering RNA (siRNA)-mediated post-transcriptional
gene silencing in the fission yeast Schizosaccharomyces pombe. In addition, we
have recently demonstrated that Ago1 function is required for enactment of cell
cycle checkpoints (Carmichael, J. B., Provost, P., Ekwall, K., and Hobman, T. C.
(2004) Mol. Biol. Cell 15, 1425-1435). Here, we provide evidence that the amino
terminus of Ago1 binds to proteins that function in cell cycle regulation
including 14-3-3 proteins. Interestingly, the amino terminus of human Ago2, the
endonuclease that cleaves siRNA-targeted mRNAs, was also demonstrated to bind 14
3-3 proteins. Overexpression of the Ago1 amino terminus in yeast resulted in cell
cycle delay at the G(2)/M boundary. Further investigation revealed that nuclear
import of the mitosis-inducing phosphatase Cdc25 is inhibited by overexpression
of the Ago1 amino terminus. Under these conditions, we found that the cyclin
dependent kinase Cdc2 is constitutively phosphorylated on tyrosine 15, thereby
reducing the activity of this kinase, a situation that delays entry into mitosis.
We hypothesize that 14-3-3 proteins are required for Argonaute protein functions
in cell cycle and/or gene-silencing pathways.
PMID- 17043361
TI - Identification and stage-specific association with the translational apparatus of
TbZFP3, a CCCH protein that promotes trypanosome life-cycle development.
AB - The post-transcriptional control of gene expression is becoming increasingly
important in the understanding of regulated events in eukaryotic cells. The
parasitic kinetoplastids have a unique reliance on such processes, because their
genome is organized into polycistronic transcription units in which adjacent
genes are not coordinately regulated. Indeed, the number of RNA-binding proteins
predicted to be encoded in the genome of kinetoplastids is unusually large,
invoking the presence of unique RNA regulators dedicated to gene expression in
these evolutionarily ancient organisms. Here, we report that a small CCCH zinc
finger protein, TbZFP3, enhances development between life-cycle stages in
Trypanosoma brucei. Moreover, we demonstrate that this protein interacts both
with the translational machinery and with other small CCCH proteins previously
implicated in trypanosome developmental control. Antibodies to this protein also
co-immunoprecipitate EP procyclin mRNA and encode the major surface antigen of
insect forms of T. brucei. Strikingly, although TbZFP3 is constitutively
expressed, it exhibits developmentally regulated association with polyribosomes,
and mutational analysis demonstrates that this association is essential for the
expression of phenotype. TbZFP3 is therefore a novel regulator of developmental
events in kinetoplastids that acts at the level of the post-transcriptional
control of gene expression.
PMID- 17043362
TI - Origin and goals of the "Gender Symmetry" Workshop.
AB - This article provides a brief account of the historical background to the Gender
Symmetry Workshop and describes its major goals. The Workshop is a successor to
an earlier workshop co-sponsored by the Centers for Disease Control and
Prevention and the National Institute of Justice in 1998, namely the Workshop on
Building Data Systems for Monitoring and Responding to Violence Against Women.
Some key issues that were left unresolved in that workshop provided the rationale
for holding the Gender Symmetry Workshop. The Workshop was designed to cover
three topic areas: (1) a typology of violence, (2) measurement issues, and (3)
women's use of violence.
PMID- 17043363
TI - Conflict and control: gender symmetry and asymmetry in domestic violence.
AB - Four types of individual partner violence are identified based on the dyadic
control context of the violence. In intimate terrorism, the individual is violent
and controlling, the partner is not. In violent resistance, the individual is
violent but not controlling; the partner is the violent and controlling one. In
situational couple violence, although the individual is violent, neither the
individual nor the partner is violent and controlling. In mutual violent control,
the individual and the partner are violent and controlling. Evidence is presented
that situational couple violence dominates in general surveys, intimate terrorism
and violent resistance dominate in agency samples, and this is the source of
differences across studies with respect to the gender symmetry of partner
violence. An argument is made that if we want to understand partner violence,
intervene effectively in individual cases, or make useful policy recommendations,
we must make these distinctions in our research.
PMID- 17043364
TI - Commentary on Johnson's "conflict and control: gender symmetry and asymmetry in
domestic violence".
PMID- 17043365
TI - The development of a theory of women's use of violence in intimate relationships.
AB - Reports have appeared in the popular press in recent years concluding that women
are just as violent as men. These reports stem from acontextual survey studies
comparing prevalence rates of women's and men's physical violence. The authors
contend that the above conclusion is simplistic and misleading, and that a
theoretical framework that embeds women's violence in the context in which it
occurs is sorely needed. This article proposes a model that includes women's
violence in the context of their victimization by male partners, motivations for
violent behavior and how they cope with relationship problems, experiences of
childhood trauma, and outcomes of depression, anxiety, posttraumatic stress
disorder, and substance use. The model is then examined within the context of
gender, race, and class. The cultural context of domestic violence for African
American and Latina women is reviewed. This literature reinforces the need to
place women's violence in a broader sociocultural context.
PMID- 17043366
TI - Commentary on Swan and Snow's "the development of a theory of women's use of
violence in intimate relationships".
PMID- 17043367
TI - Beyond frequency and severity: development and validation of the brief coercion
and conflict scales.
AB - Responding to calls for improved measurement in the field of domestic violence,
this paper reports the development and initial validation of the Brief Coercion
and Conflict Scales in a sample of incarcerated women. Confirmatory factor
analyses tested the scales hypothesized structure and supported coercion and
conflict as moderately and positively related but distinct constructs. Although
women reported experiencing both conflict and coercion in their most recent
relationship before incarceration, they reported that their experiences were more
often marked by interpersonal conflict than by coercion. Further, the coercion
and conflict scales differentially predicted women's behavioral and psychological
responses to abuse. Only coercion consistently predicted strategic responses and
posttraumatic stress symptoms. Overall, findings support the instrument as a
viable option, but further psychometric evaluation of internal and external
validity with additional samples is warranted.
PMID- 17043368
TI - Commentary on Cook and Goodman's "beyond frequency and severity: development and
validation of the brief coercion and conflict scales".
PMID- 17043369
TI - Future directions.
PMID- 17043370
TI - Future research on gender symmetry in physical assaults on partners.
AB - In the light of evidence from about 200 studies showing gender symmetry in
perpetration of partner assault, research can now focus on why gender symmetry is
predominant and on the implications of symmetry for primary prevention and
treatment of partner violence. Progress in such research is handicapped by a
number of problems: (1) Insufficient empirical research and a surplus of
discussion and theory, (2) Blinders imposed by commitment to a single causal
factor theory-patriarchy and male dominance-in the face of overwhelming evidence
that this is only one of a multitude of causes, (3) Research purporting to
investigate gender differences but which obtains data on only one gender, (4)
Denial of research grants to projects that do not assume most partner violence is
by male perpetrators, (5) Failure to investigate primary prevention and treatment
programs for female offenders, and (6) Suppression of evidence on female
perpetration by both researchers and agencies.
PMID- 17043371
TI - Increasing parasitic diseases in Japan.
PMID- 17043372
TI - Medical check-up findings characteristic of smokers: aimed at improving smoking
cessation interventions by physicians.
AB - OBJECTIVE: The purpose of this study was to elucidate the medical check-up
findings associated with smoking habit, which medical professionals, particularly
physicians, should use for the promotion of quitting smoking. METHODS: In 6,215
male and 1,627 female employees who participated in annual medical check-up, we
compared the results of each test between smokers and nonsmokers. RESULTS: Many
results were significantly different between smokers and nonsmokers in both males
and females. Among them, the hematocrit, leukocyte count, and levels of
hemoglobin and triglyceride were significantly higher, the level of high-density
lipoprotein cholesterol was significantly lower, and the frequencies of positive
urinary occult blood and hearing loss were significantly higher in male smokers
than in male nonsmokers. Furthermore, the hematocrit, leukocyte count, positive
urinary occult blood, hearing loss, and levels of hemoglobin, triglyceride, and
high-density lipoprotein cholesterol showed significant trends for male
nonsmoker, and light, moderate, and heavy male smokers, that is, significant
associations with larger numbers of cigarettes smoked per day. CONCLUSION: Not
only polycythemia and low high-density lipoprotein cholesterol level but also
high leukocyte count, hearing loss, positive urinary occult blood, and high
triglyceride level are smoking-related abnormal findings. In the medical check
up, medical professionals should inform smokers of these data and encourage them
to quit smoking.
PMID- 17043373
TI - Beneficial effect of polymyxin B-immobilized fiber column (PMX) hemoperfusion
treatment on acute exacerbation of idiopathic pulmonary fibrosis.
AB - OBJECTIVE: This study was aimed to investigate the effect of polymyxin B
immobilized fiber column (PMX) hemoperfusion treatment on the acute exacerbation
of idiopathic pulmonary fibrosis (IPF). PATIENTS AND METHODS: Six patients with a
clinical diagnosis of idiopathic pulmonary fibrosis (IPF) who developed acute
exacerbation were included in this study. Although five of six patients were
treated with high-dose corticosteroid therapy, mechanical ventilation was
necessary for all six patients due to severe respiratory failure. Blood endotoxin
levels were undetectable in all patients. PMX treatment was performed on these
six patients. RESULTS: In four of six patients, alveolar-arterial difference of
oxygen (AaDO(2)), serum KL-6 and lactate dehydrogenase (LDH) were improved after
PMX treatment. These four patients were successfully weaned from mechanical
ventilation and survived more than 30 days after the initial PMX treatment.
CONCLUSION: These data suggest a potential beneficial effect of PMX treatment on
acute exacerbation of IPF.
PMID- 17043374
TI - Relationship between metabolic syndrome and cigarette smoking in the Japanese
population.
AB - OBJECTIVE: We investigated the link between metabolic syndrome and cigarette
smoking in the Japanese population. METHODS: A total of 3,177 Japanese subjects
aged 20-79 years were recruited in a cross-sectional clinical investigation
study. Habits of cigarette smoking were obtained at interviews by well-trained
staff. The diagnosis of metabolic syndrome was based on the new criterion in
Japan. RESULTS: Four hundred and forty men (35.3%) and 142 women (7.4%) were
current smokers. Three hundred thirty four men (26.8%) and 69 women (3.6%) were
diagnosed as metabolic syndrome. The prevalence of current smoker in subjects
with metabolic syndrome was significantly higher than in subjects with non
metabolic syndrome in men with and without adjustment for age. The prevalence of
metabolic syndrome in men with Brinkman index > or = 600 was significantly higher
than that in men with Brinkman index < 600. CONCLUSION: The present study
indicated that cigarette smoking may be an important modifiable factor in
Japanese men with metabolic syndrome.
PMID- 17043375
TI - Cholangiocarcinoma at the cystic duct discovered by lymph node metastases with
clear cell transformation.
AB - We encountered a case with cholangiocarcinoma of the cystic duct, which was first
manifested by multiple lymph node metastases with clear cell changes resembling
clear cell adenocarcinoma (CCC). Because the clear cell changes were not
prominent at the primary site, clear cell transformation might have occurred
preferentially at the metastatic lesion in this case. Alternatively, tumor cells
with clear cell transformation, found at the primary site, might have high
metastatic potential. The patient showed thromboembolism and hypercalcemia as
paraneoplastic syndromes at the terminal stage as reported in patients with CCC
of the ovary. Those complications might be common biological features of CCC.
PMID- 17043377
TI - Intractable desquamative interstitial pneumonia in a tattooed man.
AB - A 20-year-old man with a 15 pack-year history of cigarette smoking had a tattoo
outlined on his back with blue pigment. He noticed a dry cough and shortness of
breath on exertion when the pigment of other colors was added at the age of 27.
He visited our hospital two years later because of severe dyspnea. He was
diagnosed with desquamative interstitial pneumonia by surgical lung biopsy.
Steroid therapy with cessation of smoking was partially effective, however his
disease worsened again and he died three and a half years after the diagnosis
because of respiratory failure.
PMID- 17043376
TI - Acute cerebral infarction during combination chemotherapy with s-1 and cisplatin
for a young patient with a mucin-producing adenocarcinoma of the stomach.
AB - We report a 29-year-old woman with gastric cancer who developed Trousseau's
syndrome, a malignancy-related thromboembolism, during chemotherapy. She was
diagnosed with a mucin-producing adenocarcinoma of the stomach, and chemotherapy
with S-1 and cisplatin was commenced. During treatment, she developed a sudden
onset of right hemiplegia. Magnetic resonance imaging showed an acute cerebral
infarction of the left cerebral hemisphere. The underlying pathophysiology is
thought to be chronic disseminated intravascular coagulation due to mucin
producing adenocarcinomas. However, cisplatin-induced vascular toxicity and
hypercoagulability caused by decreased plasma protein C activity, elevated plasma
von-Willebrand factor levels, and hypomagnesemia has also been proposed to be
associated with thrombogenicity.
PMID- 17043378
TI - CD8-positive T cell-induced liver damage was found in a patient with
polymyositis.
AB - We describe a case of polymyositis (PM) with liver injury that occurred in a
patient with rheumatoid arthritis (RA). A 74-year-old woman who had a 12-year
history of RA was admitted to our hospital because of muscle weakness and liver
dysfunction. CD8-positive T cell infiltration was found in the interstitium of
both the liver and muscle. In addition to the administration of a large amount of
prednisolone (PSL), high-dose intravenous immunoglobulin (IVIG) successfully
improved myositis and hepatitis. Our case indicates the pathogenic potential of
CD8-positive T cells in PM-associated liver injury.
PMID- 17043379
TI - Antisynthetase syndrome associated with sarcoidosis.
AB - A 30-year-old man complained of polyarthralgia and fatigue. The clinical findings
and laboratory data included myositis, polyarthritis, interstitial pneumonia,
Raynaud's phenomenon, mechanic's hand, and anti PL-7 antibody (threonyl-tRNA
synthetase antibody). All of these signs were consistent with antisynthetase
syndrome. His chest radiograph revealed bilateral hilar lymphadenopathy. Biopsy
specimens from his mediastinal lymph node and muscle showed noncaseating
epithelioid cell granulomas. Lung histology revealed nonspecific interstitial
pneumonia. Antisynthetase syndrome associated with sarcoidosis was diagnosed.
Interstitial pneumonia in this patient responded well to high-dose corticosteroid
therapy.
PMID- 17043380
TI - Acute respiratory failure associated with miliary tuberculosis successfully
treated with sivelestat sodium hydrate.
PMID- 17043381
TI - Superior mesenteric artery syndrome.
PMID- 17043382
TI - Disseminated mucormycosis (zygomycosis) in acute myeloid leukemia.
PMID- 17043383
TI - An incidentally found case of multiple localized segmented painless dissections
of the descending aorta like gnarled tree.
PMID- 17043384
TI - Isolation and identification of F-spondin in the boar testis and its production
during testis growth.
AB - F-spondin/vascular smooth muscle cell growth-promoting factor (VSGP), purified
from the follicular fluid of adult bovine ovaries, has been identified as a
promoter of neuronal differentiation and vascular smooth muscle growth. The
objectives of the present study were (1) to clarify whether F-spondin is also
produced in the testis, which is ontogenically equivalent to the ovary, and (2)
to examine whether production of this protein changes with testicular growth. To
isolate F-spondin from the testis, testicular homogenates obtained from 8-week
old boars were sequentially subjected to heparin-Sepharose chromatography,
diethylaminoethyl (DEAE)-Sepharose chromatography, and reverse-phase high
performance liquid chromatography (RP-HPLC). The isolated protein had a molecular
mass of approximately 110 kDa and was cross-reactive with anti-F-spondin antibody
by Western blotting. The purified protein was further characterized by amino acid
sequence analysis of its internal peptide. The sequence obtained was GEQCNIVPDN
VD, and a homology search indicated that the purified protein is a homologue of
rat, human, and bovine F-spondin. By fractionation of the same amounts of testis
tissue obtained from 1-, 8-, 16-, and 40-week-old boars, we analyzed age-related
production of F-spondin in the testis. Western blotting of the fractions obtained
from RP-HPLC revealed the presence of a band at approximately 110 kDa,
corresponding to F-spondin, in the testes obtained from boars between 1 and 16
weeks old, but this band was not detected at 40 weeks. These results clearly
indicate that (1) the porcine testis produces F-spondin and that (2) production
of this protein is evident in the immature porcine testis, but not the adult
testis.
PMID- 17043385
TI - Differential effect of follicle-stimulating hormone and estradiol on expressions
of vascular endothelial growth factor (VEGF) 120, VEGF164 and their receptors in
bovine granulosa cells.
AB - Vascular endothelial growth factor (VEGF) isoforms (VEGF 120 and VEGF 164)
secreted by granulosa cells are involved in thecal angiogenesis during follicular
development in the bovine ovary. However, whether the transcript of the VEGF120
and VEGF164 isoforms differs during follicular development in the ovary is still
unknown. We first examined the gene expression of VEGF120, VEGF164, fms-like
tyrosine kinase (Flt-1), and fetal liver kinase (Flk-1) in the granulosa cells
(GCs) and theca cells (TCs) of pre-selection and post-selection follicles (PRF
and POF respectively) from the bovine ovary. Then we examined the effects of FSH
and estradiol (E2) on these factors in cultured bovine GCs. Messenger RNA (mRNA)
expression was quantified using real-time PCR methods. The concentrations of E2
and P4 in the follicular fluid (FF) of the PRF and POF were estimated using an
enzyme immunoassay (EIA). The concentrations of E2 and P4 in the FF were
significantly higher in the POF than in the PRF. The ratio of E2/P4 in PRF and
POF was 0.37 and 3.8, respectively. The expression levels of the VEGF120,
VEGF164, and Flk-1 mRNAs in the GCs of POF with high E2 concentration were higher
than those of PRF. The levels of the Flt-1 and Flk-1 mRNAs in the TCs were not
different between PRF and POF. Since E2 in the FF of the POF used in the present
study was high compared with the PRF, we examined the effects of E2 and FSH on
the expression of the above genes using cultured GCs. Expression of VEGF120 mRNA
was induced by a low concentration (1 ng/ml) of E2, whereas the levels of VEGF164
and Flk-1 mRNAs were not affected by E2. FSH stimulated the expression of the
VEGF isoforms and Flk-1 genes. Moreover, the expression of those genes was
enhanced when low E2 (1 ng/ml) was added to FSH. In conclusion, our data
indicates that the VEGF isoforms have a follicle stage-dependent expression
pattern. Thus, our results suggest that the expression of VEGF isoforms may be
associated with characterization of the preovulatory phenotype during follicle
development in the bovine ovary.
PMID- 17043387
TI - Excretion patterns of fecal progestagens, androgen and estrogens during
pregnancy, parturition and postpartum in okapi (Okapia johnstoni).
AB - The aim of the present study was to establish a simple method to monitor ovarian
activity and non-invasively diagnose pregnancy in okapi (Okapia johnstoni). The
feces of a female okapi were collected daily or every 3 days for 28 months.
Steroids in lyophilized feces were extracted with 80% methanol, and the fecal
levels of immunoreactive progestagens (progesterone and pregnanediol
glucuronide), androgen (testosterone), and estrogens (estradiol-17beta and
estrone) were determined by enzyme immunoassays with commercially available
antisera. Using the progesterone profiles, the durations of the luteal phase,
follicular phase, and estrous cycle were determined to be 11.1 +/- 0.4, 5.3 +/-
0.6, and 16.5 +/- 0.7 days (n=22), respectively. Fecal levels of immunoreactive
progesterone, pregnanediol glucuronide, and testosterone gradually increased from
early pregnancy and peaked several months before parturition. More pregnanediol
glucuronide was excreted in feces than progesterone during late pregnancy, but
not during the estrous cycle. Although the fecal concentrations of immunoreactive
estradiol-17beta and estrone change a little throughout pregnancy and non
pregnancy, they rose sharply and temporarily on the day following parturition.
The present study indicates that fecal assays with commercial antisera for
progesterone and pregnanediol glucuronide are useful for evaluating luteal
activity and diagnosing pregnancy and indicates that estrogens might have some
role as a trigger of parturition.
PMID- 17043386
TI - Metabolic profiles in ovulatory and anovulatory primiparous dairy cows during the
first follicular wave postpartum.
AB - Metabolic hormones affect ovarian function in the cow. However, the relationship
between metabolic factors and ovarian function is not clear in the postpartum
primiparous cow because they are still growing. The aim of the present study was
to investigate in detail the time-dependent profile of the metabolic hormones,
metabolites, and milk yields of ovulatory and anovulatory primiparous cows during
the first follicular wave postpartum. We used 16 primiparous Holstein cows and
obtained blood samples for the profiles of metabolites (glucose; non-esterified
fatty acid, NEFA; ketone body; total cholesterol; and aspartate
aminotransferase), metabolic hormones (growth hormone, GH; insulin-like growth
factor-I, IGF-1; and insulin), and progesterone every other day from 1 to 21 days
postpartum. In addition, all ovaries were observed using ultrasound. Dairy milk
yield was recorded during the experimental period. In all cows, the first
follicular wave postpartum was observed and 6 of the cows ovulated. The plasma
glucose (P<0.0001) and IGF-1 (P<0.001) concentrations were lower and the plasma
NEFA (P<0.0001) and ketone bodies (P<0.0001) concentrations and daily milk yield
(P<0.0001) were higher in the anovulatory cows compared to the ovulatory cows.
However, the GH levels, which enhance lipolysis for milk production, insulin and
other metabolites did not differ between the two groups. In conclusion, the
present study suggests that anovulation of the dominant follicle during the first
follicular wave postpartum in primiparous cows is induced by low IGF-1 levels
that are similar to those of multiparous cows. In addition, anovulatory cows are
likely to mobilize body fat stores for milk production more easily than ovulatory
cows.
PMID- 17043388
TI - Effects of exogenous estradiol and progesterone on plasma concentrations of
leptin in ewes in non-breeding season.
AB - Estradiol and progesterone may play a role in controlling leptin secretion by
utilizing their receptors in adipocytes and the genomic mechanisms of the leptin
gene. This study was conducted to evaluate the effects of exogenous sex steroids
on the blood leptin concentrations in ewes in the non-breeding season.
Multiparous ewes were fed to maintenance level for their live weights. Blood
samples were collected at 12-h intervals from Days -3 to -1 to determine the
basal leptin levels (pre-injection period). From Day 0 to Day 5 (injection
period), blood sampling continued at 12-h intervals, and the ewes were injected
intramuscularly at 24-h intervals with oil, 50 mg progesterone in oil, 1 mg of
estradiol in oil, or both steroids in oil. Leptin was measured using a sensitive
and specific radioimmunoassay based on recombinant bovine leptin. Overall, plasma
concentrations of leptin were not affected by any of the steroid treatments, and
there were no differences in the value of leptin between the pre-injection and
injection periods among the 4 groups. Therefore, the exogenous estrogen and
progesterone used in this study do not have a strong effect on the blood leptin
concentrations of ewes in the non-breeding season.
PMID- 17043389
TI - Absence of radioadaptive responses in four cell-lines in vitro as determined by
colony formation assay.
AB - The purpose of this study was to investigate radioadaptive response in 4 cell
lines under identical conditions using a colony assay. First, 4 cell-lines (V79,
HeLa S3, EMT6 and SCCVII) were exposed to 8 Gy at various intervals after
pretreatment with an adapting dose of 50 mGy or without it. Second, V79 cells
were exposed to 8 Gy at 4.5 hrs after an adapting dose of 0 to 400 mGy. Third,
V79 cells were exposed to 2, 4 or 6 Gy at 6 hrs after an adapting dose of 0 or 50
mGy. In the last experiment, an adapting dose was given either immediately after
cell plating or 24 hrs later. Cell survival was assessed by a standard colony
assay. Adaptive response was not observed in any of the 4 lines tested. In V79
cells, no adaptive response was seen even by changing the adapting dose,
challenging dose, and timing of adapting radiation after cell plating. Although
radioadaptive response has been reported for the V79 cell-line, we could not
reproduce the result. We also failed to demonstrate the phenomenon in the other 3
tumor cell-lines in culture.
PMID- 17043390
TI - Double-door laminoplasty using autologous spinous process for the management of
cervical myelopathy.
AB - We describe a technique of double-door laminoplasty for the management of
cervical myelopathy using the autologous spinous process instead of an artificial
spacer. The aims in the present study were to determine the fusion rate and the
incidence rate of breakage in the autologous spinous process, and to assess its
efficacy for cervical laminoplasty. Twenty-three patients of cervical myelopathy
were treated with double-door laminoplasty followed by implantation of the
autologous spinous process. The spinous process from C3 to C7 was resected, at 8
mm from the basal part of the spinous process. The autologous spinous process was
made from the removed spinous process, and was implanted between each expanded
laminae. Post-operative CT scanning determined the fusion rate between the
expanded laminae and the autologous spinous process as 70.4% at 3 months, and
93.5% at 6 months, after the operation. There was no dissociation and no breakage
in the autologous spinous process during the follow-up observation period. There
were certain advantages to our technique including the high fusion rate and good
stability in the autologous spinous process. In addition, this technique was less
expensive than other techniques using an artificial spacer. These findings
indicated that this technique was a reliable procedure for effectively treating
of cervical myelopathy which are caused by multisegmental cervical canal
stenosis.
PMID- 17043391
TI - Effects of systemic deep hypothermia and subarachnoid block on the longitudinally
conducting evoked spinal cord potentials in man.
AB - The present study reports the effects of systemic deep hypothermia (SDH) and
subarachnoid block (SAB) on the longitudinally conducting evoked spinal cord
potential (conducting ESCP) in man. Before induction of anesthesia, a pair of
bipolar catheter electrodes was introduced to the epidural space: one at the
level of the cervical enlargement and the other at the lumbosacral enlargement.
The conducting ESCP was produced by electrical stimulation through the upper
electrode and recorded through the lower electrode, and vice versa. SDH Study:
Subjects were 6 patients who underwent replacement surgery of an aortic aneurysm
with deep hypothermia anesthesia. The peak latency of the ESCP was gradually
prolonged and the duration was widened with cooling via extracorporeal
circulation. The amplitude of ESCP showed a biphasic change over the course of
cooling with a turning point of around 30 degrees C in esophageal temperature.
The ESCP was well observed until blood temperatures as low as near 10 degrees C.
The result shows that ESCP is available as an intra-operative monitoring
parameter of the spinal function even under SDH. SAB Study: Subjects were 7
patients, 6 of whom had SAB and the remaining 1 intravenous application of a
local anesthetic. The conducting ESCP was markedly depressed or disappeared
completely even after SAB with clinical doses of various local anesthetics, while
it was hardly affected by the intravenous application. The result implies that
SAB causes, at least partially, the conduction block within the spinal cord.
PMID- 17043392
TI - Comparison of preoperative fine-needle aspiration cytology diagnosis and
histopathological diagnosis of salivary gland tumors.
AB - We investigated 115 patients with salivary gland epithelial tumors who had
undergone preoperative fine needle aspiration cytology (FNAC) of salivary glands
and had been diagnosed by postoperative histopathological examination. We
compared the findings of preoperative FNAC with their histopathological types in
salivary gland tumors, and discuss the results and problems. The diagnostic
accuracy, sensitivity, and specificity of preoperative FNAC of salivary glands
were 98.2%, 88.2%, and 100%, respectively. The percentage of inadequate specimens
was 6.1%. The rates of agreement in the diagnosis of pleomorphic adenoma, Warthin
tumor, and basal cell adenoma were 96%, 92.9%, and 55.5%, respectively. The rate
of agreement of histopathological types in the malignant tumors was 30%. We
realized again not only that the diagnostic accuracy of preoperative FNAC for
salivary gland tumors was high, but also that it was a safe, easy-to-perform,
clinically very useful diagnostic procedure. However, this study exposed several
problems which are the inadequate sampling rate and the difficulty in diagnosing
malignant tumors. We have been making efforts to take appropriate specimens by
writing comments on the cytological report indicating a re-examination, or by the
presence of the clinical laboratory technician at the FNAC procedure. We consider
it necessary to adequately re-aspirate the solid portion after cyst fluid
aspiration, or to re-perform FNAC at a later date, and to improve the diagnostic
accuracy by further experience with more patients.
PMID- 17043393
TI - Effects of endurance training on blood lipid profiles in adolescent female
distance runners.
AB - The purpose of this study was to investigate the cross-sectional and longitudinal
effects of endurance training on the relationships of body composition, blood
lipid profiles and sex hormones in adolescent female distance-runners. We cross
sectionally compared body composition, blood lipid profiles and blood sex
hormones of non-athletes (n=7) and distance-runners (n=8), with the similar lower
level of BMI (17.1 kg/m(2) vs. 18.7 kg/m(2), respectively). After the cross
sectional comparison on the influence of endurance training, body composition,
blood lipid profiles and blood sex hormones were examined at pre- and post-one
year endurance training in the distance-runners (n=6) to determine longitudinal
effects. %Fat in distance-runners revealed a tendency to be lower than that in
non-athletes (23.8+/-3.5 vs 27.3+/-2.5%). Both groups showed good blood lipid
profiles, such as high levels of high density lipoprotein-cholesterol (HDL-c),
HDL-2c, and apolipoprotein A-I (ApoA-I). However, the estrogen (E(2)) level of
distance-runners was less than one third of that in non-athletes (30.5+/-11.3 vs
112.9+/-66.2 pg/ml, p<0.01). In addition, the blood E(2) levels (pg/ml) were
significantly associated with the internal fat mass (IF, kg) in all subjects (r=
0.613, p<0.05, n=15). On the other hand, the overall body composition and good
blood lipid profiles in the longitudinal comparison were maintained to a constant
level for one year endurance training, except for significant elevations in the
two enzyme activities and E(2) level (LPL activity: from 145.3+/-40.8 to 362.2+/
65.8 ng/ml, HTGL activity: from 0.054+/-0.020 to 0.173+/-0.080 micromole/ml/min,
E(2): from 30.7+/-13.2 to 65.6+/-24.2 pg/ml, p<0.05). These results suggest that
the lipid profiles such as HDL-c and Apo A-I in adolescent female distance
runners could be rather affected by endurance training, despite the low level of
E(2) for a long term.
PMID- 17043394
TI - Significance of the " beak sign"in the differential diagnosis of uterine
lipoleiomyoma from ovarian dermoid cyst.
AB - A case of uterine lipoleiomyoma in a 72-year-old woman is presented. Although a
series of imaging studies suggested a lipomatous tumor, diagnosis was difficult
because the tumor appeared as a pedunculated mass extending from the uterine
body. To distinguish the tumor from an ovarian lipomatous tumor, the "beak sign"
in a magnetic resonance imaging study was diagnostic in this case. The purpose of
this paper is to review lipomatous masses of the female pelvis, to discuss the
differential diagnosis of the unusual imaging features, and to discuss imaging
techniques to optimize pelvic mass characterization.
PMID- 17043395
TI - Appearance-specific satiety increases appetite and quality of life in patients
with metastatic liver tumor: a case report.
AB - Loss of appetite is frequently seen and is a main factor affecting quality of
life (QOL) in patients with advanced cancer. The etiology for loss of appetite in
patients with cancer is multifactorial. The sensory properties of food are
factors regulating appetite. Changes in taste, smell and texture of foods
influence food intake. The appearance of the food is also a notable factor in
sensory-specific satiety. We described a 46-year-old Japanese woman with multiple
metastatic liver tumors. Although there was no obvious factor for loss of
appetite, she suffered from a loss of appetite and subsequent malnutrition. In
order to improve the appearance of food, we reduced the diet to 1,000 kcal/day
from 1,500 kcal/day. On the new diet, the patient's appetite significantly
increased and patient's nutritional status was improved. Eating whole diet was an
important achievement and increased in mental aspects of QOL. Arrangement for the
appearance of food may be a simple and nontoxic therapeutic strategy for patients
with cancer suffering a loss of appetite.
PMID- 17043396
TI - Comparative phylogeography of three Leptocarabus ground beetle species in South
Korea, based on the mitochondrial COI and nuclear 28S rRNA genes.
AB - We analyzed the intraspecific gene genealogies of three Leptocarabus ground
beetle species (L. seishinensis, L. semiopacus, L. koreanus) in South Korea using
sequence data from the mitochondrial cytochrome oxidase subunit I (COI) and
nuclear 28S rRNA (28S) genes, and compared phylogeographical patterns among the
species. The COI data detected significant genetic differentiation among local
populations of all three species, whereas the 28S data showed genetic
differentiation only for L. seishinensis. The clearest differentiation of L.
seishinensis among local populations was between the northern and southern
regions in the COI clades, whereas the 28S clade, which likely indicates
relatively ancient events, revealed a range expansion across the northern and
southern regions. Leptocarabus semiopacus had the most shallow differentiation of
the COI haplotypes, and some clades occurred across the northern and southern
regions. In L. koreanus, four diverged COI clades occurred in different regions,
with partial overlaps. We discuss the difference in phylogeographical patterns
among these Leptocarabus species, as well as between these and other groups of
carabid beetles in South Korea.
PMID- 17043397
TI - High levels of morphological variation despite close genetic relatedness between
Zoanthus aff. vietnamensis and Zoanthus kuroshio (Anthozoa: Hexacorallia).
AB - Recent investigations into the encrusting anemone genus Zoanthus using molecular
and morphological techniques have begun to bring order to this taxonomically
neglected group. Previous studies have confirmed the existence of three distinct
species present in southern Japan: Z. sansibaricus, Z. kuroshio, and Z. gigantus.
Results from such studies show species of Zoanthus to be highly morphologically
plastic, often incorporating morphotypes with varying oral disk color and oral
disk diameter. Literature lists the species Z. aff. vietnamensis as occurring in
southern Japan and throughout the western Pacific Ocean, but due to the
morphological plasticity of Zoanthus species, a re-examination of Z. aff.
vietnamensis using molecular techniques was needed. Here, using mitochondrial 16S
rDNA and the nuclear internal transcribed spacer of ribosomal DNA (ITS-rDNA)
sequences, as well as morphological data, we have examined several nominal Z.
aff. vietnamensis samples collected from Kagoshima Bay and Yakushima Island,
Japan. Based on polyp length and diameter, oral disk diameter, mesentery and
tentacle numbers, and colony form, Z. aff. vietnamensis is easily distinguishable
from Z. sansibaricus, Z. kuroshio, and Z. gigantus. However, despite these clear
morphological differences, our mitochondrial and nuclear sequence-based
phylogenies indicate that Z. aff. vietnamensis and Z. kuroshio are very closely
related (perhaps conspecific), highlighting the morphological plasticity of this
genus and the difficulty of species identification based on morphological data
alone.
PMID- 17043398
TI - Round-trip catadromous migration in a Japanese amphipod, Sternomoera rhyaca
(Gammaridea: Eusiridae).
AB - We conducted a field study of the life cycle of the eusirid gammaridean amphipod
Sternomoera rhyaca Kuribayashi, Mawatari, and Ishimaru, 1996 in a stream at
Gokibiru, Hokkaido, Japan over the course of two non-consecutive years. This
species is biennial; it spends most of its life in freshwater, but undertakes a
short catadromous migration to the sea for reproduction. Reproduction occurs from
March-June. Mature adults drift downstream to the sea singly and in precopulating
pairs. Copulation and oviposition in the marsupium occur in mixed water at the
stream mouth. Males die after copulation; ovigerous females return upstream by
walking or swimming, where their eggs develop and hatch, after which the females
also die. Juveniles remain in the stream, growing until they reach sexual
maturity. Laboratory experiments showed that survivorship of all stages was
lowest in seawater and highest in freshwater, though juveniles survived equally
well in mixed water (50% seawater) and freshwater. Eggs developed to hatching
only in freshwater; hatchlings in seawater and mixed water died within one and 21
days, respectively. Thus, S. rhyaca is well adapted to freshwater. Indeed, the
only stages that required elevated salinity were copulation and subsequent
oviposition, and we speculate that freshwater inhibits the female pre
reproductive molt. Because the life cycle of S. rhyaca has the most
ontogenetically and temporally restricted saltwater phase known in any
catadromous animal, its origin and maintenance are of evolutionary interest. We
discuss two alternative hypotheses for the origin of the migratory life cycle,
and discuss its maintenance in terms of fitness costs and benefits.
PMID- 17043399
TI - Experience-based agonistic behavior in female crickets, Gryllus bimaculatus.
AB - Fighting behavior in male crickets is already well described, and some of the
mechanisms underlying aggression and aggressive motivation have already been
revealed. Much less is known about female/female interactions. Here, we report
that adult female crickets that had been isolated for several days readily
entered into agonistic interactions with conspecific individuals. Characteristic
dyadic encounters between isolated females escalated in a stepwise manner and
were concluded with the establishment of a dominant/subordinate relationship. For
15 to 30 minutes following an initial fight, former subordinate females showed a
dramatic change in agonistic behavior. If they were paired with the former
dominant opponent during this interval, a significant majority did not enter into
any aggressive interaction but instead actively avoided the opponent. A similar
experience-based and time-dependent increase in avoidance was observed when
former subordinate females were paired with unfamiliar naive opponents. However,
when faced with an unfamiliar subordinate individual in the second encounter, no
such increase in avoidance behavior was observed. We propose that the observed
changes in the behavior of former subordinate females are the consequence of a
change in the general state of arousal and of the recognition of dominance
status, but not of individual recognition. The fact that former dominant
individuals did not show similar experience-based changes in agonistic behavior
suggests that dominant/subordinate relationships between pairs of female crickets
are maintained mainly by the behavior of subordinate individuals.
PMID- 17043400
TI - Identification of a nuclear localization signal in mouse polycomb protein, M33.
AB - The mouse Polycomb group (PcG) protein M33 forms nuclear complexes with the
products of other PcG members and maintains repressed states of developmentally
important genes, including homeotic genes. In this context, nuclear localization
is a prerequisite for M33 to exert its function. However, we previously found
that M33 in mouse liver shuttles dynamically between the nucleus and the
cytoplasm, depending on the proliferative states of cells, coupled with
phosphorylation and dephosphorylation of M33 protein. To understand the mechanism
and significance of this phenomenon, we identified the functional nuclear
localization signal (NLS) of M33 protein. Deletion mutants that lack a particular
one of three putative NLS motifs failed to localize in the nucleus. Green
fluorescent protein (GFP) fused to this motif specifically localized in the
nucleus. We conclude that this amino-acid stretch in M33 acts as the functional
NLS for this protein.
PMID- 17043401
TI - Ultrastructure of the dermal chromatophores in a lizard (Scincidae: Plestiodon
latiscutatus) with conspicuous body and tail coloration.
AB - Microscopic observation of the skin of Plestiodon lizards, which have body
stripes and blue tail coloration, identified epidermal melanophores and three
types of dermal chromatophores: xanthophores, iridophores, and melanophores.
There was a vertical combination of these pigment cells, with xanthophores in the
uppermost layer, iridophores in the intermediate layer, and melanophores in the
basal layer, which varied according to the skin coloration. Skin with yellowish
white or brown coloration had an identical vertical order of xanthophores,
iridophores, and melanophores, but yellowish-white skin had a thicker layer of
iridophores and a thinner layer of melanophores than did brown skin. The
thickness of the iridophore layer was proportional to the number of reflecting
platelets within each iridophore. Skin showing green coloration also had three
layers of dermal chromatophores, but the vertical order of xanthophores and
iridophores was frequently reversed. Skin showing blue color had iridophores
above the melanophores. In addition, the thickness of reflecting platelets in the
blue tail was less than in yellowish-white or brown areas of the body. Skin with
black coloration had only melanophores.
PMID- 17043402
TI - Distribution and characterization of keratins in the epidermis of the tuatara
(Sphenodon punctatus; Lepidosauria, Reptilia).
AB - Reptilian scales are mainly composed of alpha-and beta-keratins. Epidermis and
molts from adult individuals of an ancient reptilian species, the tuatara
(Sphenodon punctatus), were analysed by immunocytochemistry, mono- and bi
dimensional electrophoresis, and western blotting for alpha- and beta-keratins.
The epidermis of this reptilian species with primitive anatomical traits should
represent one of the more ancient amniotic epidermises available. Soft keratins
(AE1- and AE3-positive) of 40-63 kDa and with isoelectric points (pI) at 4.0-6.8
were found in molts. The AE3 antibody was diffusely localised over the
tonofilaments of keratinocytes. The lack of basic cytokeratins may be due to
keratin alteration in molts, following corneification or enzymatic degradation of
keratins. Hard (beta-) keratins of 16-18 kDa and pI at 6.8, 8.0, and 9.2 were
identified using a beta-1 antibody produced against chick scale beta-keratin. The
antibody also labeled filaments of beta-cells and of the mature, compact beta
layer. We have shown that beta-keratins in the tuatara resemble those of lizards
and snakes, and that they are mainly basic proteins. These proteins replace
cytokeratins in the pre-corneoum beta-layers, from which a hard, mechanically
resistant corneoum layer is formed over scales. Beta-keratins may have both a
fibrous and a matrix role in forming the hard texture of corneoum scales in this
ancient species, as well as in more recently evolved reptiles.
PMID- 17043403
TI - First application of X-ray refraction-based computed tomography to a biomedical
object.
AB - We have developed X-ray refraction-based computed tomography (CT) that is able to
visualize soft tissue in between hard tissue. The experimental system consists of
Si(220) diffraction double-crystals and is called the DEI (diffraction-enhanced
imaging) method, in which the object is located between the crystals and a CCD
camera to acquire data as 360 X-ray images. The X-ray energy used was 17.5 keV.
The algorithm used to reconstruct CT images was developed by A. Maksimenko and
colleagues. We successfully visualized articular cartilage and the distribution
of bone marrow, which are inner structures. Our method has much higher contrast
compared to the conventional absorption-based CT system.
PMID- 17043404
TI - Light-sensitive motile iridophores and visual pigments in the neon tetra,
Paracheirodon innesi.
AB - Although motile iridophores in the longitudinal stripes of neon tetra skin are
under control of the sympathetic nervous system, they also respond to light
directly and show circadian color changes. Using neon tetra skin, we found that
the photoresponse of iridophores depends on light intensity, and that light near
500 nm is most effective. RT-PCR demonstrated the expression of mRNAs encoding
rhodopsin and two kinds of cone opsins (Pi-green1 and Pi-green2) in neon tetra
skin where the light-sensitive iridophores exist. These mRNAs are also expressed
in the lateral eyes. The cone opsin genes, Pi-green1 and Pi-green2, show high
similarity with the g101 and g103 genes of unique green cone opsins (belonging to
the MWS/LWS group) of the blind Mexican cavefish. These results show that Pi
green1, Pi-green2, and/or rhodopsin may play important roles in the photoresponse
of neon tetra iridophores, which are most sensitive to light near 500 nm.
PMID- 17043405
TI - Three new species of Leptolalax from Thailand (Amphibia, Anura, Megophryidae).
AB - Three new megophryid species, Leptolalax melanoleucus, L. fuliginosus, and L.
solus, are described from southwestern and southern Thailand on the bases of
acoustic and morphological characteristics. Leptolalax melanoleucus and L.
fuliginosus are similar to L. pelodytoides from northern Thailand, but differ
from it completely in advertisement call characteristics and ventral color.
Leptolalax solus is similar to L. heteropus from peninsular Malaysia, but differs
from it by advertisement call, as well as by some body proportions. The
distributional pattern of Leptolalax within Thailand is discussed.
PMID- 17043406
TI - Biomedical issues of dietary fiber beta-glucan.
AB - Beta-glucan is a polysaccharide in the form of fiber and the main element of
fiber in grains such as barley, oats, yeast and mushrooms. Many studies have
examined the efficacy of beta-glucan in terms of the lipid lowering effects,
blood sugar reduction, weight reduction, immune modulator, and anticarcinogenic
effect. However, there is no comprehensive review article on the biomedical
issues regarding beta-glucan. The authors searched for systematic reviews and
clinical experiments for each relevant topic and reviewed the biomedical effects
of beta-glucan, for the purpose of developing research strategies for the future.
PMID- 17043407
TI - X-linked Opitz G/BBB syndrome: identification of a novel mutation and prenatal
diagnosis in a Korean family.
AB - X-linked Opitz G/BBB syndrome (XLOS; MIM 300000) is a rare multiple congenital
anomaly disorder that is characterized by facial anomalies,
laryngeal/tracheal/esophageal defects and genitourinary abnormalities. XLOS is
caused by mutations in the MID1 gene which encodes a microtubule-associated RING
Bbox-Coiled-coil (RBCC) protein. We recently found a four-year Korean male
patient who was suspected of having XLOS. Mutation analysis of the MID1 gene in
the patient and his mother demonstrated that the patient had a novel insertion
mutation (c.1798_1799-insC), and his mother was a heterozygous carrier of the
mutation. After identification of the causative mutation in this family, prenatal
diagnosis of two consecutive fetuses were successfully undertaken. This is the
first report on a genetically confirmed case of XLOS in Korea.
PMID- 17043408
TI - Identification of a novel single nucleotide polymorphism of HADHA gene at a
referred primer-binding site during pre-diagnostic tests for preimplantation
genetic diagnosis.
AB - The pre-diagnostic test for preimplantation genetic diagnosis (PGD) of long-chain
3-hydroxyacyl-CoA dehydrogenase deficiency was performed by polymerase chain
reaction (PCR) and direct sequencing for hydroxyacyl-Coenzyme A dehydrogenase/3
ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (HADHA) gene. We obtained
unexpected genotyping results of HADHA gene by allele drop-out in the analysis of
patients' genomic DNA samples with a referred PCR primer set. Upon further
analysis with a re-designed primer set, we found a novel single nucleotide
polymorphism (SNP) at the referred primer-binding site in the normal allele of
HADHA gene (NT_022184, 5233296 a>t). We found that the frequency of this novel
SNP was 0.064 in Korean population. Pre-diagnostic test using single lymphocytes
and clinical PGD were successfully performed with the re-designed primer set.
Nineteen embryos (95.0%) among 20 were successfully diagnosed to 5 homozygous
mutated, 8 heterozygous carrier and 6 wild type. Among 6 normal embryos, well
developed and selected 4 embryos were transferred into the mother's uterus, but a
pregnancy was not achieved. We proposed that an unknown SNP at primer-binding
sites would be a major cause of allele drop-out in the PGD for single gene dis
order.
PMID- 17043409
TI - A Korean female patient with thiamine-responsive pyruvate dehydrogenase complex
deficiency due to a novel point mutation (Y161C)in the PDHA1 gene.
AB - Pyruvate dehydrogenase complex (PDHC) deficiency is mostly due to mutations in
the X-linked E1alpha subunit gene (PDHA1). Some of the patients with PDHC
deficiency showed clinical improvements with thiamine treatment. We report the
results of biochemical and molecular analysis in a female patient with lactic
acidemia. The PDHC activity was assayed at different concentrations of thiamine
pyrophosphate (TPP). The PDHC activity showed null activity at low TPP
concentration (1 x 10(-3) mM), but significantly increased at a high TPP
concentration (1 mM). Sequencing analysis of PDHA1 gene of the patient revealed a
substitution of cysteine for tyrosine at position 161 (Y161C). Thiamine treatment
resulted in reduction of the patient's serum lactate concentration and dramatic
clinical improvement. Biochemical, molecular, and clinical data suggest that this
patient has a thiamine-responsive PDHC deficiency due to a novel mutation, Y161C.
Therefore, to detect the thiamine responsiveness it is necessary to measure
activities of PDHC not only at high but also at low concentration of TPP.
PMID- 17043410
TI - Changes of serum cytokines after the long term immunotherapy with Japanese hop
pollen extracts.
AB - Japanese hop (Hop J) pollen has been considered as one of the major causative
pollen allergens in the autumn season. We developed a new Hop J immunotherapy
extract in collaboration with Allergopharma (Reinbeck, Germany) and investigated
immunologic mechanisms during 3 yr immunotherapy. Twenty patients (13 asthma with
rhinitis and 7 hay fever) were enrolled from Ajou University Hospital. Sera were
collected before, 1 yr, and 3 yr after the immunotherapy. Changes of serum
specific IgE, IgG1, and IgG4 levels to Hop J pollen extracts and serum IL-10, IL
12, TGF-beta1 and soluble CD23 levels were monitored by ELISA. Skin reactivity
and airway hyper-responsiveness to methacholine were improved during the study
period. Specific IgG1 increased at 1 yr then decreased again at 3 yr, and
specific IgG4 levels increased progressively (p<0.05, respectively), whereas
total and specific IgE levels showed variable responses with no statistical
significance. IL-10, TGF-beta1 and soluble CD23 level began to decrease during
first year and then further decreased during next two years with statistical
significances. (p<0.05, respectively). In conclusion, these findings suggested
the favorable effect of long term immunotherapy with Hop J pollen extracts can be
explained by lowered IgE affinity and generation of specific IgG4, which may be
mediated by IL-10 and TGF-beta1.
PMID- 17043411
TI - Body mass index and C-reactive protein in the healthy Korean aged men.
AB - The purpose of this study was to determine the relationship between plasma C
reactive protein (CRP) and body mass index (BMI) in elderly Korean men. A review
of routine health examination records were done. Out of 671 eligible elderly men,
who had their routine health examination in 2001 at a Health Promotion Center of
a university hospital, 367 subjects were included after excluding inflammatory
conditions. Subgroup analyses were performed on those who did not smoke and
exercised regularly. Body composition, blood pressure, blood samples and
radiologic examinations including chest radiography and abdominal ultrasound were
obtained from each subject. Age, BMI, current smoking, regular exercise, WBC
count, HDL-cholesterol, gamma glutamyl transferase were independently associated
with logCRP. BMI subgroups according to the Asia-Pacific guideline did not show
any difference in CRP level from each other by ANCOVA (p>0.05). However, BMI
groups subdivided according to our criteria showed an association with CRP; the
CRP level was lowest in the group of BMI between 18.5-19.4 and showed significant
difference from BMI group of the highest BMI group (>or=29.0). Since elevated CRP
levels are associated with higher risk for cardiovascular disease, lower BMI
(18.5-19.4) levels may be advised for healthy elderly men in Korea.
PMID- 17043412
TI - Community-acquired versus nosocomial Klebsiella pneumoniae bacteremia: clinical
features, treatment outcomes, and clinical implication of antimicrobial
resistance.
AB - We conducted this study to compare clinical features, outcomes, and clinical
implication of antimicrobial resistance in Klebsiella pneumoniae bacteremia
acquired as community vs. nosocomial infection. A total of 377 patients with K.
pneumoniae bacteremia (191 community-acquired and 186 nosocomial) were
retrospectively analyzed. Neoplastic diseases (hematologic malignancy and solid
tumor, 56%) were the most commonly associated conditions in patients with
nosocomial bacteremia, whereas chronic liver disease (35%) and diabetes mellitus
(20%) were the most commonly associated conditions in patients with community
acquired bacteremia. Bacteremic liver abscess occurred almost exclusively in
patients with community-acquired infection. The overall 30-day mortality was 24%
(91/377), and the mortality of nosocomial bacteremia was significantly higher
than that of community-acquired bacteremia (32% vs. 16%, p<0.001). Of all
community-acquired and nosocomial isolates, 4% and 33%, respectively, were
extended-spectrum cephalosporin (ESC)-resistant, and 4% and 21%, respectively,
were ciprofloxacin (CIP)-resistant. In nosocomial infections, prior uses of ESC
and CIP were found to be independent risk factors for ESC and CIP resistance,
respectively. Significant differences were identified between community-acquired
and nosocomial K. pneumoniae bacteremia, and the mortality of nosocomial
infections was more than twice than that of community-acquired infections.
Antimicrobial resistance was a widespread nosocomial problem and also identified
in community-acquired infections.
PMID- 17043413
TI - Seroprevalence of Coxiella burnetii infection in dairy cattle and non-symptomatic
people for routine health screening in Korea.
AB - We report results on the seroprevalence of antibodies to Coxiella burnetii in
cattle and healthy people in Korea. Upon agreement with dairy owners, serum
samples from 414 dairy cattle were collected between March and June 2001 and
samples from 205 people for health screening were collected between April and
December 2002. The sera were analyzed for the presence of anti-C. burnetii phase
II antibodies using an indirect microimmunofluorescence test; strong fluorescence
at a 1:32 dilution was regarded as positive. The overall seroprevalence of C.
burnetii in cattle in Korea was 25.6%, with regional variation from 8.9 to 59.3%.
Of the positive serum samples, 75.5% had antibody titers >or=1:256. By contrast,
only 1.5% of people in a rural area were seropositive, and most of the positive
samples had low antibody titers. In conclusion, this study showed that relatively
high seropositivity of C. burnetii in dairy cattle, accordingly, the studies on
the high-risk groups are needed to evaluate the seroprevalence for this organism
in Korea.
PMID- 17043414
TI - Molecular analysis of isoleucyl-tRNA synthetase mutations in clinical isolates of
methicillin-resistant Staphylococcus aureus with low-level mupirocin resistance.
AB - Emergence and spread of low-level mupirocin resistance in staphylococci have been
increasingly reported in recent years. The aim of this study was to characterize
missense mutations within the chromosomal isoleucyl-tRNA synthetase gene (ileS)
among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA)
with low-level mupirocin resistance. A total of 20 isolates of MRSA with low
level mupirocin resistance (minimal inhibitory concentration, 16-64 microg/mL)
were collected from 79 patients in intensive care units for six months. The
isolates were analyzed for isoleucyl-tRNA synthetase (IleS) mutations that might
affect the binding of mupirocin to the three-dimensional structure of the S.
aureus IleS enzyme. All isolates with low-level mupirocin resistance contained
the known V588F mutation affecting the Rossman fold, and some of them
additionally had previously unidentified mutations such as P187F, K226T, F227L,
Q612H, or V767D. Interestingly, Q612H was a novel mutation that was involved in
stabilizing the conformation of the catalytic loop containing the KMSKS motif. In
conclusion, this study confirms that molecular heterogeneity in ileS gene is
common among clinical MRSA isolates with low-level mupirocin resistance, and
further study on clinical mutants is needed to understand the structural basis of
low-level mupirocin resistance.
PMID- 17043415
TI - Clinical overview of extrapulmonary small cell carcinoma.
AB - The objective of this study was to review the natural history of extrapulmonary
small cell carcinoma (EPSCC) with specific emphasis on clinical features,
response to treatment and survival. The records of all patients (n=34) with EPSCC
treated at Yeungnam University Medical Center and Catholic University of Daegu
Medical Center between 1998 and 2005 were retrieved and reviewed. The primary
sites of tumor were the esophagus and thymus in 6 patients (17.6%) each, pancreas
and stomach in 5 patients each (14.7%); other sites included were the cervix,
abdominal lymph nodes, abdominal wall, bladder, colon, maxillary sinus, nasal
cavity, ovary, parotid gland and liver. Twenty three patients out of 34 had
limited disease. The median survival of all patients was 14 months. Independent
prognostic factors included stage and primary tumor location. The prognosis for
the patients with extensive disease and in the gastrointestinal group was
unfavorable. EPSCC is a non homogeneous disease entity. As a result of its
frequent recurrence, multimodal therapy has a better outcome even in cases of
limited disease. Combination chemotherapy plays a central role for treatment of
extensive disease in EPSCC. Further multicenter studies are now needed to
determine more details regarding disease sub-class and optimal treatment
modality.
PMID- 17043416
TI - Human metapneumovirus infection in hospitalized children with acute respiratory
disease in Korea.
AB - Human metapneumovirus (hMPV) is a recently isolated virus, mostly associated with
acute lower respiratory infection in children, of which symptoms are similar to
those of respiratory syncytial virus (RSV) infection. The aim of our study was to
determine the frequency of hMPV in hospitalized children with acute respiratory
tract disease in Korea. Nasal aspirates from hospitalized children with
respiratory infections under 15 yr old between December 2003 and February 2005
were included in the study. Each sample was analyzed for RSV, adenovirus,
influenza virus A and B, and parainfluenza virus by indirect fluorescent assay
(IFA). F-gene sequences were used for PCR for the detection and sequencing of
hMPV. In total 381 samples, negative samples in which any viral pathogen could
not be identified by IFA were 231 cases. hMPV was detected using reverse
transcriptase-PCR (RT-PCR) in 28 of 231 (12.1%) children who were not infected
with another respiratory viruses. The hMPV-infected children were diagnosed as
having pneumonia, bronchiolitis, bronchial asthma exacerbation, croup, and upper
respiratory tract infection. Most of the RT-PCR positive samples for hMPV were
collected in winter season. These results suggest that hMPV may be a responsible
pathogen causing acute respiratory tract infection in Korean children.
PMID- 17043417
TI - The stages of change in smoking cessation in a representative sample of Korean
adult smokers.
AB - This study reports the stages of change in smoking cessation in a representative
sample of Korean adult smokers. The study subjects, all adult smokers (n=2,422),
were recruited from the second Korea National Health and Nutrition Examination
Survey conducted in 2001. The stages of change were categorized using demographic
(age and sex), socioeconomic (education, residence, and household income), and
smoking characteristics (age at smoking onset, duration of smoking, and number of
cigarettes smoked per day). Age-stratified analyses of the association of
socioeconomic and smoking characteristics with the stages of change in male and
female smokers were also conducted. According to the stages of change, the study
population consisted of 37.6% (95% CI, 35.7-39.5) pre-contemplation, 56.0% (54.0
58.0) contemplation, and 6.4% (5.4-7.4) preparation. The associations between the
characteristics of the smokers and the stages of change were all statistically
significant. The age-stratified analyses showed that all the socioeconomic and
smoking characteristics were significantly associated with the stages in males,
while education and residence had significant associations in females. This study
revealed that a relatively small number of Korean smokers were prepared to quit
and the stage distribution might be influenced by demographic, socioeconomic, and
smoking characteristics.
PMID- 17043418
TI - Mid-term follow up of patients using the St. Jude Medical Aortic Connector System
for proximal vein graft in CABG.
AB - The aortic connector system may reduce stroke during proximal venous anastomosis.
However, the overall anastomotic patency rate has been generally reported to be
low. From October 2002 to March 2004, 68 patients who received proximal
anastomosis using the St. Jude Aortic Connector System were included in the
study. There were 47 men and 21 women and their mean age was 65.68+/-6.68 yr old
(52 to 85 yr). Grafts were evaluated by coronary angiography or multi-slice 16
channel 3-D CT at 6 days and at 6 months postoperatively. In the immediate
postoperative period, no stenosis was observed by either angiography (n=22) or 3D
CT (n=46). At 6-month postoperatively, we performed either angiography (n=7) or 3
D CT (n=52). Of these patients, 5 patients showed graft stenosis in the
midportion, and 3 in the ostium. There were no stroke. Simple, and effective
proximal anastomosis with good protection from cerebrovascular accident was
achieved especially when calcification or atheromatous plaque was observed at the
ascending aorta in the operation room. However, our mid term patency results
raise concerns related to venous graft stenosis in the midportion. Therefore,
longer follow up is recommended.
PMID- 17043419
TI - The effect of milrinone on the right ventricular function in patients with
reduced right ventricular function undergoing off-pump coronary artery bypass
graft surgery.
AB - This investigation evaluated the effect of continuous milrinone infusion on right
ventricular (RV) function during off-pump coronary artery bypass graft (OPCAB)
surgery in patients with reduced RV function. Fifty patients scheduled for OPCAB,
with thermodilution RV ejection fraction (RVEF) <35% after anesthesia induction,
were randomly allocated to either milrinone (0.5 microg/kg/min) or control
(saline) group. Hemodynamic variables and RV volumetric data measured by
thermodilution method were collected as follows: after anesthesia induction (T1);
10 min after heart displacement for obtuse marginal artery anastomosis (T2);
after pericardial closure (T3). Cardiac index and heart rate increased and
systemic vascular resistance significantly decreased in milrinone group at T2.
Initially lower RVEF of milrinone group was eventually comparable to control
group after milrinone infusion. RVEF did not significantly change at T2 and T3 in
both groups. RV end-diastolic volume in milrinone group consistently decreased
from the baseline at T2 and T3. Continuous infusion of milrinone without a bolus
demonstrated potentially beneficial effect on cardiac output and RV afterload in
patients with reduced RV function during OPCAB. However, aggressive augmentation
of intravascular volume seems to be necessary to maximize the effect of the
milrinone in these patients.
PMID- 17043420
TI - Transcatheter closure of fenestration with detachable coils after the Fontan
operation.
AB - We report our experience in 13 patients who underwent transcatheter closure of
Fontan fenestration with the Cook detachable coils. These patients underwent the
extracardiac type Fontan operation with a short conduit fenestration (n=7) or
lateral tunnel type with a punch-hole fenestration (n=6). Fenestration closure
was done at the mean age of 5.1+/-2.4 yr, average of 32 months after the Fontan
operation. We used one to three coils depending on the fenestration type, size,
and residual shunt. Aortic oxygen saturations increased by an average of 5.4 (2
9)% and mean pressures in the Fontan circuit increased by an average of 2.1 (0-6)
mmHg. During follow-up (median of 23 months), five patients (4 in extracardiac, 1
in lateral tunnel) had complete occlusion of the fenestration on
echocardiography. There was no immediate or late complication. Transcatheter
closure of fenestration in Fontan operation using the Cook detachable coil is a
safe and feasible technique. However, the coil was ineffective for closure of a
punch-hole fenestration in the lateral tunnel type operation. In the conduit type
fenestration, some modification of fenestration method instead of a short conduit
for coil closure or use of new device is necessary to increase complete closure
rate.
PMID- 17043421
TI - Sentinel lymph node radiolocalization with 99mTc filtered tin colloid in
clinically node-negative squamous cell carcinomas of the oral cavity.
AB - The objective of this study was to evaluate the feasibility of sentinel lymph
node biopsy by using a radiotracer lymphatic mapping technique in patients with
squamous cell carcinoma of the oral cavity, and the diagnostic value of this
technique. We studied twenty patients with previously untreated squamous cell
carcinomas of the oral cavity and N0 necks. After the peritumoral injection of
99mTc filtered tin colloid preoperatively, lymphoscintigraphy and intraoperative
mapping using a gamma detector were performed to localize sentinel nodes. An open
biopsy of the sentinel node was followed by complete neck dissection. We
identified the sentinel nodes in 19 of 20 patients (95.0%) by lymphoscintigraphy
and in all (100%) by intraoperative gamma detector. In all cases, the status of
the sentinel node accurately predicted the pathologic status of the neck with the
false negative rate being 0%. The negative predictive value for the absence of
cervical metastases was 100%. In conclusion, our radiolocalization technique of
sentinel nodes using 99mTc filtered tin colloid in N0 squamous cell carcinomas of
the oral cavity is technically feasible and appears to accurately predict the
presence of the occult metastatic disease.
PMID- 17043422
TI - Expression of cyclooxygenase-2, p53 and Ki-67 in gastric cancer.
AB - It has been reported that p53 mutation may contribute to upregulate
cyclooxygenase (COX)-2 expression that is observed in malignant tissues. These
molecules are involved in carcinogenesis by affecting tumor cell proliferation.
The aim of this study was to examine the relationship between COX-2 or p53
expression and clinico-pathological characteristics including tumor cell
proliferation in gastric cancer. COX-2 and p53 expressions were investigated with
immunostaining, in tissue specimens obtained from 119 patients who underwent
surgery for gastric cancer. The Ki-67 labeling index (LI) was counted by Ki-67
immunostaining. COX-2 and p53 expressions correlated significantly with depth of
tumor invasion. However, there was no association between COX-2 or p53 expression
and survival. p53 expression did not correlate with COX-2 expression. There was
no significant difference in various clinicopathological variables between Ki-67
LI subgroups. The mean Ki-67 LI value of COX-2 positive tumors was significantly
higher than that of negative tumors. The mean Ki-67 LI value of p53 positive
tumors was not significantly higher than that of negative tumors. The mean Ki-67
LI value of both COX-2 and p53 positive tumors was significantly higher than that
of both negative tumors. These results imply that COX-2 expression is associated
with tumor cell proliferation of gastric cancer.
PMID- 17043423
TI - Overexpression of CIITA in T cells aggravates Th2-mediated colitis in mice.
AB - The MHC class II transactivator (CIITA) is the master transcriptional regulator
of genes involved in MHC class II restricted antigen presentation. Previously we
suggested another role of CIITA in Th1/Th2 balance by demonstrating that forced
expression of CIITA in murine T cells repressed Th1 immunity both in vitro and in
vivo. However, the results were contradictory to the report that CIITA functioned
to suppress the production of Th2 cytokine by CD4+ T cells in CIITA deficient
mice. In this study, we investigated the influence of constitutive expression of
CIITA in T cells on Th2 immune response in vivo using murine experimental colitis
model. In the dextran sodium sulfate-induced acute colitis, a disease involving
innate immunity, CIITA transgenic mice and wild type control mice showed similar
progression of the disease. However, the development of oxazolone-induced
colitis, a colitis mediated by predominantly Th2 immune response, was aggravated
in CIITA-transgenic mice. And, CD4+ T cells from the mesenteric lymph node of
CIITA-transgenic mice treated with oxazolone exhibited a high level of IL-4
secretion. Together, these data demonstrate that constitutive expression of CIITA
in T cells skews immune response to Th2, resulting in aggravation of Th2-mediated
colitis in vivo.
PMID- 17043424
TI - Antibiotic prophylaxis using third generation cephalosporins can reduce the risk
of early rebleeding in the first acute gastroesophageal variceal hemorrhage: a
prospective randomized study.
AB - Bacterial infection may be a critical trigger for variceal bleeding. Antibiotic
prophylaxis can prevent rebleeding in patients with acute gastroesophageal
variceal bleeding (GEVB). The aim of the study was to compare prophylactic third
generation cephalosporins with on-demand antibiotics for the prevention of
gastroesophageal variceal rebleeding. In a prospective trial, patients with the
first acute GEVB were randomly assigned to receive prophylactic antibiotics
(intravenous cefotaxime 2 g q 8 hr for 7 days, prophylactic antibiotics group) or
to receive the same antibiotics only when infection became evident (on-demand
group). Sixty-two patients in the prophylactic group and 58 patients in the on
demand group were included for analysis. Antibiotic prophylaxis decreased
infection (3.2% vs. 15.5%, p=0.026). The actuarial rebleeding rate in the
prophylactic group was significantly lower than that in the on-demand group
(33.9% vs. 62.1%, p=0.004). The difference of rebleeding rate was mostly due to
early rebleeding within 6 weeks (4.8% vs. 20.7%, p=0.012). On multivariate
analysis, antibiotic prophylaxis (relative hazard: 0.248, 95% confidence interval
(CI): 0.067-0.919, p=0.037) and bacterial infection (relative hazard: 3.901, 95%
CI: 1.053-14.448, p=0.042) were two independent determinants of early rebleeding.
In conclusion, antibiotic prophylaxis using third generation cephalosporins can
prevent bacterial infection and early rebleeding in patients with the first acute
GEVB.
PMID- 17043425
TI - Expression of the RERG gene is gender-dependent in hepatocellular carcinoma and
regulated by histone deacetyltransferases.
AB - Ras-related, estrogen-regulated, and growth-inhibitory gene (RERG) is a novel
gene that was first reported in breast cancer. However, the functions of RERG are
largely unknown in other tumor types. In this study, RERG expression was analyzed
in hepatocellular carcinomas of human patients using reverse transcriptase PCR
analysis. In addition, the possible regulation of RERG expression by histone
deacetyltransferases (HDACs) was studied in several cell lines. Interestingly,
the expression of RERG gene was increased in hepatocellular carcinoma (HCC) of
male patients (57.9%) but decreased in HCC of females (87.5%) comparison with
paired peri-tumoral tissues. Moreover, RERG gene expression was increased in
murine hepatoma Hepa1-6 cells, human breast tumor MDA-MB-231 cells, and mouse
normal fibroblast NIH3T3 cells after treated by HDAC inhibitor, trichostatin A.
Our results suggest that RERG may function in a gender-dependent manner in
hepatic tumorigenesis and that the expression of this gene may be regulated by an
HDAC-related signaling pathway.
PMID- 17043426
TI - Prophylactic low-dose heparin or prostaglandin E1 may prevent severe veno
occlusive disease of the liver after allogeneic hematopoietic stem cell
transplantation in Korean children.
AB - Studies investigating the effect of prophylactic drugs on hepatic veno-occlusive
disease (VOD) development are rare in children that have undergone allogeneic
hematopoietic stem cell transplantation (HSCT). This study examined risk factors
for VOD, the effect of prophylactic low-dose heparin or lipo-prostaglandin E1
(lipo-PGE1) and the survival rate at day +100 in children undergoing allogeneic
HSCT. Eighty five children underwent HSCT between June 1997 and September 2004.
Patients were diagnosed and classified as having mild, moderate or severe VOD
according to Seattle clinical criteria. Among 85 patients, 25 (29%) developed
VOD. VOD occurred more frequently in patients receiving busulfan-based
conditioning (24/65, 37%) than in those receiving TBI-based (1/10, 10%) or other
(0/10, 0%) regimens (p<0.05). The incidence of VOD was lower in patients with non
malignant disease compared to those with malignant disease (p<0.05). Survival at
day +100 for non-VOD patients was better than that for VOD patients (92% vs. 76%,
p<0.05). No patients receiving prophylactic heparin or lipo-PGE1 were found to
develop severe VOD, whereas 5 of 35 patients not receiving such prophylaxis
developed severe VOD. Given severe VOD is associated with a high mortality rate,
this study indicates that prophylactic heparin or lipo-PGE1 may decrease
mortality in children undergoing HSCT.
PMID- 17043427
TI - Increased expression of heat shock protein 72 protects renal proximal tubular
cells from gentamicin-induced injury.
AB - The nephrotoxicity of gentamicin (GM) has been widely recognized. Heat shock
protein 72 (HSP72) has been reported to be a cytoprotectant. However, its
cytoprotective effect against GM induced kidney injury has not yet been studied.
In this study, we investigated the cytoprotective effect of HSP72 on GM-induced
nephrotoxicity in vitro. Human Kidney tubular cell line, HK-2 cells were divided
into four groups: control group, GM group (cells incubated with GM only), heat
shock (HS) group (cells incubated at 43 degrees C for 30 min), and GM plus HS
group, respectively. Lactate dehydrogenase (LDH) release increased time
dependently from 24 hr to 96 hr compared to the data of cells treated with GM
only. Results of NAG activities, superoxide dismutase (SOD) activities and
malondialdehyde (MDA) content were similar to that of the LDH release. The amount
of HSP72 positive cells increased significantly at 72 hr after cells were treated
with GM only. Both HSP72 protein and gene expression increased significantly at
72 hr when cells were treated with GM. On the other hand, HS induced HSP72
expression markedly. Pretreatment of HS inhibited HK-2 cells from GM-induced
injury. It could reduce LDH release and NAG activity. HS also increased SOD
activity, and decreased MDA content when cells were damaged by GM. These findings
suggested that HS may protect kidney cells from GM-induced injury. Pre-induction
of HSP72 may provide therapeutic strategies for nephrotoxicity induced by GM.
PMID- 17043428
TI - Diagnostic relevance of pressure-controlled discography.
AB - Discogenic pain is a leading cause of chronic low back pain. The authors
investigated the efficacy of pressure-controlled discography to determine its
role in clinical decision-making for the management of patients with discogenic
pain. Pressure-controlled discography was performed in 21 patients (51 discs)
with pain-provocation, followed by post-discography computerized tomography
scans. Pain response was classified as positive response and negative response,
and measured with visual analog scale scores. Discographic findings were graded
by the modified Dallas discogram scale. Elastance, pain provocation on
intradiscal pressure, pressure and volume of initial pain response, and pain
response intensity were statistically analyzed. Elastance showed significant
differences between Grade 0 and Grade 4 and 5. Decreased elastance with positive
pain response group was a good indicator to imply that disc degeneration
presumably is a pain generator. Results of pain response were well correlated
with intradiscal pressure but not with the amount of injected volume. Among 31
discs of Grade 4 and 5, 74% showed negative pain response and 26% showed positive
response. It was concluded that pressure-controlled discography was useful to
diagnose discogenic pain and excellent guide in decision-making for spinal
operations.
PMID- 17043429
TI - The changes of skin temperature on hands and feet during and after T3
sympathicotomy for palmar hyperhidrosis.
AB - Unilateral thoracic sympathectomy in patients with palmar hyperhidrosis causes a
skin temperature drop in the contralateral hand. A cross-inhibitory effect by the
post-ganglionic neurons innervating hands is postulated as a mechanism of
contralateral vasoconstriction. The purpose of our study was to evaluate whether
this cross-inhibitory effect also occurs in the feet. Twenty patients scheduled
for thoracoscopic sympathicotomy due to palmar hyperhidosis were studied. Right
T3 sympathicotomy was performed first, followed by left T3 sympathicotomy. The
thenar skin temperatures of both hands and feet were continuously monitored using
a thermometer and recorded before induction of anesthesia, during the operation,
4 hr after and 1 week later. Following right T3 sympathicotomy, the skin
temperature of the ipsilateral hand gradually increased, however the skin
temperature of the contralateral hand gradually decreased. Immediately after
bilateral sympathicotomy, the skin temperature differences between hands and feet
increased, but these differences decreased 1 week later. Our results show that
cross-inhibitory control may exist in feet as well as in the contralateral hand.
Thus, the release of cross-inhibitory control following T3 sympathicotomy results
in vasoconstriction and decrease of skin temperature on the contralateral hand
and feet. One week later, however, the temperature balance on hands and feet
recovers.
PMID- 17043430
TI - Endothelial nitric oxide gene T-786C polymorphism and subarachnoid hemorrhage in
Korean population.
AB - We aimed to elucidate whether the eNOS T-786C mutant allele is implicated in
subarachnoid hemorrhage (SAH) susceptibility or vasospasm after SAH, and whether
the mutant allele is differentially expressed in those with small and large
ruptured aneurysms in Korean population. 136 consecutive patients diagnosed with
aneurismal SAH and 113 controls were recruited. Polymerase chain reaction and
direct sequencing of both strands were performed to determine genotypes with
respect to the eNOS T-786C mutation. No significant difference was found between
cases and controls with respect to the distributions of the two eNOS T-786C
single nucleotide polymorphism (SNP) genotypes. No significant differences in the
distributions of the eNOS T-786C SNP genotypes were found with regard to the
sizes of ruptured aneurysms or the occurrence of vasospasm after SAH. Multiple
logistic regression analysis after controlling for age and sex showed the eNOS T
786C SNP T/C geno-type was independently associated with an unfavorable outcome
(GOS grade 3-5) of SAH (Exp (beta)=4.27, 95% CI 1.131-16.108, p=0.032). In
conclusion, the eNOS T-786C mutation was not found to be associated with either a
susceptibility to SAH or vasospasm after SAH, or with aneurysm size in Korean
population. The eNOS T-786C SNP T/C genotype could be used as a prognostic marker
in individuals with SAH.
PMID- 17043431
TI - Abdominal ultrasonography findings in patients with spinal cord injury in Korea.
AB - This is a retrospective study of 500 patients with spinal cord injury who
underwent abdominal ultrasonography as a routine screening test from 2000 to
2003. We analyzed the results according to the different abdominal organ systems.
Among the 500 cases, 226 (45.2%) showed abnormal findings. 98 cases of abnormal
findings in the liver included 75 of fatty liver and 13 of mass. The 88 cases of
abnormal findings in the bladder included 56 of bladder wall thickening, 14 of
cystitis and 10 of urinary stone. The 35 cases of abnormal findings in the kidney
included 19 of renal cyst and 6 of pelvic dilatation. The 35 cases with
gallbladder abnormalities included 19 with gallstones and 11 with biliary sludge.
Excluding the cases with bladder wall thickening, there were still 170 cases with
abnormal ultrasonographic findings. Abdominal sonography seems to be a useful
tool in detecting hidden intraabdominal pathologies in patients with spinal cord
injury.
PMID- 17043432
TI - A case of imported Plasmodium ovale malaria.
AB - There have been reports in Korea of imported malaria cases of four Plasmodium
species, but there has been no report of imported Plasmodium ovale malaria
confirmed by molecular biological methods. We report an imported case of that was
confirmed by Wright-Giemsa-stained peripheral blood smear and nested polymerase
chain reaction targeting the small subunit ribosomal RNA gene. The amplified DNA
was sequenced and compared with other registered P. ovale isolates. The isolate
in this study was a member of the classic type group. The patient was a 44-yr-old
male who had worked as a woodcutter in Cote d'Ivoire in tropical West Africa. He
was treated with hydroxychloroquine and primaquine and discharged following
improvement. In conclusion, P. ovale should be considered as an etiology in the
imported malaria in Korea, because the number of travelers to P. ovale endemic
regions has recently increased.
PMID- 17043433
TI - A case of leukemic pleural infiltration in atypical chronic myeloid leukemia.
AB - Pleural effusion in chronic myeloid leukemia (CML) is poorly understood and
rarely reported in the literature. When the pleural effusion is caused by
leukemic pleural infiltration, the differential white blood cell count of the
effusion is identical to that of the peripheral blood, and the fluid cytology
reveals leukemic blasts. We report here a case of bilateral pleural involvement
of atypical CML in an 83-yr old male diagnosed with pancreatic cancer with
abdominal wall metastasis and incidental peripheral leukocytosis. Based on bone
marrow examination, chromosome analysis and polymerase chain reaction he was
diagnosed with Philadelphia chromosome negative, BCR/ABL gene rearrangement
negative CML. Following 3 months of treatment with gemcitabine for pancreatic
cancer, he developed bilateral pleural effusions. All stages of granulocytes and
a few blasts were present in both the pleural fluid and a peripheral blood smear.
After treatment with hydroxyurea and pleurodesis, the pleural effusion resolved.
PMID- 17043434
TI - Primary cardiac sarcoma in pregnancy: a case report.
AB - Primary cardiac sarcoma is a rare disease in adults. It is also associated with
poor prognoses, due to diagnostic delay, therapeutic difficulty, and high
metastatic potential. The coincidence of pregnancy and a primary cardiac intimal
sarcoma is extremely rare. We report a pregnant woman at 27(+5) weeks gestation
who was admitted to the hospital with acute-onset dyspnea. A mass was found on
the left atrium by transthoracic echocardiography. Subsequently, the intracardiac
mass was removed, and mitral valve replacement and modified DeVega tricuspid
annuloplasty were performed. The patient was diagnosed with a undifferentiated
sarcoma, and gave birth to a 1,230 g living baby boy by Caesarean section from
preterm contraction at 29(+5) weeks gestation. The patient then received systemic
chemotherapy. However, 10 months after the initial clinical onset, the patient
suddenly died. Surgery is the standard treatment for cardiac tumors, and their
removal should always be attempted, even in pregnant women. Although the overall
survival rates of the patients are rather poor, palliative cardiac surgery allows
the prolonging of pregnancy, until an acceptable fetal viability level is
reached.
PMID- 17043435
TI - Vibrio cholerae non-O1,non-O139 isolated from pleural effusion following total
gastrectomy.
AB - We isolated non-O1, non-O139 Vibrio cholerae from pleural effusion in a patient
with recurred advanced gastric cancer after total gastrectomy. We also recovered
the organism from the patient's stool culture. The patient did not experience
gastrointestinal symptoms such as diarrhea except heartburn and epigastric
discomfort from stomach cancer before admission. The suspected route of infection
is directly from the gastrointestinal tract through the previous surgical wounds.
After antibiotic treatment, no more V. cholerae was isolated and the patient was
well discharged from the hospital. This is the first report of V. cholerae
infection associated with pleural effusion in a long-term latent carrier of the
organism.
PMID- 17043436
TI - Etanercept-induced systemic lupus erythematosus in a patient with rheumatoid
arthritis.
AB - Tumor necrosis factor (TNF) is known to play a critical role in the pathogenesis
of rheumatoid arthritis (RA). Etanercept is a recombinant soluble fusion protein
of TNF alpha type II receptor and IgG, which acts as a specific TNF-alpha
antagonist. Anti-TNF-alpha therapy has been an important advance in the treatment
of RA. However, induction of autoantibodies in some proportion of patients
treated with TNF alpha inhibitors raised concerns for development of systemic
autoimmune diseases such as systemic lupus erythematosus (SLE). Although new
autoantibody formation is common with anti-TNF alpha therapy, there are only rare
reports of overt SLE, most of which manifested without major organ involvement
and resolved shortly after discontinuation of the therapy. We describe a 55-yr
old Korean woman who developed overt life threatening SLE complicated by
pneumonia and tuberculosis following etanercept treatment for RA. This case is to
our knowledge, the first report of etanercept-induced SLE in Korea.
PMID- 17043437
TI - Cavernous angioma in the falx cerebri: a case report.
AB - Intracranial cavernous angiomas are benign vascular malformations and can be
divided into intra-axial and extra-axial lesions. Extra-axial cavernous angiomas
are relatively rare and usually arise in relation to the dura mater and mimick
meningiomas. We report a case of cavernous angioma that occurred in the falx
cerebri of a 22-yr-old female patient with the special focus on neuroradiologic
findings. This is the fourth case of cavernous angioma in the falx cerebri
reported in the literature to our knowledge.
PMID- 17043438
TI - A case of infantile Alexander disease accompanied by infantile spasms diagnosed
by DNA analysis.
AB - Alexander disease (AD) is a rare leukodystrophy of the central nervous system of
unknown etiology. AD is characterized by progressive failure of central
myelination and the accumulation of Rosenthal fibers in astrocytes, and is
inevitably lethal in nature. Symptomatically, AD is associated with
leukoencephalopathy with macrocephaly, seizures, and psychomotor retardation in
infants, and usually leads to death within the first decade. Its characteristic
magnetic resonance imaging (MRI) findings have been described as demyelination
predominantly in the frontal lobe. Moreover, dominant mutations in the GFAP gene,
coding for glial fibrillary acidic protein (GFAP), a principal astrocytic
intermediate filament protein, have been shown to lead to AD. The disease can now
be detected by genetic diagnosis. We report the Korean case of an 8-month-old
male patient with AD. He was clinically characterized due to the presence of
psychomotor retardation, megalencephaly, spasticity, and recurrent seizures
including infantile spasms which is a remarkable presentation. Demyelination in
the frontal lobe and in a portion of the temporal lobe was demonstrated by brain
MRI. Moreover, DNA analysis of peripheral blood showed the presence of a R239L
mutation in the GFAP gene, involving the replacement of guanine with thymine.
PMID- 17043439
TI - Intracranial dural arteriovenous fistula draining into spinal perimedullary
veins: a rare cause of myelopathy.
AB - We report a rare case of progressive myelopathy caused by intracranial dural
arteriovenous fistula with venous drainage into the spinal perimedullary veins. A
45-yr-old man developed urinary and fecal incontinence and muscle weakness in the
lower limbs. Magnetic resonance imaging revealed brainstem edema and dilated
veins of the brainstem and spinal cord. Cerebral angiography showed a dural
arteriovenous fistula fed by the neuromeningeal branch of the left ascending
pharyngeal artery. Occlusion of the fistula could be achieved by embolization
after a diagnostic and subsequent therapeutic delay. There was no improvement in
clinical condition. For the neurologic outcome of these patients it is important
that fistula must be treated before ischemic and gliotic changes become
irreversible.
PMID- 17043440
TI - COXIBs: interpreting the swell of phase IV data.
PMID- 17043441
TI - Association of primary biliary cirrhosis and rheumatoid arthritis.
AB - Primary biliary cirrhosis (PBC) and rheumatoid arthritis (RA) are chronic medical
conditions in which, although the etiology is uncertain, autoimmune features
predominate. These two conditions are, in fact, multisystemic diseases, with a
multitude of manifestations that are not limited to their target end organ. It
has been well established that patients with PBC may have musculoskeletal
complaints and patients with RA may have evidence of hepatic dysfunction. Both of
these conditions are fairly rare, with RA being found in approximately 1% of the
population and PBC being found in approximately 20/100,000 women and 2/100,000
men.The likelihood of these uncommon conditions occurring in the same patient is
very rare and unusual. We have identified a unique group of 25 patients who have
met disease-defining criteria for both RA and PBC. Awareness of this combination
should prompt rheumatologists to assess for PBC with antimitochondrial antibody
testing in patients with abnormal liver tests and also to raise awareness that
abnormal liver tests in RA patients are not always due to drugs.
PMID- 17043442
TI - Patient perception of the burden of weight gain and blood pressure increase among
RA patients using celecoxib, rofecoxib, and non-specific NSAIDs.
AB - Nonsteroidal anti-inflammatory medications (NSAIDs) may be accompanied by
clinically important renal side effects. We compared the rate of reported side
effects from celecoxib, rofecoxib, and nonspecific (NS) NSAIDs and their burden
in RA patients. Patients on rofecoxib were more likely to report a problem with
weight gain (P < 0.05) and an increase in blood pressure (P < 0.001). In
addition, rofecoxib users were 28% more likely to be in a more severe category
for being bothered by unintentional weight gain (OR = 1.28, P < 0.05) and 53%
more likely to state that they were in a more severe category for blood pressure
increase (OR = 1.53, P < 0.000), compared with patients receiving celecoxib.
Weight gain and blood pressure were also increased by coexisting cardiovascular
disease. Clinicians should be aware that patient-reported weight gain and
increases in blood pressure can occur with all NSAIDs, and may be particularly
increased with rofecoxib. Existing cardiovascular disease is also an independent
predictor of weight gain and increased blood pressure.
PMID- 17043443
TI - A patient with wegener granulomatosis and intraventricular hemorrhage.
AB - We report a case of intraventricular hemorrhage (IVH) in a 27-year-old man with
Wegener granulomatosis (WG), successfully treated with corticosteroids and
cyclophosphamide. Neurologic manifestations occur in 22%-54% of patients with WG,
with cerebral vasculitis in less than 5%. Only 2 cases of IVH associated with WG
have been reported at autopsy. This is the first reported case of in situ IVH
associated with WG in a patient who survived. In patients with WG who present
with neurologic manifestations, cerebral vasculitis with secondary intracranial
hemorrhage should be considered, as these patients are often resistant to
immunosuppressive therapies and may present with normal angiograms.
PMID- 17043444
TI - Thiemann disease.
AB - Thiemann disease is a rare genetic disorder that is considered to be a form of
avascular necrosis of the proximal interphalangeal joints of the fingers and
toes. The clinical symptoms usually appear in adolescence or puberty and may be
confused with juvenile rheumatoid arthritis. The characteristic symmetrical,
firm, relatively painless deformity and x-ray findings of the epiphysical
irregularities should suggest the diagnosis. As rheumatologists become more
familiar with the disease, it may be more frequently and promptly diagnosed.
PMID- 17043445
TI - Cellulitis and septic arthritis caused by Campylobacter fetus and Campylobacter
jejuni: report of 2 cases and review of the literature.
AB - Bacteremia caused by gram-negative bacteria occasionally causes soft tissue
infections, including cellulitis and septic arthritis. We describe 1 patient each
with Campylobacter fetus cellulitis and septic arthritis and review the world
literature with regard to C. fetus and C. jejuni infections at these sites.
Altogether, 14 patients with cellulitis (12 due to C. fetus and 2 due to C.
jejuni) and 20 patients with septic arthritis (15 due to C. fetus and 4 caused by
C. jejuni) have been described. Most infections, particularly those causing
cellulitis, are found in elderly men with underlying systemic disease. Most
patients are febrile but less than half manifest a leukocytosis. There were only
3 deaths in this series of 33 patients. The newer macrolides, including
azithromycin and clarithromycin, are considered the drugs of choice, particularly
with C. jejuni, while soft tissue infections caused by C. fetus respond nicely to
many beta-lactams, particularly to cephalosporins and carbapenems, as well as to
macrolides and quinolones.
PMID- 17043446
TI - Soft tissue metastases presenting as greater trochanteric pain syndrome.
AB - Greater trochanteric pain syndrome includes a complex differential diagnosis. We
report the case of a 71-year-old woman who consulted us because of pain in the
lateral aspect of the hip. A diagnosis of greater trochanter bursitis was
suggested, and she was treated with local injections of a mixture of
corticosteroids plus anesthetic, but the condition did not improve. A pelvic MRI
showed a high intensity signal in the gluteus medius and minimus and a subsequent
biopsy revealed a metastasis of an adenocarcinoma of unknown origin. Although
pain on the lateral aspect of the hip is often attributed to trochanteric
bursitis, other diagnoses, including this rare finding of malignant disease,
should be considered in the differential diagnosis of the greater trochanteric
pain syndrome.
PMID- 17043447
TI - Oncogenic hypophosphatemic osteomalacia associated with a nasal
hemangiopericytoma.
AB - We report a patient with a nasal hemangiopericytoma associated with an oncogenic
hypophosphatemic osteomalacia (OHO). This syndrome results from tumor products
that decrease renal tubular phosphate resorption, leading to the osteomalacia.
This patient presented with classic bone manifestations of osteomalacia and a
nasal tumor. Laboratory studies performed before the first resection of the tumor
included normal serum calcium, hypophosphatemia due to decreased tubular
reabsorption of phosphate, and an undetectable serum 1,25 dihydroxy vitamin D
level. Serum parathormone level was normal. Anterior iliac crest bone biopsy
showed characteristic signs of osteomalacia that included increased osteoid and
delayed mineralization. A partial resection of the nasal tumor was performed.
After the first surgery the patient showed detectable serum level of 1,25
dihydroxy vitamin D, and transient normalization of the tubular reabsorption of
phosphate. The patient was also treated with phosphate supplements and vitamin D
with transient control of her clinical manifestations and improvement of the
radiographic signs of osteomalacia. Three months after surgery, the serum level
of 1,25 dihydroxy vitamin D level again became undetectable. After selective
embolization of the tumor, followed by an apparent complete tumor resection and
postoperative radiation therapy, her hypophosphatemia and decreased phosphate
tubular reabsorption persisted. Therefore, biochemical changes associated with
hemangiopericytoma induced OHO may persist even after apparent total tumor
resection. Clinicians should be aware of the oncogenic basis for some
osteomalacia, as seen in this patient.
PMID- 17043448
TI - Tophaceous gout in a patient with thalassemia.
AB - We report a 46-year-old Greek female with thalassemia intermedia, who presented
to our hospital with end stage renal disease of unknown etiology and tophaceous
gout. In addition, skeletal manifestations characteristic of thalassemia were
noted with massive extramedullary hematopoiesis presenting as posterior
mediastinal masses. We report the first case in English literature of crystal
proven gout in thalassemia intermedia and provide a review of the literature that
indicates the relative rarity of gout in this clinical setting, despite evidence
of urate overproduction in one report. The long survival and renal insufficiency
may have contributed to our patients' tophaceous gout.
PMID- 17043449
TI - Anticipating rather than confirming drug toxicity through selective laboratory
testing.
PMID- 17043450
TI - Epidemiology of Wegener granulomatosis since the introduction of ANCA testing in
Olmsted County, MN, 1990-1999.
PMID- 17043451
TI - Color Doppler ultrasound of the hand: observations on clinical utility in
rheumatoid arthritis.
AB - The use of ultrasound with color Doppler in the evaluation of rheumatoid
arthritis was followed in 25 patients with joint complaints. Small joint
ultrasound of the metacarpophalangeal joints (MCPs) as well as the wrists was
performed with supplementation by color Doppler. In addition, 6 patients were
followed for at least 3 months after start of treatment of rheumatoid arthritis
using the same technique. In patients with what appeared to be definite
rheumatoid arthritis, ultrasound supported this diagnosis as evidenced by the
finding of cortical defects, extensor tendon sheath thickening, and synovial
proliferation. Increased activity by color Doppler ultrasonography was the most
common finding. Significant decrease in color Doppler activity was noted in the 6
patients who were followed up after 3 months of therapy with disease-modifying
agents. Therefore, the use of ultrasound with color Doppler could aid in the
diagnosis and follow up of patients with rheumatoid arthritis.
PMID- 17043452
TI - Health-related quality of life and support group attendance for patients with
systemic lupus erythematosus.
AB - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with
variable symptoms. Severity of disease has been associated with mental and
physical health-related quality of life (HRQoL). The potential effects of support
groups have not been examined. We examined the possible improvement in mental and
physical HRQoL of women with SLE who attended support groups. Thirty-four women
who attended support groups and 71 comparison women with SLE were recruited. Self
administered surveys included the Medical Outcomes Study Short-Form 36 (SF-36)
and a 3-level rating of disease activity.Mean SF-36 Mental Health Summary Scale
scores (MCS) were significantly lower for women attending groups (31.5) compared
with nonattending SLE women (39.8). MCS scores were lower for blacks compared
with whites (33.7 vs. 39.2, P <0.05). Women with high and moderate disease
activity had lower MCS scores compared with those with low activity (28.6 or 35.6
vs. 42.7, P <0.05). In linear regression, 27% of the variation in MCS was
explained by support group attendance, disease activity, race, and age.Overall,
women with SLE reported lower MCS and physical health summary scales (PCS) scores
than published population values, indicating markedly reduced quality of life.
Any potential positive effects of support groups will need to be tested in a
prospective random design to assess improvements in HRQoL.
PMID- 17043453
TI - How to keep a wet preparation of synovial fluid.
AB - Identification of crystals in the synovial fluid (SF) is mandatory for the
diagnosis of a microcrystal deposition arthropathy. In some cases, this analysis
can be troublesome, especially in medical centers where a qualified practitioner
is not continually present. Therefore, we investigated a method for preservation
of a wet preparation of SF for 24 hours at room temperature. The procedure
consisted in storing the preparation in a closed Petri plate whose bottom was
covered by a cellulose compress moistened with saline (0.9% sodium chloride)
separated from the slide by 2 wooden or glass sticks. The joint aspirates of 20
consecutive patients with various microcrystal arthropathies were read
immediately after aspiration and reviewed after 24 hours on the slides stored
according to the previously mentioned procedure. For 11 of the 20 cases, a second
SF preparation was stored in normal conditions. The amounts of crystals were
estimated semiquantitatively.Preparations stored in the Petri plates were clearly
readable after 24 hours and crystals still identifiable on each slide. The
amounts of crystals were still the same. After 24 hours, the preparations stored
in normal conditions were dry, the shapes of the crystals were blurred, their
amount was reduced, and birefringent artifacts were seen. In conclusion, when the
amounts of SF are small and a skilled technician or a rheumatologist is not
immediately available for reading the preparation, storing the wet preparation of
SF in a moistened Petri plate can prove useful.
PMID- 17043454
TI - Sarah's Knee: A Famous Actress With Chronic, Inflammatory Monoarthritis.
AB - Sarah Bernhardt had a recurrent and later persistent inflammatory arthritis of
her right knee for more than 25 years. She probably had pulmonary tuberculosis,
starting a dozen years before the arthritis, and her chronic synovitis may have
been tuberculous. Several months in a cast led to deterioration and later
amputation of the leg, an outcome that might have been prevented by surgical
arthrodesis. Despite the loss of her limb and progressive renal failure, she
continued an active theatrical career until her death at age 78.
PMID- 17043455
TI - Takayasu arteritis presenting with Fever of unknown origin: two case reports.
AB - Two patients with Takayasu arteritis are reported who presented with fever of
unknown origin. Takayasu arteritis was diagnosed at the prepulseless period after
stenotic lesions of the aorta, and its branches were seen with imaging methods.
In the first month of steroid treatment, hypertension developed in both patients
that was related to fibrosis in stenotic lesions in renal arteries. Both patients
were treated with percutaneous transfemoral renal angioplasty. Takayasu arteritis
should be considered in the differential diagnosis of fever of unknown origin,
especially in young women. Absence of the physical findings related to vasculitic
lesions will not rule out the disease, which can be seen in the prepulseless
period.
PMID- 17043456
TI - Elastofibroma dorsi: an unusual case of a subscapular nodular mass.
AB - Elastofibroma dorsi is a benign, slow-growing soft tissue tumor. Poorly
symptomatic, it raises an important differential diagnosis with benign and
malignant tumors of the subscapular region, and with a differential diagnosis
with shoulder pain and snapping scapula. It is seen in elderly women and occurs
more frequently in the subscapular region, although it has been reported in
several locations. We report the case of a 58-year-old woman who presented with
upper gastrointestinal bleeding. During the physical examination, a mass was
found in the right subscapular region. Months later, the patient presented with
pain on right arm motion and an increase in the size of the mass. Complete
surgical excision was performed. The patient is free of symptoms with no
recurrences of the tumor so far. Consider this benign tumor if a lipoma-like
nodule or mass becomes symptomatic.
PMID- 17043457
TI - Tubulointerstitial Nephritis With Uveitis (TINU): A Syndrome Rheumatologists
Should Recognize: A Case Report and Review of the Literature.
AB - Patients with uveitis such as the patient whose case is reported here are often
referred to rheumatologists for investigation of possible underlying systemic
diseases. This patient presented with decreased vision, photophobia, weight loss,
and fevers and was found to have uveitis, elevated creatinine, and interstitial
nephritis. This raised consideration of a variety of systemic diseases before she
was determined to have the tubulointerstitial nephritis with uveitis (TINU)
syndrome. The TINU syndrome, although known to some ophthalmologists and
nephrologists, is still rather obscure. Uncommon but not rare with 133 cases in
the literature, TINU syndrome should be one more diagnosis to be considered in
patients with uveitis. The median age of onset is 15, but it ranges from 9 to 74.
There is a 3:1 female preponderance. Response to corticosteroids, which are used
in 80% of reported cases, is rapid. The prognosis for the renal disorder is
excellent, although the uveitis often recurs or remains chronic.
PMID- 17043458
TI - Successful therapy of rheumatoid arthritis with rituximab: renewed interest in
the role of B cells in the pathogenesis of rheumatoid arthritis.
AB - Rheumatoid arthritis (RA) is often considered a T cell-mediated disease, yet
recent studies describe benefit with rituximab, a monoclonal antibody directed
against the B cell antigen CD20. We report our experience using rituximab for 5
patients with severe, disease-modifying antirheumatic drug (DMARD)-refractory RA.
Five patients with seropositive, erosive RA received rituximab as 4 weekly doses
of 375 mg/m. Four subjects experienced remission lasting 5 to 12 months after
noting lack of efficacy with antitumor necrosis factor (TNF) therapy. All
patients have relapsed, with signs and symptoms of RA returning a mean of 8
months after therapy. Rituximab appears to be a safe and potentially helpful
treatment of refractory RA and, until U.S. Food and Drug Administration approval,
could be considered for compassionate use in people who have failed multiple
DMARDs. Individuals who do not respond to anti-TNF therapy could experience
arthritis that is perpetuated by B cell more than T cell function; these patients
could be most likely to respond to rituximab. Further studies are needed to
clarify the optimal dose and frequency of rituximab therapy, and its role in
combination therapy for individuals with RA.
PMID- 17043459
TI - Evidence-based soft tissue rheumatology: epicondylitis and hand stenosing
tendinopathy.
AB - Lateral and medial epicondylitis represent overuse tendinopathies of wrist
extensor and wrist flexor muscles, respectively. In lateral epicondylitis, a
short-term therapeutic efficacy of glucocorticoid injection and limited evidence
on the efficacy of acupuncture has been shown. De Quervain tendinopathy is caused
by tendinous impingement by a thickened retinaculum. There is limited evidence on
the efficacy of glucocorticoid injection in this condition.Trigger finger usually
results from tendon entrapment beneath a thickened A1 flexor pulley. An
association with hand tool use and diabetes has been shown in this condition, and
there is evidence on the therapeutic efficacy of glucocorticoid injection. No
other therapeutic modality has shown efficacy or has been assessed in a placebo
controlled clinical trial in these conditions.It can be concluded that
epicondylitis and stenosing tendinopathy are readily diagnosed, and most patients
recover with current therapies. However, still unsolved issues preclude a purely
evidence-based approach to these entities.
PMID- 17043460
TI - Computed tomography does not support sacroiliitis as a feature of behcet disease:
a metaanalytic review.
PMID- 17043461
TI - Osteonecrosis of the femoral head resulting from excessive corticosteroid nasal
spray use.
PMID- 17043462
TI - The coincidence of ankylosing spondylitis and gouty arthritis.
PMID- 17043463
TI - Successful use of etanercept in a patient with pyoderma gangrenosum complicating
rheumatoid arthritis.
PMID- 17043464
TI - The prevalence and clinical impact of reported cognitive difficulties (fibrofog)
in patients with rheumatic disease with and without fibromyalgia.
AB - Cognitive dysfunction in patients with rheumatic disease encompasses a range of
impairment. Their prevalence, co-occurrence, and impact on symptom severity were
assessed in 57 patients with fibromyalgia (FMS) and 57 patients with rheumatic
disease without FMS. Information pertaining to memory decline, mental confusion,
and speech difficulty was extracted from questions embedded in a health
questionnaire and a blind retrospective chart review. Pain, morning stiffness,
fatigue, and sleep difficulty were established on a 0- to 100-mm visual analog
scale. Variables of mental confusion, fatigue, tension, depression, anger, and
vigor were assessed using the Profile of Mood States.Compared with the non-FMS
sample, patients with FMS complained more often of memory decline (70.2-24.6%),
mental confusion (56.1-12.3%), and speech difficulty (40.4-3.5%). Memory decline
and mental confusion were coupled more often in patients with FMS (50.9-8.8%).
Patients with FMS with this combination of cognitive problems reported more pain
(76.0-45.4%), stiffness (79.7-43.7%), fatigue (79.6-52.6%), and disturbed sleep
(59.2-36.6%) compared with patients with FMS with memory problems alone. Patients
with rheumatic disease substantially differ in cognitive vulnerability, with
patients with FMS at considerably higher risk for cognitive difficulty. More
importantly, the prevalence of a combined disturbance in memory and mental
clarity is high and closely associated with the perception of increased illness
severity and diminished mental health in FMS. That this linkage has the
possibility of having a great deal to do with an important clinical variant of
FMS underscores the need for greater clinical recognition of this underrecognized
pattern and for further research.Patients with fibromyalgia frequently report
memory and concentration problems, especially if asked about them. Clinicians
could judge these complaints as similar to adult attention deficit syndrome and
reassure the patient. Trying medication to improve attention and concentration is
sensible but untested in fibromyalgia.
PMID- 17043465
TI - Pilot investigation of hyaluronate injections for first metacarpal-carpal (MC-C)
osteoarthritis.
AB - Hyaluronate intraarticular injections are widely used for treatment of pain
associated with osteoarthritis of the knee, but there is no published literature
on its use in osteoarthritis of the hand. We describe an open-label, baseline
controlled pilot study in which 5 weekly injections of 10 mg sodium hyaluronate
(molecular weight 500-730 kDa) in 1 mL was used to treat 16 patients with
osteoarthritic first metacarpal-carpal (MC-C) joints. The injections were
performed easily and were well tolerated. Mean pain score at 5 months after the
last injection, on a 10-point visual analog scale, decreased from 4.74 to 2.56 at
rest. Pain on use decreased from 5.91 to 4.33. Pinch strength and a short
questionnaire on hand function did not significantly change. The results of this
small pilot study suggest that intraarticular injections into the first MC-C
joint are easily administered, well tolerated, and could be an effective
treatment option for patients with osteoarthritis of this joint. Further
investigation using larger, blind controlled clinical studies are warranted.
PMID- 17043467
TI - Inflammatory arthritis of the hands as expressed by the impressionists in the
Orsay Museum.
AB - An extensive study looking for signs of inflammatory arthritis in the paintings
of the impressionists was performed at the Orsay Museum in Paris, France. Of the
435 paintings reviewed, 3 works by different painters were found to show signs of
inflammatory arthritis of the hands. We suspect that the importance of the
arthritis in the models' lives led the painters to emphasize this condition in
their paintings.
PMID- 17043468
TI - Coronary vasculitis with acute myocardial infarction in a young woman with
systemic lupus erythematosus.
AB - Myocardial infarction in patients with systemic lupus erythematosus (SLE) is most
commonly a consequence of atherosclerosis. Coronary vasculitis with aneurysms is
a rare cause of myocardial ischemia in SLE. We present a case of a 22-year-old
woman with a 4-year history of SLE who was admitted with acute onset of chest
pain. Although initially treated for lupus pericarditis, she was subsequently
found to have an acute myocardial infarction. Cardiac catheterization revealed
multiple areas of aneurysmal coronary dilatation and only moderate stenoses of
the secondary branches.In view of the angiographic findings, coronary
revascularization was not indicated. Anticoagulant therapy was initiated as a
result of the presence of large aneurysmal coronary dilatations, which are
predisposed to in situ thrombosis and distal embolization. The coronary
vasculitis was treated with immunosuppressive therapy. Measures aimed at
secondary prevention of coronary artery disease, including optimization of lipid
profile, blood pressure control, and prevention of left ventricular postinfarct
remodeling, were initiated and continued indefinitely.
PMID- 17043469
TI - Whipple disease revisited: radiographic features of a patient with 35 years of
undiagnosed arthritis.
AB - Whipple disease is a relatively rare systemic disorder with protean
manifestations among which arthropathic involvement is a frequently attendant and
early manifestation. We report the second of 2 consecutively diagnosed Whipple
patients seen in an outpatient rheumatology practice who exhibited the triad of
the singularly seldom reported radiographic findings of sacroiliitis, cervical
apophyseal fusion, and pancarpal narrowing is reported. Both unexplained
recurrent arthritis and these radiographic features should lead one to consider
this treatable disease.
PMID- 17043470
TI - Spinal gout: case report and review of the literature.
AB - Spinal involvement is considered to be a rare complication of gout. We report a
case of a 48-year-old woman with chronic tophaceous gout, recently desensitized
to allopurinol, who presented with an L4 radiculopathy. A magnetic resonance
image (MRI) of the lumbosacral spine revealed an extradural process at L4 level.
Three months before this episode, for unrelated reasons, the patient had an MRI
of her entire spine, which was normal. Laminectomy was performed revealing a
large gouty tophus. The fact that a large gouty tophus formed over this short a
period of time causing neurologic symptoms highlights the importance of
aggressive medical management of patients with longstanding tophaceous gout with
urate-lowering agents. Spinal extradural gout could lead to neurologic deficits
necessitating emergent surgery for decompression, exposing the patient to further
risk. Every effort should be made to lower the serum uric acid level by
maximizing the pharmacologic regimen and, if necessary, desensitizing the
patient, like in our case, if there is a history of allergy to allopurinol.
PMID- 17043471
TI - Benign angiopathy of the central nervous system.
AB - Apparent central nervous system vasculitis could have a benign course in a subset
of patients and is referred to as benign angiopathy of the central nervous system
(BACNS). This is mostly is seen in young women and presents with acute onset of
neurologic symptoms, usually in the form of severe headache and/or a focal
neurologic event. Cerebrospinal fluid analysis could be normal or nearly normal.
Brain angiogram typically shows segmental narrowing, ectasia, or beading in
multiple vascular territories on brain angiogram. Like in all cases of CNS
vasculitis, exclusion of other systemic diseases or its mimickers associated with
cerebral involvement is important.BACNS could respond favorably to treatment with
corticosteroids alone or in combination with a calcium channel blocker, thereby
avoiding unnecessary and prolonged treatment with other immunosuppressants like
cyclophosphamide with their side effects. Little is published in the literature
about BACNS, but is a rapidly emerging concept. It is thus important to
recognize. We report a patient with classic presentation of BACNS to highlight
the significance of distinguishing benign angiopathy from the more aggressive
form of CNS vasculitis, because the treatment and response varies in these 2
entities.
PMID- 17043472
TI - Relapsing polychondritis with encephalitis.
AB - Central nervous system manifestations are rare in patients with relapsing
polychondritis. We report a case of encephalitis associated with relapsing
polychondritis. The patient presented with bilateral auricular chondritis first
and then tracheal chondritis, and encephalitis developed. The symptoms and signs
of encephalitis were felt mostly likely to be the result of vasculitis and
improved dramatically after pulse corticosteroid therapy. We believe that early
recognition of central nervous system involvement in relapsing polychondritis is
extremely important. High-dose corticosteroids should be given to suspected cases
as early as possible.
PMID- 17043473
TI - Beaver fever arthritis.
AB - Giardia lamblia, a flagellated protozoan and common cause of gastroenteritis, is
a rare but previously reported cause of reactive arthritis (ReA). We report a
case of inflammatory oligoarthritis in a young woman after infection with
Giardia. Two weeks after being treated, she developed an inflammatory arthritis
of her left knee and right elbow that was refractory to nonsteroidal
antiinflammatory medication. Antinuclear antibody, rheumatoid factor, and HLA-B27
tests were negative. She had almost immediate relief with intraarticular
injection of corticosteroids. We review the previously reported cases of ReA
following giardiasis and discuss possible pathogenic mechanisms. Although ReA
most commonly occurs after chlamydial urethritis or gastroenteritis associated
with typical enteropathic bacteria, important historical clues could point to
less common pathogens such as Giardia. Physicians should be aware of these less
common causes of ReA, because this could have important diagnostic and
therapeutic implications.
PMID- 17043474
TI - Isolated vasculitis of the cervix presenting as vaginal discharge.
AB - A 44-year-old woman previously in excellent health presented with clear vaginal
discharge. Pelvic examination revealed a friable cervix that showed small-vessel
necrotizing vasculitis on cone biopsy. She had no clinical evidence of systemic
vasculitis or any connective tissue disease. Laboratory findings of inflammation
(raised erythrocyte sedimentation rate and thrombocytosis) returned to normal
after the cone biopsy. She has been symptom-free for over 2 years after the cone
biopsy and a subsequent hysterectomy that failed to reveal uterine vasculitis.
Localized vasculitis of the cervix can present as vaginal discharge or
menorrhagia without evidence of vasculitis elsewhere and does not require
systemic therapy.
PMID- 17043476
TI - Nocturnal neck pain relieved by aspirin.
PMID- 17043475
TI - The ACRONYM project.
PMID- 17043477
TI - The use of infliximab in a patient with steroid-dependent Churg-Strauss syndrome.
PMID- 17043478
TI - Women's Health Initiative perspective: what does it really mean to the
rheumatologist?
PMID- 17043479
TI - How many versions and translations of the HAQ and its variants are needed? It
doesn't matter-just use one.
PMID- 17043480
TI - Metabolic syndrome and ischemic heart disease in gout.
AB - BACKGROUND: For decades, gout has been associated with several metabolic
abnormalities and with ischemic heart disease (IHD). OBJECTIVE: Our aim was to
determine the prevalence of metabolic syndrome by Adult Treatment Panel III
criteria (ATP III) and ischemic heart disease (IHD) by electrocardiogram (EKG)
and/or single photon emission computed tomography (SPECT) in patients with gout.
METHODS: We included 64 consecutive outpatients with primary gout, but no history
of IHD, attending our clinic for the first time. Demographic and clinical data
were recorded and resting electrocardiogram, lipid profile, fasting insulin, and
SPECT with Tc sestamibi were performed. Metabolic syndrome was defined according
to ATP III criteria (> or =3 of the following data: 1) hyperglycemia (fasting
glucose > or =110 mg/dL) or previous diagnosis of diabetes mellitus, 2)
hypertension (> or =130/85 mm Hg) or previous diagnosis, 3) high-density
lipoprotein (HDL) <40 mg/dL (men) or <50 mg/dL (women), 4) triglycerides > or
=150 mg/dL, and 5) obesity. RESULTS: IHD was diagnosed in 10 patients (16%); 2
had EKG changes compatible with previous silent myocardial necrosis and the other
8 had abnormal SPECT. The prevalence of metabolic syndrome was 82%, all patients
had at least 1 metabolic abnormality, but all the patients with IHD had metabolic
syndrome (3 criteria according with ATP III). Patients with IHD differed from
those without IHD in the percentage of HDL levels <40 mg/dL (100% vs. 82%; P =
0.05) as well as glucose and insulin levels in the fasting state (129.3 +/- 6.1
mg/dL vs. 92.7 +/- 16.7 mg/dL; P = 0.000; and 21.1 +/- 6.0 vs. 17.5 +/- 8.6
UI/mL; P = 0.03) and low-density lipoproteins (143.9 +/- 21.3 mg/dL vs. 118.2 +/-
47.7 mg/dL; P = 0.014). In contrast, serum creatinine and urea (1.02 +/- 0.13
mg/dL vs. 1.5 +/- 1.5 mg/dL; P = 0.024; and 33.9 +/- 9.3 mg/dL vs. 48.7 +/- 46.1
mg/dL; P = 0.039) and creatinine clearance <50 mL/min (10% vs. 37%; P = 0.06)
were higher in patients without IHD. CONCLUSIONS: In this work, metabolic
syndrome was very common among patients with gout. Sixteen percent of the
patients, although previously asymptomatic, had IHD, they all had metabolic
syndrome. Gouty patients frequently first seek medical care from a
rheumatologist. The rheumatologist can have an important role in detecting
metabolic syndrome and risk factors for cardiovascular disease.
PMID- 17043481
TI - Validation and crosscultural adaptation of an argentine spanish version of the
health assessment questionnaire disability index.
AB - BACKGROUND: The Health Assessment Questionnaire (HAQ) is one of the most
frequently used instruments to assess functional capacity in activities of daily
living. OBJECTIVE: The objective of our study was to determine the
reproducibility and validity of an Argentinean version of the HAQ disability
index (HAQ-DI) in patients with rheumatoid arthritis (RA). METHODS: Consecutive
adult patients with RA from 3 different provinces in Argentina were included. The
original English version of the HAQ-DI was translated and adapted into Spanish by
3 rheumatologists and the final version back translated into English by a
bilingual person. The reproducibility of the questionnaire was assessed in 30
patients who came for a second visit 3 to 5 days later. The cross-sectional
construct validity was assessed by comparing the HAQ with classic parameters of
disease activity (number of swollen and tender joints, patient and physician
visual analog scale for pain and activity as well as functional class,
erythrocyte sedimentation rate, and C-reactive protein. RESULTS: Two hundred
patients with RA were included. The reproducibility was r = 0.97 (P = 1 x 10-5);
intraitem correlation analysis did not show any redundancy. Correlation between
HAQ-A and parameters of disease activity were all significant. A stepwise
multiple regression analysis showed that the main variables associated with HAQ-A
scores were visual analog scale for pain and duration of morning stiffness. A
weak although significant negative correlation was found between the HAQ-A and
economic level (r = -0.21, P = 0.03). The median time to complete the
questionnaire was 5 minutes and there were no problems with any questions.
CONCLUSION: This version of the HAQ-DI would allow for more availability so that
Spanish-speaking countries can select the version most suitable to their
sociocultural environment.
PMID- 17043482
TI - How valuable is screening for thyroid disease in patients with carpal tunnel
syndrome?
AB - BACKGROUND: It has been suggested that many patients with carpal tunnel syndrome
have associated thyroid or other metabolic diseases. METHODS: 206 patients with
clinical features suggestive of carpal tunnel syndrome (CTS), including those
with known underlying cause of CTS, were screened for thyroid dysfunction. Nerve
conduction studies were compatible with a diagnosis of CTS in 136 patients (CTS
group). RESULTS: We diagnosed only 2 new cases of hypothyroidism (1.5% of
patients in the CTS group) and none with hyperthyroidism. CONCLUSIONS: Thus
routine screening of patients with isolated CTS for thyroid function abnormality
does not appear to be worthwhile.
PMID- 17043483
TI - Sepsis as a possible adverse drug reaction in patients with rheumatoid arthritis
treated with TNFalpha antagonists.
AB - BACKGROUND: Clinical improvement during the treatment of rheumatoid arthritis
(RA) with the TNFalpha antagonists has been well documented. Our knowledge of
uncommon adverse drug reactions (ADRs) with these new drugs is more restricted.
Concerns have been raised that these types of drugs could cause an increased
frequency of infections, and already existing infections are named as
contraindications in the product labels. METHODS: In Sweden, it is compulsory for
healthcare professionals with permission to prescribe drugs to report suspected
ADRs to the regulatory authority, the Medical Product Agency (MPA). At the 6
regional centers that are established in Sweden, a preliminary causality
assessment is made and the data is transferred online to a database. RESULTS:
Between January 1, 1999, and June 30, 2003, 29 cases of sepsis were reported as
suspected adverse effects caused by drugs. Seventeen of these cases concerned
TNFalpha antagonists. The MPA has received 3 reports of septicemia in patients
from Northern Sweden treated with the TNFalpha antagonist etanercept. In
submitting these reports, factors that can contribute to susceptibility and to
more fatal courses of serious infections are taken into consideration.
Demographic and pharmaceutical factors as well as risks from predisposing
conditions are discussed in connection with the cases in this report. CONCLUSION:
There is a need for more information to physicians to be aware of sepsis as a
possible and serious ADR during treatment with TNF antagonists, and that patients
with predisposing diseases or those who do not regularly visit their
rheumatologist could be at higher risk.
PMID- 17043484
TI - Evidence-based soft tissue rheumatology: III: trochanteric bursitis.
AB - Trochanteric bursitis is a term used to name a syndrome that features pain and
tenderness over the greater trochanter. Present evidence suggests that in the
majority of cases, symptoms result from pathology of the gluteus medius or
minimus muscles rather than a bursa. Lower limb length discrepancy, iliotibial
band contracture, hip osteoarthritis and lumbar spondylosis are often mentioned,
but no proved as predisposing factors. After a lumbar spine or hip and other
local pathology have been considered and clinically excluded, the clinical
features of the syndrome, ie lateral location of pain plus characteristic
trochanteric tenderness are usually sufficient to reach a diagnosis. Most
patients with trochanteric bursitis can be successfully treated with a NSAID,
physiotherapy plus a local corticosteroid injection. The few refractory cases are
often treated surgically. Disappointingly, none of the therapeutic interventions
used in trochanteric bursitis have been validly assessed.
PMID- 17043485
TI - Cardiac tamponade: an uncommon presentation of hypertensive scleroderma renal
crisis.
AB - Cardiac tamponade is an extremely rare manifestation of systemic sclerosis and
has been reported to be a risk factor for the subsequent development of renal
failure. We report the case of a 37-year-old man with recently diagnosed
scleroderma who presented with chest pain and shortness of breath. He was found
to have scleroderma renal crisis as well as cardiac tamponade. He responded
hemodynamically to emergent pericardiocentesis and blood pressure control with
angiotensin-converting enzyme inhibitors. However, the renal function
deteriorated further leading to development of end-stage renal disease and
required chronic hemodialysis.Although pericardial effusions are common in
scleroderma, cardiac tamponade is rare. Coexistent hypertension and cardiac
tamponade in scleroderma have not been described previously. Elevated systemic
blood pressure can accompany and should not be used to exclude the diagnosis of
cardiac tamponade. We emphasize the importance of pericardial disease as an
uncommon but important cause of chest pain in patients with scleroderma.
PMID- 17043486
TI - Pulmonary capillaritis and hemorrhage in neonatal lupus erythematosus (NLE).
AB - We describe the case of an infant who presented to our institution with
tachypnea, cough, and hypoxemia. The baby had been diagnosed with complete heart
block (heart rate 50-60 beats/min) in utero and had a pacemaker placed at birth.
The mother was found to have both anti-Ro and anti-La antibodies. At age 3
months, the chest radiograph showed diffuse bilateral interstitial infiltrates. A
lung biopsy confirmed the presence of necrotizing capillaritis and alveolar
hemorrhage, which is an infrequent complication in pediatric patients with
systemic lupus erythematosus. The patient did well after recognition and
aggressive treatment of this previously unrecognized complication of neonatal
lupus.
PMID- 17043487
TI - Infliximab treatment of Familial Mediterranean fever and its effect on secondary
AA amyloidosis.
AB - We describe a patient with a long history of familial Mediterranean fever who
developed proteinuria as a result of secondary AA amyloidosis. In this patient,
the inflammatory process, including recurrent attacks of arthritis, abdominal
pain, nephrotic syndrome secondary to amyloidosis, and high sedimentation rate,
was rapidly suppressed by treatment with infliximab and there was remarkable
improvement of the proteinuria.Because TNF-alpha is a proinflammatory cytokine
that plays a major role in FMF and secondary amyloid, it is an appropriate target
for therapy. Our case is the first case of reactive systemic amyloidosis
secondary to familial Mediterranean fever, which responded favorably to
infliximab.
PMID- 17043488
TI - Histoplasmosis with tenosynovitis of the hand and hypercalcemia mimicking
sarcoidosis.
AB - We report on an otherwise healthy 47-year-old male who developed subacute
tenosynovitis of the hand associated with night sweats and inguinal
lymphadenopathy. He had a past history of granulomatous mediastinal lymphadenitis
with positive histoplasmosis serology 11 years previously. Carpal tunnel
exploration with biopsy demonstrated granulomatous inflammation. Granulomatous
inflammation, hypercalcemia, and an elevated serum angiotensin converting enzyme
(ACE) level suggested the diagnosis of sarcoidosis, however histoplasmosis
infection could eventually be diagnosed. This unusual presentation of
histoplasmosis underscores the fact that the diagnosis of sarcoidosis requires
careful exclusion of other causes of granulomatous inflammation, particularly
infectious agents. Even in the setting of an elevated ACE level and
hypercalcemia, the possibility of an infectious etiology must be considered
before establishing a diagnosis of sarcoidosis.
PMID- 17043489
TI - Molecular biology and immunology for clinicians 29: lipid domains, lipid rafts,
and caveolae.
AB - The development of an antigen-specific immune response depends on the peptide
loaded MHC molecule on the surface of the antigen-presenting cell being found by
the antigen-specific receptor on the cell about to be activated (the T-cell
antigen receptor for T-cells or the membrane-bound immunoglobulin molecule on B
cells). The details of this process are becoming clear now with the appreciation
of the supramolecular organization of the structures that make this cell-cell
interaction. In the last 6 years has come an appreciation of the heterogeneity of
the lipid bilayer membrane (a concept first put forth over 20 years ago), with
certain lipids and membrane-bound proteins segregating into discrete ships called
"lipid rafts" sailing in the surrounding more liquid lipid bilayer membrane.
Knowledge of these microscopic structures leads to a better understanding of how
antigen-specific responses are triggered and how aberrant responses are avoided;
as one leader in the field put it, "keeping T-cells rested but ready."Membrane
heterogeneity directly contributes to the rapid development of a more formalized
cell-cell interaction that has been termed the "immunologic synapse." It is at
this synapse that the acquired immune response, antigen specificity, is learned.
In addition to antigen presentation, lipid rafts have also been implicated in
signaling through a large number of receptors, endocytosis, cell interactions
with pathogens and toxins, budding of viruses from host cell membrane, and the
pathogenesis of prion disorders. Yet again, an insight in one discrete field of
cell biology is proving to be of great relevance in a host of other areas of
study.
PMID- 17043490
TI - Popliteal artery entrapment with peripheral thromboembolism.
PMID- 17043491
TI - Rheumatology retrospective.
PMID- 17043492
TI - 'Fibrophagia': pathophysiology and treatment.
PMID- 17043494
TI - A pathophysiologic approach to the clinical management of arthritis and pain:
current and future implications.
PMID- 17043493
TI - Is rituximab a potential new therapy in systemic sclerosis? new evidence
indicates the presence of CD20-positive B-lymphocytes in scleroderma skin.
PMID- 17043495
TI - Prostaglandins: modulators of inflammation and cardiovascular risk.
AB - Cyclooxygenase (COX)-2-specific drugs such as rofecoxib and celecoxib and the
newer agents, etoricoxib and valdecoxib, were developed to provide a safer
alternative to traditional nonsteroidal antiinflammatory drugs (tNSAIDs). These
drugs have been shown significantly to reduce endoscopically visualized
gastrointestinal ulcers, and one of them, rofecoxib, has demonstrated a 50%
reduction in clinically important gastrointestinal outcomes compared with a
tNSAID. However, COX-derived prostaglandins also have complex interactions with
the cardiovascular system. This article briefly reviews our current understanding
of the interactions between prostaglandins and cardiovascular physiology, and
addresses some of the concerns that recently have been raised regarding coxibs
and the risk of cardiovascular events.
PMID- 17043496
TI - Management strategies for osteoarthritis, ankylosing spondylitis, and gouty
arthritis.
AB - Rheumatic diseases are among the most frequent causes of pain and disability.
Effective management of rheumatic diseases including osteoarthritis (OA),
ankylosing spondylitis (AS), and gouty arthritis requires an understanding of the
underlying disease mechanisms.Symptoms of OA result from both mechanical factors
and elements of inflammation. Current management strategies target both of these
factors and generally consist of nonpharmacologic and pharmacologic
interventions, including use of nonspecific nonsteroidal antiinflammatory drugs
(NSAIDs) and cyclooxygenase-2-specific inhibitors (coxibs), which have analgesic
and antiinflammatory properties. Other approaches include intraarticular
hyaluronate and the use of alternative therapies under investigation such as
acupuncture or glucosamine.Disease mechanisms in AS involve enthesitis, an
inflammation at the site of insertion of ligaments, tendons, or joint capsules to
bone. Posture and exercise are important nonpharmacologic strategies that may be
made easier with the use of NSAIDs or coxibs. Recently developed therapies,
including tumor necrosis factor inhibitors, target the underlying disease
mechanisms and have demonstrated dramatic symptomatic effects. Disease-modifying
effects still need to be established.In gout, hyperuricemia leads to crystal
induced inflammation in some patients. Etoricoxib, one of the newer coxibs, has
shown promise in treating acute gout, with efficacy similar to indomethacin, the
current standard NSAID often used in these patients. Oral or intraarticular
steroids can also be considered. For chronic care uricosurics can be beneficial
if renal function is normal and excretion is not excessive, but allopurinol is
used most often. Nonpharmacologic modalities, such as rest and cold applications,
are useful for acute episodes, and lifestyle modification in the form of diet can
also play a role in chronic disease management.
PMID- 17043498
TI - A pathophysiologic approach to the clinical management of arthritis and pain:
current and future implications.
PMID- 17043497
TI - Pathogenesis of rheumatoid arthritis.
AB - Although widely diverse mechanisms have been held responsible for tissue damage
in rheumatoid arthritis (RA), it is likely that immune complexes are the
underlying cause. Self-aggregating complexes of 7s rheumatoid factors in synovial
fluid are a distinguishing feature of RA, whilst circulating complexes of 19s
rheumatoid factor directed against the hinge region of 7s immunoglobulins are
perhaps less specific. Other autoimmune complexes, such as those containing
antibodies directed against citrullinated peptides, have been identified and may
be more specific for RA, although the antigens against which these antibodies are
directed have not been fully characterized. Together with phagocytic cells such
as neutrophils, immune complexes are critical to the pathogenesis of RA; their
effects are mediated by a complex cascade involving complement activation and
stimulation of phagocytes via C5a and Fc receptors. These mechanisms result in a
release of mediators of inflammation and joint destruction: cytokines,
metalloproteinases, and reactive oxygen intermediates. This article will review
recent, and some not too recent, progress made towards working out the
pathogenesis of RA.
PMID- 17043499
TI - Biologic therapies on the horizon for rheumatoid arthritis.
AB - Recent research on rheumatoid arthritis (RA) has broadened our understanding of
this disease, and mediators of the disease process have been identified as
potential therapeutic targets. A series of novel agents have been developed
specifically targeting these mediators and are collectively referred to as
biologic response modifiers or biologic agents. A number of these agents have
been introduced into clinical practice or are currently in clinical trials.
Agents that have been approved include 2 monoclonal antibodies and a receptor
fusion protein, all of which target tumor necrosis factor (TNF), as well as an
inhibitor of interleukin-1 (IL-1). Other areas that are currently being
investigated are new methods of blocking TNF and other cytokines, including IL-1
and IL-6. Emerging data also suggest that both T and B cells have critical roles
in the pathogenesis of RA and could provide rational targets for therapy.
Additionally, the role of adhesion molecules in RA continues to expand, and
several agents have been proposed as potential therapies. These rapid advances in
our understanding of RA and their implications for rationally targeted therapies
are reviewed.
PMID- 17043500
TI - JCR Journal Supplement CME Questions.
PMID- 17043501
TI - Activity evaluation.
PMID- 17043502
TI - Faculty evaluation/request for credit.
PMID- 17043503
TI - Mechanisms of inflammatory pain: therapeutic implications.
AB - The study and treatment of clinical pain has historically identified particular
pain syndromes and linked their etiology with disease factors. Missing in this
approach is consideration of the mechanisms accounting for the pain that is
experienced by the patient. The recent increase in our understanding of how
peripheral and central mechanisms contribute to the perception of pain, including
the identified role of prostaglandins, has led to a shift in treatment strategy
to directly target these mechanisms. This article provides a brief overview of
pain mechanisms, focusing on inflammatory pain, and discusses the role of
cyclooxygenase (COX)-2 inhibitors as analgesic agents.
PMID- 17043504
TI - Informed choices in anti-inflammatory drug therapy: why patient risk matters.
PMID- 17043505
TI - Infliximab Therapy for Patients With Active and Refractory Spondyloarthropathies
at the Dose of 3 mg/kg: A 20-Month Open Treatment.
AB - BACKGROUND: : Infliximab at the dose of 5 mg/kg per infusion has been shown
effective for the treatment of active spondyloarthropathies. It is not clear if
the 5 mg/kg is required in most patients. OBJECTIVE: : To evaluate the long-term
efficacy and safety of infliximab at the lower dose of 3 mg/kg in patients with
active and refractory ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
METHODS: : Thirty patients were enrolled in a 78-week, single-center,
prospective, open-label pilot study, including 16 patients with severe and active
AS and 14 patients with active and refractory PsA. Infliximab (3 mg/kg, in
combination with a stable dose of methotrexate was administered intravenously at
0, 2 and 6 weeks, and q8 weeks thereafter (schedule-A) and the improvement of
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; for AS patients) and
Patient Global Assessment of Disease Activity (PDA; for PsA patients) was
monitored at baseline and at every visit (primary variables). Patients who did
not respond sufficiently at 14 weeks, as well as patients who relapsed at any
time during follow-up, received infliximab every 4 weeks (treatment schedule-B).
Three different statistical approaches (per-protocol, last observation carried
forward and by intention-to-treat) were applied. RESULTS: : Ten patients
discontinued treatment for various reasons, including 3 (10.0%) because of
allergic reactions. Twenty patients (66.7%, 9 with AS and 11 with PsA) had
completed 78 weeks of treatment (schedule-A, 11 patients; schedule-B, 9
patients). Of these patients, 18 (90.0%) showed optimal response (improvement
>/=50%), including 13 (65.0%) with improvement >/=70%. ASsessments in AS (ASAS)
50% was attained by 7/9 AS patients (77.8%). At 78 weeks of treatment,
statistically significant improvement of indices of disease activity, function
and quality of life was observed by all statistical approaches applied.
CONCLUSIONS: : Infliximab at 3 mg/kg every 8 weeks or, if needed, every 4 weeks
appears to be an effective and rather safe treatment of patients with active and
refractory AS and PsA after 78 weeks of treatment.
PMID- 17043506
TI - Successful Treatment of Dry Mouth and Dry Eye Symptoms in Sjogren's Syndrome
Patients With Oral Pilocarpine: A Randomized, Placebo-Controlled, Dose-Adjustment
Study.
AB - BACKGROUND: : Sjogren's syndrome is characterized by the presence of xerostomia
and/or xerophthalmia. Pilocarpine, a muscarinic cholinergic agonist, has been
proven to be efficacious in treating radiation-induced xerostomia (up to 30
mg/day) and symptoms of dry mouth in Sjogren's patients (up to 20 mg/day).
OBJECTIVE: : To compare the safety and efficacy of oral pilocarpine (dose
adjusted) versus placebo in the treatment of dry eye and dry mouth symptoms in
Sjogren's syndrome at 6 and 12 weeks. METHODS: : In this 11-center, 256-patient
placebo-controlled study, the safety and efficacy of oral pilocarpine (20 mg to
30 mg daily) for relief of Sjogren's-related dry mouth and dry eye symptoms was
assessed. Changes in symptoms and salivary flow were measured over 12 weeks.
RESULTS: : Compared with placebo, salivary flow was significantly increased in
the pilocarpine group (P= 0.0001) after the first dose and throughout the
study. Significant improvement in patients' global assessment of dry mouth (P=
0.0001) with relief in 5 of 7 separate oral symptoms (P= 0.02) was reported by
the treated patients throughout study. Minimal differences in 3 of 8 ocular
symptoms were noted at 6 weeks (5-mg dose), but at 12 weeks (5- to 7.5-mg dose),
the pilocarpine group demonstrated both significant improvement in global
assessment of dry eyes (P= 0.0001) and relief in 6 of 8 related symptoms (P=
0.04). The drug was well tolerated at both doses. The most common pilocarpine
related side effects were sweating, urinary frequency, flushing, and chills.
CONCLUSIONS: : Significant relief in dry mouth symptoms was noted at 20 mg/day,
and significant relief in ocular symptoms, including lower artificial tear
requirement, was noted after the dose was increased to 30 mg/day.
PMID- 17043507
TI - Risk of Upper Gastrointestinal Injury and Events in Patients Treated With
Cyclooxygenase (COX)-1/COX-2 Nonsteroidal Antiinflammatory Drugs (NSAIDs), COX-2
Selective NSAIDs, and Gastroprotective Cotherapy: An Appraisal of the Literature.
AB - Numerous studies using varying methodologies and outcome measures have examined
the gastrointestinal risks of aspirin and nonaspirin nonsteroidal
antiinflammatory drug (NSAID) use. Despite the large volume of literature,
clarity regarding the key risk factors and their quantitative importance is
lacking. We performed a comprehensive review of the literature to summarize the
incidence of gastrointestinal injury in populations with varying risk
characteristics using agents that inhibit both isoforms of cyclooxygenase and
those that selectively inhibit only cyclooxygenase-2 (COX-2).Although risk
estimates vary, the risk of serious gastrointestinal complications in NSAID users
is approximately 2.5 to 4.5 times that of nonusers. The risk of NSAID-related
gastrointestinal bleeding is augmented by concomitant low-dose aspirin and could
approach double the risk of NSAID use alone. The preponderance of evidence shows
that the risk of NSAID-related gastrointestinal bleeding is reduced approximately
50% with a coxib as compared with traditional NSAID. The relative risk of
hospitalization resulting from upper gastrointestinal bleeding for patients
treated with a nonselective NSAID was 4.4 (95% confidence interval [CI], 2.3-8.5)
and 1.9 (95% CI, 1.0-3.5) when compared with celecoxib and rofecoxib,
respectively. Aspirin increases the risk of NSAID-related gastrointestinal
bleeding in patients taking COX-2 selective inhibitors, with odds ratios ranging
from 5.8 to 7.7; however, it is unknown whether this risk is greater than the
risk from aspirin alone. The risks from both traditional NSAIDs and COX-2
inhibitors are increased in the elderly, patients on anticoagulation, and
patients with prior gastrointestinal events.Gastroprotective agents have been
found to significantly reduce the risk for gastrointestinal injury in patients
receiving NSAID therapy, especially those receiving concurrent low-dose
cardioprotective doses of aspirin. Proton pump inhibitors (PPIs) and misoprostol
both reduce the incidence of gastric and duodenal ulcers, as well as recurrence
of ulcer complications in patients receiving NSAIDs. The relative risk for
gastric ulcers ranged from 0.17 to 0.38, whereas for duodenal ulcers, the range
was 0.11 to 0.28. Although misoprostol is slightly more effective in preventing
gastric ulcers in these patients, PPIs are better tolerated. Although NSAIDs
appear safe in "low-risk" populations, our review suggests that the use of
gastroprotective cotherapy should be considered in patients at higher risk of
NSAID-related upper gastrointestinal bleeding.
PMID- 17043508
TI - Dosing of antirheumatic drugs in renal disease and dialysis.
AB - Many patients with rheumatic diseases have their management complicated by renal
problems. Renal failure modifies the metabolism of many drugs, especially by
retention. Questions often arise about the effects of renal failure on the
handling of drugs commonly used in rheumatology. For which drugs must we be
especially concerned about increased toxicity? Patients on chronic dialysis may
also need a variety of drugs for rheumatic disease. How are our drugs dialyzed,
and which of these can be safety used and how best to use them?Decisions about
dosing of rheumatic drugs are often required for the patients with chronic renal
insufficiency or on long-term dialysis, although many drugs have not been
formally studied in these settings. Patients with renal insufficiency are
excluded from most drug trials. Data for some of these drugs have to be
extrapolated based on the information available about the pharmacokinetics of the
drug.This review addresses dosing of commonly used drugs in rheumatology in
patients with chronic renal insufficiency or failure. It is compiled from a
MEDLINE search of papers dealing with renal handling of antirheumatic drugs and
suggestions for dose adjustments for these drugs. Drugs reviewed include commonly
used disease-modifying antirheumatic drugs (DMARDS), drugs used for treatment of
gout, commonly used nonsteroidal antnflammatory drugs (NSAIDS) and the newer COX
2 inhibitors.
PMID- 17043509
TI - Evidence-Based Soft Tissue Rheumatology IV: Anserine Bursitis.
AB - Anserine bursitis is a frequent cause of medial knee pain. Despite its name, the
structure at fault causing the symptoms remains unknown. Diabetes mellitus is a
known predisposing factor leading to the condition. Overweight and knee
osteoarthritis are possible additional risk factors, but their role has yet to be
assessed. Anserine bursitis is diagnosed clinically based on medial knee pain and
localized tenderness at the inferomedial knee. Current treatment of anserine
bursitis includes nonsteroidal anti-inflammatory dugs, physiotherapy, and local
glucocorticoid injections. Of these, only the latter has been shown effective in
clinical trials. Knowledge gaps in the epidemiology, pathology, and pathogenesis
of anserine bursitis should lead to additional research efforts on this common
and perplexing condition.
PMID- 17043510
TI - Spontaneous pneumothorax in scleroderma.
AB - We present an illustrative case of a patient with advanced scleroderma who
presented with a spontaneous pneumothorax, a condition that has only rarely been
reported previously in association with scleroderma. Our patient and those
previously reported had advanced pulmonary fibrosis with honeycombing and
subpleural cysts, with spontaneous pneumothorax occurring secondary to cyst
rupture. Our patient was treated with chest tube thoracostomy, but her
spontaneous pneumothorax later recurred. She was then treated with talc
pleurodesis and has not had a recurrence in 18 months of follow-up.Spontaneous
pneumothorax remains a rare pulmonary manifestation of scleroderma, occurring
only in patients with advanced pulmonary fibrosis associated with cyst formation
and rupture. Initial management consists of chest tube insertion, but recurrence
is high and may require pleurodesis or partial lobectomy. Physicians managing
patients with scleroderma should be aware of spontaneous pneumothorax, especially
in those with advanced pulmonary fibrosis and subpleural cysts.
PMID- 17043511
TI - Polyarteritis nodosa complicated by catastrophic antiphospholipid syndrome.
AB - Polyarteritis nodosa (PAN) is a vasculitis of small- and medium-sized vessels,
characterized by vascular aneurysms that can lead to ischemia and infarction. We
present the case of a patient with classic polyarteritis nodosa in abdominal
organs who additionally demonstrated antitreponemal and antiphospholipid
antibodies, resulting in a severe cerebral thrombosis. This case highlights: 1.
The potential for false-positive syphilis serology in PAN patients, and 2. The
rare coexistence of polyarteritis nodosa and the catastrophic antiphospholipid
syndrome.
PMID- 17043512
TI - Avascular necrosis of bone associated with primary antiphospholipid syndrome:
case report and literature review.
AB - We describe, the case of a 34-year-old mestizo Mexican woman with previous
history of fetal loss, deep vein thrombosis that developed avascular necrosis
(AVN) of the right knee with strong positive levels of anticardiolipin antibodies
(aCL) IgG and IgM. AVN of bone in association with aCL has been seen principally
in systemic lupus erythematosus patients. However, few cases have been reported
of AVN as a clinical manifestation of primary antiphospholipid syndrome. A review
of the association of aCL and AVN in patients with systemic lupus erythematosus,
primary antiphospholipid syndrome, and idiopathic osteonecrosis is presented.
PMID- 17043513
TI - Treatment of resistant adult still disease with infliximab: a report of 2 cases.
AB - Adult Still disease is characterized by high fever, arthritis, leukocytosis,
hepatosplenomegaly, rash, and lymphadenopathy. It affects primarily young adults
and is often disabling or even fatal. Many patients achieve long-term remissions,
while others may develop a chronic illness refractory to multiple therapies.
Polyarthritis or root joint involvement has been identified as a marker of
chronic disease. No controlled studies on second-line agents have been published,
but anecdotal studies suggest efficacy of a variety of agents including
hydroxychloroquine, sulfasalazine, penicillamine, and methotrexate. Although
these therapies have been used, optimal treatment of patients with resistant
disease remains problematic. High levels of tumor necrosis factor have been
noted, and recent report indicates etanercept may be an effective therapy. We
report 2 cases of adult-onset Still disease resistant to NSAIDs, steroids, and
methotrexate that have been successfully maintained on 5 mg/kg infliximab for 30
and 29 months, respectively, with improvement of signs and symptoms despite a
reduction of steroid dosage. In patients with resistant disease, infliximab may
be a safe, effective agent. Its use in this disease merits further study.
PMID- 17043515
TI - Thomas sydenham (1624-1689), on gout: 1717.
PMID- 17043514
TI - Basic science for the clinician 28: T-helper cell subtypes.
AB - The immune response is finely tuned to the various invaders that may cause damage
and disease. There is an innate immune system and an acquired immune response,
but there is much overlap and recruitment across these lines of demarcation.
Broadly speaking, there are cellular immune responses (cellular effectors that
identify intracellular pathogens and damage and kill the affected cell) and
humoral (B cells become plasma cells which make antibodies to bind extracellular
pathogens and their products) that draw upon both systems. At the pivotal point,
where decisions are made whether to mount a primarily cellular or a humoral
response are T-helper cells (CD4). As you may have read, CD4 cells come in at
least 2 subtypes: TH1 cells predispose to the development of a primarily cellular
responses and TH2 predispose to humoral responses. Not very complicated, but
worthy of some discussion to look at the cytokines produced, the changes these
cytokines evince, and how the balances (dare I say yin and yang) keep us healthy
but also may get us into trouble!
PMID- 17043516
TI - Fever therapy for arthritis.
PMID- 17043517
TI - Bradycardia due to Methylprednisolone Therapy.
PMID- 17043518
TI - An Ayurvedic-derived osteoarthritis treatment - what can this teach us?
PMID- 17043519
TI - Scleroderma renal crisis: the sword of damocles.
PMID- 17043520
TI - A 32-week randomized, placebo-controlled clinical evaluation of RA-11, an
Ayurvedic drug, on osteoarthritis of the knees.
AB - BACKGROUND: The ancient Indian (Asian) Ayurvedic medicinal system uses
herbomineral drugs to treat arthritis. Despite centuries of use, very few have
been tested by drug trials. RA-11 (ARTREX, MENDAR), a standardized multiplant
Ayurvedic drug (Withania somnifera, Boswellia serrata, Zingiber officinale, and
Curcuma longa) is currently used to treat arthritis. OBJECTIVE: The objective of
this study was to evaluate the efficacy and safety of RA-11 in patients with
symptomatic osteoarthritis (OA) of the knees. METHODS: A total of 358 patients
with chronic knee pain were screened free-of-cost in "arthritis camps" in an
Indian metropolis. Ninety patients with primary OA of the knees (ACR
classification; Arthritis Rheum 1986;29:1039-1049) were found eligible
(postanalgesic washout pain visual analog score [VAS] > or =40 mm in either or
both knees on body weight-bearing activities) to enroll into a randomized, double
blind, placebo-controlled, parallel efficacy, single-center, 32-week drug trial
(80% power to detect 25% difference, P = 0.05, 2-sided). Concurrent
analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not
allowed. Lifestyle and/or dietary restrictions, as per routine Ayurveda
practices, were not imposed. Pain VAS (maximum pain in each knee recorded by the
patient during the preceding 48 hours) and modified WOMAC (Western Ontario
McMaster University OA Index, Likert scale, version 3.0) were the primary
efficacy variables. The WOMAC section on "physical function difficulty" was
modified for Indian use and validated before the trial. Routine laboratory
testing was primarily done to monitor drug safety. At baseline, the groups
(active = 45, placebo = 45) were well matched for several measures (mean pain
VAS: active = 6.17; placebo = 6.5). RESULTS: 1) EFFICACY: Compared with placebo,
the mean reduction in pain VAS at week 16 (active = 2.7, placebo = 1.3) and week
32 (active = 2.8, placebo = 1.8) in the active group was significantly (P <0.05,
analysis of variance [ANOVA]) better. Similarly, the improvement in the WOMAC
scores at week 16 and week 32 were also significantly superior (P <0.01, ANOVA)
in the active group. 2) SAFETY: Both the groups reported mild adverse events (AE)
without any significant difference. 3) Withdrawals: Twenty-eight patients were
discontinued. None reported drug-related toxicity. The majority failed follow
up/compliance. No differences were observed between the groups. CONCLUSION: This
controlled drug trial demonstrates the potential efficacy and safety of RA- 11 in
the symptomatic treatment of OA knees over 32 weeks of therapy.
PMID- 17043521
TI - Effects of functional electrostimulation on pain, muscular strength, and
functional capacity in patients with osteoarthritis of the knee.
AB - BACKGROUND: Osteoarthritis (OA) of the knee is a common cause of chronic
disability in patients with quadriceps muscle weakness. Beneficial effects have
been proposed for functional electrostimulation (FES) and exercise at the muscle
level. OBJECTIVES: The objective of the study was to begin to compare the effects
of both therapeutic modalities on quadriceps muscle strength, pain, and
functional capacity in patients with OA of the knee and to prove whether the
combination of these modalities provides greater benefits than the use of each
therapeutic modality alone. METHODS: This pilot study included 37 patients with
OA of the knee who were assessed at baseline and at 8 weeks, accounting for the
following variables: body mass index, knee pain (measured using a VAS), WOMAC,
quadriceps strength (measured using a dynamometer) and 6-minute walk test.
Patients were randomized into 3 groups: (A) 8 patients who received FES 3 times
per week; (B) 10 patients recruited into a twice-a-week physical training
program; and (C) 8 patients under combined therapy; 29.7% of patients were lost
to follow-up due to noncompliance with the treatment plan, leaving a total of 26
patients at 8 weeks. RESULTS: Pain and WOMAC improved in all 3 groups; strength
improved significantly in the exercise-only group; the FES + exercise combination
improved strength significantly when compared with the individual therapeutic
procedures. CONCLUSIONS: FES merits a larger placebo-controlled study as it may
prove to be useful patients with OA of the knee; the combination with exercise
was helpful in improving muscle strength. This technique may be considered in
patients who are unable to carry out physical activity due to health problems or
in those who are not interested in physical activity.
PMID- 17043522
TI - Total joint fluid urate in gout.
AB - BACKGROUND: Synovial fluid urates are traditionally measured as supernatants, and
levels are reported to be comparable to serum levels. OBJECTIVE: We have decided
to attempt to define a more accurate parameter of gouty urate load in the joint
fluid. METHODS: In 23 gouty joints of various activity, the urate level was
determined by both the traditional method and by heating and agitation to
dissolve crystals yielding total joint fluid urate (TJFU). RESULTS: TJFU was
higher than the serum level or traditional urate level, and the gradient (TJFU
synovial fluid urate) was proportional to gouty activity. CONCLUSIONS: We propose
that TJFU is more representative of the pathophysiology of gout and deserves
further evaluation of its implications.
PMID- 17043523
TI - Preoperative autologous blood donation by arthritis patients is associated with
preoperative anemia and perioperative transfusion.
AB - BACKGROUND: Preoperative autologous blood donation (PAD) became a common practice
in the 1990s in an attempt to reduce the risk of transmission of infectious
agents from allogeneic blood. However, a potential risk of PAD is the development
of preoperative anemia that may lead, in turn, to an enhanced need for
transfusion. Furthermore, the ready availability of autologous blood may
predispose to more liberal transfusion peri-/postoperatively. OBJECTIVES: To
examine these hypotheses, we retrospectively examined a cohort of knee and hip
arthroplasty patients. METHODS: Charts of patients of 2 orthopedic surgeons from
the mid 1980s and 1990s were reviewed for transfusions needed and hematocrits
before and after arthroplasties. RESULTS: PAD proved to be a significant risk
factor for the development of preoperative anemia and for peri-/postoperative
blood transfusion even after adjusting for confounders. CONCLUSIONS: These
results suggest that PAD may lead to a self-defeating cycle of blood donation
followed by blood transfusion. With the improved safety of the allogeneic blood
supply, rheumatologists may want to play a more active role in considering PAD in
patients in whom elective arthroplasty is planned.
PMID- 17043524
TI - Evidence-based soft tissue rheumatology. V: plantar talalgia.
AB - Present evidence indicates that the main cause of plantar talalgia (PT) is a
noninflammatory derangement at the proximal insertion of the plantar fascia. In
athletes, predisposing ankle and rear-foot biomechanical abnormalities have been
identified; in nonathletes, risk factors for the condition remain controversial.
PT diagnosis is largely clinical, the key findings being pain and tenderness on
the plantar aspect of the rear foot. Ultrasonography is a reliable confirmatory
study in doubtful cases. Therapies in PT include nonsteroidal anti-inflammatory
drugs, orthotic devices, night ankle dorsiflexion splints, physiotherapy, local
glucocorticoid, and extracorporeal shockwave therapy. In recalcitrant cases,
surgery may be offered. Of these therapies, only local glucocorticoid, as
delivered by injection or iontophoresis, has shown short-term efficacy in
controlled trials. The efficacy of ankle dorsiflexion splints and extracorporeal
shockwave therapy is still controversial. Thus, important knowledge gaps remain
on etiology, diagnosis, and treatment of PT.
PMID- 17043525
TI - Vasculitis of the female genital tract.
PMID- 17043526
TI - Cauda Equina Syndrome as a Clinical Presentation of Primary Angiitis of the
Central Nervous System (PACNS).
AB - Primary angiitis of the central nervous system (PACNS) is a form of vasculitis
affecting the central nervous system (CNS) that is not associated with systemic
disease or vasculitis outside the CNS. It is a rare disease with significant
morbidity and mortality. Delay in diagnosis and treatment is common due to its
nonspecific clinical symptoms and lack of efficient noninvasive diagnostic tests.
The finding of vasculitis in the leptomeningeal and cortical biopsy sample has
remained the gold standard for making the diagnosis of PACNS. We describe a
patient whose clinical symptoms of cauda equina syndrome led to a nerve root
biopsy that was consistent with PACNS despite prior extensive investigations
including a brain biopsy. This report highlights the cauda equina syndrome as a
clinical presentation of PACNS and emphasizes the need for awareness of this rare
condition.
PMID- 17043527
TI - Fracture complicating the bone marrow edema syndrome.
AB - Bone marrow edema syndrome (BMES), also known as transient regional osteoporosis,
is a rare and poorly understood disease process. We present a case of an elderly
patient with the BMES who had a relapsing and remitting course complicated by a
hip fracture which presented the unique and a previously unreported opportunity
to examine the bony architecture pathologically. The patient responded well to
calcitonin and bisphosphonate therapy after surgical repair of his fracture.This
case highlights an underappreciated potential complication of BMES. Though not
previously reported in the literature, BMES may be associated with active
osteoporotic changes, with an infrequent risk of fracture that may be amenable to
potential therapeutic interventions. Pathologically, BMES may represent a
spectrum of disease consisting of an osteoclast-rich phase (transient regional
osteoporosis phase) predisposing to fracture in addition to the more indolent
osteoclast-poor phase with bone marrow edema more commonly associated with the
disease. We hypothesize that it is the osteoclastic-rich phase which may benefit
from early introduction of weight bearing activities, calcitonin,
bisphosphonates, or parathyroid hormone. For example, bisphosphonates reduce bone
resorption directly. Indirectly, bisphosphonates may also increase osteoblast
differentiation and number and thus improve bone quality, an added benefit in the
treatment of bone involved in the BMES, whether in the osteoclast-rich or
osteoclast-poor phase.Further study should evaluate this osteoclastic-rich phase,
which may be a transient pathologic phenomenon and which has not been described
previously. Transient regional osteoporosis, therefore, may represent one point
in the spectrum of the BMES. Hence, we would argue that BMES is a more accurate
name for the full spectrum of this disease entity.
PMID- 17043529
TI - Thomas Sydenham (1624-1689), on Scorbutical Rheumatism: 1717.
PMID- 17043528
TI - Scleroderma renal crisis following widespread application of topical
triamcinolone.
AB - A 52-year-old patient with early diffuse scleroderma (Scl) developed scleroderma
renal crisis (SRC) following exposure to topical steroid cream. She had applied a
larger-than-prescribed quantity of triamcinolone acetonide 0.1% cream all over
her body for 3 months, the absorption of the cream being the equivalent of 7.5 mg
of oral prednisone per day. Her SRC was subsequently managed successfully with
aggressive antihypertensive therapy and hemodialysis, and she was discharged
home. High-dose corticosteroids (CS) have long been implicated in the development
of SRC, but topical and low-dose CS until now have not. In our opinion, low-dose
CS and a predisposing clinical setting appeared sufficient to provoke SRC and may
broaden the proscription against CS in Scl.
PMID- 17043530
TI - Basic science for the clinician 31: CD molecules of relevance to immunity,
inflammation, and rheumatologic syndromes.
AB - Molecular biologic technology has allowed us to study some of the many proteins
expressed by leukocytes at different stages of differentiation, activation, and
proliferation. Being able to purify cells with 1 or more surface molecules (eg,
by FACS or lysis) with monoclonal antibodies and complement and identifying
changes as cells are stimulated or activated has given us real insights into what
is happening and how we might be able to modify cells that are going astray (eg,
malignancy, autoimmunity). Over the years, there has been remarkable cooperation
between laboratories to bring order out of chaos; by trading reagents, scientists
have been able to identify the molecules being identified by different
laboratories and come up with standardized names, often within the CD, or
"clusters of differentiation," framework. These names are not acronyms, and the
function and role of the molecule bearing a certain CD designation is not
apparent. Worse, the proliferation of numbered CD molecules (over 250, with more
to come after another conference in 2004) makes interpretation of the literature
very difficult for those not immersed in the field. Thus, I have chosen (nearly
arbitrarily and often based on my own interests) a number of CD molecules to
briefly describe, pointing out the clinical relevance of each. It is worth
reflecting on the fact that many of these were discussed in previous
contributions to this series (as is pointed out in the following article). For
those of you with the fortitude to follow this series, see how far you (and all
of science) have come!
PMID- 17043531
TI - Railway spine, posttraumatic fibromyalgia, and junk science in the courtroom (ca.
1975).
PMID- 17043532
TI - Failure to identify Salmonella bacteria DNA by polymerase chain reaction in
peripheral blood and synovial fluid cells in chinese patients with rheumatoid
arthritis and ankylosing spondylitis.
PMID- 17043533
TI - Is primary biliary cirrhosis another example of an immune-mediated complication
of klinefelter syndrome?
PMID- 17043534
TI - Porphyria cutanea tarda and scleroderma.
PMID- 17043535
TI - Lupus nephritis outcome with and without renal biopsy: a 5-year comparative
study.
AB - BACKGROUND: : Renal biopsy is an important tool in devising an adequate treatment
plan for lupus nephritis. However, it is not always possible to perform a biopsy,
and in many cases, treatment must rely exclusively on clinical data. OBJECTIVE: :
The aim of this study was to compare the 5-year course of patients treated
without a biopsy with another group with histologic evidence of diffuse
proliferative glomerulonephritis (DPGN). METHODS: : The no-biopsy group consisted
of 30 patients with lupus with strong clinical and laboratory suspicion of
proliferative glomerulonephritis in whom a renal biopsy was unavailable either
because of medical contraindication or the patient's refusal. The biopsy group
included 30 patients undergoing biopsy and a histologic diagnosis of DPGN.
Patients were followed from the onset of nephritis and at 18, 36, and 60 months.
RESULTS: : At onset, the no-biopsy group showed lower C3 levels and higher
proteinuria, although both groups showed evident deterioration of the renal
function. No significant differences were found in treatment, outcome, survival,
renal function tests, or in the development of kidney failure. CONCLUSIONS: :
Proliferative glomerulonephritis deserves prompt diagnosis and treatment. This
study demonstrates that experience in the management of lupus nephropathy,
together with clinical and laboratory data, are often enough information to
adequately treat proliferative glomerulonephritis even in the absence of a renal
biopsy.
PMID- 17043536
TI - Does transcutaneous electrical nerve stimulation improve the physical performance
of people with knee osteoarthritis?
AB - BACKGROUND: : According to a recent metaanalysis study, there is strong evidence
to support the view that transcutaneous electrical nerve stimulation (TENS) is an
effective treatment for managing osteoarthritis (OA) knee pain. However, there is
limited evidence showing its effectiveness in improving physical function. This
study examined whether TENS alone can improve physical function in terms of range
of knee motion and the Timed-Up-and-Go Test. METHODS: : Subjects were randomly
allocated into 2 groups receiving TENS at 100 Hz or a placebo TENS. Outcome
measures included: 1) visual analog scale for measuring the intensity of the
present pain, 2) Timed-Up-and-Go Test, and 3) range of knee motion (ROM).
Repeated-measures analysis of variance and Pearson correlation were used for data
analyses. RESULTS: : By day 10, TENS produced a significantly greater increase in
maximum knee ROM than the placebo group (P = 0.033). TENS also significantly
increased the pain-limited knee ROM across sessions, but the between-group
difference was short of significance (P = 0.067). The decrease in time in
performing the Timed-Up-and-Go Test was also not significantly different between
the 2 groups. A moderate correlation was observed between the reduction in pain
scores and the improvement in the Timed-Up-and-Go Test. CONCLUSIONS: : Our
findings suggested that TENS did improve some of the physical parameters but over
10 days was unable to produce significant improvement in functional performance
among people with knee OA. A larger-scale study with the assessment of other
functional outcomes may be required to clarify if TENS could improve function in
people with knee OA. Also, exercise can be considered to be an important adjunct
treatment to TENS to improve function significantly.
PMID- 17043537
TI - Brucellar spondylitis: review of 25 cases.
AB - OBJECTIVE: : Brucellar spondylitis is one of the most serious complications of
brucellosis. It should be considered in patients who have back pain and
neurologic disorders as well as systemic symptoms and findings in or from endemic
areas such as Turkey. This report describes important features of the disease.
METHODS: : Twenty-five patients with brucellar spondylitis were retrospectively
evaluated in terms of their clinical, laboratory, and radiologic features and
their response to different treatment regimens. RESULTS: : The most common
symptoms of brucellar spondylitis were back pain, fever, and sweating. Rose
Bengal tests were positive in all of these patients. Brucella species was
isolated from blood cultures of 8 (32%) patients. Magnetic resonance imaging
(MRI) showed that the lumbar segment was the most frequently involved region.
Different combination regimens including 2 or 3 antibiotics were used.
Combination of tetracycline (especially doxycycline) and streptomycin was the
most widely used therapy regimen. Trimethoprim-sulfamethoxazole, ciprofloxacin,
ofloxacin, and rifampin were also included in some combination therapies. In this
series, the mean duration of antimicrobial therapy was 130 +/- 45.6 days (range,
77-281 days), and 92% of patients received therapy for >/= 90 days. There were no
mortalities in this study. CONCLUSIONS: : Brucellar spondylitis should be
considered in patients with back pain and neurologic disorders as well as
systemic symptoms and findings in endemic areas. MR imaging is recommended in
suspected cases. The patients can be treated effectively treated with appropriate
antibiotic combinations. Follow up is important because relapses can occur.
PMID- 17043538
TI - Prevalence of comorbid conditions and prescription medication use among patients
with gout and hyperuricemia in a managed care setting.
AB - BACKGROUND: : Comorbid disorders and multiple prescription drug use are common
among patients with gout and/or hyperuricemia and may influence the clinical
course and outcome of gout. OBJECTIVE: : We wanted to document the conditions and
associated medications in a large group of patients with gout in a managed care
setting. METHODS: : This study was a 2-year, retrospective, administrative claims
analysis examining comorbid conditions and medication use among managed care
enrollees with gout/hyperuricemia across the United States. RESULTS: : Of the
9482 study subjects (82.1% men, mean age 52 years), 57.9% had hypertension, 45.3%
had a lipid disorder, 32.5% had both conditions, and 19.9% had diabetes mellitus.
During the 24-month follow-up period, subjects had 5 +/- 3.14 (mean +/- standard
deviation) different comorbid conditions and filled prescriptions for of 11.0 +/-
7.90 different medications. The most commonly filled prescriptions included
antihypertensive drugs, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
inhibitors (statins), and nonsteroidal antiinflammatory drugs (NSAIDs).
CONCLUSIONS: : The study indicates a high prevalence of both comorbid conditions
and multiple medication use among managed care enrollees with gout and/or
hyperuricemia. Heightened awareness of these associated disorders is important
because they may warrant treatment of their own accord and often some
modification of gout management. Drugs, particularly diuretics and prophylactic
aspirin, could potentially contribute to the development of hyperuricemia and
gout.
PMID- 17043539
TI - Can a nurse-directed intervention reduce the exposure of patients with knee
osteoarthritis to nonsteroidal antiinflammatory drugs?
AB - OBJECTIVE: : The objective of this study was to evaluate a nurse-directed self
management intervention for managed care patients with knee osteoarthritis (OA),
emphasizing nonpharmacologic (NonPharm) management of pain and functional
impairments and minimization of exposure to the risks and costs of nonsteroidal
antiinflammatory drugs (NSAIDs). METHODS: : Subjects were 186 patients from a
large health maintenance organization (HMO) who satisfied American College of
Rheumatology clinical criteria for knee OA. Two of 4 HMO sites (and their patient
cohorts) were randomly assigned to the education group; the other 2 served as a
delayed-intervention control group. At each location of care for the education
group, an arthritis nurse educator, in consultation with the patient's primary
care physician (PCP), followed a detailed algorithm for implementing and
monitoring the response to NonPharm treatment modalities (eg, quadriceps
strengthening exercises, counseling in principles of joint protection, use of
thermal modalities). The nurses apprised the PCP of the patient's progress and
made algorithm-based recommendations, as appropriate, for reduction of dose, and
eventual discontinuation, of NSAIDs in favor of acetaminophen. Outcomes (measured
at baseline, 3, 6, and 12 months) included pain and function scales from the
Western Ontario and McMaster Universities (WOMAC) OA Index. RESULTS: : The
treatment groups were similar at baseline with respect to sociodemographic and
clinical characteristics. Medical record audits revealed that NonPharm treatments
(most often exercise) were implemented by 75% of patients in the education group
but by only 18% of patients receiving routine care (P < 0.00001). Over the
subsequent 12 months, 20 patients (26%) in the education group, but only 3 (5%)
in the control group (P = 0.002), underwent changes in drug treatment of OA pain
consistent with the NSAID-sparing goals of the intervention, ie, acetaminophen as
initial drug of choice; reduction in dose, or discontinuation, of NSAID; switch
from an NSAID to an analgesic. Only one patient in the education group required
reinstitution of NSAIDs because of an increase in knee pain. Mean WOMAC scores
indicated no deterioration of pain control or function over 12 months in the
group treated according to the algorithm. CONCLUSION: : Incorporation into the
primary care setting of self-care education for patients with knee OA, with
collaboration between a proactive arthritis nurse and the patient's PCP, can
reduce reliance on NSAIDs without a resultant increase in OA pain and disability.
PMID- 17043540
TI - The prevalence of fibromyalgia in collegiate athletes.
AB - BACKGROUND: : The prevalence of fibromyalgia in the general population is
reported in numbers that range between 0.5% and 10%, with considerable
variability in the populations studied and criteria for diagnosis used. The
prevalence in competitive young adult athletes is unknown, but we expect it to be
less than the general population. OBJECTIVES: : The objective of this study was
to determine the prevalence of fibromyalgia in college student athletes. METHODS:
: We conducted a prospective, cross-section cohort evaluation of 641 athletes
using the 1990 American College of Rheumatology (ACR) criteria. Volunteer college
student athletes were evaluated with a questionnaire and physical examination at
preparticipation physical examinations from 1993 to 1999. RESULTS: : Of the 641
athletes examined, we found only one who met the ACR criteria for a diagnosis of
fibromyalgia. LIMITATIONS: : There were a limited number of athletes involved,
there was no age- or activity-matched control group, and there were no other
demographic information or associated symptoms collected. CONCLUSIONS: : The
prevalence for fibromyalgia in this population was found to be 0.16%, which is
lower than the prevalence found in studies describing other populations. The
protective effects of this population are unclear but could be related to age,
fitness level, self-selection, and/or other factors.
PMID- 17043541
TI - Corticosteroid therapy in an alphaviral arthritis.
AB - BACKGROUND: : Corticosteroid use during acute viral arthritis is considered to be
contraindicated as a result of the risk of immunosuppression causing enhanced
infection and disease exacerbation. OBJECTIVES: : The objective of this study was
to analyze the effect of oral corticosteroid therapy on symptoms of the viral
arthritic disease, Ross River virus disease (RRVD). METHODS: : Patients with RRVD
were enrolled in 2 prospective longitudinal studies. Medications and
comorbidities were recorded and the patients' health was assessed using 2
validated quality-of life-questionnaires, the Comparison of Clinical Health
Assessment Questionnaire (CLINHAQ) and the Medical Outcomes Study Short Form (SF
36). RESULTS: : Six patients taking corticosteroids showed no exacerbation of
RRVD compared with patients not taking steroids. The CLINHAQ Functional
Disability Index also indicated that corticosteroid users recovered faster
compared with patients using nonsteroidal antiinflammatory drugs. CONCLUSION: :
Conventional concern that corticosteroid treatment will exacerbate disease
appears unjustified for alphaviral arthritides once serodiagnosis has
demonstrated antiviral immunity.
PMID- 17043542
TI - Refractory sweet syndrome with autoimmune organizing pneumonia treated with
monoclonal antibodies to tumor necrosis factor.
AB - We describe a 54-year-old man with highly refractory Sweet syndrome associated
with autoimmune multifocal organizing pneumonia and underlying myelodysplastic
disorder. His lung disease responded to oral cyclophosphamide. However, his skin
disease and systemic symptoms followed a chronic course and responded only to
very high doses of corticosteroid and were refractory to a number of
corticosteroid-sparing agents. He was ultimately treated with infliximab,
resulting in remission of his cutaneous and systemic symptoms and successful
tapering of his corticosteroid dose. Subsequently, infliximab was replaced with
adalimumab to achieve more sustained remission. His pulmonary lesions have not
recurred on this treatment. His myelodysplastic syndrome followed a very slowly
progressive course consistent with refractory anemia. This case report
demonstrates the effectiveness of treatment with monoclonal antibody specific for
tumor necrosis factor alpha (TNFalpha) in a patient with severe manifestations of
Sweet syndrome refractory to other treatments.
PMID- 17043543
TI - Accelerated cutaneous nodulosis during infliximab therapy in a patient with
rheumatoid arthritis.
AB - Up to one fourth of patients with rheumatoid arthritis (RA) may have
extraarticular findings such as subcutaneous nodules. These are discrete
subcutaneous granulomatous nodules located on extensor surfaces, especially of
the elbows. Over the past 10 to 15 years, there have been reports of accelerated
cutaneous nodulosis in patients receiving methotrexate therapy. Recently,
antitumor necrosis factor alpha (anti-TNFalpha) biologic therapy has become
commonplace in the management of RA, especially in methotrexate-resistant or
toxic patients. There have been recent reports of accelerated nodulosis in
patients with RA on etanercept. We describe what we believe is the first case of
accelerated cutaneous nodulosis resulting from infliximab anti-TNFalpha therapy
in a patient with RA. One year after the initiation of infliximab, with RA in
remission, our patient noted the rapid development of rheumatoid nodules of both
hands. A biopsy was characteristic of a rheumatoid nodule, revealing palisading
granulomas and fibrinoid necrosis.
PMID- 17043544
TI - Hashimoto encephalopathy (autoimmune encephalitis).
AB - Patients with Hashimoto thyroiditis may have neurologic manifestations that have
been described in the literature for some decades now; these include psychiatric
disorders, abnormal movements, and simulation of cerebrovascular events. Nuclear
magnetic resonance (MRI) studies have revealed diffuse leukoencephalopathy in
most cases. We describe a case having clinical manifestations simulating
cerebrovascular events, together with cognitive alterations (a presentation
already described in other patients). Among the 2 main forms of neurologic
manifestations, the cognitive type, which is probably associated with
endocrinologic alteration, may improve with hormone supplement. Those alterations
simulating cerebrovascular events are most probably related to autoimmune
vasculitis. The latter may improve with the administration of corticosteroids,
which are proposed as treatment of this disorder.
PMID- 17043545
TI - Comment.
PMID- 17043546
TI - Combination therapy with montelukast and ketotifen for arthritis and rash
resulting from idiopathic hypereosinophilic syndrome.
AB - Idiopathic hypereosinophilic syndrome (IHES) is a rare condition of uncertain
etiology characterized by marked peripheral blood eosinophilia and organ system
dysfunction that cannot be explained by any factor other than the presence of
eosinophils or their potentially toxic products. Diagnostic criteria include 1) a
sustained eosinophilia greater than 1500/mm for longer than 6 months, 2) absence
of other causes of eosinophilia, including parasitic infections and allergic
diseases, and 3) multiorgan involvement (ie, lungs, heart, central nervous
system, skin, liver, joints). Steroids represent the initial therapeutic
approach, although for those patients unresponsive to steroids, cytotoxic
chemotherapy should be considered. We describe a case of IHES characterized by
polyarticular inflammatory joint involvement, hypereosinophilia, and urticarioid
skin manifestations without visceral involvement. Synovial fluid smears as well
as pathology of skin lesions and knee synovial membrane confirmed the presence of
numerous eosinophils. The patient was successfully treated with a combination
therapy of a cysteinyl leukotriene receptor antagonist (montelukast) and
ketotifen. Hypereosinophilic syndrome like in this patient is a rare cause of
polyarthritis.
PMID- 17043547
TI - Rheumatology grand rounds at rush: patient self-report data are key to better
patient care.
PMID- 17043548
TI - Jean martin charcot (1825-1893), on gout.
PMID- 17043549
TI - Crossword puzzle.
PMID- 17043550
TI - Basic science for the clinician 33: interleukins of current clinical relevance
(part I).
AB - Normal orchestration of wound healing, the protective immune response and
inflammation, involve a bewildering array of cells that communicate to each other
locally by means of cell-surface receptors and their ligands. For local and
middle- to long-distance coordination, some of these same cells make and export
soluble messengers that communicate to both immune and nonimmune cells. Although
all these messengers have a role in normal immune homeostasis, it is apparent
that many are involved in tissue damage in a variety of diseases, eg, rheumatoid
arthritis and osteoarthritis. Some of these molecules are known as interleukins.
The list of interleukins (IL) is now nearing 30 and, as a result of the molecular
biology revolution, we now know the direct clinical relevance of many of them. As
benchtop molecular biology matures into therapeutic and diagnostic tools,
clinicians must begin to master this disparate group of molecules; making this
harder is the fact that unlike acronyms (often impenetrable as they might be), an
IL designation does not give a clue as to the source, target, or action of the
IL. IL-1 and IL-2 were the first messengers to bear the "interleukin" name 25
years ago; they are well known to rheumatologists by now, so this article deals
with some of the characteristics of the other clinically relevant IL molecules
starting with IL-3.
PMID- 17043552
TI - The end of an era: a commentary on the demise of the bulletin on rheumatic
diseases (1950-2004).
PMID- 17043551
TI - Small joint monoarthritis and pyoderma gangrenosum in newly diagnosed ulcerative
colitis: an unusual presentation.
PMID- 17043553
TI - Avoiding all nonsteroidal antiinflammatory drug toxicity.
PMID- 17043555
TI - The association of smoking with vaginal flora, urinary tract infection, pelvic
floor prolapse, and post-void residual volumes.
AB - OBJECTIVE: This study examined the association of smoking with changes in vaginal
flora, the prevalence of urinary tract infection, genital prolapse, and
incomplete bladder emptying. METHODS: The authors conducted a retrospective
review of charts for 305 women. In addition to smoking habits, data on age,
parity, degree of genital prolapse, vaginal flora, urinary residual, urinary
tract infection, and hormone replacement therapy were collected and analyzed.
RESULTS: Smoking did not correlate with urinary tract infection, the amount of
post-void urine residual volumes, or pessary use. Smoking was significantly
associated with the presence of a severe degree of genital prolapse. Smoking
independently affected vaginal flora, increasing the odds of developing bacterial
vaginosis. CONCLUSION: Smoking was associated with an increased risk of
developing bacterial vaginosis and having severe genital prolapse. Smoking was
not associated with urinary tract infection or the amount of post-void residual
urine.
PMID- 17043554
TI - Endocervical sampling: a comparison of endocervical brush, endocervical curette,
and combined brush with curette techniques.
AB - OBJECTIVE: This study was conducted to compare the collection of endocervical
specimens by endocervical brush, curette, and a combined curette and brush
technique. METHODS: Women underwent colposcopy with endocervical curettage using
one of 3 collection methods. RESULTS: The endocervical brush produced equivalent
amounts of tissue and endocervical cells compared to the curette alone or
combined techniques. More squamous and glandular atypia and SIL/AIS were found
when a brush was used, but a statistically significant difference was not noted.
The brush alone produced a significantly greater percentage of samples that were
insufficient for diagnosis and more specimens without stromal components. The
brush with the curette as a combined technique provided no improvement in amounts
of tissue, endocervical cells/clusters, or amount of stroma retrieved.
CONCLUSION: Each technique has advantages and disadvantages in terms of what
types of components are collected and what diagnosis may be determined from the
sample taken.
PMID- 17043556
TI - Genital human papillomavirus types in immunocompetent and immunodepressed women
in northeast Italy: prevalence and cytomorphological correlations.
AB - OBJECTIVE: We evaluated the prevalence of genital human papillomavirus (HPV)
types in correlation with cytomorphological findings in patients at different
risk for cervical intraepithelial neoplasia living in northeast Italy. METHODS:
Exfoliated cervicovaginal cells from 943 women, who were divided into three
groups, were analyzed by polymerase chain reaction. RESULTS: Overall, HPV
prevalence rates were 7%, 38%, and 52%, respectively. The single most frequent
type was HPV 16 (18%), followed by types 6, 31, 53, 58, 61, and
novel/unidentified (5-7%); other types had a frequency <5%. Infection with
multiple types was present in 12%. In HIV-infected women, HPV infection was
correlated with lower CD4 level and higher viral load; HGSILs were correlated
only with a lower CD4 count, and no correlations were found for LGSILs.
CONCLUSIONS: HGSILs were associated with high-risk types, mainly HPV 16 (40%).
LGSILs, instead, were associated with a broad spectrum of low-risk and high-risk
types.
PMID- 17043557
TI - Cervical cytology and other screening methods among women admitted to the medical
intensive care unit.
AB - OBJECTIVE: This study was conducted to determine whether routine gynecologic
screening is obtained for women admitted to a medical intensive care unit in a
large tertiary medical center and whether this history is used to document and
update screening for these patients. METHODS: A retrospective chart review of 65
women admitted to the medical intensive care units of Harper Hospital or Detroit
Receiving Hospital of the Detroit Medical Center over a period of one month.
RESULTS: None of the patients eligible for cervical cytology and pelvic
examination had these issues addressed in the intake history or had any of the
reviewed examinations done or planned for after discharge from intensive care.
CONCLUSIONS: Admission to intensive care is an opportunity to assess and update
routine gynecologic health screening. This important function is not routinely
addressed in the medical records of women admitted to intensive care.
PMID- 17043558
TI - Cervical cancer screening in Porto Alegre, Brazil: alternative methods for
detecting cancer precursors in a developing country.
AB - OBJECTIVE: This study was conducted to test the performance characteristics of
cervical cancer screening by visual inspection of the cervix with acetic acid and
iodine solution. METHODS: A total of 100 women were screened for cervical cancer
by Pap smear and naked eye inspection of the cervix after application of acetic
acid and iodine solution. RESULTS: Comparing visual inspection to the Pap test, a
sensitivity of 85.7%, specificity of 78.5%, and concordance of 79% (p < .0011)
was established. Comparing the Pap test with colposcopy, the corresponding
figures were 42.9%, 92.3%, and 66.6% (p < .077), respectively. Visual inspection
compared to colposcopy showed corresponding figures of 100%, 7.7%, and 55.5% (p =
.48), respectively. Colposcopy and biopsy had an agreement of 100%. CONCLUSIONS:
Visual inspection with acetic acid and iodine solution proved to be a reasonable
method of screening for cervical cancer precursors.
PMID- 17043559
TI - Human papillomavirus testing for triage in a referral population.
AB - OBJECTIVE: This study evaluated the Digene HPV Assay Hybrid Capture System(R) as
a triage method. METHODS: Results of an HPV assay were compared with a final
tissue diagnosis of cervical intraepithelial neoplasia 2 (CIN2) or greater. These
results were stratified based on Pap smear diagnosis and evaluated in 4 triage
algorithms. RESULTS: Of the 4 algorithms evaluated, the highest savings came from
not performing colposcopy for patients with repeat atypical squamous cells of
undetermined significance (ASCUS), but that resulted in missing nine patients
with CIN2 and CIN3 histology. HPV testing failed to diagnose 67% (6 out of 9) to
48% (10 out of 21) of patients with underlying CIN2 and CIN3. CONCLUSIONS:
Although HPV high-risk positive results correlate with high-grade histology, it
is associated with significant false negatives. The HPV low-risk test is not
clinically useful. These tests were poor methods to triage patients in our
population.
PMID- 17043560
TI - Treatment of cervical intraepithelial neoplasia levels 2 and 3 with adapalene, a
retinoid-related molecule.
AB - OBJECTIVES: This study examined dose scheduling, safety, and efficacy of
adapalene in the treatment of CIN2 and CIN3. METHODS: Patients were instructed on
insertion and removal of an adapalene delivery system. Treatment regimens of 4,
8, and 14 days were utilized. Biopsies were performed on day 90 to assess
efficacy. Safety was evaluated with toxicity questionnaires and patient
interviews. RESULTS: Two patients treated for 4 days had stable disease. Twenty
three patients treated for 8 days demonstrated an overall 61% (14 of 23) response
rate. Twenty-four patients treated for 14 days had an overall 38% (9 of 24)
response rate. No patient had disease progression. Compared to untreated
historical controls, significantly improved efficacy was demonstrated for
patients with CIN2. Patients with CIN3 had improved efficacy, though not
statistically significant. CONCLUSIONS: The lack of side effects and practicality
of home use make adapalene a nontoxic and safe alternative to surgical therapy in
patients with CIN2 and CIN3.
PMID- 17043561
TI - Testicular torsion: a review.
AB - Torsion of the testis, also referred to as torsion of the spermatic cord, is a
subject of debate among physicians and surgeons. Testicular torsion is an acute
vascular event causing the rotation of the vascular pedicle of the testis,
thereby impeding the blood flow to the testis and the scrotal contents. It could
be either within or outside the tunica vaginalis. Testicular torsion causes
immediate circulatory changes and long-term sequelae such as testicular function
and fertility. It is considered a surgical emergency, as a delay causes
irreversible testicular damage. The diagnosis and treatment of testicular torsion
are discussed in this review, which also illustrates an algorithm and a scoring
system for the diagnosis and management of this condition based on current
literature.
PMID- 17043562
TI - Asymptomatic lung carcinoma presenting with a large vulvar lesion.
AB - OBJECTIVE: Metastases to the vulva are infrequent, accounting for less than 10%
of vulvar tumors. Vulvar metastases from lung carcinoma have been reported in two
other cases. METHODS: A case of lung carcinoma metastatic to the vulva is
reported. RESULTS: A 71-year-old woman was referred to The University of Iowa
Hospitals and Clinics with a lung nodule on chest x-ray and a 12-cm, necrotic,
left vulvar mass. A lung biopsy showed poorly differentiated carcinoma, and a
palliative resection of the vulvar mass showed metastatic lung carcinoma. The
patient died from sepsis on postoperative day 10. CONCLUSIONS: Lung carcinoma
metastatic to the vulva is rare and portends a poor prognosis.
PMID- 17043563
TI - Home study course: winter 2001.
AB - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
practitioner who is seeking to develop or enhance his or her colposcopic skills.
The goal of the course is to present colposcopic cases that are unusual or
instructive in terms of appearance, presentation, or management, or that
demonstrate new and important knowledge in the area of colposcopy or pathology.
Participants may benefit from reading and studying the material or from testing
their knowledge by answering the questions. ACCME ACCREDITATION: The American
Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
Accreditation Council for Continuing Medical Education (ACCME) to sponsor
continuing medical education for physicians. The ASCCP designates this continuing
medical education activity for 1 credit hour in Category I of the Physician's
Recognition Award of the American Medical Association. Credit is available for
those who choose to apply. The Home Study Course is planned and produced in
accordance with the ACCME's Essential Areas and Elements.
PMID- 17043564
TI - American Society for Colposcopy and Cervical Pathology.
PMID- 17043577
TI - How should a patient with a series of mildly abnormal Pap smears be managed?
PMID- 17043578
TI - Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical
neoplasia.
AB - OBJECTIVE: To determine the ability of Multimodal Hyperspectral Imaging (MHI) to
noninvasively detect, localize and diagnose cervical neoplasia. MATERIALS AND
METHODS: The cervical epithelium was interrogated by MHI using tissue
fluorescence and reflectance measurements after the probe was placed on the
ectocervix. A Papanicolaou smear was taken, and a colposcopic examination was
performed and cervical histologic specimens were collected, when indicated. MHI
and Pap smear sensitivity and specificity data were compared with colposcopic and
histologic results. RESULTS: Nineteen patients had CIN2 or higher, 30 had CIN1,
34 had benign cellular changes or metaplasia, and 28 were normal by both Pap
smear and colposcopic examination. At equal specificity (70%) for both tests, the
sensitivity of MHI was 97%, compared to 72% for the Pap smear. CONCLUSION: MHI
detected cervical cancer precursors at a rate greater than that obtained by a
simultaneously collected Pap smear.
PMID- 17043579
TI - Reporting the potential benefits of new technologies for cervical cancer
screening.
AB - The AHCPR released its evidence-based report, "Evaluation of Cervical Cytology"
in early 1999. This report represents the most comprehensive analysis available
to date of Pap smears and new technologies designed to improve cervical cancer
screening. Both the ACOG and the AHCPR have released simplified summaries of the
results of the evidence report that may lead to misunderstandings of the
potential clinical impact of these new technologies. This report reviews the 4
major statements in these summaries and discusses how they are either incorrect
based on the full AHCPR report or may be misinterpreted because their
ramifications are not fully discussed. New screening technology has the potential
to finally bring the sensitivity of a new Pap test to an acceptable level. The
increased sensitivity afforded by these new technologies can reduce negative
outcomes at reasonable cost-effectiveness ratios and at an equivalent or superior
specificity compared to the conventional Pap smear.
PMID- 17043580
TI - Efficacy of treatment of inflammatory cytologic abnormalities detected by
papanicolaou smears: a pilot study.
AB - OBJECTIVE: To evaluate the efficacy of metronidazole versus no treatment for the
empiric treatment of inflammatory cytologic changes. MATERIALS AND METHODS:
Patients with inflammatory changes on Pap smear were serially assigned to receive
no treatment or metronidazole by one of three regimens: 2 grams orally as a
single dose, 500 milligrams orally twice daily for 7 days, or 5 grams (in gel
form) vaginally twice daily for 5 days. Smears were repeated 3 months after
treatment. RESULTS: The repeat smear was normal in 47 of 63 patients treated with
a single dose, 40 of 62 patients treated orally for 7 days, 14 of 21 patients
treated with vaginal gel, and 29 of 49 of the control group. Chi-square analysis
showed no statistical significance between groups. CONCLUSION: There is no
statistically significant difference in the resolution of cytologic inflammatory
changes among the study groups. Empiric metronidazole treatment has no benefit.
PMID- 17043581
TI - Continous flow vaginoscopy in children.
AB - The inspection of the vagina may be necessary in childhood whenever abnormal
bleeding or persistent vulvovaginitis occurs. The intact and narrow laryngeal
ring is a significant obstacle to the physician. Continuous-flow vaginoscopy
using the hysteroscope and normal saline for irrigation and distention is very
quick, easy and efficacious. Procedures, such as hemostasis, biopsy or foreign
body removal can be performed during its application.
PMID- 17043582
TI - Evaluation of the sexually abused child, including the role of colposcopy.
AB - The magnification and excellent lighting provided by the colposcope make it an
excellent diagnostic tool when enhanced direct observation is required. What can
be accomplished with this tool in a pediatric or adolescent patient depends upon
the examiner understanding how to best perform the examination related to these
age groups and knowing what they see. This article describes common techniques
used in the examination of the young gynecologic patient and common normal and
abnormal findings. This knowledge should be especially helpful to the
practitioner who is called upon to perform a sexual abuse examination in this
population.
PMID- 17043583
TI - Adenocarcinoma in situ of the cervix-controversies in diagnosis and treatment.
AB - Adenocarcinoma in situ (AIS) of the uterine cervix is a rare condition. Pap smear
screening is unsatisfactory, and the disease has no morphologic reliable
colposcopic features. Diagnosis is often made by chance during the treatment of
squamous pre-invasive disease, which commonly coexists with AIS. Although the
entire endocervical canal can be the site of disease, most lesions lie within 1
cm of the squamocolumnar junction. Skip lesions are rare, making fertility
sparing surgery a possibility under certain conditions. Recurrent disease occurs
in 14% of cases when cone margins are free of disease and rise to more than 50%
if the margins are involved. The method of conization is immaterial provided a
large enough specimen is taken and that the endocervical margins can be evaluated
by the pathologist. Follow-up of conservatively managed women is not defined;
however, we recommend that regular endocervical cytology be performed in addition
to conventional cytology and colposcopy.
PMID- 17043584
TI - Condoms or abstinence for one year then retest for hpv?
PMID- 17043585
TI - How should a patient with a series of abnormal pap smears be managed?
PMID- 17043587
TI - The american society for colposcopy and cervical pathology: hagerstown, MD.
PMID- 17043586
TI - Home study course: spring 2001.
AB - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
practitioner who is seeking to develop or enhance his or her colposcopic skills.
The goal of the course is to present colposcopic cases that are unusual or
instructive in terms of appearance, presentation, or management or that
demonstrate new and important knowledge in the area of colposcopy or pathology.
Participants may benefit from reading and studying the material or from testing
their knowledge by answering the questions. ACCME ACCREDITATION: The American
Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
Accreditation Council for Continuing Medical Education (ACCME) to sponsor
continuing medical education for physicians. The ASCCP designates this continuing
medical education activity for 1 credit hour in Category 1 of the Physician's
Recognition Award of the American Medical Association. Credit is available for
those who choose to apply. The Home Study Course is planned and produced in
accordance with the ACCME's Essential Areas and Elements.
PMID- 17043589
TI - Conservative management of adenocarcinoma in situ of the cervix.
PMID- 17043588
TI - Significance of Atypical Squamous Cells of Undetermined Significance on ThinPrep
Papanicolaou Smears.
PMID- 17043590
TI - The natural history of cervical cryosurgical healing. The minimal effect of
debridement of the cervical eschar.
PMID- 17043591
TI - Presence of human papillomavirus and epstein-barr virus in the cervix of women
infected with the human immunodeficiency virus.
PMID- 17043592
TI - Papanicolaou smear history and diagnosis of invasive cervical carcinoma among
members of a large prepaid health plan.
PMID- 17043593
TI - Accuracy of patients' recall of pap and cholesterol screening.
PMID- 17043594
TI - Healing experiences after cervical cryosurgery.
PMID- 17043595
TI - Wet smear compared with gram stain diagnosis of bacterial vaginosis in
asymptomatic pregnant women.
PMID- 17043596
TI - Mandated coverage for cancer-screening services: whose guidelines do States
follow?
PMID- 17043597
TI - Knowledge about human papillomavirus among adolescents.
PMID- 17043598
TI - Setting the target for a better cervical screening test: characteristics of a
cost-effective test for cervical neoplasia screening.
PMID- 17043599
TI - Validity of adolescent and young adult self-report of papanicolaou smear results.
PMID- 17043600
TI - Cervical shedding of herpes simplex virus and cytomegalovirus throughout the
menstrual cycle in women infected with human immunodeficiency virus type 1.
PMID- 17043601
TI - Epithelial cell layer thickness and immune cell populations in the normal human
vagina at different stages of the menstrual cycle.
PMID- 17043602
TI - Risk factors for cervical stenosis after loop electrocautery excision procedure.
PMID- 17043603
TI - Clinical evidence: issue 3, june 2000.
PMID- 17043604
TI - Letters to the editor.
PMID- 17043605
TI - Letters to the editor.
PMID- 17043606
TI - Towards a tailor made treatment of thoraco-abdominal aneurysms!
PMID- 17043607
TI - Endovascular treatment of thoracoabdominal aortic aneurysms.
AB - Open surgical repair of thoracoabdominal aortic aneurysms (TAAA) bridges the
aneurysm with a large, conventional, unstented graft and restores flow to the
visceral arteries through short grafts or direct sutured connections between the
visceral arterial orifices and the primary conduit. The combination of retrograde
visceral bypass and endovascular aneurysm exclusion substitutes an endovascular
stent-graft for a standard graft, stented overlaps for sutured anastomoses, and
transluminal insertion for direct aortic exposure. Compared to open surgery, the
combination treatment requires less dissection, and causes less hemodynamic
instability, and lower complication rates, particularly paraplegia. The multi
branched stent-graft substitutes endovascular visceral bypass through branches of
the stent-graft for surgical visceral bypass through branches of a conventional
extraluminal graft, which has the potential to further reduce surgical
dissection, hemodynamic instability, and complication rates. We favor a modular
approach in which short, axially oriented cuffs are extended into the visceral
arteries, using self-expanding covered stents. In the past year, we have used
this approach to implant multi-branched thoracoabdominal stent-graft in 16
patients. In our opinion, this approach will eventually assume a prominent role
in the management of TAAA.
PMID- 17043608
TI - Impact of the calf perforators on the venous hemodynamics in primary varicose
veins.
AB - The hemodynamic significance of the calf perforating veins continues to be the
point of controversy. The conception that incompetent perforating veins cause
hemodynamic disturbance and are responsible for the formation of leg ulceration
has still many adherents prefering perforator surgery, whereas others reject any
causal relation between large, incompetent perforators and severe forms of
chronic venous insufficiency. In this study well documented facts concerning the
impact of the calf perforators on the venous hemodynamics are reviewed. There is
a bidirectional flow within calf perforators in healthy subjects enabling a quick
equilibration of pressure changes produced during calf muscle contractions and
relaxations, so that recordings of the mean pressure display identical values in
superficial and deep veins of the lower leg, a feature typical of conjoined
vessels. In cases with saphenous reflux, the bidirectional flow within calf
perforators has a distinct inward vector directed to the deep veins; this inward
component is the more pronounced, the larger the saphenous reflux is. Incompetent
calf perforators do not cause ambulatory venous hypertension, exactly the
opposite happens: the high hydrostatic pressure found in the quiet standing
position drops significantly during ambulation, as soon as the saphenous reflux
is interrupted. In primary varicose veins calf perforators can not become the
source of reflux because they are situated at the lower pole of the ambulatory
pressure gradient, which occurs between thigh and lower leg veins during
ambulation. The size of the calf perforators is determined by the amount of
saphenous reflux. When the saphenous reflux is abolished (e.g. by high ligation),
the enlarged calf perforators diminish.
PMID- 17043609
TI - Abdominal aortic aneurysm surgery: retroperitoneal or transperitoneal approach?
AB - AIM: Mortality and morbidity of abdominal aortic aneurysm surgery have decreased
significantly in time and transperitoneal approach (TPA) still preserves its
popularity although retroperitoneal approach (RPA) is known to cause lower
incidence and shortened duration of ileus, shorter intensive care unit (ICU) and
hospital stay, earlier oral intake and less patient discomfort or pain. METHODS:
One hundred and fifty patients that underwent abdominal aortic aneurysm repair at
our Cardiovascular Surgery Center between January, 1990 and March, 2000 were
reviewed and analyzed based on the elective/emergent nature of the surgery and
the type of the incision as either TPA or RPA. RESULTS: Significantly shorter
mechanical ventilation (15.2+/-3.8 vs 10.1+/-2.3 hours) and nasogastric
decompression periods (40.6+/-10.7 vs 9.1+/-2.2 hours), less need for intravenous
fluid supplementation and shorter ICU stay (29.5+/-14.8 vs 18.6+/-1.9 hours) were
observed with the retroperitoneal approach (P<0.001). Need for allogeneic blood
transfusion was, similar (1.3+/-1.4 vs0.9+/-0.4, P>0.05). Analysis of mortality
and morbidity revealed bleeding as the major cause of mortality for ruptured
aneurysm. A similar comparison between TPA and RPA groups, however, revealed no
significant difference (P>0.05). CONCLUSIONS: | Retroperitoneal approach is a
reliable technique causing less fluid-electrolyte imbalance with rapid
restoration of gastrointestinal physiology. It causes less discomfort to patients
with reduced need for analgesia. A shorter weaning period from mechanical
ventilation is among the benefits for patients with co-morbid states.
PMID- 17043610
TI - Surgical treatment of abdominal aortic aneurysm with concomitant renal cell
carcinoma: a single-centre experience with review of the literature.
AB - AIM: The association between abdominal aortic aneurysm (AAA) and renal cancer is
becoming more frequent, raising several questions about therapeutic and surgical
strategies of management for both diseases. METHODS: Between October 1988 and May
2004, 913 AAA patients underwent surgical or endovascular repair at the I
Division of General Surgery of the University of Verona (Italy). In 61 cases
(6.7%) an association with a solid neoplasm was found; in 12 cases (1.3%) the
neoplasm was a renal cell carcinoma. RESULTS: Ten patients underwent a
simultaneous approach to AAA and renal cancer, with aneurismectomy performed
first. In 2 cases a two-stage procedure was preferred; 1 patient underwent
aneurismectomy first for AAA rupture while a second patient was even affected by
gastric cancer and was submitted to nephrectomy and total gastrectomy as primary
procedures. There was no mortality and only one postoperative complication was
registered. CONCLUSIONS: A simultaneous surgical approach can be done safely,
performing aneurismectomy as first step without significant risk of graft
infection. Simultaneous treatment has the advantage of avoiding a second major
abdominal procedure and eliminate the risk of postoperative aortic aneurysm
rupture. Performing a two-stage approach, the procedure for the disease regarded
as life-threatening is performed first. Priority should be given to renal cell
neoplasm in selected cases.
PMID- 17043611
TI - Early and medium-term results of stent-graft treatment of DeBakey type III aortic
dissection.
AB - AIM: The safety and effectiveness of transcatheter stent-graft treatment in the
early and medium-term postoperative period was assessed in patients with DeBakey
type III aortic dissection. METHODS: Transcatheter stent-graft implantation was
performed in 37 patients who had aortic dissection with entry sites in the
descending thoracic aorta. Entry sites were closed with a stent-graft consisting
of a Gianturco Z stent covered with an UBE woven Dacron graft. RESULTS: There
were no in-hospital deaths or serious complications after operation. In 5
patients, a new intimal tear developed at the distal end of the stent-graft 8 to
13 months after operation. It was closed by additional stent-graft placement in 2
patients. The rate of thrombosis of the false lumen of the descending thoracic
aorta 5 to 10 days, 3 to 6 months, and 12 months after operation was 70%, 80%,
and 81%, respectively. As compared with before operation, the short axis of the
true lumen increased (1.4+/-0.8 cm before operation, 2.1+/-0.5 cm at 5-10 days,
and 2.7+/-0.6 cm at 3-6 months) and that of the false lumen decreased (2.9+/-0.9
cm, 2.3+/-0.9 cm, 1.5+/-1.2 cm), indicating enlargement of the true lumen and
shrinkage of the false lumen. The false lumen was completely obliterated within 3
6 months after operation in 6 patients. CONCLUSIONS: Our early postoperative
results show that transcatheter stent-graft implantation is a safe and effective
procedure for the management of DeBakey Type III aortic dissection. Devices with
a minimal risk of causing intimal tears should be developed.
PMID- 17043612
TI - Risk factor analysis for ascending aorta and aortic arch repair using selective
cerebral perfusion with open technique: role of open-stent graft placement.
AB - AIM: The present study was designed to identify risk factors that may induce
adverse outcome defined as permanent neurological dysfunction and mortality after
aortic arch surgery using selective cerebral perfusion by logistic regression
analysis and to reveal the role of open stent-graft placement. METHODS: One
hundred and nineteen consecutive patients underwent ascending aorta and/or aortic
arch operation with open technique between 1995 and 2005 were examined. Ascending
aorta and/or hemiarch was replaced in 28 patients, total arch in 75 patients, and
proximal or distal aortic arch replacement in 16 patients. Open stent-graft
placement was used in 25 patients. RESULTS: The in-hospital mortality rate was
9.2%. Permanent neurological dysfunction occurred in 10 patients (8.4%).
Thoracotomy (P=0.0331) and cardiopulmonary bypass time (P=0.0238) were
significant risk factors for permanent neurological dysfunction. Preoperative
shock (P=0.0266) was significant independent risk factor for mortality. Emergent
operation (P=0.0454), thoracotomy (P=0.0232), and cardiopulmonary bypass time
(P=0.0379) were significant independent risk factors for adverse outcome. The
duration of selective cerebral perfusion was not associated with adverse outcome.
Open stent-graft placement has no need of thoracotomy for aneurysm extending
descending thoracic aorta and time variables concerning the operation were
significantly shorter in the patients with open stent-graft placement than in
patients with standard operation for total arch replacement. RESULTS: Thoracotomy
was significant risk factor for adverse outcome after aortic arch repair using
selective cerebral perfusion. Total arch replacement with open stent-graft
placement can avoid the need of thoracotomy and reduce time variables concerning
the operation to improve the surgical
PMID- 17043613
TI - Early graft thrombosis after endovascular aortic aneurysm repair with aortouni
iliac endografts.
AB - Endovascular repair of aortic aneurysm has become a viable treatment option in
selected patients. However, despite the minimally invasive nature ot this
treatment a significant incidence of vascular complications has been reported.
Here, we report two cases of acute limbs ischemia due to endograft thrombosis in
patients treated with aortouni-iliac devices and we review the etiologic factors
related with these events and the treatment options. We suggest that the presence
of atherosclerotic plaques within the outflow arteries and coexistent
infrainguinal arterial occlusive disease (poor runoff) is an underestimated
factor in the risk of graft thrombosis, especially in patients treated with
aortouni-iliac devices and we advocate the use in the early follow-up
surveillance after endovascular repair of aortic aneurysm of noninvasive test
such duplex scanning, segmental pressures and ankle-brachial indices to asses the
presence or progress of coexistent occlusive disease. We also suggest that some
adverse outcomes ascribed to device failure might be more properly charged to
inappropriate patient selection.
PMID- 17043614
TI - Effect of cold blood cardioplegia enriched with potassium-magnesium aspartate
during coronary artery bypass grafting.
AB - AIM: The aim of this investigation is to evaluate the effect of enriched with
potassium-magnesium aspartate cold-blood cardioplegia on early reperfusion injury
and postoperative arrhythmias in patients with ischemic heart disease undergoing
coronary artery bypass grafting (CABG), using measurements of cardiac troponin I
(CTnI), hemodynamic indexes and clinical parameters. METHODS: Forty patients with
three-vessel coronary artery disease (CAD) and stable angina, receiving first
time elective CABG, were randomly divided into 2 groups: patients in control
group (C group n=20) received routine institutional cold blood cardioplegia (4
degrees C) concentration of Mg2+4 mmol/L, Ca2+1.2 mmol/L and K+ 24mmol/L during
myocardial arrest. Patients in P group (n=20) received modified cold blood
cardioplegia enriched with potassium-magnesium aspartate and maintained
concentration of Mg2+10 mmol/L, Ca2+1.2 mmol/L and K+20mmol/L in the final blood
cardioplegia solution. Clinical outcomes were observed during operation and
postoperatively. Serial venous blood samples for CTnI were obtained before
induction, after cardiopulmonary bypass (CPB), and postoperative 6, 24, and 72
hours. Hemodynamic indexes were obtained before and after bypass by the radial
catheter and Swan-Ganz catheter. RESULTS: In both groups, there were no
differences regarding preoperative parameters. There were no cardiac related
deaths in either group. The time required to achieve cardioplegic arrest after
cardioplegia administration was significantly shorter in P group (47.5+/-16.3 s)
than in C group (62.5+/-17.6 s) (P<0.01). The number of patients showing a return
to spontaneous rhythm after clamp off was significantly greater in P group (n=20,
100%) than in C group (n=14, 70%) (P<0.01). Eight patients in C group had atrial
fibrillation (AF) compared with two patients in P group (P<0.05) in the early of
postoperative period. The level of CTnI increased 6 hours and 12 hours
postoperatively, and there was a significant difference between groups (P<0.05).
P group also shortened the time of postoperative mechanical ventilation (P<0.05)
after surgery. CONCLUSIONS: Cold blood cardioplegia enriched with potassium
magnesium aspartate is beneficial on reducing reperfusion injury.
PMID- 17043615
TI - Benefits of terminal noncardioplegic warm blood retrograde perfusion after
terminal warm blood cardioplegia perfusion prior to aortic unclamping in open
heart surgery.
AB - AIM: The benefits of terminal noncardioplegic warm blood retrograde perfusion
(TNWB) and terminal warm blood cardioplegia perfusion (TWBC) after intermittent
cold blood cardioplegia perfusion during aortic clamping were studied. METHODS:
The clinical results of consecutive 128 patients who underwent on pump coronary
artery bypass grafting (CABG) or valvular surgery were studied retrospectively.
The aortic cross-clamp was removed (1) after five-minute TWBC and sequential
three-minute TNWB in 59 patients (TNWB group), (2) immediately after five-minute
TWBC in 29 patients (TWBC group), or (3) with neither TWBC or TNWB in 36 patients
(control group). RESULTS: The incidence of spontaneous heart beat recovery was
best in TNWB group, second in TNBC, and worst in control group (TNWB: 86, TWBC:
42, CONTROL: 14%). The duration from aortic unclamping to heart beat recovery was
shorter in TNWB group than TWBC group (TNWB: 2.1, TWB: 4.3 min). Cardiopulmonary
bypass duration after aortic unclamping was shortest in TNWB group, second in
TWBC group, and longest in control group (TNWB: 21.3, TWB: 27.5, CONTROL: 46.9
min). The postoperative CPK-MB was lowest in TNWB group (TNWB: 65.3, TWB: 87.7,
CONTROL: 91.9U/L). Duration of intubation in TNWB group or TWBC group was shorter
than control. CONCLUSIONS: Combination of the terminal noncardioplegic warm blood
perfusion and terminal warm blood cardioplegic perfusion contributes to increase
the incidence of spontaneous heart beat recovery, shortens cardiopulmonary bypass
duration following aortic unclamping, and lowers postoperative CPK-MB.
PMID- 17043616
TI - Incremental risk of obstructive sleep apnea on cardiac surgical outcomes.
AB - AIM: Obstructive sleep apnea (OSA) is not generally acknowledged as a
perioperative risk factor. High incidence of Sleep disordered breathing has been
noticed in patients with cardiovascular disease. The Sleep Heart Health Research
Study Group found Apnea-Hypopnea indices (AHI) as modest as 1-10 to be associated
with cardiovascular disease manifestations. Given the lack of data we chose to
study the incremental risk of OSA in patients undergoing cardiac surgery.
METHODS: We looked at 25 587 patients who underwent cardiac surgery at the
Cleveland Clinic. Of these, 37 patients were also identified on the Cleveland
Clinic Sleep center database as having OSA. Each of these 37 cases were
propensity matched for multiple covariates with 5 controls within a distance of
0.001 units. An assumption was made that if the surgery was performed within two
years of the diagnosis of OSA, the patient had OSA at the time of the surgery.
RESULTS: Higher incidence of encephalopathy (p=0.008), postoperative infection
(0.028) and increased ICU length of stay (p=0.031) were noted in the group with
OSA after cardiac surgery. The difference in the rates of infection was mostly
accounted for by the presence of mediastinitis (8.1% vs 1.6%). Differences in the
rates of reintubation, tube time, and overall postoperative morbidity were not
statistically significant. CONCLUSIONS: | Increased risk for postoperative
complications is suggested in patients with OSA undergoing cardiac surgery. This
risk is underestimated on account of lack of awareness about the incidence of OSA
in the general population and the cardiovascular population in particular,
difficulties in clinical suspicion and diagnosis and limited use of
polysomnography.
PMID- 17043617
TI - Nine years experience of aortic arch repair with the aid of antegrade selective
cerebral perfusion.
AB - AIM: Antegrade selective cerebral perfusion (ASCP) is gaining widespread
popularity in aortic arch surgery because it has been demonstrated to be an
optimal technique of cerebral protection. This study demonstrates the clinical
results of aortic arch repair with ASCP. METHODS: Between November 1996 and
September 2004, 250 patients underwent thoracic aorta replacement using ASCP
under moderate hypothermia. Mean patients age was 63+/-11.5 years. Presenting
pathologies were chronic aneurysm in 136 patient (54.4%), type A acute aortic
dissection in 80 patients (32%), post-dissection aneurysm in 30 patients (12%).
Ascending aorta and hemiarch replacement was performed in 63 patients (25.2%),
ascending aorta and total arch replacement in 131 patients (52.4%), total arch
replacement in 33 patients (13.2%), total arch and descending aorta replacement
in 10 patients (4%) and complete replacement of the thoracic aorta in 13 patients
(5.2%). RESULTS: Hospital mortality was 11.6%. Multivariate analysis showed
preoperative renal failure (P=0.050), cerebral perfusion time (P<0.001),
pulmonary complications (P=0.009) and postoperative dialysis (P=0.030) as risk
factors for hospital mortality. Permanent neurologic deficits occurred in 4
patients (1.6%) and coronary artery disease (P=0.029) was found to be the only
independent risk factor. Transient neurologic deficits were noted in 18 patients
(7.2%). Multivariate analysis revealed age (P=0.043), coronary artery disease
(P=0.036), urgent/emergency status of the operation (P=0.016) and concomitant
aortic valve replacement (P=0.001) to be independent predictors of transient
neurologic dysfunction. The actuarial survival rate at 7 years was 61.7%.
CONCLUSIONS: | Our results confirmed that ASCP is a safe method of brain
protection allowing complex aortic repairs to be performed with good results in
terms of hospital mortality and neurologic outcome. Cerebral perfusion time did
not influence postoperative outcome. The use of moderate hypothermia avoided all
undesirable effects of deep hypothermia.
PMID- 17043618
TI - Extracardiac Fontan operation without cardiopulmonary bypass.
AB - AIM: The avoidance of cardiopulmonary bypass and aortic cross-clamping in
patients possessing single ventricular physiology has potential advantages
including preservation of ventricular and pulmonary functions; early extubation,
decreased incidence of pleural effusions and decreased requirement of inotropic
agents and blood products. In this study, we assessed the postoperative outcome
of patients who have undergone extracardiac Fontan operation performed without
cardiopulmonary bypass. METHODS: Between March 1999 and August 2002, 10
consecutive patients (6 males and 4 females) underwent extracardiac Fontan
operation without cardiopulmonary bypass. The age of patients ranged between 1.5
to 12 (5.2+/-3.1) years. All the patients requiring any intracardiac intervention
were excluded from the study. Previous operations of the patients were modified
Blalock-Taussig shunt procedure in 3 patients, bidirectional cavopulmonary shunt
operation in 2 patients and pulmonary arterial banding in 1 patient. All
operations were performed without cardiopulmonary bypass. Bidirectional
cavopulmonary anastomosis was performed by using a transient external shunt
constructed between the superior vena cava and right atrium. An appropriate sized
tube graft was anastomosed to the inferior surface of right pulmonary artery.
Finally, inferior vena cava to tube grafts anastomosis was performed with the aid
of another external shunt constructed between inferior vena cava and right
atrium. During the procedure central venous pressure, blood pressure and arterial
oxygen saturation levels were continuously monitored and recorded. RESULTS: The
mean intraoperative Fontan pressure was 16.1+/-2.75 mmHg. Intraoperative
fenestration was required in 4 patients with a Fontan pressure above 18 mmHg.
There were no intra and postoperative deaths. Three patients required mild doses
of inotropic support during the postoperative period. All patients were weaned
off mechanical ventilation within 24 h. The mean arterial oxygen saturation
raised from 74.5+/-4.2% to 93.5+/-2%. Arterial oxygen saturation was 95+/-0.6% in
6 patients without fenestration and 91.2+/-0.5% in 4 patients with fenestration
(P=0.001). All patients were in sinus rhythm postoperatively. Only 2 patients
required blood transfusion. Two patients suffered from prolonged pleural effusion
(more than 7 days). The mean intensive care unit and hospital stay periods were
3.3+/-1.5 and 15.4+/-5.3 days, respectively. CONCLUSIONS: The extracardiac Fontan
operation performed without cardiopulmonary bypass provides good results in short
and midterm follow-up periods with improved postoperative hemodynamics.
PMID- 17043619
TI - Surgical treatment of atrial fibrillation with bipolar radiofrequency ablation:
mid-term results in one hundred consecutive patients.
AB - AIM: The Cox-Maze procedure was introduced nearly two decades ago for the
surgical treatment of atrial fibrillation (AF). Recently, our group has replaced
most of the incisions of the Cox-Maze procedure with bipolar radiofrequency (RF)
ablations (Cox-Maze IV procedure). The purpose of this study was to examine our
midterm results with the Cox-Maze procedure using bipolar RF ablation. METHODS:
From January 2002 to October 2005, 100 consecutive patients underwent a modified
Cox-Maze procedure with bipolar RF ablation for AF; 32 were lone operations, and
68 were concomitant procedures. Follow-up was performed at 1, 3, 6, and 12
months, and then annually thereafter. Heart rhythm was confirmed by
electrocardiography. RESULTS: The mean age of patients was 62+/-13 years; 57%
were male. Duration of AF was 6.3+/-7.6 years (0.1 to 40 years), 59% had
paroxysmal AF, and 34% had permanent AF. Follow-up was complete for all patients
with a mean follow-up of 13+/-10 months. At 12-month follow-up, 91% (49/54) of
patients were free of AF. Cross-clamp time in the lone Cox-Maze IV procedure
patients was 42+/-15 minutes, while it was 101+/-29 minutes for the Cox-Maze IV
with a concomitant procedure (compared to 93+/-34 minutes and 122+/-37 minutes
for the traditional procedure, P<0.05). There were four operative deaths.
CONCLUSIONS: The Cox-Maze IV procedure had good mid-term efficacy. The use of
bipolar RF energy significantly decreased operative time and simplified the
procedure compared to the traditional Cox-Maze procedure, potentially increasing
utilization of the procedure among cardiac surgeons.
PMID- 17043620
TI - A multi-step approach in anti-calcification of glutaraldehyde-preserved bovine
pericardium.
AB - AIM: Bioprosthetic cardiovascular substitutes, manufactured from glutaraldehyde
preserved bovine or porcine tissues, are prone to calcification after
implantation. The aim of the study was to evaluate the ultrastructure, material
stability and calcification behaviour of glutaraldehyde-preserved bovine
pericardium, treated with a multi-step anti-calcification process which addresses
each of the major causes of calcification and tissue degeneration. METHODS:
Bovine pericardium samples were divided into 2 groups. Group I (control)
consisted of tissue fixed with 0.625% glutaraldehyde and Group II (study group)
consisted of tissue fixed with 0.625% glutaraldehyde and exposed to a multi-step
anti-calcification process. Ultrastructure was examined by scanning electron
microscopy and material stability was assessed by mechanical testing, shrinkage
temperature and enzymatic degradation. Calcification was assessed by histology
(Von Kossa stain) and by atomic absorption spectrophotometry in the subcutaneous
rat model. RESULTS: Bovine pericardium in the study group revealed less visible
changes in the ultrastructure of the collagen matrix, improved material stability
(P<0.05) and significantly (P<0.001) reduced calcification compared to control
tissues (4.5+/-1.2 versus 136.03+/-11.39 ug/mg tissue). CONCLUSIONS: In
conclusion, results demonstrate that the multi-step anticalcification process
improved the material stability and reduced the calcification potential of bovine
pericardial tissue. These improvements in the quality of the bovine pericardium
should enhance the long-term durability of the tissue as a bioprosthetic
substitute for cardiovascular application.
PMID- 17043622
TI - Communicating across the boundaries.
PMID- 17043621
TI - Comparison of a beta-blocker and an If current inhibitor in rabbits with
myocardial infarction.
AB - AIM: We compared protective effects of a ss-adrenoceptor blocker (metoprolol;
Met) and a If current (Ivabradine; Iva) in a rabbit model of myocardial
infarction. METHODS: Experiments were performed on 44 adult New-Zealand-White
(NZW) rabbits. The effects of either metoprolol or ivabradine were assessed 15
min after experimental occlusion of a coronary artery (CAO), 28 days after CAO
(drug gavage), and in vitro hearts (Langendorff apparatus). The results were
compared with sham and placebo hearts. RESULTS: Metoprolol (0.25 mg/kg) slightly
reduced heart rate and left ventricular systolic function. Ivabradine (0.25
mg/kg) reduced heart rate significantly (P<0.05) (18% vs control). Both drugs
provided advantages over placebo: mortality was significantly (P<0.01)smaller
(6/13 Pla animals died, 2/10 Met animals, and 3/11 Iva animals), left ventricular
function was better preserved after 28 days (external power; Pla; Met; Iva=56%;
76%; 74%), and dilatation (BNP) was reduced (P<0.05). In the Pla group, the ST
segment was significantly (P<0.05) elevated by 0.35 mV after CAO and exhibited in
50% of the animals Q waves after 28 days, while after ivabradine or metoprolol,
ST displacement and Q waves had disappeared. The uneconomic myosin isoenzyme V3
predominated in Met hearts and Iva hearts (V3/V1: 63/37% and 62/38%), while it
was further increased in Pla hearts (78/21%). External efficiency was lowest in
Pla hearts (1.00+/-0.50 a.u.; P<0.05) and was significantly higher both in Met
hearts (4.0+/-1.8 a.u.) and in Iva hearts (3.3+/-1.6 a.u.). CONCLUSIONS: Met and
Iva seem suited for the treatment of chronic myocardial infarction.
PMID- 17043623
TI - Advances in cancer therapy with radiolabeled monoclonal antibodies.
AB - Two radiolabeled antibody products for the treatment of non-Hodgkin's lymphoma
have been approved, thus indicating that cancer radioimmunotherapy (RAIT) has
finally come of age as a new therapeutic modality, exemplifying the collaboration
of multiple disciplines, including immunology, radiochemistry, radiation
medicine, medical oncology, and nuclear medicine. Clinical trials are showing
usefulness in other hematological neoplasms, but the treatment of solid tumors
remains the major challenge, since the doses shown to be effective in
hematological tumors are insufficient in the more common epithelial cancers.
Nevertheless, use of RAIT in locoregional applications and in the treatment of
minimal residual disease have shown promising RESULTS: There is also optimism
that pretargeting procedures, including new molecular constructs and targets,
will improve the delivery of radioactivity to tumors with less hematologic
toxicity, and thus may become the next generation of RAIT.
PMID- 17043624
TI - Practical aspects of peptide receptor radionuclide therapy with [177Lu][DOTA0,
Tyr3]octreotate.
AB - Lutetium-177 is increasingly used in patients for receptor-targeted radionuclide
therapy with peptides such as [DOTA0,Tyr3]octreotate. In our therapy facility, we
are performing yearly 400 treatments with each 7.4 GBq
[177Lu][DOTA0,Tyr3]octreotate. Finger dosimetry data during radiolabeling reveal
higher doses on the right hands of right-handed workers with the highest
equivalent dose for the middle finger (53+/-12 microSv/GBq). Extrapolating
dosimetry data, assuming 400 doses of 7.4 GBq per year performed by 4 workers,
result in a mean equivalent dose of 23+/-11 mSv and 14+/-6 mSv for finger top and
ring dose, respectively. Preparation of 400 doses will result in an effective
dose of 0.5-1.5 mSv per year for these 4 workers. The extra radiation dose for
workers during the radiolabeling of these doses thus remains below 10% of the
legal annual limits, which is in accordance with the ALARA optimization
principle. Based on measurements of the maximal radiation level at 1 m distance
(7.5+/-3.6 microSv/h), patients treated with 7.4 GBq
[177Lu][DOTA0,Tyr3]octreotate can already leave the therapy facility the next
day. As radioactive waste streams are based on the half-lives of the used
radionuclides, 177Lu-waste (t1/2=6.7 d) was initially collected along with the
131I-waste (t1/2=8 d). According to both manufacturers' specifications, 177Lu
contains less than 0.4 kBq 177mLu/MBq 177Lu (at the end of neutron irradiation),
when produced by the [176Lu n, gamma 177Lu] reaction via thermal neutron
bombardment of enriched lutetium oxide. Unfortunately, because of the huge
amounts of 177Lu used, contaminating 177mLu turned out to prevent the quick
discharge of this waste, for some containers even after some years of storage.
Therefore, a technique for calibrating 177mLu was developed, simultaneously
confirming the manufacturer's specifications on the presence of 177mLu in 177Lu.
Subsequently a reliable technique was developed to measure 177mLu in waste
containers using a beta/gamma-contamination monitor. It is advised to collect
177mLu/177Lu-waste and certainly high-activity lutetium waste separated from 131I
according the regulations in the country of use. Apart from the mentioned waste,
excreta from patients are collected in decay tanks, where they are stored for 1-2
months before they are discarded into the general sewer within the overall
tolerated discharge limit (150 radiotoxicity equivalents/year for our
department).
PMID- 17043625
TI - Peptide receptors in neuroendocrine tumors of the lung as potential tools for
radionuclide diagnosis and therapy.
AB - Neuroendocrine tumors of the lung are carcinomas characterized by different
impact on the patients' prognosis, ranging from relatively indolent, low- to
intermediate-grade neoplasms with longer life expectation (i.e., typical and
atypical carcinoids) to very aggressive and poorly differentiated neoplasms with
dismal prognosis (i.e., large cell neuroendocrine carcinoma and small cell lung
cancer). The standard treatment of typical or atypical carcinoids is the complete
surgical resection, whereas the role of radio-chemotherapy in a multimodality
treatment or for palliation remains controversial. Conversely, high-grade
neuroendocrine carcinomas are in primis treated by aggressive combination
chemotherapy, deserving surgical resection for uncommon low-stage tumors. Since
evidence has been accumulated that neuroendocrine tumors of the lung are supplied
with a wide array of peptide receptors detectable on cell membranes by
immunohistochemical methods, innovative strategies for diagnosis and
radiometabolic therapy have been devised to target these molecules for the
correct clinical management of the patients. In this paper, the structural and
functional aspects and the clinical applications of the detection of several
peptide receptors in pulmonary neuroendocrine tumors will be reviewed, including
somatostatin receptors, vasoactive intestinal peptide/pituitary adenylate cyclase
activating peptide family receptors, cholecystokinin /gastrin receptors,
bombesin/gastrin releasing peptide receptors, neurotensin receptors, substance P
receptors, neuroepeptide Y receptors, calcitonin/calcitonin gene-related peptide
receptors, atrial natriuretic peptide receptors, glucagon-like-peptide-1
receptors, oxytocin receptors and endothelin receptors. Only a detailed knowledge
of the peptide receptor distribution in these tumor types, especially in uncommon
neoplasms such as atypical carcinoids and large cell neuroendocrine carcinomas,
is pivotal for planning the most adequate interventions for the patients'
diagnosis and therapy.
PMID- 17043626
TI - Systemic and locoregional dosimetry in receptor radionuclide therapy with
peptides.
AB - This paper reviews the methods for calculating dosimetry both after systemic or
locoregional injection of radiolabelled peptides. Radiopharmaceutical
characteristics, data processing and dosimetric outcomes are reported. The
biological effective dose, based on the linear quadratic model, is finally
described.
PMID- 17043627
TI - Vascular tumor targeting.
AB - The growth of solid tumors is dependent on their capacity to acquire blood
supply. Therefore, much effort has been directed towards the development of anti
angiogenic agents which inhibit the process of neovascularization. More recently,
it has become apparent that the targeted destruction of the established tumor
vasculature represents a complementary avenue for growing therapeutic
opportunities. This review provides evidence that vascular tumor targeting is an
effective anti-tumor strategy in animal models. It further describes strategies
for the identification of putative tumor vascular targets and discusses future
prospects for vascular targeting applications in the clinical setting.
PMID- 17043628
TI - Lutetium-177-labeled gastrin releasing peptide receptor binding analogs: a novel
approach to radionuclide therapy.
AB - Optimization of therapy for individual patients remains a goal of clinical
practice. Radionuclide imaging can identify those patients who may benefit from
subsequent targeted therapy by providing regional information on the distribution
of the target. An ideal situation may be when the imaging and the therapeutic
compounds are the same agent. Two antibodies ([ [90Y]ibritumomab,
[131I]tositumomab) are now approved for the systemic radiotherapy of non
Hodgkin's lymphoma. The main hurdle is to deliver higher absorbed doses to the
more refractory solid tumors paying particular regard to the bone marrow
toxicity. The low dose is thought to be a result of the large size of antibodies
slowing delivery to the target. Peptides having high affinity to receptors
expressed on cancer cells are a promising alternative. They are usually rapidly
excreted from the body through renal and/or hepatobiliary excretion thus creating
a prolonged accumulation of the radioactivity in the kidneys, which represents a
recognized issue for systemic radiotherapy. The first radiopeptide developed was
a somatostatin analogue, which led to a major breakthrough in the field. Beside
the kidney issue, somatostatin use remains limited to few cancers that express
receptors in sufficiently large quantities, mainly neuroendocrine tumors. The
gastrin releasing peptide (GRP) receptor is an attractive target for development
of new radiopeptides with diagnostic and therapeutic potential. This is based
upon the functional expression of GRP receptors in several of the more prevalent
cancers including prostate, breast, and small cell lung cancer. This review
covers the efforts currently underway to develop new and clinically promising GRP
receptor specific molecules labeled with imageable and therapeutic radionuclides.
PMID- 17043629
TI - Current status and perspectives in alpha radioimmunotherapy.
AB - Systemic administration of radiolabeled antibody directed against tumor antigens
in radioimmunotherapy (RIT) enables to specifically target the cancer cells and
to destroy them. So far, this strategy has proven its efficiency in the treatment
of some hematological cancers with antibodies labeled with beta emitting
radionuclides. In the last 2 decades, availability of short half life alpha
emitters prompted to consider their use in RIT. Contrary to beta particles, alpha
particles have a short path length and display a high lineic energy transfer.
Those physical characteristics open new fields of clinical applications
complementary to beta-RIT. To date, alpha-RIT is still at a preclinical stage of
development: the radiolabeling methods need to be optimized to ensure in vivo
stability of the radiopharmaceuticals. Some radionuclides have complex decay
schemes with daughters emitting further alpha particles whose toxicity needs to
be investigated. The modalities of administration of radiolabeled antibodies in
animal models require also to be improved for delivering higher doses to tumor
targets. A comprehensive analysis of the specific events occurring at cell or
tissue level in response to alpha irradiation would be of great interest in order
to define the best therapeutic association for residual disease or consolidation
treatments. This approach has been proven to be efficient in increasing antitumor
response either by using high doses with organ protection (kidney, bone marrow)
or by a synergistic effect between alpha-RIT and associated treatments, such as
chemotherapy.
PMID- 17043630
TI - Platelet function after single [153Sm]EDTMP therapy in prostate cancer.
AB - AIM: Aim of the study was to assess whether [153Sm] EDTMP therapy at a low-dose
is associated with platelet activation. METHODS: In 29 patients suffering from
metastatic prostate cancer platelet count and various platelet function
parameters have been monitored for 2 months after a single (the first)
application of 1.1 GBq mCi [153Sm]EDTMP. RESULTS: After 3 days insignificant
signs of platelet activation (increase in malondialdehyde, adenosine diphosphate
induced platelet aggregation, decreased platelet sensitivity) occur, normalizing
rapidly. At the nadir of platelet count (3-4 weeks) platelet aggregation response
in non-count adjusted samples is somewhat lower, while activity per cell (count
adjusted samples) is unchanged. Platelet proteins do not change at all.
Insignificant activation of platelet function at day 3 is interpreted as an
indicator of mild oxidation injury, late aggregation response changes in non
adjusted samples seem only to reflect temporarily decreased number of circulating
platelets. Samarium-153-EDTMP therapy at doses (1.1 GBq) used in the Vienna
protocol is not associated with a significantly altered functional behavior of
platelets. CONCLUSIONS: We conclude that a single dose of 1.1 GBq 153Sm-EDTMP
does not significantly affect in vivo and ex vivo platelet function.
PMID- 17043631
TI - Modification of low-density lipoprotein during radiolabeling with 99mTc using
three labeling methods.
AB - AIM: The mechanisms of native low-density lipoprotein (LDL) uptake by monocytes
and macrophages via the specific cholesterol down-regulated LDL-receptor differs
form the mechanism responsible for the unregulated scavenging of the modified,
for example, oxidized LDL, by the atherosclerotic plaques and foam cells. For
this reason, we investigated if the 99mTc-labeled LDL stands for the native or
modified molecule. The influence of the LDL sampling methods, isolation,
preparation and radiolabeling of lipoproteins on structure modification and the
subsequent imaging behavior has as yet not been addressed in detail. METHODS:
Herein we present data on the effects of 99mTc labeling on some oxidation
relevant parameters of LDL, such as the lag-time, thiobarbituric acid reactive
substances (TBARS), relative electrophoretic mobility (REM), baseline dienes
(BD), lipid peroxides (POX), free amino-groups (NH2-groups) and free sulphydryl
groups (SH-groups). Three methods of 99mTc labeling were compared: dithionite
method (1), borohydride method (2) and ascorbic acid method (3). Data for
oxidation parameters are expressed as a percent of freshly isolated native LDL (%
native LDL) or as a percent of LDL treated with the labeling buffers and
reagents, but in absence of the radioisotope (% control LDL). RESULTS: The levels
of BD were most influenced by methods 2 and 3, and remained almost unchanged when
the method 1 was used. The lag-time of 99mTc-LDL produced by method 2 doubled but
it was decreased by 23% when the method 3 was employed. No change in the lag-time
compared to the native LDL was observed with the method 1. The TBARS levels were
3-5 fold higher than in native LDL when methods 1 and 2 were used, but 33% lower
in products made by the method 3. The number of thiol groups increased 3 fold in
method 1, was only slightly elevated in method 3, but reduced in method 2
compared to native LDL. NH2-groups were increased with all three labeling
procedures, but this increase was not considered significant. REM was altered
only in products obtained by methods 1 (1.5x increase) and by method 2 (1.25x
increase). No fragmentation of Apo B using sodium dodecyl sulfate polyacrylamide
gel (SDS-PAGE) electrophoresis was observed by 99mTc-LDL produced in any of the
METHODS: The increase of lipid peroxide generation was observed only when the
method 2 was used. CONCLUSIONS: Of the three tested methods, we found all of them
to render LDL oxidatively modified to some extent. Therefore, it appears that the
native-LDL imaging with 99mTc-labeled LDL is impossible. Only the ascorbic acid
method 3 appears to offer some protection and exerts antioxidant effects.
PMID- 17043632
TI - Chromogranin A immunoradiometric assay in diagnosis of pheochromocytoma:
comparison with plasma metanephrines and 123I-MIBG scan.
AB - AIM: The aim of this study is to investigate the diagnostic performance of serum
chromogranin A (CgA) and plasma metanephrines (MN) assays in the diagnosis of
pheochromocytoma. METHODS: We enrolled 44 patients affected by histologically
proved adrenal pheochromocytoma. All patients underwent abdominal computed
tomography and whole body 123I-MIBG scan to stage the disease. One hundred
healthy blood donors and 148 patients affected by essential hypertension were
enrolled as controls. Serum CgA and plasma MN were assayed by immunoradiometric
assay (IRMA) and high-performance liquid chromatography. Cut-off levels were
selected to obtain 99% specificity in healthy control subjects. RESULTS: Both MN
and CgA showed 95% sensitivity with comparable high specificity and diagnostic
accuracy (96% and 96% for CgA, 94% and 95% for MN, respectively). By employing
both markers and considering CgA or MN positivity, a 100% sensitivity was
obtained with 95% accuracy. MN and CgA concentration clearly increased from
controls to patients with pheochromocytomas (P<0.0001). A relationship between
serum CgA (but not MN) and tumor mass was found (P<0.0001). CONCLUSIONS: Both
markers are sensitive and specific in chromaffin-tumors detection: CgA IRMA assay
employed a simple and feasible technology and showed to be as sensitive and
slightly more accurate than MN.
PMID- 17043633
TI - Value of thyroglobulin to 131I uptake ratio in selection of initial therapy dose
of 131I in patients with differentiated thyroid carcinoma.
AB - AIM: To test the hypothesis that the ratio of thyroglobulin (Tg) to 131I uptake
in the thyroid bed during the immediate post-thyroidectomy work-up could be used
before first 131I treatment to detect patients with residual or metastatic
thyroid cancer and justify the administration of a higher ablation dose in
selected cases and a possibly better therapeutic effect. METHODS: We
retrospectively studied 293 patients with differentiated thyroid carcinoma that
received their first 131I treatment in our department. Patients with Tg >100
ng/mL, 131I uptake >10% and measurable Tg-specific autoantibodies, were excluded.
According to the post-therapy total body scan (TBS), we divided them in 2 groups:
group I, without metastases (negative TBS), and group II, with metastases
(positive TBS). The ratio of Tg to 131I uptake measured before the first 131I
treatment was calculated in both groups. RESULTS: A total of 248 patients were
included in the study; 225 in group I and 23 in group II. Tg to 131I uptake ratio
was significantly lower in group I (mean 2.17 ng/mL/%, range 0-36), than in group
II (mean 32.7 ng/mL/%, range 2.14-220), (P<0.01). The sensitivity, specificity
and accuracy (using a threshold ratio 7 ng/mL/% as normal) were all 95.6% for
predicting a positive post-therapy TBS. CONCLUSIONS: The use of a threshold ratio
7 ng/mL/% as the upper limit of normal provides useful information with higher
sensitivity and specificity in identifying patients with metastatic disease
creating the possibility for the selective use of higher initial iodine therapy
doses.
PMID- 17043634
TI - [186Re]HEDP in the palliation of painful bone metastases from cancers other than
prostate and breast.
AB - AIM: Palliative therapy using [186Re]hydroxyethylidene diphosphonate (HEDP) has
been widely tested in patients with bone metastases from prostate and breast
cancers. Whereas, to the best of our knowledge, only few cases of bone metastases
from tumors other than prostate and breast treated with [186Re]HEDP have been
reported. The aim of this paper is to report our experience with 186Re-HEDP in
the palliation of painful bone metastases from tumors other than prostate and
breast. METHODS: In this study 41 patients (17 non-small cell lung cancer-NSCLC,
1 small cell lung cancer, 1 lung neuroendocrine tumor, 8 bladder cancer, 3 kidney
cancer, 3 gastric cancer, 1 uterine carcinoma, 1 colon cancer, 1 rhinopharynx
carcinoma, 1 medullary thyroid carcinoma, 1 ovarian cancer, 1 esophagus cancer, 2
carcinoma of unknown origin) are evaluated. All patients had lesions with
increased [99mTc]MDP uptake and none had radiological findings of mainly
osteolytic lesions. A total of 46 therapeutic cycles were performed using a
[186Re]HEDP activity of 1 295 MBq for each administration. After treatment,
patients were followed up for 3 months or to the time of pain recurrence (if
longer than 3 months). Responses were evaluated using a validated method
considering the modifications of pain index, analgesic intake and performance
status. RESULTS: Treatment efficacy was complete in 49% (20/41) of patients,
partial in 36% (15/41) and negative in 15% (6/41). Namely, we observed 35% (6/17)
complete, 41% (7/17) partial and 24% (4/17) negative responses in patients with
NSCLC and 63% (5/8) complete, 25% (2/8) partial and 12% (1/8) negative responses
in patients affected by bladder cancer. The median duration of pain relief in
responder patients was 10 weeks. A mild platelet toxicity occurred in 32% (13/41)
of patients. CONCLUSIONS: Pain palliation with [186Re]HEDP seems highly effective
and safe also in patients with bone metastases from cancers other than prostate
and breast. Patients who can benefit from the treatment with [186Re]HEDP can be
selected on the basis of [99mTc]MDP bone scan and radiological examination
findings.
PMID- 17043635
TI - Iodine-131 pharmacokinetics in patients on hemodialysis for end stage renal
disease: clinical implications.
AB - AIM: Curative treatment of thyroid cancer is a major issue for patients with end
stage renal disease (ESRD) undergoing dialysis because they might not be included
in a renal transplant protocol once they have overcome this disease. Since 131I
is mostly eliminated by the kidneys, there is concern regarding the toxicity,
efficacy and feasibility of 131I-therapy of anuric dialyzed patients. METHODS:
This paper reports on 131I uptake and elimination from remnant thyroid tissue
(T), salivary glands (SG), stomach (S) and blood, after administration of 3.7 GBq
of 131I for 2 patients on twice weekly dialysis for ESRD. RESULTS: Compared to
normal renal function patients, radio-iodine recirculation is observed, and SG
and blood irradiation is about 6 times higher, but the dose delivered to the
thyroid is not significantly enhanced. Dialysis removes more 131I from SG, S and
blood than from T. Anticipated dialysis will reduce irradiation by 38% for the
blood, 45% for SG and 34% for T. CONCLUSIONS: Therefore, a higher 131I amount
could then be used, providing that accurate personalized dosimetry is previously
performed using 131I pharmacokinetic models. Concerning radiation protection
issues, no significant dialysis equipment contamination is noted, and nurses and
medical staff exposure remains below 0.2 mSv.
PMID- 17043636
TI - Diversity of TMPRSS2-ERG fusion transcripts in the human prostate.
AB - TMPRSS2-ERG gene fusions have recently been reported to be present in a high
proportion of human prostate cancers. In the current study, we show that great
diversity exists in the precise structure of TMPRSS2-ERG hybrid transcripts found
in human prostates. Fourteen distinct hybrid transcripts are characterized, each
containing different combinations of sequences from the TMPRSS2 and ERG genes.
The transcripts include two that are predicted to encode a normal full-length ERG
protein, six that encode N-terminal truncated ERG proteins and one that encodes a
TMPRSS2-ERG fusion protein. Interestingly, distinct patterns of hybrid
transcripts were found in samples taken from separate regions of individual
cancer-containing prostates, suggesting that TMPRSS2-ERG gene fusions may be
arising independently in different regions of a single prostate.
PMID- 17043637
TI - Urokinase receptor primes cells to proliferate in response to epidermal growth
factor.
AB - Epidermal growth factor (EGF) expresses mitogenic activity by a mechanism that
requires the EGF receptor (EGFR). We report that murine embryonic fibroblasts
(MEFs) proliferate in response to EGF only when these cells express the urokinase
receptor (uPAR). EGFR expression was equivalent in uPAR-/- and uPAR+/+ MEFs. In
response to EGF, these cells demonstrated equivalent overall EGFR tyrosine
phosphorylation and ERK/MAP kinase activation; however, phosphorylation of Tyr
845 in the EGFR, which has been implicated in cell growth, was substantially
decreased in uPAR-/- MEFs. STAT5b activation also was decreased. As Tyr-845 is a
c-Src target, we overexpressed c-Src in uPAR-/- MEFs and rescued EGF mitogenic
activity. Rescue also was achieved by expressing murine but not human uPAR,
suggesting a role for autocrine uPAR cell-signaling. In MDA-MB 231 breast cancer
cells, EGF mitogenic activity was blocked by uPAR gene silencing, with antibodies
that block uPA-binding to uPAR, and with a synthetic peptide that disrupts uPAR
dependent cell signaling. Again, c-Src overexpression rescued the mitogenic
activity of EGF. We conclude that uPAR-dependent cell-signaling may prime cells
to proliferate in response to EGF by promoting Tyr-845 phosphorylation and STAT5b
activation. The importance of this pathway depends on the c-Src level in the
cell.
PMID- 17043638
TI - The immunoglobulin heavy-chain gene 3' enhancers deregulate bcl-2 promoter usage
in t(14;18) lymphoma cells.
AB - In t(14;18) lymphomas, bcl-2 is juxtaposed to the immunoglobulin heavy-chain gene
(IgH), resulting in increased bcl-2 transcription and resistance to apoptosis.
Regulatory elements of both the bcl-2 promoter and the IgH enhancers are believed
to play a role in the increased expression of bcl-2 in t(14;18) lymphoma cells.
In addition, transcription of the translocated bcl-2 allele is deregulated with
activation of the normally minor bcl-2 P2 promoter. The mechanisms involved in
the promoter shift from P1 to P2 are not known. We found that the murine IgH 3'
enhancers increased bcl-2 P2 promoter activity in an episomal model of the
translocation, and IgH enhancer region HS12 had the greatest effect. Quantitative
chromatin immunoprecipitation (ChIP) assays revealed that localized histone H3
hyperacetylation of the P2 promoter was observed on the translocated allele in
t(14;18) DHL-4 cells and also on the stably transfected bcl-2 promoter-IgH
enhancer episomal construct. Analysis of the HS12 enhancer region revealed that a
previously identified nuclear factor-kappaB (NF-kappaB) site and a previously
uncharacterized downstream Cdx site, both of which are conserved in the human and
murine IgH enhancers, were important for its enhancer activity and promoter
activation. ChIP assays showed that C/EBPbeta bound to the HS12 Cdx site in vivo,
and mutation of this site abrogated the binding of C/EBPbeta. Reduced expression
of C/EBPbeta by transfection of small interfering RNA or interference with NF
kappaB activity decreased transcription from the bcl-2 promoters. These results
demonstrate that the IgH 3' enhancers, particularly HS12, are important for the
deregulation of bcl-2 promoter usage in t(14;18) lymphomas.
PMID- 17043639
TI - Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression
profiling.
AB - We have assessed the possibility to build a prognosis predictor (PP), based on
non-neoplastic mucosa microarray gene expression measures, for stage II colon
cancer patients. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10
with a metachronous metastasis, 14 with no recurrence) were profiled using the
Affymetrix HGU133A GeneChip. Patients were repeatedly and randomly divided into
1000 training sets (TSs) of size 16 and validation sets (VS) of size 8. For each
TS/VS split, a 70-gene PP, identified on the TS by selecting the 70 most
differentially expressed genes and applying diagonal linear discriminant
analysis, was used to predict the prognoses of VS patients. Mean prognosis
prediction performances of the 70-gene PP were 81.8% for accuracy, 73.0% for
sensitivity and 87.1% for specificity. Informative genes suggested branching
signal-transduction pathways with possible extensive networks between individual
pathways. They also included genes coding for proteins involved in immune
surveillance. In conclusion, our study suggests that one can build an accurate PP
for stage II colon cancer patients, based on non-neoplastic mucosa microarray
gene expression measures.
PMID- 17043640
TI - Human cancer cells require ATR for cell cycle progression following exposure to
ionizing radiation.
AB - The vast majority of cancer cells have defective checkpoints that permit the cell
cycle to progress in the presence of double-strand DNA breaks (DSBs) caused by
ionizing radiation (IR) and radiomimetic drugs. ATR (ataxia telangiectasia
mutated and Rad3-related) has recently been shown to be activated by DSBs,
although the consequences of this activity are largely unknown. In this report,
we use advanced gene targeting methods to generate biallelic hypomorphic ATR
mutations in human colorectal cancer cells and demonstrate that progression of
the cancer cell cycle after IR treatment requires ATR. Cells with mutant ATR
accumulated at a defined point at the beginning of the S phase after IR treatment
and were unable to progress beyond that point, whereas cells at later stages of
the S phase during the time of irradiation progressed and completed DNA
replication. The prolonged arrest of ATR mutant cancer cells did not involve the
ataxia telangiectasia mutated-dependent S-phase checkpoint, but rather closely
resembled a previously characterized form of cell cycle arrest termed S-phase
stasis. As ATR strongly contributed to clonogenic survival after IR treatment,
these data suggest that blocking ATR activity might be a useful strategy for
inducing S-phase stasis and promoting the radiosensitization of checkpoint
deficient cancer cells.
PMID- 17043641
TI - Regulation of clustered gene expression by cofactor of BRCA1 (COBRA1) in breast
cancer cells.
AB - Eucaryotic genes that are coordinately expressed tend to be clustered.
Furthermore, gene clusters across chromosomal regions are often upregulated in
various tumors. However, relatively little is known about how gene clusters are
coordinately expressed in physiological or pathological conditions. Cofactor of
BRCA1 (COBRA1), a subunit of the human negative elongation factor, has been shown
to repress estrogen-stimulated transcription of trefoil factor 1 (TFF1 or pS2) by
stalling RNA polymerase II. Here, we carried out a genome-wide study to identify
additional physiological target genes of COBRA1 in breast cancer cells. The study
identified a total of 134 genes that were either activated or repressed upon
small hairpin RNA-mediated reduction of COBRA1. Interestingly, many COBRA1
regulated genes reside as clusters on the chromosomes and have been previously
implicated in cancer development. Detailed examination of two such clusters on
chromosome 21 (21q22) and chromosome X (Xp11) reveals that COBRA1 is physically
associated with a subset of its regulated genes in each cluster. In addition,
COBRA1 was shown to regulate both estrogen-dependent and -independent
transcription of the gene cluster at 21q22, which encompasses the previously
identified COBRA1-regulated TFF1 (pS2) locus. Thus, COBRA1 plays a critical role
in the regulation of clustered gene expression at preferred chromosomal domains
in breast cancer cells.
PMID- 17043642
TI - P53 in blind subterranean mole rats--loss-of-function versus gain-of-function
activities on newly cloned Spalax target genes.
AB - A tumor suppressor gene, p53, controls cellular responses to a variety of stress
conditions, including DNA damage and hypoxia, leading to growth arrest and/or
apoptosis. Recently, we demonstrated that in blind subterranean mole rats,
Spalax, a model organism for hypoxia tolerance, the p53 DNA-binding domain
contains a specific Arg174Lys amino acid substitution. This substitution reduces
the p53 effect on the transcription of apoptosis genes (apaf1, puma, pten and
noxa) and enhances it on human cell cycle arrest and p53
stabilization/homeostasis genes (mdm2, pten, p21 and cycG). In the current study,
we cloned Spalax apaf1 promoter and mdm2 intronic regions containing consensus
p53-responsive elements. We compared the Spalax-responsive elements to those of
human, mouse and rat and investigated the transcriptional activity of Spalax and
human Arg174Lys-mutated p53 on target genes of both species. Spalax and human
mutated p53 lost induction of apaf1 transcription, and increased induction of
mdm2 transcription. We conclude that Spalax evolved hypoxia-adaptive mechanisms,
analogous to the alterations acquired by cancer cells during tumor development,
with a bias against apoptosis while favoring cell arrest and DNA repair.
PMID- 17043643
TI - Inhibition of NEMO, the regulatory subunit of the IKK complex, induces apoptosis
in high-risk myelodysplastic syndrome and acute myeloid leukemia.
AB - In high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML),
blasts constitutively activate the antiapoptotic transcription factor nuclear
factor-kappaB (NF-kappaB). Here, we show that this NF-kappaB activation relies on
the constitutive activation of the IkappaB kinase (IKK) complex, which is formed
by the IKKalpha, IKKbeta and IKKgamma/NF-kappaB essential modulator (NEMO)
subunits. A cell-permeable peptide that mimics the leucine zipper subdomain of
IKKgamma, thus preventing its oligomerization, inhibited the constitutive NF
kappaB activation and induced apoptotic cell death in a panel of human MDS and
AML cell lines (P39, MOLM13, THP1 and MV4-11). Small interfering RNA-mediated
knockdown of the p65 NF-kappaB subunit or the three IKK subunits including
IKKgamma/NEMO also induced apoptotic cell death in P39 cells. Cell death induced
by the IKKgamma/NEMO-antagonistic peptide involved the caspase-independent loss
of the mitochondrial transmembrane potential as well as signs of outer
mitochondrial membrane permeabilization with the consequent release of cytochrome
c, apoptosis-inducing factor and endonuclease G. Primary bone marrow CD34(+)
cells from high-risk MDS and AML patients also succumbed to the IKKgamma/NEMO
antagonistic peptide, but not to a mutated control peptide. Altogether, these
data indicate that malignant cells in high-risk MDS and AML cells critically
depend on IKKgamma/NEMO to survive. Moreover, our data delineate a novel
procedure for their therapeutic removal, through inhibition of IKKgamma/NEMO
oligomerization.
PMID- 17043644
TI - Pharmacologic inhibition of epigenetic modifications, coupled with gene
expression profiling, reveals novel targets of aberrant DNA methylation and
histone deacetylation in lung cancer.
AB - Lung cancer is the leading cause of cancer-related deaths in the United States
due, in large part, to the lack of early detection methods. Lung cancer arises
from a complex series of genetic and epigenetic changes leading to uncontrolled
cell growth and metastasis. Unlike genetic changes, epigenetic changes, such as
DNA methylation and histone acetylation, are reversible with currently available
pharmaceuticals and are early events in lung tumorigenesis detectable by non
invasive methods. In order to better understand how epigenetic changes contribute
to lung cancer, and to identify new disease biomarkers, we combined pharmacologic
inhibition of DNA methylation and histone deacetylation in non-small cell lung
cancer (NSCLC) cell lines, with genome-wide expression profiling. Of the more
than 200 genes upregulated by these treatments, three of these, neuronatin,
metallothionein 3 and cystatin E/M, were frequently hypermethylated and
transcriptionally downregulated in NSCLC cell lines and tumors. Interestingly,
four other genes, cylindromatosis, CD9, activating transcription factor 3 and
oxytocin receptor, were dominantly regulated by histone deacetylation and were
also frequently downregulated in lung tumors. The majority of these genes also
suppressed NSCLC growth in culture when ectopically expressed. This study
therefore reveals new putative NSCLC growth regulatory genes and epigenetic
disease biomarkers that may enhance early detection strategies and serve as
therapeutic targets.
PMID- 17043645
TI - Specific hypermethylation of LINE-1 elements during abnormal overgrowth and
differentiation of human placenta.
AB - In human post-natal somatic cells, low global levels of DNA methylation have been
associated with the hypomethylation of several repetitive elements, a feature
that has been proposed to be a surrogate epigenetic marker. These data, mainly
derived from the analysis of cancer cells, suggest a potential association
between loss of cell-growth control and altered differentiation with
hypomethylation of repetitive sequences. Partial hydatidiform moles (PHMs) can be
used as an alternative model for investigating this association in a non
tumorigenic context. This gestational disease is characterized by abnormal
overgrowth and differentiation of the placenta and spontaneous abortion. Here, we
comprehensively analyse the DNA methylation of these trophoblastic tissues in
both PHM and normal placenta at global and sequence-specific levels. Analysis of
the global 5-methylcytosine content and immunohistochemistry indicate that PHM
and normal placenta have identical global levels of DNA methylation. In contrast,
bisulfite genomic sequencing shows that, whereas Alu, NBL2 and satellite 2
repetitive elements are equally methylated, LINE-1 sequences are hypermethylated
in PHM tissues ( approximately 2-fold relative to normal placenta).
Interestingly, altered demethylation is also found in triploid diandric embryos
that originate from dispermic fertilization of an oocyte, a common event
responsible for most PHMs. In conclusion, alterations of DNA methylation do not
seem to be randomly distributed in PHM, as several repeated elements remain
unaltered, whereas LINE-1 sequences are hypermethylated. In addition, our
findings suggest that the hypomethylation of repetitive elements in cancer is
directly linked to the neoplasic process and not a simple consequence of loss of
growth control observed in most of the cancer cells.
PMID- 17043646
TI - No evidence for dual role of loss of heterozygosity in hereditary non-polyposis
colorectal cancer.
AB - Hereditary non-polyposis colorectal cancer (HNPCC) is caused by germline
mutations in mismatch repair (MMR) genes, mostly MLH1 and MSH2. Somatic
inactivation of the wild-type allele of the respective MMR gene is required for
tumor development. Unexpectedly, a recent study utilizing DNA from paraffin
embedded tissue material detected frequent loss of the mutant MMR gene allele in
HNPCC tumors. Dual role for loss of heterozygosity (LOH) was proposed. If somatic
loss of the wild-type MMR gene allele had occurred through point mutation or
promoter hypermethylation, frequent somatic deletions at the region of the MMR
gene locus, perhaps targeting other relevant cancer genes, could quite commonly
lead to loss of the mutant allele. To test this hypothesis, we studied a
population-based series of 25 fresh-frozen HNPCC tumors with a germline mutation
in MLH1 or MSH2 for LOH. Fourteen of the 25 tumors (56%) showed LOH at the
respective locus, and all 14 losses targeted the wild-type allele (P=0.00006).
These results strongly support the traditional two-hit model of HNPCC gene
inactivation.
PMID- 17043647
TI - Ionizing radiation activates IGF-1R triggering a cytoprotective signaling by
interfering with Ku-DNA binding and by modulating Ku86 expression via a p38
kinase-dependent mechanism.
AB - Ionizing radiation exposure results in the activation of several tyrosine kinase
receptors that participate in radiation-induced DNA damage response and
radioresistance. We previously showed that insulin-like growth factor 1 receptor
(IGF-1R) inhibition enhanced radiosensitivity of non-small-cell lung cancer
(NSCLC) cells. In this paper, we demonstrate that in U1810 NSCLC cells gamma
radiation activates IGF-1R within 10 min, with a maximal activation effect 2 h
post-irradiation. Impairment of IGF-1R tyrosine kinase activity enhances human
lung cancer cells radiosensitivity by a mechanism that involves
phosphatidylinositol 3-kinase (PI3-K) and p38 kinase. In an active form, IGF-1R
binds and activates p38 kinase, promoting receptor signaling. Conversely,
inhibition of IGF-1R phosphorylation results in IGF-1R/p38 complex disruption and
p38 kinase inactivation. We have also demonstrated that in insulin-like growth
factor-1-stimulated cells, Ku-DNA-binding activation is induced by ionizing
radiation within 4 h, reaches a maximum level at 12 h and remains active up to 72
h. Blockade of IGF-1R activity or its downstream signaling through p38 kinase
induces a decrease in radiation-mediated Ku-DNA-binding activation and
downregulates the level of Ku86, without affecting Ku70 expression in the nucleus
of U1810 cells. The IGF-1R signaling via PI3-K does not interfere with the p38
signaling, the Ku-DNA-binding activity or the level of Ku86. Our present study
demonstrates for the first time that ionizing radiation activates IGF-1R.
Inhibition of IGF-1R signaling via p38 kinase induces radiosensitivity by a novel
mechanism involving nuclear Ku86.
PMID- 17043648
TI - Tissue transglutaminase expression promotes cell attachment, invasion and
survival in breast cancer cells.
AB - Distant metastasis is frequently observed in patients with breast cancer and is a
major cause of cancer-related deaths in these patients. Currently, very little is
known about the mechanisms that underlie the development of the metastatic
phenotype in breast cancer cells. We previously found that metastatic breast
cancer cells express high levels of tissue transglutaminase (TG2), but
established no direct link between TG2 and metastasis. In this study, we
hypothesized that TG2 plays a role in conferring the metastatic phenotype to
breast cancer cells. The results obtained suggested that increased expression of
TG2 in breast cancer cells contributes to their increased survival, invasion and
motility. We further found that TG2 protein in a metastatic breast cancer MDA
MB231 cells was present on the cell surface in close association with integrins
beta1, beta4 and beta5. Downregulation of endogenous TG2 by small interfering RNA
inhibited fibronectin (Fn)-mediated cell attachment, survival and invasion.
Conversely, ectopic expression of TG2 augmented invasion of breast cancer cells
and attachment to Fn-coated surfaces. We conclude that TG2 expression in breast
cancer cells plays an important role in the development of the metastatic
phenotype.
PMID- 17043649
TI - Apoptosis and erythroid differentiation triggered by Bcr-Abl inhibitors in CML
cell lines are fully distinguishable processes that exhibit different sensitivity
to caspase inhibition.
AB - Imatinib targets the Bcr-Abl oncogene that causes chronic myelogenous leukemia
(CML) in humans. Recently, we demonstrated that besides triggering apoptosis in
K562 cells, imatinib also mediated their erythroid differentiation. Although both
events appear to proceed concomitantly, it is not known at present whether or not
imatinib-induced apoptosis and differentiation are interdependent processes.
Hence, we investigated the requirements for Bcr-Abl inhibitor-mediated apoptosis
and erythroid differentiation in several established and engineered CML cell
lines. Imatinib triggered apoptosis and erythroid differentiation of different
CML cell lines, but only apoptosis exhibited sensitivity to ZVAD-fmk inhibition.
Conversely, the p38 mitogen-activated protein (MAP) kinase inhibitor, SB202190,
significantly slowed down erythroid differentiation without affecting caspase
activation. Furthermore, imatinib and PD166326, another Bcr-Abl inhibitory
molecule, triggered erythroid differentiation of K562 cell clones, nevertheless
resistant to Bcr-Abl inhibitor-induced apoptosis. Finally, short hairpin RNA
inhibitor (shRNAi) silencing of caspase 3 efficiently inhibited caspase activity
but had no effect on erythroid differentiation, whereas silencing of Bcr-Abl
mimicked imatinib or PD166326 treatment, leading to increased apoptosis and
erythroid differentiation of K562 cells. Taken together, our findings not only
demonstrate that Bcr-Abl inhibitor-mediated apoptosis and differentiation are
fully distinguishable events, but also that caspases are dispensable for
erythroid differentiation of established CML cell lines.
PMID- 17043650
TI - GSK3 beta mediates suppression of cyclin D2 expression by tumor suppressor PTEN.
AB - PTEN, encoding a lipid phosphatase, is a tumor suppressor gene and is mutated in
various types of cancers. It is reported to regulate G1 to S phase transition of
the cell cycle by influencing the expression, protein stability and subcellular
location of cyclin D1. Here, we provide evidence that PTEN modulates the
transcription and protein stability of cyclin D2. Targeted deletion of Pten in
mouse embryonic fibroblasts (MEFs) endowed cells with greater potential to
overcome G1 arrest than wild-type MEFs and led to the elevated expression of
cyclin D2, which was suppressed by the introduction of PTEN. We further defined a
pathway involving GSK3beta and beta-catenin/TCF in PTEN-mediated suppression of
cyclin D2 transcription. LiCl, an inhibitor of GSK3beta, abolished inhibitory
effect of PTEN on cyclin D2 expression, and TCF members could directly bind to
the promoter of cyclin D2 and regulate its transcription in a CREB-dependent
manner. Our results indicate that the downregulation of cyclin D2 expression by
PTEN is mediated by the GSK3beta/beta-catenin/TCF pathway in cooperation with
CREB, and suggest a convergence from the PI-3 kinase/PTEN pathway and the Wnt
pathway in modulation of cyclin D2 expression.
PMID- 17043651
TI - A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma
cells both in vitro and in vivo.
AB - Signal transducer and activator of transcription-3 (STAT3) is constitutively
activated in a variety of cancer types, including malignant gliomas. STAT3 is
activated by phosphorylation of a tyrosine residue, after which it dimerizes and
translocates into the nucleus. There it regulates the expression of several genes
responsible for proliferation and survival at the transcriptional level. A
selective inhibitor of STAT3 phosphorylation, AG490, has been shown to inhibit
growth and induce apoptosis in some cancer cell types. However, although AG490
routinely shows in vitro anticancer activity, it has not consistently
demonstrated an in vivo anticancer effect in animal models. Here, we have tested
WP1066, a novel inhibitor structurally related to AG490 but significantly more
potent and active, against human malignant glioma U87-MG and U373-MG cells in
vitro and in vivo. IC(50) values for WP1066 were 5.6 muM in U87-MG cells and 3.7
muM in U373-MG cells, which represents 18-fold and eightfold increases in
potency, respectively, over that of AG490. WP1066 activated Bax, suppressed the
expression of c-myc, Bcl-X(L) and Mcl-1, and induced apoptosis. Systemic
intraperitoneal administration of WP1066 in mice significantly (P<0.001)
inhibited the growth of subcutaneous malignant glioma xenografts during the 30
day follow-up period. Immunohistochemical analysis of the excised tumors revealed
that phosphorylated STAT3 levels in the WP1066 treatment group remained inhibited
at 3 weeks after the final WP1066 injection, whereas tumors from the control
group expressed high levels of phosphorylated STAT3. We conclude that WP1066
holds promise as a therapeutic agent against malignant gliomas.
PMID- 17043652
TI - Tumor progression induced by the loss of E-cadherin independent of beta
catenin/Tcf-mediated Wnt signaling.
AB - E-cadherin-mediated cell-cell adhesion is frequently lost during the development
of malignant epithelial cancers. Employing a transgenic mouse model of beta-cell
carcinogenesis (Rip1Tag2) we have previously shown that the loss of E-cadherin is
a rate-limiting step in the progression from adenoma to carcinoma. However, the
mere loss of cell adhesion may not be sufficient and additional signals are
required to cause tumor cells to permeate the basal membrane and to invade
surrounding tissue. Besides being an important component of the E-cadherin cell
adhesion complex, beta-catenin plays a critical role in canonical Wnt signaling.
We report here that beta-catenin-mediated Wnt signaling does not contribute to
tumor progression in Rip1Tag2 mice. E-cadherin downregulates beta-catenin/Tcf
mediated transcriptional activity by sequestrating beta-catenin into E-cadherin
cell-adhesion complexes even in the presence of activated Wnt signaling. Upon
loss of E-cadherin expression, beta-catenin is degraded and Tcf/beta-catenin
mediated transcriptional activity is not induced. Moreover, forced expression of
constitutive-active beta-catenin or genetic ablation of Tcf/beta-catenin
transcriptional activity in tumor cells of Rip1Tag2 transgenic mice does not
affect tumor progression. Together, the data indicate that signals other than
beta-catenin/Tcf-mediated Wnt signaling are induced by the loss of E-cadherin
during tumor progression in Rip1Tag2 transgenic mice.
PMID- 17043653
TI - AKT induces senescence in primary esophageal epithelial cells but is permissive
for differentiation as revealed in organotypic culture.
AB - Epidermal growth factor receptor (EGFR) overexpression and activation is critical
in the initiation and progression of cancers, especially those of epithelial
origin. EGFR activation is associated with the induction of divergent signal
transduction pathways and a gamut of cellular processes; however, the cell-type
and tissue-type specificity conferred by certain pathways remains to be
elucidated. In the context of the esophageal epithelium, a prototype stratified
squamous epithelium, EGFR overexpression is relevant in the earliest events of
carcinogenesis as modeled in a three-dimensional organotypic culture system. We
demonstrate that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway,
and not the MEK/MAPK (mitogen-activated protein kinase) pathway, is
preferentially activated in EGFR-mediated esophageal epithelial hyperplasia, a
premalignant lesion. The hyperplasia was abolished with direct inhibition of PI3K
and of AKT but not with inhibition of the MAPK pathway. With the introduction of
an inducible AKT vector in both primary and immortalized esophageal epithelial
cells, we find that AKT overexpression and activation is permissive for complete
epithelial formation in organotypic culture, but imposes a growth constraint in
cells grown in monolayer. In organotypic culture, AKT mediates changes related to
cell shape and size with an expansion of the differentiated compartment.
PMID- 17043654
TI - The tumour-suppressor Scribble dictates cell polarity during directed epithelial
migration: regulation of Rho GTPase recruitment to the leading edge.
AB - Altered expression of human Scribble is associated with invasive epithelial
cancers, however, its role in tumour development remains unclear. Mutations in
Drosophila Scribble result in loss of polarity, overproliferation and 3D
tumourous overgrowth of epithelial cells. Using complementation studies in
Drosophila we recently demonstrated that expression of human Scribble can also
regulate polarity and restrict tissue overgrowth. Here, we have undertaken a
detailed study of human Scribble function in the polarized mammary cell line,
MCF10A. We show that although Scribble does not seem to be required for apical
basal polarity or proliferation control in MCF10A cells, Scribble is essential
for the control of polarity associated with directed epithelial cell migration.
Scribble-depleted MCF10A cells show defective in vitro wound closure and
chemotactic movement. The cells at the wound edge fail to polarize, show reduced
lamellipodia formation and impaired recruitment of Cdc42 and Rac1 to the leading
edge. Furthermore, we show that this function is relevant in vivo as Scribble
mutant mice show defective epidermal wound healing. This data identifies an
essential role for mammalian Scribble in the regulation of the polarity
specifically involved in directed epithelial migration.
PMID- 17043655
TI - Collagen type I-induced Smad-interacting protein 1 expression downregulates E
cadherin in pancreatic cancer.
AB - Pancreatic cancer is a devastating disease with poor prognosis. Production of
large quantities of extracellular matrix and early metastasis are characteristics
of this disease. One important step in the development of various cancers is the
loss of E-cadherin gene expression or inactivation of E-cadherin mediated cell
cell adhesion. It has been shown that collagen type I promotes downregulation of
E-cadherin expression, which correlates with enhanced cell migration and
invasiveness. In this context, we elucidated the role of Smad-interacting protein
1 (SIP1), which has been discussed as a negative regulator of E-cadherin gene
expression. We demonstrate that SIP1 upregulation shows an inverse relationship
with E-cadherin in advanced pancreatic tumour stages. In Panc-1 cells, SIP1
expression can be induced by exposure to collagen type I in a src-dependent
manner. In addition, overexpression of SIP1 reduces E-cadherin mRNA and protein
levels. Taken together, these results suggest that SIP1 is involved in the
progression of pancreatic cancer and plays a role in mediating signal
transduction from collagen type I to downregulate E-cadherin expression.
PMID- 17043656
TI - The p85 regulatory subunit of PI3K mediates TSH-cAMP-PKA growth and survival
signals.
AB - Phosphatidylinositol 3-kinase (PI3K) is necessary for thyroid stimulating hormone
(TSH)-induced cell cycle progression. To determine the molecular mechanism
linking PI3K to TSH, we have identified a serine residue in p85alpha(PI3K)
phosphorylated by protein kinase A (PKA) in vitro and in vivo. Expression of an
alanine mutant (p85A) abolished cyclic AMP/TSH-induced cell cycle progression and
was lethal in thyroid cells (FRTL-5). The aspartic version of the p85alpha(PI3K)
(p85D) inhibited apoptosis following TSH withdrawal. The p85alpha(PI3K) wild type
not the p85A bound PKA regulatory subunit RIIbeta in cells stimulated with cAMP
or TSH. The binding of the aspartic version of p85alpha(PI3K) to RIIbeta was
independent of cAMP or TSH stimulation. Similarly, binding of PI3K to p21Ras and
activation of AKT, a downstream PI3K target, were severely impaired in cells
expressing the p85A mutant. Finally, we found that the catalytic activity of PI3K
was stimulated by TSH in cells expressing the wild-type p85alpha(PI3K) but not in
cells expressing p85A. This latter mutant did not affect the epidermal growth
factor-stimulated PI3K activity. We suggest that (1) TSH-cAMP-induced PKA
phosphorylates p85alpha(PI3K) at serine 83, (2) phosphorylated p85alpha(PI3K)
binds RIIbeta-PKA and targets PKAII to the membrane, and (3) PI3K activity and
p21Ras binding to PI3K increase and activate PI3K downstream targets. This
pathway is essential for the transmission of TSH-cAMP growth signals.
PMID- 17043657
TI - Periostin promotes invasiveness and resistance of pancreatic cancer cells to
hypoxia-induced cell death: role of the beta4 integrin and the PI3k pathway.
AB - Pancreatic ductal adenocarcinoma is a devastating disease, characterized by a
rapid progression and poor treatment response. Using gene expression profiling of
pancreatic cancer tissues, we previously identified periostin as a potential
diagnostic and therapeutic target. In this study, we report the overexpression of
periostin in a larger set of pancreatic cancer tissues and show that although the
periostin transcript is exclusively expressed in tumour cells, the protein
product is only detected in the extracellular matrix adjacent to cancer cells.
Using an enzyme-linked immunosorbent assay (ELISA) assay, we show significantly
increased levels of periostin in the sera of pancreatic cancer patients compared
to non-cancer controls. We demonstrate that periostin promotes the invasiveness
of tumour cells by increasing the motility of cells without inducing expression
of proteases, and enhances the survival of tumour cells exposed to hypoxic
conditions. At the molecular level, we provide evidence that the alpha(6)beta(4)
integrin complex acts as the cell receptor of periostin in pancreatic cancer
cells and that interaction promotes phosphorylation of focal adhesion kinase
(FAK) and protein kinase B (AKT) though activation of the PI3 kinase pathway, but
not the RAS/MEK/ERK pathway. These findings suggest an important role of
periostin in pancreatic cancer and provide a rationale to study periostin for
diagnostic and therapeutic applications.
PMID- 17043658
TI - Role of hypoxia inducible factor-1 alpha in modulation of apoptosis resistance.
AB - Hypoxia inducible factor-1 (HIF-1) is the major transcription factor and key
regulator of adoptive responses to hypoxia. Although it usually promotes tumor
cell survival under hypoxia, it has also been implied to trigger apoptosis.
Although the impact of hypoxia has been extensively studied in many adult solid
tumors, its role in most childhood tumors, for example, in rhabdomyosarcoma (RMS)
or Ewing sarcoma (ES), has not yet been addressed. Here, we report that hypoxia
protects A204 RMS and A673 ES cells against anticancer drug- or tumor necrosis
factor-related apoptosis-inducing ligand-induced apoptosis and that Hif-1alpha
plays a key role in conferring apoptosis resistance under hypoxia. Although a
functional HIF-1 pathway and proapoptotic proteins such as p53 and Bcl-2/E1B 19
kDa interacting protein 3 were activated under hypoxia in both A204 RMS and A673
ES cells, these cells remained refractory to apoptosis. Concomitant analysis of
antiapoptotic proteins revealed that hypoxia induced expression of Bcl-2 and
inhibitor of apoptosis proteins (IAP)-2 as well as proteins associated with
anaerobic metabolism such as the glucose transporter protein GLUT-1 and the
glycolytic enzyme Aldolase A. Specific downregulation of Hif-1alpha by RNA
interference significantly enhanced apoptosis under hypoxia by preventing the
hypoxia-mediated increase in GLUT-1 expression without altering expression levels
of the antiapoptotic proteins Bcl-2 or cIAP-2. Moreover, glucose deprivation
induced apoptosis of A204 RMS and A673 ES cells was inhibited under hypoxic
conditions in a Hif-1alpha-dependent manner. As GLUT-1 was induced via Hif-1alpha
under hypoxia in A204 RMS and A673 ES, these findings suggest that the Hif-1alpha
mediated increase in glucose uptake plays an important role in conferring
apoptosis resistance. Thus, hypoxia-inducible genes may represent novel targets
for therapeutic intervention in some pediatric tumors, which warrants further
investigation.
PMID- 17043659
TI - E2F4 regulates a stable G2 arrest response to genotoxic stress in prostate
carcinoma.
AB - The retinoblastoma (pRB) family proteins regulate the E2F transcription factors;
their complexes regulate critical transitions through the cell cycle. The
function of these pRB family/E2F complexes, which includes p130/E2F4, in response
to genotoxic agents, is not well understood. We investigated the role of E2F4 in
the genotoxic stress response. Following radiation treatment, E2F4 colocalized
with p130 in the nucleus during a radiation-induced stable G(2)-phase arrest.
Arrested cells had significantly decreased expression of Cyclins A2 and B1 and
decreased phosphorylation of mitotic protein monoclonal-2 (MPM-2) mitotic
proteins. Small interference RNA (siRNA)-mediated knockdown of E2F4 sensitized
cells to subsequent irradiation, resulting in enhanced cellular DNA damage and
cell death, as determined by caspase activation and decreased clonogenic cell
survival. Downstream E2F4 targets potentially involved in the progression from
G(2) into M phase were identified by oligonucleotide microarray expression
profiling. Chromatin immunoprecipitation localized E2F4 at promoter regions of
the Bub3 and Pttg1 mitotic genes following irradiation, which were among the
downregulated genes identified by the microarray. These data suggest that in
response to radiation, E2F4 becomes active in the nucleus, enforces a stable G(2)
arrest by target gene repression, and thus provides increased cell survival
ability by minimizing propagation of cells that have irreparable DNA damage.
PMID- 17043660
TI - Snail silencing effectively suppresses tumour growth and invasiveness.
AB - The transcription factor Snail has been recently proposed as an important
mediator of tumour invasion because of its role in downregulation of E-cadherin
and induction of epithelial-mesenchymal transitions (EMT). This behaviour has led
to the consideration of Snail as a potential therapeutic target to block tumour
progression. In this report, we provide evidence for this hypothesis. We show
that silencing of Snail by stable RNA interference in MDCK-Snail cells induces a
complete mesenchymal to epithelial transition (MET), associated to the
upregulation of E-cadherin, downregulation of mesenchymal markers and inhibition
of invasion. More importantly, stable interference of endogenous Snail in two
independent carcinoma cell lines leads to a dramatic reduction of in vivo tumour
growth, accompanied by increased tumour differentiation and a significant
decrease in the expression of MMP-9 and angiogenic markers and invasiveness.
These results indicate that use of RNA interference can be an effective tool for
blocking Snail function, opening the way for its application in new antiinvasive
therapies.
PMID- 17043661
TI - A small molecule based on the pRb2/p130 spacer domain leads to inhibition of cdk2
activity, cell cycle arrest and tumor growth reduction in vivo.
AB - One strategy in the development of anticancer therapeutics has been to arrest
malignant proliferation through inhibition of the enzymatic activity of cyclin
dependent kinases (cdks), which are key regulatory molecules of the cell cycle.
Over the past few years, numerous compounds with remarkable cdk inhibitory
activity have been studied in cancer therapy, although it is very difficult to
point out the best cdk to target. An excellent candidate appears to be cdk2,
whose alteration is a pathogenic hallmark of tumorigenesis. The small molecule
described in our study showed an inhibitory effect on the kinase activity of
cdk2, a significant growth arrest observed in a colony formation assay and a
reduction in the size of the tumor in nude mice, thus suggesting its potential
role as a promising new type of mechanism-based antitumor drug, also for the
treatment of hyperproliferative disorders.
PMID- 17043662
TI - Identification of molecular markers and signaling pathway in endometrial cancer
in Hong Kong Chinese women by genome-wide gene expression profiling.
AB - Endometrial cancer is the third most common gynecologic malignancy and the ninth
most common malignancy for females overall in Hong Kong. Approximately 80% or
more of these cancers are endometrioid endometrial adenocarcinomas. The aim of
this study was to reveal genes contributing to the development of endometrioid
endometrial cancer, which may impact diagnosis, prognosis and treatment of the
disease. Whole-genome gene expression analysis was completed for a set of 55
microdissected sporadic endometrioid endometrial adenocarcinomas and 29
microdissected normal endometrium specimens using the Affymetrix Human U133 Plus
2.0 oligonucleotide microarray. Selected genes of interest were validated by
quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was
performed to reveal gene interactions involved in endometrial tumorigenesis.
Unsupervised hierarchical clustering displayed a distinct separation between the
endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis
identified 117 highly differentially regulated genes (>or=4.0-fold change), which
distinguished the endometrial cancer specimens from normal endometrium. Twelve
novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5,
BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and
further validated in an independent set of 56 cancer and 29 normal samples using
qRT-PCR. In addition, 10 genes were differentially regulated in late-stage
cancer, as compared to early-stage disease, and may be involved in tumor
progression. Pathway analysis of the expression data from this tumor revealed an
interconnected network consisting of 21 aberrantly regulated genes involved in
angiogenesis, cell proliferation and chromosomal instability. The results of this
study highlight the molecular features of endometrioid endometrial cancer and
provide insight into the events underlying the development and progression of
endometrioid endometrial cancer.
PMID- 17043663
TI - Proteomic identification of the wt-p53-regulated tumor cell secretome.
AB - Tumor-stroma interactions play a major role in tumor development, maintenance and
progression. Yet little is known on how the genetic alterations that underlie
cell transformation elicit cell extrinsic changes modulating heterotypic cell
interactions. We hypothesized that these events involve a modification in the
complement of secreted proteins by the cell, acting as mediators of intercellular
communication. To test this hypothesis, we examined the role of wt-p53, a major
tumor suppressor, on the tumor microenvironment through its regulation of
secreted factors. Using a combination of 2-DE and cICAT proteomic techniques, we
found a total of 111 secreted proteins, 39 of which showed enhanced and 21
inhibited secretion in response to wt-p53 expression. The majority of these were
not direct targets of p53 transcription factor activity, suggesting a novel role
for wt-p53 in the control of intracellular protein trafficking and/or secreted
protein stability. Evidence for p53-controlled post-translational modifications
on nine secreted proteins was also found. These findings will enhance our
understanding of wt-p53 modulated interactions of the tumor with its environment.
PMID- 17043664
TI - Expression and localization of PDGF-B, PDGF-D, and PDGF receptor in the kidney of
angiotensin II-infused rat.
AB - Lipid accumulation in the kidney is a marker of tissue damage and may play a role
in the development of renal injury. We have previously shown that long-term
administration of angiotensin II in rats causes increased expression of
transforming growth factor-beta1, coupled with an accumulation of lipids in the
tubular and vascular wall cells in the kidney. In this study, we examine the
regulation of expression of platelet-derived growth factor (PDGF) and its
receptor system and their co-localization with lipid deposits in the kidneys of
angiotensin II-infused rats. Real-time RT-PCR showed that expression of PDGF-B,
PDGF-D, and PDGF receptor-beta (PDGFR-beta) mRNA was increased by angiotensin II
infusion, and in situ hybridization showed the co-localization of these mRNAs.
Tubular cells that had increased PDGF-B mRNA expression were positive for lipid
deposition and also for cellular proliferation, which was indicated by the
presence of proliferating cell nuclear antigen. By contrast, in the kidneys of
angiotensin II-infused rats, apoptosis occurred in tubular cells that contained
deposits of iron but not lipids. The deposition of lipids and upregulation of
PDGF-B, PDGF-D, and PDGFR-beta induced by administration of angiotensin II were
all suppressed by the selective angiotensin II type 1 (AT(1)) receptor antagonist
losartan, but not by the nonspecific vasodilator hydralazine. The findings that
lipid accumulation, upregulation of PDGF-B, PDGF-D, and PDGFR-beta, and cellular
proliferation were topologically associated and regulated in an AT(1) receptor
dependent manner in the kidney of angiotensin II-infused rats suggests that these
phenomena are related.
PMID- 17043665
TI - DNA methylation-dependent silencing of CST6 in human breast cancer cell lines.
AB - Cystatin M (CST6) is a candidate breast cancer tumor suppressor that is expressed
in normal and premalignant breast epithelium, but not in metastatic breast cancer
cell lines. CST6 is subject to epigenetic silencing in MCF-7 breast cancer cells
related to methylation of the CpG island that encompasses the CST6 proximal
promoter region and exon 1. In the current study, CST6 CpG island methylation and
expression status was examined in a panel of breast cancer cell lines. Seven of
12 (58%) cell lines lack detectable expression of CST6 and treatment of these
cells with 5-aza-2'-deoxycytidine resulted in a significant increase in CST6
expression, suggesting that the loss of expression may be related to methylation
dependent epigenetic silencing. Bisulfite sequencing of CST6 in a subset of
breast cancer cell lines revealed CpG island hypermethylation in CST6-negative
cells, and an absence of CpG island methylation in cells that express CST6. The
extent of regional methylation was strongly associated with the lack of
expression of CST6 among these cell lines. In particular, hypermethylation of the
proximal promoter was significantly associated with CST6 gene silencing, and
methylation of a number of individual CpGs was found to be statistically
correlated with extinction of gene expression. These results establish a strong
link between CST6 promoter hypermethylation and loss of CST6 expression in breast
cancer cell lines, and suggest that methylation-dependent epigenetic silencing of
CST6 may represent an important mechanism for loss of CST6 during breast
carcinogenesis in vivo.
PMID- 17043666
TI - Inhibition of EGFR signaling abrogates smooth muscle proliferation resulting from
sustained distension of the urinary bladder.
AB - Urinary bladder outlet obstruction results in sustained stretch of the detrusor
muscle and can lead to pathological smooth muscle hyperplasia and hypertrophy.
The epidermal growth factor receptor (EGFR) is a cognate receptor for mitogens
implicated in bladder hyperplasia/hypertrophy. Here, we investigated the
potential for modulation of this pathway by pharmacologic targeting with a
clinically available EGFR antagonist using an organ culture model of bladder
stretch injury as a test system. Urinary bladders from adult female rats were
distended in vivo with medium containing the EGFR inhibitor ZD1839 (gefitinib,
Iressa). The bladders were excised and incubated in ex vivo organ culture for 4
24 h. EGFR phosphorylation, DNA proliferation, and the extent of apoptosis in the
cultured tissues were assessed. To verify that the smooth muscle cells (SMC) are
a target of the EGFR inhibitor, primary culture human and rat bladder SMC were
subjected to cyclic mechanical stretch in vitro in the presence of ZD1839. Levels
of phosphorylated EGFR were significantly increased in the detrusor muscle with
12 h of stretch in the organ cultures. This activation coincided with a
subsequent 23-fold increase in DNA synthesis and a 30-fold decrease in apoptosis
in the muscle compartment at 24 h. In the presence of ZD1839, DNA synthesis was
reduced to basal levels without an increase in the rate of apoptosis under ex
vivo conditions. Mechanical stretch of bladder SMC in vitro resulted in a
significant increase in DNA synthesis, which was completely abrogated by
treatment with ZD1839 but not by AG825, an inhibitor of the related receptor,
ErbB2. Our results indicate that the EGFR pathway is a physiologically relevant
signaling mechanism in hypertrophic bladder disease resulting from mechanical
distension and may be amenable to pharmacologic intervention.
PMID- 17043667
TI - Comparison of lymphoblast mitochondria from normal subjects and patients with
Barth syndrome using electron microscopic tomography.
AB - Barth syndrome (BTHS) is a mitochondrial disorder that is caused by mutations in
the tafazzin gene, which affects phospholipid composition. To determine whether
this defect leads to alterations in the internal three-dimensional organization
of mitochondrial membranes, we applied electron microscopic tomography to
lymphoblast mitochondria from BTHS patients and controls. Tomograms were formed
from 50 and 150 nm sections of chemically fixed lymphoblasts and the data were
used to manually segment volumes of relevant structural details. Normal
lymphoblast mitochondria contained well-aligned, lamellar cristae with slot-like
junctions to the inner boundary membrane. In BTHS, mitochondrial size was more
variable and the total mitochondrial volume per cell increased mainly due to
clusters of fragmented mitochondria inside nuclear invaginations. However,
mitochondria showed reduced cristae density, less cristae alignment, and
inhomogeneous cristae distribution. Three-dimensional reconstruction of BTHS
mitochondria revealed zones of adhesion of the opposing inner membranes, causing
obliteration of the intracrista space. We found small isolated patches of
adhesion as well as extended adhesion zones, resulting in sheets of collapsed
cristae packaged in multiple concentric layers. We also found large tubular
structures (diameter 30-150 nm) that appeared to be derivatives of the adhesion
zones. The data suggest that mitochondrial abnormalities of BTHS involve
adhesions of inner mitochondrial membranes with subsequent collapse of the
intracristae space.
PMID- 17043669
TI - In vivo evidence that 5-HT(2C) receptors inhibit 5-HT neuronal activity via a
GABAergic mechanism.
AB - BACKGROUND AND PURPOSE: Recent evidence suggests that 5-HT(2C) receptor
activation may inhibit midbrain 5-HT neurones by activating neighbouring GABA
neurones. This hypothesis was tested using the putative selective 5-HT(2C)
receptor agonist, WAY 161503. EXPERIMENTAL APPROACH: The effect of WAY 161503 on
5-HT cell firing in the dorsal raphe nucleus (DRN) was investigated in
anaesthetised rats using single unit extracellular recordings. The effect of WAY
161503 on DRN GABA neurones was investigated using double label
immunohistochemical measurements of Fos, glutamate decarboxylase (GAD) and 5
HT(2C) receptors. Finally, drug occupancy at 5-HT(2A) receptors was investigated
using rat positron emission tomography and ex vivo binding studies with the 5
HT(2A) receptor radioligand [(11)C]MDL 100907. KEY RESULTS: WAY 161503 caused a
dose-related inhibition of 5-HT cell firing which was reversed by the 5-HT(2)
receptor antagonist ritanserin and the 5-HT(2C) receptor antagonist SB 242084 but
not by the 5-HT(1A) receptor antagonist WAY 100635. SB 242084 pretreatment also
prevented the response to WAY 161503. The blocking effects of SB 242084 likely
involved 5-HT(2C) receptors because the drug did not demonstrate 5-HT(2A)
receptor occupancy in vivo or ex vivo. The inhibition of 5-HT cell firing induced
by WAY 161503 was partially reversed by the GABA(A) receptor antagonist
picrotoxin. Also, WAY 161503 increased Fos expression in GAD positive DRN
neurones and DRN GAD positive neurones expressed 5-HT(2C) receptor
immunoreactivity. CONCLUSIONS AND IMPLICATIONS: These findings indicate that WAY
161503 inhibits 5-HT cell firing in the DRN in vivo, and support a mechanism
involving 5-HT(2C) receptor-mediated activation of DRN GABA neurones.
PMID- 17043670
TI - The MC4 receptor and control of appetite.
AB - Mutations in the human melanocortin (MC)4 receptor have been associated with
obesity, which underscores the relevance of this receptor as a drug target to
treat obesity. Infusion of MC4R agonists decreases food intake, whereas
inhibition of MC receptor activity by infusion of an MC receptor antagonist or
with the inverse agonist AgRP results in increased food intake. This review
addresses the role of the MC system in different aspects of feeding behaviour.
MC4R activity affects meal size and meal choice, but not meal frequency, and the
type of diet affects the efficacy of MC4R agonists to reduce food intake. The
central sites involved in the different aspects of feeding behaviour that are
affected by MC4R signalling are being unravelled. The paraventricular nucleus
plays an important role in food intake per se, whereas MC signalling in the
lateral hypothalamus is associated with the response to a high fat diet. MC4R
signalling in the brainstem has been shown to affect meal size. Further genetic,
behavioural and brain-region specific studies need to clarify how the MC4R
agonists affect feeding behaviour in order to determine which obese individuals
would benefit most from treatment with these drugs. Application of MCR agonists
in humans has already revealed side effects, such as penile erections, which may
complicate introduction of these drugs in the treatment of obesity.
PMID- 17043672
TI - Characterization of the snake venom ligand [125I]-DNP binding to natriuretic
peptide receptor-A in human artery and potent DNP mediated vasodilatation.
AB - BACKGROUND AND PURPOSE: The natriuretic peptides, ANP and BNP, modulate vascular
smooth muscle tone in human conduit arteries. Surprisingly, the natriuretic
peptide receptor-A (NPR-A) has not been visualized using radioligand binding in
these vessels. A new member of this peptide family, Dendroaspis natriuretic
peptide (DNP) identified from snake venom, has been proposed to be present in
human plasma and endothelial cells. Also, recently a novel radioligand, [(125)I]
DNP, has been characterized as selective for NPR-A in human heart. EXPERIMENTAL
APPROACH: Our aims were to investigate expression and function of NPR-A receptors
in human mammary artery using [(125)I]-DNP to quantify receptor density,
immunocytochemistry to delineate the cellular distribution of the receptor and in
vitro pharmacology to compare DNP induced vasodilatation to that of ANP. KEY
RESULTS: Saturable, sub-nanomolar affinity [(125)I]-DNP binding was detected to
smooth muscle of mammary artery, with receptor density of approximately 2 fmol
mg(-1) protein, comparable to that of other vasoactive peptides. NPR-A
immunoreactivity was localised to vascular smooth muscle cells and this was
confirmed with fluorescence dual labelling. NPR-A expression was not detected in
the endothelium. Like ANP, DNP fully reversed the constrictor response to ET-1 in
endothelium intact or denuded mammary artery, with comparable nanomolar
potencies. CONCLUSIONS AND IMPLICATIONS: This is the first characterization of
NPR-A in human mammary artery using [(125)I]-DNP and we provide evidence for the
presence of receptor protein on vascular smooth muscle cells, but not endothelial
cells. This implies that the observed vasodilatation is predominantly mediated
via direct activation of smooth muscle NPR-A.
PMID- 17043671
TI - Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and
VR(1) receptors.
AB - BACKGROUND AND PURPOSE: Hyperdynamic circulation and mesenteric hyperaemia are
found in cirrhosis. To delineate the role of endocannabinoids in these changes,
we examined the cardiovascular effects of anandamide, AM251 (CB(1) antagonist),
AM630 (CB(2) antagonist) and capsazepine (VR1 antagonist), in a rat model of
cirrhosis. EXPERIMENTAL APPROACH: Cirrhosis was induced by bile duct ligation.
Controls underwent sham operation. Four weeks later, diameters of mesenteric
arteriole and venule (intravital microscopy), arterial pressure, cardiac output,
systemic vascular resistance and superior mesenteric artery (SMA) flow were
measured after anandamide, AM251 (with or without anandamide), AM630 and
capsazepine administration. CB(1), CB(2) and VR1 receptor expression in SMA was
assessed by western blot and RT-PCR. KEY RESULTS: Anandamide increased mesenteric
vessel diameter and flow, and cardiac output in cirrhotic rats, but did not
affect controls. Anandamide induced a triphasic arterial pressure response in
controls, but this pattern differed markedly in cirrhotic rats. Pre
administration of AM251 blocked the effects of anandamide. AM251 (without
anandamide) increased arterial pressure and systemic vascular resistance,
constricted mesenteric arterioles, decreased SMA flow and changed cardiac output
in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac
output and mesenteric arteriolar diameter and flow, and increased systemic
vascular resistance in cirrhotic rats, but lacked effect in controls. Expression
of CB(1) and VR1 receptor proteins were increased in cirrhotic rats. AM630 did
not affect any cardiovascular parameter in either group. CONCLUSIONS AND
IMPLICATIONS: These data suggest that endocannabinoids contribute to hyperdynamic
circulation and mesenteric hyperaemia in cirrhosis, via CB(1)- and VR1-mediated
mechanisms.
PMID- 17043673
TI - Diazoxide acts more as a PKC-epsilon activator, and indirectly activates the
mitochondrial K(ATP) channel conferring cardioprotection against hypoxic injury.
AB - BACKGROUND AND PURPOSE: Diazoxide, a well-known opener of the mitochondrial ATP
sensitive potassium (mitoK(ATP)) channel, has been demonstrated to exert
cardioprotective effect against ischemic injury through the mitoK(ATP) channel
and protein kinase C (PKC). We aimed to clarify the role of PKC isoforms and the
relationship between the PKC isoforms and the mitoK(ATP) channel in diazoxide
induced cardioprotection. EXPERIMENTAL APPROACH: In H9c2 cells and neonatal rat
cardiomyocytes, PKC-epsilon activation was examined by Western blotting and
kinase assay. Flavoprotein fluorescence, mitochondrial Ca(2+) and mitochondrial
membrane potential were measured by confocal microscopy. Cell death was
determined by TUNEL assay. KEY RESULTS: Diazoxide (100 microM) induced
translocation of PKC-epsilon from the cytosolic to the mitochondrial fraction.
Specific blockade of PKC-epsilon by either epsilonV1-2 or dominant negative
mutant PKC-epsilon (PKC-epsilon KR) abolished the anti-apoptotic effect of
diazoxide. Diazoxide-induced flavoprotein oxidation was inhibited by either
epsilonV1-2 or PKC-epsilon KR transfection. Treatment with 5-hydroxydecanoate (5
HD) did not affect translocation and activation of PKC-epsilon induced by
diazoxide. Transfection with wild type PKC-epsilon mimicked the flavoprotein
oxidizing effect of diazoxide, and this effect was completely blocked by
epsilonV1-2 or 5-HD. Diazoxide prevented the increase in mitochondrial Ca(2+),
mitochondrial depolarization and cytochrome c release induced by hypoxia and all
these effects of diazoxide were blocked by epsilonV1-2 or 5-HD. CONCLUSIONS AND
IMPLICATIONS: Diazoxide induced isoform-specific translocation of PKC-epsilon as
an upstream signaling molecule for the mitoK(ATP) channel, rendering
cardiomyocytes resistant to hypoxic injury through inhibition of the
mitochondrial death pathway.
PMID- 17043674
TI - Toxicity of a trivalent organic arsenic compound, dimethylarsinous glutathione in
a rat liver cell line (TRL 1215).
AB - BACKGROUND AND PURPOSE: Although inorganic arsenite (As(III)) is toxic in humans,
it has recently emerged as an effective chemotherapeutic agent for acute
promyelocytic leukemia (APL). In humans and most animals, As(III) is
enzymatically methylated in the liver to weakly toxic dimethylarsinic acid
(DMAs(V)) that is a major pentavalent methylarsenic metabolite. Recent reports
have indicated that trivalent methylarsenicals are produced through methylation
of As(III) and participate in arsenic poisoning. Trivalent methylarsenicals may
be generated as arsenical-glutathione conjugates, such as dimethylarsinous
glutathione (DMAs(III)G), during the methylation process. However, less
information is available on the cytotoxicity of DMAs(III)G. EXPERIMENTAL
APPROACH: We synthesized and purified DMAs(III)G using high performance TLC
(HPTLC) methods and measured its cytotoxicity in rat liver cell line (TRL 1215
cells). KEY RESULTS: DMAs(III)G was highly cytotoxic in TRL 1215 cells with a
LC(50) of 160 nM. We also found that DMAs(III)G molecule itself was not
transported efficiently into the cells and was not cytotoxic; however it readily
became strongly cytotoxic by dissociating into trivalent dimethylarsenicals and
glutathione (GSH). The addition of GSH in micromolar physiological concentrations
prevented the breakdown of DMAs(III)G, and the DMAs(III)G-induced cytotoxicity.
Physiological concentrations of normal human serum (HS), human serum albumin
(HSA), and human red blood cells (HRBC) also reduced both the cytotoxicity and
cellular arsenic uptake induced by exposure to DMAs(III)G. CONCLUSIONS AND
IMPLICATIONS: These findings suggest that the significant cytotoxicity induced by
DMAs(III)G may not be seen in healthy humans, even if DMAs(III)G is formed in the
body from As(III).
PMID- 17043676
TI - Violent behavior associated with hypocholesterolemia due to a novel APOB gene
mutation.
AB - A 26-year-old male, the index patient, presented with persecutory delusions and
suicidal behavior. He had 10 paternal male relatives in two prior generations.
Five of them died by violent suicide and one, of the five, also committed a
double homicide. The index patient was found to be hypocholesterolemic due to
being heterozygous for a novel mutation of apolipoprotein B (apoB-29.4). His
mother and paternal grandmother were normocholesterolemic, whereas a surviving
paternal uncle was hypocholesterolemic and heterozygous for the apoB-29.4
mutation. This indicated that the index patient's father and paternal
grandfather, both of which died by violent suicide, were obligate heterozygotes
for the apoB-29.4 mutation and that the index patient inherited the mutation from
his paternal grandfather. The odds ratio for the association between
hypocholesterolemia and violent behavior in this family, where cholesterol status
was known, was 16.9 (95% confidence interval 1.1-239.3). Therefore, our results
support an inheritable relationship between violent behavior and
hypocholesterolemia.
PMID- 17043677
TI - Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of
risk genes and a potential synaptic basis for schizophrenia.
AB - Disrupted in Schizophrenia 1 (DISC1) is a schizophrenia risk gene associated with
cognitive deficits in both schizophrenics and the normal ageing population. In
this study, we have generated a network of protein-protein interactions (PPIs)
around DISC1. This has been achieved by utilising iterative yeast-two hybrid
(Y2H) screens, combined with detailed pathway and functional analysis. This so
called 'DISC1 interactome' contains many novel PPIs and provides a molecular
framework to explore the function of DISC1. The network implicates DISC1 in
processes of cytoskeletal stability and organisation, intracellular transport and
cell-cycle/division. In particular, DISC1 looks to have a PPI profile consistent
with that of an essential synaptic protein, which fits well with the underlying
molecular pathology observed at the synaptic level and the cognitive deficits
seen behaviourally in schizophrenics. Utilising a similar approach with dysbindin
(DTNBP1), a second schizophrenia risk gene, we show that dysbindin and DISC1
share common PPIs suggesting they may affect common biological processes and that
the function of schizophrenia risk genes may converge.
PMID- 17043678
TI - Reduced semen quality in chronic prostatitis patients that induce the release of
apoptotic protein Omi/HtrA2 from spermatozoa.
AB - The relationship between chronic prostatitis and fertility has been disputed for
many years. Several groups have shown infection and autoimmune response against
prostate antigens could have a deleterious effect on semen quality and fertility.
This study was conducted to test the hypothesis that Omi/HtrA2-induced apoptosis
in chronic prostatitis could be a mechanism underlying the observed clinical
benefit. The Omi/HtrA2 serine protease is a nuclear-encoded mitochondrial
protein, which can be released from mitochondria into the cytosol after apoptosis
stimuli, inducing apoptosis in caspase-dependent and independent manners. Forty
one patients diagnosed as suffering from chronic prostatitis were included.
Healthy normal individuals were included as controls. Human spermatozoa in the
semen were purified by Percoll-gradient technique to separate the seminal plasma
and other round cells. Measurements for sperm concentration, motility,
morphology, proinflammatory cytokines, Omi/HtrA2 mRNA and protein levels in
spermatozoa of chronic protatitis patients, were performed accordingly.
Significantly increased levels of proinflammatory cytokines were detected in
seminal plasma from these prostatitis patients. Omi/HtrA2 mRNA and protein levels
were significantly higher in prostatitis men than in normal men. This study shows
that chronic prostatitis patients present important alterations in their semen
quality parameters, Omi/HtrA2 mRNA and protein levels of spermatozoa. We
speculate that the inflammatory process involved may affect male fertility by
release of proapoptotic protein Omi/HtrA2.
PMID- 17043680
TI - The treatment of spasticity with Delta9-tetrahydrocannabinol in persons with
spinal cord injury.
AB - STUDY DESIGN: Open label study to determine drug dose for a randomized double
blind placebo-controlled parallel study. OBJECTIVES: To assess the efficacy and
side effects of oral Delta(9)-tetrahydrocannabinol (THC) and rectal THC
hemisuccinate (THC-HS) in SCI patients. SETTING: REHAB Basel, Switzerland.
METHOD: Twenty-five patients with SCI were included in this three-phase study
with individual dose adjustment, each consisting of 6 weeks. Twenty-two
participants received oral THC open label starting with a single dose of 10 mg
(Phase 1, completed by 15 patients). Eight subjects received rectal THC-HS (Phase
2, completed by seven patients). In Phase 3, six patients were treated with oral
THC and seven with placebo. Major outcome parameters were the spasticity sum
score (SSS) using the Modified Ashworth Scale (MAS) and self-ratings of
spasticity. RESULTS: Mean daily doses were 31 mg with THC and 43 mg with THC-HS.
Mean SSS for THC decreased significantly from 16.72 (+/-7.60) at baseline to 8.92
(+/-7.14) on day 43. Similar improvement was seen with THC-HS. We observed a
significant improvement of SSS with active drug (P=0.001) in the seven subjects
who received oral THC in Phase 1 and placebo in Phase 3. Major reasons for drop
out were increase of pain and psychological side effects. CONCLUSION: THC is an
effective and safe drug in the treatment of spasticity. At least 15-20 mg per day
were needed to achieve a therapeutic effect.
PMID- 17043681
TI - Spinal-injured neuropathic bladder antisepsis (SINBA) trial.
AB - OBJECTIVE: To determine whether Methenamine Hippurate (MH) or cranberry tablets
prevent urinary tract infections (UTI) in people with neuropathic bladder
following spinal cord injury (SCI). STUDY DESIGN: Double-blind factorial-design
randomized controlled trial (RCT) with 2 year recruitment period from November
2000 and 6 month follow-up. SETTING: In total, 543 eligible predominantly
community dwelling patients were invited to participate in the study, of whom 305
(56%) agreed. METHODS: Eligible participants were people with SCI with neurogenic
bladder and stable bladder management. All regimens were indistinguishable in
appearance and taste. The dose of MH used was 1 g twice-daily. The dose of
cranberry used was 800 mg twice-daily. The main outcome measure was the time to
occurrence of a symptomatic UTI. RESULTS: Multivariate analysis revealed that
patients randomized to MH did not have a significantly longer UTI-free period
compared to placebo (HR 0.96, 95% CI: 0.68-1.35, P=0.75). Patients randomized to
cranberry likewise did not have significantly longer UTI-free period compared to
placebo (HR 0.93, 95% CI: 0.67-1.31, P=0.70). CONCLUSION: There is no benefit in
the prevention of UTI from the addition of MH or cranberry tablets to the usual
regimen of patients with neuropathic bladder following SCI.
PMID- 17043683
TI - Is thymidylate synthase a reliable predictor for response and survival during
hepatic arterial infusion for hepatic metastases from colorectal cancer?
PMID- 17043684
TI - A third-generation bisphosphonate, minodronic acid (YM529), successfully
prevented the growth of bladder cancer in vitro and in vivo.
AB - Minodronic acid (YM529) is a third-generation bisphosphonate (BP) that has been
shown to directly and indirectly prevent proliferation, induce apoptosis, and
inhibit metastasis of various types of cancer cells. In this study, we have
investigated the therapeutic efficacy of YM529 against bladder cancer, both in
vitro and in vivo. YM529 inhibited geranylgeranylation as well as farnesylation
and reduced the growth of all seven bladder cancer cell lines in a dose- and time
dependent manner in vitro. YM529 demonstrated a good synergistic or additive
antiproliferative effect when administered in combination with cisplatin or
paclitaxel. Immunohistochemical study revealed YM529 inhibited the prenylation of
Rap1A in vivo. YM529 administered systemically did not markedly inhibit the
growth of visceral metastases but it showed a significant anticancer effect on
bone metastases monitored by an in vivo imaging system. Moreover, intravesical
YM529 demonstrated significant growth inhibition in a bladder cancer orthotopic
model. No adverse effects were associated with the systemic as well as the
intravesical treatment regimens. In conclusion, our study suggests that YM529 may
be a potent anticancer agent for bladder cancer. The efficacy and safety of this
BP as an agent for combination chemotherapies against bladder cancer should be
verified by early-phase clinical trials.
PMID- 17043685
TI - Mastectomy rates are decreasing in the era of service screening: a population
based study in Italy (1997-2001).
AB - We enrolled all 2162 in situ and 21 148 invasive cases of breast cancer in 17
areas of Italy, diagnosed in 1997-2001. Rates of early cancer increased by 13.7%
in the screening age group (50-69 years), and breast conserving surgery by 24.6%.
Advanced cancer rates decreased by 19.4%, and mastectomy rates by 24.2%. Service
screening did not increase mastectomy rates in the study population.
PMID- 17043686
TI - Lung cancer risk among German male uranium miners: a cohort study, 1946-1998.
AB - From 1946 to 1990 extensive uranium mining was conducted in the southern parts of
the former German Democratic Republic. The overall workforce included several
100,000 individuals. A cohort of 59,001 former male employees of the Wismut
Company was established, forming a large retrospective uranium miners' cohort for
the time period 1946-1998. Mean duration of follow-up was 30.5 years with a total
of 1 801,630 person-years. Loss to follow-up was low at 5.3%. Of the workers,
16,598 (28.1%) died during the study period. Based on 2388 lung cancer deaths,
the radon-related lung cancer risk is evaluated. The excess relative risk (ERR)
per working level month (WLM) was estimated as 0.21% (95% CI: 0.18-0.24). It was
dependent on time since exposure and on attained age. The highest ERR/WLM was
observed 15-24 years after exposure and in the youngest age group (<55 years of
age). While a strong inverse exposure-rate effect was detected for high
exposures, no significant association was detected at exposures below 100 WLM.
Excess relative risk /WLM was not modified by duration of exposure. The results
would indicate the need to re-estimate the effects of risk modifying factors in
current risk models as duration of exposure did not modify the ERR/WLM and there
was only a modest decline of ERR/WLM with increasing time since exposure.
PMID- 17043688
TI - "I Can't Believe We Don't Know That!".
PMID- 17043689
TI - Low-load eversion force sense, self-reported ankle instability, and frequency of
giving way.
AB - CONTEXT: Functional ankle instability has been attributed to proprioceptive loss.
However, in previous studies of proprioception,authors have not investigated the
ability to sense force at the ankle. Additionally, previous investigators have
viewed functional ankle instability as either a present or absent
condition,rather than a continuum. OBJECTIVE: To determine the relationship of
ankle giving-way frequency and perceived ankle instability to ankle eversion
force sense. DESIGN: Cohort design. SETTING: Sports medicine research laboratory.
PATIENTS OR OTHER PARTICIPANTS: Twenty individuals (5 men,15 women) with a
history of unilateral ankle instability. INTERVENTION(S): We tested subjects with
2 loads: 10% and 30% of maximal voluntary isometric contraction. MAIN OUTCOME
MEASURE(S): We measured eversion force sense by calculating absolute, constant,
and variable errors from a 3-trial force-matching procedure. Furthermore,
subjects reported their frequency of giving way in units of times per day,week,
or month, and these data were extrapolated to estimate annual giving-way
frequency. Finally, subjects answers to 6 questions about ankle stability during
typical daily or sports activities were summed to create a perceived ankle
instability index. RESULTS: Significant relationships were found for only the 10%
maximal voluntary isometric contraction. For absolute error,a positive
relationship existed between the number of self reported episodes of giving way
and eversion force sense for both ipsilateral (r .58) and contralateral (r .49)
testing of the injured ankle. Constant error was correlated with giving way(r =
.56) for ipsilateral testing of the injured ankle. The ankle instability index
was also positively correlated with eversion force sense absolute error (r .51)
for ipsilateral testing only. CONCLUSIONS: Our results suggest that subjects with
ankle instability had difficulty replicating eversion forces. Specifically,larger
errors were related to both self-reported giving-way episodes and perceived ankle
instability.
PMID- 17043687
TI - Insulin receptor substrates mediate distinct biological responses to insulin-like
growth factor receptor activation in breast cancer cells.
AB - Activation of the type I insulin-like growth factor receptor (IGF-IR) regulates
several aspects of the malignant phenotype, including cancer cell proliferation
and metastasis. Phosphorylation of adaptor proteins downstream of IGF-IR may
couple IGF action to specific cancer phenotypes. In this study, we sought to
determine if insulin receptor substrate-1 and -2 (IRS-1 and -2) mediate distinct
biological effects in breast cancer cells. Insulin receptor substrate-1 and IRS-2
were expressed in T47D-YA breast cancer cells, which lack IRS-1 and -2
expression, yet retain functional IGF-IR. In the absence of IRS-1 and -2
expression, IGF-IR activation was unable to stimulate proliferation or motility
in T47D-YA cells. Expression of IRS-1 resulted in IGF-I-stimulated proliferation,
but did not affect motility. In contrast, expression of IRS-2 enhanced IGF-I
stimulated motility, but did not stimulate proliferation. The alphaIR-3, an
inhibitor of the IGF-IR, was unable to affect these IGF-stimulated phenotypes
unless IRS-1 or -2 was expressed. Thus, IGF-IR alone is unable to regulate
important breast cancer cell phenotypes. In these cells, IRS proteins are
required for and mediate distinct aspects of IGF-IR-stimulated behaviour. As
multiple agents targeting the IGF-IR are currently in early clinical trials, IRS
expression should be considered as a potential biomarker for IGF-IR
responsiveness.
PMID- 17043690
TI - Prophylactic ankle braces and knee varus-valgus and internal-external rotation
torque.
AB - CONTEXT: Although prophylactic ankle bracing has been shown to be effective in
reducing the incidence of ankle sprains,how these ankle braces might affect the
other joints of the lower extremity is not clearly understood. OBJECTIVE: To
determine the effects of a prophylactic ankle brace on knee joint varus-valgus
and internal-external rotation torque during a drop landing onto a slanted
surface. DESIGN: A repeated-measures design. SETTING: Biomechanics research
laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-four physically active college
students. INTERVENTION(S): Participants were tested in a brace and no brace
condition. MAIN OUTCOME MEASURE(S): We measured 3 dependent variables:(1) peak
ankle inversion-eversion torque, (2) peak knee varus-valgus torque, and (3) peak
knee internal-external rotation torque. A force plate was used to collect ground
reaction force data, and 6 motion analysis cameras collected kinematic data
during the unilateral drop landing. An adjustable bar was hung from the ceiling,
and a slant board was positioned over the center of the force plate, so that the
ankle of the participant's dominant leg would invert upon landing. Peak torque
was measure din both the brace and no-brace conditions. The average of the peak
values in 3 trials for both conditions was used for the statistical analysis.
RESULTS: Ankle eversion torque was significantly greater in the brace condition
(F1,23 19.75, P < .01). Knee external rotation torque was significantly greater
in the brace condition(F1,23 4.33, P <.05). Valgus knee torque was smaller in the
brace condition, but the difference was not statistically significant(F1,23 3.45,
P .08). CONCLUSIONS: This study provides an important first step in understanding
the effects of prophylactic ankle bracing on other joints of the lower extremity.
We found that prophylactic ankle bracing did have an effect on knee torque when
the subject was landing on a slanted surface. Specifically, knee external
rotation torque increased when the ankle was braced.
PMID- 17043691
TI - Dynamic postural stability in subjects with braced, functionally unstable ankles.
AB - CONTEXT: Research concerning prophylactic ankle stabilizers (PASs) has focused on
healthy subjects, and the results cannot be generalized to the functional ankle
instability (FAI) population, a population that has an increased risk of reinjury
and is likely to wear PASs. OBJECTIVE: To determine whether PASs improve dynamic
postural stability in FAI subjects as compared with a control (no-brace)
condition. DESIGN: A crossover design was used to determine the effects of PASs
on dynamic postural stability and vertical ground reaction forces. SETTING:
Biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-eight subjects
with unilateral FAI, 13 men (age = 21.5 +/- 1.2 years, height = 181.5 +/- 10.5
cm, mass = 77.6 +/- 17.2 kg) and 15 women (age = 20.5 +/- 1.1 years, height =
169.4 +/- 8.2 cm, mass = 67.9 +/- 8.8 kg). INTERVENTION(S): A jump protocol
required subjects to perform a 2-legged jump to a height equivalent to 50% of
their maximum vertical leap and land on a single leg. MAIN OUTCOME MEASURE(S):
The dynamic postural stability index, the directional components (medial-lateral,
anterior-posterior, and vertical), and vertical ground reaction force after a
jump landing. RESULTS: Compared with the control condition, only the vertical
component score was reduced (improved) with the application of a soft or
semirigid PAS (P < .01). CONCLUSIONS: Soft and semirigid PASs did not improve
dynamic postural stability as measured by the Dynamic Postural Stability Index.
However, PASs may help with the attenuation of vertical forces.
PMID- 17043692
TI - The independent and interactive effects of navicular drop and quadriceps angle on
neuromuscular responses to a weight-bearing perturbation.
AB - CONTEXT: Little is known about the effects of static alignment on neuromuscular
control of the knee during dynamic motion. OBJECTIVE: To evaluate the isolated
and combined effects of quadriceps angle (QA) and navicular drop (ND) on
neuromuscular responses to a weight-bearing perturbation. DESIGN: Mixed-model,
repeated-measures design. SETTING: Sports medicine and athletic training research
laboratory. PATIENTS OR OTHER PARTICIPANTS: Seventy-nine National Collegiate
Athletic Association Division I collegiate female athletes, classified with below
average ND and QA (LND-LQA); below-average ND and above-average QA (LND-HQA);
above-average ND and below-average QA (HND-LQA); or above-average ND and QA (HND
HQA). INTERVENTION(S): A lower extremity perturbation device produced a forward
and either internal or external rotation of the trunk and femur on the weight
bearing tibia to evoke a reflex response. MAIN OUTCOME MEASURE(S): Neuromuscular
responses were examined in the quadriceps, hamstrings, and gastrocnemius muscles:
preperturbation amplitude 50 milliseconds before the perturbation, reflex time,
and postperturbation amplitude 150 milliseconds immediately postperturbation.
RESULTS: Navicular drop had the greatest effect on preperturbation amplitude of
the lateral hamstrings and postperturbation amplitude of all muscles, with
greater activation amplitude noted in subjects in the HND classifications.
Quadriceps angle primarily affected reflex time of the quadriceps; in subjects
with LQA, reflex time was faster for internal rotation than external rotation
perturbations. The interaction between ND and QA had the greatest effect on
reflex time of the lateral hamstrings. For internal rotation perturbations,
subjects in the LND classifications had faster reflex times in the lateral
hamstrings if they had HQA values rather than LQA values. With external rotation
perturbations, HND-LQA subjects had slower reflex times than those in all other
alignment classifications. CONCLUSIONS: Navicular drop and QA have both
independent and interactive effects on neuromuscular responses to a weight
bearing, rotational perturbation. These interactive effects highlight the
importance of considering the entire lower extremity posture rather than a single
alignment characteristic, given the potential for one alignment factor to
compensate for or interact with another.
PMID- 17043693
TI - Quadriceps inhibition after repetitive lumbar extension exercise in persons with
a history of low back pain.
AB - CONTEXT: A neuromuscular relationship exists between the lumbar extensor and
quadriceps muscles during fatiguing exercise. However, this relationship may be
different for persons with low back pain (LBP). OBJECTIVE: To compare quadriceps
inhibition after isometric, fatiguing lumbar extension exercise between persons
with a history of LBP and control subjects. DESIGN: A 2 x 3 factorial, repeated
measures, time-series design with independent variables of group (persons with a
history of LBP, controls) and time (baseline, postexercise set 1, postexercise
set 2). SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS:
Twenty-five subjects with a history of LBP were matched by sex, height, and mass
to 25 healthy control subjects. INTERVENTION(S): Electromyography median
frequency indexed lumbar paraspinal muscular fatigue while subjects performed 2
sets of isometric lumbar extension exercise. Subjects exercised until a 15%
downward shift in median frequency for the first set and a 25% shift for the
second set were demonstrated. MAIN OUTCOME MEASURE(S): Knee extension force was
measured while subjects performed an isometric maximal quadriceps contraction.
During this maximal effort, a percutaneous electric stimulus was applied to the
quadriceps, causing a transient, supramaximal increase in force output. We used
the ratio between the 2 forces to estimate quadriceps inhibition. Quadriceps
electromyographic activity was recorded during the maximal contractions to
compare median frequencies over time. RESULTS: Both groups exhibited
significantly increased quadriceps inhibition after the first (12.6% +/- 10.0%, P
< .001) and second (15.2% +/- 9.7%, P < .001) exercise sets compared with
baseline (9.6% +/- 9.3%). However, quadriceps inhibition was not different
between groups. CONCLUSIONS: Persons with a history of LBP do not appear to be
any more or less vulnerable to quadriceps inhibition after fatiguing lumbar
extension exercise.
PMID- 17043694
TI - Acute muscle stretching and shoulder position sense.
AB - CONTEXT: Stretching is common among athletes as a potential method for injury
prevention. Stretching-induced changes in the muscle spindle properties are a
suggested mechanism, which may imply reduced proprioception after stretching;
however, little is known of this association. OBJECTIVE: To evaluate whether
acute stretching of the shoulder muscles affects position sense. DESIGN: A
crossover design with subjects randomized to 3 groups. SETTING: A university
human research laboratory. PATIENTS OR OTHER PARTICIPANTS: Nine male (age = 24 +/
3 years) and 9 female (age = 21 +/- 2 years) healthy volunteers.
INTERVENTION(S): Stretching of shoulder (1) agonists or (2) antagonists or (3)
nonstretching control. MAIN OUTCOME MEASURE(S): We determined position sense
acuity of the right shoulder before and after the interventions by having
subjects attempt to reproduce arm positions of 15 degrees and 30 degrees
(shoulder adduction) while starting at 45 degrees to the sagittal plane. The
outcome variables were response variability (variable error) and overall accuracy
(absolute error). RESULTS: The relative change in variable error (ie, variable
error after/variable error before) was not significantly different between the
interventions ( P = .38). Similarly, no change in absolute error was found ( P =
.76). Furthermore, no differences were noted regarding test sequence or the
interaction of intervention x sequence for either variable error ( P = .73 and
.53, respectively) or absolute error ( P = .71 and .67, respectively).
CONCLUSIONS: We found no effect on shoulder position sense after an acute bout of
stretching of either agonist or antagonist shoulder muscles.
PMID- 17043695
TI - A functional fatiguing protocol and deceleration time of the shoulder from an
internal rotation perturbation.
AB - CONTEXT: Muscular fatigue impedes sensorimotor function and may increase the risk
of shoulder injury during activity. The effects of fatigue on the sensorimotor
system of the shoulder have been studied with various results. Deceleration times
have been used to study neuromuscular control of the shoulder; however, no
studies involving the effects of fatigue on deceleration times have been
reported. OBJECTIVE: To compare shoulder deceleration times after a shoulder
internal rotation perturbation before and after a repetitive throwing exercise
protocol. DESIGN: A 2 x 2 repeated-measures design. SETTING: Exercise and sport
injury laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty healthy, recreationally
active men (age = 24.76 +/- 4.03 years, height = 178.41 +/- 8.36 cm, mass = 80.16
+/- 15.20 kg) volunteered to participate in the study. To ensure familiarity with
the overhead motion, all subjects chosen had previously participated in an
overhead throwing sport. INTERVENTION(S): The independent variables were time
(preintervention and postintervention) and session (experimental and control).
The intervention consisted of continuous overhead throwing. The subjects were
considered fatigued when a 10% decrease in velocity was noted on 3 consecutive
pitches. MAIN OUTCOME MEASURE(S): Time necessary to decelerate from an internal
rotation perturbation. RESULTS: Deceleration time was significantly increased by
the fatiguing intervention ( P = .001). CONCLUSIONS: The decreased ability to
decelerate may be an adaptive response by the subjects to dissipate a lower
percentage of force per second.
PMID- 17043696
TI - Flexible foil exercise and shoulder internal and external rotation strength.
AB - CONTEXT: The efficacy of exercise using a flexible foil to increase strength in
the shoulder rotator muscles is unknown. OBJECTIVE: To compare the effects of
exercises using a flexible foil (Bodyblade) with exercises using elastic bands on
shoulder internal and external rotator muscle strength. DESIGN: We used a
randomized, controlled pretest-posttest design. SETTING: Laboratory. PATIENTS OR
OTHER PARTICIPANTS: Forty young adults with no previous shoulder injury.
INTERVENTION(S): Experimental subjects participated in an 8-week program of
internal and external rotation exercises consisting of 3 sessions per week. MAIN
OUTCOME MEASURE(S): Strength was tested by internal and external rotation
isometric and isokinetic strength tests at 60 degrees .s (-1) and 120 degrees .s
(-1). RESULTS: The group exercising with elastic bands had a greater pretest
posttest increase in maximal internal rotation isometric torque at 10 degrees of
internal rotation and greater maximal external rotation isometric torque at 65
degrees of external rotation than the control group. The group using a flexible
foil did not show an increase in strength significantly different from either the
control or elastic band groups. We found no other statistically significant
differences. CONCLUSIONS: Our results do not support the use of a flexible foil
for strength gains in shoulder internal and external rotation in the asymptomatic
young adult population.
PMID- 17043697
TI - Improving strength and postural control in young skiers: whole-body vibration
versus equivalent resistance training.
AB - CONTEXT: Several groups have undertaken studies to evaluate the physiologic
effects of whole-body vibration (WBV). However, the value of WBV in a training
program remains unknown. OBJECTIVE: To investigate whether a WBV program results
in a better strength and postural control performance than an equivalent exercise
program performed without vibration. DESIGN: Randomized, controlled trial.
SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty-three Belgian
competitive skiers (ages = 9-15 years). INTERVENTION(S): Subjects were assigned
to either the WBV group or the equivalent resistance (ER) group for 6 weeks of
training at 3 times per week. MAIN OUTCOME MEASURE(S): Isokinetic plantar and
dorsiflexion peak torque, isokinetic knee flexion and extension peak torque,
explosive strength (high box test), and postural control were assessed before and
after the training period. RESULTS: Both training programs significantly improved
isokinetic ankle and knee muscle strength and explosive strength. Moreover, the
increases in explosive strength and in plantar-flexor strength at low speed were
significantly higher in the WBV group than in the ER group after 6 weeks.
However, neither WBV training nor ER training seemed to have an effect on
postural control. CONCLUSIONS: A strength training program that includes WBV
appears to have additive effects in young skiers compared with an equivalent
program that does not include WBV. Therefore, our findings support the hypothesis
that WBV training may be a beneficial supplementary training technique in
strength programs for young athletes.
PMID- 17043698
TI - Fatigue, vertical leg stiffness, and stiffness control strategies in males and
females.
AB - CONTEXT: Fatigue appears to influence musculoskeletal injury rates during
athletic activities, but whether males and females respond differently to fatigue
is unknown. OBJECTIVE: To determine the influence of fatigue on vertical leg
stiffness (K (VERT)) and muscle activation and joint movement strategies and
whether healthy males and females respond similarly to fatigue. DESIGN: Repeated
measures design with all data collected during a single laboratory session.
SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Physically active males (n =
11) and females (n = 10). INTERVENTION(S): Subjects performed hopping protocols
at 2 frequencies before and after fatigue, which was induced by repeated
squatting at submaximal loads. MAIN OUTCOME MEASURE(S): We measured K (VERT) with
a forceplate and peak muscle activity of the quadriceps, hamstrings,
gastrocnemius, soleus, and anterior tibialis muscles with surface
electromyography. Sagittal-plane kinematics at the knee and ankle were recorded
with an electrogoniometer. RESULTS: After fatigue, K (VERT) was unchanged for all
subjects. However, both males and females demonstrated reduced peak hamstrings (
P = .002) and anterior tibialis ( P = .001) activation, coupled with increased
gastrocnemius ( P = .005) and soleus ( P = .001) peak activity, as well as
increased quadriceps-hamstrings ( P = .005) and gastrocnemius/soleus-anterior
tibialis coactivation ratios ( P = .03) after fatigue. Overall, females
demonstrated greater quadriceps-hamstrings coactivation ratios than males,
regardless of the fatigue condition ( P = .026). Only females showed increased
knee flexion at initial contact after fatigue during hopping ( P = .03).
CONCLUSIONS: Although K (VERT) was unaffected, the peak muscle activation and
joint movement strategies used to modulate K (VERT) were affected after fatigue.
Once fatigued, both males and females used an ankle-dominant strategy, with
greater reliance on the ankle musculature and less on the knee musculature. Also,
once fatigued, all subjects used an antagonist inhibition strategy by minimizing
antagonist coactivation. Overall, females used a more quadriceps-dominant
strategy than males, showing greater quadriceps activity and a larger quadriceps
hamstrings coactivation ratio. Changes in muscle activation and coactivation
ratios because of fatigue and sex are suggested to alter knee joint stability and
increase anterior cruciate ligament injury risk.
PMID- 17043699
TI - Recovery of postural control after cerebral concussion: new insights using
approximate entropy.
AB - CONTEXT: The return-to-play decision after sport-related cerebral concussion
depends in part on knowing when an athlete has fully recovered postural control
after injury. OBJECTIVE: To describe the postconcussion recovery of postural
control using approximate entropy (ApEn), a regularity statistic from nonlinear
dynamics. DESIGN: Retrospective case series analysis. SETTING: Sports medicine
research laboratory. PATIENTS OR OTHER PARTICIPANTS: Collegiate athletes from
whom center-of-pressure and symptom data were collected at preseason, less than
48 hours after injury, and 48 to 96 hours after injury. MAIN OUTCOME MEASURE(S):
Approximate entropy values reflecting the amount of randomness contained in
center-of-pressure oscillations were calculated for anterior-posterior (AP) and
medial-lateral (ML) time series. Equilibrium scores reflecting the amplitude of
center-of-pressure AP oscillations were used to indicate postural stability. The
number and severity of symptoms were described. RESULTS: Compared with the
healthy preseason state, ApEn values for the AP and ML time series generally
declined immediately after injury in both steady and unsteady injured athletes.
At 48 to 96 hours after injury, ApEn values for the ML time series remained
significantly depressed (mean difference compared with preseason = -0.268,
standard error = 0.072), even among athletes whose initial postural instability
had resolved. We found few significant relationships between changes in ApEn
values and changes in symptoms before and after injury. CONCLUSIONS: The effects
of cerebral concussion on postural control appear to persist for longer than 3 to
4 days, even among athletes with no signs of unsteadiness. Our results may
reflect changes in neurophysiologic or mechanical constraints on postural
control. Approximate entropy provides a theoretically distinct, valuable
measurement alternative that may prove useful for reducing uncertainty in the
return-to-play decision.
PMID- 17043700
TI - Surface electromyographic amplitude-to-work ratios during isokinetic and isotonic
muscle actions.
AB - CONTEXT: Isokinetic and isotonic resistance training exercises are commonly used
to increase strength during musculoskeletal rehabilitation programs. Our study
was designed to examine the efficacy of isokinetic and isotonic muscle actions
using surface electromyographic (EMG) amplitude-to-work ratios (EMG/WK) and to
extend previous findings to include a range of isokinetic velocities and isotonic
loads. OBJECTIVE: To examine work (WK), surface EMG amplitude, and EMG/WK during
concentric-only maximal isokinetic muscle actions at 60, 120, 180, 240, and 300
degrees /s and isotonic muscle actions at 10%, 20%, 30%, 40%, and 50% of the
maximal voluntary isometric contraction (MVIC) torque during leg extension
exercises. DESIGN: A randomized, counterbalanced, cross-sectional, repeated
measures design. SETTING: A university-based human muscle physiology research
laboratory. PATIENTS OR OTHER PARTICIPANTS: Ten women (mean age = 22.0 +/- 2.6
years) and 10 men (mean age = 20.8 +/- 1.7 years) who were apparently healthy and
recreationally active. INTERVENTION(S): Using the dominant leg, each participant
performed 5 maximal voluntary concentric isokinetic leg extension exercises at
randomly ordered angular velocities of 60, 120, 180, 240, and 300 degrees /s and
5 concentric isotonic leg extension exercises at randomly ordered loads of 10%,
20%, 30%, 40%, and 50% of the isometric MVIC. MAIN OUTCOME MEASURE(S): Work was
recorded by a Biodex System 3 dynamometer, and surface EMG was recorded from the
superficial quadriceps femoris muscles (vastus lateralis, rectus femoris, and
vastus medialis) during the testing and was normalized to the MVIC. The EMG/WK
ratios were calculated as the quotient of EMG amplitude (muVrms) and WK (J)
during the concentric phase of each exercise. RESULTS: Isotonic EMG/WK remained
unchanged ( P > .05) from 10% to 50% MVIC, but isokinetic EMG/WK increased ( P <
.05) from 60 to 300 degrees /s. Isotonic EMG/WK was greater ( P < .05) than
isokinetic EMG/WK for 50% MVIC versus 60 degrees /s, 40% MVIC versus 120 degrees
/s, and 30% MVIC versus 180 degrees /s; however, no differences were noted ( P >
.05) between 20% MVIC versus 240 degrees /s or 10% MVIC versus 300 degrees /s. An
18% decrease in active range of motion was seen for the isotonic muscle actions,
from 10% to 50% MVIC, and a 3% increase in range of motion for the isokinetic
muscle actions from 60 to 300 degrees /s was also observed. Furthermore, the peak
angular velocities for the isotonic muscle actions ranged from 272.9 to 483.0
degrees /s for 50% and 10% MVIC, respectively. CONCLUSIONS: When considering
EMG/WK, peak angular velocity, and range of motion together, our data indicate
that maximal isokinetic muscle actions at 240 degrees /s or controlled-velocity
isotonic muscle actions at 10%, 20%, or 30% MVIC may maximize the amount of
muscle activation per unit of WK done during the early stages of musculoskeletal
rehabilitation. These results may be useful to allied health professionals who
incorporate open-chain resistance training exercises during the early phases of
rehabilitation and researchers who use isotonic or isokinetic modes of resistance
exercise to examine muscle function.
PMID- 17043701
TI - Cortisol concentrations in human skeletal muscle tissue after phonophoresis with
10% hydrocortisone gel.
AB - CONTEXT: The delivery of hydrocortisone through phonophoresis is a widely
prescribed technique for the treatment of various musculoskeletal inflammatory
conditions. However, limited scientific evidence exists to support the efficacy
of phonophoresis in delivering hydrocortisone to skeletal muscle tissue in
humans. OBJECTIVE: To determine hydrocortisone (cortisol) concentrations in human
skeletal muscle tissue after a phonophoresis treatment using 10% hydrocortisone
gel. DESIGN: Randomized design in which 12 subjects were randomly assigned to
either an ultrasound (sham) treatment or a 10% hydrocortisone phonophoresis
treatment. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Twelve healthy
subjects (8 women, 4 men: age = 22.3 +/- 2.64 years, height = 168.28 +/- 8.19 cm,
mass = 69.58 +/- 9.05 kg) with no history of musculoskeletal disease, preexisting
inflammatory conditions, or recent orthopaedic injuries. INTERVENTION(S):
Ultrasound at 1.0 MHz, 1.0 W/cm (2), at a continuous setting for 7 minutes was
applied to a standardized area of the vastus lateralis muscle in both groups. The
contralateral limb served as the control (no treatment) for both the sham and the
phonophoresis groups. MAIN OUTCOME MEASURE(S): Vastus lateralis muscle biopsies
were taken from both legs immediately after treatment, and cortisol
concentrations were analyzed using an enzyme-linked immunosorbent assay. RESULTS:
We observed no significant difference in muscle cortisol concentration between
the contralateral control limb and the treatment limb in either the sham or the
phonophoresis group ( P > .05). No significant difference was noted when the
treatment limbs in the sham and phonophoresis groups were compared ( P > .05).
CONCLUSIONS: Our data suggest that a 10% hydrocortisone-based phonophoresis
treatment did not increase cortisol concentrations in human skeletal muscle
tissue.
PMID- 17043702
TI - Injuries sustained by rugby players presenting to United States emergency
departments, 1978 through 2004.
AB - CONTEXT: Although the United States has nearly 60 000 rugby players, to date no
nationally representative rugby injury studies have been conducted. OBJECTIVE: To
describe rugby players with injuries presenting to a representative sample of US
emergency departments from 1978 through 2004. DESIGN: Retrospective study.
SETTING: US Consumer Products Safety Commission's National Electronic Injury
Surveillance System. PATIENTS OR OTHER PARTICIPANTS: Rugby players presenting to
emergency departments in participating hospitals from October 1, 1978, through
December 31, 2004. MAIN OUTCOME MEASURE(S): We reviewed all rugby players with
injuries captured by the National Electronic Injury Surveillance System and
categorized them by sex, age, injury site, and injury diagnosis. RESULTS: An
estimated 236 539 rugby players presented to US emergency departments from 1978
through 2004. Injured athletes tended to be male (87.2%) and older than 18 years
of age (86.0%). The face (20.5%), shoulder (14.1%), head (11.5%), and ankle
(9.1%) were the most frequently injured sites. Strain/sprain (24.3%), laceration
(22.1%), fracture (18.7%), and contusion/abrasion (16.6%) were the most common
diagnoses. Males presented with more face injuries (injury proportion ratio [IPR]
= 2.05, 95% confidence interval [CI] = 1.54-2.72, P < .001) and more lacerations
(IPR = 4.23, 95% CI = 2.87-6.22, P < .001) and dislocations (IPR = 2.17, 95% CI
1.51-3.13, P < .001). Females presented with more knee injuries (IPR = 1.67, 95%
CI = 1.36-2.06, P < .001) and more contusions/abrasions (IPR = 1.48, 95% CI =
1.14-1.92, P < .001) and strains/sprains (IPR = 1.39, 95% = CI 1.16-1.67, P <
.001). Those 18 years of age or younger presented with more concussions (IPR =
1.62, 95% CI = 1.06-2.50, P < .001), while those over 18 presented with more
lacerations (IPR = 1.83, 95% CI = 1.30-2.57, P < .001). In males, fractures were
more common among those 18 years of age or younger (IPR = 1.47, 95% CI = 1.24
1.75, P < .001). CONCLUSIONS: Rugby injury patterns in the United States differed
by age and sex. Understanding such patterns should assist certified athletic
trainers in developing targeted preventive interventions.
PMID- 17043703
TI - Exertional heat illness and environmental conditions during a single football
season in the southeast.
AB - CONTEXT: Recommendations for heat illness prevention provided by sports medicine
associations do not always account for sex differences, specific age populations,
regional environmental conditions, equipment worn during activity, or the
athlete's size or preexisting level of fitness. OBJECTIVE: To evaluate the rate
of exertional heat illness (EHI) among collegiate football athletes and to
monitor environmental conditions during American football practice for a 3-month
period. DESIGN: Epidemiologic study in which we reviewed the occurrence rates of
EHI and wet bulb globe temperature readings during a 3-month period of American
collegiate football practice sessions. SETTING: Five universities in the
southeastern region of the United States. PATIENTS OR OTHER PARTICIPANTS:
Collegiate football players at the 5 universities. MAIN OUTCOME MEASURE(S): Wet
bulb globe temperatures were recorded from August through October 2003, at the
beginning, middle, and end of each practice session. The EHIs were identified and
recorded, and athlete-exposures (AEs) were calculated. RESULTS: A total of 139
EHIs and 33 196 AEs were reported (EHI rate = 4.19/1000 AEs). The highest
incidence of EHIs was in August (88%, EHI rate = 8.95/1000 AEs) and consisted of
70% heat cramps (6.13/1000 AEs), 23% heat exhaustion (2.06/ 1000 AEs), and 7%
heat syncope (0.58/1000 AEs). No cases of heat stroke or hyponatremia were
identified. The highest risk of EHI occurred during the first 3 weeks of the
study; mean wet bulb globe temperature declined significantly as the study
continued ( P < .001). Temperatures in the final 5 weeks of the study were
significantly cooler than in the first 5 weeks ( P < .05). CONCLUSIONS: Heat
cramps were the most common EHI and occurred most often during the first 3 weeks
of practice. Athletic trainers should take all necessary preventive measures to
reduce the risk of EHI.
PMID- 17043704
TI - Community-acquired methicillin-resistant Staphylococcus aureus: prevalence and
risk factors.
PMID- 17043705
TI - Central cord syndrome in a high school wrestler: a case report.
AB - OBJECTIVE: To alert athletic trainers to the importance of recognizing the signs
and symptoms of central cord syndrome. BACKGROUND: A 15-year-old high school
wrestler was found lying supine on the mat after sustaining a hyperextension
injury to his neck while drilling during practice, complaining of numbness,
tingling, and a burning sensation in all 4 extremities. Touching the extremities
elicited an extreme burning sensation. After in-line stabilization of the
cervical spine was performed, palpation of the spinous processes elicited
tenderness and an increase in pain. Six weeks before the injury, the athlete had
experienced forced lateral flexion of the cervical spine during a match,
resulting in an episode of bilateral numbness and burning in his arms. On
evaluation by the athletic trainer, symptoms were limited to the right hand, and
brachial plexus neurapraxia was diagnosed. DIFFERENTIAL DIAGNOSIS: Central cord
syndrome, brachial plexus injury, cervical spine injury, burning hands syndrome,
Brown-Sequard syndrome, anterior cord syndrome. TREATMENT: Upon assessment, the
athlete's cervical spine was immobilized until emergency medical services arrived
and applied a cervical collar. Radiographs taken at the hospital revealed a
congenital fusion of C6-7. Magnetic resonance imaging and computed tomography
showed evidence of stenosis, a herniated disc at C3-4, and a central cord injury.
He was admitted to the hospital for observation and was placed on a
corticosteroid protocol. At approximately 1 week after the injury, the athlete
underwent a cervical decompression and fusion at C3-4. Subsequently, he underwent
extensive rehabilitation and has had some persistent neck stiffness. The athlete
is no longer allowed to participate in contact sports as a result of the presence
of stenosis at multiple levels. UNIQUENESS: Central cord syndrome is typically
seen in an older population with cervical spondylosis and rarely occurs in young
adolescents. However, this athlete sustained 2 central cord injuries, 1 mild and
1 severe, in less than 6 weeks' time. CONCLUSIONS: The original injury sustained
by the wrestler was thought to be a brachial plexus injury but, in fact, was a
mild central cord injury. Central cord syndrome was not suspected in the original
injury because the athlete's complaint was of unilateral numbness. With the
second injury, the central cord injury was more severe. Proper recognition,
assessment, and handling of this situation were crucial in providing optimal care
to this athlete.
PMID- 17043706
TI - Management of overactive bladder with transdermal oxybutynin.
AB - In clinical trials, transdermal oxybutynin (OXY-TDS) has shown comparable
efficacy and improved tolerability when compared with conventional
pharmacotherapy. Systemic anticholinergic adverse effects are comparable to those
with placebo, most likely owing to avoidance of first-pass hepatic metabolism and
conversion of oxybutynin to N-desethyloxybutynin. OXY-TDS has predictable
pharmacokinetic absorption and elimination parameters, as shown in both in vitro
and in vivo studies. Consistent plasma concentrations of oxybutynin avoid labile
peak and trough concentrations seen with immediate-release formulations,
paralleling extended-release drug delivery. This novel drug delivery system has
unique dermatologic skin application site reactions, including erythema and
pruritus. Skin reactions are usually mild and can be minimized by varying the
site of patch application. Most eczematous dermatologic reactions can be
appropriately treated with a moderately potent topical corticosteroid cream. A
small percentage of patients will discontinue therapy as a result of bothersome
application site skin reactions.
PMID- 17043707
TI - New generation tissue sealants and hemostatic agents: innovative urologic
applications.
AB - Control of blood loss during urologic surgery is paramount to the success of
patient recovery. Hemostatic agents and tissue sealants are used routinely to
prevent excess blood loss and in reconstruction during surgical repair. Some of
the available products include thrombin sealant, fibrin glue, bovine
serum/albumin/glutaraldehyde, and gelatin matrix. Each of these agents differs in
mechanism, cost, and application. Complications can include allergic reactions or
thromboembolism and the risk of contracting bovine spongiform encephalitis or
hepatitis. Many new hemostatic agents are being developed and approved. The
benefits and risks of use of these agents versus conventional treatment need to
be considered on a case-by-case basis by the surgeon.
PMID- 17043708
TI - The importance of pelvic lymph node dissection in men with clinically localized
prostate cancer.
AB - Despite advances in noninvasive staging, pelvic lymph node dissection (PLND)
remains the most accurate means of detecting lymph node metastases in men with
clinically localized prostate cancer. Nomograms exist that can identify patients
at low risk for lymphatic metastases according to preoperative information. In
general, it seems reasonable to omit PLND in men with a biopsy Gleason sum of 6
or less and a prostate-specific antigen level of 10 ng/mL or less. Ultimately,
however, this decision should be made according to physician and patient
preference, considering the low contemporary morbidity associated with PLND. When
PLND is performed, studies suggest that an extended dissection maximizes the
detection rate of nodal involvement. Retrospective data indicate that an extended
dissection might play a therapeutic role in a subset of patients with a limited
lymph node burden. However, this might be an artifact of stage migration, and
prospective studies are needed to evaluate this further.
PMID- 17043709
TI - Best of the 2006 AUA Annual Meeting: Highlights from the 2006 Annual Meeting of
the American Urological Association, May 20-25, 2006, Atlanta, GA.
PMID- 17043710
TI - Spurious hypocalcemia after gadodiamide-enhanced magnetic resonance imaging: a
case report and review of the literature.
AB - Gadolinium-enhanced magnetic resonance imaging is a diagnostic modality widely
used in urologic practice. We report on a 54-year-old woman in whom a critically
low serum calcium level was measured with standard colorimetric assay after
gadodiamide-enhanced magnetic resonance imaging. The same phenomenon was noted in
2 other patients seen in our practice. Repeat serum calcium measurements
performed several hours later were within normal limits. Commercially available
gadolinium-based contrast agents might precipitate critically low serum calcium
values when measured by standard colorimetric assay. Physician awareness of
gadodiamide-induced spurious hypocalcemia might prevent unnecessary therapeutic
interventions.
PMID- 17043711
TI - Disappointing news for urologists managing interstitial cystitis patients.
PMID- 17043712
TI - Probiotic therapy for hyperoxaluria.
PMID- 17043713
TI - TESA or TESE: Which Is Better for Sperm Extraction?
PMID- 17043714
TI - Recurrent pregnancy loss: who is to blame?
PMID- 17043715
TI - Using spin polarised positive muons for studying guest molecule partitioning in
soft matter structures.
AB - Fully polarised positive muons substituted for protons in organic free radicals
can be used as spin labels which reveal information about the structure, dynamics
and environment of these radicals. In applications via the technique of avoided
level-crossing muon spin resonance (ALC-microSR), the positive muon has been used
to study the partitioning of phenyl alcohols in lamellar phase colloidal
dispersions of a cationic dichain surfactant. Here we describe the experimental
technique which permits highly sensitive spectroscopy as previously demonstrated
for surfactant mixtures. We also demonstrate its capability in the study of
partitioning of cosurfactant molecules in surfactant bilayers in order to
elucidate the main factors which contribute to cosurfactant ordering at
interfaces. The technique takes advantage of the positive muon combining with an
electron to a hydrogen-like atom that is called muonium. This atom attaches to a
phenyl group, forming a cyclohexadienyl-type radical that contains the muon as a
polarised spin label, providing an excellent probe even for very low phenyl
alcohol concentrations. The position of one type of resonance, which on the basis
of spectroscopic selection rules is denoted as Delta(0), is related to the
solvent polarity of the radicals' environment. The results derived from Delta(0)
measurements reveal a systematic trend where the increasing chain length of the
phenyl alcohol results in a deeper immersion of the phenyl ring of the alcohol
into the surfactant bilayer with the OH group anchored at the interface. In
addition, the data suggest partial penetration of water molecules into the
bilayer. Furthermore, data ensuing from a second resonance (called Delta(1),
which is dependent upon the degree of confinement of the radical within the
surfactant aggregate structure) indicates not only that the phenyl alcohol
resides in an anisotropic environment, (i.e. that the host molecule is unable to
undergo full 3-D reorientation on a timescale of 50 ns), but the resonance line
widths indicate that the radicals are undergoing fast rotation about a particular
axis, in this instance about the first C-C substituent bond at the phenyl ring.
Detailed analysis of these Delta(1) line shapes suggests that other types of
motion involving reorientation of the above rotation axis are also present. At
room temperature, the hydrocarbon chains of the double layers form an aggregate
state commonly referred to as the L(beta) phase, where the motions of surfactant
alkyl chains are effectively frozen out. These chains melt on heating over a
temperature range which is solution composition dependent (ca. 51 to 67 degrees
C), but in all cases leading to a liquid-like disordered hydrocarbon regime
whilst retaining the overall lamellar structure (and in this state is termed
L(alpha)). Above the L(alpha)/L(beta) chain ordering phase transition the tracer
molecules reside within the bilayer, but below this transition (and depending on
their water-oil solubility) they are completely or partly expelled. This
interpretation is further supported by Heisenberg spin exchange experiments. The
water-bilayer partitioning reflects both typical classical and nonclassical
hydrophobic solvation depending on temperature and chain length of phenyl
alcohols.
PMID- 17043716
TI - Interfacial pH and surface pKa of a thioctic acid self-assembled monolayer.
AB - A self-assembled acid-functionalised monolayer on a gold surface has an
interfacial pH 2.93 more acidic than the bulk and surface pK(a) very similar to
that of the free acid.
PMID- 17043717
TI - Theoretical modeling and interpretation of X-ray absorption spectra of liquid
water.
AB - We report extensive calculations to examine the capability of theory to explain
the XAS spectra of liquid water. Several aspects that enter the theoretical model
are addressed, such as the quantum mechanical methods, the statistics and the XAS
model. As input into our quantum mechanical calculations we will use structural
information on liquid water obtained from first principles and from classical
molecular dynamics simulations. As XAS models, we will examine the full core hole
and the half core hole approximations to transition state theory. The quantum
mechanics is performed on the basis of density functional theory. We conclude
from this study that recent experimental results are fully consistent with, and
can be completely explained by, present day theory, in particular, the pre-edge
peak is reproduced. We also find that the average bond coordination in liquid
water is 3.1 and that the assertion in a recent paper that the hydrogen bond
number is much less than that cannot be substantiated. Our calculations emphasize
that further advances in our understanding of water can only be made by more
sophisticated spectroscopy with significantly increased resolution.
PMID- 17043718
TI - Accurate potential energy curves for F(-)-Rg (Rg = He-Rn): spectroscopy and
transport coefficients.
AB - High-quality ab initio potential energy curves are presented for the F(-)-Rg
series (Rg = He-Rn). Calculations are performed at the CCSD(T) level of theory,
employing d-aug-cc-pV5Z quality basis sets, with "small core" relativistic
effective core potentials being used for Kr-Rn. The quality of the curves is
judged by agreement with recent high-level calculations in the case of F(-)-He
and F(-)-Ne and by excellent agreement with mobility data for the systems F(-)-Rg
(Rg = He-Xe). Except for these recent high-level calculations on the two lightest
systems, we are able to deduce that all other previous potentials for the whole
set of these systems are inadequate. We also present spectroscopic information
for the titular species, derived from our potential energy curves.
PMID- 17043719
TI - (2 + 1) REMPI spectroscopy of the NO-CO, NO-N2, and NO-{N(2), Ar} van der Waals
complexes in the region of the 4s and 3d Rydberg states.
AB - We have collected (2 + 1) Resonance-Enhanced Multiphoton Ionization (REMPI)
spectra of van der Waals complexes in which a NO molecule is attached to either
CO, N(2), or both N(2) and Ar. The energy region probed corresponds to electronic
transitions of uncomplexed NO(X(2)Pi) to the 4s and 3d Rydberg states, and we
discuss the observed spectra in light of the expected perturbations to these
electronic levels induced by complexation. We employ a model in which the van der
Waals partners are assumed to reside within the Rydberg orbital, and discuss the
importance of core penetration in the description of the electronic structure. By
performing calculations on NO(+) interacting with both N(2) and Ar, we identify
the global minimum as being a non-planar structure. Further, the N(2) and Ar are
found to interact with the NO(+) largely independently, and we find some evidence
for this from the REMPI spectrum of NO-{N(2), Ar}.
PMID- 17043720
TI - VUV electronic state spectroscopy of 1,1-difluoroethene and difluorochloromethane
by high resolution synchrotron radiation.
AB - High resolution VUV photoabsorption spectra of 1,1-difluoroethene (C(2)H(2)F(2))
and difluorochloromethane (CF(2)HCl) are reported in the wavelength range 115-200
nm (10.8-6.2 eV). New photoabsorption features are observed in C(2)H(2)F(2) and
some Rydberg and vibrational assignments are proposed for the first time.
Evidence for a weak vibrational pattern in CF(2)HCl is discussed here for the
first time. Absolute cross section values have been obtained allowing photolysis
lifetimes to be derived in the Earth's troposphere and stratosphere.
PMID- 17043721
TI - Reactions of OH and NO radicals with 1,1-dichloroethylene in argon matrices. FTIR
and theoretical studies.
AB - HONO/1,1-dichloroethylene/Ar matrices were subjected to UV radiation (lambda >
340 nm) from a medium pressure mercury lamp. The products of the photolysis were
studied experimentally by means of FTIR spectroscopy and theoretically using the
ab initio MP2 method. Two conformers of 2-nitroso-2,2-dichloroethanol molecule
have been identified as the final products of the double addition reaction of the
OH, NO radicals to 1,1-dichloroethylene. The additional reactive species observed
in the matrix is tentatively identified as an 1,1-dichloro-2-hydroxyethyl
radical, an intermediate formed by single addition of OH to 1,1-dichloroethylene.
The three photoproducts have been identified and observed for the first time. The
identities of the products have been justified by comparison with the experiments
with deuterated DONO and by performing concentration and annealing studies as
well as by reference to the spectral data of related molecules. The results of
the quantum mechanical calculations confirmed both the assignment of the new
molecules and mechanism of the reaction observed in our experiment.
PMID- 17043722
TI - Hydration profiles of aromatic amino acids: conformations and vibrations of L
phenylalanine-(H2O)n clusters.
AB - IR-UV double resonance spectroscopy and ab initio calculations were employed to
investigate the structures and vibrations of the aromatic amino acid, L
phenylalanine-(H(2)O)(n) clusters formed in a supersonic free jet. Our results
indicate that up to three water molecules are preferentially bound to both the
carbonyl oxygen and the carboxyl hydrogen of L-phenylalanine (L-Phe) in a bridged
hydrogen-bonded conformation. As the number of water molecules is increased, the
bridge becomes longer. Two isomers are found for L-Phe-(H(2)O)(1), and both of
them form a cyclic hydrogen-bond between the carboxyl group and the water
molecule. In L-Phe-(H(2)O)(2), only one isomer was identified, in which two water
molecules form extended cyclic hydrogen bonds with the carboxyl group. In the
calculated structure of L-Phe-(H(2)O)(3) the bridge of water molecules becomes
larger and exhibits an extended hydrogen-bond to the pi-system. Finally, in
isolated L-Phe, the D conformer was found to be the most stable conformer by the
experiment and by the ab initio calculation.
PMID- 17043723
TI - Impact on lipid membrane organization by free branched-chain fatty acids.
AB - Here, we exploit the non-invasive techniques of solid-state NMR (nuclear magnetic
resonance) and differential scanning calorimetry (DSC) to study the effect of
free iso and ante-iso branched chain fatty acids (BCFAs) on the physicochemical
properties of lipid membranes. Free fatty acids are present in biological
membranes at low abundance, but can influence the cellular function by modulating
the membrane organization. Solid state NMR spectra of
dimyristoylphosphatidylcholine (DMPC) lipid membranes containing either free 12
methyltetradecanoic acid (a15:0) or free 13-methyltetradecanoic acid (i15:0),
show significant differences in their impact on the lipid bilayer. Chain order
profiles obtained by deuterium NMR on fully deuterated DMPC-d(67) bilayers
revealed an ordering effect induced by both fatty acids on the hydrophobic
membrane core. This behavior was also visible in the corresponding DSC
thermograms where the main phase transition of DMPC bilayers-indicative of the
hydrophobic membrane region-was shifted to higher temperatures, with the iso
isomer triggering more pronounced changes as compared to the ante-iso isomer.
This is probably due to a higher packing density in the core of the lipid
bilayer, which causes reduced diffusion across membranes. By utilizing the
naturally occurring spin reporters nitrogen-14 and phosphorus-31 present in the
hydrophilic DMPC headgroup region, even fatty acid induced changes at the
membrane interface could be detected, an observation reflecting changes in the
lipid headgroup dynamics.
PMID- 17043724
TI - HCl and DCl: a case study of different approaches for determining photo
fractionation constants.
AB - The photoabsorption cross sections of HCl and DCl are calculated using the
reflection principle and time dependent wavepacket propagation methods. The
absorption cross sections are compared to high precision experimental absorption
cross sections from the literature and the different results given by the methods
are discussed. The results of the calculations emphasize the important roles that
photodissociation dynamics and the change in transition dipole moment with
internuclear distance play in isotopic fractionation. The wave number dependent
fractionation constants have been determined. The process fractionation constant
has been calculated in the Venusian atmosphere where photo-fractionation leads to
enrichment in deuterium through loss of hydrogen to space. At an altitude of 70
km the process fractionation constant was found to be epsilon(p) = -344 per
thousand and epsilon(p) = -256 per thousand for the experimental and the
reflection principle methods, respectively. At the top of the atmosphere the
process fractionation constant was evaluated to be epsilon(p) = -32 per thousand,
epsilon(p) = -20 per thousand and epsilon(p) = -40 per thousand using the
experimental data, the wavepacket and the reflection principle methods,
respectively. Using the Rayleigh distillation formula it is concluded that HCl at
the top of the Venusian atmosphere is fractionated (enriched in D) relative to
the bulk composition prior to photolysis.
PMID- 17043725
TI - Adsorption of CO2 on oxidized, defected, hydrogen and oxygen covered rutile (1 x
1)-TiO2(110).
AB - Presented are initial, S(0) and coverage, Theta, dependent S(Theta), adsorption
probability measurements of CO(2) as a function of impact energy, E(i) = 0.12-1.3
eV, adsorption temperature, T(s) = 85-300 K, hydrogen and oxygen pre-exposure, as
well as density of defects, Gamma, as varied by annealing (T = 600-900 K) and
Ar(+) ion sputtering (dose chi(Ar) at 600 eV at 85 K) of a rutile (1 x 1)
TiO(2)(110) surface. The defect densities were qualitatively characterized by
thermal desorption spectroscopy (TDS) of CO(2). The CO(2) TDS curves consisted of
two structures that can be assigned to adsorption on pristine and oxygen vacancy
sites, in agreement with earlier studies. S(0) decreased linearly with E(i) and
was independent of T(s). The adsorption dynamics were dominated by the effect of
precursor states leading to Kisliuk-like shapes over the E(i) and T(s) range
studied. Oxygen vacancy sites reduced S(0) of CO(2). Preadsorbed oxygen blocked
preferentially defect sites, which led to an increase in S(0). Hydrogen
preadsorption results in physical site blocking with decreased S(0) as H
preexposure increased, while the shape of S(Theta) curves was conserved. In
contrast to oxygen, hydrogen does not adsorb preferentially on defect sites. The
adsorption probability data were parameterized by analytic functions (Kisliuk
model) and by Monte Carlo simulations (MCSs).
PMID- 17043726
TI - Elucidation of the molecular structure of hydrated vanadium oxide species by X
ray absorption spectroscopy: correlation between the V...V coordination number
and distance and the point of zero charge of the support oxide.
AB - The effect of the point of zero charge (PZC) of the support oxide (Al(2)O(3),
Nb(2)O(5), SiO(2) and ZrO(2)) on the molecular structure of hydrated vanadium
oxide species has been investigated with EXAFS spectroscopy for low-loaded
vanadium oxide catalysts. It was found that the degree of clustering (i.e., the
V[dot dot dot]V coordination number) and the V...V distance increase with
decreasing PZC of the support oxide; i.e., Al(2)O(3) (8.7) < ZrO(2) (7) <
Nb(2)O(5) (3.3) < SiO(2) (2). Upon hydration the silica-supported vanadium oxide
exhibited a clear alteration in the position of the oxygen atoms surrounding the
central vanadium atom and the number of oxygen atoms around vanadium increased to
five. In contrast, only minor changes in the molecular structure were detected
for the alumina-, niobia- and zirconia-supported vanadium oxide catalysts. Based
on a detailed analysis of the EXAFS data a semi-quantitative distribution of
vanadium oxide species present on the surface of the different support oxides can
be obtained, which is in good agreement with earlier characterization studies
primarily making use of Raman spectroscopy.
PMID- 17043728
TI - PET with 18F-DOPA in the imaging of parathyroid adenoma in patients with primary
hyperparathyroidism. A pilot study.
AB - Preoperative localization of parathyroid adenomas (PA) can shorten operation time
and improve curative rate; it becomes especially important in minimally invasive
surgical techniques. AIM of this study was to investigate whether positron
emission tomography (PET) with 3-,4-dihydroxy-6- (18) F-fluorophenylalanine (
(18) F-DOPA), which showed very promising results in other neuroendocrine
tumours, also helps to localize PA. PATIENTS, METHODS: Eight patients with proven
primary hyperparathyroidism were studied preoperatively with PET. Seven also
underwent scintigraphy with (99m) Tc-MIBI and ultrasonography of the neck. All
patients were operated and the histological finding was used as a gold standard.
RESULTS: All eight patients had a histologically proven PA. None of the PA showed
any detectable uptake of (18) F-DOPA. However, ultrasonography detected 5/7 PA,
scintigraphy detected 3/7 PA. CONCLUSION: These results suggest that PET with
(18) F-DOPA is not useful in the detection of PA in patients with primary
hyperparathyroidism.
PMID- 17043729
TI - Gender dependent rate of metabolism of the opioid receptor-PET ligand
[18F]fluoroethyldiprenorphine.
AB - AIM: The morphinane-derivate 6-O-(2-[(18)F]fluoroethyl)-6-O
desmethyldiprenorphine ([(18)F]FDPN) is a nonselective opioid receptor ligand
currently used in positron emission tomography (PET). Correction for plasma
metabolites of the arterial input function is necessary for quantitative
measurements of [(18)F]FDPN binding. A study was undertaken to investigate if
there are gender dependent differences in the rate of metabolism of [(18)F]FDPN.
METHODS: The rate of metabolism of [(18)F]FDPN was mathematically quantified by
fitting a bi-exponential function to each individual's dynamic metabolite data.
RESULTS: No statistically significant gender differences were found for age,
weight, body mass index or dose. However, significant differences (p < 0.01) in
two of the four kinetic parameters describing the rate of metabolism were found
between the two groups, with women metabolizing [(18)F]FDPN faster than men.
These differences were found in the contribution of the fast and slow kinetic
components of the model describing the distribution of radioactive species in
plasma, indicating a higher rate of enzyme-dependent degradation of [(18)F]FDPN
in women than in men. CONCLUSION: The findings reinforce the need for
individualized metabolite correction during [(18)F]FDPN-PET scans and also
indicate that in certain cases, grouping according to gender could be performed
in order to minimize methodological errors of the input function prior to kinetic
analyses.
PMID- 17043730
TI - Thallium-201 scan in evaluating thyroid nodules following equivocal fine-needle
aspiration cytology.
AB - The AIM of this prospective study was to evaluate the usefulness of the thallium
201 ( (201) Tl) thyroid scan in the detection of malignancy in cold thyroid
nodules whose status was equivocal following palpation fine-needle aspiration
cytology (FNAC). PATIENTS, METHODS: Fifty-one patients with clinically palpable
solitary cold thyroid nodules classified as non-diagnostic or suspicious
following biopsy underwent (201) Tl thyroid scans. Each scan was performed 15 min
(early scan) and 3 h (delayed scan) after an intravenous administration of 74 MBq
(201) Tl. Thallium uptake in the nodules was visually assessed and scored on a
three point scale, with a grade of three defining malignancy. All patients
underwent surgery and the histopathology of nodule tissues were compared with
results of the scans. RESULTS: Fifty-one nodules were examined. Forty were benign
and 11 were malignant. For early scans, the diagnostically relevant parameters
were: sensitivity (100%), specificity (75%), and accuracy (80%). Corresponding
findings for the delayed scan were: 91%, 98%, and 96%. CONCLUSION: The (201) Tl
scan is useful for detecting malignancy in cold thyroid nodules classified as
nondiagnostic or suspicious lesions by FNAC.
PMID- 17043731
TI - What is the best pre-therapeutic dosimetry for successful radioiodine therapy of
multifocal autonomy?
AB - PURPOSE: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies
(MFA) is a problem as therapeutic outcome may be worse than in other kinds of
autonomies. We compared different dosimetric concepts in our patients. PATIENTS,
METHODS: Data from 187 patients who had undergone RIT for MFA (Marinelli
algorithm, volumetric compromise) were included in the study. For calculation,
either a standard or a measured half-life had been used and the dosimetric
compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated
by 2 alternative concepts and compared to therapeutic success achieved (concept
of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based
adaptation of target dose on total thyroid volume). RESULTS: If a standard half
life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n
= 143). If a measured half-life was used the success rate was 93.1% (13,6%
hypothyroidism, n = 44). These differences were statistically not significant,
neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid
after therapy (ANOVA, all p > 0.05). The alternative dosimetric concepts would
have resulted either in significantly lower organ doses (TcTUs-based calculation
of autonomous volume; 80.76 +/- 80.6 Gy versus 125.6 +/- 46.3 Gy; p < 0.0001) or
in systematic over-treatment with significantly higher doses (TcTUs-adapted
concept; 164.2 +/- 101.7 Gy versus 125.6 +/- 46.3 Gy; p = 0.0097). CONCLUSIONS:
TcTUsbased determination of the autonomous volume should not be performed, the
TcTUs-based adaptation of the target dose will only increase the rate of
hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for
RIT of MFA. If so, individual therapeutic activities may be calculated based on
thyroid size corrected to the 24h ITUs without using Marinelli's algorithm.
PMID- 17043732
TI - Lithium as an adjunct to radioiodine therapy in Graves' disease for prolonging
the intrathyroidal effective half-life of radioiodine. Useful or not?
AB - AIM: Evaluation of intrathyroidal kinetics of radioiodine with and without
lithium as adjunct with respect to the increase in radiation dose delivered to
the thyroid. PATIENTS, METHODS: 267 patients in three groups were included in the
study. Group I with 227 patients served as control group, Group II with 21
patients and Group III with 19 patients were distinguished by an intrathyroidal
half-life of radioiodine below 3.5 days in the diagnostic test. Patients in Group
III received 885 mg lithium carbonate a day for 2 weeks as adjunct to radioiodine
therapy. Both diagnostic and therapeutic radioiodine kinetics were followed up by
at least 10 uptake measurements within a minimum of 48 h. Kinetics of radioiodine
were defined mathematically as balance of the thyroidal iodine intake and
excretion by a two-compartment model. RESULTS: Under therapy the maximum uptake
of radioiodine was reduced by nearly 10% in all groups, in Group I, the effective
half-life as well as the product of maximum uptake x effective half-life as an
equivalent of radiation dose independent of thyroid volume was lowered in the
same magnitude. In Group II, the energy-dose equivalent remained constant under
therapy. With adjunct lithium in Group III, the effective half-life was prolonged
significantly by factor 1.61 +/- 0.49 and the volume-independent energy-dose
equivalent by factor 1.39 +/- 0.37. No severe side effects of lithium were
observed. CONCLUSION: Using lithium as adjunct to radioiodine therapy increases
the radiation dose delivered to the thyroid by 39% on average and nearly 30% of
radioiodine activity can be saved in these patients. Lithium is recommended in
patients with very short effective half-life in the diagnostic test in order to
reduce the activity required and whole-body radiation dose.
PMID- 17043733
TI - Combined 18F-FDG-PET/CT imaging of the head and neck. An approach to metal
artifact correction.
AB - PET/CT imaging is particularly promising for head/neck malignancies, but dental
implants lead to biased CT attenuation and PET activity values following CT-based
attenuation correction (CT-AC). OBJECTIVE: Here, we implement a metal artifact
correction procedure (MAR) as part of the CT-AC for PET/CT imaging. RESULTS:
Phantom studies indicate a maximum quantitative bias in CT and PET of 1000 HU and
30 %, which is reduced to 230 HU and 6 %, respectively following MAR. These
results were verified in selected patients. CONCLUSION: Artifacts and biases from
dental implants can be reduced in PET/CT imaging by applying a simple MAR as part
of the CT-AC.
PMID- 17043734
TI - Biological dosimetry after yttrium-90 citrate colloid radiosynoviorthesis.
AB - Radiosynoviorthesis (RSO) with the ss-particle-emitting nuclide yttrium-90 is an
established concept for the treatment of persistent synovitis of the knee joint.
The AIM of this study was to investigate the biological radiation effect on the
basis of a characteristic radiation parameter. PATIENTS, METHODS: After RSO
procedures with yttrium-90 citrate colloid and subsequent immobilisation of the
knee, blood specimens of 10 patients were collected immediately before RSO and 11
to 13 days after the intervention. The yield of dicentric chromosomes in the
lymphocytes was determined exclusively in metaphases of the first cell cycle in
vitro. In addition, activity leakage was measured by wholebody bremsstrahlung
scintigraphy. RESULTS: No statistically significant increase in the number of
dicentric chromosomes (26 before treatment and 34 after treatment) in 20 192
cells analyzed from the 20 blood samples could be found as a result of RSO.
However, the analysis of at least 1000 cells per blood sample demonstrates a
tendency for a biological radiation effect in the blood of patients on the basis
of this characteristic radiation parameter. Two of the 10 RSO patients had
undergone a second RSO using yttrium-90 citrate, whereby one patient displayed
activity transport out of the knee joint, amounting to 6 MBq. Only for him a
radiation effect (about 130 mGy per single RSO) could be calculated by biological
dosimetry. CONCLUSION: Since in general, based on the analysis of dicentric
chromosomes in at least 1000 lymphocytes per individual, detection limits for
groups of persons after long-term exposures to low-LET radiation of 50-100 mGy
are possible, we assume that RSO with yttrium-90 should be associated with a low
whole-body radiation exposure.
PMID- 17043735
TI - [Evil radioactivity. Subjective perception of radioactivity in patients with
thyroid disease prior to treatment with radioiodine].
AB - AIM: We assess the perspective of patients with thyroid disease towards radiation
and radioactivity by means of a cultural-anthropological approach based on
qualitative measures and quantitative scores. From the interviews with the
patients we evaluate as to how much radioactivity is accepted as an abstract term
or as a benefit within the medical context. PATIENTS, METHODS: 68 patients with
autonomously functioning thyroid lesions (35 women, 33 men, 32-81 years) were
included in this study. All patients were interviewed in an open dialogue with
the principal investigator. Patients were asked to describe their attitude
towards radioactivity in general and towards radioiodine therapy in particular.
Patients were asked to use a scoring system (1 = positive, 5 = negative) to
quantify their attitudes. RESULTS: The responses of all patients towards
radioactivity in general were heterogeneous with most responses reflecting a
negative perception. Many patients expressed their associated fears about atomic
energy, malignant diseases and radioactive contamination. The scoring system
reflected a mostly negative opinion base. However, patients became more positive
once they assumed an immediate benefit of radioactivity for the treatment of
their own disease (p = 0.01). CONCLUSIONS: Knowing about significant differences
in patient's perception about radioactivity in general or in the clinical context
may help to optimise and tailor the initial, pre-therapeutical interview towards
the patient.
PMID- 17043736
TI - Quantification of aortic valve stenosis in MRI-comparison of steady-state free
precession and fast low-angle shot sequences.
AB - We compared two different magnetic resonance (MR) sequences [steady-state free
precession (SSFP) and gradient echo fast low-angle shot (FLASH)] for the
assessment of aortic valve areas in aortic stenosis using transesophageal
echocardiography (TEE) as the standard of reference. Thirty-two patients with
known aortic stenosis underwent MR (1.5 T) using a cine SSFP sequence and a cine
FLASH sequence. Planimetry was performed in cross-sectional images and compared
to the results of the TEE. In seven patients the grade of stenosis was
additionally assessed by invasive cardiac catheterization (ICC). The mean aortic
valve area measured by TEE was 0.97+/-0.19 mm(2), 1.00+/-0.25 mm(2) for SSFP and
1.25+/-0.23 mm(2) based on FLASH images. The mean difference between the valve
areas assessed based on SSFP and TEE images was 0.15+/-0.13 cm(2) (FLASH vs TEE:
0.29+/-0.17 cm(2)). Bland-Altman analysis demonstrated that measurements using
FLASH images overestimated the aortic valve area compared to TEE. Comparing ICC
with MRI and TEE, only a weak to moderate correlation was found (ICC vs TEE:
R=0.52, p=0.22; ICC vs SSFP: R=0.20, p=0.65; ICC vs FLASH: R=0.16, p=0.70).
Measurements of the aortic valve area based on SSFP images correlate better with
TEE compared to FLASH images.
PMID- 17043737
TI - Imaging oxygenation of human tumours.
AB - Tumour hypoxia represents a significant challenge to the curability of human
tumours leading to treatment resistance and enhanced tumour progression. Tumour
hypoxia can be detected by non-invasive and invasive techniques but the inter
relationships between these remains largely undefined. (18)F-MISO and Cu-ATSM
PET, and BOLD-MRI are the lead contenders for human application based on their
non-invasive nature, ease of use and robustness, measurement of hypoxia status,
validity, ability to demonstrate heterogeneity and general availability, these
techniques are the primary focus of this review. We discuss where developments
are required for hypoxia imaging to become clinically useful and explore
potential new uses for hypoxia imaging techniques including biological conformal
radiotherapy.
PMID- 17043738
TI - Improved visualization of collateral ligaments of the ankle: multiplanar
reconstructions based on standard 2D turbo spin-echo MR images.
AB - The purpose of the study was to evaluate the visualization of the collateral
ankle ligaments on multiplanar reconstructions (MPR) based on standard 2D turbo
spin-echo images. Coronal and axial T2-weighted turbo spin-echo and MPR angled
parallel to the course of the ligaments of 15 asymptomatic and 15 symptomatic
ankles were separately analyzed by two musculoskeletal radiologists. Image
quality was assessed in the asymptomatic ankles qualitatively. In the symptomatic
ankles interobserver agreement and reader confidence was determined for each
ligament. On MPR the tibionavicular and calcaneofibular ligaments were more
commonly demonstrated on a single image than on standard MR images (reader 1: 13
versus 0, P=0.002; reader 2: 14 versus 1, P=0.001 and reader 1: 13 versus 2,
P=0.001; reader 2: 14 versus 0, P<0.001). The tibionavicular ligament was
considered to be better delineated on MPR by reader 1 (12 versus 3, P=0.031). In
the symptomatic ankles, reader confidence was greater with MPR for all ligaments
except for the tibiocalcanear ligament (both readers) and the anterior and
posterior talofibular ligaments (for reader 2). Interobserver agreement was
increased with MPR for the tibionavicular ligament. Multiplanar reconstructions
of 2D turbo spin-echo images improve the visualization of the tibionavicular and
calcaneofibular ligaments and strengthen diagnostic confidence for these
ligaments.
PMID- 17043739
TI - Comparison of transperineal and transabdominal ultrasound in the assessment of
voluntary pelvic floor muscle contractions and functional manoeuvres in continent
and incontinent women.
AB - Transperineal (TP) and transabdominal (TA) ultrasounds were used to assess
bladder neck (TP) and bladder base (TA) movement during voluntary pelvic floor
muscle (PFM) contraction and functional tasks. A sonographer assessed 60
asymptomatic (30 nulliparous, 30 parous) and 60 incontinent (30 stress, 30 urge)
women with a mean age of 43 (SD=7) years, BMI of 24 (SD=4) kg m2 and a median
parity of 2 (range, 0-5), using both ultrasound methods. The mean of three
measurements for bladder neck and bladder base (sagittal view) movement for each
task was assessed for differences between the groups. There were no differences
in bladder neck (p=0.096) or bladder base (p=0.112) movement between the four
groups during voluntary PFM contraction but significant differences in bladder
neck (p<0.004) and a trend towards differences in bladder base (p=0.068) movement
during Valsalva and abdominal curl manoeuvre. During PFM contraction, there was a
strong trend for the continent women to have greater bladder neck elevation
(p=0.051), but no difference in bladder base movement (p=0.300), when compared to
the incontinent women. The incontinent women demonstrated increased bladder neck
descent during Valsalva and abdominal curl (p<0.001) and bladder base descent
during Valsalva (p=0.021). The differences between the groups were more marked
during functional activities, suggesting that comprehensive assessment of the PFM
should include functional activities as well as voluntary PFM contractions. TP
ultrasound was more reliable and takes measures from a bony landmark when
compared to TA ultrasound, which lacks a reference point for measurements. TA
ultrasound is less suitable for PFM measures during functional manoeuvres and
comparisons between subjects. Few subjects were overweight so the results may not
be valid in an obese population.
PMID- 17043740
TI - Interrater reliability of assessing levator ani muscle defects with magnetic
resonance images.
AB - The objective of this study is to determine interrater reliability of assessing
pubovisceral levator ani muscle defects with magnetic resonance images. Normal
pubovisceral muscle was assigned a grade of 0; PVM defects were graded as mild=1
(less than half missing), moderate=2 (more than half missing), and severe=3
(total or near total loss). Among six pairs of examiners, percent agreement and
weighted kappa coefficients were calculated to determine agreement between pairs
of examiners and among all examiners (i.e., "overall"). For unilateral scoring,
exact agreement was found in 83.7%, and differences of one, two, and three grades
were found in 14.7, 1.5, and 0.1%, respectively. For bilateral scoring, exact
agreement and differences of one, two and three grades were found in 75.4, 15.9,
6.9, and 1.6%, respectively. Thus, exact agreement or a one-point difference was
reached in 91.3% of cases. When defect status was categorized as none/normal,
minor, and major, the overall weighted kappa coefficient was 0.86 (95% CI 0.83,
0.89). There was variation among examiner pairs with unilateral (p=0.002) and
bilateral (p=0.02) scoring, but not when defect status was categorized as
none/normal, minor, and major (p=0.59). There was agreement to within one point
in 91% of cases when six examiner pairs scored levator ani defects on a seven
point scale. Examiner pairs discriminated injury similarly when defect status was
categorized as normal/none, minor, or major.
PMID- 17043741
TI - The impact of pregnancy and childbirth in the urethra of female rats.
AB - The aim of this study was to evaluate the modifications in the amount of
collagen, muscular, and elastic fibers in the mid-urethra of adult female rats
during the pregnancy and after the natural childbirth, cesarean, and after
simulated trauma of childbirth. The authors evaluated the histomorphometric
aspects (collagen, muscular, and elastic fibers) in the mid-urethra of 70 animals
distributed in seven groups: group 1 (n = 10)--control, group 2 (n = 10)-
pregnant female rats, group 3 (n = 10)--female rats submitted to cesarean, group
4 (n = 10)--female rats with natural childbirth, group 5 (n = 10)--virgin female
rats with simulated trauma of childbirth, group 6 (n = 10)--female rats submitted
to cesarean followed by simulation of childbirth trauma, and group 7 (n = 10)-
female rats with natural childbirth followed by simulation of childbirth trauma.
The average concentration of collagen and elastic fibers and the
collagen/muscular fiber correlation in groups 1, 2, and 3 were similar and
significantly inferior to groups 4, 5, 6, and 7. The average of muscular fibers
was similar in groups 1, 2, and 3 and significantly superior to groups 4, 5, 6,
and 7. Pregnancy and cesarean did not induce alterations in collagen, muscular,
and elastic fibers. However, the vaginal delivery and simulation of childbirth
trauma determined the decrease in muscular fibers and the increase in collagen
and elastic fibers and the correlation collagen/muscular fiber.
PMID- 17043742
TI - A genetic linkage map of Pacific white shrimp (Litopenaeus vannamei): sex-linked
microsatellite markers and high recombination rates.
AB - Pacific white shrimp (Litopenaeus vannamei) is the leading species farmed in the
Western Hemisphere and an economically important aquaculture species in China. In
this project, a genetic linkage map was constructed using amplified fragment
length polymorphism (AFLP) and microsatellite markers. One hundred and eight
select AFLP primer combinations and 30 polymorphic microsatellite markers
produced 2071 markers that were polymorphic in either of the parents and
segregated in the progeny. Of these segregating markers, 319 were mapped to 45
linkage groups of the female framework map, covering a total of 4134.4 cM; and
267 markers were assigned to 45 linkage groups of the male map, covering a total
of 3220.9 cM. High recombination rates were found in both parental maps. A sex
linked microsatellite marker was mapped on the female map with 6.6 cM to sex and
a LOD of 17.8, two other microsatellite markers were also linked with both 8.6 cM
to sex and LOD score of 14.3 and 16.4. The genetic maps presented here will serve
as a basis for the construction of a high-resolution genetic map, quantitative
trait loci (QTLs) detection, marker-assisted selection (MAS) and comparative
genome mapping.
PMID- 17043743
TI - Population structure of the boll weevil in cotton fields and subtropical forests
of South America: a bayesian approach.
AB - The main goal of this contribution is to investigate the genetic structure of
boll weevil populations from South America (Argentina and Brazil) and to make
further comparisons with a putative source population from USA. Samples were
collected in a Paranaense forest under reserve protection, cotton fields and non
cultivated areas. Data from anonymous molecular markers were analysed using both
traditional methods of population genetics and Bayesian approaches. Results help
to support a previous hypothesis on the presence of two lineages of boll weevil
populations in South America: one with characteristics of recent invaders and the
other with characteristics of ancient populations. The sample from Urugua-i
Provincial Park (Misiones, Argentina) shows the highest percentage of polymorphic
loci, the highest values of mean heterozigosity, and the largest number of
population-specific alleles, all being typical features of ancient populations.
Furthermore, the Urugua-i sample shows two gene pools occurring in sympatry,
probably as a consequence of a secondary contact. The remaining samples reveal
not only lower percentages of polymorphic loci and heterozygosity values, but
also an almost negligible presence of specific alleles. Bayesian methods also
suggest the occasional migration of some individuals of ancient lineages from
their natural habitats in fragments of the Paranaense forest into cotton fields,
and vice versa.
PMID- 17043744
TI - Gene expression divergence and the origin of hybrid dysfunctions.
AB - Hybrids between closely related species are often sterile or inviable as a
consequence of failed interactions between alleles from the different species.
Most genetic studies have focused on localizing the alleles associated with these
failed interactions, but the mechanistic/biochemical nature of the failed
interactions is poorly understood. This review discusses recent studies that may
contribute to our understanding of these failed interactions. We focus on the
possible contribution of failures in gene expression as an important contributor
to hybrid dysfunctions. Although regulatory pathways that share elements in
highly divergent taxa may contribute to hybrid dysfunction, various studies
suggest that misexpression may be disproportionately great in regulatory pathways
containing rapidly evolving, particularly male-biased, genes. We describe three
systems that have been analyzed recently with respect to global patterns of gene
expression in hybrids versus pure species, each in Drosophila. These studies
reveal that quantitative misexpression of genes is associated with hybrid
dysfunction. Misexpression of genes has been documented in sterile hybrids
relative to pure species, and variation in upstream factors may sometimes cause
the over- or under-expression of genes resulting in hybrid sterility or
inviability. Studying patterns of evolution between species in regulatory
pathways, such as spermatogenesis, should help in identifying which genes are
more likely to be contributors to hybrid dysfunction. Ultimately, we hope more
functional genetic studies will complement our understanding of the genetic
disruptions leading to hybrid dysfunctions and their role in the origin of
species.
PMID- 17043745
TI - 1H, 13C, and 15N NMR assignment of the master Rep protein nuclease domain from
the nanovirus FBNYV.
PMID- 17043746
TI - Solution structure of calponin homology domain of Human MICAL-1.
PMID- 17043747
TI - Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of
metalloproteinase (TIMP) in cerebral cavernous malformations: immunohistochemical
analysis of MMP-2, -9 and TIMP-2.
AB - OBJECT: Hemorrhage from cerebral vascular malformations such as cerebral
cavernous malformation (CCM) can result in significant mortality and morbidity,
but its underlying mechanism is undetermined. Excessive degradation of the
vascular matrix by matrix metalloproteinases (MMPs), proteolytic enzymes that
degrade all the components of extracellular matrix, can lead to instability of
the vascular structure and can thereby cause bleeding. Thus we examined the
expression of MMPs and tissue inhibitors of metalloproteinase (TIMP) in CCM.
PATIENTS AND METHODS: We performed immunohistochemistry for MMP-2, -9, and TIMP-2
using Paraffin-embedded sections of the surgical specimens obtained from seven
patients with CCM. All patients had a history of hemorrhage from CCM. FINDINGS:
In all patients (7/7, 100%), MMP-2 and -9 were strongly expressed in endothelial
cells of CCMs. Endothelial expression of TIMP-2 was also evident in all seven
patients. In contrast, MMP-2, -9 and TIMP-2 were not identified in adjacent
normal brain tissue. CONCLUSION: We found that CCM showed the increased
endothelial expression of MMP-2, -9, and TIMP-2. Endothelial expression of MMPs
and/or TIMP may affect the vascular matrix stability, and thus can contribute to
hemorrhage from CCM.
PMID- 17043748
TI - Ruptured intracranial aneurysm following gamma knife surgery for acoustic
neuroma.
AB - A-63-year-old woman underwent gamma knife surgery (GKS) for acoustic neuroma. Six
years later, she suffered sudden onset of severe headache followed by a
disturbance of consciousness and subarachnoid haemorrhage due to a ruptured
aneurysm originating from the distal anterior inferior cerebellar artery. The
aneurysm was not located at a branching site and was included within the
radiation field. The aneurysm was treated by endovascular embolization, and now,
15 months later, the patient has recovered satisfactorily. This is the first
report of aneurysm formation following GKS for acoustic neuroma.
PMID- 17043749
TI - Microsatellite analysis of Japanese sea cucumber, Stichopus (Apostichopus)
japonicus, supports reproductive isolation in color variants.
AB - The genetic relationship among the three color variants (Red, Green, and Black)
of the Japanese sea cucumber, S. japonicus, was investigated using 11
microsatellite markers. Genetic differentiation testing among the three sympatric
color types showed the strong heterogeneity of Red (p<0.001), while no
significant difference was observed between Green and Black (p=0.301 to 0.961).
UPGMA trees constructed from 10 sample lots from 5 localities showed two distinct
clusters, one from the Red types and the other from the Green and Black types. In
addition, the sympatric Green and Black formed one subcluster with strong
bootstrap support at each locality. These results indicate the separate species
status of Red and the other color types, and also support the population identity
of sympatric Green and Black.
PMID- 17043751
TI - Prolonged anti-hypertensive effects of oral sitaxsentan, a selective ET(A)
endothelin receptor antagonist, in spontaneoulsy hypertensive hamsters.
AB - INTRODUCTION: The purpose of this study was to determine whether prolonged oral
therapy with sitaxsentan, a potent selective ET(A) endothelin receptor
antagonist, normalizes systolic blood pressure in spontaneously hypertensive
hamsters, a new rodent model of high-renin genetic hypertension. MATERIALS AND
METHODS: Spontaneously hypertensive hamsters received either oral sitaxsentan (15
mg kg(-1) day(-1)) dissolved in high purity water or saline for 7 weeks. Systolic
blood pressure was monitored in lightly anesthetized animals using the leg-cuff
method. RESULTS: We found that sitaxsentan elicited a significant decrease in
systolic blood pressure in spontaneously hypertensive hamsters from 175 +/- 6
mmHg at baseline to 109 +/- 7 mmHg after 7 weeks (p < 0.05). Although treatment
of spontaneously hypertensive hamsters with saline was also associated with a
significant decrease in systolic blood pressure from baseline, the magnitude of
response was significantly less than that observed with sitaxsentan (p < 0.05).
DISCUSSION: Collectively, these proof-of-principle data indicate that prolonged
oral sitaxsentan therapy normalizes systolic blood pressure in spontaneously
hypertensive hamsters. We suggest that selective ET(A) endothelin receptor
blockade could be beneficial in the treatment of essential hypertension
associated with high renin plasma levels.
PMID- 17043750
TI - Codon usage and selection on proteins.
AB - Selection pressures on proteins are usually measured by comparing homologous
nucleotide sequences (Zuckerkandl and Pauling 1965). Recently we introduced a
novel method, termed volatility, to estimate selection pressures on proteins on
the basis of their synonymous codon usage (Plotkin and Dushoff 2003; Plotkin et
al. 2004). Here we provide a theoretical foundation for this approach. Under the
Fisher-Wright model, we derive the expected frequencies of synonymous codons as a
function of the strength of selection on amino acids, the mutation rate, and the
effective population size. We analyze the conditions under which we can expect to
draw inferences from biased codon usage, and we estimate the time scales required
to establish and maintain such a signal. We find that synonymous codon usage can
reliably distinguish between negative selection and neutrality only for
organisms, such as some microbes, that experience large effective population
sizes or periods of elevated mutation rates. The power of volatility to detect
positive selection is also modest--requiring approximately 100 selected sites-
but it depends less strongly on population size. We show that phenomena such as
transient hyper-mutators can improve the power of volatility to detect selection,
even when the neutral site heterozygosity is low. We also discuss several
confounding factors, neglected by the Fisher-Wright model, that may limit the
applicability of volatility in practice.
PMID- 17043752
TI - Activation dependent expression of MMPs in peripheral blood mononuclear cells
involves protein kinase A.
AB - Monocyte/Macrophages are integral cellular components of inflammation. Matrix
metalloproteinases (MMPs) produced by these cells play a crucial role in every
aspect of inflammation. Results of the investigations on activation dependent
upregulation of MMPs in human peripheral blood mononuclear cells in culture using
different lectins as an in vitro model system to mimic inflammatory monocytes are
presented. Under normal physiological conditions the monocytes produced only very
low amount of MMPs in an indomethacin insensitive PG/cAMP independent manner.
Zymographic analysis and ELISA showed that treatment of monocyte with lectins
like concanavalin A (ConA), wheat germ agglutinin (WGA) and Artocarpus lakoocha
agglutinin (ALA) caused upregulation of MMPs and the maximum effect was produced
by ALA. ALA significantly upregulated MMP-9 in a concentration and time dependent
manner. Immunoblot analysis and RT-PCR confirmed ALA mediated upregulation of MMP
9 production. Inhibition of ALA effect by indomethacin and reversal of the
indomethacin effect by Bt(2)cAMP indicated involvement of cAMP dependent
signaling pathway. Further support for the prostaglandin mediated effect was
obtained by the upregulation of cyclooxygenase by ALA. H-89, an inhibitor of
protein kinase A (PKA), inhibited the expression of MMP-9 indicating that ALA
mediated upregulation of MMP-9 is mediated through PKA pathway. Increase in MMP
production and increase in cyclooxygenase activity and inhibition of the effect
of ALA on MMP production by indomethacin suggested that the ALA activated
monocytes in culture can be used as an in vitro model system to study the
intracellular signaling process involved in the mediation of inflammatory
response.
PMID- 17043753
TI - Prohibitin suppresses renal interstitial fibroblasts proliferation and phenotypic
change induced by transforming growth factor-beta1.
AB - Prohibitin (PHB), a potential tumor suppressor, has been shown to inhibit cell
proliferation by repressing E2F-mediated transcription. But little is known about
the role of PHB involved in tubulointerstitial fibrosis (TIF). Here, for the
first time, we found PHB protein was positively expressed at normal renal
tissues, strongly down-regulated in renal biopsy specimens, and negatively
correlated with the expression of alpha-smooth-muscle actin (alpha-SMA) and with
the degrees of tubulointerstitial lesions. Transforming growth factor-beta1 (TGF
beta1) is the most important profibrotic cytokine in the process of TIF and
capable of inducing cell phenotypic change of interstitial fibroblasts
characterized by the de novo expression of alpha-SMA. Confocal microscopy showed
majority of PHB is located at cytoplasm as well as at nucleus in rat kidney
fibroblasts cell (NRK-49F). As we found that PHB protein and mRNA expression were
down-regulated in NRK-49F cells following TGF-beta1 stimulation. We used
transient transfection to over-express PHB protein and found that cells with
increased PHB levels had a significant reduction in the percentage entering cell
cycle and abolished de novo expression of alpha-SMA following TGF-beta1
stimulation. Therefore, over-expression of PHB suppresses renal interstitial
fibroblasts proliferation and cell phenotypic change induced by TGF-beta1, which
indicates PHB as a potential therapeutic target to halt the progression of TIF.
PMID- 17043754
TI - Cytological response of hemocytes in the European flat oyster, Ostrea edulis,
experimentally exposed to mercury.
AB - Molluscs bivalves have been widely used as bioindicators to monitor contamination
levels in coastal waters. In addition, many studies have attempted to analyze
bivalve organs, considered pollutant-targets, to understand the bio-accumulation
process and to characterize the effects of pollutants on the organisms. Here we
analyzed the effects of mercury exposure on flat oyster hemocytes. Optical and
electronic microscope procedures were used to characterize hemocyte morphology.
In addition, cell solutions treated with acridine orange were analyzed by flow
cytometry and laser scanning cytometry in order to evaluate the variations of
cytoplasmic granules (red fluorescence, ARF) and cell size (green fluorescence,
AGF) of hemocyte populations over time. Light and electron microscopical studies
enabled us to differentiate four hemocyte subpopulations, agranulocytes (Types I
and II) and granulocytes (Types I and II). Slight morphological differences were
observed between control and Hg-exposed cells only in granulocytes exposed to Hg
for 30 days, where condensed chromatin and partially lysed cytoplasmic regions
were detected. Flow and laser scanning cytometry studies allowed us to
differentiate three hemocyte populations, agranulocytes (R1) and granulocytes (R2
and R3). The exposure time to Hg increased the average red fluorescence (ARF) of
agranulocytes and small granulocytes, while there was no change in large
granulocytes, which showed a loss of membrane integrity. In control oysters, the
three hemocyte populations showed an increase of ARF after 19 days of exposure
although initial values were restored after 30 days. The average green
fluorescence (AGF) was more stable than the ARF throughout the experiment. In Hg
exposed oysters, the values of AGF of agranulocytes showed an increase at half Hg
exposure period while the AGF values of large granulocytes decreased throughout
the experiment, confirming the instability of these types of cells. The relative
percentage of small granulocytes and granulocytes showed time variations in both
control and exposed oysters. However, the values of small granulocytes remained
constant during the whole experiment. The fact that there were only changes in
agranulocytes and large granulocytes suggested a possible relationship between
these two types of cells. In a quantitative study, we found a significant linear
relationship between the agranulocytes and large granulocytes.
PMID- 17043755
TI - [Stenting of the SFA--indications, techniques, results].
AB - Aggressive risk factor modification, change of eating habits, exercise programs,
and forceful antiplatelet therapy are the most important tools for the treatment
of PAOD in symptomatic patients suffering from intermittent claudication. There
are however no guidelines for revascularization at this stage. Endovascular
treatment has been increasingly utilized over the last decade and increasingly
displaced vascular surgery. Amongst numerous endovascular techniques beside PTA,
stents meanwhile play the most important role due to constant technical progress.
Results regarding the rate of restenosis or patency rates still remain worse
compared to other vascular beds. This paper gives a review over recent results,
currently available stent techniques, and possible indications for the
endovascular therapy of an artery, which has turned out to be the biggest ordeal
for material and construction of stents.
PMID- 17043757
TI - Multiple intermediate conformations of jack bean urease at low pH: anion-induced
refolding.
AB - Structural and functional characteristics of jack bean urease (JBU), a hexameric
enzyme having identical subunits, were investigated under neutral as well as
acidic conditions by using CD, fluorescence, ANS binding and enzyme activity
measurements. At low pH and low ionic strength, JBU exists in a partially
unfolded state (U(A)-state), having predominantly beta structure and no tertiary
interactions along with a strong ANS binding. Addition of salts like NaCl, KCl
and Na(2)SO(4) to the U(A)-state induces refolding resulting in structural
propensities similar to that of native hexamer. Moreover, at low concentrations,
GuHCl behaves like an anion by inducing refolding of the U(A)-state. The anion
induced refolded state (I(A)-state) is more stable than U(A)-state and the
stability is nearly equal to that of the native protein against chemical-induced
and thermal denaturation. Overall, these observations support a model of protein
folding for a multimeric protein where certain conformations (ensembles of
substates) of low energy prevail and populated under non-native conditions with
different stability.
PMID- 17043758
TI - Identification and characterization of a gamma-glutamyl transpeptidase from a
thermo-alcalophile strain of Bacillus pumilus.
AB - A gamma-glutamyltranspeptidase (GGT, E.C. 2.3.2.2) was isolated from a strain
(A8) originating from Lake Bogoria (Kenya) and homologous with Bacillus pumilus.
This GGT shows an optimal activity at pH 8.9 and 62 degrees C. The enzyme is
thermostable up to 43 degrees C. The best reagent among the potential inhibitors
was shown to be DON, which is an inhibitor highly specific for GGTs. Gly-Gly-Ala,
Gly-Gly-Gly and Gly-Gly were identified as the best acceptors for the
transpeptidation reactions catalyzed by the enzyme. The SDS-PAGE study revealed
that the enzyme consists of two non-identical subunits (38,000 and 23,000). Only
the large subunit was active when the enzyme was dissociated under denaturing
conditions. The behavior of the native enzyme suggests that the active site of
the large subunit is masked by the small subunit.
PMID- 17043759
TI - Phylogenetic analysis of partial S1 and N gene sequences of infectious bronchitis
virus isolates from Italy revealed genetic diversity and recombination.
AB - A total of ten infectious bronchitis virus (IBV) isolates collected from
commercial chickens in Italy in 1999 were characterized by RT-PCR and sequencing
of the S1 and N genes. Phylogenetic analysis based on partial S1 gene sequences
showed that five field viruses clustered together with 793/B-type strains, having
91.3-98.5% nucleotide identity within the group, and one isolate had very close
sequence relationship (94.6% identity) with 624/I strain. These two IBV types
have been identified in Italy previously. The other three variant isolates formed
novel genotype detected recently in many countries of Western Europe. For one of
these variant viruses, Italy-02, which afterwards became the prototype strain,
the entire S1 gene was sequenced to confirm its originality. In contrast,
phylogenetic analysis of more conserved partial N gene sequences, comprising 1
300 nucleotides, revealed different clustering. Thus, three variant IBVs of novel
Italy-02 genotype, which had 96.7-99.2% S1 gene nucleotide identity with each
other, belonged to three separate subgroups based on N gene sequences. 624/I-type
isolate Italy-06 together with Italy-03, which was undetectable using S1 gene
primers, shared 97.7% and 99.3% identity, respectively, in N gene region with
vaccine strain H120. Only one of the 793/B-type isolates, Italy-10, clustered
with the 793/B strain sharing 99.3% partial N gene identity, whereas the other
four isolates were genetically distant from them (only 87.7-89.7% identity) and
formed separate homogenous subgroup. The results demonstrated that both mutations
and recombination events could contribute to the genetic diversity of the Italian
isolates.
PMID- 17043760
TI - Tumors in mice transgenic for the envelope protein of Jaagsiekte sheep
retrovirus.
AB - Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary
adenocarcinoma (OPA), a contagious lung cancer in sheep. Previous studies have
shown that the JSRV envelope protein (Env) functions as an oncogene, in that it
can morphologically transform rodent fibroblast and epithelial cell lines. To
obtain a small animal model for JSRV-induced OPA, we generated a transgene
expressing an epitope-tagged JSRV Env under control of the lung-specific
Surfactant Protein A (SPA) promoter. Transgenic mice containing the SPA-Env-HA
transgene showed low efficiency but specific expression in the lung. F1 male
progeny from one transgenic founder developed subdermal lipomas that expressed
the transgene. These results indicate that the JSRV Env protein is capable of
inducing tumors in transgenic mice, and in other cell types besides lung
epithelial cells.
PMID- 17043761
TI - Postmenopausal osteoporosis. What have we learned since the introduction of
bisphosphonates?
AB - Over the past 12 years bisphosphonates have become a mainstay of treatment for
postmenopausal osteoporosis. As a class, bisphosphonates significantly suppress
bone turnover and increase BMD at the lumbar spine and other site through their
direct inhibitory effects on osteoclasts. Alendronate and risedronate reduce the
incidence of clinical vertebral and non-vertebral fractures. Etidronate and both
oral and intravenous ibandronate reduce the incidence of clinical vertebral
fractures, but data from primary analyses for reduction in non-vertebral
fractures are currently less robust. Intravenous administration of zoledronate is
under late-stage investigation for use in postmenopausal osteoporosis.
Combinations of alendronate with estrogen or raloxifene provide a greater
reduction in bone turnover markers and greater increases in BMD, but fracture
risk reduction has not been determined. Overall, bisphosphonates are well
tolerated. The most common side effects of oral bisphosphonates are upper
gastrointestinal symptoms. Newer safety concerns about the use of bisphosphonates
include osteonecrosis of the jaw and oversuppression of bone turnover. The
optimal duration of bisphosphonate treatment has not been clearly established.
PMID- 17043762
TI - The use of parathyroid hormone in the treatment of osteoporosis.
AB - Anabolic skeletal agents have recently broadened our therapeutic options for
osteoporosis. By directly stimulating bone formation, they reduce fracture
incidence by improving bone qualities in addition to increasing bone mass.
Teriparatide [recombinant human parathyroid hormone(1-34)], the only anabolic
agent currently approved in the United States for osteoporosis, has emerged as a
major therapeutic approach to selected patients with osteoporosis. Teriparatide
is approved for both postmenopausal women and men with osteoporosis who are at
high risk for fracture. With the use of this anabolic agent, bone density and
bone turnover increase, microarchitecture improves, and bone size is beneficially
altered. The incidence of vertebral and nonvertebral fractures is reduced with
teriparatide use. Combination therapy with parathyroid hormone and an
antiresorptive does not appear to offer definitive advantages over the use of PTH
or an antiresorptive alone, although recent ideas about combining these agents
may offer new insights. In order to maintain increases in bone density acquired
during PTH therapy, it is important to follow its use with an antiresorptive
agent.
PMID- 17043764
TI - The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and
tumor-host interactions.
AB - Interleukin-1 (IL-1) includes a family of closely related genes; the two major
agonistic proteins, IL-1alpha and IL-1beta, are pleiotropic and affect mainly
inflammation, immunity and hemopoiesis. The IL-1Ra antagonist is a physiological
inhibitor of pre-formed IL-1. Recombinant IL-1alpha and IL-1beta bind to the same
receptors and induce the same biological functions. As such, the IL-1 molecules
have been considered identical in normal homeostasis and in disease. However, the
IL-1 molecules differ in their compartmentalization within the producing cell or
the microenvironment. Thus, IL-1beta is solely active in its secreted form,
whereas IL-1alpha is mainly active in cell-associated forms (intracellular
precursor and membrane-bound IL-1alpha) and only rarely as a secreted cytokine,
as it is secreted only in a limited manner. IL-1 is abundant at tumor sites,
where it may affect the process of carcinogenesis, tumor growth and invasiveness
and also the patterns of tumor-host interactions. Here, we review the effects of
microenvironment- and tumor cell-derived IL-1 on malignant processes in
experimental tumor models and in cancer patients. We propose that membrane
associated IL-1alpha expressed on malignant cells stimulates anti-tumor immunity,
while secretable IL-1beta, derived from the microenvironment or the malignant
cells, activates inflammation that promotes invasiveness and also induces tumor
mediated suppression. Inhibition of the function of IL-1 by the IL-1Ra, reduces
tumor invasiveness and alleviates tumor-mediated suppression, pointing to its
feasibility in cancer therapy. Differential manipulation of IL-1alpha and IL
1beta in malignant cells or in the tumor's microenvironment can open new avenues
for using IL-1 in cancer therapy.
PMID- 17043763
TI - New imaging technologies in the diagnosis of osteoporosis.
AB - In the context of osteoporosis, bone quality--which encompasses trabecular and
cortical micro-architecture, mass, and tissue mechanical & compositional
properties--plays an important and as yet undiscovered role. Non-invasive
assessment of bone quality has recently received considerable attention, as bone
density alone has not been able to predict existing or future osteoporotic
fractures, or to explain therapeutic effects of emerging treatments. The goal of
this review, therefore, is to present imaging modalities and related analysis
methods capable of assessing bone quality for improved diagnosis and care of
osteoporotic individuals. The techniques described include quantitative
ultrasound, quantitative computed tomography, peripheral quantitative tomography,
micro computed tomography, magnetic resonance, radiographic texture analysis, as
well as finite element analysis based on the above-mentioned imaging modalities.
The performance of these techniques in predicting osteoporotic fracture and
assessing strength indices are discussed.
PMID- 17043765
TI - Web portal for management of bioindication methods and ecotoxicological tests in
ecological risk assessment.
AB - The objective of this article is to inform about efforts to design and implement
a data model that can parametrically describe and store information about a wide
range of ecotoxicological tests and bioindication methods used in Ecological Risk
Assessment (EcoRA). At the same time it describes comprehensive web-based portal
built on this model that can be used to quickly find relevant biological assays
(ecotoxicological biotests) for given situation and therefore support the
decision-making process in EcoRA. The model structure, features of the
corresponding website and its current content is described in detail and proposed
development and possible collaboration is outlined. The portal (DATEST) is
located at http://projects.cba.muni.cz/datest. The aim of this work is to
complement existing EcoRA decision-support tools with a web-based engine for
storing and searching biological tests and methods used in EcoRA as there is
currently no similar informational source available on the Internet.
PMID- 17043766
TI - Signaling pathways mediating manganese-induced toxicity in human glioblastoma
cells (u87).
AB - Although essential, manganese (Mn) intake in excess leads to neurotoxicity. Mn
neurotoxicity induces impairment of energy metabolism and ultimately cell death.
Nevertheless, the signaling mechanisms underlying Mn toxicity are unknown.
Employing human glioblastoma (U87) cells, we investigated several signaling
pathways (ones promoting cellular proliferation and invasion) underlying Mn
toxicity. Mn-treatment of U87 cells induced a down-regulation of MAPK pathway but
the AKT pathway was not markedly affected. Mn-treatment of these cells induced
decreases in their levels of c-Jun and c-Fos transcription factors and
extracellular matrix degrading enzymes like MMP-2, which are associated with
glioblastoma invasiveness. Mn-treatment also induced apoptosis in U87 cells.
Thus, our results indicate that other than inducing apoptosis in U87 cells, Mn
exerts differential effects on several signaling pathways promoting glioblastoma
proliferation and invasion. Consequently, Mn may have pathophysiological roles in
inducing apoptosis and in blocking glioblastoma invasion. Our results may thus
have therapeutic implications.
PMID- 17043767
TI - Acrylamide alters cytoskeletal protein level in rat sciatic nerves.
AB - Occupational exposure and experimental intoxication with acrylamide (ACR) produce
neuropathy characterized by nerve degeneration. To investigate the mechanism of
ACR-induced neuropathy, male adult Wistar rats were given ACR (20, 40 mg/kg i.p.
3 days/week) for 8 weeks. Sciatic nerves were Triton-extracted and centrifuged at
a high speed (100,000 x g) to yield pellet and supernatant fractions. The
contents of six cytoskeletal proteins (NF-L, NF-M, NF-H, alpha-tubulin, beta
tubulin, and beta-actin) in both fractions were determined by sodium dodecyl
sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Results
showed that the three neurofilament (NF) subunits (NF-L, NF-M, NF-H) in both the
pellet and the supernatant fraction decreased significantly (P < 0.01) in the
high-dosing group, except for NF-M in the pellet. alpha-tubulin, beta-tubulin,
and beta-actin increased significantly in the supernatant (P < 0.01), whereas
both alpha-tubulin and beta-tubulin decreased significantly in the pellet (P <
0.01). However, beta-actin was not altered significantly in the sciatic nerves
pellet. These findings suggest that ACR altered the cytoskeletal protein level in
sciatic nerve, which may be one of the molecular mechanisms of ACR-induced
peripheral neuropathy.
PMID- 17043769
TI - Molecular mechanisms of GD3-induced apoptosis in U-1242 MG glioma cells.
AB - An increasing amount of evidence indicates that the disialoganglioside GD3 is
involved in apoptosis in many cell lines. Our previous studies demonstrated that
endogenous GD3 expression induced apoptosis in U-1242 MG glioma cells transfected
with the GD3 synthase gene (U1242MG-GD3 cells). In this paper, we present further
investigations on the molecular mechanisms of GD3-induced apoptosis in this cell
line. We found that endogenously synthesized GD3 localizes to the caveolae of
this cell line, where it promotes the localization of death receptor 5 (DR5),
tumor necrosis factor receptor-1 (TNF-R1), and Fas (Apo-1) to the caveolae. In
addition, caspase-8 was translocated to the caveolar fraction and cleaved; the
cleaved proteins were then re-located into the high density fractions. However,
GD3 had no effect on the distribution of the adapter protein Fas-associated death
domain (FADD). We conclude that GD3 functions as a regulatory molecule early in
the extrinsic apoptosis pathway.
PMID- 17043770
TI - Skeletal muscle translocation in vertebrates.
AB - It is now over 30 years since Bodo Christ first demonstrated that the musculature
of the limb originated from the somites and overturned the then prevailing view
that limb muscle develops from a local source. Subsequently, using electron
microscopy and histological procedures, Bodo Christ identified that cells of the
somites undergo an epithelial to mesenchymal transition which enabled them to
move from their paraxial point of origin to distal locations. These studies
defined this translocation as one of the major mechanisms allowing myogenic cells
to translocate around the body. The other means used to translocate muscle
involves the movement of cells as a sheet. The deployment of one of these two
mechanisms has been postulated to be involved in the formation of all the
hypaxial musculature of the vertebrate body. In this paper we describe the
formation of muscles both in the head and in the body, which use a translocatory
mechanism during their development. We highlight recent data showing that muscle
translocation is a far more complex process than first thought but which in
itself can be used as a valuable tool to address questions regarding tissue
patterning and development.
PMID- 17043771
TI - [Differential diagnosis of rheumatoid granuloma].
AB - Rheumatoid granuloma (RG) is histomorphologically defined as a subcutaneous
palisading granuloma with central fibrinoid necrosis. Clinically, it presents as
a nodule typically localized at pressure points near the joints. From the
rheumatic pathological point of view, the main diagnostic challenge is the
differentiation of RG from granuloma anulare, especially if clinical information
on the site of removal, known diseases, duration of illness, medication and
existing American College of Rheumatology (ACR) criteria are missing. Other
granulomatous lesions, such as mycobacterial infections, foreign body granulomas,
necrobiosis lipoidica or sarcoidosis, can be differentiated from RG by
histopathological criteria or by additional examinations such as pathogen
specification or PCR. An immunohistochemical marker for the differential
diagnosis of granulomas is not yet available. Diagnosis is based on conventional
H-E staining, alcian blue-PAS staining, polarizing analysis or PCR. In the
following article, the most important granulomatous entities in the differential
diagnosis of RG are introduced and the main diagnostic characteristics are
discussed.
PMID- 17043768
TI - NO-cGMP signaling and regenerative medicine involving stem cells.
AB - Nitric oxide (NO) is a short lived diatomic free radical species synthesized by
nitric oxide synthases (NOS). The physiological roles of NO depend on its local
concentrations as well as availability and the nature of downstream target
molecules. At low nanomolar concentrations, activation of soluble guanylyl
cyclase (sGC) is the major event initiated by NO. The resulting elevation in the
intracellular cyclic GMP (cGMP) levels serves as signals for regulating diverse
cellular and physiological processes. The participation of NO and cGMP in diverse
physiological processes is made possible through cell type specific spatio
temporal regulation of NO and cGMP synthesis and signal diversity downstream of
cGMP achieved through specific target selection. Thus cyclic GMP directly
regulates the activities of its downstream effectors such as Protein Kinase G
(PKG), Cyclic Nucleotide Gated channels (CNG) and Cyclic nucleotide
phosphodiesterases, which in turn regulate the activities of a number of proteins
that are involved in regulating diverse cellular and physiological processes.
Localization and activity of the NO-cGMP signaling pathway components are
regulated by G-protein coupled receptors, receptor and non receptor tyrosine
kinases, phosphatases and other signaling molecules. NO also serves as a powerful
paracrine factor. At micromolar concentrations, NO reacts with superoxide anion
to form reactive peroxinitrite, thereby leading to the oxidation of important
cellular proteins. Extensive research efforts over the past two decades have
shown that NO is an important modulator of axon outgrowth and guidance, synaptic
plasticity, neural precursor proliferation as well as neuronal survival.
Excessive NO production as that evoked by inflammatory signals has been
identified as one of the major causative reasons for the pathogenesis of a number
of neurodegenerative diseases such as ALS, Alzheimers and Parkinson diseases.
Regenerative therapies involving transplantation of embryonic stem cells (ES
cells) and ES cell derived lineage committed neural precursor cells have recently
shown promising results in animal models of Parkinson disease (PD). Recent
studies from our laboratory have shown that a functional NO-cGMP signaling system
is operative early during the differentiation of embryonic stem cells. The cell
type specific, spatio-temporally regulated NO-cGMP signaling pathways are well
suited for inductive signals to use them for important cell fate decision making
and lineage commitment processes. We believe that manipulating the NO-cGMP
signaling system will be an important tool for large scale generation of lineage
committed precursor cells to be used for regenerative therapies.
PMID- 17043772
TI - [Bilateral serous detachment of the neurosensory retina and retinal pigment
epithelium with rip of the peripheral pigment epithelium].
AB - HISTORY: A 52-year-old patient with atypical plasmocytoma presented with a
bilateral serous detachment of the retina as well as a huge detachment of the
pigment epithelium (PE) in the periphery. Shortly thereafter the PE ruptured. In
the left eye this led to substantial central macular fibrosis. DIAGNOSIS: The
clinically healthy patient showed a nephrotic syndrome; neither typical
monoclonality was detectable nor was erythropoiesis or myelopoiesis reduced.
THERAPY: To avoid further reduction of VA pars plana vitrectomy (ppV) with
silicone oil tamponade and laser coagulation was performed. Clinical findings
were reduced significantly and VA was stabilized for 2.5 years. DISCUSSION: PE
detachments and serous retinal detachments in patients with nephrotic syndrome
are only mentioned in a few cases. However, a peripheral rupture of the PE to
this extent seems to be very rare. Early ppV with silicone oil and laser
coagulation may prevent further macular fibrosis.
PMID- 17043773
TI - [Quality control in rehabilitation of patients with visual impairment: evaluation
of use and benefits of optic and electronic devices].
AB - BACKGROUND: Not only medical care and prescription of magnifying devices, but
also social and professional rehabilitation are part of a complete
interdisciplinary low vision service. This study provides quantitative data about
the success of rehabilitation and the quality of the Low Vision Department's
work. PATIENTS AND METHODS: A sample of 105 visually disabled patients, who had
already been provided with magnifying aids and other rehabilitation measures by
the Low Vision Department, answered a questionnaire about quality control during
a follow-up visit. The survey was carried out between May and October 2004.
Patients were asked to rate the different rehabilitation measures and to comment
on how frequently they used the different magnifying devices. Furthermore, they
were asked to judge to what degree they coped with different life situations when
using or not using the low vision aids. RESULTS: The most frequently used aids
were magnifiers (61%), glasses for near vision (34%), closed circuit television
(20%), and monocular telescopes (20%). Of the 105 patients, 85 (81%) reported on
frequent use of the devices, with just 3 patients (3%) reporting that they hardly
ever used the aids. Only 2% of the patients could read newspaper text without the
use of magnifying aids, while 51% were able to do this using the aids; 46% of the
patients reported that they had profited from the social and professional
rehabilitation measures. CONCLUSION: Independently from the causal ophthalmologic
diagnosis, patients were found to have benefited greatly from the rehabilitation
measures provided by the Low Vision Department, enabling them to take part in
more activities and participate more fully in social life, thereby greatly
improving their quality of life. Frequent use of the low vision aids by the
patient was ensured when offered alongside continued professional support.
PMID- 17043774
TI - A case of cytomegalovirus-associated multiple gastric ulcers in ulcerative
colitis.
PMID- 17043775
TI - Psychodynamic aspects of communication skills training: a pilot study.
AB - GOALS OF WORK: Communication between patients and oncology clinicians is a key
element of cancer care. Emotionally charged consultations may trigger clinicians'
defense mechanisms, protecting them from painful emotions. Defense mechanisms,
however, may also hamper the recognition of patients' suffering. This pilot study
aims to explore clinicians' defense mechanisms observed in communication skills
training (CST). PATIENTS AND METHODS: A verbatim transcription of videotaped
interviews with simulated patients were evaluated before (N=10) and after CST
(N=10) with the defense mechanism rating scales (DMRS). MAIN RESULTS: A wide
variety of defense mechanisms were observed such as obsessional (e.g.
intellectualisation) or disavowal (e.g. denial or projection). Immature defense
mechanisms decreased after CST. CONCLUSIONS: A wide variety of defense mechanisms
are operant in oncology clinicians facing challenging interviews with simulated
patients. Defense mechanisms may be modified by CST.
PMID- 17043777
TI - The expression of NK cell inhibitory receptors on cytotoxic T cells in B-cell
chronic lymphocytic leukaemia (B-CLL).
AB - Immune surveillance of tumours is mediated by cytotoxic T cells (CTL) that
recognise tumour antigen. Reduced reactivity of CTL towards tumour cells could
thus lead to disease progression and loss of tumour control. In B-cell chronic
lymphocytic leukaemia (B-CLL), the function of tumour-reactive CTL seems to
correlate inversely to disease stage. Inhibitory NK cell receptors are known to
suppress the CTL response upon interaction with major histocompatibility complex
(MHC) class I and increased expression of such receptors on CTL may inhibit the
anti-tumour response. So, the aim of this study was to investigate the expression
of NK cell inhibitory receptors on CTL in B-CLL patients and if such expression
correlated to disease stage. CD8+ T cells from B-CLL patients in Binet stage A (n
= 26) and stage C (n = 14) and healthy controls (n = 14) were analysed for the
expression of killer immunoglobulin-like receptors (KIR) CD158a (KIR2DL1), CD158b
(KIR2DL2), CD158e (KIR3DL1) and the C-type lectin receptor CD94, by flow
cytometry analysis. Patients with advanced disease (Binet stage C) had a
significantly greater percentage of CTL expressing CD158b, CD158e and CD94 than
patients with non-progressive disease (Binet stage A) and healthy controls. Stage
C patients also had a significantly higher percentage of CTL expressing CD158a
than stage A patients. No statistically significant differences were found
between Binet A patients and healthy controls. Our results suggest that increased
expression of KIR and CD94 on CTL in advanced stage B-CLL may potentially
contribute to the impaired anti-tumour immune response in these patients.
PMID- 17043778
TI - Small-bowel perforation accompanied by Aspergillus endocarditis in a patient with
angioimmunoblastic T-cell lymphoma.
PMID- 17043776
TI - Life after cancer: couples' and partners' psychological adjustment and supportive
care needs.
AB - GOALS OF WORK: Partners of cancer patients may experience significant distress at
the time of treatment and many may experience persistent difficulties, although
little research has examined their longer term psychosocial outcomes or
supportive care needs. MATERIALS AND METHODS: One hundred and fifty-four cancer
survivors who were 1-11 years post diagnosis and disease-free and their partners
completed mailed questionnaires. MAIN RESULTS: A positive relationship was found
between psychological distress and supportive care needs both within and between
partner and survivor samples. Partners reported high levels of anxiety and
supportive care needs, most frequently concerning relationships and the impact of
the cancer illness. Partners within couples reported both shared and unique
needs, although agreement on ratings of shared needs was low. Needs did not
diminish over time although partners demonstrated psychological resilience and
reported positive outcomes. Predictors of distress and unmet needs were explored:
physical QOL, relationship satisfaction, and total needs contributed to
variability in partners' distress; relationship satisfaction and total needs were
associated with survivors' distress. Distress and relationship satisfaction were
associated with partners' unmet needs; only distress was associated with
survivors' unmet needs. CONCLUSIONS: Partners are not merely providers of
support, but need support themselves many years after a cancer diagnosis and in
the context of apparently cured disease. The quality of the dyadic relationship
may be critical in determining both partner and survivor distress and needs, and
may prove a useful target for psychosocial interventions.
PMID- 17043779
TI - Association of homocysteine, vitamin B12, folic acid, and MTHFR C677T in patients
with a thrombotic event or recurrent fetal loss.
AB - Hyperhomocysteinemia (HHC) is a known risk factor for venous and arterial
thrombosis. Thrombophilia workup includes the level of homocysteine and other
related parameters such as: vitamin B(12), folic acid, and
methylenetetrahydrofolate reductase (MTHFR) C677T genotype. As the levels of
homocysteine, vitamin B(12), folic acid, and MTHFR C677T genotype are linked
biochemically, we hypothesized that a statistical association will be found
between them. The purpose of the present study was to assess the association
between the four parameters in patients with a thrombotic event or recurrent
fetal loss. The potential study population included 326 patients who were
referred to the Thrombosis and Hemostasis Unit; 125 of these patients had at
least one pathological test result of the four parameters. The correlations
between homocysteine and vitamin B(12) as well as between homocysteine and folic
acid were found to be weak (r = -0.236 and r = -0.209, respectively). No
significant difference was revealed between the mean homocysteine level and the
CC, CT, and TT MTHFR genotypes (p = 0.246). In conclusion, in the population
studied, the association between homocysteine, vitamin B(12), folic acid, and
MTHFR C677T is weak. The results raise doubt as to whether the current routine
evaluation of HHC, as part of thrombophilia workup, truly reflects the increased
risk of thrombosis.
PMID- 17043780
TI - Human mesenchymal stem cells favour healing of the cutaneous radiation syndrome
in a xenogenic transplant model.
AB - It has been suggested that human mesenchymal stem cells (hMSC) could be used to
repair numerous injured tissues. We have studied the potential use of hMSC to
limit radiation-induced skin lesions. Immunodeficient NOD/SCID mice were locally
irradiated to the leg (30 Gy, dose rate 2.7 Gy/min) using a (60)Co source to
induce a severe skin lesion. Cultured bone marrow hMSC were delivered
intravenously to the mice. The irradiated skin samples were studied for the
presence of the human cells, the severity of the lesions and the healing process.
Macroscopic analysis and histology results showed that the lesions were evolving
to a less severe degree of radiation dermatitis after hMSC transplant when
compared to irradiated non-transplanted controls. Clinical scores for the studied
skin parameters of treated mice were significantly improved. A faster healing was
observed when compared to untreated mouse. Immunohistology and polymerase chain
reaction analysis provided evidence that the human cells were found in the
irradiated area. These results suggest a possible use of hMSC for the treatment
of the early phase of the cutaneous radiation syndrome. A successful transplant
of stem cells and subsequent reduction in radiation-induced complication may open
the road to completely new strategies in cutaneous radiation syndrome therapy.
PMID- 17043781
TI - [Increased levels of auto-antibodies in thyroid diagnostics: Hashimoto
thyroidities or Graves disease?].
PMID- 17043782
TI - [Avulsion injury to the posterior horn of the lateral meniscus. Technique for
arthroscopic refixation].
AB - An avulsion of the posterior tibial insertion of the meniscus (root tear) is a
rare clinical diagnosis. Yet, due to the inconsistent clinical symptoms and the
difficult arthroscopic assessment, an injury to the root of the meniscus can be
easily missed. We present a possible technique for arthroscopic management of
root tears using a tibial tunnel approach. A possible injury mechanism could be a
rotational distortion of the knee. Another mechanism of injury is an overly
posterior tunnel placement in ACL reconstruction. The clinical assessment of the
lesion is based on thorough arthroscopic diagnosis of the lateral posterior horn
in the figure of 4 position. A tibial ACL aimer can be used to locate a K-wire in
the anatomical footprint of the posterior root of the meniscus. After
overdrilling using a 4.5-mm drill, two sutures can be passed through the meniscal
tissue and the sutures can be pulled out of the tibial tunnel. Extracortical
fixation can be used by tying the sutures over a button.A root tear of the
meniscus is a difficult clinical and arthroscopic diagnosis. A possibility for
refixation of this lesion is to use a tibial tunnel technique. An associated
injury to the ACL facilitates the tunnel placement and the suture management.
PMID- 17043784
TI - [Rotating platform spinout in LCS knee arthroplasty].
AB - In knee arthroplasty, a lax flexion gap may cause flexion instability.
Subsequently, the operated knee may subluxate or dislocate. We report on a case
of recurrent subluxations with malrotation of the rotating platform (spinout)
after primary LCS total knee arthroplasty. Potential causes for spinout, therapy
procedures, and consequences for the primary surgical technique are discussed. In
the LCS rotating platform knee arthroplasty, the flexion gap must not be laxer
than the extension gap. In such an instance, we recommend a higher rotating
platform and a more proximal distal transverse femoral osteotomy.
PMID- 17043783
TI - [Combined latissimus dorsi-thoracodorsal artery perforator-transpositional free
flap].
AB - BACKGROUND: Reconstruction or complete cover of extended but polygonal defects is
limited by the size of transplantable tissue. One of the largest composite tissue
components to be transplanted is the myocutaneous latissimus dorsi flap. Under
certain circumstances even this large-scale flap is not sufficient for complete
defect cover. Based on experiences with the thoracodorsal artery perforator (TAP)
flap, the skin island adjacent to the latissimus muscle may be raised, pedicled
on the perforator vessels penetrating the underlying muscle. Thus this island may
easily be transposed or rotated to enable additional defect cover. METHODS: This
method was applied in eight patients for defect cover at the extremities, thorax
or for hypopharynx reconstruction. The exact location of perforator vessels may
be determined pre- or intraoperatively with a hand Doppler so that skin flap
transposition can already be planned before surgery. RESULTS: All of the skin
flaps transposed or rotated healed without complications. It may even be assumed
that utilizing this method helped to avoid further complications like scar
contractures, because tension-free wound closure was feasible. CONCLUSIONS: The
combined latissimus dorsi- thoracodorsal artery perforator-transpositional free
flap is capable of covering very extensive polygonal as well as defects over
joints in order to prevent scar contractions.
PMID- 17043785
TI - [Adrenalectomy after snowboard fall. A pheochromocytoma becomes clinically
apparent in an unusual way].
AB - A 33-year-old snowboarder fell and underwent radiological examination, which was
suspicious for a vertebral body fracture. Accidentally we found a tumour of the
left suprarenal gland. Two days after the fall, he developed a hypertensive
crisis with peak blood pressure levels up to 280/120 mmHg. Further endocrinologic
testing indicated a pheochromocytoma which was confirmed by post-operative
histology. The fall is supposed to have activated the pheochromocytoma. The
course of examinations and significance of the tumour are described.
PMID- 17043786
TI - [Spinal epidural empyema. Limited surgical treatment combined with continuous
irrigation and drainage].
AB - Epidural empyema of the spinal column is a rare, but in some cases devastating,
disease. Surgery can be excessive or very limited. We want to report our results
of combined therapy of limited surgical treatment and continuous irrigation with
antibiotic solution and drainage. In the last 5 years we have operated on 12
patients (7 female, 5 male, median age: 61.5 years, range: 22-89 years) with
spinal epidural empyema. All surviving patients were evaluated after 3 months
including MRI. Six infections were caused by injections, two by spontaneous
discitis, two by chronic systemic infections, and in two patients the cause
remained unknown. In every case we implanted two catheters, one for irrigation
with antibiotic solution and one for drainage. On average the catheters were used
for 3 days. For evacuation in seven patients interlaminar fenestration in one,
two, or three levels was enough. Only in one patient was a laminectomy performed.
Five patients recovered totally, three partially, one did not recover at all, and
three died. The autopsy of two dead patients showed complete healing of the
operated area; they died because of lethal infections in other parts of their
body. In only one case did a reoperation have to be done. The cause was an
additional subdural empyema. In spite of the limited surgical procedure without
relevant operative morbidity the reported method is an effective and safe
therapy.
PMID- 17043787
TI - [Autologous chondrocyte transplantation by the sandwich technique. A salvage
procedure for osteochondritis dissecans of the knee].
AB - The case presented is that of a 23-year-old man suffering from osteochonditis
dissecans (OCD) of the medial femoral condyle, in whom a free piece of cartilage
had separated off and there was a large osteochondral defect despite numerous
operations. After refixation of the fragment failed, an autologous chondrocyte
transplantation (ACT) was performed using the sandwich technique. Three years
after the operation the patient is very satisfied with the result. The
radiological findings show stable repair of the bony and cartilaginous defect
area. This case report shows that ACT is a valid method for the treatment of
large osteochondral defects even after several previous failed operations. The
low donor site morbidity is an important advantage over other methods, such as
transplantation of osteochondral plugs.
PMID- 17043788
TI - [Defect of the femoral condyle in the knee after patellectomy. Long-term results
of fresh massive osteochondral allografting].
AB - The presence of a massive full-thickness osteochondral defect in the knee of
young and active individuals is an unsolved problem in orthopedic surgery,
especially in post-traumatic large bone defects. Fresh massive osteochondral
allografts have been used for many years but mostly in oncology but not in post
traumatic cases. This case report describes a 20-year-old right leg-dominant
woman, who, at age 19, sustained open Gustilo-Anderson type III comminuted
fractures of the left patella and lateral femoral condyle in a motorbike
accident. Initial treatment included immediate debridement and patellectomy with
lavage. The large defect of the femoral condyle was reconstructed with a massive
osteochondral allograft 1 year after the injury. The graft was obtained from our
institutional tissue bank. The damaged bearing part of the condyle was resected
to bleeding bone to create the nearly rectangular defect. The central condyle
wall remained intact. The graft was trimmed to fit the defect and fixed with
three cancellous 6.5-mm screws. The meniscus was not damaged. Partial weight
bearing was permitted at 8 weeks and full weight bearing at 16 weeks after the
surgery. At the last follow-up control 10 years after the surgery, no evidence of
tibiofemoral arthrosis was present. The allograft-host interface was not visible.
The radiodensity of the graft was nearly identical to the host bone. The Lysholm
score and clinical findings were identical (100 points) to those 18 months after
the surgery. The patient was extremely satisfied without complaints at 30 years
of age.
PMID- 17043789
TI - [Is use of the fixateur externe no longer indicated for the treatment of unstable
radial fracture in the elderly?].
AB - BACKGROUND: In recent years there has been an increasingly marked shift in the
operative treatment of unstable fractures of the distal radius. The introduction
of locking compression plates has made it possible to extend the indications for
palmar stabilisation according to the principles of internal fixation to
extension fractures even in osteoporotic bone, and since then the new design has
been used more and more widely. First clinical results show very good and good
clinical and radiological outcomes in over 80% of cases after locking compression
plate osteosynthesis. All this raises the question of whether external fixation
is no longer indicated for distal radius fractures in the elderly, or is now no
more than a second-line treatment. PATIENTS AND METHODS: Within a 5-year period,
67 patients over 65 years of age were identified among 220 who had had unstable
fractures of the distal radius in our hospital with external fixation. The
average follow-up period (clinical and radiological examinations) was 37 months.
We devoted particular attention to the analysis of complications and problems
during the treatment. RESULTS: Complete bone healing was observed in all patients
treated with external fixation. In most cases, complications were minor pin-track
infections (10%). The radiological follow-up examination revealed radial
shortening by an average of 2 mm and an average radial shift of 0.2 mm. The joint
angle was 2.5 degrees with lateral irradiation and 18 degrees with dorso-palmar
irradiation. According to the Gartland and Werley score, the functional,
radiological and subjective outcome was excellent or good in 87% of these
patients. CONCLUSIONS: Overall, internal fixation with angular fixed plates has
definite benefits. The medium- and long-term follow-up and functional outcome
still show no benefits over external fixation, however. External fixation is a
genuine option, even if as second-line treatment.
PMID- 17043790
TI - [Flexor tendon rupture after palmar osteosynthesis using a multidirectional fixed
angle plate].
AB - Six months after the internal fixation of a distal intra-articular fracture of
the radius with a fixed-angle plate (APTUS by Medartis), a 79 year old woman
sustained chronic tears in flexor digitorum profundus tendons II, III and the
flexor pollicis longus tendon.
PMID- 17043791
TI - Heterogeneity of dendritic cells in rat apical periodontitis.
AB - Dendritic cells are important for the induction of T-lymphocyte-mediated immunity
by acting as antigen-presenting cells. We have previously reported that dendritic
cells are prevalent in the chronic non-expanding phase of rat apical
periodontitis. To characterize these cells further, immunoelectron microscopy
with three dendritic cell markers (CD11c, OX6, OX62) was conducted for samples
from rat models of apical periodontitis. Dendritic cells were divided into two
types (type I or type II). Most of the type I dendritic cells expressed CD11c,
showed an irregular large profile, had typical cytoplasmic processes, and were
recognized as the major dendritic cell population. Most of the type II dendritic
cells expressed OX62, showed oval small profiles with a few thin short processes,
and were sometimes observed infiltrating from blood vessels. Cell-to-cell
contacts between type I dendritic cells and lymphocytes were the most frequently
observed associations. These results suggest that dendritic cells are composed of
heterogeneous populations that exhibit different phenotypes, morphologies, and
maturation/differentiation/activation.
PMID- 17043792
TI - Dermal matrix proteins initiate re-epithelialization but are not sufficient for
coordinated epidermal outgrowth in a new fish skin culture model.
AB - We have established a new culture system to study re-epithelialization during
fish epidermal wound healing. In this culture system, fetal bovine serum (FBS)
stimulates the epidermal outgrowth of multi-cellular layers from scale skin
mounted on a coverslip, even when cell proliferation is blocked. The rate of
outgrowth is about 0.4 mm/h, and at 3 h after incubation, the area occupied by
the epidermal sheet is nine times larger than the area of the original scale
skin. Cells at the bottom of the outgrowth show a migratory phenotype with
lamellipodia, and "purse string"-like actin bundles have been found over the
leading-edge cells with polarized lamellipodia. In the superficial cells, re
development of adherens junctions and microridges has been detected, together
with the appearance and translocation of phosphorylated p38 MAPK into nuclear
areas. Thus, this culture system provides an excellent model to study the
mechanisms of epidermal outgrowth accompanied by migration and re
differentiation. We have also examined the role of extracellular matrix proteins
in the outgrowth. Type I collagen or fibronectin stimulates moderate outgrowth in
the absence of FBS, but development of microridges and the distribution of
phosphorylated p38 MAPK are attenuated in the superficial cells. In addition, the
leading-edge cells do not have apparent "purse string"-like actin bundles. The
outgrowth stimulated by FBS is inhibited by laminin. These results suggest that
dermal substrates such as type I collagen and fibronectin are able to initiate
epidermal outgrowth but require other factors to enhance such outgrowth, together
with coordinated alterations in cellular phenotype.
PMID- 17043794
TI - Regeneration in Macrostomum lignano (Platyhelminthes): cellular dynamics in the
neoblast stem cell system.
AB - Neoblasts are potentially totipotent stem cells and the only proliferating cells
in adult Platyhelminthes. We have examined the cellular dynamics of neoblasts
during the posterior regeneration of Macrostomum lignano. Double-labeling of
neoblasts with bromodeoxyuridine and the anti-phospho histone H3 mitosis marker
has revealed a complex cellular response in the first 48 h after amputation; this
response is different from that known to occur during regeneration in triclad
platyhelminths and in starvation/feeding experiments in M. lignano. Mitotic
activity is reduced during the first 8 h of regeneration but, at 48 h after
amputation, reaches almost twice the value of control animals. The total number
of S-phase cells significantly increases after 1 day of regeneration. A
subpopulation of fast-cycling neoblasts surprisingly shows the same dynamics
during regeneration as those in control animals. Wound healing and regeneration
are accompanied by the formation of a distinct blastema. These results present
new insights, at the cellular level, into the early regeneration of
rhabditophoran Platyhelminthes.
PMID- 17043793
TI - Distribution of phosphorylated protein kinase C alpha in goldfish retinal bipolar
synaptic terminals: control by state of adaptation and pharmacological treatment.
AB - Protein kinase C (PKC) is a signalling enzyme critically involved in many aspects
of synaptic plasticity. In cyprinid retinae, the PKC alpha isoform is localized
in a subpopulation of depolarizing bipolar cells that show adaptation-related
morphological changes of their axon terminals. We have studied the subcellular
localization of phosphorylated PKC alpha (pPKC alpha) in retinae under various
conditions by immunohistochemistry with a phosphospecific antibody. In dark
adapted retinae, pPKC alpha immunoreactivity is weak in the cytoplasm of synaptic
terminals, labelling being predominantly associated with the membrane
compartment. In light-adapted cells, immunoreactivity is diffusely distributed
throughout the terminal. Western blot analysis has revealed a reduction of pPKC
alpha immunoreactivity in cytosolic fractions of homogenized dark-adapted retinae
compared with light-adapted retinae. Pharmacological experiments with the isoform
specific PKC blocker Goe6976 have shown that inhibition of the enzyme influences
immunolabelling for pPKC alpha, mimicking the effects of light on the subcellular
distribution of immunoreactivity. Our findings suggest that the state of
adaptation modifies the subcellular localization of a signalling molecule (PKC
alpha) at the ribbon-type synaptic complex. We propose that changes in the
subcellular distribution of PKC alpha immunoreactivity might be one component
regulating the strength of the signal transfer of the bipolar cell terminal.
PMID- 17043795
TI - Expression of HMGB1 during tooth development.
AB - High mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that can act
as a transcription factor, a growth factor, or a cytokine. To elucidate a
possible role for HMGB1 in tooth development, we have studied the expression of
HMGB1 and its receptor RAGE (receptor for advanced glycation end-products) during
the late fetal and early postnatal period of rat by using light- and electron
microscopic immunohistochemistry. Low HMGB1 protein expression was observed
during fetal and newborn stages of tooth development. However, from postnatal day
5 (P5) onward, a marked increase occurred in the levels of the protein in most
dental cell types. Expression was particularly high in ameloblasts and
odontoblasts at regions of ongoing mineralization. Although most HMGB1
immunoreactivity was confined to cell nuclei, it was also present in odontoblast
cytoplasm. At P5, ameloblasts and odontoblasts also showed RAGE immunoreactivity,
and reverse transcription-polymerase chain reaction demonstrated both HMGB1 and
RAGE mRNA in human dental pulp cells in vitro. Immunoblots performed on extracts
from bovine dentin demonstrated a principal band at approximately 27 kDa,
indicating that HMGB1 participates in tooth mineralization. The expression of
both ligand and receptor suggests an autocrine/paracrine HMGB1 signalling axis in
odontoblasts.
PMID- 17043796
TI - Fluorescence characterization of metal ion-humic acid interactions in soils
amended with composted municipal solid wastes.
AB - Fluorescence spectroscopy has been used to probe the structural properties and
Cu(II), Zn(II), Cd(II), and Pb(II)-binding behavior of humic acid (HA)-like
fractions isolated from a municipal solid waste compost (MSWC) and HAs from
unamended and MSWC-amended soils. The main feature of the fluorescence spectra,
in the form of emission-excitation matrix (EEM) plots, was a broad peak with the
maximum centered at an excitation/emission wavelength pair that was much shorter
(340/437 nm) for MSWC-HA than for unamended and MSWC-amended soil HAs (455/513
and 455/512 nm, respectively). Fluorescence intensity for MSWC-amended soil HA
was less than that for unamended soil HA. These results were indicative of more
aromatic ring polycondensation and humification of soil HAs, and of partial
incorporation of simple and low-humified components of MSWC-HA into native soil
HA, as a result of MSWC amendment. Titrations of HAs with Cu(II), Zn(II), Cd(II),
and Pb(II) ions at pH 6 and ionic strength 0.1 mol L(-1) resulted in a marked
decrease of the fluorescence intensities of untreated HAs. By successfully
fitting a single-site fluorescence-quenching model to titration data, the metal
ion complexing capacities of each HA and the stability constants of metal ion-HA
complexes were obtained. The binding capacities and stability constants of MSWC
HA were smaller than those of the unamended soil HA. Application of MSWC to soil
slightly reduced the metal-ion-binding capacities and affinities of soil HAs.
PMID- 17043798
TI - FTIR and Raman microspectroscopy of normal, benign, and malignant formalin-fixed
ovarian tissues.
AB - Ovarian cancer is the sixth most common cancer among women worldwide, and
mortality rates from this cancer are higher than for other gynecological cancers.
This is attributed to a lack of reliable screening methods and the inadequacy of
treatment modalities for the advanced stages of the disease. FTIR and Raman
spectroscopic studies of formalin-fixed normal, benign, and malignant ovarian
tissues have been undertaken in order to investigate and attempt to understand
the underlying biochemical changes associated with the disease, and to explore
the feasibility of discriminating between these different tissue types. Raman
spectra of normal tissues indicate the dominance of proteins and lower contents
of DNA and lipids compared to malignant tissues. Among the pathological tissues
studied, spectra from benign tissues seem to contain more proteins and less DNA
and lipids compared to malignant tissue spectra. FTIR studies corroborate these
findings. FTIR and Raman spectra of both normal and benign tissues showed more
similarities than those of malignant tissues. Cluster analysis of first
derivative Raman spectra in the 700-1700 cm(-1) range gave two clear groups, one
corresponding to malignant and the other to normal+benign tissues. At a lower
heterogeneity level, the normal+benign cluster gave three nonoverlapping
subclusters, one corresponding to normal and two for benign tissues. Cluster
analysis of second-derivative FTIR spectra in the combined spectral regions of
1540-1680 and 1720-1780 cm(-1) resulted into two clear clusters corresponding to
malignant and normal+benign tissues. The cluster corresponding to normal+benign
tissues produced nonoverlapping subclusters for normal and benign tissues at a
lower heterogeneity level. The findings of this study demonstrate the feasibility
of Raman and FTIR microspectroscopic discrimination of formalin-fixed normal,
benign, and malignant ovarian tissues.
PMID- 17043797
TI - Analysis of type I and IV collagens by FT-IR spectroscopy and imaging for a
molecular investigation of skeletal muscle connective tissue.
AB - Many muscular diseases result from abnormal organization of connective tissue
and/or collagen network formation. Only a few molecular imaging techniques are
able to analyze this collagen network by differentiating collagen types. In this
study, FT-IR spectroscopy was used to analyze type I and IV collagens, the most
important compounds of which are perimysium and endomysium, respectively.
Secondary structure of collagen types was determined by curve-fitting the 1,700
1,480 cm(-1) spectral interval. Type I collagen could be differentiated from type
IV by its higher amounts of triple helix and alpha-helix, but lower amounts of
beta-sheets (P < 0.01). FT-IR imaging was then used to determine structural
features of perimysium and endomysium collagen network in bovine Flexor carpi
radialis muscle. Secondary structure of proteins contained in perimysium and
endomysium was found to be very close to type I and IV collagens, respectively.
FT-IR spectroscopy and imaging are thus analytical tools that might be used for
investigating biodistribution and assembly of collagen types in connective
tissues.
PMID- 17043799
TI - Differential proteome analysis of colon carcinoma cell line SW480 after
reconstitution of the tumour suppressor Smad4.
AB - The tumour suppressor gene Smad4 is frequently inactivated in gastrointestinal
carcinomas. Smad4 plays a pivotal role in transducing signals of the transforming
growth factor-beta (TGF-beta) superfamily of proteins. Inactivation of Smad4
seems to occur late during tumour progression when tumours acquire invasive and
metastatic properties. Identification of proteins directly or indirectly
regulated by Smad4 would, therefore, ease the future design of new diagnostic and
therapeutic strategies for gastrointestinal carcinoma. We have used human colon
carcinoma cell line SW480 stably transfected with Smad4 as an in-vitro model
system to identify Smad4-regulated proteins by applying two-dimensional gel
electrophoresis (2DE) then MALDI-PMF/PFF-MS. We identified a total of 47 protein
species with a Smad4-dependent expression. From the functions of the candidate
proteins we obtained new insights into Smad4's participation in processes, for
example apoptosis, differentiation, and proliferation.
PMID- 17043800
TI - Increased gene expression of scavenger receptors and proinflammatory markers in
peripheral blood mononuclear cells of hyperlipidemic males.
AB - Interactions between peripheral blood mononuclear cells (PBMCs) and those within
plaques are suggested to be pathophysiologically relevant to lipid-induced
arteriosclerosis. In this study, gene expressions of scavenger receptors (CD36,
CD68), LPS receptor (CD14), proinflammatory (tumor necrosis factor alpha
[TNFalpha], CD40, interleukin-1 beta [IL-1beta]) and oxidative stress-related
(manganese superoxide dismutase [MnSOD]) markers were analyzed in PBMCs of
clinically asymptomatic males with classical proatherogenic risk factors such as
smoking and/or hyperlipidemia. PBMCs were isolated from venous blood of
normolipidemic non-smokers (n = 10) and smokers (n = 8), and hyperlipidemic non
smokers (n = 9) and smokers (n = 8). RNA from PBMCs was used for PCR analyses.
Plasma concentrations of oxidized low-density lipoproteins (oxLDL) were measured
by ELISA. The gene expressions of CD36, CD68, CD40, TNFalpha, and MnSOD were
significantly higher in PBMCs of hyperlipidemics than in normolipidemics,
irrespective of whether they were smoking or not. The individual expression of
these genes showed significant positive correlations with each other but also
with serum cholesterol or plasma oxLDL concentrations. The higher expressions of
scavenger receptors, proinflammatory and oxidative stress-related genes of PBMCs
are suggested to result mainly from hyperlipidemia and the accompanied increase
of oxLDL concentrations.
PMID- 17043801
TI - Inhibitory effects of a specific phage-displayed peptide on high peritoneal
metastasis of gastric cancer.
AB - Peritoneal dissemination in gastric cancer is the most frequent cause of the
noncurative resection and recurrence after curative resection. We, therefore,
evaluated the feasibility of a peptide, which was obtained by screening a random
phage display library, in the treatment of peritoneal metastases of gastric
cancer. In this study, a novel cell line, GC9811-P, with a high potential
peritoneal metastasis of gastric cancer derived from its parental cell line,
GC9811, was established. Using a phage display library, we isolated a specific
peptide that selectively bound to GC9811-P cells rather than its parental
GC9811cells. The isolated phage-displaying peptide, SMSIASPYIALE (named peptide
PIII), was obtained after four rounds of selection, showing a tendency to
preferentially bind to GC9811-P cells compared with a panel of other gastric
cancer cell lines, and preferentially accumulate in peritoneal metastasis tumor
tissue in comparison with control organs, peritoneum, liver, pancreas, spleen,
lung, and kidney. Further study showed that synthetic peptide PIII could
significantly inhibit adhesive and invasional ability of GC9811-P cells and could
effectively block the corresponding phage binding to the GC9811-P cells, whereas,
exposure of the cells to various concentrations of peptide PIII showed no obvious
cell growth inhibition. Furthermore, a highly reproducible animal experimental
model of gastric cancer with peritoneal dissemination was established in nude
mice by injecting a suspension of the cell line into the gastric wall of nude
mice. Animals intraperitoneally treated with peptide PIII in this model or
another animal model of gastric cancer with peritoneal dissemination established
using MKN45 cells showed suppressed tumor metastasis to peritoneum and
significantly prolonged survival. In conclusion, the selected peptide PIII was a
biologically active peptide and could effectively inhibit peritoneal
dissemination of gastric cancer.